An alternative mechanism for skeletal muscle dysfunction in long-term post-viral lung disease.

Chronic lung disease is often accompanied by disabling extrapulmonary symptoms, notably skeletal muscle dysfunction and atrophy. Moreover, the severity of respiratory symptoms correlates with decreased muscle mass and in turn lowered physical activity and survival rates. Previous models of muscle atrophy in chronic lung disease often modeled chronic obstructive pulmonary disease (COPD) and relied on cigarette smoke exposure and LPS stimulation, but these conditions independently affect skeletal muscle even without accompanying lung disease. Moreover, there is an emerging and pressing need to understand the extrapulmonary manifestations of long-term post-viral lung disease (PVLD) as found in COVID-19. Here, we examine the development of skeletal muscle dysfunction in the setting of chronic pulmonary disease caused by infection due to the natural pathogen Sendai virus using a mouse model of PVLD. We identify a significant decrease in myofiber size when PVLD is maximal at 49 days after infection. We find no change in the relative types of myofibers, but the greatest decrease in fiber size is localized to fast-twitch-type IIB myofibers based on myosin heavy chain immunostaining. Remarkably, all biomarkers of myocyte protein synthesis and degradation (total RNA, ribosomal abundance, and ubiquitin-proteasome expression) were stable throughout the acute infectious illness and chronic post-viral disease process. Together, the results demonstrate a distinct pattern of skeletal muscle dysfunction in a mouse model of long-term PVLD. The findings thereby provide new insights into prolonged limitations in exercise capacity in patients with chronic lung disease after viral infections and perhaps other types of lung injury.NEW & NOTEWORTHY Our study used a mouse model of post-viral lung disease to study the impact of chronic lung disease on skeletal muscle. The model reveals a decrease in myofiber size that is selective for specific types of myofibers and an alternative mechanism for muscle atrophy that might be independent of the usual markers of protein synthesis and degradation. The findings provide a basis for new therapeutic strategies to correct skeletal muscle dysfunction in chronic respiratory disease.

Po251 / #854 Noninvasive Closed Loop Diaphragm Stimulation for Ventilated Icu Patients: E-Poster Viewing

Introduction: Many COVID-19 patients need prolonged artificial ventilation. Skeletal muscle wastes rapidly when deprived of neural activation, and in ventilated patients the diaphragm muscle begins to atrophy within 24 hours (ventilator induced diaphragmatic dysfunction, VIDD). This profoundly weakens the diaphragm, complicating the weaning of the patient off the ventilator, and increasing the risk of complications such as bacterial pneumonia. 40% of the total duration of mechanical ventilation in ITU patients is accounted for by the weaning period, after the initial illness has resolved. Prevention of VIDD would therefore both improve individual outcomes, and also release ITU capacity. We aim to prevent VIDD by exercising the diaphragm with electrical stimulation of the nerves that control it. Evidence suggests that muscle wasting can be prevented by quite low levels of exercise (e.g. 200 contractions per day). Materials / Methods: The diaphragm is activated by the phrenic nerves, formed from branches of the C3-C5 nerve roots in the neck. These nerves may be electrically stimulated in the lower neck. An electrode array is positioned on each side of the neck using surface landmarks. The system automatically determines the best electrode to use in each array. Sensors built into the ventilatory circuit are monitored both to match stimulation to the respiratory cycle and to determine the effects of stimulation. Result(s): We have designed and built a prototype system for unsupervised noninvasive phrenic nerve stimulation. The system delivers one contraction every 7 minutes, synchronised to early inspiration so as not to disrupt ventilation. Electrode impedances are measured before each stimulus, and the closed loop system continuously monitors the effects of stimulation on airflow and adjusts stimulation parameters to compensate for changes in coupling, for example due to head movement. Discussion(s): This stimulator system overcomes several limitations of existing solutions, namely the resource implications and risk profile of invasive electrodes, and the requirement for supervised operation. While invasive systems are applied selectively for these reasons, routine use of our system can be envisaged. This system was inspired by COVID-19 patients but is not limited to them, and has broad applicability to ventilated intensive care patients in general, for example patients with traumatic brain injury. Conclusion(s): Non-invasive stimulation of the phrenic nerves using pressure-free skin surface electrodes is feasible and safe. It offers the potential for prevention of VIDD and thereby faster ventilator weaning and shorter stay on ITU. Clinical trials are planned in 2022. Learning Objectives: After this presentation delegates should be aware of: 1. Ventilation induced diaphragm dysfunction (VIDD) and its importance in patients having lengthy periods of ventilation, as in many cases of COVID-19. 2. The fact that low levels of activity can maintain the condition of skeletal muscles including the diaphragm muscle 3. The potential for noninvasive stimulation of the phrenic nerves to provide 'diaphragm exercise' and prevent VIDD. Keywords: phrenic nerve stimulation, diaphragm, ventilation, COVID-19Copyright © 2022

Effects of Telerehabilitation on Patients with Severe Haemophilia A: A Single Center Experience

