Esophageal cancer ranks sixth in cancer death. To explore its genetic origins, we conducted exomic sequencing on 11 esophageal adenocarcinomas (EAC) and 12 esophageal squamous cell carcinomas (ESCC) ...from the United States. Interestingly, inactivating mutations of NOTCH1 were identified in 21% of ESCCs but not in EACs. There was a substantial disparity in the spectrum of mutations, with more indels in ESCCs, A:T>C:G transversions in EACs, and C:G>G:C transversions in ESCCs (P < 0.0001). Notably, NOTCH1 mutations were more frequent in North American ESCCs (11 of 53 cases) than in ESCCs from China (1 of 48 cases). A parallel analysis found that most mutations in EACs were already present in matched Barrett esophagus. These discoveries highlight key genetic differences between EACs and ESCCs and between American and Chinese ESCCs, and suggest that NOTCH1 is a tumor suppressor gene in the esophagus. Finally, we provide a genetic basis for the evolution of EACs from Barrett esophagus.
Clostridium difficile infection (CDI) is the most common healthcare associated infection and is highly prevalent in Europe and North America. Limited data is available on the prevalence of CDI in ...Asia. However, secular increases in prevalence of risk factors for CDI suggest that it may be emerging as a major cause of morbidity, highlighting the urgent need for a systematic study of the prevalence of CDI in Asia.
We systematically searched PubMed/Medline and Embase for publications from Asia between 2000-16 examining prevalence of CDI. A random-effects meta-analysis was performed to calculate the pooled prevalence of CDI in Asia and to identify subgroups and regions at high risk.
Our meta-analysis included 51 studies from throughout Asia including 37,663 patients at risk among whom confirmed CDI was found in 4,343 patients. The pooled proportion of confirmed CDI among all patients with diarrhea was 14.8% with a higher prevalence in East Asia (19.5%), compared with South Asia (10.5%) or the Middle East (11.1%). There were an estimated 5.3 episodes of CDI per 10,000 patient days, similar to rates reported from Europe and North America. Infections due to hypervirulent strains were rare. CDI-related mortality was 8.9%.
In a meta-analysis of 51 studies, we observed similar rates of CDI in Asia in comparison to Europe and North America. Increased awareness and improved surveillance of Clostridium difficile is essential to reduce incidence and morbidity.
Placement of a pancreatic stent is recommended for the prevention of pancreatitis after endoscopic retrograde cholangiopancreatitis (ERCP) among high-risk patients. However, it is not known whether ...there is a particular feature of the pancreatic stent that is associated with a lower incidence of post-ERCP pancreatitis (PEP). This systematic review and network meta-analysis (NMA) aimed to examine whether a particular feature of pancreatic stents is associated with lower incidence of PEP.
The MEDLINE, Embase, and Cochrane Library databases were searched for randomized controlled trials (RCTs) that evaluated the efficacy of pancreatic stents in the prevention of PEP from September 1993 to June 2013. Trials that reported the incidence of PEP in high-risk patients randomized to one vs. another type of pancreatic stent or vs. no stent at all were included in the analysis.
Among the 1377 citations identified from the database searches, 6 RCTs involving 561 patients were included. Three RCTs evaluated 5-Fr straight, flanged pancreatic stents, two RCTs evaluated 5-Fr single-pigtail, unflanged stents, and three RCTs evaluated 3-Fr single-pigtail, unflanged stents. The probability of being ranked the best was 50.3 % (SD = 0.5, Markov chain error = 0.003) for 5-Fr single-pigtail, unflanged pancreatic stents, 46.5 % for 5-Fr straight, flanged stents, and 3.1 % for 3-Fr single-pigtail, unflanged stents.
The 5-Fr pancreatic stent is superior to the 3-Fr pancreatic stent for the prevention of PEP in high-risk patients. The 5-Fr single-pigtail, unflanged pancreatic stent and 5-Fr straight, flanged pancreatic stent performed similarly and both performed better than the 3-Fr pancreatic stent in preventing PEP, suggesting that stent diameter is more important for the prevention of PEP than type of stent or the presence of flanges.
Background Endoscopic drainage (ED) and percutaneous drainage (PD) have largely replaced surgical drainage as the initial approach for symptomatic pseudocysts. However, there are few studies ...comparing ED and PD. Objective To compare the outcomes of ED and PD for symptomatic pseudocysts. Design Retrospective cohort study. Setting Academic center. Patients Adult patients with symptomatic pseudocysts within ≤1 cm of the gastric or duodenal wall who underwent ED or PD between 1993 and 2011. Patients with walled-off pancreatic necrosis were excluded. Intervention ED or PD. Main Outcome Measurements Rates of technical success, procedural adverse events, clinical success, reinterventions, and failure. Other outcomes included the length of hospital stay and number of follow-up abdominal imaging studies. Results There were 81 patients, 41 who underwent ED and 40 who underwent PD, with no differences in age, sex, and comorbidity between the 2 groups. There were no differences in the rates of technical success (90.2% vs 97.5%; P = .36), adverse events (14.6% vs 15%; P = .96), and clinical success (70.7% vs 72.5%; P = .86) between ED and PD, respectively. Patients who underwent PD had higher rates of reintervention (42.5% vs 9.8%; P = .001), longer length of hospital stay (14.8 ± 14.4 vs 6.5 ± 6.7 days; P = .001), and median number quartiles of follow-up abdominal imaging studies (6 3.25, 10 vs 4 2.5, 6; P = .02) compared with patients who underwent ED. Limitations Single center, retrospective study. Conclusion ED and PD have similar clinical success rates for symptomatic pseudocysts. However, PD is associated with significantly higher rates of reintervention, longer length of hospital stay, and increased number of follow-up abdominal imaging studies.
