Pro-inflammatory cytokine alterations in recent onset anorexia nervosa adolescent female patients before and after 6 months of integrated therapy: A case-control study.

Anorexia nervosa (AN) is a complex disorder affecting mainly, but not only, teenagers. Researchers agree that AN is deeply associated with a pro-inflammatory state following an impaired immune system, resulting from altered levels of cytokines such as IL-1ß and TNF-α, also impacted by the frequent depressive states. Thus, this case-control study aimed to evaluate the relationship between patients suffering from AN undergoing specialized eating disorder treatment for AN and pro-inflammatory cytokines. To reach our purpose, we assessed eating-related psychopathology and depressive symptoms and measured serum concentration of pro-inflammatory cytokines IL-1ß, IL-6, IL-8, and TNF-α before and after 6 months of integrated therapy (which included psychopharmacotherapy, psychotherapy, and nutritional treatment), to define whether selected pro-inflammatory cytokines could be considered a pathophysiological marker of the disorder. A sample of 16 young female patients with early diagnosis of AN, and without any previous treatment, and 22 healthy controls matched by age, sex, and socioeconomic status were enrolled. After 6 months of integrated therapy, a significant decrease of all selected pro-inflammatory cytokines was detected. In addition, an improvement in the anxiety-depressant aspects was also noted. In conclusion, the results obtained suggest that pro-inflammatory cytokines are indeed related to the pathophysiology of AN. However, further investigations, involving larger samples of patients with distinct subtypes of AN, are essential to confirm the current findings.

"I see it very much as an end-of-life food" - Barriers to oral nutritional supplement adherence, views from healthy older adults.

Malnutrition affects approximately one quarter of UK adults aged 65 years and over. As the global demographic shift continues, malnutrition is expected to increase. Oral nutritional supplements (ONS) are used both to prevent and to treat malnutrition. However, their effectiveness is compromised by poor adherence, and it is not well understood what contributes to this. Therefore, the current research was designed to explore ONS adherence from the parallel perspectives of ONS as a prescribed "medication" and as a food supplement/substitute. Eighteen older adults (13F, 5M; mean age = 73.4 yr; range: 70-80 yr) participated in focus groups (three in-person and one online), to investigate experiences of taking prescribed medications, including dietary supplements, and what should be factors to consider in supporting regular intake of ONS for trial development, as well as any potential improvements to products. Focus group sessions were recorded and then transcribed. Thematic Analysis was applied to the transcripts by the first author, and themes were discussed in depth, using exemplar quotes from participants. Five dominant themes were identified from the data: Disgust, Palatability and Acceptance; End-of-Life Care; Resistance to Medicines; Rituals and Reminders; and Real Food Displacement. Nutritional supplements were characterised as "disgusting", "manufactured", and associated with serious, chronic illness, as well as end-of-life care, in contrast to probiotics which were linked with health and wellness. The sweet taste of ONS was identified as a barrier to intake, given that it is generally associated with a signal to stop eating, and low hunger. As a group, participants tried to "avoid taking medicines", and viewed the need to have them negatively, yet most regularly took prescribed medication and/or vitamin supplements. Participants identified several, rituals and reminders to take medicines, including meal-based, or time-of-day-based prompts (e.g., before, with or after meals). To improve adherence, savoury products were suggested, as well as a more person-centred approach to individual nutritional needs and preferences. Overall, the group discussion mainly identified barriers to intake, but that improving taste, adding to "real food" (not replacing meals), and offering variety of flavour and form (e.g., savoury soups as well as sweet drinks) could be included in future trials to improve appeal and therefore intake. Future work should continue to explore how best to formulate, market and/or prescribe ONS, and how this might vary for malnutrition prevention vs treatment strategies.

Choosing Appropriate Nutritional Therapy for Patients With Anorexia Nervosa Exhibiting Liver Dysfunction: A Case Report.

