Minced Autologous Chondral Fragments with Fibrin Glue as a Simple Promising One-Step Cartilage Repair Procedure: A Clinical and MRI Study at 12-Month Follow-Up.

OBJECTIVE: The aim of this study was to investigate early radiological and clinical outcome of autologous minced cartilage treatment as a single-step treatment option in patients with a chondral or osteochondral lesion (OCL) in the knee. DESIGN: Eighteen patients with an OCL in the knee were included. Cartilage from healthy-appearing loose bodies and/or the periphery of the defect were minced into small chips and sealed in the defect using fibrin glue. Preoperatively, and at 3 (n = 14) and 12 (n = 18) months follow-up, magnetic resonance imaging (MRI) was performed. The Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART) 2.0 score was used to assess the cartilage repair tissue on MRI at 12 months. The International Knee Documentation Score, Knee Injury and Osteoarthritis Outcome Score, EuroQoL-5D, and Visual Analogue Scale pain were collected preoperatively and 12 months after surgery. RESULTS: Three months postoperative, MRI showed complete defect filling in 11 out of 14 patients. Mean MOCART 2.0 score at 12 months was 65.0 ± 18.9 with higher scores for lateral femoral chondral lesions compared to medial femoral chondral lesions (75.8 ± 14.3, 52.5 ± 15.8 respectively, P = 0.02). Clinical and statistical significant improvements were observed in the patient-reported outcome measures at 12 months postoperatively compared to preoperatively. CONCLUSION: Treatment of OCLs using the autologous minced cartilage procedure resulted in good cartilage repair measured by MOCART 2.0. Clinically relevant improvements were observed in the clinical scores. This study suggests autologous minced cartilage as a promising, single-step treatment for OCLs.

Endometriosis and irritable bowel syndrome: similarities and differences in the spectrum of comorbidities.

STUDY QUESTION: Do the spectrum and prevalence of comorbidities of endometriosis and irritable bowel syndrome (IBS) overlap? SUMMARY ANSWER: Despite several overlapping symptoms, the most significantly associated comorbidities of endometriosis and IBS are different and are rather related to the organ systems primarily involved in the index diagnosis. WHAT IS KNOWN ALREADY: Endometriosis and IBS both have several similar unspecific symptoms, such as recurrent abdominal pain, cramping and anxiety, and both diseases affect young women and are associated with a number of comorbidities causing a poor quality of life. However, a detailed study, revealing the full spectrum of endometriosis and IBS comorbidities in the same study population, is lacking. STUDY DESIGN, SIZE, DURATION: This article presents a retrospective in silico analysis of the data from a large nationwide biobank-based cohort consisting of 121 773 women. After excluding all first- and second-degree relatives, the data of up to 65 421 women were analyzed. PARTICIPANTS/MATERIALS, SETTING, METHODS: International Classification of Disease-10 diagnosis main codes associated with endometriosis (N80) and IBS (K58) diagnoses were identified from the Estonian Biobank dataset by linking with the Estonian Health Insurance Fund and other relevant registries. The associations between N80 and K58 and other diagnosis codes were tested using logistic regression, adjusting for age at recruitment and 10 genetic principal components to account for potential population stratification. Bonferroni correction was applied to account for multiple testing. MAIN RESULTS AND THE ROLE OF CHANCE: Both women with endometriosis and IBS suffered from more conditions compared to the control group, with 226 and 428 diagnosis codes statistically significantly more frequent in women with respective diagnosis compared to controls. Women suffering from both conditions had 275 significantly associated comorbidities. A remarkable proportion of women with IBS or endometriosis suffered also from endometriosis (9.0%) or IBS (13.6%), respectively. In endometriosis, the most prevalent diagnoses were related to diseases of the genitourinary system (33 N-category codes) and in women with IBS, the most associated diagnoses were related to digestive disorders and gastrointestinal tract (52 codes from K-category). Among the most significant diagnoses in endometriosis were uterine leiomyomas (D25), menstrual disorders (N92) and infertility (N97) (P < 1 × 10-315 for all), and in IBS, lactose intolerance (E73), gastritis and duodenitis (K29) and functional dyspepsia (K30) were in the top list of most significant comorbidities (P < 1 × 10-315 for all). LIMITATIONS, REASONS FOR CAUTION: The information about the severity stages of endometriosis and subtypes of IBS was not available for analysis. The findings may not be fully extrapolated to all female populations, because all participants were from one geographic area and had good access to health services. WIDER IMPLICATIONS OF THE FINDINGS: These findings support previous studies that have found a high prevalence of pre-selected comorbidities in women with endometriosis and IBS. However, taking into account the differences in the full spectrum of comorbidities of endometriosis and IBS may aid in diagnosing these disorders. Women and healthcare providers need to be aware that women with endometriosis are at high risks of complications during pregnancy and should be carefully monitored. STUDY FUNDING/COMPETING INTEREST(S): This research was funded by the Estonian Research Council (grant PRG1076), Horizon 2020 innovation grant (ERIN, grant no. EU952516), Enterprise Estonia (grant no. EU48695), MSCA-RISE-2020 project TRENDO (grant no. 101008193) and by the European Union through the European Regional Development Fund (Projects no. 2014-2020.4.01.15-0012 and no. 2014-2020.4.01.16-0125). The authors have no conflicts of interest to declare. TRIAL REGISTRATION NUMBER: N/A.

