Minimally invasive surgical evacuation for spontaneous cerebellar hemorrhage: a case series and systematic review.

Spontaneous cerebellar hemorrhage (scICH) is a subset of intracerebral hemorrhage accounting for 5-10% of all cases. Despite potential advantages, minimally invasive surgical evacuation of scICH may be an underutilized strategy when compared to unilateral or bilateral large suboccipital craniectomy or craniotomy, with or without duraplasty. We performed a retrospective single-center cohort study and a systematic literature review. Radiographic and clinical data were recorded and analyzed. Five consecutive patients with minimally invasive surgical evacuation of scICH were identified. Average hematoma size was 16.4 ± 3.0 cm3. Mean Glasgow coma score (GCS) prior to surgery was 11.6 ± 3.0 with improvement to 14.6 ± 0.4 postoperatively. Mean hematoma evacuation was 92.6 ± 0.6% as confirmed by postoperative computed tomography (CT) imaging. All patients achieved a modified Rankin Scale (mRS) score of 0 or 1 with an average follow-up time of 31 ± 22 months. Mean length of hospital stay was 8.8 ± 3.0 days. No patients experienced significant complications or required reoperation. Systematic review revealed similar results for minimally invasive evacuation of scICH when reporting disaggregated outcomes. A review of recent studies utilizing large unilateral or bilateral suboccipital craniectomy or craniotomy, with or without duraplasty, revealed higher morbidity and mortality rates than minimally invasive surgical evacuation of scICH. Minimally invasive evacuation of scICH is safe and effective. Near complete evacuation of hematoma can be achieved with lower morbidity and mortality than large suboccipital craniectomy or craniotomy. A multi-center, prospective, and rigorous trial comparing the two strategies for evacuation of scICH is warranted.

Acute kidney injury after cardiac surgery: A comparison of different definitions.

AIM: Acute kidney injury (AKI) after cardiac surgery increases morbidity and mortality. Different definitions for AKI have been used such as Acute Kidney Injury Network (AKIN), Kidney Disease: Improving Global Outcomes (KDIGO) or risk, injury, failure, loss, end-stage kidney disease (RIFLE). The aim of this study is to determine the best definition of AKI after cardiac surgery with the largest impact on the outcome. METHODS: This retrospective study of cardiac surgery patients compared the incidence and effect on outcome (90-day and 1-year mortality) of different definitions of AKI: RIFLE, AKIN and KDIGO. Additionally, we defined transient AKI (increase in serum creatinine that resolved in <72 hours), sustained (increase in serum creatinine within 48 hours that remained for >72 hours), and late (increase in serum creatinine after 48 hours). RESULTS: Of the included 1551 patients, 410 patients developed AKI defined by AKIN criteria, 449 defined by KDIGO and 217 defined by RIFLE-Risk criteria. Hundred and nine patients developed transient AKI (6.9%), 183 patients had sustained AKI (11.6%), and 106 patients had late AKI (6.7%). The best definition with the highest positive likelihood ratio was RIFLE-Risk (positive likelihood ratio = 2.32) followed by "sustained AKI" (positive likelihood ratio = 2.27). AKI defined by AKIN criteria missed all 80 patients with late AKI and 39 patients with KDIGO AKI. CONCLUSION: Risk, injury, failure, loss, end-stage kidney disease-risk was the best definition of AKI as determined by the ability to predict short-term mortality. A substantial number of patients developed AKI only after 48 hours, and these were missed when using AKIN criteria. AKIN criteria are not sensitive enough to capture all episodes of AKI in this population.

Functional Coagulation Differences Between Lobar and Deep Intracerebral Hemorrhage Detected by Rotational Thromboelastometry: A Pilot Study.

