Efficacy of high dose systemic versus combined (systemic and intratympanic) corticosteroid therapy in idiopathic sudden sensorineural hearing loss: A prospective randomized trial and risk factor analysis.

The pathophysiology and the proper treatment of idiopathic sudden sensorineural hearing loss (ISSNHL) are an ongoing subject of debate. Locally or systemic administered corticosteroids are the most accepted drugs of treatment in reference to ISSNHL (idiopathic sudden sensorineural hearing loss), however, no strong evidence nor guidelines regarding their effectiveness yet exists. In our prospective, randomized, controlled trial 78 participants were enrolled. Patients were randomly assigned based on the day of admission to two groups according to treatment: group SS (n = 43) received intravenous systemic methylprednisolone alone, and group CT (n = 35) received intratympanic dexamethasone + systemic methylprednisolone. The primary outcome was to compare the hearing outcomes between the treatment groups based on different, widely accepted categories (Siegel, Kanzaki, modified Siegel and PTA4 gain). In consideration of the secondary outcome, we examined the effect of the various risk factors on the hearing improvement. No differences were detected regarding hearing improvement between the two groups, based on any criteria [Siegel's criteria (p = 0.604); Kanzaki's criteria (p = 0.720); modified Siegel's criteria (p = 0.524) and PTA 4 gain (p = 0.569)]. However, several clinical factors such as vertigo (p = 0.039), or cardiovascular comorbidity (p = 0.02) and the severity of initial hearing loss (p = 0.033) were found to bear a significant impact upon the hearing outcome. To the best of our knowledge, this is the first randomized controlled trial comparing high dose systemic and combination corticosteroid therapy in ISSNHL patients. Our findings suggest coexisting cardiovascular comorbidity, vertigo and severity of the initial hearing loss may bear a significantly higher impact upon hearing improvement, than the additional intratympanic steroid administration. The presented trial was registered in the European Union Drug Regulating Authorities Clinical Trials Database (name: Combinated systemic and intratympanic steroid therapy in idiopathic sudden sensorineural hearing loss, No.: 2017-000658-20) and with the ethical approval of The National Institute of Pharmacy and Nutrition (OGYÉI) (protocol No.: 7621, on 2017.02.16.).

Effect of malnutrition and body composition on the quality of life of COPD patients.

BACKGROUND: Pathological alterations in nutritional status may develop in Chronic Obstructive Pulmonary Disease (COPD) patients through production of inflammatory cytokines and inadequate diet. OBJECTIVE: The aim of our study was to determine the correlation between nutritional status and quality of life of COPD patients. METHODS: We evaluated the nutritional status of COPD patients of Hungarian National Koranyi Institute for Pulmonology using the Malnutrition Universal Screening Tool (MUST) and bioelectrical impedance analysis (BIA) between January 1 and June 1, 2019. Lung function, physical fitness, and respiratory muscle strength were included in the assessment. RESULTS: Fifty patients (mean age was 66.3 ± 9.6 years) participated in our study. Mean body mass index (BMI) was 26.2 ± 6.1 kg/m2 and mean fat-free mass index (FFMI) was 16.8 ± 2.4 kg/m2. Overweight patients had better lung function values (FEV1ref%: 46.3 ± 15.2) than normal (FEV1ref%: 45.1 ± 20.9) and underweight patients (FEV1ref%: 43.8 ± 16.0). The Modified Medical Research Council Dyspnea Scale (mMRC) was significantly associated with various parameters; strongest correlation was found with FFMI (r = -0.537, P < 0.001), skeletal muscle mass index (SMMI) (r = -0.530, P < 0.001), and 6-minute walking distance (6MWD) (r = -0.481, P < 0.001). CONCLUSIONS: Our results indicate that malnourished COPD patients may have reduced lung function and lower quality of life compared to normal weight patients. Thus, our findings suggest that nutritional therapy be included in the treatment of COPD patients combined with nutritional risk screening and BIA during the follow-up.

