Pneumocystis jirovecii causes life-threatening fungal pneumonia (PJP) and other serious pulmonary sequelae in HIV infected individuals and other immunocompromised populations. In recent years, while the frequency of PJP has declined in HIV infected individuals treated with anti-retroviral therapies, the incidence has increased among non-HIV populations due to the expanding use of corticosteroids and other immunomodulatory agents to treat immune-mediated inflammatory diseases and hematologic and solid malignancies. Despite the success of trimethoprim-sulfamethoxazole (TMP-SMX) prophylaxis, patients who are unable to tolerate treatment, take drugs where TMP-SMX is contraindicated, or experience breaks in daily compliance remain at risk. Immunocompromised populations would benefit from vaccine strategies that reduce morbidity and mortality due to acute PJP.

Herein, we used a newly established non-human primate (NHP) model of Pneumocystis infection in the context of drug-induced immunosuppression to test the immunogenicity and protective efficacy of a vaccine strategy administered prior to and throughout drug-induced immunosuppression using the 'pan-fungal' vaccine candidate NXT-2a. Longitudinal blood and bronchoalveolar lavage sampling was performed to monitor anti-NXT-2a antibody titers, lymphocyte populations, and infection status.

Immunization with NXT-2a prior to immunosuppression induced robust humoral immune responses in healthy outbred macaques. Subsequent therapeutic boosting throughout drug-induced immunosuppression prevented protective antibody titer decline. Our collective vaccination strategy provided significant protection against Pneumocystis infection throughout the duration of the study.

These studies demonstrate the efficacy and feasibility of an NXT-2a based vaccination strategy in a NHP model with a planned immunosuppressive regimen. This strategy may be further applied toward other opportunistic fungal pathogens, such as Candida spp. and Aspergillus spp. in similarly immunosuppressed populations.

With the inherent T-cell immunodeficiency of Schimke immune-osseous dysplasia (SIOD), the management of immunosuppressive therapy after transplantation and life-threatening infections remains a challenge. Here, we present a case of a child with SIOD who developed early-onset Epstein-Barr virus (EBV)-associated post-transplant lymphoproliferative disorder (PTLD) after kidney transplantation. PTLD frequently involves the gastrointestinal tract and solid allografts, while this case also involved the lungs, which is extremely rare. This case underscores the importance of considering PTLD in recipients with immunodeficiency, long-term immunosuppressive therapy, and EBV seronegativity. It also suggests low-dose immunotherapy and hematopoietic stem-cell transplantation for patients with SIOD.

Coronavirus disease 2019 (COVID-19) is known to induce gastrointestinal symptoms as well as respiratory symptoms. There have been instances where diarrhea persists after the acute phase of COVID-19, suggesting an extension of the disease's symptoms. It is not typical to recall the onset of inflammatory bowel disease (IBD) with such symptoms, much less with reports on Crohn's disease (CD). It is important to collect such cases in order to lead to appropriate diagnosis and treatment. This report presents a case of a young man in which diarrhea, initially manifesting during the acute phase of COVID-19, persisted for two months, ultimately leading to a CD diagnosis. At the onset of COVID-19, the patient had fever, abdominal pain, and diarrhea, but respiratory symptoms were not prominent. An ileocolonoscopy was performed to further investigate the cause of persistent diarrhea, leading to an appropriate diagnosis of CD. It is hypothesized that aberrations in the immune system triggered by severe acute respiratory syndrome coronavirus 2's impact on the intestinal tract might contribute to the onset of CD. The patient's condition gradually improved after the initiation of treatment with prednisolone. By the following treatment with azathioprine, the patient has maintained clinical remission. Clinicians should consider performing ileocolonoscopy for patients with persistent diarrhea after COVID-19, given the possibility of IBD. Gastrointestinal symptoms are relatively common with COVID-19. COVID-19 infection may trigger CD through immunological mechanisms. It is important to consider that cases of prolonged diarrhea after COVID-19 may include the induction of CD and to perform an ileocolonoscopy.

This study was aimed at determining whether stress echocardiography could detect exercise pulmonary hypertension (ePH) in patients with mild chronic thromboembolic pulmonary disease (CTEPD) as compared with right-heart catheterization (RHC).

Thirty-six symptomatic patients with persistent residual perfusion defects detected using ventilation/perfusion scintigraphy underwent a haemodynamic assessment by RHC and echocardiography at rest and during exercise. We compared pulmonary pressures in echocardiography with RHC values using the definitions in current ESC/ERS guidelines for ePH [mean pulmonary artery pressure/cardiac output (mPAP/CO) slope > 3 mmHg/L/min] and PH (mPAP > 20 mmHg).

