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© 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 licenseBackground: Traumatic brain injury (TBI) is increasingly recognised as being responsible for a substantial proportion of the global burden of disease. Neurosurgical interventions are an important aspect of care for patients with TBI, but there is little epidemiological data available on this patient population. We aimed to characterise differences in casemix, management, and mortality of patients receiving emergency neurosurgery for TBI across different levels of human development. Methods: We did a prospective observational cohort study of consecutive patients with TBI undergoing emergency neurosurgery, in a convenience sample of hospitals identified by open invitation, through international and regional scientific societies and meetings, individual contacts, and social media. Patients receiving emergency neurosurgery for TBI in each hospital's 30-day study period were all eligible for inclusion, with the exception of patients undergoing insertion of an intracranial pressure monitor only, ventriculostomy placement only, or a procedure for drainage of a chronic subdural haematoma. The primary outcome was mortality at 14 days postoperatively (or last point of observation if the patient was discharged before this time point). Countries were stratified according to their Human Development Index (HDI)—a composite of life expectancy, education, and income measures—into very high HDI, high HDI, medium HDI, and low HDI tiers. Mixed effects logistic regression was used to examine the effect of HDI on mortality while accounting for and quantifying between-hospital and between-country variation. Findings: Our study included 1635 records from 159 hospitals in 57 countries, collected between Nov 1, 2018, and Jan 31, 2020. 328 (20%) records were from countries in the very high HDI tier, 539 (33%) from countries in the high HDI tier, 614 (38%) from countries in the medium HDI tier, and 154 (9%) from countries in the low HDI tier. The median age was 35 years (IQR 24–51), with the oldest patients in the very high HDI tier (median 54 years, IQR 34–69) and the youngest in the low HDI tier (median 28 years, IQR 20–38). The most common procedures were elevation of a depressed skull fracture in the low HDI tier (69 [45%]), evacuation of a supratentorial extradural haematoma in the medium HDI tier (189 [31%]) and high HDI tier (173 [32%]), and evacuation of a supratentorial acute subdural haematoma in the very high HDI tier (155 [47%]). Median time from injury to surgery was 13 h (IQR 6–32). Overall mortality was 18% (299 of 1635). After adjustment for casemix, the odds of mortality were greater in the medium HDI tier (odds ratio [OR] 2·84, 95% CI 1·55–5·2) and high HDI tier (2·26, 1·23–4·15), but not the low HDI tier (1·66, 0·61–4·46), relative to the very high HDI tier. There was significant between-hospital variation in mortality (median OR 2·04, 95% CI 1·17–2·49). Interpretation: Patients receiving emergency neurosurgery for TBI differed considerably in their admission characteristics and management across human development settings. Level of human development was associated with mortality. Substantial opportunities to improve care globally were identified, including reducing delays to surgery. Between-hospital variation in mortality suggests changes at an institutional level could influence outcome and comparative effectiveness research could identify best practices. Funding: National Institute for Health Research Global Health Research Group.

Background: Human epidermal growth factor receptor 2 (Her2) gene located in human chromosome17, encodes Her2 tyrosine kinase protein, and is overexpressed in breast cancer cells. Her2 is activated on phosphorylation of tyrosine by adenosine triphosphate (ATP). Nonetheless, Her2 excessively partakes in the development and prognosis of specific types of aggressive breast cancers. Therefore, Her2 inhibition therapy is primary target for the treatment of aggressive breast cancer. At present, lapatinib is one of the Food and Drug Administration approved Her2 inhibitors used in cancer therapy. In molecular docking process, glabrene with slightly higher binding energy competitively bound to the active receptor site comparable to lapatinib and ATP. Therefore, glabrene could emerge as a potential candidate for restricting Her2 overexpressed breast cancer. Objective: The present study aimed to demonstrate the inhibitory activity of glabrene, an isoflavene and xenoestrogen found in liquorice root, along with known Her2 inhibitor, lapatinib. Methods: ATP, lapatinib, and glabrene were docked on human Her2 protein 3D structure which revealed glabrene as a competitive Her2 inhibitor akin to lapatinib. Results: The docking results suggested the binding site similarities of ATP, lapatinib, and glabrene. The binding energies of docked ATP, lapatinib, and glabrene complexes with Her2 were −9.1 kcal/mol, −10.5 kcal/mol, and −11.3 kcal/mol, respectively. Conclusion: The in silico docking simulation of ATP, lapatinib, and glabrene suggested that glabrene is likewise a competitive Her2 inhibitor.

