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Background: BAY 1862864 is an α-particle emitting 227Th-labeled CD22-targeting antibody. This first-in-human dose-escalation phase I study evaluated BAY 1862864 in patients with CD22-positive relapsed/refractory B cell non-Hodgkin lymphoma (R/R-NHL). Materials and Methods: BAY 1862864 intravenous injections were administered at the starting 227Th radioactivity dose of 1.5 MBq (2 or 10 mg antibody), and the radioactivity dose escalated in ∼1.5 MBq increments (10 mg antibody) until the maximum tolerated dose (MTD) was reported. The primary objective was to determine the safety, tolerability, and MTD. Results: Twenty-one patients received BAY 1862864. Two dose-limiting toxicities (grade 3 febrile neutropenia and grade 4 thrombocytopenia) were reported in one patient in the 4.6 MBq (10 mg antibody) cohort. The MTD was not reached. Ten (48%) patients reported grade ≥3 treatment-emergent adverse events, with the most common being neutropenia, thrombocytopenia, and leukopenia, each occurring in 3 (14%) patients. Pharmacokinetics demonstrated the dose proportionality and stability of BAY 1862864 in the blood. The objective response rate (ORR) was 25% (5/21 patients) according to the LUGANO 2014 criteria, including 1 complete and 4 partial responses. The ORR was 11% (1/9) and 30% (3/10) in patients with relapsed high- and low-grade lymphomas, respectively. Conclusions: BAY 1862864 was safe and tolerated in patients with R/R-NHL. Clinical Trial Registration numbers: NCT02581878 and EudraCT 2014-004140-36. [ABSTRACT FROM AUTHOR]

Laparoscopic techniques are gradually replacing many common surgical procedures that are performed in an increasingly aging population. Laparoscopy places different physiologic demands on the body than in open surgery. PubMed was searched for evidence related to the use of laparoscopy in the elderly population to treat common surgical pathologies. Randomized trials, systematic reviews, and metaanalyses were preferred. Currently, over 40% of all surgeries performed in the U.S. are on patients older than 65 years. By the end of the 21st century, Americans are expected to live 20 years longer than the current average. However, elderly patients clearly show higher rates of surgical morbidity and mortality overall. Laparoscopic techniques show decreased wound complications, post-operative ileus, intraoperative blood loss, and reduced need for post-operative rehabilitation. In conclusion, laparoscopic surgery is safe in the elderly population and affords multiple advantages including decreased pain and convalescence. However, the physiology of laparoscopy places demands on elderly patients that typically present with more medical comorbidities. [ABSTRACT FROM AUTHOR]

Introduction: Smoking and postoperative complications are well documented across surgical specialties. Preoperative smoking cessation is frequently recommended by surgeons. In this study, we assessed to what degree documented smoking history increased a patient's risk of postoperative complications. Methods: The Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program (MBSAQIP) database for the years 2015-2018 was used. Patients were included if they underwent primary sleeve gastrectomy (SG) or Rouxen-Y gastric bypass (LRYGB). Patients with a documented smoking history were assigned to the "SH" cohort and patients without smoking history were assigned to the "NSH" cohort. Patients without documentation regarding smoking history, missing variables, younger than 18, with prior surgery, or lost to follow-up were excluded. 30-day morbidity and mortality data were assessed. Multiple logistic regression analysis was made based on all available patient characteristics and perioperative factors, continuous variables were analyzed using Student's t-test and categorical variables were compared using the chi-square test. Results: After evaluation of 760,076 patients on the MBSAQIP database, 650,930 patients underwent non-revisional bariatric surgery, including 466,270 SG and 184,660 LRYGB. Of the total patients included in the study, 44,606 patients were assigned to the SH cohort and 479,601 were assigned to the NSH cohort. 4628 of patients did not have documented smoking status. Within 30 days SH patients had higher rates of readmission (4.2% vs 3.7%, P < .0001), reoperation (1.3% vs 1.1%, P < .0001), unplanned intubation (.2% vs .1%, P = .0212), and unplanned ICU admission (.7% vs .0.6%, P = .0022). Conclusion: SH patients undergoing bariatric surgery were at significantly increased risk of readmission and reoperation within 30 days of procedure. In addition, SH patients were more likely to have unplanned intubation and unplanned ICU admission. Given the higher rates of complications in smoking patients, this study would suggest that preoperative smoking cessation in patients prior to primary bariatric surgery might be beneficial. Further study is warranted to compare short-term cessation vs long-term cessation preoperatively, which was not assessed in our study. [ABSTRACT FROM AUTHOR]

