Safety and Efficacy of Myval Implantation in Patients with Severe Bicuspid Aortic Valve Stenosis—A Multicenter Real-World Experience

Bicuspid aortic valve (BAV) is the most common valvular congenital anomaly and is apparent in nearly 50% of candidates for AV replacement. While transcatheter aortic valve implantation (TAVI) is a recommended treatment for patients with symptomatic severe aortic stenosis (AS) at all surgical risk levels, experience with TAVI in severe bicuspid AS is limited. TAVI in BAV is still a challenge due to its association with multiple and complex anatomical considerations. A retrospective study has been conducted to investigate TAVI’s procedural and 30-day outcomes using the Myval transcatheter heart valve (THV) (Meril Life Sciences Pvt. Ltd. Vapi, Gujarat, India) in patients with severe bicuspid AS. Data were collected on 68 patients with severe bicuspid AS who underwent TAVI with the Myval THV. Baseline characteristics, procedural, 30-day echocardiographic and clinical outcomes were collected. The mean age and STS PROM score were 72.6 ± 9.4 and 3.54 ± 2.1. Procedures were performed via the transfemoral route in 98.5%. Major vascular complications (1.5%) and life-threatening bleeding (1.5%) occurred infrequently. No patient had coronary obstruction, second valve implantation or conversion to surgery. On 30-day echocardiography, the mean transvalvular gradient and effective orifice area were 9.8 ± 4.5 mmHg and 1.8 ± 0.4 cm2, respectively. None/trace aortic regurgitation occurred in 76.5%, mild AR in 20.5% and moderate AR in 3%. The permanent pacemaker implantation rate was 8.5% and 30-day all-cause death occurred in 3.0% of cases. TAVI with the Myval THV in selected BAV anatomy is associated with favorable short-term hemodynamic and clinical outcomes.

Genome-wide Analysis Reflects Novel 5-Hydroxymethylcytosines Implicated in Diabetic Nephropathy

Long-term complications of type 2 diabetes (T2D) are the major causes for T2D-related disability and mortality. Notably, diabetic nephropathy (DN) has become the most frequent cause of end-stage renal disease (ESRD) in most countries. Understanding epigenetic contributors to DN can provide novel insights into this complex disorder and lay the foundation for more effective monitoring tools and preventive interventions, critical for achieving the ultimate goal of improving patient care and reducing healthcare burden. We have used a selective chemical labeling technique (5hmC-Seal) to profile genome-wide distributions of 5-hydroxymethylcytosines (5hmC), a gene activation mark, in patient-derived circulating cell-free DNA (cfDNA). Differentially modified 5hmC genes were identified across T2D patients with DN (n = 12), T2D patients with non-DN vascular complications (non-DN) (n = 29), and T2D patients with no complications (controls) (n = 14). Specifically, differential 5hmC markers between DN and controls revealed relevant pathways such as NOD-like receptor signaling pathway and tyrosine metabolism. A ten-gene panel was shown to provide differential 5hmC patterns between controls and DN, as well as between controls and non-DN patients using a machine learning approach. The 5hmC profiles in cfDNA reflected novel DN-associated epigenetic modifications relevant to the disease pathogenesis of DN. Importantly, these findings in cfDNA, a convenient liquid biopsy, have the potential to be exploited as a clinically useful tool for predicting DN in high risk T2D patients. Keywords: diabetes, nephropathy, epigenetics, 5-hydroxymethylcytosine, cfDNA

Endothelial Dysfunction: An Intermediate Clinical Feature between Urolithiasis and Cardiovascular Diseases