Background. Human transmembrane protease 2 (TMPRSS2) protein is essential for priming spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in association with human angiotensin-converting enzyme 2 (ACE2) surface receptor to facilitate viral invasion into host human cell through ACE2 receptor. Impeding TMPRSS2 protein activity is currently a preferred choice of the treatment of coronavirus disease 2019 (COVID-19) which is caused by SARS-CoV-2. Curcumin and folic acid are potential candidates for inhibiting TMPRSS2. Objective. The present study aimed to demonstrate the inhibitory activities of curcumin and folic acid, along with known human serine protease inhibitors such as nafamostat and camostat, on TMPRSS2. Methods. Curcumin and folic acid, along with nafamostat and camostat, were docked on a modeled human TMPRSS2 protein 3D structure. Nafamostat and curcumin interactions with targeted TMPRSS2 protein were identical whereas camostat and folic acid displayed similar interactions. Results. The hydrogen bond (H-bond) energies of docked curcumin, folic acid, nafamostat, and camostat were −19.86 kJ/mol, −17.63 kJ/mol, −10.53 kJ/mol, and −14.41 kJ/mol, respectively. Higher H-bond energies could strengthen protein-ligand interactions. Our results showed binding site similarities between curcumin and nafamostat as well as folic acid and camostat. Conclusion. The current in silico simulation suggested that curcumin and folic acid displayed binding poses with TMPRSS2 which are similar to nafamostat and camostat. Therefore, curcumin and folic acid could emerge as potential drug candidates to control COVID-19.

Ventriculoperitoneal (VP) shunt is a frequently performed operation to achieve cerebrospinal fluid (CSF) diversion but is associated with many complications. Postoperative delayed intracerebral hemorrhage is a kind of rare but catastrophic complication of a VP shunt which questions the survival of a seemingly recovered patient. Here, we present one such case where the patient presented to casualty in altered sensorium and with a history of vomiting. On examination, the Glasgow Coma Scale (GCS) score was E2V1M3; pupils were middilated but reactive. Computerized tomography of the brain showed ventriculomegaly and hydrocephalus, and an emergency VP shunt was done. There was an initial phase of good recovery followed by sudden loss consciousness, vomiting, and a fall in the GCS scores on postoperative day 7. Computed tomography showed an intracerebral hematoma along the shunt track and an intraventricular bleed. The presumed cause for this occurrence is a deranged coagulation profile.

Basal ganglia bleed, though common in hypertensive, is unusual in posttraumatic patients. Bilateral basal ganglia hematoma following trauma is extremely rare and is limited to few case reports. The authors report three cases of bilateral basal ganglia hematomas in traumatic patients. All the cases were managed conservatively.

Background: Traumatic Intraventricular hemorrhage is commonly associated with other lesions like intracerebral contusions, subdural hemorrhage and subarachnoid hemorrhage. Isolated post- traumatic intraventricular hemorrhage is uncommon. It is mostly seen in the pediatric population and rarely seen in adults. Aims: To analyze the Demographics, mode of Injuries and outcome in injuries causing isolated post traumatic intraventricular hemorrhage which is a rare entity. Materials and Methods: This is a Retrospective analytic study of six cases, conducted at our Hospital in a span of eight years [2010-2018]. Results: Mean age of presentation is 36 years and all were males. The most common clinical presentation included loss of consciousness followed by vomiting and ENT bleed. Four cases presented with severe head injury and two with mild head injury as per Glasgow coma scale score. Mode of injury was acceleration and deceleration in all the cases. NCCT and CT Angiogram brain were done in all the cases which revealed isolated intraventricular hemorrhage without any vascular or tumoral pathology. All the patients were managed conservatively. Conclusion: The outcome was equivocal (3 patients had a bad outcome and 3 good outcomes) in our study.

