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Background: Persistent non-specific neck pain (NP) is a widespread condition described as a complex biopsychosocial disorder, characterized by physical and psychological symptoms. Virtual reality (VR) shows promise in NP treatment, potentially reducing pain, kinesiophobia, and improving range of motion (ROM) and motor control., Aim: The primary aim of the study was to assess the effectiveness of VR sensorimotor training, combined with manual therapy, in reducing the level of disability in persistent non-specific NP individuals. The secondary aim was to determine if this VR-enhanced approach also contributes to improvement in overall function, pain perception and kinesiophobia., Design: Monocentric, single-blind, randomized controlled trial., Setting: We conducted this trial at San Raffaele Scientific Institute, Department of Rehabilitation and Functional Recovery, Milan, Italy., Population: Forty NP participants were enrolled in the study and randomly allocated into two groups., Methods: The study involved a 6-week rehabilitation program, comprising 12 sessions of 45 minutes each, twice weekly. Both intervention groups underwent manual therapy as a consistent component of their treatment. The Experimental Group (VRT) was additionally engaged in sensorimotor rehabilitation exercises using Virtual Reality, whereas the Control Group (CT) performed the same exercises without VR. We assessed subjects at baseline (T0) and after six weeks of rehabilitation (T1). The primary outcome was the disability (Neck Disability Index) while the secondary outcomes were: pain perception (Numeric Rating Scale, NP and Disability Scale, Central Sensitization Inventory) function (Cervical Kinematics) and kinesiophobia (Tampa Scale of Kinesiophobia)., Results: Both groups demonstrated significant reduction in level of disability, pain perception, and kinesiophobia. Significant advancements in kinematics were observed: VRT group showed enhanced ROM during craniocervical rotation (P=0.039), lateral bending (P=0.001), flexion-extension (P=0.009), and mean velocity across movements (P<0.001), whereas CT group improved in maximal ROM during lateral bending rotation (P=0.001). Between-group analysis, after Bonferroni's correction for multiple comparisons, revealed that VRT group had significantly better outcomes in ROM during rotation (P=0.040), ratio of the primary over the secondary movement while performing rotation (P=0.021), and mean velocity during lateral bending (P=0.031)., Conclusions: Sensorimotor training, combined with manual therapy, could enhance kinematic outcomes for NP patients, supporting the potential of VR in rehabilitation., Clinical Rehabilitation Impact: This study highlighted that both groups demonstrated significant reduction in level of disability, pain perception, and kinesiophobia after sensorimotor training combined with manual therapy. It is important to underscore that in terms of reducing the level of neck disability, both interventions proved to be equally effective. This parity in efficacy is a critical finding, reaffirming the robustness of our therapeutic approaches for this specific outcome.

Background: Juvenile myasthenia gravis (JMG) is a rare autoimmune disease that causes fatigable muscle weakness in children aged <18 years. There is currently no curative treatment or internationally accepted standard of care for JMG. The objective is to investigate relationships between clinical presentation, antibody status, severity of disease onset, electrodiagnostic evaluation, and response to therapy in JMG., Methods: This study was a retrospective chart review. Congenital myasthenic syndromes were excluded. Data on demographics, treatments, and outcomes were collected. Disease severity was evaluated using Myasthenia Gravis Foundation of America (MGFA) clinical classifications., Results: We identified 84 patients with JMG at Children's Medical Center Dallas between January 2014 and February 2022. It was found that 52% of patients presented with ocular JMG (median onset age 4.5 years) and 48% with generalized JMG (median onset age 11.5 years); 81% tested positive for acetylcholine receptor antibodies. Patients were 17% non-Hispanic white, 29% Hispanic, 39% black, and 12% Asian. There was a significant difference in average MGFA scores between ethnicities (P = 0.047) and age groups (P = 0.004), with postpubertal patients having higher average MGFA scores than prepubertal patients. Seventy-one percent of patients who underwent thymectomy experienced a decrease in MGFA scores postprocedure., Conclusions: Our study showed that there were significant differences in disease severity between ethnicities and age groups and that most patients who underwent thymectomy showed clinical improvement. These outcomes highlight the need for additional therapies in the treatment of JMG and the importance of extending clinical trials to the pediatric population., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Published by Elsevier Inc.)

We report an unexpected death of a 22-year-old primigravida who was admitted to the hospital with sudden abdominal pain two days before a scheduled delivery. During an emergency caesarean section due to intrauterine asphyxia, intraabdominal bleeding was observed with no apparent source of bleeding. Newly formed blood clots in the subdiaphragmatic space and arterial bleeding near the splenic hilum required a surgery on the next day. Hemorrhagic shock led to multiple organ failure on the fourth day of admission. The autopsy revealed ruptured splenic artery at the pancreatic tail and near the splenic hilum. Microscopically, different stages of segmental arterial mediolysis were observed in partially thinned and aneurysmatic artery., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Introduction: Studies have reported health-related quality-of-life impacts of Duchenne muscular dystrophy (DMD); however, further research is needed to understand how those with DMD experience their condition and how psychosocial impacts evolve over time in response to disease progression. This qualitative study explores the social and emotional implications of key transitions, challenges and adaptations throughout the disease course from the perspective of patients and family caregivers., Methods: Semi-structured interviews were conducted with men and boys with DMD, and/or their caregivers, in the USA. Thematic analysis was used to examine patterns in data collected across the interviews., Results: Nineteen participants were included. Three major themes were identified: (1) barriers to participation are multifaceted; (2) an emotional journey shaped by 'inevitable progression;' (3) family provides critical tangible and emotional support. This study illustrates that psychosocial impacts of DMD are shaped by knowledge of the condition's natural history alongside other factors including the extent of social barriers, personal growth and adaptation, and family support., Conclusions: Findings provide insight into the strength and resilience with which individuals and their families respond to daily challenges and major clinical milestones and highlight the relative importance of loss of upper limb function as a transition in DMD affecting health-related quality-of-life., (© 2024. The Author(s).)

