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Objective: The present study is a scoping review of the progress of the field of stem cell research (SCR) in Pakistan in the last two decades. Methods: Data was extracted from electronic search engines, international clinical trial registry platforms, and PubMed and presented in tabular and graphical form. Results: China, India and Iran are investing heavily in SCR. In Pakistan, reasonable growth in terms of the number of publications is observed in this area, however, clinical translation of the field does not demonstrate any considerable progress. The Government of Pakistan has developed the regulatory framework and initiated preliminary policymaking, adopting rules from international regulatory agencies like World Health Organization (WHO) and Federal Drug Authority (FDA), however, further clarity and policymaking are needed to address the growing trend of stem cell tourism in the country. Continued...

Objective: To explore the differences in demographic, surgical, and prognostic characteristics between the two genders in patients with brain tumours in Pakistan. Methods: This study was a retrospective cross-sectional analysis of patients with a histopathological brain tumour diagnosis across 32 high-volume hospitals in Pakistan. The study period was from January 1, 2019, to December 31, 2019. There were no restrictions on inclusion apart from time. Results: From 2750 patients enrolled in the study, 1605 (58.4%) were male, and 1142 (41.6%) were female . The median age amongst males was 36 (24-49), while the median age amongst females was 37 (24-48). The ratio of married to unmarried patients was 2.7:1 for females and 1.3:1 for males. Surgical treatment was carried out for 1430 (58.1%) males and 1013 (41.9%) females. The median time to surgery was 25 (4-107) days for males and 31 (5-98) days for females. The greatest disparity in tumour malignancy was in grade IV gliomas. Conclusion: Males generally have a higher incidence of brain tumours in our experience, apart from meningiomas, which favour females. The mortality rate and glioblastoma incidence rate are both higher amongst males. However, post-treatment cure is also witnessed. Sociocultural norms play a prominent role in accessing healthcare. Women are generally at a disadvantage compared to their male counterparts, which may impact reporting of brain tumour cases and treatment outcomes. Keywords: Brain neoplasms, Epidemiology, Gender equity, Retrospective study. Continue....

Objective: To enumerate the burden of ependymoma in our region and identify the demographic, tumoural, surgical, clinical characteristics, and outcomes of patients diagnosed with ependymoma. Methods: This retrospective cross-sectional study included patients admitted under neurosurgical service between January 1 and December 31, 2019. The inclusion criterion for the study was a histopathological diagnosis of the brain lesion. The experience of the ependymal brain tumours observed at the 32 participating sites in Pakistan is presented. Results: A total of 2750 patients with brain tumours were seen in 2019 at our centres of whom 58(2.1%) had a histopathological diagnosis of ependymoma. The median age at diagnosis was nine (IQR= 4.5-24.5) years. The median time to surgery from date of radiological diagnosis was 38.5 (IQR= 4-93.8) days. The median KPS score at presentation was 70 (IQR= 60-80), and post-surgery was 90 (IQR= 70-100), showing an average increase of 20. Our population's overall mortality rate for ependymoma was 31.1%, with the 30-day mortality rate being 2.2% (lower than the 4.5% on average for all brain tumours in our cohort). Conclusion: Ependymomas were predominantly found in the paediatric population in the presented cohort. While gender distribution and histopathological grading seemed to follow international trends, this study had a much higher mortality rate and a much lower gross total resection rate than centres in high-income countries. Keywords: Ependymoma, Brain neoplasm, Retrospective study, Epidemiology, LMIC. Continue...

Objective: To observe the patient characteristics and centres providing neuro-oncological care in public and private health hospitals in Pakistan. Methods: The Pakistan Association of Neuro-oncology carried out a retrospective, cross-sectional study in 2019 on patients admitted to 32 hospitals in Pakistan, with dedicated neurosurgical facilities. Patients with a histopathological diagnosis of an intracranial tumour were included. Results: Public health care facilities catered for 84% patients with ages between 20 and 60 years and children having intracranial tumours. Private centres were utilised by 66.7% patients from the upper socioeconomic sector. More patients were lost to follow-up in the public sector (n = 784) versus in the private sector (n = 356). Mortality was also higher in the public sector hospitals, (13.9%) as compared to 9.6% in the private sector. Conclusion: Public and private sector health services for neuro-oncological care in Pakistan still have a long way to go to cover the gaps for unmet needs. Strengthening health systems for brain tumour care is imperative to increase both the access to care and the quality of care to fulfil this need. Keywords: Retrospective study, Health systems, Brain neoplasms, Health care, Epidemiology, Chemoradiotherapy.

