Greater Disease Research Articles

A Single Institution Experience in the Management of Localized Neuroendocrine Carcinoma of the Bladder

BackgroundNeuroendocrine carcinoma of the bladder (NEC-bladder) is a rare disease with poor outcomes and variable treatment approaches. Materials and MethodsPatients with localized NEC-bladder treated with surgery or radiation between 2001-2021 were retrospectively identified. Rates of pathologic complete response (pCR) and downstaging were evaluated following NAC in surgically-treated patients. Progression-free survival (PFS) and overall survival (OS) were analyzed with univariable (log-rank) and multivariable (MVA; Cox regression) methods. ResultsSixty-five patients were identified having a median age of 73. The tumor histology distribution was small cell (64.6%) or urothelial with NE differentiation (35.4%). Most patients (69.2%) received NAC. Patients received local therapy by surgery (78.5%) or chemoradiation (21.5%). The majority (62.7%) of surgical patients had ≥ pT2 with 37.3% having nodal involvement (pN+). The pCR and downstaging rates were 21.6% and 35.1%, respectively. At a median follow-up of 60 months (m), the median PFS and OS were 16.4m and 25.9m, respectively. NAC improved PFS (p=0.04) and downstaging improved PFS (p=0.012) and OS (p<0.001). Patients receiving NAC with ypN0 vs. ypN+ had median OS of 69.9m vs 15.3m, respectively (p<0.001). MVA identified receipt of NAC and pN as predictors of PFS; pN was predictive of OS. No differences in PFS or OS were seen between histology of primary tumor. The brain metastasis rate was 10.8% with all patients having small cell histology. ConclusionsOptimized therapy in NEC-bladder includes NAC followed by local consolidation. Ascertainment of ypN0 is associated with long term survival, while pN+ remains associated with poor outcomes.

Definitive single fraction spine stereotactic radiosurgery for metastatic sarcoma: Simultaneous integrated boost is associated with high tumor control and low vertebral fracture risk

IntroductionSarcoma spinal metastases (SSM) are particularly difficult to manage given their poor response rates to chemotherapy and inherent radioresistance. We evaluated outcomes in a cohort of patients with SSM uniformly treated using single-fraction simultaneous-integrated-boost (SIB) spine stereotactic radiosurgery (SSRS). Materials and MethodsA retrospective review was conducted at a single tertiary institution treated with SSRS for SSM between April 2007-April 2023. 16–24 Gy was delivered to the GTV and 16 Gy uniformly to the CTV. Kaplan-Meier analysis was conducted to assess time to progression of disease (PD) with proportionate hazards modelling used to determine hazard ratios (HR) and respective 95 % confidence intervals (CI). Results70 patients with 100 lesions underwent SSRS for SSM. Median follow-up was 19.3 months (IQR 7.7–27.8). Median age was 55 years (IQR42-63). Median GTV and CTVs were 14.5 cm3 (IQR 5–32) and 52.7 cm3 (IQR 29.5–87.5) respectively. Median GTV prescription dose and biologically equivalent dose (BED) [α/β = 10] was 24 Gy and 81.6 Gy respectively. 85 lesions received 24 Gy to the GTV. 27 % of patients had Bilsky 1b or greater disease. 16 of 100 lesions recurred representing a crude local failure rate of 16 % with a median time to failure of 10.4 months (IQR 5.7–18) in cases which failed locally. 1-year actuarial local control (LC) was 89 %. Median overall survival (OS) was 15.3 months (IQR 7.7–25) from SSRS. Every 1 Gy increase in GTV absolute minimum dose (DMin) across the range (5.8–25 Gy) was associated with a reduced risk of local failure (HR = 0.871 [95 % CI 0.782–0.97], p = 0.009). 9 % of patients developed vertebral compression fractures at a median of 13 months post SSRS (IQR 7–25). ConclusionThis study represents one of the most homogenously treated and the largest cohorts of patients with SSM treated with single-fraction SSRS. Despite inherent radioresistance, SSRS confers durable and high rates of local control in SSM without unexpected long-term toxicity rates.

A Facility-Level Analysis of Nursing Home Compare's Five-Star Rating and Maryland's Family Satisfaction with Care Survey.

Nursing facilities care for individuals with cognitive and/or physical disabilities. Poor quality is associated with greater disease and mortality. Quality comprises many factors and different stakeholders value different factors. This study aimed to compare two care quality frameworks, one based on observable factors and one on family satisfaction. We merged publicly available 2021 Maryland nursing facility data. The Maryland Health Care Commission surveys long-term care residents' family satisfaction across seven domains. Centers for Medicare and Medicaid Services' (CMS) 5-star ratings aggregate inspections, staffing, and quality measures. We used univariate and bivariate statistics to compare the frameworks. The data set included 220 facilities and 4,610 survey respondents. The average facility rating was 7.70/10 and overall 77% of respondents would recommend the facility. Eighty-six percent of respondents from 5-star facilities, 79% from 4-star facilities, and 76% from 3-star facilities would recommend the facility compared to 65% from 1-star facilities (p < .001, p < .01, and p < .05, respectively). Four or 5-star facilities received significantly higher ratings (8.33, p < .001; 7.75, p < .05, respectively) than 1-star facilities (7.07). Our results corroborated earlier findings of strong associations between CMS ratings and satisfaction at the extremes of the 5-star system. These associations are inconsistent across family-reported domains. This suggests overlap between the frameworks. CMS ratings address care quality; family satisfaction measures quality of life and care quality. High satisfaction is associated with high care quality and quality of life; lower satisfaction is associated with lower care quality.

