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At the quadrangular joint (QAJ) of the carpus, a rare bony protuberance called carpal boss (CB) may occur. This bone abnormality may be due to osteophytes development or os styloideum. Symptomatic patients may complain pain, swelling, and restrictions in hand motion. These symptoms result from joint degenerative-inflammatory changes, development of ganglion cyst/bursitis, or tendons pathology. Correct diagnosis and appropriate management can be achieved through high-resolution ultrasonography (HR-US). The purpose of this review is to define the pathology spectrum around and within the QAJ in CB. The role of HR-US is highlighted and the standard technique for the QAJ assessment is described., (© 2024 Wiley Periodicals LLC.)

Purpose: Changes in quantitative magnetic resonance imaging (qMRI) are frequently observed during chemotherapy or radiation therapy (RT). It is hypothesized that qMRI features are reflective of underlying tissue responses. It's unknown what underlying genomic characteristics underly qMRI changes. We hypothesized that qMRI changes may correlate with DNA damage response (DDR) capacity within human tumors. Therefore, we designed the current study to correlate qMRI changes from daily RT treatment with underlying tumor transcriptomic profiles., Methods and Materials: Study participants were prospectively enrolled (National Clinical Trial 03500081). RNA expression levels for 757 genes from pretreatment biopsies were obtained using a custom panel that included signatures of radiation sensitivity and DDR. Daily qMRI data were obtained from a 1.5 Tesla MR linear accelerator. Using these images, d-slow, d-star, perfusion, and apparent diffusion coefficient-mean values in tumors were plotted per-fraction, over time, and associated with genomic pathways., Results: A total of 1022 qMRIs were obtained from 39 patients and both genomic data and qMRI data from 27 total patients. For 20 of those patients, we also generated normal tissue transcriptomic data. Radio sensitivity index values most closely associated with tissue of origin. Multiple genomic pathways including DNA repair, peroxisome, late estrogen receptor responses, KRAS signaling, and UV response were significantly associated with qMRI feature changes (P < .001)., Conclusions: Genomic pathway associations across metabolic, RT sensitivity, and DDR pathways indicate common tumor biology that may correlate with qMRI changes during a course of treatment. Such data provide hypothesis-generating novel mechanistic insight into the biologic meaning of qMRI changes during treatment and enable optimal selection of imaging biomarkers for biologically MR-guided RT., (Published by Elsevier Inc.)

Objectives: To study the medial meniscus extrusion (MME) in subjects with and without medial meniscal tears on magnetic resonance imaging (MRI), supine ultrasound (US), and weight-bearing US., Methods: Forty-seven cases (mean age 43.7 years) with medial meniscus tears and 53 healthy controls (mean age 36.6 years) were assessed. Two experienced sonographers performed the US evaluations, and a fellowship-trained musculoskeletal radiologist assessed the menisci on MRI. Independent and paired T-tests and ICC were used for statistical analyses., Results: On supine US, the mean MME was 3.9 mm for the cases and 2.3 mm for the controls (p < 0.001). On weight-bearing US, the values were 4.2 and 2.8 mm (p < 0.001), and on MRI 3.0 and 2.0 mm (p < 0.001), respectively. The mean difference between supine and weight-bearing US extrusion was 0.38 mm for the cases and 0.49 mm for the controls (p = 0.291). Correlation between supine US and MRI MME measurements was good (ICC = 0.660, CIs [0.533-0.758])., Conclusions: MME can be assessed using US with good correlation to MRI. US-observed extrusion was significantly increased in supine and standing positions for medial meniscus tears. The mean difference between examination positions was reduced with medial meniscus tears although this result was statistically insignificant., (© 2024 The Authors. Journal of Clinical Ultrasound published by Wiley Periodicals LLC.)

Objective: To perform a systematic literature review on the diagnostic utility of 3D MRI sequences in the assessment of central canal, recess and foraminal stenosis in the spine., Methods: The databases PubMed, MEDLINE (via OVID) and The Cochrane Central Register of Controlled Trials, were searched for studies that investigated the diagnostic use of 3D MRI to evaluate stenoses in various parts of the spine in humans. Three reviewers examined the literature and conducted systematic review according to PRISMA 2020 guidelines., Results: Thirty studies were retrieved from 2 595 publications for this systematic review. The overall diagnostic performance of 3D MRI outperformed the conventional 2D MRI with reported sensitivities ranging from 79 to 100% and specificities ranging from 86 to 100% regarding the evaluation of central, recess and foraminal stenoses. In general, high level of agreement (both intra- and interrater) regarding visibility and pathology on 3D sequences was reported. Studies show that well-optimized 3D sequences allow the use of higher spatial resolution, similar scan time and increased SNR and CNR when compared to corresponding 2D sequences. However, the benefit of 3D sequences is in the additional information provided by them and in the possibility to save total protocol scan times., Conclusion: The literature on the spine 3D MRI assessment of stenoses is heterogeneous with varying MRI protocols and diagnostic results. However, the 3D sequences offer similar or superior detection of stenoses with high reliability. Especially, the advantage of 3D MRI seems to be the better evaluation of recess stenoses., (© 2024. The Author(s).)

Androgen receptor (AR) drives prostate cancer (PC) growth and progression, and targeting AR signaling is the mainstay of pharmacological therapies for PC. Resistance develops relatively fast as a result of refueled AR activity. A major gap in the field is the lack of understanding of targetable mechanisms that induce persistent AR expression in castrate-resistant PC (CRPC). This study uncovers an unexpected function of active Stat5 signaling, a known promoter of PC growth and clinical progression, as a potent inducer of AR gene transcription. Stat5 suppression inhibited AR gene transcription in preclinical PC models and reduced the levels of wild-type, mutated, and truncated AR proteins. Pharmacological Stat5 inhibition by a specific small-molecule Stat5 inhibitor down-regulated Stat5-inducible genes as well as AR and AR-regulated genes and suppressed PC growth. This work introduces the concept of Stat5 as an inducer of AR gene transcription in PC. Pharmacological Stat5 inhibitors may represent a new strategy for suppressing AR and CRPC growth.

Traditionally, osteoarthritis (OA) is diagnosed with the clinical examination supplemented by the conventional radiography (CR). In the research literature, the role of ultrasound (US) imaging in the diagnostics of OA has risen steadily during the last two decades. US imaging is cheap and globally widely available often already in primary healthcare. Here, we reviewed the most essential US literature focusing on OA diagnostics and progression prediction using the various search engines. Starting from the year 2000, our search provided 1 445 journal articles. After reviewing the abstracts, 89 articles were finally included. Most of the reviewed articles focused on the imaging of knee and hand OA, whereas only a minority dealt with the imaging of hip, ankle, midfoot, acromioclavicular, and temporomandibular joints. Overall, during the last 20 years, the use of US imaging for OA assessment has increased in the scientific literature. In knee and hand joints, US imaging has been reported to be a promising tool to evaluate OA changes. Furthermore, the reproducibility of US as well as its association to MRI findings are excellent. Importantly, US seems to even outperform CR in certain aspects, such as detection of osteophytes, joint inflammation, meniscus protrusion, and localized cartilage damage (especially at the medial femoral condyle and sulcus area). Based on the reviewed literature, US can be truly considered as a complementary tool to CR in the clinical setup for OA diagnostics. New technical developments may even enhance the diagnostic value of the US in the future., (© 2023. The Author(s).)

