Pectoralis muscle area measured at T4 level is closely associated with adverse COVID-19 outcomes in hospitalized patients.

OBJECTIVES: Skeletal muscle area (SMA) at T4 level on chest computed tomography (CT) is a newly available method that can be used as a surrogate sarcopenia marker. The objective of this study is to evaluate association of SMA with adverse COVID-19 outcomes in hospitalized patients. METHODS: Hospitalized COVID-19 patients were prospectively recorded in a database containing age, gender, date of admission, date of outcome (discharge, mortality, presence of intensive care unit (ICU) stay, additional coding information (comorbidities, superimposed conditions). Admission CT-scans were retrospectively evaluated for segmentation (bilateral pectoralis major/minor, erector spinae, levator scapulae, rhomboideus minor and major and transversospinalis muscles) and SMA calculation using 3-D slicer software. RESULTS: 167 cases were evaluated (68 male, 72 female, 140 survived, 27 dead). Muscle area was lower in patients with ICU stay (p=0.023, p=0.018, p=0.008) and mortality outcome (p=0.004, p=0.007, p=0.002) for pectoralis, back and SMA. In multivariate Cox-regression analysis, hazard ratio (HR) value for the pectoralis muscle area value below 2800 mm2 was found to be 3.138(95% CI: 1.171-8.413) for mortality and 2.361(95% CI: 1.012-5.505) for ICU. CONCLUSIONS: Pectoralis muscle area measured at T4 level with 3-D slicer was closely associated with adverse outcomes (mortality, ICU stay) in hospitalized COVID-19 patients. Since early treatment methods for COVID-19 are being evaluated, this method may be a useful adjunct to clinical decision making in regard to prioritization.

COVID-19 and sarcopenia-related traits: a bidirectional Mendelian randomization study.

Background: Emerging evidence suggested that coronavirus disease 2019 (COVID-19) patients were more prone to acute skeletal muscle loss and suffer sequelae, including weakness, arthromyalgia, depression and anxiety. Meanwhile, it was observed that sarcopenia (SP) was associated with susceptibility, hospitalization and severity of COVID-19. However, it is not known whether there is causal relationship between COVID-19 and SP-related traits. Mendelian randomization (MR) was a valid method for inferring causality. Methods: Data was extracted from the COVID-19 Host Genetic Initiative and the UK Biobank without sample overlapping. The MR analysis was performed with inverse variance weighted, weighted median, MR-Egger, RAPS and CAUSE, MR-APSS. Sensitivity analysis was conducted with MR-Egger intercept test, Cochran's Q test, MR-PRESSO to eliminate pleiotropy. Results: There was insufficient result in the MR-APSS method to support a direct causal relationship after the Bonferroni correction. Most other MR results were also nominally consistent with the MR-APSS result. Conclusions: Our study first explored the causal relationship between COVID-19 and SP-related traits, but the result indicated that they may indirectly interact with each other. We highlighted that older people had better absorb enough nutrition and strengthen exercise to directly cope with SP during the COVID-19 pandemic.

Anterior interosseous nerve syndrome following infection with COVID-19: a case report.

BACKGROUND: Various neurological manifestations associated with coronavirus disease 2019 have been increasingly reported. Herein, we report a rare case of anterior interosseous nerve syndrome, which occurred 5 days after the onset of coronavirus disease 2019. CASE PRESENTATION: A 62-year-old Asian woman with a history of coronavirus disease 2019 who developed a complete motor deficit in the left flexor pollicis longus and pronator quadratus without sensory deficits. The symptoms appeared as a sudden onset fatigue and severe pain of the left arm, 5 days after the onset of coronavirus disease 2019. She noticed paralysis of the left thumb at 2 weeks after the onset of coronavirus disease 2019. Electromyography assessment of the anterior interosseous nerve-dominated muscles revealed neurogenic changes such as positive sharp wave and fibrillation in flexor pollicis longus and pronator quadratus, confirming the diagnosis of anterior interosseous nerve syndrome. There were no other diseases that could have resulted in peripheral nerve palsy. We performed a functional reconstruction surgery of the thumb by tendon transfer from the extensor carpi radialis longus to the flexor pollicis longus. The patient reported a good patient-reported outcome (2.27 points in QuickDASH Disability/Symptom scoring and 5 points in Hand20 scoring) at final follow-up (1 year after the surgery). CONCLUSION: This case highlights the need for vigilance regarding the possible development of anterior interosseous nerve syndrome in patients with coronavirus disease 2019. Tendon transfer from extensor carpi radialis longus to flexor pollicis longus can provide good functional recovery for unrecovered motor paralysis after anterior interosseous nerve syndrome.

