Does pre-injury clopidogrel use increase the risk of intracranial haemorrhage post head injury in adult patients? A systematic review and meta-analysis.

BACKGROUND: Several current guidelines do not include antiplatelet use as an explicit indication for CT scan of the head following head injury. The impact of individual antiplatelet agent use on rates of intracranial haemorrhage is unclear. The primary objective of this systematic review was to assess if clopidogrel monotherapy was associated with traumatic intracranial haemorrhage (tICH) on CT of the head within 24 hours of presentation following head trauma compared with no antithrombotic controls. METHODS: Eligible studies were non-randomised studies with participants aged ≥18 years old with head injury. Studies had to have conducted CT of the head within 24 hours of presentation and contain a no antithrombotic control group and a clopidogrel monotherapy group.Eight databases were searched from inception to December 2020. Assessment of identified studies against inclusion criteria and data extraction were carried out independently and in duplicate by two authors.Quality assessment and risk of bias (ROB) were assessed using the Newcastle-Ottawa Quality Assessment tool and Risk Of Bias In Non-randomised Studies of Interventions (ROBINS-I) tool. Meta-analysis was conducted using a random-effects model and reported as an OR and 95% CI. RESULTS: Seven studies were eligible for inclusion with a total of 21 898 participants that were incorporated into the meta-analysis. Five studies were retrospective. Clopidogrel monotherapy was not significantly associated with an increase in risk of tICH compared with no antithrombotic controls (OR 0.97, 95% CI 0.54 to 1.75). Heterogeneity was high with an I2 of 75%. Sensitivity analysis produced an I2 of 21% and did not show a significant association between clopidogrel monotherapy and risk of tICH (OR 1.16, 95% CI 0.87 to 1.55). All studies scored for moderate to serious ROB on categories in the ROBINS-I tool. CONCLUSION: Included studies were vulnerable to confounding and several were small-scale studies. The results should be interpreted with caution given the ROB identified. This study does not provide statistically significant evidence that clopidogrel monotherapy patients are at increased risk of tICH after head injury compared with no antithrombotic controls. PROSPERO REGISTRATION NUMBER: CRD42020223541.

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.

Differences in outcomes of mandatory motorcycle helmet legislation by country income level: A systematic review and meta-analysis.

BACKGROUND: The recent Lancet Commission on Legal Determinants of Global Health argues that governance can provide the framework for achieving sustainable development goals. Even though over 90% of fatal road traffic injuries occur in low- and middle-income countries (LMICs) primarily affecting motorcyclists, the utility of helmet laws outside of high-income settings has not been well characterized. We sought to evaluate the differences in outcomes of mandatory motorcycle helmet legislation and determine whether these varied across country income levels. METHODS AND FINDINGS: A systematic review and meta-analysis were completed using the PRISMA checklist. A search for relevant articles was conducted using the PubMed, Embase, and Web of Science databases from January 1, 1990 to August 8, 2021. Studies were included if they evaluated helmet usage, mortality from motorcycle crash, or traumatic brain injury (TBI) incidence, with and without enactment of a mandatory helmet law as the intervention. The Newcastle-Ottawa Scale (NOS) was used to rate study quality and funnel plots, and Begg's and Egger's tests were used to assess for small study bias. Pooled odds ratios (ORs) and their 95% confidence intervals (CIs) were stratified by high-income countries (HICs) versus LMICs using the random-effects model. Twenty-five articles were included in the final analysis encompassing a total study population of 31,949,418 people. There were 17 retrospective cohort studies, 2 prospective cohort studies, 1 case-control study, and 5 pre-post design studies. There were 16 studies from HICs and 9 from LMICs. The median NOS score was 6 with a range of 4 to 9. All studies demonstrated higher odds of helmet usage after implementation of helmet law; however, the results were statistically significantly greater in HICs (OR: 53.5; 95% CI: 28.4; 100.7) than in LMICs (OR: 4.82; 95% CI: 3.58; 6.49), p-value comparing both strata < 0.0001. There were significantly lower odds of motorcycle fatalities after enactment of helmet legislation (OR: 0.71; 95% CI: 0.61; 0.83) with no significant difference by income classification, p-value: 0.27. Odds of TBI were statistically significantly lower in HICs (OR: 0.61, 95% CI 0.54 to 0.69) than in LMICs (0.79, 95% CI 0.72 to 0.86) after enactment of law (p-value: 0.0001). Limitations of this study include variability in the methodologies and data sources in the studies included in the meta-analysis as well as the lack of available literature from the lowest income countries or from the African WHO region, in which helmet laws are least commonly present. CONCLUSIONS: In this study, we observed that mandatory helmet laws had substantial public health benefits in all income contexts, but some outcomes were diminished in LMIC settings where additional measures such as public education and law enforcement might play critical roles.

