Nonambulatory Patients Research Articles

Hip reduction surgery versus scoliosis correction in non-ambulant neuromuscular patients: which surgery is the first step?

Children and young adults with neuromuscular disorders have a high incidence of both spine and hip deformities. The aim of this study was to evaluate the outcome of either primary scoliosis or hip surgery in children and young adults with neuromuscular disorders. A retrospective study was conducted on all children and young adults with neuromuscular-related synchronous hip subluxation/dislocation and scoliosis undergoing hip or scoliosis surgery in our institution between 2012 and 2021 with a minimum follow-up of 24months. Demographic and operative data were collected; radiological parameters were measured preoperatively and postoperatively at final follow-up. Forty neuromuscular patients with synchronous hip displacement and scoliosis were included. Twenty patients with an average age of10.2years had hip correction surgery performed primarily, with a mean follow-up of 54.9 (24-96)months. The other 20 patients with an average age of 12.4years had scoliosis correction first, with a mean follow-up of 40 (24-60)months. In the "Hip first" group, pelvic obliquity, hip MP and Cobb angle were 16.8°, 71%, and 49°, respectively. At final follow-up, the mean pelvic obliquity and Cobb angles significantly progressed to 27.2° (p = 0.003) and 82.2° (p = 0.001), respectively. Eighteen patients (90%) required scoliosis correction after the hip surgery. In the "Scoliosis first" group, the mean pelvic obliquity, hip MP and Cobb angle were 21.2°, 49% and 65.5°, respectively. At final follow-up, both pelvic obliquity and Cobb angle significantly improved to 8.44° (p = 0.002) and 23.4° (p = 0.001), respectively. In 11/20 (55%) patients, the hip MP had significantly increased following the spinal surgery to 62% (p = 0.001), but only 5/20 (25%) patients underwent hip surgery after scoliosis correction. In neuromuscular patients presenting with synchronous hip displacement and scoliosis deformity, corrective scoliosis surgery is associated with a significant correction of pelvic obliquity and lower rates of secondary hip surgery. On the other hand, primary hip surgery does not reduce the risk of pelvic obliquity and scoliosis deformity progression.

Characteristics of femoral neck fractures in osteogenesis imperfecta: Series of four-teen consecutive hips in twelve patients

IntroductionWhile long bone fractures are commonly seen in individuals with Osteogenesis Imperfecta (OI), femoral neck fractures (FNF) are exceedingly rare. There is a lack of comprehensive data regarding the etiology of FNFs, their characteristics, and the treatment protocols. Our aim was to determine the characteristics of femoral neck fractures in children with OI. Materials and methodsThis study was conducted as retrospective series covering period of January 2011-December 2022. Total of 14 femoral neck fractures in 12 patients were included into final analysis. Age, gender, fracture location, ambulation level, injury mechanism, Sillence type, pre-fracture collo-diaphyseal angle, presence of previous implants and applied treatments were noted. ResultsThe mean age was 9.3 (range: 3–16), 8 out of 12 patients were males. Sillence type 3 OI was most common (50 %) type. Among 12 patients, 2 (16.6 %) were restricted ambulatory while 5 (41.6 %) were non-ambulatory. Seven patients had prior femoral implants. Six fractures were managed non-operatively, while others underwent surgery, with cannulated screws (42.8 %) or plate osteosynthesis (7.1 %). All eight cases (100 %) with minor trauma or unknown origin were Sillence type 3–4, displaying varus deformity. FNFs that occured in mobile patients required higher-energy traumas. ConclusionFemoral neck fractures in OI showed differing trauma mechanisms in ambulatory vs. non-ambulatory patients. Non-surgical treatment may be considered with in patients with high-risk anesthesia concerns, requiring higher level clinical studies.

