Pharmacogenetics of DPYD and treatment-related mortality on fluoropyrimidine chemotherapy for cancer patients: a meta-analysis and trial sequential analysis.

BACKGROUND: Fluoropyrimidines are chemotherapy drugs utilized to treat a variety of solid tumors. These drugs predominantly rely on the enzyme dihydropyrimidine dehydrogenase (DPD), which is encoded by the DPYD gene, for their metabolism. Genetic mutations affecting this gene can cause DPYD deficiency, disrupting pyrimidine metabolism and increasing the risk of toxicity in cancer patients treated with 5-fluorouracil. The severity and type of toxic reactions are influenced by genetic and demographic factors and, in certain instances, can result in patient mortality. Among the more than 50 identified variants of DPYD, only a subset has clinical significance, leading to the production of enzymes that are either non-functional or impaired. The study aims to examine treatment-related mortality in cancer patients undergoing fluoropyrimidine chemotherapy, comparing those with and without DPD deficiency. METHODS: The meta-analysis selected and evaluated 9685 studies from Pubmed, Cochrane, Embase and Web of Science databases. Only studies examining the main DPYD variants (DPYD*2A, DPYD p.D949V, DPYD*13 and DPYD HapB3) were included. Statistical Analysis was performed using R, version 4.2.3. Data were examined using the Mantel-Haenszel method and 95% CIs. Heterogeneity was assessed with I2 statistics. RESULTS: There were 36 prospective and retrospective studies included, accounting for 16,005 patients. Most studies assessed colorectal cancer, representing 86.49% of patients. Other gastrointestinal cancers were evaluated by 11 studies, breast cancer by nine studies and head and neck cancers by five studies. Four DPYD variants were identified as predictors of severe fluoropyrimidines toxicity in literature review: DPYD*2A (rs3918290), DPYD p.D949V (rs67376798), DPYD*13 (rs55886062) and DPYD Hap23 (rs56038477). All 36 studies assessed the DPYD*2A variant, while 20 assessed DPYD p.D949V, 7 assessed DPYD*13, and 9 assessed DPYDHap23. Among the 587 patients who tested positive for at least one DPYD variant, 13 died from fluoropyrimidine toxicity. Conversely, in the non-carrier group there were 14 treatment-related deaths. Carriers of DPYD variants was found to be significantly correlated with treatment-related mortality (OR = 34.86, 95% CI 13.96-87.05; p < 0.05). CONCLUSIONS: This study improves our comprehension of how the DPYD gene impacts cancer patients receiving fluoropyrimidine chemotherapy. Identifying mutations associated with dihydropyrimidine dehydrogenase deficiency may help predict the likelihood of serious side effects and fatalities. This knowledge can be applied to adjust medication doses before starting treatment, thus reducing the occurrence of these critical outcomes.

Fatality from COVID-19 does not affect palliative care duration among patients with advanced cancer: a retrospective cohort study.

BACKGROUND: Jomar et al. demonstrated that death due to COVID-19 did not affect the time under exclusive palliative care among patients with advanced cancer, even during the first year of the pandemic caused by a hitherto little-known disease. BACKGROUND: ◼ Fatality due to COVID-19 does not alter the time under oncological palliative care. BACKGROUND: ◼ The retrospective design of this pioneering study allows causal inference. BACKGROUND: ◼ Access to oncological palliative care frequently approaches terminality of life. OBJECTIVE: This study aimed at investigating the extent to which COVID-19-induced fatalities affect the duration of palliative care among patients with advanced cancer. METHODS: A retrospective cohort study was conducted at the Palliative Care Unit of the Brazilian Instituto Nacional de Câncer in Rio de Janeiro, Brazil, on 1,104 advanced cancer patients who died under exclusive palliative care between March 11, 2020, and March 31, 2021. Wilcoxon rank-sum (Mann-Whitney U) and log-rank tests were performed to examine statistical differences between the medians of time, and the Kaplan-Meier estimator was used to graphically illustrate survival over time under exclusive palliative care contingent upon the underlying causes of death of the two experimental groups (cancer versus COVID-19). RESULTS: A total of 133 (12.05%) patients succumbed to COVID-19. In both groups, the median time under exclusive palliative care was less than one month. The exclusive palliative care survival curves did not exhibit any statistically significant difference between the groups. CONCLUSION: Death due to COVID-19 did not modify the duration of exclusive palliative care among patients with advanced cancer.

Biofilm formation and increased mortality among cancer patients with candidemia in a Peruvian reference center.