Background: Blunt trauma acting against the human body presents the fundamental cause of pulmonary fat embolism (PFE) and fat embolism syndrome. The aim of the present study was to investigate PFE in non-survivors after cardiopulmonary resuscitation (CPR)., Methods: This was a prospective cohort study conducted in University Hospital Ostrava, Czech Republic. Within a 4-year study period, all non-survivors after CPR because of out-of-hospital cardiac arrest were assessed for the study eligibility. The presence/seriousness of PFE was determined by microscopic examination of cryo-sections of lung tissue (staining with Oil Red O)., Results: In total, 106 persons after unsuccessful CPR were enrolled in the study. The most frequent cause of death in the study population (63.2% of cases) was cardiac disease (ischemic heart disease); PFE was not determined as the cause of death in any of our study cases. Sternal fractures were identified 66.9%, rib fractures (usually multiple) in 80.2% of study cases; the median number of rib fractures was 10.2 fractures per person. Serious intra-thoracic injuries were found in 34.9% of cases. Microscopic examination of lung cryo-sections revealed PFE in 40 (37.7%) study cases; PFE was most frequently evaluated as grade I or II. Occurrence of sternal and rib fractures was significantly higher in persons with PFE than between persons without PFE (p = 0.033 and p = <0.001). Number of rib fractures was also significantly higher in persons with PFE. The occurrence of serious intra-thoracic injuries was comparable in both our study groups (p = 0.089)., Conclusions: PFE presents a common resuscitation injury which can be found in more than 30% of persons after CPR. Persons with resuscitation skeletal chest fractures have significantly higher risk of PFE development. During autopsy of persons after unsuccessful CPR, it is necessary to distinguish CPR-associated injuries including PFE from injuries that arise from other mechanisms., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Primary progressive aphasia (PPA) diagnostic criteria underestimate the complex presentation of semantic (sv) and logopenic (lv) variants, in which symptoms partially overlap, and mixed clinical presentation (mixed-PPA) and heterogenous profile (lvPPA +) are frequent. Conceptualization of similarities and differences of these clinical conditions is still scarce., Methods: Lexical, semantic, phonological, and working memory errors from nine language tasks of sixty-seven PPA were analyzed using Profile Analysis based on Multidimensional Scaling, which allowed us to create a distributed representation of patients' linguistic performance in a shared space. Patients had been studied with [ 18 F] FDG-PET. Correlations were performed between metabolic and behavioral data., Results: Patients' profiles were distributed across a continuum. All PPA, but two, presented a lexical retrieval impairment, in terms of reduced production of verbs and nouns. svPPA patients occupied a fairly clumped space along the continuum, showing a preponderant semantic deficit, which correlated to fusiform gyrus hypometabolism, while only few presented working memory deficits. Adjacently, lvPPA + presented a semantic impairment combined with phonological deficits, which correlated with metabolism in the anterior fusiform gyrus and posterior middle temporal gyrus. Starting from the shared phonological deficit side, a large portion of the space was occupied by all lvPPA, showing a combination of phonological, lexical, and working memory deficits, with the latter correlating with posterior temporo-parietal hypometabolism. Mixed PPA did not show unique profile, distributing across the space., Discussion: Different clinical PPA entities exist but overlaps are frequent. Identifying shared and unique clinical markers is critical for research and clinical practice. Further research is needed to identify the role of genetic and pathological factors in such distribution, including also higher sample size of less represented groups., (© 2024. The Author(s).)

Introduction: Evaluating the neural correlates of sensorimotor control deficits in cervical dystonia (CD) is fundamental to plan the best treatment. This study aims to assess kinematic and resting-state functional connectivity (RS-FC) characteristics in CD patients relative to healthy controls., Methods: Seventeen CD patients and 14 age-/sex-matched healthy controls were recruited. Electromagnetic sensors were used to evaluate dystonic pattern, mean/maximal cervical movement amplitude and joint position error with eyes open and closed, and movement quality during target reaching with the head. RS-fMRI was acquired to compare the FC of brain sensorimotor regions between patients and controls. In patients, correlations between motion analysis and FC data were assessed., Results: CD patients relative to controls showed reduced mean and maximal cervical range of motion (RoM) in rotation both towards and against dystonia pattern and reduced total RoM in rotation both with eyes open and closed. They had less severe dystonia pattern with eyes open vs eyes closed. CD patients showed an altered movement quality and sensorimotor control during target reaching and a higher joint position error. Compared to controls, CD patients showed reduced FC between supplementary motor area (SMA), occipital and cerebellar areas, which correlated with lower cervical RoM in rotation both with eyes open and closed and with worse movement quality during target reaching., Conclusions: FC alterations between SMA and occipital and cerebellar areas may represent the neural basis of cervical sensorimotor control deficits in CD patients. Electromagnetic sensors and RS-fMRI might be promising tools to monitor CD and assess the efficacy of rehabilitative interventions., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Elisabetta Sarasso reports a relationship with Italian Ministry of Health that includes: funding grants. Daniele Emedoli reports a relationship with Khymeia Group S.R.L that includes: consulting or advisory and speaking and lecture fees. Andrea Gardoni reports a relationship with none that includes:. Lucia Zenere reports a relationship with None that includes:. Elisa Canu reports a relationship with Italian Ministry of Health that includes: funding grants. Silvia Basaia reports a relationship with Italian Ministry of Health that includes: funding grants. Alberto Doretti reports a relationship with AbbVie Inc, Eli Lilly, TEVA, Lundbeck that includes: consulting or advisory. Nicola Ticozzi reports a relationship with None that includes:. Sandro Iannaccone reports a relationship with None that includes:. Stefano Amadio reports a relationship with None that includes:. Ubaldo Del Carro reports a relationship with None that includes:. Massimo Filippi reports a relationship with Alexion, Almirall, Bayer, Biogen, BMS, Celgene, Chiesi Italia SpA, Eli Lilly, Genzyme, Janssen, Merck, Neopharmed Gentili, Novartis, Novo Nordisk, Roche, Sanofi, Takeda, TEVA, Italian Ministry of Health, Italian Ministry of University and Research, FISM that includes: consulting or advisory, funding grants, and speaking and lecture fees. Federica Agosta reports a relationship with Biogen Idec, Italfarmaco, Roche, Zambon, Ely Lilli, Italian Ministry of Health, Italian Ministry of University and Research, AriSLA, the European Research Council, the EU JPND, and Foundation Research on Alzheimer Disease (France) that includes: funding grants and speaking and lecture fees. M. Filippi is Editor-in-Chief of the Journal of Neurology, Associate Editor of Human Brain Mapping, Neurological Sciences, and Radiology; F. Agosta is Associate Editor of NeuroImage: Clinical If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Introduction: Anodal transcranial Direct Current Stimulation (tDCS) is a non-invasive, low-cost and environment-friendly brain neuromodulation technique that increases cortical excitability. In post-stroke aphasia, the role of the right hemisphere in language recovery remains debated. In this preliminary study, we aimed to investigate the efficacy of excitatory tDCS on the right hemisphere in chronic aphasic patients., Methods: We applied anodal tDCS to the right homologous region of Broca's area in four chronic aphasic patients while performing a one-month naming rehabilitation treatment. Longitudinal data on language assessment and naming performance were collected. Resting-state fMRI images were acquired before and after treatment to measure changes in functional connectivity., Results: Results showed enhanced positive functional connectivity of the right Broca homologous with the left middle frontal and middle temporal gyri. Every patient showed improvements in language functions, but no major changes in naming performance., Conclusion: These preliminary findings suggest that tDCS applied over the unaffected hemisphere may result in longitudinal inter-hemispheric functional neuroplastic changes that could specifically improve language recovery and could potentially be included in therapeutic neurorehabilitative plans., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Alemanno, Fedeli, Monti, Houdayer, Della Rosa, Zangrillo, Emedoli, Pelagallo, Corbo, Iannaccone and Abutalebi.)

