Factors influencing survival in sphingosine phosphate lyase insufficiency syndrome: a retrospective cross-sectional natural history study of 76 patients.

BACKGROUND: Sphingosine-1-phosphate lyase insufficiency syndrome (SPLIS) is a recently recognized inborn error of metabolism associated with steroid-resistant nephrotic syndrome as well as adrenal insufficiency and immunological, neurological, and skin manifestations. SPLIS is caused by inactivating mutations in SGPL1, encoding the pyridoxal 5'phosphate-dependent enzyme sphingosine-1-phosphate lyase, which catalyzes the final step of sphingolipid metabolism. Some SPLIS patients have undergone kidney transplantation, and others have been treated with vitamin B6 supplementation. In addition, targeted therapies including gene therapy are in preclinical development. In anticipation of clinical trials, it will be essential to characterize the full spectrum and natural history of SPLIS. We performed a retrospective analysis of 76 patients in whom the diagnosis of SPLIS was established in a proband with at least one suggestive finding and biallelic SGPL1 variants identified by molecular genetic testing. The main objective of the study was to identify factors influencing survival in SPLIS subjects. RESULTS: Overall survival at last report was 50%. Major influences on survival included: (1) age and organ involvement at first presentation; (2) receiving a kidney transplant, and (3) SGPL1 genotype. Among 48 SPLIS patients with nephropathy who had not received a kidney transplant, two clinical subgroups were distinguished. Of children diagnosed with SPLIS nephropathy before age one (n = 30), less than 30% were alive 2 years after diagnosis, and 17% were living at last report. Among those diagnosed at or after age one (n = 18), ~ 70% were alive 2 years after diagnosis, and 72% were living at time of last report. SPLIS patients homozygous for the SPL R222Q variant survived longer compared to patients with other genotypes. Kidney transplantation significantly extended survival outcomes. CONCLUSION: Our results demonstrate that SPLIS is a phenotypically heterogeneous condition. We find that patients diagnosed with SPLIS nephropathy in the first year of life and patients presenting with prenatal findings represent two high-risk subgroups, whereas patients harboring the R222Q SGPL1 variant fare better than the rest. Time to progression from onset of proteinuria to end stage kidney disease varies from less than one month to five years, and kidney transplantation may be lifesaving.

Salivary CD44 and Total Protein Levels to Detect Risk for Oral and Oropharyngeal Cancer Recurrence: A Nonrandomized Clinical Trial.

Importance: Oral and oropharyngeal cancer have low survival rates, and incidence continues to increase. Objective: To determine whether soluble CD44 and total protein (TP) are useful for monitoring head and neck cancer recurrence, either used in a point-of-care (POC) test or as individual laboratory-based biomarkers. Design, Setting, and Participants: This multi-institutional nonrandomized clinical trial testing a novel diagnostic/screening assay took place across the University of California, San Diego; Johns Hopkins University; the Greater Baltimore Medical Center; New York University; and the San Diego Veterans Affairs Hospital. Patients with newly biopsy-proven, untreated oral cavity and oropharyngeal cancer were enrolled. Patients were enrolled April 2017 to April 2019, and data were analyzed December 2022 to June 2023. Exposure: POC salivary oral rinse test. Main Outcomes and Measures: Oral rinses were collected at pretreatment baseline and 3, 6, 12, and 18 months after completion of therapy; participants were then followed up for 3 years to define disease status. Associations of baseline characteristics with a positive test were evaluated by Fisher exact test. The association of a positive value on the CD44 or TP test with progression-free survival was evaluated in an adjusted multivariable proportional hazards model. Results: Of 172 patients enrolled, the mean (SD) age was 62.5 (10.2) years, and 122 (70.9%) identified as male. Additionally, 92 patients (53.3%) had never smoked, 99 (57.6%) formerly or currently drank alcohol, and 113 (65.7%) presented with oropharyngeal cancers, which were positive for human papillomavirus in 95 (84.1%). Tumor site was associated with test results at baseline; patients with oral cavity cancer had a higher baseline positive POC test rate (47 of 51 [92.2%]) compared to patients with oropharyngeal cancer (85 of 110 [77.3%]). Using Cox regression models with CD44 or TP level as a time-varying covariate, a higher CD44 level showed a statistically significant association with a higher hazard of recurrence (hazard ratio, 1.06; 95% CI, 1.00-1.12), though the TP level was not statistically significant. In multivariate adjusted analysis, higher CD44 and TP levels were associated with increased hazard ratios of recurrence of 1.13 (95% CI, 1.04-1.22) and 3.51 (95% CI, 1.24-9.98), respectively. Conclusion and Relevance: In this multi-institutional nonrandomized clinical trial of an assay, posttreatment longitudinal monitoring for elevated salivary CD44 and TP levels using an enzyme-linked immunosorbent assay-based laboratory test identified patients at increased risk of future cancer recurrence. The CD44 and TP rapid POC test holds some promise, but further development is needed for this indication. Trial Registration: ClinicalTrials.gov Identifier: NCT03148665.

