Development and Optimization of a Subtraction-Normalized Immunocyte Profiling Signature for Prostate Cancer Active Surveillance Risk Stratification.

PURPOSE: Less invasive decision support tools are desperately needed to identify occult high-risk disease in men with prostate cancer (PCa) on active surveillance (AS). For a variety of reasons, many men on AS with low- or intermediate-risk disease forgo the necessary repeat surveillance biopsies needed to identify potentially higher-risk PCa. Here, we describe the development of a blood-based immunocyte transcriptomic signature to identify men harboring occult aggressive PCa. We then validate it on a biopsy-positive population with the goal of identifying men who should not be on AS and confirm those men with indolent disease who can safely remain on AS. This model uses subtraction-normalized immunocyte transcriptomic profiles to risk-stratify men with PCa who could be candidates for AS. MATERIALS AND METHODS: Men were eligible for enrollment in the study if they were determined by their physician to have a risk profile that warranted prostate biopsy. Both training (n = 1017) and validation cohort (n = 1198) populations had blood samples drawn coincident to their prostate biopsy. Purified CD2+ and CD14+ immune cells were obtained from peripheral blood mononuclear cells, and RNA was extracted and sequenced. To avoid overfitting and unnecessary complexity, a regularized regression model was built on the training cohort to predict PCa aggressiveness based on the National Comprehensive Cancer Network PCa guidelines. This model was then validated on an independent cohort of biopsy-positive men only, using National Comprehensive Cancer Network unfavorable intermediate risk and worse as an aggressiveness outcome, identifying patients who were not appropriate for AS. RESULTS: The best final model for the AS setting was obtained by combining an immunocyte transcriptomic profile based on 2 cell types with PSA density and age, reaching an AUC of 0.73 (95% CI: 0.69-0.77). The model significantly outperforms (P < .001) PSA density as a biomarker, which has an AUC of 0.69 (95% CI: 0.65-0.73). This model yields an individualized patient risk score with 90% negative predictive value and 50% positive predictive value. CONCLUSIONS: While further validation in an intended-use cohort is needed, the immunocyte transcriptomic model offers a promising tool for risk stratification of individual patients who are being considered for AS.

Quality rectal hydrogel placement allows for gel-enabled dose-escalated EBRT (GEDE-EBRT) without rectal interference in prostate cancer.

Multiple trials have shown that dose-escalation of radiation for prostate cancer provides a biochemical progression-free survival benefit (bPFS); however, rectal constraints are often limiting. In this dosimetric study, we hypothesized that a well-placed rectal hydrogel (RH) would permit improved dose-escalation and target coverage. We selected patients with good-quality RH and created plans with and without RH, prescribing 70 Gy in 28 fractions to the prostate and proximal seminal vesicles (PSV), and a peripheral zone (PZ) boost to 84 Gy, 98 Gy, or 112 Gy. We then compared plans with and without RH, prescribing a 112 Gy boost to 1 to 2 cm simulated dominant intraprostatic lesions (DIL). In the 18 plans created with a PZ boost, the PTV_boost D95% was higher in RH plans compared to non-RH plans (median 98.5 Gy vs 75.53 Gy, p < 0.01). The PSV planning target volume (PTV_PSV) D95% was also marginally higher with RH (71.87 Gy vs 71.04 Gy, p < 0.01). All rectal metrics were improved with RH. For the 32 plans created for simulated DILs treated to 112 Gy, the PTV_boost coverage (median D95% 112.48 Gy vs 102.63 Gy, p < 0.01) and rectal metrics were improved with RH. Four non-RH plans with at least a 4 mm rectal-PTV_boost gap achieved D95% > 98% of the prescription dose for the PTV_boost. Our study showed that placement of a high-quality RH allowed for GEDE-EBRT up to 112 Gy in 28 fractions (EQD2 160 Gy with α/ß = 2.5). This concept should be tested prospectively, particularly to assess for increases in nonrectal toxicities.

A Comparison of Magnetic Resonance Imaging and SPECT-CT Imaging in Complex Spine Pathology: Does SPECT-CT Provide Additional Diagnostic Information Over Magnetic Resonance Imaging?

