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Spin density-weighted (SDW) and inversion recovery (IR) 23Na MRI provide different sodium contrasts with complementary information. Therefore, the aim was to develop a time-efficient sequence scheme capable of providing both contrasts by acquiring SDW and IR 23Na MRI data within a single sequence without additional measurement time. In the developed pulse sequence, the conventional 180° inversion pulse was divided into two successive 90° pulses, with an additional readout inserted between them. The sequence was initially evaluated in simulations and phantom measurements. Afterwards, it was applied in calf muscle measurements of six healthy volunteers to assess its practical feasibility and signal characteristics. All 23Na measurements were acquired at 7 T and compared to standard SDW and IR sequences. The interleaved SDW/IR sequence yielded image quality and contrast comparable to standard SDW and IR sequences. Phantom experiments showed slightly higher remaining T1-weighting in the interleaved sequence compared with standard SDW, resulting in only minor changes in image contrast. Fluid suppression was effective across all IR approaches, though efficiency decreased modestly with longer effective inversion pulse lengths. Spin dynamic simulations for IR 23Na MRI indicated slightly increased sensitivity to fluid suppression artifacts arising from B0 inhomogeneities in the interleaved sequence. In vivo calf muscle measurements did not reveal significant differences in the mean muscle signal between the interleaved SDW/IR sequence and the corresponding standard sequences. The proposed interleaved sequence enables simultaneous acquisition of 23Na SDW and IR contrasts, thereby reducing overall scan time and eliminating the need for co-registration.

Cancer survivors experience challenges in establishing sustained employability, i.e., return to work and work retention. We evaluated the effectiveness of a stages-of-change-based work participation program (STEPS) to support sustained employability in cancer survivors. A two-armed randomized controlled trial was conducted among employees diagnosed with cancer 3-18 months earlier. Participants completed questionnaires pre-randomization, and at 6- and 12-month of follow-up (T1 and T2). Mixed-effects modeling compared STEPS with usual care on working hours (sustained employability) and secondary outcomes. Of 239 included participants, 123 were randomly assigned to STEPS and 116 to usual care. There were no meaningful differences in weekly working hours between the STEPS and control groups during follow-up. However, strict STEPS protocol adherence was related to working fewer hours per week across T1 and T2 (- 3.6, 95%CI [- 6.90, - 0.36]) and at T1 specifically (- 3.9, 95%CI [- 7.47, - 0.28]). Participants in STEPS who had returned to work to some extent at baseline worked fewer hours at T1 (- 3.7, 95%CI [- 7.16, -0.22]). Finally, participants in STEPS had 0.7-point higher best-ever work ability at T2 (95%CI [0.04, 1.31]). All other outcomes did not differ meaningfully between groups. In its current form, STEPS does not improve sustained employability in cancer survivors. While STEPS may improve self-perceived work ability, this is unlikely to improve objective work-related outcomes. Work participation support should extend beyond initial return to work and engage employees and employers to address workplace barriers and facilitators.

Cardiovascular (CV) disease is the leading cause of maternal mortality worldwide and has been partially linked to the cardiometabolic remodeling required to support fetal growth. In healthy pregnancies, these adaptations reverse postpartum without long-term consequences; however, impaired reverse remodeling (RR) increases future CV risk. Pregnant women living with HIV face additional risk, though it remains unclear whether this is driven by chronic low-level viremia or continuous antiretroviral therapy (ART). ART used during pregnancy often includes nucleoside reverse transcriptase inhibitors (NRTIs), which can affect mitochondria - organelles essential for maintaining cardiac function. Here, we tested the hypothesis that NRTI-containing ART negatively impacts the maternal heart. Using a rat model, we show that ART impairs pregnancy-associated cardiac RR. Mechanistically, ART induced mitochondrial alterations in both the heart and the liver, leading to dyslipidemia that collectively compromised cardiac function. These findings emphasize the importance of maternal cardiovascular health research and the need for further studies on the long-term effects of ART.

