Effect of urbanization and water quality on microplastic distribution in Conceição Lagoon watershed, Brazil.

Urbanization in watersheds leads to the introduction of sources of microplastics and other pollutants in water bodies. However, the effect of urbanization on microplastic pollution and the relationship between microplastics and water quality are not well understood. We assessed the distribution of microplastics in tributaries urbanized, non-urbanized and in the receiving lagoon body of Conceição Lagoon watershed. The results show that urbanization significantly affects water quality but does not differentiate tributaries in terms of microplastic concentrations. Microplastic concentrations were lower in the receiving lagoon body compared with the tributaries, highlighting their importance in microplastic pollution in the studied lagoon. Microplastic concentration was correlated with low N:P ratios in the lagoon and associated with high levels of total phosphorus, which indicate the discharge of effluents. The correlations between microplastic concentration, water temperature, and dissolved oxygen in the lagoon were based on the temporal variations of these variables. Precipitation and wind velocity had influence on microplastic distribution in the watershed. Our findings underscore the importance of evaluating water quality parameters and meteorological variables to comprehend the microplastic distribution at small watersheds.

Impact of Synchronous versus Metachronous Metastasis on Outcomes in Patients with Metastatic Renal Cell Carcinoma Treated with First-line Immune Checkpoint Inhibitor-based Combinations.

BACKGROUND AND OBJECTIVE: The impact of time of metastasis onset with respect toprimary renal cell carcinoma (RCC) diagnosis on survival outcomes is not well characterized in the era of immune checkpoint inhibitor (ICI)-based combinations. Herein, we assessed differences in clinical outcomes between synchronous and metachronous metastatic RCC (mRCC). METHODS: Data for patients with mRCC treated with first-line ICI-based combination therapies between 2014 and 2023 were retrospectively collected. Patients were categorized as having synchronous metastasis if present within 3 mo of RCC diagnosis; metachronous metastasis was defined as metastasis >3 mo after primary diagnosis. Time to treatment failure (TTF), overall survival (OS), and the disease control rate (DCR) were assessed. KEY FINDINGS AND LIMITATIONS: Our analysis included 223 eligible patients (126 synchronous and 97 metachronous). Median TTF did not significantly differ between the synchronous and metachronous groups (9 vs 19.8 mo; p = 0.063). Median OS was significantly shorter in the synchronous group (28.0 vs 50.9 mo; p = 0.001). Similarly, patients with synchronous metachronous metastasis (58.7% vs. 78.4%; p = 0.002). On multivariable analyses, synchronous metastasis remained independently associated with worse OS and DCR. CONCLUSIONS AND CLINICAL IMPLICATIONS: In this hypothesis-generating study, patients with mRCC with synchronous metastasis who were treated with first-line ICI-based combinations have a poorer OS and worse DCR than those with metachronous mRCC. If these results are externally validated, time to metastasis could be included in prognostic models for mRCC. PATIENT SUMMARY: Our study demonstrates that patients treated with current first-line immunotherapies, who present with metastasis at the initial diagnosis of kidney cancer have worse overall survival compared to those who develop metastasis later. These results can help physicians and patients understand life expectancy.

Entre science et engagement : les défis de la recherche communautaire au sein du réseau Coalition PLUS.

Community-based research, that is, the meaningful involvement of affected populations in the production of scientific knowledge that concerns them, is a political struggle and an ethical necessity. Coalition PLUS, an international network of organizations (most of them NGOs) fighting against HIV and hepatitis, created a community-based research laboratory (CBRL) composed of people from more than sixteen countries and various disciplinary fields. The objectives of the CBLR are to build research capacity, ensure collaboration with local and international academic research centers, and develop international research projects. The CBRL acts as a bridge between different partners, reconciling sometimes divergent interests, and must provide mediation and support to promote dialogue, transparency, and a relationship of trust between the communities and academic researchers. However, the need for scientific legitimacy obliges us to continuously seek a balance between responding to the needs of the field and using rigorous scientific methods, while optimizing and prioritizing existing resources. The permanent quest for this balance has led the CBRL to reorganize its mode of operation to optimize existing synergies with academic research laboratories, with a view to asserting its scientific legitimacy and continuing to contribute to social transformation through community-based research that is both innovative and of high quality. This paper provides a critical reflection on the issues, challenges, practices, and solutions of community-based research within the Coalition PLUS network.

Determinants of HIV Testing Among Migrant Men Who Have Sex With Men from Sub-Saharan Africa and Other Regions Residing in 10 European Countries.

