From molecular signatures to radiomics: tailoring neurooncological strategies through forecasting of glioma growth.

OBJECTIVE: Contemporary oncological paradigms for adjuvant treatment of low- and intermediate-grade gliomas are often guided by a limited array of parameters, overlooking the dynamic nature of the disease. The authors' aim was to develop a comprehensive multivariate glioma growth model based on multicentric data, to facilitate more individualized therapeutic strategies. METHODS: Random slope models with subject-specific random intercepts were fitted to a retrospective cohort of grade II and III gliomas from the database at Kepler University Hospital (n = 191) to predict future mean tumor diameters. Deep learning-based radiomics was used together with a comprehensive clinical dataset and evaluated on an external prospectively collected validation cohort from University Hospital Zurich (n = 9). Prediction quality was assessed via mean squared prediction error. RESULTS: A mean squared prediction error of 0.58 cm for the external validation cohort was achieved, indicating very good prognostic value. The mean ± SD time to adjuvant therapy was 28.7 ± 43.3 months and 16.1 ± 14.6 months for the training and validation cohort, respectively, with a mean of 6.2 ± 5 and 3.6 ± 0.7, respectively, for number of observations. The observed mean tumor diameter per year was 0.38 cm (95% CI 0.25-0.51) for the training cohort, and 1.02 cm (95% CI 0.78-2.82) for the validation cohort. Glioma of the superior frontal gyrus showed a higher rate of tumor growth than insular glioma. Oligodendroglioma showed less pronounced growth, anaplastic astrocytoma-unlike anaplastic oligodendroglioma-was associated with faster tumor growth. Unlike the impact of extent of resection, isocitrate dehydrogenase (IDH) had negligible influence on tumor growth. Inclusion of radiomics variables significantly enhanced the prediction performance of the random slope model used. CONCLUSIONS: The authors developed an advanced statistical model to predict tumor volumes both pre- and postoperatively, using comprehensive data prior to the initiation of adjuvant therapy. Using radiomics enhanced the precision of the prediction models. Whereas tumor extent of resection and topology emerged as influential factors in tumor growth, the IDH status did not. This study emphasizes the imperative of advanced computational methods in refining personalized low-grade glioma treatment, advocating a move beyond traditional paradigms.

Tailored Intraoperative MRI Strategies in High-Grade Glioma Surgery: A Machine Learning-Based Radiomics Model Highlights Selective Benefits.

BACKGROUND AND OBJECTIVES: In high-grade glioma (HGG) surgery, intraoperative MRI (iMRI) has traditionally been the gold standard for maximizing tumor resection and improving patient outcomes. However, recent Level 1 evidence juxtaposes the efficacy of iMRI and 5-aminolevulinic acid (5-ALA), questioning the continued justification of iMRI because of its associated costs and extended surgical duration. Nonetheless, drawing from our clinical observations, we postulated that a subset of intricate HGGs may continue to benefit from the adjunctive application of iMRI. METHODS: In a prospective study of 73 patients with HGG, 5-ALA was the primary technique for tumor delineation, complemented by iMRI to detect residual contrast-enhanced regions. Suboptimal 5-ALA efficacy was defined when (1) iMRI detected contrast-enhanced remnants despite 5-ALA's indication of a gross total resection or (2) surgeons observed residual fluorescence, contrary to iMRI findings. Radiomic features from preoperative MRIs were extracted using a U2-Net deep learning algorithm. Binary logistic regression was then used to predict compromised 5-ALA performance. RESULTS: Resections guided solely by 5-ALA achieved an average removal of 93.14% of contrast-enhancing tumors. This efficacy increased to 97% with iMRI integration, albeit not statistically significant. Notably, for tumors with suboptimal 5-ALA performance, iMRI's inclusion significantly improved resection outcomes (P-value: .00013). The developed deep learning-based model accurately pinpointed these scenarios, and when enriched with radiomic parameters, showcased high predictive accuracy, as indicated by a Nagelkerke R2 of 0.565 and a receiver operating characteristic of 0.901. CONCLUSION: Our machine learning-driven radiomics approach predicts scenarios where 5-ALA alone may be suboptimal in HGG surgery compared with its combined use with iMRI. Although 5-ALA typically yields favorable results, our analyses reveal that HGGs characterized by significant volume, complex morphology, and left-sided location compromise the effectiveness of resections relying exclusively on 5-ALA. For these intricate cases, we advocate for the continued relevance of iMRI.

Frequency and characteristics of bacterial and viral low-grade infections of the intervertebral discs: a prospective, observational study.

