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Background: The complexity of a medication regimen is related to the multiple characteristics of the prescribed regimen and can negatively influence the health outcomes of patients. Objective: To propose cut-off points in the complexity of pharmacotherapy to distinguish between patients with low and high complexities seen in a primary health care (PHC) setting to enable prioritization of patient management. Methods: This is a cross-sectional study, which included 517 adult and elderly patients, analyzing different cut-off points to define the strata of low and high pharmacotherapy complexities based on percentiles of the population evaluated. Data collection began with the solicitation of prescriptions, followed by a questionnaire that was administered by an interviewer. The complexity of a medication regimen was estimated from the Medication Regimen Complexity Index (MRCI). High complexity pharmacotherapy scores were analyzed from patient profiles, the use of health services, and pharmacotherapy. The criteria for subject inclusion in the sample population were as follows: inhabitant of the area covered by the municipality, 18 years or older, and being prescribed at least one drug during the collection period. Exclusion criteria at the time of collection were the use of any medication whose prescription was not available. All medications were accessed through the Primary Healthcare Service (PHS). Results: The median total pharmacotherapy complexity score was 8.5. High MRCI scores were correlated with age, medications taken with in the Brazilian PHS, having at least one potential drug-related problem, receiving up to eight years of schooling, number of medications and polypharmacy (five or more medicines), number of medical conditions, number of medical appointments, and number of cardiovascular diseases and endocrine metabolic diseases. We suggest different complexity tracks according to age (e.g., adult or elderly) that consider the pharmacotherapy and population coverage characteristics as high complexity limits. For the elderly patients, the tracks were as follows: MRCI≥25.4, MRCI≥20.9, MRCI≥17.5, MRCI≥15.7, MRCI≥14.0, and MRCI≥13.0. For adult patients, the limits of high complexity were MRCI≥25.1; MRCI ≥ 23.8; MRCI≥21.0; MRCI≥17.0; MRCI≥16.5; and MRCI≥15.5. Conclusion: The medication regimen complexity is associated with the patient's illness profile and problems with the use of drugs; therefore, the proposed scores can be useful in prioritizing patients for clinical care by pharmacists and other health professionals.

Jesse Lopes da Silva,1 Giselle de Souza Carvalho,1 Lucas Zanetti de Albuquerque,1 Fabiana Resende Rodrigues,2 Priscila Valverde Fernandes,2 Daniel Kischinhevsky,1 Andreia Cristina de Melo1 1Division of Clinical Research and Technological Development, Brazilian National Cancer Institute, Rio de Janeiro, Brazil; 2Division of Pathology, Brazilian National Cancer Institute, Rio de Janeiro, BrazilCorrespondence: Jesse Lopes da Silva, Brazilian National Cancer Institute (INCA), Clinical Research Division, 37 André Cavalcanti Street, 5th Floor, Annex Building, Rio de Janeiro, 20231-050, Brazil, Tel/Fax +55 21 32076585, Email jesse.silva@inca.gov.brPurpose: This study aimed to compare the clinical behavior, clinicopathological and sociodemographic characteristics of patients with early-stage triple-negative breast cancer (TNBC) who belong to the HER2-low and HER2-zero subgroups.Patients and Methods: This study involved a thorough search in the internal database of a single Brazilian institution to identify women with TNBC who underwent neoadjuvant chemotherapy (NACT) followed by curative surgery within the period from January 2010 to December 2014. HER2 analysis through immunohistochemistry (IHC) and, if required, amplification by in situ hybridization, was conducted using core biopsy samples. The study assesses outcomes of residual cancer burden (RCB), event-free survival (EFS), and overall survival (OS).Results: A total of 170 cases were analyzed, with a mean age of 51.4 years (standard deviation, SD 11.2). The HER2 status was categorized as IHC 0, 1+, or 2+ in 80 (47.1%), 73 (42.9%), and 17 (10%) patients, respectively. No significant differences were observed in the prevalence of clinical pathological characteristics among the subgroups. The absence of significant results for clinicopathological and demographic features hindered the multivariate analysis of HER2 subgroups. Similarly, no significant differences were found in the RCB, EFS, and OS outcomes between HER2 subgroups.Conclusion: The findings of this study suggest that, in early-stage TNBC, the clinical behavior and survival outcomes of the HER2-low subgroup may not differ significantly from those of the HER2-zero subgroup.Keywords: HER2 status, HER2-low, biomarker, triple-negative breast cancer

Jesse Lopes da Silva,1 Fabiana Resende Rodrigues,2 Guilherme Gomes de Mesquita,2 Priscila Valverde Fernandes,2 Luiz Claudio Santos Thuler,1 Andreia Cristina de Melo1 1Division of Clinical Research and Technological Development, Brazilian National Cancer Institute (INCA), Rio de Janeiro, Brazil; 2Pathology Department, Brazilian National Cancer Institute, Rio de Janeiro, BrazilCorrespondence: Jesse Lopes da SilvaDivision of Clinical Research and Technological Development, Brazilian National Cancer Institute (INCA), 37 André Cavalcanti Street - 6th Floor - Annex Building, Downtown, Rio de Janeiro, RJ 20231-050, BrazilTel +55-2132076585Email jesse.silva@inca.gov.brObjective: This study aimed to investigate the influence of immunohistochemical (IHC) biomarkers in the response to neoadjuvant chemotherapy (NACT) and survival outcomes in the subset of locally advanced triple-negative breast cancer (TNBC).Materials and Methods: The epidermal growth factor receptor (EGFR), androgen receptor (AR), cytokeratins (CK5/6, CK14 and CK17), Ki67 and p53 immunohistochemistry were evaluated on 171 cases of TNBC submitted to NACT and subsequently to surgery. Intensity and percentage of the expression of these biomarkers were combined to formulate a specific score, that was correlated with prognostic features and assessed for survival outcomes.Results: Most patients had advanced clinical-stage tumors (stage III: 83.6%; cT3/T4: 85.9%; cN1-3: 71.3%). The predominant histological subtype was high-grade (67.3%) and invasive ductal carcinoma (93.6%). The residual cancer burden (RCB) 0– 1 corresponded to 28.7% of cases and low-risk lymph node ratio (LNR) represented 77.2%. High Ki67 expression only showed a significant correlation with grade 3 tumors (p = 0.0157). CK5/6 was observed in 16% (27/169), CK14 was positive in 10.1% (17/169), CK17 in 91.1% (153/168), p53 in 52.6% (70/133), EGFR in 92.9% (157/169 cases), AR in 13% (22/169) and Ki67 index was scored ≥ 40% in 57.9% (95/165). No IHC biomarker significantly impacted response or survival. Regarding the analysis of the outcomes of event-free survival (EFS) and overall survival (OS), clinical stage (p = 0.014 and p = 0.042, respectively), RCB (p < 0.0001 and p < 0.0001, respectively) and LNR (p < 0.0001 and p < 0.0001, respectively) showed significant association.Conclusion: No IHC biomarker evaluated showed a significant association with a response or survival outcomes in TNBC patients. Clinical stage, LNR and RCB stood out for strongly influencing survival.Keywords: triple-negative breast cancer, neoadjuvant chemotherapy, biomarkers, residual burden cancer, lymph node ratio

