Dose dense versus 3 weekly AC during neoadjuvant chemoimmunotherapy for triple negative breast cancer.

Neoadjuvant pembrolizumab plus chemotherapy (P + CT) has emerged as a standard of care for stage II-III triple-negative breast cancer (TNBC). However, the best anthracycline-cyclophosphamide (AC) schedule remains to be determined. While the KEYNOTE-522 regimen employs AC every 3 weeks (q3w AC), previous studies have shown overall survival benefits of dose-dense regimens for early-stage breast cancer. The Neo-Real study (GBECAM-0123) is a real-world data effort evaluating patients with TNBC treated with neoadjuvant P + CT in ten cancer centers since July 2020. The objective of this analysis was to evaluate the effectiveness and safety of dose-dense AC (ddAC) versus q3w AC. Among 333 patients included until November 2023, 311 completed neoadjuvant therapy and 279 underwent surgery with pathology reports available; ddAC was used in 58.2% and q3w AC in 41.8% of the cases. Most patients (69.1%) had stage II TNBC. A pCR was observed in 65.4% with ddAC and 58.7% with q3w AC (P = 0.260), while RCB 0-1 occurred in 82.4% and 73.5%, respectively (P = 0.115). Patients with stage III disease had a numerically higher pCR with ddAC (59% vs 40%, P = 0.155), while pCR rates were similar regardless of AC regimen in stage II disease (66.6% vs 64.5%; P = 0.760). While no significant disparities in drug discontinuation was noted, ddAC showed a trend towards higher rates of grade ≥3 AE (40.5% vs. 30.7%, P = 0.092). The Neo-Real study could not rule out a difference between ddAC and q3w AC during neoadjuvant P + CT. The observation of a potentially higher pCR with ddAC in stage III disease warrants further investigation.

Comparison of PARPi efficacy according to homologous recombination deficiency biomarkers in patients with ovarian cancer: a systematic review and meta-analysis.

BACKGROUND: Mutations in the BRCA1/2 (BRCA) genes are associated with response to poly(ADP-ribose) polymerase (PARP) inhibitors (PARPi). In addition, there are different homologous recombination deficiency (HRD) biomarkers available in clinical practice [e.g., genome-wide loss-of-heterozygosity (gLOH) and myChoice® score] that identify patients who can benefit from PARPi. Inconsistencies in biomarkers used in PARPi clinical trials make it challenging to identify clinically relevant predictive biomarkers. This study aims to compare clinically available HRD biomarkers in terms of benefits from PARPi. METHODS: We performed database search for phase II or III randomized clinical trials comparing PARPi versus chemotherapy, and meta-analysis using generic inverse variance and a Random Effects model. Patients were classified according to their HRD status: (I) BRCAm (patients with BRCA mutation of germline or somatic origin); (II) non-BRCA HRD [patients BRCA wild-type (wt) with another HRD biomarker-gLOH or myChoice®]; and (III) homologous recombination proficiency (HRP) (BRCAwt and without HRD biomarkers). From those that were BRCAwt, we compared myChoice®+ with gLOH-high. RESULTS: Five studies (3,225 patients) analyzing PARPi in first line setting were included. Patients with BRCAmut had progression-free survival (PFS) with hazard ratio (HR) 0.33 [95% confidence interval (CI): 0.30-0.43]; patients with non-BRCA HRD had a PFS HR 0.49 (95% CI: 0.37-0.65), and patients with HRP had a PFS HR 0.78 (95% CI: 0.58-1.03). Eight studies (5,529 patients) with PARPi including first line and recurrence settings were included. BRCAmut had PFS HR 0.37 (95% CI: 0.30-0.48), BRCAwt & HRD 0.45 (95% CI: 0.37-0.55) and HRP 0.70 (95% CI: 0.57-0.85). Patients with BRCAwt & myChoice® ≥42 had PFS HR 0.43 (95% CI: 0.34-0.56), similar to patients with BRCAwt & gLOH-high with PFS HR 0.42 (95% CI: 0.28-0.62). CONCLUSIONS: Patients with HRD derived significantly more benefit from PARPi when compared to patients with HRP. The benefit of PARPi in patients with HRP tumors was limited. Careful cost-effectiveness analysis, and alternative therapies or clinical trial enrollment should strongly be considered for patients with HRP tumors. Among patients with BRCAwt, a similar benefit was found in patients with gLOH-high and those myChoice®+. The clinical development of further HRD biomarkers (e.g., Sig3) may help identify more patients who benefit from PARPi.

