COVID-19-associated cerebral microbleeds in the general population.

Cerebral microbleeds are frequent incidental findings on brain MRI and have previously been shown to occur in Coronavirus Disease 2019 (COVID-19) cohorts of critically ill patients. We aimed to determine the risk of having microbleeds on medically indicated brain MRI and compare non-hospitalized COVID-19-infected patients with non-infected controls. In this retrospective case-control study, we included patients over 18 years of age, having an MRI with a susceptibility-weighted sequence, between 1 January 2019 and 1 July 2021. Cases were identified based on a positive reverse transcriptase polymerase chain reaction test for SARS-CoV-2 and matched with three non-exposed controls, based on age, sex, body mass index and comorbidities. The number of cerebral microbleeds on each scan was determined using artificial intelligence. We included 73 cases and 219 matched non-exposed controls. COVID-19 was associated with significantly greater odds of having cerebral microbleeds on MRI [odds ratio 2.66 (1.23-5.76, 95% confidence interval)], increasingly so when patients with dementia and hospitalized patients were excluded. Our findings indicate that cerebral microbleeds may be associated with COVID-19 infections. This finding may add to the pathophysiological considerations of cerebral microbleeds and help explain cases of incidental cerebral microbleeds in patients with previous COVID-19.

Deep Learning to Detect Pancreatic Cystic Lesions on Abdominal Computed Tomography Scans: Development and Validation Study.

BACKGROUND: Pancreatic cystic lesions (PCLs) are frequent and underreported incidental findings on computed tomography (CT) scans and can evolve to pancreatic cancer-the most lethal cancer, with less than 5 months of life expectancy. OBJECTIVE: The aim of this study was to develop and validate an artificial deep neural network (attention gate U-Net, also named "AGNet") for automated detection of PCLs. This kind of technology can help radiologists to cope with an increasing demand of cross-sectional imaging tests and increase the number of PCLs incidentally detected, thus increasing the early detection of pancreatic cancer. METHODS: We adapted and evaluated an algorithm based on an attention gate U-Net architecture for automated detection of PCL on CTs. A total of 335 abdominal CTs with PCLs and control cases were manually segmented in 3D by 2 radiologists with over 10 years of experience in consensus with a board-certified radiologist specialized in abdominal radiology. This information was used to train a neural network for segmentation followed by a postprocessing pipeline that filtered the results of the network and applied some physical constraints, such as the expected position of the pancreas, to minimize the number of false positives. RESULTS: Of 335 studies included in this study, 297 had a PCL, including serous cystadenoma, intraductal pseudopapillary mucinous neoplasia, mucinous cystic neoplasm, and pseudocysts . The Shannon Index of the chosen data set was 0.991 with an evenness of 0.902. The mean sensitivity obtained in the detection of these lesions was 93.1% (SD 0.1%), and the specificity was 81.8% (SD 0.1%). CONCLUSIONS: This study shows a good performance of an automated artificial deep neural network in the detection of PCL on both noncontrast- and contrast-enhanced abdominal CT scans.

Pre-operative ribociclib plus letrozole versus chemotherapy: Health-related quality of life outcomes from the SOLTI CORALLEEN trial.

