The Triglycerides and Glucose Index Is an Independent Risk Factor for Acute Respiratory Distress Syndrome in Patients with COVID-19.

Introduction: Although it has been observed that the triglycerides and glucose (TyG) index, a biomarker of insulin resistance, is associated with severity and morbidity by COVID-19, evidence is still scarce. Therefore, the objective of this study was to determine whether the TyG index is associated with both the degree of severity and mortality by acute respiratory distress syndrome (ARDS) in patients with COVID-19. Methods: Men and women aged 20 years or more with diagnosis of COVID-19 were included in a case-control study. Exclusion criteria were pregnancy, cancer, autoimmune diseases, autoimmune treatment, and incomplete data. Patients with severe COVID-19 ARDS were allocated into the case group, and those with mild or moderate COVID-19 ARDS in the control group. COVID-19 was defined by a positive reverse transcriptase-polymerase chain reaction test for SARS-CoV-2, and ARDS was defined according to the Berlin criteria. Results: A total of 206 patients were included and allocated into the case (n = 103) and control (n = 103) groups. The logistic regression analysis adjusted by age, sex, and body mass index showed that the TyG index is significantly associated with moderate [odds ratio (OR) = 6.0; 95% confidence interval (CI): 1.1-30.6] and severe (OR = 9.5; 95% CI: 2.4-37.5) COVID-19 ARDS, and death (OR = 10.1; 95% CI: 2.2-46.5). Conclusion: The results of our study show a significant and independent association of the TyG index with ARDS and mortality in patients with COVID-19.

Effect of Fibrate Treatment on Circulating Adipokine Levels: A Systematic Review and Meta-analysis of Randomized Clinical Trials.

BACKGROUND: Fibrates are widely used in the treatment of dyslipidemia and associated metabolic abnormalities; however, their effects on adipokines are unclear. AIM OF THE STUDY: This meta-analysis of clinical trials aimed to evaluate the effect of fibrates on circulating adipokine levels. METHODS: Only randomized controlled trials investigating the impact/effect of fibrate treatment on circulating adipokine levels were included from searches in PubMed-Medline, SCOPUS, ClinicalTrials.gov, Web of Science, and Google Scholar databases. A random effects model and the generic inverse variance method were used for the meta-analysis. Sensitivity analysis was conducted using the leave-one-out method. RESULTS: This meta-analysis of 22 clinical trials showed a significant reduction on/in leptin (WMD: -1.58 ng/mL, 95% CI: -2.96, -0.20, p = 0.02, I2 = 0%), plasminogen activator inhibitor-1 (PAI-1) (WMD: -13.86 ng/mL, 95% CI: -26.70, -1.03, p = 0.03, I2 = 99%), and visfatin (WMD: -1.52 ng/mL, 95% CI: -2.49, -0.56, p = 0.002, I2 = 0%) after fibrate therapy; no significant effect was observed on adiponectin (WMD: -0.69 µg/ml, 95% CI: -1.40, 0.02, p = 0.06, I2 = 83%) and resistin (WMD: -2.27 ng/mL, 95% CI: -7.11, 2.57, p = 0.36, I2 = 0%). The sensitivity analysis was robust only for visfatin, while the effect size was sensitive to one arm for leptin, four for adiponectin, and two for PAI-1. CONCLUSION: This meta-analysis showed that fibrate treatment significantly improves adipokine levels with a decrease in leptin, PAI-1, and visfatin, suggesting potential additional clinical therapeutic benefits through/of fibrate treatment on adipose tissue.