Severe rigid hip flexion-abduction contracture in cerebral palsy: a case report and review of the literature.

severe, rigid hip abduction deformity in individuals with cerebral palsy (CP) is an exceptionally uncommon condition. This posture hinders the positioning in the wheelchair and the completion of basic activities of daily living (ADL). Addressing such severe deformities can be quite challenging. a 14-year-old male, with spastic-dystonic quadriplegic CP, developed rigid and severe flexion-abduction contractures in both hips, characterized by 90 degrees of flexion and 100 degrees of abduction. These contractures severely impeded his ability to comfortably use a wheelchair and even pass through doorways. Performing basic ADLs became a significant challenge for both the patient and his caregivers. the treatment approach involved a two-stage surgical procedure, one for each hip, with a two-month interval between them. An extensive release of the fascia latae, gluteus maximus, external rotators, and hip flexors; in combination with a proximal femur osteotomy were performed. To maintain the corrections achieved, long-leg casts connected with two bars were employed, followed by orthotic support and physiotherapy. Following the procedure, lower limb adduction was achieved, and the patient and caregivers were highly satisfied, as ADLs and basic caregiving had been greatly facilitated. while the available literature on the management of severe rigid abduction hip contractures in non-ambulatory CP patients is limited, and treatment options are often complex, the present case underscores the effectiveness of a comprehensive approach involving soft tissue release and bone surgery. Achieving a more favorable wheelchair positioning and facilitating basic ADLs and care represents a significant success for patients and families.

Quantitative muscle ultrasound in adult spinal muscular atrophy. A pilot study.

Muscle ultrasound has been investigated in children with spinal muscular atrophy (SMA) and proposed as a potential biomarker of disease severity. We studied the ultrasound properties in adults with SMA to see whether they also have potential as markers of disease severity in older patients. Thickness and quantitative echogenicity of muscle and subcutaneous tissue were compared between eight prospectively recruited adult patients with SMA and eight age, sex and body mass index-matched controls. Measurements were made in the dominant deltoid, biceps, triceps, forearm extensors, first dorsal interosseous, quadriceps, tibialis anterior, and gastrocnemius muscles. The muscle-to-subcutaneous (M:S) thickness and echogenicity ratios were also calculated. A mean value across all muscles as well as the individual values for each muscle were then calculated for each parameter in each subject and compared between the two groups. Significance was set at 0.05 after Bonferroni correction. In the SMA patients, mean muscle thickness was significantly smaller (1.3 vs. 1.9 cm), muscle echogenicity higher (106 vs. 67 on the grayscale level), and subcutaneous thickness larger (0.9 vs. 0.3 cm) than in controls; M:S echogenicity ratio was significantly increased and M:S thickness ratio reduced in the patients. The most abnormal scores were found in the nonambulatory patients and the least abnormal in the ambulatory patients. Ultrasound can detect and quantify the severity of muscle atrophy and structure in adult SMA, suggesting a potential role as a marker of disease severity, which will require validation by larger studies.

Impact of metastatic epidural spinal cord compression (MESCC) and pathological vertebral compression fracture (pVCF) in neurological and survival prognosis

BackgroundMetastatic epidural spinal cord compression (MESCC) and pathological vertebral compression fractures (pVCF) are the most serious debilitating morbidities of spine metastases (SpMs) causing devastating neurological damages. The respective impact of these two metastasis-spreading entities on survival and on neurological damage is debated. MethodsA French prospective cohort study collected 279 consecutive patients presenting with SpMs between January 2017 and 2021. We compared 174 patients with MESCC and 105 patients with pVCF. ResultsThe median Overall Survival (OS) for the MESCC group was 13.4 months (SD 1.5) vs 19.2 months (SD 2.3) for pVCF patients (p = 0.085). Sixty-five patients (23.3 %) were operated on: 49/65 (75.4 %) in the MESCC group and 16/65 (15.2 %) in the pVCF group, p < 0.0001. At 6 months FU, in the MESCC group, 21/44 (45.4 %) of non-ambulatory patients at onset improved to ambulatory status (Frankel D-E) vs 10/13 (76.9 %) in the pVCF group (p = 0.007). In multivariable analysis with the Cox proportional hazard model, good ECOG-PS and SINS Score 7–12 [HR: 6.755, 95 % CI 2.40–19.00; p = 0.001] were good prognostic factors for preserved ambulatory neurological status. However, SpMs diagnosed synchronously with the primary tumor [HR: 0.397, 95 % CI 0.185–0.853; p = 0.018] and MESCC [HR: 0.058, 95 % CI 0.107–0.456; p = 0.007] were independent risk factors for impaired neurological function. ConclusionContrary to pVCF, MESCC causes neurological damage. Nevertheless, neurological recovery remains possible. MESCC and pVCF have no impact on survival. The management of MESCC remains to be clarified and optimized to reduce neurological damage.

