Safety evaluation of bi-layered allogenic keratinocyte and fibroblast skin substitute for diabetic foot ulcers-SAFESKIN-DFU: A Phase 1 clinical trial.

AIM: To assess the safety and efficacy of a local skin substitute product in the treatment of chronic diabetic foot ulcers (DFUs). MATERIALS AND METHODS: Five patients were evaluated over 6 months. Skin substitutes were applied twice at 2-week intervals. Patients were monitored for any possible adverse effects and wound improvement. RESULTS: The results indicated the overall safety of the skin substitute, with only few adverse effects unrelated to this product. Significant reduction in wound size was observed in four patients during the initial 12-week treatment phase, with complete closure in two patients at 24 weeks. CONCLUSIONS: The application of a bi-layered allogeneic keratinocyte and fibroblast skin substitute in patients with chronic DFU was safe and associated with favourable wound healing results. Adherence to standard treatment protocols, including optimal offloading, is essential to maximize the likelihood of successful wound healing.

The association between dietary patterns and disease severity in patients with ulcerative colitis.

Ulcerative colitis (UC) is a chronic inflammatory disease involving the colon and rectum. One of the most modifiable environmental factors affecting UC severity is the patient's dietary pattern. Although the role of dietary patterns on UC aetiology has been investigated previously, its relationship with disease severity has not yet been elucidated. This study examined the association between UC patients' dietary patterns and disease severity. This cross-sectional study was conducted in 340 UC patients. Using an FFQ, food patterns were assessed. Twenty-five food categories were categorised based on the similarity of the nutrient composition of the food using the factor analysis method. A simple clinical colitis activity index was used to determine disease severity. Three dietary patterns were identified based on the factor analysis: healthy, unhealthy and Western dietary pattern. After adjusting for potential confounding factors, patients who were in the highest tertile of healthy dietary pattern compared with the lowest tertile were 92 % less likely to have severe UC (OR: 0·08; 95 % CI: 0·03, 0·22). Also, those in the highest tertile of the Western dietary pattern were 3·86 times more likely to have severe UC than those in the lowest tertile (OR: 3·86; 95 % CI: 1·86, 8·00). Even after controlling for confounding variables, unhealthy dietary pattern did not increase the risk of severe UC. Our data indicate the beneficial role of healthy dietary pattern in amelioration of disease severity in UC patients. To confirm this association, more studies are needed, especially prospective cohort studies.

Effect of ketogenic diet on blood pressure: A GRADE-Assessed systematic review and meta-analysis of randomized controlled trials.

AIMS: Cardiovascular diseases (CVDs) are major causes of mortality around the world. High blood pressure (BP) or hypertension is one of the most significant predisposing factors to CVDs. Ketogenic diets (KDs) have been the center of attention for their possible health benefits. The aim of this analysis is to study the impact of KDs on BP through the existing literature. DATA SYNTHESIS: We investigated the impact of KDs on systolic and diastolic blood pressures (SBP and DBP) conducted in the format of randomized controlled trials (RCTs). Four online databases (PubMed/Medline, SCOPUS, Cochrane Library, and Google Scholar) were searched from inception up to November 2022. Subgroup analyses were carried out to find the sources of heterogeneities. Twenty-three RCTs with 1664 participants were identified. KDs did not exert any significant impacts on SBP (WMD: -0.87 mmHg, 95% CI: -2.05, 0.31) nor DBP (WMD: -0.11 mmHg, 95% CI -1.14, 0.93). Subgroup analyses did not reveal any further information. Also, non-linear dose-response analysis could not detect any associations between the percentage of calorie intake from fat in the KD format and BP levels. CONCLUSION: KDs do not seem to be effective in improving BP. Nonetheless, further investigations are recommended to examine the proportion of fat intake needed to induce favorable clinical impacts.

The effects of Garcinia cambogia (hydroxycitric acid) on lipid profile: A systematic review and meta-analysis of randomized controlled trials.