Clinical efficacy of botulinum toxin in lateral elbow tendinopathy: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Botulinum toxin injections for lateral elbow tendinopathy have been used as an alternative therapeutic option. However, few studies have quantitatively summarized the effect of botulinum toxin as well as its clinical significance. We aimed to evaluate the clinical efficacy (based on pain and grip strength) and adverse events of botulinum toxin on lateral elbow tendinopathy. PATIENTS AND METHODS: The MEDLINE, EMBASE, Web of Science, and Scopus databases were searched until March 2023 for randomized controlled trials reporting the effects of botulinum toxin injections on lateral elbow tendinopathy. A random- or fixed-effects model (depending of inter-study variability) and generic inverse variance method were used to pool quantitative data from outcomes. The risk of bias was assessed with the Cochrane Risk of Bias 2.0 tool. RESULTS: A total of 8 clinical trials recruiting 438 subjects were included for meta-analysis. Pooled analysis revealed that botulinum toxin significantly reduced pain (mean difference [MD] -0.95, 95% CI [-1.63, -0.26], p=0.007) but it was not clinically relevant. No significant effect was detected for grip strength (MD-0.62kg, 95% CI [-2.25, 1.02], p=0.46) or in the risk for adverse events (odds ratio [OR] 0.41, 95% CI [0.05, 3.56], p=0.42) between botulinum toxin injection and control interventions. DISCUSSION: The use of botulinum toxin reached greater pain relief than control interventions and normal saline after a period of 12 to 24 weeks. However, changes in pain relief did not reach clinical significance. The studies that had the greatest reduction in pain used higher doses of botulinum toxin (60 U). Additionally, differences in grip strength and adverse events did not reach statistical or clinical importance. A subanalysis indicated that botulinum toxin outperformed corticosteroid injections in terms of improving grip strength. Botulinum toxin only causes local and minimal side effects such as irritation, ecchymosis, and paralysis. LEVEL OF EVIDENCE: I.

Effect of Statins on Superoxide Dismutase Level: A Systematic Review.

BACKGROUND AND OBJECTIVE: The literature suggests that statins may increase superoxide dismutase (SOD) levels by different mechanisms. These effects may contribute to the antioxidant and anti-inflammatory effects of statins, which are thought to be beneficial in preventing cardiovascular events. However, there are also conflicting results concerning the effect of statins on SOD levels. The goal of this systematic review was to evaluate the effect of statin therapy on SOD activity. METHODS: This systematic review was performed based on the PRISMA statement. The terms ("statin" or "HMG-CoA reductase inhibitor" OR "lipid-lowering agents" OR "Atorvastatin" OR "Simvastatin" OR "Pravastatin" OR "Fluvastatin" OR "Lovastatin") AND ("superoxide dismutase" OR "SOD" OR "anti-oxidative" OR "oxidative stress") were searched in database systems Google Scholar, PubMed/MEDLINE, and Scopus from inception to April 2022. RESULTS: A total of 14 controlled clinical trials - 10 randomized and 4 non-randomized - were found to be eligible. Four studies measured SOD levels in plasma, six in serum, two in red blood cells, one in venous blood, and one on both red blood cells and venous blood matrices. Seven clinical trials used atorvastatin, six used simvastatin, and four used rosuvastatin. Six studies reported an increase in SOD activity, seven found no significant changes, and one showed a reduced SOD activity. CONCLUSION: Our systematic review suggests that treatment with statins has a positive effect on SOD activity. However, evidence from further randomized controlled trials is required to confirm the potential antioxidant effect of statin therapy.

Effect of corticosteroids over plantar fascia thickness in plantar fasciitis: a systematic review and meta-analysis.

OBJECTIVES: Corticosteroid injections have been typically used for the management of plantar fasciitis with apparently good clinical outcomes; however, there is no information of the effect of corticosteroids on the thickness of the plantar fascia which is typically altered in this pathology. We aimed determine whether treatment with corticosteroid injections induces plantar fascia thickness changes in plantar fasciitis. METHODS: MEDLINE, Embase, Web of Science, and Scopus databases were searched for randomized controlled trials (RCT) reporting the use of corticosteroid injection to treat plantar fasciitis to July 2022. Studies must have reported plantar fascia thickness measurement. The risk of bias in all studies was assessed with the Cochrane Risk of Bias 2.0 tool. Meta-analysis was conducted using a random-effects model and the generic inverse variance method. RESULTS: Data from 17 RCT (including 1109 subjects) were collected. The follow-up period ranged from one to six months. Most studies measured the thickness of the plantar fascia at the insertion into the calcaneus using ultrasound. Pooled analysis revealed that corticosteroid injections had no significant effect on plantar fascia thickness (weighted mean differences [WMD], 0.06 mm [95% CI: -0.17, 0.29]; p = 0.61) or pain relief (WMD, 0.12 cm [95% CI: -0.36, 0.61]; p = 0.62) above active controls. CONCLUSION: Corticosteroid injections do not perform better than other common interventions in terms of a decrease of plantar fascia thickness and pain relief for plantar fasciitis.

