• Exposure to per-and polyfluoroalkyl substances and early-onset cancers.
    1 week ago
    Environmental exposures, such as per-and polyfluoroalkyl substances (PFAS), are suspected to play a role in the significant increase in incidence of some early-onset cancers. PFAS are chemicals of concern due to their persistence in the environment, long biological half-lives, and potential carcinogenic properties. Exposure during sensitive windows of development may exert durable effects on cancer-related biological pathways leading to greater risks of early-onset cancers. This review summarizes the current evidence of PFAS exposure and early-onset carcinogenesis, with an emphasis on potential exposure routes, early-onset cancer development in humans linked with PFAS exposure, and mechanistic pathways. Emerging evidence supports a potential role for PFAS exposure in carcinogenesis during early life, particularly through prenatal and early postnatal windows of susceptibility. While epidemiologic studies increasingly link PFAS to several types of cancer, the evidence specifically addressing early-onset cancers remains limited and heterogeneous. Future research should prioritize prospective, longitudinal cohort studies with repeated exposure measurements spanning prenatal, infancy, and childhood periods, coupled with long-term follow-up into early adulthood to capture early-onset cancer outcomes.
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  • Preoperative Carriage of Respiratory Viruses and Acute Respiratory Distress Syndrome After Cardiac Surgery: Protocol for the VIRUS-ATTAC Prospective Cohort Study.
    1 week ago
    Cardiac surgery patients are at particular risk of postoperative acute respiratory distress syndrome (ARDS), with an estimated incidence of 5% to 10%. Cardiopulmonary bypass (CPB), ischemia-reperfusion injury, and blood product transfusions are well-recognized contributing factors. Asymptomatic carriage of respiratory viruses has been hypothesized to prime the lungs and potentiate ARDS development when combined with the pulmonary insults of cardiac surgery. However, no study has directly assessed the relationship between preoperative asymptomatic viral carriage and postoperative ARDS.

    The VIRUS-ATTAC study aims to determine whether asymptomatic carriage of influenza or other respiratory viruses is independently associated with postoperative ARDS following elective cardiac surgery under CPB.

    VIRUS-ATTAC is a prospective, multicenter, low-interventional clinical study conducted across 5 French university hospitals and sponsored by Rennes University Hospital. Adult patients scheduled for elective cardiac surgery under CPB are eligible. A nasopharyngeal flocked swab is collected at anesthesia induction and tested using a multiplex reverse transcription polymerase chain reaction assay detecting 16 respiratory viruses. Results are kept blinded to the clinical team. The primary outcome is ARDS within 7 postoperative days, defined using the Berlin criteria and adjudicated by an independent blinded committee. Secondary outcomes include reintubation, postoperative pulmonary complications, pneumonia, ventilator-free days, intensive care unit-free days, hospital-free days, and 28-day mortality. The primary analysis uses a causal inference framework with a directed acyclic graph for confounder selection and g-computation to estimate the average treatment effect of viral carriage on ARDS risk. A sample size of 1250 patients (including 250 asymptomatic influenza carriers) provides 80% power to detect a 5% absolute risk increase in ARDS (2-sided α=.05).

    The VIRUS-ATTAC study received ethics approval from the Comité de Protection des Personnes Sud-Est VI, and recruitment was initiated in February 2021 across 5 French university hospitals. Data collection was completed on March 10, 2023. Of the 1258 patients assessed as eligible, 1204 provided written informed consent and were enrolled. The study database was locked on April 9, 2026. Statistical analysis began after database lock, and the results are expected to be reported in a separate publication in 2027.

