Utility of Simple and Non-Invasive Strategies Alternative to Inferior Petrosal Sinus Sampling and Peripheral CRH Stimulation in Differential Diagnosis of ACTH-Dependent Cushing Syndrome.

We aimed to evaluate the utility of simple, cost-effective, and non-invasive strategies alternative to BIPSS and peripheral CRH stimulation in differential diagnosis of ACTH-dependent CS. First, we performed ROC analysis to evaluate the performance of various tests for differential diagnosis of ACTH-dependent CS in our cohort (CD, n=76 and EAS, n=23) and derived their optimal cut-offs. Subsequently, combining various demographic (gender), clinical (hypokalemia), biochemical (plasma ACTH, HDDST, peripheral CRH stimulation) and imaging (MRI pituitary) parameters, we derived non-invasive models with 100% PPV for CD. Patients with pituitary macroadenoma (n=14) were excluded from the analysis involving non-invasive models. Relative percent ACTH (AUC: 0.933) and cortisol (AUC: 0.975) increase on peripheral CRH stimulation demonstrated excellent accuracy in discriminating CD from EAS. Best cut-offs for CD were plasma ACTH<97.3 pg/ml, HDDST≥57% cortisol suppression, CRH stimulation≥77% ACTH increase and≥11% cortisol increase. We derived six models that provided 100% PPV for CD and precluded the need for BIPPS in 35/85 (41.2%) patients with ACTH-dependent CS and no macroadenoma (in whom BIPSS would have otherwise been recommended). The first three models included basic parameters and avoided both peripheral CRH stimulation and BIPSS in 19 (22.4%) patients, while the next three models included peripheral CRH stimulation and avoided BIPSS in another 16 (18.8%) patients. Using simple and non-invasive alternative strategies, BIPSS can be avoided in 41% and peripheral CRH stimulation in 22% of patients with ACTH-dependent CS and no macroadenoma; such patients can be directly referred for a pituitary surgery.

Non-chordomatous clival bony tumors: A rare experience and systematic literature review.

BACKGROUND: Non-chordomatous bony tumors of the clivus are extremely rare. Site, extent, and aggressiveness of tumor limits the extent of resection. It poses challenge to the neurosurgeons due to the complexity of anatomy. There is paucity of literature exclusively on non-chordomatous bone tumors of the clivus in young adults. OBJECTIVES: To analyze the clinical presentation, imaging findings, surgical approach, complications, and outcome of primary clival bony tumors in young adults. METHODS: We retrospectively reviewed children and young adults with primary clival bony tumors excluding chordoma who underwent surgical resection between years 2010 and 2023 in our center. We analyzed the demographic details, imaging findings, operative variables, perioperative complications, length of stay, complications, and outcome at latest follow-up. RESULTS: The mean age was 17.5 ± 1.73 years (range 16 to 19 years). Headache was the presenting complaint in all four patients (100%). The mean duration of symptom was 7.25 ± 3.2 months (range 5 to 12 months). The tumor was localized in clivus in all four patients (100%). The mean length of stay in hospital was 30.5 ± 13.48 days (range 11 to 40 days). All patients underwent surgical treatment. Surgical approaches used were anterior approach in four patients (100%). Gross total excision was performed in one patient (25%), sub-total excision was performed in two patients (50%), and tumor decompression was performed in one patient (25%). Of these, three were designated as having benign tumors and one had a malignant tumor. There was no perioperative mortality. There was one mortality (25%) on 2 months follow-up due to tumor progression. Three patients (75%) had improved symptomatically at latest follow-up. Two patients (50%) received adjuvant chemoradiotherapy. The mean follow-up was 38 ± 39.29 months (range 2 to 72 months). CONCLUSION: Non-chordomatous bony tumors of the clivus are rare and often underestimated. Surgery is the treatment of choice. Tumor consistency and adhesion to critical neurovascular structures precludes gross total resection. Various approaches are in the armamentarium. Approach to be decided based on the expertise of the neurosurgeon to achieve safe maximal resection. Multidisciplinary approach is mandatory for streamlined management. Adjuvant therapy is decided based on the residual tumor following surgery.

Middle third falcine meningiomas-surgical nuances for cortical venous preservation.

PURPOSE: To improve postoperative outcome in middle third falcine meningiomas by cortical venous preservation. BACKGROUND: Falcine meningiomas arise from the falx and do not involve the superior sagittal sinus (SSS). Their complete resection is often associated with the risk of venous infarction in the eloquent cortex due to overlying superficial cortical veins on the tumors. METHOD: We report one case of middle third falcine meningioma, where we used the posterior interhemispheric corridor for tumor approach. CONCLUSION: Use of the posterior interhemispheric approach, carefully raised bone flap, along with sharp dissection and vein reinforcement using fibrin glue can help to preserve the cortical veins while resecting the falcine meningiomas.

