Assessment of Distinct Gut Microbiome Signatures in a Diverse Cohort of Patients Undergoing Definitive Treatment for Rectal Cancer.

Introduction: Disparities in incidence and outcome of rectal cancer are multifactorial in etiology but may be due, in part, to differences in gut microbiome composition. We used serial robust statistical approaches to assess baseline gut microbiome composition in a diverse cohort of patients with rectal cancer receiving definitive treatment. Methods: Microbiome composition was compared by age at diagnosis (< 50 vs ≥ 50 years), race and ethnicity (White Hispanic vs non-Hispanic), and response to therapy. Alpha diversity was assessed using the Shannon, Chao1, and Simpson diversity measures. Beta diversity was explored using both Bray-Curtis dissimilarity and Aitchison distance with principal coordinate analysis. To minimize false-positive findings, we used two distinct methods for differential abundance testing: LinDA and MaAsLin2 (all statistics two-sided, Benjamini-Hochberg corrected false discovery rate < 0.05). Results: Among 64 patients (47% White Hispanic) with median age 51 years, beta diversity metrics showed significant clustering by race and ethnicity (p < 0.001 by both metrics) and by onset (Aitchison p = 0.022, Bray-Curtis p = 0.035). White Hispanic patients had enrichment of bacterial family Prevotellaceae (LinDA fold change 5.32, MaAsLin2 fold change 5.11, combined adjusted p = 0.0007). No significant differences in microbiome composition were associated with neoadjuvant therapy response. Conclusion: We identified distinct gut microbiome signatures associated with race and ethnicity and age of onset in a diverse cohort of patients undergoing definitive treatment for rectal cancer.

Large Language Model Prompting Techniques for Advancement in Clinical Medicine.

Large Language Models (LLMs have the potential to revolutionize clinical medicine by enhancing healthcare access, diagnosis, surgical planning, and education. However, their utilization requires careful, prompt engineering to mitigate challenges like hallucinations and biases. Proper utilization of LLMs involves understanding foundational concepts such as tokenization, embeddings, and attention mechanisms, alongside strategic prompting techniques to ensure accurate outputs. For innovative healthcare solutions, it is essential to maintain ongoing collaboration between AI technology and medical professionals. Ethical considerations, including data security and bias mitigation, are critical to their application. By leveraging LLMs as supplementary resources in research and education, we can enhance learning and support knowledge-based inquiries, ultimately advancing the quality and accessibility of medical care. Continued research and development are necessary to fully realize the potential of LLMs in transforming healthcare.

An IL-17-DUOX2 axis controls gastrointestinal colonization by Candida albicans.

Candida albicans is a ubiquitous fungus in the human gut microbiome as well as a prevalent cause of opportunistic mucosal and systemic disease. There is currently little understanding, however, as to how crosstalk between C. albicans and the host regulates colonization of this key niche. Here, we performed expression profiling on ileal and colonic tissues in germ-free mice colonized with C. albicans to define the global response to this fungus. We reveal that Duox2 and Duoxa2 , encoding dual NADPH oxidase activity, are upregulated in both the ileum and colon, and that induction requires the C. albicans yeast-hyphal transition and the hyphal-specific toxin candidalysin. Hosts lacking the IL-17 receptor failed to upregulate Duox2/Duoxa2 in response to C. albicans , while addition of IL-17A to colonoids induced these genes together with the concomitant production of hydrogen peroxide. To directly define the role of Duox2/Duoxa2 in fungal colonization, antibiotic-treated mice lacking intestinal DUOX2 activity were evaluated for C. albicans colonization and host responses. Surprisingly, loss of DUOX2 function reduced fungal colonization at extended time points (>17 days colonization) and increased the proportion of hyphal cells in the gut. IL-17A levels were also elevated in C. albicans -colonized mice lacking functional DUOX2 highlighting cross-regulation between this cytokine and DUOX2. Together, these experiments reveal novel links between fungal cells, candidalysin toxin and the host IL-17-DUOX2 axis, and that a complex interplay between these factors regulates C. albicans filamentation and colonization in the gut.

Catheter Ablation versus Advanced Therapy for Patients with Severe Heart Failure and Ventricular Electrical Storm.