[Liver metastases of neuroendocrine tumors]. / Lebermetastasen neuroendokriner Tumoren.

Neuroendocrine liver metastases (NELM) are very heterogeneous with respect to the clinical presentation and the prognosis. The treatment of NELMs requires a multidisciplinary approach and patients with NELM should be referred to a specialized center. When possible, the resection of NELMs provides the best long-term results. The general selection criteria for liver resection include an acceptable general physical condition for a large liver operation, tumors with a favorable differentiation grade 1 or 2, a lack of extrahepatic lesions, a sufficient residual liver volume and the possibility to resect at least 70% of the metastases. Supplementary treatment, including simultaneous liver ablation, are generally safe and can increase the number of patients who can be considered for surgery. For patients with resectable NELM, the resection of the primary tumor is recommended either in a 2-stage or combined procedure. In selected patients with nonresectable NELM a liver transplantation can be carried out, which can be associated with excellent long-term results.

7-Tesla MRI Evaluation of the Knee, 25 Years after Cartilage Repair Surgery: The Influence of Intralesional Osteophytes on Biochemical Quality of Cartilage.

OBJECTIVE: To evaluate the morphological and biochemical quality of cartilage transplants and surrounding articular cartilage of patients 25 years after perichondrium transplantation (PT) and autologous chondrocyte transplantation (ACT) as measured by ultra-high-field 7-Tesla (7T) magnetic resonance imaging (MRI) and to present these findings next to clinical outcome. DESIGN: Seven PT patients and 5 ACT patients who underwent surgery on the femoral condyle between 1986 and 1996 were included. Patient-reported outcome measures (PROMs) were assessed by the clinical questionnaires: Knee injury and Osteoarthritis Outcome Score (KOOS), International Knee Documentation Committee (IKDC), and Visual Analogue Scale (VAS) for knee pain. The morphological (MOCART score) and biochemical quality (glycosaminoglycans [GAGs] content and collagen integrity) of cartilage transplants and surrounding articular cartilage were analyzed by 7T MRI. The results of the PT and ACT patients were compared. Finally, a detailed morphological analysis of the grafts alone was performed. RESULTS: No statistically significant difference was found for the PROMs and MOCART scores of PT and ACT patients. Evaluation of the graft alone showed poor repair tissue quality and high prevalence of intralesional osteophyte formation in both the PT and ACT patients. Penetration of the graft surface by the intralesional osteophyte was related to biochemically damaged opposing tibial cartilage; GAG content was significantly lower in patients with an osteophyte penetrating the graft surface. CONCLUSIONS: Both PT and ACT patients have a high incidence of intralesional osteophyte formation 25 years after surgery. The resulting biochemical damage to the opposing tibial cartilage might be dependent on osteophyte morphology.

MR compatibility, safety and accuracy of the redesigned UMC Utrecht single needle implant device.

