Exercise training alone or in combination with high-protein diet in patients with late onset Pompe disease: results of a cross over study

15noBACKGROUND: Late onset Pompe disease (LOPD) is a lysosomal neuromuscular disorder which can progressively impair the patients' exercise tolerance, motor and respiratory functions, and quality of life. The available enzyme replacement therapy (ERT) does not completely counteract disease progression. We investigated the effect of exercise training alone, or associated with a high-protein diet, on the exercise tolerance, muscle and pulmonary functions, and quality of life of LOPD patients on long term ERT. METHODS: The patients were asked to participate to a crossover randomized study comprehending a control period (free diet, no exercise) followed by 2 intervention periods: exercise or exercise + diet, each lasting 26 weeks and separated by 13 weeks washout periods. Exercise training included moderate-intensity aerobic exercise on a cycle ergometer, stretching and balance exercises, strength training. The diet was composed by 25-30% protein, 30-35% carbohydrate and 35-40% fat. Before and after each period patients were assessed for: exercise tolerance test on a cycle-ergometer, serum muscle enzymes, pulmonary function tests and SF36 questionnaire for quality of life. Compliance was evaluated by training and dietary diaries. Patients were contacted weekly by researchers to optimize adherence to treatments. RESULTS: Thirteen LOPD patients, median age 49 ± 11 years, under chronic ERT (median 6.0 ± 4.0 years) were recruited. Peak aerobic power (peak pulmonary O2 uptake) decreased after control, whereas it increased after exercise, and more markedlyafter exercise + diet. Serum levels of lactate dehydrogenase (LDH) significantly decreased after exercise + diet; both creatine kinase (CK) and LDH levels were significantly reduced after exercise + diet compared to exercise. Pulmonary function showed no changes after control and exercise, whereas a significant improvement of forced expiratory volume in 1 sec (FEV1) was observed after exercise + diet. SF36 showed a slight improvement in the "mental component" scale after exercise, and a significant improvement in "general health" and "vitality" after exercise + diet. The compliance to prescriptions was higher than 70% for both diet and exercise. CONCLUSIONS: Exercise tolerance (as evaluated by peak aerobic power) showed a tendency to decrease in LOPD patients on long term ERT. Exercise training, particularly if combined with high-protein diet, could reverse this decrease and result in an improvement, which was accompanied by improved quality of life. The association of the two lifestyle interventions resulted also in a reduction of muscle enzyme levels and improved pulmonary function.openopenSechi A.; Zuccarelli L.; Grassi B.; Frangiamore R.; De Amicis R.; Marzorati M.; Porcelli S.; Tullio A.; Bacco A.; Bertoli S.; Dardis A.; Biasutti L.; Pasanisi M.B.; Devigili G.; Bembi B.Sechi, A.; Zuccarelli, L.; Grassi, B.; Frangiamore, R.; De Amicis, R.; Marzorati, M.; Porcelli, S.; Tullio, A.; Bacco, A.; Bertoli, S.; Dardis, A.; Biasutti, L.; Pasanisi, M. B.; Devigili, G.; Bembi, B

Skin Lesions on Common Bottlenose Dolphins (Tursiops truncatus) from Three Sites in the Northwest Atlantic, USA

Skin disease occurs frequently in many cetacean species across the globe; methods to categorize lesions have relied on photo-identification (photo-id), stranding, and by-catch data. The current study used photo-id data from four sampling months during 2009 to estimate skin lesion prevalence and type occurring on bottlenose dolphins (Tursiops truncatus) from three sites along the southeast United States coast [Sarasota Bay, FL (SSB); near Brunswick and Sapelo Island, GA (BSG); and near Charleston, SC (CHS)]. The prevalence of lesions was highest among BSG dolphins (P = 0.587) and lowest in SSB (P = 0.380), and the overall prevalence was significantly different among all sites (p<0.0167). Logistic regression modeling revealed a significant reduction in the odds of lesion occurrence for increasing water temperatures (OR = 0.92; 95%CI:0.906–0.938) and a significantly increased odds of lesion occurrence for BSG dolphins (OR = 1.39; 95%CI:1.203–1.614). Approximately one-third of the lesioned dolphins from each site presented with multiple types, and population differences in lesion type occurrence were observed (p<0.05). Lesions on stranded dolphins were sampled to determine the etiology of different lesion types, which included three visually distinct samples positive for herpesvirus. Although generally considered non-fatal, skin disease may be indicative of animal health or exposure to anthropogenic or environmental threats, and photo-id data provide an efficient and cost-effective approach to document the occurrence of skin lesions in free-ranging populations

