Recruiting refugees and migrants as potential hematopoietic stem cell donors to serve patients of comparable ethnicities with rare human leucocyte antigen patterns - The BluStar.NRW project in North Western Germany.

Currently, approximately 19 million people with a migration background live in Germany. The majority of those descend from regions where the population has a genetically different distribution of HLA antigens when compared to the HLA frequencies usually found in North Western Europe. In case of severe haematological disorders of these individuals, allogeneic stem cell transplantation may be the treatment of choice. However, finding appropriate histocompatible hematopoietic stem cell donors continues to be a major challenge. If no matching sibling donors are available, there are only few suitable donors with a similar genetic background available in international blood stem cell donor registries. The "BluStar.NRW" project aimed to recruit new blood and hematopoietic stem cell donors with a migration background and to noticeably increase the number of suitable donors for patients within this group. Since December 2017, a total number of 9100 blood and stem cell donors with a migration background were recruited and typed for this project. HLA typing for HLA-A, -B, -C, -DRB1, -DQB1, and -DPB1 was performed by Next Generation Sequencing. We assessed the proportion of rare alleles according to HLA frequency tables, as defined by a frequency of <1:1000. The rare HLA allele frequencies according to HLA frequency tables of the BluStar.NRW cohort were compared with a matched control donor cohort: Rare HLA-A, -B, -C, -DRB1 and -DQB1 alleles occurred three times more frequent than in the control group, but rare HLA-DPB1 alleles occurred more frequently in the control cohort. This difference was highly significant for all HLA alleles (p < 0.0001 for HLA-A, -B, -C, -DRB1, -DPB1; p = 0.0002 for HLA-DQB1). In addition, the distribution of rare alleles differed between the two groups. To date, 29 work-ups were initiated, 12 PBSC, one BM and three DLI were collected so far out of the BluStar.NRW cohort. The apheresis probability is twofold higher (0.18% vs. 0.07%) compared to the control group which clearly shows a serious medical need. However, 13 work-ups were cancelled in the BluStar.NRW donor cohort which represents an almost twice as higher cancellation rate (45% vs. 25%). This single registry analysis with a large sample cohort clearly indicates that hematopoietic stem cell donors with a migration background represent an adequate donor pool to serve patients of comparable ethnicity.

Evaluation of Posterior Fossa Biometric Measurements on Fetal MRI in the Evaluation of Dandy-Walker Continuum.

BACKGROUND AND PURPOSE: Dandy-Walker malformation, vermian hypoplasia, and Blake pouch remnant represent a continuum of anomalies and are common reasons for referral for fetal MR imaging. This study aimed to determine biometric measurements that quantitatively delineate these 3 posterior fossa phenotypes. MATERIALS AND METHODS: Our single-center institutional review board approved a retrospective analysis of all fetal MRIs for posterior fossa malformations, including Dandy-Walker malformation, vermian hypoplasia, and Blake pouch remnant. Measurements included the anterior-to-posterior pons, craniocaudal and anterior-to-posterior vermis, lateral ventricle size, and tegmentovermian and posterior fossa angles. Measurements were compared with normal biometry and also between each subgroup. RESULTS: Thirty-three fetuses met the criteria and were included in the study. Seven were designated as having Dandy-Walker malformation; 16, vermian hypoplasia; and 10, Blake pouch remnant. No significant group interactions with adjusted mean gestational age for tegmentovermian and posterior fossa angles were observed. The tegmentovermian angle was significantly higher in Dandy-Walker malformation (109.5° [SD, 20.2°]) compared with vermian hypoplasia (52.13° [SD, 18.8°]) and Blake pouch remnant (32.1° [SD, 17.9°]), regardless of gestational age. Lateral ventricle sizes were significantly higher in Dandy-Walker malformation at a mean of ≥23.1 weeks' gestational age compared with vermian hypoplasia and Blake pouch remnant. The anterior-to-posterior and craniocaudal vermes were significantly smaller in Dandy-Walker malformation compared with vermian hypoplasia and Blake pouch remnant at mean of ≥23.1 weeks' gestational age. CONCLUSIONS: Dandy-Walker malformation can be described in relation to vermian hypoplasia and Blake pouch remnant by an increased tegmentovermian angle; however, other potential qualifying biometric measurements are more helpful at ≥23.1 weeks' gestational age. Because they fall along the same spectrum of abnormalities, the difficulty in distinguishing these entities from one another makes precise morphologic and biometric descriptions important.

