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Chemical esophageal burns in children, especially grade III injuries, frequently lead to cicatricial strictures, persistent dysphagia, and prolonged hospitalization, creating a high risk of complications and disability. Traditional dilation methods (blind bougienage and gastrostomy with string-guided bougienage) remain widely used; however, they are associated with limited effectiveness and a risk of perforation. This study aimed to evaluate real-world outcomes of these traditional approaches and to define their main clinical limitations. A retrospective analysis was performed in 115 children (aged 1-14 years) with chemical esophageal burns treated in a hospital setting. Grade III esophageal burns with subsequent cicatricial stricture formation were diagnosed in 46 patients. The severity of stenosis was assessed using the Yu.I. Gallinger classification. Treatment selection was determined by the severity of deformity: direct bougienage was performed when luminal passage was possible, while gastrostomy with string-guided bougienage was used in cases of severe stenosis, inability to safely pass a bougie, or after ineffective blind bougienage. Final clinical outcomes were assessed during hospitalization (at discharge). Because treatment selection depended on stenosis severity and technical feasibility, between-method comparisons were interpreted descriptively in view of confounding by indication. All patients with grade III burns had cicatricial stenoses of grades II-IV: grade II - 45.6%, grade III - 43.5%, and grade IV - 10.9%. Direct bougienage was feasible as the primary method in 45.7% of cases, whereas gastrostomy with string-guided bougienage was used in 54.3%; this distribution should be interpreted with caution because gastrostomy was preferentially selected for more severe deformity or after failed blind bougienage. Esophageal perforation was recorded in 6.9% of patients. In alkali burns, a 1.6-fold higher need for gastrostomy was observed than in acid burns (73.3% vs 45.2%), but the difference did not reach statistical significance (p=0.115). The mean length of hospital stay was 41.1±2.9 bed-days. Final in-hospital clinical outcomes were: good - 67.4%, satisfactory - 19.6%, and unsatisfactory - 13.0%. Traditional treatment methods for grade III chemical esophageal burns in children demonstrate important clinical limitations, including a risk of perforation and a frequent need for gastrostomy in severe cases. Given the retrospective design, selection by indication, and the absence of a direct comparison with visually controlled techniques, further comparative studies are needed to determine whether safer dilation under visual or guidewire control improves outcomes.

Pediatric sepsis is a leading cause of global morbidity and mortality, yet high-resolution, granular subnational assessments remain scarce. Chile and Mexico are the only countries in Latin America that possess robust vital registration systems and open access databases with marginal levels of missing cases. This offers a unique opportunity to quantify the subnational burden of pediatric sepsis, identify healthcare system constrictions, and guide targeted public health interventions. This retrospective longitudinal study analyzed official hospital discharge and non-fetal death records of pediatrics (<&#x2009;10 years old) from Chile and Mexico between 2014 and 2024. Age-standardized incidence (ASIR) and mortality (ASMR) rates, standardized ratios, and the mortality-to-incidence ratio (MIR), were calculated to assess mortality relative to subnational hospital output. A novel dynamic risk stratification matrix was developed to classify ICD-10 sepsis-related causes into four risk/severity quadrants based on year-specific ASIR and MIR indicators. A total of 656,234 discharges and 2,035 deaths in Chile, and 964,452 discharges and 77,252 deaths in Mexico were analyzed. Subnational trends were highly heterogeneous. Chile exhibited a predominantly low pediatric MIR (median&#x2009;<&#x2009;1%) with isolated hotspots with significant structural deviations to the North. High-severity sepsis causes in Chile were relatively rare. Conversely, Mexico displayed an alarmingly high MIR (median 7.2%), with systemic persistency in States such as Chiapas and Nuevo Le&#xf3;n. Strikingly, high-severity causes in Mexico (e.g., unspecified septicaemia, bacterial meningitis) were highly frequent, accounting for 88-97% of pediatric sepsis deaths. Furthermore, systemic instances of code-specific MIR&#x2009;>&#x2009;1.0 in Mexico suggest significant health system fragmentation and decoupling of hospital discharge from vital statistic registries. Pediatric sepsis in Latin America encompasses distinct realities, ranging from localized critical care gaps to high-lethality persistency. One-size-fits-all national policies may be inadequate. These findings advocate for precision public health, urging the deployment of decentralized, data-driven interventions and specialized resource allocation based on high-risk subnational hotspot identification.

