Nanoribbon Biosensor-Based Detection of microRNA Markers of Prostate Cancer.

Prostate cancer (PC) is one of the major causes of death among elderly men. PC is often diagnosed later in progression due to asymptomatic early stages. Early detection of PC is thus crucial for effective PC treatment. The aim of this study is the simultaneous highly sensitive detection of a palette of PC-associated microRNAs (miRNAs) in human plasma samples. With this aim, a nanoribbon biosensor system based on "silicon-on-insulator" structures (SOI-NR biosensor) has been employed. In order to provide biospecific detection of the target miRNAs, the surface of individual nanoribbons has been sensitized with DNA oligonucleotide probes (oDNA probes) complementary to the target miRNAs. The lowest concentration of nucleic acids, detectable with our biosensor, has been found to be 1.1 × 10-17 M. The successful detection of target miRNAs, isolated from real plasma samples of PC patients, has also been demonstrated. We believe that the development of highly sensitive nanotechnology-based biosensors for the detection of PC markers is a step towards personalized medicine.

Development and Validation of an LC-MS/MS Method for Simultaneous Determination of Short Peptide-Based Drugs in Human Blood Plasma.

A novel HPLC-ESI-MS/MS method for simultaneous gonadotropin-releasing hormone (GnRH) analogs and somatostatin analog quantitation was developed and validated. The developed method was successfully applied to pharmacokinetic studies. The sample preparation process included solid-phase extraction (SPE). Effective chromatographic separation of the analytes and internal standard (dalargin) was achieved with a C18 column, using a gradient elution with two mobile phases: 0.1% v/v formic acid (aqueous solution) and 0.1% v/v formic acid (acetonitrile solution). The linearity of the method was demonstrated within a concentration range of 0.5-20 ng/mL, with correlation coefficients between 0.998-0.999 for goserelin, buserelin, triptorelin, and octreotide, respectively. The relative standard deviation (RSD, %) values for method accuracy and precision did not exceed 20% at the lower level of quantitation (LLOQ) or 15% at other concentration levels.

Prognostic role of the systemic immune-inflammation index in upper tract urothelial carcinoma treated with radical nephroureterectomy: results from a large multicenter international collaboration.

PURPOSE: To investigate the prognostic role of the preoperative systemic immune-inflammation index (SII) in patients with upper tract urothelial carcinoma (UTUC) treated with radical nephroureterectomy (RNU). MATERIALS AND METHODS: We retrospectively analyzed our multi-institutional database to identify 2492 patients. SII was calculated as platelet count × neutrophil/lymphocyte count and evaluated at a cutoff of 485. Logistic regression analyses were performed to investigate the association of SII with muscle-invasive and non-organ-confined (NOC) disease. Cox regression analyses were performed to investigate the association of SII with recurrence-free, cancer-specific, and overall survival (RFS/CSS/OS). RESULTS: Overall, 986 (41.6%) patients had an SII > 485. On univariable logistic regression analyses, SII > 485 was associated with a higher risk of muscle-invasive (P = 0.004) and NOC (P = 0.03) disease at RNU. On multivariable logistic regression, SII remained independently associated with muscle-invasive disease (P = 0.01). On univariable Cox regression analyses, SII > 485 was associated with shorter RFS (P = 0.002), CSS (P = 0.002) and OS (P = 0.004). On multivariable Cox regression analyses SII remained independently associated with survival outcomes (all P < 0.05). Addition of SII to the multivariable models improved their discrimination of the models for predicting muscle-invasive disease (P = 0.02). However, all area under the curve and C-indexes increased by < 0.02 and it did not improve net benefit on decision curve analysis. CONCLUSIONS: Preoperative altered SII is significantly associated with higher pathologic stages and worse survival outcomes in patients treated with RNU for UTUC. However, the SII appears to have relatively limited incremental additive value in clinical use. Further study of SII in prognosticating UTUC is warranted before routine use in clinical algorithms.

