Experience of Management of Anorexia Nervosa Patients with Extremely Severe Malnutrition in a Transdisciplinary Clinical Nutrition-Eating Disorders Inpatient Unit

Background: The question of where to hospitalize extremely malnourished patients with anorexia nervosa (AN) is a real dilemma. On one hand, psychiatrists have to deal with severe medical complications that are not within their competences and that justify hospitalization in an internal medicine ward. On the other hand, medical doctors have to face psychic decompensations that would justify admission to a psychiatric ward. In this context, we share our experience of management of severely malnourished AN adult patients in a transdisciplinary specialized eating disorders (ED) unit, referral center for AN associated with somatic severity. Method: First, we described the modalities of care proposed to patients with AN hospitalized in the medical unit. Intensive medical care, both somatic and psychiatric, are provided thanks to a transdisciplinary therapeutic program, where objectives are to: medically stabilize the patient, initiate progressive refeeding and start supportive psychotherapy before being transferred to a psychiatric ED unit. Secondly, we conducted a retrospective descriptive study that included all adult patients with AN admitted for the first time to the unit, between November 1997 and January 2014, for severe malnutrition and/or complications of the ED. Objective was to specify patients’ characteristics: demographic, nutritional status, history of ED, care pathway. Results: Among a cohort of 386 adult patients with AN (21 males and 365 females) admitted for the first time in the unit, mean age was 29.4 (±11.5) years, mean BMI was 12.7 (±2.2) kg/m2. Before being supported in the unit, 78.2% of patients had already been hospitalized in other hospitals. Mean length of stay was 35.2 days. Patients were clinically serious and unstable because of life-threatening somatic complications due to a low BMI. During hospital stay, a temporary transfer to medical intensive care unit was necessary for 25.6% of patients. Average patient weight gain was 0.777 kg per week and 81.9% of patients benefited from enteral nutrition. Conclusion: This specialized transdisciplinary unit where physician nutritionists and psychiatrists coordinate medical care together, allow a better understanding and management of extreme malnutrition associated with AN. Thanks to their expertise, care teams are less critical and less rejecting towards patients. Thus, therapeutic alliance could be optimized.

Childhood asthma biomarkers including zinc: An exploratory crosssectional study

BACKGROUND Childhood bronchial asthma(BA)is a chronic inflammatory respiratory disease.Nutritional conditions,including zinc deficiency,can affect such allergic disorders.AIM To outline the difference in serum zinc levels between asthmatic children and healthy controls.METHODS A cross-sectional study was carried out at Children’s Hospital,Cairo University,investigating serum zinc levels in children with BA(n=40)and healthy children(n=21).Other markers included serum ferritin,iron,hemoglobin(Hb),and immunoglobulin E(IgE)levels.Independent t-tests and Mann-Whinny tests were used for comparisons.The Kruskal-Wallis test was applied to compare serum ferritin and IgE levels with regard to asthma severity.Spearman's rank correlation was performed to explore the relationship between serum ferritin levels and both iron and Hb levels in asthmatic children.RESULTS Children with BA had higher levels of zinc,yet the difference was not significant(P=0.115).Serum ferritin and IgE levels were significantly higher in asthmatic children(P=0.006 and 0.001,respectively),yet their levels did not differ significantly by severity(P=0.623 and 0.126,respectively).There was a nonsignificant weak correlation between serum ferritin levels and both serum iron and Hb levels.CONCLUSION Serum zinc levels do not seem to differ between asthmatic children and healthy children.Serum ferritin levels may be a marker of asthma control.Serum IgE levels are not markers of asthma severity.

Undernutrition, risk of malnutrition and obesity in gastroenterological patients: A multicenter study