Anorexia nervosa (AN) presents with a variety of physical complications such as hypoglycemia, electrolyte abnormalities, and dehydration associated with starvation, requiring rapid weight gain through nutritional therapy. However, despite nutritional therapy, patients are at risk of many serious medical complications, including hypoglycemia, hypophosphatemia, edema, and liver damage. Starvation has been found to cause hepatocyte injury with mild-to-severe increases in liver enzyme levels, and distinguishing between autophagy and refeeding syndrome is important for treatment strategies. Herein, we report a rare case of sudden liver injury after the initiation of nutritional therapy in a patient with AN. A 35-year-old woman was admitted to our hospital for the treatment of weight loss due to AN. Nutritional therapy was initiated at 600 kcal/day and increased to 1500 kcal/day on the 21st day of admission. On the 22nd day after admission, rapid liver injury was observed, with an aspartate aminotransferase level of 141 U/L and an alanine aminotransferase level of 221 U/L. After the exclusion of refeeding syndrome, since there was no evidence of hypokalemia, hypophosphatemia, or fatty liver disease based on blood tests and abdominal echography, we diagnosed starvation-induced hepatocyte autophagy, and she was treated with the same calories. Her liver dysfunction gradually improved thereafter. This case report highlights the clinical utility of identifying the etiology of hepatic dysfunction in patients with AN. Clinicians must make appropriate decisions regarding continuing or reducing nutritional therapy based on relevant tests when patients with AN develop liver dysfunction after the initiation of nutritional therapy.

Clinical effectiveness, cost-effectiveness and process evaluation of group schema therapy for eating disorders: study protocol for a multicenter randomized controlled trial.

BACKGROUND: Eating disorders (EDs), such as (atypical) Anorexia (AN) and Bulimia Nervosa (BN), are difficult to treat, causing socioeconomic impediments. Although enhanced cognitive behavioral therapy (CBT-E) is widely considered clinically effective, it may not be the most beneficial treatment for (atypical) AN and BN patients who do not show a rapid response after the first 4 weeks (8 sessions) of a CBT-E treatment. Alternatively, group schema therapy (GST) may be a valuable treatment for this ED population. Even though GST for EDs has yielded promising preliminary findings, the current body of evidence requires expansion. On top of that, data on cost-effectiveness is lacking. In light of these gaps, we aim to describe a protocol to examine whether GST is more (1) clinically effective and (2) cost-effective than CBT-E for (atypical) AN and BN patients, who do not show a rapid response after the first 4 weeks of treatment. Additionally, we will conduct (3) process evaluations for both treatments. METHODS: Using a multicenter RCT design, 232 Dutch (atypical) AN and BN patients with a CBT-E referral will be recruited from five treatment centers. Clinical effectiveness and cost-effectiveness will be measured before treatment, directly after treatment, at 6 and at 12 months follow-up. In order to rate process evaluation, patient experiences and the degree to which treatments are implemented according to protocol will be measured. In order to assess the quality of life and the achievement of personalized goals, interviews will be conducted at the end of treatment. Data will be analyzed, using a regression-based approach to mixed modelling, multivariate sensitivity analyses and coding trees for qualitative data. We hypothesize GST to be superior to CBT-E in terms of clinical effectiveness and cost-effectiveness for patients who do not show a rapid response to the first 4 weeks of a CBT-E treatment. DISCUSSION: To our knowledge, this is the first study protocol describing a multicenter RCT to explore the three aforementioned objectives. Related risks in performing the study protocol have been outlined. The expected findings may serve as a guide for healthcare stakeholders to optimize ED care trajectories. TRIAL REGISTRATION: clinicaltrials.gov (NCT05812950).

Influence of the gut microbiome on appetite-regulating neuropeptides in the hypothalamus: Insight from conventional, antibiotic-treated, and germ-free mouse models of anorexia nervosa.

