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The purpose of this retrospective study was to evaluate the quality of outside hospital imaging and associated reports submitted to us for reinterpretation related to clinical care at our tertiary cancer center. We compared the initial study interpretations to that of interpretations performed by subspecialty-trained abdominal radiologists at our center and whether this resulted in a change in inpatient treatment.We performed an institutional review board-approved retrospective single-institution study of 915 consecutive outside computed tomography (CT) and magnetic resonance (MR) abdominal imaging studies that had been submitted to our institution between August 1, 2020 and November 30, 2020. The assessed parameters included the quality and accuracy of the report, the technical quality of the imaging compared to that at our institution, the appropriateness of the imaging for staging or restaging, usage of oral and IV contrast, and CT slice thickness. Clinical notes, pathologic findings, and subsequent imaging were used to establish an accurate diagnosis and determine the effect on clinical treatment. Discrepancies between the initial and secondary interpretations were identified independently by a panel of radiologists to assess changes in treatment. The impact of discrepancies on treatment was evaluated based on current treatment guidelines.Of 744 CT (81%) and 171 MR (19%) outside imaging studies, 65% had suboptimal quality compared to the images at our institution, and 31% were inappropriate for oncological care purposes. Only 21% of CT studies had optimal slice thickness of3 mm. Of 375 (41%) outside reports, 131 (34%) had discrepancies between secondary and initial interpretations. Of the 88 confirmed discrepant studies, 42 patients (48%) had a change in treatment based on the secondary interpretation.Imaging studies from outside institutions have variable image quality and are often inadequate for oncologic imaging. The secondary interpretations by subspecialty-trained radiologists resulted in treatment change.

The purpose of this prospective study was to determine whether the cost and cost-effectiveness of early rehabilitation after stroke are associated with the degree of initial disability. The data for cost calculations were collected by the bottom-up (micro-costing) method alongside the standard inpatient care. The total sample included 87 patients who were transferred from acute care to early rehabilitation unit of three participating stroke centers at the median time poststroke of 11 days (range 4-69 days). The study was pragmatic so that all hospitals followed their standard therapeutic procedures. For each patient, the staff recorded each procedure and the associated time over the hospital stay. The cost and cost-effectiveness were compared between four disability categories. The average cost of the entire hospitalization was CZK 114 489 (EUR 4348) with the daily average of CZK 5103 (EUR 194). The cost was 2.4 times higher for the immobile category (CZK/EU: 167 530/6363) than the self-sufficient category (CZK/EUR: 68 825/2614), and the main driver of the increase was the cost of nursing. The motor status had a much greater influence than cognitive status. We conclude that the cost and cost-effectiveness of early rehabilitation after stroke are positively associated with the degree of the motor but not cognitive disability. To justify the cost of rehabilitation and monitor its effectiveness, it is recommended to systematically record the elements of care provided and perform functional assessments on admission and discharge.

OBJECTIVE. The purpose of this study was to perform quantitative and qualitative evaluation of a deep learning image reconstruction (DLIR) algorithm in contrast-enhanced oncologic CT of the abdomen...

In recent years there have been a growing number of reports on applying viruses in oncological treatment. In the present study, we demonstrated for the first time that animal virus EHV-1 productively replicates in the human adenocarcinoma cell line (A549) without the need for adaptation. Real-time PCR analysis and immunofluorescence assay showed that EHV-1 could infect and causes lysis of human lung cancer cells. According to our results, we can assume that EHV-1 has oncolytic potential.

Induction with ibrutinib and rituximab provides an opportunity to minimise chemotherapy exposure, because upfront use of these targeted therapies could result in remission without chemotherapy and allow for consolidation with only four cycles of chemotherapy instead of the conventional eight. We aimed to determine the activity and safety of ibrutinib-rituximab induction followed by shortened chemoimmunotherapy (four cycles) with rituximab plus hyper-fractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone (R-HCVAD) alternating with methotrexate-cytarabine in previously untreated patients with mantle cell lymphoma.We did a single-centre, single-arm, phase 2 trial in previously untreated patients with mantle cell lymphoma. Eligible patients were aged 65 years or younger and had serum bilirubin of less than 1·5 mg/dL, creatinine clearance of 30 mL/min or more, Eastern Cooperative Oncology Group performance status of 2 or less, and cardiac ejection fraction 50% or more by echocardiogram. Patients received 12 cycles of ibrutinib-rituximab induction (part A; oral ibrutinib 560 mg daily and intravenous rituximab 375 mg/m131 patients were enrolled between June 12, 2015, and Dec 6, 2018. The median age was 56 years (IQR 49-60). 58 (50%) of 117 patients had high Ki-67 (≥30%). 129 (98%, 95% CI 95-100) of 131 patients had an overall response in part A. The most common grade 3-4 adverse events were lymphocytopenia (19 [14%] of 131), skin rash (16 [12%]), thrombocytopenia (12 [9%]), infections (11 [8%]), and fatigue (ten [8%]) in part A and lymphocytopenia (96 [73%]), leukocytopenia (42 [32%]), thrombocytopenia (40 [30%]), and neutropenia (26 [20%]) in part B. There was one on-study death, which was not deemed to be treatment-related.Induction with ibrutinib-rituximab in the frontline treatment of young patients with mantle cell lymphoma is active and safe. This approach allowed minimisation of the number of chemotherapy cycles, thereby reducing the adverse events associated with chemotherapy. Newer trials bringing the next-generation Bruton's tyrosine kinase inhibitors into the frontline setting might obviate the need for chemotherapy altogether in patients with mantle cell lymphoma.Pharmacyclics, Janssen.

PURPOSE: To evaluate colorectal cancer hepatic metastasis detection and characterization between reduced radiation dose (RD) and standard dose (SD) contrast material–enhanced CT of the abdomen and to qualitatively compare between filtered back projection (FBP) and iterative reconstruction algorithms. MATERIALS AND METHODS: In this prospective study (from May 2017 through November 2017), 52 adults with biopsy-proven colorectal cancer and suspected hepatic metastases at baseline CT underwent two portal venous phase CT scans: SD and RD in the same breath hold. Three radiologists, blinded to examination details, performed detection and characterization of 2–15-mm lesions on the SD FBP and RD adaptive statistical iterative reconstruction (ASIR)–V 60% series images. Readers assessed overall image quality and lesions between SD FBP and seven different iterative reconstructions. Two nonblinded consensus reviewers established the reference standard using the picture archiving and communication system lesion marks of each reader, multiple comparison examinations, and clinical data. RESULTS: RD CT resulted in a mean dose reduction of 54% compared with SD. Of the 260 lesions (233 metastatic, 27 benign), 212 (82%; 95% confidence interval [CI]: 76%, 86%) were detected with RD CT, whereas 252 (97%; 95% CI: 94%, 99%) were detected with SD (P < .001); per-lesion sensitivity was 79% (95% CI: 74%, 84%) and 94% (95% CI: 90%, 96%) (P < .001), respectively. Mean qualitative scores ranked SD images as higher quality than RD series images, and ASIR-V ranked higher than ASIR and Veo 3.0. CONCLUSION: CT evaluation of colorectal liver metastases is compromised with modest radiation dose reduction, and the use of iterative reconstructions could not maintain observer performance. © RSNA, 2018

OBJECTIVE This study aimed to evaluate the quality of enhancement and solid-organ lesion depiction using weight-based intravenous (IV) contrast dosing calculated by injector software versus fixed IV contrast dose in oncologic abdominal computed tomographic (CT) examinations. METHODS This institutional review board-exempt retrospective cohort study included 134 patients who underwent single-phase abdominal CT before and after implementation of weight-based IV contrast injector software. Patient weight, height, body mass index, and body surface area were determined. Two radiologists qualitatively assessed examinations (4 indicating markedly superior to -4 indicating markedly inferior), and Hounsfield unit measurements were performed. RESULTS Enhancement (estimated mean, -0.05; 95% confidence interval [CI], -0.19 to 0.09; P = 0.46) and lesion depiction (estimated mean, -0.01; 95% CI, -0.10 to 0.07; P = 0.79) scores did not differ between CT examinations using weight-based IV contrast versus fixed IV contrast dosing when a minimum of 38.5 g of iodine was used. However, the scores using weight-based IV contrast dosing were lower when the injector software calculated and delivered less than 38.5 g of iodine (estimated mean, -0.81; 95% CI, -1.06 to -0.56; P < 0.0001). There were no significant differences in measured Hounsfield units between the CT examinations using weight-based IV contrast dosing versus fixed IV contrast dosing. CONCLUSIONS Oncologic CT image quality was maintained or improved with weight-based IV contrast dosing using injector software when using a minimum amount of 38.5 g of iodine.