Estimating health state utilities in Duchenne muscular dystrophy using the health utilities index and EQ-5D-5L

BackgroundThe progression of Duchenne muscular dystrophy (DMD) is characterized by loss of ambulation, respiratory insufficiency, cardiomyopathy, and early mortality. DMD profoundly impacts health-related quality-of-life (HRQoL). However, few health state utility data exist; published utilities tend to be derived from small samples for a limited number of health states and are often based on caregiver-reported patient health status. This study estimated utility values for varied clinical and functional health states in DMD, based on patient-reported health status.MethodsIndividuals with DMD in the US aged 12–40 years completed the EQ-5D (5-level) and Health Utilities Index (HUI) preference-based instruments. Based on responses to a clinical questionnaire, participants self-classified into functional health states according to level of lower and upper limb function, use of respiratory support, and presence of cardiomyopathy. Mean [standard deviation (SD)] utility and EQ-5D visual analogue scale (VAS) scores were estimated according to health state; and median (interquartile range) attribute levels calculated to understand which domains of health are most severely affected in DMD.ResultsOf 63 males with DMD, mean (SD) age was 19.8 (6.1) years and 11 (17.5%) were ambulatory. Mean (SD) utility values were 0.92 (0.08; HUI2), 0.84 (0.20; HUI3), and 0.84 (0.13; EQ-5D) for ambulatory patients without cardiomyopathy (n = 10). For non-ambulatory patients with moderately impaired upper limb function, night and daytime ventilation without cardiomyopathy, mean (SD) utilities were 0.49 (0.07) for the HUI2, 0.16 (0.15) for the HUI3 and 025 (0.14) for the EQ-5D. Mean (SD) VAS scores for the same health states were 91 (9) and 83 (21), respectively. In addition to impairments in mobility/ambulation, and self-care, attributes like usual activities and pain also showed notable effects of DMD.ConclusionsIn DMD, although a relationship between disease progression and HRQoL is observed, there is large variability in utility within functional health states, and across instruments. Utility values for less severe non-ambulatory health states described by level of upper limb function are novel. These utility values, derived based on direct patient feedback rather than from caregiver report, are relevant to individuals of varying functional statuses and augment scarce DMD-specific utility data.

A qualitative study to understand the Duchenne muscular dystrophy experience from the parent/patient perspective

BackgroundDuchenne muscular dystrophy (DMD) is a rare, severe, fatal neuromuscular disease characterized by progressive atrophy and muscle weakness, resulting in loss of ambulation, decreased upper body function, and impaired cardiorespiratory function. This study aimed to generate qualitative evidence to describe the primary symptoms and impacts of DMD in ambulatory and non-ambulatory patients as reported by patient/caregiver dyads. Information was also gathered on expectations for future DMD treatments.MethodsForty-six dyads (caregiver and patients with DMD aged 4 to 22 years) participated in 60-min semi-structured video interviews. Interview transcripts were analyzed using thematic analysis. Differences in experiences with DMD by ambulation status were examined.ResultsMean ages of ambulatory (n = 28) and non-ambulatory participants (n = 18) were 8.7 and 11.3 years, respectively, with an average age of diagnosis of 3.7 years (SD = 2.3). The primary symptoms reported by both groups were lack of strength (ambulatory: n = 28, 100.0%; non-ambulatory: n = 17, 94.4%) and fatigue (ambulatory: n = 24, 85.7%; non-ambulatory: n = 14, 77.8%). Physical function was the domain that was most impacted by DMD, with participants describing progressive decline of physical function due to loss of physical strength as the primary defining feature of the disease across all stages of ambulatory ability. For those who maintained ambulatory ability at the time of the interview, physical function impacts described impaired mobility (e.g., climbing stairs: n = 16, 57.1%; running: n = 13, 46.4%), impaired upper body function, in particular fine motor skills like holding a pen/pencil or buttoning clothes (n = 17, 60.7%), problem with transfers (e.g., getting off the floor: n = 10, 35.7%), and activities of daily living (ADLs; n = 15, 53.6%). For non-ambulatory participants, the functional impacts most frequently described were problems with transfers (e.g., getting in/out of bed: n = 13, 72.2%; getting in/out of chair or position in bed: both n = 10, 55.6%), impaired upper body function (reaching: n = 14, 77.8%), and ADLs (n = 15, 83.3%). Meaningful treatment goals differed by ambulatory status; for ambulatory participants, goals included maintaining current functioning (n = 20, 71.4%), improving muscle strength (n = 7, 25.9%), and reducing fatigue (n = 6, 22.2%). For non-ambulatory participants, these included increased upper body strength (n = 8, 42.1%) and greater independence in ADLs (n = 6, 31.6%). A preliminary conceptual model was developed to illustrate the primary symptoms and physical function impacts of DMD and capture their relationship to disease progression.ConclusionThis study contributes to the limited qualitative literature by characterizing impacts of physical limitations and symptoms of DMD on disease progression and thus providing insights into the lived experience with DMD. Differences in treatment goals were also identified based on ambulatory status. Taken together, these findings can help inform patient-centered measurement strategies for evaluating outcomes in DMD clinical research.

