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Background: Seismocardiography (SCG) is a useful method for the detection of exercise-induced changes in cardiac muscle contractility which may occur during myocardial ischemia. The aim of this study was to compare the diagnostic accuracy of SCG with electrocardiographic exercise test (ETT) for diagnosis of ischemia in patients with angiographically proved coronary artery disease (CAD).Methods: Seventy-seven male patients with CAD without myocardial infarction (MI), mean age 51+/-9 years, were subjected to SCG and ETT. A gender-matched control group consisted of 30 healthy volunteers aged 34+/-7 years. SCG was done simultaneously with resting supine 12-lead electrocardiography before and immediately after a symptom-limited ETT. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) of SCG were compared with ETT. Moreover, the diagnostic accuracy of both the methods was compared, with coronary angiography being the reference for the analysis.Results: SCG was more sensitive (61.1% vs 44.2%, P<0.05) and accurate (70% vs 61%, P<0.05) method for detecting ischemia caused by coronary stenosis>or=50%, at least in one coronary artery compared to the ETT. However, ETT had better specificity than SCG (82.4% vs 76%, P<0.05). The PPV and NPV of SCG were significantly better than those obtained with ETT (77.9% vs 76%, P<0.05 and 63.4% vs 53.8%, P<0.05, respectively). Moreover, the concordant results of SCG and ETT improved the diagnostic accuracy of both methods.Conclusions: SCG appeared to be more sensitive for detecting ischemia caused by more than>or=50% stenosis of the main coronary artery compared to an electrocardiographic stress test. SCG was a useful ETT adjunct for selecting patients requiring coronary angiography. [ABSTRACT FROM AUTHOR]

Abstract Introduction Staphylococcus aureus infection, and health care-associated-methicillin resistant S aureus (HA-MRSA) in particular, is a serious risk for patients treated with organ transplantation. The frequent combined resistance of these bacteria to macrolides, lincosamides, and streptogramin-B (MLS-B) limits the use of these drugs in therapy. Aim Evaluation of the mechanism of MLS-B resistance among HA-MRSA strains derived from patients treated in surgical-transplantation wards, over a 24-year period, and assessment of correlation of clindamycin use and resistance phenotype. Materials and methods One hundred and twelve HA-MRSA strains from patients in surgical-transplantation wards (clinical hospital, Warsaw), hospitalized in the period from 1991 to 2014. Methicillin-resistance was determined using phenotypic and genetic methods by detecting the mecA gene. Erythromycin/clindamycin resistance was determined by E-test, the iMLS-B (inductive) and cMLS-B (constitutive) phenotypes by the D-test method. The number of defined daily doses (DDD), statistically per 1000 person-days, was calculated in accordance with the WHO guidelines. Results Resistance to erythromycin/clindamycin in MRSA strains increased from 1991 to 2004–2007 from 64.7/11.8% to 100/76.9%, respectively. The frequency of the cMLS-B phenotype in the years 1991/2010–2011/2012 was 5.9%/76.9%/69.7%, respectively, and correlated with the increased use of clindamycin in the examined wards. In 2012, the percentage of MLS-B-sensitive isolates increased from 3.9 to 21.7%, while constitutive resistance decreased to 69.7%, which correlated with a decrease in the use of clindamycin. Conclusions The proportion of cMLS-B to iMLS-B phenotypes in HA-MRSA is related to the amount of clindamycin used in hospital wards. Limiting the selection pressure of antibiotics can lead to complete loss of resistance or return to the inductive mechanism of its regulation. Highlights • cMLS-B MRSA were selected under the pressure of clindamycin from previous iMLS-B. • Spontaneous mutations caused an increase in the incidence of cMLS-B variants. • A 14-fold increase in the occurrence of cMLS-B was noted between 1991 and 2014. • Limiting clindamycin use may lead to restoration of the inducible phenotype. [ABSTRACT FROM AUTHOR]

Introduction: Atrial fibrillation (AF) is the most common sustained arrhythmia, and catheter ablation (CA) is a primary therapeutic option. However, the 30-day all-cause mortality risk associated with CA for AF may be underestimated due to selection bias. Our study aimed to assess 30-day mortality in an unselected cohort of patients., Methods: Data from the National Health Fund-Poland covered over 99% of nationwide radiofrequency ablation (RF) or cryoballoon ablation for AF, with 100% recorded deaths. The study included consecutive CA procedures in adult patients between 2012 and 2019. Thirty-day mortality rates were calculated for each age group., Results: A total of 31 214 CAs for AF were performed on 26 767 patients (34.8% female). Forty-four percent of patients had hypertension, 31.2% had coronary artery disease, 14.4% had heart failure, 11% had diabetes mellitus, 5.6% had malignant neoplasms, 2.7% had a previous myocardial infarction, 2.5% had a previous stroke, and 2.2% had kidney disease. Thirty-two deaths (0.1%) occurred within 30 days, with the highest mortality in the oldest age group (>80 years). Statistical analysis revealed higher incidences of kidney disease (p < 0.001) and heart failure (p = 0.001) in patients who died within 30 days. Mortality risk did not significantly differ between cryoballoon and RF ablation, as well as first and subsequent ablation for AF. The risk of death within 7 days postablation for AF was 1 in 2750 procedures, while the risk of death on the same day postablation was 1 in 6250 procedures., Conclusions: The 30-day mortality rate in a large, unselected AF ablation cohort, covering 99% of procedures in the country, is low except for the oldest patients. This factor should be taken into consideration when offering CA for AF., (© 2024 Wiley Periodicals LLC.)

