Monocyte subpopulations for non-invasive differentiation of non-alcoholic fatty liver and steatohepatitis

Hintergrund: Die Nicht-alkoholische Fettlebererkrankung (NAFLD) ist die häufigste Ursache chronischer Lebererkrankungen (Day, 2005, Shaker et al., 2014) und stellt, aufgrund ihrer engen Assoziation mit Adipositas, Diabetes Mellitus II und dem Metabolischen Syndrom, zunehmend eine Herausforderung in den westlichen Gesundheitssystemen dar. Die NAFLD wird in zwei große Untergruppen unterteilt: die simple Steatose (NAFL) und die nicht-alkoholische Steatohepatitis (NASH). NASH kann zu ernsthaften Komplikationen bis hin zu Leberzirrhose, chronischem Leberversagen und Leberzellkarzinom führen (Clark and Diehl, 2003, Bugianesi et al., 2002). Erst kürzlich konnte eine Verbindung zwischen einer Erhöhung der Gesamt-Monozyten, einer leberspezifischen Monozyten-Rekrutierung sowie einer Erhöhung der Monozyten-spezifischen Chemotaktine und NAFLD im Speziellen gezeigt werden, was die Monozyten als prognostische Biomarker für NAFLD interessant erscheinen lässt (Karlmark et al., 2009, Haukeland et al., 2006, Wang et al., 2016). Studien Rationale: Trotz der hohen Prävalenz der NAFLD kann eine Differenzierung von NAFL und NASH bis dato nur anhand einer invasiven und kostspieligen Leberbiopsie erfolgen. Eine nicht-invasive Diagnostik der NAFLD ist nicht nur für die PatientInnen-Compliance von großer Bedeutung, sondern ebenso für eine frühzeitige Diagnose und adäquate (Nach-) Betreuung. Umso wichtiger noch erscheint die nicht-invasive Differenzierung von NAFL und NASH, angesichts der sehr unterschiedlichen Prognosen. Hierfür werden nicht-invasive Biomarker benötigt. Ziel: Das Ziel unserer Studie war es herauszufinden, ob Monozyten-Subpopulationen sich für die nicht-invasive Diagnostik von NAFLD und des Weiteren zur Differenzierung von NAFL und NASH in einem bariatrischen Patientenkollektiv eignen. Patienten und Methodik: Zwischen 07/2015 und 05/2017 wurden konsekutiv 93 adipöse PatientInnen, welche für eine bariatrische Operation vorgesehen waren sowie prä-operativ mittels Ultraschall mit einer nicht-alkoholischen Fettleber diagnostiziert wurden, sowie auch 27 gesunde nicht-adipöse Kontroll-Patienten, eingeschlossen. Die Monozyten-Subpopulationen wurden aus EDTA-Vollblut gemessen und mit den jeweiligen, intraoperativ gewonnenen Leberbiopsien verglichen. Ergebnisse: Wir konnten einen signifikanten Unterschied der einzelnen Monozyten Subpopulationen zwischen den Gruppen sowohl in absoluten als auch relativen Zahlen, sowie auch in der mittleren Fluoreszenz ihrer Oberflächenmarker zeigen. Der beste Marker für eine NAFLD (AUC 0.861) war hierbei die absolute Anzahl der intermediären Monozyten und der beste Marker für eine NASH die Ratio von klassischen zu intermediären Monozyten (AUC 0.706). Schlussfolgerung: Monozyten-Subpopulationen eignen sich zur nicht-invasiven Diagnostik der NAFLD bzw. der NASH. Der Entzündungsprozess im Rahmen einer NASH scheint in der starken Aktivierung der Monozyten reflektiert zu sein.Background: Non-alcoholic fatty liver disease (NAFLD) is considered to be the most common cause of chronic liver disease (Day, 2005) (Shaker et al., 2014) and, due to its tight association with obesity, type II diabetes mellitus as well as the metabolic syndrome (MS), proves to be an increasing problem in todays Western healthcare systems. NAFLD can be subdivided into two major groups: the benign non-alcoholic fatty liver (NAFL) and the potentially progressive non-alcoholic steatohepatitis (NASH). NASH can present with complications as severe as liver cirrhosis, chronic hepatic failure and hepatocellular carcinoma (Clark and Diehl, 2003) (Bugianesi et al., 2002). Recently, an increased total monocyte fraction, hepatic monocyte recruitment as well as elevated monocyte-specific chemotactic cytokines were linked to not only liver damage, but also NAFLD specifically, and therefore were suggested as prognostic biomarkers in NAFLD patients (Karlmark et al., 2009) (Haukeland et al., 2006) (Wang et al., 2016). Study Rationale: Despite the high prevalence of NAFLD, to date, reliable differentiation of NAFL and NASH is only possible performing an invasive and costly liver biopsy. The non-invasive detection of NAFLD is not only crucial for patient compliance, but also for diagnosis, early detection and follow-ups. All the more necessary is the non-invasive differentiation of NAFL and NASH, since both present with a different prognosis and outcome. Therefore, non-invasive biomarkers are needed. Aim: In this study, our aim was to investigate whether monocyte subpopulations are able to detect NAFLD in general and furthermore differentiate between NAFL and NASH in a patient collective of bariatric patients. Patients and methods: From 07/2015 to 05/2017 we consecutively included 93 patients with obesity who were scheduled for elective bariatric surgery and were pre-operatively diagnosed with non-alcoholic hepatic steatosis by the means of ultrasound as well as laboratory testing, to exclude other causes of chronic liver disease. We furthermore included 27 healthy non-obese controls. The monocyte subpopulations were measured from each patients whole blood and the results were matched to the histology reports of intra-operatively performed liver biopsies. Results: We found a significant difference within the monocyte subpopulations in absolute numbers, relative numbers and mean fluorescence comparing groups. The best marker for NAFLD (AUC 0.861) was the absolute number of intermediate monocytes and the best marker for NASH was the ratio of classical to intermediate monocytes (AUC 0.706). Conclusion: Monocyte subpopulations are a suitable non-invasive biomarker for die diagnosis of NAFLD and NASH. The inflammation process during the development of NASH seems to be reflected by the strong activation of monocytes.Abweichender Titel laut Übersetzung der Verfasserin/des VerfassersArbeit an der Bibliothek noch nicht eingelangt - Daten nicht geprüftMedizinische Universität Wien, Diplomarb., 2018(VLID)256583

