Analysis of Host Responses to Hepatitis B and Delta Viral Infections in a Micro-scalable Hepatic Co-culture System.

Hepatitis B virus (HBV) remains a major global health problem with 257 million chronically infected individuals worldwide, of whom approximately 20 million are co-infected with hepatitis delta virus (HDV). Progress toward a better understanding of the complex interplay between these two viruses and the development of novel therapies have been hampered by the scarcity of suitable cell culture models that mimic the natural environment of the liver. Here, we established HBV and HBV/HDV co-infections and super-infections in self-assembling co-cultured primary human hepatocytes (SACC-PHHs) for up to 28 days in a 384-well format and highlight the suitability of this platform for high-throughput drug testing. We performed RNA sequencing at days 8 and 28 on SACC-PHHs, either HBV mono-infected or HBV/HDV co-infected. Our transcriptomic analysis demonstrates that hepatocytes in SACC-PHHs maintain a mature hepatic phenotype over time, regardless of infection condition. We confirm that HBV is a stealth virus, as it does not induce a strong innate immune response; rather, oxidative phosphorylation and extracellular matrix-receptor interactions are dysregulated to create an environment that promotes persistence. Notably, HDV co-infection also did not lead to statistically significant transcriptional changes across multiple donors and replicates. The lack of innate immune activation is not due to SACC-PHHs being impaired in their ability to induce interferon stimulated genes (ISGs). Rather, polyinosinic:polycytidylic acid exposure activates ISGs, and this stimulation significantly inhibits HBV infection, yet only minimally affects the ability of HDV to infect and persist. Conclusion: These data demonstrate that the SACC-PHH system is a versatile platform for studying HBV/HDV co-infections and holds promise for performing chemical library screens and improving our understanding of the host response to such infections.

A novel method for predicting superior gluteal nerve safe zones in the lateral approach to the hip.

INTRODUCTION: The superior gluteal nerve (SGN) is at risk for laceration during lateral approach total hip arthroplasty (THA). The purpose of this study is to assess the accuracy of the trochanter-to-iliac crest distance (TCD) and the nerve-to-trochanter distance (NTD) ratio in determining a reproducible safe zone around the SGN independent of height. MATERIALS AND METHODS: Eighteen hemipelvises were dissected and the SGNs were exposed. The distance (NTD) from greater trochanter (GT) to the most inferior branch of the SGN encountered in each of the three approaches (Bauer et al., 1979) was measured. A reference distance (TCD) was measured from the GT to the highest point on the iliac crest. The NTD was divided by the TCD to generate standardized ratios. Coefficient of variation CV = (SD/mean) × 100 was calculated for each distance and ratio to measure relative variability. RESULTS: The standardized ratios (and CV) were determined for the nerve branches in three different surgical approaches: Hardinge 0.464 (0.9%), Bauer 0.406 (1.7%), and Frndak 0.338 (4.1%). There was a strong correlation of the individual NTDs with the TCD: NTD for Hardinge (r = 0.996, p < .001), NTD for Bauer (r = 0.984, p < .001), and NTD for Frndak (r = 0.932, p < .001). CONCLUSION: By measuring the TCD preoperatively and using the respective standardized ratios, surgeons can accurately predict the NTD and how proximal to the GT each SGN branch can be expected to be encountered during lateral approach to the hip. This will allow surgeons to work with a more precise safe zone around the SGN and minimize the possibility for a nerve injury.

Superior Capsule Reconstruction With Subacromial Allograft Spacer: Biomechanical Cadaveric Study of Subacromial Contact Pressure and Superior Humeral Head Translation.

