Correlation Between Early Serum Myoglobin Levels and the Incidence and Prognosis of Intensive Care Unit-Acquired Weakness (ICU-AW) in Septic Shock Patients: A Comparative Study.

Intensive Care Unit-acquired weakness (ICU-AW) is a common complication that significantly impedes patient recovery. In the study, we investigated the correlation between early serum myoglobin levels in patients with septic shock due to pneumonia, and the incidence of ICU-AW, duration of mechanical ventilation, and prognosis. Patients were classified based on the development of ICU-AW within the first 10 days of ICU admission. We measured serum myoglobin levels upon ICU entry, and analyzed demographic data, APACHE II scores, use of mechanical ventilation, and clinical outcomes, including mortality and duration of mechanical ventilation. The results indicated significantly elevated serum myoglobin levels in the ICU-AW group, correlated with prolonged mechanical ventilation and increased mortality. ROC analysis revealed myoglobin as a promising biomarker for predicting ICU-AW, with an area under the curve of 0.843 (95% CI: 0.819~0.867), demonstrating a sensitivity of 76.00% and specificity of 82.30%. These findings underscored serum myoglobin as a predictive biomarker for early ICU-AW in septic shock patients, highlighting its potential to guide clinical decision-making.

Caffeine-induced hypokalemia: a case report.

BACKGROUND: With an increase in the global popularity of coffee, caffeine is one of the most consumed ingredients of modern times. However, the consumption of massive amounts of caffeine can lead to severe hypokalemia. CASE PRESENTATION: A 29-year-old man without a specific past medical history was admitted to our hospital with recurrent episodes of sudden and severe lower-extremity weakness. Laboratory tests revealed low serum potassium concentration (2.6-2.9 mmol/L) and low urine osmolality (100-130 mOsm/kgH2O) in three such prior episodes. Urinary potassium/urinary creatinine ratio was 12 and 16 mmol/gCr, respectively. The patient was not under medication with laxatives, diuretics, or herbal remedies. Through an in-depth interview, we found that the patient consumed large amounts of caffeine-containing beverages daily, which included > 15 cups of coffee, soda, and various kinds of tea. After the cessation of coffee intake and concomitant intravenous potassium replacement, the symptoms rapidly resolved, and the serum potassium level normalized. CONCLUSIONS: An increased intracellular shift of potassium and increased loss of potassium in urine due to the diuretic action have been suggested to be the causes of caffeine-induced hypokalemia. In cases of recurring hypokalemia of unknown cause, high caffeine intake should be considered.

Identifying molecular targets for reverse aging using integrated network analysis of transcriptomic and epigenomic changes during aging.

Aging is associated with widespread physiological changes, including skeletal muscle weakening, neuron system degeneration, hair loss, and skin wrinkling. Previous studies have identified numerous molecular biomarkers involved in these changes, but their regulatory mechanisms and functional repercussions remain elusive. In this study, we conducted next-generation sequencing of DNA methylation and RNA sequencing of blood samples from 51 healthy adults between 20 and 74 years of age and identified aging-related epigenetic and transcriptomic biomarkers. We also identified candidate molecular targets that can reversely regulate the transcriptomic biomarkers of aging by reconstructing a gene regulatory network model and performing signal flow analysis. For validation, we screened public experimental data including gene expression profiles in response to thousands of chemical perturbagens. Despite insufficient data on the binding targets of perturbagens and their modes of action, curcumin, which reversely regulated the biomarkers in the experimental dataset, was found to bind and inhibit JUN, which was identified as a candidate target via signal flow analysis. Collectively, our results demonstrate the utility of a network model for integrative analysis of omics data, which can help elucidate inter-omics regulatory mechanisms and develop therapeutic strategies against aging.

Hyperlactacidemia as a risk factor for intensive care unit-acquired weakness in critically ill adult patients.

