Evaluation of sexual function and sexual quality of life in women during the COVID-19 Pandemic: the Turkish case.

Background: Sexual health is an important component of general health. Objective: To evaluate sexual function and sexual quality of life (SQOL) in women during the COVID-19 pandemic. Methods: This descriptive, cross-sectional study was conducted in Turkey. Data were collected via a Visual Analog Scale (VAS), Female Sexual Function Index (FSFI), and Sexual Quality of Life-Female (SQOL-F) questionnaire. Results: The mean FSFI score was 26.91±5.62, and 39.1% of the women had an FSFI score of 26.55 or lower. The mean SQOL-F score was 79.08±20.90. FSFI score was significantly associated with employment status (ß=-0.661), partner education (ß=1.698), sexual compatibility between partners (ß=0.518), sexual satisfaction (ß=0.230), fatigue level (ß= -0.120), and frequency of sexual intercourse (ß=0.160). In addition, SQOL-F score was significantly associated with sexual desire (ß=2.625), satisfaction (ß=1.338), pain or discomfort (ß=1.274), age (ß= -0.356), sexual compatibility between partners (ß=1.984), and fatigue level (ß=-0.981) (p<0.05). Conclusion: Less than half of the women participating in this study had sexual dysfunction, and overall SQOL was moderate to high. These results were associated with some descriptive characteristics of the women and were similar to those reported in pre-pandemic studies conducted in Turkey.

Assessment the effect of diabetes education on self-care behaviors and glycemic control in the Turkey Nursing Diabetes Education Evaluating Project (TURNUDEP): a multi-center study.

BACKGROUND: Diabetes education in Turkey is provided by diabetes nurse educators in almost all healthcare organizations. However, the education is not standardized in terms of learning content, duration, and methods. This multi-center study was performed to assess the self-care behaviors and glycemic control following education provided to the patients with type 2 diabetes mellitus by diabetes nurse educators. METHODS: This was a descriptive and cross-sectional study and included 1535 patients admitted to 28 public hospitals for the treatment of type 2 diabetes mellitus. The education was assessed by using a Patient Identification Form and Self-care Scale. RESULTS: The proportion of individuals who received diabetes education within the last year was 78.5%, with 46.7% of them having received it once. Of the patients, 84.8% reported that they received diabetes education individually. It was found that the proportion of individuals who received education about oral antidiabetics (78.5%) and glucose testing at home (78.5%) was higher than the proportion of individuals who received education about exercise (58.8%) and foot care (61.6%). The status of diabetes education, education intervals, and the correlation of the education method with self-care and glycemic control was evaluated. Self-care and glycemic control levels were better among the patients who received diabetes education thrice or more and in patients who received education both individually and in a group (p < 0.05). CONCLUSIONS: Approximately three-quarters of individuals with type 2 diabetes mellitus received education by diabetes nurse educators in Turkey. Diabetes education is positively correlated with self-care and glycemic control levels among patients with type 2 diabetes mellitus. Efforts for generalization and standardized education for all diabetes patients are necessary.

Alexithymia in diabetes patients: its relationship with perceived social support and glycaemic control.

AIM AND OBJECTIVE: This study was conducted to assess whether there is an association between alexithymia in patients with diabetes and the levels of perceived social support and glycaemic control. BACKGROUND: In the literature, whether inadequate perceived social support is a cause or effect of alexithymia has also not been clearly explained. It is stated that it is difficult to determine from where these contradictions arise, and there is a need for more studies on this topic. METHOD: This cross-sectional and correlational study included 537 patients with type I and type 2 diabetes. The data were collected using a Patient Information Form including the patient's HbA1c value that reflected their glycaemic control level, the Toronto Alexithymia Scale and the Multidimensional Scale of Perceived Social Support. The study was reported according to the STROBE Declaration. RESULTS: Among the patients with diabetes, 63.9% showed signs of alexithymia. Alexithymia had a negative relationship with perceived social support and a positive relationship with HbA1c. Additionally, it was determined that the patients who showed signs of alexithymia had lower levels of perceived social support in comparison with those who did not show such signs, whereas the HbA1c levels of the former were also higher than those of the latter. Moreover, it was found that the duration of the disease, HbA1c levels and levels of perceived social support from family and a significant other explained 30% of the total variance in the level of alexithymia. CONCLUSION: Alexithymia was seen prevalently among the patients with diabetes, and it was associated with a reduced level of perceived social support and weak glycaemic control. RELEVANCE TO CLINICAL PRACTICE: It is recommended to provide patients with psychosocial support in the scope of holistic care and include the individuals who provide care for and support the patient in the patient's management of the disease.