Purpose. The Utrecht single needle implant device (SNID) was redesigned to increase needle insertion velocity. The purpose of this study is to evaluate the magnetic resonance compatibility, safety and accuracy of the implant device preparing its application in a patient study to investigate the feasibility of inserting a brachytherapy needle into the prostate to a defined tumor target point.Methods. Several experiments were performed to evaluate the mechanical and radiofrequency safety of the needle system, the magnetic field perturbation, the calibration of the implant device in the MR coordinate system, functioning of the implant device during imaging and accuracy of needle insertion.Results. Endurance experiments showed the mechanical safety of the needle system. Magnetic field perturbation was acceptable with induced image distortions smaller than 0.5 mm for clinical MR sequences. Calibration of the implant device in the MR coordinate system was reproducible with average error (mean±standard deviation) of 0.2 ± 0.4 mm, 0.1 ± 0.3 mm and 0.6 ± 0.6 mm in thex,y- andz- direction, respectively. The RF safety measurement showed for clinical MR imaging sequences maximum temperature rises of 0.2 °C at the entry and tip points of the needle. Simultaneous functioning of the implant device and imaging is possible albeit with some intensity band artifacts in the fast field echo images. Finally, phantom measurements showed deviations amounting 2.5-3.6 mm measured as target-to-needle distance at a depth of 12 cm.Conclusions. This preclinical evaluation showed that the MR compatibility, safety and accuracy of the redesigned UMC Utrecht SNID allow its application in a patient study on the feasibility of inserting a brachytherapy needle into the prostate to a defined tumor target point.

The effect of anti-TNF treatment on body composition and insulin resistance in patients with rheumatoid arthritis.

Given the link between systemic inflammation, body composition and insulin resistance (IR), anti-inflammatory therapy may improve IR and body composition in inflammatory joint diseases. This study assesses the IR and beta cell function in rheumatoid arthritis (RA) patients with active disease compared to osteoarthritis (OA) patients and investigates the effect of anti-TNF treatment on IR, beta cell function and body composition in RA. 28 Consecutive RA patients starting anti-TNF treatment (adalimumab), and 28 age, and sex-matched patients with OA were followed for 6 months. Exclusion criteria were use of statins, corticosteroids, and cardiovascular or endocrine co-morbidity. Pancreatic beta cell function and IR, using the homeostasis model assessment (HOMA2), and body composition, using dual-energy X-ray absorptiometry (DXA) were measured at baseline and 6 months. At baseline, IR [1.5 (1.1-1.8) vs. 0.7 (0.6-0.9), 100/%S] and beta cell function (133% vs. 102%) were significantly (p < 0.05) higher in RA patients with active disease as compared to OA patients. After 6 months of anti-TNF treatment, IR [1.5 (1.1-1.8) to 1.4 (1.1-1.7), p = 0.17] slightly improved and beta cell function [133% (115-151) to 118% (109-130), p <0.05] significantly improved. Improvement in IR and beta cell function was most pronounced in RA patients with highest decrease in CRP and ESR. Our observations indicate that IR and increased beta cell function are more common in RA patients with active disease. Anti-TNF reduced IR and beta cell function especially in RA patients with highest decrease in systemic inflammation and this effect was not explained by changes in body composition.

A randomized controlled TRIal of cognitive BEhavioral therapy for high Catastrophizing in patients undergoing lumbar fusion surgery: the TRIBECA study.

