Surgical Management of Extradural Tumors at the Cranio-Vertebral Junction - Insights from a Tertiary Care Centre.

BACKGROUND: Craniovertebral junction tumors are challenging due to their unique anatomical location. This study aimed to evaluate the complexities in dealing with such precarious craniovertebral junction extradural lesions over the decade. METHODS: 27 patients of extradural CVJ tumors operated between 2009-2018 were included. The demographic details, neurological status, surgical approach, extent of resection, type of fixation, complications and outcome at final follow-up were recorded for each patient. RESULTS: The mean age of the patients was 39.5 +/- 20 years. Most (17/27) of the patients had involvement of a single level. Clivus was the most common (9/17) involved region followed by atlas (7/17) vertebrae. Majority of the patients (13/27) were operated through the posterior-only approach. About 15 patients (55.5%) had instability or extensive lesions that necessitated posterior fixation. None of the patients underwent anterior fixation. Gross and near total excision were achieved in 10 patients (37%) and 3 patients (11 %) respectively while 14 patients underwent subtotal excision of tumor. On histopathological analysis, clival chordoma (8/27) was found to be the most common pathology followed by giant cell tumor (6/27), plasmacytoma (4/27) and multiple myeloma (2/27). Most patients (13 out of 27) had the same neurological status after the surgery. Six patients (22%) improved post-operatively with decreased weakness and spasticity. Thirteen (48%) patients underwent adjuvant radiotherapy. CONCLUSION: This retrospective study provides valuable insights into managing extradural CVJ tumors and highlights the importance of individualized approaches for optimal outcome.

Cisternostomy - As An Adjuvant Or Standalone Approach For Management Of Traumatic Brain Injury: A Systematic Review And Network Meta-Analysis.

BACKGROUND: Traumatic brain injury (TBI) is a leading cause of morbidity in all age groups worldwide. Decompressive craniectomy (DC) is a salvage procedure in patients with TBI. Outcome and quality of life following DC is questionable. Basal cisternostomy (BC) has been proposed to reduce edema and leads to brain relaxation. It was initially used as an adjunct in TBI patients, thereby improving outcome. With gaining popularity among the neurosurgeons, BC was used as a standalone approach in TBI patients. The aim of this network meta-analysis is to analyse the role of BC either as an adjunct or as a standalone approach in managing TBI patients. METHODS: A comprehensive search of electronic databases (PubMed and SCOPUS) was performed using the search strategy using the field terms and medical subheading terms (MeSH Terms) to retrieve studies describing the role of BC in patients with TBI either as an adjunct with DC or standalone treatment and their outcome. RESULTS: Thirty-one articles were selected for full text review and eighteen articles were selected for the final analysis. BC alone group were found to have minimum in-hospital mortality (odds ratio [OR], 0.348; 95% credible interval [CrI], 0.254 to 0.477) followed by DC combined with BC group (OR, 0.645; 95% CrI, 0.476 to 0.875). DC combined with BC group were found to have minimum duration of mechanical ventilation (OR, 0.114; 95% CrI, 0.005 to 2.451) followed by BC alone group (OR, 0.604; 95% CrI, 0.024 to 15.346). DC combined with BC group were found to have maximum Glasgow outcome scale (GOS) (OR, 1.661; 95% CrI, 0.907 to 3.041) followed by BC alone group (OR, 1.553; 95% CrI, 0.907 to 3.041). CONCLUSION: Our analysis showed that BC alone was associated with lower in-hospital mortality rates in TBI patients. DC with BC had decreased requirement of mechanical ventilation. However, larger multicentric studies from other parts of the world are required to confirm these findings.

Re-Admissions of 'Unknown' Traumatic Brain Injury Patients - Inadequacy of Rehabilitative Services in a Developing Country.

