This study primarily aimed to generate real-world evidence (RWE) on the profile and first-line treatment (1LT) patterns of patients with advanced (unresectable Stage III/metastatic) cutaneous melanoma initiated on immuno-oncology (IO)- or targeted therapy (TT)-based 1LT between 1 January 2015 and 1 January 2018 (index period), in routine settings of Greece. This was a multicenter, retrospective chart review study. Eligible consented (unless deceased, for whom consent was waived by the hospital) patients were consecutively included by six oncology clinics. The look-back period extended from informed consent or death to initial melanoma diagnosis. Between 9 Junuary 2021 and 9 February 2022, 225 eligible patients (all Caucasians; 60.4% male; 35.6% diagnosed with de novo advanced melanoma) were included. At 1LT initiation, median age was 62.6 years; 2.7/6.7/90.7% of the patients had Stage IIIB/IIIC/IV disease and 9.3% were unresected. Most frequent metastatic sites were the lung (46.7%), non-regional nodes (33.8%), and liver (20.9%). Among patients, 98.2% had single primary melanoma, 45.6% had disease localized on the trunk, and 63.6% were BRAF-mutant. Of the patients, 45.3% initiated 1LT with an IO-based, 53.3% with a TT-based regimen, and three patients (1.3%) received TT-based followed by IO-based or vice versa. Most common 1LT patterns (frequency ≥10%) were BRAFi/MEKi combination (31.6%), anti-PD-1 monotherapy (25.3%), BRAFi monotherapy (21.8%), and anti-CTLA-4 monotherapy (17.8%). Most frequent regimens were Dabrafenib+Trametinib in 25.3%, and monotherapies with Pembrolizumab/Ipilimumab/Vemurafenib/Dabrafenib in 23.6/17.8/11.1/10.7% of patients, respectively. SUMMER provides RWE on 1LT strategies and profile of patients initiated 1L IO- or TT-based therapy in Greece during the 3-year index period.

Aim: Inhibitors of dopamine-β-hydroxylase (DβH), such as zamicastat, emerged as promising drugs for pulmonary arterial hypertension (PAH). This study intended to validate the mechanism of action of zamicastat by studying its effect on the overdrive of sympathetic nervous system (SNS). Methods: This was a single-centre, prospective, double-blind, randomised, placebo-controlled, crossover study, with 400 mg zamicastat, in 22 healthy male subjects. Cold pressor test (CPT) was performed at screening and each treatment period at day 1 and day 10. The concentration of dopamine (DA), epinephrine (EPI), norepinephrine (NE) in plasma and 24h-urine, and DβH activity in plasma were measured. Results: For zamicastat compared to placebo, the difference between cold stimulus and rest phases on the change from baseline to day 10 of CPT showed an estimated decrease of -4.62 mmHg for systolic blood pressure (SBP; p=0.020). Zamicastat caused a decrease of -2.62 mmHg in mean arterial pressure (MAP) response to cold stimulus during CPT (p=0.025). At day 10, zamicastat elicited a statistically significant increase of 12.63 ng/L (p=0.040) and 19.22 ng/L (p=0.001) in plasma DA, before CPT and after CPT, and a significant estimated increase in plasma EPI change from baseline after CPT (p=0.040). Inhibition of plasma DβH activity ranged from 19.8% to 25.0%. At day 10, statistically significant reductions in 24-hour urinary excretion of EPI (p=0.002) and NE (p=0.001) were observed. Conclusions: Zamicastat decreased SBP and MAP response to cold stimulus during CPT, evidencing its effect on the overdrive sympathetic response to cold stimulus.

Introdução: O câncer de mama (CM) é um dos tipos de câncer mais prevalentes e é a primeira causa de morte por tumores malignos entre as mulheres em todo o mundo. Novas terapias recebem aprovação regulatória anualmente, e os sistemas de saúde são desafiados a adaptar sua infraestrutura, metodologias e políticas de reembolso para permitir o amplo acesso. A combinação de dose fixa subcutânea (SC), pronta para uso, de Pertuzumabe e Trastuzumabe (pertuzumabe, trastuzumabe e hialuronidase- zzxf; PH FDC SC) foi aprovada em dezembro de 2021 pela Anvisa e em fevereiro de 2022 pela CMED, para tratar pacientes adultos com câncer de mama inicial e metastático HER2-positivo. O estudo pivotal (PHranceSCa) Fase 2 de PHESGO FDC SC demonstrou que a maioria dos pacientes preferem PHESGO FDC SC em comparação a combinação de Pertuzumabe intravenoso (IV) e Trastuzumabe (IV) (SC: 85,0%; IV: 13,8%; sem preferência: 1,3%). Objetivos: Investigar as preferências pelas vias de administração medicamentosa por infusão (SC ou IV) entre pacientes e profissionais de saúde (PS) (médicos, enfermeiros, psicólogos e outros) para tratamento do câncer de mama HER2-positivo. Material e Método: Foi realizada uma revisão sistemática da literatura (RSL) focada em ensaios clínicos e estudos observacionais, utilizando PubMed (MEDLINE), Biblioteca Cochrane, Biblioteca Virtual em Saúde (BVS), Scientific Electronic Library Online (SciELO) e Literatura Latino-Americana e do Caribe em Ciências da Saúde (LILACS) com base na declaração Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA).Resultados: A RSL incluiu 5 ensaios clínicos randomizados na análise dos achados: PrefHer (NCT01401166), GAIN-2 (NCT01690702), PHranceSCa Trial (NCT03674112), MetaspHer (NCT01810393) e ChangHER (NCT01875367). Como tendência observada, os estudos relataram que pacientes e OS preferem a via de administração SC à via IV. Os principais motivos apontados pelos estudos para justificar a preferência pela a via de administração SC incluem economia de tempo, menos dor, desconforto e efeitos colaterais; promovendo benefício no volume de trabalho da equipe, reduzindo desperdício, possibilitando menores tempos de infusão e observação nas doses de ataque e de manutenção, gerando redução significativa do tempo de cadeira. Os PS concordaram que a via de administração SC economiza tempo de preparação e administração exigindo menos recursos para o preparo. Discussão e Conclusões: É possível demonstrar que há uma tendência a favor da administração SC em todas as publicações. A via de administração SC demonstrou oferecer benefícios tanto para os pacientes quanto para os profissionais de saúde. Esses dados devem fornecer evidências de suporte para uma mudança na prática em relação à administração da terapia anti-HER2, independentemente do cenário de doença - inicial ou metastático.

