Circulating myostatin as a biomarker of muscle mass and strength in individuals with cancer or obesity.

BACKGROUND & AIMS: Our study aims to determine whether myostatin (MSTN) is associated with muscle mass and strength in individuals with cancer or obesity, as well as with cancer cachexia (CC) or sarcopenic obesity (SO). METHODS: The ACTICA study included individuals with CC (n = 70) or without CC (NC, n = 73). The MYDIASECRET study included individuals with obesity evaluated before (T0) and 3 months (T3) after bariatric surgery (n = 62). Body composition was assessed using bioelectrical impedance analysis (BIA). Skeletal muscle mass (SMM) and appendicular SMM (ASMM) were calculated from Janssen's and Sergi's equations, respectively, and expressed as indexes (SMMI and ASMMI). Handgrip strength (HGS) was assessed using a Jamar hand-held dynamometer. MSTN plasma levels were measured using ELISA. Spearman's coefficient was used to correlate MSTN with muscle mass and strength. Receiver operating characteristic (ROC) curve analysis was performed to identify an optimal MSTN cutoff level for the prediction of CC or SO. RESULTS: In the ACTICA study, muscle mass and strength were lower in CC individuals than in NC individuals (SMMI: 8.0 kg/m2vs 9.0 kg/m2, p = 0.004; ASMMI: 6.2 kg/m2vs 7.2 kg/m2, p < 0.001; HGS: 28 kg vs 38 kg, p < 0.001). MSTN was also lower in CC individuals than in NC individuals (1434 pg/mL vs 2149 pg/mL, p < 0.001). Muscle mass and strength were positively correlated with MSTN (SMMI: R = 0.500, p < 0.001; ASMMI: R = 0.479, p < 0.001; HGS: R = 0.495, p < 0.001). ROC curve analysis showed a MSTN cutoff level of 1548 pg/mL (AUC 0.684, sensitivity 57%, specificity 75%, p < 0.001) for the prediction of CC. In the MYDIASECRET study, muscle mass and strength were reduced at T3 (SMMI: -8%, p < 0.001; ASMMI: -12%, p < 0.001; HGS: -6%, p = 0.005). MSTN was also reduced at T3 (1773 pg/mL vs 2582 pg/mL, p < 0.001). Muscle mass and strength were positively correlated with MSTN at T0 and T3 (SMMI-T0: R = 0.388, p = 0.002; SMMI-T3: R = 0.435, p < 0.001; HGS-T0: R = 0.337, p = 0.007; HGS-T3: R = 0.313, p = 0.013). ROC curve analysis showed a MSTN cutoff level of 4225 pg/mL (AUC 0.835, sensitivity 98%, specificity 100%, p = 0.014) for the prediction of SO at T3. CONCLUSIONS: MSTN is positively correlated with muscle mass and strength in individuals with cancer or obesity, suggesting its potential use as a biomarker of muscle mass and strength. The ROC curve analysis suggests the potential use of MSTN as a screening tool for CC and SO.

Mortality-related risk factors of inpatients with diabetes and COVID-19: A multicenter retrospective study in Belgium.

BACKGROUND AND AIMS: We describe mortality-related risk factors of inpatients with diabetes and coronavirus disease 2019 (COVID-19) in Belgium. METHODS: We conducted a multicenter retrospective study from March to May, 2020, in 8 Belgian centers. Data on admission of patients with diabetes and COVID-19 were collected. Survivors were compared to non-survivors to identify prognostic risk factors for in-hospital death using multivariate analysis in both the total population and in the subgroup of patients admitted in the intensive care unit (ICU). RESULTS: The study included 375 patients. The mortality rate was 26.4% (99/375) in the total population and 40% (27/67) in the ICU. Multivariate analysis identified older age (HR 1.05 [CI 1.03-1.07], P<0.0001) and male gender (HR 2.01 [1.31-3.07], P=0.0013) as main independent risk factors for in-hospital death in the total population. Metformin (HR 0.51 [0.34-0.78], P=0.0018) and renin-angiotensin-aldosterone system blockers (HR 0.56 [0.36-0.86], P=0.0088) use before admission were independent protective factors. In the ICU, chronic kidney disease (CKD) was identified as an independent risk factor for death (HR 4.96 [2.14-11.5], P<0.001). CONCLUSION: In-hospital mortality due to the first wave of COVID-19 pandemic in Belgium was high in patients with diabetes. We found that advanced age and male gender were independent risk factors for in-hospital death. We also showed that metformin use before admission was associated with a significant reduction of COVID-19-related in-hospital mortality. Finally, we showed that CKD is a COVID-19-related mortality risk factor in patients with diabetes admitted in the ICU.

