Deep Venous Arterialization for Chronic Limb Threatening Ischemia in Atherosclerosis Patients - A Meta-Analysis.

BACKGROUND: Venous arterialization is an upcoming and novel alternative in chronic limb threatening ischemia (CLTI) patients in the absence of standard revascularization options. The aim of this study is to systematically review and analyze outcomes of venous arterialization. METHODS: A systematic literature search was performed in 5 databases using the PRISMA methodology. Inclusion criteria were English language original research papers on CLTI patients treated with venous arterialization. EXCLUSION CRITERIA: absence of CLTI due to atherosclerosis, duplicate study or reporting of patients, meeting abstract only. Quality and risk of bias were evaluated. Meta-analysis was performed using random effects model on articles that have a sample size of equal or greater than 10. RESULTS: Twelve studies included 442 patients that underwent treatment for 445 limbs (374 patients and 377 limbs underwent venous arterialization while remainder underwent traditional bypass and served as control subjects). Average age was 66 [18 studies, range 37 -91 years], 68% were male [271/366, 15 studies] and 67% diabetic [271/406, 16 studies]). Most limbs (88%, 352/398, 16 studies) had tissue loss. Pooled 30-day mortality was 3.7% (95%-confidence interval [CI] 0.8 -6.6%), 30-day morbidity was 15.5% (95%-CI 3.2 -27.8%), 30-day major adverse cardiovascular event was 5.2% (95%-CI 1.7 -8.6%) and 30-day major adverse limb event was 16.7% (95%-CI 1.5 -31.9%). Pooled 1-year limb-salvage rate was 79.0% (95%-CI 68.7 -90.7) and 1-year survival rate was 85.7% (95%-CI 76.2 -96.4). Studies quality varied significantly across studies. CONCLUSION: Venous arterialization has an acceptable a 1-year limb salvage rate of 79%, however, this is based on low levels of evidence. More randomized controlled trials or high-quality cohort studies are needed to further define the effectiveness of this procedure for CLTI.

Methylene Blue Ameliorates Olfactory Dysfunction and Motor Deficits in a Chronic MPTP/Probenecid Mouse Model of Parkinson's Disease.

Mitochondrial dysfunction and oxidative stress are very prominent and early features in Parkinson's disease (PD) and in animal models of PD. Thus, antioxidant therapy for PD has been proposed, but in clinical trials such strategies have met with very limited success. Methylene blue (MB), a small-molecule synthetic heterocyclic organic compound that acts as a renewable electron cycler in the mitochondrial electron transport chain, manifesting robust antioxidant and cell energetics-enhancing properties, has recently been shown to have significant beneficial effects in reducing nigrostriatal dopaminergic loss and motor impairment in acute toxin models of PD. However, no studies have investigated the impact of this promising agent in chronic models or for olfactory dysfunction, an early non-motor feature of PD. To test the efficacy of low-dose MB for olfactory dysfunction, motor symptoms, and dopaminergic neurodegeneration, mice were injected with ten subcutaneous doses of 25 mg/kg MPTP, plus 250 mg/kg intraperitoneal probenecid or saline/probenecid at 3.5-day intervals. Following the onset of olfactory dysfunction, MPTP/probenecid (MPTP/p) and saline/probenecid mice were provided drinking water with or without 1 mg/kg/day MB. Oral delivery of low-dose MB significantly ameliorated MPTP/p-induced deficits in motor coordination, as well as degeneration of tyrosine hydroxylase (TH)-positive neurons of the substantia nigra and TH-positive terminals in the striatum. Importantly, olfactory dysfunction was ameliorated by MB treatment, whereas this benefit is not observed with currently available anti-Parkinsonian medications. These results indicate that low-dose MB is a promising neuroprotective intervention for both motor and non-motor features of PD.