BACKGROUND: Candidemia is an invasive mycosis with an increasing global incidence and high mortality rates in cancer patients. The production of biofilms by some strains of Candida constitutes a mechanism that limits the action of antifungal agents; however, there is limited and conflicting evidence about its role in the risk of death. This study aimed to determine whether biofilm formation is associated with mortality in cancer patients with candidemia. METHODS: This retrospective cohort study included patients treated at Peru's oncologic reference center between June 2015 and October 2017. Data were collected by monitoring patients for 30 days from the diagnosis of candidemia until the date of death or hospital discharge. Statistical analyses evaluated the association between biofilm production determined by XTT reduction and mortality, adjusting for demographic, clinical, and microbiological factors assessed by the hospital routinary activities. Survival analysis and bivariate and multivariate Cox regression were used, estimating the hazard ratio (HR) as a measure of association with a significance level of p < 0.05. RESULTS: A total of 140 patients with candidemia were included in the study. The high mortality observed on the first day of post-diagnosis follow-up (81.0%) among 21 patients who were not treated with either antifungal or antimicrobial drugs led to stratification of the analyses according to whether they received treatment. In untreated patients, there was a mortality gradient in patients infected with non-biofilm-forming strains vs. low/medium and high-level biofilm-forming strains (25.0%, 66.7% and 82.3%, respectively, p = 0.049). In treated patients, a high level of biofilm formation was associated with increased mortality (HR, 3.92; 95% p = 0.022), and this association persisted after adjusting for age, comorbidities, and hospital emergency admission (HR, 6.59; CI: 1.87-23.24, p = 0.003). CONCLUSIONS: The association between candidemia with in vitro biofilm formation and an increased risk of death consistently observed both in patients with and without treatment, provides another level of evidence for a possible causal association. The presence of comorbidities and the origin of the hospital emergency, which reflect the fragile clinical condition of the patients, and increasing age above 15 years were associated with a higher risk of death.

Clinical and epidemiological factors related to mortality due to septic shock in a pediatric intensive care unit.

INTRODUCTION: Septic shock is a potentially life-threatening condition. The aim of this study was to identify clinical and epidemiological factors associated with mortality in pediatric patients admitted to a pediatric intensive care unit (PICU) with septic shock. MATERIALS AND METHODS: A retrospective comparative case series study was conducted with children aged 1 month to 14 years with septic shock from 2018 to 2020 in a PICU in Lima, Peru. Patients were divided into deceased and survivor groups based on their condition at discharge from the PICU. The influence of each variable on mortality was assessed using a logistic regression model. RESULTS: A total of 174 patients were included in the study, with 51 (29.3%) fatalities. Deceased patients, compared to survivors, were older, had a higher incidence of oncological disease (31.4% vs. 14.6%; p = 0.011), more frequently presented with hemoglobin ≤ 9 g/dL (44% vs. 28%; p = 0.043), lactate > 2 mmol/L (70% vs. 44%; p = 0.002), platelets ≤ 150 (×103)/µL (77% vs. 42%; p < 0.001), and pH ≤ 7.1 (31% vs. 6%; p < 0.001). In the logistic regression model, factors related to mortality were having a pH ≤ 7.1 (odds ratio [OR] = 8.95; 95% confidence interval [CI]: 2.52-31.75) and platelets ≤ 150 (×103)/µL (OR = 3.89; 95% CI: 1.40-10.84). CONCLUSIONS: Factors associated with mortality in pediatric patients with septic shock were a pH ≤ 7.1 and platelets ≤ 150 (×103)/µL in the assessments conducted upon admission to the PICU.

INTRODUCCIÓN: El shock séptico es una condición potencialmente mortal. El objetivo del estudio fue identificar factores clínicos y epidemiológicos relacionados con la mortalidad en pacientes que ingresaron por shock séptico a una Unidad de Cuidados Intensivos Pediátricos (UCIP). MÉTODOS: Estudio retrospectivo tipo serie de casos comparativos con niños de 1 mes a 14 años hospitalizados por shock séptico del 2018 al 2020 en una UCIP de Lima en Perú. Los pacientes fueron divididos en fallecidos y vivos según su condición al alta de la Unidad. La influencia de cada variable sobre la mortalidad fue evaluada mediante un modelo de regresión logística. RESULTADOS: Ingresaron 174 pacientes al estudio, fallecieron 51 (29.3%). Los fallecidos en comparación con los vivos fueron de mayor edad, tuvieron más casos oncológicos (31.4% vs. 14.6%; p = 0.011), presentaron con mayor frecuencia hemoglobina ≤ 9 g/dL (44% vs. 28%; p = 0.043), lactato > 2 mmol/L (70% vs. 44%; p = 0.002), plaquetas ≤ 150 (×103)/µL (77% vs. 42%; p < 0.001) y pH ≤ 7,1 (31% vs. 6%; p < 0.001). En la regresión logística ajustada los factores que se relacionaron con la mortalidad fueron tener un pH ≤ 7,1 (OR = 8.95; IC 95%: 2.52 a 31.75) y plaquetas ≤ 150 (×103)/µL (OR = 3.89; IC 95%: 1.40 a 10.84). CONCLUSIONES: Los factores relacionados con la mortalidad en pacientes hospitalizados por shock séptico fueron tener un pH ≤ 7.1 y plaquetas ≤ 150 (×103)/µL en los controles realizados al ingreso de la UCIP.

One-year survival after admission in the intensive care unit: a retrospective cohort study.

INTRODUCTION: Improving survival is the objective of intensive care units. Various factors affect long-term outcomes. The objective was to explore survival and the associated factors 1 year after admission to the intensive care unit. METHOD: This is an observational, descriptive, and analytical study in a retrospective cohort of adults admitted to an intensive care unit at a regional hospital during the first semester of 2022. Records of 218 patients from an anonymized database were analyzed. RESULTS: The average age was 61 years, and the average APACHE II score was 15 points (24% expected mortality). Survival 1 year after admission was 57.8%. Factors associated with 1-year survival in the Cox regression model were age and APACHE II. The univariate analysis showed that the cancer was significantly associated with lethality after 1 year (OR 10.55; 95%CI 1.99-55.76). CONCLUSION: One-year survival after intensive care unit decreases by 16.1%. Factors that significantly reduced survival were old age, severity, and oncologic cause at admission.