Iatrogenic Kaposi’s sarcoma in myasthenia gravis: learnings from two case reports

Introduction: Myasthenia gravis (MG) is an autoimmune neuromuscular disease whose treatment encompasses acetylcholinesterase inhibitors, oral steroids, and other immunosuppressants. Kaposi’s sarcoma (KS) is a lymphangioproliferative disease associated with human herpesvirus 8 (HHV-8) infection and immunodeficiency or immunosuppression, mainly corticosteroids. Case reports: We present two cases of MG patients treated with oral steroids who developed KS. Patient 1 was diagnosed with three oral KS lesions. Prednisone was discontinued with lesion regression and stabilization, while azathioprine and pyridostigmine prompted control of MG. Patient 2 developed KS lesions on the trunk and lower limbs while taking prednisone and azathioprine. Steroid tapering was started but new oral and lymph nodal lesions appeared. Paclitaxel therapy was introduced and the patient experienced pulmonary embolism and developed sensitive neuropathy. Complete remission of KS lesions was achieved and maintained with azathioprine and pyridostigmine as MG medications. Conclusions: KS is an uncommon but clinically relevant adverse event (AE) often induced by steroid therapy. It can be controlled by steroid withdrawal but could necessitate chemotherapy, which associates with further potential AEs. Skin evaluation should be performed in all patients with chronic steroid therapy. Steroid-sparing strategies, including new drugs, could reduce KS and other steroid-related comorbidities. HHV-8 testing should be considered before starting chronic immunosuppression

Development and validation of the Myasthenia Gravis TeleScore (MGTS)

Objective: The aim of our study was to validate the Myasthenia Gravis TeleScore (MGTS), a scale for the evaluation of MG patients in telemedicine. Introduction: COVID-19 pandemic has boosted telemedicine in clinical practice. It could be crucial in the care of neurological patients with chronic disease. However, there is a lack of validated disease-specific tools to evaluate MG patients in telemedicine. Methods: The MGTS included ten items divided in four districts: ocular, generalized muscular strength, bulbar, and respiratory. Patients were assessed with two different scales: the MGTS and the INCB-MG chosen as a reference from which MGTS was partially derived. Visit in presence with INCB-MG and televisit with MGTS were performed consecutively. Televisit was conducted by another neurologist between two rooms. A blind method was adopted. The strength of correlation was determined by the correlation coefficient (r); analysis of covariance (ANOVA—Kruskal–Wallis test) was used to compare subgroups. Significance was set to p &lt; 0.05. Results: One hundred thirty-one patients were included in the study, 71 females and 60 males. The Spearman correlation coefficient between the INCB-MG scale and the MGTS was 0.825 (p &lt; 0.001), indicating a very strong correlation between them. Different items showed different correlations from low to high (0.32 to 0.80). As expected, correlation was lower between items with different evaluation modality (anamnestic vs clinical). Discussion: The MGTS demonstrated a good correlation with INCB-MG, reliability and construct validity

Evaluation of Endothelial and Vascular-Derived Progenitor Cell Populations in the Proximal and Distal UCL of the Elbow: A Comparative Study

