Correction: Effect of body tissue composition on the outcome of patients with metastatic non-small cell lung cancer treated with PD-1/PD-L1 inhibitors.

[This corrects the article DOI: 10.1371/journal.pone.0277708.].

Assessment of Diet Quality in Children and Adolescents with Overweight or Obesity in Greece.

The adoption of healthy nutritional habits constitutes one of the most important determinants of healthy growth and development in childhood. Few studies in Greece have examined children's diet quality using diet indices. The present study aimed to assess the diet quality of a large cohort of children and adolescents with overweight or obesity. Study participants (n = 1335), aged 2-18, were recruited through the Out-patient Clinic for the Prevention and Management of Overweight and Obesity in Childhood and Adolescence, Aghia Sophia Children's Hospital, Athens, Greece. Anthropometric, socio-demographic, and behavioral data were collected using standard methods and equipment. The Diet Quality Index (DQI), which includes four subcomponents (i.e., dietary diversity, dietary quality, dietary equilibrium, and meal index), was calculated to assess each subject's diet quality. According to the results of this study, children's total DQI score was 63.1%. It was observed that 66.7% of the children had at least moderate diet quality (total DQI ≥ 59.34%). Boys had higher values of the total DQI and certain components of the DQI (i.e., dietary equilibrium score and meal index) compared to girls. Three out of ten children with overweight/obesity had poor diet quality (i.e., DQI ≤ 59.33). Younger children (2-5 years old) were found to have the lowest values of dietary equilibrium compared to older children (6-9 and 12-18 years old). Moreover, boys had higher values of the total DQI score and of specific components of this index (i.e., dietary equilibrium and meal index) compared to girls. Children living in urban areas had higher values in the dietary quality score compared to those living in rural areas. Children with overweight had higher values of the dietary quality score and the total DQI score compared to children with obesity. The present study highlighted that children and adolescents with overweight or obesity have poor diet quality. Multilevel and higher intensity interventions should be designed specifically for this group to achieve tangible outcomes.

Effect of body tissue composition on the outcome of patients with metastatic non-small cell lung cancer treated with PD-1/PD-L1 inhibitors.

Obesity and sarcopenia have been reported to affect outcomes in patients with non-small cell lung cancer (NSCLC) treated with immune checkpoint inhibitors (ICIs). We analyzed prospective data from 52 patients with non-oncogene driven metastatic NSCLC treated with ICIs. Body tissue composition was calculated by measuring the fat and muscle densities at the level of 3rd lumbar vertebra in each patient computed tomography scan before ICI initiation using sliceOmatic tomovision. We converted the densities to indices [Intramuscular Fat Index (IMFI), Visceral Fat Index (VFI), Subcutaneous Fat Index (SFI), Lumbar Skeletal Muscle Index (LSMI)] by dividing them by height in meters squared. Patients were dichotomized based on their baseline IMFI, VFI and SFI according to their gender-specific median value. The cut-offs that were set for LMSI values were 55 cm2/m2 for males and 39 cm2/m2 for females. SFI distribution was significantly higher (p = 0.040) in responders compared to non-responders. None of the other variables affected response rates. Low LSMI HR: 2.90 (95% CI: 1.261-6.667, p = 0.012) and low SFI: 2.20 (95% CI: 1.114-4.333, p = 0.023) values predicted for inferior OS. VFI and IMFI values did not affect survival. Subcutaneous adipose and skeletal muscle tissue composition significantly affected immunotherapy outcomes in our cohort.

Do Children and Adolescents with Overweight or Obesity Adhere to the National Food-Based Dietary Guidelines in Greece?

