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.

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.

Dystrophin Expressing Chimeric (DEC) Cell Therapy for Duchenne Muscular Dystrophy: A First-in-Human Study with Minimum 6 Months Follow-up.

Duchenne Muscular Dystrophy (DMD) is a X-linked progressive lethal muscle wasting disease for which there is no cure. We present first-in-human study assessing safety and efficacy of novel Dystrophin Expressing Chimeric (DEC) cell therapy created by fusion of patient myoblasts with myoblasts of normal donor origin. We report here on safety and functional outcomes of the first 3 DMD patients. No study related adverse events (AE) and no serious adverse events (SAE) were observed up to 14 months after systemic-intraosseous administration of DEC01. Ambulatory patients showed improvements in functional tests (6-Minute Walk Test (6MWT), North Star Ambulatory Assessment (NSAA)) and both, ambulatory and non-ambulatory in PUL, strength and fatigue resistance which correlated with improvement of Electromyography (EMG) parameters. DEC01 therapy does not require immunosuppression, involves no risks of off target mutations, is not dependent upon the causative mutation and is therefore a universal therapy that does not use viral vectors and therefore can be readministered, if needed. This study was approved by the Bioethics Committee (approval No. 46/2019). Mechanism of action of the Dystrophin Expressing Chimeric Cell (DEC) cells created via ex vivo fusion of human myoblast from normal and DMD-affected donors. Following systemic-intraosseous administration, DEC engraft and fuse with the myoblasts of DMD patients, deliver dystrophin and improve muscle strength and function. (Created with BioRender.com).

Characteristics of Selected Somatic and Motor Abilities of Youth Soccer Players with Diabetes Type 1 Treated with Insulin Pump Therapy.

Long-term insulin treatment can slow the growth process and decrease physical fitness level in children. In diabetic children, these two developments should be constantly monitored. The aim of the present study was to examine differences in somatic and physical fitness characteristics between soccer-training boys with type 1 diabetes and healthy boys of the same age (reference values based on Polish population norms for somatic and motor parameters). The participants were 94 boys (8-17 years), diagnosed with diabetes, who participated in soccer training on a regular basis and received routine medical care. The study involved (a) anthropometric and body composition measurements, (b) general motor ability assessments, and (c) comparison of those characteristics with the healthy Polish population. The diabetic boys were found to have lower levels of almost all somatic traits and motor abilities as compared with the healthy boys (p ≤ 0.05). Handgrip strength was a variable with the smallest difference between the two groups. The observed differences indicate the necessity to design an appropriate control and assessment system based on simple medical and fitness field tests for diabetic children and adolescents. It will allow optimizing advanced training as well as minimize health risks before, during, or after exercise.

Assessment of changes in blood lactate levels in children and adolescents with type 1 diabetes during a football tournament (GoalDiab Study).

INTRODUCTION: Monitoring physical activity is a very important issue, especially in type 1 diabetes. One of the parameters assessing the intensity of exercise is the concentration of lactate in the blood. Aim of the study We assessed the intensity of PE and changes in lactate levels in children and adolescents with type 1 diabetes (T1D) during a football tournament. MATERIAL AND METHODS: We enrolled 141 participants, the results of 70 of whom were analyzed, playing in two age categories: 10-13 and 14-17 years. Lactate levels were measured in the capillary blood before and after matches. Blood lactate of 4 mmol/l (Onset Blood Lactate Accumulation OBLA) was used as parameter indicating the prevalence of anaerobic metabolic changes. RESULTS: The median lactate level was 1.8 mmol/l before and 4.4 mmol/l after matches (p < 0.001). The increase in lactate levels was higher in the older age category (4.3 vs. 1.8, p = 0.001) and was independent on gender (3.2 vs. 2.1, p = 0.597), personal insulin pump vs insulin pen use (3.0 vs. 1.5, p = 0.145) or training in a sports club (1.4 vs. 3.0, p = 0.084). A positive correlation was noted between increased lactate levels and age (Rs = 0.253, p = 0.034). 61% of the participants exceeded lactate levels ≥ 4 mmol/l. In univariate logistic regression analysis age was a significantly associated with lactate level ≥ 4 mmol/l [OR = 1.45 (1.08-1.95)] independent of HbA1c, gender, treatment method and training in a sports club. CONCLUSIONS: PE intensity levels during football matches were found to be mixed aerobic-anaerobic. Increases in lactate levels were greater in the older subjects independently on the assessed factors.

Nighttime Hypoglycemia in Children with Type 1 Diabetes after one Day of Football Tournament.

