• Indicator condition-guided HIV testing in patients with mononucleosis-like illness and community-acquired pneumonia in an Emergency Department setting: A prospective study from Poland (2015-2018).
    3 days ago
    Despite advances in HIV care, late diagnosis remains a major public health challenge in Europe, with nearly half of HIV diagnoses in the EU/EEA occurring at a late stage. In Poland, a substantial proportion of people living with HIV remain undiagnosed. Indicator condition-guided testing has been proposed as an effective strategy to reduce missed opportunities for earlier diagnosis.

    A prospective cohort study was conducted at the Emergency Department of the Hospital for Infectious Diseases in Warsaw, Poland, between May 2015 and March 2018, as part of the European OptTEST project. HIV DUO testing was offered to patients aged 18-65 years presenting with mononucleosis-like illness (MONO) or community-acquired pneumonia (CAP). We evaluated the prevalence of HIV infection and assessed linkage to HIV care among those testing positive. Confirmatory testing, CD4 cell counts at diagnosis, and linkage-to-care outcomes were collected.

    Among 885 patients with indicator conditions (MONO: 794; CAP: 91), 636 (71.9%) accepted HIV testing. Twenty-two patients (3.5%) were confirmed HIV-positive. HIV prevalence was 2.6% among patients with MONO and 11.1% among those with CAP. Most HIV-positive patients were male (90.9%), with 59% identifying as men who have sex with men or bisexual. The median age was 32.5 years. The median CD4 cell count at diagnosis was 341 cells/µL overall and was lower in patients presenting with CAP than MONO (61 vs. 366.5 cells/µL). All patients diagnosed with HIV were linked to care, and 95.5% initiated antiretroviral therapy, with a median time to treatment of 8 days.

    HIV seroprevalence among patients presenting with MONO or CAP was higher than the national average, particularly among those with CAP. These findings support routine indicator condition-guided HIV testing in Emergency Departments to improve early HIV diagnosis and timely linkage to care.
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  • Third-generation cephalosporin use is frequently non-guideline-concordant in severe community-acquired pneumonia: Findings from a French critical care cohort.
    3 days ago
    Severe community-acquired pneumonia (CAP) remains a major cause of morbidity and mortality, requiring prompt empirical antibiotic therapy. The choice between amoxicillin/clavulanic acid (AMC) and third-generation cephalosporin (3GC) as first-line beta-lactam therapy in the ICU is still debated. To assess AMC and 3GC susceptibility in severe CAP or community-acquired aspiration pneumonia (CAAP) caused by Streptococcus pneumoniae (SP), Haemophilus influenzae (HI) and/or Staphylococcus aureus (SA), and to evaluate the appropriateness of empirical antibiotic therapy.

    We conducted a single-center retrospective study including patients admitted to the ICU between 01/01/2018 and 30/11/2022 for severe CAP/CAAP with microbiological documentation of at least one of the targeted pathogens. Clinical, microbiological, therapeutic, and outcome data were collected. The primary endpoint was AMC and 3GC susceptibility rates (expressed as percentage and [95% confidence intervals]).

    Among 104 included patients (median age 64 [48-71] years; 67% male), 60 (57.7%) had CAAP. AMC susceptibility rates were 81.5% [61.9-93.7], 78.0% [62.4-89.4], and 100% [92.6-100.0], while 3GC susceptibility rates were 96.3% [81.0-99.9], 95.1% [83.5-99.4], and 100% [92.6-100.0], for SP, HI, and SA, respectively. AMC was the empirical treatment in 59% of cases, and this choice was microbiologically appropriate in 86.9% of these prescriptions. Conversely, 3GC were prescribed empirically in 20% of cases, but this broad-spectrum choice was unjustified in 80% of those situations. Antibiotic de-escalation was performed in 28% of cases.