An epidemiological relationship between urolithiasis and cardiovascular diseases has extensively been reported. Endothelial dysfunction is an early pathogenic event in cardiovascular diseases and has been associated with oxidative stress and low chronic inflammation in hypertension, coronary heart disease, stroke or the vascular complications of diabetes and obesity. The aim of this study is to summarize the current knowledge about the pathogenic mechanisms of urolithiasis in relation to the development of endothelial dysfunction and cardiovascular morbidities. Methods: A non-systematic review has been performed mixing the terms “urolithiasis”, “kidney stone” or “nephrolithiasis” with “cardiovascular disease”, “myocardial infarction”, “stroke”, or “endothelial dysfunction”. Results: Patients with nephrolithiasis develop a higher incidence of cardiovascular disease with a relative risk estimated between 1.20 and 1.24 and also develop a higher vascular disease risk scores. Analyses of subgroups have rendered inconclusive results regarding gender or age. Endothelial dysfunction has also been strongly associated with urolithiasis in clinical studies, although no systemic serum markers of endothelial dysfunction, inflammation or oxidative stress could be clearly related. Analysis of urine composition of lithiasic patients also detected a higher expression of proteins related to cardiovascular disease. Experimental models of hyperoxaluria have also found elevation of serum endothelial dysfunction markers. Conclusions: Endothelial dysfunction has been strongly associated with urolithiasis and based on the experimental evidence, should be considered as an intermediate and changeable feature between urolithiasis and cardiovascular diseases. Oxidative stress, a key pathogenic factor in the development of endothelial dysfunction has been also pointed out as an important factor of lithogenesis. Special attention must be paid to cardiovascular morbidities associated with urolithiasis in order to take advantage of pleiotropic effects of statins, angiotensin receptor blockers and allopurinol.

Endovascular Rescue for Renal Artery Pseudoaneurysms following Minimally Invasive Robot-Assisted Partial Nephrectomy—A Case Series

Nephron sparing surgery or partial nephrectomy has been employed ever since in cases of renal tumors with an aim to preserve the function of residual kidney. Lately, there has been increasing adoption in robot-assisted techniques for partial nephrectomy. However, renal surgeries of any kind have always been a hazard for postoperative vascular complications owing to high vascularity of the renal tissues, of which renal artery pseudoaneurysm is one of the most fatal complications. We present a case series where highly super-selective embolization rescues the patient and augments the nephron sparing nature of the precise robot-assisted partial nephrectomy.

Anterior Skull Base Meningioma: Surgical approach and complication avoidance

Background: Endoscopic endonasal approach (EEA) and keyhole transcranial approaches are being increasingly used in anterior skull base meningioma (ASBM) surgery. Objective: We compare tumor resection rates and complication profiles of EEA and supraorbital key hole approach (SOKHA) against conventional transcranial approaches (TCA). Methods: Fifty-four patients with ASBM [olfactory groove (OGM), n=19 and planum sphenoidale/tuberculum sellae (PS/TSM), n=35) operated at a single centre over 7 years were retrospectively analyzed. Results: The overall rate of GTR was higher in OGM (15/19, 78.9%) than PS-TSM group (23/35, 65.7%, p=0.37). GTR rate with OGM was 90% and 75% with TCA and EEA. Death (n=1) following medical complication (TCA) and CSF leak requiring re-exploration (n=2, one each in TCA and EEA) accounted for the major complications in OGM. For the PS/TSM group, the GTR rates were 73.3% (n=11/15), 53.8% (n=7/13) and 71.4% (n=5/7) with TCA, EEA and SOKHA respectively. Seven patients (20%) of PS-TSM developed major postoperative complications including 4 deaths (one each in TCA, SOKHA and 2 in EEA group) and 3 visual deteriorations. Direct and indirect vascular complications were common in lesser invasive approaches to PS-TSM especially if the tumor has encased intracranial arteries. Conclusions: No single approach is applicable to all ASBMs. TCA is still the best approach to obtain GTR but has tissue trauma related problems. SOKHA may be a good alternative to TCA in selected PS-TSMs while EEA may be an alternate option in some OGMs. A meticulous patient selection is needed to derive reported results of EEA for PS-TSM.

A Randomized, Phase 3, Trial of Interferon-α versus Hydroxyurea in Polycythemia Vera and Essential Thrombocythemia

The goal of therapy for essential thrombocythemia (ET) and polycythemia vera (PV) patients is to reduce thrombotic events by normalizing blood counts. Hydroxyurea (HU) and interferon-α (IFN-α) are the most frequently used cytoreductive options for ET and PV patients at high-risk for vascular complications. Myeloproliferative Disorders Research Consortium 112 was an investigator-initiated, phase 3 trial comparing HU to pegylated IFN-α (PEG) in treatment naïve, high-risk ET/PV patients. The primary endpoint was complete response (CR) rate at 12 months. A total of 168 patients were treated for a median of 81.0 weeks. CR for HU was 37% and 35% for PEG (p=0.80) at 12 months. At 24/36 months, CR was 20%/17% for HU and 29%/33% for PEG. PEG led to a greater reduction in JAK2V617F at 24 months, but histopathologic responses were more frequent with HU. Thrombotic events and disease progression were infrequent in both arms, while grade 3/4 adverse events were more frequent with PEG (46% vs. 28%). At 12 months of treatment there was no significant difference in CR rates between HU and PEG. This study indicates that PEG and HU are both effective treatments for PV and ET. With longer treatment PEG was more effective in normalizing blood counts and reducing driver mutation burden, while HU produced more histopathologic responses. Despite these differences, both agents did not differ in limiting thrombotic events and disease progression in high-risk ET/PV patients. (Funded by the National Cancer Institute, 5P01CA108671-09; clinicaltrials.gov number (NCT01259856)

