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Background: Lipoprotein(a) [Lp(a)] and metabolic syndrome (MetS) are well-established risk factors for cardiovascular disease. Recent evidence suggests that high Lp(a) levels may increase the risk of coronary heart disease (CHD) in patients with diabetes, raising the question of whether similar interactions exist between Lp(a) and metabolic syndrome. We aimed to evaluate the joint association of Lp(a) and MetS with incident CHD risk in a large, multi-ethnic, prospective cohort. Methods: We analyzed 6,664 participants from the MESA (Multiethnic Study of Atherosclerosis) cohort (median follow-up 14.0 years) without baseline CHD. MetS was defined as ≥3 of the following criteria: waist circumference ≥102 cm (men), or ≥88 cm (women), triglycerides ≥150 mg/dL or use of a fibrate medication, HDL-C <40 (men) or <50 (women) or use of a fibrate medication, SBP ≥130 mm Hg and/or DBP ≥85 mm Hg or use of antihypertensive medication, fasting glucose ≥100 mg/dL or use of antidiabetic medication (4). Elevated Lp(a) was defined as a level ≥50 mg/dL. CHD was defined as myocardial infarction, resuscitated cardiac arrest, or CHD death. Participants were divided into four groups: group 1: Normal Lp(a) without MetS, group 2: elevated Lp(a) without MetS, group 3: normal Lp(a) with MetS, group 4: elevated Lp(a) with MetS. Survival analysis using Kaplan-Meier and multivariable Cox proportional hazard models were performed to assess the relationship between Lp(a), MetS, and time to CHD. Results: In an adjusted model, log [Lp(a)] and MetS were both independently associated with CHD (HR: 1.14; 95% CI: 1.03, 1.25) and (HR: 1.75; 95% CI: 1.35, 2.27). Compared to the reference group (normal Lp(a) without MetS), those with elevated Lp(a) without MetS (group 2) did not have increased risk of CHD (HR: 1.30; 95% CI: 0.94, 1.80). However, those with normal Lp(a) with MetS (group 3) had greater risk of CHD (HR: 1.56; 95% CI: 1.18, 2.05). The highest risk for CHD were in those with elevated Lp(a) with MetS (group 4) (HR: 2.37; 95% CI: 1.66, 3.37). Conclusions: In this analysis. elevated Lp(a) and MetS independently increase CHD risk. MetS alone significantly increases risk, whereas elevated Lp(a) without MetS does not demonstrate a significant effect. However, their combination confers the highest risk, suggesting a synergistic interaction. These results emphasize the value of assessing Lp(a) in individuals with MetS to improve cardiovascular risk stratification and guide targeted prevention.

Background: The comparable long-term benefits of coronary artery bypass grafting (CABG) versus percutaneous coronary intervention (PCI) in patients with multivessel disease remains limited in underrepresented populations, particularly in patients with multivessel coronary artery disease and heart failure with severely reduced left ventricular ejection fraction (LVEF <35%). Research Question: Among patients with HF and LVEF < 35% which revascularization strategy (CABG or PCI) provides superior long-term clinical outcomes? Methods: We conducted a systematic review and meta-analysis of observational studies involving patients with ischemic heart disease (IHD), HF and LVEF < 35% undergoing PCI or CABG with a minimum follow-up duration of five years. PubMed, Embase, and Cochrane databases were searched for studies published up to April 15, 2025. We computed hazard ratios (HR) from propensity score matched results. We used Cochrane Review Manager version 9.2.1 for statistical analysis. The primary endpoints of interest included all-cause mortality at 5 to 10 years, repeat revascularization, and all-cause mortality at 10 or more years. Results: We included 8 studies with 12,697 patients (6,187 PCI vs 6,510 CABG). Median follow-up duration ranged from 3.8 to 5.2 years, with the longest reported follow-up up to 13 years. The cumulative, propensity adjusted, incidence of all-cause mortality was significantly lower in the CABG group compared to PCI in 5 to 10 years of follow-up (HR 0.61; 95% CI 0.54-0.69; p<0.001) and ≥ 10 years (HR 0.63; 95% CI 0.53-0.74; p<0.001). Additionally, CABG was associated with a reduced need for repeat revascularization in the 5 to 10 year time frame, with a HR of 0.42 (95% CI 0.22-0.81; p=0.01). Conclusion: In this systematic review and meta-analysis of patients with IHD and an ejection fraction ≤ 35% undergoing revascularization, CABG was associated with a reduction in all-cause mortality at ≥ 5 and ≥ 10 years of follow-up, as compared to PCI.