Introduction: The importance of movement iswidely confirmed in people with haemophilia. After the spread of SARS-CoV-2, though, and the subsequent pandemic and lockdown, several haemophilia centres started providing physiotherapy via tele medicine. The role of telerehabilitation in haemophilia patients remains unclear. We, therefore, studied the impact of a physiotherapy course with group sessions via Zoom platform (Zoom Video Communications, Inc.) on a group of severe haemophilia A patients. Method(s): We included patients with severe haemophilia A, who were undergoing prophylaxis with clotting factor concentrates or emicizumab and with at least one target joint;an exclusion criterion was a therapeutic switch during the year. A complete assessment of the patients was performed using the Hemophilia Joint Health Score (HJHS) and the quality-of-life questionnaire EQ-5D-5L before starting the physiotherapy course (T0) and at the end of the one-year-course (T1). During the course year, one exercise session per week was planned, led by a physiotherapist, and corrected by an observer physiotherapist. During the session, warm-up, global muscle strengthening, stretching, proprioception and coordination exercises were carried out. Result(s):We recruited 10 patients aged 29-54 years (mean: 42.6;standard deviation: 9.607). In this group, only two were already doing sports once a week - swim and nordic walking. Only one patient required additional treatment due to a post-fall hematoma on amountain hike. The mean HJHS was 10.8 at T0, decreased to 9.6 at T1. The HJHS-specific items relating to pain, muscle strength and muscle atrophy had all improved, while the parameters relating to joint damage were understandably unchanged. All the patients reported a feeling of well-being at the end of the course, and the mean of the global EQ-5D-5L score in T0 was 81, while at T1 was 85. Discussion/Conclusion: This experience highlights the role of telerehabilitation, an innovative tool that can give access to physical exercise to patients otherwise limited by the geographical distance or by the impossibility of reaching the treatment sites. However, further large studies are needed to fully explore its potential.

Acute motor and sensory axonal neuropathy in a patient with undiagnosed mixed connective tissue disease

Case Report: Acute motor and sensory axonal neuropathy (AMSAN) syndrome is a rare subtype of Guillain-Barre syndrome (GBS) with poor recovery [1]. While respiratory and gastrointestinal infections may precipitate AMSAN, an underlying autoimmune disorder is seldom reported in literature. We herein report the complex case of a patient with undiagnosed, asymptomatic mixed connective tissue disease (MCTD) who developed AMSAN syndrome. Case: A 44-year-old Asian male without medical history presented with progressively worsening weakness of both upper and lower extremities and inability to perform daily activities. His symptoms started 12 weeks prior with difficulty standing from a seated position. He felt subjectively better for some time until a week prior, when he became bedbound. He had diarrhea 6 months ago, with 5-6 loose bowel movements a day for a few weeks. Vital signs on admission was normal. On neurological examination, he was alert and oriented, with bilateral upper and lower extremity flaccid paralysis, diffuse muscle atrophy, bilateral hand and foot drop, negative Hoover sign, diffuse areflexia, and intact sensation. Cerebrospinal fluid (CSF) analysis showed WBC 0 and protein level 136. MRI cervical, thoracic, and lumbar spine were normal. EMG revealed sensory involvement with positive sharp waves in proximal muscles along with fibrillations. Intravenous immunoglobulin (IVIG) was initiated at 0.4 mg/kg for 5 days. Infectious workup for COVID-19, stool culture, HIV, TB, RPR and campylobacter jejuni antibody (Ab), was negative. ANA was positive in a speckled pattern with titres 1:1280, with a positive RNP Ab, SS-A, and RF IgM, IgG and IgA. Rest of the autoimmune workup (anti-dsDNA, anti-CCP, SS-B, aldolase, anti-Jo-1, anti-Scl-70, p-ANCA, c-ANCA, anti-GM1, anti-GQ1b, and anti-GD1a ganglioside Ab) was negative. The myositis specific 11 Ab panel was negative. Despite IVIG therapy, he developed dysphagia, respiratory distress, with a negative inspiratory force of -0, requiring intubation. He had a tracheostomy and PEG tube placed and remains quadraplegic nearly 120 days later. Discussion(s): The authors report a unique case of a patient who became progressively weak over 3 months, leading to complete quadriplegia. Interestingly, this is more consistent with chronic inflammatory demyelinating poly-neuropathy (CIDP), as AMSAN typically develops over a short period of 2 to 4 weeks [2]. Despite having negative anti-GM1 and anti-GD1a Ab (in which positive Ab are pathognomonic but not always present in AMSAN syndrome), the patient had weakness that began in the lower extremities, progressing to paralysis, along with albuminocytological dissociation on CSF analysis, pointing to a GBS diagnosis [3]. He had sensory involvement in the EMG, thus making the diagnosis as AMSAN. He had an undiagnosed, asymptomatic autoimmune process most consistent with MCTD. Whether the two disease processes are related to each other is a concept that has not yet been investigated. Pediatric Clinical Case Reports Concurrent Session Saturday February 4, 2023 1:00 PM Copyright © 2023 Southern Society for Clinical Investigation.

