Minimal Change Disease Is Associated With Endothelial Glycocalyx Degradation and Endothelial Activation

Endothelial glycocalyx; Glomerular endothelial cell; Minimal change diseaseGlicocàlix endotelial; Cèl·lula endotelial glomerular; Malaltia de canvis mínimsGlicocálix endotelial; Célula endotelial glomerular; Enfermedad de cambios mínimosIntroduction Minimal change disease (MCD) is considered a podocyte disorder triggered by unknown circulating factors. Here, we hypothesized that the endothelial cell (EC) is also involved in MCD. Methods We studied 45 children with idiopathic nephrotic syndrome (44 had steroid sensitive nephrotic syndrome [SSNS], and 12 had biopsy-proven MCD), 21 adults with MCD, and 38 healthy controls (30 children, 8 adults). In circulation, we measured products of endothelial glycocalyx (EG) degradation (syndecan-1, heparan sulfate [HS] fragments), HS proteoglycan cleaving enzymes (matrix metalloprotease-2 [MMP-2], heparanase activity), and markers of endothelial activation (von Willebrand factor [vWF], thrombomodulin) by enzyme-linked immunosorbent assay (ELISA) and mass spectrometry. In human kidney tissue, we assessed glomerular EC (GEnC) activation by immunofluorescence of caveolin-1 (n = 11 MCD, n = 5 controls). In vitro, we cultured immortalized human GEnC with sera from control subjects and patients with MCD/SSNS sera in relapse (n = 5 per group) and performed Western blotting of thrombomodulin of cell lysates as surrogate marker of endothelial activation. Results In circulation, median concentrations of all endothelial markers were higher in patients with active disease compared with controls and remained high in some patients during remission. In the MCD glomerulus, caveolin-1 expression was higher, in an endothelial-specific pattern, compared with controls. In cultured human GEnC, sera from children with MCD/SSNS in relapse increased thrombomodulin expression compared with control sera. Conclusion Our data show that alterations involving the systemic and glomerular endothelium are nearly universal in patients with MCD and SSNS, and that GEnC can be directly activated by circulating factors present in the MCD/SSNS sera during relapse

Rapidly fatal West Nile virus meningoencephalitis in an immunocompetent patient: a case report

Abstract Background West Nile virus (WNV) is a Flaviviridae most often transmitted by mosquitos. Clinical manifestations vary from no symptoms to neuroinvasive disease. Mortality is rare, but patients with neuroinvasive disease have a fatality rate of 4-14%. Diagnosis is made on epidemiological, clinical and serological criteria. Treatment is based on symptomatic and support therapy. WNV neuroinvasive disease seems associated to advancing age and diabetes, but poor prognosis risk factors are still not clearly recognized. During 2017-2018 10 patients affected by WNV infection were admitted to our Hospital (Policlinico of Modena): 3 patients had a rapid fatal outcome and 3 needed intensive care transfer. We report the most representative case. Case Report A 81-yr-old man from Emilia-Romagna was admitted to our unit with a 6 days history of fever (>38℃), fatigue, nausea, vomiting, hiccough and mild cognitive impairment treated with amoxicillin. Past medical history: type 2 diabetes mellitus, arterial hypertension, permanent pacemaker for type 3 atrioventricular block. Referred exposure to farm animals. No recent travels abroad. Chest x-ray showed a retrocardiac opacity, so empiric levofloxacin was started for suspected community acquired pneumonia. After two days the patient began lethargic with a Glasgow Come Score < 8. Neuroinvasive WNV disease was confirmed by electroencephalogram and rachicentesis. Before serologic results acyclovir and dexamethasone were initiated without benefit and patient diedon the fifth day after admission. Conclusions Risk factors for poor prognosis related to WNV Infection are still not clearly identified. Our patient underwent unexpected rapid clinical deterioration before invasive treatment could positively affect prognosis. This underlines the importance of clinical alert to WNV infections during transmission season in endemic areas and the necessity of more data on fatal WNV cases to define criteria to promptly recognize high-risk patients. Keywords encephalitis; meningoencephalitis; neuroinvasive disease; West Nile virus; fatal meningoencephalitis

The Role of Uric Acid in Acute and Chronic Coronary Syndromes.

