Ulrich Cuntz

Background: Laboratory parameters and body weight are objective markers of physical stability in patients with severe and extreme anorexia nervosa. However, systematic analyses of trajectories during inpatient treatment with high-calorie refeeding and prophylactic phosphate supplementation remain limited in extremely underweight persons. Therefore, it is essential to gain a comprehensive understanding of changes in laboratory parameters, body mass index, and factors influencing these trajectories under this treatment approach in patients with severe and extreme anorexia nervosa, who are at particularly high risk of medical complications. Methods: Retrospective data of a six-week treatment period from 519 female inpatients of a specialized care unit with anorexia nervosa (body mass index at admission: M = 12.6 kg/m ² , SD = 1.35) were analyzed. Laboratory parameters (hemoglobin, thrombocytes, leukocytes, aspartate aminotransferase, alanine aminotransferase, creatine kinase, sodium, potassium, and phosphate) and body weight were assessed weekly. Results: More than one-third of patients showed leukopenia or hypertransaminasemia at admission. Most laboratory values and body mass index tended to ameliorate during the six-week treatment period. Lower body mass index at admission or longer illness duration was associated with larger changes in body mass index and several laboratory parameters (e.g., hemoglobin or aspartate aminotransferase). Conclusions: These findings provide a detailed characterization of laboratory changes during inpatient refeeding with prophylactic phosphate supplementation. The observed temporal patterns of laboratory stabilization may help inform individualized monitoring strategies and provide a basis for evaluating whether the frequency of routine laboratory testing can be tailored over a longer course of treatment according to clinical status and resolution of previous abnormalities. Furthermore, these findings may support the effectiveness and safety of inpatient refeeding protocols with prophylactic phosphate supplementation in patients with severe and extreme anorexia nervosa and an extremely low body mass index at admission (< 13 kg/m ² ).

Objective: While high caloric realimentation (HCR) is increasingly recommended for quick weight restoration of patients with anorexia nervosa (AN), the development of AN‐specific psychopathology and somatic symptoms during HCR have so far insufficiently been studied. Method: Patients hospitalised for the treatment of AN received oral realimentation starting with 2000 kcal under close medical monitoring and a substitution regimen. Weekly over the initial 6 weeks of treatment, assessments included body weight, drive for thinnesss, body dissatisfaction, depression, and somatic symptoms. Results: In 46 patients (mean age 27.57 years, 2 males, 44 females), the body mass index increased from 12.6 (SD 1.1) at baseline to 14.4 (SD 1.0) kg/m ² ( p < 0.001) at week 6 ( d = 2.57). Drive for thinnesss did not change (28.9 [SD 10.2] to 27.7 [SD 10.8]; p = 0.102), while body dissatisfaction increased slightly from 37.3 (SD 7.8) to 39.1 (SD 9.2; p = 0.019; d = 0.41). Depression and somatic symptoms decreased significantly ( p < 0.001) with large effect sizes ( d = 1.09, d = 0.90, respectively). No case of refeeding syndrome was encountered. Discussion: HCR was medically safe and associated with a decrease in depressive and somatic symptoms at only slight increase in body dissatisfaction. Fast realimentation brings patients with extreme AN quickly out of a weight range dangerous to their health.

Background: Inpatient treatment successfully increases body weight and decreases eating disorder and associated symptoms in patients with anorexia nervosa (AN). However, relapse rates are high, particularly within the first year after discharge. Methods: We examined treatment outcome one year after discharge in adults with AN (N = 80, 2 males; BMI at admission: M = 13.2 kg/m², SD = 1.79) who received treatment in a specialized inpatient unit for AN patients with severe underweight (body mass index < 15 kg/m²) and/or excessive purging or exercising. Results: From admission to discharge, body weight and self-reported life satisfaction significantly increased and self-reported eating disorder symptoms, depressive symptoms, and compulsive exercise significantly decreased. From discharge to follow up, life satisfaction and body weight decreased, and eating disorder symptoms, depressive symptoms, and compulsive exercise increased, although 87% of patients indicated to have received some kind of eating disorder treatment in the past six months. At follow up, the majority of patients indicated that they regularly ate three meals per day in the past week, including consumption of high-calorie, formerly forbidden foods. However, only a minority of patients indicated that they adhered to the hospital’s guidelines on portion sizes. Patients’ self-reported desired body weight at follow up was significantly higher than their current body weight. Conclusions: While inpatient treatment results in substantial improvements that are partially maintained after discharge, severe and extreme cases of AN require more long-lasting, alternating treatment approaches (e.g., interval treatment) to ensure long-term recovery.

The microbiota–gut–brain axis may play a role in the pathophysiology of anorexia nervosa (AN). Here, the relationship between the gastrointestinal microbiota and symptoms of depression, anxiety, and eating disorder pathology in patients with AN before (n = 55) and after weight restoration (n = 44) was investigated by reanalyzing the data of the MICROBIAN study. The gastrointestinal microbiota was analyzed using 16S rRNA amplicon sequencing. Symptoms of anxiety disorder, depression, and the severity of the eating disorder were measured by validated questionnaires. All analyses were adjusted for the body mass index (BMI). Several significant findings between psychological parameters and the gastrointestinal microbiota were not evident after controlling for the BMI. No differences in alpha and beta diversity between groups of higher and lower symptom severity levels for depression and anxiety were found. Positive associations between species of Blautia and Ruminococcus and depression symptoms, and between the phylum Firmicutes and anxiety symptoms were observed after rehabilitation, respectively. A positive correlation was found between propionate and acetate levels and the reduction of depression severity during inpatient treatment. Accounting for the weight status when analyzing the relationship between psychological parameters and the gastrointestinal microbiota in patients with underweight is important since the BMI may be the driver for many observed changes.