Aim: To evaluate the presence and status of retained DM2 without permanent successors in relation to age., Background: Preservation of retained deciduous second molars (DM2) can be applied to treat congenital absence of second premolars (PM2). However, the consequences of caries and progressing root resorption or infraocclusion may affect their survival., Methods: Panoramic radiographs of individuals >10 years of age with agenesis of at least one PM2 were evaluated and divided into three groups according to age. The presence and location of retained DM2, caries/restorations, infraocclusion and root resorption were investigated., Results: A total of 131 subjects with PM2 agenesis were included (mean age: 13 years 11 months). The majority were missing one or two PM2. In total, 174 retained DM2 were present (33%), and their incidence was higher in the younger age groups. Caries/restorations were found in 88 (50.6%) and infraocclusion in 21 (12%) retained DM2. The roots were resorbed mostly for ½ of the root length (35%)., Conclusion: Long-term prognosis of retained DM2 without permanent successors seems uncertain, especially within the younger age group. In individuals older than 17 years, the prognosis for a healthy DM2 is favorable, if no distinct infraocclusion or extensive root resorption is present.

Background: The disturbed metabolism of ceramide (Cer) is supposed to evoke the autoimmune response, contributing to MS pathology., Objectives: To determine levels of anti-Cer immunoglobulins G (IgGs) in the CSF and serum of subjects with various phenotypes of MS, and to investigate relationships between levels of anti-Cer antibodies and MS-related variables., Methods: IgGs isolated from serum and the CSF of 68 MS patients and appropriate controls were examined for their reactivity to Cer subspecies. Their levels were compared between the studied groups and compartments, and analyzed with regard to clinical variables., Results: Increased levels of anti-C16:0-, C18:0-, C18:1-, C24:0- and C24:1-Cer IgGs were detected in the CSF and serum of MS patients in comparison with controls. For IgGs against particular Cer subspecies, correlations were found between their CSF and serum level, as well as with the Link index. Serum and the CSF anti-Cer IgGs differed between patients with clinically isolated syndrome (CIS) and relapsing-remitting MS from those with progressive MS. No correlations were found between anti-Cer IgGs and other MS-related clinical variables., Conclusion: Patients with MS have shown altered panels of anti-Cer IgGs in the CSF and serum, which might suggest a relevant, though limited role of Cer as a target for autoimmune humoral response. Utility of antibodies against Cer subspecies as potential markers for MS activity and progression deserves further investigations., Competing Interests: Declaration of Competing Interest The authors have no conflicting financial interests., (Copyright © 2023. Published by Elsevier B.V.)

This review aims to discuss and illustrate various uses of cantilevers to solve multiple clinical issues and prove their versatility. Cantilevers are commonly used in the segmented arch technique, and they can be designed to solve various clinical problems with highly predictable results. Its design and shape can modify the various combinations of vertical and horizontal forces. The novel trend is to combine cantilevers with skeletal anchorage. Cantilevers offer a very simple and statically determined force system. The advantage is the control over side effects, which normally occur on the anchor teeth and the occlusion. The disadvantages include possible side effects on the anchorage unit, when the anchorage is poorly controlled. The review highlights the clear benefits of cantilever use in complex corrections of single teeth, segments, and entire arch with a diminished effect on the dentition, also with the use of skeletal anchorage. With their simple and easily tailored design, these springs can be called an orthodontic multi-tool.

Intrusion with a three-piece arch is routinely achieved during orthodontic treatment. This study aimed to experimentally determine how the cantilever design influences the generated force system. Both straight and arch-formed cantilever designs: tip-back (TB), flat curve (FC) deep curve (DC), and 3 mm and 6 mm high utility arch (UA3; UA6) were activated for 5 mm and 10 mm. Force systems were determined by a hexapod. Typodonts simulating a three piece-intrusion arch were scanned using an intraoral scanner (3Shape, TRIOS, Denmark) before (T0) and after (T1) the experiment and superimposed with Mimics software (Materialise, Leuven, Belgium). Data were analyzed. All straight designs displayed an extrusive force in the vertical plane, and all arch-formed an intrusive force. DC and TB showed a retrusive force in the sagittal plane and UA6 a protrusive. For the medial/lateral forces, DC and TB displayed a medial, and UA6 a lateral force. Configurations can be distinctively ranked from DC, FC, TB to UA3, and UA6 according to the increasing protrusive nature of the generated sagittal forces. A DC or TB configuration should be used for intrusion and retraction, while for an intrusion and a protrusion, a UA6 configuration. All straight configurations showed a higher force level than the arch-formed configurations.

