Differentiation of multiple brain metastases and glioblastoma with multiple foci using MRI criteria.

OBJECTIVE: Glioblastoma with multiple foci (mGBM) and multiple brain metastases share several common features on magnetic resonance imaging (MRI). A reliable preoperative diagnosis would be of clinical relevance. The aim of this study was to explore the differences and similarities between mGBM and multiple brain metastases on MRI. METHODS: We performed a retrospective analysis of 50 patients with mGBM and compared them with a cohort of 50 patients with multiple brain metastases (2-10 lesions) histologically confirmed and treated at our department between 2015 and 2020. The following imaging characteristics were analyzed: lesion location, distribution, morphology, (T2-/FLAIR-weighted) connections between the lesions, patterns of contrast agent uptake, apparent diffusion coefficient (ADC)-values within the lesion, the surrounding T2-hyperintensity, and edema distribution. RESULTS: A total of 210 brain metastases and 181 mGBM lesions were analyzed. An infratentorial localization was found significantly more often in patients with multiple brain metastases compared to mGBM patients (28 vs. 1.5%, p < 0.001). A T2-connection between the lesions was detected in 63% of mGBM lesions compared to 1% of brain metastases. Cortical edema was only present in mGBM. Perifocal edema with larger areas of diffusion restriction was detected in 31% of mGBM patients, but not in patients with metastases. CONCLUSION: We identified a set of imaging features which improve preoperative diagnosis. The presence of T2-weighted imaging hyperintensity connection between the lesions and cortical edema with varying ADC-values was typical for mGBM.

Endoscope-enhanced fluorescence-guided microsurgery increases survival in patients with glioblastoma.

PURPOSE: Extent of resection (EOR) predicts progression-free survival (PFS) and may impact overall survival (OS) in patients with glioblastoma. We recently demonstrated that 5-aminolevulinic acid-(5-ALA)-fluorescence-enhanced endoscopic surgery increase the rate of gross total resection. However, it is hitherto unknown whether fluorescence-enhanced endoscopic resection affects survival. METHODS: We conducted a retrospective single-center analysis of a consecutive series of patients who underwent surgery for non-eloquently located glioblastoma between 2011 and 2018. All patients underwent fluorescence-guided microscopic or fluorescence-guided combined microscopic and endoscopic resection. PFS, OS, EOR as well as clinical and demographic parameters, adjuvant treatment modalities, and molecular characteristics were compared between microscopy-only vs. endoscopy-assisted microsurgical resection. RESULTS: Out of 114 patients, 73 (65%) were male, and 57 (50%) were older than 65 years. Twenty patients (18%) were operated on using additional endoscopic assistance. Both cohorts were equally distributed in terms of age, performance status, lesion location, adjuvant treatment modalities, and molecular status. Gross total resection was achieved in all endoscopy-assisted patients compared to about three-quarters of microscope-only patients (100% vs. 75.9%, p=0.003). The PFS in the endoscope-assisted cohort was 19.3 months (CI95% 10.8-27.7) vs. 10.8 months (CI95% 8.2-13.4; p=0.012) in the microscope-only cohort. OS in the endoscope-assisted group was 28.9 months (CI95% 20.4-34.1) compared to 16.8 months (CI95% 14.0-20.9), in the microscope-only group (p=0.001). CONCLUSION: Endoscope-assisted fluorescence-guided resection of glioblastoma appears to substantially enhance gross total resection and OS. The strong effect size observed herein is contrasted by the limitations in study design. Therefore, prospective validation is required before we can generalize our findings.

Targeted Epidural Blood Patch Injection Through a Mini-Open Approach for Treatment of Spontaneous Intracranial Hypotension.