Objectives: To evaluate extensor carpi ulnaris (ECU) tendon pathology and ulnar styloid process bone marrow edema (BME) as diagnostic MRI markers for peripheral triangular fibrocartilage complex (TFCC) tears., Methods: One hundred thirty-three patients (age range 21-75, 68 females) with wrist 1.5-T MRI and arthroscopy were included in this retrospective case-control study. The presence of TFCC tears (no tear, central perforation, or peripheral tear), ECU pathology (tenosynovitis, tendinosis, tear or subluxation), and BME at the ulnar styloid process were determined on MRI and correlated with arthroscopy. Cross-tabulation with chi-square tests, binary logistic regression with odds ratios (OR), and sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were used to describe diagnostic efficacy., Results: On arthroscopy, 46 cases with no TFCC tear, 34 cases with central perforations, and 53 cases with peripheral TFCC tears were identified. ECU pathology was seen in 19.6% (9/46) of patients with no TFCC tears, in 11.8% (4/34) with central perforations and in 84.9% (45/53) with peripheral TFCC tears (p < 0.001); the respective numbers for BME were 21.7% (10/46), 23.5% (8/34), and 88.7% (47/53) (p < 0.001). Binary regression analysis showed additional value from ECU pathology and BME in predicting peripheral TFCC tears. The combined approach with direct MRI evaluation and both ECU pathology and BME yielded a 100% positive predictive value for peripheral TFCC tear as compared to 89% with direct evaluation alone., Conclusions: ECU pathology and ulnar styloid BME are highly associated with peripheral TFCC tears and can be used as secondary signs to diagnose tears., Key Points: • ECU pathology and ulnar styloid BME are highly associated with peripheral TFCC tears and can be used as secondary signs to confirm the presence of TFCC tears. • If there is a peripheral TFCC tear on direct MRI evaluation and in addition both ECU pathology and BME on MRI, the positive predictive value is 100% that there will be a tear on arthroscopy compared to 89% with direct evaluation alone. • If there is no peripheral TFCC tear on direct evaluation and neither ECU pathology nor BME on MRI, the negative predictive value is 98% that there will be no tear on arthroscopy compared to 94% with direct evaluation alone., (© 2023. The Author(s).)

Purpose: T-cell-mediated cytotoxicity is suppressed when programmed cell death-1 (PD-1) is bound by PD-1 ligand-1 (PD-L1) or PD-L2. Although PD-1 inhibitors have been approved for triple-negative breast cancer, the lower response rates of 25%-30% in estrogen receptor-positive (ER+) breast cancer will require markers to identify likely responders. The focus of this study was to evaluate whether PD-L2, which has higher affinity than PD-L1 for PD-1, is a predictor of early recurrence in ER+ breast cancer., Methods: PD-L2 protein levels in cancer cells and stromal cells of therapy-naive, localized or locoregional ER+ breast cancers were measured retrospectively by quantitative immunofluorescence histocytometry and correlated with progression-free survival (PFS) in the main study cohort (n = 684) and in an independent validation cohort (n = 273). All patients subsequently received standard-of-care adjuvant therapy without immune checkpoint inhibitors., Results: Univariate analysis of the main cohort revealed that high PD-L2 expression in cancer cells was associated with shorter PFS (hazard ratio [HR], 1.8; 95% CI, 1.3 to 2.6; P = .001), which was validated in an independent cohort (HR, 2.3; 95% CI, 1.1 to 4.8; P = .026) and remained independently predictive after multivariable adjustment for common clinicopathological variables (HR, 2.0; 95% CI, 1.4 to 2.9; P < .001). Subanalysis of the ER+ breast cancer patients treated with adjuvant chemotherapy (n = 197) revealed that high PD-L2 levels in cancer cells associated with short PFS in univariate (HR, 2.5; 95% CI, 1.4 to 4.4; P = .003) and multivariable analyses (HR, 3.4; 95% CI, 1.9 to 6.2; P < .001)., Conclusion: Up to one third of treatment-naive ER+ breast tumors expressed high PD-L2 levels, which independently predicted poor clinical outcome, with evidence of further elevated risk of progression in patients who received adjuvant chemotherapy. Collectively, these data warrant studies to gain a deeper understanding of PD-L2 in the progression of ER+ breast cancer and may provide rationale for immune checkpoint blockade for this patient group.

Background: Diffusion-weighted imaging (DWI) is commonly used to detect prostate cancer, and a major clinical challenge is differentiating aggressive from indolent disease., Purpose: To compare 14 site-specific parametric fitting implementations applied to the same dataset of whole-mount pathologically validated DWI to test the hypothesis that cancer differentiation varies with different fitting algorithms., Study Type: Prospective., Population: Thirty-three patients prospectively imaged prior to prostatectomy., Field Strength/sequence: 3 T, field-of-view optimized and constrained undistorted single-shot DWI sequence., Assessment: Datasets, including a noise-free digital reference object (DRO), were distributed to the 14 teams, where locally implemented DWI parameter maps were calculated, including mono-exponential apparent diffusion coefficient (MEADC), kurtosis (K), diffusion kurtosis (DK), bi-exponential diffusion (BID), pseudo-diffusion (BID*), and perfusion fraction (F). The resulting parametric maps were centrally analyzed, where differentiation of benign from cancerous tissue was compared between DWI parameters and the fitting algorithms with a receiver operating characteristic area under the curve (ROC AUC)., Statistical Test: Levene's test, P < 0.05 corrected for multiple comparisons was considered statistically significant., Results: The DRO results indicated minimal discordance between sites. Comparison across sites indicated that K, DK, and MEADC had significantly higher prostate cancer detection capability (AUC range = 0.72-0.76, 0.76-0.81, and 0.76-0.80 respectively) as compared to bi-exponential parameters (BID, BID*, F) which had lower AUC and greater between site variation (AUC range = 0.53-0.80, 0.51-0.81, and 0.52-0.80 respectively). Post-processing parameters also affected the resulting AUC, moving from, for example, 0.75 to 0.87 for MEADC varying cluster size., Data Conclusion: We found that conventional diffusion models had consistent performance at differentiating prostate cancer from benign tissue. Our results also indicated that post-processing decisions on DWI data can affect sensitivity and specificity when applied to radiological-pathological studies in prostate cancer., Level of Evidence: 1 TECHNICAL EFFICACY: Stage 3., (© 2021 The Authors. Journal of Magnetic Resonance Imaging published by Wiley Periodicals LLC on behalf of International Society for Magnetic Resonance in Medicine.)

Objectives: To determine the diagnostic performance of ultrasonography (US) for evaluation of the ankle joint osteoarthritic (OA) changes. Cone-beam computed tomography (CT) was used as the gold standard and US performance was compared with conventional radiography (CR). As a secondary aim, associations between the imaging findings and ankle symptoms were assessed., Methods: US was performed to 51 patients with ankle OA. Every patient had prior ankle CR and underwent cone-beam CT during the same day as US examination. On US, effusion/synovitis, osteophytes, talar cartilage damage, and tenosynovitis were evaluated. Comparison to respective imaging findings on CR and cone-beam CT was then performed. Single radiologist blinded to other modalities assessed all the imaging studies. Symptoms questionnaire, the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), was available for 48 patients., Results: US detected effusion/synovitis of the talocrural joint with 45% sensitivity and 90% specificity. For the detection of anterior talocrural osteophytes, US sensitivity was 78% and specificity 79%. For the medial talocrural osteophytes, they were 39 and 83%, and for the lateral talocrural osteophytes 54 and 100%, respectively. Considering cartilage damage of the talus, US yielded a low sensitivity of 18% and high specificity of 97%. Overall, the performance of US was only moderate and comparable to CR. The imaging findings showed only weak associations with ankle symptoms., Conclusions: The ability of US to detect ankle OA is only moderate. Interestingly, performance of CR also remained moderate. The associations between imaging findings and WOMAC score seem to be weak in ankle OA., (© 2021 The Authors. Journal of Ultrasound in Medicine published by Wiley Periodicals LLC on behalf of American Institute of Ultrasound in Medicine.)