Helicobacter pylori infection does not influence the progression from gastroesophageal reflux disease to Barrett's esophagus to esophageal adenocarcinoma.

INTRODUCTION: We conducted a meta-analysis evaluating the overall risk of esophageal adenocarcinoma (EAC) in individuals with Helicobacter pylori infection, and a network meta-analysis to assess the role of H. pylori infection in the progression from Barrett's esophagus (BE) to EAC. EVIDENCE ACQUISITION: The MEDLINE, EMBASE and Cochrane databases were searched between 1988 and June 2023 for observational studies of H. pylori infection and the risk of EAC. Summary odds ratios (OR) and 95% confidence intervals (95% CI) were calculated using the DerSimonian-Laird method. I2 statistics were calculated to examine heterogeneity. EVIDENCE SYNTHESIS: Thirteen studies were included in the meta-analysis and 3 additional studies were included in the network meta-analysis. For comparisons with controls, individuals with H. pylori infection were 46% less likely to develop EAC than individuals without H. pylori infection (OR, 0.54; 95% CI: 0.46, 0.64), with low heterogeneity between studies (I2=4.4%). The magnitude of the inverse association was stronger in the two large cohort studies (OR=0.31) than in the 11 case-control studies (OR=0.55). When comparing to controls, the network meta-analysis of 6 studies showed that H. pylori infection was associated with a lower risk of GERD (OR=0.68) or BE (OR=0.59) or EAC (OR=0.54); however, H. pylori infection was not associated with risk of EAC in patients with BE (OR=0.91; 95% CI: 0.68, 1.21). CONCLUSIONS: This meta-analysis provides the strongest evidence yet that H. pylori infection is inversely associated with EAC. H. pylori does not appear to be associated with BE progression to EAC.

Preventive Saline Irrigation of the Bile Duct to Reduce the Rate of Residual Common Bile Duct Stones Without Intraductal Ultrasonography: A Systematic Review and Meta-Analysis.

Endoscopic retrograde cholangiopancreatography (ERCP) with endoscopic sphincterotomy (EST) has been proven efficacious in the removal of CBD stones. Even after endoscopic stone removal, recurring cholangitis due to a residual common bile duct (CBD) stone is prevalent in clinical practice with a residual recurrence rate of 4-24% after successful stone retrieval. This comprehensive study and meta-analysis aimed to determine if preventive saline irrigation of the bile duct (PSIB) reduces the amount of residual CBD stones. Through a comprehensive search of PubMed, EMBASE, Cochrane Library, and Web of Science until November 20, 2022, we identified 164 articles comparing the efficacy of PSIB and non-PSIB post-endoscopic CBD stone removal. After stringent selection, three studies were included for meta-analysis using ReviewManager (ReVman version 5.4.1; Cochrane, London, UK). Using a random effect (RE) model, we derived a pooled odds ratio (OR) with confidence interval (CI) (95%CI). A total of three studies have been included in the analysis. Out of which, two are randomized controlled trials (RCTs) and one is a non-randomized study. Out of 323 patients, 157 underwent PSIB after an endoscopic stone removal of CBD stones to reduce the residual of CBD stones, whereas 166 did not undergo saline irrigation (non-PSIB). In our analysis, PSIB significantly reduced the risk of residual stones (OR: 0.22, 95%CI: 0.11-0.45). However, there was no notable link between PSIB and post-irrigation cholangitis (OR: 1.08, 95%CI: 0.21-2.21). Although not statistically significant, PSIB showed a trend toward lowered risks of post-procedural pancreatitis (OR: 0.65), bleeding (OR: 0.68), and other complications (OR: 0.64). PSIB effectively reduces residual CBD stones after endoscopy, offering a cost-effective alternative to invasive procedures such as intraductal ultrasound (IDUS). However, larger RCTs are needed to validate its definitive role.

