Poor oral health and the risk of esophageal squamous cell carcinoma in Malawi.

Esophageal squamous cell carcinoma (ESCC) is the second most common cancer in Malawi. Risk factors for this cancer in Malawi are poorly understood. Poor oral health has previously been linked to increased ESCC risk in other high-incidence regions, including parts of Eastern and Southern Africa. We assessed the relationship between oral health and ESCC risk in a sex, age and location frequency-matched case-control study based at two hospitals in Lilongwe, Malawi from 2017 to 2020. Trained interviewers used a structured questionnaire and direct observation to collect data on demographics; behaviors; oral hygiene habits; the sum of decayed, missing or filled teeth (DMFT score); oral mucosa status; lip depigmentation and dental fluorosis via a visual scale. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (95% CI), adjusted for known and suspected ESCC risk factors. During the study period, 300 cases and 300 controls were enrolled. Subjects in the highest tertile of DMFT score (≥7) had an increased risk of ESCC with an adjusted OR of 1.96 (95% CI: 1.16-3.36) compared to those with a DMFT score of 0. Severe dental fluorosis was associated with a statistically nonsignificant increased risk of ESCC (adjusted OR = 2.24, 95% CI: 0.97-5.49) compared to individuals with no fluorosis. Associations with oral mucosa status, lip depigmentation and toothbrushing method and frequency were mostly null or uncertain. Poor oral health, indicated by a higher DMFT score, was associated with increased ESCC risk in Malawi. Dental fluorosis is another possible risk factor in this population, but further evaluation is necessary to clarify any effects of fluorosis on ESCC risk.

Survival After Diagnosis of Esophageal Squamous Cell Carcinoma in Malawi.

PURPOSE: Esophageal cancer (EC) is the second most common cancer in Malawi, with esophageal squamous cell carcinoma (ESCC) representing >90% of all ECs. Despite significant morbidity and mortality, little is known about disease outcomes. In this study, we assess survival after ESCC diagnosis in Malawi. METHODS: We report on ESCC cases enrolled in a case-control study at Kamuzu Central Hospital in Lilongwe from August 2017 to April 2020. Suspected cases completed a questionnaire interview; provided blood, urine, and saliva specimens; and underwent a tumor biopsy for histologic confirmation. Cases were followed up by phone biweekly from enrollment to the study end date (December 31, 2020), date of death, or loss to follow-up. Survival was assessed using Kaplan-Meier analysis with the log-rank test. We also examined associations between treatment and ESCC mortality using Cox regression models. RESULTS: There were 300 patients with ESCC enrolled in this study, of whom 290 (97%) had known vital status at the end of follow-up and 10 (3%) were lost to follow-up. Among the 290 patients, 282 (97%) died during follow-up. The median age at enrollment was 55 years (IQR, 48-66), and the median time to death was 106 days (95% CI, 92 to 127). The 1-year, 2-year, and 3-year survival rates were 11% (95% CI, 8 to 15), 3% (95% CI, 1 to 6), and 0.9% (95% CI, 0.8 to 4), respectively. Palliative chemotherapy significantly improved the overall survival of patients with ESCC (Plog-rank = .038) and was significantly associated with reduced mortality (adjusted hazard ratio, 0.71 [95% CI, 0.51 to 0.99]). No significant association was observed between tobacco use, alcohol consumption, or HIV status and mortality. CONCLUSION: Survival after diagnosis of ESCC was poor in Malawi. Although palliative chemotherapy was associated with improved survival, prevention and earlier detection remain key priorities to improve ESCC mortality at a population level.

A Genomic Analysis of Esophageal Squamous Cell Carcinoma in Eastern Africa.

