Association between different corticosteroid regimens used in severe SARS-CoV-2 infection and short-term mortality: retrospective cohort study.

INTRODUCTION: During the SARS-CoV-2 pandemic, several corticosteroid regimens have been used in the treatment of the disease, with disparate results according to drug and regimen used. For this reason, we wanted to analyze differences in early mortality derived from the use of different regimens of dexamethasone and methylprednisolone in SARS-CoV-2 infection in critically ill patients requiring admission to an ICU. METHOD: Observational, analytical and retrospective study, in an intensive care unit of a third-level university hospital, (March 2020 and June 2021). Adult patients (>18 years old) who were admitted consecutively for proven SARS-CoV-2 infection were included. The association with mortality in ICU at 28 days, different corticosteroid regimens used, was analyzed using a Cox proportional risk regression model. RESULTS: Data from a cohort of 539 patients were studied. Patient age (RR: 1.06; 95% CI: 1.02-1.10; P=<0.01) showed a significant association with 28-day mortality in the ICU. In the comparison of the different corticosteroid regimens analyzed, taking as a reference those patients who did not receive corticosteroid treatment, the dose of dexamethasone of 6mg/day showed a clear trend towards statistical significance as a protector of mortality at 28 days in the ICU (RR: 0.40, 95% CI: 0.15-1.02, p=0.05). The dose of dexamethasone of 6mg/day and low doses of methylprednisolone show a similar association with survival at 28 days (OR: 1.19; 95% CI: 0.63-2.26). CONCLUSIONS: The use of corticosteroids has been associated with better mortality outcomes in severe cases of SARS-CoV-2 infection. However, the therapeutic benefits of corticosteroids are not limited to dexamethasone alone.

The Oral Archaeome: A Scoping Review.

The Archaea domain was recognized as a separate phylogenetic lineage in the tree of life nearly 3 decades ago. It is now known as part of the human microbiome; however, given that its roles in oral sites are still poorly understood, this review aimed to establish the current level of evidence regarding archaea in the oral cavity to guide future research, providing insights on the present knowledge about the human oral archaeome. A scoping review was conducted with the PRISMA Extension for Scoping Reviews checklist. Five electronic databases were searched, as well as gray literature. Two independent reviewers performed the selection and characterization of the studies. Clinical studies were included when the target population consisted of humans of any age who were donors of samples from the oral cavity. A qualitative analysis was performed, based on the type of oral site and by considering the methods employed for archaeal identification and taxonomy, including the DNA extraction protocols, primers, and probes used. Fifty articles were included in the final scoping review, published from 1987 to 2019. Most studies sampled periodontal sites. Methanogens were the most abundant archaea in those sites, and their presence could be associated with other periodontal pathogens. No consistent relationship with different disease conditions was observed in studies that evaluated the microbiota surviving in endodontic sites. Few articles analyzed the presence of archaea in dental caries, saliva, or tongue microbiota, as well as in archaeologic samples, also showing a relationship with healthy microbiota. Archaea have been detected in different oral niches of individuals from diverse geographic locations and clinical conditions, suggesting potential roles in oral diseases. Methodological limitations may hamper our current knowledge about archaeal diversity and prevalence in oral samples, and future research with diversified methodological approaches may lead to a better comprehension of the human oral archaeome.

Acute actions and novel targets of matrix metalloproteinases in the heart and vasculature.

Matrix metalloproteinases (MMPs) have been shown to play significant roles in a number of physiological as well as pathological processes. Best known to proteolyse components of the extracellular matrix, MMPs have recently been discovered to also target a growing list of proteins apart from these, both inside and outside the cell. MMPs have also been traditionally thought of as enzymes involved in chronic processes such as angiogenesis, remodelling and atherosclerosis on a days-week time-scale. However they are now understood to also act acutely in response to oxidative stress on a minutes time-scale on non-extracellular matrix substrates. This review focuses on the acute actions and both extracellular and intracellular targets of two prominent MMP family members, MMP-2 and -9, in cardiovascular diseases including ischaemia/reperfusion injury, inflammatory heart disease, septic shock and pre-eclampsia. Also discussed are various ways of regulating MMP activity, including post-translational mechanisms, the endogenous tissue inhibitors of metalloproteinases and pharmacological inhibitors. A comprehensive understanding of MMP biology is necessary for the development of novel pharmacological therapies to combat the impact of cardiovascular disease.

Caveolin-1 inhibits matrix metalloproteinase-2 activity in the heart.