Identification of myokines susceptible to improve glucose homeostasis after bariatric surgery.

IMPORTANCE AND OBJECTIVE: The identification of myokines susceptible to improve glucose homeostasis following bariatric surgery could lead to new therapeutic approaches for type 2 diabetes. METHODS: Changes in the homeostasis model assessment (HOMA) test were assessed in patients before and 3 months after bariatric surgery. Changes in myokines expression and circulating levels were assessed using real-time quantitative polymerase chain reaction (RT-qPCR) and enzyme-linked immunosorbent assay (ELISA). Myokines known to regulate glucose homeostasis were identified using literature (targeted study) and putative myokines using RNA-sequencing (untargeted study). A linear regression analysis adjusted for age and sex was used to search for associations between changes in the HOMA test and changes in myokines. RESULTS: In the targeted study, brain-derived neurotrophic factor (BDNF) expression was upregulated (+30%, P = .006) while BDNF circulating levels were decreased (-12%, P = .001). Upregulated BDNF expression was associated with decreased HOMA of insulin resistance (HOMA-IR) (adjusted estimate [95% confidence interval {CI}]: -0.51 [-0.88 to -0.13], P = .010). Decreased BDNF serum levels were associated with decreased HOMA of beta-cell function (HOMA-B) (adjusted estimate [95% CI] = 0.002 [0.00002-0.0031], P = .046). In the untargeted study, upregulated putative myokines included XYLT1 (+64%, P < .001), LGR5 (+57, P< .001), and SPINK5 (+46%, P < .001). Upregulated LGR5 was associated with decreased HOMA-IR (adjusted estimate [95% CI] = -0.50 [-0.86 to -0.13], P = .009). Upregulated XYLT1 and SPINK5 were associated with increased HOMA of insulin sensitivity (HOMA-S) (respectively, adjusted estimate [95% CI] = 109.1 [28.5-189.8], P = .009 and 16.5 [0.87-32.19], P = .039). CONCLUSIONS: Improved glucose homeostasis following bariatric surgery is associated with changes in myokines expression and circulating levels. In particular, upregulation of BDNF, XYLT1, SPINK5, and LGR5 is associated with improved insulin sensitivity. These results suggest that these myokines could contribute to improved glucose homeostasis following bariatric surgery. STUDY REGISTRATION: NCT03341793 on ClinicalTrials.gov (https://clinicaltrials.gov/).

Prevalence, Characteristics, and Prognosis of Peripheral Arterial Disease in Patients With Diabetic Charcot Foot.

Charcot foot (CF) is a rare complication of diabetes associated with foot deformities and foot ulcers. Peripheral arterial disease (PAD) is a factor of poor prognosis in patients with diabetic foot ulcers (DFUs). However, PAD has infrequently been studied in CF. We aimed to determine the prevalence, the characteristics and the prognosis of PAD in a large group of patients with diabetic CF. We retrospectively compared 56 patients with diabetic CF to 116 patients with diabetic foot without CF. The prevalence of PAD in patients with CF was 66.1%. Compared to patients without CF, patients with CF had similar risks to have PAD (OR 0.98, 95%CI 0.50-1.94, p= .97) and neuro-ischemic DFUs (OR 1.19, 95%CI 0.57-2.49, p= .65), more risk to have lesions of distal arteries (OR 4.17, 95%CI 1.76-9.94, p= .001) and less risk to need revascularization (OR 0.14, 95%CI 0.06-0.36, p< .001). In patients with CF, PAD was strongly predicted by DFUs (OR 24.55, 95%CI 1.80-334.43, p= .016) and coronary artery disease (OR 17.11, 95%CI 1.75-167.43, p =.015). Survival rate and limb salvage rate in patients with CF were not worsened by PAD and by neuro-ischemic DFUs, respectively. In conclusion, we show that PAD should not be overlooked in patients with diabetic CF, especially in those having DFUs or coronary artery disease. PAD in patients with CF differed from that of patients without CF since it predominated in distal arteries and required less often revascularization.

Clinical characteristics and short-term prognosis of in-patients with diabetes and COVID-19: A retrospective study from an academic center in Belgium.