Recent research highlights the profound impact of the gut microbiome on neuropsychiatric disorders, shedding light on its potential role in shaping human behavior. In this study, we investigate the role of the gut microbiome in appetite regulation using activity-based anorexia (ABA) mouse model of anorexia nervosa (AN) - a severe eating disorder with significant health consequences. ABA was induced in conventional, antibiotic-treated, and germ-free mice. Our results show the clear influence of the gut microbiome on the expression of four orexigenic (neuropeptide Y, agouti-related peptide, melanin-concentrating hormone, and orexin) and four anorexigenic peptides (cocaine- and amphetamine-regulated transcript, corticotropin-releasing hormone, thyrotropin-releasing hormone, and pro-opiomelanocortin) in the hypothalamus. Additionally, we assessed alterations in gut barrier permeability. While variations were noted in germ-free mice based on feeding and activity, they were not directly attributable to the gut microbiome. This research emphasizes that the gut microbiome is a pivotal factor in AN's appetite regulation beyond just dietary habits or physical activity.

Refeeding syndrome and psychopharmacological interventions in children and adolescents with Anorexia Nervosa: a focus on olanzapine-related modifications of electrolyte balance.

This study aims to investigate the potential correlation between the use of olanzapine, a psychopharmacological intervention commonly prescribed in Anorexia Nervosa treatment, and the occurrence of Refeeding Syndrome. Despite the acknowledged nutritional and biochemical impacts of olanzapine, the literature lacks information regarding its specific association with Refeeding Syndrome onset in individuals with Anorexia Nervosa. This is a naturalistic, retrospective, observational study, reporting the occurrence of Refeeding Syndrome in children and adolescents with Anorexia Nervosa, treated or untreated with olanzapine. Dosages and serum levels of olanzapine were assessed for potential associations with the occurrence of Refeeding Syndrome and specific variations in Refeeding Syndrome-related electrolytes. Overall, 113 patients were enrolled, including 46 (41%) who developed a Refeeding Syndrome. Mild (87%), moderate (6.5%), and severe (6.5%) Refeeding Syndrome was described, at a current average intake of 1378 ± 289 kcal/day (39 ± 7.7 kcal/kg/die), frequently associated with nasogastric tube (39%) or parenteral (2.2%) nutrition. Individuals receiving olanzapine experienced a more positive phosphorus balance than those who did not (F(1,110) = 4.835, p = 0.030), but no difference in the occurrence of Refeeding Syndrome was documented. The mean prescribed doses and serum concentrations of olanzapine were comparable between Refeeding Syndrome and no-Refeeding Syndrome patients.    Conclusion: The present paper describes the occurrence of Refeeding Syndrome and its association with olanzapine prescriptions in children and adolescents with Anorexia Nervosa. Olanzapine was associated with a more positive phosphorus balance, but not with a different occurrence of Refeeding Syndrome. Further, longitudinal studies are required. What is Known: • Refeeding Syndrome (RS) is a critical complication during refeeding in malnourished patients, marked by electrolyte (phosphorus, magnesium, potassium) imbalances. • Olanzapine, an atypical antipsychotic with nutritional and biochemical impacts, is used in Anorexia Nervosa (AN) treatment, however data concerning its association with RS are lacking. What is New: • The study observed RS in 46/113 (41%) young patients with AN. • Olanzapine-treated individuals showed a higher improvement in serum phosphate levels than untreated ones, although no impact on the occurrence of Refeeding Syndrome was observed.

Is there a basis for a weight cut-off point? A large-scale investigation of atypical anorexia and anorexia nervosa subtypes among patients at a residential treatment centre.

OBJECTIVE: There is debate surrounding how to differentiate between anorexia nervosa (AN) and atypical AN (atypAN) as diagnostic entities, and whether a distinction based on BMI is warranted. Better understanding eating disorder (ED) and emotional symptoms across atypAN and AN subtypes [AN-restricting (AN-R), AN-binge/purge (AN-BP)], with and without controlling for BMI, can elucidate how atypAN differs from AN subtypes and whether there is a basis for a BMI cut-off. METHODS: 1810 female patients at an ED treatment centre completed intake surveys. ANCOVAs assessed differences across AN-R (n = 853), AN-BP (n = 726), and atypAN (n = 231) groups on ED, depressive, and anxiety symptoms, anxiety sensitivity, experiential avoidance, and mindfulness, with and without controlling for BMI. RESULTS: Relative to AN-R, atypAN and AN-BP groups endorsed significantly higher ED and depressive symptoms, anxiety sensitivity, experiential avoidance, and significantly lower mindfulness (all p < 0.001), but atypAN and AN-BP groups did not differ from one another. When controlling for BMI, all previously significant differences between atypAN and AN-R did not remain significant. CONCLUSION: Individuals with atypAN who have a higher BMI experience more pronounced ED and emotional symptoms, suggesting that relying solely on BMI as a marker of illness severity may be problematic.