Consumption of chocolate has been often hypothesized to reduce the risk of cardiovascular disease (CVD) due to chocolate's high levels of stearic acid and antioxidant flavonoids. However, debate ...still lingers regarding the true long term beneficial cardiovascular effects of chocolate overall.
We reviewed English-language MEDLINE publications from 1966 through January 2005 for experimental, observational, and clinical studies of relations between cocoa, cacao, chocolate, stearic acid, flavonoids (including flavonols, flavanols, catechins, epicatechins, and procynadins) and the risk of cardiovascular disease (coronary heart disease (CHD), stroke). A total of 136 publications were selected based on relevance, and quality of design and methods. An updated meta-analysis of flavonoid intake and CHD mortality was also conducted.
The body of short-term randomized feeding trials suggests cocoa and chocolate may exert beneficial effects on cardiovascular risk via effects on lowering blood pressure, anti-inflammation, anti-platelet function, higher HDL, decreased LDL oxidation. Additionally, a large body of trials of stearic acid suggests it is indeed cholesterol-neutral. However, epidemiologic studies of serum and dietary stearic acid are inconclusive due to many methodologic limitations. Meanwhile, the large body of prospective studies of flavonoids suggests the flavonoid content of chocolate may reduce risk of cardiovascular mortality. Our updated meta-analysis indicates that intake of flavonoids may lower risk of CHD mortality, RR = 0.81 (95% CI: 0.71-0.92) comparing highest and lowest tertiles.
Multiple lines of evidence from laboratory experiments and randomized trials suggest stearic acid may be neutral, while flavonoids are likely protective against CHD mortality. The highest priority now is to conduct larger randomized trials to definitively investigate the impact of chocolate consumption on long-term cardiovascular outcomes.
The objective of this study was to assess inflammatory bowel disease (IBD) medications in relation to lymphoma risk.
Information on IBD and relevant medications and other utilization was obtained ...from the Kaiser Permanente IBD Registry, 1996-2009. Lymphoma cases were ascertained from the Kaiser Permanente Cancer Registry. Lymphoma incidence was compared between the IBD cohort and the general Kaiser Permanente population.
Of the 16,023 IBD patients without human immunodeficiency virus followed an average 5.8 years, 43 developed lymphoma. IBD patients with and without lymphoma did not differ with respect to past IBD-related visits, procedures, or tests. The standardized incidence rate ratio (SIRR) for lymphoma among IBD patients with no dispensing of thiopurine or anti-tumor necrosis factor (TNF) was 1.0 (95% confidence interval (CI): 0.96-1.1). Of the 21,282 person-years involving exposure to thiopurine or anti-TNF, 81% involved thiopurine alone; 3%, anti-TNF alone; and 16%, combination therapy. Among patients with thiopurine but not anti-TNF dispensings, the SIRR was 0.3 (95% CI: 0.2-0.4) for past use and 1.4 for current use (95% CI: 1.2-2.7). Among patients with dispensing of anti-TNF (with and without thiopurine), the SIRR was 5.5 for past use (95% CI: 4.5-6.6) and 4.4 for current use (95% CI: 3.4-5.4). The most common lymphoma subtypes were diffuse large B-cell lymphoma (44%), follicular lymphoma (14%), and Hodgkin's disease (12%).
Our study provides evidence that IBD alone is not associated with the risk of lymphoma. Use of anti-TNF with thiopurine and current use of thiopurine alone were associated with increased risk, although the effect of disease severity merits further evaluation.
Given the increase in medications for type 2 diabetes mellitus, clinicians and patients need information about their effectiveness and safety to make informed choices.
To summarize the benefits and ...harms of metformin, second-generation sulfonylureas, thiazolidinediones, meglitinides, dipeptidyl peptidase-4 (DPP-4) inhibitors, and glucagon-like peptide-1 receptor agonists, as monotherapy and in combination, to treat adults with type 2 diabetes.
MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials were searched from inception through April 2010 for English-language observational studies and trials. The MEDLINE search was updated to December 2010 for long-term clinical outcomes.
Two reviewers independently screened reports and identified 140 trials and 26 observational studies of head-to-head comparisons of monotherapy or combination therapy that reported intermediate or long-term clinical outcomes or harms.
Two reviewers following standardized protocols serially extracted data, assessed applicability, and independently evaluated study quality.