Background: Overeruption of an upper molar following loss of the opposing tooth is a common clinical finding. Rehabilitation can be difficult when the interocclusal space is reduced. Aim: To intrude an overerupted upper first molar and replace the missing lower first molar. Methods: Buccal and palatal microscrews and a transpalatal bar were placed. The palatal miniscrew loosened shortly after implantation and was not replaced. A short length of elastomeric chain from the buccal miniscrew applied 30 g of force to the overerupted molar. The elastomeric chain was replaced every four weeks. Results: Sufficient intrusion of the upper molar was obtained in 4 months. Conclusion: A single buccal microscrew and transpalatal arch can be used to intrude an overerupted upper molar. [ABSTRACT FROM AUTHOR]

Purpose: This scoping review aims to evaluate the evidence for stereotactic body radiotherapy (SBRT) boost as a potential alternative for brachytherapy (BCT) in treating cervical cancer., Material and Methods: A comprehensive literature search was conducted across multiple databases. Studies investigating SBRT boost in cervical cancer patients who were either contraindicated for or refused BCT were included. The review examined SBRT efficacy and safety., Results: Sixteen studies were included, encompassing prospective (n = 4) and retrospective cohort studies (n = 8), as well as phase I and II trials (n = 4). The most common SBRT boost dose was 25 Gray(Gy)/5 fractions (ranging from 18 to 40 Gy/3-5 fractions). Local control rates at 1-year, 3-year, and 5-year ranged from 86 % to 100 %, 78-92 %, and 81-92 %, respectively. Overall survival (OS) rates at 1-year, 3-year, and 5-year rates ranged from 49 % to 95 %, 50-77 %, and 50-69 %, respectively. Two studies reported a pathological complete response rate of 93 % and 94 % three months after the SBRT boost. Most studies reported low rates of late grade 3 or higher genitourinary (0-14 %) and gastrointestinal (0-26 %) toxicities. The overall incidence of rectovaginal fistulas ranged from 0 % to 13 %., Conclusion: This scoping review suggests SBRT boost as a promising alternative to selected cervical cancer patients who cannot receive BCT. The results indicate a high local control with acceptable toxicity profiles. However, further research is needed to define optimal SBRT boost parameters, identify patient selection criteria, and address knowledge gaps regarding long-term outcomes and cost-effectiveness., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objective: Triple-negative breast cancer (TNBC) presents a clinical challenge as an aggressive tumor, correlated with unfavorable prognosis. Tumor-infiltrating lymphocytes (TILs) have garnered interest as a potential prognostic biomarker. However, the disparity in outcomes between varying TILs rates remains inadequately explored., Methods: PubMed, Scopus, Web of Science, and Cochrane databases were searched for studies about the prognostic value of TILs in patients with TNBC receiving neoadjuvant chemotherapy. The hazard ratios (HRs) or odds ratios (ORs) were computed for binary endpoints, with 95% confidence intervals (CIs)., Results: Twenty-nine studies were included, involving a population of six thousand one hundred sixty-one (80.41%) with TNBC. The cut-off TILs value ranged from 10 to 60%, with 50% being the most related value. Compared with the low-TIL expression group, the disease-free survival (DFS) (HR 0.71; 95% CI 0.61-0.82; p < 0.00001) and overall survival (OS) (HR 0.76; 95% CI 0.63-0.90; p = 0.002) rates showed significant improvement with higher TIL infiltrations. In the subgroup analyses of the lymphocyte subtypes CD4 + and CD8 + , there was statistical significance favoring higher TILs rates in both subtypes, each associated with improved DFS (HR 0.48; 95% CI 0.33-0.71; p = 0.0002) and OS (HR 0.53; 95% CI 0.36-0.78; p = 0.001), regardless of which cell subtype was predominantly infiltrated. The complete pathological response analysis showed better rates for the higher TIL group than the control for both the TIL (OR 1.29; 95% CI 1.13-1.48; p = 0.0003) and Ki-67 (OR 2.74; 95% CI 2.01-3.73; p < 0.00001) analyses., Conclusion: Higher expressions of TILs in patients with TNBC were associated with improved significantly DFS, OS, and pCR outcomes., (© 2024. The Author(s), under exclusive licence to Federación de Sociedades Españolas de Oncología (FESEO).)

Uveal melanoma is a rare malignancy originating from extracutaneous melanocytes on the uveal layer of the eyes. The incidence varies depending on the ethnic and racial global distribution, as uveal melanoma is more frequently diagnosed in non-Hispanic White subjects when compared with Hispanic, Asian, or Black individuals. Despite all the local effective management of uveal melanoma, roughly 50% of the cases will develop distant metastases. For these cases, the historical median overall survival is around 12 months. Recently, tebentafusp became the first therapy to receive Food and Drug Administration approval following a phase 3 trial demonstrating a continued long-term benefit for overall survival among adult HLA-A*02:01-positive patients with previously untreated metastatic uveal melanoma. Since 2021, high-resolution sequence-based HLA typing has been considered the gold standard for determining HLA alleles and haplotypes for the Brazilian Bone Marrow Donor Registry (REDOME) donors. To depict the HLA-A*02:01-positivity in Brazilian individuals, the REDOME database was queried out for the donors included from 2021 to 2023 and tested for HLA in high-resolution platforms. A total of 203, 44 donors were included and the frequency of the HLA-A*02:01 was 21.01%, much lower compared to the frequency in North Americans and Europeans (around 45%). Despite tebentafusp has demonstrated promising results in the treatment of uveal melanoma, the number of patients to benefit from this new approach can strongly vary by ethnic and racial issues. New strategies for the systemic treatment of advanced uveal melanoma have to be developed and tested as this disease still represents an unmet medical need., (© The Author(s) 2024. Published by Oxford University Press.)

Tumor-associated myeloid-derived cells (MDCs) significantly impact cancer prognosis and treatment responses due to their remarkable plasticity and tumorigenic behaviors. Here, we integrate single-cell RNA-sequencing data from different cancer types, identifying 29 MDC subpopulations within the tumor microenvironment. Our analysis reveals abnormally expanded MDC subpopulations across various tumors and distinguishes cell states that have often been grouped together, such as TREM2+ and FOLR2+ subpopulations. Using deconvolution approaches, we identify five subpopulations as independent prognostic markers, including states co-expressing TREM2 and PD-1, and FOLR2 and PDL-2. Additionally, TREM2 alone does not reliably predict cancer prognosis, as other TREM2+ macrophages show varied associations with prognosis depending on local cues. Validation in independent cohorts confirms that FOLR2-expressing macrophages correlate with poor clinical outcomes in ovarian and triple-negative breast cancers. This comprehensive MDC atlas offers valuable insights and a foundation for futher analyses, advancing strategies for treating solid cancers., (© 2024. The Author(s).)

The baru ( Dipteryx alata Vog.), a fruit native to the Cerrado biome, is well-known for its almonds, which are extensively exploited and exported. Unfortunately, the remaining parts of this fruit are often discarded. This study investigates the fixed chemical constituents of the baru, including the bark, pulp, endocarp, and almonds, using the PS-MS technique in positive and negative ionization modes. Notably, this research presents the first chemical profile of baru almonds in both their raw and roasted states. The analysis identified 57 compounds reported for the first time in a baru and 24 common compounds. The majority of these compounds are classified as flavonoids. In both ionization modes, the peel exhibited a higher proportion of phenolic compounds, although the chemical compounds varied among the peel, pulp, almond, and endocarp. These findings highlight the perspective of bioeconomy and biotechnology. By staggering baru fruit production alongside extractivists, we can optimize the utilization of all parts of the fruit. Furthermore, given the knowledge of the biological properties of flavonoids and the baru composition, we recommend additional studies to analyze their potential in preventing chronic non-communicable diseases., Competing Interests: The authors declare no conflicts of interest.