The Risk of New Onset Dementia and/or Alzheimer Disease among Patients with Prostate Cancer Treated with Androgen Deprivation Therapy: A Systematic Review and Meta-Analysis.

PURPOSE: Androgen deprivation therapy is a standard therapy for some patients with localized and almost all patients with metastatic prostate cancer. Although several clinical cohort studies have identified an impact of androgen deprivation therapy on cognitive function, the previous reviews were not able to perform a well designed quantitative synthesis to summarize the risk of dementia and/or Alzheimer disease. Consequently there is still a lack of systematic review and meta-analysis regarding the impact of this risk including more recent studies. MATERIALS AND METHODS: We conducted a systematic review and meta-analysis of the literature assessing the differential incidence of dementia and/or Alzheimer disease as outcomes in patients with prostate cancer who did vs did not receive androgen deprivation therapy. We queried PubMed® and Web of Science™ databases from January 1 to 3, 2020. We used random or fixed effects meta-analytic models in the presence or absence of heterogeneity per the I2 statistic. We performed 6 meta-analyses for all cause dementia, Alzheimer disease and all cause dementia or Alzheimer disease according to the duration of androgen deprivation therapy (up to 12 or more than 12 months). RESULTS: A total of 14 studies were selected after considering inclusion and exclusion criteria. Nine of them reported all cause dementia (ie all types of dementia including Alzheimer disease), with 8 reporting Alzheimer disease. Five studies assessed these outcomes according to the duration of androgen deprivation therapy. The risk of new onset dementia (all cause) and Alzheimer disease was higher in patients with prostate cancer who received androgen deprivation therapy compared to those who did not (HR 1.21, 95% CI 1.11-1.33 and HR 1.16, 95% CI 1.09-1.24). The risk of dementia (all cause) was higher in patients with prostate cancer who received androgen deprivation therapy for more than 12 months (HR 1.36, 95% CI 1.07-1.72); however, for those who had less than 12 months of androgen deprivation therapy exposure the difference was not statistically significant 1.06 (95% CI 0.77-1.28). There was no association between the androgen deprivation therapy duration and the risk of Alzheimer disease (HR 1.21, 95% CI 0.97-1.51 for exposure up to 12 months and HR 1.39, 95% CI 0.69-2.79 for exposure greater than 12 months). CONCLUSIONS: Men who receive androgen deprivation therapy for prostate cancer have an increased risk of dementia and/or Alzheimer disease compared to men who do not receive androgen deprivation therapy; this was more pronounced when androgen deprivation therapy was given longer than 12 months.

The recurrence and progression risk after simultaneous endoscopic surgery of urothelial bladder tumour and benign prostatic hyperplasia: a systematic review and meta-analysis.

OBJECTIVES: To evaluate recurrence and progression risk after simultaneous endoscopic surgery of bladder cancer and benign prostatic hyperplasia (BPH), as simultaneous surgery is not an unusual scenario and theoretically simultaneous transurethral resection of bladder tumour (TURBT) and transurethral resection of the prostate (TURP) can lead to an increased risk of recurrence in the bladder neck and prostatic urethra (BN/PU). METHODS: We conducted a systematic review and meta-analysis to assess the risk of recurrence (i.e. whole bladder and/or BN/PU) and tumour progression as outcomes after a simultaneous endoscopic surgery of bladder tumour and BPH, as compared to TURBT alone. We queried PubMed and Web of Science database on 1 January 2020. We used random- and/or fixed-effects meta-analytic models in the presence or absence of heterogeneity according to the I2 statistic, respectively. RESULTS: Nine retrospective and three clinical trial studies were selected after considering inclusion and exclusion criteria. We conducted the meta-analysis on retrospective and randomised controlled trials (RCTs) separately. Eight retrospective and three RCT studies were included to assess the BN/PU recurrence risk and the summarised risk ratio (RR) was 1.02 (95% confidence interval [CI] 0.74-1.41) and 0.93 (95% CI 0.47-1.84), respectively. Five retrospective and two RCT studies were included to assess the progression risk and the summarised RR was 0.91 (95% CI 0.56-1.48) and 1.16 (95% CI 0.30-4.51), respectively. Eight retrospective and three RCT studies were included to assess the whole bladder recurrence risk and the summarised RR was 0.87 (95% CI 0.78-0.97) and 0.89 (95% CI 0.65-1.21), respectively. CONCLUSION: We did not observe any increased risk of total bladder recurrence, BN/PU recurrence, or progression after a simultaneous endoscopic surgery of bladder tumour and BPH, as compared to TURBT alone.