Background: Vascular-derived progenitor and endothelial cell populations (CD31, CD34, CD146) are capable of multipotent differentiation at the site of injured ligamentous tissue to aid in the intrinsic healing response. Proximal ulnar collateral ligament (UCL) tears have been reported to have better healing capability when compared with distal UCL tears. Purpose: To compare the vascular composition of the proximal and distal insertions of the anterior bundle of the UCL of the elbow via known markers of endothelial and vascular-derived progenitor cells (CD31, CD34, CD146). Study Design: Descriptive laboratory study. Methods: UCLs were harvested from 10 nonpaired fresh-frozen human cadaveric elbows and transected into proximal and distal portions. Endothelial and vascular-derived progenitor cell densities were assessed with 4 staining groups: CD31 (immunohistochemistry) and CD31/α-smooth muscle actin (α-SMA), CD34/α-SMA, and CD146/α-SMA (immunofluorescence). CD31 immunohistochemistry identified endothelial progenitor cells in the UCL. Later staining of the same slides with α-SMA demonstrated the relationship of progenitor cells to the surrounding vasculature. Fluorescent staining was quantified by calculating the proportion of positively stained nuclei versus the total number of nuclei in the proximal and distal UCL. Results: CD31+ cells were present in the proximal and distal sections of all 10 UCLs. Fluorescent staining revealed no significant differences in the ratio of CD31 to total nuclei between the distal (median, 36% [range, 23%-53%]) and proximal UCL (39% [22%-56%]) (P = .432, Wilcoxon signed-rank test). Similarly, no differences were seen between CD34 distal (39% [24%-64%]) and proximal regions (46% [28%-63%]) (P = .846, Wilcoxon signed-rank test) or CD146 distal (40% [12%-65%]) and proximal regions (40% [22%-51%]) (P ≥ .999, Wilcoxon signed-rank test). Conclusion: Analysis of UCL tissues demonstrated equal distributions of vascular endothelial and vascular-derived progenitor cell markers throughout the proximal and distal UCL. Unlike that of the medial collateral ligament of the knee, the microvascular composition of the proximal and distal UCL insertions was not different, suggesting a well-vascularized ligament throughout its course

Early effect of dalfampridine in patients with MS: A multi-instrumental approach to better investigate responsiveness

Background: 4-aminopyridine (4-AP) is a potassium-channel blocker able to enhance walking speed in MS improving the action potentials of demyelinated axons on which internodal potassium channels are exposed.Objective: to study early 4-AP effect with clinical, subjective, neurophysiological and neuroradiological tools.Methods: Clinical (Timed 25-Foot Walk - T25FW, Timed Up-And-Go- TUG), subjective (MS Walking Scale-12 - MSWS-12), neurophysiological (Motor Evoked Potentials - MEPs) and imaging (Diffusion Tensor Imaging - DTI) evaluations were performed before (TO) and after (T1) 14 days of 4-AP treatment. MEPs were recorded from Abductor Hallucis of both legs. A Tract-Based-Spatial-Statistics (TBSS) was performed on DTI.Results: We found a significant difference between TO and T1 for T25FW, TUG, MSWS-12 (

Development and validation of the multiple sclerosis questionnaire for the evaluation of job difficulties (MSQ-Job).

Multiple sclerosis (MS) affects young adults of working age. Difficulties in work-related activities are usually ascribed to MS symptoms, while the impact of workplace features is underestimated. This article presents the Multiple Sclerosis Questionnaire for Job Difficulties (MSQ-Job), designed to assess working difficulties due to MS symptoms and workplace features.A sample of employed MS patients completed the MSQ-Job, the WHO-Disability Assessment Schedule (WHODAS 2.0) and the 54-items MS Quality of Life Questionnaires (MSQOL-54); the expanded disability status scale (EDSS) was used to define MS severity. Factor structure was evaluated using principal component extraction and Oblimin rotation; internal consistency was assessed with Cronbach's alpha; construct and discriminant validity using t-test (EDSS 0-2 vs >2; patients self-reporting need for support vs patients reporting no needs; full-time vs part-time employees); and Pearson's correlation with WHODAS 2.0 and MSQOL-54.The MSQ-Job is a 42-item questionnaire with six scales and an overall factor. Scores range on a 0-100 scale (higher scores indicate more and more severe difficulties); patients with EDSS>2 and self-reporting support needs had worse scores than those with EDSS 0-2 and without needs. Correlations with WHODAS 2.0 and MSQOL-54 were generally significant (P < 0.0007) and below 0.70.The MSQ-Job jointly measures the impact of respondents' symptoms and workplace features on work activities and enables to assess the effects of clinical and occupational interventions and better describe the impact of MS indirect costs

