Severity Of Weight Loss Research Articles

An examination of adults with atypical anorexia nervosa at admission to treatment at higher levels of care: An attempt to increase diagnostic clarity.

Anorexia nervosa (AN) is a serious illness with a high mortality rate and multiple physiological complications. The vague definition of atypical AN allows for subjective interpretation. This retrospective study aimed to focus future research on the operational definition of atypical AN by examining four factors associated with atypical AN at admission to higher level of care treatment. Adults with atypical AN (n = 69) were examined within sample analyses among four groups: (1) >10% versus ≤10% weight loss; (2) weight loss within the previous 3 months versus >3 months; (3) engaging in purging behaviors versus absence of purging behaviors; and (4) endorsing versus not endorsing significant cognitive aspects of AN. Patients with atypical AN endorsed elevated ED cognitions on the Eating Disorder Examination-Questionnaire and depressive symptoms; a lack of association was found between weight loss severity and weight loss time frame with depressive symptoms, eating concern, and restraint. Purging behavior was associated with a higher expected body weight percentage (%EBW) and dietary restraint, while greater AN cognitions were associated with a higher EBW and weight loss percentage. Few patients demonstrated bradycardia, hypophosphatemia, or amenorrhea. This study demonstrated the severity of ED cognitions and depressive symptoms in this atypical AN sample and provided directions for future studies in the nosology of atypical AN. It may be important to distinguish between individuals with atypical AN who are purging and those who are not. Atypical AN was associated with a low frequency of physiological disturbances. This study provides further clarification regarding the operational definition of atypical AN; currently, a constellation of symptoms under Other Specified Feeding or Eating Disorders. This study was consistent with previous research in reporting severe eating disorder cognitions in adults with atypical AN, and noted the potential importance of distinguishing a purging distinction. A minority of patients in this study had physiological impairments.

Distinguishing probable atypical anorexia nervosa from weight loss alone in a national sample of U.S. Military Veterans: Disentangling the roles of weight suppression and cognitive concerns.

Veterans are at high risk for eating disorders (EDs), and specifically for atypical anorexia nervosa (atypical AN). The current study aimed to better understand this under-studied disorder and how it differs from weight loss without ED cognitive features. Secondary analyses were conducted with data from a national study of Veterans (N = 882, 49.4% women). Participants were categorized into four mutually exclusive groups using the Eating Disorder Diagnostic Scale 5: probable atypical AN, a cognitive concerns group (Cog Only), a weight suppressed group (WS Only), and a no ED control group. Adjusted regression models were used to compare groups on measures of eating pathology and mental health. Three weight suppression thresholds (5%, 10%, and 15%) for probable atypical AN were also tested. The sample was comprised of 12% probable atypical AN, 23.6% Cog Only, 16.3% WS Only, and 48.1% Control. The probable atypical AN group was most like the Cog Only group except for higher levels of dietary restraint. Atypical AN fared worse and was least like the Control group followed by the WS Only group. All weight suppression thresholds significantly predicted dietary restraint, with 5% being the best predictor. Results found that probable atypical AN is a distinct clinical entity and that the exact weight suppression threshold associated with atypical AN is less important than having any weight suppression. Findings highlight the clinical significance of atypical AN and the importance of gaining a better understanding of how to address this clinical entity. Atypical anorexia nervosa is a relatively underexamined but highly prevalent eating disorder in the Veteran population. Results show that ED cognitive features are more closely linked to clinically significant eating pathology and poor mental health than weight suppression alone suggesting that negative thinking about weight gain and appearance, regardless of the presence or severity of weight loss, may signal the need for specialized intervention.