[COVID-19 and the central and peripheral nervous system]. / COVID-19: Auswirkungen auf das zentrale und periphere Nervensystem.

The health effects of coronavirus disease 2019 (COVID-19) caused by the infection of SARS-CoV­2 (severe acute respiratory syndrome coronavirus 2) are becoming increasingly clear as the pandemic spreads. In addition to the lungs, other organs are also affected, which can significantly influence morbidity and mortality. In particular, neurological symptoms involving the central nervous system can lead to acute or long-term consequences. The mechanisms of this neuropathogenesis of SARS-CoV­2 infection and its relation to acute and chronic neurological symptoms are the subject of current studies investigating a potential direct and indirect viral infection of the nervous system. The following review summarizes the current status of neuropathological manifestations, molecular pathogenesis, possible infection pathways in the nervous system, and systemic effects. In addition, an overview of the Germany-wide CNS-COVID19 registry and collaborations is presented, which should contribute to a better understanding of the neurological symptoms of COVID-19.

A clinical diagnostic algorithm for early onset cerebellar ataxia.

Early onset cerebellar Ataxia (EOAc) comprises a large group of rare heterogeneous disorders. Determination of the underlying etiology can be difficult given the broad differential diagnosis and the complexity of the genotype-phenotype relationships. This may change the diagnostic work-up into a time-consuming, costly and not always rewarding task. In this overview, the Childhood Ataxia and Cerebellar Group of the European Pediatric Neurology Society (CACG-EPNS) presents a diagnostic algorithm for EOAc patients. In seven consecutive steps, the algorithm leads the clinician through the diagnostic process, including EOA identification, application of the Inventory of Non-Ataxic Signs (INAS), consideration of the family history, neuro-imaging, laboratory investigations, genetic testing by array CGH and Next Generation Sequencing (NGS). In children with EOAc, this algorithm is intended to contribute to the diagnostic process and to allow uniform data entry in EOAc databases.

A Practical Review of Functional MRI Anatomy of the Language and Motor Systems.

Functional MR imaging is being performed with increasing frequency in the typical neuroradiology practice; however, many readers of these studies have only a limited knowledge of the functional anatomy of the brain. This text will delineate the locations, anatomic boundaries, and functions of the cortical regions of the brain most commonly encountered in clinical practice-specifically, the regions involved in movement and language.

Flow cytometric analysis of extracellular vesicle subsets in plasma: impact of swarm by particles of non-interest.

Essentials Extracellular vesicles (EVs) in biological fluids are promising biomarkers for disease. Fluorescence-based flow cytometric analysis is suitable to detect low abundant EV subsets. Particles of non-interest can induce false-positive light scatter and fluorescent signals. Interference of particles of non-interest can be monitored by analyzing serial dilutions. SUMMARY: Background Extracellular vesicles (EVs) in plasma are increasingly being recognized as potential biomarkers. EV analysis for diagnostic purposes should be robust and should allow analysis of EV subsets with a wide range of abundance and in a large number of patient samples. Flow cytometry offers possibilities to meet these criteria, as it allows multiparameter analysis of individual EVs. However, analysis of plasma EVs is challenging, because of their size and heterogeneity, and the presence of other submicrometer-sized particles in plasma that could interfere with EV analysis. Objectives To explore whether fluorescence-based flow cytometric analysis of EV subsets is suitable when the EVs of interest are present in low abundance in a background of non-labeled or differently labeled EVs and particles. Methods Fluorescently labeled EVs of interest were spiked at different ratios in full plasma, purified plasma components, or (non-)fluorescent polystyrene beads, and subsequently analyzed by flow cytometry with fluorescence threshold triggering. Results We found that light scatter detection of low-abundance or rare EV subsets during fluorescence threshold triggering was severely affected by particles of non-interest, owing to coincidence and swarming. Importantly, we show that interfering particles labeled with different fluorophores induced false-positive fluorescent signals on the particles of interest. These unwanted effects could only be discerned and controlled by performing serial dilutions and analyzing light scatter and fluorescence parameters. Conclusions We demonstrate how particles of non-interest in plasma can impact on the light scatter and fluorescence detection of low-abundance EVs of interest during fluorescence-based flow cytometric analysis, and provide a means to prevent erroneous data interpretation.