Migrant men who have sex with men (mMSM) from sub-Saharan Africa (SSA) and other regions outside Europe are highly vulnerable to HIV. However, research on the determinants of HIV testing among mMSM from SSA, and how these differ across the categories of mMSM living in Europe, is limited. Using data from the European MSM Internet Survey (EMIS-2017), we assessed HIV testing prevalence and recency in mMSM from SSA and other mMSM residing in ten European countries, as well as the determinants of HIV testing across different mMSM categories with logistic regression analyses. Ever-testing for HIV was slightly higher in mMSM from SSA (83%) compared to other mMSM categories (75-80%), except for mMSM from Latin America and Caribbean region (84%). Overall, 20% of mMSM had never tested. In multivariable analysis, higher age (adjusted odds ratio [AOR] 1.05, 95% confidence interval [CI] 1.01-1.10), higher HIV knowledge (AOR 1.45, 95%-CI 1.11-1.90), and residence in smaller settlements (AOR 0.45, 95%-CI 0.21-0.96) were significantly associated with ever testing for HIV in mMSM from SSA. Comparing mMSM from SSA to mMSM from other regions, we found varying significant similarities (higher age, residence in smaller settlements and HIV knowledge) and differences (lower educational attainment, not identifying as gay, being a student, and limited disclosure of homosexual attraction) in the determinants of ever-testing for HIV. Community-specific interventions addressing identified sociodemographic and behavioral determinants to increase HIV testing uptake in the different mMSM categories and better data for further research are warranted.

When awareness is not a barrier to PrEP uptake among men who have sex with men who are eligible for PrEP in France.

Despite PrEP being available and free of charge in France, a gap remains between the estimated number of men who have sex with men (MSM) with high-risk exposure to HIV and the number of MSM PrEP users. The objective of this study is to identify factors associated with non-intention to use PrEP among PrEP-eligible and PrEP-aware MSM in France, "non-intenders".European MSM Internet Survey (EMIS)-2017 was a cross-sectional survey conducted among MSM concerning their HIV prevention needs. Logistic regression models were used to identify factors associated with "non-intenders".Compared to PrEP users, factors associated with non-intention to use PrEP were: age (aOR[95%CI] = 3.80[2.21;6.53]); not being vaccinated against hepatitis B (2.20[1.45;3.34]); self-efficacy (1.84[1.29;2.60]); lower knowledge about on-demand PrEP (11.48[7.37;17.87]) and daily PrEP (2.58[1.27;5.25]); not having a PrEP discussion at a hospital (12.39[8.90;17.27]) or at a community service/drop-in (4.93[3.48;6.97]); living in a department with few PrEP access points (1.70[1.10;2.63]).On-demand PrEP may meet the prevention needs of "non-intenders" who have lower HIV risk perception. Increasing communication from health providers and community health workers to all MSM is needed.

Men Who Have Sex with Both Men and Women in West Africa: Factors Associated with a High Behavioral Risk of Acquiring HIV from Male Partners and Transmission to Women (CohMSM ANRS 12324-Expertise France).

HIV is highly prevalent in men who have sex with men (MSM) in West Africa. Many MSM in the region also have sex with women (MSMW). Accordingly, they are a potential bridge subpopulation for HIV transmission to women. We aimed to evaluate the proportions and characteristics of West African MSMW at high behavioral risk of acquiring HIV from male partners and transmitting it to female partners (HBRMF). The cohort ANRS-12324 CohMSM Study included 630 HIV-negative MSM in Burkina Faso, Cote d'Ivoire, Mali, and Togo. Among MSMW (i.e., with ≥ 1 female partner) in the cohort, HBRMF was identified using trajectory models based on seven at-risk sexual practices with male and female partners, including inconsistent condom use, multiple partnerships, and receptive same-sex anal intercourse. To assess the relevance of using trajectory models, we compared the proportions of participants who seroconverted during the cohort follow-up among those at HBRMF and those not at HBRMF. Factors associated with HBRMF were identified using a generalized estimation equation logistic regression model accounting for longitudinal data. Approximately half (47%) of the 304 MSMW (22% of all CohMSM study participants) were at HBRMF. This group accounted for 75% of the 28 HIV seroconversions observed during follow-up (p = 0.001). HBRMF was positively associated with being aged < 25 years (aOR 95% CI 1.67 [1.23-2.27]), being sexually attracted only to men (1.97 [1.38-2.78]), feelings of loneliness (1.92 [1.38-2.65]), and homonegative violence score (1.22 [1.05-1.41]). HBRMF was negatively associated with having had both stable and casual female partners in the previous 6 months (0.34 [0.20-0.60] vs. only a stable female partner). HBRMF tended to be negatively associated with having ≥ 4 sexual intercourses with female partners in the previous four weeks (0.54 [0.27-1.06] vs. no intercourse). Establishing official relationships with women might be a strategy for young and/or stigmatized MSMW to comply with social pressure to display a heterosexual lifestyle. However, this seems to increase the risk of HIV transmission to female partners. In the present study, almost half of MSMW were at HBRMF. This result stresses the need to adapt HIV research and prevention to MSMW and their female partners.