This article reviews the relevant anatomy, imaging features on computed tomography, magnetic resonance imaging, and management of common processes involving the sciatic foramen. The anatomy of the sciatic foramen is complex and provides an important conduit between the pelvis, gluteus, and lower extremity. This paper reviewed the anatomy, common pathologies, and imaging features of this region including trauma, infection, nerve entrapment, tumor spread, hernia, and vascular anomaly.

Background: SARS-CoV-2 reached Europe in early 2020 and disrupted the private and public life of its citizens, with potential implications for substance use. The objective of this study was to describe possible changes in substance use in the first months of the SARS-CoV-2 pandemic in Europe. Methods: Data were obtained from a cross-sectional online survey of 36,538 adult substance users from 21 European countries conducted between April 24 and July 22 of 2020. Self-perceived changes in substance use were measured by asking respondents whether their use had decreased (slightly or substantially), increased (slightly or substantially), or not changed during the past month. The survey covered alcohol (frequency, quantity, and heavy episodic drinking occasions), tobacco, cannabis, and other illicit drug use. Sample weighted data were descriptively analysed and compared across substances. Results: Across all countries, use of all substances remained unchanged for around half of the respondents, while the remainder reported either a decrease or increase in their substance use. For alcohol use, overall, a larger proportion of respondents indicated a decrease than those reporting an increase. In contrast, more respondents reported increases in their tobacco and cannabis use during the previous month compared to those reporting decreased use. No distinct direction of change was reported for other substance use. Conclusions: Our findings suggest changes in use of alcohol, tobacco and cannabis during the initial months of the pandemic in several European countries. This study offers initial insights into changes in substance use. Other data sources, such as sales statistics, should be used to corroborate these preliminary findings.

The mechanisms driving therapeutic resistance and poor outcomes of mantle cell lymphoma (MCL) are incompletely understood. We characterize the cellular and molecular heterogeneity within and across patients and delineate the dynamic evolution of tumor and immune cell compartments at single cell resolution in longitudinal specimens from ibrutinib-sensitive patients and non-responders. Temporal activation of multiple cancer hallmark pathways and acquisition of 17q are observed in a refractory MCL. Multi-platform validation is performed at genomic and cellular levels in PDX models and larger patient cohorts. We demonstrate that due to 17q gain, BIRC5/survivin expression is upregulated in resistant MCL tumor cells and targeting BIRC5 results in marked tumor inhibition in preclinical models. In addition, we discover notable differences in the tumor microenvironment including progressive dampening of CD8+ T cells and aberrant cell-to-cell communication networks in refractory MCLs. This study reveals diverse and dynamic tumor and immune programs underlying therapy resistance in MCL., Mantle cell lymphoma can be refractory to treatment. Here, the authors used single cell sequencing to study the tumours of patients that were responsive and resistant to treatment and find gains of 17q in resistant tumours, which they attribute to increased expression of Birc5 and validate these findings in mouse models of the disease.

OBJECTIVE: To optimize chest port contrast injections using step-wise improvements. METHODS: Ex-vivo injections were tested. 200 scans using power port injections were then evaluated. RESULTS: The highest flow rate was achieved using a 19G access needle, larger diameter tubing, and warmed contrast. The mean injection rates in baseline and post-improvement groups were 2.7 ± 0.4 mL/s and 4.8 ± 0.4 mL/s, respectively (P

Purpose/Objective Early stage Hodgkin lymphoma (ESHL) is highly curable, however 10-15% of patients experience relapse. We examined the utilization of follow-up imaging for ESHL patients who achieved a metabolic complete response after upfront therapy. Materials/Methods The records of adult patients treated at a single institution between 2003 and 2014 were reviewed. Positron emission tomography-computed tomography (PET-CT) and CT scan frequency was quantified during the 2 years following treatment and subsequent visits beyond 2 years. Results The study cohort contained 179 patients. The median age was 31 years; bulky disease was present in 30%. Doxorubicin, bleomycin, vinblastine and dacarbazine (ABVD) or AVD was given in 97%; 75% received radiation therapy. At a median follow up of 6.9 years, the 5-year progression-free (PFS) and overall survival (OS) rates were 93.7% and 98.1% respectively. Relapse occurred in 5% of patients (n=9) at a median of 9.1 months (range 4.6 – 27.2) from therapy. Two patients presented with symptoms prompting imaging in follow-up. Within 2 years after therapy, 376 PET-CT scans and 3325 CT scans were performed, yielding an average of 2.1 PET-CTs and 18.6 CTs per patient. Of the initial 179 patients, 113 had follow up conducted beyond 2 years post-therapy; an average of 2.7 PET-CTs and 33.2 CTs were performed. In the 2 year post therapy period, 463 scans were performed per relapse detected. Conclusion In this cohort of ESHL patients who responded completely to frontline therapy, the relapse rate was low. Routine imaging surveillance lacks clinical benefit in this patient population.

To qualitatively and quantitatively compare abdominal computed tomography (CT) images reconstructed with a new version of model-based iterative reconstruction (Veo 3.0; GE Healthcare) to those created with Veo 2.0.This retrospective study was approved by our institutional review board and was Health Insurance Portability and Accountability Act compliant. The raw data from 29 consecutive patients who had undergone CT abdomen scanning was used to reconstruct 4 sets of 3.75-mm axial images: Veo 2.0, Veo 3.0 standard, Veo 3.0 5% resolution preference (RP), and Veo 3.0 20% RP. A slice thickness optimization of 3.75 mm and texture feature was selected for Veo 3.0 reconstructions.The images were reviewed by 3 independent readers in a blinded, randomized fashion using a 5-point Likert scale and 5-point comparative scale.Multiple 2-dimensional circular regions of interest were defined for noise and contrast-to-noise ratio measurements. Line profiles were drawn across the 7 lp/cm bar pattern of the CatPhan 600 phantom for spatial resolution evaluation.The Veo 3.0 standard image set was scored better than Veo 2.0 in terms of artifacts (mean difference, 0.43; 95% confidence interval [95% CI], 0.25-0.6; P0.0001), overall image quality (mean difference, 0.87; 95% CI, 0.62-1.13; P0.0001) and qualitative resolution (mean difference, 0.9; 95% CI, 0.69-1.1; P0.0001). Although the Veo 3.0 standard and RP05 presets were preferred across most categories, the Veo 3.0 RP20 series ranked best for bone detail. Image noise and spatial resolution increased along a spectrum with Veo 2.0 the lowest and RP20 the highest.Veo 3.0 enhances imaging evaluation relative to Veo 2.0; readers preferred Veo 3.0 image appearance despite the associated mild increases in image noise. These results provide suggested parameters to be used clinically and as a basis for future evaluations, such as focal lesion detection, in the oncology setting.

Adrenal hyperplasia is non-malignant enlargement of the adrenal glands, which is often bilateral. It can be incidental or related to indolent disease process and may be related to benign or malignant etiologies causing biochemical alterations in the hypothalamic-pituitary-adrenal axis which controls steroidogenesis and in particular cortisol production. Clinical significance of the adrenal hyperplasia is variable ranging from asymptomatic finding to serious manifestations of Cushing syndrome. This is often associated with anatomical changes in the adrenal glands, which typically manifests as diffuse and sometimes nodular enlargement of the adrenal glands radiologically. Approaching adrenal hyperplasia requires careful clinical and biochemical evaluation in correlation with imaging review to differentiate ACTH-dependent and ACTH-independent etiologies. CT is the primary modality of choice for adult adrenal imaging owing to reproducibility, temporal and spatial resolution and broader access, while MRI often serves a complimentary role. Ultrasound and MRI are most commonly used in pediatric cases to evaluate congenital adrenal hyperplasia. This article will discuss the clinical presentation and imaging features of different types and mimics of adrenal cortical hyperplasia.