Leukodystrophies are inherited disorders that primarily affect the central nervous system white matter and often present with nonspecific symptoms, making early diagnosis difficult. Magnetic resonance imaging (MRI) is the key initial imaging test because it reveals characteristic myelin patterns that can guide biochemical and genetic workups. To review clinically useful MRI and MR spectroscopy (MRS) patterns in major leukodystrophies and emphasize their diagnostic relevance using a practical, pattern-recognition approach. Narrative review of the literature integrating conventional MRI, including T1/T2 fluid-attenuated inversion recovery (FLAIR), and diffusion-weighted imaging (DWI), as well as advanced techniques (MRS), with a pictorial, case-based approach. The pivotal imaging distinction is between hypomyelination-diffuse, persistent T2/FLAIR hyperintensity with relative temporal stability and absent enhancement-and demyelination, characterized by confluent, progressive lesions with disorder-specific topographic predilection. Recognizable signatures include U-fiber sparing and a tigroid pattern in metachromatic leukodystrophy (MLD); parieto-occipital predominance with trizonal enhancement and restricted diffusion in X-linked adrenoleukodystrophy (X-ALD); frontal predominance and the "tadpole sign" in Alexander's disease; optic pathway and thalamic involvement in Krabbe's disease; markedly elevated N-acetylaspartate (NAA) on MRS in Canavan's disease; and tract-selective leukoencephalopathy brainstem/spinal cord involvement with a lactate peak (LBSL). These imaging clues refine differential diagnosis, guide targeted genetic testing, and support longitudinal monitoring. The use of MRI-especially when complemented by DWI and MRS-remains central for early recognition and classification of leukodystrophies. A structured, pattern-based approach integrating clinical context with imaging topography can reduce diagnostic delay and support timely management.

Understanding how molecular structure governs photoinduced spin evolution in organic diradicals is essential for the rational design of spin-responsive molecular materials. Here, we investigate temperature-dependent excited-state relaxation dynamics of syn- and anti-indenoindenodibenzothiophene (IIDBT) diradicaloids using variable-temperature steady-state and transient absorption spectroscopies. Vibronic progressions in the high-energy, nonfrontier-orbital π-π* transition absorptions and low-energy frontier-orbital transition absorptions prompt strong couplings between electronic excitation, on one hand, and molecular vibrations, on the other hand. With the help of ultrafast spectroscopy, we identified multistep excited-state relaxation pathways including a "hot" singlet excited state, an intermediate state of mixed electronic and spin character, and a long-lived triplet excited state, following either low- or high-energy excitations. Notably, intersystem crossing (ISC) in IIDBT diradicaloids is enabled by vibrationally activated spin-orbit coupling, in which spin-vibronic coupling enhances singlet-triplet mixing along nuclear coordinates, leading to a fast and efficient interconversion between singlet and triplet excited states. Molecular control over both the vibronic coupling strength and spin evolution is also emphasized. This work establishes a clear experimental link between molecular vibration and spin-dependent excited-state dynamics in organic diradicals, providing a general framework for understanding and controlling ISC in open-shell organic systems.

Stereo-electroencephalography (SEEG) is increasingly utilized in surgical epilepsy evaluations, however, more robust preoperative data can aid in localizing and focusing SEEG electrode placement. Automated MRI volumetric analysis in patients with drug-resistant epilepsy may help predict aspects of the seizure network, as confirmed with invasive SEEG analysis. Pre-operative MRIs of patients undergoing SEEG investigation were analyzed using an automated volumetric platform and compared to age- and sex-matched controls. The patient's seizure network was parsed into subcomponents based on the SEEG investigation and compared to volumetric data. Nineteen patients were analyzed. On logistic regression, each one standard deviation increase in regional volume increased the odds that a region was part of the irritative zone (OR 1.36, 95% CI = [1.08, 1.71], p = 0.009), though this estimate should be considered exploratory given the non-independence of regions within patients. In patients with temporal lobe epilepsy (15/19), increased volume was associated with the irritative zone (OR 1.49, CI = [1.16,1.93], p = 0.002) and the seizure network overall (OR 1.31, CI = [1.04, 1.65], p = 0.023), while decreased volume was suggestive of non-involvement with the network (OR 0.76, CI = [0.60, 0.96], p = 0.023). Regions with an increased cortical volume as determined by rapid, automated volumetric analysis were more likely to be part of the seizure network irritative zone. This may represent a novel avenue for a low-cost, non-invasive analysis of patients' seizure networks. Further work is needed to better elucidate the relationship between cortical volumes and seizure networks and determine the potential of using automated volumetric analysis as a non-invasive tool in the preoperative work-up.

