Search

The article presents a study that evaluates the intrauterine course and the effects of tricuspid atresia detected in the fetus. The study is undertaken through a review of all tricuspid atresia cases identified prenatally between 1998 and 2006 in three referral centers in Germany. Results of the study show that tricuspid atresia were detected in 54 cases during the study period, 28 cases exhibit concordant ventriculoarterial connection of which 14 had aortic outflow obstruction.

We reviewed the natural history and assessed the SMN2 copy number of 66 patients with infantile spinal muscular atrophy (SMA) type I born between 2000 and 2005 in Germany whose diagnosis was confirmed by a homozygous SMN1 deletion in the first 6 months of life. After excluding patients who had received valproic acid, the median/mean age at disease endpoint was 6.1/7.3 months (range 0.0–34.0). Four (6.1%) patients with one SMN2 copy had severe SMA type ‘0’ with joint contractures and respiratory distress from birth. Median/mean age at onset (months) in 57 (86.3%) patients with two SMN2 copies was 1.2/1.3, and 3.5/3.4 in 5 (7.6%) patients with three SMN2 copies. Median/mean age at disease endpoint was 6.5/7.8 months (range 0.5–30) in patients with two SMN2 copies. All patients with three SMN2 copies were still alive at 10–55 months, two of them under permanent ventilation. Our data are relevant for prognostication and genetic counselling. The observed clinical variability, especially in the group with two SMN2 copies, might be important for clinical trials in SMA I where a possible control group could be defined as follows: age at onset within 4–5 months, age at genetic diagnosis <6 months, two SMN2 copies present, head control in less than 10%, no respiratory distress from birth, disease endpoint either age at death or age at permanent ventilation. [ABSTRACT FROM AUTHOR]

The article presents a study which aims to evaluate the scope of fetal cardiac defects associated with abnormal sonographic findings in the area behind the heart (ABTH) in the four-chamber view. The study included a retrospective review of 393 fetuses with congenital heart defects detected in 2003 to 2005 at a tertiary referral center in Bonn, Germany. In conclusion, the ABTH in the four-chamber view is easy to evaluate and offers important diagnostic markers for fetal congenital heart defects.

The article discusses the findings on evaluating the prevalence of anti-hepatitis D virus-immunoglobulin G (HDV-IgG) for hepatitis B surface antigen (HBsAg)-positive outpatients in Germany. It mentions that the overall seroprevalence for anti-HDV-IgG was 6.8% in 28 male patients wherein 18 were HDV-IgG positive out of 254. It notes that the prevalence of chronic hepatitis B may be as high as 0.6% in the country wherein HBV vaccination and regular screening is the best way to earlier detection.

Objectives. This summary evaluates the outcomes of orthotopic liver transplantation (OLT) of HIV-positive patients in Germany. Methods. Retrospective chart analysis of HIV-positive patients, who had been liver-transplanted in Germany between July 1997 and July 2011. Results. 38 transplantations were performed in 32 patients at 9 German transplant centres. The reasons for OLT were end-stage liver disease (ESLD) and/or liver failure due to hepatitis C (HCV) (n = 19), hepatitis B (HBV) (n = 10), multiple viral infections of the liver (n = 2) and Budd-Chiari-Syndrome. In July 2011 19/32 (60%) of the transplanted patients were still alive with a median survival of 61 months (IQR (interquartile range): 41-86 months). 6 patients had died in the early posttransplantation period from septicaemia (n = 4), primary graft dysfunction (n = 1), and intrathoracal hemorrhage (n = 1). Later on 7 patients had died from septicaemia (n = 2), delayed graft failure (n = 2), recurrent HCC (n = 2), and renal failure (n = 1). Recurrent HBV infection was efficiently prevented in 11/12 patients; HCV reinfection occurred in all patients and contributed considerably to the overall mortality. Conclusions. Overall OLT is a feasible approach in HIV-infected patients with acceptable survival rates in Germany. Reinfection with HCV still remains a major clinical challenge in HIV/HCV coinfection after OLT. [ABSTRACT FROM AUTHOR]