Aims: The aim is to study the various factors associated with depressed skull fractures (DSFs) and their relationship with outcomes in patients who underwent surgery. Settings and Design: This was a cross-sectional study in a hospital setting. Patients and Methods: One hundred and fifty patients who underwent surgeries over a period of 6 years at our institute for DSFs were followed up and outcomes were analyzed. Patients having other medical- or trauma-related surgical morbidities were excluded. All age groups were studied. Statistical Analysis Used: The statistical analysis was performed using Chi-square test. Results: There was a significant relationship between the mode of injury, Glasgow coma scale (GCS) score at admission and discharge, and underlying brain injuries with the outcomes. The variables such as pneumocephalus, dural tears, type of fracture and site of the fracture, and age and sex distribution of the patient were not statistically influencing the outcomes. Conclusions: Patients who underwent surgery for DSFs, with good GCS at admission and discharge, with no underlying brain injury, and who did not sustain injuries in a road traffic accident had better outcomes.

Aim To assess and compare the clinical, radiological, and functional outcomes of anterolateral and posterolateral decompression and spinal stabilization in the thoracolumbar tuberculous spine. Material and methods 30 patients with thoracolumbar spinal tuberculosis were treated surgically between September 2014 and 2018. Fifteen patients underwent anterolateral decompression and spinal stabilization from September 2014 to September 2016. These patients were studied retrospectively (group A). Fifteen patients underwent posterolateral decompression by costotransversectomy and spinal stabilization from September 2016 to September 2017 were studied prospectively. Neurological recovery, correction of kyphotic deformity, pain (visual analog score) and ESR, and duration of stay were assessed. Neurological outcome was assessed using Frankel grading, and pain was assessed using visual analog scale. Results The average follow-up period in both the groups is 12 months. There was a statistically significant difference in the kyphotic angle correction between anterolateral and posterolateral groups at the end of 12 months (follow up). No statistically significant difference was found between the two groups for ESR, visual analog scale for pain, and neurological recovery (Frankel's grading) at the end of 12 months. Conclusion Both anterolateral and posterolateral approaches are sufficient thoracic and thoracolumbar tuberculous spine but, the posterolateral approach allows a significant correction of kyphotic angle, better improvement of pain and lesser duration of stay.

Introduction Fluorescein sodium is one of the fluorophores that is used in the resection of intracranial lesions. It is commonly used along with a customized microscope, which is expensive and not available universally. In this study, we describe a simple, inexpensive method for better visualization of intracranial and spinal cord lesions with fluorescein. Materials and Methods After a test dose, 20 mg/kg of fluorescein sodium was administered intravenously at the time of intubation. A blue light source was used before resection for precise localization of the intracranial lesions after durotomy. Most of the resection was done under the white light, while the blue light was used intermittently to delineate the pathologic tissue from the normal tissue and to ensure safe maximal resection. The intensity of fluorescein staining under white light and blue light was noted. Results The study comprised 40 cases of gliomas, meningiomas, abscesses, spinal cord tumors, and cerebellopontine angle lesions. Thirty-five lesions showed good fluorescence under the blue light, which helped us achieve better resection of the pathologic lesions. Conclusions Fluorescein sodium is a safe dye; it can be used to aid in precise localization and safe maximal resection of the pathologic tissue with the help of a blue light source at any center with challenged resources. The blue light enhances the fluorescence and visualization of the pathologic tissue, and this technique can be adopted by any surgeon without much difficulty even with a basic neurosurgical setup.

Epidermoid cysts are commonly seen intracranial lesions but their occurrence in the spine is rare. They account for

Extradural hemorrhages are commonly seen in coup head injuries, rarely seen in contrecoup head injuries. Acute extradural hemorrhage in the coup head injuries associated with a fracture is common, but the incidence of acute contrecoup extradural hemorrhage not associated with the fracture is extremely rare. Only 21 cases have been reported previously. A 28-year-old male patient presented to the emergency department with complaints of sustaining injuries in a road traffic accident by fall from a two-wheeler. No history of loss of consciousness, vomiting, seizures, and ear/nose bleed. On examination, the patient was conscious and coherent with a Glasgow Coma Scale score of 15/15 and a laceration on the right frontotemporal region which was sutured. Contrast tomography of the brain revealed an extradural hemorrhage of 10 mm thickness in the left parieto-occipital region with soft tissue swelling in the right temporoparietal region, without any evident fractures in the calvarium. The patient was managed conservatively. Contrecoup extradural hematoma is a rare entity, and those without fracture are extremely rare. Early diagnosis, careful observation, and management lead to a good outcome.