    In this single-center retrospective cohort, AMC appears to be a relevant empirical option for severe CAP/CAAP in the ICU, while 3GCs seem frequently overused. These findings required prospective multicenter validation before practice change can be recommended.
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  • Empowering final-year student nurses through autonomous practice in district and community nursing placements.
    3 days ago
    Final-year student nurses were offered aspirant nurse roles to support busy clinical teams within district nursing services as part of the response to the COVID-19 pandemic. Student nurses in their final year of training had the opportunity to work as an aspirant nurse (paid band 4 position) for a 12-week period, as per the emergency education standards delivered by the Nursing and Midwifery Council in an effort to help out during the pandemic. This gave the students additional responsibilities to allow them to work autonomously but still under the supervision of the registered nurse. This role was separate to their student nurse role, becoming part of the clinical team where they were placed. Building on this concept, a collaboration between higher education institutions and the Essex Partnership University Trust resulted in the development of a structured pilot student autonomous visit programme, at the time referred to as non-direct supervision students. This initiative aimed at improving student learning and enhancing professional identity and confidence, while addressing challenges in recruitment and retention in community nursing roles. This article outlines the development and implementation of the pilot programme, evaluates its impact and discusses its implications for nurse education and workforce planning. Results indicate enhanced student preparedness and improved staff retention in district nursing, strengthening interprofessional collaboration between universities and NHS teams.
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  • Surgical management of refractory massive hemoptysis from pulmonary artery pseudoaneurysm due to Streptococcus constellatus: a rare case report and literature review.
    3 days ago
    Pulmonary artery pseudoaneurysm (PAP) is a rare but potentially fatal vascular lesion resulting from focal disruption of the pulmonary arterial wall. Although hemoptysis from the pulmonary arterial system is uncommon, PAP carries a high risk of rupture, with reported mortality rates up to 50%. PAP is most often caused by trauma or infection, with pyogenic bacteria and fungi as typical pathogens, while Streptococcus constellatus is an exceptionally rare cause. A 60-year-old woman with well-controlled type 2 diabetes presented with recurrent massive hemoptysis, fever, and right-sided pleuritic chest pain, without prior lung disease or trauma. She initially underwent emergency bronchial artery embolization (BAE) and antibiotic therapy for necrotizing pneumonia-associated hemoptysis, with no clinical improvement. Following the second BAE for recurrent massive hemoptysis, a PAP, possibly related to a bronchial-pulmonary arterial shunt, was suspected in the right lower lobe on angiography and subsequently confirmed on contrast-enhanced computed tomography. Despite optimal medical therapy, repeated BAE, and coil embolization of the PAP, hemoptysis persisted, and respiratory status deteriorated. The patient ultimately underwent video-assisted thoracoscopic right lower lobectomy, with intraoperative cultures of lung tissue and pleural fluid confirming S. constellatus, and achieved complete recovery without recurrent hemoptysis. PAP is a rare but potentially fatal cause of hemoptysis that requires a high index of suspicion. Although endovascular intervention is effective for initial hemorrhage control, persistent infection or refractory hemoptysis may necessitate surgical resection to achieve definitive management. This case highlights S. constellatus as an exceptionally rare infectious cause of PAP and underscores the importance of a multidisciplinary approach in complex, antibiotic-resistant cases.
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  • Perceptions of Spanish-language COVID-19 video messaging among the Hispanic community: A qualitative study in the United States of America.
    3 days ago
    With evidence linking credible and quality COVID-19 vaccine information to positive vaccination attitudes and intentions, it's vital to understand how communities facing health disparities access health information about COVID-19. This interview study of 49 Hispanic individuals in a large southern suburban county is a part of a larger three-year multi-method study. Through the lens of self-determination theory, this project investigates perceptions of four television-aired Spanish-language video messages on CseOVID-19 vaccination developed from findings of prior local focus groups and panel surveys supported by community partners. The present study's findings show human-centered, gain-frame messaging was positively received and highlight the need for targeted Spanish-language public health messaging in Spanish news media to improve quality information about COVID-19. Gentler suggestions for health protective behaviors may foster greater perceived resonance, credibility, and informational value of public health messages, with potential implications for psychological reactance and subsequent responses.
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  • Persistence of SARS-CoV-2 RNA Residues in Placenta Tissue Following Maternal COVID-19 Infection During Pregnancy.
    3 days ago
    Prolonged SARS-CoV-2 viral persistence was reported in extrapulmonary tissues in patients infected with COVID-19. SARS-CoV-2 can infect placental tissue. However, little is known about SARS-CoV-2 viral persistence in the placenta.

