Identification and structural characterization of a pathogenic ARSA missense variant in two consanguineous families from Jammu and Kashmir (India) with late infantile metachromatic leukodystrophy.

BACKGROUND: Metachromatic leukodystrophy (MLD) is a rare lysosomal storage disorder caused by a deficiency of Arylsulfatase A (ARSA) enzyme activity. Its clinical manifestations include progressive motor and cognitive decline. ARSA gene mutations are frequent in MLD. METHODS AND RESULTS: In the present study, whole exome sequencing (WES) was employed to decipher the genetic cause of motor and cognitive decline in proband's of two consanguineous families from J&K (India). Clinical investigations using radiological and biochemical analysis revealed MLD-like features. WES confirmed a pathogenic variant in the ARSA gene. Molecular simulation dynamics was applied for structural characterization of the variant. CONCLUSION: We report the identification of a pathogenic missense variant (c.1174 C > T; p.Arg390Trp) in the ARSA gene in two cases of late infantile MLD from consanguineous families in Jammu and Kashmir, India. Our study utilized genetic analysis and molecular dynamics simulations to identify and investigate the structural consequences of this mutation. The molecular dynamics simulations revealed significant alterations in the structural dynamics, residue interactions, and stability of the ARSA protein harbouring the p.Arg390Trp mutation. These findings provide valuable insights into the molecular mechanisms underlying the pathogenicity of this variant in MLD.

Evaluation of Large-Scale Proteomics for Prediction of Cardiovascular Events.

Importance: Whether protein risk scores derived from a single plasma sample could be useful for risk assessment for atherosclerotic cardiovascular disease (ASCVD), in conjunction with clinical risk factors and polygenic risk scores, is uncertain. Objective: To develop protein risk scores for ASCVD risk prediction and compare them to clinical risk factors and polygenic risk scores in primary and secondary event populations. Design, Setting, and Participants: The primary analysis was a retrospective study of primary events among 13 540 individuals in Iceland (aged 40-75 years) with proteomics data and no history of major ASCVD events at recruitment (study duration, August 23, 2000 until October 26, 2006; follow-up through 2018). We also analyzed a secondary event population from a randomized, double-blind lipid-lowering clinical trial (2013-2016), consisting of individuals with stable ASCVD receiving statin therapy and for whom proteomic data were available for 6791 individuals. Exposures: Protein risk scores (based on 4963 plasma protein levels and developed in a training set in the primary event population); polygenic risk scores for coronary artery disease and stroke; and clinical risk factors that included age, sex, statin use, hypertension treatment, type 2 diabetes, body mass index, and smoking status at the time of plasma sampling. Main Outcomes and Measures: Outcomes were composites of myocardial infarction, stroke, and coronary heart disease death or cardiovascular death. Performance was evaluated using Cox survival models and measures of discrimination and reclassification that accounted for the competing risk of non-ASCVD death. Results: In the primary event population test set (4018 individuals [59.0% women]; 465 events; median follow-up, 15.8 years), the protein risk score had a hazard ratio (HR) of 1.93 per SD (95% CI, 1.75 to 2.13). Addition of protein risk score and polygenic risk scores significantly increased the C index when added to a clinical risk factor model (C index change, 0.022 [95% CI, 0.007 to 0.038]). Addition of the protein risk score alone to a clinical risk factor model also led to a significantly increased C index (difference, 0.014 [95% CI, 0.002 to 0.028]). Among White individuals in the secondary event population (6307 participants; 432 events; median follow-up, 2.2 years), the protein risk score had an HR of 1.62 per SD (95% CI, 1.48 to 1.79) and significantly increased C index when added to a clinical risk factor model (C index change, 0.026 [95% CI, 0.011 to 0.042]). The protein risk score was significantly associated with major adverse cardiovascular events among individuals of African and Asian ancestries in the secondary event population. Conclusions and Relevance: A protein risk score was significantly associated with ASCVD events in primary and secondary event populations. When added to clinical risk factors, the protein risk score and polygenic risk score both provided statistically significant but modest improvement in discrimination.

Goff Septotomy Is a Safe and Effective Salvage Biliary Access Technique Following Failed Cannulation at ERCP.

