Determinants of weight, psychological status, food contemplation and lifestyle changes in patients with obesity during the COVID-19 lockdown: a nationwide survey using multiple correspondence analysis.

INTRODUCTION: The corona virus disease 2019 (COVID-19) pandemic forced most of the Italian population into lockdown from 11 March to 18 May 2020. A nationwide survey of Italian Clinical Nutrition and Dietetic Services (Obesity Centers or OCs) was carried out to assess the impact of lockdown restrictions on the physical and mental wellbeing of patients with obesity (PWO) who had follow-up appointments postponed due to lockdown restrictions and to compare determinants of weight gain before and after the pandemic. METHODS: We designed a structured 77-item questionnaire covering employment status, diet, physical activity and psychological aspects, that was disseminated through follow-up calls and online between 2 May and 25 June 2020. Data were analyzed by multiple correspondence analysis (MCA) and multiple linear regression. RESULTS: A total of 1,232 PWO from 26 OCs completed the questionnaires (72% female, mean age 50.2 ± 14.2 years; mean BMI 34.7 ± 7.6 kg/m2; 41% obesity class II to III). During the lockdown, 48.8% gained, 27.1% lost, while the remainder (24.1%) maintained their weight. The mean weight change was +2.3 ± 4.8 kg (in weight gainers: +4.0 ± 2.4 kg; +4.2% ± 5.4%). Approximately 37% of participants experienced increased emotional difficulties, mostly fear and dissatisfaction. Sixty-one percent reduced their physical activity (PA) and 55% experienced a change in sleep quality/quantity. The lack of online contact (37.5%) with the OC during lockdown strongly correlated with weight gain (p < 0.001). Using MCA, two main clusters were identified: those with unchanged or even improved lifestyles during lockdown (Cluster 1) and those with worse lifestyles during the same time (Cluster 2). The latter includes unemployed people experiencing depression, boredom, dissatisfaction and increased food contemplation and weight gain. Within Cluster 2, homemakers reported gaining weight and experiencing anger due to home confinement. CONCLUSIONS: Among Italian PWO, work status, emotional dysregulation, and lack of online communication with OCs were determinants of weight gain during the lockdown period.

Weight loss and clinical characteristics of young adults patients seeking treatment at medical centers: data from the QUOVADIS Study.

OBJECTIVE: To compare clinical characteristics, attrition, weight loss, and psychological changes of obese young adults and obese adults seeking treatment. MATERIALS AND METHODS: 1530 individuals seeking treatment in 18 Italian medical centers were evaluated. 382 cases (25%) were classified as young adults (age≤35 years), 1148 (75%) as adults (>35 years). Psychological distress, binge eating, body uneasiness, and attitude towards eating were evaluated, at baseline and after a 12-month weight-loss program, together with BMI changes. Weight-loss expectations and primary motivation for seeking treatment were also recorded. RESULTS: At baseline, young adults reported significantly higher BMI at age 20, weight loss expectations and body uneasiness scores than adults. A significantly higher percentage of young adults also reported improving appearance as primary reason for seeking treatment. The attrition rate was significantly larger in young adults. Among completers, the mean percent weight loss at 12 months and improvement of psychosocial variables were significantly higher in young adults than in adults. By intention to treat, BMI changes were no longer significant between groups. DISCUSSION: Obese young adults lose more weight and considerably improve psychological distress, but show a higher attrition rate after 12 months of continuous care in a real world medical setting.

[Obesity and Eating Disorders. Indications for the different levels of care. An Italian Expert Consensus Document]. / Documento di Consensus. Obesità e Disturbi dell'Alimentazione Indicazioni per i diversi livelli di trattamento.

This paper is an Italian Expert Consensus Document on multidimensional treatment of obesity and eating disorders. The Document is based on a wide survey of expert opinion. It presents, in particular, considerations regarding how clinicians go about choosing the most appropriate site of treatment for a given patient suffering from obesity and/or eating disorders: outpatient, partial hospitalization, residential rehabilitation centre, inpatient hospitalization. In a majority of instances obesity and eating disorders are long-term diseases and require a multiprofessional team-approach. In determining an initial level of care or a change to a different level of care, it is essential to consider together the overall physical condition, medical complications, disabilities, psychiatric comorbidity, psychology, behaviour, family, social resources, environment, and available services. We first created a review manuscript, a skeleton algorithm and two rating scales, based on the published guidelines and the existing research literature. As the second point we highlighted a number of clinical questions that had to be addressed in the specific context of our National Health Service and available specialized care units. Then we submitted eleven progressive revisions of the Document to the experts up to the final synthesis that was approved by the group. Of course, from point to point, some of the individual experts would differ with the consensus view. The document can be viewed as an expert consultation and the clinical judgement must always be tailored to the particular needs of each clinical situation. We will continue to revise the Document periodically based on new research information and on reassessment of expert opinion to keep it up-to-date. The Document was not financially sponsored.