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.

Collaboration and topic switches in science.

Collaboration is a key driver of science and innovation. Mainly motivated by the need to leverage different capacities and expertise to solve a scientific problem, collaboration is also an excellent source of information about the future behavior of scholars. In particular, it allows us to infer the likelihood that scientists choose future research directions via the intertwined mechanisms of selection and social influence. Here we thoroughly investigate the interplay between collaboration and topic switches. We find that the probability for a scholar to start working on a new topic increases with the number of previous collaborators, with a pattern showing that the effects of individual collaborators are not independent. The higher the productivity and the impact of authors, the more likely their coworkers will start working on new topics. The average number of coauthors per paper is also inversely related to the topic switch probability, suggesting a dilution of this effect as the number of collaborators increases.

Is Pre-Injury Socioeconomic Status Associated With Outcomes in Patients With Traumatic Brain Injury? A Systematic Review.

While socioeconomic status (SES) is associated with a variety of health outcomes, the literature on the association between SES and traumatic brain injury (TBI) outcomes has not been formally summarized. This study aims to review existing literature to ascertain whether patients with low SES pre-injury have worse clinical outcomes after TBI compared with those with high SES, in high-income countries. A systematic search was conducted using the MEDLINE, Embase, and PsychINFO databases. Observational studies addressing the association between SES and TBI outcomes (mortality, functional, cognitive, and vocational outcomes) were included (published from 2000, written in English). Both pediatric and adult TBI groups were included. Thirty-two studies met the inclusion criteria. Measures of SES varied across studies. Mortality was assessed in seven studies; five reported an association between low SES and higher mortality. Five of eight studies showed an association between low SES and worse functional outcomes; results for cognitive (n = 13) and vocational outcomes (n = 10) were mixed. The results of this review suggest that SES is a variable of interest in the context of TBI outcomes and should be assessed at time of admission to assist in social work discharge planning and early mobilization of available community resources. Further work is required to better understand the impact of SES on TBI outcomes.

Consensus-Based Development of a Global Registry for Traumatic Brain Injury: Establishment, Protocol, and Implementation.

BACKGROUND AND OBJECTIVES: Global disparity exists in the demographics, pathology, management, and outcomes of surgically treated traumatic brain injury (TBI). However, the factors underlying these differences, including intervention effectiveness, remain unclear. Establishing a more accurate global picture of the burden of TBI represents a challenging task requiring systematic and ongoing data collection of patients with TBI across all management modalities. The objective of this study was to establish a global registry that would enable local service benchmarking against a global standard, identification of unmet need in TBI management, and its evidence-based prioritization in policymaking. METHODS: The registry was developed in an iterative consensus-based manner by a panel of neurotrauma professionals. Proposed registry objectives, structure, and data points were established in 2 international multidisciplinary neurotrauma meetings, after which a survey consisting of the same data points was circulated within the global neurotrauma community. The survey results were disseminated in a final meeting to reach a consensus on the most pertinent registry variables. RESULTS: A total of 156 professionals from 53 countries, including both high-income countries and low- and middle-income countries, responded to the survey. The final consensus-based registry includes patients with TBI who required neurosurgical admission, a neurosurgical procedure, or a critical care admission. The data set comprised clinically pertinent information on demographics, injury characteristics, imaging, treatments, and short-term outcomes. Based on the consensus, the Global Epidemiology and Outcomes following Traumatic Brain Injury (GEO-TBI) registry was established. CONCLUSION: The GEO-TBI registry will enable high-quality data collection, clinical auditing, and research activity, and it is supported by the World Federation of Neurosurgical Societies and the National Institute of Health Research Global Health Program. The GEO-TBI registry ( https://geotbi.org ) is now open for participant site recruitment. Any center involved in TBI management is welcome to join the collaboration to access the registry.

Microdialysis-Based Classifications of Abnormal Metabolic States after Traumatic Brain Injury: A Systematic Review of the Literature.

