Including Community Partners in the Development and Adaptation of Intervention Strategies to Prevent Initiation or Escalation of Opioid Misuse.

Current literature lacks clear examples of how to engage with communities in the development of opioid misuse interventions for diverse populations and across various settings. The National Institutes of Health (NIH) Helping to End Addiction Long-term® Initiative (HEAL) Prevention Cooperative (HPC) research projects work collaboratively with communities to develop and adapt their opioid misuse interventions to increase both feasibility and sustainability. Ten HPC projects were selected to receive NIH funding and are required to have partnerships with communities where their intervention is being conducted. This paper applies the Centers for Disease Control and Prevention (CDC)-adapted Public Participation Framework to examine the levels of community engagement used by each of these 10 HPC projects (Clinical and Translational Science Awards Consortium Community Engagement Key Function Committee Task Force on the Principles of Community Engagement, 2015). Using this framework, this paper illustrates the range of community engagement approaches and levels that the HPC projects rely on to develop, adapt, and adopt opioid prevention interventions across diverse populations and settings. This paper also lays a foundation for future examinations of the role of community engagement in intervention implementation and effectiveness and the level of community engagement that is necessary to improve intervention effectiveness.

Psychometric properties of EQ-5D-5L for use in patients with Graves' disease.

BACKGROUND: The EQ-5D-5 L is a commonly used generic measure of health. This study aimed to evaluate the psychometric properties of the EQ-5D-5 L in patients with Graves' disease (GD). METHODS: A prospective cohort of patients with GD recruited at three public hospitals in Hong Kong completed the EQ-5D-5 L and ThyPRO-39 questionnaires at baseline, 1-month, and 6-month follow-ups. Convergent validity was tested by examining the Spearman correlation between EQ-5D-5 L and ThyPRO-39 scores at baseline. 1-month test-retest reliability was assessed by Intraclass Correlation Coefficient (ICC), Gwet's Agreement Coefficient 2 (AC2), and percentage agreement. Responsiveness of EQ-5D-5 L index and EQ-VAS scores was assessed using effect size statistics (standardized effect size [SES] and standardized response mean [SRM]). RESULTS: Of 125 recruited patients, 101 (80.8%) and 100 (80.0%) patients were followed up at 1- and 6-month, respectively. For convergent validity, there was a moderate negative correlation between EQ-5D-5 L index or EQ-VAS score and ThyPRO-39 overall QoL-impact score (-0.350, -0.451), between EQ-VAS score and composite score (-0.483), and strong negative correlation between EQ-5D-5 L index score and composite score (-0.567). The Gwet's AC2 and percentage agreement were the highest in self-care (0.964 and 0.967), followed by mobility (0.952 and 0.962), usual activities (0.934 and 0.948), pain/discomfort (0.801 and 0.887), and anxiety/depression (0.788 and 0.882). The ICC for the EQ-5D-5 L index and the EQ-VAS was 0.707 and 0.700. For patients who reported having 'worsened' health at 6-month follow-up, the SES and SRM were - 0.66 and - 0.42 for EQ-5D-5 L index and - 1.15 and - 1.00 for EQ-VAS, respectively. CONCLUSIONS: The EQ-5D-5 L demonstrated convergent validity, test-retest reliability, and responsiveness to worsened health status among patients with GD.

CCX559 is a potent, orally-administered small molecule PD-L1 inhibitor that induces anti-tumor immunity.

The interaction of PD-L1 with PD-1 is a major immune checkpoint that limits effector T cell function against cancer cells; monoclonal antibodies that block this pathway have been approved in multiple tumor indications. As a next generation therapy, small molecule inhibitors of PD-L1 have inherent drug properties that may be advantageous for certain patient populations compared to antibody therapies. In this report we present the pharmacology of the orally-available, small molecule PD-L1 inhibitor CCX559 for cancer immunotherapy. CCX559 potently and selectively inhibited PD-L1 binding to PD-1 and CD80 in vitro, and increased activation of primary human T cells in a T cell receptor-dependent fashion. Oral administration of CCX559 demonstrated anti-tumor activity similar to an anti-human PD-L1 antibody in two murine tumor models. Treatment of cells with CCX559 induced PD-L1 dimer formation and internalization, which prevented interaction with PD-1. Cell surface PD-L1 expression recovered in MC38 tumors upon CCX559 clearance post dosing. In a cynomolgus monkey pharmacodynamic study, CCX559 increased plasma levels of soluble PD-L1. These results support the clinical development of CCX559 for solid tumors; CCX559 is currently in a Phase 1, first in patient, multicenter, open-label, dose-escalation study (ACTRN12621001342808).

