COVID-19 mRNA vaccines have been reported to reduce severe COVID-19 outcomes in high-risk populations. In Japan, booster vaccinations up to the seventh dose are publicly funded; however, evidence regarding the safety and potential benefits of repeated booster doses in younger adults remains limited. This exploratory observational study aimed to describe age-specific patterns of all-cause mortality according to the number of COVID-19 vaccine doses using municipal administrative registry data.

Municipal registry data obtained through information disclosure requests from Hamamatsu City (2021-2024) and Matsudo City (2021-2025) were analyzed. The dataset included age group or year of birth (5-year increments), sex, date of residence, COVID-19 vaccination records (date and lot number), and date of death. Individuals aged 20-89 years were categorized into three age groups (20-49, 50-64, and 65-89 years). All-cause mortality rates were calculated per 100,000 person-years according to the number of vaccine doses. Exploratory comparisons between dose groups were conducted using Poisson tests. Because the registry dataset lacked information on comorbidities, healthcare utilization, socioeconomic status, and cause of death, multivariable adjustment and causal inference were not feasible.

Age-specific differences in all-cause mortality rates were observed across vaccine dose groups. Among individuals aged 65-89 years, higher numbers of vaccine doses were associated with lower all-cause mortality rates. In contrast, among those aged 20-49 years, all-cause mortality rates were higher among individuals who had received ≥5 doses than among those who had received fewer doses. Among individuals aged 50-64 years, the all-cause mortality rate was higher among those who had received six doses than among those who had received 1, 3, or 4 doses.

This exploratory analysis identified age-specific differences in all-cause mortality across COVID-19 vaccine dose groups. However, the dataset available so far lacked important clinical covariates and information on causes of death, limiting causal interpretation. These findings highlight the need for constructing in Japan nationally linked datasets that allow adjustment for comorbidities, healthcare utilization, and other potential confounders.

This study aims to screen indicators for predicting the occurrence of refractory Mycoplasma pneumoniae pneumonia (RMPP) in children, determine the combined factors for predicting RMPP, and provide a basis for the early identification of children with RMPP and the determination of treatment plans.

This study was a retrospective case-control analysis. A total of 522 children with MPP and 28 clinical indicators were included. Clinical feature, hospitalization period, laboratory data, etc., were collected. The risk factors related to RMPP were screened through univariate analysis. A multivariate logistic regression model was established, and stepwise regression was used to screen out independent risk factors. The operating characteristic curve (ROC) of the combined predictor was drawn for predictive efficacy analysis. A visual nomogram model for predicting the probability of RMPP occurrence was constructed and validated.

Differing from other results, there were no statistically significant differences in demographic indicators such as age and gender between the two groups. The multivariate logistic regression analysis showed that duration of fever (OR = 1.407), PLT (OR = 0.997), pleural effusion (OR = 2.084), atelectasis (OR = 3.116), and extrapulmonary complications (OR = 4.251) were independent risk factors for RMPP (P < 0.05). MP antibody titer ≥1:320 (OR = 0.420) is a protective factor. The AUC of the prediction model was 0.870 (95%CI: 0.837, 0.904), the sensitivity of the prediction model was 82.2%, the specificity was 80.5%, and the prediction accuracy was relatively high. The calibration curve, close to the 45° line, exhibited good calibration.

We constructed and validated a visual and user-friendly model for individualized prediction of RMPP risk in children at initial presentation, to support clinical decision-making regarding macrolide therapy. This model provides a tool for identification of high-risk children, which may inform closer monitoring and prompt consideration of adjunctive therapies.

The outbreak and ongoing impact of coronavirus disease 2019 (COVID-19) have significantly affected people's physical and mental health, particularly among medical health workers. However, the effects of COVID-19 on the immunity of this population remain unclear.

This retrospective longitudinal study analyzed data from blood routine examinations of medical health workers conducted in 2019, 2020, 2022, and 2024. Data were collected from 1,818 participants, with subgroup analyses stratified by gender.