Real-world data on the management of patients with primary biliary cholangitis (PBC) are so far scarce in Germany. Therefore, we aimed to establish a nationwide registry and describe the clinical characteristics and therapy of PBC patients.Three different cohorts defined as ursodeoxycholic acid (UDCA) responders, as inadequate responders according to Paris II criteria, and as newly diagnosed patients were prospectively recruited.This manuscript includes the baseline data of the project.In total, 33/77 (43%) contacted centres (58% of university hospitals, 38% of non-university hospitals, and 24% of private practices) recruited 515 patients including 204 UDCA responders, 221 inadequate responders to UDCA, and 90 newly diagnosed patients.All patients were treated with UDCA; however, a UDCA dosage below the recommended dosage of 13 mg/kg/d was observed in 38.5% of individuals after 12 months of treatment. UDCA dosages were lower in nonacademic compared to academic centres.Only 75/219 (38.5%) of inadequate responders to UDCA received a second-line therapy with obeticholic acid (OCA) and/or bezafibrate (BZF). OCA (13% vs. 4.5%) and BZF (14% vs. 6.5%) were significantly more often prescribed by academic vs. nonacademic centres.Pruritus (27% vs. 15.5%), fatigue (23% vs. 4.5%), and sicca syndrome (14% vs. 1%) were significantly more often reported by academic centres.The German PBC registry could be established, which indicates suboptimal therapy in a relevant proportion of patients and shows significant differences between academic and nonacademic centres. Results are fundamental to improving clinical management at different levels of care., Competing Interests: JW: Lecturer and advisory board member for Intercept/Advanz Pharma, GSK, Ipsen TM: Ssupported by the German Research Foundation Grants MU 2864/1-3 and MU 2864/3- 1.KS: Receipt of speaker´s honoraria or advisory board: Gilead, Intercept/Advanz Pharma, Abbvie, Falk, Novo Nordisk HB: Consultant: Intercept/Advance Pharma, Ipsen GD: Consultant / speaker: AbbVie, Advanz/Intercept, Alexion, Falk Foundation, Gilead, Novartis, Orphalan, Univar PAR: Consulting and lectures fees: Astra Zeneca, BMS, Boston Scientific, CSL Behring, Gilead, Pfizer, Abbvie, Norgine JMS: Consultant: Astra Zeneca, Apollo Endosurgery, Bayer, Boehringer Ingelheim, BMS, Gilead Sciences, GSK, Intercept Pharmaceuticals, Ipsen, Inventiva Pharma, Madrigal, MSD, Northsea Therapeutics, Novartis, Novo Nordisk, Pfizer, Roche, Sanofi, Siemens Healthineers. Research Funding: Gilead Sciences, Boehringer Ingelheim, Siemens Healthcare GmbH. Stock Options: AGED diagnostics, Hepta Bio. Speaker Honorarium: Boehringer Ingelheim, Echosens, MedPublico GmbH, Novo Nordisk, Madrigal Pharmaceuticals, Histoindex, MedPublico GmbH SZ: Speakers bureau and/or consultancy: Abbvie, BioMarin, Boehringer Ingelheim, Gilead, GSK, Intercept, Ipsen, Janssen, Madrigal, MSD/Merck, NovoNordisk, SoBi, Theratechnologies KGS: Consultant: Advance Pharma, Speaker Honorarium: AbbVie, GileadJT has received speaking and/or consulting fees from Versantis, Gore, Boehringer-Ingelheim, Falk, Grifols, Genfit and CSL Behring. WPH: Consultant or Speaker Honorarium: Intercept /Advanz, Ipsen, NovoNordisk, Gilead, Abbvie, Norgine CS: Consultant, Study support or Speaker Honorarium: Calliditas, Falk, Intercept/Advanz, Ipsen, Mirum ER: Receipt of honoraria or consultation fees/advisory board: Abbvie, Amgen, Intercept, Medac, Merz, Norgine, Falk Foundation, Gilead, Pfizer, Repha, Takeda AEK: Research grant: Intercept. Speakers bureau: Abbvie, Advanz, AOP Orphan, Bayer, BMS, CMS, CymaBay, Falk, Gilead, GSK, Intercept, Ipsen, Newbridge, Novartis, Lilly, Mirum, MSD, Roche, Zambon. Consultant: Abbvie, Advanz, Alentis, AlphaSigma, AstraZenca, Avior, Bayer, BioNTech, CymaBay, Eisai, Escient, Falk, FMC, Gilead, GSK, Guidepoint, Intercept, Ipsen, Mirum, Medscape, MSD, Myr, Roche, Takeda, Viofor MR: Consultant, or Speaker Honorarium: Intercept/Advanz, Gilead, Abbvie AT: Speaker Honorarium: Intercept/Advanz VK: Consultant Astra Zeneca, Speaker’s Honoraria from AbbVie, Gilead, Falk, Mirum, Albireo/Ipsen, Merck, MedUpdate GmbH, Sanofi, CSL Behring ER: Receipt of honoraria or consultation fees/advisory board: Abbvie, Amgen, Intercept, Medac, Merz, Norgine, Falk Foundation, Gilead, Pfizer, Repha, Takeda FT: Research grant: Allergan, BMS, Inventiva, Gilead. Speakers bureau: Gilead, Abbvie, Falk, Merz, Orphalan, Advanz. Consultant: Allergan, AstraZeneca, Gilead, Abbvie, Alnylam, BMS, Intercept / Advanz, Inventiva, Pfizer, Novartis, Novo Nordisk, Sanofi. CT: Receipt of honoraria or consultation fees/advisory board: Intercept/Advanz Pharma TB: Receipt of grants/research supports: Abbvie, BMS, Gilead, MSD/Merck, Humedics, Intercept, Merz, Norgine, Novartis, Orphalan, Sequana Medical; Receipt of honoraria or consultation fees/advisory board: Abbvie, Alexion, Albireo, Bayer, Gilead, GSK, Eisai, Enyo Pharma, HepaRegeniX GmbH, Humedics, Intercept, Ipsen, Janssen, MSD/Merck, Novartis, Orphalan, Roche, Sequana Medical, SIRTEX, SOBI, and Shionogi; Participation in a company sponsored speaker’s bureau: Abbvie, Advance Pharma, Alexion, Albireo, Bayer, Gilead, Eisai, Falk Foundation, Intercept, Ipsen, Janssen, MedUpdate GmbH, MSD/Merck, Novartis, Orphalan, Sequana Medica, SIRTEX, and SOBI Nothing to disclose: AF, RG, UN, TB, AW, MH, RG, CB, TTW, RB, HG, ND, MM, PM, JUM, AK, KP, NKB, (Thieme. All rights reserved.)

