Dosimetric benefit of online treatment plan adaptation in stereotactic ultrahypofractionated MR-guided radiotherapy for localized prostate cancer.

Background: Apart from superior soft tissue contrast, MR-guided stereotactic body radiation therapy (SBRT) offers the chance for daily online plan adaptation. This study reports on the comparison of dose parameters before and after online plan adaptation in MR-guided SBRT of localized prostate cancer. Materials and methods: 32 consecutive patients treated with ultrahypofractionated SBRT for localized prostate cancer within the prospective SMILE trial underwent a planning process for MR-guided radiotherapy with 37.5 Gy applied in 5 fractions. A base plan, derived from MRI simulation at an MRIdian Linac, was registered to daily MRI scans (predicted plan). Following target and OAR recontouring, the plan was reoptimized based on the daily anatomy (adapted plan). CTV and PTV coverage and doses at OAR were compared between predicted and adapted plans using linear mixed regression models. Results: In 152 out of 160 fractions (95%), an adapted radiation plan was delivered. Mean CTV and PTV coverage increased by 1.4% and 4.5% after adaptation. 18% vs. 95% of the plans had a PTV coverage ≥95% before and after online adaptation, respectively. 78% vs. 100% of the plans had a CTV coverage ≥98% before and after online adaptation, respectively. The D0.2cc for both bladder and rectum were <38.5 Gy in 93% vs. 100% before and after online adaptation. The constraint at the urethra with a dose of <37.5 Gy was achieved in 59% vs. 93% before and after online adaptation. Conclusion: Online adaptive plan adaptation improves target volume coverage and reduces doses to OAR in MR-guided SBRT of localized prostate cancer. Online plan adaptation could potentially further reduce acute and long-term side effects and improve local failure rates in MR-guided SBRT of localized prostate cancer.

EFFects of Exposure and Cognitive behavioral Therapy for chronic BACK pain ("EFFECT-BACK"): study protocol for a randomized controlled trial.

INTRODUCTION: Chronic back pain is a widespread medical condition associated with high socioeconomic costs and increasing prevalence. Despite the advanced implementation of multidisciplinary approaches, providing a satisfactory treatment offer for those affected is often not possible. Exposure therapy (EXP) promises to be an effective and economical form of treatment and in a previous pilot study showed to be superior to cognitive behavioral therapy (CBT) in reducing perceived limitations of movement. The current study aims to further compare the efficacy of both treatment methods and identify those patient groups that particularly benefit from EXP. METHODS: The general objective of this randomized multicenter clinical trial (targeted N = 380) is to improve and expand the range of treatments available to patients with chronic back pain. As the primary objective of the study, two different psychological treatments (EXP and CBT) will be compared. The primary outcome measure is a clinically significant improvement in pain-related impairment, measured by the QPBDS, from baseline to 6-month follow-up. Secondary outcome measures are absolute changes and clinically significant improvements in variables coping, psychological flexibility, depressiveness, catastrophizing, exercise avoidance and fear of exercise, and intensity of pain. Participants are recruited in five psychological and medical centers in Germany and receive ten sessions of manualized therapy by trained licensed CBT therapists or clinical psychologists, who are currently in their post-gradual CBT training. Potential predictors of each treatment's efficacy will be explored with a focus on avoidance and coping behavior. CONCLUSION: This study will be the first RCT to compare CBT and EXP in chronic back pain in a large sample, including patients from different care structures due to psychological and medical recruitment centers. By identifying and exploring potential predictors of symptom improvement in each treatment group, this study will contribute to enable a more individualized assignment to treatment modalities and thus improves the care situation for chronic back pain and helps to create a customized treatment program for subgroups of pain patients. If our findings confirm EXP to be an efficacious and efficient treatment concept, it should gain more attention and be further disseminated. TRIAL REGISTRATION: ClinicalTrials.gov NCT05294081. Registered on 02 March 2022.

Randomized phase III GnG study on two schedules of gemtuzumab ozogamicin as adjunct to intensive induction therapy and double-blinded intensive post-remission therapy with or without glasdegib in patients with newly diagnosed acute myeloid leukemia.

Not available.

Long-term trends in hepatitis C prevalence, treatment uptake and liver-related events in the Swiss HIV Cohort Study.

