Among older patients hospitalized for heart failure, height-indexed appendicular skeletal muscle mass, but not BMI-indexed appendicular skeletal muscle mass, was associated with higher 2-year mortality. Height-indexed ASMM may therefore be the more clinically useful marker for post-discharge risk stratification.

Osteosarcopenia, the co-existence of osteoporosis and sarcopenia, is described as a geriatric syndrome arising from shared determinants of muscle and bone. We asked how far the prevalence of sarcopenia and osteosarcopenia depends on the definition of low muscle mass, whether osteoporosis and sarcopenia co-occur more often than expected under statistical independence, and whether the muscle-bone relationship is expressed in areal bone mineral density (BMD) or in femoral geometry. Cross-sectional study of 649 community-dwelling adults aged 65 years and over (72% women; mean age 71.5 years; mean body mass index (BMI) 29.6 kg/m2) assessed with dual-energy X-ray absorptiometry (GE Lunar iDXA), grip dynamometry (Jamar Hydraulic Hand Dynamometer) and the Short Physical Performance Battery. Osteoporosis followed World Health Organization criteria. Sarcopenia was classified according to EWGSOP2, and low muscle mass was defined three ways (appendicular lean mass (ALM)/height2; absolute ALM; and the Foundation for the National Institutes of Health (FNIH) ALM/BMI index). Observed co-occurrence was compared with the value expected under independence (Fisher exact test, odds ratios (OR) with 95% confidence intervals (CI)); for the best-powered analysis the two one-sided tests (TOST) equivalence procedure using pragmatic equivalence bounds of OR 0.5 to 2.0. Hip structural analysis provided section modulus and cross-sectional area. Low muscle mass ranged from 3.7 to 15.7%, and confirmed sarcopenia from 1.4 to 4.2%, according to the metric. Osteoporosis prevalence was 17.6% (95% CI 14.9 to 20.8). Under none of the sarcopenia definitions was there statistically significant evidence of excess co-occurrence (Fisher p = 0.50 to 1.00), although observed overlap under the absolute-ALM definition was slightly above the independence expectation. For probable sarcopenia (low grip strength), the best-powered comparison, the OR was 0.89 (95% CI 0.47 to 1.67) and equivalence within broad OR bounds of 0.5 to 2.0 was supported (90% CI 0.52 to 1.51; TOST p = 0.037); equivalence was not supported under narrower bounds. Appendicular lean mass was not associated with areal BMD after adjustment for body size (femoral neck standardised β = 0.03, 95% CI - 0.18 to 0.24) but was associated with femoral section modulus substantially more strongly in men than women (globally standardised interaction Δβ = 0.30, 95% CI 0.15 to 0.44, p < 0.001). In this community sample, there was no statistically significant evidence that osteoporosis and sarcopenia co-occurred more often than expected under statistical independence, across several sarcopenia definitions, although estimates for confirmed sarcopenia were imprecise. The muscle-bone association was more apparent for femoral geometry than areal BMD and was seen predominantly in men. These findings do not support assuming that low bone mass and low muscle mass identify the same individuals, but they concern statistical co-occurrence and do not establish biological independence.

Sarcopenia-related traits may be associated with infection-related disease liabilities, but broad phenome-wide genetic screening remains limited. We conducted a two-sample MR-PheWAS of more than 2000 FinnGen R12 phenome-wide endpoints against appendicular lean mass (ALM) and left-hand grip strength (HGS). Multiple testing was controlled using Benjamini-Hochberg false discovery rate (BH-FDR) correction applied separately to 2317 ALM and 2307 HGS primary-estimator tests. Twenty-one ALM endpoints and two HGS endpoints were FDR-significant; the two HGS endpoints were height and weight quantitative traits, and no disease phenotype or infection-related phenotype was FDR-significant for HGS. Among the FDR-significant ALM endpoints, four were infection-related. Rickettsioses were supported by a single instrument and were reported separately, whereas three multi-instrument phenotypes were prioritized for detailed follow-up: postzoster neuralgia, tonsillitis, and sequelae of tuberculosis. On the normalized ALM scale, postzoster neuralgia was associated with higher ALM (IVW beta = 0.01217, P = 1.17 × 10^-4), whereas tonsillitis (beta = -0.02580, P = 1.91 × 10^-4) and sequelae of tuberculosis (beta = -0.01247, P = 2.15 × 10^-4) were associated with lower ALM. Candidate-specific HGS analyses and reverse MR did not show statistically significant associations for these three phenotypes. An exploratory ALM-HGS intersection identified 23 nominally associated disease phenotypes, including five infection-related phenotypes. Exploratory proteomic analyses identified candidate proteins and pathways but did not establish mediation. Overall, the findings indicate phenotype-specific heterogeneity in genetic associations with muscle-related traits and require independent replication.