Effects of an Intensive Inpatient Rehabilitation Program in Elderly Patients with Obesity.

OBJECTIVE: The aim of this study was to assess the short-term effectiveness of an intensive inpatient multidimensional rehabilitation program (MRP), including diet, exercise, and behavioral therapy, in elderly patients with severe obesity. METHODS: Forty-four elderly patients (old; age 69.3 ± 3.5 years, BMI 41.9 ± 14.9) were analyzed against 215 younger patients (young; age 48.2 ± 18.5 years, BMI 43.9 ± 9.4), who were used as controls. All patients underwent MRP, based on group therapy guided by a multidisciplinary team (physicians, dietitians, exercise trainers, psychologists). We evaluated changes in anthropometry, cardiovascular risk factors, physical fitness, quality of life, and eating behavior. RESULTS: After 3 weeks of MRP, we observed a reduction in body weight (old -3.8%, young -4.3%), BMI (old -3.9%, young -4.4%), waist circumference (old -3.4%, young -4.1%), total cholesterol (old -14.0%, young -15.0%), and fasting glucose (old -8.3%, young -8.1%), as well as improved performance in the Six-Minute-Walk Test (old +28.7%, young +15.3%), chair-stand test (old +24.8%, young +26.9%), and arm-curl test (old +15.2%, young +27.3%). Significant improvement was registered in all other analyzed domains. CONCLUSION: Our 3-week MRP provided significant clinical and functional improvement, which was similar between elderly and younger patients with severe obesity. In the long-term, this may be translated into better quality of life, through better management of obesity-associated morbidities and reduced frailty.

PARP inhibitors enhance replication stress and cause mitotic catastrophe in MYCN-dependent neuroblastoma.

High-risk and MYCN-amplified neuroblastomas are among the most aggressive pediatric tumors. Despite intense multimodality therapies, about 50% of these patients succumb to their disease, making the search for effective therapies an absolute priority. Due to the important functions of poly (ADP-ribose) polymerases, PARP inhibitors have entered the clinical settings for cancer treatment and are being exploited in a variety of preclinical studies and clinical trials. PARP inhibitors based combination schemes have also been tested in neuroblastoma preclinical models with encouraging results. However, the expression of PARP enzymes in human neuroblastoma and the biological consequences of their inhibition remained largely unexplored. Here, we show that high PARP1 and PARP2 expression is significantly associated with high-risk neuroblastoma cases and poor survival, highlighting its previously unrecognized prognostic value for human neuroblastoma. In vitro, PARP1 and 2 are abundant in MYCN amplified and MYCN-overexpressing cells. In this context, PARP inhibitors with high 'PARP trapping' potency, such as olaparib or talazoparib, yield DNA damage and cell death preceded by intense signs of replication stress. Notwithstanding the activation of a CHK1-CDC25A replication stress response, PARP-inhibited MYCN amplified and overexpressing cells fail to sustain a prolonged checkpoint and progress through mitosis in the presence of damaged DNA, eventually undergoing mitotic catastrophe. CHK1-targeted inhibition of the replication stress checkpoint exacerbated this phenotype. These data highlight a novel route for cell death induction by PARP inhibitors and support their introduction, together with CHK1 inhibitors, in therapeutic approaches for neuroblastomas with high MYC(N) activity.

Circulating ghrelin level is increased in coeliac disease as in functional dyspepsia and reverts to normal during gluten-free diet.