Objective: Endometrial cancer (EC) treatment changed substantially with the introduction of molecular classification. Low-middle income (LMIC) countries will face barriers to including molecular classification to guide treatment. This study aims to analyse the value of p53 immunohistochemistry to delineate adjuvant treatment in FIGO stages I and II., Methods: Patients with EC treated between 2010 and 2016 were retrospectively evaluated. Patients included in this analysis must have reviewed FIGO stage I/II high-grade histologies (endometrioid grade 3, serous, clear cell, carcinosarcoma, mixed and undifferentiated). Samples were subjected to p53 immunohistochemistry. Recurrence-free and overall survival were analysed using the Kaplan-Meier method and log-rank test. Cox proportional hazards regression was performed for multivariable analysis., Results: From 2010 to 2016, 265 patients met the inclusion criteria. Patients with aberrant p53 (71.4 %) were associated with older age (59.7 % vs 77.8 % with more than 60 years), relapse (12.5 vs 29.6 %) and death (22.2 vs 46.7 %). The pattern of relapse was not different, with most being at extrapelvic sites (55.5 % vs 62.3 % for p53 wild type and aberrant, respectively). The median overall survival was not reached versus 92.2 months for p53 wild type and aberrant, respectively (p = 0.003). In multivariate analysis, chemotherapy decreased death (p = 0.014) in p53 aberrant tumours, a benefit not seen in the wild-type cohort (p = 0.22)., Conclusion: This retrospective analysis corroborates the finding of worse outcomes for p53 aberrant tumours in stage I/II EC and the benefit of more aggressive adjuvant treatment (systemic therapy and radiotherapy). Although not ideal as a sole molecular marker, p53 immunohistochemistry could complement the classical anatomopathological features and be part of the decision-making process with patients in LMIC., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Purpose: To investigate breast cancer (BC) incidence and mortality rates among specific racial groups in Brazil., Methods: BC incidence was evaluated from 2010 to 2015, using Brazilian Population-Based Cancer Registries, incorporating crude ratios and annual average percentage change (AAPC). Clinical and sociodemographic data from 2000 to 2019 were obtained from Hospital-Based Cancer Registries. Mortality data from 2000 to 2020 were sourced from the National Mortality Information System, comparing White women and Black women., Results: Across 13 Brazilian registries, 70,896 new BC cases were reported from 2010 to 2015. The median BC incidence rate was notably higher for White women (101.3 per 100,000) compared to Black women (59.7 per 100,000). In the general population, non-significant decrease in annual BC incidence was observed (AAPC = - 1.2; p = 0.474). Black women were more likely to live in underdeveloped areas, have lower education levels, live without a partner, and have higher alcohol consumption as compared to White women. A higher proportion of Black women received advanced-stage diagnoses (60.1% versus 50.6%, p < 0.001). BC-related mortality analysis showed 271,002 recorded deaths, with significant increase in BC-specific mortality rates in both racial groups. Black women displayed an AAPC of 2.3% (p < 0.001), while White women demonstrated a moderately elevated AAPC of 0.6% (p < 0.001)., Conclusion: This study underscores the need for targeted policies to address disparities in access to early detection and proper treatment, particularly for Black women in underprivileged regions, aiming to improve the survival rates of Brazilian women grappling with BC., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

By presenting a comprehensive analysis of low-grade serous carcinomas (LGSCs), a subset of epithelial ovarian cancers, this review delves into their distinct molecular characteristics, clinicopathological features and systemic therapy options, emphasizing their differences from high-grade serous carcinomas (HGSCs). Notably, LGSCs exhibit prevalent RAS/RAF/MEK/MAPK pathway activation, KRAS and BRAF mutations, and infrequent p53 mutations. While chemotherapy is commonly employed, LGSCs display lower responsiveness compared to HGSCs. Hormone therapy, particularly endocrine maintenance therapy, is explored due to the higher estrogen receptor expression. Novel therapeutic approaches involving CDK4/6 inhibitors, MEK inhibitors, and antiangiogenic agents like bevacizumab are also investigated. Ongoing clinical trials are striving to enhance LGSC treatment strategies, offering valuable insights for future therapeutic advancements in this challenging ovarian cancer subtype., Competing Interests: GG, JS, GO, AS, LB, and AM were employed by company Oncoclínicas&Co – Medica Scientia Innovation Research (MEDSIR). The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Giannecchini, da Silva, de Oliveira Bretas, dos Santos, Baltar and de Melo.)

Clinical research is the cornerstone of improvements in cancer care. However, it has been conducted predominantly in high-income countries with few clinical trials available in Brazil and other low-and-middle-income countries (LMIC). Of note, less than one-third of registered clinical trials addressing some of the most commonly diagnosed cancers (breast, lung and cervical) recruited patients from LMIC in the last years. The Institute Project CURA promoted the fourth CURA meeting, discussing barriers to cancer clinical research and proposing potential solutions. A meeting was held in São Paulo, Brazil, in June 2023 with representatives from different sectors: Brazilian Health Regulatory Agency (Anvisa), National Commission of Ethics in Research (CONEP), non-governmental organisations, such as the Latin American Cooperative Oncology Group, the Brazilian Society of Clinical Oncology (SBOC), Contract Research Organisations, pharmaceutical companies and investigators. A total of 16 experts pointed out achievements as shortening the time of regulatory processes involving Anvisa and CONEP, development of staff training programs, maintenance of the National Program of Oncological Attention (PRONON), and the foundation of qualified centres in North and Northeast Brazilian regions. Participants also highlighted the need to be more competitive in the field, which requires optimising ongoing policies and implementing new strategies as decentralisation of clinical research centres, public awareness campaigns, community-centered approaches, collaborations and partnerships, expansion of physicians-directed policies, exploring the role of the steering committee. Active and consistent reporting of the initiatives might help to propagate ongoing advances, increasing Brazilian participation in clinical cancer research. Engagement of all players is crucial to maintain continuous progress with further improvements in critical points including regulatory timelines and increments in qualified human resources which aligned with new educational initiatives focused on physicians and the general population will expand access to cancer clinical trials in Brazil., Competing Interests: Heloisa Resende has received research funding from Novartis and Roche, all outside the scope of this manuscript. Gustavo Werutsky has received research funding from AstraZeneca/MedImmune, Bristol-Myers Squibb Brazil, Pfizer, Roche and Roche/Genentech, all outside the scope of this manuscript. Has consulting or advisory role at Merck. Carlos H Barrios has received research funding from AB Science, Abbvie, Abraxis BioScience, Amgen, Asana Biosciences, Astellas Pharma, AstraZeneca, Biomarin, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Clinica Atlantis, Covance, Daiichi Sankyo, Exelixis, GlaxoSmith-Kline, Halozyme, ImClone Systems, INC Research, inVentiv Health, Janssen, LEO Pharma, Lilly, Medivation, Merck, Merck KGaA, Merrimack, Millennium, Mylan, Novartis, Pfizer, PharmaMar, Polyphor, Roche/Genentech, Sanofi, Shanghai Henlius Biotech and Taiho Pharmaceutical, all outside the scope of this manuscript. Has consulting or advisory role at AstraZeneca, Boehringer Ingelheim, Eisai, GlaxoSmithKline, Libbs, Lilly, MSD Oncology, Novartis, Pfizer, Roche/Genentech and United Medical. Has stock and other ownership interests in MedSIR and Tummi. All other authors have no conflicts of interest to disclose., (© the authors; licensee ecancermedicalscience.)

