Discovery of Novel TLR7 Agonists as Systemic Agent for Combination With aPD1 for Use in Immuno-oncology.

We have designed and developed novel and selective TLR7 agonists that exhibited potent receptor activity in a cell-based reporter assay. In vitro, these agonists significantly induced secretion of cytokines IL-6, IL-1ß, IL-10, TNFa, IFNa, and IP-10 in human and mouse whole blood. Pharmacokinetic and pharmacodynamic studies in mice showed a significant secretion of IFNα and TNFα cytokines. When combined with aPD1 in a CT-26 tumor model, the lead compound showed strong synergistic antitumor activity with complete tumor regression in 8/10 mice dosed using the intravenous route. Structure-activity relationship studies enabled by structure-based designs of TLR7 agonists are disclosed.

Global Neurosurgery at the 76th World Health Assembly (2023): First Neurosurgery-Driven Resolution Calls for Micronutrient Fortification to Prevent Spina Bifida.

Since 2018, a neurosurgery delegation has been actively engaged and consistently present at the World Health Assembly. Recognizing the growing impact of neurosurgical diseases, the neurosurgery delegation participated in the 76th World Health Assembly in May 2023, advocating for timely, safe, and affordable global neurosurgical care. The delegation focused on forging new collaborations, strengthening the World Health Organization-World Federation of Neurosurgical Societies official relations, and actively supporting resolutions that impact the neurosurgical patients. However, there is a long advocacy journey ahead to address unmet neurosurgical needs. Patient-centered advocacy is an inherent task of our profession and the essence of the Global Neurosurgery Bogota Declaration of 2016. The highlight of the 76th World Health Assembly was the adoption of the first neurosurgery-driven resolution calling for micronutrient fortification to prevent spina bifida and other micronutrient deficiencies. For the last 4 years, the Global Alliance for Prevention of Spina Bifida, a group spearheaded by neurosurgeons, advocated for spina bifida prevention. This Alliance collaborated with many stakeholders, notably, the Colombian government to promote the resolution: "Accelerating efforts for preventing micronutrient deficiencies and their consequences, including spina bifida and other neural tube defects, through safe and effective food fortification." This is a proud milestone for the neurosurgical profession. There are many strategies available for neurosurgeons, when working together with elected leaders, other stakeholders, and allied professionals, to implement initiatives that can prevent future cases of spina bifida and other neurological disorders and reduce the burden of neurosurgical disease.

Academic global surgical competencies: A modified Delphi consensus study.

Academic global surgery is a rapidly growing field that aims to improve access to safe surgical care worldwide. However, no universally accepted competencies exist to inform this developing field. A consensus-based approach, with input from a diverse group of experts, is needed to identify essential competencies that will lead to standardization in this field. A task force was set up using snowball sampling to recruit a broad group of content and context experts in global surgical and perioperative care. A draft set of competencies was revised through the modified Delphi process with two rounds of anonymous input. A threshold of 80% consensus was used to determine whether a competency or sub-competency learning objective was relevant to the skillset needed within academic global surgery and perioperative care. A diverse task force recruited experts from 22 countries to participate in both rounds of the Delphi process. Of the n = 59 respondents completing both rounds of iterative polling, 63% were from low- or middle-income countries. After two rounds of anonymous feedback, participants reached consensus on nine core competencies and 31 sub-competency objectives. The greatest consensus pertained to competency in ethics and professionalism in global surgery (100%) with emphasis on justice, equity, and decolonization across multiple competencies. This Delphi process, with input from experts worldwide, identified nine competencies which can be used to develop standardized academic global surgery and perioperative care curricula worldwide. Further work needs to be done to validate these competencies and establish assessments to ensure that they are taught effectively.

South Africa and the Surgical Diaspora-A Hub for Surgical Migration and Training.