    VIRUS-ATTAC is the first prospective multicenter study to directly evaluate the association between preoperative asymptomatic respiratory viral carriage and postoperative ARDS in cardiac surgery patients. If confirmed, this association would provide a rationale for evaluating preventive strategies, such as systematic preoperative vaccination or postponement of elective surgery in carriers, in future interventional studies aiming to reduce postoperative respiratory complications.
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  • Factors associated with the development of neonatal acute respiratory distress syndrome in preterm infants: a retrospective cohort study.
    1 week ago
    Neonatal acute respiratory distress syndrome (NARDS) carries high morbidity and mortality. Preterm infants at risk need to be identified early so that treatment is not delayed. We aimed to identify factors associated with NARDS in preterm infants. Clinical data of 548 preterm infants admitted to the NICU between 2019 and 2023 were retrospectively analyzed. Preterm infants were categorized into the NARDS group (n = 275) and the control group (n = 273) according to the Montreux definition. Univariate analysis and multivariable logistic regression were used to identify factors independently associated with NARDS; the results are shown in a forest plot. The study was reported in accordance with the STROBE guidelines. Six factors were independently associated with NARDS in preterm infants: male sex (OR = 1.895, 95% CI 1.051-3.420), premature rupture of membranes (PROM) (OR = 6.784, 95% CI 3.415-13.478), chorioamnionitis (OR = 11.143, 95% CI 5.460-22.742), cesarean delivery (OR = 2.104, 95% CI 1.125-3.935), higher PaCO2 (OR = 1.188 per mmHg, 95% CI 1.143-1.234), and lower gestational age (OR = 0.715 per week, 95% CI 0.587-0.871).

    Male sex, lower gestational age, PROM, chorioamnionitis, cesarean delivery, and elevated early postnatal PaCO2 were independently associated with NARDS in preterm infants. All six are available in routine practice and could help clinicians flag preterm infants who need closer monitoring.

    • NARDS is a severe, recently defined form of acute respiratory failure in neonates, and evidence on its risk factors in preterm infants remains limited.

    • Male sex, lower gestational age, premature rupture of membranes, chorioamnionitis, cesarean delivery, and elevated PaCO2 within 15 min of birth were independently associated with NARDS in preterm infants.
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  • Prevalence and determinants of antimicrobial resistance in pneumonia among adult patients in Hospital Shah Alam, Malaysia.
    1 week ago
    Antimicrobial resistance (AMR) continues to threaten our healthcare system. Unnecessary antibiotic use contributes to the development of AMR infections in hospitalized pneumonia patients. This study was conducted to determine the prevalence of AMR and its associated factors in pneumonia among adult patients treated in-patient in a hospital.

    A cross-sectional study was conducted using data extracted from the hospital's electronic medical records. Patients aged 18 years or older admitted to the hospital from 1st January 2018 to 31st December 31 2023, discharged with a diagnosis of pneumonia were included in the study population.

    A total of 300 eligible samples were selected using universal sampling. The analysis revealed a prevalence of AMR of 15.7% (95% CI: 11.5, 19.8). Multivariable analysis using multiple logistic regression showed that patients' age (OR = 1.03; 95% CI: 1.01, 1.05), Indian and other ethnicities (OR = 2.24; 95% CI: 1.05, 4.77), length of stay (OR = 1.05; 95% CI: 1.01, 1.08) and invasive procedures (OR = 3.65; 95% CI: 1.71, 7.82) were significantly associated with AMR.

    The findings from our study highlighted a considerable burden of AMR among pneumonia patients in a Malaysian tertiary hospital. Thus, there is a need for targeted infection control strategies and antimicrobial stewardship, especially among high-risk groups. Strengthening surveillance and justified antibiotic use is crucial to fight the rising threat of AMR in Malaysia.
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  • Socioeconomic and Demographic Influences on Biologic Treatment Outcomes in Patients With Chronic Rhinosinusitis.
    1 week ago
    Chronic rhinosinusitis with nasal polyps (CRSwNP) is a prevalent inflammatory disease that significantly impairs quality of life (QOL) and imposes a substantial economic burden. Socioeconomic and demographic factors influence access to care, treatment adherence, and outcomes, yet their impact on response to biologic therapy remains poorly defined.