BACKGROUND: Biliary cannulation is readily achieved in > 85% of patients undergoing endoscopic retrograde cholangiopancreatography (ERCP). When standard cannulation techniques fail, salvage techniques utilized include the needle knife precut, double wire technique, and Goff septotomy. METHODS: Records of patients undergoing ERCP from 2005 to 2016 were retrospectively examined using a prospectively maintained endoscopy database. Patients requiring salvage techniques for biliary access were analyzed together with a control sample of 20 randomly selected index ERCPs per study year. Demographic and clinical variables including indications for ERCP, cannulation rates, and adverse events were collected. RESULTS: A total of 7984 patients underwent ERCP from 2005 to 2016. Biliary cannulation was successful in 94.9% of control index ERCPs, 87.2% of patients who underwent Goff septotomy (significantly higher than for all other salvage techniques, p ≤ 0.001), 74.5% of patients in the double wire group and 69.6% of patients in the needle knife precut group. Adverse event rates were similar in the Goff septotomy (4.1%) and index ERCP control sample (2.7%) groups. Adverse events were significantly higher in the needle knife group (27.2%) compared with all other groups. CONCLUSIONS: This study represents the largest study to date of Goff septotomy as a salvage biliary access technique. It confirms the efficacy of Goff septotomy and indicates a safety profile similar to standard cannulation techniques and superior to the widely employed needle knife precut sphincterotomy. Our safety and efficacy data suggest that Goff septotomy should be considered as the primary salvage approach for failed cannulation, with needle knife sphincterotomy restricted to Goff septotomy failures.

Association between maternal periodontal disease and adverse pregnancy outcomes: an analysis of claims data.

BACKGROUND: While a number of studies have explored the link between periodontal disease and adverse pregnancy outcomes, both epidemiological studies and intervention trials have reached contradictory results with relatively small sample sizes. Utilizing large-scale claims data, we aim to investigate the association between maternal periodontal disease and adverse pregnancy outcomes. OBJECTIVE: Utilizing large-scale claims data, we aim to investigate the association between maternal periodontal disease and adverse pregnancy outcomes. METHODS: Using de-identified claims data from a national commercial insurer in the USA, records of all observed pregnancies from 2015 to 2019 were included in this retrospective cohort study. Adverse pregnancy outcomes, including low birthweight (LBW) of the newborn, preterm birth (PTB) and spontaneous abortion, were primary outcomes. To evaluate the association between periodontal disease and pregnancy outcomes, logistic mixed-effect model was estimated with periodontal disease status, age, existing clinical conditions of mothers and geographic location as covariates. RESULTS: Out of 748 792 observed pregnancy records, 18.66% resulted in adverse pregnancy outcomes; 5.92% in LBW, 14.46% in PTB and 2.22 % in spontaneous abortion. Adjusting for individual-level risk factors, periodontal disease was significantly associated with maternal complications with odds ratios of 1.19 (95% CI:1.15, 1.24) for any adverse pregnancy outcomes, 1.10 (95% CI:1.03, 1.17) for LBW, 1.15 (95% CI:1.10, 1.19) for PTB and 1.34 (95% CI:1.23, 1.46) for spontaneous abortions. CONCLUSIONS: Maternal periodontal disease may be associated with an increased risk of maternal complications and neonatal morbidity. A timely diagnosis and treatment of periodontal disease during pregnancy should be encouraged by considering oral health as part of routine prenatal care.

The MAZ transcription factor is a downstream target of the oncoprotein Cyr61/CCN1 and promotes pancreatic cancer cell invasion via CRAF-ERK signaling.

Myc-associated zinc-finger protein (MAZ) is a transcription factor with dual roles in transcription initiation and termination. Deregulation of MAZ expression is associated with the progression of pancreatic ductal adenocarcinoma (PDAC). However, the mechanism of action of MAZ in PDAC progression is largely unknown. Here, we present evidence that MAZ mRNA expression and protein levels are increased in human PDAC cell lines, tissue samples, a subcutaneous tumor xenograft in a nude mouse model, and spontaneous cancer in the genetically engineered PDAC mouse model. We also found that MAZ is predominantly expressed in pancreatic cancer stem cells. Functional analysis indicated that MAZ depletion in PDAC cells inhibits invasive phenotypes such as the epithelial-to-mesenchymal transition, migration, invasion, and the sphere-forming ability of PDAC cells. Mechanistically, we detected no direct effects of MAZ on the expression of K-Ras mutants, but MAZ increased the activity of CRAF-ERK signaling, a downstream signaling target of K-Ras. The MAZ-induced activation of CRAF-ERK signaling was mediated via p21-activated protein kinase (PAK) and protein kinase B (AKT/PKB) signaling cascades and promoted PDAC cell invasiveness. Moreover, we found that the matricellular oncoprotein cysteine-rich angiogenic inducer 61 (Cyr61/CCN1) regulates MAZ expression via Notch-1-sonic hedgehog signaling in PDAC cells. We propose that Cyr61/CCN1-induced expression of MAZ promotes invasive phenotypes of PDAC cells not through direct K-Ras activation but instead through the activation of CRAF-ERK signaling. Collectively, these results highlight key molecular players in PDAC invasiveness and may help inform therapeutic strategies to improve clinical management and outcomes of PDAC.