BACKGROUND: Esophageal squamous cell carcinoma (ESCC) comprises 90% of all esophageal cancer cases globally and is the most common histology in low-resource settings. Eastern Africa has a disproportionately high incidence of ESCC. METHODS: We describe the genomic profiles of 61 ESCC cases from Tanzania and compare them to profiles from an existing cohort of ESCC cases from Malawi. We also provide a comparison to ESCC tumors in The Cancer Genome Atlas (TCGA). RESULTS: We observed substantial transcriptional overlap with other squamous histologies via comparison with TCGA PanCan dataset. DNA analysis revealed known mutational patterns, both genome-wide as well as in genes known to be commonly mutated in ESCC. TP53 mutations were the most common somatic mutation in tumors from both Tanzania and Malawi but were detected at lower frequencies than previously reported in ESCC cases from other settings. In a combined analysis, two unique transcriptional clusters were identified: a proliferative/epithelial cluster and an invasive/migrative/mesenchymal cluster. Mutational signature analysis of the Tanzanian cohort revealed common signatures associated with aging and cytidine deaminase activity (APOBEC) and an absence of signature 29, which was previously reported in the Malawi cohort. CONCLUSIONS: This study defines the molecular characteristics of ESCC in Tanzania, and enriches the Eastern African dataset, with findings of overall similarities but also some heterogeneity across two unique sites. IMPACT: Despite a high burden of ESCC in Eastern Africa, investigations into the genomics in this region are nascent. This represents the largest comprehensive genomic analysis ESCC from sub-Saharan Africa to date.

Sex-Based Differences in Survival Among Patients with Acute Abdomen Undergoing Surgery in Malawi: A Propensity Weighted Analysis.

INTRODUCTION: Sex disparities in access to health care in low-resource settings have been demonstrated. Still, there has been little research on the effect of sex on postoperative outcomes. We evaluated the relationship between sex and mortality after emergency abdominal surgery. METHODS: We performed a retrospective cohort study using the acute care surgery database at Kamuzu Central Hospital (KCH) in Malawi. We included patients who underwent emergency abdominal surgery between 2013 and 2021. We created a propensity score weighted Cox proportional hazards model to assess the relationship between sex and inpatient survival. RESULTS: We included 2052 patients in the study, and 76% were males. The most common admission diagnosis in both groups was bowel obstruction. Females had a higher admission shock index than males (0.91 vs. 0.81, p < 0.001) and a longer delay from admission until surgery (1.47 vs. 0.79 days, p < 0.001). Females and males had similar crude postoperative mortality (16.3% vs. 15.3%, p = 0.621). The final Cox proportional hazards regression model was based on the propensity-weighted cohort. The mortality hazard ratio was 0.65 among females compared to males (95% CI 0.46-0.92, p = 0.014). CONCLUSIONS: Our results show a survival advantage among female patients undergoing emergency abdominal surgery despite sex-based disparities in access to surgical care that favors males. Further research is needed to understand the mechanisms underlying these findings.

Chest Trauma Management in Low- and Middle-Income Countries.

Trauma is a leading cause of death and disability worldwide and disproportionately affects those in low- and middle-income countries (LMICs). Globally, two-thirds of injured patients sustain trauma to the thoracic cavity. Further research, capacity building, and increased awareness are needed to limit the high thoracic trauma-associated morbidity and mortality in LMICs.

An international report on bacterial communities in esophageal squamous cell carcinoma.

The incidence of esophageal squamous cell carcinoma (ESCC) is disproportionately high in the eastern corridor of Africa and parts of Asia. Emerging research has identified a potential association between poor oral health and ESCC. One possible link between poor oral health and ESCC involves the alteration of the microbiome. We performed an integrated analysis of four independent sequencing efforts of ESCC tumors from patients from high- and low-incidence regions of the world. Using whole genome sequencing (WGS) and RNA sequencing (RNAseq) of ESCC tumors from 61 patients in Tanzania, we identified a community of bacteria, including members of the genera Fusobacterium, Selenomonas, Prevotella, Streptococcus, Porphyromonas, Veillonella and Campylobacter, present at high abundance in ESCC tumors. We then characterized the microbiome of 238 ESCC tumor specimens collected in two additional independent sequencing efforts consisting of patients from other high-ESCC incidence regions (Tanzania, Malawi, Kenya, Iran, China). This analysis revealed similar ESCC-associated bacterial communities in these cancers. Because these genera are traditionally considered members of the oral microbiota, we next explored whether there was a relationship between the synchronous saliva and tumor microbiomes of ESCC patients in Tanzania. Comparative analyses revealed that paired saliva and tumor microbiomes were significantly similar with a specific enrichment of Fusobacterium and Prevotella in the tumor microbiome. Together, these data indicate that cancer-associated oral bacteria are associated with ESCC tumors at the time of diagnosis and support a model in which oral bacteria are present in high abundance in both saliva and tumors of some ESCC patients.

Inter-hospital Transfer Delays to a Tertiary Referral Center and Postoperative Outcomes in Patients with Abdominal Surgical Emergencies in Malawi.

