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.

Intraoperative Ketorolac and Outcomes after Ovarian Cancer Surgery.

INTRODUCTION: Surgery is the cornerstone of ovarian cancer treatment. However, surgery and perioperative inflammation have been described as potentially pro-metastagenic. In various animal models and other human cancers, intraoperative administration of non-steroidal anti-inflammatory drugs (NSAIDs) appears to have a positive impact on patient outcomes. MATERIALS AND METHODS: In this unicentric retrospective study, we provide an exploratory analysis of the safety and potential benefit of intraoperative administration of ketorolac on the outcome of patients undergoing surgery for ovarian cancer. The study population included all patients who were given a diagnosis of ovarian, fallopian tube or peritoneal cancer by the multidisciplinary oncology committee (MOC) of the Cliniques universitaires Saint-Luc between 2015 and 2020. RESULTS: We included 166 patients in our analyses, with a median follow-up of 21.8 months. Both progression-free survival and overall survival were superior in patients who received an intraoperative injection of ketorolac (34.4 months of progression-free survival in the ketorolac group versus 21.5 months in the non-ketorolac group (p = 0.002), and median overall survival was not reached in either group but there was significantly higher survival in the ketorolac group (p = 0.004)). We also performed subgroup analyses to minimise bias due to imbalance between groups on factors that could influence patient survival, and the group of patients receiving ketorolac systematically showed a better outcome. Uni- and multivariate analyses confirmed that administration of ketorolac intraoperatively was associated with better progression-free survival (HR = 0.47 on univariate analysis and 0.43 on multivariate analysis, p = 0.003 and 0.023, respectively). In terms of complications, there were no differences between the two groups, either intraoperatively or postoperatively. CONCLUSION: Our study has shown a favourable association between the use of ketorolac during surgery and the postoperative progression of ovarian cancer in a group of 166 patients, without any rise in intra- or postoperative complications. These encouraging results point to the need for a prospective study to confirm the benefit of intraoperative administration of ketorolac in ovarian cancer surgery.

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/).

Capacity building at points of entry during COVID-19 pandemic: harmonising training curriculum for Economic Community of West African States.

This paper describes the process for developing, validating and disseminating through a train-the-trainer (TOT) event a standardised curriculum for public health capacity building for points of entry (POE) staff across the 15-member state Economic Community of West African States (ECOWAS) that reflects both international standards and national guidelines.A five-phase process was used in developing the curriculum: phase (1) assessment of existing materials developed by the US Centers for Disease Control and Prevention (CDC), Africa CDC and the West African Economic and Monetary Union, (2) design of retained and new, harmonised content, (3) validation by the national leadership to produce final content, (4) implementation of the harmonised curriculum during a regional TOT, and (5) evaluation of the curriculum.Of the nine modules assessed in English and French, the technical team agreed to retain six harmonised modules providing materials for 10 days of intensive training. Following the TOT, most participants (n=28/30, 93.3%) indicated that the International Health Regulations and emergency management modules were relevant to their work and 96.7% (n=29/30) reported that the training should be cascaded to POE staff in their countries.The ECOWAS harmonised POE curriculum provides a set of training materials and expectations for national port health and POE staff to use across the region. This initiative contributes to reducing the effort required by countries to identify emergency preparedness and response capacity-building tools for border health systems in the Member States in a highly connected region.

Use of thyroid hormones in hypothyroid and euthyroid patients: a THESIS* survey of Belgian specialists *THESIS: treatment of hypothyroidism in Europe by specialists: an international survey.