Assessment of eligibility criteria in renal cell carcinoma trials evaluating systemic therapy.

OBJECTIVES: To characterise the restrictiveness of eligibility criteria in contemporary renal cell carcinoma (RCC) trials, using recommendations from the American Society of Clinical Oncology (ASCO)-Friends of Cancer Research (FCR) initiative. METHODS: vPhase I-III trials assessing systemic therapies in patients with RCC starting between 30 June 2012 and 30 June 2022 were identified. Eligibility criteria regarding brain metastases, prior or concurrent malignancies, hepatitis B virus (HBV) or hepatitis C virus (HCV) infection, and human immunodeficiency virus (HIV) infection were identified and stratified into three groups: exclusion, conditional inclusion, and not reported. Descriptive statistics were used to determine the frequency of eligibility criteria. Fisher's exact test or chi-square test were used to calculate their associations with certain trial characteristics. RESULTS: A total of 423 RCC trials were initially identified of which 112 (26.5%) had sufficient accessible information. Exclusion of patients with HIV infection, HBV/HCV infection, brain metastases, and prior or concurrent malignancies were reported in 74.1%, 53.6%, 33.0%, and 8.0% of trials, respectively. In the context of HIV and HBV/HCV infection, patients were largely excluded from trials evaluating immunotherapy (94.4% and 77.8%, respectively). In addition, brain metastases were excluded in trials assessing targeted therapy (36.4%), combined therapy (33.3%), and immunotherapy (22.2%). Exclusion of patients with prior or concurrent malignancies was less frequently reported, accounting for 9.1%, 8.3%, and 5.6% targeted therapy, combined therapy and immunotherapy trials, respectively. CONCLUSION: A substantial proportion of RCC trials utilise restrictive eligibility criteria, excluding patients with fairly prevalent comorbidities. Implementing the ASCO-FCR recommendations will ensure resulting data are more inclusive and aligned with patient populations in the real-world.

Impact of the COVID-19 Health Crisis on Key Populations at Higher Risk for, or Living With, HIV or Hepatitis C Virus and People Working With These Populations: Multicountry Community-Based Research Study Protocol (EPIC Program).

BACKGROUND: Information concerning the impact of the COVID-19 health crisis on populations most affected by HIV and hepatitis C virus (HCV; or key populations [KP]), and those working with these populations in community settings, is limited. Community-based organizations working in the field of HIV and viral hepatitis are well placed to identify and meet the new needs of KP owing to the health crisis. OBJECTIVE: This study aims to describe the development and implementation of an exploratory and descriptive multicountry, community-based research program, EPIC (Enquêtes Pour évaluer l'Impact de la crise sanitaire covid en milieu Communautaire), within an international network of community-based organizations involved in the response to HIV and viral hepatitis. The EPIC program aimed to study the impact of the COVID-19 health crisis on KP or people living with HIV or HCV and people working with these populations at the community level (community health workers [CHWs]) and to identify the key innovations and adaptations in HIV and HCV services. METHODS: A general protocol and study documents were developed and shared within the Coalition PLUS network. The protocol had a built-in flexibility that allowed participating organizations to adapt the study to local needs in terms of the target population and specific themes of interest. Data were collected using surveys or interviews. RESULTS: From July 2020 to May 2022, a total of 79 organizations participated in the EPIC program. Across 32 countries, 118 studies were conducted: 66 quantitative (n=12,060 among KP or people living with HIV or people living with HCV and n=811 among CHWs) and 52 qualitative (n=766 among KP or people living with HIV or people living with HCV and n=136 among CHWs). CONCLUSIONS: The results of the EPIC program will provide data to describe the impact of the health crisis on KP and CHWs and identify their emerging needs. Documentation of innovative solutions that were put into place in this context may help improve the provision of services after COVID-19 and for future health crises. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/45204.

