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Simple Summary: This multicenter study (n = 1133, inclusion criteria: 3.5 cm maximum tumor size and preoperative indication for a boost) provides detailed data on acute and long-term toxicities in breast cancer patients undergoing breast-conserving surgery combined with an anticipated intraoperative boost with low-energy X-rays followed by whole breast irradiation. Toxicity assessments, based on LENT SOMA criteria, were performed annually up to 10 years of follow-up. IORT boost was completed in 90% and EBRT in 97% of cases. No grade 3 or 4 acute toxicities were observed, with mild acute side effects reported in a small proportion of patients. Chronic toxicities were seen in 16.2% of patients with teleangiectasia, 14.3% with grade ≥ 2 fibrosis, 3.4% with grade ≥ 2 pain, and 1.1% with hyperpigmentation. The results show that the therapy is safe and feasible in terms of toxicity and confirms intraoperative boost as a standard method of boost application in a large prospective cohort. In the context of breast cancer treatment optimization, this study prospectively examines the feasibility and outcomes of utilizing intraoperative radiotherapy (IORT) as a boost in combination with standard external beam radiotherapy (EBRT) for high-risk patients. Different guidelines recommend such a tumor bed boost in addition to whole breast irradiation with EBRT for patients with risk factors for local breast cancer recurrence. The TARGIT BQR (NCT01440010) is a prospective, multicenter registry study aimed at ensuring the quality of clinical outcomes. It provides, for the first time, data from a large cohort with a detailed assessment of acute and long-term toxicity following an IORT boost using low-energy X-rays. Inclusion criteria encompassed tumors up to 3.5 cm in size and preoperative indications for a boost. The IORT boost, administered immediately after tumor resection, delivered a single dose of 20 Gy. EBRT and systemic therapy adhered to local tumor board recommendations. Follow-up for toxicity assessment (LENT SOMA criteria: fibrosis, teleangiectasia, retraction, pain, breast edema, lymphedema, hyperpigmentation, ulceration) took place before surgery, 6 weeks to 90 days after EBRT, 6 months after IORT, and then annually using standardized case report forms (CRFs). Between 2011 and 2020, 1133 patients from 10 centers were preoperatively enrolled. The planned IORT boost was conducted in 90%, and EBRT in 97% of cases. Median follow-up was 32 months (range 1–120, 20.4% dropped out), with a median age of 61 years (range 30–90). No acute grade 3 or 4 toxicities were observed. Acute side effects included erythema grade 1 or 2 in 4.4%, palpable seroma in 9.1%, punctured seroma in 0.3%, and wound healing disorders in 2.1%. Overall, chronic teleangiectasia of any grade occurred in 16.2%, fibrosis grade ≥ 2 in 14.3%, pain grade ≥ 2 in 3.4%, and hyperpigmentation in 1.1%. In conclusion, a tumor bed boost through IORT using low-energy X-rays is a swift and feasible method that demonstrates low rates in terms of acute or long-term toxicity profiles in combination with whole breast irradiation. [ABSTRACT FROM AUTHOR]

Purpose: The primary aim was to compare the prevalence of acute and delayed intracranial haemorrhage (ICH) following mild traumatic brain injury (mTBI) in patients on antithrombotic medication referred to a clinic for oral and plastic maxillofacial surgery. The secondary aim was to evaluate the need for short-term hospitalisation based on initial radiological and clinical findings. Methods: This was an observational retrospective single-centre study of all patients on antithrombotic medication who were admitted to our department of oral and plastic maxillofacial surgery with mTBI over a 5 year period. Demographic and anamnesis data, injury characteristics, antithrombotic medication, radiological findings, treatment, and outcome were analysed. Patients were divided into the following four groups based on their antithrombotic medication: (1) single antiplatelet users, (2) vitamin K antagonist users, (3) direct oral anticoagulant users, and (4) double antithrombotic users. All patients underwent an emergency cranial CT (CT0) at admission. Based on clinical and radiological evaluation, different treatment protocols were applied. Patients with positive CT0 findings and patients with secondary neurological deterioration received a control CT (CT1) before discharge. Acute and delayed ICH and patient's outcome during hospitalisation were evaluated using descriptive statistical analysis. Results: A total of 696 patients (mean age, 71.6 years) on antithrombotic medication who presented at our department with mTBI were included in the analysis. Most injuries were caused by a ground-level fall (76.9%). Thirty-six patients (5.1%) developed an acute traumatic ICH, and 47 intracerebral lesions were detected by radiology—most of these in patients taking acetylsalicylic acid. No association was detected between ICH and antithrombotic medication (p = 0.4353). In total, 258 (37.1%) patients were admitted for 48 h in-hospital observation. The prevalence of delayed ICH was 0.1%, and the mortality rate was 0.1%. Multivariable analysis identified a Glasgow Coma Scale (GCS) of < 15, loss of consciousness, amnesia, headache, dizziness, and nausea as clinical characteristics significantly associated with an increased risk of acute ICH, whereas age, sex, and trauma mechanism were not associated with ICH prevalence. Of the 39 patients who underwent a control CT1, most had a decreasing or at least constant intracranial lesion; in three patients, intracranial bleeding increased but was not clinically relevant. Conclusion: According to our experience, antithrombotic therapy does not increase the rate of ICH after mTBI. A GCS of < 15, loss of consciousness, amnesia, headache, dizziness, and nausea are indicators of higher ICH risk. A second CT scan is more effective in patients with secondary neurological deterioration. Initial CT findings were not clinically relevant and should not indicate in-hospital observation. [ABSTRACT FROM AUTHOR]

Background/Aim: The aim of this study was to evaluate patient preferences regarding cervical dysplasia clinics. Specifically, preferences in terms of diagnostic and therapeutic pathways as well as logistical and structural aspects were addressed to recognize unmet needs and improve existing structures of cervical dysplasia care. Patients and Methods: This questionnaire-based study was conducted between June and December 2022 at an academic medical center in Southwestern Germany. A total of 226 patients who had an appointment at the certified dysplasia clinic were included. Results: The vast majority of patients (74.8%) preferred counseling at the certified dysplasia clinic in the case of an abnormal finding of the cervix or labia. A prompt appointment (within a maximum of 4 weeks), a timely notification about test results (within a maximum of 2 weeks), a travel time <60 minutes and seeing the same doctor during follow-up appointments were recognized as important aspects. While about half of the patients (53.5%) were indifferent to the sex of the gynecologist, almost all of the remaining patients stated they would prefer to be seen by a female doctor (44.3% female doctor vs. 2.2% male doctor). Conclusion: Most women expect very timely appointments and result notifications. Moreover, they favor short travel times and continuity of care. The identified patient preferences should be considered to increase patient satisfaction and quality of care when developing and optimizing management at specialized dysplasia clinics. [ABSTRACT FROM AUTHOR]

Purpose: According to the recently implemented organized cervical cancer screening program in Germany, women older than 35 years with negative cytology but persistent high-risk human papilloma virus (hrHPV) infection > 12 months should be referred to colposcopy for further evaluation. This study aimed to present and dissect colposcopic and histopathological findings with particular focus on associated hrHPV genotypes. Methods: This study is a retrospective analysis of clinical data from 89 hrHPV positive patients with normal cytology who underwent colposcopic examination at a certified dysplasia outpatient clinic in Germany in 2021. Results: While 38 (43%) women had a normal colposcopic finding, 45 (51%) had minor and 6 (7%) major changes. Thirty-one (35%) of the women were HPV 16 and/or HPV 18 positive and 58 (65%) women were positive for other hrHPV only. Among patients who underwent colposcopy with biopsies (in case of an abnormal finding or type 3 transformation zone, n = 68), eight (12%) had cervical intraepithelial neoplasia (CIN) 3 and six (9%) had CIN 2. The proportion of women diagnosed with CIN 3 varied among different hrHPV genotypes (HPV 16: 11%, HPV 18: 33%, HPV 31: 27%, HPV 33: 33%, HPV 52: 33%). Conclusion: Persistently hrHPV positive women with negative cytology are at increased risk of being diagnosed with CIN 3. As CIN 3 prevalence seems to differ with regard to hrHPV strain, immediate HPV genotyping for risk stratification and subsequent early referral for colposcopy might constitute a feasible strategy. [ABSTRACT FROM AUTHOR]