Assessing the Assisted Six-Minute Cycling Test as a Measure of Endurance in Non-Ambulatory Patients with Spinal Muscular Atrophy (SMA).

Assessing endurance in non-ambulatory individuals with Spinal Muscular Atrophy (SMA) has been challenging due to limited evaluation tools. The Assisted 6-Minute Cycling Test (A6MCT) is an upper limb ergometer assessment used in other neurologic disorders to measure endurance. To study the performance of the A6MCT in the non-ambulatory SMA population, prospective data was collected on 38 individuals with SMA (13 sitters; 25 non-sitters), aged 5 to 74 years (mean = 30.3; SD = 14.1). The clinical measures used were A6MCT, Revised Upper Limb Module (RULM), Adapted Test of Neuromuscular Disorders (ATEND), and Egen Klassifikation Scale 2 (EK2). Perceived fatigue was assessed using the Fatigue Severity Scale (FSS), and effort was assessed using the Rate of Perceived Exertion (RPE). Data were analyzed for: (1) Feasibility, (2) Clinical discrimination, and (3) Associations between A6MCT with clinical characteristics and outcomes. Results showed the A6MCT was feasible for 95% of the tested subjects, discriminated between functional groups (p = 0.0086), and was significantly associated with results obtained from RULM, ATEND, EK2, and Brooke (p < 0.0001; p = 0.029; p < 0.001; p = 0.005). These findings indicate the A6MCT's potential to evaluate muscular endurance in non-ambulatory SMA individuals, complementing clinician-rated assessments. Nevertheless, further validation with a larger dataset is needed for broader application.

Total Knee Replacement in Nonambulant Patients: Osteoporosis, Severe Fixed Flexion Deformity, and Weak Extensor Mechanism “the Terrible Triad”

Abstract Background: Knee osteoarthritis is among the most disabling disorders in elderly. With delay in proper management, muscular weakness, progressive flexion deformity (FD), and disuse osteoporosis “the terrible triad” are serious consequences, which could be major obstacles for the planned total knee replacements (TKRs). High risk for iatrogenic fractures, difficult gap balancing and failure to promote the patient activity are common expectations. Materials and Methods: A retrospective analysis of all TKRs that were done in a university specialized unit between January 2015 and January 2021 searching for nonambulant-patients was done. Twenty-two replacements for 15 patients who were unable to walk at least 3 months before surgery were found. The median fixed FD (FFD) before anesthesia was 45°. Osteopenia was evident on X-rays and bone thickness intraoperatively. Quadriceps muscle strength was not more than grade four. The median preoperative functional KSS was 0°. The median preoperative WOMAC score was 90.63. Results: Twelve knees had remaining FFD 1 year after surgery with a median of 5°. Ten had iatrogenic fractures mostly affected the medial femoral condyle. One patient could not regain walking capability and 11 patients could not walk without assistance. The median postoperative functional KSS and WOMAC scores were 61 and 21.36, respectively. Conclusion: TKRs in nonambulant patients with evident terrible triad (muscle weakness, osteoporosis, and FFD) is a risky procedure. Common complications include iatrogenic fractures and inability to regain normal physical capabilities. Despite the magnificent improvement in function, we do not recommend performing TKRs in such patients without strict patient counseling with possible drawbacks.