Impacts of xylazine on fentanyl demand, body weight, and acute withdrawal in rats: A comparison to lofexidine

The opioid use landscape has recently shifted to include xylazine, a veterinary anesthetic, as an adulterant in the fentanyl supply. The health impacts of xylazine as an emerging fentanyl adulterant has raised alarm regarding xylazine as a public health threat, warranting research on the impacts of xylazine on fentanyl's behavioral effects. No prior studies have evaluated the effects of xylazine on fentanyl consumption at various unit doses, fentanyl demand, or withdrawal as compared to the Food and Drug Administration-approved opioid withdrawal medication, lofexidine (Lucemyra®). This is important because lofexidine and xylazine are both adrenergic α2a (A2aR) agonists, however, lofexidine is not a noted fentanyl adulterant. Here we evaluated xylazine and lofexidine combined with self-administered fentanyl doses in male and female rats and evaluated fentanyl demand, body weight, and acute withdrawal. Consumption of fentanyl alone increased at various unit doses compared to saline. Xylazine but not lofexidine shifted fentanyl consumption downward at a number of unit doses, however, both lofexidine and xylazine suppressed fentanyl demand intensity as compared to a fentanyl alone control group. Further, both fentanyl + lofexidine and fentanyl + xylazine reduced behavioral signs of fentanyl withdrawal immediately following SA, but signs increased by 12 h only in the xylazine co-exposed group. Weight loss occurred throughout fentanyl SA and withdrawal regardless of group, although the xylazine group lost significantly more weight during the first 24 h of withdrawal than the other two groups. Severity of weight loss during the first 24 h of withdrawal was also correlated with severity of somatic signs of fentanyl withdrawal. Together, these results suggest that body weight loss may be an important indicator of withdrawal severity during acute withdrawal from the xylazine/fentanyl combination, warranting further translational evaluation.

Impact of comorbidity scores and lifestyle factors in curative radiotherapy in laryngeal cancer.

The principal goal of treatment of laryngeal cancer is to eliminate atumour while preserving laryngeal function with radio(chemo)therapy being the mainstay of treatment. The aim of this report is to present the influence of comorbidities and lifestyle factors on treatment outcomes in our cohort of patients. During the period 2009-2018, curative radio(chemo)therapy for laryngeal cancer was performed on 189patients. The median OS was 50.8months, with amean PFS of 96.5months, mean LC of 101.4months and amedian follow-up of 38.1months. Acute and late treatment toxicity grade 3-4 was observed in 39.2% patients and 10.1% patients, respectively. Asignificant effect on overall survival was confirmed for the baseline PS (performance status), severity of weight loss, baseline haemoglobin values, history of alcohol abuse, marital status and comorbidities according to the Charlson Comorbidity Index, as well as the ACE-27 and ASA scores. In our cohort of patients treated with radio(chemo)therapy for laryngeal cancer, we found good therapeutic results and an acceptable side-effect profile. Statistically significant predictors of overall survival were the baseline PS, weight loss, anaemia, associated comorbidities, history of alcohol abuse and marital status.

Severity Level and Duration of Energy Deficit in Mice Affect Bone Phenotype and Bone Marrow Stromal Cell Differentiation Capacity.

