An international, prospective observational study on traumatic brain injury epidemiology study protocol: GEO-TBI: Incidence.

Background: The epidemiology of traumatic brain injury (TBI) is unclear - it is estimated to affect 27-69 million individuals yearly with the bulk of the TBI burden in low-to-middle income countries (LMICs). Research has highlighted significant between-hospital variability in TBI outcomes following emergency surgery, but the overall incidence and epidemiology of TBI remains unclear. To address this need, we established the Global Epidemiology and Outcomes following Traumatic Brain Injury (GEO-TBI) registry, enabling recording of all TBI cases requiring admission irrespective of surgical treatment. Objective: The GEO-TBI: Incidence study aims to describe TBI epidemiology and outcomes according to development indices, and to highlight best practices to facilitate further comparative research. Design: Multi-centre, international, registry-based, prospective cohort study. Subjects: Any unit managing TBI and participating in the GEO-TBI registry will be eligible to join the study. Each unit will select a 90-day study period. All TBI patients meeting the registry inclusion criteria (neurosurgical/ICU admission or neurosurgical operation) during the selected study period will be included in the GEO-TBI: Incidence. Methods: All units will form a study team, that will gain local approval, identify eligible patients and input data. Data will be collected via the secure registry platform and validated after collection. Identifiers may be collected if required for local utility in accordance with the GEO-TBI protocol. Data: Data related to initial presentation, interventions and short-term outcomes will be collected in line with the GEO-TBI core dataset, developed following consensus from an iterative survey and feedback process. Patient demographics, injury details, timing and nature of interventions and post-injury care will be collected alongside associated complications. The primary outcome measures for the study will be the Glasgow Outcome at Discharge Scale (GODS) and 14-day mortality. Secondary outcome measures will be mortality and extended Glasgow Outcome Scale (GOSE) at the most recent follow-up timepoint.

Traumatic brain injury (TBI) is a significant global health problem, which affects 27­69 million people every year. After-effects of TBI commonly affect the injured individuals for years. Most patients who sustain a TBI are from developing countries. Research has shown that there are differences in patients' recovery after TBI between countries and hospitals. The causes of these differences are unclear and tackling them could improve TBI treatment worldwide. To address this need, we have recently established the Global Epidemiology and Outcomes Following Traumatic Brain Injury (GEO-TBI) registry. The international collaborative registry aims to collect data related to the causes, treatments and outcomes related to TBI patients. This data will hopefully enable future research to elucidate the causes of the recovery differences between hospitals, which could lead to improved patient outcomes. The GEO-TBI: Incidence study collects data from all TBI patients that are admitted to participating hospitals or undergo a neurosurgical operation due to TBI during a 90-day period. This study looks at the patient's recovery at discharge using the Glasgow Outcome at Discharge Scale (GODS), and at the 2-week mortality. In addition, the study also evaluates recovery at the most recent follow-up timepoint. We hope that this information will enhance our understanding on the causes, treatments, and commonness of TBI. The study results will also help local hospitals compare their treatment results to an international standard.

Current state of global neurosurgery activity amongst European neurosurgeons.

BACKGROUND: The expanding field of global neurosurgery calls for a committed neurosurgical community to advocate for universal access to timely, safe, and affordable neurosurgical care for everyone, everywhere. This study aims to (i) assess the current state of global neurosurgery activity amongst European neurosurgeons and (ii) identify barriers to involvement in global neurosurgery initiatives. METHODS: Cross-sectional study through dissemination of a web-based survey, from September 2019 to January 2020, to collect data from European neurosurgeons at various career stages. Descriptive analysis was conducted on respondent data. RESULTS: Three hundred and ten neurosurgeons from 40 European countries responded. 53.5% regularly follow global neurosurgery developments. 29.4% had travelled abroad with a global neurosurgery collaborative, with 23.2% planning a future trip. Respondents from high income European countries predominantly travelled to Africa (41.6%) or Asia (34.4%), whereas, respondents from middle income European countries frequently traversed Europe (63.2%) and North America (47.4). Cost implications (66.5%) were the most common barrier to global neurosurgery activity, followed by interference with current practice (45.8%), family duties (35.2%), difficulties obtaining humanitarian leave (27.7%) and lack of international partners (27.4%). 86.8% would incorporate a global neurosurgery period within training programmes. CONCLUSIONS: European neurosurgeons are interested in engaging in global neurosurgery partnerships, and several sustainable programmes focused on local capacity building, education and research have been established over the last decade. However, individual and system barriers to engagement persist. We provide insight into these to allow development of tailored mechanisms to overcome such barriers, enabling European neurosurgeons to advocate for the Global Surgery 2030 goals.