AbstractBackground Polypharmacy in older adults with cancer receiving chemotherapy leads to increased risks of drug interactions, translating in potential hazardous health outcomes. This study aims to assess the prevalence of polypharmacy, drug–drug interactions (DDIs), and severe-drug interactions (SDIs) in older patients with cancer. Antineoplastic agents (ANAs) involvement and possible risk contexts (comorbidities with cardiac risk, and high-risk medications) were also analysed. Methods Observational study with older adults (≥ 65 years) diagnosed with cancer, who were treated with antineoplastic agents (ANAs); it was conducted in three hospitals from the north of Portugal. Data collection was obtained using self-reports and medical records. DDIs were identified and classified using Micromedex® software. Descriptive and association analyze statistics were performed. Statistical hypothesis tests with p value less than 0.05 were considered significant. All statistical procedures and analysis were performed with R version 4.1.3. Results We enrolled 552 patients. Polypharmacy prevalence was 88.40%; 76.45% and 56.16% of the patients presented with DDIs and SDIs, respectively. SDIs with ANAs were identified in 21.20% of the patients. High-risk medications were associated with a higher risk of polypharmacy, DDIs, and SDIs. Polypharmacy and DDIs were higher in patients with hypertension or diabetes. SDIs were higher in patients with diabetes. Conclusion Polypharmacy, potential DDIs and SDIs were highly prevalent in older adults with cancer. A careful review of the medication administered is necessary to decrease it. These findings warrant further research to optimize medication in this population and decrease problems related to medication, that may lead to emergency room visits and hospitalisations, compromising patient safety and/or ongoing treatments.

Research in the field of maternal-fetal medicine brings a new approach, by involving several fields: genetics, informatics, teratology, imaging, obstetric diagnosis, maternal-fetal physiology, endocrinology, and aims to determine the relationships that appear between the maternal medical pathology and the fetal one. In this article, we present an application for monitoring and calculating risk in Trisomy-21 for pregnant women. To calculate the risk, we used 2 methods, one mathematical and one using neural networks to investigate which one offers higher precision. Following the experimental results, due to the use of several variables that increase the risk for Trisomy-21, the conclusion is that the method using neural networks is better, having an accuracy of 95%.

Anti-amyloid-β (Aβ) monoclonal antibodies (mAbs) offer the promise of disease modification and are emerging treatment options in Alzheimer's disease. Anti-Aβ mAbs require brain magnetic resonance imaging (MRI) examinations to detect anti-amyloid-induced amyloid-related imaging abnormalities (ARIA), important adverse drug reactions associated with some anti-Aβ mAbs currently available in the United States and in clinical development. We present a simple rating system for ARIA-edema (ARIA-E) that can assess severity on a 3- or 5-point scale based upon a single linear measurement of the largest area of lesion, and dissemination in space, termed the 3-point Severity Scale of ARIA-E (SSAE-3) and the 5-point Severity Scale of ARIA-E (SSAE-5), respectively. MRI results were collected from 75 participants from the SCarlet RoAD (NCT01224106) and Marguerite RoAD (NCT02051608) studies of gantenerumab. Three neuroradiologists experienced with the detection of ARIA-E were selected to read all cases independently. One rater was then chosen for a second read to assess intra-reader reproducibility. The three raters had high agreement in identifying and grading ARIA-E. The Cohen/Fleiss kappa (κ) scores (95% confidence interval [CI]) for the inter- and intra-reader comparisons for SSAE-3 and SSAE-5 were 0.79 (0.70-1.00), 0.94 (0.94-1.00), 0.73 (0.66-1.00), and 0.90 (0.90-1.00), respectively. Our study suggests that SSAE-3 and SSAE-5 are valid ARIA-E rating scales for use in routine clinical practice by experienced radiologists in specialized settings. The application of these scales in everyday use in clinical practice will support the expansion of anti-Aβ mAbs as a treatment option for people living with Alzheimer's disease. A simple rating scale is needed to rate severity of amyloid-related imaging abnormalities-edema (ARIA-E) in both research and clinical settings.The 3- and 5-point Severity Scales of ARIA-E (SSAE-3/-5) have good inter- and intra-reader agreement.The SSAE-3/-5 have been used in most major Alzheimer's disease (AD) trials to date and are suitable for large-scale use in routine clinical practice, which may help support the expansion of anti-amyloid antibodies as treatment options for AD.