Argentine hemorrhagic fever (AHF) is a disease caused by the Junín virus (JUNV) that can be fatal in 15%-30% of untreated cases. Although JUNV is the only arenavirus for which efficient therapy and vaccination have been established, its administration is limited. In this study, hybridoma technology was used to generate 30 mouse monoclonal antibodies (mAbs) against the glycoprotein complex (GPC) of JUNV. Of these 30 mAbs, 26 showed strong cross-binding to GPCs from various arenaviruses. In addition, nine mAbs demonstrated potent neutralizing activity in vitro with a 50% inhibitory concentration of less than 1 µg/mL against a replication-competent chimeric vesicular stomatitis virus expressing JUNV GPC (rVSV-JUNV), as well as the live attenuated JUNV vaccine strain Candid#1. Furthermore, when tested in vivo using a challenge model of rVSV-JUNV in Stat2[-/-] mice, five select mAbs significantly reduced viral loads in the spleen when administered prophylactically. Humanized versions of JUNV-1A2, JUNV-1D5, and JUNV-5B12 mAbs, which showed protection in vivo in the Stat2[-/-] surrogate model, were produced. These antibodies were evaluated in a guinea pig challenge model of AHF and showed protective efficacy. Escape experiments with these humanized antibodies, as well as previously characterized antibodies, GB03 and JUN1, using rVSV-JUNV resulted in the acquisition of amino acid changes in the GP1 part of the GPC, which directly contacts host receptor transferrin receptor 1, indicating these sites could be key for future therapies. In summary, we generated mAbs that may be valuable for antibody-guided vaccine design and therapeutic development.

Background: Valvular heart disease frequently accompanies acute heart failure (AHF), yet most studies address single valve lesions, and the prognostic weight of concurrent multivalvular involvement is less well defined. We examined the prevalence of single- and multi-valve disease and its relationship with one-year mortality. Methods: We analyzed 530 consecutive patients enrolled in a prospective single-center AHF registry between February 2023 and June 2025 and followed for 12 months. Aortic, mitral and tricuspid disease was graded according to European Society of Cardiology/European Association of Cardiovascular Imaging (ESC/EACVI) criteria, a valve being considered involved when it carried at least moderate stenosis and/or regurgitation; multivalvular disease was defined as involvement of two or more valves. The primary endpoint was one-year all-cause mortality. Cox regression was adjusted for admission log N-terminal pro-B-type natriuretic peptide (NT-proBNP), frailty (Clinical Frailty Scale ≥ 5) and age. In-hospital acute kidney injury was examined descriptively but was not entered into the models, because it is ascertained after admission. Results: Overall, 71.3% of patients had at least one significantly diseased valve-mitral in 44.3%, tricuspid in 43.8% and aortic in 27.5%-and 34.9% had multivalvular involvement. One-year mortality rose stepwise with the number of valves involved: 19.7%, 24.9%, 36.3% and 54.0% for zero, one, two and three valves, respectively (log-rank p < 0.001), corresponding to a crude hazard ratio (HR) of 1.51 (95% confidence interval [CI] 1.28-1.78) per additional valve. Multivalvular versus single or no valve involvement carried a crude HR of 2.07 (1.51-2.84) and remained associated with mortality after adjustment (HR 1.48, 95% CI 1.06-2.07, p = 0.020), as did each additional valve (HR 1.22, 1.03-1.45, p = 0.023). Adjustment for clinically manifest right heart failure (HF) attenuated the association with mortality (HR 1.15, 95% CI 0.96-1.37), whereas the association with the triple composite remained significant (HR 1.19, 95% CI 1.03-1.36). Propensity-score adjustment excluding right HF retained the association with mortality (HR 1.43, 95% CI 1.02-2.00), whereas inclusion of right HF attenuated it (HR 1.33, 0.94-1.87). The association was not detectable in the 304 patients without clinically manifest right HF (HR 1.06, 0.80-1.41, p = 0.69). In a post-discharge sensitivity analysis, the adjusted associations were directionally similar but did not reach statistical significance. Conclusions: In hospitalized AHF, multivalvular involvement was common, followed a predominantly mitral-tricuspid pattern, and identified an older, frailer, more congested phenotype with substantial right-sided and chronic renal involvement. Valve burden showed a graded association with one-year mortality that persisted after adjustment for baseline prognostic characteristics, but was attenuated once right-sided involvement was taken into account, whether by direct adjustment or by propensity methods; the association was retained when right HF was omitted from the propensity model. Because right-sided variables lie downstream of significant tricuspid disease, this attenuation is what adjustment for an intermediate is expected to produce and does not establish absence of prognostic value. Cumulative valve burden is therefore best interpreted as a powerful phenotypic marker of a more advanced HF phenotype with prominent right-heart involvement, rather than as an independent causal determinant of mortality.

