Temporal meal patterns are suggested to influence cardiometabolic health, but existing evidence is limited, inconclusive, and largely cross-sectional. This study aimed to examine associations between temporal meal patterns and cardiovascular risk factors, and whether meal timing is associated with incident cardiovascular disease (CVD).

The study included 3812 participants (18-75 years) in the Malmö Offspring Study who completed 4-day web-based dietary records and provided fasting blood samples. Cross-sectional analyses assessed associations between temporal meal patterns and risk factors, while a nested case-control study evaluated associations with incident CVD.

Meal frequency was nonlinearly associated with HDL-cholesterol, with the highest HDL levels observed at 4.7 meals/day. Each additional eating occasion was associated with 15% lower odds of metabolic syndrome (MS). Breakfast skipping was associated with higher total cholesterol (0.12 mmol/L 95% CI: 0.04, 0.21) and, among men, higher LDL-cholesterol (0.15 mmol/L 95% CI: 0.03, 0.26) but not with MS. Each additional hour of the eating window was associated with lower total and LDL-cholesterol (- 0.03 mmol/L 95% CI: - 0.05, - 0.01, and - 0.04, - 0.01) and a 7% (95% CI: 0.88, 0.98) reduction in odds of MS. A later first meal of the day, was associated with higher odds of MS (9% per hour, 95% CI: 1.01, 1.16). Prospectively, a later energy midpoint was associated with 31% higher odds of CVD (95% CI: 1.00, 1.74).

Starting to eat early in the day, regular breakfast consumption, an earlier energy midpoint, higher meal frequency, and a longer eating window may be associated with favourable cardiometabolic health.

Cardiovascular-kidney-metabolic (CKM) syndrome represents an integrated continuum of metabolic, kidney, and cardiovascular abnormalities. However, the stage-specific metabolic heterogeneity underlying this clinical framework remains incompletely characterised.

We performed plasma metabolomic profiling in 1374 participants from the China Multi-Ethnic Cohort across CKM stages 0-4. Participants from Chengdu and Chongqing provinces comprised the discovery cohort (n = 969), whereas those from Yunnan province comprised the validation cohort (n = 405). Stage-associated metabolites were identified using prespecified pairwise comparisons with OPLS-DA and covariate-adjusted limma analyses. Weighted correlation network analysis identified coordinated metabolic modules. Machine-learning models were developed to evaluate discrimination of advanced CKM (stages 3-4) using metabolite signatures independent of conventional CKM-defining variables.

Among 858 endogenous metabolites, 261 unique metabolites were associated with CKM stages, revealing distinct metabolic patterns from early to advanced CKM. Stage 1 was characterised by altered lipid- and bile acid-related metabolites, stage 2 by broader lipid and amino-acid remodelling, and stage 3 by additional carbohydrate, aromatic amino-acid, secondary bile acid, host-microbial, and renal-handling signals. Metabolic separation between stages 3 and 4 was comparatively weak. WGCNA identified a CKM-associated turquoise module, with γ-glutamylvaline as a hub metabolite. A model incorporating age, sex, and eight metabolites derived from the discovery cohort showed favourable performance for distinguishing advanced CKM from earlier stages and achieved an AUROC of 0.874 (95% CI, 0.802-0.931) in the validation cohort.

CKM stages exhibit distinct and non-linear metabolic signatures. A compact metabolomic panel independent of conventional CKM-defining variables may provide complementary molecular information for advanced CKM phenotyping and future risk stratification.

Coronary bifurcation lesions (CBLs) account for approximately 15%-20% of all percutaneous coronary interventions and remain a therapeutic challenge. A hybrid strategy combining drug-coated balloons (DCBs) for the side branch with drug-eluting stents (DESs) for the main vessel has emerged as a novel therapy aimed at mitigating complications associated with permanent implants. This study was aimed at systematically evaluating the efficacy and safety of the hybrid strategy compared with a DES-only strategy (including single- and double-stent strategies) in CBLs.

Following the PRISMA 2020 guidelines, we systematically searched major databases for randomized controlled trials (RCTs) and observational studies comparing the DES + DCB hybrid strategy with a DES-only strategy for CBLs. The primary endpoint was major adverse cardiovascular events (MACE). Secondary endpoints included target lesion revascularization (TLR), target vessel revascularization (TVR), late lumen loss (LLL), myocardial infarction (MI), and restenosis rate. Statistical analyses were performed using RevMan 5.4 and StataMP.