The aim of this study was to correlate ventricular size and volumes of deep gray matter (DGM) in MRI at term equivalent age (TEA) with outcome at a corrected age of 24 months in preterm infants and with handedness. Seventy-three infants born before 32 weeks of gestation or with birth weight < 1500 g  were included in this retrospective analysis and measurement of lateral ventricles, and DGM was performed on MRI scans. The left lateral ventricle was significantly larger than the right lateral ventricle (p = 0.001). There was no correlation between volumes of the right and left ventricles and the DGM volume (p = 0.207 and p = 0.597, respectively), nor with the head circumference at TEA (p = 0.177 and p = 0.976, respectively). The total volume of both lateral ventricles did not correlate with Mental Develomental Index (MDI, p = 0.336) or Psychomotor Developmental Index (PDI, p = 0.650) score (Bayley Scales of Infant Development, BSID II). However, a correlation of total DGM volume with birth weight (p = 0.0001; r = 0.437), head circumference at TEA (p < 0.0001; r = 0.640), MDI (p = 0.029; r = 0.310), and PDI (p = 0.002; r = 0.456) was observed. No significant difference between right- and left-handed infants was seen in relation to volumes of both lateral ventricles and of DGM.Conclusion: DGM volume at TEA was significantly associated with the outcome at a corrected age of 24 months. Handedness did not correlate with DGM or lateral ventricle size.What is Known:• White matter injury as well as altered development of deep gray matter is associated with neurodevelopmental disability in preterm infants.• No study analyzed the association between deep gray matter volume or volumes of lateral ventricle and handedness in former preterm infants so far.What is New:• Volume of deep gray matter, but not lateral ventricular size was significantly associated with outcome at a corrected age of 24 months in preterm infants.• There was no correlation of handedness with volumes of lateral ventricular size or with deep gray matter volumes. [ABSTRACT FROM AUTHOR]

Background/Aims: The prevalence and incidence of autoimmune pancreatitis (AiP) in those living in western countries are largely unknown. We aimed to determine the prevalence of AiP among patients with pancreatitis presenting to our tertiary referral center in Mannheim, Germany; and to estimate the incidence of AiP in the Southwest of Germany. Methods: We performed a retrospective cross-sectional analysis and determined the prevalence of AiP in patients with acute pancreatitis (AP) or chronic pancreatitis (CP). Patients (n = 704; alcoholic pancreatitis n = 373, nonalcoholic pancreatitis n = 331) were stratified into the Retrospective-Pancreas-Cohort (RPC, period 1998-2008, n = 534) and the Pancreas-Clinic-Cohort (PCC, periods 2008-2010 and 2013-2014, n = 170, with detailed investigation for features of AiP). Diagnosis of AiP was established by International-Consensus-Diagnostic-Criteria and Unifying-Autoimmune-Pancreatitis-Criteria. Results: In the RPC, the prevalence of AiP was 5.9% (n = 13/221) among individuals with nonalcoholic pancreatitis (n = 1/61 with AP, 1.6%; n = 12/160 with CP, 7.5%). In the PCC, the prevalence of AiP was 9.1% (n = 10/110) among patients with nonalcoholic pancreatitis (n = 2/24 with AP, 8.3%; n = 8/86 with CP, 9.3%), and 1.7% (n = 1/60) among subjects with alcoholic pancreatitis. We estimated the incidence of AiP with 0.29 per 100,000 population each year. Conclusion: The prevalence rate of AiP may account for 9% of patients with nonalcoholic pancreatitis but is almost never observed in patients with alcoholic pancreatitis. The incidence of AiP in Germany appears lower than 1 per 100,000 population. [ABSTRACT FROM AUTHOR]

Purpose: Conventional radiography is frequently performed in pediatric patients in whom fractures and dislocations are suspected. However, until now, the rate of positive findings of the most commonly performed radiographic examinations in pediatric patients is unknown. The aim of this study was to evaluate the number of positive findings in the 20 most frequently requested standard radiographic examinations in pediatric patients in a level 1 trauma center systematically.Methods: A transversal cohort study was conducted at a level 1 trauma center in Germany (2008-2014). In a statistical pre hoc analysis, a sample size of 200 images of each standard radiograph was determined. The picture archiving and communication system (PACS) was searched for radiographic examinations in patients under 18 years.Results: The following fracture rates for the investigated 20 most common examinations were found: 70.5% clavicle, 54.5% forearm, 53% wrist, 41.5% elbow, 30.5% lower leg, 20% hand, 18.5% finger, 12.5% toe, 12% forefoot, 11.5% ankle, 9% shoulder, 6.5% patella, 5.5% foot, 4% knee, 2% conventional rib series, 1.5% lumbar spine, 1% Towne view, 0.5% skull, 0% cervical spine, and 0% odontoid. Differences in the mean age of analyzed pediatric trauma patients in correlation to different standard radiographs were found.Conclusions: In our study, a relevant amount of different standard radiographs revealed a low fracture rate. Therefore, indications for X-ray should be checked properly and alternative procedures should be discussed with the patient and the parents. Clinical decision rules should be developed and pathways have to be implemented to minimize radiation exposure, waiting time, and costs. [ABSTRACT FROM AUTHOR]

Background/Aims: Autoimmune pancreatitis (AIP) has been associated with an increased risk of malignant diseases. We aimed to describe the incidence of malignant diseases in patients with AIP compared to the general population and to characterize the clinical presentation of these patients. Methods: We retrospectively analyzed data from 28 patients with AIP presenting to the clinic (periods 1998 until 2010, 2012 until September 2015). We retrieved the expected cancer incidence of the general population from the German cancer registry. We determined the ratio of patients with malignant disease, characterized the clinical presentation of these patients, and calculated standardized incidence ratios (SIR). Results: We observed 6 malignant diseases in 5 patients with AIP (non-Hodgkin lymphoma, colon cancer, breast cancer and ovarian carcinoma, breast cancer, bladder cancer, n = 5/28, 17.9%) during an overall observation period of 223 person-years (2,675 months). The overall SIR of cancer in patients with AIP was 17.3 (95% CI 5.9-35.8), and the over-all incidence rate of malignant diseases in these patients was significantly increased compared to the expected incidence in the German population (Fisher's exact test, p < 0.001). Conclusion: The incidence of malignant diseases in patients with AIP is significantly increased compared to the general population. Careful clinical monitoring is required in individuals with AIP to exclude the occurrence of malignancy. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented related to Fit fOR The Aged (FORTA), a clinical tool for improved pharmacotherapy in the elderly.

Introduction: Adherence to follow-up (FU) care after bariatric surgery is poor despite strong recommendations. In our pilot Bella trial, we demonstrated that a completely remote follow-up program via smartphone is feasible and safe for patients after bariatric surgery. Building on this, we aim to verify our results in a multicenter, randomized controlled setting., Methods: This trial plans to enroll 410 participants undergoing primary bariatric surgery in seven German bariatric centers. Participants are randomized into two groups: a control group receiving in-person FU according to the standard in the bariatric centers, and an interventional group monitored using a smartphone application (app). The app sends standardized questionnaires and reminders regarding regular vitamin intake and exercises. The built-in messaging function enables patients to communicate remotely with medical care professionals. After one year, all participants are evaluated at their primary bariatric centers. The primary outcome is weight loss 12 months after surgery. The secondary outcomes include obesity-related comorbidities, quality of life, serum values of vitamins and minerals, body impedance analysis, visits to the emergency department or readmission, patient compliance, and medical staff workload., Discussion: The current study is the first prospective, individually randomized-controlled, multicenter trial where a mobile application completely replaces traditional in-person visits for post-bariatric surgery follow-ups in bariatric centers., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

The positive side of the Covid-19 pandemic is that it has provided a stimulation for innovations. As an example, we discuss the Pragmatic Controlled Trial (PCT), a twin study that can be used to confirm the real-world effectiveness (RWE) of health services under the non-standardized conditions of everyday care. Proof of the RWE could generally be important for health services with conditional approval. The PCT uses the Bayesian principle instead of randomization. It enables care under non-standardized everyday conditions and, by describing the endpoint-specific risks of each individual patient and by classifying the interventions, creates an unbiased evaluation in a non-experimental, but risk-stratified and controlled study. Patients expect a timely solution to their health problems. Until now, science has required sufficiently well-founded results before approving an innovation. The Covid-19 pandemic has shown that the demand for immediate and best possible care can be met through the conditional approval of a new care principle. With the PCT, we describe a procedure with which, after conditional approval, the missing data can be collected in order to successfully complete the approval process., Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht., (Thieme. All rights reserved.)

Objectives: To assess the frequency of antenatal corticosteroid (ACS) administration in cases with shortened cervical length by addition of placental alpha-microglobulin-1 (PAMG-1) testing to sonographic examination., Methods: Single centre retrospective cohort study. Rate of ACS administration was compared between cases with cervical length between 15 and 25 mm and cases with positive PAMG-1 testing and cervical length between 15 and 25 mm. We evaluated the following outcome parameters: Rate of ACS administration, gestational age at delivery, time to delivery, delivery within seven days, delivery <34 and <37 weeks' gestation, rate of admission to neonatal intensive care unit (NICU)., Results: In total, 130 cases were included. "PAMG-1 group" consisted of 68 women, 62 cases built the "historical control group". ACS administration was performed less frequently in the "PAMG-1 cohort" (18 (26%) vs. 46 (74%); p<0.001). The rate of delivery within seven days did not differ (2 (3%) vs. 4 (6.5%); p=0.4239). The rates of delivery <34 weeks' gestation (7 (10%) vs. 9 (15%); p=0.4643) and <37 weeks' gestation (19 (28%) vs. 26 (42%); p=0.0939) did not differ. Time to delivery interval was longer in the PAMG-1 group (61.5 vs. 43 days, p=0.0117). NICU admission occurred more often in the "historical control group" (22 (38%) vs. 28 (60%); p=0.0272)., Conclusions: Addition of biomarker testing can help to avoid unnecessary ACS administrations in women with shortened cervical length., (© 2021 Walter de Gruyter GmbH, Berlin/Boston.)