STUDY DESIGN: Retrospective cohort study. OBJECTIVE: Magnetic Resonance Imaging (MRI) is often regarded as the gold standard for spinal pathology, as it provides good structural visualisation. SPECT-CT, however, provides combined structural and functional information. There is a paucity of literature comparing SPECT-CT with MRI in the spine. Our aim was to determine whether SPECT-CT provides additional information to MRI in individuals with complex spinal pathology, including deformity, which altered management. METHODS: We conducted a retrospective review of all individuals seen at our tertiary spinal unit that were investigated with both MRI and SPECT-CT of the spine between 2007-2020. We reviewed imaging reports, and collated diagnoses, surgical treatment and the relative contributions of MRI and SPECT-CT to management decisions. RESULTS: 104 individuals identified, with a mean age of 30 years (89 females and 15 males). Diagnostic categories were adolescent, adult, and congenital deformity, degenerative pathology, and miscellaneous pathology. MRI returned positive findings in 58 (55.8%), and SPECT-CT in 41 (39.4%) cases. SPECT-CT identified 10 cases of facet joint degeneration, 5 of increased uptake around metalwork suggestive of loosening, 1 pseudoarthrosis, 1 partial failure of fusion and 1 osteoid osteoma which were not reported on MRI, all in individuals who had previously undergone spinal instrumentation. Despite this, SPECT-CT only altered management for 6 individuals (5.8%). CONCLUSIONS: MRI is less useful in the setting of previous instrumentation due to metal artefact. Where MRI is inconclusive, particularly in individuals with previous spinal instrumentation, SPECT-CT may provide a diagnosis, but is not recommended as primary imaging.

Implication of the Gut Microbiome and Microbial-Derived Metabolites in Immune-Related Adverse Events: Emergence of Novel Biomarkers for Cancer Immunotherapy.

Immune checkpoint inhibitors (ICIs) have changed how we think about tumor management. Combinations of anti-programmed death ligand-1 (PD-L1) immunotherapy have become the standard of care in many advanced-stage cancers, including as a first-line therapy. Aside from improved anti-tumor immunity, the mechanism of action of immune checkpoint inhibitors (ICIs) exposes a new toxicity profile known as immune-related adverse effects (irAEs). This novel toxicity can damage any organ, but the skin, digestive and endocrine systems are the most frequently afflicted. Most ICI-attributed toxicity symptoms are mild, but some are severe and necessitate multidisciplinary side effect management. Obtaining knowledge on the various forms of immune-related toxicities and swiftly changing treatment techniques to lower the probability of experiencing severe irAEs has become a priority in oncological care. In recent years, there has been a growing understanding of an intriguing link between the gut microbiome and ICI outcomes. Multiple studies have demonstrated a connection between microbial metagenomic and metatranscriptomic patterns and ICI efficacy in malignant melanoma, lung and colorectal cancer. The immunomodulatory effect of the gut microbiome can have a real effect on the biological background of irAEs as well. Furthermore, specific microbial signatures and metabolites might be associated with the onset and severity of toxicity symptoms. By identifying these biological factors, novel biomarkers can be used in clinical practice to predict and manage potential irAEs. This comprehensive review aims to summarize the clinical aspects and biological background of ICI-related irAEs and their potential association with the gut microbiome and metabolome. We aim to explore the current state of knowledge on the most important and reliable irAE-related biomarkers of microbial origin and discuss the intriguing connection between ICI efficacy and toxicity.

Diaphragmatic paralysis post COVID-19 treated with robot-assisted plication reinforced with acellular dermal matrix: a report of two cases.

Coronavirus disease 2019 (COVID-19) continues to be a disease of global importance, with an increasing array of sequelae attributed to infection by the severe acute respiratory syndrome coronavirus-2. One such complication that has been rarely documented thus far is diaphragmatic dysfunction. Here, we report the cases of 2 individuals who developed diaphragmatic paralysis post COVID-19, which failed to respond to conservative management. Both patients proceeded to undergo robot-assisted thoracoscopic plication of the diaphragm reinforced with a bovine acellular dermal matrix. In both cases, there was significant improvement in symptomatology, namely dyspnoea and fatigue. We conclude that robot-assisted diaphragmatic plication should be considered for the treatment of refractory diaphragmatic paralysis post COVID-19.

Successful Closure of Post-pneumonectomy Bronchopleural Fistula With Suture Repair Reinforced With Porcine Acellular Dermal Matrix (Permacol) and Hydrogel Sealant (Progel): A Case Report.