Evaluation of KIAA1549::BRAF fusions and clinicopathological insights of pilocytic astrocytomas.

BACKGROUND: Pilocytic astrocytoma (PAs) represents a significant portion of childhood primary brain tumors, with distinct histological and radiological features. The prevalence of KIAA1549::BRAF fusion in PAs has been well-established, this study aims to assess the prevalence of KIAA1549::BRAF fusions and explore their associations with tumor characteristics, radiological findings, and patient outcomes in PAs. METHODS: Histologically confirmed cases of PAs from a 5-year period were included in the study. Demographic, histopathological, and radiological data were collected, and immunohistochemistry was performed to characterize tumor markers. FISH and qRT-PCR assays were employed to detect KIAA1549::BRAF fusions. Statistical analyses were conducted to examine associations between fusion status and various other parameters. RESULTS: Histological analysis revealed no significant differences in tumor features based on fusion status. However, younger age groups showed higher fusion prevalence. Radiologically, fusion-positive cases were distributed across different tumor subtypes SE, CWE and NCWE. Survival analysis did not demonstrate a significant impact of fusion status on overall survival, however most cases with recurrence and death harboured KIAA1549::BRAF fusion. Of 200 PAs, KIAA1549::BRAF fusions were detected in 64 % and 74 % of cases via qRT-PCR and FISH, respectively. Concordance between the two platforms was substantial (86 %). CONCLUSION: KIAA1549::BRAF fusions are prevalent in PAs and can be reliably detected using both FISH and qRT-PCR assays. Cost considerations suggest qRT-PCR as a more economical option for fusion detection in routine clinical practice.

Protumorigenic role of the atypical cadherin FAT1 by the suppression of PDCD10 via RelA/miR221-3p/222-3p axis in glioblastoma.

The atypical cadherin FAT1 function either as a pro or antitumorigenic in tumors of different tissue origins. Our group previously demonstrated the protumorigenic nature of FAT1 signaling in glioblastoma (GBM). In this study, we investigated how FAT1 influences the expression of clustered oncomiRs (miR-221-3p/miR-222-3p) and their downstream effects in GBM. Through several experiments involving the measurement of specific gene/microRNA expression, gene knockdowns, protein and cellular assays, we have demonstrated a novel oncogenic signaling pathway mediated by FAT1 in glioma. These results have been verified using antimiRs and miR-mimic assays. Initially, in glioma-derived cell lines (U87MG and LN229), we observed FAT1 as a novel up-regulator of the transcription factor NFκB-RelA. RelA then promotes the expression of the clustered-oncomiRs, miR-221-3p/miR-222-3p, which in turn suppresses the expression of the tumor suppressor gene (TSG), PDCD10 (Programmed cell death protein10). The suppression of PDCD10, and other known TSG targets (PTEN/PUMA), by miR-221-3p/miR-222-3p, leads to increased clonogenicity, migration, and invasion of glioma cells. Consistent with our in-vitro findings, we observed a positive expression correlation of FAT1 and miR-221-3p, and an inverse correlation of FAT1 and the miR-targets (PDCD10/PTEN/PUMA), in GBM tissue-samples. These findings were also supported by publicly available GBM databases (The Cancer Genome Atlas [TCGA] and The Repository of Molecular Brain Neoplasia Data [Rembrandt]). Patients with tumors displaying high levels of FAT1 and miR-221-3p expression (50% and 65% respectively) experienced shorter overall survival. Similar results were observed in the TCGA-GBM database. Thus, our findings show a novel FAT1/RelA/miR-221/miR-222 oncogenic-effector pathway that downregulates the TSG, PDCD10, in GBM, which could be targeted therapeutically in a specific manner.

DNA methylation profiling of meningiomas highlights clinically distinct molecular subgroups.

