Cumulative cancer locations on prostate biopsy and active surveillance outcomes in the MRI era.

BACKGROUND: To validate the use of a cumulative cancer locations (CCLO) score, a measurement of tumor volume on biopsy, and to develop a novel magnetic resonance imaging (MRI)-informed CCLO (mCCLO) score to predict clinical outcomes on active surveillance (AS). METHODS: The CCLO score is a sum of uniquely involved sextants with prostate cancer on diagnostic + confirmatory biopsy. The mCCLO score incorporates MRI findings into the CCLO score. Participants included 1284 individuals enrolled on AS between 1994 and 2022, 343 of whom underwent prostate MRI. The primary outcome was grade reclassification (GR) to grade group ≥2 disease; the secondary outcome was receipt of definitive treatment. RESULTS: Increasing CCLO and mCCLO risk groups were associated with higher risk of GR and undergoing definitive treatment (both p < 0.001). On multivariable analysis, increasing mCCLO score was associated with higher risk of GR and receipt of definitive treatment (hazard ratios [HRs] per 1-unit increase: 1.26 [95% confidence interval [CI]: 1.12-1.41] and 1.21 [95% CI: 1.07-1.36], respectively). The model using mCCLO score to predict GR (c-index: 0.671; 95% CI: 0.621-0.721) performed at least as well as models using the number of cores positive for cancer (0.664 [0.613-0.715]; p = 0.7) and the maximum percentage of cancer in a core (0.641 [0.585-0.696]; p = 0.14). CONCLUSIONS: The CCLO score is a valid, objective metric to predict GR and receipt of treatment in a large AS cohort. The ability of the MRI-informed mCCLO to predict GR is on par with traditional metrics of tumor volume but is more descriptive and may benefit from greater reproducibility. The mCCLO score can be implemented as a shorthand, informative tool for counseling patients about whether to remain on AS.

Retrospective Multicenter Observational Study of Immediate Voiding at End of Urinary Sphincter Surgery (REMOVE).

PURPOSE: Patients may remain catheterized after artificial urinary sphincter surgery to prevent urinary retention, despite a lack of evidence to support this practice. Our study aims to evaluate the feasibility of outpatient, catheter-free continence surgery using a multi-institutional database. We hypothesize that between catheterized controls and patients without a catheter, there would be no difference in the rate of urinary retention or postoperative complications. MATERIALS AND METHODS: We conducted a retrospective review of patients undergoing first-time artificial urinary sphincter placement from 2009-2021. Patients were stratified by postoperative catheter status into either no-catheter (leaving the procedure without a catheter) or catheter (postoperative indwelling catheter for ∼24 hours). The primary outcome, urinary retention, was defined as catheterization due to subjective voiding difficulty or documented postvoid residual over 250 mL. RESULTS: Our study identified 302 catheter and 123 no-catheter patients. Twenty (6.6%) catheter and 9 (7.3%) no-catheter patients developed urinary retention (P = .8). On multivariable analysis, controlling for age, cuff size, radiation history and surgeon, there was no statistically significant association between omitting a catheter and urinary retention (OR: 0.45, 95% CI: 0.13-1.58; P = .2). Furthermore, at 30 months follow-up, Kaplan-Meier survival analysis revealed that device survival was 70% (95% CI: 62%-76%) vs 69% (95% CI: 48%-82%) for the catheter and no-catheter group, respectively. CONCLUSIONS: In our multi-institutional cohort, overall retention rates were low (7%) in groups with a catheter and without. Obviating postoperative catheterization facilitates outpatient incontinence surgery without altering reoperation over medium-term follow-up.

Urology Consult: Association with Renal Trauma Imaging and Intervention.