Childhood obesity increases the risk for metabolic disorders, but is also related to nutritional deficiencies, such as anemia and hypovitaminosis D. Although children/adolescents with overweight/obesity may have higher energy intake, their diet quality and diversity may be low. The present study aimed to evaluate the consumption of foods against the national food-based dietary guidelines in children and adolescents with overweight or obesity in Greece. Sociodemographic, anthropometric and lifestyle data were collected from a sample of 1467 children 2-18 years old (962 obese, 505 overweight, 51.2% females) in 2014-2017. The results of this study show that the consumption of dairy products, fruit, vegetables, legumes and fish by children/adolescents with overweight or obesity was lower than the national recommendations (ranging from a minimum of 39.5% for fish, to a maximum of 75.5% for cereal/potato/rice). Only the consumption of meat/poultry was found to exceed the national recommendation (estimated coverage of 131.3%). Moreover, a large proportion of participants regularly consumed various unhealthy foods/beverages. The present findings indicate that the majority of children/adolescents with overweight/obesity do not comply with the national food-based dietary guidelines in Greece. The implementation of new strategies to promote healthy diets among children/adolescents with overweight/obesity are urgently required.

Cancer cachexia syndrome and clinical outcome in patients with metastatic non-small cell lung cancer treated with PD-1/PD-L1 inhibitors: results from a prospective, observational study.

BACKGROUND: Cancer cachexia syndrome (CCS) is an adverse prognostic factor in cancer patients undergoing chemotherapy or surgical procedures. We performed a prospective study to investigate the effect of CCS on treatment outcomes in patients with non-oncogene driven metastatic non-small cell lung cancer (NSCLC) undergoing therapy with programmed cell death protein 1 (PD-1)/programmed death ligand 1 (PD-L1) inhibitors. METHODS: Patients were categorized as having cancer cachexia if they had weight loss >5% in the last 6 months prior to immunotherapy (I-O) initiation or any degree of weight loss >2% and body mass index (BMI) <20 kg/m2 or skeletal muscle index at the level of third lumbar vertebra (LSMI) <55 cm2/m2 for males and <39 cm2/m2 for females. LSMI was calculated using computed tomography (CT) scans of the abdomen at the beginning of I-O and every 3 months thereafter. RESULTS: Eighty-three patients were included in the analysis and the prevalence of cancer cachexia at the beginning of I-O was 51.8%. The presence of CCS was associated with inferior response rates to ICIs (P≤0.001) and consisted an independent predictor of increased probability for developing disease progression as best response to treatment, OR =8.11 (95% CI: 2.95-22.40, P≤0.001). In the multivariate analysis, the presence of baseline cancer cachexia consisted an independent predictor for inferior survival, HR =2.52 (95% CI: 1.40-2.55, P=0.002). Reduction of LSMI >5% during treatment did not affect overall survival (OS; P=0.40). CONCLUSIONS: CCS is associated with reduced PD-1/PD-L1 inhibitor efficacy in NSCLC patients and should constitute an additional stratification factor in future I-O clinical trials. Further research at a translational and molecular level is required to decipher the mechanisms of interrelation of metabolic deregulation and suppression of antitumor immunity.

Myostatin in combination with creatine phosphokinase or albumin may differentiate patients with cirrhosis and sarcopenia.

