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Background and objectives: Vascular calcification is an integral part of atherosclerosis and has been reported to be an independent risk factor for cardiovascular diSsease. Intra Cranial Arterial Calcifications (ICAC) in maintenance hemodialysis (MHD) is highly prevalent. Materials and Methods: The aim of this retrospective study was to assess the predictors and outcomes of ICAC in MHD patients compared to a control group without kidney disease. A blinded neuroradiologist graded ICAC in brain imaging (computerized tomography) of MHD patients. Age- and sex-matched patients with normal kidney function served as the control group. Results: A total of 280 patients were included in the cohort; 140 of them were MHD patients with a mean ICAC score of 2.3 ± 0.2 versus a mean ICAC score of 1.4 ± 0.2 in the control group (p < 0.01). More than 90% of hemodialysis patients in our study had some degree of ICAC. Lower albumin and higher phosphorus and CRP levels were associated with increased ICACs. The multivariate analysis model for predictors of 1-year mortality demonstrated an increased odds ratio for mortality as the ICAC score increased. Conclusions: ICAC is very prevalent among MHD patients and results not simply from passive deposition of calcium and phosphate but rather from complex and active processes involving inflammation and structural changes in blood vessels. ICAC independently predicted all-cause mortality and may help with risk stratification of this high-risk population. [ABSTRACT FROM AUTHOR]

Introduction: Patients with end stage kidney disease undergoing maintenance hemodialysis (MHD) are prone to malnutrition and infections. Objective: The objective of this study was to evaluate the effect of polymorphonuclear (PMN) cell dysfunction on clinical outcomes of MHD patients, in association with nutritional status. Methods: This prospective study investigated 39 MHD patients by evaluating the oxidative activity of their PMN cells using Phorbol 12‐Myristate‐13‐Acetate (PMA) stimulation. Blood samples were taken from each participant at dialysis initiation. Demographics, laboratory data, and clinical outcomes during a 24‐month follow‐up period were obtained from electronic medical records. Results: Phagocytic activity was described in percentiles of mean fluorescence intensity (MFI) of PMA levels. There were no differences in comorbidities between patients with low or high MFI‐PMA percentiles. Patients in the lowest (25th) MFI‐PMA percentile (N = 10) had poorer nutritional status and more frequent severe infections compared to the other 29 patients (4.3 ± 3.4 events versus 2 ± 2.2 events, p = 0.017). Furthermore, they had more frequent hospitalizations (>3) due to infections (70% versus 41%, p = 0.073) and their mortality rate was higher (80% versus 31%, p = 0.007). The odds ratio for all‐cause mortality was 8.85. In multivariate analysis, the MFI‐PMA percentile and ischemic heart disease were the strongest predictors of all‐cause mortality (p = 0.02 and p = 0.005, respectively). Conclusions: Low MFI‐PMA levels were associated with poor nutritional status and adverse clinical outcomes and might serve as a prognostic biomarker, predicting severe infections and mortality among malnourished MHD patients. [ABSTRACT FROM AUTHOR]

Background: COVID‐19 vaccinations have a central role in decreasing severe SARS‐CoV‐2 disease complications. This study investigated the long‐term humoral immune response to BNT162b2 vaccine among hemodialysis (HD) versus peritoneal dialysis (PD) patients, and their relative risk for COVID‐19 infection. Methods: This prospective, observational study included maintenance HD and PD patients who had received at least two BNT162b2 vaccine doses. Levels of antibodies targeting SARS‐CoV‐2 spike protein were measured 6 and 12 months after the first vaccine dose, and 2–3 weeks after the third and fourth vaccine doses. Patients were divided according to dialysis modality (HD or PD). Humoral response was evaluated at different time points among different vaccine regimens (two vs. three vs. four doses of vaccine). An adjusted multivariate model was used to assess cumulative risk for SARS‐CoV‐2 infection. Results: Eighty‐seven HD and 36 PD patients were included. Among them, 106 (86%) received at least three vaccine doses. Both HD and PD patients demonstrated marked increases in humoral response 2–3 weeks after the third dose (mean anti‐S antibody increased from 452 ± 501 AU/mL to 19,556 ± 14,949 AU/mL, p < 0.001). By 6 months after the third dose, antibody titers had declined significantly (mean anti‐S antibody 9841 ± 10,493 AU/mL, p < 0.001). HD patients had higher risk for SARS‐CoV‐2 infection than PD patients (OR 4.4 [95% CI 1.4–13.6], p = 0.006). In multivariate analysis, the most important predictor for SARS‐CoV‐2 infection was dialysis modality. Conclusion: This study found a high antibody response rate after the third and fourth doses of BNT162b2 vaccine among dialysis patients. Hemodialysis as dialysis modality is an important predictor of COVID‐19 infection, despite similar humoral responses to vaccine in peritoneal dialysis. [ABSTRACT FROM AUTHOR]