OBJECTIVE: To describe rates of urology consultation following renal trauma and assess subsequent impact on imaging and intervention. Renal trauma may be initially managed by either trauma or urologic surgeons alone or collaboratively. Differences in management between the specialties are not well studied. METHODS: We conducted an IRB-approved retrospective review of patients at a Level I trauma center sustaining renal trauma between 2014 and 2021. Demographic, injury, radiologic, and intervention variables were extracted. Frequencies and medians were compared using chi-squared and Fischer's exact tests or Mann-Whitney U tests, respectively. Analyses were performed using STATA with P <.05 considered significant. RESULTS: From 2014 to 2021, 118 patients with median age 29 (IQR 22-41) sustained renal trauma. Urology was consulted in 18 (15.3%) cases. Demographic and injury characteristics were similar between the 2 groups. AAST renal injury grade was transcribed in the initial radiologic reports for 49 (41.5%) of patients. Those in the urology consult group were more likely to receive delayed contrast imaging during their admission (50.0% vs 17.0%, P <.01). Among those with high-grade injuries, those with urology consult were less likely to undergo nephrectomy (36.4% vs 78.8%, P = .02). CONCLUSION: We observed differences in imaging patterns between renal trauma patients who are managed primarily by trauma surgery versus urology. However, the impact of these differences in imaging remains to be elucidated. Among patients with high-grade renal trauma, urology consult was associated with decreased rate of nephrectomy, emphasizing the feasibility of renal salvage in a multidisciplinary trauma setting.

Opioid and Multimodal Analgesia Use Following Urological Trauma.

OBJECTIVE: To examine opioid use following Urological trauma. Increased opioid use is associated with inferior outcomes and risk of dependence, particularly in vulnerable populations. In contrast, multimodal analgesia following trauma allows decreased pain and readmission. Currently there is a paucity of data describing opioid usage following urological trauma. The purpose of this study was to assess utilization of opioids and multimodal pain regimens following urologic trauma. METHODS: We retrospectively examined 116 patients hospitalized following urologic trauma from 2016-2021. Inpatient and discharge utilization of opioids, multimodal analgesia and length of stay were stratified by affected organ. Analyses were performed in STATA with p<0.05 reaching significance. RESULTS: 116 patients were assessed; 84 (72.4%) required surgery. In the first 10 days, bladder injuries incurred higher mean and median OMEQ than other urological injuries. In nearly all groups, OMEQ prescribed at discharge is less than average inpatient OMEQ. Eighty-six (74.1%) patients received at least 2 different opioid medications while inpatient. Those with a history of opioid use received a significantly higher OMEQ dose per day (p<0.001). There were no significant differences between opioid prescribing patterns or average OMEQ dosages prescribed at discharge between those patients managed either surgically or non-operatively. Only 24 (20.7%) patients met the criteria for utilization of multimodal analgesia. CONCLUSION: Multimodal analgesia is severely underutilized following urological trauma. Combined with the development of opioid tolerance over long hospital stays, this creates an avenue for opioid misuse following discharge and provides an opportunity for improvement.

Assessing COVID-19 Health Information on Google Using the Quality Evaluation Scoring Tool (QUEST): Cross-sectional and Readability Analysis.

BACKGROUND: The COVID-19 pandemic spurred an increase in online information regarding disease spread and symptomatology. OBJECTIVE: Our purpose is to systematically assess the quality and readability of articles resulting from frequently Google-searched COVID-19 terms in the United States. METHODS: We used Google Trends to determine the 25 most commonly searched health-related phrases between February 29 and April 30, 2020. The first 30 search results for each term were collected, and articles were analyzed using the Quality Evaluation Scoring Tool (QUEST). Three raters scored each article in authorship, attribution, conflict of interest, currency, complementarity, and tone. A readability analysis was conducted. RESULTS: Exactly 709 articles were screened, and 195 fulfilled inclusion criteria. The mean article score was 18.4 (SD 2.6) of 28, with 7% (14/189) scoring in the top quartile. National news outlets published the largest share (70/189, 36%) of articles. Peer-reviewed journals attained the highest average QUEST score compared to national/regional news outlets, national/state government sites, and global health organizations (all P<.05). The average reading level was 11.7 (SD 1.9, range 5.4-16.9). Only 3 (1.6%) articles were written at the recommended sixth grade level. CONCLUSIONS: COVID-19-related articles are vastly varied in their attributes and levels of bias, and would benefit from revisions for increased readability.