Zinc Homeostasis in Diabetes Mellitus and Vascular Complications

Oxidative stress represents an impaired metabolic system that promotes damage to cells and tissues. This is the predominant factor that leads to the development and progression of diabetes and diabetic complications. Research has indicated that zinc plays a consequential mechanistic role in the protection against oxidative stress as zinc is required for the proper functioning of the antioxidant system, the suppression of inflammatory mediators, and the modulation of zinc transporters. Recently, the mechanisms surrounding ZnT8, ZIP7, and metallothionein have shown to be of particular pathogenic importance and are considered as potential therapeutic targets in disease management. The literature has shown that zinc dysregulation is associated with diabetes and may be considered as a leading contributor to the deleterious vascular alterations exhibited by the disease. Although further investigation is required, studies have indicated the favorable use of zinc supplementation in the protection against and prevention of oxidative stress and its consequences over the course of the condition. This review aims to provide a comprehensive account of zinc homeostasis, the oxidative mechanisms governed by zinc status, current therapeutic targets, and the impact of zinc supplementation in the prevention of disease onset and in mitigating vascular complications.

Fetuin-A and risk of diabetes-related vascular complications: a prospective study

Background Fetuin-A is a hepatokine which has the capacity to prevent vascular calcification. Moreover, it is linked to the induction of metabolic dysfunction, insulin resistance and associated with increased risk of diabetes. It has not been clarified whether fetuin-A associates with risk of vascular, specifically microvascular, complications in patients with diabetes. We aimed to investigate whether pre-diagnostic plasma fetuin-A is associated with risk of complications once diabetes develops. Methods Participants with incident type 2 diabetes and free of micro- and macrovascular disease from the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam cohort (n = 587) were followed for microvascular and macrovascular complications (n = 203 and n = 60, respectively, median follow-up: 13 years). Plasma fetuin-A was measured approximately 4 years prior to diabetes diagnosis. Prospective associations between baseline fetuin-A and risk of complications were assessed with Cox regression. Results In multivariable models, fetuin-A was linearly inversely associated with incident total and microvascular complications, hazard ratio (HR, 95% CI) per standard deviation (SD) increase: 0.86 (0.74; 0.99) for total, 0.84 (0.71; 0.98) for microvascular and 0.92 (0.68; 1.24) for macrovascular complications. After additional adjustment for cardiometabolic plasma biomarkers, including triglycerides and high-density lipoprotein, the associations were slightly attenuated: 0.88 (0.75; 1.02) for total, 0.85 (0.72; 1.01) for microvascular and 0.95 (0.67; 1.34) for macrovascular complications. No interaction by sex could be observed (p > 0.10 for all endpoints). Conclusions Our data show that lower plasma fetuin-A levels measured prior to the diagnosis of diabetes may be etiologically implicated in the development of diabetes-associated microvascular disease.

Endovenous Iliocaval Revascularization for Transplant Kidney Salvage

Purpose: We report the case of a venous iliocaval recanalization to preserve a transplant kidney. Case Report: A young patient with a nephrotic syndrome caused by focal segmental glomerulosclerosis (FSGS) underwent a robot-assisted living-donor kidney transplant. The postoperative course was uneventful; serum creatinine at discharge was 1.51 mg/dL (normal range = 0.72–1.17 mg/dL). In the course of the following months, the patient was readmitted repeatedly due to acute kidney failure not related to rejection, recurrent FSGS, or anastomotic stenosis. All episodes started after prolonged standing and renal function improved after bed rest. Several hospital admissions and investigations later, phlebography revealed an occlusion of the inferior vena cava (IVC) and both common iliac veins with large collateral vessels through the azygos system. An endovenous recanalization of the iliocaval tract was performed, with subsequent normalization of transplant kidney function. Conclusion: Vascular complications after renal transplantation are an important cause of graft loss. We present an endovenous treatment option for a chronic occlusion of the IVC and common iliac vein with intermittent venous congestion as a cause of transplant failure.