Stereochemical Heterogeneity Analysis of Polylactides by Multidimensional Liquid Chromatography.

A new and robust high-performance liquid chromatography (HPLC) method that separates poly(lactic acid) (PLA) according to its stereochemical composition is presented. Using this method, poly(l-lactide) incorporating trace amounts of meso-lactide resulting from the racemization is separated from the pristine polymer. To prove this aspect in more detail, a representative poly(l-lactic acid) standard, assumed to be highly homogeneous, was separated using this method. The result showed that this was not the case as a fraction incorporating meso-lactide due to racemization occurring during the synthesis is separated. Employing two-dimensional liquid chromatography (2D-LC), the molar mass differences of the separated species were investigated, and fractions with similar molecular sizes were detected, confirming that the LC separation is solely based on stereochemical heterogeneity. The sample was further fractionated by preparative HPLC, followed by an in-depth analysis of the fractions using homonuclear decoupling in proton nuclear magnetic resonance (1H NMR). Convincing results that unveiled significant differences in the stereochemistry of the isolated PLA fractions were obtained. Subsequent analysis by matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS) also confirmed oligomer series with different end group structures, indicating that the applied HPLC method is very sensitive to minor variations in stereochemistry and end groups. This integrated approach offers detailed insight into the structural characteristics of PLA polymers, contributing to a better understanding of their composition and potential applications.

Rapid DNA methylation-based classification of pediatric brain tumors from ultrasonic aspirate specimens.

BACKGROUND: Although cavitating ultrasonic aspirators are commonly used in neurosurgical procedures, the suitability of ultrasonic aspirator-derived tumor material for diagnostic procedures is still controversial. Here, we explore the feasibility of using ultrasonic aspirator-resected tumor tissue to classify otherwise discarded sample material by fast DNA methylation-based analysis using low pass nanopore whole genome sequencing. METHODS: Ultrasonic aspirator-derived specimens from pediatric patients undergoing brain tumor resection were subjected to low-pass nanopore whole genome sequencing. DNA methylation-based classification using a neural network classifier and copy number variation analysis were performed. Tumor purity was estimated from copy number profiles. Results were compared to microarray (EPIC)-based routine neuropathological histomorphological and molecular evaluation. RESULTS: 19 samples with confirmed neuropathological diagnosis were evaluated. All samples were successfully sequenced and passed quality control for further analysis. DNA and sequencing characteristics from ultrasonic aspirator-derived specimens were comparable to routinely processed tumor tissue. Classification of both methods was concordant regarding methylation class in 17/19 (89%) cases. Application of a platform-specific threshold for nanopore-based classification ensured a specificity of 100%, whereas sensitivity was 79%. Copy number variation profiles were generated for all cases and matched EPIC results in 18/19 (95%) samples, even allowing the identification of diagnostically or therapeutically relevant genomic alterations. CONCLUSION: Methylation-based classification of pediatric CNS tumors based on ultrasonic aspirator-reduced and otherwise discarded tissue is feasible using time- and cost-efficient nanopore sequencing.

Transplant nephrectomy: indication, surgical approach and complications-experiences from a single transplantation center.

PURPOSE: Management of a failed kidney allograft, and the question whether it should be removed is a challenging task for clinicians. The reported risks for transplant nephrectomy (TN) vary, and there is no clear recommendation on indications or surgical approach that should be used. This study gives an overview of indications, compares surgical techniques, and identifies risk factors for higher morbidity. METHODS: Retrospective analysis was conducted on all transplant nephrectomies performed between 2005 and 2020 at Charité Hospital Berlin, Department of Urology. Patient demographics, laboratory parameters, graft survival data, indication for TN, and surgical complications were extracted from medical reports. RESULTS: A total of 195 TN were performed, with graft intolerance syndrome being the most common indication in 52 patients (26.7%), acute rejection in 36 (18.5%), acute infection in 30 (15.4%), and other reasons to stop immunosuppression in 26 patients (13.3%). Rare indications were vascular complications in 16 (8.2%) and malignancies in the allograft in six (3.1%) cases. Extracapsular surgical approach was significantly more often used in cases of vascular complications and earlier allograft removal, but there was no difference in complication rates between extra- and intracapsular approach. Acute infection was identified as an independent risk factor for a complication grade IIIb or higher according to Clavien-Dindo classification, with a HR of 12.3 (CI 2.2-67.7; p = 0.004). CONCLUSION: Transplant nephrectomy should only be performed when there is a good indication, and non-elective surgery should be avoided, when possible, as it increases morbidity.