Garcinia cambogia (GC) has antioxidant, anticancer, antihistamine, and antimicrobial properties. To determine the effect of GC on lipid profiles, a systematic review and meta-analysis was carried out. Up to February 9, 2023, six electronic databases (Web of Science, Cochrane Library, Embase, PubMed, Scopus, and Google Scholar) were searched at any time without limitations. Trials examining the impact of GC on serum levels of total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol (HDL-C) in adults were included. The total effect was shown as a weighted mean difference (WMD) and 95% confidence interval (CI) in a random-effects meta-analysis approach. This systematic review and meta-analysis included 14 trials involving 623 subjects. Plasma levels of TC (WMD: -6.76 mg/dL; CI: -12.39 to -0.59, p-value = 0.032), and TG (WMD: -24.21 mg/dL; CI: -37.84 to -10.58, p < 0.001) were significantly reduced after GC use, and plasma HDL-C (WMD: 2.95 mg/dL; CI: 2.01 to 3.89, p < 0.001) levels increased. low-density lipoprotein cholesterol levels (WMD: -1.15 mg/dL; CI: -16.08 to 13.78, p-value = 0.880) were not significantly affected. The effects of lowering TC and TG were more pronounced for periods longer than 8 weeks. Consuming GC has a positive impact on TC, TG, and HDL-C concentrations. The limitations of this study include the short duration of analyzed interventions and significant heterogeneity. Nevertheless, it is imperative to conduct well-structured, and high-quality long-term trials to comprehensively evaluate the clinical effectiveness of GC on lipid profile, and validate these findings.

The effects of astaxanthin supplementation on liver enzyme levels.

According to previous studies, astaxanthin exerts various biological effects due to its anti-inflammatory and antioxidant capabilities; however, its effects on liver enzymes have not yet been well elucidated. Therefore, we conducted a meta-analysis to assess astaxanthin's effects on liver enzymes. A systematic literature search was conducted using scientific databases including PubMed, Scopus, Web of Science, the Cochrane databases, and Google Scholar up to February 2023 to find relevant randomized controlled trials (RCTs) examining the effects of astaxanthin supplementation on alanine transaminase (ALT), aspartate transaminase (AST), gamma-glutamyl transferase (GGT), and alkaline phosphatase (ALP). A random-effects model was used for the estimation of the pooled weighted mean difference (WMD). Overall, we included five trials involving 196 subjects. The duration of the intervention was between 4 and 48 weeks, and the dose was between 6 and 12 mg/day. ALT levels increased in the intervention group compared to the control group following astaxanthin supplementation (WMD: 1.92 U/L, 95% CI: 0.16 to 3.68, P=0.03), whereas supplementation with astaxanthin had a non-significant effect on AST (WMD: 0.72 U/L, 95% CI: -0.85 to 2.29, P=0.36), GGT (WMD: 0.48 U/L, 95% CI: -2.71 to 3.67, P=0.76), and ALP levels (WMD: 2.85 U/L, 95% CI: -7.94 to 13.63, P=0.60) compared to the placebo group. Our data showed that astaxanthin supplementation increases ALT concentrations in adults without affecting the levels of other liver enzymes. Further long-term and well-designed RCTs are necessary to assess and confirm these findings.

The effects of silymarin consumption on inflammation and oxidative stress in adults: a systematic review and meta-analysis.

BACKGROUND: Owing to the rich phytochemical content of Silymarin, it may effectively manage inflammation and oxidative stress. We, therefore, aimed to examine the existing evidence on the effect of Silymarin consumption on inflammation and oxidative stress factors by conducting a systematic review and meta-analysis of randomized controlled trials. METHODS: A systematic literature search up to September 2023 was completed in PubMed/Medline, Scopus, and Web of Science, to identify eligible RCTs. Heterogeneity tests of the selected trials were performed using the I2 statistic. Random effects models were assessed based on the heterogeneity tests, and pooled data were determined as weighted mean differences with a 95% confidence interval. RESULTS: Fifteen RCTs were included in this meta-analysis. Our findings showed that Silymarin consumption significantly decreased CRP (WMD, - 0.50 mg/L; 95% CI, (- 0.95 to - 0.04); p = 0.03), MDA (WMD, - 1.19 nmol/mL; 95% CI, (- 1.99 to - 0.38); p = 0.004), and IL-6 (WMD, - 0.44 pg/ml; 95% CI, (- 0.75 to - 0.12); p = 0.006). Silymarin consumption had no significant effects on IL-10, TAC, and GSH. A significant non-linear relationship was observed between the duration of the intervention and MDA changes. CONCLUSIONS: Silymarin can help reduce inflammation in patients with diabetes and thalassemia by reducing MDA as an oxidative stress marker and CRP and IL-6 as inflammatory markers.

Short-term effect of dressing with Dermaheal ointment in the treatment of diabetic foot ulcer: A double-blinded randomized controlled clinical trial.