Introduction: The COVID-19 pandemic impacted public health and our lifestyles, leading to new social adaptations such as quarantine, social distancing, and facial masks. Face masks, covering extended facial zones, hamper our ability to extract relevant socio-emotional information from others' faces. In this fMRI study, we investigated how face masks interfere with facial emotion recognition, focusing on brain responses and connectivity patterns as a function of the presence of a face mask., Methods: A total of 25 healthy participants (13F; mean age: 32.64 ± 7.24y; mean education: 18.28 ± 1.31y) were included. Participants underwent task-related fMRI during the presentation of images of faces expressing basic emotions (joy or fear versus neutral expression). Half of the faces were covered by a face mask. Subjects had to recognize the facial emotion (masked or unmasked). FMRI whole-brain and regions-of-interest analyses were performed, as well as psychophysiological interaction analysis (PPI)., Results: Subjects recognized better and faster emotions on unmasked faces. FMRI analyses showed that masked faces induced a stronger activation of a right occipito-temporal cluster, including the fusiform gyrus and the occipital face area bilaterally. The same activation pattern was found for the neutral masked > neutral unmasked contrast. PPI analyses of the masked > unmasked contrast showed, in the right occipital face area, a stronger correlation with the left superior frontal gyrus, left precentral gyrus, left superior parietal lobe, and the right supramarginal gyrus., Discussion: Our study showed how our brain differentially struggles to recognize face-masked basic emotions, implementing more neural resources to correctly categorize those incomplete facial expressions., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Abutalebi, Gallo, Fedeli, Houdayer, Zangrillo, Emedoli, Spina, Bellini, Del Maschio, Iannaccone and Alemanno.)

Introduction: During the pandemic, the Cognitive Disorders Unit of San Raffaele Hospital (Milan, Italy) offered patients the opportunity to undergo neuropsychological evaluations and cognitive training through telemedicine., Method: We conducted an investigation to assess how patients responded to this option and to determine if telemedicine could ensure continuity of care., Results: Between October 2019 and May 2022, a total of 5,768 telemedicine appointments and 8,190 in-person outpatient appointments were conducted, resulting in an increase in the rate of telemedicine activity from 16.81% in January 2020 to 23.21% in May 2022. Peaks in telemedicine activity reached 85.64% in May 2020 and 83.65% in February 2021, both representing a significant portion of the total activity. Interestingly, there was a notable positive correlation between telemedicine activity and the worsening of the Italian pandemic ( r  = 0.433, p  = 0.027)., Discussion: During the peaks of contagion, the total number of visits remained stable, highlighting that telemedicine effectively served as a valuable and efficient tool to ensure continuity of care for vulnerable patients. This was evident from the integration of remote visits with in-person appointments., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Emedoli, Houdayer, Della Rosa, Zito, Brugliera, Cimino, Padul, Tettamanti, Iannaccone and Alemanno.)

Background: Becker muscular dystrophy is an X-linked, genetic disorder causing progressive degeneration of skeletal and cardiac muscle, with a widely variable phenotype., Objective: A 3-year, longitudinal, prospective dataset contributed by patients with confirmed Becker muscular dystrophy was analyzed to characterize the natural history of this disorder. A better understanding of the natural history is crucial to rigorous therapeutic trials., Methods: A cohort of 83 patients with Becker muscular dystrophy (5-75 years at baseline) were followed for up to 3 years with annual assessments. Muscle and pulmonary function outcomes were analyzed herein. Age-stratified statistical analysis and modeling were conducted to analyze cross-sectional data, time-to-event data, and longitudinal data to characterize these clinical outcomes., Results: Deletion mutations of dystrophin exons 45-47 or 45-48 were most common. Subgroup analysis showed greater pairwise association between motor outcomes at baseline than association between these outcomes and age. Stronger correlations between outcomes for adults than for those under 18 years were also observed. Using cross-sectional binning analysis, a ceiling effect was seen for North Star Ambulatory Assessment but not for other functional outcomes. Longitudinal analysis showed a decline in percentage predicted forced vital capacity over the life span. There was relative stability or improved median function for motor functional outcomes through childhood and adolescence and decreasing function with age thereafter., Conclusions: There is variable progression of outcomes resulting in significant heterogeneity of the clinical phenotype of Becker muscular dystrophy. Disease progression is largely manifest in adulthood. There are implications for clinical trial design revealed by this longitudinal analysis of a Becker natural history dataset.