Objective: To identify the surgical incidence and prevalence of schwannoma in our region and quantify the demographic, surgical, neoplastic, and outcome characteristics of the patients diagnosed with schwannoma. Methods: A retrospective cross-sectional study was conducted from January 1 to December 31, 2019. Enrolled were 32 of the highest volume neurosurgical centres in Pakistan. Patients with a histopathological diagnosis of schwannoma and radiological imaging were included in the study. Medical records were reviewed for data, and SPSS version 25 was used for statistical analysis. Patients were followed up for one year, which was the duration of the study. Results: From 2750 patients diagnosed with brain tumours, 148 patients had schwannomas. Out of these, 84 (56.8%) patients were male, and 64 (43.2%) patients were female. The mean age of the patients was 39 ± 14 years. The socioeconomic statuses of the enrolled patients were lower in 72 (53.3%) patients, middle in 57 (42.2%) patients, and upper middle to upper in 6 (4.4%) patients. All patients underwent surgery, 14 patients received radiotherapy, and two patients received chemotherapy. In our cohort, 115 (77.7%) patients presented to public sector hospitals, with only 33 (22.3%) patients presenting to private hospitals. At the end of the study period, 60 (40.5%) patients had been lost to follow-up. Of the remaining 88 patients, 75 (85.2%) were alive. The mortality rate on a one-year follow-up was 14.8%. Conclusion: Schwannoma comprises a larger percentage of the brain tumours in our regions than reported in the literature. The high mortality rate is of particular concern and warrants further investigation to improve patient care and outcomes. Keywords: Schwannoma, Brain neoplasm, Retrospective study, Epidemiology, LMIC Continue...

Objective: To build a comprehensive brain tumour database that will allow us to analyse in detail the prevalence, demographics, and outcomes of the disease in paediatric, adolescent, and young adult age groups. Method: A national cross-sectional study was conducted at 32 centres, and data regarding patient demographics and brain tumours were collected. This data was then stratified based on age groups, healthcare sectors, socioeconomic status, tumour types, and surgical outcomes. Result: Most of the patients who were diagnosed with brain tumours belonged to a lower socioeconomic background and went to public sector hospitals. More males were diagnosed with and treated for brain tumours in the paediatric, adolescent, and young adult populations. The most common tumour in the paediatric population was medulloblastoma (23.7%) and the most common tumour in the adolescent (27.8%) and young adult population (34.7%) was glioma. Significant improvement in KPS scores were seen for: craniopharyngioma (p = 0.001), meningioma (p < 0.0005) and pituitary adenoma (p < 0.0005) Conclusion: This study shows that in all three age groups, there was a greater prevalence in males. Most of the patients belonged to a lower-middle-income class background and most patients presented to public sector hospitals. Greater knowledge of these parameters unique to each age group is the key to understanding and alleviating the burden of disease. Cancer registries, specifically brain tumour registries that keep up-to-date records of these patients, are essential to identify and keep track of these unique parameters to advance medical research and treatment strategies, ultimately lowering the disease burden. Keywords: Pediatric, Neuro-oncology, Adolescent and young adult, AYA, Medulloblastoma, Craniopharyngioma, Epidemiology.

Objective: To combat the lack of brain tumour registries, the Pakistan Brain Tumour Epidemiology Study (PBTES) was conducted without any funding from an external source. Methods: A retrospective analysis of patient data, including patients of all age groups diagnosed with all histopathological types of brain tumours from all over Pakistan, was performed. For this, Pakistan Brain Tumour Consortium (PBTC) was established, including 32 neurosurgical centres from around the country. Data was collected online through a proforma that included variables such as patient demographics, clinical characteristics, operative details, postoperative complications, survival indices, and current functional status. The data collection and analysis team included principal investigators, core leads, regional leads, regional associates, and student facilitators. Despite logistical concerns and lack of resources, the PBTES was conducted successfully, and a formal brain tumour surveillance database was formed without any external funding, which remains unheard of. Conclusion: The methods applied in this study are reproducible and can be employed not just to develop more robust brain tumour and other cancer registries but also to study the epidemiology of communicable and non-communicable diseases in resource-limited settings, both locally and globally. Keywords: brain neoplasms, retrospective study, epidemiology, noncommunicable diseases. Continue...

Objective: To examine the effect of distance travelled for brain tumour surgery on patient outcomes in an LMIC. Methods: Data were collected as part of the Pakistan Brain Tumour Epidemiology Study (PBTES) for brain tumour patients who underwent surgery in 2019. Mapping software was used to calculate the distance travelled by each patient from their primary address to the hospital. This was analysed in correlation with outcomes (change in KPS score, current status) and demographic variables. Results: Of 2366 patients, the median distance travelled across the country was 104 km (IQR: 9.07 - 304). Only 970 (41%) patients had access to brain tumour surgical care within 50 km of their primary address. A total of 372 (15.7%) patients requiring brain tumour surgery had to travel more than 500 km to reach their primary care hospital. Patients travelling more than 50 km for brain tumour surgery had better pre- and post-surgery Karnofsky performance scores (p

