Journal articles: '728.6 (469.112)' – Grafiati (2024)

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Fusarium oxysporum Schechtend.:Fr. f. sp. phaseoli J. B. Kendrick & W. C. Snyder (FOP) is the causal agent of the common bean (Phaseolus vulgaris L.) disease known as Fusarium wilt or Fusarium yellows. FOP has been reported from the Castilla y Leon region in Spain, where it is a serious problem on most commercial bean cultivars (1). Five FOP isolates from Spain (AB-6, AB-111, AB-112, AS-1, and AS-4) obtained from J. M. Díaz-Mínguez and the isolate FOP-CO1 (ATCC 90245) from Colorado were tested for pathogenicity on two American lines: Pinto U.I. 114, considered as a universal susceptible check, and Flor de Mayo, a Mexican landrace. Seedlings were root-clip inoculated and evaluated according to the CIAT 1 to 9 severity scale, in which 1 to 3 = resistant, 3.1 to 6 = intermediate, and 6.1 to 9 = susceptible. Three inoculum concentrations were tested: 104, 105, and 106 conidia/ml. AS-1 and AS-4 produced resistant reactions in both U.I. 114 (1.5 to 2.1 and 1.2 to 1.5) and Flor de Mayo (1.9 to 2.3 and 1.4), respectively, at all inoculum concentrations. Susceptible reactions to AB-6 (7.3 to 8.9), AB-111 (7.6 to 8.9), AB-112 (7.5 to 7.9), and FOP-CO1 (8.1 to 8.6) were observed in Pinto U.I. 114, regardless of inoculum concentration, although severity ratings increased as the inoculum concentration was increased. Flor de Mayo exhibited a susceptible reaction (6.7 to 7.8) to FOP-CO1 at all inoculum concentrations tested, and intermediate reactions to AB-6 (4.9), AB-111 (5.4), and AB-112 (5.0) at the lowest inoculum concentration. Susceptible reactions (7 to 8.2 for AB-6; 6.8 to 7.0 for AB-111, and 7.3 to 7.7 for AB-112) occurred with higher inoculum concentrations, and severity ratings increased as the inoculum concentration increased. Recently, FOP isolates from Greece and Italy were recognized as each belonging to different pathogenic races (2); consequently, more research on the Spanish isolates (AB-6, AB-111, and AB-112) is needed to determine if they are similar to the races reported from the Mediterranean Basin or should be classified as a new FOP race (s). References: (1) J. M. Díaz-Mínguez et al. Plant Dis. 80:600, 1996. (2) S. L. Woo et al. Phytopathology 86:966, 1996.

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Aims/Objectives/BackgroundGlobally, injuries cause more than 5 million deaths annually. Children and young people are a particularly vulnerable group and injuries are the leading cause of death in people aged 5–24 years globally and a leading cause of disability.In most low and middle-income countries where the majority of global child injury burden occurs, systems for routinely collecting injury data are limited. There is a continuing need for better data on childhood injuries and for injury surveillance.The aim of our study was to introduce a hospital-based injury surveillance tool – the first of its kind in Nepal and explore its feasibility. We undertook prospective collection of data on all injuries/trauma presenting to 2 hospital emergency departments to describe the epidemiology of paediatric hospital injury presentations and associated risk factors.Methods/DesignA new injury surveillance system for use in emergency departments in Nepal was designed and used to collect data on patients presenting with injuries. Data were collected prospectively in two hospitals 24 h a day over 12 months (April 2019 - March 2020) by trained data collectors using tablet computers.Abstract 432 Table 1Socio-demographic profile and characteristics of injury among children attending emergency of hospitals in Makwanpur district, Nepal, April 2019 – March 2020 (N=2696)CharacteristicsFrequencyGender Male 1778 Female 918 Age groups 0–4 years 653 5–9 years 866 10–14 years 680 15–17 years 497 Median year (IRQ) 8 (5 – 13) Ethnicity/caste Janajati 1384 Brahmin/Chhetri 892 Dalit 148 Madhesi 146 Muslim 74 Others 50 Unknown 2 Place where injury occurred Home/Compound 1576 Highway/road/street 636 School 233 Recreational area 138 Workplace 76 Other 37 Activities at the time injury occurred Leisure/Play 1889 Travelling (other than to/from school/work) 296 Work 202 Travelling (to/from school/work) 184 Education 42 Organised sports 11 Other 52 Unknown 20 Intent of injury Unintentional 2560 Intentional (self-harm) 61 Intentional (assault) 75 Unintentional (n=2560) Fall 912 Animal or insect related 728 Road traffic injury 356 Injured by a blunt force 201 Stabbed, cut or pierced 176 Fire, burn or scald 65 Poisoning 52 Suffocation/choking 36 Electrocution 12 Drowning and submersion 7 Other 13 Unknown 2 Self-harm (n=61) Poisoning 38 Hanging, strangulation, suffocation 12 Stabbed, cut or pierced 6 Injured by blunt object 4 Other 1 Assault (n=75) Bodily force (physical violence) 43 Injured by blunt object 18 Stabbed, cut or pierced 8 Pushing from a high place 2 Poisoning 2 Sexual assault 1 Other 1 Nature of injury (one most severe) Cuts, bites or open wound 1378 Bruise or superficial injury 383 Fracture 299 Sprain, strain or dislocation 243 Internal injury 124 Head Injury/Concussion 83 Burns 67 Other 115 Unknown 2 Not recorded 2 Severity of injury No apparent injury 125 Minor 1645 Moderate 813 Severe 111 Not recorded 2 Disposition Discharged 2317 Admitted to hospital 164 Transferred to another hospital 179 Died 21 Leave Against Medical Advice (LAMA) 11 Unknown 2 Not recorded 2 Note:Not recorded = missing cases95% CI calculated using one proportion test and normal approximation method in Minitab.Abstract 432 Table 2Distribution of injuries by age-group, sex and mechanism of injury among children attending emergency of hospitals in Makwanpur district, Nepal, April 2019 – March 2020Age groups & Sex0 - 4 years5 - 9 years10–14 years15–17 yearsMaleFemaleTotalIntent & mechanismsn (%)n (%)n (%)n (%)n (%)n (%)n (%)Unintentional Fall 239 (26.2) 328 (36.0) 249 (27.3) 96 (10.5) 636 (69.7) 276 (30.3) 912 (100) Animal or insect related 175 (24.0) 260 (35.7) 190 (26.1) 103 (14.1) 470 (64.6) 258 (35.4) 728 (100) Road traffic injury 49 (13.8) 108 (30.3) 86 (24.2) 113 (31.7) 223 (62.6) 133 (37.4) 356 (100) Injured by a blunt force 54 (26.9) 74 (36.8) 49 (24.4) 24 (11.9) 150 (74.6) 51 (25.4) 201 (100) Stabbed, cut or pierced 20 (11.4) 56 (31.8) 49 (27.8) 51 (29.0) 127 (72.2) 49 (27.8) 176 (100) Fire, burn or scald 42 (64.6) 10 (15.4) 9 (13.8) 4 (6.2) 27 (41.5) 38 (58.5) 65 (100) Poisoning 33 (63.5) 6 (11.5) 5 (9.6) 8 (15.4) 26 (50.0) 26 (50.0) 52 (100) Suffocation/choking 24 (66.7) 5 (13.9) 2 (5.6) 5 (13.9) 20 (55.6) 16 (44.4) 36 (100) Electrocution 2 (15.7) 0 (0.0) 3 (25.0) 7 (58.3) 10 (83.3) 2 (16.7) 12 (100) Drowning and submersion 1 (14.3) 1 (14.3) 3 (42.9) 2 (28.6) 3 (42.9) 4 (57.1) 7 (100) Other 6 (46.2) 4 (30.8) 3 (23.1) 0 (0.0) 10 (76.9) 3 (23.1) 13 (100) Unknown 2 (100) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 2 (100) 2 (100) Total 647 (25.3) 852 (33.3) 648 (25.3) 413 (16.1) 1702 (66.5) 858 (33.5) 2560 (100) Self-harm Poisoning 0 (0.0) 0 (0.0) 6 (15.8) 32 (84.2) 7 (18.4) 31 (81.6) 38 (100) Hanging 0 (0.0) 0 (0.0) 3 (25.0) 9 (75.0) 4 (33.3) 8 (66.7) 12 (100) Stabbed, cut or pierced 0 (0.0) 0 (0.0) 2 (33.3) 4 (66.7) 1 (16.7) 5 (83.3) 6 (100) Injured by blunt object 0 (0.0) 2 (50.0) 2 (50.0) 0 (0.0) 4 (100) 0 (0.0) 4 (100) Other 0 (0.0) 0 (0.0) 0 (0.0) 1 (100) 1 (100) 0 (0.0) 1 (100) Total 0 (0.0) 2 (3.3) 13 (21.3) 46 (75.4) 17 (27.9) 44 (72.1) 61 (100) Assault Bodily force (physical violence) 3 (7.0) 1 (2.3) 11 (25.6) 28 (65.1) 37 (86.0) 6 (14.0) 43 (100) Injured by blunt object 2 (11.1) 8 (44.4) 4 (22.2) 4 (22.2) 13 (72.2) 5 (27.8) 18 (100) Stabbed, cut or pierced 1 (12.5) 0 (0.0) 2 (25.0) 5 (62.5) 7 (87.5) 1 (12.5) 8 (100) Pushing from a high place 0 (0.0) 1 (50.0) 1 (50.0) 0 (0.0) 1 (50.0) 1 (50.0) 2 (100) Poisoning 0 (0.0) 1 (50.0) 0 (0.0) 1 (50.0) 1 (50.0) 1 (50.0) 2 (100) Sexual assault 0 (0.0) 0 (0.0) 1 (100) 0 (0.0) 0 (0.0) 1 (100) 1 (100) Other 0 (0.0) 1 (100) 0 (0.0) 0 (0.0) 0 (0.0) 1 (100) 1 (100) Total 6 (8.0) 12 (16.0) 19 (25.3) 38 (50.7) 59 (78.7) 16 (21.3) 75 (100) Abstract 432 Table 3Association of injury location, nature and severity with age among children attending emergency of hospitals in Makwanpur district, Nepal, April 2019 – March 2020Age groups0 – 4 years5 – 9 years10–14 years15–17 yearsTotalChi-SquareInjury characteristicsn (%)n (%)n (%)n (%)n (%)P valueLocation of injury sustained Home/Compound 537 (34.1) 504 (32.0) 319 (20.2) 216 (13.7) 1576 (100) <0.001 Highway/road/street 85 (13.4) 196 (30.8) 190 (29.9) 165 (25.9) 636 (100) School 15 (6.4) 107 (45.9) 85 (36.5) 26 (11.2) 233 (100) Recreational area 9 (6.5) 44 (31.9) 55 (39.9) 30 (21.7) 138 (100) Workplace 1 (1.3) 4 (5.3) 19 (25.0) 52 (68.4) 76 (100) Other 6 (16.2) 11 (29.7) 12 (32.4) 8 (21.6) 37 (100) Total 653 (24.2) 866 (32.1) 680 (25.2) 497 (18.4) 2696 (100) Nature of injury Cuts, bites or open wound 328 (23.8) 506 (36.7) 314 (22.8) 230 (16.7) 1378 (100) <0.001 Bruise or superficial injury 81 (21.1) 99 (25.8) 118 (30.8) 85 (22.2) 383 (100) Fracture 48 (16.1) 101 (33.8) 112 (37.5) 38 (12.7) 299 (100) Sprain, strain or dislocation 48 (19.8) 78 (32.1) 72 (29.6) 45 (18.5) 243 (100) Internal injury 44 (35.5) 8 (6.5) 18 (14.5) 54 (43.5) 124 (100) Head Injury/Concussion 18 (21.7) 26 (31.3) 18 (21.7) 21 (25.3) 83 (100) Burns 42 (62.7) 9 (13.4) 10 (14.9) 6 (9.0) 67 (100) Other 41 (35.7) 38 (33.0) 18 (15.7) 18 (15.7) 115 (100) Unknown 2 (100) 0 (0.0) 0 (0.0) 0 (0.0) 2 (100) Total 652 (24.2) 865 (32.1) 680 (25.2) 497 (18.4) 2694 (100) Severity of injury No apparent injury 39 (31.2) 45 (36.0) 26 (20.8) 15 (12.0) 125 (100) <0.001 Minor 419 (25.5) 535 (32.5) 406 (24.7) 285 (17.3) 1645 (100) Moderate 171 (21.0) 262 (32.2) 225 (27.7) 155 (19.1) 813 (100) Severe 23 (20.7) 23 (20.7) 23 (20.7) 42 (37.8) 111 (100) Total 652 (24.2) 865 (32.1) 680 (25.2) 497 (18.4) 2694 (100) Abstract 432 Table 4Association of injury location, nature and severity with sex among children attending emergency of hospitals in Makwanpur district, Nepal, April 2019 – March 2020SexMaleFemaleTotalChi-SquareInjury characteristicsn (%)n (%)n (%)P valueLocation of injury sustained Home/Compound 979 (62.1) 597 (37.9) 1576 (100) <0.001 Highway/road/street 421 (66.2) 215 (33.8) 636 (100) School 176 (75.5) 57 (24.5) 233 (100) Recreational area 111 (80.4) 27 (19.6) 138 (100) Workplace 62 (81.6) 14 (18.4) 76 (100) Other 29 (78.4) 8 (21.6) 37 (100) Total 1778 (65.9) 918 (34.1) 2696 (100) Nature of injury Cuts, bites or open wound 959 (69.6) 419 (30.4) 1378 (100) <0.001 Bruise or superficial injury 246 (64.2) 137 (35.8) 383 (100) Fracture 200 (66.9) 99 (33.1) 299 (100) Sprain, strain or dislocation 154 (63.4) 89 (36.6) 243 (100) Internal injury 50 (40.3) 74 (59.7) 124 (100) Head Injury/Concussion 59 (71.1) 24 (28.9) 83 (100) Burns 27 (40.3) 40 (59.7) 67 (100) Other 79 (68.7) 36 (31.3) 115 (100) Unknown 2 (100) 0 (0.0) 2 (100) Total 1776 (65.9) 918 (34.1) 2694 (100) Severity of injury No apparent injury 81 (64.8) 44 (35.2) 125 (100) 0.048 Minor 1102 (67.0) 543 (33.0) 1645 (100) Moderate 533 (65.6) 280 (34.4) 813 (100) Severe 60 (54.1) 51 (45.9) 111 (100) Total 1776 (65.9) 918 (34.1) 2694 (100) Abstract 432 Table 5Distribution of injuries by outcome and mechanism of injury among children attending emergency of hospitals in Makwanpur district, Nepal, April 2019 – March 2020Outcome of injuryDischargedAdmittedTransferredDiedLAMAUnknownTotalIntent & mechanismsn (%)n (%)n (%)n (%)n (%)n (%)n (%)Unintentional Fall 787 (86.5) 65 (7.1) 53 (5.8) 0 (0.0) 4 (0.4) 1 (0.1) 910 (100) Animal/insect bite/sting 704 (96.7) 3 (0.4) 19 (2.6) 0 (0.0) 1 (0.1) 1 (0.1) 728 (100) Road traffic injury 260 (73.0) 47 (13.2) 44 (12.4) 5 (1.4) 0 (0.0) 0 (0.0) 356 (100) Injured by a blunt force 190 (94.5) 4 (2.0) 6 (3.0) 0 (0.0) 1 (0.5) 0 (0.0) 201 (100) Stabbed, cut or pierced 165 (93.8) 8 (4.5) 3 (1.7) 0 (0.0) 0 (0.0) 0 (0.0) 176 (100) Fire, burn or scald 52 (80.0) 12 (18.5) 1 (1.5) 0 (0.0) 0 (0.0) 0 (0.0) 65 (100) Poisoning 30 (57.7) 4 (7.7) 16 (30.8) 1 (1.9) 1 (1.9) 0 (0.0) 52 (100) Suffocation/choking/asphyxia 24 (66.7) 4 (11.1) 6 (16.7) 1 (2.8) 1 (2.8) 0 (0.0) 36 (100) Electrocution 7 (58.3) 2 (16.7) 2 (16.7) 1 (8.3) 0 (0.0) 0 (0.0) 12 (100) Drowning and submersion 4 (57.1) 0 (0.0) 0 (0.0) 3 (42.9) 0 (0.0) 0 (0.0) 7 (100) Other 12 (92.3) 1 (7.7) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 13 (100) Unknown 2 (100) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 2 (100) Total 2237 (87.5) 150 (5.9) 150 (5.9) 11 (0.4) 8 (0.3) 2 (0.1) 2558 (100) Self-harm Poisoning 5 (13.2) 8 (21.1) 23 (60.5) 0 (0.0) 2 (5.3) 0 (0.0) 38 (100) Hanging 1 (8.3) 0 (0.0) 1 (8.3) 10 (83.3) 0 (0.0) 0 (0.0) 12 (100) Stabbed, cut or pierced 6 (100) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 6 (100) Injured by blunt object 4 (100) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 4 (100) Other 1 (100) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 1 (100) Total 17 (27.9) 8 (13.1) 24 (39.3) 10 (16.4) 2 (3.3) 0 (0.0) 61 (100) Assault Bodily force (physical violence) 34 (79.1) 5 (11.6) 3 (7.0) 0 (0.0) 1 (2.3) 0 (0.0) 43 (100) Injured by blunt object 18 (100) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 18 (100) Stabbed, cut or pierced 6 (75.0) 1 (12.5) 1 (12.5) 0 (0.0) 0 (0.0) 0 (0.0) 8 (100) Pushing from a high place 2 (100) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 2 (100) Poisoning 1 (50) 0 (0.0) 1 (50.0) 0 (0.0) 0 (0.0) 0 (0.0) 2 (100) Sexual assault 1 (100) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 1 (100) Other 1 (100) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 1 (100) Total 63 (84.0) 6 (8.0) 5 (6.7) 0 (0.0) 1 (1.3) 0 (0.0) 75 (100) Abstract 432 Figure 1Seasonal variation of injuries identified by the injury surveillance system over a year among children attending emergency of hospitals in Makwanpur district, Nepal, April 2019 – March 2020Results/ConclusionsThe total number of ED patients with injury in the study was 10,154.2,696 were patients aged <18 years. Most injuries in children were unintentional and over half of children presenting with injuries were <10 years of age. Falls, animal bites/stings and road traffic injuries accounted for nearly 75% of all injuries with some (drowning, poisonings and burns) under-represented. Over half of injuries were cuts, bites and open wounds. The next most common injury types were superficial injuries (14.2%); fractures (11.1%); sprains/dislocations (9.0%). Child mortality was 1%.This is the biggest prospective injury surveillance study in a low or middle country in recent years and supports the use of injury surveillance in Nepal for reducing child morbidity and mortality through improved data.CHILD PAPER: RESULTS SECTIONTotal number of ED patients: 33046Total number of ED patient with injury: 10154 (adult=7458 & children=2696)8.2% (n=2696) patients with injury were children aged <18 yearsHetauda hospital: 2274 (84.3%)Chure hill hospital: 422 (15.7%)

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BackgroundChest pain is a common cause for contacting the EMS, representing 10–15% of all EMS missions. Within this group only 15% suffer from a high-risk condition. It is an important, but challenging, task to identify these patients in need of prompt hospital care.ObjectiveTo identify prehospital predictors of high-risk conditions among EMS patients with chest pain.MethodsWe prospectively included 2917 consecutive EMS missions concerning patients with chest pain. Data regarding, medical history, symptoms, vital parameters and troponin were collected. All patients were classified as having high-risk condition or not. High-risk condition was defined as a time-sensitive diagnose with high mortality rates in need of immediate care (based on diagnose on hospital discharge).ResultsIn total 16% of included missions concerned a patient with a high-risk condition. In total 24 factors showed significantly increased odds of having a high-risk condition (table 1). Several factors also predicted lowered odds of high-risk condition.Abstract PP13 Table 1Factors predicting high-risk conditions, sorted by confidence interval (CI)Total with variable% (n)Patients with high-risk condition% (n)Patients without high-risk condition% (n)High-risk vs without high-risk, p-value*Odds RatioCI 95%All 100.0 (2917) 16.0 (467) 84.0 (2450) - - - ECG - ST-Elevation 6.1 (164) 22.9 (102) 2.8 (62) < 0.001 8.337 5.520–12.593 Prehospital Troponin T >50 ng/L 11.2 (168) 35.2 (90) 6.3 (78) < 0.001 6.382 4.469–9.115 ECG - ST-Depression 7.6 (204) 23.8 (106) 4.4 (98) < 0.001 4.629 3.225–6.646 Age ≥65 years 65.2 (1902) 76.7 (358) 63.0 (1544) < 0.001 3.866 2.608–5.740 NRS ≥9 5.1 (127) 10.0 (41) 4.1 (86) < 0.001 3.245 2.169–4.854 Pain in right arm 8.4 (145) 16.4 (48) 6.8 (97) < 0.001 2.886 1.967–4.235 Pale 16.4 (386) 29.1 (111) 14.0 (275) < 0.001 2.411 1.858–3.128 Age 51–64 years 18.5 (539) 17.1 (80) 18.7 (459) < 0.001 2.780 1.779–4.344 Male sex 50.2 (1465) 63.8 (298) 47.6 (1167) < 0.001 2.090 1.699–2.573 Debut during activity 22.1 (479) 32.8 (116) 20.0 (363) < 0.001 2.113 1.632–2.735 Pain between scapulars 2.2 (37) 4.1 (12) 1.8 (25) 0.003 2.980 1.449–6.132 Pain in left arm 24.0 (412) 33.6 (98) 22.0 (314) < 0.001 1.861 1.406–2.462 Central pain 53.4 (1215) 64.5 (240) 51.2 (975) < 0.001 1.746 1.381–2.207 NRS ≥6 32.1 (803) 38.9 (159) 30.8 (644) < 0.001 1.607 1.283–2.014 Constant pain 55.5 (1212) 61.8 (235) 49.9 (977) < 0.001 1.625 1.277–2.068 Clammy 8.7 (204) 14.4 (55) 7.6 (149) < 0.001 1.512 1.275–1.794 Pain in jaw 5.3 (92) 7.5 (22) 4.9 (70) 0.014 1.907 1.142–3.184 Breathing rate ≥25 breaths/min 10.2 (297) 14.7 (68) 9.4 (229) 0.007 1.505 1.118–2.026 Band-shaped pain 3.3 (58) 5.2 (15) 3.0 (43) 0.031 1.974 1.064–3.662 Quick debut, within minutes 35.2 (718) 42.7 (149) 33.6 (569) 0.004 1.194 1.059–1.346 ECG - Premature Atrial Contractions, PAC 3.5 (94) 6.1 (27) 3.0 (67) 0.034 1.799 1.046–3.095 Pain in right shoulder 4.2 (72) 6.2 (18) 3.8 (54) 0.035 1.830 1.042–3.213 Oxygen saturation ≤91% 3.8 (110) 6.4 (30) 3.3 (80) 0.046 1.571 1.007–2.452 ECG - T-wave Inversion 14.5 (388) 22.7 (101) 12.8 (287) 0.046 1.412 1.007–1.980 *Logistic regression, adjusted for age and sexConclusionsSeveral factors available in the prehospital setting seem to be suitable for risk assessment of patients with chest pain. Combing these factors in a scoring tool might be a feasible way to improve prehospital risk assessment.

