The role of inhaled colistin as either an adjunctive or substitution for nosocomial pneumonia (NP) caused by carbapenem-resistant organisms (CRO) is highly debated due to conflicting clinical evidence. Given the limitations of intravenous therapy, the optimal administration strategy remains a critical, unresolved question. This study aimed to compare the efficacy and safety of three colistin-based regimens administered via different routes.

In this prospective cohort study, 127 intensive care unit (ICU) patients diagnosed with CRO-related NP and treated with colistin were enrolled. Patients were classified into three groups according to the route of administration: inhalation (IH group), intravenous colistin with adjunctive inhalation (IV+IH group), and intravenous (IV group) therapy. The primary endpoint was clinical efficacy at the end of treatment. Key secondary outcomes included microbiological eradication and nephrotoxicity.

Clinical efficacy was achieved in 72.1% of the IH group, 67.4% of the IV+IH group, and 65% of the IV group, with no statistically significant difference among groups (P=0.786). The IH group demonstrated a significantly higher microbiological eradication rate compared with the IV group (P=0.004). No significant differences were observed in 28-day all-cause mortality, hospital stay duration, or incidence of acute kidney injury (AKI). Moreover, the development of AKI during treatment was strongly associated with clinical failure, suggesting it may serve as a prognostic marker for poor outcomes.

In critically ill patients with CRO-associated NP, inhaled colistin monotherapy provided comparable clinical efficacy to systemic administration. It achieved superior microbiological eradication and showed a favorable safety profile regarding nephrotoxicity, suggesting it represents a viable and potentially safer therapeutic strategy.

Rates of central precocious puberty (CPP) are increasing worldwide; however, contemporary population-based studies remain limited in many settings, including Türkiye, and temporal patterns across the COVID-19 period are incompletely characterised. To address these gaps we aimed to quantify national incidence and prevalence of treated CPP from 2018 to 2024 and to describe temporal patterns across the COVID-19 period and geographic variation.

We conducted a retrospective, population-based registry study using Türkiye's national electronic health record system (e-Nabız). For incidence analyses, we included girls aged <10 years and boys aged <11 years between Jan.1,2018, and Dec.31,2024; prevalence analyses included girls aged ≤11 years and boys aged ≤12 years to capture ongoing treatment. CPP cases were identified using a combined diagnostic and treatment algorithm requiring pediatric endocrinology evaluation, CPP-related ICD-10 coding at point of care, and sustained GnRHa treatment (≥3 prescriptions issued on separate dates, with a minimum interval of 15 days). Annual incidence and prevalence were calculated using Turkish Statistical Institute denominators and stratified by sex, year, and region.

We identified 41-169 treated CPP cases, 95.6% in girls (39380/41169). National incidence increased from 25 to 54 per 100,000 between 2018 and 2024, and prevalence from 23 to 112 per 100 000. Annual case counts peaked following the COVID-19 period (3816 in 2019 to 7653 in 2021) and subsequently plateaued above pre-pandemic levels.

In this national, population-based study from Türkiye, the incidence of treatment-initiated CPP increased substantially between 2018 and 2024, with a pronounced rise during the COVID-19 period and persistently higher levels thereafter. These findings are relevant for pediatric endocrine service planning and population-level public health strategies, but should be interpreted as temporal trends in specialist-confirmed, treatment-requiring CPP rather than the full clinical spectrum of CPP (including the pandemic period) or a direct measure of biological pubertal onset in the general population.

Since the emergence of SARS-CoV-2 in 2019, Long COVID has emerged as a significant global public health challenge. The identification of accessible biomarkers and risk factors is critical to enabling early intervention and improving long-term outcomes.

This prospective cohort study enrolled 2,792 individuals with confirmed COVID-19 from Anhui Province in September 2024. A propensity score matching analysis was performed using a 1:4 ratio. Cases and matched controls were selected from cohort, serum sample were analyzed to assess hematological parameters. Multivariable logistic regression models were applied to identify independent risk factors associated with the development of Long COVID.

2,792 participants (average age 51.64 years) identified 182 (6.52%) long COVID patients during follow-up. Common symptoms included fatigue, cough, insomnia, throat discomfort, and appetite loss. After propensity score matching, risk factors were age, more severe acute symptoms. Long COVID patients exhibited higher red blood cell counts but lower hemoglobin-related indices and platelet count.

This study confirms the persistent risk of Long COVID following reinfection, with heightened susceptibility associated with advanced age, specific acute-phase symptoms. Alterations in routine hematological parameters may serve as valuable biomarkers for the monitoring and management of Long COVID.

Overuse of antibiotics among patients with upper respiratory tract infections (URTIs) is a worldwide problem. In China, approximately 70% of outpatients with URTIs are treated with antibiotics, often via intravenous infusion. This study aimed to evaluate whether a pharmacist-led multidimensional intervention reduces the use of intravenous (IV) antibacterial drug infusion among patients with bacterial URTIs.

