Utility of Cardiac Magnetic Resonance in Assessing Arrhythmic Risk in Patients With Nonischemic Cardiomyopathy Undergoing Biventricular Pacing.

BACKGROUND: Nonischemic cardiomyopathy (NICM) is responsible for approximately one-third of heart failure and is associated with significant morbidity and mortality. Recent data suggested the lack of mortality reduction from adding a defibrillator to cardiac resynchronization therapy (CRT) in all patients with NICM. Myocardial fibrosis detected by cardiac magnetic resonance late gadolinium enhancement (CMR-LGE) can help risk stratify patients who would benefit from adding a defibrillator to CRT in this patient population. OBJECTIVES: We aim to assess the relationship between the presence of myocardial fibrosis detected by CMR-LGE and the rate of major arrhythmic events (MAE) that included sustained ventricular tachycardia (VT), appropriate cardiac resynchronization therapy-defibrillator (CRT-D) intervention, ventricular fibrillation (VF), and sudden cardiac death (SCD) in patients with NICM undergoing CRT and to compare all-cause mortality and heart failure improvement between patients receiving cardiac resynchronization therapy-pacing (CRT-P) versus those receiving CRT-D based on the presence of myocardial fibrosis. METHODS: All consecutive patients with NICM satisfying a guideline-directed indication for CRT implantation were included in the study after excluding patients who refused to consent, patients with acute decompensated heart failure, and those contraindicated for a cardiac magnetic resonance (CMR). Patients were divided into two groups based on the presence of fibrosis in cardiac MRI: the LGE/CRT-D group and the No LGE/CRT-P group. They were then followed for 1 year. RESULTS: Sixty patients were enrolled. Sixteen patients (26.6%) developed MAE during the study duration, among those patients, seven had myocardial fibrosis (receiving CRT-D as per protocol), while nine had no myocardial fibrosis (receiving CRT-P as per protocol), (41.2% vs. 20.9%, p = 0.045). The presence of CMR-LGE, regardless of the extent and distribution, predicted MAE with an odds ratio of 2.6 (CI = 1.78-8.9, p = 0.04). The presence of ≥7.5% of myocardial fibrosis by CMR was associated with 54% sensitivity and 100% specificity for MAE in the study population. All-cause mortality was significantly higher in the No LGE/CRT-P group versus the LGE/CRT-D group (15 [34.9%] vs. 2 [11.8%], p = 0.076). CONCLUSION: In patients with NICM candidates for biventricular pacing, the presence of LGE on CMR, irrespective of the extent or segmental pattern, is independently associated with an MAE and is associated with worse heart failure outcomes. However, the absence of LGE did not rule out MAE, and implanting CRT-P based on lack of fibrosis may result in higher all-cause mortality.

Torticollis as a rare, late complication of VP shunt placement in the pediatric population: a case report.

The placement of a ventriculoperitoneal (VP) shunt is a common neurosurgical, pediatric procedure with various, well-documented complications occurring both in the immediate postoperative course of the procedure and at later stages. Pediatric patients need frequent revision surgeries due to body growth as well as implant failure over the course of the years. We report a rare case of a 12-year-old patient, presenting with torticollis, 11 years after the initial placement of a VP shunt. The peripheral tube had to be surgically removed due to the severe movement limitation of the cervical spine area and the tilting of the head. This is the fourth case known to be reported with this rare complication. The calcification of the tube and the formation of a rigid scar tissue along the shunt tube, combined with the body growth, are the suspected mechanisms of this mechanical malfunction of the VP-shunt. The complication could be efficiently addressed through the surgical replacement of the peripheral tube and the transection of the scar tissue in the neck area.

Adaption of neurosurgical resection patterns for pediatric low-grade glioma spanning two decades-Report from the German LGG-studies 1996-2018.