Visualizing cell-cell communication using synthetic notch activated MRI.

Cell-cell communication plays a fundamental role in multicellular organisms. Cell-based cancer immunotherapies rely on the ability of innate or engineered receptors on immune cells to engage specific antigens on cancer cells to induce tumor kill. To improve the development and translation of these therapies, imaging tools capable of noninvasively and spatiotemporally visualizing immune-cancer cell interactions would be highly valuable. Using the synthetic Notch (SynNotch) system, we engineered T cells that upon interaction with a chosen antigen (CD19) on neighboring cancer cells induce the expression of optical reporter genes and the human-derived, magnetic resonance imaging (MRI) reporter gene organic anion transporting polypeptide 1B3 (OATP1B3). Administration of engineered T cells induced the antigen-dependent expression of all our reporter genes in mice bearing CD19-positive tumors but not CD19-negative tumors. Notably, due to the high spatial resolution and tomographic nature of MRI, contrast-enhanced foci within CD19-positive tumors representing OATP1B3-expressing T cells were clearly visible and their distribution was readily mapped. We then extended this technology onto human natural killer-92 (NK-92) cells, observing similar CD19-dependent reporter activity in tumor-bearing mice. Furthermore, we show that when delivered intravenously, engineered NK-92 cells can be detected via bioluminescence imaging in a systemic cancer model. With continued work, this highly modular imaging strategy could aid in the monitoring of cell therapies in patients and, beyond this, augment our understanding of how different cell populations interact within the body during normal physiology or disease.

Dual Magnetic Particle Imaging and Akaluc Bioluminescence Imaging for Tracking Cancer Cell Metastasis.

Magnetic particle imaging (MPI) provides hotspot tracking and direct quantification of superparamagnetic iron oxide nanoparticle (SPIO)-labelled cells. Bioluminescence imaging (BLI) with the luciferase reporter gene Akaluc can provide complementary information on cell viability. Thus, we explored combining these technologies to provide a more holistic view of cancer cell fate in mice. Akaluc-expressing 4T1Br5 cells were labelled with the SPIO Synomag-D and injected into the mammary fat pads (MFP) of four nude mice. BLI was performed on days 0, 6 and 13, and MPI was performed on days 1, 8 and 14. Ex vivo histology and fluorescence microscopy of MFP and a potential metastatic site was conducted. The BLI signal in the MFP increased significantly from day 0 to day 13 (p < 0.05), mirroring tumor growth. The MPI signal significantly decreased from day 1 to day 14 (p < 0.05) due to SPIO dilution in proliferating cells. Both modalities detected secondary metastases; however, they were visualized in different anatomical regions. Akaluc BLI complemented MPI cell tracking, allowing for longitudinal measures of cell viability and sensitive detection of distant metastases at different locations. We predict this multimodal imaging approach will help to evaluate novel therapeutics and give a better understanding of metastatic mechanisms.

Combined Shear Wave Elastography and EU TIRADS in Differentiating Malignant and Benign Thyroid Nodules.

Although multimodal ultrasound approaches have been suggested to potentially improve the diagnosis of thyroid cancer; the diagnostic utility of the combination of SWE and malignancy-risk stratification systems remains vague due to the lack of standardized criteria. The purpose of the study was to assess the diagnostic value of the combination of grey scale ultrasound assessment using EU TIRADS and shear wave elastography. 121 patients (126 nodules−81 benign; 45 malignant) underwent grey scale ultrasound and SWE imaging of nodules between 0.5 cm and 5 cm prior to biopsy and/or surgery. Nodules were analyzed based on size stratifications: <1 cm (n = 43); 1−2 cm (n = 52) and >2 cm (n = 31) and equivocal cytology status (n = 52), and diagnostic performance assessments were conducted. The combination of EU TIRADS with SWE using the SD parameter; maintained a high sensitivity and significantly improved the specificity of sole EU TIRADS for nodules 1−2 cm (SEN: 72.2% vs. 88.9%, p > 0.05; SPEC: 76.5% vs. 55.9%, p < 0.01) and >2 cm (SEN: 71.4% vs. 85.7%, p > 0.05; SPEC: 95.8% vs. 62.5%, p < 0.01). For cytologically-equivocal nodules; the combination with the SWE minimum parameter resulted in a significant reduction in sensitivity with increased specificity (SEN: 60% vs. 80%; SPEC: 83.4% vs. 37.8%; all p < 0.05). SWE in combination with EU TIRADS is diagnostically efficient in discriminating nodules > 1 cm but is not ideal for discriminating cytologically-equivocal nodules.

