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Background The association between common carotid artery intima-media thickness (CCA-IMT) and incident carotid plaque has not been characterized fully. We therefore aimed to precisely quantify the relationship between CCA-IMT and carotid plaque development. Methods and Results We undertook an individual participant data meta-analysis of 20 prospective studies from the Proof-ATHERO (Prospective Studies of Atherosclerosis) consortium that recorded baseline CCA-IMT and incident carotid plaque involving 21 494 individuals without a history of cardiovascular disease and without preexisting carotid plaque at baseline. Mean baseline age was 56 years (SD, 9 years), 55% were women, and mean baseline CCA-IMT was 0.71 mm (SD, 0.17 mm). Over a median follow-up of 5.9 years (5th-95th percentile, 1.9-19.0 years), 8278 individuals developed first-ever carotid plaque. We combined study-specific odds ratios (ORs) for incident carotid plaque using random-effects meta-analysis. Baseline CCA-IMT was approximately log-linearly associated with the odds of developing carotid plaque. The age-, sex-, and trial arm-adjusted OR for carotid plaque per SD higher baseline CCA-IMT was 1.40 (95% CI, 1.31-1.50; I 2 =63.9%). The corresponding OR that was further adjusted for ethnicity, smoking, diabetes, body mass index, systolic blood pressure, low- and high-density lipoprotein cholesterol, and lipid-lowering and antihypertensive medication was 1.34 (95% CI, 1.24-1.45; I 2 =59.4%; 14 studies; 16 297 participants; 6381 incident plaques). We observed no significant effect modification across clinically relevant subgroups. Sensitivity analysis restricted to studies defining plaque as focal thickening yielded a comparable OR (1.38 [95% CI, 1.29-1.47]; I 2 =57.1%; 14 studies; 17 352 participants; 6991 incident plaques). Conclusions Our large-scale individual participant data meta-analysis demonstrated that CCA-IMT is associated with the long-term risk of developing first-ever carotid plaque, independent of traditional cardiovascular risk factors.

Background: To quantify the association between effects of interventions on carotid intima-media thickness (cIMT) progression and their effects on cardiovascular disease (CVD) risk., Methods: We systematically collated data from randomized, controlled trials. cIMT was assessed as the mean value at the common-carotid-artery; if unavailable, the maximum value at the common-carotid-artery or other cIMT measures were used. The primary outcome was a combined CVD end point defined as myocardial infarction, stroke, revascularization procedures, or fatal CVD. We estimated intervention effects on cIMT progression and incident CVD for each trial, before relating the 2 using a Bayesian meta-regression approach., Results: We analyzed data of 119 randomized, controlled trials involving 100 667 patients (mean age 62 years, 42% female). Over an average follow-up of 3.7 years, 12 038 patients developed the combined CVD end point. Across all interventions, each 10 μm/y reduction of cIMT progression resulted in a relative risk for CVD of 0.91 (95% Credible Interval, 0.87-0.94), with an additional relative risk for CVD of 0.92 (0.87-0.97) being achieved independent of cIMT progression. Taken together, we estimated that interventions reducing cIMT progression by 10, 20, 30, or 40 μm/y would yield relative risks of 0.84 (0.75-0.93), 0.76 (0.67-0.85), 0.69 (0.59-0.79), or 0.63 (0.52-0.74), respectively. Results were similar when grouping trials by type of intervention, time of conduct, time to ultrasound follow-up, availability of individual-participant data, primary versus secondary prevention trials, type of cIMT measurement, and proportion of female patients., Conclusions: The extent of intervention effects on cIMT progression predicted the degree of CVD risk reduction. This provides a missing link supporting the usefulness of cIMT progression as a surrogate marker for CVD risk in clinical trials.

Atherosclerosis - the pathophysiological mechanism shared by most cardiovascular diseases - can be directly or indirectly assessed by a variety of clinical tests including measurement of carotid intima-media thickness, carotid plaque, -ankle-brachial index, pulse wave velocity, and coronary -artery calcium. The Prospective Studies of Atherosclerosis -(Proof-ATHERO) consortium (https://clinicalepi.i-med.ac.at/research/proof-athero/) collates de-identified individual-participant data of studies with information on atherosclerosis measures, risk factors for cardiovascular disease, and incidence of cardiovascular diseases. It currently comprises 74 studies that involve 106,846 participants from 25 countries and over 40 cities. In summary, 21 studies recruited participants from the general population (n = 67,784), 16 from high-risk populations (n = 22,677), and 37 as part of clinical trials (n = 16,385). Baseline years of contributing studies range from April 1980 to July 2014; the latest follow-up was until June 2019. Mean age at baseline was 59 years (standard deviation: 10) and 50% were female. Over a total of 830,619 person-years of follow-up, 17,270 incident cardiovascular events (including coronary heart disease and stroke) and 13,270 deaths were recorded, corresponding to cumulative incidences of 2.1% and 1.6% per annum, respectively. The consortium is coordinated by the Clinical Epidemiology Team at the Medical University of Innsbruck, Austria. Contributing studies undergo a detailed data cleaning and harmonisation procedure before being incorporated in the Proof-ATHERO central database. Statistical analyses are being conducted according to pre-defined analysis plans and use established methods for individual-participant data meta-analysis. Capitalising on its large sample size, the multi-institutional collaborative Proof-ATHERO consortium aims to better characterise, understand, and predict the development of atherosclerosis and its clinical consequences., (© 2020 S. Karger AG, Basel.)