Dosimetric Analysis of Local Failure Outcomes and Vertebral Compression Fracture Risk in Single-Fraction Spine Stereotactic Radiosurgery for Metastatic Sarcoma

Sarcoma spinal metastases (SSM) are particularly difficult to manage given their poor response rates to chemotherapy and their inherent radioresistance. We sought to analyze dosimetric parameters impacting local failure and vertebral compression fracture outcomes in a homogenously treated cohort of patients with SSM treated with single-fraction spine stereotactic radiosurgery (SSRS). A retrospective review was conducted on a cohort of patients with SSM treated with definitive SSRS at a single tertiary institution. 16-24 Gy was delivered to the GTV and 16 Gy uniformly to the CTV. Kaplan-Meier analysis was conducted to assess time to local failure (LF). The log-rank test was utilized to examine group differences. Patients were censored at time of last follow-up or death. Cox proportionate hazards modeling was used to determine hazard ratios (HR) and their respective 95% confidence intervals (CI). A total of 66 patients with 96 lesions underwent SSRS for SSM. Median follow-up was 17 months (IQR 8-28). Median age was 55 years (IQR 41-63). The most common histological subtype was leiomyosarcoma (41%) followed by liposarcoma (9%). 81 lesions received 24 Gy to the GTV, 12 received 18 Gy and 3 received 16 Gy. Median GTV and CTV volume was 13.6cc (IQR 5-27) and 51.6cc (IQR 30-80) respectively. 27% of patients had Bilsky 1b or greater disease. 16 of 96 lesions demonstrated progression representing a crude local failure rate of 17% with median time to failure of 8 months (IQR 5-18). The 1-year actuarial progression free survival (PFS) was 89% with a median PFS of 13 months (IQR 16-63). Median overall survival (OS) was 15 months (IQR 8-28) from SSRS. 8% of patients developed vertebral compression fractures at a median of 13 months post SSRS (IQR 7-25). Every 1 Gy increase in GTV minimum dose (DMin) across the range (5.8-25cc) was associated with a reduced risk of local failure (HR = 0.875 [95% CI 0.787-0.974], p = 0.01). Stratifying thresholds for GTV DMin, a local control benefit was seen as low as 12 Gy and higher (HR = 0.329 [95% CI 0.11-0.97, p = 0.044) with a significantly greater magnitude benefit seen at 14 Gy (HR = 0.267 [95% CI 0.09-0.77, p = 0.014) and above 15 Gy (HR = 0.091 [95% CI 0.03-0.41], p = 0.0018). There were no other queried variables besides GTV Dmin associated with local control including: GTV: volume, mean, Dmax, D90, CTV: volume, Dmin, Dmean, Dmax, or D90. There was an increased risk of VCF with increasing CTV DMean (HR = 2.4 [95% CI 1.4-4.1], p = 0.002) and CTV D90 (HR = 2.2 [95% CI 1.2-4.0], p = 0.01); however, no association with GTV parameters. This study represents one of the most homogenously treated and the largest cohorts of patients with sarcoma spinal metastases treated with single-fraction SSRS. Despite inherent radioresistance, SSRS confers durable and high rates of local control in SSM without unexpected long-term toxicity rates. Increasing GTV minimum dose is significantly associated with superior local control with no corresponding increased risk of VCF.

Plant growth stage and Phoma medicaginis inoculum concentration together determine severity of Phoma black stem and leaf spot and consequent phytoestrogen production in annual Medicago spp.

AbstractPhoma black stem and leaf spot disease (Phoma medicaginis) not only destroys annual Medicago spp. forage and seed yield but also reduces herbage quality by consequent phytoestrogen production that reduces ovulation of grazing animals. Two controlled environment studies evaluated the effects of plant developmental stage in annual Medicago rugosa ‘Paraponto’ and M. scutellata ‘Sava’ and different inoculum concentrations of P. medicaginis in M. littoralis ‘Harbinger’ and M. polymorpha ‘Serena’ on disease development and coumestrol production. Disease incidence and severity and coumestrol production were dependent on plant developmental stage, cultivar and inoculum level (all p ≤ 0.001). Disease was least in 4‐week‐old plants; highest coumestrol was in inoculated 10‐week‐old Sava (1353 mg/kg) and least coumestrol in uninoculated 4‐week‐old Paraponto (87 mg/kg); and there was a positive correlation of disease incidence/severity factors with coumestrol across cultivars and plant growth stages (p &lt; 0.001). Disease levels and coumestrol production were determined by inoculum concentration and cultivar (both p ≤ 0.001). Highest coumestrol was in Serena inoculated with 107 conidia/mL (265 mg/kg); lowest coumestrol was in uninoculated Harbinger (6 mg/kg); and there was a significant positive correlation of disease incidence/severity factors with coumestrol across cultivars and inoculum concentrations (p &lt; 0.001). These studies emphasize both the opportunity for farmers to better use annual Medicago spp. stands for grazing reproducing animals early in the growing season when both disease and coumestrol levels are lowest, and the need for heightened farmer vigilance at later growth stages with greater disease and consequent phytoestrogen risk for grazing animals.

MP55-04 THE PREOPERATIVE USE OF MICROUS TO DETECT EXTRAPROSTATIC EXTENSION OF PROSTATE CANCER: AN UPDATE OF A SINGLE INSTITUTIONAL PROSPECTIVE SERIES