Problem Statement: The prognostic value of troponin elevation in septic ICU patients without known history of cardiac disease remains unclear, particularly after accounting for overall illness severity. Background: Minor troponin rises are frequent during sepsis, yet clinicians still lack a clear cut-point that signals danger once cardiac disease is ruled out. We asked whether a modest increase in troponin-T predicts in-hospital death beyond global illness severity. Methods: We studied 1 221 adult first ICU stays labelled “sepsis” in the eICU Collaborative Research Database and removed any case with a cardiac admission diagnosis. Implausible or missing laboratory values were imputed by multiple imputation. Hospital mortality was modelled with logistic regression that included troponin (a continuous and a binary model with threshold > 0.04 ng/mL) together with age, sex, lactate, albumin, BUN, creatinine, intubation status, vasopressor use, dialysis requirement and APACHE-IV predicted mortality. A natural-spline model explored non-linear behavior. Findings were checked in a 1:1 propensity-matched cohort. Results: Overall mortality was 11.7%. Troponin exceeded 0.04 ng/mL in 38% of patients. After adjustment for APACHE-IV probability and other covariates, a troponin level > 0.04 ng/mL was associated with almost twice the odds of death (OR ≈ 1.9), whereas the continuous model suggested only a modest trend (OR ≈ 1.1 per ng/mL). The spline curve rose steeply between 0 and 0.10 ng/mL and flattened thereafter, pinpointing an inflection near 0.05 ng/mL. Matching on all measured confounders confirmed that high-troponin patients had about three-fold greater mortality (OR ≈ 2.8, 1.55-5.05; p<0.001), highlighting that even modest troponin elevation is an independent risk marker for death in septic ICU patients. A bedside heat-map combining troponin, albumin and need for intubation illustrated a simple gradient: risk climbs from 2 % in low-troponin, well-albuminised, non-intubated patients to nearly 7 % when troponin exceeds 0.10 ng/mL in intubated, hypo-albuminemic patients. Conclusions: Even modest troponin elevations (> 0.04 ng/mL) independently predict mortality in sepsis after rigorous adjustment and matching on APACHE-IV physiology, lactate, and organ-support variables. This biologic threshold supports incorporating troponin into bedside triage and future septic cardiomyopathy trials.

Introduction: Telomere biology disorders (TBD) are multisystemic accelerated aging syndromes due to abnormal telomere length (TL) shortening and increased cancer risk. Pediatric-onset TBD is characterized by severely shortened TL and specific associations with germline pathogenic variants mainly in DKC1, TINF2, PARN genes and characteristic clinical features [bone marrow failure (BMF), abnormal nail/skin/oral mucosa]. Adult-onset TBD is genetically distinct (predominantly, TERT, TERC, and RTEL1 mutations) with varied organ involvement [interstitial lung disease (ILD), BMF, cirrhosis, or bone disease] and heterogenous outcomes. In our previous study of predominantly adult patients with short telomeres, multiple organ involvement (Mangaonkar A et al. Blood Cancer J 2021) predicted poor overall survival (OS). We sought to validate these findings in a larger, well annotated adult cohort of TBD patients. Methods: Patients with suspected TBD underwent comprehensive clinical and molecular evaluation through our TBD-dedicated clinic after regulatory approval. TL was assessed through clinical flow cytometry fluorescence in-situ hybridization (FlowFISH).Clinical and laboratory features, including pulmonary imaging, lung volumes/function testing, hepatic imaging (MR elastography/fibroscan) and bone density assessments were retrospectively abstracted. Germline and somatic genetic testing was performed on peripheral blood through targeted panels for known TBD and myeloid genes respectively. Cox proportional hazard model was used to identify significant variables that also retained independent prognostic impact. Results: Overall, 122 patients met criteria for TBD as defined by lymphocyte TL (LTL) &lt;=10th percentile and/or a presence of a germline-TBD variant; 34 patients LTL &lt;1st percentile, 84 1st and the 10th percentile (27 with TBD-germline variants) and 4 with only TBD-germline variants. Median age at diagnosis was 56 (18-77) years, with 72 (59%) males. Clinical features included presence of ILD (n=81, 66%), BMF (n=39, 32%), cirrhosis/hepatic fibrosis (n=19, 38%), bone disease osteopenia/osteoporosis/fractures, n=53, 70%), MDS/AML (n=11, 9%), non-hematological cancer (n=38, 31%), and head and neck cancer (n=2). Germline pathogenic variants were detected in 22 (18%), most frequently in TERT (n=10), RTEL1 (n=7) and TERC (n=2), while variants of uncertain significance (VUS) were seen in 35 (29%) patients, especially in TERT (n=20), TERC/RTEL1(n=6), NAF1 (n=4). Somatic variants in hematopoietic cells were detected in 37 (30%) patients with frequent alterations seen in DNA damage response and repair (PPM1D/TP53, n=11), and splicing component (U2AF1/SF3B1/ZRSR2, n=9) genes. At last follow-up [median of 3 (0-18) years], there were 26 (21%) deaths (most commonly, progressive ILD-18, cancer of lung/breast/pancreas-3, transplant-related complications-2). After censoring patients at the time of any transplantation (lung transplant-26, liver transplant-5, bone marrow transplant-8), the Kaplan-Meier estimate of median OS was not reached. Univariate survival analysis found adverse OS predicted by older age at diagnosis (P=0.006), presence of ILD (P=0.0002), hepatic fibrosis/cirrhosis (P=0.02), and somatic DNA repair variants (P=0.03). Multivariate model analysis found that only presence of ILD retained independent prognostic impact (HR=2, P=0.02). Among radiographic ILD subtypes, UIP was the most common (51%), followed by NSIP (10%), and others (6%), with median FEV1 of 2L (range: 0.5-4.6), FVC 2.4L (0.7-6.2), and TLC 4L (1.9-7.4). TBD-ILD patients were older (P&lt;0.0001) with a male preponderance (P=0.03), 52 (64%) with multi-organ involvement, and had a less severe hematological phenotype [lower incidence of BMF (P&lt;0.0001) and fetal hemoglobin elevation (P=0.01)], more frequent bone disease (P=0.0009), relatively longer telomeres in lymphocytes (P=0.04), and no particular association with any germline or somatic genetic alterations. Conclusions: Presence of ILD is an independent and significant predictor of adverse survival in adult TBD. Within adult TBD, patients with ILD represent a unique clinical subtype without any obvious genetic or pathologic correlates. Focusing on definitive therapeutic measures in this subgroup of adult TBD has the best chance to alter natural history and improve outcomes.