In patients with liver cirrhosis (LC), sarcopenia is correlated with frequent complications and increased mortality. Myostatin, a myokine, is a potential biomarker of skeletal mass and/or sarcopenia. The aim of this study was to examine the association between myostatin and muscle mass and evaluate myostatin as a biomarker of sarcopenia in LC. Skeletal muscle index (SMI) and myosteatosis were evaluated by computed tomography scan. Muscle quantity and quality along with muscle strength and function were used to diagnose sarcopenia. Serum myostatin was measured by ELISA. One hundred and fifteen consecutive patients with LC [72.2% male, median age 59 yr (IQR 52-67), MELD 12 (8-16), 28.7% with compensated LC] were included. Low SMI was diagnosed in 49.6% and sarcopenia in 34.8% (21.7% severe). Myostatin levels were lower in low (P < 0.001) compared with patients with normal SMI and were strongly correlated with SMI in MELD score ≥ 15 (r = 0.571, P < 0.001). Myostatin was also lower in patients with sarcopenia compared with those without (P < 0.001) and even lower in severe sarcopenia (P < 0.001). In multivariate analysis, myostatin, age, and albumin remained significant predictors of low SMI after adjustment for sex, MELD, and creatine phosphokinase (CPK). Similarly, myostatin and age predicted sarcopenia after adjustment for sex, MELD, CPK, and albumin. The ratios log10myostatin-to-CPK or albumin-to-myostatin were found to have acceptable diagnostic accuracy in ruling out sarcopenia in total patients. However, the best diagnostic performance was shown in MELD ≥ 15 (AUROC 0.829 or 0.801, respectively). Myostatin is independently associated with both skeletal muscle mass and sarcopenia. Myostatin in combination with CPK or albumin are good surrogate markers in excluding sarcopenia.NEW & NOTEWORTHY Serum levels of myostatin were significantly lower in cirrhotic patients with impaired skeletal mass index (SMI) and sarcopenia than those without. Serum levels of myostatin have a positive correlation with SMI. Myostatin levels are independently associated with sarcopenia, diagnosed according to the latest criteria, in patients with cirrhosis. Myostatin in combination with creatine phosphokinase or albumin have good accuracy excluding sarcopenia in patients with cirrhosis.

Assessment of dietary habits and the adequacy of dietary intake of patients with cirrhosis-the KIRRHOS study.

BACKGROUND & AIMS: Undernutrition is widely prevalent in patients with cirrhosis and affects prognosis. Given the lack of data regarding the dietary intake (DI) and habits of patients with cirrhosis, the aim of the present study was to evaluate them by assessing diet's adequacy compared to the new guidelines, and the association of DI with nutritional status indicators. METHODS: One hundred and eighty-seven patients (57.8% male, 59.9 ± 10.9 years old, 44.9% decompensated ones) with cirrhosis of various etiologies were enrolled. The patients' DI was assessed using three 24 h recalls, which were analyzed regarding macronutrients' intake, food groups consumption, adherence to the Mediterranean diet and meal patterns. The Goldberg cut-off limits for the ratio of energy intake to resting energy expenditure were used to evaluate dietary underreporting and patients were accordingly classified as low or adequate energy reporters (LERs and AERs). RESULTS: Among the AERs (n = 91, 48.7%) only 29.7% and 31.9% met current recommendations regarding energy and protein intake, accordingly. Patients reported low intake of several healthy food groups and low adherence to the Mediterranean diet. They reported a median of 4.3 eating episodes per day and they frequently omitted late evening snack. Nevertheless, no statistically significant associations were found between parameters of DI and annual and two-year survival. CONCLUSIONS: Low energy reporting was very frequent in this sample of patients with liver cirrhosis. Diet quality was rather poor, whereas energy and protein intakes were lower than those recommended.

A Comprehensive Multidisciplinary Management Plan Is Effective in Reducing the Prevalence of Overweight and Obesity in Childhood and Adolescence.

BACKGROUND: Obesity in childhood and adolescence represents a major health problem of our century. In Greece, 30-35% of children and adolescents are overweight or obese. Objective and Hypotheses: To investigate the effectiveness of a comprehensive multidisciplinary personalized management plan at reducing the prevalence of overweight and obesity in childhood and adolescence. PATIENTS AND METHODS: One thousand (n = 1,000) children and adolescents aged 2-18 years (mean age ± SD: 10.09 ± 2.86 years; 520 females, 480 males) were studied prospectively. Subjects were classified as obese (n = 579, 57.9%), overweight (n = 295, 29.5%) or having a normal body mass index (BMI) (n = 126, 12.6%) according to the International Obesity Task Force cutoff points. All subjects were evaluated by a multidisciplinary team at frequent intervals, received personalized advice on diet and exercise and were studied prospectively for 1 year. Detailed clinical evaluation and laboratory investigations were performed at the beginning and at the end of the study. RESULTS: At initial evaluation, 57.9% of subjects were obese, 29.5% overweight and 12.6% of normal BMI. Indices of cardiometabolic disease were higher in obese than in overweight and normal-BMI subjects. Following 1 year of multidisciplinary management interventions, the prevalence of obesity decreased by 16.8%, the prevalence of normal BMI increased by 8.2%, and all cardiometabolic indices improved significantly. CONCLUSIONS: A personalized multidisciplinary management plan is effective at reducing the prevalence of obesity in childhood and adolescence.

