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Aircraft structures experience various kinds of loads over their entire lifetime, typically leading to fatigue, and ultimately structural failure. To avoid structural failure during operation, the ...

Zusammenfassung Hintergrund Die Sarkoidose ist eine granulomatöse Multisystemerkrankung unklarer Ätiologie und stellt durch ihre relative Seltenheit sowie ihr heterogenes Krankheitsbild eine klinisch diagnostische Herausforderung dar. Wir gehen der Frage nach, ob bei oberflächlich sichtbaren Läsionen der Haut die Differenzialdiagnose einer Sarkoidose in Betracht gezogen wird und welche systemischen Manifestationen vorliegen. Material und Methoden Im Rahmen unserer explorativen retrospektiven Untersuchung wurden in einem Zeitraum von 8 Jahren insgesamt 32 Patienten mit einer Sarkoidose der Haut identifiziert und die Daten analysiert. Ergebnisse und Schlussfolgerung Wir konnten in unserer Erhebung zeigen, dass die Differenzialdiagnose einer Sarkoidose durch die dermatologischen Kollegen in vielen Fällen schon vor der Biopsie in Erwägung gezogen wurde (71,8 %); dies war in einer vorangegangenen Studie an Patienten in der HNO-Heilkunde nicht der Fall. Bei insgesamt 90,6 % der Patienten wurde dann sogar die Erstdiagnose durch die anschließende Hautbiopsie gestellt. Die Sarkoidose der Haut im Kopf-Hals-Bereich kann durchaus auch dem HNO-Arzt begegnen; in unserer Erhebung handelt es sich sogar um die zweithäufigste kutane Manifestation. Nach erfolgter Biopsie (Goldstandard) ist die Suche nach weiteren möglichen Organmanifestationen besonders wichtig (bspw. Lunge, Herz), um die Komplikationen eines möglichen chronischen Krankheitsverlaufs (u. a. Herzrhythmusstörungen, Lungenfibrose) frühzeitig zu erkennen und zu behandeln.

BACKGROUND The effects of adrenaline on cerebral blood vessels during cardiopulmonary resuscitation (CPR) are not well understood. We developed an extracorporeal CPR model that maintains constant low systemic blood flow while allowing adrenaline-associated effects on cerebral vasculature to be assessed at different mean arterial pressure (MAP) levels independently of the effects on systemic blood flow. METHODS After eight minutes of cardiac arrest, low-flow extracorporeal life support (ECLS) (30 ml/kg/min) was started in fourteen pigs. After ten minutes, continuous adrenaline administration was started to achieve MAP values of 40 (n = 7) or 60 mmHg (n = 7). Measurements included intracranial pressure (ICP), cerebral perfusion pressure (CePP), laser-Doppler-derived regional cerebral blood flow (CBF), cerebral regional oxygen saturation (rSO2), brain tissue oxygen tension (PbtO2) and extracellular cerebral metabolites assessed by cerebral microdialysis. RESULTS During ECLS without adrenaline, regional CBF increased by only 5% (25th to 75th percentile: -3 to 14; p = 0.2642) and PbtO2 by 6% (0-15; p = 0.0073) despite a significant increase in MAP to 28 mmHg (25-30; p

INTRODUCTION/AIMS Glucocorticoid-induced osteoporosis with vertebral fractures is frequent in patients with Duchenne muscular dystrophy (DMD). In this study, we evaluated the effects of oral bisphosphonate (BP) therapy on the prevalence and severity of vertebral fractures by vertebral morphometry assessment. METHODS We reviewed the records and radiographs of patients with DMD who had been treated with oral BP (weekly alendronate) and had undergone routine spine radiographic monitoring for glucocorticoid-induced osteoporosis at Cincinnati Children's Hospital Medical Center between 2010 and 2017. Study outcomes were thoracic and lumbar vertebral fracture prevalence and severity, assessed by Genant semiquantitative grading of vertebral morphometry, for up to 5 years of treatment. RESULTS Fifty-two patients (median age, 11.8 years; 88% prepubertal; 31% nonambulatory) had been treated with long-term glucocorticoids (median duration, 4.7 years at BP start). Most patients (75%) had mild vertebral height loss or fractures (Genant grade = 0 or 1) at baseline. The prevalence of vertebral fractures at each year of treatment was not statistically different from that at baseline (P = .08-1.00). Serial radiographs showed no longitudinal change in severity by Genant grade in most vertebrae (64%-80%). Improvement in vertebral fracture grade was observed in some patients. DISCUSSION We observed stable prevalence of vertebral fractures and no change in severity by Genant grade in most vertebrae for up to 5 years of treatment. Oral BP may mitigate development or progression of vertebral fractures and be beneficial for secondary prevention of glucocorticoid-induced osteoporosis in this population.

BACKGROUND: A single high-sensitive cardiac troponin (hs-cTn) can be used to rule-out acute myocardial infarction (MI) in patients presenting >3 hours (3 h) after chest pain onset to the emergency department. This study aimed to investigate the safety of ruling-out MI in early presenters with chest pain ≤3 h using a single hs-cTnI at admission.METHODS: We prospectively enrolled patients presenting with chest pain suggestive of MI. Hs-cTnI (Siemens ADVIA Centaur TNIH, Limit of detection: 2.2 ng/L) was measured at admission. Two physicians adjudicated final diagnosis. A diagnostic cut-off value 3 h).RESULTS: We included 1370 patients with available admission hs-cTnI results: median (Q1-Q3) age 65 (52-74), female sex: 43%, previous MI: 22%. We confirmed MI in 118 (8.6%) patients. Overall, 470 (34%) patients were classified as early, 770 (56%) as late presenters, and 130 (9%) patients had unknown onset. When applying the diagnostic cut-off value, MI was correctly ruled-out at admission in 370 (27%) patients: 134 (29%) early presenters, 206 (27%) late presenters and 30 (23%) patients with unknown onset. This resulted in an overall negative predictive value of 100% (95% CI: 99.0-100%), with both 100% (97.3-100%) for early and 100% (98.2-100%) for late presenters, respectively. Sensitivity was similarly high in the two groups.CONCLUSION: MI could be safely ruled-out in all patients presenting with chest pain ≤3 h when using a single hs-cTnI value TRIAL REGISTRATION NUMBER: NCT03634384.

Background. Chronic hepatitis C virus (HCV) infection is characterized by activation of natural killer (NK) cells. Here, we asked whether HCV elimination by sofosbuvir-based direct-acting antivirals (DAAs) and the addition of ribavirin (RBV) improve NK cell function in liver transplant (LTx) recipients. Methods. We analyzed NK cell degranulation and interferon (IFN)γ-response along with STAT1 and STAT4 phosphorylation in 29 HCV-infected LTx recipients and 17 HCV-infected patients during DAA treatment. Results. Compared with uninfected LTx recipients, NK cells from HCV-infected LTx recipients were polarized toward cytotoxicity with increased CD107a-degranulation (10.1% versus 14.6%; P = 0.0263) and reduced capacity to produce IFNγ (43.0% versus 26.7%; P = 0.0002). The altered phenotype of NK cells in HCV-infected LTx recipients was accompanied by increased STAT1 (44.6% versus 87.4%; P < 0.0001) and STAT1 phosphorylation (0.7% versus 8.9%; P = 0.0005) compared with pSTAT4 IFNα-induction (29.9% versus 17.6%; P = 0.0014). Successful DAA therapy did not affect CD107a-degranulation but decreased STAT1. RBV cotreatment with DAA therapy for HCV increased CD56Bright NK cell IFNγ-responses in LTx recipients (70.9% versus 89.2%; P = 0.002), and this correlated to an increase in the inducibility of pSTAT4 (MFI 157 versus 173; P = 0.0002). Conclusions. RBV cotreatment of HCV infection improved pSTAT4-dependent IFNγ-production in NK cells. This is relevant especially for immunocompromised patients such as LTx recipients or patients with end-stage liver disease.