Steroids - Exploitation

Corticosteroids, more specifically glucocorticoids are one of the most prescribed drugs. Corticosteroids are adrenal hormones that serve significant physiologic activities such as modulating glucose metabolism, protein catabolism, calcium metabolism, bone turnover control, immunosuppression, and down-regulation of inflammatory cascade. Corticosteroids are regarded life-saving due to their various effects and have been used therapeutically to treat broad range of auto-immune, rheumatologic, inflammatory, neoplastic, and viral illnesses.However, the therapeutic benefits of glucocorticoids are restricted by the adverse effects. The most serious side effects of corticosteroids are associated with the use of higher doses for longer periods and OTC availability in specific pharmacies, which leads to dependency, as well as its usage in mild and moderate server instances, which is contrary to guidelines. In the recent times the use of corticosteroids has been multiplied with the emergence of the Covid -19 pandemic. WHO and the standard guidelines has recommended the usage of corticosteroids in critically ill covid-19 patients but their usage in mild and moderate cases caused more harm than benefit. This illicit usage has resulted in the development of opportunistic fungal illnesses such as mucormycosis, posing an extra risk to patients in terms of quality of life and finances. Other adverse effects of systemic corticosteroids include morphological changes, increased blood sugar levels, delayed wound healing, infections, decreased bone density, truncal obesity, cataracts, glaucoma, blood pressure abnormalities, and muscle fibre atrophy.In this review we want to discuss the significance and detrimental effects of corticosteroids emphasizing on the recent times i.e., COVID-19.

A paralysis poser: a growing COVID concern

Purpose of Study: Report a rare case of onset of seronegative, juvenile dermatomyositis likely potentiated by Covid-19 infection Methods Used: Case analysis and literature research Summary of Results: A 7 year-old previously healthy male presented with 3 weeks of progressive, bilateral upper and lower extremity weakness, difficulty swallowing, voice changes, periorbital edema, and rash. Recent history was notable for diagnoses of COVID-19 one month prior to presentation and streptococcal pharyngitis 2 months prior to presentation. Notably, there is a family history of systemic lupus erythematosus. On examination, the patient demonstrated bilateral periorbital swelling with purple discoloration of the upper eyelids, a violaceous, pruritic, macular rash on his upper extremities and on his abdomen. Musculoskeletal exam was significant for severe axial (strength 2/5) and proximal (strength 3/5) muscleweakness with notable inability to sit unsupported or maintain head control. His neurologic exam was nonfocal;however, diffuse hyporeflexia in both upper and lower extremities were elicited. Initial screening labs were notable for mild transaminitis;positive ANA (1:80 in speckled pattern), negative ANCA, negative dsDNA/Anti- Sm, elevated aldolase of 10.3, CK 464, and LDH 665;normal thyroid studies and normal inflammatory markers. MRI with and without contrast of the spine indicated diffuse myositis of all muscle groups. Due to concern for autoimmune mediated myositis, Rheumatology was involved early in the patient's course. Empiric treatment was initiated early in the patient's presentation with IVIG, steroids, methotrexate, and plaquenil leading to gradual improvement in symptoms. Subsequent muscle biopsy was consistent with juvenile dermatomyositis (JDM). Conclusion(s): JDM is rare, occurring in 1 to 15 per million children. It classically presents with proximal myopathy and dermatologic findings of Gattron's papules, a heliotrope and malar rash. Its pathophysiology is not yet well defined but is thought to be a humoral mediated autoimmune disease. Muscle biopsies characteristically show perifascicular and perivascular infiltration. Early diagnosis and treatment with steroids, immune modulators, and physical therapy is critical to limit muscle atrophy. Viral infections are known triggers of rheumatologic diseases broadly;however, the more pronounced type 1 interferon response associated with COVID-19, which is known to be a driving pathway of JDM, may be a risk factor for severe, recalcitrant disease. Future research is needed to better identify involved pathophysiology and target future treatment efforts. Additionally, more education and case reports could focus on dermatologic presentations of individuals with pigmented skin. Copyright © 2023 Southern Society for Clinical Investigation.