The aim of the study was to investigate factors related to the occurrence of nighttime hypoglycemia after a football tournament in children with type 1 diabetes mellitus. The multicenter study (GoalDiab study) included 189 children and adolescents with type 1 diabetes mellitus, from 11 diabetes care centers in Poland. Hypoglycemia was defined according to the International Hypoglycemia Study Group Statement. We analyzed the data of 95 participants with completed protocols with regards to nighttime hypoglycemia (82% male), aged 11.6 (9.8-14.2) years, diabetes duration 5.0 (2.0-8.0) years. There were 47 episodes of nighttime Level 1 hypoglycemia (≤3.9 mmol/L). Occurrence of clinically important Level 2 hypoglycemia (<3.0 mmol/L) during a game period was positively associated with nighttime hypoglycemia (≤3.9 mmol/L) incident (Odds Ratio=10.7; 95% Confidence Interval: 1.1-100.2; p=0.04). Using Continuous Glucose Monitoring was negatively associated with the occurrence of nighttime hypoglycemia (≤3.9 mmol/L) compared with using glucose meters or Flash Glucose Monitoring (Odds Ratio=0.31; 95% Confidence Interval: 0.12-0.83; p=0.02). The occurrence of clinically important hypoglycemia related to physical activity is associated with the occurrence of hypoglycemia during the night. Continuous Glucose Monitoring is negatively associated with nighttime hypoglycemia after a day of competition.

Assessment of Safety and Glycemic Control During Football Tournament in Children and Adolescents With Type 1 Diabetes-Results of GoalDiab Study.

PURPOSE: To assess glycemic control and safety of children and adolescents with type 1 diabetes participating in a 2-day football tournament. METHODS: In total, 189 children with type 1 diabetes from 11 diabetes care centers, in Poland, participated in a football tournament in 3 age categories: 7-9 (21.2%), 10-13 (42.9%), and 14-17 (36%) years. Participants were qualified and organized in 23 football teams, played 4 to 6 matches of 30 minutes, and were supervised by a medical team. Data on insulin dose and glycemia were downloaded from personal pumps, glucose meters, continuous glucose monitoring, and flash glucose monitoring systems. RESULTS: The median level of blood glucose before the matches was 6.78 (4.89-9.39) mmol/L, and after the matches, it was 7.39 (5.5-9.87) mmol/L (P = .001). There were no episodes of severe hypoglycemia or ketoacidosis. The number of episodes of low glucose value (blood glucose ≤3.9 mmol/L) was higher during the tournament versus 30 days before: 1.2 (0-1.5) versus 0.7 (0.3-1.1) event/person/day, P < .001. Lactate levels increased during the matches (2.2 [1.6-4.0] mmol/L to 4.4 [2.6-8.5] mmol/L after the matches, P < .001). CONCLUSIONS: Large football tournaments can be organized safely for children with type 1 diabetes. For the majority of children, moderate mixed aerobic-anaerobic effort did not adversely affect glycemic results and metabolic safety.

Transient lesion in the splenium of the corpus callosum due to rotavirus infection.

Transient signal changes in magnetic resonance imaging (MRI) of the splenium of the corpus callosum (SCC) can result from many different reasons, including encephalitis and encephalopathy caused by infection, seizures, metabolic disorders and asphyxia. We report a case of a 6-year-old Polish girl with rotavirus infection demonstrating a reversible SCC lesion on diffusion-weighted MRI images. She presented six episodes of generalized tonic seizures with mild acute gastroenteritis. Stool test for rotavirus antigen was positive. At the time of admission imaging showed the hyperintense region in T2-weighted and fluid-attenuated inversion-recovery MRI, a well-defined lesion in the splenium of the corpus callosum with restricted diffusion in diffusion-weighted MRI and no enhancement in post contrast T1-weighted imaging. Her first EEG showed slow brain activity in the posterior occipitotemporal portion, consisting mainly of theta waves with a frequency of 4.5-5.5 Hz and amplitude of 40 uV. The lesion had completely disappeared on follow-up MRI 10 days later. The patient recovered fully without any sequelae.

[Effects of massage on delayed-onset muscle soreness]. / Wplyw masazu na powysilkowa bolesnosc miesni.

INTRODUCTION: Delayed onset muscle soreness (DOMS) is the pain or discomfort often felt 12 to 24 hours after exercising and subsides generally within 4 to 6 days. Once thought to be caused by lactic acid buildup, a more recent theory is that it is caused by inflammatory process or tiny tears in the muscle fibers caused by eccentric contraction, or unaccustomed training levels. Exercises that involve many eccentric contractions will result in the most severe DOMS. MATERIAL AND METHODS: Fourteen healthy men with no history of upper arm injury and no experience in resistance training were recruited. The mean age, height, and mass of the subjects were 22.8 +/- 1.2 years, 178.3 +/- 10.3 cm, and 75.0 +/- 14.2 kg, respectively. Subjects performed 8 sets of concentric and eccentric actions of the elbow flexors with each arm according to Stay protocol. One arm received 10 minutes of massage 30 minutes after exercise, the contralateral arm received no treatment. Measurements were taken at 9 assessment times: pre-exercise and postexercise at 10 min, 6, 12, 24, 36, 48, 72 and 96 hours. Dependent variables were range of motion, perceived soreness and upper arm circumference. RESULTS: There was noticed difference in perceived soreness across time between groups. The analysis indicated that massage resulted in a 10% to 20% decrease in the severity of soreness, but the differences were not significant. Difference in range of motion and arm circumference was not observed. CONCLUSIONS: Massage administered 30 minutes after exercises could have a beneficial influence on DOMS but without influence on muscle swelling and range of motion.