BACKGROUND: Around 20% of patients undergoing spinal fusion surgery have persistent back or leg pain despite surgery. Pain catastrophizing is the strongest psychological predictor for chronic postsurgical pain. Psychological variables are modifiable and could be target for intervention. However, randomized controlled trials evaluating the effectiveness of psychological interventions to reduce chronic pain and disability after spinal fusion in a population of patients with high preoperative pain catastrophizing scores are missing. The aim of our study is to examine whether an intervention targeting pain catastrophizing mitigates the risk of chronic postsurgical pain and disability. Our primary hypothesis is that targeted perioperative cognitive behavioral therapy decreases the risk of chronic postsurgical pain and disability after spinal fusion surgery in high catastrophizing patients. METHODS: We will perform a two-center prospective, single-blind, randomized, controlled study comparing lumbar spinal fusion surgery outcome between 2 cohorts. Adult patients selected for lumbar spinal fusion with decompression surgery and a minimum score of 24 on the pain catastrophizing scale will be randomized with 1:1 allocation for either perioperative cognitive behavioral therapy (intervention group) or a perioperative education plus progressive exercise program (control group). Patients randomized to the intervention group will receive six individual sessions of cognitive behavioral therapy, two sessions before the operation and four after. Primary outcome is the Core Outcome Measures Index at 12 months. Secondary outcomes include pain, disability, depression and quality of life. DISCUSSION: This is the first trial that evaluates the effectiveness of cognitive behavioral therapy as a perioperative tool to improve pain and disability after spinal fusion surgery in comparison with an educational/exercise control intervention, in patients with high levels of pain catastrophizing. If perioperative cognitive behavioral therapy proves to be effective, this might have important clinical implications, reducing the incidence of chronic postsurgical pain and improving outcome after spinal fusion surgery. TRIAL REGISTRATION: Clinicaltrials ( NCT03969602 ). Registered 31 May 2019.

Intraprostatic Cancer Recurrence following Radical Radiotherapy on Transperineal Template Mapping Biopsy: Implications for Focal Ablative Salvage Therapy.

PURPOSE: Men in whom external beam radiotherapy fails are usually placed on delayed hormone therapy. Some of these men have localized recurrence that might be suitable for further local therapy. We describe patterns of recurrence and suitability for focal ablative therapy in those undergoing transperineal template prostate mapping biopsies. MATERIALS AND METHODS: The study included 145 consecutive patients (December 2007 to May 2014) referred with suspicion of recurrence due to rising prostate specific antigen after external beam radiotherapy or brachytherapy who underwent transperineal template prostate mapping biopsies. Suitability for focal ablative therapy required the cancer to be unifocal or unilateral, or bilateral/multifocal with 1 dominant index lesion and secondary lesions with Gleason score 3+3=6 with no more than 3 mm cancer core involvement. RESULTS: Mean patient age was 70.7 (SD 5.8) years. Median prostate specific antigen at time of transperineal template prostate mapping biopsy was 4.5 ng/ml (IQR 2.5-7.7). Overall 75.9% (110) were suitable for a form of focal salvage treatment, 40.7% (59) were suitable for quadrant ablation, 14.5% (21) hemiablation, 14.5% (21) bilateral focal ablation and 6.2% (9) for index lesion ablation. CONCLUSIONS: Three-quarters of patients who have localized radiorecurrent prostate cancer may be suitable for focal ablative therapy to the prostate based on transperineal template prostate mapping biopsies.

Central nervous signs, blindness and cerebral vermicosis in free-ranging peregrine falcons (Falco peregrinus) associated with aberrant larval migrations.

Four free-ranging peregrine falcons (Falco peregrinus) were submitted with a history of unilateral or bilateral blindness and central nervous signs to a veterinary clinic in Germany. There were no indications of trauma or ocular disease. Likewise, other differential diagnoses for CNS signs were ruled out within the diagnostic process. The clinical diagnostic panel in live falcons included general examination, radiography, endoscopy, hematology, ophthalmoscopy and parasitological examination of the feces, blood gas analysis and blood chemistry as well as computed tomography, and magnetic resonance imaging (MRI). A complete pathological and histopathological examination was performed post-mortem. The only common finding in all birds was an infection with the nematode parasite Serratospiculum tendo. The parasite was confirmed morphologically and via PCR. In two falcons intracerebral vermicoses was suspected in MRI and confirmed in subsequent histopathology, but molecular biological identification of the parasite species failed from brain tissue. Until today, S. tendo had been reported to affect the respiratory system, the liver and different parts of the gastrointestinal tract and to cause cachexia, inappetence, regurgitation, dyspnea and general signs of illness such as lethargy, poor plumage, and reduced reproduction. Our findings indicate that aberrant migration should be considered as cause for CNS signs in falcons. As S. tendo might be a possible cause for this, CNS signs might be included in the list of clinical signs of serratospiculiasis in falcons.

Cognitive behavioral therapy or graded exercise therapy compared with usual care for severe fatigue in patients with advanced cancer during treatment: a randomized controlled trial.