Factors affecting outcomes in liver transplant (LTx) recipients with hepatocellular carcinoma (HCC) and hepatitis C viral (HCV) infection include the choice of immunosuppression. Here, we analyzed the HCV+ subgroup of patients from the randomized controlled, international SiLVER Study. We performed a post hoc analysis of 166 HCV+ SiLVER Study patients regarding HCC outcome after LTx. Control patients (group A: n=88) received mTOR inhibitor (mTORi)-free, calcineurin inhibitor (CNI)-based versus sirolimus-based immunosuppression (group B: n=78). We found no significant difference regarding HCV-RNA titers between group A and B. Since no effect in group B could be due to variable sirolimus dosing, we split group B into patients receiving sirolimus-based immunosuppression+CNIs for >50% (B1; n=44) or

Background A patent foramen ovale (PFO) has been associated with embolic strokes and transient ischemic attacks (TIAs). Catheter closure of PFO is effective in preventing recurrent events. Residual shunts and procedure or device related complications can occur, including atrial fibrillation and thrombus formation . This study examines the initial experience with a new PFO closure device, the IrisFIT PFO-Occluder (Lifetech Scientific, Shenzhen, China). Methods 95 patients with indications for PFO closure underwent percutaneous closure with the IrisFIT PFO-Occluder. The primary endpoint was the rate of accurate device placement with no/small residual shunt at 3 or 6 months follow-up. All patients underwent transoesophageal echocardiography (TEE) after 1 to 6 months. In case of a residual shunt, an additional TEE was performed after 12 months. Clinical follow-up was performed up to a mean of 33.1 ± 3.6 months. Results The device was successfully implanted in 95 (100%) patients with no relevant procedural complications. At final TEE follow-up (7.6 ± 3.9 months) the effective closure rate was 96.8% with 1 moderate and 2 large residual shunts. There were 8 cases of new onset atrial fibrillation and 2 TIAs. There were no cases of device embolization or erosion. Conclusion The IrisFIT occluder is a new PFO closure device with several advantages compared to other devices. In this small study cohort , technical success rate, closure rate and adverse event rate were comparable to other devices. The rate of new onset atrial fibrillation was higher in comparison to other studies and warrants further investigation.

Objectives To identify published economic evaluations of interventions aimed at preventing, diagnosing, or treating food allergies in children. Methods We examined economic evaluations published from 2000 to 2019. Data analyzed included: food allergy type, study population/setting, intervention/comparator, and economic evaluation details. Quality assessment used reporting and economic modeling checklists. Two reviewers simultaneously undertook article screening, data extraction, and quality assessment. Results 17 studies were included: 8 peanut allergy (PA) studies, 8 cow’s milk allergy (CMA) studies, and 1 egg allergy (EA) study. All PA studies reported incremental costs per quality-adjusted life-year gained for diagnostic strategies, management pathways for peanut exposure, and immunotherapies. Immunotherapies rendered inconsistent cost-effectiveness results. CMA studies reported costs per symptom-free day or probability of developing CMA tolerance. Cost-effectiveness of extensively hydrolyzed casein formula for CMA treatment was consistently demonstrated. Early introduction of cooked egg in first year of life dominated all EA prevention strategies. Quality assessment showed average noncompliance for 3.5 items/study (range 0-11) for modeling methods and 3.4 items/study (range 0-8) for reporting quality. Key quality concerns included limited justification for model choice, evidence base for model parameters, source of utility values, and representation of uncertainty. Conclusion Recent cost-effectiveness literature of interventions in PA, CMA, and EA is limited and diverse. Interventions for diagnosis and treatment of CMA and prevention of EA were generally cost-effective; however, results for PA were variable and dependent on effectiveness and utility values used. There is a need to expand economic evaluation of interventions for childhood food allergy and to improve methods and reporting.

Register-based studies indicate a possible association of monoclonal gammopathy of undetermined significance (MGUS) and prostate cancer (PCa). Aim of the present study was to investigate the relationship between MGUS and PCa considering potentially shared risk factors. Data from the prospective population-based Heinz Nixdorf Recall cohort study of 2.385 men (age 45–85) were analyzed. MGUS was determined at three points in time; cases of cancer were assessed annually. Potentially shared risk factors were assessed at baseline. Hazard ratios (HR), adjusted for age and educational attainment, and corresponding 95%-confidence intervals (95%-CI) were calculated. 157 cases of MGUS and 143 incident cases of PCa were detected. Of 19 participants diagnosed with both, MGUS and incident PCa, only in one case MGUS did not clearly occur before PCa. MGUS was associated with PCa presenting a HR of 2.00 (95%-CI: 1.23–3.25). Stratified by isotype, IgM-MGUS showed the strongest association with PCa. There was no relevant change of the effect estimate when adjusting for potentially shared risk factors. We were able to give supporting evidence for an association between MGUS and PCa and pointed out its temporality. There was no indication that the observed association is due to shared risk factors. The present study indicated that different isotypes of MGUS differ in the strength of the effect on PCa-risk. Based on these findings, future studies investigating the pathophysiological background of the association will be needed.

Infection represents probably the most challenging complication in shoulder arthroplasty and all other surgical procedures of the shoulder. A deep infection of the shoulder is often combined with a destruction of the joint and a loss of function. In many cases the arthroplasty is the last resort for these patients to obtain a satisfactory function. The objective of this study was to determine outcome data on microbiota and clinical results of a two-stage shoulder arthroplasty procedure after deep infection of the shoulder. Twenty-six patients with a deep shoulder infection after arthroplasty, osteosynthesis, or rotator-cuff repair were included, while two patients had an empyema without prior surgery. All underwent initial surgical debridement with implantation of an antibiotic-loaded spacer, followed by postoperative systemic antibiotics. The patients obtained definitive shoulder arthroplasty in a second surgery. None of the patients had to undergo more than two surgeries before the arthroplasty. The follow-up analysis including microbiota results, complication rates, and functional outcomes could be determined after at least 1 year in 60% of patients (n = 16). The most frequently detected microorganisms were S. epidermidis (31%, n = 10) and Cutibacterium acnes (19%, n = 6). In 28% (n = 9) of cases multi-drug resistant bacteria were detected and in 35% (n = 8) of cases more than one microorganism was found. The overall revision rate was 42%, 11 of 26 patients, in the first 8 weeks after arthroplasty. Reasons for revision were joint dislocations in 23% (n = 6), 15% (n = 4) postoperative hematomas, one (4%) re-infection and one (4%) periprosthetic fracture. At follow-up after 19.3 ± 5.5 months postoperatively, a mean abduction of 113.4°, anteversion of 122.8° and external rotation of 14° was found, with an average age and gender-adjusted Constant Score of the affected shoulder of 63. The subjects’ pain and impairment in normal life measured by a questionnaire with school grades were significantly reduced (p