BACKGROUND: In neurosurgical practice, continuous care after discharge and the ability to detect subtle indicators of clinical deterioration are mandatory to prevent the progression of a disease. The care of 'unknown' patients discharged to rehabilitation homes may not have this privilege, especially in resource-poor countries such as India. OBJECTIVE: We have attempted to study the causes and outcomes of re-admissions of 'unknown' patients with previous traumatic brain injury (TBI) to estimate the quality of nursing care in our rehabilitation centers. MATERIAL AND METHODS: The electronic hospital records of all consecutive 'unknown' TBI patients with unplanned re-admissions at our institute from January 2014 to December 2018 were retrospectively reviewed and analyzed for the factors determining the risk and outcomes of re-admission. RESULTS: Out of 245 patients sent to rehabilitation homes at discharge, 47 patients (19.18%) were re-admitted. A total of 33 patients (70%) were re-admitted between 1 month and 1 year. Out of these, 38 patients (80.9%) were re-admitted because of preventable causes. Fifteen patients (31.9%) died during the hospital stay. The rest of the 32 (68%) patients were discharged after the management of the concerned condition with an average hospital stay of 9 ± 11.1 days. The average Glasgow coma scale (GCS) at re-admission of the patients who died was 6 (range 3-11). Two patients were brought in the brain dead status, whereas 20 patients (42.6%) had a GCS of 5 or below at the time of re-admission. The risk of mortality among patients with non-preventable causes was 88.9% (8/9) compared to preventable causes 18.4% (7/38). However, preventable causes for re-admission are much more common, resulting in nearly a similar overall contribution to mortality. CONCLUSIONS: There is a high rate of mortality and morbidity in 'unknown' patients with TBI because of poor post-discharge care in developing countries. Because preventable causes are the major contributor to re-admissions, the re-admission rate is a good indicator of a lack of adequate rehabilitative services. The need for improving the post-discharge management of 'unknown' patients with TBI in resource-poor countries cannot be over-emphasized.

Three dimensional convolutional neural network-based automated detection of midline shift in traumatic brain injury cases from head computed tomography scans.

Objectives: Midline shift (MLS) is a critical indicator of the severity of brain trauma and is even suggestive of changes in intracranial pressure. At present, radiologists have to manually measure the MLS using laborious techniques. Automatic detection of MLS using artificial intelligence can be a cutting-edge solution for emergency health-care personnel to help in prompt diagnosis and treatment. In this study, we sought to determine the accuracy and the prognostic value of our screening tool that automatically detects MLS on computed tomography (CT) images in patients with traumatic brain injuries (TBIs). Materials and Methods: The study enrolled TBI cases, who presented at the Department of Neurosurgery, All India Institute of Medical Sciences, New Delhi. Institutional ethics committee permission was taken before starting the study. The data collection was carried out for over nine months, i.e., from January 2020 to September 2020. The data collection included head CT scans, patient demographics, clinical details as well as radiologist's reports. The radiologist's reports were considered the "gold standard" for evaluating the MLS. A deep learning-based three dimensional (3D) convolutional neural network (CNN) model was developed using 176 head CT scans. Results: The developed 3D CNN model was trained using 156 scans and was tested on 20 head CTs to determine the accuracy and sensitivity of the model. The screening tool was correctly able to detect 7/10 MLS cases and 4/10 non-MLS cases. The model showed an accuracy of 55% with high specificity (70%) and moderate sensitivity of 40%. Conclusion: An automated solution for screening the MLS can prove useful for neurosurgeons. The results are strong evidence that 3D CNN can assist clinicians in screening MLS cases in an emergency setting.

PROTAC-Design-Evaluator (PRODE): An Advanced Method for In-Silico PROTAC Design.