Cantilevers generate statically determined force systems. The frontal segment loading with symmetric and asymmetric cantilevers in a three-piece intrusion base arch can be used to correct midline asymmetry. Three types of 0.017″ × 0.025″ beta-titanium cantilevers: tip-back (TB), deep curve (DC), utility arch (UA) were tested on typodonts simulating intrusion of the maxillary anterior segment. Typodonts with symmetric and asymmetric cantilevers were scanned with intraoral scanner (3Shape, TRIOS, Copenhagen, Denmark) before (T0) and after (T1) the experiment, scans were superimposed using Mimics software (Materialise, Leuven, Belgium). Data were analysed with qualitative analysis. All cantilevers generated vertical and horizontal forces. For symmetric design, the DC and TB displayed intrusive force with retrusive component, UA intrusion and protrusion. The asymmetric cantilevers produced transverse displacement of anterior segment. DC created lateral, UA medial force, the anterior segment displacement was consistent with the used configuration. The movement of an anterior segment with TB is smaller compared to DC and UA. Symmetric cantilevers configurations can achieve simultaneous intrusion and retrusion or protrusion of the anterior segment. The asymmetric design with transversal force can clinically aid the correction of midline discrepancies. The effect of the cantilever configuration on delivered force direction was confirmed.

Background: There is an unmet need for treatment options for generalised myasthenia gravis that are effective, targeted, well tolerated, and can be used in a broad population of patients. We aimed to assess the safety and efficacy of efgartigimod (ARGX-113), a human IgG1 antibody Fc fragment engineered to reduce pathogenic IgG autoantibody levels, in patients with generalised myasthenia gravis., Methods: ADAPT was a randomised, double-blind, placebo-controlled, phase 3 trial done at 56 neuromuscular academic and community centres in 15 countries in North America, Europe, and Japan. Patients aged at least 18 years with generalised myasthenia gravis were eligible to participate in the study, regardless of anti-acetylcholine receptor antibody status, if they had a Myasthenia Gravis Activities of Daily Living (MG-ADL) score of at least 5 (>50% non-ocular), and were on a stable dose of at least one treatment for generalised myasthenia gravis. Patients were randomly assigned by interactive response technology (1:1) to efgartigimod (10 mg/kg) or matching placebo, administered as four infusions per cycle (one infusion per week), repeated as needed depending on clinical response no sooner than 8 weeks after initiation of the previous cycle. Patients, investigators, and clinical site staff were all masked to treatment allocation. The primary endpoint was proportion of acetylcholine receptor antibody-positive patients who were MG-ADL responders (≥2-point MG-ADL improvement sustained for ≥4 weeks) in the first treatment cycle. The primary analysis was done in the modified intention-to-treat population of all acetylcholine receptor antibody-positive patients who had a valid baseline MG-ADL assessment and at least one post-baseline MG-ADL assessment. The safety analysis included all randomly assigned patients who received at least one dose or part dose of efgartigimod or placebo. This trial is registered at ClinicalTrials.gov (NCT03669588); an open-label extension is ongoing (ADAPT+, NCT03770403)., Findings: Between Sept 5, 2018, and Nov 26, 2019, 167 patients (84 in the efgartigimod group and 83 in the placebo group) were enrolled, randomly assigned, and treated. 129 (77%) were acetylcholine receptor antibody-positive. Of these patients, more of those in the efgartigimod group were MG-ADL responders (44 [68%] of 65) in cycle 1 than in the placebo group (19 [30%] of 64), with an odds ratio of 4·95 (95% CI 2·21-11·53, p<0·0001). 65 (77%) of 84 patients in the efgartigimod group and 70 (84%) of 83 in the placebo group had treatment-emergent adverse events, with the most frequent being headache (efgartigimod 24 [29%] vs placebo 23 [28%]) and nasopharyngitis (efgartigimod ten [12%] vs placebo 15 [18%]). Four (5%) efgartigimod-treated patients and seven (8%) patients in the placebo group had a serious adverse event. Three patients in each treatment group (4%) discontinued treatment during the study. There were no deaths., Interpretation: Efgartigimod was well tolerated and efficacious in patients with generalised myasthenia gravis. The individualised dosing based on clinical response was a unique feature of ADAPT, and translation to clinical practice with longer term safety and efficacy data will be further informed by the ongoing open-label extension., Funding: argenx., Competing Interests: Declaration of interests JFH has received research support from Alexion Pharmaceuticals, argenx, the Centers for Disease Control and Prevention (Atlanta, GA, USA), the Muscular Dystrophy Association, the National Institutes of Health (NIH; including the National Institute of Neurological Disorders and Stroke and the National Institute of Arthritis and Musculoskeletal and Skin Diseases), Patient Centered Outcomes Research Institute, and Ra Pharmaceuticals (now UCB); honoraria from Alexion Pharmaceuticals, argenx, Immunovant, Ra Pharmaceuticals (now UCB), Regeneron Pharmaceuticals, and Viela Bio; and non-financial support from Alexion Pharmaceuticals, argenx, Ra Pharmaceuticals (now UCB), and Toleranzia. VB has received research support from Commonwealth Serum Laboratories, Grifols, UCB, Bionevia, Shire, and Octapharma. TVu has served as a speaker for Alexion; has done consulting work for argenx and UCB; and participated in trials in myasthenia gravis sponsored by NIH, Alexion Pharmaceuticals, argenx, Ra, Viela Bio, UCB, and Grifols. CK has served on advisory boards for Acceleron, Akcea, Alexion, Alnylam, argenx, Biogen, CSL Behring, Cytokinetics, and Sanofi-Genzyme; and received research grants from Genzyme and Akcea. SP reports lecture honoraria from Pfizer, Teva Actavis, Berlin Chemie Menarini, Mylan, Worwag, Adoc, and Salveo; research grants from Kedrion, Octapharma, and Argenx; consultant fees from argenx, Mylan, and Roche; and travel grants from Octapharma, Kedrion, Teva Actavis, Sanofi Genzyme, Pfizer, Roche, Adoc, and Berlin Chemie Menarini, all outside the submitted work. HM has served as a paid consultant for Alexion Pharmaceuticals, argenx, and Ra Pharma; and has received speaker honoraria from the Japan Blood Products Organization and research support from the Ministry of Health, Labor, and Welfare, Japan. AG, PU, and TVa are full-time employees of argenx, Ghent, Belgium. KU has served as a paid consultant for argenx, Ra Pharma, UCB Pharma, Viela Bio, and Regeneron Pharmaceuticals; and has received speaker honoraria from Alexion Pharmaceuticals and the Japan Blood Products Organization. JV receives research support from Target to B consortium, Prinses Beatrix Spierfonds, and argenx; has been involved in trials or consultancies for argenx, Alexion, and Ra pharma; JV is coinventor on patent applications based on MUSK-related research; and is a member of the European Reference Network for Rare Neuromuscular Diseases; and JV's institution received royalties from Immuno-Biological Laboratories. RM has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with BioMarin, Catalyst, Alexion Pharmaceuticals, UCB, and argenx. All other authors declare no competing interests., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Multiple sclerosis (MS) is a CNS disease characterized by immune-mediated demyelination and progressive axonal loss. MS-related CNS damage and its clinical course have two main phases: active and inactive/progressive. Reliable biomarkers are being sought to allow identification of MS pathomechanisms and prediction of its course. The purpose of this study was to identify sphingolipid (SL) species as candidate biomarkers of inflammatory and neurodegenerative processes underlying MS pathology. We performed sphingolipidomic analysis by HPLC-tandem mass spectrometry to determine the lipid profiles in post mortem specimens from the normal-appearing white matter (NAWM) of the normal CNS (nCNS) from subjects with chronic MS (active and inactive lesions) as well as from patients with other neurological diseases. Distinctive SL modification patterns occurred in specimens from MS patients with chronic inactive plaques with respect to NAWM from the nCNS and active MS (Ac-MS) lesions. Chronic inactive MS (In-MS) lesions were characterized by decreased levels of dihydroceramide (dhCer), ceramide (Cer), and SM subspecies, whereas levels of hexosylceramide and Cer 1-phosphate (C1P) subspecies were significantly increased in comparison to NAWM of the nCNS as well as Ac-MS plaques. In contrast, Ac-MS lesions were characterized by a significant increase of major dhCer subspecies in comparison to NAWM of the nCNS. These results suggest the existence of different SL metabolic pathways in the active versus inactive phase within progressive stages of MS. Moreover, they suggest that C1P could be a new biomarker of the In-MS progressive phase, and its detection may help to develop future prognostic and therapeutic strategies for the disease., Competing Interests: Conflict of interest—The authors declare that they have no conflicts of interest with the contents of this article., (Copyright © 2020 Podbielska et al. Published by The American Society for Biochemistry and Molecular Biology, Inc.)