Background and Aims: Diabetic foot ulcers, a major cause of amputations in diabetics, could benefit from natural products as adjuncts to standard care, given the costs and adverse effects of typical therapies. This study aims to evaluate the short-term effects of dressing with Dermaheal ointment in the treatment of DFUs through a double-blinded randomized controlled clinical trial. Methods: This double-blinded, placebo-controlled trial included 50 patients with Wagner's ulcer grade I or II, randomly assigned to Dermaheal and placebo groups (received standard treatment and placebo ointment). The ulcer site was dressed daily for four consecutive weeks with either Dermaheal or placebo ointment. Ulcer healing score (using DFU healing checklist), ulcer size with transparent ruler and largest dimension of ulcer, and pain severity using numerical pain rating score (were recorded at five-time points, including baseline, and on weeks 1, 2, 3, and 4). Also, ulcer healing status was investigated at the trial ended in November 2021. Results: Both groups showed significant improvement in ulcer healing over 4 weeks (p time < 0.001), with more remarkable progress in the Dermaheal group (p group = 0.03). At the trial end, complete ulcer healing was also significantly higher in the Dermaheal group compared to the placebo group (56% vs. 12%, p = 0.002). Both groups exhibited a decrease in ulcer size (p time < 0.001). Considering the baseline ulcer size as a covariate, substantial changes in mean ulcer size were noted in the initial (p = 0.01), second (p = 0.001), third (p = 0.002), and fourth (p = 0.002) weeks of the intervention, showing a preference for the Dermaheal group. However, no significant between-group difference was observed in pain severity levels. Conclusion: Dressing with Dermaheal as a topical treatment shows promise in improving healing and reducing the size of diabetic foot ulcers. Further research is needed to confirm these findings' long-term efficacy.

The effects of Garcinia cambogia (hydroxycitric acid) on serum leptin concentrations: A systematic review and meta-analysis of randomized controlled trials.

OBJECTIVE: The observed impacts of Garcinia cambogia (GC) on serum leptin indicate inconsistency. We performed a systematic review and meta-analysis on randomized controlled trials (RCTs) to evaluate the effectiveness of GC on leptin levels. METHODS: A thorough literature search was carried out using different online databases, including Scopus, Web of Science, PubMed, and Google Scholar, until May 25, 2024. Using random effects, weighted mean differences (WMDs) and corresponding 95 % confidence intervals (CIs) were computed. Standard procedures were followed to account for publication bias, study quality, and statistical heterogeneity. RESULTS: In this meta-analysis, a total of eight eligible trials with 330 participants were ultimately included. Quality assessment showed that half of the included trials were considered to have fair quality, while the other half were deemed to have poor quality. Our analysis, with no indication of publication bias, showed a significantly decreased effect of GC on leptin compared with the placebo (WMD: -5.01 ng/ml; 95 % CI: -9.22 to -0.80, p = 0.02). However, significant heterogeneity was detected between studies (I2 =93.5 %, p < 0.001). The Hartung-Knapp adjustment did not affect our results. Subgroup analysis revealed that GC consumption represents the most effects in trials with sample size ≥ 50 (WMD: -3.63 ng/ml; 95 % CI [-5.51, -1.76], p < 0.001), and mean age of participants ≥ 30 years (WMD: -7.43 ng/ml; 95 % CI [-9.31, -5.56], p < 0.001). CONCLUSIONS: The findings of the present study showed that leptin levels might decline following GC administration. REGISTRATION NUMBER: CRD42023486370.

Consumption of dairy products and odds of ulcerative colitis: An Iranian case-control study.

The association between dairy product consumption and the risk of ulcerative colitis (UC) is not well elucidated. This case-control study examined the association between Iranian adults' dairy consumption and UC risk. We used a valid food frequency questionnaire to analyze dietary intakes in 340 patients with pathologically confirmed cases of UC and 782 controls as part of a case-control research. Pasteurized milk, cheese, and yogurt dietary intakes were calculated along with dairy products. Other variables were acquired using questionnaires. Study participants' mean (± SD) age and body mass index were 41.5 ± 14.1 years and 27.4 ± 4.77 kg/m2, respectively. After adjusting for potential variables, individuals who consumed more total dairy products were less likely to get UC than those who consumed less (odds ratio [OR]: 0.44; 95% confidence interval (CI): 0.24, 0.79). We found a significant reverse association between milk intake (OR: 0.13; 95% CI: 0.07-0.24) and yogurt intake (OR: 0.52; 95% CI: 0.29-0.91) and UC, after controlling for potential confounders. Also, no significant association was found between cheese and UC risk (OR: 1.38; 95% CI: 0.84-2.28). Higher consumption of total dairy products may reduce UC risk. To be specific, milk and yogurt are inversely associated with this disorder. However, no link was found between cheese intake and UC. Longitudinal observational studies, especially cohorts, are needed to further assess these associations.