The evolving role of drug-coated balloons for the treatment of complex femoropopliteal lesions.

Conventional therapies for transcatheter treatment of patients with infrainguinal obstructive disease remain compromised by high restenosis rates. Drug-coated balloons (DCB) offer a novel therapeutic alternative targeting the source of neo-intimal hyperplasia, without the need for a permanent endovascular scaffold and their inherent limitations. A systematic research of the medical databases (Pubmed) has been conducted for this up-to-date review. Key words, such as "drug-coated balloons" (DCB), "drug-eluting balloon," "in-stent-restenosis" (ISR), "de-novo stenosis," "plain old angioplasty," "atherectomy," "debulking," "superficial femoral artery," "popliteal artery," "above/below the knee," and "peripheral artery disease" have been used for literature search. Furthermore, data from reviews, original contributions, randomized controlled studies, observational studies, registries and single center experiences have been considered. Overall, an increasing level of evidence supports the use of DCB for the treatment of long, complex, heavily calcified femoropopliteal non-occlusive and occlusive lesions, including failure after BM stent implantation due to ISR. However, more studies will be necessary to investigate the long-term effects of DCB-treatment in these real-world lesions.

The role of drug-coated balloons in in-stent restenosis.

Despite a constantly expanding spectrum of therapeutic options for lower limb artery disease, there is not yet a well-defined consensus on the specific type of endovascular treatment that is best suited. Clinical data on patients with femoropopliteal disease treated with drug-coated balloons have not been elaborated sufficiently, especially in the case of in-stent restenosis. For this review a systematic research of the medical databases (Pubmed) has been conducted. Keywords such as "drug-coated balloons" (DCB), "drug-eluting balloons," "in-stent restenosis", "de novo stenosis", "angioplasty", "superficial femoral artery," "popliteal artery," "above the knee," "below the knee," "peripheral artery disease" (PAD) have been used. Furthermore, data from reviews, original contributions regarding randomized controlled studies, observational studies, registries and single center experiences have been included. Many trials have shown superiority for DCB- over percutaneous transluminal angioplasty-treatment alone in TASC IIA and TASC IIB femoropopliteal lesions. However, the currently available DCB systems are different in terms of efficacy and long-term outcomes depending on their mechanical and pharmacological features. Moreover, angiographic characteristics of femoropopliteal lesions classified by Tosaka seem to influence subsequent outcomes of DCB treatment. Lastly, there is still lack of reliable prospective long-term data regarding DCB technology.

Myocardial Perfusion Reserve and Strain-Encoded CMR for Evaluation of Cardiac Allograft Microvasculopathy.