INTRODUCTION: In the phase II CORALLEEN trial, patients with PAM50 luminal B early breast cancer (EBC) were randomised to neoadjuvant ribociclib plus letrozole (R + L) or chemotherapy based on anthracyclines and taxanes. Results from the primary efficacy analysis showed a similar proportion of patients with response at surgery in both groups. How health-related quality of life (HRQoL) outcomes with R + L compare with chemotherapy in EBC setting is still unknown. Here, we report the results of the HRQoL analysis from the CORALLEEN study. METHODS: A total of 106 women were randomised 1:1 to receive neoadjuvant R + L (n = 52) or chemotherapy (n = 54). Patient-reported outcomes were assessed using two questionnaires: EORTC QLQ-C30 and EORTC QLQ-BR23. Change from baseline in the global health status, functional, and symptom scales was analysed using linear mixed-effect models, and between-treatment differences were estimated along with 95% confidence interval (95% CI). RESULTS: At baseline, the overall questionnaire available rate was 94.3%, and patient-reported outcomes were similar between treatment groups. At the end of the study treatment (24 weeks), patients receiving R + L showed better global health status scores with a between-treatment difference of 17.7 points (95% CI 9.2-26.2; p-value <0.001). The R + L group also presented numerically better outcomes in all functional and symptom scales. The larger between-treatment differences in symptom severity were found in fatigue (-28.9; 95% CI -38.5 to -19.3), appetite loss (-23; 95% CI -34.9 to -11.2) and systematic therapy side-effects (-11.4; 95% CI -18.3 to -4.6). CONCLUSIONS: Neoadjuvant R + L was associated with better HRQoL outcomes compared with chemotherapy in patients with luminal B EBC. REGISTRATION IDENTIFICATION: ClinicalTrials.gov Identifier: NCT03248427.

GDF15 and ACE2 stratify COVID-19 patients according to severity while ACE2 mutations increase infection susceptibility.

Coronavirus disease 19 (COVID-19) is a persistent global pandemic with a very heterogeneous disease presentation ranging from a mild disease to dismal prognosis. Early detection of sensitivity and severity of COVID-19 is essential for the development of new treatments. In the present study, we measured the levels of circulating growth differentiation factor 15 (GDF15) and angiotensin-converting enzyme 2 (ACE2) in plasma of severity-stratified COVID-19 patients and uninfected control patients and characterized the in vitro effects and cohort frequency of ACE2 SNPs. Our results show that while circulating GDF15 and ACE2 stratify COVID-19 patients according to disease severity, ACE2 missense SNPs constitute a risk factor linked to infection susceptibility.

Ribociclib plus letrozole versus chemotherapy for postmenopausal women with hormone receptor-positive, HER2-negative, luminal B breast cancer (CORALLEEN): an open-label, multicentre, randomised, phase 2 trial.

BACKGROUND: In hormone receptor-positive, HER2-negative early stage breast cancer, cyclin-dependent kinases 4 and 6 (CDK4/6) inhibition in combination with endocrine therapy could represent an alternative to multiagent chemotherapy. We aimed to evaluate the biological and clinical activity of neoadjuvant ribociclib plus letrozole in the luminal B subtype of early stage breast cancer. METHODS: CORALLEEN is a parallel-arm, multicentre, randomised, open-label, phase 2 trial completed across 21 hospitals in Spain. We recruited postmenopausal women (≥18 years) with stage I-IIIA hormone receptor-positive, Eastern Cooperative Oncology Group Performance Status 0-1, HER2-negative breast cancer and luminal B by PAM50 with histologically confirmed, operable primary tumour size of at least 2 cm in diameter as measured by MRI. Patients were randomly assigned (1:1) using a web-based system and permuted blocks of 25 to receive either six 28-days cycles of ribociclib (oral 600 mg once daily for 3 weeks on, 1 week off) plus daily letrozole (oral 2·5 mg/day) or four cycles of doxorubicin (intravenous 60 mg/m2) and cyclophosphamide (intravenous 600 mg/m2) every 21 days followed by weekly paclitaxel (intravenous 80 mg/m2) for 12 weeks. The total duration of the neoadjuvant therapy was 24 weeks. Randomisation was stratified by tumour size and nodal involvement. Samples were prospectively collected at baseline (day 0), day 15, and surgery. The primary endpoint was to evaluate the proportion of patients with PAM50 low-risk-of-relapse (ROR) disease at surgery in the modified intention-to-treat population including all randomly assigned patients who received study drug and had a baseline and at least one post-baseline measurement of ROR score. The PAM50 ROR risk class integrated gene expression data, tumour size, and nodal status to define prognosis. This trial was registered at ClinicalTrials.gov, NCT03248427. FINDINGS: Between July 27, 2017 to Dec 7, 2018, 106 patients were enrolled. At baseline, of the 106 patients, 92 (87%) patients had high ROR disease (44 [85%] of 52 in the ribociclib and letrozole group and 48 [89%] of 54 in the chemotherapy group) and 14 (13%) patients had intermediate-ROR disease (eight [15%] and six [11%]). Median follow-up was 200·0 days (IQR 191·2-206·0). At surgery, 23 (46·9%; 95% CI 32·5-61·7) of 49 patients in the ribociclib plus letrozole group and 24 (46·1%; 32·9-61·5) of 52 patients in the chemotherapy group were low-ROR. The most common grade 3-4 adverse events in the ribociclib plus letrozole group were neutropenia (22 [43%] of 51 patients) and elevated alanine aminotransferase concentrations (ten [20%]). The most common grade 3-4 adverse events in the chemotherapy group were neutropenia (31 [60%] of 52 patients) and febrile neutropenia (seven [13%]). No deaths were observed during the study in either group. INTERPRETATION: Our results suggest that some patients with high-risk, early stage, hormone receptor-positive, HER2-negative breast cancer could achieve molecular downstaging of their disease with CDK4/6 inhibitor and endocrine therapy. FUNDING: Novartis, Nanostring, Breast Cancer Research Foundation-AACR Career Development Award.