Uric acid (UA) is the final product of the catabolism of endogenous and exogenous purine nucleotides. While its association with articular gout and kidney disease has been known for a long time, new data have demonstrated that UA is also related to cardiovascular (CV) diseases. UA has been identified as a significant determinant of many different outcomes, such as all-cause and CV mortality, and also of CV events (mainly Acute Coronary Syndromes (ACS) and even strokes). Furthermore, UA has been related to the development of Heart Failure, and to a higher mortality in decompensated patients, as well as to the onset of atrial fibrillation. After a brief introduction on the general role of UA in CV disorders, this review will be focused on UA's relationship with CV outcomes, as well as on the specific features of patients with ACS and Chronic Coronary Syndrome. Finally, two issues which remain open will be discussed: the first is about the identification of a CV UA cut-off value, while the second concerns the possibility that the pharmacological reduction of UA is able to lower the incidence of CV events

JLB: a flexible and effective device in critical patients. Review of clinical cases

JLB catheter (Deltamed Inc) is an alternative way to manage difficult venous access; it is placed under US-guidance in large bore veins, with an easy-sterile approach. Internal jugular vein (IJV) is the first choice for cannulation, followed by subclavian or deep upper-arm veins. The catheter is available in different lengths and gauges, it allows high flow rates and can be left in place up to 30 days. From June 2015 to March 2017, JLB has been positioned in 409 patients: in 354 as primary access in IJV, brachial or subclavian vein; in 55 cases JLB became an introducing line for the Seldinger guidewire and further CVC positioning. All clinical cases were reviewed selecting those with greater clinical relevance. We report 8 cases in which JLB resulted determinant for the patient treatment: a 16 years old obese girl born with perinatal distress, a 78 years old obese woman with hemorrhagic shock caused by gastrointestinal bleeding, a 40 years old man with severe hypokalemia, a 30 years old man with severe sepsis, a 40 years old man with Becker’s muscular dystrophy and severe sepsis, a 40 years old man with multiple myeloma who had to carry out cycles of chemotherapy, a 76 years old man with CMV pancolitis and myelofibrosis who needed parenteral nutrition, antiviral therapy and frequent blood and platelets transfusion. Moreover, it has been useful in elderly patients who needed to carry out palliative care for seniority or cancer lasting up to 30 days . In our experience the JLB catheter is safe, easy to place, quick and cost –effective. It is a valid solution either in unstable patients requiring an immediate access in emergency and stable patients with difficult venous access, in which invasive devices can be considered an over-treatment

Hyperuricemia and chronic kidney disease: to treat or not to treat

Hyperuricemia is common in chronic kidney disease (CKD) and may be present in 50% of patients presenting for dialysis. Hyperuricemia can be secondary to impaired glomerular filtration rate (GFR) that occurs in CKD. However, hyperuricemia can also precede the development of kidney disease and predict incident CKD. Experimental studies of hyperuricemic models have found that both soluble and crystalline uric acid can cause significant kidney damage, characterized by ischemia, tubulointerstitial fibrosis, and inflammation. However, most Mendelian randomization studies failed to demonstrate a causal relationship between uric acid and CKD, and clinical trials have had variable results. Here we suggest potential explanations for the negative clinical and genetic findings, including the role of crystalline uric acid, intracellular uric acid, and xanthine oxidase activity in uric acid-mediated kidney injury. We propose future clinical trials as well as an algorithm for treatment of hyperuricemia in patients with CKD

Role of CD93 in Health and Disease

: CD93 (also known as complement protein 1 q subcomponent receptor C1qR1 or C1qRp), is a transmembrane glycoprotein encoded by a gene located on 20p11.21 and composed of 652 amino acids. CD93 can be present in two forms: soluble (sCD93) and membrane-bound (CD93). CD93 is mainly expressed on endothelial cells, where it plays a key role in promoting angiogenesis both in physiology and disease, such as age-related macular degeneration and tumor angiogenesis. In fact, CD93 is highly expressed in tumor-associated vessels and its presence correlates with a poor prognosis, poor immunotherapy response, immune cell infiltration and high tumor, node and metastasis (TNM) stage in many cancer types. CD93 is also expressed in hematopoietic stem cells, cytotrophoblast cells, platelets and many immune cells, i.e., monocytes, neutrophils, B cells and natural killer (NK) cells. Accordingly, CD93 is involved in modulating important inflammatory-associated diseases including systemic sclerosis and neuroinflammation. Finally, CD93 plays a role in cardiovascular disease development and progression. In this article, we reviewed the current literature regarding the role of CD93 in modulating angiogenesis, inflammation and tumor growth in order to understand where this glycoprotein could be a potential therapeutic target and could modify the outcome of the abovementioned pathologies