Bronchopleural fistula (BPF) is a feared and potentially life-threatening complication of pneumonectomy. Clinical features such as a productive cough and subcutaneous emphysema raise suspicion of BPF with CT imaging and bronchoscopy providing a definitive diagnosis. In light of the significant morbidity and mortality associated with the condition, a significant proportion of cases necessitate surgical repair of the bronchial stump. Currently, there is no consensus on optimal surgical strategy. Traditionally, various vascularised tissue flaps, including pericardial fat pad, omentum, and muscle, have been used to buttress the repaired stump, with varying success rates. In light of this, novel approaches have been devised with the aim of achieving more consistent surgical outcomes. In this case report, we describe a novel approach to reinforcing the suture repair using porcine dermal collagen matrix (Permacol, Medtronic, Minneapolis, MN) and hydrogel sealant (Progel, BD, Franklin Lakes, NJ) to achieve successful closure of a BPF in an adult male patient following pneumonectomy for squamous cell carcinoma. The use of porcine dermal collagen matrix covered with hydrogel sealant is a viable alternative to traditional BPF closure strategies and can achieve good patient outcomes. This technique has several benefits including cost-effectiveness and sparing of native tissues, and it is technically straightforward. Further studies are required to compare the clinical outcomes of this and other novel techniques with traditional BPF closure approaches.

Serotonin transporter binding in major depressive disorder: impact of serotonin system anatomy.

Serotonin transporter (5-HTT) binding deficits are reported in major depressive disorder (MDD). However, most studies have not considered serotonin system anatomy when parcellating brain regions of interest (ROIs). We now investigate 5-HTT binding in MDD in two novel ways: (1) use of a 5-HTT tract-based analysis examining binding along serotonergic axons; and (2) using the Copenhagen University Hospital Neurobiology Research Unit (NRU) 5-HT Atlas, based on brain-wide binding patterns of multiple serotonin receptor types. [11C]DASB 5-HTT PET scans were obtained in 60 unmedicated participants with MDD in a current depressive episode and 31 healthy volunteers (HVs). Binding potential (BPP) was quantified with empirical Bayesian estimation in graphical analysis (EBEGA). Within the [11C]DASB tract, the MDD group showed significantly lower BPP compared with HVs (p = 0.02). This BPP diagnosis difference also significantly varied by tract location (p = 0.02), with the strongest MDD binding deficit most proximal to brainstem raphe nuclei. NRU 5-HT Atlas ROIs showed a BPP diagnosis difference that varied by region (p < 0.001). BPP was lower in MDD in 3/10 regions (p-values < 0.05). Neither [11C]DASB tract or NRU 5-HT Atlas BPP correlated with depression severity, suicidal ideation, suicide attempt history, or antidepressant medication exposure. Future studies are needed to determine the causes of this deficit in 5-HTT binding being more pronounced in proximal axon segments and in only a subset of ROIs for the pathogenesis of MDD. Such regional specificity may have implications for targeting antidepressant treatment, and may extend to other serotonin-related disorders.

Rectal sparing in prostate radiotherapy with combination-brachytherapy and hydrogel spacer.

BACKGROUND: Though some techniques that facilitate rectal sparing such as brachytherapy and intensity modulated radiotherapy (IMRT) have been examined in detail, technical aspects of hydrogel spacer (HS) have been studied less exhaustively. We examined HS quality metrics and approaches to placement for superior dosimetric outcomes. MATERIALS AND METHODS: A single site retrospective review of radiation plans was conducted for patients who received combination-brachytherapy (CBT) with 90 Gy low-dose-rate implant followed by external beam radiotherapy (45 Gy/25 fractions) with operating room (OR) placed HS (2017-2021). A randomly selected set of patients that received CBT without HS over the same time period was used for comparison. Dosimetric outcomes included D1cc and D5% rectum. Dose gradients were quantified. Student's t-test was used for statistical comparisons. RESULTS: Sixty patients (30 with and 30 without HS) who received CBT for prostate cancer were examined. Those with HS had lower mean D1cc [65.31 Gy (SD = 13.53)] and D5% [53.20 Gy (SD = 10.18)] compared to those treated without HS [91.67 Gy (SD = 8.31) and 75.00 Gy (SD = 8.45), respectively, p < 0.001]. Patients with superior HS (average thickness ≥1 cm; n = 12) had lower mean D1cc [58.49 Gy (SD = 13.25, p = 0.026)] and D5% [48.69 Gy (SD = 9.85, p = 0.049)] than those with thinner HS. When dose gradients were considered, HS spanning the interface between the prostate and perirectal tissues to a thickness ≥1 cm can reduce rectal maximum dose to 50-60 Gy. CONCLUSIONS: Through effective use of CBT and HS, extreme rectal dose restriction is possible. The goal for HS placement should be thickness ≥1 cm from base to apex.