Hypothalamic subregion alterations in anorexia nervosa and obesity: Association with appetite-regulating hormone levels.

OBJECTIVE: Anorexia nervosa (AN) and obesity are weight-related disorders with imbalances in energy homeostasis that may be due to hormonal dysregulation. Given the importance of the hypothalamus in hormonal regulation, we aimed to identify morphometric alterations to hypothalamic subregions linked to these conditions and their connection to appetite-regulating hormones. METHODS: Structural magnetic resonance imaging (MRI) was obtained from 78 patients with AN, 27 individuals with obesity and 100 normal-weight healthy controls. Leptin, ghrelin, and insulin blood levels were measured in a subsample of each group. An automated segmentation method was used to segment the hypothalamus and its subregions. Volumes of the hypothalamus and its subregions were compared between groups, and correlational analysis was employed to assess the relationship between morphometric measurements and appetite-regulating hormone levels. RESULTS: While accounting for total brain volume, patients with AN displayed a smaller volume in the inferior-tubular subregion (ITS). Conversely, obesity was associated with a larger volume in the anterior-superior, ITS, posterior subregions (PS), and entire hypothalamus. There were no significant volumetric differences between AN subtypes. Leptin correlated positively with PS volume, whereas ghrelin correlated negatively with the whole hypothalamus volume in the entire cohort. However, appetite-regulating hormone levels did not mediate the effects of body mass index on volumetric measures. CONCLUSION: Our results indicate the importance of regional structural hypothalamic alterations in AN and obesity, extending beyond global changes to brain volume. Furthermore, these alterations may be linked to changes in hormonal appetite regulation. However, given the small sample size in our correlation analysis, further analyses in a larger sample size are warranted. PUBLIC SIGNIFICANCE: Using an automated segmentation method to investigate morphometric alterations of hypothalamic subregions in AN and obesity, this study provides valuable insights into the complex interplay between hypothalamic alterations, hormonal appetite regulation, and body weight, highlighting the need for further research to uncover underlying mechanisms.

The role of mindfulness on the psychological aspects of anorexia nervosa.

OBJECTIVE: Emotion regulation, perfectionism, and rumination are perpetuating factors in anorexia nervosa (AN). Mindfulness can be protective and therapeutic. We aimed to understand the relationship between these factors and mindfulness in AN. METHODS: 20 adolescent girls in the acute phase of the AN, 16 in remission, and 40 in the control group were evaluated. RESULTS: Mindfulness was lowest in the acute AN group. The difference in the acute AN group regarding body dissatisfaction, emotion dysregulation, perfectionism, and mindfulness disappeared after controlling for the effects of depression and anxiety. The predictors of disordered eating in the entire study population were body dissatisfaction and depressive symptoms. Emotion regulation and perfectionism were the predictors of mindfulness in the acute AN group and the entire study population. When mindfulness decreased, concerns about body shape increased in both acute AN and remission groups, while dietary restriction and disordered eating behaviors increased only in the remission group. DISCUSSION: Emotion regulation difficulties in acute AN could be related to depression and anxiety. Mindfulness interventions for emotion regulation could be used for depression during the acute phase while for perfectionism in remission. Early intervention for depression and body dissatisfaction seems protective, and mindfulness could be an appropriate intervention.

Eye movement desensitisation and reprocessing as add-on treatment to enhanced cognitive behaviour therapy for patients with anorexia nervosa reporting childhood maltreatment: A quasi-experimental multicenter study.