Importance of Magnesium Status in COVID-19.

A large amount of published research points to the interesting concept (hypothesis) that magnesium (Mg) status may have relevance for the outcome of COVID-19 and that Mg could be protective during the COVID disease course. As an essential element, Mg plays basic biochemical, cellular, and physiological roles required for cardiovascular, immunological, respiratory, and neurological functions. Both low serum and dietary Mg have been associated with the severity of COVID-19 outcomes, including mortality; both are also associated with COVID-19 risk factors such as older age, obesity, type 2 diabetes, kidney disease, cardiovascular disease, hypertension, and asthma. In addition, populations with high rates of COVID-19 mortality and hospitalization tend to consume diets high in modern processed foods, which are generally low in Mg. In this review, we review the research to describe and consider the possible impact of Mg and Mg status on COVID-19 showing that (1) serum Mg between 2.19 and 2.26 mg/dL and dietary Mg intakes > 329 mg/day could be protective during the disease course and (2) inhaled Mg may improve oxygenation of hypoxic COVID-19 patients. In spite of such promise, oral Mg for COVID-19 has thus far been studied only in combination with other nutrients. Mg deficiency is involved in the occurrence and aggravation of neuropsychiatric complications of COVID-19, including memory loss, cognition, loss of taste and smell, ataxia, confusion, dizziness, and headache. Potential of zinc and/or Mg as useful for increasing drug therapy effectiveness or reducing adverse effect of anti-COVID-19 drugs is reviewed. Oral Mg trials of patients with COVID-19 are warranted.

Meta-analysis of the impact of bariatric surgery on circulating TMAO levels as a predictor of cardiovascular disease risk.

INTRODUCTION: Trimethylamine N-oxide (TMAO) is a metabolite of the gut microbiota that is considered a cardiovascular risk factor. Because bariatric surgery (BS) produces changes in the composition of the gut microbiota, the production of TMAO can be compromised. Thus, the purpose of this meta-analysis was to determine the effect of BS on circulating TMAO levels. METHODS: A systematic search was carried on in Embase, PubMed, Web of Science, and Scopus databases. The meta-analysis was conducted using Comprehensive Meta-Analysis (CMA) V2 software. The overall effect size was determined by a random-effects meta-analysis and the leave-one-out approach. RESULTS: Random-effects meta-analysis of 5 studies consisting of 142 subjects demonstrated a significant increase in circulating TMAO levels after BS (SMD: 1.190, 95% CI: 0.521, 1.858, p<0.001; I2:89.30%). CONCLUSION: Considering that levels of TMAO are affected after BS due to gut microbial metabolism alteration, there has been a significant elevation in TMAO concentrations observed to occur after BS in obese subjects.

Association of the triglycerides and glucose index and the homeostatic model assessment of insulin resistance with lipoprotein(a), apolipoprotein AI, and apolipoprotein B concentrations in children with normal-weight.