BACKGROUND: The shortage of trained surgeons, anesthesiologists, and obstetricians is a major contributor to the unmet need for surgical care in low- and middle-income countries, and the shortage is aggravated by migration to higher-income countries. METHODS: We performed a cross-sectional observational study, combining individual-level data of 43,621 physicians from the Health Professions Council of South Africa with data from the registers of 14 high-income countries, and international statistics on surgical workforce, in order to quantify migration to and from South Africa in both absolute and relative terms. RESULTS: Of 6670 surgeons, anesthesiologists, and obstetricians in South Africa, a total of 713 (11%) were foreign medical graduates, and 396 (6%) were from a low- or middle-income country. South Africa was an important destination primarily for physicians originating from low-income countries; 2% of all surgeons, anesthesiologists, and obstetricians from low- and middle-income countries were registered in South Africa, and 6% in the other 14 recipient countries. A total of 1295 (16%) South African surgeons, anesthesiologists, and obstetricians worked in any of the 14 studied high-income countries. CONCLUSION: South Africa is an important regional hub for surgical migration and training. A notable proportion of surgical specialists in South Africa were medical graduates from other low- or middle-income countries, whereas migration out of South Africa to high-income countries was even larger.

Global Neurosurgery: Progress and Resolutions at the 75th World Health Assembly.

Neurosurgical advocates for global surgery/neurosurgery at the 75th World Health Assembly gathered in person for the first time after the COVID-19 pandemic in Geneva, Switzerland, in May 2022. This article reviews the significant progress in the global health landscape targeting neglected neurosurgical patients, emphasizing high-level policy advocacy and international efforts to support a new World Health Assembly resolution in mandatory folic acid fortification to prevent neural tube defects. The process of developing global resolutions through the World Health Organization and its member states is summarized. Two new global initiatives focused on the surgical patients among the most vulnerable member states are discussed, the Global Surgery Foundation and the Global Action Plan on Epilepsy and other Neurological Disorders. Progress toward a neurosurgery-inspired resolution on mandatory folic acid fortification to prevent spina bifida-folate is described. In addition, priorities for moving the global health agenda forward for the neurosurgical patient as it relates to the global burden of neurological disease are reviewed after the COVID-19 pandemic.

An Umbrella Review With Meta-Analysis of Chest Computed Tomography for Diagnosis of COVID-19: Considerations for Trauma Patient Management.

Background: RT-PCR testing is the standard for diagnosis of COVID-19, although it has its suboptimal sensitivity. Chest computed tomography (CT) has been proposed as an additional tool with diagnostic value, and several reports from primary and secondary studies that assessed its diagnostic accuracy are already available. To inform recommendations and practice regarding the use of chest CT in the in the trauma setting, we sought to identify, appraise, and summarize the available evidence on the diagnostic accuracy of chest CT for diagnosis of COVID-19, and its application in emergency trauma surgery patients; overcoming limitations of previous reports regarding chest CT accuracy and discussing important considerations regarding its role in this setting. Methods: We conducted an umbrella review using Living Overview of Evidence platform for COVID-19, which performs regular automated searches in MEDLINE, Embase, Cochrane Central Register of Controlled Trials, and more than 30 other sources. The review was conducted following the JBI methodology for systematic reviews. The Grading of Recommendations, Assessment, Development, and Evaluation approach for grading the certainty of the evidence is reported (registered in International Prospective Register of Systematic Reviews, CRD42020198267). Results: Thirty studies that fulfilled selection criteria were included; 19 primary studies provided estimates of sensitivity (0.91, 95%CI = [0.88-0.93]) and specificity (0.73, 95%CI = [0.61; 0.82]) of chest CT for COVID-19. No correlation was found between sensitivities and specificities (ρ = 0.22, IC95% [-0.33; 0.66]). Diagnostic odds ratio was estimated at: DOR = 27.5, 95%CI (14.7; 48.5). Evidence for sensitivity estimates was graded as MODERATE, and for specificity estimates it was graded as LOW. Conclusion: The value of chest CT appears to be that of an additional screening tool that can easily detect PCR false negatives, which are reportedly highly frequent. Upon the absence of PCR testing and impossibility to perform RT-PCR in trauma patients, chest CT can serve as a substitute with increased value and easy implementation. Systematic Review Registration: [www.crd.york.ac.uk/prospero], identifier [CRD42020198267].