Objective: To define the landscape of treatment patterns and current epidemiological data regarding gliomas in Pakistan. Methods: As part of the Pakistan Brain Tumour Epidemiology Study (PBTES), data were collected from 32 neurosurgical centres across the country. Our retrospective study looked at patients who underwent surgical procedures for gliomas in 2019 in neurosurgical centres. The data was collated and analysed using STATA version 15. Results: A total of 781 patients with gliomas were identified 479(61.8%) in public sector hospitals, 302(39.1%) in the private sector). The most common histopathological subtypes were glioblastoma 262 (33.5%), followed by astrocytoma 147(18.8%) and oligodendroglioma 93(11.9%). Gender distribution was skewed towards men 508(65%). Private institution hospitals performed surgical biopsies as the first surgical procedure 75(23%) more often than public hospitals 38(9%). Chemotherapy was given to 115(29.8%) patients, and there was no data regarding 467(53%) of patients. Similarly, only 202(43.9%) patients received radiation therapy, and there was no data for 469(60%) of patients. For high-grade gliomas specifically, only 95(31.8%) patients with HGG have a record of receiving radiation therapy, and only 57(18.9%) had a record of being started on chemotherapy. Conclusions: Our study highlighted gaps in glioma management within Pakistan, with only around half of our patients receiving chemotherapy and radiotherapy, despite it being indicated. In our experience, high-grade tumours were diagnosed at a younger age than in high-income countries, but overall, glioblastoma was a smaller constituent of our tumour sample than expected. Keywords: Glioblastoma. Oligodendroglioma, Glioma, Astrocytoma, Brain Neoplasms, Registries, Epidemiology. Continue...

Objective: To quantify the frequency of craniopharyngiomas presenting to tertiary care neurosurgical centres, the demographics and mortality rate, and commonly presenting to neurosurgical practice. Methods: Our study was a retrospective cross-sectional analysis of patients admitted at 32 neurosurgical centres between January 1, 2019, and December 31, 2019, with brain tumour. Kruskal Wallis analysis was used to determine normality; normally distributed variables were reported as means with standard deviation, while median with interquartile range was used for non-normally distributed variables. Results: Of 2750 patients with brain tumours, 114 patients presented with craniopharyngioma. The median age at diagnosis was 18 years, with 42 (42.8%) patients below the age of 15, 40 (40.9%) patients aged 15-39, and 16 (16.3%) patients aged 40 and above. There were 70 (61.4%) males and 44 (38.6%) females in our cohort. Gross total resection was performed in 42(36.8%), 45 (39.5%) underwent subtotal resection, 9 (7.9%) underwent CSF diversion only, and 2 (1.8%) had a biopsy. Most of our patients 94(82.5%) presented to public hospitals, with 20 (17.5%) patients presenting to private hospitals (p=0.002). The overall survival at two years was 86.8% in patients with known outcomes, and only 10% of patients died within 30 days of surgery. Conclusion: Craniopharyngiomas comprised a small portion of all brain tumours in our region. They are more common in males and in patients from the lower socioeconomic class. These patients mainly presented to public sector hospitals, and the three highest volume centres were all public sector institutions. The overall survival rate at two years in our region is lower than in other regions. Keywords: Craniopharyngioma, Brain neoplasm, Retrospective study, Epidemiology, LMIC. Continue...

Objective: To investigate waiting times for brain tumour surgery in Pakistan from a nationwide sample and highlight specific affected patient populations. Methods: A nationwide study was conducted as part of the Pakistan Brain Tumour Epidemiology Study; data from 32 high-volume neurosurgical centres were collected. The national sample included 2,750 patients. Time to surgery was calculated by the difference in dates recorded for radiological diagnosis and the date of the first surgery. This was further stratified according to demographic factors, histopathological diagnosis, type of surgical procedure performed and survival outcomes. Results: The data of 1,474 patients for time to surgery was available. Patients travelling to public hospitals had significantly longer mean wait times (94.07 (CI: 85.29, 102.84) vs 75.14 (CI: 54.72, 95.56) days, p

Due to the differences in size and invasiveness when compared to non-giant macroadenomas (nGPAs), giant pituitary adenomas (GPAs) are considerably harder to resect. This study aimed to differentiate GPAs from nGPAs, based on the presenting complaints, surgical approaches, peri- and postoperative outcomes.We retrospectively analyzed cases of pituitary macroadenomas that underwent surgical resection at a tertiary care hospital. GPAs were tumors greater than 4 cm in the largest dimension, while nGPAs were tumors smaller than 4 cm. 55 GPA patients and 70 nGPA patients from 2006 to 2017 were included. Demographic, perioperative, and post-operative outcomes were evaluated. Group comparisons for continuous variables were made using an independent t-test/Mann Whitney U test and categorical data was analyzed on Chi-square/Fisher exact test; a p-value of 0.05 was considered significant.Visual deterioration was the most common complaint, reported by 61.4% of nGPA patients and 81.8% of GPA patients. The mean extent of gross total resection was 47.1% in nGPA patients and 18.2% in GPA patients (p = 0.001). After surgery, tumor recurrence was seen in 1.4% of nGPA patients and 18.2% of GPA patients (p = 0.001). First re-do surgery was required in 5.7% of nGPA patients and 25.5% of GPA patients (p = 0.004).Compared to nGPAs, GPAs are more likely to present with a higher number of preoperative symptoms, and lesser chances of gross total tumor resection. GPAs are also associated with a higher rate of recurrence, which results in more follow-up procedures. Larger, multi-center longitudinal studies need to be done to validate these findings.