Impact of the COVID-19 pandemic on cancer mortality in Brazil.

BACKGROUND: In the first year of the COVID-19 pandemic, data projections indicated an increase in cancer mortality for the following years due to the overload of health services and the replacement of health priorities. The first studies published with data from mortality records have not confirmed these projections. However, cancer mortality is not an outcome that occurs immediately, and analyses with more extended follow-up periods are necessary. This study aims to analyze the impact of the COVID-19 pandemic on the mortality from all types and the five most common types of cancer in Brazil and investigate the relationship between the density of hospital beds and mortality from COVID-19 in cancer patients in Brazil's Intermediate Geographic Regions (RGIs). METHODS: The Brazilian Mortality Information System provided data on the deaths from trachea, bronchus, and lung, colorectal, stomach, female breast, and prostate cancer and all types of cancer, and from COVID-19 in individuals who had cancer as a contributing cause of death. Predicted rates for 2020-2022 were compared with the observed ones, through a rate ratio (RR). An association analysis, through multivariate linear regression, was carried out between mortality from COVID-19 in cancer patients, the rate of hospital beds per 100,000 inhabitants, and the Human Development Index of the 133 RGIs of Brazil. RESULTS: In 2020, 2021, and 2022, mortality from all cancers in Brazil was lower than expected, with an RR of 0.95, 0.94, and 0.95, respectively, between the observed and predicted rates. Stomach cancer showed the largest difference between observed and expected rates: RR = 0.89 in 2020 and 2021; RR = 0.88 in 2022. Mortality from COVID-19 in cancer patients, which reached its peak in 2021 (6.0/100,000), was negatively associated with the density of hospital beds in the public health system. CONCLUSIONS: The lower-than-expected cancer mortality during 2020-2022 seems to be partly explained by mortality from COVID-19 in cancer patients, which was probably underestimated in Brazil. The findings suggested a protective role of the availability of hospital care concerning deaths due to COVID-19 in this population. More extensive follow-up is needed to understand the impact of the COVID-19 pandemic on cancer mortality.

Indicators of social inequalities associated with cancer mortality in Brazilian adults: scoping review. / Indicadores de desigualdades sociais associados à mortalidade por neoplasias nos adultos brasileiros: revisão de escopo.

The objective of this study was to identify indicators of social inequalities associated with mortality from neoplasms in the Brazilian adult population. A scoping review method was used, establishing the guiding question: What is the effect of social inequalities on mortality from neoplasms in the Brazilian adult population? A total of 567 papers were identified, 22 of which were considered eligible. A variety of indicators were identified, such as the Human Development Index and the Gini Index, which primarily assessed differences in income, schooling, human development and vulnerability. A single pattern of association between the indicators and the different neoplasms was not established, nor was a single indicator capable of explaining the effect of social inequality at all levels of territorial area and by deaths from all types of neoplasms identified. It is known that mortality is influenced by social inequalities and that the study of indicators provides an opportunity to define which best explains deaths. This review highlights important gaps regarding the use of non-modifiable social indicators, analysis of small geographical areas, and limited use of multidimensional indicators.

O objetivo deste estudo foi identificar indicadores de desigualdades sociais associados à mortalidade por neoplasias na população adulta brasileira. Utilizou-se como método a revisão de escopo, estabelecendo-se a pergunta norteadora: qual o efeito das desigualdades sociais na mortalidade por neoplasias na população adulta brasileira? Foram identificados 567 trabalhos, sendo 22 considerados elegíveis. Identificou-se uma diversidade de indicadores, como o Índice de Desenvolvimento Humano e o Índice de Gini, entre outros, que avaliaram primordialmente diferenças de renda, escolarização, desenvolvimento humano e vulnerabilidade. Não foi estabelecido um único padrão de associação entre os indicadores e as diferentes neoplasias, assim como não se identificou um indicador único capaz de explicar o efeito da desigualdade social em todos os níveis de área e por óbitos por todos os tipos de neoplasias, mas identificou-se que a mortalidade é influenciada pelas desigualdades sociais e que o estudo dos indicadores proporciona definir qual melhor explica os óbitos. Essa revisão destaca importantes lacunas referentes ao uso de indicadores sociais não modificáveis, à análise de pequenas áreas e ao uso limitado de indicadores multidimensionais.

Decreased Long-Term Survival of Patients With Newly Diagnosed Cancer Discharged Home After Unplanned ICU Admission: A Prospective Observational Study.

IMPORTANCE AND OBJECTIVES: To compare the 18-month survival between patients with newly diagnosed cancer discharged home after early unplanned ICU admission and those without early unplanned ICU admission; we also evaluated the frequency and risk factors for early unplanned ICU admission. DESIGN: Observational study with prospectively collected data from September 2019 to June 2021 and 18 months follow-up. SETTING: Single dedicated cancer center in São Paulo, Brazil. PARTICIPANTS: We screened consecutive adults with suspected cancer and included those with histologically proven cancer from among 20 highly prevalent cancers. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The exposure was early unplanned ICU admission, defined as admission for medical reasons or urgent surgery during the first 6 months after cancer diagnosis. The main outcome was 18-month survival after cancer diagnosis, and the main analysis was Cox's proportional hazards model adjusted for confounders and immortal time bias. Propensity score matching was used in the sensitivity analysis. We screened 4738 consecutive adults with suspected cancer and included 3348 patients. Three hundred twelve (9.3%) had early unplanned ICU admission, which was associated with decreased 18-month survival both in the unadjusted (hazard ratio, 4.03; 95% CI, 2.89-5.62) and adjusted (hazard ratio, 1.84; 95% CI, 1.29-2.64) models. The sensitivity analysis confirmed the results because the groups were balanced after matching, and the 18-month survival of patients with early ICU admission was lower compared with patients without early ICU admission (87.0% vs. 93.9%; p = 0.01 log-rank test). Risk factors for early unplanned ICU admission were advanced age, comorbidities, worse performance status, socioeconomic deprivation, metastatic tumors, and hematologic malignancies. CONCLUSIONS: Patients with newly diagnosed cancer discharged home after early unplanned ICU admission have decreased 18-month survival compared with patients without early unplanned ICU admission.

