Differential prognostic value of residual nodal burden in breast cancer subtypes.

PURPOSE: Residual cancer burden (RCB) index after neoadjuvant chemotherapy (NAC) is highly prognostic in patients with breast cancer (BC) but does not account for subtype or the precise impact of residual nodal burden (RNB). We aimed to precisely define the effect of RNB on survival by subtypes. METHODS: Adult women with non-metastatic BC diagnosed from 2006 to 2021 in the National Cancer Database (NCDB) who received NAC followed by surgery within 8 months were included. RNB was also evaluated as a predictor of mortality with multivariable logistic regression. Kaplan-Meier analyses were performed to compare overall survival. RESULTS: 51,917 patients were included. After adjustment, ypN stage was the strongest predictor of mortality, with an odds ratio (OR) of 2.24 (95% CI 2.08-2.41) for ypN1 vs ypN0 and increased with increasing nodal burden-ypN2 vs ypN0 OR 5.03, 95% CI 4.60-5.51 and ypN3 vs ypN0 OR 8.85, 95% CI 7.88-9.93. Stratification of survival curves with higher RNB is most pronounced for triple-negative breast cancer (TNBC) with an absolute difference of 64% in 5-year overall survival between ypN0 and ypN3 patients, and lowest for the ER+/HER2- subtype with a 25% absolute difference in 5-year OS between ypN0 and ypN3 patients. On interaction analysis, ypN status was a stronger predictor of mortality for the TNBC subtype compared to other subtypes. CONCLUSION: RNB has a significantly different impact on survival by BC subtypes. Future study of optimal therapeutic strategies for patients with residual nodal disease after NAC should account for subtype-specific differences in prognosis.

Nodal Response and Survival After Neoadjuvant Endocrine Therapy in Hormone Receptor-Positive Breast Cancer: 20-Year Experience from a Single Institution.

INTRODUCTION: Axillary response to neoadjuvant endocrine therapy (NET) for the treatment of hormone receptor-positive breast cancer (HR+ BC) is not well-described. This study was designed to characterize nodal response after NET. METHODS: Patients receiving NET followed by curative intent surgery at a comprehensive cancer center from 1998 to 2022 in a prospectively collected registry were included. Patients with distant metastasis were excluded. Primary outcome was nodal pathologic complete response (pCR). Downstaging was defined as post-NET decrease in category. RESULTS: We included 123 patients; the majority were cT2 (n = 59) or cT3 (n = 35), and cN0 (n = 81). Median age was 70.0 years (interquartile range 62.1-76.0). Forty-two patients (34.1%) were clinically node-positive. After NET, 73 (59.8%) underwent breast-conserving surgery. All patients underwent sentinel lymph node biopsy, and 12 (9.8%) underwent completion axillary lymph node dissection. In-breast downstaging was achieved in 51 (41.5%) patients, 1 (0.8%) had breast pCR, and 14 (11.4%) had breast upstaging. Axillary downstaging was achieved in 10 (23.8%), 6 patients (14.3%) had nodal pCR, and 14 (33.3%) had axillary upstaging. At 10-year follow-up, local recurrence was 1% and distant recurrence was 14%, while disease-free survival was 82%. After adjusting for demographic and clinical factors, age was the only characteristic associated with mortality (hazard ratio 1.07, 95% confidence interval 1.01-1.13). CONCLUSIONS: In HR+ BC treated with NET, long-term disease-free survival is good, although nodal pCR is uncommon for cN+ patients. Future studies are needed to elucidate optimal neoadjuvant systemic therapy and to delineate oncologically safe strategies to deescalate axillary management for residual microscopic disease.

Transfusion and Mortality in Acute Care Surgical Patients in Malawi: A Propensity-Matched Analysis.