OBJECTIVES: This study sought to evaluate myocardial perfusion reserve index (MPRI) and diastolic strain rate, both assessed by cardiac magnetic resonance (CMR) as a noninvasive tool for the detection of microvasculopathy. BACKGROUND: Long-term survival of cardiac allograft recipients is limited primarily by cancer and cardiac allograft vasculopathy (CAV). Besides epicardial CAV, diagnosed by coronary angiography, stenotic microvasculopathy was found to be an additional independent risk factor for survival after heart transplantation. METHODS: Sixty-three consecutive heart transplant recipients who underwent CMR, coronary angiography, and myocardial biopsy were enrolled. Stenotic vasculopathy in microvessels was considered in myocardial biopsies by immunohistochemistry and CAV was graded during coronary angiography according to International Society of Heart and Lung Transplantation criteria. In addition, by CMR microvasculopathy was assessed by myocardial perfusion reserve during pharmacologic hyperemia with adenosine and strain-encoded magnetic resonance using a modified spatial modulation of magnetization tagging pulse sequence in all patients. RESULTS: Decreasing MPRI and diastolic strain rates were observed in patients with decreasing microvessel luminal radius to wall thickness ratio and decreasing capillary density (r = 0.45 and r = 0.61 for MPRI and r = 0.50 and r = 0.38 for diastolic strain rate, respectively; p < 0.005 for all). Using multivariable analysis, both MPRI and diastolic strain rate were robust predictors of stenotic microvasculopathy, independent of age, organ age, and CAV by International Society of Heart and Lung Transplantation criteria (hazard ratio: 0.07, p = 0.006 for MPRI; hazard ratio: 0.91, p = 0.002 for diastolic strain rate). Patients without stenotic microvasculopathy in the presence of no or mild CAV (n = 36) exhibited significantly higher median survival free of events, compared with patients with stenotic microvasculopathy in the presence of no or mild CAV (n = 18; p = 0.04 by log rank). CONCLUSIONS: CMR represents a valuable noninvasive diagnostic tool, which may be used for the early detection of transplant microvasculopathy before the manifestation of CAV during surveillance coronary angiographic procedures.

Impact of troponin I-autoantibodies in chronic dilated and ischemic cardiomyopathy.

The aim of this study was to investigate the prognostic value of circulating troponin I (TNI)-autoantibodies in plasma of patients with chronic heart failure. Sera of 390 heart failure patients were tested for the presence of anti-TNI antibodies by enzyme-linked immunosorbent assay (ELISA), including 249 (63.8% of total) patients with dilated cardiomyopathy (DCM) and 141 (36.2% of total) patients with ischemic cardiomyopathy (ICM). A total of 72 patients (18.5% of total) were female and 318 (81.5% of total) were male. Mean patient age was 54.6 ± 11.3 years and mean follow-up time was 3.8 ± 3.2 years. TNI-autoantibodies (titer of ≥1:40) were detected in 73 out of 390 patients (18.7% of total). In TNI-autoantibody positive patients mean left ventricular ejection fraction (LVEF) was 27.6 ± 5.8%, compared to 25.8 ± 5.9% in TNI-autoantibody negative patients, P = 0.03. The combined end-point of death (n = 118, 30.3% of total) or heart transplantation (HTX) (n = 44, 11.3% of total) was reached in 162 patients (41.5% of total). Kaplan-Meier analysis demonstrated superior survival (combined end-point of death or HTX) in patients with DCM versus ICM (P = 0.0198) and TNI-autoantibody positive patients versus TNI-autoantibody negative patients (P = 0.0348). Further subgroup analysis revealed a favorable outcome in TNI-positive patients with heart failure if the patients suffered from DCM (P = 0.0334), whereas TNI-autoantibody status in patients with ICM was not associated with survival (P = 0.8486). In subsequent multivariate Weibull-analysis, a positive TNI serostatus was associated with a significantly lower all-cause mortality in DCM patients (P = 0.0492). The presence of TNI-autoantibodies in plasma is associated with an improved survival in patients with chronic DCM, but not ICM. This might possibly indicate a prophylactic effect of TNI-autoantibodies in this subgroup of patients, encouraging further studies into possible protective effects of antibodies against certain cardiac target structures.

Effects of protein A immunoadsorption in patients with chronic dilated cardiomyopathy.