Surgical options of chiasmatic hypothalamic glioma-a relevant part of therapy in an interdisciplinary approach for tumor control.

OBJECTIVE: The extent of resection of pediatric low-grade glioma mostly improves progression-free survival. In chiasmatic hypothalamic glioma (CHG), complete resections are limited due to the relevantly high risk of associated neurological and endocrinological deficits. Still, surgery might have its role in the framework of a multidisciplinary team (MDT) approach. We report our retrospective experience from two centers on surgical options and their impact on long-term outcomes. METHODS: Medical records of surgically treated pediatric CHG patients between 2004 and 2022 were analyzed. Patient characteristics, surgical interventions, histology, and non-surgical therapy were retrieved together with outcome measures such as visual acuity, endocrine function, and survival. RESULTS: A total of 63 patients (33 female, NF-1, n = 8) were included. Age at first diagnosis was 4.6 years (range 0.2-16.9) and cohort follow-up was 108 ± 72 months. Twenty patients were surgically treated with a biopsy and 43 patients with debulking at a median age of 6.5 years (range 0.16-16.9). Patients received a median of 2 tumor surgeries (range 1-5). Cyst drainage was accomplished in 15 patients, and 27 patients had ventriculoperitoneal shunt implantation. Non-surgical therapy was given in 69.8%. At the end of follow-up, 74.6% of patients had stable disease. The cohort had a median Karnofsky score of 90 (range 0-100). Four patients died. Hormone substitution was necessary in 30.2%, and visual acuity was impaired in 66% of patients. CONCLUSION: Pediatric CHG is a chronic disease due to overall high survival with multiple progressions. Surgical therapy remains a key treatment option offering biopsy, limited tumor-debulking, cyst fenestration, and hydrocephalus management in the framework of MDT decision-making. Team experience contributes to reducing possible deficits in this challenging cohort.

Stented endoscopic third ventriculostomy: technique, safety, and indications-a multicenter multinational study.

PURPOSE: Endoscopic third ventriculostomy (ETV) is an effective treatment for obstructive hydrocephalus. Secondary stoma closure may be life threatening and is the most common reason for late ETV failure, mostly secondary to local scarring. Local stents intended to maintain patency are rarely used. In this study, we summarize our experience using stented ETV (sETV), efficacy, and safety. MATERIAL AND METHODS: Data was retrospectively collected from all consecutive patients who underwent ETV with stenting at four centers. Collected data included indications for using sETV, hydrocephalic history, surgical technique, outcomes, and complications. RESULTS: Sixty-seven cases were included. Forty had a primary sETV, and 27 had a secondary sETV (following a prior shunt, ETV, or both). The average age during surgery was 22 years. Main indications for sETV included an adjacent tumor (n = 15), thick or redundant tuber cinereum (n = 24), and prior ETV failure (n = 16). Fifty-nine patients (88%) had a successful sETV. Eight patients failed 11 ± 8 months following surgery. Reasons for failure included obstruction of the stent, reabsorption insufficiency, and CSF leak (n = 2 each), and massive hygroma and tumor spread (n = 1 each). Complications included subdural hygroma (n = 4), CSF leak (n = 2), and stent malposition (n = 1). There were no complications associated with two stent removals. CONCLUSION: Stented ETV appears to be feasible and safe. It may be indicated in selected cases such as patients with prior ETV failure, or as a primary treatment in cases with anatomical alterations caused by tumors or thickened tuber cinereum. Future investigations are needed to further elucidate its role in non-communicating hydrocephalus.

Navigated bedside implantation of external ventricular drains with mobile health guidance: technical note and case series.