INTRODUCTION: Information on transfusion-associated outcomes is limited in sub-Saharan Africa. We sought to characterize predictors of mortality in transfused patients with acute care surgical conditions in Malawi. METHODS: We performed a retrospective propensity-matched analysis of patients with acute care surgical conditions at Kamuzu Central Hospital in Malawi from 2013 to 2021. We compared outcomes between patients who did and did not receive transfusions. RESULTS: A total of 7395 patients were included. Transfused patients (n = 1086) were older (median 43 y with interquartile range 30-59, versus 39 y [interquartile range 27-53] in the nontransfused group, P < 0.01), had a higher proportion of females (41% versus 27%, P < 0.01), presented earlier to the hospital (median 2.9 versus 3.7 d, P = 0.02), and with lower hemoglobin levels (27% versus 1% < 7 g/dL, P < 0.01). They had a lower rate of surgical intervention (48% versus 59%, P < 0.01) but a higher rate of complications (62% versus 33%, P < 0.01). Crude in-hospital mortality was 25.5% for the transfused group and 12.8% for the nontransfused group (P < 0.01). After propensity matching, transfused patients had three times the odds of mortality compared to nontransfused patients (odds ratio 3.3, 95% confidence interval 2.3, 4.8). CONCLUSIONS: In this propensity-matched study, transfused surgical patients were more likely to experience in-hospital mortality. These results suggest that the transfusion requirement reflects critical illness and warrants further investigation in this low-resource setting.

Predictors of Functional Decline Among Critically Ill Surgical Patients: A National Analysis.

INTRODUCTION: Functional decline is associated with critical illness, though this relationship in surgical patients is unclear. This study aims to characterize functional decline after intensive care unit (ICU) admission among surgical patients. METHODS: We performed a retrospective analysis of surgical patients admitted to the ICU in the Cerner Acute Physiology and Chronic Health Evaluation database, which includes 236 hospitals, from 2007 to 2017. Patients with and without functional decline were compared. Predictors of decline were modeled. RESULTS: A total of 52,838 patients were included; 19,310 (36.5%) experienced a functional decline. Median ages of the decline and nondecline groups were 69 (interquartile range 59-78) and 63 (interquartile range 52-72) years, respectively (P < 0.01). The nondecline group had a larger proportion of males (59.1% versus 55.3% in the decline group, P < 0.01). After controlling for sociodemographic covariates, comorbidities, and disease severity upon ICU admission, patients undergoing pulmonary (odds ratio [OR] 6.54, 95% confidence interval [CI] 2.67-16.02), musculoskeletal (OR 4.13, CI 3.51-4.87), neurological (OR 2.67, CI 2.39-2.98), gastrointestinal (OR 1.61, CI 1.38-1.88), and skin and soft tissue (OR 1.35, CI 1.08-1.68) compared to cardiovascular surgeries had increased odds of decline. CONCLUSIONS: More than one in three critically ill surgical patients experienced a functional decline. Pulmonary, musculoskeletal, and neurological procedures conferred the greatest risk. Additional resources should be targeted toward the rehabilitation of these patients.

The Bidirectionality of Global Surgical Research: The Utility of the Malawi Trauma Score in the United States Trauma Population.

INTRODUCTION: Trauma scoring systems provide valuable risk stratification of injured patients. Trauma scoring systems developed in resource-limited settings, such as the Malawi Trauma Score (MTS), are based on readily available clinical information. This study sought to test the performance of the MTS in a United States trauma population. MATERIALS AND METHODS: We analyzed the United States National Trauma Data Bank during 2017-2020. MTS uses alertness score: alert, responds to verbal or painful stimuli, or unresponsive (AVPU), age, sex, presence of a radial pulse, and primary anatomic injury location. MTS and an age-adjusted version reflective of the US age distribution, was evaluated for its performance in predicting crude mortality in the National Trauma Data Bank using receiver operating characteristic analysis. We utilized logistic regression to model the odds ratio of death at a particular MTS cutoff. RESULTS: A total of 3,833,929 patients were included. The mean age was 49.3 y (sandard deviation 24.4), with a male preponderance (61.1%). Crude mortality was 3.4% (n = 131,452/3,833,929). The area under the curve for the MTS in predicting mortality was 0.87 (95% CI 0.87, 0.88). The area under the curve for a cutoff of 15 was 0.83 (95% CI 0.83, 0.83). An MTS of 15 higher had an odds ratio of death of 46.5 (95% CI 45.9, 47.1), compared to those with a score of 14 or lower. CONCLUSIONS: MTS has excellent performance as a predictor of mortality in a US trauma population. MTS is simple to calculate and can be estimated in the prehospital setting or the emergency department. Consequently, it may have utility as a triage tool in both high-income trauma systems and resource-limited settings.

