BACKGROUND COVID-19 significantly impacted the outcomes of patients, particularly those with comorbidities, including solid organ transplant recipients. The aim of this study was to investigate the incidence and mortality of COVID-19, as well as to identify independent risk factors associated with COVID-19-related death in patients undergoing orthotopic heart transplantation (OHT). MATERIAL AND METHODS The study followed 556 heart transplant recipients at a high-volume transplant center in Poland from March 2020 to March 2024. Patients were classified as infected based on a positive result from reverse transcription-polymerase chain reaction (RT-PCR) tests or SARS-CoV-2 antigen rapid tests performed on nasopharyngeal swab samples. RESULTS In the analyzed cohort, 189 of 556 patients (33.99%; 40 women, 21.16%) were diagnosed with COVID-19 following OHT. In total, 15 patients (7.94%) experienced recurrent SARS-CoV-2 infections, with 1 patient being diagnosed 3 times. A total of 33 patients (5.94%) required hospitalization due to COVID-19. Among the entire study cohort, 75 patients (13.49%) died, with 18 of these deaths (24%) directly attributable to COVID-19. In the multivariable analysis, vaccination against COVID-19 was identified as a protective factor against death due to the virus (OR, 0.22; 95% CI, 0.07-0.68; P=0.009) while increasing age was associated with a higher risk of mortality (OR, 1.08; 95% CI, 1.02-1.14; P=0.008). CONCLUSIONS The lack of COVID-19 vaccination and advanced age significantly influenced the COVID-19-related mortality risk.

Burnout among physicians is a growing concern, particularly during recent years in the setting of the Covid-19 pandemic. Recently, greater attention has been paid to researching physician burnout and its downstream effects (i.e. depression, suicidality); however, a majority of this research has focused on resident and attending physician populations. Medical students are a similarly vulnerable population, but the literature on medical student burnout is limited. Specifically, there is no existing literature that evaluates the trend of medical student burnout over recent years, particularly since the Covid-19 pandemic-a time when students navigated challenges related to their clinical experiences and virtual coursework. The aim of this study is to better understand the prevalence of feelings of burnout among American medical students, and evaluate the trend since the mid-2010s. Further, this study aims to compare average burnout scores among 2nd and 4th year medical students, to analyze the relationship between academic year and feelings of exhaustion and disengagement. We analyzed national data collected from the American Association of Medical Colleges' Year Two and Graduation Questionnaire, each of which includes an Oldenburg Burnout Inventory for Medical Students. We found that since 2014, levels of reported exhaustion have significantly increased among medical students. We also found that between 2nd and 4th year students, the 4th year students have consistently reported lower levels of burnout than their 2nd year counterparts over time. Finally, we also found that burnout scores peaked among 2nd year medical students at the time of the Covid-19 pandemic, and have since trended down. These findings provide an essential understanding of burnout trends among American medical students, and can be utilized to help medical educators plan the timing and objectives of wellness interventions.

Unpaid caregivers-those who provide essential support to family, friends, or neighbours with disabilities, chronic conditions, mental health, or other health concerns-play a critical role in sustaining Canada's health and social systems. Despite their significant contributions, caregivers remain undervalued, under-recognized, and under-supported. This marginalization has led to elevated rates of burnout, mental health distress, and financial strain, disproportionately impacting women and racialized populations. The COVID-19 pandemic further revealed the systemic risks and potential harms of excluding caregivers from care environments (e.g., hospitals, long-term care settings), prompting urgent calls for reform. This Photovoice study forms part of a broader four-year research program engaging caregivers from diverse communities to co-develop evidence and advocacy tools to support best practices in healthcare for engaging caregivers and inform a new Research and Innovation Hub focused on caregiving.