INTRODUCTION: Neurosurgery is considered the mainstay of treatment for pediatric low-grade glioma (LGG); the extent of resection determines subsequent stratification in current treatment protocols. Yet, surgical radicality must be balanced against the risks of complications that may affect long-term quality of life. We investigated whether this consideration impacted surgical resection patterns over time for patients of the German LGG studies. PATIENTS AND METHODS: Four thousand two hundred and seventy pediatric patients from three successive LGG studies (median age at diagnosis 7.6 years, neurofibromatosis (NF1) 14.7%) were grouped into 5 consecutive time intervals (TI1-5) for date of diagnosis and analyzed for timing and extent of first surgery with respect to tumor site, histology, NF1-status, sex, and age. RESULTS: The fraction of radiological LGG diagnoses increased over time (TI1 12.6%; TI5 21.7%), while the extent of the first neurosurgical intervention (3440/4270) showed a reduced fraction of complete/subtotal and an increase of partial resections from TI1 to TI5. Binary logistic regression analysis for the first intervention within the first year following diagnosis confirmed the temporal trends (p < 0.001) and the link with tumor site for each extent of resection (p < 0.001). Higher age is related to more complete resections in the cerebellum and cerebral hemispheres. CONCLUSIONS: The declining extent of surgical resections over time was unrelated to patient characteristics. It paralleled the evolution of comprehensive treatment algorithms; thus, it may reflect alignment of surgical practice to recommendations in respect to age, tumor site, and NF1-status integrated as such into current treatment guidelines. Further investigations are needed to understand how planning, performance, or tumor characteristics impact achieving surgical goals.

The association of COVID-19 pandemic with the increase of sinogenic and otogenic intracranial infections in children: a 10-year retrospective comparative single-center study.

OBJECTIVE: Otitis media and sinusitis are common childhood infections, typically mild with good outcomes. Recent studies show a rise in intracranial abscess cases in children, raising concerns about a link to COVID-19. This study compares a decade of data on these cases before and after the pandemic. METHODS: This retrospective comparative analysis includes pediatric patients diagnosed with otitis media and sinusitis, who later developed intracranial abscesses over the past decade. We collected comprehensive data on the number of cases, patient demographics, symptoms, treatment, and outcomes. RESULTS: Between January 2013 and July 2023, our center identified 10 pediatric patients (median age 11.1years, range 2.2-18.0 years, 60% male) with intracranial abscesses from otitis media and sinusitis. Of these, 7 cases (70%, median age 9.7 years, range 2.2-18.0 years) occurred since the onset of the COVID-19 pandemic, while the remaining 3 cases (30%, median age 13.3 years, range 9.9-16.7 years) were treated before the pandemic. No significant differences were found in otolaryngological associations, surgical interventions, preoperative symptoms, lab findings, or postoperative antibiotics between the two groups. All patients showed positive long-term recovery. CONCLUSION: This study reveals 5-fold increase of pediatric otogenic and sinogenic intracranial abscess cases in the last three-years since the onset of the COVID-19 pandemic. While further investigation is needed, these findings raise important questions about potential connections between the pandemic and the severity of otitis media and sinusitis complications in children. Understanding these associations can improve pediatric healthcare management during infectious disease outbreaks.

Generation of patient-derived pediatric pilocytic astrocytoma in-vitro models using SV40 large T: evaluation of a modeling workflow.