Feasibility and safety of Heavy Lifting Strength Training in Head and Neck Cancer survivors post-surgical neck dissection (the LIFTING trial).

BACKGROUND: Light-to-moderate intensity strength training (LMST) improves muscular strength, physical functioning, and some side effects in head and neck cancer survivors (HNCS). Heavy lifting strength training (HLST) may further improve these outcomes; however, it has not been studied in HNCS. The primary aim of the LIFTING trial was to examine the feasibility and safety of a HLST program in HNCS ≥1-year post-surgical neck dissection. METHODS: In this single-arm feasibility study, HNCS were asked to complete a twice weekly, 12-week, supervised HLST program, gradually progressing to lifting heavy loads of 80-90% of 1 repetition maximum (1RM) for barbell squat, bench press, and deadlift. The feasibility outcomes included recruitment rate, 1RM completion rate, program adherence, barriers, and motivation. The preliminary efficacy outcomes included changes in upper and lower body strength. RESULTS: Nine HNCS were recruited over an 8-month period during the COVID-19 pandemic. All 9 (100%) completed the 1RM tests and successfully progressed to heavy loads at approximately 5 weeks. The median attendance was 95.8% (range 71-100%), and few barriers were reported. Weight lifted increased for squat/leg press (median change: +34kg; 95% CI +25 to +47), bench press (median change: +6kg; 95% CI +2 to +10), and deadlift (median change: +12kg; 95% CI +7 to +24). No adverse events were reported and participants were motivated to continue HLST after the study. CONCLUSIONS: HLST appears feasible and safe for HNCS and may result in meaningful improvements in muscular strength. Future research should consider additional recruitment strategies and compare HLST to LMST in this understudied survivor population. TRIAL REGISTRATION: NCT04554667.

Idiopathic inflammatory myopathies: one year in review 2022.

Idiopathic inflammatory myopathies (IIM) are a heterogeneous group of disorders in which chronic inflammation of the skeletal muscle, leading to muscle weakness, is a common feature. Different phenotypes have been identified within the IIM spectrum based on extra-muscular manifestations, immunology, muscle histology, responsiveness to therapy, and prognosis. The pathogenesis, classification, treatment, and prognosis of the different IIM subtypes are subject to active discussion and research. This review highlights the most relevant literature published on this topic over the last year.

Altered tissue oxygenation in patients with post COVID-19 syndrome.

