Use of mNUTRIC-Score for Nutrition Risk Assessment and Prognosis Prediction in Critically Ill Patients with COVID-19: A Retrospective Observational Study.

INTRODUCTION: Nutritional risk is highly prevalent in patients with COVID-19. Relevant data on nutritional assessment in the critically ill population are scarce. This study was conducted to evaluate the modified Nutrition Risk in the Critically Ill (mNUTRIC)-Score as a mortality risk factor in mechanically ventilated patients with COVID-19. METHODS: We conducted this retrospective observational study in critically ill patients with COVID-19. Patients' characteristics and clinical information were obtained from electronic medical records. The nutritional risk for each patient was assessed at the time of mechanical ventilation using the mNUTRIC-Score. The major outcome was 28-day mortality. RESULTS: Ninety-eight patients were analyzed (mean age, 57.22 ± 13.66 years, 68.4% male); 46.9% of critically ill COVID-19 patients were categorized as being at high nutrition risk (mNUTRIC-Score of ≥5). A multivariate logistic regression model indicated that high nutritional risk has higher 28-day hospital mortality (OR = 4.206, 95% CI: 1.147-15.425, p=0.030). A multivariate Cox regression analysis showed that high-risk mNUTRIC-Score had a significantly increased full-length mortality risk during hospitalization (OR = 1.991, 95% CI: 1.219-3.252, p=0.006). CONCLUSION: The mNUTRIC-Score is an independent mortality risk factor during hospitalization in critically ill COVID-19 patients.

Multisystem Inflammatory Syndrome in Children (MIS-C) Following SARS-CoV-2 Infection: Role of Oxidative Stress.

With the appearance of the SARS-CoV-2 virus in December 2019, all countries in the world have implemented different strategies to prevent its spread and to intensively search for effective treatments. Initially, severe cases of the disease were considered in adult patients; however, cases of older school-age children and adolescents who presented fever, hypotension, severe abdominal pain and cardiac dysfunction, positive for SARS-CoV-2 infection, have been reported, with increased pro-inflammatory cytokines and tissue damage, condition denominated multisystemic inflammatory syndrome (MIS-C); The emerging data from patients with MIS-C have suggested unique characteristics in the immunological response and also clinical similarities with other inflammatory syndromes, which can support as a reference in the search for molecular mechanisms involved in MIS-C. We here in propose that oxidative stress (OE) may play a very important role in the pathophysiology of MIS-C, such as occurs in Kawasaki disease (KD), severe COVID-19 in adults and other processes with characteristics of vascular damage similar to MIS- C, for which we review the available information that can be correlated with possible redox mechanisms.

Effect of statins on oxidative DNA damage in diabetic polyneuropathy.

Oxidative stress induces nerve damage in type 2 diabetes mellitus and leads to diabetic polyneuropathy (DPN) and can affect the DNA and antioxidant status. Statins have pleiotropic, protective effects on the peripheral nerves of patients with diabetes. The aim of this study was to determine the effects of ezetimibe/simvastatin and rosuvastatin on DNA damage in patients with DPN. This randomized, double-blind, placebo-controlled, clinical trial comprised outpatients from Guadalajara, Mexico. The inclusion criteria were either gender, age 35-80 years, type 2 diabetes, glycated hemoglobin ≤10%, diabetic polyneuropathy stage 1/2, and signed informed consent. Patients who were taking antioxidant therapy or statins, had hypersensitivity to drugs, experienced organ failure, were pregnant or breastfeeding, or had other types of neuropathy were excluded. We assigned patients to placebo, ezetimibe/simvastatin 10/20 mg, or rosuvastatin 20 mg, and the primary outcomes were 8-hydroxy-2'-deoxyguanosine (8-OHdG) for DNA damage, 8-oxoguanine-DNA-N-glycosilase (hOGG1) for DNA repair, and superoxide dismutase (SOD). Seventy-four patients were recruited. Nine patients were included as negative controls. There were no differences in 8-OHdG between the healthy subjects (4.68 [3.53-6.38] ng/mL) and the DPN patients (4.51 [1.22-9.84] ng/mL), whereas the hOGG1 level was 0.39 (0.37-0.42) ng/mL in the healthy subjects and 0.41 (0.38-0.54) ng/mL in patients with DPN at baseline (p = 0.01). SOD decreased significantly in patients with DPN (5.35 [0.01-17.90] U/mL) compared with the healthy subjects (9.81 [8.66-12.61] U/mL) at baseline (p < 0.001). No significant changes in DNA biomarkers were observed in any group between baseline and final levels. We noted a rise in hOGG1 in patients with DPN, without modifications after treatment. There was a slight, albeit insignificant, increase in SOD in patients who were on statins.