PROTAC (proteolysis-targeting chimeras) is a rapidly evolving technology to target undruggable targets. The mechanism by which this happens is when a bifunctional molecule binds to a target protein and also brings an E3 ubiquitin ligase in proximity to trigger ubiquitination and degradation of the target protein. Yet, in-silico-driven approaches to design these heterobifunctional molecules that have the desired functional properties to induce proximity between the target protein and E3 ligase remain to be established. In this paper, we present a novel in-silico method for PROTAC design and to demonstrate the validity of our approach, we show that for a BRD4-VHL-PROTAC-mediated ternary complex known in the literature, we are able to reproduce the PROTAC binding mode, the structure of the ternary complex formed therein, and the free energy (ΔG) thermodynamics favoring ternary complexation through theoretical/computational methodologies. Further, we demonstrate the use of thermal titration molecule dynamics (TTMD) to differentiate the stability of PROTAC-mediated ternary complexes. We employ the proposed methodology to design a PROTAC for a new system of FGFR1-MDM2 to degrade the FGFR1 (fibroblast growth factor receptor 1) that is overexpressed in cancer. Our work presented here and named as PROTAC-Designer-Evaluator (PRODE) contributes to the growing literature of in-silico approaches to PROTAC design and evaluation by incorporating the latest in-silico methods and demonstrates advancement over previously published PROTAC in-silico literature.

Correlation between Transcranial Ultrasound and CT Head to Detect Clinically Significant Conditions in Post-craniectomy Patients Performed by Emergency Physician: A Pilot Study.

Background: The main objective is to detect clinically significant conditions by transcranial ultrasound (TCS) in post-decompressive craniectomy (DC) patients who come to the emergency department. Materials and methods: This was a cross-sectional observational study. We studied 40 post-DC patients. After primary stabilization, TCS was done. Computer tomography of head was done within 2 hours of performing TCS. The correlation between both modalities were assessed by the measurement of lateral ventricle (LV) (Bland-Altman plot), Midline shift and mass lesion. Additionally, normal cerebral anatomy, 3rd and 4th ventricles and external ventricular drainage (EVD) catheter visualization were also done. Results: About 14/40 patients came with non-neurosurgical complaints and 26/40 patients came with neurosurgical complaints. Patients with non-neurosurgical complaints (4/14) had mass lesions and 1/14 had MLS. Patients with neurosurgical complaints (11/26) had mass lesions and about 5 patients had MLS. A good correlation was found between TCS and CT of head in measuring LV right (CT head = 17.4 ± 13.8 mm and TCS = 17.1 ± 14.8 mm. The mean difference (95% CI) = [0.28 (-1.9 to 1.33), ICC 0.93 (0.88-0.96)], Left [CT head = 17.8 ± 14.4 mm and TCS = 17.1 ± 14.2 mm, the mean difference (95% CI) 0.63 (-1.8 to 0.61), ICC 0.96 (0.93-0.98)], MLS [CT head = 6.16 ± 3.59 (n = 7) and TCS = 7.883 ± 4.17 (n = 6)] and mass lesions (kappa 0.84 [0.72-0.89] [95% CI] p-value < 0.001). The agreement between both modalities for detecting mass lesions is 93.75%. Conclusion: Point of care ultrasound (POCUS) is a bedside, easily operable, non-radiation hazard and dynamic imaging tool that can be used for TCS as a supplement to CT head in post-DC patients in emergency as well as in ICU. However, assessment of the ventricular system (pre/post-EVD insertion), monitoring of regression/progression of mass lesion, etc. can be done with TCS. Repeated scans are possible in less time which can decrease the frequency of CT head. How to cite this article: Chouhan R, Sinha TP, Bhoi S, Kumar A, Agrawal D, Nayer J, et al. Correlation between Transcranial Ultrasound and CT Head to Detect Clinically Significant Conditions in Post-craniectomy Patients Performed by Emergency Physician: A Pilot Study. Indian J Crit Care Med 2024;28(3):299-306.

Quantifiable identification of flow-limited ventilator dyssynchrony with the deformed lung ventilator model.

