In vivo assessment of bladder cancer with diffuse reflectance and fluorescence spectroscopy: A comparative study.

OBJECTIVES: The aim of this work is to assess the performance of multimodal spectroscopic approach combined with single core optical fiber for detection of bladder cancer during surgery in vivo. METHODS: Multimodal approach combines diffuse reflectance spectroscopy (DRS), fluorescence spectroscopy in the visible (405 nm excitation) and near-infrared (NIR) (690 nm excitation) ranges, and high-wavenumber Raman spectroscopy. All four spectroscopic methods were combined in a single setup. For 21 patients with suspected bladder cancer or during control cystoscopy optical spectra of bladder cancer, healthy bladder wall tissue and/or scars were measured. Classification of cancerous and healthy bladder tissue was performed using machine learning methods. RESULTS: Statistically significant differences in relative total haemoglobin content, oxygenation, scattering, and visible fluorescence intensity were found between tumor and normal tissues. The combination of DRS and visible fluorescence spectroscopy allowed detecting cancerous tissue with sensitivity and specificity of 78% and 91%, respectively. The addition of features extracted from NIR fluorescence and Raman spectra did not improve the quality of classification. CONCLUSIONS: This study demonstrates that multimodal spectroscopic approach allows increasing sensitivity and specificity of bladder cancer detection in vivo. The developed approach does not require special probes and can be used with single-core optical fibers applied for laser surgery.

Predictive potential of ACE phenotyping in extrapulmonary sarcoidosis.

Elevated ACE expression in tissues (reflected by blood ACE levels) is associated with increased risk of cardiovascular diseases and is also a marker for granulomatous diseases. We developed a new approach for characterization of ACE status in the blood-ACE phenotyping and established normal values of ACE levels 50-150% of control pooled plasma. ACE phenotyping was performed in citrated plasma of 120 patients with known interstitial lung diseases. In the 1st set of 100 patients we found 22 patients with ACE levels > 150%; ACE phenotyping also objectively identified the presence of ACE inhibitors in the plasma of 15 patients. After excluding these patients and patient with ACE mutation that increases ACE shedding, 17 patients were identified as a suspicious for systemic sarcoidosis based on elevation of blood ACE (> 150% of mean). A new parameter that we have established-ACE immunoreactivity (with mAb 9B9)-allowed us to detect 22 patients with decreased values (< 80%) of this parameter, which may indicate the presence of ACE in the blood that originates from macrophages/dendritic cells of granulomas. In the remaining 20 patients, this new parameter (mAbs binding/activity ratio) was calculated using 3 mAbs (9B9, 3A5 and i1A8-having overlapping epitopes), and 8 patients were identified as having decreases in this parameter, thus increasing dramatically the sensitivity for detection of patients with systemic sarcoidosis. Whole body PET scan confirmed extrapulmonary granulomas in some patients with lower immunoreactivity towards anti-ACE mAbs. ACE phenotyping has novel potential to noninvasively detect patients with systemic sarcoidosis.

The Association of PLAUR Genotype and Soluble suPAR Serum Level with COVID-19-Related Lung Damage Severity.

Uncovering the risk factors for acute respiratory disease coronavirus 2019 (COVID-19) severity may help to provide a valuable tool for early patient stratification and proper treatment implementation, improving the patient outcome and lowering the burden on the healthcare system. Here we report the results of a single-center retrospective cohort study on 151 severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2)-infected symptomatic hospitalized adult patients. We assessed the association of several blood test measurements, soluble urokinase receptor (uPAR) serum level and specific single nucleotide polymorphisms of ACE (I/D), NOS3 (rs2070744, rs1799983), SERPINE1 (rs1799768), PLAU (rs2227564) and PLAUR (rs344781, rs2302524) genes, with the disease severity classified by the percentage of lung involvement on computerized tomography scans. Our findings reveal that the T/C genotype of PLAUR rs2302524 was independently associated with a less severe lung damage (odds ratio 0.258 [0.071-0.811]). Along with high C-reactive protein, fibrinogen and soluble uPAR serum levels turned out to be independently associated with more severe lung damage in COVID-19 patients. The identified factors may be further employed as predictors of a possibly severe COVID-19 clinical course.

Prediction of reproductive function recovery after microsurgical varicocelectomy in men from infertile couples: Clinical and laboratory predictors.