BACKGROUND: Cancer-related fatigue remains a prevalent and burdensome symptom experienced by patients with advanced cancer. Our aim was to assess the effects of cognitive behavioral therapy (CBT) or graded exercise therapy (GET) on fatigue in patients with advanced cancer during treatment with palliative intent. PATIENTS AND METHODS: A randomized controlled trial was conducted from 1 January 2013 to 1 September 2017. Adult patients with locally advanced or metastatic cancer who reported severe fatigue during treatment [Checklist Individual Strength, subscale fatigue severity (CIS-fatigue) ≥35] were accrued across nine centers in The Netherlands. Patients were randomly assigned to either 12 weeks of CBT or GET, or usual care (1 : 1: 1, computer-generated sequence). Primary outcome was CIS-fatigue at 14 weeks. Secondary outcomes included fatigue measured with the European Organisation for Research and Treatment of Cancer-Quality of Life Questionnaire (EORTC-QLQ-C30), quality of life, emotional functioning, physical functioning, and functional impairments at baseline, 14, 18, and 26 weeks. RESULTS: Among 134 participants randomized, the mean age was 63 (standard deviation 9) years and 77 (57%) were women. Common diagnoses included: breast (41%), colorectal (28%), and prostate cancer (17%). A total of 126 participants completed assessment at 14 weeks. Compared with usual care, CBT significantly reduced fatigue [difference -7.2, 97.5% confidence interval (CI) -12.7 to -1.7; P = 0.003, d = 0.7], whereas GET did not (-4.7, 97.5% CI -10.2 to 0.9; P = 0.057, d = 0.4). CBT significantly reduced EORTC-QLQ-C30 fatigue (-13.1, 95% CI -22.1 to -4.0; P = 0.005) and improved quality of life (10.2, 95% CI 2.4 to 17.9; P = 0.011) and physical functioning (7.1, 95% CI 0.5 to 13.7; P = 0.036) compared with usual care. Improvement in emotional functioning and decrease in functional impairments failed to reach significance. GET did not improve secondary outcomes compared with usual care. CONCLUSIONS: Among advanced cancer patients with severe fatigue during treatment, a CBT intervention was more effective than usual care for reducing fatigue. Following GET, patients reported lower fatigue, but results were not significant, probably due to a smaller sample size and lower adherence than anticipated. TRIAL REGISTRATION: Netherlands National Trial Register, identifier: NTR3812.

Rituximab in routine care of severe active rheumatoid arthritis : A prospective, non-interventional study in Germany.

OBJECTIVE: To assess safety, effectiveness and onset of effect of rituximab (RTX) in routine clinical treatment of severe, active rheumatoid arthritis (RA). METHODS: Prospective, multi-centre, non-interventional study in rheumatological outpatient clinics or private practices in Germany. RTX-naïve adult patients were to receive RTX according to marketing authorisation and at their physician's discretion. Also according to their physician's discretion, patients could receive a second cycle of RTX (re-treatment = treatment continuation). Major outcome was the change in Disease Activity Score based on 28-joints count and erythrocyte sedimentation rate (DAS28-ESR) over 24 weeks and during 6 months of re-treatment. RESULTS: Overall, 1653 patients received at least one cycle RTX; 99.2% of these had received disease-modifying antirheumatic drugs (DMARD) pre-treatment and 75.5% anti-tumor necrosis factor(TNF)­α pre-treatment. After a mean interval of 8.0 months, 820 patients received RTX re-treatment. Mean DAS28-ESR decreased from 5.3 at baseline to 3.8 after 24 weeks (-1.5 [95% confidence interval, CI: -1.6; -1.4]), and from 4.1 at start of cycle 2 to 3.5 at study end (change from baseline: -1.8 [95% CI: -2.0; -1.7]). Improvements in DAS28-ESR and Health Assessment Questionnaire (HAQ) score occurred mainly during the first 12 weeks of RTX treatment, with further DAS28-ESR improvement until week 24 or month 6 of re-treatment. Improvements in DAS28-ESR and EULAR responses were more pronounced in seropositive patients. RF was a predictor of DAS28-ESR change to study end. Safety analysis showed the established profile of RTX. CONCLUSION: RTX was safe and effective in a real-life setting with rapid and sustained improvement in RA signs and symptoms.

