The mono-carboxypeptidase Angiotensin-Converting Enzyme 2 (ACE2) is an important player of the renin-angiotensin system (RAS). ACE2 is also the receptor for SARS-CoV-2, the new coronavirus that causes COVID-19. It has been hypothesized that following SARS-CoV-2/ACE2 internalization Ang II level would increase in parallel to a decrease of Ang-(1-7) in COVID-19 patients. In this preliminary report, we analyzed the plasma levels of angiotensin peptides in 19 severe COVID-19 patients and 19 non-COVID-19 volunteers. Unexpectedly, a significant increase in circulating Ang-(1-7) and lower Ang II plasma level were found in critically ill COVID-19 patients. Accordingly, an increased Ang-(1-7)/ Ang II ratio was observed in COVID-19 suggesting a RAS dysregulation toward an increased formation of Ang-(1-7) in these patients.

The monocarboxypeptidase angiotensin-converting enzyme 2 (ACE2) is a major player in the the renin–angiotensin system (RAS) as it converts the decapeptide angiotensin (Ang) I to Ang-(1–9) and Ang II to Ang-(1–7) (figure 1a) [1]. ACE2 is also a target for the new human coronavirus SARS-CoV-2, which is responsible for the dramatic ongoing COVID-19 pandemic [2]. It has been suggested that following SARS-CoV-2/ACE2 internalisation, Ang II level increases [3] in parallel to a decrease of Ang-(1–7) level [4]. These changes would be expected both at tissue and circulatory levels. Considering that Ang-(1–7) has many beneficial effects, including anti-inflammatory, antithrombogenic and antifibrotic activities [1], it has been hypothesised that Ang-(1–7) administration would improve the clinical outcome of COVID-19 patients. Aiming to test this hypothesis, a phase I/II clinical trial (www.clinicaltrials.gov identifier NCT04633772) has been initiated with a planned phase III clinical trial (NCT04332666).

A 75-year-old man was hospitalised for bronchoscopy with biopsy due to a suspicious pulmonary mass at chest tomography. He had significant dyspnoea, constipation, nausea, vomiting, anorexia and a 33% loss of weight in the past 3 months. Biopsy revealed a pulmonary squamous cell carcinoma, which was inoperable. Tramadol used at home for 3 months was replaced by morphine on admission. The patient remained constipated despite prokinetics and laxatives, leading to the diagnostic hypothesis of paraneoplastic motility disorder and opioid-induced constipation. Abdominal tomography ruled out the possibility of mechanical obstruction. As complications, the patient presented superior vena cava syndrome and opioid (morphine) intoxication. The patient died a few days later. The management of this case highlights the importance of multidisciplinary care and the challenges of palliative oncology care. Paraneoplastic motility disorder must always be considered among the mechanisms of intestinal dysfunction in patients with advanced oncological disease.

Objetiva-se avaliar as evidências acerca do perfil de segurança para idosos dos medicamentos utili-zados no tratamentodo Diabetes Mellitus tipo 2, que são considerados medicamentos potencialmen-te inadequados pelo critério de Beers epela ferramenta STOPP: glibenclamida e clorpropamida. Realizou-se uma revisão integrativa da literatura realizada a partirda base de dados PubMed. Foram utilizados os descritores do banco Medical Subject Headings (MeSH) “chlorpropamide”,“glyburide” e “sulfonylureas” combinados ao descritor “aged”. Foram incluídos artigos que avaliaram o perfil de segurança douso de clorpropamida e/ou glibenclamida por idosos. Sete artigos foram selecionados. Não foi encontrado nenhum estudoque avaliasse a clorpropamida. Dois estudos avaliaram a segu-rança cardiovascular e o risco de morte com glibenclamida,mas não foram apontadas diferenças entre o uso deste medicamento e de outros da classe das sulfonilureias. Os demaistrabalhos eviden-ciaram uma associação entre o uso de glibenclamida e hipoglicemia, apesar de apresentarem resultados conflitantes quanto à relação da ocorrência deste evento com a função renal dos pacientes ido-sos. Concluí-se quea literatura aponta a necessidade de reavaliação da prescrição de glibenclamida, dada sua comprovada relação com odesenvolvimento de hipoglicemia em pacientes idosos.Palavras-chave: Diabetes Mellitus; Idoso; Glibenclamida; Clorpropamida; Efeitos Adversos. ABSTRACTThe aim is to evaluate scientific evidences about the safety profile among older patients of drugs used to treat type2 Diabetes that are considered potentially inappropriate medications by the Beers criteria and STOPP: glyburideand chlorpropamide. An integrative review was performed on Pub-Med database using Medical Subject Headings(MeSH), using the descriptors: “chlorpropamide”, “glyburide”, “sulfonylureas” and “aged”. Articles that evaluated thesafety profile of chlorpropamide and/or glyburide for older patients were included. Seven articles were selected,none of which as-sessed the safety profile of chlorpropamide. Two studies evaluated the cardiovascular safety andthe risk of death with glyburide, but no difference between this product and other drugs from the sul-fonylureasclass was identified. The other studies showed an association between the use of gly-buride and hypoglycemia,despite showing conflicting results regarding the relationship between this event and renal function of olderpatients. It concludes that the scientific literature showed the needing for reassessment of glyburide prescriptionamong older patients, given its proven relation-ship with the occurrence of hypoglycemia.Keywords: Diabetes Mellitus; Aged; Glyburide; Chlorpropamide; Adverse Effects.

doi: medRxiv preprint NOTE: This preprint reports new research that has not been certified by peer review and should not be used to guide clinical practice.