Convolutional neural network in proteomics and metabolomics for determination of comorbidity between cancer and schizophrenia.

The association between cancer risk and schizophrenia is widely debated. Despite many epidemiological studies, there is still no strong evidence regarding the molecular basis for the comorbidity between these two pathological conditions. The vast majority of assays have been performed using clinical records of schizophrenic patients or those undergoing cancer treatment and monitored for sufficient time to find shared features between the considered conditions. We performed mass spectrometry-based proteomic and metabolomic investigations of patients with different cancer phenotypes (breast, ovarian, renal, and prostate) and patients with schizophrenia. The resulting vast quantity of proteomic and metabolomic data were then processed using systems biology and one-dimensional (1D) convolutional neural network (1DCNN) machine learning approaches. Traditional systematic approaches permit the segregation of schizophrenia and cancer phenotypes on the level of biological processes, while 1DCNN recognized "signatures" that could segregate distinct cancer phenotypes and schizophrenia at the comorbidity level. The designed network efficiently discriminated unrelated pathologies with a model accuracy of 0.90 and different subtypes of oncophenotypes with an accuracy of 0.94. The proposed strategy integrates systematic analysis of identified compounds and application of 1DCNN model for unidentified ones to reveal the similarity between distinct phenotypes.

Prognostic value of the preoperative albumin-globulin ratio in patients with upper urinary tract urothelial carcinoma treated with radical nephroureterectomy: results from a large multicenter international collaboration.

OBJECTIVE: To assess the value of preoperative albumin to globulin ratio for predicting pathologic and oncological outcomes in patients with upper tract urothelial carcinoma treated with radical nephroureterectomy in a large multi-institutional cohort. MATERIALS AND METHODS: Preoperative albumin to globulin ratio was assessed in a multi-institutional cohort of 2492 patients. Logistic regression analyses were performed to assess the association of the albumin to globulin ratio with pathologic features. Cox proportional hazards regression models were performed for survival endpoints. RESULTS: The optimal cut-off value was determined to be 1.4 according to a receiver operating curve analysis. Lower albumin to globulin ratios were observed in 797 patients (33.6%) compared with other patients. In a preoperative model, low preoperative albumin to globulin ratio was independently associated with nonorgan-confined diseases (odds ratio 1.32, P = 0.002). Patients with low albumin to globulin ratios had worse recurrence-free survival (P < 0.001), cancer-specific survival (P = 0.001) and overall survival (P = 0.020) in univariable and multivariable analyses after adjusting for the effect of standard preoperative prognostic factors (recurrence-free survival: hazard ratio (HR) 1.31, P = 0.001; cancer-specific survival: HR 1.31, P = 0.002 and overall survival: HR 1.18, P = 0.024). CONCLUSIONS: Lower preoperative albumin to globulin ratio is associated with locally advanced disease and worse clinical outcomes in patients treated with radical nephroureterectomy for upper tract urothelial carcinoma. As it is difficult to stage disease entity, low preoperative serum albumin to globulin ratio may help identify those most likely to benefit from intensified care, such as perioperative systemic therapy, and the extent and type of surgery.

Prognostic value of the pre-operative serum albumin to globulin ratio in patients with non-metastatic prostate cancer undergoing radical prostatectomy.