Background: Post-COVID-19 syndrome (PCS; also known as "long COVID") is a relatively novel disease comprising physical, psychological, and cognitive complaints persisting several weeks to months after acute infection with SARS-CoV-2. Approximately 10% of patients with COVID-19 are affected by long-term symptoms. However, effective treatment strategies are lacking. The ErgoLoCo (Occupational Therapy [Ergotherapie] for Long COVID) study was designed to develop and evaluate a novel occupational therapy (OT) concept of online delivery of therapy for long COVID., Objective: The primary study objective is to assess the feasibility of the online OT intervention in PCS. Secondary aims include the evaluation of online OT concerning cognitive problems, occupational performance, and social participation., Methods: This randomized controlled interventional pilot study involves parallel mixed methods process analyses and a realist evaluation approach. A total of 80 clients with PCS aged at least 16 years will be recruited into two interventional groups. The control cohort (watch and wait) comprises 80 clients with long COVID. Treatment is provided through teletherapy (n=40) or delivery of prerecorded videos (n=40) using the same standardized OT concept twice weekly over 12 weeks. Analyses of quantitative questionnaires and qualitative interviews based on the theoretical framework of acceptability will be performed to assess feasibility. Focus group meetings will be used to assess how acceptable and helpful the intervention was to the participating occupational therapists. Standardized tests will be used to assess the initial efficacy of the intervention on neurocognitive performance; limitations in mobility, self-care, and everyday activities; pain; disabilities; quality of life (QoL); social participation; and anxiety and depression in PCS, and the possible effects of online OT on these complaints., Results: The German Ministry of Education and Research provided funding for this research in March 2022. Data collection took place from October 2022 to August 31, 2023. Data analysis will be completed by the end of April 2024. We anticipate publishing the results in the fall of 2024., Conclusions: Despite the enormous clinical need, effective and scalable treatment options for OT clients who have PCS remain scarce. The ErgoLoCo study will assess whether online-delivered OT is a feasible treatment approach in PCS. Furthermore, this study will assess the effect of the intervention on cognitive symptoms, QoL, and occupational performance and participation in everyday life. Particular emphasis will be placed on the experiences of clients and occupational therapists with digitally delivered OT. This study will pave the way for novel and effective treatment strategies in PCS., Trial Registration: German Clinical Trial Registry DRKS00029990; https://drks.de/search/de/trial/DRKS00029990., International Registered Report Identifier (irrid): PRR1-10.2196/50230., (©Christina Müllenmeister, Andrea Stoelting, Dominik Schröder, Tim Schmachtenberg, Simon Ritter, Iman El-Sayed, Sandra Steffens, Frank Klawonn, Sandra Klawitter, Stefanie Homann, Marie Mikuteit, Christoph Berg, Georg Behrens, Eva Hummers, Aisha Cook, Frank Müller, Alexandra Dopfer-Jablonka, Christine Happle. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 13.05.2024.)

Background: The carbohydrate antigen 125 (CA125) was proven as a robust biomarker for risk stratification in adults with heart failure. This is the first study analyzing CA125 in a cohort of infants with congenital diaphragmatic hernia (CDH)., Methods: Sixty-eight infants with CDH, treated at the University Children's Hospital Bonn (Germany), between January 2018 and February 2021, were prospectively enrolled for analysis. CA125 values were measured at the following timepoints: 6,12, 24, 48 h, and during ECMO daily from day 1 to day 7., Results: In infants not surviving to discharge, CA125 values were significantly higher at day 1 (6, 12, and 24 h). Infants with subsequent need for ECMO presented significantly higher CA125 values at 12 h of life. During ECMO, CA125 values measured at day 1 were significantly higher in infants not surviving to discharge. In the ROC analysis, a CA125 value of ≥10 U/ml was calculated as optimal cut-off for the prediction of ECMO and in-hospital mortality. CA125 values correlated significantly with the severity of PH and ventricular dysfunction., Conclusions: CA125 values correlate significantly with echocardiographic markers of PH and ventricular dysfunction and correlate significantly with parameters of disease severity (need for ECMO, mortality)., Impact: CA125 was proven as robust cardiac biomarker in adult cohorts. Information about the utility as a biomarker in neonatal cohorts is lacking. This is the first study analyzing CA125 as a cardiac biomarker in a cohort of infants with congenital diaphragmatic hernia (CDH). CA125 correlates significantly with markers of echocardiographic assessment (PH and ventricular dysfunction) in infants with CDH and helps to identify infants at high risk for ECMO and in-hospital mortality. The results underline the need for the inclusion of cardiac biomarkers in the clinical routine in neonates at risk for cardiopulmonary failure., (© 2022. The Author(s).)

Vegetation-plot resurvey data are a main source of information on terrestrial biodiversity change, with records reaching back more than one century. Although more and more data from re-sampled plots have been published, there is not yet a comprehensive open-access dataset available for analysis. Here, we compiled and harmonised vegetation-plot resurvey data from Germany covering almost 100 years. We show the distribution of the plot data in space, time and across habitat types of the European Nature Information System (EUNIS). In addition, we include metadata on geographic location, plot size and vegetation structure. The data allow temporal biodiversity change to be assessed at the community scale, reaching back further into the past than most comparable data yet available. They also enable tracking changes in the incidence and distribution of individual species across Germany. In summary, the data come at a level of detail that holds promise for broadening our understanding of the mechanisms and drivers behind plant diversity change over the last century., (© 2022. The Author(s).)