The aim of this study was to compare the association of the triglycerides and glucose (TyG) index and homeostatic model assessment of insulin resistance (HOMA-IR) with lipoprotein(a) (lp[a]), apolipoprotein AI (apoAI), and apoliprotein B (apoB) concentrations in children with normal-weight. Children with normal weight aged 6-10 years and Tanner 1 stage were included in a cross-sectional study. Underweight, overweight, obesity, smoking, alcohol intake, pregnancy, acute or chronic illnesses, and any kind of pharmacological treatment were exclusion criteria. According to the lp(a) levels, children were allocated into the groups with elevated concentrations and normal values. A total of 181 children with normal weight and an average age of 8.4 ± 1.4 years were enrolled in the study. The TyG index showed a positive correlation with lp(a) and apoB in the overall population (r = 0.161 and r = 0.351, respectively) and boys (r = 0.320 and r = 0.401, respectively), but only with apoB in the girls (r = 0.294); while the HOMA-IR had a positive correlation with lp(a) levels in the overall population (r = 0.213) and boys (r = 0.328). The linear regression analysis showed that the TyG index is associated with lp(a) and apoB in the overall population (B = 20.72; 95%CI 2.03-39.41 and B = 27.25; 95%CI 16.51-37.98, respectively) and boys (B = 40.19; 95%CI 14.50-65.7 and B = 29.60; 95%CI 15.03-44.17, respectively), but only with apoB in the girls (B = 24.22; 95%CI 7.90-40.53). The HOMA-IR is associated with lp(a) in the overall population (B = 5.37; 95%CI 1.74-9.00) and boys (B = 9.63; 95%CI 3.65-15.61).   Conclusion: The TyG index is associated with both lp(a) and apoB in children with normal-weight. What is Known: • The triglycerides and glucose index has been positively associated with an increased risk of cardiovascular disease in adults. What is New: • The triglycerides and glucose index is strongly associated with lipoprotein(a) and apolipoprotein B in children with normal-weight. • The triglycerides and glucose index may be a useful tool to identify cardiovascular risk in children with normal-weight.

Association between the expression of TLR4, TLR2, and MyD88 with low-grade chronic inflammation in individuals with metabolically healthy obesity.

BACKGROUND: Among the Toll-like receptors (TLR) that are dependent of myeloid response protein (MyD88), the TLR4 and TLR2 are directly associated with low-grade chronic inflammation; however, they are not been investigated in subjects with metabolically healthy obesity (MHO). Thus, the objective of this study was to determine the association between the expression of TLR4, TLR2, and MyD88 with low-grade chronic inflammation in individuals with MHO. METHODS AND RESULTS: Men and women with obesity aged 20 to 55 years were enrolled in a cross-sectional study. Individuals with MHO were allocated into the groups with and without low-grade chronic inflammation. Pregnancy, smoking, alcohol consumption, intense physical activity or sexual intercourse in the previous 72 h, diabetes, high blood pressure, cancer, thyroid disease, acute or chronic infections, renal impairment, and hepatic diseases, were exclusion criteria. The MHO phenotype was defined by a body mass index (BMI ≥ 30 kg/m2) plus one or none of the following cardiovascular risk factors: hyperglycemia, elevated blood pressure, hypertriglyceridemia, and low high-density lipoprotein cholesterol. A total of 64 individuals with MHO were enrolled and allocated into the groups with (n = 37) and without (n = 27) inflammation. The multiple logistic regression analysis indicated that TLR2 expression is significantly associated with inflammation in individuals with MHO. In the subsequent analysis adjusted by BMI, TLR2 expression remained associated with inflammation in individuals with MHO. CONCLUSION: Our results suggest that overexpression of TLR2, but not TLR4 and MyD88, is associated with low-grade chronic inflammation in subjects with MHO.

The triglycerides and glucose index is highly associated with non-alcoholic fatty liver disease in overweight and obese women.

