Auryan Szalat

Use of polytetrafluoroethylene-covered stent for treatment of coronary artery aneurysm

Coronary artery aneurysm is an uncommon occurrence, yet it is described more often today than in the past as coronary angiography is now routinely used for diagnosis and treatment of ischemic heart disease. However, there is no therapeutic consensus regarding this finding. We present a case of giant coronary artery aneurysm and review the literature on the use of polytetrafluoroethylene‐covered stents as a therapeutic option for this condition. Combined antiaggregant therapy is needed after the procedure. Randomized controlled trials of surgery versus covered stents are necessary to define the best treatment for large coronary artery aneurysms.

In-hospital treatment of hyperglycemia: effects of intensified subcutaneous insulin treatment

ABSTRACT Background: Hyperglycemia is common in hospitalized patients; however, glycemic control obtained during hospitalization is often suboptimal. No methods for achievement of proper glycemic control in this population have been validated in the in-hospital setting. Aims: To study the effect of a novel intensive subcutaneous insulin protocol on the quality of in-hospital glycemic control. Methods: Included in this prospective controlled study were all diabetic patients admitted to the internal medicine departments in a tertiary medical center during a 1-year period. The study was divided into pre-intervention (n = 94), intervention (n = 102) and post-intervention (n = 79) periods. During the intervention period all hospitalized diabetic patients with blood glucose > 200 mg/dL were treated with an intensive multi-injection protocol consisting of two or four times daily regular/NPH insulin injections. Results: Mean glucose level throughout hospitalization was 178.7 ± 47 mg/dL in the intervention period versus 198.8 ± 60 mg/dL in the pre-intervention period ( p < 0.05). During the intervention period, the difference between mean admission and discharge day glucose levels was 43 mg/dL in patients treated with four times daily insulin injections, in contrast to no change noted in the other treatment groups. During the post-intervention period the rate of implementation of the intensive protocol by the internal medicine teams declined to 47.5%, in contrast to a 78.4% implementation rate during the intervention period. This decline was associated with deterioration of glycemic control. Conclusions: The use of intensified insulin regimen improved the glycemic control of hospitalized diabetic patients. Successful incorporation of such intensive protocols into daily medical routines requires close involvement and continuous physician guidance by the hospital diabetes team.

Managing dyslipidaemia in type 2 diabetes mellitus

Glucose-control has a modest beneficial effect on cardiovascular outcomes in patients with type 2 diabetes mellitus. Thus, managing other atherogenic risk factors including hypertriglyceridemia, low HDL-cholesterol and moderately elevated LDL-cholesterol levels with increased small dense LDL-cholesterol fraction, is crucial. Insulin resistance is a key pathophysiologic factor in this population. Treatment starts with lifestyle modifications, but current best programmes have not translated into positive cardiovascular outcomes. Lowering LDL-cholesterol with statins is currently the main treatment strategy, but significant residual risk remains. Attempts to elevate HDL-cholesterol and to reduce triglycerides levels, with niacin or fibrates have not improved cardiovascular prognosis, but addition of ezetimibe, or fibrates in specific patients subgroups, have shown modest benefit. Some glucose-lowering medications and bariatric surgery may also improve diabetic dyslipidemia. Results of three major cardiovascular outcome trials evaluating the effect of lowering LDL-cholesterol with PCSK9 inhibitors in large cohorts that include thousands of diabetic patients are pending.

Can SGLT2 Inhibitors Cause Acute Renal Failure? Plausible Role for Altered Glomerular Hemodynamics and Medullary Hypoxia

Sodium–glucose co-transporter-2 inhibitors (SGLT2i) provide outstanding long-term cardiovascular and renal protection in high-risk patients with type 2 diabetes mellitus. Yet, despite encouraging renal safety outcomes reported in the EMPA-REG study, scattered reports suggest that there might be a risk for acute kidney injury (AKI), which may occasionally be fatal or might require renal replacement therapy. Reduced trans-glomerular pressure with a modest decline in kidney function, an inherent characteristic of SGLT2i therapy, conceivably forms the basis for the long-term renal protection, resembling agents that block the renin–angiotensin–aldosterone (RAAS) axis. Yet, a major decline in kidney function occasionally occurs, often associated with an acute illness or with specific co-administered medications. SGLT2i may lead to AKI by (a) effective volume depletion, due to excessive diuresis, particularly in hemodynamically unstable and volume-depleted patients; (b) excessive decline in trans-glomerular pressure, specifically in patients on RAAS blockade; and (c) induction of renal medullary hypoxic injury, related to enhanced distal tubular transport, especially with concomitant use of agents impairing medullary oxygenation, such as non-steroidal anti-inflammatory drugs and radiocontrast agents. The risk of developing renal impairment with SGLT2i and the role of these suggested mechanisms are yet to be defined, as there are conflicting data and inconsistent reporting with the various agents currently in use.