The predictive and prognostic significance of cell-free DNA concentration in melanoma.

BACKGROUND: Melanoma is the leading cause of skin cancer-related deaths worldwide. While there have been significant improvements in the treatment of advanced melanoma in the past decade, biomarker development lagged behind. OBJECTIVES: The majority of liquid biopsy biomarkers rely on the analyses of oncogenic mutations; however, about 20% of melanoma patients are wild type. Therefore, validation of universal predictive and prognostic biomarkers is urgently needed. METHODS: We analysed plasma samples in a discovery cohort (n = 20) and expansion cohort (n = 166) of metastatic melanoma patients and healthy donors (n = 116). Total plasma circulating cell-free DNA (cfDNA) concentrations were measured on the Qubit® platform using assays for single-(ss) and double (ds)-stranded DNA, DNA spectrophotometry and RNase P qPCR. We explored the diagnostic, predictive and prognostic potential of cfDNA concentration by bio-statistical methods and established a cfDNA threshold for risk stratification. RESULTS: Our selected best method was Qubit® dsDNA assay which quantified higher plasma cfDNA concentrations in melanoma patients than in healthy controls (AUC 72%). Measurement of baseline cfDNA concentration revealed that high cfDNA was associated with presence of metastases and higher AJCC stage (P < 0.05). Furthermore, high baseline cfDNA was an indicator of shorter overall survival in patients with oncogenic mutations (HR 2.12, P = 0.0008), and in wild-type patients (HR 5.55, P < 0.0001). CONCLUSIONS: We provide evidence that total cfDNA can be used as a biomarker for melanoma irrespective of the tumour genotype and can provide information on tumour load, risk of progression and risk of death.

Elevated baseline serum PD-1 or PD-L1 predicts poor outcome of PD-1 inhibition therapy in metastatic melanoma.

BACKGROUND: Programmed cell death protein 1 (PD-1) checkpoint inhibition has recently advanced to one of the most effective treatment strategies in melanoma. Nevertheless, a considerable proportion of patients show upfront therapy resistance and baseline predictive biomarkers of treatment outcome are scarce. In this study we quantified PD-1 and programmed death-ligand 1 (PD-L1) in baseline sera from melanoma patients in relation to therapy response and survival. PATIENTS AND METHODS: Sera taken at therapy baseline from a total of 222 metastatic melanoma patients (two retrospectively selected monocentric discovery cohorts, n = 130; one prospectively collected multicentric validation cohort, n = 92) and from 38 healthy controls were analyzed for PD-1 and PD-L1 concentration by sandwich enzyme-linked immunosorbent assay. RESULTS: Melanoma patients showed higher serum concentrations of PD-1 (P = 0.0054) and PD-L1 (P < 0.0001) than healthy controls. Elevated serum PD-1 and PD-L1 levels at treatment baseline were associated with an impaired best overall response (BOR) to anti-PD-1 (P = 0.014, P = 0.041), but not to BRAF inhibition therapy. Baseline PD-1 and PD-L1 serum levels correlated with progression-free (PFS; P = 0.0081, P = 0.053) and overall survival (OS; P = 0.055, P = 0.0062) in patients who received anti-PD-1 therapy, but not in patients treated with BRAF inhibitors. By combining both markers, we obtained a strong discrimination between favorable and poor outcome of anti-PD-1 therapy, with elevated baseline serum levels of PD-1 and/or PD-L1 associated with an impaired BOR (P = 0.037), PFS (P = 0.048), and OS (P = 0.0098). This PD-1/PD-L1 combination serum biomarker was confirmed in an independent multicenter validation set of serum samples prospectively collected at baseline of PD-1 inhibition (BOR, P = 0.019; PFS, P = 0.038; OS, P = 0.022). Multivariable Cox regression demonstrated serum PD-1/PD-L1 as an independent predictor of PFS (P = 0.010) and OS (P = 0.003) in patients treated with PD-1 inhibitors. CONCLUSION: Our findings indicate PD-1 and PD-L1 as useful serum biomarkers to predict the outcome of PD-1 inhibition therapy in melanoma patients and to select patients for PD-1-based versus BRAF-based therapy strategies.

