Effects of Transcranial Direct Current Stimulation Treatment for Anorexia Nervosa.

Background: Anorexia nervosa (AN) is a life-threatening illness with poor treatment outcomes. Although transcranial direct current stimulation (tDCS) is a promising non-invasive brain stimulation method, its effect in patients with AN remains unclear. Objective: This study investigated changes in maladaptive eating behavior, body mass index (BMI), and depression after 10 sessions of anodal tDCS over the left dorsolateral prefrontal cortex (DLPFC). Methods: In this double-blind, randomized controlled trial, 43 inpatients with AN were divided to receive either active (n = 22) or sham (n = 21) tDCS over the left DLPFC (anode F3/cathode Fp2, 2 mA for 30 min). All patients filled the Eating Disorder Examination Questionnaire (EDE-Q) and Zung Self-Rating Depression Scale (ZUNG), and their BMI was measured. These values were obtained repeatedly in four stages: (1) before tDCS treatment, (2) after tDCS treatment, (3) in the follow-up after 2 weeks, and (4) in the follow-up after 4 weeks. Results: Primary outcomes (EDE-Q) based on the ANOVA results do not show any between-group differences either after the active part of the study or in the follow-up. Secondary analysis reveals a reduction in some items of EDE-Q. Compared with sham tDCS, active tDCS significantly improved self-evaluation based on body shape (p < 0.05) and significantly decreased the need of excessive control over calorie intake (p < 0.05) in the 4-week follow-up. However, the results do not survive multiple comparison correction. In both sham and active groups, the BMI values improved, albeit not significantly. Conclusion: We did not observe a significant effect of tDCS over the left DLPFC on complex psychopathology and weight recovery in patients with AN. tDCS reduced the need to follow specific dietary rules and improved body image evaluation in patients with AN. Tests with a larger sample and different positions of electrodes are needed. Clinical Trial Registration: www.ClinicalTrials.gov, identifier: NCT03273205.

Altered Serum Immunological and Biochemical Parameters and Microbiota Composition in Patients With AN During Realimentation.

Anorexia nervosa (AN) is a life-threatening psychiatric disorder with not well-described pathogenesis. Besides the genetic and sociological factors, autoimmunity is also considered to take part in AN pathogenesis. We evaluated general serological factors showing the physiological state of 59 patients with AN at hospital admission and their discharge. We detected the altered levels of some general biochemical and immunological parameters. We also detected decreased levels of appetite-regulating alpha-melanocyte stimulating hormone (α-MSH) in patients at hospital admission. Moreover, elevated anti-α-MSH IgM levels and decreased anti-α-MSH IgA levels were observed in patients with AN. Therefore, we analyzed the gut microbiota composition with special focus on α-MSH antigen-mimetic containing microbes from the Enterobacteriaceae family. We correlated gut bacterial composition with anti-α-MSH Ig levels and detected decreasing IgG levels with increasing alpha diversity. The upregulation of pro-inflammatory cytokines IL-6, IL-17, and TNF-α were detected in patients with AN both prior and after hospitalization. We also evaluated the treatment outcome and improvement was observed in the majority of patients with AN. We provide new data about various serum biochemical parameters and their changes during the patients' hospitalization, with emphasis on the immune system, and its possible participation in AN pathogenesis.

The intestinal microbiota and metabolites in patients with anorexia nervosa.