CASE REPORT of A HARD to TREAT DERMATOMYOSITIS after A COVID-19 INFECTION and SUBSEQUENT VACCINATION

Background: A 50 years old woman, a medical doctor, came to our department with symmetrical proximal muscular weakness, several months after Covid-19 infection and three weeks after a second dose of Covid-19 mRNA vaccine. The patient had no prior or family history of autoimmune diseases and take no medicines. In the past she undergone an operation for double-kidney with frequent urinary infections. Objective fndings have shown symmetrical proximal muscular weakness and classic sings of dermatomyositis-Gottron's papules, shawl and holster signs, periungual vasculitis. Objectives: We present a case of a 50 old woman with clinical and laboratory proven dermatomyositis, starting three weeks after a second dose of a Covid1-19 mRNA vaccine without other reasons. Methods: The laboratory tests showed elevated CPK, lactate dehydroge-nase, aspartate aminotransferase and alanine aminotransferase, high ANA-1:1280 and myositis specifc autoantibodies-anti-NXP2 and anti-Mi-2-beta. The electromyography showed myopathic changes and the muscle MRI-symmetrical edema of mm.obturator and mm.adductor brevis. We exclude diseases that may mimic infammatory myopathies. We made a cancer screening-whole body MRI, colonoscopy, gastroscopy, mammography and gynecological exam, immunoblot for detection of paraneoplastic syndrome-associated neuronal antibodies, with no detection of cancer. Muscle biopsy of m.vastus lateralis showed attenuating muscle infammation with advancing muscle atrophy and fbrosis. Results: The diagnose dermatomyositis was made according Bohan and Peter criteria and we start a high dose (1mg/kg/day) glucocorticoid therapy with good initial clinical and laboratory effect. Two months after starting a therapy muscle weakness worsened together with difficulty of swallowing. We excluded steroid myopathy after second EMG and lack of improvement when tapering the GS dose. Methotrexate 20 mg/weekly was added as a steroid sparing drug with good response, but was stopped because fare of pyelonephritis. Accordning to the opinion of dermatologist hydroxychloroquine was started for a couple of weeks, because of active skin manifestations. Muscle weakness worsened on the background of treatment, which was stopped. We started a therapy with intravenous immunoglobulins and considered therapy with cyclophosphamide or azathio-prine after urinary infection. Because the patient was infected for a second time with covid-19, although vaccine, we continued only with glucocorticoids and anti-osteoporotic therapy. Conclusion: The etiology and pathogenesis of infammatory myopathies are not fully clarifed so far. We speculate that the infection with Covid-19 as well as mRNA vaccine trigger infammatory myopathy and compromise the patient's immunity for poor treatment response with glucocorticoids and immunosuppres-sives. On the other hand advanced muscle atrophy and fbrosis within a short period show that suspected triggering factors could be a reason for difficult to treat such type of dermatomyiositis.

WHY YOU SHOULDN'T AIM TOO HIGH ALL THE TIME: A CASE OF SHOULDER INJURY RELATED TO VACCINE ADMINISTRATION (SIRVA) OF COVID-19 MRNA

CASE: A 23-year-old female presented to resident clinic for 7 months of right shoulder pain. She received her second COVID-19 mRNA vaccine just prior to onset of pain. She noted vaccine administration was “traumatic” with significant bleeding and bruising. She started noticing pain with overhead activities several days later. She is very active with cardiovascular exercises. She lifts weights but none requiring overhead motions. The pain was worst at the front of the shoulder but radiated to the lateral aspect. She had not tried, ice, heat, medications or physical therapy. Because of her injury, she was hesitant to receive her COVID-19 booster. BMI was low at 16.65. Exam showed thin build and overall low muscle bulk. Right shoulder showed no signs of muscle atrophy. There was tenderness of subacromial and coracoid areas. No pain along biceps tendon or AC joint. She had full ROM with shoulder abduction, internal and external rotation. She had full strength of supraspinatus, infraspinatus, teres minor, and subscapularis muscles. She noted pain with abduction, internal rotation and lift-off maneuver. Her Hawkins and Neer's maneuvers were positive. No pain with Yergason's and Speed's maneuvers. The patient was diagnosed with right shoulder subacromial bursitis and impingement syndrome. IMPACT/DISCUSSION: Mild shoulder pain is expected after vaccine administration and typically resolves in days. However, SIRVA is an increasingly recognized complication of improper vaccine administration particularly in the occupational setting. SIRVA results from vaccine being delivered inadvertently within the subdeltoid bursa or joint space. It is thought to result from an immune mediated reaction to the vaccine components as injury tends to be greater than expected from a needle injury. We were able to find 5 cases of reported SIRVA related to the COVID vaccine. All included some form of subacromial, subdeltoid, or subcoracoid bursitis. One case noted a supraspinatus tear. Ultrasound has demonstrated the subacromial bursa can extend distal to the acromion by up to 6 cm, so administration to bursa is possible in the superior deltoid. Appropriate injection technique can reduce the risk of injury;administrators should use landmarks of the acromion and distal insertion point of deltoid mid-humerus. Proper needle length is important. It has been suggested a smaller deltoid fat pat and smaller deltoid muscle bulk are risk factors for SIRVA. Women tend to have a higher incidence. CONCLUSION: We presented the case of a slender female who developed shoulder bursitis and impingement following administration of COVID-19 mRNA vaccine. She was referred to PT for rotator cuff strengthening, instructed to refrain from aggravating activities, and provided NSAIDs for pain relief. She reports pain relief. Another option for a more severe case would be a subacromial bursa steroid injection. It is important for providers to be aware of this pathology to provide appropriate treatment and decrease vaccine hesitancy.