A Network Landscape of HPVOPC Reveals Methylation Alterations as Significant Drivers of Gene Expression via an Immune-Mediated GPCR Signal.

HPV-associated oropharynx carcinoma (HPVOPC) tumors have a relatively low mutational burden. Elucidating the relative contributions of other tumor alterations, such as DNA methylation alterations, alternative splicing events (ASE), and copy number variation (CNV), could provide a deeper understanding of carcinogenesis drivers in this disease. We applied network propagation analysis to multiple classes of tumor alterations in a discovery cohort of 46 primary HPVOPC tumors and 25 cancer-unaffected controls and validated our findings with TCGA data. We identified significant overlap between differential gene expression networks and all alteration classes, and this association was highest for methylation and lowest for CNV. Significant overlap was seen for gene clusters of G protein-coupled receptor (GPCR) pathways. HPV16-human protein interaction analysis identified an enriched cluster defined by an immune-mediated GPCR signal, including CXCR3 cytokines CXCL9, CXCL10, and CXCL11. CXCR3 was found to be expressed in primary HPVOPC, and scRNA-seq analysis demonstrated CXCR3 ligands to be highly expressed in M2 macrophages. In vivo models demonstrated decreased tumor growth with antagonism of the CXCR3 receptor in immunodeficient but not immunocompetent mice, suggesting that the CXCR3 axis can drive tumor proliferation in an autocrine fashion, but the effect is tempered by an intact immune system. In conclusion, methylation, ASE, and SNV alterations are highly associated with network gene expression changes in HPVOPC, suggesting that ASE and methylation alterations have an important role in driving the oncogenic phenotype. Network analysis identifies GPCR networks, specifically the CXCR3 chemokine axis, as modulators of tumor-immune interactions that may have proliferative effects on primary tumors as well as a role for immunosurveillance; however, CXCR3 inhibition should be used with caution, as these agents may both inhibit and stimulate tumor growth considering the competing effects of this cytokine axis. Further investigation is needed to explore opportunities for targeted therapy in this setting.

Distal positioning of the skin paddle of pectoralis major myocutaneous flap in head and neck reconstruction.

BACKGROUND: To assess outcomes of pectoralis major myocutaneous flap (PMF) wherein the skin paddle (SP) was positioned with its distal portion extending beyond the lower border of pectoralis major by ≥2 cm (PMF-d). METHODS: Consecutive head and neck reconstructions with PMF-d (n = 110). SP dimensions l2 (distal extent below the lower border of pectoralis major), l1 (proximal extent above lower border of pectoralis major), and b (breadth) were recorded. Endpoints were SP necrosis, recipient dehiscence, early fistula, and persistent fistula. RESULTS: Median values of l2 , l1 , and b were 3.0, 6.0, and 6.0 cm, respectively. When l2 = 2.0-3.0 cm, SP necrosis occurred in only one (1%) subject (with obesity). When l2 was ≥3.5 cm, necrosis occurred in four (16%) subjects, three of whom also had l1 /l2 < 2.0 (proximal SP < 67% of entire SP). Statistically, increased l2 was the only risk factor for necrosis (p = 0.001). Overall, incidence of recipient dehiscence, early fistula, and persistent fistula were 32 (29%), 20 (20%), and 3 (3%), respectively. Persistent fistula occurred only in the setting of SP necrosis and/or re-irradiation. CONCLUSION: Careful patient selection, adequate proximal SP, and l2 = 2.0-3.0 cm is associated with a negligible risk of necrosis. The enhanced reach and laxity and additional skin surface area and soft tissue volume conferred with PMF-d facilitate recipient wound healing.

Nyctalopia and Xerophthalmia in a Patient With Crohn's Induced Vitamin A Deficiency.

The vitamin A derivative, retinal, plays a pivotal role in scotopic and color vision. Although vitamin A deficiency (VAD) presents as a common cause of preventable blindness in areas with poor access to foods rich in vitamin A, it is uncommon in developed countries. We present a 56-year-old male with a history of Crohn's disease and pancreatitis who was referred to our ophthalmology office by optometry for severe dry eyes. He complained of a two-year history of constant blurred vision and nyctalopia. He stated that "images just appear dark." Examination demonstrated mildly decreased visual acuity with severe ocular surface disease and characteristic Bitot's spots in both eyes. Based on the patient's history and physical, a diagnosis of xerophthalmia in the setting of VAD was made. The patient was referred to his internist, he then underwent further evaluation and treatment with vitamin A intramuscular injections post-diagnosis.  This case illustrates the potential for VAD secondary to malabsorption from Crohn's disease and the importance of taking a full patient history so systemic causes of ophthalmic symptoms may be promptly identified and treated. VAD is extremely rare in the United States, however, patients at risk for VAD may benefit from regular vitamin A level checks and ophthalmologic evaluation.