Ten of the 36 patients (28%) exhibited an increase in the invasive mPAP/CO slope of > 3 mmHg/L/min. The correlation between echocardiographic and invasive measures of the mPAP/CO slope and systolic pulmonary pressure (sPAP) during peak exercise was ρ = 0.75 (95% C I = 0.53-0.97) and ρ = 0.75 (95% C I = 0.53-0.96), respectively. In bivariate logistic regression analyses, ePH was associated with the echocardiographic sPAP during peak exercise [o d d s  r a t i o (OR) = 1.13, 95% C I = 1.02-1.24] and with the echocardiographic mPAP/CO slope (OR = 3.86, 95% C I = 1.24-12.03). In ROC analysis, AUC was 0.89 (95% C I = 0.78-1.00) for the optimal exercise sPAP cut-off value of 56 mmHg (s e n s i t i v i t y = 90%, s p e c i f i c i t y = 87%), and 0.84 (95% C I = 0.66-1.00) for the optimal mPAP/CO slope cut-off value of 3.7 mmHg/L/min (s e n s i t i v i t y = 89%, s p e c i f i c i t y = 79%).

Stress echocardiographic assessments of the exercise sPAP and mPAP/CO slope predicted ePH as measured using RHC with good discrimination and acceptable calibration, providing promising evidence in diagnosing ePH in patients with CTEPD.

ClinicalTrials.gov identifier: NCT03405480.

Compartmental models are essential for studying host-pathogen dynamics, evaluating intervention effectiveness, and predicting infection trends. However, the utility of these models for testing competing hypotheses is often overlooked. To address this, we propose a new model-based hypothesis testing (MBHT) approach, which uses compartmental models to evaluate the hypotheses in epidemiology. In our case, using the COVID-19 pandemic as a case study, we formulate hypotheses of SARS-CoV-2 mutation and construct a transmission model to test them. In addition to analyzing steady-state stability, deriving the basic reproduction number, and identifying a backward bifurcation, the model is fitted to seven peaks of U.S. COVID-19 data, each corresponding to periods of viral mutation and morbidity peaks. The estimated posterior probabilities reveal that Short-term within host selection primarily shaped mutations during the early pandemic stages, followed by immune selection driven by natural and vaccine-induced immunity. In later stages, mutations aligned with vaccination-induced virulence and transmission-virulence correlation, while the declining virulence and immune selection partially explained the final stages of SARS-CoV-2 mutation. In conclusion, model-based hypothesis testing offers a powerful yet underutilized approach to uncovering drivers of viral mutation and gaining deeper insights into pathogen evolution during outbreaks.

The United States H5N1 outbreak which began in 2022 had widespread human health, animal health, and economic impacts. This outbreak led to the death or depopulation of over 175 million domestic birds and marked the first time that a highly pathogenic avian influenza (HPAI) virus was detected in cattle. Response to this emergency required coordination among various stakeholders in public health and agriculture sectors at federal, state, and local levels. Despite national and local efforts, a lack of trust between stakeholders diminished the efficiency of the response. The National Academies of Sciences, Engineering, and Medicine hosted a webinar featuring four experts in different agriculture sectors to gain their perspectives from the field on building trust during the H5N1 response. Their discussion highlighted the importance of proactive trust-building, communication and transparency, and incentives as catalysts to building trust in advance of a public health crisis. These insights are key for improving responses to future HPAI outbreaks and other health emergencies.

To identify the cardiac rehabilitation (CR) needs and preferences of women living in rural communities to inform the co-design of a women-focused web-based CR program.

Using a person-centred care and co-design approach, six 2-hour focus groups were conducted in-person or online across six rural regions of South Australia. Women with cardiovascular diseases who had completed a CR program were included. Discussions were directed using a semi-structured guide on the needs and preferences of women for different aspects of CR delivery. Data were transcribed verbatim, and thematic analysis was performed using NVivo.

Nineteen women (mean age 65.1 years, ±12.3) participated in one of six focus groups. Six key themes emerged: (1) Navigating financial barriers to care; (2) Early education and support matter; (3) Recognising women's heart health needs; (4) Empowering women through exercise and physical activity; (5) The power of connection: valuing professional and personal support; and (6) Integrating technology for accessible and flexible care.

Women expressed openness to using a web-based program to access and facilitate early CR participation. Tailored educational and exercise components, delivered through a financially viable model and supported by CR nurses, were identified as essential to meet the needs and preferences of women in rural areas. These findings provide critical insights for developing inclusive and sustainable CR programs that address the unique needs of women in rural settings.

Hip fracture (HF) is a common geriatric trauma resulting in a substantial rate of mortality and morbidity. Previous studies have shown that the application of leg compression significantly reduced the incidence of perioperative hypotension (PeH) and hypotension-related complication in obstetric surgery. The objective of this study was to evaluate the effect of medical compression stocking for prevention of PeH in elderly patients undergoing HF surgery.

