Telemedicine-based antibiotic stewardship program in pediatrics: study protocol of a stepped wedge cluster randomized trial-the TeleKasper study.

BACKGROUND: Overuse and misuse of antibiotics is one of the driving factors of antimicrobial resistance, a growing global health threat. The use of antibiotics is particularly high in children. Even though the implementation of antibiotic stewardship programs (ASP) in pediatrics has been shown to reduce antibiotic use, this implementation has been limited to large university hospitals in Germany. Telemedicine applications might be an effective approach to implement ASP in non-university settings. METHODS: This protocol details the TeleKasper study (Telemedical Competence Network "Antibiotic Stewardship in Pediatrics"). Tele-Kasper is a stepped-wedge cluster-randomized trial that will be conducted across non-university children's hospitals in Germany. The intervention consists of a telemedical consultation service in the form of a network in different German areas, using an app as a communication tool. The primary outcome will be a 20% reduction in overall antibiotic consumption measured using defined daily doses per 100 patient days. DISCUSSION: The TeleKasper study aims to implement and evaluate a prototype for a nationwide antibiotic stewardship program by telemedical means in pediatric departments in non-university hospitals in Germany to promote rational antibiotic use and improve medical care for infections. TRIAL REGISTRATION: German Clinical Trials Register (DRKS) DRKS00028534. Registered on 22nd of April 2022.

Short-term outcomes of asphyxiated neonates depending on requirement for transfer in the first 24 h of life.

IMPORTANCE: In neonates with birth asphyxia (BA) and hypoxic-ischemic encephalopathy, therapeutic hypothermia (TH), initiated within six hours, is the only safe and established neuroprotective measure to prevent secondary brain injury. Infants born outside of TH centers have delayed access to cooling. OBJECTIVE: To compare in-hospital mortality, occurrence of seizures, and functional status at discharge in newborns with BA depending on postnatal transfer for treatment to another hospital within 24 h of admission (transferred (TN) versus non-transferred neonates (NTN)). DESIGN: Nationwide retrospective cohort study from a comprehensive hospital dataset using codes of the International Classification of Diseases, 10th modification (ICD-10). Clinical and outcome information was retrieved from diagnostic and procedural codes. Hierarchical multilevel logistic regression modeling was performed to quantify the effect of being postnatally transferred on target outcomes. SETTING: All discharges from German hospitals from 2016 to 2021. PARTICIPANTS: Full term neonates with birth asphyxia (ICD-10 code: P21) admitted to a pediatric department on their first day of life. EXPOSURES: Postnatal transfer to a pediatric department within 24 h of admission to an external hospital. MAIN OUTCOMES: In-hospital death; secondary outcomes: seizures and pediatric complex chronic conditions category (PCCC) ≥ 2. RESULTS: Of 11,703,800 pediatric cases, 25,914 fulfilled the inclusion criteria. TNs had higher proportions of organ dysfunction, TH, organ replacement therapies, and neurological sequelae in spite of slightly lower proportions of maternal risk factors. In TNs, the adjusted odds ratios (OR) for death, seizures, and PCCC ≥ 2 were 4.08 ((95% confidence interval 3.41-4.89), 2.99 (2.65-3.38), and 1.76 (1.52-2.05), respectively. A subgroup analysis among infants receiving TH (n = 3,283) found less pronounced adjusted ORs for death (1.67 (1.29-2.17)) and seizures (1.26 (1.07-1.48)) and inverse effects for PCCC ≥ 2 (0.81 (0.64-1.02)) in TNs. CONCLUSION AND RELEVANCE: This comprehensive nationwide study found increased odds for adverse outcomes in neonates with BA who were transferred to another facility within 24 h of hospital admission. Closely linking obstetrical units to a pediatric department and balancing geographical coverage of different levels of care facilities might help to minimize risks for postnatal emergency transfer and optimize perinatal care.

Surgical Site Infections After Pediatric Liver Transplantation-Impact of a Change in Perioperative Prophylactic Antibiotic Protocol.

