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Oxalate, a uremic toxin that accumulates in dialysis patients, is associated with cardiovascular disease. As oxalate crystals can activate immune cells, we tested the hypothesis that plasma oxalate would be associated with cytokine concentrations and cardiovascular outcomes in dialysis patients. In a cohort of 104 US patients with kidney failure requiring dialysis (cohort 1), we measured 21 inflammatory markers. As IL-16 was the only cytokine to correlate with oxalate, we focused further investigations on IL-16. We searched for associations between concentrations of IL-16 and mortality and cardiovascular events in the 4D cohort (1255 patients, cohort 2) and assessed further associations of IL-16 with other uremic toxins in this cohort. IL-16 levels were positively correlated with pOx concentrations (ρ = 0.39 in cohort 1, r = 0.35 in cohort 2) and were elevated in dialysis patients when compared to healthy individuals. No significant association could be found between IL-16 levels and cardiovascular events or mortality in the 4D cohort. We conclude that the cytokine IL-16 correlates with plasma oxalate concentrations and is substantially increased in patients with kidney failure on dialysis. However, no association could be detected between IL-16 concentrations and cardiovascular disease in the 4D cohort., (© 2024. The Author(s).)

Background: Palliative treatment has been associated with improved quality of life and survival for a wide variety of metastatic cancers. However, it is unclear whether the benefits of palliative treatment are uniformly experienced across the US cancer population. We evaluated patterns and outcomes of palliative treatment based on socioeconomic, sociodemographic and treating facility characteristics., Methods: Patients diagnosed between 2008 and 2019 with Stage IV primary cancer of nine organ sites were analyzed in the National Cancer Database. The association between identified variables, and outcomes concerning the administration of palliative treatment were analyzed with multivariable logistic regression and Cox proportional hazard models., Results: Overall 238,995 (23.6%) of Stage IV patients received palliative treatment, which increased over time for all cancers (from 20.7% in 2008 to 25.6% in 2019). Palliative treatment utilization differed significantly by region (West less than Northeast, OR: 0.55 [0.54-0.56], p < 0.001) and insurance payer status (uninsured greater than private insurance, OR: 1.35 [1.32-1.39], p < 0.001). Black race and Hispanic ethnicity were also associated with lower rates of palliative treatment compared to White and non-Hispanics respectively (OR for Blacks: 0.91 [0.90-0.93], p < 0.001 and OR for Hispanics: 0.79 [0.77-0.81] p < 0.001)., Conclusions: There are important differences in the utilization of palliative treatment across different populations in the United States. A better understanding of variability in palliative treatment use and outcomes may identify opportunities to improve informed decision making and optimize quality of care at the end-of-life., (© 2024 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Background: In some cases of right-sided lung cancer, tumor extension, bronchial involvement, or pulmonary artery infiltration may necessitate bilobectomy. Although the middle lobe is believed to represent a fraction of total lung function, the morbidity and mortality associated with bilobectomy is not well described., Methods: We retrospectively identified patients in The Society of Thoracic Surgeons Database who underwent lobectomy, bilobectomy, or pneumonectomy for lung cancer from 2009 to 2017. The primary outcome was 30-day perioperative mortality. We performed propensity matching by patient demographics, comorbidities, and perioperative variables for each surgical type against bilobectomy and ran Cox proportional hazard models. Secondary outcomes of 30-day morbidity and mortality of upper vs lower bilobectomy were also compared., Results: Within the study period 2911 bilobectomy, 65,506 lobectomy, and 3370 pneumonectomy patients met the inclusion criteria. Patients undergoing pneumonectomy and bilobectomy had fewer comorbidities than lobectomy patients. After propensity matching 30-day mortality of bilobectomy was comparable with left pneumonectomy (hazard ratio [HR], 1.35; 95% CI, 0.95-1.91; P = .09) and significantly worse than left (HR, 0.40; 95% CI, 0.29-0.56; P < .0001) or right (HR, 0.43; 95% CI, 0.31-0.59; P < .0001) lobectomy. Bilobectomy was associated with a survival advantage compared with right pneumonectomy (HR, 2.54; 95% CI, 1.72-3.74; P < .0001). Thirty-day morbidity was higher for bilobectomy compared with lobectomy, and upper bilobectomy had a significant unadjusted 30-day mortality advantage compared with lower bilobectomy (98.3% vs 97%, P = .04)., Conclusions: The morbidity and mortality of bilobectomy is significantly worse than lobectomy and is comparable with left pneumonectomy. The addition of middle lobectomy to a pulmonary resection is not without risk and should be carefully considered during preoperative risk stratification., (Copyright © 2024 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Patients with esophageal cancer often receive care in a collaborative (multi-institutional) treatment model as opposed to a single institutional model. The effect of a collaborative model on the quality of trimodality therapy and survival is unknown., Methods: The National Cancer Database (NCDB) was used to identify patients receiving neoadjuvant chemoradiotherapy (CRT) followed by esophagectomy for esophageal cancer between 2012-2017. Patients who received neoadjuvant therapy and surgery at a single institution were compared to those that received collaborative treatment across multiple institutions. Outcomes included adherence to guideline recommended multiagent chemotherapy, receipt of 41.4-50.4 Gy of radiation, R0 resection, pathologic complete response (pCR), and 5-year survival. Sociodemographics, comorbidities, and tumor characteristics were assessed in bivariate and multivariable analysis., Results: Among 8,396 patients identified, 39% received treatment at a single institution, while 61% received collaborative treatment. Median travel distance to the site of esophagectomy was two times greater for patients receiving collaborative treatment (30 vs. 15 miles; P<0.001). Patients in the collaborative cohort were less likely to receive guideline-recommended multiagent chemotherapy (85% vs. 96%; P<0.001) and 41.4-50.4 Gy of radiation (89% vs. 91%; P=0.01). R0 resection rates were similar (94.4% vs. 93.7%; P=0.17). Patients who received collaborative treatment had an increased rate of pCR (24% vs. 22%; P=0.02). Overall, 90-day and 5-year survival were 92.9% and 42.6% respectively and did not differ significantly between the two groups., Conclusions: Collaborative trimodality treatment of esophageal cancer is a common and reasonable practice model, which may alleviate patient travel burden with only a modest impact on the quality of CRT, pCR, 90-day survival, and 5-year survival., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-23-346/coif). DJB was paid a stipend from Iovance to attend a panel discussion on cell-based therapy that was unrelated to this work. The other authors have no conflicts of interest to declare., (2023 Journal of Thoracic Disease. All rights reserved.)