Fumarate hydratase (FH)-deficient renal cell carcinoma (RCC) is a rare, molecularly defined subgroup of non-clear cell RCC (nccRCC) lacking an approved standard treatment. We report the exploratory analysis of this entity within the SUNNIFORECAST trial. SUNNIFORECAST evaluated ipilimumab/nivolumab versus standard of care (SOC) in previously untreated, advanced nccRCC. The primary endpoint was the 12-months overall survival (OS) rate. Secondary endpoints included median OS, progression free survival (PFS) and overall response rate (ORR). PD-L1 expression was assessed exploratorily. Of 309 randomized patients, 30 had centrally confirmed FH-deficient RCC (ipilimumab/nivolumab, n=14; SOC, n= 16). The 12-months OS rate was 85.7% (95% confidence interval [CI] 53.9-96.2%) versus 73.3% (95% CI 43.6-89.1%), median OS was 35.7 months (95% CI 16.8 months-NE) versus 24.7 months (95% CI 10.6-37.7 months, hazard ratio [HR] 0.46 [0.17-1.20]), and ORR 42.9% versus 33.3%, favoring ipilimumab/nivolumab. Twenty-four patients were evaluable for PD-L1 expression; 21 had a combined positive score (CPS) ≥1. In this subgroup, the 12-months OS rate was 80.0% (95% CI 40.9-94.6%) versus 72.7% (95% CI 37.1-90.3%), median OS 38.3 months (95% CI 8.8 months-NE) versus 24.7 months (95% CI 8.8 months-NE, HR 0.43 [0.14-1.34]) and ORR 40.0% versus 36.4% for ipilimumab/nivolumab versus SOC, respectively. Exploratory analyses suggest trends toward improved 12-months OS-rate, median OS and ORR with ipilimumab/nivolumab versus SOC in FH-deficient RCC. The majority of tumors demonstrated PD-L1-expression (e.g. CPS ≥ 1), warranting further investigation in prospective studies.

The purpose of the study is to compare the efficacy and safety of available interventions for infantile hemangioma against oral propranolol and to evaluate the certainty of the comparative evidence. We conducted a Bayesian network meta-analysis in accordance with PRISMA-NMA guidelines and systematically searched PubMed, Embase, the Cochrane Library, and CNKI from January 2008 to June 2026. A random-effects consistency model was fitted using the BUGSnet package. Evidence certainty was assessed using the CINeMA framework, and risk of bias was evaluated using the revised Cochrane RoB 2 tool. Thirty randomized controlled trials (RCTs) including 2,639 patients across nine treatment nodes were included in the efficacy analysis, and 12 RCTs involving 1,143 patients across eight nodes were included in the safety analysis. Using oral propranolol as the reference treatment, no active intervention demonstrated statistically significant superiority in efficacy, whereas placebo was significantly inferior. Corticosteroids were the only intervention associated with substantially higher adverse event rates, whereas atenolol showed a trend toward fewer adverse events. By anchoring all comparisons to oral propranolol and integrating CINeMA certainty assessments with inconsistency testing, these findings are consistent with the continued role of oral propranolol as the reference systemic treatment for infantile hemangioma. For patients intolerant to propranolol, atenolol may represent a reasonable alternative.  By anchoring all comparisons to oral propranolol and integrating CINeMA certainty assessments with inconsistency testing, these findings are consistent with the continued role of oral propranolol as the reference systemic treatment for infantile hemangioma. For patients intolerant to propranolol, atenolol may represent a reasonable alternative. • Oral propranolol is the established first-line systemic therapy for infantile hemangioma. • Previous network meta-analyses have reported treatment rankings, but the clinical meaning of these rankings relative to oral propranolol remains uncertain. • Despite favorable point estimates for combination therapy and nadolol, this benchmark-anchored analysis found no included active intervention statistically superior to oral propranolol. • Certainty assessment showed that treatment rankings were limited by heterogeneity, inconsistency, risk of bias, and imprecision; atenolol had the largest body of direct comparative evidence among the alternatives.