Resilience outcomes and associated factors among workers in community-based HIV care centres during the Covid-19 pandemic: A multi-country analysis from the EPIC program.

Introduction: Community health workers (CHW) were integral in the COVID-19 response, particularly concerning services for populations vulnerable to HIV. Little is known regarding the mental health of CHW during the COVID-19 crisis. The objective of this study was to study resilience of CHW working in HIV non-governmental organizations. Methods: An anonymous online, cross-sectional questionnaire was implemented during 2021 among CHW in Benin, Colombia, Guatemala, and Spain. Three scales were used to assess mental health: the 6-item Brief-Resilience Scale, the 9-item Patient Scale Questionnaire and the 7-item Generalized-Anxiety-Disorder scale. Logistic regression models were used to identify factors associated with "low" resilience vs "normal" or "high" resilience. Results: Among 295 respondents, the median standardized resilience score was 58.33 (IQR = [50.0-75.0], n = 267), 18.52 (IQR = [7.4-33.3], n = 282) for standardized depression score and 19.05 (IQR = [4.8-33.3], n = 274) for standardized anxiety score. Standardized resilience score was negatively correlated with standardized anxiety score (rho = -0.49, p < 0.001, n = 266) and standardized depression score (rho = -0.44, p < 0.001, n = 267). Conclusions: Normal or high level of resiliency in the HIV CHW were observed during the COVID-19 crisis. Self-efficacy, through COVID-19 prevention training, was a factor associated with resilience. Health policy must place CHW at the core of the healthcare system response to Covid-19 and to future health emergencies, as they ensure continuity of care for many diseases including HIV among vulnerable populations.

Racial and ethnic differences in perceptions of germline or somatic DNA sequencing among patients with advanced prostate, urothelial, or kidney cancer.

We sought to determine racial and ethnic differences in perceptions (quality of communication, expectations, and concerns) of germline or somatic DNA sequencing (genomic profiling). Patients with prostate, urothelial, or kidney cancer were surveyed using a questionnaire that assessed previous experience, beliefs, expectations, and concerns regarding genomic profiling. Descriptive statistics and chi-square tests were used to identify factors associated with patients' perceptions of genomic profiling. A total of 150 consecutive patients were enrolled. The majority were male (74%) with a mean age of 68 years old. Most patients underwent somatic testing (54%), 24% undertook germline testing, and 21% undertook both tests. Significant differences were found across racial and/or ethnicity concerning factors that could have influenced patients' decision to pursue genomic profiling, including ability to guide the type of treatment (White: 54.1% vs. other ethnic groups: 43.9%, p = 0.04) and potential to improve treatment response (White: 10.1% vs. other ethnic groups: 22.0%, p = 0.04). Other ethnic group of patients were more concerned about learning that the cancer was less treatable or aggressive (43.8% vs. 27.7%, p = 0.01) and anxious about what would be learnt from genomic profiling (34.4% vs. 21.3, p = 0.01) as compared to White patients. Our findings reinforce the importance of developing culturally tailored education to help patients participate actively in decisions about genomic profiling.

[Unsafe practices fostering cutaneous abscesses in people who inject substances : Results from the ANRS-OUTSIDER study]. / Des pratiques à risque favorisant la survenue d'abcès cutanés chez les personnes qui injectent des substances : résultats de l'étude ANRS-OUTSIDER.

INTRODUCTION: Cutaneous abscesses are a common complication of intravenous substance use. Although these skin and soft tissue infections represent one of the main causes of emergency room visits and hospitalizations in people who inject drugs (PWID), data on their prevalence and causes are scarce. The present study was part of the larger ANRS-OUTSIDER project and aimed to study the factors associated with skin abscesses in PWID, focusing in particular on the different stages of injection. METHOD: Analyses were based on data of the 164 persons who regularly injected psychoactive substances participating in the French ANRS-OUTSIDER project. A face-to-face questionnaire collected data on sociodemographics, substance use, injection practices, and experience of skin abscesses in the previous six months. Factors associated with skin abscesses were studied using a logistic regression model. RESULTS: Of the 140 participants for whom abscess data were recorded at inclusion, 35% reported having a skin abscess in the previous six months. Factors associated with skin abscesses were: benefiting from universal health coverage (PUMA/CMU/AME) (Odd ratio (OR) = 0.28, confidence interval (CI) à 95%=0.08-0.99), finding the vein to inject by touch (OR=3.44, 95% CI=1.41-8.43) and licking the needle before injection (OR=5.16, 95% CI=1.10-24.30). CONCLUSION: Our results highlight that skin abscesses were very frequent among the complications observed in our sample of French PWID, and that certain injection practices fostered their occurrence. These data will provide stakeholders with useful information to improve prevention and harm reduction messages for PWID.

