Evaluation of estimated glomerular filtration rate and clinical variables in systemic sclerosis patients

Objectives: The most important renal complication of systemic sclerosis (SSc) is scleroderma renal crisis (SRC). Many patients demonstrate less severe renal complications, most likely associated with reduced renal blood flow and a consequent reduction in glomerular filtration rate (GFR). The mechanism of this slowly progressive form of chronic renal disease is unclear. The aim of this study was to evaluate GFR by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) and the 7-variable Modification of Diet and Renal Disease (MDRD) equations in SSc patients and to correlate estimated GFR (eGFR) with clinical variables of the disease. Methods: 105 unselected and consecutive patients with SSc were enrolled. Serum creatinine was measured in all patients and GFR was estimated by 7-variable MDRD and CKD-EPI equations. Nailfold videocapillaroscopy was performed in all patients. Results: The mean value of eGFR evaluated by both 7-variable MDRD and CKD-EPI was significantly different (p < 0.0001) in the three capillaroscopic groups and correlated negatively with the severity of capillaroscopic damage (early: 95 ± 16 mL/min and 101 ± 12 mL/min, active: 86 ± 25 mL/min and 95 ± 17 mL/min, late: 76 ± 21 mL/min and 82 ± 21 mL/min). The mean value of eGFR evaluated by 7-variable MDRD (97 ± 23 mL/min vs. 74 ± 15 mL/min, p < 0.0001) and CKD-EPI (0.83 ± 0.20 mL/min vs. 0.68 ± 0.10 mL/min, p < 0.0001) was significantly higher in SSc patients without history of digital ulcers than in those with. Conclusion: We can conclude that in SSc patients without renal involvement, eGFR decreases with the progression of digital vascular damag

In systemic sclerosis skin perfusion of hands is reduced and may predict the occurrence of new digital ulcers

Systemic sclerosis (SSc) patients are at high risk for the development of ischemic digital ulcers (DUs). The aim of this study was to assess in SSc patients a correlation between skin perfusion evaluated by LDPI and DUs and to evaluate the prognostic value of skin perfusion to predict the new DUs occurrence. Fifty eight (47 female, 11 male) SSc patients were enrolled. Skin perfusion of hands and region of interest (ROIs) was measured by Laser Doppler perfusion Imager (LDPI). The proximal-distal gradient (PDG) was present when the perfusion mean difference between ROI1 and ROI2 was &gt; 30 pU. The skin perfusion of hands is lower in SSc patients than in healthy controls. The skin perfusion decreased with severity of capillaroscopic damage. Both mean perfusion of hand and PDG are significantly (p &lt; 0.01 and p &lt; 0.0001, respectively) lower in SSc patients with new DUs than in SSc patients without DUs. Only 2 of 11 SSc patients (18.2%) with PDG developed new digital ulcers, conversely 36 of 47 (76.6%) SSc patients without PDG developed new digital ulcers (p &lt; 0.001). The ROC curves demonstrated a good accuracy of new DUs prediction for PDG (0.78, p &lt; 0.0001). Using this cut-off value of 30 pU, RR for new DUs development in SSc patients without PDG is 4,2 (p &lt; 0.001). LDPI indices could be used in association to the capillaroscopic and clinical findings or serological tests in the identification of patients at high risk of developing DU

Lung ultrasound in systemic sclerosis: correlation with high-resolution computed tomography, pulmonary function tests and clinical variables of disease

Interstitial lung disease (ILD) is a hallmark of systemic sclerosis (SSc). Although high-resolution computed tomography (HRCT) is the gold standard to diagnose ILD, recently lung ultrasound (LUS) has emerged in SSc patients as a new promising technique for the ILD evaluation, noninvasive and radiation-free. The aim of this study was to evaluate if there is a correlation between LUS, chest HRCT, pulmonary function tests findings and clinical variables of the disease. Thirty-nine patients (33 women and 6 men; mean age 51 ± 15.2 years) underwent clinical examination, HRCT, pulmonary function tests and LUS for detection of B-lines. A positive correlation exists between the number of B-lines and the HRCT score (r = 0.81, p &lt; 0.0001), conversely a negative correlation exists between the number of B-lines and diffusing capacity of the lung for carbon monoxide (DLCO) (r = −0.63, p &lt; 0.0001). The number of B-lines increases along with the progression of the capillaroscopic damage. A statistically significant difference in the number of B-lines was found between patients with and without digital ulcers [42 (3–84) vs 16 (4–55)]. We found that the number of B-lines increased with the progression of both HRCT score and digital vascular damage. LUS may therefore, be a useful tool to determine the best timing for HRCT execution, thus, preventing for many patients a continuous and useless exposure to ionizing radiatio

Serum uric acid as a marker of microvascular damage in systemic sclerosis patients

