Treatment of hyperprolactinaemia reduces total cholesterol and LDL in patients with prolactinomas.

Previous studies suggest that hyperprolactinaemia might have adverse effects on lipid and glucose metabolism. We therefore aimed to evaluate whether dopamine agonist treatment with cabergoline has significant effects on blood lipids, fasting glucose and HbA1c levels in patients with micro- or macroprolactinoma. In this retrospective observational study the main outcome measures are changes in parameters of glucose and lipid metabolism compared at hyperprolactinaemia and after achievement of normoprolactinaemia by cabergoline treatment. We enrolled 53 study participants (22 females; median [interquartile range] age: 40.0 [27.5 to 50.0] years), 22 (41.5 %) with micro-, and 31 (58.5 %) with macroprolactinomas. After a median follow-up of 9 months, prolactin levels decreased from 220.6 (80.7-913.4) to 11.2 (3.5-18.7) ng/mL (p < 0.001). There was a significant decrease in median levels of low-density lipoprotein (LDL) from 121.6 (±39.4) to 110.6 mg/dl (±37.6, p = 0.005) and total cholesterol from 191 (168.5-241) to 181 mg/dl (162-217, p < 0.001), but no change in high-density lipoprotein (HDL), triglycerides, fasting glucose and HbA1c. We observed a significant increase in testosterone in men and in oestradiol in women. In linear regression analyses using the change in total cholesterol or LDL as dependent, and the change in prolactin, oestradiol, and testosterone as independent variables, no significant predictor of the change in total cholesterol or LDL was identified. In patients with prolactinomas, normalisation of elevated prolactin levels by cabergoline treatment was accompanied by significant reductions in LDL and total cholesterol. Further studies are warranted to confirm our findings and to evaluate the clinical implications of lipid levels in the monitoring and treatment of patients with prolactinomas.

Detection of central venous catheter-related bloodstream infections in haematooncological patients.

BACKGROUND: Catheter-related bloodstream infections (CRBSIs) are currently detected in patients with clinically suspicion. The aim of our study was to evaluate whether CRBSIs could be anticipated and detected in a subclinical stage by peptide nucleic acid fluorescence in situ hybridization (PNA FISH) using universal hybridization probes or acridine orange leucocyte cytospin (AOLC) tests in haematooncological patients with central venous catheters (CVCs) in situ. MATERIALS AND METHODS: Peptide nucleic acid fluorescence in situ hybridization and AOLC tests using blood samples from one CVC lumen/port chamber in haematooncological patients were continuously performed. These results were compared to those obtained from routinely performed CRBSI diagnostic tests. RESULTS: One hundred and eighty-two patients with 342 catheter periods were investigated. Seventeen CRBSI cases were detected in 6466 CVC days by routine measures resulting in a CRBSI rate of 2.6/1000 catheter days. Two of 17 showed positive PNA FISH tests, and five positive AOLC test results before the diagnosis were established with routine measures. The screening revealed further seven patients with positive universal PNA FISH tests and 10 positive AOLC tests without symptoms indicative for infection and were therefore considered not to have CRBSI. CONCLUSIONS: Sampling of only one CVC lumen/port chamber screening for CRBSI in haematooncological patients seems not to be a useful tool for anticipative diagnosis of CRBSI. Reasons for false-negative results might include origin of CRBSIs from the other CVC lumina not sampled for screening, and false-positive results might origin from catheter colonization without subsequent spread of micro-organisms into the peripheral bloodstream.

Azacitidine in 302 patients with WHO-defined acute myeloid leukemia: results from the Austrian Azacitidine Registry of the AGMT-Study Group.

Data on efficacy and safety of azacitidine in acute myeloid leukemia (AML) with >30 % bone marrow (BM) blasts are limited, and the drug can only be used off-label in these patients. We previously reported on the efficacy and safety of azacitidine in 155 AML patients treated within the Austrian Azacitidine Registry (clinicaltrials.gov identifier NCT01595295). We herein update this report with a population almost twice as large (n = 302). This cohort included 172 patients with >30 % BM blasts; 93 % would have been excluded from the pivotal AZA-001 trial (which led to European Medicines Agency (EMA) approval of azacitidine for high-risk myelodysplastic syndromes (MDS) and AML with 20-30 % BM blasts). Despite this much more unfavorable profile, results are encouraging: overall response rate was 48 % in the total cohort and 72 % in patients evaluable according to MDS-IWG-2006 response criteria, respectively. Median OS was 9.6 (95 % CI 8.53-10.7) months. A clinically relevant OS benefit was observed with any form of disease stabilization (marrow stable disease (8.1 months), hematologic improvement (HI) (9.7 months), or the combination thereof (18.9 months)), as compared to patients without response and/or without disease stabilization (3.2 months). Age, white blood cell count, and BM blast count at start of therapy did not influence OS. The baseline factors LDH >225 U/l, ECOG ≥2, comorbidities ≥3, monosomal karyotype, and prior disease-modifying drugs, as well as the response-related factors hematologic improvement and further deepening of response after first response, were significant independent predictors of OS in multivariate analysis. Azacitidine seems effective in WHO-AML, including patients with >30 % BM blasts (currently off-label use). Although currently not regarded as standard form of response assessment in AML, disease stabilization and/or HI should be considered sufficient response to continue treatment with azacitidine.