Aminoacyl-tRNA synthetases (ARSs) are a family of enzymes that attach amino acids to tRNAs. To date, all 37 human ARS genes have been implicated in genetic diseases, affecting over a thousand patients worldwide. At the 2025 Federation of European Biochemical Societies (FEBS) Special Meeting 'Expanding Frontiers in Aminoacyl-tRNA Synthetase Research', patients, families, and advocacy groups communicated the need for a unified approach for reporting on ARS gene names and associated conditions in the scientific literature. This request stemmed from the current use of multiple nomenclature systems and the desire of these individuals to rapidly identify published data on specific ARS genes. Here, we summarize ARS gene nomenclature and request that the scientific community adhere to a single nomenclature system.

Coronary artery disease (CAD) remains the leading cause of death and current screening methods are limited. Color fundus photography (CFP) has been explored in literature mostly on the basis of associations and exploratory deep learning approaches with only indirect end points. In this explorative study, we aimed to assess the predictive abilities and limitations of explainable CFP-based features using machine learning and same-visit coronary angiography (CA) outcomes as end points for the first time. Patients undergoing CA were imaged with CFP (Zeiss Clarus 500, Zeiss, Oberkochen, Germany) during the same visit. Coronary plaque burden was assessed using the Gensini Score. Retinal features were extracted using Automorph. Machine learning models were trained and evaluated using fivefold cross-validation. Shapley additive explanations (SHAP) values quantified feature importance and interactions. Of 977 screened patients, 632 (1293 eyes) were assessed. CFP features alone reached moderate predictive performance (area under the receiver operating characteristic (AUROC) 0.692). Adding dimensionally reduced CFP features to clinical baselines consistently improved performance, with the best configuration yielding an AUROC 0.775, average precision (AP) 0.752, and Brier score 0.203. Net reclassification improvement (NRI)/integrated discrimination improvement (IDI) analyses supported improved reclassification for age + sex and basic clinical baseline models, but not for extended clinical baseline models. SHAP analysis revealed vessel width, density, and tortuosity as important vascular retinal indicators of CAD burden. Interaction analysis revealed nonlinear, age-, sex-, and diabetes-dependent effects. CFP features modestly improved the CAD classification beyond clinical baselines. Our findings illustrate the potential and the limitations of CFP features and indicate the need for complex modeling, methodological improvement, and multimodal approaches to achieve valuable classification efficacy.

The incompleteness of the fossil record and the absence of genetic information limit our ability to understand ancient developmental processes and reconstruct their evolution. Gene expression patterns, physiological pathways, or cellular differentiation processes are rarely preserved, leaving major gaps in our understanding of developmental evolution. Here, we combine comparative and mathematical analyses to uncover an ancestral patterning mechanism underlying the specification of liverwort oil body cells, a synapomorphy of the lineage involved in anti-herbivory defense. We demonstrate that oil body cell homologs in fossils of the oldest known liverwort (Metzgeriothallus sharonae) exhibit spatial organization characteristic of lateral inhibition, including regular spacing and an over-representation of idioblasts. We show that a mechanism involving local activation and lateral inhibition reproduces the diversity of patterns observed in the fossils. Finally, we find that the same mechanism can explain oil body cell patterns in the distantly related liverworts Treubia lacunosa, Apotreubia nana, and Marchantia polymorpha, suggesting a deeply conserved mode of cell specification. Our findings illuminate the origin and diversification of oil body cells, underscoring their evolutionary significance for liverwort development and survival.

Chimeric antigen receptor (CAR)-expressing cells bear a great potential for the treatment of autoimmune diseases. While numerous challenges persist, recent technological developments have demonstrated the potential for CAR cells to reset dysfunctional immune systems and transform care for patients with autoimmune disease.

