Initial management and survival of patients with primary metastatic bladder cancer before the immunotherapy era: a population-based study from Norway.

Before immunotherapy became part of the management of metastatic bladder cancer (mBC), systemic anti-cancer treatment comprised primarily of platinum-based chemotherapy. The objective of this study was to describe the characteristics, the initial management, overall survival (OS) and hospitalisations of patients with mBC before 2018 when immunotherapy for mBC was introduced in Norway.  Material and methods: It is a nationwide population-based study of primary mBC patients (diagnosed 2008-16). Descriptive statistics were applied and stratified for four initial management options (≤150 days after BC diagnosis): chemotherapy, major local treatment (cystectomy/pelvic radiotherapy), multimodal treatment (chemotherapy and local) and no anti-cancer treatment beyond transurethral resection of bladder tumour (untreated). Group differences were evaluated by Chi-square and Kruskal-Wallis test; OS was estimated with Kaplan-Meier. Results: Of the 305 patients included, 76 (25%) patients had chemotherapy, 46 (15%) patients had major local treatment, 21 (7%) patients had multimodal treatment and 162 (53%) patients were untreated.  Median OS ranged from 2.3 months (untreated) to 9.8 months (chemotherapy). Patients who received treatment had a higher rate of hospitalisation, with a median stay of three to four times that of untreated patients. Conclusion: Before immunotherapy, more than 50% of patients with primary mBC did not receive any initial anti-cancer therapy and had a poor survival. Patients treated with chemotherapy had inferior median OS compared to those treated with comparable systemic strategies in contemporary trials. Our results provide a basis for future research on treatment and survival after the introduction of immunotherapy for mBC, aiming to improve the care and outcome of patients with mBC.

A novel score of IL-13 and age predicts 90-day mortality in severe alcohol-associated hepatitis: A multicenter plasma biomarker analysis.

BACKGROUND: Severe alcoholic hepatitis (AH) has a high short-term mortality rate. The MELD assesses disease severity and mortality; however, it is not specific for AH. We screened plasma samples from patients with severe AH for biomarkers of multiple pathological processes and identified predictors of short-term mortality. METHODS: Plasma was collected at baseline from 85 patients with severe AH (MELD≥20, Maddrey's discriminant function≥32) enrolled in the Defeat Alcoholic Steatohepatitis clinical trial (investigating IL-1 receptor antagonist+pentoxifylline+zinc vs. methylprednisolone+placebo). Samples were analyzed for 43 biomarkers and the markers' association with 28- and 90-day mortalities was assessed. RESULTS: Thirty-one (36.5%) patients died during the 90-day follow-up with similar ratios in the treatment groups. Eight biomarkers showed an association with mortality. IL-6, IL-22, interferon-α2, soluble TNF receptor 1, lipocalin-2, and α-fetoprotein levels were associated with 28-day mortality, while IL-6, IL-13, and endotoxin levels with 90-day mortality. In multivariable Cox regression, encephalopathy, lipocalin-2, and α-fetoprotein levels were independent predictors of 28-day mortality, and IL-6, IL-13, international normalized ratio levels, and age were independent predictors of 90-day mortality. The combination of IL-13 and age had superior performance in predicting 90-day mortality compared with MELD in the total cohort and the individual treatment groups. CONCLUSIONS: We identified predictors of short-term mortality in a cohort exclusively involving patients with severe AH. We created a composite score of IL-13 and age that predicts 90-day mortality regardless of the treatment type with a performance superior to MELD in severe AH.

Nonbiological factors affecting outcomes in adolescents and young adults with lymphoma.

The impact of nonbiological factors (NBF) on survival was investigated in a large cohort of adolescents and young adults (AYA) with lymphoma in the United States (US). We found that uninsured and Medicaid AYA beneficiaries with classical Hodgkin lymphoma (cHL) and non-Hodgkin lymphoma (NHL) are at significantly increased risk of death when compared with their insured counterpart even after adjustment for other factors affecting survival. Increased risk of death was also noted for Non-Hispanic Black (NHB) patients with cHL and NHL when compared to Non-Hispanic White (NHW) patients, however, only Hispanic patients with NHL were found to have a significantly increased mortality risk while those with cHL were not. NHL AYA patients residing in lower-income counties are at increased risk of death. The strong association of NBF with survival indicates opportunities to improve the survival of AYA lymphoma patients by improving access/quality of care in the US.

Opportunities, challenges, and future directions for simulation modeling the effects of structural racism on cancer mortality in the United States: a scoping review.