BACKGROUND: Although some previous studies have indicated that the triglycerides and glucose (TyG) index is associated with an increased risk of non-alcoholic fatty liver disease (NAFLD), there are still few studies in this field. AIMS: The goal of this study was to assess whether the TyG index is associated with the presence of non-alcoholic fatty liver disease NAFLD in overweight and obese women. METHODS: Overweight and obese women aged 20 to 65 years were enrolled in a cross-sectional study and allocated into the groups with and without NAFLD. Alcohol consumption, pregnancy, normal-weight, positive markers of viral or autoimmune hepatitis, acute or chronic liver disease, renal disease, cardiovascular disease, neoplasia, and intake of hepatotoxic drugs were exclusion criteria. The diagnosis of NAFLD was established by liver ultrasound and the TyG index was calculated as the Ln [fasting triglycerides (mg/dL) × fasting glucose (mg/dL)]/2. RESULTS: A total of 420 participants were enrolled and allocated into the groups with (n = 212) and without (n = 208) NAFLD. In the overall population, the frequency of NAFLD was 50.4%. The logistic regression analysis adjusted by body mass index, waist circumference, and total body fat showed that total cholesterol (OR = 1.004; 95% CI: 1.000-1.007), triglycerides (OR = 1.002; 95% CI: 1.000-1.004), AST (OR = 1.19; 95% CI: 1.15-1.23), ALT (OR = 1.20; 95% CI: 1.15-1.25), and TyG index (OR = 3.15; 95% CI: 1.64-6.06) are significantly associated with NAFLD. CONCLUSIONS: The results show that the TyG index is highly associated with the presence of NAFLD in women with overweight and obesity.

Influence of coffee roasting degree on inflammatory and oxidative stress markers in high-fructose and saturated fat-fed rats.

The objective of this study was to evaluate the effect of roasting coffee degree on inflammatory (NF-kß F-6 and TNF-α) and stress oxidative markers (malondialdehyde (MDA), nitric oxide (NO) end product concentrations, catalase (CAT), and superoxide dismutase (SOD) in high-fructose and saturated fat (HFSFD)-fed rats. Roasting was performed using hot air circulation (200 °C) for 45 and 60 min, obtaining dark and very dark coffee, respectively. Male Wistar rats were randomly assigned to receive a) unroasted coffee, b) dark coffee, c) very dark coffee, or distilled water for the control group (n = 8). Coffee brews (7.4 mL/per day equivalent to 75 mL/day in humans) were given by gavage for sixteen weeks. All treated groups significantly decreased NF-kß F-6 (∼30 % for unroasted, ∼50 % for dark, and âˆ¼ 75 % for very dark group) and TNF-α in the liver compared with the control group. Additionally, TNF-α showed a significant reduction in all treatment groups (∼26 % for unroasted and dark groups, and âˆ¼ 39 % for very dark group) in adipose tissue (AT) compared with the negative control. Regarding oxidative stress makers, all coffee brews exerted antioxidant effects in serum, AT, liver, kidney, and heart. Our results revealed that the anti-inflammatory and antioxidant effects of coffee vary according to the roasting degree in HFSFD-fed rats.

Effects of Coffee Supplementation on Homocysteine and Leptin Levels: A Systematic Review and Meta-analysis of Clinical Trials.

BACKGROUND: It has been reported that the consumption of antioxidant foods and beverages may benefit the development of cardiovascular risk factors. However, the impact of coffee consumption on some of these factors, such as homocysteine and leptin is controversial. Some clinical trials have suggested that coffee administration increases plasma total homocysteine levels, while others have found no significant changes in leptin concentrations. OBJECTIVE: This study aimed to assess the effects of coffee supplementation on homocysteine and leptin concentrations in a meta-analysis of clinical trials. METHODS: PubMed, Web of Science, Scopus, ClinicalTrials.gov, and Google Scholar databases were searched from inception to September 29, 2021. A fixed-effects model and the generic inverse variance weighting method were used for meta-analysis. RESULTS: The meta-analysis demonstrated that coffee administration significantly increases homocysteine levels (WMD: 0.55 µmol/L, 95% CI: 0.17, 0.93, p = 0.005, I2 = 0%) but has no significant changes in leptin concentrations (WMD: 1.34 ng/mL, 95% CI: -0.78, 3.45, p = 0.21, I2 = 0%). Additionally, the sensitivity analysis was robust for both homocysteine and leptin levels. CONCLUSION: The results of the present meta-analysis revealed that coffee supplementation raises serum homocysteine concentrations but has no effect on circulating leptin levels.

Hypomagnesemia and 25-hydroxyvitamin D deficiency in patients with long COVID.