Characterization of papillary and clear cell renal cell carcinoma through imaging mass cytometry reveals distinct immunologic profiles.

Objective: To characterize and further compare the immune cell populations of the tumor microenvironment (TME) in both clear cell and papillary renal cell carcinoma (RCC) using heavy metal-labeled antibodies in a multiplexed imaging approach (imaging mass cytometry). Materials and methods: Formalin-fixed paraffin-embedded (FFPE) baseline tumor tissues from metastatic patients with clear cell renal cell carcinoma (ccRCC) and papillary renal cell carcinoma (pRCC) were retrospectively requisitioned from an institutional biorepository. Pretreated FFPE samples from 33 RCC patients (10 ccRCC, 23 pRCC) were accessioned and stained for imaging mass cytometry (IMC) analysis. Clinical characteristics were curated from an institutional RCC database. FFPE samples were prepared and stained with heavy metal-conjugated antibodies for IMC. An 11-marker panel of tumor stromal and immune markers was used to assess and quantify cellular relationships in TME compartments. To validate our time-of-flight (CyTOF) analysis, we cross-validated findings with The Cancer Genome Atlas Program (TCGA) analysis and utilized the CIBERSORTx tool to examine the abundance of main immune cell types in pRCC and ccRCC patients. Results: Patients with ccRCC had a longer median overall survival than did those with pRCC (67.7 vs 26.8 mo, respectively). Significant differences were identified in the proportion of CD4+ T cells between disease subtypes (ccRCC 14.1%, pRCC 7.0%, p<0.01). Further, the pRCC cohort had significantly more PanCK+ tumor cells than did the ccRCC cohort (24.3% vs 9.5%, respectively, p<0.01). There were no significant differences in macrophage composition (CD68+) between cohorts. Our results demonstrated a significant correlation between the CyTOF and TCGA analyses, specifically validating that ccRCC patients exhibit higher levels of CD4+ T cells (ccRCC 17.60%, pRCC 15.7%, p<0.01) and CD8+ T cells (ccRCC 17.83%, pRCC 11.15%, p<0.01). The limitation of our CyTOF analysis was the large proportion of cells that were deemed non-characterizable. Conclusions: Our findings emphasize the need to investigate the TME in distinct RCC histological subtypes. We observed a more immune infiltrative phenotype in the TME of the ccRCC cohort than in the pRCC cohort, where a tumor-rich phenotype was noted. As practical predictive biomarkers remain elusive across all subtypes of RCC, further studies are warranted to analyze the biomarker potential of such TME classifications.

Intervenciones psicológicas para mejorar la adherencia al tratamiento antirretroviral: Revisión sistemática y metaanálisis / Psychological interventions to improve adherence to antiretroviral treatment: Systematic review and meta-analysis

Resumen El VIH es una enfermedad crónica que afecta a los receptores CD4 del sistema inmunológico. El Tratamiento Antirretroviral (TARV) es vital para disminuir la carga viral, pero su éxito depende del grado de adherencia al mismo. El objetivo de este estudio fue revisar los factores asociados a la eficacia de las intervenciones psicológicas para incrementar la adherencia al TARV y agregar los hallazgos en estimaciones cuantitativas de su impacto en la adherencia. La revisión de la literatura fue realizada desde agosto de 2017 hasta abril de 2020 en PubMed, EBSCO y Springer Link, utilizando los siguientes criterios de elección de los estudios: (1) que estuvieran publicados en revistas indexadas con revisión por pares, (2) que fueran experimentales o cuasiexperimentales, (3) que emplearan técnicas para el incremento de la adherencia, (4) que estuvieran publicados en español o inglés, (5) que reportaran los estadísticos necesarios para el cálculo del tamaño de efecto. De los 15 estudios seleccionados (. total = 1669), se obtuvieron 38 tamaños del efecto. El cálculo de los tamaños de efecto individuales y global se realizó usando el programa Comprehensive Meta-Analysis (Biostat, 2011, v. 2.2.064). Todos los tamaños de efecto fueron calculados usando la diferencia estandarizada de medias y un modelo de efectos aleatorios. El tamaño de efecto global fue moderado (. = 0.56, . = 38, IC95 % = 0.39 - 0.72, . < .001), mostrando que las intervenciones fueron significativamente superiores al grupo de comparación. Debido a la alta heterogeneidad de los estudios (I. = 82.25), se analizaron 12 variables moderadoras, de las cuales 11 fueron significativas (. < .005). Los resultados del análisis de variables moderadoras indican un mayor efecto en el incremento de la adherencia al TARV en intervenciones con marcos teóricos basados en el apoyo social por pares y con metodologías adaptables a la vivencia cotidiana de la persona.