Background and objectives: Dyslipidemia is one of the most important modifiable risk factors in the pathogenesis of cardiovascular disease in the general population, but its importance in the hemodialysis (HD) population is uncertain. Materials and Methods: This retrospective cohort study includes HD patients hospitalized due to acute coronary syndrome (ACS) in the period 2015–2020 with lipid profile data during ACS. A control group with preserved kidney function was matched. Risk factors for 30-day and 1-year mortality were assessed. Results: Among 349 patients included in the analysis, 246 were HD-dependent ("HD group"). HD group patients had higher prevalence of diabetes, hypertension, and heart disease than the control group. At ACS hospitalization, lipid profile and chronic statin treatment were comparable between groups. Odds ratios for 30-day mortality in HD vs. control group was 5.2 (95% CI 1.8–15; p = 0.002) and for 1-year, 3.4 (95% CI 1.9–6.1; p <0.001). LDL and LDL < 70 did not change 30-day and 1-year mortality rates in the HD group (p = 0.995, 0.823, respectively). However, survival after ACS in HD patients correlated positively with nutritional parameters such as serum albumin (r = 0.368, p < 0.001) and total cholesterol (r = 0.185, p < 0.001), and inversely with the inflammatory markers C-reactive protein (CRP; r = −0.348, p < 0.001) and neutrophils-to-lymphocytes ratio (NLR; r = −0.181, p = 0.019). Multivariate analysis demonstrated that heart failure was the only significant predictor of 1-year mortality (OR 2.8, p = 0.002). LDL < 70 mg/dL at ACS hospitalization did not predict 1-year mortality in the HD group. Conclusions: Despite comparable lipid profiles and statin treatment before and after ACS hospitalization, mortality rates were significantly higher among HD group. While malnutrition–inflammation markers were associated with survival of dialysis patients after ACS, LDL cholesterol was not. Thus, our study results emphasize that better nutritional status and less inflammation are associated with improved survival among HD patients. [ABSTRACT FROM AUTHOR]

Background: Endothelial dysfunction, vascular inflammation and accelerated atherosclerosis have been investigated extensively in patients with chronic kidney disease (CKD). These conditions, as well as protein–energy malnutrition and oxidative stress, impair kidney function and contribute to increased morbidity and mortality among patients with end-stage kidney disease undergoing hemodialysis (HD). TXNIP, a key regulator of oxidative stress, has been linked to inflammation and suppresses eNOS activity. STAT3 activation adds to endothelial cell dysfunction, macrophage polarization, immunity and inflammation. Therefore, it is critically involved in atherosclerosis. This study evaluated the effect of sera from HD patients on the TXNIP-eNOS-STAT3 pathway using an in vitro model of human umbilical vein endothelial cells (HUVECs). Methods: Thirty HD patients with end-stage kidney disease and ten healthy volunteers were recruited. Serum samples were taken at dialysis initiation. HUVECs were treated with HD or healthy serum (10% v/v) for 24 h. Then, cells were collected for mRNA and protein analysis. Results: TXNIP mRNA and protein expression were significantly increased in HUVECs treated with HD serum compared to healthy controls (fold changes: 2.41 ± 1.84 vs. 1.41 ± 0.5 and 2.04 ± 1.16 vs. 0.92 ± 0.29, respectively), as were IL-8 mRNA (fold changes: 2.22 ± 1.09 vs. 0.98 ± 0.64) and STAT3 protein expression (fold changes: 1.31 ± 0.75 vs. 0.57 ± 0.43). The expression of eNOS mRNA and protein (fold changes: 0.64 ± 0.11 vs. 0.95 ± 0.24; 0.56 ± 0.28 vs. 4.35 ± 1.77, respectively) and that of SOCS3 and SIRT1 proteins were decreased. Patients' nutritional status, reflected by their malnutrition–inflammation scores, did not affect these inflammatory markers. Conclusions: This study showed that sera from HD patients stimulated a novel inflammatory pathway, regardless of their nutritional status. [ABSTRACT FROM AUTHOR]