PURPOSE: To evaluate the potential predictive value of the preoperative serum albumin to globulin ratio (AGR) for oncological outcomes in patients treated with radical prostatectomy (RP) for clinically non-metastatic prostate cancer (PCa). METHODS: Pre-operative AGR was assessed in a multi-institutional cohort of 6041 patients treated with RP. Logistic regression analyses were performed to assess the association of the AGR with advanced disease. We performed Cox regression analyses to determine the relationship between AGR and biochemical recurrence (BCR). RESULTS: The optimal cut-off value was determined to be 1.31 according to receiver operating curve analysis. Compared to patients with a higher AGR, those with a lower preoperative AGR had worse BCR-free survival (P < 0.01) in the Kaplan-Meier analysis. Pre- and post-operative multivariable models that adjusted for the effects of established clinicopathologic features, confirmed its independent association with BCR [hazard ratio (HR) 1.52, 95% confidence interval (CI) 1.31-1.75, P < 0.01, HR 1.55, 95% CI 1.34-1.79, P < 0.01, respectively]. However, the addition of AGR to established prognostic models did not improve their discrimination. CONCLUSION: While AGR is significantly associated with BCR, in the present study, the clinical impact of AGR was not large enough to affect patient management. Longer follow-up is necessary to observe the true effect of AGR.

Micro-Raman Characterization of Structural Features of High-k Stack Layer of SOI Nanowire Chip, Designed to Detect Circular RNA Associated with the Development of Glioma.

The application of micro-Raman spectroscopy was used for characterization of structural features of the high-k stack (h-k) layer of "silicon-on-insulator" (SOI) nanowire (NW) chip (h-k-SOI-NW chip), including Al2O3 and HfO2 in various combinations after heat treatment from 425 to 1000 °C. After that, the NW structures h-k-SOI-NW chip was created using gas plasma etching optical lithography. The stability of the signals from the monocrine phase of HfO2 was shown. Significant differences were found in the elastic stresses of the silicon layers for very thick (>200 nm) Al2O3 layers. In the UV spectra of SOI layers of a silicon substrate with HfO2, shoulders in the Raman spectrum were observed at 480-490 cm-1 of single-phonon scattering. The h-k-SOI-NW chip created in this way has been used for the detection of DNA-oligonucleotide sequences (oDNA), that became a synthetic analog of circular RNA-circ-SHKBP1 associated with the development of glioma at a concentration of 1.1 × 10-16 M. The possibility of using such h-k-SOI NW chips for the detection of circ-SHKBP1 in blood plasma of patients diagnosed with neoplasm of uncertain nature of the brain and central nervous system was shown.

Prognostic Value of Variant Histology in Upper Tract Urothelial Carcinoma Treated with Nephroureterectomy: A Systematic Review and Meta-Analysis.

PURPOSE: We sought to assess the prognostic value of variant histology in patients with upper tract urothelial carcinoma treated with radical nephroureterectomy. MATERIALS AND METHODS: We searched PubMed®, Web of Science™, Cochrane Library and Scopus® databases in May 2019 according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement. Studies were deemed eligible if they compared overall, cancer specific and recurrence-free survival in patients with upper tract urothelial carcinoma with or without variant histology. Formal meta-analyses were performed for these outcomes. RESULTS: We identified 32 studies with 16,052 patients, including 26 studies with 12,865 patients that were eligible for the meta-analysis. Variant histology was associated with poor outcomes in terms of cancer specific (pooled HR 2.00, 95% CI 1.57 to 2.56), overall (pooled HR 1.76, 95% CI 1.51 to 2.04) and recurrence-free survival (pooled HR 1.64, 95% CI 1.42 to 1.89). Subgroup analyses revealed that micropapillary (pooled HR 3.02, 95% CI 1.71 to 5.34), and squamous and/or glandular variant histologies (pooled HR 1.48, 95% CI 1.14 to 1.92) were also associated with poor cancer specific survival. CONCLUSIONS: Variant histology in patients with upper tract urothelial carcinoma is associated with an increased risk of cancer specific and overall mortality and disease recurrence. Furthermore, variant histology was independently associated with cancer specific survival in the micropapillary, and squamous and/or glandular variant histology subgroups. It may be useful to incorporate variant histology into prognostic tools that help guide patients and physicians in selecting appropriate treatment strategies for upper tract urothelial carcinoma.