BACKGROUND AND AIMS: Treatment for chronic hepatitis C virus (HCV) infections changed dramatically in the last decade. We assessed changes in the prevalence of replicating HCV infection, treatment uptake and liver-related morbidity and mortality in persons with HIV (PWH) and hepatitis C in the Swiss HIV cohort study. METHODS: We included all cohort participants between 2002 and 2021. We assessed yearly prevalence of replicating HCV infection, overall and liver-related mortality, as well as the yearly incidence of liver-related events in persons with at least one documented positive HCV-RNA. RESULTS: Of 14 652 participants under follow-up, 2294 had at least one positive HCV-RNA measurement. Of those, 1316 (57%) ever received an HCV treatment. Treatment uptake increased from 8.1% in 2002 to a maximum of 32.6% in 2016. Overall, prevalence of replicating HCV infection declined from 16.5% in 2004 to 1.3% in 2021. HCV prevalence declined from 63.2% to 7.1% in persons who inject drugs, and from 4.1% to 0.6% in men who have sex with men. Among the 2294 persons with replicating HCV infection, overall mortality declined from a maximum of 3.3 per 100 patient-years (PY) to 1.1 per 100 PY, and incidence of liver-related events decreased from 1.4/100 PY to 0.2/100 PY. CONCLUSIONS: The introduction of DAA therapy was associated with a more than 10-fold reduction in prevalence of replicating HCV infection in PWH, approaching the estimates in the general population. Overall mortality and liver-related events declined substantially in persons living with HIV and hepatitis C.

Prevalence and influencing factors for artifact development in breast MRI-derived maximum intensity projections.

BACKGROUND: Magnetic resonance imaging (MRI) provides high diagnostic sensitivity for breast cancer. However, MRI artifacts may impede the diagnostic assessment. This is particularly important when evaluating maximum intensity projections (MIPs), such as in abbreviated MRI (AB-MRI) protocols, because high image quality is desired as a result of fewer sequences being available to compensate for problems. PURPOSE: To describe the prevalence of artifacts on dynamic contrast enhanced (DCE) MRI-derived MIPs and to investigate potentially associated attributes. MATERIAL AND METHODS: For this institutional review board approved retrospective analysis, MIPs were generated from subtraction series and cropped to represent the left and right breasts as regions of interest. These images were labeled by three independent raters regarding the presence of MRI artifacts. MRI artifact prevalence and associations with patient characteristics and technical attributes were analyzed using descriptive statistics and generalized linear models (GLMMs). RESULTS: The study included 2524 examinations from 1794 patients (median age 50 years), performed on 1.5 and 3.0 Tesla MRI systems. Overall inter-rater agreement was kappa = 0.54. Prevalence of significant unilateral artifacts was 29.2% (736/2524), whereas bilateral artifacts were present in 37.8% (953/2524) of all examinations. According to the GLMM, artifacts were significantly positive associated with age (odds ratio [OR] = 1.52) and magnetic field strength (OR = 1.55), whereas a negative effect could be shown for body mass index (OR = 0.95). CONCLUSION: MRI artifacts on DCE subtraction MIPs of the breast, as used in AB-MRI, are a relevant topic. Our results show that, besides the magnetic field strength, further associated attributes are patient age and body mass index, which can provide possible targets for artifact reduction.

Protocol of a randomised controlled phase II clinical trial investigating PREoperative endoscopic injection of BOTulinum toxin into the sphincter of Oddi to reduce bile leakage after hepatic resection: the PREBOT-II trial.