The objective was to reveal predictors for fertility recovery after varicocelectomy in subfertile men. This retrospective study recruited 93 men with clinical varicocele and pathozoospermia who underwent microsurgical varicocelectomy. Stepwise discriminant analysis was performed to identify predictors of spontaneous pregnancy (SP) after surgery. 'Clinically significant improvement' (CSI) following varicocelectomy was defined as an increase in total progressively motile sperm count (TPMSC) by at least 12.5 million (calculated from WHO-2010 reference values). 52% of patients showed CSI, and 28% reported SP after surgery. Patients who reported SP (group II), compared to that remained infertile (group I), were younger (27.3 ± 2.9 versus 30.2 ± 4.2 years; p < .01), had less infertility period (24.1 ± 14.0 versus 44.4 ± 32.9 months; p < .05) and had initially higher TPMSC (median (25% -75%) = 34 (11-67) versus 9.5 (0-33) mln; p < .05). The stepwise discriminant analysis showed that male age (coefficient value = -0.157), total sperm motility (0.024) and postoperative increase in TPMSC (0.010) were the significant predictors of SP. The predictive ability, sensitivity and specificity of the discriminant function were 84%, 87%, 76% respectively. This algorithm can be recommended after varicocelectomy in decision-making on natural conception or the ART protocols usage.

Activating Telomerase TERT Promoter Mutations and Their Application for the Detection of Bladder Cancer.

This review summarizes state-of-the-art knowledge in early-generation and novel urine biomarkers targeting the telomerase pathway for the detection and follow-up of bladder cancer (BC). The limitations of the assays detecting telomerase reactivation are discussed and the potential of transcription-activating mutations in the promoter of the TERT gene detected in the urine as promising simple non-invasive BC biomarkers is highlighted. Studies have shown good sensitivity and specificity of the urinary TERT promoter mutations in case-control studies and, more recently, in a pilot prospective cohort study, where the marker was detected up to 10 years prior to clinical diagnosis. However, large prospective cohort studies and intervention studies are required to fully validate their robustness and assess their clinical utility. Furthermore, it may be interesting to evaluate whether the clinical performance of urinary TERT promoter mutations could increase when combined with other simple urinary biomarkers. Finally, different approaches for assessment of TERT promoter mutations in urine samples are presented together with technical challenges, thus highlighting the need of careful technological validation and standardization of laboratory methods prior to translation into clinical practice.

Incidence and predictors of urinary incontinence rates after thulium fiber laser enucleation of prostate performed by single surgeon.

Purpose: We aimed to evaluate the predictive clinical and operative risk factors for urinary incontinence (UI) rates following thulium fiber enucleation of benign prostate hyperplasia (ThuFLEP). Materials and methods: We conducted a retrospective cohort review of a prospectively maintained database for patients who underwent ThuFLEP between 2021 and 2023 in our university clinic performed by a single surgeon with high experience (more than 3000 endoscopic enucleation). To perform the operation, we used a thulium fiber laser Fiberlase U3 (IRE Polus ltd, Fryazino, Russia) with operating modes of 1.5 J and 40 Hz 60 W. Postoperative UI rates and risk factors following ThuFLEP were assessed for three follow-up intervals (up to 1 months, from 1 to 3 months and after 3 months post-ThuFLEP). Statistical analysis was conducted using univariate and multivariate logistic regression. Results: Out of total 578 patients who underwent ThuFLEP, the study included 381 patients with full information about continence status. Long-term UI (more than 3 months) were found only in 1.6% cases with 0.8% for stress UI, 0.3% for urge UI and 0.5% for mixed UI. Univariate logistic regression analysis has shown that higher total laser energy (OR = 1.009; 95% CI = 1.001-1.018; p = 0.036) and enucleation technique (OR = 0.272; 95% CI = 0.113-0.656; p = 0.004 in favor of En-bloc ThuFLEP) were associated with UI overall, while at multivariable analysis only En-bloc ThuFLEP was protective factor for UI (OR = 0.302; 95%CI = 0.123-0.739; p = 0.009). For short-term UI (less than 1 months) early sphincter release was found as protective factor at both uni- and multivariate analysis compare to longer UI. Conclusion: Short-term UI up to 3 months following ThuFLEP is associated with early sphincter release, while overall UI rates are related with enucleation technique (preferable En-bloc) and total laser energy (preferable lower energy). The surgeon should take all these risk factors into account before choosing the technique of BPH surgical treatment.

Propensity score-matched analysis comparing perioperative, functional, and safety outcomes between thulium fiber laser and bipolar enucleation of the prostate performed by a single surgeon with two years of follow-up.