BACKGROUND: In spite of improved survival rates after pediatric liver transplantation, infections remain major contributors to perioperative morbidity and mortality. This study aimed to understand the impact of type and duration of perioperative antibiotic prophylaxis (PAP) on the occurrence of surgical site infections (SSIs). METHODS: In total, 125 patients who underwent liver transplantation between 2014 and 2020 were retrospectively included. Patients were categorized into two periods based on changes in the standard PAP regimen. Risk factors for SSIs were investigated, including the influence of PAP duration, antibiotic substances used, and abdominal patch placement using multivariable regression models. RESULTS: SSIs occurred in 23 (19%) of 119 analyzed patients and were not impacted by changes in the PAP regimen. The placement of an abdominal patch was a relevant risk factor for SSIs (odds ratio 3.81; 95% confidence interval [CI] 1.15-12.68). Longer PAP duration reduced the occurrence of SSIs by up to 4.6 percentage points (95% CI 0.0-9.1) per day, with its effect diminishing with longer duration. The choice of antibiotic substances for PAP changed after implementation of the new protocol, with a decline in vancomycin usage from 14% to 3%. CONCLUSION: The results of this study emphasize the need for evidence-based PAP regimens tailored to the unique needs of pediatric liver transplant recipients. The occurrence of SSIs remains complex and is influenced by various factors beyond the PAP regimen. Multicentric efforts to develop effective prevention strategies against SSIs in this vulnerable population are warranted.

Association of bilaterally suppressed EEG amplitudes and outcomes in critically ill children.

Background and objectives: Amplitude-integrated EEG (aEEG) is used to assess electrocortical activity in pediatric intensive care if (continuous) full channel EEG is unavailable but evidence regarding the meaning of suppressed aEEG amplitudes in children remains limited. This retrospective cohort study investigated the association of suppressed aEEG amplitudes in critically ill children with death or decline of neurological functioning at hospital discharge. Methods: Two hundred and thirty-five EEGs derived from individual patients <18 years in the pediatric intensive care unit at the University Hospital Essen (Germany) between 04/2014 and 07/2021, were converted into aEEGs and amplitudes analyzed with respect to age-specific percentiles. Crude and adjusted odds ratios (OR) for death, and functional decline at hospital discharge in patients with bilateral suppression of the upper or lower amplitude below the 10th percentile were calculated. Sensitivity, specificity, positive (PPV) and negative predictive values (NPV) were assessed. Results: The median time from neurological insult to EEG recording was 2 days. PICU admission occurred due to neurological reasons in 43% and patients had high overall disease severity. Thirty-three (14%) patients died and 68 (29%) had a functional decline. Amplitude suppression was observed in 48% (upper amplitude) and 57% (lower amplitude), with unilateral suppression less frequent than bilateral suppression. Multivariable regression analyses yielded crude ORs between 4.61 and 14.29 and adjusted ORs between 2.55 and 8.87 for death and functional decline if upper or lower amplitudes were bilaterally suppressed. NPVs for bilaterally non-suppressed amplitudes were above 95% for death and above 83% for pediatric cerebral performance category Scale (PCPC) decline, whereas PPVs ranged between 22 and 32% for death and 49-52% for PCPC decline. Discussion: This study found a high prevalence of suppressed aEEG amplitudes in critically ill children. Bilaterally normal amplitudes predicted good outcomes, whereas bilateral suppression was associated with increased odds for death and functional decline. aEEG assessment may serve as an element for risk stratification of PICU patients if conventional EEG is unavailable with excellent negative predictive abilities but requires additional information to identify patients at risk for poor outcomes.

Correlation of Comfort Score and Narcotrend Index during Procedural Sedation with Midazolam and Propofol in Children.

Background/Objectives: Precise assessment of hypnotic depth in children during procedural sedation with preserved spontaneous breathing is challenging. The Narcotrendindex (NI) offers uninterrupted information by continuous electrocortical monitoring without the need to apply a stimulus with the risk of assessment-induced arousal. This study aimed to explore the correlation between NI and the Comfort Scale (CS) during procedural sedation with midazolam and propofol and to identify an NI target range for deep sedation. Methods: A prospective observational study was conducted on 176 children (6 months to 17.9 years) undergoing procedural sedation with midazolam premedication and continuous propofol infusion. Statistical analyses included Pearson correlation of NI and CS values, logistic regression, and receiver operating curves. Results: Median NI values varied with CS and age. The correlation coefficient between CS and NI was 0.50 and slightly higher in procedure-specific subgroup analyses. The optimal NI cut-off for deep sedation was between 50 and 60 depending on the analyzed subgroup and displayed high positive predictive values for sufficient sedation throughout. Conclusion: Our study found a moderate correlation between NI and CS, demonstrating reliable identification of adequately sedated patients.

