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.

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.

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.

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.

The presence of liver cirrhosis is a strong negative predictor of survival for patients admitted to the intensive care unit - Cirrhosis in intensive care patients.

BACKGROUND AND AIMS: Liver cirrhosis is a systemic disease that substantially impacts the body's physiology, especially in advanced stages. Accordingly, the outcome of patients with cirrhosis requiring intensive care treatment is poor. We aimed to analyze the impact of cirrhosis on mortality of intensive care unit (ICU) patients compared to other frequent chronic diseases and conditions. METHODS: In this retrospective study, patients admitted over three years to the ICU of the Department of Medicine of the University Hospital Frankfurt were included. Patients were matched for age, gender, pre-existing conditions, simplified acute physiology score (SAPS II), and therapeutic intervention scoring system (TISS). RESULTS: A total of 567 patients admitted to the ICU were included in the study; 99 (17.5 %) patients had liver cirrhosis. A total of 129 patients were included in the matched cohort for the sensitivity analysis. In-hospital mortality was higher in cirrhotic patients than non-cirrhotic patients (p < 0.0001) in the entire and matched cohort. Liver cirrhosis remained one of the strongest independent predictors of in-hospital mortality (entire cohort p = 0.001; matched cohort p = 0.03) along with dialysis and need for transfusion in the multivariate logistic regression analysis. Furthermore, in the cirrhotic group, the need for kidney replacement therapy (p < 0.001) and blood transfusion (p < 0.001) was significantly higher than in the non-cirrhotic group.  CONCLUSIONS: In the presented study, liver cirrhosis was one of the strongest predictors of in-hospital mortality in patients needing intensive care treatment along with dialysis and the need for ventilation. Therefore, concerted efforts are needed to improve cirrhotic patients' outcomes, prevent disease progression, and avoid complications with the need for ICU treatment in the early stages of the disease.

Evaluation of the Integrated Pulmonary Index® during non-anesthesiologist sedation for percutaneous endoscopic gastrostomy.

Standard monitoring of heart rate, blood pressure and arterial oxygen saturation during endoscopy is recommended by current guidelines on procedural sedation. A number of studies indicated a reduction of hypoxic (art. oxygenation < 90% for > 15 s) and severe hypoxic events (art. oxygenation < 85%) by additional use of capnography. Therefore, U.S. and the European guidelines comment that additional capnography monitoring can be considered in long or deep sedation. Integrated Pulmonary Index® (IPI) is an algorithm-based monitoring parameter that combines oxygenation measured by pulse oximetry (art. oxygenation, heart rate) and ventilation measured by capnography (respiratory rate, apnea > 10 s, partial pressure of end-tidal carbon dioxide [PetCO2]). The aim of this paper was to analyze the value of IPI as parameter to monitor the respiratory status in patients receiving propofol sedation during PEG-procedure. Patients reporting for PEG-placement under sedation were randomized 1:1 in either standard monitoring group (SM) or capnography monitoring group including IPI (IM). Heart rate, blood pressure and arterial oxygen saturation were monitored in SM. In IM additional monitoring was performed measuring PetCO2, respiratory rate and IPI. Capnography and IPI values were recorded for all patients but were only visible to the endoscopic team for the IM-group. IPI values range between 1 and 10 (10 = normal; 8-9 = within normal range; 7 = close to normal range, requires attention; 5-6 = requires attention and may require intervention; 3-4 = requires intervention; 1-2 requires immediate intervention). Results on capnography versus standard monitoring of the same study population was published previously. A total of 147 patients (74 in SM and 73 in IM) were included in the present study. Hypoxic events occurred in 62 patients (42%) and severe hypoxic events in 44 patients (29%), respectively. Baseline characteristics were equally distributed in both groups. IPI = 1, IPI < 7 as well as the parameters PetCO2 = 0 mmHg and apnea > 10 s had a high sensitivity for hypoxic and severe hypoxic events, respectively (IPI = 1: 81%/81% [hypoxic/severe hypoxic event], IPI < 7: 82%/88%, PetCO2: 69%/68%, apnea > 10 s: 84%/84%). All four parameters had a low specificity for both hypoxic and severe hypoxic events (IPI = 1: 13%/12%, IPI < 7: 7%/7%, PetCO2: 29%/27%, apnea > 10 s: 7%/7%). In multivariate analysis, only SM and PetCO2 = 0 mmHg were independent risk factors for hypoxia. IPI (IPI = 1 and IPI < 7) as well as the individual parameters PetCO2 = 0 mmHg and apnea > 10 s allow a fast and convenient conclusion on patients' respiratory status in a morbid patient population. Sensitivity is good for most parameters, but specificity is poor. In conclusion, IPI can be a useful metric to assess respiratory status during propofol-sedation in PEG-placement. However, IPI was not superior to PetCO2 and apnea > 10 s.