Differential Effect of Sex on Outcomes after Radical Surgery for Upper Tract and Bladder Urothelial Carcinoma: A Systematic Review and Meta-Analysis.

PURPOSE: We assessed the prognostic value of sex differences in upper tract urothelial carcinoma and urothelial carcinoma of the bladder treated with radical surgery. MATERIALS AND METHODS: The PubMed®, Web of Science®, Cochrane Library and Scopus® databases were searched in July 2019 according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. Studies were deemed eligible if they compared overall, cancer specific, and recurrence-free survival in patients with upper tract urothelial carcinoma and urothelial carcinoma of the bladder. Formal meta-analyses were performed for these outcomes according to sex differences. RESULTS: Overall 66 studies with 100,389 patients with urothelial carcinoma of the bladder and 40 studies with 39,759 patients with upper tract urothelial carcinoma were eligible for review and meta-analysis. Female patients with urothelial carcinoma of the bladder were associated with worse cancer specific survival (pooled HR 1.20, 95% CI 1.10-1.31), overall survival (pooled HR 1.03, 95% CI 1.01-1.05) and recurrence-free survival (pooled HR 1.13, 95% CI 1.02-1.25). In contrast, those with upper tract urothelial carcinoma were not associated with cancer specific survival (pooled HR 0.94, 95% CI 0.89-1.00), overall survival (pooled HR 0.98, 95% CI 0.95-1.01) and recurrence-free survival (pooled HR 0.90, 95% CI 0.78-1.03). CONCLUSIONS: Sex is associated with cancer specific mortality, overall mortality and disease recurrence in urothelial carcinoma of the bladder but not in upper tract urothelial carcinoma. Given the genetic and social differences between the sexes, sex differences may represent a key factor in the clinical decision making process.

En bloc resection for nonmuscle invasive bladder cancer: review of the recent literature.

PURPOSE OF REVIEW: Conventional transurethral resection of bladder tumor (cTURBT) is the standard approach to the diagnosis and treatment of nonmuscle invasive bladder cancer. However, it suffers from inherent limitations such as insufficient assessment of resection depth and the need for intravesical tumor fragmentation that hampers histopathological evaluation. We summarize recent clinical data on en bloc resection of bladder tumor (ERBT), a method that promises to overcome these limitations. RECENT FINDINGS: The PubMed/Medline databases were searched for reports on ERBT focusing on trends in the last 2 years. ERBT provides greater resection quality, making up to 95% of detrusor muscle available for pathological evaluation. ERBT also allows detection of the muscularis mucosae thus facilitating T1 substaging. Available data demonstrate no significant difference in perioperative morbidity. No conclusions can be drawn on the impact of either modality on tumor recurrence and progression, as the available data is too underpowered. SUMMARY: ERBT is gaining acceptances as there is increasing evidence that it improves the quality of resected specimens. There seems to be no difference in perioperative morbidity between ERBT and cTURBT. The impact of ERBT on important endpoints such as recurrence and progression remains to be fully elucidated in further studies.

The prognostic impact of tumour NSD2 expression in advanced prostate cancer.

Purpose: To assess the prognostic significance of the nuclear receptor binding SET protein 2 (NSD2), a co-activator of the NFkB-pathway, on tumour progression in patients with advanced prostate cancer (PCa).Methods: We retrospectively assessed NSD2 expression in 53 patients with metastatic and castration-resistant PCa. Immunohistochemical staining for NSD2 was carried out on specimen obtained from palliative resection of the prostate. Univariable and multivariable analyses were performed to assess the association between NSD2 expression and PCa progression.Results: Of the 53 patients, 41 had castration-resistant PCa and 48 men had metastases at time of tissue acquisition. NSD2 expression was increased in tumour specimen from 42 patients (79.2%). In univariable Cox regression analyses, NSD2 expression was associated with PSA progression, progression on imaging and overall survival (p = 0.04, respectively). In multivariable analyses, NSD2 expression did not retain its association with these endpoints.Conclusions: NSD2 expression is abnormal in almost 80% of patients with advanced PCa. Expression levels of this epigenetic regulator are easily detected by immunohistochemistry while this biomarker exhibited prognostic value for PCa progression and death in univariable analysis. Further studies on NSD2 involvement in PCa proliferation, progression, metastasis and resistance mechanisms are needed.

