Metabolic abnormalities,but not obesity per se,associated with chronic kidney disease in a Taiwanese population

Background and aimsIt is inconclusive whether obesity itself or metabolic abnormalities are linked to chronic kidney disease (CKD). The aim of this study was to examine the association between different subtypes of obesity and metabolic abnormalities with CKD in adults.Methods and resultsThis study enrolled 14,983 eligible subjects stratified into metabolically healthy normal weight (MHNW), metabolically healthy overweight (MHOW), metabolically healthy obesity (MHO), metabolically unhealthy normal weight (MUNW), metabolically unhealthy overweight (MUOW), and metabolically unhealthy obesity (MUO) according to body mass index and metabolic syndrome status (ATP-III criteria). The metabolic healthy phenotype was defined as the absence of both metabolic syndrome and any known diabetes, coronary artery disease, stroke, hypertension or dyslipidemia. Early and advanced CKD were defined as eGFR<60, proteinuria, or structural abnormalities as detected by renal sonography. The prevalence of CKD was 2.5, 3.0, 4.0, 10.6, 9.5, and 10.5% in subjects with MHNW, MHOW, MHO, MUNW, MUOW, and MUO, respectively. In the multivariate analysis, the MUNW (OR:2.22, P < 0.001), MUOW (OR:2.22, P < 0.001), and MUO (OR:2.45, P < 0.001) groups were associated with early CKD. For advanced CKD, the OR was 2.56 (P < 0.001), 2.31 (P < 0.001), and 3.49 (P < 0.001) in the MUNW, MUOW, and MUO groups, respectively. The associated risks of early and advanced CKD were not significant in the MHOW and MHO group. MUOW and MUO were associated with higher risk of CKD compared with MHOW and MHO after adjusting other variables.ConclusionsMetabolic abnormalities, but neither overweight nor obesity, were associated with a higher risk of CKD in adults.     

Diagnostic yield and therapeutic impact of novel motorized spiral enteroscopy in small-bowel disorders: a single-center,real-world experience from a tertiary care hospital (with video)

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Transcatheter Mitral Valve Replacement: An Update on Current Techniques,Technologies, and Future Directions

Growing clinical data support the use of transcatheter therapies for significant mitral valve disease. Currently, edge-to-edge repair is the transcatheter treatment of choice, but many anatomies are not suitable. Transcatheter mitral valve replacement offers several potential advantages over transcatheter repair, most notably a greater and more sustained reduction in mitral regurgitation post-implantation, but also potential disadvantages. To enable the successful treatment of mitral valve disease in a wide range of patients and anatomies, we require an armory of transcatheter devices, including transcatheter mitral valve replacement systems.     

Clinical characteristics,outcomes, and factors associated with mortality in Nocardia pneumonia: 18 years' real-world data from a tertiary care hospital in Karachi,Pakistan

BackgroundPulmonary nocardiosis is a rare pulmonary infection with high morbidity and mortality. Limited real-world data on pulmonary nocardiosis patients are available from developing countries like Pakistan.MethodsThis retrospective observational study was conducted at the Aga Khan University Hospital, Karachi, Pakistan, from August 2003 to June 2020. Demographics, immune status, underlying diseases, laboratory data, treatment, and outcomes of all nocardiosis patients were recorded in predesigned proforma.ResultsSixty-six patients with smear/culture-proven pulmonary nocardiosis were identified. Most patients (83.3%) were treated with trimethoprim-sulfamethoxazole alone or in combination with other medicines. The overall mortality rate in our study was 33.3% (n = 22/66). Factors significantly associated with mortality were respiratory failure (p < 0.001), raised procalcitonin levels (p = 0.01), concomitant fungal infections (p = 0.01), concomitant TB (p = 0.03), and patients on combination therapy (p < 0.001).Respiratory failure (odds ratio [OR] 46.94 [95% confidence intervals [CI]: 5.01–439.03] p < 0.001), concomitant fungal infection (OR 17.09 [95% CI: 1.47–197.88] p- = 0.02) and patients on combination therapy (OR 6.90 [95% CI: 1.23–38.61] p = 0.02) were also identified as independent risk factors for mortality on multivariate analysis.ConclusionsThis study provides essential information on the clinical characteristics and risk factors, outcomes, and factors associated with mortality for pulmonary nocardial infections.     

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.     

Efficacy and Safety of Aldafermin,an Engineered FGF19 Analog,in a Randomized,Double-Blind,Placebo-Controlled Trial of Patients With Nonalcoholic Steatohepatitis

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Effects of mixed nut consumption on LDL cholesterol,lipoprotein(a), and other cardiometabolic risk factors in overweight and obese adults

