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While there is evidence of the presence of the coronavirus in the kidneys and resultant acute kidney injury (AKI), information on the effect of chronic kidney disease (CKD) on COVID-19 outcomes and its pathogenesis is currently lacking.This retrospective, observational study evaluated the outcomes of all consecutive patients hospitalized during COVID-19 outbreaks in Meir Medical Center. Serum creatinine level was assessed before hospitalization ("baseline serum creatinine") and at admission, as well as minimum and maximum serum creatinine levels during hospitalization.Among 658 patients, 152 had eGFR 60 ml/min (termed the CKD group), 506 patients served as controls. Patients in the CKD group were older, with higher prevalence of hypertension, diabetes mellitus and atherosclerosis. Disease severity and clinical presentation of CKD group were comparable to that of control group. Odds ratio for AKI was 5.8 (95%CI 3.8-8.7; p 0.001) in CKD group vs. control group and 3.4 (95%CI 1.1-10.8) for renal replacement therapy (p 0.026). Among the CKD group, 32.2% died after COVID-19 infection versus 14.8% of the controls (p 0.001). Mortality increased as CKD stage increased (14.8% in controls, 29.6% in CKD stage 3, and 39.3% in CKD stages 4 and 5, p 0.001).Despite comparable disease severity at presentation, patients with CKD had significantly more AKI events and required more renal replacement therapy during hospitalization than control patients did. Mortality increased as CKD stage increased.

Background 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 CHA2DS2 VASC may improve risk stratification of chest-pain patients discharged from internal medicine wards after acute coronary syndrome (ACS) rule-out. Methods We accessed medical records of patients admitted to internal medicine wards during 2010–2016 and discharged following ACS rule-out. A R2CHA2DS2-VASc score model that included higher scores as kidney function deteriorated was calculated and compared to CHADS and CHA2DS2 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 R2CHA2DS2-VASc score. Results Participants were stratified into 3 groups according to R2CHA2DS2-VASc score. R2CHA2DS2-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 Conclusions The R2CHA2DS2-VASc score is a better predictor of short- and long-term cardiovascular morbidity and mortality after hospital discharge.

Background 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. Methods 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. Results 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 Conclusions 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.

Background: Red blood cell distribution width (RDW) is a measure of the degree of heterogeneity of erythrocyte volume. Higher RDW levels are associated with increased mortality among patients with ...

Background Assessment of chest pain is one of the most common reasons for hospital admissions in internal medicine wards. However, little is known regarding predictors for poor prognosis in patients discharged from internal medicine wards after acute coronary syndrome (ACS) rule-out. Objective To assess the association of kidney function with mortality and hospital admissions due to ACS in patients with chest pain who were discharged from internal medicine wards following ACS rule-out. Methods Included were patients admitted to an internal medicine ward who were subsequently discharged following an ACSrule-out during 2010–2016. The primary endpoint was the composite of all-cause mortality and hospital admission due to ACS at 30-days following hospital discharge. Results Included in the study were12,337 patients who were divided into 3 groups according to renal function. Considering patients with an eGFR ≥ 60 ml/min/1.73m2 as the reference group yielded adjusted hazard ratios for the composite of 30-day all-cause mortality and hospital admission for ACS that increased with reduced eGFR (HR = 2, 95%CI = 1.3–3.3, HR = 4.8, 95%CI = 3–7.6, for patients with eGFR of 45 to 59.9 or Conclusion We found an independent graded association between lower eGFR and the risk of death and ACS among patients with chest pain who were discharged from internal medicine wards following an ACS rule-out. The eGFR may be combined in the risk stratification of patients with chest pain.