BACKGROUND AND OBJECTIVES: Spontaneous intracranial hypotension is recognized as a cause for refractory headache. Treatment can range from blind blood patch injection to microsurgical repair of the cerebrospinal fluid (CSF) leak. The objective of the study was to investigate the safety and efficacy of the targeted blood patch injection (TBPI) technique through a mini-open approach in treatment of refractory intracranial hypotension. METHODS: We retrospectively reviewed cases of 20 patients who were treated for spontaneous intracranial hypotension at our institute between 2011 and 2022. Head and spine MRI and whole-spine myelography were performed in an attempt to localize the CSF leak. All patients underwent implantation of two epidural drains above and beneath the index level through a minimally invasive interlaminar microsurgical approach under general anesthesia. Then, blood patch was injected under clinical surveillance. Treatment success and surgical complications were evaluated postoperatively and at follow-up. RESULTS: Patients presented with orthostatic headache, vertigo, sensory deficits, and hypacusis (95%, 15%, 15%, and 10%, respectively). Subdural effusions were present in 65% of the cases. A CSF leak was identified in all patients. The exact site of the CSF leak could be identified in 80% of cases. TBPI was performed with an average blood amount of 37.5 mL. A significant improvement of symptoms was reported in 90% of the cases. A total of 15% of the patients showed recurrent symptoms and underwent a second TBPI, resulting in symptom relief. No therapy-related complications were reported. CONCLUSION: TBPI is a safe and efficient treatment for spontaneous intracranial hypotension. It is performed in a minimally invasive procedure and can be repeated, if necessary, with a very low-risk profile.

Liquid Biopsy in Low-Grade Glioma: A Systematic Review and a Proposal for a Clinical Utility Score.

Liquid biopsy research on Low-Grade gliomas (LGG) has remained less conspicuous than that on other malignant brain tumors. Reliable serum markers would be precious for diagnosis, follow- up and treatment. We propose a clinical utility score (CUS) for biomarkers in LGG that mirrors their clinical usefulness. We conducted a PRISMA review. We examined each biomarker classifying them by CUS and Level of Evidence (LOE). We identified four classes of biomarkers: (1). Circulating protein-(a) vitronectin discriminates LGG from HGG (Sn:98%, Sp:91%, CUS: 3, LOE: III), (b) CTLA-4 discriminates LGG from HGG, (cutoff: 220.43 pg/ml, Sn: 82%, Sp: 78%, CUS:3, LOE:III), (c) pre-operative TGF b1 predict astrocytoma (cutoff: 2.52 ng/ml, Sn: 94.9%, Sp: 100%, CUS:3, LOE:VI). (2). micro-RNA (miR)-(a) miR-16 discriminates between WHO IV and WHO II and III groups (AUC = 0.98, CUS:3, LOE: III), (b) miR-454-3p is higher in HGG than in LGG (p = 0.013, CUS:3, LOE: III), (c) miR-210 expression is related to WHO grades (Sn 83.2%, Sp 94.3%, CUS: 3, LOE: III). (3). Circulating DNA-(a) IDH1R132H mutation detected in plasma by combined COLD and digital PCR (Sn: 60%, Sp: 100%, CUS: 3, LOE: III). 4. Exosomes-(a) SDC1 serum levels could discriminate GBM from LGG (Sn: 71%, Sp: 91%, CUS: 2C, LOE: VI). Our investigation showed that miRs appear to have the highest clinical utility. The LOE of the studies assessed is generally low. A combined approach between different biomarkers and traditional diagnostics may be considered. We identified four main classes of biomarkers produced by LGG. We examined each biomarker, classifying them by clinical utility score (CUS) and level of evidence (LOE). Micro-RNA (miRs) appears to have the highest CUS and LOE.

Robot-assisted spinal augmentation procedures: is it worth the increased effort?

PURPOSE: Spinal augmentation procedures (SAP) are standard procedures for vertebral compression fractures. Often, SAPs are carried out in a minimally invasive, percutaneous way. Certain anatomic conditions such as small pedicles or kyphotic deformities resulting from a significant collapse of the vertebral body might render the operation more difficult and increase the risk of complications. Thus, robot assistance might be useful to optimize the trajectory and to reduce procedure-associated complications. In this study robot-assisted percutaneous SAPs are compared with conventional fluoroscopy-guided percutaneous SAP. METHODS: A retrospective observational analysis was carried out. Standard demographic parameters were analyzed. Procedural data including radiation dosage records were screened. Biomechanical data were recorded. Cement volumes were analyzed. The precision of the pedicular trajectory was reviewed, and misplaced trajectories were categorized. Procedure-associated complications were analyzed and evaluated for their clinical significance. RESULTS: A total of 130 procedures were reviewed, and 94 patients were finally included. Osteoporotic fractures (OF) were the main indication (60.7%; OF 2-44%, OF 4-33%). Demographic parameters and clinically relevant complications were equally distributed between the two groups. Duration of surgery was significantly longer in robot-assisted procedures (p < 0.001). Intraoperative radiation exposure was equally distributed. Injected cement volume was similar in both groups. There was no significant difference in pedicle trajectory deviation. CONCLUSION: The use of robot assistance in SAP seems not to be superior with regard to accuracy, radiation exposure and the rate of complications when compared to fluoroscopy-guided SAP.