Mutations in the lamin A/C gene are variably phenotypically expressed; however, it is unclear whether circulating cardiac biomarkers are helpful in the detection and risk assessment of cardiolaminopathies. We sought to assess (1) clinical characteristics including serum biomarkers: high sensitivity troponin T (hsTnT) and N-terminal prohormone brain natriuretic peptide (NT-proBNP) in clinically stable cardiolaminopathy patients, and (2) outcome among pathogenic/likely pathogenic lamin A/C gene ( LMNA ) mutation carriers. Our single-centre cohort included 53 patients from 21 families. Clinical, laboratory, follow-up data were analysed. Median follow-up was 1522 days. The earliest abnormality, emerging in the second and third decades of life, was elevated hsTnT (in 12% and in 27% of patients, respectively), followed by the presence of atrioventricular block, heart failure, and malignant ventricular arrhythmia (MVA). In patients with missense vs. other mutations, we found no difference in MVA occurrence and, surprisingly, worse transplant-free survival. Increased levels of both hsTnT and NT-proBNP were strongly associated with MVA occurrence (HR > 13, p ≤ 0.02 in both) in univariable analysis. In multivariable analysis, NT-proBNP level > 150 pg/mL was the only independent indicator of MVA. We conclude that assessment of circulating cardiac biomarkers may help in the detection and risk assessment of cardiolaminopathies., Competing Interests: The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

The vast majority of cardiomyopathies have an autosomal dominant inheritance; hence, genetic testing is typically offered to patients with a positive family history. A de novo mutation is a new germline mutation not inherited from either parent. The purpose of our study was to search for de novo mutations in patients with cardiomyopathy and no evidence of the disease in the family. Using next-generation sequencing, we analyzed cardiomyopathy genes in 12 probands. In 8 (66.7%), we found de novo variants in known cardiomyopathy genes ( TTN , DSP , SCN5A , TNNC1 , TPM1 , CRYAB , MYH7 ). In the remaining probands, the analysis was extended to whole exome sequencing in a trio (proband and parents). We found de novo variants in genes that, so far, were not associated with any disease ( TRIB3 , SLC2A6 ), a possible disease-causing biallelic genotype ( APOBEC gene family), and a de novo mosaic variant without strong evidence of pathogenicity ( UNC45A ). The high prevalence of de novo mutations emphasizes that genetic screening is also indicated in cases of sporadic cardiomyopathy. Moreover, we have identified novel cardiomyopathy candidate genes that are likely to affect immunological function and/or reaction to stress that could be especially relevant in patients with disease onset associated with infection/infestation., Competing Interests: The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript or in the decision to publish the results.