Competence in Endoscopic Ultrasound and Endoscopic Retrograde Cholangiopancreatography, From Training Through Independent Practice.

BACKGROUND & AIMS: It is unclear whether participation in competency-based fellowship programs for endoscopic ultrasound (EUS) and endoscopic retrograde cholangiopancreatography (ERCP) results in high-quality care in independent practice. We measured quality indicator (QI) adherence during the first year of independent practice among physicians who completed endoscopic training with a systematic assessment of competence. METHODS: We performed a prospective multicenter cohort study of invited participants from 62 training programs. In phase 1, 24 advanced endoscopy trainees (AETs), from 20 programs, were assessed using a validated competence assessment tool. We used a comprehensive data collection and reporting system to create learning curves using cumulative sum analysis that were shared with AETs and trainers quarterly. In phase 2, participating AETs entered data into a database pertaining to every EUS and ERCP examination during their first year of independent practice, anchored by key QIs. RESULTS: By the end of training, most AETs had achieved overall technical competence (EUS 91.7%, ERCP 73.9%) and cognitive competence (EUS 91.7%, ERCP 94.1%). In phase 2 of the study, 22 AETs (91.6%) participated and completed a median of 136 EUS examinations per AET and 116 ERCP examinations per AET. Most AETs met the performance thresholds for QIs in EUS (including 94.4% diagnostic rate of adequate samples and 83.8% diagnostic yield of malignancy in pancreatic masses) and ERCP (94.9% overall cannulation rate). CONCLUSIONS: In this prospective multicenter study, we found that although competence cannot be confirmed for all AETs at the end of training, most meet QI thresholds for EUS and ERCP at the end of their first year of independent practice. This finding affirms the effectiveness of training programs. Clinicaltrials.gov ID NCT02509416.

Setting minimum standards for training in EUS and ERCP: results from a prospective multicenter study evaluating learning curves and competence among advanced endoscopy trainees.

BACKGROUND AND AIMS: Minimum EUS and ERCP volumes that should be offered per trainee in "high quality" advanced endoscopy training programs (AETPs) are not established. We aimed to define the number of procedures required by an "average" advanced endoscopy trainee (AET) to achieve competence in technical and cognitive EUS and ERCP tasks to help structure AETPs. METHODS: American Society for Gastrointestinal Endoscopy (ASGE)-recognized AETPs were invited to participate; AETs were graded on every fifth EUS and ERCP examination using a validated tool. Grading for each skill was done using a 4-point scoring system, and learning curves using cumulative sum analysis for overall, technical, and cognitive components of EUS and ERCP were shared with AETs and trainers quarterly. Generalized linear mixed-effects models with a random intercept for each AET were used to generate aggregate learning curves, allowing us to use data from all AETs to estimate the average learning experience for trainees. RESULTS: Among 62 invited AETPs, 37 AETs from 32 AETPs participated. Most AETs reported hands-on EUS (52%, median 20 cases) and ERCP (68%, median 50 cases) experience before starting an AETP. The median number of EUS and ERCPs performed per AET was 400 (range, 200-750) and 361 (range, 250-650), respectively. Overall, 2616 examinations were graded (EUS, 1277; ERCP-biliary, 1143; pancreatic, 196). Most graded EUS examinations were performed for pancreatobiliary indications (69.9%) and ERCP examinations for ASGE biliary grade of difficulty 1 (72.1%). The average AET achieved competence in core EUS and ERCP skills at approximately 225 and 250 cases, respectively. However, overall technical competence was achieved for grade 2 ERCP at about 300 cases. CONCLUSION: The thresholds provided for an average AET to achieve competence in EUS and ERCP may be used by the ASGE and AETPs in establishing the minimal standards for case volume exposure for AETs during their training. (Clinical trial registration number: NCT02509416.).

Effects of a Brief Educational Program on Optimization of Fluoroscopy to Minimize Radiation Exposure During Endoscopic Retrograde Cholangiopancreatography.