AIM: To investigate the prevalence of undernutrition, risk of malnutrition and obesity in the Italian gastroenterological population. METHODS: The Italian Hospital Gastroenterology Association conducted an observational, cross-sectional multicenter study. Weight, weight loss, and body mass index were evaluated. Undernutrition was defined as unintentional weight loss > 10% in the last threesix months. Values of Malnutrition Universal Screening Tool(MUST) > 2, NRS-2002 > 3, and Mini Nutritional Assessment(MNA) from 17 to 25 identified risk of malnutrition in outpatients, inpatients and elderly patients, respectively. A body mass index ≥ 30 indicated obesity. Gastrointestinal pathologies were categorized into acute, chronic and neoplastic diseases. RESULTS: A total of 513 patients participated in the study. The prevalence of undernutrition was 4.6% in outpatients and 19.6% in inpatients. Moreover, undernutrition was present in 4.3% of the gastrointestinal patients with chronic disease, 11.0% of those with acute disease, and 17.6% of those with cancer. The risk of malnutrition increased progressively and significantly in chronic, acute and neoplastic gastrointestinal diseases in inpatients and the elderly population. Logistical regression analysis confirmed that cancer was a risk factor for undernutrition(OR = 2.7; 95%CI: 1.2-6.44, P = 0.02). Obesity and overweight were more frequent in outpatients. CONCLUSION: More than 63% of outpatients and 80% of inpatients in gastroenterological centers suffered from significant changes in body composition and required specific nutritional competence and treatment.

Hepatocellular carcinoma in nonalcoholic fatty liver: Role of environmental and genetic factors

Hepatocellular carcinoma(HCC) is the fourth cause of cancer related mortality, and its incidence is rapidly increasing. Viral hepatitis, alcohol abuse, and exposure to hepatotoxins are major risk factors, but nonalcoholic fatty liver disease(NAFLD) associated with obesity, insulin resistance, and type 2 diabetes, is an increasingly recognized trigger, especially in developed countries. Older age, severity of insulin resistance and diabetes, and iron overload have been reported to predispose to HCC in this context. Remarkably, HCCs have been reported in non-cirrhotic livers in a higher proportion of cases in NAFLD patients than in other etiologies. Inherited factors have also been implicated to explain the different individual susceptibility to develop HCC, and their role seems magnified in fatty liver, where only a minority of affected subjects progresses to cancer. In particular, the common I148 M variant of the PNPLA3 gene influencing hepatic lipid metabolism influences HCC risk independently of its effect on the progression of liver fibrosis. Recently, rare loss-of-function mutations in Apolipoprotein B resulting in very low density lipoproteins hepatic retention and in Telomerase reverse transcriptase influencing cellular senescence have also been linked to HCC in NAFLD. Indeed, hepatic stellate cells senescence has been suggested to bridge tissue aging with alterations of the intestinal microbiota in the pathogenesis of obesity-related HCC. A deeper understanding of the mechanisms mediating hepatic carcinogenesis during insulin resistance, and the identification of its genetic determinants will hopefully provide new diagnostic and therapeutic tools.

PNPLA3 I148M polymorphism and progressive liver disease

The 148 Isoleucine to Methionine protein variant(I148M)of patatin-like phospholipase domain-containing 3(PNPLA3),a protein is expressed in the liver and is involved in lipid metabolism,has recently been identified as a major determinant of liver fat content.Several studies confirmed that the I148M variant predisposes towards the full spectrum of liver damage associated with fatty liver:from simple steatosis to steatohepatitis and progressive fibrosis.Furthermore,the I148M variant represents a major determinant of progression of alcohol related steatohepatitis to cirrhosis,and to influence fibrogenesis and related clinical outcomes in chronic hepatitis C virus hepatitis,and possibly chronic hepatitis B virus hepatitis,hereditary hemochromatosis and primary sclerosing cholangitis.All in all,studies suggest that the I148M polymorphism may represent a general modifier of fibrogenesis in liver diseases.Remarkably,the effect of the I148M variant on fibrosis was independent of that on hepatic steatosis and inflammation,suggesting that it may affect both the quantity and quality of hepatic lipids and the biology of non-parenchymal liver cells besides hepatocytes,directly promoting fibrogenesis.Therefore,PNPLA3 is a key player in liver disease progression.Assessment of the I148M polymorphism will possibly inform clinical practice in the future,whereas the determination of the effect of the 148M variant will reveal mechanisms involved in hepatic fibrogenesis.

