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RESULTS After matching patients who had received vedolizumab with those who had received adalimumab, the rate of persistence after 3 therapy years was 30.3% for vedolizumab and 27.9% for adalimumab (log-rank p = 0.005). The corresponding figures were 27.8 and 20.8% in the vedolizumab-golimumab matched-pair analysis (log-rank p less then 0.001) and 29.5 and 25.2% in the vedolizumab-infliximab matched-pair analysis (log-rank p value = 0.008). Vedolizumab was associated with a significant 0.85-, 0.72-, and 0.86-fold decrease in the risk of discontinuation within 3 years of therapy initiation compared to adalimumab, golimumab, and infliximab, respectively. CONCLUSIONS Treatment persistence was higher for vedolizumab than for TNF-α inhibitors up to 3 years after initiating second-line biological therapy. © 2020 S. Karger AG, Basel.The optimal type of surgery (e.g., anatomic or non-anatomic resection) or radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC) is still under debate despite numerous comparative studies based on overall survival. This debate continues not only because these endpoints are influenced by non-surgical factors, such as liver function, but because the definition of non-anatomic resection for HCC has remained unclear. The optimal surgery could be logically determined based on the mechanism of local intrahepatic metastasis, that is, the drainage of tumour blood flow (TBF), because HCC spreads locally through tumour blood flowing to the peri-tumourous liver parenchyma. Since TBF is clearly demonstrated by CT scan under hepatic arteriography, the surgical margin can be determined individually based on the drainage of TBF without deteriorating local curability. Controversy regarding RFA and surgery does not result from the curability of treatment itself but from the lack of scientific evidence on safety margins. Based on proper concepts and self-evident truths, an algorithm of loco-regional treatment for HCC is proposed. © 2020 S. Karger AG, Basel.BACKGROUND Postmenopausal hormone therapy (HT) increases the risk of stroke. Here we evaluate whether leisure time physical activity (LTPA) can change stroke risk in women using HT, leveraging data from the California Teachers Study. METHODS Female California educators without a prior history of stroke (n = 118,294) were followed from 1995 through 2015 for stroke end points. Based on statewide hospitalization data, 4,437 women had ischemic (n = 3,162; International Classification of Diseases [ICD]-9 433, 434, 436) or hemorrhagic (n = 1,275; ICD-9 430-432, excluding 432.1) stroke. LTPA and HT use were evaluated at 2 time points (baseline [1995-1996] and 10-year follow-up [2005-2006]). LTPA was assessed using American Heart Association (AHA) recommendations (>150 min/week moderate or >75 min/week strenuous physical activity). Using multivariable Cox proportional hazards models, we estimated the hazard ratios (HRs) and 95% CIs for the associations between HT use and concurrent LTPA with incident stroke. RESULTS Compared to women who never used HT, stroke risk was highest among women who were current HT users and did not meet AHA recommendations for LTPA at the time of their HT use HRbaseline 1.28 (95% CI 1.13-1.44); HR10-year follow-up 1.17 (95% CI 0.91-1.50). Based on the baseline questionnaire, current HT users who met AHA recommendations for LTPA in 1995-1996 still had elevated stroke risk in the 20-year follow-up (HR 1.22, 95% CI 1.08-1.37). However, among current HT users who met AHA recommendations for LTPA at the 2005-2006 follow-up questionnaire, stroke risk was not elevated (HR 1.01, 95% CI 0.80-1.29). Evaluation of the 2 time points in concert further demonstrated that meeting AHA recommendations for LTPA at the most recent follow-up time point was required to reduce HT-related stroke risk. CONCLUSION Concurrent physical activity may attenuate the short-term increase in risk of stroke risk associated with HT use. © 2020 S. Karger AG, Basel.BACKGROUND Pegylated asparaginase may induce prolonged hypertriglyceridemia. To date, there is no standard management of this complication. Here, we present a case report of pegylated asparaginase-induced hypertriglyceridemia and hepatotoxicity successfully treated with continuous intravenous infusion of insulin and heparin. CASE PRESENTATION A 51-year-old male patient with lymphoid blast crisis of chronic myelogenous leukemia was treated with pegylated asparaginase. The patient developed severe hypertriglyceridemia. Supportive therapy with low-fat diet, fibric acids, and omega-3 fatty acids was not successful, and later, the patient developed high-grade hepatotoxicity. Like hypertriglyceridemia-induced pancreatitis, continuous intravenous infusion of insulin and heparin was initiated. The level of triglyceride and cholesterol decreased rapidly within 4 days. CONCLUSION In case of severe pegylated asparaginase-induced hypertriglyceridemia, continuous intravenous infusion of insulin and heparin can reduce rapidly and safely the triglyceride level. Controlled trials are needed to address this important issue. © 2020 S. Karger AG, Basel.AIM The skin represents a drug delivery portal. The establishment of a skin model capable of distinguishing between the follicular and intercellular penetration pathways remains a challenge. see more The study described herein was aimed at showing the influence of two nail varnishes as closure material and four application techniques to spread the active pharmaceutical ingredient (API) on a successful follicular closure without inducing penetration-enhancing effects. MATERIALS AND METHODS For all experiments, ex vivo porcine ear skin was used. In study design A, a standard and a solvent-free nail varnish were compared. It was tested whether the different application techniques (spreading with pipette, careful finger massage, 5-Hz finger massage, 5-Hz automatic massage) potentially destroy an intact follicular closure. Laser scanning microscopy imaging was