Differential requirement for DICER1 activity during the development of mitral and tricuspid valves.

Mitral and tricuspid valves are essential for unidirectional blood flow in the heart. They are derived from similar cell sources, and yet congenital dysplasia affecting both valves is clinically rare, suggesting the presence of differential regulatory mechanisms underlying their development. Here, we specifically inactivated Dicer1 in the endocardium during cardiogenesis and found that Dicer1 deletion caused congenital mitral valve stenosis and regurgitation, whereas it had no impact on other valves. We showed that hyperplastic mitral valves were caused by abnormal condensation and extracellular matrix (ECM) remodeling. Our single-cell RNA sequencing analysis revealed impaired maturation of mesenchymal cells and abnormal expression of ECM genes in mutant mitral valves. Furthermore, expression of a set of miRNAs that target ECM genes was significantly lower in tricuspid valves compared to mitral valves, consistent with the idea that the miRNAs are differentially required for mitral and tricuspid valve development. We thus reveal miRNA-mediated gene regulation as a novel molecular mechanism that differentially regulates mitral and tricuspid valve development, thereby enhancing our understanding of the non-association of inborn mitral and tricuspid dysplasia observed clinically.

Preoperative Quadratus Lumborum Block Reduces Opioid Requirements in the Immediate Postoperative Period Following Hip Arthroscopy: A Randomized, Blinded Clinical Trial.

PURPOSE: To examine acute postoperative opioid consumption in patients undergoing hip arthroscopy and randomized to either receive a preoperative lateral quadratus lumborum block or sham injection. METHODS: This trial randomized 46 subjects undergoing hip arthroscopy with a single surgeon to receive a preoperative lateral quadratus lumborum block (40 mL, ropivacaine 0.25%) or sham injection. The primary outcome was postoperative opioid consumption in patients with and without a block. All opioid medications were converted to morphine milligram equivalents for comparisons. Categorical data were compared with χ2 tests and Fisher exact tests where appropriate. Continuous data were compared with 2-sided t-test and Wilcoxon rank-sum tests. RESULTS: Forty-six subjects scheduled for elective hip arthroscopy were successfully consented and randomized. Demographic and clinical characteristics did not differ. Postoperative opioid consumption decreased 28.3% in patients who received a preoperative lateral quadratus lumborum block (P = .04). Total perioperative opioid consumption (intraoperative and postoperative combined) was reduced 20% in the block group; however, this did not achieve statistical significance (P = .05). Three subjects in the sham group (12.5%) required unblinding for a rescue block in the postoperative anesthetic care unit (PACU) for uncontrolled pain despite systemic analgesics. While cold sensation was decreased postoperatively over the abdomen (P < .001) and anterior thigh (P = .03) in the block group, other PACU variables did not differ, including VAS pain scores, motor function, side effects, PACU duration, and patient satisfaction. CONCLUSIONS: Opioid consumption was reduced in patients who received a preoperative lateral quadratus lumborum block combined with a standardized, multimodal protocol as compared with patients who did not receive a block. Our findings support the growing evidence that quadratus lumborum blocks are an effective component of multimodal analgesia options for patients undergoing elective hip arthroscopy. LEVEL OF EVIDENCE: Level I, randomized controlled trial.

Global surgery, obstetric, and anaesthesia indicator definitions and reporting: An Utstein consensus report.