The Role of Diskectomy in Reducing Infectious Complications after Surgery for Lumbar Spondylodiscitis.

BACKGROUND: Surgery for pyogenic Spondylodiscitis as an adjunct to antibiotic therapy is an established treatment. However, the technique and extent of surgical debridement remains a matter of debate. Some propagate diskectomy in all cases. Others maintain that stand-alone instrumentation is sufficient. METHODS: We reviewed charts of patients who underwent instrumentation for pyogenic Spondylodiscitis with a minimum follow-up of 1 year. Patients were stratified according to whether they underwent diskectomy plus instrumentation or posterior instrumentation alone. Outcome measures included the need for surgical revision due to recurrent epidural intraspinal infection, wound revision, and construct failure. RESULTS: In all, 257 patients who underwent surgery for pyogenic Spondylodiscitis were identified. Diskectomy and interbody procedure (group A) was performed in 102 patients, while 155 patients underwent instrumentation surgery for Spondylodiscitis without intradiskal debridement (group B). The mean age was 67 ± 12 years, and 102 patients (39.7%) were females. No significant differences were found in the need for epidural abscess recurrence therapy (group A [2.0%] and 5 cases in group B [3%; p = 0.83]) and construct failure (p = 0.575). The need for wound revisions showed a tendency toward higher rates in the posterior instrumentation-only group, which failed to reach significance (p = 0.078). CONCLUSIONS: Overall, intraspinal relapse of surgically treated pyogenic diskitis was low in our retrospective series. The choice of surgical technique was not associated with a significant difference. However, a somewhat higher rate of wound infections requiring revision in the group where no diskectomy was performed has to be weighed against a longer duration of surgery in an already ill patient population.

Complications, Length of Hospital Stay, and Cost of Care after Surgery for Pyogenic Spondylodiscitis.

BACKGROUND: Infectious Spondylodiscitis is a heterogeneous disease usually affecting a fragile patient population with multiple comorbidities. Therefore, surgical and medical complications are important considerations before initiating treatment. METHODS: This retrospective analysis included data of 218 patients who underwent surgical treatment for pyogenic Spondylodiscitis between 2008 and 2016. Groups were divided into length of hospital stay (LOS) (group I ≤21 days and group II>21 days). Analysis included patient age, gender, Charlson comorbidity index, smoking, obesity, osteoporosis, colonization with multidrug-resistant bacteria, preoperative neurologic deficit, pre- and postoperative inflammation markers (CRP and WBC), duration of surgery, number of operated segments, vertebrectomy, and postoperative medical and surgical complications. The case value for each patient expressed in Euro was retrieved from hospital records and included in the analysis. RESULTS: Duration of stay after surgical treatment of Spondylodiscitis was ≤21 days (range: 4-21 days; mean: 16 days) in 41% of patients and >21 days (range: 22-162 days; mean: 41 days) in 59% of the patients. Multivariate analysis showed that both medical complications (odds ratio [OR]: 2.62; 95% confidence interval [CI]: 1.24-5.56; p=0.012) and surgical site infection (OR: 6.04; 95% CI: 2.35-15.51; p<0.001) were independently associated with a long hospital stay. Case values averaged at €21,667±1,579 (minimum: €2,888; maximum: €203,802) and correlated significantly with the length of hospital stay (Pearson's correlation coefficient: 0.681; p<0.05). The occurrence of a postoperative complication increased the cost of care significantly from €17,790 to 24,527 on average (p=0.025). CONCLUSIONS: This study provides benchmark data for patients treated surgically for Spondylodiscitis. Surgical site infection and medical complications are the main drivers of prolonged hospital stays and cost of care.

Postoperative Quality of Life in Patients with Pyogenic Spondylodiscitis.