Fall-Related Injuries in Malawi: Outcomes and Trends Over Time.

BACKGROUND: Fall-related injury (FRI) is a leading cause of injuries worldwide. Data on injury patterns and trends over time are lacking in resource-limited settings. METHODS: We performed a retrospective analysis of FRI at Kamuzu Central Hospital in Malawi from 2009 to 2021. Outcomes were compared between patients presenting with FRI and those with other injury mechanisms. Bivariate and multivariate regressions were used to determine predictors of presentation following falls and mortality. We also analyzed time trends. RESULTS: A total of 166,047 patients were included, of which 41,695 were patients presenting after falls (25.7%). Most FRI patients were between 5 and 45 (67.2%) and male (66.9%). Most falls occurred at home (67.3%) and resulted in extremity injuries (51.6%). The predicted probability of hospital presentation after falling is highest for children ≤ 5 years and adults > 60 years and decreases over time. On multivariate analysis, patients between 5 and 15 [adjusted odds ratio (AOR) 1.70, 95% confidence interval (CI) 1.63-1.77] and > 60 (AOR 1.14, 95% CI 1.07-1.22) and women (AOR 1.13, 95% CI 1.10-1.16) are more likely to present with FRI. Compared to patients with non-FRI, those with FRI were more likely to have been injured at school (AOR 2.16, 95% CI 2.01-2.32) and during sports and recreation (AOR 4.53, 95% CI 4.24-4.85). CONCLUSION: FRI is the most common injury presentation after motor vehicle injury in this low-resource setting. This study provides essential information about FRI in Malawi over time. Our findings can help inform resource allocation and injury prevention initiatives.

Tri-modal Distribution of Trauma Deaths in a Resource-Limited Setting: Perception Versus Reality.

BACKGROUND: Advances in trauma care in high-income countries have significantly reduced late deaths following trauma, challenging the classical trimodal pattern of trauma-associated mortality. While studies from low and middle-income countries have demonstrated that the trimodal pattern is still occurring in many regions, there is a lack of data from sub-Saharan Africa evaluating the temporal epidemiology of trauma deaths. METHODS: We conducted a retrospective analysis of the trauma registry at Kamuzu Central Hospital in Lilongwe, Malawi, including all injured patients presenting to the emergency department (ED) from 2009 to 2021. Patients were compared based on timing of death relative to time of injury. We then used a modified Poisson regression model to identify adjusted predictors for early mortality compared to late mortality. RESULTS: Crude mortality of patients presenting to the ED in the study period was 2.4% (n = 4,096/165,324). Most patients experienced a pre-hospital death (n = 2,330, 56.9%), followed by death in the ED (n = 619, 15.1%). Early death (pre-hospital or ED) was associated with transportation by police (RR1.52, 95% CI 1.38, 1.68) or private vehicle (RR1.20, 95% CI 1.07, 1.31), vehicle-related trauma (RR1.10, 95% CI 1.05, 1.14), and penetrating injury (RR1.11, 95% CI 1.04, 1.19). Ambulance transportation was associated with a 40% decrease in the risk of early death. CONCLUSIONS: At a busy tertiary trauma center in Malawi, most trauma-associated deaths occur within 48 h of injury, with most in the pre-hospital setting. To improve clinical outcomes for trauma patients in this environment, substantial investment in pre-hospital care is required through first-responder training and EMS infrastructure.

The Timing of Operative Intervention for Pediatric Burn Patients in Malawi.