he aim of our research is to prove, that the transplanted hepatocytes can survive and compensate for inadequate liver function in experimental animals. Thesis discusses the basic principles of hepatocyte transplantations, the process of their adaptation and effect on the organism as well as possibilities of their further use as a promising treatment method.In the experiment we used hepatocytes isolated and produced from explanted livers of laboratory rats. Hepatocytes form the basis of liver tissue and are responsible for a number of metabolic processes ocurring in the liver, therefore is the possibility of their use as a cell therapy one of the alternative treatment methods for liver failure.Into the laboratory experiment, rats of the Sprague Dawleyspecies were placed, which we divided into five groups of equal numbers. Groups consisted of healthy rats, rats after 2/3 liver resection and rats with liver damage induced by intraperitoneal administration of thioacetamide.Two groups with impaired liver had hepatocytes prepared in advance transplanted into their portal vein.Hepatocyte function was assessed in the blood serum and compared with a control group of healthy animals and groups with liver damage without the application of hepatocytes at the same time intervals.Whole experiment lasted 21 days. On the last day of the experiment all the animals were killed by decapitation.Livers of all animals were explanted and sent for histopathological analysis which used classical histological methods. After evaluating the results we observed significant changes of evaluated laboratory levels in blood serum and weight in experimental animals after the transplantation of hepatocytes in comparison with the laboratory results of the control group of healthy animals and groups with liver damage without transplanted hepatocytes. The results of our experiment show that by biochemical and histological analysis we managed to clearly prove the function of transplanted hepatocytes in the model of laboratory rat with impaired liver function (Tab. 5, Fig. 17 , Ref. 17) Keywords: liver, transplantation, hepatocytes, liver tumors, resection of liver, liver failure, experiment.

Background: Although social cognitive dysfunction is a major feature of the behavioral variant of frontotemporal dementia (bvFTD), quantitative measurement of social behavior changes is poorly available in clinical settings., Objective: The aim of the study is to evaluate diagnostic accuracy of social-emotional questionnaires in distinguishing bvFTD from healthy control (HC) subjects and Alzheimer's disease (AD) patients., Methods: We enrolled 29 bvFTD, 24 AD, and 18 HC subjects matched for age, sex, and education. Two informant-based measures of socio-emotional sensitivity and empathy (i.e., revised Self-Monitoring Scale (rSMS) and Interpersonal Reactivity Index (IRI)) were administered. One-way ANOVA was performed to compare groups, whereas Receiver Operating Characteristics (ROC) curve analysis tested questionnaire ability in distinguishing groups. A short version of IRI (sIRI) was obtained by excluding the non-contributing subscale (i.e., personal distress)., Results: Compared to HC and AD, bvFTD showed significantly lower scores in rSMS and IRI scores, except for IRI personal distress subscale. The sIRI showed an excellent performance in early diagnosis (bvFTD versus HC = AUC 0.95). Both sIRI and rSMS showed good performance in distinguishing bvFTD from AD (AUC 0.83)., Conclusions: ROC analyses support the usefulness of informant social questionnaires in memory clinics and their potential value in screening procedures for research eligibility in forthcoming trials. In the timely diagnosis of bvFTD patients, IRI and rSMS may supply crucial information for the early detection of signs and symptoms affecting social-emotional skills, which might otherwise be underrecognized.

Self-stabbing and self-cutting represents an uncommon method of suicide. We present a case of a 30-year-old man who was found dead in the forest. The body was naked and showed multiple cut and stab wounds on different parts of the body (face, neck, chest, abdomen, and extremities). A single-edged kitchen knife was found approximately 20 m from the body. Parts of both ears, the fifth toe of the right foot, and the scrotum were cut off. At the autopsy, two of the severed body parts-the toe and the part of the left ear-were found in the stomach. The cause of death was asphyxiation due to blood aspiration resulting from a cut throat injury. A police investigation uncovered a history of substance abuse and two previous suicidal attempts using a knife. Upon complex analysis of all the evidence, the manner of death was ruled a suicide, which was preceded by actions of major self-mutilation and self-cannibalism, both considered rare behavioral patterns., (© 2023. The Author(s).)

The hypothesis that the effectiveness of neurosurgical procedures in Parkinson's disease (PD) would be related to connectivity dysfunctions between the site of the stimulation and other brain regions is growing. This study aimed to assess resting-state functional connectivity between thalamic ventral intermediate nucleus (Vim) and the rest of the brain before and after thalamotomy in PD. A 76-year-old right-handed woman with refractory tremor-dominant PD was selected as a candidate for left Vim radiosurgery thalamotomy. Clinical and motion sensor evaluation and brain resting-state functional MRI (rs-fMRI) were carried out before treatment and 3, 6, and 12 months later. Targeted Vim was selected as region of interest and a seed-based rs-fMRI analysis was performed in the patient and ten age- and sex-matched controls at baseline and over time. Furthermore, a correlation analysis between functional connectivity and tremor data was carried out. Both clinical and motion sensor measurements showed a progressive tremor improvement over time on right side after radiosurgery. In the patient, seed-based analysis showed a significantly increased functional connectivity between targeted Vim and ipsilateral visual areas relative to controls before treatment. Over 1 year, a normalization of aberrant pre-therapeutic functional connectivity between Vim and visual areas was obtained. At correlation analysis, the reduction of tremor metrics over time, assessed by clinical evaluation and wearable motion sensors, was related to the reduction of the left Vim-left visual cortex functional connectivity. Our findings support the evidence that fMRI was able to detect targeted Vim connectivity and its changes over time after thalamotomy., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

The multidisciplinary assessment of hospitalized patients via validated scales and tools has become crucial in the early identification of sarcopenia. The objective of this study was to determine the prevalence of sarcopenia and its related factors in patients aged ≥65 years admitted to the neurological rehabilitation departments of cognitive motor disorders and functional motor rehabilitation at the IRCCS Hospital San Raffaele in Milan. Using the algorithm reported by the European Working Group on Sarcopenia in Older People (EWGSOP2), the prevalence of sarcopenia in patients was investigated from 2019-2020. Definite sarcopenia was detected in 161 of 336 recruited patients (47.9%). Age was significantly higher in sarcopenic patients than in those without sarcopenia (median 81 vs. 79 years, p < 0.001) and height, weight, and body mass index were lower ( p < 0.001 for all). The malnutrition screening test (MUST) was higher but still negative in most sarcopenic patients (47.8% vs. 20.6%, p < 0.001). Patients with sarcopenia had significantly reduced life autonomy (by Barthel index, median 55 vs. 60 points, p < 0.001) and increased mental impairment (tested by MMSE and MOCA, p < 0.005 for both). In conclusion, sarcopenic patients were more cognitively impaired and less autonomous in their daily life, but the majority presented with a negative malnutrition screening test.