Using a community-based participatory research (CBPR) approach, a series of Photovoice workshops will be conducted with four priority caregiver groups in Peel Region, Ontario: (1) caregivers of children with complex care needs; (2) caregivers of seniors; (3) caregivers supporting young adults with mental health challenges; and (4) women caregivers supporting multiple generations. Each group will participate in six virtual workshops focused on photo taking, narrative development, collaborative theming, and advocacy planning. The study foregrounds caregivers as co-researchers, not just participants, and integrates inclusive research practices including compensation, ongoing consent, check-ins, and other supports throughout the process. Data will be collaboratively analyzed with participants to identify cross-cutting themes and policy and practice recommendations. A follow-up qualitative evaluation will assess co-researcher participants' experiences with the method and its impact.

This study centers caregiver perspectives, experience, and expertise to inform responsive health system change. Employing CBPR and Photovoice principles will help to amplify caregiver voices and generate actionable knowledge aimed at addressing structural inequities in caregiving policy and practice.

Boolean networks are powerful frameworks for capturing the logic of gene-regulatory circuits, yet their combinatorial explosion hampers exhaustive analyses. Here, we present a systematic reduction of a published 31-node Boolean model that describes cisplatin- and pemetrexed-resistance in non-small-cell lung cancer to a compact 9-node core that exactly reproduces the original attractor landscape. Through a sequence of biologically guided reductions (31→29→14→9 nodes), the streamlined network shrinks the state space by four orders of magnitude, enabling rapid exploration of critical control points, rules fitting, and candidate therapeutic targets. Extensive synchronous and asynchronous simulations, combined with a Boolean rule-fitting algorithm that removes spurious limit cycles, confirm that the three clinically relevant steady states and their basins of attraction are conserved and reflect resistance frequencies close to those reported in clinical studies. The reduced model provides an accessible scaffold for future mechanistic and drug-discovery studies.

Next-generation sequencing (NGS) is essential for precision oncology, yet its clinical implementation is often hindered by limited sample quantity, complex workflows, and cross-contamination risks. We evaluated a modified One-Step Multiplex PCR (OS-MPCR) assay designed to streamline library construction while maintaining high analytical sensitivity and diagnostic accuracy.

The OS-MPCR method integrates adapter ligation and library amplification into a single, closed-tube reaction, eliminating intermediate open-tube manipulations. The analytical performance was evaluated using standard reference materials targeting SNVs, Indels, and fusions. Clinical validation was performed on retrospective formalin-fixed paraffin-embedded (FFPE) specimens (DNA, N = 76; RNA, N = 34) from lung cancer patients, using well-established liquid-phase hybrid capture assays as the clinical verification standard.

OS-MPCR streamlined the workflow, reducing hands-on time to just 20 minutes. The assay enabled reliable variant detection at 1% frequency with as little as 1 ng of DNA for SNVs/Indels and 5 ng of total RNA for fusions, with low-input quantification limits inherently bounded by absolute molecular copy numbers. In the clinical cohort, OS-MPCR demonstrated 100% diagnostic concordance with the verification method. Quantitative analysis revealed a strong correlation in variant allele frequencies (Spearman r = 0.9777, 95% CI: 0.9668-0.9851, P < 0.0001), with libraries consistently achieving highly reproducible yields and stable, near 1.0 target rates across the entire cohort.

OS-MPCR offers a streamlined and low-input alternative to conventional multi-step multiplex PCR methods. By combining reduced hands-on time and intrinsic contamination control with high analytical accuracy, this approach represents a practical refinement for targeted amplicon sequencing in diagnostic workflows.

Additional treatment options are needed for patients with hospital-acquired and ventilator-associated bacterial pneumonia (HABP/VABP) caused by carbapenem-resistant pathogens. This subgroup analysis examined clinical and microbiologic outcomes in participants from RESTORE-IMI 2 treated with imipenem/cilastatin/relebactam (IMI/REL), stratified by baseline lower respiratory tract (LRT) isolate susceptibility to imipenem. Emergence of nonsusceptibility to IMI/REL during treatment was also evaluated.

Baseline LRT specimens were obtained ≤48 hours before screening, identified at a central laboratory, and susceptibility determined per the Clinical and Laboratory Standards Institute breakpoints. Outcomes for participants who received IMI/REL, with ≥1 imipenem-nonsusceptible, imipenem/REL-susceptible baseline LRT pathogen were compared with participants with imipenem-susceptible pathogens. Emergence of nonsusceptibility to imipenem/REL was also assessed, and isolates were characterized molecularly.