Summary Background Ibrutinib is approved in the EU, USA, and other countries for patients with mantle cell lymphoma who received one previous therapy. In a previous phase 2 study with single-agent ibrutinib, the proportion of patients who achieved an objective response was 68%; 38 (34%) of 111 patients had transient lymphocytosis. We hypothesised that adding rituximab could target mantle cell lymphoma cells associated with redistribution lymphocytosis, leading to more potent antitumour activity. Methods Patients with a confirmed mantle cell lymphoma diagnosis (based on CD20-positive and cyclin D1-positive cells in tissue biopsy specimens), no upper limit on the number of previous treatments received, and an Eastern Cooperative Oncology Group performance status score of 2 or less were enrolled in this single-centre, open-label, phase 2 study. Patients received continuous oral ibrutinib (560 mg) daily until progessive disease or unacceptable toxic effects. Rituximab 375 mg/m 2 was given intravenously once per week for 4 weeks during cycle 1, then on day 1 of cycles 3–8, and thereafter once every other cycle up to 2 years. The primary endpoint was the proportion of patients who achieved an objective response in the intention-to-treat population and safety assessed in the as-treated population. The study is registered with ClinicalTrials.gov, number NCT01880567, and is still ongoing, but no longer accruing patients. Findings Between July 15, 2013, and June 30, 2014, 50 patients were enrolled. Median age was 67 years (range 45–86), and the median number of previous regimens was three (range 1–9). At a median follow-up of 16·5 months (IQR 12·09–19·28), 44 (88%, 95% CI 75·7–95·5) patients achieved an objective response, with 22 (44%, 30·0–58·7) patients achieving a complete response, and 22 (44%, 30·0–58·7) a partial response. The only grade 3 adverse event in >=10% of patients was atrial fibrillation, which was noted in six (12%) patients. Grade 4 diarrhoea and neutropenia occurred in one patient each. Adverse events led to discontinuation of therapy in five (10%) patients (atrial fibrillation in three [6%] patients, liver infection in one [2%], and bleeding in one [2%]). Two patients died while on-study from cardiac arrest and septic shock; the latter was deemed possibly related to treatment. Interpretation Ibrutinib combined with rituximab is active and well tolerated in patients with relapsed or refractory mantle cell lymphoma. Our results provide preliminary evidence for the activity of this combination in clinical practice. A phase 3 trial is warranted for more definitive data. Funding Pharmacyclics LLC, an AbbVie Company.

We assessed differences in primary sites and spread patterns of the intestinal and diffuse subtypes of gastric carcinoma. We also compared survival outcomes based on spread patterns.For this retrospective IRB-approved study, our institutional imaging database was mined for patients with gastric cancer. We included 99 treatment-naïve patients. Patient demographics, pathologic data, tumor classification, primary tumor site, and metastasis sites were recorded. Pearson's chi-squared test was used to correlate tumor pathology with metastatic sites. Kaplan-Meier survival curves were compared between baseline metastatic types. A heat map was created based on the relative frequencies of metastatic sites for each primary tumor site.Of the 99 patients, 66 patients had intestinal and 33 had diffuse gastric carcinoma. The intestinal subtype was significantly associated with hepatic metastases (p 0.001). Diffuse subtype was associated with peritoneal metastases, including omental metastases (p 0.006), gastrosplenic ligament involvement (p 0.004), and mesocolonic implants (p 0.008). Patients with primary gastric tumors occurring at the greater curvature had longer overall survival than those with primary sites at the antrum, GE junction and lesser curvature (p = 0.0015). Patients with peritoneal metastases had a significantly shorter overall survival than patients without peritoneal metastases (p 0.001). Patients without mesocolon, gastrohepatic ligament, and gastrosplenic ligament involvement had a better survival (p = 0.005, p = 0.0002, and p = 0.0005, respectively). Presence of hepatic metastases had no effect on survival (p = 0.16).Recognizing distinctive spread patterns for intestinal versus diffuse gastric carcinoma can aid radiologists in diagnosis and guide clinical management.

BackgroundPatients with comorbid depression and personality disorders suffer from a heavy disease burden while tailored treatment options are limited, accounting for a high psychological and economic burden. Little is known about the effect of treatment dosage and type of psychotherapy for this specific co-morbid patient population, in terms of treatment-effect and cost-effectiveness. This study aims to compare treatment outcome of 25 versus 50 individual therapy sessions in a year. We expect the 50-session condition to be more effective in treating depression and maintaining the effect. Secondary objectives will be addressed in order to find therapy-specific and non-specific mechanisms of change.MethodsIn a mono-center pragmatic randomized controlled trial with a 2 × 2 factorial design, 200 patients with a depressive disorder and personality disorder(s) will be included. Patients will be recruited from a Dutch mental health care institute for personality disorders. They will be randomized over therapy dosage (25 vs 50 sessions in a year) and type of therapy (schema therapy vs short-term psychodynamic supportive psychotherapy). The primary clinical outcome measure will be depression severity and remission. Changes in personality functioning and quality of life will be investigated as secondary outcomes. A priori postulated effect moderators and mediators will be collected as well. All patients are assessed at baseline and at 1, 2, 3, 6, 9–12 months (end of therapy) and at follow up (6 and 12 months after end of treatment). Alongside the trial, an economic evaluation will be conducted. Costs will be collected from a societal perspective.DiscussionThis trial will be the first to compare two psychotherapy dosages in patients with both depression and personality disorders. Insight in the effect of treatment dosage for this patient group will contribute to both higher treatment effectiveness and lower costs. In addition, this study will contribute to the limited evidence base on treating patients with both depression and personality disorders. Understanding the processes that account for the therapeutic changes could help to gain insight in what works for whom.Trial registrationThis trial has been registered on July 20th 2016, Netherlands Trial Register, part of the Dutch Cochrane Centre (NTR5941).

The purpose of this study was to compare abdominopelvic computed tomography images reconstructed with adaptive statistical iterative reconstruction-V (ASIR-V) with model-based iterative reconstruction (Veo 3.0), ASIR, and filtered back projection (FBP).Abdominopelvic computed tomography scans for 36 patients (26 males and 10 females) were reconstructed using FBP, ASIR (80%), Veo 3.0, and ASIR-V (30%, 60%, 90%). Mean ± SD patient age was 32 ± 10 years with mean ± SD body mass index of 26.9 ± 4.4 kg/m. Images were reviewed by 2 independent readers in a blinded, randomized fashion. Hounsfield unit, noise, and contrast-to-noise ratio (CNR) values were calculated for each reconstruction algorithm for further comparison. Phantom evaluation of low-contrast detectability (LCD) and high-contrast resolution was performed.Adaptive statistical iterative reconstruction-V 30%, ASIR-V 60%, and ASIR 80% were generally superior qualitatively compared with ASIR-V 90%, Veo 3.0, and FBP (P0.05). Adaptive statistical iterative reconstruction-V 90% showed superior LCD and had the highest CNR in the liver, aorta, and, pancreas, measuring 7.32 ± 3.22, 11.60 ± 4.25, and 4.60 ± 2.31, respectively, compared with the next best series of ASIR-V 60% with respective CNR values of 5.54 ± 2.39, 8.78 ± 3.15, and 3.49 ± 1.77 (P0.0001). Veo 3.0 and ASIR 80% had the best and worst spatial resolution, respectively.Adaptive statistical iterative reconstruction-V 30% and ASIR-V 60% provided the best combination of qualitative and quantitative performance. Adaptive statistical iterative reconstruction 80% was equivalent qualitatively, but demonstrated inferior spatial resolution and LCD.