Geriatric medicine is becoming increasingly more important in the context of demographic change. Older people frequently suffer from multimorbidity, functional impairments and complex psychosocial conditions that are often insufficiently addressed by a purely diagnosis-oriented medical approach. The primary aim of geriatrics is therefore not only the treatment of diseases but also with respect to individual goals, the preservation of independence, quality of life and social participation.This expert paper outlines the current state of geriatric care in Germany, its scientific evidence base and key challenges and future perspectives. Central elements of geriatric complexity medicine include comprehensive geriatric assessment, multiprofessional treatment concepts and cross-sectoral models of care. Numerous studies demonstrate that this approach improves functional outcomes, reduces the risk of long-term care dependency and reduces or shortens hospital stays.Despite established acute geriatric and rehabilitation structures, substantial deficits remain in nationwide access to care, financing, academic integration, research and professional training. Workforce shortages, insufficient outpatient services and the limited integration of geriatric principles into other medical specialties weaken the great opportunity that modern geriatric medicine offers for preventing the need for long-term care. At the same time, digitalization, telemedicine and innovative cross-sectoral care models offer new opportunities for patient-centered geriatric medicine.The authors advocate stronger structural and political support for geriatrics, the expansion of outpatient geriatric centers, financing systems that adequately reflect patient complexity and a stronger integration of geriatrics into research, teaching and medical education including a German Center for Geriatric Medicine with substantial involvement of geriatrics. In this way, geriatrics can make a major contribution to a sustainable, patient-centered and future-oriented healthcare system. Die geriatrische Medizin gewinnt angesichts des demografischen Wandels zunehmend an Bedeutung. Ältere Menschen leiden häufig an Multimorbidität, funktionellen Einschränkungen und komplexen psychosozialen Problemlagen, die durch eine rein diagnoseorientierte Medizin nicht ausreichend berücksichtigt werden. Ziel der Geriatrie ist daher nicht allein die Behandlung einzelner Erkrankungen, sondern, auf Basis individueller Ziele, der Erhalt von Selbstständigkeit, Lebensqualität und gesellschaftlicher Teilhabe.Das vorliegende Expertenpapier beschreibt den aktuellen Stand der geriatrischen Versorgung in Deutschland, ihre wissenschaftliche Evidenz sowie zentrale Herausforderungen und Zukunftsperspektiven. Im Mittelpunkt steht die geriatrische Komplexitätsmedizin mit dem geriatrischen Assessment, multiprofessionellen Behandlungskonzepten und sektorenübergreifenden Versorgungsmodellen. Zahlreiche Studien belegen, dass dadurch funktionelle Fähigkeiten verbessert, Pflegebedürftigkeit reduziert und Krankenhausaufenthalte verringert oder verkürzt werden.Trotz etablierter akutgeriatrischer und rehabilitativer Strukturen bestehen weiterhin erhebliche Defizite in der flächendeckenden Versorgung, der Finanzierung, der universitären Verankerung sowie in Forschung und Weiterbildung. Besonders der Fachkräftemangel, unzureichende ambulante und präventive Angebote und die mangelnde Integration geriatrischer Prinzipien in andere Fachgebiete schwächen die große Chance, die eine moderne Altersmedizin zur Vermeidung von Pflegebedürftigkeit bietet. Gleichzeitig eröffnen Digitalisierung, Telemedizin und innovative sektorenübergreifende Versorgungskonzepte neue Möglichkeiten.Die Autorinnen und Autoren fordern eine strukturelle und politische Förderung der Geriatrie, den Ausbau ambulanter geriatrischer Zentren, eine an Komplexität und Funktionalität orientierte Finanzierung sowie eine intensivere wissenschaftliche und akademische Verankerung, inklusive eines Deutschen Zentrums für Altersmedizin mit starker Beteiligung der Geriatrie. Die Geriatrie kann damit einen entscheidenden Beitrag zu einem nachhaltigen, patientenzentrierten und zukunftsfähigen Gesundheitssystem leisten.