BACKGROUND: In low-income countries (LICs), patients with abdominal surgical emergencies often initially present to primary or district hospitals and are transferred to referral hospitals for surgical management. The transfer process introduces a delay to care, but the relationship between transfer time and outcomes has not been studied in LICs. We sought to evaluate the effect of transfer delays on postoperative outcomes among patients undergoing emergency abdominal surgery in Malawi. METHODS: This is a retrospective analysis of the acute care surgery database at Kamuzu Central Hospital (KCH), a referral hospital in Malawi. Patients were eligible for inclusion if transferred from another facility to KCH for emergency abdominal surgery. We used logistic regression modeling to evaluate the relationship between transfer time and postoperative complications and mortality. RESULTS: The study included 2037 patients. Female patients, patients transferred from district hospitals, and patients with bowel obstructions were most likely to spend over three days at a referring facility before transfer. On regression modeling, each additional day until transfer was associated with an 18% increase in odds of developing a postoperative complication (OR 1.18, 95% CI 1.05-1.31, p = 0.005) and a 19% increase in odds of postoperative mortality (OR 1.19, 95% CI 1.08-1.31, p < 0.001). CONCLUSION: Among patients requiring emergency abdominal surgery in Malawi, transfer delays are associated with higher postoperative complications and mortality rates. Further research should focus on identifying the factors causing delays so that interventions aimed at improving the transfer process can be developed.

Treatment outcomes of esophageal cancer in Eastern Africa: protocol of a multi-center, prospective, observational, open cohort study.

BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is a major cause of cancer morbidity and mortality in Eastern Africa. The majority of patients with ESCC in Eastern Africa present with advanced disease at the time of diagnosis. Several palliative interventions for ESCC are currently in use within the region, including chemotherapy, radiation therapy with and without chemotherapy, and esophageal stenting with self-expandable metallic stents; however, the comparative effectiveness of these interventions in a low resource setting has yet to be examined. METHODS: This prospective, observational, multi-center, open cohort study aims to describe the therapeutic landscape of ESCC in Eastern Africa and investigate the outcomes of different treatment strategies within the region. The 4.5-year study will recruit at a total of six sites in Kenya, Malawi and Tanzania (Ocean Road Cancer Institute and Muhimbili National Hospital in Dar es Salaam, Tanzania; Kilimanjaro Christian Medical Center in Moshi, Tanzania; Tenwek Hospital in Bomet, Kenya; Moi Teaching and Referral Hospital in Eldoret, Kenya; and Kamuzu Central Hospital in Lilongwe, Malawi). Treatment outcomes that will be evaluated include overall survival, quality of life (QOL) and safety. All patients (≥18 years old) who present to participating sites with a histopathologically-confirmed or presumptive clinical diagnosis of ESCC based on endoscopy or barium swallow will be recruited to participate. Key clinical and treatment-related data including standardized QOL metrics will be collected at study enrollment, 1 month following treatment, 3 months following treatment, and thereafter at 3-month intervals until death. Vital status and QOL data will be collected through mobile phone outreach. DISCUSSION: This study will be the first study to prospectively compare ESCC treatment strategies in Eastern Africa, and the first to investigate QOL benefits associated with different treatments in sub-Saharan Africa. Findings from this study will help define optimal management strategies for ESCC in Eastern Africa and other resource-limited settings and will serve as a benchmark for future research. TRIAL REGISTRATION: This study was retrospectively registered with the ClinicalTrials.gov database on December 15, 2021,  NCT05177393 .

Tobacco and other risk factors for esophageal squamous cell carcinoma in Lilongwe Malawi: Results from the Lilongwe esophageal cancer case: Control study.

