Background and Aims Symptomatic pancreatic walled-off necrosis (WON) may be managed by endoscopic transmural drainage and endoscopic transmural necrosectomy, with stent placement at endoscopic ...drainage sites. The optimal stent choice is yet to be determined. We compared outcomes after endoscopic management of WON using either large-caliber fully covered self-expandable metal stents (LC-SEMSs) or double-pigtail plastic stents (DPPSs). Methods We performed a retrospective comparison of outcomes among patients who received LC-SEMSs or DPPSs before endoscopic transmural necrosectomy for WON. Results Among 94 patients included, WON resolution rates did not differ between the DPPS (36 patients) and LC-SEMS (58 patients) groups, whether concomitant percutaneous drainage was considered a failure (75% vs 82.8%; P = .36) or not (91.7% vs 94.8%; P = .55). Of 75 patients (80%) successfully treated without percutaneous drainage, 37 (49%) underwent endoscopic transmural drainage without subsequent endoscopic transmural necrosectomy. WON was more likely to resolve without subsequent endoscopic transmural necrosectomy in the LC-SEMS group than the DPPS group (60.4% vs 30.8%; P = .01). WON resolution without subsequent endoscopic transmural necrosectomy remained more likely with LC-SEMSs (odds ratio, 4.5 95% confidence interval, 1.5-15.5) after adjusting for patient age and size and location of WON. Rates of adverse events were similar except for clinically significant bleeding requiring endoscopic intervention, which was higher with DPPSs than LC-SEMSs (14% vs 2%; P = .02). Conclusion Management of pancreatic WON with LC-SEMSs appears to decrease both the need for repeated necrosectomy procedures and the risk of intervention-related hemorrhage.
Summary Background Treatments for small-cell lung cancer (SCLC) after failure of platinum-based chemotherapy are limited. We assessed safety and activity of nivolumab and nivolumab plus ipilimumab in ...patients with SCLC who progressed after one or more previous regimens. Methods The SCLC cohort of this phase 1/2 multicentre, multi-arm, open-label trial was conducted at 23 sites (academic centres and hospitals) in six countries. Eligible patients were 18 years of age or older, had limited-stage or extensive-stage SCLC, and had disease progression after at least one previous platinum-containing regimen. Patients received nivolumab (3 mg/kg bodyweight intravenously) every 2 weeks (given until disease progression or unacceptable toxicity), or nivolumab plus ipilimumab (1 mg/kg plus 1 mg/kg, 1 mg/kg plus 3 mg/kg, or 3 mg/kg plus 1 mg/kg, intravenously) every 3 weeks for four cycles, followed by nivolumab 3 mg/kg every 2 weeks. Patients were either assigned to nivolumab monotherapy or assessed in a dose-escalating safety phase for the nivolumab/ipilimumab combination beginning at nivolumab 1 mg/kg plus ipilimumab 1 mg/kg. Depending on tolerability, patients were then assigned to nivolumab 1 mg/kg plus ipilimumab 3 mg/kg or nivolumab 3 mg/kg plus ipilimumab 1 mg/kg. The primary endpoint was objective response by investigator assessment. All analyses included patients who were enrolled at least 90 days before database lock. This trial is ongoing; here, we report an interim analysis of the SCLC cohort. This study is registered with ClinicalTrials.gov , number NCT01928394. Findings Between Nov 18, 2013, and July 28, 2015, 216 patients were enrolled and treated (98 with nivolumab 3 mg/kg, three with nivolumab 1 mg/kg plus ipilimumab 1 mg/kg, 61 with nivolumab 1 mg/kg plus ipilimumab 3 mg/kg, and 54 with nivolumab 3 mg/kg plus ipilimumab 1 mg/kg). At database lock on Nov 6, 2015, median follow-up for patients continuing in the study (including those who had died or discontinued treatment) was 198·5 days (IQR 163·0–464·0) for nivolumab 3 mg/kg, 302 days (IQR not calculable) for nivolumab 1 mg/kg plus ipilimumab 1 mg/kg, 361·0 days (273·0–470·0) for nivolumab 1 mg/kg plus ipilimumab 3 mg/kg, and 260·5 days (248·0–288·0) for nivolumab 3 mg/kg plus ipilimumab 1 mg/kg. An objective response was achieved in ten (10%) of 98 patients