[Clinical significance of neuroendocrine tumors : Incidence, symptoms, diagnosis, stage, and prognostic factors and their influence on disease management]. / Klinische Bedeutung von neuroendokrinen Tumoren : Häufigkeit, Symptome, Diagnose und Stadien und prognostische Faktoren und deren Einfluss auf das Krankheitsmanagement.

BACKGROUND: Neuroendocrine neoplasms (NEN) are heterogenous with an increasing incidence in recent years. OBJECTIVES: Overview on incidence, symptoms, diagnostics, grading, imaging and prognostic determinants, including factors having an impact on therapeutic management. METHODS: Review on current literature, including original articles, reviews, guidelines and expert opinions. RESULTS: NEN are mainly located in the gastrointestinal tract and their incidence has increased in recent years, mainly due to improved diagnostics, e.g., cross-sectional imaging. Clinical characteristics include hormone excess syndromes (carcinoid syndrome). Laboratory markers such as chromogranin A are commonly used as part of routine diagnostics, followed by endoscopic and endosonographic procedures, which also allow biopsies to be obtained. Tumor spread can be determined by contrast-enhanced computed tomography/magnetic resonance imaging (CT/MRI) or somatostatin receptor (SSRT)-PET/CT (positron emission tomography). Prognostic factors include Ki67 index, type, and grading. Resection with curative intent is the therapy of choice. In a metastasized setting, SSRT-directed treatment approaches are favored, while in dedifferentiated NEN, conventional chemotherapy is needed. CONCLUSION: A broad diagnostic armamentarium can be offered to NEN patients and the improved diagnostic procedures have most likely caused a raising incidence in recent years. Among others, prognostic factors are Ki67 and NEN subtypes; these clinical determinants also have an impact on patient management.

Correction: Is a higher frequency of esophageal dilations more effective in treating benign esophageal strictures? Retrospective, multicenter study.

[This corrects the article DOI: 10.1055/a-2117-8197.].

Terlipressin therapy is associated with increased risk of colonisation with multidrug-resistant bacteria in patients with decompensated cirrhosis.

BACKGROUND: Patients with cirrhosis are susceptible to develop bacterial infections that trigger acute decompensation (AD) and acute-on-chronic liver failure (ACLF). Infections with multidrug-resistant organisms (MDRO) are associated with deleterious outcome. MDRO colonisation frequently proceeds MDRO infections and antibiotic therapy has been associated with MDRO colonisation. AIM: The aim of the study was to assess the influence of non-antibiotic medication contributing to MDRO colonisation. METHODS: Three hundred twenty-four patients with AD and ACLF admitted to the ICU of Frankfurt University Hospital with MDRO screening were included. Regression models were performed to identify drugs associated with MDRO colonisation. Another cohort (n = 129) from Barcelona was included to validate. A third multi-centre cohort (n = 203) with metagenomic sequencing data of stool was included to detect antibiotic resistance genes. RESULTS: A total of 97 patients (30%) were identified to have MDRO colonisation and 35 of them (11%) developed MDRO infection. Patients with MDRO colonisation had significantly higher risk of MDRO infection than those without (p = 0.0098). Apart from antibiotic therapy (odds ratio (OR) 2.91, 95%-confidence interval (CI) 1.82-4.93, p < 0.0001), terlipressin therapy in the previous 14 days was the only independent covariate associated with MDRO colonisation in both cohorts, the overall (OR 9.47, 95%-CI 2.96-30.23, p < 0.0001) and after propensity score matching (OR 5.30, 95%-CI 1.22-23.03, p = 0.011). In the second cohort, prior terlipressin therapy was a risk factor for MDRO colonisation (OR 2.49, 95% CI 0.911-6.823, p = 0.075) and associated with risk of MDRO infection during follow-up (p = 0.017). The validation cohort demonstrated that antibiotic inactivation genes were significantly associated with terlipressin administration (p = 0.001). CONCLUSIONS: Our study reports an increased risk of MDRO colonisation in patients with AD or ACLF, who recently received terlipressin therapy, while other commonly prescribed non-antibiotic co-medications had negligible influence. Future prospective trials are needed to confirm these results.

