Systematic review and meta-analysis of effectiveness of treatment options against SARS-CoV-2 infection

Treatment options for severe acute respiratory syndrome-related coronavirus-2 (SARS-CoV-2) are limited with no clarity on efficacy and safety profiles. We performed a systematic review and meta-analysis of studies on patients ≥18 years reporting data on therapeutic interventions in SARS-CoV-2. Primary outcome was all-cause mortality and secondary outcomes were rates of mechanical ventilation, viral clearance, adverse events, discharge, and progression to severe disease. Pooled rates and odds ratios (OR) were calculated. Twenty-nine studies with 5207 patients were included. Pooled all-cause mortality in intervention arm was 12.8% (95% confidence interval [CI]: 8.1%-17.4%). Mortality was significantly higher for studies using hydroxychloroquine (HCQ) for intervention (OR: 1.36; 95% CI: 0.97-1.89). Adverse events were also higher in HCQ subgroup (OR: 3.88; 95% CI: 1.60-9.45). There was no difference in other secondary outcomes. There is a need for well-designed randomized clinical trials for further investigation of every therapeutic intervention for further insight into different therapeutic options

Second-generation distal attachment cuff improves adenoma detection rate: meta-analysis of randomized controlled trials

Background and Aims Multiple randomized controlled trials (RCTs) using the second-generation distal attachment cuff device (Endocuff Vision; Olympus America, Center Valley, Pa, USA) have reported conflicting results in improving adenoma detection rate (ADR) compared with standard high-definition colonoscopy without the distal attachment. We conducted a systematic review and meta-analysis of RCTs to compare outcomes between second-generation cuff colonoscopy (CC) versus colonoscopy without the distal attachment (standard colonoscopy [SC]). Methods An electronic literature search was performed using PubMed, Google Scholar, Embase, and Cochrane Library through May 2020. The primary outcome was reporting of ADR, and secondary outcomes were polyp detection rate (PDR), mean withdrawal time, mean adenomas per colonoscopy (APC), sessile serrated lesion detection rate, and adverse events. Pooled rates and risk ratios (RRs) with 95% confidence intervals were reported. Results Eight RCTs with 5695 patients were included in the final analysis, with 2862 patients (mean age, 62.8 years; 52.9% men) in the CC group and 2833 patients (mean age, 62.6 years; 54.2% men) in the SC group. Compared with SC, use of CC was associated with a significant improvement in ADR (49.8% vs 45.6%, respectively; RR, 1.12; P = .02), PDR (58.1% vs 53%, respectively; RR, 1.12; P = .009), and APC ( P < .01). Furthermore, use of CC had a .93-minute lower mean withdrawal time ( P < .01) when compared with SC. The difference in ADR was larger in the screening/surveillance population (6.5%, P = .02) and when used by endoscopists with ADRs <30% (9.4%, P = .03). Conclusions The results of this meta-analysis of randomized trials show a significant improvement in ADR and APC with shorter withdrawal times using the second-generation cuff device compared with SC

Prophylactic Clipping After Colorectal Endoscopic Resection Prevents Bleeding of Large, Proximal Polyps: Meta-Analysis of Randomized Trials

Background & Aims The benefits of prophylactic clipping to prevent bleeding after polypectomy are unclear. We conducted an updated meta-analysis of randomized trials to assess the efficacy of clipping in preventing bleeding after polypectomy, overall and according to polyp size and location. Methods We searched the Medline/PubMed, EMBASE, and Scopus databases randomized trials that compared effects of clipping vs not clipping to prevent bleeding after polypectomy. We performed a random-effects meta-analysis to generate pooled relative risks (RRs) with 95% CIs. Multilevel random-effects meta-regression analysis was used to combine data on bleeding after polypectomy and estimate associations between rates of bleeding and polyp characteristics. Results We analyzed data from 9 trials, comprising 7197 colorectal lesions (22.5% 20 mm or larger, 49.2% with proximal location). Clipping, compared with no clipping, did not significantly reduce the overall risk of post-polypectomy bleeding (2.2% with clipping vs 3.3% with no clipping; RR, 0.69; 95% CI, 0.45–1.08; P=.072). Clipping significantly reduced risk of bleeding after removal of polyps that were 20 mm or larger (4.3% had bleeding after clipping vs 7.6% had bleeding with no clipping; RR, 0.51; 95% CI, 0.33–0.78; P=.020) or that were in a proximal location (3.0% had bleeding after clipping vs 6.2% had bleeding with no clipping; RR, 0.53; 95% CI, 0.35–0.81; P<.001). In multilevel meta-regression analysis that adjusted for polyp size and location, prophylactic clipping was significantly associated with reduced risk of bleeding after removal of large proximal polyps (RR, 0.37; 95% CI, 0.22–0.61; P=.021) but not small proximal lesions (RR, 0.88; 95% CI, 0.48–1.62; P=0.581). Conclusions In a meta-analysis of randomized trials, we found that routine use of prophylactic clipping does not reduce risk of post-polypectomy bleeding, overall. However, clipping appeared to reduce bleeding after removal of large (more than 20 mm), proximal lesions