Increasing normality-persisting barriers: Current socio-demographic characteristics of 350 individuals diagnosed with gender dysphoria.

INTRODUCTION: The number of individuals requesting medical treatment for gender dysphoria has increased significantly within the past years. Our purpose was to examine current biographic and socio-demographic characteristics and aspects of legal gender reassignment. DESIGN: Medical files from n = 350 individuals of a German Endocrine outpatient clinic were collected from 2009 to 2017 and analysed retrospectively. RESULTS: Ratio of transwomen to transmen equates to 1:1.89 with a remarkable increase of transmen by the year 2013, showing a reversal of gender distribution compared with previous studies for the first time. Use of illegal substances or self-initiated hormone therapy was rare (4.6 and 2.1%). Satisfaction with gender-affirming hormone therapy was significantly higher in transmen than in transwomen (100% vs 96.2%, P = .005). Use of antidepressants declined significantly after onset of hormone treatment in transmen (13% vs 7%; P = .007). The number of individuals with a graduation diploma was only about half as high as in the general population (14.3% vs 27.3%), whereas unemployment rate was more than twice as high (14% vs 6.9%). Median latency between application for legal gender reassignment and definitive court decision was 9 months. CONCLUSIONS: Our data provide possible indications for a decline of psychosocial burden in individuals diagnosed with gender dysphoria over the last years. However, affected individuals are still limited in their occupational and financial opportunities as well as by a complex and expensive procedure of legal gender reassignment in Germany.

Capnography monitoring of non-anesthesiologist provided sedation during percutaneous endoscopic gastrostomy placement: A prospective, controlled, randomized trial.

BACKGROUND AND AIM: A number of studies were able to show a reduction of hypoxemia episodes during procedural sedation through the use of capnography (CA). The present study investigates the number of episodes of hypoxemia during percutaneous endoscopic gastrostomy (PEG) placement with propofol sedation comparing standard monitoring (SM) versus SM with additional CA surveillance. METHODS: In this single center randomized controlled trial, 150 patients were prospectively randomized 1:1 in either the SM group or the CA group after stratification for ASA class, PEG method (push or pull method), presence of head and neck tumor, and tracheostomy. CA analysis was performed for all patients but was blinded for the endoscopic team in the SM group. RESULTS: In the SM group, 57% episodes of hypoxemia (SpO2  < 90% for > 15 s) and 41% episodes of severe hypoxemia (SpO2  < 85% for > 15 s) were observed in comparison with 28% and 20% in the CA group, respectively. Odds ratios for hypoxemia and severe hypoxemia were 0.29 (confidence interval 0.15-0.57; P = 0.0005) and 0.35 (confidence interval 0.17-0.73; P = 0.008) in favor of the CA group. On average, CA was able to detect imminent mild and severe hypoxemia 83 and 99 s before standard monitoring. Standard monitoring represented an independent risk factor for hypoxemia and severe hypoxemia. CONCLUSIONS: Respiratory complications of sedation during PEG placement are frequent events. CA is able to detect imminent hypoxemia at an early time point. This allows an early intervention and consecutively the avoidance of mild and severe hypoxemia. Therefore, CA monitoring can be recommended particularly during PEG insertion procedures.

[Management of hemostasis in gastroenterology critical care]. / Gerinnungsmanagement in der gastroenterologischen Akut- und Intensivmedizin.