Competing Interests: The authors report no conflict of interest.

Introduction: Differentiating between the two most common forms of dementia, Alzheimer's dementia and dementia with Lewy bodies (DLB) remains difficult and requires the use of invasive, expensive, and resource-intensive techniques. We aimed to investigate the sensitivity and specificity of electroencephalography quantified using the statistical pattern recognition method (qEEG-SPR) for identifying dementia and DLB., Methods: Thirty-two outpatients and 16 controls underwent clinical assessment (by two blinded neurologists), EEG recording, and a 6-month follow-up clinical assessment. EEG data were processed using a qEEG-SPR protocol to derive a Dementia Index (positive or negative) and DLB index (positive or negative) for each participant which was compared against the diagnosis given at clinical assessment. Confusion matrices were used to calculate sensitivity, specificity, and predictive values for identifying dementia and DLB specifically., Results: Clinical assessment identified 30 cases of dementia, 2 of which were diagnosed clinically with possible DLB, 14 with probable DLB and DLB was excluded in 14 patients. qEEG-SPR confirmed the dementia diagnosis in 26 out of the 32 patients and led to 6.3% of false positives (FP) and 9.4% of false negatives (FN). qEEG-SPR was used to provide a DLB diagnosis among patients who received a positive or inconclusive result of Dementia index and led to 13.6% of FP and 13.6% of FN. Confusion matrices indicated a sensitivity of 80%, a specificity of 89%, a positive predictive value of 92%, a negative predictive value of 72%, and an accuracy of 83% to diagnose dementia. The DLB index showed a sensitivity of 60%, a specificity of 90%, a positive predictive value of 75%, a negative predictive value of 81%, and an accuracy of 75%. Neuropsychological scores did not differ significantly between DLB and non- DLB patients. Head trauma or story of stroke were identified as possible causes of FP results for DLB diagnosis., Conclusion: qEEG-SPR is a sensitive and specific tool for diagnosing dementia and differentiating DLB from other forms of dementia in the initial state. This non-invasive, low-cost, and environmentally friendly method is a promising diagnostic tool for dementia diagnosis which could be implemented in local care settings., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Iannaccone, Houdayer, Spina, Nocera and Alemanno.)

Rationale: World healthcare frequently faced severe viral pneumonia cases in the last decades, due to pandemic situations such as H1N1, MERS-CoV, and SARS-COVID-19., Patient Concerns: The impact of viral infection on lung structure, lung function, and overall mortality was significant. The quality of life and assumed life expectancy was decreased with the supposed development of lung fibrosis in involved survived patients., Diagnoses: We described the course and treatment of severe pneumonia H1N1 in a 30-year-old patient., Interventions: Patient was included in a study regarding the therapeutic efficacy of selenium ClinicalTrials.gov ID: NCT02026856 with 10 years follow-up with concurrently documented X-ray lung examinations and final histology of lung tissue after sudden death., Outcomes: All sequential examinations and histological findings show a healing trend with the final full recovery of lung tissue., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Objective: We aimed to investigate the clinical symptoms and specific care requirements of SARS-CoV-2 patients who were admitted to a COVID-19 Rehabilitation Unit while still infectious for SARS-CoV-2 and in the subacute phase of the disease., Methods: Patients admitted to our COVID-19 Rehabilitation Unit from March 2020 to December 2020 were evaluated for sarcopenia, and they also completed the following assessments: functional independence measure, short physical performance battery and Hamilton Rating Scale for Depression. Age and body mass index and symptoms of dysosmia or dysgeusia were also recorded., Results: A total of 126 patients were enrolled (50 women, median age 72 years, 18.7 years), of whom 82% of patients presented with low grip strength. Sarcopenia was diagnosed in 52 patients. Sarcopenic patients were older than non-sarcopenic ones (median age 73.4 years, IQR 13.2 vs 63.9 years, IQR 14.5, respectively, p = 0.014). Sarcopenia was associated with the presence of depression ( p = 0.008), was more common in women ( p = 0.023) and was associated with greater functional deficits (functional independence measure and short physical performance battery analyses, p < 0.05). Sarcopenic patients also had a lower body mass index than other patients ( p < 0.01)., Conclusion: More than 40% of our patients suffered from sarcopenia, which was associated with ageing, depression, low body mass index, reduction in functional autonomy and being a woman. Such data provide evidence for the need to assist hospitalized COVID-19 patients by means of a multidisciplinary specialist team., Competing Interests: The authors have no conflicts of interest to declare., (© Published by Medical Journals Sweden, on behalf of the Foundation for Rehabilitation Information.)

This article reports the autopsy findings of a 1.5-year-old girl with no history of previous hospital admission who suddenly collapsed at home. After 45 minutes of resuscitation efforts, the cardiac activity was restored. During hospitalization, she had ventricular arrhythmia and extremely elevated cardiac troponin levels. Internal examination and immunohistochemistry revealed cardiac fibromas of the right and left ventricles and extensive hypoxic myocardial damage. The right ventricular fibroma demonstrated interdigitating and entrapped myocardium visible at the edges and within the central portion of the tumor. The left ventricular fibroma originated in the subepicardial region and propagated towards the endocardium., Competing Interests: Conflict of interestD. Farkaš, M. Pisarčíková, P. Vasovčák, A. Crhová, A. Ginelliová, L. Mistríková, L. Fröhlichová and S. Farkašová Iannaccone declare that they have no competing interests., (© The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature 2023.)

