Burnout in Surgical Residents of Underrepresented in Medicine Backgrounds: Key Influencing Factors and Possible Solutions.

INTRODUCTION: Alarming rates of burnout in surgical training pose a concern due to its deleterious effects on both patients and providers. Datum remains lacking on rates of burnout in surgical residents based on race and ethnicity. This study aims to document the frequency of burnout in surgical residents of racially underrepresented backgrounds and elucidate contributing factors. METHODS: A 35-question anonymized survey was distributed to general surgery residents from 23 programs between August 2018 and May 2019. This survey was designed from the validated Maslach Burnout Inventory, and included additional questions assessing participant demographics, educational, and social backgrounds. Responses were analyzed utilizing chi-square tests and Wilcoxon rank sum tests. There was also a free response portion of the survey which was evaluated using thematic analysis. RESULTS: We received 243 responses from 23 general surgery programs yielding a 9% (23/246) program response rate and 26% (243/935) response rate by surgical residents. One hundred and eighty-five participants (76%) identified as nonunderrepresented in medicine and 58 (24%) of participants identified as underrepresented in medicine. Fifty-three percent were male and 47% female. Overall, sixty-six percent of all surgical residents (n = 161) endorsed burnout with racially underrepresented residents reporting higher rates of burnout at 76% compared to 63% in their nonunderrepresented counterparts (P = 0.07). CONCLUSIONS: Although the generalizability of these results is limited, higher rates of reported burnout in racially underrepresented trainees noted in our study illuminates the need for continual dialogue on potential influencing factors and mitigation strategies.

Spatial and temporal analysis of road traffic crashes and ambulance responses in Lagos state, Nigeria.

BACKGROUND: Sub-Saharan African countries, Nigeria inclusive, are constrained by grossly limited access to quality pre-hospital trauma care services (PTCS). Findings from pragmatic approaches that explore spatial and temporal trends of past road crashes can inform novel interventions. To improve access to PTCS and reduce burden of road traffic injuries we explored geospatial trends of past emergency responses to road traffic crashes (RTCs) by Lagos State Ambulance Service (LASAMBUS), assessed efficiency of responses, and outcomes of interventions by local government areas (LGAs) of crash. METHODS: Using descriptive cross-sectional design and REDcap we explored pre-hospital care data of 1220 crash victims documented on LASAMBUS intervention forms from December 2017 to May 2018. We analyzed trends in days and times of calls, demographics of victims, locations of crashes and causes of delayed emergency responses. Assisted with STATA 16 and ArcGIS pro we conducted descriptive statistics and mapping of crash metrics including spatial and temporal relationships between times of the day, seasons of year, and crash LGA population density versus RTCs incidence. Descriptive analysis and mapping were used to assess relationships between 'Causes of Delayed response' and respective crash LGAs, and between Response Times and crash LGAs. RESULTS: Incidences of RTCs were highest across peak commuting hours (07:00-12:59 and 13:00-18:59), rainy season and harmattan (foggy) months, and densely populated LGAs. Five urban LGAs accounted for over half of RTCs distributions: Eti-Osa (14.7%), Ikeja (14.4%), Kosofe (9.9%), Ikorodu (9.7%), and Alimosho (6.6%). On intervention forms with a Cause of Delay, Traffic Congestion (60%), and Poor Description (17.8%), had associations with LGA distribution. Two densely populated urban LGAs, Agege and Apapa were significantly associated with Traffic Congestion as a Cause of Delay. LASAMBUS was able to address crash in only 502 (36.8%) of the 1220 interventions. Other notable outcomes include: No Crash (false calls) (26.6%), and Crash Already Addressed (22.17%). CONCLUSIONS: Geospatial analysis of past road crashes in Lagos state offered key insights into spatial and temporal trends of RTCs across LGAs, and identified operational constraints of state-organized PTCS and factors associated with delayed emergency responses. Findings can inform programmatic interventions to improve trauma care outcomes.

Phosphoprotein-based biomarkers as predictors for cancer therapy.