A retrospective analysis of venous thromboembolism trends in chemotherapy‐induced anemia: Red blood cell transfusion versus erythrocyte stimulating agent administration

Abstract Background Patients receiving a variety of chemotherapy regimens often develop chemotherapy‐induced anemia (CIA), which contributes to poor outcomes including increased mortality. Prompt and effective treatment of CIA is essential to prevent fewer chemotherapy dose delays and reductions. Optimal therapy of CIA is controversial and involves the solitary and combined use of intravenous iron, red blood cell (RBC) transfusions, and erythropoietin stimulating agents (ESAs). Despite the baseline coagulopathies present in patients with malignancy, administration of both RBC transfusions and ESAs is associated with venous thromboembolism (VTE). It remains unknown whether the risk of VTE in patients with CIA is greater among patients who receive RBC transfusions or ESAs. Methods A retrospective study analyzed 10,269 University of Pennsylvania Health System patients with malignancies of various type, stage, and histopathology who developed CIA between 2008 and 2017. Using multivariate Cox regression, we determined adjusted hazard ratios (and corresponding 95% confidence intervals) of VTE development after adjusting for RBC and ESA intervention (all during the 90 days following CIA diagnosis). Results Among the 10,269 patients with CIA, 2,642 (25.7%) developed a VTE within the 90‐day period. VTE risk following RBC transfusion (HR = 1.37, 95% CI 1.24‐1.50, P < .001) was more than twice as common as VTE risk following ESA administration (HR = 0.53, 95% CI 0.40‐0.69, P < .001). Conclusion While both RBC transfusion and ESA are independently associated with VTE, our data suggest a greater risk of VTE development with RBC transfusion as compared with ESA