INTRODUCTION: Bile leakage represents a major cause of morbidity following hepatic resection. Although most patients can be managed non-operatively, this complication requires diagnostics and therapeutic interventions. Preoperative endoscopic injection of botulinum toxin (BTX) into the sphincter of Oddi represents an innovative approach to prevent bile leakage. The aim of the PREBOT-II trial is to generate the first randomised controlled trial data on the safety, feasibility and efficacy of preoperative endoscopic BTX injection into the sphincter of Oddi to prevent bile leakage following hepatic resection. METHODS AND ANALYSIS: The PREBOT-II trial is an investigator-initiated, exploratory, multicentre, randomised, controlled, open-label, phase II clinical trial with two parallel study groups. 70 patients scheduled for hepatic resection will be randomised to either the intervention or the control group. Patients of the intervention group will undergo preoperative endoscopic injection of BTX into the sphincter of Oddi 3-10 days before surgery, whereas in the control group only hepatic resection will be performed. The primary endpoint is the occurrence of a postoperative bile leakage within 30 days after hepatic resection according to the definition of the International Study Group of Liver Surgery. The secondary endpoints comprise further postoperative morbidity parameters such as severity of postoperative bile leakage, post-hepatectomy haemorrhage or liver failure, mortality and quality of life up to 3 months after hepatic resection. Safety and feasibility of the procedure will also be recorded. ETHICS, FUNDING AND DISSEMINATION: The PREBOT-II trial has been approved by the German Federal Institute for Drugs and Medical Devices (reference number 4044932) and the Ethics Committee of Heidelberg University (reference number AFmu-558/2021). This trial is supported by the German Federal Ministry of Education and Research. The results will be presented at national and international conferences and published in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: DRKS00024061, EudraCT: 2020-006001-35.

Involving, Empowering, and Training End Users with Disabilities to Fully Participate in the Web Accessibility Directive Objectives First Results from the UPowerWAD Project.

In this paper, we present the first results from the UPowerWAD Project - a project which aims to raise awareness and to empower and train people with disabilities to take active participation in the implementation of the Web Accessibility Directive (WAD). We give an overview of the results on how to capture and categorize feedback from users in the context of web accessibility and present best practices for structuring and reporting web accessibility issues. The results will be discussed focusing on the relevance and implications for further steps in the project.

MELD-Na Alterations on the Liver Transplant Waiting List and Their Impact on Listing Outcome.

BACKGROUND: Dynamic MELD deterioration (Delta MELD) during waiting time was shown to have significant impact on post-transplant survival. The aim of this study was to analyze the impact of MELD-Na score alterations on waiting list outcomes in liver transplant candidates. METHOD: 36,806 patients listed at UNOS for liver transplantation in 2011-2015 were analyzed according to their delisting reasons. Several different MELD-Na alterations during waiting time were analyzed (e.g., maximal change, last change before delisting/transplantation). Outcome estimates were calculated according to MELD-Na scores at listing and Delta MELD. RESULTS: Patients who died while on the waiting list showed a significantly higher deterioration in MELD-Na during the waiting time (6.8 ± 8.4 points) than stable patients who remained actively listed (-0.1 ± 5.2 points; p < 0.01). Patients who were considered too healthy for transplantation improved by more than 3 points on average during the waiting time. The mean peak MELD-Na alteration during the waiting time was 10.0 ± 7.6 for patients who died on the waiting list, compared to 6.6 ± 6.1 in the group of patients who finally underwent transplantation. CONCLUSIONS: Deterioration of MELD-Na during waiting time and maximal MELD-Na deterioration have a significant negative impact on the liver transplant waiting list outcome.

Vascular impulse technology versus elevation for reducing the swelling of upper and lower extremity joint fractures.

Soft-tissue conditioning due to posttraumatic oedema after complicated joint fractures is a central therapeutic aspect both pre- and postoperatively. On average, 6-10 days pass until the patient is suitable for surgery. This study compares the decongestant effect of vascular impulse technology (VIT) with that of conventional elevation. In this monocentric RCT, 68 patients with joint fractures of the upper (n = 36) and lower (n = 32) extremity were included and randomized after consent in a 1:1 ratio. Variables were evaluated for all fractures together and additionally subdivided into upper or lower extremity for better clinical comparability. Primary endpoint was the time in days from hospital admission to operability. Secondary endpoints were total length of stay, oedema reduction, pain intensity, complications, and revisions. The time from admission until operability was reduced by 1.4 (95% CI - 0.4; 3.1) days in the mITT analysis (p = 0.120) and was statistically significant with 1.7 (95% CI 0.1; 3.3) days in the as-treated sensitivity analysis (pAT = 0.038). Significantly less pain and a faster oedema reduction were found in the intervention group. Due to rare occurrences, nothing can be concluded regarding complications and revisions. Administration of VIT therapy did not lead to a significant reduction in time until operability in the whole population but was superior to elevation for soft-tissue conditioning and pain reduction. However, there was a significant reduction by 2.5 days (95% CI 0.7; 4.3) in the subgroup of lower extremity fractures. VIT therapy therefore seems to be a helpful tool in the treatment of posttraumatic oedema after complex joint fractures of the lower and upper extremity, especially in tibial head and lower leg fractures.

