Long-term outcomes of neoadjuvant immunotherapy plus chemotherapy in patients with early-stage triple-negative breast cancer: an extracted individual patient data and trial-level meta-analysis.

BACKGROUND: Neoadjuvant immunotherapy (nIO) has emerged as a treatment option for stage II-III triple-negative breast cancer (TNBC). While randomised clinical trials (RCTs) demonstrated pathological complete response rate benefit to nIO added to chemotherapy, additional data on long-term outcomes is warranted. We performed this analysis to evaluate long-term efficacy outcomes of nIO in TNBC. METHODS: We searched databases for RCTs evaluating nIO in early-stage TNBC. A meta-analysis of extracted individual patient data (EIPD) was performed to evaluate EFS and OS, with data from reported Kaplan-Meier plots. Additionally, we conducted a trial-level meta-analysis using fixed and random effects models. RESULTS: The literature search resulted in four included RCTs with available EFS or OS (KEYNOTE-522, IMpassion031, I-SPY2 and GeparNuevo). EIPD showed that the addition of nIO to chemotherapy provides statistically significant benefits in EFS (HR 0.62, 0.50-0.76; p < 0.001) and OS (HR 0.62, 0.46-0.82, p < 0.001). Number needed to treat to avoid one EFS or OS event in 4 years was 9 and 14, respectively. Trial-level meta-analysis yielded similar results (EFS: HR 0.64, 0.51-0.79; OS: 0.57, 0.37-0.89). CONCLUSIONS: Results show that nIO combined with chemotherapy can provide significant EFS and OS benefits, supporting its use as standard treatment for early-stage TNBC.

In vitro antibacterial activity of bioactive glass S53P4 on multiresistant pathogens causing osteomyelitis and prosthetic joint infection.

BACKGROUND: Conventional local treatment for medullary osteomyelitis (OM) includes insertion of antibiotic-loaded polymethylmethacrylate (PMMA) cement. Nevertheless, PMMA may delivery irregular concentration of antibiotic to surrounding tissue. We aimed to compare the in vitro antibacterial activity of Bioactive Glass (BAG) S53P4, which is a compound showing local antibacterial activity, to that of antibiotic-loaded PMMA against multidrug resistant bacteria from OM isolates. METHODS: We studied convenience samples of multidrug resistant (MDR) microorganisms obtained from patients presenting OM and prosthetic joint infection (PJI). Mixtures containing tryptic soy broth (TSB) and inert glass beads (2 mm), BAG-S53P4 granules (0.5-0.8 mm and < 45 mm) and Gentamicin or Vancomycin-loaded PMMA beads were inoculated with methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-resistant coagulase-negative Staphylococcus (MR-CoNS), Pseudomonas aeruginosa or Klebsiella pneumoniae isolates. Glass beads (2.0 mm) were used as a control. Antibacterial activity was evaluated by means of time-kill curve, through seeding the strains on blood agar plates, and subsequently performing colony counts after 24, 48, 72, 96, 120 and 168 h of incubation. Differences between groups were evaluated by means of two-way analysis of variance (ANOVA) and Bonferroni's t test. RESULTS: Inhibition of bacterial growth started soon after 48 h of incubation, reached zero CFU/ml between 120 and 168 h of incubation for both antibiotic-loaded PMMA and BAG S53P4 groups, in comparison with inert glass (p < 0.05). No difference regarding time-kill curves between antibiotic-loaded PMMA and BAG S53P4 was observed. CONCLUSIONS: BAG S53P4 presented antibacterial properties as much as antibiotic-loaded PMMA for MDR bacteria producing OM and PJI.

High Dose Chemotherapy With Autologous Stem Cell Transplant for Patients With Advanced Germ Cell Tumors: Real-World Evidence From a Tertiary Cancer Center in Brazil.

BACKGROUND: High-dose chemotherapy followed by stem cell transplant (HDCT) is potentially curative for patients with refractory germ cell tumors (rGCT). There is scarce real-world data supporting its implementation in low- and middle-income countries. We described the experience of our tertiary cancer center in Sao Paulo, Brazil. METHODS: We identified male patients ≥18 years-old with rGCT referred to HDCT after board discussion. Clinical data, including delays in HDCT protocol, were extracted from medical records, and survival outcomes were estimated using the Kaplan-Meier method. The log-rank test and Cox proportional hazard were used to determine effects on overall survival (OS). RESULTS: From January 2013 to January 2023, 34 patients were referred and considered eligible to receive 2 cycles of HDCT. Most patients had primary testicular tumors (82%), nonseminomatous histology (88%), and poor International Germ Cell Collaborative Group (IGCCCG) (79%). Twenty-three patients received HDCT (1 cycle, n = 8; 2 cycles, n = 15). Main reasons for not receiving any HDCT were death due to progressive disease (n = 1), performance deterioration (n = 7), and failure of stem cell mobilization (n = 3). OS at 2 years was 36.7% for the eligible population, 56.1% for patients who underwent at least 1 HDCT, and 77.1% for those who had ≥2 cycles. The 2-year OS rate for patients not given HDCT was 0%. All patients had delays in protocol, and poor-risk patients had longer intervals from referral to protocol initiation (0.7 vs. 1.8 month, P < .01). CONCLUSION: Outcomes of patients who received ≥1 HDCT were encouraging; however, only 15 from 34 eligible patients were able to receive the planned 2 cycles of HDCT. Further strategies to minimize treatment delays in low- and middle-income countries are needed.