Primary progressive aphasia (PPA) classification relies on profile characterization of quantitatively impaired/spared performance in language tasks. In this study, we coextracted 8 qualitative types of errors in 67 PPA patients submitted to a comprehensive language assessment. Canonical correlation analysis was applied to simultaneously correlate qualitative errors and brain metabolism, collected with FDG-PET. Results showed the contribution of semantic, syntactic and working memory errors associated with specific correlates of regional metabolic changes. Reduced metabolism in the left fusiform gyrus, anterior-middle and inferior-temporal gyri and middle-temporal pole correlated with an increase of semantic errors. Hypometabolism in the left inferior, middle, and superior frontal gyri, insula and right middle-occipital gyrus was related to syntactic errors. Higher metabolism in the bilateral pallidum, putamen, and left thalamus, as well as hypometabolism in the left angular and supramarginal gyri, inferior-parietal lobule, posterior-middle and inferior-temporal gyri and posterior cingulum predicted the increase of working memory errors. A relevant role of working memory subcomponents was associated with distinct neural systems. Patients' profiles are easily represented in a qualitative multidimensional space, in which mixed PPA overlapped with different phenotypes., (Copyright © 2022. Published by Elsevier Inc.)

Background: This study's primary aim was to evaluate the impact of thrombotic complications on the development of secondary infections. The secondary aim was to compare the etiology of secondary infections in patients with and without thrombotic complications., Methods: This was a cohort study (NCT04318366) of coronavirus disease 2019 (COVID-19) patients hospitalized at IRCCS San Raffaele Hospital between February 25 and June 30, 2020. Incidence rates (IRs) were calculated by univariable Poisson regression as the number of cases per 1000 person-days of follow-up (PDFU) with 95% confidence intervals. The cumulative incidence functions of secondary infections according to thrombotic complications were compared with Gray's method accounting for competing risk of death. A multivariable Fine-Gray model was applied to assess factors associated with risk of secondary infections., Results: Overall, 109/904 patients had 176 secondary infections (IR, 10.0; 95% CI, 8.8-11.5; per 1000-PDFU). The IRs of secondary infections among patients with or without thrombotic complications were 15.0 (95% CI, 10.7-21.0) and 9.3 (95% CI, 7.9-11.0) per 1000-PDFU, respectively ( P  = .017). At multivariable analysis, thrombotic complications were associated with the development of secondary infections (subdistribution hazard ratio, 1.788; 95% CI, 1.018-3.140; P  = .043). The etiology of secondary infections was similar in patients with and without thrombotic complications., Conclusions: In patients with COVID-19, thrombotic complications were associated with a high risk of secondary infections., Competing Interests: Potential conflicts of interest. A.C. has received consultancy payments and speaking fees from Bristol-Myers Squibb, Gilead, ViiV Healthcare, Merck Sharp & Dohme, and Janssen-Cilag. All other authors declare that they have no conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Functional network-level alterations in the semantic variant of Primary Progressive Aphasia (sv-PPA) are relevant to understanding the clinical features and the neural spreading of the pathology. We assessed the effect of neurodegeneration on brain systems reorganization in early sv-PPA, using advanced brain metabolic connectivity approaches. Forty-four subjects with sv-PPA and forty-four age-matched healthy controls (HC) were included. We applied two multivariate approaches to [18F]FDG-PET data - i.e., sparse inverse covariance estimation and seed-based interregional correlation analysis - to assess the integrity of (i) the whole-brain metabolic connectivity and (ii) the connectivity of brain regions relevant for cognitive and behavioral functions. Whole-brain analysis revealed a global-scale connectivity reconfiguration in sv-PPA, with widespread changes in metabolic connections of frontal, temporal, and parietal regions. In comparison to HC, the seed-based analysis revealed a) functional isolation of the left anterior temporal lobe (ATL), b) decreases in temporo-occipital connections and contralateral homologous regions, c) connectivity increases to the dorsal parietal cortex from the spared posterior temporal cortex, d) a disruption of the large-scale limbic brain networks. In sv-PPA, the severe functional derangement of the left ATL may lead to an extensive connectivity reconfiguration, encompassing several brain regions, including those not yet affected by neurodegeneration. These findings support the hypothesis that in sv-PPA the focal vulnerability of the core region (i.e., ATL) can potentially drive the widespread cerebral connectivity changes, already present in the early phase., Competing Interests: Declaration of competing interest No competing financial interests exist., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

A smartphone application (Medico-Amico) has been developed by the collaboration of San Raffaele Scientific Institute and Khymeia Group S.R.L. with the aim of providing physical exercises and communicating with patients after their hospitalization in a coronavirus disease (COVID)-rehabilitation unit. Thirty patients used the application for remote rehabilitation for 4 weeks. They were prescribed personalized motor exercises to perform three times a week. Clinicians could interact with each patient by an encrypted video call in order to give encouragement, mental support, modify intensity during training sessions, or to prescribe new exercises. Patients were asked to perform motor exercises and also to monitor their vital signs, such as temperature, blood pressure, and oxygen saturation, inserting scores in a specific section of the application. After 4 weeks of remote rehabilitation patients showed improvements in independence during activity of daily living and strength. Also, satisfaction and mobile application usability scores reached patients' appreciation and enjoyment., Competing Interests: D. Emedoli received compensation for consulting services, speaking activities and clinical development from Khymeia Group S.R.L. The other authors declared no potential conflicts of interest with respect to the research, authorship and/or publication of this article., (© 2022 The Authors. Healthcare Technology Letters published by John Wiley & Sons Ltd on behalf of The Institution of Engineering and Technology.)

Inflammatory bowel disease (IBD) is a group of disorders causing inflammation in the digestive tract. Recent data suggest that dysbiosis may play a pivotal role in the IBD pathogenesis. As microbiome-based therapeutics that modulate the gut ecology have been proposed as a novel strategy for preventing IBD, the aim of presenting study was to evaluate the dextran sulphate sodium (DSS) rat model mainly in terms of microbial shifts to confirm its suitability for dysbiosis study in IBD. Acute colitis was induced using 5% DSS solution for seven days and rats were euthanized five days after DSS removal. The faecal/caecal microbiota was analyzed by next generation sequencing. Disease activity index (DAI) score was evaluated daily. Blood and colon tissue immunophenotyping was assessed by flow cytometry and histological, haematological, and biochemical parameters were also evaluated. The colitis induction was reflected in a significantly higher DAI score and changes in all parameters measured. This study demonstrated significant shifts in the colitis-related microbial species after colitis induction. The characteristic inflammation-associated microbiota could be detected even after a five day-recovery period. Moreover, the DSS-model might contribute to an understanding of the effect of different treatments on extraintestinal organ impairments. The observation that certain bacterial species in the gut microbiota are associated with colitis raises the question of whether these organisms are contributors to, or a consequence of the disease. Despite some limitations, we confirmed the suitability of DSS-induced colitis model to monitor microbial changes during acute colitis, in order to test attractive new microbiome-based therapies.

