Usefulness of Platelet-to-Lymphocyte Ratio as a Marker of Sarcopenia for Critical Limb Threatening Ischemia.

BACKGROUND: Sarcopenia is a factor of poor prognosis for patients with critical limb threatening ischemia (CLTI), but its diagnosis requires imaging measurements and is time consuming. We investigated whether preoperative platelet-to-lymphocyte ratio (PLR) could be an easy and rapid marker of sarcopenia. METHODS: Patients treated for CLTI between January 2019 and July 2019 were included in this single-center retrospective study. Sarcopenia was defined by a psoas muscle index (PMI) <5.5 cm2/m2 in men, and <4.0 cm2/m2 in women. PLR was calculated for all patients based on their systematic preoperative blood analysis. The diagnostic power of PLR was analyzed through a receiver operating characteristic (ROC) curve. Early outcomes of sarcopenic patients in terms of 30-day mortality and 30-day morbidity were retrieved. RESULTS: Sixty-four patients were included in the study: 48 nonsarcopenic patients (mean PMI 7.34 cm2/m2; interquartile range [IQR] 6.58-8.01) and 16 sarcopenic patients (mean PMI 4.30 cm2/m2; IQR 3.45-5.17). No difference was found between both groups regarding patient demographics, clinical characteristics, cardiovascular risk factors, comorbidities, or revascularization modalities. PLR was significantly higher in the sarcopenic group (mean 332.1; IQR 158.2-320.7) compared with the nonsarcopenic group (mean 204.6; IQR 133.8-265.6) (P = 0.02). A PLR value ≥292.5 was shown to be a diagnostic marker for sarcopenia based on the ROC curve (sensitivity 31.3%, specificity 91.7%). Thirty-day mortality was 12.5% in the sarcopenic group and 2.1% in the nonsarcopenic group (P = 0.15); 30-day morbidity was 56.3% in the sarcopenic group and 10.4% in the nonsarcopenic group (P < 0.001). CONCLUSIONS: PLR might help identifying a subgroup of CTLI patients associated with poor prognosis but does not seem appropriate to be used as a marker of sarcopenia given its low sensitivity.

Long Term Follow-Up of Sarcopenia and Malnutrition after Hospitalization for COVID-19 in Conventional or Intensive Care Units.

BACKGROUND: The post-COVID-19 condition, defined as COVID-19-related signs and symptoms lasting at least 2 months and persisting more than 3 months after infection, appears now as a public health issue in terms of frequency and quality of life alterations. Nevertheless, few data are available concerning long term evolution of malnutrition and sarcopenia, which deserve further attention. METHOD: Sarcopenia was investigated prospectively, together with weight evolution, at admission and at 3 and 6 months after hospital discharge in 139 COVID-19 patients, using the European Working Group on Sarcopenia in Older People (EWGSOP2) criteria, associating both decreased muscle strength and muscle mass, assessed, respectively, with hand dynamometer and dual-energy X-ray absorptiometry. RESULTS: Of the 139 patients, 22 presented with sarcopenia at 3 months; intensive care units (ICU) length of stay was the sole factor associated with sarcopenia after multivariate analysis. Although the entire group did not demonstrate significant weight change, weight decreased significantly in the sarcopenia group (Five and eight patients, showing, respectively, >5 or >10% weight decrease). Interestingly, at 6 months, 16 of the 22 patients recovered from sarcopenia and their weight returned toward baseline values. CONCLUSIONS: Sarcopenia and malnutrition are frequently observed in patients hospitalized for COVID-19, even 3 months after infection occurrence, but can largely be reversed at 6 months after discharge. Enhanced patient care is needed in sarcopenic patients, particularly during long stays in an ICU.

A recurrent RYR1 mutation associated with early-onset hypotonia and benign disease course.

The ryanodine receptor RyR1 is the main sarcoplasmic reticulum Ca2+ channel in skeletal muscle and acts as a connecting link between electrical stimulation and Ca2+-dependent muscle contraction. Abnormal RyR1 activity compromises normal muscle function and results in various human disorders including malignant hyperthermia, central core disease, and centronuclear myopathy. However, RYR1 is one of the largest genes of the human genome and accumulates numerous missense variants of uncertain significance (VUS), precluding an efficient molecular diagnosis for many patients and families. Here we describe a recurrent RYR1 mutation previously classified as VUS, and we provide clinical, histological, and genetic data supporting its pathogenicity. The heterozygous c.12083C>T (p.Ser4028Leu) mutation was found in thirteen patients from nine unrelated congenital myopathy families with consistent clinical presentation, and either segregated with the disease in the dominant families or occurred de novo. The affected individuals essentially manifested neonatal or infancy-onset hypotonia, delayed motor milestones, and a benign disease course differing from classical RYR1-related muscle disorders. Muscle biopsies showed unspecific histological and ultrastructural findings, while RYR1-typical cores and internal nuclei were seen only in single patients. In conclusion, our data evidence the causality of the RYR1 c.12083C>T (p.Ser4028Leu) mutation in the development of an atypical congenital myopathy with gradually improving motor function over the first decades of life, and may direct molecular diagnosis for patients with comparable clinical presentation and unspecific histopathological features on the muscle biopsy.

Sarcopenia and peripheral arterial disease: a systematic review.