Study protocol: randomised controlled trial of conditioned open-label placebo (COLP) for perioperative pain management in patients with head and neck cancer.

INTRODUCTION: Patients with head and neck cancer have a substantial risk of chronic opioid dependence following surgery due to pain and psychosocial consequences from both the disease process and its treatments. Conditioned open-label placebos (COLPs) have been effective for reducing the dose of active medication required for a clinical response across a wide range of medical conditions. We hypothesise that the addition of COLPs to standard multimodal analgesia will be associated with reduced baseline opioid consumption by 5 days after surgery in comparison to standard multimodal analgesia alone in patients with head and neck cancer. METHODS AND ANALYSIS: This randomised controlled trial will evaluate the use of COLP for adjunctive pain management in patients with head and neck cancer. Participants will be randomised with 1:1 allocation to either the treatment as usual or COLP group. All participants will receive standard multimodal analgesia, including opioids. The COLP group will additionally receive conditioning (ie, exposure to a clove oil scent) paired with active and placebo opioids for 5 days. Participants will complete surveys on pain, opioid consumption and depression symptoms through 6 months after surgery. Average change in baseline opioid consumption by postoperative day 5 and average pain levels and opioid consumption through 6 months will be compared between groups. ETHICS AND DISSEMINATION: There remains a demand for more effective and safer strategies for postoperative pain management in patients with head and neck cancer as chronic opioid dependence has been associated with decreased survival in this patient population. Results from this study may lay the groundwork for further investigation of COLPs as a strategy for adjunctive pain management in patients with head and neck cancer. This clinical trial has been approved by the Johns Hopkins University Institutional Review Board (IRB00276225) and is registered on the National Institutes of Health Clinical Trials Database. TRIAL REGISTRATION NUMBER: NCT04973748.

Continuing Medical Education Questions: May 2023.

Article Title: Linaclotide Reduced Response Time for Irritable Bowel Syndrome with Constipation Symptoms: Analysis of Four Randomized Controlled Trials.

Impact of Risk Factors and Long Term Survival Analysis of Patients With Primary Refractory Hodgkin Lymphoma Who Underwent High Dose Chemotherapy and Autologous Stem Cell Transplant.

Patients with primary refractory Hodgkin lymphoma (ref-HL) can still be salvaged with high-dose chemotherapy (HDC) and autologous stem cell transplantation (auto-SCT). Outcomes of patients with ref-HL is poorer than those with relapsed HL, but most studies have included patients with both relapsed and refractory diseases, and separate analyses or studies on patients with ref-HL are limited. This study aimed to evaluate the outcomes of HDC auto-SCT and impact of various prognostic factors in patients with ref-HL at the time of primary treatment failure and subsequent survival at the time of failure post-HDC auto-SCT. This retrospective single-institution cohort analysis using an HDC and auto-SCT database was approved by the Institutional Research Advisory Counsel and Ethics Committee for identifying patients. We used the Fine and Gray competing risk analysis method, a regression model for outcome analysis, and the Kaplan-Meier (KM) method for survival analysis. The study cohort comprised 200 consecutive ref-HL patients who underwent HDC auto-SCT between 1996 and 2019. The median patient age was 22.75 years, and median follow-up was 106 months. Post-auto-SCT disease status was complete remission (CR) in 122 patients (61%), partial remission in 22 (11%), and progressive disease in 47 (23.5%). KM median progression-free survival (PFS) after auto-SCT was 43.9 months (5 years, 49.3%; 10 years, 45.5%). Median overall survival (OS) was 168.6 months (5 years, 61.2%: 10 years, 56.2%). Eighty-five patients (44.5%) died, 69 (34.5%) due to disease. Multivariate analysis identified similar adverse factors for both PFS and OS. For PFS, these adverse factors included stage III-IV at relapse (hazard ratio [HR], 1.65; P = .045), mediastinal involvement (HR, 2.01; P = .009), and absence of CR after salvage chemotherapy (HR, 2.2; P = .001). PFS with 0 or 1 adverse factors (not reached), 2 adverse factors (40.8 months), and 3 adverse factors (5.4 months) was significant (P < .001). For OS, significant adverse factors included stage III-IV at relapse (HR, 1.68; P = .045), mediastinal involvement (HR, 2.52; P = .007), and no CR after salvage chemotherapy (HR, 2.15; P = .004) were significant. OS with 0 or 1 adverse factors (not reached), 2 adverse factors (148.5 months), and 3 adverse factors (34.4 months) was significant (P < .001). The median OS after auto-SCT failure was 23.6 months; patients received post auto-SCT brentuximab/second SCT (not reached), other treatments (22.5 months), and supportive care (8.4 months) (P < .001). OS with 5 risk factors present at HDC auto-SCT failure- stage III-IV, failure at <12 months, tumor >5 cm, B symptoms, and low serum albumin-was 152 months for 0 or 1 risk factors, 30.9 months with 2 risk factors, and 9.45 months with 3 to 5 risk factors (P < .001). Ref-HL patients have encouraging survival after HDC auto-SCT and can even be salvaged after auto-SCT failure. Based on prognostic factors, survival prediction is possible. Patients who fail to respond to HDC auto-SCT may benefit from newer treatments strategies and may qualify for enrollment in clinical trials.

