Cardiovascular and renal outcomes with SGLT-2 inhibitors versus GLP-1 receptor agonists in patients with type 2 diabetes mellitus and chronic kidney disease: a systematic review and network meta-analysis.

BACKGROUND: Emerging evidence suggests that sodium-glucose cotransporter-2 (SGLT-2) inhibitors and glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are associated with decreased risk of cardiovascular and renal events in type 2 diabetes mellitus (DM) patients. However, no study to date has compared the effect of SGLT-2 inhibitors with that of GLP-1 RAs in type 2 DM patients with chronic kidney disease (CKD). We herein investigated the benefits of SGLT-2 inhibitors and GLP-1 RAs in CKD patients. METHODS: We performed a systematic literature search through November 2020. We selected randomized control trials that compared the risk of major adverse cardiovascular events (MACE) and a composite of renal outcomes. We performed a network meta-analysis to compare SGLT-2 inhibitors with GLP-1 RAs indirectly. Risk ratios (RRs) with corresponding 95% confidence intervals (CI) were synthesized. RESULTS: Thirteen studies were selected with a total of 32,949 patients. SGLT-2 inhibitors led to a risk reduction in MACE and renal events (RR [95% CI]; 0.85 [0.75-0.96] and 0.68 [0.59-0.78], respectively). However, GLP-1 RAs did not reduce the risk of cardiovascular or renal adverse events (RR 0.91 [0.80-1.04] and 0.86 [0.72-1.03], respectively). Compared to GLP-1 RAs, SGLT-2 inhibitors did not demonstrate a significant difference in MACE (RR 0.94 [0.78-1.12]), while SGLT-2 inhibitors were associated with a lower risk of renal events compared to GLP-1 RAs (RR 0.79 [0.63-0.99]). A sensitivity analysis revealed that GLP-1 analogues significantly decreased MACE when compared to placebo treatment (RR 0.81 [0.69-0.95]), while exendin-4 analogues did not (RR 1.03 [0.88-1.20]). CONCLUSIONS: In patients with type 2 DM and CKD, SGLT-2 inhibitors were associated with a decreased risk of cardiovascular and renal events, but GLP-1 RAs were not. SGLT-2 inhibitors significantly decreased the risk of renal events compared to GLP-1 RAs. Among GLP-1 RAs, GLP-1 analogues showed a positive impact on cardiovascular and renal outcomes, while exendin-4 analogues did not.

Fn-EDA (Fibronectin Containing Extra Domain A) in the Plasma, but Not Endothelial Cells, Exacerbates Stroke Outcome by Promoting Thrombo-Inflammation.

Background and Purpose- Cellular Fn-EDA (fibronectin containing extra domain A) is expressed in activated endothelial cells and elevated in circulation in patients with cardiovascular diseases. Although global deficiency of Fn-EDA in mice improves stroke outcome, the specific contribution of plasma versus endothelium Fn-EDA in stroke outcome is currently unknown. We investigated the role of plasma versus endothelial Fn-EDA in stroke exacerbation in the comorbid condition of hyperlipidemia. Methods- We generated novel plasma Fn-EDA-/- ( Fn-EDA fl/fl Alb Cre) and endothelial Fn-EDA-/- ( Fn-EDA fl/fl Tie2 Cre) strains on hyperlipidemic apolipoprotein E-deficient ( ApoE-/-) background. By following the Stroke Therapy Academic Industry Roundtable guidelines, we evaluated stroke outcome in male and female mice. Susceptibility to ischemia/reperfusion injury was evaluated in 2 different models of stroke: intraluminal monofilament and embolic model on days 1, 3, and 7. Quantitative assessment of stroke outcome was evaluated by measuring infarct volume (by magnetic resonance imaging), cerebral blood flow (by laser speckle imaging), neurological and sensory-motor outcome, and postischemic thrombo-inflammation (platelet thrombi, fibrin, neutrophil, phospho-NFκB [nuclear factor κB], TNFα [tumor necrosis factor α], and IL1ß [interleukin 1ß]). Results- Stroke outcome was comparable in ApoE-/- Fn-EDA fl/fl Tie2 Cre and control ApoE-/- Fn-EDA fl/fl mice suggesting endothelial Fn-EDA does not contribute to stroke. ApoE-/- Fn-EDA fl/fl Alb Cre mice exhibited significantly smaller infarcts and improved neurological and sensory-motor outcome at days 1, 3, and 7 in monofilament and embolic models of stroke. Improved stroke outcome was concomitant with enhanced survival, and decreased postischemic thrombo-inflammatory response ( P<0.05 versus ApoE-/- Fn-EDA fl/fl). No sex-based differences were observed. Laser speckle imaging revealed significantly improved regional cerebral blood flow at 1 hour in ApoE-/- Fn-EDA fl/fl Alb Cre mice suggesting plasma Fn-EDA promotes postischemic secondary thrombosis. Coinfusion of anti-Fn-EDA antibody with r-tPA (recombinant tissue-type plasminogen activator) in ApoE-/- mice, 1 hour after embolization, improved stroke outcome with enhanced survival, and improved neurological outcome ( P<0.05 versus r-tPA). Conclusions- Genetic evidence suggests that plasma Fn-EDA exacerbates stroke outcome by promoting postischemic thrombo-inflammation. Interventions targeting plasma Fn-EDA may reduce brain damage after reperfusion.