BACKGROUND AND AIMS: We describe the characteristics and short-term prognosis of in-patients with diabetes and COVID-19 admitted to a Belgian academic care center. METHODS: We retrospectively reviewed the data on admission from patients with known or newly-diagnosed diabetes and confirmed COVID-19. First, survivors were compared to non-survivors to study the predictive factors of in-hospital death in patients with diabetes. Secondly, diabetic patients with SARS-CoV-2 pneumonia were matched for age and sex with non-diabetic patients with SARS-CoV-2 pneumonia, to study the prognosis and predictive factors of in-hospital death related to diabetes. RESULTS: Seventy-three diabetic patients were included. Mean age was 69 (±14) years. Women accounted for 52%. Most patients had type 2 diabetes (89.0%), long-term complications of hyperglycemia (59.1%), and hypertension (80.8%). The case-fatality rate (CFR) was 15%. Non-survivors had more severe pneumonia based on imaging (p 0.029) and were less often treated with metformin (p 0.036). In patients with SARS-CoV-2 pneumonia, CFR was 15.6% in diabetic (n = 64) and 25.0% in non-diabetic patients (n = 128), the difference being non-significant (p 0.194). Predictive factors of in-hospital death were elevated white blood cells count (HR 9.4, CI 1.50-58.8, p 0.016) and severe pneumonia on imaging (HR 25.0, CI 1.34-466, p 0.031) in diabetic patients, and cognitive impairment (HR 5.80, CI 1.61-20.9, p 0.007) and cardiovascular disease (HR 5.63, CI 1.54-20.6, p 0.009) in non-diabetic patients. CONCLUSION: In this monocentric cohort from Belgium, diabetic in-patients with COVID-19 had mostly type 2 diabetes, prevalent hyperglycemia-related vascular complications and comorbidities including hypertension. In this cohort, the CFR was not statistically different between patients with and without diabetes.

COVID-19 in diabetic patients: Related risks and specifics of management.

Diabetes is among the most frequently reported comorbidities in patients infected with COVID-19. According to current data, diabetic patients do not appear to be at increased risk of contracting SARS-CoV-2 compared to the general population. On the other hand, diabetes is a risk factor for developing severe and critical forms of COVID-19, the latter requiring admission to an intensive care unit and/or use of invasive mechanical ventilation, with high mortality rates. The characteristics of diabetic patients at risk for developing severe and critical forms of COVID-19, as well as the prognostic impact of diabetes on the course of COVID-19, are under current investigation. Obesity, the main risk factor for incident type 2 diabetes, is more common in patients with critical forms of COVID-19 requiring invasive mechanical ventilation. On the other hand, COVID-19 is usually associated with poor glycemic control and a higher risk of ketoacidosis in diabetic patients. There are currently no recommendations in favour of discontinuing antihypertensive medications that interact with the renin-angiotensin-aldosterone system. Metformin and SGLT2 inhibitors should be discontinued in patients with severe forms of COVID-19 owing to the risks of lactic acidosis and ketoacidosis. Finally, we advise for systematic screening for (pre)diabetes in patients with proven COVID-19 infection.

Mortality in patients with high risk Staphylococcus aureus bacteremia undergoing or not PET-CT: A single center experience.

BACKGROUND: Staphylococcus aureus bacteremia (SAB) is associated with significant morbidity and mortality. Previous studies had shown that PET/CT can be helpfull in the management of SAB, leading to reduction of mortality. Factors associated with increased or reduced mortality are not well known. Our objective was to analyze mortality in high risk SAB patients undergoing PET/CT and to identify factors associated with mortality rate. MATERIALS AND METHODS: We performed a retrospective study and reviewed all cases of high risk adult SAB between 2014 and 2017. We analyzed medical records and mortality at 30 days and 90 days and 1 year. RESULTS: A total of 102 patients were included in whom 48 undergone PET/CT. Metastatic foci was identified in 45.8% of cases (22/48). The overall mortality rate was 31.4% (32/102). The mortality rate was 16.6% (8/48) and 44.4% (24/54) in patients undergoing or not PET/CT respectively (P = 0.002). There was a signicantly difference in mortality rate at 30 days (P = 0.001), 90 days (P = 0.004) and one at 1 year (P = 0.002) between patients undergoing or not PET/CT respectively. In multivariate analysis only 18-FDGPET/CT, kidney failure and bacteremia of unknown origin were the 3 mains factors modifying mortality in patients with high risk SAB. CONCLUSION: In our study mortality rate was reduced in high risk SAB patients undergoing PET/CT. kidney failure and bacteremia of unknown origin were other factors associtated with high mortality. Our study confirm that PET/CT is a usefull tool in the management of SAB.