Background: The unexpected outbreak of the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused more than 49 million cases and an estimated 2,000,000 associated deaths worldwide. In Germany, there are currently more than 2,000,000 laboratory-confirmed coronavirus disease 2019 (COVID-19) cases including 51,800 deaths. However, regional differences also became apparent and with the second wave of infections, the detailed characterization of COVID-19 patients is crucial to early diagnosis and disruption of chains of infections., Methods: Handing out detailed questionnaires to all individuals tested for COVID-19, we evaluated the clinical characteristics of negative and positive tested individuals. Expression of symptoms, symptom duration and association between predictor variables (i.e. age, gender) and a binary outcome (olfactory and gustatory dysfunction) were assessed., Results: Overall, the most common symptoms among individuals who tested positive for SARS-CoV-2 were fatigue, headache, and cough. Olfactory and gustatory dysfunction were also reported by many SARS-CoV-2 negative individuals, more than 20% of SARS-CoV-2 negative tested individuals in our study reported olfactory and gustatory dysfunction. Independent of SARS-CoV-2 status, more females displayed symptoms of gustatory (29.8%, p = 0.0041) and olfactory dysfunction (22.9%, p = 0.0174) compared to men., Conclusions: Bringing early SARS-CoV-2 tests to the populations at risk must be a main focus for the upcoming months. The reliability of olfactory and gustatory dysfunction in COVID-19 negative tested individuals requires deeper investigation in the future.

Introduction: Scientific evidence in medicine is based on data generated from research. Recently, the number of scientifically active physicians has decreased, which has led to the development of the Clinician Scientist Programs. To better structure and focus the research of young physicians, we aimed to investigate the impact of collaborations and other factors on the quality and output of scientific publications., Methods: The abstracts of three annual congresses of the German Society of Urology were systematically analysed regarding content, collaborations, and study design. Full-text publications and journals were identified through a MEDLINE® search. Impact factors (IFs) were identified using Journal Citation Reports™. To identify factors which predict publication and IFs, χ 2 and Wilcoxon rank-sum tests were used. Uni- and multivariable logistic regression analyses were performed to assess the best model for publication success for an abstract as well as the achievement of a high IF., Results: 1,074 abstracts were reviewed. The publication rate of subsequent peer-reviewed full-text publications was 52.5%. Collaborations with at least one institution (odds ratio (OR) 2.02, 95% confidence interval (CI) 1.48-2.76, p <0.0001), statistical analysis (OR 1.92, 95% CI 1.41-2.60, p <0.0001), study design (prospective vs. retrospective: OR 1.43, 95% CI 1.06-1.93, p=0.021), and national collaborations (OR 1.43, 95% CI 1.04-1.98, p=0.029) increased the likelihood of publication in a peer-reviewed journal in a multivariable logistic regression analysis. Experimental design (OR 2.77, 95% CI 1.32-5.84, p=0.007), international collaborations (OR 2.26, 95% CI 1.23-4.15, p=0.009), oncologic topics (OR 1.94, 95% CI 1.23-3.07, p=0.005), prostate disease (OR 1.75, 95% CI 1.08-2.84, p=0.023), and statistical analysis (OR 1.68, 95% CI 1.06-2.64, p=0.026) were associated with a higher IF., Conclusion: Abstracts resulting from collaborative research projects had a higher likelihood of subsequent full-text publication and a higher IF. More full-text publications were reported when abstracts included a statistical analysis. Hence, intensive networking (e. g. at congresses and workshops) of researching physicians as well as statistical/biometrical classes could be key factors to improve academic success., (Copyright © 2021. Published by Elsevier GmbH.)

Background: In contrast to adults, for whom guidelines on the cholelithiasis treatment exist, there is no consistent treatment of pediatric patients with cholelithiasis throughout national and international departments, most probably due to the lack of evidence-based studies., Methods: We evaluated the German management of pediatric cholelithiasis in a dual approach. Firstly, a retrospective, inter-divisional study was established, comparing diagnostics and therapy of patients of the pediatric surgery department with the management of patients aged < 25 years of the visceral surgery department in our institution over the past ten years. Secondarily, a nation-wide online survey was implemented through the German Society of Pediatric Surgery., Results: Management of pediatric patients with cholelithiasis was primarily performed by pediatricians in the retrospective analysis (p < 0.001). Pediatric complicated cholelithiasis was not managed acutely in the majority of cases with a median time between diagnosis and surgery of 22 days (range 4 days-8 months vs. 3 days in visceral surgery subgroup (range 0 days-10 months), p = 0.003). However, the outcome remained comparable. The hospital's own results triggered a nation-wide survey with a response rate of 38%. Primary pediatric medical management of patients was confirmed by 36 respondents (71%). In case of acute cholecystitis, 22% of participants perform a cholecystectomy within 24 h after diagnosis. Open questions revealed that complicated cholelithiasis is managed individually., Conclusions: The management of pediatric cholelithiasis differs between various hospitals and between pediatricians and pediatric surgeons. Evidence-based large-scale population studies as well as a common guideline may represent very important tools for treating this increasing diagnosis.

Background: Little is known about the epidemiology of advanced systemic mastocytosis (advSM)., Objectives: To investigate epidemiologic features and diagnostic pitfalls of advSM in Germany., Methods: Therefore, 140 patients from a single German reference center of the European Competence Network on Mastocytosis between 2003 and 2018 were analyzed., Results: The patients' median age was 68 years (range, 26-86 years), and male versus female ratio was 2:1. An elevated serum tryptase, a KIT D816 mutation, and additional somatic mutations, for example, in SRSF2, ASXL1, or RUNX1, were identified in 95%, 91%, and 74% of patients, respectively. Median overall survival was 3.5 years (range, 0.03-14.3 years; male vs female 2.6 vs 4.2 years; P = .02). Two categories of misdiagnoses were identified in 51 of 140 (36%) patients: First, systemic mastocytosis (SM) was overlooked in 28 of 140 (20%) patients primarily diagnosed with various subtypes of myeloid neoplasms. Second, 23 of 140 (16%) patients were diagnosed with supposed progression from indolent SM to advSM; however, combination of an elevated KIT D816V variant allele frequency in peripheral blood (n = 22), monocytosis (n = 9), eosinophilia (n = 6), and/or mutations in SRSF2, ASXL1, or RUNX1 (n = 10) suggest that distinct signs of potential advSM were overlooked in virtually all patients. Based on locally diagnosed patients in an area of 2.5 million inhabitants, but obviously without considering more, yet unrecognized cases, the incidence and prevalence of advSM is at least 0.8 and 5.2, respectively, per 1 million inhabitants., Conclusions: Adequate analyses of tryptase levels, bone marrow morphology, and genetics in patients with myeloid neoplasms or SM would help to prevent the significant underdiagnosis of advSM., (Copyright © 2020 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

The study sought to assess the impact of chronic kidney disease (CKD) on recurrences of ventricular tachyarrhythmias in implantable cardioverter defibrillator (ICD) recipients. Data regarding the outcome of patients with CKD in ICD recipients is limited. A large retrospective registry was used including consecutive ICD recipients surviving episodes of ventricular tachycardia (VT) or fibrillation (VF) from 2002 to 2016. CKD patients were compared to non-CKD patients. The primary endpoint was the first recurrence of ventricular tachyarrhythmias at 5 years. Secondary endpoints were ICD-related therapies, rehospitalization and all-cause mortality at 5 years. Kaplan-Meier, multivariable Cox regression and propensity score matching were applied. A total of 585 consecutive patients were included (non-CKD: 57%, CKD: 43%). CKD had higher rates of the primary endpoint of recurrent ventricular tachyarrhythmias compared to non-CKD patients (50% vs. 40%; log rank p = 0.008; HR = 1.398; 95% CI 1.087-1.770; p = 0.009), which was irrespective of a primary or secondary preventive ICD and mainly attributed to recurrent VF (11% vs. 5%; p = 0.007) and electrical storm (ES) (10% vs. 5%; p = 0.010). Accordingly, CKD patients had higher rates of the secondary endpoint of appropriate ICD therapies (41% vs. 30%; log rank p = 0.002; HR = 1.532; 95% CI 1.163-2.018; p = 0.002), mainly attributed to appropriate ICD shocks (19% vs. 11%; p = 0.005). After multivariable Cox regression CKD was associated with a 1.4-fold higher risk of appropriate device therapies (HR = 1.353; 95% CI 1.001-1.825; p = 0.049), but not with first recurrence of ventricular tachyarrhythmias (p = 0.177). Irrespective of propensity score matching, CKD was associated with increasing all-cause mortality at 5 years (p = 0.001). The presence of CKD is associated with increased rates of recurrent ventricular tachyarrhythmias, appropriate device therapies, mainly attributed to appropriate shock, and all-cause mortality in ICD recipients at 5 years.