Clinical manifestations related to hypomagnesemia and/or deficiency of vitamin D are frequent in patients with an extended course of coronavirus disease-2019 (long COVID). To evaluate hypomagnesemia and hydroxyvitamin D deficiency in patients with long COVID. A total of 125 adults with a diagnosis of long COVID were enrolled in a cross-sectional study. Participants were allocated into a risk (hypomagnesemia and hydroxyvitamin D deficiency) or control (serum magnesium and hydroxyvitamin D within normal ranges) group. Hypomagnesemia and 25-hydroxyvitamin D deficiency were defined based on serum level ≤1.8 mg/dL and <30 ng/mL, respectively. The number of clinical manifestations of long COVID were significantly higher in the risk compared to the control group. Fatigue, memory loss, attention disorders, joint pain, anxiety, sleep disorders, myalgia, and depression, all of which are related to hypomagnesemia and/or 25-hydroxyvitamin D deficiency, were among the 10 most frequent manifestations in the risk group. The adjusted odds ratio for the association between hypomagnesemia and hydroxyvitamin D deficiency during long COVID was 3.1; 95% CI 2.3-12.4, p=0.005. Our results show that patients suffering with long COVID had a deficiency in magnesium and 25-hydroxyvitamin D which correlated with the number of associated clinical manifestations.

Coffee consumption has no effect on circulating markers of liver function but increases adiponectin concentrations: A systematic review and meta-analysis of randomized controlled trials.

Nonalcoholic fatty liver disease has become the most common liver disorder worldwide, reaching a prevalence of 60% and 24% in patients with chronic liver disease and the general population, respectively. Liver function is often assessed using standard liver tests such as alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transferase, and alkaline phosphatase. Randomized controlled trials (RCTs) investigating the potential beneficial effects of coffee consumption on liver function are scarce and their results are inconclusive. Some clinical trials have shown a significant increase in adiponectin concentrations following coffee consumption; however, there are few studies in this field. Hence, the hypothesis of this meta-analysis of RCTs is that coffee consumption decreases blood markers of liver function and increases adiponectin concentrations. A systematic search was conducted in PubMed-MEDLINE, Scopus, Web of Science, ClinicalTrials.gov, and Google Scholar databases. Meta-analysis was performed using a random-effects model followed by sensitivity analysis. Meta-analysis of 14 RCTs, including a total of 897 subjects, showed that coffee consumption has no significant effect on alanine aminotransferase (weighted mean difference [WMD], -0.89 mg/mL; 95% CI, -2.90 to 1.12; P = .39), aspartate aminotransferase (WMD, -0.29 mg/mL; 95% CI, -1.25 to 0.66; P = .55), gamma-glutamyl transferase (WMD, .10 mg/mL; 95% CI, -3.94 to 4.15; P = .96), alkaline phosphatase (WMD, -4.60 mg/mL; 95% CI, -9.26 to 0.07; P = .05), and lactate dehydrogenase (WMD, -0.65 mg/mL; 95% CI, -10.80 to 9.49; P = .90). However, coffee administration significantly increased adiponectin concentrations (WMD, 1.19 mg/mL; 95% CI, 0.08-2.31; P = .04). The results of this meta-analysis of RCTs suggest that coffee consumption may improve liver dysfunction through the elevation of adiponectin levels; however, further clinical trials are needed to corroborate our findings.

Hyperuricemia is Associated with the Presence of Metabolically Obese Normal-Weight and Metabolically Healthy Obese Phenotypes.