OBJECTIVES: The objective of this study was to investigate functional effects of immunoadsorption (IA) in patients with chronic nonfamilial dilated cardiomyopathy (DCM) regarding clinical and humoral markers of heart failure. BACKGROUND: IA has been shown to induce early hemodynamic improvement in patients with nonfamilial dilated cardiomyopathy (DCM). METHODS: We performed IA using protein A agarose columns on five consecutive days in 51 patients with chronic DCM, congestive heart failure of NYHA class ≥ II, left ventricular ejection fraction ≤50%, and mean time since initial diagnosis of 5.0 ± 5.8 years. RESULTS: Immediately after IA, immunoglobulin G (IgG) decreased by 89.4% and IgG3 by 66.7% (both P < 0.0001). Median NT-pro BNP was reduced from 1230.0 ng L(-1) at baseline to 829.0 ng L(-1) after 6 months (P < 0.0001). Also mean left ventricular ejection fraction (LVEF) was significantly improved (26.3% ± 9.4% to 28.7% ± 11.4% after 6 months, P = 0.016) and LVEF improved ≥5% (absolute) in 21 of 51 (41.2%) patients. After 6 months, bicycle spiroergometry showed a significant increase in exercise capacity from 82.0 ± 30.8 Watts to 93.1 ± 34.3 Watts (P = 0.008) while VO2max rose from 15.0 ± 4.1 to 16.4 ± 4.8 mL min(-1) kg(-1) (P = 0.01). CONCLUSIONS: In this study, on heart failure patients with nonfamilial DCM, IA therapy significantly improved clinical and humoral markers of heart failure severity. These promising results may be due to the selected study population, with a shorter disease duration and the higher amount of IgG 3 reduction. Future blinded prospective multicenter studies are necessary to identify those patients that benefit most.

Negative pretransplant serostatus for Toxoplasma gondii is associated with impaired survival after heart transplantation.

Chronic Toxoplasma gondii infection is known to trigger potentially adverse immunoregulatory changes, but limited data exist on long-term implications for heart transplant (HTX) recipients. We evaluated the risk of all cause mortality regarding T. gondii serostatus prior to HTX. Pre-HTX T. gondii serostatus was obtained in 344 recipients and 294 donors. Mean age was 52.1 +/- 10.2 years and mean follow-up time after HTX was 5.7 (+/-5.5, median 3.5) years. All seronegative patients received prophylaxis with pyrimethamine/sulfomethoxazole or cotrimoxazol for 6 months after transplantation. Multivariate survival analysis adjusted for diabetes mellitus, pre-HTX renal function, recipient age, type of primary immunosuppression (i.e. HTX before 2001), cytomegalovirus (CMV) high-risk status, ischemic time, and number of treated rejection episodes was performed. Overall, 190 recipients (55.2% of total) were seronegative and 154 (44.8% of total) were seropositive for T. gondii prior to HTX. One hundred and fifty-two recipients died during follow-up (44.2% of total). Negative recipient Toxoplasma serostatus was associated with a significantly higher risk of all-cause mortality (P = 0.0213). Recipient T. gondii serostatus did not influence the number of cellular or humoral rejection episodes. Analyses of specific causes of death showed a trend toward a higher number of infection-related deaths in the seronegative subgroup (P = 0.13). No statistically significant effects of T. gondii donor/recipient seropairing, or seroconversion were observed. Negative preoperative serostatus for T. gondii in HTX recipients appears to be an independent risk factor associated with increased all-cause mortality. The cause of impaired survival in Toxoplasma seronegative recipients is currently unclear; possible explanations include an alteration of immune-reactivity/-regulation or adverse effects of prophylactic medication.

Inhibition of IL-17A attenuates atherosclerotic lesion development in apoE-deficient mice.