To compare studies with and without oral contrast on performance of multidetector computed tomography (CT) and the order to CT examination turnaround time in cancer patients presenting to the emergency department (ED). To the best of our knowledge, oral contrast utility has not previously been specifically assessed in cancer patients presenting to the emergency department. Retrospective review of CT abdomen examinations performed in oncology patients presenting to the emergency department during one month. CT examinations performed with and without oral contrast were rated by two consensus readers for degree of confidence and diagnostic ability. Correlations were assessed for primary cancer type, age, sex, chief complaint/examination indication, body mass index, intravenous contrast status, repeat CT examination within 4 weeks, and disposition. Turnaround times from order to the start of the CT examination were calculated. The studied group consisted of 267 patients (127 men and 140 women) with a mean age of 56 years and a mean body mass index of 27.8 kg/m2. One hundred sixty CT examinations were performed without oral contrast, and 107 CT examinations were performed with oral contrast. There was no significant difference between cases with oral contrast and cases without oral contrast in the number of cases rated as “improved confidence” (odds ratio [OR] 0.54, 95% confidence interval [CI] 0.23–1.31, P = 0.17), “improved diagnosis” (OR 0.58, 95% CI 0.20–1.64, P = 0.3), “impaired confidence” (OR 3.92, 95% CI 0.46–33.06, P = 0.21), or “impaired diagnosis” (OR 2.63, 95% CI 0.29–23.89, P = 0.39). The turnaround time in the group receiving oral contrast (mean, 141 min; standard deviation, 49.8 min) was significantly longer than that in the group not receiving oral contrast (mean, 109.2 min; standard deviation, 64.8 min) with a mean difference of 31.8 min (P

To qualitatively and quantitatively compare abdominal CT images reconstructed with a newversion of model-based iterative reconstruction (Veo 3.0; GE Healthcare Waukesha, WI) utilizing varied presetsof resolution preference, noise reduction and slice optimization.This retrospective study was approved by our Institutional Review Board and was Health Insurance Portability and Accountability Act compliant. The raw datafrom 30 consecutive patients who had undergone CT abdomen scanning were used to reconstructfour clinical presets of 3.75mm axial images using Veo 3.0: 5% resolution preference (RP05n), 5%noise reduction (NR05) and 40% noise reduction (NR40) with new 3.75mm "sliceoptimization," as well as one set using RP05 with conventional 0.625mm "slice optimization" (RP05c). The images were reviewed by two independent readers in a blinded, randomized manner using a 5-point Likert scale as well as a 5-point comparative scale. Multiple two-dimensional circular regions of interest were defined for noise and contrast-to-noise ratio measurements. Line profiles were drawn across the 7 lp cmThe NR05 image set was ranked as the best series in overall image quality (mean difference inrank 0.48, 95% CI [0.081-0.88], p = 0.01) and with specific reference to liver evaluation (meandifference 0.46, 95% CI [0.030-0.89], p = 0.03), when compared with the secondbest series ineach category. RP05n was ranked as the best for bone evaluation. NR40 was ranked assignificantly inferior across all assessed categories. Although the NR05 and RP05c image setshad nearly the same contrast-to-noise ratio and spatial resolution, NR05 was generally preferred. Image noise and spatial resolution increased along a spectrum with RP05n the highest and NR40the lowest. Compared to RP05n, the average noise was 21.01% lower for NR05, 26.88%lower for RP05c and 50.86% lower for NR40.Veo 3.0 clinical presets allow for selection of image noise and spatial resolution balance; for contrast-enhanced CT evaluation of the abdomen, the 5% noise reduction preset with 3.75 mm slice optimization (NR05) was generally ranked superior qualitatively and, relative to other series, was in the middle of the spectrum with reference to image noise and spatial resolution. Advances in knowledge: To our knowledge, this is the first study of Veo 3.0 noise reduction presets and varied slice optimization. This study provides insight into the behaviour of slice optimization and documents the degree of noise reduction and spatial resolution changes that users can expect across various Veo 3.0 clinical presets. These results provide important parameters to guide preset selection for both clinical and research purposes.

Adrenal cortical hyperplasia manifests radiologically as a non-malignant growth, or enlargement, of the adrenal glands, specifically the cortex, although the cortex cannot be definitively identified by conventional imaging. Controlled by the pituitary gland, the adrenal cortex drives critical processes, such as the production of cortisol, mineralocorticoid and sex hormones. Any disruption in the multiple enzymes and hormones involved in these pathways may cause serious or life-threatening symptoms, often associated with anatomical changes in the adrenal glands. Diagnosis and treatment of adrenal cortical hyperplasia requires a thorough clinical evaluation. As imaging has become more robust so has its role in the diagnosis and treatment of adrenal conditions. CT has been the primary modality for adrenal imaging owing to reproducibility, temporal and spatial resolution and broad access. MRI serves a complimentary role in adrenal imaging and can be used to further evaluate indeterminate CT findings or serve as an adjunct tool without the use of ionizing radiation. Ultrasound and fluoroscopy (genitography) are most commonly used in children and foetuses to evaluate congenital adrenal hyperplasia. This article will discuss the clinical presentation, laboratory workup and imaging features of adrenal cortical hyperplasia, both congenital and acquired.

Cushing syndrome (CS) is a constellation of clinical signs and symptoms resulting from chronic exposure to excess cortisol, either exogenous or endogenous. Exogenous CS is most commonly caused by administration of glucocorticoids. Endogenous CS is subdivided into two types: adrenocorticotropic hormone (ACTH) dependent and ACTH independent.Cushing disease, which is caused by a pituitary adenoma, is the most common cause of ACTH-dependent CS for which pituitary MRI can be diagnostic, with bilateral inferior petrosal sinus sampling useful in equivocal cases. In ectopic ACTH production, which is usually caused by a tumor in the thorax (e.g., small cell lung carcinoma, bronchial and thymic carcinoids, or medullary thyroid carcinoma) or abdomen (e.g., gastroenteropancreatic neuroendocrine tumors or pheochromocytoma), CT, MRI, and nuclear medicine tests are used for localizing the source of ACTH. In ACTH-independent CS, which is caused by various adrenal abnormalities, adrenal protocol CT or MRI is usually diagnostic.

To determine whether the qualitative sonographic appearance of slow deep venous flow in the lower extremities correlates with quantitative slow flow and an increased risk of deep venous thrombosis (DVT) in oncology patients.In this Institutional Review Board-approved retrospective study, we reviewed lower extremity venous Doppler sonographic examinations of 975 consecutive patients: 482 with slow flow and 493 with normal flow. The subjective slow venous flow and absence of initial DVT were confirmed by 2 radiologists. Peak velocities were recorded at 3 levels. Each patient was followed for DVT development. The associations between DVT and the presence of slow venous flow were examined by the Fisher exact test; a 2-sample t test was used for peak velocity and DVT group comparisons. The optimal cutoff peak velocity for correlation with the radiologists' perceived slow flow was determined by the Youden index.Deep venous thrombosis development in the slow-flow group (21 of 482 [4.36%]) was almost doubled compared with patients who had normal flow (11 of 493 [2.23%]; P = .0456). Measured peak venous velocities were lower in the slow-venous flow group (P.001). Patients with subsequent DVT did not have a significant difference in venous velocities compared with their respective patient groups. The sum of 3 venous level velocities resulted in the best cutoff for dichotomizing groups into normal versus slow venous flow.Qualitative slow venous flow in the lower extremities on Doppler sonography accurately correlates with quantitatively slower flow, and this preliminary evaluation suggests an associated mildly increased rate of subsequent DVT development in oncology patients.

The field of cancer genomics is rapidly evolving and has led to the development of new therapies. Knowledge of commonly involved cellular pathways and genetic mutations is now essential for radiologists reading oncology cases. Radiogenomics is an emerging area of research that seeks to correlate imaging features with cancer genotypes. Such knowledge may extend the utility of multiparametric imaging to yield information regarding cancer prognosis and likelihood of therapeutic response. To date, only a handful of radiogenomics studies have been performed to evaluate solid tumors of the body, and there is much to explore. Before doing so, however, it behooves us to have adequate background knowledge of clinical cancer genomics to design meaningful radiogenomics projects and explore imaging phenotypes. Herein, an up-to-date, detailed overview is provided of well-known and common mutations of solid body tumors (such as human epithelial growth factor receptor 2, breast cancer susceptibility protein), newer genomic alterations with potential for clinical relevance, and a discussion of known related imaging findings, including existing radiogenomics data and other radiologic patterns of disease.