Introduction: The incidence of chronic kidney disease (CKD) is growing rapidly, along with the increasing geriatric population. CKD patients have higher incidence of fractures, stroke, and hospitalizations requiring rehabilitation. This is accompanied with the need for suitable rehabilitation programs to decrease disability and improve functionality to help elderly CKD patients maintain independence in activities of daily living. Considering that survivors of acute kidney injury (AKI) tend to experience decreased quality of life with increased frailty, rehabilitation in the elderly with kidney injury becomes even more complex. The aim of this study was to examine the impact of AKI on the outcomes of rehabilitation among elderly patients with CKD. Methods: For this retrospective, observational study, the electronic medical records of all patients who were hospitalized in the rehabilitation department were reviewed. We assessed functional status at the beginning and end of rehabilitation, renal outcome, and all-cause mortality among elderly patients with CKD who experienced an AKI and compared them to those who did not have an AKI. Results: The study cohort included 183 elderly patients with non-dialysis-dependent CKD. Patients with AKI (23% of study cohort) had a higher prevalence of heart failure and lower baseline estimated glomerular filtration rate, as compared with patients who did not have AKI. They were admitted to rehabilitation at a poorer functional capacity and were also discharged with lower functional independence measure scores. Overall odds ratio for all-cause death among patients with AKI versus without AKI was 3.2 (95% CI: 1.6–6.5; p = 0.001). Conclusion: AKI and CKD are interrelated syndromes. AKI was prevalent among elderly CKD patients and was associated with worse rehabilitation outcomes and higher mortality compared to similar patients without AKI. [ABSTRACT FROM AUTHOR]

Introduction: Arterial calcification is an integral component of active atherosclerosis and is an independent risk factor for cardiovascular disease. Atherosclerosis is a systemic, life‐threating disease that may occur at different sites and in various clinical presentations. Intracranial and valvular calcifications are common among dialysis patients and have been associated with poor cardiovascular outcomes. The aim of this study was to assess the clinical impact of valvular and intracranial arterial calcifications on mortality among chronic hemodialysis patients. Methods: A blinded neuroradiologist graded intracranial calcifications (ICC) of all hemodialysis patients who underwent brain computerized tomography (CT) from 2015 to 2017 in our institution. Valvular calcifications were assessed by echocardiography. Only hemodialysis patients with available echocardiography and brain CT were included. Findings: This study included 119 patients (mean age 70.6 ± 12.6 years, 57.1% men, and mean dialysis vintage 25.8 ± 42.6 months). Among the cohort, 19 (16%) had no cardiac or brain calcifications and 65 (54.6%) had both valvular and intracranial calcifications. Considering the patients with no calcification as the reference group yielded adjusted odds ratios for all‐cause mortality of 3.68 (95%CI 1.55–8.75) among patients with any brain calcifications, p = 0.002. While valvular calcifications alone did not increase the 1‐year mortality rate, ICC was the most important predictor of all‐cause 1‐year mortality in the study cohort. Discussion: We found an independent association between ICC and the risk of death among hemodialysis patients. Assessing ICC may contribute to the risk stratification of hemodialysis patients. These calcifications are no less important than valvular calcifications. [ABSTRACT FROM AUTHOR]

Maintenance hemodialysis (MHD) patients have impaired immunological responses to pathogens and vaccines. In this study, we compared the humoral response to HBV and COVID-19 vaccines in a cohort of MHD patients. Demographic and clinical characteristics of vaccine responders and non-responders were also compared, and the association between the humoral responses to both vaccines was evaluated. The cohort included 94 MHD patients who were vaccinated at least once for HBV and twice for COVID-19. Among the 94 patients, 28 (29.8%) did not develop protective titers to HBV. Hypertension, coronary heart disease, and heart failure were more common in non-responders. Among MHD patients, 85% had positive IgG anti-spike SARS-CoV-2 levels 6 months after two doses of BNT162b2 (Pfizer/Biotech) vaccine. Age and immunosuppressive therapy were the main predictors of humoral response to COVID-19 vaccine. We did not find any association between non-responders to HBV and non-responders to COVID-19 vaccine. There was no difference in IgG anti-spike titers between HBV responders and non-responders (505 ± 644 vs. 504 ± 781, p = 0.9) Our results suggest that reduced humoral response to hepatitis B is not associated with reduced response to COVID-19 vaccine. Different risk-factors were associated with poor immune response to HBV and to COVID-19 vaccines. [ABSTRACT FROM AUTHOR]

