German Registry Research Articles

Standardized histomorphological processing of peritoneal biopsies as part of the German Peritoneal Biopsy Registry (GRIP, German registry in PD)

Das Peritoneum stellt als seröse Haut, die mit ihrem viszeralen und parietalen Anteil den Bauchraum auskleidet, ein interessantes Organ dar, welches bei der sog. Peritoneal- oder Bauchfelldialyse (PD) klinische Beachtung findet. Bei diesem Nierenersatzverfahren wird die Semipermeabilität des Peritoneums genutzt, um mittels unterschiedlich osmolarer Dialyseflüssigkeiten die sog. harnpflichtigen Substanzen aus dem Körper zu eliminieren. Dies ist insbesondere bei jungen Patienten eine ideales Nierenersatzverfahren und funktioniert in der Regel zumindest einige Zeit sehr gut. Vorschäden des Peritoneums durch die Grunderkrankung der chronischen Niereninsuffizienz oder assoziierte Komorbiditäten sowie v. a. entzündliche Veränderungen während der PD führen zu einem morphologischen Umbau des Peritoneums mit der Konsequenz des Verlusts der Filtereigenschaften, sodass die PD beendet und auf ein anderes Nierenersatzverfahren gewechselt werden muss. Die Kenntnis des morphologischen Umbaus des Peritoneums sowie möglicher begünstigender Faktoren, zu denen es derzeit noch zu wenige Daten gibt, ist wichtig für die Therapie und Prognose der Patienten, die mit PD behandelt werden. Aus diesem Grund wurde vor einigen Jahren das Deutsche Peritonealbiopsieregister (GRIP, German Registry In PD) gegründet, das mittlerweile knapp 1700 Biopsate umfasst und an diesen standardisiert klinische und histomorphologische Parameter erhebt und dokumentiert.

Prognosis of Patients with Metastatic Soft Tissue Sarcoma: Advances in Recent Years

Objective: The objective of this study was to investigate the prognosis of patients with metastatic soft tissue sarcomas (STS) and to define prognostic indicators for overall survival (OS). Methods: All patients who were treated at the Sarcoma Unit at the Mannheim University Medical Center between 2010 and 2016 and who developed metastatic disease deriving from a STS were included in this retrospective analysis. OS was investigated using data from clinical records and German registry offices. Clinical and pathological characteristics were recorded and analyzed. Results: A total number of 212 patients developed metastatic disease from STS during that period. Median OS after first documentation of metastatic disease was 24 months (95% CI 21–33). 1-, 2-, and 5-year OS rates were 70.0% (95% CI 64–77), 49.9% (95% CI 43–58), and 24.8% (95% CI 19–33), respectively. In multivariate analysis, significant predictors for mortality appeared to be gender, age, location and size of the primary tumor, histology, and disease-free interval. Conclusion: Being treated in a high-volume STS reference center in Germany, patients with metastatic disease could demonstrate an increased OS compared to former analyses. These data can be used as a benchmark for upcoming studies and highlight that further research on treatment strategies in this rare disease is urgently needed.

Working conditions of healthcare workers and clients\u2019 satisfaction with care: study protocol and baseline results of a cluster-randomised workplace intervention

BackgroundIn the present investigation the study protocol and the results at baseline of a workplace intervention are reported. It is hypothesised that the reduction of the physical and psychosocial workload of healthcare workers increases 1 their self-assessed physical and mental work ability, and 2. clients’ satisfaction with care.MethodsTwo-arm, cluster-randomised trial. Outcome data on workers and clients are collected in questionnaires at baseline, and two follow-ups between 2019 and 2021. Participants of the interventions are healthcare workers of 11 healthcare providers in Germany. At baseline, the intervention arm comprised 22 clusters (n = 174 workers); the control arm, 47 clusters (n = 276). The intervention consists of interviews and workshops, in which employees propose measures aiming to reduce the physical and psychosocial load, and strengthen resources at work. The primary outcome is the workers’ physical and mental work ability. The secondary outcome is the clients’ satisfaction with care.ResultsThere was no evidence of substantial differences between trial arms at baseline concerning the outcomes. The design effect estimates for physical and mental work ability were 1.29 and 1.05, respectively. At the end of the trial, effect sizes of at least 0.30 and 0.27 at the 80% power and 5% significance levels can be attained.ConclusionsThe results suggest that the implementation of the study design has been satisfactory. The intervention is expected to provide evidence of relatively small to medium-size effects of the intervention activities on the work ability of healthcare workers and the clients’ satisfaction with care.Trial registrationRegistration trial DRKS00021138 on the German Registry of Clinical Studies (DRKS), retrospectively registered on 25 March, 2020.