The importance of an (auto)immune response in atherogenesis is becoming increasingly well understood. IL-17A-expressing T cells modulate immune cell trafficking, initiating inflammation and cytokine production in (auto)immune diseases. In human carotid artery plaques, we previously showed the presence of IL-17A-producing T cells and IL-23; however, IL-17A effects on atherogenesis have not been studied. Aortic root sections from 8-wk-old apolipoprotein E-deficient mice fed a standard chow diet were examined after 12 wk for lesion area, plaque composition, cellular infiltration, cytokine expression, and apoptosis. The treatment group (n = 15) received anti-IL-17A Ab and the controls (n = 10) received irrelevant Abs. Inhibition of IL-17A markedly reduced atherosclerotic lesion area (p < 0.001), maximal stenosis (p < 0.001), and vulnerability of the lesion. IL-17A mAb-treated mice showed reduced cellular infiltration, down-regulation of activation markers on endothelium and immune cells (e.g., VCAM-1), and reduced cytokine/chemokine secretion (e.g., IL6, TNFalpha, CCL5). To investigate possible mechanisms, different atherogenic cell types (e.g., macrophages, dendritic cells, HUVECs, vascular smooth muscle cells) were stimulated with IL-17A in addition to TNF-alpha, IFN-gamma, or LPS to induce cellular activation or apoptosis in vitro. Stimulation with IL-17A induced proinflammatory changes in several atherogenic cell types and apoptotic cell death in murine cells. Functional blockade of IL-17A reduces atherosclerotic lesion development and decreases plaque vulnerability, cellular infiltration, and tissue activation in apolipoprotein E-deficient mice. The present data support a pathogenic role of IL-17A in the development of atherosclerosis by way of its widespread proinflammatory and proapoptotic effects on atherogenic cells.

Heart rate reduction for 12 months with ivabradine reduces left ventricular mass in cardiac allograft recipients.

BACKGROUND: Graft denervation in heart transplant recipients causes sinus tachycardia, occasionally requiring pharmacologic heart rate reduction. Currently, no 12-month data regarding effects of the novel I(f) channel antagonist ivabradine on heart rate control, effects on left ventricular mass, tolerability, and safety are available in patients after heart transplantation (HTX). METHODS: Mean heart rate, left ventricular mass indexed (LVMI) to body surface area, tolerability, and safety of ivabradine therapy were evaluated at baseline and after 12 months in 30 HTX recipients with marked sinus tachycardia. RESULTS: In three patients (10.0% of total), ivabradine medication was discontinued. Further analysis was based on 27 patients with 12-month drug exposure. Mean patient age was 53.3+/-11.3 years, and mean time after HTX was 5.0+/-4.8 years. Mean ivabradine dose was 12.5 mg/day (+/-3.3 mg). Mean heart rate was reduced from 96.2+/-8.6 beats per minute (bpm) at baseline to 80.9+/-8.1 bpm at follow-up (P<0.0001). A statistically significant effect of heart rate reduction on LVMI was observed (104.3+/-22.7 g at baseline vs. 95.9+/-18.5 g at follow-up, P=0.04). No statistically significant changes in immunosuppressive drug dosage or blood levels were observed, except from a lower mycophenolate mofetil dose at follow-up (P=0.01). Safety laboratory values were unchanged. No phosphenes were observed. CONCLUSIONS: Heart rate reduction with ivabradine is effective and safe in heart transplant recipients. After 12 months, significant effects on LVMI were observed. Therefore, ivabradine may offer a beneficial effect on left ventricular remodelling in HTX patients.

Effects of protein A immunoadsorption in patients with advanced chronic dilated cardiomyopathy.