BACKGROUND: It is controversial whether serum ghrelin concentration is altered in coeliac disease and whether this alteration is related to nutritional impairment or to inflammatory changes of duodenal mucosa. AIM: To investigate clinical and histopathological variables affecting circulating ghrelin in coeliac patients by comparison with dyspeptic patients and with healthy controls. METHODS: We measured serum ghrelin and obtained gastric and duodenal biopsies in 44 coeliac patients before and after 1-year gluten-free diet, in 39 dyspeptic patients and 53 healthy controls. RESULTS: Serum ghrelin concentration was significantly higher in coeliac (531 +/- 29 pg/mL, P < 0.05) and in dyspeptic patients (526 +/- 14 pg/mL, P < 0.01) than in healthy controls (451 +/- 8 pg/mL), and body mass index was significantly lower in coeliac (20 +/- 1) and in dyspeptic patients (20 +/- 1) than in healthy controls (22 +/- 1, P < 0.05). In coeliac patients serum ghrelin concentration was not related to the severity of duodenal lesions. Serum ghrelin reverted to normal (399 +/- 30 pg/mL) and body mass index increased significantly (0.6 +/- 0.1 kg/m(2) increase, P < 0.05) during gluten-free diet despite persistent duodenal lymphocytic infiltration. CONCLUSIONS: Ghrelin concentration is increased and body mass index is decreased in coeliac and in dyspeptic patients irrespective of presence and severity of duodenal inflammation. Nutritional impairment is a key factor in elevating plasma ghrelin levels in coeliac disease.

The MRN complex is transcriptionally regulated by MYCN during neural cell proliferation to control replication stress.

The MRE11/RAD50/NBS1 (MRN) complex is a major sensor of DNA double strand breaks, whose role in controlling faithful DNA replication and preventing replication stress is also emerging. Inactivation of the MRN complex invariably leads to developmental and/or degenerative neuronal defects, the pathogenesis of which still remains poorly understood. In particular, NBS1 gene mutations are associated with microcephaly and strongly impaired cerebellar development, both in humans and in the mouse model. These phenotypes strikingly overlap those induced by inactivation of MYCN, an essential promoter of the expansion of neuronal stem and progenitor cells, suggesting that MYCN and the MRN complex might be connected on a unique pathway essential for the safe expansion of neuronal cells. Here, we show that MYCN transcriptionally controls the expression of each component of the MRN complex. By genetic and pharmacological inhibition of the MRN complex in a MYCN overexpression model and in the more physiological context of the Hedgehog-dependent expansion of primary cerebellar granule progenitor cells, we also show that the MRN complex is required for MYCN-dependent proliferation. Indeed, its inhibition resulted in DNA damage, activation of a DNA damage response, and cell death in a MYCN- and replication-dependent manner. Our data indicate the MRN complex is essential to restrain MYCN-induced replication stress during neural cell proliferation and support the hypothesis that replication-born DNA damage is responsible for the neuronal defects associated with MRN dysfunctions.

Personality, attrition and weight loss in treatment seeking women with obesity.

Studies on small samples or in single units applying specific treatment programmes found an association between some personality traits and attrition and weight loss in individuals treated for obesity. We aimed to investigate whether pre-treatment personality traits were associated with weight loss outcomes in the general population of women with obesity. Attrition and weight loss outcomes after 12 months were measured in 634 women with obesity (mean age, 48; body mass index (BMI), 37.8 kg m(-2)) seeking treatment at eight Italian medical centres, applying different medical/cognitive behavioural programmes. Personality traits were assessed with the Temperament and Character Inventory (TCI), eating disorder features with the Binge Eating Scale (BES) and Night Eating Questionnaire (NEQ). Within the 12-month observation period, 32.3% of cases were lost to follow-up. After adjustment for demographic confounders and the severity of eating disorders, no TCI personality traits were significantly associated with attrition, while low scores of the novelty seeking temperament scale remained significantly associated with weight loss ≥ 10% (odds ratio, 0.983; 95% confidence interval, 0.975-0.992). Additional adjustment for education and job did not change the results. We conclude that personality does not systematically influence attrition in women with obesity enrolled into weight loss programmes in the community, whereas an association is maintained between novelty seeking and weight loss outcome. Studies adapting obesity interventions on the basis of individual novelty seeking scores might be warranted to maximize the results on body weight.

Review article: gall-bladder motor function in obesity.

A number of epidemiological studies has established obesity as a risk factor for gallstone disease. More recently, studies have suggested a relationship between gallstone disease and the metabolic syndrome linked to central adiposity, whose cardinal feature is represented by hyperinsulinaemia. Studies on fasting gall-bladder volume in obese subjects show that this parameter correlates with weight, body mass index (BMI) and body surface area; however, this is also true for large-sized non-obese subjects. Gall-bladder volume also correlates with abdominal fat and with impaired glucose tolerance. In contrast to the well-established role of bile supersaturation in the pathogenesis of gallstones in obesity, data are controversial on whether gall-bladder motor function is defective in obese subjects. However, studies were heterogeneous for subjects' BMI, emptying stimulus, technique used and parameters assessed to evaluate gall-bladder motor function. Also, differences in baseline gall-bladder volume may lead to wide differences in bile 'washout' effect despite apparently similar percentage changes in volume or content. Although post-prandial plasma levels of cholecystokinin (CCK) are normal in obese subjects, there is some evidence that a sub-group of obese subjects could have decreased sensitivity to CCK, possibly mediated by hyperinsulinaemia. Further studies using standard physiological stimuli and controlling for glucose tolerance, fasting insulin levels and baseline gall-bladder volume are needed to establish the role of gall-bladder motor function in the pathogenesis of gallstone disease in obesity.

