Cell Therapy for Critical Limb Ischemia: Advantages, Limitations, and New Perspectives for Treatment of Patients with Critical Diabetic Vasculopathy

Abstract Purpose of Review To provide a highlight of the current state of cell therapy for the treatment of critical limb ischemia in patients with diabetes. Recent Findings The global incidence of diabetes is constantly growing with consequent challenges for healthcare systems worldwide. In the UK only, NHS costs attributed to diabetic complications, such as peripheral vascular disease, amputation, blindness, renal failure, and stroke, average £10 billion each year, with cost pressure being estimated to get worse. Although giant leaps forward have been registered in the scope of early diagnosis and optimal glycaemic control, an effective treatment for critical limb ischemia is still lacking. The present review aims to provide an update of the ongoing work in the field of regenerative medicine. Recent advancements but also limitations imposed by diabetes on the potential of the approach are addressed. In particular, the review focuses on the perturbation of non-coding RNA networks in progenitor cells and the possibility of using emerging knowledge on molecular mechanisms to design refined protocols for personalized therapy. Summary The field of cell therapy showed rapid progress but has limitations. Significant advances are foreseen in the upcoming years thanks to a better understanding of molecular bottlenecks associated with the metabolic disorders

Recent advances in KEAP1/Nrf2-targeting strategies by phytochemical antioxidants, nanoparticles, and biocompatible scaffolds for the treatment of diabetic cardiovascular complications

Abstract Significance: Modulation of nuclear factor (erythroid-derived 2)-like 2 (Nrf2)-mediated antioxidant response is a key aspect in the onset of diabetes-related cardiovascular complications. With this review, we provide an overview of the recent advances made in the development of Nrf2-targeting strategies for the treatment of diabetes, with particular attention toward the activation of Nrf2 by natural antioxidant compounds, nanoparticles, and oxidative stress-modulating biocompatible scaffolds. Recent Advances: In the past 30 years, studies addressing the use of antioxidant therapies to treat diabetes have grown exponentially, showing promising but yet inconclusive results. Animal studies and clinical trials on the Nrf2 pathway have shown promising results, suggesting that its activation can delay or reverse some of the cardiovascular impairments in diabetes. Critical Issues: Hyperglycemia- and oscillating glucose levels-induced reactive oxygen species (ROS) accumulation is progressively emerging as a central factor in the onset and progression of diabetes-related cardiovascular complications, including endothelial dysfunction, retinopathy, heart failure, stroke, critical limb ischemia, ulcers, and delayed wound healing. In this context, accumulating evidence suggests a central role for Nrf2-mediated antioxidant response, one of the most studied cellular defensive mechanisms against ROS accumulation. Future Directions: Innovative approaches such as tissue engineering and nanotechnology are converging toward targeting oxidative stress in diabetes. Antioxid. Redox Signal. 36, 707–72

Running Experiments with Confidence and Sanity

Analyzing data from large experimental suites is a daily task for anyone doing experimental algorithmics. In this paper we report on several approaches we tried for this seemingly mundane task in a similarity search setting, reflecting on the challenges it poses. We conclude by proposing a workflow, which can be implemented using several tools, that allows to analyze experimental data with confidence. The extended version of this paper and the support code are provided at https://github.com/Cecca/running-experiments

Feasibility and long-term results of focused radioguided parathyroidectomy using a "low" 37 MBq (1 mCi) (99m)Tc-sestamibi protocol