PURPOSE: External ventricular drain (EVD) implantation is one of the fundamental procedures of emergency neurosurgery usually performed freehand at bedside or in the operating room using anatomical landmarks. However, this technique is frequently associated with malpositioning leading to complications or dysfunction. Here, we describe a novel navigated bedside EVD insertion technique, which is evaluated in a clinical case series with the aim of safety, accuracy, and efficiency in neurosurgical emergency settings. METHODS: From 2021 to 2022, a mobile health-assisted navigation instrument (Thomale Guide, Christoph Miethke, Potsdam, Germany) was used alongside a battery-powered single-use drill (Phasor Health, Houston, USA) for bedside EVD placement in representative neurosurgical pathologies in emergency situations requiring ventricular cerebrospinal fluid (CSF) relief and intracranial pressure (ICP) monitoring. RESULTS: In all 12 patients (8 female and 4 male), navigated bedside EVDs were placed around the foramen of Monro at the first ventriculostomy attempt. The most frequent indication was aneurysmal subarachnoid hemorrhage. Mean operating time was 25.8 ± 15.0 min. None of the EVDs had to be revised due to malpositioning or dysfunction. Two EVDs were converted into a ventriculoperitoneal shunt. Drainage volume was 41.3 ± 37.1 ml per day in mean. Mean length of stay of an EVD was 6.25 ± 2.8 days. Complications included one postoperative subdural hematoma and cerebrospinal fluid infection, respectively. CONCLUSION: Combining a mobile health-assisted navigation instrument with a battery-powered drill and an appropriate ventricular catheter may enable and enhance safety, accuracy, and efficiency in bedside EVD implantation in various pathologies of emergency neurosurgery without adding relevant efforts.

Tailored Concept for Accurate Neuroendoscopy: A Comparative Retrospective Single-Center Study on Image-Guided Neuroendoscopic Procedures.

OBJECTIVE: Precise planning and execution is key for neuroendoscopic interventions, which can be based on different available aiding technologies. The aim of this retrospective study is to report a case-based use of guided neuroendoscopy and to develop a stratification algorithm for the available technologies. METHODS: We reviewed consecutive neuroendoscopic cases performed at our center from 2016 to 2018. We distinguished between patients receiving a new burr hole (group A) and those with a preexisting burr hole (group B). Case-specific technical requirements for procedure planning and execution, complication rate, surgical outcome, and possible subsequent surgery were evaluated. From this experience, a stratification system was developed to tailor the available guiding technologies. RESULTS: A total of 309 neuroendoscopic interventions in 243 patients were included in the present study. The cases included hydrocephalic (81.6%) and nonhydrocephalic (18.4%) conditions. The interventions were supported by coordinate-based (group A, n = 49; group B, n = 67), guide-based (group A, n = 42; group B, n = 0), ultrasound-guided (group A, n = 50; group B, n = 7), or navigated augmented reality-guided (group A, n = 85; group B, n = 9) techniques. The overall complication rate was 4.5%. Stratified by the surgical indication, fontanel status, entry point localization, presence of a preexisting burr hole, ventricular size, and number of targets, an approach toward image-guided neuroendoscopy is suggested. CONCLUSIONS: Planning and technical guidance is essential in neuroendoscopic procedures. The stratified decision-making algorithm for different available technologies aims to achieve lower cost and time consumption, which was found to be safe and efficient. Further investigations are warranted to deliver solid data on procedure efficiency.

Mini-Implant Insertion Using a Guide Manufactured with Computer-Aided Design and Computer-Aided Manufacturing in an Adolescent Patient Suffering from Tooth Eruption Disturbance.