White blood cell (WBC), lymphocyte (LYM), and eosinophil (EOS) counts increased significantly in the post-COVID-19 year compared with the pre-COVID-19 year. Neutrophil (NEUT) counts decreased in COVID-19 year 1 and COVID-19 year 3 but returned to pre-COVID-19 year levels in the post-COVID-19 year. Monocyte (MONO) counts and monocyte-to-lymphocyte ratio (MLR) decreased in COVID-19 year 1, increased to pre-COVID-19 year levels in COVID-19 year 3, and reached their highest levels in the post-COVID-19 year. Basophil (BASO) counts and hemoglobin-to-red blood cell distribution width ratio (HRR) were significantly higher in COVID-19 year 1, COVID-19 year 3, and post-COVID-19 year than in pre-COVID-19 year. Platelet-to-lymphocyte ratio (PLR) in pre-COVID-19 year was significantly higher than in COVID-19 year 1 and post-COVID-19 year, but not significantly different from COVID-19 year 3. Neutrophil-to-lymphocyte ratio (NLR) significantly decreased in post-COVID-19 year when compared with pre-COVID-19 year. Aggregate index of systemic inflammation (AISI) in pre-COVID-19 year was significantly higher than in COVID-19 year 1 and COVID-19 year 3, but significantly lower than in post-COVID-19 year. Systemic inflammation response index (SIRI) decreased in COVID-19 year 1, but up to their pre-COVID-19 year levels in COVID-19 year 3 and post-COVID-19 year. Stratified analysis showed that the impacts of COVID-19 on immune cells and inflammation indicators were more pronounced in female.

Immune cells and inflammatory markers in medical health workers underwent changes between 2019 and 2024, particularly among female. Increased attention should be paid to the immune function and mental health of medical health workers.

Obstructive sleep apnea (OSA) is a significant risk factor for coronary heart disease (CHD), yet the precise pathophysiological mechanisms linking them remain incompletely understood. Remnant cholesterol (RC), as an atherogenic lipoprotein, is considered a key driver of residual cardiovascular risk. However, evidence regarding the role of RC in the association between OSA and CHD is still lacking.

In this single-center, cross-sectional study, we enrolled 368 consecutive patients with suspected coronary heart disease (CHD). All participants underwent overnight polysomnography (PSG) and were categorized into none/mild or moderate/severe obstructive sleep apnea (OSA) groups based on the apnea-hypopnea index (AHI). Coronary artery disease was assessed via angiography or computed tomography angiography (CTA), and its severity was quantified by the number of diseased vessels.

Compared to the none/mild OSA group, patients with moderate/severe OSA had a significantly higher prevalence of CHD (73.0% vs. 15.2%, p<0.001) and a greater proportion of multi-vessel disease (p<0.001). AHI was strongly positively correlated with the number of diseased vessels (overall population r=0.612, p<0.001). Multiple Linear Regression identified AHI as an independent determinant of the number of diseased vessels (β=0.804, p<0.001). Logistic regression confirmed that the number of diseased vessels was an independent risk factor for moderate/severe OSA (OR=3.575, p<0.001). While remnant cholesterol was not significantly correlated with AHI in the overall population (r=-0.051, p=0.327), it showed weak negative correlations with the number of diseased vessels in males (r=-0.120, p=0.036) and in the moderate/severe OSA subgroup (r=-0.130, p=0.035), which may be influenced by residual confounding factors.

This study demonstrates a strong and significant independent association between OSA severity and the presence and severity of CHD. Although remnant cholesterol showed no global association with OSA severity, its weak inverse correlation with coronary disease in males and severe OSA patients suggests a potential complex role, warranting further investigation into its mechanisms within specific populations.

To evaluate the prognostic value of disease distribution patterns and the baseline metabolic parameter, maximum standardized uptake value (SUVmax), on fluorine-18 fluorodeoxyglucose PET-computed tomography (¹⁸F-FDG PET-CT) in pediatric patients with Langerhans cell histiocytosis (LCH).

This retrospective study included 63 histopathologically confirmed LCH patients aged 1-18 years who underwent ¹⁸F-FDG PET-CT between August 2013 and 2025. Demographic, clinical, and imaging data were reviewed, including system involvement; risk and critical organ involvement; treatment regimens; survival time; and outcomes. Baseline SUVmax and disease distribution patterns were correlated with event-free survival (EFS) and overall survival (OS).