Review: low caloric intake and gall-bladder motor function.

Cholelithiasis is the primary expression of obesity in the hepatobiliary system. In obese subjects the risk of developing gallstones is increased due to a higher cholesterol saturation of gall-bladder bile. During weight reduction with very low calorie diets (VLCD) the incidence of gallstones increases, but the mechanism for gallstone formation is not completely understood and several pathogenetic mechanisms have been suggested: increased saturation of bile, increased gall-bladder secretion of mucin and calcium, increased presence of prostaglandins and arachidonic acid. Alterations in gall-bladder motility may contribute to gallstone formation, but few studies have addressed the issue of gall-bladder motility during rapid weight loss and its possible role in gallstone formation. VLCD have been associated with a gall-bladder stasis, as a consequence of reduced gall-bladder stimulation by low fat content of the diets. A threshold quantity of fat (10 g) has been documented to obtain efficient gall-bladder emptying. Ursodeoxycholic acid administered during VLCD seems to have a protective role in developing a biliary cholesterol crystals. Gall-bladder emptying was lower in response to low fat meals with respect to relative higher fat meals, before as well as during the VLCD. This may account the possibility of an adaptative response of the gall-bladder motility to a given diet regimen. Adequate fat content of the VLCD may prevent gallstone formation, maintaining adequate gall-bladder motility and may be more economic and physiologically acceptable than administration of a pharmacological agent.

Ursodeoxycholic acid alone or with chenodeoxycholic acid for dissolution of cholesterol gallstones: a randomized multicentre trial. The British-Italian Gallstone Study group.

BACKGROUND: Combination therapy using ursodeoxycholic acid plus chenodeoxycholic acid has been advocated for dissolution of cholesterol gallstones because the two bile acids have complementary effects on biliary lipid metabolism and cholesterol solubilization. AIM: To compare the clinical efficacy of combination therapy with ursodeoxycholic acid monotherapy. PATIENTS AND METHODS: A total of 154 symptomatic patients with radiolucent stones (< or = 15 mm) in functioning gallbladders were enrolled from six centres in England and Italy. They were randomized to either a combination of chenodeoxycholic acid plus ursodeoxycholic acid (5 mg.day/kg each) or to ursodeoxycholic acid alone (10 mg.day/kg). Dissolution was assessed by 6-monthly oral cholecystography and ultrasonography for up to 24 months. RESULTS: Both regimens reduced the frequency of biliary pain and there was no significant difference between them in terms of side-effects or dropout rate. Complete gallstone dissolution on an intention-to-treat basis was similar at all time intervals. At 24 months this was 28% with ursodeoxycholic acid alone and 30% with combination therapy. The mean dissolution rates at 6 and 12 months were 47% and 59% with ursodeoxycholic acid, and 44% and 59% with combination therapy, respectively. CONCLUSION: There is no substantial difference in the efficacy of combined ursodeoxycholic acid and chenodeoxycholic acid and that of ursodeoxycholic acid alone in terms of gallstone dissolution rate, complete gallstone dissolution, or relief of biliary pain.

Haemophilus influenzae type b in respiratory secretions.

Oral and respiratory secretions of 31 children who were healthy or had mild upper respiratory infection, and who had a positive throat culture for Haemophilus influenzae type b, were cultured to determine which secretions contain this organism and how long it can be recovered from fomites. Rhinorrhea was present in 11 of 31 (34%) children and nasal mucus was positive for H. influenzae type b in 10 (91%). In 5 of these children the concentration of H. influenzae type b in nasal mucus was 10(4) to 10(7) colony-forming units/ml3. H. influenzae type b in nasal mucus applied to fomites were recovered for 12 hours. Cultures of saliva and cough secretions compared with nasal mucus were less often positive (3 of 31, P less than 0.001; 3 of 25, P less than 0.001, respectively) and contained fewer H. influenzae type b (5 and 15 colony-forming units, respectively). H. influenzae type b was recovered from the hand of 2 of 27 (7%) children; both children had positive cultures of saliva. These data indicate that H. influenzae type b can be found in oral and respiratory secretions of pharyngeal carriers and can contaminate children's hands. Nasal mucus was the most consistently positive secretion and contained the largest number of bacteria. Careful management of nasal mucus secretions is warranted in settings where transmission could occur to susceptible children.