Aims: The objective of the study was to evaluate two translucent resin composite systems for customizing light-polymerized fiber posts with light-emitting diode (LED) curing units regarding adhesion using conventional cement at 24 h and 6 months., Settings and Design: This was an experimental in vitro study., Methods: Forty roots were prepared and divided into four groups ( n = 10): ZV-Z350 resin and LED Valo; ZR-Z350 resin and LED Radii-Cal; OV-Opallis resin and LED Valo; and OR-Opallis resin and LED Radii-Cal. The fiber post was customized and cemented with conventional resin cement and was photoactivated by two different sources., Statistical Analysis Used: The data were subjected to two-way ANOVA and Tukey's post hoc tests ( P = 0.05). The data regarding the pattern of adhesive failures were described in terms of the frequency of occurrence in each third of the postspace., Results: Both at 24 h and 6 months, bond strength among groups was similar, regardless of the analyzed postspace 3 rd ( P > 0.05). Adhesive failure Type 4 was the most frequent in all thirds., Conclusions: Customizing the fiber post with Z350 and Opallis has the same effect on bond strength and adhesive failure pattern, regardless of the LED curing units used for photopolymerization., Competing Interests: There are no conflicts of interest., (Copyright: © 2024 Journal of Conservative Dentistry and Endodontics.)

While the positive impact of early palliative care on the quality of life of cancer patients is well established, there is a noticeable research gap in developing countries. This study sought to determine the impact of an outpatient palliative care (OPC) program on the location of death among patients in Brazil. This was a retrospective study including patients with cancer who died between January 2022 and December 2022 in 32 private cancer centers in Brazil. Data were collected from medical records, encompassing demographics, cancer characteristics, and participation in the OPC program. The study involved 1980 patients, of which 32.3% were in the OPC program. OPC patients were predominantly younger (average age at death of 66.8 vs. 68.0 years old, p = 0.039) and composed of women (59.4% vs. 51.3%, p = 0.019) compared to the no-OPC patients. OPC patients had more home/hospice deaths (19.6% vs. 10.4%, p < 0.001), and participation in the outpatient palliative care program strongly predicted home death (OR: 2.02, 95% CI: 1.54-2.64). Our findings suggest a significant impact of the OPC program on increasing home and hospice deaths among patients with cancer in our sample. These findings emphasize the potential of specialized OPC programs to enhance end-of-life care, particularly in low-resource countries facing challenges related to social and cultural dimensions of care and healthcare access.

Objective: To assess the clinical communication characteristics of pharmacy undergraduates, estimate differences in this specific competency, and produce recommendations for further education and training., Methods: Analysis of communication competence between 110 pharmacy students in the last graduation year from each of the 5 Brazilian regions and a simulated patient with complaints of mild allergic rhinitis passive of resolution with non-prescription medicines. The simulated appointment was recorded, and the video was analyzed using the 2 main elements: biomedical/task-focused and socio-emotional exchange of the Roter Interaction Analysis System., Results: The total of utterances/speech from the pharmacist to the patient was 183.4; there was a statistically significant difference according to the Brazilian region. In the consultation, the frequency with which pharmacy students returned to the segment was evaluated, with a total mean clinical history segment 2 of mean 5.60; in segment 4, which is the counseling phase, an average of 4.80. In the task codes and the socio-emotional codes, there was a statistically significant difference between the codes when compared by region. We compare by sex because it is said that women talk more than men. There was a statistically significant difference in socio-emotional code and biomedical/focused and task being higher for women., Conclusion: The level of communication competence of students should be that desired for graduation, in all regions. There seems to be a difference between training and level of competence. Considering gender, although the consultation time is similar, it appears that the quality of communication is higher for women., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Federal University of São João Del-Rei and the Coordination Program of Professional Improvemet of Higher Education (CAPES) for financial assistance and the Minas Gerais State Research Support Foundation (FAPEMIG)., (Copyright © 2024 American Association of Colleges of Pharmacy. Published by Elsevier Inc. All rights reserved.)

Objective: This study aimed to explore trends in cervical cancer (CC) incidence and mortality rates according to race/skin color in Brazil focusing on the seriousness of the racial disparity., Methods: Data from Brazilian Population-Based Cancer Registries (PBCRs) were analyzed for trends in incidence between 2010 and 2015. For mortality, data from the National Mortality Information System were retrieved between 2000 and 2020. A self-declaration on race/skin color was collected following the classification proposed by the Brazilian Institute of Geography and Statistics - white, black, brown/mixed race, yellow, or indigenous. For the analysis, black and brown/mixed race were grouped as black., Results: Between 2010 and 2015, 10,844 new cases of CC were registered in the participating PBCRs, distributed among white women (49.6%), black (48.0%), and other race/skin color (2.3%). Compared with white counterparts, black women had a 44% higher risk of incident CC. As for mortality, between 2000 and 2020, 108,590 deaths from CC occurred nationwide. The mean age-adjusted mortality rates according to race/skin color were 3.7/100,000 for white, 4.2/100,000 for black, 2.8 for yellow, and 6.7 for indigenous women. Taking the mortality rates in white women as a reference, there was a 27% increase in death risk in black women (RR = 1.27) and 82% in indigenous women (RR = 1.82)., Conclusion: These findings suggest that the higher rates of incidence and mortality from CC in vulnerable populations of black and more impactfully indigenous women in Brazil remain alarming. More efficient HPV vaccination strategies synchronized with well-conducted Pap smear-based screening should be prioritized in these more vulnerable populations., (© 2023. W. Montague Cobb-NMA Health Institute.)

Bauhinia ungulata is an antioxidant medicinal plant that has been manipuled in Brazil to lower glycemic index as well is for alternative treatment for diabetes. Therefore, the present hearch has aimed to investigates the antioxidant effects of the essential oil of Bauhinia ungulata L. (EOBU) collected in Amazon region better specified in Boa Vista, Roraima, Brazil, located in the Amazon region. Gas chromatography had been used to characterize the components, and antioxidant assays such as DPPH, TAC, reducing power, Fe 2+ chelation, and total phenols had also been performed. The major constituents had molecularly anchored with the human catalase (CAT) enzyme, and maltol has showed as a positive control. Among the 25 revealed components, the main ones have been α-bisabolol (27.2 %), β-Caryophyllene (12.5 %) and Epi-γ-eudesmol (13.6 %). The EOBU has comproved a TAC value of 618.79 mg of ascorbic acid equivalent, free radical scavenging capacity (DPPH) around 53.7 % and 65.27 %, Fe 2+ chelation capacity of 161±6 and 126.7±39.6, for 0.1 mg.mL -1 and 0.5 mg.mL -1 , respectively. The power around the EOBU has appeared percentages equals to 28.66 %, 44.6 %, and 77.03 % in the concentrations tested. As well as, 96.5 % of total phenols. The compounds α-bisabolol (-5.7±0.4 Kcal.mol -1 ) and β-caryophyllene (-6.1±0.5 Kcal.mol -1 ) have showed good interaction with CAT compared to Maltol (-4.4±0.4 Kcal.mol -1 ). The present work has demonstrated that EOBU functions as a potent antioxidant, capable of scavenging free radicals and reducing oxidative stress damage., (© 2023 Wiley-VHCA AG, Zurich, Switzerland.)