Background: The SARS-CoV-2 pandemic has caused an unprecedented global health crisis, with exceptionally high mortality rates in high-risk groups of affected patients. It is alarming that a steadily increasing number of clinical reports on outcomes of COVID-19 in solid organ transplant (SOT) recipients suggests a detrimental impact linked to high overall mortality. However, systematic data on SARS-CoV-2 infections in SOT recipients in Germany are still scarce., Material and Methods: We conducted a survey on SARS-CoV-2 infection status among 387 SOT recipients treated at our centre during the past 5 years - located in a severely affected region in Germany. The survey was sent out two months after the first SARS CoV-2 outbreak in our region had resulted in government-imposed lockdown measures., Results: An incidence rate of 0.4% SARS-CoV-2-positive SOT recipients was determined in our cohort, in line with reported local infection rates in the general population at this time. However, the only SARS CoV-2 infection known to us within this group of patients led to severe morbidity - resulting in prolonged mechanical ventilation, hospitalisation > 60 days and finally in irreversible loss of graft function., Conclusion: Our data demonstrate that SOT recipients are at equal risk for SARS-CoV-2 infections when compared to the general population, while SARS-CoV-2 infections in SOT recipients seem to be associated with deleterious clinical consequences., Competing Interests: Markus W. Löffler ist als National Lead und Mitglied des Dissemination Committees der internationalen COVIDSurg Collaborative an entsprechenden Studien zur chirurgischen Versorgung wesentlich beteiligt gewesen. Finanzielle Interessen bestehen dabei nicht. Die anderen Autorinnen/Autoren erklären, dass keine Interessenkonflikte bestehen., (Thieme. All rights reserved.)

Background & Aims: Based on positive results from small single center studies, granulocyte-colony stimulating factor (G-CSF) is being widely used for the treatment of patients with acute-on-chronic liver failure (ACLF). Herein, we aimed to evaluate the safety and efficacy of G-CSF in patients with ACLF., Methods: In this multicenter, prospective, controlled, open-label phase II study, 176 patients with ACLF (EASL-CLIF criteria) were randomized to receive G-CSF (5 μg/kg daily for the first 5 days and every third day thereafter until day 26) plus standard medical therapy (SMT) (n = 88) or SMT alone. The primary efficacy endpoint was 90-day transplant-free survival analyzed by Cox regression modeling. The key secondary endpoints were overall and transplant-free survival after 360 days, the development of ACLF-related complications, and the course of liver function scores during the entire observation period., Results: Patients treated with G-CSF had a 90-day transplant-free survival rate of 34.1% compared to 37.5% in the SMT group (hazard ratio [HR] 1.05; 95% CI 0.711-1.551; p = 0.805). Transplant-free and overall survival at 360 days did not differ between the 2 arms (HR 0.998; 95% CI 0.697-1.430; p = 0.992 and HR 1.058; 95% CI 0.727-1.548; p = 0.768, respectively). G-CSF did not improve liver function scores, the occurrence of infections, or survival in subgroups of patients without infections, with alcohol-related ACLF, or with ACLF defined by the APASL criteria. Sixty-one serious adverse events were reported in the G-CSF+SMT group and 57 were reported in the SMT group. In total, 7 drug-related serious adverse reactions occurred in the G-CSF group. The study was prematurely terminated due to futility after conditional power calculation., Conclusions: In contrast to previous findings, G-CSF had no significant beneficial effect on patients with ACLF in this multicenter controlled trial, which suggests that it should not be used as a standard treatment for ACLF. CLINICALTRIALS., Gov Number: NCT02669680 LAY SUMMARY: Granulocyte-colony stimulating factor was considered as a novel treatment for acute-on-chronic liver failure (ACLF). We performed the first randomized, multicenter, controlled phase II trial, which showed that G-CSF did not improve survival or other clinical endpoints in patients with ACLF. Therefore, G-CSF should not be used to treat liver disease outside clinical studies., Competing Interests: Conflict of interest CE: has on-going research collaboration with Merz Pharmaceutical and Novartis. He has received speaker fees from Novartis, Gilead and Merz Pharmaceuticals. TB: Receipt of honoraria or consultation fees or participation in a company sponsored speaker’s bureau: Abbvie, Alexion, Bayer, Gilead, Eisai, Falk Foundation, Intercept, Ipsen, Janssen, MSD/Merck, Novartis, and Sequana Medical. Receipt of grants/research supports: Abbvie, BMS, Gilead, MSD/Merck, Humedics, Intercept, Merz, Sequana Medical. MS: Receipt of honoraria or consultation fees or participation in a company sponsored speaker’s bureau: Merck Serono GmbH, Bayer AG, ERBE Elektromedizin GmbH, Amgen Inc., Johnson&Johnson Medical GmbH, ERBE Elektromedizin GmbH, Takeda Pharmaceutical Limited, Olympus K.K., Medtronic GmbH, Intuitive Surgical Inc.. JT: has received speaking and/or consulting fees from Gore, Bayer, Alexion, MSD, Gilead, Intercept, Norgine, Grifols, Versantis, and Martin Pharmaceutical. All other authors declared no conflict of interest. Please refer to the accompanying ICMJE disclosure forms for further details., (Copyright © 2021 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Objective: Evaluation of course and outcome of pregnancies with prenatally diagnosed fetal teratomas of various locations in a single center between 2002 and 2019., Methods: Retrospective observational single-center study including prenatally suspected or diagnosed fetal teratomas. Focus was put on ultrasound findings during pregnancy. Complications, need for intervention and outcomes were compared according to tumor location., Results: 79 cases of fetal teratomas were seen at our center between 2002 and 2019. Most frequent tumor locations were the sacrococcygeal region (59.5%), neck (20.2%) and oropharynx (7.6%). Complications mainly included polyhydramnios and cardiac compromise. Need for intervention during pregnancy was significantly higher in pericardial teratomas. Preterm birth before 37 and early preterm birth before 32 weeks occurred in 72.7% and 29.1%, respectively. Major causes of perinatal death were tumor bleeding in sacrococcygeal teratomas (SCTs) and respiratory failure in cervical and oropharyngeal teratomas., Conclusion: There is a high need for intervention in pregnancies complicated by fetal teratomas. Pericardiocentesis in pericardial teratomas is often inevitable to reduce the risk of intrauterine demise. Amniotic fluid drainage in associated severe polyhydramnios helps to reduce the risk of preterm birth, a major cause of additional morbidity and mortality. MRI in supplement to prenatal ultrasound is useful in fetal teratomas of the neck and oropharynx in order to plan delivery., (© 2020 The Authors. Prenatal Diagnosis published by John Wiley & Sons Ltd.)