Of 63 patients, 40 (63.5%) were male and 23 (36.5%) females. Single-system involvement was observed in 32 (51%) patients, while 31 (49%) had multisystem disease. Risk-organ involvement (RO+) occurred in 12 (38.7%) multisystem patients, and critical organ involvement in 10 (32.2%). Diabetes insipidus was present in nine (14%) patients. Mean SUVmax was significantly higher in deceased patients than survivors (6.7 ± 1.8 vs. 4.7 ± 3.0; P = 0.01). Ten-year EFS was significantly better in single-system LCH than multisystem LCH (90.6 vs. 64.5%; P = 0.03) and worse in RO+ multisystem LCH than without risk-organ-involvement multisystem LCH (50 vs. 73.7%). Ten-year OS was higher in single-system LCH than multisystem LCH (93.8 vs. 74.2%; P = 0.04) and lower in RO+ multisystem LCH (50 vs. 89.5%; P = 0.01).

Single-system LCH demonstrates significantly better survival outcomes than multisystem LCH, particularly without risk-organ involvement. Baseline SUVmax appears to be a promising prognostic imaging biomarker for predicting outcomes in pediatric LCH.

BackgroundThe combined use of extracorporeal cardio-pulmonary resuscitation (ECPR) and large bore mechanical thrombectomy represents an emerging strategy for patients experiencing cardiac arrest secondary to catastrophic pulmonary embolism.MethodsThis retrospective, single-center study included patients treated between January 2023 and June 2025 who experienced cardiac arrest due to catastrophic pulmonary embolism and underwent ECPR followed by large bore mechanical thrombectomy. Primary outcomes were 90-days post-discharge survival and cerebral performance category (CPC) at discharge. Secondary outcomes included support duration, complications during support, and ICU and hospital length of stay.ResultsFifteen patients were included. Four (27%) sustained out-of-hospital cardiac arrest, and twelve (80%) presented with pulseless electrical activity. All patients underwent large bore mechanical thrombectomy using the Inari FlowTriever System (Inari Medical, Irvine, CA) within 6 hours of arrest in the cardiac catheterization laboratory. Eight patients (53%) survived to discharge with favorable neurological outcomes (CPC 1-2). Seven patients died following withdrawal of care due to cerebrovascular accident or anoxic brain injury (n = 4), intracranial hemorrhage (n = 2), or mesenteric ischemia (n = 1). Cerebrovascular or anoxic brain injury occurred more frequently among non-survivors (p = 0.02). No significant differences were observed in baseline characteristics, ECMO or ventilator duration, or length of stay between survivors and non-survivors.ConclusionECPR followed by large bore mechanical thrombectomy is a feasible resuscitative strategy for patients presenting with catastrophic pulmonary embolism. Larger, multicenter studies are warranted to better define outcomes and the overall impact of this combined approach.

 : Cystic fibrosis (CF) is likely underdiagnosed in Caribbean populations due to non-representative cystic fibrosis transmembrane conductance regulator (CFTR) variant screening panels, limited newborn screening programs, and structural healthcare barriers. Data from 2022 indicate substantial populations with European ancestry in Puerto Rico (1.4 M, 42.7%) and the Dominican Republic (1.4 M, 57.9%), yet the true burden of CF in the broader Caribbean remains largely undocumented.

Current diagnostic frameworks, largely based on European-derived CFTR variant distributions, fail to capture the true burden of CF in Caribbean populations, leading to underestimated prevalence and delayed or missed diagnoses.

To synthesize registry, clinical, and published data to identify barriers to accurately assessing CF prevalence in Caribbean populations.

This narrative literature review integrates CF registries, published data on CFTR variant distribution, population ancestry data, and clinical observations from CF centers in Puerto Rico and the Dominican Republic. Clinical insights were derived from pediatric patients evaluated at the Pediatric Rare Lung and Asthma Institute in Puerto Rico and the CF Clinic at Robert Reid Cabral Children's Hospital in the Dominican Republic.

CFTR variant patterns differ from those in the United States, with higher frequencies of rare variants such as p.Ala559Thr. Standard screening panels may miss these variants, contributing to underdiagnosis. Limited newborn screening, misdiagnosis, and restricted access to CFTR modulator therapies further exacerbate disparities.

Structural, diagnostic, and genetic factors hinder accurate CF prevalence estimates in the Caribbean, highlighting the need for region-specific research, improved screening, and expanded access to therapies.

Bronchiolitis represents a major cause of infant hospitalization, predominantly due to respiratory syncytial virus (RSV). Nirsevimab, a long-acting monoclonal antibody targeting the prefusion RSV F protein, has recently been introduced to provide season-long protection against RSV-related lower respiratory tract infection.