In emergency medicine and intensive care the key to control active bleeding - besides definitive therapy (endoscopy, therapeutic angiography or operation) - often is to improve the patients clotting and thrombus formation. Knowledge about routine laboratory testing, their strength and weaknesses as well as indications and dosing of pro-coagulants and blood products remains pivotal in these situations. Achieving hemostasis can be especially challenging in patients with liver cirrhosis, innate or acquired coagulation disorders. This review summarizes the principles of hemostasis diagnostics and management in acute bleeding for gastroenterologists and hepatologists including novel available antidotes and innovative tools for patients with advanced liver disease such as thromboelastometry.

Prolonged retention of prophylactic pancreatic stents is not associated with increased complications.

OBJECTIVES: The risk of post-ERCP pancreatitis (PEP) can be reduced effectively by the placement of a self dislodging pancreatic stent. The present study analyzed whether a prolonged interval until stent passage evaluation and removal of retained stents is associated with an increased risk for clinically relevant complications. METHODS: In the retrospective study 182 patients receiving a pancreatic stent for PEP prophylaxis were included and clinical data and complications until documented spontaneous stent dislodgement or removal were analyzed. RESULTS: The main indication for ERCP was choledocholithiasis (40.1%) followed by malignant stenosis (30.8%). Stent passage evaluation was performed in 34.1% at day 1-4, 23.6% at day 5-10, 17.6% at day 11-28 and 24.7% at day >28. PEP occurred in 13.1% of patients with no case of severe PEP. No association between PEP and day of stent passage evaluation (p = 0.719), retention of the pancreatic stent at time of evaluation (0.867) or prolonged stent retention >10 days (0.234) was observed. Only the duration of the procedure was associated with risk for PEP (p = 0.037). Besides PEP only one clinically relevant complication was observed in the cohort (0.5%) which was a late possibly stent related pancreatitis at day 9 after the procedure that resolved completely. CONCLUSIONS: A prolonged interval for stent passage evaluation and stent retention is not associated with an increase of clinically relevant complications. A later evaluation and extraction of retained stents might be acceptable in selected cases where an additional endoscopic procedure can be saved due to a planned follow-up endoscopy.

Diagnostic Yield and Outcomes of Computed Tomography of the Head in Critically Ill Nontrauma Patients.

BACKGROUND: Computed tomography of the head (HCT) is a widely used diagnostic tool, especially for emergency and trauma patients. However, the diagnostic yield and outcomes of HCT for patients on medical intensive care units (MICUs) are largely unknown. METHODS: We retrospectively evaluated all head CTs from patients admitted to a single-center MICU during a 5-year period for CT indications, diagnostic yield, and therapeutic consequences. Uni- and multivariate analyses for the evaluation of risk factors for positive head CT were conducted. RESULTS: Six hundred ninety (18.8%) of all patients during a 5-year period underwent HCT; 78.7% had negative CT results, while 21.3% of all patients had at least 1 new pathological finding. The main indication for acquiring CT scan of the head was an altered mental state (AMS) in 23.5%, followed by a new focal neurology in 20.7% and an inadequate wake up after stopping sedation in 14.9% of all patients. The most common new finding was intracerebral bleeding in 6.4%. In 6.7%, the CT scan itself led to a change of therapy of any kind. Admission after resuscitation or a new focal neurology were independent predictors of a positive CT. Psychic alteration and AMS were both independent predictors of a higher chance of a negative head CT. Positive HCT during MICU is an independent predictor of lower survival. CONCLUSIONS: New onset of focal neurologic deficit seems to be a good predictor for a positive CT, while AMS and psychic alterations seem to be very poor predictors. A positive head CT is an independent predictor of death for MICU patients.

Prophylactic percutaneous endoscopic gastrostomy in patients with head and neck cancer: Influence on nutritional status, utilisation rate and complications.