The detection of calcium pyrophosphate crystals in the synovial fluid of patients with rheumatoid arthritis using the cytospin technique: prevalence and clinical correlation.

There are only a few studies dealing with the detection and clinical impact of calcium pyrophosphate (CPPD) crystals in patients with rheumatoid arthritis (RA) published to date. In particular, data determined by the cytospin technique, which is an effective tool to enhance the crystal detection rate, are lacking. The objectives of this study were to determine the prevalence of CPPD crystals in the synovial fluid (SF) of patients with RA and to investigate whether the detection of CPPD crystals is correlated with demographic, clinical and serological features. We examined 113 consecutive SF samples of patients with RA, obtained from therapeutic arthrocentesis of knee joints. After cytocentrifugation, the sediments were examined by polarized microscopy for the occurrence of CPPD crystals. Demographic, clinical and serological data, acquired from the medical records, were compared between crystal-positive and crystal-negative subjects. CPPD crystals were observed in 20 of the 113 cases, representing 17.7%. CPPD-positive and CPPD-negative subjects did not differ significantly in sex, duration of disease, Steinbrocker radiologic stage, disease activity score 28, as well as serum rheumatoid factor and anti-CCP positivity. Patients positively tested for CPPD crystals had a significantly higher age than CPPD-negative patients (p < 0.0001). An age-independent association of long-time treatment with diuretics and CPPD crystal formation was not found. In conclusion, demographic, clinical and serological characteristics of patients with RA were not associated with the occurrence of CPPD crystals. Age was the only significant influencing factor on CPPD crystal formation in patients with RA.

Impact of structured personal on-site patient education on low posaconazole plasma concentrations in patients with haematological malignancies.

Low posaconazole plasma concentrations (PPCs) are associated with breakthrough invasive mould infections among patients with haematological malignancies. This study evaluated the influence of structured personal on-site patient education on low PPCs. The study was conducted from July 2012 to May 2013 at the Division of Hematology, Medical University Hospital of Graz (Graz, Austria). PPCs were measured in all patients with haematological malignancies receiving the drug prophylactically. Concentrations above the target of 0.5 mg/L were defined as satisfactory and those below this concentration as low. In patients with low PPCs, structured personal on-site education regarding the intake of posaconazole (e.g. intake with fatty/acid food, prevention of nausea and vomiting) was performed. In total, 258 steady-state PPCs were measured in 65 patients [median PPC 0.59 mg/L, interquartile range 0.25-0.92 mg/L; 141/258 (54.7%) satisfactory]. Diarrhoea was the strongest predictor of low PPCs in the multivariate analysis. Initial steady-state PPCs were sufficient in 29 patients and low in 36 patients. Of the 36 patients with low initial steady-state PPCs, 8 were either discharged or antifungal therapy was modified before a follow-up PPC was obtained; in the remaining 28 patients, personal on-site education was performed. In 12/28 patients (43%) the personal on-site education led to sufficient levels, whilst in 16 (57%) PPCs stayed below the target, although increasing from <0.2 mg/L to >0.3 mg/L in 6 of these patients. In conclusion, personal education appears to be a promising tool to increase low PPCs.

Azacitidine in CMML: matched-pair analyses of daily-life patients reveal modest effects on clinical course and survival.

Recent data suggest that azacitidine may be beneficial in CMML. We report on 48 CMML-patients treated with azacitidine. Overall response rates were high (70% according to IWG-criteria, including 22% complete responses). Monocyte count and cytogenetics adversely affected survival, whereas age, WHO-type, FAB-type, and spleen size did not. Matched-pair analyses revealed a trend for higher two-year-survival for azacitidine as compared to best supportive care (62% vs. 41%, p=0.067) and longer OS for azacitidine first-line vs. hydroxyurea first-line (p=0.072, median OS 27.7 vs. 6.2 months). This report reinforces existing evidence that azacitidine is safe and efficacious in both myelodysplastic and myeloproliferative CMML.