receiving nivolumab 3 mg/kg, one (33%) of three patients receiving nivolumab 1 mg/kg plus ipilimumab 1 mg/kg, 14 (23%) of 61 receiving nivolumab 1 mg/kg plus ipilimumab 3 mg/kg, and ten (19%) of 54 receiving nivolumab 3 mg/kg plus ipilimumab 1 mg/kg. Grade 3 or 4 treatment-related adverse events occurred in 13 (13%) patients in the nivolumab 3 mg/kg cohort, 18 (30%) in the nivolumab 1 mg/kg plus ipilimumab 3 mg/kg cohort, and ten (19%) in the nivolumab 3 mg/kg plus ipilimumab 1 mg/kg cohort; the most commonly reported grade 3 or 4 treatment-related adverse events were increased lipase (none vs 5 8% vs none) and diarrhoea (none vs 3 5% vs 1 2%). No patients in the nivolumab 1 mg/kg plus ipilimumab 1 mg/kg cohort had a grade 3 or 4 treatment-related adverse event. Six (6%) patients in the nivolumab 3 mg/kg group, seven (11%) in the nivolumab 1 mg/kg plus ipilimumab 3 mg/kg group, and four (7%) in the nivolumab 3 mg/kg plus ipilimumab 1 mg/kg group discontinued treatment due to treatment-related adverse events. Two patients who received nivolumab 1 mg/kg plus ipilimumab 3 mg/kg died from treatment-related adverse events (myasthenia gravis and worsening of renal failure), and one patient who received nivolumab 3 mg/kg plus ipilimumab 1 mg/kg died from treatment-related pneumonitis. Interpretation Nivolumab monotherapy and nivolumab plus ipilimumab showed antitumour activity with durable responses and manageable safety profiles in previously treated patients with SCLC. These data suggest a potential new treatment approach for a population of patients with limited treatment options and support the evaluation of nivolumab and nivolumab plus ipilimumab in phase 3 randomised controlled trials in SCLC. Funding Bristol-Myers Squibb.
Summary Background Comprehensive long-term data on atrial fibrillation trends in men and women are scant. We aimed to provide such data through analysis of the Framingham cohort over 50 years. ...Methods We investigated trends in incidence, prevalence, and risk factors for atrial fibrillation and its association with stroke and mortality after onset in 9511 participants enrolled in the Framingham Heart Study between 1958 and 2007. We analysed trends within 10 year groups (1958–67, 1968–77, 1978–87, 1988–97, and 1998–2007), stratified by sex. Findings During 50 years of observation (202 417 person-years), 1544 cases of new-onset atrial fibrillation occurred (of whom 723 47% were women). Between 1958–67 and 1998–2007, age-adjusted prevalence of atrial fibrillation quadrupled from 20·4 to 96·2 cases per 1000 person-years in men and from 13·7 to 49·4 cases per 1000 person-years in women; age-adjusted incidence increased from 3·7 to 13·4 new cases per 1000 person-years in men and from 2·5 to 8·6 new cases per 1000 person-years in women (ptrend <0·0001 for all comparisons). For atrial fibrillation diagnosed by electrocardiograph (ECG) during routine Framingham examinations, age-adjusted prevalence per 1000 person-years increased (12·6 in 1958–67 to 25·7 in 1998–2007 in men, ptrend =0·0007; 8·1 to 11·8 in women, ptrend =0·009). However, age-adjusted incidence of atrial fibrillation by Framingham Heart Study ECGs did not change significantly with time. Although the prevalence of most risk factors changed over time, their associated hazards for atrial fibrillation changed little. Multivariable-adjusted proportional hazards models revealed a 74% (95% CI 50–86%) decrease in stroke (hazards ratio HR 3·77, 95% CI 1·98–7·20 in 1958–1967 compared with 1998–2007; ptrend =0·0001) and a 25% (95% CI −3–46%) decrease in mortality (HR 1·34, 95% CI 0·97–1·86 in 1958–1967 compared with 1998–2007; ptrend =0·003) in 20 years following atrial fibrillation onset. Interpretation Trends of increased incidence and prevalence of atrial fibrillation in the community were probably partly due to enhanced surveillance. Measures are needed to enhance early detection of atrial fibrillation, through increased awareness coupled with targeted screening programmes and risk factor-specific prevention. Funding NIH, NHLBI, NINDS, Deutsche Forschungsgemeinschaft.