Anorexia nervosa is known to induce changes in bone parameters and an increase in bone marrow adiposity (BMA) that depend on the duration and seriousness of the disease. Previous studies have found that bone loss is associated with BMA accumulation. Sirtuin of type 1 (Sirt1), a histone deacetylase that is partly regulated by energy balance, was shown to have pro-osteoblastogenic and anti-adipogenic effects. To study the effects of the severity and duration of energy deficits related to bone loss, a mouse model of separation-based anorexia (SBA) was established. We recently demonstrated that moderate body weight loss (18%) 8-week SBA protocol in mice resulted in an increase in BMA, bone loss, and a significant reduction in Sirt1 expression in bone marrow stromal cells (BMSCs) extracted from SBA mice. We hypothesised that Sirt1 deficit in BMSCs is associated with bone and BMA alterations and could potentially depend on the severity of weight loss and the length of SBA protocol. We studied bone parameters, BMA, BMSC differentiation capacity, and Sirt1 expression after induction of 4 different levels of body weight loss (0%,12%,18%,24%), after 4 or 10 weeks of the SBA protocol. Our results demonstrated that 10 week SBA protocols associated with body weight loss (12%, 18%, 24%) induced a significant decrease in bone parameters without any increase in BMA. BMSCs extracted from 12% and 18% SBA groups showed a significant decrease in Sirt1 mRNA levels before and after co-differentiation. For these two groups, decrease in Sirt1 was associated with a significant increase in the mRNA level of adipogenic markers and a reduction of osteoblastogenesis. Inducing an 18% body weight loss, we tested a short SBA protocol (4-week). We demonstrated that a 4-week SBA protocol caused a significant decrease in Tb.Th only, without change in other bone parameters, BMA, Sirt1 expression, or differentiation capacity of BMSCs. In conclusion, this study showed, for the first time, that the duration and severity of energy deficits are critical for changes in bone parameters, BMSC differentiation, and Sirt1 expression. Furthermore, we showed that in this context, Sirt1 expression could impact BMSC differentiation with further effects on bone phenotype.

MRI-Determined Psoas Muscle Fat Infiltration Correlates with Severity of Weight Loss during Cancer Cachexia.

Simple SummaryDuring cancer cachexia, patients experience profound weight loss due to metabolic dysfunction, resulting in muscle composition alterations. The proton density fat fraction (PDFF) using magnetic resonance imaging (MRI) is an established biomarker to assess changes of muscle composition. We evaluated the suitability of MRI-determined psoas and erector spinae muscle PDFF and fat volume as biomarkers for monitoring cachexia development in an oncological cohort of 58 patients and assessed the regional variation in muscle parameters over time. Our results indicate that psoas muscle PDFF and fat volume could serve as MRI-determined biomarkers for early risk stratification and disease monitoring regarding progression and severity of weight loss in cancer cachexia.Purpose: To evaluate the suitability of psoas and erector spinae muscle proton density fat fraction (PDFF) and fat volume as biomarkers for monitoring cachexia severity in an oncological cohort, and to evaluate regional variances in muscle parameters over time. Methods: In this prospective study, 58 oncological patients were examined by a 3 T MRI receiving between one and five scans. Muscle volume and PDFF were measured, segmentation masks were divided into proximal, middle and distal muscle section. Results: A regional variation of fat distribution in erector spinae muscle at baseline was found (p < 0.01). During follow-ups significant relative change of muscle parameters was observed. Relative maximum change of erector spinae muscle showed a significant regional variation. Correlation testing with age as a covariate revealed significant correlations for baseline psoas fat volume (r = −0.55, p < 0.01) and baseline psoas PDFF (r = −0.52, p = 0.02) with maximum BMI change during the course of the disease. Conclusion: In erector spinae muscles, a regional variation of fat distribution at baseline and relative maximum change of muscle parameters was observed. Our results indicate that psoas muscle PDFF and fat volume could serve as MRI-determined biomarkers for early risk stratification and disease monitoring regarding progression and severity of weight loss in cancer cachexia.

Weight Loss as an Untapped Early Detection Marker in Pancreatic and Periampullary Cancer.