BACKGROUND: Ventilator dyssynchrony (VD) can worsen lung injury and is challenging to detect and quantify due to the complex variability in the dyssynchronous breaths. While machine learning (ML) approaches are useful for automating VD detection from the ventilator waveform data, scalable severity quantification and its association with pathogenesis and ventilator mechanics remain challenging. OBJECTIVE: We develop a systematic framework to quantify pathophysiological features observed in ventilator waveform signals such that they can be used to create feature-based severity stratification of VD breaths. METHODS: A mathematical model was developed to represent the pressure and volume waveforms of individual breaths in a feature-based parametric form. Model estimates of respiratory effort strength were used to assess the severity of flow-limited (FL)-VD breaths compared to normal breaths. A total of 93,007 breath waveforms from 13 patients were analyzed. RESULTS: A novel model-defined continuous severity marker was developed and used to estimate breath phenotypes of FL-VD breaths. The phenotypes had a predictive accuracy of over 97% with respect to the previously developed ML-VD identification algorithm. To understand the incidence of FL-VD breaths and their association with the patient state, these phenotypes were further successfully correlated with ventilator-measured parameters and electronic health records. CONCLUSION: This work provides a computational pipeline to identify and quantify the severity of FL-VD breaths and paves the way for a large-scale study of VD causes and effects. This approach has direct application to clinical practice and in meaningful knowledge extraction from the ventilator waveform data.

Hospitals Should Offer Straws Only on Demand to the Public and Patients-An Environmental and Patient Care Imperative.

Plastic straws have become the poster child of waste associated with unnecessary single-use plastics. The visibility of straws littering the land and marine environments has influenced proposals to decrease the use of plastic straws. These include bans on plastic straws at the city, state, and national levels and by many corporations. However, most hospitals continue to use plastic straws in hospital dining areas and for patients. Hospital dining areas are like other public dining areas, so eliminating plastic straws should be straightforward. Regarding the use of straws by patients, we review evidence and propose that patients should not be routinely given straws. Instead, physicians and nursing staff should request straws depending on the patient's medical needs. Plastic straws make up only a tiny fraction of hospital waste but can be a catalyst to create awareness and decrease unnecessary plastic use in other areas of the hospital. Mitigating climate change requires a concerted effort from hospital leadership and healthcare providers. Only then will hospitals be able to fulfill their climate pledge of net zero emissions by 2050.

A Novel Method for Prediction of Raised Intracranial Pressure Through Automated ONSD and ETD Ratio Measurement From Ocular Ultrasound.

The paper presents a novel framework for the prediction of the raised Intracranial Pressure (ICP) from ocular ultrasound images of traumatic patients through automated measurement of Optic Nerve Sheath Diameter (ONSD) and Eyeball Transverse Diameter (ETD). The measurement of ONSD using an ocular ultrasound scan is non-invasive and correlates with the raised ICP. However, the existing studies suggested that the ONSD value alone is insufficient to indicate the ICP condition. Since the ONSD and ETD values may vary among patients belonging to different ethnicity/origins, there is a need for developing an independent global biomarker for predicting raised ICP condition. The proposed work develops an automated framework for the prediction of raised ICP by developing algorithms for the automated measurement of ONSD and ETD values. It is established that the ONSD and ETD ratio (OER) is a potential biomarker for ICP prediction independent of ethnicity and origin. The OER threshold value is determined by performing statistical analysis on the data of 57 trauma patients obtained from the AIIMS, New Delhi. The automated OER is computed and compared with the conventionally measured ICP by determining suitable correlation coefficients. It is found that there is a significant correlation of OER with ICP (r = .81, p ≤ .01), whereas the correlation of ONSD alone with ICP is relatively less (r = .69, p = .004). These correlation values indicate that OER is a better parameter for the prediction of ICP. Further, the threshold value of OER is found to be 0.21 for predicting raised ICP conditions in this study. Scatter plot and Heat map analysis of OER and corresponding ICP reveal that patients with OER ≥ 0.21, have ICP in the range of 17 to 35 mm Hg. In the data available for this research work, OER ranges from 0.17 to 0.35.

Automated intracranial hemorrhage detection in traumatic brain injury using 3D CNN.