Aims An accelerated diagnostic algorithm for ruling-in or ruling-out myocardial infarction (MI) after 1 hour (1 h) has recently been derived and internally validated for the Siemens ADVIA Centaur TNIH assay. We aimed to validate the diagnostic performance of the TNIH 0 h/1 h algorithm ad modum Boeddinghaus in a Danish cohort. Methods and results Patients with chest pain suggestive of MI were prospectively enrolled. High-sensitive troponin I (TNIH) was measured at admission (0 h) and after 30 minutes (30 m), 1 h, and 3 hours (3 h). We externally validated the TNIH 0 h/1 h algorithm ad modum Boeddinghaus in Danish patients. Moreover, we applied the algorithm using the second TNIH measurement at 30 m instead of 1 h. We enrolled 1003 patients: median (Q1–Q3) age 64 (52–74) years, 42% female, and 23% with previous MI. Myocardial infarction was the final diagnosis in 9% of patients. Median (Q1–Q3) times from admission to 30 m and 1 h blood draw were 35 min (30–37 min) and 67 min (62–75 min), respectively. Using the 0 h and 1 h results, 468 (47%) patients were assigned to rule-out, 104 (10%) to rule-in, and 431 (43%) to the observational zone. This resulted in a negative predictive value of 100% (95% confidence interval: 99.2–100%), sensitivity of 100% (95.9–100%), positive predictive value of 79.8 (70.8–87.0%), and specificity of 97.7% (96.5–98.6%). The diagnostic performance after 30 m was similar. Conclusions The TNIH 0 h/1 h algorithm ad modum Boeddinghaus performed excellently for rule-out of MI in a Danish cohort. The Boeddinghaus algorithm also performed excellently after only 30 m. Trial registration number NCT03634384. Trial registry name and URL Rapid Use of High-Sensitive Cardiac Troponin I for Ruling-in and Ruling-out Acute Myocardial Infarction (RACING-MI), https://clinicaltrials.gov/ct2/show/NCT03634384.

Purpose To determine risk factors for coronavirus disease 2019 (COVID-19) in healthcare workers (HCWs), characterize symptoms, and evaluate preventive measures against SARS-CoV-2 spread in hospitals. Methods In a cross-sectional study conducted between May 27 and August 12, 2020, after the first wave of the COVID-19 pandemic, we obtained serological, epidemiological, occupational as well as COVID-19-related data at a quaternary care, multicenter hospital in Munich, Germany. Results 7554 HCWs participated, 2.2% of whom tested positive for anti-SARS-CoV-2 antibodies. Multivariate analysis revealed increased COVID-19 risk for nurses (3.1% seropositivity, 95% CI 2.5–3.9%, p = 0.012), staff working on COVID-19 units (4.6% seropositivity, 95% CI 3.2–6.5%, p = 0.032), males (2.4% seropositivity, 95% CI 1.8–3.2%, p = 0.019), and HCWs reporting high-risk exposures to infected patients (5.5% seropositivity, 95% CI 4.0–7.5%, p = 0.0022) or outside of work (12.0% seropositivity, 95% CI 8.0–17.4%, p p = 0.00018) and the symptom taste disorder was strongly associated with COVID-19 (29.8% seropositivity, 95% CI 24.3–35.8%, p Conclusion Awareness of the identified COVID-19 risk factors and successful surveillance strategies are key to protecting HCWs against SARS-CoV-2, especially in settings with limited vaccination capacities or reduced vaccine efficacy.

One of the major obstacles preventing successful percutaneous pulmonary valve implantation (PPVI) is related to the close proximity of coronary artery branches to the expected landing zone. The aim of this study was to assess the frequency of coronary artery anomalies (CAAs) especially those associated with major coronary branches crossing the right ventricular outflow tract (RVOT) and to describe their relevance for the feasibility of percutaneous pulmonary valve implantation (PPVI). In our retrospective single-center study 90 patients were evaluated who underwent invasive testing for PPVI in our institution from 1/2010 to 1/2020. CAAs were identified in seven patients (8%) associated with major branches crossing the RVOT due to origin of the left anterior descending (LAD) or a single coronary artery from the right aortic sinus. In 5/7 patients with CAAs balloon testing of the RVOT and selective coronary angiographies revealed a sufficiently large landing zone distal to the coronary artery branch. While unfavorable RVOT dimensions prevented PPVI in one, PPVI was performed successfully in the remaining four patients. The relatively short landing zone required application of the “folded” melody technique in two patients. All patients are doing well (mean follow-up 3 years). CAAs associated with major coronary branches crossing the RVOT can be expected in about 8% of patients who are potential candidates for PPVI. Since the LAD crossed the RVOT below the plane of the pulmonary valve successful distal implantation of the valve was possible in 4/7 patients. Therefore these coronary anomalies should not be considered as primary contraindications for PPVI.

Aim Microanatomical evaluation of cochlear implant (CI) patients to identify anatomical risk factors for a scalar translocation. Methods CI patients with both a regular scala tympani spiralization (group A) and a scalar translocation (group B) were identified via postoperative flat-detector computed tomography (FD-CT). Then, the corresponding preoperative multislice computed tomography (MS-CT) and postoperative FD-CT datasets were assessed: First, the cochleae were separated in 6 segments of 45° each. Next, quantitative (cochlea height, length, depth, cochlear duct diameter [CD] per segment; percentual tapering of the CD per segment named cochlear geometry index [CGI]) and qualitative (identifiability of the CI model; CI-integrity; intracochlear array position) parameters were evaluated and compared for both groups. Receiver-operating-characteristics (ROC) analysis was performed for the CGI. Results In total, 40 preoperative MS-CT and postoperative FD-CT datasets (nA = 20; nB = 20) were analysed. Model “CI 512” was successfully identified and CI-integrity has been confirmed in all cases. Quantitative analysis showed a significant difference of both the CD at 0° (CD A 0°= 2.06 ± 0.23 mm; CDB 0°= 2.19 ± 0.18 mm; p0°= 0.04) and the CGI of the first segment (CGIA 0° -45°= 18.87 ± 6.04%; CGIB 0°-45°= 28.89 ± 8.58%; p0°-45°= 0.0001). For all other 5 cochlear segments there was no significant difference of CD and CGI; there was no significant difference of external cochlea diameters. The area under the curve (AUC) of the CGI0-45° was 0.864 with 24.50° as the optimal cut-off value to discriminate patients with a scala tympani spiralization and a scalar translocation. CGI0-45° of > 24.50° allowed the correct identification of 85% of patients with a scalar translocation. Conclusion CI insertion trauma is associated with a significantly higher narrowing of the proximal basal cochlea turn (BCT). The CGI as percentual tapering of the BCT turned out as reliable, clinically applicable parameter for identification of patients with an increased risk for a scalar translocation.