Alterations in the metabolic and cardiorespiratory response to exercise in Huntington's Disease.

BACKGROUND: Limited data suggests that an altered metabolic and cardiorespiratory exercise response may affect exercise performance in individuals with Huntington's disease (HD). There is no clear exploration of the response in individuals at different stages of the disease or in relation to genetic markers. This study aimed to examine the exercise response and recovery of HD participants, and the relationship to genetic and clinical markers. METHOD: HD gene-positive participants (n = 31; 9 pre-manifest; 22 manifest HD) and a healthy control group (n = 29) performed an incremental exercise test until exhaustion. Performance, cardiorespiratory, metabolic and perceptual responses to exercise were determined from a maximal cycle ergometer test throughout the exercise test and during a recovery period. RESULTS: During sub-maximal exercise, metabolic (lactate levels, oxygen uptake) and cardiorespiratory markers (heart rate) were elevated in HD participants compared to controls. Lactate elevation was specific to pre-manifest HD participants. Work capacity was reduced in both pre-manifest and manifest HD participants with tests terminated with no difference in metabolic, perceptual or cardiorespiratory markers. Submaximal oxygen uptake was correlated with motor score, whilst peak measures were unrelated to genetic or clinical markers. Heart rate recovery was attenuated in pre-manifest and manifest HD participants. CONCLUSIONS: Our findings confirm metabolic and cardiorespiratory deficits reduce exercise performance and affect recovery from an early stage in HD, with submaximal deficits related to phenotypic expression. Exercise capacity appears to be limited by an altered movement economy, thus clinicians should consider an altered exercise response and recovery may affect prescription in HD.

Corrosion Resistance of Nanosized Silicon Carbide-Rich Composite Coatings Produced by Noble Gas Ion Mixing.

Ion beam mixing has been used to produce a silicon carbide (SiC)-rich nanolayer for protective coating. Different C/Si/C/Si/C/Si(substrate) multilayer structures (with individual layer thicknesses falling in the range of 10-20 nm) have been irradiated by Ar+ and Xe+ ions at room temperature in the energy and fluence ranges of 40-120 keV and 1-6 × 1016 ion/cm2, respectively. The effects of ion irradiation, including the in-depth distribution of the SiC produced, was determined by Auger electron spectroscopy depth profiling. The thickness of the SiC-rich region was only some nanometers, and it could be tailored by changing the layer structure and the ion irradiation conditions. The corrosion resistance of the layers was investigated by potentiodynamic electrochemical test in 4 M KOH solution. The measured corrosion resistance of the SiC-rich layers was orders of magnitude better than that of pure silicon, and a correlation was found between the corrosion current density and the effective areal density of the SiC.

Pacemakers in MRI for the Neuroradiologist.

Cardiac implantable electronic devices are frequently encountered in clinical practice in patients being screened for MR imaging examinations. Traditionally, the presence of these devices has been considered a contraindication to undergoing MR imaging. Growing evidence suggests that most of these patients can safely undergo an MR imaging examination if certain conditions are met. This document will review the relevant cardiac implantable electronic devices encountered in practice today, the background physics/technical factors related to scanning these devices, the multidisciplinary screening protocol used at our institution for scanning patients with implantable cardiac devices, and our experience in safely performing these examinations since 2010.

Monocyte activation drives preservation of membrane thiols by promoting release of oxidised membrane moieties via extracellular vesicles.