Background: The aim of this study was to compare the clinical and histopathological course of HCV infection acquired before and during or after renal transplantation., Methods: According to HCV status, 197 RT patients were divided into three groups. At the time of RT, anti-HCV antibody was positive in 47 patients (pre-RT HCV group). In 27 patients, in whom anti-HCV negative at the time of RT, anti-HCV and/or HCV RNA was found to be positive following an ALT elevation episode after RT (post-RT HCV group). Both anti-HCV and HCV RNA were negative at all times in remaining 123 patients (control group)., Results: Liver biopsy was performed in 31 of 47 patients in pre-RT and 24 of 27 in post-RT HCV group after RT. Duration of follow-up was similar in all groups with a mean of 7.1 +/- 4.0 yr. Ascites and encephalopathy were seen in only post-RT HCV group (22%). Histological grade (6.5 +/- 2.7 vs. 4.1 +/- 1.4) and stage (2.0 +/- 1.5 vs. 0.8 +/- 0.8) was significantly severe in post-RT HCV group (p < 0.01). Three patients died due to liver failure in post-RT HCV group., Conclusions: HCV infection acquired during or after RT shows a severe and rapidly progressive clinicopathological course, which is significantly different from pre-transplant anti-HCV positive patients.

The aim of this study was to evaluate the response of tuberculin skin test (TST) and the parameters that affect the response in patients with chronic renal failure (CRF) on different treatment regimens. The study population consisted of 150 patients (78 females, mean age 48.1 + or - 16.7 years, the mean disease duration 6.6 + or - 6.1 years). Of these patients, 50 were on haemodialysis (HD), 50 were renal transplant patients, 26 were on peritoneal dialysis (PD) and 24 were treated medically. TST was performed to all patients, an induration with a diameter of 10 mm or more was accepted as positive response in HD, PD, medical treatment groups, whereas 5 mm or more was considered as positive in transplant group. TST was positive in 52% of the study population (56% in HD group, 54% in PD group, 44% in transplant group, 58% in medical treatment group, p> 0.05). There was a positive correlation between TST and age in patients older than 60 of transplant and medical treatment groups (p= 0.008). In HD patients with negative TST, the number of female patients was higher (p= 0.02). In transplant patients with positive TST, duration of HD was shorter (p= 0.01), the blood urea level was lower (p= 0.04), hemoglobin level was higher (p= 0.04). The ratio of negative TST was higher (p< 0.05), TST reactivity was smaller (p= 0.01) in only transplant patients with no BCG scar. The number of BCG scar was correlated positively with TST (p= 0.04). In the medical treatment group, patients with positive TST response were older (p= 0.02) and in PD group the tuberculin reactivity was not affected by any of the patient-related parameters. It must be considered that the response to TST is low in young patients with uncontrolled CRF and under immunosuppressive therapy.

Some patients with end-stage renal disease suffer severe cardiac dilatation with functional disturbances, notably low ejection fraction (EF) and valvular regurgitation. They often have normal or low blood pressure, and tolerate ultrafiltration (UF) poorly. The aim of our study was to investigate to what extent this condition can still be improved by persistent slow UF. Twelve patients with cardiothoracic index >0.54 and EF <0.45 but otherwise uncomplicated were treated by slow, prolonged UF during hemodialysis (3 times a week) sessions, if necessary supplemented by isolated UF sessions on a separate day. Repeated chest X-rays and Doppler echocardiography were applied. During treatment periods varying from 20 to 120 days, all of the patients lost weight (12+/-10 kg) and became edema free. Cardiothoracic index decreased in all patients from a mean of 0.59+/-0.04 to 0.47+/-0.03. Blood pressure decreased when it had been elevated and increased when it was below normal. Ejection fraction increased in all of them from a mean of 0.31+/-0.9 to 0.50+/-0.9. Mitral and tricuspid regurgitation were found in every patient and disappeared or improved in all of them. Striking improvement of cardiac dilatation and dysfunction can be achieved by carefully monitored persistent UF in the majority of patients with seemingly intractable dilated cardiomyopathy.