Is a higher frequency of esophageal dilations more effective in treating benign esophageal strictures? Retrospective, multicenter study.

Background and study aims There is still a lack of evidence-based recommendations concerning endoscopic bougienage in benign esophageal strictures. Our study aimed to assess the relevance of the time interval between endoscopic dilation (ED) sessions with regard to endoscopic and clinical response. Patients and methods We performed a retrospective study including patients treated with endoscopic bougienage for a benign esophageal stricture in two German centers. Primary endpoint was the number of ED until freedom from dysphagia was achieved. Secondary endpoints were analyses on reaching a diameter of 15 mm and on achieving clinical freedom from symptoms. Results Between April 2014 and March 2020, bougienage was used as the primary treatment for benign esophageal strictures in 238 patients (194 patients in Center 1; 44 patients in Center 2). Both centers differed in their endoscopic bougienage regime: Center 1 was characterized by a higher frequency of interventions compared to Center 2 (median: 2 days [range 1-28] vs. 10 days [range 1-41]; P <0.001). Clinical response was achieved significantly earlier using the high-frequency regimen in all patients except for those with post-radiogen strictures, who clinically benefited from a low-frequency ED program. Accordingly, patients receiving higher-frequency ED reached a significantly larger post-dilation diameter and considerably larger diameter differences. Conclusions The results of our study demonstrate that a treatment concept consisting of higher-frequency bougienages seems to be more effective in treating most types of esophageal stricture. Radiogenic strictures were the only types of stenoses that benefited from a lower frequency ED program.

Appropriate and mindful measurement of serum calcitonin in patients with thyroid nodules. A white paper.

Medullary thyroid carcinoma (MTC) is an infrequent thyroid malignancy that is often diagnosed at advanced stage with consequent poor prognosis. Thus, the earlier the diagnosis of MTC, the better the prognosis. Unfortunately, the preoperative detection of MTC remains challenging in clinical practice. In fact, while ultrasound and fine-needle aspiration cytology have suboptimal performance in this context, measuring serum calcitonin (Ctn), fully recognized as the most reliable test to detect MTC, is not universally accepted as routine test in all patients with thyroid nodule(s). The authors of this paper reappraise critically the matter of Ctn measurement in view of the recent advancements in the literature to point out the essential information to be known, and then to prepare an easy-to-use guide for clinicians to appropriately consider the measurement of serum Ctn during clinical practice.

Short Versus Long Antibiotic Therapy and Risk of Recurrence of Acute Cholangitis Due to Malignant Biliary Strictures.

Malignancies can cause severe stenosis of the biliary tract and therefore predispose a patient to bacterial cholangitis. Upon endoscopic drainage, antibiotic therapy (AT) is performed according to individual clinical judgement, as the optimal duration of AT is unclear to date, especially in the case of multidrug-resistant organisms (MDROs). In a case-based retrospective study, patients with malignant biliary strictures and acute cholangitis were included upon endoscopic retrograde cholangiography (ERC). The outcome of cases treated with short AT (≤6 days) was compared to that of long AT (≥7 days). Recurrent cholangitis (RC) before scheduled stent exchange was the primary end point. In total, 124 patients were included, with 183 cases of proven cholangitis in total. The overall median duration of AT was 7 days (range 1-20), with 74 cases (40%) receiving short AT and 109 (60%) receiving long AT. Short AT was not an independent risk factor for RC (HR = 0.66, p > 0.2), while colonization with MDROs was associated with a higher risk of RC (HR = 2.21, p = 0.005). Placement of a metal stent was associated with minor risk of RC (HR = 0.4, p = 0.038). In conclusion, short AT is possible in selected patients with non-severe cholangitis and malignant biliary strictures. Scheduled screening for MDROs is recommended and placement of a metal stent should be performed if possible.

Characteristics, clinical course and outcome of ventilated patients at a non-surgical intensive care unit in Germany: a single-centre, retrospective observational cohort analysis.