INTRODUCTION/AIMS: Intensive care unit-acquired weakness (ICUAW) is a severe neuromuscular complication of critical illness. Serum lactate is a useful biomarker in critically ill patients. The relationship between serum lactate level and ICUAW remains controversial. This study evaluated whether hyperlactacidemia (lactate level >2 mmol/L) was an independent risk factor for ICUAW in critically ill adult patients. METHODS: An observational cohort study was performed in a general multidisciplinary intensive care unit (ICU). Sixty-eight consecutive adult critically ill patients without preexisting neuromuscular disease or a poor pre-ICU functional status whose length of ICU stay was 7 or more days were evaluated. Patients were screened daily for signs of awakening. Muscle strength assessment using the Medical Research Council score was performed on the first day a patient was considered awake. Patients with clinical muscle weakness were considered to have ICUAW. RESULTS: Among the 68 patients who achieved a satisfactory state of consciousness, the diagnosis of ICUAW was made in 30 patients (44.1%). After multivariate analysis, hyperlactacidemia (P = .02), Acute Physiology and Chronic Health Evaluation II score (P = .04), duration of mechanical ventilation (P = .02), and the use of norepinephrine (P = .04) were found to be significantly associated with the development of ICUAW in critically ill patients. DISCUSSION: This study shows a number of risk factors to be significantly associated with the development of ICUAW in critically ill adults. These factors should be considered when building early prediction models or designing prevention strategies for ICUAW in future studies.

How Much Vitamin D is Too Much? A Case Report and Review of the Literature.

BACKGROUND: The beneficial effects of vitamin D, together with the high prevalence of vitamin D deficiency, have led to an expanding use of vitamin D analogues. While inappropriate consumption is a recognized cause of harm, the determination of doses at which vitamin D becomes toxic remains elusive. CASE PRESENTATION: A 56-year woman was admitted to our Hospital following a 3-week history of nausea, vomiting, and muscle weakness. The patient had been assuming a very high dose of cholecalciferol for 20 months (cumulative 78,000,000UI, mean daily 130,000UI), as indicated by a non-- conventional protocol for multiple sclerosis. Before starting vitamin D integration, serum calcium and phosphorus levels were normal, while 25OH-vitamin D levels were very low (12.25 nmol/L). On admission, hypercalcemia (3.23 mmol/L) and acute kidney injury (eGFR 20 mL/min) were detected, associated with high concentrations of 25OH-vitamin D (920 nmol/L), confirming the suspicion of vitamin D intoxication. Vitamin D integration was stopped, and in a week, hypercalcemia normalized. It took about 6 months for renal function and 18 months for vitamin D values to go back to normal. CONCLUSION: This case confirms that vitamin D intoxication is possible, albeit with a high dose. The doses used in clinical practice are far lower than these and, therefore, intoxication rarely occurs even in those individuals whose baseline vitamin D serum levels have never been assessed. Repeated measurements of vitamin D are not necessary for patients under standard integrative therapy. However, patients and clinicians should be aware of the potential dangers of vitamin D overdose.

Prolonging the duration of cooling does not enhance recovery following a marathon.

Runners commonly utilize cryotherapy as part of their recovery strategy. Cryotherapy has been ineffective in mitigating signs and symptoms of muscle damage following marathon running and is limited by its duration of application. Phase change material (PCM) packs can prolong the duration of cooling. This study aimed to test the efficacy of prolonging the duration of cooling using PCM on perceptual recovery, neuromuscular function, and blood markers following a marathon run. Thirty participants completed a marathon run and were randomized to receive three hours of 15°C PCM treatment covering the quadriceps or recover without an intervention (control). Quadriceps soreness, strength, countermovement jump (CMJ) height, creatine kinase (CK), and high sensitivity C-reactive protein (hsCRP) were recorded at baseline, 24, 48, and 72 hours after the marathon. Following the marathon, strength decreased in both groups (P < .0001), with no difference between groups. Compared to baseline, strength was reduced 24 (P = .004) and 48 hours after the marathon (P = .008) in the control group, but only 24 hours (P = .028) in the PCM group. Soreness increased (P < .0001) and CMJ height decreased (P < .0001) in both groups, with no difference between groups. Compared to baseline, CMJ height was not reduced on any days in the PCM group but was reduced in the control group 24 (P < .0001) and 48 hours (P = .003) after the marathon. CK and hsCRP increased in both groups (P < .0001). Although the marathon run induced significant muscle damage, prolonging the duration of cooling using PCM did not accelerate the resolution of any dependent variables.

