Citations

Stenosis of the left main coronary artery (LM stenosis) is associated with significant mortality and morbidity due to the large area of affected myocardium. Evidence on the use of percutaneous coronary intervention (PCI) for the treatment of LM stenosis is growing. However, the role of Western guidelines on patients in the Asian-Pacific region is unclear due to anatomical variations, substantial heterogeneity in healthcare resources and infrastructure, and the lack of consensus on the optimal management of LM stenosis in the Asia-Pacific region. Hence, an Asian Pacific Society of Cardiology (APSC) working group developed consensus recommendations on the use of PCI in the management of LM stenosis in the Asia-Pacific region. The APSC expert panel reviewed and appraised the available evidence using the Grading of Recommendations Assessment, Development, and Evaluation system. Consensus recommendations were developed and put to an online vote. Consensus was reached when 80% of votes for a given recommendation were in support of ‘agree’ or ‘neutral’. The resulting 12 statements provide guidance for clinical practitioners in the region on the use of PCI in the treatment of patients with LM stenosis.

Objective: To assess the efficacy and safety of corticosteroids for the management of pediatric sepsis and septic shock. Data Sources: Ovid MEDLINE, Ovid Embase, CENTRAL, Web of Science (Core Collection) and China National Knowledge Infrastructure were systematically searched up to September 2023. Preprint servers, clinical trial registries and the reference sections of previous reviews were hand-searched. Study Selection: Randomized controlled trials that enrolled pediatric sepsis, septic shock or systemic inflammatory response syndrome patients, compared the use of corticosteroid regimens against standard sepsis care and reported eligible outcomes were included. Title/abstract and full-text screening were conducted in-duplicate. Data Extraction: Eligible articles were extracted using a standardized form in-duplicate. Outcomes extracted include mortality incidence, hospital and pediatric intensive care unit length of stay, duration of shock, incidence of adverse events and serious adverse events and incidence of corticosteroid-related adverse events. The risk of bias was assessed using the Revised Cochrane Risk of Bias Tool for Assessing Randomized Trials. Data Synthesis: Random-effects meta-analyses were conducted, and the quality of evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluations approach. Sixteen randomized controlled trials (N = 973) were included. Corticosteroid use may be associated with reduced mortality risks (risk ratio: 0.65, 95% CI: 0.50–0.85), shorter length of hospital stay (MD: −3.76 days, 95% CI: −6.66 to −0.86), and shorter pediatric intensive care unit length of stay (MD −2.34 days, 95% CI: −3.14 to −1.53 days). Corticosteroid use may be associated with gastrointestinal bleeding but not a higher risk of secondary infection. No studies reported on serious adverse events. All findings were based on low to very low quality of evidence. Conclusions: While corticosteroids show promise for managing pediatric sepsis and septic shock, the question of how to select the best candidate and the most optimal regimen remains unanswered. Future trials need to focus on assessing corticosteroid-related adverse events and stratifying patient inclusion by sepsis subphenotypes.

BACKGROUND: Long QT syndrome is a lethal arrhythmia syndrome, frequently caused by rare loss-of-function variants in the potassium channel encoded by KCNH2 . Variant classification is difficult, often because of lack of functional data. Moreover, variant-based risk stratification is also complicated by heterogenous clinical data and incomplete penetrance. Here we sought to test whether variant-specific information, primarily from high-throughput functional assays, could improve both classification and cardiac event risk stratification in a large, harmonized cohort of KCNH2 missense variant heterozygotes. METHODS: We quantified cell-surface trafficking of 18 796 variants in KCNH2 using a multiplexed assay of variant effect (MAVE). We recorded KCNH2 current density for 533 variants by automated patch clamping. We calibrated the strength of evidence of MAVE data according to ClinGen guidelines. We deeply phenotyped 1458 patients with KCNH2 missense variants, including QTc, cardiac event history, and mortality. We correlated variant functional data and Bayesian long QT syndrome penetrance estimates with cohort phenotypes and assessed hazard ratios for cardiac events. RESULTS: Variant MAVE trafficking scores and automated patch clamping peak tail currents were highly correlated (Spearman rank-order ρ=0.69; n=433). The MAVE data were found to provide up to pathogenic very strong evidence for severe loss-of-function variants. In the cohort, both functional assays and Bayesian long QT syndrome penetrance estimates were significantly predictive of cardiac events when independently modeled with patient sex and corrected QT interval (QTc); however, MAVE data became nonsignificant when peak tail current and penetrance estimates were also available. The area under the receiver operator characteristic curve for 20-year event outcomes based on patient-specific sex and QTc (area under the curve, 0.80 [0.76–0.83]) was improved with prospectively available penetrance scores conditioned on MAVE (area under the curve, 0.86 [0.83–0.89]) or attainable automated patch clamping peak tail current data (area under the curve, 0.84 [0.81–0.88]). CONCLUSIONS: High-throughput KCNH2 variant MAVE data meaningfully contribute to variant classification at scale, whereas long QT syndrome penetrance estimates and automated patch clamping peak tail current measurements meaningfully contribute to risk stratification of cardiac events in patients with heterozygous KCNH2 missense variants.