Purpose: This study aims to clarify the association between metastatic pattern and prognosis in stage IV gastric cancer, with a focus on patients presenting with metastases limited to nonregional lymph nodes., Methods: In this retrospective cohort study, the National Cancer Database was used to identify patients ≥ 18 years of age diagnosed with stage IV gastric cancer between 2016 and 2019. Patients were stratified according to pattern of metastatic disease at diagnosis: nonregional lymph nodes only ("stage IV-nodal"), single systemic organ ("stage IV-single organ"), or multiple organs ("stage IV-multi-organ"). Survival was assessed by Kaplan-Meier curves and multivariable Cox models in unadjusted and propensity score-matched samples., Results: Overall, 15,050 patients were identified, including 1,349 (8.7%) stage IV-nodal patients. Most patients in each group received chemotherapy [68.6% of stage IV-nodal patients, 65.2% of stage IV-single organ patients, and 63.5% of stage IV-multi-organ patients (p = 0.003)]. Stage IV-nodal patients exhibited better median survival (10.5 months, 95% CI 9.7-11.9, p < 0.001) than single organ (8.0, 95% CI 7.6-8.2) and multi-organ (5.7, 95% CI 5.4-6.0) patients. In the multivariable Cox model, stage IV-nodal patients also exhibited better survival (HR 0.79, 95% CI 0.73-0.85, p < 0.001) than single organ (reference) and multi-organ (HR 1.27, 95% CI 1.22-1.33, p < 0.001) patients., Conclusions: Nearly 9% of clinical stage IV gastric cancer patients have their distant disease confined to nonregional lymph nodes. These patients were managed similarly to other stage IV patients but experienced a better prognosis, suggesting opportunities to introduce M1 staging subclassifications., (© 2023. Society of Surgical Oncology.)

Oxalate homeostasis is maintained through a delicate balance between endogenous sources, exogenous supply and excretion from the body. Novel studies have shed light on the essential roles of metabolic pathways, the microbiome, epithelial oxalate transporters, and adequate oxalate excretion to maintain oxalate homeostasis. In patients with primary or secondary hyperoxaluria, nephrolithiasis, acute or chronic oxalate nephropathy, or chronic kidney disease irrespective of aetiology, one or more of these elements are disrupted. The consequent impairment in oxalate homeostasis can trigger localized and systemic inflammation, progressive kidney disease and cardiovascular complications, including sudden cardiac death. Although kidney replacement therapy is the standard method for controlling elevated plasma oxalate concentrations in patients with kidney failure requiring dialysis, more research is needed to define effective elimination strategies at earlier stages of kidney disease. Beyond well-known interventions (such as dietary modifications), novel therapeutics (such as small interfering RNA gene silencers, recombinant oxalate-degrading enzymes and oxalate-degrading bacterial strains) hold promise to improve the outlook of patients with oxalate-related diseases. In addition, experimental evidence suggests that anti-inflammatory medications might represent another approach to mitigating or resolving oxalate-induced conditions., (© 2022. Springer Nature Limited.)