Treating benign ureteroenteric strictures: 27-year experience comparing endourological techniques with open surgical approach.

PURPOSE: To compare open surgical anastomotic revision with endourological techniques for the treatment of ureteroenteric strictures in patients with urinary diversions. METHODS: All records of patients treated for ureteroenteric strictures in our clinic between 1989 and 2016 were retrospectively reviewed. In 76 patients, 161 completed procedures were analyzed: 26 open revisions vs. 135 endourological treatments, including balloon dilation, Wallstent and/or laser vaporization. RESULTS: Median follow-up was 34 months. At 60 months, patency rates were 69% (95% CI 52-92%) after open vs. 27% (95% CI 19-39%) after endo-treatment (p = 0.003); median patency duration was 15.5 vs. 5 months, respectively (p = 0.014). Eventually, 15% of patients required open surgery after primary endo-treatment and 21% received endoscopic re-treatment after primary open surgery. Cox regression analysis revealed no confounding factors among the risk factors added to the model. Complication rates were higher after open surgery (27% Clavien 2, 12% Clavien 3-4 vs. 5% Clavien 1-2, 3% Clavien 3, p = 0.528). Median postoperative hospital stay was 14 days (open) vs. 2 days (endo), p < 0.001. Mean estimated glomerular filtration rate improved with + 17 (open) vs. + 8.1 (endo), p = 0.024. Renal function was compromised in 8% of patients in the open surgery group vs. 6% in the endo-treatment group. CONCLUSIONS: In these patients, in terms of patency and patency duration, open surgery was superior to endourology. Nevertheless, endourological treatments offer a safe and less-invasive alternative to delay or avoid open surgery, especially in patients who are unfit for open surgery.

The effects of golimumab treatment on systolic and diastolic left ventricular function in ankylosing spondylitis.

BACKGROUND: Diastolic left ventricular (LV) dysfunction appears more prevalent in ankylosing spondylitis (AS). The effects of tumor necrosis factor alpha (TNF-α) blocking therapy, a strong and effective anti-inflammatory drug, on diastolic LV function in AS are unknown. The objective of the study was to find the effects of 1-year treatment with golimumab 50 mg subcutaneously once per month on systolic and diastolic LV dysfunction in AS patients. METHODS: Forty consecutive AS patients were treated with TNF-α blocking therapy for 1 year. Transthoracic echocardiography was performed in all patients at baseline and after 1 year of treatment. RESULTS: Diastolic LV function improved after treatment in four out of six (67%) AS patients who completed follow-up (P=0.125), and did not develop or worsen in any of the other patients. Treatment with TNF-α blocking therapy had no effect on systolic LV function. CONCLUSION: These findings give support to the hypothesis that diastolic LV dysfunction improves during treatment with TNF-α blocking therapy.

Association of Target Therapy Gene Expression with Metastasizing of Clear-Cell Renal Cell Carcinoma.

We analyzed association of the levels of VEGFA, RAF1, and mTOR gene expression in the tissue of clear-cell renal cell carcinoma (ccRCC) with tumor metastasizing. Significant association with metastases was found only for VEGFA gene: OR=6.641, 95%CI=2.111-20.696. The risk of metastasis associated with reduced expression of VEGFA gene - 2.467, 95%CI=1.238-4.915. An association of VEGFA gene expression with the time to the metastasis appearance was revealed (p=0.0005). Reduced expression of the VEGFA gene is associated with reduction of the time to metastasis appearance; the median of this time is shifted from 46 to 2 months. Analysis of tumor samples with reduced expression of the VEGFA gene revealed association of increased expression of RAF1 (p=0.003) and mTOR genes (p=0.038) with metastasis.

Expression Profiles of Genes-Potential Therapy Targets-and Their Relationship to Survival in Renal Cell Carcinoma.