Evidence on long-term clinical outcomes (all-cause mortality, cardiovascular disease, nephropathy, and neuropathy) was of low strength or insufficient. Most medications decreased the hemoglobin A(1c) level by about 1 percentage point and most 2-drug combinations produced similar reductions. Metformin was more efficacious than the DPP-4 inhibitors, and compared with thiazolidinediones or sulfonylureas, the mean differences in body weight were about -2.5 kg. Metformin decreased low-density lipoprotein cholesterol levels compared with pioglitazone, sulfonylureas, and DPP-4 inhibitors. Sulfonylureas had a 4-fold higher risk for mild or moderate hypoglycemia than metformin alone and, in combination with metformin, had more than a 5-fold increased risk compared with metformin plus thiazolidinediones. Thiazolidinediones increased risk for congestive heart failure compared with sulfonylureas and increased risk for bone fractures compared with metformin. Diarrhea occurred more often with metformin than with thiazolidinediones.
Only English-language publications were reviewed. Some studies may have selectively reported outcomes. Many studies were small, were of short duration, and had limited ability to assess clinically important harms and benefits.
Evidence supports metformin as a first-line agent to treat type 2 diabetes. Most 2-drug combinations similarly reduce hemoglobin A(1c) levels, but some increased risk for hypoglycemia and other adverse events.
Agency for Healthcare Research and Quality.
Uninsured and insured but out-of-network emergency department (ED) patients are often billed hospital chargemaster prices, which exceed amounts typically paid by insurers.
To examine the variation in ...excess charges for services provided by emergency medicine and internal medicine physicians.
Retrospective analysis was conducted of professional fee payment claims made by the Centers for Medicare & Medicaid Services for all services provided to Medicare Part B fee-for-service beneficiaries in calendar year 2013. Data analysis was conducted from January 1 to July 31, 2016.
Markup ratios for ED and internal medicine professional services, defined as the charges submitted by the hospital divided by the Medicare allowable amount.
Our analysis included 12 337 emergency medicine physicians from 2707 hospitals and 57 607 internal medicine physicians from 3669 hospitals in all 50 states. Services provided by emergency medicine physicians had an overall markup ratio of 4.4 (340% excess charges), which was greater than the markup ratio of 2.1 (110% excess charges) for all services performed by internal medicine physicians. Markup ratios for all ED services ranged by hospital from 1.0 to 12.6 (median, 4.2; interquartile range IQR, 3.3-5.8); markup ratios for all internal medicine services ranged by hospital from 1.0 to 14.1 (median, 2.0; IQR, 1.7-2.5). The median markup ratio by hospital for ED evaluation and management procedure codes varied between 4.0 and 5.0. Among the most common ED services, laceration repair had the highest median markup ratio (7.0); emergency medicine physician review of a head computed tomographic scan had the greatest interhospital variation (range, 1.6-27.7). Across hospitals, markups in the ED were often substantially higher than those in the internal medicine department for the same services. Higher ED markup ratios were associated with hospital for-profit ownership (median, 5.7; IQR, 4.0-7.1), a greater percentage of uninsured patients seen (median, 5.0; IQR, 3.5-6.7 for ≥20% uninsured), and location (median, 5.3; IQR, 3.8-6.8 for the southeastern United States).
Across hospitals, there is wide variation in excess charges on ED services, which are often priced higher than internal medicine services. Our results inform policy efforts to protect uninsured and out-of-network patients from highly variable pricing.
Cholecystectomy during or within 4 weeks of hospitalization for acute biliary pancreatitis is recommended by guidelines. We examined adherence to the guidelines for incident mild-to-moderate acute ...biliary pancreatitis and the effectiveness of cholecystectomy to prevent recurrent episodes of pancreatitis.
Individuals in the 2010-2013 MarketScan Commercial Claims & Encounters database with a hospitalization associated with International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes of 577.0 for acute pancreatitis and 574.x for gallstone disease were eligible. Guideline adherence was considered cholecystectomy within 30 days of the first/index hospitalization for biliary pancreatitis. Individuals with and without guideline-adherent cholecystectomy were compared for subsequent hospitalization for acute or chronic pancreatitis using a Cox proportional hazards model adjusted for age, sex, comorbidities, and length of index hospital stay.
Of the 17,010 patients who met the inclusion criteria, 78% were adherent with the guidelines, including 10,918 who underwent cholecystectomy during the index hospitalization and 2,387 who underwent cholecystectomy within 30 days. Among 3,705 patients non-adherent with the guidelines, 1,213 had a cholecystectomy 1-6 months after the index hospitalization. Guideline-adherent cholecystectomy resulted in fewer subsequent hospitalizations for acute and chronic pancreatitis as compared with non-adherence to the guidelines (acute pancreatitis: 3% vs. 13%, P<0.001; chronic pancreatitis: 1% vs. 4%, P<0.001).
Nearly four out of five patients underwent cholecystectomy for acute biliary pancreatitis in a timeframe, consistent with guidelines. Adherence resulted in a decrease in subsequent hospitalizations for both acute and chronic pancreatitis. However, the majority of non-adherent patients did not undergo a subsequent cholecystectomy. There may be factors that predict the need for immediate vs. delayed cholecystectomy.
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