Assessing Correlation Between Thoracic Impedance and Remotely Monitored Pulmonary Artery Pressure in Chronic Systolic Heart Failure.

Background: Heart failure (HF) readmission continues to be a major health problem. Monitoring pulmonary artery pressure (PAP) and thoracic impedance (TI) are the two modalities utilized for early identification of decompensation in HF patients. We aimed to assess the correlation between these two modalities in patients who simultaneously had both the devices. Methods: Patients with history of New York Heart Association class III systolic HF with a pre-implanted intracardiac defibrillator (ICD) capable of monitoring TI and pre-implanted CardioMEMs™ remote HF monitoring device were included. Hemodynamic data including TI and PAPs were measured at baseline and then weekly. Weekly percentage change was then calculated as: Weekly percentage change = (week 2 - week1)/week 1 × 100. Variability between the methods was expressed by Bland-Altman analysis. Significance was determined as a P-value < 0.05. Results: Nine patients met the inclusion criteria. There was no significant correlation between the assessed weekly percentage changes in pulmonary artery diastolic pressure (PAdP) and TI measurements (r = -0.180, P = 0.065). Using Bland-Altman analytic methods, both methods had no significant difference in agreement (0.011±0.094%, P = 0.215). With the linear regression model applied for Bland-Altman analysis, the two methods appeared to have proportional bias without agreement (unstandardized beta-coefficient of 1.91, t 22.9, P ≤ 0.001). Conclusion: Our study demonstrated that variations exist between measurement of PAdP and TI; however, there is no significant correlation between weekly variations between them.

Mesenchymal stem cell therapy for treatment of osteoradionecrosis of mandible in head and neck surgery patients - A way forward into the future with promising clinical Outcomes.

Managing osteoradionecrosis is an integral part of complication management in head and neck cancer patients. While essentially an infection, the management of this complication has a considerable task for head and neck surgeons. While various measures have been discussed for the management, stem cells injection therapy is a potential management option. Mesenchymal stem cell therapy provides the local tissue with growth factors and proliferative cells that can aid a radiated tissue in the healing process. The article intends to review the bedrock of the pathology, ranging from pathophysiological and the epidemiological concerns to sparking a potential discussion on the use of mesenchymal stem cell therapy in osteoradionecrosis of mandible in head and neck cancer surgery and thus the ensuing future of the regenerative medicine. Moreover, the article has considered the management option in a developing nation thus explaining the procedural as well as the financial pitfalls and has highlighted the potential loop holes to be addressed in the management of osteoradionecrosis with stem cell therapy.

Short-term outcomes after peroral endoscopic myotomy, Heller myotomy, and pneumatic dilation in patients with achalasia: a nationwide analysis.