Pancreatic ductal adenocarcinoma (PDAC) has the worst survival of common cancers, partly because there are no reliable early detection tests. Unintentional weight loss (≥ 5% decrease from baseline) has been linked to PDAC, but the frequency and severity of weight loss using objective measures, and its relationship to prognosis, have not been well characterized. We identified 390 patients with PDAC (all stages) and two or more prediagnosis weights in the electronic medical record. Percentage weight loss in the 365 and 180days preceding diagnosis was calculated. Results were compared with raw weights of age- and sex-matched non-cancer controls (n=780). Odds ratios for PDAC were calculated using conditional logistic regression. Cox proportional hazards models were used for survival. Within 1year of diagnosis, more PDAC patients lost ≥ 5% weight relative to controls (74.9% vs. 11.2%; p<0.001), with a median weight loss of 14.2 versus 2.9lbs. The odds ratio for PDAC comparing weight loss within 1year of 5 to < 10% was 10.30 (p<0.001) and 77.82 for ≥ 10% (p<0.001), compared with stable weight. Weight loss prior to diagnosis was also associated with early-stage PDAC. PDAC cases with ≥ 10% prediagnosis weight loss had worse survival compared with stable weights (hazard ratio [HR] 1.60; p=0.01). Greater prediagnosis weight loss was associated with poor survival after pancreatectomy (5 to < 10% vs. < 5%, HR 2.40, p=0.03; ≥ 10% vs. < 5%, HR 2.59, p=0.03). Diagnosis of PDAC is preceded by unintentional weight loss in the majority of patients, even at an early stage. Greater prediagnosis weight loss severity is also associated with poor postoperative survival.

Nutritional Issues in Head and Neck Cancer Patients.

The purpose of this paper is to update the oncologist on the correct approach to the nutritional care of the head and neck cancer patient. Recent scientific contributions on this issue, with a special emphasis on international guidelines and randomised clinical trials (RCTs), are reviewed. The following points are noteworthy: 1. Despite the advances in early diagnosis and modern treatment of head and neck cancer, this tumour still ranks first regarding frequency and severity of weight loss, both at the clinical presentation and during the therapy. 2. This is due to the combination of poor alimentation because of the tumour mass localization, as well as of the presence of an inflammatory response which furtherly drives catabolism. 3. Several studies have shown a very limited role for a dietary counselling unless it includes oral nutritional supplements which are protein or omega-3 fatty acid enriched. 4. A parental nutritional supplementation could represent an acceptable short-term alternative. 5. Long-term nutritional support relies on the use of percutaneous endoscopic gastrostomy (PEG), whereas the role of a prophylactic or “a la demande” PEG is still unsettled and requires further investigations. In conclusion, the nutritional approach using specific formulas and the appropriate route of administration should be part of the therapeutic armamentarium of the modern oncologist.

Higher Nutritional Status of Lung Cancer Cachexia Patients is Associated with Higher Functional Capacity and Appetite

Introduction: Lung cancer is highly prevalent and the major cause of cancer-related deaths worldwide. Severity of weight loss has been shown to have a negative impact on patients’ performance and quality of life. Early detection of anorexia and decline of functional capacity will be very usefull to prevent severe weight loss and a better prognosis. Methods: A cross sectional study was conducted in Dharmais Cancer Hospital. Subjects were lung cancer patients newly diagnosed or a minimal of 2 months pasca chemotherapy or radiotherapy, taken consecutively from inpatients and outpatients. Results: Subjects eligible for the study were 47, with a composition of 55.3% men and 44.7% women in the age range from 36–79 years old. There were significant relationship between body weight and BMI with ECOG score. Body weight, BMI and weight loss related significantly with VAS appetite and SNAQ score. These result indicate that subjects with a higher BMI and a lower weight loss have a better physical performa and appetite. There were significant relation between haemoglobin level, anemia status and serum albumin level with appetite and risk for anorexia. This result indicate that subjects with normal haemoglobin and albumin have a good appetite and a lower risk for anorexia. Conclusions: Positive prognosis of cancer patients can be obtained by maintaining BMI and preventing weight loss, since both affected the already known prognostic marker functional capacity significantly. Serum Albumin and hemoglobin are not only simple test, but also brings benefits, a clinical marker that may be used to assess the risk of anorexia.