DARTS Trial

DARTS Trial

Overview of multi-center registry of aortic dissection

Aortic dissection is a life-threatening cardiovascular disease. Multi-center registration databases for aortic dissection have been established in many countries. The International Registry of Acute Aortic Dissection has produced a number of research results, which had a significant impact on the diagnosis and treatment of aortic dissection worldwide. The Society for Thoracic Surgeons Adult Cardiac Surgery Database summarizes perioperative data on aortic dissection. German Registry for Acute Aortic Dissection Type A has made remarkable achievements in the neurological protection and organ perfusion of type A aortic dissection. The Nordic Consortium for Acute Type A Aortic Dissection provides guidelines for perioperative administration of aortic dissection. However, the first Registry of Aortic Dissection in China (Sino-RAD) has not reported any new aortic dissection data in the past five years, although it has proposed a number of pathogenic characteristics of Chinese people. Therefore, it is necessary to establish our own aortic dissection database.

Influence of Macitentan on the Vascular Tone and Recruitment of Finger Capillaries Under Hypobaric Hypoxia in High Altitude.

Betge, Stefan, Stefan Drinda, Thomas Neumann, Laura Bäz, Alexander Pfeil, Christian Schulze, Ralf Mrowka, Christian Jung, and Marcus Franz. Influence of macitentan on the vascular tone and recruitment of finger capillaries under hypobaric hypoxia in high altitude. High Alt Med Biol. 21:336-345, 2020. Introduction: Acute normobaric (NH) and hypobaric hypoxia (HH) has effects on the vascular tone of larger arteries and may have effects on the microcirculation. These effects may be noninvasively detectable by automated devices. A part of these effects may be mediated by endothelin (ET) and should be influenced by macitentan (MAC), a dual endothelin receptor antagonist (ERA). Methods: We used photoplethysmographic sensors, fingertip volume sensors, nailfold capillaroscopy, and laser Doppler probes at rest and after a 5-minute forearm ischemia in healthy study subjects under NH, under HH, and under HH plus a single dose of MAC. Results: NH at simulated 4000 m led to increased heart rates (HR) and pulse wave velocities (PWV) and reduced augmentation index (AIX). The values for the AIX showed a high SD and differed between the used devices. At simulated 5500 m, only baseline mean value (BMV; EndoPAT) showed a further change, indicating less filled capillaries of the fingertips. HH (2978 m) increased HR, blood pressure values, and PWV. Focusing on the microcirculation of the fingertips, HH reduced the BMV and the nailfold capillary density and the postischemic capillary recruitment. MAC had no effect on the BMV, but antagonized the effects of HH on the nailfold capillaries and led to a strongly increased postischemic diameter of the arterial limbs. Concordantly, the postischemic blood flow velocity increment, measured through ultrasound Doppler, was increased at ALT+MAC. Conclusions: The BMV may be a parameter for changes of the microcirculation of the finger tips. A single dose of MAC blocked hypoxia-induced capillary rarefaction and enhanced postischemic hyperemia of the fingertips. These results indicate the importance of ET-1 for the regulation of the microcirculation under hypoxia. The German Registry of Clinical Studies (DRKS) ID: 00005459.

Loop ileostomy versus loop colostomy as temporary deviation after anterior resection for rectal cancer.