In total, 215 participants in the microbiologic-modified intent-to-treat population received IMI/REL, of whom 112 were infected with imipenem-susceptible pathogens and 18 with imipenem-nonsusceptible, imipenem/REL-susceptible pathogens and were included in this analysis. Of these 18 participants, 88.9% were in the intensive care unit and 83.3% had one gram-negative baseline pathogen. Day 28 all-cause mortality was 22.2% and 18.8% (adjusted difference: 7.3 [-8.8 to 31.1]) for participants who received IMI/REL for the treatment of HABP/VABP caused by imipenem-nonsusceptible versus imipenem-susceptible pathogens, respectively. Of a total of 192 isolates, 59 gram-negative isolates (baseline isolates that were nonsusceptible to imipenem and subsequent isolates of the same species from the same participants) were characterized using multiplex polymerase chain reaction and sequencing techniques. Emergence of nonsusceptibility to imipenem/REL occurred in isolates from three of the 112 participants with indicated imipenem-susceptible baseline pathogens (two isolates of Pseudomonas aeruginosa and one isolate of Klebsiella pneumoniae).

Day 28 all-cause mortality was similar among participants treated with IMI/REL, regardless of baseline pathogen susceptibility to imipenem. Emergence of nonsusceptibility to imipenem/REL on treatment was low.

ClinicalTrials.gov (NCT02493764).

Lung infections with opportunistic pathogens, such as Pneumocystis or Nocardia, are infrequent in patients with severe asthma despite the use of high doses of inhaled or oral corticosteroids. We report two patients with severe eosinophilic asthma complicated by Nocardia infection in the respiratory tract. Both patients had exposure to chronic corticosteroid therapy and developed recurrent respiratory infections. The first patient had nodular pulmonary nocardiosis associated with hypocomplementemia and heterozygous variants in C1QB and NOD2, while the second patient had Nocardia farcinica tracheobronchitis, associated with selective immunoglobulin M reduction, and a heterozygous F508del mutation in the CFTR gene. Following appropriate antibiotic therapy and immunoglobulin replacement, both patients experienced fewer respiratory infections and stable pulmonary function. These cases highlight that opportunistic infections like Nocardia can occur in severe asthma under chronic immunosuppression, emphasizing the need for thorough immunologic evaluation and vigilant infection monitoring.

Highly pathogenic (HP) H5N1 avian influenza viruses are zoonotic pathogens and are endemic in wild birds and poultry around the world. Pro-inflammatory cytokines are supposed to contribute to the severe clinical symptoms in infected animals and humans. In this study, we determined the infectivity and cytokine induction in primary human lung cells infected with HP H5N1 avian influenza viruses and seasonal H3N2 influenza viruses. MDCK cells were used to measure viral titers in the supernatants of infected human lung cells by log10TCID50/ml. Quantitative real-time PCR was used to detect the induction of cytokine genes using mRNA from the infected primary human lung cells. HP H5N1 avian influenza viruses induced higher viral titers than seasonal H3N2 influenza viruses in supernatants of primary human lung cells. In addition, HP H5N1avian influenza viruses induced the genes of pro-inflammatory cytokines such as IL-23, IL-1α, IL-1β, IL-6, and IL-8 at significantly higher levels than seasonal H3N2 influenza viruses in primary human lung cells. Our data suggest that the high viral replication and the high induction of pro-inflammatory cytokines in the human lung cells infected with HP H5N1 avian influenza viruses may enhance pathogenicity in the infected humans as compared to seasonal H3N2 influenza viruses.