BACKGROUND: Patients with lower extremity peripheral arterial disease (PAD) and sarcopenia are a population at risk requiring specific and targeted care. The aim of this review is to gather all relevant studies associating sarcopenia and PAD and to identify the underlying pathophysiological mechanisms as well as potential therapeutic strategies to improve skeletal muscle function. METHODS: A systematic review was carried out following the recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). RESULTS: Data extraction allowed the evaluation of 140 publications; 87 met the inclusion criteria; of which 79 were included in the final review, reporting sufficient data for epidemiological and diagnostic criteria, mechanical analysis, and therapeutic approaches. Epidemiological analysis and diagnostic criteria were based on 18 studies following 2362 PAD patients [31.39% (SD 7.61) women], aged 72.42 (SD 2.84); sarcopenia was present in 34.63% (SD 12.86) of the patients. Mechanical and pathway analysis were based on five animal studies and 29 clinical reports, showing significantly altered muscle strength and function in 1352 PAD patients [26.49% (SD 17.32) women], aged 67.67 (SD 5.14) years; impaired muscle histology in 192 PAD patients (9.2% (SD 11.22) women), aged 64.3 (SD 0.99) years; +58.63% (SD 25.48) of oxidative stress in 69 PAD patients [16.96% (SD 8.10) women], aged 63.17 (SD 1.43) years; mitochondriopathy in 153 PAD patients [29.39% (SD 28.27) women], aged 63.50 (SD 1.83) years; +15.58% (SD 7.41) of inflammation in 900 PAD patients [40.77% (SD 3.71) women], aged 74.88 (SD 2.76) years; and altered signalling pathways in 51 PAD patients [34.45% (SD 32.23) women], aged 72.25 (SD 5.25) years. Therapeutic approaches analysis was based on seven animal studies and 21 clinical reports. In total, 884 patients followed an exercise therapy, and 18 received an angiogenesis treatment; 30.84% (SD 17.74) were women. Mean ages of patients studied were 66.85 (SD 3.96). CONCLUSIONS: Sarcopenia and lower extremity PAD have musculoskeletal consequences that directly impair patients' quality of life and prognosis. Although PAD is primarily a vascular disease, all etiological factors of sarcopenia identified so far are present in PAD. Indeed, both sarcopenia and PAD are accompanied by oxidative stress, skeletal muscle mitochondrial impairments, inflammation, inhibition of specific pathways regulating muscle synthesis or protection (i.e. IGF-1, RISK, and SAFE), and activation of molecules associated with muscle degradation. To date, besides revascularization, the best therapeutic strategy includes exercise, but approaches targeting the underlying mechanisms still deserve further studies.

Skeletal and Respiratory Muscle Dysfunctions in Pulmonary Arterial Hypertension.

Pulmonary arterial hypertension (PAH) is a rare disease, which leads to the progressive loss and remodeling of the pulmonary vessels, right heart failure, and death. Different clinical presentations can be responsible for such a bad prognosis disease and the underlying mechanisms still need to be further examined. Importantly, skeletal and respiratory muscle abnormalities largely contribute to the decreased quality of life and exercise intolerance observed in patients with PAH. At the systemic level, impaired oxygen supply through reduced cardiac output and respiratory muscle dysfunctions, which potentially result in hypoxemia, is associated with altered muscles vascularization, inflammation, enhanced catabolic pathways, and impaired oxygen use through mitochondrial dysfunctions that are likely participate in PAH-related myopathy. Sharing new insights into the pathological mechanisms of PAH might help stimulate specific research areas, improving the treatment and quality of life of PAH patients. Indeed, many of these muscular impairments are reversible, strongly supporting the development of effective preventive and/or therapeutic approaches, including mitochondrial protection and exercise training.

The Rise of Mitochondria in Peripheral Arterial Disease Physiopathology: Experimental and Clinical Data.

Peripheral arterial disease (PAD) is a frequent and serious condition, potentially life-threatening and leading to lower-limb amputation. Its pathophysiology is generally related to ischemia-reperfusion cycles, secondary to reduction or interruption of the arterial blood flow followed by reperfusion episodes that are necessary but also-per se-deleterious. Skeletal muscles alterations significantly participate in PAD injuries, and interestingly, muscle mitochondrial dysfunctions have been demonstrated to be key events and to have a prognosis value. Decreased oxidative capacity due to mitochondrial respiratory chain impairment is associated with increased release of reactive oxygen species and reduction of calcium retention capacity leading thus to enhanced apoptosis. Therefore, targeting mitochondria might be a promising therapeutic approach in PAD.

Beneficial Effect of Exercise on Cognitive Function during Peripheral Arterial Disease: Potential Involvement of Myokines and Microglial Anti-Inflammatory Phenotype Enhancement.

Peripheral arterial disease (PAD), leading to intermittent claudication, critical ischemia with rest pain, and/or tissue damage, is a public health issue associated with significant morbidity and mortality. Little is known about the link between PAD, cognitive function, and whether exercise might reduce cognitive dysfunction in PAD patients, as previously observed concerning both quality of life and prognosis. This review highlights the fact that patients suffering from PAD often demonstrate cognitive dysfunction characterized by reduced performance in nonverbal reasoning, reduced verbal fluency, and decreased information processing speed and a greater risk for progression toward dementia. Further, the data presented support that physical exercise, likely through myokine secretion and microglial anti-inflammatory phenotype enhancement, might participate in the cognition protection in common clinical settings.