An SF1 affinity model to identify branch point sequences in human introns

Splicing factor 1 (SF1) binds to the branch point sequence (BPS) of mammalian introns and is believed to be important for the splicing of some, but not all, introns. To help identify BPSs, particularly those that depend on SF1, we generated a BPS profile model in which SF1 binding affinity data, validated by branch point mapping, were iteratively incorporated into computational models. We searched a data set of 117 499 human introns for best matches to the SF1 Affinity Model above a threshold, and counted the number of matches at each intronic position. After subtracting a background value, we found that 87.9% of remaining high-scoring matches identified were located in a region upstream of 3′-splice sites where BPSs are typically found. Since U2AF65 recognizes the polypyrimidine tract (PPT) and forms a cooperative RNA complex with SF1, we combined the SF1 model with a PPT model computed from high affinity binding sequences for U2AF65. The combined model, together with binding site location constraints, accurately identified introns bound by SF1 that are candidates for SF1-dependent splicing

Performance of artificial intelligence for colonoscopy regarding adenoma and polyp detection: a meta-analysis

BACKGROUND AND AIMS One fourth of colorectal neoplasia is missed at screening colonoscopy, representing the main cause of interval colorectal cancer (CRC). Deep learning systems with real-time computer-aided polyp detection (CADe) showed high accuracy in artificial settings, and preliminary randomized clinical trials (RCT) reported favourable outcomes in clinical setting. Aim of this meta-analysis was to summarise available RCTs on the performance of CADe systems in colorectal neoplasia detection. METHODS We searched MEDLINE, EMBASE and Cochrane Central databases until March 2020 for RCTs reporting diagnostic accuracy of CADe systems in detection of colorectal neoplasia. Primary outcome was pooled adenoma detection rate (ADR), Secondary outcomes were adenoma per colonoscopy (APC) according to size, morphology and location, advanced APC (AAPC), as well as polyp detection rate (PDR), Polyp-per-colonoscopy (PPC), and sessile serrated lesion per colonoscopy (SPC). We calculated risk ratios (RR), performed subgroup, and sensitivity analysis, assessed heterogeneity, and publication bias. RESULTS Overall, 5 randomized controlled trials (4354 patients), were included in the final analysis. Pooled ADR was significantly higher in the CADe groups than in the control group (791/2163, 36.6% vs 558/2191, 25.2%; RR, 1.44; 95% CI, 1.27-1.62; p10 mm adenomas (RR, 1.46; 95% CI, 1.04-2.06), as well as for proximal (RR, 1.59; 95% CI, 1.34-1.88) and distal (RR, 1.68; 95% CI, 1.50-1.88), and for flat (RR: 1.78 95% CI 1.47-2.15) and polypoid morphology (RR, 1.54; 95% CI, 1.40-1.68). Regarding histology, CADe resulted in a higher SPC (RR, 1.52; 95% CI,1.14-2.02), whereas a nonsignificant trend for AADR was found (RR, 1.35; 95% CI, 0.74 – 2.47; p = 0.33; I 2:69%). Level of evidence for RCTs was graded moderate. CONCLUSIONS According to available evidence, the incorporation of Artificial Intelligence as aid for detection of colorectal neoplasia results in a significant increase of the detection of colorectal neoplasia, and such effect is independent from main adenoma characteristics

Biophysical Characterization and Membrane Interaction of the Two Fusion Loops of Glycoprotein B from Herpes Simplex Type I Virus