BACKGROUND: Post COVID-19 syndrome (PCS) is a complex condition with partly substantial impact on patients' social and professional life and overall life quality. Currently, the underlying cause(s) of PCS are unknown. Since PCS-specific symptoms could be associated with systemic alterations in tissue oxygen supply, we aimed to investigate changes in tissue oxygenation in patients with PCS. METHODS: A case-control study including 30 PCS patients (66.6 % males, 48.6 ± 11.2 years, mean time after (first) acute infection: 324 days), 16 cardiologic patients (CVD) (65.5 % males, 56.7 ± 6.3 years) and 11 young healthy controls (55 % males, 28.5 ± 7.4 years) was conducted. Near infrared spectroscopy (NIRS) was used to assess changes in tissue oxygenation during an arterial occlusion protocol on the non-dominant forearm (brachioradialis, 760/850 nm, 5 Hz). The protocol included 10-min rest, a 2-min baseline measurement followed by a 3-min ischemic period (upper-arm cuff, 50 mmHg above resting systolic blood pressure) and a 3-min reoxygenation period. PCS patients were grouped by presence of arterial hypertension and elevated BMI to assess the impact of risk factors. RESULTS: No differences in mean tissue oxygenation in the pre-occlusion phase existed between groups (p ≥ 0.566). During ischemia, comparisons of linear regressions slopes revealed slower oxygen desaturation for PCS patients (-0.064 %/s) compared to CVD patients (-0.08 %/s) and healthy subjects (-0.145 %/s) (p < 0.001). After cuff release, slowest speed for reoxygenation was detected in PCS patients at 0.84 %/s compared to CVD patients (1.04 %/s) and healthy controls (CG: 2.07 %/s) (p < 0.001). The differences between PCS patients and CVD patients during ischemia remained significant also after correction for risk factors. Analyses of complications during acute infection, persistence of PCS symptoms (time after acute infection), or PCS severity (number of lead symptoms) as confounding factors did not reveal a significant effect. CONCLUSIONS: This study provides evidence that the rate of tissue oxygen consumption is persistently altered in PCS and that PCS patients show an even slower decline in tissue oxygenation during occlusion than CVD patients. Our observations may at least partly explain PCS-specific symptoms such as physical impairment and fatigue.

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.

Prevalence and clinical implications of abnormal body composition phenotypes in patients with COVID-19: a systematic review.

BACKGROUND: The impact of body composition (BC) abnormalities on COVID-19 outcomes remains to be determined. OBJECTIVES: We summarized the evidence on BC abnormalities and their relationship with adverse clinical outcomes in patients with COVID-19. METHODS: A systematic search was conducted up until 26 September, 2022 for observational studies using BC techniques to quantify skeletal muscle mass (or related compartments), muscle radiodensity or echo intensity, adipose tissue (AT; or related compartments), and phase angle (PhA) in adults with COVID-19. Methodological quality of studies was assessed using the Newcastle-Ottawa Scale. A synthesis without meta-analysis was conducted to summarize the prevalence of BC abnormalities and their significant associations with clinical outcomes. RESULTS: We included 62 studies (69.4% low risk of bias) with 12-1138 participants, except 3 studies with ≤490,301 participants. Using CT and different cutoff values, prevalence ranged approximately from 22% to 90% for low muscle mass, 12% to 85% for low muscle radiodensity, and 16% to 70% for high visceral AT. Using BIA, prevalence of high FM was 51%, and low PhA was 22% to 88%. Mortality was inversely related to PhA (3/4 studies) and positively related to intra- and intermuscular AT (4/5 studies), muscle echo intensity (2/2 studies), and BIA-estimated FM (2/2 studies). Intensive care unit (ICU) admission was positively related to visceral AT (6/7 studies) and total AT (2/3 studies). Disease severity and hospitalization outcomes were positively related to intra- and intermuscular AT (2/2 studies). Inconsistent associations were found for the rest of the BC measures and hospitalization outcomes. CONCLUSIONS: Abnormalities in BC were prevalent in patients with COVID-19. Although conflicting associations were observed among certain BC abnormalities and clinical outcomes, higher muscle echo intensity (reflective of myosteatosis) and lower PhA were more consistently associated with greater mortality risk. Likewise, high intra- and intermuscular AT and visceral AT were associated with mortality and ICU admission, respectively. This trial was registered at PROSPERO as CRD42021283031.

Sarcopenia - Definition, Radiological Diagnosis, Clinical Significance. / Sarkopenie ­ Definition, radiologische Erfassung, klinische Bedeutung.