Introduction: For patients with stage IV esophageal cancer, esophageal radiation may be used selectively for local control and palliation. We aimed to understand patterns of radiation administration among patients with stage IV esophageal cancer and any potential survival associations., Methods: In this retrospective cohort study, the National Cancer Database was queried for patients with metastatic stage IV esophageal cancer diagnosed between 2016 and 2019. Patterns of radiation use were identified. Survival was determined through Kaplan-Meier analysis of propensity score-matched pairs of patients who did and did not receive radiotherapy and time-to-event models., Results: Overall, 12,088 patients with stage IV esophageal cancer were identified, including 32.7% who received esophageal radiation. The median age was 65 (interquartile range [IQR]: 58-73) years, and 82.6% were male. Among the irradiated patients, the median total radiation dose was 35 (IQR: 30-50) Gy administered in a median of 14 (IQR: 10-25) fractions given in 22 (IQR: 14-39) days. Overall, esophageal radiation was not associated with better survival (log-rank p  = 0.41). When stratified by radiation dose, a survival advantage (over no radiation) was found in the 1144 patients (29% of the irradiated patients) who received 45 to 59.9 Gy (time ratio = 1.28, 95% confidence interval: 1.20-1.37, p < 0.001) and the 88 patients (2.2%) who received 60 to 80 Gy (time ratio = 1.37, 95% confidence interval: 1.11-1.69, p  = 0.003)., Conclusions: One-third of the patients with metastatic stage IV esophageal cancer in the National Cancer Database received esophageal radiation. Most received a radiation dose that, although consistent with palliative regimens, was not associated with a survival advantage. Further study is warranted to understand the indications for radiation in stage IV esophageal cancer and potentially reevaluate the most appropriate radiation dose for palliation., (© 2022 The Authors.)

Introduction: Metastatic involvement of at least one nonregional lymph node currently renders patients with esophageal cancer as having stage IV disease. However, the management and outcomes of patients whose sole determinant of stage IV status is nonregional lymph nodes (abbreviated as "stage IV-nodal" disease) have not been fully characterized., Methods: In this retrospective cohort study, the National Cancer Database was queried to identify patients 18 years of age or older who were diagnosed with stage IV esophageal cancer between 2016 and 2019. Survival was assessed by Kaplan-Meier analysis and Cox models in the overall sample and a propensity-matched sample. Patients with "stage IV-nodal" disease were compared with patients with systemic metastases involving a single organ or multiple organs., Results: Overall, 11,589 patients with clinical stage IV esophageal cancer were identified, including 1331 (11.5%) patients with stage IV-nodal disease. Patients with stage IV-nodal disease were more likely to receive chemotherapy (77%) than those with single systemic organ metastases (64%) and multiorgan metastases (63%) ( p < 0.0001); patients with stage IV-nodal disease were also more likely to receive radiation (49%) than those with single systemic organ metastases (40%) and multiorgan metastases (39%) ( p < 0.0001). Squamous cell carcinoma (OR = 1.58, 95% confidence interval [CI]: 1.34-1.86, p < 0.0001) and academic facility type (OR = 1.24, 95% CI: 1.09-1.4, p  = 0.0009) were associated with higher likelihood of the stage IV-nodal presentation. Patients with stage IV-nodal disease experienced superior survival (hazard ratio = 0.72, 95% CI: 0.66-0.78, p < 0.0001) than those with stage IV-single systemic metastases (reference group) and stage IV-multiorgan disease (hazard ratio = 1.30, 95% CI: 1.24-1.37)., Conclusions: Approximately 12% of patients with stage IV esophageal cancer lack systemic metastases at presentation. These patients with stage IV-nodal disease are more likely to receive treatment and experience superior survival. Further study of the stage IV-nodal population and consideration of a potential stage IV subclassification system is justified., (© 2022 The Authors.)