Background: Globalization and climate change increase the likelihood of a global spread of high consequence infectious diseases., Objectives: We analyzed how outpatient physicians in Germany were prepared to recognize and handle potential Ebola virus-infected patients during the recent Ebola outbreak in West Africa., Materials and Methods: Outpatient physicians participated in 2 anonymous surveys (n=166 and 129, respectively) and were asked, among others, about their knowledge of Ebola virus disease, their subjective perception of their own knowledge and the practical implementation in their daily routine. This was compared to a minimum standard defined by 14 members of the German "Permanent Working Group of Competence and Treatment Centres for high consequence infectious diseases" (STAKOB)., Results: The Ebola virus-specific knowledge of participants was significantly inferior compared to the defined minimum standard. Of 8 factual questions, an average of merely 5 was answered correctly. The physicians' subjective perception of knowledge presented as 'little'. Although 56% of participants indicated that they had received standard operation procedures, 64% had not implemented them into their daily routine. Merely 22% of surveyed medical doctors participated in Ebola virus-specific education programs. Yet participation led to a significantly better subjective knowledge perception., Conclusions: Contrary to the official assessment that Germany is well prepared for high consequence infectious diseases, this study suggests that there are deficits in this area. Despite the abundance of information about Ebola virus disease, preparation of outpatient physicians in Germany was inadequate. Yet nearly half of the participants indicated the potential risk of occurrence as 'likely' or 'very likely'. The presented data show the different consequences to be drawn regarding potential future crises and further research., Competing Interests: Die Autoren geben an, dass kein Interessenkonflikt besteht., (© Georg Thieme Verlag KG Stuttgart · New York.)

Purpose: The study sought to evaluate the prognostic impact of recurrences of ventricular tachyarrhythmias in consecutive ICD recipients with ventricular tachyarrhythmias on admission., Methods: All consecutive patients surviving at least one episode of ventricular tachyarrhythmias from 2002 to 2016 and discharged with an ICD (pre-existing ICD or ICD implantation at index hospitalization) were included. The primary endpoint was all-cause mortality according to the presence or absence of recurrences of ventricular tachyarrhythmias at 5 years. Secondary endpoints comprised the impact of different types of recurrences, appropriate ICD therapies, as well as predictors of recurrences and appropriate ICD therapies. Kaplan-Meier, multivariable Cox regression and propensity score matching analyses were applied., Results: A total of 592 consecutive ICD recipients was included (44% with recurrences of ventricular tachyarrhythmias and 56% without). Recurrences of ventricular tachyarrhythmias were associated with increased all-cause mortality at 5 years (HR = 1.498; 95% CI = 1.052-2.132; p = 0.025). Worst survival was observed in patients with sustained VT or VF as first recurrences compared to non-sustained VT, as well as in patients with cumulative recurrences of non-sustained or sustained VT plus VF, whereas mortality was not affected by the number of recurrences of ventricular tachyarrhythmias (> 4 vs. ≤ 4). Moreover, appropriate ICD therapies were associated with increased all-cause mortality (HR = 1.874; 95% CI = 1.318-2.666; p = 0.001), mainly attributed to secondary preventive ICDs. Finally, atrial fibrillation, LVEF < 35% and non-ischemic cardiomyopathy were identified as predictors of recurrences of ventricular tachyarrhythmias and appropriate ICD therapies., Conclusions: Recurrences of ventricular tachyarrhythmias and recurrent appropriate ICD therapies are associated with increased long-term all-cause mortality in consecutive ICD recipients. Non-ischemic cardiomyopathy, AF and LVEF < 35% revealed to be significant predictors of both endpoints.

Background: Demographic change concurrent with medical progress leads to an increasing number of elderly patients in intensive care units (ICUs). Antibacterial treatment is an important, often life-saving, aspect of intensive care but burdened by the associated antimicrobial resistance risk. Elderly patients are simultaneously at greater risk of infections and may be more restrictively treated because, generally, treatment intensity declines with age. We therefore described utilization of antibacterials in ICU patients older and younger than 80 years and examined differences in the intensity of antibacterial therapy between both groups., Methods: We analysed 17,464 valid admissions from the electronic patient data management system of our surgical ICU from April 2006 - October 2013. Antibacterial treatment rates were defined as days of treatment (exposed patient days) relative to patient days of ICU stay and calculated for old and young patients. Rates were compared in zero-inflated Poisson regression models adjusted for patients' sex, mean SAPS II- and TISS-scores, and calendar years yielding adjusted rate ratios (aRRs). Rate ratios exceeding 1 represent higher rates in old patients reflecting greater treatment intensity in old compared to younger patients., Results: Observed antibacterial treatment rates were lower in patients 80 years and older compared to younger patients (30.97 and 39.73 exposed patient days per 100 patient days in the ICU, respectively). No difference in treatment intensity, however, was found from zero-inflated Poisson regression models permitting more adequate consideration of patient days with low treatment probability: for all antibacterials the adjusted rate ratio (aRR) was 1.02 (95%CI: 0.98-1.07). Treatment intensities were higher in elderly patients for penicillins (aRR 1.37 (95%CI: 1.26-1.48)), cephalosporins (aRR 1.20 (95%CI: 1.09-1.31)), carbapenems (aRR 1.35 (95%CI: 1.20-1.50)), fluoroquinolones (aRR 1.17 (95%CI: 1.05-1.30), and imidazoles (aRR 1.34 (95%CI: 1.23-1.46))., Conclusions: Elderly patients were generally less likely to be treated with antibacterials. This observation, however, did not persist in patients with comparable treatment probability. In these, antibacterial treatment intensity did not differ between younger and older ICU patients, for some antibacterial classes treatment intensity was even higher in the latter. Patient-level covariates are instrumental for a nuanced evaluation of age-effects in antibacterial treatment in the ICU.

Background: Ventricular tachyarrhythmias are still associated with poor clinical outcomes. Therefore, it is important to stratify high-risk patients presenting with ventricular tachyarrhythmias for their individual risk of future outcomes., Aim: To assess the impact of male sex on survival in patients presenting with ventricular tachyarrhythmias., Methods: All consecutive patients surviving ventricular tachycardia (VT) and fibrillation (VF) on admission from 2002 to 2016 were included and stratified according to sex differences by propensity score matching. The primary prognostic end-point was all-cause mortality at 30 months. Secondary end-points were all-cause mortality at 30 days, at index hospitalisation, after discharge, the composite of recurrent ventricular tachyarrhythmias and appropriate implantable cardioverter defibrillator (ICD) therapies, and finally rehospitalisation related to ventricular tachyarrhythmias., Results: A total of 784 (392 males and 392 females) matched patients was included. The rate of VT and VF was similar in both groups (VT: male 65% vs female 62%; VF: male 35% vs female 38%). Male sex was independently associated with the primary end-point of all-cause mortality at 30 months (31% vs 23%; hazard ratio (HR) = 1.432; 95% confidence interval (CI) 1.089-1.883; P = 0.010) as well as with the secondary end-point of all-cause mortality at index hospitalisation (mortality rate 31% vs 23%; log-rank P = 0.010; HR = 1.432; 95% CI 1.089-1.883; P = 0.010; mortality rate 10% vs 15%; HR = 1.685; 95% CI 1.117-2.542; P = 0.013). No differences in further secondary end-points were found. Sex differences of the primary end-point were predominantly observed in patients with VT at index (mortality rate 28% versus 20%; HR = 1.512; 95% CI 1.040-2.189; P = 0.028), without an ICD and with left ventricular ejection fraction ≥35% (log-rank values, P < 0.05)., Conclusion: Males presenting with ventricular tachyarrhythmias on admission were associated with higher all-cause mortality at 30 months and all-cause mortality at index hospitalisation., (© 2018 Royal Australasian College of Physicians.)

Purpose: To evaluate the influence of gestational age on induction of labour in nulliparous women., Material and Methods: This historical cohort study analyzed inductions of labour in low-risk nulliparous women. Therefore the collective was divided into 3 groups (group 1: 40+0 to 40+6 weeks of gestation, group 2: 41+0 to 41+3 weeks of gestation, group 3:>41+3 weeks of gestation). The primary outcome measure was the caesarean section rate., Results: The caesarean section rate was not different among the 3 groups (p=0.4036). The impact of gestational age on induction in multivariable analysis was not significant. Maternal BMI (p<0.0001), maternal age (p=0.0005) and birth weight (p=0.0151) had an influence on the caesarean section rate. Regarding the secondary outcome measures such as umbilical cord blood pH, Apgar score and postpartal neonatal intensive care unit admission, no statistically significant differences have been revealed among the groups., Conclusion: Timing of labour induction after 40+0 weeks of gestation in a low-risk population of nulliparous women did not influence the caesarean section rate., Competing Interests: Die Autoren geben an, dass kein Interessenkonflikt besteht., (© Georg Thieme Verlag KG Stuttgart · New York.)

