Evaluation of urinary cysteinyl leukotrienes as biomarkers of severity and putative therapeutic targets in COVID-19 patients.

BACKGROUND: Cysteinyl leukotrienes (CysLT) are potent inflammation-promoting mediators, but remain scarcely explored in COVID-19. We evaluated urinary CysLT (U-CysLT) relationship with disease severity and their usefulness for prognostication in hospitalized COVID-19 patients. The impact on U-CysLT of veno-venous extracorporeal membrane oxygenation (VV-ECMO) and of comorbidities such as hypertension and obesity was also assessed. METHODS: Blood and spot urine were collected in "severe" (n = 26), "critically ill" (n = 17) and "critically ill on VV-ECMO" (n = 17) patients with COVID-19 at days 1-2 (admission), 3-4, 5-8 and weekly thereafter, and in controls (n = 23) at a single time point. U-CysLT were measured by ELISA. Routine markers, prognostic scores and outcomes were also evaluated. RESULTS: U-CysLT did not differ between groups at admission, but significantly increased along hospitalization only in critical groups, being markedly higher in VV-ECMO patients, especially in hypertensives. U-CysLT values during the first week were positively associated with ICU and total hospital length of stay in critical groups and showed acceptable area under curve (AUC) for prediction of 30-day mortality (AUC: 0.734, p = 0.001) among all patients. CONCLUSIONS: U-CysLT increase during hospitalization in critical COVID-19 patients, especially in hypertensives on VV-ECMO. U-CysLT association with severe outcomes suggests their usefulness for prognostication and as therapeutic targets.

Inflammatory Bowel Disease - Non-biological treatment.

Nowadays, non-biological treatments remain valuable approaches among the therapeutic armamentarium of inflammatory bowel disease (IBD). Mesalamine is the core treatment of mild­to­moderate ulcerative colitis (UC) and corticosteroids are crucial for the induction of remission of moderate­to­severe flares in both UC and Crohn's disease (CD). Even approaches as cyclosporine, tacrolimus, azathioprine, methotrexate, and surgery still have a nuclear position as strategies to induce and/or maintain remission in IBD. Due to their particularities and to the accumulated evidence, each of these strategies conquered peculiar roles in the overall IBD strategy, all of them contributing to better outcomes. This review emphasizes the particular roles that non-biological treatments gained over time: recent mesalamine formulations to increase adhesion rates, higher doses of 5-ASA for high-risk patients, MMX technology to improve drug release and attain higher bowel concentrations, cyclosporine as a bridge to vedolizumab, tacrolimus as a potential alternative to thiopurines or infliximab, azathioprine in combination therapy with infliximab and dubious in monotherapy, and surgery as a mean to a "better end".

Spontaneous reporting of adverse reactions associated with the COVID-19 vaccine in health care professionals: A descriptive observational study conducted in a Portuguese hospital.

Background: The coronavirus disease 2019 (COVID-19) was classified as a pandemic in March 2020 by the World Health Organization. The Pfizer-BioNTech COVID-19 vaccine was the first to be authorized in the European Union, based on data from phase 1, 2, and 3 clinical trials of limited duration. Concerns have been raised regarding the vaccine's safety profile. Some of the adverse drug reactions (ADRs) associated with vaccines may not have been identified during clinical trials. This study aimed to identify ADRs associated with the Pfizer-BioNTech vaccine in health care professionals at a Portuguese tertiary university hospital. Methods: The data used in this analysis consist of ADRs reported through a spontaneous notification system from vaccines administered between December 27, 2020, and January 31, 2021. ADRs were categorized according to the MedDRA terminology. Results: A total of 8,605 Pfizer-BioNTech vaccines were administered to 4568 health care professionals. ADRs were reported among 520 of the vaccines, with an incidence of 13.56% in women and 5.31% in men. The mean age of the population reporting ADRs was 41.52 years, with a standard deviation of 9.83 years. The most frequent ADRs were myalgia (n = 274), headache (n = 199), pyrexia (n = 164), injection site pain (n = 160), fatigue (n = 84), nausea (n = 81), chills (n = 65), lymphadenopathy (n = 64), and arthralgia (n = 53). Hypersensitivity reactions occurred in 15 health care professionals, with no anaphylactic reactions observed. A total of four Important Medical Events were observed, which consisted of two cases of syncope, one case of sudden hearing loss, and one case of transverse myelitis. Conclusion: The vaccine was well-tolerated among the study participants. Reactogenicity was greater after the second dose. The incidence of ADRs was higher in women and individuals aged between 40 to 49 years. Systemic adverse reactions were most frequently reported. Systematic monitoring of ADRs of COVID-19 vaccines in real-life context is essential for a more robust establishment of its safety profile.

Gut bacterial microbiome composition and statin intake-A systematic review.

Recently, the gut microbiome has become an important field of interest. Indeed, the microbiome has been associated to numerous drug interactions and it is thought to influence the efficacy of pharmacologic treatments. Although statins are widely prescribed medications, there remains considerable variability in its therapeutic response. In this context, we aimed to investigate how statins modulate the gut microbiome and, reversely, how can the microbiome influence the course of anti-hypercholesterolemic treatment. We conducted a systematic review by searching four online databases, in accordance with PRISMA guidelines. Studies addressing gut microbiome changes following statin treatment and those assessing statins' response and associating it with patients' microbiome were included. Due to the limited number of results, we decided to include studies enrolling both humans and animals. We summarized information from three human and seven animal studies and aimed to assess the influence of gut microbiome composition on statin response (Outcome 1) and to evaluate the impact of statin treatment on the gut microbiome (Outcome 2). An association between a certain microbiome composition that promoted the lipid-lowering effect of statins was found. However, what kind of microorganisms and how they can exert this effect remains uncertain. Furthermore, statins might have a role in the modulation of the gut microbiome, but then again, it is still unknown whether this change is directly caused by the drug or another metabolic mechanism. Even though gut microbiota may have several potential therapeutic implications, its use as a personalized predictive biomarker requires further studies.