Impact of Decipher Biopsy testing on clinical outcomes in localized prostate cancer in a prospective statewide collaborative.

BACKGROUND: Decipher Biopsy is a commercially available gene expression classifier used in risk stratification of newly diagnosed prostate cancer (PCa). Currently, there are no prospective data evaluating its clinical utility. We seek to assess the clinical utility of Decipher Biopsy in localized PCa patients. METHODS: A multi-institutional study of 855 men who underwent Decipher Biopsy testing between February 2015 and October 2019. All patients were tracked through the prospective Michigan Urological Surgery Improvement Collaborative and linked to the Decipher Genomics Resource Information Database (GRID®; NCT02609269). Patient matching was performed by an independent third-party (ArborMetrix Inc.) using two or more unique identifiers. Cumulative incidence curves for time to treatment (TTT) and time to failure (TTF) were constructed using Kaplan-Meier estimates. Multivariable Cox proportional hazard models were used to evaluate the independent association of high-risk Decipher scores with the conversion from AS to radical therapy and treatment failure (biochemical failure or receipt of salvage therapy). RESULTS AND LIMITATIONS: Eight hundred fifty-five patients underwent Decipher Biopsy testing during the study period. Of the 855 men, 264 proceeded to AS (31%), and 454 (53%) received radical therapy. In men electing AS, after adjusting for NCCN risk group, age, PSA, prostate volume, body mass index, and percent positive cores, a high-risk Decipher score was independently associated with shorter TTT (HR 2.51, 95% CI 1.52-4.13 p < 0.001). Similarly, in patients that underwent radical therapy, a high-risk Decipher score was independently associated with TTF (HR 2.98, 95% CI 1.22-7.29, p = 0.01) on multivariable analysis. Follow-up time was a limitation. CONCLUSION: In a prospective statewide registry, high-risk Decipher Biopsy score was strongly and independently associated with conversion from AS to definitive treatment and treatment failure. These real-world data support the clinical utility of Decipher Biopsy. An ongoing phase 3 randomized trial (NCT04396808) will provide level 1 evidence of the clinical impact of Decipher biopsy testing.

Synovial tissue from sites of joint pain in knee osteoarthritis patients exhibits a differential phenotype with distinct fibroblast subsets.

BACKGROUND: Synovial inflammation is associated with pain severity in patients with knee osteoarthritis (OA). The aim here was to determine in a population with knee OA, whether synovial tissue from areas associated with pain exhibited different synovial fibroblast subsets, compared to synovial tissue from sites not associated with pain. A further aim was to compare differences between early and end-stage disease synovial fibroblast subsets. METHODS: Patients with early knee OA (n = 29) and end-stage knee OA (n = 22) were recruited. Patient reported pain was recorded by questionnaire and using an anatomical knee pain map. Proton density fat suppressed MRI axial and sagittal sequences were analysed and scored for synovitis. Synovial tissue was obtained from the medial and lateral parapatellar and suprapatellar sites. Fibroblast single cell RNA sequencing was performed using Chromium 10X and analysed using Seurat. Transcriptomes were functionally characterised using Ingenuity Pathway Analysis and the effect of fibroblast secretome on neuronal growth assessed using rat DRGN. FINDINGS: Parapatellar synovitis was significantly associated with the pattern of patient-reported pain in knee OA patients. Synovial tissue from sites of patient-reported pain exhibited a differential transcriptomic phenotype, with distinct synovial fibroblast subsets in early OA and end-stage OA. Functional pathway analysis revealed that synovial tissue and fibroblast subsets from painful sites promoted fibrosis, inflammation and the growth and activity of neurons. The secretome of fibroblasts from early OA painful sites induced greater survival and neurite outgrowth in dissociated adult rodent dorsal root ganglion neurons. INTERPRETATION: Sites of patient-reported pain in knee OA exhibit a different synovial tissue phenotype and distinct synovial fibroblast subsets. Further interrogation of these fibroblast pathotypes will increase our understanding of the role of synovitis in OA joint pain and provide a rationale for the therapeutic targeting of fibroblast subsets to alleviate pain in patients. FUNDING: This study was funded by Versus Arthritis, UK (21530; 21812).