BACKGROUND: Defining the optimal timing of operative intervention for pediatric burn patients in a resource-limited environment is challenging. We sought to characterize the association between mortality and the timing of operative intervention at a burn center in Lilongwe, Malawi. METHODS: This is a retrospective analysis of burn patients (<18 years old) presenting to Kamuzu Central Hospital from 2011 to 2022. We compared patients who underwent excision and/or burn grafting based on the timing of the operation. We used logistic regression modeling to estimate the adjusted odds ratio of death based on the timing of surgery. RESULTS: We included 2502 patients with a median age of 3 years (IQR 1-5) and a male preponderance (56.8%). 411 patients (16.4%) had surgery with a median time to surgery of 18 days (IQR 8-34). The crude mortality rate among all patients was 17.0% and 9.1% among the operative cohort. The odds ratio of mortality for patients undergoing surgery within 3 days from presentation was 5.00 (95% CI 2.19, 11.44) after adjusting for age, sex, % total burn surface area (TBSA), and flame burn. The risk was highest for the youngest patients. CONCLUSIONS: Children who underwent burn excision and/or grafting in the first 3 days of hospitalization had a much higher risk of death than patients undergoing surgical intervention later. Delaying operative intervention till >72 h for pediatric patients, especially those under 5 years old, may confer a survival advantage. More investment is needed in early resuscitation and monitoring for this patient population.

Arrhythmias in Critically Ill Surgical and Non-surgical Patients: A National Propensity-Matched Study.

BACKGROUND: Arrhythmias are common in critically ill patients, though the impact of arrhythmias on surgical patients is not well delineated. We aimed to characterize mortality following arrhythmias in critically ill patients. METHODS: We performed a propensity-matched retrospective analysis of intensive care unit (ICU) patients from 2007 to 2017 in the Cerner Acute Physiology and Chronic Health Evaluation database. We compared outcomes between patients with and without arrhythmias and those with and without surgical indications for ICU admission. We also modeled predictors of arrhythmias in surgical patients. RESULTS: 467,951 patients were included; 97,958 (20.9%) were surgical patients. Arrhythmias occurred in 1.4% of the study cohorts. Predictors of arrhythmias in surgical patients included a history of cardiovascular disease (odds ratio [OR] 1.35, 95% confidence interval [CI95] 1.11-1.63), respiratory failure (OR 1.48, CI95 1.12-1.96), pneumonia (OR 3.17, CI95 1.98-5.10), higher bicarbonate level (OR 1.03, CI95 1.01-1.05), lower albumin level (OR 0.79, CI95 0.68-0.91), and vasopressor requirement (OR 27.2, CI95 22.0-33.7). After propensity matching, surgical patients with arrhythmias had a 42% mortality risk reduction compared to non-surgical patients (risk ratio [RR] 0.58, CI 95 0.43-0.79). Predicted probabilities of mortality for surgical patients were lower at all ages. CONCLUSIONS: Surgical patients with arrhythmias are at lower risk of mortality than non-surgical patients. In this propensity-matched analysis, predictors of arrhythmias in critically ill surgical patients included a history of cardiovascular disease, respiratory complications, increased bicarbonate levels, decreased albumin levels, and vasopressor requirement. These findings highlight the differential effect of arrhythmias on different cohorts of critically ill populations.

Sociodemographic and Clinical Predictors of Neoadjuvant Chemotherapy in cT1-T2/N0 HER2-Amplified Breast Cancer.

BACKGROUND: The optimal treatment strategy for small node-negative human epidermal growth factor receptor 2-positive (HER2+) breast cancer remains controversial. Neoadjuvant chemotherapy may risk overtreatment, whereas surgery first fails to identify patients with residual disease in need of escalated adjuvant systemic therapy. We investigated patient characteristics associated with receipt of neoadjuvant chemotherapy. METHODS: Adult women with cT1-T2/N0, HER2+ breast cancer between 2013 and 2017 in the National Cancer Database who underwent surgery within 8 months of diagnosis were included. Patients were classified as receiving neoadjuvant chemotherapy versus a surgery-first approach. We assessed the sociodemographic and clinical predictors of neoadjuvant chemotherapy versus surgery first and associations between neoadjuvant chemotherapy and breast cancer treatments using multivariable regression models. RESULTS: We identified 56,784 women, of whom 12,758 (22%) received neoadjuvant chemotherapy, 29,139 (53%) received adjuvant chemotherapy, 12,907 (24%) received no chemotherapy, and 1980 were missing chemotherapy information. After adjustment, cT2 stage was the strongest predictor of neoadjuvant chemotherapy compared with surgery first. Younger age and later diagnosis year were positively associated with receipt of neoadjuvant chemotherapy. In contrast, hormone receptor positivity, Black race, rural county, and government-funded or no health insurance were inversely associated with neoadjuvant chemotherapy. In multivariable analyses, patients who received neoadjuvant chemotherapy were more likely to have a mastectomy (vs. lumpectomy) and sentinel lymph node biopsy or no nodal surgery (vs. axillary lymph node dissection). Patients who received neoadjuvant chemotherapy were more likely to receive multi-agent (vs. single-agent) chemotherapy than those who received adjuvant chemotherapy. CONCLUSIONS: Substantial differences in the utilization of neoadjuvant chemotherapy exist in women with HER2+ breast cancer, which reflect both clinical parameters and disparities. Optimal treatment strategies should be implemented equitably across sociodemographic groups.