BACKGROUND: Hypothyroidism is a topic that continues to provoke debate and controversy with regards to specific indications, type of thyroid hormone substitution and efficacy. We investigated the use of thyroid hormones in clinical practice in Belgium, a country where currently only levothyroxine (LT4) tablet formulations are available. METHOD: Members of the Belgian Endocrine Society were invited to respond to an online questionnaire. Results were compared with those from other THESIS surveys. RESULTS: Eighty (50%) of the invited 160 individuals, completed the questionnaire. LT4 was the first treatment of choice for all respondents. As secondary choice, some also prescribed liothyronine (LT3) and LT4 + LT3 combinations (2 and 7 respondents, respectively). Besides hypothyroidism, 34 and 50% of respondents used thyroid hormones for infertile euthyroid TPOAb positive women and the treatment of a growing non-toxic goiter, respectively. Had alternative formulations of LT4 to tablets been available (soft gel or liquid L-T4), 2 out of 80 (2.5%) participants would consider them for patients achieving biochemical euthyroidism but remaining symptomatic. This proportion was higher in case of unexplained poor biochemical control of hypothyroidism (13.5%) and in patients with celiac disease or malabsorption or interfering drugs (10%). In symptomatic euthyroid patients, 20% of respondents would try combined LT4 + LT3 treatment. Psychosocial factors were highlighted as the main contributors to persistent symptoms. CONCLUSIONS: LT4 tablets is the preferred treatment for hypothyroidism in Belgium. A minority of the respondents would try combined LT4 + LT3 in symptomatic but biochemically euthyroid patients. Thyroid hormones are prescribed for euthyroid infertile women with thyroid autoimmunity and patients with non-toxic goiter, a tendency noted in other European countries, despite current evidence of lack of benefit.

Early Melanoma Detection in Primary Care: Clinical Recognition of Melanoma is Not Enough, One Must Also Learn the Basics.

To improve early melanoma detection, educational programs have been developed for general practitioners (GPs). This study aimed to determine whether the adjunct of teaching basic knowledge of pigmented skin lesions (PSL) to the training in melanoma diagnosis improves the GPs' diagnostic accuracy of melanoma. An interventional prospective study was conducted over a 3-month period where GPs attended a 2-h training course. The 1st session taught clinical melanoma recognition and the 2nd session instructed basic knowledge of PSL. Prior to training, after the 1st, and after the 2nd session, GPs were asked to select the malignant or benign nature of 15 clinical images associated to their clinical history. In total, 56 GPs participated in this study. The number of GPs identifying correctly ≥ 50% of the melanomas increased the most after the 1st session from 15 (26.8%; CI = (15.2; 38.4)) to 44 (78.6%; CI = (67.8; 89.3)) GPs (P < 0.001). The number of GPs correctly identifying ≥ 50% of the benign PSL only increased after completing the entire training, going from 10 (17.9%; CI = [(7.8; 27.9)) GPs to 50 (89.3%; CI = (81.2; 97.4)) GPs (P < 0.001). In this study, GPs identified benign PSL most accurately after the 2nd session. This suggested that teaching GPs the basics of PSL would especially improve their diagnostic accuracy for benign PSL, which could reduce unnecessary referrals to dermatologists. Teaching basic knowledge of PSL in addition to melanoma recognition seemed to enable GPs to triage skin lesions more effectively than when they were only trained to recognize melanoma.

Characterization and risk factors of hyperglycaemia during treatment of childhood hematologic malignancies.

BACKGROUND: Secondary forms of diabetes are often understudied and underdiagnosed in children and adolescents with cancer. The objectives of our cohort study were to study the incidence and risk factors for hyperglycaemia in leukaemia and lymphoma patients. METHODS: We retrospectively collected 15 years of data from paediatric patients treated for acute lymphoblastic leukaemia (ALL), Hodgkin's lymphoma (HL), and non-Hodgkin's lymphoma (NHL) immediately at cancer diagnosis. We studied risk factors for hyperglycaemia in univariate and multivariate analyses. RESULTS: Our study cohort included 267 patients corresponding to 179 patients with ALL, 48 with NHL and 40 with HL. Eighteen per cent of ALL patients (32/179) and 17% of NHL patients (8/48) developed hyperglycaemia, with more than 61% developing hyperglycaemia within the first month of treatment. No hyperglycaemia was observed in HL patients. Multivariate analysis showed the following hyperglycaemia risk factors for ALL patients: overweight or obesity (OR 3.793) and pubertal onset (OR 4.269) at cancer diagnosis, steroid-resistant disease (OR 3.445) and hematopoietic stem cell transplant (HSCT) (OR 4.754). CONCLUSION: In our cohort, 18% of patients with ALL or NHL developed early-onset hyperglycaemia after chemotherapy/radiotherapy. Patients with ALL with increased hyperglycaemia risk can be readily identified by measuring BMI and puberty stage at cancer diagnosis. Also, glucose monitoring should be reinforced when patients show steroid-resistant disease and/or require HSCT.

Short- and Long-Term Evaluation of General Practitioners' Competences After a Training in Melanoma Diagnosis: Refresher Training Sessions May Be Needed.