The publication of a selection of Paul John Eakin’s essays on life writing in the new Routledge Auto|Biography Studies series represents a landmark in the history of this immensely fertile genre. T...

Although emotions play an important role in human behavior and knowledge studies, knowledge management (KM) research considers them from specific angles and, to date, has lacked a comprehensive understanding of the emotions dominating KM. To offer a holistic view, this study investigates the presence of emotions in KM publications by applying a sentiment analysis. The authors present a sentiment dictionary tailored to KM, apply it to KM publications to determine where and how emotions occur, and categorize them on an emotion scale. The considerable amount of positive and negative emotions expressed in KM studies prove their relevance to and dominance in KM. There is high term diversity but also a need to consolidate terms and emotion categories in KM. This study's results provide new insights into the relevance of emotions in KM research, while practitioners can use this method to detect emotion-laden language and successfully implement KM initiatives.

Objective This study aimed to provide an overview of the extent to which women with endometriosis are informed about, interested in, and make use of CAM, and to evaluate which of the methods are most often applied. Study Design A retrospective, two-center cohort study was conducted using a validated questionnaire among women with laparoscopically confirmed endometriosis at two urban teaching hospitals, certified as endometriosis centres. Results A total of 592 patients were included in the study and received the questionnaire; 114 (19.3 %) were included in the data analysis. Most of the women were not receiving hormone therapy at the time of the study (n = 60, 52.6 %). Most (n = 75, 65.8 %) were interested in CAM, but only a minority (n = 12, 10.5 %) had detailed knowledge about it. A total of 81 patients (71.1 %) had used at least one CAM method for disease management; the five most frequently used CAM methods were exercise (n = 55, 48.2 %), vitamins (n = 40, 35.1 %), yoga (n = 38, 33.3 %), homeopathy (n = 32, 28.1 %), and trace elements (n = 27, 23.7 %). Conclusions In our study population, women with endometriosis are strongly interested in using CAM, but have only limited information about it. Nevertheless, a majority of the patients had used at least one CAM method to relieve symptoms associated with the disease and the most often used was exercise.

Purpose The aim of this study was to investigate the feasibility and reliability of transcutaneous ultrasound for the detection of complications after cochlear implantation. Methods In a single center retrospective cohort study, 115 consecutive cases of suspected complications after cochlear implantation (intervention group) were examined. The rate of pathologic ultrasound findings for specific leading symptoms and diagnoses was compared to a control group comprising twenty consecutive cochlear implants in symptom-free patients. Results Diagnostic ultrasound showed distinctly more pathologic findings in the intervention group (n = 67; 58.3%; p n = 1; 5%). Ultrasound revealed significantly more pathologic findings in haematoma or seroma around the implant (n = 17; 100%; p ϕ = 0.94) and magnet dislocation (n = 44; 97.7%; p ϕ = 0.92) confirmed by a strong effect. Ultrasound examination showed a medium to high effect size in patients presenting with local infections (n = 3; 21.4%; p = 0.283; ϕ = 0.25) and skin flap oedema (n = 2; 50%; p = 0.061; ϕ = 0.51). In contrast, ultrasound examinations displayed a low effect size in undefined cephalgia (0%; p = 0.444; ϕ = 0.17) and device malfunction or failure (0%; p > 0.999; ϕ = 0.13). Conclusion Transcutaneous ultrasound can be advocated as a feasible and effective method in the diagnostic work-up of magnet dislocation and haematoma or seroma around the implant following cochlear implantation. Contrary, ultrasound findings can be expected to be inconspicuous in patients presenting with undefined cephalgia and device malfunction or failure.

The organization and operation of clinical trials have become increasingly complex requiring the coordination of a well-trained workforce to ensure that complicated protocols yield valid results that will advance human health. We hypothesized that formal education in clinical research is equivalent to a number of years of work experience as a clinical research professional in terms of self-perceived clinical research competence. Using REDCap, we conducted a survey of students and recent graduates from academic programs in clinical research in the USA using the CICRP index that consists of 20 clinical research core competencies. We compared the responses of recent graduates to CRCs wording in the USA and Canada in various research settings who responded to a similar survey conducted by the Joint Task Force and to experienced CRCs working at research-intensive CTSA hubs and their affiliated hospitals who were surveyed as part of the NIH funded DIAMOND project. We found that the degree of self-perceived competence to perform advanced core competencies such as those related to regulatory affairs among new graduates of formal academic programs without research experience to be equivalent to as many as five years of on-the-job-training in a research-intensive CTSA setting and more than ten years of experience in less research-intensive community settings. These findings suggest that scores on both forms of the CICRP differentiate CRCs according to formal education in clinical research, years of experience as a CRC and type of research setting in which they work. Further, the self-perceived competency assessed by CICRP acquired by completing an academic program in clinical research is equivalent to years of work experience.

A 64-year-old female patient presented with otalgia and hearing loss in the right ear. On otoscopy, the right tympanic membrane was highly vascularized and bulged into the anteroinferior quadrant. High-resolution computed tomography revealed an osteolytic lesion with occupation of the hypotympanum extending into the petrous apex and right parapharyngeal space as well as infiltration of the wall of the right internal carotid artery. MRI strengthened the suspicion of a jugulotympanic paraganglioma. The biopsy material obtained through exploratory tympanotomy was assessed as a low-grade polymorphic adenocarcinoma. The tumor was treated with definitive chemoradiotherapy. Posttherapeutic imaging after 4 months did not show any evidence of tumor progression.

Surgical treatment of herniated lumbar intervertebral disks is a common procedure worldwide. However, recurrent herniated nucleus pulposus (re-HNP) may develop, complicating outcomes and patient management. The purpose of this study was to utilize machine-learning (ML) analytics to predict lumbar re-HNP, whereby a personalized risk prediction can be developed as a clinical tool. A retrospective, single center study was conducted of 2630 consecutive patients that underwent lumbar microdiscectomy (mean follow-up: 22-months). Various preoperative patient pain/disability/functional profiles, imaging parameters, and anthropomorphic/demographic metrics were noted. An Extreme Gradient Boost (XGBoost) classifier was implemented to develop a predictive model identifying patients at risk for re-HNP. The model was exported to a web application software for clinical utility. There were 1608 males and 1022 females, 114 of whom experienced re-HNP. Primary herniations were central (65.8%), paracentral (17.6%), and far lateral (17.1%). The XGBoost algorithm identified multiple re-HNP predictors and was incorporated into an open-access web application software, identifying patients at low or high risk for re-HNP. Preoperative VAS leg, disability, alignment parameters, elevated body mass index, symptom duration, and age were the strongest predictors. Our predictive modeling via an ML approach of our large-scale cohort is the first study, to our knowledge, that has identified significant risk factors for the development of re-HNP after initial lumbar decompression. We developed the re-herniation after decompression (RAD) profile index that has been translated into an online screening tool to identify low–high risk patients for re-HNP. Additional validation is needed for potential global implementation.