The objective of this systematic review is to determine the fate of spinal implants when patients develop postoperative wound infection after posterior instrumental fusion in a degenerative spine.A systematic review of the English-language literature (published between January 2001 and July 2020) was undertaken to identify articles documenting the management strategy for surgical site infections (SSIs) after posterior lumbar spinal fusion. Studies on pedicle screw fixation after trauma, immunocompromised, metastatic spine disease, and combined anterior/posterior approach were excluded. Two independent reviewers assessed the level of evidence quality using the criteria set by the North American Spine Society, and disagreements were resolved by consensus.Of the 3071 citations identified, 49 met the criteria to undergo full-text review. Outcomes after SSIs were studied from a combined pool of 1150 patients who had undergone instrumental spinal fusion. The collected data showed that 456 patients (39.97%) had undergone spinal implant removal after SSI while 694 patients (60.03%) had their implants retained until the resolution of SSI. There was an absolute risk reduction (ARR) of 29% (-0.292) and a relative risk reduction (RRR) of 50.3% (-0.503) of implant removal if the patient underwent wound debridement following SSI. The number needed to treat (NNT) for wound debridement was calculated at 3.31 from our pooled cohort. The ARR in implant removal following vacuum-assisted closure (VAC) therapy was 16.6% and RRR was noted at 40.4%. This led to a high value of NNT at 6.0 patients. There was an ARR of 33.5% and a RRR of 70.7% was estimated in patients undergoing continuous irrigation.Our review of the literature suggests that surgeons prefer early wound debridement with or without negative pressure wound therapy under antimicrobial coverage for eradication of SSI after posterior lumbar spinal fusion. Implant removal is generally reserved for cases refractory to the other treatment modalities.

Redundant Nerve Roots (RNR) is a common radiological observation of elongated tortuous appearance of cauda equina nerve roots in sagittal MRI. It is considered a poor prognostic factor, but the associated spinal morphometry remains unfamiliar.A retrospective cohort study was conducted at the Aga Khan University Hospital, Pakistan. Patients, aged 18 or above, undergoing decompressive spinal surgery due to degenerative Lumbar Spinal Canal Stenosis (LSCS) in 2015 were included. Patients were divided in groups as per presence of RNR and assessed for spinal morphometric parameters.Fifty-two patients, aged 57.52 ± 12.08 years, were enrolled in the study. The patients in RNR group were older than those in non-RNR group (p = 0.023). RNR was significantly associated with sedimentation sign (15 vs 11; p = 0.011), as well as L2/L3 (12 vs 9; p = 0.043) and L3/L4 (18 vs 18; p = 0.034) stenosis. Ligamentum flavum hypertrophy at the most stenotic level was more common in the RNR group (20 vs 19; p = 0.006). The only quantitative parameter statistically associated with RNR was lower ligamentous interfacet distance (5.07 ± 1.95 vs 8.07 ± 4.26 mm; p = 0.010). All other parameters did not contribute to the development of RNR in LSCS patients. The multivariate model revealed significant contribution of age, male sex, ligamentous interfacet distance and disc bulge to develop RNR.Certain spinal morphometric parameters contribute towards RNR formation, which represents higher degree of spinal stenosis. These parameters, along with RNR, should be regularly reported for preoperative consideration of LSCS management.