Phosphorylated TDP-43 (pTDP-43) aggregates in the cytoplasm of motor neurons and neuroglia in the brain are one of the pathological hallmarks of amyotrophic lateral sclerosis. Although the axons exceed the total volume of motor neuron soma by several orders of magnitude, systematic studies investigating the presence and distribution of pTDP-43 aggregates within motor nerves are still lacking. The aim of this study is to define the TDP-43/pTDP-43 pathology in diagnostic motor nerve biopsies performed on a large cohort of patients presenting with a lower motor neuron syndrome and to assess whether this might be a discriminating tissue biomarker for amyotrophic lateral sclerosis and non-amyotrophic lateral sclerosis cases. We retrospectively evaluated 102 lower motor neuron syndrome patients referred to our centre for a diagnostic motor nerve biopsy. Histopathological criteria of motor neuron disease and motor neuropathy were applied by two independent evaluators, who were blind to clinical data. TDP-43 and pTDP-43 were evaluated by immunohistochemistry, and results compared to final clinical diagnosis. We detected significant differences between amyotrophic lateral sclerosis and non-amyotrophic lateral sclerosis cases in pTDP-43 expression in myelinated fibres: axonal accumulation was detected in 98.2% of patients with amyotrophic lateral sclerosis versus 30.4% of non-amyotrophic lateral sclerosis samples (P < 0.0001), while concomitant positive staining in Schwan cell cytoplasm was found in 70.2% of patients with amyotrophic lateral sclerosis versus 17.4% of patients who did not have amyotrophic lateral sclerosis (P < 0.001). Importantly, we were also able to detect pTDP-43 aggregates in amyotrophic lateral sclerosis cases displaying normal features at standard histopathological analysis. Our findings demonstrated that a specific pTDP-43 signature is present in the peripheral nervous system of patients with amyotrophic lateral sclerosis, and could be exploited as a specific, accessible tissue biomarker. The detection of pTDP-43 aggregates within motor nerves of living patients with amyotrophic lateral sclerosis, occurring before axonal degeneration, suggests that this is an early event that may contribute to amyotrophic lateral sclerosis pathogenesis., (© The Author(s) (2021). Published by Oxford University Press on behalf of the Guarantors of Brain.)

Mental alterations were described during the COVID-19 pandemic and sleep deprivation has been reported as a consequence of social isolation. In Italy, the COVID-19 pandemic spread out at the beginning of 2020 determining severe lockdown periods. The aim of our study was to observe the effects of lockdown on sleep and anxiety in trained non-professional subjects and professional athletes who continued to train during the lockdown period. Forty-six subjects (21 trained non-professional subjects and 25 professional athletes) were recruited from a variety of team and individual sports to complete a battery of previously validated and widely used questionnaires assessing psychometric and anthropometric parameters, physical activity levels, lifestyle habits, and sleep quality. Subjects were aged 27.0 ± 5.14. All items were evaluated as percentages and chi-square and Fisher’s exact tests were performed, as appropriate. Our data showed that the prevalence of the difficulty of falling asleep (over 30%), the tendency of nocturnal awakenings (over 30%), and moderate anxiety (over 38%) were at the same extent in the two groups. Of the professional athletes, 72.73% declared snoring during sleep vs 42.86% of non-professional subjects. No other significant differences were found between the two groups except for the perception of being constant in daily activity, significantly more reported by trained subjects (p < 0.005). Our data show a similar scenario of anxiety and sleep disturbances for the two groups, suggesting that lockdown by the COVID-19 pandemic has partially mitigated the known beneficial effects due to physical activity on mental health and sleep quality. Further analyses are necessary to define the associated risk factors.

Objective: Late-onset amnestic mild cognitive impairment (aMCI) with long disease course and slow progression has been recently recognized as a possible phenotypical expression of a limbic-predominant neurodegenerative disorder. Basic emotion recognition ability crucially depending on temporo-limbic integrity is supposed to be impaired in this group of MCI subjects presenting a selective vulnerability of medio-temporal and limbic regions. However, no study specifically investigated this issue., Methods: Hereby, we enrolled 30 aMCI with a biomarker-based diagnosis of Alzheimer's disease (i.e., aMCI-AD, n = 16) or a biomarker evidence of selective medio-temporal and limbic degeneration (aMCI-mTLD, n = 14). Ekman-60 Faces Test (Ek-60F) was administered to each subject, comparing the performance with that of 20 healthy controls (HCs)., Results: aMCI-mTLD subjects showed significantly lower Ek-60F global scores compared to HC (p = 0.001), whose performance was comparable to aMCI-AD. Fear (p = 0.02), surprise (p = 0.005), and anger (p = 0.01) recognition deficits characterized the aMCI-mTLD performance. Fear recognition scores were significantly lower in aMCI-mTLD compared to aMCI-AD (p = 0.04), while no differences were found in other emotions., Conclusions: Impaired social cognition, suggested by defective performance in emotion recognition tasks, may be a useful cognitive marker to detect limbic-predominant aMCI subjects among the heterogeneous aMCI population.

Background: Data on the clinical course of Duchenne muscular dystrophy (DMD) exist from well-characterized clinical cohorts but estimates from real-world populations are fewer., Objective: The objective was to estimate the prevalence of key clinical milestones by age, among real-world commercially-insured DMD patients in the United States., Methods: MarketScan claims (2013-2018) were used to identify males with DMD. The percentages with wheelchair use or experiencing scoliosis, neurologic/neuropsychiatric involvement, cardiomyopathy, and respiratory involvement were tabulated; as were the median (interquartile range [IQR]) ages at first observed occurrence within the claims data., Results: Among DMD patients (n = 1,964), the median (IQR) baseline age was 15 (9-21) years, and median follow-up was 1.7 years. Wheelchair use was observed in 55% of those aged 8 to 13 years at cohort entry; scoliosis, among 38% of those 8 to 10 and 52% of those 11 to 13 years; neurologic/neuropsychiatric involvement, among 41-43% of those 8 to 13 years; respiratory involvement, among 45% of those 14 to 19 years; and cardiomyopathy, among 68% of those 14 to 16 and 58% of those 17 to 19 years., Conclusions: The prevalence of key clinical milestones across ages was broadly consistent with published findings. Variability in estimates reflect clinical heterogeneity; these contemporary estimates from real-world data help characterize clinical outcomes in DMD.