This study employed a pragmatic, parallel controlled, cluster-randomized superiority trial design. Outcome assessment and data analysis were conducted in a blinded manner, while treatment administration remained unblinded. A total of 28 hospitals in Zhejiang Province, China, were randomly allocated in a 1:1 ratio. In the intervention arm, a multidimensional intervention embedded in routine emergency treatment will be applied, involving both doctors and patients. The interventions included systematic physician training, clinical decision support cards, and printed educational materials for patients. Patients admitted to the sites assigned to the control arm will receive usual care at the discretion of treating physicians. The primary outcome was the rate of intravenous antibacterial drug infusion during the index admission. Secondary outcomes included the duration of URTI symptoms, adverse events, proportion of eligible patients who received subsequent antibiotics, frequency of re-consultation, and hospitalization within the follow-up period. The final follow-up was completed by 14 days post-discharge. Participants will be included from August 1, 2025, to January 31, 2026.

This study will demonstrate the feasibility and potential impact of a pharmacist-led, multidimensional intervention aimed at reducing IV antimicrobial use in patients with bacterial URTIs.

ClinicalTrials.gov, identifier NCT06620341.

Elderly patients are particularly vulnerable to pulmonary infections due to immune system decline and comorbidities. This study aims to evaluate the distribution of bacterial pathogens, patterns of antimicrobial resistance, medication strategies, and risk factors associated with mortality in elderly patients with pulmonary infections.

Data were collected from electronic medical records, encompassing demographic information, clinical characteristics, laboratory results, treatment strategies, and outcomes. Risk factors associated with mortality were identified using the Least Absolute Shrinkage and Selection Operator regression model and were subsequently validated through multivariable logistic regression. Differences between groups were assessed using the independent t-test or Mann-Whitney U-test for continuous variables, and the chi-square test or Fisher's exact test for categorical variables.

201 patients were included with 70.6% being male. Clinical improvement was observed in 124 patients, while 77 patients died. Gram-negative bacteria were identified as the most common pathogens, with Acinetobacter baumannii (27.5%), Klebsiella pneumoniae (23.5%), and Pseudomonas aeruginosa (13.2%) being the most frequently isolated species. Notably, 66.0% of the bacterial strains were classified as multidrug-resistant. Furthermore, 65.7% of the patients received combination therapy. Seven risk factors associated with mortality were identified. Body mass index emerged as a protective factor, whereas length of duration, gastrointestinal bleeding, respiratory failure, bacteremia, myocardial infarction, and mechanical ventilation significantly increased the risk of death.

Respiratory failure, mechanical ventilation, gastrointestinal bleeding, extended hospitalization, bacteremia, myocardial infarction, and malnutrition were key risk factors related to mortality in elderly patients with pulmonary infections. Early identification and intervention targeting these risk factors are crucial for improving clinical outcomes.

As natural disasters become more frequent and severe, examining their impact on health care access is increasingly important. This study was a community-level assessment of the effects of flooding and COVID-19 on access to health care services.

This study utilized a self-administered survey in flood-prone Houston communities. Bivariable associations of having experienced flooding damage, as well as having a history of COVID-19 diagnoses, were examined by demographics and health care access using chi-square analyses, t-tests, and both unadjusted and adjusted logistic and Poisson regression models.

Among 206 surveys, 20.39% reported homes or vehicles lost to flooding, and 33.5% had been diagnosed with COVID-19. Those who experienced flooding were 3 times more likely to report their closest hospital closed, their doctor's office closed, delays filling prescriptions, not getting needed medical care, and delayed medical care access. Experiencing both COVID-19 and flooding was even more strongly associated with the frequency of health care services lost.

These findings highlight the need for expanded health care access and support services that accommodate localized damages in communities susceptible to adverse events. Future planning for disasters should include plans for expanded access to health care resources for those with comorbidities and low-socioeconomic groups.

Pediatric invasive Group A Streptococcus (iGAS) infections are rare, affecting sterile sites including the central nervous system (CNS), and cause significant morbidity and mortality. An increased incidence of pediatric iGAS infections, including cases with CNS involvement, has been noted following the COVID-19 pandemic both domestically and internationally. Regional New England iGAS data specific to pediatric populations have been limited. This case series describes three pediatric cases of iGAS with CNS involvement which presented within the same two-month period in early 2025, all from within 20 miles in Massachusetts. All were initially admitted to the pediatric intensive care unit, patients had meningitis and subdural collections on brain imaging, and subsequently required at least four weeks of intravenous antibiotics. One underwent surgical intervention. All three had seizures requiring long-term anti-epileptic therapy, and each had residual symptoms, including seizures, focal weakness, and developmental delay. GAS infections with intracranial involvement are often severe and life-threatening. This series of three pediatric intracranial iGAS cases is particularly unique due to their similar presentations, timing, and geographic proximity. With recent literature indicating rising rates of iGAS infections globally and our regional experience, GAS should be considered a potential culprit for patients presenting with invasive bacterial infections.