Background: Microvascular damage of skin and internal organs is a hallmark of systemic sclerosis (SSc). Serum uric acid (UA) represents a marker of inflammation and endothelial dysfunction. The aims of this study were to evaluate the correlation between serum UA and intrarenal arterial stiffness evaluated by Doppler ultrasound in SSc patients with normal renal function. We also evaluated the correlation between serum UA and other clinical variables of the disease. Methods: Forty-five SSc patients underwent clinical assessment, Doppler ultrasound of intrarenal arteries with evaluation of resistive index (RI), pulsatile index (PI), and systolic/diastolic ratio (S/D), echocardiography with systolic pulmonary artery pressure (PAPs), baseline pulmonary function tests, and nailfold videocapillaroscopy (NVC). In all patients serum UA was measured. Results: The serum UA showed a significant positive correlation with sCr (r = 0.33, p &lt; 0.0001) and PAPs (r = 0.38, p &lt; 0.01) &gt; and negative correlation with CKD-EPI (r = -0.35, p &lt; 0.01). The mean value of serum UA increased with severity of NVC damage. Using this cut-off value of 4.7 mg/dl, the mean value of Doppler indices of intrarenal stiffness is significantly different (p &lt; 0.05) in SSc patients with low normal or high normal serum UA. Conclusions: Serum UA concentration is higher in patients with high microvascular damage than in patients with low microvascular damage. These preliminary data must be confirmed in large prospective studies

Left ventricular mass and intrarenal arterial stiffness as early diagnostic markers in cardiorenal syndrome type 5 due to systemic sclerosis

Background: Cardiorenal syndrome type 5 (CRS-5) includes a group of conditions characterized by a simultaneous involvement of the heart and kidney in the course of a systemic disease. Systemic sclerosis (SSc) is frequently involved in the etiology of acute and chronic CRS-5 among connective tissue diseases. In SSc patients, left ventricular mass (LVM) can be used as a marker of nutritional status and fibrosis, while altered intrarenal hemodynamic parameters are suggestive of early kidney involvement. Methods: Forty-two consecutive patients with a diagnosis of SSc without cardiac and/or renal impairment were enrolled to assess whether cardiac muscle mass can be related to arterial stiffness. Thirty subjects matched for age and sex were also enrolled as healthy controls (HC). All patients performed echocardiography and renal ultrasound. Results: Doppler indices of intrarenal stiffness and echocardiographic indices of LVM were significantly increased in SSc patients compared to HC. A positive correlation exists between LVM/body surface area and pulsatile index (p &lt; 0.05, r = 0.36), resistive index (p &lt; 0.05, r = 0.33) and systolic/diastolic ratio (p &lt; 0.05, r = 0.38). Doppler indices of intrarenal stiffness and LVM indices were significantly higher in SSc patients with digital ulcers than in SSc patients without a digital ulcer history. Conclusions: SSc is characterized by the presence of microvascular and multiorgan injury. An early cardiac and renal impairment is very common. LVM and intrarenal arterial stiffness can be considered as early markers of CRS onset. The clinical use of these markers permits a prompt identification of organ damage. An early diagnosis allows the appropriate setting of pharmacological management, by slowing disease progression

Epstein-Barr virus lytic infection promotes activation of Toll-like receptor 8 innate immune response in systemic sclerosis monocytes

BACKGROUND: Monocytes/macrophages are activated in several autoimmune diseases, including systemic sclerosis (scleroderma; SSc), with increased expression of interferon (IFN)-regulatory genes and inflammatory cytokines, suggesting dysregulation of the innate immune response in autoimmunity. In this study, we investigated whether the lytic form of Epstein-Barr virus (EBV) infection (infectious EBV) is present in scleroderma monocytes and contributes to their activation in SSc. METHODS: Monocytes were isolated from peripheral blood mononuclear cells (PBMCs) depleted of the CD19+ cell fraction, using CD14/CD16 negative-depletion. Circulating monocytes from SSc and healthy donors (HDs) were infected with EBV. Gene expression of innate immune mediators were evaluated in EBV-infected monocytes from SSc and HDs. Involvement of Toll-like receptor (TLR)8 in viral-mediated TLR8 response was investigated by comparing the TLR8 expression induced by infectious EBV to the expression stimulated by CL075/TLR8/agonist-ligand in the presence of TLR8 inhibitor in THP-1 cells. RESULTS: Infectious EBV strongly induced TLR8 expression in infected SSc and HD monocytes in vitro. Markers of activated monocytes, such as IFN-regulated genes and chemokines, were upregulated in SSc- and HD-EBV-infected monocytes. Inhibiting TLR8 expression reduced virally induced TLR8 in THP-1 infected cells, demonstrating that innate immune activation by infectious EBV is partially dependent on TLR8. Viral mRNA and proteins were detected in freshly isolated SSc monocytes. Microarray analysis substantiated the evidence of an increased IFN signature and altered level of TLR8 expression in SSc monocytes carrying infectious EBV compared to HD monocytes. CONCLUSION: This study provides the first evidence of infectious EBV in monocytes from patients with SSc and links EBV to the activation of TLR8 and IFN innate immune response in freshly isolated SSc monocytes. This study provides the first evidence of EBV replication activating the TLR8 molecular pathway in primary monocytes. Immunogenicity of infectious EBV suggests a novel mechanism mediating monocyte inflammation in SSc, by which EBV triggers the innate immune response in infected cells