Diabetic Polyneuropathy in Type 2 Diabetes Mellitus: Inflammation, Oxidative Stress, and Mitochondrial Function.

Diabetic polyneuropathy (DPN) is defined as peripheral nerve dysfunction. There are three main alterations involved in the pathologic changes of DPN: inflammation, oxidative stress, and mitochondrial dysfunction. Inflammation induces activation of nuclear factor kappa B, activator protein 1, and mitogen-activated protein kinases. Oxidative stress induced by hyperglycemia is mediated by several identified pathways: polyol, hexosamine, protein kinase C, advanced glycosylation end-products, and glycolysis. In addition, mitochondrial dysfunction accounts for most of the production of reactive oxygen and nitrosative species. These free radicals cause lipid peroxidation, protein modification, and nucleic acid damage, to finally induce axonal degeneration and segmental demyelination. The prevalence of DPN ranges from 2.4% to 78.8% worldwide, depending on the diagnostic method and the population assessed (hospital-based or outpatients). Risk factors include age, male gender, duration of diabetes, uncontrolled glycaemia, height, overweight and obesity, and insulin treatment. Several diagnostic methods have been developed, and composite scores combined with nerve conduction studies are the most reliable to identify early DPN. Treatment should be directed to improve etiologic factors besides reducing symptoms; several approaches have been evaluated to reduce neuropathic impairments and improve nerve conduction, such as oral antidiabetics, statins, and antioxidants (alpha-lipoic acid, ubiquinone, and flavonoids).

Effects of Ezetimibe/Simvastatin and Rosuvastatin on Oxidative Stress in Diabetic Neuropathy: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial.

OBJECTIVE: To evaluate the effects of ezetimibe/simvastatin (EZE/SIMV) and rosuvastatin (ROSUV) on oxidative stress (OS) markers in patients with diabetic polyneuropathy (DPN). METHODS: We performed a randomized, double-blind, placebo-controlled phase III clinical trial in adult patients with Type 2 Diabetes Mellitus (T2DM) and DPN, as evaluated by composite scores and nerve conduction studies (NCS). Seventy-four subjects with T2DM were allocated 1 : 1 : 1 to placebo, EZE/SIMV 10/20 mg, or ROSUV 20 mg for 16 weeks. All patients were assessed before and after treatment: primary outcomes were lipid peroxidation (LPO), and nitric oxide (NO) surrogate levels in plasma; secondary outcomes included NCS, neuropathic symptom scores, and metabolic parameters. Data were expressed as mean ± SD or SEM, frequencies, and percentages; we used nonparametric analysis. RESULTS: LPO levels were reduced in both statin arms after 16 weeks of treatment (p < 0.05 versus baseline), without changes in the placebo group. NO levels were not significantly affected by statin treatment, although a trend towards significance concerning increased NO levels was noted in both statin arms. No significant changes were observed for the NCS or composite scores. DISCUSSION: EZE/SIMV and ROSUV are superior to placebo in reducing LPO in subjects with T2DM suffering from polyneuropathy. This trial is registered with NCT02129231.

Sildenafil citrate diminishes microalbuminuria and the percentage of A1c in male patients with type 2 diabetes.

UNLABELLED: Sildenafil citrate has shown to display beneficial cardiovascular effects, suggesting that it may have other systemic benefits involving the endothelium. There is little data regarding the long-term use of this drug and the effects of this on different organs. OBJECTIVE: The primary aim of this study was to determine whether sildenafil citrate diminishes concentrations of microalbuminuria and percentage of A1c in patients with type 2 diabetes. DESIGN: A double-blind, randomized, controlled trial in 40 male patients, age 35-50, with type 2 diabetes. Subjects received sildenafil citrate 50 mg daily (n=20) or placebo (n=20) for 30 days. Levels of hs-CRP, microalbuminuria, homocysteine, A1c and erectile function were measured at baseline and to the end of the study. RESULTS: Men that received sildenafil citrate displayed a significant decrease in the microalbuminuria concentrations (p<0.01) versus baseline, (p=0.02) versus placebo and A1c (p<0.01) versus baseline, (p=0.01) versus placebo. In addition, we observed a significant increase in the total IIEF score after 30 days of treatment (p<0.01) versus baseline, (p<0.01) versus placebo. CONCLUSIONS: The administration of 50mg of sildenafil citrate for 30 consecutive days diminishes microalbuminuria and the percentage of A1c in patients with type 2 diabetes.