Background Chest-pain patients deemed safe for discharge from internal medicine wards might still be at risk for adverse outcomes. Hypothesis CHA2 DS2 -VASc score improves risk stratification of low-risk chest-pain patients discharged after acute coronary syndrome (ACS) rule-out. Methods We accessed medical records of patients who were admitted to internal medicine wards at a single medical center during 2010-2016 and discharged following an ACS rule-out. Patients were classified according to CHA2 DS2 -VASc score: 0-1 (low), 2-3 (intermediate), >3 (high). Primary endpoint was occurrence of ACS at 1 year; 30-day and 1-year all-cause mortality (ACM) were secondary outcomes. Results Of 12 449 patients, 7057 (57%) had low, 3781 (30%) intermediate, and 1611 (13%) high CHA2 DS2 -VASc scores. Compared with a low score, intermediate and high scores were associated with significantly increased risk for 1-year ACS during the first year (OR: 2.89, 95% CI: 1.91-4.37, P Conclusions High CHA2 DS2 -VASc score (>3) was associated with adverse outcomes among chest-pain patients discharged from internal medicine wards following ACS rule-out.

Magnesium is an essential intracellular cation. Magnesium deficiency is common in the general population and its prevalence among patients with cirrhosis is even higher. Correlation between serum levels and total body content is poor because most magnesium is intracellular. Minimal hepatic encephalopathy is a subclinical phase of hepatic encephalopathy with no overt symptoms. Cognitive exams can reveal minor changes in coordination, attention, and visuomotor function, whereas language and verbal intelligence are usually relatively spared.To assess the correlation between intracellular and serum magnesium levels and minimal hepatic encephalopathy.Outpatients with a diagnosis of compensated liver cirrhosis were enrolled in this randomized, double-blinded study. Patients were recruited for the study from November 2013 to January 2014, and were randomly assigned to a control (placebo) or an interventional (treated with magnesium oxide) group. Serum and intracellular magnesium levels were measured at enrollment and at the end of the study. Cognitive function was assessed by a specialized occupational therapist.Forty-two patients met the inclusion criteria, 29 of whom were included in this study. Among these, 83% had abnormal cognitive exam results compatible with minimal hepatic encephalopathy. While only 10% had hypomagnesemia, 33.3% had low levels of intracellular magnesium. Initial intracellular and serum magnesium levels positively correlated with cognitive performance.Magnesium deficiency is common among patients with compensated liver cirrhosis. We found an association between magnesium deficiency and impairment in several cognitive function tests. This finding suggests involvement of magnesium in the pathophysiology of minimal hepatic encephalopathy.

Shortened telomeres were found in patients with cirrhosis, probably reflecting chronic liver injury, continuous regeneration, and destruction of hepatic nodules.To test whether telomere shortening is a general marker of cirrhosis, independent of disease etiology.We evaluated telomere length in patients with cryptogenic cirrhosis (largely a late sequela of steatohepatitis) compared to patients with cirrhosis caused by chronic hepatitis B and C (HBV/HCV). We also evaluated telomere aggregates, a sensitive parameter of telomere dysfunction and genetic instability. We analyzed peripheral lymphocytes from 25 patients with cryptogenic cirrhosis, 15 patients with cirrhosis due to chronic viral hepatitis, and 20 age-matched controls. Telomere length was analyzed using quantitative fluorescence in situ hybridization. Aggregate size was divided into three fusion groups of 2-5, 6-10, and 11-15 telomeres, relative to the size of a single telomere.Shorter telomere length was found in patients with cirrhosis from all three etiologies (mean 121.3 ± 24.1) compared to controls (mean 63.5 ± 23.5). In contrast, there was significantly more fusion of5 telomeres only in the HBV/HCV cirrhosis group compared to healthy controls (P = 0.023), but not in the cryptogenic cirrhosis group.While shortened telomeres in peripheral lymphocytes are a general marker of liver cirrhosis, telomere aggregates may signify a more sensitive genetic instability parameter for the diverse, etiology-based malignant potential of cirrhosis. This finding is in agreement with the well-known higher tendency toward developing hepatocellular carcinoma with cirrhosis caused by chronic hepatitis relative to steatohepatitis.