As anergy is common in patients with chronic renal failure (CRF), the use of tuberculin skin test (TST) is controversial. Therefore, determination of the factors that affect the TST reactivity would increase the diagnostic value of the test. The aim of the present study was to investigate the factors affecting TST reactivity and evaluate the relationship between T-lymphocyte subsets and TST reactivity. We thus examined 44 patients (mean age 46.6 +/- 15.6 years, 25 males, duration of CRF 5.6 +/- 5.2 years), performed TST (an induration with a diameter of 5 mm or more was considered as positive) and measured Tlymphocyte subsets and biochemical parameters. Twenty-three patients were on hemodialysis, six were on peritoneal dialysis, seven were transplant recipients, and eight were on medical treatment. Eleven patients (25%) had immunosuppressive treatment. Eleven patients (25%) had two, 29 patients (66%) had one, and four patients (9%) had no BCG scars. Five patients (11%) had low body mass index (BMI). T-lymphocyte subsets were as follows: CD4= 40.7 +/- 7.6%, CD8= 32 +/- 8.9%, CD4/CD8= 1.7 +/- 2.5%, CD3= 71.4 +/- 9.4%, CD19= 6.3 +/- 5.1%, NK= 9.7 +/- 5.9. Twenty-two patients had positive TST reactivity. No relation was found between TST reactivity and age, gender, co-morbidity, BCG vaccination, BMI, immunosuppressive therapy, duration and treatment of CRF. Similarly, TST reactivity was not related to the biochemical parameters and Tlymphocyte subsets. These data provide that tuberculin reactivity does not seem to be associated with T-lymphocyte dysfunction and clinical features in patients with chronic renal failure.

Background: It has been claimed that patients with late transplant failure returning to peritoneal dialysis have lower patient and technique survival., Purpose: In this retrospective study, we aimed to clarify this issue in a large PD population., Methods: Thirty-four PD patients with a failed renal transplant (FTx) and 82 PD patients who had never received a kidney transplant (Non-Tx) or HD treatment were investigated. All fTx patients were using only steroids (5-10 mg/day) for first 3 months of peritoneal dialysis. The groups were similar regarding to age, sex, residual renal function and KT/V; none of them was diabetic., Results: Ftx group had a higher number of peritonitis attack than Non-Tx group (2.42 +/- 0.41 v 1.61 +/- 0.15, attack per patient, p = 0.013). PET status was not different. One, 3 and 5 year patient survival calculated with the Kaplan Meier method were 93%; 93%; 93% respectively in Ftx and 97%; 89%; 82% respectively in Non-Tx patients. Technique survival was 83%; 77%; 60% in Ftx and 91%; 64%; 48% in Non-Tx patients respectively., Conclusions: We conclude that PD appears to be a good option for fTx patients. A previous renal transplantation does not adversely affect patient and technique survival. Although the somewhat higher infection risk is of some concern, we did not observe earlier loss of peritoneal functions (high transporter) in the post transplant patients.

In this study, active human herpesvirus (HHV)-6 infection were investigated in 39 renal and 9 bone marrow/stem cell transplant recipients. For this purpose, the presence of HHV-6 DNA in patients sera have been searched by nested polymerase chain reaction (nPCR). In addition, HHV-6 IgM and IgG antibodies were performed by micro-enzyme immunoassay (EIA) to detect seronegative patients before transplantation and IgM response in active or primary HHV-6 infection. Active infection with HHV-6 DNA positivity was detected in 5.3% of renal and 22.2% of bone marrow/stem cell transplant recipients. Active HHV-6 infection was found to be related with asymptomatic reactivation, graft disfunction and cytomegalovirus disease in renal transplant recipients, and, fever and graft versus host disease in bone marrow/stem cell transplant recipients. It has been concluded that, the investigation of HHV-6 DNA by nPCR in the transplant sera, was a practical and useful method for the laboratories, in order to diagnose active HHV-6 infection, while HHV-6 IgG antibody detection was also useful for the differential diagnosis of primary infection or reactivation/reinfection, but HHV-6 IgM antibodies has low value to detect active HHV-6 infection.

Background: The aim of this study was to investigate retrospectively the clinical presentation, the efficacy of reducing immunosuppression and the consequences of this therapeutic approach in Kaposi's sarcoma (KS) developing after renal transplantation., Methods: We reviewed the records of 502 patients who had been followed up at our transplantation unit between October 1, 1987 and December 30, 1998. Twelve patients (2.4%) with KS were included in the study., Results: The mean age of KS patients was 38+/-11 years (one female, 11 males). All were on prednisone, azathioprine (AZT) and cylcosporin treatment. KS was encountered at a mean of 18+/-10 months post-renal transplantation. Typical Kaposi's lesions were present in the skin of 11 out of l2 patients. In the only patient without skin involvement, who died from haemophagocytic histiocytic syndrome caused by septicaemia, KS was diagnosed post-mortem in a lymph node. In five patients only skin involvement was present, while the others also had visceral involvement (oropharynx in two patients, trachea and lung in three, lymph node in two, stomach and duodenum in two). Cyclosporin was stopped within 1 month after KS diagnosis, and AZT was stopped in three patients. Both cutaneous and visceral KS manifestations disappeared and no patient was lost due to KS. During a follow-up period 46+/-19 months, KS recurred in the lungs in one patient together with lung tuberculosis, while he was on prednisone and AZT. Two patients lost their graft due to chronic rejection. The remaining eight patients currently have a functioning graft with a mean creatinine level of 1.4+/-0.5 mg/dl., Conclusion: KS is the most frequent post-transplant neoplasia (80%) in our country. In the present study cohort, half of the patients had visceral involvement. Reduction or discontinuation of immunosuppression caused complete remission in all patients without surgical intervention, chemotherapy or radiotherapy.