BACKGROUND: It is well-recognized that hyperuricemia is a common abnormality among individuals with metabolic syndrome. AIMS: The objective of this study was to determine whether hyperuricemia is associated with the metabolically obese normal-weight (MONW) and metabolically healthy obese (MHO) phenotypes. METHODS: Men and women equal or greater than 18 years of age were enrolled in a cross-sectional study. Normal-weight subjects were allocated into the MONW or healthy normal-weight (HNW) groups; while obese individuals were divided into the MHO and metabolically unhealthy obese (MUO) subgroups. MONW phenotype was defined by body mass index (BMI) <25.0 kg/m2 accompanied by at least one cardiovascular risk factor (hyperglycemia, elevated blood pressure, hypertriglyceridemia, and low high-density lipoprotein cholesterol), and MHO phenotype was considered in obese subjects (BMI ≥30 kg/m2) without metabolic abnormalities. RESULTS: A total of 567 individuals were enrolled; of them, normal-weight subjects were allocated into the MONW (n = 101) and control (n = 72) groups, whereas obese individuals into the MHO (n = 61) and MUO (n = 333) groups. The multiple logistic regression analysis adjusted by age, gender, and body mass index revealed that hyperuricemia is significantly associated with MONW (OR = 5.14; 95% CI: 1.37-19.29) and MHO (OR = 0.34; 95% CI: 0.14-0.82) phenotypes. CONCLUSION: Results of our study showed that hyperuricemia is associated with both MONW and MHO phenotypes.

The Effects of Statin Therapy on Oxidized LDL and Its Antibodies: A Systematic Review and Meta-Analysis.

Background: Elevated serum low-density lipoproteins (LDL), the substrate for the formation of atherogenic oxidized LDLs (oxLDL), are a causal factor for atherosclerotic cardiovascular disease (ASCVD). Statins are well known to decrease LDL particle concentration and reduce ASCVD morbidity and mortality. Objective: To perform a meta-analysis of the effects of statins (i.e., type, dose, and duration of treatment) on serum levels of oxLDL and on immunoglobulin M (IgM) and immunoglobulin G (IgG) antibody levels against oxLDL. Methods: PubMed, Scopus, Embase, and Web of Science were searched up to February 5th, 2021, for randomized controlled trials (RCT) evaluating the effect of statins on oxLDL and anti-oxLDL antibody levels. Meta-analysis was performed using Comprehensive Meta-Analysis (CMA) V2 software. To evaluate the influence of each study on the overall effect size, a sensitivity analysis was performed using the leave-one-out method. Evaluation of the funnel plot, Begg's rank correlation, and Egger's weighted regression tests was used to assess the presence of publication bias in the meta-analysis. Results: A total of 28 RCTs including 4019 subjects were finally included in the meta-analysis. The results indicated a significant decrease in circulating concentrations of oxLDL after treatment with statins (SMD: -2.150, 95% CI: -2.640, -1.697, p < 0.001). Subgroup analysis found no significant effect of the intensity of statin treatment or statin lipophilicity on the reduction of circulating concentrations of oxLDL. An additional meta-analysis of 3 trials showed that statins did not change the serum levels of IgM and IgG antibodies to oxLDL. Conclusion: Statin therapy decreases serum oxLDL concentrations but does not affect circulating levels of anti-oxLDL antibodies.

Reply to Scarpati, G.; Piazza, O. Comment on "Guerrero-Romero et al. Magnesium-to-Calcium Ratio and Mortality from COVID-19. Nutrients 2022, 14, 1686".

We thank Dr. Scarpati and Dr. Piazza for their interest and comments [...].

Inhibitory effect of Mexican oregano (Lippia graveolens Kunth) extracts on digestive enzymes in vitro, and beneficial impact on carbohydrates and lipids absorption in vivo.