Background and aims Primary sclerosing cholangitis and inflammatory bowel disease are two associated, chronic inflammatory, pre-malignant conditions. We hypothesized that patients with these disorders may harbour telomere dysfunction as a marker of chromosomal instability. The aim of our study was to compare parameters of the telomere-telomerase system in these cohorts. Methods In this prospective study, peripheral blood was withdrawn from patients with primary sclerosing cholangitis (N = 20), inflammatory bowel disease (N = 20) and healthy controls (N = 20), and lymphocytes were isolated. Telomere length was quantified as a function of the signal intensity and telomere number. Random aneuploidy and telomere capture were determined by fluorescence in situ hybridization technique with specific probes. Results Patients with inflammatory bowel disease had higher measures of intestinal disease activity than patients with primary sclerosing cholangitis. Despite this, shorter telomere length and telomere aggregates, especially the fusion of 2–5 telomeres, were observed at significantly higher rate in patients with primary sclerosing cholangitis relative to inflammatory bowel disease or healthy controls. Rates of aneuploidy and telomere capture were higher in the two probes in both diseases compared to controls (p Conclusion Dysfunction of telomeres was demonstrated in primary sclerosing cholangitis patients more than inflammatory bowel disease and healthy controls patients, which attests to genetic instability and immunosenescence. Trial registration number NCT02247622 .

Primary sclerosing cholangitis (PSC) and inflammatory bowel disease (IBD) are associated chronic inflammatory diseases with malignant potential. Loss of replication synchrony during the S-phase of the cell cycle has been shown to be linked to several malignant and premalignant states. This study evaluated temporal differences in replication timing between these diseases. The replication pattern of peripheral blood lymphocytes obtained from patients with PSC and IBD and healthy individuals was analyzed by fluorescence in situ hybridization (FISH) in 2 pairs of alleles, in 15qter and 13qter. Asynchrony was determined by the presence of 1 single and 1 set of double dots in the same cell. Samples from subjects with PSC showed significantly greater temporal differences in replication timing, in contrast to the high level of synchrony observed in samples from healthy individuals (p = 0.045). Samples from IBD patients exhibited a nonsignificant increase in replication asynchrony. We believe that these results reflect impairment in the replication control of structural homologous loci in PSC, and that this phenomenon may be correlated with the inflammation-induced malignant potential of this condition.

Background/aims Non-alcoholic fatty liver disease (NAFLD) and cryptogenic cirrhosis (CC), which is largely a late sequela of NAFLD, are considered pre-neoplastic conditions that might progress to hepatocellular carcinoma. Aneuploidy, telomere aggregates and synchronization of replication were evaluated as markers of genetic instability in these patients. Methodology Peripheral blood lymphocytes from 22 patients with NAFLD, 20 patients with CC and 20 age-matched healthy controls were analyzed. To determine random aneuploidy, we used the fluorescence in situ hybridization (FISH) with probes for chromosomes 9 and 18. The rate of aneuploidy was inferred from the fraction of cells revealing one, three or more hybridization signals per cell. Aggregate size was divided into three fusion groups of 2–5, 6–10 and 11–15 telomeres, relative to the size of a single telomere. The replication pattern was determined by FISH in two pairs of alleles, 15qter and 13qter. Asynchrony was determined by the presence of one single and one set of double dots in the same cell. Results Significantly higher random aneuploidy rate was found in the CC patients than in the control group, and to a lesser degree in NAFLD patients. Telomere aggregates were insignificantly higher in both groups. Only patients with CC showed significantly higher rate of asynchronous replication with proportionately more cells with two single dots among the normal cells (p Conclusions These results likely reflect changes in gene replication and cell cycle progression in these conditions, possibly correlating with their malignant potential.