BACKGROUND: Pyogenic spondylodiskitis affects a fragile patient population frequently fraught with severe comorbidities. Data on long-term outcomes, especially for patients undergoing surgery, are scarce. The aim of this study was to assess the long-term quality of life after surgical instrumentation. METHODS: Data of 218 patients who were treated for spondylodiskitis at our institution between January 2008 and July 2017 were reviewed. In-hospital death and mortality rates at 1 year and follow-up were assessed. A survey was conducted using the following questionnaires: Oswestry Disability Index (ODI), Short Form Work Ability Index (SF-WAI), 36-Item Short Form Health Survey (SF-36), and Short Form McGill Pain Questionnaire (SF-MPQ). We investigated the correlation between the assessed variables and clinical data including patient age, comorbidity score at admission, number of operated levels, corpectomy, and length of hospital stay. RESULTS: In-hospital mortality rate was 1.8% and 1-year mortality rate was 5.5%. At the final follow-up (mean 7 ± 6 years), the mortality rate was 45.4%. Seventy-four patients were lost to follow-up or refused to participate in the study. Forty-four patients responded to the survey and had a mean age of 73 years and mean follow-up of 7 ± 2 years. In the ODI questionnaire, disability grades were classified as minimal (23%), moderate (21%), severe (19%), complete (33%), and bed bound (4%). We found a significant correlation between inability to return to work and severe disability on ODI (p < 0.001), as well as a low score on any component of the SF-36 (p < 0.05). CONCLUSION: Despite low in-hospital and 1-year mortality rates, patients with surgically treated pyogenic spondylodiskitis are prone to long-term limitation in all domains of quality of life, especially in physical health and work ability.

Surgery for brain metastases: radiooncology scores predict survival-score index for radiosurgery, graded prognostic assessment, recursive partitioning analysis.

BACKGROUND: Radiooncological scores are used to stratify patients for radiation therapy. We assessed their ability to predict overall survival (OS) in patients undergoing surgery for metastatic brain disease. METHODS: We performed a post-hoc single-center analysis of 175 patients, prospectively enrolled in the MetastaSys study data. Score index of radiosurgery (SIR), graded prognostic assessment (GPA), and recursive partitioning analysis (RPA) were assessed. All scores consider age, systemic disease, and performance status prior to surgery. Furthermore, GPA and SIR include the number of intracranial lesions while SIR additionally requires metastatic lesion volume. Predictive values for case fatality at 1 year after surgery were compared among scoring systems. RESULTS: All scores produced accurate reflections on OS after surgery (p ≤ 0.003). Median survival was 21-24 weeks in patients scored in the unfavorable cohorts, respectively. In cohorts with favorable scores, median survival ranged from 42 to 60 weeks. Favorable SIR was associated with a hazard ratio (HR) of 0.44 [0.29, 0.66] for death within 1 year. For GPA, the HR amounted to 0.44 [0.25, 0.75], while RPA had a HR of 0.30 [0.14, 0.63]. Overall test performance was highest for the SIR. CONCLUSIONS: All scores proved useful in predicting OS. Considering our data, we recommend using the SIR for preoperative prognostic evaluation and counseling.

Nicotine Replacement Therapy for Smokers with Acute Aneurysmal Subarachnoid Hemorrhage: An International Survey.

INTRODUCTION: Smoking prevalence is twice as high among patients admitted to hospital because of the acute condition of aneurysmal subarachnoid hemorrhage (aSAH) as in the general population. Smoking cessation may improve the prognosis of aSAH, but nicotine replacement therapy (NRT) administered at the time of aSAH remains controversial because of potential adverse effects such as cerebral vasospasm. We investigated the international practice of NRT use for aSAH among neurosurgeons. METHODS: The online SurveyMonkey software was used to administer a 15-question, 5-min online questionnaire. An invitation link was sent to those 1425 of 1988 members of the European Association of Neurosurgical Societies (EANS) who agreed to participate in surveys to assess treatment strategies for withdrawal of tobacco smoking during aSAH. Factors contributing to physicians' posture towards NRT were assessed. RESULTS: A total of 158 physicians from 50 nations participated in the survey (response rate 11.1%); 68.4% (108) were affiliated with university hospitals and 67.7% (107) practiced at high-volume neurovascular centers with at least 30 treated aSAH cases per year. Overall, 55.7% (88) of physicians offered NRT to smokers with aSAH, 22.1% (35) offered non-NRT support including non-nicotine medication and counselling, while the remaining 22.1% (35) did not actively support smoking cessation. When smoking was not possible, 42.4% (67) of physicians expected better clinical outcomes when prescribing NRT instead of nicotine deprivation, 36.1% (57) were uncertain, 13.9% (22) assumed unaffected outcomes, and 7.6% (12) assumed worse outcomes. Only 22.8% (36) physicians had access to a local smoking cessation team in their practice, of whom half expected better outcomes with NRT as compared to deprivation. CONCLUSIONS: A small majority of the surveyed physicians of the EANS offered NRT to support smoking cessation in hospitalized patients with aSAH. However, less than half believed that NRT could positively impact clinical outcome as compared to deprivation. This survey demonstrated the lack of consensus regarding use of NRT for hospitalized smokers with aSAH.