used to measure if the model drug (fluorescein sodium salt) penetrated into the hair follicles. Study design B investigated how the penetration is affected when appluded. CONCLUSION This study clearly demonstrates that a standard nail varnish in combination with a gentle application technique of the API provides a secure follicular closure. The presented study only investigated the closure for the substances caffeine and fluorescein sodium salt. The results might not be transferable to all kinds of APIs. © 2020 S. Karger AG, Basel.OBJECTIVE The aim of this work was to determine the effect of miR-375 on chondrocyte metabolism and oxidative stress in osteoarthritis (OA) mouse models through the JAK2/STAT3 signaling pathway. METHODS Chondrocytes were divided into control, IL-1β, IL-1β + miR-375 mimic, IL-1β + miR-375 inhibitor, IL-1β + miR-NC (negative control), and IL-1β + miR-375 inhibitor + siJAK2 groups. The chondrocyte proliferation was determined by MTT assay, the superoxide dismutase (SOD) and malondialdehyde (MDA) levels by corresponding kits, and the chondrocyte apoptosis by TUNEL staining. Furthermore, OA mouse models were divided into Sham, OA + miR-NC, and OA + miRNA-375 antagomir groups. The pathological changes were observed, and the expressions of miR-375 and the JAK2/STAT3 pathway were determined by qRT-PCR and Western blotting, respectively. RESULTS IL-1β-induced chondrocytes had significant increases in miR-375 and MDA, with decreased proliferation and SOD levels, as compared to the control group. Meanwhile, they also exhibited elevated apoptosis, with upregulations of ADAMTS-5 and MMP-13 and downregulations of COL2A1 and ACAN, as well as decreased p-JAK2/JAK2, p-STAT3/STAT3, and Bcl-2/Bax. However, these changes were significantly improved after transfection with miR-375 inhibitor, but transfection with miR-375 mimic resulted in severer exacerbation. Notably, the improvement of miR-375 inhibitor could be abolished by transfection with siJAK2. Furthermore, miR-375 antagomir significantly alleviated OA progression in OA mice in vivo. CONCLUSION MiR-375 suppression enhanced the ability of chondrocyte to antagonize the oxidative stress and maintained the homeostasis of extracellular matrix metabolism to protect chondrocytes from OA via activation of the JAK2/STAT3 pathway, indicating that miR-375 is a potential molecular target for OA treatment. © 2020 S. Karger AG, Basel.In this article, we use a case to illustrate and discuss some practically important learning points about programming subthalamic nucleus deep brain stimulation for Parkinson's disease patients and highlight clinically relevant issues resulting from anatomical and device-related anomalies. These include the phenomenon of a dominant subthalamic nucleus, clinical variability with delayed response to stimulation, equivalence of electrical charge when using short-pulse settings, and issues regarding conversion of settings between constant-current and constant-voltage devices that are increasingly common with the use of device components from multiple manufacturers. © 2020 S. Karger AG, Basel.OBJECTIVE The purpose of the present study was to determine the fraction of patients with mixed hearing loss who can or cannot expect benefit from power hearing aids (HAs) after stapes surgery. DESIGN The audiological outcome of 374 stapes surgeries was used to calculate the patients' individual postoperative requirements in terms of gain and output of HAs. These requirements were compared to the available gain and output provided by state-of-the-art power HAs at 0.5, 1.0, 2.0, and 4.0 kHz. According to these comparisons, ears were divided into three groups. For G0, required gain and output lay within the corresponding technical limits of the HAs at all frequencies. In G1, one or both requirements could not be fulfilled at 1 frequency. G2 combined all ears where the requirements lay beyond the HA's technical limitations at 2 or more frequencies. RESULTS Stapes surgery resulted in an improvement of air-bone gap (ABG) in 84.5% of the cases by 15.7 dB on average. Based on pure-tone average (0.5, 1.0, 2.0, 4.0 kHz), 40.6% of all cases showed an ABG ≤10 dB. 44.9% of all cases did no longer need a HA after stapes surgery. A power HA would fulfill both audiological criteria at all 4 frequencies in 81.6% of cases that needed a HA postoperatively. However, 18.4% would not be sufficiently treatable at 1 or more frequencies (15.0% in G1, 3.4% in G2). CONCLUSIONS The present study identified a subset of patients with mixed hearing loss after stapes surgery that cannot be treated sufficiently with available power HAs. As the residual ABG is an important reason for this lack of treatment success, the advancement of alternative hearing devices that circumvent the middle ear, such as powerful active middle ear implants, is indicated. © 2020 S. Karger AG, Basel.INTRODUCTION Neuroglial functions may be deteriorated in major depressive disorder (MDD). OBJECTIVE To evaluate the markers of glial and neuronal cell turnover and to explore their associations with brain metabolites. METHODS In 10 participants with MDD and 10 healthy controls (HC) we investigated neuronal and glial plasma markers (the neuron-specific enolase, NSE; and S100beta, S100B) and brain metabolites (N-acetyl aspartate, NAA; total choline, Cho; and total creatine, Cr). Blood was collected for NSE and S100B. NAA, Cho, and Cr metabolite levels were measured in the anterior cingulate cortex (ACC) with proton magnetic resonance spectroscopy (1H-MRS) at 3T. RESULTS NSE and S100B levels were significantly higher in MDD subjects than in HC. The Cr level was significantly higher in MDD subjects than in HC, but the NAA and Cho levels did not differ between groups. NAA/Cr and Cho/Cr ratios were significantly lower in patients with MDD versus HC. S100B was negatively correlated with the Cho levels. CONCLUSIONS These results provide supporting evidence of neuronal and glial distress in MDD.
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