OBJECTIVES: The objective of this study was to evaluate epidemiological characteristics, clinical course and outcome of mechanically ventilated non-surgical intensive care unit (ICU) patients, with the aim of improving the strategic planning of ICU capacities. DESIGN: We conducted a retrospective observational cohort analysis. Data from mechanically ventilated intensive care patients were obtained by investigating electronic health records. The association between clinical parameters and ordinal scale data of clinical course was evaluated using Spearman correlation and Mann-Whitney U test. Relations between clinical parameters and in-hospital mortality rates were examined using binary logistic regression analysis. SETTING: A single-centre study at the non-surgical ICU of the University Hospital of Frankfurt, Germany (tertiary care-level centre). PARTICIPANTS: All cases of critically ill adult patients in need of mechanical ventilation during the years 2013-2015 were included. In total, 932 cases were analysed. RESULTS: From a total of 932 cases, 260 patients (27.9%) were transferred from peripheral ward, 224 patients (24.1%) were hospitalised via emergency rescue services, 211 patients (22.7%) were admitted via emergency room and 236 patients (25.3%) via various transfers. In 266 cases (28.5%), respiratory failure was the reason for ICU admission. The length of stay was higher in non-geriatric patients, patients with immunosuppression and haemato-oncological disease or those in need of renal replacement therapy. 431 patients died, which corresponds to an all-cause in-hospital mortality rate of 46.2%. 92 of 172 patients with presence of immunosuppression (53.5%), 111 of 186 patients (59.7%) with pre-existing haemato-oncological disease, 27 of 36 patients (75.0%) under extracorporeal membrane oxygenation (ECMO) therapy, and 182 of 246 patients (74.0%) undergoing renal replacement therapy died. In logistic regression analysis, these subgroups and older age were significantly associated with higher mortality rates. CONCLUSIONS: Respiratory failure was the main reason for ventilatory support at this non-surgical ICU. Immunosuppression, haemato-oncological diseases, the need for ECMO or renal replacement therapy and older age were associated with higher mortality.

Treatment of Non-Anastomotic Biliary Strictures after Liver Transplantation: How Effective Is Our Current Treatment Strategy?

BACKGROUND: Non-anastomotic biliary strictures (NAS) are a common cause of morbidity and mortality after liver transplantation. METHODS: All patients with NAS from 2008 to 2016 were retrospectively analyzed. The success rate and overall mortality of an ERCP-based stent program (EBSP) were the primary outcomes. RESULTS: A total of 40 (13.9%) patients with NAS were identified, of which 35 patients were further treated in an EBSP. Furthermore, 16 (46%) patients terminated EBSP successfully, and nine (26%) patients died during the program. All deaths were caused by cholangitis. Of those, one (11%) patient had an extrahepatic stricture, while the other eight patients had either intrahepatic (3, 33%) or combined extra- and intrahepatic strictures (5, 56%). Risk factors of overall mortality were age (p = 0.03), bilirubin (p < 0.0001), alanine transaminase (p = 0.006), and aspartate transaminase (p = 0.0003). The median duration of the stent program was 34 months (ITBL: 36 months; IBL: 10 months), and procedural complications were rare. CONCLUSIONS: EBSP is safe, but lengthy and successful in only about half the patients. Intrahepatic strictures were associated with an increased risk of cholangitis.

Risk Factors and Role of Antibiotic Prophylaxis for Wound Infections after Percutaneous Endoscopic Gastrostomy.

BACKGROUND AND STUDY AIM: The incidence of wound infections after percutaneous endoscopic gastrostomy (PEG) varies widely in recent studies. The present study systematically investigates the underlying risk factors for the development of wound infections in a large cohort of patients over a long-term follow-up period. PATIENTS AND METHODS: A retrospective cohort study of patients undergoing PEG insertion using either the pull or push technique was conducted and patients followed up for 3 years. Tube-related wound infections were identified, and pathogens regularly cultured from wound swabs. Adjusted analysis was performed via univariate and multivariate logistic regression analysis. RESULTS: 616 patients were included in this study. A total of 25% percent of patients developed wound infections upon PEG tube insertion and 6.5% showed recurrent infections. Nicotine abuse (p = 0.01), previous ischemic stroke (p = 0.01) and head and neck cancer (p < 0.001) showed an increased risk for wound infection after PEG placement. Moreover, radio-chemotherapy was associated with the occurrence of wound infections (p < 0.001). Infection rates were similar between pull and push cohorts. The most common bacterial pathogen detected was Enterobacterales (19.2%). Staphylococcus aureus, Pseudomonas aeruginosa and enterococci were frequently detected in recurrent infection (14.2%, 11.4% and 9.6%, respectively). Antibiotic prophylaxis showed no effect on infection rates. CONCLUSIONS: Wound infections after PEG placement are common and occasionally occur as recurrent infections. There is potential for improvement in everyday clinical practice, particularly regarding antibiotic prophylaxis in accordance with guidelines.