BACKGROUND & AIMS: Fluoroscopy during endoscopic retrograde cholangiopancreatography (ERCP) is increasingly performed by therapeutic endoscopists, many of whom have not received formal training in modulating fluoroscopy use to minimize radiation exposure. Exposure to ionizing radiation has significant health consequences for patients and endoscopists. We aimed to evaluate whether a 20-minute educational intervention for endoscopists would improve use of fluoroscopy and decrease ERCP-associated exposure to radiation for patients. METHODS: We collected data from 583 ERCPs, performed in California from June 2010 through November 2012; 331 were performed at baseline and 252 following endoscopist education. The educational intervention comprised a 20-minute video explaining best practices for fluoroscopy, coupled with implementation of a formal fluoroscopy time-out protocol before the ERCP was performed. Our primary outcome was the effect of the educational intervention on direct and surrogate markers of patient radiation exposure associated with ERCPs performed by high-volume endoscopists (HVEs) (200 or more ERCPs/year) vs low-volume endoscopists (LVEs) (fewer than 200 ERCPs/year). RESULTS: At baseline, total radiation dose and dose area product were significantly higher for LVEs, but there was no significant difference between HVEs and LVEs following education. Education was associated with significant reductions in median fluoroscopy time (48% reduction for HVEs vs 30% reduction for LVEs), total radiation dose (28% reduction for HVEs vs 52% for LVEs) and dose area product (35% reduction for HVEs vs 48% reduction for LVEs). All endoscopists significantly increased their use of low magnification and collimation following education. CONCLUSIONS: A 20-minute educational program with emphasis on ideal use of modifiable fluoroscopy machine settings results in an immediate and significant reduction in ERCP-associated patient radiation exposure for low-volume and high-volume endoscopists. Training programs should consider radiation education for advanced endoscopy fellows.

A prospective evaluation of radiation-free direct solitary cholangioscopy for the management of choledocholithiasis.

BACKGROUND AND AIMS: Endoscopy has replaced many radiologic studies for the GI tract. However, ERCP remains a hybrid endoscopic-fluoroscopic procedure, which limits its portable delivery, creates delays because of fluoroscopy room unavailability, and exposes patients and providers to radiation. We evaluated fluoroscopy/radiation-free management of patients with noncomplex choledocholithiasis using direct solitary cholangioscopy (DSC). METHODS: Patients underwent fluoroscopy-free biliary cannulation, sphincterotomy, and then cholangioscopy to establish location and number/size of stones and to document distance from ampulla to bifurcation to guide balloon advancement. Stones were extracted using a marked balloon catheter advanced to the bifurcation and inflated to the bile duct diameter, documented on prior imaging. Repeat cholangioscopy was performed to confirm stone clearance. RESULTS: Fluoroscopy-free biliary cannulation was successful in all 40 patients (100%). Advanced cannulation techniques were required in 5 patients. Papillary balloon dilation was performed in 8 patients and electrohydraulic lithotripsy in 3 patients. Discrete stones were visualized in 31 patients and stone debris/sludge in 8 patients. Fluoroscopy-free stone/debris/sludge extraction was successful in all these patients. Brief fluoroscopy was used in 2 patients (5%) to confirm stone clearance. No stone/debris/sludge was noted in 1 patient. Mild pancreatitis was noted in 2 patients (5%) and bleeding in 1 (2.5%). CONCLUSIONS: This study establishes the feasibility of fluoroscopy/radiation-free, cholangioscopic management of noncomplex choledocholithiasis with success and adverse event rates similar to standard ERCP. DSC represents a significant procedural advance in the management of biliary disorders that does not need to be confined to the fluoroscopy suite and can be reimagined as bedside procedures in emergency department or intensive care unit settings. (Clinical trial registration number: NCT03074201.).

Liver transplant-related anastomotic biliary strictures: a novel, rapid, safe, radiation-sparing, and cost-effective management approach.

BACKGROUND AND AIMS: Biliary strictures after orthotopic liver transplantation (OLT) are typically managed by sequential ERCP procedures, with incremental dilation of the stricture and stent exchange (IDSE) and placement of new stents. This approach resolves >80% of strictures after 12 months but requires costly, lengthy ERCPs with significant patient radiation exposure. Increasing awareness of the harmful effects of radiation, escalating healthcare costs, and decreasing reimbursement for procedures mandate maximal efficiency in performing ERCP. We compared the traditional IDSE protocol with a sequential stent addition (SSA) protocol, in which additional stents are placed across the stricture during sequential ERCPs, without stent removal/exchange or stricture dilation. METHODS: Patients undergoing ERCP for OLT-related anastomotic strictures from 2010 to 2016 were identified from a prospectively maintained endoscopy database. Procedure duration, fluoroscopy time, stricture resolution rates, adverse events, materials fees, and facility fees were analyzed for IDSE and SSA procedures. RESULTS: Seventy-seven patients underwent 277 IDSE and 132 SSA procedures. Mean fluoroscopy time was 64.5% shorter (P < .0001) and mean procedure duration 41.5% lower (P < .0001) with SSA compared with IDSE. SSA procedures required fewer accessory devices, resulting in significantly lower material (63.8%, P < .0001) and facility costs (42.8%, P < .0001) compared with IDSE. Stricture resolution was >95%, and low adverse event rates did not significantly differ. CONCLUSIONS: SSA results in shorter, cost-effective procedures requiring fewer accessory devices and exposing patients to less radiation. Stricture resolution rates are equivalent to IDSE, and adverse events do not differ significantly, even in this immunocompromised population.