What is the influence of policosanol supplementation on liver enzymes? A systematic review and dose-response meta-analysis of randomized controlled trials.

OBJECTIVE: Policosanol is a mixture of long chain alcohols refined from sugar cane. Significant reductions in liver enzymes have been observed in some studies. However, the impact of policosanol on liver enzymes remained controversial. The current meta-analysis aims to evaluate the effect of policosanol supplementation on the levels of alanine transaminase (ALT) and aspartate transaminase (AST). METHODS: The literature was systematically searched for studies published up to November 2023 in PubMed/Medline, Google Scholar, EMBASE, and Scopus. Randomized controlled trial (RCT) studies were included to evaluate the intervention effect of policosanol compared to placebo on ALT and AST. DerSimonian and Laird models were used to calculate effect sizes. RESULTS: Twenty-three trials including 2535 participants were included in the study. The combination of effect sizes, regarding the random-effects model, demonstrated significant changes in ALT serum levels after intervention (WMD: -1.48 U/L; 95% CI: -2.33 to -0.64; P = 0.001), and AST (WMD: -1.10 U/L; 95% CI: -1.70 to -0.51; P < 0.001). Subgroup analysis of AST and ALT showed that this reduction effect was most often observed at the dose of 20 mg/d. The dose-response analysis represented a non-significant non-linear connection between the dosage and duration of policosanol intervention in ALT and AST serum reduction. CONCLUSION: Policosanol supplementation exerts a beneficial effect on liver enzymes as well as ALT and AST concentrations in adults. However, further long-term and well-designed RCTs with better quality are needed to further assess and confirm these results.

The effects of ursolic acid on cardiometabolic risk factors: a systematic review and meta-analysis.

Aim: Ursolic acid (UA) has an important biological role in the fight against fat accumulation, insulin resistance, obesity and inflammation. Therefore, in the current review and meta-analysis work, we investigate the effects of UA (dosage range is 50.94 to 450 mg/day) on cardiometabolic risk factors. Materials & methods: After searching the studies up to February 2023, six articles were included in the study. Results: The pooled effect size showed that UA supplementation didn't significantly change body weight, body mass index, waist circumference, body fat percentage, lean body mass, systolic blood pressure, diastolic blood pressure, fasting blood glucose, insulin, triglyceride and high-density lipoprotein compared with control groups. Conclusion: UA supplementation had no significant effect on the cardiometabolic risk factors in adults.

Cardiovascular disease (CVD) is a significant reason for morbidity and mortality. Ursolic acid (UA) has been shown to play important biological roles in the fight against fat accumulation, oxidative stress, insulin resistance via insulin-like growth factor 1, cancer, muscle atrophy, obesity and inflammation responsible for CVD. A systematic review and meta-analysis were conducted up to February 2023; six articles were included in the study and eleven cardiometabolic risk factors were identified. The pooled effect size showed that UA supplementation (dosage range is 50.94 to 450 mg/day) didn't significantly change body weight, body mass index, waist circumference, body fat percentage, lean body mass, systolic blood pressure, diastolic blood pressure, fasting blood glucose, insulin, triglyceride, and high-density lipoprotein compared with control groups.

The effect of conjugated linoleic acid supplementation in comparison with omega-6 and omega-9 on lipid profile: a graded, dose-response systematic review and meta-analysis of randomized controlled trials.

Conjugated linoleic acid (CLA) is a geometrical isomer of linoleic acid, which has anti-inflammatory, anti-diabetic, anti-cancer, and anti-obesity properties. However, the studies reported inconstant results about the CLA-related effects on lipid profiles. As a result, meta-analysis and systematic review were performed to survey the CLA supplementation-related effect on lipid profile including high-density lipoprotein (HDL), low-density lipoprotein (LDL), total cholesterol (TC), and triglycerides (TG). To identify the relevant research, a systematic comprehensive search was initiated on the medical databases such as Scopus and PubMed/Medline until December 2022. The overall effect size was estimated by weighted mean difference (WMD) and 95% confidence interval (CI) in a random effect meta-analysis. In the final quantitative analysis, the meta-analysis considered 35 randomized controlled trials (RCTs) with 1,476 participants (707 controls and 769 cases). The pooled results demonstrated that CLA supplementation, compared with olive oil, significantly increased serum TG levels (WMD: 0.05 mmol/L; 95% CI: 0.01 to 0.1; p = 0.04; I2 = 0.0%, p = 0.91). With regard to TC level, CLA supplementation compared with placebo significantly reduced TC concentrations (WMD: -0.08 mmol/L; 95% CI: -0.14 to -0.02; p < 0.001; I2 = 82.4%). Moreover, the non-linear dose-response analysis indicated a decreasing trend of TC serum level from the 15th week of CLA supplementation compared with olive oil (Pnon-linearity = 0.01). The present meta-analysis and systematic review of 35 RCTs showed that the CLA intervention was able to raise the level of TG in comparison to olive oil; however, it can decrease TC level compared with placebo and olive oil.