Anti-SARS-CoV-2 antibody-containing plasma improves outcome in patients with hematologic or solid cancer and severe COVID-19: a randomized clinical trial.

Patients with cancer are at high risk of severe coronavirus disease 2019 (COVID-19), with high morbidity and mortality. Furthermore, impaired humoral response renders severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines less effective and treatment options are scarce. Randomized trials using convalescent plasma are missing for high-risk patients. Here, we performed a randomized, open-label, multicenter trial ( https://www.clinicaltrialsregister.eu/ctr-search/trial/2020-001632-10/DE ) in hospitalized patients with severe COVID-19 (n = 134) within four risk groups ((1) cancer (n = 56); (2) immunosuppression (n = 16); (3) laboratory-based risk factors (n = 36); and (4) advanced age (n = 26)) randomized to standard of care (control arm) or standard of care plus convalescent/vaccinated anti-SARS-CoV-2 plasma (plasma arm). No serious adverse events were observed related to the plasma treatment. Clinical improvement as the primary outcome was assessed using a seven-point ordinal scale. Secondary outcomes were time to discharge and overall survival. For the four groups combined, those receiving plasma did not improve clinically compared with those in the control arm (hazard ratio (HR) = 1.29; P = 0.205). However, patients with cancer experienced a shortened median time to improvement (HR = 2.50; P = 0.003) and superior survival with plasma treatment versus the control arm (HR = 0.28; P = 0.042). Neutralizing antibody activity increased in the plasma cohort but not in the control cohort of patients with cancer (P = 0.001). Taken together, convalescent/vaccinated plasma may improve COVID-19 outcomes in patients with cancer who are unable to intrinsically generate an adequate immune response.

Long-term follow-up MRI shows no hastening of adjacent segment degeneration following cervical disc arthroplasty.

Cervical disc arthroplasty is an established procedure, but studies with data on long-term clinical outcome, reoperation for symptomatic adjacent segment degeneration (sASD), and degenerative changes based on MRI findings are rare. Thus, a file review was performed and patients with complete documentation of neurological status at preoperative, postoperative, 12 month, 3-4 years follow-up including surgical reports for reoperation with a minimum follow-up of 9 years were included. Final follow-up assessment included a physical examination, assessment of pain levels, Odoms criteria, Neck disability index. The degeneration of each cervical segment at preoperative and at final follow-up was assessed using an MRI. Forty-six out of 68 included patients participated, the mean follow-up was 11 (range 9-15) years, at which 71.7% of patients were free of arm pain, 52.2% of patients were free of neck pain, 63% of patients had no sensory dysfunction, and full motor strength was noted in 95.6% of patients. The clinical success rate was 76.1%, the mean NDI was 12%. Overall repeated procedure rate was 17%, the reoperation rate for sASD was 9%, and removal of CDA was performed in 4%. MRI showed progressive degeneration but no significant changes of SDI from preoperative to final follow-up.

Timing of reconstruction of the lower urinary tract in pediatric kidney transplant recipients: A CERTAIN multicenter analysis of current practice.

BACKGROUND: Preexistent LUTD are considered a hostile environment, which might negatively impact KTx survival. In such cases, surgical reconstruction of the bladder is required. However, there is still disagreement on the optimal timing of the reconstruction procedure. METHODS: This is a multicenter analysis of data from the CERTAIN Registry. Included were 62 children aged 8.18 ± 4.90 years, with LUTD. Study endpoints were the duration of initial posttransplant hospitalization, febrile UTIs, and a composite failure endpoint comprising decline of eGFR, graft loss, or death up to 5 years posttransplant. Outcome was compared to matched controls without bladder dysfunction. RESULTS: Forty-one patients (66.1%) underwent pretransplant and 14 patients (22.6%) posttransplant reconstruction. Bladder augmentation was performed more frequently in the pretransplant (61%) than in the posttransplant group (21%, p = .013). Outcome in the pre- and posttransplant groups and in the subgroups of patients on pretransplant PD with major bladder surgery either pre- (n = 14) or posttransplant (n = 7) was comparable. Outcomes of the main study cohort and the matched control cohort (n = 119) were comparable during the first 4 years posttransplant; at year 5, there were more events of transplant dysfunction in the study cohort with LUTD than in controls (p = .03). CONCLUSIONS: This multicenter analysis of the current practice of LUTD reconstruction in pediatric KTx recipients shows that pre- or posttransplant surgical reconstruction of the lower urinary tract is associated with a comparable 5-year outcome.