BACKGROUND: Sarcopenia is an age-related syndrome characterized by a loss of muscle mass and strength. As a result, the independence of the elderly is reduced and the hospitalization rate and mortality increase. The onset of sarcopenia often begins in middle age due to an unbalanced diet or malnutrition in association with a lack of physical activity. This effect is intensified by concomitant diseases such as obesity or metabolic diseases including diabetes mellitus. METHOD: With effective preventative diagnostic procedures and specific therapeutic treatment of sarcopenia, the negative effects on the individual can be reduced and the negative impact on health as well as socioeconomic effects can be prevented. Various diagnostic options are available for this purpose. In addition to basic clinical methods such as measuring muscle strength, sarcopenia can also be detected using imaging techniques like dual X-ray absorptiometry (DXA), computed tomography (CT), magnetic resonance imaging (MRI), and sonography. DXA, as a simple and cost-effective method, offers a low-dose option for assessing body composition. With cross-sectional imaging techniques such as CT and MRI, further diagnostic possibilities are available, including MR spectroscopy (MRS) for noninvasive molecular analysis of muscle tissue. CT can also be used in the context of examinations performed for other indications to acquire additional parameters of the skeletal muscles (opportunistic secondary use of CT data), such as abdominal muscle mass (total abdominal muscle area - TAMA) or the psoas as well as the pectoralis muscle index. The importance of sarcopenia is already well studied for patients with various tumor entities and also infections such as SARS-COV2. RESULTS AND CONCLUSION: Sarcopenia will become increasingly important, not least due to demographic changes in the population. In this review, the possibilities for the diagnosis of sarcopenia, the clinical significance, and therapeutic options are described. In particular, CT examinations, which are repeatedly performed on tumor patients, can be used for diagnostics. This opportunistic use can be supported by the use of artificial intelligence. KEY POINTS: · Sarcopenia is an age-related syndrome with loss of muscle mass and strength.. · Early detection and therapy can prevent negative effects of sarcopenia.. · In addition to DEXA, cross-sectional imaging techniques (CT, MRI) are available for diagnostic purposes.. · The use of artificial intelligence (AI) offers further possibilities in sarcopenia diagnostics.. CITATION FORMAT: · Vogele D, Otto S, Sollmann N et al. Sarcopenia - Definition, Radiological Diagnosis, Clinical Significance. Fortschr Röntgenstr 2023; 195: 393 - 405.

Weekly screening of youth male football players: a 14-week longitudinal investigation of interactions between groin pain and long lever adductor squeeze strength.

OBJECTIVES: To explore relationships between groin pain and adductor squeeze strength in male academy football players over a 14-week period. DESIGN: Longitudinal cohort study. METHODS: Weekly monitoring of youth male football players consisted of reporting groin pain and testing long lever adductor squeeze strength. Players who reported groin pain at any time during the study period were stratified into the "groin pain" group while players who did not report pain remained in the "no groin pain" group. Baseline squeeze strength was retrospectively compared between groups. Players that developed groin pain were examined via repeated measures ANOVA at four timepoints: baseline, last squeeze before pain, pain onset, and return to pain-free. RESULTS: 53 players were included (age 14.4 ±â€¯1.6 years). Baseline squeeze strength was not different between players in the "groin pain" (n = 29, 4.35 ±â€¯0.89 N/kg) versus "no groin pain" group (n = 24, 4.33 ±â€¯0.90 N/kg, p = 0.83). At a group level, players with no groin pain maintained similar adductor squeeze strength throughout 14 weeks (p > 0.05). Compared to baseline (4.33 ±â€¯0.90 N/kg), players with groin pain had decreased adductor squeeze strength at the last squeeze before pain (3.91 ±â€¯0.85 N/kg, p = 0.003) and at pain onset (3.58 ±â€¯0.78 N/kg, p < 0.001). Adductor squeeze strength at the point where pain subsided (4.06 ±â€¯0.95 N/kg) was not different from baseline (p = 0.14). CONCLUSIONS: Decreases in adductor squeeze strength manifest one-week prior to groin pain onset and further decrease at pain onset. Weekly adductor squeeze strength may be an early detector for groin pain in youth male football players.