Purpose: We examine the outcomes following operative treatment of intra-articular fracture combined with medial patellofemoral ligament (MPFL) reconstruction after patella dislocation., Methods: Patients were retrospectively identified from medical records using diagnostic and surgical procedure codes. Radiological anatomical parameters and bony abnormalities of injured knees were assessed from magnetic resonance images (MRI). Inclusion criteria were traumatic patellar dislocation with chondral or osteochondral fracture and MPFL rupture, operative treatment of a chondral or osteochondral fracture combined with MPFL reconstruction, and minimum follow-up of 2 years. Outcomes were measured using the Kujala score, Tegner activity scale, and the Knee injury and Osteoarthritis Outcome Score Quality-of-Life subscale (KOOS-QLS)., Results: During 2012 and 2015, 322 patients were treated because of patellar dislocation. Thirty-three patients had chondral or osteochondral fracture. Eleven patients (five males and six females) with a mean [standard deviation (SD)] age of 17.0 (6.5) years at the time of surgery met the inclusion criteria and were included. Five of the 11 patients had a subchondral and six an osteochondral fracture. Eight patients had a fracture in the patella and three in the femur. All patients had bony abnormalities in the knee. Nine out of 11 patients scored over 90/100 points on the Kujala scale and had good results on the Tegner scale [before surgery 5.0 (2.7) points versus after surgery 5.3 (1.6) points] and the KOOS-QLS [4.1 (4.2) points] outcome measures., Conclusion: The removal or fixation of the fracture fragment combined with MPFL reconstruction is a feasible option in the treatment of symptomatic osteochondral or subchondral fragment in traumatic patellar dislocation. The short-term outcomes are encouraging., Level of Evidence: Level IV, retrospective case series., (© 2022. The Author(s).)

Study Design: A cross-sectional study of the Northern Finland Birth Cohort 1966 (NFBC1966)., Objective: To evaluate the association of lumbosacral transitional vertebrae (LSTV) with low back pain (LBP) and associated degenerative findings using magnetic resonance (MR) imaging., Summary of Background Data: LSTV is a common finding with a prevalence of 10% to 29%. LSTV causes biomechanical alterations leading to accelerated lumbar degeneration. However, its association with degenerative findings on MRI and LBP is unclear., Methods: One thousand four hundred sixty eight lumbar spine MRI scans from the NFBC1966 acquired at a mean age of 47 years were assessed for the presence of LSTV and degenerative changes. Castellvi classification was utilized to identify LSTV anatomy. Additionally, 100 controls without LSTV were collected. Self-reported LBP with a duration of more than 30 days in the past year was deemed clinically relevant. For the statistical analyses, chi square test, independent samples t test and multinomial logistic regression analyses were used., Results: LSTV was found in 310 (21.1%) subjects. After adjusting for age, sex, and disc degeneration (DD) sum, subjects with Castellvi type III reported prolonged LBP significantly more frequently than the controls (odds ratio [OR] = 8.9, P = 0.001). We observed a higher prevalence of facet degeneration (FD) at all levels from L3/L4 to L5/S1 in type I, and L3/L4 to L4/L5 in types II-IV. DD was more prevalent at L4/L5 in types II-IV. Disc protrusion/extrusion occurred more frequently at L3/L4 and L4/L5 in type II, and at L3/L4 in type III. Castellvi type II had a higher prevalence of type 1 Modic changes at levels from L3/L4 to L4/L5., Conclusion: LSTVs were a common finding within this study, and Castellvi type III LSTVs were associated with LBP. Degenerative findings were associated with LSTV anatomy and occurred more commonly above the transitional level.Level of Evidence: 3., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Tumor-associated macrophages (TAMs) promote progression of breast cancer and other solid malignancies via immunosuppressive, pro-angiogenic and pro-metastatic effects. Tumor-promoting TAMs tend to express M2-like macrophage markers, including CD163. Histopathological assessments suggest that the density of CD163-positive TAMs within the tumor microenvironment is associated with reduced efficacy of chemotherapy and unfavorable prognosis. However, previous analyses have required research-oriented pathologists to visually enumerate CD163+ TAMs, which is both laborious and subjective and hampers clinical implementation. Objective, operator-independent image analysis methods to quantify TAM-associated information are needed. In addition, since M2-like TAMs exert local effects on cancer cells through direct juxtacrine cell-to-cell interactions, paracrine signaling, and metabolic factors, we hypothesized that spatial metrics of adjacency of M2-like TAMs to breast cancer cells will have further information value. Immunofluorescence histo-cytometry of CD163+ TAMs was performed retrospectively on tumor microarrays of 443 cases of invasive breast cancer from patients who subsequently received adjuvant chemotherapy. An objective and automated algorithm was developed to phenotype CD163+ TAMs and calculate their density within the tumor stroma and derive several spatial metrics of interaction with cancer cells. Shorter progression-free survival was associated with a high density of CD163+ TAMs, shorter median cancer-to-CD163+ nearest neighbor distance, and a high number of either directly adjacent CD163+ TAMs (within juxtacrine proximity <12 μm to cancer cells) or communicating CD163+ TAMs (within paracrine communication distance <250 μm to cancer cells) after multivariable adjustment for clinical and pathological risk factors and correction for optimistic bias due to dichotomization.

Androgen deprivation therapy (ADT) for metastatic and high-risk prostate cancer (PC) inhibits growth pathways driven by the androgen receptor (AR). Over time, ADT leads to the emergence of lethal castrate-resistant PC (CRPC), which is consistently caused by an acquired ability of tumors to re-activate AR. This has led to the development of second-generation anti-androgens that more effectively antagonize AR, such as enzalutamide (ENZ). However, the resistance of CRPC to ENZ develops rapidly. Studies utilizing preclinical models of PC have established that inhibition of the Jak2-Stat5 signaling leads to extensive PC cell apoptosis and decreased tumor growth. In large clinical cohorts, Jak2-Stat5 activity predicts PC progression and recurrence. Recently, Jak2-Stat5 signaling was demonstrated to induce ENZ-resistant PC growth in preclinical PC models, further emphasizing the importance of Jak2-Stat5 for therapeutic targeting for advanced PC. The discovery of the Jak2V617F somatic mutation in myeloproliferative disorders triggered the rapid development of Jak1/2-specific inhibitors for a variety of myeloproliferative and auto-immune disorders as well as hematological malignancies. Here, we review Jak2 inhibitors targeting the mutated Jak2V617F vs. wild type (WT)-Jak2 that are currently in the development pipeline. Among these 35 compounds with documented Jak2 inhibitory activity, those with potency against WT-Jak2 hold strong potential for advanced PC therapy.

To evaluate the acoustic emissions (AE) and kinematic instability (KI) of the osteoarthritic (OA) knee joints, and to compare these signals to radiographic findings. Sixty-six female and 43 male participants aged 44-67 were recruited. On radiography, joint-space narrowing, osteophytes and Kellgren-Lawrence (KL) grade were evaluated. Based on radiography, 54 subjects (the study group) were diagnosed with radiographic OA (KL-grade ≥ 2) while the remaining 55 subjects (KL-grade < 2) formed the control group. AE and KI were recorded with a custom-made prototype and compared with radiographic findings using area-under-curve (AUC) and independent T-test. Predictive logistic regression models were constructed using leave-one-out cross validation. In females, the parameters reflecting consistency of the AE patterns during specific tasks, KI, BMI and age had a significant statistical difference between the OA and control groups (p = 0.001-0.036). The selected AE signals, KI, age and BMI were used to construct a predictive model for radiographic OA with AUC of 90.3% (95% CI 83.5-97.2%) which showed a statistical improvement of the reference model based on age and BMI, with AUC of 84.2% (95% CI 74.8-93.6%). In males, the predictive model failed to improve the reference model. AE and KI provide complementary information to detect radiographic knee OA in females., (© 2021. The Author(s).)