Abstract HIV is a chronic disease that affects the CD4 receptors of the immune system, so it is necessary for people with the virus to be under Antiretroviral Treatment (ART) to reduce the viral load in the body. The success of ART is related to adherence to treatment, understood as: the intake of antiretroviral drugs, follow-up of medical controls and implementation of healthy lifestyles. There are personal, social and health systems problems that prevent people from adhering to ART in an adequate way. This situation has become a public health problem because inappropriate taking of drugs often leads to drug resistance. In this way, it is necessary to implement effective psychological interventions aimed at increasing adherence to ART, to contribute to a better use of antiretrovirals and to the improvement of the quality of life of people with HIV. Accordingly, the objective was to review the factors associated with the efficacy of psychological interventions, to increase adherence to ART and to aggregate the findings in quantitative estimates of its impact on adherence. For this purpose, meta-analysis was used as a research technique that allows a quantitative analysis of results by calculating specific statistics. The literature search and review were carried out from August 2017 to May 2019 in the PubMed, Academic Search Complete (EBSCO Host) and Springer Link databases, for the identification of experimental studies that met the eligibility criteria (studies published in peer-reviewed indexed journals, experimental or quasi-experimental research, using techniques to increase adherence, published in Spanish and English and reporting the necessary statistics for effect size calculation). Of the 15 studies (total n = 1669) selected, 38 effect sizes were obtained. The calculation of the individual and global effect size was performed using the Comprehensive Meta-Analysis software (Biostat, 2011, v. 2.2.064). All the effect sizes were calculated using the standardized mean difference and a random effects model. To find out if individual effect sizes were homogeneous and therefore represent a similar measure of treatment efficacy, the Cochran Q homogeneity test was applied; based on this, the I. was calculated. Also, it was performed a publication bias calculation, the objective of which was to estimate the number of non-significant effect sizes that are required for a reduction of the global effect size to a smaller and non-significant one. The overall effect size was moderate (. = 0.56, . = 38, 95 % CI = 0.39 - 0.72, . < .001) and presented high heterogeneity (I. = 82.25). Twelve moderator variables were analyzed (year of publication, percentage of men, average age, measurement time, number of sessions / interactions, duration of sessions, total duration of intervention, economic remuneration for intervention, place where the intervention was carried out, type of intervention, intervention modality and adherence measurement), of which 11 were significant (all but intervention modality: individual vs. group therapy). The results suggest that the success of an intervention proposal to improve adherence to ART will be related to its ability to consider the components of the environment and the social situation in which the person with HIV develops, as well as their intrinsic characteristics in interaction with their context. Likewise, it is necessary to consider that the presence of adherence barriers should be treated specifically in young people and adults, as well as in men and women. Finally, it is more important to establish interventions aimed not only to increase adherence, but maintaining it, which is why it is considered necessary to propose studies aimed at maintaining adherence, as well as offering practical tools for people to make better decisions about their health.

Association Between Time-of-Day of Immune Checkpoint Blockade Administration and Outcomes in Metastatic Renal Cell Carcinoma.