Fluorescence confocal microscopy on liver specimens for full digitization of transplant pathology.

Fluorescence confocal microscopy (FCM) is a rapidly evolving tool that provides real-time virtual HE images of native tissue. Data about the potential of FCM as an alternative to frozen sections for the evaluation of donor liver specimens are lacking so far. The aim of the current study was to determine the value of FCM in liver specimens according to the criteria of the German Society for Organ Procurement. In this prospective study, conventional histology and FCM scans of 50 liver specimens (60% liver biopsies, 26% surgical specimens, and 14% donor samples) were evaluated according to the German Society for Organ Procurement. A comparison of FCM scans and conventional frozen sections revealed almost perfect levels of agreement for cholangitis (κ = 0.877), fibrosis (κ = 0.843), and malignancy (κ = 0.815). Substantial levels of agreement could be obtained for macrovesicular steatosis (κ = 0.775), inflammation (κ = 0.763), necrosis (κ = 0.643), and steatohepatitis (κ = 0.643). Levels of agreement were moderate for microvesicular steatosis (κ = 0.563). The strength of agreement between frozen sections and FCM was superior to the comparison of conventional HE and FCM imaging. We introduce FCM as a potential alternative to the frozen section that may represent a novel approach to liver transplant pathology where timely feedback is crucial and the deployment of human resources is becoming increasingly difficult.

Glucocorticoid withdrawal and glucocorticoid-induced adrenal insufficiency: Study protocol of the randomized controlled «TOASST" (Taper Or Abrupt Steroid STop) multicenter trial.

BACKGROUND: Despite the widespread use of glucocorticoids in inflammatory and autoimmune disorders, there is uncertainty about the safe cessation of long-term systemic treatment, as data from prospective trials are largely missing. Due to potential disease relapse or glucocorticoid-induced hypocortisolism, the drug is often tapered to sub-physiological doses rather than stopped when the underlying disease is clinically stable, increasing the cumulative drug exposure. Conversely, the duration of exposure to glucocorticoids should be minimized to lower the risk of side effects. METHODS: We designed a multicenter, randomized, triple-blinded, placebo-controlled trial to test the clinical noninferiority of abrupt glucocorticoid stop compared to tapering after ≥28 treatment days with ≥420 mg cumulative and ≥7.5 mg mean daily prednisone-equivalent dose. 573 adult patients treated systemically for various disorders will be included after their underlying disease has been stabilized. Prednisone in tapering doses or matching placebo is administered over 4 weeks. A 250 mg ACTH-test, the result of which will be revealed a posteriori, is performed at study inclusion; all patients are instructed on glucocorticoid stress cover dosing. Follow-up is for 6 months. The composite primary outcome measure is time to hospitalization, death, initiation of unplanned systemic glucocorticoid therapy, or adrenal crisis. Secondary outcomes include the individual components of the primary outcome, cumulative glucocorticoid doses, signs and symptoms of hypocortisolism, and the performance of the ACTH test in predicting the clinical outcome. Cox proportional hazard, linear, and logistic regression models will be used for statistical analysis. CONCLUSION: This trial aims to demonstrate the clinical noninferiority and safety of abrupt treatment cessation after ≥28 days of systemic glucocorticoid therapy in patients with stabilized underlying disease. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03153527; EUDRA-CT: 2020-005601-48 https://clinicaltrials.gov/ct2/show/NCT03153527?term=NCT03153527&draw=2&rank=1.