    This is a retrospective and IRB approved study. Placental tissue samples from 40 women infected with COVID-19 at various gestational age were analyzed. SARS-CoV-2 RNA expression was examined by in situ hybridization on placental disk and fetal membrane. S-protein and N-protein expression was determined by immunostaining. SARS-CoV-2 RNA sequencing was also performed in 12 out of the 29 cases in which SARS-CoV-2 RNA expression was detected positive by in situ hybridization.

    SARS-CoV-2 RNA expression was detected in placental disk, predominantly localized in syncytiotrophoblasts in 29 out of the 40 cases, but not in fetal membrane. Among the 29 positive cases, 4 infected in the first trimester, 7 in the second trimester, and 18 in the third trimester or at term. The longest interval from infection to delivery was 221 days. Among the 21 women who tested positive for COVID-19 at L/D admission, 18 (85.7%) detected SARS-CoV-2 RNA expression in placental tissue. Notably, 11 (57.9%) of 19 cases (negative test at L/D admission) detected viral RNA expression in placental villous tissue. Viral RNA expression was also detected in villous core vessel endothelium in two COVID (+) newborn placentas, with corresponding positive S-protein and N-protein expression in syncytiotrophoblasts. S-protein and N-protein expression was undetectable in 27 out of the 29 cases with positive detection of SARS-CoV-2 RNA expression. Partial RNA-dependent RNA polymerase (RdRp) region sequence was identified in all the 12 cases examined.

    These findings provide compelling evidence that SARS-CoV-2 genetic material can persist in placental tissue long after maternal infection, which may potentially contribute to a sustained inflammatory environment at the maternal-fetal interface during pregnancy. The phenomenon of partial RdRp sequence detected would provide a possible explanation for undetectable S- and N-protein expression in testing specimens.
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  • Impact of ABO Blood System on Immunogenicity and Vaccine Efficacy of COVID-19 Booster Vaccination-A Population-Based Study of 3066 Individuals.
    3 days ago
    ABO blood group has been associated with SARS-CoV-2 susceptibility. Little data exist regarding the impact of ABO and Rhesus (Rh[D]) type on breakthrough infections and antibody responses following SARS-CoV-2 booster vaccination.

    This multicenter, population-based cohort study includes individuals ≥ 18 years who received a booster vaccination against SARS-CoV-2. Antibody levels against SARS-CoV-2 receptor binding domain (RBD) and neutralizing antibodies against wild-type (WT) virus and Omicron variant were assessed at baseline, after 4 weeks and after 6 months. At 6 months follow-up, self-reported ABO and Rh(D) type, time to, and severity of breakthrough infections were collected.

    In total, 3066 participants (mean age 49 [35-59], 62% female) were included in multivariable regression models, showing no association of anti-RBD and neutralizing antibodies against wild-type and Omicron variant with ABO or Rh(D) 4 weeks after booster vaccination. Time-dependent Cox regression analysis showed significantly lower rates of breakthrough infections in patients with AB (hazard ratio [HR] 0.67 [0.50-0.90]; p = 0.008) compared to O, even after adjustment for relevant covariates and a trend for blood group B (HR 0.82 [0.66-1.01]; p = 0.06) compared to O; there were no associations between Rh(D) and breakthrough infection rates or between observed (asymptomatic to moderate) COVID-19 symptom severity and ABO or Rh(D) blood group.