BACKGROUND: Current data on outcomes of an initial strategy of catheter ablation versus advanced therapy in patients with severe HF and ES are limited. OBJECTIVE: To evaluate the outcomes of ventricular tachycardia (VT) ablation versus left ventricular assist device (LVAD) or heart transplantation (HT) in patients with severe heart failure (HF) and ventricular electric storm (ES). METHODS: Patients with severe HF and ES who underwent VT ablation, LVAD, or HT between 2012 and 2022 at our medical center were reviewed. Severe HF was defined as ejection fraction ≤ 35% or presence of severe restrictive, valvular or genetic cardiomyopathy. We assessed in-hospital adverse events and one-year outcomes between the two groups. RESULTS: Of 73 patients, 43 underwent VT ablation and 30 received advanced therapy (21 HT and 9 LVAD). One-year survival was similar (76.7% vs 86.7%, log-rank p = 0.308). However, 10 patients (23.3%) in the ablation group underwent HT during follow up. After multivariable analysis, UNOS status 1 or 2 by VT criteria (HR 5.52, 95% CI: 1.27-24.12; p = 0.023) and early VT recurrence (HR 5.67, 95% CI: 1.68-19.09; p = 0.005) were associated with HT or mortality in patients who underwent VT ablation. CONCLUSION: Patients with severe HF and ES who underwent VT ablation had similar overall survival as patients who directly proceeded with advanced therapy, although rates of HT were high during follow up. Predictors of HT or mortality after catheter ablation include UNOS status 1 or 2 by VT criteria and early VT recurrence.

Sex-based difference in immune responses and efficacy of the pneumococcal conjugate vaccine.

Vaccine-mediated protection and susceptibility to Streptococcus pneumoniae (pneumococcus) infections are influenced by biological sex. The incidence of invasive pneumococcal disease remains higher in males compared to females even after the introduction of the pneumococcal conjugate vaccine (PCV). However, sex-based differences in the immune response to this conjugate vaccine remain unexplored. To investigate those differences, we vaccinated adult male and female mice with PCV and assessed cellular and humoral immune responses. Compared to females, male mice displayed lower levels of T follicular helper cells, germinal center B cells and plasmablasts, which are all required for antibody production following vaccination. This was linked to lower IgG and IgM levels against pneumococci and lower isotype switching to IgG3 in vaccinated males. Due to lower antibody levels, sera of vaccinated male mice had lower efficacy in several anti-pneumococcal functions including neutralization of bacterial binding to pulmonary epithelial cells as well as direct cytotoxicity against S. pneumoniae. Importantly, while the vaccine was highly protective in females, vaccinated males succumbed to infection more readily and were more susceptible to both lung-localized infection and systemic spread following S. pneumoniae challenge. These findings identify sex-based differences in immune responses to PCV that can inform future vaccine strategies.

Technical Factors Associated With the Benefit of Prophylactic Pancreatic Stent Placement During High-Risk Endoscopic Retrograde Cholangiopancreatography: A Secondary Analysis of the SVI Trial Data Set.

INTRODUCTION: Prophylactic pancreatic stent placement (PSP) is effective for preventing pancreatitis after endoscopic retrograde cholangiopancreatography (ERCP) in high-risk cases, but the optimal technical approach to this intervention remains uncertain. METHODS: In this secondary analysis of 787 clinical trial patients who underwent successful stent placement, we studied the impact of (i) whether pancreatic wire access was achieved for the sole purpose of PSP or naturally during the conduct of the case, (ii) the amount of effort expended on PSP, (iii) stent length, (iv) stent diameter, and (v) guidewire caliber. We used logistic regression models to examine the adjusted association between each technical factor and post-ERCP pancreatitis (PEP). RESULTS: Ninety-one of the 787 patients experienced PEP. There was no clear association between PEP and whether pancreatic wire access was achieved for the sole purpose of PSP (vs occurring naturally; odds ratio [OR] 0.82, 95% confidence interval [CI] 0.37-1.84), whether substantial effort expended on stent placement (vs nonsubstantial effort; OR 1.58, 95% CI 0.73-3.45), stent length (>5 vs ≤5 cm; OR 1.01, 95% CI 0.63-1.61), stent diameter (≥5 vs <5 Fr; OR 1.13, 95% CI 0.65-1.96), or guidewire caliber (0.035 vs 0.025 in; 0.83, 95% CI 0.49-1.41). DISCUSSION: The 5 modifiable technical factors studied in this secondary analysis of large-scale randomized trial data did not appear to have a strong impact on the benefit of prophylactic PSP in preventing PEP after high-risk ERCP. Within the limitations of post hoc subgroup analysis, these findings may have important implications in procedural decision making and suggest that the benefit of PSP is robust to variations in technical approach.