Importance: The 2017 international PACIFIC trial established a role for immunotherapy after chemoradiation for unresectable stage III non-small cell lung cancer (NSCLC). However, in the US, patients with NSCLC commonly differ from clinical trial populations in terms of age, health, access to care, and treatment course, which may all factor into the efficacy of immunotherapy., Objective: To determine the outcomes of immunotherapy use in unresectable stage III NSCLC in the general US population., Design, Setting, and Participants: This cohort study analyzed the National Cancer Database for patients diagnosed with clinical stage III NSCLC between 2015 and 2017 with follow-up through the end of 2018 who were treated with chemotherapy and radiation. Data were analyzed January 2022., Main Outcomes and Measures: Mortality hazard in a multivariable Cox proportional hazards model and survival among a propensity-matched sample treated with chemotherapy and radiation, with and without immunotherapy., Results: A total of 23 811 patients with clinical stage III NSCLC with median (IQR) age 66 (59-72) years met inclusion criteria (10 454 [43.9%] women; 564 [2.4%] Asian, 2930 [12.3%] Black, 20 077 [84.3%] White patients), including 209 (16.1%) patients with multiple comorbidities and 1297 (5.4%) immunotherapy recipients. Immunotherapy after chemotherapy and radiation was associated with reduced mortality (hazard ratio [HR], 0.74; 95% CI, 0.67-0.82; P < .001). Among a propensity-matched sample, immunotherapy was associated with superior 3-year survival (52% [1297 patients at 0 months, 56 patients at 36 months] vs 44% [2594 patients at 0 months, 173 patients at 36 months]; P < .001). The treatment of 833 patients who received immunotherapy (64.2%) differed from the PACIFIC trial protocol, including 221 patients (17.0%) who received radiation doses outside of the protocol range and 731 patients (56.4%) who started immunotherapy more than 6 weeks after radiation was completed. The survival advantage of immunotherapy persisted when initiated up to 12 weeks after radiation was completed (HR, 0.75; 95% CI, 0.61-0.92). Among patients who received radiation outside the PACIFIC protocol range, the survival advantage of immunotherapy was not significant (HR, 0.87; 95% CI, 0.69-1.01)., Conclusions and Relevance: In this cohort study, immunotherapy after chemotherapy and radiation for stage III NSCLC was associated with a survival advantage in the general US population despite two-thirds of patients treated differently than the PACIFIC protocol. The findings suggest there may be flexibility in the timing of immunotherapy initiation after radiation; further study is warranted to clarify the clinical benefits of immunotherapy.

Objective: Up to 40% of lobectomies are complicated by adverse events. Gastroesophageal reflux disease (GERD) and hiatal hernia have been associated with morbidity across a range of clinical scenarios, yet their relation to recovery from pulmonary resection is understudied. We evaluated GERD and hiatal hernia as predictors of complications after lobectomy for lung cancer., Methods: Lobectomy patients at Yale-New Haven Hospital between January 2014 and April 2021 were evaluated for predictors of 30-day postoperative complications, pneumonia, atrial arrhythmia, readmission, and mortality. Multivariable regression models included sociodemographic characteristics, body mass index, surgical approach, cardiopulmonary comorbidities, hiatal hernia, GERD, and preoperative acid-suppressive therapy as predictors., Results: Overall, 824 patients underwent lobectomy, including 50.5% with a hiatal hernia and 38.7% with GERD. The median age was 68 [interquartile range, 61-74] years, and the majority were female (58.4%). At least 1 postoperative complication developed in 39.6% of patients, including atrial arrhythmia (11.7%) and pneumonia (4.1%). Male sex (odds ratio [OR], 1.51; 95% confidence interval [CI], 1.11-2.06, P  = .01), age ≥70 years (OR, 1.55; 95% CI, 1.13-2.11, P  = .01), hiatal hernia (OR, 1.40; 95% CI, 1.03-1.90, P  = .03), and intraoperative packed red blood cells (OR, 4.80; 95% CI, 1.51-15.20, P  = .01) were significant risk factors for developing at least 1 postoperative complication. Hiatal hernia was also a significant predictor of atrial arrhythmia (OR, 1.64; 95% CI, 1.02-2.62, P  = .04) but was not associated with other adverse events., Conclusions: Our findings indicate that hiatal hernia may be a novel risk factor for complications, especially atrial arrhythmia, following lobectomy that should be considered in the preoperative evaluation of lung cancer patients., (© 2022 The Author(s).)