Diagnostic Value of AngioPLUS Microvascular Imaging in Thyroid Nodule Diagnosis Using Quantitative and Qualitative Vascularity Grading.

This study investigated the diagnostic value of the Angio Planewave Ultrasensitive (AngioPLUS) Doppler ultrasound in improving the efficacy of grey scale ultrasound in thyroid nodule diagnosis. The EU TIRADS was used for the grey scale ultrasound assessment of 94 thyroid nodules. conventional Doppler and AngioPLUS Doppler ultrasound images were evaluated using qualitative vascularity grading, where predominant central vascularity indicated malignancy-suspicion, and quantitative regional vascularity assessment, where predominant peripheral vascularity using a ratio vascularity index (RVI) of > 1 indicated benign disease. Diagnostic performance outcomes of sole and combination approaches were calculated based on final pathologic results. Using sole EU TIRADS and AngioPLUS + power Doppler imaging (APDI) based on qualitative vascularity and RVI, the results were a sensitivity of 83.3% vs. 83.3 vs. 66.7% and a specificity of 50% vs. 81.3% vs. 73.4, respectively. EU TIRADS combined with APDI significantly improved the specificity using both qualitative vascularity and RVI assessment approaches (84.4% and 81%, respectively, p < 0.05); and slightly reduced the sensitivity (76.7% and 58.1%). For cytologically-equivocal thyroid nodules, the combination approach using qualitative vascularity assessment outperformed the EU TIRADS (sensitivity: both were 88.9%; specificity: 77.4% vs. 38.7%, p < 0.05; and AUROC: 0.83 vs. 0.62, p < 0.05). APDI combined with EU TIRADS is diagnostically efficient in stratifying thyroid nodules, particularly cytologically-equivocal nodules.

Attaining biochemical euthyroidism early after total thyroidectomy in Graves' disease may lower long-term morbidity risk.

BACKGROUND: The relationship between good early control of thyroid hormone levels after thyroidectomy for Graves' disease (GD) and subsequent risks of mortality and morbidities is not well known. The aim of this study was to examine the association between thyroid hormone levels within a short interval after surgery and long-term mortality and morbidity risks from a population-based database. METHODS: Patients with GD who underwent complete/total thyroidectomy between 2006 and 2018 were selected from the Hong Kong Hospital Authority clinical management system. All patients were classified into three groups (euthyroidism, hypothyroidism, and hyperthyroidism) according to their thyroid hormone levels at 6, 12, and 24 months after surgery. Cox proportional hazards models were performed to compare the risks of all-cause mortality, cardiovascular disease (CVD), Graves' ophthalmopathy, and cancer. RESULTS: Over a median follow-up of 68 months with 5709 person-years, 949 patients were included for analysis (euthyroidism, n = 540; hypothyroidism, n = 282; and hyperthyroidism, n = 127). The hypothyroidism group had an increased risk of CVD (HR = 4.20, 95 per cent c.i. 2.37 to 7.44, P < 0.001) and the hyperthyroidism group had an increased risk of cancer (HR = 2.14, 95 per cent c.i. 1.55 to 2.97, P < 0.001) compared with the euthyroidism group. Compared with patients obtaining euthyroidism both at 6 months and 12 months, the risk of cancer increased in patients who achieved euthyroidism at 6 months but had an abnormal thyroid status at 12 months (HR = 2.33, 95 per cent c.i. 1.51 to 3.61, P < 0.001) and in those who had abnormal thyroid status at 6 months but achieved euthyroidism at 12 months (HR = 2.52, 95 per cent c.i. 1.60 to 3.97, P < 0.001). CONCLUSIONS: This study showed a higher risk of CVD in postsurgical hypothyroidism and a higher risk of cancer in hyperthyroidism compared with achieving euthyroidism early after thyroidectomy. Patients who were euthyroid at 6 months and 12 months had better outcomes than those achieving euthyroidism only at 6 months or 12 months. Attaining biochemical euthyroidism early after thyroidectomy should become a priority.