Inherited metabolic disorders (IMDs) are uncommon but clinically important causes of respiratory morbidity in children. Respiratory involvement may be the first or dominant manifestation, although it may precede, accompany, or follow systemic involvement. Because cough, dyspnea, hypoxemia, recurrent infection, abnormal chest imaging, and ventilatory failure are non-specific, affected children may initially be managed for common respiratory conditions, such as infection, asthma, aspiration, immunodeficiency, or non-metabolic diffuse lung disease, before the underlying IMD is recognized. This narrative mini-review presents a phenotype-driven approach to recognizing IMDs in pediatric respiratory practice. Rather than cataloguing rare disorders by metabolic pathway, it organizes respiratory involvement into practical clinical entry points: diffuse lung disease, pulmonary alveolar proteinosis-like disease, pulmonary vascular disease, recurrent infection or bronchiectasis, upper-airway or thoracic restriction, and neuromuscular respiratory failure and aspiration. For each pattern, we highlight extrapulmonary red flags and first-line biochemical, enzymatic, and genetic tests that may guide early etiological diagnosis.

Careful recognition of respiratory phenotypes, combined with targeted metabolic and genomic evaluation, may shorten diagnostic delay and allow disease-specific treatment before irreversible pulmonary or neurological injury occurs.

• IMDs can involve the respiratory system and may mimic common pediatric respiratory disorders or non-metabolic forms of childhood diffuse lung disease. • Respiratory manifestations may precede, accompany, or follow classical systemic features, and their temporal pattern varies among individual IMDs.

• This mini-review organizes IMD-related respiratory involvement by presenting respiratory phenotype rather than by metabolic pathway. • It links respiratory entry points with extrapulmonary red flags and targeted biochemical, enzymatic, and genetic testing to support earlier diagnosis.

Accurate interpretation of high-risk acute coronary syndrome (ACS) electrocardiograms (ECGs) is essential for early diagnosis and timely reperfusion, yet substantial deficits persist across health care professions. Digital self-learning formats such as FOAMed (Free Open Access Medical Education) are widely used, but their effectiveness has rarely been evaluated for complex, high-risk ACS ECG patterns. Existing ECG education studies often focus on students or single professional groups and established ST-segment elevation myocardial infarction (STEMI) criteria, leaving newer guideline-recognized STEMI equivalents, selected emerging occlusion myocardial infarction (OMI)-related patterns, and interprofessional emergency care underrepresented.

This study aimed to compare the effectiveness of FOAMed podcast and videos versus traditional print-based materials for teaching high-risk ACS ECG patterns and related clinical decision-making in emergency providers.

We conducted a prospective, interprofessional, controlled mixed methods trial across 5 training sites in Germany. Paramedics, prehospital emergency physicians, and emergency department clinicians received either a FOAMed multimedia module or print-based materials through concealed allocation; deviations from the intended 1:1 ratio resulted from participant no-shows. The intervention consisted of a 30-minute supervised self-learning session. In total, 103 participants were allocated to FOAMed (n=45) or print-based materials (n=58). Two coprimary outcomes were assessed: ECG interpretation accuracy and text-based ACS clinical decision-making. Secondary outcomes included subjective confidence, learning experience, and exploratory qualitative free-text responses. Outcome assessment was automated and blinded; mixed ANOVA was the primary analysis. The study was not prospectively registered because it assessed educational outcomes in health care professionals rather than patient health outcomes.

All 103 participants completed the study. Both groups improved, with greater gains in the FOAMed group: ECG interpretation increased from 55% to 65.5% and text-based ACS clinical decision-making from 45% to 68%, versus 57% to 60% and from 47% to 63%, respectively, in the print-based group. Effect sizes were η²=0.055 for ECG interpretation and η²=0.044 for clinical decision-making. Exploratory subgroup analyses provided no evidence of differential effects across age, gender, or professional background and were likely underpowered. Qualitative responses (46 and 37 entries) provided contextual insights into perceived clarity, engagement, and practical relevance supporting the quantitative findings.

This study is innovative in directly comparing a curated FOAMed multimedia module with selected print-based materials in an interprofessional emergency care population. It differs from existing research by focusing on subtle, emerging ischemic patterns and evaluating realistic, time-limited self-learning formats. The findings provide evidence that curated FOAMed resources can produce greater short-term improvements in ECG interpretation and text-based ACS clinical decision-making than traditional print-based materials in this setting. Although implications for clinical performance remain hypothetical, concise, high-quality digital modules may represent a practical supplement to structured continuing education in emergency care.