Assessment of small intestinal bacterial overgrowth in uncomplicated acute diverticulitis of the colon

AIM: Small intestinal bacterial overgrowth (SIBO) maycontribute to the appearance of several gastrointestinal nonspecific symptoms. Acute diverticulitis is affected by some similar symptoms and bacterial colonic overgrowth. We assessed the prevalence of SIBO in acute uncomplicated diverticulitis and evaluated its influence on the clinical course of the disease.METHODS: We studied 90 consecutive patients (39 males, 51 females, mean age 67.2 years, range 32-91 years). Sixty-one patients (67.78%) and 29 patients (32.22%) were affected by constipation-or diarrhea-prevalent diverticulitis respectively. All subjects were investigated by lactulose H2-breath test at the entry and at the end of treatment. We also studied a control group of 20 healthy subjects (13 males, 7 females, mean age 53 years, range 22-71 years).RESULTS: Oro-cecal transit time (OCTT) was delayed in67/90 patients (74.44%) (range 115-210 min, mean 120 min). Fifty-three of ninety patients (58.88%) showed SIBO, while OCTT was normal in 23/90 patients (25, 56%). In the control group, the mean OCTT was 88.2 min (range 75-135 min). The difference between diverticulitic patients and healthy subjects was statistically significant (P＜0.01). OCTT was longer in constipation-prevalent disease than in diarrheaprevalent disease [180.7 min (range 150-210 min) vs 121 min (range 75-180 min) (P＜0.001)], but no difference in bacterial overgrowth was found between the two forms of diverticulitis.After treatment with rifaximin plus mesalazine for 10 d, followed by mesalazine alone for 8 wk, 70 patients (81.49%) were completely asymptomatic, while 16 patients (18.60%) showed only slight symptoms. Two patients (2.22%) had recurrence of diverticulitis, and two other patients (2.22%) were withdrawn from the study due to side-effects. Seventy-nine of eighty-six patients (91.86%) showed normal OCTT (range 75-105 min, mean 83 min), while OCTT was longer, but it was shorter in the remaining seven (8.14%) patients (range 105-115 min, mean of 110 min). SIBO was eradicated in all patients, while it persisted in one patient with recurrence of diverticulitis. CONCLUSION: SIBO affects most of the patients with acute diverticulitis. SIBO may worsen the symptoms of patients and prolong the clinical course of the disease, as confirmed in the case of persistence of SIBO and diverticulitis recurrence. In this case, we can hypothesize that bacteria from small bowel may re-colonize in the colon and provoke recurrence of symptoms.

Assessment of autonomic function in untreated adult coeliac disease

AIM: Some recent studies showed that alteration of upper-gut motility in coeliac disease may be related to dysfunction of autonomic nervous system. The aim of our study was to investigate whether autonomic nervous system was altered in untreated and unselected coeliac disease patients.METHODS: We studied 8 untreated and consecutive coeliac disease patients (2 males and 6 females, age range 37±14.5 years). Histological evaluation of duodenal mucosa, anti-gliadin antibodies (AGA), antiendomysial antibodies (EMA) and anti-tTG antibodies and sorbitol H2 breath test were performed in all patients. Extrinsic autonomic neuropathy was assessed by the standardized measurement of cardiovascular reflexes (lying-to-standing,Valsalva manoeuvre, deep breathing, sustained handgrip).The results obtained were compared with a healthy,asymptomatic control group (6 males and 7females, age range 42.3±13.5 years).RESULTS: Coeliac patients exhibited a lower increase of PAS as a response to isometric effort, a reduction of spectral power LF as a response to clinostatic position,but without statistical significance. Also they showed a lower tolerance to orthostatic position, associated with a latent disequilibrium of sympathetic-vagal balance, a relative prevalence of parasympathetic component of the autonomic function. However, these results were not statistically significant when compared with control group(P = n.s.). And they were unchanged after 6 and 12 mo of gluten-free diet.CONCLUSION: This study failed to confirm a significant correlation between autonomic dysfunction and coeliac disease, yet we could not exclude a role of autonomic dysfunction in the genesis of systemic symptoms in some coeliacs.

Inflammatory Bowel Diseases: What Do We Still Need to Investigate?

Inflammatory bowel disease (IBD) including Crohn (CD) and ulcerative colitis (UC), is intestinal disorders with an unknown specific etiology. Many factors are involved in the pathogenesis: genetic, environment, nutrition, immunity and intestinal dysbiosis. In the present work, we review the most important trigger mechanisms involved in IBD, with a particular regard to the role of microbiota and fecal mass transplantation as a new therapeutic approach, that even if it can be considered safe and effective, data are necessary regarding all procedures not yet standardized and timing of treatment.