Objectives: Intracranial hemorrhage (ICH) is a prevalent and potentially fatal consequence of traumatic brain injury (TBI). Timely identification of ICH is crucial to ensure timely intervention and to optimize better patient outcomes. However, the current methods for diagnosing ICH from head computed tomography (CT) scans require skilled personnel (Radiologists and/or Neurosurgeons) who may be unavailable in all centers, especially in rural areas. The aim of this study is to develop a neurotrauma screening tool for identifying ICH from head CT scans of TBI patients. Materials and Methods: We prospectively collected head CT scans from the Department of Neurosurgery, All India Institute of Medical Sciences, New Delhi. Approximately 738 consecutive head CT scans from patients enrolled in the department were collected for this study spanning a duration of 9 months, that is, January 2020 to September 2020. The metadata collected along with the head CT scans consisted of demographic and clinical details and the radiologist's report which was used as the gold standard. A deep learning-based 3D convolutional neural network (CNN) model was trained on the dataset. The pre-processing, hyperparameters, and augmentation were common for training the 3D CNN model whereas the training modules were set differently. The model was trained along with the save best model option and was monitored by validation metrics. The Institute Ethics Committee permission was taken before starting the study. Results: We developed a 3D CNN model for automatically detecting the ICH from head CT scans. The screening tool was tested in 20 cases and trained on 200 head CT scans, with 99 normal head CT and 101 CT scans with some type of ICH. The final model performed with 90% sensitivity, 70% specificity, and 80% accuracy. Conclusion: Our study reveals that the automated screening tool exhibits a commendable level of accuracy and sensitivity in detecting ICH from the head CT scans. The results indicate that the 3D CNN approach has a potential for further exploring the TBI-related pathologies.

Pathological Spectrum and ß-APP Immunoreactivity as a Diagnostic Tool of Diffuse Axonal Injury following Traumatic Brain Injury: A Novel Classification.

Aim Different deposition patterns and grading systems used to define and identify DAI remain discordant and to date these are a challenge in clinical practice. Our main objective was to study the post-mortem axonal changes and develop a grading system to identify DAI on the basis of histopathological and immunoreactive ß-amyloid precursor protein (ß-APP) observations in severe TBI cases. Methods Prospective study with 35 decedents with sTBI (GCS score ≤ 8) was conducted and samples were collected from three different sites-corpus callosum, thalamus and brain stem. Serial sections from each site were stained with hematoxylin and eosin (H&E), and immunohistochemistry (IHC) of ß-APP. Results We developed a grading system based on histopathological characteristics to assess the overall damage of axonal injury. We found maximum histopathological changes in cases with prolonged stay. Corpus callosum showed maximum changes in both gradings. Curiously, we also detected axonal swellings with H&E staining. Usually neglected, the thalamus also showed significant histopathological and immunoreactive changes for sTBI. Conclusion Our study based on histopathological and ß-APP scoring system to define and identify DAI thus facilitates accurate diagnosis of DAI post mortem, which has forensic implications, and may further contribute toward survival and improvement of quality of life of sTBI patients.

Identifying barriers and facilitators along the hepatitis C care cascade to inform human-centered design of contextualized treatment protocols for vulnerable populations in Austin, Texas: a qualitative study.

BACKGROUND: Hepatitis C virus (HCV) is a leading cause of liver-related mortality and morbidity. Despite effective direct acting antivirals and a simplified treatment algorithm, limited access to HCV treatment in vulnerable populations, including people experiencing homelessness (PEH) and people who inject drugs (PWID), hinders global elimination. Adapting the evidence-based, simplified HCV treatment algorithm to the organizational and contextual realities of non-traditional clinic settings serving vulnerable populations can help overcome specific barriers to HCV care. The first phase of the Erase Hep C study aimed to identify barriers and facilitators specific to these vulnerable populations to design the site-specific, simplified treatment protocols. METHODS: Forty-two semi-structured qualitative interviews, guided by the Practical, Robust Implementation and Sustainability Model (PRISM) framework, were conducted with clinic staff, community-based organizations providing screening and linkage to care, and patients diagnosed with HCV, to identify contextual barriers and facilitators to treatment at a local community health center's Health Care for the Homeless program in Austin, Texas. Audio-recorded interviews were systematically analyzed using thematic analysis informed by the PRISM framework and design thinking, to anchor barriers and facilitators along the HCV care cascade. Findings were fed into human-centered design workshops to co-design, with clinic staff, site-specific, simplified HCV treatment protocols. RESULTS: The specific needs of PEH and PWID patient populations informed barriers and facilitators of HCV care. Barriers included tracking patients who miss critical appointments or labs, medication access and adherence, and patient HCV knowledge. Clinical teams leveraged existing facilitators and incorporated solutions to barriers into clinic workflows to improve care coordination and medication access. Actionable solutions included augmenting existing staff roles, employing HCV care navigation throughout the cascade, and standardizing medication adherence counseling. CONCLUSIONS: Clinic staff identified HCV care facilitators to leverage, and designed actionable solutions to address barriers, to incorporate into site-specific treatment protocols to improve patient HCV outcomes. Methods used to incorporate staff and patient experiential knowledge into the design of contextualized treatment protocols in non-traditional clinic settings could serve as a model for future implementation research. The next phase of the study is protocol implementation and patient enrollment into a single-arm trial to achieve HCV cure.