BACKGROUND: Preclinical evidence demonstrating circadian rhythmicity within the immune system provides a rationale for hypothesis that immune checkpoint inhibitor (ICI) infusion time-of-day may serve as an actionable mechanism to improve outcomes. Herein, we explore the association between ICI time of infusion (TOI) and outcomes in metastatic renal cell carcinoma (mRCC). METHODS: Data from patients with mRCC who received nivolumab or nivolumab/ipilimumab, in first- or second-line were retrospectively collected. Patients who received < 20% of infusions after 16:30 were assigned to the early TOI sub-cohort, while the rest were assigned to the late TOI sub-cohort. Clinical outcomes were compared across the 2 groups. RESULTS: Among 135 patients included, 89 (65.9%) and 46 (34.1%) were assigned to early and late TOI sub-cohorts, respectively. Baseline characteristics were comparable across the 2 sub-cohorts. Objective response rate (ORR) was 36.0% with early TOI versus 29.5% with late TOI (P = .157). Median time to treatment failure (TTF) was 9.5 months in the early TOI sub-cohort versus 4.6 months in the late TOI sub-cohort with a hazard ratio (HR) of 1.405 (95% CI, 0.919-2.149; P = .11) in univariate analysis and 1.694 (95% CI, 1.064-2.698; P = .026) in multivariate analysis. Higher cut offs allocating patients into the late TOI sub-cohort yielded an incremental increase in the HR for TTF and overall survival (OS) that reached statistical significance. CONCLUSIONS: In patients with mRCC, early TOI yielded a numerical increase in ORR, TTF and OS, with the TTF difference reaching significance in multivariate analysis. Prospective randomized studies are warranted to examine the impact of chronomodulation on outcomes with ICIs in mRCC.

Real-World Outcomes of Latinx Versus Non-Latinx Patients Treated With First-Line Immunotherapy for Metastatic Renal-Cell Carcinoma.

BACKGROUND: There are limited data regarding the impact of ethnicity among patients receiving immune checkpoint inhibitors. We evaluated real-world outcomes between Latinx and non-Latinx patients with metastatic renal-cell carcinoma (mRCC) treated with first-line nivolumab/ipilimumab within 2 different healthcare settings. METHODS: We performed a retrospective analysis of patients with mRCC who received nivolumab/ipilimumab within the Los Angeles County Department of Health Services (LAC-DHS), a safety-net healthcare system, and the City of Hope Comprehensive Cancer Center (COH), a tertiary oncology center, between January 1, 2015 and December 31, 2021. Progression-free survival (PFS) and overall survival (OS) were determined using the Kaplan-Meier method and covariates were adjusted using multivariate Cox proportional hazards regression. RESULTS: Of 94 patients, 40 patients (43%) were Latinx while the remainder were non-Latinx (44 pts [46%] White, 7 pts [7%] Asian, and 3 pts [3%] Other). Fifty (53%) and 44 (47%) patients received their care at COH and LAC-DHS, respectively. Most Latinx patients (95%) were treated at LAC-DHS, and most non-Latinx patients (89%) were treated at COH. Pooled analysis by ethnicity demonstrated significantly shorter PFS in Latinx versus non-Latinx patients (10.1 vs. 25.2 months, hazard ratios [HR] 3.61, 95% CI 1.96-6.66, P ≤ .01). Multivariate analysis revealed a HR of 3.41 (95% CI 1.31-8.84; P = .01). At a median follow-up of 11.0 months, the median OS was not reached in either arm at the time of data cutoff. CONCLUSION: Latinx patients with mRCC had a shorter PFS treated with frontline nivolumab/ipilimumab compared to their non-Latinx counterparts. No difference was observed in OS although these data were immature. Larger studies are needed to further interrogate the social and economic determinants of ethnicity on clinical outcomes in mRCC.

Changes in Perception of Cure Among Patients With Genitourinary Cancers Initiating Immune Checkpoint Inhibitors: A Longitudinal Study.

BACKGROUND: We explored changes in perceptions of cure among patients with genitourinary (GU) cancers starting Immune checkpoint inhibitors (ICIs) therapy. MATERIALS AND METHODS: This longitudinal study assessed patients before starting therapy and 3-months later with a questionnaire that included patient perceptions of ICIs and the Patient-Reported Outcomes Measurement Information System (PROMIS) Anxiety scale. General linear modeling was used to investigate changes in expectation of cure over time, and chi-square tests were used to determine the association between expectation of cure and perceptions of ICIs and anxiety. RESULTS: A total of 45 patients were recruited (73% male, 84% diagnosed with renal cell carcinoma). The proportion of patients who possessed an accurate expectation of cure increased over time (55.6%-66.7%, P = .001). An accurate expectation of cure was associated with lower rates of anxiety over time. Patients with inaccurate expectation of cure reported more severe side effects and worse self-reported ECOG score at the follow-up assessment (P = .04). CONCLUSION: We found that patients with GU metastatic cancer treated with ICI therapy have increasingly accurate expectations of cure over time. Accurate expectation of cure is associated with decreased anxiety. Further research is needed to fully explore this dynamic over time and help inform interventions that can help patients develop accurate expectations.