Are Hindfoot Procedures More Painful than Forefoot Procedures? A Prospective Observational Study in Elective Foot and Ankle Surgery.

Pain after lower limb orthopedic surgery can be severe. Poorly controlled pain is associated with adverse outcomes. Peripheral nerve blocks (PNB) have become popular in foot and ankle surgery for their effective pain control and low complication rates. It has always been assumed that hindfoot procedures are more painful than midfoot/forefoot procedures often requiring inpatient stay for pain relief. There are no published studies evaluating this assumption. To investigate whether hindfoot procedures are more painful than forefoot/midfoot procedures by measuring pain scores, assessing effectiveness of PNBs and patient satisfaction. One hundred forty patients undergoing elective foot and ankle surgery were prospectively studied. Inclusion criteria: Adults undergoing elective foot and ankle surgery. Exclusion criteria: Patients 16 years or under, those with alternate sources of pain, peripheral neuropathy, known substance abuse, psychiatric illness and incomplete pain scores. Pain was measured via the Visual Analog Scale at 3 time intervals: immediately, 6 hours and at 24 hours postoperatively. Analysis was via t-test. A p value of <.05 demonstrated a statistical significance. Forefoot/midfoot versus hindfoot surgery pain scores showed that there was no significant difference at any postoperative interval. PNB versus no PNB pain scores showed there was no significant difference, except at 24 hours postoperatively (p value .024). Patients who had a PNB experienced rebound pain at 24 hours. Hindfoot surgery is not more painful than forefoot/midfoot surgery. Patients who had a PNB experienced rebound pain at 24 hours postoperatively, a finding that requires further research.

Sexual Health Dysfunction After Radiotherapy for Gynecological Cancer: Role of Physical Rehabilitation Including Pelvic Floor Muscle Training.

INTRODUCTION: The present study aims to describe: 1. How the side effects of radiotherapy (RT) could impact sexual health in women; 2. The effectiveness of physical rehabilitation including pelvic floor muscle training (PFMT) in the management of sexual dysfunction after RT. MATERIALS AND METHODS: Search keys on PubMed, Web of Science, Scopus, PEDro, and Cochrane were used to identify studies on women treated with radical or adjuvant RT and/or brachytherapy for gynecological cancers with an emphasis on vulvo-vaginal toxicities and PFMT studies on sexual dysfunction for this group of women. RESULTS: Regarding the first key question, we analyzed 19 studies including a total of 2,739 women who reported vaginal dryness, stenosis, and pain as the most common side effects. Reports of dosimetric risk factors and dose-effect data for vaginal and vulvar post-RT toxicities are scant. Only five studies, including three randomized controlled trials (RCTs), were found to report the effect of PFMT alone or in combination with other treatments. The results showed some evidence for the effect of training modalities including PFMT, but to date, there is insufficient evidence from high-quality studies to draw any conclusion of a possible effect. CONCLUSIONS: Gynecological toxicities after RT are common, and their management is challenging. The few data available for a rehabilitative approach on post-actinic vulvo-vaginal side effects are encouraging. Large and well-designed RCTs with the long-term follow-up that investigate the effect of PFMT on vulvo-vaginal tissues and pelvic floor muscle function are needed to provide further guidance for clinical management.

Global Surgery: A 30-Year Bibliometric Analysis (1987-2017).