We included 13 studies, comprising five RCTs and eight observational studies, with a total of 2186 patients (1030 in the hybrid strategy group and 1156 in the DES-only group). Compared with the DES-only strategy, the hybrid strategy was associated with a lower incidence of MACE (OR 0.75; 95% CI 0.57-0.99; p = 0.04) and a lower risk of TLR (OR 0.46; 95% CI 0.26-0.79; p = 0.005); however, the MACE benefit was of borderline statistical significance. Regarding angiographic endpoints, the hybrid strategy substantially lowered the risk of side branch restenosis (OR 0.13; 95% CI 0.05-0.34; p < 0.0001). Side branch LLL was consistently lower with the hybrid strategy across all contributing studies; however, extreme between-study heterogeneity (I² = 96%) precluded meaningful pooling. Subgroup analysis indicated a more pronounced reduction in MACE risk for left main lesions (OR 0.50; 95% CI 0.31-0.81; p = 0.005), with extremely low heterogeneity (I² = 0%). No statistically significant differences were observed between the two groups with respect to MI or TVR.

For CBLs, the DES + DCB hybrid strategy appears to offer favorable safety and efficacy compared with a stent-only strategy. The observed benefits likely reflect both the avoidance of a second permanent stent implant and the localized antiproliferative drug delivery by the DCB, collectively reducing side branch restenosis and TLR. These findings support the hybrid approach as a promising alternative to complex double-stent techniques, although large-scale RCTs are warranted to confirm these results.

Nephrectomy in pediatric kidney transplantation is still practiced routinely at some institutions. Despite this, the clinical utility of nephrectomy for certain indications such as proteinuria and hypertension on pre- and post-transplant outcomes is unknown.

All children who underwent kidney transplant and native nephrectomy between 2009 and 2025 were reviewed for baseline clinical covariates, operative details, and outcomes.

Of the study population, 70 patients underwent unilateral nephrectomy and 61 underwent bilateral nephrectomy. The median age at transplant in the unilateral nephrectomy group was 12.5 years [9.3, 15.9] vs. 10.7 [7.1, 14.1] in the bilateral nephrectomy group. Operative time was 351.5 [294.8, 413.8] minutes vs. 353 [292, 420], median hospital length of stay 8 days [7, 11] vs. 11 days [8, 16], complications 8 (11%) vs. 15 (25%), and post-transplant delayed graft function 4 patients (6%) vs. 7 (12%). Rejection occurred in 1 patient per group. In the 18 patients who had a nephrectomy for proteinuria, the change in albumin was similar between groups (0.4 g/dL [-0.1, 0.4] vs. 0 g/dL [-0.2, 0.2]). In the 23 patients who had a nephrectomy for hypertension, the change in antihypertensive medications after transplant was higher in the unilateral nephrectomy group (1.5 medications less [0.8, 2] vs. 0 [0, 1]).

For the indications of proteinuria and hypertension, clinical outcomes were similar between bilateral vs. unilateral nephrectomy for individuals who underwent kidney transplantation. These findings support consideration of pursuing fewer bilateral native nephrectomies in these patient populations.

  BACKGROUND: Large disparities in treatments and outcomes of ST-elevation myocardial infarction (STEMI) patients driven by insurance status have been reported. However, it is unknown whether this applies to Switzerland, a country characterised by an overall high income, mandatory basic health insurance covering virtually all treatments and the option of a supplementary private health insurance allowing for full institution and doctor choice as well as a higher service standard. This study aimed to assess the impact of insurance status on treatments and outcomes in STEMI patients in Switzerland.

STEMI patients enrolled in the nationwide Acute Myocardial Infarction in Switzerland (AMIS) Plus registry between 2005 and 2023 were analysed. We compared patients with basic health insurance only to those with supplementary private health insurance with respect to optimal medical therapy, percutaneous coronary intervention (PCI) and outcomes. Primary outcome measures were rates of optimal medical therapy and full guideline-recommended treatment (FGRT) (defined as optimal medical therapy plus PCI). Secondary outcome measures were in-hospital all-cause mortality, major adverse cardiac and cerebrovascular events (MACCE), length of stay and 1-year all-cause mortality after discharge. Multivariate logistic mixed-effects models examined whether insurance type influenced treatments and outcomes.

Among 16,463 patients, 13,023 (79.1%) had only basic health insurance. Patients with basic health insurance only were younger, more often males and had higher rates of obesity, diabetes and active smoking, but lower rates of cancer than supplementary private health insurance patients. In addition, they more often received optimal medical therapy and FGRT. Patients with basic health insurance only had higher rates of in-hospital mortality and MACCE. However, after adjusting for covariates, no statistically significant associations were identified between insurance type and access to optimal medical therapy or FGRT, in-hospital mortality, MACCE, length of stay or 1-year mortality after discharge.