Background: Studies examining utilization and impact of venous thromboembolism (VTE) chemoprophylaxis for patients undergoing bariatric surgery are limited. Determination of the optimal prophylactic regimen to minimize complications is crucial.Methods: The Cerner Health Facts database from 2003 to 2013 was queried using ICD-9 codes to identify patients undergoing laparoscopic sleeve gastrectomy (LSG) and Roux-en-Y gastric bypass (RYGB). VTE chemoprophylaxis regimens were divided into pre-operative alone (PreP), post-operative alone (PostP), both pre-operative and post-operative (PPP), or no prophylaxis (NP). Specific chemoprophylaxis agents were compared. Comparisons in inpatient clinical outcomes were based on univariate analysis and multivariable logistic regression when appropriate.Results: We identified 11,860 patients who underwent LSG and RYGB. 634 (5.35%) had PreP, 4593 (38.73%) had PostP, 2646 (22.31%) had PPP, and 3987 (33.62%) had NP. The overall rates of transfusion, DVT, and PE were 2.48, 0.27, and 0.18%, respectively. Patients without chemoprophylaxis had higher rate of DVT compared to any chemoprophylaxis (0.58 vs 0.11%, p < 0.0001), without any significant difference in PE rate. Patients with pre-operative chemoprophylaxis were more likely to receive transfusion compared to patients with post-operative prophylaxis alone (OR 1.98, 95% CI 1.28-3), without significant difference in having VTE. When examining heparin versus enoxaparin versus mixed regimen in the PostP group, mixed regimen was associated with increased transfusion requirements (p < 0.001).Conclusions: Bariatric surgical VTE chemoprophylaxis utilization is inconsistent. In this study, post-operative VTE chemoprophylaxis was associated with decreased VTE events compared to NP, while minimizing bleeding compared to PreP. Mixed therapy using heparin and enoxaparin was associated with more bleeding. [ABSTRACT FROM AUTHOR]

Introduction: Current guidelines support laparoscopic cholecystectomy as the treatment of choice for pregnant women with symptomatic gallbladder disease, regardless of the trimester. Early intervention has remained the standard of care, but recent evidence has challenged this practice in pregnant women. We sought to compare surgical and maternal–fetal outcomes of antepartum versus postpartum cholecystectomy in New York State. Methods: Between 2005 and 2014, the New York Statewide Planning and Research Cooperative System (SPARCS) database was queried for patients who underwent cholecystectomy within 3 months before (antepartum cholecystectomy, APCCY: n = 82) and after (postpartum cholecystectomy, PPCCY: n = 5040) childbirth to approximate third-trimester operations. All patients who underwent cholecystectomy during pregnancy (n = 971) were extracted to evaluate inter-trimester differences. Subgroup analysis compared APCCY patients who were not hospitalized within 1 year before APCCY (n = 80) and PPCCY patients who were hospitalized within 1 year before childbirth (n = 29) for symptomatic biliary disease. Multivariable generalized linear regression models were used to characterize the association between timing of cholecystectomy and several primary outcomes: length of stay (LOS), 30-day non-pregnancy, non-delivery readmission (NPND), bile duct injury (BDI), composite maternal outcome (antepartum hemorrhage, preterm delivery, cesarean section), any complications, and fetal demise. Results: Third-trimester APCCY women had longer LOS (Ratio: 1.44, 95% CI [1.26–1.66], p < 0.0001) and greater incidence of preterm delivery (OR 2.54, 95% CI [1.37–4.43], p = 0.0019). Cholecystectomy timing was not independently associated with differences in composite maternal outcome (p = 0.1480), BDI (p = 0.2578), 30-day NPND readmission (p = 0.7579), any complications (p = 0.2506), and fetal demise (2.44% versus 0.44%, p = 0.0545). Subgroup analysis revealed no differences in any of the seven outcomes. Conclusions: New York Statewide data suggest that although laparoscopic cholecystectomy is safe in pregnancy, delay of cholecystectomy should be discussed in the third trimester due to an increased risk for preterm delivery. [ABSTRACT FROM AUTHOR]