The redox state of cellular exofacial molecules is reflected by the amount of available thiols. Furthermore, surface thiols can be considered as indicators of immune cell activation. One group of thiol containing proteins, peroxiredoxins, in particular, have been associated with inflammation. In this study, we assessed surface thiols of the U937 and Thp1 monocyte cell lines and primary monocytes in vitro upon inflammatory stimulation by irreversibly labelling the cells with a fluorescent derivative of maleimide. We also investigated exofacial thiols on circulating blood mononuclear cells in patients with rheumatoid arthritis and healthy controls. When analysing extracellular vesicles, we combined thiol labelling with the use of antibodies to specific CD markers to exclude extracellular vesicle mimicking signals from thiol containing protein aggregates. Furthermore, differential detergent lysis was applied to confirm the vesicular nature of the detected extracellular events in blood plasma. We found an increase in exofacial thiols on monocytes upon in vitro stimulation by LPS or TNF, both in primary monocytes and monocytic cell lines (p<0.0005). At the same time, newly released extracellular vesicles showed a decrease in their exofacial thiols compared with those from unstimulated cells (p<0.05). We also found a significant elevation of surface thiols on circulating monocytes in rheumatoid arthritis patients (p<0.05) and newly released extracellular vesicles of isolated CD14+ cells from rheumatoid arthritis patients had decreased thiol levels compared with healthy subjects (p<0.01). Exofacial peroxiredoxin 1 was demonstrated on the surface of primary and cultured monocytes, and the number of peroxiredoxin 1 positive extracellular vesicles was increased in rheumatoid arthritis blood plasma (p<0.05). Furthermore, an overoxidised form of peroxiredoxin was detected in extracellular vesicle-enriched preparations from blood plasma. Our data show that cell surface thiols play a protective role and reflect oxidative stress resistance state in activated immune cells. Furthermore, they support a role of extracellular vesicles in the redox regulation of human monocytes, possibly representing an antioxidant mechanism.

Impaired intention-to-treat survival after listing for liver transplantation in children with biliary atresia compared to other chronic liver diseases: 20 years' experience from the Nordic countries.

Biliary atresia (BA) is the most common indication for LT in children. We investigated whether this diagnosis per se, compared to other chronic liver diseases (OCLD), had an influence on patient survival. Data from 421 Scandinavian children, 194 with BA and 227 with OCLD, listed for LT between 1990 and 2010 were analyzed. The intention-to-treat survival and influencing risk factors were studied. Patients with BA had higher risk of death after listing than patients with OCLD. The youngest (<1 year) and smallest (<10 kg) children with the highest bilirubin (>510 µmol/L), highest INR (>1.6), and highest PELD score (>20) listed during 1990s had the worst outcome. Given the same PELD score, patients with BA had higher risk of death than patients with OCLD. For adolescents, low weight/BMI was the only prognostic marker. Impaired intention-to-treat survival in patients with BA was mainly explained by more advanced liver disease in younger ages and higher proportion of young children in the BA group rather than diagnosis per se. PELD score predicted death, but seemed to underestimate the severity of liver disease in patients with BA. Poor nutritional status and severe cholestasis had negative impact on survival, supporting the "sickest children first" allocation policy and correction of malnutrition before surgery.

Fast, sensitive point of care electrochemical molecular system for point mutation and select agent detection.

Point of care molecular diagnostics benefits from a portable battery-operated device capable of performing a fast turnaround using reliable inexpensive cartridges. We describe a prototype device for performing a molecular diagnostics test for clinical and biodefense samples in 16 minutes using a prototype capable of an 8 minute PCR reaction, followed by hybridization and detection on an electrochemical microarray based on the i-STAT® system. We used human buccal swabs for hemochromatosis testing including in-device DNA extraction. Additional clinical and biodefense samples included influenza A and bacterial select agents Bacillus anthracis, Yersinia pestis and Francisella tularensis.

