Rare,Overlooked, or Underappreciated Causes of Recurrent Abdominal Pain: A Primer for Gastroenterologists

Recurrent abdominal pain is a common reason for repeated visits to outpatient clinics and emergency departments, reflecting a substantial unmet need for timely and accurate diagnosis. A lack of awareness of some of the rarer causes of recurrent abdominal pain may impede diagnosis and delay effective management. This article identifies some of the key rare but diagnosable causes that are frequently missed by gastroenterologists and provides expert recommendations to support recognition, diagnosis, and management with the ultimate aim of improving patient outcomes.     

Development and Validation of a Score for Fibrotic Nonalcoholic Steatohepatitis

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Randomized Trials Are Needed for Transcatheter Mitral Valve Replacement

Transcatheter mitral valve replacement (TMVR) is a new therapy for treating symptomatic mitral regurgitation (MR) and stenosis. The proposed benefit of TMVR is the predictable, complete elimination of MR, which is less certain with transcatheter repair technologies such as TEER (transcatheter edge-to-edge repair). The potential benefit of MR elimination with TMVR needs to be rigorously evaluated against its risks which include relative procedural invasiveness, need for anticoagulation, and chronic structural valve deterioration. Randomized controlled trials (RCTs) are a powerful method for evaluating the safety and effectiveness of TMVR against current standard of care transcatheter therapies, such as TEER. RCTs not only help with the assessment of benefits and risks, but also with policies for determining operator or institutional requirements, resource utilization, and reimbursement. In this paper, the authors provide recommendations and considerations for designing pivotal RCTs for first-in-class TMVR devices.     

Serum HBcrAg and Hepatocellular Carcinoma in a Taiwanese Population Seronegative for HBsAg and Anti-HCV

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Monoclonal Autoantibody Against a Cryptic Epitope on Tissue-Adherent Low-Density Lipoprotein for Molecular Imaging in Atherosclerosis

BackgroundAntibody-based constructs for molecular imaging and therapeutic delivery provide promising opportunities for the diagnosis and treatment of atherosclerosis.ObjectivesThe authors aimed to generate and characterize immunoglobulin (Ig)G monoclonal autoantibodies in atherosclerosis for targeting of novel molecular determinants.MethodsThe authors created hybridomas from an unimmunized low-density lipoprotein (LDL) receptor-deficient (Ldlr^?/?) mouse and selected an IgG2b isotype autoantibody, LO9, for further characterization.ResultsLO9 reacted well with native LDL bound to immobilized matrix components and less well to oxidized LDL. LO9 binding to immobilized native LDL was not neutralized by fluid-phase native LDL, indicating an adhesion-dependent epitope. The authors localized the epitope to a 20 amino-acid peptide sequence (P5) in the globular amino-terminus of apolipoprotein B. LO9 reacted with antigen in mouse atherosclerosis and in both human stable and ruptured coronary atherosclerosis. Furthermore, in vivo near-infrared fluorescence molecular tomographic imaging, and ex vivo confocal microscopy showed that intravenously injected LO9 localized beneath endothelium of the aortic arch in Ldlr^?/? mice, in the vicinity of macrophages.ConclusionsThe authors believe LO9 is the first example of an IgG autoantibody that reacts with a native LDL epitope revealed by adherence to tissue matrix. Antibodies against adherent native LDL have potential as molecular targeting agents for imaging of and therapeutic delivery to atherosclerosis.     

New and Emerging Therapies for Reduction of LDL-Cholesterol and Apolipoprotein B: JACC Focus Seminar 1/4

Adding to the foundation of statins, ezetimibe and proprotein convertase subtilisin–kexin type 9 inhibitors (PCSK9i), novel, emerging low-density lipoprotein cholesterol (LDL-C)–lowering therapies are under development for the prevention of cardiovascular disease. Inclisiran, a small interfering RNA molecule that inhibits PCSK9, only needs to be dosed twice a year and has the potential to help overcome current barriers to persistence and adherence to lipid-lowering therapies. Bempedoic acid, which lowers LDL-C upstream from statins, provides a novel alternative for patients with statin intolerance. Angiopoetin-like 3 protein (ANGPTL3) inhibitors have been shown to provide potent LDL-C lowering in patients with homozygous familial hypercholesterolemia without major adverse effects as seen with lomitapide and mipomersen, and may reduce the need for apheresis. Finally, CETP inhibitors may yet be effective with the development of obicetrapib. These novel agents provide the clinician the tools to effectively lower LDL-C across the entire range of LDL-C–induced elevation of cardiovascular risk, from primary prevention and secondary prevention to null-null homozygous familial hypercholesterolemia patients.     

