Mesenchymal stem cell-based therapy for type 1 & 2 diabetes mellitus patients: a systematic review and meta-analysis of randomized controlled trials

Abstract Objective To systematically and statistically evaluate evidence from randomized controlled trials (RCTs) investigating the efficacy and safety of somatic stem cells in achieving glycemic control in type 1 and 2 diabetic patients. Methods Bibliographic databases including PubMed, Scopus, Web of Science, and Cochrane Library were searched from the time of their establishment till January 2024. Obtained records were meticulously screened by title, abstract, and full text to include only RCTs seeking mesenchymal stem cells (MSCs) treatment for type 1 diabetes mellitus (T1DM) and 2 diabetes mellitus (T2DM). Included studies underwent quality assessment using the Cochrane risk of bias 2 tool (ROB2). Results Thirteen studies were deemed eligible for meta-analysis, encompassing 507 patients (T1DM = 199, T2DM = 308). To measure treatment efficacy, the present meta-analysis was conducted on outcomes reported after 12 months following treatment. MSCs therapy group was associated with a significantly reduced glycosylated hemoglobin (HbA1c) compared to the control group, MD = -0.72; 95% CI: [-1.11 to -0.33], P = 0.0003, I2 = 56%. Daily insulin requirement was lower in the MSCs group versus placebo, MD = -14.50; 95% CI: [-19.45 to -9.55], P < 0.00001, I2 = 0%. Pooled fasting C-peptide levels were significantly higher in the MSCs group compared to placebo, MD = 0.24; 95% CI: [0.05 to 0.43], P = 0.01, I2 = 93%. Postprandial blood glucose (PPBG) was observed to be significantly lower in the MSCs arm in contrast to placebo, MD = -11.32; 95% CI: [-16.46 to -6.17], P < 0.0001, I2 = 17%. However, pooled analysis of fasting blood glucose (FBG) was not significantly different between both groups, MD = -6.22; 95% CI: [-24.23 to 11.79], P = 0.50, I2 = 81% at the end of the 12-month follow-up. Conclusion Mesenchymal stem cell-derived therapy is an efficacious glycemia-lowering modality agent compared to conventional therapy in T1DM and T2DM patients. Albeit more sizeable and longer RCTs are warranted to further support and standardize their clinical use

SARS-CoV-2 vaccination modelling for safe surgery to save lives: data from an international prospective cohort study

Background: Preoperative SARS-CoV-2 vaccination could support safer elective surgery. Vaccine numbers are limited so this study aimed to inform their prioritization by modelling. Methods: The primary outcome was the number needed to vaccinate (NNV) to prevent one COVID-19-related death in 1 year. NNVs were based on postoperative SARS-CoV-2 rates and mortality in an international cohort study (surgical patients), and community SARS-CoV-2 incidence and case fatality data (general population). NNV estimates were stratified by age (18-49, 50-69, 70 or more years) and type of surgery. Best- and worst-case scenarios were used to describe uncertainty. Results: NNVs were more favourable in surgical patients than the general population. The most favourable NNVs were in patients aged 70 years or more needing cancer surgery (351; best case 196, worst case 816) or non-cancer surgery (733; best case 407, worst case 1664). Both exceeded the NNV in the general population (1840; best case 1196, worst case 3066). NNVs for surgical patients remained favourable at a range of SARS-CoV-2 incidence rates in sensitivity analysis modelling. Globally, prioritizing preoperative vaccination of patients needing elective surgery ahead of the general population could prevent an additional 58 687 (best case 115 007, worst case 20 177) COVID-19-related deaths in 1 year. Conclusion: As global roll out of SARS-CoV-2 vaccination proceeds, patients needing elective surgery should be prioritized ahead of the general population

Characteristics and outcomes of COVID-19 patients admitted to hospital with and without respiratory symptoms

Background: COVID-19 is primarily known as a respiratory illness; however, many patients present to hospital without respiratory symptoms. The association between non-respiratory presentations of COVID-19 and outcomes remains unclear. We investigated risk factors and clinical outcomes in patients with no respiratory symptoms (NRS) and respiratory symptoms (RS) at hospital admission. Methods: This study describes clinical features, physiological parameters, and outcomes of hospitalised COVID-19 patients, stratified by the presence or absence of respiratory symptoms at hospital admission. RS patients had one or more of: cough, shortness of breath, sore throat, runny nose or wheezing; while NRS patients did not. Results: Of 178,640 patients in the study, 86.4&nbsp;% presented with RS, while 13.6&nbsp;% had NRS. NRS patients were older (median age: NRS: 74 vs RS: 65) and less likely to be admitted to the ICU (NRS: 36.7&nbsp;% vs RS: 37.5&nbsp;%). NRS patients had a higher crude in-hospital case-fatality ratio (NRS 41.1&nbsp;% vs. RS 32.0&nbsp;%), but a lower risk of death after adjusting for confounders (HR 0.88 [0.83-0.93]). Conclusion: Approximately one in seven COVID-19 patients presented at hospital admission without respiratory symptoms. These patients were older, had lower ICU admission rates, and had a lower risk of in-hospital mortality after adjusting for confounders