PURPOSE: To investigate the biomechanical effects of superior capsule reconstruction with subacromial allograft spacer on superior humeral head translation and subacromial contact pressure. METHODS: Eight cadaveric shoulder specimens were tested in 4 conditions: (1) intact rotator cuff, (2) supraspinatus tear and superior capsule excision, (3) superior capsule reconstruction with human dermal allograft, and (4) superior capsule reconstruction with subacromial resurfacing using human dermal allograft. In each condition, specimens were tested at 0, 30, 60, and 90° of shoulder abduction in balanced and unbalanced loaded states for subacromial contact pressure and superior humeral head translation. Statistical comparisons were made using a repeated-measures analysis of variance test, followed by a Tukey post hoc test for pairwise comparisons. A P value <.05 was set as statistically significant. RESULTS: Superior humeral head translation and subacromial contact pressure were increased after irreparable rotator cuff tear (P = .001). There was no significant difference between superior capsule reconstruction and intact cuff in regard to superior humeral head translation and subacromial contact pressure at all abduction angles. Superior capsule reconstruction with subacromial resurfacing decreased superior humeral head translation relative to intact (0°, P = .004; 30°, P = .02; 60°, P = .08; 90°, P = .01), superior capsule reconstruction (0°, P = .001; 30°, P = .003; 60°, P = .019; 90°, P = .001), and cuff-deficient states (P = .001). Superior capsule reconstruction with subacromial resurfacing resulted in nonsignificant increases in subacromial contact pressure relative to intact cuff at 0 to 90° abduction angles. CONCLUSIONS: Superior capsule reconstruction with subacromial resurfacing using human dermal allograft results in decreased superior humeral head translation relative to superior capsule reconstruction with human dermal allograft only, while increasing subacromial contact pressure. CLINICAL RELEVANCE: Superior capsule reconstruction with subacromial resurfacing using human dermal allograft reduces superior humeral head translation while increasing subacromial contact pressure in a cadaveric model.

Osseous Rosai-Dorfman Disease Presenting as a Solitary Lesion of the Distal Radius.

Rosai-Dorfman disease, also known as sinus histiocytosis with massive lymphadenopathy, is a rare entity in which bone involvement occurs in less than 5% to 10% of patients and skeletal cases are usually multifocal. Extranodal solitary lesions of bone without nodal involvement or additional clinical manifestations are exceedingly rare. We present the clinical course and management of a 34-year-old African American woman who presented with the disease as a solitary lesion of the distal radius.

In Hospital Outcomes of Total Hip Arthroplasty in the Medicaid Population.

Total hip arthroplasty (THA) is one of the most common orthopaedic procedures. This study's purpose was to evaluate national trends, patient demographics and hospital outcomes for Medicaid patients who underwent a primary THA. The National Hospital Discharge Survey (NHDS) database was queried for patients undergoing THA from 2001-2010. Patients were stratified into two groups based on insurance. We found from 2001-2005, Medicaid accounted for 2.38% of all THA performed, increasing insignificantly to 2.61% between 2006-2010. The Medicaid group was younger (50.3 vs. 65.6 years, p < 0.01). Length of stay was longer for the Medicaid group (4.6 vs. 4.0 days, p < 0.01). Medicaid patients were more likely to be discharged home (53.7% vs. 47.2%, p < 0.01) and less likely to be discharged to rehabilitation facilities (24.4% vs. 29.0%, p < 0.05). In conclusion, we discovered that the rate of Medicaid insurance in patients undergoing primary THA was stable through 2010, prior to the Affordable Care Act. We found Medicaid THA patients had longer length of stay, despite being a mean 15 years younger than the non-Medicaid cohort. Medicaid insurance status should be factored into risk adjustment models to avoid creating additional disincentive to treat the Medicaid population. (Journal of Surgical Orthopaedic Advances 28(4):281-284, 2019).

Location of the Popliteal Artery in Knee Extension on Magnetic Resonance Imaging.

The goal of this study was to define the course of the popliteal artery (PA) and determine any variability among different patient demographics; by identifying risk factors for injury, surgeons can decrease patient morbidity and mortality. Ninety-four adult magnetic resonance imaging studies of the knee were reviewed. In extension, the artery is at most 7.87 mm posterior and 4.83 mm lateral to the midline below the tibial plateau. Proximally, the artery is more anterior and midline. With increasing body mass indexes, the artery is more posterior at any level. At the femur, 1 cm above the distal articular surface, the artery was more posterior in younger patients; 1 cm below the joint line, it was more posterior in elder patients. Attention should be given during total knee arthroplasty, revision surgery, lateral meniscal repair, posterior cruciate ligament reconstruction, high tibial osteotomy, and fixation of tibial tubercle fractures. Proximally, the PA is more anterior and midline, placing it at significant risk during these procedures. (Journal of Surgical Orthopaedic Advances 27(4):325-328, 2018).