BACKGROUND AND AIMS: Peroral endoscopic myotomy (POEM), laparoscopic Heller myotomy (LHM), and pneumatic dilation (PD) are the most common modalities for management of achalasia. Our study aimed to directly compare their short-term outcomes and safety profile in a hospitalized cohort in the United States. METHODS: The National Readmission Database (2016-2019) was queried using International Classification of Diseases, Tenth Revision, Clinical Modification codes to identify a cohort of inpatient admissions who underwent POEM, LHM, or PD. Baseline demographic variables, resource utilization, periprocedural outcomes, and 30-day readmissions were analyzed. A univariate and multivariate logistic regression model was used to compare odds of readmission with POEM as a reference. RESULTS: LHM was the most performed procedure (n = 9710) as compared with PD (n = 2453) and POEM (n = 1911). Patients undergoing PD were older with a higher Charlson Comorbidity Index. The 30-day readmission rate was 4.3%, 3.9%, and 12.6% for POEM, LHM, and PD, respectively. Compared with POEM, the adjusted odds of readmission for PD was 2.42 (95% confidence interval, 1.56-3.75). There was no statistically significant difference in odds of readmission for LHM (.91; 95% confidence interval, .62-1.33) compared with POEM. Within the 30-day readmitted population, 13.1% of PD and 3.4% of LHM patients required achalasia-related procedural intervention. The rate of bleeding (4.3%), blood transfusion (2.3%), and mortality were higher (1.1%) in PD as compared with POEM and LHM. CONCLUSIONS: In the United States, the risk of readmission and resource utilization are higher in patients with achalasia undergoing PD. The outcomes are comparable between POEM and LHM, but there is a significant difference between the utilization of these myotomy procedures.

Is antibiotic prophylaxis necessary after endoscopic ultrasound-guided fine-needle aspiration of pancreatic cysts?

BACKGROUND/AIMS: Current society guidelines recommend antibiotic prophylaxis for 3 to 5 days after endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) of pancreatic cystic lesions (PCLs). The overall quality of the evidence supporting this recommendation is low. In this study, we aimed to assess cyst infection and adverse event rates after EUS-FNA of PCLs among patients treated with or without postprocedural prophylactic antibiotics. METHODS: We retrospectively reviewed all patients who underwent EUS-FNA of PCLs between 2015 and 2019 at two large-volume academic medical centers with different practice patterns of postprocedural antibiotic prophylaxis. Data on patient demographics, cyst characteristics, fine-needle aspiration technique, periprocedural and postprocedural antibiotic prophylaxis, and adverse events were retrospectively extracted. RESULTS: A total of 470 EUS-FNA procedures were performed by experienced endosonographers for the evaluation of PCLs in 448 patients, 58.7% of whom were women. The mean age was 66.3±12.8 years. The mean cyst size was 25.7±16.9 mm. Postprocedural antibiotics were administered in 274 cases (POSTAB+ group, 58.3%) but not in 196 cases (POSTAB- group, 41.7%). None of the patients in either group developed systemic or localized infection within the 30-day follow-up period. Procedure-related adverse events included mild abdominal pain (8 patients), intra-abdominal hematoma (1 patient), mild pancreatitis (1 patient), and perforation (1 patient). One additional case of pancreatitis was recorded; however, the patient also underwent endoscopic retrograde cholangiopancreatography. CONCLUSION: The incidence of infection after EUS-FNA of PCLs is negligible. Routine use of postprocedural antibiotics does not add a significant benefit.

The Standard Operating Procedures in COVID-19 Pandemic for Periodontal Aerosol-Generating Procedures: A Process Audit.

OBJECTIVE: This study aims to audit the process of patient management with aerosol-generating procedure (ultrasonic scaling) while adherence to the guidelines for health care workers (HCWs) during the coronavirus disease 2019 (COVID-19). MATERIALS AND METHODS: Audits records at the Department of Periodontology at University College of Medicine and Dentistry Hospital, Lahore, Pakistan were collected (prospectively) over the period of October 1 to November 30, 2020 (1st cycle) and December 14, 2020 to February 12, 2021 (2nd cycle). The audit was divided into three components based on the guidelines: (1) physical environment, (2) patients/appointments, and (3) COVID standard operating procedures related to HCWs. RESULTS: The recommended physical layout and procedural factors, as suggested by the guidelines for dental clinics, were observed during the first cycle of audit, and discrepancy of ventilation system was fixed after the first cycle. Audit team reported the observance of fallow time three times daily, which revealed 83.3% observance of fallow time.Later in the second cycle when the extraoral high-volume air evacuator was installed, the fallow time was reduced to 15 minutes and not only five procedural slots per day were created but fallow time was also observed 100% of the time. CONCLUSION: Following the standard guidelines resulted in more efficient working environment and lesser risk for HCWs while performing aerosol-generating procedures.