North American Expert Consensus on the Post-procedural Care of Patients After Per-oral Endoscopic Myotomy Using a Delphi Process.

BACKGROUND & AIMS: There is significant variability in the immediate post-operative and long-term management of patients undergoing per-oral endoscopic myotomy (POEM), largely stemming from the lack of high-quality evidence. We aimed to establish a consensus on several important questions on the after care of post-POEM patients through a modified Delphi process. METHODS: A steering committee developed an initial questionnaire consisting of 5 domains (33 statements): post-POEM admission/discharge, indication for immediate post-POEM esophagram, peri-procedural medications and diet resumption, clinic follow-up recommendations, and post-POEM reflux surveillance and management. A total of 34 experts participated in the 2 rounds of the Delphi process, with quantitative and qualitative data analyzed for each round to achieve consensus. RESULTS: A total of 23 statements achieved a high degree of consensus. Overall, the expert panel agreed on the following: (1) same-day discharge after POEM can be considered in select patients; (2) a single dose of prophylactic antibiotics may be as effective as a short course; (3) a modified diet can be advanced as tolerated; and (4) all patients should be followed in clinic and undergo objective testing for surveillance and management of reflux. Consensus could not be achieved on the indication of post-POEM esophagram to evaluate for leak. CONCLUSIONS: The results of this Delphi process established expert agreement on several important issues and provides practical guidance on key aspects in the care of patients following POEM.

Deep learning for detecting and characterizing oil and gas well pads in satellite imagery.

Methane emissions from the oil and gas sector are a large contributor to climate change. Robust emission quantification and source attribution are needed for mitigating methane emissions, requiring a transparent, comprehensive, and accurate geospatial database of oil and gas infrastructure. Realizing such a database is hindered by data gaps nationally and globally. To fill these gaps, we present a deep learning approach on freely available, high-resolution satellite imagery for automatically mapping well pads and storage tanks. We validate the results in the Permian and Denver-Julesburg basins, two high-producing basins in the United States. Our approach achieves high performance on expert-curated datasets of well pads (Precision = 0.955, Recall = 0.904) and storage tanks (Precision = 0.962, Recall = 0.968). When deployed across the entire basins, the approach captures a majority of well pads in existing datasets (79.5%) and detects a substantial number (>70,000) of well pads not present in those datasets. Furthermore, we detect storage tanks (>169,000) on well pads, which were not mapped in existing datasets. We identify remaining challenges with the approach, which, when solved, should enable a globally scalable and public framework for mapping well pads, storage tanks, and other oil and gas infrastructure.

Controlled interlayer exciton ionization in an electrostatic trap in atomically thin heterostructures.

Atomically thin semiconductor heterostructures provide a two-dimensional (2D) device platform for creating high densities of cold, controllable excitons. Interlayer excitons (IEs), bound electrons and holes localized to separate 2D quantum well layers, have permanent out-of-plane dipole moments and long lifetimes, allowing their spatial distribution to be tuned on demand. Here, we employ electrostatic gates to trap IEs and control their density. By electrically modulating the IE Stark shift, electron-hole pair concentrations above 2 × 1012 cm-2 can be achieved. At this high IE density, we observe an exponentially increasing linewidth broadening indicative of an IE ionization transition, independent of the trap depth. This runaway threshold remains constant at low temperatures, but increases above 20 K, consistent with the quantum dissociation of a degenerate IE gas. Our demonstration of the IE ionization in a tunable electrostatic trap represents an important step towards the realization of dipolar exciton condensates in solid-state optoelectronic devices.

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Impact on Quality of Life (QoL) of Persons with ME/CFS.