PURPOSE: Although pediatric low-grade gliomas (pLGG) are the most common pediatric brain tumors, patient-derived cell lines reflecting pLGG biology in culture are scarce. This also applies to the most common pLGG subtype pilocytic astrocytoma (PA). Conventional cell culture approaches adapted from higher-grade tumors fail in PA due to oncogene-induced senescence (OIS) driving tumor cells into arrest. Here, we describe a PA modeling workflow using the Simian Virus large T antigen (SV40-TAg) to circumvent OIS. METHODS: 18 pLGG tissue samples (17 (94%) histological and/or molecular diagnosis PA) were mechanically dissociated. Tumor cell positive-selection using A2B5 was perfomed in 8/18 (44%) cases. All primary cell suspensions were seeded in Neural Stem Cell Medium (NSM) and Astrocyte Basal Medium (ABM). Resulting short-term cultures were infected with SV40-TAg lentivirus. Detection of tumor specific alterations (BRAF-duplication and BRAF V600E-mutation) by digital droplet PCR (ddPCR) at defined time points allowed for determination of tumor cell fraction (TCF) and evaluation of the workflow. DNA-methylation profiling and gene-panel sequencing were used for molecular profiling of primary samples. RESULTS: Primary cell suspensions had a mean TCF of 55% (+/- 23% (SD)). No sample in NSM (0/18) and ten samples in ABM (10/18) were successfully transduced. Three of these ten (30%) converted into long-term pLGG cell lines (TCF 100%), while TCF declined to 0% (outgrowth of microenvironmental cells) in 7/10 (70%) cultures. Young patient age was associated with successful model establishment. CONCLUSION: A subset of primary PA cultures can be converted into long-term cell lines using SV40-TAg depending on sample intrinsic (patient age) and extrinsic workflow-related (e.g. type of medium, successful transduction) parameters. Careful monitoring of sample-intrinsic and extrinsic factors optimizes the process.

Heidelberg ETV score to assess success of ETV in patients with occlusive hydrocephalus: a retrospective single-center study.

In aqueduct stenosis, pressure difference below and above level of obstruction leads to bulging of third ventricular floor (TVF) and lamina terminalis (LT). Endoscopic third ventriculocisternostomy (ETV) is the standard treatment in these patients. We tried to assess success of ETV depending on those two radiological changes in aqueduct stenosis. We implemented "Heidelberg ETV score" retrospectively to assess the state of TVF as well as LT in same manner in midsagittal MR image. Every patient had a preoperative, direct, 3-months and one-year postoperative score from -2 to + 2. We correlated the scores to clinical course to decide whether the score is reliable in defining success of ETV. Between 2017-2021, 67 (mean age 25.6 ± 23.9y) patients treated with ETV were included. Success rate of primary and Re-ETVs was 91% over 46.8 ± 19.0 months. A marked shift of score to the left after surgery in success group was noticed through the distribution of score immediate postoperative, 3-months later; 70.2% showed (+ 2) before surgery, 38.9% scored (0) after surgery and 50.9% showed further score drop to (-1) 3 months later, p < 0.001. In cases of failure, there was initial decrease after surgery followed by increase with ETV-failure (mean time to failure: 7.2 ± 5.7 months) in 100%. Significant difference was noticed in Heidelberg score at postoperative 1-year- and failure-MRI follow-up between two groups, p < 0.001. Heidelberg score describes anatomical changes in third ventricle after ETV and can serve in assessment of MR images to define success of the procedure in patients with aqueduct stenosis.

Programmable (proSA®) vs. fixed (SHUNTASSISTANT®) gravitational valves in pediatric patients with hydrocephalus: a 16-year retrospective single-center comparative study with biomechanical analysis.

PURPOSE: In pediatric hydrocephalus (HC) treatment, programmable gravitational valves offer greater flexibility to manage overdrainage during children's growth. However, it remains unclear whether these devices provide better outcomes rather than their precursors. The study assessed the benefit from programmability of gravitational valve, i.e., programmable-SHUNTASSISTANT (proSA®) vs. SHUNTASSISTANT® (SA®). METHODS: Clinical records and imaging of pediatric patients with hydrocephalus of non-tumoral etiology treated with fixed (SA®) or programmable (proSA®) gravitational valves between January 2006 and January 2022 were analyzed in a retrospective single-center study. Valve survival was compared in relation to age and etiology. Lately explanted valves received biomechanical analysis. RESULTS: A total of 391 gravitational valves (254 SA® and 137 proSA®) were inserted in 244 patients (n = 134 males). One hundred thirty-three SA® (52.4%) and 67 proSA® (48.9%) were explanted during a follow-up of 81.1 ± 46.3 months. Valve survival rate at 1 and 5 years with proSA® was 87.6% and 60.6% compared to 81.9% and 58.7% with SA®, with mean survival time 56.4 ± 35.01 and 51.4 ± 43.0 months, respectively (P = 0.245). Age < 2 years at implantation correlated with significantly lower valve survival rates (P < 0.001), while HC etiology showed no significant impact. Overdrainage alone accounted for more SA® revisions (39.8% vs. 3.1%, P < 0.001), while dysfunctions of the adjustment system represented the first cause of valve replacement in proSA® cohort (45.3%). The biomechanical analysis performed on 41 proSA® and 31 SA® showed deposits on the valve's internal surface in 97.6% and 90.3% of cases. CONCLUSION: Our comparative study between proSA® and SA® valves in pediatric HC demonstrated that both valves showed similar survival rates, regardless of etiology but only with young age at implantation. The programmability may be beneficial in preventing sequelae of chronic overdrainage but does not reduce need for valve revision and proSA® valve should be considered in selected cases in growing children older than 2 years.