OBJECTIVE: This quasi-experimental study aimed to compare the outcome of patients with Anorexia Nervosa (AN) reporting moderate/severe childhood maltreatment (CM) treated exclusively with Enhanced Cognitive Behaviour Therapy (CBT-E) or with CBT-E plus Eye Movement Desensitisation and Reprocessing (EMDR). METHOD: A total of 75 patients with AN reporting moderate/severe CM were initially assessed regarding body mass index (BMI), general and eating disorder (ED)-specific psychopathology, and dissociative symptoms, and re-evaluated after 40 CBT-E sessions (T1). Then, 18 patients received EMDR, whereas the others were placed on a waiting list and continued CBT-E. T2 assessment was performed after 20-25 sessions of EMDR or CBT-E. A control group of 67 patients without CM was also enroled and treated with CBT-E. RESULTS: Contrary to patients without CM, neither of the traumatised groups improved in BMI, general and ED psychopathology, or dissociation at T1. However, at T2, both traumatised groups improved in BMI and ED-specific psychopathology, with the CBT + EMDR group demonstrating greater improvements. Moreover, only the CBT + EMDR group improved in general psychopathology and dissociative symptoms. The reduction of ED symptoms in traumatised patients was mediated by the amelioration of dissociation. DISCUSSION: The addition of EMDR to CBT-E may benefit patients with AN reporting moderate/severe CM.

Orexin-A attenuated motion sickness through modulating neural activity in hypothalamus nuclei.

BACKGROUND AND PURPOSE: We evaluated the hypothesis that central orexin application could counteract motion sickness responses through regulating neural activity in target brain areas. EXPERIMENTAL APPROACH: Thec effects of intracerebroventricular (i.c.v.) injection of orexin-A and SB-334867 (OX1 antagonist) on motion sickness-induced anorexia, nausea-like behaviour (conditioned gaping), hypoactivity and hypothermia were investigated in rats subjected to Ferris wheel-like rotation. Orexin-A responsive brain areas were identified using Fos immunolabelling and were verified via motion sickness responses after intranucleus injection of orexin-A, SB-334867 and TCS-OX2-29 (OX2 antagonist). The efficacy of intranasal application of orexin-A versus scopolamine on motion sickness symptoms in cats was also investigated. KEY RESULTS: Orexin-A (i.c.v.) dose-dependently attenuated motion sickness-related behavioural responses and hypothermia. Fos expression was inhibited in the ventral part of the dorsomedial hypothalamus (DMV) and the paraventricular nucleus (PVN), but was enhanced in the ventral part of the premammillary nucleus ventral part (PMV) by orexin-A (20 µg) in rotated animals. Motion sickness responses were differentially inhibited by orexin-A injection into the DMV (anorexia and hypoactivity), the PVN (conditioned gaping) and the PMV (hypothermia). SB-334867 and TCS-OX2-29 (i.c.v. and intranucleus injection) inhibited behavioural and thermal effects of orexin-A. Orexin-A (60 µg·kg-1) and scopolamine inhibited rotation-induced emesis and non-retching/vomiting symptoms, while orexin-A also attenuated anorexia with mild salivation in motion sickness cats. CONCLUSION AND IMPLICATIONS: Orexin-A might relieve motion sickness through acting on OX1 and OX2 receptors in various hypothalamus nuclei. Intranasal orexin-A could be a potential strategy against motion sickness.

[Anorexia nervosa and music therapy]. / Anorexie mentale et musicothérapie.

Supporting people suffering from anorexia nervosa remains a challenge. While traditional treatment focuses more on speech and its emergence for the patient and family, non-medicinal and non-verbal therapies are used more systematically, sometimes as a last resort. Yet, as a non-verbal mediated therapy, music therapy can find a legitimate place and complement all the psychiatric, psychotherapeutic, somatic, dietetic and nursing areas where speech already circulates.

Renal failure following insulin purging in atypical anorexia nervosa and type 1 diabetes mellitus.