Endotypes of primary osteoarthritis identified by plasma metabolomics analysis.

OBJECTIVE: To identify endotypes of osteoarthritis (OA) by a metabolomics analysis. METHODS: Study participants included hip/knee OA patients and controls. Fasting plasma samples were metabolomically profiled. Common factor analysis and K-means clustering were applied to the metabolomics data to identify the endotypes of OA patients. Logistic regression was utilized to identify the most significant metabolites contributing to the endotypes. Clinical and epidemiological factors were examined in relation to the identified OA endotypes. RESULTS: Six hundred and fifteen primary OA patients and 237 controls were included. Among the 186 metabolites measured, 162 passed the quality control analysis. The 615 OA patients were classified in three clusters (A, 66; B, 200; and C, 349). Patients in cluster A had a significantly higher concentration of butyrylcarnitine (C4) than other clusters and controls (all P < 0.0002). Elevated C4 is thought to be related to muscle weakness and wasting. Patients in cluster B had a significantly lower arginine concentration than other clusters and controls (all P < 7.98 × 10-11). Cluster C patients had a significantly lower concentration of lysophosphatidylcholine (with palmitic acid), which is a pro-inflammatory bioactive compound, than other clusters and controls (P < 3.79 × 10-6). Further, cluster A had a higher BMI and prevalence of diabetes than other clusters (all P ≤ 0.0009), and also a higher prevalence of coronary heart disease than cluster C (P = 0.04). Cluster B had a higher prevalence of coronary heart disease than cluster C (P = 0.003) whereas cluster C had a higher prevalence of osteoporosis (P = 0.009). CONCLUSION: Our data suggest three possible clinically actionable endotypes in primary OA: muscle weakness, arginine deficit and low inflammatory OA.

Ectopic ACTH syndrome of different origin-Diagnostic approach and clinical outcome. Experience of one Clinical Centre.

PURPOSE: Ectopic Cushing Syndrome (EAS) is a rare condition responsible for about 5-20% of all Cushing syndrome cases. It increases the mortality of affected patients thus finding and removal of the ACTH-producing source allows for curing or reduction of symptoms and serum cortisol levels. The aim of this study is to present a 20-year experience in the diagnosis and clinical course of patients with EAS in a single Clinical Centre in Southern Poland as well as a comparison of clinical course and outcomes depending on the source of ectopic ACTH production-especially neuroendocrine tumors with other neoplasms. METHODS: Twenty-four patients were involved in the clinical study with EAS diagnosed at the Department of Endocrinology between years 2000 and 2018. The diagnosis of EAS was based on the clinical presentation, hypercortisolemia with high ACTH levels, high dose dexamethasone suppression test and/or corticotropin-releasing hormone tests. To find the source of ACTH various imaging studies were performed. RESULTS: Half of the patients were diagnosed with neuroendocrine tumors, whereby muscle weakness was the leading symptom. Typical cushingoid appearance was seen in merely a few patients, and weight loss was more common than weight gain. Patients with neuroendocrine tumors had significantly higher midnight cortisol levels than the rest of the group. Among patients with infections, we observed a significantly higher concentrations of cortisol 2400 levels in gastroenteropancreatic neuroendocrine tumors. Chromogranin A correlated significantly with potassium in patients with neuroendocrine tumors and there was a significant correlation between ACTH level and severity of hypokalemia. CONCLUSION: EAS is not common, but if it occurs it increases the mortality of patients; therefore, it should be taken into consideration in the case of coexistence of severe hypokalemia with hypertension and muscle weakness, especially when weight loss occurs. Because the diagnosis of gastroenteropancreatic neuroendocrine tumor worsens the prognosis-special attention should be paid to these patients.