Construction of a temporary stoma is a common adjunct to low anterior resection for rectal cancer and can be accomplished either with loop ileostomy (LI) or loop colostomy (LC) with the question of the most appropriate one still remaining controversial. The aim of this study is to compare stoma-related morbidity between the two groups. A retrospective review was conducted including 148 consecutive patients (LI: 55/LC: 93) who underwent anterior resection for rectal cancer between January 2004 and December 2018 in our department. Time interval between low anterior resection and stoma reversal was similar for both groups. Comparison between the two groups was made regarding stoma-related morbidity after stoma construction and after stoma reversal, respectively. A total number of 17 patients suffered from complications after the construction of a protective LI compared with 25 patients after the construction of a LC (LI vs LC: 17/55 (30.1%) vs 25/93 (26.9%); p = 0.59). The most common morbidity noted in both groups before stoma closure was parastomal hernia, with the difference being statistically not significant (LI vs LC: 11/55 (20%) vs 21/93 (22.6%); p = 0.84). However, patients with LI suffered from significantly more peristomal skin irritations compared with the patients with LC (LI vs LC: 5/55 (9.1%) vs 1/93 (1.1%); p = 0.027). Overall morbidity rate after stoma closure was found to be comparable in both groups (LI vs LC: 7/37 (18.9%) vs 6/64 (9.4%); p = 0.16). The most common complication after stoma reversal was wound infection (LI vs LC: 5/37 (13.5%) vs 5/64 (7.8%); p = 0.49). With the exception of a higher rate of skin irritation after LI construction, all other postoperative outcomes were found to be comparable in both study groups. Further randomized clinical trials are required to verify these findings. The study was registered in the German Registry for Clinical Trials (DRKS00020766, date of registration: 11.02.2020).

Age dependency of body mass index distribution in childhood and adolescent inpatients with anorexia nervosa with a focus on DSM-5 and ICD-11 weight criteria and severity specifiers

Both DSM-5 and ICD-11 have provided weight cut-offs and severity specifiers for the diagnosis of anorexia nervosa (AN) in childhood, adolescence and adulthood. The aims of the current study focusing on inpatients aged < 19 years were to assess (1) the relationship between age and body mass index (BMI; kg/m2), BMI-centiles, BMI-standard deviation scores (BMI-SDS) and body height-SDS at referral, (2) the percentages of patients fulfilling the DSM-5 and ICD-11 weight criteria and severity categories for AN, and (3) the validity of the AN severity specifiers via analysis of both weight related data at discharge and inpatient treatment duration. The German Registry for Anorexia Nervosa encompassed complete data sets for 469 female patients (mean age = 15.2 years; range 8.9–18.9 years) with a diagnosis of AN (n = 404) or atypical AN (n = 65), who were ascertained at 16 German child and adolescent psychiatric hospitals. BMI at referral increased up to age 15 to subsequently plateau. Approximately one tenth of all patients with AN had a BMI above the fifth centile. The ICD-11 specifier based on a BMI-centile of 0.3 for childhood and adolescent AN entailed two equally sized groups of patients. Discharge data revealed limited validity of the specifiers. Height-SDS was not correlated with age thus stunting had no impact on our data. We corroborate the evidence to use the tenth instead of the fifth BMI-centile as the weight criterion in children and adolescents. Weight criteria should not entail major diagnostic shifts during the transition from adolescence to adulthood. The severity specifiers based on BMI or BMI-centiles do not seem to have substantial clinical validity.

Risk of recurrent hepatic encephalopathy in patients with liver cirrhosis: a German registry study

Patients with hepatic encephalopathy (HE) show low quality of life, recurrent hospitalizations and an increased mortality. We aimed to assess the natural course of patients after a recent episode of overt HE and to identify risk factors for HE recurrence in Germany. Fifteen sites took part in a prospective, observational study including patients with liver cirrhosis who had been hospitalized for HE within 3 months before recruitment. Clinical data, psychometric hepatic encephalopathy score (PHES) and critical flicker frequency were assessed quarterly for 1 year. Primary endpoint was HE recurrence requiring hospitalization, all-cause-mortality was treated as a competing risk factor. From January 2014 to March 2016, a total of 115 patients were recruited. Overall 14 premature deaths were documented. For 78 subjects follow-up data were available in accordance with the protocol. After a median of 118 days, more than half of the per-protocol cohort was readmitted to hospital due to HE (N = 34) or died (N = 11). The risk for hospitalization was significantly increased in patients who had been recruited by liver transplant centers (P = 0.003), had had frequent HE relapses prior to recruitment (P = <0.0001) or an abnormal PHES result of <-4 (P = 0.044). Abnormal PHES results barely missed level of significance as an independent risk factor for re-hospitalization in a multivariable competing risk model (P = 0.093). Patients with a history of HE are at high risk for the development of recurrent overt HE demanding hospitalization. The PHES test may aid in detection, monitoring and risk stratification of recurrent HE.