Endoscopic sphincterotomy vs papillary large balloon dilation vs combination modalities for large common bile duct stones: a network meta-analysis.

Background and study aims The optimal technique for removal of large common bile duct (CBD) stones (≥ 10 mm) during endoscopic retrograde cholangiopancreatography (ERCP) remains unclear. We aimed to perform a comparative analysis between different endoscopic techniques. Methods Adhering to PRISMA guidelines, a stringent search of the following databases through January 12, 2021, were undertaken: PubMed/Medline, Embase, Web of Science, and Cochrane. Randomized controlled trials comparing the following endoscopic techniques were included: (1) Endoscopic sphincterotomy (EST); (2) Endoscopic papillary large balloon dilation (EPLBD); and (3) EST plus large balloon dilation (ESLBD). Stone clearance rate (SCR) on index ERCP was the primary outcome/endpoint. Need for mechanical lithotripsy (ML) and adverse events were also evaluated as secondary endpoint. Random effects model and frequentist approach were used for statistical analysis. Results A total of 16 studies with 2545 patients (1009 in EST group, 588 in EPLBD group, and 948 patients in ESLBD group) were included. The SCR was significantly higher in ESLBD compared to EST risk ratio [RR]: 1.11, [confidence interval] CI: 1.00-1.24). Lower need for ML was noted for ESLBD (RR: 0.48, CI: 0.31-0.74) and EPLBD (RR: 0.58, CI: 0.34-0.98) compared to EST. All other outcomes including bleeding, perforation, post-ERCP pancreatitis, stone recurrence, cholecystitis, cholangitis, and mortality did not show significant difference between the three groups. Based on network ranking, ESLBD was superior in terms of SCR as well as lower need for ML and adverse events (AEs). Conclusions Based on network meta-analysis, ESLBD seems to be superior with higher SCR and lower need for ML and AEs for large CBD stones.

Inter-Electronic Interaction between Ni and Mo in Electrodeposited Ni-Mo-P on 3D Copper Foam Enables Hydrogen Evolution Reaction at Low Overpotential.

Electrocatalytic hydrogen evolution reaction (HER) via water electrolysis has been considered the most effective and sustainable route to produce clean hydrogen. Designing and structure optimization are the two important parameters to develop an affordable, easy to fabricate, and stable non-noble metal electrocatalyst for the production of hydrogen as a clean, sustainable, and green fuel. Herein, we have synthesized Ni-Mo-P on copper foam (Cuf) via a facile single-step electrodeposition method, which can show stratospheric efficiency toward HER with a Tafel slope of 67 mV dec-1 and a very low overpotential of only 53 mV at a current density of 20 mA cm-2. Cuf acts as a conducting substrate support and the existence of the inter-electronic effect between Ni and Mo results in substantial catalytic activity toward hydrogen generation. In addition to this, the catalyst shows long time stability of around 97.5 h with almost negligible degradation under the applied overpotential for HER in alkaline media. This work features the significance of structure design and construction of non-noble metal catalysts via a simple method for efficient hydrogen generation.

Tuning the Electronic Structure of Cobalt Selenide on Copper Foam by Introducing a Ni Buffer Layer for Highly Efficient Electrochemical Water Splitting.

The development of a cost-effective, remarkably competent, and durable bifunctional electrocatalyst is the foremost requirement of water splitting to generate H2 fuel as a renewable energy technology. Three-dimensional porous copper foam (Cuf) when electrochemically decorated with transition metal selenide results in a highly active electrocatalyst for adequate water electrolysis. In terms of water splitting, the role of cobalt selenide and Cuf has already proven to be remarkable. The introduction of a Ni buffer layer between Cuf and cobalt selenide (Cuf@Ni-CoSe2) acts as a valve to enhance the electron thrust from the substrate to the material surface with no compromise in the overall material conductivity, which not only increases the efficiency and activity but also improves the stability of the catalyst. The self-supported synthesized catalyst material showed an admirable activity toward the oxygen evolution reaction and hydrogen evolution reaction in alkaline media. The performance of the catalyst was found to be significantly better than that of the noble catalyst RuO2. The catalyst was very stable up to 93 h and attained a full cell voltage of only 1.52 V at a current density of 10 mA cm-2. Therefore, for large-scale hydrogen production, this as-synthesized catalyst hss the potential to replace conventional fossil fuel-based energy systems.