General practitioners (GPs) are first-line clinicians in melanoma diagnosis. It is, therefore, important to ensure that they maintain their melanoma diagnostic accuracy over time. The objective of this study was to assess the short- and long-term competences of GPs after a training session in naked-eye melanoma diagnosis. An interventional prospective study was conducted whereby, over a 6-month period, GPs attended a 1-h melanoma diagnostic training session. To assess their acquired competences, GPs were asked to fill in a questionnaire on basic melanoma knowledge and to evaluate 10 clinical images of pigmented skin lesions prior to training, immediately after and 1 year later. In total, 89 GPs completed the questionnaire prior and immediately after training. As expected, the number of GPs who appropriately managed [Formula: see text] 50% of the melanoma cases increased after training (P < 0.001). One year after training, only 27 (30%) of the 89 GPs completed the questionnaire. This number of participants was too low to obtain significant figures but the GPs' mean overall score of appropriately managed clinical cases was much lower than in the immediate post-test. In conclusion, although this short training improved the GPs' diagnostic accuracy and management of melanoma in the short-term, participating GPs do not seem to have maintained these competences in the long-term. Further studies are needed to assess whether refresher training sessions are able to sustain acquired diagnostic and management skills.

Accurate non-tumoral 99mTc-MAA absorbed dose prediction to plan optimized activities in liver radioembolization using resin microspheres.

AIM: The manufacturers' recommended methods to calculate delivered activities in liver radioembolization are simplistic and only slightly personalized. Activity planning could also be based on a 99mTc-macroaggregated albumin SPECT/CT (MAA) using the partition model but its accuracy is controversial. This study evaluates the dose parameters in the normal liver and in the tumor compartments using MAA SPECT/CT (pre-therapeutic imaging) and 90Y TOF-PET/CT (post-therapy imaging). Finally, we propose a prescription of the activity as a function of the normal liver MAA distribution. METHOD: 66 procedures of RE (with resin microspheres) corresponding to 171 lesions were analyzed. Tumor to normal targeted liver uptake (T/NTL), tumor absorbed dose (TD) and whole normal liver absorbed (WNLD) were assessed with MAA and 90Y imaging. Secondly, activities were recalculated using the MAA distribution in the normal liver compartment to reach the maximal tolerable liver dose. These Activities were compared to activities defined with the BSA method. RESULTS: Compared to 90Y imaging, our study demonstrated an accurate estimation of the WNLD using MAA imaging (Pearson's R = 0.97, p < 0.001). On the contrary, significant variations were found for TD (R = 0.65, p < 0.001). The MAA T/NTL ratio has a 85% positive predictive value in identifying patients who will get a 90Y T/NTL ratio above 1.5. Moreover, activities calculated using the MAA distribution in the normal liver compartment were significantly higher to activities defined with the BSA method. CONCLUSION: Whole normal liver absorbed doses are accurately predicted with MAA imaging and could be used to optimize the activity planning.

Interaction between the Kansas City Cardiomyopathy Questionnaire and the Pocock's clinical score in predicting heart failure outcomes.

PURPOSE: Heart failure (HF) is a complex syndrome. Its appropriate management should combine several health measurements. We assessed the relationship between the Kansas City Cardiomyopathy Questionnaire (KCCQ) and the Pocock's clinical score. METHODS: We conducted a prospective registry of HF outpatients. The main outcome was occurrence of death or hospitalization during a 6-month follow-up. A multivariate logistic regression was performed, including the KCCQ overall summary score, the Pocock's clinical score and their interaction in the model. RESULTS: From January 2008 to December 2010, 143 patients were involved. Mean age of patients was 68 years, and 74% were men. KCCQ's overall summary score and Pocock's clinical score were inversely correlated (r = -0.24, p = 0.026). A total of 61 (42.7%) events occurred. There was a high proportion of events (77.8%) in patients with a Pocock's clinical score > 50%, whatever the KCCQ score value. When the KCCQ score was ≤ 50 %, there was a low increase in risk as the Pocock's clinical score increased (OR 2.0 [0.6; 6.6]). However, when the KCCQ score was between 50 and 75 or ≥ 75 %, there was a high increase in risk as the Pocock's clinical score increased (OR 6.9 [1.2; 38.9] and OR 7.4 [0.8; 69.7], respectively). CONCLUSIONS: Patients with a high Pocock's clinical score are at a high risk of death or hospitalization. For patients with a low Pocock's clinical score, the KCCQ score can identify those at risk of these events.