Most breast cancer deaths are caused by estrogen receptor-α–positive (ER + ) disease. Preclinical progress is hampered by a shortage of therapy-naïve ER + tumor models that recapitulate metastatic progression and clinically relevant therapy resistance. Human prolactin (hPRL) is a risk factor for primary and metastatic ER + breast cancer. Because mouse prolactin fails to activate hPRL receptors, we developed a prolactin-humanized Nod-SCID-IL2Rγ (NSG) mouse (NSG-Pro) with physiological hPRL levels. Here, we show that NSG-Pro mice facilitate establishment of therapy-naïve, estrogen-dependent PDX tumors that progress to lethal metastatic disease. Preclinical trials provide first-in-mouse efficacy of pharmacological hPRL suppression on residual ER + human breast cancer metastases and document divergent biology and drug responsiveness of tumors grown in NSG-Pro versus NSG mice. Oncogenomic analyses of PDX lines in NSG-Pro mice revealed clinically relevant therapy-resistance mechanisms and unexpected, potently actionable vulnerabilities such as DNA-repair aberrations. The NSG-Pro mouse unlocks previously inaccessible precision medicine approaches for ER + breast cancers.

Panc reatic ductal adenocarcinoma (PDAC) is a devastating malignancy. There have been few advances that have substantially improved overall survival in the past several years. On its current trajectory, the deaths from PDAC are expected to cross that from all gastrointestinal cancers combined by 2030. Radiation therapy is a technically very complex modality that bridges multiple different treatment strategies. It represents a hybrid among advanced diagnostic imaging, local (often ablative) intervention, and heterogeneous biological mechanisms contributing to normal and oncologic cell kill. In this article, we bring an overview of the several promising strategies that are currently being investigated to improve outcomes using radiation therapy for patients with PDAC., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: Ultrasonography (US) has a promising role in evaluating the knee joint, but capability to visualize the femoral articular cartilage needs systematic evaluation. We measured the extent of this acoustic window by comparing standardized US images with the corresponding MRI views of the femoral cartilage., Design: Ten healthy volunteers without knee pathology underwent systematic US and MRI evaluation of both knees. The femoral cartilage was assessed on the oblique transverse axial plane with US and with 3D MRI. The acoustic window on US was compared to the corresponding views of the femoral sulcus and both condyles on MRI. The mean imaging coverage of the femoral cartilage and the cartilage thickness measurements on US and MRI were compared., Results: Mean imaging coverage of the cartilage of the medial femoral condyle was 66% (range 54%-80%) and on the lateral femoral condyle 37% (range 25%-51%) compared with MRI. Mean cartilage thickness measurement in the femoral sulcus was 3.17 mm with US and 3.61 mm with MRI (14.0% difference). The corresponding measurements in the medial femoral condyle were 1.95 mm with US and 2.35 mm with MRI (21.0% difference), and in the lateral femoral condyle, they were 2.17 mm and 2.73 mm (25.6% difference), respectively., Conclusion: Two-thirds of the articular cartilage of the medial femoral condyle, and one-third in the lateral femoral condyle, can be assessed with US. The cartilage thickness measurements seem to be underestimated by US. These results show promise for the evaluation of the weight-bearing cartilage of the medial femoral condyle with US., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2021 Kyösti Kauppinen et al.)

Background: Avascular osteonecrosis of the femoral head (AVNFH) is an ischemic condition which despite different treatments often leads to collapse of the femoral head and to total hip arthroplasty. However, the magnetic resonance imaging findings predisposing to disease progression and total hip arthroplasty are somewhat elusive., Purpose: To evaluate the magnetic resonance imaging findings of AVNFH and to assess the patterns of findings which may predict total hip arthroplasty., Materials and Methods: A retrospective study was conducted with a total of 18 diagnosed AVNFH treated with core decompression combined with intraosseous stem cell treatment. After treatment, magnetic resonance imaging follow-ups were done at three-month and one-year follow-up or until total hip arthroplasty. Association Research Circulation Osseous classification and magnetic resonance imaging findings such as the size and the location of the AVNFH, bone marrow edema in femoral neck, effusion and subchondral fracture were evaluated., Results: Hips advancing to total hip arthroplasty have more often bone marrow edema in femoral neck (90% vs. 0%), adjacent to necrotic lesion (100% vs. 43%) and in acetabulum (90% vs. 14%), but also subchondral fractures (70% vs. 0%), effusion (80% vs. 29%), and synovitis (80% vs. 14,3%). The greater size and the lateral weight-bearing location of the necrotic lesion also predicted future total hip arthroplasty., Conclusion: Hips advancing to total hip arthroplasty have often a combination of pathognomonic AVNFH imaging findings compared to hips not advancing to total hip arthroplasty., Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Foundation Acta Radiologica 2021.)

Aim of this study was to assess the US findings of patients with late-stage hip OA undergoing total hip arthroplasty (THA), and to associate the US findings with conventional radiography (CR) and intraoperative findings. Moreover, the inter-rater reliability of hip US, and association between the US and Oxford Hip Score (OHS) were evaluated. Sixty-eight hips were included, and intraoperative findings were available on 48 hips. Mean patient age was 67.6 years and 38% were males. OA findings-osteophytes at femoral collum and anterosuperior acetabulum, femoral head deformity and effusion-were assessed on US, CR and THA. The diagnostic performance of US and CR was compared by applying the THA findings as the gold standard. Osteoarthritic US findings were very common, but no association between the US findings and OHS was observed. The pooled inter-rater reliability (n = 65) varied from moderate to excellent (k = 0.538-0.815). When THA findings were used as the gold standard, US detected femoral collum osteophytes with 95% sensitivity, 0% specificity, 81% accuracy, and 85% positive predictive value. Concerning acetabular osteophytes, the respective values were 96%, 0%, 88% and 91%. For the femoral head deformity, they were 92%, 36%, 38% and 83%, and for the effusion 49%, 85%, 58% and 90%, respectively. US provides similar detection of osteophytes as does CR. On femoral head deformity, performance of the US is superior to CR. The inter-rater reliability of the US evaluation varies from moderate to excellent, and no association between US and OHS was observed in this patient cohort.

Stat5 is of significant interest in the search for new therapeutics for prostate cancer (PC) and hematopoietic disorders. We evaluated the transcriptomic specificity of the Stat5a/b inhibitor IST5-002 (IST5) in PC, defined more closely its mechanisms of action, and investigated the in vivo toxicity of IST5 for further optimization for clinical development. The transcriptomic specificity of IST5 vs. genetic Stat5 knockdown was evaluated by RNA-seq analysis, which showed high similarity with the Pearson correlation coefficient ranging from 0.98-0.99. The potency of IST5 vs. its derivative lacking the phosphate group in suppressing Stat5 was evaluated in two separate but complementary assays. The inhibitory activity of IST5 against kinases was investigated in cell-free assays followed by more focused evaluation in a cell-based assay. IST5 has no specific inhibitory activity against 54 kinases, while suppressing Stat5 phosphorylation and subsequent dimerization in PC cells. The phosphate group was not critical for the biological activity of IST5 in cells. The acute, sub-chronic and chronic toxicity studies of IST5 were carried out in mice. IST5 did not cause any significant toxic effects or changes in the blood profiles. The present work supports further optimization of IST5 for oral bioavailability for clinical development for therapies for solid tumors, hematological and myeloproliferative disorders.