Sagittal plane tibial geometry is a critical and modifiable determinant of outcomes in posterior cruciate ligament (PCL) insufficiency and genu recurvatum. The posterior tibial slope normally ranges from 7° to 10°, and pathological mechanics arise when it falls below 5° or becomes reversed. In PCL insufficiency, a flattened slope substantially increases graft failure risk, with long-term data demonstrating markedly reduced 10-year survival for patients with severely flattened medial and lateral slopes. Biomechanically, tibial slope exerts a linear, independently significant effect on PCL graft force in loaded states, and flattened slopes further worsen multiplanar instability following combined ligament reconstruction. In genu recurvatum, a flat or negative slope amplifies a chronic hyperextension moment that overstresses the posterior capsule and posterolateral ligamentous complexes, producing pain, weakness, instability and functional impairment. Both conditions share a common biomechanical root and benefit from surgical correction through anterior opening-wedge high tibial osteotomy (AOW-HTO), which restores physiologic slope by shifting the tibial resting position anteriorly and reducing posterior sag. Surgical planning relies on calibrated radiographs, with each millimetre of opening corresponding to approximately 2° of correction; three-dimensional computed tomography planning with patient-specific cutting guides adds accuracy for complex or biplanar deformities. Three operative approaches are described, supratuberosity, trans-tuberosity and infratuberosity, each with distinct implications for patellar height, healing potential and concurrent ligamentous procedures. Published data report mean slope increases of 9°-24° with 70%-90% good-to-excellent functional outcomes, and modern tuberosity-sparing techniques have expanded indications while preserving patellofemoral mechanics. Principal complications include hinge fractures, patella baja, implant irritation and iatrogenic extension loss, mitigated by meticulous technique and mandatory intraoperative extension testing. Four illustrative cases, spanning recurrent PCL insufficiency, growth-arrest-related recurvatum treated with acute and gradual correction and a biplanar osteotomy combined with revision PCL reconstruction in a professional athlete, demonstrate the breadth of application. The evidence base remains predominantly Level III-IV and prospective comparative studies are needed; nevertheless, AOW-HTO is an effective, joint-preserving procedure and a valuable adjunct to ligamentous reconstruction in patients with pathological sagittal malalignment. LEVEL OF EVIDENCE: Level V.

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The Y chromosome has been omitted from almost all phylogenomic analyses to date due to its complex structure, which makes accurate assembly and alignment across species challenging. Yet the Y chromosome is, in theory, an optimal phylogenetic marker. Y-chromosomal genes have a smaller effective population size than autosomal genes, reducing the likelihood of incomplete lineage sorting. Likewise, heterogametic hybrid offspring of different species are generally sterile, creating a barrier to Y-chromosomal gene flow. To overcome difficulties in using the Y chromosome, we developed a novel approach to identify orthologous Y-linked sequences in placental mammals, enabling us to generate a 63-species Y-chromosome alignment. We aligned ∼80 kilobases of predominantly non-coding sequence from conserved genes that are broadly expressed regulators of protein synthesis and spermatogenesis - the X-degenerate genes. Our phylogenetic reconstructions demonstrate that noncoding X-degenerate gene sequences recapitulate the same phylogeny derived from genome-wide noncoding, neutrally evolved sequences across the biparentally inherited autosomes and the X chromosome. We find strong support for the superordinal clades Euarchonta, Scrotifera, Fereuungulata, and Zooamata - groupings that have been historically considered controversial. Our results demonstrate that not only can the Y chromosome be aligned across species divergences spanning more than 100 million years, but it also performs robustly in a comparative phylogenetic context. We also present evidence that interchromosomal gene conversion between the non-recombining ZFX and ZFY genes has independently occurred in multiple lineages. ZFY has a proposed function as a meiotic executioner, and interchromosomal gene conversion may serve as a compensatory mechanism to prevent genetic decay of this essential gene.