PURPOSE: Structural racism could contribute to racial and ethnic disparities in cancer mortality via its broad effects on housing, economic opportunities, and health care. However, there has been limited focus on incorporating structural racism into simulation models designed to identify practice and policy strategies to support health equity. We reviewed studies evaluating structural racism and cancer mortality disparities to highlight opportunities, challenges, and future directions to capture this broad concept in simulation modeling research. METHODS: We used the Preferred Reporting Items for Systematic Reviews and Meta-Analyses-Scoping Review Extension guidelines. Articles published between 2018 and 2023 were searched including terms related to race, ethnicity, cancer-specific and all-cause mortality, and structural racism. We included studies evaluating the effects of structural racism on racial and ethnic disparities in cancer mortality in the United States. RESULTS: A total of 8345 articles were identified, and 183 articles were included. Studies used different measures, data sources, and methods. For example, in 20 studies, racial residential segregation, one component of structural racism, was measured by indices of dissimilarity, concentration at the extremes, redlining, or isolation. Data sources included cancer registries, claims, or institutional data linked to area-level metrics from the US census or historical mortgage data. Segregation was associated with worse survival. Nine studies were location specific, and the segregation measures were developed for Black, Hispanic, and White residents. CONCLUSIONS: A range of measures and data sources are available to capture the effects of structural racism. We provide a set of recommendations for best practices for modelers to consider when incorporating the effects of structural racism into simulation models.

Toripalimab Plus Chemotherapy for Recurrent or Metastatic Nasopharyngeal Carcinoma: The JUPITER-02 Randomized Clinical Trial.

Importance: There are currently no therapies approved by the US Food and Drug Administration for nasopharyngeal carcinoma (NPC). Gemcitabine-cisplatin is the current standard of care for the first-line treatment of recurrent or metastatic NPC (RM-NPC). Objective: To determine whether toripalimab in combination with gemcitabine-cisplatin will significantly improve progression-free survival and overall survival as first-line treatment for RM-NPC, compared with gemcitabine-cisplatin alone. Design, Setting, and Participants: JUPITER-02 is an international, multicenter, randomized, double-blind phase 3 study conducted in NPC-endemic regions, including mainland China, Taiwan, and Singapore. From November 10, 2018, to October 20, 2019, 289 patients with RM-NPC with no prior systemic chemotherapy in the RM setting were enrolled from 35 participating centers. Interventions: Patients were randomized (1:1) to receive toripalimab (240 mg [n = 146]) or placebo (n = 143) in combination with gemcitabine-cisplatin for up to 6 cycles, followed by maintenance with toripalimab or placebo until disease progression, intolerable toxicity, or completion of 2 years of treatment. Main Outcome: Progression-free survival as assessed by a blinded independent central review. Secondary end points included objective response rate, overall survival, progression-free survival assessed by investigator, duration of response, and safety. Results: Among the 289 patients enrolled (median age, 46 [IQR, 38-53 years; 17% female), at the final progression-free survival analysis, toripalimab treatment had a significantly longer progression-free survival than placebo (median, 21.4 vs 8.2 months; HR, 0.52 [95% CI, 0.37-0.73]). With a median survival follow-up of 36.0 months, a significant improvement in overall survival was identified with toripalimab over placebo (hazard ratio [HR], 0.63 [95% CI, 0.45-0.89]; 2-sided P = .008). The median overall survival was not reached in the toripalimab group, while it was 33.7 months in the placebo group. A consistent effect on overall survival, favoring toripalimab, was found in subgroups with high and low PD-L1 (programmed death-ligand 1) expression. The incidence of all adverse events, grade 3 or greater adverse events, and fatal adverse events were similar between the 2 groups. However, adverse events leading to discontinuation of toripalimab or placebo (11.6% vs 4.9%), immune-related adverse events (54.1% vs 21.7%), and grade 3 or greater immune-related adverse events (9.6% vs 1.4%) were more frequent in the toripalimab group. Conclusions and Relevance: The addition of toripalimab to chemotherapy as first-line treatment for RM-NPC provided statistically significant and clinically meaningful progression-free survival and overall survival benefits compared with chemotherapy alone, with a manageable safety profile. These findings support the use of toripalimab plus gemcitabine-cisplatin as the new standard of care for this patient population. Trial Registration: ClinicalTrials.gov Identifier: NCT03581786.

Explaining COVID-19 related mortality disparities in American Indians and Alaska Natives.

American Indian and Alaska Native (AI/AN) individuals are more likely to die with COVID-19 than other groups, but there is limited empirical evidence to explain the cause of this inequity. The objective of this study was to determine whether medical comorbidities, area socioeconomic deprivation, or access to treatment can explain the greater COVID-19 related mortality among AI/AN individuals. The design was a retrospective cohort study of harmonized electronic health record data of all inpatients with COVID-19 from 21 United States health systems from February 2020 through January 2022. The mortality of AI/AN inpatients was compared to all Non-Hispanic White (NHW) inpatients and to a matched subsample of NHW inpatients. AI/AN inpatients were more likely to die during their hospitalization (13.2% versus 7.1%; odds ratio [OR] = 1.98, 95% confidence interval [CI] = 1.48, 2.65) than their matched NHW counterparts. After adjusting for comorbidities, area social deprivation, and access to treatment, the association between ethnicity and mortality was substantially reduced (OR 1.59, 95% CI 1.15, 2.22). The significant residual relation between AI/AN versus NHW status and mortality indicate that there are other important unmeasured factors that contribute to this inequity. This will be an important direction for future research.