Importance: Clinical trials and compassionate use agreements provide selected patients with access to potentially life-saving treatments before approval by the Food and Drug Administration (FDA). Approval from the FDA decreases a number of access barriers; however, it is unknown whether FDA approval is associated with increases in the equitable use of novel therapies and reductions in disparities in use among patients with cancer in the US., Objective: To assess the association between FDA drug approval and disparities in the use of immunotherapy across health, sociodemographic, and socioeconomic strata before and after approval of the first checkpoint inhibitors for the treatment of patients with cancer in the US., Design, Setting, and Participants: This cohort study used data from the National Cancer Database to examine the use of immunotherapy across health, sociodemographic, and socioeconomic strata before and after FDA approval of the first checkpoint inhibitor therapies. A total of 402 689 patients 20 years or older who were diagnosed with stage IV non-small cell lung cancer (NSCLC), renal cell carcinoma (RCC), or melanoma of the skin between January 1, 2007, and December 31, 2018 (specific years varied by tumor type), were included., Exposures: Patient health (Charlson-Deyo comorbidity score and age), sociodemographic characteristics (sex, race, and ethnicity), and socioeconomic (insurance status and household income based on zip code of residence) characteristics., Main Outcomes and Measures: The association of patient characteristics with receipt of immunotherapy was evaluated in the 4 years before and the 3 years immediately after FDA approval using multivariable logistic regression modeling., Results: Among 402 689 patients (median [IQR] age, 68 [60-76 years]; 225 081 men [55.9%]), 347 233 had NSCLC, 43 714 had RCC, and 11 742 patients had melanoma. A total of 47 527 patients (11.8%) were Black, 15 763 (3.9%) were Hispanic, 375 874 (93.3%) were non-Hispanic, 335 833 (83.4%) were White, and 16 553 (4.1%) were of other races. Before FDA approval, 6271 patients (3.2%) with NSCLC, 1155 patients (4.8%) with RCC, and 504 patients (8.6%) with melanoma received immunotherapy compared with 23 908 patients (15.6%) with NSCLC, 3890 patients (19.7%) with RCC, and 1143 patients (19.3%) with melanoma after FDA approval. Before FDA approval, sociodemographic and socioeconomic characteristics were associated with variable immunotherapy administration by tumor type. For example, among those with NSCLC, Black patients were less likely to receive immunotherapy than White patients (odds ratio [OR], 0.78; 95% CI ,0.71-0.85; P < .001); among those with RCC, uninsured patients were less likely to receive immunotherapy than privately insured patients (OR, 0.31; 95% CI, 0.20-0.48; P < .001). After FDA approval, most disparities persisted, but several narrowed (eg, Black patients with NSCLC: OR, 0.87 [95% CI, 0.83-0.91; P < .001]; uninsured patients with RCC: OR, 0.60 [95% CI, 0.48-0.75; P < .001]). Although many disparities remained, some gaps across socioeconomic characteristics appeared to widen (eg, patients with NSCLC in the lowest vs highest income quartile: OR, 0.80; 95% CI, 0.76-0.83; P < .001), and new gaps emerged (eg, Black patients with RCC: OR, 0.82; 95% CI, 0.72-0.93; P = .003)., Conclusions and Relevance: In this cohort study, disparities in immunotherapy use existed across a number of sociodemographic and socioeconomic characteristics among patients with NSCLC, RCC, and melanoma before FDA approval, including during the important period when clinical trials were accruing patients. Although FDA approval was associated with a significant increase in the use of immunotherapy, gaps persisted, suggesting that FDA approval may not eliminate disparities in the use of novel therapies.

Introduction: Available guidelines are inconsistent as to whether patients with newly diagnosed clinical stage II NSCLC should receive routine brain imaging., Methods: The National Cancer Database was queried for the prevalence of isolated brain metastases among patients with newly diagnosed NSCLC in 2016 and 2017. Patients with metastases in locations other than the brain were excluded. The prevalences were then stratified by clinical T and N classifications and further stratified into a summary stage, which was calculated based on T and N classifications. The summary stage represents the clinical stage that would have been available at the time of decision for brain imaging., Results: A total of 6,949 of 149,958 patients (4.6%) with clinical stages I, II, III, or brain-limited stage IV NSCLC had dissemination limited to the brain. As T and N stages increased, prevalence of brain metastases generally increased. Among patients with node-negative (N0) NSCLC, the prevalence of brain-only metastases increased from 1.2% in patients with T1a to 3.8% among patients with T4 ( p < 0.001). Among patients with T1a, the prevalence of brain-only metastases increased from 1.2% for patients with N0 to 7.9% for patients with N3 ( p < 0.001). The prevalence of brain-limited metastases generally increased with increasing summary stage. The prevalence of brain-only metastases among patients with stage IA was 1.7% whereas that among patients with stage IIIA was 6.7% ( p < 0.001). Of note, the prevalence of brain-limited metastases was approximately 6% for both summary stages II and III., Conclusions: Considering the similarity in prevalence of isolated brain metastases and the potential hazards associated with brain imaging in early stage NSCLC, practitioners may consider a more liberal use of brain imaging when interpreting conflicting guidelines., (© 2022 The Authors.)