An epidural hematoma is a life-threatening condition which necessitates early surgical intervention. Conservative management is undertaken in smaller hematomas; rarely, a massive hematoma may show spontaneous resolution which can be picked up only by a repeat computed tomography before surgery. Here, we report one such case where we noted a surprisingly rapid resolution of an epidural hematoma, which was relatively a large clot and where the last minute call to have a repeated computed tomography scan changed the line of management altogether from a surgical one to conservative. The patient in this particular case is a 20-year-old male, with a history of fall from height. The initial scan showed a large epidural hematoma which requires surgical evacuation, whereas the subsequent scans showed near-complete resolution and hence was managed conservatively. Rare cases like these should always be kept in mind, and the importance of a repeat scan should never be disregarded.

Aim: This is a prospective study to analyze the clinical, radiological, and functional outcomes of posterolateral decompression and spinal stabilization with pedicle screws and rods done for the thoracolumbar tuberculous spine. Materials and Methods: This study was conducted at Gandhi Medical College and Hospital from September 2016 to September 2017 on 30 patients who underwent posterolateral decompression and spinal stabilization using pedicle screw and rod fixation for active spinal tuberculosis. Pain, erythrocyte sedimentation rate (ESR), kyphotic angle correction, and Frankel's grading were taken to study the clinical, radiological, and functional outcome at the end of 1 year. Other parameters taken into consideration were the duration of stay and level of involvement; antituberculous therapy was given to all the patients for 16–18 months until the signs of radiological healing were evident. Results: This study comprised of 30 patients with a mean age of presentation of 39.835 ± 14.75 and M: F ratio of 1:1. The mean duration of stay is 10.67 ± 4.06, and the most common level of involvement is D6–D11. Kyphotic angle was corrected by a mean of 19.08 ± 5.44 at the end of 1 year (P < 0.001). Visual analog score improved from a median of 8 preoperatively to 2 at follow-up (P < 0.001). ESR improved from a mean of 37.08 ± 12.64 mm/h preoperatively to 19.83 ± 13.68 mm/h at follow-up (P = 0.01). There was an improvement in Frankel's grading in most of the patients at the end of 12 months. Radiological healing was evident in the form of the reappearance of trabeculae formation and bony fusion at the end of 12 months. Conclusion: Posterolateral approach is a good method for decompression and spinal stabilization because of significant kyphotic correction, improvement in pain, good neurological recovery, less duration of stay, and less morbidity.

Janus kinase 2 (JAK2) is a prospective drug target for myeloproliferative neoplasms, mainly polycythemia Vera, essential thrombocythemia and primary myelofibrosis disorders...

Coenzyme Q10 (CoQ10) (1) is lipid-soluble and an important mitochondrial redox component, endogenously produced antioxidant in the human organisms. CoQ10 (1) plays an important role in the production of cellular energy, strengthens the immune system and acts as a free radical scavenger. Aging, poor eating habits, infections and stress affect the amounts of CoQ10 (1) in the humans. As human beings age, they begin to lose the ability to synthesize CoQ10 (1) from food resulting in its deficiency. CoQ10 (1) facilitates the production of adenosine triphosphate (ATP) in the mitochondria by participating in redox reactions within the electron transport chain. Cardiovascular disease deaths in elders are 80% in males and 75% in females. The average age of death from cardiovascular diseases in the developing world is 68 years and in developed world it is 80 years. Cardiovascular disease onset is 7-10 years earlier in men as compared to women. A low level of myocardial CoQ10 (1) is related to the severity of heart failure. Long-term CoQ10 (1) treatment of patients with chronic heart failure is safe and reduces major adverse cardiovascular complications.