Hydrocortisone mitigates ICU-AW by fine-tuning of muscle atrophic and hypertrophic signaling pathways in a sepsis model with limb immobilization.

AIMS: Intensive care unit-acquired weakness (ICU-AW) is a complex spectrum of disability that delays recovery of critically ill-immobilized patients with sepsis. Much discrepancy remain on the use of corticosteroids and their impact on muscle regeneration in critical illness management. Therefore, the aim of this study is to investigate whether hydrocortisone (HCT) modulates muscle mass turnover in ICU-AW induced by sepsis with limb immobilization (SI). MAIN METHODS: Sepsis by cecal ligation puncture (CLP) with forelimb-immobilization were performed in rats. The study consisted of four groups: Sham (left forelimb-immobilization), Sham HCT (left forelimb-immobilization + HCT), SI (CLP + left forelimb-immobilization) and SI HCT (CLP + left forelimb-immobilization + HCT). Motor force, blood and muscle sampling were assessed. KEY FINDINGS: HCT prevented body weight loss associated with SI and attenuated systemic and muscular inflammation. Besides, myosin was restituted in SI HCT group in conjunction to muscle mass and strength restoration. Pro-hypertrophic calcineurin (PP2B-Aß) and nuclear factor of activated T-cells C3 (NFATc3) but not protein kinase B (Akt) were re-activated by HCT. Finally, pro-atrophic extracellular signal-regulated kinases (ERK1/2) and p38 mitogen-activated protein kinases (p38) but not nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) were inhibited in SI HCT group. SIGNIFICANCE: This study unravels new molecular events thought to control muscle protein synthesis in ICU-AW induced by sepsis and limb immobilization. HCT has a potential to fine-tune muscle-signaling pathways and to reduce the negative outcomes of ICU-AW.

Cytokines and inflammatory mediators as promising markers of polymyositis/dermatomyositis.

PURPOSE OF REVIEW: Idiopathic inflammatory myopathies (IIMs), known also as myositis, represent challenging group of heterogeneous muscle disorders characterized by symmetric proximal muscle weakness and evidence of muscle inflammation. The purpose of this review is to provide important updates on cytokines and inflammatory mediators related to myositis. RECENT FINDINGS: In the past 5 years, multiple studies brought a fresh insight into the pathogenesis of myositis by introducing new factors or further characterizing the role of the well established mediators in myositis. Among the mediators reviewed in this article, special attention was paid to interferons, C-X-C motif chemokine ligand 10, interleukin-18 and the IL23/Th17 axis. Some of the recent work has also focused on the nontraditional cytokines, such as adipokines, myokines, S100 proteins, High Mobility Group Box 1 or B-cell activating factor and on several anti-inflammatory mediators. Moreover, microRNAs and their potential to reflect the disease activity or to regulate the inflammatory processes in myositis have recently been subject of intensive investigation. Some of the above-mentioned mediators have been proposed as promising clinical biomarkers or therapeutic targets for myositis. SUMMARY: Several recent studies contributed to a better understanding of the pathogenesis of myositis and highlighted the clinical significance of certain inflammatory mediators. Application of these new findings may help to develop innovative approaches for patients' phenotyping, disease activity monitoring and potentially novel therapies.

Sarcopenia in female patients with Alzheimer's disease are more likely to have lower levels of haemoglobin and 25-hydroxyvitamin D.

