Citations

Abstract Introduction Revascularization to prevent limb loss is not feasible or represents a very high risk in a significant proportion of patients with chronic limb-threatening ischaemia (CLTI). No standard definition currently exists to define this population of patients. The aim of this study was to develop a consensus-based, multidomain definition to improve clinical assessment and reporting of studies in people with ‘no option’ (NO) or ‘poor option’ (PO) CLTI. Methods A modified Delphi process was conducted with 164 specialists from 30 countries. Two iterative survey rounds were used to reach consensus, defined as ≥70% agreement with a score of ≥7 on a nine-point scale. Results Some 164 international vascular specialists participated in the study, averaging 19 years of experience. A multidomain framework including arterial disease anatomy, biology, risk, function, and context (ABRFC) achieved 83% consensus. A ‘desert foot’ was defined as the absence of distal arterial revascularization targets on advanced non-invasive imaging, invasive digital subtraction angiography, and at least one failed endovascular revascularization attempt (81.6% agreement). Inadequate autogenous bypass conduit was defined as the lack of usable autologous vein across all four limbs (85% agreement). Patients were classified as NO for revascularization if they present with ‘desert foot’, prohibitive medical risk, a non-functional limb, or in those patients who refused arterial revascularization. PO revascularization patients combined factors such as severe infection, lack of autologous vein, or treatment non-compliance (72.1% agreement). Conclusion This consensus study established a structured, expert-validated definition of no option or poor option for revascularisation of patients with CLTI. The multidomain ABRFC framework provides a foundation for standardized clinical assessment, trial design, and future guideline development.

Abstract Background Measurement of cardiac troponin (cTn) using high-sensitivity assays is recommended for the diagnosis of myocardial infarction. We determined sex-specific and uniform 99th percentile upper reference limits (URLs) using the new Elecsys® Troponin T high-sensitivity Gen 6 assay in a global, healthy reference range cohort. Methods Lithium-heparin plasma and serum samples were prospectively collected from apparently healthy individuals aged ≥20 years across 34 global sites in the United States, Europe, China, and Japan. cTnT was measured using the Troponin T high-sensitivity Gen 6 assay on the Cobas® e 801 analyzer. Exclusion criteria were defined according to the 2022 IFCC guidance. Uniform and sex-specific 99th percentile URLs and nonparametric 95% CIs were determined in plasma and serum separately and combined. Results The final study population comprised 4147 participants (52.5% female) with a median (25th–75th percentiles) age of 48.0 (33.0–59.0) years; 45.8%, 47.9%, 5.2%, and 1.1% were White, Asian, Black, and other/unknown, respectively. For sample matrices combined (n = 8294), 81.0% and 99.2% of cTnT values were above the limit of detection in females and males, respectively. Sex-specific 99th percentile URLs (95% CI) were 18 (16–23) ng/L for females and 32 (28–35) ng/L for males; the uniform 99th percentile URL was 27 (24–31) ng/L. URLs were comparable in plasma and serum samples. Conclusions This study determined sex-specific and uniform 99th percentile URLs for the Troponin T high-sensitivity Gen 6 assay that were comparable irrespective of the matrix used in a large, global, healthy reference population.

AbstractBackgroundInfants born via Cesarean section (C‐section) often have a distinct gut microbiome and higher risks of atopic and immune‐related conditions than vaginally delivered infants. We evaluated whether a microbiome‐based program could shift gut microbiome composition and improve microbiome‐associated health outcomes in C‐section born infants.MethodsThis open‐label, randomized, controlled trial included full‐term C‐section‐born infants aged 0–3 months, randomized to an intervention (n = 25) or control arm (n = 29). Over 6 months, the intervention arm received two microbiome reports, personalized recommendations based on their microbiome, educational materials, and coaching calls focused on microbiome health. Parents reported health conditions via surveys. Primary outcome: Difference between study arms in relative abundance of key gut microbiome taxa and functional genes. Other outcomes: Changes in a C‐section index—a taxonomy‐based metric comparing C‐section‐associated taxa to vaginally‐associated taxa—and prevalence of atopic conditions.ResultsCompared to controls, the intervention arm had higher Bifidobacterium (p = .025, q = .121) and higher abundance of genes associated with human milk oligosaccharide degradation (e.g., α‐L‐fucosidase, p = .019, q = .046) at timepoint 2. In the intervention arm, the C‐section index decreased to a level similar to vaginally born infants (p = .807, q = .807). At the end of the intervention, atopic dermatitis prevalence was lower in the intervention arm than in controls (odds ratio, 0.17 [95% CI, 0.023–0.723], p = .031).ConclusionA personalized microbiome‐based program can modulate the gut microbiome of C‐section‐born infants and may reduce the risk of atopic conditions (ClinicalTrials.gov: NCT06424691).

Background— Previously published evidence on ischemic mitral regurgitation (IMR) and its adverse prognosis after myocardial infarction has been based on the severity of IMR in the subacute or chronic period of myocardial infarction. However, the state of IMR can vary from the early stage to the chronic stage as a result of various responses of myocardium after primary percutaneous coronary intervention (PCI). Methods and Results— Standard echocardiography was serially performed in 546 consecutive patients with first-onset acute myocardial infarction (1) immediately after their arrival (pre-PCI), (2) before discharge (early post-PCI), and (3) 6 to 8 months after PCI (late post-PCI). The course of IMR after primary PCI and the prognostic impact of the IMR in each phase were investigated. IMR was found in 193/546 (35%) patients at the emergency room. In the acute phase after PCI, IMR improved in 63 patients. IMR worsened in 78 patients despite successful PCI. Shorter onset-to-reperfusion time and nontotal occlusion before PCI were the independent predictors of early improvement of IMR. In the chronic phase, IMR improved in 79 patients and worsened in 36 patients. Lower peak creatine kinase–myocardial band was an independent predictor of late improvement of IMR. IMR before PCI worsened 30-day prognosis ( P =0.02), and persistent IMR in the chronic phase worsened long-term prognosis ( P =0.04) after primary PCI. Conclusions— Degrees of IMR changed in the early and chronic phase after primary PCI for acute myocardial infarction. IMR on arrival and persistent IMR in the chronic phase worsened short-term and long-term prognosis after acute myocardial infarction, respectively.