Previously, young children had limited respiratory support options during interfacility transport. Recently, high-flow nasal cannula (HFNC) and noninvasive ventilation (NIV) have become available for pediatric transport. We hypothesized that the implementation of HFNC and NIV on interfacility transport decreases the rate of intubation in infants and toddlers before and after transport to a tertiary-care pediatric intensive care unit (PICU). We conducted a retrospective chart review of children aged 30 days to < 36 months transported to a tertiary-care PICU from a referring hospital with respiratory distress from 2014 to 2019. Groups were analyzed before (2014-2017) and after the implementation (2017-2019) of HFNC and NIV during transport. NIV was defined as positive pressure ventilation delivered through nasal cannula. The primary outcome was to compare the pre- and postimplementation groups with regard to the rate of intubation before transport and within 48 hours of PICU admission. Secondary outcomes were the association between intubation rate and comorbidities and the comparison of length of respiratory support and hospital length of stay between the pre- and postimplementation groups. A total of 262 patients met criteria, 133 before and 129 after the intervention. The rate of intubation before PICU admission was 44% in the preintervention group versus 36% in patients transported after the implementation of HFNC and NIV, a trend that was not statistically significant (P = .19). The rate of intubation within 48 hours of PICU admission was 8% (before) and 11% (after) with no statistical significance (P = .48). Comorbidities were not associated with an increased rate of intubation before transport (P = .09) or within 48 hours of admission (P = .45). Hospital length of stay and length of respiratory support were not different between pre- and postintervention groups (P = .18 and P = .3, respectively). The availability of HFNC/NIV was associated with a significant decrease in the proportion of patients who received oxygen via nasal cannula or face mask during transport (46% before vs. 13% after the intervention; P < .01). After the introduction of HFNC/NIV during transport to a large tertiary-care hospital in a major metropolitan area, fewer nasal cannula/face masks were used during transport in favor of HFNC/NIV but no significant change in intubation rates was found.

This study aimed to evaluate the effectiveness of the China Acute Seizure Action Plan (CASAP), a context-adapted acute seizure action plan developed for China, on caregivers' knowledge, attitudes, and practices (KAP) regarding out-of-hospital seizure management for children and adolescents with epilepsy (0-18 years). A prospective before-and-after study was conducted with 313 caregivers of pediatric patients with epilepsy at Chongqing Medical University Affiliated Children's Hospital from August 2023 to October 2024. Participants received a 6-month CASAP intervention. Caregivers' KAP levels were assessed before and after the intervention using a self-designed questionnaire, and paired statistical tests and subgroup analyses were applied to compare pre- and post-intervention outcomes. Knowledge and practice scores improved significantly (p < 0.001), whereas attitude scores showed no significant change (p > 0.05). Caregivers using the seizure-management app showed better knowledge and practice scores (p < 0.05). KAP scores varied significantly according to caregivers' education level (p < 0.001), but no significant differences were found based on the duration of the child's illness (p > 0.05). The CASAP improved caregivers' epilepsy-related knowledge and emergency response practices. Digital tools may further enhance intervention outcomes, whereas attitude changes require long-term follow-up and psychological support. These findings support the promotion of context-adapted epilepsy management strategies outside of hospitals.