The Functional Role of Long Non-Coding RNA in Myogenesis and Skeletal Muscle Atrophy.

Skeletal muscle is a pivotal organ in humans that maintains locomotion and homeostasis. Muscle atrophy caused by sarcopenia and cachexia, which results in reduced muscle mass and impaired skeletal muscle function, is a serious health condition that decreases life longevity in humans. Recent studies have revealed the molecular mechanisms by which long non-coding RNAs (lncRNAs) regulate skeletal muscle mass and function through transcriptional regulation, fiber-type switching, and skeletal muscle cell proliferation. In addition, lncRNAs function as natural inhibitors of microRNAs and induce muscle hypertrophy or atrophy. Intriguingly, muscle atrophy modifies the expression of thousands of lncRNAs. Therefore, although their exact functions have not yet been fully elucidated, various novel lncRNAs associated with muscle atrophy have been identified. Here, we comprehensively review recent knowledge on the regulatory roles of lncRNAs in skeletal muscle atrophy. In addition, we discuss the issues and possibilities of targeting lncRNAs as a treatment for skeletal muscle atrophy and muscle wasting disorders in humans.

Clinicohaematological Patterns of Anemia and Correlation with Clinical Conditions in Children Aged 5 to 12 Years in Tertiary Care Centre

Objective: To classify the haematological pattern, severity of anemia in children 5-12 years age admitted and to find its correlation with the clinical conditions. Methods Crossectional study of 160 patients in two years was done. Patients satisfying the inclusion criteria were selected for study. Relevant clinical data were recorded in a structured proforma including detailed history was recorded with particular symptoms suggestive of anemia such as weakness and easily fatigability, breathlessness on exertion and pica. A thorough clinical examination of every child was done followed by routine investigations for anemia Results Patients between 7-8 year were found to be the most affected. Anemia was found to be more common in female children as compared to male children (F:M=1.13). Anemia is more common in undernourished child. Most common presenting symptoms were gastrointestinal including vomiting, diarrhea and pain abdomen. Most common sign was Pallor followed by other common signs included signs of dehydration associated with diarrhea, hepatosplenomegaly. microcytic hypochromic anemia was the most common morphological type of anemia and macrocytic anemia was the least common.Thalassemia cases were most common among hemolytic anemias. Iron Deficiency Anemia (Nutritional Anemia) was the most common etiology of anemia. Conclusion Dietary deficits affect children aged 5 to 12, creating financial, emotional, and psychological burden for patients and their families, as well as depleting critical national resources. As a result, screening for these illnesses, as well as early detection of anemia and related problems, is essential.

The Role of Oxidative Stress in Skeletal Muscle Myogenesis and Muscle Disease.

The contractile activity, high oxygen consumption and metabolic rate of skeletal muscle cause it to continuously produce moderate levels of oxidant species, such as reactive oxygen species (ROS) and reactive nitrogen species (RNS). Under normal physiological conditions, there is a dynamic balance between the production and elimination of ROS/RNS. However, when the oxidation products exceed the antioxidant defense capacity, the body enters a state of oxidative stress. Myogenesis is an important process to maintain muscle homeostasis and the physiological function of skeletal muscle. Accumulating evidence suggests that oxidative stress plays a key role in myogenesis and skeletal muscle physiology and pathology. In this review, we summarize the sources of reactive oxygen species in skeletal muscle and the causes of oxidative stress and analyze the key role of oxidative stress in myogenesis. Then, we discuss the relationship between oxidative stress and muscle homeostasis and physiopathology. This work systematically summarizes the role of oxidative stress in myogenesis and muscle diseases and provides targets for subsequent antioxidant therapy and repair of inflammatory damage in noninflammatory muscle diseases.

Long Covid: what is already known about this new condition?

Long COVID affects people who have experienced a severe form of COVID-19, as well as patients who suffered a mild form. Six months after infection with the coronavirus, at least 1 out of 7 patients still have symptoms. These symptoms are very diverse and are probably related to a combination of different mechanisms: direct organ damage due to the viral infection, abnormal immune and inflammatory responses that can lead to dysfunctions on several levels (microcirculation, coagulation, fibrosis, autoimmunity, metabolism), consequences of the hospitalisation (muscle atrophy, post-intensive care syndrome) or worsening of existing comorbidities. The Belgian Healthcare Knowledge Centre (KCE) surveyed the experience of Belgian patients by means of an extensive online survey of 1,320 people, followed by an online forum and in-depth interviews. It showed that the perception of the symptoms was very diverse, with a clear reduction in the quality of life, some loss of autonomy and difficulties when returning to work. The psychological consequences could be severe. Based on the current state of science, it is not known which treatments are effective for long COVID. A symptom-oriented approach, focused on gradual multidisciplinary rehabilitation, seems appropriate. Therefore, the main recommendation of the KCE is to investigate the possibility of introducing an 'interdisciplinary bilan' for patients with different and interrelated complaints.