Villus Growth, Increased Intestinal Epithelial Sodium Selectivity, and Hyperaldosteronism Are Mechanisms of Adaptation in a Murine Model of Short Bowel Syndrome

BackgroundShort bowel syndrome results from extensive small bowel resection and induces adaptation of the remaining intestine. Ileocecal resection (ICR) is the most frequent situation in humans. Villus hypertrophy is one hallmark of mucosal adaptation, but the functional mechanisms of mucosal adaptation are incompletely understood.AimsThe aim of the study was to characterize a clinically relevant model of short bowel syndrome but not intestinal failure in mice and to identify outcome predictors and mechanisms of adaptation.MethodsMale C57BL6/J mice underwent 40% ICR and were followed for 7 or 14 days. Small bowel transection served as control. All mice underwent autopsy. Survival, body weight, wellness score, stool water content, plasma aldosterone concentrations, and paracellular permeability were recorded.ResultsUnlike controls, resected mice developed significant diarrhea with increased stool water. This was accompanied by sustained weight loss throughout follow-up. Villus length increased but did not correlate positively with adaptation. Plasma aldosterone concentrations correlated inversely with body weight at day 14. After ICR, intestinal epithelial (i.e., tight junctional) sodium permeability was increased.Conclusions40% ICR results in moderate to severe short bowel syndrome. Successful adaptation to the short bowel situation involves villus elongation but does not correlate with the degree of villus elongation alone. In addition, increased intestinal epithelial sodium permeability facilitates sodium-coupled solute transport. Hyperaldosteronism correlates with the severity of weight loss, indicates volume depletion, and counterregulates water loss.

Effects of nutrition factors on mortality and sepsis occurrence in a multicenter university-based surgical intensive care unit in Thailand (THAI-SICU study).

The aim of this study was to demonstrate the role of nutrition factors on a 28-d mortality outcome and sepsis occurrence in surgical intensive care unit. The data was extracted from a THAI-SICU study that prospectively recruited participants (≥18 y of age) from three Thai surgical intensive care units (SICUs) of university-based hospitals. The demographic data and nutrition factors at SICU admission included energy delivery deficit, weight loss severity, route of energy delivery, and albumin and nutrition risk screening (NRS-2002). The outcomes were 28-d hospital mortality and sepsis occurrence. The statistical analysis was performed using Cox regression. The study included 1503 eligible patients with a predominantly male population. The 28-d mortality and sepsis occurrences were 211 (14%) and 452 (30%), respectively. Regarding multivariable analysis, for mortality outcome, the protective effects of nutrition variables were higher body mass index (BMI; hazard ratio [HR], 0.82; 95% confidence interval [CI], 0.68-0.99; P = 0.039), tube feeding (HR, 0.46; 95% CI, 0.26-0.83; P = 0.010), and a combination of enteral and parenteral nutrition (HR, 0.24; 95% CI, 0.07-0.77; P = 0.016). The harmful effects were severe weight loss (HR, 1.61; 95% CI, 1.16-2.22; P = 0.004), albumin ≤2.5 (HR, 2.15; 95% CI, 1.20-3.84; P = 0.010), and at risk according to NRS-2002 (HR, 1.34; 95% CI, 0.98-1.85; P = 0.071). For the sepsis occurrence, only tube feeding had a protective effect (HR, 0.58; 95% CI, 0.39-0.88; P = 0.009), and only albumin ≤2.5 had a harmful effect (HR, 1.71; 95% CI, 1.20-2.45; P = 0.003). Nutrition factors affecting the mortality or sepsis occurrence in this study were BMI, enteral feeding or combination with parenteral nutrition, severe weight loss, preadmission albumin ≤2.5, and at risk according to NRS-2002.

Post-diagnosis weight loss as a prognostic factor in non-small cell lung cancer.