Arrhythmogenicity of anti-tachycardia pacing in patients with implantable cardioverter defibrillator.

BACKGROUND: Anti-tachycardia pacing therapy (ATP) has shown comparable efficacy to shock therapy in ventricular tachycardia (VT) termination with better quality of life. However, some ATPs may lead to VT acceleration or degeneration to ventricular fibrillation (VF), which will result in more ICD shocks. The aim of this study was to investigate the predictors of VT acceleration by ATP therapy in a real-life patient cohort. RESULTS: We retrospectively reviewed 448 monomorphic VT episodes that required ATP therapy in 60 patients with structural heart diseases implanted with ICD or CRTD. The clinical data of the patients and the episodes' details were evaluated. We found that patients with a higher ejection fraction (EF) were more likely to be cardioverted by ATP therapy (P: 0.024). VT acceleration was more frequent in patients with lower EF (mean 31.24 ± 4.08) compared with the non-accelerated patients with higher EF (mean 37.00 ± 9.4, P: 0.016). The percentage of accelerated episodes was 8.5%. VT episodes with a mean cycle length (CL) < 310 ms are more likely to accelerate (sensitivity 76.3%, specificity 67.7%, PPV value 45%, NPV 86%, and AUC 0.790). There was a statistically significant difference in the accelerated VT episodes as compared to non-accelerated episodes regarding the number of ATP bursts (mean 3.66 ± 2.22 vs. 1.76 ± 1.35, P: < 0.001), ramp (23.7% vs. 4.2%, P: < 0.001), scanning (55.3% vs. 31.3%, P: 0.003) and burst adaptive cycle length (mean 83.55 ± 2.92 vs. 84.64 ± 2.61, P: 0.016). In a multivariate analysis, the VT CL, number of ATP bursts and ramp pacing predicted VT acceleration by ATP therapy. CONCLUSIONS: Ventricular tachycardia in patients with low LV EF and fast VTs with a CL less than 310 ms were more likely to accelerate with ATP therapy. The number of ATP bursts and the use of ramp had a significant effect on VT acceleration. To avoid VT acceleration by ATP therapy, ramp pacing better be avoided, especially in fast VTs, and lesser number of bursts should be delivered.

Neurosurgical morbidity in pediatric supratentorial midline low-grade glioma: Results from the German LGG studies.

Surgical resection is a mainstay of treatment for pediatric low-grade glioma (LGG) within all current therapy algorithms, yet associated morbidity is scarcely reported. As supratentorial midline (SML) interventions are particularly challenging, we investigated the frequency of neurosurgical complications/new impairments aiming to identify their risk factors. Records were retrospectively analyzed from 318 patients with SML-LGG from successive German multicenter LGG studies, undergoing surgery between May 1998 and June 2020. Exactly 537 operations (230 resections, 167 biopsies, 140 nontumor procedures) were performed in 318 patients (54% male, median age: 7.6 years at diagnosis, 9.5 years at operation, 11% NF1, 42.5% optic pathway glioma). Surgical mortality rate was 0.93%. Applying the Drake classification, postoperative surgical morbidity was observed following 254/537 (47.3%) and medical morbidity following 97/537 (18.1%) patients with a 40.1% 30-day persistence rate for newly developed neurological deficits (65/162). Neuroendocrine impairment affected 53/318 patients (16.7%), visual deterioration 34/318 (10.7%). Postsurgical morbidity was associated with patient age <3 years at operation, tumor volume ≥80 cm3 , presence of hydrocephalus, complete resection, surgery in centers with less than median reported tumor-related procedures and during the earlier study period between 1998 and 2006, while the neurosurgical approach, tumor location, NF1 status or previous nonsurgical treatment were not. Neurosurgery-associated morbidity was frequent in pediatric patients with SML-LGG undergoing surgery in the German LGG-studies. We identified patient- and institution-associated factors that may increase the risk for complications. We advocate that local multidisciplinary teams consider the planned extent of resection and surgical skills.

