Sepsis is a major cause of mortality worldwide, with modest improvements in the last decades. A significant challenge for the outcome improvement lies in the marked disease heterogeneity among patients. Stratifying patients into distinct endotypes is needed for more precise interventions. This study investigates the transcriptomic landscape of sepsis patients stratified by their inflammatory endotype. We obtained peripheral blood mononuclear cells from 125 sepsis patients (as per Sepsis-2 criteria) and 299 volunteers as part of the Functional Genomics in Severe Infections project (FUSE). RNA sequencing was conducted to identify differentially expressed genes and enriched pathways. We compared the transcriptomic profiles of previously defined "high-" and "low-inflammatory" endotypes, obtained through targeted inflammatory proteomics. Sepsis was linked to widespread transcriptional changes in innate immunity genes, notably those linked to phagocytosis and antimicrobial peptides, alongside paradoxical reduced NK cell-mediated immunity. Adaptive immunity genes, particularly those involved in T cell differentiation, were downregulated. Importantly, infection etiology and infection site had no discernible impact on gene expression profiles. In the "high-inflammatory" endotype, interferon-associated chemokines CXCL9 and CXCL10 were markedly upregulated at the transcription level in peripheral blood mononuclear cells, with concordant elevations in their circulating serum concentrations, as assessed by targeted proteomics and ELISA. Immune dysregulation in sepsis is more driven by disease severity than infection site. The robust activation of the interferon-gamma-CXCL9-CXCL10 axis observed in the "high-inflammatory" endotype may present a promising target for personalized immunotherapies.
Background and Objectives: Sepsis is one of the major causes of death in modern society. This study is part of the FUSE (Functional Genomics in Severe Sepsis) project under the Human Functional Genomics Romania initiative. Our aim was to assess the epidemiology of sepsis in a tertiary academic hospital in southwestern Romania. Materials and methods: The study enrolled 184 patients with severe infections between May 2017 and November 2019, following the Sepsis-2 guidelines (SIRS criteria). Results: The present cohort of community-acquired severe infections shows respiratory and urinary tract as main sites of severe infection. The demographic and clinical characteristics of this Romanian study group are in line with those of other severe infection European cohorts. However, the predominance of confirmed Clostridium difficile cases represents a strong deviation, raising significant concerns for the communities to which the patients belong. Conclusions: Sepsis, with its complex pathophysiology and clinical presentation, remains one of the most daunting global health issues. In our cohort, the high number of Clostridium difficile cases prompts high vigilance and immediate intervention.
Background/Objectives: Lung cancer remains the leading cause of cancer-related mortality worldwide, with a high proportion of cases diagnosed at advanced stages. Accurate mediastinal staging is essential to guide optimal therapeutic decisions. This study aimed to evaluate the diagnostic performance of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) and to develop a composite clinical–molecular score (EXPoSURE) for risk stratification. Methods: A retrospective study was performed that included 131 patients diagnosed with lung cancer between December 2023 and December 2024 at a regional oncology center in Oltenia, Romania. All patients underwent bronchoscopy and EBUS-TBNA using a standardized protocol. Clinical, pathological, and molecular data were collected to assess diagnostic yield, staging performance, and the association with molecular markers. The EXPoSURE score integrated PD-L1, p63, EGFR status, comorbidities, histological type, and TNM stage. Results: EBUS-TBNA provided a conclusive diagnosis in 91.6% of cases, with a low rebiopsy rate of 8.4% and no requirement for mediastinoscopy. Most patients (68%) were diagnosed at stage IV. PD-L1, p63, and EGFR expression showed no significant correlation with TNM stage, while the EXPoSURE score demonstrated promising stratification capability. Occupational exposure appeared to influence disease severity in some subgroups, although further validation is needed. Conclusions: EBUS-TBNA is a valuable, safe, and effective approach for minimally invasive diagnosis and mediastinal staging of lung cancer. The proposed EXPoSURE composite score may contribute to a multidimensional risk assessment, supporting more tailored management strategies and warranting prospective validation.
Background: Human Immunodeficiency Virus (HIV) is a virus that progressively impairs immune function by depleting CD4 + T-lymphocytes, ultimately leading to acquired immunodeficiency syndrome (AIDS). People living with HIV face a higher risk of developing various bone disorders, such as osteopenia, osteoporosis, and osteonecrosis. The aim of this study was to evaluate the bone mineral density (BMD) status, to determine the prevalence of osteopenia/osteoporosis and to identify the risk factors for low BMD in patients living with HIV undergoing antiretroviral treatment (ART), registered in Craiova Regional Center. Methods: A retrospective study was conducted between June 2024 and January 2025, including HIV-infected subjects aged over 18 years. Results: The study group included 106 patients. Dual-energy X-ray absorptiometry (DEXA) showed that 87 patients had low BMD, 51% having osteopenia and 31.1% having osteoporosis. We found a statistically significant correlation between low BMD and older age, higher levels HIV viremia, CD4 nadir < 200 cells/mm3, prolonged ART exposure and tenofovir disoproxil fumarate containing regimens. Conclusions: These findings support the inclusion of routine bone health monitoring in the standard care of patients with HIV, as well as the need for reevaluation.
Adults living with HIV (human immunodeficiency virus) infection (ALHIV) have high rates of cardiovascular events. New approaches are needed to detect subclinical cardiac dysfunction. We used conventional and speckle tracking echocardiography to investigate whether ALHIV display latent cardiac dysfunction. We analyzed 85 young subjects with HIV infection and free from cardiovascular risk factors (31 ± 4 years) and 80 matched healthy volunteers. We measured left ventricular (LV) layered global longitudinal strain, circumferential strain, peak longitudinal strain in the reservoir and contraction phases of the left atrium (LASr respectively LASct). In the HIV group, LV ejection fraction and s’ TDI (tissue doppler imaging) were slightly lower but still in the normal ranges. Layered longitudinal strain showed no significant difference, whereas circumferential global strain was significantly lower in the HIV group (−20.3 ± 3.9 vs. −22.3 ± 3.0, p < 0.001). LASr (34.3% ± 7.3% vs. 38.0% ± 6.9%, p < 0.001) was also lower in ALHIV and multivariate analysis showed that age (β = −0.737, p = 0.01) and infection duration (β = −0.221, p = 0.02) were independently associated with LASr. In the absence of cardiovascular risk factors, adults living with HIV display normal LV systolic function. Left atrial reservoir strain, is, however, decreased and suggests early diastolic dysfunction.
Measles remains an important cause of morbidity and mortality worldwide. Most HIV-infected adults are immune against measles, so titres of measles antibodies should be determined prior to vaccination. A measles vaccine can be administered to HIV-positive patients who do not have protective antibody levels and who have a CD4 lymphocyte count ≥ 200 cells/mm3. We describe the case of an HIV-infected patient, diagnosed with complicated measles at our Infectious Diseases Hospital in April 2024.