Long-term outcome of patients treated with antithyroid drugs, radioactive iodine or surgery for persistent or relapsed Graves' disease.

BACKGROUND: The aim of this study was to compare long-term mortality, morbidity, and cumulative healthcare costs between antithyroid drugs, radioactive iodine, and surgical treatment for patients with persistent or relapsed Graves' disease. METHODS: Data on patients with persistent or relapsed Graves' disease between 2006 and 2018 were retrieved from the Hong Kong Hospital Authority. Hazard ratios (HRs) estimated by Cox proportional hazards regression models were used to compare the risks of all-cause mortality, cardiovascular disease, atrial fibrillation, psychological disease, Graves' ophthalmopathy, and cancer across treatment groups. The 10-year healthcare cost and change in co-morbidity status were also estimated. RESULTS: Over a median follow-up of 79 months (22 636 person-years), a total of 3443 patients (antithyroid drug 2294, radioactive iodine 755, surgery 394) were analysed. Compared with antithyroid drug treatment, surgery was associated with significantly lower risks of all-cause mortality (HR 0.40, 95 per cent c.i. 0.36 to 0.45), cardiovascular disease (HR 0.54, 0.48 to 0.60), atrial fibrillation (HR 0.11, 0.09 to 0.14), psychological disease (HR 0.85, 0.79 to 0.92), Graves' ophthalmopathy (HR 0.09, 0.08 to 0.10), and cancer (HR 0.56, 0.50 to 0.63). Patients who underwent surgery also had a lower risk of all outcome events than those in the radioactive iodine group. The 10-year direct cumulative healthcare cost was €14 754 for surgery compared with €17 390 for antithyroid drugs, and €17 918 for the radioactive iodine group. CONCLUSION: Patients who underwent surgery for persistent or relapsed Graves' disease had lower risks of all-cause mortality and analysed morbidities. The 10-year cumulative healthcare cost in the surgery group was lowest among the three treatment alternatives.

Case report of congenital intestinal malrotation in an adult discovered three months status-post appendectomy.

INTRODUCTION AND IMPORTANCE: Intestinal malrotation is a congenital anomaly primarily diagnosed in children, with limited cases reported in adults. Prompt recognition is necessary to prevent life-threatening complications including bowel ischemia and death. We present a rare case of adult intestinal malrotation highlighting difficulty in diagnosis and surgical management. CASE PRESENTATION: A 37-year-old Caucasian woman presented with a 3-day history of worsening diffuse abdominal pain, three months status-post laparoscopic appendectomy. CT scan with contrast of the abdomen and pelvis demonstrated small bowel mesenteric swirling and descending duodenal transition point. Differential diagnosis included intestinal malrotation versus small bowel obstruction. Pre-operatively, the patient expressed frustration with years of abdominal pain and lack of improvement. Treatment with open surgical small bowel detorsion and ligation of the Ladd's bands was performed, after initial laparoscopic intervention was complicated by enterotomy. The patient recovered well post-operatively with final diagnosis of intestinal malrotation with midgut volvulus. Discharge home was delayed due to polysubstance withdrawal. Post-operatively, the patient reported immediate relief of symptoms which persisted at 2-week and 2-month follow-ups. CLINICAL DISCUSSION: Few reports of congenital malrotation diagnosed in adulthood are reported. This highlights the importance of evaluating all patients for malrotation when the appendix is found outside of the normal positioning in the RLQ, as surgical correction of malrotation is of utmost importance in such patients. CONCLUSION: Clinicians should consider intestinal malrotation in adults with recurrent vague abdominal symptoms. To our knowledge, this is the first report of congenital malrotation discovered in an adult after prior appendectomy.

Molecular Imaging Reveals a High Degree of Cross-Seeding of Spontaneous Metastases in a Novel Mouse Model of Synchronous Bilateral Breast Cancer.