Total joint arthroplasty is the most frequently performed orthopaedic procedure in the United States. The purpose of the present study was to identify differences in thirty-day morbidity and ...mortality following primary total hip and total knee arthroplasty according to smoking status and pack-year history of smoking.
We queried the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) database to identify patients who had undergone primary total hip or total knee arthroplasty between 2006 and 2012. Patients were stratified by smoking status and pack-year history of smoking. Thirty-day rates of mortality, wound complications, and total complications were compared with use of univariate and multivariate analyses.
We identified 78,191 patients who had undergone primary total hip or total knee arthroplasty. Of these, 81.8% (63,971) were nonsmokers, 7.9% (6158) were former smokers, and 10.3% (8062) were current smokers. Current smokers had a higher rate of wound complications (1.8%) compared with former smokers and nonsmokers (1.3% and 1.1%, respectively; p < 0.001). Former smokers had a higher rate of total complications (6.9%) compared with current smokers and nonsmokers (5.9% and 5.4%, respectively; p < 0.001). Multivariate analysis identified current smokers as being at increased risk of wound complications (odds ratio OR, 1.47; 95% confidence interval CI, 1.21 to 1.78), particularly deep wound infection, while both current smokers (OR, 1.18; 95% CI, 1.06 to 1.31) and former smokers (OR, 1.20; 95% CI, 1.08 to 1.34) were at increased total complication risk. Increasing pack-year history of smoking resulted in increasing total complication risk.
On the basis of our findings, current smokers have an increased risk of wound complications and both current and former smokers have an increased total complication risk following total hip or total knee arthroplasty.
Abstract Recently, the government has moved towards public reporting of 30-day readmission rates after elective primary total knee (TKA) and total hip arthroplasty (THA). We identified 11,814 and ...8105 patients who underwent primary TKA and THA from the 2011 ACS NSQIP. Overall readmission rates within 30-days of surgery were 4.6% for TKA and 4.2% for THA. Complications associated with readmission were predominantly wound infections, sepsis, thromboembolic, cardiac, and respiratory related. In TKA, multivariate analysis identified age ( P = 0.002), male gender ( P = 0.03), cancer history ( P = 0.008), elevated BUN ( P = 0.002), a bleeding disorder ( P < 0.001) and high ASA class ( P < 0.001) as predictors of readmission. In THA, obesity ( P = 0.008), steroid use ( P = 0.037), a bleeding disorder ( P = 0.002), dependent functional status ( P = 0.022), and high ASA class ( P < 0.001) predicted readmission. Understanding characteristics associated with readmission will be essential for equitable patient risk stratification.
Abstract Background Increased operative time has been associated with increased complications following TJA. The purpose of the present study was to investigate the effect of operative time on ...short-term complications following TJA while also identifying patient and operative factors associated with prolonged operative times. Methods The American College of Surgeons (ACS) National Surgical Quality Improvement Program (NSQIP) database was queried from 2011-2013 to identify all patients who underwent primary total hip or knee arthroplasty. Patients were stratified by operative time, and 30-day morbidity and mortality data compared using univariate and multivariable analyses. Results We identified 99,444 patients who underwent primary TJA. The overall incidence of complications following TJA was 4.9%. Overall complications were increased in patients with operative times >120 minutes (5.9%) as compared to patients with operative times <60 minutes or 60-120 minutes (4.6% and 4.8%, respectively; p<0.001). Wound complications, including surgical site infection, were also increased for procedures lasting >120 minutes. In a multivariable analysis, operative time exceeding 120 minutes remained an independent predictor of any complication and wound complication, with each 30-minute increase in operative time beyond 120 minutes further increasing risk. Patient age ≤65 years, male sex, black race, BMI ≥ 30 kg/m2 , and an ASA classification of 3 or 4 all predicted operative times >120 minutes. Conclusions We found that operative time >120 minutes was associated with increased short-term morbidity and mortality following primary TJA. Younger age, male sex, black race, obesity, and increased comorbidity were risk factors for operative time exceeding 120 minutes.