OBJECTIVES: The objective of this study was to investigate functional effects of immunoadsorption (IA) in severely limited study patients with chronic nonfamilial dilated cardiomyopathy (DCM), and to analyze the prevalence of Troponin I (TNI) autoantibodies. BACKGROUND: Immunoadsorption (IA) has been shown to induce early hemodynamic improvement in patients with nonfamilial DCM. METHODS: We performed IA using Immunosorba columns on five consecutive days in 27 patients with chronic DCM, congestive heart failure of NYHA class >or=II, left ventricular ejection fraction below 40%, and mean time since initial diagnosis of 7.2 +/- 6.8 years. RESULTS: Immediately after IA, IgG decreased by 87.7% and IgG3 by 58.5%. Median NT-pro BNP was reduced from 1740.0 ng/L at baseline to 1504.0 ng/L after 6 months (P = 0.004). Mean left ventricular ejection fraction (LVEF) was not significantly improved overall (24.1 +/- 7.8% to 25.4 +/- 10.4% after 6 months, P = 0.38), but LVEF improved >or=5% (absolute) in 9 of 27 (33%) patients. Bicycle spiroergometry showed a significant increase in exercise capacity from 73.7 +/- 29.4 Watts to 88.8 +/- 31.1 Watts (P = 0.003) after 6 months while VO2max rose from 13.7 +/- 3.8 to 14.9 +/- 3.0 mL/min kg after 6 months (P = 0.09). Subgroup analysis revealed a higher NT-pro BNP reduction in patients with shorter disease duration (P = 0.03) and without TNI autoantibodies at baseline (P = 0.05). All 9 patients with an absolute increase of LVEF of >or=5.0% were diabetic (P = 0.0001). CONCLUSIONS: In this study, on severely limited heart failure patients with nonfamilial DCM, IA therapy moderately improved markers of heart failure severity in a limited subgroup of patients. This may be due to the selected study population with end-stage heart failure patients and the lower reduction of IgG3 compared to previous studies. Future blinded multicenter studies are necessary to identify those patients that benefit most.

Return to work after heart transplantation: discrepancy with subjective work ability.

BACKGROUND: This study evaluates the objective rate of return to work after heart transplantation (HTX) in comparison with the patients' subjective rating of their work ability and identifies predictors for return to work in a German heart transplant center. METHODS: A questionnaire covering demographics, clinical data, and professional aspects was sent to 200 heart transplant recipients at least 12 months after HTX. Participation was strictly anonymous enabling reliable results concerning subjective work ability. RESULTS: Response rate was 150 of 200 (75%). During the time after HTX, 45 of 150 (30.0%) patients had ever been in a job. Thirty-five of 95 (36.8%) patients of formal working age (<65 years) were employed after 12.6+/-1.9 months: 18 of 95 (18.9%) in full-time work, 9 of 95 (9.5%) in part-time work, and 6 of 95 (6.3%) in casual employment. Two of 95 (2.1%) patients worked as handicapped employees; only 1 of 95 (1.1%) patients was currently seeking work. Patients obtained financial benefits from their illness (n=54; 36%) or age-related annuity (n=8; 5.3%). Forty-two of 95 (44.2%) patients did not feel capable of working, three patients did not answer, and 50 of 95 patients (52.6%) felt fit for employment. Employment after HTX depended on age, duration of unemployment, diabetes mellitus, and financial need for paid employment. Financially independent patients (n=66) more often felt unable to work by subjective judgement (n=34/67; 50.7%) than patients who depended on paid employment (8/28; 28.6%; P<0.05). CONCLUSIONS: The rate of employment after HTX in Germany is significantly lower than the subjective perception of the individual ability to work; underscoring the importance of sociodemographic and psychologic aspects during rehabilitation of HTX recipients.

Beneficial effect of omega-3 fatty acids on sirolimus- or everolimus-induced hypertriglyceridemia in heart transplant recipients.