BACKGROUND: Lobar intracerebral hemorrhage (ICH) is known to have better clinical outcomes and preliminary evidence of less hematoma expansion compared to deep ICH. No functional coagulation differences between lobar and deep ICH have been identified using traditional plasma-based coagulation tests. We investigated for coagulation differences between lobar and deep ICH using whole-blood coagulation testing (Rotational Thromboelastometry: [ROTEM]). METHODS: Clinical, radiographic, and laboratory data were prospectively collected for primary ICH patients enrolled in a single-center ICH study. Patients with preceding anticoagulant use or admission coagulopathy on traditional laboratory testing were excluded. Lobar and deep ICH patients receiving admission ROTEM were analyzed. Linear regression was used to assess the association of ICH location with coagulation test results after adjusting for potential confounders. RESULTS: There were 12 lobar and 19 deep ICH patients meeting inclusion criteria. Lobar ICH patients were significantly older and predominantly female. Lobar ICH had faster intrinsic pathway coagulation times (139.8 vs 203.2 s; 95% CI - 179.91 to - 45.96; p = 0.002) on ROTEM testing compared to deep ICH after adjusting for age, sex, and hematoma volume. This revealed functional coagulation differences, specifically quicker clot formation in lobar compared to deep ICH. No differences were noted using traditional coagulation testing (prothrombin time/partial thromboplastin time/platelet count). CONCLUSIONS: Our pilot data may suggest that there are functional coagulation differences between lobar and deep ICH identified using ROTEM. Whole-blood coagulation testing may be useful in assessing coagulopathy in ICH patients and in determining reversal treatment paradigms, though further work is needed.

Biomarkers of immunotherapy in glioblastoma.

Glioblastoma (GBM) is the most common primary brain cancer, comprising half of all malignant brain tumors. Patients with GBM have a poor prognosis, with a median survival of 14-15 months. Current therapies for GBM, including chemotherapy, radiotherapy, and surgical resection, remain inadequate. Novel therapies are required to extend patient survival. Although immunotherapy has shown promise in other cancers, including melanoma and non-small lung cancer, its efficacy in GBM has been limited to subsets of patients. Identifying biomarkers of immunotherapy response in GBM could help stratify patients, identify new therapeutic targets, and develop more effective treatments. This article reviews existing and emerging biomarkers of clinical response to immunotherapy in GBM. The scope of this review includes immune checkpoint inhibitor and antitumoral vaccination approaches, summarizing the variety of molecular, cellular, and computational methodologies that have been explored in the setting of anti-GBM immunotherapies.

Barriers to neurosurgery for medical students: a national study focused on the intersectionality of gender and race.

OBJECTIVE: Despite 51.2% of medical school graduates being female, only 29.8% of neurosurgery residency applicants are female. Furthermore, only 12.6% of neurosurgery applicants identify as underrepresented in medicine (URM). Evaluating the entry barriers for female and URM students is crucial in promoting the equity and diversity of the neurosurgical workforce. The objective of this study was to evaluate barriers to neurosurgery for medical students while considering the interaction between gender and race. METHODS: A Qualtrics survey was distributed widely to US medical students, assessing 14 factors of hesitancy toward neurosurgery. Likert scale responses, representing statement agreeability, converted to numeric values on a 7-point scale were analyzed by Mann-Whitney U-test and ANOVA comparisons with Bonferroni correction. RESULTS: Of 540 respondents, 68.7% were female and 22.6% were URM. There were 22.6% male non-URM, 7.4% male URM, 53.5% female non-URM, and 15.2% female URM respondents. The predominant reasons for hesitancy toward neurosurgery included work/life integration, length of training, competitiveness of residency position, and perceived malignancy of the field. Females were more hesitant toward neurosurgery due to maternity/paternity needs (p = 0.005), the absence of seeing people like them in the field (p < 0.001), and opportunities to pursue health equity work (p < 0.001). Females were more likely to have difficulties finding a mentor in neurosurgery who represented their identities (p = 0.017). URM students were more hesitant toward neurosurgery due to not seeing people like them in the field (p < 0.001). Subanalysis revealed that when students were stratified by both gender and URM status, there were more reasons for hesitancy toward neurosurgery that had significant differences between groups (male URM, male non-URM, female URM, and female non-URM students), suggesting the importance of intersectionality in this analysis. CONCLUSIONS: The authors highlight the implications of gender and racial diversity in the neurosurgical workforce on medical student interest and recruitment. Their findings suggest the importance of actively working to address these barriers, including 1) maternity/paternity policy reevaluation, standardization, and dissemination; and 2) actively providing resources for the creation of mentorship relationships for both women and URM students in an effort to create a workforce that aligns with the changing demographics of medical graduates to continue to improve diversity in neurosurgery.