Differential Activity of PARP Inhibitors in BRCA1- Versus BRCA2-Altered Metastatic Castration-Resistant Prostate Cancer.

Two poly (ADP-ribose) polymerase (PARP) inhibitors (olaparib and rucaparib) are US Food and Drug Administration-approved for patients with metastatic castration-resistant prostate cancer (mCRPC) harboring BRCA1/2 mutations, but the relative efficacy of PARP inhibition in BRCA1- versus BRCA2-altered mCRPC is understudied. METHODS: We conducted a multicenter retrospective analysis involving 12 sites. We collected genomic and clinical data from 123 patients with BRCA1/2-altered mCRPC who were treated with PARP inhibitors. The primary efficacy end point was the prostate-specific antigen (PSA) response (≥ 50% PSA decline) rate. Secondary end points were PSA progression-free survival (PSA-PFS), clinical or radiographic PFS, and overall survival. We compared clinical outcomes, and other genomic characteristics, among BRCA1- versus BRCA2-altered mCRPC. RESULTS: A total of 123 patients (13 BRCA1 and 110 BRCA2) were included. PARP inhibitors used were olaparib (n = 116), rucaparib (n = 3), talazoparib (n = 2), and veliparib (n = 2). At diagnosis, 72% of patients had Gleason 8-10 disease. BRCA1 patients were more likely to have metastatic disease at presentation (69% v 37%; P = .04). Age, baseline PSA, metastatic distribution, and types of previous systemic therapies were similar between groups. There were equal proportions of germline mutations (51% v 46%; P = .78) in both groups. BRCA1 patients had more monoallelic (56% v 41%; P = .49) and concurrent TP53 (55% v 36%; P = .32) mutations. PSA50 responses in BRCA1- versus BRCA2-altered patients were 23% versus 63%, respectively (P = .01). BRCA2 patients achieved longer PSA-PFS (HR, 1.94; 95% CI, 0.92 to 4.09; P = .08), PFS (HR, 2.08; 95% CI, 0.99 to 4.40; P = .05), and overall survival (HR, 3.01; 95% CI, 1.32 to 6.83; P = .008). Biallelic (compared with monoallelic) mutations, truncating (compared with missense) mutations, and absence of a concurrent TP53 mutation were associated with PARP inhibitor sensitivity. CONCLUSION: PARP inhibitor efficacy is diminished in BRCA1- versus BRCA2-altered mCRPC. This is not due to an imbalance in germline mutations but might be related to more monoallelic mutations and/or concurrent TP53 alterations in the BRCA1 group.

Targeting the IGF1R/PI3K/AKT Pathway Sensitizes Ewing Sarcoma to BET Bromodomain Inhibitors.

Inhibitors of the bromodomain and extra-terminal domain (BET) family proteins modulate EWS-FLI1 activities in Ewing sarcoma. However, the efficacy of BET inhibitors as a monotherapy was moderate and transient in preclinical models. The objective of this study was to identify the mechanisms mediating intrinsic resistance to BET inhibitors and develop more effective combination treatments for Ewing sarcoma. Using a panel of Ewing sarcoma cell lines and patient-derived xenograft lines (PDX), we demonstrated that IGF1R inhibitors synergistically increased sensitivities to BET inhibitors and induced potent apoptosis when combined with BET inhibitors. Constitutively activated AKT significantly protected Ewing sarcoma cells against BET inhibitors, suggesting that IGF1R regulates responsiveness to BET inhibitors mainly through the PI3K/AKT pathway. Although two Ewing sarcoma cell lines were resistant to IGF1R inhibitors, they retained synergistic response to a combination of BET inhibitors and mTOR inhibitors, suggesting that BET proteins, when IGF1R is not functional, cross-talk with its downstream molecules. Furthermore, the combination of a BET inhibitor and an IGF1R inhibitor induced potent and durable response in xenograft tumors, whereas either agent alone was less effective. Taken together, our results suggest that IGF1R and the downstream PI3K/AKT/mTOR kinase cascade mediate intrinsic resistance to BET inhibitors in Ewing sarcoma. These results provide the proof-of-concept for combining BET inhibitors with agents targeting the IGF1R pathway for treating advanced Ewing sarcoma.