OBJECTIVE: Esophageal cancer is the second commonest cancer in Malawi, and 95% of all cases are esophageal squamous cell carcinoma (ESCC). Very little is known about the epidemiology of ESCC in Malawi including risk factors. The main objective of the study was to evaluate and describe risk factors of ESCC in Malawi. METHODS: We conducted a case-control study from 2017 to 2020 at two hospitals in Lilongwe, Malawi and consenting adults were eligible for inclusion. Endoscopy was conducted on all cases and biopsies were obtained for histological confirmation. Controls were selected from patients or their guardians in orthopedic, dental and ophthalmology wards and they were frequency matched by sex, age, and region of origin to cases. An electronic structured questionnaire was delivered by a trained interviewer. Multivariate conditional logistic regression models were used to assess the associations between subject characteristics, habits, and medical history and risk of ESCC. RESULTS: During the study period, 300 cases and 300 controls were enrolled into the study. Median age of cases and controls was 56 years and 62% of the cases were male. Among cases, 30% were ever cigarette smokers as were 22% of controls. Smoking cigarettes had an adjusted odds ratio of 2.4 (95% CI 1.4-4.2 p = 0.003). HIV+ status was present in 11% of cases and 4% controls, which resulted in an adjusted odds ratio was 4.0 (95% CI 1.8-9.0 p = 0.001). Drinking hot tea was associated with an adjusted odd ratio of 2.9 (95% CI 1.3-6.3 p = 0.007). Mold on stored grain has an adjusted odd ratio of 1.6 (95% CI 1.1-2.5 p = 0.021). CONCLUSION: Reducing smoking cigarettes, consumption of scalding hot tea, and consumption of contaminated grain, could potentially help reduce the burden of ESCC in Malawi. Further investigation of the association between HIV status and ESCC are warranted.

Improving Access to Self-Expanding Metal Stents for Patients With Esophageal Cancer in Eastern Africa: A Stepwise Implementation Strategy.

PURPOSE: The eastern corridor of Africa is affected by a high burden of esophageal cancer (EC), with > 90% of patients presenting with advanced disease. Self-expanding metal stents (SEMS) have been previously reported as safe and effective for palliation of malignant dysphagia in resource-limited settings; however, access is limited throughout Eastern Africa. METHODS: In response to demand for palliative interventions for patients with dysphagia because of EC, the African Esophageal Cancer Consortium (AfrECC) partnered with the Clinton Health Access Initiative to improve access to SEMS in Eastern Africa. We undertook a stepwise implementation approach to (1) identify barriers to SEMS access, (2) conduct a market analysis, (3) select an industry partner, (4) establish regulatory and procurement processes, (5) develop endoscopic training resources, (6) create a medical device registry, and (7) establish principles of accountability. RESULTS: Following an evaluation of market demand and potential SEMS manufacturers, Boston Scientific Corporation announced its commitment to launch an access program to provide esophageal SEMS to patients in Tanzania, Kenya, Malawi, and Zambia at a subsidized price. Parallel regulatory and procurement processes were established in each participating country. Endoscopy training courses were designed and conducted, using the Training-of-Trainers model. A device registry was created to centralize data for quality control and to monitor channels of SEMS distribution. Principles of accountability were developed to guide the sustainability of this endeavor. CONCLUSION: The AfrECC Stent Access Initiative is an example of a multisector partnership formed to provide an innovative solution to align regional needs with a supply chain for a high-priority medical device.

Police Transportation Following Vehicular Trauma and Risk of Mortality in a Resource-Limited Setting.

BACKGROUND: In resource-limited settings, prehospital trauma care and transportation from the scene to a hospital is not well developed. Critically injured patients present to the hospital via privately owned vehicles (PV), public transportation, or the police. We aimed to determine the mortality following road traffic injury based on the mode of transportation to our trauma center. METHODS: We performed a retrospective analysis of the Kamuzu Central Hospital (KCH) Trauma Registry from January 2011 to May 2018. Patients with road traffic injuries, presenting from the scene, were included. Those brought in dead or discharged from casualty were excluded. Bivariate analysis was performed over mortality. A Poisson multivariate regression determined the relative risk of mortality by prehospital transportation. RESULTS: 2853 patients were included; 7.8% (n = 223) died. Patients were transported by PV (n = 1963, 68.8%), minibus (n = 497, 17.4%), and police (268, 9.4%). No patients were transported by ambulance. Patients transported by police (1 h, IQR 0-2) and PV (1 h, IQR 0-2), arrived earlier than those transported by minibus (2 h, IQR 0-27), p < 0.001. There was no difference in injury severity between the transportation cohorts. Compared to PV, patients transported by police (RR 1.56, 95% CI 1.13-2.17, p = 0.008) have an increased risk of mortality after controlling for injury severity. There was no difference in mortality in patients presenting by minibus (RR 0.83, 95% CI 0.55-1.24, p = 0.4). CONCLUSION: Patients transported to KCH via police have a higher risk of mortality than those transported via private vehicle after controlling for injury severity. Training police in basic life support may be an initial target of intervention in reducing trauma mortality. Overall, the creation of a functional prehospital ambulance system with a cadre of paramedics is necessary for both trauma and non-trauma patients alike. This can only be achieved by training all stakeholders, the police, public transport drivers, and the public at large.