INTRODUCTION: There has been a growing interest in addressing the surgical disease burden in low- and middle-income countries (LMICs). Assessing the current state of global surgery research activity is an important step in identifying gaps in knowledge and directing research efforts towards important unaddressed issues. The aim of this bibliometric analysis was to identify trends in the publication of global surgical research over the last 30 years. METHODS: Scopus® was searched for global surgical publications (1987-2017). Results were hand-screened, and data were collected for included articles. Bibliometric data were extracted from Scopus® and Journal Citation Reports. Country-level economic and population data were obtained from the World Bank. Descriptive statistics were used to summarise data and identify significant trends. RESULTS: A total of 1623 articles were identified. The volume of scientific production on global surgery increased from 14 publications in 1987 to 149 in 2017. Similarly, the number of articles published open access increased from four in 1987 to 68 in 2017. Observational studies accounted for 88.7% of the included studies. The three most common specialties were obstetrics and gynaecology 260 (16.0%), general surgery 256 (15.8%), and paediatric surgery 196 (12.1%). Over two times as many authors were affiliated to an LMIC institution than to a high-income country (HIC) institution (6628, 71.5% vs 2481, 28.5%, P < 0.001). A total of 965 studies (59.5%) were conducted entirely by LMIC authors, and 534 (32.9%) by collaborations between HICs and LMICs. CONCLUSION: The quantity of research in global surgery has substantially increased over the past 30 years. Authors from LMICs seemed the most proactive in addressing the global surgical disease burden. Increasing the funding for interventional studies, and therefore the quality of evidence in surgery, has the potential for greater impact for patients in LMICs.

Endoscopic skull base neurosurgical practice in the United Kingdom.

Background: Endoscopic skull base surgery (ESBS) is a new subspecialty area that has become more popular over the past 20 years. It is fast evolving and the indications are getting increasingly diverse. The skill-sets also continue to significantly improve, hence, we, the authors aim to assess the current status of this unique sub-specialty within the United Kingdom. Objective: Our objectives included identifying the proportion of neurosurgeons within the United Kingdom who utilize endoscopic skull base approaches, the background training involved and how much of the overall neurosurgical workload is constituted by endoscopic skull base neurosurgery. There was also a focus on the technical nuances involved with ESBS. Materials and methods: 45 neurosurgeons were included in this study, and a 47% response rate (n = 21) was obtained. Results: 7 (33%) had training in ESBS during residency and 8 (38%) had some fellowship exposure to ESBS. Each respondent did an average of 1.9 endoscopic skull base courses prior to commencing their practice. The length of practice ranged from 3 to 15 years (mean - 7.2 years). Although most of the surgeons had mixed sub-specialty interests, the most commonly associated sub-specialty with ESBS was lateral skull base surgery (38%). Conclusion: In the United Kingdom, ESBS appears to be commonly combined with a lateral/open skull base neurosurgical practice. Most of the surgeons had their ESBS training after formal residency. Collaboration with ENT occurs more commonly for extended transphenoidal procedures.

Time to surgery following chronic subdural hematoma: post hoc analysis of a prospective cohort study.

BACKGROUND: Chronic subdural hematoma (CSDH) is a common neurological condition; surgical evacuation is the mainstay of treatment for symptomatic patients. No clear evidence exists regarding the impact of timing of surgery on outcomes. We investigated factors influencing time to surgery and its impact on outcomes of interest. METHODS: Patients with CSDH who underwent burr-hole craniostomy were included. This is a subset of data from a prospective observational study conducted in the UK. Logistic mixed modelling was performed to examine the factors influencing time to surgery. The impact of time to surgery on discharge modified Rankin Scale (mRS), complications, recurrence, length of stay and survival was investigated with multivariable logistic regression analysis. RESULTS: 656 patients were included. Time to surgery ranged from 0 to 44 days (median 1, IQR 1-3). Older age, more favorable mRS on admission, high preoperative Glasgow Coma Scale score, use of antiplatelet medications, comorbidities and bilateral hematomas were associated with increased time to surgery. Time to surgery showed a significant positive association with length of stay; it was not associated with outcome, complication rate, reoperation rate, or survival on multivariable analysis. There was a trend for patients with time to surgery of ≥7 days to have lower odds of favorable outcome at discharge (p=0.061). CONCLUSIONS: This study provides evidence that time to surgery does not substantially impact on outcomes following CSDH. However, increasing time to surgery is associated with increasing length of stay. These results should not encourage delaying operations for patients when they are clinically indicated.