Purpose: Immunotherapy and chemotherapy combinations have shown activity in endometrial cancer, with greater benefit in mismatch repair (MMR)-deficient (dMMR) than MMR-proficient (pMMR) disease. Adding a poly(ADP-ribose) polymerase inhibitor may improve outcomes, especially in pMMR disease., Methods: This phase III, global, double-blind, placebo-controlled trial randomly assigned eligible patients with newly diagnosed advanced or recurrent endometrial cancer 1:1:1 to: carboplatin/paclitaxel plus durvalumab placebo followed by placebo maintenance (control arm); carboplatin/paclitaxel plus durvalumab followed by maintenance durvalumab plus olaparib placebo (durvalumab arm); or carboplatin/paclitaxel plus durvalumab followed by maintenance durvalumab plus olaparib (durvalumab + olaparib arm). The primary end points were progression-free survival (PFS) in the durvalumab arm versus control and the durvalumab + olaparib arm versus control., Results: Seven hundred eighteen patients were randomly assigned. In the intention-to-treat population, statistically significant PFS benefit was observed in the durvalumab (hazard ratio [HR], 0.71 [95% CI, 0.57 to 0.89]; P = .003) and durvalumab + olaparib arms (HR, 0.55 [95% CI, 0.43 to 0.69]; P < .0001) versus control. Prespecified, exploratory subgroup analyses showed PFS benefit in dMMR (HR [durvalumab v control], 0.42 [95% CI, 0.22 to 0.80]; HR [durvalumab + olaparib v control], 0.41 [95% CI, 0.21 to 0.75]) and pMMR subgroups (HR [durvalumab v control], 0.77 [95% CI, 0.60 to 0.97]; HR [durvalumab + olaparib v control] 0.57; [95% CI, 0.44 to 0.73]); and in PD-L1-positive subgroups (HR [durvalumab v control], 0.63 [95% CI, 0.48 to 0.83]; HR [durvalumab + olaparib v control], 0.42 [95% CI, 0.31 to 0.57]). Interim overall survival results (maturity approximately 28%) were supportive of the primary outcomes (durvalumab v control: HR, 0.77 [95% CI, 0.56 to 1.07]; P = .120; durvalumab + olaparib v control: HR, 0.59 [95% CI, 0.42 to 0.83]; P = .003). The safety profiles of the experimental arms were generally consistent with individual agents., Conclusion: Carboplatin/paclitaxel plus durvalumab followed by maintenance durvalumab with or without olaparib demonstrated a statistically significant and clinically meaningful PFS benefit in patients with advanced or recurrent endometrial cancer.

Background: Merkel cell carcinoma (MCC) comprises a rare malignant primary skin tumor presenting neuroendocrine differentiation. Recently, agents blocking the programmed cell death protein 1 and programmed cell death protein ligand 1 pathway (PD-1/PD-L1) have demonstrated objective and durable tumor regressions in patients presenting advanced MCC. This study aimed to describe the sociodemographic, clinical, and histopathological characteristics of MCC patients, also assessing the prevalence of PD-L1 expression and Merkel cell Polyomavirus (MCPyV), as well as their prognostic roles., Methods: Data from patients diagnosed with MCC between 1996 and 2019 at a reference cancer center in Rio de Janeiro, southeastern Brazil, were evaluated in a retrospective study. Tumor samples were tested for MCPyV and PD-L1 employing immunohistochemistry. Survival analyses were carried out employing the Kaplan-Meier method and curves were compared using the log-rank test. A multiple semiparametric Cox model was used. Values p < 0.05 were considered significant., Results: A total of 65 patients were included in the study, with a mean age at diagnosis of 72 (standard deviation 13.9). A total of 56.9% (37/65) of the patients were male, 86.2% (56/65) were white, and 56.9% (37/64) were illiterate or with incomplete elementary school. MCPyV immunohistochemistry was positive in 29 cases (44.6%) and PD-L1 positivity was ≥ 1% in 42 cases (64.6%). Significant associations between MCPyV and PD-L1 expression ≥ 1% (p = 0.003) and PD-L1 expression ≥ 5% (p = 0.005) were noted. Concerning the multivariate analysis, only education level and advanced MCC stage indicated statistically significant worse progression-free survival. Regarding overall survival (OS), being male, education level and advanced stage comprised risk factors. The estimated OS at 60 months for stages I to III was of 48.9% and for stage IV, 8.9%., Conclusions: This is the first large Brazilian cohort to assess the prevalence of MCPyV in MCC tumors, as well as PD-L1 expression and their associations. No correlations were noted between MCPyV infection or PD-L1 expression and survival rates., (© 2023. The Author(s).)

The Bauhinia ungulata, also known by its common name "pata de vaca", is one of the species used in Brazil for medicinal purposes, and is commonly used for the treatment of diabetes. In this study, the authors studied the interaction between the chemical constituents which are present in the essential oil of Bauhinia ungulata (EOBU), collected in Boa Vista-RR, Legal Amazon, and their effects on the enzyme acetylcholinesterase (AChE) in the essential oil. The analysis that we perform includes proton magnetic resonance ( 1 H NMR), enzymatic inhibition, molecular docking, in silico toxicity prediction, enrichment analysis, and target prediction for biological interactions. According to the tests performed on the essential oil, it obtained 100% inhibition of the enzyme AChE. During 1 H NMR experiments, it was found that α- Bisabolol, one of the main components, had a significant alteration in its chemical shift. A molecular docking analysis confirmed that this compound binds to the AChE enzyme, which confirms the 1 H NMR analysis. The results of this work showed that the major component of EOBU acted as a possible inhibitor of AChE enzyme in vitro and in silico assays. These results show that EOBU could be potentially applied in Alzheimer's disease treatment.

Despite enormous recent advances in stage IV melanoma treatment, it continues to have a significant mortality. Five-years survival is below 50% even when granted full access to effective therapeutic regimens. Considering the real world, mostly with low or medium-income countries like Brazil, where 75% of population depends on public health system receiving ineffective Dacarbazine chemotherapy, more than 95% of stage IV patients are dead before 5 years. Knowing the survival process of melanoma end-of-life time is imperative to help physicians to establish better symptoms control and improve the quality of death of these patients., Methods: Relative caregiver of melanoma end of life patients were invited to participate in a specific interview answering questions for the purpose of gathering information regarding symptoms and patients' complaints at the last 30 days, 7 days and at the day of death., Results: Although melanoma has a highest propensity for brain dissemination, seizure and focal neurological deficits were not a major complaint. Most of dying melanoma symptoms are shared among other solid terminality tumor process and get worse from 30 days to 7 days, but the majority of symptoms kept unchanged from 7 days till time to death. Wound bleeding and bad odor were the only complaints that got worse during the whole terminality process and could be improved with better commitment of assistant team., Conclusions: although a strong effort is made to control brain metastasis, local and regional open wound metastasis represents a major remediable complaint that should receive more attention at end-of-life melanoma patients., Competing Interests: CONFLICT OF INTEREST All the authors declare that they have no conflict of interest.