BACKGROUND: Introduction of the classification of brain tumours based on DNA methylation profile has significantly changed the diagnostic approach. Due to the paucity of data on the molecular profiling of meningiomas and their clinical implications, no effective therapies and new treatments have been implemented. METHODS: DNA methylation profiling, copy number analysis, targeted sequencing and H3K27me3 expression was performed on 35 meningiomas and 5 controls. RESULTS: Unsupervised hierarchical clustering (UHC) analysis revealed four distinct molecular subgroups: Malignant; Intermediate; Benign A, and Benign B. Molecular heterogeneity was observed within the same grade as the Intermediate, Benign A, and Benign B subgroups were composed of WHO grade 1 as well as grade 2 cases. There was association of mutations with distinct methylation subgroups (NF2, AKT1, SMO, TRAF7 and pTERT). Loss of chromosome 22q was observed across all subgroups. 1p/14q co-deletion was seen in 50% of malignant and intermediate while CDKN2A loss was predominantly observed in malignant subgroup (50%). Majority of malignant (75%) and a small proportion of other subgroups (Intermediate: 25%, Benign A: 38.5%, and Benign B: 20%) harboured H3K27me3 loss. 38,734 genes were dysregulated amongst the four subgroups. DKFZ classified 71% cases with acceptable score. On survival analysis, methylation profiling had significant impact on progression-free-survival in WHO grade1 and 2 meningiomas (p = 0.0051). CONCLUSION: Genome-wide DNA methylation profiling highlights clinically distinct molecular subgroups and heterogeneity within the same grade of meningiomas. Molecular profiling can usher in a paradigm shift in meningioma classification, prognostic prediction, and treatment strategy.

Comprehensive Outcome Assessment and Quality of Life Following Epilepsy Surgery.

BACKGROUND: Seizure freedom without deficits is the primary goal for epilepsy surgery. However, patients with medically refractory epilepsy commonly suffer from many co-morbidities related to mood, cognition, and sleep as well as social problems and resultant stigma. While epilepsy surgery literature does describe quality of life (QOL) and neuropsychological outcomes, there is a paucity of information on various common non-seizure outcomes, especially pertaining to mood, sleep, cognition, and social aspects. The objective of this study was to evaluate the role of various non-seizure parameters on post-epilepsy surgery QOL. METHODS: Consecutive adult patients operated for refractory epilepsy at least 1 year prior to initiation of this study were included and classified as seizure-free (group 1) or non-seizure-free (group 2). QOL was assessed using the QOLIE-31 instrument; patients with a T score less than 40 were categorized as "poor QOL." Non-seizure parameters assessed were cognition, mood disturbances, social improvement, social stigma, and sleep disturbances. Categorization into "good" and "poor" outcome subgroups on each item was carried out by dichotomization of scores. RESULTS: Thirty-seven patients (16 F) [mean age 23.5 ± 5.6 years] were evaluated; 26 were seizure-free (group 1). In this group, impaired memory, lower language scores, depression, not having been employed, not receiving education prior to surgery, and experiencing social stigma were factors significantly associated with poor QOL. In group 2, all patients had poor QOL scores. CONCLUSION: Non-seizure factors related to common epilepsy co-morbidities and social issues are highly prevalent among seizure-free patients reporting poor QOL after epilepsy surgery.

Microsurgical suturing assessment scores: a systematic review.

Several scoring scales for the assessment of microsurgical skills have been established and validated with the same basic parameters. The study aims to review the existing scales to highlight those parameters, which can be utilized uniformly across all neurosurgical training centers. An online search was conducted and all the surgical scores pertinent to microsurgical suturing were reviewed. The scales were compared to identify parameters, which were important for skill development and assessment in neurosurgical trainees. Seven assessment scales were identified which assessed the trainee's proficiency in microsurgical suturing. The objective structured assessment of technical skills (OSATS) and Northwestern Objective Microanastomosis Assessment Tool (NOMAT) were identified as the most widely used and validated assessment scales. The newer scales University of Western Ontario microsurgical skills acquisition/assessment (UWOMSA) and structured assessment of microsurgery (SAMS) were notable for the division of the skills. The knot strength, suture separation, and suture intervals were the most important parameters in all scales. Each scale has its strength in the assessment of the microsurgical proficiency of neurosurgical trainees. However, a more uniform scale that can be applied as per the level of the neurosurgical trainee is necessary.

Interval assessment using task- and procedure-based simulations: an attempt to supplement neurosurgical residency curriculum.