Intracranial arachnoid cysts: What is the appropriate surgical technique? A retrospective comparative study with 61 pediatric patients.

Objective: Symptomatic intracranial arachnoid cysts (ACs) should be treated either through microsurgical (MS) or endoscopic surgical (ES) fenestration. Implantation of cysto-peritoneal shunt (CPS) system is another treatment option with decreasing indication. In our study, we compared the complication and revision rates between the three operative techniques in pediatric patients. Methods: We included patients below 18 years with symptomatic intracranial ACs operated between 2004 and 2021. Initial symptoms, location, complication rate, clinical and radiological improvement, postoperative events and revision rate were compared retrospectively. Results: Sixty-one patients; 33 (54.1%) MS operated (mean age 7.6 years), 18 (29.5%) ES operated (mean age 6.2 years) and 10 (16.4%) with CPS (mean age 3.0 years) were collected. The most common initial symptom was headache in 45.9%. 20 (32.8%) postoperative events were documented. The highest revision rate (60%) was seen in the CPS group compared to 33.3% in MS group and 16.7% in ES group. 31 patients harbored perisylvian ACs, 89% remained event-free after ES, 71% after MS and 20% after CPS. Clinical improvement immediately after surgery was observed in 58 patients (96.9% in MS, 88.9% in ES and 100% in CPS). A radiological volume reduction could be proven postoperative in 51 patients (78.8% MS, 88.9% ES and 90% CPS). Conclusion: Endoscopic fenestration of AC is a safe and efficient technique which is being widely used nowadays with the highest event free survival compared to microsurgical fenestration especially in perisylvian arachnoid cysts. CPS shows on long terms the highest revision rate but carries the least surgical risks.

Cerebellar Mutism Syndrome After Posterior Fossa Tumor Surgery in Children-A Retrospective Single-Center Study.

OBJECTIVE: Cerebellar mutism syndrome (CMS) is a well-known complication after posterior fossa tumor surgery in pediatric patients. We evaluated the incidence of CMS in our institute and analyzed its association with multiple risk factors, such as tumor entity, surgical approach, and hydrocephalus. METHODS: All pediatric patients who had undergone intra-axial tumor resection in the posterior fossa between January 2010 and March 2021 were included in the retrospective analysis. Various data points, including demographic, tumor-associated, clinical, radiological, surgery-associated, complications, and follow-up data, were collected and statistically evaluated for an association with CMS. RESULTS: A total of 63 surgeries in 60 patients were included. The median patient age was 8 years. Pilocytic astrocytoma was the most common tumor type (50%), followed by medulloblastoma (28%) and ependymomas (10%). Complete, subtotal, and partial resection was achieved in 67%, 23%, and 10%, respectively. A telovelar approach had been used the most often (43%) compared with a transvermian approach (8%). Of the 60 children, 10 (17%) had developed CMS and showed marked improvement but with residual deficits. The significant risk factors were a transvermian approach (P = 0.03), vermian splitting when added to another approach (P = 0.002), an initial presentation with acute hydrocephalus (P = 0.02), and hydrocephalus present after tumor surgery (P = 0.004). CONCLUSIONS: Our CMS rate is comparable to those described in the literature. Despite the limitations of the retrospective study design, we found that CMS was not only associated with a transvermian approach but was also associated with a telovelar approach, although to a lesser extent. Acute hydrocephalus at the initial presentation necessitating urgent management was significantly associated with a greater incidence of CMS.