Salud comunitaria confinada: reflexiones y experiencias desde la salud pública local / Confined community health: reflections and experiences from the local public health

Este artículo pretende compartir las reflexiones sobre la acción comunitaria en que la Agència de Salut Pública de Barcelona ha estado involucrada en la emergencia de COVID-19. El trabajo realizado puede ordenarse en tres etapas, frecuentemente solapadas: detectar necesidades o problemas, e informar; contactar con las personas participantes y agentes territoriales para valorar qué hacer y cómo hacerlo; y adaptar las intervenciones a la "nueva normalidad" y generar respuestas con los activos comunitarios a las necesidades detectadas. Los problemas emergentes incluyeron: no poder realizar el confinamiento (por falta de casa, condiciones materiales, vivir en situación de violencia); brecha digital (falta de conocimientos, dispositivos, acceso a Wifi); mayor exposición al COVID-19 en los trabajos esenciales pero precarizados, feminizados y racializados (cuidados, limpieza, alimentación), frecuentes en los barrios en que trabajamos; barreras idiomáticas y culturales para seguir las recomendaciones; pérdida de empleo; ingresos insuficientes para cubrir necesidades básicas; dificultades de conciliación; aislamiento social; y deterioro de la salud emocional provocado por la situación. Durante el proceso, algunas intervenciones se adaptaron para continuar de forma telemática, y se intentaron cubrir las necesidades primarias sobre conocimientos y dispositivos de algunas personas participantes a través de las redes solidarias y recursos existentes. La acción comunitaria en salud, desde una mirada crítica, interseccional y local, mediante trabajo intersectorial y la participación de la comunidad, puede contribuir a: facilitar una respuesta adaptada al contexto en caso de crisis sanitaria y mitigar los efectos derivados de esta crisis económica y social

This paper aims to share the reflections related to the community actions in which the Agència de Salut Pública de Barcelona has been involved during the emergency of COVID-19. The tasks carried out can be arranged in three stages, frequently overlapping: detection of needs and problems; contact with key stakeholders to assess what to do and how to do it; adaptation of the interventions to the "new normal" and generation of new responses. The emerging problems included: not being able to do the confinement (due to homelessness, material conditions, living in a situation of violence); digital gap (lack of knowledge, devices, access to Wifi); greater exposure to COVID-19 in the essential but precarious, feminized and racialized jobs (care, cleaning, food shops) that are the most frequent in the neighborhoods in where we work; language and cultural barriers that preclude to follow recommendations; to lose employment; insufficient income to cover basic needs; social isolation; and the deterioration of emotional health caused by the situation. During the process, some interventions were adapted to be delivered on-line. Solidarity networks and local resources were key to meet basic needs, but also other needs related to lack of digital knowledge or device. Community action in health, from a critical, intersectional and local perspective, and with intersectoral work and community participation, can contribute to: facilitate a contextualized response in the event of a health crisis; mitigate the effects derived from its economic and social crisis