Importance: Insurance status has been linked to important differences in cancer treatment and outcomes in the US. With more than 15 million individuals gaining health insurance through Medicaid expansion, there is an increasing need to understand the implications of this policy within the US cancer population. This review provides an overview of the fundamental principles and nuances of Medicaid expansion, as well as the implications for cancer care., Observations: The Patient Protection and Affordable Care Act presented states with an option to expand Medicaid coverage by broadening the eligibility criteria (eg, raising the eligible income level). During the past 10 years, Medicaid expansion has been credited with a 30% reduction in the population of uninsured individuals in the US. Such a significant change in the insurance profile could have important implications for the 1.7 million patients diagnosed with cancer each year, the oncology teams that care for them, and policy makers. However, several factors may complicate efforts to characterize the effect of Medicaid expansion on the US cancer population. Most notably, there is considerable variation among states in terms of whether Medicaid expansion took place, when expansion occurred, eligibility criteria for Medicaid, and coverage types that Medicaid provides. In addition, economic and health policy factors may be intertwined with factors associated with Medicaid expansion. Finally, variability in the manner in which cancer care has been captured and depicted in large databases could affect the interpretation of findings associated with expansion., Conclusions and Relevance: The expansion of Medicaid was a historic public policy initiative. To fully leverage this policy to improve oncological care and to maximize learning for subsequent policies, it is critical to understand the effect of Medicaid expansion. This review aims to better prepare investigators and their audiences to fully understand the implications of this important health policy initiative.

Background: Non-communicable diseases (NCDs) are an increasing global concern, with morbidity and mortality largely occurring in low- and middle-income settings. We established the prospective Rural Uganda Non-Communicable Disease (RUNCD) cohort to longitudinally characterize the NCD prevalence, progression, and complications in rural Africa., Methods: We conducted a population-based census for NCD research. We systematically enrolled adults in each household among three sub-counties of the larger Nakaseke Health district and collected baseline demographic, health status, and self-reported chronic disease information. We present our data on self-reported chronic disease, as stratified by age, sex, educational attainment, and sub-county., Results: A total of 16,694 adults were surveyed with 10,563 (63%) respondents enrolled in the self-reported study. Average age was 37.8 years (SD = 16.5) and 45% (7481) were male. Among self-reported diseases, hypertension (HTN) was most prevalent (6.3%). 1.1% of participants reported a diagnosis of diabetes, 1.1% asthma, 0.7% COPD, and 0.4% kidney disease. 2.4% of the population described more than one NCD. Self-reported HTN was significantly higher in the peri-urban subcounty than in the other two rural sub-counties (p < 0.001); diagnoses for all other diseases did not differ significantly between sub-counties. Odds for self-reported HTN increased significantly with age (OR = 1.87 per 10 years of age, 95% CI 1.78-1.96). Male sex was associated with lower odds of reporting asthma (OR = 0.53, 95% CI 0.34-0.82) or HTN (OR = 0.31, 95% CI 0.26-0.40)., Conclusions: The RUNCD will establish one of the largest NCD patient cohorts in rural Africa. First analysis highlights the feasibility of systematically enrolling large numbers of adults living in a rural Ugandan district. In addition, our study demonstrates low levels of self-reported NCDs compared to the nation-wide established levels, emphasizing the need to better educate, characterize, and care for the majority of rural communities., (© 2021. The Author(s).)

Background: The clinical significance of accumulating toxic terminal metabolites such as oxalate in patients with kidney failure is not well understood., Methods: To evaluate serum oxalate concentrations and risk of all-cause mortality and cardiovascular events in a cohort of patients with kidney failure requiring chronic dialysis, we performed a post-hoc analysis of the randomized German Diabetes Dialysis (4D) Study; this study included 1255 European patients on hemodialysis with diabetes followed-up for a median of 4 years. The results obtained via Cox proportional hazards models were confirmed by competing risk regression and restricted cubic spline modeling in the 4D Study cohort and validated in a separate cohort of 104 US patients on dialysis after a median follow-up of 2.5 years., Results: A total of 1108 patients had baseline oxalate measurements, with a median oxalate concentration of 42.4 µM. During follow-up, 548 patients died, including 139 (25.4%) from sudden cardiac death. A total of 413 patients reached the primary composite cardiovascular end point (cardiac death, nonfatal myocardial infarction, and fatal or nonfatal stroke). Patients in the highest oxalate quartile (≥59.7 µM) had a 40% increased risk for cardiovascular events (adjusted hazard ratio [aHR], 1.40; 95% confidence interval [95% CI], 1.08 to 1.81) and a 62% increased risk of sudden cardiac death (aHR, 1.62; 95% CI, 1.03 to 2.56), compared with those in the lowest quartile (≤29.6 µM). The associations remained when accounting for competing risks and with oxalate as a continuous variable., Conclusions: Elevated serum oxalate is a novel risk factor for cardiovascular events and sudden cardiac death in patients on dialysis. Further studies are warranted to test whether oxalate-lowering strategies improve cardiovascular mortality in patients on dialysis., (Copyright © 2021 by the American Society of Nephrology.)