Purpose: Induction of labour for small-for-gestational-age (SGA) foetus or intrauterine growth restriction (IUGR) is common, but data are limited. The aim of this trial was therefore to compare labour induction for SGA/IUGR with cases with normal fetal growth beyond the 10 th percentile., Material and Methods: This historical multicentre cohort study included singleton pregnancies at term. Labour induction for SGA/IUGR (IUGR group) was compared with cases of fetal growth beyond the 10 th percentile (control group). Primary outcome measure was caesarean section rate., Results: The caesarean section rate was not different between the 2 groups (27.0 vs. 26.2%, p=0.9154). In the IUGR group, abnormal CTG was more common (30.8 vs. 21.9%, p=0.0214), and fetal blood analyses were conducted more often (2.5 vs. 0.5%, p=0.0261). There were more postpartum transfers to the NICU in the IUGR group (40.0 vs. 12.8%, p<0.0001), too., Conclusion: Induction of labour for fetal growth restriction was not associated with an increased rate of caesarean section., Competing Interests: Die Autoren geben an, dass kein Interessenkonflikt besteht., (© Georg Thieme Verlag KG Stuttgart · New York.)

Background: Several guidelines recommend the risk-adapted monitoring of patients with chronic pancreatitis (CP). However, dedicated risk stratification is widely missing in CP. Elderly-CP (disease onset with 60 or more years of age) may represent a subgroup of CP subjects with a distinct course of disease., Aims: We aimed to investigate the clinical presentation of elderly-CP, and if elderly-CP requires an adapted monitoring., Methods: Seven hundred forty one patients with CP were analyzed in a multicenter (Mannheim/Germany, n = 537; Gießen/Germany, n = 100; Donetsk/Ukraine, n = 104), cross-sectional, retrospective study and classified according to the M-ANNHEIM classification., Results: The frequency of elderly-CP was 20% (148/741). In comparison with non-elderly-CP, elderly-CP was less frequently caused by alcohol and nicotine dependency or genetic mutations. In contrast, the frequency of efferent duct abnormalities (p = 0.009, chi-square test) and idiopathic CP (p < 0.0001, chi-square test) increased significantly. The presence of multiple risk factors was found less frequently in elderly-CP than in non-elderly patients (p < 0.0001; chi-square test). Furthermore, elderly-CP was associated with increased rates of pseudocysts (p = 0.0002; chi-square test), endocrine insufficiency (p = 0.001; chi-square test), and the absence of pain (p = 0.04; chi-square test) in the first year of the disease., Conclusion: In elderly-CP, the course of disease significantly differs from non-elderly-CP. Therefore, individualized monitoring strategies for elderly-CP might be necessary., (© 2019 S. Karger AG, Basel.)

Background: Data regarding the prognostic impact of atrial fibrillation (AF) in patients with electrical storm (ES) is rare., Objectives: This study sought to assess the prognostic impact of AF in patients with ES on mortality, rehospitalization, major adverse cardiovascular events (MACE) and recurrence of ES (ES-R)., Methods: All consecutive implantable cardioverter defibrillator (ICD) patients presenting with ES were included retrospectively from 2002 to 2016. Patients with AF were compared to non-AF patients. The primary prognostic endpoint was all-cause mortality. Secondary endpoints were in-hospital mortality, rehospitalization rates, MACE and ES-R., Results: A total of 87 ES patients with ICD were included and followed up to 2.5 years; 43% suffered from AF. The presence of AF was associated with increased all-cause mortality (47 vs. 29%, log-rank p = 0.052; hazard ratio [HR] 1.969, 95% confidence interval [CI] 0.981-3.952, p = 0.057), which was no longer present after multivariable adjustment for age, diabetes and dilated cardiomyopathy. Furthermore, AF was associated with increased rates of overall rehospitalization (61 vs. 31%, log-rank p = 0.013; HR 2.381, 95% CI 1.247-4.547, p = 0.009), especially due to AF (14 vs. 0%, p = 0.001) and acute heart failure (AHF) (28 vs. 10%, p = 0.018; HR 3.754, 95% CI 1.277-11.038, p = 0.016). Notably, AF was not associated with differences in MACE (55 vs. 37%, log rank p = 0.339) and ES-R (28 vs. 25%, log rank p = 0.704)., Conclusion: In ES patients, presence of AF was univariably associated with increased rates of all-cause mortality at 2.5 years. Furthermore, AF was multivariably associated with overall rehospitalization, especially due to AF and AHF., (© 2019 S. Karger AG, Basel.)

Objective: This study sought to assess the impact of treatment with digitalis on recurrences of ventricular tachyarrhythmias in implantable cardioverter defibrillator (ICD) recipients with atrial fibrillation (AF) and heart failure (HF)., Background: The data regarding outcomes of digitalis therapy in ICD recipients are limited., Methods: A large retrospective registry was used, including consecutive ICD recipients with episodes of ventricular tachyarrhythmia between 2002 and 2016. Patients treated with digitalis were compared to patients without digitalis treatment. The primary prognostic outcome was first recurrence of ventricular tachyarrhythmia at 5 years. Kaplan-Meier and multivariable Cox regression analyses were applied., Results: A total of 394 ICD recipients with AF and/or HF was included (26% with digitalis treatment and 74% without). Digitalis treatment was associated with decreased freedom from recurrent ventricular tachy-arrhythmias (HR = 1.423; 95% CI 1.047-1.934; p = 0.023). Accordingly, digitalis treatment was associated with decreased freedom from appropriate ICD therapies (HR = 1.622; 95% CI 1.166-2.256; p = 0.004) and, moreover, higher rates of rehospitalization (38 vs. 21%; p = 0.001) and all-cause mortality (33 vs. 20%; p = 0.011)., Conclusion: Among ICD recipients suffering from AF and HF, treatment with digitalis was associated with increased rates of recurrent ventricular tachyarrhythmias and ICD therapies. However, the endpoints may also have been driven by interactions between digitalis, AF, and HF., (© 2019 S. Karger AG, Basel.)

Objectives:  The M-ANNHEIM classification of chronic pancreatitis (CP) stratifies degrees of disease severity according to the M-ANNHEIM-Severity-Score. We aimed to demonstrate the clinical usefulness of the M-ANNHEIM-Severity-Score in quantifying and predicting the frequency of pancreatic surgery, and to establish the M-ANNHEIM-Surgery-Score as a simplified system for patient surveillance regarding the demand of pancreatic surgery., Methods:  We performed a retrospective, cross-sectional study with 741 CP patients (Mannheim/Germany, n = 537; Gießen/Germany, n = 100; Donetsk/Ukraine, n = 104) categorized according to the M-ANNHEIM classification., Results:  We observed a significantly higher M-ANNHEIM-Severity-Score in patients that were classified within 7 days preceding pancreatic surgery than in individuals that did not require surgery (p < 0.001, Mann-Whitney-U-test). Using a logistic regression analysis with all variables of the M-ANNHEIM-Severity-Score, we established the M-ANNHEIM-Surgery-Score as a simplified new tool to identify patients that may require surgery. A receiver operating characteristic-analysis revealed a cut-off-value of 9 points within the M-ANNHEIM-Surgery-Score to identify these individuals (sensitivity 78.7 %, specificity 91 %). Based on the M-ANNHEIM-Surgery-Score, we defined three categories for demand of surgery with frequencies of pancreatic operations of 1.6 % (n = 7/440) in the "Baseline-Demand"-category, 7 % (n = 12/172) in the "Low-Demand"-category (p < 0.0001, Chi-square-test, OR 4.6, Confidence Interval (CI) 1.8 - 12), and 54 % (n = 70/129) in the "High-Demand"-category (p < 0.0001, OR 73, CI 32 - 167). Patients that were categorized for the "High-Demand"-category, but were not operated on, had a significantly increased ratio of clinical features that hamper performance of surgery (p < 0.001, Chi-square-test)., Conclusions:  The M-ANNHEIM-Surgery-Score represents a useful tool to monitor patients with CP and to estimate the demand of surgery in CP., Competing Interests: Disclosure The authors report no conflicts of interest in this work., (© Georg Thieme Verlag KG Stuttgart · New York.)

Background The study sought to assess the prognostic impact of acute myocardial infarction ( AMI ) with and without ST -segment-elevation myocardial infarction ( STEMI and NSTEMI ) in patients with ventricular tachyarrhythmias and sudden cardiac arrest ( SCA ) on admission. Methods and Results A large retrospective registry was used including all consecutive patients presenting with ventricular tachycardia ( VT ), fibrillation ( VF ), and sudden cardiac arrest ( SCA ) on admission from 2002 to 2016. AMI versus non- AMI and STEMI versus NSTEMI were compared applying multivariable Cox regression models and propensity-score matching for evaluation of the primary prognostic end point defined as long-term all-cause mortality at 2.5 years. Secondary end points were 30 days all-cause mortality, cardiac death at 24 hours, in hospital death, and recurrent percutaneous coronary intervention (re- PCI ) at 2.5 years. In 2813 unmatched high-risk patients with ventricular tachyarrhythmias and SCA , AMI was present in 29% (10% STEMI , 19% NSTEMI ) with higher rates of VF (54% versus 31%) and SCA (35% versus 26%), whereas VT rates were higher in non- AMI (56% versus 30%) ( P < 0.05). AMI -related VT ≥48 hours was associated with higher mortality (log rank P = 0.001). Multivariable Cox regression models revealed non- AMI (hazard ratio = 1.458; P = 0.001) and NSTEMI (hazard ratio = 1.460; P = 0.036) associated with increasing long-term all-cause mortality at 2.5 years, which was also proven after propensity-score matching (non- AMI versus AMI : 55% versus 43%, log rank P = 0.001, hazard ratio = 1.349; NSTEMI versus STEMI : 45% versus 34%, log rank P = 0.047, hazard ratio = 1.372). Secondary end points including 30 days and in-hospital mortality, as well as re- PCI were higher in non- AMI patients. Conclusions In high-risk patients presenting with ventricular tachyarrhythmias and SCA , non- AMI revealed higher mortality than AMI , respectively NSTEMI than STEMI , alongside AMI -related VT ≥48 hours.