The main mechanisms of pathogenesis of clear cell renal cell carcinoma (CCRCC) are realized through the PI3K-AKT-mTOR and Ras-RAF-ERK signaling pathways. Targeted therapy is directed primarily at the genes and their encoded products that are components of these pathways. The levels of expression and coexpression of target genes were determined, and the difference in the functioning of the genes of one of the two major signaling pathways in tumors of CCRCC patients with different life duration (more and less than 3.5 years) and the relationship of the VEGFA gene expression level with the life duration was revealed.

Cardiac-Specific Conversion Factors to Estimate Radiation Effective Dose From Dose-Length Product in Computed Tomography.

OBJECTIVES: This study sought to determine updated conversion factors (k-factors) that would enable accurate estimation of radiation effective dose (ED) for coronary computed tomography angiography (CTA) and calcium scoring performed on 12 contemporary scanner models and current clinical cardiac protocols and to compare these methods to the standard chest k-factor of 0.014 mSv·mGy-1cm-1. BACKGROUND: Accurate estimation of ED from cardiac CT scans is essential to meaningfully compare the benefits and risks of different cardiac imaging strategies and optimize test and protocol selection. Presently, ED from cardiac CT is generally estimated by multiplying a scanner-reported parameter, the dose-length product, by a k-factor which was determined for noncardiac chest CT, using single-slice scanners and a superseded definition of ED. METHODS: Metal-oxide-semiconductor field-effect transistor radiation detectors were positioned in organs of anthropomorphic phantoms, which were scanned using all cardiac protocols, 120 clinical protocols in total, on 12 CT scanners representing the spectrum of scanners from 5 manufacturers (GE, Hitachi, Philips, Siemens, Toshiba). Organ doses were determined for each protocol, and ED was calculated as defined in International Commission on Radiological Protection Publication 103. Effective doses and scanner-reported dose-length products were used to determine k-factors for each scanner model and protocol. RESULTS: k-Factors averaged 0.026 mSv·mGy-1cm-1 (95% confidence interval: 0.0258 to 0.0266) and ranged between 0.020 and 0.035 mSv·mGy-1cm-1. The standard chest k-factor underestimates ED by an average of 46%, ranging from 30% to 60%, depending on scanner, mode, and tube potential. Factors were higher for prospective axial versus retrospective helical scan modes, calcium scoring versus coronary CTA, and higher (100 to 120 kV) versus lower (80 kV) tube potential and varied among scanner models (range of average k-factors: 0.0229 to 0.0277 mSv·mGy-1cm-1). CONCLUSIONS: Cardiac k-factors for all scanners and protocols are considerably higher than the k-factor currently used to estimate ED of cardiac CT studies, suggesting that radiation doses from cardiac CT have been significantly and systematically underestimated. Using cardiac-specific factors can more accurately inform the benefit-risk calculus of cardiac-imaging strategies.

Intensity of factor VIII treatment and the development of inhibitors in non-severe hemophilia A patients: results of the INSIGHT case-control study.

Essentials Research suggests that intensive treatment episodes may increase the risk to develop inhibitors. We performed an international nested case-control study with 298 non-severe hemophilia A patients. Surgery and a high dose of factor VIII concentrate were associated with increased inhibitor risk. Physicians need to review arguments for factor VIII dose and elective surgery extra critically. SUMMARY: Background Inhibitor development is a major complication of treatment with factor VIII concentrates in hemophilia. Findings from studies among severe hemophilia A patients suggest that intensive treatment episodes increase the risk of developing inhibitors. Objectives We set out to assess whether intensive treatment is also associated with an increased risk of inhibitor development among non-severe hemophilia A patients. Patients/Methods We performed a nested case-control study. A total of 75 inhibitor patients (cases) and 223 control patients were selected from 2709 non-severe hemophilia A patients (FVIII:C, 2-40%) of the INSIGHT cohort study. Cases and controls were matched for date of birth and cumulative number of exposure days (EDs) to FVIII concentrates. Conditional logistic regression was used to calculate both unadjusted and adjusted odds ratios (aOR); the latter were adjusted for a priori specified confounders. Results Peak treatment of 5 or 10 consecutive EDs did not increase inhibitor risk (aOR, 1.0; 95% confidence interval (CI), 0.4-2.5; and aOR, 1.8; CI, 0.6-5.5, respectively). Both surgical intervention (aOR, 4.2; CI, 1.7-10.3) and a high mean dose (> 45 IU kg-1 /ED) of FVIII concentrate (aOR, 7.5; CI, 1.6-35.6) were associated with an increased inhibitor risk. Conclusions Our findings suggest that high-dose FVIII treatment and surgery increase the risk of inhibitor development in non-severe hemophilia A. Together with the notion that non-severe hemophilia A patients are at a lifelong risk of inhibitor development, we suggest that in the future physicians will review the arguments for the FVIII dose and elective surgery extra critically.