Null Effect of Olfactory Training With Patients Suffering From Depressive Disorders-An Exploratory Randomized Controlled Clinical Trial.

Due to a close functional relation between brain areas processing emotion and those processing olfaction, major depression is often accompanied by reduced olfactory function. Such hyposmia can be improved by regular olfactory training (OT) over several months. As this training furthermore improves subjective well-being, we explored whether OT is a useful complementary strategy for depression treatment. A total of 102 depressive outpatients were randomly assigned to OT or a control training condition, which were performed twice a day for 16 weeks. Compliance was continuously monitored. Before and after training we measured depression severity and olfactory function. About half of the patients of both groups did not complete the training. Among the remaining patients, depression severity decreased significantly in both groups. The absence of an interaction effect indicated no selective impact of OT and the variance of depression improvement explained by OT was as little as 0.1%. The low compliance suggests that OT is not feasible for large parts of our sample of depressive outpatients, most likely due to a disease-immanent lack of motivation. In those patients who completed the training, lack of specific effects suggest that OT is not more useful then unspecific activation or attention training.Clinical Trial RegistrationThis clinical trial was registered at German Registry for Clinical Trials (DRKS), main ID: DRKS00016350, URL: http://www.drks.de/DRKS00016350.

Studying the pathophysiology of coronavirus disease 2019: a protocol for the Berlin prospective COVID-19 patient cohort (Pa-COVID-19)

PurposeSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread worldwide causing a global health emergency. Pa-COVID-19 aims to provide comprehensive data on clinical course, pathophysiology, immunology and outcome of COVID-19, to identify prognostic biomarkers, clinical scores, and therapeutic targets for improved clinical management and preventive interventions.MethodsPa-COVID-19 is a prospective observational cohort study of patients with confirmed SARS-CoV-2 infection treated at Charité - Universitätsmedizin Berlin. We collect data on epidemiology, demography, medical history, symptoms, clinical course, and pathogen testing and treatment. Systematic, serial blood sampling will allow deep molecular and immunological phenotyping, transcriptomic profiling, and comprehensive biobanking. Longitudinal data and sample collection during hospitalization will be supplemented by long-term follow-up.ResultsOutcome measures include the WHO clinical ordinal scale on day 15 and clinical, functional, and health-related quality-of-life assessments at discharge and during follow-up. We developed a scalable dataset to (i) suit national standards of care, (ii) facilitate comprehensive data collection in medical care facilities with varying resources, and (iii) allow for rapid implementation of interventional trials based on the standardized study design and data collection. We propose this scalable protocol as blueprint for harmonized data collection and deep phenotyping in COVID-19 in Germany.ConclusionWe established a basic platform for harmonized, scalable data collection, pathophysiological analysis, and deep phenotyping of COVID-19, which enables rapid generation of evidence for improved medical care and identification of candidate therapeutic and preventive strategies. The electronic database accredited for interventional trials allows fast trial implementation for candidate therapeutic agents.Trial registrationRegistered at the German registry for clinical studies (DRKS00021688)

Prediction of mortality rate in acute type A dissection: the German Registry for Acute Type A Aortic Dissection score.