ETHNOPHARMACOLOGICAL RELEVANCE: Although Mexican oregano inhibits digestive enzymes in vitro its effect on the absorption of carbohydrates and lipids in vivo has not been addressed. AIM OF THE STUDY: Assess the effect of Mexican oregano (Lippia graveolens Kunth) on carbohydrates and lipids absorption in vivo. The antioxidant activity also was investigated. MATERIALS AND METHODS: Enzymatic inhibitory action of lipase, α-amylase, and α-glucosidase was evaluated in vitro. Oral lipid (OLTT) and starch tolerance tests (OSTT) were conducted with L. graveolens acetone (O-A) and ethanol (O-E) extracts (at 102 mg/kg body weight equivalent to a 1 g human doses) in male Wistar rats. The antioxidant activity was evaluated through inhibition of lipid peroxidation and scavenging radical. RESULTS: Both extracts exhibited higher inhibitory median concentration (IC50) of lipase activity (1.9 µg/µL for O-E and 1.8 µg/µL for O-A) than the positive control (Orlistat) (0.07 µg/µL). The IC50 of α-amylase was higher (41.8 µg/µL for O-E and 25.2 µg/µL for O-A) than the Acarbose (2.5 µg/µL); while α-glucosidase results showed not statistically differences between groups (∼1.7 µg/µL). The OLTT results showed that both extracts significantly reduced serum triglycerides (∼147 mg/dL for O-E and ∼155 mg/dL for O-A) as compared with negative control group (only lipid load). In the OSTT, glucose levels showed a significant decrease (∼31 mg/dL for O-E and ∼17 mg/dL for O-A) than the negative control group (only starch load). About in vitro antioxidant evaluation, not statistically differences between extracts and positive control (Trolox) were observed for scavenged free radicals (∼2.0 µg/µL); whereas O-A inhibited lipid peroxidation similar to the Trolox (∼0.8 µg/µL IC50). The main chemical composition of both extracts was coumaric acid, luteolin, rutinoside, naringenin, and carvacrol. CONCLUSIONS: Both extracts reduce lipid absorption; whereas O-E decreases carbohydrate absorption in vivo. Both extracts inhibit lipid peroxidation and scavenging free radicals in vitro.

Magnesium-to-Calcium Ratio and Mortality from COVID-19.

Obesity, type 2 diabetes, arterial hypertension, decrease in immune response, cytokine storm, endothelial dysfunction, and arrhythmias, which are frequent in COVID-19 patients, are associated with hypomagnesemia. Given that cellular influx and efflux of magnesium and calcium involve the same transporters, we aimed to evaluate the association of serum magnesium-to-calcium ratio with mortality from severe COVID-19. The clinical and laboratory data of 1064 patients, aged 60.3 ± 15.7 years, and hospitalized by COVID-19 from March 2020 to July 2021 were analyzed. The data of 554 (52%) patients discharged per death were compared with the data of 510 (48%) patients discharged per recovery. The ROC curve showed that the best cut-off point of the magnesium-to-calcium ratio for identifying individuals at high risk of mortality from COVID-19 was 0.20. The sensitivity and specificity were 83% and 24%. The adjusted multivariate regression model showed that the odds ratio between the magnesium-to-calcium ratio ≤0.20 and discharge per death from COVID-19 was 6.93 (95%CI 1.6-29.1) in the whole population, 4.93 (95%CI 1.4-19.1, p = 0.003) in men, and 3.93 (95%CI 1.6-9.3) in women. In conclusion, our results show that a magnesium-to-calcium ratio ≤0.20 is strongly associated with mortality in patients with severe COVID-19.

Normal saline injection produces a therapeutic effect in patients with plantar fasciitis: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Injectable therapies have been increasingly investigated to treat plantar fasciitis in randomized controlled trials (RCT) where normal saline injections are frequently used as placebo. The purpose was to quantify the effect of saline injections and compared against available minimal clinically important difference (MCID) criteria specific for plantar fasciitis to assess if changes were clinically meaningful. METHODS: RCT including a placebo group (normal saline) and reporting changes in pain and functional outcomes in plantar fasciitis were identified through a search in MEDLINE, Embase, Web of Science, and Scopus to February 2022. PRISMA guidelines and a registered protocol (PROSPERO: CRD42020214035) were followed to conduct the study. RESULTS: Pooled analysis of 13 RCT (379 subjects) included for analysis revealed a significant improvement on pain (P < .00001) and functional scores (P < .00001) after normal saline injections. These changes exceeded the established MCID criteria. CONCLUSIONS: Normal saline injections in plantar fasciitis showed a therapeutic effect with statistically and clinically meaningful improvement when administered in the setting of an RCT for up to 12 months. The control of potential confounders influencing the effect of saline injections is required for future research.