Hypercoagulable viscoelastic blood clot characteristics in critically ill coronavirus disease 2019 patients and associations with thrombotic complications.

BACKGROUND: Critically ill coronavirus disease 2019 (COVID-19) patients have frequent thrombotic complications and laboratory evidence of hypercoagulability. The relationship of coagulation tests and thrombosis requires investigation to identify best diagnostic and treatment approaches. We assessed for hypercoagulable characteristics in critically ill COVID-19 patients using rotational thromboelastometry (ROTEM) and explored relationships of D-dimer and ROTEM measurements with thrombotic complications. METHODS: Critically ill adult COVID-19 patients receiving ROTEM testing between March and April 2020 were analyzed. Patients receiving therapeutic anticoagulation before ROTEM were excluded. Rotational thromboelastometry measurements from COVID-19 patients were compared with non-COVID-19 patients matched by age, sex, and body mass index. Intergroup differences in ROTEM measurements were assessed using t tests. Correlations of D-dimer levels to ROTEM measurements were assessed in COVID-19 patients who had available concurrent testing. Intergroup differences of D-dimer and ROTEM measurements were explored in COVID-19 patients with and without thrombosis. RESULTS: Of 30 COVID-19 patients receiving ROTEM, we identified hypercoagulability from elevated fibrinogen compared with non-COVID-19 patients (fibrinogen assay maximum clot firmness [MCF], 47 ± 13 mm vs. 20 ± 7 mm; mean intergroup difference, 27.4 mm; 95% confidence interval [CI], 22.1-32.7 mm; p < 0.0001). In our COVID-19 cohort, thrombotic complications were identified in 33%. In COVID-19 patients developing thrombotic complications, we identified higher D-dimer levels (17.5 ± 4.3 µg/mL vs. 8.0 ± 6.3 µg/mL; mean difference, 9.5 µg/mL; 95% CI, 13.9-5.1; p < 0.0001) but lower fibrinogen assay MCF (39.7 ± 10.8 mm vs. 50.1 ± 12.0 mm; mean difference, -11.2 mm; 95% CI, -2.1 to -20.2; p = 0.02) compared with patients without thrombosis. We identified negative correlations of D-dimer levels and ROTEM MCF in these patients (r = -0.61; p = 0.001). CONCLUSION: We identified elevated D-dimer levels and hypercoagulable blood clot characteristics from increased fibrinogen on ROTEM testing in critically ill COVID-19 patients. However, we identified lower, albeit still hypercoagulable, ROTEM measurements of fibrinogen in COVID-19 patients with thrombotic complications compared with those without. Further work is required to externally validate these findings and to investigate the mechanistic drivers for these relationships to identify best diagnostic and treatment approaches for these patients. LEVEL OF EVIDENCE: Epidemiologic, level IV.

Mortality and renal outcomes of patients with severe COVID-19 treated in a provisional intensive care unit.

COVID-19 has created an enormous health crisis and this spring New York City had a severe outbreak that pushed health and critical care resources to the limit. A lack of adequate space for mechanically ventilated patients induced our hospital to convert operating rooms into critical care areas (OR-ICU). A large number of COVID-19 will develop acute kidney injury that requires renal replacement therapy (RRT). We included 116 patients with COVID-19 who required mechanical ventilation and were cared for in our OR-ICU. At 90 days and at discharge 35 patients died (30.2%). RRT was required by 45 of the 116 patients (38.8%) and 18 of these 45 patients (40%) compared to 17 with no RRT (23.9%, ns) died during hospitalization and after 90 days. Only two of the 27 patients who required RRT and survived required RRT at discharge and 90 days. When defining renal recovery as a discharge serum creatinine within 150% of baseline, 68 of 78 survivors showed renal recovery (87.2%). Survival was similar to previous reports of patients with severe COVID-19 for patients cared for in provisional ICUs compared to standard ICUs. Most patients with severe COVID-19 and AKI are likely to recover full renal function.