Patients with Post-Covid-19 Syndrome are at risk of malnutrition and obesity: findings of outpatient follow-up / Pacientes com Síndrome Pós-Covid-19 apresentam risco de desnutrição e obesidade: achados de um ambulatório de seguimento

ABSTRACT Objective To evaluate the nutritional and functional status, swallowing disorders, and musculoskeletal manifestations of patients with Post-Covid-19 Syndrome, stratified by the Appendicular Skeletal Muscle Mass Index. Methods This is a cross-sectional study with patients diagnosed with Post-Covid-19 Syndrome after discharge from the intensive care unit of a university hospital. The evaluated outcomes were: nutritional status (Mini Nutritional Assessment, bioimpedance and anthropometry), swallowing disorders (Dysphagia Risk Evaluation Protocol), functional status (Post-Covid-19 Functional Status Scale), and musculoskeletal manifestations. According to the Appendicular Skeletal Muscle Mass Index, patients were stratified in terms of loss or not loss of muscle mass. Results Thirty-eight patients were included in the study, 20 stratified into the no loss of muscle mass group (17 females; 49.45±12.67 years) and 18 into the loss of muscle mass group (18 males; 61.89±12.49 years). Both groups were at risk of malnutrition (Mini Nutritional Assessment scores between 17-23.5 points; No Loss of Muscle Mass Group: 21.82±3.93; Loss of Muscle Mass Group: 23.33±3.41) and obesity (No Loss of Muscle Mass Group: 33.76±6.34; Loss of Muscle Mass Group: 30.23±3.66). The groups differed in terms of bioimpedance parameters (except fat mass) and age. However, there were no differences in swallowing alterations, functional status, and musculoskeletal manifestations. Conclusion Patients with Post-Covid-19 Syndrome, stratified according to the Appendicular Skeletal Muscle Mass Index, were at risk of malnutrition and obesity. The persistence of fatigue, weakness, myalgia and arthralgia at 6 months after hospital discharge is noteworthy. These findings emphasize the importance of comprehensive care for patients with Post-Covid-19 Syndrome.

RESUMO Objetivo Avaliar o estado nutricional, status funcional, alterações de deglutição e manifestações musculoesqueléticas de pacientes com Síndrome Pós-Covid-19, estratificados pelo Índice de Massa Muscular Esquelética Apendicular. Métodos Estudo transversal composto por pacientes diagnosticados com a Síndrome Pós-Covid-19 que estiveram internados na Unidade de Terapia Intensiva de um hospital universitário. Os desfechos avaliados foram: estado nutricional (Mini Avaliação Nutricional; bioimpedância e antropometria), alterações de deglutição (Protocolo Fonoaudiológico de Avaliação do Risco de Disfagia), status funcional (Post-Covid-19 Functional Status Scale) e manifestações musculoesqueléticas. Os pacientes foram classificados, quanto à perda de massa muscular conforme o Índice de Massa Muscular Esquelética Apendicular, em grupo sem e com perda de massa muscular. Resultados Foram inseridos no estudo 38 pacientes, 20 no grupo sem perda de massa muscular (17 deles do sexo feminino; 49,45±12,67 anos) e 18 no grupo com perda de massa muscular (todos do sexo masculino; 61,89±12,49 anos). Os pacientes de ambos os grupos apresentaram risco de desnutrição (escores Mini Avaliação Nutricional entre 17-23.5 pontos; Grupo Sem Perda de Massa Muscular: 21,82±3,93; Grupo Com Perda de Massa Muscular: 23,33±3,41) e obesidade (Grupo Sem Perda de Massa Muscular: 33,76±6,34; Grupo Com Perda de Massa Muscular: 30,23±3,66). Os grupos diferiram quanto aos parâmetros da bioimpedância (exceto massa gorda) e idade. Entretanto, não foram observadas diferenças na deglutição, status funcional e manifestações musculoesqueléticas. Conclusão Os pacientes com Síndrome Pós-Covid-19, estratificados conforme o Índice de Massa Muscular Esquelética Apendicular, apresentaram risco de desnutrição e obesidade. Destaca-se a persistência de fadiga, fraqueza, mialgia e artralgia após seis meses da alta hospitalar. Esses achados ressaltam a importância do cuidado integral ao paciente com a Síndrome Pós-Covid-19.