OBJECTIVE: The longer learning curve and smaller margin of error make nontraditional, or "out of operating room" simulation training, essential in neurosurgery. In this study, the authors propose an evaluation system for residents combining both task-based and procedure-based exercises and also present the perception of residents regarding its utility. METHODS: Residents were evaluated using a combination of task-based and virtual reality (VR)-based exercises. The results were analyzed in terms of the seniority of the residents as well as their laboratory credits. Questionnaire-based feedback was sought from the residents regarding the utility of this evaluation system incorporating the VR-based exercises. RESULTS: A total of 35 residents were included in this study and were divided into 3 groups according to seniority. There were 11 residents in groups 1 and 3 and 13 residents in group 2. On the overall assessment of microsuturing skills including both 4-0 and 10-0 microsuturing, the suturing skills of groups 2 and 3 were observed to be better than those of group 1 (p = 0.0014). Additionally, it was found that microsuturing scores improved significantly with the increasing laboratory credits (R2 = 0.72, p < 0.001), and this was found to be the most significant for group 1 residents (R2 = 0.85, p < 0.001). Group 3 residents performed significantly better than the other two groups in both straight (p = 0.02) and diagonal (p = 0.042) ring transfer tasks, but there was no significant difference between group 1 and group 2 residents (p = 0.35). Endoscopic evaluation points were also found to be positively correlated with previous laboratory training (p = 0.002); however, for the individual seniority groups, the correlation failed to reach statistical significance. The 3 seniority groups performed similarly in the cranial and spinal VR modules. Group 3 residents showed significant disagreement with the utility of the VR platform for improving surgical dexterity (p = 0.027) and improving the understanding of surgical procedures (p = 0.034). Similarly, there was greater disagreement for VR-based evaluation to identify target areas of improvement among the senior residents (groups 2 and 3), but it did not reach statistical significance (p = 0.194). CONCLUSIONS: The combination of task- and procedure-based assessment of trainees using physical and VR simulation models can supplement the existing neurosurgery curriculum. The currently available VR-based simulations are useful in the early years of training, but they need significant improvement to offer beneficial learning opportunities to senior trainees.

Role of CDKN2A deletion in grade 2/3 IDH-mutant astrocytomas: need for selective approach in resource-constrained settings.

OBJECTIVE: The authors aimed to assess the frequency of homozygous CDKN2A deletion in isocitrate dehydrogenase (IDH)-mutant diffuse astrocytomas (grade 2/3) and to narrow down the clinicopathological indications in which the CDKN2A fluorescence in situ hybridization (FISH) assay is cost-effective in resource-constrained settings. METHODS: IDH-mutant astrocytomas were analyzed for ATRX, p53, MIB1-LI, and p16 expression using immunohistochemistry. The FISH assay was used to evaluate CDKN2A deletion and 1p/19q codeletion. Survival outcomes were assessed according to the different molecular markers. RESULTS: A total of 150 adult patients with IDH-mutant grade 2 (n = 95) and grade 3 (n = 55) astrocytomas (145 primary and 5 recurrent) were analyzed. Using a cutoff value of 30% for defining significant homozygous CDKN2A deletion, none of the grade 2 and 10.9% (6/55) of grade 3 astrocytomas showed this deletion (4 primary and 2 recurrent grade 3 tumors) and were reclassified as grade 4. This mutation was more frequent in recurrent (40%, 2/5) than primary (2.76%, 4/145) gliomas. Half (3/6, 50%) of the CDKN2A-deleted cases demonstrated poor outcomes; 2 of these cases experienced recurrence at 12 and 36 months after surgery, and 1 died at 5 months. The majority of CDKN2A-deleted cases showed marked cellularity (100%), pleomorphism (100%), brisk mitosis (83.3%), and tumor giant cell formation (83.4%). None of the cases with retained p16 expression harbored this deletion. Both overall survival (p = 0.039) and progression-free survival (p = 0.0045) were found to be worse in cases with p16 loss. Selectively performing CDKN2A FISH only in high-risk cases with histomorphological features of anaplasia, p16 loss, or recurrent tumors achieved a sensitivity and negative predictive value of 100%. This approach would have resulted in saving 41.1% of the original expenditure ($6900 US per 150 samples) and 27.6 person-minutes per sample without compromising the identification of deleted cases. CONCLUSIONS: Homozygous CDKN2A deletion is conspicuously absent in grade 2 and rare in primary grade 3 IDH-mutant astrocytomas. The authors propose that restricting use of the FISH assay to cases showing histomorphological features of anaplasia, p16 loss, or recurrent tumors will help this platform to be utilized in the most cost-effective manner in resource-constrained settings.

Challenges and prospects of neurosurgical teleconsultations in a developing country: a reality check.

OBJECTIVE: The adoption of telemedicine became a necessity during the COVID-19 pandemic because patients found commuting to be difficult owing to travel restrictions. Initially, audio-based teleconsultations were provided. Later, on the basis of the feedback of patients and caregivers, the authors started to provide video-based teleconsultations via WhatsApp. The authors subsequently surveyed the patients and caregivers to determine their satisfaction levels with telemedicine services. METHODS: An anonymized telephone survey of patients who had participated in teleconsultation was conducted with a structured questionnaire. The responses were analyzed and their correlations with the perceived benefits and limitations of audio and video teleconsultation were determined. RESULTS: Three hundred respondents were included in the first round of surveys, of whom 250 (83.3%) consented to video teleconsultation. Among the respondents who participated in both audio and video teleconsultations (n = 250), paired analysis showed that video teleconsultation was perceived as better in terms of providing easier access to healthcare services (p < 0.001), saving time (p < 0.001), and satisfaction with the way patient needs were conveyed to healthcare providers (p = 0.023), as well as in terms of adequacy of addressing healthcare needs (p < 0.001) and consequently providing a higher rate of overall satisfaction (p < 0.001). For both audio and video teleconsultation, overall patient satisfaction was significantly related to only previous exposure to WhatsApp. However, for video consultation, longer call duration (p = 0.023) was an important independent factor. Video teleconsultation was preferable to face-to-face consultation irrespective of educational status, but higher education was associated with preference for video teleconsultation. CONCLUSIONS: Both audio and video teleconsultation are viable cost-effective surrogates for in-person physical neurosurgical consultation. Although audio teleconsultation is more user-friendly and is not restricted by educational status, video teleconsultation trumps the former owing to a more efficient and satisfactory doctor-to-patient interface.

