Impact of immunosuppression on incidence of post-transplant diabetes mellitus in solid organ transplant recipients: Systematic review and meta-analysis.

BACKGROUND: Solid organ transplantation is a life-saving intervention for end-stage organ disease. Post-transplant diabetes mellitus (PTDM) is a common complication in solid organ transplant recipients, and significantly compromises long-term survival beyond a year. AIM: To perform a systematic review and meta-analysis to estimate incidence of PTDM and compare the effects of the 3 major immunosuppressants on incidence of PTDM. METHODS: Two hundred and six eligible studies identified 75595 patients on Tacrolimus, 51242 on Cyclosporine and 3020 on Sirolimus. Random effects meta-analyses was used to calculate incidence. RESULTS: Network meta-analysis estimated the overall risk of developing PTDM was higher with tacrolimus (OR = 1.4 95%CI: 1.0-2.0) and sirolimus (OR = 1.8; 95%CI: 1.5-2.2) than with Cyclosporine. The overall incidence of PTDM at years 2-3 was 17% for kidney, 19% for liver and 22% for heart. The risk factors for PTDM most frequently identified in the primary studies were age, body mass index, hepatitis C, and African American descent. CONCLUSION: Tacrolimus tends to exhibit higher diabetogenicity in the short-term (2-3 years post-transplant), whereas sirolimus exhibits higher diabetogenicity in the long-term (5-10 years post-transplant). This study will aid clinicians in recognition of risk factors for PTDM and encourage careful evaluation of the risk/benefit of different immunosuppressant regimens in transplant recipients.

Sodium-Glucose Cotransporter 2 Inhibitors, All-Cause Mortality, and Cardiovascular Outcomes in Adults with Type 2 Diabetes: A Bayesian Meta-Analysis and Meta-Regression.

Background This study aimed to assess the effectiveness of sodium-glucose cotransporter 2 inhibitors in reducing the incidence of mortality and cardiovascular outcomes in adults with type 2 diabetes. Methods and Results We conducted a Bayesian meta-analysis of randomized controlled trials comparing sodium-glucose cotransporter 2 inhibitors with placebo. We used meta-regression to examine the association between treatment effects and control group event rates as measures of cardiovascular baseline risk. Fifty-three randomized controlled trials were included in our synthesis. Empagliflozin, canagliflozin, and dapagliflozin reduced the incidence of all-cause mortality (empagliflozin: rate ratio [RR], 0.79; 95% credibility interval [CrI], 0.63-0.97; canagliflozin: RR, 0.86; 95% CrI, 0.69-1.05; dapagliflozin: RR, 0.86; 95% CrI, 0.72-1.01) and cardiovascular mortality (empagliflozin: RR, 0.78; 95% CrI, 0.61-1.00; canagliflozin: RR, 0.83; 95% CrI, 0.63-1.05; dapagliflozin: RR, 0.88; 95% CrI, 0.71-1.08), with a 90.1% to 98.7% probability for the true RR to be <1.00 for both outcomes. There was little evidence for ertugliflozin and sotagliflozin versus placebo for reducing all-cause and cardiovascular mortality. There was no association between treatment effects for all-cause and cardiovascular mortality and the control group event rates. There was evidence for a reduction in the incidence of heart failure for empagliflozin, canagliflozin, dapagliflozin, and ertugliflozin versus placebo (probability RR <1.00 of ≥99.3%) and weaker, albeit positive, evidence for acute myocardial infarction for the first 3 agents (probability RR <1.00 of 89.0%-95.2%). There was little evidence of any agent except canagliflozin for reducing the incidence of stroke. Conclusions Empagliflozin, canagliflozin, and dapagliflozin reduced the incidence of all-cause and cardiovascular mortality versus placebo. Treatment effects of sodium-glucose cotransporter 2 inhibitors versus placebo do not vary by baseline risk.

Systematic review and meta-analysis of post-transplant diabetes mellitus in liver transplant recipients.

Post-transplant diabetes mellitus (PTDM) compromises long-term survival in liver transplant (LT) recipients. The aim of this study was to determine incidence of PTDM after LT and risk factors associated with it. A literature search was conducted, and prospective studies that reported on the incidence of PTDM in LT adult patients on tacrolimus, sirolimus, or cyclosporine were included. We performed random effects meta-analyses for the incidence of PTDM stratified by immunosuppressant and time period. Of 9817 articles identified, 26 studies were included in the qualitative analysis and 21 studies were eligible for the quantitative analysis representing 79 559 LT recipients in 32 separate treatment arms. The proportion of patients who developed PTDM by two-three years was 0.15 (95% CI: 0.10-0.24) for cyclosporine, 0.23 (95% CI: 0.14-0.36) for tacrolimus, and 0.27 (95% CI: 0.23-0.30) for sirolimus. CONCLUSION: Our results showed that sirolimus-based immunosuppression was associated with a higher incidence of PTDM than tacrolimus or cyclosporine at two-three years. However, there were only two studies that compared all three drugs which is a limitation of the study and requires more studies with patients on sirolimus. Recipient factors increasing the risk of PTDM are older age, male sex, and high BMI.