Electrical stimulation to regain lower extremity muscle perfusion and endurance in patients with post-acute sequelae of SARS CoV-2: A randomized controlled trial.

Muscle deconditioning and impaired vascular function in the lower extremities (LE) are among the long-term symptoms experienced by COVID-19 patients with a history of severe illness. These symptoms are part of the post-acute sequelae of Sars-CoV-2 (PASC) and currently lack evidence-based treatment. To investigate the efficacy of lower extremity electrical stimulation (E-Stim) in addressing PASC-related muscle deconditioning, we conducted a double-blinded randomized controlled trial. Eighteen (n = 18) patients with LE muscle deconditioning were randomly assigned to either the intervention (IG) or the control (CG) group, resulting in 36 LE being assessed. Both groups received daily 1 h E-Stim on both gastrocnemius muscles for 4 weeks, with the device functional in the IG and nonfunctional in the CG. Changes in plantar oxyhemoglobin (OxyHb) and gastrocnemius muscle endurance (GNMe) in response to 4 weeks of daily 1 h E-Stim were assessed. At each study visit, outcomes were measured at onset (t0 ), 60 min (t60 ), and 10 min after E-Stim therapy (t70 ) by recording ΔOxyHb with near-infrared spectroscopy. ΔGNMe was measured with surface electromyography at two time intervals: 0-5 min (Intv1 ) and: 55-60 min (Intv2 ). Baseline OxyHb decreased in both groups at t60 (IG: p = 0.046; CG: p = 0.026) and t70 (IG = p = 0.021; CG: p = 0.060) from t0 . At 4 weeks, the IG's OxyHb increased from t60 to t70 (p < 0.001), while the CG's decreased (p = 0.003). The IG had higher ΔOxyHb values than the CG at t70 (p = 0.004). Baseline GNMe did not increase in either group from Intv1 to Intv2 . At 4 weeks, the IG's GNMe increased (p = 0.031), whereas the CG did not change. There was a significant association between ΔOxyHb and ΔGNMe (r = 0.628, p = 0.003) at 4 weeks in the IG. In conclusion, E-Stim can improve muscle perfusion and muscle endurance in individuals with PASC experiencing LE muscle deconditioning.

Quantitative muscle magnetic resonance imaging depicts microstructural abnormalities but no signs of inflammation or dystrophy in post-COVID-19 condition.

BACKGROUND AND PURPOSE: Post-COVID-19 condition (PCC) has high impact on quality of life, with myalgia and fatigue affecting at least 25% of PCC patients. This case-control study aims to noninvasively assess muscular alterations via quantitative muscle magnetic resonance imaging (MRI) as possible mechanisms for ongoing musculoskeletal complaints and premature exhaustion in PCC. METHODS: Quantitative muscle MRI was performed on a 3 Tesla MRI scanner of the whole legs in PCC patients compared to age- and sex-matched healthy controls, including a Dixon sequence to determine muscle fat fraction (FF), a multi-echo spin-echo sequence for quantitative water mapping reflecting putative edema, and a diffusion-weighted spin-echo echo-planar imaging sequence to assess microstructural alterations. Clinical examination, nerve conduction studies, and serum creatine kinase were performed in all patients. Quantitative muscle MRI results were correlated to the results of the 6-min walk test and standardized questionnaires assessing quality of life, fatigue, and depression. RESULTS: Twenty PCC patients (female: n = 15, age = 48.8 ± 10.1 years, symptoms duration = 13.4 ± 4.2 months, body mass index [BMI] = 28.8 ± 4.7 kg/m2 ) were compared to 20 healthy controls (female: n = 15, age = 48.1 ± 11.1 years, BMI = 22.9 ± 2.2 kg/m2 ). Neither FF nor T2 revealed signs of muscle degeneration or inflammation in either study groups. Diffusion tensor imaging (DTI) revealed reduced mean, axial, and radial diffusivity in the PCC group. CONCLUSIONS: Quantitative muscle MRI did not depict any signs of ongoing inflammation or dystrophic process in the skeletal muscles in PCC patients. However, differences observed in muscle DTI depict microstructural abnormalities, which may reflect potentially reversible fiber hypotrophy due to deconditioning. Further longitudinal and interventional studies should prove this hypothesis.