Gain and loss of upper limb abilities in Duchenne muscular dystrophy patients: A 24-month study

Duchenne muscular dystrophy (DMD) is a neuromuscular condition characterized by muscle weakness. The Performance of upper limb (PUL) test is designed to evaluate upper limb function in DMD patients across three domains. The aim of this study is to identify frequently lost or gained PUL 2.0 abilities at distinct functional stages in DMD patients. This retrospective study analyzed prospectively collected data on 24-month PUL 2.0 changes related to ambulatory function. Ambulant patients were categorized based on initial 6MWT distance, non-ambulant patients by time since ambulation loss. Each PUL 2.0 item was classified as shift up, no change, or shift down. The study's cohort incuded 274 patients, with 626 paired evaluations at the 24-month mark. Among these, 55.1 % had activity loss, while 29.1 % had gains. Ambulant patients showed the lowest loss rates, mainly in the shoulder domain. The highest loss rate was in the shoulder domain in the transitioning subgroup and in elbow and distal domains in the non-ambulant patients. Younger ambulant patients demonstrated multiple gains, whereas in the other functional subgroups there were fewer gains, mostly tied to singular activities. Our findings highlight divergent upper limb domain progression, partly linked to functional status and baseline function.

Self-reported functioning among patients with ultra-rare nemaline myopathy or a related disorder in Finland: a pilot study

BackgroundNemaline myopathy (NM) and related disorders (NMr) form a heterogenous group of ultra-rare (1:50,000 live births or less) congenital muscle disorders. To elucidate the self-reported physical, psychological, and social functioning in the daily lives of adult persons with congenital muscle disorders, we designed a survey using items primarily from the Patient Reported Outcomes Measurement Information System, PROMIS®, and conducted a pilot study in patients with NM and NMr in Finland. The items were linked to International Classification of Functioning, Disability and Health (ICF) categories.ResultsIn total, 20 (62.5%) out of 32 invited persons resident in Finland participated in the study; 12 had NM and 8 NMr, 15 were women and 5 men aged 19–75 years. Sixteen (80%) were ambulatory and 4 (20%) NM patients used wheelchairs. The results from the PROMIS measuring system and ICF categories both indicated that non-ambulatory patients of this study faced more challenges in all areas of functioning than ambulatory ones, but the differences were smaller in the domains measuring psychological and social functioning than in physical functioning. In addition, the COVID-19 pandemic adversely affected the functioning of non-ambulatory patients more than that of ambulatory patients. The interindividual differences were, however, noticeable.ConclusionsTo our knowledge, this pilot study is the first comprehensive survey-based study of the physical, psychological, and social functioning of adult persons with nemaline myopathy or related disorders. The results indicate vulnerability of non-ambulatory patients being at higher risk to a decrease in general functioning during global or national exceptional periods. The responses also gave directions for modifying and improving the survey for future studies.

Validating Recorded EHR and Actual Weight: Single Institution Study

Abstract Introduction/Objective Our hemapheresis clinic performs outpatient and inpatient therapeutic apheresis procedures including red blood cell exchange and therapeutic plasma exchange. Accurate height, weight, and hematocrit are required for calculating replacement fluid volumes for both procedures. Our practice has been using the patient’s most recent weight recorded in the EHR. The purpose of this quality improvement project is to validate concordance between patients’ actual body weight and documented body weight. Methods/Case Report STUDY DESIGN AND DATA COLLECTION We performed this quality improvement project in our hemapheresis clinic. The study focused on weight variations impacting calculations for apheresis volume requirements. Data were collected from March 20th, 2023 – April 20th, 2023. Patients receiving red blood cell exchange or therapeutic plasma exchange were randomly selected and weighed prior to the procedure on a calibrated scale. The most recently recorded weight in the EHR was also collected. Non-ambulatory patients or patients receiving phlebotomy or stem cell collection were excluded from the study. Statistical Analysis: Statistical analyses were performed using R Statistical Software (Foundation for Statistical Computing, Vienna, Austria). We compared means of two observations using a paired t-test. P values less than 0.05 were considered to be statistically significant to test null hypothesis. Results (if a Case Study enter NA) A total of 40 patient data were collected. Seventeen male and 23 female patients were weighed and recorded. The mean value of EHR weight is 70.56kg and that of clinic weight is 71.41kg (P=0.08701). The weight discrepancy was calculated in comparison with EHR recorded weight and it was transformed to weight discrepancy by percentage using d(clinic weight -EHR weight)/clinic weight*100. Out of 40 patients, 33 patients had weight discrepancy by percentage between 0 to 4%. Conclusion Patient body weight is an important factor in calculating the replacement volume requirements in therapeutic apheresis. It is often prescribed based on the recorded EHR weight. In our data, we have shown that the weight discrepancy is not significant and therefore EHR recorded weight is reliable in replacement volume calculation. Our study is subject to several limitations that it was conducted for one month in a single institution and the sample size is not large. However, our study is novel in describing the relationship between recorded patient data and the actual patient data.