Brain-gut microbiota interactions are intensively studied in connection with various neurological and psychiatric diseases. While anorexia nervosa (AN) pathophysiology is not entirely clear, it is presumably linked to microbiome dysbiosis. We aimed to elucidate the gut microbiota contribution in AN disease pathophysiology. We analyzed the composition and diversity of the gut microbiome of patients with AN (bacteriome and mycobiome) from stool samples before and after renourishment, and compared them to healthy controls. Further, levels of assorted neurotransmitters and short-chain fatty acids (SCFA) were analyzed in stool samples by MS and NMR, respectively. Biochemical, anthropometric, and psychometric profiles were assessed. The bacterial alpha-diversity parameter analyses revealed only increased Chao 1 index in patients with AN before the realimentation, reflecting their interindividual variation. Subsequently, core microbiota depletion signs were observed in patients with AN. Overrepresented OTUs (operation taxonomic units) in patients with AN taxonomically belonged to Alistipes, Clostridiales, Christensenellaceae, and Ruminococcaceae. Underrepresented OTUs in patients with AN were Faecalibacterium, Agathobacter, Bacteroides, Blautia, and Lachnospira. Patients exhibited greater interindividual variation in the gut bacteriome, as well as in metagenome content compared to controls, suggesting altered bacteriome functions. Patients had decreased levels of serotonin, GABA, dopamine, butyrate, and acetate in their stool samples compared to controls. Mycobiome analysis did not reveal significant differences in alpha diversity and fungal profile composition between patients with AN and healthy controls, nor any correlation of the fungal composition with the bacterial profile. Our results show the changed profile of the gut microbiome and its metabolites in patients with severe AN. Although therapeutic partial renourishment led to increased body mass index and improved psychometric parameters, SCFA, and neurotransmitter profiles, as well as microbial community compositions, did not change substantially during the hospitalization period, which can be potentially caused by only partial weight recovery.

Microbiota, Microbial Metabolites, and Barrier Function in A Patient with Anorexia Nervosa after Fecal Microbiota Transplantation.

The change in the gut microbiome and microbial metabolites in a patient suffering from severe and enduring anorexia nervosa (AN) and diagnosed with small intestinal bacterial overgrowth syndrome (SIBO) was investigated. Microbial gut dysbiosis is associated with both AN and SIBO, and therefore gut microbiome changes by serial fecal microbiota transplantation (FMT) is a possible therapeutic modality. This study assessed the effects of FMT on gut barrier function, microbiota composition, and the levels of bacterial metabolic products. The patient treatment with FMT led to the improvement of gut barrier function, which was altered prior to FMT. Very low bacterial alpha diversity, a lack of beneficial bacteria, together with a great abundance of fungal species were observed in the patient stool sample before FMT. After FMT, both bacterial species richness and gut microbiome evenness increased in the patient, while the fungal alpha diversity decreased. The total short-chain fatty acids (SCFAs) levels (molecules presenting an important source of energy for epithelial gut cells) gradually increased after FMT. Contrarily, one of the most abundant intestinal neurotransmitters, serotonin, tended to decrease throughout the observation period. Overall, gut microbial dysbiosis improvement after FMT was considered. However, there were no signs of patient clinical improvement. The need for an in-depth analysis of the donor´s stool and correct selection pre-FMT is evident.

Patient awareness, perception and attitude to contrast-enhanced CT examination: Implications for communication and compliance with patients' preferences.

BACKGROUND: Despite the high volume of contrast-enhanced computed tomography (CECT) examinations, there is limited awareness about its risks among patients and little is known about the influence of patient information sheets. OBJECTIVES: The objective of this study was to assess patients' awareness and perception of risks related to CECT examination and how they are influenced by an information sheet. MATERIAL AND METHODS: A total of 263 adult patients scheduled for a CECT examination completed a questionnaire. The first page evaluated patients' characteristics, their fear and awareness about examination-related risks, and source of information. Page 2 contained the Zung self-rating anxiety scale. After reading the information sheet, patients completed page 3 that surveyed how their awareness and fear had changed. RESULTS: Nearly half of the patients underestimated the risk of secondary malignancy (n = 121, 46%), or the risk of renal impairment (n = 110, 42%). The vast majority (n = 227, 86%) stated that they were not instructed to maintain fluid intake up to 1 h before the procedure. After reading the information sheet, patients generally corrected their knowledge, but 195 (74%) reported experiencing greater fear (p < 0.0001). Fear was more pronounced in younger female patients who had not undergone CT previously. Patients feared the result more than examination-related risks. Most patients (n = 204, 78%) would feel uncomfortable before receiving the examination result. CONCLUSIONS: Most patients do not assess risks related to CECT examination correctly. Although the information sheet improves patients' understanding of CECT-related risks, it lacks empathically delivered reassurance and increases their fear. Fast communication of examination results would make patients feel more comfortable.

Disturbances of mitochondrial parameters to distinguish patients with depressive episode of bipolar disorder and major depressive disorder.