Chronic inflammatory demyelinating polyradiculoneuropathy-associated tremor: Phenotype and pathogenesis.

BACKGROUND AND PURPOSE: Tremor in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is underrecognized, and the pathophysiology remains incompletely understood. This study evaluated tremor in CIDP and tested the hypothesis, established in other demyelinating neuropathies, that tremor occurs due to mistimed peripheral inputs affecting central motor processing. Additionally, the tremor stability index (TSI) was calculated with the hypothesis that CIDP-related tremor is more variable than other tremor disorders. METHODS: Consecutive patients with typical CIDP were prospectively recruited from neuromuscular clinics. Alternative causes of neuropathy and tremor were excluded. Cross-sectional clinical assessment and extensive tremor study recordings were undertaken. Pearson correlation coefficient was used to compare nerve conduction studies and tremor characteristics, and t-test was used for comparisons between groups. RESULTS: Twenty-four patients with CIDP were included. Upper limb postural and action tremor was present in 66% and was mild according to the Essential Tremor Rating Assessment Scale. Tremor did not significantly impact disability. Surface electromyography (EMG) found high-frequency spectral peaks in deltoid (13.73 ± 0.66 Hz), biceps brachii (11.82 ± 0.91 Hz), and extensor carpi radialis (11.87 ± 0.91 Hz) muscles, with lower peaks in abductor pollicis brevis EMG (6.07 ± 0.45 Hz) and index finger accelerometry (6.53 ± 0.42 Hz). Tremor was unchanged by weight loading but correlated with ulnar nerve F-wave latency and median nerve sensory amplitude. TSI (2.3 ± 0.1) was significantly higher than essential tremor. CONCLUSIONS: Postural tremor is a common feature in CIDP. Tremor was unaffected by weight loading, typical of centrally generated tremors, although there was a correlation with peripheral nerve abnormalities. The high beat-to-beat variability on TSI and gradation of peak frequencies further suggest a complex pathophysiology. These findings may assist clinicians with the diagnosis of neuropathic tremor.

Recent advances in cell-based and cell-free therapeutic approaches for sarcopenia.

Sarcopenia is a progressive loss of muscle mass and function that is connected with increased hospital expenditures, falls, fractures, and mortality. Although muscle loss has been related to aging, injury, hormonal imbalances, and diseases such as malignancies, chronic obstructive pulmonary disease, heart failure, and kidney failure, the underlying pathogenic mechanisms of sarcopenia are unclear. Exercise-based interventions and multimodal strategies are currently being considered as potential therapeutic approaches to prevent or treat these diseases. Although drug therapy research is ongoing, no drug has yet been proven to have a substantial safety and clinical value to be the first drug therapy to be licensed for sarcopenia. To better understand the molecular alterations underlying sarcopenia and effective treatments, we review leading research and available findings from the systemic change to the muscle-specific microenvironment. Furthermore, we explore possible mechanisms of sarcopenia and provide new knowledge for the development of novel cell-free and cell-based therapeutics. This review will assist researchers in developing better therapies to improve muscle health in the elderly.

The Impact of Long COVID-19 on Muscle Health.

COVID-19 negatively impacts several organs and systems weeks or months after initial diagnosis. Skeletal muscle can be affected, leading to fatigue, lower mobility, weakness, and poor physical performance. Older adults are at increased risk of developing musculoskeletal symptoms during long COVID. Systemic inflammation, physical inactivity, and poor nutritional status are some of the mechanisms leading to muscle dysfunction in individuals with long COVID. Current evidence suggests that long COVID negatively impacts body composition, muscle function, and quality of life. Muscle mass and function assessments can contribute toward the identification, diagnosis, and management of poor muscle health resulting from long COVID.

