Antibiotic prophylaxis to prevent complications in endoscopic retrograde cholangiopancreatography:A systematic review and meta-analysis of randomized controlled trials

BACKGROUND The prophylactic use of antibiotics in endoscopic retrograde cholangiopancreatography(ERCP)is still controversial.AIM To assess whether antibiotic prophylaxis reduces the rates of complications in patients undergoing elective ERCP.METHODS This systematic review and meta-analysis were performed following the Preferred Reporting Items for Systematic Reviews and Meta-analysis guidelines.A comprehensive search of multiple electronic databases was performed.Only randomized controlled trials were included.The outcomes analyzed included bacteremia,cholangitis,sepsis,pancreatitis,and mortality.The risk of bias was assessed by the Cochrane revised Risk-of-Bias tool for randomized controlled trials.The quality of evidence was assessed by the Grading of Recommendation Assessment,Development,and Evaluation.Meta-analysis was performed using the Review Manager 5.4 software.RESULTS Ten randomized controlled trials with a total of 1757 patients that compared the use of antibiotic and non-antibiotic prophylaxis in patients undergoing elective ERCP were included.There was no significant difference between groups regarding incidence of cholangitis after ERCP[risk difference(RD)=-0.02,95%confidence interval(CI):-0.05,0.02,P=0.32,cholangitis in patients with suspected biliary obstruction(RD=0.02,95%CI:-0.08 to 0.13,P=0.66),cholangitis on intravenous antibiotic prophylaxis(RD=-0.02,95%CI:-0.05 to 0.01,P=0.25),septicemia(RD=-0.02,95%CI:-0.06 to 0.01,P=0.25),pancreatitis(RD=-0.02,95%CI:-0.06 to 0.01,P=0.19),and allcause mortality(RD=0.00,95%CI:-0.01 to 0.01,P=0.71).However,the antibiotic prophylaxis group presented a 7%risk reduction in the incidence of bacteremia(RD=-0.07,95%CI:-0.14 to-0.01,P=0.03).CONCLUSION The prophylactic use of antibiotics in patients undergoing elective ERCP reduces the risk of bacteremia but does not appear to have an impact on the rates of cholangitis,septicemia,pancreatitis,and mortality.

Differential effectiveness of COVID-19 health behaviors:The role of mental health conditions in mask-wearing,social distancing,and hygiene practice

Background:Mental health conditions are known to increase susceptibility to infectious diseases,including coronavirus disease 2019(COVID-19).Health behaviors play a crucial role in mitigating this susceptibility.We aim to examine the differential effectiveness of COVID-19 preventive health behaviors among individuals,considering the presence or absence of specific mental health disorders.Methods:Multivariable logistic regression with interaction terms was performed to examine whether associations between adherence to health behaviors and COVID-19 infection were conditional on depression,anxiety,or eating disorders in a national sample of adults(N=61,891)from 140 US universities,2020–2021.Results:Adjusting for age,race/ethnicity,and gender/sex,the effectiveness of mask-wearing was significant and comparable among individuals with and without depression,anxiety,or eating disorders.Social distancing provided significantly less protection among individuals with depression,anxiety,or eating disorders.Hygiene practice provided significantly less protection among individuals with anxiety.Conclusion:Mask-wearing is robustly effective in the prevention of COVID-19 among individuals.However,social distancing and hygiene practice provide less significant protection among individuals with certain mental health conditions,suggesting the importance of prioritizing these individuals for additional preventive measures(e.g.,vaccines targeting variants)and mitigation strategies(e.g.,financial assistance,targeted mental health care,health education).

Peroral endoscopic myotomy vs laparoscopic myotomy and partial fundoplication for esophageal achalasia: A single-center randomized controlled trial

BACKGROUND Achalasia is a rare benign esophageal motor disorder characterized by incomplete relaxation of the lower esophageal sphincter(LES). The treatment of achalasia is not curative, but rather is aimed at reducing LES pressure. In patients who have failed noninvasive therapy, surgery should be considered. Myotomy with partial fundoplication has been considered the first-line treatment for non-advanced achalasia. Recently, peroral endoscopic myotomy(POEM), a technique that employs the principles of submucosal endoscopy to perform the equivalent of a surgical myotomy,has emerged as a promising minimally invasive technique for the management of this condition.AIM To compare POEM and laparoscopic myotomy and partial fundoplication(LM-PF) regarding their efficacy and outcomes for the treatment of achalasia.METHODS Forty treatment-naive adult patients who had been diagnosed with achalasia based on clinical and manometric criteria(dysphagia score ≥ II and Eckardt score > 3) were randomized to undergo either LM-PF or POEM. The outcome measures were anesthesia time, procedure time, symptom improvement, reflux esophagitis(as determined with the Gastroesophageal Reflux Disease Questionnaire), barium column height at 1 and 5 min(on a barium esophagogram), pressure at the LES, the occurrence of adverse events(AEs), length of stay(LOS), and quality of life(QoL).RESULTS There were no statistically significant differences between the LM-PF and POEM groups regarding symptom improvement at 1, 6, and 12 mo of follow-up(P = 0.192, P = 0.242, and P = 0.242, respectively). However, the rates of reflux esophagitis at 1, 6, and 12 mo of follow-up were significantly higher in the POEM group(P = 0.014, P < 0.001, and P = 0.002, respectively). There were also no statistical differences regarding the manometry values, the occurrence of AEs, or LOS. Anesthesia time and procedure time were significantly shorter in the POEM group than in the LM-PF group(185.00 ± 56.89 and 95.70 ± 30.47 min vs 296.75 ± 56.13 and 218.75 ± 50.88 min,respectively;P = 0.001 for both). In the POEM group, there were improvements in all domains of the QoL questionnaire, whereas there were improvements in only three domains in the LM-PF group.CONCLUSION POEM and LM-PF appear to be equally effective in controlling the symptoms of achalasia,shortening LOS, and minimizing AEs. Nevertheless, POEM has the advantage of improving all domains of QoL, and shortening anesthesia and procedure times but with a significantly higher rate of gastroesophageal reflux.