Endoscope-assisted visualization of 5-aminolevulinic acid fluorescence in surgery for brain metastases.

OBJECTIVE: Fluorescence-guided resection of cerebral metastases has been proposed as an approach to visualize residual tumor tissue and maximize the extent of resection. Critics have argued that tumor cells at the resection margins might be overlooked under microscopic visualization because of technical limitations. Therefore, an endoscope, which is capable of inducing fluorescence, has been applied with the aim of improving exposure of fluorescent tumor tissue. In this retrospective analysis, authors assessed the utility of endoscope assistance in 5-aminolevulinic acid (5-ALA) fluorescence-guided resection of brain metastases. METHODS: Between June 2013 and December 2016, a standard 20-mg/kg dose of 5-ALA was administered 4 hours prior to surgery in 26 patients with suspected single brain metastases. After standard neuronavigated microsurgical tumor resection, a microscope capable of inducing fluorescence was used to examine tumor margins. The authors classified the remaining fluorescence into 3 grades (0 = none, 1 = weak, and 2 = strong). Endoscopic assistance was employed if no or only weak fluorescence was visualized at the resection margins under the microscope. Endoscopically identified fluorescent tissue at the margins was resected and evaluated separately via histological examination to prove or disprove tumor infiltration. RESULTS: Under the microscope, weakly fluorescent tissue was seen at the margins of the resection cavity in 15/26 (57.7%) patients. In contrast, endoscopic inspection revealed strongly fluorescent tissue in 22/26 (84.6%) metastases. In 11/26 (42.3%) metastases no fluorescence at the tumor margins was detected by the microscope; however, strong fluorescence was visualized under the endoscope in 7 (63.6%) of these 11 metastases. In the 15 metastases with microscopically weak fluorescence, strong fluorescence was seen when using the endoscope. Neither microscopic nor endoscopic fluorescence was found in 4/26 (15.4%) cases. In the 26 patients, 96 histological specimens were obtained from the margins of the resection cavity. Findings from these specimens were in conjunction with the histopathological findings, allowing identification of metastatic infiltration with a sensitivity of 95.5% and a specificity of 75% using endoscope assistance. CONCLUSIONS: Fluorescence-guided endoscope assistance may overcome the technical limitations of the conventional microscopic exposure of 5-ALA-fluorescent metastases and thereby increase visualization of fluorescent tumor tissue at the margins of the resection cavity with high sensitivity and acceptable specificity.

WNT11/ROR2 signaling is associated with tumor invasion and poor survival in breast cancer.

BACKGROUND: Breast cancer has been associated with activation of the WNT signaling pathway, although no driver mutations in WNT genes have been found yet. Instead, a high expression of the alternative WNT receptor ROR2 was observed, in particular in breast cancer brain metastases. However, its respective ligand and downstream signaling in this context remained unknown. METHODS: We modulated the expression of ROR2 in human breast cancer cells and characterized their gene and protein expression by RNA-Seq, qRT-PCR, immunoblots and reverse phase protein array (RPPA) combined with network analyses to understand the molecular basis of ROR2 signaling in breast cancer. Using co-immunoprecipitations, we verified the interaction of ROR2 with the identified ligand, WNT11. The functional consequences of WNT11/ROR2 signaling for tumor cell aggressiveness were assessed by microscopy, impedance sensing as well as viability and invasion assays. To evaluate the translational significance of our findings, we performed gene set enrichment, expression and survival analyses on human breast cancer brain metastases. RESULTS: We found ROR2 to be highly expressed in aggressive breast tumors and associated with worse metastasis-free survival. ROR2 overexpression induced a BRCAness-like phenotype in a cell-context specific manner and rendered cells resistant to PARP inhibition. High levels of ROR2 were furthermore associated with defects in cell morphology and cell-cell-contacts leading to increased tumor invasiveness. On a molecular level, ROR2 overexpression upregulated several non-canonical WNT ligands, in particular WNT11. Co-immunoprecipitation confirmed that WNT11 indeed interacts with the cysteine-rich domain of ROR2 and triggers its invasion-promoting signaling via RHO/ROCK. Knockdown of WNT11 reversed the pro-invasive phenotype and the cellular changes in ROR2-overexpressing cells. CONCLUSIONS: Taken together, our study revealed a novel auto-stimulatory loop in which ROR2 triggers the expression of its own ligand, WNT11, resulting in enhanced tumor invasion associated with breast cancer metastasis.