Initial Clinical Experience and Biomechanical Analysis of a Novel Gravity Unit-Assisted Valve (M.blue) in Pediatric Patients With Hydrocephalus: A Retrospective Study With Two Years of Follow-up.

BACKGROUND: Overdrainage is a widely reported complication representing common indication for shunt revision. Despite recent advances in valve design, repeated shunt revisions represent burden on healthcare systems. OBJECTIVE: To investigate the efficiency of a novel gravity unit-assisted programmable valve "M.blue" in pediatric hydrocephalus using clinical and biomechanical analyses. METHODS: Thisretrospective single-center study included pediatric patients who received M.blue valve between April 2019 and 2021. Several clinical and biomechanical parameters were documented including complications and revision rates. Flow rate, functional assessment in vertical and horizontal positions, and extent of depositions inside valve were analyzed in explanted valves. RESULTS: Thirty-seven M.blue valves in 34 pediatric patients with hydrocephalus (mean age 2.82 ± 3.91 years) were included. Twelve valves (32.4%) were explanted during a follow-up period of 27.3 ± 7.9 months. One-year survival rate of 89% and overall survival rate of 67.6% with a valve survival average of 23.8 ± 9.7 months were observed. Patients with explanted valves (n = 12) were significantly younger, with 0.91 ± 0.54 years of age in average ( P = .004), and showed significantly more adjustments difficulties ( P = .009 ). 58.3% of explanted valves showed deposits in more than 75% of the valve surface despite normal cerebrospinal fluid findings and were associated with dysfunctional flow rate in vertical, horizontal, or both positions. CONCLUSION: The novel M.blue valve with integrated gravity unit is efficient in pediatric hydrocephalus with comparable survival rate. Deposits inside valves could affect its flow rate in different body positions and might lead to dysfunction or difficulties in valve adjustments.

Infants With Trigonocephaly Treated With Fronto-Orbital Remodelling and Endocortical Positioning of Resorbable Plates-A Retrospective Cohort Study Including 101 Patients.

PURPOSE: Fronto-orbital remodeling is the gold standard for surgical treatment of metopic synostosis in many craniofacial centers. For fixation, resorbable materials are widely used. Because of swelling during resorption, the positioning of the plates can be relevant. Therefore, the goal of this study was to investigate whether there are limitations to endocortical positioning of resorbable plates. METHODS: In this retrospective study, all patients with metopic craniosynostosis resulting in trigonocephaly, who were treated with a standardized fronto-orbital remodeling and endocortical positioning of resorbable plates, between February 2012 and December 2019 were included. The endpoint of this study was the postoperative complications that can be attributed to the material used. RESULTS: A total of 101 patients, who were treated at our unit, could be included with a male predominance, 81 (80.2%) boys versus 20 (19.8%) girls. Surgery was performed at a median age of 9 months (±2.56). No complications were seen related to resorbable plates. All patients of our study population were categorized as Whitaker classification I and II. CONCLUSION: This study shows that the risk level in using endocortical resorbable plates positioned on the inner surface of the bone is low. From an aesthetic point of view, we could not detect any disadvantage.

Adverse events in neurosurgery: a comprehensive single-center analysis of a prospectively compiled database.