We conducted a multicenter, retrospective, population-based study across the Liguria Region (Northwest Italy) to assess the impact and effectiveness of the 2024-2025 nirsevimab immunization campaign. All infants under 2 years of age hospitalized with acute bronchiolitis between October 2023 and March 2025 were identified through the regional pediatric Hub-and-Spoke network. Data were compared between the pre-nirsevimab (2023-2024) and post-nirsevimab (2024-2025) seasons. Nirsevimab effectiveness (VE) against RSV-positive hospitalization was estimated using a test-negative design.

A total of 858 infants were hospitalized with bronchiolitis across the two seasons. Following the introduction of nirsevimab, bronchiolitis hospitalizations decreased from 41.7 to 17.3 per 1000 admissions (Incidence Rate Ratio 0.4; 95% CI: 0.4-0.5; p < 0.001), corresponding to a 60% reduction. Estimated nirsevimab effectiveness was 65.0% (95% CI: 39.2%-79.8%) against RSV-positive hospitalization. No high-risk infants-those previously eligible for palivizumab-developed severe RSV infection requiring PICU admission. Breakthrough infections occurred in a minority of immunized infants but showed a similar clinical course to non-immunized cases.

The introduction of universal nirsevimab immunization in Liguria was associated with a marked reduction in RSV-related hospitalizations, confirming its strong real-world epidemiological impact. These findings support nirsevimab as an effective and feasible public health intervention to substantially reduce the burden of RSV bronchiolitis in infants.

Achieving long-term behavioural change in chronic disease management, particularly in chronic obstructive pulmonary disease (COPD), remains a significant challenge. Although maintenance programmes have been developed to extend the benefits of pulmonary rehabilitation, patient adherence is often comperomised by persistent symptoms, low motivation, and fragmented care. Research highlights the importance of therapeutic alliance, social support, and personalised follow-up to encourage long-term healthy behaviour. Care managers (CMs) may help facilitate these key elements by providing individualised support and coordination. The aim of this study is to identify key elements that support the sustainable implementation of the CM role in chronic care pathways, by exploring the shared experiences of COPD patients and CM involved in an 18-month remote follow-up post-rehabilitation programme.

A qualitative descriptive study was conducted using semi-structured interviews with COPD patients and care managers who participated in the INSPIR'ACTION national experiment. This programme included an initial pulmonary rehabilitation phase followed by an 18-month remote follow-up. Interviews focused on the follow-up phase and were analysed using inductive thematic analysis.

Data saturation was reached with a final sample of 9 patients and 7 CMs. Patients described CMs as supportive professionals who helped sustain motivation, adherence to healthy behaviours, and continuity of care. The relationship was perceived as trustful and personalised, even in a remote format. CMs expressed pride in their role but also reported organisational challenges, including lack of recognition and insufficient time allocation. Both groups emphasised the importance of relational continuity and individualised support.

Patients and care managers described the CM as a key supportive figure offering personalised follow-up perceived as helping promote therapeutic engagement and behavioural change. Relational continuity throughout the remote follow-up was seen as fostering a trusting relationship that shaped participants' experience of the programme. By highlighting organisational elements that could influence implementation, our study may help inform future strategies to enhance the sustainable integration of care management in COPD care pathway.

COPD patients and CMs involved in the INSPIR'ACTION programme shared their experiences through interviews, helping to identify key factors for improving care manager support and long-term follow-up. Their input directly informed the study's findings and recommendations.

While COVID-19 had a devastating impact on mental health worldwide, little is known about its effects on adults with intellectual and developmental disabilities. We used a community-based participatory approach to study this population's mental health experiences.

Six focus groups were conducted: four with adults with intellectual and developmental disabilities (n = 21) and two with caregivers (n = 13). Conventional content analysis and thematic network analysis were utilised.

We identified cascading impacts of the pandemic on the mental health of this population. Sub-themes included: (1) environmental effects, (2) emotional effects and (3) physical and behavioural effects of COVID-19. Five modifying factors were identified.

The COVID-19 pandemic, while specific in its restrictions and timing, illustrated and exacerbated unmet mental health needs of adults with intellectual and developmental disabilities. These results suggest opportunities for empirical research and policy development, relevant for future emergencies and ongoing medical and non-medical support of this population.