Early suppression of peripheral mononuclear blood cells in sepsis in response to stimulation with cytomegalovirus, OKT3, and pokeweed mitogen.

Critically ill patients are at risk for sepsis, and immunosuppressive mechanisms may prevail. Whether functional tests are helpful to detect immune alterations is largely unknown. Therefore, we tested the hypotheses that reactivity of peripheral blood mononuclear cells (PBMCs) to secrete interferon-γ (IFNγ) following stimulation in vitro is decreased in patients with early sepsis compared with postoperative patients. IFNγ secretion [enzyme-linked immunospot (ELISpot)] in response to stimulation with cytomegalovirus (CMV), pokeweed mitogen (PWM), muromonab-anti-CD3 (OKT3), and human leukocyte antigen (HLA)-DRA-mRNA expression and serum cytokine concentrations were repeatedly [days 1, 3, 5, and 7 after intensive care unit (ICU) admission] determined in patients with sepsis (n = 7) and patients undergoing major abdominal surgery (radical prostatectomy, cystectomy, n = 10). In a second cohort, HLA-DRA expression was assessed in 80 patients with sepsis, 30 postoperative patients, and 44 healthy volunteers (German clinical trials database no. 00007694). In patients with sepsis, IFNγ secretion (ELISpot) was decreased compared with controls after stimulation with CMV (P = 0.01), OKT3 (P = 0.02), and PWM (P = 0.02 on day 5), whereas unstimulated IFNγ secretion did not differ. HLA-DRA expression was also significantly decreased in patients with sepsis at all time points (P = 0.004) compared with postoperative surgical patients, a finding confirmed in the larger cohort. Reactivity of PBMCs to stimulation with CMV, PWM, and OKT3 as well as HLA-DRA expression was already decreased upon ICU admission in patients with sepsis when compared with postoperative controls, suggesting early depression of acquired immunity. ELISpot assays may help to clinically characterize the time course of immunocompetence in patients with sepsis.NEW & NOTEWORTHY We observed suppression of reactivity to stimulation with cytomegalovirus, muromonab-anti-CD3, and pokeweed mitogen in mononuclear blood cells of patients with early sepsis when compared with postoperative controls. Thus, there is early depression of acquired immunity in sepsis. Enzyme-linked immunospot assays may help to characterize immunocompetence in patients with sepsis.

CMR-guidance of passively tracked endomyocardial biopsy in an in vivo porcine model.

Endomyocardial biopsy (EMB) is considered to be the diagnostic gold-standard in detection of myocardial-inflammation. EMB is usually conducted under fluoroscopy without any specific target information. Specific target-information provided by cardiovascular magnetic resonance (CMR) may improve specificity of EMB. The aim was to investigate feasibility and safety of CMR-guided and targeted EMB in a preclinical-model using passively-tracked devices. Procedures were performed on a MRI-System equipped with an Interventional Software-Platform for real-time imaging. Ex vivo experiments were conducted to optimize visibility of the guide-sheath. In vivo experiments were conducted in 2 pigs for technical feasibility assessment and in 4 pigs after acute myocardial infarction to test feasibility of guided and lesion targeted EMB. For anatomical real-time imaging a single-shot-balanced-SSFP-sequence was applied. Myocardial targets were identified under real-time imaging (single-shot-T2 (sshT2) and single-shot Late-Gadolinium-Enhancement (sshLGE) sequences). Ex vivo experiments demonstrated best visibility of continuously labelled guide-sheath. CMR-guided EMB was feasible in all cases without major complications. Likewise, lesion-targeting endomyocardial biopsy was feasible in two cases. Biopsies exhibited appropriate sizes and qualities. Real-time lesion sequences revealed comparable CNR values to clinical-protocols. Real-time imaging of lesions showed following signal- and contrast-to-noise ratios (SNR/CNR): SNR of sshT2- and sshLGE was 124 ± 35 and 67 ± 51 respectively, whereas CNR was 81 ± 30 and 57 ± 44. This study demonstrates feasibility and safety of CMR-guided and basically targeted EMB with passively-tracked devices. Signal-to-noise ratios of real-time sequences is non-inferior to standard sequences for lesion detection. CMR-guidance may improve diagnostic accuracy of EMB since CMR can detect myocardial-targets under real-time-imaging.