In this study, we observed no significant association between insurance status and treatments or outcomes of STEMI patients, suggesting a high level of equity in acute cardiac care in Switzerland.

Immunotherapy has shown promising efficacy in esophageal squamous cell carcinoma (ESCC), yet its clinical benefits remain limited due to immune evasion. Lactate accumulation in the tumor microenvironment has been found to facilitate immune evasion through protein lactylation. However, the key lactylated substrates and mechanisms driving immune evasion remain undefined. Here, we show that HSPA1A lactylation at lysine 108 (K108) by KAT5 drives CD8⁺ T cell dysfunction and immunotherapy resistance via the STAT1/PD-L1 axis in ESCC. Mechanistically, K108 lactylation enhances HSPA1A binding to STAT1, protecting STAT1 from TRIM25-mediated ubiquitination and proteasomal degradation. This stabilization promotes STAT1 phosphorylation and nuclear translocation, leading to transcriptional upregulation of PD-L1 and subsequent immune evasion. Collectively, these findings highlight the pivotal role of HSPA1A lactylation in facilitating immune evasion via the STAT1/PD-L1 axis, suggesting a potential target for improving immunotherapy efficacy in ESCC.

Mutations in RNA splicing factor PQBP1 cause Renpenning syndrome (RS), yet whether LINE-1 (L1) contributes to RS pathogenesis remains unclear. Here, we generated human forebrain organoids model carrying a novel patient-derived PQBP1 variant (c.28 C > G; p.R10G), and observed impaired neurogenesis in RS organoids. Bulk and single-cell RNA-sequencing revealed that PQBP1 R10G mutation upregulated evolutionarily ancient L1 expression and induced aberrant L1 splicing, resulting in the redundant production of non-canonical L1-containing transcripts. Mechanistically, disrupted PQBP1-HNRNPU interaction by PQBP1 R10G mutation impaired U1/U2 small nuclear ribonucleoprotein (snRNP) recruitment to splicing sites, leading to increased L1-containing intron retention of neurodevelopmental genes, including WDR11. L1 retention reduced canonical WDR11 transcripts and consequently protein expression. Canonical WDR11, not L1-containing isoform, ameliorated the neurodevelopmental deficits of RS organoids. Together, our findings establish the dysregulated PQBP1-HNRNPU-L1 axis as a pathogenic driver of RS and nominate WDR11 as a potential therapeutic target for RS.

In the medical field, such as oncology and cardiovascular diseases, biomarker discovery and development for clinical research, diagnostics, and therapy monitoring in clinical trials have advanced quickly. This has facilitated the development of biomarker-guided, precision-medicine-based targeted therapies and helped in quick and early detection. Cerebrospinal fluid and PET indicators of tau and amyloid-β proteins are among the biomarker discovery and validation advances in Alzheimer's disease (AD). They have shown remarkable accuracy in identifying the presence of pathophysiological and neuropathological alterations linked to AD. However, these assays' high cost, lack of accessibility, and/or invasiveness restrict their applicability as practical first-line methods for identifying pathophysiological patterns. However, the concentrations of brain-derived chemicals in blood are significantly lower than those in CSF, which presents an analytical problem. Blood, as a biofluid to evaluate biomarkers for diseases of the central nervous system, has further problems. However, there has been a significant advancement in recent years. The current status of research on blood biomarkers for AD and associated neurodegenerative dementias is updated in this chapter.

Takayasu arteritis (TA) is a rare large-vessel granulomatous vasculitis predominantly affecting young women. We report the case of a male patient in his early 20s presenting with a three-month history of pyrexia of unknown origin (PUO), significant weight loss, a left carotid bruit and massive splenomegaly, culminating in a diagnosis of Type V TA. The presentation was atypical in several respects: prolonged high-grade fever, marked splenomegaly and male sex are all uncommon in TA.CT angiography demonstrated concentric mural thickening with stenotic involvement of the aorta and its major branches. In conjunction with markedly elevated inflammatory markers, a diagnosis of Type V TA was established. The patient became apyrexial with resolution of constitutional symptoms following initiation of immunosuppressive therapy. This case highlights the imperative to consider TA in atypical clinical contexts, including male sex, PUO and massive splenomegaly. It underscores the value of systematic vascular evaluation in unexplained chronic pyrexia.