Problem: Preeclampsia (PE) and intrauterine growth restriction (IUGR) are leading causes of perinatal complications, affecting 8%–10% of all pregnancies. Inflammasomes are suspected to be one of the mechanisms that lead to the process of term and preterm labors. This study evaluated the inflammasome‐dependent inflammation processes in placental tissue of women with PE and IUGR. Methods of Study: In this prospective cohort study, 14 women with PE, 15 with placental‐related IUGR and 19 with normal pregnancy (NP) were recruited during admission for delivery. Maternal blood was obtained prior to delivery and neonatal cord blood and placental tissue were obtained after delivery. Results: NLRP7 and PYCARD protein expression were higher in placental PE and IUGR samples versus NP samples. Immunostaining revealed that NLRP7 and PYCARD were upregulated in PE and IUGR placental syncytiotrophoblast, stroma and endothelial cells. PYCARD serum levels were significantly higher in women with PE and IUGR. No significant changes were observed in neonatal cord blood. Conclusions: NLRP7 and PYCARD are key inflammatory proteins that are significantly elevated in PE and IUGR. Better understanding their significance may enable them to become markers of prediction or progression of PE and IUGR. [ABSTRACT FROM AUTHOR]

The CHA2DS2-VASc score incorporates several comorbidities which have prognostic implications in COVID-19. We assessed whether a modified score (M-R2CHA2DS2-VASc), which includes pre-admission kidney function and male sex, could be used to classify mortality risk among people hospitalized with COVID-19. This retrospective study included adults admitted for COVID-19 between March and December 2020. Pre-admission glomerular filtration rate (GFR) was calculated based on serum creatinine and used for scoring M-R2CHA2DS2-VASc. Participants were categorized according to the M-R2CHA2DS2-VASc categories as 0–1 (low), 2–3 (intermediate), or ≥ 4 (high), and according to initial COVID-19 severity score. The primary outcome was 30-day mortality rates. Secondary outcomes were mortality rates over time, and rates of mechanical ventilation, hemodynamic support, and renal replacement therapy. Eight hundred hospitalizations met the study criteria. Participants were 55% males, average age was 65.2 ± 17 years. There were similar proportions of subjects across the M-R2CHA2DS2-VASc categories. 30-day mortality was higher in those in higher M-R2CHA2DS2-VASc category and with severe or critical COVID-19 at admission. Subjects in the low, intermediate, and high M-R2CHA2DS2-VASc categories had 30-day mortality rates of 4.7%, 17% and 31%, respectively (p < 0.001). Higher category was also associated with increased need for mechanical ventilation and renal replacement therapy. All-cause 90-day mortality remained significantly associated with M-R2CHA2DS2-VASc. The M-R2CHA2DS2-VASc score is associated with 30-day mortality rates among patients hospitalized with COVID-19, and adds predictive value when combined with initial COVID-19 severity. [ABSTRACT FROM AUTHOR]

The optimal SARS-CoV-2 vaccination schedule in dialysis patients and the potential need for a fourth vaccine dose are debatable. We prospectively assessed the humoral responses to three and four doses of BNT162b2 among dialysis patients. The study included 106 dialysis patients; 60 (56.6%) and 46 (43.4%) received 3 and 4 vaccine doses, respectively. Anti-spike (anti-S) antibody titers significantly increased after the third vaccine dose, followed by a decline, yet still remained higher than all previous measurements. The fourth vaccine dose led to another profound rise in anti-S titers. The absolute increase following the fourth dose correlated with response to the third dose. Infection risk however was similar between patients vaccinated with three or four doses. [ABSTRACT FROM AUTHOR]

Parathyroid hormone (PTH), which is elevated in patients with chronic renal failure, has been shown to participate in the development of vascular calcification. Previous studies have demonstrated that PTH may promote endothelial expressions of proinflammatory parameters. On the basis of these data, we evaluated whether PTH may have an impact on endothelial osteoprotegerin (OPG), a vascular-protective factor which may control vascular calcification. Endothelial cells were stimulated with [10.sup.-12] to [10.sup.-10] mol/l PTH. PKC and PKA are the main cellular pathways of PTH. Inhibitors and activators of PKC or PKA were used to determine whether these signaling pathways are involved in the control of endothelial OPG. PTH induced a decrease in OPG secretion and mRNA expression. Treatment of PTH-stimulated cells by calphostin C (PKC inhibitor) induced a further decrease in OPG secretion, while Rp-cAMP (PKA inhibitor) had no additional effect. In nonstimulated cells, a PKC activator significantly stimulated OPG secretion, while a PKA activator was associated with a decline. These effects were blunted in the presence of calphostin C and Rp-cAMP, respectively. An increase in OPG secretion induced by a PKC activator indicates that the basal OPG secretion is mediated through PKC. The decrease induced by a PKA activator, which is similar to the decrease observed with PTH, suggests that the action of PTH on OPG secretion and mRNA expression may be due to the PKA pathway. endothelial cells