Objectives: The study sought to assess the prognostic impact of type 2 diabetes in patients presenting with ventricular tachyarrhythmias on admission., Background: Data regarding the prognostic outcome of diabetics presenting with ventricular tachyarrhythmias is limited., Methods: A large retrospective registry was used including all consecutive patients presenting with ventricular tachycardia (VT) and fibrillation (VF) on admission from 2002 to 2016. Patients with type 2 diabetes (diabetics) were compared to non-diabetics applying multivariable Cox regression models and propensity-score matching for evaluation of the primary prognostic endpoint of long-term all-cause mortality at 2 years. Secondary prognostic endpoints were cardiac death at 24 h, in-hospital death at index, all-cause mortality at 30 days, all-cause mortality in patients surviving index hospitalization at 2 years (i.e. "after discharge") and rehospitalization due to recurrent ventricular tachyarrhythmias at 2 years., Results: In 2411 unmatched high-risk patients with ventricular tachyarrhythmias, diabetes was present in 25% compared to non-diabetics (75%). Rates of VT (57% vs. 56%) and VF (43% vs. 44%) were comparable in both groups. Multivariable Cox regression models revealed diabetics associated with the primary endpoint of long-term all-cause mortality at 2 years (HR = 1.513; p = 0.001), which was still proven after propensity score matching (46% vs. 33%, log rank p = 0.001; HR = 1.525; p = 0.001). The rates of secondary endpoints were higher for in-hospital death at index, all-cause mortality at 30 days, as well as after discharge, but not for cardiac death at 24 h or rehospitalization due to recurrent ventricular tachyarrhythmias., Conclusion: Presence of type 2 diabetes is independently associated with an increase of all-cause mortality in patients presenting with ventricular tachyarrhythmias on admission.

Objectives: Patients with inflammatory bowel disease (IBD) frequently reveal features of pancreatic inflammation. However, the prevalence of IBD in patients with alcoholic pancreatitis (AP) and nonalcoholic pancreatitis (NAP) has not yet been determined, and the prevalence of IBD in patients with autoimmune pancreatitis (AiP) from Germany is unknown., Aims: Thus, we aimed, first, to determine the prevalence of IBD in AP, NAP, and AiP from a tertiary center in Germany and, second, to characterize patients with AiP and IBD., Methods: We performed a retrospective cross-sectional study to determine the prevalence of IBD in patients with different forms of pancreatitis presenting to our clinic., Results: Compared to the general population and to a control group with viral hepatitis from our clinic, we observed the most significant increase of IBD in patients with AiP (n = 3/28; p < 0.0001 vs. general population, binomial proportion test; p = 0.0112 vs. hepatitis group, Fisher's exact test), followed by a significant increase in subjects with NAP (n = 11/278; p < 0.0001 vs. general population, binomial proportion test; p = 0.0338 vs. hepatitis group, Fisher's exact test). A review of previous studies on the prevalence of IBD among patients with AiP revealed a combined prevalence of 12 % (n = 43/355). Type 2 AiP is significantly more often associated with IBD than type 1 AiP (n = 28/48, 58 % vs. n = 7/129, 5 %; combined patient cohort, p < 10E - 12; Fisher's exact test)., Conclusions: Immune-mediated mechanisms related to IBD may participate in the development of AiP, especially AiP type 2, and may also increase the risk for the development of other forms of pancreatic inflammation., Competing Interests: Disclosure The authors report no conflicts of interest in this work., (© Georg Thieme Verlag KG Stuttgart · New York.)

Background: To comparatively evaluate long-term prognostic values of fibrotic biomarkers galectin-3, gremlin-1 and osteopontin in patients presenting to the emergency department (ED) suspected of acute heart failure (AHF)., Methods: Patients with acute dyspnea or peripheral edema were enrolled in the ED. Biomarkers were measured and added to prognostic models including 11 conventional risk factors plus NT-proBNP assessing state-of-the-art statistics of discrimination, calibration, reclassification and Cox regression analyses. Prognostic outcomes were long-term all-cause mortality (ACM) and AHF-related rehospitalization (AHF-RH) at 1 and 5 years., Results: 401 patients including 122 AHF patients were enrolled (mean age 67 years, males 51%). During 5 years follow-up 129 patients (30%) died and 73 (18%) were re-hospitalized because of AHF. In multivariate analysis, galectin-3 (hazard ratios (HR) range 1.4–1.9; p = 0.03) and osteopontin (HR range 1.2–1.4; p = 0.001) remained associated with ACM overall and in the AHF population at 5 years, whereas gremlin-1 remained associated with AHF-RH at 1 year in AHF patients (HR 1.3; p = 0.002). ACM in whole cohort was best discriminated (AUC = 0.85, p = 0.0001), calibrated and re-classified (NRI + 0.50 to + 0.56, p = 0.0001) by galectin-3, whereas in AHF patients ACM was best discriminated by osteopontin (AUC range: 0.82–0.84, p = 0.0001; NRI + 0.34 to + 0.38, p < 0.1) and AHF-RH at 1 year by gremlin-1 (AUC range: 0.82–0.92, p = 0.0001; NRI + 0.59 to + 0.60, p = 0.006)., Conclusions: A panel of fibrotic biomarkers, including osteopontin, galectin-3 and gremlin-1, might be useful for long term risk-stratification of symptomatic ED patients being suspected of AHF.

Purpose: The purpose of this prospective study was to investigate absolute radiation exposure values and factors that influence radiation exposure of interventionists during CT-guided interventions (CTGIs). To our knowledge, no data exist regarding the radiation dose to which the interventionist is exposed during these procedures., Methods: Absolute radiation dose values from a total of 131 CTGIs were analyzed. Radiation dose values were collected by thermoluminescent dosimeters that were positioned above the lead protection being worn, on the forehead, thyroid, chest, gonads, and right and left hand and foot. The radiation doses were analyzed with respect to the experience level of the person performing the procedure, the degree of difficulty measured on a 4-point Likert scale, the lesion size measured on a 3-point Likert scale, and the CT system used., Results: Median whole-body dose was 12 μSv. With the exception of the forehead, all whole-body radiation doses were statistically significantly lower in CTGIs performed using the modern dual-source CT system compared with the 16-slice multi-detector CT. For CTGIs rated as more complex, the radiation exposure of the radiologist performing the procedure was statistically significantly higher, with the exception of the left hand. A statistically significantly lower median whole-body dose was measured for inexperienced compared with experienced radiologists. However, a few dose measurements of more than 1 mSv were found at the right hand., Conclusions: Radiation exposure measured during CTGIs is low (<50 μSv). Because the radiation dose was higher in more-complex interventions and for 16-slice multi-detector row CT, inexperienced radiologists should focus on less-complex procedures., (Copyright © 2015 American College of Radiology. Published by Elsevier Inc. All rights reserved.)

Background: As a mediator of ECM homeostasis, connective tissue growth factor (CTGF) appears to be involved in adverse structural remodeling processes in the heart. However, the diagnostic and prognostic value of CTGF levels in acute heart failure (AHF) in addition to natriuretic peptide testing has not yet been evaluated., Methods and Results: A total of 212 patients presenting with acute dyspnea and/or peripheral edema to the Emergency Department were evaluated. CTGF and NT-proBNP plasma levels were measured at the initial presentation. All patients were followed up to 1 and 5 years. The first endpoint tested was the diagnostic non-inferiority of combined CTGF plus NT-proBNP compared to NT-proBNP alone for AHF diagnosis. Afterwards, the additional diagnostic value of CTGF plus NT-proBNP was tested. CTGF levels were higher in NYHA class III/IV and AHA/ACC class C/D patients compared to lower class patients (p = 0.04). Patients with HFREF revealed highest CTGF levels (median 93.3 pg/ml, IQR 18.2-972 pg/ml, n = 48) compared to patients with a normal heart function (i.e., without HFREF and HFPEF) (median 25.9, IQR <1-82.2 pg/ml, n = 37) (p < 0.05), followed by patients with HFPEF (median 82.2 pg/ml, IQR 11.5-447 pg/ml, n = 32) as assessed by echocardiography. Finally, CTGF levels were higher in patients with AHF (median 77.3 pg/ml, IQR 22.5-1012 pg/ml, n = 66) compared to those without (p = 0.002). CTGF plus NT-proBNP was non-inferior to NT-proBNP testing alone for AHF diagnosis (AUC difference 0.01, p > 0.05). CTGF plus NT-proBNP improved the diagnostic capacity for AHF (accuracy 82 %, specificity 83 %, positive predictive value 66 %, net reclassification improvement +0.11) compared to NT-proBNP alone (p = 0.0001). CTGF levels were not able to differentiate prognostic outcomes after 1 and 5 years., Conclusions: Additional CTGF measurements might lead to a better discrimination of higher functional and structural heart failure stages and might identify patients of an increased risk for an acute cardiac decompensation.