BACKGROUND: Indicators to evaluate progress towards timely access to safe surgical, anaesthesia, and obstetric (SAO) care were proposed in 2015 by the Lancet Commission on Global Surgery. These aimed to capture access to surgery, surgical workforce, surgical volume, perioperative mortality rate, and catastrophic and impoverishing financial consequences of surgery. Despite being rapidly taken up by practitioners, data points from which to derive the indicators were not defined, limiting comparability across time or settings. We convened global experts to evaluate and explicitly define-for the first time-the indicators to improve comparability and support achievement of 2030 goals to improve access to safe affordable surgical and anaesthesia care globally. METHODS AND FINDINGS: The Utstein process for developing and reporting guidelines through a consensus building process was followed. In-person discussions at a 2-day meeting were followed by an iterative process conducted by email and virtual group meetings until consensus was reached. The meeting was held between June 16 to 18, 2019; discussions continued until August 2020. Participants consisted of experts in surgery, anaesthesia, and obstetric care, data science, and health indicators from high-, middle-, and low-income countries. Considering each of the 6 indicators in turn, we refined overarching descriptions and agreed upon data points needed for construction of each indicator at current time (basic data points), and as each evolves over 2 to 5 (intermediate) and >5 year (full) time frames. We removed one of the original 6 indicators (one of 2 financial risk protection indicators was eliminated) and refined descriptions and defined data points required to construct the 5 remaining indicators: geospatial access, workforce, surgical volume, perioperative mortality, and catastrophic expenditure. A strength of the process was the number of people from global institutes and multilateral agencies involved in the collection and reporting of global health metrics; a limitation was the limited number of participants from low- or middle-income countries-who only made up 21% of the total attendees. CONCLUSIONS: To track global progress towards timely access to quality SAO care, these indicators-at the basic level-should be implemented universally as soon as possible. Intermediate and full indicator sets should be achieved by all countries over time. Meanwhile, these evolutions can assist in the short term in developing national surgical plans and collecting more detailed data for research studies.

Chest Computed Tomography for the Diagnosis of COVID-19 in Emergency Trauma Surgery Patients Who Require Urgent Care During the Pandemic: Protocol for an Umbrella Review.

BACKGROUND: Many health care facilities in low- and middle-income countries are inadequately resourced. COVID-19 has the potential to decimate surgical health care services unless health systems take stringent measures to protect health care workers from viral exposure and ensure the continuity of specialized care for patients. Among these measures, the timely diagnosis of COVID-19 is paramount to ensure the use of protective measures and isolation of patients to prevent transmission to health care personnel caring for patients with an unknown COVID-19 status or contact during the pandemic. Besides molecular and antibody tests, chest computed tomography (CT) has been assessed as a potential tool to aid in the screening or diagnosis of COVID-19 and could be valuable in the emergency care setting. OBJECTIVE: This paper presents the protocol for an umbrella review that aims to identify and summarize the available literature on the diagnostic accuracy of chest CT for COVID-19 in trauma surgery patients requiring urgent care. The objective is to inform future recommendations on emergency care for this category of patients. METHODS: We will conduct several searches in the L·OVE (Living Overview of Evidence) platform for COVID-19, a system that performs automated regular searches in PubMed, Embase, Cochrane Central Register of Controlled Trials, and over 30 other sources. The search results will be presented according to PRISMA (Preferred Reporting Items for Systematic Review and Meta-Analysis). This review will preferentially consider systematic reviews of diagnostic test accuracy studies, as well as individual studies of such design, if not included in the systematic reviews, that assessed the sensitivity and specificity of chest CT in emergency trauma surgery patients. Critical appraisal of the included studies for risk of bias will be conducted. Data will be extracted using a standardized data extraction tool. Findings will be summarized narratively, and the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach will be used to grade the certainty of evidence. RESULTS: Ethics approval is not required for this systematic review, as there will be no patient involvement. The search for this systematic review commenced in October 2020, and we expect to publish the findings in early 2021. The plan for dissemination is to publish the findings in a peer-reviewed journal and present our results at conferences that engage the most pertinent stakeholders. CONCLUSIONS: During the COVID-19 pandemic, protecting health care workers from infection is essential. Up-to-date information on the efficacy of diagnostic tests for detecting COVID-19 is essential. This review will serve an important role as a thorough summary to inform evidence-based recommendations on establishing effective policy and clinical guideline recommendations. TRIAL REGISTRATION: PROSPERO International Prospective Register of Systematic Reviews CRD42020198267; https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=198267. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/25207.

