Comparative Effectiveness of Fecal Immunochemical Tests versus Flexible Sigmoidoscopy for Colorectal Cancer Screening: A Systematic Review and Meta-Analysis of Randomized Clinical Trials.

BACKGROUND AND AIMS: Fecal immunochemical tests (FITs) and flexible sigmoidoscopies are commonly used modalities for colorectal cancer (CRC) screening. We performed a systematic review and meta-analysis to compare the effectiveness of FIT and sigmoidoscopy in CRC screening. METHODS: PRISMA statement and Cochrane guidelines were followed for this review. Digital dissertation databases were searched from inception till December 1st 2020 and randomized clinical trials comparing the detection rates of CRC for FIT and sigmoidoscopy were included. Outcomes for analysis included participation rates and detection rates of CRC, advanced adenomas and advanced colorectal neoplasia for both screening modalities. RESULTS: Five randomized clinical trials with a total of 261,755 patients were included for the analysis. The participation rate for FIT was significantly higher compared to flexible sigmoidoscopy (OR 2.11, 95% CI 1.29-3.44, p=0.003). In intention-to-screen analysis, the detection rate for advanced colorectal neoplasia was significantly lower with FIT (OR 0.62, 95% CI 0.45-0.84, p=0.002) as compared to flexible sigmoidoscopy but not statistically different for CRC (OR 1.15, 95% CI 0.65-2.02, p=0.63). CONCLUSION: Despite lower participation amongst patients, CRC screening with flexible sigmoidoscopy leads to higher detection of advanced colorectal neoplasia, when compared to a single round of fecal immunochemical testing.

Temporal trends and mortality of post-ERCP pancreatitis in the United States: a nationwide analysis.

BACKGROUND : Post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) is the most common and most serious complication of ERCP. Our aim was to estimate the nationwide incidence, temporal trends, and mortality of PEP in the United States and to establish risk factors associated with PEP development. METHODS : This was a retrospective cohort study analyzing Nationwide Inpatient Sample data from 2011 to 2017 using International Classification of Diseases codes. The primary outcomes were trends in PEP incidence and predictors of PEP development. Secondary outcomes were in-hospital mortality, length of hospital stay, and admission to the intensive care unit. RESULTS : Of 1 222 467 adult patients who underwent inpatient ERCP during the study period, 55 225 (4.5 %) developed PEP. The hospital admission rate of PEP increased by 15.3 %, from 7735 in 2011 to 8920 in 2017 (odds ratio [OR] 1.23, 95 % confidence interval [CI] 1.04 - 1.46; P = 0.02). The overall rate of mortality increased from 2.8 % of PEP cases in 2011 to 4.4 % in 2017 (OR 1.62, 95 %CI 1.10 - 2.38; P = 0.01). Multiple patient-related (alcohol use, cocaine use, obesity, chronic kidney disease, heart failure), procedure-related (therapeutic ERCP, sphincterotomy, pancreatic duct stent placement, sphincter of Oddi dysfunction), and hospital-related (teaching hospitals, hospitals located in the West and Midwest) factors that impact the occurrence of PEP were identified. CONCLUSIONS : Our study showed rising hospital admission and mortality rates associated with PEP in the United States. This calls for a greater recognition of this life-threatening complication and amelioration of its risk factors, whenever possible.

Efficacy of Hemospray in Upper Gastrointestinal Bleeding: A Systematic Review and Meta-Analysis.

BACKGROUND AND AIMS: Hemospray is a non-contact modality of endoscopic hemostasis that has been used in the management of upper gastrointestinal bleeding (UGIB) with varying success. Our aim was to evaluate the efficacy of Hemospray in the management of UGIB. METHODS: An electronic bibliographic search of digital dissertation databases was performed from inception till October 2019. All prospective studies, including randomized controlled trials evaluating the efficacy of Hemospray in the management of UGIB were analysed. The primary outcome was immediate haemostasis and the secondary outcome was rebleeding rate. Subgroup analyses based on etiology of UGIB (tumour-related, variceal, etc) were also performed. RESULTS: A total of 11 prospective studies, including 4 randomized trials were included for the analysis. The pooled immediate haemostasis rate with Hemospray was 93% (95% CI 90.3-95%, p<0.001). Rebleeding occurred in 14.4% (95% CI 8.8-22.8%, p<0.001) of patients. For the subgroup of tumour-related bleeding, the immediate haemostasis rate was 95.3% (95% CI 89.6-97.3%; p <0.001) and rebleeding rate was 21.9% (95% CI 13.9-32.7%, p <0.001). In patients with variceal bleeding, immediate haemostasis was achieved in 92.7% (95% CI 83.6-96.9%; p<0.001) of patients, with a rebleeding rate of 3.1% (95% CI 0.9-10.2%, p <0.001). CONCLUSION: Hemospray shows high immediate haemostasis and low bleeding percentages. The odds were in its favour compared to conventional endoscopic modalities, but not statistically significant. The results are undermined by the risk of bias in the studies. Nevertheless, it is an easy technique that should be further investigated with better studies.

Rifaximin versus norfloxacin for prevention of spontaneous bacterial peritonitis: a systematic review.

AIM: The aim of this systematic review is to evaluate the efficacy and safety of rifaximin in the prophylaxis of spontaneous bacterial peritonitis (SBP) as compared with norfloxacin. METHODS: We searched MEDLINE, CINAHL, Google Scholar and Cochrane databases from inception to January 2017. Reference lists of articles as well as conference proceedings were manually screened. We included studies that recruited patients with cirrhosis and ascites who met the criteria for primary or secondary SBP prophylaxis as defined by the European Association for the Study of the Liver and American Association for the Study of Liver Diseases. Two independent investigators reviewed the studies for eligibility, extracted the data and assessed study quality using the Cochrane risk of bias tool. The primary outcome was occurrence of SBP. Secondary outcomes included mortality and adverse events with therapy. RESULTS: Of the 435 studies identified, a total of five were included for full-text review. Four studies were eligible for the systematic review, three of which were randomised controlled trials and one was a prospective observational study. The population examined in majority of studies was primarily hepatitis C cirrhosis. The results of individual studies indicated either superior efficacy of rifaximin or no statistical difference between rifaximin and norfloxacin for SBP prophylaxis. CONCLUSIONS: Moderate-quality evidence shows that long-term use of rifaximin appears to be a reasonable alternative to norfloxacin for SBP prevention in hepatitis C cirrhosis.

SUMOylation regulates telomere length by targeting the shelterin subunit Tpz1(Tpp1) to modulate shelterin-Stn1 interaction in fission yeast.

Telomeres protect DNA ends of linear eukaryotic chromosomes from degradation and fusion, and ensure complete replication of the terminal DNA through recruitment of telomerase. The regulation of telomerase is a critical area of telomere research and includes cis regulation by the shelterin complex in mammals and fission yeast. We have identified a key component of this regulatory pathway as the SUMOylation [the covalent attachment of a small ubiquitin-like modifier (SUMO) to target proteins] of a shelterin subunit in fission yeast. SUMOylation is known to be involved in the negative regulation of telomere extension by telomerase; however, how SUMOylation limits the action of telomerase was unknown until now. We show that SUMOylation of the shelterin subunit TPP1 homolog in Schizosaccharomyces pombe (Tpz1) on lysine 242 is important for telomere length homeostasis. Furthermore, we establish that Tpz1 SUMOylation prevents telomerase accumulation at telomeres by promoting recruitment of Stn1-Ten1 to telomeres. Our findings provide major mechanistic insights into how the SUMOylation pathway collaborates with shelterin and Stn1-Ten1 complexes to regulate telomere length.