Postprandial refilling and turnover: specific gallbladder motor function defects in patients with gallstone recurrence.

BACKGROUND AND AIMS: Impaired gallbladder motor functions are important in the pathogenesis of primary cholesterol gallstones, and possibly in the pathogenesis of recurrent gallstones. By using ultrasonography and cholescintigraphy simultaneously, we recently defined new parameters of gallbladder motor function (postprandial refilling and turnover in addition to emptying), which were markedly impaired in gallstone patients. The aim of this study was to assess the value of these new parameters in distinguishing patients with from those without gallstone recurrence. METHODS: We studied 11 patients with gallstone recurrence, 11 without gallstone recurrence (at least 40 months after complete dissolution by oral bile acids) and 11 healthy controls. Simultaneous measurements of gallbladder volume (ultrasound) and gallbladder counts (gamma-camera scintigraphy) were carried out in the fasting state and at 10 min intervals following meal ingestion, for a period of 90 min. Gallbladder refilling, turnover of bile and turnover index were calculated, as well as gallbladder emptying by both cholescintigraphy and ultrasound. RESULTS: Patients with gallstone recurrence had reductions in gallbladder emptying, postprandial refilling and gallbladder bile turnover. They also had a significant reduction in the turnover index (1.7 +/- 1.4) compared to controls (3.5 +/- 0.3, P < 0.01) and to patients without gallstone recurrence (3.1 +/- 1.5, P < 0.05). Patients without gallstone recurrence had only a small reduction in emptying and no reduction in postprandial refilling or turnover compared to controls. CONCLUSIONS: We conclude that impairment of gallbladder emptying persists in all patients after gallstone dissolution, albeit to a more pronounced extent in patients with recurrence; but that impairment of postprandial refilling and turnover are specific defects in patients with recurrence.

Risk factors for the development of gallstone recurrence following medical dissolution. The British-Italian Gallstone Study Group.

OBJECTIVE: To assess risk factors for gallstone recurrence following non-surgical treatment. DESIGN: A prospective follow-up of a multicentre cohort of post-dissolution gallstone patients. SETTING: Six gastroenterology units in the UK and Italy. PARTICIPANTS: One hundred and sixty-three patients with confirmed gallstone dissolution following non-surgical therapy (bile acids or lithotripsy plus bile acids), followed up by ultrasound scan and clinical assessment at 6-monthly intervals for up to 6 years (median, 25 months; range, 6-70 months). OUTCOME MEASURES: Subject-related variables (sex, age, height, weight, body mass index), gallstone-related variables (number, diameter, presence of symptoms, months to complete stone clearance), treatment modalities (bile acid therapy, extracorporeal shock wave lithotripsy) and follow-up related variables (weight change, use of non-steroidal anti-inflammatory agents, statins, pregnancies and/or use of oestrogens) were assessed by univariate and multivariate analysis as putative risk factors for gallstone recurrence. RESULTS: Forty-five gallstone recurrences were observed during the follow-up period. Multiple primary gallstones and length of time to achieve gallstone dissolution were the only variables associated with a significant increase in the recurrence rate. Appearance of biliary sludge during follow-up was also significantly related to development of gallstone recurrence. Use of statins or non-steroidal anti-inflammatory agents did not confer protection against recurrence. CONCLUSIONS: Patients with primary single stones are the best candidates for non-surgical treatment of gallstones, because of a low risk of gallstone recurrence. The positive association of recurrence with biliary sludge formation and time to dissolution of primary stones may provide indirect confirmation for the role of impaired gallbladder motility in the pathogenesis of this condition.

Feasibility of air plethysmography (BOD POD) in morbid obesity: a pilot study.

The assessment of body composition (BC) in morbidly obese patients is a difficult procedure. Air-displacement plethysmography (ADP), which measures body density, is a very promising technique for BC assessment in health and disease. However, there are very few data about the feasibility of applying ADP on morbidly obese patients, which theoretically could be affected by large body size and difficulty in lung volume measurements. The main aim of this pilot study was to evaluate the feasibility of using ADP for BC assessment in morbidly obese patients. We studied nine subjects (6 males and 3 females) who had a mean age (+/-SD) of 47.0+/-13.5 years and body mass index (BMI) of 46.6+/-7.7 kg/m(2) (range 36.4-58.8). All patients could fit into the instrument chamber and perform the manoeuvre for pulmonary plethysmography. Mean lung volume was 3.9+/-1.2 l and mean percent body fat was 53.1+/-6.6 (range 46.0-67.5). These results indicate that ADP appears to be suitable for patients with BMI over 40 kg/m(2) and produces realistic BC data.