Epidemiological Comparisons and Risk Factors for Pre-hospital and In-Hospital Mortality Following Traumatic Injury in Malawi.

BACKGROUND: In sub-Saharan Africa, trauma is a leading cause of mortality in people less than 45 years. Injury mechanism and cause of death are difficult to characterize in the absence of pre-hospital care and a trauma surveillance database. Pre-hospital deaths (PHD) and in-hospital deaths (IHD) of trauma patient were compared to elucidate comprehensive injury characteristics associated with mortality. METHODS: A retrospective, descriptive analysis of adults (≥ 13 years) presenting to Kamuzu Central Hospital in Lilongwe, Malawi, from February 2008 to May 2018 was performed. Utilizing an emergency department-based trauma surveillance database, univariate and bivariate analysis was performed to compare patient and injury characteristics of pre-hospital and in-hospital deaths. A Poisson multivariate regression was performed, predicting the relative risk of PHD. RESULTS: Between February 2008 and May 2018, 131,020 adult trauma patients presented to KCH, with 2007 fatalities. Of those patients, 1130 (56.3%) and 877 (43.7%) were PHD and IHD, respectively. The majority were men, with a mean age of 33.4 years (SD 12.1) for PHD and 37.4 years (SD 15.5) for IHD, (p < 0.001). Head injuries (n = 545, 49.2% vs. n = 435, 49.7%) due to assaults (n = 255, 24.7% vs. n = 178, 21.8%) and motor vehicle collisions (MVC) (n = 188, 18.2% vs. n = 173, 21.2%) were the leading cause of both groups (PHD vs. IHD). Transportation to the hospital was primarily police (n = 663, 60.1%) for PHD and ambulance (n = 401, 46.4%) for IHD. Patients who were transported to KCH by the police (RR 1.97, 95% 1.52-2.55, p < 0.001) when compared to transport via minibus had an increased relative risk of PHD. Patients with a head or spine (RR 1.32, 95% CI 1.34-1.53, p < 0.001), chest (RR 1.34, 95% CI 1.11-1.62, p = 0.002) or abdomen and pelvis (RR 1.30, 95% CI 1.14-1.53, p = 0.004) when compared to extremity injury had an increased relative risk of PHD. CONCLUSIONS: Head injury from assaults and MVC is the leading cause of PHD and IHD in Malawi. The majority of patients are transported via police if PHD. Of IHD patients, the majority are transported by ambulance, most often from outside hospitals. Both are consistent with the absence of a pre-hospital system in Malawi. Improving pre-hospital care, with a particular focus on head injury and strategies for vehicular injury prevention within a trauma system, will reduce adult trauma mortality in Malawi.

Secondary Overtriage of Trauma Patients to a Central Hospital in Malawi.

INTRODUCTION: Secondary overtriage (OT) is the unnecessary transfer of injured patients between facilities. In low- and middle-income countries (LMICs), which shoulder the greatest burden of trauma globally, the impact of wasted resources on an overburdened system is high. This study determined the rate and associated characteristics of OT at a Malawian central hospital. METHODS: A retrospective analysis of prospectively collected data from January 2012 through July 2017 was performed at Kamuzu Central Hospital (KCH) in Lilongwe, Malawi. Patients were considered OT if they were discharged alive within 48 h without undergoing a procedure, and were not severely injured or in shock on arrival. Factors evaluated for association with OT included patient demographics, injury characteristics, and transferring facility information. RESULTS: Of 80,915 KCH trauma patients, 15,422 (19.1%) transferred from another facility. Of these, 8703 (56.2%) were OT. OT patients were younger (median 15, IQR: 6-31 versus median 26, IQR: 11-38, p < 0.001). Patients with primary extremity injury (5308, 59.9%) were overtriaged more than those with head injury (1991, 51.8%) or torso trauma (1349, 50.8%), p < 0.001. The OT rate was lower at night (18.9% v 28.7%, p < 0.001) and similar on weekends (20.4% v 21.8%, p = 0.03). OT was highest for penetrating wounds, bites, and falls; burns were the lowest. In multivariable modeling, risk of OT was greatest for burns and soft tissue injuries. CONCLUSIONS: The majority of trauma patients who transfer to KCH are overtriaged. Implementation of transfer criteria, trauma protocols, and interhospital communication can mitigate the strain of OT in resource-limited settings.