Advanced glycation end products (AGEs), which are elevated in diabetic and uremic patients, may induce vascular dysfunctions, and calcitriol may improve the cardiovascular complications. Therefore, we examined whether calcitriol may modify the endothelial response to AGEs stimulation. Knowing the importance of nuclear factor-[kappa]B in endothelial inflammatory responses, the effect of AGEs and calcitriol on this pathway was also studied. Calcitriol was added to endothelial cells previously incubated with AGE-human serum albumin (HSA). AGE-HSA induced a decrease in endothelial nitric oxide synthase (eNOS) mRNA expression and enzyme activity. Addition of calcitriol to AGE-HSA-treated endothelial cells improved the decreased action of AGEs on the eNOS system. AGE-HSA increased the AGEs receptor mRNA and protein, which were both blunted by calcitriol. The parallel elevation of interleukin-6 mRNA in the presence of AGE-HSA was also blunted by calcitriol. The NF-[kappa]B-p65 DNA binding activity was enhanced and associated with a decrease in inhibitor [kappa]B[alpha] (I[kappa]B[alpha]) and an increase in phosphorylated (p)-I[kappa]B[alpha] levels. Addition of calcitriol blunted the AGEs-induced elevation of NF-[kappa]B-p65 DNA binding activity, a phenomenon related to an increased expression of I[kappa]B[alpha]. This increase was correlated to declined p-I[kappa]B[alpha] levels. The present results support the concept that calcitriol may act as a vascular protective agent counteracting the probable deleterious actions of AGEs on endothelial cell activities. vitamin D; advanced glycation end products; nuclear factor-[kappa]B; endothelial cells

Parathyroid hormone (PTH), the major systemic calcium-regulating hormone, has been linked to uremic vascular changes. Considering the possible deleterious action of PTH on vascular structures, it seemed logical to evaluate the impact of PTH on the receptor of advanced glycation end products (RAGE) and interleukin 6 (IL-6) mRNA and protein expression, taking into account that such parameters might be involved in the pathogenesis of vascular calcification, atherosclerosis, and/or arteriolosclerosis. Human umbilical vein cord endothelial cells (HUVEC) were stimulated for 24 h with [10.sup.-12]-[10.sup.-10] mol/l PTH. The mRNA expression of RAGE and IL-6 was established by reverse transcriptase/PCR techniques. RAGE protein levels were determined by Western blot and IL-6 secretion was measured by ELISA. The pathways by which PTH may have an effect on HUVEC functions were evaluated. PTH ([10.sup.-11]-[10.sup.-10] mol/l) significantly increased RAGE mRNA and protein expression. PTH also significantly increased IL-6 mRNA expression without changes at protein levels. The addition of protein kinase (PKC or PKA) inhibitors or nitric oxide (NO) synthase inhibitors significantly reduced the RAGE and IL-6 mRNA expression and the RAGE protein expression. PTH stimulates the mRNA expressions of RAGE and IL-6 and the protein expression of RAGE. These stimulatory effects are probably through PKC and PKA pathways and are also NO dependent. Such data may explain the possible impact of PTH on the atherosclerotic and arteriosclerotic progression. endothelial cells; IL-6; receptor of advanced glycation end products

Introduction: Coronavirus disease is associated with increased morbidity and mortality in maintenance hemodialysis (MHD) patients. Recent breakthrough infection in vaccinated people has led some authorities to recommend a booster dose for patients fully vaccinated 5–8 months ago. We aimed to assess the humoral response of MHD patients following a booster dose with the BNT162b2 vaccine. Methods: The study included 102 MHD patients vaccinated with 2 doses of the BNT162b2 (Pfizer-BioNTech) vaccine. A third dose (booster) was recommended to all MHD patients in our center and was given to those who opted to receive it, resulting in a booster group and a control group that did not receive the booster. Previous exposure was excluded by testing for the presence of the anti-nucleocapsid antibody (SARS-CoV-2) or positive PCR. We assessed the humoral response before and after the booster dose. Results: Of 66 patients in the booster group, 65 patients (98.5%) developed a positive antibody response, from 472.7 ± 749.5 to 16,336.8 ± 15,397.3, as compared to a sustained decrease in the control group (695.7 ± 642.7 to 383.6 ± 298.6), p < 0.0001. No significant adverse effects were reported. Prior antibody titers were positively correlated to IgG levels following the booster dose. There was a significant association between malnutrition-inflammation markers and the humoral response. Conclusions: Almost all MHD patients developed a substantial humoral response following the booster dose, which was significantly higher than levels reported for MHD patients following administration of 2 doses alone. Further studies and observations are needed to determine the exact timing and dosing schedule. [ABSTRACT FROM AUTHOR]