Introduction: The purpose of this study was to evaluate the rate of cholecystectomy before and after adoption of an emergency general surgery (EGS) model at our institution.Methods: A longitudinal, observational study was conducted prior to and following introduction of an EGS model at our institution. Using the New York SPARCS Administrative Database, all adult patients presenting to the emergency department with gallbladder-related emergencies were identified. The rates of laparoscopic and open cholecystectomies performed 3 years prior and 3 years following the adoption of the EGS model were examined. A multivariable logistic regression model was used to compare the incidence of cholecystectomy at initial ED visit at our institution pre- and post-EGS introduction as well as to those in the rest of the state as an external control group, while adjusting for potentially confounding factors.Results: There were 176,159 total ED visits of patients with gallbladder emergencies (154,743 excluding repeat presenters) in the studied period in NY State. Of these, 63,912 patients (41.3%) had a concurrent cholecystectomy in NY State. The rate of cholecystectomy at these institutions remained relatively steady from 38.8% from 2010 to 2013 and 38.6% from 2013 to 2016. At our institution, there were 2039 gallbladder emergencies, and of those 755 underwent cholecystectomy. At our institution, there was an increase from 28.21% 3 years prior to the adoption of the EGS model to 40.2% in the following 3 years (RR = 1.06, 95% CI 1.0164-1.1078, p = 0.0069).Conclusion: The initiation of the EGS model at a tertiary center was associated with a significant increase in the number of concurrent cholecystectomies from 28.21 to 40.2% over a 6-year period. This change was accompanied by an increase in the number of patient comorbidities and a lower insurance status. [ABSTRACT FROM AUTHOR]

Purpose: The IDEAL-CRT phase 1/2 multicenter trial of isotoxically dose-escalated concurrent chemoradiation for stage II/III non-small cell lung cancer investigated two 30-fraction schedules of 5 and 6 weeks' duration. We report toxicity, tumor response, progression-free survival (PFS), and overall survival (OS) for both schedules, with long-term follow-up for the 6-week schedule.Methods and Materials: Patients received isotoxically individualized tumor radiation doses of 63 to 71 Gy in 5 weeks or 63 to 73 Gy in 6 weeks, delivered concurrently with 2 cycles of cisplatin and vinorelbine. Eligibility criteria were the same for both schedules.Results: One-hundred twenty patients (6% stage IIB, 68% IIIA, 26% IIIB, 1% IV) were recruited from 9 UK centers, 118 starting treatment. Median prescribed doses were 64.5 and 67.6 Gy for the 36 and 82 patients treated using the 5- and 6-week schedules. Grade ≥3 pneumonitis and early esophagitis rates were 3.4% and 5.9% overall and similar for each schedule individually. Late grade 2 esophageal toxicity occurred in 11.1% and 17.1% of 5- and 6-week patients. Grade ≥4 adverse events occurred in 17 (20.7%) 6-week patients but no 5-week patients. Four adverse events were grade 5, with 2 considered radiation therapy related. After median follow-up of 51.8 and 26.4 months for the 6- and 5-week schedules, median OS was 41.2 and 22.1 months, respectively, and median PFS was 21.1 and 8.0 months. In exploratory analyses, OS was significantly associated with schedule (hazard ratio [HR], 0.56; 95% confidence interval [CI], 0.32-0.98; P = .04) and fractional clinical/internal target volume receiving ≥95% of the prescribed dose (HR, 0.88; 95% CI, 0.77-1.00; P = .05). PFS was also significantly associated with schedule (HR, 0.53; 95% CI, 0.33-0.86; P = .01).Conclusions: Toxicity in IDEAL-CRT was acceptable. Survival was promising for 6-week patients and significantly longer than for 5-week patients. Survival might be further lengthened by following the 6-week schedule with an immune agent, motivating further study of such combined optimized treatments. [ABSTRACT FROM AUTHOR]