Objective To assess the spectrum of associated anomalies, the intrauterine course, postnatal outcome and management of fetuses with double outlet right ventricle (DORV). Methods All cases of DORV diagnosed prenatally over a period of 8 years were retrospectively collected in a single tertiary referral center. All additional prenatal findings were assessed and correlated with the outcome. The accuracy of prenatal diagnosis was assessed. Results Forty-six cases of DORV were diagnosed prenatally. The mean gestational age at first diagnosis was 21+4 weeks (range, 13-37). A correct prenatal diagnosis of DORV was made in 96.3% of the cases. If the relation of the great arteries, the position of the ventricular septal defect (VSD) and additional cardiac anomalies are taken into account, the prenatal diagnosis was correct in 92.6% of the cases. One case was postnatally classified as transposition of the great arteries with subpulmonary VSD and was excluded from further analysis. A total of 41 (91.1%) fetuses with DORV had major additional cardiac anomalies, 30 (66.7%) had extracardiac anomalies and 13 (28.9%) had chromosomal or syndromal anomalies. Due to their complex additional anomalies, five (11.1%) of our 45 fetuses had multiple malformations and were highly suspicious for non-chromosomal genetic syndromes, although molecular diagnosis could not be provided. Disorders of laterality occurred in 10 (22.2%) fetuses. There were 17 terminations of pregnancy (37.8%), two (4.4%) intrauterine and seven (15.6%) postnatal deaths. Nineteen of 22 (86.4%) live-born children with an intention to treat were alive at last follow-up. The mean follow-up among survivors was 32 months (range, 2-72). Of 21 children who had already undergone postnatal surgery, eight (38.1%) achieved biventricular repair and 13 (61.9%) received univentricular palliation. One recently born child is still waiting for surgery. All children predicted prenatally to need a single ventricle palliation, and all children predicted to achieve biventricular repair, ultimately received the predicted type of surgery. After surgery, 14 of 18 (77.8%) children were healthy without any impairment. Conclusion DORV is a rare and often complex cardiac anomaly that can be diagnosed prenatally with high precision. DORV is frequently associated with major additional anomalies, leading to a high intrauterine and postnatal loss rate due to terminations or declined postnatal therapy. Without additional anomalies, the prognosis is good, although approximately 60% of children will have single ventricle palliation.

Background: Hydrocolpos and hydrometrocolpos are rare malformations caused by accumulation of secretion due to congenital obstruction of the vagina. Hydro(metro)colpos may be isolated or can be combined with other malformations as part of a syndromic disorder. We report on a series of 20 cases with hydro(metro)colpos diagnosed prenatally, delineate the differential diagnoses, and illustrate the spectrum of associated malformations., Subjects and Methods: This was a retrospective study involving 20 fetuses with hydro(metro)colpos at two large tertiary referral centers in Germany over an 18-year period (2000-2017)., Results: The median diagnosis was made at 30+4 weeks of gestation, the earliest at 20+6 weeks, the latest at 37+2 weeks. All 20 fetuses presented with the typical cystic structure behind the fetal bladder. Additional malformations included urogenital malformations, hexadactyly, and heart defects. Postnatal follow-up revealed that hydro(metro)colpos was associated with anorectal malformation in 11/20 fetuses, McKusick-Kaufman syndrome or Bardet-Biedl syndrome in 4/20 fe tuses, Mayer-Rokitansky-Küster-Hauser syndrome in 3/20 fetuses, and Herlyn-Werner-Wunderlich syndrome in 1/20. In 1 fetus pressure from an intraabdominal teratoma resulted in prenatal hydro(metro)colpos., Conclusion: Hydro(me tro)colpos is a rare prenatal sonographic feature. Multidisciplinary prenatal counseling should include all potential syndromes that can present with hydro(metro)colpos in the prenatal setting., (© 2018 S. Karger AG, Basel.)

