Intravesical Resiniferatoxin for the Treatment of Storage Lower Urinary Tract Symptoms in Patients with Either Interstitial Cystitis or Detrusor Overactivity: A Meta-Analysis

<div><p>Background</p><p>While Resin­iferatoxin (RTX) has been widely used for patients with storage lower urinary tract symptoms (LUTS), its clinical efficiency hasn't yet been well evaluated. A meta-analysis was performed to evaluate the exact roles of intravesical RTX for the treatment of storage LUTS in patients with either interstitial cystitis (IC) or detrusor overactivity (DO).</p><p>Methods</p><p>A meta-analysis of RTX treatment was performed through a comprehensive search of the literature. In total, 2,332 records were initially recruited, 1,907 from Elsevier, 207 from Medline and 218 from the Web of Science. No records were retrieved from the Embase or Cochrane Library. Seven trials with 355 patients were included and one trial was excluded because of the lack of extractable data. The analyses were all performed using RevMan 5.1 and MIX 2.0.</p><p>Results</p><p>Bladder pain was significantly reduced after RTX therapy in patients with either IC or DO. The average decrease of the visual an alogue pain scale was 0.42 after RTX treatment (p = 0.02). The maximum cystometric capacity (MCC) was significantly increased in patients with DO (MCC increase, 53.36 ml, p = 0.006) but not in those with IC (MCC increase, −19.1 ml, p = 0.35). No significant improvement in urinary frequency, nocturia, incontinence or the first involuntary detrusor contraction (FDC) was noted after RTX therapy (p = 0.06, p = 0.52, p = 0.19 and p = 0.41, respectively).</p><p>Conclusions</p><p>RTX could significantly reduce bladder pain in patients with either IC or DO, and increase MCC in patients with DO; however, no significant improvement was observed in frequency, nocturia, incontinence or FDC. Given the limitations in the small patient size and risk of bias in the included trials, great caution should be taken when intravesical RTX is used before a large, multicenter, well-designed random control trial with a long-term follow-up is carried out to further assess the clinical efficacy of RTX in in patients with storage LUTS.</p></div

Visual an­alogue scale (VAS) score changes for bladder pain in all the patients (A; average decrease of VAS score 0.42, 95% CI 0.07 to 0.76, p = 0.02) and subgroup analyses in patients with either interstitial cystitis (IC) or detrusor overactivity (DO) (B; average decrease of VAS score for IC 0.35, 95% CI 0 to 0.7, p = 0.05; average decrease of VAS score for DO 1.4, 95% CI 0.03 to 2.77, p = 0.05).

<p>Visual an­alogue scale (VAS) score changes for bladder pain in all the patients (A; average decrease of VAS score 0.42, 95% CI 0.07 to 0.76, p = 0.02) and subgroup analyses in patients with either interstitial cystitis (IC) or detrusor overactivity (DO) (B; average decrease of VAS score for IC 0.35, 95% CI 0 to 0.7, p = 0.05; average decrease of VAS score for DO 1.4, 95% CI 0.03 to 2.77, p = 0.05).</p

Flowchart of literature searches and results.

<p>In this meta-analysis, eight studies were selected for qualitative analysis. Of these eight studies, seven eligible controlled trials with 355 patients were included in our meta-analysis while the remaining one trial was excluded because of the lack of extractable data.</p

FDC (A; mean difference −16.56 ml, 95% CI −55.79 to 22.67 ml, p = 0.41) and MCC (B; mean difference 34ml, 95% CI -16.54 to 84.53ml, p = 0.19) changes in all the patients and subgroup analyses of MCC in patients with either interstitial cystitis (IC) or detrusor overactivity (DO) (C; MCC mean difference for IC −19.10 ml, 95% CI −59.37 to 21.17 ml, p = 0.35; MCC mean difference for DO 53.36 ml, 95%CI 15.42 to 91.29 ml, p = 0.006).

<p>FDC (A; mean difference −16.56 ml, 95% CI −55.79 to 22.67 ml, p = 0.41) and MCC (B; mean difference 34ml, 95% CI -16.54 to 84.53ml, p = 0.19) changes in all the patients and subgroup analyses of MCC in patients with either interstitial cystitis (IC) or detrusor overactivity (DO) (C; MCC mean difference for IC −19.10 ml, 95% CI −59.37 to 21.17 ml, p = 0.35; MCC mean difference for DO 53.36 ml, 95%CI 15.42 to 91.29 ml, p = 0.006).</p

Nocturia changes in all the patients (A; mean difference −0.16, 95% CI −0.64 to 0.33, p = 0.52) and subgroup analyses of nocturia in patients with either interstitial cystitis (IC) or detrusor overactivity (DO) (B; mean difference for IC −0.25, 95% CI −1.00 to 0.49, p = 0.51; mean difference for DO −0.09, 95% CI −0.73 to 0.55, p = 0.78). Incontinence changes in all the patients (C; mean difference −2.26, 95% CI −5.68 to 1.15, p = 0.19).