The Determination of Interobserver and Intraobserver Reliability of a Magnetic Resonance Imaging Based Classification System for Ulnar Collateral Ligament Injury

Background: Despite improvements in the biomechanics and surgical options for UCL tears, there remains a need for a reliable classification of UCL tears that has the potential to guide clinical decision-making. Purpose: The purpose of this cross-sectional study was to assess the intraobserver and interobserver reliability of the newly proposed MRI-based classification to UCL tears. Secondary objectives included assessing the impact of additional views, discrimination between distal and non-distal tears, and correlation of imaging reads with intraoperative findings of the UCL. Methods: Nine fellowship-trained specialists from seven institutions independently completed four series surveys consisting of 60 total elbow MRIs with UCL tears using a newly proposed six-stage classification system. The first and third surveys contained a total of 60 coronal MRI images, while the second and fourth contained the same MRI images with both coronal and axial views presented in a random order to assess intraobserver variability using the weighted kappa value and impact of additional imaging views. Weighted kappa values were also calculated for each of the four surveys to acquire interobserver reliability. Reliability analysis was repeated using a two-group classification analysis for distal and non-distal disease. Observer readings were compared to intraoperative UCL findings. Results: For the newly proposed six-stage MRI-based classification, intraobserver and interobserver reliability demonstrated near perfect and substantial agreement, respectively. These values only increased when sub-stratified into the two-group distal and non-distal disease classification (p\u3c0.05). The additional axial view did not statistically improve the agreement between and among readers. Observer readings were accurate for tear grade (partial and complete), proximal location, and distal location, but not midsubstance tears, when compared to intraoperative findings from 30 elbows. Conclusion: Our newly proposed six-stage MRI-based classification utilizing grade and location of the injury was found to have substantial to near perfect agreement between and within fellowship-trained observers. The results of this study provide a foundation for future validation studies, in which the classification system may be associated with clinical decision-making and patient outcomes. [Figure presented] Top left: 1A, proximal partial Top right: 1B, proximal complete Middle left: 2A, midsubstance partial Middle right: 2B, midsubstance complete Bottom left: 3A, distal partial Top left: 3B, distal complete [Figure presented

The Determination of Interobserver and Intraobserver Reliability of a Magnetic Resonance Imaging Based Classification System for Ulnar Collateral Ligament Injury

Background: Despite improvements in the biomechanics and surgical options for UCL tears, there remains a need for a reliable classification of UCL tears that has the potential to guide clinical decision-making. Purpose: The purpose of this cross-sectional study was to assess the intraobserver and interobserver reliability of the newly proposed MRI-based classification to UCL tears. Secondary objectives included assessing the impact of additional views, discrimination between distal and non-distal tears, and correlation of imaging reads with intraoperative findings of the UCL. Methods: Nine fellowship-trained specialists from seven institutions independently completed four series surveys consisting of 60 total elbow MRIs with UCL tears using a newly proposed six-stage classification system. The first and third surveys contained a total of 60 coronal MRI images, while the second and fourth contained the same MRI images with both coronal and axial views presented in a random order to assess intraobserver variability using the weighted kappa value and impact of additional imaging views. Weighted kappa values were also calculated for each of the four surveys to acquire interobserver reliability. Reliability analysis was repeated using a two-group classification analysis for distal and non-distal disease. Observer readings were compared to intraoperative UCL findings. Results: For the newly proposed six-stage MRI-based classification, intraobserver and interobserver reliability demonstrated near perfect and substantial agreement, respectively. These values only increased when sub-stratified into the two-group distal and non-distal disease classification (p\u3c0.05). The additional axial view did not statistically improve the agreement between and among readers. Observer readings were accurate for tear grade (partial and complete), proximal location, and distal location, but not midsubstance tears, when compared to intraoperative findings from 30 elbows. Conclusion: Our newly proposed six-stage MRI-based classification utilizing grade and location of the injury was found to have substantial to near perfect agreement between and within fellowship-trained observers. The results of this study provide a foundation for future validation studies, in which the classification system may be associated with clinical decision-making and patient outcomes