Background and aimsElevated LDL-C, lipoprotein(a) [Lp(a)], and inflammation are associated with greater risk for atherosclerotic cardiovascular events. Consumption of individual nut types decreases these risk factors but knowledge about the effect of mixed nuts on Lp(a) is limited. The objective of this study was to determine the effects of consuming 42.5 g/day of mixed nuts on LDL-C, Lp(a), and inflammatory markers in individuals with overweight or obesity.Methods and resultsIn a 16-week randomized control trial, 29 participants with overweight or obesity (BMI 25–40 kg/m²) consumed either 42.5 g/day of mixed nuts (cashews, almonds, macadamia nuts, Brazil nuts, pecans, pistachios, walnuts, and peanuts) or 69 g/day isocaloric pretzels. Blood samples were collected at baseline, week 8, and week 16 for analysis on total cholesterol (TC), LDL-C, Lp(a), inflammation markers, glucose, insulin, adiponectin and liver function enzymes. No significant differences were seen in TC, LDL-C, HDL-C, Lp(a), or liver function enzymes between the two groups. Participants consuming mixed nuts had significantly lower body fat percentage and diastolic blood pressure, and higher adiponectin (all P ≤ 0.05). C-reactive protein (CRP) and 8-oxo-deoxyguanosis (8-oxodG) showed non-significant decreasing trends and total antioxidant capacity (TAC) had a non-significant increasing trend in the mixed nut group.ConclusionConsumption of mixed nuts had no evidence of an effect on LDL-C or Lp(a) throughout the intervention. Notably, mixed nut consumption lowered body fat percentage without significant changes in body weight or BMI. Future studies with larger sample sizes investigating the changing trends of CRP, 8-oxodG, and TAC are warranted.Clinical trial registerNCT03375866.     

Incidence,Characterization, and Clinical Impact of Device-Related Thrombus Following Left Atrial Appendage Occlusion in the Prospective Global AMPLATZER Amulet Observational Study

ObjectivesThis study sought to report the incidence, characteristics, and clinical impact of device-related thrombus (DRT) following left atrial appendage occlusion (LAAO) with the AMPLATZER Amulet device (Abbott, Plymouth, Minnesota).BackgroundDRT is a potential serious complication of LAAO, but the incidence and clinical impact of DRTs in a real-world setting are not well characterized.MethodsA total of 1,088 patients were enrolled in a multicenter prospective study and followed for 1 year. All events were adjudicated by an independent committee, including the presence of DRT. Patients with DRT were reviewed for suboptimal device implantation and characterization of DRT formation. Multiple Cox regression was performed to identify predictors of DRT formation.ResultsDevice implantation was successful in 1,078 (99%) patients, with 1-year follow-up completed in 96.3% of patients. A total of 18 DRTs occurred in 17 patients (1.7%/year), as a second DRT developed following complete resolution of an initial DRT in 1 patient. The left upper pulmonary vein ridge was not covered by the Amulet disc in 82% of DRT patients, indicating suboptimal implantation, with most thrombus developing in the untrabeculated area of the LAA ostium between the pulmonary vein ridge and the upper edge of the disc. Three (18%) DRT patients had an ischemic stroke, all within 3 months of DRT diagnosis. Patients with a DRT were at a greater risk for ischemic stroke or transient ischemic attack compared with non-DRT patients (hazard ratio: 5.27; 95% confidence interval: 1.58 to 17.55; p = 0.007). Larger LAA orifice width was a predictor of DRT formation (hazard ratio: 1.09; 95% confidence interval: 1.00 to 1.19; p = 0.04).ConclusionsFollowing LAAO with the AMPLATZER Amulet device, DRT was observed infrequently. Although the presence of DRT was associated with an increased rate of ischemic stroke or transient ischemic attack as compared with patients without DRT, the large majority of DRT patients (82%) did not experience any ischemic neurologic events.     

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

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Native T1 Mapping,Extracellular Volume Mapping,and Late Gadolinium Enhancement in Cardiac Amyloidosis: A Meta-Analysis

ObjectivesThis study aimed to compare the diagnostic and prognostic performance of native T1 mapping (T1), extracellular volume (ECV) mapping, and late gadolinium enhancement (LGE) imaging for evaluating cardiac amyloidosis (CA).BackgroundCA is a progressive infiltrative process in the extracellular space that is often underdiagnosed and holds a poor prognosis. Cardiac magnetic resonance (CMR) offers novel techniques for detecting and quantifying the disease burden of CA.MethodsWe searched PubMed for published studies using native T1, ECV, or LGE to diagnose and prognosticate CA. A total of 18 diagnostic (n = 2,015) and 13 prognostic studies (n = 1,483) were included for analysis. Pooled sensitivities, specificities, diagnostic odds ratios (DORs) of all diagnostic tests were assessed by bivariate analysis. Pooled hazard ratios (HRs) for mortality for the 3 techniques were determined.ResultsBivariate comparison showed that ECV (DOR: 84.6; 95% confidence interval [CI]: 30.3 to 236.2) had a significantly higher DOR for CA than LGE (DOR: 20.1; 95% CI: 9.1 to 44.1; p = 0.03 vs. ECV). There was no significant difference between LGE and native T1 for sensitivity, specificity, and DOR. HR was significantly higher for ECV (HR: 4.27; 95% CI: 2.87 to 6.37) compared with LGE (HR: 2.60; 95% CI: 1.90 to 3.56; p = 0.03 vs. ECV) and native T1 (HR: 2.04; 95% CI: 1.24 to 3.37; p = 0.01 vs. ECV).ConclusionsECV demonstrates a higher diagnostic OR for assessing cardiac amyloid than LGE and a higher HR for adverse events compared with LGE and native T1. In addition, native T1 showed similar sensitivity and specificity as ECV and LGE without requiring contrast material. Although limited by study heterogeneity, this meta-analysis suggests that ECV provides high diagnostic and prognostic utility for the assessment of cardiac amyloidosis.     

Cost Effectiveness of Mailed Outreach Programs for Colorectal Cancer Screening: Analysis of a Pragmatic,Randomized Trial

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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.