Pediatric Community-Acquired Brain Abscesses: A Single-center Retrospective Study.

The European Society for Clinical Microbiology and Infectious Diseases recommends 3rd generation cephalosporins and metronidazole for empirical treatment of community-acquired brain abscesses. In 53 retrospectively analyzed pediatric patients with community-acquired brain abscesses at a German University Hospital Staphylococcus aureus was identified as a relevant pathogen (21%). Therefore, it may be reasonable to cover S. aureus when selecting empirical therapy.

Current practice of intracranial pressure monitoring in children with severe traumatic brain injury-a nationwide prospective surveillance study in Germany.

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.

Clinical recommendations for the inpatient management of lower respiratory tract infections in children and adolescents with severe neurological impairment in Germany.

Children and adolescents with severe neurological impairment (SNI) require specialized care due to their complex medical needs. In particular, these patients are often affected by severe and recurrent lower respiratory tract infections (LRTIs). These infections, including viral and bacterial etiology, pose a significant risk to these patients, often resulting in respiratory insufficiency and long-term impairments. Using expert consensus, we developed clinical recommendations on the management of LRTIs in children and adolescents with SNI. These recommendations emphasize comprehensive multidisciplinary care and antibiotic stewardship. Initial treatment should involve symptomatic care, including hydration, antipyretics, oxygen therapy, and respiratory support. In bacterial LRTIs, antibiotic therapy is initiated based on the severity of the infection, with aminopenicillin plus a beta-lactamase inhibitor recommended for community-acquired LRTIs and piperacillin-tazobactam for patients with chronic lung disease or tracheostomy. Ongoing management includes regular evaluations, adjustments to antibiotic therapy based on pathogen identification, and optimization of supportive care. Implementation of these recommendations aims to improve the diagnosis and treatment of LRTIs in children and adolescents with SNI. What is Known: • Children and adolescents with severe neurological impairment are particularly affected by severe and recurrent lower respiratory tract infections (LRTIs). • The indication and choice of antibiotic therapy for bacterial LRTI is often difficult because there are no evidence-based treatment recommendations for this heterogeneous but vulnerable patient population; the frequent overuse of broad-spectrum or reserve antibiotics in this patient population increases selection pressure for multidrug-resistant pathogens. What is New: • The proposed recommendations provide a crucial framework for focused diagnostics and treatment of LRTIs in children and adolescents with severe neurological impairment. • Along with recommendations for comprehensive and multidisciplinary therapy and antibiotic stewardship, ethical and palliative care aspects are taken into account.

Aortic Steal Correlates with Acute Organ Dysfunction and Short-Term Outcomes in Neonates with Vein of Galen Malformation.

INTRODUCTION: Vein of Galen aneurysmal malformation (VGAM) is a rare, congenital cerebrovascular malformation with high morbidity and mortality. Parameters to foresee clinical progression and allow individualized parent counseling are lacking. The aim of this study was to evaluate aortic steal measured by Doppler ultrasound as a prognostic parameter in these neonates. METHODS: A retrospective monocentric analysis of cardiac ultrasound exams before embolization in neonates with VGAM was conducted. Percentage of aortic steal measured by time-averaged maximum velocity above and below the zero flow baseline by pulsed Doppler ultrasound at the preductal aortic isthmus was calculated. Association of aortic steal with parameters of acute organ dysfunction (Bicêtre neonatal evaluation score [BNES], neonatal multiple organ dysfunction score [NeoMODS]) and mortality and determination of correlation between aortic steal and cerebral damage on initial and follow-up cerebral magnetic resonance imaging (cMRI) were evaluated. RESULTS: Twelve neonates were included, of which 3 died. Per 10 percentage point increase of aortic steal, BNES decreased by 1.64 (95% confidence interval [CI]: 1.28-2.0) points and the maximum observed NeoMODS increased by 1.25 (CI: 0.94-1.57) points. The odds for mortality increased by 2.3 (CI: 1.14-13.67) per 10 percentage point increase of aortic steal. There was a correlation between aortic steal and cerebral damage at baseline (white matter ρ [rho] = 0.34, gray matter ρ = 0.81) and follow-up (white matter ρ = 0.80, gray matter ρ = 0.72). CONCLUSION: The degree of aortic steal in neonates with VGAM was highly associated with the severity of organ dysfunction, disease progression on cMRI, and mortality.