Loneliness as a predictor of mortality in cancer patients, a cohort study / La soledad como predictor de mortalidad en pacientes con cáncer, un estudio de cohorte

Introduction. Some studies have indicated that loneliness may be associated with an increased risk of mortality in cancer patients, as it can weaken treatment response and the immune system, and promote harmful behaviors, worsening the prognosis and increasing the likelihood of death. Addressing loneliness in public health is essential to provide social support and improve outcomes in cancer patients. Objective. To obtain an estimator of the unwanted loneliness-mortality association. Materials and methods. We followed a prospective cohort of 400 patients for two years (exposure=loneliness levels; outcome=mortality; sociodemographic and clinical control variables were included). A parametric survival model (log normal) was used. Results. The cohort had a median survival of 20.2 months and a mortality rate of 3.2 deaths/100 patient-months (95% CI: 2.8 to 3.7). The survival model found the following time ratios (TR): moderate level/low level: TR=0.55; 95% CI: 0.39 to 0.77; moderately high level/low level: TR=0.62; 95% CI: 0.41 to 0.93; high level/low level: TR=1.17; 95% CI: 0.31 to 4.42. Conclusion. Compared to patients with low levels of loneliness, patients with moderate or moderately high levels reach death more quickly (statistically significant TRs, adjusted for the effect of other variables in the model); this highlights the need for interventions to mitigate loneliness and promote social support in patients having cancer.

Introducción. Algunos estudios han señalado que la soledad podría estar relacionada con un aumento en el riesgo de mortalidad en pacientes con cáncer ya que puede debilitar la respuesta al tratamiento y del sistema inmunológico y promover comportamientos perjudiciales, lo que puede empeorar el pronóstico y aumentar la probabilidad de muerte en estos pacientes. El abordar la soledad en la salud pública es esencial para brindar apoyo social y mejorar los resultados en los pacientes con cáncer. Objetivo. Obtener un estimador de la asociación soledad no deseada - mortalidad en pacientes con cáncer. Materiales y métodos. Se le hizo el seguimiento durante dos años a una cohorte prospectiva de 400 pacientes (exposición=niveles de soledad; desenlace=tiempo hasta la muerte). Se incluyeron variables de control sociodemográficas y clínicas. Se utilizó un modelo de supervivencia paramétrico (log normal). Resultados. En la cohorte se encontró una mediana de supervivencia de 20,2 meses y una tasa de mortalidad de 3,2 muertes por 100 pacientes-mes (IC95 %: 2,8 a 3,7). En el modelo de supervivencia se encontraron las siguientes razones de tiempo (RT): nivel moderado-nivel bajo: RT=0,55; IC95 %: 0,39 a 0,77; nivel moderadamente alto-nivel bajo: RT=0,62; IC95 %: 0.41 a 0.93; nivel alto-nivel bajo: RT=1,17; IC95 %: 0,31 a 4,42. Conclusión. En comparación con los pacientes con niveles bajos de soledad, los pacientes con niveles moderados o moderadamente altos llegan más rápidamente a la muerte (RT estadísticamente significativas, habiendo ajustado por el efecto de las demás variables del modelo). Esto sugiere la utilidad de las intervenciones para mitigar la soledad y promover el apoyo social en los pacientes con cáncer.

Unplanned Hospital Admissions in Patients With Solid Tumors in Brazil: Causes and Progressive Disease's Impact on Outcomes.

PURPOSE: Most patients with cancer will be hospitalized throughout the disease course. However, most evidence on the causes and outcomes of these hospitalizations comes from administrative data or small retrospective studies from high-income countries. METHODS: This study is a retrospective cohort of patients with solid tumors hospitalized from February 1, 2021, to December 31, 2021, in a tertiary cancer center in São Paulo, Brazil. We collected data on cancer diagnosis, symptoms at admission, hospitalization diagnosis, and survival clinical outcomes during in-hospital stay (in-hospital mortality) and after discharge (readmission rates and overall survival [OS]). Progressive disease (PD) diagnosis during admission was retrieved from manual chart review if explicitly stated by the attending physician. We modeled in-hospital mortality and postdischarge OS with logistic regression and Cox proportional hazards models, respectively. RESULTS: A total of 3,726 unique unplanned admissions were identified. The most common symptoms at admission were pain (40.6%), nausea (16.8%), and dyspnea (16.1%). PD (34.0%), infection (31.1%), and cancer pain (13.4%) were the most frequent reasons for admission. The in-hospital mortality rate was 18.9%. Patients with PD had a high in-hospital mortality rate across all tumor groups and higher odds of in-hospital death (odds ratio, 3.5 [95% CI, 3.0 to 4.2]). The 7-, 30-, and 90-day readmission rates were 11.9%, 33.5%, and 54%, respectively. The postdischarge median OS (mOS) was 12.6 months (95% CI, 11.6 to 13.7). Poorer postdischarge survival was observed among patients with PD (mOS, 5 months v 18 months; P < .001; hazard ratio, 2.4 [95% CI, 2.1 to 2.6]). CONCLUSION: PD is a common diagnosis during unplanned hospitalizations and is associated with higher in-hospital mortality rates and poorer OS after discharge. Oncologists should be aware of the prognostic implications of PD during admission and align goals of care with their patients.