Objective: To investigate safety and explore efficacy of efgartigimod (ARGX-113), an anti-neonatal Fc receptor immunoglobulin G1 Fc fragment, in patients with generalized myasthenia gravis (gMG) with a history of anti-acetylcholine receptor (AChR) autoantibodies, who were on stable standard-of-care myasthenia gravis (MG) treatment., Methods: A phase 2, exploratory, randomized, double-blind, placebo-controlled, 15-center study is described. Eligible patients were randomly assigned (1:1) to receive 4 doses over a 3-week period of either 10 mg/kg IV efgartigimod or matched placebo combined with their standard-of-care therapy. Primary endpoints were safety and tolerability. Secondary endpoints included efficacy (change from baseline to week 11 of Myasthenia Gravis Activities of Daily Living, Quantitative Myasthenia Gravis, and Myasthenia Gravis Composite disease severity scores, and of the revised 15-item Myasthenia Gravis Quality of Life scale), pharmacokinetics, pharmacodynamics, and immunogenicity., Results: Of the 35 screened patients, 24 were enrolled and randomized: 12 received efgartigimod and 12 placebo. Efgartigimod was well-tolerated in all patients, with no serious or severe adverse events reported, no relevant changes in vital signs or ECG findings observed, and no difference in adverse events between efgartigimod and placebo treatment. All patients treated with efgartigimod showed a rapid decrease in total immunoglobulin G (IgG) and anti-AChR autoantibody levels, and assessment using all 4 efficacy scales consistently demonstrated that 75% showed a rapid and long-lasting disease improvement., Conclusions: Efgartigimod was safe and well-tolerated. The correlation between reduction of levels of pathogenic IgG autoantibodies and disease improvement suggests that reducing pathogenic autoantibodies with efgartigimod may offer an innovative approach to treat MG., Classification of Evidence: This study provides Class I evidence that efgartigimod is safe and well-tolerated in patients with gMG., (© 2019 American Academy of Neurology.)

Multiple sclerosis (MS) is an inflammatory disease of the central nervous system (CNS), where inflammation, demyelination together with the axonopathy are the cardinal features on pathologic ground, with a combined genetic and environmental background. The associations of PD-1 single nucleotide polymorphisms (SNPs): PD-1.3 (in intron 4), PD-1.5 and PD-1.9 (both in exon 5) with clinical manifestation of MS in 479 south Polish individuals including 203 MS patients were analyzed. Presence of PD-1.5T allele was linked with the first manifestations of disease: diplopia and pyramidal signs - favored pyramidal signs but protected against of diplopia development. Farther, PD-1.3G/PD-1.5C/PD-1.9C haplotype significantly favored whereas GTC protected against diplopia. Besides, GTT haplotype strongly favored non-severe RRMS outcome and ATC haplotype was specific only for these MS patients. Our population-based case-control study, investigating selected three PD-1 SNPs: PD-1.3, PD-1.5 and PD-1.9, revealed that polymorphic variation may be rather disease-modifying than MS risk factor., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Objective: Cerebral lesion due to different neurological conditions could be complicated by autonomic dysfunction, reported in the literature as a sympathetic hyperactivity. The mechanisms of dysautonomia still remains partial. The aim of the study was to assess the profile of autonomic dysfunction in patient with primary brain tumors, with attempt to estimate the additional factors in pathogenesis of dysautonomia., Material and Methods: Neurological examinations, the Low's autonomic disorder questionnaire, electrophysiological autonomic tests (Heart Rate Variability test at rest and during deep breathing, spectral analysis of R-R intervals, sympathetic skin response test), studies of peripheral nerves, blood sampling collection for antibodies were done in 33 patients with recognized primary brain tumors., Results: The averaged Low's Questionnaire score in the patients group was significantly higher than in the controls, systolic blood pressure was increased, heart rate tended to be higher without significance, but heart rate variability was severe low, LF/HF ratio also tended to be higher in the patients group. In SSR test the amplitude of responses from hand and foot was significantly lower without changes in their latencies. We found changes in the electrophysiological tests of peripheral nerves, and positive anti-neural antibodies in 5 patients., Conclusions: The results of the study indicated to the sympathetic nervous system hyperactivity in patients with primary brain tumors. Local brain lesion with high intracranial pressure, additional peripheral nerve damage probably in the course of autoimmunity, and direct influence of autoimmunity to the central part of autonomic nervous system are possible in the pathogenesis of dysautonomia., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Objectives: Cognitive impairment and fatigue are regarded as important aspects of multiple sclerosis. The aim of this study was to evaluate cognitive performance, the level of fatigue and parameters of event-related potentials (ERP) in patients diagnosed with clinically isolated syndrome (CIS)., Patients and Methods: The study comprised 44 patients with CIS and 45 healthy controls. Cognitive performance was assessed using the Brief Repeatable Battery of Neuropsychological Tests (BRBNT), fatigue - using the Fatigue Severity Scale (FSS) and Modified Fatigue Impact Scale (MFIS). Auditory ERP were performed and the parameters of N200 and P300 components were analyzed. Neuropsychological and electrophysiological measures were referred to clinical and radiological features of the disease activity., Results: Forty five% of patients failed in at least one test from BRBNT, mainly within the domains of memory and attention. In 18% of patients FSS corresponded with moderate or severe fatigue. The mean latency of N200 and P300 was significantly longer and amplitude of P300 was lower in those patients with CIS than in the controls. Significant correlations were found between the results of MFIS and tests evaluating verbal memory and attention, as well as between N200 latency and results of tests for verbal memory., Conclusions: Cognitive performance and fatigue deserve attention from the earliest clinical stage of MS. Abnormalities of event-related potentials in CIS suggest early impact of the disease on functional neural networks., (Copyright © 2016 Elsevier B.V. All rights reserved.)