BACKGROUND: Patients with head and neck cancer (HNC) are at high risk for malnutrition because of tumour localisation and therapy. Prophylactic percutaneous endoscopic gastrostomy (PEG) tube placement is common practice to prevent malnutrition. OBJECTIVE: To investigate the benefits of prophylactic PEG tube placement for HNC patients in terms of the influence on patients' nutritional status, utilisation rate, complications and to identify the predictors of PEG tube utilisation. METHODS: All consecutive HNC patients who underwent prophylactic PEG tube insertion between 1 January 2011 and 31 December 2012 prior to therapy were enrolled. The PEG tube utilisation rate, complications, the patients' nutritional status and tumour therapy were evaluated with the help of electronic patient charts and telephone interviews. RESULTS: A total of 181 patients (48 female, median 67.5 years) were included. The PEG utilisation rate in the entire cohort was 91.7%. One hundred and forty-nine patients (82.3%) used the PEG tube for total enteral nutrition, 17 patients (9.4%) for supplemental nutrition and 15 patients (8.3%) made no use of the PEG tube. Peristomal wound infections were the most common complications (40.3%) in this study. A high Nutritional Risk Screening (NRS) score prior to tube insertion was found to be independently associated with PEG utilisation. No significant weight changes were observed across the three patient subgroups. CONCLUSIONS: The overall PEG tube utilisation rate was high in this study. However, given the high rate of infections, diligent patient selection is crucial in order to determine which patients benefit most from prophylactic PEG tube insertion.

The EFSUMB Guidelines and Recommendations for the Clinical Practice of Elastography in Non-Hepatic Applications: Update 2018.

This manuscript describes the use of ultrasound elastography, with the exception of liver applications, and represents an update of the 2013 EFSUMB (European Federation of Societies for Ultrasound in Medicine and Biology) Guidelines and Recommendations on the clinical use of elastography.

[Thyroid Elastography]. / Schilddrüsen-Elastografie.

Thyroid nodules are a common finding especially in regions with inadequate iodine supply. Ultrasound is an accurate method for the detection of thyroid nodules, but it has a low accuracy for the differentiation between benign and malignant thyroid nodules. Therefore, in patients with normal thyroid stimulating hormone fine-needle-aspiration-biopsy (FNAB) is presently recommended as supplementary diagnostic methods in the evaluation of thyroid nodules. However, a relevant number of patients with the final diagnosis of benign thyroid nodules receive thyroid surgery more for diagnostic than for therapeutic purposes. A classical criterion of malignancy is a hard or firm consistency upon palpation or ultrasound-probe pressure. Previously this attribute was subjective and dependent on the experience of the examiner. With the introduction ultrasound-based elastography a reproducible qualitative assessment of tissue consistency became available. The aim of the present article is to provide an update of the literature on different available techniques and the results reported both for thyroid nodules differentiation and for diffuse thyroid disease evaluation. Advantages and limitations of elastography are also discussed.

Multispecies blow fly myiasis combined with hypothermia in a man assumed to be dead.

We describe the case of a man who was found with severe hypothermia and advanced myiasis involving five species of blow flies, which eventually led to a transtibial amputation of the man's right leg. A case of such a heavy and species-rich infestation with fly larvae in an urban environment is extraordinary and has, to our knowledge, never been described so far. Best practice in cases such as this one demands accurate species identification not only to ensure appropriate treatment and pest management but also, from a forensic point of view, to explore the possibility of third-party responsibility. The cooperation between physicians and forensic entomologists is highlighted.

Ultrasound of Thyroid Nodules.

Thyroid nodules are a common finding in the general population. Ultrasonography is the most sensitive imaging tool for diagnosing thyroid nodules. However, sonographic differentiation of hormonally active versus inactive nodules, and in particular benign versus malignant nodules, remains unreliable. In this context, thyroid scintigraphy has its clinical significance predominantly in diagnosing hormonal activity of thyroid nodules. However, most nodules are benign and a significant number of patients undergo surgery for diagnostic rather than for therapeutic reasons. Efforts of the past years aimed to improve sonographic risk stratification, to predict malignancy of thyroid nodules through standardized diagnostic assessment of validated risk factors, in order to select patients who require further diagnostic workup. In the last years, several imaging and reporting systems, giving standardized categories with rates of malignancy, were evaluated as a basis for further clinical management. Recent technological developments, such as elastography, also show promising data and might be implemented into clinical practice. Ultrasound-guided fine needle aspiration is the key element in the diagnosis of sonographically suspicious thyroid nodules and significantly contributes to the diagnosis of malignancy versus benignity.