[Estimation of cancer incidence in Brazil and its regions in 2018: methodological aspects]. / Estimativa de incidência de câncer no Brasil e regiões em 2018: aspectos metodológicos.

The aim of this study was to develop a methodology for estimating cancer incidence in Brazil and its regions. Using data from population-based cancer registries (RCBP, acronym in Portuguese) and the Brazilian Mortality Information System (SIM, acronym in Portuguese), annual incidence/mortality (I/M) ratios were calculated by type of cancer, age group and sex in each RCBP. Poisson longitudinal multilevel models were applied to estimate the I/M ratios by region in 2018. The estimate of new cancer cases in 2018 was calculated by applying the estimated I/M ratios to the number of SIM-corrected deaths that occurred that year. North and Northeast concentrated the lowest I/M ratios. Pancreatic, lung, liver and esophageal cancers had the lowest I/M ratios, whereas the highest were estimated for thyroid, testicular, prostate and female breast cancers. For 2018, 506,462 new cancer cases were estimated in Brazil. Female breast and prostate were the two main types of cancer in all regions. In the North and Northeast, cervical and stomach cancers stood out. Differences in the I/M ratios between regions were observed and may be related to socioeconomic development and access to health services.

O objetivo deste estudo foi desenvolver metodologia para estimar a incidência de câncer no Brasil e regiões. A partir de dados dos registros de câncer de base populacional (RCBP) e do Sistema de Informações sobre Mortalidade (SIM) foram calculadas razões de incidência e mortalidade (I/M) anuais, tipo de câncer, faixa etária e sexo em cada RCBP. Para estimar as razões I/M por região em 2018, foram aplicados modelos multiníveis longitudinais de Poisson. A estimativa de casos novos de câncer, em 2018, foi calculada aplicando-se as razões I/M estimadas ao número de óbitos corrigidos do SIM ocorridos naquele ano. Norte e Nordeste concentraram as menores razões I/M. Os cânceres de pâncreas, pulmão, fígado e esôfago tiveram as menores razões I/M, enquanto as maiores razões I/M foram estimadas para câncer de tireoide, testículo, próstata e mama feminina. Para 2018, foram estimados 506.462 casos novos de câncer no Brasil. Mama feminina e próstata foram os dois principais tipos de câncer em todas as regiões. No Norte e no Nordeste, destacaram-se os cânceres do colo do útero e de estômago. Diferenças nas razões I/M entre as regiões foram observadas e podem estar relacionadas ao desenvolvimento socioeconômico e ao acesso a serviços de saúde.

El objetivo de este estudio fue desarrollar una metodología para estimar la incidencia de cáncer en Brasil y sus regiones. A partir de datos de los registros de cáncer de base poblacional (RCBP) y el Sistema de Informaciones de Mortalidad (SIM), se calcularon las tasas anuales de incidencia y mortalidad (I/M), tipo de cáncer, grupo de edad y sexo en cada RCBP. Para estimar las tasas de I/M por región en 2018, se aplicaron modelos multinivel longitudinales de Poisson. Los nuevos casos de cáncer en 2018 se estimaron mediante la aplicación de las tasas I/M que se esperan para el número de muertes corregidas de SIM que habían ocurrido ese año. Las regiones Norte y Nordeste concentraron las más bajas tasas de I/M. Los cánceres de páncreas, pulmón, hígado y esófago tuvieron las más bajas tasas de I/M, mientras que las más altas tasas de I/M se estimaron para los cánceres de tiroides, testículos, próstata y mama femenina. Para 2018, se estimaron 506.462 nuevos casos de cáncer en Brasil. La mama femenina y la próstata representaron técnicas de estimación y configuraron ser los tipos principales de cáncer en todas las regiones. En el Norte y el Nordeste se destacaron los cánceres de cuello uterino y estómago. Se observaron diferencias en las tasas de I/M entre regiones, las cuales pueden estar relacionadas con el desarrollo socioeconómico y el acceso a los servicios de salud.

Comparing the clinical characteristics and outcomes of septic shock children with and without malignancies: a retrospective cohort study.

OBJECTIVE: There is an amelioration in mortality rates of septic shock patients with malignancies over time, but it remains uncertain in children. Therefore, the authors endeavored to compare the clinical characteristics, treatment needs, and outcomes of septic shock children with or without malignancies. METHODS: The authors retrospectively analyzed the data of children admitted to the PICU due to septic shock from January 2015 to December 2022 in a tertiary pediatric hospital. The main outcome was in-hospital mortality. RESULTS: A total of 508 patients were enrolled. The proportion of Gram-negative bacteria and fungal infections in children with malignancies was significantly higher than those without malignancies. Septic shock children with malignancies had a longer length of stay (LOS) in the hospital (21 vs. 11 days, p<0.001). However, there were no statistically significant differences in the LOS of PICU (5 vs. 5 days, p = 0.591), in-hospital mortality (43.0 % vs. 49.4 %, p = 0.276), and 28-day mortality (49.2 % vs. 44.7 %, p = 0.452). The 28-day survival analysis (p = 0.314) also showed no significant differences. CONCLUSION: Although there are significant differences in the bacterial spectrum of infections, the septic shock children with or without malignancies showed a similar mortality rate. The septic shock children with malignancies had longer LOS of the hospital.