Predictive Factors of Spine Surgery Complications at a Major Government Hospital in Cambodia.

BACKGROUND: Spine pathology is a common reason for admission to neurosurgical units in low- and middle-income countries (LMICs) and can have high morbidity rates from lack of specialized institutes. However, good surgical outcomes and quality-of-life scores have been reported in LMICs. This study details the complication rates and predictive factors from spine surgery at a large hospital in Cambodia, aiming to identify high-risk patients to improve surgeon understanding of these complications for improved pre-operative planning and patient counseling. METHODS: This is a retrospective review of patients admitted for spine conditions to Preah Kossamak Hospital in Phnom Penh, Cambodia (2013-2017). Univariate analysis was conducted on potential predictive factors; variables with P < 0.1 were entered into multivariate logistic regression models. RESULTS: Seven hundred seventy-three patients were included. Forty-six patients had complications including wrong level surgery, hardware failure, and infection. On multivariate analysis, patients from the provinces of Kratie (P = 0.009) or Sihanoukville (P = 0.036), and those that delayed seeking care for more than 1 year after injury (P = 0.027), were significant predictive factors of postoperative complications, and American Spinal Injury Association grade A injury (P = 0.020) was a predictive factor of poor outcome. CONCLUSIONS: Many factors play a role in spine surgery complications in LMICs, including limited access to intra-operative technology, low follow-up rates, and minimal physiotherapy and rehabilitation capabilities. Patients with long delays in presentation, American Spinal Injury Association grade A injuries, and lumbar-level surgery may be especially susceptible to complications and postoperative morbidity. Despite this, institutions have reported encouraging spine trauma outcomes, and spine surgeries are becoming more accepted and safe operations in many LMICs.

Evaluating the Effectiveness and the Impact of Donated Neurosurgical Equipment on Neurosurgical Units in Low- and Middle-Income Countries: The World Federation of Neurosurgical Societies Experience.

BACKGROUND: Surgical practice highly depends on the availability of surgical equipment; this is particularly relevant to low- and middle-income countries (LMICs), where resources are limited. A key part of the efforts to improve surgical provision globally include providing affordable equipment to LMICs; however, the effectiveness and the impact of these initiatives have not yet been assessed. We aimed to evaluate the World Federation of Neurosurgical Societies neurosurgical equipment program in this context. METHODS: Recipients were identified from the World Federation of Neurosurgical Societies records; contact details were gathered. An online survey was used to collect data on equipment, including its current use, any malfunctioning issues, suitability, reliability, serviceability, and the impact it has had on the unit. RESULTS: Responses were received from 16 units, totaling 28 pieces of equipment. A total of 75% of the equipment is still in use; of this, 57% is fully functioning, and 43% is used despite some malfunction. We found that 25% of the equipment is broken and unusable; high-maintenance items, such as high-speed drills, feature in this category (100% broken, n = 3). Units reported an increase in number of operation performed in 74% cases, improved surgery quality in 78%, and breadth of operations in 44%. Satisfaction, equipment suitability, reliability, and serviceability scored highly, with median values of 9 for all fields on a 10-point scale. CONCLUSIONS: Equipment donation positively impacts neurosurgical units in LMICs by allowing expansion of neurosurgical practice, improved safety and quality, and affordability. Adequate follow-up, considerations regarding equipment durability and maintenance needs, and improved support for repairs should be prioritized to ensure maximal benefit.

Molecular mechanisms for the activity of PX-478, an antitumor inhibitor of the hypoxia-inducible factor-1alpha.