Return to exercise after covid-19 disease

Objectives: Physical activity is one of most important parts of a healthy life style. After COVID-19 we have to consider alterations needed in prescribing exercise. Methods: A comprehensive review. Results: The guidelines for returning to exercise should consider elite athletes as well as the general population in two different categories. We may also classify the patients to these categories: 1. Those who were not affected by COVID-19 or were completely asymptomatic and were home-quarantined;this group will suffer from deconditioning. They have to begin milder physical activity and reduced duration compared to the previous active days before quarantine. The increase in volume and severity of exercises are based on the general condition and the patient's tolerance. All major changes should be monitored by a medical profession expert. 2. Those who were affected by mild to moderate COVID-19 and were not hospitalized;this group will suffer from decreased cardio-respiratory fitness as well as deconditioning. They have to begin with semi-monitored activities. Oxygen saturation should be monitored during physical activity and supplemental oxygen may improve tolerance and safety. 3. Those who were affected by severe COVID-19 and were hospitalized;this group will suffer from severe generalized muscle wasting and decreased cardiorespiratory fitness. They have to begin with in-patient rehabilitation. All participants have to pay attention to social/physical distancing and good hygienic measures, proper warm-up/cool down, adequate hydration, and appropriate dietary regimen. Many affected patients may need protein supplements to counteract severe muscle wasting;anti-oxidant and vitaminmineral supplements may be helpful because of long term decreased intake during hospitalization (low appetite, intensive care measures, and gastrointestinal symptoms). Psychological consultation to manage posttraumatic stress disorder, anxiety, depression, obsessive symptoms should not be neglected.

ASSESSING the IMPACT of COVID-19 on PEOPLE with HEMOPHILIA (PWH) AGED ≥40 YEARS and the HTCS THAT CARE for THEM: AN OBSERVATIONAL COHORT STUDY from the ADVANCE WORKING GROUP

Introduction: ADVANCE provides a unique opportunity to compare the rates of infection and outcomes in PWH with the corresponding non-hemophilia populations, to identify any specific issues relating to COVID-19 infection in older PWH and provide guidance on the management of COVID-19 for the broader hemophilia community. Methods: A retrospective and prospective observational cohort study of 3,851 PWH (A/B aged ≥ 40 years registered at 18 ADVANCE Hemophilia Treatment Centers (HTCs) comprising a snapshot (Survey 1A) and a detailed follow-up (Survey 1B) to provide information on patients confirmed with COVID-19 infection from March to November 2020. Results: At the time of data submission, 5 HTCs reported being in their second wave, 12 in national/regional lockdown during a second wave and one center was in their third wave. In the 14 HTCs that completed Survey 1B, there were 26 confirmed COVID-19 cases in PWH aged ≥40 at 8 HTCs, ranging from 0.1-4.3% of the total PWH population at each center: 23 with HA (19 severe) and 3 with severe HB. Diagnosis was confirmed via a PCR test in 13 patients and 13 by nasal swab alone. At diagnosis, 7 patients were aged ≥40 years;9 were ≥50 years, 7 were ≥60 years;2 were ≥70 years;and 1 was ≥80 years. Of the 26 confirmed cases, 7 were hospitalized (2 in the ICU), 1 patient died and 3 have been discharged with ongoing COVID-19-related problems. No patients reported any increase in bleed symptoms. The majority (18/26) of confirmed cases did not have a condition known to increase the risk of severe illness from COVID-19;however, 7 were obese and 4 had diabetes (1 had both). Half the patients had hypertension, which was suggested to put people at increased risk of severe illness from COVID-19. Eight centers reported a negative impact on comorbidity management due to postponement of elective surgeries and specialist appointments, and reduced physical activity leading to muscle atrophy and reduced range of motion. Discussion/Conclusion: Although direct comparisons with the general population are complex and currently unavailable for age groups, it is reassuring that the number of PWH with confirmed COVID-19 is lower or similar to that of the general population (ranging from 5% in Germany to 14% in Slovenia). Further data from this ongoing study will add to our understanding of the impact of COVID-19 in older PWH.