PURPOSE: Synchronous bilateral breast cancer (SBBC) patients present with cancer in both breasts at the time of diagnosis or within a short time interval. They show higher rates of metastasis and lower overall survival compared to women with unilateral breast cancer. Here we established the first preclinical SBBC model and used molecular imaging to visualize the patterns of metastasis from each primary tumor. PROCEDURES: We engineered human breast cancer cells to express either Akaluc or Antares2 for bioluminescence imaging (BLI) and tdTomato or zsGreen for ex vivo fluorescence microscopy. Both cell populations were implanted into contralateral mammary fat pads of mice (n=10), and dual-BLI was performed weekly for up to day 29 (n=3), 38 (n=4), or 42 (n=3). Primary tumors and lungs were fixed, and ex vivo fluorescence microscopy was used to analyze the cellular makeup of micrometastases. RESULTS: Signal from both Antares2 and Akaluc was first detected in the lungs on day 28 and was present in 9 of 10 mice at endpoint. Ex vivo fluorescence microscopy of the lungs revealed that for mice sacrificed on day 38, a significant percentage of micrometastases were composed of cancer cells from both primary tumors (mean 37%; range 27 to 45%), while two mice sacrificed on day 42 showed percentages of 51% and 70%. CONCLUSIONS: A high degree of metastatic cross-seeding of cancer cells derived from bilateral tumors may contribute to faster metastatic growth and intratumoral heterogeneity. We posit that our work will help understand treatment resistance and optimal planning of SBBC treatment.

Comparative Analysis of Computer-Aided Diagnosis and Computer-Assisted Subjective Assessment in Thyroid Ultrasound.

The value of computer-aided diagnosis (CAD) and computer-assisted techniques equipped with different TIRADS remains ambiguous. Parallel diagnosis performances of computer-assisted subjective assessments and CAD were compared based on AACE, ATA, EU, and KSThR TIRADS. CAD software computed the diagnosis of 162 thyroid nodule sonograms. Two raters (R1 and R2) independently rated the sonographic features of the nodules using an online risk calculator while blinded to pathology results. Diagnostic efficiency measures were calculated based on the final pathology results. R1 had higher diagnostic performance outcomes than CAD with similarities between KSThR (SEN: 90.3% vs. 83.9%, p = 0.57; SPEC: 46% vs. 51%, p = 0.21; AUROC: 0.76 vs. 0.67, p = 0.02), and EU (SEN: 85.5% vs. 79%, p = 0.82; SPEC: 62% vs. 55%, p = 0.27; AUROC: 0.74 vs. 0.67, p = 0.06). Similarly, R2 had higher AUROC and specificity but lower sensitivity than CAD (KSThR-AUROC: 0.74 vs. 0.67, p = 0.13; SPEC: 61% vs. 46%, p = 0.02 and SEN: 75.8% vs. 83.9%, p = 0.31, and EU-AUROC: 0.69 vs. 0.67, p = 0.57, SPEC: 64% vs. 55%, p = 0.19, and SEN: 71% vs. 79%, p = 0.51, respectively). CAD had higher sensitivity but lower specificity than both R1 and R2 with AACE for 114 specified nodules (SEN: 92.5% vs. 88.7%, p = 0.50; 92.5% vs. 79.3%, p = 0.02, and SPEC: 26.2% vs. 54.1%, p = 0.001; 26.2% vs. 62.3%, p < 0.001, respectively). All diagnostic performance outcomes were comparable for ATA with 96 specified nodules. Computer-assisted subjective interpretation using KSThR is more ideal for ruling out papillary thyroid carcinomas than CAD. Future larger multi-center and multi-rater prospective studies with a diverse representation of thyroid cancers are necessary to validate these findings.

Brightening up Biology: Advances in Luciferase Systems for in Vivo Imaging.

Bioluminescence imaging (BLI) using luciferase reporters is an indispensable method for the noninvasive visualization of cell populations and biochemical events in living animals. BLI is widely performed with preclinical rodent models to understand disease processes and evaluate potential cell- or gene-based therapies. However, in vivo BLI remains constrained by low photon production and tissue attenuation, limiting the sensitivity of reporting from small numbers of cells in deep locations and hindering its application to larger animal models. This Review highlights recent advances in the development of luciferase systems that improve the sensitivity of in vivo BLI and discusses the expanding array of biological applications.

A Mobile Health Breast Cancer Educational and Screening Intervention Tailored for Low-Income, Uninsured Latina Immigrants.