Validation of cutoffs for skeletal muscle mass index based on computed tomography analysis against dual energy X-ray absorptiometry in patients with cirrhosis: the KIRRHOS study.

BACKGROUND: Accurate assessments of muscle mass in patients with cirrhosis are necessary in clinical practice. Computed tomography (CT) of the upper abdomen has been proposed as a useful method for quantifying muscle mass. Recently, Carey et al developed specific cutoffs for muscle wasting based on the skeletal muscle index at the L3 vertebra (L3-SMI) for cirrhotic patients. The aim of the present study was to assess the concurrent validity of the newly proposed cutoffs of Carey et al, along with others widely used in several clinical contexts, using dual energy X-ray absorptiometry (DXA) as the reference method. METHODS: Data were evaluated from 97 Caucasian patients (59.8% male, 59.1±11.6 years old, 45.4% decompensated) with cirrhosis of various etiologies. Muscle mass was assessed using the appendicular lean mass index (ALMI) by DXA and the L3-SMI by CT. Low L3-SMI was defined in relation to 5 different cutoffs. RESULTS: Low muscle mass prevalence was 13.4% according to ALMI and 26.8-45.4% according to the different cutoffs applied for L3-SMI. The Carey et al, Prado et al and Montano-Loza et al cutoffs showed similar sensitivity (all 69.2%) and specificity (79.8%, 76.2% and 75.0%, respectively) and high accuracy (78.4%, 75.3% and 74.2%). The Carey et al cutoffs showed the highest diagnostic validity against DXA the multivariate odds ratio adjusted for age, sex, body mass index category, disease etiology and model for end-stage liver disease score (95% confidence interval) was 5.88 (1.36-25.4), P=0.018. CONCLUSION: Compared to DXA, the cutoffs for identifying muscle wasting proposed by Carey et al were proven to be the most accurate.

Evaluation of the effectiveness of eight screening tools in detecting risk of malnutrition in cirrhotic patients: the KIRRHOS study.

Malnutrition risk screening in cirrhotic patients is crucial, as poor nutritional status negatively affects disease prognosis and survival. Given that a variety of malnutrition screening tools is usually used in routine clinical practice, the effectiveness of eight screening tools in detecting malnutrition risk in cirrhotic patients was sought. A total of 170 patients (57·1 % male, 59·4 (sd 10·5) years, 50·6 % decompensated ones) with cirrhosis of various aetiologies were enrolled. Nutritional screening was performed using the Malnutrition Universal Screening Tool, Nutritional Risk Index, Malnutrition Screening Tool, Nutritional Risk Screening (NRS-2002), Birmingham Nutritional Risk Score, Short Nutritional Assessment Questionnaire, Royal Free Hospital Nutritional Prioritizing Tool (RFH-NPT) and Liver Disease Undernutrition Screening Tool (LDUST). Malnutrition diagnosis was defined using the Subjective Global Assessment (SGA). Data on 1-year survival were available for 145 patients. The prevalence of malnutrition risk varied according to the screening tools used, with a range of 13·5-54·1 %. RFH-NPT and LDUST were the most accurate in detecting malnutrition (AUC = 0·885 and 0·892, respectively) with a high sensitivity (97·4 and 94·9 %, respectively) and fair specificity (73·3 and 58 %, respectively). Malnutrition according to SGA was an independent prognostic factor of within 1-year mortality (relative risk was 2·17 (95 % CI 1·0, 4·7), P = 0·049) after adjustment for sex, age, disease aetiology and Model for End-stage Liver Disease score, whereas nutrition risk according to RFH-NPT, LDUST and NRS-2002 showed no association. RFH-NPT and LDUST were the only screening tools that proved to be accurate in detecting malnutrition in cirrhotic patients.