Diagnosis of ABCC8 congenital hyperinsulinism of infancy in a 20 year-old man evaluated for factitious hypoglycemia.

Context Hypoglycemia is a rare event in healthy adults, and the differential diagnosis includes many diseases, some of which are rare and easily missed. Design, Setting, Description A 20-year-old male military paramedic was referred to our emergency department for investigation of recurrent hypoglycemia episodes during the previous months. Factitious hypoglycemia was excluded, and organic hyperinsulinemic hypoglycemia was diagnosed by the findings from a prolonged fast. The findings from endoscopic ultrasonography and triple-phase computed tomography were normal. Before additional diagnostic tests or exploratory surgery were performed, a deeper interrogation of the patient and his family revealed events compatible with episodes of hypoglycemia since childhood. Moreover, a single event of hypoglycemia during childhood was documented in 1 brother, suggesting the possibility of an inborn, inherited metabolic disease. Because the patient was Ashkenazi Jewish, we suspected the presence of 1 of 2 common founder mutations in the ABCC8 gene, which codes for 1 subunit of the β-cell adenosine triphosphate-sensitive potassium channel, known to cause congenital hyperinsulinism of infancy. Direct sequencing revealed homozygosity for the ABCC8 gene mutation 3989-9 G>A. Conclusions The differential diagnosis of hyperinsulinemic hypoglycemia in a young healthy adult should include genetic disorders of glucose homeostasis. In the Ashkenazi population, rapid and inexpensive screening for 2 founder mutations can confirm the diagnosis, avoiding expensive, invasive, and potentially dangerous diagnostic procedures.

Gender-specific care of diabetes

Diabetic men have benefited in the last 30 years from a significant improvement in total and cardiovascular mortality, whereas diabetic women have had no improvement at all. Moreover, recent research focused on the role of sex hormones in glucose homeostasis, and might account for different pathophysiologic mechanisms in the development of diabetes-related complications. Thus, care of diabetic women is a challenge that requires particular attention. The available data regarding gender-specific care of diabetes mellitus are uneven, rich in some domains but very poor in others. The large prospective trials performed in the last 20 years have assumed that the natural history of diabetes mellitus in men and women, as well as the efficiency of glucose-lowering therapies and management of hyperglycemic-related complications, could be attributable without distinction to men and women. We propose in this paper to analyze the published medical literature according to the specific management of diabetes mellitus in women, and to try to distinguish some particular features. We found important distinctions between diabetic men and women regarding the patterns of abnormalities of glucose regulation, epidemiology, development of diabetes-related complications, ischemic heart disease, morbidity and mortality, impact of cardiovascular risk factors, development of the metabolic syndrome, depression and osteoporosis, as well as the impact of lifestyle modifications or primary and secondary preventions on cardiovascular risk factors, and finally medical therapeutics. Moreover, special considerations were given to some particular aspects of the medical life in diabetic women, such as the features of gestational diabetes mellitus and the management of pregnancy in pregestational diabetic women, use of contraception, hormone-replacement therapy and polycystic ovary syndrome.

Increased Hematocrit During Sodium-Glucose Cotransporter-2 Inhibitor Therapy

Treatment with sodium-glucose cotransporter-2 (SGLT-2) leads to increased hematocrit. Other than hemoconcentration, this phenomenon could be attributed to enhanced erythropoiesis, as indicated by a rise in plasma erythropoietin (EPO) and reticulocytosis [1]. SGLT-2 inhibitors lead to improved renal cortical oxygenation, reflecting reduced transport activity in proximal tubules [2]. In their recent article in JOCMR, Sano et al proposed that improved survival of cortical peritubular interstitial cells with improved cortical oxygenation is the cause of increased EPO with SGLT-2 inhibition [3]. While this hypothesis is interesting, it is not evidence-based, and we would like to propose a more likely alternative explanation, in line with the current understanding of EPO regulation [4], namely intensified hypoxia at the renal cortico-medullary junction. EPO is a hypoxia-triggered gene, up-regulated by hypoxia-inducible factors (HIFs). HIFs are heterodimers consisting of α and β sub-units, that upon attachment to hypoxia response elements along nuclear DNA strands induce trans-activation of numerous HIF-dependent genes, including EPO [4]. Under normoxic conditions, cytoplasmic HIF-α subunits undergo proteasomal degradation, permeated by specific HIF-prolyl hydroxylases. These enzymes are inhibited under hypoxic conditions, leading to cytoplasmic accumulation of HIF-α subunits. Consequently, HIF-α subunits undergo nuclear translocation and binding with HIF-β subunits, promoting HIF-mediated gene responses [4]. Renal parenchymal oxygenation declines in the diabetic kidney under experimental settings, reaching 10 mm Hg at the cortico-medullary junction [5]. We have previously reported that such intensified hypoxia in the diabetic rat kidney leads to stabilization of α subunits of HIF-2 isoforms in peritubular interstitial cells within the deep cortex and the outer medulla, leading to nuclear immunostaining of HIF-2 [6] and that these cells are the origin of EPO upon HIF-2 stabilization [7]. Furthermore, HIF-prolyl hydroxylases have recently been shown to trigger EPO and erythropoiesis in phase 2 clinical trials [8]. While cortical oxygenation improves with SGLT-2 inhibition, medullary oxygenation substantially declines, both in diabetic and in intact rats, conceivably due to increased solute delivery to distal tubular segments, with enhanced regional oxygen expenditure for tubular transport [2]. Therefore, intensified hypoxia at the deep cortex and outer medulla induced by SGLT-2 inhibition is likely the cause of enhanced EPO transcription and consequent reticulocytosis. Another observation in line with this narrative is the reversal of post-renal transplantation erythrocytosis with angiotensin II inhibition [9], conceivably reflecting attenuation of renal parenchymal hypoxia by blocking the renin-angiotensinaldosterone axis (RAAS). Taken together, we conclude that increased EPO levels and erythropoiesis following SGLT-2 inhibition likely result from enhanced hypoxia at the renal cortico-medullary junction, rather than through the amelioration of cortical oxygenation, as suggested by Sano et al [3].