The role of endoscopy after upper gastrointestinal bleeding in sub-Saharan Africa: A prospective observational cohort study.

Background: Upper gastrointestinal (UGI) bleed is a common surgical disease in sub-Saharan Africa where there is often a lack of diagnostic and interventional adjuncts such as endoscopy. This study sought to characterize the role of endoscopy in management of acute UGI bleeding. Materials and Methods: This is a prospective observational analysis of adults presenting with an UGI bleed to a tertiary center in Lilongwe, Malawi, over two years. Patients were classified as having no endoscopy, diagnostic endoscopy, or endoscopy with variceal banding. Bivariate, survival analysis, and logistic regression analyses were used to compare intervention cohorts. Results: 293 patients were included with 49 patients (16.7%) receiving endoscopy with banding, 65 (22.2%) patients receiving diagnostic endoscopy only, and 179 (61.1%) receiving no endoscopy. Upon survival analysis comparing to the no endoscopy group, cox hazard modelling showed an adjusted hazard ratio over 30 days of 0.12 (95% CI 0.02, 0.88, p=0.038) for the endoscopic banding group and a hazard ratio of 0.39 (95% CI 0.13, 1.16, p=0.090) for the diagnostic endoscopy only group. Physical exam findings consistent with cirrhosis and decreasing age were independent predictors of an endoscopic diagnosis of variceal bleeding. Conclusion: Esophagogastric varices are a common cause of UGI bleeding in sub-Saharan Africa and can be predicted with age and physical exam findings. Endoscopy with variceal banding has a survival benefit for patients presenting with acute UGI bleed even with relatively low utilization. Appropriately triaging patients with likely variceal bleeding and improving endoscopy capacity would likely have a significant impact on mortality.

The African Esophageal Cancer Consortium: A Call to Action.

Esophageal cancer is the eighth most common cancer worldwide and the sixth most common cause of cancer-related death; however, worldwide incidence and mortality rates do not reflect the geographic variations in the occurrence of this disease. In recent years, increased attention has been focused on the high incidence of esophageal squamous cell carcinoma (ESCC) throughout the eastern corridor of Africa, extending from Ethiopia to South Africa. Nascent investigations are underway at a number of sites throughout the region in an effort to improve our understanding of the etiology behind the high incidence of ESCC in this region. In 2017, these sites established the African Esophageal Cancer Consortium. Here, we summarize the priorities of this newly established consortium: to implement coordinated multisite investigations into etiology and identify targets for primary prevention; to address the impact of the clinical burden of ESCC via capacity building and shared resources in treatment and palliative care; and to heighten awareness of ESCC among physicians, at-risk populations, policy makers, and funding agencies.

Interpersonal violence in peacetime Malawi.

BACKGROUND: The contribution of interpersonal violence (IPV) to trauma burden varies greatly by region. The high rates of IPV in sub-Saharan Africa are thought to relate in part to the high rates of collective violence. Malawi, a country with no history of internal collective violence, provides an excellent setting to evaluate whether collective violence drives the high rates of IPV in this region. METHODS: This is a retrospective review of a prospective trauma registry from 2009 through 2016 at Kamuzu Central Hospital in Lilongwe, Malawi. Adult (>16 years) victims of IPV were compared with non-intentional trauma victims. Log binomial regression determined factors associated with increased risk of mortality for victims of IPV. RESULTS: Of 72 488 trauma patients, 25 008 (34.5%) suffered IPV. Victims of IPV were more often male (80.2% vs. 74.8%; p<0.001), younger (median age: 28 years (IQR: 23-34) vs. 30 years (IQR: 24-39); p<0.001), and were more often admitted at night (47.4% vs. 31.9%; p<0.001). Of the IPV victims, 16.5% admitted alcohol use, compared with only 4.4% in other trauma victims (p<0.001). In regression modeling, compared with extremity injuries, head injuries (3.14, 2.24-4.39; p<0.001) and torso injuries (4.32, 2.98-6.27; p<0.001) had increased risk of mortality. Compared with other or unknown mechanisms, penetrating injuries also had increased risk of mortality (1.46, 95% CI 1.17 to 1.81, p=0.001). Alcohol use was associated with a lower risk of mortality (0.54, 95% CI 0.39 to 0.75; p<0.001). DISCUSSION: Even in a sub-Saharan country that never experienced internal collective violence, IPV injury rates are high. Public health efforts to measure and address alcohol use, and studies to determine the role of "mob justice," poverty, and intimate partner violence in IPV, in Malawi are needed. LEVEL OF EVIDENCE: Level III.