Apart from its ability to degrade extracellular matrix proteins, matrix metalloproteinase-2 (MMP-2) was recently revealed to have targets and actions within the cardiac myocyte. The localization of MMP-2 in caveolae of endothelial cells suggests that caveolin-1 (Cav-1) may play a role in regulating MMP-2. The caveolin scaffolding domain (CSD) of Cav-1 regulates several proteins including those involved with signaling cascades. Whether Cav-1 is responsible for regulating MMP-2 in the heart is unknown. Hearts from Cav-1(-/-) or Cav-1(+/+) mice were isolated and heart extracts or lipid raft enriched membrane fractions were prepared. MMP-2 activity in Cav-1(-/-) hearts was markedly enhanced when compared with Cav-1(+/+) hearts with no changes in MMP-2 protein levels between groups. In contrast, MMP-2 activity and protein level were greatly reduced in lipid raft enriched fractions of Cav-1(-/-) hearts. Purified CSD inhibited MMP-2 activity in a concentration-dependent manner as assessed using an in vitro degradation assay with a fluorogenic MMP-2 substrate (OmniMMP). These data suggest that Cav-1 plays a role in regulating MMP-2 activity. Cav-1 may thus be a novel mechanism to regulate MMP-2 activity in the heart.

Edema agudo de pulmón intraparto debido a transposición corregida de las grandes arterias o L-transposición o doble discordancia / Intrapartum acute lung edema due to corrected trasposition of the great vessels (L-transposition or doublediscordance)

Dentro de las causas de edema agudo de pulmón (EAP) durante el embarazo y parto se encuentran: la tocolisis, la sobrecarga hídrica, las cardiopatías maternas y los estados hipertensivos del embarazo. Se expone un caso de transposición corregida de los grandes vasos o transposición corregida genéticamente o L-transposición (L-TGV) no diagnosticada que se complicó con un EAP en el puerperio inmediato (AU)

Among the causes of acute lung edema during pregnancy and labor are uterolysis, water overload, maternal heart disease, and hypertensive status in pregnancy. We report a case of undiagnosed corrected transposition of the great vessels (congenitally corrected transposition or L-transposition), complicated by acute lung edema in the early puerperium (AU)

Matrix metalloproteinases contribute to endotoxin and interleukin-1beta induced vascular dysfunction.

BACKGROUND AND PURPOSE: The acute vascular inflammatory dysfunction associated with endotoxaemia may reflect an imbalance between matrix metalloproteinases (MMPs) and their natural inhibitors (TIMPs), induced by the endotoxin. This possibility was tested in rat aortic tissue. EXPERIMENTAL APPROACHES: Tone induced by phenylephrine in aortic rings was measured after exposure in vitro to ambient lipopolysaccharide (LPS) or the proinflammatory cytokine interleukin-1beta (IL-1beta) for 6h, with or without MMP inhibitors (doxycycline or GM6001). Gelatinase and MMP activities, TIMP proteins and contractility were measured in aortae taken from rats 6h after receiving LPS in vivo. KEY RESULTS: Inhibition of MMP prevented the loss of phenylephrine-induced tone in aortic rings after LPS or IL-1beta. IL-1beta also increased release of MMP-2 activity from aortic tissue. In aortae exposed in vivo to LPS, net gelatinase, MMP-9 activities and TIMP-1 protein levels were increased, whereas TIMP-4 was reduced. These aortae were hypocontractile to both phenylephrine and KCl. Hypocontractility was partially reversed by doxycycline ex vivo. CONCLUSIONS AND IMPLICATIONS: MMP inhibitors ameliorate vascular hyporeactivity induced by either LPS or IL-1beta in vitro. LPS in vivo alters the balance between MMPs and TIMPs, contributing to vascular dysfunction which is partially reversed by MMP inhibitors. Vascular MMPs are activated as a result of LPS or IL-1beta-induced stress and contribute to the hyporeactivity of blood vessels to vasoconstrictors.

Aleutian mink disease parvovirus in wild riparian carnivores in Spain.

Serious declines in populations of native European mink (Mustela lutreola) have occurred in Europe. One responsible factor may be infectious diseases introduced by exotic American mink (Mustela vison). In order to investigate a possible role for Aleutian mink disease parvovirus (ADV), we surveyed native riparian carnivores and feral American mink. When serum samples from 12 free-ranging European and 16 feral American mink were tested, antibodies to ADV were detected from three of nine European mink. ADV DNA was detected by polymerase chain reaction in whole cell DNA from four of seven carcasses; two American mink, one European mink and a Eurasian otter (Lutra lutra). Lesions typical of Aleutian disease were present in one of the American mink. A portion of the ADV VP2 capsid gene was sequenced and the results suggested that two sequence types of ADV were circulating in Spain, and that the Spanish ADVs differed from other described isolates from North America and Europe. Future conservation and restoration efforts should include measures to avoid introduction or spread of ADV infection to native animals.