We have reported previously that PX-478 (S-2-amino-3-[4'-N,N,-bis(chloroethyl)amino]phenyl propionic acid N-oxide dihydrochloride) has potent antitumor activity against a variety of human tumor xenografts associated with the levels of the hypoxia-inducible factor-1alpha (HIF-1alpha) within the tumor. We now report that PX-478 inhibits HIF-1alpha protein levels and transactivation in a variety of cancer cell lines. Hypoxia-induced vascular endothelial growth factor formation was inhibited by PX-478, whereas baseline levels of vascular endothelial growth factor in normoxia were unaffected. Studies of the mechanism of PX-478 action showed that HIF-1alpha inhibition occurs in both normoxia and hypoxia and does not require pVHL or p53. In addition, PX-478 decreases levels of HIF-1alpha mRNA and inhibits translation as determined by 35S labeling experiments and reporter assays using the 5' untranslated region of HIF-1alpha. Moreover, to a lesser extent, PX-478 also inhibits HIF-1alpha deubiquitination resulting in increased levels of polyubiquitinated HIF-1alpha. The inhibitory effect of PX-478 on HIF-1alpha levels is primarily due to its inhibition of translation because HIF-1alpha translation continues in hypoxia when translation of most proteins is decreased. We conclude that PX-478 inhibits HIF-1alpha at multiple levels that together or individually may contribute to its antitumor activity against HIF-1alpha-expressing tumors.

Identification of peptides from human pathogens able to cross-activate an HIV-1-gag-specific CD4+ T cell clone.

Antigen recognition by T cells is degenerate both at the MHC and the TCR level. In this study, we analyzed the cross-reactivity of a human HIV-1 gag p24-specific CD4(+) T cell clone obtained from an HIV-1-seronegative donor using a positional scanning synthetic combinatorial peptide library (PS-SCL)-based biometrical analysis. A number of decapeptides able to activate the HIV-1 gag-specific clone were identified and shown to correspond to sequences found in other human pathogens. Two of these peptides activated the T cell clone with the same stimulatory potency as the original HIV-1 gag p24 peptide. These findings show that an HIV-1-specific human T helper clone can react efficiently with peptides from other pathogens and suggest that cellular immune responses identified as being specific for one human pathogen (HIV-1) could arise from exposure to other pathogens.

Characterization of human immunodeficiency virus type 1 (HIV-1) Gag- and Gag peptide-specific CD4(+) T-cell clones from an HIV-1-seronegative donor following in vitro immunization.

Substantial evidence argues that human immunodeficiency virus type 1 (HIV-1)-specific CD4(+) T cells play an important role in the control of HIV-1 replication in infected individuals. Moreover, it is increasingly clear that an HIV vaccine should elicit potent cytotoxic lymphocyte and antibody responses that will likely require an efficient CD4(+) T-cell response. Therefore, understanding and characterizing HIV-specific CD4(+) T-cell responses is an important aim. Here we describe the generation of HIV-1 Gag- and Gag peptide-specific CD4(+) T-cell clones from an HIV-1-seronegative donor by in vitro immunization with HIV-1 Gag peptides. The Gag peptides were able to induce a strong CD4(+) T-cell immune response in peripheral blood mononuclear cells from the HIV-1-seronegative donor. Six Gag peptide-specific CD4(+) T-cell clones were isolated and their epitopes were mapped. The region of p24 between amino acids 201 and 300 of Gag was defined as the immunodominant region of Gag. A new T helper epitope in the p6 protein of Gag was identified. Two clones were shown to recognize Gag peptides and processed Gag protein, while the other four clones reacted only to Gag peptides under the experimental conditions used. Functional analysis of the clones indicated that both Th1 and Th2 types of CD4(+) T cells were obtained. One clone showed direct antigen-specific cytotoxic activity. These clones represent a valuable tool for understanding the cellular immune response to HIV-1, and the study provides new insights into the HIV-1-specific CD4(+) T-cell response and the induction of an anti-Gag and -Gag peptide cellular primary immune response in vitro.