Outcomes Following Exploratory Burr Holes for Traumatic Brain Injury in a Resource Poor Setting.

BACKGROUND: Traumatic brain injury (TBI) is a leading cause of death and disability worldwide. The incidence of TBI in low- and middle-income countries (LMICs) is disproportionately high, with an associated increased risk of mortality from TBI relative to high-income countries. Although computed tomography is the diagnostic method of choice, this is often unavailable in LMICs. Exploratory burr holes may provide a suitable choice for diagnosis and treatment of TBI. METHODS: We performed a retrospective review of prospectively collected data at KCH, a tertiary care center in Lilongwe, Malawi. All trauma patients presenting between June 2012 and July 2015 with a deteriorating level of consciousness and localizing signs and who underwent exploratory burr holes were included. Additionally, we included all patients admitted with TBI, requiring higher-level care during 2011. No patients underwent exploratory burr hole during this time. We performed logistic regression to identify predictors of mortality in the total population of TBI patients. RESULTS: Among the 241 patients who presented to KCH with TBI requiring higher-level care, the total mortality was 16.4%. More than half (163, or 68%) underwent exploratory burr hole with a mortality of 6.8%. Mortality in patients who did not undergo exploratory burr hole was 43.9%. Upon adjusted logistic regression, not undergoing exploratory burr hole significantly increased the odds of mortality (odds ratio = 12.0, P = 0.000, 95% confidence interval = 4.48-31.9). CONCLUSION: Exploratory burr holes remain an important diagnostic and therapeutic procedure for TBI in LMICs. Exploratory burr hole technique should be integrated into general surgery education to attenuate TBI-related mortality.

Subtyping sub-Saharan esophageal squamous cell carcinoma by comprehensive molecular analysis.

Esophageal squamous cell carcinoma (ESCC) is endemic in regions of sub-Saharan Africa (SSA), where it is the third most common cancer. Here, we describe whole-exome tumor/normal sequencing and RNA transcriptomic analysis of 59 patients with ESCC in Malawi. We observed similar genetic aberrations as reported in Asian and North American cohorts, including mutations of TP53, CDKN2A, NFE2L2, CHEK2, NOTCH1, FAT1, and FBXW7. Analyses for nonhuman sequences did not reveal evidence for infection with HPV or other occult pathogens. Mutational signature analysis revealed common signatures associated with aging, cytidine deaminase activity (APOBEC), and a third signature of unknown origin, but signatures of inhaled tobacco use, aflatoxin and mismatch repair were notably absent. Based on RNA expression analysis, ESCC could be divided into 3 distinct subtypes, which were distinguished by their expression of cell cycle and neural transcripts. This study demonstrates discrete subtypes of ESCC in SSA, and suggests that the endemic nature of this disease reflects exposure to a carcinogen other than tobacco and oncogenic viruses.

Development of a ratio of emergent to total hernia repairs as a surgical capacity metric.

INTRODUCTION: Non-communicable diseases including surgical conditions are gaining attention in developing countries. Despite this there are few metrics for surgical capacity. We hypothesized that (a) the ratio of emergent to total hernia repairs (E/TH) would correlate with per capita health care expenditures for any given country, and (b) the E/TH is easy to obtain in resource-poor settings. METHODS: We performed a systematic review to identify the E/TH for as many countries as possible (Prospero registry CRD42013004645). We screened 1285 English language publications since 1990; 23 met inclusion criteria. Primary data was also collected from Kamuzu Central Hospital (KCH) in Lilongwe, Malawi. A total of 13 countries were represented. Regression analysis was used to determine the correlation between per capita health care spending and the E/TH. RESULTS: There is a strong correlation between the log values of the ratio emergent to total groin hernias and the per capita health care spending that is robust across country income levels (R(2) = 0.823). Primary data from KCH was easily obtained and demonstrated a similar correlation. CONCLUSIONS: The ratio of emergent to total groin hernias is a potential measure of surgical capacity using data that is easily attainable. Further studies should validate this metric against other accepted health care capacity indicators. Systematic review registered with Prospero (CRD42013004645).