Purpose: This study aimed to describe the demographic and clinical characteristics of cancer patients with COVID-19, exploring factors associated with adverse outcomes., Patients and Methods: This retrospective cohort study methodically extracted and curated data from electronic medical records (EMRs) of numerous healthcare institutions on cancer patients diagnosed with a confirmed SARS-CoV-2 infection between May 2020 and August 2021, to identify risk factors linked to extended hospitalization and mortality. The retrieved information encompassed the patients' demographic and clinical characteristics, including the incidence of prolonged hospitalization, acute complications, and COVID-19-related mortality., Results: A total of 1446 cancer patients with COVID-19 were identified (mean [Standard deviation] age, 59.2 [14.3] years). Most patients were female (913 [63.1%]), non-white (646 [44.7%]), with non-metastatic (818 [56.6%]) solid tumors (1318 [91.1%]), and undergoing chemotherapy (647 [44.7%]). The rate of extended hospitalization due to COVID-19 was 46% (n = 665), which was significantly impacted by age (p = 0.012), sex (p = 0.003), race and ethnicity (p = 0.049), the presence of two or more comorbidities (p = 0.006), hematologic malignancies (p = 0.013), metastatic disease (p = 0.002), and a performance status ≥ 2 (p = 0.001). The COVID-19-related mortality rate was 18.9% (n = 273), and metastatic disease (<0.001), performance status ≥2 (<0.001), extended hospitalization (p = 0.028), renal failure (p = 0.029), respiratory failure (p < 0.001), sepsis (p = 0.004), and shock (p = 0.040) significantly and negatively influenced survival., Conclusion: The rate of extended hospitalization and COVID-19-specific death in cancer patients was notably high and could be influenced by comorbidities, cancer treatment status, and clinical fragility. These observations may aid in developing risk counseling strategies regarding COVID-19 in individuals diagnosed with cancer., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 da Silva et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The present study aimed was to evaluate the spatial variability of weed species by means of phytosociological parameters and their correlations with the physical-chemical soil properties, under semiarid climate conditions. Weed phytosociology and soil characterization were carried out in two areas one newly deforested area covering 8.86 ha, and one experimental agricultural area covering 24.7 ha; both in the semi-arid region of Brazil. Weed and soil were sampled by following georeferenced grids in each area. Biomass and the total number of weed individuals, as well as soil properties, were mapped by the ordinary Kriging method. The predominant herbaceous plants in the newly deforested area were Hexasepalum teres and Digitaria insularis. The weed species that predominated in the agricultural area were Cyperus rotundus L., Euphorbia heterophylla L. and Herissantia Crispa (L.) Brizicky; the latter species outstanding for dry biomass (873.5g). Spatial dependence was observed for the predominant species, except for Digitaria insularis. The spatial distribution of these weeds was conditioned by soil K+ contents in both areas, and by sand content for the experimental agricultural area. Therefore, these two soil attributes resulted key factors for weed infestation in this semi-arid region.

Background: Concern about disease exacerbations and fear of reactions after coronavirus disease 2019 (COVID-19) vaccinations are common in chronic urticaria (CU) patients and may lead to vaccine hesitancy., Objective: We assessed the frequency and risk factors of CU exacerbation and adverse reactions in CU patients after COVID-19 vaccination., Methods: COVAC-CU is an international multicenter study of Urticaria Centers of Reference and Excellence (UCAREs) that retrospectively evaluated the effects of COVID-19 vaccination in CU patients aged ≥18 years and vaccinated with ≥1 dose of any COVID-19 vaccine. We evaluated CU exacerbations and severe allergic reactions as well as other adverse events associated with COVID-19 vaccinations and their association with various CU parameters., Results: Across 2769 COVID-19-vaccinated CU patients, most (90%) received at least 2 COVID-19 vaccine doses, and most patients received CU treatment and had well-controlled disease. The rate of COVID-19 vaccination-induced CU exacerbation was 9%. Of 223 patients with CU exacerbation after the first dose, 53.4% experienced recurrence of CU exacerbation after the second dose. CU exacerbation most often started <48 hours after vaccination (59.2%), lasted for a few weeks or less (70%), and was treated mainly with antihistamines (70.3%). Factors that increased the risk for COVID-19 vaccination-induced CU exacerbation included female sex, disease duration shorter than 24 months, having chronic spontaneous versus inducible urticaria, receipt of adenovirus viral vector vaccine, having nonsteroidal anti-inflammatory drug/aspirin intolerance, and having concerns about getting vaccinated; receiving omalizumab treatment and Latino/Hispanic ethnicity lowered the risk. First-dose vaccine-related adverse effects, most commonly local reactions, fever, fatigue, and muscle pain, were reported by 43.5% of CU patients. Seven patients reported severe allergic reactions., Conclusions: COVID-19 vaccination leads to disease exacerbation in only a small number of CU patients and is generally well tolerated., (Copyright © 2023 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Melanoma is the most lethal skin cancer, and its incidence has increased worldwide. About 10% of cases are classified as hereditary melanoma (HM). CDKN2A and CDK4 are the major high-risk genes. Families are also more prone to develop pancreatic cancer, and different forms of oncological surveillance are recommended., Objectives: Describe the prevalence of CDKN2A/CDK4 germline mutations in melanoma-prone patients and their phenotypic and histopathological features., Methods: A total of 69 patients meeting the clinical criteria for HM were included in this cross-sectional descriptive study. Amplification by PCR and genomic sequencing were used. The variants were classified according to American College of Medical Genetics (ACMG) criteria., Results: The mean age at first diagnosis of melanoma was 44.8 years (SD ± 17.83). Most patients had phototype II (44.9%), more than 50 melanocytic nevi (76.8%), atypical nevus syndrome (72.5%), history of sunburn (76.8%), and multiple primary melanomas without a family history of this tumor (74.3%). Two hundred melanomas were observed. Most tumors had a Breslow index ≤1.0 mm (84.5%), location in the trunk (60.5%), and superficial spreading histological subtype (22.5%). Four variants were found in CDKN2A exons in seven patients (c.305C>A, c.26T>A, c.361G>A e c.442G>A), two variants in the 5'UTR region in five patients (c.-25C>T and c.-33G>C), and two variants in the 3'UTR region in 21 patients (c.*29C>G and c.*69C>T). One likely pathogenic variant (c.305C>A) was identified in one patient (1.4%). No variant was found in CDK4., Conclusion: The prevalence of CDKN2A mutations was 1.4% in Brazilian patients meeting clinical criteria for HM., (© 2023 the International Society of Dermatology.)