Monotonicity conditions for avoiding counterintuitive decisions in basket trials.

In a basket trial, a new treatment is tested in different subgroups, called the baskets. In oncology, the baskets usually comprise patients with different primary tumor sites but a common biomarker. Most basket trials are uncontrolled phase II trials and investigate a binary endpoint such as tumor response. To combine the data of baskets that show a similar response to the treatment, many basket trial designs use Bayesian borrowing methods. This increases the power compared to a basketwise analysis. However, it can lead to posterior probabilities that are not monotonically increasing in the number of responses. We show that, as a consequence, two types of counterintuitive decisions can arise-one that occurs within a single trial and one that occurs when the results are compared between different trials. We propose two monotonicity conditions for the inference in basket trials. Using a design recently proposed by Fujikawa and colleagues, we investigate the case of a single-stage basket trial with equal sample sizes in all baskets and show that, as the number of baskets increases, these conditions are violated for a wide range of different borrowing strengths. We show that in the investigated scenarios pruning baskets can help to ensure that the monotonicity conditions hold and investigate how this affects type I error rate and power.

Potential of blood-based biomarker approaches in endometrium and breast cancer: a case-control comparison study.

PURPOSE: Endometrial carcinoma is the second most common gynecological malignancy. Until today lacking a screening tool. A blood-based biomarker could help address this need. METHODS: The expression levels of 30 acylcarnitines, 18 amino acids, 6 miRNAs, and 7 DNA methylation sites were measured in blood samples from 331 women (20 EC, 14 benign uterine lesions (benign), 140 breast cancers (BC), 157 controls). Areas under the ROC curves (AUC), sensitivity (sens.) and specificity (spec.) were computed to identify the variables best distinguishing. RESULTS: The best top ten markers for the four comparisons (cancer vs. cancer-free; EC vs. BC, EC vs. controls; EC vs. benign), were identified via AUC. Malonylcarnitine distinguished best patients with EC from controls (AUC: 0.827, sens. 80%, spec. 73.1%) or BC (AUC: 0.819, sens. 84.3%, spec. 80%) being most notable. Tryptophan best differentiated benign from EC (AUC: 0.846, sens. 70%, spec. 92.9%). CONCLUSIONS: The levels of the analyzed blood markers yielded promising results in the detection of EC and warrant further evaluation.

Publication rate and research topics of studies in pediatric kidney transplantation.

BACKGROUND: The quality of medical care for pediatric kidney transplant recipients depends on sound evidence from published clinical trials. METHODS: We examined the publication rate, time to publication, and factors associated with publication of studies in pediatric kidney transplantation registered on ClinicalTrials.gov from 1999 to 2020. RESULTS: We identified 136 studies with an overall enrollment of 36255 study participants, of which only 58.8% have been published yet. Unpublished studies included data from 14 350 participants. The median time to publication was 25 months (range, 0-117) with a significantly shorter time to publication in more recent years. The most frequently investigated research topic was immunosuppressants (49.3%), followed by perioperative management (11.0%) and infectiology (10.3%). The percentage of published studies was highest for the topic steroid withdrawal (87.5%), followed by infectiology (78.6%), and nutrition, sports and quality of life (71.4%). Studies, which were co-funded by industry, showed a significantly higher 5-year publication rate (p = 0.019). CONCLUSIONS: In conclusion, nearly half of all studies in pediatric kidney transplantation remain unpublished. Non-publication of studies might lead to a publication bias with a negative impact on clinical decision-making.

Pregnancy with inflammatory bowel disease: Outcomes for mothers and their children at a European tertiary care center.