Neuropsychological Development in Patients with Long-Chain 3-Hydroxyacyl-CoA Dehydrogenase (LCHAD) Deficiency.

BACKGROUND: Reports on cognitive outcomes in long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency (LCHADD) are scarce. We present results from neuropsychological assessments of eight patients diagnosed with LCHADD prior to newborn screening with regard to clinical disease severity. METHODS: Intellectual ability and adaptive and executive functions were assessed using age-appropriate Wechsler Scales, Adaptive Behavior Assessment Scales (ABAS), and Behavior Rating Inventory of Executive Function (BRIEF). RESULTS: Five patients performed in the normal range on IQ tests but with lower scores on verbal working memory. In addition, they had lower parent-rated adaptive and executive functions.Three patients had intellectual disabilities with IQs below normal and/or autism spectrum disorders. In addition, they had low results on parent-rated adaptive functions. (Two of these patients had epilepsy.) Conclusions: Patients with LCHADD seem to have a specific cognitive pattern, with presentation as intellectual disability and specific autistic deficiencies or a normal IQ with weaknesses in auditive verbal memory and adaptive and executive functions. Future studies are warranted to investigate whether newborn screening programs and early treatment may promote improved neuropsychological development and outcomes.

De Novo Donor-Specific HLA Antibody Formation in Two Patients With Crigler-Najjar Syndrome Type I Following Human Hepatocyte Transplantation With Partial Hepatectomy Preconditioning.

Clinical hepatocyte transplantation is hampered by low engraftment rates and gradual loss of function resulting in incomplete correction of the underlying disease. Preconditioning with partial hepatectomy improves engraftment in animal studies. Our aim was to study safety and efficacy of partial hepatectomy preconditioning in clinical hepatocyte transplantation. Two patients with Crigler-Najjar syndrome type I underwent liver resection followed by hepatocyte transplantation. A transient increase of hepatocyte growth factor was seen, suggesting that this procedure provides a regenerative stimulus. Serum bilirubin was decreased by 50%, and presence of bilirubin glucuronides in bile confirmed graft function in both cases; however, graft function was lost due to discontinuation of immunosuppressive therapy in one patient. In the other patient, serum bilirubin gradually increased to pretransplant concentrations after ≈600 days. In both cases, loss of graft function was temporally associated with emergence of human leukocyte antigen donor-specific antibodies (DSAs). In conclusion, partial hepatectomy in combination with hepatocyte transplantation was safe and induced a robust release of hepatocyte growth factor, but its efficacy on hepatocyte engraftment needs to be evaluated with additional studies. To our knowledge, this study provides the first description of de novo DSAs after hepatocyte transplantation associated with graft loss.

Experimental study on the mechanical interaction between silicon neural microprobes and rat dura mater during insertion.

In vivo insertion experiments are essential to optimize novel neural implants. Our work focuses on the interaction between intact dura mater of rats and as-fabricated single-shaft silicon microprobes realized by deep reactive ion etching. Implantation parameters like penetration force and dimpling through intact dura mater were studied as a function of insertion speed, microprobe cross-section, tip angle and animal age. To reduce tissue resistance, we proposed a unique tip sharpening technique, which was also evaluated in in vivo insertion tests. By doubling the insertion speed (between 1.2 and 10.5 mm/min), an increase of 10-35% in penetration forces was measured. When decreasing the cross-section of the microprobes, penetration forces and dimpling was reduced by as much as 30-50% at constant insertion speeds. Force was noticed to gradually decrease by decreasing tip angles. Measured penetration forces through dura mater were reduced even down to 11±3 mN compared to unsharpened (49±13 mN) probes by utilizing our unique tip sharpening technique, which is very close to exerted penetration force in the case of retracted dura (5±1.5 mN). Our findings imply that age remarkably alters the elasticity of intact dura mater. The decreasing stiffness of dura mater results in a significant rise in penetration force and decrease in dimpling. Our work is the first in vivo comparative study on microelectrode penetration through intact and retracted dura mater.