You have accessJournal of UrologyCME1 Apr 2023MP55-04 THE PREOPERATIVE USE OF MICROUS TO DETECT EXTRAPROSTATIC EXTENSION OF PROSTATE CANCER: AN UPDATE OF A SINGLE INSTITUTIONAL PROSPECTIVE SERIES Vittorio Fasulo, Fabio De Carne, Edoardo Beatrici, Luca Disconzi, Nicola Frego, Pier Paolo Avolio, Marco Paciotti, Andrea Gobbo, Pietro Diana, Alessandro Uleri, Davide Maffei, Giuseppe Chiarelli, Paola Arena, Giuseppe Garofano, Alberto Saita, Rodolfo Hurle, Massimo Lazzeri, Nicolò Maria Buffi, Paolo Casale, and Giovanni Lughezzani Vittorio FasuloVittorio Fasulo More articles by this author , Fabio De CarneFabio De Carne More articles by this author , Edoardo BeatriciEdoardo Beatrici More articles by this author , Luca DisconziLuca Disconzi More articles by this author , Nicola FregoNicola Frego More articles by this author , Pier Paolo AvolioPier Paolo Avolio More articles by this author , Marco PaciottiMarco Paciotti More articles by this author , Andrea GobboAndrea Gobbo More articles by this author , Pietro DianaPietro Diana More articles by this author , Alessandro UleriAlessandro Uleri More articles by this author , Davide MaffeiDavide Maffei More articles by this author , Giuseppe ChiarelliGiuseppe Chiarelli More articles by this author , Paola ArenaPaola Arena More articles by this author , Giuseppe GarofanoGiuseppe Garofano More articles by this author , Alberto SaitaAlberto Saita More articles by this author , Rodolfo HurleRodolfo Hurle More articles by this author , Massimo LazzeriMassimo Lazzeri More articles by this author , Nicolò Maria BuffiNicolò Maria Buffi More articles by this author , Paolo CasalePaolo Casale More articles by this author , and Giovanni LughezzaniGiovanni Lughezzani More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003308.04AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Stratification of patients with localized prostate cancer (PCa) before robotic assisted radical prostatectomy (RARP) allows performing a tailor-made surgery, potentially providing a nerve-sparing procedure even in those patients with high-risk disease. Nowadays the accuracy of clinical parameters to determine extraprostatic extension (EPE) is moderate, so a new imaging tool capable of providing a more accurate assessment is in order. Our goal is to evaluate the added value of microUS in the preoperative prediction of EPE. METHODS: Our prospective single-institutional cohort study enrolled patients with diagnosis of PCa scheduled for RARP. We included patients with PSA<20 ng/mL, prostate volume<100 mL and a preoperative microUS investigation. MRI-derived features (curvilinear contact length [CCL], capsular bulging, visible extracapsular extension [ECE]), along with microUS features (such as the presence of hypoechoic halo and obliteration of the vesicle-prostatic angle) were tested as predictors of EPE. Multivariable logistic regression models were fitted to test the accuracy of clinical parameters (total PSA, ISUP biopsy and digital rectal examination [DRE]) plus microUS parameters for EPE prediction. RESULTS: Overall, 230 patients were recruited. All predictors were associated with non-organconfined disease (p<0.001). Histological findings showed that 131 (56.9%) and 99 (43.0%) had respectively a pT2 and a pT3 or greater disease. Individuals with only 1 predictor had a rate of non-organconfined PCa of 16.7% (OR 3.12), compared to 93.8% in those where 4 predictors were simultaneously observed (OR 75.0). At MLRM, the most significant risk factors for EPE were visible ECE (OR 3.23; p<0.004), positive DRE (OR 2.5;p=0.015), and PSA (OR 1.06; p=0.03). The AUC increased from 0.809 to 0.841 when considering the clinical model alone and the model including both clinical and microUS features respectively (Figure 1). The DeLong test for equality showed a significant difference between the two curves (p=0.04). CONCLUSIONS: Our results confirm that microUS may represent an accurate tool for the evaluation of non-organ confined PCa. Future studies should externally validate our findings and determine the impact of microUS in the outcomes of RARP. Source of Funding: None © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e764 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Vittorio Fasulo More articles by this author Fabio De Carne More articles by this author Edoardo Beatrici More articles by this author Luca Disconzi More articles by this author Nicola Frego More articles by this author Pier Paolo Avolio More articles by this author Marco Paciotti More articles by this author Andrea Gobbo More articles by this author Pietro Diana More articles by this author Alessandro Uleri More articles by this author Davide Maffei More articles by this author Giuseppe Chiarelli More articles by this author Paola Arena More articles by this author Giuseppe Garofano More articles by this author Alberto Saita More articles by this author Rodolfo Hurle More articles by this author Massimo Lazzeri More articles by this author Nicolò Maria Buffi More articles by this author Paolo Casale More articles by this author Giovanni Lughezzani More articles by this author Expand All Advertisement PDF downloadLoading ...

Assessment of Epstein-Barr virus, Candida albicans, and some periodontal pathogens in rheumatoid arthritis patients with periodontitis.

To comparatively investigate the periodontal results and microbial load in subgingival biofilm samples (SBS) in rheumatoid arthritis subjects and healthy volunteers. One hundred twenty subjects were classified into different cohorts: healthy (H-C); periodontitis with good systemic health (H-P); rheumatoid arthritis (RA) and good periodontal health (RA-C); and periodontitis with RA (RA-P). The periodontal parameters were recorded, and SBS were collected to determine periodontal pathogens including Epstein-Barr Virus (EBV) and Candida albicans using reverse transcription-polymerase chain reaction (RT-PCR). Subjects that had greater disease course, determined by moderate or high disease activity scores 28 (DAS28), suffered from worse oral health conditions (higher plaque index, gingival index, bleeding on probing, probing depth, and excessive clinical attachment loss) than those with low DAS28 scores. A higher prevalence of Treponema denticola (T. denticola) was observed in the RA-P group. Cyclic citrullinated peptide was associated with the occurrence of T. denticola and Campylobacter rectus. DAS28 using C-reactive protein (DAS28-CRP) had a significant association with Capnocytophaga gingivalis and EBV. The duration of the RA disease was associated with the presence of T. denticola. Subgingival microbial difference could reliably discriminate RA from healthy individuals. Especially, T. denticola and EBV may play a key role in periodontitis associated with RA.

