Compound heterozygous TMEM67 biallelic variants including a novel frameshift mutation in two Filipino adolescent siblings with Joubert syndrome.

Joubert Syndrome (JS) is a congenital cerebellar ataxia typically inherited in an autosomal recessive pattern, although rare X-linked inheritance can occur. It is characterized by hypotonia evolving into ataxia, global developmental delay, oculomotor apraxia, breathing dysregulation, and multiorgan involvement. To date, there are 40 causative genes implicated in JS, all of which encode proteins of the primary cilium.

Unbound bilirubin and risk of severe neurodevelopmental impairment in extremely low birthweight newborns.

Background: Unbound bilirubin (UB) was measured on day 5 ± 1 in 1101 ELBW newborns in the Aggressive vs Conservative Phototherapy randomized controlled trial. We accessed this dataset to quantify the UB-mediated risk of severe neurodevelopmental impairment (sNDI) in extremely low birthweight (ELBW) newborns.

Methods: UB levels were standardized within laboratories as z-score percentiles.

Distinct pro-inflammatory/pro-angiogenetic signatures distinguish children with Long COVID from controls.

Background: Recent proteomic studies have documented that Long COVID in adults is characterized by a pro-inflammatory signature with thromboinflammation. However, if similar events happen also in children with Long COVID has never been investigated.

Methods: We performed an extensive protein analysis of blood plasma from pediatric patients younger than 19 years of age Long COVID and a control group of children with acute COVID-19, MIS-C, and healthy controls resulted similar for sex distribution and age.

Prenatal Diagnosis of Congenital Heart Disease in Liveborn Infants in the New England Region.

Prenatal diagnosis of congenital heart disease requiring early cardiac catheterization or surgical intervention enables optimal delivery planning for appropriate postnatal cardiovascular intervention and care. This allows for improved morbidity and mortality. Prior national data reported prenatal diagnosis rates of 32% for congenital heart disease requiring intervention in infants in the first 6 months of life in the New England region.

KDIGO 2025 clinical practice guideline for the evaluation, management, and treatment of autosomal dominant polycystic kidney disease (ADPKD): executive summary.

The Kidney Disease: Improving Global Outcomes (KDIGO) 2025 Clinical Practice Guideline for the Evaluation, Management, and Treatment of Autosomal Dominant Polycystic Kidney Disease (ADPKD) represents the first KDIGO guideline on this subject. Its scope includes nomenclature, diagnosis, prognosis, and prevalence; kidney manifestations; chronic kidney disease (CKD) management and progression, kidney failure, and kidney replacement therapy; therapies to delay progression of kidney disease; polycystic liver disease; intracranial aneurysms and other extrarenal manifestations; lifestyle and psychosocial aspects; pregnancy and reproductive issues; pediatric issues; and approaches to the management of people with ADPKD. The guideline has been developed with patient partners, clinicians, and researchers around the world, with the goal to generate a useful resource for healthcare providers and patients by providing actionable recommendations.

Changes in adrenomedullin in bronchoalveolar lavage fluid with chorioamnionitis in a sheep-based model.

Background: Adrenomedullin (AM) is a potent angiogenic, antioxidant and anti-inflammatory peptide protecting the developing lung from injury due to bronchopulmonary dysplasia (BPD) of the preterm infant. At this stage, no data on the potential effects of chorioamnionitis (CA) occurrence and glucocorticoids (GC) administration on AM in developing lungs are still lacking.

Objective: to investigate, in a sheep-based model, the positive/side-effects of combined exposure to CA and GC on AM concentrations measured in bronchoalveolar lavage fluid (BALF).

Phenotypic Heterogeneity of ADTKD-MUC1 Diagnosed Using VNtyper, a Novel Genetic Technique.

Rationale & Objective: Molecular diagnosis of autosomal dominant tubulointerstitial kidney disease (ADTKD) due to variants in the MUC1 gene has long been challenging since variants lie in a large Variable Number of Tandem Repeat (VNTR) region, making identification impossible using standard short read techniques. Previously, we addressed this diagnostic limitation by developing a computational pipeline, named VNtyper, for easier reliable detection of MUC1 VNTR pathogenic variants from short read sequences. This led to unexpected diagnoses of ADTKD-MUC1 among patients with kidney disease referred for genetic testing, which we report here.