Anti-HLA alloantibodies of the IgA isotype in re-transplant candidates part II: Correlation with graft survival.

We reported previously on the widespread occurrence of anti-HLA alloantibodies of the IgA isotype (anti-HLA IgA) in the sera of solid-organ re-transplantation (re-tx) candidates (Arnold et al., ). Specifically focussing on kidney re-tx patients, we now extended our earlier findings by examining the impact of the presence and donor specificity of anti-HLA IgA on graft survival. We observed frequent concurrence of anti-HLA IgA and anti-HLA IgG in 27% of our multicenter collective of 694 kidney re-tx patients. This subgroup displayed significantly reduced graft survival as evidenced by the median time to first dialysis after transplantation (TTD 77 months) compared to patients carrying either anti-HLA IgG or IgA (TTD 102 and 94 months, respectively). In addition, donor specificity of anti-HLA IgA had a significant negative impact on graft survival (TTD 74 months) in our study. Taken together, our data strongly indicate that presence of anti-HLA IgA, in particular in conjunction with anti-HLA-IgG, in sera of kidney re-tx patients is associated with negative transplantation outcome.

Effect of ABO incompatibility on T-cell flow cytometry cross-match results prior to living donor kidney transplantation.

BACKGROUND: Due to its high sensitivity, the flow cytometry cross-match (FCXM) has been described as valuable tool for identifying an optimal donor. We here focused on the impact of ABO incompatibility on FCXM results. METHODS: We analyzed 29 ABO incompatible and 89 ABO compatible donor-recipient pairs (73 and 175 datasets, respectively) prior to living donor kidney transplantation. In all patients, lymphocytotoxic cross-matches for B and T cells were negative. RESULTS: Recipients with blood group O (A to O and B to O) displayed significantly (P < 0.05) higher T-FCXM results than those with blood group A and B (A to B, B to A and AB to A), respectively. Donor-specific T-FCXM responses (ΔMFI values) were significantly higher (P < 0.05) in ABO incompatible vs. compatible pairs (ABO incompatible recipients with blood group O: 32 ± 6; with blood group A: 19 ± 7; with blood group B: 7 ± 4; recipients with ABO compatibility: 3 ± 2, respectively, data represent mean ± SEM). Consistent with the T-FCXM results donor-specific isohemagglutinins (IgG titers) were significantly higher in recipients with blood group O vs. A, both prior to rituximab treatment and plasmapheresis/immune adsorption (P = 0.004) and immediately prior to transplantation, i.e., after rituximab and antibody-depleting therapies (P = 0.04). CONCLUSIONS: ABO incompatibility was associated with higher T-FCXM responses, especially in recipients with blood group O. This finding has major impact on the interpretation of flow cross-match results. Current cut-off values need to be reassessed in the ABO incompatible setting. © 2016 International Clinical Cytometry Society.

T2 mapping cardiovascular magnetic resonance identifies the presence of myocardial inflammation in patients with dilated cardiomyopathy as compared to endomyocardial biopsy.

Aims: The aim of this study was to determine the value of T2 mapping for the non-invasive assessment of myocardial inflammation in different stages of systolic left ventricular dysfunction in dilated cardiomyopathy (DCM) in comparison with endomyocardial biopsy (EMB). Methods and results: A total of 132 subjects were enrolled between 2013 and 2016 (62 controls and 70 patients with DCM). All patients underwent CMR at 1.5 T and received coronary angiogram and EMB. CMR applied standard protocols including T2 mapping with Gradient And SpinEcho sequence (GRASE). Global T2 relaxation time was significantly increased in patients with DCM compared to the healthy controls (T2 time DCM vs. controls: 65.9 ± 6.2 vs. 60.0 ± 4.2 ms; P < 0.001). Of note, patients with the presence of inflammatory cells in EMB exhibited further elevation of T2 values (T2 time in patients with the presence of inflammatory cells vs. T2 time in patients without: 68.8 ± 5.8 vs. 64.7 ± 5.9 ms; P = 0.02). Receiver operating characteristic analysis of our data deciphered a global myocardial T2 time >65.3 ms as the best cut-off for distinction between the healthy controls and patients with myocardial inflammation [sensitivity 93%, specificity 90%, P < 0.01, area under the curve (AUC) 0.95]. In patients with DCM, this threshold identified patients with biopsy-proven inflammation with a sensitivity of 79% and specificity 58% (AUC 0.72). Conclusion: In patients with DCM and presence of inflammatory cells in the myocardium, myocardial T2 relaxation times may help to non-invasively detect myocardial inflammation. Although there is an overlap of T2 values between patients and healthy controls, T2 mapping may facilitate the identification of patients who may benefit from EMB for therapeutic decision-making.