Safety aspects of opioid-naïve patients with high-grade glioma treated with D,L-Methadone: an observational case series.

It was suggested that D, L-Methadone might improve the clinical course of glioma patients. Owing to massive press coverage, patients demand the prescription of D, L-Methadone, but regarding its adjunctive use in glioma therapy there is no standard medication plan. Furthermore, it is not known which side effects the administration of D, L-Methadone might harbor, especially if the patients are opioid-naïve and if D, L-Methadone therapy was managed by the patients themselves or their general practitioners. Opioid-naïve patients with high-grade glioma (new diagnosis or recurrent) receiving D, L-Methadone were included in this retrospective observational analysis. Side effects were assigned if the condition deteriorated in conjunction with the initiation of D, L-Methadone and resolved/ ameliorated after cessation of the intake/reduction of the dosage. Side effects were categorized according to the common toxicity criteria (CTC). Twenty-four patients were included. All patients were opioid-naïve and received D, L-Methadone from their general practitioners. Sixteen patients experienced side effects. The median dosage when side effects began to occur was 15.8 mg/ 24 h. Fatigue and mood changes were reported most frequently (14 of 24 patients). Five patients had severe side effects related to relatively high doses. In all cases, symptoms resolved after cessation or dose reduction. Our results show that D/L M intake lead to frequent occurrence of side effects in opioid-naïve patients especially when not handled with caution and close supervision. Patients, their relatives, their GPs and neuro-oncologists need to be informed about the broad spectrum of side effects in order to thoroughly counsel glioma patients.

The association of patient age with postoperative morbidity and mortality following resection of intracranial tumors.

Introduction: The postoperative functional status of patients with intracranial tumors is influenced by patient-specific factors, including age. Research question: This study aimed to elucidate the association between age and postoperative morbidity or mortality following the resection of brain tumors. Material and methods: A multicenter database was retrospectively reviewed. Functional status was assessed before and 3-6 months after tumor resection by the Karnofsky Performance Scale (KPS). Uni- and multivariable linear regression were used to estimate the association of age with postoperative change in KPS. Logistic regression models for a ≥10-point decline in KPS or mortality were built for patients ≥75 years. Results: The total sample of 4864 patients had a mean age of 56.4 â€‹± â€‹14.4 years. The mean change in pre-to postoperative KPS was -1.43. For each 1-year increase in patient age, the adjusted change in postoperative KPS was -0.11 (95% CI -0.14 - - 0.07). In multivariable analysis, patients ≥75 years had an odds ratio of 1.51 to experience postoperative functional decline (95%CI 1.21-1.88) and an odds ratio of 2.04 to die (95%CI 1.33-3.13), compared to younger patients. Discussion: Patients with intracranial tumors treated surgically showed a minor decline in their postoperative functional status. Age was associated with this decline in function, but only to a small extent. Conclusion: Patients ≥75 years were more likely to experience a clinically meaningful decline in function and about two times as likely to die within the first 6 months after surgery, compared to younger patients.

Development of a Complication- and Treatment-Aware Prediction Model for Favorable Functional Outcome in Aneurysmal Subarachnoid Hemorrhage Based on Machine Learning.