Background: Multimorbidity and polypharmacy represent a major problem for elderly patients; improvement of medication schemes is important and listing approaches (e.g. Beers list) are considered to be potentially useful., Objectives: The aim of this study was to perform expert consensus validation of the FORTA (Fit fOR The Aged) List, a drug classification combining positive and negative labelling of drugs chronically prescribed to elderly patients., Methods: A two-round Delphi procedure was conducted involving 20 experts, 17 geriatric internists and 3 geriatric psychiatrists from Germany and Austria, evaluating the labels assigned to 190 substances or substance groups. These labels ranged from A (indispensable), B (beneficial), C (questionable) to D (avoid), depending on the state of evidence for safety, efficacy and overall age-appropriateness. The experts were also requested to suggest additional substances and indication areas for assessment and possible inclusion in the FORTA List. A weighted (corrected) consensus coefficient was generated for each substance to reflect (1) agreement with the original label, and (2) distribution among raters' labels., Results: The overall consensus for all items and raters was 92% (corrected). For 54/190 items (28.4%), a unanimous response was achieved as to the original author-based FORTA label choice. Twenty-four substances (12.6%) fell short of the consensus cutoff and were re-evaluated in a second round. This yielded confirmation of 171/190, or 90%, of the original author-based FORTA labels. A total of 35 new substances were also accepted for the FORTA List. Drugs used for dementia and dementia syndromes provoked particular response heterogeneity., Conclusion: The FORTA List now reflects a wider consensus among experts, increasing its validity for clinical use. It represents a tool to improve the quality of drug prescription in older patients by identifying both inappropriate and omitted drugs, and thus overtreatment and undertreatment. The validation of FORTA's impact on clinical endpoints has yielded promising preliminary results, to be corroborated in ongoing larger trials.

Purpose: To assess whether chronic lung disease (CLD) in surviving infants with congenital diaphragmatic hernia (CDH) is associated with lung hypoplasia on the basis of the results of antenatal observed-to-expected fetal lung volume (FLV) ratio measurement at magnetic resonance (MR) imaging., Materials and Methods: The study received approval from the institutional review board, with waiver of informed consent for this retrospective review from patients who had previously given informed consent for prospective studies. The ratio of observed to expected FLV at MR imaging was calculated in 172 fetuses with CDH. At postpartum day 28, the need for supplemental oxygen implicated the diagnosis of CLD. At day 56, patients with CLD were assigned to one of three groups-those with mild, moderate, or severe CLD-according to their demand for oxygen. Logistic regression analysis was used to assess the prognostic value of the individual observed-to-expected FLV ratio for association with postnatal development of CLD., Results: Children with CLD were found to have significantly smaller observed-to-expected FLV ratios at MR imaging than infants without CLD (P < .001). Grading of CLD revealed significant differences in observed-to-expected FLV ratio between patients with mild CLD and those with moderate (P = .012) or severe (P = .007) CLD. For an observed-to-expected FLV ratio of 5%, 99% of patients with CDH developed CLD, compared with less than 5% of fetuses with an observed-to-expected FLV ratio of 50%. Perinatally, development and grade of CLD were further influenced by the need for extracorporeal membrane oxygenation (ECMO) (P < .001) and gestational age at delivery (P = .009)., Conclusion: Manifestation of CLD in surviving infants with CDH is associated with the prenatally determined observed-to-expected FLV ratio. Early neonatal therapeutic decisions can additionally be based on this ratio. Perinatally, ECMO requirement and gestational age at delivery are useful in further improving the estimated probability of CLD.

Background: Sézary syndrome (SS) is defined by the triad of erythroderma, generalized lymphadenopathy and more than 1 000 circulating Sézary cells/μl in the peripheral blood., Patients and Methods: We screened the cutaneous lymphoma registry of our department for SS patients to identify clinical features of SS besides the defining criteria and to correlate them with disease survival., Results: 24 SS patients were analyzed retrospectively. The mean age was 65 years with 62 % male patients. The median follow-up time was 32.5 months with an estimated 5-year overall survival rate of 76 %. All patients complained about itching and presented with palmoplantar keratoderma. 62.5 % had nail involvement, 21 % alopecia, 12.5 % ectropion, 4 % prurigo nodularis, 8 % localized and 8 % generalized skin tumors, including leonine facies. In addition, 33 % had infections and also 33 % had venous thromboembolism. We identified cutaneous tumor cell load as a significant prognostic marker for SS. None of the other parameters were associated with disease specific survival., Conclusions: Clinically SS is characterized by various presentations beyond erythroderma. The cutaneous tumor cell load in SS is strongly associated with outcome and survival. We demonstrate a high risk for venous thromboembolism in SS patients who might benefit from anti-coagulation therapies., (© The Authors | Journal compilation © Blackwell Verlag GmbH, Berlin.)

Introduction: A single nucleotide polymorphism of the factor VII activating protease (FSAP), FSAP Marburg I (rs7080536) has been identified as a risk factor for venous thrombosis, but its clinical role has so far been controversial in part due to small cohort sizes. The aim of the present case-control study was to elucidate the impact of the FSAP Marburg I polymorphism (FSAP-MI) on the development of venous thromboembolic disease (VTE) with other known sequence variations, including Factor V Leiden (rs6025) and Factor II G20210A (rs1799963)., Materials and Methods: The study included 891 patients (312 male and 579 female) with a history of deep venous thrombosis (DVT) and/or pulmonary embolism (PE) and 1283 healthy blood donors with no history of venous thromboembolic disease., Results: We found that besides to the well-established aforementioned sequence variations of FV and Prothrombin, the FSAP Marburg I (FSAP-MI) polymorphism was significantly associated with the development of DVTs (1.65 (1.16-2.34) OR (95% CI)) and recurrent thromboembolic events (DVT and PE) (2.13 (1.35-3.36) OR (95% CI)). Comparing patients displaying one or more events FSAP-MI was still associated with the development of recurrent thromboembolic events (1.64 (1- 2.69) OR (95% CI))., Conclusions: We conclude that FSAP Marburg-I genotyping may be used to determine the risk for thromboembolic disorders in patients with suspected thrombophilia and known DVT or PE., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Background: In Germany little data on the epidemiology and histology of lip cancers are available, as lip cancers are commonly pooled together with head and neck tumors., Patients and Methods: Retrospective analysis of 181 patients with malignant tumors of the lips with respect to gender, location, histology, risk factors and comorbidity., Results: There were 90 women and 91 men with a mean age of 71 years. 98 had a tumor on the upper lip and 83 patients on the lower lip. Tumors of the upper lip showed a slight female preference (61%). In contrast lower lip cancer was more common (64%) in men. Histological analysis revealed that in both regions nodular basal cell carcinomas as well as squamous cell carcinomas (NOS) are the most common subtypes. Vertical tumor thickness of squamous cell carcinomas was in most cases smaller than 6 mm (n = 71) and only in 4 cases was a tumor thickness of >6 mm detected. Altogether, 57% of the patients reported a high to very high sun exposure., Conclusions: In comparison to previous studies we found a weaker preference for women for tumors of the upper lip and also a weaker preference for men for tumors of the lower lip. The causes remain unclear, but could be causally related to an increased life expectancy and/or changed risk profile., (© The Authors • Journal compilation © Blackwell Verlag GmbH, Berlin.)

Background: In a recently published genome-wide association study (GWAS), three single nucleotide polymorphisms (SNPs) (rs2824292, rs1353342, rs12090554) were significantly associated with increased susceptibility for ventricular fibrillation (VF) during acute myocardial infarction (AMI). The association of rs2824292 could be confirmed in a second cohort. Both cohorts were from the Netherlands. We aimed to replicate this association in a German cohort of AMI patients with or without VF., Methods: We included a German cohort of 90 individuals with AMI and VF (cases) and 167 AMI individuals without VF and used Taqman assays for SNP typing., Results: None of the loci showed evidence for a statistically significant association with VF. The observed genotype frequencies of the three loci were in Hardy-Weinberg equilibrium, which essentially excludes genotyping errors., Conclusions: In contrast to the data from the Netherlands, we could not detect a significant association of the rs2824292 locus and risk of VF during AMI in our German cohort. Differences in recruitment and clinical phenotypes between the Dutch and German cohorts may underlie different genotype associations.