Temporal trends and patterns in mortality from falls across 59 high-income and upper-middle-income countries, 1990-2021, with projections up to 2040: a global time-series analysis and modelling study.

Background: Deaths related to falls are a substantial public health problem worldwide, and insight into trends and differences in global fall-related deaths can be valuable for identifying prevention strategies and developing effective policies. Thus, we aimed to estimate global fall-related mortality rate trends and forecast future fall-related deaths.

Methods: In this global time-series analysis and modelling study, we investigated temporal trends in fall-related mortality rates from 1990 to 2021 using the WHO Mortality Database, following the GATHER guidelines, and forecasted trends until 2040 across 59 high-income and upper-middle-income countries.

Incidence and survival of European adolescents and young adults diagnosed with sarcomas: EUROCARE-6 results.

Background: Epidemiological data for sarcoma in adolescents and young adults (AYAs) and across age groups are limited. We aim to: 1) update sarcoma incidence, survival, and changes over time in European AYAs; 2) provide an updated comparison of sarcoma survival in AYAs versus children and mature adults.

Methods: We calculated crude incidence rates (IR) per 100,000 European population per year from 2006 to 2013.

Sex- and trimester-specific impact of gestational co-exposure to organophosphate esters and phthalates on insulin action among preschoolers: Findings from the Ma'anshan birth cohort.

Introduction: Prenatal exposure to organophosphate esters (OPEs) and phthalic acid esters (PAEs) is ubiquitous among pregnant individuals. However, research exploring the relationship between prenatal co-exposure to OPEs and PAEs and childhood insulin function remains limited.

Methods: In this study, utilizing data from 2,246 maternal-fetal dyads in the Ma'anshan Birth Cohort, associations between co-exposure to OPEs and PAEs and insulin action were analyzed.

Evaluation of adherence to the Preferred Reporting of CasE Series in Surgery (PROCESS) 2020 guideline in case series describing endovascular management of vein of Galen malformation demonstrates suboptimal reporting practices.

Background: Interventional neuroradiology is a dynamic field with technological advancements constantly driving evolution in clinical practice. Case series provide interventional neuroradiologists the opportunity to describe the clinical implications of novel equipment and techniques almost in real-time, informing broader adoption and directing future research. Complete reporting in case series is vital in enabling readers to detect bias, determine the generalizability of results and replicate study methodology.

Impact of Subsequent Fellowship on Urology Chief Resident Case Log Volumes.

Objective: To characterize the impact of subsequent fellowship on the case log experience of trainees throughout their residency and specifically their chief resident year.

Materials And Methods: Urology resident case logs from 2010 to 2022 were obtained from 13 institutions for total residency and chief years. Five categorized index procedures were included for analysis: General Urology; Endourology; Reconstructive Urology; Urologic Oncology; and Pediatric Urology.

Evaluation and Management of Congenital Cytomegalovirus Infection.

The purpose of this review is to serve as an update on congenital cytomegalovirus (CMV) evaluation and management for obstetrician-gynecologists and to provide a framework for counseling birthing people at risk for or diagnosed with a primary CMV infection or reactivation or reinfection during pregnancy. A DNA virus, CMV is the most common congenital viral infection and the most common cause of nongenetic childhood hearing loss in the United States. The risk of congenital CMV infection from transplacental viral transfer depends on the gestational age at the time of maternal infection and whether the infection is primary or nonprimary.

Arterial stiffness mediates insulin resistance-related risk of atherosclerotic cardiovascular disease: a real-life, prospective cohort study.

Background: The precise pathways connecting insulin resistance (IR) to atherosclerotic cardiovascular disease (ASCVD) remain undefined. The present study aimed to examine the mediating role of arterial stiffness in the association between IR and ASCVD, providing epidemiology insights into the potential mechanisms driving IR to incident ASCVD.

Methods: A total of 59,777 participants from the Kailuan Study Arterial Stiffness Subcohort who were free of ASCVD at baseline were enrolled in the present study.

Identifying the Minimal Clinically Important Difference in Emotion Regulation Among Youth Using the JoyPop App: Survey Study.

Background: The minimal clinically important difference (MCID) is an important threshold to consider when evaluating the meaningfulness of improvement following an intervention. The JoyPop app is an evidence-based smartphone app designed to improve resilience and emotion regulation. Information is needed regarding the JoyPop app's MCID among culturally diverse youth.

Structured hernia surgery training program for general practitioners in Rwanda - feasibility and evaluation.