An interlaboratory transfer of a multi-analyte assay between continents.

Alex has worked at GlaxoSmithKline for the past 15 years and currently works within the bioanalytical and toxicokinetic group in the United Kingdom. Alex's role in previous years has been the in-house support of preclinical and clinical bioanalysis, from method development through to sample analysis activities as well as acting as PI for GLP bioanalysis and toxicokinetics. For the past two years, Alex has applied this analytical and regulatory experience to focus on the outsourcing of preclinical bioanalysis, toxicokinetics and clinical bioanalysis, working closely with multiple bioanalytical and in-life CRO partners worldwide. Alex works to support DMPK and Safety Assessment outsourcing activities for GSK across multiple therapeutic areas, from the first GLP study through to late stage clinical PK studies. Transfer and cross-validation of an existing analytical assay between a laboratory providing current analytical support, and a laboratory needed for new or additional support, can present the bioanalyst with numerous challenges. These challenges can be technical or logistical in nature and may prove to be significant when transferring an assay between laboratories in different continents. Part of GlaxoSmithKline's strategy to improve confidence in providing quality data, is to cross-validate between laboratories. If the cross-validation fails predefined acceptance criteria, then a subsequent investigation would follow. This may also prove to be challenging. The importance of thorough planning and good communication throughout assay transfer, cross-validation and any subsequent investigations is illustrated in this case study.

Conceptual framework of a simplified multi-dimensional model presenting the environmental and personal determinants of cardiometabolic risk behaviors in childhood.

Clinical manifestations of cardiometabolic risk (CMR) may be set early in childhood due to unfavorable behaviors or lifestyle patterns related to diet and physical activity. Several factors may determine the adoption of such lifestyle-related behaviors, which researchers have tried to cluster under certain frameworks or models. In this context, the framework developed and proposed by this review gathers all the present knowledge regarding these determining factors to date and groups them into three main categories related to personal characteristics and the social and physical environment. Based on the proposed framework, a large variety of personal, social and physical environmental factors can positively or negatively influence CMR-related behaviors (either directly or indirectly via their interrelations), thus leading to decreased or increased risk, respectively. This framework could be of great value to public health policy makers and legislators for designing and implementing interventional programs tailored to the needs of susceptible population groups who are most in need for such initiatives. Targeting the correlates as potential determinants of CMR-related behaviors, and not just on the behaviors themselves, has been shown previously to be the most effective approach for tackling health issues related to CMR starting from early life stages.

Association of distorted eating behaviors with cardiometabolic risk indices in preadolescents. The Healthy Growth Study.

The association between distorted eating behavior (DEB) with cardiometabolic risk (CMR) in children has been poorly investigated. The aim of the study was to examine the association between DEB with certain CMR indices in 9- to 13-year-old children in Greece. A cross-sectional epidemiological study was conducted among 1803 schoolchildren from 77 primary schools in 4 counties of Greece with full data on DEBQ and ChEAT questionnaires and CMR indices. Children underwent anthropometric measurements and Tanner stage, serum lipid, glucose, insulin and HOMA-IR levels assessments. Univariate and multivariate linear regression analyses were performed to test for the association between components of DEBQ and ChEAT with CMR indices. Several significant associations between components of DEBQ and ChEAT with CMR indices were observed when tested at univariate regression models in both boys and girls. However, after adjusting for several possible confounders, including Tanner stage, all significant associations were lost in girls while only a few remained in boys. Thus, DEB might have an unfavorable effect also in certain CMR indices, besides nourishment status. This is more pronounced in preadolescent boys for whom hormonal changes due to the transition to adolescence have not yet been established compared to girls. Still further research is needed to shed more light on these associations.