Clinico-pathological and molecular characterization of diffuse midline gliomas: is there a prognostic significance?

PURPOSE: H3K27M mutant diffuse midline gliomas (DMGs) are considered grade IV irrespective of histological features and have dismal prognosis. We evaluated clinico-pathologic, radiological, and molecular characteristics of DMGs across all ages. METHODS: One twenty-six DMGs were identified over 10 years. Immunohistochemistry was done for H3K27M, ATRX, IDH1, and p53, and Sanger sequencing performed for IDH1 and H3K27M mutation. Patient demographics and clinico-radiologic characteristics were reviewed and survival analysis performed. RESULTS: DMGs comprised 5.3% of all gliomas with 49.2% H3K27M mutant and 50.8% wild types. Majority (75.68%) of pediatric and 38.20% of adults were H3K27M mutant (p = 0.0001). Amongst H3K27M mutants, brainstem (46.43%) was the commonest location in pediatric and thalamus (61.76%) in adults. H3K27M mutation was mutually exclusive with IDH mutation in 93.55%, while p53, ATRX mutation were seen in 56.4% and 30.6% cases respectively. Software-based immunohistochemistry evaluation (H-scoring) showed 99.2% concordance with sequencing for H3K27M mutation. Radiologically, no significant difference in contrast enhancement was seen between mutant and wild types (p = 0.05). The difference in overall survival (OS) was not significant in mutant versus wild types, with age or location. Tumor resection independently and on correlation with H3K27M did not influence OS (p = 0.51 and p = 0.47). Adjuvant therapy impacted survival significantly in adults (p = 0.0009), however, not in pediatric cases (p = 0.06). CONCLUSIONS: The study highlights the differences in frequency and location of pediatric and adult DMGs. IHC (H-scoring) for H3K27M mutation is an excellent surrogate for sequencing. Prognosis remains dismal irrespective of age, location, and H3K27M status. Potential therapeutic targets need to be explored.

Impact of different visualization devices on accuracy, efficiency, and dexterity in neurosurgery: a laboratory investigation.

OBJECTIVE: Extracorporeal telescopes (exoscopes) have been the latest addition to the neurosurgeons' armamentarium, acting as a bridge between operating microscopes and endoscopes. However, to the authors' knowledge there are no published preclinical laboratory studies of the accuracy, efficiency, and dexterity of neurosurgical training for the use of 2D or 3D exoscopes compared with microscopes. METHODS: In a controlled experimental setup, 22 participating neurosurgery residents performed simple (2D) and complex (3D) motor tasks with three visualization tools in alternating sequence: a 2D exoscope, 3D exoscope, and microscope, using a block randomization model based on the neurosurgeons' prior training experience (novice, intermediate, and senior: n = 6, 12, and 4, respectively). Performance scores (PS; including error and efficiency scores) and dexterity scores (DS) were calculated to objectify the accuracy, efficiency, and finesse of task performance. Repeated measures ANOVA analysis was used to compare the PS, DS, and cumulative scores (CS) of candidates using the three visualization aids. Bland-Altman plots and intraclass correlation coefficients were generated to quantify intraobserver and interobserver agreement for DS. Subgroup analysis was performed to assess the impact of participants' prior training. A postexercise survey was conducted to assess the comfort level (on a 10-point analog scale) of the participants while using each visualization tool for performing the suturing task. RESULTS: PS, DS, and CS were significantly impacted by the visualization tool utilized for 2D motor tasks (p < 0.001 for each), with the microscope faring better than the 2D exoscope (p = 0.04) or 3D exoscope (p = 0.008). The PS for the 3D object transfer task was significantly influenced by the visualization aid used (p = 0.007), with the microscope and 3D exoscope faring better than the 2D exoscope (p = 0.04 for both). The visualization instrument used significantly affected the DS and CS for the suturing task (p < 0.001 for both), with the microscope again scoring better than the 2D exoscope (p < 0.001) or 3D exoscope (p = 0.005). The impact of the visualization aid was more apparent in participants with a shorter duration of residency (novice, p = 0.03; intermediate, p = 0.0004). Participants also felt the greatest operational comfort while working with a microscope, 3D exoscope, and 2D exoscope, in that order (p < 0.0001). CONCLUSIONS: Compared with 3D and 2D exoscopes, an operating microscope provides better dexterity and performance and a greater operational comfort level for neurosurgeons while they are performing 2D or 3D motor tasks. For performing complex 3D motor tasks, 3D exoscopes offer selective advantages in dexterity, performance, and operational comfort level over 2D exoscopes. The relative impact of visualization aids on surgical proficiency gradually weakens as the participants' residency duration increases.