    To examine the impact of socioeconomic and demographic determinants on symptom severity and QOL before and after monoclonal antibody therapy for CRSwNP.

    Exploratory retrospective cohort study with prospective socioeconomic and demographic data curation.

    Tertiary medical center.

    Adults with recalcitrant CRSwNP from January 2020 to January 2024 who had undergone endoscopic sinus surgery and completed a 16-week regimen of monoclonal antibody therapy.Intervention or Exposures:The primary exposures evaluated were socioeconomic status (SES; including household income) and demographic determinants.

    Baseline and post-treatment (16 weeks) follow-up of 22-item Sino-Nasal Outcome Test (SNOT-22) and Meltzer grading evaluation.

    Forty patients (21 males and 19 females; mean age 50.4 ± 12.1) were included. The mean baseline SNOT-22 score was 69.0 ± 15.8, and the median Meltzer score was 3 (interquartile range [IQR]: 2-3.75). At 16-week follow-up, these scores improved to 33.8 ± 20.5 and 1 (IQR: 0-2), respectively. Low-income patients (<40 000 United States Dollar [USD] yearly) had worse baseline SNOT-22 scores compared to medium (40 001-80 000 USD yearly) and high-income patients (>80 000 USD yearly; 79.4 vs 68.6 vs 57.1, respectively, P < .01) but showed the largest absolute point reduction (ΔSNOT-22, 47.8 vs 34.7 vs 20.8, respectively, P = .01). Low-income patients showed the largest absolute improvement after biologic treatment (P = .01); however, covariate adjustment for baseline scores showed similar proportional effects across all income tiers.

    Patients with lower incomes exhibited higher baseline disease severity. However, biologic treatment yielded meaningful absolute improvement in QOL across all SES tiers.

    Recognizing socioeconomic factors may help optimize biologic therapy in CRS. Future multi-center research is needed to validate these disparities and optimize intervention strategies.
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  • Excessive Stretch of Airway Smooth Muscle (but Not Epithelial) Cells Activates Paracrine TGF-β1 to Induce Smad2-Mediated G1 Arrest in Airway Epithelial Cells.
    1 week ago
    Although mechanical ventilation (MV)-associated excessive stretch directly damages airway epithelial cells (AECs) and contributes to ventilator-induced lung injury (VILI), the contribution of paracrine factors from airway cells, particularly airway smooth muscle cells (ASMCs) and AECs, remains poorly understood. As stretch-sensitive cells, ASMCs and AECs may respond to excessive stretch by secreting paracrine factors such as transforming growth factor β1 (TGF-β1), thereby disrupting airway epithelial integrity. This study compared the sensitivity of cultured ASMCs and AECs to MV-associated excessive stretch and their ability to induce paracrine factors, particularly TGF-β1, that inhibit AEC proliferation in vitro.

    Human ASMCs and AECs (16HBE14o-) were cultured under static, physiological stretch (5% strain), or pathological excessive stretch (13% strain) conditions for 72 h. Conditioned media were collected and used to culture 16HBE14o- cells for 48 hours. Active and total TGF-β1 levels in the conditioned media were measured using an enzyme-linked immunosorbent assay. Cell viability, proliferation, migration, stress fiber formation, cell cycle distribution, and Smad2 signaling were assessed using the Cell Counting Kit-8 assay, cell counting, wound healing assay, immunofluorescence, flow cytometry, quantitative reverse transcription polymerase chain reaction, and Western blotting, respectively.

    Conditioned media derived from ASMCs, but not 16HBE14o- cells, cultured under 13% excessive stretch inhibited 16HBE14o- cell proliferation. In addition, excessive stretch enhanced TGF-β1 activation in ASMCs in an integrin αV-dependent manner. Experiments using a TGF-β1-neutralizing antibody and transforming growth factor β receptor I inhibitors demonstrated that inhibition of 16HBE14o- cell proliferation by conditioned media derived from excessively stretched ASMCs was dependent on TGF-β1 activation and Smad2 signaling.