Background and Aims Extension of ampullary adenomas into the common bile duct (CBD) or pancreatic duct (PD) may be difficult to treat endoscopically. We evaluated the feasibility, safety, and ...efficacy of endoscopic radiofrequency ablation (RFA) in the management of ampullary neoplasms with intraductal extension. Methods This was a multicenter, retrospective analysis of all patients with intraductal extension of ampullary neoplasms treated with endoscopic RFA between February 2012 and June 2015. Treatment success was defined as the absence of detectable intraductal polyps by ductography, visual inspection, and biopsy sampling. Results Fourteen patients with adenoma extension into the CBD (13 ± 7 mm, n = 14) and PD (7 ± 2 mm, n = 3) underwent a median of 1 RFA sessions (range, 1-5). Additional modalities (thermal probes, argon plasma coagulation, and/or photodynamic therapy) were also used in 7 patients, and prophylactic stents were routinely placed. Thirteen assessable patients underwent a median of 2 surveillance ERCPs after completion of treatment over a median follow-up of 16 months (range, 5-46), with intraductal biopsy specimens showing no neoplasm in 12 patients at the conclusion of endoscopic treatment. Treatment success was achieved in 92%, including 100% of those treated with RFA alone. Adverse events occurred in 43% and included ductal strictures (5 patients) and retroduodenal abscess (1 patient), all of which were successfully treated endoscopically. Conclusions Endoscopic RFA, alone or in combination with other modalities, may effectively treat intraductal extension of ampullary neoplasms. Ductal strictures were common after RFA but responded to endoscopic stent therapy. RFA may be appropriate in selected patients, particularly when the main treatment alternative is pancreaticoduodenectomy.
Abstract The authors assessed the incidence of and risk factors associated with 30-day surgical site infections (SSIs) following primary (p) and revision (r) THA and TKA. In total, 23,128 primary and ...2170 revision TJAs were identified between 2005 and 2010 in the ACS NSQIP database. The 30-day SSI rates, overall and deep, were 1.1 and 0.1% for pTKA, 1.18 and 0.4% for pTHA, 1.68 and 0.7% for rTKA, and 2.9 and 1.7% for rTHA. After primary TJA, independent risk factors were BMI > 40, hypertension, prolonged operative time, electrolyte disturbance and previous infection, and after revision TJA, dyspnea and bleeding disorder were risk factors. This study should help provide benchmark data for SSI following TJA.
Summary Background With recent improvements in vaccines and treatments against viral hepatitis, an improved understanding of the burden of viral hepatitis is needed to inform global intervention ...strategies. We used data from the Global Burden of Disease (GBD) Study to estimate morbidity and mortality for acute viral hepatitis, and for cirrhosis and liver cancer caused by viral hepatitis, by age, sex, and country from 1990 to 2013. Methods We estimated mortality using natural history models for acute hepatitis infections and GBD's cause-of-death ensemble model for cirrhosis and liver cancer. We used meta-regression to estimate total cirrhosis and total liver cancer prevalence, as well as the proportion of cirrhosis and liver cancer attributable to each cause. We then estimated cause-specific prevalence as the product of the total prevalence and the proportion attributable to a specific cause. Disability-adjusted life-years (DALYs) were calculated as the sum of years of life lost (YLLs) and years lived with disability (YLDs). Findings Between 1990 and 2013, global viral hepatitis deaths increased from 0·89 million (95% uncertainty interval UI 0·86–0·94) to 1·45 million (1·38–1·54); YLLs from 31·0 million (29·6–32·6) to 41·6 million (39·1–44·7); YLDs from 0·65 million (0·45–0·89) to 0·87 million (0·61–1·18); and DALYs from 31·7 million (30·2–33·3) to 42·5 million (39·9–45·6). In 2013, viral hepatitis was the seventh (95% UI seventh to eighth) leading cause of death worldwide, compared with tenth (tenth to 12th) in 1990. Interpretation Viral hepatitis is a leading cause of death and disability worldwide. Unlike most communicable diseases, the absolute burden and relative rank of viral hepatitis increased between 1990 and 2013. The enormous health loss attributable to viral hepatitis, and the availability of effective vaccines and treatments, suggests an important opportunity to improve public health. Funding Bill & Melinda Gates Foundation.
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