AIM: Few studies have investigated sarcopenia in patients with cognitive impairment. However, identifying the characteristics and factors associated with sarcopenia in these patients may help to decrease the risk of falls, prevent disabilities, and maintain an independent life, all of which can affect the quality of life of both patient and caregiver. Therefore, the aim of this study was to investigate associated factors of sarcopenia in patients with mild to moderate Alzheimer's disease. METHODS: This cross-sectional study enrolled 125 outpatients aged 65 to 89 years (mean age 79.5 ± 7.9 years) from January 2018 to December 2018. In addition to demographic characteristics, cognitive status, depressive mood, activities of daily living, body mass index (BMI), handgrip strength, gait speed, muscle mass, and serum levels of 25-hydroxyvitamin D (Vit D), haemoglobin (Hb), albumin and creatinine were assessed. Sarcopenia was defined based on the presence of low muscle mass and either low muscle strength or low physical performance. RESULTS: Overall, 29.6% of the patients had sarcopenia. The patients with sarcopenia were mostly male, significantly older, and had a lower BMI and lower levels of Vit D. The female patients with sarcopenia were more likely to have lower levels of Hb. Multiple logistic regression showed that sarcopenia was associated with BMI in both genders. The level of Vit D was associated with sarcopenia in the female patients, whereas age was associated with sarcopenia in the male patients. CONCLUSIONS: A low BMI may be a dementia-related risk factor for sarcopenia. The female patients with sarcopenia were more likely to have lower levels of Hb and Vit D. There may be different risk profiles for sarcopenia in men and women with Alzheimer's disease. Further studies are needed to devise different nutritional support for muscle weakness in patients with cognitive decline by gender.

GDF15 Plasma Level Is Inversely Associated With Level of Physical Activity and Correlates With Markers of Inflammation and Muscle Weakness.

Growth differentiation factor 15 (GDF15) is a stress molecule produced in response to mitochondrial, metabolic and inflammatory stress with a number of beneficial effects on metabolism. However, at the level of skeletal muscle it is still unclear whether GDF15 is beneficial or detrimental. The aim of the study was to analyse the levels of circulating GDF15 in people of different age, characterized by different level of physical activity and to seek for correlation with hematological parameters related to inflammation. The plasma concentration of GDF15 was determined in a total of 228 subjects in the age range from 18 to 83 years. These subjects were recruited and divided into three different groups based on the level of physical activity: inactive patients with lower limb mobility impairment, active subjects represented by amateur endurance cyclists, and healthy controls taken from the general population. Cyclists were sampled before and after a strenuous physical bout (long distance cycling race). The plasma levels of GDF15 increase with age and are inversely associated with active lifestyle. In particular, at any age, circulating GDF15 is significantly higher in inactive patients and significantly lower in active people, such as cyclists before the race, with respect to control subjects. However, the strenuous physical exercise causes in cyclists a dramatic increase of GDF15 plasma levels, that after the race are similar to that of patients. Moreover, GDF15 plasma levels significantly correlate with quadriceps torque in patients and with the number of total leukocytes, neutrophils and lymphocytes in both cyclists (before and after race) and patients. Taken together, our data indicate that GDF15 is associated with decreased muscle performance and increased inflammation.

[Muscle weakness and CK elevation: is it myositis?] / Muskelschwäche und CK­Erhöhung: Ist es immer eine Myositis?

Rheumatologists are often confronted by patients with muscle weakness and elevated creatine kinase (CK) levels. Myositis cannot always be determined to be the cause of the complaints. This article presents two cases from our hospital where the diagnosis could only be determined by muscle biopsy. In the first case the patient presented with muscle weakness, pathological weight loss and a significant increase in CK levels. A muscle biopsy revealed an immune-mediated necrotizing myopathy (IMNM) caused by anti-3-hydroxy-3-methyl-gulatryl-CoA reductase (HMG-CoA reductase) autoantibodies due to the intake of statins. The second patient presented with cramp-like and burning muscle pain and weakness of the extremities without a relevant increase in CK level. Myoadenylate deaminase deficiency was also detected by muscle biopsy, and further confirmed by genetic testing.

Associations of Preoperative Irisin Levels of Paired Cerebrospinal Fluid and Plasma with Physical Dysfunction and Muscle Wasting Severity in Residents of Surgery Wards.