BACKGROUND: Current prognostic tools in aneurysmal subarachnoid hemorrhage (aSAH) are constrained by being primarily based on patient and disease characteristics on admission. OBJECTIVE: To develop and validate a complication- and treatment-aware outcome prediction tool in aSAH. METHODS: This cohort study included data from an ongoing prospective nationwide multicenter registry on all aSAH patients in Switzerland (Swiss SOS [Swiss Study on aSAH]; 2009-2015). We trained supervised machine learning algorithms to predict a binary outcome at discharge (modified Rankin scale [mRS] ≤ 3: favorable; mRS 4-6: unfavorable). Clinical and radiological variables on admission ("Early" Model) as well as additional variables regarding secondary complications and disease management ("Late" Model) were used. Performance of both models was assessed by classification performance metrics on an out-of-sample test dataset. RESULTS: Favorable functional outcome at discharge was observed in 1156 (62.0%) of 1866 patients. Both models scored a high accuracy of 75% to 76% on the test set. The "Late" outcome model outperformed the "Early" model with an area under the receiver operator characteristics curve (AUC) of 0.85 vs 0.79, corresponding to a specificity of 0.81 vs 0.70 and a sensitivity of 0.71 vs 0.79, respectively. CONCLUSION: Both machine learning models show good discrimination and calibration confirmed on application to an internal test dataset of patients with a wide range of disease severity treated in different institutions within a nationwide registry. Our study indicates that the inclusion of variables reflecting the clinical course of the patient may lead to outcome predictions with superior predictive power compared to a model based on admission data only.

Incidence and Outcome of Aneurysmal Subarachnoid Hemorrhage: The Swiss Study on Subarachnoid Hemorrhage (Swiss SOS).

BACKGROUND AND PURPOSE: The purpose of this study was to assess nationwide incidence and outcomes of aneurysmal subarachnoid hemorrhage (aSAH). The Swiss SOS (Swiss Study on Subarachnoid Hemorrhage) was established in 2008 and offers the unique opportunity to provide this data from the point of care on a nationwide level. METHODS: All patients with confirmed aneurysmal subarachnoid hemorrhage admitted between January 1, 2009 and December 31, 2014, within Switzerland were recorded in a prospective registry. Incidence rates were calculated based on time-matched population data. Admission parameters and outcomes at discharge and at 1 year were recorded. RESULTS: We recorded data of 1787 consecutive patients. The incidence of aneurysmal subarachnoid hemorrhage in Switzerland was 3.7 per 100 000 persons/y. The number of female patients was 1170 (65.5%). With a follow-up rate of 91.3% at 1 year, 1042 patients (58.8%) led an independent life according to the modified Rankin Scale (0-2). About 1 in 10 patients survived in a dependent state (modified Rankin Scale, 3-5; n=185; 10.4%). Case fatality was 20.1% (n=356) at discharge and 22.1% (n=391) after 1 year. CONCLUSIONS: The current incidence of aneurysmal subarachnoid hemorrhage in Switzerland is lower than expected and an indication of a global trend toward decreasing admissions for ruptured intracranial aneurysms. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT03245866.

Do we underdiagnose osteoporosis in patients with pyogenic spondylodiscitis?

OBJECTIVE: Pyogenic spondylodiscitis affects a fragile patient population. Surgical treatment in cases of instability entails instrumentation, and loosening of this instrumentation is a frequent occurrence in pyogenic spondylodiscitis. The authors therefore attempted to investigate whether low bone mineral density (BMD)-which is compatible with the diagnosis of osteoporosis-is underdiagnosed in patients with pyogenic spondylodiscitis. How osteoporosis was treated and how it affected implant stability were further analyzed. METHODS: Charts of patients who underwent operations for pyogenic spondylodiscitis were retrospectively reviewed for clinical data, prior medical history of osteoporosis, and preoperative CT scans of the thoracolumbar spine. In accordance with a previously validated high-fidelity opportunistic CT assessment, average Hounsfield units (HUs) in vertebral bodies of L1 and L4 were measured. Based on the validation study, the authors opted for a conservative cutoff value for low BMD, being compatible with osteoporosis ≤ 110 HUs. Baseline and outcome variables, including implant failure and osteoporosis interventions, were entered into a multivariate logistic model for statistical analysis. RESULTS: Of 200 consecutive patients who underwent fusion surgery for pyogenic spondylodiscitis, 64% (n = 127) were male and 66% (n = 132) were older than 65 years. Seven percent (n = 14) had previously been diagnosed with osteoporosis. The attenuation analysis revealed HU values compatible with osteoporosis in 48% (95/200). The need for subsequent revision surgery due to implant failure showed a trend toward an association with estimated low BMD (OR 2.11, 95% CI 0.95-4.68, p = 0.067). Estimated low BMD was associated with subsequent implant loosening (p < 0.001). Only 5% of the patients with estimated low BMD received a diagnosis and pharmacological treatment of osteoporosis within 1 year after spinal instrumentation. CONCLUSIONS: Relying on past medical history of osteoporosis is insufficient in the management of patients with pyogenic spondylodiscitis. This is the first study to identify a substantially missed opportunity to detect osteoporosis and to start pharmacological treatment after surgery for prevention of implant failure. The authors advocate for routine opportunistic CT evaluation for a better estimation of bone quality to initiate diagnosis and treatment for osteoporosis in these patients.