Objective: To investigate the efficacy of mobile health (mHealth) intervention strategies that delivered either personalized, culturally, and linguistically tailored cell phone voice messages or text messages related to breast cancer and prevention, compared to the control group, to determine which strategy is more likely to increase breast cancer knowledge and screening mammography among low-income Latina immigrants. Methods: This randomized controlled trial assigned 256 Latina immigrants 40 years of age or older to one of three groups: an automated cell phone voice message group, an automated text message group, or the control group (mail). The mHealth intervention employed a comprehensive approach that included breast cancer and prevention education and free mammography screening. Outcome measures included knowledge of breast cancer and breast cancer prevention, and adherence to screening mammography. Results: There was a general increase in breast cancer knowledge after the educational intervention for all the groups [p = 0.01, t(199) = 3.996]. Knowledge increase and mammography adherence did not differ based on group. Conclusion: More important than the actual method of communication is how breast cancer and prevention messages are constructed, who the messenger is, and the enabling factors that facilitate screening adherence. A breast cancer preventive intervention program that is personalized, culturally and linguistically tailored, and offers a free or low-cost mammogram holds promise to be an effective method in reaching an underserved Latina population with a high breast cancer burden.

A prospective 5-year study on the use of transient elastography to monitor the improvement of non-alcoholic fatty liver disease following bariatric surgery.

Liver stiffness measurement (LSM) by transient elastography (TE) is a non-invasive assessment for diagnosing and staging liver fibrosis in non-alcoholic fatty liver disease (NAFLD). Evidence on its role as a longitudinal monitoring tool is lacking. This study aims to evaluate the role of TE in monitoring NAFLD improvement following bariatric surgery. This study prospectively recruited 101 morbidly obese patients undergoing laparoscopic bariatric surgery for intraoperative liver biopsy. Thirty-seven patients of the cohort received perioperative TE. Postoperative anthropometric, biochemical and LSM data were collected annually for 5 years. In 101 patients receiving liver biopsy (mean age 40.0 ± 10.3 years, mean body-mass-index (BMI) 40.0 ± 5.7 kg/m2), NASH and liver fibrosis were diagnosed in 42 (41.6%) and 48 (47.5%) patients respectively. There were 29 (28.7%) stage 1, 11 (10.9%) stage 2, 7 (6.9%) stage 3, and 1 (1.0%) stage 4 fibrosis. In 37 patients receiving TE (mean age 38.9 ± 10.8 years, mean BMI 41.1 ± 5.6 kg/m2), the percentages of total weight loss were 21.1 ± 7.6% at 1 year, 19.7 ± 8.3% at 3 years, and 17.1 ± 7.0% at 5 years after surgery. The mean LSM reduced significantly from 9.8 ± 4.6 kPa at baseline to 6.9 ± 3.4 kPa at 1 year, 7.3 ± 3.0 kPa at 3 years, and 6.8 ± 2.6 kPa at 5 years (P = 0.002). Using pre-defined LSM cut-offs, the rates of significant fibrosis, advanced fibrosis and cirrhosis being ruled out at 5 years improved from baseline values of 43.7 to 87.5% (P < 0.001), 56.8 to 91.7% (P < 0.001), and 64.9 to 91.7% (P < 0.001), respectively. TE was a useful monitoring tool in demonstrating the improvement of liver fibrosis following bariatric surgery.

Diagnostic performance evaluation of different TI-RADS using ultrasound computer-aided diagnosis of thyroid nodules: An experience with adjusted settings.

BACKGROUND: Thyroid cancer diagnosis has evolved to include computer-aided diagnosis (CAD) approaches to overcome the limitations of human ultrasound feature assessment. This study aimed to evaluate the diagnostic performance of a CAD system in thyroid nodule differentiation using varied settings. METHODS: Ultrasound images of 205 thyroid nodules from 198 patients were analysed in this retrospective study. AmCAD-UT software was used at default settings and 3 adjusted settings to diagnose the nodules. Six risk-stratification systems in the software were used to classify the thyroid nodules: The American Thyroid Association (ATA), American College of Radiology Thyroid Imaging, Reporting, and Data System (ACR-TIRADS), British Thyroid Association (BTA), European Union (EU-TIRADS), Kwak (2011) and the Korean Society of Thyroid Radiology (KSThR). The diagnostic performance of CAD was determined relative to the histopathology and/or cytology diagnosis of each nodule. RESULTS: At the default setting, EU-TIRADS yielded the highest sensitivity, 82.6% and lowest specificity, 42.1% while the ATA-TIRADS yielded the highest specificity, 66.4%. Kwak had the highest AUROC (0.74) which was comparable to that of ACR, ATA, and KSThR TIRADS (0.72, 0.73, and 0.70 respectively). At a hyperechoic foci setting of 3.5 with other settings at median values; ATA had the best-balanced sensitivity, specificity and good AUROC (70.4%; 67.3% and 0.71 respectively). CONCLUSION: The default setting achieved the best diagnostic performance with all TIRADS and was best for maximizing the sensitivity of EU-TIRADS. Adjusting the settings by only reducing the sensitivity to echogenic foci may be most helpful for improving specificity with minimal change in sensitivity.