The goal was to develop a scoring system to predict the 30-day mortality rate for patients undergoing surgery for acute type A aortic dissection on the basis of the German Registry for Acute Type A Aortic Dissection (GERAADA) data set and to provide a Web-based application for standard use. A total of 2537 patients enrolled in GERAADA who underwent surgery between 2006 and 2015 were analysed. Variable selection was performed using the R-package FAMoS. The robustness of the results was confirmed via the bootstrap procedure. The coefficients of the final model were used to calculate the risk score in a Web-based application. Age [odds ratio (OR) 1.018, 95% confidence interval (CI) 1.009-1.026; P < 0.001; 5-year OR: 1.093], need for catecholamines at referral (OR 1.732, 95% CI 1.340-2.232; P < 0.001), preoperative resuscitation (OR 3.051, 95% CI 2.099-4.441; P < 0.001), need for intubation before surgery (OR 1.949, 95% CI 1.465-2.585; P < 0.001), preoperative hemiparesis (OR 1.442, 95% CI 0.996-2.065; P = 0.049), coronary malperfusion (OR 1.870, 95% CI 1.386-2.509; P < 0.001), visceral malperfusion (OR 1.748, 95% CI 1.198-2.530; P = 0.003), dissection extension to the descending aorta (OR 1.443, 95% CI 1.120-1.864; P = 0.005) and previous cardiac surgery (OR 1.772, 95% CI 1.048-2.903; P = 0.027) were independent predictors of the 30-day mortality rate. The Web application based on the final model can be found at https://www.dgthg.de/de/GERAADA_Score. The GERAADA score is a simple, effective tool to predict the 30-day mortality rate for patients undergoing surgery for acute type A aortic dissection. We recommend the widespread use of this Web-based application for standard use.

Neoadjuvant chemotherapy with gemcitabine plus cisplatin followed by radical liver resection versus immediate radical liver resection alone with or without adjuvant chemotherapy in incidentally detected gallbladder carcinoma after simple cholecystectomy or in front of radical resection of BTC (ICC/ECC): A phase III study utilizing the German Registry of Incidental Gallbladder Carcinoma Platform (GR)—The AIO/CALGP/ACO-GAIN-Trial.

TPS4653 Background: Currently, complete surgical resection represents the only potentially curative treatment option for Biliary Tract Cancer (BTC) including Gallbladder Cancer (GBC). Even after curative resection, 5-year OS is only 20–40%. GBC is relatively rare, but still the fifth most common neoplasm of the digestive tract and even the most frequent cancer of the biliary system. Gallbladder carcinoma is suspected preoperatively in only 30% of all pts, while the majority of cases are discovered incidentally by the pathologist after cholecystectomy for a benign indication. For improving curative rates in BTC and GBC, early systemic therapy combined with radical resection seems to be a promising approach. The earliest moment to apply chemotherapy would be in front of radical surgery. Encouraging results of neoadjuvant/perioperative concepts in other malignancies provide an additional rationale to use this treatment in the early phase of GBC management and even in intrahepatic and extrahepatic cholangiocarcinoma. Especially because data regarding pure adjuvant chemotherapy in BTC`s are conflicting. Methods: This is a multicenter, randomized, controlled, open-label phase III study including pts with incidentally discovered GBCs after simple cholecystectomy in front of radical liver resection and pts with resectable/borderline resectable cholangiocarcinomas (ICC/ECC) scheduled to receive perioperative chemotherapy (Gemcitabine + Cisplatin 3 cycles pre- and post-surgery) or surgery alone followed by a therapy of investigator’s choice. Primary endpoint is OS; secondary endpoints are PFS, R0-resection rate, toxicity, perioperative morbidity, mortality and QoL. A total of N=333 patients with GBC or BTC will be included. Recruitment has just started; first patient in was on December 6, 2020. EudraCT number: 2017-004444-38. Clinical trial information: NCT03673072 .

Hospital Regimens Including Probiotics Guide the Individual Development of the Gut Microbiome of Very Low Birth Weight Infants in the First Two Weeks of Life.