Purpose: In patients with primary congenital glaucoma (PCG), elevated intraocular pressure (IOP) causes abnormal eye growth. This study compared the outcomes of children with PCG who underwent ab externo trabeculotomy (TROC) at age ≤ 6 months (early TROC) and of those who underwent TROC at age > 6 months (delayed TROC)., Methods: Intraocular pressure, horizontal corneal diameter (HCD), central corneal thickness (CCT) and axial length (AL) were compared before TROC and at 1-, 3-, 6- and 12-month follow-up visits between the groups of children who underwent TROC until or after 6 months of age. The ALs of these groups were also compared with the ALs of healthy age-matched eyes examined under the same conditions., Results: Trabeculotomy was performed in 43 children: 18 (33 eyes) aged 6 months (group 1) and 25 (37 eyes) aged >6 months (group 2); the mean ages were 86.56 ± 53.64 and 504.48 ± 448.14 days, respectively. The mean pre- and 12-month postoperative IOP values were 15.97 ± 4.78/16.62 ± 4.85 and 9.77 ± 2.88/10.93 ± 4.83 mmHg, respectively. Delayed TROC was associated with abnormal AL in 31 (88.6%) out of 37 eyes, while after early TROC, only 13 (41.9%) out of 33 eyes had abnormal AL (chi-square, 8.00; p = 0.03). In multivariable analysis, each 1-mmHg increase in preoperative IOP was associated with a 0.25-mmHg increase at 12 months (p = 0.04). On average, the mean IOP of the delayed TROC group was higher than that of the early TROC group by 3.72 mmHg at postoperative month 12 (95% CI = 0.44-6.99; p = 0.02)., Conclusion: Compared with delayed TROC, early TROC is associated with reduced IOP and substantially reduced incidence of abnormal AL at postoperative month 12., (© 2022 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Objective:  To analyze the outcomes of a cohort of patients with high-risk histologies of endometrial cancer (EC) treated at Instituto Nacional de Câncer (National Cancer Institute, INCA, in Portuguese), in Brazil., Materials and Methods:  We reviewed the medical records of patients with high-risk histologies of EC in any stage registered at INCA between 2010 and 2016 to perform a clinical and demographic descriptive analysis and to evaluate the outcomes in terms of recurrence and survival., Results:  From 2010 to 2016, 2,145 EC patients were registered and treated at INCA, and 466 had high-grade histologies that met the inclusion criteria. The mean age of the patients was 65 years, 44.6% were Caucasian, and 90% had a performance status of 0 or 1. The most common histology was high-grade endometrioid (31.1%), followed by serous carcinoma (25.3%), mixed (20.0%), carcinosarcoma (13.5%), and clear cell carcinoma (9.4%). Considering the 2018 Fédération Internationale de Gynécologie et d'Obstétrique (International Federation of Gynecology and Obstetrics, FIGO, in French) staging system, 44.8%, 12.4%, 29.8%, and 12.9% of the patient were in stages I, II, III or IV respectively. Age (> 60 years), more than 50% of myoinvasion, higher stage, poor performance status, serous and carcinosarcoma histologies, and adjuvant treatment were independent factors associated with recurrence-free survival (RFS) and overall survival (OS) in the multivariate analysis., Conclusion:  The current findings reinforced the international data showing poor outcomes of these tumors, especially for serous and carcinosarcomas and tumors with advanced stages, with shorter survival and high recurrence rates in distant sites, independently of the FIGO stage. Adjuvant therapy was associated with better survival., Competing Interests: The authors have no conflict of interests to declare., (Federação Brasileira de Ginecologia e Obstetrícia. This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/).)

Introduction: Acute lymphoblastic leukemia (ALL) presents a poor prognosis in adults. The adoption of pediatric protocols has been changing this scenario, especially for adolescents and young adults (AYA)., Objective and Method: We aimed to evaluate a consecutive series of patients treated at the State Institute of Hematology of Rio de Janeiro between 2012 and 2020, focusing on the AYA subgroup., Result: The B-ALL was the most frequent subtype (81.6%) and AYA, the predominant age group (57.7%). The median overall survival (OS) was 9.4 months. High early mortality was observed and sepsis was the main cause of death. Better OS results were noted in AYA, in comparison to over 39y (13.3 × 6.2 months, respectively), the Berlin-Frankfurt-Münster (BFM) being the protocol of choice in this group., Conclusion: The use of the pediatric protocol seems to improve the OS of AYA, however, high rates of deaths from infection were observed, demonstrating the need for advances in the Brazilian public system clinical support., Competing Interests: Conflicts of interest None., (Copyright © 2022 Associação Brasileira de Hematologia, Hemoterapia e Terapia Celular. Published by Elsevier España, S.L.U. All rights reserved.)

Background: Increased global cancer incidence rates have led to a growing demand for cancer diagnosis and treatment, as well as basic and clinical research on the subject. The expansion of clinical cancer trials beyond the borders of highly developed countries has aided the arrival of these assessments in South American countries. In this context, this study's objective is to highlight clinical cancer trial profiles developed and sponsored by pharmaceutical companies and conducted in South American countries from 2010 to 2020., Methods: This study comprises descriptive and retrospective research conducted following a search for clinical trials (phases I, II and III), registered at clinicaltrials.gov, carried out in Latin American countries and sponsored by pharmaceutical companies ("Argentina", "Brazil", "Chile", "Peru", "Colombia", "Ecuador", "Uruguay", "Venezuela", "Paraguay", "Bolivia"), registered between 1 January 2010 and 31 December 2020. A total of 1451 clinical trials were retrieved, of which 200 trials unrelated to cancer were excluded and 646 duplicates were removed, leading to a final total of 605 clinical trials employing qualitative and quantitative analyses., Results: A 122% increase in the number of clinical trial registrations from 2010 to 2020 was noted, with a prevalence of phase III studies (431 trials of a total of 605). Lung (119), breast (100), leukemia (42), prostate (39) and melanoma (32) were the main cancers tested for new drugs., Conclusions: The data reported herein indicate the need for strategic basic and clinical research planning that considers South American epidemic cancer profiles.