Objective: Anorexia nervosa (AN) and atypical anorexia nervosa (AAN) are severe and complex eating disorders that can be prevalent among individuals with type 1 diabetes mellitus (T1DM). Insulin purging, characterized by the intentional underuse / omission of insulin to control weight, is under-recognized in medicine and is a purging strategy of patients with AN or AAN and comorbid T1DM. Often, this can lead to renal failure, necessitating a (pancreas-) kidney transplantation. This article presents a comprehensive overview of the interplay between AN/AAN and T1DM and summarizes the evidence in literature. Methods: A narrative review is presented on basis of a detailed case study of a 32-year-old female with end-stage renal failure seeking (pancreas-) kidney transplantation displaying etiology, diagnosis, comorbidities, complications, and treatment of AN and AAN with emphasis on those patients with T1DM. Results: Insulin purging in patients with AN/AAN and coexisting T1DM can exacerbate T1DM complications, including accelerating the onset of end-stage renal failure. A multidisciplinary approach including nutrition treatment and psychotherapeutic techniques was considered necessary for treatment, focusing on psychosomatic in-patient care before and after organ transplantation. Conclusion: Insulin purging in patients with AAN and T1DM poses severe health risks, including accelerated renal complications. For those considering transplantation, insulin purging has explicitly to be diagnosed and a holistic treatment addressing both the renal condition and psychosomatic symptoms/disorders is crucial for successful post-transplant outcomes.

[Healing the mind by healing the body in anorexia nervosa]. / Soigner le mental en soignant le corps dans l'anorexie mentale.

In anorexia nervosa, physical and psychological vulnerability confines the sufferer to the confines of his or her pathology. The physical body is the first victim of undernutrition, but also the first resource for restoring the psychic and emotional body. Reduced food intake has repercussions on cognition and affect, all of which affect relational capacities. Accompanying, understanding and caring for people means reaching out to them and their bodies, to re-establish the link between what has been broken, and to establish a relationship of trust with them.

A case report of anorexia nervosa in a 23-year-old Ethiopian woman.

Key Clinical Messages: Limited studies on AN in Africa, including Ethiopia. Internet and media have changed body image portrayal in developing countries. A need for a multidisciplinary approach to treatment, training on positive coaching styles, and future research. Abstract: The Global Burden of Disease had estimated anorexia nervosa (AN) or bulimia nervosa to be 13.6 million people. The lifetime prevalence of AN ranges from 2.4 to 4.3 percent. During their lifetime, up to 4% of females and up to 0.3% of males suffer from anorexia nervosa. Studies assessing AN in Africa, including Ethiopia, are limited. This case report describes a 23-year-old female patient who presented with anorectic symptoms and signs in Ethiopia. This case report describes a 23-year-old female patient who participated in sports activities. She had a low body weight based on a BMI of 13.15 kg/m2 and lost around 10 kg within the past 6 months. She feared gaining weight or becoming fat, thus restricting food intake. The findings on psychiatric evaluation encompassing detailed history and mental state examination suggested the diagnosis of Extreme anorexia nervosa, restricting type; adult malnutrition; major depressive disorder (MDD) (in remission); low risk of aggression; low risk of suicide; severe functional impairment. The general management principles implemented in this patient included assessment of medical complications, weight restoration, psychological intervention, medication for comorbid depression, and long-term psychological and biological treatment follow-up to avoid relapse. The presented case of a 23-year-old Ethiopian female patient who is athletic shows weight-controlled sports activities and the manifestation of anorexia nervosa. Easy access to the Internet and media has changed body image portrayal in developing countries including Ethiopia. There is a need for a multidisciplinary approach involving psychiatrists, psychologists, internists, and nutritionists for the management of AN. The early screening and management of medical complications are crucial. There is a need for close monitoring of vital signs, restriction of caffeine, excess fluid, and salt, and limiting excessive exercise. Furthermore, to assess micronutrient deficiencies, vitamin supplements should be prescribed in the form of multivitamin and thiamine preparations. The need for future training about positive coaching styles for coaches is mandatory to reduce the future impacts on young athletes. There is a need for future research on eating disorders in developing countries such as Ethiopia.

Acute liver failure and aplastic crisis due to anorexia nervosa in an adolescent girl: a case report.