Long-enduring primary hepatocyte-based co-cultures improve prediction of hepatotoxicity.

The failure of drug candidates during clinical trials and post-marketing withdrawal due to Drug Induced Liver Injury (DILI), results in significant late-stage attrition in the pharmaceutical industry. Animal studies have proven insufficient to definitively predict DILI in the clinic, therefore a variety of in vitro models are being tested in an effort to improve prediction of human hepatotoxicity. The model system described here consists of cryopreserved primary rat, dog or human hepatocytes co-cultured together with a fibroblast cell line, which aids in the hepatocytes' maintenance of more in vivo-like characteristics compared to traditional hepatic mono-cultures, including long term viability and retention of activity of cytochrome P450 isozymes. Cell viability was assessed by measurement of ATP following treatment with 29 compounds having known hepatotoxic liabilities. Hµrelrat™, Hµreldog™, and Hµrelhuman™ hepatic co-cultures were treated for 24h, or under repeat-dosing for 7 or 13days, and compared to rat and human hepatic mono-cultures following single-dose exposure for 24h. The results allowed for a comparison of cytotoxicity, species-specific responses and the effect of repeat compound exposure on the prediction of hepatotoxic potential in each model. Results show that the co-culture model had greater sensitivity compared to that of the hepatic mono-cultures. In addition, "time-based ratios" were determined by dividing the compounds' 24-hour TC50/Cmax values by TC50/Cmax values measured after dosing for either 7 or 13days. The results suggest that this approach may serve as a useful adjunct to traditional measurements of hepatotoxicity, improving the predictive value of early screening studies.

Predictivity of dog co-culture model, primary human hepatocytes and HepG2 cells for the detection of hepatotoxic drugs in humans.

Drug induced liver injury (DILI) is a major cause of attrition during early and late stage drug development. Consequently, there is a need to develop better in vitro primary hepatocyte models from different species for predicting hepatotoxicity in both animals and humans early in drug development. Dog is often chosen as the non-rodent species for toxicology studies. Unfortunately, dog in vitro models allowing long term cultures are not available. The objective of the present manuscript is to describe the development of a co-culture dog model for predicting hepatotoxic drugs in humans and to compare the predictivity of the canine model along with primary human hepatocytes and HepG2 cells. After rigorous optimization, the dog co-culture model displayed metabolic capacities that were maintained up to 2 weeks which indicates that such model could be also used for long term metabolism studies. Most of the human hepatotoxic drugs were detected with a sensitivity of approximately 80% (n=40) for the three cellular models. Nevertheless, the specificity was low approximately 40% for the HepG2 cells and hepatocytes compared to 72.7% for the canine model (n=11). Furthermore, the dog co-culture model showed a higher superiority for the classification of 5 pairs of close structural analogs with different DILI concerns in comparison to both human cellular models. Finally, the reproducibility of the canine system was also satisfactory with a coefficient of correlation of 75.2% (n=14). Overall, the present manuscript indicates that the dog co-culture model may represent a relevant tool to perform chronic hepatotoxicity and metabolism studies.

Dabigatran versus warfarin in patients with atrial fibrillation: an analysis of patients undergoing cardioversion.