[Thyroid disease during pregnancy]. / Schilddrüsenerkrankungen in der Schwangerschaft.

Thyroid disease is the second most endocrinopathy during pregnancy 1. Thyroid dysfunction affects 2-3 % of pregnant women 2. Early diagnosis and initiation of therapy are important due to the potential complications in both mother and fetus. This article provides an overview of current recommendations regarding thyroid diagnostics and constellations during pregnancy that require therapy.

Pulmonary impairment independently determines mortality in critically ill patients with acute-on-chronic liver failure.

BACKGROUND & AIMS: In ACLF patients, an adequate risk stratification is essential, especially for liver transplant allocation, since ACLF is associated with high short-term mortality. The CLIF-C ACLF score is the best prognostic model to predict outcome in ACLF patients. While lung failure is generally regarded as signum malum in ICU care, this study aims to evaluate and quantify the role of pulmonary impairment on outcome in ACLF patients. METHODS: In this retrospective study, 498 patients with liver cirrhosis and admission to IMC/ICU were included. ACLF was defined according to EASL-CLIF criteria. Pulmonary impairment was classified into three groups: unimpaired ventilation, need for mechanical ventilation and defined pulmonary failure. These factors were analysed in different cohorts, including a propensity score-matched ACLF cohort. RESULTS: Mechanical ventilation and pulmonary failure were identified as independent risk factors for increased short-term mortality. In matched ACLF patients, the presence of pulmonary failure showed the highest 28-day mortality (83.7%), whereas mortality rates in ACLF with mechanical ventilation (67.3%) and ACLF without pulmonary impairment (38.8%) were considerably lower (p < .001). Especially in patients with pulmonary impairment, the CLIF-C ACLF score showed poor predictive accuracy. Adjusting the CLIF-C ACLF score for the grade of pulmonary impairment improved the prediction significantly. CONCLUSIONS: This study highlights that not only pulmonary failure but also mechanical ventilation is associated with worse prognosis in ACLF patients. The grade of pulmonary impairment should be considered in the risk assessment in ACLF patients. The new score may be useful in the selection of patients for liver transplantation.

Impact of colonization with multidrug-resistant organisms on antibiotic prophylaxis in patients with cirrhosis and variceal bleeding.

BACKGROUND: The efficacy of antibiotic prophylaxis to prevent rebleeding or infection after variceal bleeding in patients with liver cirrhosis colonized with multidrug-resistant organisms (MDROs) is unknown. METHODS: In this retrospective study, patients with liver cirrhosis and endoscopically confirmed variceal bleeding who were treated at a tertiary care center in Germany and were screened for MDROs at the time of bleeding were eligible for inclusion. Efficacy of antibiotic prophylaxis was evaluated in patients stratified according to microbiological susceptibility testing. RESULTS: From 97 patients, the majority had decompensated liver cirrhosis (median MELD Score 17) and ACLF was present in half of the patients (47.4%). One third of patients were colonized with MDRO at baseline. De-novo infection until day 10 or the combination of de-novo infection or rebleeding were comparable among both groups (p = 0.696 and p = 0.928, log-rank-test). Risk of de-novo infection or rebleeding was not significantly increased in patients who received antibiotic prophylaxis that did not cover the MDRO found upon baseline screening. Acute-on-chronic liver failure at baseline was the strongest and only independent risk factor that was associated with both outcomes (OR 5.52, 95%-CI 1.48-20.61, p = 0.011 and OR 11.5, 95%-CI 2.70-48.62, p<0.001). Neither MDRO colonization at baseline nor covering all detected MDRO with antibiotic prophylaxis (i.e. "adequate" prophylaxis) impacted transplant-free survival. Again, the presence of ACLF was the strongest independent risk factor associated with mortality (OR 9.85, 95%-CI 3.58-27.12, p<0.0001). CONCLUSION: In this study, MDRO colonization did not increase the risk of rebleeding, infections nor death, even if antibiotic prophylaxis administered did not cover all MDRO detected at MDRO screening. Patients with ACLF had an increased risk of bleeding, infections and death.

Impact of a shorter replacement interval of plastic stents on premature stent exchange rate in benign and malignant biliary strictures.