Background: Hernias are among the most common surgical conditions worldwide, with significant prevalence in Africa. However, according to recent WHO statistics, Africa faces a critical shortage of trained surgeons. Structured surgical training programs are also scarce.

Conflict at work and incident chronic low back pain: a retrospective cohort of more than 101,000 adults from Germany.

Purpose: Little is known about the relationship between conflict at work and incident chronic low back pain (CLBP). Thus, this retrospective cohort study analyzed the association between conflict at work and the five-year incidence of CLBP in adults living in Germany.

Methods: This study included individuals aged 18-65 years reporting conflict at work for the first time in one of 1,293 general practices in Germany between 2005 and 2022 (index date).

Prescriptions (Rx) for Prevention: Clinical Tools for Integrating Environmental Health into Pediatric Clinical Care.

The integration of environmental health (EH) into routine clinical care for children is in its early stages. The vision of pediatric EH is that all clinicians caring for children are aware of and able to help connect families to needed resources to reduce harmful environmental exposures and increase health-enhancing ones. Environmental exposures include air pollution, substandard housing, lead, mercury, pesticides, consumer products chemicals, drinking water contaminants, industrial facility emissions and, increasingly, climate change-related extreme weather and heat events.

Reduced autoimmunity associated with deletion of host CD73.

CD73 is ubiquitously expressed and regulates critical functions across multiple organ systems. The sequential actions of CD39 and CD73 accomplish the conversion of adenosine triphosphate to adenosine and shift the adenosine triphosphate-driven proinflammatory immune cell milieu toward an anti-inflammatory state. This immunological switch is a major mechanism by which regulatory T (Treg) cells control inflammation.

CD209d/e promotes inflammation and lung injury during influenza virus infection.

Influenza virus infects millions each year, contributing greatly to human morbidity and mortality. Upon viral infection, pathogen-associated molecular patterns activate pattern recognition receptors on host cells, triggering an immune response. The CD209 protein family, homologs of DC-SIGN (dendritic cell-specific intercellular adhesion molecule 3-grabbing nonintegrin), is thought to modulate immune responses to viruses.

Defining a novel DYRK1A-gp130/IL-6R-pSTAT axis that regulates Th17 differentiation.

Dysregulated differentiation of naïve CD4+ T cells into T helper 17 (Th17) cells is likely a key factor predisposing to many autoimmune diseases. Therefore, better understanding how Th17 differentiation is regulated is essential to identify novel therapeutic targets and strategies to identify individuals at high risk of developing autoimmunity. Here, we extend our prior work using chemical inhibitors to provide mechanistic insight into a novel regulator of Th17 differentiation, the kinase dual-specificity tyrosine phosphorylation-regulated kinase 1A (DYRK1A).

Central or Peripheral Venoarterial Extracorporeal Membrane Oxygenation for Pediatric Sepsis: Outcomes Comparison in the Extracorporeal Life Support Organization Dataset, 2000-2021.

Objectives: Small studies of extracorporeal membrane oxygenation (ECMO) support for children with refractory septic shock (RSS) suggest that high-flow (≥ 150 mL/kg/min) venoarterial ECMO and a central cannulation strategy may be associated with lower odds of mortality. We therefore aimed to examine a large, international dataset of venoarterial ECMO patients for pediatric sepsis to identify outcomes associated with flow and cannulation site.

Design: Retrospective analysis of the Extracorporeal Life Support Organization (ELSO) database from January 1, 2000, to December 31, 2021.

Population pharmacokinetic analysis of teicoplanin in paediatric patients, including those receiving continuous kidney replacement therapy: a prospective cohort study.

Objectives: Teicoplanin is a commonly used antibiotic in critically ill children. However, teicoplanin dosing is often inaccurate, especially in children undergoing continuous kidney replacement therapy (CKRT). This study aims to develop a population pharmacokinetic (PK) model to optimize teicoplanin dosing in critically ill children, including those on CKRT.

Heidelberg Adult and Pediatric Airway Registry (HAPA-Registry).

Background: Advanced airway management is of fundamental importance in almost all areas of anesthesiology, emergency medicine, and critical care. Securing the airway is of the utmost importance, as this is a prerequisite for the oxygenation of the human organism. The clinical relevance of airway management is particularly evident in the fact that the primary cause of significant anesthesia-related complications can be attributed to this field.