Program assessment of efforts to improve the quality of postpartum counselling in health centers in Morogoro region, Tanzania.

BACKGROUND: The postpartum period represents a critical window where many maternal and child deaths occur. We assess the quality of postpartum care (PPC) as well as efforts to improve service delivery through additional training and supervision in Health Centers (HCs) in Morogoro Region, Tanzania. METHODS: Program implementers purposively selected nine program HCs for assessment with another nine HCs in the region remaining as comparison sites in a non-randomized program evaluation. PPC quality was assessed by examining structural inputs; provider and client profiles; processes (PNC counselling) and outcomes (patient knowledge) through direct observations of equipment, supplies and infrastructure (n = 18) and PPC counselling (n = 45); client exit interviews (n = 41); a provider survey (n = 62); and in-depth provider interviews (n = 10). RESULTS: While physical infrastructure, equipment and supplies were comparable across study sites (with water and electricity limitations), program areas had better availability of drugs and commodities. Overall, provider availability was also similar across study sites, with 63% of HCs following staffing norms, 17% of Reproductive and Child Health (RCH) providers absent and 14% of those providing PPC being unqualified to do so. In the program area, a median of 4 of 10 RCH providers received training. Despite training and supervisory inputs to program area HCs, provider and client knowledge of PPC was low and the content of PPC counseling provided limited to 3 of 80 PPC messages in over half the consultations observed. Among women attending PPC, 29 (71%) had delivered in a health facility and sought care a median of 13 days after delivery. Barriers to PPC care seeking included perceptions that PPC was of limited benefit to women and was primarily about child health, geographic distance, gaps in the continuity of care, and harsh facility treatment. CONCLUSIONS: Program training and supervision activities had a modest effect on the quality of PPC. To achieve broader transformation in PPC quality, client perceptions about the value of PPC need to be changed; the content of recommended PPC messages reviewed along with the location for PPC services; gaps in the availability of human resources addressed; and increased provider-client contact encouraged.

Program synergies and social relations: implications of integrating HIV testing and counselling into maternal health care on care seeking.

BACKGROUND: Women and children in sub-Saharan Africa bear a disproportionate burden of HIV/AIDS. Integration of HIV with maternal and child services aims to reduce the impact of HIV/AIDS. To assess the potential gains and risks of such integration, this paper considers pregnant women's and providers' perceptions about the effects of integrated HIV testing and counselling on care seeking by pregnant women during antenatal care in Tanzania. METHODS: From a larger evaluation of an integrated maternal and newborn health care program in Morogoro, Tanzania, this analysis included a subset of information from 203 observations of antenatal care and interviews with 57 providers and 190 pregnant women from 18 public health centers in rural and peri-urban settings. Qualitative data were analyzed manually and with Atlas.ti using a framework approach, and quantitative data of respondents' demographic information were analyzed with Stata 12.0. RESULTS: Perceptions of integrating HIV testing with routine antenatal care from women and health providers were generally positive. Respondents felt that integration increased coverage of HIV testing, particularly among difficult-to-reach populations, and improved convenience, efficiency, and confidentiality for women while reducing stigma. Pregnant women believed that early detection of HIV protected their own health and that of their children. Despite these positive views, challenges remained. Providers and women perceived opt out HIV testing and counselling during antenatal services to be compulsory. A sense of powerlessness and anxiety pervaded some women's responses, reflecting the unequal relations, lack of supportive communications and breaches in confidentiality between women and providers. Lastly, stigma surrounding HIV was reported to lead some women to discontinue services or seek care through other access points in the health system. CONCLUSION: While providers and pregnant women view program synergies from integrating HIV services into antenatal care positively, lack of supportive provider-patient relationships, lack of trust resulting from harsh treatment or breaches in confidentiality, and stigma still inhibit women's care seeking. As countries continue rollout of Option B+, social relations between patients and providers must be understood and addressed to ensure that integrated delivery of HIV counselling and services encourages women's care seeking in order to improve maternal and child health.