Hypertensive disorders of pregnancy and long-term cardiovascular health and outcomes

Introduction The maternal vasculature undergoes significant adaptations during pregnancy to meet the increased metabolic demands of the developing fetus. These adaptations include increased cardiac output and blood volume, as well as reduced systemic vascular resistance. In Hypertensive disorders of pregnancy (HDP) there is an impaired cardiovascular adaptation to pregnancy with effects extending beyond pregnancy. In the present study we aimed to characterize long-term cardiovascular status of women who suffered from HDP. Methods Fifty-eight women who attended at least one post-partum visit and a follow-up visit after at least 5 years from delivery were enrolled in the study. Exclusion criteria included multiple pregnancy, fetal genetic or congenital abnormalities, maternal history of organ transplantation, or chronic renal failure (eGFR≤45ml/min/1.73m2). In the follow-up visit participants underwent a complete cardiovascular assessment including echocardiography and multiparametric vascular function assessment. Results and Discussion Two major cardiovascular events, one stroke and one myocardial infarction, occurred both in women with index-pregnancy complicated by preeclampsia (PE). While not statistically significant, women with HDP-non-PE and PE displayed a trend towards an increased risk of developing composite cardiovascular outcome, and women with PE tended to experience it sooner. Nearly half of the women with a history of HDP, whether PE or HDP-non-PE, developed chronic hypertension. Some women also developed hyperuricemia, chronic kidney disease (CKD), and type 2 diabetes at follow- up, most of them had a previous history of PE. Structural and functional cardiac changes were observed in a few cases, especially among women with PE, and vascular dysfunction was more common in women with a history of HDP compared to those with normotensive pregnancies. Results of the present study adds on literature on long-term cardiovascular impact of HDP and further emphasize the importance of a timely follow-up of women who suffered from HDP and particularly PE

Uric Acid and Risk of Cardiovascular Disease: A Question of Start and Finish

Uric acid (UA) is the final product of purine metabolism and its increase in the circulating blood defines the presence of hyperuricemia commonly considered as a concentration of UA in serum above the threshold level of 7 mg/dL in men and >6 mg/dL in wome

Surprises in cardiology: efficacy of gliflozines in heart failure even in the absence of diabetes

It is now well-established that the therapy of type II diabetes mellitus has undergone a radical change in the past 15 years: countless innovative drugs, such as SGLT2I, able to guarantee an optimization of glycaemic control without causing hypoglycaemia, today represent real therapeutic cornerstones not only for the intrinsic ability of these molecules to ensure better glycaemic control but also for the effects they exert on the cardiovascular system. Several pioneering clinical trials, such as EMPA-REG, CANVAS, and DECLARE-TIMI-58, have demonstrated clear benefits of empagliflozin, canagliflozin, and dapagliflozin, respectively, in reducing cardiovascular risk and diabetes-associated macrovascular complications in the diabetic population. The promising results that emerged from these trials represent the spark that triggered a series of studies aimed at evaluating the efficacy of gliflozines in the treatment of patients with heart failure even in the absence of diabetes. Preliminary results confirm the efficacy of SGLT2I in the treatment of this population, representing a real therapeutic revolution

The Gut Microbiota and Vascular Aging: A State-of-the-Art and Systematic Review of the Literature

The gut microbiota is a critical regulator of human physiology, deleterious changes to its composition and function (dysbiosis) have been linked to the development and progression of cardiovascular diseases. Vascular ageing (VA) is a process of progressive stiffening of the arterial tree associated with arterial wall remodeling, which can precede hypertension and organ damage, and is associated with cardiovascular risk. Arterial stiffness has become the preferred marker of VA. In our systematic review, we found an association between gut microbiota composition and arterial stiffness, with two patterns, in most animal and human studies: a direct correlation between arterial stiffness and abundances of bacteria associated with altered gut permeability and inflammation; an inverse relationship between arterial stiffness, microbiota diversity, and abundances of bacteria associated with most fit microbiota composition. Interventional studies were able to show a stable link between microbiota modification and arterial stiffness only in animals. None of the human interventional trials was able to demonstrate this relationship, and very few adjusted the analyses for determinants of arterial stiffness. We observed a lack of large randomized interventional trials in humans that test the role of gut microbiota modifications on arterial stiffness, and take into account BP and hemodynamic alterations