Adiposity trends in pediatrics are increasing, escalating the risk for chronic diseases, psychological disorders, and adulthood obesity; creating more complex patients at younger ages. Organizations struggle with excess body weight (EBW) screening and follow-up compliance due to a misunderstanding of the problem, provider bias, discomfort discussing weight-related topics, and improper data collection and recording. An evidence-based quality improvement (EBQI) initiative, following the Johns Hopkins Nursing Evidence-Based Practice model and Plan-Do-Study-Act, was undertaken in a private, for-profit, pediatric primary care organization, measuring screening and quarterly follow-up scheduling rates. Processes and structures for conducting EBW screening and follow-up appointments were reviewed and amended based on the literature. A university hospital endocrinology department educated participants on the impact of EBW in pediatric patients, proper screening, diagnosis, and follow-up. Implementation of this EBQI initiative resulted in average increases of 56% for body mass index (BMI) screenings and 1,100% in BMI follow-up visits scheduled compared to baseline data. EBQI initiatives that promote BMI screening and follow-up compliance positively impact organizational outcomes and ultimately patient outcomes.

The study aimed to investigate the prevalence of osteoporosis in children and adolescents with transfusion-dependent thalassemia (TDT) and evaluate the diagnostic value of different osteoporosis indicators. Clinical data were collected from children and adolescents with TDT treated with blood transfusion between March 2022 and January 2024 at Huizhou Central People's Hospital and Huizhou First Hospital. The patients were grouped according to the presence of osteoporosis (International Society for Clinical Densitometry [ISCD] criteria). Of 138 patients included in the study, 48 (34.8%) had osteoporosis. The patients with osteoporosis mainly had asymptomatic grade I fractures of the spine. Using the dual-X-ray absorptiometry (DXA) standards from the World Health Organization, height-corrected TBLH Z-score &#x2264;-2 was associated with osteoporosis (30.4% vs. 14.9%, P&#x2009;=&#x2009;0.035), displaying 30.4% sensitivity and 85.1% specificity. According to the Chinese DXA standards, height-corrected and age-specific Z-scores &#x2264;-2 were not associated with osteoporosis. The prevalence of osteoporosis among children and adolescents with TDT was 34.8%, indicating the need for screening for osteoporosis in that population. In TDT, the diagnosis of osteoporosis requires early detection of spinal fractures because bone density assessed by DXA is of limited value.

This study reviewed pediatric cases managed by the Aeromedical Evacuation Squadron (AMES) of the Japan Air Self-Defense Force and analyzed patient characteristics. Pediatric transportation cases (n = 34) between 2006 and 2023 were reviewed. Data on patient age, main disease, transportation purpose and distance, and use of mechanical ventilators or extracorporeal membrane oxygenation (ECMO) were obtained by referring to the records. The average (standard deviation) patient age was 5.7 (5.8) years (range: 0-16 years), and 17 patients (50%) were younger than 1 year of age. Furthermore, 10 (58.8%) of these 17 children were younger than 7 months of age and 1 child was under 1 month of age. The most common diseases in the overall patient population were cardiovascular diseases (CVDs, n = 18) and respiratory diseases (RDs, n = 14). The purposes of transportation in cases of 17 patients with CVDs and 3 patients with RDs were the implantation of a ventricular assist device and lung transplantation, respectively. The average transportation distance was 453.7 (218.6) (range: 176.9-962.8) miles or 730.2 (351.8) (range: 284.7-1,549.5) km, and in 8 cases, the transportation distance was > 600 miles. Of the patients, 29 (85.3%) were fitted with a ventilator, of whom 8 received ECMO (6 with CVDs and 2 with RDs). In all cases, physicians from the transporting hospitals were on board. There were no cases of cardiac arrest during the transportation. AMES plays an important role, especially in the long-distance transportation of critically ill children.

Post-obstructive pulmonary edema (POPE) is a rare, life-threatening complication of strangulation. Management is based on low-grade evidence, and outcomes are poorly characterized. To report a systematic review of POPE following near-hanging, illustrated by a case report that represents the first documented African case. We combined a novel case report with a systematic review of published case reports and case series, conducted per a pre-registered protocol on the Open Science Framework (OSF). A clinical trial number was not applicable. A comprehensive search of major databases identified all relevant published cases. Data on demographics, management, and outcomes were extracted and synthesized descriptively. Fifteen cases from 11 publications were included. Patients were predominantly young (median age 24). Symptoms overwhelmingly presented pre-hospital (93%). Glasgow Coma Scale (GCS) on admission was low (median 6), and the overall mortality rate was 40% (6/15). Adjunctive therapies were reported to be administered more frequently in survivors than in non-survivors, including diuretics (55.6% vs. 16.7%) and corticosteroids (44.4% vs. 16.7%), representing a potential clinical signal. POPE following strangulation is associated with high mortality in young, otherwise healthy populations. This review identified a tentative association between adjunctive diuretic or corticosteroid therapy and improved survival. While these hypothesis-generating findings require cautious interpretation due to the low-level evidence, they represent a potential clinical signal necessitating further prospective evaluation and standardized reporting.