Background: The prognostic relevance of left ventricular ejection fraction (LVEF) categories in acute heart failure (AHF) remains debated. We compared the clinical phenotype of patients hospitalized for AHF with preserved (LVEF ≥ 50%) versus reduced (LVEF < 50%) ejection fraction (EF), and compared the prognostic influence of the two phenotypes on in-hospital and post-discharge mortality. Methods: We analyzed 530 consecutive patients enrolled in a prospective single-center AHF registry (February 2023-June 2025), followed through June 2026, grouped as preserved (LVEF ≥ 50%, n = 264) or reduced (LVEF < 50%, n = 266). Baseline characteristics, in-hospital course, and post-discharge events (death, renal replacement therapy [RRT], acute HF rehospitalization, and a triple composite) were compared. Given the distinct prognostic mechanisms operating during hospitalization and after discharge, the two periods were analyzed separately. In-hospital mortality was reported descriptively, whereas predictors of post-discharge mortality were evaluated using multivariable Cox regression with follow-up beginning at discharge. Results: Patients with preserved LVEF were older, predominantly women, and more often frail and in atrial fibrillation, whereas LVEF < 50% was associated with an ischemic etiology, right heart failure, and higher values of natriuretic peptides (all p < 0.05). In-hospital mortality was higher with LVEF < 50% (7.1% vs. 3.0%, p = 0.046) and was almost entirely cardiovascular (6.4% vs. 1.1%, p = 0.002). Among the 503 patients discharged alive, post-discharge mortality did not differ between phenotypes (27.7% vs. 22.7%, p = 0.23), nor did terminal RRT (2.7% vs. 3.2%) or the triple composite (49.6% vs. 42.1%, p = 0.11); emergency-department visits were more frequent with preserved LVEF (69.1% vs. 58.6%, p = 0.048). In the multivariable model of post-discharge mortality (n = 494, 124 deaths), frailty (HR 1.96, 95% CI 1.09-3.51) and log NT-proBNP (HR 1.86, 95% CI 1.45-2.38) were independent predictors, whereas worsening renal function was not. LVEF < 50% was associated with lower post-discharge mortality in the full model (HR 0.58, 95% CI 0.38-0.89), but this association was not robust across specifications, as follows: it disappeared when NT-proBNP was omitted (HR 0.88, 95% CI 0.60-1.27), and no alternative LVEF cut-point was associated with mortality. Conclusions: The two phenotypes are dissimilar in in-hospital mortality and similar in post-discharge mortality, with no consistent independent contribution to prognosis of this specific cut-off of LVEF of 50%.

The Junin virus (JUNV) is mainly perpetuated in nature by rodent reservoirs, especially Calomys musculinus, and is transmitted to humans through aerosolization of contaminated rodent excreta. Clinical presentation of Argentine haemorrhagic fever (AHF) is characterized by an incubation period of about 7-14 days and several clinical manifestations such as fever, malaise, hematological abnormalities, hemorrhagic symptoms and neurological complications. The current review summarizes the current knowledge on the taxonomy, structure, genome structure, transmission dynamics, pathogenesis, clinical syndrome, and diagnostic methods that are related to JUNV infection. Special emphasis is on the progress in the sphere of molecular diagnostics, immune plasma therapy, and antiviral studies. The introduction of the Candid #1 live attenuated vaccine is a significant step towards the prevention of the AHF and has greatly reduced the prevalence of the disease among the endemic populations. Recent scientific advances, such as reverse genetics systems, genomic surveillance, and new therapeutic strategies, have added to the knowledge of the biology of JUNV and its interplay with the host immune system. Nonetheless, there are still challenges because of further spreading of the viruses among the rodents (reservoirs), inability to develop specific antiviral therapies, and the potential of other related arenaviruses. Argentine hemorrhagic fever needs to be prevented, diagnosed and controlled by further research, enhanced surveillance systems and enhanced vaccination.

This 2026 consensus report from the European Association for the Study of Diabetes (EASD) and the American Diabetes Association (ADA) builds on the 2021 consensus report to provide guidance for managing type 1 diabetes in adults. Reflecting the rapid advances in the field, this update places particular emphasis on the integration of new technologies, while all sections have been revised to incorporate new evidence, advances in clinical practice and novel therapies, including interventions to delay the onset of stage 3 type 1 diabetes. It also broadens its scope to screening for long-term diabetes complications, and the management of obesity and cardiovascular risk factors. Psychosocial care and diabetes self-management education and support (DSMES) remain key elements. The report was developed using the Accurate Consensus Reporting Document (ACCORD) framework. The guidance aligns with the current ADA 'Standards of Care in Diabetes' (Standards of Care) and relevant EASD and ADA documents and aims to support clinicians globally in delivering high-quality, personalised care for adults with type 1 diabetes, with recommendations that can be adapted across diverse healthcare systems and resource settings.