Anorexia nervosa (AN) has a high mortality rate due to the widespread organ dysfunction caused by the underlying severe malnutrition. Malnutrition-induced hepatitis is common among individuals with AN especially as body mass index decreases, while acute liver failure and aplastic crisis related to coagulation disease and encephalopathy rarely occur in AN patients. The supervised increase of caloric intake can quickly improve the elevated aminotransferases caused by starvation and aplastic crisis. This current case report describes a 12-year-old adolescent girl who was admitted with a 3-month history of weight loss. Within 3 months, she had lost 10 kg of weight. The girl was diagnosed with AN, acute liver failure, severe malnutrition with emaciation, electrolyte disorder, bradycardia and aplastic crisis. She was gradually supplemented with vitamins and enteral nutrition to avoid refeeding syndrome. After treatment, her liver function and haematopoietic function returned to normal. In conclusion, acute liver failure and aplastic crisis are rare but potentially life-threatening complications of AN, which could be improved by supervised feeding and timely rehydration. AN should be considered as the potential aetiology of acute liver failure and aplastic crisis.

Comparison between continued inpatient treatment versus day patient treatment after short inpatient care in early onset anorexia nervosa (COTIDEA trial): a study protocol for a non-inferiority randomised controlled trial.

BACKGROUND: In children with early-onset anorexia nervosa (first symptoms before 13 years old, EO-AN), experts recommend initial outpatient treatment but in-patient treatment (IP) is frequently indicated due to acute medical instability or for those who have not improved with outpatient treatment. This IP can target either a partial weight restauration or a total weight normalization (return to the previous BMI growth trajectory). There are no evidence in the literature on which is the better therapeutic option in EOAN. But as long length of stay induce social isolation, with elevated costs, we wonder if a stepped-care model of daypatient treatment (DP) after short IP stabilisation may be a treatment option as effective as full-time IP to target weight normalization. We designed a two-arm randomised controlled trial testing the non-inferiority of a stepped-care model of DP after short IP stabilisation versus full-time IP. METHODS: Eighty-eight children aged 8 to 13 years suffering from EOAN with initial severe undernutrition will be randomly allocated to either IP treatment as usual or a stepped care DP model both targeting weight normalization. Assessments will be conducted at inclusion, somatic stabilization, weight normalization, 6 months and 12 months post randomisation. The primary outcome will be BMI at 12 months post-randomisation. Secondaries outcomes will included clinical (tanner stage), biological (prealbumin, leptin, total ghrelin and IGF1) and radiological (bone mineralization and maturation) outcomes, eating symptomatology and psychiatric assessments, motivation to change, treatment acceptability and quality of life assessments, cost-utility and cost-effectiveness analyses. DISCUSSION: COTIDEA will provide rigorous evaluation of treatment alternative to full-time inpatient treatment to allow a reduction of social iatrogenic link to hospital length of stay and associated costs. TRIAL REGISTRATION: Trial is registered on ClinicalTrials.gov (NCT04479683).

Improvement in Tubulointerstitial Nephritis With Glucocorticoid Therapy in an Anorexia Nervosa Patient.

Anorexia nervosa is a psychiatric disorder that is often diagnosed in adolescents and young adults. Renal-related complications of anorexia nervosa include abnormal water metabolism, electrolyte abnormalities, and nephrocalcinosis, which may lead to irreversible renal damage. Furthermore, tubulointerstitial nephritis has been reported as a renal pathological feature of anorexia nervosa. Immunosuppressive therapy, such as with glucocorticoids, has been recommended for idiopathic interstitial nephritis treatment; however, the effectiveness of immunosuppressive therapy for interstitial nephritis in patients with anorexia nervosa remains unestablished. Here, we report a case of interstitial nephritis in a patient with anorexia nervosa whose renal function was successfully improved with glucocorticoid therapy. The patient was a 38-year-old woman who was referred for renal dysfunction (estimated glomerular filtration rate: 7.6 mL/min/1.73 m2). She had anorexia nervosa and repeated episodes of vomiting. Hypokalemia (K: 2.1 mEq/L) and metabolic alkalosis (HCO3-: 54.2 mEq/L) were observed. Fluid therapy and potassium supplementation did not improve renal function; therefore, a percutaneous renal biopsy was performed. The renal pathology results revealed interstitial fibrosis, inflammatory cell infiltration in the interstitium, and tubulitis, suggesting a diagnosis of tubulointerstitial nephritis. Glucocorticoid therapy improved the patient's renal function to an estimated glomerular filtration rate of 19.91 mL/min/1.73 m2, and the renal function remained stable thereafter. This case suggests that glucocorticoid therapy may be considered for the treatment of interstitial nephritis in patients with anorexia.