The aim of this study was to evaluate event-related potentials (ERP) and cognition in multiple sclerosis (MS) patients with regard to fatigue and disease-related variables. The study comprised 86 MS patients and 40 controls. Fatigue was assessed using the Fatigue Severity Scale (FSS/FSS-5) and the Modified Fatigue Impact Scale (MFIS/MFISmod). N200 and P300 components of auditory ERP were analyzed. Cognition was evaluated by means of Brief Repeatable Battery of Neuropsychological Tests (BRBNT). The results of ERP and BRBNT were compared between non-fatigued, moderately and severely fatigued MS patients and controls. P300 latency was significantly longer in the whole MS group and in the fatigued patients than in the controls. A positive correlation was found between P300 latency and MFIS/MFISmod results, independent from age and MS-related variables. The fatigued patients scored less than non-fatigued ones in tests evaluating memory, visuomotor abilities and attention. Results of these tests correlated significantly with fatigue measures, independently from MS-related variables. Fatigue in MS patients showed significant relationships with impairment within the memory and attention domains. Parameters of auditory ERP, as electrophysiological biomarkers of cognitive performance, were not independently linked to fatigue.

Introduction: Systemic malignant diseases cause the induction of autoimmunity, for example, paraneoplastic syndromes. There are no proofs of paraneoplastic syndromes in primary brain tumors. The aim of the study was to evaluate the involvement of the peripheral nervous system, together with an assessment of onconeuronal and antineural antibodies as indicators of humoral immune response against nervous system in patients with primary brain tumors., Materials and Methods: Clinical examinations, electrophysiological studies of peripheral nerves (motor and sensory conduction velocity studies, conduction velocity distribution tests, thermal and vibratory quantitative sensory tests, and sympathetic skin response tests) and muscles, blood sampling collection (assessment of onconeuronal, and antineural antibodies) were performed on 33 patients with newly recognized primary brain tumors within 2-4 days after their admission to our department., Results: We revealed statistically significant changes of peripheral nerves, more pronounced in the peroneal nerve in standard and conduction velocity distribution tests, as well as in sympathetic skin responses. We revealed significantly higher vibratory thresholds, and pain thresholds for cold and warm in the upper and lower limbs in the study group than in the controls. In five patients, we have identified anti-neuroendothelium, anti-GFAP, anti-MAG, anti-PCNA, and anti-Ro52 antibodies., Conclusions: In patients with primary brain tumors, electrophysiological changes in peripheral nerves, together with the presence of the antineural antibodies suggest an autoimmune humoral response, and make the diagnosis of paraneoplastic neurological syndrome possible.

The biological features of glioma cells may define their clinical outcome. Little is known about the interactions between KAI1/CD82 metastatic suppressor protein and PDGFR in gliomas. The aim of the study was to examine KAI1/CD82 and PDGFR expression in gliomas in order to find the impact of these proteins on progression of the tumors. PDGFR, KAI1/CD82 protein expression and mRNA of genes were evaluated on eighty four paraffin-embedded tissue of gliomas using immunohistochemical staining and RT-PCR analysis. The PDGFR expression was higher in IV/III than in I/II glioma grades (p = 0.0004). The level of mRNA PDGFR was associated with the degree of PDGFR immunoreactivity. Downregulation of KAI1/CD82 was associated with tumor malignancy (p = 0.007). The increased level of KAI1/CD82 gene expression (3-4-fold) was found in gliomas with strong KAI1/CD82 immunoreactivity. The parallel KAI1/CD82 and PDGFR expression was more significantly associated with cases in a group graded as III and IV than in a group graded as I/II (p = 0.002). We found that a loss of KAI1/CD82 and an increase in PDGFR expression in gliomas relate to a progressive tumor growth. The correlation between PDGFR and KAI1 expression in high grade gliomas suggests that a direct or indirect interaction between these proteins might have an impact on cell motility and invasive behavior of the tumor.

Eating disorders (ED) such as anorexia nervosa and bulimia are psychiatric diseases associated with the highest mortality rate of any other psychiatric disorders. More recently, long-term outcome studies with follow-up of over 20 years report a mortality of between 15% and 18% (Casiero and Frishman, Cardiol Rev 14(5), 227, 2006). The sudden death secondary to arrhythmias is often the cause of death in these patients (Casiero and Frishman, Cardiol Rev 14(5), 227, 2006). A case of life-threatening ventricular arrhythmia (VA) in a patient with ED is presented. Clinical records (cardiologic, psychiatric), electrocardiograms, echocardiogram, coronary angiogram, cardiac magnetic resonance, and endocrine diagnostics were performed. Finally a cardioverter-defibrillator (ICD) was implanted in the patient after her third cardiac arrest. An optimal approach to antiarrhythmic therapy in such patients is a real challenge for a cardiologist., (© 2014 Wiley Periodicals, Inc.)