    ABO or Rh(D) blood group was not associated with COVID-19 severity or antibody responses following SARS-CoV-2 vaccination. Breakthrough infections were least common in blood groups AB and B. Although our data do not support previously discussed protective effects of anti-A/B/Rh(D) agglutinins, differences in ABO group appear relevant for Omicron transmission.
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  • Endothelial Senescence-Associated Secretory Signaling Promotes Macrophage Extracellular Traps Formation and Contributes to the Exacerbation of Combined Lung Injury.
    3 days ago
    Radiation-induced lung injury (RILI) is a common complication of thoracic radiotherapy and can be critically exacerbated by pre-existing pulmonary inflammation, yet the synergistic mechanisms driving this pathology remain elusive. Using a murine model of combined lung injury induced by lipopolysaccharide (LPS) and thoracic irradiation (IR), we identified macrophage extracellular traps (METs), a type of web-like chromatin structure released by macrophages, rather than neutrophil extracellular traps (NETs), as a prominent pathogenic process. Mechanistically, the combination of LPS and irradiation induced an early endothelial senescence-associated phenotype and a CXC chemokine-enriched secretory profile. These signals engaged macrophage CXCR2, leading to p38/ERK pathway activation and reactive oxygen species (ROS) production that contributed to METs formation (METosis). Functionally, METs serve as potential dual-phase mediators, contributing to epithelial barrier disruption during acute injury and promoting epithelial-mesenchymal transition (EMT)-like epithelial remodeling, thereby potentially linking early inflammatory damage to subsequent fibrotic progression. Furthermore, we demonstrate that the bioactive compound Cordycepin exerts protective effects by suppressing p38/ERK pathway activation and attenuating METosis. Collectively, these findings support a potential endothelial senescence-associated secretory signaling-METosis axis, providing a novel mechanistic framework and candidate therapeutic strategies for managing high-risk radiation-induced lung injury.
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  • Auto-antibodies neutralizing type I interferons in ~10% of Moroccan patients with life-threatening COVID-19.
    3 days ago
    Autoantibodies neutralizing type I interferon (AAN-I-IFN) have been found in at least 10-15% of critical COVID-19 pneumonia cases in various studies across North and Latin America, Oceania, Europe, and Asia. We sought to analyze the prevalence of AAN-I-IFN and describe the demographic, clinical, and laboratory characteristics in a Moroccan cohort of patients with life-threatening COVID-19.

    We performed a cross-sectional and multicenter study of patients hospitalized in different university hospitals and clinical centers in Casablanca between November 2020 and December 2021.

    Our cohort included 195 patients with proven SARS-CoV-2 infection, 164 (84.1%) of whom developed severe or critical COVID-19 disease requiring hospitalization, and 31 (15.9%) patients developed mild or moderate disease. Patients with moderate or mild COVID-19 did not exhibit detectable levels of AAN-I-IFNs. Among the 20 patients with AAN-I-IFN, most were men (n=16, 80%), and age ranged from 19 to 101 years. 13 (65%) patients with severe COVID-19 and 7 (35%) with critical COVID-19 had AAN-I-IFNs. Twelve patients (60%) had autoantibodies (auto-Abs) neutralizing both high and low concentrations of IFN-α2 and/or IFN-ω, five (25%) had auto-Abs neutralizing only low concentrations of IFN-α2 or IFN-ω, two (10%) had auto-Abs neutralizing IFN-β (1ng/mL) only, and one (5%) had auto-Abs neutralizing high and low concentrations of IFN-α2 and IFN-ω, as well as IFN-β at 1ng/mL, but none neutralized IFN-β at 10 ng/mL.

    Overall, AAN-I-IFNs were detected in 20/195 (10.3%) of Moroccan patients with life-threatening COVID-19 and in 20/164 (12.2%) patients with severe or critical disease, whereas none were detected in patients with mild or moderate COVID-19.
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  • Anti-SARS-CoV-2 nucleoprotein IgA is associated with worse disease severity in critically ill COVID-19 pneumonia patients.
    3 days ago
    While humoral responses to vaccination and infection have largely focused on IgG, there is an evolving literature on ways in which IgA may drive neutrophil activity in lung injury secondary to viral infections, including COVID-19. We evaluated 238 immune-naïve, critically ill patients in the first year of the COVID-19 pandemic. Employing a laboratory-developed, multiplexed antibody testing, clinical history, medical record, and machine learning, we pursued relationships between systemic IgA and disease severity. Individuals with elevated anti-N IgA had 4-fold odds of more severe disease. This work emphasizes the importance of continued work to understand how different elements of the immune system participate together in contributing to patient outcomes.
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