Pengaruh Penambahan Abu Ampas Tebu Terhadap Karakteristik Tanah Lempung Ekspansif Di Bojonegoro

Cara untuk memperbaiki karakteristik tanah adalah adalah stabilisasi. Zat aditif yang digunakan sebagai stabilisator dalam penelitian ini adalah abu ampas tebu. Sementara itu, tanah lempung ekspansif yang digunakan adalah tanah dari Desa Ngasem, Kabupaten Bojonegoro. Dalam penelitian ini, digunakan penambahan campuran dengan kadar abu ampas tebu sebesar 8%, 10%, 12%, dan 14% dari berat total campuran. Hasil dari penelitian ini menunjukkan bahwa dengan adanya penambahan kadar 14% abu ampas tebu, batas cair menurun sebesar 26,65%, batas plastis menurun sebesar 35,94%, batas susut meningkat sebesar 940,425%, indeks plastisitas menurun sebesar 19,72%, specific gravity menurun sebesar 7,35%, kadar air optimum meningkat sebesar 23,35%, dan berat isi kering tanah menurun sebesar 13,85% dari kondisi tanah asli. Nilai CBR maksimum didapatkan pada penambahan 12% abu ampas tebu yaitu meningkat sebesar 150,68% pada CBR tak terendam dan 95,34% pada CBR terendam. Nilai pengembangan minimum didapatkan pada penambahan 8% abu ampas tebu yaitu menurun sebesar 94,57%. Pada pengujian pengembangan bebas, nilai pengembangan menurun sebesar 15,35%. Dengan 4 hari pemeraman, nilai CBR tak terendam meningkat sebesar 2,38% dari nilai CBR tak terendam tanpa pemeraman, nilai CBR terendam meningkat sebesar 15,25% dari nilai CBR terendam tanpa pemeraman, dan nilai pengembangan menurun sebesar 77,68% dari nilai pengembangan tanpa pemeraman. Dengan 14 hari pemeraman, nilai CBR tak terendam menurun sebesar 11,13% dari nilai CBR tak terendam tanpa pemeraman, nilai CBR terendam menurun sebesar 12,46% dari nilai CBR terendam tanpa pemeraman, dan nilai pengembangan menurun sebesar 100,298% dari nilai pengembangan tanpa pemeraman. Berdasarkan hasil penelitian tersebut, dapat disimpulkan bahwa abu ampas tebu berpengaruh terhadap peningkatan nilai CBR, penurunan nilai pengembangan, serta karakteristik yang lainnya. Kata

Cardiovascular magnetic resonance imaging in hypertrophic cardiomyopathy:the importance of clinical context

In patients with suspected or established hypertrophic cardiomyopathy (HCM), cardiovascular magnetic resonance (CMR) is widely employed for clinical management, given its multimodality approach capable of providing unique information on cardiac morphology, function, and tissue characterization. Guidance regarding all aspects of HCM diagnosis and management is provided by the comprehensive 2014 European Society of Cardiology (ESC) guidelines on HCM. CMR should be performed in centres with recognized expertise in heart muscle diseases, by physicians who are familiar with the whole HCM disease spectrum, differential diagnoses, and pitfalls. Because CMR is usually performed and interpreted by physicians not directly involved in patient care, detailed, bidirectional, and standardized communication becomes essential to obtain best results and avoid misinterpretation. In order to maximize the potential of CMR, it is of paramount importance that reporting physicians are provided with the essential clinical information and that, in turn, referring physicians are given a core set of CMR morphological, functional, and tissue characterization results following the test. This article aims to summarize the current knowledge on the role of CMR in managing HCM and, in addition, to review the importance of the clinical context in which the report is provided, in both adult and paediatric population, highlighting implications for clinical research

The Efficacy of Sodium Channel Blockers to Prevent Phencyclidine-Induced Cognitive Dysfunction in the Rat: Potential for Novel Treatments for Schizophrenia □ S

ABSTRACT Sodium channel inhibition is a well precedented mechanism used to treat epilepsy and other hyperexcitability disorders. The established sodium channel blocker and broad-spectrum anticonvulsant lamotrigine is also effective in the treatment of bipolar disorder and has been evaluated in patients with schizophrenia. Double-blind placebo-controlled clinical trials found that the drug has potential to reduce cognitive symptoms of the disorder. However, because of compound-related side-effects and the need for dose titration, a conclusive evaluation of the drug&apos;s efficacy in patients with schizophrenia has not been possible. In this series of studies in the rat, we compared the efficacy of the two new molecules to prevent a cognitive deficit induced by the N-methyl-D-aspartic acid receptor antagonist phencyclidine (PCP) in the reversal-learning paradigm in the rat. We also explored the effects of the drugs to prevent brain activation and neurochemical effects of PCP. We found that, like lamotrigine, both GSK2 and GSK3 were able to prevent the deficit in reversal learning produced by PCP, thus confirming their potential in the treatment of cognitive symptoms of schizophrenia. However, higher doses than those required for anticonvulsant efficacy of the drugs were needed for activity in the reversal-learning model, suggesting a lower therapeutic window relative to mechanism-dependent central side effects for this indication