PURPOSE: To prospectively identify and quantify neurosurgical adverse events (AEs) in a tertiary care hospital. METHODS: From January 2021 to December 2021, all patients treated in our department received a peer-reviewed AE-evaluation form at discharge. An AE was defined as any event after surgery that resulted in an undesirable clinical outcome, which is not caused by the underlying disease, that prolonged patient stay, resulted in readmission, caused a new neurological deficit, required revision surgery or life-saving intervention, or contributed to death. We considered AEs occurring within 30 days after discharge. AEs were categorized in wound event, cerebrospinal fluid (CSF) event, CSF shunt malfunction, post-operative infection, malpositioning of implanted material, new neurological deficit, rebleeding, and surgical goal not achieved and non-neurosurgical AEs. RESULTS: 2874 patients were included. Most procedures were cranial (45.1%), followed by spinal (33.9%), subdural (7.7%), CSF (7.0%), neuromodulation (4.0%), and other (2.3%). In total, there were 621 AEs shared by 532 patients (18.5%). 80 (2.8%) patients had multiple AEs. Most AEs were non-neurosurgical (222; 8.1%). There were 172 (6%) revision surgeries. Patients receiving cranial interventions had the most AEs (19.1%) although revision surgery was only necessary in 3.1% of patients. Subdural interventions had the highest revision rate (12.6%). The majority of fatalities was admitted as an emergency (81/91 patients, 89%). Ten elective patients had lethal complications, six of them related to surgery (0.2%). CONCLUSION: This study presents the one-year results of a prospectively compiled AE database. Neurosurgical AEs arose in one in five patients. Although the need for revision surgery was low, the rate of AEs highlights the importance of a systematic AE database to deliver continued high-quality in a high-volume center.

Inappropriate shocks following recent generator replacement.

In a 64-year-old male patient with an implantable cardioverter defibrillator (ICD) for secondary prevention of sudden cardiac death, a shock occurred some months after generator exchange and downgrade to a single-chamber system. Careful analysis of the stored electrogram revealed a rare cause that could be confirmed at the time of operative revision.

ShuntScope-Guided Versus Free-Hand Technique for Ventricular Catheter Placement: A Retrospective Comparative Study of Intraventricular Catheter Tip Position and Complication Rate.

BACKGROUND: The position of the ventricular catheter (VC) is essential for a proper function of cerebrospinal fluid diversion system. A ShuntScope-guided (SG) method might be helpful in reducing complications. The purpose of this study is to compare the accuracy of catheter placement and the complication and revision rates between SG and free-hand (FH) techniques. METHODS: This is a retrospective study based on a prospectively acquired database of patients who underwent VC placement between September 2018 and July 2021. Accuracy of catheter placement was graded on postoperative imaging using the 3-point Hayhurst grading system. Complication and revision rates were documented and compared between both groups with an average follow-up period of 20.84 months. RESULTS: Fifty-seven patients were included. The SG technique was used in 29 patients (mean age was 6.3 years, 1.4-27.7 years, 48.1% females), and the FH technique was used in 28 patients (mean age was 26.7 years, 0.83-79.5 years, 67.9% female). The success rate for the optimal placement of the VC with grade I on the Hayhurst scale was significantly higher in the SG group (93.1%) than in the FH group (60.7%), p = 0.012. The revision rate was higher in the FH group with 35.7% versus 20.7% in the SG group, p = 0.211. CONCLUSION: VC placement using the SG technique is a safe and effective procedure, which enabled a significantly higher success rate and lower revision and complication rate. Accordingly, we recommend using the SG technique especially in patients with difficult anatomy.

BH3 mimetics targeting BCL-XL impact the senescent compartment of pilocytic astrocytoma.

BACKGROUND: Pilocytic astrocytoma (PA) is the most common pediatric brain tumor and a mitogen-activated protein kinase (MAPK)-driven disease. Oncogenic MAPK-signaling drives the majority of cells into oncogene-induced senescence (OIS). While OIS induces resistance to antiproliferative therapies, it represents a potential vulnerability exploitable by senolytic agents. METHODS: We established new patient-derived PA cell lines that preserve molecular features of the primary tumors and can be studied in OIS and proliferation depending on expression or repression of the SV40 large T antigen. We determined expression of anti-apoptotic BCL-2 members in these models and primary PA. Dependence of senescent PA cells on anti-apoptotic BCL-2 members was investigated using a comprehensive set of BH3 mimetics. RESULTS: Senescent PA cells upregulate BCL-XL upon senescence induction and show dependency on BCL-XL for survival. BH3 mimetics with high affinity for BCL-XL (BCL-XLi) reduce metabolic activity and induce mitochondrial apoptosis in senescent PA cells at nano-molar concentrations. In contrast, BH3 mimetics without BCL-XLi activity, conventional chemotherapy, and MEK inhibitors show no effect. CONCLUSIONS: Our data demonstrate that BCL-XL is critical for survival of senescent PA tumor cells and provides proof-of-principle for the use of clinically available BCL-XL-dependent senolytics.