Retro-intraocular Lens Irrigation-aspiration to Prevent Capsular Block Syndrome at the Hands of Novice Surgeons.

Retro-intraocular lens (IOL) irrigation-aspiration is of paramount importance in order to remove the viscoelastic substance from the retro-IOL space and to prevent any early post-operative capsular block syndrome. However, manoeuvring the IOL to reach the retro-IOL space may be difficult at the hands of novice surgeons despite the use of coaxial or bimanual irrigation-aspiration probes. We describe a simpler and safer technique in order to facilitate the removal of this retro-IOL viscoelastic substance using a 26-Gauge bent-cannula mounted on a 2-ml syringe. The fluid is injected forcefully along with sideways movement of cannula in a single-plane to displace the viscoelastic substance.

Association of the severity of meibomian gland dysfunction with dyslipidemia in Indian population.

PURPOSE: To correlate the severity of meibomian gland dysfunction (MGD) with the serum lipoprotein levels. METHODS: The study was conducted as a prospective observational study over a period of 18 months. Ninety patients diagnosed with MGD were enrolled after they gave their informed consent according to the inclusion-exclusion criteria. Meibomian gland status was evaluated by meibum quality, expressibility, and numerical scoring. Lipid profile was done from an overnight fasting blood sample and evaluated for total cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, and triglycerides (TGs). RESULTS: Patients with higher stages of MGD more often had serum TGs >150 mg/dL, total cholesterol >200 mg/dL, an LDL >130 mg/dL, and serum HDL >40 mg/dL, and there exists an association between increasing stage of MGD, and age, female sex, and increasing values of all the lipid profile components. CONCLUSION: A very strong association exists between increasing age and increasing severity of stage of MGD. A positive association exists between female sex and increasing severity of stage of MGD. A positive association exists between increasing severity of MGD and increasing levels of all the components of lipid profiles, namely LDL, HDL, total cholesterol, and triglycerides.

Spontaneous levitation of dropped nucleus on first post-operative day.

A 60-year-old male patient presenting with gradual painless progressive diminution of vision was diagnosed with nuclear sclerosis grade III (LOCS). Intra-operatively, there was a nuclear drop into the vitreous cavity. The patient was left aphakic and was deferred for further vitreoretinal procedure the next day. On first post-op day, the nucleus fragment (of roughly the same size that had dropped into the vitreous) was seen in the anterior chamber. A gentle ultrasonography B-Scan done for posterior segment evaluation was anechoic. Incision was enlarged and viscoexpression of the nucleus fragment was done followed by thorough anterior vitrectomy. Post-operatively, dilated full fundus examination showed clear vitreous cavity without any evidence of retinal tear or detachment. This was later confirmed by an anechoic ultrasonography B-Scan. After 2 weeks, three-piece foldable IOL was placed in the sulcus with posterior optic capture and the patient attained a best-corrected visual acuity of 6/9P.