Background: It is unknown to what extent the microbiome of preterm infants is influenced by hospital regimens including the use of different probiotics when it comes to the prevention of necrotizing enterocolitis (NEC). Methods: Prospective controlled multicenter cohort study including very low birth weight infants from three neonatal intensive care units (NICUs) between October 2015 and March 2017. During this time span, stool was sampled every other day during the first two weeks and samples were subjected to amplicon-based microbiome analyses. Out of these, seventeen negative controls were processed (German Registry of Clinical Trials (No.: DRKS00009290)). Results: The groups (3 × 18 infants) showed no statistically significant difference regarding gestational age, birth weight, APGAR scores and oxygen demand. 2029 different taxa were detected, including Enterococcus and Staphylococcus, as well as the probiotic genera Lactobacillus and Bifidobacterium predominating. The bacterial load was found to increase earlier on when probiotics were used. Without probiotics administration, Lactobacillus and Bifidobacterium contributed only marginally to the fecal microbiome. Some infants did not respond to probiotic administration. The samples from all centers participating reached a very similar diversity after two weeks while the microbiome samples from all three centers clustered significantly yet varied from each other. Conclusion: Probiotics proved to be safe and initiated an earlier increase of bacterial load (with marked individual divergences), which might play a crucial role in the prevention of neonatal morbidities. Meconium was found not to be free of bacterial DNA, and oral antibiotics did not influence the fecal microbiome development negatively, and hospital regimes led to a center-specific, distinct cluster formation.

Incidence of Epidermal Necrolysis: Results of the German Registry

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are severe cutaneous adverse reactions resulting in wide-spread epidermal detachment and erosions of mucous membranes. They are considered as severity variants sharing the same pathogenesis and etiology and are, therefore, referred to as epidermal necrolysis (EN) (Mockenhaupt and Roujeau, 2019). Clinically, severity is distinguished on the basis of the amount of skin detachment: SJS < 10%, SJS/TEN overlap of 10–30%, and TEN > 30% (Bastuji-Garin et al., 1993a).

Effectiveness of a Home-Based Rehabilitation Program After Total Hip Arthroplasty Driven by a Tablet App and Remote Coaching: Nonrandomized Controlled Trial Combining a Single-Arm Intervention Cohort With Historical Controls.

BackgroundRecent technological developments such as wearable sensors and tablets with a mobile internet connection hold promise for providing electronic health home-based programs with remote coaching for patients following total hip arthroplasty. It can be hypothesized that such a home-based rehabilitation program can offer an effective alternative to usual care.ObjectiveThe aim of this study was to determine the effectiveness of a home-based rehabilitation program driven by a tablet app and remote coaching for patients following total hip arthroplasty.MethodsExisting data of two studies were combined, in which patients of a single-arm intervention study were matched with historical controls of an observational study. Patients aged 18-65 years who had undergone total hip arthroplasty as a treatment for primary or secondary osteoarthritis were included. The intervention consisted of a 12-week home-based rehabilitation program with video instructions on a tablet and remote coaching (intervention group). Patients were asked to do strengthening and walking exercises at least 5 days a week. Data of the intervention group were compared with those of patients who received usual care (control group). Effectiveness was measured at four moments (preoperatively, and 4 weeks, 12 weeks, and 6 months postoperatively) by means of functional tests (Timed Up & Go test and the Five Times Sit-to Stand Test) and self-reported questionnaires (Hip disability and Osteoarthritis Outcome Score [HOOS] and Short Form 36 [SF-36]). Each patient of the intervention group was matched with two patients of the control group. Patient characteristics were summarized with descriptive statistics. The 1:2 matching situation was analyzed with a conditional logistic regression. Effect sizes were calculated by Cohen d.ResultsOverall, 15 patients of the intervention group were included in this study, and 15 and 12 subjects from the control group were matched to the intervention group, respectively. The intervention group performed functional tests significantly faster at 12 weeks and 6 months postoperatively. The intervention group also scored significantly higher on the subscales “function in sport and recreational activities” and “hip-related quality of life” of HOOS, and on the subscale “physical role limitations” of SF-36 at 12 weeks and 6 months postoperatively. Large effect sizes were found on functional tests at 12 weeks and at 6 months (Cohen d=0.5-1.2), endorsed by effect sizes on the self-reported outcomes.ConclusionsOur results clearly demonstrate larger effects in the intervention group compared to the historical controls. These results imply that a home-based rehabilitation program delivered by means of internet technology after total hip arthroplasty can be more effective than usual care.Trial RegistrationClinicalTrials.gov NCT03846063; https://clinicaltrials.gov/ct2/show/NCT03846063 and German Registry of Clinical Trials DRKS00011345; https://tinyurl.com/yd32gmdo