Medical, Technical and Audiological Outcomes of Hearing Rehabilitation with the Bonebridge Transcutaneous Bone-Conduction Implant: A Single-Center Experience

Bone-conduction implants are a standard therapeutic option for patients with conductive, unilateral, or mixed hearing loss who either do not tolerate conventional hearing aids or can benefit from surgery. The aim of this study was to evaluate long-term medical and technical outcomes, and audiological results with the Bonebridge transcutaneous bone-conduction implant. This retrospective study included all patients implanted with a bone-conduction hearing implant at a tertiary medical referral center between March 2012 and October 2018. Medical and technical outcomes included the mean length of implant usage, medical and technical complications (skin and wound infection, lack of benefit, technical failure), explantations and revisions, coupling approaches, implant failure rate, implant survival and the implant loss for added follow-up years. Auditory results were measured by functional hearing gain and the Freiburger monosyllabic test at 65 dB sound pressure level. Sixty-four patients were included in the study; five of these were implanted bilaterally (69 devices). Five unilaterally implanted patients were lost to follow-up. The mean follow-up was 27.1 months (range: 0.2 months&ndash;6.3 years). The mean implant usage was 25.9 months (range: 0.2 months&ndash;6.3 years). Fifty-seven implants (89.1%) were in use at the end of the follow-up period. Complications occurred in six ears (9.4%). Five implants (7.8%) were explanted without reimplantation. Device failure occurred in one implant (1.6%), which was possibly caused by recurrent head trauma. The rate of implant loss due to technical device failure (damage to device) was 1 per 72 follow-up years. The mean improvement on the Freiburger monosyllabic test (52.1%, p = 0.0001), and in functional hearing gain across frequencies (26.5 dB, p = 0.0001) was significant. This single-center follow-up reveals the medical and technical reliability of a transcutaneous bone-conduction implant for hearing rehabilitation because complication and revision rates were low. The majority of patients still used the device at the end of the observation period. Implantation resulted in favorable hearing outcomes in comparison to that of unaided conditions. Cautious patient selection mainly regarding co-morbidities, the history of chronic otologic diseases and proper surgical technique seems to be crucial in reducing complications

Complement Factor C5a Is Increased in Blood of Patients with Abdominal Aortic Aneurysm and Has Prognostic Potential for Aneurysm Growth

In this observational case-control study, circulating levels of complement factors C3a and C5a and leukotriene B4 (LTB4) were analysed in abdominal aortic aneurysm (AAA) patients regarding their association with diagnosis and prognosis. Serum C5a was significantly raised in AAA patients compared to healthy controls—median 84.5 ng/ml (IQR = 37.5 ng/ml) vs. 67.7 ng/ml (IQR = 26.2 ng/ml), p = 0.007—but was not elevated in patients with athero-occlusive disease. Serum C5a levels correlated significantly with the increase in maximum AAA diameter over the following 6 months (r = 0.319, p = 0.021). The median growth in the lowest quartile of C5a ( 101 ng/ml): 1.0 mm/6 months (IQR = 0.8 mm) vs. 2.0 mm/6 months (IQR = 1.5 mm), p = 0.014. A log-linear mixed model predicted AAA expansion based on current diameter and C5a level. To our knowledge, this is the first study linking complement activation, in particular C5a serum level, with AAA progression. [Image: see text] SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12265-020-10086-5

Langenbeck's Archives of Surgery / Effectiveness of anti-osteoporotic treatment after successful parathyroidectomy for primary hyperparathyroidism: a randomized, double-blind, placebo-controlled trial