STUDY DESIGN: Monocentric, prospective, observational study. OBJECTIVE: The clinical relevance of bacterial colonization of intervertebral discs is controversial. This study aimed to determine a possible relationship between bacterial and viral colonization and low-grade infection of the discs. METHODS: We investigated 447 disc samples from 392 patients. Microbiological culture was used to examine the samples for bacterial growth, polymerase chain reaction (PCR) was used for detection of herpes simplex virus types 1 and 2 (HSV-1, HSV-2) and Cytomegalovirus (CMV), and histopathological analysis was used to detect signs of inflammation. The results were compared between subgroups organized according to gender, age, location of the samples, surgical approach, preoperative C-reactive protein (CRP), preoperative and 6 months postoperative Oswestry Disability Index (ODI) and Neck Disability Index (NDI), and Modic changes (MC) of the corresponding endplates. Also, we assessed the occurrence of postoperative infections within 6 months. RESULTS: Microbiological culture was positive in 38.78% of the analyzed intervertebral discs. Altogether, 180 bacteria were isolated. Coagulase-negative staphylococci (CONS) (23.41%) and Cutibacterium acnes (18.05%) were the most frequently detected microorganisms. None of HSV-1, HSV-2, or CMV were detected. Male patients (p = 0.00036) and cervical segments (p = 0.00001) showed higher rates of positive culture results. Ventral surgical approaches ( p < 0.001) and Type 2 MC (p = 0.0127) were significantly associated with a positive microbiological result ( p< 0.001). Neither pre- nor postoperative ODI and NDI are associated with positive culture results. In 4 (1.02%) patients, postoperative spondylodiscitis occurred. CONCLUSIONS: With 447 segments from 392 patients, we present one of the largest studies to date. While disc degeneration caused by HSV-1, HSV-2, and CMV seems unlikely, we found positive microbiological culture results in 38.78% of all discs. The role of local skin flora and sample contamination should be the focus of further investigations. LEVEL OF EVIDENCE: III. TRIAL REGISTRATION: The study was registered at ClinicalTrials.gov (ID: NCT04712487, https://www. CLINICALTRIALS: gov/ct2/show/study/NCT04712487 ).

Morphological Relation of Peripheral Nerve Sheath Tumors and Nerve Fascicles: Prospective Study and Classification.

Removal of benign peripheral nerve sheath tumors (bPNST) represents a surgical challenge. The morphological relation of bPNST and healthy nerve fascicles are of utmost importance for achieving both removal of the entire tumor and preservation of functional integrity of the peripheral nerve. Thus, we intraoperatively assessed the morphological patterns between bPNST and nerve fascicles using photo documentation obtained between January 2009 and September 2021. In 31 patients (20 women and 11 men) with a mean age of 48 ± 18 years a total of 34 bPNST were removed. Four constant morphological patterns between bPNST relatively to nerve fascicles were detected: (1) bPNST is located peripherally (n = 16), (2) it splits the nerve into two main fascicles (n = 5), (3) it totally splits up the nerve out of the nerve's center (n = 8) und (4) it encloses the nerve and its fascicles (n = 5) without any detectable boundary layer. Histology revealed 28 schwannomas, five neurofibromas, and one perineurioma. The proposed classification reflects the increasing complexity of tumor removal with a higher type number. This might be beneficial for preoperative diagnostics, i.e., high-resolution ultrasound or MRI-tractography, as well as for planning the bPNST's surgical resection and the possible need for nerve reconstruction.

Accidental Dural Tears in Minimally Invasive Spinal Surgery for Degenerative Lumbar Spine Disease.

Background: One of the most frequent complications of spinal surgery is accidental dural tears (ADTs). Minimal access surgical techniques (MAST) have been described as a promising approach to minimizing such complications. ADTs have been studied extensively in connection with open spinal surgery, but there is less literature on minimally invasive spinal surgery (MISS). Materials and Methods: We reviewed 187 patients who had undergone degenerative lumbar spinal surgery using minimally invasive spinal fusions techniques. We analyzed the influence of age, Body Mass Index (BMI), smoking, diabetes, and previous surgery on the rate of ADTs in MISS. Results: Twenty-two patients (11.764%) suffered from an ADT. We recommended bed rest for two and a half to 5 days, depending on the type of repair required and the amount of cerebrospinal fluid (CSF) leakage. We could not find any statistically significant correlation between ADTs and age (p = 0.34,), BMI (p = 0.92), smoking (p = 0.46), and diabetes (p = 0.71). ADTs were significantly more frequent in cases of previous surgery (p < 0.001). None of the patients developed a transcutaneous CSF leak or post-operative infection. Conclusions: The frequency of ADTs in MISS appears comparable to that encountered when using open surgical techniques. Additionally, MAST produces less dead space along the corridor to the spine. Such reduced dead space may not be enough for pseudomeningocele to occur, cerebrospinal fluid to accumulate, and fistula to form. MAST, therefore, provides a certain amount of protection.