To determine the inter- and intra-reader agreement of size, conspicuity, and margin sharpness of pancreatic adenocarcinoma on monochromatic, polychromatic, and iodine map dual-energy CT (DECT) images. Retrospective review of DECT images from 61 patients with untreated pancreatic adenocarcinoma was performed by three radiologists independently. Pancreatic parenchymal phase images were generated as 50 and 70 keV, 140 kVp quality control (QC), and iodine map images. These were analyzed in a blinded randomized order during four reading sessions separated by 5–7 days. For each image set, readers recorded the longest axial and perpendicular primary tumor dimensions, and qualitatively scored tumor conspicuity and edge sharpness on 5-point scales. Linear mixed model was used to estimate and compare tumor measurements, tumor conspicuity, and tumor edge sharpness scores between readers and image sets. Kappa statistics were used to determine inter-observer agreement for tumor conspicuity and edge sharpness. The range of tumor measures (mean of longest dimension ± standard deviation) was 3.18 ± 1.41 to 3.83 ± 1.57 cm. Reproducibility of tumor measurements was very high with mild variability (s 2 = 0.01–0.10) between readers for the different image sets. Inter-observer agreement values for tumor conspicuity (κ = 0.01–0.17) and edge sharpness (κ = 0.12–0.25) were low for all image sets, although two of three readers scored tumor conspicuity and edge sharpness higher on monochromatic and iodine map DECT images than on 140 kVp QC images (p

Accumulating evidence documents the efficacy of Therapeutic Assessment (TA) in terms of symptom reduction and other outcomes, but only minimal data speak to the patient's perspective of what is memorable, or potentially important, about this intervention. In line with the humanistic and phenomenological philosophy of TA, we solicited patient input by asking personality disorder (PD) patients who participated in a recent randomized controlled trial (De Saeger et al., 2014 ) about their experiences. We report on 10 PD patients who were administered semistructured interviews designed to assess an in-depth perspective of undergoing TA. Our methodological approach can be described as phenomenological and integrative, approximating guidelines provided by the Consensual Qualitative Research paradigm (Hill, 2012 ). Four core content domains emerged from the transcribed and coded interview protocols: (a) relationship aspects, (b) new insight into personal dynamics, (c) sense of empowerment, and (d) validation of self. Novel experiences were mostly of a relational nature, and pertained to feeling of being treated like an equal and essential partner in a highly individualized venture. Research and clinical implications of these patient reports of TA participation are discussed.

Summary Background The combination of rituximab and lenalidomide has shown promise for the treatment of mantle-cell lymphoma (MCL) in preclinical studies. We aimed to identify the maximum tolerated dose (MTD) of lenalidomide when combined with rituximab in a phase 1 trial and to assess the efficacy and safety of this combination in a phase 2 trial in patients with relapsed or refractory MCL. Methods Patients with relapsed or refractory MCL who had received one to four previous lines of treatment were enrolled in this single-arm, open-label, phase 1/2 trial at MD Anderson Cancer Center. In phase 1, to identify the MTD of lenalidomide, four patient cohorts received escalating doses (10, 15, 20, and 25 mg) of daily oral lenalidomide on days 1–21 of each 28-day cycle. 375 mg/m 2 intravenous rituximab was also administered in four weekly doses during cycle 1 only. In phase 2, patients received rituximab plus the MTD of lenalidomide, following the same cycles as for phase 1. Treatment in both phases continued until disease progression, stem-cell transplantation, or severe toxicity. The primary efficacy endpoint was overall response (complete or partial response). The secondary efficacy endpoint was survival. We used the Kaplan-Meier method to estimate response duration, progression-free survival, and overall survival. Analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00294632. Findings 52 patients were enrolled between Feb 10, 2006 and July 30, 2009, 14 in phase 1 and 44 (including six patients who received the MTD of lenalidomide in the phase 1 portion) in phase 2. The MTD was 20 mg lenalidomide. One patient who was treated with 25 mg lenalidomide developed a grade 4 non-neutropenic infection and died. In the phase 2 portion of the study, grade 3–4 haematological toxicities included neutropenia (29 patients), lymphopenia (16 patients), leucopenia (13 patients), and thrombocytopenia (ten patients). There were only two episodes of febrile neutropenia. Among 44 patients in phase 2, 25 (57%) had an overall response: 16 (36%) had a complete response and nine (20%) had a partial response. The median response duration was 18·9 months (95% CI 17·0 months to not reached [NR]). The median progression-free survival was 11·1 months (95% CI 8·3 to 24·9 months), and the median overall survival was 24·3 months (19·8 months to NR). Five of 14 patients who had received bortezomib treatment before enrolment achieved an overall response. Interpretation Oral lenalidomide plus rituximab is well tolerated and effective for patients with relapsed or refractory MCL. Funding Celgene.

A 36-year-old woman presented to her primary care physician with right lower abdominal pain. Her physician subsequently requested a CT to rule out appendicitis. Contrast-enhanced CT was performed and revealed no evidence of appendicitis but showed two subcutaneous ovoid soft-tissue masses anterior to the rectus sheath in the upper pelvis. Pelvic MRI confirmed the two masses, which showed mild enhancement. The objective of this article is to discuss a diagnostic approach to subcutaneous soft-tissue masses in the abdominal wall. Diagnosis was endometriosis of the abdominal wall.Integrating salient imaging findings with clinical history is crucial when approaching the diagnosis of subcutaneous soft-tissue masses. The diagnosis of endometriosis should be entertained when soft-tissue masses are seen in the distribution of a cesarean section scar in a woman of reproductive age. Pain, particularly with a cyclic pattern, is highly suggestive of endometriosis. If endometriosis is suspected on CT or ultrasound, MRI can be performed for further evaluation. Definitive diagnosis is made with biopsy. Because subcutaneous nodules are so amenable percutaneous biopsy, imaging features, although of interest, are somewhat ancillary to the diagnostic workup.

Background: No previous studies have compared the effectiveness of different modalities of psychotherapeutic treatment, as defined by different settings and durations, for patients with cluster C personality disorders. The aim of this multicentre study was to compare the effectiveness of 5 treatment modalities for patients with cluster C personality disorders in terms of psychiatric symptoms, psychosocial functioning, and quality of life. The following treatment modalities were compared: long-term outpatient (more than 6 months), short-term day hospital (up to 6 months), long-term day hospital, short-term inpatient, and long-term inpatient psychotherapy. Methods: The study was conducted between March 2003 and June 2008 in 6 mental health care centres in the Netherlands, with a sample of 371 patients with a DSM-IV-TR axis-II cluster C diagnosis. Patients were assigned to 5 different modalities of psychotherapeutic treatment, and effectiveness was assessed at 12 months after baseline. An intention-to-treat analysis was conducted for psychiatric symptoms (Brief Symptom Inventory), psychosocial functioning (Outcome Questionnaire-45), and quality of life (EQ-5D), using multilevel statistical modelling. As the study was non-randomised, the propensity score method was used to control for initial differences. Results: Patients in all treatment groups had improved on all outcomes 12 months after baseline. Patients receiving short-term inpatient treatment showed more improvement than patients receiving other treatment modalities. Conclusions: Psychotherapeutic treatment, especially in the short-term inpatient modality, is an effective treatment for patients with cluster C personality disorders.

Background and Objective: The propensity score method (PS) has proven to be an effective tool to reduce bias in nonrandomized studies, especially when the number of (potential) confounders is large and dimensionality problems arise. The PS method introduced by Rosenbaum and Rubin is described in detail for studies with 2 treatment options. Since in clinical practice we are often interested in the comparison of multiple interventions, there was a need to extend the PS method to multiple treatments. It has been shown that in theory a multiple PS method is possible. So far, its practical application is rare and a practical introduction lacking.Methods: A practical guideline to illustrate the use of the multiple PS method is provided with data from a mental health study. The multiple PS is estimated with a multinomial logistic regression analysis. The multiple PS is the probability of assignment to each treatment category. Subsequently, to estimate the treatment effects while controlling for initial differences, the multiple PSs, calculated for each treatment category, are included as extra predictors in the regression analysis.Results: With the multiple PS method, balance was achieved in all relevant pretreatment variables. The corrected estimated treatment effects were somewhat different from the results without control for initial differences.Conclusions: Our results indicate that the multiple PS method is a feasible method to adjust for observed pretreatment differences in nonrandomized studies where the number of pretreatment differences is large and multiple treatments are compared.