Introduction This study translated and validated the Urdu version of the European Organization for Research and Treatment of Cancer Quality of Life (QoL) Questionnaire (EORTC QLQ-C30) and Brain Module (QLQ-BN20) amongst patients with primary brain tumors (PBT) in Pakistan, and assessed the correlation of QoL with resilience, depression, and anxiety. Methods Translation of the EORTC QLQ-C30 and QLQ-BN20 was performed as per EORTC guidelines. A survey comprising of Urdu translations of EORTC QLQ-C30, QLQ-BN20, Wagnild and Young Resilience Scale (RS-14) and Hospital Anxiety and Depression Scale was administered to patients with PBT at a tertiary care hospital in Pakistan. Reliability (via Cronbach alpha), content validity index (CVI) scores, construct validity, and inter-scale correlations were assessed. Results Our sample consisted of 250 patients with PBT, most commonly glioma (46.8%) and meningioma (21.2%). All patients were able to understand the Urdu translations. The Cronbach alphas for the QLQ-C30 and the QLQ-BN20 were 0.860 and 0.880, respectively. The CVI scores for clarity and relevance were high for both the EORTC QLQ-C30 (0.98 and 0.96, respectively) and the QLQ-BN20 tool (0.81 and 0.95, respectively). The global QoL domain (EORTC QLQ-C30) showed significant positive correlations with resilience (r = 0.422), and significant negative correlations with depression (r = − 0.541) and anxiety (r = − 0.502). Strong inter-scale correlations were observed between physical functioning and insomnia (r = − 0.690) and role functioning and insomnia (r = − 0.641). Conclusion Our study confirms the Urdu versions of the EORTC QLQ-C30 and QLQ-BN20 as valid clinical tools for the measurement of QoL in primary brain tumors patients within the cultural and socioeconomic context of Pakistan. Supplementary Information The online version contains supplementary material available at 10.1186/s41687-021-00354-6., Plain language summary Quality of life (QoL) is an important facet of well-being for patients with primary brain tumors (PBTs), as these individuals face significant distress during the course of their illness and treatment. It is important to have valid and reliable tools to accurately measure the QoL of patients with PBTs. The EORTC QLQ-C30 (European Organization for Research and Treatment of Cancer Quality of Life Questionnaire) and its brain tumor-specific module EORTC QLQ-BN20 (EORTC QLQ-Brain Neoplasms 20) are exactly that. However, the use of the EORTC QLQ-C30 and QLQ-BN20 is limited in Pakistan, where the national language is Urdu, and the majority of patients are of low socioeconomic backgrounds. Since no Urdu translations of the EORTC QLQ-C30 and QLQ-BN20 exist, we aimed to translate and validate these tools to enable their applicability in Pakistan. The Urdu versions of the EORTC QLQ-C30 and QLQ-BN20 demonstrated good validity amongst patients with PBTs. Thus, our study confirms the EORTC QLQ-C30 and QLQ-BN20 as valuable clinical tools for the measurement of QoL in primary brain tumors patients within the linguistic, cultural and socioeconomic context of Pakistan. Supplementary Information The online version contains supplementary material available at 10.1186/s41687-021-00354-6.

Epidemiological studies have significantly helped determine the burden, types, and geographical distribution of brain tumours in HICs (highincome countries). However, brain tumour data from low-and-middle-income countries is often sparse, focusing on a few centres1. The situation in Pakistan is no different. Few oncological registries exist in our region that focus on common tumours. Collecting data regarding brain tumours has been challenging, as evidenced by the underreported incidence of brain tumours by centers such as the Karachi Cancer Registry (KCR), Pakistan Atomic Energy Commission (PAEC) report, and GLOBOCAN. Brain tumours are distinct from other cancer types by having more than 200 subtypes, requiring complex analysis, grading, and personalized therapeutic strategies. Moreover, there is no current standardized system to record brain tumour patient data, making it difficult to collate data from various centers. Continue.

Low- and middle-income countries sustain the majority of pediatric cancer burden, with significantly poorer survival rates compared to high-income countries. Collaboration between institutions in low- and middle-income countries and high-income countries is one of the ways to improve cancer outcomes.Patient characteristics and effects of a pediatric neuro-oncology twinning program between the Hospital for Sick Children in Toronto, Canada and several hospitals in Karachi, Pakistan over 7 years are described in this article.A total of 460 patients were included in the study. The most common primary central nervous system tumors were low-grade gliomas (26.7%), followed by medulloblastomas (18%), high-grade gliomas (15%), ependymomas (11%), and craniopharyngiomas (11.7%). Changes to the proposed management plans were made in consultation with expert physicians from the Hospital for Sick Children in Toronto, Canada. On average, 24% of the discussed cases required a change in the original management plan over the course of the twinning program. However, a decreasing trend in change in management plans was observed, from 36% during the first 3.5 years to 16% in the last 3 years. This program also led to the launch of a national pediatric neuro-oncology telemedicine program in Pakistan.Multidisciplinary and collaborative efforts by experts from across the world have aided in the correct diagnosis and treatment of children with brain tumors and helped establish local treatment protocols. This experience may be a model for other low- and middle-income countries that are planning on creating similar programs.

In the fifteenth century, trained individuals called' barber surgeons' mastered the art of handling sharp instruments and performing basic surgical procedures. They even founded a 'United Company of Barber Surgeons' in 1540.1 Besides shaving and haircutting, they were trained to perform dental extractions and a few surgical procedures. Later in 1745, qualified doctors and surgeons came together and founded 'Company of Surgeons' in the UK, which later became the Royal College of Surgeons inLondon.2 This progression from anecdotal experiences of the guild of barbers to a formal society that helped the implementation of scientifically reasoned decisions by Royal College Surgeons was only possible because surgeons were able to appreciate the value of the evidence and incorporate it into their practices. Continuous...