Achieving spatially resolved chemical functionalization on graphene lattices is essential for fabricating advanced two-dimensional (2D) architectures. However, current covalent patterning strategies struggle to simultaneously minimize energy input for lattice preservation and offer the chemical versatility required for fine-tuning the local doping state of the 2D lattice. Here, a modular diaryl-sulfonium platform is developed for the ultra-low-threshold covalent patterning of monolayer graphene, further enabling substituent-encoded pattern of local work-function. Driven by a highly efficient, graphene-mediated hot-electron single-electron transfer (SET) mechanism, this approach lowers activation barriers, enabling non-destructive patterning with laser powers as low as 0.10 mW and irradiation time of a few seconds-orders of magnitude lower than conventional photon-driven processes-thereby ensuring high pattern fidelity without thermal degradation. By incorporating a library of six chemically distinct σ-bound substituents (including phenyl, fluorophenyl, trifluoroethyl, vinyl, phenylthiophenyl, and bromoethyl) onto a unified sulfonium scaffold, precise control over local work-function can be achieved. Kelvin Probe Force Microscopy (KPFM) reveals a continuous, chemically tunable spectrum of surface potential shifts (ΔCPD from ∼30 to ∼300 mV). Combined with exceptional ambient stability and thermal erasability, this work offers a robust, energy-efficient paradigm for chemically encoding reconfigurable 2D electronic landscapes.

Transthyretin cardiac amyloidosis (ATTR-CM) is a progressive, underdiagnosed cause of heart failure (HF). Diagnostic delays may increase cardiac injury at treatment initiation, but the relationship between delay and outcomes remains poorly defined. The purpose of this study was to evaluate time from HF diagnosis to ATTR-CM diagnosis as a proxy for disease progression and its association with HF hospitalization (HFH) and mortality. This retrospective cohort study used Medicare fee-for-service and Veterans Health Administration (VHA) data. We identified patients diagnosed with ATTR-CM between 2016 and 2022 using a validated algorithm based on diagnoses and medications. Time-to-diagnosis was defined as days between each patient's first HF diagnosis and first amyloid diagnosis. Using multivariable Cox models, we evaluated its association with death or HFH. We identified 7,770 Medicare beneficiaries and 2,557 Veterans with HF and ATTR-CM. Median age at diagnosis was 81 years in both cohorts (Medicare IQR: 76-86; VHA IQR: 74-87); women comprised 1,775 (22.8%) of Medicare and 13 (0.5%) of VHA patients. Median time-to-diagnosis was 494 days (IQR: 63-1,340) for Medicare and 490 days (IQR: 69-1,286) for VHA. After adjustment for sociodemographics, each 1-year delay was associated with a 7% increased risk of the primary outcome (Medicare HR: 1.07; 95% CI: 1.06-1.08; VHA HR: 1.07; 95% CI: 1.05-1.09). Results were similar after adjusting for comorbidities. Across 2 real-world populations, diagnostic delay in ATTR-CM is a clinically meaningful marker of disease progression, with longer delays associated with increased HFH and mortality.

Knowledge about the epidemiology of Lyme borreliosis in Austria remains limited. We conducted a nationwide cross-sectional study among blood donors from all Austrian provinces to assess the exposure to Borrelia burgorferi sensu lato. A total of 1841 serum samples from blood donors aged between 18 and 69 years were tested for Borrelia-specific IgG and IgM. Associations with age, sex, province and the residential altitude were assessed for both the one-tier and two-tier methods. IgG seroprevalence was 14% for one-tier and 7% for the two-tier. A consistent increase in age was observed for both approaches. Using the 20-29-year age group as reference, the strongest association was observed in individuals aged 60-69 years. The IgG positivity was higher among males than females for both the one-tier and two-tier tests. Regional analysis revealed substantial variation in IgG seroprevalence, with the lowest prevalence recorded in Tyrol and the highest in Carinthia. These differences were not attributable to age distribution. An additional analysis revealed a correlation between the seroprevalence and the altitude of residence. IgM seroprevalence did not differ significantly between the one-tier and two-tier approaches (7% and 6%), and no age-, sex-, or region-related trends were identified. Our findings demonstrate demographic and regional differences in exposure to Borrelia burgdorferi. Higher altitude of residence is associated with reduced exposure to the spirochetes. The findings emphasize the importance of Lyme borreliosis surveillance and help identify the groups and areas most likely to profit from targeted prevention.