The aim of this study was to characterize the educational quality and reliability of YouTube videos related to low back pain (LBP) as well as to identify factors associated with the overall video quality. A review of YouTube was performed using two separate search strings. Video-specific characteristics were analyzed for the first 50 videos of each string. Seventy-seven eligible videos were identified as a result. The mean Journal of the American Medical Association score was 2.25 ± 1.09 (range: 0-4) out of 4. The mean Global Quality Score (GQS) score was 2.29 ± 1.37 (range: 1-4) out of 5. The mean LBP score (LPS) score was 3.83 ± 2.23 (range: 0-11) out of 15. Video power index was a predictor of GQS score (β = 55.78, p = 0.048), whereas the number of likes (β = -2.49, p = 0.047) and view ratio (β = -55.62, p = 0.049) were associated with lower quality scores. Days since initial upload (β = 0.32, p = 0.042) as well as like ratio (β = 0.37, p = 0.019) were independent predictors of higher LPS scores. The results of this study suggest that the overall reliability and educational quality of videos uploaded to YouTube concerning LBP are unsatisfactory. More popular videos demonstrated poorer educational quality than their less popular counterparts. As the prevalence of LBP rises, more accurate and thorough educational videos are necessary to ensure accurate information is available to patients.

OBJECTIVE: To assess the impact and procedural input of intraoperative ultrasound (IOUS) with contrast-enhanced ultrasound (CEUS) and ultrasound elastography on surgical decision making during the procedure and consequently the out-come after hepato-pancreatico-biliary (HPB) surgery. MATERIALS AND METHODS: Data of 50 consecutive patients, who underwent HPB surgery from 04/2018 to 07/2018 were prospectively collected for this study. During surgery, IOUS with a high-resolution ultrasound device using CEUS after bolus injection of 2.4–5 ml Sulphur hexafluoride microbubbles using a 6–9 MHz probe and a share wave and strain elastography was performed by an experienced examiner. Process and time analysis were carried out using mobile phone timer. RESULTS: The IOUS with CEUS and elastography correctly identified 42 malignant tumors and 4 benign lesions. In 3 cases, the examination provided false positive result (identifying 3 benign lesions as malignant) and in 1 case a malignant lesion was incorrectly assessed as benign (sensitivity 97,7%, specificity 57,1%, PPV 93,3% and NPV 80%). The specific question by the surgeon could be answered successfully in 98% of the cases. In 76% of the cases, there was a modification (42%) or a fundamental change (34%) of the planned surgical approach due to the information provided by the IOUS. Within the last group, the IOUS had a major impact on therapy outcome. In 7 patients an additional tumor resection was required, in 5 patients the tumor was assessed as inoperable, and in total in 5 patients an intraoperative RFA (4/5) or postoperative RITA (1/5) was required. Regarding procedural input, there was only a slight, but significant difference between the transport and set-up times before the intraoperative use (mean: 14 min 22 s) and the return transport (mean 13 min 6 s), (p = 0,038). The average examination time was 14 minutes, which makes only one third of the overall time demand. CONCLUSION: Combination of IOUS with CEUS and elastography in oncological HPB surgery provides valuable information that affects surgical decision-making. The procedural input of about 45 minutes seems to be a good investment considering the improvement of the surgical procedure and a significant modification of the therapy approach in the majority of the cases.

Background Vitamin K dependent coagulation factor deficiency type 1 (VKCFD1) is a rare hereditary bleeding disorder caused by mutations in γ-Glutamyl carboxylase (GGCX). VKCFD1 patients are treated life-long with high doses of vitamin K in order to correct the bleeding phenotype. However, normalization of clotting factor activities cannot be achieved for all VKCFD1 patients. Objective The current study aims to investigate the responsiveness to vitamin K for all reported GGCX mutations with respect to clotting factors in order to optimize treatment. Methods This study developed an assay using genetically engineered GGCX-/- cells, where GGCX mutations were analyzed with respect to their ability to γ-carboxylate vitamin K dependent pro-coagulatory and anti-coagulatory clotting factors by ELISA. Additionally, FVII activity was measured in order to proof protein functionality. For specific GGCX mutations immunofluorescent staining was performed to assess the intracellular localization of clotting factors with respect to GGCX wild-type and mutations. Results All GGCX mutations were categorized into responder and low responder mutations, thereby determining the efficiency of vitamin K supplementation. Most VKCFD1 patients have at least one vitamin K responsive GGCX allele that is able to γ-carboxylate clotting factors. In few patients, the hemorrhagic phenotype cannot be reversed by vitamin K administration because GGCX mutations on both alleles affect either structural or catalytically important sites thereby resulting into residual ability to γ-carboxylate clotting factors. Conclusion With these new functional data we can predict the hemorrhagic outcome of each VKCFD1 genotype thus recommending treatments with either vitamin K or Prothrombin Complex Concentrate.

Objective: To assess the degree, duration, mean absolute relative difference (MARD), and error analysis of discrepant values per continuous glucose monitoring (CGM) systems after hydroxyurea (HU) administration. Research Design and Methods: Inpatient glucometer and CGM data from 16 total pancreatectomy/islet autotransplantation patients using Dexcom Professional G4 and 12 patients using Dexcom G6 were analyzed after daily dosing with HU. Timing of HU dosing and median of 9.5 days of sensor and glucometer values were assessed per patient. Results: A large positive elevation of sensor readings was identified after HU dosing. The greatest discrepancy between glucometer and sensor readings occurred 0.5–2 h after HU administration [G4 (mean 3.0 mmol/L, median 2.4 mmol/L, MARD 55%), G6 (mean 4.2 mmol/L, median 4.6 mmol/L, MARD 91%)]. The discrepancy was

Eine 64-jahrige Patientin stellte sich mit Otalgie und Horminderung rechts vor. Otoskopisch zeigte sich rechts eine Vorwolbung mit Hypervaskularisation im anteroinferioren Trommelfellquadranten. Computertomographisch wurde eine osteolytische Lasion im Hypotympanon mit Befall der Felsenbeinspitze und des rechten parapharyngealen Raums sowie Ummauerung der A. carotis interna festgestellt. Bei der Magnetresonanztomographie verstarkte sich der Verdacht auf ein jugulotympanales Paragangliom. Das uber eine explorative Tympanotomie gewonnene Biopsiematerial wurde als polymorphes Low-Grade-Adenokarzinom begutachtet. Der Tumor wurde mittels definitiver Radiochemotherapie behandelt. In der Bildgebungsuntersuchung gab es 4 Monate nach Therapie keinen Anhalt fur einen Tumorprogress.

Background Duchenne muscular dystrophy is caused by mutations in the DMD gene, resulting in cardiomyopathy in all affected children by 18 years. Although cardiomyopathy is now the leading cause of mortality in these children, there is ongoing debate regarding timely diagnosis, secondary prevention, and treatment of this condition. The purpose of this study was to use exercise cardiac magnetic resonance imaging in asymptomatic young boys with Duchenne muscular dystrophy to describe their heart function and compare this with healthy controls. Methods We studied 11 boys with Duchenne muscular dystrophy aged 8.6 to 13.9 years and 11 healthy age- and sex-matched controls. Results Compared with the controls, boys with Duchenne muscular dystrophy had lower ejection fraction at rest (57% versus 63%; P = 0.004). During submaximal exercise, they reached similar peak tachycardia but increased their heart rate and cardiac output only half as much as controls (P = 0.003 and P = 0.014, respectively). End-systolic volume remained higher in boys with Duchenne muscular dystrophy both at rest and during exercise. When transthoracic echocardiography was compared with cardiac magnetic resonance imaging, 45% of the echocardiograms had suboptimal or poor views in the Duchenne muscular dystrophy group. Conclusions Boys with Duchenne muscular dystrophy had abnormalities in left ventricular systolic function that were exaggerated by exercise stress. Exercise cardiac magnetic resonance imaging is feasible in a select population of children with Duchenne muscular dystrophy, and it has the potential to unmask early signs of cardiomyopathy.

