Acute organ dysfunction is a primary driver of ICU mortality. As clinical scores often act as lagging indicators, early recognition of subclinical endothelial stress may be essential for timely intervention. This exploratory study investigated the association of mid-regional pro-adrenomedullin (MR-proADM)—a stable surrogate of the hormone adrenomedullin—as a potential early indicator of early organ failure. This retrospective, single-center study analyzed a heterogeneous cohort of 26 critically ill patients. Plasma MR-proADM levels were assessed at admission (t0) and daily for 5 days. The primary outcome was the correlation between admission MR-proADM and the 24-h SOFA score. Secondary outcomes included comparisons between septic and non-septic patients and between survivors and non-survivors. Admission MR-proADM showed a moderate correlation with the 24-h SOFA score (rho = 0.488; p = 0.021), with the most prominent associations observed within the cardiovascular and renal SOFA domains. In the septic subgroup, MR-proADM levels were higher than in non-septic patients (10.90 [IQR 5.91–19.00] vs. 1.30 [IQR 0.74–2.53] nmol/L, p < 0.001); ROC analysis yielded an AUC of 0.88 (95
Elexacaftor-tezacaftor-ivacaftor (ETI) improves clinical outcomes in people with Cystic Fibrosis (pwCF), with possible anti-inflammatory properties. However, the molecular mechanisms underlying these effects remain unclear. This study investigates ETI’s anti-inflammatory and immunomodulatory activity, focusing on essential signaling pathways. Forty-nine pwCF were followed for 24 months. PwCF underwent clinical and pulmonary function assessment along with sweat test chloride measurement. Blood samples were analyzed for red and white blood cell counts and C-reactive protein (CRP). Plasma cytokines were quantified and phospho-kinase arrays and western blotting were used to assess protein phosphorylation in peripheral blood mononuclear cells (PBMC) from pwCF and healthy controls, pre- and post-ETI. Gene expression was evaluated in patient-derived PBMC and CF bronchial epithelial cells in vitro. ETI treatment significantly improved percent-predicted forced expiratory volume in 1 s (ppFEV1) and reduced intravenous antibiotic use. Inflammatory markers (including CRP) and circulating leukocytes decreased, especially lymphocytes and monocytes. Six of 27 pro-inflammatory cytokines were significantly downregulated. ETI strongly inhibited Signal Transducer and Activator of Transcription 5 (STAT5) phosphorylation in PBMC and CF epithelial cells, both in vivo and in vitro. This correlated with reduced interleukin IL-6, IL-8, and TNF-α mRNA levels. Pharmacological inhibition of JAK/STAT mimicked ETI effects on cytokine expression, supporting STAT5 as an important player involved in CF chronic inflammation. Long-term ETI treatment confirms clinical benefits and exerts measurable immunomodulatory effects, partially via inhibition of JAK/STAT signaling. These findings support its broader impact beyond CFTR correction. Further studies are warranted to explore long-term immunological outcomes, especially in younger patients initiating early therapy.
Bronchiectasis is a chronic respiratory disease characterised by permanent bronchial dilation, productive cough and recurrent exacerbations. Staphylococcus aureus (including methicillin-resistant strains (methicillin-resistant S. aureus (MRSA)) is increasingly recognised as a relevant pathogen in bronchiectasis, although its role remains less well defined than that of Pseudomonas aeruginosa or Haemophilus influenzae. This narrative review examines the epidemiological, pathophysiological, clinical and therapeutic implications of S. aureus infection in adults with bronchiectasis, drawing comparisons with other disease models. Epidemiological data reveal a lower prevalence of S. aureus in bronchiectasis compared to other pathogens, with significant regional variation. Its clinical impact is debated, with some studies associating chronic S. aureus infection with more severe disease, while others consider it a marker of severity rather than a direct driver of progression. Unlike P. aeruginosa, current guidelines do not recommend specific eradication or long-term suppressive strategies for S. aureus. British guidelines suggest MRSA eradication may be considered in cases of clinical deterioration, although no standardised protocol exists. Exacerbations are managed with a 14-day course of targeted antibiotics. Preventive strategies, including decolonisation and vaccine development, are under investigation or adapted from other clinical contexts. While no vaccine is currently available, monoclonal antibodies targeting S. aureus toxins have shown promise in early trials. Further research is needed to clarify the pathogen's role in disease progression and the efficacy of targeted therapies. This review also outlines clinical practice points and research priorities to support evidence-based management.
Articular patellar fractures (AO/OTA 34-C1/C2) are commonly treated with internal fixation. This non-randomized prospective observational study aimed to compare clinical and functional outcomes between two osteosynthesis techniques: contoured dorsal mini-fragment plate and tension band wiring. All patients who underwent surgical fixation for transverse articular patellar fractures between November 2023 and January 2025 were prospectively enrolled. Patients were divided into two groups: Group A, treated with a dorsal mini-fragment plate, and Group B, treated with tension band wiring. Demographic data, failure rate, hardware removal rate, and range of motion (ROM) at 1 year postoperatively were compared between groups. In addition, functional outcomes and quality of life were assessed at a minimum follow-up of 1 year using the Kujala Anterior Knee Pain Scale (AKPS) and the 12-Item Short Form Health Survey (SF-12). A total of 54 patients were included (Group A: n = 24; Group B: n = 30). Compared with Group B, Group A showed a lower failure rate (8.3