Assessment of Motor Unit Potentials Duration as the Biomarker of DT-DEC01 Cell Therapy Efficacy in Duchenne Muscular Dystrophy Patients up to 12 Months After Systemic–Intraosseous Administration

Duchenne muscular dystrophy (DMD) is a lethal X-linked disease caused by mutations in the dystrophin gene, leading to muscle degeneration and wasting. Electromyography (EMG) is an objective electrophysiological biomarker of muscle fiber function in muscular dystrophies. A novel, DT-DEC01 therapy, consisting of Dystrophin Expressing Chimeric (DEC) cells created by fusing allogeneic myoblasts from normal donors with autologous myoblasts from DMD-affected patients, was assessed for safety and preliminary efficacy in boys of age 6–15 years old (n = 3). Assessments included EMG testing of selected muscles of upper (deltoideus, biceps brachii) and lower (rectus femoris and gastrocnemius) extremities at the screening visit and at 3, 6, and 12 months following systemic–intraosseous administration of a single low dose of DT-DEC01 therapy (Bioethics Committee approval no. 46/2019). No immunosuppression was administered. Safety of DT-DEC01 was confirmed by the lack of therapy-related Adverse Events or Serious Adverse Events up to 22 months following DT-DEC01 administration. EMG of selected muscles of both, ambulatory and non-ambulatory patients confirmed preliminary efficacy of DT-DEC01 therapy by an increase in motor unit potentials (MUP) duration, amplitudes, and polyphasic MUPs at 12 months. This study confirmed EMG as a reliable and objective biomarker of functional assessment in DMD patients after intraosseous administration of the novel DT-DEC01 therapy.

P237 Prevalence and progression of scoliosis in non-ambulant paediatric patients with Duchenne muscular dystrophy on various glucocorticoid treatments

P237 Prevalence and progression of scoliosis in non-ambulant paediatric patients with Duchenne muscular dystrophy on various glucocorticoid treatments

P148 Analysis of upper limb functional outcomes in a single centre paediatric cohort of non-ambulatory patients with Duchenne muscular dystrophy

P148 Analysis of upper limb functional outcomes in a single centre paediatric cohort of non-ambulatory patients with Duchenne muscular dystrophy

Movement Disorders in Patients With Genetic Developmental and Epileptic Encephalopathies.

Movement disorders (MDs) are underrecognized in the developmental and epileptic encephalopathies (DEEs). There are now more than 800 genes implicated in causing the DEEs; relatively few of these rare genetic diseases are known to be associated with MDs. We identified patients with genetic DEEs who had MDs, classified the nature of their MDs, and asked whether specific patterns correlated with the underlying mechanism. We classified the type of MDs associated with specific genetic DEEs in a large international cohort of patients and analyzed whether specific patterns of MDs reflected the underlying biological dysfunction. Our cohort comprised 77 patients with a genetic DEE with a median age of 9 (range 1-38) years. Stereotypies (37/77, 48%) and dystonia (34/77, 44%) were the most frequent MDs, followed by chorea (18/77, 23%), myoclonus (14/77, 18%), ataxia (9/77, 12%), tremor (7/77, 9%), and hypokinesia (6/77, 8%). In 47% of patients, a combination of MDs was seen. The MDs were first observed at a median age of 18 months (range day 2-35 years). Dystonia was more likely to be observed in nonambulatory patients, while ataxia was less likely. In 46% of patients, therapy was initiated with medication (34/77, 44%), deep brain stimulation (1/77, 1%), or intrathecal baclofen (1/77, 1%). We found that patients with channelopathies or synaptic vesicle trafficking defects were more likely to experience dystonia; whereas, stereotypies were most frequent in individuals with transcriptional defects. MDs are often underrecognized in patients with genetic DEEs, but recognition is critical for the management of these complex neurologic diseases. Distinguishing MDs from epileptic seizures is important in tailoring patient treatment. Understanding which MDs occur with different biological mechanisms will inform early diagnosis and management.