The aim of the study was to evaluate visual and brainstem auditory evoked potentials (VEP, BAEP) in multiple sclerosis (MS) patients with regards to fatigue and disease-related variables. The study comprised 86 MS patients and 40 controls. Fatigue was assessed using the Fatigue Severity Scale (FSS/FSS-5) and the Modified Fatigue Impact Scale (MFIS). Latencies and amplitudes of the P100 component of VEP and the I-V components of BAEP were analyzed. The results of EP were compared between non-fatigued, moderately and severely fatigued MS patients and controls. P100 latency was increased and amplitude decreased in moderately and severely fatigued MS subjects. The latency of the V component of BAEP and interlatencies I-III-V were increased in severely fatigued patients. The amplitude of the V component was lowered in fatigued patients. VEP and BAEP abnormalities were usually one-sided. Interocular P100 latency difference tended to correlate with FSS/FSS-5. The parameters of VEP and BAEP correlated with functional system scores but not with MS duration, overall degree of disability or its progression over time. Significant, usually asymmetrical VEP and BAEP abnormalities were found in fatigued MS patients, with no relationships to disease-related variables. EP may be considered an electrophysiological marker of fatigue in MS patients.

Background: The origin of fatigue in multiple sclerosis (MS) remains unclear. Magnetic resonance spectroscopy (MRS) provides an insight into metabolic properties of the brain., Objectives: The aim of the study was to evaluate brain MRS measurements in MS patients, with regard to fatigue and cognition., Methods: The study comprised 32 MS patients and 43 controls. Fatigue was assessed using the Fatigue Severity Scale (FSS) and the Modified Fatigue Impact Scale (MFIS) and cognition - using the Brief Repeatable Battery of Neuropsychological Tests (parts of BRBNT). MRS voxels were placed in the parietal white matter (PWM) and the posterior cingulate gyrus (PCG); N-acetyl-aspartate (NAA), choline (Cho) and myoinositol (mI) to creatine (Cr) ratios were determined. Relationships were searched between MRS measurements and fatigue as well as BRBNT results., Results: MS patients in comparison with controls showed decreased NAA/Cr and increased mI/Cr ratios in PCG and PWM, respectively. No significant relationships between MRS parameters and fatigue measures, BRBNT results or MS-related variables were found., Conclusions: The decrease of NAA and increase of mI within white and gray matters in MS patients do not show a significant relationship with cognitive performance or fatigue., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Objective and Design: Peripheral neuropathy is a devastating uremic complication that causes debilitating pain and movement limitation. The aim of the study was to assess the influence of high-tone external muscle stimulation (HTEMS) therapy on clinical and electrophysiologycal parameters in hemodialysis patients with uremic peripheral neuropathy., Patients and Interventions: The study group consisted of 28 chronic hemodialysis patients (mean age 71.6 ± 8.6 y, median 74 y) on maintenance dialysis for 3 - 187 months (median 31 months). Eight persons (28.9%) were diabetics. All of them exhibited overt peripheral neuropathy and had undergone pharmacological therapy without improvement. All subjects were treated with HTEMS for 1 h during a hemodialysis session, 3 times weekly for 12 weeks. The dialysis parameters (duration of the session, blood and dialysate flow) were constant during the treatment period. Electrophysiological evaluation before and after intervention included assessment of sensory nerves (ulnar nerve, sural nerve) and motor nerves (ulnar nerve, peroneal nerve). The examined nerve conduction parameters were conduction velocity, amplitude, distal latency and F-wave latency., Results: In the questionnaire 18 persons (64%) reported improvement of general well-being after HTEMS therapy, 17 persons (61%) felt an increase of physical capacity, and 16 persons (57%) experienced a decreased feeling of cold feet. The electrophysiological findings were obtained in 19 patients who completed the examination before and after the course of HTEMS. A significant improvement was noted in the motor conduction velocity of the ulnar nerve; respective values were 48.53 ± 6.14 vs. 51.50 ± 5.51 m/s, p = 0.03., Conclusion: The study demonstrated for the first time that the subjective amelioration of uremic peripheral neuropathy by HTEMS treatment is associated with significant improvement in an objective electrophysiological parameter, motor conduction velocity of the ulnar nerve.

Background: Little is known about the influence of dynamic training on the hemodynamic and neurohormonal responses to static exercise and on inflammatory markers in optimally treated post-coronary artery bypass grafting (CABG) patients., Methods and Results: One hundred and twenty male patients, aged 55±6 years, 3 months after receiving CABG, were randomized to either 6 weeks of aerobic training on a cycloergometer, 3 times a week, at a 70-80% of the maximum tolerated heart rate (HR) (training group, n=60) or to a control group (n=60). At baseline and at the end of the study, all patients underwent: (1) a cardiopulmonary test; (2) handgrip at 30% of maximal voluntary contraction for 3min in a sitting position during in which HR, blood pressure (BP), stroke volume (SV, by impedance cardiography), cardiac output (CO) and total peripheral resistance (TPR) were monitored; and (3) plasma level assessment of catecholamines, nitric oxide and inflammatory markers. During the final tests, handgrip-induced increases in HR, BP, and TPR (14% vs 27%, P<0.01) were lower, whereas SV and CO were higher (by 13% and 15%, respectively, P<0.05) in trained patients compared with controls. Moreover, a higher increase in nitric oxide level (46% vs 14%, P<0.01) and a lower increase in noradrenaline (11% vs 20%, P<0.05) were observed in trained patients compared with controls. Accordingly, training caused significant improvement in peak oxygen uptake per kilogram body weight (peak VO(2)) and inflammatory markers., Conclusions: Short-term dynamic training caused significant improvement of hemodynamic and neurohormonal responses to handgrip, cardiovascular fitness and inflammatory state.