Interval training in the treatment of chronic effects of COVID-19

BACKGROUND AND PURPOSE: The World Health Organization categorized COVID-19 as a pandemic on March 11th, 2020. Since then, maximizing survival of those infected has been the major focus of many health services. Those who suffered from the virus are now experiencing ongoing symptoms that may last several months or more. These symptoms can include fatigue, pain, muscle atrophy, weakness, and functional impairments. Due to the lack of evidence on the long-term effects of COVID-19 healthcare providers may take into account research from other relevant and more extensively studied respiratory illnesses. The purpose of this case report is to highlight the use of available research from SARS-COV in the rehabilitation of a young, previously healthy patient with severe effects of COVID-19. CASE DESCRIPTION: The patient is a 45-year-old male diagnosed with COVID19 in May 2020. He was diagnosed with a severe case and admitted to the Intensive Care Unit with hypoxemia for 4 days. His past medical history included celiac disease, post-traumatic stress disorder, and two pulmonary embolisms from COVID-19 for which he was prescribed Apixaban. He was evaluated by physical therapy in the Veterans Affairs Telehealth system in September 2020. The patient's chief complaint was fatigue and inability to perform his usual functions. This was demonstrated by the inability to ambulate greater than 2 min without rest breaks. At the time of evaluation his gait speed was >35 m/s highlighting his severely deconditioned state. The patient was treated for 12 visits over 6 months using interval training with a rate of perceived exertion progression three days per week utilizing concepts from high intensity interval training. This intervention was based upon available research on treatments of similar respiratory conditions such as SARS-COV. OUTCOMES: The patient's meaningful functional improvements included the following: patient specific functional scale improved from a range of 0-2 to a range of 8-10, 2-minute step test from 93 to 100 steps, 5 times sit to stand from 15 to 11 seconds, and 6 -minute walk test from 540 m to 600 m. Patient's PROMIS score was also taken 4 months into treatment falling into normal ranges with a T-score of 47.7 for the global physical health score. DISCUSSION: Due to limited available evidence on the treatment of long-term effects of COVID19 clinicians may interpret the best evidence for similar conditions such as SAR-COV. In the absence of evidence for effective treatments in outpatient physical therapy for a patient with novel COVID-19, using evidence from conditions with similar physiological effects seemed to be an effective strategy. Interval training reduces the ventilatory demand of exercise and reduces the sense of breathing effort as sustained traditional aerobic exercise may not be tolerated in this population. This case highlights an approach that warrants further study in this population.

Chronic polyarthritis in an adolescent with cutaneous polyarteritis nodosa

Introduction: Polyarteritis nodosa (PAN) is a necrotizing vasculitis of medium/small arteries. It is a rare condition, especially in the pediatric age group. Cutaneous PAN (cPAN) is recognized as a separate entity. It is characterized by disease affecting the skin with no major organ system involvement. Objectives: Chronic polyarthritis is much less observed and can simulate juvenile idiopathic arthritis, which can delay diagnosis, as was the case with this patient. Methods: We report a 14-year-old boy, who presented to us with polyarthritis and myalgia as a first manifestation of cPAN. Results: This 14-year-old male adolescent presented with a history of arthritis in right shoulder, ankles, knees, elbows, fingers and toes, associated with myalgia, with partial improvement after the use of non-hormonal anti-inflammatory drugs. Two months later, he was diagnosed with juvenile idiopathic arthritis. Corticosteroids were prescribed in a dose of 20 mg/day, methotrexate 7.5 mg/week and folic acid. There was no clinical improvement. At this time, he start with fever and the appearance of a painful erythematous lesions in the lower limbs and arms, difficulty in walking, which were progressively getting worse, anorexia and weight loss during this period. He also had a history of oropharyngeal infection prior to beginning of these symptoms. At that time, he was treated with azithromycin for 5 days. As there was no improvement in his clinical condition, he sought the Emergency Room where he was admitted for investigation 3 months after the beginning of his symptoms. On physical examination, we found arthritis in the elbows, knees, ankles and joints of the hands, maculopapular rash in the ankles, muscle atrophy in the arms and legs, palpable and painful nodules on the right leg and right foot. Several laboratory tests were requested. Blood investigations showed anemia, leucocytosis, elevated CRP, ESR and ASLO titres, with normal liver and kidney functions, and normal urine 1. Syphilis, HIV, serology for Mycoplasma pneumoniae, leishmaniasis, Paracoccidioides brasiliensis, Epstein-Barr virus, cytomegalovirus, Zika and Chikungunya viruses, dengue, and parvovirus B19 were negative. HBsAg, hep c were negative. CRP and serology was negative for Coronavirus 19 (Covid-19). Chest Xray, echocardiogram, and ultrasound of the abdomen were normal. Lupus anticoagulant, and FR were negative. Other autoantibodies were negative. p-ANCA and c-ANCA were negative. Myelogram with normal immunophenotyping was found. A skin biopsy was suggestive of PAN showing perivascular lymphomononuclear inflammatory infiltrate, sometimes permeating the vascular wall. The presence of eosinophils and neutrophils with outbreaks of leukocytoclasia was noted, an absence of malignancy was also shown. With infectious, hematological and oncological causes aside, pulse therapy with methylprednisolone was started. After the first infusion, a significant improvement in myalgia and arthritis was observed, in addition to the disappearance of febrile peaks. Then, he started a monthly pulse therapy with cyclophosphamide and methylprednisolone. Four months after start this therapy, we observed improvement of skin lesions and in laboratory exams. Conclusion: Cutaneous PAN is a rare disease, especially in the pediatric age group. Its clinical manifestations are quite varied, making early diagnosis difficult. Joint involvement, when it occurs, is characterized by an acute and oligoarticular pattern in the knees and ankles. Chronic polyarthritis is much less observed and can simulate juvenile idiopathic arthritis, which can delay diagnosis, as was the case with this patient. We must consider the diagnosis of PAN in those patients with chronic polyarthritis, associated with cutaneous vasculitic manifestations and increased ASLO.