Safety and Efficacy of DT-DEC01 Therapy in Duchenne Muscular Dystrophy Patients: A 12 - Month Follow-Up Study After Systemic Intraosseous Administration

Duchenne Muscular Dystrophy (DMD) is a progressive and fatal muscle-wasting disease with no known cure. We previously reported the preliminary safety and efficacy up to six months after the administration of DT-DEC01, a novel Dystrophin Expressing Chimeric (DEC) cell therapy created by fusion of myoblasts of DMD patient and the normal donor. In this 12-month follow-up study, we report on the safety and functional outcomes of three DMD patients after the systemic intraosseous administration of DT-DEC01. The safety of DT-DEC01 was confirmed by the absence of Adverse Events (AE) and Severe Adverse Events (SAE) up to 21 months after intraosseous DT-DEC01 administration. The lack of presence of anti-HLA antibodies and Donors Specific Antibodies (DSA) further confirmed DT-DEC01 therapy safety. Functional assessments in ambulatory patients revealed improvements in 6-Minute Walk Test (6MWT) and timed functions of North Star Ambulatory Assessment (NSAA). Additionally, improvements in PUL2.0 test and grip strength correlated with increased Motor Unit Potentials (MUP) duration recorded by Electromyography (EMG) in both ambulatory and non-ambulatory patients. DT-DEC01 systemic effect was confirmed by improved cardiac and pulmonary parameters and daily activity recordings. This follow-up study confirmed the safety and preliminary efficacy of DT-DEC01 therapy in DMD-affected patients up to 12 months after intraosseous administration. DT-DEC01 introduces a novel concept of personalized myoblast-based cellular therapy that is irrespective of the mutation type, does not require immunosuppression or the use of viral vectors, and carries no risk of off target mutations. This establishes DT-DEC01 as a promising and universally effective treatment option for all DMD patients.Graphical

DESIGN AND ORGANIZATION OF AN INTERPROFESSIONAL NETWORK FOR HOME MANAGEMENT OF PATIENTS IMPLEMENTED DURING COVID-19 PANDEMIC AT ASL NAPOLI 2 NORD, SUITABLE ALSO IN THE DAILY MANAGEMENT OF CHRONIC PATIENTS LIVING IN THE SAME AREA

Introduction: The Coronavirus SARS-CoV-2 pandemic has altered the perception of the current National Health Service (SSN). On one hand, the importance of a free and always accessible SSN for everyone has been strengthened. On the other hand, the fragility of a system with a too specialized and hospital-centered approach has become evident. In the pandemic context, the need to reverse the model by focusing on the needs of the community has become clear, with the main aim of promoting home-based management as much as possible for both chronic and acute conditions. This can be achieved through the creation of an integrated network involving all stakeholders in the care and assistance process, utilizing new technologies and telemedicine systems.Materials and Methods: The aim of this activity was to delve into an integrated network model for home care of Covid patients, within ASL Napoli 2 Nord. This model utilizes interconnected and functionally integrated structures and nodes, with defined pathways and operational procedures based on dedicated telemedicine platforms. These platforms facilitate the comprehensive management and care of Covid-19 patients by all network stakeholders. Results were monitored using specific and dedicated indicators, collecting and analysing data from the period when the care of positive Covid patients began (November 2020), whose management did not require hospitalization.Results: From November 2020 to December 2021, the number of patients living in the ASL Napoli 2 Nord territory under home management included Home Health Care Units (USCA), non-ambulatory residential facilities undergoing non-pharmacological therapy (TNF), non-ambulatory vaccinated individuals receiving home vaccination, and vaccinated individuals in residential facilities, amounted to 38,223. Among these, 37.8% (14,476) tested positive for Covid.The total number of accesses during this period was approximately 94,000, encompassing various types of care provided (TNF at home, TNF in facilities, home management of Covid+ patients, vaccinations in facilities, vaccinations at home for non-ambulatory patients). The shift has been significant, transitioning from managing the entirety of patients in hospitals to slightly over 4.5% of the total managed from December 2020 to December 2021. Conclusions: The sensitivity of healthcare managers during the pandemic period translated into the realization that the focus of the National Health System (SSN) and the Regional Health System (SSR) needed to shift, directing efforts increasingly towards the implementation of local healthcare policies.The high number of hospitalizations recorded was not solely due to the increased number of infections, but also to the challenges faced in providing home care. Creating, developing, and continually implementing an interdisciplinary and interprofessional network, coupled with the development of technological infrastructures and more, ensured the ability to address the emergency. This guaranteed that all citizens received the necessary care and assistance to navigate this historically critical and unexpected moment.The reproducibility of this system assures the possibility of further network implementation, not only in emergencies but also for the daily management of chronic patients. Moreover, in a time when, among other things, Mission 6 of the National Recovery and Resilience Plan (PNRR) has allocated resources amounting to 15.63 billion euros to be invested in the healthcare sector, most of which are dedicated to revolutionizing our SSN and ensuring its greater efficiency and effectiveness in the territor.