    Conditioned media derived from ASMCs, but not AECs, exposed to MV-associated excessive stretch induced G1 cell cycle arrest in AECs via TGF-β1/Smad2 signaling. These findings suggest that ASMCs are more sensitive than AECs to excessive stretch-induced TGF-β1 activation and may thereby contribute to disruption of airway epithelial integrity. Targeting this paracrine pathway may warrant further investigation as a potential strategy for preventing or treating VILI.
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  • Outcome of Unilateral Transverse Cordotomy or Kashima Operation for Bilateral Vocal Cord Immobility.
    1 week ago
    Endoscopic laser cordotomy, also known as Kashima operation, is used for the treatment of bilateral vocal cord palsy where the glottis chink is made posteriorly, sufficient enough for patient to breathe comfortably without any stridor. The objective of the study was to assess outcome of unilateral transverse cordotomy (Kashima operation) for bilateral vocal cord immobility. This prospective observational study was conducted in the Department of Otolaryngology-Head & Neck Surgery, Bangladesh Medical University, Dhaka, Bangladesh from January 2020 to June 2021 with 12 patients having bilateral vocal cord immobility with shortness of breath (SOB) or tracheostomized for SOB due to bilateral vocal cord immobility. The diagnosis was confirmed by fiberoptic laryngoscopy. Endoscopic assessment of subglottis and trachea was also done for assessment of any co-incidental pathology which may affect the outcome. Outcome of the surgery was evaluated by Flow volume loop Spirogram, Medical Research Council Dyspnoea Scale (MRCDS) 2007 and Voice Handicap Index (VHI) scores. All the information were recorded in a pretested questionnaire. The mean ±SD preoperative MRCDS was 4.33±0.49 and mean postoperative MRCDS was 1.75±1.06, 1.50±0.80 and 1.33±0.6 at 1st, 2nd and 3rd months of follow-up respectively. Mean ±SD preoperative total VHI score was 24.50±2.11 and postoperative score was 75.50±25.57, 44.17±31.50 and 37.33±22.86 at 1st, 2nd and 3rd months of follow-up respectively. MRCDS was significantly improved after Kashima operation (p<0.001). But no significant difference was observed in pre and at 3 months postoperative VHI score (p>0.05). In this study, preoperative mean of FVC, PEFR, PIFR, FEF50% and FIF50% were found 1.7±0.09 L, 2.5±0.12 L/S, 1.75±0.11 L/S, 0.84±0.06 and 2.08±0.38 respectively. Postoperative means of FVC, PEFR, PIFR, FEF 50% and FIF 50% were found 2.5±0.12 L, 4.5±0.12 L/S, 3.54±0.54 L/S, 1.84±0.40 and 3.54±0.69 at follow-up period of 2 months respectively. Statistically significant differences were observed in between pre and postoperative all the parameters of spirometry (p<0.001). In this study, only 2(16.67%) cases were developed complications after surgery. Vocal cord oedema in 1(8.33%) case and Fibrosis with granuloma in 1(8.33%) case. Kashima procedure is an effective surgery to reduce the severity of dyspnoea in bilateral vocal cord immobility without significant change of voice.
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  • Experiences of healthcare access during the COVID-19 pandemic in remote Indigenous communities in Northwest Territories, Canada.
    1 week ago
    The COVID-19 pandemic disrupted healthcare access globally through restrictions aimed at limiting virus transmission. Using a cross-sectional design, this project explored perceived barriers to and facilitators of healthcare access during the pandemic in remote Indigenous communities in Northwest Territories (NWT), Canada. Convenience sampling was utilised to recruit self-identifying Indigenous adults (≥18 years) within 10 NWT communities. Information was collected through an interviewer-administered questionnaire exploring experiences with, barriers to, and facilitators of healthcare access during the COVID-19 pandemic. Among the 287 participants (mean age 41.63 years; 66.55% women), 17.42% reported having avoided healthcare service utilisation during COVID-19 due to the risk of exposure. Of