No Distal Migration in Unfixed Versus Fixed Cell Structure Covered Self-Expanding Metal Stents for Treatment of Benign Biliary Disease.

BACKGROUND: Fully covered self-expandable metal stents (FCSEMS) are increasingly used for treatment of benign common bile duct (CBD) stricture or leakage, but dislodgement of FCSEMS is frequent. AIMS: To compare dislocation rate and clinical outcome of a standard fixed cell structure FCSEMS (S-FCSEMS) to a novel FCSEMS with an unfixed cell structure (N-FCSEMS). METHODS: We performed a retrospective analysis of all patients with FCSEMS insertion for benign biliary disease at our Hospital from 03/2008 to 03/2014. Both stent types N-FCSEMS and S-FCSEMS were applied as available unrelated to the indication. RESULTS: Twenty-nine patients (S-FCSEMS: 18, N-FCSEMS: 11) were included. Stent placement was technically successful in 28/29 (96.6 %) patients; stent removal was successful in 26/27 (96.2 %). Two patients with N-FCSEMS were excluded due to unsuccessful placement and withdrawal of consent for stent removal, respectively. Stent migration into the duodenum (distal migration) was observed in 9/18 (50 %) in the S-FCSEMS group compared to 0/9 in the N-FCSEMS (p < 0.005). FCSEMS migration into the CBD (proximal migration) was found in 2/18 (11 %, S-FCSEMS) versus 2/9 (22 %, N-FCSEMS, p = 0.514). A foreshortening of the N-FCSEMS occurred in 3/9 patients (33 %) compared to 0/18 S-FCSEMS (p = 0.08). Clinical resolution of the treated CBD-disease was observed in 5/9 (56 %, N-FCSEMS) versus 12/18 (67 %, S-FCSEMS) at the time of stent removal (p = 0.604) and in 0/9 and 10/18 (56 %) cases during follow-up, respectively (p < 0.005). CONCLUSION: An unfixed cell structure of FCSEMS seems to prevent distal migration, but proximal migration still occurs and foreshortening of the N-FCSEMS constrains clinical outcome.

Low vitamin D serum concentration is associated with high levels of hepatitis B virus replication in chronically infected patients.

UNLABELLED: Vitamin D is an important immune modulator that plays an emerging role in inflammatory and metabolic liver diseases, including infection with hepatitis C virus (HCV). In contrast, the relationship between vitamin D metabolism and chronic hepatitis B (CHB) is less well characterized. Therefore, we quantified 25(OH)D3 serum levels in a cohort of 203 treatment-naïve patients with chronic hepatitis B virus (HBV) infection and tested for their association with clinical parameters of CHB. Of 203 patients, 69 (34%), 95 (47%), and 39 (19%) had severe vitamin D deficiency (25(OH)D3 <10 ng/mL), vitamin D insufficiency (25(OH)D3 ≥10 and <20 ng/mL), or adequate vitamin D serum levels (25(OH)D3 ≥20 ng/mL), respectively. In both uni- and multivariate analyses, HBV DNA viral load (log10 IU/mL) was a strong predictor of low 25(OH)D3 serum levels (P = 0.0007 and P = 0.000048, respectively) and vice versa. Mean 25(OH)D3 serum concentrations in patients with HBV DNA <2,000 versus ≥2,000 IU/mL were 17 versus 11 ng/mL, respectively (P < 0.00001). In addition, hepatitis B early antigen (HBeAg)-positive patients had lower 25(OH)D3 serum levels than HBeAg-negative patients (P = 0.0013). Finally, 25(OH)D3 and HBV DNA serum levels showed inverse seasonal fluctuations. CONCLUSION: Low 25(OH)D3 serum levels are associated with high levels of HBV replication in patients with CHB. This represents a major difference from chronic hepatitis C, where numerous previous studies have shown a lack of correlation between HCV viral load and vitamin D serum levels. Inverse seasonal fluctuations of 25(OH)D3 and HBV DNA serum levels are suggestive of a functional relationship between both variables.