Survival after resection of brain metastases with white light microscopy versus fluorescence-guidance: A matched cohort analysis of the Metastasys study data.

BACKGROUND: Metastatic brain disease continues to have a dismal prognosis. Previous studies achieved a reduction of local recurrence rates by aggressively resecting the peritumoral zone (supramarginal resection) or using 5-aminolaevulinic acid (5-ALA) fluorescence. The aim of the present study is to assess whether the use of 5-ALA has an impact on local recurrence or survival compared to conventional white light microscopic tumor resection. MATERIALS AND METHODS: We included consecutive patients who underwent surgical resection of brain metastases. Two groups were compared: In the "white light" group, resection was performed with conventional microscopy. In the 5-ALA group, fluorescence guided peritumoral resection was additionally performed after standard microscopic resection. In-brain recurrence and mortality were compared between groups. RESULTS: N = 175 patients were included in the study. All baseline parameters were similarly distributed with no significant difference between surgical groups. Local in-brain recurrence occurred in 21/175 patients (12%) with a rate of 15/119 (12.6%) in the white light and 6/56 (10.7%) in the 5-ALA group (p = 0.720). The use of 5-ALA influenced neither in-brain recurrence (OR 0.59 [CI = 95% 0.18; 1.99], p = 0.40) nor mortality (OR 0.71 [CI = 95% 0.27; 1.85], p = 0.49). CONCLUSIONS: The use of 5-ALA did not result in lower in-brain recurrence or mortality compared to the use of white light microscopy. The most prominent predictors of survival remain favorable preoperative performance status, a low tumor diameter and the absence of multiple cerebral lesions.

Development and external validation of a clinical prediction model for functional impairment after intracranial tumor surgery.

OBJECTIVE: Decision-making for intracranial tumor surgery requires balancing the oncological benefit against the risk for resection-related impairment. Risk estimates are commonly based on subjective experience and generalized numbers from the literature, but even experienced surgeons overestimate functional outcome after surgery. Today, there is no reliable and objective way to preoperatively predict an individual patient's risk of experiencing any functional impairment. METHODS: The authors developed a prediction model for functional impairment at 3 to 6 months after microsurgical resection, defined as a decrease in Karnofsky Performance Status of ≥ 10 points. Two prospective registries in Switzerland and Italy were used for development. External validation was performed in 7 cohorts from Sweden, Norway, Germany, Austria, and the Netherlands. Age, sex, prior surgery, tumor histology and maximum diameter, expected major brain vessel or cranial nerve manipulation, resection in eloquent areas and the posterior fossa, and surgical approach were recorded. Discrimination and calibration metrics were evaluated. RESULTS: In the development (2437 patients, 48.2% male; mean age ± SD: 55 ± 15 years) and external validation (2427 patients, 42.4% male; mean age ± SD: 58 ± 13 years) cohorts, functional impairment rates were 21.5% and 28.5%, respectively. In the development cohort, area under the curve (AUC) values of 0.72 (95% CI 0.69-0.74) were observed. In the pooled external validation cohort, the AUC was 0.72 (95% CI 0.69-0.74), confirming generalizability. Calibration plots indicated fair calibration in both cohorts. The tool has been incorporated into a web-based application available at https://neurosurgery.shinyapps.io/impairment/. CONCLUSIONS: Functional impairment after intracranial tumor surgery remains extraordinarily difficult to predict, although machine learning can help quantify risk. This externally validated prediction tool can serve as the basis for case-by-case discussions and risk-to-benefit estimation of surgical treatment in the individual patient.