Abstract Objective The presence of comorbidities can substantially affect patients’ quality of life, but data regarding their impact on idiopathic inflammatory myopathies (IIMs) are limited. Methods We examined the prevalence of comorbidities in IIM patients, other autoimmune rheumatic diseases (oAIRDs) and healthy controls (HCs), using data from the self-reported COVAD-2 survey. We defined basic multimorbidity (BM) as the presence of ≥2 non-rheumatic chronic conditions and complex multimorbidity (CM) as the presence of ≥3 non-rheumatic chronic conditions affecting ≥3 organ systems. Hierarchical clustering on principal components was performed for grouping. Results Among the COVAD respondents, 1558 IIMs, 4591 oAIRDs and 3652 HCs were analysed. IIMs exhibited a high burden of comorbidities (odds ratio [OR]: 1.62 vs oAIRDs and 2.95 vs HCs, P &lt; 0.01), BM (OR: 1.66 vs oAIRDs and 3.52 vs HCs, P &lt; 0.01), CM (OR: 1.69 vs AIRDs and 6.23 vs HCs, P &lt; 0.01) and mental health disorders (MHDs) (OR: 1.33 vs oAIRDs and 2.63 vs HCs, P &lt; 0.01). Among the IIM patients, those with comorbidities or MHDs had lower PROMIS Global Physical (PGP), PROMIS Global Mental (PGM), and PROMIS Physical Function (SF10) scores, and higher fatigue (F4a) scores (all P &lt; 0.001). PGP, PGM, SF10a and F4a were influenced by age, active disease, BM and MHDs. Four distinct clusters were identified among the IIMs according to comorbidities and PROMIS scores. Conclusion Patients with IIMs have a higher burden of comorbidities that influence physical and mental health, identifiable as clinical clusters for optimized and holistic management approaches.

AbstractObjectiveThe first international consensus criteria for optic neuritis (ICON) were published in 2022. We applied these criteria to a prospective, global observational study of acute optic neuritis (ON).MethodsWe included 160 patients with a first‐ever acute ON suggestive of a demyelinating CNS disease from the Acute Optic Neuritis Network (ACON). We applied the 2022 ICON to all participants and subsequently adjusted the ICON by replacing a missing relative afferent pupillary defect (RAPD) or dyschromatopsia if magnetic resonance imaging pathology of the optical nerve plus optical coherence tomography abnormalities or certain biomarkers are present.ResultsAccording to the 2022 ICON, 80 (50%) patients were classified as definite ON, 12 (7%) patients were classified as possible ON, and 68 (43%) as not ON (NON). The main reasons for classification as NON were absent RAPD (52 patients, 76%) or dyschromatopsia (49 patients, 72%). Distribution of underlying ON etiologies was as follows: 78 (49%) patients had a single isolated ON, 41 (26%) patients were diagnosed with multiple sclerosis, 25 (16%) patients with myelin oligodendrocyte glycoprotein antibody‐associated disease, and 15 (9%) with neuromyelitis optica spectrum disorder. The application of the adjusted ON criteria yielded a higher proportion of patients classified as ON (126 patients, 79%).InterpretationAccording to the 2022 ICON, almost half of the included patients in ACON did not fulfill the requirements for classification of definite or possible ON, particularly due to missing RAPD and dyschromatopsia. Thorough RAPD examination and formal color vision testing are critical to the application of the 2022 ICON.