Long-term follow-up of surgical intervention pattern in pediatric low-grade gliomas: report from the German SIOP-LGG 2004 cohort.

OBJECTIVE: Neurosurgical treatment is an integral part of the treatment algorithms for pediatric low-grade glioma (LGG), yet patterns of surgical procedures are rarely challenged. The objective of this study was to evaluate surgical treatment patterns in pediatric LGG. METHODS: The German Societé Internationale d'Oncologie Pédiatrique (SIOP)-LGG 2004 cohort was analyzed to identify relevant patient and tumor characteristics associated with time to death, next surgery, number of resections, and radiological outcome. RESULTS: A total of 1271 patients underwent 1713 neurosurgical interventions (1 intervention in 947, 2 in 230, 3 in 70, and 4-6 in 24). The median age of the study population was 8.57 years at first surgery, and 46.1% were female. Neurofibromatosis type 1 (NF1) was found in 4.4%, and 5.4% had tumor dissemination. Three hundred fifty-four patients (27.9%) had chemotherapy and/or radiotherapy. The cumulative incidence of second surgery at 10 years was 26%, and was higher for infants, those with spinal and supratentorial midline (SML) tumors, and those with pilomyxoid astrocytomas. The hazard ratio for subsequent surgery was higher given dissemination and noncomplete initial resection, and lower for caudal brainstem and SML tumors. Among 1225 patients with fully documented surgical records and radiological outcome, 613 reached complete remission during the observation period, and 50 patients died. Patients with pilocytic astrocytoma had higher chances for a final complete remission, whereas patients with initial partial or subtotal tumor resection, dissemination, NF1, or primary tumor sites in the spinal cord and SML had lower chances. CONCLUSIONS: Neurosurgery is a key element of pediatric LGG treatment. In almost 50% of the patients, however, at least some tumor burden will remain during long-term follow-up. This study found that most of these patients reached a stable disease status without further surgeries. Multidisciplinary team decisions must balance the goal of complete resection, risk factors, repeated surgeries, and possible treatment alternatives in a wide range of heterogeneous entities. Procedural details and neurological outcome should be recorded to better assess their impact on long-term outcome.

Thrombocytopenia: is it a prognostic factor for development of post-hemorrhagic hydrocephalus in neonates?

PURPOSE: Post-hemorrhagic hydrocephalus (PHH) is a rare but serious complication among premature babies in the neonatal intensive care unit. The causes of PHH are still not entirely understood, and its prevention and treatment are controversial. We tried to analyze the risk factors for such complication in our cohort. METHODS: We reviewed our neonatology data bank and included all preterms below 28 weeks who were born in the period between 1999 and 2014 and suffered from an intraventricular hemorrhage (IVH). We reviewed gestational age, gender, birth weight, type of birth, IVH degree, comorbidities, therapy, complications, time to event, protein content of cerebrospinal fluid, and clinical follow-up. RESULTS: We identified 180 patients, divided into two subgroups, "B1" with 37 cases (IVH + PHH) and "B2" with 143 cases (IVH - PHH). In group B1, the presence of IVH grades I, II, III, or IV was in 11%, 19%, and 70% respectively. Nineteen patients were treated with a ventricular access device (VAD) or external ventricular drain (EVD). A total of 20 shunts were implanted, with 11 revisions (55%). One patient suffered from thrombocytopenia. In subgroup B2, 51% showed IVH grade I, whereas severe IVH grades were only present in 22%. 25.9% suffered from thrombocytopenia. Thrombocytopenia was significantly higher in patients who did not develop PHH (p value: 0.002). CONCLUSION: According to our results, thrombocytopenia could play a decisive role in avoiding development of PHH as a sequel of IVH. We recommend a randomized controlled trial to assess the possible efficacy of antiplatelet drugs in avoiding PHH in this vulnerable group.