Changes in treatment for NSTEMI in women and the elderly over the past 16 years in a large real-world population

AimsThis study investigates the changes in therapy for Non-ST-Elevation Myocardial Infarction (NSTEMI) over the past 16 years in a large German registry. In particular, the high-risk population of female and elderly patients was analyzed. MethodsIn total, 19.383 patients presenting with NSTEMI were included in this study. Patients were stratified by age groups <75 years and ≥75 years and by sex. Four different time periods from 2000–2004, 2005–2008, 2009–2012 and 2013–2016 were compared. Influence on hospital mortality as the primary outcome measure was assessed by logistic regression analysis. Secondary outcome measures included percutaneous coronary intervention (PCI), the use of drug eluting stents (DES), radial access route and major adverse cardiovascular events (MACE), defined as all-cause mortality, stroke, re-infarction, percutaneous re-intervention, intervention-related bleeding, cardiopulmonary resuscitation and new onset of cardiogenic shock or need for mechanical ventilation. ResultsMortality decreased in all age groups between the initial time period and the most recent one (8.9% vs. 4.5%, p < 0.01), particularly in female patients ≥75 years (18.2% in 2000–2004 vs. 7.9% in 2013–2016, p < 0.01). Revascularization rates differed by gender (68.3% in women vs. 78.1% in men, p < 0.01) and by age (64.2% for ≥75 years vs. 80.9% for <75 years, p < 0.01). PCI rates in elderly female patients increased from 28.7% to 69.8% (p < 0.01) from the initial to the latest period. ConclusionsThe present study demonstrates, that revascularization rates improved in all patient groups over the study period. However, females and elderly patients still remain less likely to be treated according to current guidelines.

Twelve-month outcome in juvenile proliferative lupus nephritis: results of the German registry study.

Children presenting with proliferative lupus nephritis (LN) are treated with intensified immunosuppressive protocols. Data on renal outcome and treatment toxicity is scare. Twelve-month renal outcome and comorbidity were assessed in 79 predominantly Caucasian children with proliferative LN reported to the Lupus Nephritis Registry of the German Society of Paediatric Nephrology diagnosed between 1997 and 2015. At the time of diagnosis, median age was 13.7 (interquartile range 11.8-15.8) years; 86% showed WHO histology class IV, nephrotic range proteinuria was noted in 55%, and median estimated glomerular filtration rate amounted to 75ml/min/1.73m2. At 12months, the percentage of patients with complete and partial remission was 38% and 41%, respectively. Six percent of patients were non-responders and 15% presented with renal flare. Nephrotic range proteinuria at the time of diagnosis was associated with inferior renal outcome (odds ratio 5.34, 95% confidence interval 1.26-22.62, p = 0.02), whereas all other variables including mode of immune-suppressive treatment (e.g., induction treatment with cyclophosphamide (IVCYC) versus mycophenolate mofetil (MMF)) were not significant correlates. Complications were reported in 80% of patients including glucocorticoid toxicity in 42% (Cushingoid appearance, striae distensae, cataract, or osteonecrosis), leukopenia in 37%, infection in 23%, and menstrual disorder in 20%. Growth impairment, more pronounced in boys than girls, was noted in 78% of patients. In this cohort of juvenile proliferative LN, renal outcome at 12months was good irrespectively if patients received induction treatment with MMF or IVCYC, but glucocorticoid toxicity was very high underscoring the need for corticoid sparing protocols. Graphical abstract.