Purpose After successful surgery for primary hyperparathyroidism, bone mineral density (BMD) does not improve equally in all patients. As no trial has so far aimed to influence normalization of BMD, it was the goal of this investigation to determine whether pharmacological treatment is effective in improving regain of BMD after successful parathyroidectomy in patients with preoperatively diagnosed osteoporosis or osteopenia and to evaluate when treatment may be indicated. Methods In this randomized, placebo-controlled, double-blind trial, 52 patients were treated with strontium ranelate 2 g daily + 1000 mg calcium + 800 IU vitamin D (strontium group; SG) or with 1000 mg calcium + 800 IU vitamin D alone (placebo group; PG) for 1 year. The main outcome measures were BMD (lumbar spine, femoral neck, radius) and bone turnover markers. Results The baseline characteristics were similar in both groups. Absolute BMD (1.007 0.197 vs. 0.897 0.137 g/cm; p = 0.024) and both relative (9.94 vs. 3.94%; p < 0.001) and absolute (0.09 0.06 vs. 0.03 0.04 g/cm; p < 0.001) changes in lumbar-spine BMD were significantly higher in the SG than in the PG. Compared to baseline, BMD significantly increased in both groups at the lumbar spine (p < 0.001 and p = 0.001, respectively) and femoral neck (both p < 0.001), whereas radius BMD only changed significantly in the SG. However, the proportion of patients with osteoporosis/osteopenia significantly declined only at the lumbar spine in the SG (from 69.0 to 37.9%; p = 0.034), whereas no decrease was found in the PG. No severe adverse events occurred. Conclusions Postoperative anti-osteoporotic treatment can positively influence regain of BMD mainly in the lumbar spine and should be considered. Without treatment, most patients and especially those with low preoperative markers of bone turnover remained osteoporotic/osteopenic 1 year after surgery.(VLID)496250

Total thyroidectomy (Tx) versus thionamides (antithyroid drugs) in patients with moderate-to-severe Graves ophthalmopathy a 1-year follow-up : study protocol for a randomized controlled trial

Background Graves disease (GD) is characterized by thyrotoxicosis and goiter and arises through circulating autoantibodies that bind to, and stimulate, the thyroid hormone receptor (TSHR). A temporal relation between the onset of hyperthyroidism and the onset of ophthalmopathy, a common extrathyroidal manifestation, has been demonstrated. Graves ophthalmopathy (GO) is typically characterized by an inflammation and expansion of the extraocular muscles and an increase in retroorbital fat. There are currently three forms of therapies offered for hyperthyroidism caused by Graves disease: antithyroid drugs (ATD) (thionamides), radioiodine ablation (RAI) and thyroidectomy (Tx). To date, there is no clear recommendation on the treatment of Graves disease and GO, mainly due to the individuality of the disease in each patient. The aim of the study is to examine the difference in the outcome of GO in patients with moderate-to-severe GO who receive Tx versus further ATD after suffering their first relapse of GO, or in which GO stays the same following the initial decrease in ATD therapy after 6 months. Methods/Design This prospective randomized clinical trial with observer-blinded analysis will analyze 60 patients with moderate-to-severe GO who receive Tx versus ATD without surgery. Main outcome variables include: muscle index measurements via ultrasound and thyroid antibody levels. Additional outcome variables include: Clinical Activity Score (CAScore), NOSPECS score, superonasal index measurements via ultrasound, and quality of life score. Discussion This study should allow for better therapeutic choices in patients with moderate-to-severe GO. In addition, it should demonstrate whether the outcome of GO in patients with moderate-to-severe GO is better in those who receive early Tx versus further ATD. Furthermore, this study will aim to establish a standard glucocorticoid scheme before and after Tx in patients with moderate-to-severe EO. Trial registration Eudra-CT: 2015003515-38; Medical University of Vienna Protocol Record 1839/2015. Date of Ethics Committee approval: 19 January 2017. Registered on 27 January 2017.(VLID)468223