Randomized Controlled Trial of Self-directed Versus In-Classroom Education of Narrow Band Imaging in Diagnosing Colorectal Polyps Using the NICE Criteria.

BACKGROUND: The optimal method for teaching NBI International Colorectal Endoscopic (NICE) criteria to medical trainees is unknown. METHODS: Trainees (medical students, residents, and gastroenterology fellows) were randomized to 2 groups (in-classroom vs. self-directed training). Teaching phase: A standardized presentation was developed about narrow band imaging (NBI) and NICE criteria. The in-class teaching group attended a single live-teaching session (with NBI expert). The self-directed training group was provided with the same educational tool with recorded audio. Testing phase: All participants provided their predicted histology and their level of confidence. After completing initial 10 clips, the in-class teaching group received live feedback (NBI expert), whereas the self-teaching group received automated audio feedback. All participants then reviewed the next 30 NBI videos. The diagnostic performance of NBI in predicting histology was compared between the 2 groups. RESULTS: Twenty medical trainees (8 students, 8 residents, and 4 gastroenterology fellows) participated in the study. The overall accuracy, sensitivity, specificity, and negative predictive value in using NBI to predict histology were: 79.0% [95% confidence interval (CI), 76.2-81.8], 69.5% (95% CI, 65.0-74.0), 88.5% (95% CI, 85.3-91.6), and 74.4% (95% CI, 70.4-78.3). There were no significant differences in the performance characteristics between the in-classroom and self-directed groups for all responses including those answered with high confidence. CONCLUSIONS: Using a standardized educational tool, the accuracy of distinguishing adenomatous versus hyperplastic colon polyps using NBI between the in-class teaching and self-directed learning were similar. This suggests that both training methods can be utilized for the education of medical trainees in the use of NICE criteria.

Evolution in the utilization of biliary interventions in the United States: results of a nationwide longitudinal study from 1998 to 2013.

BACKGROUND AND AIMS: Bile duct surgery (BDS), percutaneous transhepatic cholangiography (PTC), and ERCP are alternative interventions used to treat biliary disease. Our aim was to describe trends in ERCP, BDS, and PTC on a nationwide level in the United States. METHODS: We used the National Inpatient Sample to estimate age-standardized utilization trends of inpatient diagnostic ERCP, therapeutic ERCP, BDS, and PTC between 1998 and 2013. We calculated average case fatality, length of stay, patient demographic profile (age, gender, payer), and hospital characteristics (hospital size and metropolitan status) for these procedures. RESULTS: Total biliary interventions decreased over the study period from 119.8 to 100.1 per 100,000. Diagnostic ERCP utilization decreased by 76%, and therapeutic ERCP utilization increased by 35%. BDS rates decreased by 78% and PTC rates by 24%. ERCP has almost completely supplanted surgery for the management of choledocholithiasis. Fatality from ERCP, BDS, and PTC have all decreased, whereas mean length of stay has remained stable. The proportion of Medicare-insured, Medicaid-insured, and uninsured patients undergoing biliary procedures has increased over time. Most of the increase in therapeutic ERCP and decrease in BDS occurred in large, metropolitan hospitals. CONCLUSIONS: Although therapeutic ERCP utilization has increased over time, the total volume of biliary interventions has decreased. BDS utilization has experienced the most dramatic decrease, possibly a consequence of the increased therapeutic capacity and safety of ERCP. ERCPs are now predominantly therapeutic in nature. Large urban hospitals are leading the shift from surgical to endoscopic therapy of the biliary system.

Impact of cap-assisted colonoscopy on detection of proximal colon adenomas: systematic review and meta-analysis.