Can video games enhance surgical skills acquisition for medical students? A systematic review.

OBJECTIVE: To systematically assess literature examining the impact of being a gamer or participating in video-game-based training on surgical skills acquisition amongst medical students. BACKGROUND: Video games and surgical procedures share similar skills such as visuospatial abilities and hand-eye coordination; therefore, video games can be a valuable tool for surgical training amongst medical students. However, comprehensive, up-to-date systematic reviews are necessary to confirm. METHODS: A systematic literature search of PubMed, MEDLINE, and EMBASE was performed in April 2020 with no limits set on the date of publication. Observational and randomized controlled studies were included. Quality and bias were assessed using the Newcastle-Ottawa Scale for nonrandomized studies and the Grading of Recommendations Assessment, Development and Evaluation system for randomized studies. RESULTS: A total of 575 participants from 16 studies were included. The most common surgical skills tested were laparoscopy (n = 283, from 8 studies) and robotic surgery (n = 199, from 5 studies). A history of gaming and video-game-based training were associated with improved metrics in robotic surgery and laparoscopy, respectively. Neither was beneficial in arthroscopy or bronchoscopy. Studies using the Wii U and Underground reported significant improvement in overall laparoscopic performance. CONCLUSION: Video games demonstrate potential as adjunctive training in surgical skill education, with a history of gaming and video-game-based training being beneficial in robotic surgery and laparoscopy, respectively. Methodological heterogeneity amongst included studies limit the ability to make conclusive decisions; thus, future studies with long-term follow-up, larger sample sizes, outcomes stratified by video-game characteristics, and up-to-date technology are necessary.

Enteric dysbiosis in liver and kidney transplant recipients: a systematic review.

Several factors mediate intestinal microbiome (IM) alterations in transplant recipients, including immunosuppressive (IS) and antimicrobial drugs. Studies on the structure and function of the IM in the post-transplant scenario and its role in the development of metabolic abnormalities, infection, and cancer are limited. We conducted a systematic review to study the taxonomic changes in liver (LT) and kidney (KT) transplantation, and their potential contribution to post-transplant complications. The review also includes pre-transplant taxa, which may play a critical role in microbial alterations post-transplant. Two reviewers independently screened articles, and assessed risk of bias. The review identified 13 clinical studies, which focused on adult kidney and liver transplant recipients. Patient characteristics and methodologies varied widely between studies. Ten studies reported increased an abundance of opportunistic pathogens (Enterobacteriaceae, Enterococcaceae, Fusobacteriaceae, and Streptococcaceae) followed by butyrate-producing bacteria (Lachnospiraceae and Ruminococcaceae) in nine studies in post-transplant conditions. The current evidence is mostly based on observational data and studies with no proof of causality. Therefore, further studies exploring the bacterial gene functions rather than taxonomic changes alone are in demand to better understand the potential contribution of the IM in post-transplant complications.

How I Do It - MRI-ultrasound fusion prostate biopsy using the Fusion MR and Fusion Bx systems.

There is increasing evidence to support the use of multiparametric magnetic resonance imaging (MRI) in men at risk for clinically significant prostate cancer to help identify lesions and inform biopsy. Randomized, level 1 evidence demonstrates that men who are managed with MRI and MRI-ultrasound fusion targeted biopsy (MRF-TB) have more clinically significant prostate cancer and less clinically insignificant prostate cancer detected and avoid biopsy altogether more often than men who undergo systematic, whole-gland prostate biopsy (SPB). Furthermore, strategies that incorporate MRF-TB have lower rates of upgrading on radical prostatectomy compared to SPB. However, generalizing this data to wider practice is challenging because there is a learning curve for interpreting MRI and performing MRF-TB, and some of the fusion technologies are better than others. We describe our group's early experience with the Fusion MR and Fusion Bx systems (Focal Healthcare, Toronto, ON, Canada). These products are designed with elastic fusion technology that is user-friendly, intuitive and accurate. The Fusion MR contouring system is straightforward and allows for contouring with several MRI sequences simultaneously. The Fusion Bx biopsy system has a semi-robotic arm that accounts for prostate deformation and patient movement and allows for freehand-like access, which is a seamless transition from SPB for clinicians. There were 68 lesions targeted in the first 51 patients. The overall cancer detection rate was 22%/61%/83% for PI-RADS 3/4/5, respectively. The Gleason grade group 2 prostate cancer or higher rate was 6%/47%/75% for PI-RADS 3/4/5, respectively. There were no major complications in this cohort of patients. Limitations of this study include small number of patients and lack of formal follow up to rule out sepsis. Overall, the Fusion MR and Fusion Bx systems are accurate, straightforward and safe to use for MRF-TB. Early experience does not show any significant learning curve.