Tympanoplasty repairs tympanic membrane (TM) perforations using grafts. In pediatric patients, cartilage grafts are preferred over fascia due to superior mechanical properties that prevent complications from negative middle ear pressure, including graft failure, retraction, and cholesteatoma formation. However, autologous grafts cause donor-site morbidity and increased surgical time. To overcome these limitations, we engineered an allogeneic porcine meniscus decellularized (MEND) fibrocartilage graft with a unique microchannel structure created by selective elastin and vascular digestion to promote host cell invasion and integration. We evaluated MEND in a rat TM acute perforation model, comparing outcomes to autologous cartilage and fascia grafts, the current clinical standards of care. TMs were monitored via otoendoscopy through 4 weeks, then analyzed by histology and immunohistochemistry. MEND and auricular cartilage grafts successfully closed perforations by day 3, outperforming fascia grafts which frequently dislodged due to poor mechanical integrity. However, unlike cartilage grafts, MEND fully remodeled by day 28, providing superior graft closure and tissue integration compared to both traditional materials. These findings demonstrate MEND's potential as an off-the-shelf solution for pediatric tympanoplasty.

Long-acting injectable buprenorphine may be a promising treatment option for adolescents and young adults with opioid use disorder (OUD). However, little is known about its safety, tolerability, and effectiveness in this age group. We conducted a 1-year feasibility study of elective inpatient buprenorphine induction followed by administration of long-acting injectable buprenorphine and linkage to ongoing substance use care in individuals <21&#x202f;years in a safety-net health system (n&#x202f;=&#x202f;18). Eighteen of 22 (82%) of patients admitted to an inpatient unit for buprenorphine initiation opted to receive the long-acting injectable formulation upon completion of induction. Of 18 patients who received long-acting injectable buprenorphine, 15 (83%) and 12 (67%) remained in care at one- and two-months post discharge, respectively. Eleven (61%) participants received repeat doses at both one- and two-months post discharge. Fourteen (78%) and 12 (67%) participants had not returned to opioid use at one- and two- months post discharge, respectively. The findings from this study of adolescents and young adults with OUD demonstrated that inpatient initiation of long-acting injectable buprenorphine after a brief induction with short-acting buprenorphine may be safe, well tolerated, and effective in terms of linkage, retention in care, and return to opioid use.

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Connexin 43 (Cx43) exhibits remarkable functional diversity that is precisely dictated by its dynamic subcellular localization. Beyond its canonical role at the plasma membrane, where it assembles into gap junctions (GJs) and hemichannels (HCs) to mediate intercellular communication, Cx43 translocates to the nucleus and mitochondria, where it exerts non-channel functions including transcriptional regulation and metabolic adaptation. At the plasma membrane, dysregulation of Cx43 trafficking, anchoring, or turnover leads to excessive HC opening and impaired GJ communication, contributing to cardiovascular arrhythmias, ischemia-reperfusion injury, neuroinflammation, osteoporosis, and retinopathy. In the nucleus, Cx43 or its C-terminal fragment enters through importin-dependent pathways, functioning as a non-canonical transcriptional regulator; its mislocalization is implicated in cancer (context-dependent suppression or promotion), hepatic gluconeogenesis in diabetes, and tissue fibrosis. Within mitochondria, Cx43 is imported via Hsp90/TOM complex- or GJA1-20&#x202f;k-dependent pathways, where it regulates K+ transport, respiratory chain activity, and redox balance; this mitochondrial pool exerts cardioprotection under preconditioning but exacerbates diabetic cardiomyopathy and neurological injury under pathological stress. This review synthesizes current knowledge on the trafficking mechanisms, pathological outcomes, and therapeutic targeting of Cx43 in these three subcellular compartments. We further discuss peptide-based inhibitors (e.g., Gap19, &#x3b1;CT1), small molecules (e.g., tonabersat, danegaptide), and natural product-derived modulators, highlighting challenges in specificity, bioavailability, and clinical translation. By linking compartment-specific functions to distinct disease entities, this review establishes subcellular localization as a central determinant of Cx43 biology and a promising axis for precision medicine.