Effects of Nitrogen Application Rate and Plant Density on Severity of Tar Spot of Corn

Tar spot of corn, caused by the fungus Phyllachora maydis, is an economically important foliar disease recently reported in the United States and Canada. Due to the recent introduction of Phyllachora maydis, the impacts of cultural management practices on disease development are still unknown. Separate field studies were conducted to determine the effects of nitrogen (N) application rate and plant density on disease development. Field trials were conducted across six site years in Michigan with two corn hybrids of differing disease susceptibility. The relative area under the disease progress curve was used to compare disease development between N application rates and plant densities. Nitrogen application rate had no significant effect on disease at any location. Plant density and disease had a significant ( P &lt; 0.05) inverse relationship at five of six site years, with an average 41% decrease in the relative area under the disease progress curve for every 1,000 plants per hectare increase. The economically optimal planting density ranged from 73 to 77 thousand plants per hectare for US$150 to 300 per metric ton corn prices, demonstrating that relatively low planting densities were more profitable despite greater disease. Therefore, other disease management practices including hybrid selection may be more effective at protecting yield than increasing plant density.

CTNI-56. A MULTI-INSTITUTIONAL RETROSPECTIVE SERIES OF ADULT-ONSET MEDULLOBLASTOMA

Abstract Adult-onset medulloblastoma is a rare tumor for which limited data exists. Current treatment is based on data from childhood medulloblastoma. We present a retrospective cohort of 130 consecutive patients age ≥ 18 years and treated at the University of Washington (N = 61), University of Florida (N = 50), and Stanford University (N = 19), from 2000-2021. Median duration of follow-up was 57.3 months. Patients were 57.7% male (75/130), with median age at diagnosis of 29 years. 5 and 10-year overall survival were 78.9% and 67.6% and no recurrence was seen beyond 10 years. 31/130 (23.8%) patients had Chang M1 or greater disease and molecular typing was available for 41/130 patients. There was no improvement in progression-free survival (PFS) or overall survival (OS) either in patients who received proton therapy or those who received concurrent vincristine. There was a trend favoring longer OS in patients receiving radiotherapy within 6 weeks of surgery. A trend towards shorter OS in patients receiving a higher craniospinal radiation dose ( &amp;gt; 30Gy) likely reflected accurate clinical risk stratification. There was no improvement in OS or PFS for adjuvant chemotherapy overall, but patients receiving ≥ 5 cycles had improved PFS (HR 2.10, 95% CI = 1.19 - 3.90, p = 0.038) and a trend to improved OS (HR 2.07, 95%CI = 0.81-5.25, p = 0.125). After first progression, median OS was 20.7 months and both 5 and 10-year survival were 24.8%. We conclude that surveillance past 10 years may be unnecessary and that 1 in 4 patients achieve long-term survival after first relapse. Within the confines of a retrospective study, these data suggest equivalence between proton and photon radiotherapy, no benefit to concurrent vincristine, and that at least 5 cycles of adjuvant chemotherapy are required to delay progression.

Long-Term Results Following Use of Vaginal Electronic Brachytherapy in the Management of Endometrial Cancer

<h3>Purpose/Objective(s)</h3> We evaluated long-term vaginal toxicity and disease outcomes in women treated with vaginal electronic brachytherapy (EBT) following surgical management of endometrial cancer. <h3>Materials/Methods</h3> Women with endometrial cancer treated with adjuvant EBT were included in this study. Women diagnosed with uterine cancer of high-risk histology or advanced stage received EBT following completion of adjuvant chemotherapy. EBT was performed using a miniature low-energy (50-kV peak) X-ray source with a single-channel vaginal cylinder applicator to deliver radiation to the vagina along a specified length of the cylinder. EBT was delivered either as monotherapy or as a sequential boost following completion of pelvic external beam radiation (EBRT). EBT was delivered to 4 cm treatment length prescribed as 7 Gy to 5 mm depth x 3 fractions in the EBT alone group or 6 Gy to vaginal surface x 3 fractions in the EBT boost group. Following completion of EBT, patients were evaluated for all toxicities and recurrences. In this study, we evaluated for treatment related vaginal toxicity (stenosis) which was scored according to the Common Terminology Criteria for Adverse Events version 5.0. Multivariable analysis (MVA) of prognostic factors was performed using Cox Proportional-Hazards Model, and disease-free survival (DFS) and overall survival (OS) were estimated from date of surgery with Kaplan-Meier Method using data management and decision management software. <h3>Results</h3> 70 women were treated from 12/2017-6/2020 with EBT following hysterectomy. Median age of the cohort was 68 years (range, 51-85 years). 37 presented with endometrioid histologies. 32 received adjuvant chemotherapy prior to EBT. 21 presented with stage II or greater disease, and 20 received EBRT prior to EBT boost. EBT was delivered over a median interval of 1.3 weeks (range, 0.3-3.1 weeks). At a median follow-up of 25.0 months (range, 7.2-47.4 months), no patients were found to have ≥ grade 3 vaginal toxicity. The cumulative risk of developing gr 1 and 2 vaginal toxicity at 30 months was 25%. Prescription to 5 mm depth was the only factor associated with development of vaginal toxicity (p<0.05). One vaginal cuff recurrence, one locoregional recurrence, and ten distant recurrences were observed. Advanced tumor stage, high-risk histology, cervical stroma involvement, treatment with chemotherapy, and treatment with EBRT were significantly associated with inferior DFS/OS on MVA. DFS and OS in this group at 12 and 36 months were 94.2%/69.4% and 95.7%/88.3%, respectively. <h3>Conclusion</h3> EBT appears to be a safe, well-tolerated, and a promising alternative treatment option to traditional vaginal brachytherapy using a radioactive source. On MVA, prescription of EBT to 5 mm depth was associated with vaginal stenosis. One local recurrence was observed at 25 months follow-up. Risk of developing vaginal toxicity, DFS, and OS, following treatment with EBT in this heterogeneous population appear to be acceptable and comparable to historical controls (PORTEC 2 PMID 20206777).