Prostate radiotherapy in the setting of bilateral hip prostheses: All commonly used photon-based radiation approaches are feasible.

The prevalence of hip prostheses is increasing. Prostate radiation delivery in the setting of hip prostheses is complicated by both imaging artifacts that interfere with volume delineation and dosimetric effects that must be addressed in the planning process. We hypothesized that with specialized planning, any photon-based definitive prostate radiotherapy approach may be utilized in patients with bilateral hip prostheses. Imaging data from sequential patients with prostate cancer and bilateral hip prostheses treated definitively with radiation were retrospectively reviewed. Bimodality imaging was used to define targets and organs at risk (OARs) along with specialized MRI sequences and/or orthopedic metal artifact reduction (OMAR) for MRI and CT artifact suppression, respectively. Multiple VMAT plans were generated for each set of patient images to include three fractionation schemes (conventional, hypofractionated, and SBRT), each with hip avoidance and with simulated normal hip. The ability to meet standard dose constraints was assessed for each plan type. Differences in target and OAR dosing between plans accounting for prosthetic hips via avoidance vs plans with simulated absence of prosthetic hip were also assessed. T-tests were used to compare dosimetric parameters. Ten patients with bilateral hip prostheses were identified, and 6 plans were created for each patient for a total of 60 radiation plans. Prosthetic hip avoidance did not result in failure to meet dose constraints for any patient. Hip avoidance resulted in minimal increases in high dose to the rectum and bladder (increases in mean V80%, V90%, and V95% ranged from 0.1% to 2.4%). Larger increases were seen at lower dose levels, with rectal V50% significantly increased in all three plan types with hip avoidance (conventional: 26.0% [standard deviation, SD 13.9] vs 16.9% [SD 10.2, p = 0.003]; hypofractionation: 26.4% [SD 13.3] vs 17.1% [SD 10.1, p = 0.002]; SBRT: 18.3% [SD 10.7] vs 10.5% [SD 6.9, p = 0.008]). Similarly, hip avoidance resulted in increases in bladder V50% to 31.7% (SD 16.8) vs 23.3% (SD 14.0, p = 0.001), 31.3% (SD 17.0) vs 23.3% (SD 13.8, p = 0.002), and 22.7% (SD 12.3) vs 16.5% (SD 12.6, p < 0.001) for conventional, hypofractionated, and SBRT plans, respectively. Hydrogel spacer resulted in reductions in rectal dose. For example, V70% for hip avoidance plans decreased with spacer presence to 8.3% (SD 6.7) vs 21.1% (SD 5.8, p = 0.021), 8.6% (SD 6.5) vs 21% (SD 5.7, p = 0.022), and 3.7% (SD 3.2) vs 15% (SD 8.2, p = 0.010) for conventional, hypofractionated, and SBRT plans, respectively. Any photon-based definitive prostate radiotherapy approach can be used with bimodality imaging for target and OAR definition and planning techniques to avoid dose attenuation effects of hip prostheses. Hydrogel spacer is a useful adjunct.

Proactive Consultation-Liaison Psychiatry: American Psychiatric Association Resource Document.

In 2019, the American Psychiatric Association Council on Consultation-Liaison (C-L) Psychiatry convened a work group to develop a resource document on proactive C-L psychiatry. A draft of this document was reviewed by the Council in July 2020, and a revised version was approved by this Council in September 2020. The accepted version was subsequently reviewed by the American Psychiatric Association Council on Health Care Systems and Financing in November 2020. The final version was approved by the Joint Reference Committee on November 24, 2020, and received approval for publication by the Board of Trustees on December 12, 2020. This resource document describes the historical context and modern trends that have given rise to the model of proactive C-L psychiatry. Styled as an inpatient corollary to outpatient collaborative care models, proactive C-L provides a framework of mental health care delivery in the general hospital designed to enhance mental health services to a broad range of patients. Its 4 elements include systematic screening for active mental health concerns, proactive interventions tailored to individual patients, team-based care delivery, and care integration with primary teams and services. Studies have found that proactive C-L psychiatry is associated with reduced hospital length of stay, enhanced psychiatric service utilization, reduced time to psychiatric consultation, and improved provider and nurse satisfaction. These favorable results encourage further studies that replicate and build upon these findings. Additional outcomes such as patient experience, health outcomes, and readmission rates deserve investigation. Further studies are also needed to examine a broader array of team compositions and the potential value of proactive C-L psychiatry to different hospital settings such as community hospitals, surgery, and critical care.