Fetal complete atrioventricular block (f-CAVB) with ventricular bradycardia of &#x2264;&#x2009;55&#x2009;bpm is associated with increased perinatal mortality. With the goal of increasing perinatal survival of f-CAVB cases, we initiated a delivery room protocol to increase fetal heart rate (HR) and cardiac output using intramuscular and intravenous epinephrine given immediately before Cesarean delivery and prior to umbilical cord clamping. We tested the safety and efficacy of this concept of 'chronotropic rescue' in the delivery management of seven fetuses with f-CAVB meeting fetal HR criteria of &#x2264;&#x2009;55&#x2009;bpm in the 12&#x2009;h prior to delivery. The combination of exogenous epinephrine and delayed umbilical cord clamping increased neonatal HR and stabilized the neonates who received an epicardial pacemaker <&#x2009;24&#x2009;h to 5&#x2009;days after delivery. Based on the findings of this Case Series, chronotropic rescue with delayed umbilical cord clamping may improve survival and should be considered in the perinatal management of high-risk f-CAVB cases with very low fetal HR. &#xa9; 2026 International Society of Ultrasound in Obstetrics and Gynecology.

Anesthetic management of pediatric patients with rare diseases presents substantial perioperative challenges and risks. This study evaluated the clinical competency and specific educational needs of anesthesia practitioners in China regarding the perioperative management of this vulnerable patient population. A cross-sectional survey was conducted from May 2024 and March 2025, involving 2127 anesthesia practitioners across China. Data were collected via a validated anonymous questionnaire and analyzed through descriptive statistics and chi-square tests. Among the 2,127 participants, 93.5% were anesthesiologists and 6.5% were nurse anesthetists. Of these, 43.2% (919/2127) reported previous experience in administering anesthesia to children with rare diseases. Despite this exposure, self-assessed competency levels were notably insufficient. Only 9.0% (191/2127) of respondents reported comprehensive knowledge of pediatric rare diseases, and 15.0% (318/2127) expressed adequate confidence in perioperative management protocols. Objective assessment of specific knowledge domains revealed considerable deficiencies: 14.9% (317/2127) of respondents correctly identified contraindications in muscular dystrophy, 6.6% (141/2127) demonstrated adequate understanding of difficult airway indicators, and merely 3.9% (82/2127) accurately recognized depolarizing agent risks. Comparative analysis between self-rated high-familiarity and low-familiarity groups revealed that direct clinical exposure was significantly associated with practitioners' understanding of pediatric rare diseases. Regarding the development of future anesthesia support systems for pediatric rare diseases, practitioners identified two primary requirements: comprehensive diagnostic information (58.6%, 1246/2127) and detailed anesthesia contraindications (57.0%, 1212/2127). Additionally, 50.1% (1065/2127) of respondents emphasized the importance of real-time knowledge base updates to ensure access to current clinical guidelines and safety protocols. This study highlights substantial knowledge gaps and insufficient confidence among anesthesia practitioners in the perioperative management of children with rare diseases, underscoring an urgent need for enhanced training and robust support systems in this specialized area.

