Search

Summary Background The number of dialysis patients is steadily increasing. Associated comorbidities include impaired bone and mineral metabolism, termed chronic kidney disease-mineral and bone disorder (CKD-MBD), leading to a high fracture risk, increased morbidity and mortality and impaired quality of life. While the bone density is assessed with dual-energy X‑ray absorptiometry (DXA), the trabecular bone score (TBS) captures the image texture as a potential index of skeletal microarchitecture. The aim of this study was to evaluate the clinical relevance of DXA and TBS in dialysis patients with and without prevalent fractures. Methods Bone disorders were evaluated in 82 dialysis patients (37% female) at the University Hospital of Graz, Austria, by DXA including the assessment of the TBS based on a patient interview and the local routine patient database software. The patient cohort was stratified by having sustained a fragility fracture in the past or not. Descriptive statistics, t‑tests for continuous variables and χ2-tests for nominal variables including results of DXA and TBS were performed to compare these groups considering the dialysis modality and duration as well as the number of kidney transplantations. Results Of the 82 patients, 32 (39%) had a positive history of fractures. There was a significant association between dialysis duration and fracture prevalence (p p p Conclusion The use of DXA has a limited role in fracture prediction in dialysis patients; however, the TBS seems to add information as an additional tool for fracture risk estimation in this patient population.

Hemodialysis patients (HD) are expected to have excess mortality in coronavirus disease 2019 (COVID-19). This was challenged by a recent study reporting HD patients to have comparable mortality and less ICU admissions when hospitalized with COVID-19. An altered immune system due to chronic inflammation might protect HD-patients from severe COVID-19. Therefore, we aimed to describe the peripheral blood immune phenotype in HD-patients and respective controls with COVID-19.MethodsSixty-four patients (31 HD, 33 non-HD) with PCR-confirmed COVID-19 and 16 control patients (10 HD, 6 non-HD) were prospectively included. According to symptoms, COVID-19 patients were categorized as asymptomatic/mild, moderate or severe COVID-19 phenotypes. Cytokine profiling and immune phenotyping was performed.ResultsTh1 and Th17 plasma cytokine levels were highly increased in HD patients without COVID-19 and were not significantly regulated during COVID-19. In non-HD COVID-19 patients these cytokines increased significantly with disease severity. While all patients with moderate or severe COVID-19 showed hallmarks of COVID-19 such as decreased CD3+, CD4+ and CD8+ and CD4+CD25hiFoxP3+ regulatory T cells, significantly increased CD38+CD8+ effector memory and CD38+CD8+ TEMRA T cells were detected in moderate/severe COVID-19 HD patients, which was not observed in non-HD patients with moderate or severe COVID-19. Furthermore, CD161+CD8+ T cells decreased significantly in non-HD COVID-19 patients dependent on disease severity, but not in HD patients. Dynamics of B cells and subtypes were comparable in HD and non-HD COVID-19 patients.ConclusionsHD patients might be protected from severe COVID-19 due to their chronic inflammatory state with increased CD38+CD8+ effector memory and TEMRA T cells as well as CD161+CD8+ T cells.

BACKGROUND: Cardiovascular morbidity and mortality are higher among patients with type 2 diabetes, particularly those with concomitant cardiovascular diseases, than in most other populations. We assessed the effects of lixisenatide, a glucagon-like peptide 1-receptor agonist, on cardiovascular outcomes in patients with type 2 diabetes who had had a recent acute coronary event.METHODS: We randomly assigned patients with type 2 diabetes who had had a myocardial infarction or who had been hospitalized for unstable angina within the previous 180 days to receive lixisenatide or placebo in addition to locally determined standards of care. The trial was designed with adequate statistical power to assess whether lixisenatide was noninferior as well as superior to placebo, as defined by an upper boundary of the 95% confidence interval for the hazard ratio of less than 1.3 and 1.0, respectively, for the primary composite end point of cardiovascular death, myocardial infarction, stroke, or hospitalization for unstable angina.RESULTS: The 6068 patients who underwent randomization were followed for a median of 25 months. A primary end-point event occurred in 406 patients (13.4%) in the lixisenatide group and in 399 (13.2%) in the placebo group (hazard ratio, 1.02; 95% confidence interval [CI], 0.89 to 1.17), which showed the noninferiority of lixisenatide to placebo (PCONCLUSIONS: In patients with type 2 diabetes and a recent acute coronary syndrome, the addition of lixisenatide to usual care did not significantly alter the rate of major cardiovascular events or other serious adverse events. (Funded by Sanofi; ELIXA ClinicalTrials.gov number, NCT01147250.).