Aims: Despite proven benefits of cardiac rehabilitation (CR), currently proposed CR models are not acceptable for many heart failure (HF) patients. The purpose of this study was to evaluate a new model of home-based telemonitored cardiac rehabilitation (HTCR) using walking training compared with an outpatient-based standard cardiac rehabilitation (SCR) using interval training on a cycle ergometer., Methods and Results: The study included 152 HF patients (aged 58.1 + or - 10.2 years, NYHA class II and III, ejection fraction < or = 40%) who were randomized to HTCR (n = 77) or SCR (n = 75). All patients underwent 8 weeks of CR. Both groups were comparable in terms of demographic and clinical characteristics and medical therapy. The effectiveness of CR was assessed by changes in NYHA class, peak oxygen consumption, 6-min walking test distance, and SF-36 score. Cardiac rehabilitation resulted in a significant improvement of all parameters in both groups. All patients in the HTCR group completed the 8 weeks of CR, whereas 15 patients in the SCR group (20%) discontinued CR., Conclusion: In patients with HF, HTCR is equally as effective as SCR and provides a similar improvement in quality of life. Adherence to CR seems to be better for HTCR. Home-based telemonitored cardiac rehabilitation may be a useful alternative form of CR in patients with HF.

Background: Oxidative stress may promote chronic inflammation and contribute to accelerated atherogenesis in patients with coronary artery disease (CAD). Sulodexide, a glycosaminoglycan consisting primarily of heparin, has been shown to affect oxidative stress in experimental settings. The purpose of this pilot study was to determine the effect of sulodexide administration on oxidative stress, inflammation and plasma lipids in patients with proven stable CAD., Material/methods: Fifty-six optimally treated male CAD patients (pts), mean age 57+/-6 yrs, were randomized to either 8 weeks of sulodexide treatment (SUL, n=28), or to a control group (n=28). At baseline and at the end of the study, all pts underwent full clinical and standard laboratory plasma level assessment of lipids, markers of inflammation, and 8-isoprostane, as a sensitive index of oxidative stress., Results: At entry the 2 groups did not differ significantly in terms of age, coronary risk factors, clinical status and concomitant medication. SUL treatment appeared to be safe and caused a significant decrease in the level of plasma 8-isoprostane (77.4 vs 44.5 pg/ml, p<0.0001) compared with controls (75.7 vs 68.3 pg/ml, p=NS). In contrast, neither LDL cholesterol (2.71 vs 2.72 mmol/l) and triglycerides (1.38 vs 1.43 mmol/l), nor markers of inflammation - fibrinogen (3.7 vs 3.6 g/l), C-reactive protein (0.14 vs 0.13 mg/l), leukocyte count (6.33 vs 6.32x10(9)/l) - were affected by SUL treatment., Conclusions: Sulodexide administration resulted in significant reduction in oxidative stress in stable CAD patients, and neither the changes in cholesterol metabolism nor in systemic inflammation underlay this effect.

Cytotoxic T-lymphocyte antigen-4 (CTLA-4) is an important molecule in the down-regulation of T-cell activation. A study was undertaken to evaluate the association of the CTLA-4 gene polymorphisms -319C/T, +49A/G, (AT)(n), CT60A/G and Jo31G/T with the levels of membrane CTLA-4 (mCTLA-4) and cytoplasmic CTLA-4 (cCTLA-4) in CD4(+) T lymphocytes from patients with multiple sclerosis (MS) and with susceptibility to MS, and the course of the disease. It was found that the Jo31GG and CT60GG genotypes were associated with decreased mean fluorescence intensity (MFI) of total CTLA-4 (mCTLA-4 + cCTLA-4) molecules in CD4(+) T cells from both relapsing-remitting (RR) and secondary progressive (SP) MS patients compared with others. Consequently, possessing the Jo31G allele and/or the CT60G allele were associated with susceptibility to MS. The percentages of cells expressing mCTLA-4 and cCTLA-4 in RR patients were higher in carriers of the alleles non-predisposing to MS (namely CT60A and Jo31T), but the percentages of corresponding cells were unexpectedly significantly lower in SP patients than in RR patients. Increased risk of paresthesia and pyramidal signs as a first manifestation of disease, and earlier transition to the SP form in those patients, was also noted. It is hypothesized that the decreasing frequencies of cells expressing immunosuppressive mCTLA-4 and cCTLA-4 in carriers of alleles non-predisposing to MS (i.e. CT60A and Jo31T) may lead to inadequate down-regulation of ongoing T-cell responses in these patients and, as a consequence, earlier progression of disease from the RR form to the SP form.