Maternal iron deficiency anemia (iron deficiency anemia) is a persistent global health challenge with increased risk of adverse perinatal outcomes. A recent multicenter clinical trial found reduced rates of low birthweight infants in mothers treated initially (early second trimester) with IV ferric carboxymaltose compared to oral iron. Secondary findings included improved hematologic indices 4 weeks post-treatment, as well as reduced rate of stillbirth with single dose IV iron infusion. We aimed to determine if the initial response to iron therapy was associated with risk of stillbirth and other adverse perinatal outcomes in pregnant singletons with moderate iron deficiency anemia STUDY DESIGN: This is a secondary analysis of a multi-center randomized controlled trial in India that compared single dose intravenous iron to oral iron for the initial management of moderate iron deficiency anemia (Hb 7.0-9.9g/dL) at 14-17 weeks gestation. The primary outcome for this secondary analysis is stillbirth. Secondary outcomes were early preterm birth <34 weeks, small for gestational age infants (<10%ile). The predictors of interest were maternal hemoglobin, ferritin, and transferrin saturation (TSAT), measured at 20-24 weeks gestation. Longitudinal hematologic and iron indices through pregnancy and association with outcomes were also assessed. Relative risk of each outcome based on post-treatment hemoglobin, ferritin, and TSAT was assessed with Poisson regression, adjusting for maternal age, BMI, parity, treatment modality, baseline Hb, and study site. Two-sided alpha=0.05 used for all analyses. Given that most nutrients exhibit U-shaped or threshold risk curves, we also fit models allowing for a quadratic function for the relationship between hematologic parameters at all times and risk of each event RESULTS: 4252 participants were included in this analysis, 1421, 1424, 1407 received intravenous ferric derisolmaltose, ferric carboxymaltose, and oral iron respectively. In evaluating the linear relationship, each unit of increasing Hb response at 20-24 weeks was significantly associated with reduced risk of stillbirth (RR 0.74 (0.56, 0.98). In evaluating the quadratic relationship, we found that there was a significantly progressively increased risk of stillbirth (p<0.0001) and early preterm birth< 34 weeks (p=0.01). Although there was a significant quadratic relationship identified with small for gestational age infant and Hb (p=0.008), the relative risk of SGA and lower Hb was not statistically significant. Inadequate improvement in hemoglobin at 20-24 weeks following iron therapy in pregnancies complicated by moderate iron deficiency anemia is associated with increased risk of stillbirth and early preterm birth. Our findings highlight the potential importance of early screening and treatment of maternal anemia,. Given the association between persistent anemia at 20-24 weeks and adverse outcome, prospective trials should focus on whether early pregnancy, or even preconception, improvement in hemoglobin is an effective intervention to prevent adverse perinatal outcomes such as stillbirth and early preterm birth.

Children born small for gestational age (SGA) face elevated risks of metabolic, cardiovascular, respiratory, and neurodevelopmental disorders, as well as premature mortality, yet the underlying mechanisms remain only partly understood. We analyze blood proteomic data from multiple birth cohorts to identify molecular pathways linked to SGA and to later-life lung function. We find that approximately one-third of SGA children exhibit a distinct molecular endotype marked by dysregulation of axon-guidance proteins in cord blood. In peripheral blood collected later in life, these proteins are inversely associated with contemporaneous spirometric restriction. Using GWAS data and an experimental sheep model, we obtain convergent evidence that axon-guidance genes are associated with spirometric indices (FEV1/FVC) at genome-wide significance and are broadly expressed during fetal development across multiple organs. These findings offer new insight into the developmental origins of chronic disease and highlight axon-guidance pathways as promising targets for investigating multiorgan morbidity.