The Cytokine Growth Differentiation Factor-15 and Skeletal Muscle Health: Portrait of an Emerging Widely Applicable Disease Biomarker.

Growth differentiation factor 15 (GDF-15) is a stress-induced transforming growth factor-ß superfamily cytokine with versatile functions in human health. Elevated GDF-15 blood levels associate with multiple pathological conditions, and are currently extensively explored for diagnosis, and as a means to monitor disease progression and evaluate therapeutic responses. This review analyzes GDF-15 in human conditions specifically focusing on its association with muscle manifestations of sarcopenia, mitochondrial myopathy, and autoimmune and viral myositis. The use of GDF-15 as a widely applicable health biomarker to monitor muscle disease is discussed, and its potential as a therapeutic target is explored.

COVID-19 Mimics Pulmonary Dysfunction in Muscular Dystrophy as a Post-Acute Syndrome in Patients.

Although progressive wasting and weakness of respiratory muscles are the prominent hallmarks of Duchenne muscular dystrophy (DMD) and long-COVID (also referred as the post-acute sequelae of COVID-19 syndrome); however, the underlying mechanism(s) leading to respiratory failure in both conditions remain unclear. We put together the latest relevant literature to further understand the plausible mechanism(s) behind diaphragm malfunctioning in COVID-19 and DMD conditions. Previously, we have shown the role of matrix metalloproteinase-9 (MMP9) in skeletal muscle fibrosis via a substantial increase in the levels of tumor necrosis factor-α (TNF-α) employing a DMD mouse model that was crossed-bred with MMP9-knockout (MMP9-KO or MMP9-/-) strain. Interestingly, recent observations from clinical studies show a robust increase in neopterin (NPT) levels during COVID-19 which is often observed in patients having DMD. What seems to be common in both (DMD and COVID-19) is the involvement of neopterin (NPT). We know that NPT is generated by activated white blood cells (WBCs) especially the M1 macrophages in response to inducible nitric oxide synthase (iNOS), tetrahydrobiopterin (BH4), and tetrahydrofolate (FH4) pathways, i.e., folate one-carbon metabolism (FOCM) in conjunction with epigenetics underpinning as an immune surveillance protection. Studies from our laboratory, and others researching DMD and the genetically engineered humanized (hACE2) mice that were administered with the spike protein (SP) of SARS-CoV-2 revealed an increase in the levels of NPT, TNF-α, HDAC, IL-1ß, CD147, and MMP9 in the lung tissue of the animals that were subsequently accompanied by fibrosis of the diaphragm depicting a decreased oscillation phenotype. Therefore, it is of interest to understand how regulatory processes such as epigenetics involvement affect DNMT, HDAC, MTHFS, and iNOS that help generate NPT in the long-COVID patients.

Novel nutritional strategies to prevent muscle wasting.

PURPOSE OF REVIEW: Muscle wasting in critical illness has proven to be refractory to physical rehabilitation, and to conventional nutritional strategies. This presents one of the central challenges to critical care medicine in the 21st century. Novel strategies are needed that facilitate nutritional interventions, identify patients that will benefit and have measurable, relevant benefits. RECENT FINDINGS: Drug repurposing was demonstrated to be a powerful technique in the coronavirus disease 2019 pandemic, and may have similar applications to address the metabolic derangements of critical illness. Newer biological signatures may aid the application of these techniques and the association between changes in urea:creatinine ratio and the development of skeletal muscle wasting is increasing. A core outcome set for nutrition interventions in critical illness, supported by multiple international societies, was published earlier this year should be adopted by future nutrition trials aiming to attenuate muscle wasting. SUMMARY: The evidence base for the lack of efficacy for conventional nutritional strategies in preventing muscle wasting in critically ill patients continues to grow. Novel strategies such as metabolic modulators, patient level biological signatures of nutritional response and standardized outcome for measurements of efficacy will be central to future research and clinical care of the critically ill patient.