Examining Exclusion Criteria in Advanced Prostate Cancer Clinical Trials: An Assessment of recommendations From the American Society Of Clinical Oncology and Friends of Cancer Research.

PURPOSE: Eligibility criteria illustrate the characteristics of the study population and promote the safety of participants. However, overreliance on restrictive eligibility criteria may limit the generalizability of outcomes. As a result, the American Society of Clinical Oncology (ASCO) and Friends of Cancer Research (Friends) issued statements to curtail these challenges. In this study, we aimed to assess restrictiveness in eligibility criteria across advanced prostate cancer clinical trials. MATERIALS AND METHODS: We identified all phase I, II, and III advanced prostate cancer clinical trials between June 30, 2012, and June 30, 2022, through Clinicaltrials.gov. We evaluated whether a clinical trial excluded, conditionally included, or did not report 4 common criteria: brain metastases, prior or concurrent malignancies, HIV infection, and hepatitis B virus (HBV)/hepatitis C virus (HCV) infection. Performance status (PS) criteria were recorded based on the Eastern Cooperative Oncology Group (ECOG) scale. RESULTS: Out of 699 clinical trials within our search strategy, 265 (37.9%) trials possessed all the required data and were included in our analysis. The most common excluded condition of our interest was brain metastases (60.8%), followed by HIV positivity (46.4%), HBV/HCV positivity (46.0%), and concurrent malignancies (15.5%). Additionally, 50.9% of clinical trials only included patients with ECOG PS 0 to 1. HIV and HBV/HCV infection were exclusion criteria of 22 (80.8%) and 19 (73.1%) immunotherapy trials, respectively. CONCLUSION: Patients with brain metastases, prior or concurrent malignancies, HIV infection, HBV/HCV infection, or low-functioning PS were overly restricted from participating in advanced prostate clinical trials. Advocating for broader criteria may ameliorate generalizability.

Preventive Inflammation Management with Steroids before Retreatment with Anti-VEGF after Severe Inflammation due to Brolucizumab.

PURPOSE: We report two successful cases of treatment by steroids after severe inflammation due to an intravitreal injection (IVI) of brolucizumab and their retreatment with another type of anti-vascular endothelial growth factor (VEGF), with steroid treatments to prevent severe inflammatory recurrence in patients with exudative age-related macular degeneration (AMD). CLINICAL CASES, CASE 1: An 88-year-old woman with exudative AMD in her left eye who had persistent subretinal fluid despite receiving an IVI, including ranibizumab and, subsequently, aflibercept. A switch to brolucizumab was decided. Two weeks after the third dose, she had a visual loss decreasing from 20/40 to counting fingers at 50 cm. Fundus examination revealed retinal whitening and perivenous sheathing. Fluoresceine angiography confirmed retinal arterial occlusion. Differential diagnoses were ruled out. She was treated with intravenous methylprednisolone and prednisolone eye drops. Three months after the treatment, visual acuity improved to 20/80 with no intraocular inflammation but subretinal fluid recurred. IVI of ranibizumab was rescheduled with preventive treatment by oral and local prednisolone without any inflammation recurrence. CASE 2: An 80-year-old man with exudative AMD in his right eye who had persistent subretinal fluid despite an IVI of aflibercept. Switching him to brolucizumab was decided. Two months after the third dose, he had blurred vision with no pain. Visual acuity decreased from 20/20 to 20/25. Examination showed 1+ anterior chamber cells and hyalitis. We confirmed the diagnosis of anterior uveitis with hyalitis. Differential diagnoses were ruled out. Treatment by prednisolone eye drops was initiated every 30 minutes for 1 day with a gradual decrease for 6 weeks. One week later, visual acuity improved to 20/20 with no inflammation. Three weeks later, subretinal fluid due to AMD increased. The patient was retreated by aflibercept with prednisolone eye drops, 48 hours before and after the IVI, with no recurrence of inflammation. DISCUSSION: Brolucizumab is one of the latest FDA-approved anti-VEGF agents for wet AMD. Since its wider use, few cases of severe ocular inflammation have been reported in post-marketing analysis. Because wet AMD recurrences should be expected after intraocular inflammation, insight is needed into treatment tolerance in cases that received further IVI retreatment. CONCLUSION: Our cases demonstrate that an IVI reinjection with a different anti-VEGF drug for exudative AMD recurrence can be safely reperformed. The use of local steroids could be effective in preventing recurrence of ocular inflammation after severe intraocular inflammation due to brolucizumab.