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5059 Background: NGR-hTNF (asparagine-glycine-arginine human tumor necrosis factor) is able to promote antitumor immune responses and to improve the intratumoral doxorubicin (D) uptake by selectively damaging tumor vessels. Methods: OC patients (pts) with progressive disease (PD) after ≥ 1 platinum/taxane regimen and with a platinum free interval lower than 6 months (PFI <6) or ranging from 6 to 12 months (PFI 6-12) received NGR-hTNF (N) 0.8 µg/m2 and D 60 mg/m2 on day 1 every 3 weeks. Primary endpoint of this phase 2 trial was response rate by RECIST criteria with a target of ≥ 6/37 responding pts. Secondary aims were progression free survival (PFS) and overall survival (OS). Results: 37 pts (median age 57 years; PS 0/1 32/5; PFI < 6/6-12 25/12; prior regimens 1-5) were enrolled. Median baseline peripheral blood lymphocyte count (PBLC) was 1.6/mL (interquartile range 1.2-2.1). In all, 177 cycles were given, with 18 pts (49%) receiving ≥ 6 cycles and 12 pts (32%) 8 cycles. Neither grade 3/4 adverse events (AEs) related to N nor increase of D-related AEs were noted. Common grade 1/2 AEs included chills (65%). Eight pts (23%; 95% CI 12-39) had partial response (PR; 2 with PFI < 6 and 6 with PFI 6-12; median duration: 8.2 months). Fifteen pts had stable disease (SD, 43%; 10 with PFI < 6 and 5 with PFI 6-12; median duration: 4.9 months) for an overall disease control (DC, PR+SD) rate of 66%. Mean changes from baseline in target tumor size after 2, 4, 6, and 8 cycles were 2%, -54%, -69%, and -77%, respectively. Median PFS was 5.0 months (95% CI 3.1-6.9) and median OS was 17.0 months (10.4-23.6). In pts with PFI < 6 or 6-12, median PFS were 3.8 and 7.8 months (p=.03) and median OS were 14.3 and 20.1 months (p=.14), respectively. Pts with DC had longer median OS than those with early PD (24.0 and 4.9 months, respectively, p=.02). Longer PFI (p=.03) and higher PBLC (p=.01) were associated with better PFS, while OS correlated only with PBLC (p=.001). In the subset with PFI < 6, pts with PBLC ≥ or < 1.2/mL (1st quartile) had median PFS of 4.9 and 2.6 months (p=.02) and median OS of 15.8 and 4.3 months (p=.0001), respectivel Conclusions: A randomized phase II trial is currently testing D ± NGR-hTNF in pts with PFI < 6 (refractory/resistant). The role of PBLC as blood-based biomarker deserves further investigation.

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Abstract Objective: The aim of the study was to ascertain the feasibility of cord blood screening to determine the prevalence of haemoglobinopathies by a cost-effective method. Background: High rate of consanguinity and intercousin marraiges are prevalent in the Sultanate of Oman, leading to an increase in haemoglobinopathies, which is of growing importance as knowledge of a population structure can be a unique aid in planning genetic services. Methods: 1864 consecutive cord blood samples were screened by HPLC using Biorad Variant II program between April 2005 & March 2006. Complete blood counts [CBC] were also obtained on Cell Dyn 4000 automated blood cell counter. All samples were then processed to isolate and store mononuclear leukocytes for subsequent molecular diagnostics. Results: We observed a 46.83% incidence of α-thalassaemia, based on significant amounts of Hb Barts on HPLC and low mean cell volume [MCV] & mean cell haemoglobin [MCH] on the CBC. Table : Neonatal Cord Blood Screening - HPLC and CBC data with Red Cell Indices Normal ATT HbS HbD HbE HbC ?BTT Values in parenthesis represent SD Mean HbF % 77.4[7.3] 76.4[8.7] 89.4[9.4] 78.1[1.2] 81.1[4.9] 80.2[7.8] 92.1[2.0] Mean HbA % 22.5[7.3] 23.6[8.2] 14.1[6.0] 13.7[9.9] 12.7[3.1] 13.1[4.5] 8.1[2.1] Mean Haemoglobin g/dl 15.4[1.8] 14.4[1.4] 14.7[1.6] 14.9[0.7] 15.6[1.1] 15.2[0.8] 13.9[2.5] Mean RBC Count × 1012/L 4.5[0.6] 5.0[0.6] 4.9[0.6] 4.5[0.4] 4.8[0.4] 4.6[0.2] 4.0[0.6] Mean MCV fl 105.2[5.4] 89.9[4.1] 95.1[9.1] 100.8[7.0] 98.1[4.7] 99.1[5.6] 104.4[9.5] Mean MCH pg 34.4[2.1] 28.5[1.8] 30.7[3.4] 33.3[2.7] 32.6[3.3] 32.9[1.2] 34.8[1.0] Mean MCHC g/dL 32.7[1.1] 31.7[1.3] 32.2[1.0] 33.1[0.9] 33.6[2.1] 33.2[1.5] 33.3[1.0] Mean RDW % 16.1[1.1] 17.4[2.1] 17.1[2.4] 16.1[1.5] 17.7[2.4] 16.5[1.9] 16.1[2.5] Furthermore, the overall incidence of other haemoglobinopathies was 9.39%, with 6.01% incidence of sickle haemoglobin. On HPLC, D-window, E-window and C-window were present in 1.02%, 0.32% and 0.11% of the samples respectively. Figure: Distribution of abnormal Haemoglobins in Newborns Figure:. Distribution of abnormal Haemoglobins in Newborns Since HPLC cannot diagnose β-thalassemia major at birth, in samples with HbA below 10%, the beta globin gene was directly sequenced including the promoter, all exons and introns in the abnormal samples. [n=36] Additionally, direct sequencing of abnormal samples with HbS,[n=112] HbD,[n=19], HbE[n=6] and HbC[n=2] were also performed to validate the HPLC results. Conclusions: It is emphasized that neonatal cord blood screening is an important the first step in the national strategy towards total management of haemoglobinopathies including early diagnosis, comprehensive clinical care and counseling of the affected families. Between group differences were significant for RBC count, MCV, MCH, MCHC and the red cell distribution width (RDW), which along with Hb Barts, and HPLC results can successfully predict the correct underlying diagnosis.

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INTRODUCTION. A number of studies demonstrate the advantage of bilateral mediastinal lymphadenectomy in surgery of non-small cell lung cancer (nSCLC). For surgical approach to the opposite mediastinum for many years there were proposed sternotomy, video-thoracoscopy, and transcervical video-assisted interventions. In our practice, we use videoassisted mediastinal lymphadenectomy (VAMLA).The OBJECTIVE was to learn the efficiency and safety of VAMLA in surgery of NSCLC.METHODS AND MATERIALS. The study included the materials of examination and treatment of 102 patients with NSCLC. 102 patients were divided into 2 groups. In the 1st group (54 patients), VAMLA and lung resection were performed. In the 2nd group (48 patients): anatomical lung resection and systematic ipsilateral lymphadenectomy (SLD) were performed.RESULTS. The average number of remote lymph node stations in group 1 was (7.8±1.7); in group 2 – (4.5±1.2) (p<0.05). The average number of lymph nodes was 26±8.6 compared to (14.3±6) in both groups, respectively (p<0.05). «Occult» pN2-N3 metastasis was detected in 20 % (7/34) of patients of the group 1 and 6.5 % (2/31) of patients of the group 2 (p<0.05). The level of postoperative complications in both groups was 33.4 vs. 29.2 %, respectively (p>0.05). The duration of the postoperative day ((12.7±4.9) vs. (13.7±6.5)) and the duration of pleural drainage ((5.5±4.2) vs. (5.8±4.4)) did not differ in both groups (p>0.05).CONCLUSION. VAMLA is an effective and safe method for evaluating the pN stage of NSCLC. Performing VAMLA in left-sided NSCLC allows removing significantly more lymph nodes and stations in comparison with SLD available in VATS and thoracotomy, which increases the accuracy of postoperative N-staging. The use of the VAMLA in minimally invasive surgery of right-sided NSCLC may be promising in cases of high risk of «occult» pN3 lesion, but requires further study of the role of contralateral lymphatic dissection.

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Background and purposeFlow diverters are increasingly used for the treatment of intracranial aneurysms. Evaluation of the first devices available for clinical use showed high efficacy of this treatment although safety results were worse compared with coiling or balloon-assisted coiling. The Safety and Efficacy Analysis of FRED Embolic Device in Aneurysm Treatment (SAFE) trial is a single-arm, multicenter, prospective study conducted to precisely analyze the safety and efficacy of the FRED and FRED Jr devices.MethodsUnruptured and recanalized aneurysms located in the anterior circulation treated with FRED and FRED Jr were prospectively included. Adverse events were independently evaluated by a Clinical Event Committee with a vascular neurosurgeon and an interventional neuroradiologist. Primary safety outcome measures were morbidity and mortality rates at 6 months after treatment.ResultsA total of 103 patients/aneurysms were included in 13 interventional neuroradiology (INR) centers. Aneurysm locations were supraclinoid internal carotid artery (ICA) in 71 (68.9%), cavernous ICA in 15 (14.6%), anterior cerebral artery or anterior communicating artery in nine (8.7%), and middle cerebral artery in eight (7.8%). Aneurysms were small (<10 mm) in 71 patients (68.9%). Treatment was successfully performed in 98/103 patients (95.1%). Thromboembolic (TE) complications occurred in 5/103 patients (4.9%), intraoperative rupture in 2/103 patients (1.9%), delayed aneurysm rupture in 1/103 patient (1.0%), and delayed hematoma occurred in 1/103 patient (1.0%). Six-months' mortality and morbidity rates were 1/102 (1.0%) and 2/102 (2.0%), respectively.ConclusionsAneurysm treatment with the FRED device is safe with low mortality (1.0%) and morbidity (2.0%).Clinical trial registrationNCT02921698.

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Aims/Objectives/BackgroundPaediatric presentations to the emergency department (ED) reduced significantly during the COVID-19 lockdown. Concerns were raised that children were coming to harm as a result of delayed presentations to ED and rapid guidance was produced for parents to highlight red and amber symptoms which should prompt ED review. NHS 111 responses were also adapted for children to facilitate rapid recognition of the sick child.The aim of this rapid surveillance project was to objectively describe the proportion of children who had a delayed presentation to ED during the COVID-19 lockdown and their need for admission.Methods/DesignProspective anonymous data collection on children presenting to ED during periods between 20th April and 8th July 2020 in 7 trusts in England and Northern Ireland. Clinicians (doctors and advance care practitioners) were asked to feedback at the time of patient dispostion about whetherthe parents had reported a delay in presenting to hospitalthe parents had experienced a delay secondary to another service provider (primary care/111)there was no delay in presentationthey were uncertain as to whether there was a delay.Data was a collected via an approved website with appropriate data goverance.Abstract 382 Table 1Patient characteristics and outcomesAgeNRed SxAmber Sx111/GP inputParental delayGP/111 delayAdmission to PICU if delayedAdmission to ward if delayed0–6 weeks 67 7 (10.4%) 19 (28.4%) 23 (34.3%) 3 (4.5%) 0 (0.0%) 1 (33.3%) 1 (33.3%) 7 weeks - 3 months 51 4 (7.8%) 17 (33.3%) 50 (98.0%) 0 (0.0%) 1 (2.0%) 0 (0.0%) 0 (0.0%) 4–6 months 47 7 (14.9%) 11 (23.4%) 22 (46.8%) 4 (8.5%) 4 (8.5%) 0 (0.0%) 0 (0.0%) 7–11 months 116 10 (8.6%)22 (19.0%) 50 (43.1%) 2 (1.7%) 0 (0.0%) 0 (0.0%) 0 (0.0%) 1 year 198 15 (7.6%) 43 (21.7%) 58 (29.3%) 4 (2.0%) 3 (1.5%) 0 (0.0%) 1 (14.3%) 2–5 years 471 14 (3.0%) 98 (20.8%) 107 (22.7%) 11 (2.3%) 1 (0.2%) 1 (8.3%) 1 (8.3%) 6–10 years 388 22 (5.7%) 112 (28.9%) 105 (27.1%) 17 (4.4%) 4 (1.0%) 0 (0.0%) 3 (14.3%) 11–15 years 299 22 (7.4%) 64 (21.4%) 64 (21.4%) 12 (4.0%) 2 (0.7%) 0 (0.0%) 3 (21.4%) Total 1637 101 (6.2%) 386 (23.6%) 449 (27.4%) 53 (3.2%) 15 (0.9%) 2 (2.9%) 9 (13.2%) Sx: Signs (as per RCPCH guidance)PICU: Paediatric Intensive Care UnitResults/Conclusions1637 patients patient entries were recorded, the majority in May 2020 (86%). Patient characteristics and outcomes are shown in table 1.Diagnosis of 11 patients with delayed presentation requiring admission: sepsis, abdominal pain of unclear cause, abscess, bronchiolitis, headache, GORD, DKA, testicular torsion and viral induced wheeze.1 in 24 children were reported to have delayed presentation during lockdown and a small number of these children required PICU admission.Overall the data are reassuring that the majority of children are brought to ED appropriately. Ongoing messaging for parents regarding red and amber symptoms continues to be important, particularly in the event of any further lockdowns.

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In anesthetized paralyzed term newborn rabbits at various postgestational ages (from birth up to 16 days), we measured by micropuncture technique the hydraulic pressure of the pulmonary interstitium (Pip), the extrapleural parietal interstitium, and the pleural liquid. Birth data refer to cesarian-delivered nonbreathing rabbits. Pip increased from 0.5 +/- 2 to 6 +/- 0.7 cmH2O from birth up to 2 h and then decreased, becoming subatmospheric at 5 h and attaining -6 +/- 1.6 cmH2O at 16 days. Over the same period of time, pressure in the extrapleural parietal interstitium and the pleural liquid remained fairly constant at an average value of approximately -1.5 and -2 cmH2O, respectively. The wet-to-dry weight ratio of the lungs decreased from 7.8 +/- 0.4 to 4.9 +/- 0.1 at 16 days. Plasma protein concentration was 4.2 +/- 0.4 g/dl at birth, decreased to 3.2 +/- 0.5 g/dl at 1 h from delivery, and increased back to 4 +/- 0.6 g/dl at 16 days. Pleural liquid protein concentration was 3 +/- 0.1 g/dl at birth and decreased to 1.2 +/- 0.2 g/dl at 16 days. In the first hours of postnatal life, the marked increase in Pip appears to be a key factor in favoring fluid clearance from pulmonary interstitium into the pulmonary capillaries and the pleural space. This factor vanishes after approximately 6 h because of the marked decrease in Pip.

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The diversity of free-living aquatic nematodes is largely unknown for the Gulf of Mexico and Caribbean Sea. The Cuban Archipelago is an important part of this because of its large area and diversity of habitats. We analyzed the free-living nematodes from 83 sites from seven aquatic habitats around Cuba, to produce a checklist for many habitats, including seagrass meadows, coral degradation zones, algal turf, bare sands, unvegetated muds, freshwater and anchihaline caves, and deep-sea sediments. The checklist contains 469 species, 229 genera, 50 families, and 9 orders. Chromadorida, Enoplida, and Monhysterida were the best represented orders with 112, 100, and 83 species respectively. The most abundant species were Euchromadora vulgaris, Terschellingia longicaudata, Desmodora pontica, Sabatieria pulchra , and Epsilonema sp. Most of the listed species were new records for the region. There were differences in the number of species recorded in each habitat type, with seagrass meadows having 280 species, coral degradation zones having 139 species, deep waters having 116 species, algal turf having 114 species, bare sands having 100 species, unvegetated muds having 78 species, freshwater caves having 19 species, anchihaline caves having 16 species, and freshwater streams having 6 species. The checklist is the most comprehensive recent report of the diversity of free-living nematodes in the regions of Gulf of Mexico and Caribbean Sea. The reported diversity is higher than many other regional checklists likely reflecting the intense sampling effort and the variety of microhabitats in Cuban Archipelago.

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Abstract Background ABS is one of the most common infections in childhood leading to antibiotic prescriptions, but remains a clinical diagnosis. Laboratory testing does not aid diagnosis and there are no predictors to identify those who will respond to therapy or develop complications. Thus, the tools to diagnose and manage ABS remain limited. Initial viral infection predisposes to development of ABS. However, there is poor understanding of the contribution of viral infection to pathogenesis, rate of complications, or the immune response to ABS. The objective of this study was to define bacterial upper airway colonization, viral co-infection and cytokine response in the upper airway during ABS. Methods In the context of an ongoing larger prospective clinical study, children were enrolled who were diagnosed with ABS using standardized clinical criteria. Nasopharyngeal (NP) samples were processed for bacterial culture for S. pneumoniae, H. influenzae, S. pyogenes and M. catarrhalis; real-time PCR viral testing and cytokine measurement by qPCR. We correlated these findings with clinical symptoms at the time of presentation. Results Of 184 enrolled children (median age 4.9 years), 134 (72.8%) had a positive bacterial culture for potentially pathogenic bacteria and 50 (27.2%) had growth of normal flora. A total of 129 (70.4%) subjects tested positive for a virus. The most common virus detected was rhinovirus (n = 86) followed by influenza virus (n = 23) and adenovirus (n = 21). A total of 102 patients (70.4%) had both a positive pathogenic bacterial culture and viral detection. Patients who had a bacterial pathogen plus a viral detection had a significantly higher expression of IL-6, IL-8 and IL-25 (P &lt; 0.001). Univariable analysis found no correlation between clinical presentation with viral and/or cytokine expressions. Conclusion Children meeting clinical criteria for ABS and a NP swab with a pathogenic bacteria plus viral detection demonstrated higher expression of inflammatory cytokines compared with subjects whose culture had normal respiratory flora. Disclosures J. V. Williams, Quidel: Board Member, Consulting fee. GlaxoSmithKline: Consultant, Consulting fee.

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AbstractThe occurrence of LDE-type flares in the last three cycles has been investigated. The Fourier analysis spectrum was calculated for the time series of the LDE-type flare occurrence during the 20-th, the 21-st and the rising part of the 22-nd cycle. LDE-type flares (Long Duration Events in SXR) are associated with the interplanetary protons (SEP and STIP as well), energized coronal archs and radio type IV emission. Generally, in all the cycles considered, LDE-type flares mainly originated during a 6-year interval of the respective cycle (2 years before and 4 years after the sunspot cycle maximum). The following significant periodicities were found:• in the 20-th cycle: 1.4, 2.1, 2.9, 4.0, 10.7 and 54.2 of month,• in the 21-st cycle: 1.2, 1.6, 2.8, 4.9, 7.8 and 44.5 of month,• in the 22-nd cycle, till March 1992: 1.4, 1.8, 2.4, 7.2, 8.7, 11.8 and 29.1 of month,• in all interval (1969-1992):a)the longer periodicities: 232.1, 121.1 (the dominant at 10.1 of year), 80.7, 61.9 and 25.6 of month,b)the shorter periodicities: 4.7, 5.0, 6.8, 7.9, 9.1, 15.8 and 20.4 of month.Fourier analysis of the LDE-type flare index (FI) yields significant peaks at 2.3 - 2.9 months and 4.2 - 4.9 months. These short periodicities correspond remarkably in the all three last solar cycles. The larger periodicities are different in respective cycles.