participants with a current prescription, 15.73% reported difficulty accessing prescription medications. Some partcipants (7.69%) reported difficulty accessing traditional medicines and healers. The participants reported that many services were disrupted by shortages of healthcare providers, service delays and cancellations, public health measures, and medical travel disruptions. A total of 35.89% of participants utilised virtual care, and while many found it was convenient for certain needs, some reported that it was inadequate. The findings highlight the perceived challenges to healthcare access in NWT during the pandemic. These challenges are closely tied to the healthcare context in the region, which depends heavily on medical travel and visiting specialist clinics.
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  • Real-world evaluation of 2023-2024 XBB.1.5 mRNA and protein-based COVID-19 vaccine reactogenicity from the randomized BEEHIVE trial.
    1 week ago
    The objective of this analysis was to assess reactogenicity profile differences between a protein- and mRNA-based COVID-19 vaccine in participants who had previously received ≥2 doses of an mRNA-based vaccine in a real-world, double-blinded, randomized, controlled trial. In the BEEHIVE/NCT06065176 trial (ClinicalTrials.gov: NCT06065176), participants randomized 1:1 received one dose of the Novavax (NVX) or Pfizer-BioNTech (PFZ) COVID-19 vaccine 2023-2024 formulation (XBB.1.5); a comparator group did not receive a dose. Electronic surveys collected solicited systemic (fatigue, fever, headache, joint pain, malaise/feeling sick, muscle pain, and nausea/vomiting) and local (injection-site pain, tenderness, and swelling) events on days 1, 2, and 6 after study vaccination. Significantly lower proportions of participants in the NVX (n = 448) vs. PFZ (n = 453) group reported a systemic (62.1% vs. 75.7%; risk difference -13.7%, 95% CI: -19.6% to -7.7%) or local (81.0% vs. 92.7%; risk difference -11.7%, 95% CI: -16.0% to -7.3%) event in the day-1 survey (both Cochran-Mantel-Haenszel P < .0001). Most events were mild. Reactogenicity rates decreased throughout the week; >80% and >94% of participants in either group reported no systemic or local reactogenicity, respectively, in the day-6 survey. Mean number of events/person were significantly lower for the NVX vs. PFZ group in the day-1 (systemic and local) and day-2 (local) surveys (each P < .0001). There were significant differences in reactogenicity profiles for the 2023-2024 formulations of the NVX and PFZ COVID-19 vaccines, with NVX consistently associated with lower reactogenicity rates than PFZ.
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  • Quantifying the direct and indirect impact of COVID-19 vaccination: evidence from Victoria, Australia.
    1 week ago
    Vaccines not only directly protect vaccinated individuals but also contribute to protecting the entire population via indirect herd-immunity benefits. However, researchers have long struggled to quantify these indirect effects at the population level, hindering the assessment of vaccination programme effectiveness. We developed a new method to estimate these effects, thereby markedly improving measures of the number of infections, hospitalizations and deaths averted by vaccination. Our population-based analysis of 6 440 000 residents of Victoria, Australia, reveals strong indirect effects during the Delta outbreak (September-November 2021). By modelling a non-vaccination counterfactual, we conservatively estimate 315 000 infections were averted (95% Bayesian credible interval (BCI): 231k-406k), as well as 33 400 hospitalizations (95% BCI: 22k-46k), and 4900 deaths (95% BCI: 2.8k-7.2k). These are 4.0, 7.5 and 8.0 times higher, respectively, than observed. Half of the averted infections and around one-quarter of hospitalizations and deaths were attributable to indirect protection. Homogeneous vaccination across local government areas could have reduced outcomes by approximately 25%.
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