BACKGROUND: The Randomized Evaluation of Long-Term Anticoagulation Therapy (RE-LY) trial compared dabigatran 110 mg BID (D110) and 150 mg BID (D150) with warfarin for stroke prevention in 18 113 patients with nonvalvular atrial fibrillation. METHODS AND RESULTS: Cardioversion on randomized treatment was permitted. Precardioversion transesophageal echocardiography was encouraged, particularly in dabigatran-assigned patients. Data from before, during, and 30 days after cardioversion were analyzed. A total of 1983 cardioversions were performed in 1270 patients: 647, 672, and 664 in the D110, D150, and warfarin groups, respectively. For D110, D150, and warfarin, transesophageal echocardiography was performed before 25.5%, 24.1%, and 13.3% of cardioversions, of which 1.8%, 1.2%, and 1.1% were positive for left atrial thrombi. Continuous treatment with study drug for ≥3 weeks before cardioversion was lower in D110 (76.4%) and D150 (79.2%) compared with warfarin (85.5%; P<0.01 for both). Stroke and systemic embolism rates at 30 days were 0.8%, 0.3%, and 0.6% (D110 versus warfarin, P=0.71; D150 versus warfarin, P=0.40) and similar in patients with and without transesophageal echocardiography. Major bleeding rates were 1.7%, 0.6%, and 0.6% (D110 versus warfarin, P=0.06; D150 versus warfarin, P=0.99). CONCLUSIONS: This study is the largest cardioversion experience to date and the first to evaluate a novel anticoagulant in this setting. The frequencies of stroke and major bleeding within 30 days of cardioversion on the 2 doses of dabigatran were low and comparable to those on warfarin with or without transesophageal echocardiography guidance. Dabigatran is a reasonable alternative to warfarin in patients requiring cardioversion.

Dabigatran versus warfarin in patients with atrial fibrillation.

BACKGROUND: Warfarin reduces the risk of stroke in patients with atrial fibrillation but increases the risk of hemorrhage and is difficult to use. Dabigatran is a new oral direct thrombin inhibitor. METHODS: In this noninferiority trial, we randomly assigned 18,113 patients who had atrial fibrillation and a risk of stroke to receive, in a blinded fashion, fixed doses of dabigatran--110 mg or 150 mg twice daily--or, in an unblinded fashion, adjusted-dose warfarin. The median duration of the follow-up period was 2.0 years. The primary outcome was stroke or systemic embolism. RESULTS: Rates of the primary outcome were 1.69% per year in the warfarin group, as compared with 1.53% per year in the group that received 110 mg of dabigatran (relative risk with dabigatran, 0.91; 95% confidence interval [CI], 0.74 to 1.11; P<0.001 for noninferiority) and 1.11% per year in the group that received 150 mg of dabigatran (relative risk, 0.66; 95% CI, 0.53 to 0.82; P<0.001 for superiority). The rate of major bleeding was 3.36% per year in the warfarin group, as compared with 2.71% per year in the group receiving 110 mg of dabigatran (P=0.003) and 3.11% per year in the group receiving 150 mg of dabigatran (P=0.31). The rate of hemorrhagic stroke was 0.38% per year in the warfarin group, as compared with 0.12% per year with 110 mg of dabigatran (P<0.001) and 0.10% per year with 150 mg of dabigatran (P<0.001). The mortality rate was 4.13% per year in the warfarin group, as compared with 3.75% per year with 110 mg of dabigatran (P=0.13) and 3.64% per year with 150 mg of dabigatran (P=0.051). CONCLUSIONS: In patients with atrial fibrillation, dabigatran given at a dose of 110 mg was associated with rates of stroke and systemic embolism that were similar to those associated with warfarin, as well as lower rates of major hemorrhage. Dabigatran administered at a dose of 150 mg, as compared with warfarin, was associated with lower rates of stroke and systemic embolism but similar rates of major hemorrhage. (ClinicalTrials.gov number, NCT00262600.)

Patient Utilization of Online Information and its Influence on Orthopedic Surgeon Selection: Cross-sectional Survey of Patient Beliefs and Behaviors.