Sixty patients were randomized in 2 groups: compression stocking (CS) group and no compression stocking (NCS) group (n = 30 each). Compression stockings were worn on the uninjured leg after spinal anesthesia and then removed after 24 h postoperatively. Demographic and perioperative data were collected. Primary outcome was the incidence of PeH measuring as 3 methods: intraoperative hypotension (IoH), postoperative hypotension (PoH), and concomitant intraoperative and postoperative hypotension (CoIPH). The secondary outcomes were the incidence of using intraoperative vasopressor and in-hospital hypotension-related complications related to hip fracture.

Baseline characteristics such as age, gender, diagnosis and operation were not significant difference between groups (p > 0.05 all). Regards the PeH, CS group demonstrated a significantly lower incidence in CoIPH than NCS group (0 patients vs. 6 patients, p = 0.02), and also showed a non-significantly lower incidence of the PoH and hypotension-related complication (p = 0.13 and 0.10, respectively). However, the IoH, and the need of intraoperative vasopressor did not significantly differ between both groups (p > 0.05 all).

The application of medical compression stocking in elderly patients undergoing HF surgery demonstrated an ability to reduce the incidence of hypotension perioperatively and might prevent in-hospital hypotension-related complication.

Coronary artery disease (CAD) is a leading cause of global cardiovascular morbidity and mortality, with a prevalence of 11% in Chinese adults and accounting for ~ 18 million annual deaths worldwide.

This study aimed to assess sleep quality and the degree of sleep apnoea in CAD patients after percutaneous coronary intervention (PCI) and identify key risk factors.

This multicentre, retrospective, case-control study was conducted at three tertiary centres in Changsha, China. Patients met the International Society of Cardiology and World Health Organization clinical diagnostic criteria, had CAD confirmed by angiography, had undergone PCI, and were stable. They were grouped by the Pittsburgh Sleep Quality Index. Sleep status and risk factors were analysed using univariate and multivariate analyses.

Among all 202 enrolled patients, univariate analysis showed significant differences between groups in gender (χ²=4.606, p = 0.032), age (63.38 ± 10.55 vs. 57.21 ± 9.37 years, t = 3.447, p < 0.001), maximum stenosis area (63.72% [56.98-66.49] vs. 57.46% [53.83-63.53], Z = - 4.919, p < 0.001), marital status (p = 0.025), smoking history (χ²=7.672, p = 0.006), alcohol history (χ²=9.640, p = 0.002), and tea drinking frequency (χ²=14.049, p = 0.007). Multivariate analysis indicated younger age (OR = 0.346, 95% CI:0.165-0.725, p = 0.005) and no alcohol history (OR = 0.420, 95% CI:0.187-0.944, p = 0.036) as protective factors, while less frequent tea drinking (OR = 2.758, 95% CI:1.223-6.224, p = 0.015) was a risk factor.

Sleep disturbances were present in 79.2% of post-PCI CAD patients. Age, alcohol consumption, and infrequent tea drinking were independent factors significantly associated with poor sleep quality.

Congenital heart disease (CHD) is frequently associated with extracardiac abnormalities that can significantly affect prognosis and management. Although abdominal ultrasound is a readily available and noninvasive tool, detailed observational studies on comprehensive screening for neonates with CHD remain lacking. We aimed to evaluate the prevalence of significant abdominal abnormalities detected during early comprehensive ultrasound screening in neonates with CHD. This single-center, retrospective case series included neonates admitted to a tertiary neonatal intensive care unit (NICU) between April 2021 and May 2024 who underwent screening within 14 days of birth. We compared the proportion of neonates with significant abnormalities and the number of abnormalities per patient between those with and without chromosomal abnormalities or malformation syndromes. Among 59 neonates, significant abnormalities were identified in 29 (49.2%). The most common were hydronephrosis (13.6%), hepatomegaly (10.2%), and intestinal malrotation (8.5%). The proportion of significant abnormalities did not differ significantly between the groups with and without chromosomal abnormalities or malformation syndromes (66.7% vs. 39.5%, P = 0.06). However, the number of abnormalities per patient was significantly higher in the former group (1.38 vs. 0.61, P = 0.03).

Early comprehensive abdominal ultrasound screening in hospitalized neonates with CHD revealed significant abnormalities in 49.2% of cases. This screening may improve systemic management of patients with CHD, including perioperative care, and facilitate individualized treatment of CHD‒with or without chromosomal or malformation syndromes‒by enhancing phenotype characterization.

・Congenital heart disease (CHD) is frequently associated with extracardiac abnormalities that can affect prognosis and management. ・Detailed observational studies on comprehensive abdominal ultrasound screening for neonates with CHD remain lacking.

・Early comprehensive abdominal ultrasound screening in hospitalized neonates with CHD revealed significant abnormalities in 49.2%. ・While abnormalities were more frequent in neonates with chromosomal or malformation syndromes, 39.5% of non-syndromic neonates had significant abnormalities; the screening improves systemic management and individualized treatment.