Improving detection of carcinoma in situ in bladder cancer: urinary cytology vs the Xpert® BC Monitor.

OBJECTIVE: To investigate and compare the performance of urinary cytology and the Xpert BC Monitor test in the detection of bladder cancer in various clinically significant patient cohorts, including patients with carcinoma in situ (CIS), in a prospective multicentre setting, aiming to identify potential applications in clinical practice. PATIENTS AND METHODS: A total of 756 patients scheduled for transurethral resection of bladder tumour (TURBT) were prospectively screened between July 2018 and December 2020 at six German University Centres. Central urinary cytology and Xpert BC Monitor tests were performed prior to TURBT. The diagnostic performance of urinary cytology and the Xpert BC Monitor was evaluated according to sensitivity (SN), specificity (SC), negative predictive value (NPV) and positive predictive value (PPV). Statistical comparison of urinary cytology and the Xpert BC Monitor was conducted using the McNemar test. RESULTS: Of 756 screened patients, 733 (568 male [78%]; median [interquartile range] age 72 [62-79] years) were included. Bladder cancer was present in 482 patients (65.8%) with 258 (53.5%) high-grade tumours. Overall SN, SC, NPV and PPV were 39%, 93%, 44% and 92% for urinary cytology, and 75%, 69%, 59% and 82% for the Xpert BC Monitor. In patients with CIS (concomitant or solitary), SN, SC, NPV and PPV were 59%, 93%, 87% and 50% for urinary cytology, and 90%, 69%, 95% and 50% for the Xpert BC Monitor. The Xpert BC Monitor missed four tumours (NPV = 98%) in patients with solitary CIS, while potentially avoiding 63.3% of TURBTs in inconclusive or negative cystoscopy and a negative Xpert result. CONCLUSION: Positive urinary cytology may indicate bladder cancer and should be taken seriously. The Xpert BC Monitor may represent a useful diagnostic tool for correctly identifying patients with solitary CIS and unsuspicious or inconclusive cystoscopy.

Xpert bladder cancer monitor to predict the need for a second TURB (MoniTURB trial).

To determine whether Xpert bladder cancer monitor, a noninvasive PCR-based biomarker test, can predict the need for 2nd transurethral resection of the bladder (TURB) better than clinical assessment. Patients scheduled for TURB were prospectively screened. After initial TURB, patients were assigned to 2nd TURB or follow-up cystoscopy at 3 months (FU) by clinicians' discretion. Central urine cytology and Xpert monitor tests were performed prior to the 1st TURB and 2nd TURB or FU, respectively. Statistical analysis to compare clinical assessment and Xpert monitor comprised sensitivity (SENS), specificity (SPEC), NPV and PPV. Of 756 screened patients, 171 were included (114 with 2nd TURB, 57 with FU). Residual tumors were detected in 34 patients who underwent 2nd TURB, and recurrent tumors were detected in 2 patients with FU. SENS and SPEC of Xpert monitor were 83.3% and 53.0%, respectively, PPV was 32.6% and NPV was 92.1%. Clinical risk assessment outperformed Xpert monitor. In patients with pTa disease at initial TURB, Xpert monitor revealed a NPV of 96%. Xpert monitor was not superior than clinical assessment in predicting the need for 2nd TURB. It might be an option to omit 2nd TURB for selected patients with pTa disease.

Atrioventricular Coupling in Infants and Children Assessed by Three-Dimensional Echocardiography.

BACKGROUND: Parameters of the interaction of the left atrium and left ventricle, atrioventricular (AV) coupling, are used in the diagnosis and follow-up of diastolic dysfunction in adults. Pediatric parameters of AV coupling have not been evaluated so far. The aim of this multicenter study was to investigate parameters of AV coupling in a large cohort of healthy infants and children using noninvasive real-time three-dimensional echocardiography. The authors hypothesized that the contribution of the different left atrial (LA) volumes to left ventricular (LV) stroke volume differs over a range of different heart rates. METHODS: Three-dimensional echocardiographic data sets from 332 subjects (ages 0 days to 18.5 years) were analyzed prospectively. Volume-time curves of the left atrium and left ventricle were generated. Conduit volume was calculated and percentiles were established by the lambda-mu-sigma method of Cole and Green. Contributions of active, passive, and conduit volume to LV filling were measured and related to heart rate by linear regression. LV and LA peak filling rates (PFR) and peak emptying rates (PER) and time to PFR and PER normalized to the R-R interval (PFRt[%] and PERt[%]) were measured and correlated to each other. RESULTS: Conduit volume increased with body surface area. The contribution of LA active emptying to LV filling tended to increase with decreasing heart rate, while the contribution of passive emptying decreased. Conduit volume contributed most to LV filling (median, 57.58 %; interquartile range, 12.85%) with a tendency to increase with decreasing heart rate. Close diastolic AV coupling was demonstrated by virtually identical LV PFRt(%) and LA PERt(%) during diastole. LV PERt(%) occurred earlier than LA PFRt(%), showing less coupling during systole. LV PFRt(%) and LA PERt(%) were strongly correlated to heart rate (r = 0.76 and r = 0.73, respectively). Lower heart rate resulted in a prolongation of diastole after LV PFR. CONCLUSIONS: Assessment of conduit volume and AV coupling by three-dimensional echocardiography is feasible in infants and children. The references of this study can serve as a basis to further investigate the role of parameters of AV coupling in pediatric patients with heart diseases concerning diastolic and LA function.