Primary central nervous system vasculitis and its mimicking diseases - clinical features, outcome, comorbidities and diagnostic results - A case control study.

OBJECTIVES: To compare clinical features and outcome, imaging characteristics, biopsy results and laboratory findings in a cohort of 69 patients with suspected or diagnosed primary central nervous system vasculitis (PCNSV) in adults; to identify risk factors and predictive features for PCNSV. PATIENTS AND METHODS: We performed a case-control-study including 69 patients referred with suspected PCNSV from whom 25 were confirmed by predetermined diagnostic criteria based on biopsy (72%) or angiography (28%). Forty-four patients turned out to have 15 distinct other diagnoses. Clinical and diagnostic data were compared between PCNSV and Non-PCNSV cohorts. RESULTS: Clinical presentation was not able to discriminate between PCNSV and its differential diagnoses. However, a worse clinical outcome was associated with PCNSV (p=0.005). Biopsy (p=0.004), contrast enhancement (p=0.000) or tumour-like mass lesion (p=0.008) in magnetic resonance imaging (MRI), intrathecal IgG increase (p=0.020), normal Duplex findings of cerebral arteries (p=0.022) and conventional angiography (p 0.010) were able to distinguish between the two cohorts. CONCLUSION: In a cohort of 69 patients with suspected PCNSV, a large number (64%) was misdiagnosed and partly received treatment, since mimicking diseases are very difficult to discriminate. Clinical presentation at manifestation does not help to differentiate PCNSV from its mimicking diseases. MRI and cerebrospinal fluid analysis are unlikely to be normal in PCNSV, though unspecific if pathological. Cerebral angiography and biopsy must complement other diagnostics when establishing the diagnosis in order to avoid misdiagnosis and mistreatment. CLINICAL TRIAL REGISTRATION: German clinical trials register: http://drks-neu.uniklinik-freiburg.de/drks_web/, Unique identifier: DRKS00005347.

[Procedures on patients receiving NOACs : What's possible?] / Eingriffe unter NOAK : Was ist möglich?

Non-vitamin K antagonist oral anticoagulants (NOACs) are increasingly used in patients with deep vein thrombosis (DVT), pulmonary embolism (PE) and atrial fibrillation (AF). However, there is insufficient data concerning the periinterventional, perioperative, and intensive care management of patients on NOACs. Therefore, the recommendations regarding this management rely on pharmacokinetics of the particular NOAC in combination with the individual patient's characteristics, bleeding risk of the planned intervention/surgery, and urgency of the procedure. This review summarizes evidence and recommendations regarding the optimal periinterventional/perioperative antithrombotic management of patients on NOACs.

Humoral and Cellular Responses to a Single Dose of Fendrix in Renal Transplant Recipients with Non-response to Previous Hepatitis B Vaccination.

Approximately 70% of kidney transplant recipients are non-responders to conventional hepatitis B virus (HBV) vaccines. We examined whether Fendrix™, an HBV vaccine containing 3-O-desacyl-4'-monophosphoryl lipid A (MPL) as adjuvant, could induce HBV immunity in these patients and compared their vaccination efficacy with healthy controls tested previously by the same assays. We selected 35 kidney transplant recipients who had been vaccinated at least thrice against HBV but had never displayed anti-HBs antibodies. We re-assessed their anti-HBs antibody titres and further determined cellular HBV immunity by proliferation assay and interferon (IFN)-γ ELISpot. Seventeen recipients did neither display humoral nor cellular immunity and could be tested prior to and at month 1 after vaccination. Of note, HLA antigens associated with non-response to HBV vaccination (HLA-DRB1*03 and HLA-DQB1*02) were over-represented in these 17 recipients. At month 1 after a single vaccination with Fendrix™, we observed a significant increase in anti-HBs antibodies (P = 0.02). In seven of 17 recipients, we detected anti-HBs antibodies ≥10 IU/l (10-264), in four HBV-specific lymphocyte proliferation (stimulation index of 2.6-8.7) and in one specific IFN-γ responses (12 spots increment). The vaccination response to Fendrix™ was significantly higher (P = 0.035) than the response to HBVaxPro™ in young healthy controls. In summary, the results show that a single vaccination with Fendrix™ could already induce HBV-specific humoral and/or cellular responses in ten of 17 kidney transplant patients. Thus, Fendrix™ appears as an efficient vaccine in this patient cohort.

