Safety and efficacy of EsoFLIP dilation in patients with esophageal dysmotility: a systematic review.

Esophageal manometry is utilized for the evaluation and classification of esophageal motility disorders. EndoFlip has been introduced as an adjunctive test to evaluate esophagogastric junction (EGJ) distensibility. Treatment options for achalasia and EGJ outflow obstruction (EGJOO) include pneumatic dilation, myotomy, and botulinum toxin. Recently, a therapeutic 30 mm hydrostatic balloon dilator (EsoFLIP, Medtronic, Minneapolis, MN, USA) has been introduced, which uses impedance planimetry technology like EndoFlip. We performed a systematic review to evaluate the safety and efficacy of EsoFLIP in the management of esophageal motility disorders. A systematic literature search was performed with Medline, Embase, Web of science, and Cochrane library databases from inception to November 2022 to identify studies utilizing EsoFLIP for management of esophageal motility disorders. Our primary outcome was clinical success, and secondary outcomes were adverse events. Eight observational studies including 222 patients met inclusion criteria. Diagnoses included achalasia (158), EGJOO (48), post-reflux surgery dysphagia (8), and achalasia-like disorder (8). All studies used 30 mm maximum balloon dilation except one which used 25 mm. The clinical success rate was 68.7%. Follow-up duration ranged from 1 week to a mean of 5.7 months. Perforation or tear occurred in four patients. EsoFLIP is a new therapeutic option for the management of achalasia and EGJOO and appears to be effective and safe. Future comparative studies with other therapeutic modalities are needed to understand its role in the management of esophageal motility disorders.

Early versus late endoscopic treatment of pancreatic necrotic collections: A systematic review and meta-analysis.

Background and study aims Recently studies have compared early (<4 weeks) vs. late or standard (>4 weeks) endoscopic treatment of pancreatic necrotic collections (PNC) and have reported favorable results for early treatment. In this meta-analysis, we compared the efficacy and safety of early vs. late endoscopic treatment of PNC. Patients and methods We reviewed several databases from inception to September 30, 2021 to identify studies that compared early with late endoscopic treatment of PNC. Our outcomes of interest were adverse events (AEs), resolution of PNC, performance of direct endoscopic necrosectomy, need for further interventions, and mean number of endoscopic necrosectomy sessions. We calculated pooled risk ratios (RRs) with 95% confidence intervals (CIs) for categorical variables and mean differences (MDs) with 95% CIs for continuous variables. Data were analyzed by random effect model. Heterogeneity was assessed by I 2 statistic. Results We included four studies with 427 patients. We found no significant difference in rates of AEs, RR (95% CI) 1.70 (range, 0.56-5.20), resolution of necrotic or fluid collections, RR (95% CI) 0.89 (range, 0.71-1.11), need for further interventions, RR (95% CI) 1.47 (range, 0.70-3.08), direct necrosectomy, RR (95% CI) 1.39 (range, 0.22-8.80), mortality, RR (95% CI) 2.37 (range, 0.26-21.72) and mean number of endoscopic necrosectomy sessions, MD (95% CI) 1.58 (range,-0.20-3.36) between groups. Conclusions Early endoscopic treatment of PNC can be considered for indications such as infected necrosis or sterile necrosis with symptoms or complications; however, future large multicenter studies are required to further evaluate its safety.

The Association of "Loss of Smell" to COVID-19: A Systematic Review and Meta-Analysis.

BACKGROUND: The presence of olfactory dysfunction or "loss of smell" has been reported as an atypical symptom in patients with coronavirus disease 2019 (COVID-19). We performed a systematic review and meta-analysis of the available literature to evaluate the prevalence of "loss of smell" in COVID-19 as well as its utility for prognosticating the disease severity. METHODS: An exhaustive search of the PubMed/Medline, Embase, Web of Science, Cochrane Library, LitCovid NIH, and WHO COVID-19 database was conducted through August 6th, 2020. All studies reporting the prevalence of "loss of smell" (anosmia and/or hyposmia/microsmia) in laboratory-confirmed COVID-19 patients were included. Pooled prevalence for cases (positive COVID-19 through reverse transcriptase (RT-PCR) and/or serology IgG/IgM) and controls (negative RT-PCR and/or serology) was compared, and the odds ratio (OR), 95% confidence interval (CI) and the p-value were calculated. A p-value of <0.05 was considered statistically significant. RESULTS: A total of 51 studies with 11074 confirmed COVID-19 patients were included. Of these, 21 studies used a control group with 3425 patients. The symptom of "loss of smell" (OR: 14.7, CI: 8.9-24.3) was significantly higher in the COVID-19 group when compared to the control group. Seven studies comparing severe COVID-19 patients with- and without "loss of smell" demonstrated favorable prognosis for patients with "loss of smell" (OR: 0.36, CI 0.27-0.48). CONCLUSIONS: Olfactory dysfunction or "loss of smell" is a prevalent symptom in COVID-19 patients. Moreover, COVID-19 patients with "loss of smell" appear to have a milder course of the disease.

Therapeutic targeting of immune checkpoints with small molecule inhibitors.

Immune checkpoints are known to contribute to tumor progression by enhancing cancer's ability to evade the immune system and metastasize. Immunotherapies, including monoclonal antibodies, have been developed to target specific immunosuppressive molecules on the membranes of cancer cells and have proven revolutionary in the field of oncology. Recently, small molecule inhibitors (SMIs) have gained increased attention in cancer research with potential applications in immunotherapy. SMIs have desirable benefits over large-molecule inhibitors, such as monoclonal antibodies, including greater cell permeability, organ specificity, longer half-lives, cheaper production costs, and the possibility for oral administration. This paper will review the mechanisms by which noteworthy and novel immune checkpoints contribute to tumor progression, and how they may be targeted by SMIs and epigenetic modifiers to offer possible adjuvants to established therapeutic regimens. SMIs target immune checkpoints in several ways, such as blocking signaling between tumorigenic factors, building immune tolerance, and direct inhibition via epigenetic repression of immune inhibitory molecules. Further investigation into combination therapies utilizing SMIs and conventional cancer therapies will uncover new treatment options that may provide better patient outcomes across a range of cancers.