Disparities in cancer patient responses have prompted widespread searches to identify differences in sensitive vs. nonsensitive populations and form the basis of personalized medicine. This customized approach is dependent upon the development of pathway-specific therapeutics in conjunction with biomarkers that predict patient responses. Here, we show that Cdk5 drives growth in subgroups of patients with multiple types of neuroendocrine neoplasms. Phosphoproteomics and high throughput screening identified phosphorylation sites downstream of Cdk5. These phosphorylation events serve as biomarkers and effectively pinpoint Cdk5-driven tumors. Toward achieving targeted therapy, we demonstrate that mouse models of neuroendocrine cancer are responsive to selective Cdk5 inhibitors and biomimetic nanoparticles are effective vehicles for enhanced tumor targeting and reduction of drug toxicity. Finally, we show that biomarkers of Cdk5-dependent tumors effectively predict response to anti-Cdk5 therapy in patient-derived xenografts. Thus, a phosphoprotein-based diagnostic assay combined with Cdk5-targeted therapy is a rational treatment approach for neuroendocrine malignancies.

The American Association of Endocrine Surgeons Guidelines for the Definitive Surgical Management of Secondary and Tertiary Renal Hyperparathyroidism.

OBJECTIVE: To develop evidence-based recommendations for safe, effective, and appropriate treatment of secondary (SHPT) and tertiary (THPT) renal hyperparathyroidism. BACKGROUND: Hyperparathyroidism is common among patients with chronic kidney disease, end-stage kidney disease, and kidney transplant. The surgical management of SHPT and THPT is nuanced and requires a multidisciplinary approach. There are currently no clinical practice guidelines that address the surgical treatment of SHPT and THPT. METHODS: Medical literature was reviewed from January 1, 1985 to present January 1, 2021 by a panel of 10 experts in SHPT and THPT. Recommendations using the best available evidence was constructed. The American College of Physicians grading system was used to determine levels of evidence. Recommendations were discussed to consensus. The American Association of Endocrine Surgeons membership reviewed and commented on preliminary drafts of the content. RESULTS: These clinical guidelines present the epidemiology and pathophysiology of SHPT and THPT and provide recommendations for work-up and management of SHPT and THPT for all involved clinicians. It outlines the preoperative, intraoperative, and postoperative management of SHPT and THPT, as well as related definitions, operative techniques, morbidity, and outcomes. Specific topics include Pathogenesis and Epidemiology, Initial Evaluation, Imaging, Preoperative and Perioperative Care, Surgical Planning and Parathyroidectomy, Adjuncts and Approaches, Outcomes, and Reoperation. CONCLUSIONS: Evidence-based guidelines were created to assist clinicians in the optimal management of secondary and tertiary renal hyperparathyroidism.

Development of Human Adrenocortical Adenoma (HAA1) Cell Line from Zona Reticularis.

The human adrenal cortex is composed of distinct zones that are the main source of steroid hormone production. The mechanism of adrenocortical cell differentiation into several functionally organized populations with distinctive identities remains poorly understood. Human adrenal disease has been difficult to study, in part due to the absence of cultured cell lines that faithfully represent adrenal cell precursors in the early stages of transformation. Here, Human Adrenocortical Adenoma (HAA1) cell line derived from a patient's macronodular adrenocortical hyperplasia and was treated with histone deacetylase inhibitors (HDACis) and gene expression was examined. We describe a patient-derived HAA1 cell line derived from the zona reticularis, the innermost zone of the adrenal cortex. The HAA1 cell line is unique in its ability to exit a latent state and respond with steroidogenic gene expression upon treatment with histone deacetylase inhibitors. The gene expression pattern of differentiated HAA1 cells partially recreates the roster of genes in the adrenal layer that they have been derived from. Gene ontology analysis of whole genome RNA-seq corroborated increased expression of steroidogenic genes upon HDAC inhibition. Surprisingly, HDACi treatment induced broad activation of the Tumor Necrosis Factor (TNF) alpha pathway. This novel cell line we developed will hopefully be instrumental in understanding the molecular and biochemical mechanisms controlling adrenocortical differentiation and steroidogenesis.

Complications of traditional bonesetting in contemporary fracture care in low- and middle-income countries: A systematic review.