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Abstract Background: Unraveling the cytogenetic background helped to decipher the molecular basis of many hematologic cancers and to develop specific therapies. Recently, using chromosome banding analysis (CBA), jumping translocations were identified as a cause of 17p loss in multiple myeloma, providing new insights into the origin of clonal evolution and copy number alterations (CNA) (Sawyer et al, Blood 2014). In chronic lymphocytic leukemia (CLL) the genomic mechanisms leading to 17p loss are not fully understood. Aims: Characterization of underlying mechanisms of 17p loss using CBA and correlation with other clinicobiological features in “ultra high-risk” CLL. Methods: Samples from 112 patients (pts.) with refractory and/or 17p- CLL enrolled in the multicenter CLL2O trial were screened for CNAs by Affymetrix 6.0 SNP array analysis of CD19 sorted CLL cells and for chromosomal abnormalities by CBA using CpG oligonucleotide and interleukin-2 stimulation. Results: Considering both CBA and SNP data, 728 aberrations resulted in a mean of 6.5/case. 89 (79%) pts. had 17p deletion and 83 (74%) TP53 mutation. Regarding the origin of 17p/TP53 loss, 6 distinct types of rearrangements could be delineated: 1) whole arm translocations (WAT) 2) jumping translocations (JT) 3) dicentric chromosomes (DC) 4) cytogenetically balanced translocations (CBT) 5) other unbalanced translocations and 6) interstitial 17p deletions. WAT were identified in 33/112 (30%) cases and 30/33 (91%) involved chromosome 17 leading to 17p loss. Chromosomes involved ≥ 2 times in an unbalanced WAT were der(17;18)(q10;q10) (8, 24%), der(8;17)(q10;q10) (5, 15%), der(15;17)(q10;q10) (4, 12%), i(17)(q10) (4, 12 %), der(17;22)(q10;q10) (2, 6%). JT were identified in 11 (10 %) cases, 6 showing jumping WAT with 17q as donor chromosome, 1 case with breakpoints located in the pericentromeric regions of chromosome 17p11 (donor chromosome) and the receptor chromosomes 4p14 and 16p11. In 4 cases, initially a WAT involving 17q occurred and subsequently the partner chromosome “jumped off” leaving a 17p deletion behind. DC were detected in 19 pts., 8 with breakpoint in 17p11, 7/8 with TP53 mutation. Of note, all cases had the breakpoint on chromosome 17 in 17p11 indicating a fragile site affecting the pericentromeric region. Interestingly, of a total of 382 translocations observed by CBA, only 32 were CBT and except for those involving the IGH and IGK/L loci (n=6) all were random. 17p involvement in CBT was detected in 4 cases, 3 had TP53 deletion and all were TP53 mutated. Of the unbalanced translocations, der(17)t(8;17) was identified in 5 pts. simultaneously generating 8q gain. Nevertheless, breakpoints on chromosome 17p covered cytobands 17p11-13 and on chromosome 8, 8q11-22, one case having the breakpoint telomeric to the TP53 locus and no TP53 mutation, pointing to other putative candidate genes on 17p. In 36/112 (32%) cases, 17p deletion was induced by random rearrangements. Interstitial 17p deletions were identified in only 9/112 (8 %) cases. According to the inclusion criteria of the trial, 36/112 (32%) pts. had 17p deletion and were treatment-naïve while 76/112 (68%) were relapsed or refractory to fludarabine or bendamustine based therapy, 53/76 (70%) having a 17p deletion. Treatment naïve pts. had a mean of 7.36 aberrations/case and pretreated pts. 6.09/case. Focusing on WAT and JT, 18/33 (54%) pts. with WAT and 7/11 (63%) pts. with JT were pretreated whereas 57/78 (73%) pts. in the other cytogenetic subgroups had prior therapy exposure. Considering other genomic features, WAT and JT occurred almost exclusively within complex karyotypes (≥3 chromosomal aberrations), 31/33 WAT and 10/11 JT, were IGHV unmutated, 30/33 WAT and 11/11 JT and harbored TP53mutations, 29/33 WAT and 10/11 JT. Conclusions: “Ultra high-risk” CLL pts. are characterized by a high genomic complexity as compared to standard risk treatment-naïve CLL pts. (CLL8 trial with 1.8 CNAs/case). Previous genotoxic therapy had no influence on the total number of aberrations or the underlying mechanism, suggesting an intrinsic genomic instability of the tumor cells with TP53 alterations. WAT and JT emerged as nonrandom aberrations involved in 17p loss. Given the strong association of TP53 deletion with TP53 mutations of the remaining allele, one may speculate that TP53 mutations precedes TP53 deletion by disrupting the normal DNA repair mechanisms permitting incorrect recombinations. Disclosures Stilgenbauer: Amgen: Honoraria, Research Funding; Genzyme: Honoraria, Research Funding.

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Estudamos cirurgias colorretais do SC-HU/UFS (Serviço de Coloproctologia do Hospital Universitário da Universidade Federal de Sergipe) realizadas de janeiro de 2004 a julho de 2006, série histórica da criação da residência médica em coloproctologia. De setenta pacientes, 53(75,7%) eram do gênero masculino, 17(24,3%) feminino; idade variou de 19 a 85 anos com média de 52 anos. Os setenta pacientes foram submetidos a 102 procedimentos, com média de 1,4 cirurgias/paciente, 29(28,4%) reoperações. Dezenove(18,6%) foram reconstituições de trânsito intestinal, 15(14,8%) retossigmoidectomias, 11(10,8%) colectomias totais, 9(8,8%) colectomias direitas, 6(5,8%) amputações abdomino-perineais, 3(2,9%) proctocolectomias, 2(1,9%) colectomias esquerdas. Dezoito(17,6%) cirurgias indicadas por neoplasias de cólon, 8(7,8%) do reto e 1(0,9%) do canal anal; 10(9,9%) foram megacólon; 10(9,9%) colostomias prévias, 5(5,9%) Doença de Crohn, 5(4,9%) DDC, 3(2,9%) RCUI. Quarenta e oito(47,1%) cirurgias tiveram complicações cirúrgica: 32(31,4%) complicações da ferida operatória, 13(12,7%) abscessos abdominais, 11(10,8%) fístulas, 7(6,9%) deiscências, etc. Índice de infecção de ferida foi 26,5%. Cinqüenta e cinco pacientes(53,9%) foram submetidos à anastomose, 32(58,2%) manuais e 23(41,8%) mecânicas. Deiscência de anastomose em 7(12,7%) cirurgias: 1(3,1%) deiscência em anastomose manual e 6(26,1%), em mecânica. Óbito em 11(15,7%) pacientes. Avaliamos principais dados do trabalho objetivando definir metas, elaborar e melhorar protocolos vigentes objetivando otimizar o programa de residência médica.

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4022 Background: Sonic Hh (SHh), the ligand for the Hh pathway, is over-expressed in >80% of PC. V, a small molecule antagonist of the Hh signaling pathway, has activity in preclinical PC models. Methods: We conducted a multi-center, placebo-controlled, phase IB/randomized phase II trial of GV or GP. Eligible pts, KPS 80-100, had previously untreated metastatic PC, or had completed adjuvant therapy > 6 months (mo) prior. Primary endpoint: progression-free survival (PFS). Correlatives: serial SHh serum levels; serial contrast perfusion CT imaging. To allow for early stopping due to lack of efficacy, a planned interim analysis was performed after approximately 50% of the expected number of PFS events occurred. The protocol stipulated that the trial would be terminated if the probability of rejecting the null hypothesis were the trial to continue (conditional power) was <10%. All pts received G 1000mg/m2 over 30 minutes, days (D) 1, 8, 15, Q28D. Pts, stratified by KPS (80 v 90/100), and disease status (newly-diagnosed/recurrent), were randomized to V (150 mg PO daily) or P. For pts on P, cross-over was allowed at progression. Results: 70 evaluable pts (V/P 35/35) enrolled at 12 sites 2/10-6/11. Pt characteristics: median age 63/63 (range 49-79/48-82); KPS 80: 8/8; 90: 12/14; 100: 15/13. Grade 3/4 toxicity (%pts): neutropenia 20/26; hyponatremia 3/11; fatigue 9/6; hyperglycemia 14/6; elevated alkaline phosphatase 9/11. Response (%): complete 0/3, partial 0/11, stable disease 49/31. Median PFS: 3.7/2.4 mo (95% CI: 2.4-4.6/1.9-3.7; adjusted HR 0.92 [0.52-1.64]). Upon progression/unblinding, 23 GP pts crossed over to GV. Median overall survival (OS): 6.3/5.4 mo (95% CI:4.9-7.8/4.2-8.0, adjusted HR 0.97, [0.47-2.01]). 1-year survival (%): 24/24. Laboratory and radiological correlatives will be presented. Conclusions: GV has an acceptable toxicity profile. This trial did not meet criteria for futility at this interim analysis. The study is expected to complete accrual of 112 pts in February 2012. The final analysis will be reported after 90 events. Funded by NCI N01-CM-62201.

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Background:Current guidelines for the treatment of rheumatoid arthritis (RA) recommend early administration of methotrexate (MTX) and addition of a biologic if MTX monotherapy does not provide remission or low activity of the disease. Efficacy of this strategy in real clinical practice was assessed using data from the Russian RA registry OREL.Objectives:To analyze long-term results of intensive treatment initiated at RA onset in real clinical practice.Methods:141 RA patients with disease duration less than 3 years (29 men, 112 women) were included. 112 were positive for rheumatoid factor and 119 – for anti-cyclic citrullinated peptide antibody. Subcutaneous MTX was initiated at 10-15 mg per week with further dose escalation up to 20-30 mg per week. Therapy was adjusted every 3 months. If MTX monotherapy did not allow to achieve treatment target of remission or low disease activity, biologics were added.Results:Median DAS 28 at baseline was 5,31 [4,79; 6,14]. Initiation of treatment resulted in steady decrease of disease activity (p<0.05, table1). After 1 year of follow-up 33.8% of patients received MTX monotherapy, 33.8% – MTX in combination with tumor necrosis factor alpha inhibitors, 22.0% – MTX +abatacept, 0.55% – MTX+ tocilizumab, 0.47% – MTX + rituximab. Low disease activity was achieved in 16.3% patients, and remission - in 45.8%. After 6 years median age of patients was 58 [49; 66] years, disease duration – 84 [79; 89] months, low disease activity was documented in 21.3%, and remission – in 7.8% of cases (fig. 1). 7% of patients were able to maintain remission without any treatment. Biologics were discontinued in 15 patients after achieving remission or low disease activity, and synthetic DMARDs – in 5 patients having remission.Conclusion:Intensive therapy initiated at RA onset demonstrates high effectiveness, allowing 61.5% of patients to achieve low disease activity or remission within 12 months, and to maintain these results after 6 years of treatment in 29.2%. Adherence to this strategy allowed to discontinue biologics in 15 patients and synthetic DMARDs in 5 patients after achieving treatment target.Figure 1.Changes of the disease activity during follow-upTable 1.Changes of the main inflammatory activity measures, Me [25th; 75th percentile]Parametres012 months6 yearsDAS285,31 [4,79; 6,14]2,85 [2; 3,90] *4,008 [3,4; 4,59] *SDAI28,27 [18,79; 40,73]5,67 [2; 11,98] *15,06 [9,32; 21] *CDAI25 [17; 36]5 [1,7; 11] *15 [9; 21] *ESR (mm/hr)32 [19; 50]16 [8; 30] *16 [10; 25] *CRP (mg/l)26,55 [6,4; 45,30]3,85 [1,5; 11,3]*2,2 [0,9; 4,9] ** p<0.05 in all cases.Disclosure of Interests:None declared

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Abstract Mantle cell lymphoma (MCL) is an aggressive and incurable B-cell NHL characterized by a high relapse rate. Novel treatments capable of providing and/or sustaining more durable responses in MCL patients are clearly needed. Manipulation of the immune system to unleash its protective effect might induce durable responses in MCL. To effectively harness the immune system against MCL, it is important to understand how T-cells interact with malignant B-cells that reside where immune responses are normally initiated. In the present study, we evaluated the number and phenotype of T-cells present in the lymph nodes of 14 patients with MCL. Given the increasingly important role of T regulatory cells (Tregs) and the paucity of information regarding their role in MCL, we also evaluated if T-cells infiltrating the lymph node of MCL patients co-express CD4 and FoxP3. Our patients consisted of 1 woman and 13 men, age range from 49–78 (mean age 65), 6 previously treated with chemotherapy, and 8 de novo. There was heterogeneity in the CD3+ T cell populations in our patients (range 2.7–55% [mean 15.8%]). Double staining with CD4/FoxP3 (range 0.2–3.4% [mean 1.7%]) and CD8/FoxP3 (range 0–3.2% [mean 1.4%]) showed significant heterogeneity in both populations (Table 1). A significant portion of FoxP3 positive, CD4/CD8 negative cells were seen in several cases (range 0–16% [mean 4.9%]). Flow cytometry was run on all 14 cases to evaluate the T cell populations. Spearman non-Gaussian regression analysis (using GraphPad™ software) comparing the CD4/FoxP3+ and CD8/FoxP3+ cells to the total CD8 cells showed a negative correlation by both immunohistochemical and flow, confirming that as the Treg population increases the CD8 population decreases (Table 2). Correlating CD4 Treg with CD8 by flow cytometry and IHC indicated an inverse correlation in 7 of 14 cases. Only 1 case had a positive correlation. The remaining cases had no correlation. These findings suggest increasing FoxP3 populations in MCL could result in a decrease in CD8+ T cell immune response against the malignant cells. Future studies including the characterization of the non-CD4/CD8 FoxP3+ cells may help clarify the role of Tregs in MCL. Table 1: MCL T cell Populations CD3+ FLOW (%) Total FoxP3 IHC (%) CD4/FoxP3+ IHC (%) CD8/FoxP3+ IHC (%) CD4+ IHC (%) CD8+ IHC (%) CD4+ FLOW (%) CD8+ FLOW (%) 6.5 3.2 1.8 0.4 6.4 7.8 2 4 43 12.8 0.6 1 10.6 19.2 16 27 16 4.4 0.2 0.8 8.8 15.4 5 11 11 3.6 1.4 0 6.2 1.8 8 3 8.4 3.4 0.8 1.4 17.6 11.2 1.6 3.9 10 7.8 1.8 0.6 13.6 9.2 7.5 2.5 26 12.4 3.4 2.4 15.8 16.8 20 0.1 6.3 8.2 2.2 3.2 11.6 11 1.7 3.7 55 8.6 3.4 1 21 21.6 30 25 12 10.8 2.4 2 16.8 17 5.1 6 8.4 4.6 1.6 1.2 17.6 18 5.1 3.2 5.4 9.6 1.8 1.8 13.6 16 3.6 0.3 2.7 2.2 0.8 1.4 3.8 3.4 0.8 1.9 11 19 1.2 1.8 22 8.6 7.6 3.6 Table 2: Spearman Rank Correlation Group Spearman Rank Correlation 95% Confidence Interval CD4/FoxP3+ vs. CD8 (IHC) 0.2788 −0.3115 to 0.7138 CD4/FoxP3+ vs. CD8 (FLOW) −0.2614 −0.7045 to 0.3284 CD8/FoxP3+ vs. CD8 (IHC) 0.2558 −0.3337 to 0.7105 CD8/FoxP3+ vs. CD8 (FLOW) −0.2196 −0.6815 to 0.3673 CD4/FoxP3+ vs. CD4 (IHC) 0.3448 −0.2440 to 0.7479 CD4/FoxP3+ vs. CD4 (FLOW) 0.3636 −0.2237 to 0.7572 CD8/FoxP3+ vs. CD4 (IHC) 0.4044 −0.1777 to 0.7769 CD8/FoxP3+ vs. CD4 (FLOW) −0.2243 −0.6841 to 0.3630

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Abstract Abstract 2069 Introduction: Mechanisms leading to pulmonary hypertension (PHT) in patients with thalassemia intermedia (TI) are still controversial. Moreover, clinical and laboratory characteristics of patients who eventually develop PHT have not been identified. Our aim was to identify factors that characterize TI patients who develop PHT. Methods: Data was retrospectively retrieved from the Thalassemia Intermedia Registry, a database of 584 TI patients currently registered at six comprehensive care centers in Lebanon, Italy, Iran, Egypt, United Arab Emirates, and Oman. Institutional review boards at each center approved the study protocol. Two Groups of patients were identified: Group I, TI patients with documented PHT (n=64; mean age 37.3 ± 10.6; 44% males); and Group II, age- and sex-matched TI patients without PHT (n=64; mean age 37.9 ± 11.4; 44% males). Collected data included demographics, laboratory parameters, disease-complications, and received treatments that may influence PHT development and reflected the period prior to PHT occurrence. Results: There were no statistically significant differences in mean platelet counts, total or fetal hemoglobin levels between the two Groups. However, mean serum ferritin level was higher in Group I compared to Group II (1233.2 ± 499.2 vs. 654.7 ± 234.5 ng/ml; P=0.01). Moreover, mean nucleated red blood cell (NRBC) count was higher in Group I compared to Group II (354.2 ± 199.2 vs. 214.7 ± 94.5 ×10⋀6/l; P=0.03). A higher proportion of patients were splenectomized (84.4% vs. 46.9%; P<0.001) or had a previous history of thromboembolic events (40.6% vs. 7.8%; P<0.001) in Group I compared to Group II. Conversely, a higher proportion of patients received transfusion (78.1% vs. 56.2%; P<0.001), iron chelation (62.5% vs. 37.5%; P<0.001), or hydroxycarbamide (34.4% vs. 17.2%; P<0.001) therapy in Group II compared to Group I. There were no statistically significant differences in the proportion of patients with heart failure, prothrombotic mutations, or receiving antiplatelet or anticoagulant therapy between the two Groups. Multivariate logistic regression analysis revealed that patients in Group I are more likely to be splenectomized (OR:4.9, 95%CI:1.9-8.5); transfusion-naive (OR:3.5, 95%CI:2.1-6.25); on no hydroxycarbamide (OR:2.6, 95%CI:1.1-5.25) or iron chelation therapy (OR:2.3, 95%CI:1.2-4.25); and have NRBC count >300 ×10⋀6/l (OR:2.59, 95%CI:1.69-6.05) or a previous history of thromboembolism (OR:3.69, 95%CI:2.38-7.05). Conclusion: Splenectomy, previous history of thromboembolism, and a high NRBC count characterize TI patients who develop PHT. Transfusion, iron chelation, and hydroxycarbamide therapy deserve evaluation for a protective role against PHT in TI. Disclosures: No relevant conflicts of interest to declare.

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Background:Psoriatic arthritis (PsA) is a chronic inflammatory disease affecting the musculoskeletal system as well as skin and nails. The prevalence of depression in psoriasis and PsA is high and ranges from 7-40% [1]. Persistent depressive mood may influence disease activity outcome in PsA, especially patient-reported outcomes.Objectives:To assess the correlation of depressive symptoms with PsA-specific outcome parameters.Methods:RABBIT-SpA is a prospective longitudinal cohort study including PsA patients enrolled at start of a new conventional treatment or b/tsDMARD treatment. In regularly provided follow-up questionnaires, physician- and patient-reported information on the disease course including the depression screening tool WHO-5 to assess mental health is collected. For the current analysis, the WHO-5 score was categorised into 4 groups using validated cut-offs: severe depressive symptoms <13, moderate depressive symptoms 13-28, mild depressive symptoms 29-50, well-being >50. Spearman correlation coefficient was calculated to analyse the relationship between the WHO-5 score and various PsA related outcome parameters.Results:936 PsA patients were included. Baseline characteristics are shown in Table 1. In 411 patients (43.9%) the WHO-5 score indicated well-being, 249 (26.6%) had mild depressive, 203 (21.7%) moderate depressive and 73 patients (7.8%) severe depressive symptoms. WHO-5 results correlated with patient reported skin involvement (DLQI: -0.25, patient assessment skin: -0.17), and the composite scores DAPSA (-0.33) and DAS28 (-0.28) as well as with patient reported pain (-0.43) and patient global disease assessment (-0.42). The highest correlation was found for physician assessed global health status (-0.51) and PSAID (-0.62). No significant correlation was found with CRP, swollen joint count and physician assessed skin involvement including body surface area (BSA).Table 1.Baseline characteristics of patients included in the analysis stratified by WHO-5 categories.ParameterWHO-5 (<13) severeN=73WHO-5 (13-28) moderateN=203WHO-5 (29-50) mildN=249WHO-5 (>50) well-beingN=411TotalN=936Age, mean (SD)52.6 (11.4)51 (11.3)51.4 (12.5)52.8 (12.7)52 (12.2)Female, n (%)52 (71.2)127 (62.6)157 (63.1)227 (55.2)563 (60.1)Disease duration, years, mean (SD)8.3 (8.7)6 (7.9)6.2 (6.7)6.4 (7.5)6.4 (7.5)Dactylitis, n (%)14 (19.7)31 (15.5)46 (18.5)77 (18.8)168 (18.1)Axial involvement, n (%)14 (19.7)54 (26.9)49 (19.7)71 (17.3)188 (20.2)Nail involvement, n (%)34 (47.2)85 (42.3)106 (42.6)158 (38.6)383 (41.1)BMI>=30, n (%)37 (51.4)75 (37.1)98 (39.5)125 (30.9)335 (36.2)CRP of >=5 mg/L, n (%)33 (51.6)84 (45.4)99 (46.5)138 (39.1)354 (43.4)BSA (0-100), mean (SD)10.1 (18.3)9.5 (16.8)8.5 (14.9)8.1 (14.6)8.7 (15.5)Physician assessed global health (NRS 0-10), mean (SD)6.3 (1.5)5.6 (1.8)5.2 (1.7)4.9 (1.9)5.2 (1.9)TJC68, mean (SD)9.9 (7.1)8.6 (7.6)8.2 (7.6)7.3 (8.2)8 (7.8)SJC66, mean (SD)6 (5.2)4.8 (4.9)4.7 (4.4)4.3 (3.8)4.6 (4.4)DAPSA, mean (SD)29.3 (11.1)25.1 (12.9)23.4 (12.1)18.9 (12.4)22.3 (12.8)DAS28-CRP, mean (SD)4.1 (1)3.8 (1.2)3.7 (1.1)3.2 (1.1)3.6 (1.2)Patient assessed global health (NRS 0-10), mean (SD)7.9 (2.1)6.6 (2.1)5.9 (2)4.8 (2.3)5.7 (2.4)Patient assessed pain (NRS 0-10), mean (SD)7.8 (1.8)6.4 (2.1)5.8 (2)4.6 (2.4)5.5 (2.4)DLQI (0-30), mean (SD)8.5 (8.2)7.8 (7.2)5.4 (5.7)4.1 (4.9)5.6 (6.2)PSAID (0-10), mean (SD)6.9 (1.8)5.5 (1.8)4.4 (1.7)3 (1.7)4.2 (2.2)Conclusion:The impact of depressive symptoms on outcome parameters used in rheumatology is increasingly being recognised. Interestingly, direct measures of inflammatory disease activity of joint and skin disease such as BSA, CRP, and swollen joint count were not correlated with depressive symptoms. The highest correlation was found for broader assessments like global health status and PSAID.References:[1]Haugeberg et al. Arthritis research & Therapy, 2020, 22:198Acknowledgements:RABBIT-SpA is supported by a joint, unconditional grant from AbbVie, Amgen, Biogen, Hexal, Janssen-Cilag, Lilly, MSD, Novartis, Pfizer, UCB and Viatris.We thank all participating rheumatologists and patients.Disclosure of Interests:Anne Regierer Grant/research support from: AbbVie, Amgen, Biogen, Hexal, Janssen-Cilag, Lilly, MSD, Novartis, Pfizer, UCB and Viatris., Anja Weiß Grant/research support from: AbbVie, Amgen, Biogen, Hexal, Janssen-Cilag, Lilly, MSD, Novartis, Pfizer, UCB and Viatris., Martin Bohl-Buehler: None declared, Xenofon Baraliakos: None declared, Frank Behrens: None declared, Georg Schett: None declared, Anja Strangfeld Grant/research support from: AbbVie, Amgen, Biogen, Hexal, Janssen-Cilag, Lilly, MSD, Novartis, Pfizer, UCB and Viatris.