NFкB is a critical transcriptional regulator of atypical cadherin FAT1 in glioma.

BACKGROUND: Overexpression of FAT1 gene and its oncogenic effects have been reported in several cancers. Previously, we have documented upregulation of FAT1 gene in glioblastoma (GBM) tumors which was found to increase the expression of proinflammatory markers, HIF-1α, stemness genes and EMT markers in glioma cells. Here, we reveal NFкB (RelA)/RelA/p65 as the transcriptional regulator of FAT1 gene in GBM cells. METHODS: In-silico analysis of FAT1 gene promoter was performed using online bioinformatics tool Promo alggen (Transfac 8.3) to identify putative transcription factor(s) binding motifs. A 4.0 kb FAT1 promoter (- 3220 bp to + 848 bp w.r.t. TSS + 1) was cloned into promoter less pGL3Basic reporter vector. Characterization of FAT1 promoter for transcriptional regulation was performed by in-vitro functional assays using promoter deletion constructs, site directed mutagenesis and ChIP in GBM cells. RESULTS: Expression levels of NFкB (RelA) and FAT1 were found to be increased and positively correlated in GBM tumors (n = 16), REMBRANDT GBM-database (n = 214) and TCGA GBM-database (n = 153). In addition to glioma, positive correlation between NFкB (RelA) and FAT1 expression was also observed in other tumors like pancreatic, hepatocellular, lung and stomach cancers (data extracted from TCGA tumor data). A 4.0 kb FAT1-promoter-construct [- 3220 bp/+ 848 bp, transcription start site (TSS) + 1, having 17 NFкB (RelA) motifs] showed high FAT1 promoter luciferase-activity in GBM cells (U87MG/A172/U373MG). FAT1 promoter deletion-construct pGL3F1 [- 200 bp/+ 848 bp, with 3-NFкB (RelA)-motifs] showed the highest promoter activity. Exposure of GBM cells to known NFкB (RelA)-activators [severe-hypoxia/TNF-α/ectopic-NFкB (RelA) + IKBK vectors] led to increased pGL3F1-promoter activity and increased endogenous-FAT1 expression. Conversely, siRNA-mediated NFкB (RelA) knockdown led to decreased pGL3F1-promoter activity and decreased endogenous-FAT1 expression. Deletion of NFкB (RelA)-motif at - 90 bp/- 80 bp [pGL3F1δ1-construct] showed significant decrease in promoter activity. Site directed mutagenesis at -90 bp/- 80 bp and ChIP assay for endogenous-NFкB (RelA) confirmed the importance of this motif in FAT1 expression regulation. Significant reduction in the migration, invasion as well as colony forming capacity of the U87MG glioma cells was observed on siRNA-mediated knockdown of NFкB (RelA). CONCLUSION: Since FAT1 and NFкB (RelA) are independently known to promote pro-tumorigenic inflammation and upregulate the expression of HIF-1α/EMT/stemness in tumors, targeting the NFкB (RelA)-FAT1 axis may attenuate an important tumor-promoting pathway in GBM. This may also be applicable to other tumors.

Cranial and ventricular size following shunting or endoscopic third ventriculostomy (ETV) in infants with aqueductal stenosis: further insights from the International Infant Hydrocephalus Study (IIHS).