BACKGROUND: Patient attitudes and behavior are critical to understand owing to the increasing role of patient choice. There is a paucity of investigation into the perceived credibility of online information and whether such information impacts how patients choose their surgeons. OBJECTIVE: The purpose of this study was to explore the attitudes and behavior of patients regarding online information and orthopedic surgeon selection. Secondary purposes included gaining insight into the relative importance of provider selection factors, and their association with patient age and education level. METHODS: This was a cross-sectional study involving five multispecialty orthopedic surgery groups. A total of 329 patients who sought treatment by six different orthopedic surgeons were asked to anonymously answer a questionnaire consisting of 25 questions. Four questions regarded demographic information, 10 questions asked patients to rate the importance of specific criteria regarding the selection of their orthopedic surgeon (on a 4-point Likert scale), and 6 questions were designed to determine patient attitude and behaviors related to online information. RESULTS: Patient-reported referral sources included the emergency room (29/329, 8.8%), friend (42/329, 12.8%), insurance company (47/329, 14.3%), internet search/website (28/329, 8.5%), primary care physician (148/329, 45.0%), and other (34/329, 10.3%). Among the 329 patients, 130 (39.5%) reported that they searched the internet for information before their first visit. There was a trend of increased belief in online information to be accurate and complete in younger age groups (P=.02). There was an increased relative frequency in younger groups to perceive physician rating websites to be unbiased (P=.003), provide sufficient patient satisfaction information (P=.01), and information about physician education and training (P=.03). There was a significant trend for patients that found a surgeon's website to be useful (P<.001), with the relative frequency increased in younger age groups. CONCLUSIONS: This study shows that insurance network, physician referrals, appointment availability, and office location are important to patients, whereas advertising and internet reviews by other patients were considered to be not as helpful in choosing an orthopedic surgeon. Future studies may seek to identify obstacles to patients in integrating online resources for decision-making and strategies to improve health-seeking behaviors.

Dabigatran and warfarin in vitamin K antagonist-naive and -experienced cohorts with atrial fibrillation.

BACKGROUND: The comparison of anticoagulants dabigatran and warfarin might be most equitable in vitamin K antagonist (VKA)-naive patients. METHODS AND RESULTS: Warfarin and 2 doses of dabigatran-110 mg BID (D110) and 150 mg BID (D150)-were compared in a balanced population of VKA-naive (≤62 days of lifetime VKA exposure, with 33% never prescribed a VKA) and VKA-experienced patients with atrial fibrillation (n=18 113). For VKA-naive and -experienced patients assigned warfarin, the time in therapeutic range (international normalized ratio 2.0 to 3.0) was 62% and 67%, respectively, and 61% and 66% for those never and ever prescribed a VKA. In VKA-naive patients, stroke and systemic embolism rates were 1.57%, 1.07%, and 1.69% per year for D110, D150, and warfarin, respectively. D110 was similar to warfarin (P=0.65); D150 was superior (P=0.005). Major bleeding rates were 3.11%, 3.34%, and 3.57% per year, respectively. D110 and D150 were similar to warfarin (P=0.19 and P=0.55). Intracranial bleeding rates were 0.19%, 0.33%, and 0.73% per year, respectively. D110 and D150 were lower than warfarin (P<0.001 and P=0.005). In VKA-experienced patients, stroke and systemic embolism rates were 1.51%, 1.15%, and 1.74% per year for D110, D150, and warfarin, respectively. D110 was similar to warfarin (P=0.32); D150 was superior (P=0.007). Major bleeding rates were 2.66%, 3.30%, and 3.57% per year, respectively. D110 was lower than warfarin (P=0.003); D150 was similar (P=0.41). Intracranial bleeding rates were 0.26%, 0.32%, and 0.79% per year, respectively. D110 and D150 were lower than warfarin (P<0.001 for both). Results were similar for patients never on a VKA. CONCLUSIONS: Previous VKA exposure does not influence the benefits of dabigatran at either dose compared with warfarin. CLINICAL TRIAL REGISTRATION: http://www.clinicaltrials.gov. Unique identifier: NCT00262600.

Unusual cause of gas complicating a biloma, postcholecystectomy.

A 50-year-old man presented to the emergency department with abdominal pain, vomiting and fever. He had been admitted 6 months ago with acute cholecystitis when he underwent endoscopic retrograde cholangiopancreatography (ERCP) to remove ductal gallstones. Elective cholecystectomy was performed 3 days prior to the current admission. CT demonstrated a fluid and gas containing collection in the gallbladder fossa, biliary gas and free intra-abdominal gas. ERCP revealed a retained common bile duct gallstone and leakage from the cystic duct remnant. We postulate that the gas within the collection originated from intrahepatic gas post-ERCP or from a gas forming organism. The free intra-abdominal gas originated from the collection rather than an intraoperative bowel injury. This complicated case highlights an unusual appearance of a common complication. It demonstrates the importance of discussion with the clinical team to ensure that an accurate diagnosis is made and the correct treatment is provided.