A number of solid tumors are treated with radiation therapy (RT) as a curative modality. At the same time, for certain types of cancers the applicable doses of RT are not high enough to result in a successful eradication of cancer cells. This is often caused by limited pharmacological tools and strategies to selectively sensitize tumors to RT while simultaneously sparing normal tissues from RT. We present an outline of a novel strategy for RT sensitization of solid tumors utilizing Jak inhibitors. Here, recently published pre-clinical data are reviewed which demonstrate the promising role of Jak inhibition in sensitization of tumors to RT. A wide number of currently approved Jak inhibitors for non-malignant conditions are summarized including Jak inhibitors currently in clinical development. Finally, intersection between Jak/Stat and the levels of serum cytokines are presented and discussed as they relate to susceptibility to RT., (Copyright © 2020. Published by Elsevier Ltd.)

Purpose: Prostate cancer primarily arises from the glandular epithelium. Histomophometric techniques have been used to assess the glandular epithelium in automated detection and classification pipelines; however, they are often rigid in their implementation, and their performance suffers on large datasets where variation in staining, imaging, and preparation is difficult to control. The purpose of this study is to quantify performance of a pixelwise segmentation algorithm that was trained using different combinations of weak and strong stroma, epithelium, and lumen labels in a prostate histology dataset. Approach: We have combined weakly labeled datasets generated using simple morphometric techniques and high-quality labeled datasets from human observers in prostate biopsy cores to train a convolutional neural network for use in whole mount prostate labeling pipelines. With trained networks, we characterize pixelwise segmentation of stromal, epithelium, and lumen (SEL) regions on both biopsy core and whole-mount H&E-stained tissue. Results: We provide evidence that by simply training a deep learning algorithm on weakly labeled data generated from rigid morphometric methods, we can improve the robustness of classification over the morphometric methods used to train the classifier. Conclusions: We show that not only does our approach of combining weak and strong labels for training the CNN improve qualitative SEL labeling within tissue but also the deep learning generated labels are superior for cancer classification in a higher-order algorithm over the morphometrically derived labels it was trained on., (© The Authors. Published by SPIE under a Creative Commons Attribution 4.0 Unported License. Distribution or reproduction of this work in whole or in part requires full attribution of the original publication, including its DOI.)

Objectives: To assess the prevalence of lumbosacral transitional vertebra (LSTV) and associated spinal degenerative changes on abdominal CT scans in Caucasian population., Material and Methods: A total of 3855 abdominal CT scans of the year 2017 from a single hospital were retrospectively assessed for LSTV, disc degeneration (DD), and facet joint degeneration (FD). An age- and sex-matched 150-subject control group without LSTV was picked at random. Multivariable logistic regression was used for the analysis., Results: LSTV was found in 1101 (29%) scans: Castellvi type I in 68%, type II in 16%, type III in 13%, and type IV in 3% of scans. Age- and sex-adjusted prevalence of DD was significantly higher in Castellvi type II and III groups at multiple lumbar levels, and in IV group at L4/5 than in control group (p < 0.001-0.034). At L5/S1, the prevalence of DD was significantly higher in the control group than in type II, III, or IV groups (p < 0.001-0.017). After combining Castellvi types II, III, and IV into one group, significant differences were found at all lumbar levels except L2/3 (p < 0.001-0.016). Prevalence of FD was significantly higher at L4/5 in Castellvi groups I, II, and III than in the control group (p < 0.001-0.002). When Castellvi types II, III, and IV were combined into one group, significant differences were found at lumbar levels L2/3, L3/4, and L4/5 (p < 0.001-0.021)., Conclusion: Lumbosacral vertebrae of Castellvi types II, III, and IV are associated with greater lumbar degeneration, warranting meticulous evaluation of spinal anatomy, even on CT., Key Points: • Lumbosacral transitional vertebra is a common incidental finding on abdominal CT scans with a high prevalence of 29%. • When assessing whole lumbar spine, lumbosacral vertebrae of Castellvi types II, III, and IV were associated with greater lumbar degeneration, warranting careful evaluation of the lumbar spine on abdominal CT scans.

Purpose: To assess whether ultrasonographic (US) findings associate with clinical findings in severe knee osteoarthritis (OA). Association of US findings with side-of-knee pain and inter-reader agreement of knee US were also evaluated., Methods: One-hundred-two patients (in total 123 knees) with severe knee OA were recruited for this cross-sectional study. US was performed by a single observer, and on 53 knees by two independent observers to assess inter-reader reliability. Preoperative clinical data was available for 69 knees. Cutoff values were applied to dichotomize US and clinical findings. The Chi-square test, Mann-Whitney test, and prevalence- and bias-adjusted kappa (PABAK) were applied for statistical analyses., Results: Seven of 99 associations tested were statistically significant. Associations were observed between range of flexion and lateral femoral (P = .009) and tibial (P = .001) osteophytes, mediolateral instability and damage to the lateral femoral cartilage (P = .014) and damage to the lateral meniscus (P = .031), and alignment and damage to the lateral femoral cartilage (P < .001), lateral tibial osteophytes (P = .037), and damage to the lateral meniscus (P < .001). A strong association was observed between medial-sided pain and same-sided cartilage damage and osteophytes (P < .001). That inter-reader agreement was excellent on the medial side of the knee joint (PABAK = 0.811-0.887)., Conclusions: US findings show a rather poor association with clinical OA findings. Inter-reader agreement of knee US is excellent on the medial side., (© 2019 Wiley Periodicals, Inc.)

The second-generation antiandrogen, enzalutamide, is approved for castrate-resistant prostate cancer (CRPC) and targets androgen receptor (AR) activity in CRPC. Despite initial clinical activity, acquired resistance to enzalutamide arises rapidly and most patients develop terminal disease. Previous work has established Stat5 as a potent inducer of prostate cancer growth. Here, we investigated the significance of Jak2-Stat5 signaling in resistance of prostate cancer to enzalutamide. The levels of Jak2 and Stat5 mRNA, proteins and activation were evaluated in prostate cancer cells, xenograft tumors, and clinical prostate cancers before and after enzalutamide therapy. Jak2 and Stat5 were suppressed by genetic knockdown using lentiviral shRNA or pharmacologic inhibitors. Responsiveness of primary and enzalutamide-resistant prostate cancer to pharmacologic inhibitors of Jak2-Stat5 signaling was assessed in vivo in mice bearing prostate cancer xenograft tumors. Patient-derived prostate cancers were tested for responsiveness to Stat5 blockade as second-line treatment after enzalutamide ex vivo in tumor explant cultures. Enzalutamide-liganded AR induces sustained Jak2-Stat5 phosphorylation in prostate cancer leading to the formation of a positive feed-forward loop, where activated Stat5, in turn, induces Jak2 mRNA and protein levels contributing to further Jak2 activation. Mechanistically, enzalutamide-liganded AR induced Jak2 phosphorylation through a process involving Jak2-specific phosphatases. Stat5 promoted prostate cancer growth during enzalutamide treatment. Jak2-Stat5 inhibition induced death of prostate cancer cells and patient-derived prostate cancers surviving enzalutamide treatment and blocked enzalutamide-resistant tumor growth in mice. This work introduces a novel concept of a pivotal role of hyperactivated Jak2-Stat5 signaling in enzalutamide-resistant prostate cancer, which is readily targetable by Jak2 inhibitors in clinical development., (©2019 American Association for Cancer Research.)