Given that a substantial proportion of the subgroup of COVID-19 patients that face a severe disease course are younger than 60 years, it is critical to understand the disease-specific characteristics of young COVID-19 patients. Risk factors for a severe disease course for young COVID-19 patients and possible non-linear influences remain unknown. Data were analyzed from COVID-19 patients with clinical outcome in a single hospital in Wuhan, China, collected retrospectively from Jan 24th to Mar 27th. Clinical, demographic, treatment and laboratory data were collected from patients' medical records. Uni- and multivariable analysis using logistic regression and random forest, with the latter allowing the study of non-linear influences, were performed to investigate the clinical characteristics of a severe disease course. A total of 762 young patients (median age 47 years, interquartile range [IQR] 38–55, range 18–60; 55.9% female) were included, as well as 714 elderly patients as a comparison group. Among the young patients, 362 (47.5%) had a severe/critical disease course and the mean age was statistically significantly higher in the severe subgroup than in the mild subgroup (59.3 vs. 56.0, Student's t-test: p p = 0.039) are particularly associated with the risk of developing severe COVID-19 specifically in young patients, whereas no such influence seems to exist for elderly patients. Additional analysis suggests that the influence of complement C3 in young patients is independent of age, gender, and comorbidities. Variable importance values and partial dependence plots obtained using random forests delivered additional insights, in particular indicating non-linear influences of risk factors on disease severity. This study identified increased levels of complement C3 as a unique risk factor for adverse outcomes specific to young COVID-19 patients.

Background Long-term course after atrial switch operation is determined by increasing right ventricular (RV) insufficiency. The aim of our study was to investigate subtle functional parameters by invasive measurements with conductance technique and noninvasive examinations with cardiac magnetic resonance imaging (CMR). Methods We used invasive (pressure–volume loops under baseline conditions and dobutamine) and noninvasive techniques (CMR with feature tracking [FT] method) to evaluate RV function. All patients had cardiopulmonary exercise testing (CPET). Results From 2011 to 2013, 16 patients aged 28.2 ± 7.3 (22–50) years after atrial switch surgery (87.5% Senning and 12.5% Mustard) were enrolled in this prospective study. All patients were in New York Heart Association (NYHA) class I to II and presented mean peak oxygen consumption of 30.1 ± 5.7 (22.7–45.5) mL/kg/min. CMR-derived end-diastolic volume was 110 ± 22 (78–156) mL/m2 and RV ejection fraction 41 ± 8% (25–52%). CMR-FT revealed lower global systolic longitudinal, radial, and circumferential strain for the systemic RV compared with the subpulmonary left ventricle. End-systolic elastance (Ees) was overall reduced (compared with data from the literature) and showed significant increase under dobutamine (0.80 ± 0.44 to 1.89 ± 0.72 mm Hg/mL, p ≤ 0.001), whereas end-diastolic elastance (Eed) was not significantly influenced (0.11 ± 0.70 to 0.13 ± 0.15 mm Hg/mL, p = 0.454). We found no relevant relationship between load-independent conductance indices and strain or CPET parameters. Conductance analysis revealed significant mechanical dyssynchrony, higher during diastole (mean 30 ± 4% baseline, 24 ± 6% dobutamine) than during systole (mean 17 ± 6% baseline, 19 ± 7% dobutamine). Conclusions Functional assessment of a deteriorating systemic RV remains demanding. Conductance indices as well as the CMR-derived strain parameters showed overall reduced values, but a significant relationship was not present (including CPET). Our conductance analysis revealed intraventricular and predominantly diastolic RV dyssynchrony.

NLRP1 was the first inflammasome-forming sensor to be identified, but only recently has its mode of action been in the spotlight. Two groups now report cryo-EM structures demonstrating how NLRP1 is kept in check by the dipeptidyl peptidase DPP9, and they illuminate how DPP9 inhibition leads to NLRP1 inflammasome activation.

The up-scaling of the pyrolysis technologies is the next step to achieve the industrial scale and to fulfill the energy and petrochemical demand in large-scale units. The overall goal of this study...

The onset of the economic crisis more than a decade ago posed extreme challenges to health care systems that may now be repeated with the COVID-19 pandemic The resulting policies produced a wide range of (in some cases, even opposite) outcomes: increased or decreased public expenditures for health care Curiously, however, countries that were considered particularly hard hit by the economic crisis showed different extremes of policy outcomes Investigating these developments requires a dynamic view and identifying explanations for government action in one direction or the other Using the lenses of several theoretical perspectives in public policy research, this article analyses the conditions under which public health expenditures changed in European Union member states after the financial crisis Why did certain countries, at first sight similarly affected, show opposite outcomes? A Qualitative Comparative Analysis (QCA) confirms that left-wing governments and coordinated market economies, in combination and alone, tended to increase public health expenditures in the short term, whereas countries where neither of these conditions was present decreased public health expenditures © The Author(s), 2021 Published by Cambridge University Press

BACKGROUND:Newborns, particularly premature newborns, are susceptible to hypothermia when transitioning from birth to admission to the NICU, potentially leading to increased mortality and morbidity. Despite attention to this issue, our rate of admission hypothermia was 39.8%.METHODS:We aimed to reduce the rate of admission hypothermia for all inborn infants admitted to our institution to RESULTS:We demonstrated a reduction in admission hypothermia from 39.8% to 9.9%, which was temporally related to educational efforts and expanded use of chemical heat mattresses and polyethylene bags. There was not an increase in admission hyperthermia over this time period. We found that our group at highest risk of admission hypothermia was not our most premature cohort but those infants born between 33 and 36 6/7 weeks’ gestation and those infants prenatally diagnosed with congenital anomalies.CONCLUSIONS:Expanded use of polyethylene bags and chemical heat mattresses can improve thermoregulation particularly when combined with staff education. Although premature infants have been the focus of many hypothermia prevention efforts, our data suggest that older infants, and those infants born with congenital anomalies, require additional attention.

OBJECTIVE: To investigate the diagnostic accuracy of high-resolution ultrasound (HRU) for the detection of hepatic metastases of breast cancer in a humanized tumour mouse (HTM) using clinical standard technology. In addition, the efficiency of standard contrast-enhanced ultrasound (CEUS) [microbubbles of sulphur hexafluoride] and CEUS using a novel VEGFR2-targeted contrast agent [BR55®] was examined. METHODS: A total of 14 HTM were sonographically examined twice. In addition to a human immune system, the animals developed hepatic tumour lesions after intrahepatic injection of BT-474 breast cancer cells. Digital cine loops from the arterial phase (15–35 sec), the portal venous phase (35–90 sec) and the late phase (3–15 min) of the entire liver were analysed. Data were correlated to histopathology. RESULTS: After 9 months, half of the mice (7/14) revealed the development of hepatic breast cancer metastases. The detection limit was 1 mm tumour diameter. In particular, the use of targeted contrast media reduced the needed tumour diameter and helped to precisely classify tumour tissue. In 93% (13/14), the findings of ultrasound could be approved by histological examination by the pathologist. CONCLUSIONS: This study in HTM demonstrated the high feasibility of tumour specific contrast media and standard HRU contrast agents to detect early liver metastases.