BACKGROUND: Myokine Irisin has been proposed to regulate metabolic homeostasis, which is related to chronic diseases or physical activity. However, whether irisin levels in paired cerebrospinal fruid (CSF), plasma and their ratio of inpatients, could use as biomarkers, and be independently related to the varying physical dysfunction, muscle wasting severity and chronic diseases with varying severe degrees, remain largely elusive. METHODS: We conducted an observational study to assess the independent associations between irisin levels in paired cerebrospinal fruid (CSF), plasma and their ratio, and the independence in activities of daily life (ADLs), muscle wasting severity and chronic diseases with varying severe degrees among elderly Chinese in-patient subjects. RESULTS: Among 217 inpatients in surgery wards with a mean age of 68.07 years (±15.94years), 31.3% of women and 68.7% of men were included in the study. Bivariate correlation analysis showed that Log transformed CSF and plasma irisin levels and their ratio were potential associated with age, fat%, muscle wasting time, ADLs, number of multimorbidity, the severity of bone mass loss and anemia. Regression models analysis indicated that CSF and plasma irisin levels and their ratio in inpatient individuals were independently associated with the independence in ADLs. Plasma irisin levels were independently related to the change of muscle wasting use. CONCLUSIONS: Collectively, the evaluation of paired plasma and CSF irisin levels, and their ratio in in-patient individuals is intriguing candidates for the susceptibility of the independence in ADLs. Plasma irisin levels were positively associated with indepedence in ADLs, negatively related to muscle wasting severity, and could use as biomarkers for muscle wasting severity.

Utility of Plasma GDF-15 for Diagnosis and Prognosis Assessment of ICU-Acquired Weakness in Mechanically Ventilated Patients: Prospective Observational Study.