Targeted PCR of Mucorales in pediatric bronchoalveolar lavage samples indicates low prevalence of airway colonization and sample contamination.

Mucorales are a large order of ubiquitous saprophytic zygomycete fungi and act as opportunistic pathogens in humans. In pediatric patients, little is known about the role of Mucorales in airway colonization and infection or their role as contaminants of respiratory samples. Currently, polymerase chain reaction (PCR) is the most sensitive mode of detection Mucorales in clinical specimen. In this study, we aimed to determine the prevalence of Mucorales in bronchoalveolar lavage samples (BAL) from a large, diverse group of pediatric patients. We performed commercial Mucorales PCR (MucorGenius®, Pathonostics, Maastricht, NL, USA) on 102 thawed BAL samples of 100 patients. Mucorales PCR was negative in all samples. Our data suggest that Mucorales spp. have a low prevalence in paediatric airways and do not frequently contaminate pediatric BAL samples.

[Increased rate of complications of pediatric acute otitis media and sinusitis in 2022/2023]. / Häufung von Komplikationen der akuten Otitis media und Sinusitis bei Kindern 2022/2023.

BACKGROUND: Acute mastoiditis and orbital complications of acute rhinosinusitis are among the most common complications of pediatric infections in otolaryngology. OBJECTIVE: The aim of this study was to investigate the frequency of pediatric acute mastoiditis in the setting of acute otitis media as well as pediatric orbital complications in the setting of acute rhinosinusitis. Data from before the pandemic were compared to data after the end of the COVID-19 restrictions. MATERIALS AND METHODS: Included were hospitalized children who presented with acute mastoiditis from acute otitis media or with orbital complications from acute rhinosinusitis during the period from April 2017 to March 2023. Compared were three periods using descriptive statistics: April 2017 to March 2020 (before the pandemic in Germany), April 2020 to March 2022 (during the contact restrictions of the pandemic), and April 2022 to March 2023 (after the contact restrictions were lifted). RESULTS: A total of 102 children (43 with acute mastoiditis, 42%, and 59 with orbital complications of acute sinusitis, 58%) were included. During the 2022/2023 period, more than twice as many children with acute mastoiditis and approximately three times as many children with orbital complications of acute rhinosinusitis were hospitalized compared to the average of the periods 2017/2018, 2018/2019, and 2019/2020. In the 2021/2022 period, the number of these patients was below the average of previous years. CONCLUSION: This year's seasonal cluster of upper respiratory tract infections is associated with a higher-than-average incidence of orbital complications and mastoiditis.

Increased SARS-CoV-2 reactive low avidity T cells producing inflammatory cytokines in pediatric post-acute COVID-19 sequelae (PASC).

BACKGROUND: A proportion of the convalescent SARS-CoV-2 pediatric population presents nonspecific symptoms, mental health problems, and a reduction in quality of life similar to myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and long COVID-19 symptomatic. However, data regarding its clinical manifestation and immune mechanisms are currently scarce. METHODS: In this study, we perform a comprehensive clinical and immunological profiling of 17 convalescent COVID-19 children with post-acute COVID-19 sequelae (PASC) manifestation and 13 convalescent children without PASC manifestation. A detailed medical history, blood and instrumental tests, and physical examination were obtained from all patients. SARS-CoV-2 reactive T-cell response was analyzed via multiparametric flow cytometry and the humoral immunity was addressed via pseudovirus neutralization and ELISA assay. RESULTS: The most common PASC symptoms were shortness of breath/exercise intolerance, paresthesia, smell/taste disturbance, chest pain, dyspnea, headache, and lack of concentration. Blood count and clinical chemistry showed no statistical differences among the study groups. We detected higher frequencies of spike (S) reactive CD4+ and CD8+ T cells among the PASC study group, characterized by TNFα and IFNγ production and low functional avidity. CRP levels are positively correlated with IFNγ producing reactive CD8+ T cells. CONCLUSIONS: Our data might indicate a possible involvement of a persistent cellular inflammatory response triggered by SARS-CoV-2 in the development of the observed sequelae in pediatric PASC. These results may have implications on future therapeutic and prevention strategies.

Fading SARS-CoV-2 humoral VOC cross-reactivity and sustained cellular immunity in convalescent children and adolescents.