Stepwise CaSR, AP2S1, and GNA11 sequencing in patients with suspected familial hypocalciuric hypercalcemia

PurposePatients with familial hyperparathyroidism and low urinary calcium excretion may have familial hypocalciuric hypercalcemia (FHH) with mutations in one of three genes: the calcium-sensing receptor (CaSR) defining FHH-type 1, the adaptor-related protein complex 2 (AP2S1) related to FHH-type 3 or the G-protein subunit alpha11 (GNA11) associated with FHH-type 2. We aimed to evaluate the presence of mutations in these genes and to identify phenotypic specificities and differences in these patients.Subjects and methodsSelected patients were recruited for genetic evaluation. After informed consent was signed, blood for DNA extraction was obtained and genetic sequencing of CaSR was done. In negative cases, we further performed sequencing of AP2S1 and GNA11.ResultsA total of 10 index cases were recruited. CaSR sequencing yielded three missense heterozygous mutations (30%): c.554G > A (p.I32V) previously characterized by our team, c.1394 G > A (p.R465Q) and a novel expected disease-causing mutation c.2479 A > C (p.S827R). We identified 2 additional patients (20%) carrying the deleterious recurrent mutation c.44G > T (p.R15L) in the AP2S1 gene. No GNA11 mutation was found. Clinically, patients with AP2S1 mutations had significant cognitive and behavioral disorders, and higher blood calcium and magnesium levels than patients with FHH1.ConclusionCaSR and AP2S1 sequencing is worthwhile in patients with familial hyperparathyroidism and phenotype suggesting FHH as it can diagnose up to 50% of cases. GNA11 mutations seem much rarer. Learning disabilities in these patients, associated with higher serum calcium and magnesium levels may suggest the presence of AP2S1 rather than CaSR mutation and may guide the first step in the genetic evaluation.

Correlation between coronary artery calcification by non-cardiac CT and Framingham score in young patients

Background Previous studies have established a correlation between coronary artery calcification (CAC) measured by ECG-gated chest computed tomography (CT) and cardiovascular disease. Recent reports which included asymptomatic patients suggest that CAC measured on non-ECG gated CT is similarly associated with cardiovascular risk. This study investigates the correlation between the Framingham Risk Score (FRS) and an incidental finding of CAC on a non-gated chest CT performed for non-cardiac indications in young and seemingly healthy adults. Methods A cross-sectional study that included 162 CT scans performed in young patients aged 18–50 years old for non-cardiac indications in our institution was conducted. CAC score (CACS) was calculated using the Agatston method. FRS was calculated and compared to the CACS using three different approaches. The correlations between the CACS and several specific factors (i.e. age, body mass index, smoking, statins, etc.), were also evaluated. Results Mean age of patients was 36.43 year old and 105 (64.8%) were male. We found a significant positive correlation between the CACS and the FRS in all three approaches (p<0.05). Increased age, smoking and statin use were the only individual factors clearly associated with an increase in CACS (p = 0.002, p = 0.045 and p = 0.009, respectively). Conclusion This is the first report indicating that incidental CACS identified in non-gated MDCT is also associated with cardiovascular risk evaluated by FRS in a young population. Our findings suggest that young asymptomatic individuals with incidental CAC should be seriously evaluated for cardiovascular risk factors despite presumption of belonging to a low cardiovascular risk category.

Peri-procedural management of antiplatelet therapy, a survey

Antiplatelet therapy is essential to the primary and secondary prevention of cardiovascular disease, but carries a risk of bleeding. Periprocedural management of antiplatelet therapy is a non evidence based field, since no randomized controlled trials have been conducted to compare clinical outcomes between patients continuing and discontinuing antiplatelet therapy. Clinical practice guidelines are based on retrospective data and on expert opinion, and recommenda-