OBJECTIVE: To identify the clinical correlations between plasma growth differentiation factor-15 (GDF-15), skeletal muscle function, and acute muscle wasting in ICU patients with mechanical ventilation. In addition, to investigate its diagnostic value for ICU-acquired weakness (ICU-AW) and its predictive value for 90-day survival in mechanically ventilated patients. METHODS: 95 patients with acute respiratory failure, who required mechanical ventilation therapy, were randomly selected among hospitalized patients from June 2017 to January 2019. The plasma GDF-15 level was detected by ELISA, the rectus femoris cross-sectional area (RFcsa) was measured by ultrasound, and the patient's muscle strength was assessed using the British Medical Research Council (MRC) muscle strength score on day 1, day 4, and day 7. Patients were divided into an ICU-AW group and a non-ICU-AW group according to their MRC-score on the 7th day. The differences in plasma GDF-15 level, MRC-score, and RFcsa between the two groups were compared on the 1st, 4th, and 7th day after being admitted to the ICU. Then, the correlations between plasma GDF-15 level, RFcsa loss, and MRC-score on day 7 were investigated. The receiver operating characteristic curve (ROC) was used to analyze the plasma GDF-15 level, RFcsa loss, and % decrease in RFcsa on the 7th day to the diagnosis of ICU-AW in mechanically ventilated patients. Moreover, the predictive value of GDF-15 on the 90-day survival status of patients was assessed using patient survival curves. RESULTS: Based on whether the 7th day MRC-score was <48, 50 cases were included in the ICU-AW group and 45 cases in the non-ICU-AW group. The length of mechanical ventilation, ICU length of stay, and hospital length of stay were significantly longer in the ICU-AW group than in the non-ICU-AW group (all P < 0.05), while the other baseline indicators were not statistically significant between the two groups. As the treatment time increased, the plasma GDF-15 level was significantly increased, the ICU-AW group demonstrated a significant decreasing trend in the MRC-score and RFcsa, while no significant changes were found in the non-ICU-AW group. In the ICU-AW group, the plasma GDF-15 level was significantly higher than that in the non-ICU-AW group, while the RFcsa and the MRC-score were significantly lower than those in the non-ICU-AW group (GDF-15 (pg/ml): 2542.44 ± 629.38 vs. 1542.86 ± 502.86; RFcsa (cm2): 2.04 ± 0.64 vs. 2.34 ± 0.61; MRC-score: 41.22 ± 3.42 vs. 51.42 ± 2.72, all P < 0.05), while the other baseline indicators were not statistically significant between the two groups. As the treatment time increased, the plasma GDF-15 level was significantly increased, the ICU-AW group demonstrated a significant decreasing trend in the MRC-score and RFcsa, while no significant changes were found in the non-ICU-AW group. In the ICU-AW group, the plasma GDF-15 level was significantly higher than that in the non-ICU-AW group, while the RFcsa and the MRC-score were significantly lower than those in the non-ICU-AW group (GDF-15 (pg/ml): 2542.44 ± 629.38 vs. 1542.86 ± 502.86; RFcsa (cm2): 2.04 ± 0.64 vs. 2.34 ± 0.61; MRC-score: 41.22 ± 3.42 vs. 51.42 ± 2.72, all r = -0.60), while it was significantly positively correlated with the RFcsa loss (r = -0.60), while it was significantly positively correlated with the RFcsa loss (r = -0.60), while it was significantly positively correlated with the RFcsa loss (r = -0.60), while it was significantly positively correlated with the RFcsa loss (P < 0.05), while the other baseline indicators were not statistically significant between the two groups. As the treatment time increased, the plasma GDF-15 level was significantly increased, the ICU-AW group demonstrated a significant decreasing trend in the MRC-score and RFcsa, while no significant changes were found in the non-ICU-AW group. In the ICU-AW group, the plasma GDF-15 level was significantly higher than that in the non-ICU-AW group, while the RFcsa and the MRC-score were significantly lower than those in the non-ICU-AW group (GDF-15 (pg/ml): 2542.44 ± 629.38 vs. 1542.86 ± 502.86; RFcsa (cm2): 2.04 ± 0.64 vs. 2.34 ± 0.61; MRC-score: 41.22 ± 3.42 vs. 51.42 ± 2.72, all P < 0.05), while the other baseline indicators were not statistically significant between the two groups. As the treatment time increased, the plasma GDF-15 level was significantly increased, the ICU-AW group demonstrated a significant decreasing trend in the MRC-score and RFcsa, while no significant changes were found in the non-ICU-AW group. In the ICU-AW group, the plasma GDF-15 level was significantly higher than that in the non-ICU-AW group, while the RFcsa and the MRC-score were significantly lower than those in the non-ICU-AW group (GDF-15 (pg/ml): 2542.44 ± 629.38 vs. 1542.86 ± 502.86; RFcsa (cm2): 2.04 ± 0.64 vs. 2.34 ± 0.61; MRC-score: 41.22 ± 3.42 vs. 51.42 ± 2.72, all P < 0.05), while the other baseline indicators were not statistically significant between the two groups. As the treatment time increased, the plasma GDF-15 level was significantly increased, the ICU-AW group demonstrated a significant decreasing trend in the MRC-score and RFcsa, while no significant changes were found in the non-ICU-AW group. In the ICU-AW group, the plasma GDF-15 level was significantly higher than that in the non-ICU-AW group, while the RFcsa and the MRC-score were significantly lower than those in the non-ICU-AW group (GDF-15 (pg/ml): 2542.44 ± 629.38 vs. 1542.86 ± 502.86; RFcsa (cm2): 2.04 ± 0.64 vs. 2.34 ± 0.61; MRC-score: 41.22 ± 3.42 vs. 51.42 ± 2.72, all. CONCLUSION: The plasma GDF-15 concentration level was significantly associated with skeletal muscle function and muscle wasting on day 7 in ICU patients with mechanical ventilation. Therefore, it can be concluded that the plasma GDF-15 level on the 7th day has a high diagnostic yield for ICU-acquired muscle weakness, and it can predict the 90-day survival status of ICU mechanically ventilated patients.