Cross-reactive cellular and humoral immunity can substantially contribute to antiviral defense against SARS-CoV-2 variants of concern (VOC). While the adult SARS-CoV-2 cellular and humoral immunity and its cross-recognition potential against VOC is broadly analyzed, similar data regarding the pediatric population are missing. In this study, we perform an analysis of the humoral and cellular SARS-CoV-2 response immune of 32 convalescent COVID-19 children (children), 27 convalescent vaccinated adults(C + V+) and 7 unvaccinated convalescent adults (C + V-). Similarly to adults, a significant reduction of cross-reactive neutralizing capacity against delta and omicron VOC was observed 6 months after SARS-CoV-2 infection. While SAR-CoV-2 neutralizing capacity was comparable among children and C + V- against all VOC, children demonstrated as expected an inferior humoral response when compared to C + V+. Nevertheless, children generated SARS-CoV-2 reactive T cells with broad cross-recognition potential. When compared to V + C+, children presented even comparable frequencies of WT-reactive CD4 + and CD8 + T cells with high avidity and functionality. Taking into consideration the limitations of study - unknown disease onset for 53% of the asymptomatic pediatric subjects, serological detection of SARS-CoV-2 infection-, our results suggest that following SARS-CoV-2 infection children generate a humoral SARS-CoV-2 response with neutralizing potential comparable to unvaccinated COVID-19 convalescent adults as well a sustained SARS-CoV-2 cellular response cross-reactive to VOC.

Distinct clinical phenotypes in paediatric cancer patients with sepsis are associated with different outcomes-an international multicentre retrospective study.

Background: Identifying phenotypes in sepsis patients may enable precision medicine approaches. However, the generalisability of these phenotypes to specific patient populations is unclear. Given that paediatric cancer patients with sepsis have different host response and pathogen profiles and higher mortality rates when compared to non-cancer patients, we determined whether unique, reproducible, and clinically-relevant sepsis phenotypes exist in this specific patient population. Methods: We studied patients with underlying malignancies admitted with sepsis to one of 25 paediatric intensive care units (PICUs) participating in two large, multi-centre, observational cohorts from the European SCOTER study (n = 383 patients; study period between January 1, 2018 and January 1, 2020) and the U.S. Novel Data-Driven Sepsis Phenotypes in Children study (n = 1898 patients; study period between January 1, 2012 and January 1, 2018). We independently used latent class analysis (LCA) in both cohorts to identify phenotypes using demographic, clinical, and laboratory data from the first 24 h of PICU admission. We then tested the association of the phenotypes with clinical outcomes in both cohorts. Findings: LCA identified two distinct phenotypes that were comparable across both cohorts. Phenotype 1 was characterised by lower serum bicarbonate and albumin, markedly increased lactate and hepatic, renal, and coagulation abnormalities when compared to phenotype 2. Patients with phenotype 1 had a higher 90-day mortality (European cohort 29.2% versus 13.4%, U.S. cohort 27.3% versus 11.4%, p < 0.001) and received more vasopressor and renal replacement therapy than patients with phenotype 2. After adjusting for severity of organ dysfunction, haematological cancer, prior stem cell transplantation and age, phenotype 1 was associated with an adjusted OR of death at 90-day of 1.9 (1.04-3.34) in the European cohort and 1.6 (1.2-2.2) in the U.S. cohort. Interpretation: We identified two clinically-relevant sepsis phenotypes in paediatric cancer patients that are reproducible across two international, multicentre cohorts with prognostic implications. These results may guide further research regarding therapeutic approaches for these specific phenotypes. Funding: Part of this study is funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development.

[Time to Antibiotics (TTA) - Reassessment from the German Working Group for Fever and Neutropenia in Children and Adolescents (DGPI/GPOH)]. / Time to Antibiotics (TTA) ­ Überlegungen der Arbeitsgruppe Fieber bei Granulozytopenie im Kindes- und Jugendalter (GPOH/DGPI) zu einer Neubewertung.

BACKGROUND: The current German guidance from 2016 recommends a Time to Antibiotics (TTA) of<60 min in children and adolescents with febrile neutropenia (FN). METHODS: Critical analysis of available studies and recent meta-analyses, and discussion of the practical consequences in the FN working group of the German Societies for Paediatric Oncology and Haematology and Paediatric Infectious Diseases. RESULTS: The available evidence does not support a clinically significant outcome benefit of a TTA<60 min in all paediatric patients with FN. Studies suggesting such a benefit are biased (mainly triage bias), use different TTA definitions and display further methodical limitations. In any case, a TTA<60 min remains an essential component of the 1st hour-bundle in paediatric cancer patients with septic shock or sepsis with organ dysfunction. CONCLUSION: Provided that all paediatric FN patients receive a structured medical history and physical examination (including vital signs) by experienced and trained medical personnel in a timely fashion, and provided that a sepsis triage and management bundle is established and implemented, a TTA lower than 3 hours is sufficient and reasonable in stable paediatric cancer patients with FN.