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Objectives:To analyze the effect of disease-modifying antirheumatic drugs (DMARDs) and identify risk factors associated with disease progression and mortality in patients with rheumatoid arthritis associated with interstitial lung disease (RA-ILD).Methods:We performed a multicenter, prospective, observational study of patients with RA-ILD receiving DMARDs between 2015 and 2020. The patients were assessed using high-resolution computed tomography and pulmonary function tests at baseline and at 60 months. The main outcome measure at 60 months was worsening of FVC >10% or DLCO >15% and radiological progression or death. We recorded demographic and clinical characteristics, lung function, and the incidence of adverse events. A Cox regression analysis was performed to identify factors associated with worsening of ILD.Results:After 60 months, lung disease had stabilized in 66 patients (56.9%), improved in 9 (7.8%), and worsened in 23 (19.8%). Eighteen patients (15.5%) died, with a mean survival of 71.8 (1.9) months. Baseline characteristics of 116 with RA-ILD treated with DMARDs is in table 1.The Cox multivariate analysis revealed the independent predictors of worsening of RA-ILD to be usual interstitial pneumonia (HR, 2.6 [95%CI, 1.0-6.7]), forced vital capacity (%) (HR, 3.8 [95%CI, 1.5-6.7]), anticitrullinated protein antibody titers (HR, 2.8 [95%CI, 1.1-6.8]), smoking (HR, 2.5 [95%CI, 1.1-6.2]), and treatment with abatacept, tocilizumab, or rituximab (HR, 0.4 [95%CI, 0.2-0.8]). During follow-up, 79 patients (68%) experienced an adverse event, mostly infection (61%).Conclusion:Lung function is stable in most patients with RA-ILD receiving treatment with DMARDs, although one third of patients die. Identifying factors of worsening in RA-ILD is important for clinical management.Table 1.Baseline characteristics of 116 with RA-ILD treated with DMARDsVariableTotal=116Epidemiological characteristicsFemale sex, n (%)63 (54.3)Age, years, mean (SD)68.3 (9.9)Clinical and analytical characteristicsCurrent smokerNonsmoker, n (%)57 (49.1)Smoker, n (%)23 (19.8)Exsmoker, n (%)36 (31.0)Time since diagnosis of RA, months, median (p25-p75)148.5 (71.5-217.8)Diagnostic delay, months, median (p25-p75)8.5 (4.9-16.8)Time since diagnosis of ILD, months, median (p25-p75)27.5 (9.8-60.0)Positive rheumatoid factor (>10), n (%)111 (95.7)Positive ACPA titer (>20), n (%)100 (86.2)Erosive disease, n (%)76 (65.5)Treatment Synthetic DMARD100 (86.2) Methotrexate, n (%)51 (44.0) Leflunomide, n (%)30 (25.9) Sulfasalazine, n (%)9 (7.8) Hydroxychloroquine, n (%)21 (18.1)Biologic DMARD50 (43.1) Infliximab, n (%)1 (0.9) Etanercept, n (%)6 (5.2) Adalimumab, n (%)3 (2.6) Golimumab, n (%)3 (2.6) Certolizumab, n (%)3 (2.6) Tocilizumab, n (%)6 (5.2) Abatacept, n (%)15 (12.9) Rituximab, n (%)13 (11.2) Immunosuppressants11 (9.5) Mycophenolate, n (%)7 (6.0) Azathioprine, n (%)4 (3.4) Antifibrotic agents, nintedanib, n (%)1 (0.9) Baseline corticosteroids, n (%)69 (60.0) Dose of baseline corticosteroids, median (p25-p75)5.0 (0.0-7.5)Abbreviations. RA: rheumatoid arthritis; ILD: interstitial lung disease; ACPA: anticyclic citrullinated protein antibody; DMARD: disease-modifying antirheumatic drug; SD: standard deviation.Acknowledgements:Grant for Medical Researchers of the “Fundación Española de Reumatología” 2019. declare.Disclosure of Interests:None declared

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Background:Infections are one of the main complications among patients with rheumatoid arthritis (RA) with immunosuppressive treatment. The differences between treatments and the influence of other factors is unclear.Objectives:To evaluate the frequency and factors associated with serious infections in patients with RA treated with biological therapy (BT) and JAKi and the differences between treatments.Methods:Descriptive and retrospective study (January 2015-December 2020) of patients with RA treated with BT (TNFi, non-TNFi) and JAKi (tofacitinib, bariticinib, upadacitinib) in a single center. Severe infection was considered a life-threatening infection or one that required hospitalization and intravenous treatment. Epidemiological variables, clinical characteristics, Charlson comorbidity index, type of BT or JAKi and concomitant treatment were collected.For the analysis frequencies and percentages are used in qualitative variables and mean ± SD in the quantitative ones. Statistical analysis was performed with IBM SPSS v 23.Results:We registered 257 patients (84.4% women) mean aged 56.1±13.4 years. RF was positive in 86.8%, anti-CCP in 75.9% and 16.5 % presented extra-articular manifestations (nodulosis 9.7%, intersticial lung disease 4.3%, other 1.5%). At the start of the study, 157 (61.1%) patients were with TNFi, 80 (31.1%) with non-TNFi and 20 (7.8%) with JAKi. Conventional synthetic DMARDs (csDMARDs) were used in 86% of cases (methotrexate 71.1%, leflunomide 21.2%, other 7.7%).During the study, 162 (63%) patients continued with the same treatment and in 95 (37%) it was changed at least once. 3 patients discontinued the treatment. At the end of the study, 126 (49%) patients were with TNFi, 81 (31.5%) with non-TNFi and 47 (18.3%) with JAKi.Severe infection was developed in 28 (10.9%) patients (13 respiratory, 5 urinary, 5 cellulitis, 4 sepsis, 1 osteomyelitis) among them 2 patients had severe infection and herpes zoster at the same time and 3 developed a second infection. 14 (50%) patients were with TNFi, 8 (28.6%) with non-TNFi and 6 (21.4%) with JAKi. Table 1The inflammatory activity of RA was mild at the time of infection (DAS28: 2.6±1.1). The median time until infection was: TNFi 45.25 [4.9-202.3] months, non- TNFi 19.14 [4.9-72.5] months and JAKi 17.63 [1.1-29.2] months.The Charlson index, concomitant use of glucocorticoids (GCC) at lower doses than 10mg/d, chronic obstructive pulmonary disease (COPD), diabetes (DM), moderate-severe renal insufficiency, congestive heart failure (CHF) and peripheral vascular disease were statistically significantly associated with infection. Table 1.TABLE 1.CHARACTERISTICS OF PATIENTS WITH INFECTION VS. WITHOUT INFECTIONINFECTIONYES n:28NO n:229pFEMALE, n (%)22 (78.6)195 (85.2)0.406AGE years, (mean±SD)57.7 ± 13.955.9 ± 13.40.507AGE ≥ 65 n (%)10 (35.7)68 (29.7)0.513RF +, n (%)25 (89.3)198 (86.5)0.677ANTI-CCP +, n (%)21 (75)174 (75.1)1.00ILD, n (%)1 (3.5)10 (4.3)0.809ALCOHOL, n (%)3 (10.7)17 (7.4)0.465SMOKER, n (%)10 (35.7)60 (26.2)0.244COPD, n (%)7 (25)24 (10.5)0.026*DM, n (%)7 (25)19 (8.3)0.013*CHF, n (%)4 (14.3)1 (0.4)0.001*RENAL INSUFFICIENCY, n (%)3 (10.7)2 (0.9)0.010*PERIPHERAL VASCULAR DISEASE, n (%)9 (32.1)22 (9.6)0.002*CHARLSON INDEX (mean±SD)1.64 ± 2.10.63 ± 1.20.001*TNFi, n (%) NON-TNFi n (%) JAKi, n (%)14 (50)112 (48.9)8 (28.6)73 (31.9)6 (21.4)41 (17.9)csDMARDs, n (%)22 (78.6)159 (69.4)0.317GCC dose <10mg/d, n (%)17 (60.8)111 (48.5)0.007*Conclusion:In our study, 10.9% of patients with RA treated with BT or JAKi developed severe infection during 5 years of follow-up. Concomitant GCC therapy and comorbidity increased the risk of presenting this complication.Disclosure of Interests:None declared

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Abstract Irradiation of the C57BL/6NHsd mouse lung results in pulmonary fibrosis. An acute phase (days 1 to 28) following irradiation recognized by an inflammatory response is followed by a latent phase (day 28 to day 125) where lung appears normal. Fibrosis occurs from day 125 till death characterized by bone marrow stromal cell migration to and proliferation in lung and increased collagen deposition. To investigate the role of endothelial cells, C57BL/6NHsd female mice were irradiated to 20 Gy to the pulmonary cavity shielding the rest of the body. Lung was excised at serial times, endothelial cells separated and tested for expression of endothelial genes vWF, VEGF, FGF1, CCL13 and CTGF; inflammatory genes IL-6; IGFbp7 and genes associated with fibrosis including MnSOD, Nrf2, NfkB, TLR4 and TGF-B. Endothelial cells were separated by using antibodies to CD45, or PECAM and sorting using flow cytometry. RNA was extracted using Triazol and gene expression determined using Real Time Polymerase Chain Reaction (RT-PCR). In irradiated total lung there was significant increase in endothelial cell markers at all times, compared to nonirradiated lung. Transcripts for vWF increased by 474.1 ± 388.5% (p = 0.017) by 2 days after irradiation, 520 ± 55.4% (p < 0.0001) at day 50, and 484.8 ± 26.8% (p < 0.0001) by day 200. VEGF and CTGF also remained elevated. In contrast, total lung MnSOD gene expression increased by 140.6 ± 46.1% at day 2 (p = 0.0185), decreased at day 50 to 17.9 ± 11.2% (p = 0.2808), and increased to 31.5 ± 11.4% by day 200 (p = 0.023). However, purified endothelial cells compared to alveolar cells, showed increased expression of not only the endothelial cell genes but also MnSOD, Nrf2, NfkB, and TGF-B. MnSOD expression in endothelial compared to alveolar cells at day 28 after irradiation was higher at 244.5 ± 7.8 vs 80.5 ± 4.9 (p = 0.0016), at day 150 expression was 140.1 ± 25.0 vs 5.4 ± 1.2 (p < 0.0001) and day 200 expression was 368.5 ± 6.4 vs 51.8 ± 10.3 (p = 0.0007). Lung endothelial cells display critical biomarkers of irradiation injury leading to fibrosis. Disclosures: No relevant conflicts of interest to declare.

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Abstract Introduction: Since its implementation in 2012, the IPSS-R (Greenberg et al., 2012), defines the latest standard in risk stratification of patients with Myelodysplastic Syndromes (MDS). However, the prognostic impact of rare abnormalities remains unclear as yet because the number of these aberrations was too low to allow a valid statistical analysis. Hence, rare abnormalities were coalesced in one group in the IPSS and IPSS-R and, due to the unknown prognosis of these abnormalities, classified as prognostically intermediate. The main goal of the study presented here was to analyse the type, frequency and prognosis of rare single abnormalities in a large cohort of patients with primary, untreated MDS and integrate them in the existing IPSS-R in order to refine its predictive power. Methods: The data set analyzed was derived from the IPSS-R database and extended by additional data from European centers. In total, 7245 patients with primary, untreated MDS were included. Of these, we identified 410 (6%) pts. with rare single abnormalities. An aberration was defined as rare when it occurred in less than 10 patients in the cytogenetic scoring system that was the basis for the IPSS-R (Schanz et al., 2012). Additionally, further cytogenetic abnormalities not considered in this score were detected. A specific cytogenetic subgroup was defined as having at least n=5 cases with the same abnormality. Survival analyses was performed in cytogenetic subgroups with a minimum number of n=10 exclusively. The participating centers (in numerical order) were: Spain (n=110; 26.8%), MD Anderson Cancer Center (69; 16.8%), Düsseldorf (44; 10.8%), IMRAW (41; 10.0%), France (32; 7.8%), Pavia (21; 5.1%), Vienna (19; 4.6%), Japan (13; 3.2%), Vienna Medical University (12; 2.9%) Italy (11; 2.7%), Cleveland (10; 2.4%), Dundee (9; 2.2%), Brazil (8; 2.0%), Netherlands (5; 1.2%), Czech (2, 0.5%), Freiburg (1; 0.2%), Innsbruck (1; 0.2%), Sweden (1; 0.2%), and Russia (1; 0.2%). The median overall- (OS) and AML-free survival (AFS) was calculated for any specific cytogenetic subgroup. Results: Rare single abnormalities detected were: der(1;7)(n=24; 5.9%), partial or total monosomy 13 (22; 5.4%), partial or total monosomy 9 (22; 5.4%), +21 (20; 4.9%), +mar (14; 3.4%), del(3p) (12; 2.9%), total or partial monosomy 21 (11; 2.7%), total or partial monosomy X (11; 2.7%), total or partial monosomy 18 (10; 2.4%), +1/+1q (10; 2.4%), del(17p) (9; 2.2%), total or partial monosomy 14 (9; 2.2%), total or partial monosomy 16 (9; 2.2%), total or partial monosomy 6 (9; 2.2%), total or partial monosomy 1 (8; 2.0%), t(11q23;varia) (7; 1.7%), total or partial monosomy 19 (6; 1.5%), +11/+11q (6; 1.5%), +13 (6; 1.5%), +14 (6; 1.5%), del(5p) (5; 1.2%), total or partial monosomy 2 (5; 1.2%), +15 (5; 1.2%) and +X (5; 1.2%) The remaining 159 patients (38.7%) showed very rare abnormalities occurring in less than 5 patients each. The median overall survival as well as the AML-free survival in each category will be presented in detail. Furthermore, a multivariate model including all relevant confounders and a proposal to integrate these abnormalities in the cytogenetic module of the IPSS-R will be suggested. Conclusions: In order to overcome the problem of their extremely low frequency, knowledge about rare single abnormalities in MDS can only be gained by large, international cooperative projects. The present study was performed to identify and comprehensively analyze rare abnormalities occurring in MDS, uninfluenced by therapy or additional abnormalities. The results will lead to a further refinement of the cytogenetic prognostic classification in patients with MDS. The study was supported by a grant from the European Leukemia Net (ELN) Disclosures Schanz: Novartis: Honoraria, Other: Travel Grant; Celgene: Honoraria, Research Funding; Alexion: Other: Travel Grant; Lilly: Other: Travel Grant. Sole:Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees. Fenaux:Amgen: Honoraria, Research Funding; Celgene Corporation: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Novartis: Honoraria, Research Funding. Valent:Novartis: Consultancy, Honoraria, Research Funding; Ariad: Honoraria, Research Funding; Bristol-Myers Squibb: Honoraria; Pfizer: Honoraria; Celgene: Honoraria. Ohyashiki:Kyowa Kirin KK: Honoraria; Novartis Pharma KK: Honoraria, Research Funding, Speakers Bureau; Celegen KK: Consultancy, Honoraria, Research Funding, Speakers Bureau; Jansen Pharma KK: Honoraria, Research Funding, Speakers Bureau; Chugai Pharna KK: Research Funding; Bristol Meyer Squib KK: Research Funding; Taiho Yakuhin KK: Research Funding; Asahikasei: Research Funding; Teijin Pharma KK: Research Funding; Alexion Pharma KK: Research Funding; Asteras: Research Funding; Shinbaio Pharma KK: Honoraria; Toyama Kagaku KK: Speakers Bureau; MSD KK: Honoraria; Nippo Shinyaku KK: Speakers Bureau; Sumitomo Dainippon: Membership on an entity's Board of Directors or advisory committees. Sekeres:Celgene Corporation: Membership on an entity's Board of Directors or advisory committees; TetraLogic: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees.

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Background:Juvenile idiopathic arthritis (JIA) can cause considerable pain and disability in childhood and adulthood. The number of studies exploring the efficacy of medications in adult JIA patients is limited. Methotrexate (MTX) is a commonly used medication for this patient group.Objectives:To explore the effects of MTX monotherapy (mono) on disease activity in adult patients diagnosed with JIA, compared to a weighted rheumatoid arthritis (RA) cohort.Methods:Data from NOR-DMARD, a longitudinal observational study enrolling patients > 18 years starting or switching DMARD treatment for inflammatory joint disease, was used [1]. Patients starting MTX mono treatment, and with a clinical diagnosis of JIA or other inflammatory arthropathies diagnosed before the age of 16 years, were identified from the study population. RA patients starting the same treatment regimen were included for comparative purposes.Disease activity measurements and remission rates were collected at baseline, 3 and 6 months. Changes in disease activity and absolute remission rates after 3 and 6 months were calculated. Remission rates and change in disease activity from baseline were compared between JIA patients and a weighted RA cohort with weights based on age and gender, using linear and logistic regression for continuous and categorical variables, respectively.Results:2201 patients were included in the analyses, 101 JIA patients (80.2% female, mean (SD) age 35.6 (13.0) years, mean (SD) diagnosis duration 24.8 (12.9) years), and 2100 RA patients (69.4% female, mean (SD) age 56.6 (13.6) years, mean (SD) diagnosis duration 4.1 (8.1) years) were included in the analyses. Age, gender distribution and disease duration differed significantly between cohorts.Both the JIA and RA group improved significantly across all disease activity measures from baseline to 3 and 6 months (Table 1). Both groups had a progressive increase in remission rates from baseline to 6 months (Table 1, Figure 1). The RA group had a significantly greater improvement in ESR after 3 months, SJC28 after 6 months and TJC28, DAS28, SDAI and MHAQ after 3 and 6 months. There were no significant group differences in remission rates.Table 1.BaselineChange to 3 monthsChange to 6 monthsJIA*RA*Diff.§JIA*RA*Diff.§JIA*RA*Diff.§ESR, mm/h20.4 (18.2)28.7 (22.2)3.7 (-0.6 to 8.1)-3.1 (15.8)-9.6 (18.7)-5.7 (-10.1 to -1.4)-3.0 (17.5)-11.3 (19.8)-5.4 (-10.8 to 0.03)SJC283.9 (4.8)6.9 (5.7)2.0 (0.9 to 3.2)-1.8 (3.3)-3.5 (5.5)-0.9 (-1.9 to 0.02)-1.8 (3.3)-4.2 (5.6)-1.5 (-2.6 to -0.5)TJC 284.5 (4.9)8.0 (7.1)3.1 (1.9 to 4.2)-0.8 (4.2)-3.5 (7.4)-1.9 (-3.1 to -0.7)-1.4 (3.8)-4.0 (6.8)-2.3 (-3.4 to -1.1)DAS284.0 (1.3)4.9 (1.3)0.6 (0.2 to 0.9)-0.6 (1.2)-1.2 (1.5)-0.5 (-0.9 to -0.2)-0.7 (1.2)-1.4 (1.5)-0.6 (-1.0 to -0.2)SDAI18.3 (11.3)26.0 (13.6)5.6 (2.7 to 8.4)-6.0 (9.7)-11.0 (14.0)-3.1 (-5.9 to -0.2)-6.3 (8.2)-12.8 (14.2)-5.1 (-7.8 to -2.2)PGA51.0 (24.6)48.3 (24.3)-4.5 (-10.0 to 1.1)-13.2 (25.3)-14.7 (26.5)-1.0 (-7.4 to 5.3)-11.3 (23.8)-14.3 (26.7)-4.6 (-11.9 to 2.7)MHAQ0.5 (0.5)0.7 (0.5)0.1 (-0.05 to 0.2)-0.2 (0.3)-0.2 (0.5)-0.1 (-0.2 to -0.0)-0.1 (0.3)-0.2 (0.5)-0.16 (-0.3 to -0.1)*Mean (SD)§ Weighted group difference, RA coefficient (95 % confidence interval)Figure 1.Mean 3- and 6-month remission rates with error bars (SE)Conclusion:Adult JIA patients had significant improvement across all the presented disease activity measures 3 and 6 months after treatment initiation with MTX mono. The magnitude of improvement was smaller than in the RA group, but JIA patients obtained remission at similar rates as RA patients.References:[1]Kvien, T.K., et al., A Norwegian DMARD register: prescriptions of DMARDs and biological agents to patients with inflammatory rheumatic diseases. Clin Exp Rheumatol, 2005. 23(5 Suppl 39): p. S188-94.Disclosure of Interests:Imane Bardan: None declared, Karen Minde fa*gerli: None declared, Joe Sexton: None declared, Gunnstein Bakland Speakers bureau: Abbvie, Consultant of: UCB, Pfizer, Novartis, Pawel Mielnik: None declared, Liz Marina Paucar Loli: None declared, Tore K. Kvien Speakers bureau: Amgen, Celltrion, Egis, Evapharma, Ewopharma, Hikma, Oktal, Sandoz and Sanofi, Consultant of: AbbVie, Amgen, Biogen, Celltrion, Eli Lilly, Gilead, Mylan, Novartis, Pfizer, Sandoz and Sanofi, Grant/research support from: AbbVie, Amgen, BMS, MSD, Pfizer and UCB, Eirik kristianslund: None declared, Anna-Birgitte Aga Grant/research support from: Dr. Aga reports personal fees from Abbvie, Eli Lilly, Novartis and Pfizer, outside the submitted work