Prognostic risk stratification using C-reactive protein, albumin, and associated inflammatory biomarkers in patients with advanced cancer in palliative care.

PURPOSE: To evaluate the prognostic value of C-reactive protein (CRP), albumin, CRP/albumin ratio (CAR), and modified Glasgow Prognostic Score (mGPS) at different thresholds in patients with advanced cancer in palliative care. METHODS: Prospective cohort study with patients evaluated at a palliative care unit in Brazil between July 2016 and March 2020. We included patients ≥ 20 years old, both sexes, able to provide the necessary information or accompanied by someone able to do so, and Karnofsky Performance Status ≥ 30 %. The exclusion criteria were the absence of laboratory data and previous diagnosis of autoimmune and infectious diseases. The thresholds analyzed were: CRP < 5 vs. 5-10 vs. > 10 mg/L, albumin < 2.4 vs. 2.4-2.9 vs. 3.0-3.5 vs. > 3.5 g/dL; CAR <1.2 vs. 1.2-2.0 vs. > 2.0, and mGPS equal to 0 vs. 1 vs. 2. Kaplan-Meier curves and Cox regression models (with hazard ratios [HR] and 95% confidence interval [CI]) were used to evaluate prognostic value, and the concordance statistic (C-statistic) was used to evaluate the predictive accuracy of these thresholds to predict death within 90 days. RESULTS: A total of 1,877 patients were included. Median overall survival was 51 (19;124) days and decreased in line with the deterioration of the inflammatory biomarkers. According to the Cox regression models, HR increased as the thresholds worsened (CRP: 1.74 [95% CI, 1.50-2.02] to 2.30 [95% CI, 2.00-2.64]; albumin: 1.77 [95% CI, 1.52-2.07] to 2.60 [95% CI, 2.15-3.14]; CAR: 1.47 [95% CI, 1.21-1.77] to 2.35 [95% CI, 2.05-2.69]; mGPS: 1.78 [95% CI, 1.40-2.23] to 1.89 [95% CI, 1.65-2.15]). All the inflammatory biomarkers evaluated showed discriminatory accuracy for predicting death (C-statistic >0.70), with CAR as the best parameter (C-statistic: 0.80). CONCLUSION: Our results suggest that CRP, albumin, CAR, and mGPS can be used as clinically meaningful biomarkers to stratify patients with advanced cancer in palliative care according to the severity of these indicators.

GLIM criteria validation and reliability in critically ill patients with cancer: A prospective study.

BACKGROUND: The present study aims to assess the interrater reliability of the Global Leadership Initiative on Malnutrition (GLIM) criteria, a framework to provide a consensus diagnosis of malnutrition. We also aimed to investigate its concurrent and predictive validity in the context of patients with cancer admitted to the intensive care unit (ICU). METHODS: Individuals aged ≥19 years with cancer who were admitted to the ICU within 48 h of their initial hospital admission were included. Nutrition status was assessed with the Nutritional Risk Screening 2002, the Subjective Global Assessment (SGA), and the GLIM criteria. Interrater reliability was assessed by the kappa test (>0.80). The SGA served as the established benchmark for assessing concurrent validity. To evaluate predictive validity, the occurrence of mortality within 30 days was the outcome, and Cox regression models were applied. RESULTS: A total of 212 patients were included: 66.9% were at nutrition risk, and 45.8% were malnourished according to the SGA. According to the GLIM criteria, 68.4% and 66% were identified as malnourished by evaluators 1 and 2, respectively (κ = 0.947; P < 0.001). The GLIM combination incorporating weight loss and the presence of inflammation exhibited sensitivity (82.4%) and specificity (92%). In the multivariate Cox regression models, most GLIM combinations emerged as independent predictors of complications. CONCLUSION: The GLIM criteria demonstrated satisfactory interrater reliability, and the combination involving weight loss and the presence of inflammation exhibited noteworthy sensitivity and specificity. Most GLIM combinations emerged as independent predictors of 30-day mortality.

Social gradient and rural-urban disparities in cancer mortality in Costa Rica.

INTRODUCTION: Data on social inequalities in cancer mortality are sparse, especially in low- and middle-income countries. We aimed to analyze the socioeconomic inequalities in cancer mortality in Costa Rica between 2010 and 2018. METHODS: We linked 9-years of data from the National Electoral Rolls, National Birth Index and National Death Index to classify deaths due to cancer and socioeconomic characteristics of the district of residence, as measured by levels of urbanicity and wealth. We analyzed the fifteen most frequent cancer sites in Costa Rica among the 2.7 million inhabitants aged 20 years and older. We used a parametric survival model based on a Gompertz distribution. RESULTS: Compared to urban areas, mixed and rural area residents had lower mortality from pancreas, lung, breast, prostate, kidney, and bladder cancers, and higher mortality from stomach cancer. Mortality from stomach, lung and cervical cancer was higher, and mortality from colorectal cancer, non-Hodgkin lymphoma and leukemia was lower in the most disadvantaged districts, compared to the wealthiest ones. CONCLUSION: We observed marked disparities in cancer mortality in Costa Rica in particular from infection- and lifestyle- related cancers. There are important opportunities to reduce disparities in cancer mortality by targeting cancer prevention, early detection and opportune treatment, mainly in urban and disadvantaged districts.