Purpose  To assess the spectrum of associated anomalies, the intrauterine course, the outcome and possible prognostic markers in prenatally diagnosed Ebstein's anomaly (EA). Materials and Methods  All cases of EA diagnosed over a period of 13 years with a minimum follow-up of 1 year were retrospectively collected in 4 tertiary referral centers in Germany. Results  In the study period 76 cases of EA were prenatally diagnosed. The mean gestational age at diagnosis was 25.0 weeks (range: 13 - 35). 41 (53.9 %) cases were isolated and 35 (46.1 %) had other cardiac and/or extracardiac anomalies. 19 (25.0 %) pregnant women opted for termination of pregnancy, intrauterine fetal death occurred in 7 cases (9.2 %), neonatal death in 14 cases (18.4 %), death in infancy or childhood in 9 cases (11.8 %) and 27 children (35.5 %) were alive at the last follow-up. After exclusion of terminations, the only parameter inversely correlated with intrauterine survival was hydrops fetalis. Prognostic parameters significantly associated with postnatal non-survival were an abnormal Celermajer index (right atrium/heart ratio > 0.7), cardiomegaly (cardiothoracic circumference ratio > 0.5), absence of antegrade flow over the pulmonary valve and earlier diagnosis in pregnancy. Conclusion  Prenatally diagnosed EA has a high morbidity and mortality with the highest loss rate in the intrauterine and neonatal period. In our study, hydrops fetalis was the only parameter significantly associated with intrauterine demise, while other prenatal markers were only significantly associated with postnatal mortality., Competing Interests: Disclosure The authors report no conflicts of interest in this work., (© Georg Thieme Verlag KG Stuttgart · New York.)

Objective: Endoscopic extraperitoneal radical prostatectomy (EERPE) and robot-assisted laparoscopic prostatectomy (RALP) are minimally invasive surgical techniques to treat localized prostate cancer. We report the outcome and complications of these two techniques conducted by one individual surgeon., Patients and Methods: 86 patients underwent EERPE between January 2008 and June 2011, and 100 patients underwent RALP between August 2011 and October 2012. All surgeries were performed by one single surgeon., Results: The patients of the EERPE and RALP groups had similar clinical characteristics in PSA, prostate volume and D'Amico classification, and were significantly different in their age and BMI as well as in the number of prior surgeries. RALP surgeries were significantly slower (183 vs. 157 min) but also involved lower blood loss (147 vs. 245 ml). Pathological stages and positive surgical margins were similar in both groups. Complications were assessed by the Clavien-Dindo classification. 6 patients in the EERPE group and 3 patients of the RALP group suffered major complications (IIIb-IV)., Conclusion: Altogether our results indicate that the learning curve for RALP was short after experience with EERPE. We hypothesize that this is more a result of the surgical experience of the surgeon with the EERPE than on the robotic technique., (© 2015 S. Karger AG, Basel.)

Context: Familial and sporadic GH-secreting pituitary adenomas are associated with mutations in the aryl hydrocarbon receptor-interacting protein (AIP) gene. Patients with an AIP mutation (AIPmut) tend to have more aggressive tumors occurring at a younger age., Objective: The objective of the study was to investigate the frequency of AIPmut in patients diagnosed at 30 years of age or younger., Design: The German Acromegaly Registry database (1795 patients in 58 centers) was screened for patients diagnosed with acromegaly at 30 years of age or younger (329 patients). Sixteen centers participated and 91 patients consented to AIPmut analysis., Intervention: DNA was analyzed by direct sequencing and multiplex ligation dependent probe amplification Main outcome Measures: The number of patients with AIPmut was measured., Results: Five patients had either a mutation (c.490C>T, c.844C>T, and c.911G>A, three males) or gross deletions of exons 1 and 2 of the AIP gene (n = 2, one female). The overall frequency of an AIPmut was 5.5%, and 2.3% or 2.4% in patients with an apparently sporadic adenoma or macroadenoma, respectively. By contrast, three of four patients (75%) with a positive family history were tested positive for an AIPmut. Except for a positive family history, there were no significant differences between patients with and without an AIPmut., Conclusions: The frequency of AIPmut in this registry-based cohort of young patients with acromegaly is lower than previously reported. Patients with a positive family history should be tested for an AIPmut, whereas young patients without an apparent family history should be screened, depending on the individual cost to benefit ratio.