A leaky gut contributes to postural dysfunction in patients with Alzheimer's disease

BackgroundPostural dysfunction is a common problem in patients with Alzheimer's disease (AD) and may lead to functional dependency and increasing morbidity and mortality. However, the pathophysiology of postural dysfunction in AD patients remains poorly understood. ObjectivesElevated intestinal permeability is an underlying contributor to multiple diseases, including AD. We aimed to investigate the association of elevated intestinal permeability with postural dysfunction in AD patients. Design Setting, Participants, MeasurementsWe conducted a cross-sectional, observational study on older adults, including controls and AD patients. We investigated the associations of postural balance with plasma zonulin, a marker of elevated intestinal permeability in geriatric controls (n = 74) and patients with mild (n = 71) and moderate (n = 66) AD. We used a standardized physical performance battery to measure balance in supine, tandem, and semi-tandem positions. We also measured handgrip strength (HGS), and gait speed as markers of physical capacity. ResultsAD patients exhibited lower balance scores, HGS, and gait speed and higher plasma zonulin than in controls (all p < 0.05). Plasma zonulin levels demonstrated significant areas under the curves in diagnosing poor balance in AD patients (all p < 0.05). Moderate AD was associated with lower balance and physical capacity, and higher zonulin than mild AD (ALL P < 0.05). Poor scores on balance scale were associated with higher expressions of markers of inflammation, oxidative stress, and muscle damage providing a mechanistic link between increased intestinal permeability and postural dysfunction in AD patients. ConclusionThe results of our study show that plasma zonulin measurement may be used to diagnose postural dysfunction in AD patients. The study is relevant to non-ambulant and/or comatose AD patients with postural dysfunction. Our findings also highlight the therapeutic potential of repairing the intestinal leak to improve postural control and reduce the risk of falls in AD patients.

Management and Outcomes of Femur Fractures in Patients with Duchenne Muscular Dystrophy

Background: Duchenne muscular dystrophy (DMD) is a severe, progressive X-linked recessive neuromuscular disorder characterized by muscle weakness and atrophy. Additionally, patients with DMD have significant reductions in bone mineral density compared to age-matched controls, which is exacerbated by concomitant steroid use. These findings dramatically increase fracture risk, which may irreparably decrease functional status. The aim of this case series is to examine outcomes of operative versus nonoperative management of femur fractures in this patient population.Methods: An IRB-approved retrospective chart review was completed for patients with DMD treated at a single institution for a femur fracture between 2013-2022. Patients were excluded for incomplete documentation, treatment initiation at an outside hospital, or diagnosis of a different muscular dystrophy. Demographic variables, treatment information, functional status, and adverse events were collected for each patient. Descriptive statistics were used to summarize demographic and outcome variables.Results: A total of 10 patients with 11 femur fractures were included for analysis. All patients were male with an average age of 12.7 years and clinical follow-up of 286 days. Five fractures in five patients underwent operative fixation (Group A), and six fractures in five patients underwent nonoperative management (Group B). In Group A, three patients were short-distance ambulators prior to injury, and all patients regained a similar functional status postoperatively. All three patients were treated with a locked intramedullary nail. One patient in Group B was a short-distance ambulator prior to injury; the remainder were nonambulatory. All patients in Group B were primary wheelchair users at final follow-up. There were no adverse events as a result of treatment in either group.Conclusion: Nonoperative management with cast immobilization remains an acceptable option for nonambulatory patients and those with minimally displaced fractures not amenable to surgical intervention. Surgical intervention is recommended for higher-functioning patients with the goal of restoring ambulatory status. Regardless of treatment modality, patients should receive aggressive physical therapy directed at early weight-bearing, range of motion, and mobilization to preserve strength, muscle mass, and mobility.Level of Evidence: Level IV case series Key Concepts•Management of femur fractures in Duchenne muscular dystrophy should account for fracture morphology as well as patient functional status.•Surgical management is safe and effective in promoting fracture union and preserving functional status.•Nonoperative management is preferred in nonambulatory patients and for minimally displaced fractures.