After traumatic brain injury (TBI), cerebral metabolism can become deranged, contributing to secondary injury. Cerebral microdialysis (CMD) allows cerebral metabolism assessment and is often used with other neuro-monitoring modalities. CMD-derived parameters such as the lactate/pyruvate ratio (LPR) show a failure of oxidative energy generation. CMD-based abnormal metabolic states can be described following TBI, informing the etiology of physiological derangements. This systematic review summarizes the published literature on microdialysis-based abnormal metabolic classifications following TBI. Original research studies in which the populations were patients with TBI were included. Studies that described CMD-based classifications of metabolic abnormalities were included in the synthesis of the narrative results. A total of 825 studies underwent two-step screening after duplicates were removed. Fifty-three articles that used CMD in TBI patients were included. Of these, 14 described abnormal metabolic states based on CMD parameters. Classifications were heterogeneous between studies. LPR was the most frequently used parameter in the classifications; high LPR values were described as metabolic crisis. Ischemia was consistently defined as high LPR with low CMD substrate levels (glucose or pyruvate). Mitochondrial dysfunction, describing inability to use energy substrate despite availability, was identified based on raised LPR with near-normal levels of pyruvate. This is the first systematic review summarizing the published literature on microdialysis-based abnormal metabolic states following TBI. Although variability exists among individual classifications, there is broad agreement about broad definitions of metabolic crisis, ischemia, and mitochondrial dysfunction. Identifying the etiology of deranged cerebral metabolism after TBI is important for targeting therapeutic interventions.

Women in leadership positions in European neurosurgery - Have we broken the glass ceiling?

Introduction: The proportion of male neurosurgeons has historically been higher than of women, although at least equal numbers of women have been entering European medical schools. The Diversity Committee (DC) of the European Association of Neurosurgical Societies (EANS) was founded recently to address this phenomenon. Research question: In this cross-sectional study, we aimed to characterize the status quo of female leadership by assessing the proportion of women heading European neurosurgical departments. Material and methods: European neurosurgical departments were retrieved from the EANS repository. The gender of all department chairs was determined via departmental websites or by personal contact. The proportion of females was stratified by region and by type of hospital (university versus non-university). Results: A total of 41 (4.3%) female department chairs were identified in 961 neurosurgery departments in 41 European countries. Two thirds (68.3%) of European countries do not have a female neurosurgery chair. The highest proportion of female chairs was found in Northern Europe (11.1%), owing to four female chairs in a relatively small number of departments (n = 36). The proportions were considerably smaller in Western Europe (n = 17/312 (5.5%)), Southern Europe (n = 14/353 (4.0%)) and Central and Eastern Europe (n = 6/260 (2.3%)) (p = 0.06). The distribution of female chairs in university (n = 19 (46.3%)) versus non-university departments (n = 22 (53.7%)) was even. Discussion and Conclusion: There is a significant gender imbalance with 4% of all European neurosurgery departments headed by women. The DC intends to develop strategies to support equal chances and normalize the presence of female leaders in European neurosurgery.

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.

Development, implementation and validation of resource-stratified guidelines in low-income and middle-income countries: a scoping review protocol.

INTRODUCTION: Nearly every field of medicine has some form of clinical practice guidelines. However, only within the past 5-10 years has the medical community acknowledged the need for well-developed guidelines tailored to the local healthcare needs and the resources available. In most low-income and middle-income countries (LMICs), healthcare workers depend on guidelines developed in high-income countries (HICs), yet many interventions validated in a HIC are ineffective when implemented in an LMIC. The variation in infrastructure, medical personnel, technology and environmental conditions exhibited in LMICs relative to HICs necessitates a careful appraisal of the evidence base used in clinical guideline recommendations. This review aims to map the use of resource-stratified guidelines across all fields of medicine. The review seeks to answer three questions for the identified guidelines: (1) what was the method of development, (2) have they been implemented and, if so, (3) have they been validated. METHODS: The search strategy will aim to locate studies from inception to November 2021. An initial limited search of PubMed and Scopus was undertaken to identify articles on the topic. The text words contained in the titles and abstracts of relevant articles, and the index terms used to describe the articles were used to develop a full search strategy for PubMed and Scopus. This scoping review will be conducted in accordance with the Joanna Briggs Institute (JBI) methodology for scoping reviews. Data to be extracted from each study will include population characteristics of both developers and intended implementation population, medical specialty, validation status, method of guideline development, whether the study is consensus or evidence-based in addition to a summary of recommendations for practice. ETHICS AND DISSEMINATION: Ethical approval is not required for this review. The plan for dissemination is to publish review findings in a peer-reviewed journal.

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.

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.

Unusual Presentation of a Swelling in the Achilles Tendon After an Acute Rupture: A Case Report.