Predicting Poor Outcome of COVID-19 Patients on the Day of Admission with the COVID-19 Score.

BACKGROUND: COVID-19 may result in multiorgan failure and death. Early detection of patients at risk may allow triage and more intense monitoring. The aim of this study was to develop a simple, objective admission score, based on laboratory tests, that identifies patients who are likely going to deteriorate. METHODS: This is a retrospective cohort study of all COVID-19 patients admitted to a tertiary academic medical center in New York City during the COVID-19 crisis in spring 2020. The primary combined endpoint included intubation, stage 3 acute kidney injury (AKI), or death. Laboratory tests available on admission in at least 70% of patients (and age) were included for univariate analysis. Tests that were statistically or clinically significant were then included in a multivariate binary logistic regression model using stepwise exclusion. 70% of all patients were used to train the model, and 30% were used as an internal validation cohort. The aim of this study was to develop and validate a model for COVID-19 severity based on biomarkers. RESULTS: Out of 2545 patients, 833 (32.7%) experienced the primary endpoint. 53 laboratory tests were analyzed, and of these, 47 tests (and age) were significantly different between patients with and without the endpoint. The final multivariate model included age, albumin, creatinine, C-reactive protein, and lactate dehydrogenase. The area under the ROC curve was 0.850 (CI [95%]: 0.813, 0.889), with a sensitivity of 0.800 and specificity of 0.761. The probability of experiencing the primary endpoint can be calculated as p=e (-2.4475+0.02492age - 0.6503albumin+0.81926creat+0.00388CRP+0.00143LDH)/1+e (-2.4475+ 0.02492age - 0.6503albumin+0.81926creat+0.00388CRP+0.00143LDH). CONCLUSIONS: Our study demonstrated that poor outcome in COVID-19 patients can be predicted with good sensitivity and specificity using a few laboratory tests. This is useful for identifying patients at risk during admission.

Focused ultrasound mediated blood-brain barrier opening is safe and feasible in a murine pontine glioma model.

Drug delivery in diffuse intrinsic pontine glioma is significantly limited by the blood-brain barrier (BBB). Focused ultrasound (FUS), when combined with the administration of microbubbles can effectively open the BBB permitting the entry of drugs across the cerebrovasculature into the brainstem. Given that the utility of FUS in brainstem malignancies remains unknown, the purpose of our study was to determine the safety and feasibility of this technique in a murine pontine glioma model. A syngeneic orthotopic model was developed by stereotactic injection of PDGF-B+PTEN-/-p53-/- murine glioma cells into the pons of B6 mice. A single-element, spherical-segment 1.5 MHz ultrasound transducer driven by a function generator through a power amplifier was used with concurrent intravenous microbubble injection for tumor sonication. Mice were randomly assigned to control, FUS and double-FUS groups. Pulse and respiratory rates were continuously monitored during treatment. BBB opening was confirmed with gadolinium-enhanced MRI and Evans blue. Kondziela inverted screen testing and sequential weight lifting measured motor function before and after sonication. A subset of animals were treated with etoposide following ultrasound. Mice were either sacrificed for tissue analysis or serially monitored for survival with daily weights. FUS successfully caused BBB opening while preserving normal cardiorespiratory and motor function. Furthermore, the degree of intra-tumoral hemorrhage and inflammation on H&E in control and treated mice was similar. There was also no difference in weight loss and survival between the groups (p > 0.05). Lastly, FUS increased intra-tumoral etoposide concentration by more than fivefold. FUS is a safe and feasible technique for repeated BBB opening and etoposide delivery in a preclinical pontine glioma model.