Aim: To describe the use of diagnostic labels by clinicians for children with autism spectrum disorders (ASD) and calculate the label-specific and overall agreement between diagnostic labels and Diagnostic and Statistical Manual of Mental Disorders – Fourth Edition (DSM-IV) diagnoses provided by the same clinician. Methods: State-wide active surveillance was used to ascertain children newly recognised with one or more DSM-IV criteria for autistic disorder aged 0–15 years (incident cases) in New South Wales (NSW) between July 1999 and December 2000. Clinicians were asked to supply a diagnostic label and then complete DSM-IV criteria for each child reported. Results: Questionnaires with diagnostic label and DSM-IV criteria were returned for 348 children. The agreement between labels used and diagnosis based on DSM-IV classification system was the highest for autism (97%) and lower for labels of Asperger disorder, pervasive developmental disorder – not otherwise specified or atypical autism (27%). Kappa overall agreement was 0.31. Level of agreement between label and DSM-IV diagnosis was similar for questionnaires completed by multidisciplinary teams, psychiatrists, paediatricians and psychologists working as part of a team. Conclusion: A lack of agreement between the diagnostic labelling used by clinicians and diagnosis based on DSM-IV criteria indicates a lack of consistency in diagnostic communication that is necessary to provide best clinical care, appropriate services and relevant information to parents and carers.

Plasma leptin concentrations are markedly reduced in malnourished patients with anorexia nervosa (AN). Whether the long-term underweight and low-fat stores affect the leptin response to exercise remains unknown. We investigated the effect of 45-minute cycle ergometer exercise (2 W kg−1 of lean body mass [LBM]) on plasma leptin, norepinephrine (NE), glycerol, and insulin levels in 10 patients with AN and in 15 healthy age-matched women (C). Plasma leptin levels immediately and 90 minutes after the exercise bout were significantly reduced compared with basal leptin levels in both AN and C groups (P < .05). Compared with the control trial, leptin levels were significantly lower immediately and 90 minutes after exercise in the AN group (P < .05) but not in the C group. Basal and exercise-induced plasma glycerol and NE levels did not differ significantly between the groups. Basal and exercise-induced plasma insulin levels were significantly lower in the AN group compared with the C group (P < .05). In conclusion, we demonstrated that a single bout of low-intensity exercise significantly reduces plasma leptin levels in patients with AN. In healthy women, exercise had no effect on lowering leptin concentrations beyond the diurnal decrease that occurs in the absence of exercise. Neither NE nor insulin are responsible for the different response of leptin to exercise in AN.

Objective: Our aim was to demonstrate the feasibility of the univariate and generalized propensity score (PS) method in subgroup analysis of outcomes research. Methods: First, to estimate subgroup effects, we tested the performance of 2 different PS methods, using Monte Carlo simulations: (1) the univariate PS with additional adjustment on the subgroup; and (2) the generalized PS, estimated by crossing the treatment options with a subgroup variable. The subgroup effects were estimated in a linear regression model using the 2 PS adjustments. We further explored whether the subgroup variable should be included in the univariate PS. Second, the 2 methods were compared using data from a large effectiveness study on psychotherapy in personality disorders. Using these data we tested the differences between short-term and long-term treatment, with the severity of patients' problems defining the subgroups of interest. Results: The Monte Carlo simulations showed minor differences between both PS methods, with the bias and mean squared error overall marginally lower for the generalized PS. When considering the univariate PS, the subgroup variable can be excluded from the PS estimation and only adjusted for in the outcome equation. When applied to the psychotherapy data, the univariate and generalized PS estimations gave similar results. Conclusion: The results support the use of the generalized PS as a feasible method, compared with the univariate PS, to find certain subgroup effects in nonrandomized outcomes research.

This is the first reported study of a riverbank filtration (RBF) scheme to be assessed following the Australian Guidelines for Managed Aquifer Recharge. A comprehensive staged approach to assess the risks from 12 hazards to human health and the environment has been undertaken. Highest risks from untreated ground and Ganga River water were identified with pathogens, turbidity, iron, manganese, total dissolved solids and total hardness. Recovered water meets the guideline values for inorganic chemicals and salinity but exceeds limits for thermotolerant coliforms frequently. A quantitative microbial risk assessment undertaken on the water recovered from the aquifer indicated that the residual risks of 0.00165 disability-adjusted life years (DALYs) posed by the reference bacteria Escherichia coli O157:H7 were below the national diarrhoeal incidence of 0.027 DALYs and meet the health target in this study of 0.005 DALYs per person per year, which corresponds to the World Health Organization (WHO) regional diarrhoeal incidence in South-East Asia. Monsoon season was a major contributor to the calculated burden of disease and final DALYs were strongly dependent on RBF and disinfection pathogen removal capabilities. Finally, a water safety plan was developed with potential risk management procedures to minimize residual risks related to pathogens.

Our purpose was to evaluate the sensitivity of multidetector CT for the detection of peritoneal metastases between standard 2.5 mm axial imaging and maximum-intensity-projection (MIP) reconstructions.The Institutional Review Board approved this retrospective study and waived the need to obtain patient consent. We retrospectively identified 36 patients with pancreatic adenocarcinoma and peritoneal metastatic disease who underwent a pancreatic protocol CT examination of the abdomen and pelvis between January 2012 and January 2014. Three independent radiologists reviewed a randomized combination of standard axial (2.5 mm reconstructed thickness, 2.5 mm interval) and axial MIP reconstructions (6, 3 mm interval) over two sessions. Each reader recorded metastasis location in PACS. Subsequent consensus review by two radiologists determined the final number and size of metastases.The reviewers found 328 peritoneal implants in 36 patients. After accounting for the size, location, and number of lesions as well as multiple readers, a generalized estimating equations model showed that the statistical combination of MIP with standard technique significantly increased the odds of correctly identifying a lesion (OR 2.16; 95% CI 1.86-2.51; p value 0.0001) compared to standard technique alone. MIP reconstruction as a standalone technique was less sensitive compared to standard technique alone (OR 0.81; 95% CI 0.65-0.99; p value = 0.0468). When compared to standard axial imaging, evaluation via MIP reconstructions resulted in the identification of an additional 50 (15%), 45 (14%), and 55 (17%) lesions by Readers 1-3, respectively.The axial 6 mm MIP series is complimentary in the CT evaluation of peritoneal metastases. MIP reconstruction evaluation identified a significant number of additional lesions, but is not adequate as a standalone technique for peritoneal cavity assessment.

Thyroid function plays an important role in the regulation of overall metabolic rate and lipid metabolism. However, it is uncertain whether thyroid hormones directly affect lipolysis in adipose tissue and to what extent those changes contribute to overall metabolic phenotype. Our study was designed, using the microdialysis technique, to determine basal and isoprenaline-stimulated local lipolysis and to determine local concentrations of lipolysis-regulating catecholamines in abdominal subcutaneous adipose tissue in 12 patients with hypothyroidism, 6 patients with hyperthyroidism, and 12 healthy control subjects. Plasma norepinephrine (NE) concentrations in hypothyroid subjects were significantly higher than in the control and hyperthyroid groups. In contrast, systemic, adipose NE levels in hypothyroid patients were decreased relative to controls. Hyperthyroidism, on the other hand, resulted in four-fold higher adipose NE levels. Basal lipolysis measured by glycerol concentrations in adipose tissue was significantly attenuated in hypothyroid patients and markedly increased in hyperthyroid patients in comparison with the control group. In addition to differences in basal lipolysis, hypothyroidism resulted in attenuated, and hyperthyroidism in enhanced, lipolytic response to local stimulation with beta(1,2)-adrenergic agonist isoprenaline. These results demonstrate that lipolysis in abdominal subcutaneous adipose tissue is strongly modulated by thyroid function. We suggest that thyroid hormones regulate lipolysis primarily by affecting local NE concentration and/or adrenergic postreceptor signaling.