BACKGROUND: Hyperlipidemia is an important complication after organ transplantation and may contribute to the development of posttransplant-accelerated coronary artery disease. Immunosuppressive therapy, especially mammalian target of rapamycin inhibitors, induces a considerable increase in cholesterol and triglyceride plasma levels. Omega-3 fatty acids (FAs) exert cardioprotective effects supporting a therapeutic role in cardiovascular conditions. METHODS: An observational study of omega-3 FAs 4 g/day was performed in 15 heart transplant recipients with hypertriglyceridemia. Six patients received rapamycin, and nine received everolimus. Apart from one patient the immunosuppressive therapy was combined with mycophenolate mofetil, only one patient received steroids; two patients presented with diabetes. RESULTS: Mean triglyceride levels before heart transplantation (HTx) were 137+/-54 mg/dL. After HTx, before sirolimus or everolimus treatment triglyceride level had increased to 188+/-67 mg/dL (P<0.05). Treatment with sirolimus or everolimus induced an increase in triglycerides to 354+/-107 mg/dL (P<0.001). Subsequent treatment with omega-3 FAs for 4 months resulted in a marked decrease in triglycerides to 226+/-74 mg/dL (P<0.001). All patients (100%) showed a reduction in triglyceride by more than 20% (responders). In 10 of 15 patients available 12-month data confirmed the long-term efficacy of omega-3 FAs treatment. There were no adverse events or any discontinuations; no changes in immunosuppression were required. CONCLUSIONS: Treatment with mammalian target of rapamycin inhibitors after HTx induces marked increase in serum levels of triglycerides. Omega-3 FAs significantly lower triglyceride levels and seem to be effective, safe, and well-tolerated in sirolimus- or everolimus-treated heart transplant recipients.

Epstein-Barr virus load in whole blood is associated with immunosuppression, but not with post-transplant lymphoproliferative disease in stable adult heart transplant patients.

Development of Epstein-Barr virus (EBV)-associated post-transplant lymphoproliferative disease (PTLD) is a serious complication following heart transplantation (HTX). This study investigates EBV DNA load in adult heart transplant recipients, its association with immunosuppression, and its potential as a marker for development of PTLD. EBV DNA load was measured prospectively by quantitative real-time polymerase chain reaction (PCR) in 172 stable HTX patients. Sixty-seven patients (39.0% of total) had a positive EBV PCR at initial examination [median 4.9 (range 1.1-16.9) years post-HTX]. In follow-up testing of 67 positive patients 6 months later, 36 patients continued to have a positive EBV PCR. Overall incidence of EBV DNA was significantly associated with calcineurin inihibitors, azathioprine medication, and with the absence of mycophenolate mofetil (MMF) treatment. In patients with positive EBV DNA levels at initial examination and negative levels at retesting, cyclosporine A levels were found to be significantly higher at initial examination (148.4 +/- 70.2 vs. 119.6 +/- 53.5 ng/ml, P < 0.05). Three patients (1.7%, 3/172) were diagnosed with PTLD during the course of the study (mean follow up 4.0 years). EBV DNA viral load determination does not appear to be useful for risk prediction or early diagnosis of PTLD in adults after HTX, but an association of EBV DNA load with qualitative and quantitative immunosuppression is demonstrated.

Heart rate reduction after heart transplantation with beta-blocker versus the selective If channel antagonist ivabradine.

BACKGROUND: Graft denervation in heart transplant recipients causes sinus tachycardia, occasionally requiring pharmacologic heart rate reduction. The If channel antagonist ivabradine has not been compared to beta-blocker after heart transplantation. Heart rate control, tolerability, short-term safety, and effects on exercise capacity were studied consecutively with an established heart rate-reducing drug (metoprolol succinate) compared to a novel agent (ivabradine) in heart transplant recipients. METHODS: In 25 heart transplant recipients, heart rate, exercise capacity, and patient preference were assessed under no medication (baseline) and after consecutive 8-week treatment periods under metoprolol and ivabradine. RESULTS: Drug discontinuation following side effects occurred in 5 patients (metoprolol: 4, ivabradine: 1); per-protocol analysis was performed on 20 patients completing both consecutive treatment periods. Mean heart rate was reduced from baseline (96.5+/-7.0 bpm) to 84.4+/-8.8 bpm on beta-blocker (P=0.0004 vs. baseline) and to 76.2+/-8.9 bpm with ivabradine (P=0.0001 vs. baseline and P=0.003 vs. beta-blocker). Exercise capacity by spiroergometry was not altered by either drug. Relevant pharmacokinetic interaction with immunosuppressants was not seen under ivabradine; safety laboratory values were unchanged. Mild adverse effects were noted in 45% of patients during beta-blocker and 20% during ivabradine treatment. Questionnaire analysis demonstrated patient preference for heart rate reduction with ivabradine. CONCLUSIONS: Heart rate reduction with ivabradine is effective and potentially better tolerated than beta-blocker therapy in heart transplant recipients. Although the prognostic role of heart rate after HTX is unknown, ivabradine may offer relevant symptomatic benefit, especially in cases of beta-blocker intolerance.