Abstract Innovation in medical imaging artificial intelligence (AI)/machine learning (ML) demands extensive data collection, algorithmic advancements, and rigorous performance assessments encompassing aspects such as generalizability, uncertainty, bias, fairness, trustworthiness, and interpretability. Achieving widespread integration of AI/ML algorithms into diverse clinical tasks will demand a steadfast commitment to overcoming issues in model design, development, and performance assessment. The complexities of AI/ML clinical translation present substantial challenges, requiring engagement with relevant stakeholders, assessment of cost-effectiveness for user and patient benefit, timely dissemination of information relevant to robust functioning throughout the AI/ML lifecycle, consideration of regulatory compliance, and feedback loops for real-world performance evidence. This commentary addresses several hurdles for the development and adoption of AI/ML technologies in medical imaging. Comprehensive attention to these underlying and often subtle factors is critical not only for tackling the challenges but also for exploring novel opportunities for the advancement of AI in radiology.

Abstract The adoption of artificial intelligence (AI) tools in medicine poses challenges to existing clinical workflows. This commentary discusses the necessity of context-specific quality assurance (QA), emphasizing the need for robust QA measures with quality control (QC) procedures that encompass (1) acceptance testing (AT) before clinical use, (2) continuous QC monitoring, and (3) adequate user training. The discussion also covers essential components of AT and QA, illustrated with real-world examples. We also highlight what we see as the shared responsibility of manufacturers or vendors, regulators, healthcare systems, medical physicists, and clinicians to enact appropriate testing and oversight to ensure a safe and equitable transformation of medicine through AI.

Abstract Objectives The objective of this study was to explore the prevalence, characteristics and risk factors of COVID-19 breakthrough infections (BIs) in idiopathic inflammatory myopathies (IIMs) using data from the COVID-19 Vaccination in Autoimmune Diseases (COVAD) study. Methods A validated patient self-reporting e-survey was circulated by the COVAD study group to collect data on COVID-19 infection and vaccination in 2022. BIs were defined as COVID-19 occurring ≥14 days after two vaccine doses. We compared BI characteristics and severity among patients with IIMs, patients with other autoimmune rheumatic and non-rheumatic diseases (AIRD, nrAID), and healthy controls (HCs). Multivariable Cox regression models were used to assess the risk factors for BI, severe BI ,and hospitalizations among patients with IIMs. Results Among the 9449 included responses, BIs occurred in 1447 respondents (15.3%). The median age was 44 years [interquartile range (IQR) 21], 77.4% were female, and 182 BIs (12.9%) occurred among the 1406 patients with IIMs. Multivariable Cox regression among the data for patients with IIMs showed increasing age to be a protective factor for BIs [hazard ratio (HR) = 0.98, 95% CI = 0.97–0.99], and HCQ and SSZ use were risk factors (HR = 1.81, 95% CI = 1.24–2.64, and HR = 3.79, 95% CI = 1.69–8.42, respectively). Glucocorticoid use was a risk factor for a severe BI (HR = 3.61, 95% CI = 1.09–11.8). Non-white ethnicity (HR = 2.61, 95% CI = 1.03–6.59) was a risk factor for hospitalization. Compared with other groups, patients with IIMs required more supplemental oxygen therapy (IIMs = 6.0% vs AIRDs = 1.8%, nrAIDs = 2.2% and HCs = 0.9%), intensive care unit admission (IIMs = 2.2% vs AIRDs = 0.6%, nrAIDs and HCs = 0%), advanced treatment with antiviral or monoclonal antibodies (IIMs = 34.1% vs AIRDs = 25.8%, nrAIDs = 14.6% and HCs = 12.8%) and had more hospitalization (IIMs = 7.7% vs AIRDs = 4.6%, nrAIDs = 1.1% and HCs = 1.5%). Conclusion Patients with IIMs are susceptible to severe COVID-19 BIs. Age and immunosuppressive treatments were related to the risk of BIs.