Background and Objectives: We previously reported on the impact of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) on the QoL of persons with ME/CFS and their family members. Here, we present the findings of the impact on the QoL of individuals with ME/CFS whose family members did not participate in the survey. Materials and Methods: A prospective multinational online survey was disseminated via patient charities, support groups and social media. Persons with ME/CFS completed the EuroQoL questionnaire (EQ-5D-3L). Results: Data were analysed from 876 participants from 26 countries who reported a health care professional diagnosis of ME/CFS. In total, 742 participants identified as female, 124 male and 10 preferred not to say. The mean age of the participants was 47 years (range 18-82), and the mean time to diagnosis was 14 years. The mean overall health status on a visual analogue scale for people with ME/CFS was 36.4 (100 = best health). People with ME/CFS were most often affected by inability to perform usual activities (n = 852, 97%), followed by pain (n = 809, 92%), impaired mobility (n = 724, 83%), difficulty in self-care (n = 561, 64%) and least often affected by anxiety and depression (n = 540, 62%). Conclusions: The QoL of people with ME/CFS is significantly affected globally. There was no significant difference in quality of life compared with previously published data on those with ME/CFS who did have a family member complete the family member quality of life questionnaire (FROM16). Contrary to popular misconception, anxiety and depression are the least often affected areas in persons with ME/CFS who are most impacted by their inability to perform usual activities.

Outcomes of cooled radiofrequency ablation of cervical nerves for the treatment of chronic pain.

BACKGROUND: Chronic pain, defined as pain persisting for more than 3-6 months, has a mean one-year prevalence in the United States of 25.8% and is one of the most frequent reasons adults seek medical care. Treatment options include physical therapy, analgesics, anticonvulsants, exercise, and muscle relaxants. Even with conventional treatment modalities, in a subset of patients, pain may persist. Cooled radiofrequency ablation (c-RFA), a minimally invasive therapy, employs thermal energy generated by electrical currents to disrupt the transmission of pain stimuli along nociceptive pathways. This leads to an attenuation of pain impulses, primarily through nerve tissue necrosis. The potential of c-RFA to alleviate chronic pain for patients who struggle to find relief elsewhere accentuates the importance of rigorously investigating its outcomes. This study investigates whether patients receiving c-RFA for relief of chronic neck pain caused by cervical facet joint arthropathy experience a reduction in pain scores, the length of this reduction in pain scores, and the magnitude of this reduction in pain. METHODS: This study was a retrospective analysis of data extracted from UW-Health Electronic Medical Health records (EMR), encompassing cervical c-RFA procedures performed from 2015 through 2022. Patient data were obtained, including diagnosis, pre-operative pain score, post-operative pain score, duration of relief, patient age, sex, and BMI. A two-tailed paired t-test was used to statistically analyze the pre-operative and post-operative pain scores, in which a p-value ≤0.05 was considered significant. RESULTS: A total of 450 cervical c-RFA procedures were reviewed, 152 were excluded due to absent pre- or post-op pain scores. 298 were included in the analysis, comprising 203 unique patients: 129 females and 74 males with an average age of 56.03 ± 12.76 and a BMI of 28.76 ± 6.05. Improvement of pain symptoms was reported in 85.23% (n = 263), 6% (n = 19) reported complete pain remission, 8.72% (n = 26) reported no change, and 3.02% (n = 9) reported worsening symptoms. Patients reported an average pre-operative pain score of 6.15 (M = 6.15, SD = 1.55) and an average post-operative pain score of 3.64 (M = 3.64, SD = 2.09) this achieved significance (p < 0.0001). Of the 85.23% (n = 263) charts that noted improvement, there is an average of 48.04% ± 26.53 reduction from their pre-operative pain scores. The average duration of relief lasted 6.67 ± 4.84 months. CONCLUSION: This study supports the potential efficacy of c-RFA as a minimally invasive treatment for chronic neck pain secondary to cervical facet joint arthropathy refractory to conventional treatment measures, demonstrating significant relief for a substantial length of time. Due to chronic pain's detrimental effect on one's quality of life, finding effective treatment options is essential, especially for those refractory to conventional treatments.

Breathe and bloom: Gut hypoxia limits C. albicans growth.

Multiple host and microbial factors dictate whether Candida albicans can colonize the mammalian gastrointestinal tract. In this issue of Cell Host & Microbe, Savage et al. demonstrate that restoration of intestinal epithelial hypoxia is sufficient to restore Candida albicans colonization resistance, even when other Candida inhibitory effectors remain depleted.

Frequency and preventability of adverse drug events in the outpatient setting.