Can MRI be used as a safe and expedient option for calculating Spinal Instability Neoplastic Score for patients with metastatic spinal cord compression?

AIMS: The aim of this study was to assess the reliability of using MRI scans to calculate the Spinal Instability Neoplastic Score (SINS) in patients with metastatic spinal cord compression (MSCC). METHODS: A total of 100 patients were retrospectively included in the study. The SINS score was calculated from each patient's MRI and CT scans by two consultant musculoskeletal radiologists (reviewers 1 and 2) and one consultant spinal surgeon (reviewer 3). In order to avoid potential bias in the assessment, MRI scans were reviewed first. Bland-Altman analysis was used to identify the limits of agreement between the SINS scores from the MRI and CT scans for the three reviewers. RESULTS: The limit of agreement between the SINS score from the MRI and CT scans for the reviewers was -0.11 for reviewer 1 (95% CI 0.82 to -1.04), -0.12 for reviewer 2 (95% CI 1.24 to -1.48), and -0.37 for reviewer 3 (95% CI 2.35 to -3.09). The use of MRI tended to increase the score when compared with that using the CT scan. No patient having their score calculated from MRI scans would have been classified as stable rather than intermediate or unstable when calculated from CT scans, potentially leading to suboptimal care. CONCLUSION: We found that MRI scans can be used to calculate the SINS score reliably, compared with the score from CT scans. The main difference between the scores derived from MRI and CT was in defining the type of bony lesion. This could be made easier by knowing the site of the primary tumour when calculating the score, or by using inverted T1-volumetric interpolated breath-hold examination MRI to assess the bone more reliably, similar to using CT. Cite this article: Bone Joint J 2021;103-B(5):971-975.

Prospective monitoring of imaging guideline adherence by physicians in a surgical collaborative: comparison of statistical process control methods for detecting outlying performance.

BACKGROUND: Systematic, automated methods for monitoring physician performance are necessary if outlying behavior is to be detected promptly and acted on. In the Michigan Urological Surgery Improvement Collaborative (MUSIC), we evaluated several statistical process control (SPC) methods to determine the sensitivity and ease of interpretation for assessing adherence to imaging guidelines for patients with newly diagnosed prostate cancer. METHODS: Following dissemination of imaging guidelines within the Michigan Urological Surgery Improvement Collaborative (MUSIC) for men with newly diagnosed prostate cancer, MUSIC set a target of imaging < 10% of patients for which bone scan is not indicated. We compared four SPC methods using Monte Carlo simulation: p-chart, weighted binomial CUSUM, Bernoulli cumulative sum (CUSUM), and exponentially weighted moving average (EWMA). We simulated non-indicated bone scan rates ranging from 5.9% (within target) to 11.4% (above target) for a representative MUSIC practice. Sensitivity was determined using the average run length (ARL), the time taken to signal a change. We then plotted actual non-indicated bone scan rates for a representative MUSIC practice using each SPC method to qualitatively assess graphical interpretation. RESULTS: EWMA had the lowest ARL and was able to detect changes significantly earlier than the other SPC methodologies (p < 0.001). The p-chart had the highest ARL and thus detected changes slowest (p < 0.001). EWMA and p-charts were easier to interpret graphically than CUSUM methods due to their ability to display historical imaging rates. CONCLUSIONS: SPC methods can be used to provide informative and timely feedback regarding adherence to healthcare performance target rates in quality improvement collaboratives. We found the EWMA method most suited for detecting changes in imaging utilization.

The combination of local infiltration analgesia reagents increases their detrimental effect on human hip OA patient osteoblast viability and function.

The purpose was to evaluate the effect of Local infiltration analgesia (LIA) reagents in monotherapy and in combinations at clinical doses, on the viability and function of osteoblasts isolated from hip OA patients undergoing orthopaedic surgery. Human hip OA osteoblasts were exposed to LIA reagents including Bupivacaine, Lidocaine, Ropivacaine, Ketorolac and combinations with Adrenaline for 30 min. Osteoblast cellular viability and function was determined at 24 h and 7 days post-exposure. In conclusion, our data shows that LIA reagents, most notably Bupivacaine and its use in combination, are detrimental to human hip OA osteoblasts at concentrations advocated for clinical use.