Aim of the present study was to investigate the feasibility and long-term results of focused radioguided parathyroidectomy using a "low" 37 MBq (1 mCi) (99m)Tc-sestamibi dose protocol compared to conventional "high 740 MBq (20 mCi) (99m)Tc-sestamibi dose protocol" in patients with primary hyperparathyroidism (PHPT). The data of focused radioguided surgery obtained in a group of 320 consecutive PHPT patients with high probability of the presence of a solitary parathyroid adenoma (PA) were studied. All patients underwent preoperative imaging work-up of double-tracer (99m)Tc-pertechnetate/(99m)Tc-sestamibi subtraction parathyroid scintigraphy (Sestamibi scintigraphy) and high resolution neck ultrasound (US). In 301/320 patients (96.6%) focused minimally invasive radioguided surgery was successfully performed by administering a "low" 37 MBq (1 mCi) (99m)Tc-sestamibi dose in the operating room 10 minutes before operation. No major intraoperative complications were recorded. Focused radioguided surgery required a mean time of 32 min and a mean hospital stay of 1.2 days. Local anesthesia was applied in 75 patients, 66 of whom (88%) were patients older than 65 years with comorbidities contraindicating general anesthesia. No case of persistent or recurrent PHPT was observed during post-surgical follow-up (range = 18–70 months; mean +/- SD = 15.3 +/- 9.1 months). Radiation exposure dose to the operating surgeon was 1.2 μSi/hour with the "low 37 MBq (1 mCi) (99m)Tc-sestamibi dose", and less than 1.0 μSi/hour for the other operating-room personnel. Focused low dose radioguided parathyroidectomy is a safe and effective means to localize parathyroid adenomas in patients affected by solitary PA thus reducing by 20 fold the radiation exposure dose to the patients and operating room personnel

Impact of COVID-19 on cardiovascular testing in the United States versus the rest of the world

Objectives: This study sought to quantify and compare the decline in volumes of cardiovascular procedures between the United States and non-US institutions during the early phase of the coronavirus disease-2019 (COVID-19) pandemic. Background: The COVID-19 pandemic has disrupted the care of many non-COVID-19 illnesses. Reductions in diagnostic cardiovascular testing around the world have led to concerns over the implications of reduced testing for cardiovascular disease (CVD) morbidity and mortality. Methods: Data were submitted to the INCAPS-COVID (International Atomic Energy Agency Non-Invasive Cardiology Protocols Study of COVID-19), a multinational registry comprising 909 institutions in 108 countries (including 155 facilities in 40 U.S. states), assessing the impact of the COVID-19 pandemic on volumes of diagnostic cardiovascular procedures. Data were obtained for April 2020 and compared with volumes of baseline procedures from March 2019. We compared laboratory characteristics, practices, and procedure volumes between U.S. and non-U.S. facilities and between U.S. geographic regions and identified factors associated with volume reduction in the United States. Results: Reductions in the volumes of procedures in the United States were similar to those in non-U.S. facilities (68% vs. 63%, respectively; p = 0.237), although U.S. facilities reported greater reductions in invasive coronary angiography (69% vs. 53%, respectively; p < 0.001). Significantly more U.S. facilities reported increased use of telehealth and patient screening measures than non-U.S. facilities, such as temperature checks, symptom screenings, and COVID-19 testing. Reductions in volumes of procedures differed between U.S. regions, with larger declines observed in the Northeast (76%) and Midwest (74%) than in the South (62%) and West (44%). Prevalence of COVID-19, staff redeployments, outpatient centers, and urban centers were associated with greater reductions in volume in U.S. facilities in a multivariable analysis. Conclusions: We observed marked reductions in U.S. cardiovascular testing in the early phase of the pandemic and significant variability between U.S. regions. The association between reductions of volumes and COVID-19 prevalence in the United States highlighted the need for proactive efforts to maintain access to cardiovascular testing in areas most affected by outbreaks of COVID-19 infection

Mycobacterium genavense and avian polyomavirus co-infection in a European Goldfinch (Carduelis carduelis)

Systemic mycobacteriosis associated with avian polyomavirus infection was diagnosed histologically in an 8-year-old, captive European goldfinch with a history of nervous signs. Severe mycobacterial lesions were observed in the central nervous system, lungs, cervical air sacs and adrenal glands, without involvement of the gastrointestinal tract. In addition to mycobacteriosis, intranuclear inclusions, typical of polyomavirus, were identified in the adrenal glands. Polymerase chain reaction assays were used to identify Mycobacterium genavense and finch polyomavirus as the causative agents. The absence of involvement of the gastrointestinal tract and the severity of the lesions in the respiratory tract suggested that inhalation may have been the primary route of infection with M. genavense