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Maddox Dairy, located in Riverdale, CA, USA, is a Holstein herd that milks 3500 cows with a 305-day mature-equivalent milk production of 12 800 kg, and they have been producing high genetic animals by embryo transfer (ET) since the early 1980s. Invivo-derived embryos from Holstein donors were transferred fresh (grade 1 or 2) or frozen (grade 1), at morula (4), early blastocyst (5), or blastocyst (6) stage, to virgin heifers (VH, natural oestrus, 13-15 months old) or lactating cows (LC, Presynch-Ovsynch, 86 days in milk, first or second lactation) 6 to 9 days after oestrus. Pregnancy diagnosis was done by transrectal ultrasonography at 32-46 days in VH and by the IDEXX PAG test at 30 days in LC. June, July, August, September, and October were called critical months (first service AI conception rate drops below 44%) and compared with the other months. The data from 32 503 ETs between January 2008 and December 2018 are summarised on Table 1. Pregnancy rates (PR) are lower for LC recipients than for VH. Embryo transfers performed 7 or 8 days after oestrus had higher PR in both types of recipients and embryos, but Day 6 and 9 oestrus are also used with fair results. The season does not seem to affect PR. There is not enough difference in the combination of stage and days from oestrus for invivo-derived embryos. These numbers do not belong to a planned experiment. Several management changes during the years were made, which make it very difficult to apply statistical methods to analyse the data correctly. They are used as a tool to make decisions in an attempt to improve future results. Table 1.Pregnancy rate (PR) of virgin heifers (top) and lactating cows (bottom)-fresh (SH) and frozen (OZ) invivo-derived embryo transfer1 Heat-months SH-ST4 SH-ST5 SH-ST6 SH-All OZ-ST4 OZ-ST5 OZ-ST6 OZ-All PR% n PR% n PR% n PR% n PR% n PR% n PR% n PR% n Heifers 6 d-CM 62 934 66 243 68 69 63 1246 56 473 58 219 62 42 57 734 6 d-OM 62 1623 67 489 69 211 64 2323 56 600 55 296 48 137 55 1033 6 d-T 62 2557 67 732 69 280 63 3569 56 1073 57 515 51 179 56 1767 7 d-CM 64 1506 68 495 67 221 65 2222 60 822 62 340 63 156 61 1318 7 d-OM 66 2723 68 1021 69 510 67 4254 57 1120 59 581 57 231 58 1932 7 d-T 66 4229 68 1516 69 731 67 6476 58 1942 60 921 60 387 59 3250 8 d-CM 65 1348 64 518 67 322 65 2188 59 595 64 258 63 108 61 961 8 d-OM 66 2166 68 886 70 510 67 3562 61 770 60 364 51 130 60 1264 8 d-T 66 3514 67 1404 69 832 66 5750 60 1365 62 622 56 238 60 2225 9 d-CM 60 109 56 43 70 20 60 172 60 5 33 6 50 4 47 15 9 d-OM 58 129 63 57 60 40 60 226 63 16 50 18 75 4 58 38 9 d-T 59 238 60 100 63 60 60 398 62 21 46 24 63 8 55 53 All-CM 64 3897 66 1299 67 632 65 5828 58 1895 61 823 63 310 60 3028 All-OM 65 6641 67 2453 69 1271 66 10 365 58 2506 58 1259 53 502 58 4267 All-T 65 10 538 67 3752 69 1903 66 16 193 58 4401 60 2082 57 812 59 7295 Lactating cows 6 d-CM 54 265 48 86 50 12 53 363 38 141 31 77 50 10 36 228 6 d-OM 49 463 52 203 45 56 50 723 46 101 48 54 59 27 48 182 6 d-T 51 728 51 289 46 68 51 1086 41 242 38 131 57 37 42 410 7 d-CM 54 755 59 274 56 103 55 1137 43 928 48 450 43 192 45 1570 7 d-OM 55 914 66 367 54 109 58 1393 46 1052 45 564 47 353 46 1969 7 d-T 55 1669 63 641 55 212 57 2530 45 1980 46 1014 46 545 45 3539 8 d-CM 63 252 68 82 76 33 65 368 48 219 56 80 42 33 50 332 8 d-OM 61 257 64 161 53 47 61 466 50 191 53 77 56 16 51 284 8 d-T 62 509 65 243 63 80 63 834 49 410 55 157 47 49 50 616 All-CM 56 1272 58 442 60 148 57 1868 44 1288 47 607 43 235 45 2130 All-OM 55 1634 62 731 51 212 56 2582 47 1344 46 695 48 396 47 2435 All-T 55 2906 60 1173 55 360 57 4450 45 2632 47 1302 46 631 46 4565 1ST=stage; CM=critical months (June, July, August, September, and October); OM=other months.

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The aimof this study was to identify predictors of poor outcomes in patients hospitalized for severe acute exacerbation of COPD (AECOPD).Methods. This retrospective, observational cohort study was conducted in Pulmonology Department of a city hospital in 2015 – 2016 and involved patients hospitalized for severe AECOPD. Patients were divided according to outcomes. Poor outcomes included at least one of the followings: the need in invasive (IMV) or non-invasive (NIV) ventilation, admission to ICU, in-hospital death and COPD- related readmission during 2 months. Demographic, clinical, laboratory parameters, pulmonary function tests and blood gas analysis were analyzed; different multidimensional prognostic scores were also evaluated and compared.Results. Of 121 patients included, a poor outcome had occurred in 45 patients (37%). Among them, NIV was required in 21 (17%), IMV in 8 (6%), and admission to ICU in 16 patients (13%); death was registered in 6 patients (5%) and readmission in 27 (22%) of the patients. Patients with poor outcomes were admitted more frequently by ambulance (62% vs 40%; p = 0.003), more often were admitted to a hospital for AECOPD in the previous year (69% vs 45%; p = 0.0006), and had lower pH (p = 0.001), lower PaO2 (p = 0.001), higher PaCO2 (p = 0.001), and a worse score on several prognostic scales such as APACHE II (13.9 ± 5.4 vs 7.8 ± 3.6; p = 0.001), DECAF (2.4 ± 0.6 vs 1.5 ± 0.6; p = 0.001), BODEx (5.6 ± 1.8 vs 3.9 ± 1.1; p = 0.001), DOSE (2.9 ± 1.5 vs 2.2 ± 1.2; p = 0.029), and ADO (4.9 ± 1.5 vs 4.3 ± 1.3; p = 0.015) at admission. They more frequently received O2 therapy (87% vs 46%; p = 0.001) and had longer hospital stay (19.2 ± 6.2 days vs 12.5 ± 1.8 days; p = 0.001). Conclusions. Hypercapnia, hypoxemia and worse prognostic scores on admission predicted poor outcome in patients hospitalized for AECOPD during the previous year.

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Abstract Background: This study was designed to investigate the activity and safety of rituximab (Rituxan®, R) plus CHOP induction therapy followed by maintenance R in patients with previously untreated advanced stage indolent NHL. The initial results of R-CHOP induction treatment are reported here. Methods: 102 patients with Ann Arbor Stage III or IV indolent NHL (follicle center/follicular grade I/II or nodal marginal zone B-cell by REAL; Type B or C by IWF) were enrolled into this open-label, multi-center, community-based, Phase II, single-arm trial. Patients received 6 cycles of standard R-CHOP induction therapy (cyclophosphamide 750 mg/m2, vincristine 1.4 mg/m2, doxorubicin 50 mg/m2 all IV on Day 1; prednisone 100 mg/day Days 1–5). R 375 mg/m2 was given on Day 1 of each cycle except for cycle 1, when it was administered 2–3 days prior to CHOP chemotherapy. Subjects with an ongoing response (CR/CRu or PR) after induction receive maintenance R (4 weekly infusions) within 28 days after the completion of induction and repeated every 6 months for 2 years for a total of 16 maintenance R doses. The primary endpoints were CR/CRu after 6 cycles of induction and the incidence of R infusion-related toxicity during induction and maintenance therapy. Secondary endpoints included overall response rates (ORR), infusion times, serious adverse events (SAE) in induction and maintenance, and rituximab pharmaco*kinetics in maintenance therapy. Results: Baseline characteristics were: median age 57y (33.3% ≥60y); 40.2% female; ECOG performance status 0: 70.6%; Ann Arbor stage III: 28.4% and IV: 71.6%. Serum β2-microglobulin and LDH at baseline were above normal in 66.3% and 20.6%, respectively. CR/CRu at the end of induction in 102 patients was 51.0% (ORR 86.3%). 1% had progressive disease (PD) during induction. 2 subjects died during the induction period, both due to SAEs (probable pulmonary embolus, acute respiratory distress). SAEs occurred in 22.5% of subjects during induction with the most common event being febrile neutropenia (7.8%). Grade 3–4 R infusion-related toxicity occurred in 4.9% of patients in cycle 1; this decreased to 1% by cycle 2 of induction. Two subjects discontinued R for infusion-related toxicity. 44% of patients were able to receive their R dose within 3 hrs at cycle 2 and 69.2% of patients at cycle 6. Conclusion: Patients with advanced stage indolent NHL treated in the community setting with R-CHOP induction tolerate therapy well and have an excellent response rate. The outcomes of maintenance therapy and rituximab pharmaco*kinetics in maintenance await further follow-up.

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AbstractObjectiveTo evaluate differences in interstage growth of pulmonary arteries between use of polytetrafluoroethylene and femoral vein hom*ograft as Sano shunt during stage-I Norwood palliation.MethodsA retrospective review of all patients who survived to the second stage following Norwood–Sano operation at two institutions was performed. Either polytetrafluoroethylene or the valved segment of femoral vein hom*ograft was used for construction of the Sano shunt. The size of pulmonary arteries was compared at pre-Glenn catheterisation.ResultsA total of 48 neonates with the diagnosis of hypoplastic left heart syndrome or its variants comprised the study population. Femoral vein hom*ograft of 5–6 mm diameter was used in 14 and polytetrafluoroethylene graft of 5 mm was used in 34 patients. The two groups were comparable in terms of preoperative demographics and age at time of pre-Glenn catheterisation (3.9±0.7 versus 3.4±0.8 months, p=0.06). Patients who received femoral vein hom*ograft demonstrated a significantly higher pre-Glenn Nakata index [264 (130–460) versus 165 (108–234) mm2/m2, p=0.004]. The individual branch pulmonary arteries were significantly larger in the femoral vein group (right, 7.8±3.6 versus 5.0±1.2, p=0.014; left, 7.2±2.1 versus 5.6±1.9, p=0.02). There were no differences in cardiac index, Qp:Qs, ventricular end-diastolic pressure or systemic oxygen saturations.ConclusionsUtilisation of a valved segment of femoral vein hom*ograft as right ventricle to pulmonary artery conduit during Norwood–Sano operation confers better interstage growth of the pulmonary arteries. Further studies are needed to evaluate the impact of femoral vein hom*ograft on single ventricle function.

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Background. Goal-directed fluid therapy (GDT) guided by functional parameters of preload, such as stroke volume variation (SVV), seems to optimize hemodynamics and possibly improves clinical outcome. However, this strategy is believed to be rather fluid aggressive, and, furthermore, during surgery requiring thoracotomy, the ability of SVV to predict volume responsiveness has raised some controversy. So far it is not known whether GDT is associated with pulmonary fluid overload and a deleterious reduction in pulmonary function in thoracic surgery requiring one-lung-ventilation (OLV). Therefore, we assessed the perioperative course of extravascular lung water index (EVLWI) and -ratio during and after thoracic surgery requiring lateral thoracotomy and OLV to evaluate the hypothesis that fluid therapy guided by SVV results in pulmonary fluid overload.Methods. A total of 27 patients (group T) were enrolled in this prospective study with 11 patients undergoing lung surgery (group L) and 16 patients undergoing esophagectomy (group E). Goal-directed fluid management was guided by SVV (SVV < 10%). Measurements were performed directly after induction of anesthesia (baseline—BL), 15 minutes after implementation OLV (OLVimpl15), and 15 minutes after termination of OLV (OLVterm15). In addition, postoperative measurements were performed at 6 (6postop), 12 (12postop), and 24 (24postop) hours after surgery. EVLWI was measured at all predefined steps. The -ratio was determined at each point during mechanical ventilation (group L: BL-OLVterm15; group E: BL-24postop).Results. In all patients (group T), there was no significant change in EVLWI during the observation period (BL: 7.8 ± 2.5, 24postop: 8.1 ± 2.4 mL/kg). A subgroup analysis for group L and group E also did not reveal significant changes of EVLWI. The -ratio decreased significantly during the observation period (group L: BL: 462 ± 140, OLVterm15: 338 ± 112 mmHg; group E: BL: 389 ± 101, 24postop: 303 ± 74 mmHg) but remained >300 mmHg except during OLV.Conclusions. SVV-guided fluid management in thoracic surgery requiring lateral thoracotomy and one-lung ventilation does not result in pulmonary fluid overload. Although oxygenation was reduced, pulmonary function remained within a clinically acceptable range.

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Background:Four clinical phenotypes of IgG4-Related Disease (IgG4-RD) have been recently identified by Latent Class Analysis (LCA) - Pancreato/biliary (Group 1); Retroperitoneum/Aortitis (Group 2); Head-and-neck limited (Group 3); Mickulicz/Systemic (Group 4) - but the relevance of this classification for patient management remains unknown (1,2).Objectives:We aimed to assess whether clinical judgment can replicate LCA classification and to evaluate potential differences in epidemiological features, serological findings, and disease outcomes between disease phenotypes.Methods:The study included 179 patients. Four IgG4-RD experts were asked to classify a validation cohort of 40 patients according to published LCA derived phenotypes based on clinical judgment. Agreement between LCA and clinical clustering was calculated. To assess differences among disease phenotypes, the following variables were recorded on additional 139 patients: serum IgG4 and IgE; inflammatory markers; eosinophils; plasmablasts; IgG4-RD Responder Index (RI); history of atopy, diabetes, osteoporosis, relapses, and tumors; cumulative dose of glucocorticoids and use of rituximab.Results:Clinical judgment recapitulated LCA classification with strong agreement between IgG4-RD experts (κ= 0.841, p < 0.0005). Group 1 showed the highest levels of serum IgG4 and IgE. Group 2 and 4 had the lowest and highest IgG4-RD RI, respectively (Table 1). Increased cumulative doses of glucocorticoids and higher relapse rate were observed in Group 3 (Fig 1). A higher incidence of diabetes mellitus was observed in Group 1 and 4.Table 1Clinical and serological characteristics of patients cohort.Group 1(59 pts - 45%)Group 2(29 pts - 22%)Group 3(25 pts - 19%)Group 4(18 pts - 14%)P valueFemale n° (%)12 (20%)8 (28%)11 (44%)5 (28%)0.18Age67 (61-73)61 (56-70)52 (40-62)57 (51-62)<0.0001Serum IgG4 (mg/dL)331 (184-575)155 (49-258)150 (80-255)282 (166-460)0.0009IgG4-RD RI9 (6-9)6 (6-9)9 (6-12)9 (6-13)0.004Definite diagnosis n° (%)20 (34%)18 (62%)20 (80%)10 (55%)0.0008Probable diagnosis n° (%)1 (0.59%)0 (0%)1 (0.19%)1 (0.14%)0.6Possible diagnosis n° (%)38 (64%)10 (34%)4 (16%)7 (39)0.0003Emergency Department n° (%)37 (63%)14 (48%)7 (28%)10 (55%)0.03History of atopy n° (%)7 (12%)4 (14%)7 (28%)6 (23%)0.09ESR (mm/h)20 (8-39)40 (14-59)38 (14-54)12 (8-21)0.04CRP (mg/L)5 (2-8)10 (3-52)8 (3-28)3 (2-6)0.03Eosinophils (cell/mm3)200 (200-500)200 (100-275)300 (200-475)200 (100-500)0.3IgE (U/mL)283 (97-723)69 (28-264)120 (41-412)219 (54-657)0.02Plasmablast (cell/mL)1765 (627-4000)1890 (1020- 4000)2000 (370- 4780)2690 (140-5130)0.99Diagnostic delay (months)4 (2-9)7 (4-12)10 (3-18)11 (2-38)0.04Starting prednisone dose(mg, range)60 (37-70)50 (40-75)65 (40-90)40 (30-70)0.8Diabetes at disease onset10 (17%)1 (3%)2 (8%)2 (11%)0.09Figure 1.Relapse free survival of the four different IgG4-RD phenotypes.Conclusion:Clinical phenotypes of IgG4-RD reflect differences in epidemiological features and prognostic outcomes.References:[1]Bledsoe JR, Della-Torre E, Rovati L, Deshpande V. IgG4-related disease: review of the histopathologic features, differential diagnosis, and therapeutic approach. APMIS. 2018;126:459-476.[2]Wallace ZS, Zhang Y, Perugino CA, Naden R, Choi HK, Stone JH; ACR/EULAR IgG4-RD Classification Criteria Committee. Clinical phenotypes of IgG4-related disease: an analysis of two international cross-sectional cohorts. Ann Rheum Dis. 2019;78:406-412.Disclosure of Interests:Marco Lanzillotta: None declared, Emanuel Della Torre: None declared, Corrado Campochiaro Speakers bureau: Novartis, Pfizer, Roche, GSK, SOBI, Gaia Mancuso: None declared, Lorenzo Dagna Grant/research support from: The Unit of Immunology, Rheumatology, Allergy and Rare Diseases (UnIRAR) received unresctricted research/educational grants from Abbvie, Bristol-Myers Squibb, Celgene, Janssen, Merk Sharp & Dohme, Mundipharma Pharmaceuticals, Novartis, Pfizer, Roche, Sanofi-Genzyme, and SOBI., Consultant of: Prof Lorenzo Dagna received consultation honoraria from Abbvie, Amgen, Biogen, Bristol-Myers Squibb, Celltrion, Novartis, Pfizer, Roche, Sanofi-Genzyme, and SOBI.

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Abstract Background Esophageal cancer surgery with lymphadenectomy is known as a cause of weight loss during perioperative period, but the change of body composition is unclear. Methods The aim of study is to clarify the influence of body composition change after esophagectomy. 144 patients(51 cases without NAC and 93 cases with NAC: 98 cases with less than G2 perioperative complications and 46 cases with G2 or more perioperative complications: 36 cases with recurrence and 108 cases without recurrence were included) of esophageal cancer who underwent esophagectomy with lymphadenectomy from August 2011 to December 2016 and evaluated body composition examination before operation and after operation(1, 3, 6 month) were included in this study. We compared the change of body composition between with or without preoperative chemotherapy, postoperative complication, and recurrence. Results The weight loss rate at discharging hospital, 1,3,6 month after discharge for without NAC group/with NAC group was 3.3/3.8%, 7.8/6.8%, 10.1/9.2%, 11.1/9.1% (NS), and the lean body mass reduction rate was 4.1/4.5%, 7.1/6.6%, 6.5/6.7% (N.S.), 6.6/4.3% (P < 0.05). The weight loss rate for with less than G2 perioperative complication group/with G2 or more perioperative complication group was 2.9/4.9%(P < 0.01), 6.1/8.7%(P < 0.01), 8.4/12.1%(P < 0.01), 8.4/11.2%(P < 0.05), and the lean body mass reduction rate was 3.7/5.9%(P < 0.05), 5.9/9.0%(P < 0.01), 5.6/9.6%(P < 0.01), 4.4/5.5%(N.S.). And there was no significant differences of weight loss rate and lean body mass reduction rate at discharging hospital, 1,3,6 month after discharge between with recurrence group and without recurrence group. Conclusion Due to postoperative complications after esophagectomy, the rate of weight loss increased from hospital discharge to 6 months after discharge. Particularly, lean body mass was reduced within 3 months. So, we may have a strategy such as continuing enteral nutrition even after discharge for complicated cases. Disclosure All authors have declared no conflicts of interest.