Discovery of Orally Active Isofuranones as Potent, Selective Inhibitors of Hematopoetic Progenitor Kinase 1.

While the discovery of immune checkpoint inhibitors has led to robust, durable responses in a range of cancers, many patients do not respond to currently available therapeutics. Therefore, an urgent need exists to identify alternative mechanisms to augment the immune-mediated clearance of tumors. Hematopoetic progenitor kinase 1 (HPK1) is a serine-threonine kinase that acts as a negative regulator of T-cell receptor (TCR) signaling, to dampen the immune response. Herein we describe the structure-based discovery of isofuranones as inhibitors of HPK1. Optimization of the chemotype led to improvements in potency, selectivity, plasma protein binding, and metabolic stability, culminating in the identification of compound 24. Oral administration of 24, in combination with an anti-PD1 antibody, demonstrated robust enhancement of anti-PD1 efficacy in a syngeneic tumor model of colorectal cancer.

Delivery of essential surgery by family physicians.

Primary health care provides the framework for delivering the socially-informed, comprehensive and patient-centred care underlying robust health-care systems and is, therefore, central to achieving universal health coverage. Family physicians are best placed to embody primary health care's dual focus on community and population health because they are often employed in rural or district hospitals with limited human resources, particularly a lack of specialists. Here we want to illustrate how additional training for family physicians, the key clinicians in primary care, can play a critical role in reducing disparities in access to surgical, obstetric and anaesthesia care in low- and middle-income countries and in rural or remote settings. Examples are given of how training programmes can be developed in low-resource settings to equip family physicians with life-saving surgical skills and of how family physicians in high-income countries can be trained in the surgical skills essential for working overseas in low-income settings. Policy-makers should promote surgical practice among family physicians by supporting family medicine programmes that include additional surgical skills training and by expanding opportunities and incentives for family physicians to serve in rural areas. Moreover, national surgical plans should include a primary health care strategy for surgical care and, globally, family physicians should be considered in discussions of surgical care. Finally, surgeons, anaesthesiologists, obstetricians and family physicians should be encouraged to collaborate in ensuring that all patients, regardless of place of residence, receive safe and timely surgical care.

Les soins de santé primaires établissent le cadre requis pour des soins complets adaptés aux patients, gages d'un système de santé solide. Ils jouent donc un rôle central dans la mise en place d'une couverture maladie universelle. Dans ce contexte, les médecins de famille sont les mieux placés pour incarner une double perspective, la santé communautaire et la santé des populations, car ils travaillent souvent dans des hôpitaux ruraux ou de district qui disposent de ressources humaines limitées, surtout en termes de spécialistes. Le présent document montre dans quelle mesure une formation complémentaire dédiée aux médecins de famille, acteurs clés des soins de santé primaires, peut avoir un impact décisif sur la diminution des inégalités d'accès aux interventions chirurgicales, obstétriques et anesthésiques dans les pays à faible et moyen revenu, ainsi que dans les milieux ruraux ou isolés. Il existe de nombreux exemples qui illustrent la façon dont les programmes de formation peuvent être mis en œuvre dans les endroits manquant de ressources afin que les médecins de famille acquièrent des compétences chirurgicales vitales, et qui indiquent comment les médecins de famille des pays à haut revenu peuvent apprendre des techniques de chirurgie essentielles pour travailler outre-mer ou dans des régions plus défavorisées. Les législateurs devraient promouvoir la pratique chirurgicale chez les médecins de famille en soutenant les programmes qui incluent une formation complémentaire aux techniques de chirurgie, et en multipliant les opportunités et sources de motivation pour que les médecins de famille exercent dans les zones rurales. Par ailleurs, les projets nationaux devraient comporter une stratégie de soins de santé primaires pour les actes chirurgicaux et, globalement, les médecins de famille devraient être pris en compte dans les discussions consacrées aux interventions chirurgicales. Enfin, chirurgiens, anesthésistes, obstétriciens et médecins de famille devraient être encouragés à collaborer pour s'assurer que tous les patients, quel que soit leur lieu de résidence, puissent bénéficier de soins chirurgicaux au moment opportun et en toute sécurité.