PURPOSE: The craniometrics of head circumference (HC) and ventricular size are part of the clinical assessment of infants with hydrocephalus and are often utilized in conjunction with other clinical and radiological parameters to determine the success of treatment. We aimed to assess the effect of endoscopic third ventriculostomy (ETV) and shunting on craniometric measurements during the follow-up of a cohort of infants with symptomatic triventricular hydrocephalus secondary to aqueductal stenosis. METHODS: We performed a post hoc analysis of data from the International Infant Hydrocephalus Study (IIHS)-a prospective, multicenter study of infants (< 24 months old) with hydrocephalus from aqueductal stenosis who were treated with either an ETV or shunt. During various stages of a 5-year follow-up period, the following craniometrics were measured: HC, HC centile, HC z-score, and frontal-occipital horn ratio (FOR). Data were compared in an analysis of covariance, adjusting for baseline variables including age at surgery and sex. RESULTS: Of 158 enrolled patients, 115 underwent an ETV, while 43 received a shunt. Both procedures led to improvements in the mean HC centile position and z-score, a trend which continued until the 5-year assessment point. A similar trend was noted for FOR which was measured at 12 months and 3 years following initial treatment. Although the values were consistently higher for ETV compared with shunt, the differences in HC value, centile, and z-score were not significant. ETV was associated with a significantly higher FOR compared with shunting at 12 months (0.52 vs 0.44; p = 0.002) and 3 years (0.46 vs 0.38; p = 0.03) of follow-up. CONCLUSION: ETV and shunting led to improvements in HC centile, z-score, and FOR measurements during long-term follow-up of infants with hydrocephalus secondary to aqueductal stenosis. Head size did not significantly differ between the treatment groups during follow-up, however ventricle size was greater in those undergoing ETV when measured at 1 and 3 years following treatment.

A review of virtual reality simulators for neuroendoscopy.

Neurosurgery is a challenging surgical specialty that demands many technical and cognitive skills. The traditional surgical training approach of having a trainee coached in the operating room by the faculty is time-consuming, costly, and involves patient risk factors. Simulation-based training methods are suitable to impart the surgical skills outside the operating room. Virtual simulators allow high-fidelity repeatable environment for surgical training. Neuroendoscopy, a minimally invasive neurosurgical technique, demands additional skills for limited maneuverability and eye-hand coordination. This study provides a review of the existing virtual reality simulators for training neuroendoscopic skills. Based on the screening, the virtual training methods developed for neuroendoscopy surgical skills were classified into endoscopic third ventriculostomy and endonasal transsphenoidal surgery trainers. The study revealed that a variety of virtual reality simulators have been developed by various institutions. Although virtual reality simulators are effective for procedure-based skills training, the simulators need to include anatomical variations and variety of cases for improved fidelity. The review reveals that there should be multi-centric prospective and retrospective cohort studies to establish concurrent and predictive validation for their incorporation in the surgical educational curriculum.

Impact of frailty on surgery for glioblastoma: a critical evaluation of patient outcomes and caregivers' perceptions in a developing country.

OBJECTIVE: The authors aimed to evaluate the impact of age and frailty on the surgical outcomes of patients with glioblastoma (GBM) and to assess caregivers' perceptions regarding postdischarge care and challenges faced in the developing country of India. METHODS: This was a retrospective study of patients with histopathologically proven GBM from 2009 to 2018. Data regarding the clinical and radiological characteristics as well as surgical outcomes were collected from the institute's electronic database. Taking Indian demographics into account, the authors used the cutoff age of 60 years to define patients as elderly. Frailty was estimated using the 11-point modified frailty index (mFI-11). Patients were divided into three groups: robust, with an mFI score of 0; moderately frail, with an mFI score of 1 or 2; and severely frail, with an mFI score ≥ 3. A questionnaire-based survey was done to assess caregivers' perceptions about postdischarge care. RESULTS: Of the 276 patients, there were 93 (33.7%) elderly patients and 183 (66.3%) young or middle-aged patients. The proportion of severely frail patients was significantly more in the elderly group (38.7%) than in the young or middle-aged group (28.4%) (p < 0.001). The authors performed univariate and multivariate analysis of associations of different short-term outcomes with age, sex, frailty, and Charlson Comorbidity Index. On the multivariate analysis, only frailty was found to be a significant predictor for in-hospital mortality, postoperative complications, and length of hospital and ICU stay (p < 0.001). On Cox regression analysis, the severely frail group was found to have a significantly lower overall survival rate compared with the moderately frail (p = 0.001) and robust groups (p < 0.001). With the increase in frailty, there was a concomitant increase in the requirement for readmissions (p = 0.003), postdischarge specialist care (p = 0.001), and help from extrafamilial sources (p < 0.001). Greater dissatisfaction with psychosocial and financial support among the caregivers of severely frail patients was seen as they found themselves ill-equipped to provide postdischarge care at home (p < 0.001). CONCLUSIONS: Frailty is a better predictor of poorer surgical outcomes than chronological age in terms of duration of hospital and ICU stay, postoperative complications, and in-hospital mortality. It also adds to the psychosocial and financial burdens of the caregivers, making postdischarge care challenging.

Preparedness and guidelines for neurosurgery in the COVID-19 era: Indian perspective from a tertiary care referral hospital.