BACKGROUND: Mitochondrial dysfunctions are implicated in the pathophysiology of mood disorders. We measured and examined the following selected mitochondrial parameters: citrate synthase (CS) activity, electron transport system (ETS) complex (complexes I, II, and IV) activities, and mitochondrial respiration in blood platelets. PATIENTS AND METHODS: The analyses were performed for 24 patients suffering from a depressive episode of bipolar affective disorder (BD), compared to 68 patients with MDD and 104 healthy controls. BD and unipolar depression were clinically evaluated using well-established diagnostic scales and questionnaires. RESULTS: The CS, complex II, and complex IV activities were decreased in the depressive episode of BD patients; complex I and complex I/CS ratio were significantly increased compared to healthy controls. We observed significantly decreased complex II and CS activities in patients suffering from MDD compared to controls. Decreased respiration after complex I inhibition and increased residual respiration were found in depressive BD patients compared to controls. Physiological respiration and capacity of the ETS were decreased, and respiration after complex I inhibition was increased in MDD patients, compared to controls. Increased complex I activity can be a compensatory mechanism for decreased CS and complex II and IV activities. CONCLUSION: We can conclude that complex I and its abnormal activity contribute to the defects in cellular energy metabolism during a depressive episode of BD. The observed parameters could be used in a panel of biomarkers that could selectively distinguish BD depression from MDD and can be easily examined from blood elements.

Mitochondrial Dysfunction in Blood Platelets of Patients with Manic Episode of Bipolar Disorder.

OBJECTIVES: The bipolar affective disorder (BAD) pathophysiology is multifactorial and has not been fully clarified. METHOD: We measured selected mitochondrial parameters in peripheral blood components. The analyses were performed for patients suffering from a manic episode during remission and were compared to those performed for healthy controls. BAD was clinically evaluated using well-established diagnostic scales and questionnaires. Mitochondrial respiration was examined in intact and permeabilized blood platelets using high-resolution respirometry. The citrate synthase (CS) and electron transport system (ETS) complex (complex I, II, and IV) activities were examined in platelets. RESULTS: The CS, complex II and complex IV activities were decreased in the BAD patients, complex I activity was increased, and the ratio of complex I to CS was significantly increased. In the intact platelets, respiration after complex I inhibition and residual oxygen consumption were decreased in the BAD patients compared to the healthy controls. In the permeabilized platelets, a decreased ETS capacity was found in the BAD patients. No significant differences were found between BAD patients in mania and remission. CONCLUSION: Increased complex I activity can be a compensatory mechanism for decreased CS and complex II and IV activities. We conclude that complex I and its abnormal activity contribute to defects in cellular energy metabolism during a manic episode and that the deficiency in the complex's functioning, but not the availability of oxidative phosphorylation substrates, seems to be responsible for the decreased ETS capacity in BAD patients. The observed parameters can be further evaluated as 'trait' markers of BAD.

Violence in persons with and without psychosis in the Czech Republic: risk and protective factors.

PURPOSE: To prevent violence among persons with psychosis, further knowledge of the correlates and risk factors is needed. These risk factors may vary by nation. PATIENTS AND METHODS: This study examined factors associated with violent assaults in 158 patients with psychosis and in a matched control sample of 158 adults without psychosis in the Czech Republic. Participants completed interviews and questionnaires to confirm diagnoses, report on aggressive behavior, current and past victimization, and substance use. Additional information was collected from collateral informants and clinical files. Multiple regression analyses were conducted to identify factors that were independently associated with committing an assault in past 6 months. RESULTS: The presence of a psychotic disorder was associated with an increased risk of assaults (OR =3.80; 95% CI 2.060-7.014). Additional risk factors in persons with and without psychosis included recent physical victimization (OR =7.09; 95% CI 3.922-12.819), childhood maltreatment (OR =3.15; 95% CI 1.877-5.271), the level of drug use (OR =1.13; 95% CI 1.063-1.197), and the level of alcohol use (OR =1.04; 95% CI 1.000-1.084). Increasing age (OR =0.96; 95% CI 0.942-0.978) and employment (OR =0.30; 95% CI 0.166-0.540) were protective factors. Except for drug use, which appeared to have greater effect on violence in the group without psychosis, there were no major differences between patients and controls in these risk and protective factors. To our knowledge, this is the first published comparison of assault predictors between schizophrenia patients and matched controls. CONCLUSION: Recent physical victimization was the strongest predictor of assaults. Our findings are consistent with the emerging empirical evidence pointing to the very important role of victimization in eliciting violent behavior by the victims. Some current prediction instruments may underestimate the risk of violent behavior as they take little account of current victimization. Although psychosis per se elevates the risk of violence, other risk and protective factors for violence in persons with psychosis and comparison group are largely similar.