Outcome after conservative or surgical treatment for new-onset epilepsy in children with cerebral cavernous malformation.

OBJECTIVE: This study aimed to investigate and compare the outcome of conservatively or surgically treated children with cerebral cavernous malformation (CCM) and new-onset CCM-related epilepsy (CRE) during a 5-year period. METHODS: In this observational monocentric cohort study, data were collected ambispectivley. Our database was screened for CCM patients treated between 2003 and 2020. Patients ≤18 years of age with complete magnetic resonance imaging dataset, clinical baseline characteristics, and diagnosis of new-onset CRE were included. Definite seizure control was classified as International League Against Epilepsy class <2. Functional outcome was assessed using the modified Rankin Scale score. CRE patients were separated into two groups according to their treatment modality. Seizure control, intake of antiseizure medication, and functional outcomes were assessed. Systematic literature research was performed to identify other cases of new-onset CRE in children and to compare the collected data with published data. RESULTS: Thirty-nine pediatric CRE patients were analyzed. A total of 18 (46.1%) patients were conservatively treated, while 21 (53.8%) underwent surgical CCM removal. While the functional outcome was similar in both groups at the last follow-up, definite seizure control was better in the surgical group (77.8%) than in the conservative group (25.0%) both after 5-years of follow-up (p = 0.038), and at last follow-up with 85.7% versus 50% respectively (p = 0.035). We found substantially higher rates of discontinuation of antiseizure medication at the last available follow-up in patients undergoing surgical resection (p = 0.009). The systematic literature review identified 4 studies with a total of 30 additional children with early onset CRE. CONCLUSION: Surgical treatment of pediatric patients with new-onset CRE had higher rates of complete seizure control and early discontinuation of antiseizure medication than conservative treatment. Neurological outcomes of patients managed surgically or conservatively were comparable. These results encourage early surgical management of children with CRE even in the absence of pharmacoresistant epilepsy, but randomized control trials are urgently needed for further decision-making.

Giant Cavernous Malformation Mimicking an Infiltrative Intracranial Neoplasm in Children-Case Report and Systematic Review of the Literature.

BACKGROUND: Giant cavernous malformations (GCMs) are rare and poorly characterized neurovascular lesions in adults or children and often misclassified. In this study, we provide a review of pediatric GCM cases to highlight this rare entity as an important differential diagnosis in preoperative assessment. METHODS: We report a pediatric case of GCM that presented as an intracerebral, periventricular, and infiltrative mass lesion. We performed a systematic review of published literature describing cases of GCM in children using the PubMed, Embase, and Cochrane Library databases. Studies describing cerebral or spinal cavernous malformation >4 cm were included. Demographic, clinical, radiographic, and outcome data were extracted. RESULTS: Thirty-eight studies accounting for 61 patients were reviewed. most patients were 1-10 years old and 55.73% were male. Average lesion sizes ranged between 4 and 6 cm (40.98% >6 cm; 8.19% >10 cm). Supratentorial localization was most common (75.40%), with frontal and parieto-occipital regions being frequent localizations. Infratentorial lesions (24.60%) were located within the cerebellum (16.39%) and brainstem (8.19%). One case of spinal cavernoma was found. The main clinical manifestations were seizures (44.26%), focal neurologic deficit (36.06%), and headache (22.95%). Imaging showed contrast enhancement (36.06%), cystic features (27.86%), and infiltrative growth pattern (4.91%). CONCLUSIONS: GCMs show variable clinical and radiologic features, representing a diagnostic challenge for treating surgeons. Imaging may show various tumorlike features such as cystic or infiltrative patterns with contrast enhancement. The existence of GCM should be considered preoperatively. Gross total resection should be attempted whenever possible, because it correlates with a good recovery and long-term outcomes. Also, a clear definition criteria of when a cerebral cavernous malformation is termed giant should be established.