OBJECTIVE: To provide an overview of the evidence on the prevalence and pattern of complications among patients treated by traditional bonesetting presenting for modern orthopaedic services in low- and middle-income countries (LMIC). METHODS: Systematic review following PRISMA guidelines. Articles were identified by searching PubMed, Embase, ScienceDirect, SCOPUS, and Web of Science using the keywords "fracture care", "traditional bonesetters" and "complications". Papers included for review were original articles set in an LMIC that directly reported the prevalence and pattern of musculoskeletal complications of traditional bonesetters' fracture treatment in LMIC settings. RESULTS: A total of 176 papers were screened for eligibility and 15 studies were finally included. Nine were prospective studies, six were retrospective studies. All were hospital-based, observational studies that investigated the outcomes of treatment of fractures by traditional bonesetters published between 1986 and 2018. In total, this review covers 1389 participants with 1470 complications of fracture treatment. CONCLUSION: Traditional bonesetting complications are associated with significant morbidity. However, traditional bonesetters have the potential to contribute positively to primary fracture care when they are trained.

Academic Global Surgery Curricula: Current Status and a Call for a More Equitable Approach.

INTRODUCTION: We aimed to search the literature for global surgical curricula, assess if published resources align with existing competency frameworks in global health and surgical education, and determine if there is consensus around a fundamental set of competencies for the developing field of academic global surgery. METHODS: We reviewed SciVerse SCOPUS, PubMed, African Medicus Index, African Journals Online (AJOL), SciELO, Latin American and Caribbean Health Sciences Literature (LILACS) and Bioline for manuscripts on global surgery curricula and evaluated the results using existing competency frameworks in global health and surgical education from Consortium of the Universities for Global Health (CUGH) and Accreditation Council for Graduate Medical Education (ACGME) professional competencies. RESULTS: Our search generated 250 publications, of which 18 were eligible: (1) a total of 10 reported existing competency-based curricula that were concurrent with international experiences, (2) two reported existing pre-departure competency-based curricula, (3) six proposed theoretical competency-based curricula for future global surgery education. All, but one, were based in high-income countries (HICs) and focused on the needs of HIC trainees. None met all 17 competencies, none cited the CUGH competency on "Health Equity and Social Justice" and only one mentioned "Social and Environmental Determinants of Health." Only 22% (n = 4) were available as open-access. CONCLUSION: Currently, there is no universally accepted set of competencies on the fundamentals of academic global surgery. Existing literature are predominantly by and for HIC institutions and trainees. Current frameworks are inadequate for this emerging academic field. The field needs competencies with explicit input from LMIC experts to ensure creation of educational resources that are accessible and relevant to trainees from around the world.

Global community perception of 'surgical care' as a public health issue: a cross sectional survey.

BACKGROUND: In the last decade surgical care has been propelled into the public health domain with the establishment of a World Health Organisation (WHO) designated programme and key publications. The passing of the historic World Health Assembly Resolution (WHA) acknowledged surgical care as a vital component towards achieving Universal Health Coverage (UHC). We conducted the first worldwide survey to explore the perception of surgical care as a public health issue. METHOD: The anonymous, cross sectional survey targeted worldwide participants across a range of professional backgrounds, including non-medical using virtual snowball sampling method (in English) using Google Forms (Google Inc., Mountain View, CA, USA) from 20th February 2019 to 25th June 2019. The survey questions were designed to gauge awareness on Sustainable Development Goals (SDGs), UHC, WHO programmes and key publications on surgical care as well as perception of surgical care as a priority topic in public health. RESULTS: The survey was completed by 1954 respondents from 118 countries. Respondents were least aware of surgical care as a teaching topic in public health courses (27%; n = 526) and as a WHO programme (20%; n = 384). 82% of respondents were aware of UHC (n = 1599) and of this 72% (n = 1152) agreed that surgical care fits within UHC. While 77% (n = 1495) of respondents were aware of SDGs, only 19% (n = 370) agreed that surgery was a priority to meet SDGs. 48% (n = 941) rated surgical care as a cost-effective component of Primary Health Care. 88% (n = 1712) respondents had not read the WHA Resolution on 'Strengthening emergency and essential surgical care and anaesthesia as a component of UHC'. CONCLUSION: There is still a widespread gap in awareness on the importance of surgical care as a public health issue amongst our respondents. Surgical care was not seen as a priority to reach the SDGs, less visible as a WHO programme and not perceived as an important topic for public health courses.

A Call to Action: Black/African American Women Surgeon Scientists, Where are They?