Background: The Frontal Behavioral Inventory (FBI) is a questionnaire designed to quantify behavioral changes in frontotemporal dementia (FTD). Literature showed heterogeneous FBI profiles in FTD versus Alzheimer's disease (AD) with variable occurrence of positive and negative symptoms., Objective: In this study, we constructed a short FBI version (i.e., mini-FBI) with the aim to provide clinicians with a brief tool for the identification of early behavioral changes in behavioral variant of FTD (bvFTD), also facilitating the differential diagnosis with AD., Methods: 40 bvFTD and 33 AD patients were enrolled. FBI items were selected based on internal consistency and exploratory factor analysis. Convergent validity of mini-FBI was also assessed. A behavioral index (i.e., B-index) representing the balance between positive and negative mini-FBI symptoms was computed in order to analyze its distribution in bvFTD through a cluster analysis and to compare performance among patient groups., Results: The final version of the mini-FBI included 12 items, showing a significant convergent validity with the Neuropsychiatric Inventory scores (rp = 0.61, p &lt; 0.001). Cluster analysis split patients in four clusters. bvFTD were included in three different clusters characterized by prevalent positive symptoms, both positive and negative symptoms, or prevalent negative behavioral alterations, similar to a subset of AD patients. A fourth cluster included only AD patients showing no positive symptoms., Conclusion: The mini-FBI is a valuable easily administrable questionnaire able to early identify symptoms effectively contributing to the bvFTD behavioral syndrome, aiding clinician in diagnosis and management.

Trigeminal neuralgia (TN) is the most frequent craniofacial pain condition, which commonly affects patients suffering from multiple sclerosis (MS). Stereotactic radiosurgery, especially Gamma Knife radiosurgery (GKRS), represents a safe and effective treatment for TN, and it has been adopted also for MS-TN, with a lower success rate. Therefore, we aimed to analyze the outcome of GKRS for MS-TN. PubMed, Web of Science, and Google Scholar and the reference list of relevant articles were searched for GKRS in MS-TN. Two investigators independently identified the articles, assessed the study quality, and extracted the data. Endpoints of interest were initial pain responders, successful treatments at the end of follow-up, and factors influencing the outcome. Data analyses were performed using R software. Twelve articles involving 646 patients met our inclusion criteria. Pooled proportion of patients who experienced an initial response to GKRS treatment was 83% (CI 74-90%). The cumulative proportion of successful treatments at the end of follow-up was 47% (CI 33-60%). No variables were found to have a significant contribution to heterogeneity regarding the initial response outcome. The only variable significantly explaining the heterogeneity found in the proportion of successful treatments was the length of the follow-up, with a negative b coefficient (- 0.0051, p value = 0.0047). Regarding the efficacy of GKRS in MS-TN, the initial pain response rate was 83%, which dramatically decreases to 47% during follow-up. GKRS still represents a valuable option for MS-TN; however, its long-term efficacy should be always considered., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH, DE part of Springer Nature.)

BACKGROUND: Duchenne muscular dystrophy (DMD) is a severe X-linked progressive neurodegenerative disease characterized by loss of ambulation, cardiomyopathy, respiratory insufficiency, and early mortality. Few data are available that describe the direct medical costs among patients with DMD in the United States. OBJECTIVE: To characterize the demographics, comorbidity burden, and direct monthly costs of care among patients with DMD with Medicaid and with commercial insurance coverage. METHODS: IBM MarketScan Commercial and Multi-State Medicaid claims (2013-2018) were used to identify males aged 30 years or under with diagnostic codes for muscular dystrophy or DMD; additional exclusion criteria were applied to identify those with probable DMD. Baseline characteristics and comorbidities were tabulated. The frequency of health care resource use and median (interquartile range [IQR]) monthly costs (in 2018 USD) were estimated from those with at least 12 months of continuous follow-up. RESULTS: Median (IQR) baseline ages were similar between the Medicaid (14 [9-20] years; n = 2,007) and commercial (15 [9-21] years; n = 1,964) DMD cohorts. The frequency of comorbidities over the period was slightly higher with those on Medicaid. The median duration of follow-up was 3.1 years among members of the Medicaid DMD cohort and 1.7 years among the commercial DMD cohort. Median monthly resource use was generally higher among the Medicaid DMD cohort; nonetheless, median (IQR) monthly costs were similar at $1,735 ($367-$5,281) for the Medicaid DMD cohort vs $1,883 ($657-$6,796) for the commercial DMD cohort. CONCLUSIONS: The demographic characteristics and median direct medical costs were similar between patients with commercial vs Medicaid coverage, even though patients with Medicaid coverage had higher resource use. Despite challenges in definitively identifying DMD patients using claims data, these findings help characterize contemporary DMD populations in the United States and the related direct economic burden to the payer. DISCLOSURES: This study was funded by Sarepta Therapeutics, Inc. Klimchak and Gooch are employees of Sarepta Therapeutics Inc. Szabo, Qian, and Popoff are employees of Broadstreet HEOR, which received funds from Sarepta Therapeutics, Inc., for work on this study. Iannaccone has received research funding or consulting fees from Avexis, Biogen, Fibrogen, Mallinkrodt, Regeneron, Sarepta Therapeutics, Inc., Scholar Rock, PTC Therapeutics, Pfizer, MDA, CureSMA, NIH, Genentech-Roche, and BCBS. Publication of the study results was not contingent on the sponsor's approval or censorship of the manuscript. Information from this study was presented, in part, at the AMCP Virtual Annual Meeting, April 21-24, 2020.