Abstract 2355: Intratumoral translocation positive heterogeneity in pediatric alveolar rhabdomyosarcoma tumors correlates to changes in genes predicted to inhibit the immunological response

Abstract Alveolar rhabdomyosarcoma (ARMS) is characterized by one of three translocation states: t(2;13)(q35;q14) producing PAX3-FOXO1, t(1;13)(p36;q14) producing PAX7-FOXO1, or translocation-negative. Tumors with t(2;13) are associated with greater disease severity and mortality than t(1;13) positive or translocation negative patients. We demonstrated that ARMS tumor samples contain intratumoral genetic heterogeneity with respect to the presence of t(2;13). Further, we demonstrated that this heterogeneity had an inverse correlation with tumor aggressiveness, with tumors containing higher translocation positivity having lower failure-free survival of patients. However, it is not yet known whether a correlation exists between percent t(2;13) positivity and changes in gene expression, in particular genes whose function contributes to immune invasion in the tumor microenvironment. Of fifty-five rhabdomyosarcoma patient tumor samples received from Children’s Hospital in New Orleans, nine were confirmed to contain t(2;13) ranging from 16 - 98% cells positive for the translocation. We used aged-matched normal muscle tissue derived from autopsies as a control. RNA was isolated from whole tissue samples and analyzed using the Nanostring nCounter®️ PanCancer IO 360™ Panel. This panel contains 770 genes that specifically analyze tumor immunogenicity, tumor sensitivity to immune attack, inhibitory immune mechanisms, stromal factors, inhibitory metabolism, anti-tumor immune activity, inhibitory immune signaling, immune cell population and abundance, and tumor inflammation. We found 487 genes have an average change in expression ≥ 1.5-fold relative to the control. Of these genes 31 (6.4%) have a statistically significant positive correlation and nearly 25% (114 genes) had a statistically significant negative correlation to percent intratumoral translocation positivity. A closer examination indicated that genes with a negative correlation had biological functions that target a variety of different immunological processes. These include the recognition of antigen by T cells; the activation, maturation, and differentiation of lymphocytes and myeloid cells; adhesion of immune responsive cells; promotion of the inflammatory response; and activation of the innate immune response. These results suggest that increased intratumoral t(2;13) positivity negatively impacts the immunological response thereby increasing the ability for immune evasion of the tumors with higher levels of the translocation, a result consistent with our previously published work. Citation Format: Andrew D. Hollenbach, Matthew Stark, Jovanny Zabaleta, Fern Tsien. Intratumoral translocation positive heterogeneity in pediatric alveolar rhabdomyosarcoma tumors correlates to changes in genes predicted to inhibit the immunological response [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2355.

MP45-08 A COMPARISON OF BIOPSY GENOMIC TEST TO PREDICT ADVERSE DISEASE ON PROSTATECTOMY

You have accessJournal of UrologyCME1 May 2022MP45-08 A COMPARISON OF BIOPSY GENOMIC TEST TO PREDICT ADVERSE DISEASE ON PROSTATECTOMY Joon Yau Leong, Alex Uhr, Benjamin Rudnick, Andrea Quinn, Brian Calio, Edouard Trabulsi, Tingting Zhan, Leonard Gomella, Mark Mann, and Collaborators of PURC Joon Yau LeongJoon Yau Leong More articles by this author , Alex UhrAlex Uhr More articles by this author , Benjamin RudnickBenjamin Rudnick More articles by this author , Andrea QuinnAndrea Quinn More articles by this author , Brian CalioBrian Calio More articles by this author , Edouard TrabulsiEdouard Trabulsi More articles by this author , Tingting ZhanTingting Zhan More articles by this author , Leonard GomellaLeonard Gomella More articles by this author , Mark MannMark Mann More articles by this author , and Collaborators of PURC More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002611.08AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Despite progressively refined algorithms, it remains a challenge to accurately stratify patients with localized prostate cancer (PCa) into categories that correctly predict disease aggression and progression. Genomic analysis tests have attempted to remedy this with the addition of personalized cancer genomic risk categories which add proprietary genomic information into existing stratification algorithms. Currently, the three most commonly utilized tests on biopsy pathology are Oncotype DX, Decipher, and Prolaris. This study aimed to identify which genomic analysis test best predicts favorable or adverse pathology during radical prostatectomy. METHODS: Using data from the Pennsylvania Urologic Regional Collaborative (PURC), all patients who underwent genomic analysis on prostate biopsy with one of the three genomic tests, Oncotype DX, Decipher, or Prolaris were identified. Patients were divided into genomic risk categories and information on biopsy and prostatectomy pathology, treatment, and PSA was analyzed. RESULTS: No genomic analysis test was independently predictive of spread of disease outside the prostate. Patients with low genomic risk PCa as determined by Oncotype DX were statistically more likely to have a Grade Group (GG) upgrade compared to those in the intermediate risk group (p=0.045). When compared to patients with high Decipher genomic risk, patients with low risk on Decipher biopsy were statistically more likely to have a GG upgrade (p=0.027). For those who had Prolaris genomic analysis, patients with both low and intermediate genomic risk PCa were more likely to have a GG upgrade than patients with high genomic risk disease (p=0.001 and p<0.001 respectively). To examine GG upgrade risk, patients with either GG upgrade or pT3 or greater disease and PSA were compared across risk groups of each genomic analysis test in a multivariable logistic regression. There was no significant difference in upgrading risk between genomic risk levels for either Oncotype DX or Decipher. When compared to the high genomic risk patients, patients with low or intermediate genomic risk based on the Prolaris test were more likely to have a GG upgrade (p=0.001 and p=0.042 respectively). CONCLUSIONS: In our study, patients in the low-risk category for all three genetic test groups demonstrated significantly higher risk for GG upgrading than patients designated in each test group’s high-risk cohort. This gives providers heightened awareness of the persistent threat of more aggressive disease and possible progression despite a seemingly reassuring report from genomic testing. Source of Funding: None © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e765 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Joon Yau Leong More articles by this author Alex Uhr More articles by this author Benjamin Rudnick More articles by this author Andrea Quinn More articles by this author Brian Calio More articles by this author Edouard Trabulsi More articles by this author Tingting Zhan More articles by this author Leonard Gomella More articles by this author Mark Mann More articles by this author Collaborators of PURC More articles by this author Expand All Advertisement PDF DownloadLoading ...