OBJECTIVE: To determine the representation of Black/AA women surgeons in academic medicine among U.S. medical school faculty and to assess the number of NIH grants awarded to Black/AA women surgeon-scientists over the past 2 decades. SUMMARY OF BACKGROUND DATA: Despite increasing ethnic/racial and sex diversity in U.S. medical schools and residencies, Black/AA women have historically been underrepresented in academic surgery. METHODS: A retrospective review of the Association of American Medical Colleges 2017 Faculty Roster was performed and the number of grants awarded to surgeons from the NIH (1998-2017) was obtained. Data from the Association of American Medical Colleges included the total number of medical school surgery faculty, academic rank, tenure status, and department Chair roles. Descriptive statistics were performed. RESULTS: Of the 15,671 U.S. medical school surgical faculty, 123 (0.79%) were Black/AA women surgeons with only 11 (0.54%) being tenured faculty. When stratified by academic rank, 15 (12%) Black/AA women surgeons were instructors, 73 (59%) were assistant professors, 19 (15%) were associate professors, and 10 (8%) were full professors of surgery. Of the 372 U.S. department Chairs of surgery, none were Black/AA women. Of the 9139 NIH grants awarded to academic surgeons from 1998 and 2017, 31 (0.34%) grants were awarded to fewer than 12 Black/AA women surgeons. CONCLUSION: A significant disparity in the number of Black/AA women in academic surgery exists with few attaining promotion to the rank of professor with tenure and none ascending to the role of department Chair of surgery. Identifying and removing structural barriers to promotion, NIH grant funding, and academic advancement of Black/AA women as leaders and surgeon-scientists is needed.

Decreasing Trends in Road Traffic Injury Incidence and Mortality in Nigeria: A Ten-Year Analysis.

BACKGROUND: Road traffic accidents constitute a significant public health burden in Nigeria. In this study, we aim to (1) characterize the temporal burden of road traffic injury (RTI) and mortality rates in Nigeria over a decade, (2) identify regional RTI incidence, mortality trends, and high-risk regions, and (3) assess the impact of state population on injury and mortality. MATERIALS AND METHODS: We retrospectively reviewed aggregate state-level RTI incidence and mortality counts reported by the Federal Road Safety Corps from January 2001 through December 2010. We also reviewed population data from the National Population Commission. In addition to national analyses, regional analyses were performed in Nigeria's six geopolitical zones and one Federal Capital Territory (FCT). Regression analysis was also performed to determine the relationship between population and RTI incidence and mortality. RESULTS: The national median RTI incidence and mortality rates declined by 53% and 75%, respectively, between 2001 and 2010. Analysis by geopolitical zone yielded the greatest increases for both injury and mortality in the FCT and the greatest decreases for both in the South-South region. The average geopolitical zone, apart from the FCT, experienced a 24% decrease in the incidence rate and a 69% decrease in the mortality rate. An analysis of variance, run to assess potential differences in RTI incidence and mortality rates by state population, yielded significant values of P = 0.0023 for injury and P = 0.0002 for mortality. CONCLUSIONS: Acknowledging the potential for underreporting, a more holistic surveillance approach would generate more accurate data for future policy creation to improve clinical outcomes.

Rapid Relief: Thyroidectomy is a Quicker Cure than Radioactive Iodine Ablation (RAI) in Patients with Hyperthyroidism.

BACKGROUND: Time to hormonal control after definitive management of hyperthyroidism is unknown but may influence patient and physician decision making when choosing between treatment options. The hypothesis is that the euthyroid state is achieved faster after thyroidectomy than RAI ablation. METHODS: A retrospective review of all patients undergoing definitive therapy for hyperthyroidism was performed. Outcomes after thyroidectomy were compared to RAI. RESULTS: Over 3 years, 217 patients underwent definitive therapy for hyperthyroidism at a county hospital: 121 patients received RAI, and 96 patients underwent thyroidectomy. Age was equivalent (p = 0.72). More males underwent RAI (25% vs 15%, p = 0.05). Endocrinologists referred for both treatments equally (p = 0.82). Both treatments were offered after a minimum 1-year trial of medical management (p = 0.15). RAI patients mostly had Graves (93%), versus 73% of thyroidectomy patients (p < 0.001). Thyroidectomy patients more frequently had eye symptoms (35% vs 13%, p < 0.001), compressive symptoms (74% vs 15%, p < 0.001), or were pregnant/nursing (14% vs 0, p < 0.001). While the thyroidectomy patients had a documented discussion of all treatment modalities, 79% of RAI patients did not have a documented discussion regarding the option of surgical management (p < 0.001). Both treatment groups achieved an euthyroid state (71% vs 65%, p = 0.39). Thyroidectomy patients became euthyroid faster [3 months (2-7 months) versus 9 months (4-14 months); p < 0.001]. CONCLUSIONS: Thyroidectomy for hyperthyroidism renders a patient to an euthyroid state faster than RAI. This finding may be important for patients and clinicians considering definitive options for hyperthyroidism.

