The Saudi Critical Care Society practice guidelines on the management of COVID-19 in the ICU: Therapy section

BACKGROUND: The rapid increase in coronavirus disease 2019 (COVID-19) cases during the subsequent waves in Saudi Arabia and other countries prompted the Saudi Critical Care Society (SCCS) to put together a panel of experts to issue evidence-based recommendations for the management of COVID-19 in the intensive care unit (ICU). METHODS: The SCCS COVID-19 panel included 51 experts with expertise in critical care, respirology, infectious disease, epidemiology, emergency medicine, clinical pharmacy, nursing, respiratory therapy, methodology, and health policy. All members completed an electronic conflict of interest disclosure form. The panel addressed 9 questions that are related to the therapy of COVID-19 in the ICU. We identified relevant systematic reviews and clinical trials, then used the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach as well as the evidence-to-decision framework (EtD) to assess the quality of evidence and generate recommendations. RESULTS: The SCCS COVID-19 panel issued 12 recommendations on pharmacotherapeutic interventions (immunomodulators, antiviral agents, and anticoagulants) for severe and critical COVID-19, of which 3 were strong recommendations and 9 were weak recommendations. CONCLUSION: The SCCS COVID-19 panel used the GRADE approach to formulate recommendations on therapy for COVID-19 in the ICU. The EtD framework allows adaptation of these recommendations in different contexts. The SCCS guideline committee will update recommendations as new evidence becomes available

Effects of Nutrient Intake on Diagnostic Measures of Sarcopenia among Arab Men: A Cross-Sectional Study

Sarcopenia is a major public health condition and is, therefore, of great clinical interest. However, the role of nutrient intake in sarcopenia is unclear. We examined the associations between nutrient intake and diagnostic measures of sarcopenia, including low muscle mass (appendicular lean mass (ALM) divided by height squared, ALM/h2) and strength (hand-grip strength, HGS) among Arab men. This cross-sectional study included 441 men aged 46.8 ± 15.98 years. Habitual nutrient intake was assessed using a food frequency questionnaire (FFQ). Participants were classified according to different ALM/h2 and HGS reference values. Participants with normal muscle mass, defined by an ALM/h2 cutoff of <8.68 kg/m2 (−1 standard deviation (SD) <reference values Arab men), had greater daily energy, protein and fat intake, and percentage of energy from protein and fat (p < 0.01). Conversely, normal muscle mass was associated with a lower percentage of energy from carbohydrates (CHO) (p < 0.001). Regarding muscle strength, participants with HGS above 42 kg (median HGS of Arab men) had higher daily energy and protein and fat intake, but a lower percentage of energy from CHO and a lower intake of total omega-3 fatty acids (p < 0.05). Individuals with normal muscle mass and high HGS have greater daily energy, protein, and fat intake and a lower percentage of energy from CHO compared to sarcopenic individuals

The Anti-Rheumatic Drug, Leflunomide, Induces Nephrotoxicity in Mice via Upregulation of TGFβ-Mediated p53/Smad2/3 Signaling

Recent studies indicated renal toxicity and interstitial nephritis in patients receiving leflunomide (LEFN), but the exact mechanism is still unknown. The transforming growth factor β (TGFβ)/p53/Smad2/3 pathway crucially mediates renal fibrosis. We aimed to assess the nephrotoxic effect of LEFN in mice and the possible role of TGFβ-stimulated p53/SMAD2/3 signaling. The study design involved distributing sixty male albino mice into four groups: (i) vehicle-treated mice, (ii) LEFN (2.5 mg/kg), (iii) LEFN (5 mg/kg), and (iv) LEFN (10 mg/kg). The drug was given orally every 48 h and continued for 8 weeks. Blood samples were then taken from mice for the determination of kidney function parameters. Right kidneys were used for histopathologic staining and immunohistochemistry, whereas left kidneys were frozen and used for Western blot analysis of the target proteins, p-p53 and Smad2/3. Results indicated that chronic administration of LEFN in mice resulted in a four- and nine-fold increase in serum urea and creatinine levels, respectively. Kidney specimens stained with hematoxylin and eosin or periodic acid–Schiff showed significant histopathological manifestations, such as cellular irregularity, interstitial congestion, and moderate lymphocytic inflammatory infiltrate in mice treated with LEFN. Western blotting indicated upregulation of the p-p53/Smad2/3 proteins. LEFN, especially in the highest dose (10 mg/kg), produced prominent nephrotoxicity in mice. This toxicity is mediated through stimulating fibrotic changes through TGFβ-stimulated p53/Smad2/3 signaling and induction of glomerular and tubular apoptosis. An improved understanding of LEFN-induced nephrotoxicity would have great implications in the prediction, prevention, and management of leflunomide-treated rheumatic patients, and may warrant further clinical studies for following up these toxidromes