Craniofacial epidermoid cysts are rare tumors representing 0.2%–1% of all the intracranial tumors. Intradiploic variants account for 25% of these cysts. These cysts are benign, slow-growing, congenital tumors derived from ectodermal remnants misplaced during embryogenesis. Mean age at presentation of these lesions is 40 years; epidermoid cysts are typically asymptomatic (Toglia JU, Netsky MG, Alexander E Jr. Epithelial (epidermoid) tumors of the cranium. Their common nature and pathogenesis. J Neurosurg 1965;23:384-93). Giant extradural epidermoid cysts with profound deformation of the brain and extensive lytic skull lesions may allow a normal life without any significant neurological deficits. Computed tomography scan and magnetic resonance imaging play an important role in the diagnosis of the lesion and management protocol. Histologically, epidermoid cysts are lined by stratified squamous epithelium and are filled with anucleatic keratin (Hao S, Tang J, Wu Z, Zhang L, Zhang J, Wang Z. Natural malignant transformation of an intracranial epidermoid cyst. J Formos Med Assoc 2010;109:390-6). Complete removal of the cyst along with its capsule is the treatment of choice. Recurrences of intradiploic epidermoid cyst have been reported. Here, we report a case of 14-year-old girl presenting with a giant frontal intradiploic epidermoid cyst with an intracranial and extracranial extension without any neurological deficits. Bifrontal craniotomy was performed and cyst was excised in toto.

Closed Reduction Technique and Stabilization of Traumatic Fracture Dislocation L5-S1 Traumatic fracture dislocation and spondyloptosis L5-S1 is a rare injury. It indicates fatal trauma associated with other injuries. In many occasions these injuries missed in initial examination and hence many of the cases reported were operated late. We report a case of L5-S1 spondyloptosis diagnosed and operated in acute stage. Reduction has been achieved with closed manipulation and later patient had 360° stabilization in stages. Closed reduction achieved by exaggerating the angulation followed by distraction in line of angulation and reduction of dislocation by pelvic rotation.

Cerebellopontine Angle Neurenteric Cyst – A Case Report and Review of Literature A case of neurenteric cyst at CP Angle discussed. Only few intracranial neurenteric cyst have been reported. Around 60 cases were reported. Most of the intracranial lesions were in the posterior fossa. Around twenty cases of Neurenteric cysts in the CP angle were reported. The present case is a neurenteric cyst in the CP angle belongs to Odom’s group A lined by single layer of columnar cell with PAS positive intracellular deposits. The clinical presentation, pathology and management are discussed here with review of literature.

High-grade spondylolysthesis and spondyloptosis management have various options. There were no large series reported to support any particular treatment modality. The aim of surgery is to get solid bony fusion to get relief of instability and its symptoms as well as relief of neurological symptoms. There are many treatment options which are associated with technical difficulties and high incidence of complications and failures. In situ transsacral fibular graft with posterolateral fusion along with posterior decompression is a good surgical option. It offers anterior and posterolateral fusion for instability pain and relief of neurological symptoms in most of the patients. It is technically simple, with no major surgery-related complications.The cases of high-grade spondylolysthesis operated since 2008 with one year minimal follow up were included in this study. Six cases were operated during this period. All were females in their second and third decade of life. All of them had transsacral fibular grafting with posterolateral fusion and decompression. One of the cases had additional anterior procedure with sacral widening with bone graft. The clinical status and bony fusion has been assessed at the end of one year after surgery and also for assessing final outcome.All the patients had solid bony fusion with no progression of slip and are pain free and relived of neurological symptoms. conclusions: In situ transsacral fibular graft with posterolateral fusion and posterior decompression is technically simple surgical option with minimal risks and reliable outcome.

We report a rare condition in a child where the skull fracture was associated with prolapse of orbital contents into anterior cranial fossa. CT scan findings are very much pathognomonic. This patient was operated, orbital contents have been relocated and orbital roof was reconstructed, but vision could not be restored.