Pathologic fracture is a complication of bone cancer with probable increased risk following radiation therapy (RT). Low-dose-rate (LDR) RT can spare late-responding normal tissues by allowing intrafraction DNA repair, which could also impact tumor response. This retrospective cohort study evaluated efficacy and fracture rate in canine patients (n = 184) with confirmed or suspected appendicular osteosarcoma that received 10 Gy × 2 palliative RT on consecutive days with LDR (cobalt-60) or standard-dose-rate (SDR, linear accelerator). The overall fracture rate was 21.7%. Patients treated with SDR (600 cGy/min, n = 46) and LDR (range 21.9-83.29 cGy/min, n = 152) did not differ in pathologic fracture rates (22.4% vs. 17.4%, respectively, p = 0.54) or median survival times (231 vs. 248.5 days, respectively, p = 0.448). Pathologic fracture rates did not differ on the basis of weight (<35, 35-50, and >50 kg) or location (24% forelegs, 18% hindlegs, p = 0.44). However, no dog (n = 7) weighing less than 20 kg developed a fracture. Radiographs prior to RT were subjectively assessed for bone integrity. Dogs with predominantly lytic lesions did not have a significantly higher pathologic fracture rate (21.2%-31.69% lytic/mixed vs. 10%-12.5% proliferative, p = 0.054), suggesting that pretreatment radiographic appearance does not reflect fracture risk. Additionally, the presence of a pretreatment cortical bone defect was not associated with eventual fracture (p = 0.7). Adjunctive chemotherapy improved survival time significantly (p = 0.01). On the basis of our data, it is reasonable to compare response rates and survival outcomes in published studies using cobalt irradiation with reports using linear accelerators.

Background and Objectives: Sarcopenia is common among patients receiving maintenance hemodialysis, although prevalence estimates vary according to the diagnostic approach. We assessed sarcopenia defined according to the revised European Working Group on Sarcopenia in Older People (EWGSOP2) criteria, its baseline correlates, and its association with 24-month all-cause mortality. Materials and Methods: In this single-center prospective cohort at a tertiary nephrology center, 176 patients enrolled in December 2022 were followed for 24 months. Confirmed sarcopenia required both low handgrip strength and a low appendicular skeletal muscle index assessed by bioelectrical impedance. Physical performance was not assessed. Because the proportional-hazards assumption was not satisfied, restricted mean survival time (RMST) was used as the primary measure of the survival difference. Results: Sarcopenia was present in 46 of 176 participants (26.1%, 95% CI 20.2-33.1). Older age, lower serum albumin and phosphorus concentrations, lower Kt/V, and longer time on maintenance hemodialysis were independently associated with sarcopenia. Thirty-one participants died during follow-up, and survival was lower among those with sarcopenia (log-rank p = 0.035). The adjusted RMST difference was -3.88 months (95% CI -6.49 to -1.28; p = 0.003). A Cox sensitivity analysis yielded a hazard ratio of 2.62 (95% CI 1.06-6.45). There was no evidence of a sarcopenia-by-sex interaction in the adjusted RMST analysis (p = 0.964). Conclusions: Confirmed sarcopenia was present in approximately one quarter of patients and was associated with approximately four months shorter restricted mean survival over 24 months. EWGSOP2-based assessment may provide prognostic information in this setting; whether routine screening or management based on sarcopenia status improves clinical outcomes remains to be determined.