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The hypothesis was that GnRH on Day 5 of a synchronized cycle in embryo transfer recipients would increase progesterone (P4) concentrations, embryo size, and fertility. Holstein and cross-bred Holstein heifers (n = 1562) were synchronized using a modified 5-day CIDR Co-Synch as follows: Day –8 CIDR inserted; Day –3 CIDR removed; prostaglandin F2α treatment; Day –2 second prostaglandin F2α; Day 0 gonadotropin-releasing hormone (G1, 100 μg of gonadorelin acetate) to induce ovulation. On Day 5.5, heifers were assigned in a completely randomised design to 1 of 2 treatments: Control (untreated) or GnRH (200 μg of gonadorelin acetate). Transfer of fresh in vitro-produced embryos was performed between d 6 and 8 after G1. Data collected from each heifer included embryo stage and quality, body condition score, technician, interval from G1 to transfer, and number of previous transfers. All heifers were evaluated by transrectal ultrasonography on Day 5, 33, and 62 and a subset of heifers was scanned on Day 12 (n = 718; to determine ovulation to treatment) and another subset on Day 33 (n = 296; 16-s video to determine embryo and amniotic vesicle size). Serum P4 was determined from a subset of heifers on Day 12 (n = 467). Fertility data were analysed by logistic regression (LOGISTIC procedure, SAS 9.4), whereas continuous outcomes were analysed by ANOVA (MIXED procedure). Ovulation to Day 5.5 gonadotropin-releasing hormone was 83.9% (302/360) in GnRH-treated heifers v. 3.3% (12/358) in Control (P < 0.001). Progesterone on Day 12 was greater in GnRH-treated heifers 7.2 ± 0.1 ng mL–1 v. Controls 6.0 ± 0.1 ng mL–1 (P < 0.001). There was an effect of embryo stage at Day 33 and 60 of pregnancy, with Stage 7 having greater P/ET than Stage 6 embryos. Treatment with GnRH did not alter pregnancy per embryo transfer with either embryo stage but decreased pregnancy loss in Stage 7 embryos, as shown in Table 1. Embryo size measured as crown-rump length (CRL) did not differ, as shown in Table 1. Similarly, amniotic vesicle volume (AVV) was not different between GnRH (549.1 ± 16 mm3) and Control (543.5 ± 14 mm3; P = 0.86), nor was there an interaction between treatment and embryo stage (P = 0.71). In addition, neither AVV (P = 0.22) nor CRL (P = 0.41) were associated with pregnancy loss between Day 33 and 60. In conclusion, treatment with GnRH on Day 5 resulted in increased P4 and a reduction in pregnancy loss in heifers receiving a Stage 7 embryo without changing conceptus size. Table 1.Pregnancies per embryo transfer (P/ET), crown-rump length (CRL), and pregnancy loss in embryo recipients receiving gonadotropin-releasing hormone (GnRH) on Day 5.5 v. control

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Abstract Background Endoscopic sleeve gastroplasty (ESG) is rapidly becoming established as a safe and effective means of achieving substantial weight loss via the transoral route. New ESG suture patterns are emerging. Our aim was to investigate whether superior weight loss outcomes can be achieved by using a unique combination of longitudinal compression sutures and “U”-shaped sutures. Methods This is a retrospective review of prospectively collected data of all patients undergoing ESG by a single operator in a single UK center. Results Between January 2016 and December 2017, 32 patients (23 female) underwent ESG; n = 9 cases were completed utilizing a commonly used triangular suture pattern (“no longitudinal compression”) and n = 23 cases were completed using our unique “longitudinal compression” suture pattern. In the no compression and compression groups, the mean ages were 45 ± 12 years and 43 ± 10 years, the median baseline weights were 113.6 kg (range 82.0 – 156.4) and 107 kg (range 74.0 – 136.0), and the median baseline body mass indexes (BMIs) were 35.9 kg/m2 (range 30.9 – 43.8) and 36.5 kg/m2 (range 29.8 – 42.9), respectively. After 6 months, body weight had decreased by 21.1 kg (range, 12.2 – 34.0) in the compression group (n = 7) versus 10.8 kg (range, 7.0 – 25.8) in the no compression group (n = 5) (P = 0.042). Correspondingly, BMI decreased by 7.8 kg/m2 (range, 4.9 – 11.2) and 4.1 kg/m2 (range, 2.6 – 7.2) in each group, respectively (P = 0.019). Total body weight loss (%TBWL) was greater in the compression group at 19.5 % (range, 12.9 – 30.4 %) compared to 13.2 % (range, 6.2 – 17.1 %) in the non-compression group (P = 0.042). No significant adverse events were reported in this series. Conclusion The technique of ESG is evolving and outcomes from endoscopic bariatric therapies continue to improve. We provide preliminary evidence of superior weight loss achieved through a modified gastroplasty suture pattern.

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Background The effects of inspiratory muscle training on plasma cytokines, C-reactive protein and the soluble apoptosis mediators Fas and Fas ligand in chronic heart failure are unknown. Design and methods Thirty-eight patients with chronic heart failure, age 57 ± 2 years, New York Heart Association classification II-III, were assigned to either a high intensity training group ( n = 15, age 53±2 years) exercised at 60% of sustained maximal inspiratory pressure, or a low intensity training group ( n = 23, age 59 ± 2 years), exercised at 15% of sustained maximal inspiratory pressure, three times per week for 10 weeks. Patients in the high intensity training group and low intensity training group were matched for age, sex and New York Heart Association functional class. Plasma levels of tumor necrosis factor (TNF)-α, soluble TNF receptor I, interleukin-6, C-reactive protein, soluble apoptosis mediators Fas and Fas ligand were measured at baseline and at post-inspiratory muscle training. Pulmonary function was assessed by spirometry, exercise capacity by a cardiopulmonary exercise test and the 6 min walk test, whereas dyspnea by the Borg scale after the 6 min walk test. Results High intensity training group improved inspiratory muscle strength (105.1 ± 4.9 vs. 79.8 ± 4.7 cmH2O, P < 0.001), sustained maximal inspiratory pressure (504.5 ± 39.7 vs. 312.5 ± 26.5cmH2O/s/103, P<0.001), forced vital capacity (98.9 ± 3.9 vs. 96 ± 3.3%, P<0.05), peak Vo2 (19.4 ± 1.2 vs. 17.3 ± 0.9 ml/kg per min, P<0.01), 6 min walk test distance (404.3 ± 11.9 vs. 378.2 ± 10.4 m, P<0.01) and dyspnea (8.0 ± 0.4 vs. 9.2 ± 0.4, P<0.01). Circulating TNF-α, soluble TNF receptor I, interleukin-6, C-reactive protein, soluble apoptosis mediators Fas and Fas ligand were not significantly altered. Low intensity training group increased only the inspiratory muscle strength (90.3 ± 5.9 vs. 80.2 ± 5cmH2O, P<0.01). Comparison between groups was significant for soluble TNF receptor I change (high intensity training group, 5.8 ± 0.49 vs. 6.1 ± 0.42; low intensity training group, 8.4 ± 0.6 vs. 7.8 ± 0.6, P<0.01). Conclusion A high intensity inspiratory muscle training program resulted in improvement in functional status of chronic heart failure patients compared with low intensity inspiratory muscle training. Improvement in exercise capacity was not associated with an anti-inflammatory effect, although a beneficial influence on soluble TNF receptor I was recorded. Possible reasons include inadequate level of muscle mass exercise and the low pretraining New York Heart Association class. Eur J Cardiovasc Prev Rehabil14:679-685 © 2007 The European Society of Cardiology

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Abstract We assessed humoral response to influenza vaccination (vacc) in two consecutive seasons 2003/2004 and 2004/2005 in 123 NHL patients. In season 03/04 50 patients (29 previously treated with chemotherapy - group A03/04 and 21 not treated - group B03/04) and 73 patients in season 04/05: 34 treated - A04/05, 39 not treated - B04/05 were vaccinated with trivalent subunit influenza vaccine. Antibody responses to influenza hemagglutinin (HI) and neuraminidase (NI) were determined in sera collected before vacc, after 1 month and after 6 months. One month after vacc geometric mean antibody titers (GMTs) of antiHI antibodies significantly increased (p<0.05) and mean fold increases (MFIs) ranged from 10.4 to 24.3 in A03/04, 10.9–11.7 in A04/05, 6.5–31.6 in B03/04 and 14.8–21 in B04/05, than fell after 6 months to 3.6–7.8 in A03/04, 3.7–4.4 in A04/05, 1.7–11.2 in B03/04 and 7.8–8.5 in B04/05. Prevacc protection rate, i.e. the number of subjects with the protective HI antibody titers >1:40, ranged from 3.4 to 10.3% in A03/04, 2.9-8.8% in A04/05, 0–4.6% in B03/04 and 0–5.1% in B04/05. After 1 month protection rates ranged from 78.1 to 87.5% in A03/04, 61.8–70.6% in A04/05, 73.3–93.3% in B03/04 and 66.7–74.4% in B04/05 and decreased after 6 months to 24.1–37.9% in A03/04, 32.4–35.3% in A04/05, 19–47.6% in B03/04 and 17.9–35.9% in B04/05. Response rates, i.e. the number of subjects with at least a 4-fold increase of antiHI antibody titers after vacc, ranged from 58.6–75.9% in A03/04, 50–67.6% in A04/05, 57.1–81% in B03/04 and 61.5–71.8% in B04/05. Six months after vacc it decreased to 17.2–34.5% in A03/04, 20.6–29.4% in A04/05, 19–38.1% in B03/04 and 15.4–33.3% in B04/05. In all patients’ groups, post-vacc antiNI GMTs were significantly higher (p<0.05) than pre-vacc. MFIs of antiNI antibodies 1 month after vacc ranged from 11 to 17.5 in A03/04, 4.1–9.4 in A04/05, 5.1–9.9 in B03/04 and 6.3–9.9 in B04/05, then fell to 2.9–6.9 in A03/04, 1.3–5.1 in A04/05, 3.4–4.9 in B03/04 and 2.8–3.6 in B04/05. In season 03/04 only hemagglutinin H1 antibody titers were significantly higher in CTR than in patients in contrast of season 04/05 when in patients the titers of H1, H3 and N1, N2, NB were significantly lower. We conclude that the response to influenza vaccine is similar in patients previously treated and not-treated with chemoterapy. It is highly immunogenic in NHL patients, but the level of specific antibodies is variable and may depend on immunogenecity of vaccine for actual season. After 6 months the antibody titers rapidly decline, thus the NHL patients may need the second dose of vaccine to maintain good protective level.

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Abstract Thromboembolism frequently occurs during acute lymphoblastic leukemia (ALL) therapy. We prospectively registered thromboembolic events during the treatment of 1772 consecutive Nordic/Baltic patients with ALL aged 1 to 45 years who were treated according to the Nordic Society of Pediatric Hematology and Oncology ALL2008 protocol (July 2008-April 2017). The 2.5-year cumulative incidence of thromboembolism (N = 137) was 7.9% (95% confidence interval [CI], 6.6-9.1); it was higher in patients aged at least 10 years (P &lt; .0001). Adjusted hazard ratios (HRas) were associated with greater age (range, 10.0-17.9 years: HRa, 4.9 [95% CI, 3.1-7.8; P &lt; .0001]; 18.0-45.9 years: HRa, 6.06 [95% CI, 3.65-10.1; P &lt; .0001]) and mediastinal mass at ALL diagnosis (HRa, 2.1; 95% CI, 1.0-4.3; P = .04). In a multiple absolute risk regression model addressing 3 thromboembolism risk factors, age at least 10 years had the largest absolute risk ratio (RRage, 4.7 [95% CI, 3.1-7.1]; RRenlarged lymph nodes, 2.0 [95% CI, 1.2-3.1]; RRmediastinal mass, 1.6 [95% CI, 1.0-2.6]). Patients aged 18.0 to 45.9 years had an increased hazard of pulmonary embolism (HRa, 11.6; 95% CI, 4.02-33.7; P &lt; .0001), and patients aged 10.0 to 17.9 years had an increased hazard of cerebral sinus venous thrombosis (HRa, 3.3; 95% CI, 1.5-7.3; P = .003) compared with children younger than 10.0 years. Asparaginase was truncated in 38/128 patients with thromboembolism, whereas thromboembolism diagnosis was unassociated with increased hazard of relapse (P = .6). Five deaths were attributable to thromboembolism, and patients younger than 18.0 years with thromboembolism had increased hazard of dying compared with same-aged patients without thromboembolism (both P ≤ .01). In conclusion, patients aged at least 10 years could be candidates for preemptive antithrombotic prophylaxis. However, the predictive value of age 10 years or older, enlarged lymph nodes, and mediastinal mass remain to be validated in another cohort.

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Abstract Background To address the question if pediatric CD patients responding to nutritional induction therapy can be maintained in remission on dietary therapy without the use of immunosuppressive drugs, we designed a prospective randomized trial (CD-HOPE) comparing cyclic exclusive enteral nutrition (EEN) to daily supplement over a 12 month period. Methods CD patients (6–17 years) who successfully completed at least 6 weeks of EEN with clinical remission (wPCDAI ≤12.5) were recruited in 21 sites of the French GETAID pédiatrique between 12.2014 and 09.2018. All drug therapy had to be stopped at least 4 weeks prior to inclusion. A total of 112 patients were screened with 100 patients randomized to group A cyclic EEN (100% of caloric requirement) every 8 weeks for 2 weeks or group B daily supplementary nutrition (25% of caloric requirement). Patient stratification according to age (&lt; 10 years or older) and previous drug exposure or not. EEN and the nutritional supplement were in form of MODULEN IBD®. Except for the two weeks of EEN in group A food access was not restricted. Primary objective was the comparison of relapse rates at 12 months (defined as a wPCDAI &gt;12.5 at two consecutive visits) between the two groups (log-rank test per protocol). Additional analyses were performed using a multivariate regression analysis and cox model. Results 49 CD patients were randomized to group A (cyclic EEN) and 51 to group B (daily supplement) with 43/49 and 44/51 newly diagnosed patients without any previous drug exposure. Baseline characteristics were comparable between the two groups. Median age was 12 and 13 years, group A and B respectively. At the final 12 months visits a total of 25/49 patients (group A) remained in remission without disease activation compared to 12/51 patients (group B) (p=0.004) with a hazard ratio of 0.48 (0.29–0.80) (p= 0.0051). Kaplan Maier survival remission rates are shown in figure 1. Mean fecal calprotectine levels showed no significant difference between the two groups (297, 399 and 469 at month 0, 3, and 12 visits in group A and 480, 606, and 283 at month 0,3, and 12 visits in group B). Mucosal healing at M12 months was achieved in 25/49 patients (group A) and 18/51 patients (group B), with a mucosal healing rate of 52% (group A) and 33% (group B). Both treatment arms showed a significant catch-up growth. Conclusion This is first trial indicating that children/adolescents with CD responding to EEN as induction therapy can be maintained on remission with a nutritional therapy without immunosuppressors/biologics. However, daily nutritional supplement with normal access to food was not successful with a relapse rate of 76%. This study was supported by an unrestricted grant from Nestlé Health Science and sponsored by APHP.

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Background: In Bangladesh, the Institute of Epidemiology, Disease Control and Research (IEDCR) reported the first COVID-19 positive patients in the country on March 8, 2020. The world health organization (WHO) declared a COVID-19 epidemic on March 11, 2020. The aim of this study was related to the situation and relation of tests, infested, recovered and death of people against COVID-19 of Bangladesh. The study was carried out from 8 March 2020 to 30 April 2021 (N=419 days) to observe the status of Bangladesh towards rampant COVID-19. Methods: The data of this research was collected from IEDCR, Directorate General of Health Services (DGHS), Ministry of Health and Family Welfare (MoHFW), and cross-checked with different newspapers and online news portals. Correlations were made using Spearman's rank correlation coefficient. Results: The total tests, infection, recovered and died were 5357294, 747761, 669995 and 11250; respectively in Bangladesh. The tests of COVID-19 were 1482, 69252, 244064, 460528, 409503, 362113, 397452, 389452, 436862, 454892, 424034, 392403 and 722848 in March to December, 2020 to January to April 2021; respectively in Bangladesh. The infestation of COVID-19 was 49, 7616, 39486, 98330, 92125, 73070, 50457, 44205, 57248, 58948, 21629, 11077 and 128555 in March to December, 2020 to January to April 2021; respectively in Bangladesh. The recovered of COVID-19 was 25, 135, 7904, 34845, 76517, 69452, 71600, 48658, 56099, 70367, 22285, 17140 and 150816 in March to December, 2020 to January to April 2021; respectively in Bangladesh. The death of COVID-19 was 6, 163, 472, 1198, 1264, 1125, 970, 666, 718, 938, 568, 277 and 2237 in March to December, 2020 to January to April 2021; respectively in Bangladesh. The maximum number of people infested and death in April, 2021. The positive correlation found between infested with tests and recovered with tests of April, 2021 by people where (R2= 0.5289, p<0.012 and 0.0000006 p<0.05) and the negative correlation found between tests with date and death with tests (R2= 0.2567, p<0.01 and 0.3614, p<0.01). All the Spearman correlation positive with moderate to strong relation between the variables at the 0.01 level in two-tailed and the total number was n=419. The mean Spearman correlation for tests was 0.31 (range 0.553 to 0.634), for infested was 0.35 (range 0.611 to 0.880), for recovered was 0.796 (range 0.634 to 0.799), for death was 0.808 (range 0.553 to 0.880). March to December 2020 and January to February 2021, not much less than April 2021. Conclusions: More people infested and died in April, 2021 than previous year. This study also indicated that there is moderate to strong relation among tests, infested, recovered and death with COVID-(2020-2021).

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691 Background: In metastatic renal cell carcinoma (mRCC), immune-oncology (IO), alone or in combination, (IO-IO or IO-TKI) has changed the therapeutic scenario. Few real-world data are available about safety and outcome after IO progression. Methods: Baseline characteristics, outcome data including progression-free survival (PFS) and toxicities were retrospectively collected from 162 eligible pts treated in 16 Italian referral centers adhering to the Meet-Uro group and progressing to IO. Results: 111 pts (68,5%) were treated after progression to IO. 142 (87.6%) pts received IO as second line, 5 pts as first line and 16 pts as further line. Subsequent therapy included cabozantinib (n = 79, 48.0%), everolimus (n = 11, 6.7%), sunitinib (n = 6, 3.7%) and others (n = 15, 9.25%). Median IO-PFS was 4 months (95%CI 3.1-4.8) with no difference in pts pretreated with pazopanib or sunitinib (4 months (95%CI 2.4-5.5) vs 3,9 months (95%CI 2.9-4.9) p = 0.5). PFS tends to be longer in pts reporting adverse events of any grade (5.03 (95%CI 3.8-6.1) vs 2,99 (95%CI 2.4-3.5) months p = 0.004) or without nephrectomy (4.1 vs 2.9 months p = 0.071). Median PFS, in pts treated post-IO, was 6.5 months (95%CI 5.1-7.8). In term of best response, 55 pts (49%) had stability of disease/partial response and 29 pts (26%) had progressive disease, for the other pts treatment is still ongoing. Pts with ECOG PS 0 at progression to IO, had longer PFS, 11 months (95%CI 5.7-17.5) as well as those treated with cabozantinib (7.6 months, 95%CI 5.2-10.1) compared to everolimus, (3.2 months, 95%CI 1.8-4.5) or other drugs (4.3 months, 95%CI 1.3-7.4) p = 0.001. All grade adverse events were reported in 83 pts (74%) with G3-G4 adverse events in 39 pts (35%). Median overall survival, from first line, was 41,1 months (95%CI 30.4-51.8). Conclusions: In our real world experience after progression to IO, most pts received VEGF-TKI and mTOR inhibitors that showed to be active and safe choices. Cabozantinib was associated with a longer mPFS.

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Abstract Background Exploratory laparotomy surgery is abdominal operations not involving the gastrointestinal tract or biliary system. The objective of our study is to answer three questions: (a) What is the risk of surgical site infection (SSI) after exploratory abdominal surgery? (b) What is the impact of SSI in the hospital length of stay and hospital mortality? (c) What are risk factors for SSI after exploratory abdominal surgery? Methods A retrospective cohort study assessed meningitis and risk factors in patients undergoing exploratory laparotomy between January 2013 and December 2017 from 12 hospitals at Belo Horizonte, Brazil. Data were gathered by standardized methods defined by the National Healthcare Safety Network (NHSN)/CDC procedure-associated protocols for routine SSI surveillance. 26 preoperative and operative categorical and continuous variables were evaluated by univariate and multivariate analysis (logistic regression). Outcome variables: Surgical site infection (SSI), hospital death, hospital length of stay. Variables were analyzed using Epi Info and applying statistical two-tailed test hypothesis with significance level of 5%. Results A sample of 6,591 patients submitted to exploratory laparotomy was analyzed (SSI risk = 4.3%): Hospital length of stay in noninfected patients (days): mean = 16, median = 6, std. dev. = 30; hospital stay in infected patients: mean = 32, median = 22, std. dev. = 30 (P < 0.001). The mortality rate in patients without infection was 14% while hospital death of infected patients was 20% (P = 0.009). Main risk factors for SSI: ügeneral anesthesia (SSI = 4.9%, relative risk – RR = 2.8, P < 0.001); preoperative hospital length of stay more than 4 days (SSI=3.9%, RR=1.8, P = 0.003); wound class contaminated or dirty (SSI = 5.4%, RR = 1.5, P = 0.002); duration of procedure higher than 3 hours (SSI = 7.1%, RR = 2.1, P < 0.001); after trauma laparotomy (SSI = 7.8%, RR = 1.9, P = 0.001). Conclusion We identified patients at high risk of surgical site infection after exploratory laparotomy: trauma patients from contaminated or dirty wound surgery, submitted to a procedure with general anesthesia that last more than 3 hours have 13% SSI. Patients without any of these four risk factors have only 1.2% SSI. Disclosures All authors: No reported disclosures.