OBJECTIVES Venoarterial extracorporeal life support (ECLS) has emerged as a potentially life-saving treatment option in therapy-refractory cardiocirculatory failure, but longer-term outcome is poorly defined. Here, we present a comprehensive follow-up analysis covering all major organ systems. METHODS From February 2012 to December 2016, 180 patients were treated with ECLS for therapy-refractory cardiogenic shock or cardiac arrest. The 30-day survival was 43.9%, and 30-day survivors (n = 79) underwent follow-up analysis with the assessment of medium-term survival, quality of life, neuropsychological, cardiopulmonary and end-organ status. RESULTS After a median of 1.9 (1.1–3.6) years (182.4 patient years), 45 of the 79 patients (57.0%) were alive, 35.4% had died and 7.6% were lost to follow-up. Follow-up survival estimates were 78.0% at 1, 61.2% at 3 and 55.1% at 5 years. NYHA class at follow-up was ≤II for 83.3%. The median creatinine was 1.1 (1.0–1.4) mg/dl, and the median bilirubin was 0.8 (0.5–1.0) mg/dl. No patient required dialysis. Overall, 94.4% were free from moderate or severe disability, although 11.1% needed care. Full re-integration into social life was reported by 58.3%, and 39.4% were working. Quality of life was favourable for mental components, but a subset showed deficits in physical aspects. While age was the only peri-implantation parameter significantly predicting medium-term survival, adverse events and functional status at discharge or 30 days were strong predictors. CONCLUSIONS This study demonstrates positive medium-term outcome with high rates of independence in daily life and self-care but a subset of 10–20% suffered from sustained impairments. Our results indicate that peri-implantation parameters lack predictive power but downstream morbidity and functional status at discharge or 30 days can help identify patients at risk for poor recovery.

We present a new framework for sketch-based modeling and animation of 3D organic shapes that can work entirely in an intuitive 2D domain, enabling a playful, casual experience. Unlike previous sketch-based tools, our approach does not require a tedious part-based multi-view workflow with the explicit specification of an animation rig. Instead, we combine 3D inflation with a novel rigidity-preserving, layered deformation model, ARAP-L, to produce a smooth 3D mesh that is immediately ready for animation. Moreover, the resulting model can be animated from a single viewpoint --- and without the need to handle unwanted inter-penetrations, as required by previous approaches. We demonstrate the benefit of our approach on a variety of examples produced by inexperienced users as well as professional animators. For less experienced users, our single-view approach offers a simpler modeling and animating experience than working in a 3D environment, while for professionals, it offers a quick and casual workspace for ideation., ACM Transactions on Graphics, 39 (6), ISSN:0730-0301, ISSN:1557-7368

ObjectiveA high risk of morbidity and mortality is well documented in adults with a Fontan circulation. The difference in outcomes between those with and without significant morbidity at the time of transition to adult care has not been well characterised.MethodsWe analysed clinical outcomes in patients enrolled in the Australian and New Zealand Fontan Registry ≥16 years of age. Low risk (LR) Fontan patients were defined as those without history of sustained arrhythmia, thromboembolic event, transplantation, Fontan conversion, protein-losing enteropathy, plastic bronchitis, New York Heart Association class III/IV and/or moderate/severe atrioventricular valve regurgitation or ventricular dysfunction. Increased risk (IR) patients had one or more risk factor.ResultsInclusion criteria were met in 822 patients; mean age 26±8 years, median follow-up from age 16 was 9 years, 203 had atriopulmonary connection (APC) and 619 had total cavopulmonary connection (TCPC). Survival at 30 years was higher in the LR versus IR; 94% versus 82% (p=0.005), 89% versus 77% (p=0.07) for APC and 96% versus 89% (p=0.05) for TCPC. LR patients experienced less Fontan failure (HR 0.34, 95% CI 0.23 to 0.49, pConclusionsClinical outcomes for adolescents LR at transition to adult care are markedly superior to those who have established risk factors for Fontan failure, which is an important consideration when formulating individualised long-term risk estimates and counselling patients.

Background The influence of adrenaline during cardiopulmonary resuscitation (CPR) on the neurological outcome of cardiac arrest survivors is unclear. As little is known about the pathophysiological effects of adrenaline on cerebral oxygen delivery and cerebral metabolism we investigated its effects on parameters of cerebral oxygenation and cerebral metabolism in a pig model of CPR. Methods Fourteen pigs were anesthetized, intubated and instrumented. After 5 min of cardiac arrest CPR was started and continued for 15 min. Animals were randomized to receive bolus injections of either 15 or 30 μg/kg adrenaline every 5 min after commencement of CPR. Results Measurements included mean arterial pressure (MAP), intracranial pressure (ICP), cerebral perfusion pressure (CPP), cerebral regional oxygen saturation (rSO2), brain tissue oxygen tension (PbtO2), arterial and cerebral venous blood gases and cerebral microdialysis parameters, e.g. lactate/pyruvate ratio. Adrenaline induced a significant increase in MAP and CPP in all pigs. However, increases in MAP and CPP were short-lasting and tended to decrease with repetitive bolus administration. There was no statistical difference in any parameter of cerebral oxygenation or metabolism between study groups. Conclusions Both adrenaline doses resulted in short-lasting CPP peaks which did not translate into improved cerebral tissue oxygen tension and metabolism. Further studies are needed to determine whether other dosing regimens targeting a sustained increase in CPP, may lead to improved brain oxygenation and metabolism, thereby improving neurological outcome of cardiac arrest patients.

Objectives To evaluate intraoperative contrast‐enhanced ultrasound (IoCEUS) and intraoperative shear wave elastography (IoSWE) for characterization of focal pancreatic lesions (FPLs) in correlation with postoperative histologic results. Thereby, the impact of intraoperative ultrasound (US) on pancreas surgery was evaluated. Methods Intraoperative CEUS and SWE data from 54 patients, who underwent pancreas surgery between 2017 and 2019, were analyzed retrospectively. Ultrasound examinations were performed with multifrequency linear/T‐shaped transducers (3–9 MHz) on a high‐end US device (LOGIQ E9; GE Healthcare, Chicago, IL). To analyze FPL stiffness by SWE, regions of interest were placed to measure the shear wave speed (meters per second) and stiffness (kilopascals). After intravenous bolus injections of 2.4 to 10 mL of sulfur hexafluoride microbubbles, a dynamic analysis of FPL microvascularization from arterial to late phases was performed using IoCEUS considering hypoenhancement/irregular vascularization of macrocystic/small solid FPL malignancy criteria. Ultrasound findings were correlated with postoperative histologic results. The impact of intraoperative US on surgery was documented in each case. Results Of 54 FPLs, IoCEUS could correctly characterize 39 of 39 malignant and 6 of 15 benign FPLs; IoSWE 29 of 39 as malignant and 7 of 15 as benign. Intraoperative CEUS's sensitivity was 100%; specificity, 40%; accuracy, 83.3%; positive predictive value, 81.3%; and negative predictive value, 100% (P