Body composition in advanced-stage Parkinson's disease.

Little is known about body composition in Parkinson's disease (PD). We studied 35 patients (20 male, 15 female subjects; mean age 69.7+/-5.8 years) with advanced PD by anthropometry, dual-energy X-ray absorptiometry (DEXA), and serum 25-OH vitamin D measurement. Over 70% of patients had a disease duration of more than 4 years; all were on L-dopa treatment. Low levels of serum 25-OH vitamin D were present in 41% of the patients. The mean body mass index (BMI) was 25.3+/-4.3 kg/m(2) (range 17.1-37.3). Mid-arm muscle circumference was below the 10th percentile in 23%. For whole-body mean (+/-SD) bone mineral density, the T score was below -1 SD in 35% of patients, and the Z score was below -1 SD in 24%. Percent fat mass measured with DEXA was 30.6+/-11.4% (range 10.1-45.5) in the overall sample; it was 21.1+/-8.8% (range 10.1-30.4) in male subjects and 38.1+/-9.2% (range 25.8-45.5) in female subjects. We conclude that advanced-stage PD may show excess adiposity coexisting with depletion of lean body mass (sarcopenic obesity), in addition to decreased whole-body bone mineral density associated with low serum 25-OH vitamin D. A low level of physical activity and inadequate exposure to sunlight are likely to be among the putative causes.

Galectin-3 is a marker of favorable prognosis and a biologically relevant molecule in neuroblastic tumors.

Childhood neuroblastic tumors are characterized by heterogeneous clinical courses, ranging from benign ganglioneuroma (GN) to highly lethal neuroblastoma (NB). Although a refined prognostic evaluation and risk stratification of each tumor patient is becoming increasingly essential to personalize treatment options, currently only few biomolecular markers (essentially MYCN amplification, chromosome 11q status and DNA ploidy) are validated for this purpose in neuroblastic tumors. Here we report that Galectin-3 (Gal-3), a ß-galactoside-binding lectin involved in multiple biological functions that has already acquired diagnostic relevance in specific clinical settings, is variably expressed in most differentiated and less aggressive neuroblastic tumors, such as GN and ganglioneuroblastoma, as well as in a subset of NB cases. Gal-3 expression is associated with the INPC histopathological categorization (P<0.001) and Shimada favorable phenotype (P=0.001), but not with other prognostically relevant features. Importantly, Gal-3 expression was associated with a better 5-year overall survival (P=0.003), and with improved cumulative survival in patient subsets at worse prognosis, such as older age at diagnosis, advanced stages or NB histopathological classification. In vitro, Gal-3 expression and nuclear accumulation accompanied retinoic acid-induced cell differentiation in NB cell lines. Forced Gal-3 overexpression increased phenotypic differentiation and substrate adherence, while inhibiting proliferation. Altogether, these findings suggest that Gal-3 is a biologically relevant player for neuroblastic tumors, whose determination by conventional immunohistochemistry might be used for outcome assessment and patient's risk stratification in the clinical setting.

Rationale for hospital-based rehabilitation in obesity with comorbidities.

Severely obese patients affected by two or more chronic conditions which could mutually influence their outcome and disability can be defined as "complex" patients. The presence of multiple comorbidities often represents an obstacle for being admitted to clinical settings for the treatment of metabolic diseases. On the other hand, clinical Units with optimal standards for the treatment of pathological conditions in normal-weight patients are often structurally and technologically inadequate for the care of patients with extreme obesity. The aims of this review paper were to review the intrinsic (anthropometrics, body composition) and extrinsic (comorbidities) determinants of disability in obese patients and to provide an up-to-date definition of hospital-based multidisciplinary rehabilitation programs for severely obese patients with comorbidities. Rehabilitation of such patients require a here-and-now multidimensional, comprehensive approach, where the intensity of rehabilitative treatments depends on the disability level and severity of comorbidities and consists of the simultaneous provision of physiotherapy, diet and nutritional support, psychological counselling, adapted physical activity, specific nursing in hospitals with appropriate organizational and structural competences.