The COVID-19 pandemic has severely impacted healthcare systems globally. The need of the hour is the development of effective strategies for protecting the lives of healthcare providers (HCPs) and judicious triage for optimal utilization of human and hospital resources. During this pandemic, neurosurgery, like other specialties, must transform, innovate, and adopt new guidelines and safety protocols for reducing the risk of cross-infection of HCPs without compromising patient care. In this article, the authors discuss the current neurosurgical practice guidelines at a high-volume tertiary care referral hospital in India and compare them with international guidelines and global consensus for neurosurgery practice in the COVID-19 era. Additionally, the authors highlight some of the modifications incorporated into their clinical practice, including those for stratification of neurosurgical cases, patient triaging based on COVID-19 testing, optimal manpower management, infrastructure reorganization, evolving modules for resident training, and innovations in operating guidelines. The authors recommend the use of their blueprint for stratification of neurosurgical cases, including their protocol for algorithmic patient triage and management and their template for manpower allocation to COVID-19 duty, as a replicable model for efficient healthcare delivery.

Surgical management for large vestibular schwannomas: a systematic review, meta-analysis, and consensus statement on behalf of the EANS skull base section.

BACKGROUND AND OBJECTIVE: The optimal management of large vestibular schwannomas continues to be debated. We constituted a task force comprising the members of the EANS skull base committee along with international experts to derive recommendations for the management of this problem from a European perspective. MATERIAL AND METHODS: A systematic review of MEDLINE database, in compliance with the PRISMA guidelines, was performed. A subgroup analysis screening all surgical series published within the last 20 years (January 2000 to March 2020) was performed. Weighted summary rates for tumor resection, oncological control, and facial nerve preservation were determined using meta-analysis models. This data along with contemporary practice patterns were discussed within the task force to generate consensual recommendations regarding preoperative evaluations, optimal surgical strategy, and follow-up management. RESULTS: Tumor classification grades should be systematically used in the perioperative management of patients, with large vestibular schwannomas (VS) defined as > 30 mm in the largest extrameatal diameter. Grading scales for pre- and postoperative hearing (AAO-HNS or GR) and facial nerve function (HB) are to be used for reporting functional outcome. There is a lack of consensus to support the superiority of any surgical strategy with respect to extent of resection and use of adjuvant radiosurgery. Intraoperative neuromonitoring needs to be routinely used to preserve neural function. Recommendations for postoperative clinico-radiological evaluations have been elucidated based on the surgical strategy employed. CONCLUSION: The main goal of management of large vestibular schwannomas should focus on maintaining/improving quality of life (QoL), making every attempt at facial/cochlear nerve functional preservation while ensuring optimal oncological control, thereby allowing to meet patient expectations. Despite the fact that this analysis yielded only a few Class B evidences and mostly expert opinions, it will guide practitioners to manage these patients and form the basis for future clinical trials.

Impact of Continuous Education and Training in Reduction of Central Line-associated Bloodstream Infection in Neurointensive Care Unit.

BACKGROUND: Patients in the neurointensive care unit have high utilization of devices, thereby increased chance of getting device-associated infection (DAI). Central line-associated bloodstream infection (CLABSI) remains one of the most important DAI. Education remains an important part of the hospital infection control and improves the infection-control practices. MATERIALS AND METHODS: To evaluate the effectiveness of a quality initiative in reducing incidence of CLABSI, a prospective study (January 2017-December 2018) was done estimating CLABSI incidence before and after the intervention. Continuous teaching and training for hand hygiene practice and central-line catheter hub care were used as the tool for this study. RESULTS: The quality improvement (QI) initiative achieved a 48% reduction in the CLABSI rate from the baseline rate of 8.7 to 4.5 per 1000 catheter days. The overall mortality showed a reduction from 1.5 to 0.05% during the post-intervention period. There was a significant improvement in compliance with the hand hygiene practice and catheter hub care in the post-intervention period. DISCUSSION AND CONCLUSION: This study demonstrates adherence to hand hygiene and catheter hub care with continuous teaching, training, and supervision was highly effective in reducing the CLABSI rate. CLINICAL SIGNIFICANCE: Central line-associated bloodstream infection is one of the most important DAI causing significant morbidity and mortality in critically ill patient. Our findings support that continuous educational intervention of hand hygiene with and training on the catheter hub care are two most important preventive measures in the reduction of CLABSI incidence. HOW TO CITE THIS ARTICLE: Mohapatra S, Kapil A, Suri A, Pandia MP, Bhatia R, Borkar S, et al. Impact of Continuous Education and Training in Reduction of Central Line-associated Bloodstream Infection in Neurointensive Care Unit. Indian J Crit Care Med 2020;24(6):414-417.