Modelo de parkinson por lesão unilateral induzida pela 6-hidroxidopamina: análises comportamentais e imunohistoquímicas / Parkinson model for unilateral injury induced by 6-hydroxidopamine: behavioral and immunohistochemistry analysis

Introdução: A doença de Parkinson é uma doença neurodegenerativa crônica complexa que afeta o sistema dopaminérgico e atinge cercade 3% da população mundial acima de 50 anos. Clinicamente, a doença de Parkinson não é diagnosticada antes da manifestação dessasdifi culdades locomotoras, o que contribuiu para o diagnóstico tardio da doença e a dominância de modelos animais de estudos baseadosnessas características. Embora o uso de modelos animais seja limitado em diversos aspectos, devido às diferenças genéticas, anatômicase funcionais entre murinos e humanos, muito do nosso conhecimento a respeito da patofi siologia da doença é devido ao uso destasferramentas. Objetivos: Estabelecer modelo de estudo da doença de Parkinson, reprodutível e validado por testes comportamentais eimuno-histoquímicos. Método: O modelo murino de lesão unilateral induzida pela 6-hidroxidopamina (6-OHDA) foi realizado por meio decirurgia estereotáxica para administração intracranicana, no feixe medial do encéfalo anterior (MFB). A toxina foi infundida a uma taxade 1uL/min, e a cânula foi deixada no lugar por 3 min antes da retirada. Para limitar os danos nos neurônios noradrenérgicos, cloridratode desipramina (10 mg/kg, i.p) foram administrados 30 min antes da injeção de 6-OHDA. Os animais controles foram submetidos aomesmo procedimento estereotáxico, mas com solução salina...

Introduction: Parkinson's disease is a complex chronic neurodegenerative disease, damaging the dopaminergic system and affectingabout 3% of the world population over 50 years. Clinically, Parkinson's disease is not diagnosed prior to the manifestation of theselocomotor diffi culties, thus contributing to the late disease diagnosis and to the dominance of animal models of studies based on thesecharacteristics. Although the use of animal models is limited in several aspects due to genetic, anatomical and functional differencesbetween murine and human, much of our knowledge about the pathophysiology of the disease is due to the use of these tools.Objectives: To establish Parkinson's disease study models, reproducible and validated by behavioral and immunohistochemical tests.Method: The murine model of unilateral lesion induced by 6-hydroxydopamine (6-OHDA) was performed by stereotactic surgery forintracranial administration in the medial bundle of the forebrain (MFB). The toxin was infused at a rate of 1µL/ min, and the cannulawas left in place for 3 min prior to withdrawal...

Introducción: La enfermedad de Parkinson es una enfermedad neurodegenerativa crónica compleja que afecta al sistema dopaminérgicoy alcanza cerca del 3% de la población mundial por encima de 50 años. Clínicamente, la enfermedad de Parkinson no se diagnostica antesde la manifestación de esas difi cultades locomotoras, lo que contribuyó al diagnóstico tardío de la enfermedad y la dominación de modelosanimales de estudios basados en esas características. Aunque el uso de modelos animales es limitado en diversos aspectos, debido a las...