Acupuncture at Sifeng (EX-UE 10) for pediatric anorexia: A systematic review and meta-analysis.

OBJECTIVE: The purpose of this study was to assess the efficacy and safety of acupuncture at Sifeng for pediatric anorexia. METHODS: The randomized controlled trials (RCTs) of acupuncture at Sifeng for pediatric anorexia from their beginning to October 2022 were looked up in the seven databases. The Cochrane risk of bias evaluation tool was applied to the risk of bias analysis of the included studies. A meta-analysis of the total efficiency, score of food intake reduction, time to normalize food intake, body weight, leptin levels, and blood zinc levels was performed using Review Manager 5.3 software. The GRADE criteria were applied to assess the evidence's quality. RESULTS: A total of 24 RCTs were included, involving 2202 children. The allocation of concealment, blinding, and selective reporting has a high or unclear risk of bias. All experiments compared acupuncture at Sifeng with traditional Chinese medicine or Western medicine. The results showed that, compared with medicine, acupuncture at Sifeng could significantly improve the total efficiency (OR=6.44, 95%CI [4.78,8.66]), lower the score of food intake reduction (MD=-0.69, 95%CI [-1.00, -0.39]), decrease leptin levels (MD=-5.19, 95%CI [-8.09, -2.29]) and time to normal food intake (MD=-2.22, 95%CI [-2.42, -2.01]), increase blood zinc (MD=0.79, 95%CI [0.21, 1.37]) and body weight (MD=1.28, 95%CI [0.85, 1.72]). Seven studies found that the treatment was safe both during and after. Based on the GRADE criteria, the quality of the evidence for the majority of indicators was extremely poor. CONCLUSION: The low certainty of evidence suggested that acupuncture at Sifeng was effective and safe in the therapy of pediatric anorexia. Future high-quality clinical studies are needed to provide more reliable evidence of the effectiveness and safety of the therapy.

Hypothalamic volume is associated with body mass index.

The hypothalamus is an important neuroendocrine hub for the control of appetite and satiety. In animal studies it has been established that hypothalamic lesioning or stimulation causes alteration to feeding behaviour and consequently body mass, and exposure to high calorie diets induces hypothalamic inflammation. These findings suggest that alterations in hypothalamic structure and function are both a cause and a consequence of changes to food intake. However, there is limited in vivo human data relating the hypothalamus to obesity or eating disorders, in part due to technical problems relating to its small size. Here, we used a novel automated segmentation algorithm to exploratorily investigate the relationship between hypothalamic volume, normalised to intracranial volume, and body mass index (BMI). The analysis was applied across four independent datasets comprising of young adults (total n = 1,351 participants) spanning a range of BMIs (13.3 - 47.8 kg/m2). We compared underweight (including individuals with anorexia nervosa), healthy weight, overweight and obese individuals in a series of complementary analyses. We report that overall hypothalamic volume is significantly larger in overweight and obese groups of young adults. This was also observed for a number of hypothalamic sub-regions. In the largest dataset (the HCP-Young Adult dataset (n = 1111)) there was a significant relationship between hypothalamic volume and BMI. We suggest that our findings of a positive relationship between hypothalamic volume and BMI is potentially consistent with hypothalamic inflammation as seen in animal models in response to high fat diet, although more research is needed to establish a causal relationship. Overall, we present novel, in vivo findings that link elevated BMI to altered hypothalamic structure. This has important implications for study of the neural mechanisms of obesity in humans.