Complete Microsurgical Resection of Large Retrochiasmatic Hypothalamic Craniopharyngioma by Transpetrosal Approach: 2-Dimensional Operative Video.

This two-dimensional video shows the technical nuances of complete microsurgical resection of a hypothalamic craniopharyngioma located in the retrochiasmatic region by the transpetrosal approach. This 49-yr-old man presented with progressive fatigue, excessive sleepiness, and difficulty in vision in both eyes. He was found to have right CN 3 paralysis and bitemporal hemianopsia on neurological examination. Further workup revealed panhypopituitarism. Brain magnetic resonance imaging (MRI) demonstrated a large solid retrochiasmatic hypothalamic lesion with homogeneous contrast enhancement, measuring 2.1 × 2.6 × 2.4 cm. Optic chiasm was prefixed, and the tumor was just posterior to the pituitary stalk area. The preoperative differential diagnosis included hypothalamic astrocytoma, craniopharyngioma, germinoma, and histiocytosis. Because of the prefixed chiasm, a presigmoid, transpetrosal approach was performed. Our initial plan was a large biopsy, but based on frozen section histology, we decided to excise the tumor completely. The tumor had a pseudocapsule, which was firm and yellowish. It was debulked, dissected from the surrounding hypothalamus, and removed completely. The pituitary stalk was found at the anterior and inferior ends of the tumor and was preserved. Postoperatively, the patient developed diabetes insipidus and requires desmopressin replacement, which was gradually tapered. For panhypopituitarism, he is receiving thyroxine, hydrocortisone, and testosterone. Postoperatively, patient had an improvement in vision in his left eye and ptosis was improving in the right eye with mRs 1- at 10-wk follow-up. An informed consent was obtained from the patient prior to the surgery, which included videotaping of the procedure and its distribution for educational purposes. All relevant patient identifiers have also been removed from the video and accompanying radiology slides.

A phase II randomized controlled trial of tiopronin for aneurysmal subarachnoid hemorrhage.

OBJECTIVE: Delayed cerebral ischemia (DCI) is a significant contributor to poor outcomes after aneurysmal subarachnoid hemorrhage (aSAH). The neurotoxin 3-aminopropanal (3-AP) is upregulated in cerebral ischemia. This phase II clinical trial evaluated the efficacy of tiopronin in reducing CSF 3-AP levels in patients with aSAH. METHODS: In this prospective, randomized, double-blind, placebo-controlled, multicenter clinical trial, 60 patients were assigned to receive tiopronin or placebo in a 1:1 ratio. Treatment was commenced within 96 hours after aSAH onset, administered at a dose of 3 g daily, and continued until 14 days after aSAH or hospital discharge, whichever occurred earlier. The primary efficacy outcome was the CSF 3-AP level at 7 ± 1 days after aSAH. RESULTS: Of the 60 enrolled patients, 29 (97%) and 27 (93%) in the tiopronin and placebo arms, respectively, received more than one dose of the study drug or placebo. At post-aSAH day 7 ± 1, CSF samples were available in 41% (n = 12/29) and 48% (n = 13/27) of patients in the tiopronin and placebo arms, respectively. No difference in CSF 3-AP levels at post-aSAH day 7 ± 1 was observed between the study arms (11 ± 12 nmol/mL vs 13 ± 18 nmol/mL; p = 0.766). Prespecified adverse events led to early treatment cessation for 4 patients in the tiopronin arm and 2 in the placebo arm. CONCLUSIONS: The power of this study was affected by missing data. Therefore, the authors could not establish or refute an effect of tiopronin on CSF 3-AP levels. Additional observational studies investigating the role of 3-AP as a biomarker for DCI may be warranted prior to its use as a molecular target in future clinical trials.Clinical trial registration no.: NCT01095731 (ClinicalTrials.gov).