AIM: The study aimed at investigating pregnancy complications, birth outcomes, and postnatal child development in pregnancies of women with inflammatory bowel diseases (IBDs). METHODS: This is an uncontrolled retrospective single-center study between 2014 and 2019. It is a mixed-method cross-sectional study using data from (1) electronic patient records and (2) questionnaires and copies of mothers' and children's health booklets. Disease activity and IBD medications were analyzed and related to pregnancy complications, birth outcomes, and postnatal child development using mixed models for statistical analyses. RESULTS: Fifty live births from 46 patients were included. Disease activity anytime during pregnancy occurred in 56%. Biologics were applied in ca. 25% of pregnancies, mostly only through the second trimester. Pregnancies of mothers with active disease were slightly shorter than those of mothers with inactive disease (37.4 weeks vs. 38.9 weeks). Adverse pregnancy outcomes were reported in 28% of the live births, including small for gestational age in 6%, low birth weight in 18%, and preterm birth in 20%. Postnatal developmental abnormalities and health problems were reported in 26.8% of the children. Mixed model analyses failed to reveal significant associations between IBD activity and IBD medications during pregnancy and pregnancy complications, perinatal birth outcomes, and postnatal child development. CONCLUSION: Despite a tendency of shorter pregnancies in patients with active IBD and lower birth weight and birth size in patients with IBD-related therapy during pregnancy, disease activity and medications did not significantly influence pregnancy, birth, and developmental outcomes.

Estimands-A Basic Element for Clinical Trials.

BACKGROUND: Clinical trials are of central importance for the evaluation and comparison of treatments. The transparency and intelligibility of the treatment effect under investigation is an essential matter for physicians, patients, and health-care authorities. The estimand framework has been introduced because many trials are deficient in this respect. METHODS: Introduction, definition, and application of the estimand framework on the basis of an example and a selective review of the literature. RESULTS: The estimand framework provides a systematic approach to the definition of the treatment effect under investigation in a clinical trial. An estimand consists of five attributes: treatment, population, variable, population-level summary, and handling of intercurrent events. Each of these attributes is defined in an interdisciplinary discussion during the trial planning phase, based on the clinical question being asked. Special attention is given to the handling of intercurrent events (ICEs): these are events-e.g., discontinuation or modification of treatment or the use of emergency medication-that can occur once the treatment has begun and might affect the possibility of observing the endpoints or their interpretability. There are various strategies for the handling of ICEs; these can, for example, also reflect the existing intention-to-treat (ITT) principle. Per-protocol analyses, in contrast, are prone to bias and cannot be represented in a sensible manner by an estimand, although they may be performed as a supplementary analysis. The discussion of potential intercurrent events and how they should appropriately be handled in view of the aim of the trial must already take place in the planning phase. CONCLUSION: Use of the estimand framework should make it easier for both physicians and patients to understand what trials reveal about the efficacy of treatment, and to compare the results of different trials.

Rationale and design of the 2 by 2 factorial design GnG-trial: a randomized phase-III study to compare two schedules of gemtuzumab ozogamicin as adjunct to intensive induction therapy and to compare double-blinded intensive postremission therapy with or without glasdegib in older patients with newly diagnosed AML.

BACKGROUND: Overall survival remains poor in older patients with acute myeloid leukemia (AML) with less than 10% being alive after 5 years. In recent studies, a significant improvement in event-free, relapse-free and overall survival was shown by adding gemtuzumab ozogamicin (GO), a humanized antibody-drug conjugate directed against CD33, to intensive induction therapy once or in a sequential dosing schedule. Glasdegib, the small-molecule inhibitor of smoothened (SMO), also showed improved overall survival in patients not eligible for intensive chemotherapy when combined with low-dose cytarabine compared to low-dose cytarabine alone. These findings warrant further investigations in the phase III GnG trial. METHODS/DESIGN: This is a randomized phase III trial with measurable residual disease (MRD) after induction therapy and event-free survival (EFS) as primary endpoints. The two research questions are addressed in a 2 by 2 factorial design. Patients age 60 years and older are upfront randomized 1:1 in one of the two induction arms: GO administered to intensive induction therapy on days 1,4, and 7 versus GO administered once on day 1 (GO-147 versus GO-1), and double-blinded 1:1 in one of the subsequent treatment arms glasdegib vs. placebo as adjunct to consolidation therapy and as single-agent maintenance therapy for six months. Chemotherapy backbone for induction therapy consists of standard 7 + 3 schedule with cytarabine 200 mg/m2 continuously days 1 to 7, daunorubicin 60 mg/m2 days 1, 2, and 3 and high-dose cytarabine (1 g/m2, bi-daily, days 1, 2, and 3) for consolidation therapy. Addressing two primary endpoints, MRD-negativity after induction therapy and event-free survival (EFS), 252 evaluable patients are needed to reject each of the two null hypotheses at a two-sided significance level of 2.5% with a power of at least 85%. ETHICS AND DISSEMINATION: Ethical approval and approvals from the local and federal competent authorities were granted. Trial results will be reported via peer-reviewed journals and presented at conferences and scientific meetings. TRIAL STATUS: Protocol version: 1st version 20.10.2020, no amendments yet. Study initiation on February 16, 2021. First patient was recruited on April 1st. TRIAL REGISTRATION: ClinicalTrials.gov NCT04093505 ; EudraCT 2019-003913-32. Registered on October 30, 2018.