BACKGROUND: Limited data exist regarding adverse drug events (ADEs) in the outpatient setting. The objective of this study was to determine the incidence, severity, and preventability of ADEs in the outpatient setting and identify potential prevention strategies. METHODS: We conducted an analysis of ADEs identified in a retrospective electronic health records review of outpatient encounters in 2018 at 13 outpatient sites in Massachusetts that included 13 416 outpatient encounters in 3323 patients. Triggers were identified in the medical record including medications, consultations, laboratory results, and others. If a trigger was detected, a further in-depth review was conducted by nurses and adjudicated by physicians to examine the relevant information in the medical record. Patients were included in the study if they were at least 18 years of age with at least one outpatient encounter with a physician, nurse practitioner or physician's assistant in that calendar year. Patients were excluded from the study if the outpatient encounter occurred in outpatient surgery, psychiatry, rehabilitation, and paediatrics. RESULTS: In all, 5% of patients experienced an ADE over the 1-year period. We identified 198 ADEs among 170 patients, who had a mean age of 60. Most patients experienced one ADE (87%), 10% experienced two ADEs and 3% experienced three or more ADEs. The most frequent drug classes resulting in ADEs were cardiovascular (25%), central nervous system (14%), and anti-infective agents (14%). Severity was ranked as significant in 85%, 14% were serious, 1% were life-threatening, and there were no fatal ADEs. Of the ADEs, 22% were classified as preventable and 78% were not preventable. We identified 246 potential prevention strategies, and 23% of ADEs had more than one prevention strategy possibility. CONCLUSIONS: Despite efforts to prioritise patient safety, medication-related harms are still frequent. These results underscore the need for further patient safety improvement in the outpatient setting.

A Calculated Risk: Evaluation of QTc Drug-Drug Interaction (DDI) Clinical Decision Support (CDS) Alerts and Performance of the Tisdale Risk Score Calculator.

INTRODUCTION: A risk factor for a potentially fatal ventricular arrhythmia Torsade de Pointes is a prolongation in the heart rate-corrected QT interval (QTc) ≥ 500 milliseconds (ms) or an increase of ≥ 60 ms from a patient's baseline value, which can cause sudden cardiac death. The Tisdale risk score calculator uses clinical variables to predict which hospitalized patients are at the highest risk for QTc prolongation. OBJECTIVE: To determine the rate of overridden QTc drug-drug interaction (DDI)-related clinical decision support (CDS) alerts per patient admission and the prevalence by Tisdale risk score category of these overridden alerts. Secondary outcome was to determine the rate of drug-induced QTc prolongation (diQTP) associated with overrides. METHODS: Our organization's enterprise data warehouse was used to retrospectively access QTc DDI alerts presented for patients aged ≥ 18 years who were admitted to Brigham and Women's Hospital during 2022. The QTc DDI CDS alerts were included if shown to a physician, fellow, resident, physician assistant, or nurse practitioner when entering the order in inpatient areas for patients with a length of stay of at least 2 days. Variables collected for the Tisdale calculator included age, sex, whether patient was on a loop diuretic, potassium level, admission QTc value, admitting diagnosis of acute myocardial infarction, sepsis, or heart failure, and number of QTc-prolonging drugs given to the patient. RESULTS: A total of 2649 patients with 3033 patient admissions had 18,432 QTc DDI alerts presented that were overridden. An average of 3 unique QTc DDI alerts were presented per patient admission and the alerts were overridden an average of 6 times per patient admission. Overall, 6% of patient admissions were low risk (score ≤ 6), 64% moderate risk (score 7-10), and 30% high risk (score ≥ 11) of QTc prolongation. The most common QTc DDI alerts overridden resulting in an diQTP were quetiapine and propofol (11%) and amiodarone and haloperidol (7%). The diQTP occurred in 883 of patient admissions (29%) and was more frequent in those with higher risk score, with 46% of patient admissions with diQTP in high risk, 23% in moderate risk, and 8% in low risk. CONCLUSION: Use of the Tisdale calculator to assess patient-specific risk of QT prolongation combined with CDS may improve overall alert quality and acceptance rate, which may decrease the diQTP rate.

Early safety of endoscopic sleeve gastroplasty in super obesity (body mass index > 50).