Embolization of hemorrhagic renal angiomyolipoma complicated by arteriovenous shunting: A case report.

Arteriovenous shunting associated with angiomyolipoma is an unusual entity, which carries important implications to embolization approach. We present a distinctive case involving a 41-year-old woman who presented with retroperitoneal hemorrhage relating to renal angiomyolipoma. During angiography for urgent embolization, a complex vascular supply with arteriovenous shunting was encountered. Superselective embolization using alcohol or small particles is the standard approach to definitive treatment of symptomatic angiomyolipoma; however; their use is precluded in the setting of arteriovenous shunt hemodynamics. In this case, a 2-step approach was employed by which the initial hemorrhage was treated with proximal embolization using large gelatin foam and metallic coils. This resulted in decreased flow through the arteriovenous shunt, allowing the use high viscosity ethylene vinyl alcohol copolymer dissolved in dimethyl sulfoxide for definitive treatment.

Establishment of a Web-based System for Collection of Patient-reported Outcomes After Radical Prostatectomy in a Statewide Quality Improvement Collaborative.

OBJECTIVE: To report on the establishment of a unified, electronic patient-reported outcome (PRO) infrastructure and pilot results from the first 5 practices enrolled in the web-based collection system developed by the Michigan Urological Surgery Improvement Collaborative. MATERIALS AND METHODS: Eligible patients were those undergoing radical prostatectomy of 5 academic and community practices. PRO was obtained using a validated 21-item web-based questionnaire, regarding urinary function, erection function, and sexual interest and satisfaction. Data were collected preoperatively, at 3 months, and 6 months postoperatively. Patients were provided a link via email to complete the surveys. Perioperative and PRO data were analyzed as reports for individual patients and summary performance reports for individual surgeons. RESULTS: Among 773 eligible patients, 688 (89%) were enrolled preoperatively. Survey completion rate was 88%, 84%, and 90% preoperatively, at 3 months, and 6 months. Electronic completion rates preoperatively, at 3 months, and 6 months were 70%, 70%, and 68%, respectively. Mean urinary function scores were 18.3, 14.3, and 16.6 (good function ≥ 17), whereas mean erection scores were 18.7, 7.3, and 9.1 (good erection score ≥ 22) before surgery, at 3 months, and 6 months. Variation was noted for erectile function among the practices. CONCLUSION: Collection of electronic PRO via this unified, web-based format was successful and provided results that reflect expected recovery and identify opportunities for improvement. This will be extended to more practices statewide to improve outcomes after radical prostatectomy.

A Statewide Intervention Improves Appropriate Imaging in Localized Prostate Cancer.

PURPOSE: We implemented a statewide intervention to improve imaging utilization for the staging of patients with newly diagnosed prostate cancer. MATERIALS AND METHODS: MUSIC (Michigan Urological Surgery Improvement Collaborative) is a quality improvement collaborative comprising 42 diverse practices representing approximately 85% of the urologists in Michigan. MUSIC has developed imaging appropriateness criteria (prostate specific antigen greater than 20 ng/ml, Gleason score 7 or higher and clinical stage T3 or higher) which minimize unnecessary imaging with bone scan and computerized tomography. After baseline rates of radiographic staging were established in 2012 and 2013, we used multidimensional interventions to deploy these criteria in 2014. Imaging utilization was then remeasured in 2015 to evaluate for changes in practice patterns. RESULTS: A total of 10,554 newly diagnosed patients with prostate cancer were entered into the MUSIC registry from January 1, 2012 through December 31, 2013 and January 1, 2015 through December 31, 2015. Of these patients 7,442 (79%) and 7,312 (78%) met our criteria to avoid bone scan and computerized tomography imaging, respectively. The use of bone scan imaging when not indicated decreased from 11.0% at baseline to 6.5% after interventions (p <0.0001). The use of computerized tomography when not indicated decreased from 14.7% at baseline to 7.7% after interventions (p <0.0001). Variability among practices decreased substantially after the interventions as well. The use of recommended imaging remained stable during these periods. CONCLUSIONS: An intervention aimed at appropriate use of imaging was associated with decreased use of bone scans and computerized tomography among men at low risk for metastases.