Adding "hemodynamic and fluid leads" to the ECG. Part I: the electrical estimation of BNP, chronic heart failure (CHF) and extracellular fluid (ECF) accumulation.

OBJECTIVES: In primary care the diagnosis of CHF and ECF accumulation is no triviality. We aimed to predict plasma BNP, CHF and ECF accumulation with segmental impedance spectroscopy while using and extending the electrodes of the conventional electrocardiography. METHODS: Three combined multiple electrodes were added to the 15 lead ECG for segmental impedance spectroscopy and for measuring the maximal rate of segmental fluid volume change with heart action at the thorax and the legs. The obtained signals were analyzed by partial correlation analyses in comparison with plasma BNP, CHF classes, ejection fraction by echocardiography and cardiac index by double gas re-breathing. 119 subjects (34 healthy volunteers, 50 patients with CHF, NYHA classes II to IV and 35 patients without CHF) were investigated. RESULTS: The maximal rate of volume change with heart action at the thorax and at the legs, as well as the ECF/ICF ratio at the legs contribute equally and independently to the prediction of BNP and heart failure in an unknown test sample of 49 patients (multiple r=0.88, p<0.001). The ROC-curve for the predicted plasma BNP>400 pg/ml gave an AUC=0.93. The absence or the presence of heart failure could be predicted correctly by a binomial logistic regression in 92.9 and 87.5% of cases, respectively. CONCLUSION: The methodology, which is based on inverse coupling of BNP release and of maximal blood acceleration and on sensitive detection of ECF overload, could enable the diagnosis of CHF with useful sensitivity and specificity while writing a routine-ECG.

Multi-site-frequency electromechanocardiography for the prediction of ejection fraction and stroke volume in heart failure.

BACKGROUND: Methods for stroke volume (SV) and ejection fraction (EF) measurements require the presence of qualified physicians and are not suited for continuous monitoring. AIM: To develop an automated non-invasive method for the measurement and continuous monitoring of SV and EF. METHODS: We have designed a method for the measurement of EF and SV using multiple-site-impedance (z0) measurements, applying multiple frequencies of 5, 40 and 200 kHz whereby various segments of the human body, including volume changes within these segments, could be defined electrically. The obtained variables were used to train neuronal nets and related by multiple regression analyses to cardiac output (CO) as measured by a partial rebreathing Fick method (CO(r-fick)) or EF as measured by echocardiography (EF(echo)), respectively. A total of 129 subjects (48 with normal heart function and 81 with CHF, NYHA I-IV) were investigated. RESULTS: The multiply derived values of z0 and of change of impedance (dz/dt) were shown, by multiple regression analysis, to be significantly related to CO(r-fick) and to EF(echo), (total r=0.77, n=35, p<0.001, and r=0.81, n=47, p<0.001, respectively.). By training a neuronal net with the electrical data of 67 (out of 94) subjects, EF(echo) could be predicted in the remaining 27 subjects which were unknown to the neuronal net with a combined r=0.71 (p<0.001,n=27). In contrast, conventional impedance cardiography (ICG) was unable to predict either CO(r-fick) or EF(echo). CONCLUSION: The new method, which we call multi-site-frequency electromechanocardiography (msf-ELMC) appears promising for the automated electrical measurement of the mechanical heart action in patients with normal and reduced cardiac function.