Background and Objective: The melanocortin-4 receptor agonist setmelanotide compensates for upstream gene defects in the brain leptin-melanocortin pathway and reduces hyperphagia and obesity in selected monogenic obesity forms and Bardet-Biedl syndrome (BBS). We aimed to evaluate the short-term impact of setmelanotide treatment in BBS presenting original real-world data focusing on metabolic dysfunction-associated steatotic liver disease (MASLD) and kidney function. Methods: This monocentric, prospective observational cohort study was performed between June and December 2023 and included patients above the age of 6 years with genetically confirmed BBS, obesity, and/or hyperphagia and planned setmelanotide therapy. Ultrasound examination of the liver including shear wave elastography, dispersion and attenuation imaging (ATI), a bioimpedance analysis, and a hyperphagia questionnaire survey were applied in addition to clinical data collection. Results: Twenty-six patients with BBS (mean age 19.2 years, range [6.2; 51.8]; mean body mass index (BMI) z-score 2.95, range [1.32; 4.84]) were included. All were classified with MASLD (54% S3, 23% each S1 and S2). After 6 months of setmelanotide treatment, estimated glomerular filtration rate increased up to 10.1 mL/min/1.73 m² (95% confidence interval (CI) [4.3; 15.9]). The following parameters also improved: BMI z-score −0.5 (95% CI [−0.6; −0.3]); hyperphagia score −12.3 (95% CI [−15.5; −9.0]); total body fat −3.1% (95% CI [−5.7; −0.5]); ATI −0.14 dB/cm/MHZ (95% CI [−0.17; −0.11]). A total of 85% of patients exhibited either resolution of MASLD or stabilization at grade S1. MASLD improvement correlated only with liver size, not BMI reduction. Conclusion: Setmelanotide treatment is associated with improvement of MASLD independent of BMI reduction as well as increased glomerular filtration rate in BBS.

The performance of injury severity scores (ISSs), used widely to quantify injury severity and predict outcomes, has not been investigated in German pediatric cases. This study aims to identify the most feasible and accurate injury score predictor of mortality in German children with trauma using International Classification of Diseases 10 (ICD-10). Between 2014 and 2020, a retrospective observational cohort study of hospital admissions cases aged <18 years with injury-related ICD-10 codes, using the German hospital database (GHD), was conducted. The maximum abbreviated injury scale and ISS were calculated using the International Classification of Diseases-Abbreviated Injury Scale (ICD-AIS) map provided by the Association for the Advancement of Automotive Medicine, adjusted to the German modification of the ICD-10 classification. The survival risk ratio was used to calculate the single-worst ICD-derived injury (single International Classification of Disease Injury Severity Score [ICISS]) and a multiplicative ICISS. Logistic regressions were conducted for each of the four above-mentioned scores (predictors) to predict in-hospital mortality (outcome) in the selected trauma population and within four clinically relevant subgroups using discrimination and calibration. 1,720,802 were trauma patients, and ICD-AIS mapping was possible in 1,328,377 cases. Cases with mapping failure (n = 392,425; 22.8%) were younger and had a higher mortality rate were excluded from the performance analysis. ICISS-derived scores had a better discrimination and calibration than ICD-AIS based scores in the overall cohort and all four subgroups (area under the curve [AUC] ranges between 0.985 and 0.998 vs 0.886 and- 0.972, respectively). Empirically derived measures of injury severity were superior to ICD-AIS mapped scores in the GHD to predict mortality in pediatric trauma patients. Given the high percentage of mapping failure and high mortality among cases with single-coded injury, the single ICISS may be the most suitable measure of injury severity in this group of patients.

Background: For management of severe traumatic brain injuries (sTBI) in children, the overall level of evidence to guide diagnostic and therapeutic procedures is low. Since 2016, international guidelines have subsequently suggested invasive intracranial pressure (ICP) monitoring in patients with initial Glasgow Coma Scale (GCS) ≤8. In Germany, ICP monitoring was an individual case decision from 2011 until the 2022 update of the German pediatric TBI guideline. The aim of this study was to evaluate current clinical practice of invasive ICP monitoring in Germany in children <10 years with respect to guideline recommendations.Methods: Anonymized clinical data on sTBI cases <10 years of age were collected in a nationwide prospective surveillance study via the German Pediatric Surveillance Unit ESPED from July 2019 until June 2022. Inclusion criteria for the surveillance study were sTBI (initial GCS ≤8) or neurosurgery following TBI. For this analysis, only cases with GCS ≤8 were subject to the present analysis. Descriptive analyses were performed to assess the proportion of ICP monitored patients and describe the cohort.Results: Out of 217 reported cases, 102 cases met the inclusion criteria and thus qualified for ICP monitoring. Of these, 37 (36%) received ICP monitoring. Monitored patients were older, had lower median GCS values at presentation (4 vs. 5), higher mortality (32% vs. 22%), and were more frequently diagnosed with cerebral edema (68% vs. 37%).Conclusion: In children <10 years with sTBI, the present clinical management regarding ICP monitoring deviates from the current German national and international guidelines. The reasons remain unclear, with the low level of evidence in the field of ICP monitoring and the recency of changes in guideline recommendations as potential contributors. Prospective interventional studies should elucidate the benefit of ICP monitoring and ICP directed therapies to provide evidence-based recommendations on ICP monitoring.