BACKGROUND AND AIMS: Proximal colon adenomas can be missed during routine colonoscopy. Use of a cap or hood on the tip of the colonoscope has been shown to improve overall adenoma detection with variable rates. However, it has not been systematically evaluated for detection of proximal colon or right-sided adenomas where the cap may have maximum impact on adenoma detection rate (ADR). Our aim was to perform a systematic review and meta-analysis to evaluate the impact of cap-assisted colonoscopy (CC) on right-sided ADRs (r-ADRs) compared with standard colonoscopy (SC). METHODS: PubMed, EMBASE, SCOPUS, and Cochrane databases as well as secondary sources (bibliographic review of selected articles and major GI proceedings) were searched through October 1, 2016. Primary outcome was the pooled rate of r-ADR. Detection of flat adenoma, sessile serrated adenoma/polyp (SSA/P), and number of right-sided adenomas per patient were also assessed. Pooled odds ratio (OR) and 95% confidence intervals (CIs) were calculated using random-effect models. RESULTS: We screened 686 records and analyzed data from 4 studies (CC group, 2546 patients; SC group, 2547 patients) that met criteria for determination of r-ADRs, whereas 6 studies (CC group, 3159 patients; SC group, 3137 patients) were analyzed to estimate right-sided adenomas per patient. r-ADR was significantly higher with CC compared with SC (23% vs 17%; OR, 1.49; 95% CI, 1.08-2.05; I2 = 79%; P = .01). CC also improved detection rates of flat adenoma (OR, 2.08; 95% CI, 1.35-3.20; P < .01) and SSA/P (OR, 1.33; 95% CI, 1.01-1.74; P = .04). The total number of right-sided adenomas (CC: 1428 [60%] vs SC: 1127 [58%]) and number of right-sided adenomas per patient (CC, .71 ± .5, vs SC, .65 ± .62 [mean ± standard deviation]) were numerically higher for CC but were not statistically significant (P = .43). Approximately 17 CCs would be required to detect an additional patient with right-sided adenoma. CONCLUSIONS: Use of CC significantly improves the proximal colon ADR. In addition, flat adenoma and serrated colonic lesion detection rates are also significantly higher as compared with SC.

Normal saline solution versus other viscous solutions for submucosal injection during endoscopic mucosal resection: a systematic review and meta-analysis.

BACKGROUND AND AIMS: EMR is being increasingly practiced for the removal of large colorectal polyps. A variety of solutions such as normal saline solution (NS) and other viscous and hypertonic solutions (VS) have been used as submucosal injections for EMR. A systematic review and meta-analysis is presented comparing the efficacy and adverse events of EMR performed using NS versus VS. METHODS: Two independent reviewers conducted a search of all databases for human, randomized controlled trials that compared NS with VS for EMR of colorectal polyps. Data on complete en bloc resection, presence of residual lesions, and adverse events were extracted using a standardized protocol. Pooled odds ratio (OR) estimates along with 95% confidence intervals (CI) were calculated using fixed effect or random effects models. RESULTS: Five prospective, randomized controlled trials (504 patients) met the inclusion criteria. The mean polyp sizes were 20.84 mm with NS and 21.44 mm with VS. On pooled analysis, a significant increase in en bloc resection (OR, 1.91; 95% CI, 1.11-3.29; P = .02; I2 = 0%) and decrease in residual lesions (OR, 0.54; 95% CI, 0.32-0.91; P = .02; I2 = 0%) were noted in VS compared with NS. There was no significant difference in the rate of overall adverse events between the 2 groups. CONCLUSIONS: Use of VS during EMR leads to higher rates of en bloc resection and lower rates of residual lesions compared with NS, without any significant difference in adverse events. Endoscopists could consider using VS for EMR of large colorectal polyps and NS for smaller polyps because there is no significant difference in the outcomes with lesions <2 cm.

Efficacy and safety outcomes of multimodal endoscopic eradication therapy in Barrett's esophagus-related neoplasia: a systematic review and pooled analysis.