Prognostic value of alkaline phosphatase in hormone-sensitive prostate cancer: a systematic review and meta-analysis.

PURPOSE: To assess the prognostic value of alkaline phosphatase in patients with hormone-sensitive prostate cancer. METHODS: A systematic review and meta-analysis was performed using the PUBMED, Web of Science, Cochrane Library, and Scopus in April 2019 according to the Preferred Reporting Items for Systematic Review and Meta-analysis statement. Studies were deemed eligible if they compared hormone-sensitive prostate cancer patients with high vs. low alkaline phosphatase to determine its predictive value for overall survival, cancer-specific survival, and progression-free survival. We performed a formal meta-analysis of these outcomes. RESULTS: 42 articles with 7938 patients were included in the systematic review and 28 studies with 5849 patients for the qualitative assessment. High alkaline phosphatase was associated with worse overall survival (pooled HR 1.72; 95% CI 1.37-2.14) and progression-free survival (pooled HR 1.30; 95% CI 1.10-1.54). In subgroup analyses of patients with "high-volume" and "low-volume", alkaline phosphatase was associated with the overall survival (pooled HR 1.41; 95% CI 1.21-1.64 and pooled HR 1.64; 95% CI, 1.06-2.52, respectively). CONCLUSIONS: In this meta-analysis, elevated serum levels of alkaline phosphatase were associated with an increased risk of overall mortality and disease progression in patients with hormone-sensitive prostate cancer. In contrast, those were not associated with an increased risk of cancer-specific mortality. Alkaline phosphatase was independently associated with overall survival in both patients with "high-volume" and "low-volume" hormone-sensitive prostate cancer. Alkaline phosphatase may be useful for being integrated into prognostic tools that help guide treatment strategy, thereby facilitating the shared decision making process.

Revelation of Proteomic Indicators for Colorectal Cancer in Initial Stages of Development.

Background: Colorectal cancer (CRC) at a current clinical level is still hardly diagnosed, especially with regard to nascent tumors, which are typically asymptotic. Searching for reliable biomarkers of early diagnosis is an extremely essential task. Identification of specific post-translational modifications (PTM) may also significantly improve net benefits and tailor the process of CRC recognition. We examined depleted plasma samples obtained from 41 healthy volunteers and 28 patients with CRC at different stages to conduct comparative proteome-scaled analysis. The main goal of the study was to establish a constellation of protein markers in combination with their PTMs and semi-quantitative ratios that may support and realize the distinction of CRC until the disease has a poor clinical manifestation. Results: Proteomic analysis revealed 119 and 166 proteins for patients in stages I-II and III-IV, correspondingly. Plenty of proteins (44 proteins) reflected conditions of the immune response, lipid metabolism, and response to stress, but only a small portion of them were significant (p < 0.01) for distinguishing stages I-II of CRC. Among them, some cytokines (Clusterin (CLU), C4b-binding protein (C4BP), and CD59 glycoprotein (CD59), etc.) were the most prominent and the lectin pathway was specifically enhanced in patients with CRC. Significant alterations in Inter-alpha-trypsin inhibitor heavy chains (ITIH1, ITIH2, ITIH3, and ITIH4) levels were also observed due to their implication in tumor growth and the malignancy process. Other markers (Alpha-1-acid glycoprotein 2 (ORM2), Alpha-1B-glycoprotein (A1BG), Haptoglobin (HP), and Leucine-rich alpha-2-glycoprotein (LRG1), etc.) were found to create an ambiguous core involved in cancer development but also to exactly promote tumor progression in the early stages. Additionally, we identified post-translational modifications, which according to the literature are associated with the development of colorectal cancer, including kininogen 1 protein (T327-p), alpha-2-HS-glycoprotein (S138-p) and newly identified PTMs, i.e., vitamin D-binding protein (K75-ac and K370-ac) and plasma protease C1 inhibitor (Y294-p), which may also contribute and negatively impact on CRC progression. Conclusions: The contribution of cytokines and proteins of the extracellular matrix is the most significant factor in CRC development in the early stages. This can be concluded since tumor growth is tightly associated with chronic aseptic inflammation and concatenated malignancy related to loss of extracellular matrix stability. Due attention should be paid to Apolipoprotein E (APOE), Apolipoprotein C1 (APOC1), and Apolipoprotein B-100 (APOB) because of their impact on the malfunction of DNA repair and their capability to regulate mTOR and PI3K pathways. The contribution of the observed PTMs is still equivocal, but a significant decrease in the likelihood between modified and native proteins was not detected confidently.