Brain atrophy (BA) is often found in neuroimaging of hemodialysis patients, representing parenchymal cerebral damage. Likely contributing factors to BA are age, chronic hypertension, diabetes mellitus and other cardiovascular risk factors of atherosclerosis that are also common among hemodialysis patients. BA may also occur due to focal ischemia and hypoperfusion during hemodialysis. However, data on optimal blood pressure (BP) in these patients are limited. The goal of this study was to determine whether the prevalence and severity of BA would be higher among hemodialysis patients with lower BP. A blinded neuroradiologist graded BA of all hemodialysis patients who underwent brain non‐contrast computerized tomography (CT) from 2015 to 2017 in our institution. Age‐ and sex‐matched patients with normal kidney function who underwent brain CT during the same period and technique served as the control group. A total of 280 patients were included in this retrospective study, with average BP of 140/70 mmHg among hemodialysis patients and 142/75 mmHg in the control group. BA was more common in dialysis patients and its severity increased with age and traditional cardiovascular risk factors. We observed a significant negative correlation between diastolic BP (DBP) at dialysis initiation and BA. Average DBP decreased with increasing severity of BA. These findings were observed in both hemodialysis and non‐CKD patients. BA was associated with lower DBP, which may induce cerebral hypoperfusion and ischemia. This finding should discourage over‐treatment of hypertension among hemodialysis patients. [ABSTRACT FROM AUTHOR]

Peritoneal dialysis (PD) causes structural and functional changes in the peritoneal membrane, which are attributed to local inflammatory process. This study assessed the presence of galectin‐3 (Gal‐3), a known inflammatory modulator, in dialysate effluent and correlated its levels with markers of inflammatory process. Gal‐3 levels in serum and dialysate effluent were measured in prevalent PD patients on morning visits (n = 27) or during peritoneal equilibration tests (PET, n = 16), it association with clinical and laboratory parameters, including dialysate/plasma creatinine (D/P creatinine) and interleukin‐6 (IL‐6) levels was analysed. Gal‐3 levels in dialysate effluent correlated with D/P creatinine (0.663, p = 0.005) and dialysate effluent IL‐6 levels (0.674, p = 0.002), but not with serum Gal‐3 levels or dialysis vintage. Patients who were high transporters had higher Gal‐3 levels in dialysate effluent, as compared to lower transporters. In multivariate regression analysis, dialysate IL‐6 level was the strongest predictor of dialysate Gal‐3 levels. This study found Gal‐3 in dialysate effluent correlated with D/P creatinine and dialysate IL‐6 levels. These findings may imply that Gal‐3 has a role in the intraperitoneal inflammatory process. However, this needs to be investigated further. SUMMARY AT A GLANCE: Galectin‐3 (Gal‐3) is an important inflammatory modulator. This study showed that dialysate Gal‐3 levels correlated with peritoneal transport parameters, suggesting that Gal‐3 may play a role in the regulation of peritoneal transport. [ABSTRACT FROM AUTHOR]

Introduction: The prevalence of intracranial arterial calcification (ICAC) in maintenance hemodialysis (MHD) patients is about 90%, and its severity is correlated with age, hemodialysis vintage, and mineral bone disease. Elevated concentrations of calcium and phosphorus are not sufficient for medial calcification because of inhibition by pyrophosphate. Alkaline phosphatase (ALP) promotes calcification by hydrolyzing extracellular pyrophosphate. Epigenetic mechanisms involving ALP inhibition by apabetalone were investigated as a potential target for preventing vascular calcifications (VCs). This study assessed the combined impact of VCs and elevated serum ALP on mortality among chronic HD patients. Methods: VCs represented by ICAC were measured simultaneously with mineral bone disease parameters including serum ALP of MHD patients who underwent noncontrast brain computed tomography from 2015 to 2018 in our institution. Results: This retrospective study included 150 MHD patients (mean age 71.3 ± 12.1 years, 60.1% male). Of the total cohort, 12 (7.8%) had no brain calcifications and 69 (45.1%) had multiple intracranial calcifications. Considering the patients with normal ALP and no calcification as the reference group yielded adjusted odds ratios for all-cause mortality of 4.6 (95% CI: 1.7–12.7) among patients with brain calcifications and normal ALP (p = 0.003) and odds ratios for all-cause mortality of 6.1 (95% CI: 2.1–17.7) among patients with brain calcifications and elevated ALP (p= 0.001). Conclusion: We found an independent association between ICAC and the risk of death among MHD patients. The combined effect of ICAC and elevated ALP was associated with a higher odds ratio for all-cause mortality in MHD patients and may contribute to the risk stratification of these patients. [ABSTRACT FROM AUTHOR]