La atención primaria de salud establece el marco para la prestación de una atención socialmente informada, integral y centrada en el paciente, que es la base de los sistemas sólidos de atención sanitaria y, por lo tanto, es fundamental para lograr la cobertura sanitaria universal. Los médicos de familia son los que mejor pueden asumir el doble enfoque de la atención primaria en la salud de la comunidad y de la población porque trabajan con frecuencia en hospitales rurales o de distrito que tienen recursos humanos limitados, en especial por la falta de especialistas. En este documento, se pretende ilustrar cómo la capacitación adicional de los médicos de familia, quienes son los profesionales clínicos clave en la atención primaria, puede desempeñar una función esencial en la reducción de las desigualdades que existen para acceder a los procedimientos quirúrgicos, obstétricos y de anestesia en los países de ingresos bajos y medios y en los zonas rurales o remotas. También se dan ejemplos de cómo se pueden elaborar programas de capacitación en entornos de bajos recursos para preparar a los médicos de familia con técnicas quirúrgicas que salvan vidas y de cómo se puede capacitar a los médicos de familia de los países de altos ingresos sobre las técnicas quirúrgicas esenciales para que trabajen en el extranjero en entornos de bajos ingresos. Los responsables de formular políticas deben promover la práctica quirúrgica entre los médicos de familia mediante su apoyo a los programas de medicina familiar que incluyan una capacitación adicional sobre técnicas quirúrgicas, así como la ampliación de las oportunidades y de los incentivos para que los médicos de familia presten servicios en las zonas rurales. Además, los planes quirúrgicos nacionales deben incluir una estrategia de atención primaria de salud para la intervención quirúrgica y, a nivel mundial, los médicos de familia se deben tener en cuenta en los debates sobre la intervención quirúrgica. Por último, se debe alentar a los cirujanos, anestesiólogos, obstetras y médicos de familia a que colaboren para garantizar que todos los pacientes, sea cual sea su lugar de residencia, reciban servicios quirúrgicos seguros y oportunos.

Design, Synthesis, and Structure-Activity Relationships of Novel Tetrahydroisoquinolino Benzodiazepine Dimer Antitumor Agents and Their Application in Antibody-Drug Conjugates.

A series of tetrahydroisoquinoline-based benzodiazepine dimers were synthesized and tested for in vitro cytotoxicity against a panel of cancer cell lines. Structure-activity relationship investigation of various spacers guided by molecular modeling studies helped to identify compounds with picomolar activity. Payload 17 was conjugated to anti-mesothelin and anti-fucosylated monosialotetrahexosylganglioside (FucGM1) antibodies using lysosome-cleavable valine-citrulline dipeptide linkers via heterogeneous lysine conjugation and bacterial transglutaminase-mediated site-specific conjugation. In vitro, these antibody drug conjugates (ADCs) exhibited significant cytotoxic and target-mediated selectivity on human cancer cell lines. The pharmacokinetics and efficacy of these ADCs were further evaluated in gastric and lung cancer xenograft models in mice. Consistent pharmacokinetic profiles, high target specificity, and robust antitumor activity were observed in these models after a single dose of the ADC-46 (0.02 µmol/kg).

Identifying essential components of surgical care delivery through quality improvement: An updated surgical assessment tool.