BACKGROUND AND AIMS: Focal EMR followed by radiofrequency ablation (f-EMR + RFA) and stepwise or complete EMR (s-EMR) are established strategies for eradication of Barrett's esophagus (BE)-related high-grade dysplasia (HGD) and/or esophageal adenocarcinoma (EAC)/intramucosal carcinoma (IMC). The objective of this study was to derive pooled rates of efficacy and safety of individual methods in a large cohort of patients with BE and to indirectly compare the 2 methods. METHODS: PubMed, Embase, Web of Science, Cochrane, and major conference proceedings were searched. A systematic review and pooled analysis were carried out to determine the following outcomes in patients with BE undergoing either f-EMR + RFA or s-EMR: (1) complete eradication rates of neoplasia (CE-N) and intestinal metaplasia (CE-IM); (2) recurrence rates of cancer (EAC), dysplasia, and IM; (3) incidence rates of adverse events. Mixed logistic regression was performed as an exploratory analysis to examine differences in outcomes between the 2 methods. RESULTS: Nine studies (774 patients) of f-EMR + RFA and 11 studies (751 patients) of s-EMR were included. Patients undergoing f-EMR + RFA had high BE eradication rates (CE-N, 93.4%; CE-IM, 73.1%), whereas strictures occurred in 10.2%, bleeding in 1.1%, and perforations in 0.2% of patients. Recurrence of EAC, dysplasia, and IM was 1.4%, 2.6%, and 16.1%, respectively, in this group. Patients undergoing s-EMR also showed high BE eradication rates (CE-N, 94.9%; CE-IM, 79.6%) but a higher rate of adverse events (strictures in 33.5%, bleeding in 7.5%, and perforation in 1.3%). Recurrence of EAC, dysplasia, and IM was 0.7%, 3.3%, and 12.1%, respectively, in the s-EMR group. Mixed logistic regression showed that patients undergoing s-EMR might be more likely to develop esophageal strictures (odds ratio [OR], 4.73; 95% confidence interval [CI], 1.61-13.85; P = .005), perforation (OR, 7.00; 95% CI, 1.56-31.33; P = .01), and bleeding (OR, 6.88; 95% CI, 2.19-21.62; P = 0.001) compared with f-EMR + RFA. CONCLUSIONS: In patients with HGD/EAC, f-EMR followed by RFA seems to be equally effective as and safer than s-EMR.

Feeding after percutaneous endoscopic gastrostomy: experience of early versus delayed feeding.

BACKGROUND: Multiple studies have demonstrated that feeding ≤4 hours after placement of a percutaneous endoscopic gastrostomy (PEG) tube is a reasonable option. Many physicians, however, continue to delay feedings until the next day or 24 hours; therefore, we evaluated the safety and effect of early feeding (≤4 hours) after PEG placement in our tertiary care center. METHODS: A retrospective study of 444 patients who underwent PEG between June 2006 and December 2011 was performed. Early feeding was defined as feeding ≤4 hours and delayed feeding was defined as feeding >4 hours. Statistical analysis was performed using the Fisher exact test and the Student t test. RESULTS: A total of 444 patients underwent PEG between June 2006 and December 2011. A majority of PEGs were performed on inpatients by gastroenterologists. The mean time of feeding after PEG was 3.2 ± 0.9 hours for the early group (n = 197) and 17.0 ± 10.0 hours for the delayed group (n = 247). No statistically significant differences were noted between the early (≤4 hours) feedings versus the delayed (>4 hours) feedings for overall morality within 30 days (P = 0.72) and overall complications (P = 1.00). Furthermore, no statistically significant differences were noted between early versus delayed feeding for 24-hour mortality (P = 1.00), 24- to 72-hour mortality (P = 0.20), and 3-30 days mortality (P = 0.86). For each complication, there were no statistically significant differences noted between the two groups for wound infection (P = 0.52), melena (P = 0.26), vomiting (P = 0.42), leakage (P = 0.41), stomatitis (P = 0.13), aspiration pneumonia (P =1.00), and other complications (P = 0.47). CONCLUSIONS: Feeding ≤4 hours after PEG appears to be as safe as delayed feeding. Based on this study and the literature, strong consideration for the majority of patients should be undertaken to begin feeding within 4 hours after PEG.

A Comprehensive Review of Total Hip Arthroplasty Outcomes in Post-traumatic Hip Arthritis: Insights and Perspectives.

Post-traumatic hip arthritis presents a challenging condition characterized by degenerative changes in the hip joint following traumatic injury. Total hip arthroplasty (THA) is a cornerstone in managing this condition, offering significant pain relief, functional improvement, and enhanced quality of life. This comprehensive review aims to synthesize existing literature to elucidate the outcomes of THA in post-traumatic hip arthritis, exploring factors influencing surgical success and identifying areas for further research. Key findings reveal favourable clinical outcomes associated with THA, though considerations such as patient characteristics, surgical techniques, and implant selection impact outcomes. Implications for clinical practice underscore the importance of tailored preoperative assessment and ongoing advancements in surgical approaches and implant technology. Furthermore, opportunities for future research lie in long-term durability studies, patient-reported outcomes assessment, and exploration of innovative surgical techniques. Overall, THA emerges as a promising intervention for post-traumatic hip arthritis, yet continual refinement through research and innovation remains imperative to optimize patient care in this population.

Optimizing Acetabular Positioning: A Comprehensive Review of Contemporary Strategies in Total Hip Arthroplasty.