Diagnostics and treatment of a severe humoral rejection after liver transplantation: donor-specific antibodies as a still underestimated cause of graft failure.

BACKGROUND: Donor-specific antibodies (DSAs) are increasingly being considered a cause of complications after liver transplant (LT). However, neither monitoring of DSAs nor the appropriate therapeutic procedures for humoral graft damage are yet standardized. Here we report a case of DSA-positive humoral rejection after LT that was successfully treated with plasmapheresis and immunoglobulins. METHODS: Human leukocyte antigen (HLA)-specific DSAs were detected by Luminex bead assay. Patient characteristics, laboratory values, and data about the patient's general condition were documented from April 2013 to June 2015. CASE REPORT: Eighteen months after LT, a 54-year-old man experienced severe hepatopathy with rapidly increasing transaminase activity and total bilirubin levels. Histologic findings were inconclusive, demonstrating chronic cholestasis and minimal positive staining for C4 d. However, an analysis for anti-HLA antibodies detected DSAs against HLA class II molecules with high mean fluorescence intensity. The patient underwent 8 courses of plasmapheresis, resulting in sustained amelioration of his condition and decreases in bilirubin levels and transaminase activity. CONCLUSION: De novo DSAs can be responsible for graft failure after LT. Thus, procedures aimed at detecting DSAs are recommended, and regular monitoring of DSAs after LT is important for individualized risk management. Plasmapheresis is an efficient therapeutic procedure for DSA-associated graft failure.

Diets of deepwater oreos (Oreosomatidae) and orange roughy Hoplostethus atlanticus.

The diets of black oreo Allocyttus niger, smooth oreo Pseudocyttus maculatus, spiky oreo Neocyttus rhomboidalis and orange roughy Hoplostethus atlanticus were determined from examination of contents of 240, 311, 76 and 415 non-empty stomachs, from fishes sampled by bottom trawl on Chatham Rise to the east of South Island, New Zealand. Hoplostethus atlanticus had an opportunistic predatory strategy with a broad diet dominated by prawns and mesopelagic teleosts, but with substantial components of mysids and cephalopods. Pseudocyttus maculatus was strongly specialized on gelatinous zooplankton (jellyfish and salps). Allocyttus niger consumed mainly salps and hyperiid amphipods, and to a lesser extent fishes, prawns, mysids and copepods. Neocyttus rhomboidalis primarily consumed salps, along with mysids, euphausiids and fishes. Only P. maculatus did not exhibit significant ontogenetic variation in diet. The diets were also influenced by year and bottom depth. Differences in the distributions and diets of the four species probably reduce conflicts in resource use.

Fetuin A is a Predictor of Liver Fat in Preoperative Patients with Nonalcoholic Fatty Liver Disease.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) and steatohepatitis (NASH) are frequent comorbidities in perioperative patients. However, the predictive role of the hepatokine fetuin A was not evaluated in this collective. OBJECTIVE: To study fetuin A as predictor of NAFLD/NASH in preoperative patients. METHODS: 58 subjects were included. Fetuin A was studied in patients undergoing open abdominal surgery and in a subset with acute liver failure. Blood and liver specimens were sampled. NAFLD was histologically evaluated. Liver fat was additionally analyzed by an enzymatic approach, circulating fetuin A by enzyme linked-immunosorbent assay, fetuin A mRNA by reverse-transcription PCR. RESULTS: Univariate correlation studies linked fetuin A to liver steatosis (r = 0.40, p = .029) and hepatocellular ballooning degeneration (r = 0.34, p = .026). Compared to non-NAFLD subjects fetuin A was increased in NAFLD (p = .009) and in NASH (p = .029). However, when corrected for main confounders by linear modeling, fetuin A remained related to hepatic steatosis, but not to ballooning degeneration or other NAFLD features. In support of this, biochemically analyzed liver lipids correlated with fetuin A in plasma (r = 0.34, p = .033) and with hepatic fetuin A mRNA (r = 0.54, p < .001). In addition, plasma fetuin A was related to hepatic mRNA (r = 0.32, p = .036), while circulating levels were reduced by 64% with acute liver failure (p < .001), confirming the liver as main fetuin A source. CONCLUSION: Fetuin A is suggested as noninvasive biomarker of hepatic steatosis in preoperative settings.