Introduction: Coronary risk factors in patients with acromegaly after first-line transsphenoidal surgery (TSS) or first-line somatostatine analogue (SSA) treatment have rarely been examined. Aim of this study was an evaluation of cardiovascular risk factors and left ventricular hypertrophy (LVH) in 3 different patient groups with treatment naïve, active (ACT), first-line medically controlled (MED) and first-line surgically treated (SUR) acromegaly and a calculation of the Framingham Weibull Risk Score (FS)., Design: Retrospective comparative matched case-control study., Patients & Methods: 40 acromegalic patients (cases aged 45-74 years, 23 men) were matched with respect to age and gender to 200 controls from the general population. 13 patients had treatment-naïve acromegaly (ACT), 12 patients were SSA treated (MED) and 15 patients were operated by TSS (SUR). Coronary risk factors were assessed after 12 months of treatment by interviews and direct laboratory measurements. Only patients normalized for IGF-I in MED and SUR group were included. FS and odds ratios (OR) from multiple conditional logistic regression (matched for age and gender, adjusted for BMI) were calculated., Results: Compared to matched controls ACT patients had higher HbA1c levels (6.9±1.4 vs. 5.5±0.7% (p<0.0001)) and an increased prevalence of left ventricular hypertrophy (LVH) (30.8 vs. 3.2% (p=0.007). MED and SUR groups were similar for gender, age, disease duration and IGF-I levels at diagnosis. Compared to matched controls, MED patients had a significantly increased diastolic blood pressure (89±9 vs. 79±11 mmHg (p=0.001), prevalence of LVH (41.7 vs. 1.7% (p<0.0001), prevalence of diabetes mellitus (33.3 vs. 10.0% (p=0.03)), higher HbA1c levels (6.8±1.3 vs. 5.5±0.7% (p=0.0005)) and a higher FS (21.2±9.7 vs. 12.4±7.7% (p=0.002), OR 1.11 [1.02-1.21] (p=0.01)) while in the SUR group only higher prevalences of LVH (40.0 vs. 4.1% (p<0.0001)) and HbA1c levels (6.4±1.2 vs. 5.5±0.8% (p=0.006)) were found compared to controls., Conclusion: When comparing treatment naive, medically treated and surgically cured patients with acromegaly to age- and gender-matched subjects from the general population, we have found an increased cardiovascular risk in patients at 12 months after first-line SSA treatment but not in patients after first-line surgery., (© Georg Thieme Verlag KG Stuttgart · New York.)

The etiology of gastroschisis remains elusive. A classic twin study was used to assess the relative contribution of environmental and genetic factors in its development. Screening of 4872 twin pregnancies identified three unreported twin pairs comprising two monozygous and one dizygous discordant pair of twins. Review of the literature identified an additional 21 twin pairs. We observed lower pair- and proband-wise concordance rates for monozygotic compared to dizygotic twin pairs, pair- and proband-wise concordance ratios below 1.0. Our results suggest environmental to play a greater role than genetic factors in the development of gastroschisis.

Background: As a minimally invasive technique endovascular aneurysm repair (EVAR) reduces the risk of mortality and should be the preferred technique used in older patients. We analysed trends in endovascular and open surgical procedures in patients hospitalized for abdominal aortic aneurysm (AAA) in Germany., Patients and Methods: We used national statistics (DRG statistics) published by the Federal Office of Statistics in Germany to calculate the incidence of patients hospitalised with ruptured (rAAA) and elective (eAAA) AAA. In addition, annual procedure rates of endovascular (EVAR) procedures were calculated., Results: Incidence rates of eAAA per 100,000 males (females) showed a small increase from 2006 to 2007 but remained almost unchanged with 74.8 (8.8) in 2007 and 74.5 (9.8) in 2009. Incidence rates of rAAA per 100 000 males remained unchanged but showed a decreasing trend in females. The rate of people treated by EVAR increased form 2006 to 2009: in males from 24.0 % to 40.3 % and in females from 17.3 % to 31.0 %. In younger males (55 - 60 years) the increase in those who received EVAR was smaller (from 22.1 % to 33.9 %) than in older males (85 - 90 years) (from 20.4 to 41.6 %). Despite a clear increase in the use of EVAR from 2006 to 2009 there is only a small trend in reduction of the death rates which is more pronounced in rAAA., Conclusions: There has been a relevant increase in EVAR procedures for the treatment of AAA in Germany in recent years. Parallel to this increase of EVAR, aneurysm-related in-hospital deaths seem be declining slightly. A causal relationship between these trends remains to be proven.

Introduction: We determined the prevalence of anterior pituitary dysfunction in a multi-centre screening program across five German endocrine centres in patients rehabilitating from TBI (GCS<13)., Patients & Methods: 246 patients (39+/-14 yrs; 133 males, 12+/-8 months after TBI) underwent a series of baseline endocrine tests with central assessment of TSH, free T4, prolactin, LH, FSH, testosterone (m), estradiol (f), cortisol, GH, and IGF-I. If IGF-I was <-2 SDS dynamic testing was performed. GHD was defined according to BMI-dependent cut-off values for GH response to GHRH+arginine of <4.2, <8.0 and <11.5 ng/ml in obese, overweight and lean subjects, respectively, or <3 micro g/l in ITT. Hypocortisolism was suggested when basal cortisol was <200 nmol/l and confirmed by ITT (peak<500 nmol/l)., Results: In TBI patients some degree of impaired pituitary function was shown in 21% (n=52/246). Total, multiple and isolated deficits were present in 1%, 2% and 18%, respectively. 19% had an IGF-I of <-1 SDS, 9% of <-2 SDS. In 5% GHD was confirmed. 9% had hypogonadism. 4% had hypocortisolism and 1% of patients had confirmed ACTH-deficiency. 12% had TSH-deficiency., Summary: In summary, in this large series carried out on an unselected group of TBI survivors we have found hypopituitarism in every fifth patient with predominantly secondary hypogonadism and hypothyreosis. Regarding somatotrope insufficiency IGF-I is decreased in 50% of GHD patients., Conclusion: These findings strongly suggest that patients who suffer head trauma should routinely undergo endocrine evaluation., (J. A. Barth Verlag in Georg Thieme Verlag KG Stuttgart. New York.)