Due to dental diseases, anatomical restrictions, and mixed dentition, the reduction in the number of teeth and the displacement of tooth germs pose challenges in orthodontic treatment, limiting anchorage options. The presented case demonstrates an advanced treatment solution using digital CAD/CAM-technologies and medical imaging for the creation of a mini-implant template. A 12-year-old male patient experiencing delayed tooth eruption, multiple impacted germs, and maxillary constriction underwent intraoral scanning and CBCT. Utilizing coDiagnostiXTM Version 10.2 software, the acquired data were merged to determine the mini-implant placement and to design the template. The template was then manufactured through stereolithography using surgical-guide material. Mini-implants were inserted using the produced appliance, enabling safe insertion by avoiding vital structures. Surgically exposed displaced teeth were aligned using a Hyrax screw appliance anchored on the mini-implants for rapid palatal expansion (RPE) and subsequently used as fixed orthodontics to align impacted teeth. The screw was activated daily for 10 weeks, resulting in a 7 mm posterior and 5 mm anterior maxillary transversal increase. Skeletal anchorage facilitated simultaneous RPE and tooth alignment, ensuring accuracy, patient safety, and appliance stability. The presented case shows a scenario in which computer-aided navigation for mini-implant positioning can enhance precision and versatility in challenging anatomical cases.

Influence of malocclusion and orthodontic treatment in the masticatory efficiency of patients with craniofacial disorders.

This study evaluates masticatory efficiency in orthodontic patients with craniofacial disorders compared to controls without, considering the effect of an orthodontic appliance and malocclusion. A total of 119 participants (7-21 years), divided into a craniofacial disorder and control group (n = 42 and n = 77; mean age 13.5 ± 5.2 and 14.2 ± 3.3 years) were included. Masticatory efficiency was evaluated using a standard food model test, where masticated test food bodies were analyzed, and parameters like particle number (n) and area (mm2) were recorded. This study newly introduced the masticatory efficiency index (MEI), which encompasses the above terms (number and area), with a high MEI being an indicator of high masticatory ability. Younger orthodontic patients with a craniofacial disorder had a significantly decreased MEI (0.50 ± 0.25 n/mm2) compared to patients without (1.10 ± 0.48 n/mm2; p = 0.02). The presence of a crossbite significantly decreased masticatory efficiency, particularly in craniofacial disorder patients (0.69 ± 1.44 n/mm2) versus controls (0.89 ± 1.00 n/mm2, p = 0.04). As treatment progressed with age and fixed appliances, mastication group differences became non-significant, suggesting that patients with a craniofacial disorder were catching up to healthy controls in the rehabilitation of their masticatory function. Considering an early diagnosis of malocclusion during orthodontic therapy in combination with speech therapy can avoid negative malocclusion effects with growth, caused by muscle imbalances.

A European multicenter outcome study on the different perioperative airway management policies following midface surgery in syndromic craniosynostosis: a proposal for a Standard Operating Procedure.

BACKGROUND: Perioperative airway management following midface advancements in children with Apert and Crouzon/Pfeiffer syndrome can be challenging, and protocols often differ. This study examined airway management following midface advancements and postoperative respiratory complications. METHODS: A multicenter, retrospective cohort study was performed to obtain information about the timing of extubation, perioperative airway management, and respiratory complications after monobloc / le Fort III procedures. RESULTS: Ultimately, 275 patients (129 monobloc and 146 Le Fort III) were included; 62 received immediate extubation and 162 delayed extubation; 42 had long-term tracheostomies and nine perioperative short-term tracheostomies. Short-term tracheostomies were in most centers reserved for selected cases. Patients with delayed extubation remained intubated for three days (IQR 2 - 5). The rate of no or only oxygen support after extubation was comparable between patients with immediate and delayed extubation, 58/62 (94%) and 137/162 (85%) patients, respectively. However, patients with immediate extubation developed less postoperative pneumonia than those with delayed, 0/62 (0%) versus 24/161 (15%) (P = 0.001), respectively. Immediate extubation also appeared safe in moderate/severe OSA since 19/20 (95%) required either no or only oxygen support after extubation. The odds of developing intubation-related complications increased by 21% with every extra day of intubation. CONCLUSIONS: Immediate extubation following midface advancements was found to be a safe option, as it was not associated with respiratory insufficiency but did lead to fewer complications. Immediate extubation should be considered routine management in patients with no/mild OSA and should be the aim in moderate/severe OSA after careful assessment.