Supply-side dimensions and dynamics of integrating HIV testing and counselling into routine antenatal care: a facility assessment from Morogoro Region, Tanzania.

BACKGROUND: Integration of HIV into RMNCH (reproductive, maternal, newborn and child health) services is an important process addressing the disproportionate burden of HIV among mothers and children in sub-Saharan Africa. We assess the structural inputs and processes of care that support HIV testing and counselling in routine antenatal care to understand supply-side dynamics critical to scaling up further integration of HIV into RMNCH services prior to recent changes in HIV policy in Tanzania. METHODS: This study, as a part of a maternal and newborn health program evaluation in Morogoro Region, Tanzania, drew from an assessment of health centers with 18 facility checklists, 65 quantitative and 57 qualitative provider interviews, and 203 antenatal care observations. Descriptive analyses were performed with quantitative data using Stata 12.0, and qualitative data were analyzed thematically with data managed by Atlas.ti. RESULTS: Limitations in structural inputs, such as infrastructure, supplies, and staffing, constrain the potential for integration of HIV testing and counselling into routine antenatal care services. While assessment of infrastructure, including waiting areas, appeared adequate, long queues and small rooms made private and confidential HIV testing and counselling difficult for individual women. Unreliable stocks of HIV test kits, essential medicines, and infection prevention equipment also had implications for provider-patient relationships, with reported decreases in women's care seeking at health centers. In addition, low staffing levels were reported to increase workloads and lower motivation for health workers. Despite adequate knowledge of counselling messages, antenatal counselling sessions were brief with incomplete messages conveyed to pregnant women. In addition, coping mechanisms, such as scheduling of clinical activities on different days, limited service availability. CONCLUSION: Antenatal care is a strategic entry point for the delivery of critical tests and counselling messages and the framing of patient-provider relations, which together underpin care seeking for the remaining continuum of care. Supply-side deficiencies in structural inputs and processes of delivering HIV testing and counselling during antenatal care indicate critical shortcomings in the quality of care provided. These must be addressed if integrating HIV testing and counselling into antenatal care is to result in improved maternal and newborn health outcomes.

Predictors of mortality following electrical and lightning injuries in Malawi: A decade of experience.

INTRODUCTION: Electrical injuries can be devastating, and data is lacking in low-resource settings. We aimed to identify predictors of mortality following electrical and lightning injuries (ELI) in Malawi. METHODS: We performed a retrospective observational study of patients presenting with ELI and burn injuries at a tertiary hospital in Malawi from 2011 to 2020. Outcomes were compared and predictors of mortality were modeled. RESULTS: A total of 382 ELI and 6371 burn patients were included. The mean ages for ELI and burn groups were 24 ± 14 and 11 ± 14 years, respectively (p < 0.01). Most patients were injured at home (91% in the burn group versus 51% in the ELI group, p < 0.01). The crude mortality rate in the ELI group was 28%, compared to 12% in the burn group (p < 0.01). On multivariate logistic regression, predictors of mortality included ELI (odds ratio [OR] 13.3, 95% confidence interval [CI] 7.2-24.5) and total body surface area burned (OR 1.1, 95% CI 1.1-1.1). Predicted mortality for ELI has increased over time (p = 0.05). CONCLUSIONS: ELI confers more than 13 times higher odds of mortality than burn injuries in Malawi, with mortality risk increasing over time. More efforts are needed to prevent electrical hazards and implement timely interventions for patients with ELI.

Differential Prognostic Value of Residual Nodal Burden in Breast Cancer Subtypes.