C-reactive protein flare predicts response to anti-PD-(L)1 immune checkpoint blockade in metastatic urothelial carcinoma.

PURPOSE: Robust biomarkers to predict response to immune checkpoint blockade (ICB) in metastatic urothelial carcinoma (mUC) are still in demand. Recently, early C-reactive protein (CRP) kinetics and especially the novel CRP flare-response phenomenon has been associated with immunotherapy response. METHODS: We conducted a multicentre observational study comprising 154 patients with mUC treated with ICB to evaluate the predictive value of a previously described on-treatment CRP kinetics: CRP flare responders (at least doubling of baseline CRP within the first month after initiation of ICB followed by a decline below baseline within three months), CRP responders (decline in baseline CRP by ≥ 30% within three months without a prior flare) and the remaining patients as CRP non-responders. CRP kinetics groups were correlated with baseline parameters, PD-L1 status, progression-free survival (PFS) and overall survival (OS). RESULTS: Objective response was observed in 57.1% of CRP responders, 45.8% of CRP flare responders and 17.9% of CRP non-responders (P < 0.001). CRP flare response was associated with prolonged PFS and OS (P < 0.001). In multivariable Cox regression analysis, CRP flare responders showed a risk reduction of ∼70% for tumour progression and death compared to CRP non-responders. Subgroup analysis of CRP flare responders revealed that patients with a long-flare response (completed flare-response kinetics ≥6 weeks on-treatment) showed even more favourable outcomes following ICB (HR = 0.18, 95%-CI: 0.07-0.48, P < 0.001). CONCLUSION: CRP (flare)response robustly predicts immunotherapy response and outcomes in mUC independent of PD-L1 status. Thus, early on-treatment CRP kinetics is a promising low-cost and easy-to-implement biomarker to optimise therapy monitoring in patients with mUC treated with ICB.

Clinical Predictors of Neurogenic Lower Urinary Tract Dysfunction in Persons with Multiple Sclerosis.

BACKGROUND: Multiple sclerosis patients often develop neurogenic lower urinary tract dysfunction with a potential risk of upper urinary tract damage. Diagnostic tools are urodynamics, bladder diary, uroflowmetry, and post-void residual, but recommendations for their use are controversial. OBJECTIVE: We aimed to identify clinical parameters indicative of neurogenic lower urinary tract dysfunction in multiple sclerosis patients. METHODS: 207 patients were prospectively assessed independent of the presence of lower urinary tract symptoms. We analyzed Expanded Disability Status Scale scores, uroflowmetry, post-void residual, rate of urinary tract infections, standardized voiding frequency, and voided volume in correlation with urodynamic findings. RESULTS: We found a significant correlation between post-void residual (odds ratio (OR) 4.17, confidence interval (CI) 1.20-22.46), urinary tract infection rate (OR 3.91, CI 1.13-21.0), voided volume (OR 4.53, CI 1.85-11.99), increased standardized voiding frequency (OR 7.40, CI 2.15-39.66), and urodynamic findings indicative of neurogenic lower urinary tract dysfunction. Expanded Disability Status Scale shows no correlation. Those parameters (except post-void residual) are also associated with reduced bladder compliance, as potential risk for kidney damage. CONCLUSION: Therefore, bladder diary and urinary tract infection rate should be routinely assessed to identify patients who require urodynamics.

Left Atrial Volumes and Phasic Function in Healthy Children: Reference Values Using Real-Time Three-Dimensional Echocardiography.

BACKGROUND: Evaluation of left atrial (LA) size and function is important in congenital and acquired pediatric cardiac disease. Real-time three-dimensional echocardiography (3DE) offers noninvasive assessment of cardiac volumes and phasic function independent of geometric assumptions. The aim of this prospective multicenter study was to establish pediatric reference values for LA 3DE volumes and phasic function based on a large cohort of healthy children. METHODS: LA data sets of 432 subjects (0 days-222 months) were analyzed prospectively using a vendor-independent software. LA volumes (maximal [Vmax], minimal [Vmin], and before atrial contraction) as well as phasic function (active and passive emptying fraction [EF]) were assessed. For volumes, sex-specific reference values, percentiles, and z-scores were calculated by the LMS method of Cole and Green. RESULTS: Absolute volumes increased with age and body surface area. Active EF and relative duration of atrial emptying tended to increase with increasing R-R intervals, while passive EF decreased. Reproducibility of volumes was very good (intra- and interobserver variability for Vmax and Vmin (mean bias ± SD, 0.1 ± 0.9 mL and 0.7 ± 2.8 mL). Volumes were well correlated with cardiac magnetic resonance measurements showing known underestimation of volumes by 3DE (mean bias ± SD, Vmax -14.2 ± 14 mL; Vmin -11.5 ± 10 mL). CONCLUSIONS: Pediatric LA volumes and phasic function indices were reproducibly measured by 3DE. The provided pediatric reference values can be the basis for evaluation of the LA by 3DE and contribute to detection of LA dysfunction and follow-up of patients with congenital heart diseases.