Contralateral adrenal abnormalities in Conn's syndrome.

BACKGROUND: During the course of evaluation for primary hyperaldosteronism, cross-sectional imaging is obtained in efforts to identify patients with an aldosterone producing adenoma (APA). A subset of these patients will have a synchronous, contralateral adrenal abnormality. Adrenal vein sampling (AVS) further guides clinical decision making by identifying unilateral (APA) versus bilateral hypersecretion. In the subset of patients with contralateral adrenal abnormalities, it is unclear how this affects the durability of an adrenalectomy for APA. This study characterizes this group of patients to assess the efficacy of surgical intervention. METHODS: A retrospective review of patients undergoing adrenalectomy for APA based on AVS at a university practice. Preoperative and postoperative patient characteristics, laboratory evaluations, imaging results, and final pathology were noted. RESULTS: From 2000 to 2011, 103 patients with APA underwent unilateral adrenalectomy. Eighteen patients (17%) had discordant results between AVS and imaging. Most of these patients were male (78%), and the mean age was 57 ± 13 y. Median duration of follow-up was 3.5 y [1 y, 6 y]. All patients with initial hypokalemia were rendered normokalemic after the operation. Four patients increased their antihypertensive regimen during the follow-up period. These patients all had nodular hyperplasia on final pathology. CONCLUSIONS: In patients with bilateral adrenal abnormalities who have undergone unilateral adrenalectomy for primary hyperaldosteronism, patients with clear APAs on final pathology appear to have durable outcomes after resection. Conversely, nodular hyperplasia on final pathology may be a risk factor for ongoing aldosterone hypersecretion. An algorithm for biochemical surveillance in this subset of patients should be considered.

Early endocrine attending surgeon presence increases operating room efficiency.

BACKGROUND: Preincision operating room (OR) preparation varies greatly. Cases requiring exacting preoperative setup may be more sensitive to inconsistent team members and trainees. Leadership and oversight by the surgeon may facilitate a timely start. The study hypothesized that early attending presence in the OR expedites surgery start time, improving efficiency, and decreasing cost. METHODS: Prospective data collection of endocrine surgery cases at an urban teaching hospital was performed. Time points recorded in minutes. Cost/min of OR time was $54. Patients classified as in the OR ≤10 min before attending arrival or >10 min before attending arrival. RESULTS: A total of 227 cases (166 thyroid, 54 parathyroid, 10 adrenal) were performed over 14 mo. Of the patients, 128 were in the OR ≤10 min before attending arrival, and 99 patients were >10 min (3 ± 3 min versus 35 ± 14 min, P < 0.01). The ≤10 min procedures started sooner after patient arrival in OR (40 ± 11 versus 63 ± 19, P < 0.01) which equated to $1202 of savings before incision. Although attending time in the OR before incision was equivalent between groups for adrenal and parathyroid, time to incision was shorter in the ≤10 min groups, saving $2416 ± 477 and $1458 ± 244, respectively (P < 0.01). Attending time in OR before thyroidectomy was 13 min longer in ≤10 min than >10 min (P < 0.01), but incisions were made 20 min sooner (P < 0.01) equating to $1076 ± 120 in savings. CONCLUSIONS: Early attending presence in the OR shortens time to incision. For parathyroid and adrenal cases, this does not require additional surgeon time. In ORs without consistent teams, early attending presence in the OR improves efficiency and yields significant cost savings.

AN AGGRESSIVE TEMPORAL BONE SDHC PARAGANGLIOMA ASSOCIATED WITH INCREASED HIF-2α SIGNALING.