Exercise testing and training in people with Huntington's disease.

OBJECTIVE: To explore exercise response in people with Huntington's disease (HD). DESIGN: Experimental observational study with a randomly allocated subgroup before/after interventional study. SETTING: Community. SUBJECTS: People with HD (n=30) and a healthy comparator group (n=20). Thirteen people from the HD group were randomly allocated to an exercise training program. MAIN MEASURES: Heart rate (HR) and perceived exertion on the Borg-CR10 scale (RPE) during a submaximal cycle ergometer exercise test (three minute unloaded and nine minute 65%-75%HRmaximum phase). Expired air and lactate measures were available for 8 people with HD during the exercise. INTERVENTION: A 12 week gym and home walking exercise programme (n=13). RESULTS: People with HD achieved a lower work rate at nine minutes (82±42(0-195) v 107±35(50 -185) Watts (p<0.05)), but higher RPE at both three (3±2(0-7) v 1±1(0-4)) and nine minutes (7±3(1-10) v 5± 2(2-9)) both p<0.01, compared to the healthy group and did not achieve a steady state HR during unloaded cycling. People with HD also demonstrated higher than expected lactate at three 2.5±2.5(1.1-8)mmo.L-1 and nine 3.8±1.9(1.2-6.6)mmo.L-1 minutes and respiratory exchange ratio at three 0.78±0.03 (0.74-0.81) and nine minutes 0.94±0.11(0.81-1.15). After exercise training there were no changes observed in HR or RPE responses during the exercise test. CONCLUSIONS: There was a large variability in the observed metabolic and physiological responses to exercise in people with HD. The observed exercise responses suggest that altered exercise prescription parameters may be required for people with HD and that exercise response and factors' affecting this requires further investigation.

Evaluation of the effect of Lake Hévíz thermal mineral water in patients with osteoarthritis of the knee: a randomized, controlled, single-blind, follow-up study.

BACKGROUND: Osteoarthritis is the most frequent joint disease and is a leading cause of pain and locomotor disability in elderly people. The treatment of osteoarthritis includes non-pharmacological, pharmacological, and surgical therapies. Silver level evidence has been found concerning balneotherapy in osteoarthritis. AIM OF THE STUDY: The aim of this study was to evaluate how Lake Hévíz thermal mineral water therapy influences pain, knee function, and quality of life in patients with knee osteoarthritis, compared to the control group. STUDY DESIGN: randomized, controlled, single-blind, follow-up study. SETTING: Spa Hévíz and St. Andrew Hospital for Rheumatic Diseases POPULATION: This study included 77 outpatients between 45 and 75 years of age with mild to moderate osteoarthritis of the knee meeting the American College of Rheumatology classification criteria. METHODS: Patients were randomized into two groups. In group I (n = 38), subjects bathed in Lake Hévíz and in group II (N.=39), patients were treated in a pool full of tap water. Water temperature was 34 °C for both groups. Participants underwent 30-minute therapy sessions, five times a week for three weeks. Outcome measures were pain visual analogue scale scores, active flexion degree, knee circumference, stair-climb time, Western Ontario and McMaster Universities osteoarthritis index (WOMAC), and EuroQoL Group 5-Dimension Self-Report Questionnaire score (EQ-5D). Study parameters were recorded at baseline, immediately after treatment, and after 15 weeks. RESULTS: Comparison of the two groups revealed a statistically significant difference in pain visual analogue scale scores (P<0.01), active flexion degree (P<0.01), physical function components of WOMAC (P<0.05), and EQ-5D scores (P<0.05) even after 15 weeks. CONCLUSIONS: Balneotherapy improved pain, function as well as the quality of life in patients with knee osteoarthritis. CLINICAL REHABILITATION IMPACT: Balneotherapy is a potentially useful treatment modality for patients with knee osteoarthritis.