The cardiovascular effect of liraglutide, a glucagon-like peptide 1 analogue, when added to standard care in patients with type 2 diabetes, remains unknown. METHODS In this double-blind trial, we randomly assigned patients with type 2 diabetes and high cardiovascular risk to receive liraglutide or placebo. The primary composite outcome in the time-to-event analysis was the first occurrence of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke. The primary hypothesis was that liraglutide would be noninferior to placebo with regard to the primary outcome, with a margin of 1.30 for the upper boundary of the 95% confidence interval of the hazard ratio. No adjustments for multiplicity were performed for the prespecified exploratory outcomes. RESULTS A total of 9340 patients underwent randomization. The median follow-up was 3.8 years. The primary outcome occurred in significantly fewer patients in the liraglutide group (608 of 4668 patients [13.0%]) than in the placebo group (694 of 4672 [14.9%]) (hazard ratio, 0.87; 95% confidence interval [CI], 0.78 to 0.97; P, Novo Nordisk; National Institutes of Health; LEADER ClinicalTrials.gov

This article reports on the first double-blind randomized clinical study with an antiidiotype antibody vaccine in patients with metastatic colorectal carcinoma. The study was performed to determine immunological parameters, efficacy, and tolerability of the vaccine. Forty-two patients with metastatic colorectal cancer were randomly assigned to multiple immunizations with goat IgG antiidiotype vaccine SCV 106 (n = 21) or unspecific goat IgG as controls (n = 21). The antiidiotype vaccine mimicked the 17-1A glycoprotein antigen associated with colorectal cancer. Of the 42 patients entered, 39 were evaluable for efficacy (SCV 106, n = 18; controls, n = 21). Twenty-nine patients raised antibodies to the vaccines (immunological responders, SCV 106, n = 12; controls, n = 17). Only in the SCV 106 group was a significant increase (p = 0.002) of titers with specificity of antitumor antibody 17-1A found. According to the International Union Against Cancer (UICC) criteria no tumor response was observed. However, in the SCV 106 group the relative increase of carcinoembryonic antigen (CEA) levels between entry and observed disease progression was lower (p = 0.03) and disease progression was determined less frequently by development of new metastases (p = 0.001). On an intention-to-treat basis, the survival time difference between the two groups was not significant. Comparison of immunological responders in both groups revealed a significant survival advantage of the SCV 106-treated patients compared with controls (mean 67 versus 39 weeks; p = 0.01). Immunizations were well tolerated. Vaccination of immunologically responding metastatic colorectal carcinoma patients with SCV 106 leads to slowed disease progression and tumor dissemination and significantly prolongs survival time.

Troponin T is used as a marker for myocardial cell damage (e.g., in aiding diagnosis and follow-up of myocardial infarction). Elevated troponin T levels are also observed after heart transplantation, although until now no explanation could be found for this phenomenon.Serum samples of 15 patients who underwent orthotopic heart transplantation were tested for troponin T with a one-step enzyme immunoassay. The highest concentrations of troponin T were seen between day 3 and 14 after transplantation (3.05 +/- 1.30 micrograms/L) and remained elevated up to 3 months. A correlation (r = 0.61, p0.02) was found between pretransplantation systolic pulmonary artery pressure and the cumulative troponin T release after transplantation. No association was found with rejection, and no correlation was found with ischemic time of the donor heart.These findings support the hypothesis that the acute exposure of the donor heart to the preexisting elevated right ventricular afterload in the recipient represents a strong mechanical stress for the transplanted heart. Measurement of troponin T may therefore be helpful in the posttransplantation monitoring and management of ventricular function after orthotopic heart transplantation.

The clinical spectrum of acute pancreatitis ranges from mild, self-limiting disease of fulminant illness that may rapidly lead to multiple organ failure and death. To identify factors associated with a subsequent severe course and/or high mortality we investigated retrospectively 91 patients admitted to the medical intensive care unit (ICU) with acute pancreatitis during a 2 year period. 67% of the attacks were mild (or = 1 complication). The overall mortality rate was 9%, whereby 3% of patients with alcoholic and 13% with biliary pancreatitis died. 75% of the patients in the group with a fatal outcome were aged over sixty and 30% in the group with a mild course (p0.05). Females with pancreatitis of biliary origin had a mild course in 57% and a severe (or = 2 complications) or fatal outcome in 43%. In males with alcohol abuse we observed a mild form of pancreatitis in 79% and a severe or fatal course in 21%. The delay between onset of abdominal pain and commencement of treatment in hospital was greater than 12 hours in 70% of all patients studied and there was no association with severity and development of subsequent complications. The median of the acute physiology and chronic health evaluation scoring system (APACHE-III) on the day of admission was 19 in patients with mild disease, which was significantly lower than in patients with severe (40) or fatal acute pancreatitis (53) (p0.0001). Serial APACHE-III measurements over 5 days after admission provided further differentiation between mild and severe or fatal cases (p0.0001), but no significant difference was observed between survivors with severe course and fatal outcome. In addition, RANSON scores were calculated for comparison with APACHE-III at admission and after 48 hours: concerning the recognition between mild and severe/fatal pancreatitis both scoring systems exhibited similar significant differences on day 1 and day 2. The RANSON scoring system provided further a significant differentiation between survivors with a severe course of pancreatitis when compared to deaths on day 2, whereas the APACHE-III scoring system did not. Advanced age, female sex, biliary obstruction and elevated RANSON and APACHE-III scores are risk factors for an increased rate of life-threatening complications in acute pancreatitis. The daily assessment of such scoring systems may allow the recognition of such patients and may be helpful in the routine clinical management and monitoring of acute pancreatitis.