BACKGROUND: Surgical care is a cost-effective intervention with major public health impact. Yet, five billion people do not have access to surgical and anesthesia care. This overwhelming unmet need has generated a rising interest in scale-up of these services globally. The purpose of this research was to aggregate available guidelines and create a synthesized tool that could provide valuable information at the local, national, and international health system levels. METHODS: A systematic review identified current documents cataloging elements for surgical care provision. Items with a reported frequency of >30% were included in the initial draft of the Surgical Assessment Tool. This underwent two cycles of Delphi-method expert opinion elicitation from providers working in low- and middle-income settings. Finally, the tool underwent vetting by the World Health Organization to create an expert-endorsed survey. RESULTS: Fifteen surgical tools were identified, containing a total of 216 unique elements in the following domains: infrastructure (n = 152), service delivery (n = 49), and workforce (n = 15). The final tool consisted of 169 items in the following domains: infrastructure (n = 35), service delivery (n = 92), workforce (n = 20), information management (n = 10), and financing (n = 12). CONCLUSION: Informed planning is critical to ensure successful expansion of surgical services. Our analysis of current tools shows varying agreement on the essential components of surgical care delivery. This updated tool serves as a crucial method to systematically assess surgical systems as well as monitor, modify, and strengthen in a scalable fashion. Importantly, it has the potential to be used in all settings after adaptation to local context.

Measuring the migration of surgical specialists.

BACKGROUND: The lack of access to essential surgical care in low-income countries is aggravated by emigration of locally-trained surgical specialists to more affluent regions. Yet, the global diaspora of surgeons, obstetricians, and anesthesiologists from low-income and middle-income countries has never been fully described and compared with those who have remained in their country of origin. It is also unclear whether the surgical workforce is more affected by international migration than other medical specialists. In this study, we aimed to quantify the proportion of surgical specialists originating from low-income and middle-income countries that currently work in high-income countries. METHODS: We retrieved surgical workforce data from 48 high-income countries and 102 low-income and middle-income countries using the database of the World Health Organization Global Surgical Workforce. We then compared this domestic workforce with more granular data on the country of initial medical qualification of all surgeons, anesthesiologists, and obstetricians made available for 14 selected high-income countries to calculate the proportion of surgical specialists working abroad. RESULTS: We identified 1,118,804 specialist surgeons, anesthesiologists, or obstetricians from 102 low-income and middle-income countries, of whom 33,021 (3.0%) worked in the 14 included high-income countries. The proportion of surgical specialists abroad was greatest for the African and South East Asian regions (12.8% and 12.1%). The proportion of specialists abroad was not greater for surgeons, anesthesiologists, or obstetricians than for physicians and other medical specialists (P = .465). Overall, the countries with the lowest remaining density of surgical specialists were also the countries from which the largest proportion of graduates were now working in high-income countries (P = .011). CONCLUSION: A substantial proportion of all surgeons, anesthesiologists, and obstetricians from low-income and middle-income countries currently work in high-income countries. In addition to decreasing migration from areas of surgical need, innovative strategies to retain and strengthen the surgical workforce could involve engaging this large international pool of surgical specialists and instructors.

Management of infective complications of otitis media in resource-constrained settings.

PURPOSE OF REVIEW: Complications of otitis media are a cause of significant morbidity and mortality, compounded in resource-constrained settings in which human and physical resources to manage disease are suboptimal. Here, we examine the current best evidence to devise a protocol for management, in particular exploring the opportunity for conservative or nonspecialist management. RECENT FINDINGS: Reviews of the literature suggest that intratemporal and extracranial infections can be managed with antibiotics in the first instance, with aspiration or incision and drainage of abscess. Failure to respond necessitates mastoidectomy, which need not be extensive, and can be performed with hammer and gouge. Suspected or possible intracranial extension requires referral for computed tomography (CT) imaging. Intracranial infection can in some instances be managed with antibiotics, but large or persistent intracranial abscess, or the presence of cholesteatoma requires management in a centre for specialist surgery. SUMMARY: Many complications of otitis media could be managed by nonspecialists in appropriately equipped local or regional health facilities, and supported by appropriate training. However, regional centres with CT imaging and specialist surgery are required for assessment and treatment of cases that are suspected of having complex or advanced disease, or that fail to respond to initial treatment. Those involved in planning healthcare provision should look to develop infrastructure to support such management.

Neurosurgical Randomized Trials in Low- and Middle-Income Countries.