Introduction: Patients with early-stage NSCLC typically must choose between a surgery with superior local control (lobectomy) or one that preserves lung parenchyma (wedge). Recognizing that many patients with cancer have competing mortality risks unrelated to cancer, we investigated whether an established model of predicting life expectancy could be used to identify patients with stage I NSCLC for whom survival after wedge is not different from lobectomy., Methods: A retrospective cohort study using the National Cancer Institute's Surveillance Epidemiology and End Results-Medicare was performed to evaluate survival among treatment-naive patients, diagnosed 2005-2015, who underwent lobectomy or wedge for stage I (≤2 cm tumors) NSCLC. Comorbidity-related life expectancy (CR-LE) was estimated using a standard life-table approach based on comorbid conditions, sex, and age. Cox models and perioperative complications were stratified by 5-year CR-LE., Results: A total of 4560 patients (median age 74, interquartile range 70-78) were identified. CR-LE was greater than or equal to 5 years for 4016 patients (wedge = 23%). CR-LE was less than 5 years for 544 patients (wedge = 41%). Among patients with CR-LE greater than or equal to 5, wedge resection was associated with higher risk of mortality than lobectomy (hazard ratio: 1.68, 95% confidence interval: 1.52-1.86, p < 0.001). For those with CR-LE less than 5, there was no significant difference in mortality risk between lobectomy and wedge (hazard ratio: 1.19, 95% confidence interval: 0.96-1.47; p  = 0.11). CR-LE less than five patients who underwent a lobectomy had higher 90-day mortality compared with wedge (9% versus 4%, p  = 0.04)., Conclusion: The survival advantage of lobectomy over wedge for stage I NSCLC seems to dissipate among patients with shorter life expectancy owing to age and comorbidities. Wedge resection may be a reasonable option for patients at high risk of dying from non-cancer-related causes., (© 2021 The Authors.)

Objective: The outcomes of patients treated on the COVID-minimal pathway were evaluated during a period of surging COVID-19 hospital admissions, to determine the safety of continuing to perform urgent operations during the pandemic., Summary of Background Data: Crucial treatments were delayed for many patients during the COVID-19 pandemic, over concerns for hospital-acquired COVID-19 infections. To protect cancer patients whose survival depended on timely surgery, a "COVID-minimal pathway" was created., Methods: Patients who underwent a surgical procedure on the pathway between April and May 2020 were evaluated. The "COVID-minimal surgical pathway" consisted of: (A) evolving best-practices in COVID-19 transmission-reduction, (B) screening patients and staff, (C) preoperative COVID-19 patient testing, (D) isolating pathway patients from COVID-19 patients. Patient status through 2 weeks from discharge was determined as a reflection of hospital-acquired COVID-19 infections., Results: After implementation, pathway screening processes excluded 7 COVID-19-positive people from interacting with pathway (4 staff and 3 patients). Overall, 122 patients underwent 125 procedures on pathway, yielding 83 admissions (42 outpatient procedures). The median age was 64 (56-79) and 57% of patients were female. The most common surgical indications were cancer affecting the uterus, genitourinary tract, colon, lung or head and neck. The median length of admission was 3 days (1-6). Repeat COVID-19 testing performed on 27 patients (all negative), including 9 patients evaluated in an emergency room and 8 readmitted patients. In the postoperative period, no patient developed a COVID-19 infection., Conclusions: A COVID-minimal pathway comprised of physical space modifications and operational changes may allow urgent cancer treatment to safely continue during the COVID-19 pandemic, even during the surge-phase.