Arterial hypertension is an important risk factor for excessive cardiovascular morbidity and mortality due to its high prevalence of about 20% in the adult population. Causal readings, which have been obtained for diagnosis and control of treatment in hypertension are of limited value. They are not reproducable due to physiologic variability of blood pressure, which causes a rise of blood pressure, if a straining situation (e.g. in doctor's office) occurs (white-coat-hypertension). Furthermore, no correlation between causal readings and signs of endorgan-damage (EOD) such as left ventricular hypertrophy (LVH) can be observed. Especially the development of LVH comprises an independent risk factor and worsens prognosis. Results of ambulatory monitoring and self-measurement of blood pressure are reproducable and show an excellent correlation to EOD. Both methods are able to exclude white-coat-hypertension. Furthermore, ambulatory blood pressure monitoring allows to obtain blood pressure values during sleep, which may give further information concerning secondary hypertension, EOD and prognosis. Self measurement of blood pressure reinforces compliance of the patient and gives the possibility of self-titration and long-term control of antihypertensive drug treatment. The non-consensus concerning normal values is one limitation of both methods, but the cut-off level of office blood pressure recordings appears arbitrary, too. For optimal concomittance of hypertensives both methods have to reach more importance for diagnosis, evaluation of prognosis as well as treatment control.

To improve diabetes care according to the St. Vincent Declaration an interdisciplinary working group on erectile dysfunction in patients with diabetes was installed in the Departments of Internal Medicine, Urology and Psychiatry at the University of Graz. The screening and basic diagnostic procedures are performed in the diabetes clinic in the Department for Internal Medicine. To inform the patients about the options of treatment of diabetic erectile dysfunction and to determine prevalence data an anonymous questionnaire with a pre-stamped envelope was sent to 133 male patients with diabetes mellitus type I (IDDM). 59 (44%) of the questionnaires were returned and could be analyzed. Mean age and diabetes duration were representative for the male diabetes population. The prevalence of erectile dysfunction in this group was 49%. 7% of the patients were completely impotent. None of the patients reported the use of erection aids as a vacuum device or intracavernosal injection of smooth muscle-relaxant drugs. The prevalence of erectile dysfunction is high among patients with diabetes mellitus type I. Modern management offers satisfactory success in most cases, therefore screening for erectile dysfunction and adequate therapy should be offered to all patients.

In 28 type II diabetics with secondary failure of sulfonylurea treatment, the efficacy and safety of combined therapy with insulin and glibenclamide were investigated. Patients were randomized in two groups and treated for 16 weeks either with insulin Novo Protaphan HM Penfill (100 IU/ml "bed time") and 10 mg of glibenclamide in the morning (group A), or with insulin Novo Actraphan HM Penfill 100 IU/ml in the morning combined with two 5 mg doses of glibenclamide at lunchtime and in the evening (group B). Subsequently a dropout trial of sulfonylurea was performed in half of the patients. Mean blood glucose levels were lowered in the whole group of patients from 13.5 +/- 1.8 mmol/l to 8.8 +/- 2.3 mmol/l after 8 weeks and 8.7 +/- 1.8 mmol/l after 16 weeks, and the HbAlc from 10.1 +/- 1.2% to 8.4 +/- 1.0% and 7.8 +/- 1.0% respectively. After a glibenclamide dropout period of one or two weeks in 14 of the patients, the mean blood glucose level rose significantly by 2.8 +/- 2.6 mmol/l. Only 2 patients did not show this increase. The mean insulin consumption was 13 +/- 3 IU after 8 weeks and 14 +/- 5 IU after 16 weeks respectively, and the incidence of hypoglycemia one in 12 weeks of treatment. The combination of glibenclamide and insulin (administered with the Novo Pen injector) is a safe and effective form of therapy in secondary failure of sulfonylurea, and is well accepted due to the mild start into insulin therapy.