Background: Marginal ulcerations (MU) are a common and concerning complication following Roux-en-Y gastric bypass (RYGB) surgery. The aim of the present study was to examine the progression of MU and identify risk factors for the need for surgical intervention in patients with MU following RYGB.Methods: A New York state longitudinal administrative database was queried to identify patients who underwent RYGB between 2005 and 2010 and who were followed for at least 4 years for the development of MU using ICD-9 and CPT codes. Patients with perforation as their first presentation of MU were excluded. Multivariable Cox proportional hazard model was built to identify risk factors for surgical intervention. Hazard ratios (HR) with 95% confidence intervals (CI) were reported.Results: We identified 35,075 patients who underwent RYGB. Mean age was 42.47 ± 10.90 years and most were female (81.08%). There were 2201 (6.28%) patients with MU, of which 204 (9.27% of MU; 0.58% of RYGB overall) required surgery. The estimated cumulative incidence of having surgical intervention 1, 2, 5, and 8 years after MU diagnosis was 6% (95% CI 5-7%), 8% (95% CI 7-9%), 13% (95% CI 11-14%), and 17% (95% CI 13-20%), respectively. At time of MU diagnosis, younger age (HR 0.93 every 5 years, 95% CI 0.87-0.99), white race (HR 1.60, 95% CI 1.15-2.23), and weight loss (HR 2.82, 95% CI 1.62-4.88) were independent risk factors for subsequent surgical intervention for MU. Estimated cumulative incidence of MU recurrence was 15% (95% CI 9-22%) and 24% (95 CI% 15-32%) at 6 and 12 months after surgical intervention.Conclusions: The need for surgical intervention for MU after RYGB is uncommon. Young age, white race, and marked weight loss are risk factors for surgical intervention. Such patients may benefit from early intensive medical therapy at the time of MU diagnosis. [ABSTRACT FROM AUTHOR]

Background: Roux-en-Y-gastric bypass (RYGB) and sleeve gastrectomy (SG) are commonly performed bariatric procedures that are associated with a significant learning curve. The effect of surgeon experience on perioperative outcomes and safety is established, but the effect of trainee participation remains unclear. The purpose of this study was to assess the impact of trainees on early perioperative safety of bariatric surgery.Methods: Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program database for 2015 was used to identify non-revisional laparoscopic and robotic RYGB and SG procedures. Comparisons were made based on assistant level. Multivariable logistic and linear regression methodology was used to compare clinical outcomes.Results: There were 35,354 laparoscopic RYGB, 2896 robotic RYGB, 79,717 laparoscopic SG, and 5449 robotic SG procedures examined. 21,257 (17%) and 11,322 (9%) of all procedures were performed with a resident or fellow, respectively. Fellow presence was independently associated with the development of complications for all procedure types except robotic SG when compared to non-trainee [odds ratio (OR) 1.31, 2.20, 1.28 for laparoscopic RYGB, robotic RYGB, and laparoscopic SG, respectively]. The most common events were urinary tract and superficial surgical site infections. This negative impact of fellow on overall complications was eliminated after accounting for operative duration. In laparoscopic SG, resident participation was associated with higher leak rate (OR 1.61), readmission (OR 1.18), re-intervention (OR 1.4), and complication rate (OR 1.32) compared to non-trainee, even after accounting for procedural duration. In robotic SG, there was no impact of trainee on outcomes.Conclusions: Although fellow training is associated with higher overall complication rate, there is no such impact on major safety benchmarks, including leak rate and re-operation. In contrast, the impact of resident trainees on SG outcomes is substantial. Operative involvement of trainees in bariatric surgery leads to different outcomes based on trainee level and should be judiciously considered during the programmatic design of bariatric educational curricula. [ABSTRACT FROM AUTHOR]

Background: To quantify the impact of body mass index (BMI) on surgical site infection (SSI) following abdominal wall reconstruction (AWR) using component separation techniques and attempt to identify obesity-related targets, such as BMI, that can be potentially used to guide preoperative patient optimization. Though AWR has established perioperative outcomes for hernia repair, the applicability in the obese population is not well established.Methods: The 2005-2013 ACS-NSQIP participant use file was reviewed to compare SSI, severe, and overall morbidity in non-emergent AWR patients based on BMI. Multivariable logistic regression was used to control for patient demographics and comorbidities. Odds ratios (OR) with 95% confidence intervals were reported.Results: We identified 4488 patients. The average BMI was 32.76 ± 7.70 kg/m2. The majority of cases (76.8%) had wound classified as clean. The SSI rate significantly increased at a BMI of ≥ 35 kg/m2 compared to < 35 (18.5% vs. 10.5%, p < 0.0001). There was no significant different in SSI rate between BMI 35-40 and > 40. After controlling for differences in baseline characteristics and wound classification, BMI ≥ 35 kg/m2 was independently associated with SSI (OR 1.47, 1.21-1.78), minor complications (OR 1.65, 1.41-1.94), major complications (OR 1.91, 1.60-2.27), re-operation (OR 1.59, 1.23-2.05), and hospital re-admission (OR 1.93, 1.23-3.02).Conclusion: There is a significant increase in SSI and other perioperative complications in patients with a BMI ≥ 35 kg/m2 undergoing AWR. Higher BMI is also independently associated with higher resource utilization in this patient population. Severely obese patients in need of AWR may benefit from a structured preoperative weight loss intervention. [ABSTRACT FROM AUTHOR]