Purpose Residual cancer burden (RCB) index after neoadjuvant chemotherapy (NAC) is highly prognostic in patients with breast cancer (BC) but does not account for subtype or the precise impact of residual nodal burden (RNB). We aimed to precisely define the effect of RNB on survival by subtypes. Methods Adult women with non-metastatic BC diagnosed from 2006-2021 in the National Cancer Database (NCDB) who received NAC followed by surgery within 8 months were included. RNB was also evaluated as a predictor of mortality with multivariable logistic regression. Kaplan-Meier analyses were performed to compare overall survival. Results 51,917 patients were included. After adjustment, ypN stage was the strongest predictor of mortality, with an odds ratio (OR) of 2.24 (95% CI 2.08-2.41) for ypN1 vs ypN0 and increased with increasing nodal burden - ypN2 vs ypN0 OR 5.03, 95% CI 4.60-5.51 and ypN3 vs ypN0 OR 8.85, 95% CI 7.88-9.93. Stratification of survival curves with higher RNB is most pronounced for triple-negative breast cancer (TNBC) with an absolute difference of 64% in 5-year overall survival between ypN0 and ypN3 patients, and lowest for the ER+/HER2- subtype with a 25% absolute difference in 5-year OS between ypN0 and ypN3 patients. On interaction analysis, ypN status was a stronger predictor of mortality for the TNBC subtype compared to other subtypes. Conclusion RNB has a significantly different impact on survival by BC subtypes. Future study of optimal therapeutic strategies for patients with residual nodal disease after NAC should account for subtype specific differences in prognosis.

Predictors of mortality for perforated peptic ulcer disease in Malawi.

BACKGROUND: Mortality from perforated peptic ulcer disease (PUD) remains high, especially in sub-Saharan Africa. We sought to identify predictors of mortality following surgery for perforated PUD. METHODS: We performed a retrospective study of acute care surgeries at Kamuzu Central Hospital (KCH) in Malawi from 2013 to 2022. Patients undergoing omental patch surgeries were included. Bivariate and multivariate analyses were used to model predictors of mortality. RESULTS: A total of 248 patients were included. The mean age was 30 ± 15 years. Ninety percent were male. Mortality rate was 22.2%. Predictors of mortality included age (adjusted odds ratio [AOR] 1.06, 95% confidence interval [CI] 1.03-1.09), shock index (AOR 1.86, 95% CI 1.14-3.03), days to operative intervention (AOR 1.44, 95% CI 1.10-1.88), and presence of complications (AOR 9.65, 95% CI 3.79-24.6). CONCLUSIONS: Mortality following surgery for perforated PUD remains high in this low-resource environment. In-hospital delay is a significant and modifiable predictor of mortality.

Pediatric Traumatic Brain Injury in Malawi: A Propensity-Weighted Analysis of Outcomes and Trends Over Time.

BACKGROUND: Pediatric injuries contribute to substantial mortality and morbidity worldwide, particularly in sub-Saharan Africa. We aim to identify predictors of mortality and time trends for pediatric traumatic brain injuries (TBIs) in Malawi. METHODS: We performed a propensity-matched analysis of data from the trauma registry at Kamuzu Central Hospital in Malawi from 2008 to 2021. All children ≤16 years of age were included. Demographic and clinical data were collected. Outcomes were compared between patients with and without head injuries. RESULTS: A cohort of 54,878 patients was included, with 1755 having TBI. The mean ages of patients with and without TBI were 7.8 ± 7.8 years and 7.1 ± 4.5 years, respectively. The most common mechanism for patients with and without TBI was road traffic injury and falls, respectively (48.2% vs. 47.8%, P < 0.01). The crude mortality rate for the TBI cohort was 20.9% compared to 2.0% in the non-TBI cohort (P < 0.01). After propensity matching, patients with TBI had 4.7 higher odds of mortality (95% confidence interval 1.9-11.8). Over time, patients with TBI had an increasing predicted probability of mortality for all age categories, with the most significant increase among children younger than 1 year. CONCLUSIONS: TBI confers a greater than 4-fold higher likelihood of mortality in this pediatric trauma population in a low-resource setting. These trends have worsened over time.

Pathologic complete response and survival after neoadjuvant chemotherapy in cT1-T2/N0 HER2+ breast cancer.