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Background:Joint pain is the most prevalent symptom for sufferers of osteoarthritis (OA). Pharmacological management of OA is restricted by limited efficacy and considerable toxicity, with growing fears about opioid use.Objectives:To understand the current real-world prescribed drug treatment paradigm related to OA disease severity for patients in 5 EU countries; France, Germany, Italy, Spain and the UK.Methods:Data were drawn from the Adelphi OA Disease Specific Programme (2017-18), a point-in-time study of physicians and their patients. Physicians classified their patients as currently having mild, moderate or severe disease severity, and provided details on currently prescribed OA therapy and physician satisfaction with therapy, rated from very satisfied to very dissatisfied. Patients were excluded from these analyses if they suffered from back and neck OA only, and shoulder OA that had not been diagnosed by X-ray. Comparisons among disease severity groups were made using analysis of variance and chi-squared tests.Results:The study included 489 physicians (primary care physicians, rheumatologists, orthopaedists) reporting on 3596 of their OA patients: 24% mild (n=874), 53% moderate (n=1904), and 23% severe (n=818). Overall, 73% patients were prescribed at least one drug for their OA (65% of mild; 76% of moderate; 77% of severe patients [<0.001]). Paracetamol (34%) was the most commonly prescribed OA treatment. NSAIDs (31%) and opioids (27%) were also frequently prescribed treatments, and worsening severity was associated with an increase in opioid use (11% of mild; 26% of moderate, 47% of severe patients [<0.001]), but not NSAID (Table 1). The mean number of prescription medications increased (0.9 for mild; 1.4 for moderate; 1.6 for severe patients [<0.001]) and physician satisfaction with treatment decreased (86% for mild; 70% for moderate; 41% for severe [<0.001]) with worsening OA disease severity.Table 1.Prescribed treatment by physician-reported OA severityMild(n=874)Moderate(n=1904)Severe(n=818)Current class of medication prescribed for OA, n (%)Paracetamol186 (21.3)663 (34.8)313 (38.3)NSAIDs267 (30.5)605 (31.8)237 (29.0)Any opioid93 (10.6)501 (26.3)386 (47.2)Weak opioid82 (9.4)407 (21.4)255 (31.2)Strong opioid11 (1.3)99 (5.2)146 (17.8)Opioid + analgesic (combined)6 (0.7)15 (0.8)7 (0.9)Corticosteroid31 (3.5)150 (7.9)92 (11.2)Glycosaminoglycan50 (5.7)149 (7.8)62 (7.6)Viscosupplement12 (1.4)93 (4.9)42 (5.1)Number of currently prescribed drug classes, mean (SD)0.9 (0.8)1.4 (1.1)1.6 (1.2)Conclusion:Physicians reported decreasing satisfaction with treatment for their OA patients as disease severity increased, despite increasing use of opioids and numbers of classes of prescribed drugs.Disclosure of Interests:Philip G Conaghan Consultant of: AbbVie, BMS, Eli Lilly, EMD Serono, Flexion Therapeutics, Galapagos, GSK, Novartis, Pfizer, Speakers bureau: AbbVie, Eli Lilly, Novartis, Pfizer, Lucy Abraham Shareholder of: Pfizer, Employee of: Pfizer, Peita Graham-Clarke Shareholder of: Eli Lilly and Co, Employee of: Eli Lilly and Co, Lars Viktrup Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Joseph C Cappelleri Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Craig Beck Shareholder of: Pfizer, Employee of: Pfizer, Andrew G Bushmakin Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Niall Hatchell: None declared, Emily Clayton: None declared, James Jackson: None declared

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e16708 Background: SCAN measured global readiness to provide diagnostics and treatments for NET patients in terms of awareness, availability, quality and affordability. This analysis focused on patient and healthcare professional (HCP) awareness of NET diagnostics and treatments. Methods: During Sept-Nov 2019, NET patients and HCPs completed an online survey (available in 14 languages). Results: There were 2795 respondents from 68 countries across 6 continents (2359 patients/carers; 436 HCPs). Primary NETs were most often gastroenteropancreatic NETs (GEP NET; 71% [1408/1983]), particularly small intestinal (35% [690/1983]) or pancreatic (20% [402/1983]). Biopsy was the most well-known diagnostic option in the overall NET patient group (82% [1917/2325]), the GEP NET patient subgroup (83% [1156/1395]) and HCPs (94% [411/435]), followed by CT (all patients: 81% [1874/2325]; GEP NET: 80% [1118/1395]; HCPs: 86% [376/435]). More HCPs were aware of specialized diagnostics, such as 68Ga-DOTA PET CT (HCP 81% [353/435]) and chromogranin A (CgA; 79% [344/435]), than patients (all: 68% [1574/2325] & 62% [1451/2325], respectively; GEP NET: 69% [962/1395] & 67% [936/1395]). The vast majority of all patients (87% [1983/2275]), GEP NET patients (89% [1215/1363]) and HCPs (91% [392/431]) knew surgery was a treatment option. Somastatin analogues were recognised as a treatment option by 90% of HCPs (387/431), but only 75% of GEP NET patients (1019/1363) and 70% of all NET patients (1599/2275). Nearly a quarter of HCPs (22% [95/431]) and one-third of patients (all: 33% [755/2275]; GEP NET: 30% [409/1363]) had not heard of peptide receptor radionuclide therapy (PRRT). The majority of patients (all: 88% [2007/2273]; GEP NET: 89% [1213/1370]) and HCPs (93% [396/425]) were aware of conventional imaging, such as CT/MRI/ultrasound, being used for ongoing monitoring of NETs. Approximately a third of all NET patients and a quarter of HCPs were unware CgA (patients: 32% [723/2273]; HCPs: 22% [94/425]) or 68Ga-DOTA PET CT (patients: 29% [670/2273]; HCPs: 24% [102/425]) were ongoing monitoring tools. Similarly, CgA and 68Ga-DOTA PET CT were not recognized by 27% of GEP NET patients (364/1370 & 371/1370, respectively). Conclusions: Increased awareness of NET diagnostics and treatments, particularly newer, more specialized tools, amongst both HCPs and patients is required to ensure continued advancements and improvements in the global standard of care for NETs.

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Background:Since the beginning of 2020, the COVID-19 pandemic has caused a considerable amount of fear, worry and concern in the general population and among certain groups such as the elderly, healthcare providers and people with pre-existing conditions in particular. Our patients suffering from chronic inflammatory rheumatism (CIR), a group of autoimmune pathologies treated by immunosuppressant medication, are particularly concerned. Actions taken – particularly quarantine and its effects on the normal activities, habits or livelihoods of many people – also have a significant impact. There is little information on the impact of the lockdown in patients with CIR with data measured prospectively, in a standardized way, before and during the first lockdown period.Objectives:The objective of this ancillary study was to evaluate the psychological impact of the first lockdown period (anxiety, depression, sleep disorders, catastrophizing...) as well as the evolution of disease activity in patients suffering from CIR.Methods:At two French university hospitals, adult patients with rheumatoid arthritis (RA) according to the ACR-EULAR 2010 criteria, spondyloarthritis (SpA) fulfilling the ASAS 2009 criteria and psoriatic arthritis (PsA) according to the Caspar 2006 criteria were consecutively included in the Catastrophism in Chronic Inflammatory Rheumatism (CRIC) study from September 2019. Sociodemographic data, information on the disease and its treatments were collected as well as questionnaires on disease activity (DAS28, CDAI, BASDAI), function (HAQ), quality of life (SF12, EQ5D), anxiety and depression (HADS, GAD7), insomnia (ISI) and catastrophizing scores (PCS). These data were collected prospectively at baseline, 3, 6 and 12 months.In this ancillary study, data from patients with an assessment before and during lockdown were analyzed. Statistical analyses were descriptive with a paired Student’s T-test.Results:In all, 140 patients (49 RA, 69 SpA and 22 PsA) were evaluated before and during lockdown. The median age was 53.5 [44-63] years and 60.7% were women; 74 patients (53.2%) were professionally active and 102 (72.9%) were living as couples. The majority of patients (92.9 %) had a disease lasting more than 2 years. Concerning treatments, 63 (45%) were treated by bDMARD monotherapy, 40 (28.5%) by bDMARD+ csDMARD, 17 (12.1%) by csDMARD monotherapy and 2 patients by tsDMARD; 90.7% were not taking any corticosteroids and 8.6% were taking ≤5 mg/d; 30% were on NSAIDs.When comparing before and during lockdown, pain, tender joint count, swollen joint count, disease activity (CDAI, BASDAI) and function (HAQ, SF12 physical component) were similar. However, there was a significant improvement in psychological status, anxiety (HADS, GAD7), the mental component of SF12, catastrophizing and overall quality of life (EQ5D) (see Table 1 below).Conclusion:There are very few prospective, standardized data on the impact of lockdown in patients with CIR with an assessment before and during the first lockdown period. In patients with CIR, the first lockdown period had no impact on the activity of the disease and was well experienced psychologically with less anxiety and an improvement in quality of life.Table 1.Outcome (N)140 CIR: 49 RA, 69 SpA, 22 PsABefore lockdownMean (SD)During lockdownMean (SD)Mean change(SD)PPain VAS (138)39.4 (25.3)39.4 (25.0)-0.28 (27.1)NSTJC (57)4.0 (6.8)4.7 (4.4)0.7 (5.9)NSSJC (56)1.0 (2.6)1.6 (1.7)0.5 (2.4)NSCDAI (36)11.7 (1.4)12.3 (7.5)1.2 (8.7)NSBASDAI (84)4.7 (1.9)4.9 (2.0)0.14 (1.4)NSHAQ (135)0.72 (0.57)0.72 (0.53)0.03 (0.33)NSSF12 mental(136)32.7 (8.7)36.2 (8.4)3.46 (8.01)<0.0001GAD-7 (anxiety) (135)7.7 (5.5)5.0 (5.3)-1.73 (0.40)<0.0001HADS anxiety(137)8.5 (3.9)7.8 (3.9)-0.64 (2.91)0.0113EQ5D(139)0.55 (0.31)0.61 (0.29)0.06 (0.24)0.0078PCS (catastrophizing) (137)18.9 (13.3)15.9 (11.1)-3.10 (9.60)0.0003Disclosure of Interests:None declared

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Abstract Abstract 728 Background: LM, an antibody-drug conjugate (ADC), is designed to specifically kill CD56+ cancer cells and contains a potent maytansinoid cytotoxic agent (DM1) attached to a CD56-targeting antibody. MM shows CD56 expression in >70% of cases. LM has demonstrated single agent clinical activity and an acceptable safety profile in relapsed/refractory (rel/ref) MM patients. Preclinical studies showed enhanced anti-MM activity when LM was combined with Len/Dex. To further study the safety and efficacy of LM in combination with Len/Dex, a phase I study was conducted in rel/ref patients. This abstract reports updated results on the safety and efficacy of LM/Len/Dex and preliminary results on the pharmaco*kinetics (PK) and immunogenicity studies. Methods: Primary study objectives were to determine the safety, maximum tolerated dose (MTD), recommended phase 2 dose (RP2D), anti-MM activity and PK of LM in combination with standard oral (PO) doses of Len (25 mg po, daily on days 1–21) and Dex (40 mg po on D 1, 8, 15, and 22) in CD56+ rel/ref MM patients who have received at least 1 prior therapy. LM was given intravenously (IV) on D 1, 8, and 15 on a 28-day cycle. Dose escalation was conducted in new cohorts of patients to define the MTD, which was then further evaluated in a dose-expansion cohort. Adverse events (AEs) were assessed using CTCAEv3 criteria, and dose-limiting toxicity (DLT) determination was based on the occurrence of AEs that were probably or definitely attributed to the study regimen. Efficacy was assessed using the International Myeloma Working Group (IMWG) criteria. Enrollment has completed and 16 patients remain on study. Results: Forty-four patients were enrolled, 41 are currently evaluable for safety and 32 are evaluable for efficacy. The median number of prior therapies was 2 (range 1–11), 62% of patients had prior Len exposure and 33% were Len refractory. LM doses of 75 (N = 11), 90 (N=4), and 112 (N =6) mg/m2 were evaluated in the dose-escalation phase. The most common AE was peripheral neuropathy (PN), which occurred more frequently at higher LM doses (55% at 75 mg/m2 and 100% at 90 and 112 mg/m2); Grade 3 PN was seen only in patients treated at 90 mg/m2 or above. PN emerged, in most cases, in cycles >3 and was manageable with LM dose modification. During dose escalation, 1 patient experienced Grade 4 neutropenia and hyperuricemia. The 75 mg/m2 LM dose was considered the MTD based on overall tolerability and the lower incidence of PN observed, and was further tested to determine its suitability as the RP2D in the dose expansion portion of the study (N=23 patients, 19 patients available for safety evaluation). Grade 1–2 PN occurred in 8 patients (42%) and grade 3 PN was observed only in 1 pt in the dose-expansion cohort. Two patients developed grade 3 tumor lysis syndrome (TLS). Other grade 3 AEs reported in 1 patient each (5%) in the dose-expansion cohort consisted of neutropenia, thrombocytopenia, anemia, hemolytic anemia, and LDH increase. Efficacy was observed across all dose levels and the overall response rate (ORR) was 59%, including 1 patient each with stringent complete response (sCR) and complete response (CR), 8 patients with very good partial remission (VGPR), and 9 patients with partial remission (PR). No immunogenicity against the antibody (HAHA) or DM1 component (HADA) of LM was detected. PK results from 18 patients treated at 75 mg/m2 indicate LM Cmax and exposure in this combination regimen is consistent with LM monotherapy. Conclusions: Based on all available safety data, 75 mg/m2 was considered the RP2D. LM at 75mg/m2 in combination with Len and Dex has shown objective evidence of clinical activity with an acceptable safety profile. Disclosures: Off Label Use: Lorvotusumab mertansine is not FDA approved for treatment of multiple myeloma alone or in combination with lenalidomide and dexamethasone as is investigated in this trial. Running:ImmunoGen, Inc.: Employment. Murphy:ImmunoGen, Inc.: Employment. Guild:ImmunoGen, Inc.: Employment. Carrigan:ImmunoGen, Inc: Employment. Ladd:ImmunoGen, Inc.: Employment. Wolf:ImmunoGen, Inc.: Employment, Equity Ownership. O'Leary:ImmunoGen, Inc.: Employment. Ailawadhi:Millenium Pharmaceuticals: Speakers Bureau.

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Background:Inflammatory bowel disease (IBD), which includes Crohn’s disease (CD), Ulcerative colitis (UC), and undetermined colitis may be related to psoriasis and psoriatic arthritis (PsA). Biologic therapy (BT) is useful in PsA and IBD but paradoxically has been related to IBD.Objectives:In a wide series of PsA, our aim was to assessa) the epidemiological and clinical features of associated IBD andb) its relationship with BT.Methods:All unselected consecutive patients studied in a single reference University Hospital with: a) PsA (CASPAR criteria) andb) IBD: CD, UC and undetermined colitis diagnosed by endoscopic patterns, clinical criteria and laboratory tests. A comparative study between patients with and without IBD was performedResults:We studied 306 (165 women/141 men) patients with PsA; mean age at PsA diagnosis of 41.7±15.79 years; delay of diagnosis from the onset of symptoms of 2.6±2.01 years. IBD (CD=6; UC=1 and undetermined colitis=3) was observed in 10 of 306 (3.3%, 8 women/2 men). A significant more frequency of enthesitis, positive HLA-B27 and non-significant more severe PsA (axial, and hip involvement, and a higher BASDAI, BASFI, DAPSA, PASI) was observed in patients with associated-IBD (TABLE).IBD was present before PsA in 5 patients and in the other 5, after 9.6±15.3 years of evolution of PsA. BT for PsA has been used in 1 (20%) (etanercept) of these 5 patients which developed IBD and in 67 of 296 (22.6%) without IBD (Adalimumab 45; Certolizumab 8; Infliximab 6; Golimumab 4; Etanercept 4).Conclusion:IBD in PsA was uncommon (3.3%), may be associated to a more severe PsA, and no relationship to BT was found.TABLE 1.Patients with IBD(n=10)Patients without IBD(n=296)pDEMOGRAPHIC PARAMETERSSex, n (%)2 ♂/8 ♀ (20.0/80.0)139 ♂/157 ♀ (46.9/53.1)p = 0.11Age at PsA symptoms onset (years), mean± SD39.0±15.144.2±11.4p = 0.17Age at PsA diagnosis, mean±SD41.7±15.746.4±15.8p = 0.22PsA RELATED DATAPsA type Asymmetric Oligoarticular, n (%)4.0 (40.0)159 (53.7)p = 0.59 Symmetrical Polyarthritis, n (%)0.0 (0.0)46 (15.5)p = 0.37 Axial, n (%)3.0 (30.0)40 (13.5)p = 0.31 Mixed, n (%)3.0 (30.0)51 (17.2)p = 0.54 Enthesitis, n (%)7.0 (70.0)111 (37.5)p = 0.03* Dactylitis, n (%)0.0 (0.0)79 (26.7)p = 0.70 Hip involvement n (%)4.0 (40.0)55 (18.5)p = 0.57Scores BASDAI, median [ICR]3.1 [0.0-4.4]2.2 [0.0-4.5)p = 0.64 BASFI, median [ICR]6.0[0.0–6.9]0.0 [0.0-3.3]p = 0.69 DAPSA, median [ICR]10.7 [0.0–14.62]4.3 [0.0-13.0]p = 0.31 PASI, median [ICR]2.3 [0.0–6.7]0.6 [0.0-2.38]p = 0.70Laboratory tests:HLA-B27, n (%)6.0 (60.0)23 (7.8)p = 0.001*Disclosure of Interests:Lara Sanchez-Bilbao Grant/research support from: Pfizer, David Martinez-Lopez: None declared, Natalia Palmou-Fontana: None declared, Susana Armesto: None declared, Miguel A González-Gay Grant/research support from: Pfizer, Abbvie, MSD, Speakers bureau: Pfizer, Abbvie, MSD, Ricardo Blanco Grant/research support from: AbbVie, MSD, and Roche, Speakers bureau: AbbVie, Pfizer, Roche, Bristol-Myers, Janssen, and MSD

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Colao A, De Rosa M, Sarnacchiaro F, Di Sarno A, Landi ML, Iervolino E, Zarrilli S, Merola B, Lombardi G. Chronic treatment with CV 205-502 restores the gonadal function in hyperprolactinemic males. Eur J Endocrinol 1996;135:548–52. ISSN 0804–4643 The aim of this study was to evaluate the effects of a chronic treatment with the non-ergot-derived dopamine agonist quinagolide (CV 205-502) on sexual and gonadal function in hyperprolactinemic males. Thirteen males with macroprolactinoma and one with microprolactinoma were treated with CV 205-502 at the dose of 0.15–0.6 mg/day for 6–24 months. Baseline prolactin (PRL) was 464 ± 75.7 μg/l. All the patients suffered from libido impairment, five of reduced sexual potency, six had infertility and in four bilateral induced galactorrhea was shown. The sem*n analysis revealed a severe oligoasthenospermia with reduced sperm count, motility and forward progression, with an abnormal morphology and decreased viability. A significant reduction of serum PRL levels (nadir PRL = 12.3 ± 5.4 μg/l) was obtained during the treatment. Normalization of prolactinemia was reached in 13 of the 14 patients after 3 months. After 1 year, a significant improvement of sperm parameters, in terms of increase of number (from 5600 ± 111 to 20 564 ± 587 mm3), motility at 1 h (from 24.8 ± 0.1 to 52.6 ± 0.5%), forward progression (from 24 ± 1.4 to 62.3 ± 2.9%) and normal morphology (from 53.8 ± 2.5 to 62.2 ± 2.4%), was recorded. In addition, a significant increase of serum follicle-stimulating hormone (from 5.3 ± 0.6 to 7.8 ± 0.4 U/l), luteinizing hormone (from 4.4 ± 0.5 to 7.7 ± 0.4 U/l) and testosterone (from 3.4 ± 0.4 to 4.7 ± 0.2 μg/l) was recorded. A significant increase of luteinizing hormone (9.4 ± 0.7 U/l) and testosterone (5.2 ± 0.4 μg/l), as well as a further improvement of sperm parameters, was found after 2 years of therapy. Sellar computed tomography and/or magnetic resonance showed a considerable shrinkage (⩾ 30%) of tumoral mass in 8 out of 13 patients with macroprolacinoma. Side effects were recorded in only one patient. In conclusion, the treatment with CV 205-502 normalizing PRL levels improves gonadal and sexual function and fertility in males with prolactinoma, providing good tolerability and excellent patient compliance to medical treatment. This result demonstrates that the impairment of gonadal function in hyperprolactinemic patients is a functional modification. Annamaria Colao, Department of Molecular and Clinical Endocrinology and Oncology, "Federico II" University, via S. Pansini 5, 80131 Naples, Italy