Non-functioning pituitary adenomas account for 30% of anterior pituitary tumours. Based on their inability to secrete hormones, these are often diagnosed incidentally or due to pressure symptoms. Understanding the pathogenesis of these adenomas can provide insight into factors leading to its progression and serving as biomarkers for early recognition. A literature search was performed in the current narrative review for articles published in PubMed for the last 10 years till January 2020 on micro-ribonucleic acid involved in the pathogenesis of non-functioning pituitary adenomas. Of the 478 articles found, 21(4.4%) were filtered. In total, 106 micro-ribonucleic acids were identified, 25(23.5%) of which appeared in more than one study. Among them, 7(28%)were up-regulated, 11(44%) down-regulated, and 7(28%) were either up- or down-regulated. Micro- ribonucleic acids allow the screening, diagnosis and treatment of diseases in a relatively easy and inexpensive manner. This can revolutionise tumour management in the years ahead, especially in resource-constrained low- and middle-income countries.

Traumatic brain injury (TBI) refers to any insult to the brain resulting in primary (direct) and secondary (indirect) damage to the brain parenchyma. Secondary damage is often linked to the molecular mechanisms that occur post TBI and result in excitotoxicity, neuroinflammation and cytokine damage, oxidative damage, and eventual cell death as prominent mechanisms of cell damage. We present a review highlighting the relation of each of these mechanisms with TBI, their mode of damaging brain tissue, and therapeutic correlation. We also mention the long-term sequelae and their pathophysiology in relation to TBI focusing on Parkinson disease, Alzheimer disease, epilepsy, and chronic traumatic encephalopathy. Understanding of the molecular mechanisms is important in order to realize the secondary and long-term sequelae that follow primary TBI and to devise targeted therapy for quick recovery accordingly.

Background The COVID‐19 pandemic has created a need to prioritize care because of limitation of resources. Owing to the heterogeneity and high prevalence of breast cancers, the need to prioritize care in this vulnerable population is essential. While various medical societies have published recommendations to manage breast disease during the COVID‐19 pandemic, most are focused on the Western world and do not necessarily address the challenges of a resource‐limited setting. Aim In this article, we describe our institutional approach for prioritizing care for patients presenting with breast disease. Methods and results The breast disease management guidelines were developed and approved with the expertise of the Multidisciplinary Breast Program Leadership Committee (BPLC) of the Aga Khan University, Karachi, Pakistan. These guidelines were inspired, adapted, and modified keeping in view the needs of our resource‐limited healthcare system. These recommendations are also congruent with the ethical guidelines developed by the Center of Biomedical Ethics and Culture (CBEC) at the Sindh Institute of Urology and Transplantation (SIUT), Karachi. Our institutional recommendations outline a framework to triage patients based on the urgency of care, scheduling conflicts, and tumor board recommendations, optimizing healthcare workers' schedules, operating room reallocation, and protocols. We also describe the “Virtual Blended Clinics”, a resource‐friendly means of conducting virtual clinics and a comprehensive plan for transitioning back into the post‐COVID routine. Conclusion Our institutional experience may be considered as a guide during the COVID‐19 pandemic, particularly for triaging care in a resource‐limited setting; however, these are not meant to be universally applicable, and individual cases must be tailored based on physicians' clinical judgment to provide the best quality care.

Background: External ventricular drains (EVD) are commonly utilized for temporary diversion of cerebrospinal fluid (CSF). Many neurosurgeons prefer long-tunneled EVDs in their routine practice. However, it is still unclear whether this extended tunneling helps in reducing CSF infection. Keeping this in mind, we decided to compare infection rates in long-tunneled versus short-tunneled EVDs in the setting of a developing country. Materials and Methods: A prospective study of 60 patients was conducted. Consenting patients who underwent short-tunneled (Group A) or long-tunneled (Group B) EVDs between January 2008 and June 2009 were followed during the course of their inpatient care. All operational protocol was standardized during the trial. Serial samples of CSF were analyzed to detect infection. Results: Mean age of patients was 33.6 years with 32 males (53.3%). Mean duration of long-tunneled EVD was 13.4 ± 7.2 days, whereas that of short-tunneled EVD was 5.3 ± 2.7 days (P < 0.001). Three patients with long-tunneled EVD (10.0%), whereas one patient with short-tunneled EVD (3.3%) developed drain-related infections; however, this was non-significant (P = 0.301). However, patients with short-tunneled EVD got infected earlier on day 3when compared with the long-tunneled EVDs, which got infected after a mean duration of 7.3 days. The overall risk of infection for long-tunneled EVDs was 7.46 per 1,000 ventricular drainage days which was comparable to the risk of 6.33 per 1,000 ventricular drainage days seen for short-tunneled EVDs. Conclusion: Long-tunneled EVDs appear to only delay potential infections without having any effect on the actual risk of infection. Long-tunneled EVD in a resource-limited setting is technically challenging and may not yield additional benefits to the patient. However, larger and prospective studies are needed to establish the rate of infections and other complications.

