abbreviatioNs AUC = area under the curve; BBB = blood-brain barrier; DAI = diffuse axonal injury; Eg = estrogen; FIM = functional independence measure; GCS = Glasgow Coma Scale; GFAP = glial fibrillary acidic protein; GOS = Glasgow Outcome Scale; ICP = intracranial pressure; IL = interleukin; IQR = interquartile range; NGF = nerve growth factor; NSE = neuron-specific enolase; Pg = progesterone; ROC = receiver operating characteristic; sTBI = severe traumatic brain injury; TNF-a = tumor necrosis factor-a. Pg]). This analysis was performed using the sandwich enzyme-linked immunosorbent assay technique at admission and 7 days later for 86 patients, irrespective of assigned group. The long-term predictive values of serum biomarkers for dichotomized Glasgow Outcome Scale (GOS) score, functional independence measure, and survival status at 6 and 12 months were analyzed using an adjusted binary logistic regression model and receiver operating characteristic curve. results A favorable GOS score (4-5) at 1 year was predicted by higher admission IL-6 (above 108.36 pg/ml; area under the curve [AUC] 0.69, sensitivity 52%, and specificity 78.6%) and Day 7 Pg levels (above 3.15 ng/ml; AUC 0.79, sensitivity 70%, and specificity 92.9%). An unfavorable GOS score (1-3) at 1 year was predicted by higher Day 7 GFAP levels (above 9.50 ng/ml; AUC 0.82, sensitivity 78.6%, and specificity 82.4%). Survivors at 1 year had significantly higher Day 7 Pg levels (above 3.15 ng/ml; AUC 0.78, sensitivity 66.7%, and specificity 90.9%). Nonsurvivors at 1 year had significantly higher Day 7 GFAP serum levels (above 11.14 ng/ml; AUC 0.81, sensitivity 81.8%, and specificity 88.9%) and Day 7 IL-6 serum levels (above 71.26 pg/ml; AUC 0.87, sensitivity 81.8%, and specificity 87%). In multivariate logistic regression analysis, independent predictors of outcome at 1 year were serum levels of Day 7 Pg (favorable GOS-OR 3.24, CI 1.5-7, p = 0.003; and favorable survival-OR 2, CI 1.2-3.5, p = 0.01); admission IL-6 (favorable GOS-OR 1.04, CI 1.00-1.08, p = 0.04); and Day 7 GFAP p = 0.01; p = 0.01). coNclusioNs Serial Pg, GFAP, and IL-6 monitoring could aid in prognosticating outcomes in patients with acute sTBI. A cause and effect relationship or a mere association of these biomarkers to outcome needs to be further studied for better understanding of the pathophysiology of sTBI and for choosing potential therapeutic targets.Clinical trial registration no
OBJECTIVEThe COVID-19 pandemic has forced medical professionals throughout the world to adapt to the changing medical scenario. The objective of this survey was to assess the change in neurosurgical training in India following the COVID-19 pandemic.METHODSBetween May 7, 2020, and May 16, 2020, a validated questionnaire was circulated among neurosurgical residents across India by social media, regarding changes in the department’s functioning, patient interaction, surgical exposure, changes in academics, and fears and apprehensions associated with the pandemic. The responses were kept anonymous and were analyzed for changes during the COVID-19 pandemic compared to before the pandemic.RESULTSA total of 118 residents from 29 neurosurgical training programs across 17 states/union territories of the country gave their responses to the survey questionnaire. The survey revealed that the surgical exposure of neurosurgical residents has drastically reduced since the onset of the COVID-19 pandemic, from an average of 39.86 surgeries performed/assisted per month (median 30) to 12.31 per month (median 10), representing a decrease of 67.50%. The number of academic sessions has fallen from a median of 5 per week to 2 per week. The survey uncovered the lack of universal guidelines and homogeneity regarding preoperative COVID-19 testing. The survey also reveals reluctance toward detailed patient examinations since the COVID-19 outbreak. The majority of respondents felt that the COVID-19 pandemic will hamper their operative and clinical skills. Fear of rescheduling or deferring of licensing examinations was significantly higher among those closest to the examination (p = 0.002).CONCLUSIONSThe adverse impact of the pandemic on neurosurgical training needs to be addressed. While ensuring the safety of the residents, institutes and neurosurgical societies/bodies must take it upon themselves to ensure that their residents continue to learn and develop neurosurgical skills during these difficult times.
The severity of head injury, performing a duraplasty rather than a slit durotomy, avoidance of a contralateral DC, and the presence of preoperative hypotension, infarct, and/or pupillary asymmetry have the highest odds of predicting the short term GOS at the time of discharge, after a DC in patients with TBI. Although DC carries a high risk of mortality, the probability of the survivors having a favorable outcome is significantly more as compared to those who remain in a PVS.
Diffuse midline gliomas (DMGs) are rare and devastating tumors with limited therapeutic options. Programmed death-ligand 1 (PD-L1) expression represents a potential predictive biomarker for immunotherapy. One hundred and twenty-six DMGs (89 adult and 37 pediatric) were assessed for immune profile (PD-L1, cluster of differentiation (CD3, CD8) and genetic markers (mutation in 27th amino acid of histone H3 (H3K27M), alpha thalassemia/mental retardation syndrome X-linked (ATRX), isocitrate dehydrogenase 1 (IDH1), p53) by immunohistochemistry. Sanger sequencing was done for IDH1 and H3K27M. The thalamus was the commonest site. Four molecular subgroups of DMGs were identified. H3K27M mutation was more frequent in children (P = 0.0001). The difference in median overall survival (OS) was not significant in any of the four molecular subgroups (P > 0.05). PD-L1 expression was significantly higher in H3K27M/IDH1 double-negative adult glioblastomas (GBMs) (P = 0.002). Strong PD-L1 expression was more frequent in grade IV tumors and thalamic location, although the difference was not significant (P = 0.14 and P = 0.19 respectively). Positive PD-L1 expression was significantly associated with high tumor-infiltrating lymphocytes count (P < 0.05). There was no significant difference in median OS in PD-L1-positive versus negative cases among four genetic subgroups (P > 0.05). On univariate analysis, there was no direct correlation of PD-L1 with any genetic alteration, except H3K27M mutation (P = 0.01). CD3 infiltration was similar in both adults and pediatric ages (84.3% and 78.4%, respectively) while CD8 expression was significantly greater in adults compared to children (74.1% vs 37.8%, P = 0.0001). This is the first comprehensive analysis highlighting molecular and immune profiles of DMGs. Despite molecular and clinicopathological diversity, overall survival in DMGs remains dismal. Multicentric studies with larger numbers of cases should be undertaken for stratifying DMGs according to their age, immune and molecular profiles, to develop effective immunotherapies.
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