MP51-12 THE ADDED VALUE OF MICROUS FOR THE PREOPERATIVE STAGING OF PROSTATE CANCER: AN UPDATE OF A SINGLE-INSTITUTIONAL PROSPECTIVE SERIES

You have accessJournal of UrologyCME1 May 2022MP51-12 THE ADDED VALUE OF MICROUS FOR THE PREOPERATIVE STAGING OF PROSTATE CANCER: AN UPDATE OF A SINGLE-INSTITUTIONAL PROSPECTIVE SERIES Vittorio Fasulo, Edoardo Beatrici, Luca Disconzi, Pier Paolo Avolio, Nicola Frego, Pietro Diana, Marco Paciotti, Davide Maffei, Alessandro Uleri, Cesare Saitta, Paola Arena, Giuseppe Chiarelli, Andrea Gobbo, Alberto Saita, Rodolfo Hurle, Massimo Lazzeri, Giorgio Guazzoni, Paolo Casale, Nicolò Maria Buffi, and Giovanni Lughezzani Vittorio FasuloVittorio Fasulo More articles by this author , Edoardo BeatriciEdoardo Beatrici More articles by this author , Luca DisconziLuca Disconzi More articles by this author , Pier Paolo AvolioPier Paolo Avolio More articles by this author , Nicola FregoNicola Frego More articles by this author , Pietro DianaPietro Diana More articles by this author , Marco PaciottiMarco Paciotti More articles by this author , Davide MaffeiDavide Maffei More articles by this author , Alessandro UleriAlessandro Uleri More articles by this author , Cesare SaittaCesare Saitta More articles by this author , Paola ArenaPaola Arena More articles by this author , Giuseppe ChiarelliGiuseppe Chiarelli More articles by this author , Andrea GobboAndrea Gobbo More articles by this author , Alberto SaitaAlberto Saita More articles by this author , Rodolfo HurleRodolfo Hurle More articles by this author , Massimo LazzeriMassimo Lazzeri More articles by this author , Giorgio GuazzoniGiorgio Guazzoni More articles by this author , Paolo CasalePaolo Casale More articles by this author , Nicolò Maria BuffiNicolò Maria Buffi More articles by this author , and Giovanni LughezzaniGiovanni Lughezzani More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002626.12AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: A stratification of patients with prostate cancer (PCa) before robotic-assisted radical prostatectomy (RARP) allows performing a tailor-made surgery, providing a nerve-sparing procedure even in those patients with high-risk PCa. Since the accuracy of clinical parameters to determine extraprostatic extension (EPE) is moderate, there is urgent need for imaging tools capable of providing a more accurate assessment. Our goal is to evaluate the added value of microUS in the preoperative prediction of EPE. METHODS: This is a prospective single-institutional cohort study enrolling patients with biopsy-proven PCa scheduled for RARP. Patients with PSA>20ng/mL and prostate volume>100 mL were excluded. All patients underwent microUS prior to RARP. MRI-derived features (curvilinear contact length (CCL), capsular bulging, visible extracapsular extension (ECE), as well as microUS features such as the presence of hypoechoic halo and obliteration of the vesicle-prostatic angle) were tested as predictors of EPE. Multivariable logistic regression models were fitted to test the accuracy of clinical parameters (total PSA, ISUP biopsy and digital rectal examination [DRE]) plus microUS parameters for the prediction of EPE. RESULTS: Overall, 184 patients were prospectively recruited. Besides CCL, all predictors were associated with non-organ- confined disease (p<0.001). Final pathology showed that 57.1% and 42.9% had respectively a pT2 and a pT3 or greater disease. The rate of non-organ-confined disease increased from 37.1%, in those individuals with only 1 predictor (OR 2.68), to 93.3% in those where 4 predictors were simultaneously observed (OR 63.5). At MLRM, the most significant risk factors for EPE were visible ECE (OR 5.21), positive DRE (OR 3.49), capsular bulge (OR 2.45), and PSA (OR 1.06). The clinical model alone showed an AUC of 0.804 as compared to 0.84 for the model including both clinical and microUS parameters (Figure1). The DeLong test for equality showed a difference between the two curves (p=0.0470). CONCLUSIONS: Our findings suggest that microUS may represent an accurate tool for the evaluation of non-organ confined PCa. Future studies should externally validate our findings and determine the impact of this tool in the surgical and oncological outcomes of RARP. Source of Funding: None © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e880 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Vittorio Fasulo More articles by this author Edoardo Beatrici More articles by this author Luca Disconzi More articles by this author Pier Paolo Avolio More articles by this author Nicola Frego More articles by this author Pietro Diana More articles by this author Marco Paciotti More articles by this author Davide Maffei More articles by this author Alessandro Uleri More articles by this author Cesare Saitta More articles by this author Paola Arena More articles by this author Giuseppe Chiarelli More articles by this author Andrea Gobbo More articles by this author Alberto Saita More articles by this author Rodolfo Hurle More articles by this author Massimo Lazzeri More articles by this author Giorgio Guazzoni More articles by this author Paolo Casale More articles by this author Nicolò Maria Buffi More articles by this author Giovanni Lughezzani More articles by this author Expand All Advertisement PDF DownloadLoading ...