Background and Aims: Gestational diabetes mellitus (GDM), hyperglycemia diagnosed during pregnancy, is one of the most common medical complications of pregnancy, treated primarily by diet and pharmacotherapy, if indicated. It is well-established that GDM increases the risk of adverse pregnancy outcomes and long-term complications in mothers and infants. Galectin-3 (Gal-3) is important in processes of cell growth, differentiation, inflammation, and fibrosis. We evaluated Gal-3 expression in pregnancies complicated by GDM as a parameter that might explain how GDM influences early onset of future complications.Methods and Results: Forty-four women with GDM and 40 with normal pregnancy (NP) were recruited during delivery admission. Blood samples were obtained from parturients and umbilical cords blood, as well as placental tissue for analysis. Gal-3 mRNA expression was increased in maternal blood samples and placental tissue of women with GDM compared to NP. In GDM, Gal-3 mRNA was decreased in cord blood compared to maternal blood and placental tissue. Gal-3 GDM placental protein expression was increased compared to NP. Immunostaining revealed that Gal-3 is upregulated in GDM placental extravillous trophoblast. ELISA of Gal-3 maternal serum levels between GDM and NP were similar.Conclusion: Gal-3 is strongly expressed at molecular levels (mRNA and protein expression) in GDM maternal blood and placental tissue, and decreased in cord blood. These findings highlight the role of the placenta in protecting the fetus from potential Gal-3 damage. Gal-3 expression at mRNA and protein levels might be influenced by diabetes, even if blood glucose is balanced by medication or diet. [ABSTRACT FROM AUTHOR]

• Addition of renal function may be valuable for risk stratification. • This study included 12,449 low-risk patients with chest pain. • R 2 CHA 2 DS 2 -VASc score predicted acute coronary syndrome and mortality 30 days and 1 year after discharge. Chest-pain patients with no evidence of acute coronary syndrome might still be at risk for adverse outcomes. Adding renal function to the classic scoring of CHADS and CHA 2 DS 2 VASC may improve risk stratification of chest-pain patients discharged from internal medicine wards after acute coronary syndrome (ACS) rule-out. We accessed medical records of patients admitted to internal medicine wards during 2010–2016 and discharged following ACS rule-out. A R 2 CHA 2 DS 2 -VASc score model that included higher scores as kidney function deteriorated was calculated and compared to CHADS and CHA 2 DS 2 VASC scores. The primary endpoint was the composite of 30-day ACS and mortality. One-year ACS and 1-year mortality were the secondary endpoints. The study included 12,449 patients, stratified into three risk groups according to their R 2 CHA 2 DS 2 -VASc score. Participants were stratified into 3 groups according to R 2 CHA 2 DS 2 -VASc score. R 2 CHA 2 DS 2 -VASc score predicted better the composite outcome of ACS and 30-day and 1-year mortality after discharge (OR: 4, 95%, CI 2.3–7, p < 0.01 and OR: 13.3, 95% CI 7.8–22.7, p < 0.01, respectively). Receiver operating characteristic curve analysis showed better risk stratification of the R 2 CHA 2 DS 2 -VASc compared with both CHADS and CHA 2 DS 2 VASC score. The R 2 CHA 2 DS 2 -VASc score is a better predictor of short- and long-term cardiovascular morbidity and mortality after hospital discharge. [ABSTRACT FROM AUTHOR]