Role of fecal calprotection in predicting endoscopic recurrence in postoperative Crohn's disease.

BACKGROUND AND AIMS: Fecal calprotectin (fCP) has been shown to correlate with endoscopic disease activity in Crohn's disease (CD). The aim of this study was to evaluate its role in predicting early endoscopic recurrence in postoperative CD. METHODS: Patients who underwent CD-related intestinal resection with ileocolonic anastomosis were prospectively followed up until ileocolonoscopy was performed around 12 months post-surgery. Endoscopic recurrence (ER) was defined as modified Rutgeerts score i2b or higher. Endoscopic still images were reviewed by 2 independent reviewers blinded to fCP results. Stool specimens were collected 6 months post-surgery and a multivariate logistic regression model was established to explore the predictive value of fCP for ER. RESULTS: 79 patients were included. FCP was significantly associated with endoscopic recurrence (p = .036). A cut-off value of fCP of 267 µg/g at 6 months post-surgery predicted ER with a sensitivity of 61.8% and a specificity of 72.7% (AUC 0.669). A prediction model subsuming age at diagnosis and fCP 6 months post-surgery were significantly associated with ER (fCP at 6 months [p = .007] and age at diagnosis [p = .004], multivariate analysis). CONCLUSIONS: FCP 6 months after surgery and age at diagnosis predict early ER at 1 year postoperatively. However, the low sensitivity of fCP still suggests the necessity of endoscopy as a gold standard for the assessment of postoperative recurrence of CD.KEY SUMMARYWhat is already known? Fecal calprotectin (fCP) correlates with endoscopic disease activity. Endoscopic recurrence occurs in up to 70% of patients after intestinal resection within 1 year.What are the significant and/or new findings of this study? Fecal calprotectin 6 months post-surgery and age at diagnosis significantly predict endoscopic recurrence at 1 year. Due to low sensitivity fCP cannot replace the necessity of endoscopy for accurate assessment of postoperative recurrence.

Outbreaks of publications about emerging infectious diseases: the case of SARS-CoV-2 and Zika virus.

BACKGROUND: Outbreaks of infectious diseases generate outbreaks of scientific evidence. In 2016 epidemics of Zika virus emerged, and in 2020, a novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused a pandemic of coronavirus disease 2019 (COVID-19). We compared patterns of scientific publications for the two infections to analyse the evolution of the evidence. METHODS: We annotated publications on Zika virus and SARS-CoV-2 that we collected using living evidence databases according to study design. We used descriptive statistics to categorise and compare study designs over time. RESULTS: We found 2286 publications about Zika virus in 2016 and 21,990 about SARS-CoV-2 up to 24 May 2020, of which we analysed a random sample of 5294 (24%). For both infections, there were more epidemiological than laboratory science studies. Amongst epidemiological studies for both infections, case reports, case series and cross-sectional studies emerged first, cohort and case-control studies were published later. Trials were the last to emerge. The number of preprints was much higher for SARS-CoV-2 than for Zika virus. CONCLUSIONS: Similarities in the overall pattern of publications might be generalizable, whereas differences are compatible with differences in the characteristics of a disease. Understanding how evidence accumulates during disease outbreaks helps us understand which types of public health questions we can answer and when.