Low triiodothyronine syndrome and selenium deficiency - undervalued players in advanced heart failure? A single center pilot study.

BACKGROUND: The function of deiodinases - selenoproteins converting thyroid hormones may be disturbed by oxidative stress accompanying heart failure. Selenium (Se) may be used by glutathione peroxidase, leading to a lack of deiodinase and triiodothyronine (T3). The aim of the study was the evaluation of the prevalence and clinical significance of low T3 syndrome in heart failure and the assessment of the association of low fT3 and Se deficiency. METHODS: The study group consisted of 59 consecutive patients hospitalized due to decompensated HFrEF NYHA III or IV. Exclusion criteria were: thyroid dysfunction, severe systemic disease, treatment with amiodarone, steroids or propranolol. Group A included 9 patients with low free T3 (fT3) concentration below 3.1 pmol/L. Group B consisted of the remaining 50 patients with normal fT3 levels. RESULTS: The prevalence of low T3 syndrome was 15.3%. The prevalence of Se deficiency was 74.6%. We demonstrated correlations between fT3 and main clinical variables (i.e. NT-proBNP, LVEF, hsCRP), but we did not find correlation between fT3 and the Se level. Kaplan-Meier survival analysis showed lower survival probability in patients with low fT3 (p < 0.001). CONCLUSIONS: Low T3 syndrome is frequently found in patients with HFrEF and is associated with a poor outcome. We did not identify any significant correlation between Se and fT3 level.

Correction to: Low triiodothyronine syndrome and selenium deficiency - undervalued players in advanced heart failure? A single center pilot study.

After publication of the original article [1], the authors have notified us of a typing error in spelling Dr. Kabat's name. The original publication has been corrected.

Creatine kinase-MB and red cell distribution width as predictors of contrast-induced nephropathy after percutaneous coronary intervention in acute myocardial infarction.

INTRODUCTION: Contrast-induced nephropathy (CIN) is acute kidney injury (AKI), caused by administration of iodinated contrast media. The reported risk factors of CIN are: pre-existing renal dysfunction, admission anemia, diabetic nephropathy, old age, dehydration, high volume and osmolarity of administered contrast media. Patients with acute myocardial infarction (AMI) have threefold higher risk of developing CIN. The aim of the study was to identify risk factors of CIN among patients who underwent percutaneous coronary intervention (PCI) due to AMI. METHODS: This retrospective single-centre study included 257 patients (mean age, 69.19 ± 1.4 years; men 66.15%) undergoing PCI for AMI between January 2012 and January 2013. Demographic data, type and location of MI, co-morbidities and laboratory results were analysed. RESULTS: CIN was found in 50 out of 257 patients (19.5%). Patients who developed CIN were older (p = 0.001), more commonly had chronic kidney disease (p = 0.01) and lower LVEF (p = 0.01). Baseline Red Cell Distribution Width (RDW) was significantly higher in the CIN group (14.85 ± 4.6 vs. 13.62 ± 1.3, p = 0.001). CK-MB levels on admission were significantly higher in the CIN group compared to the non- CIN group (95.6 ± 129.9 vs. 47.03 ± 61.3, p = 0.001). Multivariate model including "classical" CIN risk actors revealed that only baseline CK-MB level (p = 0.001), age >75 years (p = 0.001) and baseline RDW (p = 0.03) were independent predictors for the development of CIN. CONCLUSION: In conclusion, increased CK-MB on admission as a surrogate of time of ischemia, and increased RDW levels on admission as a marker of chronic in ammation are independently associated with higher risk of CIN among patients treated with primary PCI.

Combined intra-arterial and intra-muscular transfer of Wharton's jelly mesenchymal stem/stromal cells in no-option critical limb ischemia - CIRCULATE N-O CLI Pilot Study.