The death risk of pediatric patients with cancer-related sepsis requiring continuous renal replacement therapy: a retrospective cohort study.

OBJECTIVE: To assess the outcome of patients with cancer-related sepsis requiring continuous renal replacement therapy (CRRT) in a single-center pediatric intensive care unit (PICU). METHOD: Children with sepsis who necessitate CRRT from January 2017 to December 2021 were enrolled. The patients with leukemia/lymphoma or solid tumors were defined as underlying cancer. Multivariate logistic regression analysis was performed to identify the death risk factors in patients with cancer-related sepsis. RESULTS: A total of 146 patients were qualified for inclusion. Forty-six (31.5%) patients with cancer-related sepsis and 100 (68.5%) non-cancer-related sepsis. The overall PICU mortality was 28.1% (41/146), and mortality was significantly higher in cancer-related sepsis patients compared with non-cancer patients (41.3% vs. 22.0%, p = 0.016). Need mechanical ventilation, p-SOFA, acute liver failure, higher fluid overload at CRRT initiation, hypoalbuminemia, and high inotropic support were associated with PICU mortality in cancer-related sepsis patients. Moreover, levels of IL-6, total bilirubin, creatinine, blood urea nitrogen, and international normalized ratio were significantly higher in non-survivors than survivors. In multivariate logistic regression analysis, pediatric sequential organ failure assessment (p-SOFA) score (OR:1.805 [95%CI: 1.047-3.113]) and serum albumin level (OR: 0.758 [95%CI: 0.581 -0.988]) were death risk factors in cancer-related sepsis receiving CRRT, and the AUC of combined index of p-SOFA and albumin was 0.852 (95% CI: 0.730-0.974). CONCLUSION: The overall PICU mortality is high in cancer-related sepsis necessitating CRRT. Higher p-SOFA and lower albumin were independent risk factors for PICU mortality.

Cancer mortality risk from short-term PM2.5 exposure and temporal variations in Brazil.

Although some studies have found that short-term PM2.5 exposure is associated with lung cancer deaths, its impact on other cancer sites is unclear. To answer this research question, this time-stratified case-crossover study used individual cancer death data between January 1, 2000, and December 31, 2019, extracted from the Brazilian mortality information system to quantify the associations between short-term PM2.5 exposure and cancer mortality from 25 common cancer sites. Daily PM2.5 concentration was aggregated at the municipality level as the key exposure. The study included a total of 34,516,120 individual death records, with the national daily mean PM2.5 exposure 15.3 (SD 4.3) µg/m3. For every 10-µg/m3 increase in three-day average PM2.5 exposure, the odds ratio (OR) for all-cancer mortality was 1.04 (95% CI 1.03-1.04). Apart from all-cancer deaths, PM2.5 exposure may impact cancers of oesophagus (1.04, 1.00-1.08), stomach (1.05, 1.02-1.08), colon-rectum (1.04, 1.01-1.06), lung (1.04, 1.02-1.06), breast (1.03, 1.00-1.06), prostate (1.07, 1.04-1.10), and leukaemia (1.05, 1.01-1.09). During the study period, acute PM2.5 exposure contributed to an estimated 1,917,994 cancer deaths, ranging from 0 to 6,054 cases in each municipality. Though there has been a consistent downward trend in PM2.5-related all-cancer mortality risks from 2000 to 2019, the impact remains significant, indicating the continued importance of cancer patients avoiding PM2.5 exposure. This nationwide study revealed a notable association between acute PM2.5 exposure and heightened overall and site-specific cancer mortality for the first time to our best knowledge. The findings suggest the importance of considering strategies to minimize such exposure in cancer care guidelines. ENVIRONMENTAL IMPLICATION: The 20-year analysis of nationwide death records in Brazil revealed that heightened short-term exposure to PM2.5 is associated with increased cancer mortality at various sites, although this association has gradually decreased over time. Despite the declining impact, the research highlights the persistent adverse effects of PM2.5 on cancer mortality, emphasizing the importance of continued research and preventive measures to address the ongoing public health challenges posed by air pollution.

Usefulness of the qSOFA score for predicting hospital mortality in cancer patients.

BACKGROUND: The quick Sequential Sepsis-related Organ Failure Assessment (qSOFA) is a score that has been proposed to quickly identify patients at higher risk of death. OBJECTIVE: To describe the usefulness of the qSOFA score to predict in-hospital mortality in cancer patients. MATERIAL AND METHODS: Cross-sectional study carried out between January 2021 and December 2022. Hospital mortality was the dependent variable. The area under the ROC curve (AUC) was calculated to determine the discriminative ability of qSOFA to predict in-hospital mortality. RESULTS: A total of 587 cancer patients were included. A qSOFA score higher than 1 obtained a sensitivity of 57.2%, specificity of 78.5%, a positive predictive value of 55.4% and negative predictive value of 79.7%. The AUC of qSOFA for predicting in-hospital mortality was 0.70. In-hospital mortality of patients with qSOFA scores of 2 and 3 points was 52.7 and 64.4%, respectively. In-hospital mortality was 31.9% (187/587). CONCLUSION: qSOFA showed acceptable discriminative ability for predicting in-hospital mortality in cancer patients.