Abstract 260: Provider Perspectives On Peripheral Artery Disease: Uncovering Practice Patterns That May Contribute To Health Disparities

Background: PAD is often undiagnosed and undertreated. Black American and Hispanic patients experience greater disease severity and worse outcomes compared to white patients. Applying the Kilbourne et al.’s comprehensive framework which identifies multilevel determinants of health disparities, we sought to understand why disparities exist by identifying provider factors that explain gaps in health and health care. Methods: Semi-structured in-depth interviews were conducted with 19 providers across diverse specialties from two clinical sites. Interviews occurred from November 2021 to February 2022. Domains of interest were provider factors that contribute to delays in diagnosis, treatment, and management of PAD, as well as how providers communicate with patients about PAD. Interviews were professionally transcribed and analyzed using a qualitative content analysis methodology. Findings: Specialists noted that the diagnosis of PAD may be delayed due to the lack of consistent early detection of risk factors and screening. PCPs felt that diagnosis of PAD is difficult due to patient under recognition of symptoms, symptoms mimicking other diseases, and asymptomatic patients. Both specialists and PCPs highlighted delayed PAD diagnosis due to a lack of clear guidelines for screening. Broader institutional constraints on screening for and diagnosing PAD related to time, resources, and logistics for both specialists and PCPs. There was general agreement that disease awareness and knowledge was lacking by both providers and patients, and may contribute to gaps in screening, treatment, and management of disease across the health care system. Some providers noted differences across populations in access to care and interventions, which may contribute to health disparities around PAD. Implications for Cardiovascular and Health Disparities Research: Overall, there is a clear sense among providers representing multiple disciplines that diagnosis of PAD is challenging. To address these challenges, more work needs to be to develop clinic team approaches to screen for PAD symptoms in at-risk patients. To close the gap in health disparities, patient perspectives should also be sought to better understand specific needs among different populations.

A Microbial Mutualist Within Host Individuals Increases Parasite Transmission Between Host Individuals: Evidence From a Field Mesocosm Experiment.

The interactions among host-associated microbes and parasites can have clear consequences for disease susceptibility and progression within host individuals. Yet, empirical evidence for how these interactions impact parasite transmission between host individuals remains scarce. We address this scarcity by using a field mesocosm experiment to investigate the interaction between a systemic fungal endophyte, Epichloë coenophiala, and a fungal parasite, Rhizoctonia solani, in leaves of a grass host, tall fescue (Lolium arundinaceum). Specifically, we investigated how this interaction impacted transmission of the parasite under field conditions in replicated experimental host populations. Epichloë-inoculated populations tended to have greater disease prevalence over time, though this difference had weak statistical support. More clearly, Epichloë-inoculated populations experienced higher peak parasite prevalences than Epichloë-free populations. Epichloë conferred a benefit in growth; Epichloë-inoculated populations had greater aboveground biomass than Epichloë-free populations. Using biomass as a proxy, host density was correlated with peak parasite prevalence, but Epichloë still increased peak parasite prevalence after controlling for the effect of biomass. Together, these results suggest that within-host microbial interactions can impact disease at the population level. Further, while Epichloë is clearly a mutualist of tall fescue, it may not be a defensive mutualist in relation to Rhizoctonia solani.

Effect of hypovitaminosis D on the characteristics of chronic tension-type headache in women

There is a growing body of evidence linking hypovitaminosis D with the prevalence and severity of various pain conditions. The effect of vitamin D levels on chronic tension type headache (CTTH) is almost unexplored.Objective: to investigate the effect of serum vitamin D levels on the clinical characteristics of CTTH.Patients and methods. The study enrolled women with CTTH (n=161). Headache frequency (HF), headache duration (HD), headache intensity (HI), presence of chronic widespread pain (WP) and the number of its zones, severity of anxiety and depression, and sleep quality index were evaluated. The vitamin D level was assessed by the concentration of 25-hydroxyvitamin D [25(OH)D].Results and discussion. Low 25(ОН)D-level was associated with an increase in HF, HD and the prevalence of WP. For each of the listed parameters, the values in vitamin D deficiency were higher than in its insufficiency or normal ranges (p&lt;0,001). 25(OH)D-level was inversely correlated with HF (rS=-0,49), HD (rS=-0,51; p&lt;0,05). Vitamin D-deficiency increased the risk of WP: compared to its insufficiency relative risk (RR) was 2.12 (95% CI 1.39–3.21), to the normal ranges – 3.67 (95% CI 1.71–7.88). In case of insufficiency and normal level of vitamin D, the values for the listed parameters did not differ. Other characteristics did not depend on 25(OH)D-level.Conclusion. In women with CTTH hypovitaminosis D contributes to the greater disease severity. Vitamin D deficiency, which is strongly associated with an increase in pain characteristics, has great clinical significance.

Loneliness, Lifestyles and Lockdowns: Effects on Health

Mother Teresa said: “the greatest disease in the West today is not TB or leprosy; it is being unwanted, unloved, and uncared for. We can cure physical diseases with medicine, but the only cure for loneliness, despair, and hopelessness is love...” Loneliness is a global phenomenon. Although more prevalent in the elderly, it is seen in all age groups. Contrary to logic, social media appears to have increased loneliness. Loneliness has several detrimental effects on human health. It is associated with a wide array of chronic diseases, contributing to their development, and often worsening their prognosis. Although there are several mechanisms involved in this harmful association, lower adherence to five healthy lifestyles is a major factor. These lifestyles include not smoking, not drinking alcohol in excess, maintaining adequate body weight, prudent diet, and regular physical activity. Unfortunately, unhealthy lifestyles have been aggravated by the recent COVID-19 pandemic. These relationships are reviewed in this manuscript.