Total hip arthroplasty (THA) is a widely practiced surgical intervention to alleviate pain and reinstate functionality in individuals afflicted with hip joint pathology. The positioning of the acetabulum assumes paramount significance in determining the efficacy of THA, exerting profound influences on biomechanical dynamics, stability, and the durability of outcomes over time. This comprehensive review meticulously evaluates contemporary methodologies for optimizing acetabular positioning in THA, encompassing advanced technologies such as computer-assisted navigation systems, patient-specific instrumentation, robotic-assisted surgical approaches, image-based planning techniques, and intraoperative fluoroscopy. Crucially, key discoveries underscore the pivotal role of precise acetabular alignment in mitigating complications such as dislocation, component wear, and impingement. Moreover, the implications for clinical practice accentuate the imperative of continuous education and training to ensure effective deployment of sophisticated methodologies. Recommendations for furthering research and enhancing practice development underscore the necessity of scrutinizing long-term prognoses, assessing cost-effectiveness, and embracing technological innovations perpetually refining THA outcomes. Collaborative endeavors among researchers, practitioners, and industry stakeholders emerge as indispensable drivers of advancement in this domain, fostering an environment conducive to elevating the standard of care for individuals undergoing THA.

Extralobar Pulmonary Sequestration: A Rare Entity.

Lung sequestration is a rare congenital anomaly characterized by non-functional lung tissue that lacks normal bronchial communication and receives blood supply from an aberrant systemic artery. Extralobar sequestration (ELS) is less common and usually found in the lower thoracic or upper abdominal regions. It is often diagnosed in infancy or early childhood due to associated congenital anomalies or respiratory symptoms. The complexity of highly variable anatomy and the involvement of multiple systemic arteries pose significant diagnostic and therapeutic challenges. Patients may present with a variety of nonspecific symptoms, such as recurrent respiratory infections, chronic coughs, or unexplained abdominal pain, which often leads to delayed diagnosis. This case report details the unique presentation of extrapulmonary lung sequestration in a 32-year-old male who presented with persistent respiratory symptoms and intermittent abdominal discomfort. Through comprehensive imaging studies and surgical intervention, the diagnosis was confirmed, and the sequestered tissues were successfully resected. This report aims to highlight the importance of considering bilateral extrapulmonary sequestration in differential diagnoses of recurrent respiratory and abdominal symptoms and to discuss the diagnostic approach and management strategies for this rare condition with highly variable anatomy.

Early versus delayed percutaneous coronary intervention for patients with non-ST segment elevation acute coronary syndrome: a meta-analysis of randomized controlled clinical trials.

BACKGROUND: Studies assessing the timing of percutaneous coronary interventions (PCI) in patients with Non-ST segment elevation Acute Coronary Syndromes (NSTE-ACS) have failed to generate a consensus on how early PCI should be performed in such patients. PURPOSE: This meta-analysis compares clinical outcomes at 30 days in NSTE-ACS patients undergoing PCI within 24 hours of presentation (early PCI) with those receiving PCI more than 24 hours after presentation (delayed PCI). DATA SOURCES: Data were extracted from searches of MEDLINE (1990-2010) and Google scholar and from scrutiny of abstract booklets from major cardiology meetings (1990-2010). STUDY SELECTION: Randomized clinical trials (RCTs) that included the composite endpoint of death and non-fatal myocardial infarction (MI) at 30 days after PCI were considered. DATA EXTRACTION: Two independent reviewers extracted data using standard forms. The effects of early and delayed PCI were analyzed by calculating pooled estimates for death, non-fatal MI, bleeding, repeat revascularization and the composite endpoint of death or non-fatal MI at 30 days. Univariate analysis of each of these variables was used to create odds ratios. DATA SYNTHESIS: Seven studies with a total of 13,762 patients met the inclusion criteria. There was no significant difference in the odds of the composite endpoint of death or non-fatal MI at 30 days between patients undergoing early PCI and those receiving delayed PCI (OR-0.83, 95%CI 0.62-1.10). Patients receiving delayed PCI experienced a 33% reduction in the odds of repeat revascularization at 30 days compared to those undergoing early PCI (OR-1.33, 95%CI 1.14-1.56, P=0.0004).Conversely, patients undergoing early PCI experienced lower odds of bleeding than those receiving delayed PCI (OR-0.76, 95%CI 0.63-0.91, P = 0.0003). CONCLUSIONS: In NSTE-ACS patients early PCI doesn't reduce the odds of the composite endpoint of death or non-fatal MI at 30 day. This strategy is associated with lower odds of bleeding and higher odds of repeat revascularization at 30 days than a strategy of delayed PCI.