Purpose: This study aimed to describe the clinical and demographic profile of cervical cancer patients exploring risk factors for prolonged use of opioids., Methods: The database of the Brazilian National Cancer Institute was queried out and 214 women with cervical cancer diagnosed between January 2014 and December 2015 who underwent isolated external beam radiation therapy (EBRT) or chemoradiotherapy (CRT) with complete response were included. Patients who no longer used opioids 6 months after completion of radiation therapy were classified as stoppers; patients who continued using opioids were non-stoppers. Variables were comparatively evaluated as risk factors for prolonged use of opioids., Results: The median age was 49.4 years. Most women were non-white (64.5%) and had ECOG Performance Status (PS) ≥ 1 (76.6%), International Federation of Gynecology and Obstetrics (FIGO) stage II-III (84.1%), and squamous cell carcinoma (82.7%). Smoking and alcohol consumption rates were, respectively, 44.9% and 39.7%. The median time from diagnosis to the onset of EBRT was 111 days (interquartile range 66.2). Most patients underwent CRT (88.8%). The rate of non-stoppers was 65.0%. By multivariate analysis, prescription of strong opioids (p = 0.005) and disease recurrence (p < 0.001) were suggested as independent factors for prolonged use of opioids., Conclusion: The rate of prolonged use of opioids after radiotherapy is alarming. Prescription of strong opioids and disease recurrence might be independent risk factors for its persistent use., Implications for Cancer Survivors: These results reveal an unmet and urgent need to implement public multiprofessional support programs with well-established protocols for dependence withdrawal, as well as stricter national measures of control in opioid prescription., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Uterine Carcinosarcomas (UCS) are a rare type of cancer composed of an admixture of high-grade carcinomatous and sarcomatous elements. Clinicopathological prognostic factors in UCS are well established, but studies that approach the impact of biomarkers in this unusual disease are scarce. The study objective was to evaluate the prevalence and prognostic impact of a panel of prominent biomarkers in uterine carcinosarcoma (UCS) using an immunohistochemical characterization with four biomarkers., Methods and Findings: The internal database of a single Brazilian institution was carefully explored to select women diagnosed with UCS who were submitted to surgery and postoperative chemotherapy with carboplatin and paclitaxel between January 2012 and December 2017. Tissue microarrays containing UCS samples were evaluated by immunohistochemistry for L1CAM, CDX2, p53 and microsatellite instability markers. A total of 57 cases were included. The mean age was 65.3 years (standard deviation, SD 7.0). L1CAM was negative (score 0, no staining) in 27 (47.4%) patients. Of L1CAM-positive, 10 (17.5%) showed weak (score 1, <10%), 6 (10.5%) showed moderate (score 2, between 10-50%), and 14 (24.6%) showed strong L1CAM staining (score 3, ≧50%). dMMR occurred in 3 (5.3%) cases. The p53 was aberrantly expressed in 15 (26.3%) tumors. CDX2 was positive in 3 (5.3%) patients. The three-year progression-free survival (PFS) rate in the general population of the study was 21.2% (95% CI: 11.7-38.1) and the three-year overall survival (OS) rate was 29.4% (95% CI: 18.1-47.6). By multivariate analysis, the presence of metastases and CDX2-positive were significantly associated with poorer PFS (p < 0.001 and p = 0.002, respectively) and OS (p < 0.001 and p = 0.009, respectively)., Conclusion: The strong influence of CDX2 on prognosis requires further investigation. Biological or molecular variability may have impaired the assessment of the impact of the other markers on survival., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 da Silva et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Merkel cell carcinoma is a rare skin cancer with neuroendocrine differentiation. The risk factors include sun exposure, advanced age, immunosuppression (such as transplant recipients, patients with lymphoproliferative neoplasms, or patients with HIV), and Merkel cell polyomavirus infection. Clinically, Merkel cell carcinoma appears as a cutaneous or subcutaneous plaque or nodule, but this tumor diagnosis is rarely made clinically. Therefore, histopathology and immunohistochemistry are usually necessary. Primary tumors without evidence of metastases are treated with complete surgical excision and appropriate surgical margins. The presence of occult metastasis in a lymph node is frequent and a sentinel lymph node biopsy should be performed. Postoperative adjuvant radiotherapy increases local tumor control. Recently, agents that block the PD-1/PD-L1 pathway have shown objective and durable tumor regression in patients with advanced solid malignancies. The first anti-PD-L1 antibody used in patients with Merkel cell carcinoma was avelumab, but pembrolizumab and nivolumab have also shown efficacy. This article describes the current state of knowledge of the epidemiology, diagnosis, and staging of Merkel cell carcinoma, as well as new strategies for its systemic treatment., (Copyright © 2023 Sociedade Brasileira de Dermatologia. Published by Elsevier España, S.L.U. All rights reserved.)

Introduction: Fatigue is a prevalent symptom among both cancer survivors and older adults. Negative consequences of fatigue include increased sedentary behavior, decreased physical activity and function, and lower quality of life. Few pharmacologic interventions improve fatigue. Our preclinical and clinical data show promising effects of a muscadine grape extract supplement (MGES) on oxidative stress, mitochondrial bioenergetics, the microbiome, and the symptom of fatigue. This pilot study seeks to translate these observations to cancer survivorship by testing the preliminary effect of MGE supplementation on older adult cancer survivors with self-reported fatigue., Materials and Methods: We designed a double-blinded placebo-controlled pilot study to evaluate preliminary efficacy of MGE supplementation versus placebo on fatigue among older adult cancer survivors (aged ≥65 years) who report baseline fatigue. Sixty-four participants will be enrolled and randomized 1:1 to twice daily MGES (four tablets twice daily) versus placebo for 12 weeks. The primary outcome is change in Patient-Reported Outcomes Measurement Information System (PROMIS) Fatigue score from baseline to 12 weeks. Secondary outcomes are change in self-reported physical function, physical fitness (6-min walk test), self-reported physical activity, global quality of life (QOL), and the Fried frailty index. Correlative biomarker assays will assess changes in 8-hydroxy-2 deoxyguanosine, peripheral blood mitochondrial function, inflammatory markers, and the gut microbiome., Discussion: This pilot study builds on preclinical and clinical observations to estimate effects of MGE supplementation on fatigue, physical function, QOL, and biologic correlates in older adult cancer survivors. Trial registration #: CT.govNCT04495751; IND 152908., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest to report., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Melanoma represents an increasing public health burden with extensive unmet needs in Latin America (LA). A mutation in the BRAF gene is present in approximately 50% of all melanomas in White populations and is a target of precision medicine, with the potential to dramatically improve patient outcomes. Thus, increased access to BRAF testing and therapy is LA must be explored. At a multi-day conference, a panel of Latin American experts in oncology and dermatology were provided with questions to address the barriers limiting access to testing for BRAF mutation in patients with melanoma in LA, who may be eligible for targeted therapy to improve their prognosis. During the conference, responses were discussed and edited until a consensus on addressing the barriers was achieved. Identified challenges included ignorance of BRAF -status implications, limited human and infrastructural resources, affordability and reimbursement, fragmented care delivery, pitfalls in the sample journey, and lack of local data. Despite the clear benefits of targeted therapies for BRAF -mutated melanoma in other regions, there is no clear path to prepare LA for a sustainable personalized medicine approach to this disease. Due to melanoma's time-sensitive nature, LA must aim to provide early access to BRAF testing and consider mutational status within treatment decision making. To this end, recommendations are provided and include establishing multidisciplinary teams and melanoma referral centers and improving access to diagnosis and treatment., Competing Interests: GC received: grants or had contracts from Novartis, Merck Sharp & Dohme, Pfizer, Roche/Genentech, Bristol Myers Squibb, Array, Springer, Grupo Español de Melanoma; consulting fees from Merck Sharp & Dohme, Novartis, Bristol Myers Squibb, Roche/Genentech; honoraria for presentations from Novartis, Merck Sharp & Dohme, Pfizer, Roche, Bristol Myers Squibb, Array, Springer, and Grupo Español de Melanoma; support for attending meetings from Novartis, Merck Sharp & Dohme, Bristol Myers Squibb, Roche; payment for board participation from Novartis, Merck Sharp & Dohme, Bristol Myers Squibb, Roche/Genentech. AM’s institution received grants from Clovis Oncology, Regeneron, Merck Sharp & Dohme, Bristol Myers Squibb, GlaxoSmithKline, AstraZeneca, Novartis, Amgen, and Roche for clinical trials. AM received payment for lectures from Merck Sharp & Dohme, Bristol Myers Squibb, GlaxoSmithKline, AstraZeneca, Novartis, Roche, Sanofi. Advisory Board participation from Merck Sharp & Dohme, Bristol Myers Squibb, GlaxoSmithKline, AstraZeneca, Novartis, Roche. RS received: consulting fees from Merck Sharp & Dohme and L’Oreal; payment for presentations from Merck Sharp & Dohme, Bristol Myers Squibb, Sanofi Genzyme, Pfizer, Merck Serono, Novartis; support from Bristol Myers Squibb for expert testimony; support for attending meetings from Sanofi Genzyme and Merck Sharp & Dohme. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Salman, de Melo, Rico-Restrepo, Rodriguez, Russi, Schmerling, Zambrano and Cinat.)