BackgroundCachexia and its most visible manifestation, weight loss, represent important poor prognostic factors for patients with non‐small cell lung cancer. This work examines how severity of weight loss as an indicator of cachexia affects outcomes.MethodsIn a retrospective observational study of electronic medical records, patients with non‐small cell lung cancer were monitored for weight loss from an initial assessment (within 2 months of index diagnosis) to a landmark at 5 months (at least 3 months after initial assessment). Patients who survived to the landmark were then followed to determine the association of baseline body mass index (BMI) and weight loss during the assessment period with outcomes. Patients were clustered to determine how BMI and weight loss related to survival as approximated by time of last appearance in the database, a strong proxy for time of death.ResultsTwelve thousand one hundred and one patients were divided into 5 cachexia risk groups based on a combination of weight loss and initial BMI. More severe groups demonstrated progressively worse outcomes, with the most severe group surviving for a median of 263 days (95% CI 254–274) from index and having a 1‐year survival rate of 31%. The least severe group survived for a median of 825 days from index (95% CI 768–908) and had a 1‐year survival rate of 78%. Cachexia risk group was a stronger predictor of survival than any baseline variable, including disease stage, performance status, or age.ConclusionsIn this study, we showed that increasing weight loss and, to a lesser extent, decreasing BMI, led to substantially worse outcomes for non‐small cell lung cancer patients independent of other variables. We suggest risk score groups that provide an improved approach for identifying poor prognosis patients with the greatest need.

Posttonsillectomy weight loss in adults.

To analyze and determine the incidence and severity of weight loss in adult tonsillectomies. Case series with chart review. Adult tonsillectomy is performed for a variety of indications. Anecdotally, patients report a 10- to 15-pound weight loss in the postoperative period; however, no supporting research has been documented. The pediatric population has a well-documented weight gain postoperatively. In total, 138 adults (aged 18-40 years) receiving tonsillectomy at Naval Medical Center Portsmouth (NMCP) between 2008 and 2013. A retrospective study was performed using an S3 surgery scheduling system search of all adult tonsillectomies at NMCP between 2008 and 2013. A subsequent electronic medical record search (AHLTA) of preoperative and postoperative weights and demographics was performed. Data analysis revealed a significant difference found between preoperative and postoperative weight across all age groups (4.77 pounds, P < .005). Analysis of variance was performed to determine if there is a significant difference between these age and body mass index (BMI) groups. The highest amount of weight loss was observed in the oldest population group (5.72 pounds in subjects aged >40 years, 4.95 pounds in 31- to 40-year-olds, and 5.44 pounds in 20- to 30-year-olds, P = .03). Age comparisons were statistically significant. There was no statistically significant association between BMI and postoperative weight loss. These results indicate that there is evidence of a roughly 5-pound weight loss in the postoperative period following tonsillectomy in adults with subsequent return to baseline weight after roughly 5 months. These findings are significant since this could lead to further research into changes in obesity-associated disease.

Treatments of medical complications of anorexia nervosa and bulimia nervosa.

Inherent to anorexia nervosa and bulimia nervosa are a plethora of medical complications which correlate with the severity of weight loss or the frequency and mode of purging. Yet, the encouraging fact is that most of these medical complications are treatable and reversible with definitive care and cessation of the eating-disordered behaviours. Herein, these treatments are described for both the medical complications of anorexia nervosa and those which are a result of bulimia nervosa.

Cachexia: clinical features when inflammation drives malnutrition.

Cachexia is a clinically relevant syndrome which impacts on quality of life, morbidity and mortality of patients suffering from acute and chronic diseases. The hallmark of cachexia is muscle loss, which is triggered by disease-associated inflammatory response. Cachexia is a continuum and therefore a staging system is needed. Initially, a three-stage system (i.e. pre-cachexia, cachexia and refractory cachexia) was proposed. More recent evidence supports the use of a five-stage classification system, based on patient's BMI and severity of weight loss, to better predict clinical outcome. Also, large clinical trials in cancer patients demonstrated that cachexia emerging during chemotherapy has greater influence on survival than weight loss at baseline. Therefore, becoming widely accepted is the importance of routinely monitoring patients' nutritional status to detect early changes and diagnose cachexia in its early phases. Although cachexia is associated with the presence of anabolic resistance, it has been shown that sustained yet physiological hyperaminoacidaemia, as well as the use of specific nutrients, is able to overcome impaired protein synthesis and revert catabolism. More importantly, clinical evidence demonstrates that preservation of nutritional status during chemotherapy or improvement of body weight after weight loss is associated with longer survival in cancer patients.