Purpose: We aimed to compare treatment results in and outside of a randomized trial and to confirm factors influencing outcome in a large retrospective cohort of nonmetastatic medulloblastoma treated in Austria, Switzerland and Germany. Methods and Materials: Patients with nonmetastatic medulloblastoma (n = 382) aged 4 to 21 years and primary neurosurgical resection between 2001 and 2011 were assessed. Between 2001 and 2006, 176 of these patients (46.1%) were included in the randomized HIT SIOP PNET 4 trial. From 2001 to 2011 an additional 206 patients were registered to the HIT 2000 study center and underwent the identical central review program. Three different radiation therapy protocols were applied. Genetically defined tumor entity (former molecular subgroup) was available for 157 patients. Results: Median follow-up time was 7.3 (range, 0.09-13.86) years. There was no difference between HIT SIOP PNET 4 trial patients and observational patients outside the randomized trial, with 7 years progression-free survival rates (PFS) of 79.5% ± 3.1% versus 78.7% ± 3.1% (P= .62). On univariate analysis, the time interval between surgery and irradiation (≤ 48 days vs ≥ 49 days) showed a strong trend to affect PFS (80.4% ± 2.2% vs 64.6% ± 9.1%;P= .052). Furthermore, histologically and genetically defined tumor entities and the extent of postoperative residual tumor influenced PFS. On multivariate analyses, a genetically defined tumor entity wingless-related integration site-activated vs non-wingless-related integration site/non-SHH, group 3 hazard ratio, 5.49;P= .014) and time interval between surgery and irradiation (hazard ratio, 2.2;P= .018) were confirmed as independent risk factors. Conclusions: Using a centralized review program and risk-stratified therapy for all patients registered to the study center, outcome was identical for patients with nonmetastatic medulloblastoma treated on and off the randomized HIT SIOP PNET 4 trial. The prognostic values of prolonged time to RT and genetically defined tumor entity were confirmed.

OBJECTIVES: The aim of the study was to determine whether patients with eosinophilic esophagitis (EoE) have lower bone mineral density (BMD) than expected and if bone deficits are more pronounced in subgroups of patients according to comorbidities (atopic disease and joint hypermobility) or treatments (dietary restriction, medication exposure). STUDY DESIGN: Retrospective chart review was performed to obtain clinical data, including length of diagnosis, comorbidities, and methods of treatment for patients with EoE ages 3 to 21 years who had a lumbar spine dual-energy x-ray absorptiometry scan performed between 2014 and 2017. BMD was standardized by calculation of age, sex, and race-specific z scores. RESULTS: A total of 269 patients met study criteria. The mean BMD z score (−0.55, 95% confidence interval: −0.68, −0.42) was lower than expected (P

Osteoporosis is a major concern in patients with Duchenne muscular dystrophy. In this novel study of teriparatide treatment in 6 patients with severe osteoporosis, bone health (fractures, vertebral morphometry, and DXA) remained stable, with no adverse events. These findings will help inform future osteoporosis research in this challenging population. Despite standard therapy with vitamin D and bisphosphonates (BP), many patients with Duchenne muscular dystrophy (DMD) continue to sustain fragility fractures due to long-term glucocorticoid treatment and limited mobility. We aimed to evaluate the safety and efficacy of teriparatide for the treatment of severe osteoporosis in adolescent and young adult patients with DMD. We prospectively treated 6 patients with DMD who had severe osteoporosis with teriparatide 20 mcg subcutaneously daily for 1–2 years. Inclusion criteria were long-term glucocorticoid therapy, and severe osteoporosis despite treatment with BP, or intolerance to BP. We examined long bone and vertebral fracture outcomes, including vertebral morphometry measures, bone mineral density and content, bone formation markers, safety indices, and adverse events. The mean age at teriparatide start was 17.9 years (range 13.9–22.1 years). All 6 patients were on daily glucocorticoids (mean ± SD; duration 10.9 ± 2.5 years) and 5 were non-ambulatory. Five patients had been treated with BP for 7.9 ± 4.2 years. All had vertebral and a history of long bone fragility fractures at baseline. Vertebral heights and Genant fracture grading remained stable. Long bone fracture rate appeared to decrease (from 0.84/year to 0.09/year); one patient sustained a long bone fracture at 6 months of treatment. Trajectories for change in bone mineral density and content were not different post- vs. pre-teriparatide. Procollagen type 1 amino-terminal propeptide (P1NP) increased, while laboratory safety indices remained stable and non-concerning. No adverse events were observed. In six patients with DMD treated with teriparatide for severe osteoporosis, we observed stable bone health and modest increases in P1NP, without safety concerns. Further studies are needed to better understand teriparatide efficacy for treatment of osteoporosis in patients with DMD.

Purpose Assessment of the cochlear implant (CI) electrode array position using flat-detector computed tomography (FDCT) to test dependence of postoperative outcome on intracochlear electrode position. Methods A total of 102 patients implanted with 107 CIs underwent FDCT. Electrode position was rated as 1) scala tympani, 2) scala vestibuli, 3) scalar dislocation and 4) no deconvolution. Two independent neuroradiologists rated all image data sets twice and the scalar position was verified by a third neuroradiologist. Presurgical and postsurgical speech audiometry by the Freiburg monosyllabic test was used to evaluate auditory outcome after 6 months of speech rehabilitation. Results Electrode array position was assessed by FDCT in 107 CIs. Of the electrodes 60 were detected in the scala tympani, 21 in the scala vestibuli, 24 electrode arrays showed scalar dislocation and 2 electrodes were not placed in an intracochlear position. There was no significant difference in rehabilitation outcomes between scala tympani and scala vestibuli inserted patients. Rehabilitation was also possible in patients with dislocated electrodes. Conclusion The use of FDCT is a reliable diagnostic method to determine the position of the electrode array. In our study cohort, the electrode position had no significant impact on postoperative outcome except for non-deconvoluted electrode arrays.

Background Nephropathy is a known complication of the Fontan circulation, but its determinants have not been identified and patient outcomes are also still unknown. Methods The Australia and New Zealand Fontan Registry was used to identify those who underwent Fontan operation before and survived beyond 16-years-old with an intact Fontan circulation. Serum creatinine values were collected for each patient between 16 and 25 years and at recent follow-up. The Modification of Diet in Renal Disease (MDRD) equation was used to calculate eGFR. Patient outcomes were obtained from the Registry. Fontan failure was defined as death, transplantation, plastic bronchitis, protein losing enteropathy, Fontan takedown and NYHA class III-IV. Results Serum creatinine measurements were available for 328 patients. Renal dysfunction was defined as eGFR Conclusion By the time they reach adulthood, 20% of patients with a Fontan circulation have renal dysfunction by eGFR calculation. Over the course of one decade, Fontan-associated nephropathy appears well tolerated.