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Abstract Abstract 3125 Poster Board III-62 VTE is the most frequent complication of OS and it can be prevented through anticoagulant prophylaxis. Numerous studies have evaluated different agents for this purpose and there are new agents currently under development or recently approved for this indication. We conducted a systematic review of randomized controlled trials (RCT) evaluating administration of anticoagulants for VTE prophylaxis in OS and performed a MA of proportions to estimate the overall incidence of major VTE (proximal VTE, pulmonary embolism (PE), or death from PE), total VTE (proximal and distal VTE, PE or death from PE), symptomatic VTE and major bleeding episodes (as defined by the International Society on Thrombosis and Hemostasis). We included RCT comparing currently approved anticoagulants (head-to-head or placebo-controlled) for VTE prophylaxis in OS (hip and knee arthroplasty and hip fracture surgery) using systematic evaluation of VTE (ultrasound or venography, pulmonary angiography, CT pulmonary angiography, or ventilation perfusion scan). Heterogeneity of proportions was evaluated using a chi2 test and pooled estimates of proportions were obtained using either a fixed or a random effects model in which the weights were estimated as proposed by Laird and Mosteller. We retrieved 74 studies including180 research arms and enrolling 71,012 patients. The total number of events and evaluable patients, percentage of events and 95% CI, and number of study arms included are shown in the table. We found differences in the percentage of VTE and bleeding events associated with the use of different anticoagulants for VTE prophylaxis after OS. Due to the nature of the analysis no effect measure can be estimated. These estimates might help to design future studies. Major VTE Total VTE Symptomatic VTE Major Bleeding Cases / Evaluable Pts. (N) Percentage (95% CI) Study arms (N) Cases / Evaluable Pts. (N) Percentage (95% CI) Study arms (N) Cases / Evaluable Pts. (N) Percentage (95% CI) Study arms (N) Cases / Evaluable Pts. (N) Percentage (95% CI) Study arms (N) All patients LMWH 993/23692 5.96 (5.81, 6.11) 72 4068/22610 20.29 (20.04, 20.55) 80 193/19431 1.32 (1.27, 1.37) 35 476/28725 1.98 (1.93, 2.02) 70 UFH 234/2407 13.39 (12.86, 13.93) 14 596/2537 22.54 (22, 23.08) 17 11/339 3.24 (3.06, 3.43) 4 70/2849 2.75 (2.61, 2.89) 16 Warfarin 269/5677 6.28 (6.09, 6.46) 12 1317/4203 31.05 (30.44, 31.66) 12 71/4146 1.95 (1.83, 2.08) 6 96/6751 1.78 (1.69, 1.87) 12 Fonda 96/3673 3.81 (3.53, 4.09) 7 223/3477 6.82 (6.57, 7.07) 6 69/6398 1.06 (1.01, 1.1) 8 121/6576 1.63 (1.55, 1.71) 9 Riva 50/5025 2.02 (1.86, 2.19) 8 242/4595 13.05 (12.16, 13.94) 8 29/6252 0.46 (0.45, 0.48) 6 31/6643 0.63 (0.59, 0.68) 8 Dabi 149/4091 3.64 (3.59, 3.69) 6 834/4051 22.96 (21.91, 24.01) 6 26/3664 0.71 (0.67, 0.75) 4 67/5419 1.21 (1.17, 1.26) 6 Placebo 193/710 24.26 (23.17, 25.34) 10 379/816 49.35 (48.08, 50.62) 11 19/198 12.02 (10.32, 13.72) 3 12/753 1.59 (1.5, 1.68) 7 Total 1984/45275 129 7659/42289 140 418/40428 66 873/57716 128 Total Hip Arthroplasty LMWH 653/15978 6 (5.85, 6.16) 50 1817/14480 15.58 (15.35, 15.82) 55 81/11552 0.7 (0.69, 0.72) 19 306/18010 1.97 (1.92, 2.02) 45 UFH 187/1739 14.3 (13.64, 14.96) 11 354/1836 20.13 (19.46, 20.8) 13 11/246 4.47 (4.21, 4.73) 3 52/1451 3.2 (3.01, 3.39) 11 Warfarin 77/2758 4.28 (4.08, 4.48) 6 265/1273 20.82 (20.59, 21.04) 6 32/1833 1.75 (1.69, 1.81) 2 47/2856 2.23 (2.09, 2.37) 5 Fonda 28/1799 2.96 (2.58, 3.33) 3 85/1695 5.01 (4.91, 5.12) 2 15/2255 0.67 (0.63, 0.7) 2 69/2349 2.94 (2.87, 3.01) 3 Riva 25/2938 2.21 (1.95, 2.46) 5 73/2749 9.72 (8.92, 10.53) 5 10/3468 0.29 (0.27, 0.31) 3 14/3795 0.49 (0.44, 0.54) 5 Dabi 72/1803 3.99 (3.88, 4.11) 2 124/1766 7.02 (6.77, 7.27) 2 21/2293 0.92 (0.91, 0.93) 2 38/2309 1.65 (1.58, 1.72) 2 Placebo 105/414 26.01 (24.76, 27.27) 7 174/418 45.43 (43.74, 47.13) 7 4/147 2.72 (2.46, 2.98) 2 3/388 0.77 (0.69, 0.86) 5 Total 1147/27429 84 2892/24217 90 174/21794 33 529/31158 76 Total Knee Arthroplasty LMWH 277/6916 4.45 (4.34, 4.55) 25 2062/7326 30.72 (30.37, 31.07) 32 83/4902 1.69 (1.66, 1.73) 11 89/7808 1.14 (1.12, 1.16) 26 UFH 42/638 6.58 (6.39, 6.78) 3 226/638 35.42 (35.05, 35.79) 3 0/93 NE 1 3/318 0.94 (0.84, 1.05) 2 Warfarin 192/2919 8.1 (7.88, 8.32) 9 1052/2930 39.36 (38.69, 40.02) 9 39/2056 1.9 (1.84, 1.96) 3 28/3407 0.82 (0.79, 0.85) 8 Fonda 23/452 9.3 (7.93, 10.67) 2 45/361 12.47 (12.12, 12.81) 1 3/517 0.58 (0.51, 0.65) 1 12/601 2 (1.88, 2.11) 2 Riva 25/2087 1.2 (1.15, 1.24) 3 169/1846 18.55 (16.47, 20.63) 3 19/2784 0.68 (0.65, 0.71) 3 17/2848 0.6 (0.57, 0.63) 3 Dabi 77/2288 3.37 (3.32, 3.41) 4 710/2285 30.98 (30.42, 31.55) 4 5/1371 0.36 (0.32, 0.41) 2 29/3110 0.93 (0.89, 0.98) 4 Placebo 88/296 27.12 (24.54, 29.7) 4 205/398 55.19 (53.53, 56.84) 5 15/51 29.41 (28.16, 30.66) 1 9/365 2.47 (2.31, 2.62) 4 Total 724/15596 50 4469/15784 57 164/11774 22 187/18457 49 LMWH Low molecular weight heparin, UFH unfractionated heparin, Riva Rivaroxaban, Dabi Dabigatran etexilate Disclosures Lazo-Langner: Boehringer Ingelheim: Honoraria. Rodger:Bayer: Research Funding; Leo Pharma: Research Funding; Pfizer: Research Funding; Boehringer Ingelheim: Membership on an entity's Board of Directors or advisory committees; Biomerieux: Research Funding; GTC Therapeutics: Research Funding.

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Abstract Abstract 3451 Relapse is the major cause of treatment failure and death following reduced-intensity (RI) allogeneic hematopoietic stem cell transplantation (HSCT) for non-Hodgkin's lymphoma (NHL), yet there are no reports that focus specifically on the natural history of relapse in this patient population. We assessed relapse risks and outcomes on 120 consecutive patients (median age = 52 years; range, 28–71 years) with NHL (indolent = 43; aggressive = 77) who all received a T-cell replete allograft from HLA-matched siblings following a reduced-intensity conditioning regimen (fludarabine/cyclophosphamide). All patients were assessed for disease status at 1, 3, 6, 12, 18, 24 months post-transplant, and annually thereafter or as clinically indicated. Median event-free survival (EFS) from transplant date for all 120 patients was 11.3 months (range, 0.5–105.5+ months) with a 5-year EFS = 35%. Median EFS (months) was assessed for the following pre-transplant characteristics: chemo-resistant vs. chemo-sensitive = 3.3 vs. 39.1, p = 0.0001; pre-transplant disease status - CR vs. PR vs. SD vs. PD = not reached (NR) vs. NR vs. 11.2 vs. 1.7, p <0.0001; aggressive vs. indolent histology = 6.6 vs. 15.8, p = 0.13; number of disease sites: 0–1 vs. 2 vs. 3 vs. 4+ = 4.8 vs. 7.4 vs. 18.4 vs. 7.1, p = 0.85. Median overall survival (OS) from transplant date for all 120 patients was 71.1 months (range, 0.5–120+ months). We identified 55 patients (46%) who either relapsed or progressed post-transplant. Among those who have progressed/relapsed to date, median time to progression/relapse was 3 months (range, 0.5–46 months) with 72% of progressions/relapses occurring prior to 6 months post-transplant. The overall cumulative incidence (CI) probabilities for relapse/progression, adjusted for competing non-relapse mortality, at 3, 6, 12, 24 and 36 months were 0.169, 0.329, 0.394, 0.447, and 0.460, respectively. The association of 3-year relapse CI probabilities with pre-transplant characteristics were as follows: aggressive vs. indolent histology = 0.530 vs. 0.315; chemo-resistant vs. chemo-sensitive = 0.571 vs. 0.316; disease status prior to transplant – CR vs. PR vs. SD vs. PD = 0.210 vs. 0.217 vs. 0.597 and 0.627; number of prior treatments: 1–2 vs. 3 vs. 4 vs. 5+ = 0.375 vs. 0.418 vs. 0.613 vs. 0.450; sites of disease: 0–1 vs. 2 vs. 3 vs. 4+ = 0.458 vs. 0.516 vs. 0.331 vs. 0.579. Median OS from date of progression was 8.3 months (0.5 - 94+ months) with a 5-year OS = 32%. No patient who progressed/relapsed within 3 months post-transplant has survived beyond 12 months, with one patient still alive at 6 months. Median OS (months) from date of progression was assessed for the following characteristics: progression < 3 months vs. ≥ 3 months post-transplant = 2.6 vs. NR, p <0.0001; progression < 6 months vs. ≥ 6 months post-transplant = 5.3 vs. NR, p = 0.0002; aggressive vs. indolent histology = 7.8 vs. 18.3, p = 0.53; number of disease sites: 0–1 vs. 2 vs. 3 vs. 4+ = 5.8 vs. 13.8 vs. 4.9 vs. 12.9, p = 0.75; number of prior treatments: 1–2 vs. 3 vs. 4 vs. 5+ = 8.4 vs. NR vs. 11 vs. 5.6, p = 0.27; response vs. no response to relapse/progression treatment = NR vs. 4.7, p = 0.0087 (determined by a landmark method, beginning 30 days after progression to allow time for determination of response to relapse treatment). These data demonstrate that a significant minority of NHL patients, who relapse after RI allogeneic HSCT, can achieve long-term survival, including patients with aggressive histology. These analyses, which utilized standard clinical characteristics, identified NHL patients at higher risk for relapse and poorer outcomes once relapse occurred. In particular, disease progression/relapse occurring less than 3 months post-transplant was associated with an extremely poor prognosis; novel strategies and trials are needed for such patients. These results need to be confirmed by other groups, and these analyses need to be performed in other transplant settings (e.g. unrelated donors and myeloablative conditioning). The use of these patient characteristics, alone or in combination, may ultimately lead to a method of estimating the risk for relapse and the subsequent prognosis, if relapse should occur, in NHL patients undergoing RI allogeneic HSCT. Disclosures: No relevant conflicts of interest to declare.

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Background:The Janus kinase inhibitors (JAKi) have been increasingly used for the treatment of rheumatoid arthritis (RA) in Sweden, with baricitinib representing ~80% of prescriptions. Evidence regarding the comparative effectiveness of JAKis versus biologics (bDMARDs), and in particular non- tumour-necrosis-factor inhibitor (TNFi) bDMARDs, in real-life is limited.Objectives:To compare RA patients treated with bDMARDs and JAKi in Sweden, in terms of: (1) patient characteristics at treatment start; (2) proportions of patients remaining on therapy, and response rates, at 12 months.Methods:RA patients starting treatment in 2017 and 2018 with either a TNFi, rituximab, abatacept, interleukin 6 inhibitors (IL6i) or a JAKi as different lines of treatment were identified in the Swedish Rheumatology Quality Register. One patient could contribute with more than one treatment episode.Treatment response at 12 months was measured as EULAR good response, HAQ improvement >0.2 units, DAS28 and CDAI remission, and as 0 tender and swollen joint counts (28JC). Patients were classified as non-responders if they stopped treatment before evaluation due to safety or inefficacy. Responses for patients who stopped treatment due to pregnancy or death and patients on treatment but with missing response were imputed using multiple imputation.Proportions of responders and differences in proportions between treatment groups, adjusted using inverse probability of treatment weighting, were estimated using linear regression with robust standard errors.Results:JAKi were often used after bDMARDs, and less frequently prescribed in combination with methotrexate. Measured comorbidities were less frequent among JAKi initiators than among non-TNFi biologic initiators, but RA activity was similar (Table).Table 1.Patient characteristics at treatment initiationCharacteristicMedian (IQR) or N (%)AbataceptIL6iRituximabTNFiJAKiTreatment Starts6945346923497905Age63 (53-71)59 (48-70)65 (54-73)59 (47-68)60 (51-70)Female543 (78)441 (83)519 (75)2739 (78)759 (84)RA duration (years)13 (5-21)10 (5-18)12 (6-22)9 (3-17)13 (7-22)Rheum. factor535 (79)385 (73)588 (87)2405 (70)686 (77)DAS284.8 (3.9-5.6)4.9 (4.0-5.7)4.7 (3.8-5.5)4.4 (3.4-5.3)4.7 (3.9-5.7)HAQ1.3 (0.8-1.6)1.3 (0.8-1.8)1.3 (0.8-1.8)1.0 (0.5-1.4)1.3 (0.8-1.8)Tender joints5 (2-9)6 (3-10)5 (2-9)4 (2-8)6 (2-10)Swollen joints4 (2-6)4 (2-7)4 (2-7)3 (1-6)4 (2-7)ts/bDMARD line3 (2-4)3 (2-4)2 (1-4)1 (1-2)4 (2-6)At least one prev. TNFi539 (78)442 (83)457 (66)1448 (41)770 (85)At least one prev. non-TNFi271 (39)220 (41)243 (35)441 (13)584 (65)Methotrexate co-treatment264 (50)172 (40)286 (53)1708 (62)296 (40)Glucocorticoids co-treatment247 (47)186 (43)275 (51)1126 (41)389 (53)Cancer*90 (2.8)64 (2.3)363 (7.7)410 (1.8)20 (2.2)Cardio-vascular dis.*245 (7.5)123 (4.4)322 (6.8)749 (3.4)41 (4.4)Chronic respiratory dis.*303 (9.3)140 (5.0)473 (10.0)721 (3.2)50 (5.4)Diabetes*324 (9.9)216 (7.7)456 (9.7)1479 (6.7)69 (7.5)* any diagnosis within 5 years before start Adjusted differences in proportion with each response outcomeIn a crude comparison, 65% (61%-68%) of JAKi, 62% (59%-66%) of abatacept, 58% (53%-62%) of IL6i, 80% (77%-83%) of rituximab and 68% (67%-70%) of TNFi initiators remained on treatment at 12 months after start. Also, JAKi showed lower overall responder proportions than TNFi, rituximab and IL6i.After adjustment for demographic and socio-economic factors, RA disease activity, previous use of ts/bDMARDs, co-medication with glucocorticoids and methotrexate and comorbidities at baseline, no significant differences in responder proportions between JAKi and bDMARDs remained (Figure). Furthermore, the adjusted proportions of patients on treatment were higher for JAKi and rituximab than for the other bDMARDs.Conclusion:This preliminary analysis of patients treated in clinical practice found no statistically significant difference in effectiveness between JAKi and bDMARDs.Disclosure of Interests:Andrei Barbulescu: None declared, Johan Askling Grant/research support from: Abbvie, Astra-Zeneca, BMS, Eli Lilly, MSD, Pfizer, Roche, Samsung Bioepis, Sanofi, and UCB. These entities have entered into agreements with Karolinska Institutet with JA as principal investigator, mainly in the context of safety monitoring of biologics via the ARTIS national safety monitoring system, Katerina Chatzidionysiou Speakers bureau: Eli Lilly, Abbvie and Pfizer, Consultant of: Eli Lilly, Abbvie and Pfizer, Helena Forsblad-d’Elia: None declared, Alf Kastbom Employee of: Sanofi, Ulf Lindström: None declared, Carl Turesson Speakers bureau: Abbvie, Bristol-Myers Squibb, Medac, Pfizer, Roche, Consultant of: Roche, Grant/research support from: Bristol-Myers Squibb, Thomas Frisell: None declared

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Abstract Introduction : Hereditary hemorrhagic telangiectasia (HHT) is a rare hereditary multisystem vascular disorder causing visceral arteriovenous malformations (AVMs) and mucocutaneous bleeding. Chronic gastrointestinal bleeding and epistaxis frequently produce profound iron deficiency anemia refractory to conventional treatment. Patients with HHT have elevations in vascular endothelial growth factor (VEGF), so the anti-VEGF agent bevacizumab, a recombinant, humanized monoclonal IgG1 antibody that binds to and neutralizes circulating VEGF, is a promising systemic HHT therapy. Currently, data pertaining to the efficacy of bevacizumab for the treatment of HHT is limited to case reports and retrospective studies that do not describe the effect of bevacizumab on objective hematologic parameters (Guilhem et al 2017, Iyer et al 2018). As our institution is an HHT center that has developed a pathway for the use of bevacizumab in HHT patients, we performed a retrospective analysis assessing the efficacy of bevacizumab to alleviate chronic bleeding as measured by improvement in hemoglobin concentration, need for red cell transfusions and iron infusions, and epistaxis control. Management of bleeding in HHT patients is an off-label use of bevacizumab. Methods : All HHT patients treated with systemic bevacizumab for chronic bleeding were selected for retrospective analysis. Data was collected for each patient over a 14-month course, divided into a pretreatment period (six months), induction period (two months), and maintenance period (six months) and included demographics, baseline HHT characteristics, epistaxis grade, surgical interventions, bevacizumab dosing, adverse events, hemoglobin, red cell transfusions, intravenous iron infusions, and other anemia and/or bleeding-directed therapies. Additionally, the peak hemoglobin on bevacizumab over the course of all available follow-up was collected for each patient. Our institution's bevacizumab treatment pathway began with an induction phase (5 mg/kg of IV bevacizumab every two weeks for four treatments) followed by a maintenance phase (5 mg/kg administered monthly thereafter). Statistical tests used in data analysis included the paired t-test, Wilcoxon signed rank test, and Fisher's exact test. Results : 13 HHT patients were treated with bevacizumab for chronic bleeding for a median of 13.9 (range, 4.9-30.1) months. Baseline patient characteristics are shown in Table 1 and hematologic parameters during the pretreatment, induction, and maintenance periods are shown in Table 2. Compared with pretreatment values, bevacizumab treatment increased the mean hemoglobin by 4.0 g/dL (95% CI, 2.6-5.3 g/dL) [mean (95% CI) hemoglobin 8.5 (7.8, 9.9) g/dL versus 12.5 (11.2, 13.7) g/dL, p<0.001)], reduced red cell units transfused by 92% [median of 6 (range, 0-59) units versus 0 (range, 0-15) units, p=0.004], and reduced quantity of iron infused by 73% [mean (95% CI) 462 (257, 668) mg/month versus 126 (75, 178) mg/month, p=0.002]. The peak hemoglobin value measured over the course of all available follow up ranged from 12.1-17.6 mg/dL (Figure 1), with all but two patients (85%) achieving a hemoglobin within the normal range for gender. Twelve of 13 patients did not require red cell transfusions during the entire maintenance period and 11 of 13 patients did not require iron infusions during the latter half of the maintenance period (Figure 2). Epistaxis control (reduction of epistaxis grade to <2) was achieved in 85% with bevacizumab, versus 0% before treatment (p<0.001) and all but one patient experienced improvement in epistaxis grade. No patient required nasal or GI procedures during the maintenance period. Four out of 5 patients receiving antifibrinolytic agents or erythropoiesis-stimulating agents prior to initiation of bevacizumab were able to discontinue these agents during bevacizumab induction and not resume them thereafter. Bevacizumab was well-tolerated, with two patients (15%) developing grade 3 hypertension requiring medical management. Conclusions : Systemic bevacizumab was highly effective to treat chronic bleeding and iron deficiency anemia in HHT. This study is the first to demonstrate the impact of bevacizumab on objective hematologic parameters, such as hemoglobin and iron infusion requirements. Further study is needed to confirm the benefit magnitude and define optimal dosing, treatment duration, and long-term safety. Disclosures Al-Samkari: Agios: Consultancy. Kuter:Protalex: Research Funding; Rigel: Consultancy, Research Funding; Novartis: Consultancy; Amgen Inc.: Consultancy; Argenx: Consultancy; Bioverativ: Consultancy, Research Funding; BMS: Research Funding; Syntimmune: Consultancy; Pfizer: Consultancy; Dova Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees; Principia: Research Funding; ONO: Consultancy.