Underwater versus conventional EMR for colorectal polyps: systematic review and meta-analysis

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Perspective on the clone library method for infectious diseases

Recently, culture-independent molecular methods, such as DNA sequencing techniques targeting the 16S-ribosomal RNA (rRNA) gene and/or other housekeeping genes with Sanger method-based technologies, next generation sequencing (NGS), and metagenomic analysis, have been developed for detecting microorganisms in the human body; these can provide information on microbiomes of samples from individuals with or without infectious diseases. Determining the bacterial species is crucial in identifying causative bacteria of upper and lower respiratory tract infections, especially for Streptococcus species, but NGS analysis is often not precise enough to identify bacteria at the species level. This review briefly introduces previous observations of the microbiome of samples from various respiratory and other infections assessed using the clone library method with Sanger sequencing of the 16S-rRNA gene. On analysis of 16S-rRNA gene-sequence data of bronchoalveolar lavage fluid obtained from pneumonia lesions in patients with bacterial pneumonia and lung abscess, anaerobes are often detected in non-elderly patients with pneumonia, and the detection rate of Staphylococcus aureus in patients with hospital-acquired pneumonia is lower than that previously reported. Analysis of pleural effusion samples from patients with pleurisy indicated a more important role of anaerobes than previous believed. The other topics reviewed include microbiomes of nontuberculous mycobacteriosis and lower respiratory tract infections in children with permanent tracheostomy due to neuromuscular disorders, in nasal discharge, in bacterial vaginosis, in the intracystic fluid of postoperative maxillary cyst, and in bacterial conjunctivitis; urine microbiota in urethritis; fecal microbiota; and newly detected infectious organisms in the human respiratory tract.     

Transcatheter Intervention for Congenital Defects Involving the Great Vessels: JACC Review Topic of the Week

Since the development of balloon angioplasty and balloon-expandable endovascular stent technology in the 1970s and 1980s, percutaneous transcatheter intervention has emerged as a mainstay of therapy for congenital heart disease (CHD) lesions throughout the systemic and pulmonary vascular beds. Congenital lesions of the great vessels, including the aorta, pulmonary arteries, and patent ductus arteriosus, are each amenable to transcatheter intervention throughout the lifespan, from neonate to adult. In many cases, on-label devices now exist to facilitate these therapies. In this review, we seek to describe the contemporary approach to and outcomes from transcatheter management of major CHD lesions of the great vessels, with a focus on coarctation of the aorta, single- or multiple-branch pulmonary artery stenoses, and persistent patent ductus arteriosus. We further comment on the future of transcatheter therapies for these CHD lesions.     

Biologics for Inflammatory Bowel Disease and Their Safety in Pregnancy: A Systematic Review and Meta-analysis

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Right Ventricular Contraction Patterns in Patients Undergoing Transcatheter Tricuspid Valve Repair for Severe Tricuspid Regurgitation

ObjectivesThis study investigated patterns of right ventricular (RV) contraction by using cardiac magnetic resonance (CMR) imaging in patients undergoing transcatheter tricuspid valve repair (TTVR).BackgroundThe role of RV function in patients with severe tricuspid regurgitation undergoing TTVR is poorly understood.MethodsGlobal RV dysfunction was defined as CMR-derived RV ejection fraction (RVEF) ≤45% and longitudinal RV dysfunction was defined as tricuspid annular plane systolic excursion (TAPSE) <17 mm on echocardiography. Patients were stratified into 3 types of RV contraction: type I, TAPSE ≥17 and RVEF >45%; type II, TAPSE <17 and RVEF >45%; and type III, TAPSE <17 and RVEF ≤45%. CMR feature tracking was performed to assess longitudinal and circumferential RV strain. The primary outcome was a composite of all-cause mortality or first heart failure hospitalization.ResultsOf 79 patients (median age 79 years, 51% female), 18 (23%) presented with global and 40 (51%) presented with longitudinal RV dysfunction. The composite outcome occurred in 22 patients (median follow-up 362 days). Global RV dysfunction but not longitudinal RV dysfunction (hazard ratio: 6.62; 95% confidence interval: 2.77-15.77; and hazard ratio: 1.30; 95% confidence interval: 0.55-3.08, respectively) was associated with the composite outcome. Compared with type I RV contraction, patients with type II RV contraction exhibited increased circumferential strain, with a preservation of RVEF despite diminished longitudinal strain. Patients with type III RV contraction exhibited both diminished longitudinal and circumferential strain, resulting in an impaired RVEF. Patients with type III RV contraction showed the worst survival (P < 0.001).ConclusionsGlobal RV dysfunction is a predictor of outcomes among TTVR patients. Tricuspid regurgitation patients can be stratified into 3 types of RV contraction, in which a loss of longitudinal function can be compensated by increasing circumferential function, preserving RVEF and favorable outcomes.