OBJECTIVE: To describe a patient with a germline succinate dehydrogenase (SDHC) gene mutation presenting with primary hyperparathyroidism and a large catecholamine-producing temporal bone paraganglioma (PGL). METHODS: Evaluation of a SDHC mutation-positive PGL tumor biology using staining for tyrosine hydroxylase (TH), hypoxia-inducible factors 1α (HIF-1α) and 2α (HIF-2α). RESULTS: A 66-year-old man was noted to have a lytic skull base mass during work-up for his primary hyperparathyroidism. Biochemical evaluation with 24-hour urine catecholamines and metanephrines revealed marked elevation of norepinephrine and normetanephrine. Genetic testing revealed a germline SDHC mutation. A partial excision of skull base tumor was performed, which upon further examination revealed PGL. Immunohistochemistry of skull base PGL demonstrated heavy expression of TH and HIF-2α but reduced expression of HIF-1α. The remaining skull base PGL was treated with adjuvant radiation therapy. The patient's normetanephrine levels significantly decreased after surgery and radiation. CONCLUSION: Here, we report an unusual case of a patient presenting with a germline SDHC mutation-related functional PGL along with concomitant primary hyperparathyroidism. The present case illustrates that overexpression of HIF-2α but not of HIF-1α is linked to the pathogenesis of SDHC mutation-related PGL, and it may be responsible for the aggressive clinical behavior of a usually indolent course of SDHC-related PGLs.

Health Care Disparities in Endocrine Surgical Disorders.

While there has been great progress in the past few decades in the management of endocrine surgery disorders, with adoption of new technologies and approaches, standardization of practice patterns, and guideline recommendations, unequal implementation of these improvement has led to differences in access and outcomes. Health disparities are well documented in this population; however, literature lacks discussion of strategies to decrease disparities. In this article, the authors will describe the current status of health care-related disparities in endocrine surgical care, and discuss opportunities for future investigation and issue an urgent call to action items.

Cultural competency and ethical behavior for collaboration in limited-resource settings: Guidelines from the Society of University Surgeons Academic Global Surgery Committee and the Association for Academic Global Surgery.

BACKGROUND: There are an increasing number of global surgery activities worldwide. With such tremendous growth, there is a potential risk for untoward interactions between high-income country members and low-middle income country members, leading to programmatic failure, poor results, and/or low impact. METHODS: Key concepts for cultural competency and ethical behavior were generated by the Academic Global Surgery Committee of the Society for University Surgeons in collaboration with the Association for Academic Global Surgery. Both societies ensured active participation from high-income countries and low-middle income countries. RESULTS: The guidelines provide a framework for cultural competency and ethical behavior for high-income country members when collaborating with low-middle income country partners by offering recommendations for: (1) preparation for work with low-middle income countries; (2) process standardization; (3) working with the local community; (4) limits of practice; (5) patient autonomy and consent; (6) trainees; (7) potential pitfalls; and (8) gray areas. CONCLUSION: The article provides an actionable framework to address potential cultural competency and ethical behavior issues in high-income country - low-middle income country global surgery collaborations.

Using parallel geocoding to analyse the spatial characteristics of road traffic injury occurrences across Lagos, Nigeria.

While efforts to understand and mitigate road traffic injury (RTI) occurrence have long been underway in high-income countries, similar projects in low/middle-income countries (LMICs) are frequently hindered by institutional and informational obstacles. Technological advances in geospatial analysis provide a pathway to overcome a subset of these barriers, and in doing so enable researchers to create actionable insights in the pursuit of mitigating RTI-associated negative health outcomes. This analysis develops a parallel geocoding workflow to improve investigation of low-fidelity datasets common in LMICs. Subsequently, this workflow is applied to and evaluated on an RTI dataset from Lagos State, Nigeria, minimising positional error in geocoding by incorporating outputs from four commercially available geocoders. The concordance between outputs from these geocoders is evaluated, and spatial visualisations are generated to provide insight into the distribution of RTI occurrence within the analysis region. This study highlights the implications of geospatial data analysis in LMICs facilitated by modern technologies on health resource allocation, and ultimately, patient outcomes.

Identifying Hot Spots of Tuberculosis in Nigeria Using an Early Warning Outbreak Recognition System: Retrospective Analysis of Implications for Active Case Finding Interventions.