Anamorelin for patients with cancer cachexia: an integrated analysis of two phase 2, randomised, placebo-controlled, double-blind trials

Cancer anorexia-cachexia syndrome is associated with increased morbidity and mortality. Anamorelin is an oral ghrelin-receptor agonist with appetite-enhancing and anabolic activity. We assessed the effects of anamorelin on body composition, strength, quality of life, biochemical markers, and safety in patients with cancer anorexia-cachexia. Data were pooled, a priori, from two completed phase 2, multicentre, placebo-controlled, double-blind trials in patients with advanced or incurable cancer and weight loss of 5% or more. Patients were stratified by weight loss severity (5-15%, >15%) and randomly allocated (1:1) with a computer-generated randomisation schedule to anamorelin hydrochloride 50 mg or placebo once-daily for 12 weeks. Primary outcome was lean body mass by dual-energy x-ray absorptiometry over the 12 week treatment period in eligible patients who had at least one dose of study drug and post-treatment efficacy assessment. We assessed safety in all patients who received at least one dose of study drug. The trials are registered with ClinicalTrials.gov, numbers NCT00219817 and NCT00267358. Between June 29, 2005, and Oct 26, 2006, we enrolled 44 patients in the anamorelin group and 38 patients in the placebo group. 74 patients were eligible for the efficacy analyses. Over 12 weeks, lean body mass increased in 38 patients in the anamorelin group by a least-squares mean of 1.89 kg (95% CI 0.84 to 2.95) compared with a decrease of a least-squares mean of -0.20 kg (-1.23 to 0.83) for 36 patients in the placebo group (difference 2.09 kg [0.94-3.25]; p=0.0006). 42 (95%) of 44 patients treated with anamorelin and 33 (87%) of 38 patients treated with placebo had adverse events. The most common grade 3-4 adverse events (treatment-related or not) in the anamorelin group were fatigue, asthenia, atrial fibrillation, and dyspnoea (two [5%] each); in the placebo group, such events were pneumonia (three [8%]) and anaemia, thrombocytopenia, abdominal pain, anxiety, and dyspnoea (two [5%] each). Anamorelin treatment for 12 weeks had a favourable clinical response profile in patients with cancer anorexia-cachexia syndrome. These findings support further investigation in this setting. Helsinn Therapeutics (US), Helsinn Healthcare SA.

Lysophosphatidic acid increases SLC26A3 expression in inflamed intestine and reduces diarrheal severity in C57BL/6 mice with dextran-sodium-sulfate-induced colitis

Background Diarrhea is a common clinical feature of ulcerative colitis resulting from unbalanced intestinal fluid and salt absorption and secretion. The Cl-/HCO3 - exchanger SLC26A3 is strongly expressed in the mid-distal colon and plays an essential role in colonic Cl- absorption and HCO3 - secretion. Slc26a3 expression is up-regulated by lysophosphatidic acid (LPA)in vitro. Our study was designed to investigate the effects of LPA on SLC26A3 expression and the diarrheal phenotype in a mouse colitis model. Methods Colitis was induced in C57BL/6 mice by adding 4% of dextran sodium sulfate (DSS) to the drinking water. The mice were assigned to LPA treatment DSS group, phosphate-buffered saline (PBS) treatment DSS group, DSS only group and untreated mice with a completely randomized design. Diarrhea severity was evaluated by measuring mice weight, disease activity index (DAI), stool water content and macroscopic evaluation of colonic damage. The effect of LPA treatment on Slc26a3 mRNA level and protein expression in the different groups of mice was investigated by quantitative PCR and Western blotting. Results All mice treated with DSS lost weight, but the onset and severity of weight loss was attenuated in the LPA treatment DSS group. The increases in stool water content and the macroscopic inflammation score in LPA treatment DSS group were significantly lower compared to DSS control group or PBS treatment DSS group ((18.89±8.67)% vs. (28.97±6.95)% or (29.48±6.71)%, P=0.049, P=0.041, respectively and 2.67±0.81 vs. 4.5±0.83 or 4.5±0.54, P=0.020, P=0.006, respectively), as well as the increase in DAI (P=0.004, P=0.008, respectively). LPA enema resulted in higher Slc26a3 mRNA and protein expression levels compared to PBS-treated and untreated DSS colitis mice. Conclusion LPA increases Slc26a3 expression in the inflamed intestine and reduces diarrhea severity in DSS-induced colitis, suggesting LPA might be a therapeutic strategy in the treatment of colitis associated diarrhea.