Adaptive cone-beam CT planning improves long-term biochemical disease-free survival for 125I prostate brachytherapy.

PURPOSE: Determining the independent effect of additional intraoperative adaptive C-arm cone-beam CT (CBCT) planning vs. transrectal ultrasound (TRUS)-guided interactive planning alone in 125I brachytherapy for prostate cancer (PCa) on biochemical disease-free survival (BDFS). METHODS AND MATERIALS: T1/T2-stage PCa patients receiving TRUS-guided brachytherapy from 2000 to 2014 were analyzed. From October 2006, patients received additional intraoperative adaptive CBCT planning for dosimetric evaluation and subsequent remedial seed placement in underdosed areas. Patients were stratified according to the National Comprehensive Cancer Network (NCCN) risk classification. Kaplan-Meier analysis was used to estimate BDFS (primary outcome), overall survival, and PCa-specific survival (secondary outcomes). Cox regression was used to assess the relation between CBCT use and biochemical failure (BF) and overall mortality. RESULTS: In all, 1623 patients were included. Median followup was 99 months (interquartile range 70-115) for TRUS patients (n = 613) and 51 months (interquartile range 29-70) for CBCT patients (n = 1010). BF occurred 203 times and 206 patients died, 26 from PCa. For TRUS and CBCT patients, 7-year BDFS was 87.2% vs. 93.5% (log rank: p = 0.04) for low, 75.9% vs. 88.5% (p < 0.001) for intermediate, and 57.1% vs. 85.0% for high-risk patients (p < 0.001). For TRUS and CBCT patients, 7-year PCa-specific survival was 96.0% vs. 100% (p < 0.0001). After Cox regression, CBCT patients had lower hazard of BF: hazard ratio (HR) 0.25 (95% confidence interval [CI]: 0.18-0.33; p < 0.0001). Corrected for confounders, CBCT remained a predictor of BF: HR 0.51 (95% CI: 0.31-0.86; p = 0.01) but not for overall mortality: HR 0.66 (95% CI: 0.40-1.07; p = 0.09). CONCLUSIONS: Additional intraoperative adaptive CBCT planning in 125I prostate brachytherapy leads to a significant increase in BDFS in all NCCN risk groups.

Transplacental transmission of Neospora caninum in moose (Alces alces).

A 5-years-old moose (Alces alces) cow kept in a zoo in the German Federal State of Brandenburg aborted a female foetus of 44cm crown rump length (CRL). Pathohistological analysis revealed several Neospora (N.) caninum infected cells and cysts, as well as multifocal gliosis, necrosis, haemorrhages, dystrophic mineralisation and haemosiderosis in the brain, predominantly in cerebrum and brainstem. In addition, mild lymphocytic meningitis was present. Together with the fresh foetus, a mummified foetus of 16cm CRL was expelled. Neither focal necrosis, nor inflammation was detected in the brain of the mummified foetus. By two polymerase chain reactions (PCR) targeting the pNc5 gene of N. caninum (i.e. an end point PCR and a real-time PCR), by two serological methods (immunofluorescence test and immunoblot), by histological and immunohistochemical analyses, transplacental N. caninum infection was confirmed in the fresh foetus and interpreted as possible cause of abortion. Infection with other agents causing abortion including Bovine Herpesvirus 1 (BHV1), Bluetongue Virus (BTV), Bovine Virus Diarrhoea Virus (BVDV), Brucella spp., Chlamydia spp., Coxiella burnetii and Toxoplasma gondii were excluded. Our findings show that control measures may be necessary to protect captive moose against accidental N. caninum infection. Further studies are needed to explore the importance of neosporosis in wild and captive moose.