Systemic lupus erythematosus (SLE) exhibits marked clinical and biological heterogeneity that is poorly captured by group-based analyses. Using the MRL/Lpr model, we describe an individual mouse displaying a severe phenotype, and provide a characterization combining clinical assessment, inflammatory profiling, neuroaxonal injury, and targeted metabolomics. Despite severe disease, this animal did not display a globally exaggerated cytokine profile relative to other MRL/Lpr mice, although TNF alpha and IL-1 beta ranked among the highest in the cohort. In contrast, plasma neurofilament light chain (NfL) was markedly elevated, and metabolomic profiling revealed pronounced disruptions in urea-cycle intermediates, sulfur amino-acid metabolism and muscle-derived metabolites, together with a broad depletion of circulating amino acids. These observations raise the possibility that, at advanced disease stages, circulating cytokine levels may plateau and lose discriminative capacity, whereas metabolic readouts may retain greater capacity to track disease severity.
Genetic diagnosis is increasingly crucial in medically assisted reproduction (MAR), enabling identification of infertility causes and guiding personalized treatments. This study investigates the genetic basis of empty follicle syndrome (EFS) in two independent consanguineous Algerian families with primary infertility. Exome sequencing and in silico analysis of a comprehensive infertility gene panel were performed on two index cases. Variants were prioritized based on gene-disease relationships. The identified ZP1 variant was further analyzed by 3D protein modeling. A literature review was conducted in order to compare genotype–phenotype correlations for ZP1, ZP2, ZP3, and ZP4 variants. Both patients and two affected siblings harbored a homozygous ZP1 c.1097G > A p.(Arg366Gln) variant inherited from both heterozygous parents. This previously described variant appears to be recurrent in North African populations. Structural modeling supported its pathogenic effect, as it likely disrupts zona pellucida structure, essential for oocyte protection and fertilization. Literature review showed that phenotypes varied among reported ZP1 mutations, ranging from complete EFS to cases with successful pregnancies. Comparative analysis of ZP2, ZP3, and ZP4 variants highlighted their critical but distinct roles in oocyte biology. The recurrent ZP1 c.1097G > A p.(Arg366Gln) variant contributes to EFS in consanguineous North African families. Genetic diagnosis using targeted gene panels is valuable for personalized infertility care and counseling. Further research into genotype–phenotype relationships and therapeutic approaches is needed to improve management of ZP-related infertility.
Background:Renal denervation (RDN) has emerged as a promising device-based therapy for uncontrolled hypertension. Recent data from major cardiovascular conferences (EuroPCR, ESH, TCT 2025) provide unprecedented 3-year follow-up evidence on efficacy, safety, and clinical outcomes. Methods:We synthesize key findings from the SPYRAL HTN-ON MED 3-year final report, the Global Symplicity Registry DEFINE (GSR-DEFINE) real-world data, SPYRAL AFFIRM post-approval study, and pooled analyses on acute hypertensive events. Data sources are distiguisehed by level of evidence: randomized sham-controlled trials versus observational registry data. Results:At 3 years, SPYRAL HTN-ON MED demonstrated sustained office systolic blood pressure (SBP) reductions of -18.5 mmHg (RDN) versus -11.7 mmHg (sham), with treatment difference of -6.8 mmHg (p = 0.0002). The GSR-DEFINE registry (n = 3109) showed -20.5 mmHg office SBP reduction at 3 years with progressively increasing effect over time. Pooled analysis revealed a 43% reduction in acute hypertensive events with RDN. No renal artery stenosis or need for reintervention was observed through 3 years. Conclusion:These data support RDN as a potentially durable and safe adjunctive therapy for uncontrolled hypertension in appropriately selected patients. Benefits appear to extend to high-risk populations including patients with diabetes, chronic kidney disease, and prior stroke, though long-term cardiovascular outcome data remain awaited.
The optimal intake of artificial nutrition in critically ill patients remains unclear. While calorie and protein intakes affect glomerular function in patients with chronic kidney disease, their relation to renal function at the acute phase of intensive care is insufficiently documented. We aimed to study associations of a low-calorie and low-protein diet with renal outcomes in critically ill patients. This post hoc analysis of the NUTRIREA-3 randomized-controlled trial included 3036 mechanically ventilated patients with shock. Calorie and protein intakes during the first 7 days were either low (6 kcal/kg and 0.2–0.4 g protein/kg/d) or standard (25 kcal/kg and 1.0–1.3 g protein/kg/d). The primary outcome was the incidence of acute kidney disease (AKD) during the ICU stay (up to ICU discharge or day 90 after inclusion, whichever occurred first). AKD during the ICU stay occurred in 669 (44.6
Functional chest imaging using electrical impedance tomography (EIT) has experienced an impressive technological development since its invention in the early eighties of the last century. The number of experimental and clinical studies using this technology is continuously rising, and the increasing availability of devices approved for clinical use accelerates and diversifies its applications in patients. EIT is predominantly used in intensive care units but its utilisation in operating theatres, delivery rooms, pulmonary function laboratories and even remote outpatient settings is growing. Chest EIT is mainly applied to determine the regional distribution of pulmonary ventilation, aeration changes, and respiratory system mechanics both during mechanical ventilation and spontaneous breathing, but an increase in the use of chest EIT for imaging lung perfusion and cardiac action has recently been noted. The ongoing innovation of both EIT hardware and software, the new application fields, and the rising number of users of this technology require consensus on EIT terminology and definitions. This secures a common framework for conducting EIT studies, patient examinations and guarantees unified analysis of EIT data, documentation, reporting and comparability of findings. Our article provides a comprehensive consensus document on EIT terminology and definitions generated by EIT experts of the international TRanslational EIT development stuDy group in cooperation with the producers of EIT technology. It not only updates and extends the first consensus EIT terminology published in 2017, but also offers a new taxonomy of EIT measures, systematically based on the quantification of ventilation-related, heartbeat-related, and contrast-enhanced EIT signals. Thanks to its clear structure with tabulated recommended EIT terms, abbreviations, comprehensible explanations, notes, extensive literature sources and parameter calculations, EIT researchers, clinical users and manufacturers may use this document as a reference source of information relevant for chest EIT.