A Rare Case of Isolated Cerebral Sarcoidosis Presenting as Suprasellar Mass Lesion with Salt-Wasting Hypopituitarism.

Background Sarcoidosis is a systemic disorder of unknown origin characterized by noncaseating granulomas. Clinical symptoms due to central nervous system (CNS) involvement occur in 5 to 7% of all cases; subclinical involvement is more frequent. Sole CNS involvement is very rare. Case Report A 25-year-old man presented with increasing polyuria and polydipsia over 8 weeks. Magnetic resonance imaging (MRI) revealed a supra- and infra-chiasmatic pre-thalamic mass lesion 1.0 × 1.4 × 1.4cm in diameter. Microsurgical biopsy verified a necrotizing noncaseating epithelioid cell tumor indicative for neurosarcoidosis. All symptoms dissolved within 3 months under stringent corticoid therapy. Conclusion Intracranial mass lesions as the primary and only manifestation of neuronal sarcoidosis are rare. Because conservative treatment is safe and effective, surgery is limited to biopsy and the alleviation of pressure-related symptoms to preserve neurologic function.

Rowing increases stroke volume and cardiac output to a greater extent than cycling.

Exercise stimulates increases in heart rate (HR), stroke volume (SV) and cardiac output (CO). These adaptive mechanisms are strongly dependent on the type of exercise. Both rowing and cycling are widely used for physical training worldwide; however, evidence regarding the differences in major hemodynamic parameters during rowing and cycling remains insufficient. Ten healthy male volunteers were randomly assigned to perform either a rowing or cycling exercise. After 20 min rest, the group who had rowed first performed the cycling exercise and vice versa. Exercise was performed at a power-to-weight ratio of 2 W/kg for 2 min. HR, SV, CO and blood pressure (BP) were measured noninvasively using pulse-wave analysis at baseline and immediately after each exercise. HR, SV and CO were significantly higher after exercise than at rest. Whereas HR was comparable between rowing and cycling, SV and CO were significantly higher after rowing than after cycling. BP was comparable among all three measurements. Rowing increased SV and CO to a greater extent than cycling, whereas HR and BP were not influenced by the type of exercise. Our data suggest that rowing leads to more extensive stimulation of cardiac contractility and/or decreases in peripheral vascular resistance compared with cycling.

Routine exercise alters measures of immunity and the acute phase reaction.

PURPOSE: To expand our understanding of the overall anti-inflammatory nature of routine exercise; we compared resting blood values from adults who habitually undertake frequent, moderate levels of exercise to reference interval values assumed to reflect values largely from non-exercisers. This information would be useful for clinicians interpreting blood tests assessing inflammatory, immune and acute phase responses. METHODS: Blood samples were collected from 119 community adult self-reported routine exercisers (61 males and 58 females aged 18-60 years). Samples were analysed for 20 cellular and non-cellular biomarkers which included 11 immunological and 9 acute phase reactants. These data were compared to reference intervals from the same hospital laboratory that performed the analyses on our participants' samples. Individual analyte values were also compared with participants' self-reported 150 day exercise patterns which included exercise frequency, intensity and duration. RESULTS: In general, mean values for routine exercise participants fell at the lower end of laboratory reference interval for most inflammatory analytes. More than 10 % of participants had numbers of CD19(+), CD8(+) and 16/56(+) NK cells below the low end of the respective reference interval. More than 10 % of observed acute phase reactant values (for C3, haptoglobin and ferritin) were also below the low end of the reference interval. At rest IgM (r = -0.22) and IgG (r = -0.31) values correlated negatively (p < 0.05) with exercise load. CONCLUSIONS: Routine exercise appears to lower resting numbers of a variety of immune cell-types as well as the concentration of several classical acute phase reactants. These wide-ranging systemic effects are presumably adaptive changes, not pathology and collectively confirm the well-reported and clinically important anti-inflammatory effects of exercise.