BACKGROUND: Undiagnosed tuberculosis (TB) cases are the major challenge to TB control in Nigeria. An early warning outbreak recognition system (EWORS) is a system that is primarily used to detect infectious disease outbreaks; this system can be used as a case-based geospatial tool for the real-time identification of hot spot areas with clusters of TB patients. TB screening targeted at such hot spots should yield more TB cases than screening targeted at non-hot spots. OBJECTIVE: We aimed to demonstrate the effectiveness of an EWORS for TB hot spot mapping as a tool for detecting areas with increased TB case yields in high TB-burden states of Nigeria. METHODS: KNCV Tuberculosis Foundation Nigeria deployed an EWORS to 14 high-burden states in Nigeria. The system used an advanced surveillance mechanism to identify TB patients' residences in clusters, enabling it to predict areas with elevated disease spread (ie, hot spots) at the ward level. TB screening outreach using the World Health Organization 4-symptom screening method was conducted in 121 hot spot wards and 213 non-hot spot wards selected from the same communities. Presumptive cases identified were evaluated for TB using the GeneXpert instrument or chest X-ray. Confirmed TB cases from both areas were linked to treatment. Data from the hot spot and non-hot spot wards were analyzed retrospectively for this study. RESULTS: During the 16-month intervention, a total of 1,962,042 persons (n=734,384, 37.4% male, n=1,227,658, 62.6% female) and 2,025,286 persons (n=701,103, 34.6% male, n=1,324,183, 65.4% female) participated in the community TB screening outreaches in the hot spot and non-hot spot areas, respectively. Presumptive cases among all patients screened were 268,264 (N=3,987,328, 6.7%) and confirmed TB cases were 22,618 (N=222,270, 10.1%). The number needed to screen to diagnose a TB case in the hot spot and non-hot spot areas was 146 and 193 per 10,000 people, respectively. CONCLUSIONS: Active TB case finding in EWORS-mapped hot spot areas yielded higher TB cases than the non-hot spot areas in the 14 high-burden states of Nigeria. With the application of EWORS, the precision of diagnosing TB among presumptive cases increased from 0.077 to 0.103, and the number of presumptive cases needed to diagnose a TB case decreased from 14.047 to 10.255 per 10,000 people.

Specific inhibition of mitochondrial oxidative stress suppresses inflammation and improves cardiac function in a rat pneumonia-related sepsis model.

Using a mitochondria-targeted vitamin E (Mito-Vit-E) in a rat pneumonia-related sepsis model, we examined the role of mitochondrial reactive oxygen species in sepsis-mediated myocardial inflammation and subsequent cardiac contractile dysfunction. Sepsis was produced in adult male Sprague-Dawley rats via intratracheal injection of S. pneumonia (4 × 10(6) colony formation units per rat). A single dose of Mito-Vit-E, vitamin E, or control vehicle, at 21.5 µmol/kg, was administered 30 min postinoculation. Blood was collected, and heart tissue was harvested at various time points. Mito-Vit-E in vivo distribution was confirmed by mass spectrometry. In cardiac mitochondria, Mito-Vit-E improved total antioxidant capacity and suppressed H(2)O(2) generation, whereas vitamin E offered little effect. In cytosol, both antioxidants decreased H(2)O(2) levels, but only vitamin E strengthened antioxidant capacity. Mito-Vit-E protected mitochondrial structure and function in the heart during sepsis, demonstrated by reduction in lipid and protein oxidation, preservation of mitochondrial membrane integrity, and recovery of respiratory function. While both Mito-Vit-E and vitamin E suppressed sepsis-induced peripheral and myocardial production of proinflammatory cytokines (tumor necrosis factor-α, interleukin-1ß, and interleukin-6), Mito-Vit-E exhibited significantly higher efficacy (P < 0.05). Stronger anti-inflammatory action of Mito-Vit-E was further shown by its near-complete inhibition of sepsis-induced myeloperoxidase accumulation in myocardium, suggesting its effect on neutrophil infiltration. Echocardiography analysis indicated that Mito-Vit-E ameliorated cardiac contractility of sepsis animals, shown by improved fractional shortening and ejection fraction. Together, our data suggest that targeted scavenging of mitochondrial reactive oxygen species protects mitochondrial function, attenuates tissue-level inflammation, and improves whole organ activities in the heart during sepsis.