Fungal infections of the central nervous system (CNS) are uncommon. Despite several advancements in diagnosis and treatment of these infections, the mortality rates remain high. The current retrospective study was planned to define the demographic and clinical features of patients with CNS fungal infections. Conducted at Aga Khan University Hospital, Karachi, and comprising CNS fungal infections operated between January 2000 and December 2015. The study analysed whether a short course of pre-operative anti-fungal therapy may improve outcomes in these patients. There were 47 cases confirmed on histopathology and/or microbiology. Outcome measures used were Glasgow coma score (GCS), Glasgow outcome score (GOS) and Karnofsky performance score (KPS). The overall 30-day mortality was 20(42.5%). Fungal infections of the CNS can occur in both immune-compromised and immune-competent patients. Early diagnosis, radical surgery, pre-operative anti-fungal therapy for at least 2 weeks, pre- and postoperative Voriconazole therapy results in more favourable outcomes.

Cranial reconstruction after decompressive craniectomy (DC) has been shown to be associated with a relatively high complication rate (16.4%-34%) compared with standard neurosurgical procedures (2%-5%). Most studies that have previously attempted to formulate a multivariate model for identifying factors predictive of postoperative complications of cranioplasty either were unsuccessful or yielded conflicting results. Therefore, fuzzy logic-based fuzzy inference system (FIS), which has proven to be a useful tool for risk prediction in medical and surgical conditions, was used in this study to identify predictors of complications of cranioplasty.A retrospective chart review of all the patients who underwent DC followed by elective cranioplasty at Aga Khan University Hospital, during a 10-year period (2000-2010), was carried out to collect data on 24 carefully selected preoperative variables or inputs. The proposed FIS had 24 inputs, 3 outputs, and a set of 7 fuzzy-based rules. All inputs were assigned degrees of membership, and complications were further divided into "severe," "minor," and "least" output classes with each of them representing 2 membership functions: "less" and "more." For each set of inputs, a specific portion of the hypersurface was masked out. The centroid of this subsurface represented the defuzzified output corresponding to 1 percentage value for each output. The maximum of these outputs for each of the 3 output classes was selected to be the final output class. Each output class was compared to the actual outcome of patients, and positive predictive value, negative predictive value, sensitivity, and specificity of FIS for predicting complications were calculated.A total of 89 patients (mean [SD] age, 33.1 [15.0] y; male-to-female ratio, 3:1) were included in the study. The common postoperative complications included seizures (14.6%), cerebrospinal fluid leak (4.5%), neurologic deficits (3.4%), hydrocephalus (3.4%), superficial wound infection (3.4%), and osteomyelitis (2.2%). The FIS correctly identified all 7 patients who developed severe complications after cranioplasty (true positives) and all 82 patients who did not develop severe complications (true negatives). Thus, the FIS has a sensitivity and specificity of 100% in predicting severe complications.Our study shows that the procedure of cranioplasty is associated with a high complication rate and that FIS has a 100% sensitivity and specificity in predicting severe complications after cranioplasty. It will prove to be an invaluable tool for clinicians once the results are validated by a similar prospective study with a larger sample size.

Objective To analyze the output and quality of neurosurgical research published from Pakistan in indexed peer reviewed journals. Methods Indexed peer reviewed publications from 2003 to 2008 were searched for neurosurgical contributions from Pakistan. The retrieved articles were evaluated to analyze the trends of publication and quality of evidence. Results Sixty-two neurosurgical research papers (10.3 per year, range 8–13) were published from Pakistan during the study period. Twenty-four (38.7%) publications were the contribution of just four primary authors; 25 (45.3%) of the publications were original research articles and 30 (48.4%) were either case reports or case series; and 38 (61.3%) of all the publications were from just three institutions in the country. Majority of publications were pertaining to neurooncology ( n =23, 37.1%) and neurosurgical trauma ( n =16, 25.8%). Overall, 48 (77.4%) papers were published in local indexed journals and only 14 (22.6%) in international journals. There were no basic science studies, and no papers offering level 1 or 2 evidence were published during the study period. Conclusion Neurosurgical research in Pakistan over the past six years has been unsatisfactory, both in terms of number and quality of publications. Analysis of six year publications also did not show any significant improvement in research trends.

Penetrating brain injury (PBI), though less prevalent than closed head trauma, carries a worse prognosis. The publication of Guidelines for the Management of Penetrating Brain Injury in 2001, attempted to standardize the management of PBI. This paper provides a precise and updated account of the medical and surgical management of these unique injuries which still present a significant challenge to practicing neurosurgeons worldwide. The management algorithms presented in this document are based on Guidelines for the Management of Penetrating Brain Injury and the recommendations are from literature published after 2001. Optimum management of PBI requires adequate comprehension of mechanism and pathophysiology of injury. Based on current evidence, we recommend computed tomography scanning as the neuroradiologic modality of choice for PBI patients. Cerebral angiography is recommended in patients with PBI, where there is a high suspicion of vascular injury. It is still debatable whether craniectomy or craniotomy is the best approach in PBI patients. The recent trend is toward a less aggressive debridement of deep-seated bone and missile fragments and a more aggressive antibiotic prophylaxis in an effort to improve outcomes. Cerebrospinal fluid (CSF) leaks are common in PBI patients and surgical correction is recommended for those which do not close spontaneously or are refractory to CSF diversion through a ventricular or lumbar drain. The risk of post-traumatic epilepsy after PBI is high, and therefore, the use of prophylactic anticonvulsants is recommended. Advanced age, suicide attempts, associated coagulopathy, Glasgow coma scale score of 3 with bilaterally fixed and dilated pupils, and high initial intracranial pressure have been correlated with worse outcomes in PBI patients.