Mechanisms of tyrosine kinase inhibitor resistance in renal cell carcinoma

Renal cell carcinoma(RCC),the most prevalent type of kidney cancer,is a significant cause of cancer morbidity and mortality worldwide.Antiangiogenic tyrosine kinase inhibitors(TKls),in combination with immune checkpoint inhibitors(ICls),are among the first-line treatment options for patients with advanced RCC.These therapies target the vascular endothelial growth factor receptor(VEGFR)tyrosine kinase pathway and other kinases crucial to cancer proliferation,survival,and metastasis.TKls have yielded substantial improvements in progression-free survival(PFS)and overall survival(OS)for patients with advanced RCC.However,nearly all patients eventually progress on these drugs as resistance develops.This review provides an overview of TKl resistance in RCC and explores different mechanisms of resistance,including upregulation of alternative proangiogenic pathways,epithelial-mesenchymal transition(EMT),decreased intracellular drug concentrations due to efflux pumps and lysosomal sequestration,alterations in the tumor microenvironment including bone marrow-derived cells(BMDCs)and tumor-associated fibroblasts(TAFs),and genetic factors such as single nucleotide polymorphisms(SNPs).A comprehensive understanding of these mechanisms opens the door to the development of innovative therapeutic approaches that can effectively overcome TKl resistance,thereby improving outcomes for patients with advanced RCC.

An update on clinical trials for chemoprevention of human skin cancer

The pathophysiology of skin cancer is complex,with multiple factors contributing to its development.The proactive treatment of skin cancer has been investigated in the form of chemoprevention of cutaneous malignancies in clinical trials.Chemoprevention is the use of natural or pharmacologic agents that prevent or reverse skin cancer development.Multiple trials have arisen over the past decades to explore the efficacy of specific agents to halt the progression of UV radiation damage.This comprehensive review article aims to assess clinical trials performed with chemopreventive agents for melanoma and nonmelanoma skin cancers.The following compounds were most often used in these trials:nicotinamide,retinoids,polyphenolic antioxidants,COX-2 selective inhibitors,non-steroidal anti-inflammatory drugs,difluoromethylornithine,and 5-fluorouracil.Many agents show promise in their ability to prevent nonmelanoma skin cancer formation,with few melanoma trials demonstrating efficacy.The chemoprevention efforts aimed at skin cancer are complex;current and future trials will be instrumental in identifying therapeutic agents that pose efficacy in halting cancer development and assessing whether long-term administration is tolerable.

The BET inhibitor sensitivity is associated with the expression level of CDC25B in pancreatic cancer models

Aim:Cell division cycle 25B(CDC25B)belongs to the CDC25 family of phosphatases that regulate cell cycle progression.CDC25B also contributes to tumor initiation and progression,but no connection between CDC25B levels and drug sensitivity in pancreatic cancer has been reported.Based on our finding that bromodomain and extraterminal domain(BET)inhibitors decrease levels of CDC25B,we aim to compare the sensitivity of models expressing contrasting levels of CDC25B to the BET inhibitor JQ1,in pancreatic cancer cell lines in vitro and in patient-derived xenograft(PDX)models of pancreatic ductal adenocarcinoma(PDAC)in vivo.Methods:We compared the efficacy of the standard of care agent gemcitabine with the BET inhibitor JQ1,using alamarBlue assays to determine IC50s of three pancreatic cancer cell lines in vitro.We used immunohistochemistry(IHC)and immunoblot(IB)to detect CDC25B.We also compared the effect of each agent on the progression of PDX models of PDAC in vivo with contrasting levels of CDC25B.Results:Immunohistochemical data demonstrated that levels of CDC25B differed by~2-to 5-fold in cell lines and PDX models used.In vitro data showed that the level of CDC25B paralleled sensitivity to JQ1.Similarly,in vivo data showed that tumors with high-level CDC25B were more sensitive to JQ1 than tumors with lower CDC25B.The combination of JQ1+a pan CDC25 inhibitor was synergistic in gemcitabine-resistant Panc1.gemR cells that had relatively high levels of CDC25B expression compared to parent cells. Conclusion: The data suggest that CDC25B may be an independent indicator of sensitivity to BET inhibitors and that CDC25B may contribute to gemcitabine insensitivity in this tumor type.

Negotiating a new chair package:context and considerations

Negotiating a resource package as a potential new department chair is common practice in academic medicine.The foundations for this negotiation include the historical presence of the department in relation to the broader institution,projections for future growth,accounting for mission/vision,resource needs(space,personnel,finances,etc),faculty and staff development,and external partnerships within and outside the institution.Despite similarities in this process across departments,many nuances influence the development of a specific new chair package,such as,department size;desires,perspectives and talents of the incoming chair,the department faculty,the medical school and dean;prevailing agendas and mission imperatives;and the overall priorities of the institution.With strategy and forethought,a new chair package can promote a successful chair tenure and departmental growth.Assembled through the Association of Departments of Family Medicine with input from several dozen department chairs and senior leaders,this is intended to serve as a practical guide to new chair packages for chair candidates.