Fourteen new withanolides 1-14, named withalongolides A-N, respectively, were isolated from the aerial parts of Physalis longifolia together with eight known compounds (15-22). The structures of compounds 1-14 were elucidated through spectroscopic techniques and chemical methods. In addition, the structures of withanolides 1, 2, 3, and 6 were confirmed by X-ray crystallographic analysis. Using a MTS viability assays, eight withanolides (1, 2, 3, 7, 8, 15, 16, and 19) and four acetylated derivatives (1a, 1b, 2a, and 2b) showed potent cytotoxicity against human head and neck squamous cell carcinoma (JMAR and MDA-1986), melanoma (B16F10 and SKMEL-28), and normal fetal fibroblast (MRC-5) cells with IC50 values in the range between 0.067 and 9.3 μM.

Despite development of current targeted therapies for medullary thyroid cancer (MTC), long-term survival remains unchanged. Recently isolated novel withanolide compounds from Solanaceae physalis are highly potent against MTCs. We hypothesize that these withanolides uniquely inhibit RET phosphorylation and the mammalian target of rapamycin (mTOR) pathway in MTC cells as a mechanism of antiproliferation and apoptosis.MTC cells were treated with novel withanolides and MTC-targeted drugs. In vitro studies assessed cell viability and proliferation (MTS; trypan blue assays), apoptosis (flow cytometry with Annexin V/PI staining; confirmed by Western blot analysis), long-term cytotoxic effects (clonogenic assay), and suppression of key regulatory proteins such as RET, Akt, and mTOR (by Western blot analysis).The novel withanolides potently reduced MTC cell viability (half maximal inhibitory concentration [IC(50)], 270-2,850 nmol/L; 250-1,380 nmol/L for vandetanib; 360-1,640 nmol/L for cabozantinib) with induction of apoptosis at1,000 nmol/L of drug. Unique from other targeted therapies, withanolides suppressed RET and Akt phosphorylation and protein expression (in a concentration- and time-dependent manner) as well as mTOR activity and translational activity of 4E-BP1 and protein synthesis mediated by p70S6kinase activation at IC(50) concentrations.Novel withanolides from Physalis selectively and potently inhibit MTC cells in vitro. Unlike other MTC-targeted therapies, these compounds uniquely inhibit both RET kinase activity and the Akt/mTOR prosurvival pathway. Further translational studies are warranted to evaluate their clinical potential.

This is a retrospective study aimed to analyse the clinical outcomes of patients following anterior cervical decompression and fusion for radiculopathy in worker's compensation, third party and non-compensable group. The outcome of 224 cases operated be tween 1991 to 1998 were analysed. Only patients with radiculopathy due to a cervical disc protrusion and spondylosis were included. There were 140 non-compensable patients, 58 worker's compensation and 26 third party. There was no statistical difference in radiological fusion between the three groups ( P = 0.46). The worker's compensation and third party claimant groups, had an 'excellent' outcome at 65% and 69% respectively, compared to the non-compensation group at 79% ( P = 0.042). Rates of poor outcome were high in the worker's compensation group (9%) compared with third party (4%) and the non-compensable group (5%). Financial incentives seem to significantly influence the outcome of cervical disc surgery in our patient population.

BACKGROUND Intradiploic hematoma of the skull was first reported in 1934. The pathogenesis of this lesion is unclear. It is a very rare benign reactive process occurring after minor head trauma, with only seven cases reported in the literature to date. CASE DESCRIPTION A 3-year-old right hand dominant male presented with a non-tender parietal scalp swelling of a 1-year duration. History included a skull fracture located in the same region 24 months before presentation. Neurological examination was unremarkable. Pathological examination after curettage of the lesion revealed features consistent with organizing hematoma. CONCLUSIONS The pathology of chronic diploic hematoma mimics aneurysmal bone cyst, giant cell tumor, giant cell reparative granuloma, fibrous dysplasia, eosinophilic granuloma, intradiploic epidermoid and dermoid cyst, cavernous hemangioma, circumscribed osteomyelitis, and tuberculous granuloma. Chronic diploic hematoma is a lesion that must be differentiated from various skull lesions both radiologically and histologically as it is amenable to treatment with a complete cure once excised.