Alzheimer's disease (AD) is a neurodegenerative disease. There are a limited number of therapeutic options available for the treatment of AD. Curcuminoids (a mixture of bisdemethoxycurcumin, demethoxycurcumin and curcumin) is the main chemical constituent found in turmeric, a well known curry spice, having potential in the treatment of AD. The objective of this study was to investigate the effects of curcuminoid mixture and individual constituents on spatial learning and memory in an amyloid-beta (Abeta) peptide-infused rat model of AD and on the expression of PSD-95, synaptophysin and camkIV. Curcuminoid mixture showed a memory-enhancing effect in rats displaying AD-like neuronal loss only at 30 mg/kg, whereas individual components were effective at 3-30 mg/kg. A shorter duration treatment with test compounds showed that the curcuminoid mixture and bisdemethoxycurcumin increased PSD-95 expression in the hippocampus at 3-30 mg/kg, with maximum effect at a lower dose (3 mg/kg) with respective values of 470.5 and 587.9%. However, after a longer duration treatment, two other compounds (demethoxycurcumin and curcumin) also increased PSD-95 to 331.7 and 226.2% respectively at 30 mg/kg. When studied for their effect on synaptophysin in the hippocampus after the longer duration treatment, the curcuminoid mixture and all three individual constituents increased synaptophysin expression. Of these, demethoxycurcumin was the most effective showing a 350.1% increase (P

Background Despite a lot of research into patient selection, a significant number of patients fail to benefit from surgery for symptomatic lumbar disk herniation. We have used Fuzzy Logic-based fuzzy inference system (FIS) for identifying patients unlikely to improve after disk surgery and explored FIS as a tool for surgical outcome prediction. Methods Data of 501 patients were retrospectively reviewed for 54 independent variables. Sixteen variables were short-listed based on heuristics and were further classified into memberships with degrees of membership within each. A set of 11 rules was formed, and the rule base used individual membership degrees and their values mapped from the membership functions to perform Boolean Logical inference for a particular set of inputs. For each rule, a decision bar was generated that, when combined with the other rules in a similar way, constituted a decision surface. The FIS decisions were then based on calculating the centroid for the resulting decision surfaces and thresholding of actual centroid values. The results of FIS were then compared with eventual postoperative patient outcomes based on clinical follow-ups at 6 months to evaluate FIS as a predictor of poor outcome. Results Fuzzy inference system has a sensitivity of 88% and specificity of 86% in the prediction of patients most likely to have poor outcome after lumbosacral miscrodiskectomy. The test thus has a positive predictive value of 0.36 and a negative predictive value of 0.98. Conclusion Fuzzy inference system is a sensitive method of predicting patients who will fail to improve with surgical intervention.

Objective:: The purpose of this retrospective review of all operated cases of pituitary adenomas in the last decade, is to define the demographic patterns and characteristics of such tumors and to assess surgical outcomes with regards to safety and efficacy of trans–sphenoidal tumor removal in our institution.Methods:Surgically treated pituitary adenomas presenting from 1995 till 2005 were reviewed for different variables. Results were expressed as mean, standard deviation and median for continuous and number with percentage for categorical data. Chi square test was applied to measure differences and significance was taken at p value < 0.05.Results:One hundred and twenty–five patients were operated for pituitary adenoma. Sixty–three percent were male and mean age was 37 years. Sixty percent of the patients presented with headache and/or visual symptoms. Twelve percent presented with pituitary apoplexy and 28% presented with symptoms due to pituitary hyperfunction. Fifty–five percent of patients had functioning and 44% had nonfunctioning adenomas. Mean pre operative tumor diameter from 86 pre op MRI scans was 26.76 mm (3–78 mm). Eighty–four percent of patients underwent trans–sphenoidal tumor resection and three percent had craniotomy. Mean size of post op residual tumor as calculated from 76 available post operative scans was 5.3 mm (range 0–31 mm). 17.6% of the patients required hormone replacement beyond three months and 10% were re–operated. Overall mortality was 1.6%.Conclusion:In Pakistan, patients are more likely to present either with apoplexy or with a giant pituitary adenoma than patients reported from developed countries. Overall, our results have been satisfactory and comparable with the literature.