Background: Question prompt lists (QPLs) are structured sets of disease-specific questions intended to encourage question-asking by patients and enhance patient-physician communication. To date, an EoE-specific QPL has not been developed for EoE patients. Aim: To develop a preliminary QPL specific to adults with EoE by incorporating input from international esophageal experts. Methods: Sixteen experts were invited to generate QPL content through a modified Delphi (RAND/University of California, Los Angeles, CA) method consisting of 2 rounds of independent ratings. In round 1, experts provided 5 answers to the prompts “what general questions should patients ask when being seen for EoE?” and “what questions do I not hear patients asking but given my experience, I believe they should be asking?” In round 2, experts rated each question on a 5-point Likert scale, and responses rated as “essential” or “important” (determined by an a priori median threshold of ≥ 4.0) were accepted for the EoE QPL. Results: Ten esophageal experts participated in both rounds. Round 1 generated 100 questions. Questions were combined and modified to reduce redundancy, yielding 57 questions. After round 2, 51 questions (85%) were accepted for inclusion (median value ≥ 4.0) in the final QPL. Questions were then divided into 4 themes based on disease domains: (1) “What is EoE?,” (2) “Treatment Options,” (3) “Follow-up Surveillance and Long-term Risks,” and (4) “Allergy and Genetic Testing.” The largest number of questions covered was “What is EoE?” (16/51 or 31%). Questions with the highest agreement median (5.0) included examples such as “what should I do if I get a food impaction?” and “what are the treatment options?” Conclusion: This is the first preliminary EoE QPL developed in the field of medicine. We hope implementation enhances effective patient-physician communication by encouraging patients to ask relevant questions that experts prioritized. Future studies will aim to modify this communication tool by incorporating patient perspectives

ABSTRACT The management of hepatic adenoma in transgender individuals undergoing gender-affirming hormone therapy remains unclear, especially whether treatment should be based on sex assigned at birth or therapy patient received. We presented a transgender man, female at birth, with hepatic adenomatosis with molecular profile differed from typical adenomas in cisgender males on testosterone. Discontinuing testosterone led to autoinfarction of the adenoma, allowing the avoidance of invasive treatments and resumption of gender-affirming hormone therapy. This case underscores the necessity for personalized care in the growing transgender population and challenges current consensus of treatment based on sex assigned at birth, emphasizing a tailored approach.

Background: Within the spectrum of gastroesophageal reflux disease (GERD), pathologic reflux applies to the subset of patients with either erosive esophagitis or abnormal esophageal acid exposure on pH-metry, consequences of a dysfunctional antireflux barrier (ARB). Methods: The American Foregut Society (AFS) tasked a 13-member working group of expert foregut surgeons and esophagologists (The ARB Cooperative) to develop a white paper on ARB function, dysfunction, and mechanisms of action of antireflux surgery through discussion of relevant literature summarized herein. Results: The ARB Cooperative concluded that pathologic reflux is a consequence of the interplay between progressive anatomical distortion of the ARB and physiology. Factors contributing to ARB dysfunction include (1) separation of crural diaphragm from the lower esophageal sphincter with widening of the hiatus and diminished crural diaphragm sphincteric function; (2) loss of the intra-abdominal lower esophageal sphincter segment with complete disabling of the flap valve component of the ARB; (3) axial hiatal hernia leading to reflux during swallow-induced lower esophageal sphincter (LES) relaxation, LES hypotension, inspiration related reflux, a lowered threshold for eliciting transient LES relaxations, and increased compliance of the gastroesophageal junction leading to greater diameter of sphincter opening during transient LES relaxations. With regard to antireflux surgery, the objectives include: (1) reduction of hiatal hernia and restoration of the intra-abdominal esophageal segment; (2) repair of the dilated hiatus; (3) restoring flap valve function by modifying gastroesophageal anatomy; and (4) restricting gastroesophageal junction opening during periods of relaxation. Conclusions: This ARB Cooperative white paper supports the concept of there being 3 major inter-related mechanisms promoting ARB competence: the LES as an intrinsic sphincter, the crural diaphragm as an extrinsic sphincter, and the gastroesophageal valve, a mechanical 1-way valve. Pathological reflux occurs with progressive anatomical disruption of the ARB which in turn leads to physiological dysfunction, the severity of which parallels the extent of anatomical disruption. The corollary of this is that the primary mechanism of antireflux surgery is to restore the ARB by eliminating or compensating for its anatomical disruption. It is the hope of the cooperative that understanding the proposed framework will help clinicians and researchers in improving antireflux procedures.