Pullout Strength After Multiple Reinsertions in Radial Bone Fixation.

Background: Due to bone cutting loss from self-tapping screws (STS), progressive destruction of bone can occur with each reinsertion during surgery. When considering the use of jigs that utilize multiple insertions such as those seen in ulnar and radial shortening osteotomy systems, or scenarios where a screw needs to be removed and reinserted due to some technical issue, this can be concerning, as multiple studies examining the effects of multiple reinsertions and the relationship between insertional torque and pullout strength have had mixed results. Methods: Insertional torque and pullout strength were experimentally measured following multiple reinsertions of STS for up to 5 total insertions for various densities and locations along radial sawbone shafts. Results: Torque and pullout strength were significantly greater in middle segments of the radial shaft. Our trials corroborate previous literature regarding a significant reduction in fixation between 1 and 2 insertions; beyond this, there was no significant difference between pullout strength across all segment locations as well as bone densities for 3 to 5 insertions. There was a moderate to high correlation of insertional torque to pullout strength noted across all bone densities and segments (Pearson r = 0.663, P < .001). Conclusion: While reinsertion of STS between 1 and 2 insertions has been shown to significantly differ in pullout strength, beyond this, there does not appear to be a significant difference in up to 5 insertions at any specific region of radial bone across a range of sawbone densities. Further insertions may be considered with caution.

Rationale and design of RE-LY: randomized evaluation of long-term anticoagulant therapy, warfarin, compared with dabigatran.

Vitamin K antagonists (VKAs) are effective for stroke prevention in patients with atrial fibrillation (AF) but are difficult to use. Dabigatran etexilate is a prodrug that is rapidly converted to the active direct thrombin inhibitor dabigatran. It is administered in a fixed dose without laboratory monitoring and is being compared with warfarin (international normalized ratio 2-3) in the RE-LY trial. Two doses of dabigatran (110 and 150 mg BID) are being evaluated. RE-LY is a phase 3, prospective, randomized, open-label multinational (44 countries) trial of patients with nonvalvular AF and at least 1 risk factor for stroke. Recruitment concluded with a total of 18,113 patients. Patients who were VKA-naive and experienced are included in balanced proportions. The primary outcome is stroke (including hemorrhagic) or systemic embolism. Safety outcomes are bleeding, liver function abnormalities, and other adverse events. Adjudication of end points is blinded to drug assignment. The trial is expected to accrue a minimum of 450 events with a minimum 1-year of follow-up. RE-LY is the largest AF stroke prevention trial yet undertaken. It is unique because it includes equal numbers of VKA-experienced and naive patients and evaluates 2 different dosages of dabigatran, which may allow tailoring of dosing to individual patient needs. The worldwide site distribution and broad range of stroke risk further increase the general applicability of the trial. Results are expected in 2009.

Allograft Tendon Interposition Arthroplasty of the Hallux Metatarsophalangeal Joint: A Technique Guide and Literature Review.

The "anchovy" interpositional arthroplasty technique can be used as a salvage option for failed hallux rigidus procedures. The operative technique utilized by the senior author is described. Careful soft-tissue handling, meticulous joint space and graft preparation, and interposition graft stabilization using a bone tunnel and suture anchors are unique aspects of this technique, which in the authors' experience have contributed to improved outcomes. Current literature regarding indications and outcomes is limited and controversial. The proposed benefits of soft-tissue interposition arthroplasty of the hallux metatarsophalangeal joint for patients with prior failed implant arthroplasty are improved pain scores and preservation of range of motion. Level of Evidence: Level V, technique guide.

Ventilation/perfusion single-photon emission computed tomography: a service evaluation.