Objective Individuals with chromosomal aneuploidies tend to develop malignancies. Telomerase is an enzyme complex that lengthens telomeres and has enhanced expression in numerous malignancies; one of its components is encoded by the TERC gene. In this study, we evaluated the TERC gene copy number in amniocytes from fetuses with aneuploidy, other than trisomy-21. Methods In this prospective, basic research study, fluorescence in situ hybridization (FISH) for the TERC gene (3q26) was applied to amniocytes retrieved from 14 fetuses with various aneuploidies and from a control group of 6 fetuses with a normal karyotype, to determine the TERC gene copy number. Results The percentage of cells with more than two copies of the TERC gene was lowest in the control group (x3 = 1.2 ± 0.4%; x4 = 0 ± 0%), higher in the sex chromosome aneuploidies (x3 = 4 ± 3%; x4 = 0.7 ± 0.95%) and even higher in trisomy 18 (x3 = 10.6 ± 2.3; x4 = 4.6 ± 1.8). The differences were statistically significant (P Conclusion The TERC gene copy number is increased in aneuploid amniocytes, which demonstrates their genetic instability and is presumably related to their tendency to develop malignancies.

Telomeres are specific repetitive DNA sequences that cap and stabilize the ends of chromosomes. Functional telomeres are essential for the normal segregation and maintenance of chromosomes during mitotic and meiotic division. Pre-eclampsia, a pregnancy-specific syndrome of increased blood pressure accompanied by proteinuria, is often associated with growth deficiency in the fetus. Oxidative stress is a major component in the pathophysiology of pre-eclampsia. In contrast to the nonoverlapping nature of telomeres in normal nuclei, telomeres of tumor nuclei tend to form aggregates (TAs) in various numbers and sizes. The formation of TAs represents a stress-related process and is independent of telomere length and telomerase activity. The aim of this study was to evaluate TA formation in paraffin-embedded placentas from pregnancies complicated with pre-eclampsia (study group), compared with placentas from normal pregnancies (control group). There were significantly more TAs in the study group (mean, 8.00 TAs per case) than in the control group (mean, 2.36 TAs per case) (P < 0.01). Pre-eclampsia-related stress may accelerate apoptosis and cell death and lead to placental dysfunction. TAs formation, which has been linked to stress and tumorgenesis is increased in placentas of pre-eclamptic patients.

Telomeres of tumor nuclei tend to form aggregates (TA). The aim of this study was to estimate the TA formation in leukocytes of patients with chronic hepatitis C (HCV) which is considered to be premalignant disease, in patients of HCV who eradicated the virus. PNA Telomere kit (Dako) was used to evaluate the TA formation with the utilization of 2D fluorescence microscopy. A higher rate of TA was found in both HCV groups as compared to controls. Our results indicate that HCV patients have some of the components that create the cascade of events leading to malignancies.

We report a patient with chronic hepatitis B infection who developed lymphoma and was treated with concomitant cytotoxic and antiviral therapy. In contrast to the expected life threatening fulminant hepatitis that is often reported in this clinical setting, in our patient normalization of liver function tests with temporary loss of viral replication markers were seen. The implications of this rare clinical and serological course are discussed.

Telomeres are nucleoprotein structures located at the termini of chromosomes that protect the chromosomes from fusion and degradation. Hepatocyte cell-cycle turnover may be a primary mechanism of telomere shortening in hepatitis C virus (HCV) infection, inducing fibrosis and cellular senescence. HCV infection has been recognized as potential cause of B-cell lymphoma and hepatocellular carcinoma. The present study sought to assess relative telomere length in leukocytes from patients with chronic HCV infection, patients after eradication of HCV infection (in remission), and healthy controls. A novel method of manual evaluation was applied. Leukocytes derived from 22 patients with chronic HCV infection and age- and sex-matched patients in remission and healthy control subjects were subjected to a fluorescence-in-situ protocol (DAKO) to determine telomere fluorescence intensity and number. The relative, manual, analysis of telomere length was validated against findings on applied spectral imaging (ASI) in a random sample of study and control subjects. Leukocytes from patients with chronic HCV infection had shorter telomeres than leukocytes from patients in remission and healthy controls. On statistical analysis, more cells with low signal intensity on telomere FISH had shorter telomeres whereas more cells with high signal intensity had longer telomeres. The findings were corroborated by the ASI telomere software. Telomere shortening in leukocytes from patients with active HCV infection is probably due to the lower overall telomere level rather than higher cell cycle turnover. Manual evaluation is an accurate and valid method of assessing relative telomere length between patients with chronic HCV infection and healthy subjects.