Hemophagocytic lymphohistiocytosis in adults: collaborative analysis of 137 cases of a nationwide German registry

PurposeHemophagocytic lymphohistiocytosis (HLH) is a severe hyperinflammatory syndrome emerging from a deregulated immune response due to various triggers. In adults, systematic data are sparse, which is why recommendations on diagnosis and management have been adopted from pediatric guidelines. A nationwide clinical registry with associated consulting service as collaborative initiative of HLH-specialized pediatricians and hematologists was initiated to better characterize HLH in adults.MethodsPatients with proven or suspected HLH were registered by 44 institutions. Both HLH-2004 diagnostic criteria and the HScore (www.saintantoine.aphp.fr/score/) were used to confirm HLH diagnosis. Data referring to underlying disease, treatment, outcome, clinical presentation and laboratory findings were recorded.ResultsThe study included 137 patients and provides the first systematic data on adult HLH in Germany. Median age was 50 years with a wide range (17–87 years), 87 patients (63.5%) were male. Most common triggering diseases were infections in 61 patients (44.5%) and malignancies in 48 patients (35%). Virtually all patients had elevated ferritin concentrations, and 74% had peak concentrations greater than 10,000 µg/l. At time of analysis, 67 of 131 patients (51%) had died. Patients with malignancy-associated HLH had the shortest median survival (160 days), however no statistically significant difference between subgroups was observed (p = 0.077). Platelets under 20*109/l and low albumin concentrations (< 20 g/l) were associated with poor overall and 30-day survival.ConclusionClose multidisciplinary case consultation and cooperation is mandatory when treating adult HLH patients. Early contact with reference centers is recommended, especially in relapsing or refractory disease.

Neoadjuvant chemotherapy with gemcitabine plus cisplatin followed by radical liver resection versus immediate radical liver resection alone with or without adjuvant chemotherapy in incidentally detected gallbladder carcinoma after simple cholecystectomy or in front of radical resection of BTC (ICC/ECC) \u2013 a phase III study of the German registry of incidental gallbladder carcinoma platform (GR)\u2013 the AIO/ CALGP/ ACO- GAIN-trial \u2013

BackgroundCurrently, complete surgical resection represents the only potentially curative treatment option for Biliary Tract Cancer (BTC) including Gallbladder Cancer (GBC). Even after curative resection, 5-year OS is only 20–40%. Gallbladder carcinoma is relatively rare, but still the fifth most common neoplasm of the digestive tract and even the most frequent cancer of the biliary system. Gallbladder carcinoma is suspected preoperatively in only 30% of all pts., while the majority of cases are discovered incidentally by the pathologist after cholecystectomy for a benign indication. For improving curative rates in BTC and GBC, early systemic therapy combined with radical resection seems to be a promising approach. The earliest moment to apply chemotherapy would be in front of radical surgery. The encouraging results of neoadjuvant/perioperative concepts in other malignancies provide an additional rationale to use this treatment in the early phase of GBC management and even ICC/ECC. Especially because data regarding pure adjuvant chemotherapy in BTC’s are conflicting.MethodsThis is a multicenter, randomized, controlled, open-label phase III study including pts. with incidentally discovered GBCs after simple cholecystectomy in front of radical liver resection and pts. with resectable/ borderline resectable cholangiocarcinomas (ICC/ ECC) scheduled to receive perioperative chemotherapy (Gemcitabine + Cisplatin 3 cycles pre- and post-surgery) or surgery alone followed by a therapy of investigator’s choice. Primary endpoint is OS; secondary endpoints are PFS, R0-resection rate, toxicity, perioperative morbidity, mortality and QoL. A total of N = 333 patients with GBC or BTC will be included. Recruitment has started in August 2019.DiscussionThe current proposed phase III GAIN study investigates whether induction chemotherapy followed by radical resection in ICC/ECC and re-resection in IGBC (and – if possible – postoperative chemotherapy) prolongs overall survival compared to radical surgery alone for incidental gallbladder carcinoma and primary resectable or borderline resectable cholangiocarcinoma. Utilizing a neoadjuvant approach including a second radical surgery will help to raise awareness for the necessity of radical surgery, especially second radical completion surgery in IGBC and improve the adherence to the guidelines.Trial registrationClinicalTrials.gov ID: NCT03673072 from 17.09.2018. EudraCT number: 2017–004444-38 from 02.11.2017.