Background: A significant fraction of prostate cancer patients experience post-radical prostatectomy (RP) biochemical recurrence (BCR). New predictive markers are needed for optimizing postoperative prostate cancer management. STAT5 is an oncogene in prostate cancer that undergoes amplification in 30% of prostate cancers during progression., Methods: We evaluated the significance of a positive status for nuclear STAT5 protein expression versus STAT5 locus amplification versus combined positive status for both in predicting BCR after RP in 300 patients., Results: Combined positive STAT5 status was associated with a 45% disadvantage in BCR in Kaplan-Meier survival analysis in all Gleason grade patients. Patients with Gleason grade group (GG) 2 and 3 prostate cancers and combined positive status for STAT5 had a more pronounced disadvantage of 55% to 60% at 7 years after RP in univariate analysis. In multivariate analysis, including the Cancer of the Prostate Risk Assessment Postsurgical nomogram (CAPRA-S) variables, combined positive STAT5 status was independently associated with a shorter BCR-free survival in all Gleason GG patients (HR, 2.34; P = 0.014) and in intermediate Gleason GG 2 or 3 patients (HR, 3.62; P = 0.021). The combined positive STAT5 status improved the predictive value of the CAPRA-S nomogram in both ROC-AUC analysis and in decision curve analysis for BCR., Conclusions: Combined positive status for STAT5 was independently associated with shorter disease-free survival in univariate analysis and was an independent predictor for BCR in multivariate analysis using the CAPRA-S variables in prostate cancer., Impact: Our results highlight potential for a novel precision medicine concept based on a pivotal role of STAT5 status in improving selection of prostate cancer patients who are candidates for early adjuvant interventions to reduce the risk of recurrence., (©2019 American Association for Cancer Research.)

Objective: To report patterns of MRI findings involving carpal boss and extensor carpi radialis brevis (ECRB) tendon insertion in individuals with overuse-related or post-traumatic wrist pain., Materials and Methods: Eighty-four MRI cases with carpal bossing between December 2006 and June 2015 were analyzed by two fellowship-trained musculoskeletal radiologists. The following MRI findings were reviewed: type of carpal bossing (bony prominence, partial coalition, os styloideum), insertion of ECRB tendon (to the 3rd metacarpal, to carpal boss or to both), bone marrow edema (BME), insertion site, and tenosynovitis/tendinosis of ECRB tendon. Clinical information on wrist pain was available on 68 patients., Results: Fused carpal bossing was detected in 21%, partial coalition in 35%, and os styloideum in 44% of the cases. Regional BME was observed in 64% of the cases. When BME specifically at the carpal boss was assessed, 78% of stable and 50% of unstable bosses showed BME (p = 0.035). ECRB tendon inserted on a carpal boss in 20%, on the 3rd metacarpal bone in 35%, and on both sites in 45% of the cases. As BME at the carpal boss was assessed, BME was detected at the respective insertion sites in 71%, 35%, and 66% of the cases (p = 0.015). Dorsal wrist pain was associated with BME as 75% of the patients had regional BME in the vicinity of the carpal boss (p = 0.006)., Conclusion: A spectrum ranging from complete fusion of a boss to an entirely unfused os styloideum exists with a variable ECRB insertional anatomy. BME at the carpal boss is a consistent MRI finding.

Purpose: To provide a narrative review of the most relevant original research published in 2017/2018 on osteoarthritis imaging., Methods: The PubMed database was used to recover all relevant articles pertaining to osteoarthritis and medical imaging published between 1 April 2017 and 31 March 2018. Review articles, case studies and in vitro or animal studies were excluded. The original publications were subjectively sorted based on relevance, novelty and impact., Results and Conclusions: The publication search yielded 1,155 references. In the assessed publications, the most common imaging modalities were radiography (N = 708) and magnetic resonance imaging (MRI) (355), followed by computed tomography (CT) (220), ultrasound (85) and nuclear medicine (17). An overview of the most important publications to the osteoarthritis (OA) research community is presented in this narrative review. Imaging studies play an increasingly important role in OA research, and have helped us to understand better the pathophysiology of OA. Radiography and MRI continue to be the most applied imaging modalities, while quantitative MRI methods and texture analysis are becoming more popular. The value of ultrasound in OA research has been demonstrated. Several multi-modality predictive models have been developed. Deep learning has potential for more automatic and standardized analyses in future OA imaging research., (Copyright © 2019 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.)

Prostate cancer is the most common noncutaneous cancer in men in the United States. The current paradigm for screening and diagnosis is imperfect, with relatively low specificity, high cost, and high morbidity. This study aims to generate new image contrasts by learning a distribution of unique image signatures associated with prostate cancer. In total, 48 patients were prospectively recruited for this institutional review board-approved study. Patients underwent multiparametric magnetic resonance imaging 2 weeks before surgery. Postsurgical tissues were annotated by a pathologist and aligned to the in vivo imaging. Radiomic profiles were generated by linearly combining 4 image contrasts (T2, apparent diffusion coefficient [ADC] 0-1000, ADC 50-2000, and dynamic contrast-enhanced) segmented using global thresholds. The distribution of radiomic profiles in high-grade cancer, low-grade cancer, and normal tissues was recorded, and the generated probability values were applied to a naive test set. The resulting Gleason probability maps were stable regardless of training cohort, functioned independent of prostate zone, and outperformed conventional clinical imaging (area under the curve [AUC] = 0.79). Extensive overlap was seen in the most common image signatures associated with high- and low-grade cancer, indicating that low- and high-grade tumors present similarly on conventional imaging.

The purpose of this study was to assess the effectiveness of the ultrasonography (US) on detecting osteoarthritis of the knee, and compare US and radiographic findings to intraoperative total knee arthroplasty (TKA) findings. Fifty-seven late-stage osteoarthritic knees undergoing TKA were evaluated with US and radiography. Standard knee US assessing femoral cartilage damage, osteophytes, effusion, synovitis, and meniscal extrusion was performed. On radiographs, osteophytes, joint space narrowing, and Kellgren-Lawrence grade were evaluated. Corresponding intra-operative findings were assessed during TKA as the gold standard. On the damage of the medial femoral condyle cartilage, the sensitivity of US was high (92%), whereas on the lateral condyle and sulcus area, sensitivities were 58% and 46%, respectively. On osteophytes, the detection rate of the US was remarkable especially on the medial side yielding sensitivities of 90-95%. The sensitivities for detecting effusion and synovitis were also excellent (97%). US detection rate of femoral cartilage damage was in concordance with the radiographic joint space narrowing. For the detection of osteophytes, US provided superior results to radiography particularly on the medial side. In conclusion, US can reliably assess the late-stage OA changes of the knee especially on the medial side of the knee joint.

Combining standard cytotoxic chemotherapy with BCR-ABL1 tyrosine kinase inhibitors (TKI) has greatly improved the upfront treatment of patients with Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL). However, due to the development of drug resistance through both BCR-ABL1-dependent and -independent mechanisms, prognosis remains poor. The STAT5 transcription factor is activated by BCR-ABL1 and by JAK2-dependent cytokine signaling; therefore, inhibiting its activity could address both mechanisms of resistance in Ph+ ALL. We show here that genetic and pharmacologic inhibition of STAT5 activity suppresses cell growth, induces apoptosis, and inhibits leukemogenesis of Ph+ cell lines and patient-derived newly diagnosed and relapsed/TKI-resistant Ph+ ALL cells ex vivo and in mouse models. STAT5 silencing decreased expression of the growth-promoting PIM-1 kinase, the apoptosis inhibitors MCL1 and BCL2, and increased expression of proapoptotic BIM protein. The resulting apoptosis of STAT5-silenced Ph+ BV173 cells was rescued by silencing of BIM or restoration of BCL2 expression. Treatment of Ph+ ALL cells, including samples from relapsed/refractory patients, with the PIM kinase inhibitor AZD1208 and/or the BCL2 family antagonist Sabutoclax markedly suppressed cell growth and leukemogenesis ex vivo and in mice. Together, these studies indicate that targeting STAT5 or STAT5-regulated pathways may provide a new approach for therapy development in Ph+ ALL, especially the relapsed/TKI-resistant disease. Significance: Suppression of STAT5 by BCL2 and PIM kinase inhibitors reduces leukemia burden in mice and constitutes a new potential therapeutic approach against Ph+ ALL, especially in tyrosine kinase inhibitor-resistant disease. Cancer Res; 78(20); 5793-807. ©2018 AACR ., (©2018 American Association for Cancer Research.)