Perfil epidemiológico dos pacientes idosos queimados internados em unidade de tratamento de queimados do Noroeste paulista / Epidemiological profile of burned elderly patients hospitalized in a reference hospital in the northwest of São Paulo / Perfil epidemiológico de los pacientes ancianos quemados y hospitalizados en un hospital de referencia del noroeste paulista

OBJETIVO: Analisar o perfil epidemiológico dos pacientes idosos internados na Unidade de Tratamento de Queimados (UTQ) do Hospital Padre Albino do município de Catanduva, SP. MÉTODO: Trata-se de um estudo transversal baseado na análise dos prontuários e do livro de registro da Unidade de Terapia de Queimados do Hospital Padre Albino. A coleta de dados ocorreu entre março de 2012 e março de 2013, sendo selecionados todos os idosos que passaram pela unidade. Foram coletados dados como: sexo, idade, local do acidente, período de internação, vícios apresentados pelos pacientes, comorbidades, agente agressor, profundidade da lesão, superfície da área queimada e evolução - que inclui enxertia, infecção e óbito. RESULTADOS: Houve predomínio de queimaduras em pacientes idosos do sexo masculino, tendo como local do acidente a própria casa. A maioria apresentava duas comorbidades associadas, sendo a principal a hipertensão arterial sistêmica. Chama direta foi o agente causal mais frequente, predominando queimaduras combinadas de 2o e 3o grau, sendo evidenciada elevada taxa de grandes queimados e necessidade de enxertia em alguns casos, seguida de alta possibilidade de infecção. CONCLUSÃO: O conhecimento do perfil epidemiológico é importante para medidas de prevenção, que devem ser tomadas por toda a comunidade. Além disso, com o conhecimento das principais comorbidades, características das queimaduras, condutas e evolução podem ser estabelecidas melhores estratégias de tratamento para o idoso.(AU)

OBJECTIVE: To analyze the epidemiological profile of the elderly patients hospitalized at the Burn Care Unit (BCU) of the Hospital Padre Albino in Catanduva-SP. METHOD: This is a retrospective study based on the analysis of the medical records from the Hospital Padre Albino's Burn Care Unit`s record book. For data collection it was used the period from March 2012 to March 2013, which were selected all elderly patients who passed through the unit. Data such as sex, age, the accident site, days of hospitalization comorbidities, agent, lesion depth, burn area and evolution, including grafting, infection and death were collected. RESULTS: There was a predominance of burns in elderly male patients, with the scene of the accident being the house itself. Most had two comorbidities, the main one was systemic hypertension; the direct flame is the most frequent causative agent, predominating combined burns of 2nd and 3rd degree, with evident high rate of major burns and the need for grafting in some cases, followed by high possibility of infection. CONCLUSION: The knowledge of the epidemiological profile is a matter of utmost importance to preventive measures that should be taken by the whole community. Also, with the knowledge of the main comorbidities, burn characteristics, behaviors and evolution, better treatment strategies can be established for the elderlies.

Objectivo: Analizar el perfil epidemiológico de los pacientes ancianos hospitalizados en la Unidad de Atención a Quemados del Hospital Padre Albino del municipio de Catanduva, Sao Paulo. Método: Se trata de un estudio retrospectivo basado en el análisis de la historia clínica y del libro de registros de la Unidad de Atención a Quemados del Hospital Padre Albino. La recolección de datos se hizo entre marzo de 2012 y marzo de 2013, periodo en que fueron seleccionadas todas las personas mayores que pasaron por la unidad. Los datos recolectados fueran: sexo, edad, lugar del accidente, días de internación adicciones que presentaban los pacientes, comorbilidades, agente agresor, profundidad de la lesión, superficie del área quemada y evolución, incluyéndose injerto, infección y muerte. Resultados: Se observó un predominio de quemaduras en los ancianos de sexo masculino, teniendo la propia casa como lugar del accidente. La mayoría tenía dos comorbilidades asociadas, principalmente hipertensión sistémica. La llama directa fue el causante más frecuente, ocasionando predominantemente quemaduras que combinan segundo y tercero grados, con evidente tasa de grandes quemados y necesidad de injerto en algunos casos, seguido de alta posibilidad de infección. Conclusión: El conocimiento del perfil epidemiológico es importante para las medidas preventivas que se deben tomar por toda la comunidad. Con el conocimiento de las principales comorbilidades, las características de las quemaduras, conductas y evolución, se pueden establecer mejores estrategias de tratamiento para las personas mayores.(AU)