May macroglossia in COVID-19 be related not only to angioedema?

SARS-CoV-2 infection can lead to a variety of clinical manifestations. The occurrence of tongue swelling has recently reported in severe cases of COVID-19, and angioedema has suggested as the causative mechanism. Several factors, such as genetic predisposing factor and angiotensin-converting enzyme inhibitors (ACEI) therapies, have proposed to induce angioedema, especially as concerns patients requiring ICU treatments. Nevertheless, the question is still debated and other causes not yet recognized should be considered. Here we present a case of macroglossia occurred in a patient deceased for COVID-19 disease, who had no family history of angioedema and did not receive ACEI as antihypertensive drug. Histological and immune-histochemical analysis revealed tongue muscle atrophy with infiltrating macrophages suggesting repair mechanisms, as seen in nerve injury recovery. These new pathological findings may open new fields of study on the pathogenesis of SARS-CoV-2.

Magnesium supplementation alleviates corticosteroid-associated muscle atrophy in rats.

PURPOSE: Corticosteroid (CS) therapy for infectious and rheumatological diseases showed to decrease serum magnesium (Mg++) level and induce muscle atrophy in patients. The present study investigated the effects of Mg++ supplementation on preventing CS-induced muscle atrophy in an animal model, which provided experimental data for potential clinical translation. METHODS: Twelve 24-week-old male Sprague-Dawley rats were treated with lipopolysaccharide (LPS) and CS methylprednisolone (MPS) to induce muscle atrophy, with half of the rats also given daily 50 mg/kg Mg++ oral supplementation. Additional six rats without LPS + CS treatments were used as normal controls. After treatment for 6 weeks, serum was collected for Mg++ quantification, animal dual-energy X-ray absorptiometry (DXA) was performed for tissue composition, and the extensor digitorum longus (EDL) was collected for muscle functional test and histology including muscle fiber size, intramuscular fat infiltration and fiber typing. In vitro myotube atrophy model was used to study the in vitro effect associated with in vivo muscle atrophy. RESULTS: LPS + CS treatments induced hypomagnesemia while the serum Mg++ level was in normal range after Mg++ supplementation. DXA showed 53.0% lower fat percent and 29.7% higher lean mass in LPS + CS + Mg group when compared to LPS + CS group. Muscle functional test showed 22.2% higher specific twitch force and 40.3% higher specific tetanic force in LPS + CS + Mg group when compared to LPS + CS group. Histological analysis showed 4.1% higher proportion of muscle fibers area to total area and 63.6% lower intramuscular fat infiltration in EDL sections in LPS + CS + Mg group when compared to LPS + CS group. LPS + CS + Mg group had 33.0% higher area proportion and 29.4% higher cross-sectional area (CSA) of type IIb muscle fiber. Myoblast culture results showed that Mg++ supplementation group had larger myotube diameter. The mRNA expressions of the muscle atrophy marker genes MuRF1 and MAFbx were lower in Mg++ supplementation group both in vitro and in vivo. CONCLUSION: The current study demonstrated that Mg++ supplementation successfully alleviated CS-associated muscle atrophy in rats at both functional and morphology levels, indicating a translational potential for patients undergoing CS therapy. This study provided the evidence for the first time that Mg++ supplementation could prevent muscle atrophy-an adverse effect of CS therapy, currently also adopted for treating coronavirus disease 2019 (COVID-19).

Intensive Care Unit-Acquired Weakness: Not just Another Muscle Atrophying Condition.

Intensive care unit-acquired weakness (ICUAW) occurs in critically ill patients stemming from the critical illness itself, and results in sustained disability long after the ICU stay. Weakness can be attributed to muscle wasting, impaired contractility, neuropathy, and major pathways associated with muscle protein degradation such as the ubiquitin proteasome system and dysregulated autophagy. Furthermore, it is characterized by the preferential loss of myosin, a distinct feature of the condition. While many risk factors for ICUAW have been identified, effective interventions to offset these changes remain elusive. In addition, our understanding of the mechanisms underlying the long-term, sustained weakness observed in a subset of patients after discharge is minimal. Herein, we discuss the various proposed pathways involved in the pathophysiology of ICUAW, with a focus on the mechanisms underpinning skeletal muscle wasting and impaired contractility, and the animal models used to study them. Furthermore, we will explore the contributions of inflammation, steroid use, and paralysis to the development of ICUAW and how it pertains to those with the corona virus disease of 2019 (COVID-19). We then elaborate on interventions tested as a means to offset these decrements in muscle function that occur as a result of critical illness, and we propose new strategies to explore the molecular mechanisms of ICUAW, including serum-related biomarkers and 3D human skeletal muscle culture models.