The effect of bariatric surgery on the improvement of lower urinary tract symptoms in morbidly obese male patients.

BACKGROUND: Lower urinary tract symptoms (LUTS) are strongly linked with obesity. Whether bariatric surgery can effectively alleviate LUTS in morbidly obese men is unknown. The objective of the present study was to evaluate the effectiveness of bariatric surgery in reducing the prevalence and severity of male LUTS in obese patients. METHODS: This was a prospective observational study on consecutive morbidly obese men undergoing bariatric surgery. The International Prostate Symptom Score (IPSS) was used to assess for LUTS before and at 1-3 years after surgery. The 3-year changes in IPSS, the changes in LUTS severity, and the factors associated with LUTS improvement were evaluated. RESULTS: This study recruited 143 morbidly obese men (mean age 43.0 ± 10.4 years) undergoing sleeve gastrectomy (n = 89) and Roux-en-Y gastric bypass (n = 54). The rates of follow-up after surgery were 94.4% (n = 119/126) at 1 year, 90.6% (n = 96/106) at 2 years, and 81.2% (n = 69/85) at 3 years. After surgery, there was significant body mass index reduction from 39.1 ± 5.2 kg/m2 preoperatively to 30.1 ± 4.8 kg/m2 at 1 year and 31.5 ± 4.9 kg/m2 at 3 years (P < 0.001). There was significant reduction in IPSS total symptom score, quality of life score, frequency score, and nocturia score (P < 0.05). The prevalence of moderate to severe LUTS reduced from 35.0% (29.4% moderate; 5.6% severe) preoperatively to 21.8% (19.3% moderate; 2.5% severe) at 1 year and 30.4% (24.6% moderate; 5.8% severe) at 3 years (P < 0.001). LUTS improvement was significantly associated with body fat percentage reduction (P = 0.012) and was not associated with weight loss or improvement of metabolic parameters. CONCLUSIONS: Bariatric surgery was an effective and durable intervention for alleviating the prevalence and severity of LUTS in morbidly obese men for up to 3 years.

Artery to vein configuration of arteriovenous fistula improves hemodynamics to increase maturation and patency.

Arteriovenous fistulae (AVF) are the preferred mode of hemodialysis access, but 60% of conventional [vein-to-artery (V-A)] AVF fail to mature, and only 50% remain patent at 1 year. We previously showed improved maturation and patency in a pilot study of the radial artery deviation and reimplantation (RADAR) technique that uses an artery-to-vein (A-V) configuration. Here, we show that RADAR exhibits higher rates of maturation, as well as increased primary and secondary long-term patencies. RADAR is also protective in female patients, where it is associated with decreased reintervention rates and improved secondary patency. RADAR and conventional geometries were compared further in a rat bilateral carotid artery-internal jugular vein fistula model. There was decreased cell proliferation and neointimal hyperplasia in the A-V configuration in male and female animals, but no difference in hypoxia between the A-V and V-A configurations. Similar trends were seen in uremic male rats. The A-V configuration also associated with increased peak systolic velocity and expression of Kruppel-like factor 2 and phosphorylated endothelial nitric oxide synthase, consistent with improved hemodynamics. Computed tomography and ultrasound-informed computational modeling showed different hemodynamics in the A-V and V-A configurations, and improving the hemodynamics in the V-A configuration was protective against neointimal hyperplasia. These findings collectively demonstrate that RADAR is a durable surgical option for patients requiring radial-cephalic AVF for hemodialysis access.

Author Correction: Inhibition of the Akt1-mTORC1 Axis Alters Venous Remodeling to Improve Arteriovenous Fistula Patency.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.