BACKGROUND: The setting of a randomized trial can determine whether its findings are generalizable and can therefore apply to different settings. The contribution of low- and middle-income countries (LMICs) to neurosurgical randomized trials has not been systematically described before. OBJECTIVE: To perform a systematic analysis of design characteristics and methodology, funding source, and interventions studied between trials led by and/or conducted in high-income countries (HICs) vs LMICs. METHODS: From January 2003 to July 2016, English-language trials with >5 patients assessing any one neurosurgical procedure against another procedure, nonsurgical treatment, or no treatment were retrieved from MEDLINE, Scopus, and Cochrane Library. Income classification for each country was assessed using the World Bank Atlas method. RESULTS: A total of 73.3% of the 397 studies that met inclusion criteria were led by HICs, whereas 26.7% were led by LMICs. Of the 106 LMIC-led studies, 71 were led by China. If China is excluded, only 8.8% were led by LMICs. HIC-led trials enrolled a median of 92 patients vs a median of 65 patients in LMIC-led trials. HIC-led trials enrolled from 7.6 sites vs 1.8 sites in LMIC-led studies. Over half of LMIC-led trials were institutionally funded (54.7%). The majority of both HIC- and LMIC-led trials evaluated spinal neurosurgery, 68% and 71.7%, respectively. CONCLUSION: We have established that there is a substantial disparity between HICs and LMICs in the number of published neurosurgical trials. A concerted effort to invest in research capacity building in LMICs is an essential step towards ensuring context- and resource-specific high-quality evidence is generated.

Global neurosurgery: continued momentum at the 72nd World Health Assembly.

Global neurosurgery is the practice of neurosurgery with the primary purpose of delivering timely, safe, and affordable neurosurgical care to all who need it. This field is led by neurosurgeons, and global neurosurgery sessions are now part of every major international neurosurgical meeting. The World Federation of Neurosurgical Societies (WFNS) is working to coordinate activities and align all related activities for greater impact. This report updates the contributions made by the WFNS-WHO Liaison Committee at the most recent World Health Assembly (WHA) in 2019. The WHA is a decision-making body of the World Health Organization (WHO), attended by its 194 Member States. The WFNS has maintained official relations as a nongovernmental organization with the WHO for over 30 years, and this year 15 neurosurgical delegates attended events during the WHA. Participation by neurosurgeons continues to grow as many WHA events focused on global surgery have intrinsically involved neurosurgical leadership and participation. This year, resolution WHA72.31, entitled "Emergency and trauma care, Emergency care systems for universal health coverage: ensuring timely care for the acutely ill and injured," was passed. This resolution provides further opportunities for neurosurgical advocacy as the landscape of global surgery gains recognition and momentum.

Management of paediatric burns in low- and middle-income countries: assessing capacity using the World Health Organization Surgical Assessment Tool.

BACKGROUND: Burns are a leading cause of global disease burden, with children in low- and middle-income countries (LMICs) disproportionately affected. Effective management improves outcomes; however, the availability of necessary resources in LMICs remains unclear. We evaluated surgical centres in LMICs using the WHO Surgical Assessment Tool (SAT) to identify opportunities to optimize paediatric burn care. METHODS: We reviewed WHO SAT database entries for 2010-2015. A total of 1121 facilities from 57 countries met the inclusion criteria: facilities with surgical capacity in LMICs operating on children. Human resources, equipment and infrastructure relevant to paediatric burn care were analysed by WHO Regional and World Bank Income Classifications and facility type. RESULTS: Facilities had an average of 147 beds and performed 485 paediatric operations annually. Discrepancies existed between procedures performed and resource availability; 86% of facilities performed acute burn care, but only 37% could consistently provide intravenous fluids. Many, particularly tertiary, centres performed contracture release and skin grafting (41%) and amputation (50%). CONCLUSIONS: LMICs have limited resources to provide paediatric burn care but widely perform many interventions necessary to address the burden of burns. The SAT may not capture innovative and traditional approaches to burn care. There remains an opportunity to improve paediatric burn care globally.