Epidemiological Insights into Diabetic Foot Amputation and its Correlates: A Provincial Study.

Background: Diabetic foot ulcer and potential subsequent lower extremity amputation are major complications of diabetes mellitus and are also prominent morbidity factors that could affect patients' quality of life. Objectives: This study aimed to assess the prevalence of diabetic foot amputation and explore correlates of amputation cause and type among subjects with diabetes mellitus in Tehran, Iran. Methods: A descriptive cross-sectional study was conducted to assess the demographic, sociological, and clinical characteristics of subjects who had undergone lower extremity amputation due to diabetic foot ulcers, from 2011 to 2020, in two educational medical centers in Tehran, Iran. We examined the medical records of 4676 individuals who were admitted to Shariati and Sina hospitals due to diabetic foot issues. Information related to patient demographics (age, gender, marital status), social factors (education level, insurance), and clinical data (medical history, laboratory results, and characteristics of diabetic foot ulcers) was collected for subjects who had undergone lower extremity amputation due to diabetic foot ulcer. The collected data was reported using average values, standard deviations and proportions and analyzed using statistical tests. Results: During one decade, 882 out of 4676 (18.8%) patients with diabetic foot ulcers underwent lower extremity amputations of various types in Sina and Shariati hospitals in Tehran, Iran. Of these, 692 (14.5%) were included for further analysis in the study and the rest were excluded due to lack of sufficient recorded data. About 75.9% of the study population was male, and the average age including both sexes was 60 years. About 92.7% were married, and on average, subjects had been afflicted with diabetes mellitus for 15.1 years. Statistical analysis using Pearson's chi-square test showed there was a significant association between the treatment regimen for diabetes mellitus and the type of amputation (P = .01), as well as between the duration of the disease and the cause of amputation (P = .01) and its type (P = .04). Conclusion: diabetes mellitus related treatment regimen and duration of disease are significantly associated with amputation cause and type.

Understanding Why and How Diabetic Patients Lose Their Feet: A Study from Tehran, Iran This study explored patients with diabetes in Tehran, Iran, experience foot problems leading to amputation. We looked at the records of 4676 patients over a decade, finding that 18.8% had lower limb amputations. Key factors included treatment methods for diabetes and the duration of the disease, significantly impacting the cause and type of amputation. These insights can guide better care to prevent such serious complications in patients with diabetes.

The effects of purslane consumption on blood pressure, body weight, body mass index, and waist circumference: a systematic review and meta-analysis of randomised controlled.

The effects of purslane consumption on anthropometric measurements and blood pressure have been studied in numerous experiments. However, the research findings conflict with one another. In order to assess the impact of purslane on weight, body mass index (BMI), waist circumference (WC), systolic blood pressure (SBP), and diastolic blood pressure (DBP), this meta-analysis was carried out. Up until February 2023, PubMed, Web of Science, Scopus, Google Scholar, and the reference lists of the identified pertinent randomised controlled trials (RCTs) were all searched. The random-effects model was used to calculate the effect size and then to describe it as a weighted mean difference (WMD) and 95 % confidence interval (CI) (CRD42023427955). The systematic review was able to incorporate seven RCTs. Meta-analysis showed that purslane significantly decreased body weight (WMD): -0⋅73 kg, 95 % confidence interval (CI): -1⋅37, -0⋅09, P=0⋅025), BMI (WMD: -0⋅35 kg/m2, 95 % CI: -0⋅64, -0⋅07, P=0⋅016), and SBP (WMD: -3⋅64 mmHg, 95 % CI: -6⋅42, -0⋅87, P = 0⋅01), and for WC, there was no discernible effect (WMD: -0⋅86 cm; 95 % CI, -1⋅80 to 0⋅07; P = 0⋅06) and DBP (WMD: -0⋅36 mmHg; 95 % CI, -1⋅75 to 1⋅03; P = 0⋅61). Purslane consumption, especially in participants with a BMI of <30, might play a role in decreasing SBP, body weight, BMI, and WC. Purslane consumption significantly reduced body weight, BMI, and SBP; however, WC and DBP did not experience a reduction. More investigation is needed to verify the impact of purslane consumption on anthropometric parameters and blood pressure.