Background/Objectives: Appendicular lean mass (ALM), alanine aminotransferase (ALT), and type 2 diabetes (T2D) may be genetically linked. However, the ALT-related pathway and shared signals at the SERPINA1 candidate locus remain uncertain. We used Mendelian randomization (MR) to evaluate associations among ALM, ALT, and T2D and compared candidate-locus signals across datasets. ALM represented muscle mass, not clinical sarcopenia. Methods: Using European-ancestry GWAS summary statistics, we performed six bidirectional two-sample MR analyses, multivariable MR (MVMR) with finite-sample t-based inference, and exploratory path-specific two-step MR. FinnGen R12 provided the T2D outcome data for MR and pathway analyses. Pathway analyses used 5000 shared-sampling bootstrap replicates to assess uncertainty in path estimates. We combined locus-level coloc/ABF with signal-specific SuSiE-coloc in the GRCh37 SERPINA1 region. T2DGGI was used only for colocalization. Molecular-QTL and external-omics analyses were treated as supportive or limiting evidence. Results: Higher genetically predicted ALM was associated with lower ALT and lower T2D risk, whereas higher genetically predicted ALT was associated with greater T2D risk. T2D→ALT was method-dependent. In MVMR, the ALT conditional effect remained positive, whereas the ALM direct effect was model-dependent. Path decomposition was compatible with an ALT-related statistical pathway, but product- and difference-based estimates disagreed, and residual heterogeneity remained. ALM-T2DGGI supported an rs28929474-related shared component, although component-cohort overlap was possible. FinnGen supported other ALT-related signals but did not independently corroborate rs28929474. Tissue eQTL and external omics did not provide consistent mechanistic support. Conclusions: The data support directionally connected MR-based associations and dataset-dependent shared candidate signals. These findings do not establish biological mediation, a unique causal variant, gene-level causal assignment, or a molecular mechanism.

Background: Community-acquired intra-abdominal infections (CA-IAIs) exhibit significant clinical heterogeneity. However, most studies focusing on CA-IAIs do not stratify comparisons by infection site. Methods: This post hoc analysis of the prospective multicenter PERICOM cohort (13 French university hospitals, April 2018 to February 2019) included adult patients with CA-IAIs requiring surgical management. We compared clinical characteristics, microbiology, and outcomes between appendicular and non-appendicular sites. Secondary analyses assessed the impact of Enterococcus spp., Pseudomonas aeruginosa, or fungal documentation, and the theoretical coverage of empirical antibiotic regimens. Results: Of the 205 patients, 86 (42%) had appendicular and 119 (58%) had non-appendicular CA-IAIs. Appendicular CA-IAIs involved younger patients with fewer comorbidities and were followed by fewer major postoperative complications (Clavien-Dindo score ≥ 3: 10% versus 43%, p < 0.001) and no deaths (0% versus 12%, p < 0.001). Among 118 culture-positive patients, appendicular CA-IAIs showed higher rates of non-fermenting Gram-negative bacilli (25% versus 10%, p = 0.046) and anaerobes (53% versus 28%, p = 0.008) and were more often polymicrobial (76% versus 55%, p = 0.020). Conversely, Staphylococcus spp. (0% versus 9%, p = 0.036) and fungal co-infection (0% versus 12%, p = 0.010) were confined to non-appendicular CA-IAIs. Furthermore, Enterococcus spp. documentation (24/118, 20%) identified patients with greater admission severity and higher 28-day mortality (33% versus 2%, p < 0.001). Amoxicillin-clavulanic acid plus gentamicin covered the isolates of 92% of patients versus 61% for third-generation cephalosporin plus metronidazole (p < 0.001), a difference identical in both appendicular and non-appendicular sites. Conclusions: Appendicular and non-appendicular CA-IAIs appear to be distinct entities, supporting stratified management. Future guidelines should consider site-specific strategies, therapeutic individualization, and the integration of CA-IAI ecology.