Non-alcoholic fatty liver disease:Dietary and nutraceutical approaches

Non-alcoholic fatty liver disease(NAFLD),defined as the presence of fat accumulation in imaging or histology in more than 5%of hepatocytes and exclusion of other causes for secondary hepatic fat accumulation,is one of the major causes of chronic liver disease worldwide.Metabolic syndrome is associated with an increased risk of progression from NAFLD to non-alcoholic steatohepatitis(NASH),fibrosis,and forthcoming liver failure.Also,genetic predisposition contributes to the risk of NAFLD development.This review explores the role of diets and nutraceuticals in delaying the development and the evolution of NAFLD to chronic liver disease.The Mediterranean diet,high-protein diet,lowcarbohydrate/high-fat diet,high-carbohydrate/low-fat diet,and intermittent fasting are the dietary approaches investigated given the presence of relevant literature data.Moreover,this review focused on nutraceuticals with proven efficacy in ameliorating NAFLD and grouped them into four different categories:plant-based nutraceuticals(Ascophyllum nodosum and Fucus vesiculosus,Silymarin,Berberine,Curcumin,Resveratrol,Nigella sativa,Quercetin),vitamin-like substances(vitamin E,vitamin D,vitamin C,coenzyme Q10,inositol),fatty acids(omega-3),and microbiota-management tools(probiotics).

Chemotherapy for Hepatocellular Carcinoma: Current Evidence and Future Perspectives

Hepatocarcinogenesis is a multistep process,heralded by abnormalities in cell differentiation and proliferation and sustained by an aberrant neoangiogenesis.Understanding the underlying molecular pathogenesis leading to hepatocellular carcinoma is a prerequisite to develop new drugs that will hamper or block the steps of these pathways.As hepatocellular carcinoma has higher arterial vascularization than normal liver,this could be a good target for novel molecular therapies.Introduction of the antiangiogenic drug sorafenib into clinical practice since 2008 has led to new perspectives in the management of this tumor.The importance of this drug lies not only in the modest gain of patients' survival,but in having opened a roadmap towards the development of new molecules and targets.Unfortunately,after the introduction of sorafenib,during the last years,a wide number of clinical trials on antiangiogenic therapies failed in achieving significant results.However,many of these trials are still ongoing and promise to improve overall survival and progression-free survival.A recent clinical trial has proven regorafenib effective in patients showing tumor progression under sorafenib,thus opening new interesting therapeutic perspectives.Many other expectations have been borne from the discovery of the immune checkpoint blockade,already known in other solid malignancies.Furthermore,a potential role in hepatocellular carcinoma therapy may derive from the use of branched-chain amino acids and of nutritional support.This review analyses the biomolecular pathways of hepatocellular carcinoma and the ongoing studies,the actual evidence and the future perspectives concerning drug therapy in this open field.

The mechanism of dysbiosis in alcoholic liver disease leading to liver cancer

Currently, alcoholic liver disease (ALD) is one of the most prevalent chronic liver diseases worldwide, representing one of the main etiologies of cirrhosis and hepatocellular carcinoma (HCC). Although we do not know the exact mechanisms by which only a selected group of patients with ALD progress to the final stage of HCC, the role of the gut microbiota within the progression to HCC has been intensively studied in recent years. To date, we know that alcohol-induced gut dysbiosis is an important feature of ALD with important repercussions on the severity of this disease. In essence, an increased metabolism of ethanol in the gut induced by an excessive alcohol consumption promotes gut dysfunction and bacterial overgrowth, setting a leaky gut. This causes the translocation of bacteria, endotoxins, and ethanol metabolites across the enterohepatic circulation reaching the liver, where the recognition of the pathogen-associated molecular patterns via specific Toll-like receptors of liver cells will induce the activation of the nuclear factor kappa-B pathway, which releases pro-inflammatory cytokines and chemokines. In addition, the mitogenic activity of hepatocytes will be promoted and cellular apoptosis will be inhibited, resulting in the development of HCC. In this context, it is not surprising that microbiota-regulating drugs have proven effectiveness in prolonging the overall survival of patients with HCC, making attractive the implementation of these drugs as co-adjuvant for HCC treatment.