BACKGROUND AND AIM: The main disadvantage of plastic stents is the high rate of stent occlusion. The usual replacement interval of biliary plastic stents is 3 months. This study aimed to investigate if a shorter interval of 6-8 weeks impacts the median premature exchange rate (mPER) in benign and malignant biliary strictures. METHODS: All cases with endoscopic retrograde cholangiopancreatography (ERCP) and plastic stent placement were retrospectively analyzed since establishing an elective replacement interval of every 6-8 weeks at our institution and mPER was determined. RESULTS: A total of 3979 ERCPs (1199 patients) were analyzed, including 1262 (31.7%) malignant and 2717 (68.3%) benign cases, respectively. The median stent patency (mSP) was 41 days (range 14-120) for scheduled stent exchanges, whereas it was 17 days (1-75) for prematurely exchanged stents. The mPER was significantly higher for malignant (28.1%, 35-50%) compared with benign strictures (15.2%, 10-28%), P < 0.0001, respectively. mSP was significantly shorter in cases with only one stent (34 days [1-87] vs 41 days [1-120]) and in cases with only a 7-Fr stent (28 days [2-79]) compared with a larger stent (34 days [1-87], P = 0.001). Correspondingly, mPER was significantly higher in cases with only one stent (23% vs 16.2%, P < 0.0001) and only a 7-Fr stent (31.3% vs 22.4%, P = 0.03). CONCLUSION: A shorter replacement interval does not seem to lead to a clinically meaningful reduction of mPER in benign and malignant strictures. Large stents and multiple stenting should be favored as possible.

Distinct clinical phenotypes in a family with a novel truncating MEN1 frameshift mutation.

BACKGROUND: MEN1 mutations can inactivate or disrupt menin function and are leading to multiple endocrine neoplasia type 1, a rare heritable tumor syndrome. CASE PRESENTATION: We report on a MEN1 family with a novel heterozygous germline mutation, c.674delG; p.Gly225Aspfs*56 in exon 4 of the MEN1 gene. Diagnosis and clinical phenotyping of MEN1 was established by laboratory tests, ultrasound, biopsy, MRI imaging and endosonography. The clinical course of the disease was followed in the index patient and her family members for eight years. The mutation was associated with distinct clinical phenotypes in the index patient and three family members harboring p.Gly225Aspfs*56. Family members affected showed primary hyperparathyroidism but variable patterns of associated endocrine tumors, adrenal cortical adenomas, prolactinoma, multifocal pancreatic neuroendocrine tumors, insulinoma and nonsecretory neuroendocrine tumors of the pancreas. The mutation c.674delG; p.Gly225Aspfs*56 leads to a frameshift from codon 225 with early truncation of the menin protein. In silico analysis predicts loss of multiple protein-menin interactions in p.Gly225Aspfs*56, potentially rendering menin insufficient to control cell division and replication. However, no aggressive neuroendocrine tumors were observed in the follow-up of this family. CONCLUSIONS: We report a novel heterozygous MEN1 frameshift mutation, potentially causing (at least partial) inactivation of menin tumor suppression potential but lacking a genotype-phenotype correlation. Our study highlights the importance of personalized care with appropriate testing and counseling in MEN1 families.

Application of Contrast-Enhanced Ultrasound to Detect Hepatic Hydrothorax in Patients with Liver Cirrhosis.

PURPOSE: Hepatic hydrothorax (HH) is defined as transudate in the pleural cavity in patients with decompensated liver cirrhosis (DC) without concomitant cardiopulmonary or pleural disease. It is associated with high short-term mortality. HH can evolve via translocation through diaphragmatic gaps. The aim of this study was to evaluate the feasibility and safety of injecting ultrasound contrast medium into the peritoneal cavity to detect HH. MATERIALS AND METHODS: This study included patients with concomitant ascites and pleural effusion who were admitted to our hospital between March 2009 and February 2019. A peritoneal catheter was inserted and ultrasound contrast medium was injected into the peritoneal cavity. In parallel, the peritoneal and pleural cavities were monitored for up to 10 minutes. RESULTS: Overall, 43 patients were included. The median age was 60 years and the majority of patients were male (n = 32, 74 %). Most patients presented with right-sided pleural effusion (n = 32, 74 %), 3 (7 %) patients with left-sided and 8 (19 %) patients had bilateral pleural effusion. In 12 (28 %) patients ascites puncture was not safe due to low volume ascites. Thus, the procedure could be performed in 31 (72 %) patients. No adverse events occurred. In 16 of 31 (52 %) patients we could visualize a trans-diaphragmic flow of microbubbles. The median time until transition was 120 seconds. CONCLUSION: Our clinical real-world experience supports the safety and feasibility of intraperitoneal ultrasound contrast medium application to detect HH in patients with DC, as a non-radioactive real-time visualization of HH. Our study comprises the largest cohort and longest experience using this method to date.