Background: Since the introduction of laparoscopic cholecystectomy (LC), there has been continued evolution in technique, instrumentation and postoperative management. With increased experience, LC has migrated to the outpatient setting. We asked whether increased availability and experience has impacted incidence of and indications for LC.Methods: The New York (NY) State Planning and Research Cooperative System longitudinal administrative database was utilized to identify patients who underwent cholecystectomy between 1995 and 2013. ICD-9 and CPT procedure codes were extracted corresponding to laparoscopic and open cholecystectomy and the associated primary diagnostic codes. Data were analyzed as relative change in incidence (normalized to 1000 LC patients) for respective diagnoses.Results: From 1995 to 2013, 711,406 cholecystectomies were performed in NY State: 637,308 (89.58 %) laparoscopic. The overall frequency of cholecystectomy did not increase (1.23 % increase with a commensurate population increase of 6.32 %). Indications for LC during this time were: 72.81 % for calculous cholecystitis (n = 464,032), 4.88 % for biliary colic (n = 31,124), 8.98 % for acalculous cholecystitis (n = 57,205), 3.01 % for gallstone pancreatitis (n = 19,193), and 1.59 % for biliary dyskinesia (n = 10,110). The incidence of calculous cholecystitis declined (-20.09 %, p < 0.0001) between 1995 and 2013; meanwhile, other diagnoses increased in incidence: biliary colic (+54.96 %, p = 0.0013), acalculous cholecystitis (+94.24 %, p < 0.0001), gallstone pancreatitis (+107.48 %, p < 0.0001), and biliary dyskinesia (+331.74 %, p < 0.0001). Outpatient LC incidence catapulted to 48.59 % in 2013, from 0.15 % in 1995, increasing >320-fold. Analysis of LC through 2014 revealed increasing rates of digestive, infectious, respiratory, and renal complications, with overall cholecystectomy complication rates of 9.29 %.Conclusion: A shifting distribution of operative indications and increasing rates of complications should prompt careful consideration prior to surgery for benign biliary disease. For what is a common procedure, LC carries substantial risk of complications, thus requiring the patient to be an active participant and to share in the decision-making process. [ABSTRACT FROM AUTHOR]

Purpose: To report toxicity and early survival data for IDEAL-CRT, a trial of dose-escalated concurrent chemoradiotherapy (CRT) for non-small cell lung cancer.Patients and Methods: Patients received tumor doses of 63 to 73 Gy in 30 once-daily fractions over 6 weeks with 2 concurrent cycles of cisplatin and vinorelbine. They were assigned to 1 of 2 groups according to esophageal dose. In group 1, tumor doses were determined by an experimental constraint on maximum esophageal dose, which was escalated following a 6 + 6 design from 65 Gy through 68 Gy to 71 Gy, allowing an esophageal maximum tolerated dose to be determined from early and late toxicities. Tumor doses for group 2 patients were determined by other tissue constraints, often lung. Overall survival, progression-free survival, tumor response, and toxicity were evaluated for both groups combined.Results: Eight centers recruited 84 patients: 13, 12, and 10, respectively, in the 65-Gy, 68-Gy, and 71-Gy cohorts of group 1; and 49 in group 2. The mean prescribed tumor dose was 67.7 Gy. Five grade 3 esophagitis and 3 grade 3 pneumonitis events were observed across both groups. After 1 fatal esophageal perforation in the 71-Gy cohort, 68 Gy was declared the esophageal maximum tolerated dose. With a median follow-up of 35 months, median overall survival was 36.9 months, and overall survival and progression-free survival were 87.8% and 72.0%, respectively, at 1 year and 68.0% and 48.5% at 2 years.Conclusions: IDEAL-CRT achieved significant treatment intensification with acceptable toxicity and promising survival. The isotoxic design allowed the esophageal maximum tolerated dose to be identified from relatively few patients. [ABSTRACT FROM AUTHOR]