Eating Disorders and Risk of Death

Eating Disorders and Risk of Death

Relationship between Affective Symptoms and Malnutrition Severity in Severe Anorexia Nervosa

BackgroundVery few studies have investigated the relationship between malnutrition and psychological symptoms in Anorexia Nervosa (AN). They have used only body weight or body mass index (BMI) for the nutritional assessment and did not always report on medication, or if they did, it was not included in the analysis of results, and they did not include confounding factors such as duration of illness, AN subtype or age. The present study investigates this relationship using indicators other than BMI/weight, among which body composition and biological markers, also considering potential confounders related to depression and anxiety.Methods155 AN patients, (DSM-IV) were included consecutively upon admission to inpatient treatment. Depression, anxiety, obsessive behaviours and social functioning were measured using various scales. Nutritional status was measured using BMI, severity of weight loss, body composition, and albumin and prealbumin levels.ResultsNo correlation was found between BMI at inclusion, fat-free mass index, fat mass index, and severity of weight loss and any of the psychometric scores. Age and medication are the only factors that affect the psychological scores. None of the psychological scores were explained by the nutritional indicators with the exception of albumin levels which was negatively linked to the LSAS fear score (p = 0.024; beta = −0.225). Only the use of antidepressants explained the variability in BDI scores (p = 0.029; beta = 0.228) and anxiolytic use explained the variability in HADs depression scores (p = 0.037; beta = 0.216).ConclusionThe present study is a pioneer investigation of various nutritional markers in relation to psychological symptoms in severely malnourished AN patients. The clinical hypothesis that malnutrition partly causes depression and anxiety symptoms in AN in acute phase is not confirmed, and future studies are needed to back up our results.

Intramyocellular lipid droplets increase with progression of cachexia in cancer patients

BackgroundIntramyocellular lipids are an important source of fuel for mitochondrial fat oxidation and play an important role in intramuscular lipid homeostasis. We hypothesised that due to the phenotype associated with cancer cachexia, there would exist an association between increasing weight loss and the number/size of intramyocellular lipid droplets.MethodsNineteen cancer patients and 6 controls undergoing surgery were recruited. A rectus abdominis biopsy was performed and processed for transmission electron microscopy (TEM). The number of intramyocellular lipid droplets and lipid droplet diameter were calculated from the TEM images. CT scans, performed as part of patients' routine care, were analysed to determine amount of adipose (intermuscular, visceral and subcutaneous) and muscle tissue.ResultsCompared with controls, cancer patients had increased numbers of lipid droplets (mean (SD) 1.8 (1.9) vs. 6.4 (9.1) per ×2,650 field, respectively, p = 0.036). Mean (SD) lipid droplet diameter was also higher in cancer patients compared with controls (0.42 (0.13) vs. 0.24 (0.21) μm, p = 0.015). Mean lipid droplet count correlated positively with the severity of weight loss (R = 0.51, p = 0.025) and negatively with CT-derived measures of intermuscular fat (R = −0.53, p = 0.022) and visceral fat (R = −0.51, p = 0.029).ConclusionsThis study suggests that the number and size of intramyocellular lipid droplets is increased in the presence of cancer and increases further with weight loss/loss of adipose mass in other body compartments.