Anorexia nervosa is associated with a significant risk of morbidity and mortality. In clinical practice, health risk is assessed and estimated using routinely collected laboratory data. This study will develop a risk score using clinically relevant laboratory parameters. The related question is how to estimate the health risk associated with underweight using body weight, height and age. Methods: We used routinely collected laboratory parameters from a total of 4087 patients. The risk score was calculated on the basis of electrolytes, blood count, transaminases and LDH. The nine parameters used were summed as zlog-transformed values. Where appropriate, the scales were inverted so that high values represented higher risk. For statistical prediction of the risk score, weight/height and age reference values from the WHO, the CDC (Center of Disease Control) and representative studies of German children and adults (KIGGS and NNS) were used. Results: The score calculated from nine laboratory parameters already shows a convincing relationship with BMI. Among the weight measures used for height and age, the z-score from the CDC reference population emerged as the best estimate, explaining 34% of the variance in health risk measured by the laboratory score. The percentile rank for each age-specific median weight from the KIGGS/NNS still explained more than 31% of the variance. In contrast, percentiles explained less variance than BMI without age correction. Conclusions: The score we used from routine laboratory parameters appears to be an appropriate measure for assessing the health risk associated with underweight, as measured by the quality of the association with BMI. For estimating health risk based on weight, height and age alone, z-scores and percentages of age-specific median weight, as opposed to percentiles, are appropriate parameters. However, the study also shows that existing age-specific BMI reference values do not represent risk optimally. Improved statistical estimation methods would be desirable.

Background: The present study investigates the relationship between hypertransaminasemia and malnutrition on the basis of a very large number of patients. We assume that the level of transaminases not only reflects the extent of underlying liver cell damage but also provides information about the metabolic situation under conditions of energy deficiency. Methods: We present an observational study in two different samples. The first sample consists of 3755 patients (mean age 22.7 years, Range 12–73 years; mean BMI 15.4 kg/m², range 8.1–25.7) out of a total of 4212 patients with anorexia nervosa treated in the Roseneck Clinic within five years for whom a complete admission laboratory was available. The second sample was obtained from a special ward for medically at-risk patients with eating disorders. During the period in question, four hundred and ten patients with anorexia nervosa were treated. One hundred and forty-two female patients (mean age 26.4 years, Range 18–63 years; mean BMI 11.5 kg/m², range 8.4–13) had a BMI of thirteen or less and a complete data set was obtained at admission and weekly in the following four weeks after admission. Results: The increase in liver transaminases shows a very high correlation with weight in sample one (N = 3755). The analysis of variance shows highly significant (p < 0.001) and GPT/ALT from 88 to 41 U/L (F = 9.9, p < 0.001) within four weeks. Discussion: Below a BMI of about 13, the nutritional status of the patients becomes so critical that the energy supply of the patient is increasingly dependent on the autophagy of the liver, which can be seen in the very strong increase in transaminases here. Refeeding leads very quickly to the normalisation of the transaminases and, thus, a stabilisation of the metabolism leading also to a decrease in autophagy.

Objective: Refeeding syndrome is a feared complication of refeeding patients with anorexia nervosa. There are now a number of controlled studies showing that refeeding with an initial high calorie count is more beneficial than cautious refeeding and is safe under continuous monitoring. However, there have yet not been studies in severe anorexia nervosa.Method: We present an observational study in two different samples. The first sample consists of those 1075 out of a total of 3230 patients with anorexia nervosa treated in our hospital within 4 years for whom a complete admission laboratory was available and who had an age of at least 18 years at admission. A risk score was calculated from the number of pathological laboratory values out of 12 parameters indicating either refeeding syndrome or health hazards related to malnutrition. The second sample was obtained from a special ward for patients with eating disorders medically at‐risk. During the period in question, 410 patients with anorexia nervosa were treated there. 142 patients had a BMI of 13 or less and at the same time a complete data set with the mentioned 12 laboratory parameters at admission and weekly in the following 4 weeks after admission.Results: The risk represented by the laboratory parameters is significantly and negatively correlated to BMI and much higher for the group of patients with a BMI below 13 than for those with a higher BMI (χ² sig < 0.000). The 142 patients in the special care unit gain an average of more than 4.1 kg within 4 weeks on the high‐calorie diet. With this rapid weight gain, the risk score decreases highly significantly. Neither hypophosphatemia nor rhabdomyolysis is found under phosphate substitution. Hyperhydration occurred often, which manifests itself in the drop in haematocrit by the second week.Discussion: Under thorough medical surveillance, supplementation of phosphate and thiamine, and substitution of electrolytes whenever necessary rapid renutrition appeared to be save even in extremely malnourished inpatients with anorexia nervosa. As measured by the laboratory values, the health status of the severely malnourished patients improves significantly on a high‐calorie diet. Except for hyperhydration, there was no evidence of a refeeding syndrome.