Purpose: This study aims to combine multiparametric magnetic resonance imaging (MRI) and digitized pathology with machine learning to generate predictive maps of histologic features for prostate cancer localization., Methods and Materials: Thirty-nine patients underwent MRI prior to prostatectomy. After surgery, tissue was sliced according to MRI orientation using patient-specific 3-dimensionally printed slicing jigs. Whole-mount sections were annotated by our pathologist and digitally contoured to differentiate the lumen and epithelium. Slides were co-registered to the T2-weighted MRI scan. A learning curve was generated to determine the number of patients required for a stable machine-learning model. Patients were randomly stratified into 2 training sets and 1 test set. Two partial least-squares regression models were trained, each capable of predicting lumen and epithelium density. Predicted density values were calculated for each patient in the test dataset, mapped into the MRI space, and compared between regions confirmed as high-grade prostate cancer., Results: The learning-curve analysis showed that a stable fit was achieved with data from 10 patients. Maps indicated that regions of increased epithelium and decreased lumen density, generated from each independent model, corresponded with pathologist-annotated regions of high-grade cancer., Conclusions: We present a radio-pathomic approach to mapping prostate cancer. We find that the maps are useful for highlighting high-grade tumors. This technique may be relevant for dose-painting strategies in prostate radiation therapy., (Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objective: To evaluate the association between low back pain and bone marrow edema in lumbosacral transitional vertebra (LSTV) transverse processes, and to assess the prevalence of LSTV in a physically active population., Materials and Methods: Individuals with LSTV on coronal MRI studies were identified in a retrospective review by keyword search from PACS. In total, 140 cases were reviewed by two fellowship-trained musculoskeletal radiologists. Data on associated low back pain were collected from patient records at the time of the imaging., Results: Bone marrow edema was observed in 44% of the cases, but no correlation with low back pain was found. On coronal MRI, the prevalence of LSTV was 2.6%, with type II LSTV being the most common subtype., Conclusions: No correlation with bone marrow edema at the transverse processes of the LSTV and low back pain was observed. In our selected study population, the prevalence of LSTV was low.

Purpose: The standard treatment for organ-confined prostate cancer is surgery or radiation, and locally advanced prostate cancer is typically treated with radiotherapy alone or in combination with androgen deprivation therapy. Here, we investigated whether Stat5a/b participates in regulation of double-strand DNA break repair in prostate cancer, and whether Stat5 inhibition may provide a novel strategy to sensitize prostate cancer to radiotherapy. Experimental Design: Stat5a/b regulation of DNA repair in prostate cancer was evaluated by comet and clonogenic survival assays, followed by assays specific to homologous recombination (HR) DNA repair and nonhomologous end joining (NHEJ) DNA repair. For HR DNA repair, Stat5a/b regulation of Rad51 and the mechanisms underlying the regulation were investigated in prostate cancer cells, xenograft tumors, and patient-derived prostate cancers ex vivo in 3D explant cultures. Stat5a/b induction of Rad51 and HR DNA repair and responsiveness to radiation were evaluated in vivo in mice bearing prostate cancer xenograft tumors. Results: Stat5a/b is critical for Rad51 expression in prostate cancer via Jak2-dependent mechanisms by inducing Rad51 mRNA levels. Consistent with this, genetic knockdown of Stat5a/b suppressed HR DNA repair while not affecting NHEJ DNA repair. Pharmacologic Stat5a/b inhibition potently sensitized prostate cancer cell lines and prostate cancer tumors to radiation, while not inducing radiation sensitivity in the neighboring tissues. Conclusions: This work introduces a novel concept of a pivotal role of Jak2-Stat5a/b signaling for Rad51 expression and HR DNA repair in prostate cancer. Inhibition of Jak2-Stat5a/b signaling sensitizes prostate cancer to radiation and, therefore, may provide an adjuvant therapy for radiation to reduce radiation-induced damage to the neighboring tissues. Clin Cancer Res; 24(8); 1917-31. ©2018 AACR ., (©2018 American Association for Cancer Research.)

Evaluation of the subject-specific biomechanical effects of obesity on the progression of OA is challenging. The aim of this study was to create 3D MRI-based finite element models of the knee joints of seven obese subjects, who had developed OA at 4-year follow-up, and of seven normal weight subjects, who had not developed OA at 4-year follow-up, to test the sensitivity of cumulative maximum principal stresses in cartilage in quantitative risk evaluation of the initiation and progression of knee OA. Volumes of elements with cumulative stresses over 5 MPa in tibial cartilage were significantly (p < 0.05) larger in obese subjects as compared to normal weight subjects. Locations of high peak cumulative stresses at the baseline in most of the obese subjects showed a good agreement with the locations of the cartilage loss and MRI scoring at follow-up. Simulated weight loss (to body mass index 24 kg/m 2 ) in obese subjects led to significant reduction of the highest cumulative stresses in tibial and femoral cartilages. The modeling results suggest that an analysis of cumulative stresses could be used to evaluate subject-specific effects of obesity and weight loss on cartilage responses and potential risks for the progression of knee OA.

Multiparametric magnetic resonance imaging (MP-MRI), including diffusion-weighted imaging, is commonly used to diagnose prostate cancer. This radiology-pathology study correlates prostate cancer grade and morphology with common b -value combinations for calculating apparent diffusion coefficient (ADC). Thirty-nine patients undergoing radical prostatectomy were recruited for MP-MRI prior to surgery. Diffusion imaging was collected with seven b -values, and ADC was calculated. Excised prostates were sliced in the same orientation as the MRI using 3-D printed slicing jigs. Whole-mount slides were digitized and annotated by a pathologist. Annotated samples were aligned to the MRI, and ADC values were extracted from annotated peripheral zone (PZ) regions. A receiver operating characteristic (ROC) analysis was performed to determine accuracy of tissue type discrimination and optimal ADC b -value combination. ADC significantly discriminates Gleason (G) G4-5 cancer from G3 and other prostate tissue types. The optimal b -values for discriminating high from low-grade and noncancerous tissue in the PZ are 50 and 2000, followed closely by 100 to 2000 and 0 to 2000. Optimal ADC cut-offs are presented for dichotomized discrimination of tissue types according to each b -value combination. Selection of b -values affects the sensitivity and specificity of ADC for discrimination of prostate cancer.

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Mechanistic studies of deregulated ERG in prostate cancer and other cancers continue to enhance its role in cancer biology and its utility as a biomarker and therapeutic target. Here, we show that ERG, through its physical interaction with androgen receptor, induces AR aggregation and endoplasmic reticulum stress in the prostate glands of ERG transgenic mice. Histomorphological alterations and the expression of ER stress sensors Atf6, Ire1α, Perk, their downstream effectors Grp78/BiP and eIF2α in ERG transgenic mouse prostate glands indicate the presence of chronic ER stress. Transient activation of apoptotic cell death during early age correlated well with the differential regulation of ER stress sensors, in particular Perk. Epithelial cells derived from ERG transgenic mouse prostates have increased prostasphere formation with resistance to radiation induced cell death. Continued activation of cell survival factors, Atf6 and Ire1α during chronic ER stress due to presence of ERG in prostate epithelium induces survival pathways and provides a selection pressure in the continuum of ERG dependent neoplastic process. These novel insights will enhance the understanding of the mechanistic functions of ERG in prostate tumor biology and towards development of early targeted therapeutic strategies for prostate cancer.