Platelet-associated LIGHT (TNFSF14) mediates adhesion of platelets to human vascular endothelium.

LIGHT (TNFSF 14) belongs to the tumor necrosis factor super-family and is expressed by different types of immune cells. Recently, LIGHT was found to be associated with platelets and released upon activation. Activation of endothelial cells by recombinant LIGHT results in pro-inflammatory and pro-thrombotic changes, qualitatively comparable to effects of CD40 ligand. Given the important role of platelet-associated CD40 ligand in vascular inflammatory responses we investigated the role of LIGHT for activation of endothelium and adhesion of platelets to endothelial cells. Expression of LIGHT was detected on thrombocytes upon exposure to ADP or TRAP-1. The expression of the LIGHT receptors TR2 and LTbetaR on native human endothelial cells was confirmed by FACS analysis. LIGHT mediated adhesion of platelets to endothelium significantly, occurring both under static and dynamic flow conditions. This interaction was inhibited by a monoclonal antibody to LIGHT but not a control IgG. Moreover, in-vitro stimulation of endothelial cells with recombinant soluble human LIGHT (rhLIGHT) resulted in significantly increased transcriptional and translational upregulation of inflammatory markers ICAM-1, tissue factor (TF) and IL-8. This activation of endothelial cells by LIGHT was mediated by NFkappaB activation and qualitatively comparable to that induced by membrane-bound CD40-ligand on transfected cells. Furthermore, plasma levels of patients with myocardial infarction, in those with ST-elevation myocardial infarction (STEMI), showed increased plasma levels of LIGHT compared with healthy controls. In conclusion, platelet-associated LIGHT is involved in adhesion of platelets to endothelium while soluble LIGHT induces a pro-inflammatory state in vascular endothelial cells. LIGHT may thus be implicated in the pathogenesis of atherosclerosis and acute coronary syndrome, as evidenced by serum levels.

IL-10 inhibits endothelium-dependent T cell costimulation by up-regulation of ILT3/4 in human vascular endothelial cells.

Effects of IL-10 on endothelium-dependent T cell activation have not been investigated in detail. We confirm expression of the IL-10 receptor and effective signaling via STAT-3 in human umbilical vein endothelial cells (HUVEC). In CD4 T cell cocultures with HUVEC, pretreatment of endothelial cells with IL-10 resulted in significant dose-dependent inhibition of CD4 T cell proliferation, which also occurred when IL-10 was removed after pretreatment before starting cocultures. Th1/Th2 polarization of proliferated T cells, endothelial nitric oxide (NO), or IL-12 production were unchanged. However, IL-10 stimulation resulted in up-regulation of SOCS-3, a negative regulator of cytokine secretion, and induction of the inhibitory surface molecules immunoglobulin-like transcript 3 and 4 (ILT3/ILT4) in EC, potentially involving glucocorticoid-induced leucine zipper (GILZ). Addition of blocking antibodies against ILT3/ILT4 to EC/T cell cocultures resulted in nearly complete reestablishment of T cell proliferation. In contrast, addition of soluble ILT3 or overexpression of ILT3 in cocultures significantly reduced T cell proliferation. No induction of foxp3+ regulatory T cells was seen. In conclusion, the T cell costimulatory potential of human EC is markedly suppressed by IL-10 due to up-regulation of ILT3/ILT4, obviously not involving generation of Treg. This identifies a novel action of IL-10 in EC and a potential therapeutical target for local immunomodulation.