• Medical records of ambulatory patients with heart failure were reviewed. • Among 814 patients, 464 (57%) had non-coronary cardiac calcifications. • Patients with calcifications had more hospitalizations for heart failure. • The OR for all-cause death, HF hospitalizations, and the composite endpoint were greater in patients with calcifications. • Calcifications should be included in risk stratification for heart failure. Calcium deposits on heart valves are considered a local manifestation of atherosclerosis and are associated with poor cardiovascular outcomes. The clinical significance of cardiac calcifications among heart failure (HF) patients, as assessed by echocardiography, is unknown. This study evaluated associations of cardiac calcifications with mortality and hospital admissions in this specific population. Medical records of all patients who initiated ambulatory surveillance at our HF clinic during 2011–2018 were reviewed. Calcifications in the aortic valve, aortic root, or the mitral valve were evaluated. Patients with moderate to severe regurgitation or stenosis of the aortic or mitral valves were excluded. The primary endpoint was the composite of long-term all-cause mortality and HF hospitalizations. Secondary endpoints were long-term all-cause mortality and more than one hospitalization due to HF. This retrospective study included 814 patients (mean age 70.9 ± 13 years, 63.2% male). Of the total cohort, 350 (43%) had no cardiac calcifications and 464 (57%) had at least 1 calcified site. Considering the patients with no calcification as the reference group yielded a higher adjusted odds ratios for the composite endpoint, all-cause death, and recurrent HF hospitalizations, among patients with any cardiac calcification (OR = 1.68, 95%CI = 1.1–2.5, p = 0.01, OR=1.61, 95%CI = 1.1–2.3, p < 0.01, and OR = 1.50, 95%CI = 1.1–2.2, p < 0.01, respectively). We found an independent association between cardiac calcifications and the risk of death and HF hospitalizations among ambulatory HF patients. Cardiac calcifications evaluated during routine echocardiography may contribute to the risk stratification of patients with HF. [ABSTRACT FROM AUTHOR]

Background: Predicting the mortality risk of patients un-dergoing hemodialysis (HD) is challenging. Cell-free DNA (cfDNA) is released into circulation from dying cells, and its elevation is predictive of unfavorable outcome. In a pilot study, we found post-HD cfDNA level to be a predictor of all-cause mortality. Thus, the aim of this study was to confirm the prognostic power of cfDNA in a larger prospective cohort study conducted at 2 medical centers. Methods: CfDNA levels were measured by a rapid fluorometric assay on sera obtained before and after 1 HD session. One hundred fifty-three patients were followed up to 46 months for mortality during which time 47 patients died. We compared the predictive value of cfDNA to age, comorbidities, and standard blood tests. Results: Examining standard blood tests, only post-HD cfDNA levels were elevated in the non-survivor group compared to survivors (959 vs. 803 ng/mL, p = 0.04). Pre- and post-HD cfDNA levels correlated with age and diabetes. Patients with elevated cfDNA (>850 ng/mL) showed lower survival than those with normal levels. A Cox proportional hazard regression model demonstrated a significant hazard ratio of 1.92 for post-HD cfDNA levels. Logistic regression models showed that post-HD cfDNA was a significant predictor of mortality at 1–3 years with odd ratios of 4.61, 4.36, and 6.22, respectively. Conclusions: Post-HD cfDNA level was superior to standard blood tests and could serve as a biomarker to assist in decision-making for HD-treated patients. [ABSTRACT FROM AUTHOR]

Background: Patients with end-stage renal disease (ESRD) undergoing chronic hemodialysis are at high mortality and cardiovascular risk. This study was aimed to assess whether the CHA2DS2-VASc score may be used for risk stratification of this population.Methods: Included were patients undergoing chronic hemodialysis at Meir Medical Center. The CHA2DS2-VASc score was calculated for each patient at the initiation of hemodialysis. Patients were classified into 3 groups according to the CHA2DS2-VASc score: 0-3 (low), 4-5 (intermediate), and ≥6 (high). The primary endpoint was the composite of all-cause mortality, myocardial infarction, and stroke during the first year of hemodialysis.Results: Of the 457 patients with ESRD, 181 (40%) had low, 193 (42%) intermediate, and 83 (18%) high CHA2DS2-VASc scores. During the first year of hemodialysis, 109 (23.8%) patients died, 17 (3.7%) had a stroke, and 28 (6.1%) had a myocardial infarction. Compared to patients in the low CHA2DS2-VASc score group, those in the intermediate and high score groups had higher risk for the composite endpoint (OR: 2.6, 95% CI: 1.6-4.2, p < 0.01 and OR: 4.2, 95% CI: 2.3-7.5, p < 0.01, respectively). Each 1-point increase in CHA2DS2-VASc score was associated with a 38% increased risk for the composite endpoint, a 19% increased risk for 1-year myocardial infarction, and a 29% increased risk for 1-year stroke.Conclusions: Patients with ESRD are at an extremely high mortality and cardiovascular risk within the first year of hemodialysis. The CHA2DS2-VASc score was strongly associated with adverse outcomes and may be used for risk stratification of these patients. [ABSTRACT FROM AUTHOR]

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