The molecular mechanism of entry of herpesviruses requires a multicomponent fusion system. Cell invasion by Herpes simplex virus (HSV) requires four virally encoded glycoproteins: namely gD, gB and gH/gL. The role of gB has remained elusive until recently when the crystal structure of HSV-1 gB became available and the fusion potential of gB was clearly demonstrated. Although much information on gB structure/function relationship has been gathered in recent years, the elucidation of the nature of the fine interactions between gB fusion loops and the membrane bilayer may help to understand the precise molecular mechanism behind herpesvirus-host cell membrane fusion. Here, we report the first biophysical study on the two fusion peptides of gB, with a particular focus on the effects determined by both peptides on lipid bilayers of various compositions. The two fusion loops constitute a structural subdomain wherein key hydrophobic amino acids form a ridge that is supported on both sides by charged residues. When used together the two fusion loops have the ability to significantly destabilize the target membrane bilayer, notwithstanding their low bilayer penetration when used separately. These data support the model of gB fusion loops insertion into cholesterol enriched membranes

Efficacy and Tolerability of High- vs Low-Volume Split-Dose Bowel Cleansing Regimens for Colonoscopy: A Systematic Review and Meta-analysis

Background & Aims Efficacy of bowel preparation is an important determinant of outcomes of colonoscopy. It is not clear whether approved low-volume polyethylene glycol (PEG) and non-PEG regimens are as effective as high-volume PEG regimens when taken in a split dose. Methods In a systematic review of multiple electronic databases through January 31, 2019 with a registered protocol (PROSPERO: CRD42019128067), we identified randomized controlled trials that compared low- vs high-volume bowel cleansing regimens, administered in a split dose, for colonoscopy. The primary efficacy outcome was rate of adequate bowel cleansing, and the secondary efficacy outcome was adenoma detection rate. Primary tolerability outcomes were compliance, tolerability, and willingness to repeat. We calculated relative risk (RR) and 95% CI values and assessed heterogeneity among studies by using the I2 statistic. The overall quality of evidence was assessed using the GRADE framework. Results In an analysis of data from 17 randomized controlled trials, comprising 7528 patients, we found no significant differences in adequacy of bowel cleansing between the low- vs high-volume split-dose regimens (86.1% vs 87.4%; RR, 1.00; 95% CI, 0.98–1.02) and there was minimal heterogeneity (I2 = 17%). There was no significant difference in adenoma detection rate (RR, 0.96; 95% CI, 0.87–1.08) among 4 randomized controlled trials. Compared with high-volume, split-dose regimens, low-volume split-dose regimens had higher odds for compliance or completion (RR, 1.06; 95% CI, 1.02–1.10), tolerability (RR, 1.39; 95% CI, 1.12–1.74), and willingness to repeat bowel preparation (RR, 1.41; 95% CI, 1.20–1.66). The overall quality of evidence was moderate. Conclusions Based on a systematic review of 17 randomized controlled trials, low-volume, split-dose regimens appear to be as effective as high-volume, split-dose regimens in bowel cleansing and are better tolerated, with superior compliance

PDE4 Inhibition and Inflammatory Bowel Disease: A Novel Therapeutic Avenue

Background. In the last few decades, a better knowledge of the inflammatory pathways involved in the pathogenesis of Inflammatory Bowel Disease (IBD) has promoted biological therapy as an important tool to treat IBD patients. However, in spite of a wider spectrum of biological drugs, a significant proportion of patients is unaffected by or lose their response to these compounds, along with increased risks of infections and malignancies. For these reasons there is an urgent need to look for new pharmacological targets. The novel Phosphodiesterase 4 (PDE4) inhibitors have been recently introduced as new modulators of intracellular signals and gene transcription for the treatment of IBD. Aim. To discuss and describe the state of the art of this new class of compounds in the IBD field, with particular attention to apremilast. Methods. Published articles selected from PubMed were comprehensively reviewed, with key words including apremilast, inflammatory disease, IBD, psoriasis, psoriatic arthritis, pathogenesis, therapies, and treatment. Results. PDE4 inhibitors generate elevated intracellular levels of cyclic Adenosine Monophosphate (cAMP), that consequently down-regulate the release of pro-inflammatory cytokines in the mucosa of IBD patients. The newly developed apremilast is one of these drugs and has already been approved for the treatment of dermatologic/rheumatologic inflammatory conditions; studies in psoriasis and psoriatic arthritis have in fact demonstrated its clinical activity. However, no clinical trials have yet been published on the use of apremilast in IBD. Conclusion. In light of the similarity of pro-inflammatory signaling pathways across the gut, the skin, and joints, apremilast is likely supposed to show its efficacy also in IBD