Importance: Tumor size larger than 4 cm is accepted as an indication for adjuvant chemotherapy in patients with node-negative non-small cell lung cancer (NSCLC). Treatment guidelines suggest that high-risk features are also associated with the efficacy of adjuvant chemotherapy among patients with early-stage NSCLC, yet this association is understudied., Objective: To assess the association between adjuvant chemotherapy and survival in the presence and absence of high-risk pathologic features in patients with node-negative early-stage NSCLC., Design, Setting, and Participants: This retrospective cohort study using data from the National Cancer Database included 50 814 treatment-naive patients with a completely resected node-negative NSCLC diagnosed between January 1, 2010, and December 31, 2015. The study was limited to patients who survived at least 6 weeks after surgery (ie, estimated median time to initiate adjuvant chemotherapy after surgery) to mitigate immortal time bias. Statistical analysis was performed from December 1, 2018, to February 29, 2020., Exposures: Adjuvant chemotherapy use vs observation, stratified according to the presence or absence of high-risk pathologic features (visceral pleural invasion, lymphovascular invasion, and high-grade histologic findings), sublobar surgery, and tumor size., Main Outcomes and Measures: The association of high-risk pathologic features with survival after adjuvant chemotherapy vs observation was evaluated using Cox proportional hazards regression models., Results: Overall, 50 814 eligible patients with NSCLC (27 365 women [53.9%]; mean [SD] age, 67.4 [9.5] years]) were identified, including 4220 (8.3%) who received adjuvant chemotherapy and 46 594 (91.7%) who did not receive adjuvant chemotherapy. Among patients with tumors 3 cm or smaller, chemotherapy was not associated with improved survival (hazard ratio [HR], 1.10; 95% CI, 0.96-1.26; P = .17). For patients with tumors larger than 3 cm to 4 cm, adjuvant chemotherapy was associated with a survival benefit among patients who underwent sublobar surgery (HR, 0.72; 95% CI, 0.56-0.93; P = .004). For tumors larger than 4 cm to 5 cm, a survival benefit was associated with adjuvant chemotherapy only in patients with at least 1 high-risk pathologic feature (HR, 0.67; 95% CI, 0.56-0.80; P = .02). For tumors larger than 5 cm, adjuvant chemotherapy was associated with a survival benefit irrespective of the presence of high-risk pathologic features (HR, 0.75; 95% CI, 0.61-0.91; P = .004)., Conclusions and Relevance: In this cohort study, tumor size alone was not associated with improved efficacy of adjuvant chemotherapy in patients with early-stage (node-negative) NSCLC. High-risk clinicopathologic features and tumor size should be considered simultaneously when evaluating patients with early-stage NSCLC for adjuvant chemotherapy.

Introduction: Calcium oxalate supersaturation is regularly exceeded in the plasma of patients with end-stage renal disease (ESRD). Previous reports have indicated that hemodialfiltration (HDF) lowers elevated plasma oxalate (P Ox ) concentrations more effectively compared with hemodialysis (HD). We reevaluate the therapeutic strategy for optimized P Ox reduction with advanced dialysis equipment and provide data on the effect of extended treatment time on dialytic oxalate kinetics., Methods: Fourteen patients with ESRD who underwent HDF 3 times a week for 4 to 4.5 hours (regular HDF; n = 8) or 7 to 7.5 hours (extended HDF; n = 6) were changed to HD for 2 weeks and then back to HDF for another 2 weeks. P Ox was measured at baseline, pre-, mid-, and postdialysis, and 2 hours after completion of the treatment session., Results: Baseline P Ox for all patients averaged 28.0 ± 7.0 μmol/l. Intradialytic P Ox reduction was approximately 90% and was not significantly different between groups or treatment modes [F(1) = 0.63; P  = 0.44]. Mean postdialysis P Ox concentrations were 3.3 ± 1.8 μmol/l. A rebound of 2.1 ± 1.9 μmol/l was observed within 2 hours after dialysis. After receiving 2 weeks of the respective treatment, predialysis P Ox concentrations on HD did not differ significantly from those on HDF [F(1) = 0.21; P  = 0.66]. Extended treatment time did not provide any added benefit [F(1) = 0.76; P  = 0.40]., Discussion: In contrast to earlier observations, our data did not support a benefit of HDF over HD for P Ox reduction. With new technologies evolving, our results emphasized the need to carefully reevaluate and update traditional therapeutic regimens for optimized uremic toxin removal, including those used for oxalate.

Purpose of Review: Oxalate is an end product of metabolism excreted via the kidney. Excess urinary oxalate, whether from primary or enteric hyperoxaluria, can lead to oxalate deposition in the kidney. Oxalate crystals are associated with renal inflammation, fibrosis, and progressive renal failure. It has long been known that as the glomerular filtration rate becomes reduced in chronic kidney disease (CKD), there is striking elevation of plasma oxalate. Taken together, these findings raise the possibility that elevation of plasma oxalate in CKD may promote renal inflammation and more rapid progression of CKD independent of primary cause., Recent Findings: The inflammasome has recently been identified to play a critical role in oxalate-induced renal inflammation. Oxalate crystals have been shown to activate the NOD-like receptor family, pyrin domain containing 3 inflammasome (also known as NALP3, NLRP3, or cryopyrin), resulting in release of IL-1β and macrophage infiltration. Deletion of inflammasome proteins in mice protects from oxalate-induced renal inflammation and progressive renal failure., Summary: The findings reviewed in this article expand our understanding of the relevance of elevated plasma oxalate levels leading to inflammasome activation. We propose that inhibiting oxalate-induced inflammasome activation, or lowering plasma oxalate, may prevent or mitigate progressive renal damage in CKD, and warrants clinical trials.