Real-world clinical burden and economic assessment associated with hyperkalaemia in a large integrated healthcare system: a retrospective analysis

BackgroundHyperkalaemia (HK) is a serious and potentially life-threatening condition. Both acute and chronic conditions may alter potassium homeostasis. Our aim is to describe HK incidence, clinical outcomes, and associated resource use within a large, integrated healthcare system.MethodsAdult patients seen at Intermountain Healthcare facilities with a serum potassium (sK) result between January 1, 2003 and December 31, 2018 were retrospectively studied. Descriptive assessment of a population with detected HK, defined by any sK > 5.0 mmol/L and HK frequency and severity to associated resource use and characteristics of HK predictors were made. Multivariable Cox hazard regression was used to evaluate HK to outcomes.ResultsOf 1,208,815 patients included, 13% had HK. Compared to no-HK, HK patients were older (60 ± 18 vs 43 ± 18 years, P < 0.001), male (51% vs 41%, P < 0.001), and had greater disease burden (Charlson Comorbidity Index 3.5 ± 2.8 vs 1.7 ± 1.4, P < 0.001). At 3 years, more HK patients experienced major adverse cardiovascular events (MACEs) (19 vs 3%, P < 0.001), persisting post-adjustment (multivariable hazard ratio = 1.60, P < 0.001). They incurred higher costs for emergency department services ($552 ± 7,574 vs $207 ± 1,930, P < 0.001) and inpatient stays ($10,956 ± 93,026 vs $1,477 ± 21,423, P < 0.001). HyperK Risk Scores for the derivation and validation cohorts were: 44% low-risk, 45% moderate-risk, 11% high-risk. Strongest HK predictors were renal failure, dialysis, aldosterone blockers, diabetes, and smoking.ConclusionWithin this large system, HK was associated with a large clinical burden, affecting over 1 in 10 patients; HK was also associated with increased 3-year MACE risk and higher medical costs. Although risk worsened with more severe or persistently recurring HK, even mild or intermittent HK episodes were associated with significantly greater adverse clinical outcomes and medical costs. The HyperK Score predicted patients who may benefit from closer management to reduce HK risk and associated costs. It should be remembered that our assumptions are valid only for detected HK and not HK per se.

An exploration of wellbeing in men diagnosed with prostate cancer undergoing active surveillance: a qualitative study

PurposeThere is a growing emphasis on improving quality of life of people with prostate cancer. However, those undergoing active surveillance remain underrepresented in the literature with less known about their unique challenges. Therefore, we aimed to explore their lived experiences post diagnosis and its effect on their mental, social, and physical wellbeing.MethodsQualitative semi-structured interviews were conducted with 13 men undergoing active surveillance for low-risk disease. Thematic analysis was used to inductively co-construct themes through the lens of the biopsychosocial model.ResultsMental wellbeing was strongly affected in our participants due to the overwhelming emotional impact of their diagnosis resulting in an ‘Emotional Diagnostic Disequilibrium’. Informational awareness and education about prostate cancer helped patients with ‘Recognition of the Impact’. Patients experienced an ‘Unsettling Monitoring Cycle’ due to the increased fear and anxiety around PSA monitoring appointments, with some men ignoring their mental wellbeing needs as their disease is ‘A Future Problem’. ‘Concealment of Diagnosis’ left many feeling isolated and highlighted an important coping mechanisms in the ‘Importance of a Social Support Network’ theme. Finally, physical health mostly changed through alterations in health behaviour, leading to ‘A Healthier Lifestyle’ with increasing attribution of physical symptoms to age through ‘Symptomatic Overshadowing’.ConclusionThe greatest disease impact on men’s wellbeing was at the time of diagnosis, with a subsequent cyclical anxiety and fear of disease progression prominent around monitoring appointments. Future research should explore ways to better support patients with these issues and at these times, improving their quality of life.

Knowledge of Lassa fever, its prevention and control practices and their predictors among healthcare workers during an outbreak in Northern Nigeria: A multi-centre cross-sectional assessment

BackgroundThe year 2020 Lassa fever (LF) outbreak had the greatest disease burden and this can place an enormous strain on the already overstretched healthcare system and can potentially increase morbidity and mortality due to infectious diseases.Therefore, having a knowledgeable healthcare workforce with appropriate skills and competencies to prevent and manage outbreaks of a neglected infectious disease such as LF in Nigeria will potentially enhance public health. Thus, this survey assessed the level of knowledge of LF and its prevention and control (PC) measures amongst the healthcare workers (HCWs) during a LF outbreak in Katsina state, Nigeria.Methodology/Principal findingsDuring this cross-sectional survey, HCWs complete a validated 29-item questionnaire comprising 18 items on the knowledge of LF and its PC measures and an item on global self-evaluation of their LF knowledge. Psychometric properties of the questionnaire were evaluated. Chi-square and binary logistic regression analyses were conducted.Out of 435 HCWs invited, a total of 400 participated in the study (92% response rate). The majority of participants (51.8%) demonstrated inadequate LF knowledge, with 62.9% of those scoring low having a high self-perception of their LF knowledge with the global scale. This LF knowledge over-estimation was predicted by LF training status (odds ratio (OR) 2.53; 95% CI: 1.49–4.30; p = 0.001). The level of LF knowledge and its PC measures among the study participants was low (11.60±8.14, 64.4%) and predicted by participants’ LF training status (OR 2.06; 95% CI: 1.19–3.57; p = 0.009), place of work (OR 1.82; 95% CI: 1.07–3.08; p = 0.03) and their designations (OR 2.40; 95% CI: 1.10–5.22; p = 0.03).ConclusionThe level of knowledge of LF and its PC measures among the HCWs surveyed was suboptimal and participants’ LF training status, place of work and occupational category were the significant predictors. In addition, LF knowledge overestimation on a global scale was observed among a majority of HCWs and this was also predicted by LF training status. Therefore, there is a critical need for health authorities in Nigeria to prioritize continuous on-the-job training of HCWs on priority neglected tropical diseases such as Lassa fever.