Thyroid hormones play a major role in lipid metabolism. However, whether they directly affect lipolysis locally in the adipose tissue remains unknown. Therefore, we measured abdominal sc adipose tissue norepinephrine (NE), basal, and isoprenaline-stimulated lipolysis in 12 hypothyroid patients (HYPO), six hyperthyroid patients (HYPER), and 12 healthy controls by in vivo microdialysis.Adipose tissue NE was decreased in HYPO and increased in HYPER compared with controls (90.4 ± 2.9 and 458.0 ± 69.1 vs. 294.9 ± 19.5 pmol/liter, P < 0.01). Similarly, basal lipolysis, assessed by glycerol assay, was lower in HYPO and higher in HYPER than in controls (88.2 ± 9.9 and 566.0 ± 42.0 vs. 214.3 ± 5.1 μmol/liter P < 0.01). The relative magnitude of isoprenaline-induced glycerol increase was smaller in HYPO (39 ± 19.4%, P < 0.05 vs. basal) and higher in HYPER (277 ± 30.4%, P < 0.01) than in controls (117 ± 5.6%, P < 0.01). The corresponding changes in NE after isoprenaline stimulation were as follows: 120 ± 9.2% (P < 0.05), 503 ± 113% (P < 0.01), and 267 ± 17.2 (P < 0.01).In summary, by affecting local NE levels and adrenergic postreceptor signaling, thyroid hormones may influence the lipolysis rate in the abdominal sc adipose tissue.

Studies have shown that ghrelin plays a major role in energy homeostasis and modulation of feeding behavior. However, little is known about the influence of food consumption on plasma ghrelin levels in humans. Therefore, we investigated responses of plasma ghrelin to food intake, meal volume and meal nutritional value in healthy volunteers and women with anorexia nervosa (AN). After overnight fasting, all subjects received either a standardized breakfast or fiber. Plasma ghrelin levels were measured before and after the meal. Fasting plasma ghrelin was significantly higher in AN patients than in controls (1,800.6 +/- 47.0 vs. 795.9 +/- 24.3 pg/ml, P0.001) (606.8 +/- 15.8 vs. 268.2 +/- 8.2 pmol/l, P0.001), and correlated negatively with percentage of body fat in both groups. Ghrelin levels markedly fell after consumption of either a standardized meal or fiber in controls, but not in anorexic women. Thus, we concluded that the acute plasma ghrelin response to food intake, which in healthy individuals is independent of meal caloric value, is impaired in women with AN. This abnormality may be part of a chronic adaptation to prolonged food restriction, which attempts to restore a normal feeding conduct by maintaining the drive to eat.

Since the Journal of Paediatrics and Child Health was first published, there has been substantial change in the field of autism spectrum disorders (ASDs) with an exponential increase in the amount of funded and published research. In this paper, we focus on regression in children with ASD, a phenomenon that remains poorly understood. We discuss the implications of what we know about regression in ASD for the way we think about ASD more broadly and for paediatric practice.

Vaccination to protect against human infectious diseases may be enhanced by using adjuvants that can selectively stimulate immunoregulatory responses. In a murine model, a novel nanoparticulate adjuvant composed of calcium phosphate (CAP) was compared with the commonly used aluminum (alum) adjuvants for its ability to induce immunity to herpes simplex virus type 2 (HSV-2) and Epstein-Barr virus (EBV) infections. Results indicated that CAP was more potent as an adjuvant than alum, elicited little or no inflammation at the site of administration, induced high titers of immunoglobulin G2a (IgG2a) antibody and neutralizing antibody, and facilitated a high percentage of protection against HSV-2 infection. Additional benefits of CAP include (i) an insignificant IgE response, which is an important advantage over injection of alum compounds, and (ii) the fact that CAP is a natural constituent of the human body. Thus, CAP is very well tolerated and absorbed. These studies were performed with animal models. By virtue of the potency of this CAP adjuvant and the relative absence of side effects, we believe that this new CAP formulation has great potential for use as an adjuvant in humans.

Profound changes in the metabolism of eicosanoids with increased concentrations of free arachidonic acid (AA) and its proinflammatory metabolites have been observed in psoriatic lesions. Free eicosapentaenoic acid (EPA) may compete with liberated AA and result in an antiinflammatory effect.Our purpose was to assess the efficacy and safety of intravenously administered fish-oil-derived lipid emulsion on chronic plaque-type psoriasis.A double-blind, randomized, parallel group study was performed in eight European centers. Eighty-three patients hospitalized for chronic plaque-type psoriasis with a severity score of at least 15 according to the Psoriasis Area and Severity Index (PASI) participated in a 14-day trial. They were randomly allocated to receive daily infusions with either a omega-3 fatty acid-based lipid emulsion (Omegavenous; 200 ml/day with 4.2 gm of both EPA and docosahexaenoic acid (DHA); 43 patients) or a conventional omega-6-lipid emulsion (Lipovenous; EPA+DHA0.1 gm/100 ml; 40 patients). The groups were well matched with respect to demographic data and psoriasis-specific medical history. Efficacy of therapy was evaluated by changes in PASI, in an overall assessment of psoriasis by the investigator, and a self-assessment by the patient. In one center neutrophil 4- versus 5-series leukotriene (LT) generation and platelet 2- versus 3- thromboxane generation were investigated and plasma-free fatty acids were determined.The total PASI score decreased by 11.2 +/- 9.8 in the omega-3 group and by 7.5 +/- 8.8 in the omega-6 group (p = 0.048). In addition, the omega-3 group was superior to the omega-6 group with respect to change in severity of psoriasis per body area, change in overall erythema, overall scaling and overall infiltration, as well as change in overall assessment by the investigator and self-assessment by the patient. Response (defined as decrease in total PASI of at least 50% between admission and last value) was seen in 16 of 43 patients (37%) receiving the omega-3 emulsion and 9 of 40 patients (23%) receiving omega-6 fatty acid-based lipid emulsion. No serious side effects were observed. Within the first few days of omega-3 lipid administration, but not in the omega-6 supplemented patients, a manifold increase in plasma-free EPA concentration, neutrophil leukotriene B5 and platelet thromboxane B3 generation occurred.Intravenous omega-3-fatty acid administration is effective in the treatment of chronic plaque-type psoriasis. This effect may be related to changes in inflammatory eicosanoid generation.

This review paper describes our current perspective of autism spectrum disorders (ASD), taking into account past, current and future classification systems and the evolving definitions of ASD. International prevalence rates from 1965 to 2012 are presented and key issues, including whether there is an epidemic of autism and what this means in terms of thinking about possible causes of autism, are discussed. Also discussed is the need for high quality national data collection in Australia and the evidence, and lack of evidence, for the many theoretical causes of ASD. The lack of robust classification of autism along with limited high quality evidence base about its prevalence and possible causes leaves ample space for future discoveries.

Continuing from part 1, part 2 of the autism spectrum disorders review explores clinical practice and service delivery aspects of autism spectrum disorders including current assessment approaches in Australia, family-centred models of care, and key service structure and delivery issues. Treatments including behavioural interventions, established and emergent medication, and complementary and alternative therapies are discussed. The key role of paediatricians as both individual child and family care providers and advocates, as well as agents of service reform in Australia, is evident. Much still needs to be done.

Although personality disorder not otherwise specified (PDNOS) is highly prevalent and associated with a high burden of disease, only a few treatment studies in this patient group exist. This study is the first to investigate the effectiveness of different modalities of psychotherapy in patients with PDNOS, i.e., short-term (up to 6 months) and long-term (more than 6 months) outpatient, day hospital, and inpatient psychotherapy.A total of 205 patients with PDNOS were assigned to one of six treatment modalities. Effectiveness was assessed over 60 months after baseline. The primary outcome measure was symptom severity, and the secondary outcome measures included psychosocial functioning and quality of life. The study design was quasi-experimental, and the multiple propensity score was used to control for initial differences between treatment groups.All treatment modalities showed positive outcomes, especially in terms of improvements of symptom severity and social role functioning. At 12-month follow-up, after adjustment for initial differences between the treatment groups, short-term outpatient psychotherapy and short-term inpatient psychotherapy showed most improvement and generally outperformed the other modalities concerning symptom severity. At 60 months after baseline, effectiveness remained but observed differences between modalities mostly diminished.Patients with PDNOS benefit from psychotherapy both at short-term and long-term follow-up. Short-term outpatient psychotherapy and short-term inpatient psychotherapy seem to be superior to the other treatment modalities at 12-month follow-up. At 60-month follow-up, treatments showed mostly comparable effectiveness.The effectiveness of different modalities of psychotherapy in patients with PDNOS (i.e., short-term vs long-term; outpatient versus day hospital versus inpatient psychotherapy) has not yet been compared. Different modalities of psychotherapy are effective for patients with PDNOS, and positive effects remain after 5 years. In patients with PDNOS short-term (less than 6 months) outpatient psychotherapy and short-term inpatient psychotherapy seem to be superior to the four other treatment modalities at 12-month follow-up. At 60-month follow-up, treatments showed mostly comparable effectiveness.