<p>Nocturia changes in all the patients (A; mean difference −0.16, 95% CI −0.64 to 0.33, p = 0.52) and subgroup analyses of nocturia in patients with either interstitial cystitis (IC) or detrusor overactivity (DO) (B; mean difference for IC −0.25, 95% CI −1.00 to 0.49, p = 0.51; mean difference for DO −0.09, 95% CI −0.73 to 0.55, p = 0.78). Incontinence changes in all the patients (C; mean difference −2.26, 95% CI −5.68 to 1.15, p = 0.19).</p

Characteristics of included trials.

<p>R = patients treated with RTX, N =  controls, B =  the baseline symptom, P =  the post-treatment symptom.</p><p>“*” =  No. of incontinence episodes/3-day voiding diary, “−” =  data unavailable.</p><p>Data are expressed by mean ± standard deviation.</p

Quality assessment in this meta-analysis demonstrated a low risk of bias in five studies (Rios 2007, Kuo 2006, Payne 2005, Silva 2005 and Chen 2005) and a relatively high risk of bias in the remaining two studies (Ham 2012 and Lazzeri 2000).

<p>Quality assessment in this meta-analysis demonstrated a low risk of bias in five studies (Rios 2007, Kuo 2006, Payne 2005, Silva 2005 and Chen 2005) and a relatively high risk of bias in the remaining two studies (Ham 2012 and Lazzeri 2000).</p

Well-Paired-Seq2: High-Throughput and High-Sensitivity Strategy for Characterizing Low RNA-Content Cell/Nucleus Transcriptomes

Single-cell RNA sequencing (scRNA-seq) is a transformative technology that unravels the intricate cellular state heterogeneity. However, the Poisson-dependent cell capture and low sensitivity in scRNA-seq methods pose challenges for throughput and samples with a low RNA-content. Herein, to address these challenges, we present Well-Paired-Seq2 (WPS2), harnessing size-exclusion and quasi-static hydrodynamics for efficient cell capture. WPS2 exploits molecular crowding effect, tailing activity enhancement in reverse transcription, and homogeneous enzymatic reaction in the initial bead-based amplification to achieve 3116 genes and 8447 transcripts with an average of ∼20000 reads per cell. WPS2 detected 1420 more genes and 4864 more transcripts than our previous Well-Paired-Seq. It sensitively characterizes transcriptomes of low RNA-content single cells and nuclei, overcoming the Poisson limit for cell and barcoded bead capture. WPS2 also profiles transcriptomes from frozen clinical samples, revealing heterogeneous tumor copy number variations and intercellular crosstalk in clear cell renal cell carcinomas. Additionally, we provide the first single-cell-level characterization of rare metanephric adenoma (MA) and uncover potential specific markers. With the advantages of high sensitivity and high throughput, WPS2 holds promise for diverse basic and clinical research

Age-Specific Cutoff Value for the Application of Percent Free Prostate-Specific Antigen (PSA) in Chinese Men with Serum PSA Levels of 4.0–10.0 ng/ml

<div><p>Objective</p><p>The influence of age on the performance of percent free prostate-specific antigen (%fPSA) in diagnosing prostate cancer (PCa) in East Asians is controversial. We tested the diagnostic performance of %fPSA in a multi-center biopsy cohort in China and identified the proper age-specific cutoff values to avoid unnecessary biopsies.</p><p>Methods</p><p>Consecutive patients with a prostate-specific antigen (PSA) level of 4.0–10.0 ng/ml or 10.1–20.0 ng/ml who underwent transrectal ultrasound-guided or transperineal prostate biopsy were enrolled from 22 Chinese medical centers from Jan 1, 2010 to Dec 31, 2013. The diagnostic accuracy of PSA and %fPSA was determined using the area under the receiver operating characteristic (ROC) curve (AUC). Age-specific cutoff values were calculated using ROC curve analysis.</p><p>Results</p><p>The median %fPSA was much lower in younger patients compared with older patients with a PSA level of 4.0–10.0 ng/ml or 10.1–20.0 ng/ml. The AUC of %fPSA was higher than PSA only in older patients. In patients aged 50 to 59 years, %fPSA failed to improve the diagnosis compared with PSA in these two PSA ranges. Age-specific cutoff values were 24%, 27% and 32% for patients aged 60–69, 70–79 and ≥80 years, respectively, to reduce unnecessary biopsies in men with PSA levels of 4.0–10.0 ng/ml to detect 90% of all PCa.</p><p>Conclusions</p><p>The effectiveness of %fPSA is correlated with age in the Chinese population. Age-specific cutoff values would help avoid unnecessary biopsies in the Chinese population.</p></div

ROC curves of %fPSA and PSA for any PCa.

<p>ROC curves of %fPSA and PSA in predicting any prostate cancer for patients aged (A) 50–59 years; (B) 60–69 years; (C) 70–79 years; and (D) 80–89 years with a PSA level of 4.0–10.0 ng/ml.</p