Abstract Background GERD is a common cause of chronic cough. Although barrier therapy with laparoscopic fundoplication is highly effective for typical GERD symptoms, the response rates are variable for chronic cough. We hypothesized that transoral incisionless fundoplication (TIF) or TIF with hiatal hernia repair (cTIF) may be a suitable alternative for medically refractory cough associated with GERD. Aim We prospectively s studied the effectiveness and safety of TIF/cTIF in patients with chronic cough and proven GERD. Methods Patients with GERD and extra-esophageal symptoms from 10 academic and community medical centers (TIF Registry), elevated GERD-HRQL score +/- Reflux Symptom Index (RSI) >13 and pathologic reflux by esophageal pH-metry, or erosive esophagitis/Barrett’s esophagus were evaluated before and after a minimum 6 months post TIF/cTIF performed by gastroenterologists and surgeons. Patients with history of prior foregut/bariatric surgery, chronic obstructive or interstitial lung disease, or prior lung transplant were excluded. The primary outcome was improvement in RSI score at last follow-up compared to baseline. Secondary outcomes were: 1) normalization of RSI (<13), 2) improvement in cough sub-scores of RSI (decrease ≥ 2 points or to 0 on a 5-point scale), 3) GERD symptom improvement (>50% decrease in GERD-HRQL, or < 2 in all sub-scores) 4) discontinuation of proton pump inhibitor (PPI), and 5) overall patient satisfaction. We further analyzed response in patients with cough-predominant phenotype (chief complaint of cough and RSI troublesome cough subscore ≥2). Results 198 patients with cough and GERD successfully underwent TIF/cTIF (Table 1) without serious adverse events. Greater than 6-month follow-up was available for 177 patients at a median of 12 months [IQR 6,12]. Median RSI score decreased from 18 [IQR 13, 27] to 5 [IQR 2, 11] (p < 0.0001), median change 11 [IQR5,11]. 83% of patients with elevated baseline RSI normalized their scores. 75% of patients had improvement of cough when lying down (median: 1 point [IQR 0,3]), and 72% of patients had improvement of troublesome cough (median: 1 point [IQR 1,3]). 83% of patients successfully discontinued or decreased PPI to occasional use. Patient satisfaction improved from a baseline of 5.6% to 68.8% (p <0.0001). Compared to patients without cough-predominant symptoms, cough-predominant patients (n=108) experienced an additional 4.2-point decrease in in RSI score (p = 0.01) and 1.5-point decrease in troublesome cough sub-scores (p<0.0001). Patients with regurgitation phenotype were more likely to have a favorable cough response at 6 months (p<0.0001). In appropriately selected patients, cTIF and TIF were comparable for cough, GERD-HRQL, RSI, and PPI responses. Conclusion TIF/cTIF are effective and safe alternative barrier therapies for patients with pH-positive cough-predominant GERD.

Abstract The significance of anterior cruciate ligament (ACL) remnants during reconstruction remains unclear. Co‐culturing ACL remnant cells and bone marrow stromal cells (BMSCs) may reduce apoptosis and enhance hamstring tendon activity. This study investigated whether extracellular vesicles (EVs), which facilitate cell–cell interactions, act as the active components, improving graft maturation in this co‐culture. The effects of EVs on cell viability, proliferation, migration and gene expression in the rabbit ACL remnant cells and BMSCs were assessed using control (BMSC‐only culture), co‐culture (ACL remnant cells and BMSCs, CM) and co‐culture without EVs (CM ∆ EVs) media. EVs were isolated from control (BMSC‐EV) and co‐culture (CM‐EV) media and characterized. CM significantly enhanced the proliferation, migration and expression of transforming growth factor ( TGF‐β )‐, vascular endothelial growth factor ( VEGF )‐, collagen synthesis‐ and tenogenesis‐related genes. However, CM‐induced effects were reversed by the CM ∆ EVs treatment. CM‐EV treatment exhibited higher potential to enhance proliferation, migration and gene expression in the ACL remnant cells and BMSCs than BMSC‐EV and non‐EV treatments. In conclusion, EVs, secreted under the coexistence of ACL remnant cells and BMSCs, primarily increase the cell viability, proliferation, migration and gene expression of collagen synthesis‐, TGF‐β ‐, VEGF ‐ and tenogenesis‐related genes in both cell types.