Lenalidomide-rituximab therapy is effective in grade 1-2 follicular and mantle cell lymphoma, but its efficacy in diffuse large B-cell lymphoma (DLBCL), transformed large cell lymphoma (TL) and grade 3 follicular lymphoma (FLG3) is unknown. In this phase II trial, 45 patients with relapsed or refractory DLBCL (n=32), TL (n=9) or FLG3 (n=4) who had received 1-4 prior lines of treatment were given 20 mg oral lenalidomide on days 1-21 of each 28-day cycle, and intravenous rituximab (375 mg/m(2)) weekly during cycle 1. Grade 3/4 hematological toxicities included neutropenia (53%), lymphopenia (40%), thrombocytopenia (33%), leukopenia (27%) and anemia (18%), with a median follow-up time of 29.1 months (range 14.7-52.0 months). Overall response (OR) rate was 33%; median response duration was 10.2 months. Median progression-free survival (PFS) and overall survival (OS) were 3.7 and 10.7 months, respectively. Nine of the 15 responding patients (three partial response (PR), six complete response (CR)) proceeded with stem cell transplantation (SCT) and were censored at the time of transplantation. When data were analyzed without censoring, median PFS remained 3.7 months and response duration increased to 30.9 months. Rituximab plus oral lenalidomide is well tolerated and effective for patients with relapsed/refractory DLBCL and TL. SCT after lenalidomide-rituximab is associated with prolonged response duration.

Background: While psychopharmacological studies are common in patients with cluster A personality disorders, the effects of psychotherapy have received little attention. The aim of this study is to explore whether psychotherapeutic treatment yields health gains for these patients. Methods: The study was conducted between March 2003 and June 2008 in 6 mental health care centres in the Netherlands, with a sample of 57 patients with a DSM-IV-TR axis II cluster A diagnosis. Patients were assigned to 3 settings of psychotherapeutic treatment (outpatient, day hospital, inpatient), and effectiveness was assessed at 18 months after baseline. An intention-to-treat analysis was conducted for psychiatric symptoms (Brief Symptom Inventory), psychosocial functioning (Outcome Questionnaire-45) and quality of life (EQ-5D), using multilevel statistical modelling. As the study was non-randomised, the propensity score method was used to control for initial differences. Results: Patients in the day hospital and inpatient group improved substantially in terms of psychiatric symptoms, social and interpersonal functioning, and quality of life. Patients in the outpatient group showed less improvement. Direct comparison of the improvement of psychiatric symptoms showed significant results in favour of day hospital (p = 0.046) and inpatient (p = 0.01) treatment, as compared to outpatient treatment. However, due to substantial baseline differences, this direct comparison should be judged carefully. Conclusions: Cluster A psychopathology is not a contraindication to benefit from psychotherapy. This is especially true for more intensive forms like inpatient and day hospital treatment. Future research should focus more on psychotherapeutic treatment to gain further insight into effective treatment options for this patient group.

The current research examined whether people will attempt to modify internal aspects of the self to make them congruent with others, even when those modifications have negative implications for the self, a phenomenon we refer to as negative self-synchronization. We proposed that negative self-synchronization will occur only for individuals who are securely attached. Across 4 experiments, participants who were high in secure attachment were more likely than those low in attachment security to engage in negative self-synchronization (Experiments 1-4). Attachment style did not moderate positive self-synchronization (Experiments 1 and 2). In addition, priming secure attachment increased negative self-synchronization among insecure participants (Experiments 2 and 3). Conversely, priming insecure attachment decreased negative self-synchronization among secure participants (Experiment 4). Implications of these findings for social synchronization processes, the need to belong, and attachment security are discussed.

Background: For patients with cluster B personality disorders there is no consensus regarding the optimal treatment setting. The aim of this study was to compare the effectiveness of different psychotherapeutic settings for patients with cluster B personality disorders, i.e. outpatient, day hospital, and inpatient treatment. Methods: The study was conducted between March 2003 and June 2008 in 6 mental health care centres in the Netherlands, with a sample of 207 patients with a DSM-IV-TR axis II cluster B diagnosis. Patients were assigned to 3 different settings of psychotherapeutic treatment and effectiveness was assessed at 18 months after baseline. An intention-to-treat analysis was conducted for psychiatric symptoms (Brief Symptom Inventory), psychosocial functioning (Outcome Questionnaire-45), and quality of life (EQ-5D), using multilevel statistical modelling. As the study was non-randomised, the propensity score method was used to control for initial differences. Results: Patients in all 3 settings improved significantly in terms of psychiatric symptoms, social and interpersonal functioning, and quality of life 18 months after baseline. The inpatient group showed the largest improvements. The comparison of outpatient and inpatient treatment regarding psychiatric symptoms showed a marginally significant result (p = 0.057) in favour of inpatient treatment. Conclusions: Patients with cluster B personality disorders improved in all investigated treatment settings, with a trend towards larger improvements of psychiatric symptoms in the inpatient setting compared to the outpatient setting. Specialised inpatient treatment should be considered as a valuable treatment option for cluster B personality disorders, both in research and in clinical practice.

Randomized controlled trials are considered the best scientific proof of effectiveness. There is increasing concern, though, about their feasibility in psychotherapy research. We discuss a quasi-experimental study design for situations in which a randomized controlled trial is not feasible. Here, as an alternative strategy, the propensity score (PS) method is used to correct for selection bias.We used data from a Dutch research project, SCEPTRE (Study on Cost-Effectiveness of Personality Disorder Treatment). The sample consisted of 749 psychotherapy patients with personality pathology. We tested whether the PS method was useful and applicable. We examined differences between 2 treatment groups (short vs. long treatment duration) in pretreatment characteristics before and after PS correction. This revealed the impact of the PS on outcome differences.The PS offered statistical control over observed pretreatment differences between patients in a non-randomized study.When a randomized controlled trial is not possible, this quasi-experimental design using the PS could be a feasible alternative. Its advantages and limitations are discussed. Implemented carefully, this method is promising for future effectiveness research.

Objective:Despite scientific evidence of effectiveness, psychotherapy for personality disorders is not yet fully deployed, nor is its reimbursement self-evident. Both clinicians and health care policy-makers increasingly rely on evidence-based medicine and health economics when determining a treatment of choice and reimbursement. This article aims to contribute to that understanding by applying these criteria on psychotherapy as a treatment for patients with personality disorder.Method:We have evaluated the available empirical evidence on effectiveness and cost-effectiveness, and integrated this with necessity of treatment as a moderating factor.Results:The effectiveness of psychotherapy for personality disorders is well documented with favourable randomized trial results, 2 metaanalyses, and a Cochrane review. However, the evidence does not yet fully live up to modern standards of evidence-based medicine and is mostly limited to borderline and avoidant personality disorders. Data on cost-effectiveness suggest that psychotherapy for personality disorders may lead to cost-savings. However, state-of-the-art cost-effectiveness data are still scarce. An encouraging factor is that the available studies indicate that patients with personality disorder experience a high burden of disease, stressing the necessity of treatment.Conclusions:When applying an integrated vision on outcome, psychotherapy can be considered not only an effective treatment for patients with personality disorder but also most likely a cost-effective and necessary intervention. However, more state-of-the-art research is required before clinicians and health care policy-makers can fully appreciate the benefits of psychotherapy for personality disorders. Considerable progress is possible if researchers focus their efforts on evidence-based medicine and cost-effectiveness research.