Dietary saturated fatty acids increased all-cause and cardiovascular disease mortality in an elderly population: The National Health and Nutrition Examination Survey.

The influence of dietary saturated fatty acids intake on human health and cardiovascular disease (CVD) remains debated. The aim of this study was to explore the association between dietary saturated fatty acid consumption and all-cause and CVD mortality among the elderly population. Data for the participants in this study were obtained from the National Health and Nutrition Examination Survey dataset spanning the years 2003 through 2008. Information regarding mortality and the follow-up duration were extracted from the 2019 public-use linked mortality files provided by the National Center for Health Statistics. A total of 3404 participants were included in this study. The ratio of dietary saturated fatty acids to total fat was associated with the mortality from all-cause, heart disease, and cerebrovascular disease after adjusting confounding factors (P < .05). For every 10% increase in the saturated fatty acids to total fat ratio, all-cause mortality increased by 24% (hazard ratio [HR], 1.24; 95% confidence interval [CI], 1.13-1.37), the heart disease mortality increased by 26% (HR, 1.26; 95% CI, 1.05-1.52), and the cerebrovascular disease mortality increased by 67% (HR, 1.67; 95% CI, 1.14-2.45) at 10 years' follow-up. In addition, low dietary saturated fatty acids intake was associated with reduced mortality because of all-cause and heart disease after adjusting confounding factors (P < .05). In conclusion, in this elderly population, dietary saturated fatty acid intake was associated with all-cause mortality, heart disease mortality, and cerebrovascular disease mortality. Reducing saturated fatty acid intake in the diet may extend the survival rate for the elderly population. However, the difference of the effects of specific dietary saturated fatty acids with different chain lengths on mortality needs further study.

Mortality trend due to chronic kidney disease in Brazil: an ecological study.

OBJECTIVE: To analyze chronic kidney disease mortality in Brazil according to sex, age group and region of residence, from 2009 to 2020. METHODS: This was a time series study having deaths as its unit of analysis, based on Mortality Information System data. The mortality rate was standardized using the direct method and the temporal trend was analyzed using the Prais-Winsten method. RESULTS: There was a rising trend in chronic kidney disease mortality, ranging from 2.82, in 2009, to 3.24 in 2020 (average annual increase 1.29%; 95%CI 0.73;1.85), with a greater increase in males (1.14% per year; 95%CI 0.52;1.76), those aged 75 years and over (2.23% per year; 95%CI 1.87; 2.60) and in the Northern Region (3.86% per year; 95%CI 1.86;5.90) and Northeast Region (3.36% per year; 95%CI 2.24;4.50). CONCLUSION: Chronic kidney disease mortality showed a rising trend in the period, with sociodemographic disparities. MAIN RESULTS: A rising mortality trend was found for both sexes, with a greater increase in males, those aged over 75 years and in the North and Northeast regions of Brazil; mortality was highest in the Midwest region throughout the entire period. IMPLICATIONS FOR SERVICES: The results point to the need to implement public policies with guidelines for addressing chronic kidney disease, focused on strengthening Primary Health Care (PHC). PERSPECTIVES: Expanding access to health services, health education and integration between PHC, health surveillance and specialized care are strategies that would possibly prove to be efficient in managing this chronic health condition.

Snakebites in Northeastern Brazil: accessing clinical-epidemiological profile as a strategy to deal with Neglected Tropical Diseases.

BACKGROUND: Brazil ranks first in the number of snakebites in South America. A detailed analysis of these cases is required to improve the public health planning. In this study, we retrospectively examined the clinical and epidemiological profiles of snakebites in Maranhão between January 2009 and December 2019. METHODS: Data were obtained from the compulsory notification forms provided by the Health Department of Maranhão. RESULTS: A total of 17,658 cases were recorded during the study period. Most of the bites were from snakes belonging to the genus Bothrops. Medical care was mostly within three hours after the bite. Most cases were classified as mild and most victims recovered; however, 139 deaths were recorded. Most bites occurred among people aged 20-39 years, mainly among rural workers. The most frequent local clinical manifestations were pain, edema, and ecchymosis. The most common systemic clinical manifestations include neuroparalysis, vagal syndrome, and myolysis. Most snakebites occurred between January and March. The municipalities with the highest number of notifications were Buriticupu (936 cases), Arame (705 cases), and Grajaú (627 cases). CONCLUSIONS: The clinical profile of snakebites in Maranhão is similar to that observed in other states of Northeast Brazil. However, we found that some systemic manifestations are not compatible with the etiology of snakebites, which leads us to believe that the problem could be the lack of knowledge of the health professionals at the site of envenomation, who may not be ready for attendance, and an important lack of health centers with snake antivenom to treat snakebites.