The predictive value of computed tomography in the detection of reflux esophagitis in patients undergoing upper endoscopy.

BACKGROUND: Reflux esophagitis (RE) may mimic symptoms requiring cross-sectional imaging. METHODS: From 565 patients who had CT and esophagogastroduodenoscopy within four days apart, CT scans of 72 patients with RE confirmed by esophagogastroduodenoscopy and 108 matched patients without RE were evaluated for distal esophageal wall characteristics. RESULTS: In RE patients the distal esophageal wall thickness was greater (5.2±2.0mm) compared to patients without RE (3.5±1.2mm, p<0.0001) with AUC of 0.78 and 56% sensitivity, 88% specificity for a 5.0mm cut-off. CONCLUSIONS: There is a moderate association between distal esophageal wall thickness on CT and RE diagnosed by esophagogastroduodenoscopy as the reference standard.

Growing number of emergency cranial CTs in patients with head injury not justified by their clinical need.

BACKGROUND: Computed tomography (CT) is widely available in most hospitals, usually 24 h a day, which results in an expansion of its indications, sometimes beyond medically justifiable extent. AIM: To evaluate trends in emergency cranial CTs in a general university hospital during the last 15 years. METHODS: We conducted a database search for emergency cranial CTs between January 2000 and December 2015 that were performed in patients after head injury on weekends and bank holidays and between 8 P.M. and 6 A.M. on workdays. The numbers were compared with demographic data, the number of hospital beds, and total number of CT examinations. RESULTS: The annual number of emergency cranial CTs increased 5.5 times from 124 to 679 with a sharp increase since 2013. This trend showed a negative correlation with the number of hospital beds (r = -0.88, p = 0.0001), the proportion of important findings on cranial CT (r = -0.74, p = 0.0010), or the proportion of patients indicated for cranial CT by NICE 2014 criteria (r = -0.90, p < 0.0001) and positive correlation with the proportion of inebriated patients (r = 0.94, p < 0.0001), and their average GCS score (r = 0.92, p < 0.0001). Compared to the number of emergency cranial CTs, the slope of regression lines for all trends was significantly different (p < 0.001) apart from the number of inebriated patients (p = 0.062). CONCLUSIONS: The increase in the emergency cranial CTs cannot be entirely justified by their clinical need. We assume that this is the result of an absent support of adherence to the guidelines in the legislation together with a medicolegally unpredictable environment.

Computed Tomography Colonography Phantom: Construction, Validation and Literature Review.

BACKGROUND: Several dedicated computed tomography (CT) colonography phantoms have been described previously. OBJECTIVES: To compare their pros and cons and describe the construction of a dedicated phantom that can be easily manufactured. MATERIALS AND METHODS: We found 15 different phantom designs by literature search and compared their advantages and disadvantages based on their description and images. We tested various materials for density and mechanical properties and constructed a phantom from polypropylene pipes (30 mm and 50 mm in diameter, 52 cm in length). Haustral folds were created by heat shaping and 39 intermediate sessile polyps with a target size of 6-10 mm and two flat lesions were created from silicone. Nine polyps were attached to a fold. The model was placed in a 30-cm barrel filled with water to simulate attenuation of human body. Attenuation of polyps was compared to intermediate polyps found in patients. RESULTS: None of the earlier colonic phantoms found in the literature incorporated all the properties that would ensure both reproducibility and validity of the model (including a rigid wall, density of the wall and polyps similar to human colon, at least two levels of distension and durability). In the present phantom, the average size of sessile polyps was 8.6 ± 0.9 mm and their density was 53 ± 24 HU. We found no significant difference in polyp density between simulated polyps in the phantom and polyps in human subjects (P = 0.70). All polyps, with the exception of one flat lesion, were detected by computer aided detection. CONCLUSION: We constructed and validated a CT colonography phantom with correct density allowing performance of reproducible experiments.