BACKGROUND: The prevalence of super obesity (body mass index [BMI] > 50) continues to rise. However, the adoption of bariatric surgery in this population remains very low. There are limited studies evaluating the utility of endoscopic sleeve gastroplasty (ESG) in super obesity. OBJECTIVES: The purpose of this study is to evaluate the short-term safety profile of ESG in patients with super obesity using data from the Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program database. SETTING: United States. METHODS: We retrospectively analyzed patients who underwent ESG and sleeve gastrectomy (SG) from 2016 to 2021. Patients with BMI >50 who underwent ESG were compared to ESG patients with BMI <50 and also SG patients with BMI >50. Primary outcomes included the incidence of severe adverse events (AEs), hospital readmission, reintervention, and reoperation within 30 days of the primary procedure. Secondary outcomes included procedure time, hospital length of stay, and total body weight loss at 30 days. RESULTS: There were no significant differences in AE, reoperations, hospital readmissions, or reinterventions for patients with super obesity undergoing ESG, compared to patients with BMI below 50. Mean total body weight loss was greater in patients with super obesity. There were no significant differences in AEs for patients with super obesity who underwent ESG versus SG, although ESG patients had more hospital readmissions, reinterventions, and reoperations. CONCLUSIONS: ESG may be performed safely, with comparable safety to SG, in patients with BMI as high as 70. However, further studies are needed to validate the feasibility and long-term efficacy prior to clinical implementation.

Survival benefit associated with screening of patients at elevated risk for pancreatic cancer.

BACKGROUND & OBJECTIVES: Screening for pancreatic cancer is recommended for individuals with a strong family history, certain genetic syndromes, or a neoplastic cyst of the pancreas. However, limited data supports a survival benefit attributable to screening these higher-risk individuals. METHODS: All patients enrolled in screening at a High-Risk Pancreatic Cancer Clinic (HRC) from July 2013 to June 2020 were identified from a prospectively maintained institutional database and compared to patients evaluated at a Surgical Oncology Clinic (SOC) at the same institution during the same period. Clinical outcomes of patients selected for surgical resection, particularly clinicopathologic stage and overall survival, were compared. RESULTS: Among 826 HRC patients followed for a median (IQR) of 2.3 (0.8-4.2) years, 128 were selected for surgical resection and compared to 402 SOC patients selected for resection. Overall survival was significantly longer among HRC patients (median survival: not reached vs. 2.6 years, p < 0.001). Among 31 HRC and 217 SOC patients with a diagnosis of pancreatic ductal adenocarcinoma (PDAC), the majority of HRC patients were diagnosed with stage 0 disease (carcinoma in situ), while the majority of SOC patients were diagnosed with stage II disease (p < 0.001). Overall survival after resection of invasive PDAC was also significantly longer among HRC patients compared to SOC patients (median survival 5.5 vs. 1.6 years, p = 0.002). CONCLUSION: Patients at increased risk for PDAC and followed with guideline-based screening exhibited downstaging of disease and improved survival from PDAC in comparison to patients who were not screened.

Preintervention Wait Time and Survival in People With Rheumatic Heart Disease in Uganda.

BACKGROUND: There is an unmet surgical burden among people living with rheumatic heart disease (RHD) in Uganda. Nevertheless, risk factors associated with time to first intervention and preoperative mortality are poorly understood. METHODS: Individuals with RHD who met indications for valve surgery were identified using the Uganda National RHD Registry (January 2010-August 2022). Kaplan-Meier estimates and multivariable Cox proportional hazard models were used. RESULTS: Of the cohort with clinical RHD, 64% (1452 of 2269) met criteria for an index operation. Of those, 13.5% obtained a surgical intervention, whereas 30.6% died before the operation. The estimated likelihood of first operation was 50% at 9.3 years of follow-up (95% CI, 8.1-upper limit not reached). Intervention was more likely in men vs women (hazard ratio [HR], 1.78; 95% CI, 1.21-2.64), those with postsecondary education vs primary school or less (HR, 3.60; 95% CI, 1.88-6.89), and those with a history of atrial fibrillation (HR, 2.78; 95% CI, 1.63-4.76). Surgical intervention was less likely for adults vs those aged <18 years (HR, 0.49; 95% CI, 0.32-0.77) and those with New York Heart Association Functional Class III/IV vs I/II (HR, 0.51; 95% CI, 0.32-0.83). The median preoperative survival time among those awaiting first operation was 4.6 years (95% CI, 3.9-5.7 years). History of infective endocarditis, right ventricular dysfunction, pericardial effusion, atrial fibrillation, and having surgical indications for multiple valves were associated with increased probability of death. CONCLUSIONS: Our analysis revealed a prolonged time to first surgical intervention and high preintervention death for RHD in Uganda, with factors such as age, sex, and education level remaining barriers to obtaining surgery.