PURPOSE: To compare perioperative, functional, and safety outcomes between thulium fiber laser enucleation of the prostate (ThuFLEP) and bipolar enucleation of the prostate performed by a single surgeon with use of propensity score (PS)-matched analysis. MATERIALS AND METHODS: Data were from 675 patients, 422 of whom underwent ThuFLEP and bipolar enucleation by a single highly experienced surgeon. ThuFLEP was performed with Fiberlase U1 (IRE Polus Ltd.). Perioperative parameters, safety, and functional outcomes, such as International Prostate Symptom Score (IPSS), quality of life (QoL), postvoid residual volume (PVR), and maximum urinary flow rate (Qmax) were assessed. To control for selection bias, a 1:1 PS-matched analysis was carried out using the following variables as covariates: total prostate volume, preoperative IPSS and early sphincter release. RESULTS: Of 422 patients, 370 (87.7%) underwent ThuFLEP and 52 (12.3%) underwent bipolar enucleation. Operation, enucleation, and morcellation time were comparable between groups before and after PS-matched analysis (p=0.954, p=0.474, p=0.362, respectively). Functional parameters (IPSS, QoL, PVR, Qmax) were also comparable between groups at every time point before and after PS matching. Significant improvements in IPSS, QoL score, Qmax, and PVR were observed during the 24-month follow-up period for both ThuFLEP and bipolar enucleation without any significant differences between groups. Early and late postoperative complications before and after PS-matched analysis were similar. CONCLUSIONS: ThuFLEP was comparable to bipolar enucleation in perioperative characteristics, improvement in voiding parameters, and complication rates. Both procedures were shown to be effective and safe in the management of benign prostatic hyperplasia.

Skin dehydration monitoring with optical spectroscopy allows assessment of water content in the organism: Thermal and physical loads, diuretic therapy.

This study investigates the relationship between body hydration levels and skin hydration using spatially resolved diffuse reflectance spectroscopy. The research involved monitoring skin dehydration and rehydration under various conditions, including thermal and physical loads on healthy volunteers, and diuretic therapy in patients with edema syndrome. Findings indicate a correlation between body mass reduction and skin hydration: a 1% loss in body mass corresponds to a 10% decrease in skin hydration. During thermal stress, water absorption at 970 nm decreased monotonically without recovery. Physical activity resulted in approximately 10% changes in skin water content within 20 min, followed by rehydration. Patients with edema syndrome exhibited the most substantial decrease in water absorption amplitude, at nearly 30%, during diuretic treatment. These results support optical spectroscopy as a non-invasive tool for assessing body hydration, with implications for developing portable hydration monitoring devices for clinical and sports applications.

Predictors of microsurgical varicocelectomy efficacy in male infertility treatment: critical assessment and systematization.

In this review, we tried to systematize all the evidence (from PubMed [MEDLINE], Scopus, Cochrane Library, EBSCO, Embase, and Google Scholar) from 1993 to 2021 on the predictors of microsurgical varicocelectomy efficacy in male infertility treatment. Regarding the outcomes of varicocele repair, we considered semen improvement and pregnancy and analyzed them separately. Based on the 2011 Oxford CEBM Levels of Evidence, we assigned a score to each trial that studied the role of the predictor. We systematized the studied predictors based on the total points, which were, in turn, calculated based on the number and quality of studies that confirmed or rejected the studied predictor as significant, into three levels of significance: predictors of high, moderate, and low clinical significance. Preoperative total motile sperm count (TMSC) coupled with sperm concentration can be a significant predictor of semen improvement and pregnancy after varicocelectomy. In addition, for semen improvement alone, scrotal Doppler ultrasound (DUS) parameters, sperm DNA fragmentation index (DFI), and bilateral varicocelectomy are reliable predictors of microsurgical varicocelectomy efficacy.

Development of a Sensitive Digital Droplet PCR Screening Assay for the Detection of GPR126 Non-Coding Mutations in Bladder Cancer Urine Liquid Biopsies.

Recent whole-genome sequencing studies identified two novel recurrent mutations in the enhancer region of GPR126 in urothelial bladder cancer (UBC) tumor samples. This mutational hotspot is the second most common after the TERT promoter in UBC. The aim of the study was to develop a digital droplet PCR screening assay for the simultaneous detection of GPR126 mutations in a single tube. Its performance combined with TERT promoter mutation analysis was evaluated in urine of healthy volunteers (n = 50) and patients with cystitis (n = 22) and UBC (n = 70). The developed assay was validated using DNA constructs carrying the studied variants. None of the mutations were detected in control and cystitis group samples. GPR126 mutations were observed in the urine of 25/70 UBC patients (area under the ROC curve (AUC) of 0.679; mutant allele fraction (MAF) of 21.61 [8.30-44.52] %); TERT mutations-in 40/70 (AUC of 0.786; MAF = 28.29 [19.03-38.08] %); ≥1 mutation-in 47/70 (AUC of 0.836)). The simultaneous presence of GPR126 and TERT mutations was observed in 18/70 cases, with no difference in MAFs for the paired samples (31.96 [14.78-47.49] % vs. 27.13 [17.00-37.62] %, p = 0.349, respectively). The combined analysis of these common non-coding mutations in urine allows the sensitive and non-invasive detection of UBC.