Respiratory syncytial virus (RSV) is a major cause of morbidity and mortality among older adults. Limited information is available in Israel regarding RSV outcomes, particularly compared to influenza, to guide strategies for RSV vaccination. This study aimed to characterize RSV infection and predictors of clinical outcomes among hospitalized adults aged ≥ 60 years in Israel between 2016 and 2023, and to compare disease severity and outcomes with those of seasonal influenza hospitalizations.

A retrospective analysis was conducted of hospitalized adults aged ≥ 60 years with positive RSV or influenza confirmed via standard-of-care RT-PCR between 2016 and 2023. The primary outcome was a composite of intensive care unit (ICU) admission, mechanical ventilation, vasopressor support, or 30-day mortality. Cardiovascular complications were recorded. An inverse probability treatment weighting (IPTW) was used to adjust for potential confounding. Weighted and unweighted relative risks (RRs) were estimated to compare clinical outcomes between RSV and influenza.

Overall, 817 RSV-positive and 2113 influenza-positive patients were included. Among patients with RSV, 30-day and 90-day mortality rates were 11.9% and 18.8% respectively; ICU admission was required for 10.6%, mechanical ventilation for 6.4%, and vasopressor support for 6.5%. Tachyarrhythmia was documented in 17.7% and ischemia in 9.9%. Predictors of the composite primary outcome included chronic pulmonary disease, lower respiratory tract infection, hypothermia, elevated pulse, lower blood pressure and increased creatinine. In IPTW-adjusted analyses, RSV infection had a trend for increased risk for the composite primary outcome (RR 1.03, 95% confidence interval [CI] 1.00, 1.06) and 90-day mortality (RR 1.02, 95% CI 0.99, 1.05) compared with influenza.

Among hospitalized older adults, RSV infection carries considerable morbidity and mortality and may have a higher risk for poor clinical outcomes compared with influenza. These findings support the prioritization of RSV vaccination programs among older adults.

Current one-pot clustered regularly interspaced short palindromic repeats diagnostics are limited by the cis-cleavage activity of Cas nucleases, which leads to amplicon degradation during amplification. Here, we report a streamlined strategy that overcomes this limitation. By integrating a bipartite split-crRNA into Cas12a (SCas12a), we separate target recognition from PAM dependency and completely eliminate cis-cleavage while preserving robust trans-cleavage. This strategy is broadly applicable for one-pot testing, compatible with recombinase polymerase amplification, RT-RPA, and loop-mediated isothermal amplification, as well as multiple Cas12a orthologs, including As, Lb, and Ct Cas12a. Moreover, the SCas12a accelerates one-pot testing with 100-1000-fold improved sensitivity and achieves >10-fold reduction in time-to-signal, enabling detection of targets at attomolar levels within 30 min. Additionally, it provides single-base resolution with up to 91-fold selectivity. The system has been successfully applied to detect HPV16, SARS-CoV-2, and TP53 SNPs in clinical samples. Together, we have developed a PAM-independent and cis-cleavage-free one-pot Cas12a assay, which holds strong potential for point-of-care diagnostics.

Pulmonary arterial hypertension (PAH) is a severe, progressive disease characterized by elevated pulmonary arterial pressure and increased vascular resistance. This hemodynamic strain forces the right ventricle to pump against a high-pressure system, ultimately leading to right-sided heart failure and death. The pathogenesis of PAH involves a complex interplay of vasoconstriction, chronic inflammation, and pathological remodeling of the pulmonary vessel walls-specifically hypertrophy of the smooth muscle and intimal layers-driven by molecular imbalances and genetic predispositions. Current FDA-approved therapies primarily manage symptoms through vasodilation but fail to directly target the underlying vascular remodeling. Imatinib, a tyrosine kinase inhibitor originally developed for oncological indications, has emerged as a potential disease-modifying agent for PAH. By inhibiting platelet-derived growth factor receptors (PDGFR), imatinib targets the aberrant proliferation of smooth muscle cells, offering a mechanism to potentially reverse or arrest vascular remodeling. Clinical trials, including the IMPRES study, have demonstrated encouraging hemodynamic improvements in patients with severe PAH refractory to standard therapies. However, systemic safety concerns and dose-dependent adverse reactions have limited its clinical approval. This review examines the pharmacological rationale for imatinib, its impact on vascular structure, and the safety signals observed in long-term studies. Furthermore, it discusses emerging strategies, such as inhaled formulations and pharmacogenetic approaches (e.g., the PIPAH study), aimed at enhancing the efficacy-to-safety ratio of kinase inhibitors to improve long-term outcomes for patients with PAH.