OBJECTIVES: To identify the positive rate and negative predictive value (NPV) of our ventilation/perfusion (V/Q) single-photon emission computed tomography (SPECT) service as respective markers of overcalling (false positives) and undercalling (false negatives). We also identified the indeterminate rate as an indicator of the technical quality of the scans and reporter confidence. PATIENTS AND METHODS: V/Q SPECT studies carried out over 5 years were classified into positive, negative and indeterminate results. Patients who had died or had pulmonary emboli on imaging within 3 months of a negative V/Q SPECT were identified as false negatives, from which the NPV was calculated. The total number of positive and indeterminate studies as a proportion of all studies was calculated as the positive and indeterminate rates. RESULTS: The positive rate, NPV and indeterminate rates in nonpregnant patients were 24, 98.7-100 and 3.6%, respectively. The positive rate, NPV and indeterminate rates in pregnant patients were 6.8, 100 and 2.3%, respectively. CONCLUSION: The positive rate and NPV for nonpregnant patients were similar to the published literature. This suggests that we provide a safe service. The indeterminate rate was slightly higher than the stated guidelines. The study shows that the positive rate and NPV are achievable indicators of potential overcalling and undercalling in a V/Q SPECT service.This is also one of the first studies to report a positive rate in pregnant patients undergoing V/Q SPECT that other institutions can use as a standard when evaluating their services.

Incidental Papillary Bladder Carcinoma on 18F-Fluoromethylcholine PET/CT Undertaken to Evaluate Prostate Malignancy.

FDG PET is known to have a low sensitivity for the detection of prostate and bladder tumors because of high levels of urinary excretion, which potentially obscures sites of disease. Fluoromethylcholine PET has a higher sensitivity for the detection of metastatic prostate cancer compared with F-FDG PET, partly because of lower levels of urinary excretion. We present a case of a patient who underwent F-fluoromethylcholine PET for possible recurrent prostate cancer. The study identified an incidental, avid metachronous bladder tumor. We discuss the potential use of fluoromethylcholine PET in the detection of bladder tumors.

Long-term liver-specific functions of hepatocytes in electrospun chitosan nanofiber scaffolds coated with fibronectin.

In this study, a new 3D liver model was developed using biomimetic nanofiber scaffolds and co-culture system consisting of hepatocytes and fibroblasts for the maintenance of long-term liver functions. The chitosan nanofiber scaffolds were fabricated by the electrospinning technique. To enhance cellular adhesion and spreading, the surfaces of the chitosan scaffolds were coated with fibronectin (FN) by adsorption and evaluated for various cell types. Cellular phenotype, protein expression, and liver-specific functions were extensively characterized by immunofluorescent and histochemical stainings, albumin enzyme-linked immunosorbent assay and Cytochrome p450 detoxification assays, and scanning electron microscopy. The electrospun chitosan scaffolds exhibited a highly porous and randomly oriented nanofibrous structure. The FN coating on the surface of the chitosan nanofibers significantly enhanced cell attachment and spreading, as expected, as surface modification with this cell adhesion molecule on the chitosan surface is important for focal adhesion formation and integrin binding. Comparison of hepatocyte mono-cultures and co-cultures in 3D culture systems indicated that the hepatocytes in co-cultures formed colonies and maintained their morphologies and functions for prolonged periods of time. The 3D liver tissue model developed in this study will provide useful tools toward the development of engineered liver tissues for drug screening and tissue engineering applications. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 2119-2128, 2017.

Long-term hepatitis B infection in a scalable hepatic co-culture system.

Hepatitis B virus causes chronic infections in 250 million people worldwide. Chronic hepatitis B virus carriers are at risk of developing fibrosis, cirrhosis, and hepatocellular carcinoma. A prophylactic vaccine exists and currently available antivirals can suppress but rarely cure chronic infections. The study of hepatitis B virus and development of curative antivirals are hampered by a scarcity of models that mimic infection in a physiologically relevant, cellular context. Here, we show that cell-culture and patient-derived hepatitis B virus can establish persistent infection for over 30 days in a self-assembling, primary hepatocyte co-culture system. Importantly, infection can be established without antiviral immune suppression, and susceptibility is not donor dependent. The platform is scalable to microwell formats, and we provide proof-of-concept for its use in testing entry inhibitors and antiviral compounds.The lack of models that mimic hepatitis B virus (HBV) infection in a physiologically relevant context has hampered drug development. Here, Winer et al. establish a self-assembling, primary hepatocyte co-culture system that can be infected with patient-derived HBV without further modifications.