Posterior pedicle inferior turbinate flap for recurrent cerebrospinal fluid leak following endoscopic transsphenoidal surgery.

BACKGROUND: Adequate reconstruction of skull base following endoscopic transsphenoidal surgery is the most crucial step in reducing postoperative morbidity and mortality. Although, the success rate of traditional nasoseptal flap is very high, specific surgical scenarios preclude its use. A variety of vascularised endonasal and tunnelled scalp flaps have been described in the literature to address such situations. Posterior pedicle inferior turbinate flap (PPITF) is one such locally available vascularised flap. METHODS: Two patients with recurrent CSF leak following endoscopic transsphenoidal resection of pituitary adenoma were included. The nasoseptal flap was not available in both patients due to previous surgery. Hence, a PPITF based on the posterolateral nasal artery, a branch of sphenopalatine artery, was harvested and used for skull base reconstruction. RESULTS: In both patients, CSF leak subsided in the immediate postoperative period. In one patient, sensorium improved and was subsequently discharged in stable condition. Other patient succumbed to meningitis in the postoperative period. CONCLUSIONS: The PPITF is a valuable alternative to the conventional nasoseptal flap when the latter is not available and it is very important for an endoscopic skull base surgeon to be familiar with the technique of harvesting and using the PPITF.

Alterations of oligodendrocyte progenitor cells (OPCs) with survival time in humans following high impact brain trauma.

BACKGROUND: As there is a lack of comprehensive literature regarding the molecular environment of the human brain emphasizing on oligodendrocyte progenitor cells (OPCs) following high impact brain trauma. The protagonist of OPCs post severe traumatic brain injury (sTBI) provides a significant thrust towards estimating time elapsed since trauma as well as developing novel therapeutic approaches. The present study was carried out to study post trauma alterations pertaining to myelin sheath and oligodendrocyte response with survival time. MATERIALS AND METHODS: In the present study, victims (both male and female) of sTBI (n = 64) were recruited and contrasted with age and gender matched controls (n = 12). Post mortem brain samples from corpus callosum and grey white matter interface were collected during autopsy examination. Extent of myelin degradation and response of OPC markers Olig-2 and PDGFR-α were evaluated using immunohistochemistry and qRT-PCR. STATA 14.0 statistical software was used for data analysis with P-value<0.05 considered statistically significant. RESULTS: Timewise qualitative correlation with extent of demyelination performed using LFB-PAS/IHC-MBP, IHC Olig-2 and mRNA expression revealed tendency towards remyelination in both corpus callosum and grey white matter interface. Number of Olig-2 positive cells was significantly higher in sTBI group as compared to control group (P-value: 0.0001). Moreover, mRNA expression studies of Olig-2 showed significant upregulation in sTBI patients. mRNA expression of Olig-2 and PDGFR-α in sTBI patients showed significant variation with respect to survival time (p value:0.0001). CONCLUSION: Detailed assessment of post TBI changes implementing various immunohistochemical and molecular techniques shall potentially reveal intriguing and important inferences in medicolegal practices and neurotherapeutics.