Introduction: Despite progress in pharmacologic and revascularization therapies, no-option critical limb ischemia poses a major clinical and societal problem. Prior cell-based strategies involved mainly autologous (limited) cell sources. Aim: To evaluate the safety and feasibility of a novel ischemic tissue reparation/regeneration strategy using Wharton's jelly mesenchymal stem/stromal cells (WJMSCs) as an "unlimited" cell source in N-O CLI (first-in-man study, FIM). Material and methods: Enrollment criteria included Rutherford-4 to Rutherford-6 in absence of anatomic/technical feasibility for revascularization and adequate inflow via the common femoral artery with patency of at least one below-the-knee artery. 30 × 106 WJMSCs were administered intra-arterially and intra-muscularly (50%/50%) over 3-6-week intervals (3-6 administrations). Safety, feasibility and potential signals of efficacy were assessed at 12 and 48 months. Results: Five patients (age 61-71, 60% male, Rutherford-6 20%, Rutherford-5 60%, Rutherford-4 20%) were enrolled. WJMSCs were administered per protocol in absence of administration technique-related adverse events. Hyperemia, lasting 12-24 h, occurred in 4/5 subjects. Transient edema and pain (reactive to paracetamol) occurred in 3 (60%) patients. Amputation-free survival was 80% after 12 and 48 months. In those who avoided amputation, ischemic ulcerations healed and Rutherford stage improved. 4/5 patients were free of resting pain after 3-6 doses. Conclusions: This FIM study demonstrated the safety and feasibility of WJMSCs use in patients with N-O CLI and suggested treatment efficacy with ≥ 3 doses. Our findings provide a basis for a randomized, double-blind clinical trial to assess the efficacy of WJMSC-based therapeutic strategy in N-O CLI patients.

Cellular therapies in no-option critical limb ischemia: present status and future directions.

Critical limb ischemia - an advanced stage of lower extremity arterial disease with presence of rest pain and/or ischemic ulcers - remains an important cause of major amputations and disability in developed societies. Novel treatment strategies are urgently needed to prevent (or delay) amputations in particular for patients in whom effective revascularization is no longer feasible for anatomic and/or technical reasons (no-option critical limb ischemia - N-O CLI). Cellular therapies have been gaining the growing attention of researchers and clinicians in the last two decades. Several cell types have been used in pre-clinical and clinical studies, and a number of mechanisms have been proposed to contribute to vascular reparation and regeneration in N-O CLI. Although early trials suggested clinical improvement with use of cell-based therapies in N-O CLI, meta-analyses that included randomized controlled trials have not provided definitive conclusions. Fundamental limitations have involved poorly defined cell lines/populations, limited numbers of study participants and limited follow-up periods, and enrolling patients "too sick to benefit" (such as those in Rutherford class 6). Recent advances include standardized "unlimited" sources of therapeutic cells and better understanding of mechanisms that may contribute to vascular reparation and regeneration. Furthermore, based on recent pre-clinical and clinical studies, cell-free preparations (such as microvesicle-based) are being increasingly developed along with advanced therapy medical products consisting of engineered cells and pro-angiogenic factors.

Bridging anticoagulation in patients treated with vitamin K antagonists prior to trochanteric and hip fracture surgeries: The current practice.

BACKGROUND: The strategies of perioperative bridging anticoagulation in orthopedic surgical patients during oral anticoagulation (OAC) therapy with vitamin K antagonists (VKA) vary from center to center. OBJECTIVES: The aim of this single-center study was to assess the risk of bleeding and thromboembolic events (TEs) in bridged patients on VKA who underwent orthopedic surgery due to trochanteric or hip fracture. MATERIAL AND METHODS: The retrospective study included 64 patients (mean age: 80 years) who received VKA for at least 3 months prior to orthopedic procedure. All subjects were bridged with enoxaparin (40 mg once a day). The control group (n = 69) comprised of age-, sexand procedure-matched patients operated on for the same indications, but with neither a history of VKA therapy nor perioperative bridging anticoagulation. RESULTS: Severe postoperative bleeding occurred in 19 (29.7%) patients from the VKA group and in 13 (18.8%) controls (p = 0.16). Within the VKA group, intertrochanteric fractures (52.6%) and femoral neck fractures (47.4%) occurred more often in patients with bleeding than other lower extremity fractures (0%; p = 0.03). Severe adverse events (SAEs) were more common in the VKA group than in the controls (12.5% vs 1.5%; p = 0.01). Patients from the VKA group did not differ from the controls in the incidence of TEs (6.3% vs 8.9%; p = 0.31). No intrahospital mortality was documented. CONCLUSIONS: Prophylactic administration of enoxaparin is a common strategy of bridging anticoagulation in a hospital setting. This approach does not seem to be associated with an increase in thromboembolic risk nor higher risk of bleeding in orthopedic patients who received VKA preoperatively.