A European International Multicentre Survey on the Current Practice of Perioperative Antibiotic Prophylaxis for Paediatric Liver Transplantations.

(1) Background: Postoperative infections are major contributors of morbidity and mortality after paediatric liver transplantation (pLTX). Evidence and recommendations regarding the most effective antimicrobial strategy are lacking. (2) Results: Of 39 pLTX centres, 20 responded. Aminopenicillins plus ß-lactamase inhibitors were used by six (30%) and third generation cephalosporins by three (15%), with the remaining centres reporting heterogenous regimens. Broad-spectrum regimens were the standard in 10 (50%) of centres and less frequent in the 16 (80%) centres with an infectious disease specialist. The duration ranged mainly between 24-48 h and 3-5 days in the absence and 3-5 days or 6-10 days in the presence of risk factors. Strategies regarding antifungal, antiviral, adjunctive antimicrobial, and surveillance strategies varied widely. (3) Methods: This international multicentre survey endorsed by the European Liver Transplant Registry queried all European pLTX centres from the registry on their current practice of perioperative antibiotic prophylaxis and antimicrobial strategies via an online questionnaire. (4) Conclusions: This survey found great heterogeneity regarding all aspects of postoperative antimicrobial treatment, surveillance, and prevention of infections in European pLTX centres. Evidence-based recommendations are urgently needed to optimise antimicrobial strategies and reduce the spectrum and duration of antimicrobial exposure.

Functional outcome after pediatric cerebral cavernous malformation surgery.

The purpose of this study was to investigate the functional outcome following surgical resection of cerebral cavernous malformations (CCM) in pediatric patients. We screened our institutional database of CCM patients treated between 2003 and 2021. Inclusion regarded individuals younger or equal than 18 years of age with complete clinical baseline characteristics, magnetic resonance imaging dataset, and postoperative follow-up time of at least three months. Functional outcome was quantified using the modified Rankin Scale (mRS) score and assessed at admission, discharge, and last follow-up examination. The primary endpoint was the postoperative functional outcome. As a secondary endpoint, predictors of postoperative functional deterioration were assessed. A total of 49 pediatric patients with a mean age of 11.3 ± 5.7 years were included for subsequent analyses. Twenty individuals (40.8%) were female. Complete resection of the lesion was achieved in 44 patients (89.8%), and two patients with incomplete resection were referred for successive remnant removal. The mean follow-up time after surgery was 44 months (IQR: 13 - 131). The mean mRS score was 1.6 on admission, 1.7 at discharge, and 0.9 at the latest follow-up. Logistic regression analysis adjusted to age and sex identified brainstem localization (aOR = 53.45 [95%CI = 2.26 - 1261.81], p = .014) as a predictor of postoperative deterioration. This study indicates that CCM removal in children can be regarded as safe and favorable for the majority of patients, depending on lesion localization. Brainstem localization implies a high risk of postoperative morbidity and indication for surgery should be balanced carefully. Minor evidence indicates that second-look surgery for CCM remnants might be safe and favorable.

High Prevalence of Alternative Diagnoses in Children and Adolescents with Suspected Long COVID-A Single Center Cohort Study.

BACKGROUND: Long COVID (LC) is a diagnosis that requires exclusion of alternative somatic and mental diseases. The aim of this study was to examine the prevalence of differential diagnoses in suspected pediatric LC patients and assess whether adult LC symptom clusters are applicable to pediatric patients. MATERIALS AND METHODS: Pediatric presentations at the Pediatric Infectious Diseases Department of the University Hospital Essen (Germany) were assessed retrospectively. The correlation of initial symptoms and final diagnoses (LC versus other diseases or unclarified) was assessed. The sensitivity, specificity, negative and positive predictive values of adult LC symptom clusters were calculated. RESULTS: Of 110 patients, 32 (29%) suffered from LC, 52 (47%) were diagnosed with alternative somatic/mental diseases, and 26 (23%) remained unclarified. Combined neurological and respiratory clusters displayed a sensitivity of 0.97 (95% CI 0.91-1.00) and a negative predictive value of 0.97 (0.92-1.00) for LC. DISCUSSION/CONCLUSIONS: The prevalence of alternative somatic and mental diseases in pediatric patients with suspected LC is high. The range of underlying diseases is wide, including chronic and potentially life-threatening conditions. Neurological and respiratory symptom clusters may help to identify patients that are unlikely to be suffering from LC.