ANTECEDENTES: El quick Sequential Sepsis-related Organ Failure Assessment (qSOFA) es una puntuación propuesta para identificar de forma rápida a pacientes con mayor probabilidad de morir. OBJETIVO: Describir la utilidad de la puntuación qSOFA para predecir mortalidad hospitalaria en pacientes con cáncer. MATERIAL Y MÉTODOS: Estudio transversal realizado entre enero de 2021 y diciembre de 2022. La mortalidad hospitalaria fue la variable dependiente. Se calculó el área bajo la curva ROC (ABC) para determinar la capacidad discriminativa de qSOFA para predecir mortalidad hospitalaria. RESULTADOS: Se incluyeron 587 pacientes con cáncer. La puntuación qSOFA < 1 obtuvo una sensibilidad de 57.2 %, una especificidad de 78.5 %, un valor predictivo positivo de 55.4 % y un valor predictivo negativo de 79.7 %. El ABC de qSOFA para predecir mortalidad hospitalaria fue de 0.70. La mortalidad hospitalaria de los pacientes con qSOFA de 2 y 3 puntos fue de 52.7 y 64.4 %, respectivamente. La mortalidad hospitalaria fue de 31.9 % (187/587). CONCLUSIÓN: qSOFA mostró capacidad discriminativa aceptable para predecir mortalidad hospitalaria en pacientes con cáncer.

Strength-to-muscle radiodensity: A potential new index for muscle quality.

BACKGROUND & AIMS: Although it is widely recognized that muscle quality significantly influences adverse outcomes in patients with cancer, the precise definition of muscle quality remains elusive. The muscle quality index (MQI), also known as muscle-specific strength, is a relatively recent functional concept of muscle quality. It is obtained through the ratio of muscle strength to muscle mass, but its predictive value in patients with cancer remains unknown. In this study, we explored the prognostic significance of MQI in patients with cancer. Furthermore, we introduce and assess the prognostic potential of a novel muscle quality metric: the strength-to-muscle-radiodensity index (SMRi). METHODS: A secondary analysis was conducted on a prospective cohort study. CT scans were opportunistically used to assess body composition parameters, including skeletal muscle mass (SM in cm2) and muscle radiodensity (SMD in HU) at the third lumbar vertebra (L3). Handgrip strength (HGS) was measured. MQICT was calculated using the ratio of HGS to SM (cm2). SMRi was calculated as the ratio of HGS to SMD (HU). For analysis purposes, low MQICT and SMRi were defined using two approaches: statistical cutoffs associated with survival, and median-based distribution data. RESULTS: A total of 250 patients were included (52.8% females, 52% adults, 20-90 years). Gastrointestinal tumors and stage III-IV were the most frequent diagnosis and stages. SMRi and MQICT were strongly positively correlated (ρ = 0.71 P < 0.001). Individual components of MQICT and SMRi were also positively correlated. Patients with both low MQICT and SMRi had shorter survival (log-rank P = 0.023 and P = 0.003, respectively). When applying median distribution cutoffs, SMRi emerged as the most accurate predictor of mortality (HR adjusted 3.18, 95% CI 1.50 to 6.75, C-index: 0.71), when compared to MQICT (HR adjusted 1.49, 95% CI 0.77 to 2.87, C-index: 0.68). CONCLUSION: This study introduces the concept and potential prognostic significance of the SMRi. The physiological and clinical implications of this new index warrant further investigation across a spectrum of diseases, including cancer.

Exploring the role of body mass index-adjusted calf circumference within the SARC-CalF screening tool among older patients with cancer.

OBJECTIVES: This study aimed to assess and compare the frequency of positive scores using unadjusted SARC-CalF with the scores derived from SARC-CalF after adjusting calf circumference (CC) for body mass index (BMI). The secondary aim was to assess the prognostic value of SARC-CalF after BMI adjustment, for length of hospital stay (LOS) and mortality. DESIGN, SETTING, AND PARTICIPANTS: This secondary analysis of a prospective cohort study, included both outpatients and inpatients of an oncology unit hospital in Brazil. MEASUREMENTS: BMI and CC were measured. Patients with excess weight had their CC adjusted for BMI by subtracting 3 cm, 7 cm, and 12 cm from the unadjusted CC values for respective BMI categories. SARC-CalF was used to screen for sarcopenia. Scores ≥11 were indicative of sarcopenia, considering both unadjusted and BMI-adjusted CC values. Clinical outcomes included prolonged LOS and both short- and long-term mortality. RESULTS: Our study included 206 subjects, with a median age of 69 years, and the majority were males (52.1%). The prevalence of low CC increased from 65% to 84% after BMI adjustment. Positive unadjusted SARC-CalF scores (≥11) were observed in 51% of the population and this prevalence increased to 65% using BMI-adjusted SARC-CalF criteria (≥11). Higher scores on BMI-adjusted SARC-CalF but not unadjusted SARC-CalF were independently associated with prolonged LOS [adjusted HR: 1.26 (1.03-1.53)], and 6-month mortality [adjusted HR: 1.42 (1.07-1.87)]. Both unadjusted and BMI-adjusted SARC-CalF were independently associated with 12-month mortality. CONCLUSION: BMI-adjusted SARC-CalF may be a promising strategy to enhance the detection of older patients with cancer and excess weight at risk of sarcopenia, and it may serve a dual role as a prognostic tool, as it was independently associated with prolonged LOS and mortality.