Short-term fasting in glioma patients: analysis of diet diaries and metabolic parameters of the ERGO2 trial.

PURPOSE: The prospective, randomized ERGO2 trial investigated the effect of calorie-restricted ketogenic diet and intermittent fasting (KD-IF) on re-irradiation for recurrent brain tumors. The study did not meet its primary endpoint of improved progression-free survival in comparison to standard diet (SD). We here report the results of the quality of life/neurocognition and a detailed analysis of the diet diaries. METHODS: 50 patients were randomized 1:1 to re-irradiation combined with either SD or KD-IF. The KD-IF schedule included 3 days of ketogenic diet (KD: 21-23 kcal/kg/d, carbohydrate intake limited to 50 g/d), followed by 3 days of fasting and again 3 days of KD. Follow-up included examination of cognition, quality of life and serum samples. RESULTS: The 20 patients who completed KD-IF met the prespecified goals for calorie and carbohydrate restriction. Substantial decreases in leptin and insulin and an increase in uric acid were observed. The SD group, of note, had a lower calorie intake than expected (21 kcal/kg/d instead of 30 kcal/kg/d). Neither quality of life nor cognition were affected by the diet. Low glucose emerged as a significant prognostic parameter in a best responder analysis. CONCLUSION: The strict caloric goals of the ERGO2 trial were tolerated well by patients with recurrent brain cancer. The short diet schedule led to significant metabolic changes with low glucose emerging as a candidate marker of better prognosis. The unexpected lower calorie intake of the control group complicates the interpretation of the results. Clinicaltrials.gov number: NCT01754350; Registration: 21.12.2012.

[Autoimmune thyroid disease]. / Autoimmunthyreoiditis.

Autoimmune thyroiditis (AIT) is not only one of the most prevalent human autoimmune diseases, but also the most frequent cause of primary hypothyroidism. It is characterized by lymphocytic infiltration of the thyroid gland with subsequent gradual destruction and fibrous replacement of thyroid tissue. Genetic predisposition, epigenetic modifications and environmental factors are suspected as disease triggers. Signs and symptoms of hypothyroidism include fatigue, bradycardia, constipation and cold intolerance. In subclinical hypothyroidism, symptoms may be absent. The diagnosis of AIT is based on the presence of antibodies against thyroid specific antigens, primarily anti-thyroid peroxidase antibodies and on a sonographically proven reduced echogenicity of the thyroid parenchyma. The diagnosis of concomitant hypothyroidism is primarily based on clinical signs and symptoms as well as measurement of thyroid-stimulating hormone (TSH)-concentration. Subclinical hypothyroidism is characterized by elevated TSH with normal serum free thyroxine (fT4) and triiodothyronine (fT3) levels, while in manifest hypothyroidism serum fT4 and fT3 levels are reduced. Levothyroxine (LT4) treatment in subclinical hypothyroidism is a controversy in the scientific literature and should be discussed individually. It not only depends on the level of TSH-elevation, but also on other factors, such as patient age, presence of comorbidities and clinical symptoms of hypothyroidism. In contrast, overt hypothyroidism and subclinical hypothyroidism with a TSH-level > 10 mIU/L is a strong indication for LT4 administration, aiming at rapid achievement of euthyroidism. In patients with dissatisfaction due to persistence of symptoms despite optimal LT4-treatment LT4/T3-combination therapy should be considered, based on expert opinion.