Mosses represent ecological niches that harbor a hitherto largely uncharacterized microbial diversity. To investigate which factors affect the biodiversity of bryophyte-associated bacteria, we analyzed the bacterial communities associated with two moss species, which exhibit different ecological behaviors and importance in bog ecosystems, Sphagnum magellanicum and Sphagnum fallax, from six temperate and boreal bogs in Germany and Norway. Furthermore, their surrounding plant communities were studied. Molecular analysis of bacterial communities was determined by single-strand conformation polymorphism (SSCP) analysis using eubacterial and genus-specific primers for the dominant genera Burkholderia and Serratia as well as by sequence analysis of a Burkholderia 16S rRNA gene clone library. Plant communities were analyzed by monitoring the abundance and composition of bryophyte and vascular plant species, and by determining ecological indicator values. Interestingly, we found a high degree of host specificity for associated bacterial and plant communities of both Sphagnum species independent of the geographical region. Calculation of diversity indices on the basis of SSCP gels showed that the S. fallax-associated communities displayed a statistically significant higher degree of diversity than those associated with S. magellanicum. In contrast, analyses of plant communities of Sphagnum-specific habitats resulted in a higher diversity of S. magellanicum-specific habitats for all six sites. The higher content of nutrients in the S. fallax-associated ecosystems can explain higher diversity of microorganisms.

A polyphasic taxonomic study including DNA-DNA reassociation experiments and an extensive biochemical characterization was performed on 14 Burkholderia isolates from moss gametophytes of nutrient-poor plant communities on the southern Baltic Sea coast in northern Germany. The strains were classified within two novel species, for which the names Burkholderia bryophila sp. nov. and Burkholderia megapolitana sp. nov. are proposed. The former species also includes isolates from grassland and agricultural soil collected in previous studies. Strains Burkholderia bryophila 1S18(T) (=LMG 23644(T) =CCUG 52993(T)) and Burkholderia megapolitana A3(T) (=LMG 23650(T) =CCUG 53006(T)) are the proposed type strains. They were isolated from Sphagnum rubellum and Aulacomnium palustre, respectively, growing in the 'Ribnitzer Grosses Moor' nature reserve (Mecklenburg-Pommern, Germany). All moss isolates of both novel species showed antifungal activity against phytopathogens as well as plant-growth-promoting properties.

Objective: To report on our experience with intraamniotic injection of ethacridine lactate (EL) for second trimester termination of pregnancy (TOP) and to compare its effectiveness with vaginal PGE1 in this setting., Study Design: (a) Retrospective analysis of 54 intraamniotic EL-induced TOP. (b) Matched pair analysis of 50 second trimester TOP, using intraamniotic EL in group A (n=25) and vaginal PGE1 suppositories in group B (n=25)., Main Outcome Measures: success rate, induction-delivery interval, analgesic use, drop in maternal hemoglobin, complications., Results: (a) TOP with EL alone was successful in 50 cases (93%). Mean duration from instillation to delivery was 40.5 h (range 14-58, S.D.: +/-9.0). Mean analgesic need was low. Mean drop in hemoglobin was low (1.0 g/dl, S.D.: +/-1.1). (b) The matched pair analysis revealed a significantly shorter induction-delivery interval in the vaginal PGE1 group (mean 26.9 h, range 8-80, S.D.: +/-16.8 versus 41.0 h, range 24-55, S.D.: +/-7.3, p<.05). There were no significant differences in analgesic use or drop in hemoglobin. In both groups one case of post partum hemorrhage occurred., Conclusion: Intraamniotic instillation of ethacridine lactate in second trimester TOP is safe, cheap and successful in the vast majority of cases. Disadvantages are the longer induction-delivery interval compared to modern prostaglandins and the invasive mode of application. However, by the use of EL the side effects of repeated prostaglandin application can be avoided as well as multiple vaginal examinations. Furthermore, the time of delivery can be predicted in a narrower interval.

Objective: The purpose of this study was to evaluate the accuracy of the prenatal diagnosis of left isomerism and to assess possible diagnostic and prognostic markers., Methods: We conducted a retrospective review of all previously unpublished cases of left isomerism diagnosed in the prenatal and postnatal periods in 2 tertiary referral centers in Germany over 15 years., Results: Among 34 fetuses, 31 had a correct prenatal diagnosis of left isomerism; 31 had an interruption of the inferior vena cava with azygos continuation; 22 had different types of viscerocardiac heterotaxy; 13 had heart block; and 28 had cardiac defects, with a high prevalence of atrioventricular septal defects (n = 24), right outflow tract obstruction (n = 11), double-outlet right ventricles (n = 6), and anomalous pulmonary venous return (n = 6). Among the 34 cases, 9 underwent termination of pregnancy; 2 fetuses died in utero; 5 children died in the neonatal period; and 4 children died in infancy. Only the presence of heart block and hydrops was significantly correlated with nonsurvival (P < .05). Fourteen children survived, with a mean follow-up +/- SD of 2.9 +/- 2.6 years. Three survivors underwent single-ventricle palliation, and 1 had successful biventricular repair. Three children were awaiting cardiac repair. The remaining 7 children had minor or no associated cardiac defects and were doing well., Conclusions: Prenatal diagnosis of left isomerism is feasible, with high accuracy. Important diagnostic pointers are viscerocardiac heterotaxy, complex cardiac malformations, heart block, and interruption of the inferior vena cava. The mortality in fetuses and neonates is high in the presence of heart block and hydrops, whereas the cardiac defects influence the long-term outcome.