Alterations of the gut microbiome have been reported in central nervous system demyelinating diseases. While the gut microbiome in pediatric multiple sclerosis (MS) has been studied, the role of the gut microbiome in other pediatric-onset acquired demyelinating syndromes (ADS) remains unknown. We compared the gut microbiome composition between myelin oligodendrocyte glycoprotein antibody-positive (MOG+) and antibody-negative (MOG-) participants with pediatric-onset ADS. Participants aged &#x2264;21 years enrolled in the Canadian Pediatric Demyelinating Disease Network microbiome study (2015-2018) with a single episode or relapsing non-MS, non-neuromyelitis optica spectrum disease attacks of demyelination with symptom onset <18 years were included. Stool sample-derived DNA underwent 16S rRNA (V4) sequencing. Serum MOG-IgG antibodies were tested within 30 days of first attack onset. Alpha-diversity (Shannon, Margalef's index, Chao1) and beta-diversity (weighted UniFrac) were analysed. Phylum/genus-level taxa were assessed using negative binomial models with false discovery rate correction. Rate ratios were sex- and age-adjusted (aRR). Forty-six participants (18 MOG+/28 MOG-) were included. Mean age at stool sample collection (MOG+/MOG-) was 14.7/17.2 years. Alpha-/beta-diversities did not differ between MOG+/MOG- participants (p > 0.3). At the phylum level, the relative abundance of Proteobacteria was lower in MOG+ than MOG- participants (aRR:0.22;95%CI:0.07-0.69;q = 0.03). At the genus level, the relative abundance of Escherichia/Shigella was lower in MOG+ than MOG- participants (aRR:0.01;95%CI:0.001-0.07;q = 0.001), CONCLUSIONS: While alpha/beta-diversities did not differ between MOG+/MOG- participants, taxa-level differences were observed. Our findings suggest that the gut microbiome composition may differ by MOG serostatus among pediatric-onset ADS participants. Future work is warranted, utilizing larger cohorts and longitudinal follow-up.

Vaccine preventable infections (VPIs) contribute substantially to morbidity and mortality in solid organ transplant (SOT) recipients. Recent outbreaks and declining herd immunity have brought attention to optimizing vaccination pre and posttransplant, as many patients remain incompletely immunized at the time of transplant. This review summarizes modern evidence and evolving recommendations regarding live vaccination in SOT candidates and recipients. Vaccination coverage at the time of transplant remains suboptimal, although targeted interventions have shown improvements in uptake. Accumulating data, largely from pediatric liver and kidney SOT cohorts, support the safety and immunogenicity of posttransplant measles, mumps, rubella (MMR) and varicella (VAR) vaccination under defined clinical and immunologic criteria. These findings have informed updated guidance and clinical practice for select pediatric SOT recipients, and multicenter experience with posttransplant live vaccination continues to expand. Growing evidence suggests that live vaccine administration may be feasible in carefully selected pediatric SOT recipients and may reduce susceptibility to VPIs. Important knowledge gaps remain, particularly for adult SOT recipients, nonliver transplant populations, and other live vaccines. Further research and prospective studies are needed to better define safety, immunogenicity, and optimal vaccination timing in these populations.

Proton pump inhibitor (PPI) use has been associated with metabolic dysfunction associated with steatotic liver disease (MASLD) in multiple studies. While the association is confounded by various risk factors, such as BMI and age, a potential mediating factor of the microbiome has been suggested. In this study, we aimed to identify bacterial clades with the highest mediating potential and evaluate the serially mediated path through microbially derived endogenous ethanol. Microbiome mediation analysis of PPI use and MASLD was conducted in two cohorts. In a bariatric surgery cohort (n&#x2009;=&#x2009;122), liver biopsy-proven steatosis grade and postprandial ethanol concentrations were used as outcomes. In the HELIUS cohort (n&#x2009;=&#x2009;2440), a general population cohort study, mediation was performed using the Fatty Liver Index (FLI) score. The strongest associations were validated in the FINRISK cohort (n&#x2009;=&#x2009;7066). Several bacterial taxa, which are predominantly found in the small intestine, showed a potential role in mediating the effects of PPIs on MASLD, postprandial ethanol levels, and FLI score. The Lactobacillales order showed the strongest mediating potential across the outcomes tested in both discovery cohorts. A notable serial mediation pathway was identified, linking PPI use to MASLD via Lactobacillales abundance and postprandial plasma ethanol concentrations. The mediating role of Lactobacillales in the association between PPI use and FLI scores was confirmed in the final study cohort. Data from multiple cross-sectional cohort studies support a mediating potential of the microbiome in the association between PPI use and hepatic steatosis, independent of alcohol consumption. The effect of PPIs on MASLD appears to be mediated mainly by increased lactic acid bacteria abundance, and is potentially, in part, serially mediated by endogenous ethanol production.