Predicting survival in metastatic non-small cell lung cancer patients with poor ECOG-PS: A single-arm prospective study.

BACKGROUND: Patients with advanced non-small cell lung cancer (NSCLC) are a heterogeneous population with short lifespan. We aimed to develop methods to better differentiate patients whose survival was >90 days. METHODS: We evaluated 83 characteristics of 106 treatment-naïve, stage IV NSCLC patients with Eastern Cooperative Oncology Group Performance Status (ECOG-PS) >1. Automated machine learning was used to select a model and optimize hyperparameters. 100-fold bootstrapping was performed for dimensionality reduction for a second ("lite") model. Performance was measured by C-statistic and accuracy metrics in an out-of-sample validation cohort. The "lite" model was validated on a second independent, prospective cohort (N = 42). Network analysis (NA) was performed to evaluate the differences in centrality and connectivity of features. RESULTS: The selected method was ExtraTrees Classifier, with C-statistic of 0.82 (p < 0.01) and accuracy of 0.81 (p = 0.01). The "lite" model had 16 variables and obtained C-statistic of 0.84 (p < 0.01) and accuracy of 0.75 (p = 0.039) in the first cohort, and C-statistic of 0.706 (p < 0.01) and accuracy of 0.714 (p < 0.01) in the second cohort. The networks of patients with lower survival were more interconnected. Features related to cachexia, inflammation, and quality of life had statistically different prestige scores in NA. CONCLUSIONS: Machine learning can assist in the prognostic evaluation of advanced NSCLC. The model generated with a reduced number of features showed high accessibility and reasonable metrics. Features related to quality of life, cachexia, and performance status had increased correlation and importance scores, suggesting that they play a role at later disease stages, in line with the biological rationale already described.

Letter to the editor: radiomics analysis for predicting pembrolizumab response in patients with advanced rare cancers.

A commentary on the original research article: 'Radiomics analysis for predicting pembrolizumab response in patients with advanced rare cancers'. Of note, the predictor selection process, the cross-validation method, along with the lack of final testing of the developed model with a separated data set may mask overfitting, overestimating performance metrics.

Promoção à saúde e prevenção de acidentes na infância: uma ação de estudantes de medicina / Health promotion and accident prevention in childhood: an intervention of medical students

Introdução: A promoção à saúde é um grande desafio no Sistema Único de Saúde. A realização de ações de promoção faz parte das competências necessárias ao egresso do curso de medicina, segundo as Diretrizes Curriculares Nacionais para o Curso de Graduação em Medicina (DCN). Objetivo: Este trabalho visa descrever a elaboração e implementação de ação lúdica, visando educação em saúde com enfoque em prevenção de acidentes domésticos na infância, por parte de alunos do primeiro ano do curso de medicina da Faculdade de Ciências Médicas da Santa Casa de São Paulo (FCMSCSP). Métodos: O uso da metodologia da problematização conduziu a construção do projeto, desde o reconhecimento do território da Unidade Básica de Saúde (UBS), discussão de problemas encontrados, levantamento bibliográfico, elaboração de hipóteses de solução e implementação de ação. Resultados: Os alunos do primeiro ano de medicina optaram por trabalhar com o tema de prevenção de acidentes domésticos na infância, em parceria com a UBS e com organização não-governamental (ONG) da região, que realiza atividades educativas e de lazer com crianças em idade escolar, após o horário da aula. Os alunos construíram jogos discutindo a prevenção de acidentes e folheto explicativo para pais e responsáveis. Foi realizada gincana em novembro de 2012, em que os alunos coordenaram os jogos com as crianças que utilizam a ONG. Os alunos construíram narrativa sobre a percepção da atividade, com boa avaliação da ação. Discussão: Há evidências do benefício de inserir o aluno precocemente em ações na comunidade, principalmente na participação ativa de atividades de promoção à saúde, visando à aprendizagem significativa. A problematização é estratégia privilegiada de ensino do tema de promoção à saúde e à construção das competências necessárias à elaboração destas ações.

Introduction: Health promotion is a great challenge in the Brazilian National Health System. The implementation of health promotion actions is part of the necessary skills of medical school undergraduates, according to the National Curriculum Guidelines for Undergraduate Medicine (DCN). Objective: This study aims to describe the development and implementation of games, seeking health education focusing on prevention of domestic accidents in childhood, made by students of the first year of medical school, Faculty of Medical Sciences of Santa Casa de São Paulo (FCMSCSP). Methods: The methodology of problematization led to construction of the project, started with the recognition of the territory of primary care service, discussion of found problems, evaluation of medical literature, towards the formulation of possible solutions and implementing an prevention action. Results: The first year medical students have chosen to work with prevention of domestic accidents in childhood, in partnership with UBS and a nongovernmental organization in the region, which conducts educational and recreational activities with children, in the after-school period. The students put up games discussing accident prevention and a leaflet for parents and guardians. Tournament was held in November 2012, in which medical students coordinated games with the children. Students constructed narrative about their perception of activity, with good evaluation of the health promotion action. Discussion: There is evidence of the benefit of early introduction of medical students in the community context, especially in active participation of health promotion activities, aiming to meaningful learning. The problematization strategy is a privileged teaching method aiming actions of health promotion and building the necessary skills for the production of these actions.