Objective Our study aimed to identify the superior predictor of mortality from International Classification of Diseases 10 (ICD-10) codes among pediatric trauma patients in the German hospital database (GHD), a nationwide database comprising all hospitalizations in the country. Study design and setting Hospital admissions of patients aged < 18 years with injury-related ICD-10 codes were selected. The maximum abbreviated injury scale (MAIS) and injury severity score (ISS) were calculated using the ICD-AIS map provided by the Association for the Advancement of Automotive Medicine, which we adjusted to the German modification of the ICD-10 classification. The survival risk ratio was used to calculate the single worst ICD-derived injury (single ICISS) and a multiplicative injury severity score (multiplicative ICISS). The ability to predict mortality of the four above mentioned scores were compared in the selected trauma population and within four clinically relevant subgroups using discrimination and calibration. Results Out of 13,992,596 cases < 18 years of age hospitalized between 2014 and 2020, 1,720,802 were trauma patients and ICD-AIS mapping was possible in 1,328,377 cases. Mortality was highest in patients with only one coded injury. Cases with mapping failure (n = 392,425; 22.8 %) were younger and had a higher mortality rate. SRR-derived scores had a better discrimination calibration than ICD-AIS based scores in the overall cohort and all four subgroups (AUC ranges between 0.985 and 0.998 versus 0.886 and 0.972 respectively). Conclusion Empirically derived measures of injury severity were superior to ICD-AIS mapped scores in the GHD to predict mortality in pediatric trauma patients. Given the high percentage of mapping failure and high mortality among cases with single coded injury, the single ICISS may be the most suitable measure of injury severity in this group of patients.

Introduction: Decompressive craniectomy (DC) is a last tier to control refractory intracranial pressure elevation in children with severe traumatic brain injury (sTBI), but the optimal timing is unknown. This study aimed to describe the association between timing of DC and in-hospital mortality in children with sTBI in Germany. Methods: A retrospective cohort study of the German national hospital discharge database (2016-2022) was conducted for cases < 18 years. Children undergoing DC following sTBI were extracted. Time from admission to DC were calculated as complete hours and data were compared between early (time to DC ≤ 2 hours) and late DC (> 2 hours). Hierarchical logistic regression models evaluated the association of DC timing with in-hospital mortality, functional outcomes (Pediatric Complex Chronic Conditions (PCCC) ≥2)), poor outcome (composite outcome of death or PCCC≥2), length of hospital stay, days on mechanical ventilation (MV) and coding of seizures. Results: Among 13,492,821 children hospitalized, 9,495 had sTBI. DC was performed in 598 cases with time to decompression ranging from 0 to 27 days. More than half of DCs (54.8%) were performed within the first two hours after admission. 164 (27.6%) deaths occurred, with a median time from admission to death of 2 days. Early DC had a higher case-fatality (37.4%) compared to late DC (15.8%), with higher odds of death (adjusted odds ratio [OR] 2.89; 95% confidence interval [95%CI] 1.43-5.85) and poor outcome (OR 1.22; 95% CI 0.71-2.21). However, in survivors, early DC was associated with a shorter duration of MV. No differences in functional outcomes were associated with the timing of DC. Conclusion: Children undergoing early DC exhibited a higher risk of case fatality and poor outcome, alongside with less days on MV in survivors. Key points: Question: Is there an association between the timing of decompressive craniectomy (DC) and in-hospital mortality in children with severe traumatic brain injury (sTBI)? Finding: Early DC (≤ 2 hours after admission) was associated with higher case fatality and poor outcomes but fewer days on mechanical ventilation in survivors compared to late DC (> 2 hours). Meaning: The timing of DC may impact survival and recovery outcomes in pediatric sTBI, suggesting the need to balance early intervention with potential risks.

Background: Tracheostomies are increasingly performed in children. The treatment of infections in tracheostomized patients is challenging because of the distinction between chronic colonization and acute infection. Next‐generation sequencing (NGS) is a promising alternative for identifying and quantifying pathogens in a short period. This study investigated the utility of NGS of tracheal aspirates from healthy and tracheostomized children (TC). Methods: This monocentric prospective case‐control study recruited children with long‐term TC and compared the colonization of the lower airways with a control group of children who had undergone elective general surgery. Tracheal aspirates were analyzed using three methods: bacterial culture, polymerase chain reaction (PCR), and NGS. Results: In total, 107 children were recruited for this study. Sixty‐two samples were excluded due to acute exacerbation, lack of tracheal secretion, or insufficient cfDNA concentration (< 0.3 ng/µl). Consequently, 45 samples (17 controls and 28 tracheotomized samples) were analyzed. Tracheal aspirates analyzed using NGS revealed a significantly higher prevalence of Pseudomonas aeruginosa ( p = 0.0001), Staphylococcus aureus ( p = 0.002), Stenotrophomonas maltophilia ( p = 0.004), and Moraxella catarrhalis ( p = 0.03) in TC. Through NGS, we were able to demonstrate that Pseudomonas aeruginosa was the dominant bacterium in 44% of the samples in which it was detected. Conclusions: NGS can effectively identify a wide spectrum of DNA‐based pathogens (bacteria, viruses, and fungi) in the tracheal aspirates of children. Tracheostomized children were significantly more likely to be colonized by difficult‐to‐treat bacteria. Future research is required to evaluate the clinical benefits of NGS compared with standard microbiological procedures.