Despite aggressive treatment for localized cancer, prostate cancer (PC) remains a leading cause of cancer-related death for American men due to a subset of patients progressing to lethal and incurable metastatic castrate-resistant prostate cancer (CRPC). Organ-confined PC is treated by surgery or radiation with or without androgen deprivation therapy (ADT), while options for locally advanced and disseminated PC include radiation combined with ADT, or systemic treatments including chemotherapy. Progression to CRPC results from failure of ADT, which targets the androgen receptor (AR) signaling axis and inhibits AR-driven proliferation and survival pathways. The exact mechanisms underlying the transition from androgen-dependent PC to CRPC remain incompletely understood. Reactivation of AR has been shown to occur in CRPC despite depletion of circulating androgens by ADT. At the same time, the presence of AR-negative cell populations in CRPC has also been identified. While AR signaling has been proposed as the primary driver of CRPC, AR-independent signaling pathways may represent additional mechanisms underlying CRPC progression. Identification of new therapeutic strategies to target both AR-positive and AR-negative PC cell populations and, thereby, AR-driven as well as non-AR-driven PC cell growth and survival mechanisms would provide a two-pronged approach to eliminate CRPC cells with potential for synthetic lethality. In this review, we provide an overview of AR-dependent and AR-independent molecular mechanisms which drive CRPC, with special emphasis on the role of the Jak2-Stat5a/b signaling pathway in promoting castrate-resistant growth of PC through both AR-dependent and AR-independent mechanisms.

The αvβ3 integrin is known to be highly upregulated during cancer progression and promotes a migratory and metastatic phenotype in many types of tumors. We hypothesized that the αvβ3 integrin is transferred through exosomes and, upon transfer, has the ability to support functional aberrations in recipient cells. Here, for the first time, it is demonstrated that αvβ3 is present in exosomes released from metastatic PC3 and CWR22Pc prostate cancer cells. Exosomal β3 is transferred as a protein from donor to nontumorigenic and tumorigenic cells as β3 protein or mRNA levels remain unaffected upon transcription or translation inhibition in recipient cells. Furthermore, it is shown that upon exosome uptake, de novo expression of an αvβ3 increases adhesion and migration of recipient cells on an αvβ3 ligand, vitronectin. To evaluate the relevance of these findings, exosomes were purified from the blood of TRAMP mice carrying tumors where the expression of αvβ3 is found higher than in exosomes from wild-type mice. In addition, it is demonstrated that αvβ3 is coexpressed with synaptophysin, a biomarker for aggressive neuroendocrine prostate cancer., Implications: Overall this study reveals that the αvβ3 integrin is transferred from tumorigenic to nontumorigenic cells via exosomes, and its de novo expression in recipient cells promotes cell migration on its ligand. The increased expression of αvβ3 in exosomes from mice bearing tumors points to its clinical relevance and potential use as a biomarker. Mol Cancer Res; 14(11); 1136-46. ©2016 AACR., Competing Interests: of Potential Conflicts of Interest The authors declare that they have no conflicts of interest., (©2016 American Association for Cancer Research.)

Objectives: To investigate the association between distal clavicular osteolysis (DCO) and bench pressing intensity., Methods: From a retrospective review of MRI shoulder reports of individuals between 20 and 40 years of age, 262 male patients with DCO and 227 age-matched male patients without DCO were selected. All patients had completed a bench pressing questionnaire. The patients' bench pressing frequency (times per week), duration (years of bench pressing), bench pressing weight (maximum bench pressing weight with one repetition = 1RM) and the ratio of bench pressing weight to body weight were compared between both groups using Chi-square and Mann-Whitney tests., Results: The results showed that 56 % (146/262) of patients with DCO were high-intensity bench pressers (1RM more than 1.5 times the body weight) compared to 6 % (14/227) in patients without DCO. High-intensity bench pressing was a risk factor for DCO (OR = 19; 95 %CI = 11-35; p < 0.001). Low-intensity bench pressing (1RM less than 1.5 times the body weight) was not a risk factor for DCO (OR = 0.6; 95 % CI = 0.4-0.8). High frequency (>1×/week) and duration (>5 years) of bench pressing were risk factors. In bench pressers who suffered from DCO, the mean 1RM was 283 lbs (±SD 57) compared to 209 lbs (±SD 60) in bench pressers not affected by DCO (p < 0.001, Mann-Whitney)., Conclusions: High-intensity, but not low-intensity bench pressing is a risk factor for DCO.

Trauma and the mechanical strain of high-energy activity predispose athletes to pelvic injuries. Magnetic resonance imaging remains the primary modality for diagnosing these conditions, but ultrasonography-guided interventions are important in the management of core muscle, hip, and other pelvic conditions. This article reviews ultrasonography-guided interventions for injuries at the core, including the pelvis and hips. It reviews common injuries, procedure optimization, medication preparation, clinical evidence behind injections, tenotomy, and platelet-rich plasma. These interventions are especially important in athletes, because ultrasonography-guided procedures are often undertaken early in the treatment process, paralleling conservative rehabilitation to facilitate a faster return to play., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Aim: To evaluate the prevalence of cervical facet oedema in patients referred for magnetic resonance imaging (MRI) to investigate neck pain and/or radiculopathy, and to investigate whether there is a correlation between the presence of oedema and patients' symptoms., Materials and Methods: A retrospective report review of 1885 patients undergoing cervical spine MRI between July 2008 and June 2015 was performed. Exclusion criteria included acute trauma, surgery, neoplastic disease, or infection in the cervical spine. One hundred and seventy-three MRI studies with cervical facet oedema were evaluated by each of the two radiologists. In these patients, the grade of bone marrow oedema (BMO) and corresponding neuroforaminal narrowing at the cervical facets was assessed. Correlation with symptoms was performed based on pre-MRI questionnaire., Results: The prevalence of cervical facet oedema was 9%; the most commonly affected levels were C3-4, C4-5, and C2-3. A total of 202 cervical facets were evaluated: mild BMO was seen in 35%, moderate in 41%, and severe in 24% of cases. Surrounding soft-tissue oedema was observed in 36%, 69%, and 92% of the BMO grades, respectively. The correlations between unilateral radiculopathy and ipsilateral facet BMO grades were 79%, 83%, and 73% (chi-square, p<0.001), respectively. Furthermore, neuroforaminal narrowing on the corresponding level was found in 35%, 38%, and 11% of cases, respectively. At follow-up imaging, facet oedema was most likely to remain unchanged or to decrease., Conclusion: The prevalence of cervical facet oedema is 9%. Cervical facet oedema is associated with ipsilateral radiculopathy. Neuroforaminal narrowing, however, is not associated with facet oedema., (Copyright © 2016 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.)

Bone marrow lesions observed in magnetic resonance imaging (MRI) have been recognized as a source of knee pain. Subchondroplasty was developed to treat these lesions with a percutaneous injection of calcium phosphate bone substitute into the bone. As subchondroplasty may potentially become a more common procedure in the treatment of knee osteoarthritis, it is important for radiologists to recognize the typical MRI findings and not to confuse them with other pathology. Here we report the MRI findings for two patients following subchondroplasty., (Copyright © 2015 Elsevier Inc. All rights reserved.)