Elderly woman with subacute lower limb weakness and rapid systemic decline.

A 74-year-old woman developed bilateral leg weakness, with fluctuating cognitive and systemic symptoms that progressed despite treatment. Her diagnosis was confirmed at autopsy. Her case was discussed at the Edinburgh Clinical Neurology Course 2019 Clinicopathological Conference.

Association between serum n-3 polyunsaturated fatty acids and quadriceps weakness immediately after total knee arthroplasty.

OBJECTIVES: Quadriceps weakness (QW) following total knee arthroplasty (TKA) can be elicited by tourniquet-induced ischaemia reperfusion (IR), which causes a vigorous acute inflammatory response. Dietary n-3 polyunsaturated fatty acids (PUFA) are important determinants of organ and tissue protection from IR. This study aimed to examine the association between serum n-3 PUFA levels and QW, knee pain, and knee swelling immediately after TKA. METHODS: A total of 32 patients who underwent unilateral TKA participated in this prospective study. On Postoperative Day 1, serum n-3 PUFA (eicosapentaenoic acid and docosahexaenoic acid) levels were measured. Preoperatively and on Postoperative Day 4, quadriceps strength, knee pain during quadriceps testing, and knee circumference were measured. QW, knee pain, and knee swelling were defined as changes in quadriceps strength, knee pain during quadriceps testing, and knee circumference, respectively, between the preoperative to the postoperative measurement. RESULTS: Mean serum n-3 PUFA levels were 192 µg/mL (standard deviation, 58 µg/mL) on Postoperative Day 1. All measured variables changed significantly between the preoperative and the postoperative measurement time-points (P <0.01). Quadriceps strength decreased from 1.2 to 0.4 Nm/kg (QW = -65%). Knee pain during quadriceps testing increased from 1.1 to 6.0 (knee pain = 4.0). Knee circumference increased from 40 to 44 cm (knee swelling = 10%). Multivariate analysis showed that lower serum n-3 PUFA levels were independently associated with an increased QW after adjusting for the Kellgren-Lawrence grade and the tourniquet time (P = 0.04). No significant relationship was observed between serum n-3 PUFA levels and knee pain or knee swelling. CONCLUSION: Higher serum n-3 PUFA are independently associated with a lower increase in the QW immediately after TKA.

Creatinine-to-cystatin C ratio as a marker of skeletal muscle mass in older adults: J-SHIPP study.

BACKGROUND: Sarcopenia increases mortality risk in older adults. Loss of skeletal muscle mass is a cardinal feature of sarcopenia. The creatinine-to-cystatin C ratio (CCR) has been suggested as a marker of muscle mass. The present study investigated the usefulness of CCR in discriminating the risk of low muscle mass and weak muscle strength in an elderly population. METHODS: The present cross-sectional study included 1,329 apparently healthy community residents aged 60 years or older. The cross-sectional area (CSA) of muscle in the mid-thigh was measured using computed tomography. Clinical data recorded at routine medical check-ups were obtained from each participant's medical record. RESULTS: Mean muscle CSA was 109 ± 24 cm2. CCR by quartiles according to sex was strongly associated with muscle CSA (Q1: 104 ± 22, Q2: 108 ± 24, Q3: 110 ± 23, and Q4: 114 ± 25 cm2, F = 10.38, P < 0.001). This association was independent of major covariates (Q1: reference, Q2: ß = 0.06, P < 0.001, Q3: ß = 0.10, P < 0.001, and Q4: ß = 0.17, P < 0.001) even in a sex-separated analysis. Although creatinine alone was independently associated with muscle CSA (F = 5.81, P < 0.001), the association was weaker than that of CCR, particularly in the individuals with renal functional decline. Also, CCR was associated with grip strength independently of muscle CSA. CONCLUSION: CCR was a simple marker of low muscle mass and weak muscle strength in older community-dwelling adults.