Women with small HER2+ breast cancers may have excellent prognosis with adjuvant single-agent chemotherapy and HER2-targeted therapy. The role of de-escalated therapy in the neoadjuvant setting, however, remains uncertain. We conducted a cohort study of adult women with T1-2/cN0 HER2+ breast cancer diagnosed 2013-2016 in the National Cancer Database treated with neoadjuvant chemotherapy (NAC) and HER2-targeted therapy. Factors associated with pathologic complete response (pCR) and overall survival were examined. In total, 6994 patients were included, 32% cT1 and 68% cT2. Multi-agent NAC was given to 90% of women while single-agent NAC was given to 10% of women. pCR was achieved in 46% of cT2 patients and 43% of cT1, and in 46% of patients treated with multi-agent versus 38% single agent. Patients receiving multi-agent chemotherapy were younger, had fewer comorbidities, and had higher cT stage and grade. In all patients, pCR was associated with improved survival (p < 0.01). Multi-agent chemotherapy (OR 1.3, p = 0.003), hormone receptor negative (OR 2.6, p < 0.001), higher grade (OR 2.2, p < 0.001), younger age (OR 1.4, p = 0.011), and later year of diagnosis (OR 1.3, p = 0.005) were associated with achieving pCR. Multi-agent chemotherapy was associated with higher likelihood of pCR, but this effect was modest compared to other factors. Single-agent NAC with HER2-directed therapy in selected patients may provide excellent outcome with reduced toxicity, while allowing escalated therapy in the adjuvant setting for patients with residual disease. Prospective studies are needed to determine effects of de-escalation in the neoadjuvant setting on survival and optimal selection strategies.

A Novel Theory-Based Virtual Reality Training to Improve Patient Safety Culture in the Department of Surgery of a Large Academic Medical Center: Protocol for a Mixed Methods Study.

BACKGROUND: Preventable surgical errors of varying degrees of physical, emotional, and financial harm account for a significant number of adverse events. These errors are frequently tied to systemic problems within a health care system, including the absence of necessary policies/procedures, obstructive cultural hierarchy, and communication breakdown between staff. We developed an innovative, theory-based virtual reality (VR) training to promote understanding and sensemaking toward the holistic view of the culture of patient safety and high reliability. OBJECTIVE: We aim to assess the effect of VR training on health care workers' (HCWs') understanding of contributing factors to patient safety events, sensemaking of patient safety culture, and high reliability organization principles in the laboratory environment. Further, we aim to assess the effect of VR training on patient safety culture, TeamSTEPPS behavior scores, and reporting of patient safety events in the surgery department of an academic medical center in the clinical environment. METHODS: This mixed methods study uses a pre-VR versus post-VR training study design involving attending faculty, residents, nurses, technicians of the department of surgery, and frontline HCWs in the operation rooms at an academic medical center. HCWs' understanding of contributing factors to patient safety events will be assessed using a scale based on the Human Factors Analysis and Classification System. We will use the data frame theory framework, supported by a semistructured interview guide to capture the sensemaking process of patient safety culture and principles of high reliability organizations. Changes in the culture of patient safety will be quantified using the Agency for Healthcare Research and Quality surveys on patient safety culture. TeamSTEPPS behavior scores based on observation will be measured using the Teamwork Evaluation of Non-Technical Skills tool. Patient safety events reported in the voluntary institutional reporting system will be compared before the training versus those after the training. We will compare the Agency for Healthcare Research and Quality patient safety culture scores and patient safety events reporting before the training versus those after the training by using descriptive statistics and a within-subject 2-tailed, 2-sample t test with the significance level set at .05. RESULTS: Ethics approval was obtained in May 2021 from the institutional review board of the University of North Carolina at Chapel Hill (22-1150). The enrollment of participants for this study will start in fall 2022 and is expected to be completed by early spring 2023. The data analysis is expected to be completed by July 2023. CONCLUSIONS: Our findings will help assess the effectiveness of VR training in improving HCWs' understanding of contributing factors of patient safety events, sensemaking of patient safety culture, and principles and behaviors of high reliability organizations. These findings will contribute to developing VR training to improve patient safety culture in other specialties.