We aimed to determine the diagnostic performance of biomarkers in predicting myocardial fibrosis assessed by late gadolinium enhancement (LGE) cardiovascular magnetic resonance imaging (CMR) in patients with hypertrophic cardiomyopathy (HCM). LGE CMR was performed in 40 consecutive patients with HCM. Left and right ventricular parameters, as well as the extent of LGE were determined and correlated to the plasma levels of midregional pro-atrial natriuretic peptide (MR-proANP), midregional pro-adrenomedullin (MR-proADM), carboxy-terminal pro-endothelin-1 (CT-proET-1), carboxy-terminal pro-vasopressin (CT-proAVP), matrix metalloproteinase-9 (MMP-9), tissue inhibitor of metalloproteinase-1 (TIMP-1) and interleukin-8 (IL-8). Myocardial fibrosis was assumed positive, if CMR indicated LGE. LGE was present in 26 of 40 patients with HCM (65%) with variable extent (mean: 14%, range: 1.3-42%). The extent of LGE was positively associated with MR-proANP (r = 0.4; P = 0.01). No correlations were found between LGE and MR-proADM (r = 0.1; P = 0.5), CT-proET-1 (r = 0.07; P = 0.66), CT-proAVP (r = 0.16; P = 0.3), MMP-9 (r = 0.01; P = 0.9), TIMP-1 (r = 0.02; P = 0.85), and IL-8 (r = 0.02; P = 0.89). After adjustment for confounding factors, MR-proANP was the only independent predictor associated with the presence of LGE (P = 0.007) in multivariate analysis. The area under the ROC curve (AUC) indicated good predictive performance (AUC = 0.882) of MR-proANP with respect to LGE. The odds ratio was 1.268 (95% confidence interval 1.066-1.508). The sensitivity of MR-proANP at a cut-off value of 207 pmol/L was 69%, the specificity 94%, the positive predictive value 90% and the negative predictive value 80%. The results imply that MR-proANP serves as a novel marker of myocardial fibrosis assessed by LGE CMR in patients with HCM.

Background: A spinal saddle block can be a safe method for anorectal surgery with a low rate of complications when performed with the right technique. A dreaded complication is the post-dural puncture headache (PDPH), which can be decreased by the use of non-cutting spinal needles. Regrettably, cutting Quincke (Q)-type needles are still widely used for economic reasons. Besides size and design of a spinal needle, the pre-operative time in upright sitting position may also influence the incidence of PDPH after spinal saddle block., Methods: Within 4 months, 363 patients undergoing anorectal surgery in saddle block technique were randomised to receive either a 27-gauge (G) pencil-point (PP) or a 27-G Q spinal needle and were pre-operatively left in upright sitting position for 10 or 30 min, respectively. The incidence of PDPH was assessed 1 week after the operation via a telephone interview., Results: Three hundred sixty three patients (219 males/144 females) were analysed. Fifteen patients (4.1%) developed PDPH. Patients receiving spinal anaesthesia with a Q needle suffered significantly more frequently from PDPH [Q: n = 12 (6.6%) vs. PP: n = 3 (1.7%), p = 0.02], but there was no association between PDPH and pre-operative time in the upright position (p = 0.20)., Conclusions: These data prove that using 27-G PP needles is the method with the fewest side effects caused by spinal saddle block, and suggest that the time spent sitting in the upright position is not clinically relevant.

Unlabelled: The P-Selectin Gene Polymorphism Val168Met., Aims: Ventricular fibrillation (VF) in the setting of acute myocardial infarction (AMI) is the leading cause of sudden cardiac death (SCD). Family history of SCD is described as risk factor for primary VF during acute AMI. Genetic factors may be associated with primary VF. We examined polymorphisms in genes related to the activation and adhesion of blood platelets in patients with and without VF in the setting of AMI and among healthy controls., Methods: Two hundred and forty patients with a history of AMI and 475 healthy controls were studied. Seventy-three patients (30%) had primary VF during AMI. By using PCR techniques with sequence-specific primers (PCR-SSP), we genotyped 5 single nucleotide polymorphisms (SNPs) in P-selectin (SELP) (V168M, S290N, N592D, V599L, T715P), 2 SNPs (M62I, S273F) in P-selectin glycoprotein ligand-1 (SELPLG), 5 SNPs in CD40LG (-3459A>G, -122A>C, -123A>C, 148T>C, intr4-13T>C), the H558R SNP in SCN5A, and rs2106261 in ZFHX3. In addition, length polymorphisms in SELPLG (36bp-tandem repeat) and CD40LG (CA-repeat) were genotyped by PCR methods. Results were evaluated by 2-sided t-tests, chi-square tests, and logistic regression analysis., Results: None of the gene polymorphisms showed significant differences between AMI patients and healthy controls. Among patients with a history of VF, however, the SELP 168M variant showed a significantly higher prevalence (14/73 patients; 19.2%) as compared with patients without VF (13/167 patients; 7.8%; P < 0.01). This association remained significant in a logistic regression analysis after adjustment for age and gender (P = 0.013; odds ratio 2.8; 95% confidence interval 1.2-6.3)., Conclusions: This is the first description of an association of the SELP gene variant 168M with primary VF during acute MI. This variant may be a candidate polymorphism for evaluating the susceptibility for VF in the setting of acute MI., (© 2010 Wiley Periodicals, Inc.)

Purpose: Spinal saddle block represents nearly the ideal anaesthesia technique for anorectal surgery. Post-dural puncture headache (PDPH) is a dreaded complication but can be decreased by the use of non-cutting spinal needles to rates less than 1%. Though, cutting Quincke type needles are still widely used for economic reasons, leading to a higher rate of PDPH. We performed this study to demonstrate a reduction of PDPH by the use of very small 29-G compared with commonly used 25-G Quincke type spinal needles., Methods: Two hundred sixteen adult patients (male/female, 19-83 years, ASA status I-III) were randomised 1:1 to groups, in which either a 25-G or a 29-G Quincke type spinal needle was used for a spinal saddle block. The incidence of PDPH was assessed during 1 week after surgery., Results: Thirty-nine of 216 patients developed PDPH but there was no difference between the two needle sizes (25-G, n = 18/106 vs. 29-G, n = 21/110, p = 0.6870). Women suffered significantly more from PDPH than men (23/86 vs. 16/130, p = 0.0069). Ambulatory patients had a later onset of PDPH than in-patients (24 h [0.5-72] vs. 2 h [0.2-96], p = 0.0002) and the headache was more severe in these patients (NRS 7 [2-10] vs. NRS 3 [1-8], p = 0.0009)., Conclusions: The use of 29-G compared with 25-G Quincke needles led to no reduction of PDPH and is considerably higher compared with data from pencil-point needles. The use of non-cutting or pencil-point spinal needles should become the standard for performing spinal saddle block.

Objective: The objective of our study was to evaluate the influence of endogenous and exogenous risk factors on the rate of nondiagnostic examinations of the calves in peripheral bolus-chase MR angiography (MRA)., Subjects and Methods: Peripheral bolus-chase MRA runoff studies in 177 patients with peripheral arterial occlusive disease (PAOD) were retrospectively assessed with regard to the rate of nondiagnostic image quality due to substantial venous overlay in the calf arteries requiring repeated MRA examinations. Logistic regression was used to analyze the rate of nondiagnostic MRA examinations as a function of several endogenous and exogenous risk factors and of the stage of PAOD. To probe the retrospective data, 22 consecutive patients were prospectively included and underwent a standard peripheral MRA examination if the probability of a nondiagnostic examination was less than 50% based on the results of logistic regression; otherwise, a hybrid MRA examination was ordered., Results: Nondiagnostic image quality of the calf arteries was found in 53 patients (30%). The incidence increased with each stage of PAOD up to 39% for stage IV. For each increase in the stage of PAOD, the probability of nondiagnostic image quality increased by a factor of 1.5561 (p = 0.0024). With an increasing number of risk factors, a significantly (p = 0.0074) higher rate of nondiagnostic images was found., Conclusion: Based on the retrospective statistical analysis of PAOD stages and risk factors, selected patients can be triaged to undergo a specific hybrid MRA technique and thus circumvent the occurrence of nondiagnostic images and the need for repeated MRA examinations.

Objective: Recurrent thromboembolic events may occur after termination of anticoagulant therapy for acute venous thromboembolism (VTE) using oral direct thrombin inhibitor ximelagatran., Methods: Patients with VTE recruited at the German study centres were followed-up for an additional 18 months, treated initially with 2x36 mg ximelagatran daily or with enoxaparin/warfarin over 6 months (THRIVE Treatment study) and 2x24 mg ximelagatran daily or placebo over 18 months (THRIVE III study). Recurrent VTE and the combined outcome events consisting of recurrent VTE, other thrombotic complication, major bleeding and mortality were analysed., Results: In the THRIVE Treatment study, no patient suffered from a recurrent VTE, but 1 patient randomised to enoxaparin/warfarin experienced major bleeding. During follow-up, 4/32 and 3/32 patients initially randomised to ximelagatran and enoxaparin/warfarin developed recurrent VTE (p=0.7024). No major bleed occurred. One patient in each group died. The incidences of the combined outcome events were not different (p=0.9326). In the THRIVE III study, 0/9 versus 5/14 patients randomised to ximelagatran and placebo developed recurrent VTE including 1 fatal pulmonary embolism (p=0.0501). During follow-up, 3/9 and no patients initially randomised to ximelagatran and placebo developed recurrent VTE. One and 3 other outcome events occurred in patients initially randomised to ximelagatran or placebo. During follow-up, recurrent VTE (p=0.6893) and combined outcome events (p=0.3642) were not different between the groups., Conclusion: The results of the follow-up studies suggest that thromboembolic events may re-occur in patients with acute VTE after termination of treatment with both vitamin K-antagonists and ximelagatran.