INTRODUCTION: Achilles tendon rupture is common and most cases heal with appropriate treatment. However, complications in the treatment of this condition can be debilitating, especially for young, active individuals. CASE REPORT: We present the case of a 37-year-old man who presented with ongoing pain on weight-bearing and swelling in the left Achilles tendon area8 months after acute rupture treated with functional bracing and early rehabilitation. Magnetic resonance imaging showed intrasubstance thickening of the tendon with a large swelling. Successful decompression of the swelling was achieved using an arthroscopic technique and the patient returned to normal activities. CONCLUSION: Physiotherapy and return to normal activities were limited in our patient due to high levels of discomfort and pain. Prolonged immobility following tendon rupture has been shown to cause increased scar tissue proliferation. This may have hindered functional rehabilitation progress and negatively impacted on the reparative process.

Acute ischemic stroke diagnosis using brain tissue pulsations.

Healthy brain tissue pulsates with the cardiac cycle, but whether brain tissue pulsations (BTPs) are impaired by tissue ischemia due to ischemic stroke is currently unclear. This study is the first to explore the clinical potential of measuring BTPs using ultrasound in acute ischemic stroke patients. BTPs were measured in 24 healthy volunteers (aged 52-82 years) and 14 acute ischemic stroke patients (aged 51-86 years) using a novel Transcranial Tissue Doppler (TCTD) method. Measurements were quick to perform and were well tolerated by all subjects. A mixed-methods approach was used for blinded analysis of recordings. This identified qualitative disruption of BTPs in acute stroke patients, which were used to create an analysis checklist. Blinded BTP analysis by novices using the checklist resulted in high sensitivity but low specificity for stroke detection. Quantitative analysis also identified differences between stroke and healthy participants, including weaker BTPs in stroke patients. This first study reporting BTP characteristics in acute ischemic stroke revealed weaker brain tissue pulsations and waveform disruption in acute stroke patients. However, further clinical evaluation using a larger sample size is required to confirm these findings and to explore whether TCTD monitoring might be beneficial for clinical neuromonitoring.

Brain Tissue Pulsation in Healthy Volunteers.

It is well known that the brain pulses with each cardiac cycle, but interest in measuring cardiac-induced brain tissue pulsations (BTPs) is relatively recent. This study was aimed at generating BTP reference data from healthy patients for future clinical comparisons and modelling. BTPs were measured through the forehead and temporal positions as a function of age, sex, heart rate, mean arterial pressure and pulse pressure. A multivariate regression model was developed based on transcranial tissue Doppler BTP measurements from 107 healthy adults (56 male) aged from 20-81 y. A subset of 5 participants (aged 20-49 y) underwent a brain magnetic resonance imaging scan to relate the position of the ultrasound beam to anatomy. BTP amplitudes were found to vary widely between patients (from ∼4 to ∼150 µm) and were strongly associated with pulse pressure. Comparison with magnetic resonance images confirmed regional variations in BTP with depth and probe position.

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.

The National Motorcycle Helmet Law at 2 Years: Review of Its Impact on the Epidemiology of Traumatic Brain Injury in a Major Government Hospital in Cambodia.

BACKGROUND: Traumatic brain injury (TBI) is major contributor to the global burden of disease, especially in low- and middle- income countries, where most TBIs are traffic-related. Evidence shows that helmets protect against severe TBI. Cambodia continues to have the greatest motorcycle fatality rate in Southeast Asia. We investigated whether the National Motorcycle Helmet Law introduced in January 2016 had an impact on the epidemiology of motorcycle-related TBI in a neurosurgical referral center in Phnom Penh. METHODS: This is a cross-sectional study of all patients admitted to the Department of Neurosurgery at Preah Kossamak Hospital with TBI following motorcycle accidents between January 2014 and December 2017. RESULTS: TBI admissions increased (from 234 in 2014 to 768 in 2017). The median age was 26 years, and most patients were male. The percentage of helmeted patients was 9% in 2014 and 13% in 2015; this increased to 18% in 2016, but dropped to 9% in 2017. Most TBIs occurred during the evening rush hour. Since 2016, more patients wore helmets in the daytime (up to 23%) than at night (5% between 1:00 and 5:00 am). Skull fracture, the most common pathology pre-law, decreased by 25% post-law (P < 0.001). CONCLUSIONS: With growing urbanization and motorization, TBI is a significant cause of morbidity and mortality in Cambodia. Two years after helmets became compulsory, most patients with TBI are still unhelmeted. Likely contributing factors are low penalty for noncompliance and inconsistent law enforcement. TBI is a major public health problem warranting further efforts to understand how to improve prevention strategies and advocate for change.

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.