Molecular Profiling of Athletes Performing High-Intensity Exercises in Extreme Environments.

The aim of this study was to determine the influence of high-intensity training under extreme conditions (T = 40 °C) on the metabolism and immunological reactions of athletes. Male triathletes (n = 11) with a high level of sports training performed load testing to failure (17 ± 2.7 min) and maximum oxygen consumption (64.1 ± 6.4 mL/min/kg). Blood plasma samples were collected before and immediately after exercise. Mass spectrometric metabolomic analysis identified 30 metabolites and 6 hormones in the plasma, of which 21 and 4 changed after exercise, respectively. Changes in the intermediate products of tricarboxylic and amino acids were observed (FC > 1.5) after exercise. The obtained data can be associated with the effect of physical activity on metabolism in athletes. Therefore, constant monitoring of the biochemical parameters of athletes can help coaches identify individual shortcomings in a timely manner and track changes, especially as the volume of training increases. In addition, it was revealed that the immunological reaction (manifestation of a hyperactive reaction to food components) is personalized in nature. Therefore, it is important for coaches and sports doctors to analyze and control the eating behavior of athletes to identify food intolerances or food allergies in a timely manner and develop an individual elimination diet.

The Efficacy and Safety of Relugolix Compared with Degarelix in Advanced Prostate Cancer Patients: A Network Meta-analysis of Randomized Trials.

CONTEXT: Degarelix is associated with high rates of injection site reaction. The US Food and Drug Administration approved relugolix, an oral gonadotropin-releasing hormone (GnRH) antagonist, for the treatment of advanced prostate cancer patients. OBJECTIVE: This systematic review and network meta-analysis aimed to compare the efficacy and safety of relugolix versus degarelix. EVIDENCE ACQUISITION: A systematic search was performed using major web databases for studies published before January 30, 2021, according to the Preferred Reporting Items for Systematic Review and Meta-analyses (PRISMA) extension statement for a network meta-analysis. Studies that compared the efficacy (12-mo castration rate with testosterone ≤50 ng/dl) and safety (adverse events [AEs]) of relugolix or degarelix and of the control group (GnRH agonists) were included. We used the Bayesian approach in the network meta-analysis. EVIDENCE SYNTHESIS: Four studies (n = 2059) met our eligibility criteria. The main efficacy analysis was conducted for two different treatments (relugolix and all doses of degarelix vs GnRH agonists); relugolix (risk ratio [RR] 1.09, 95% credible interval [CrI]: 0.95-1.23) and degarelix (RR 0.98, 95% CrI: 0.91-1.06) were not associated with different 12-mo castration rates. In the subgroup analysis, degarelix 480 mg was significantly associated with a lower castration rate (RR 0.46, 95% CrI: 0.07-0.92). In all efficacy ranking analyses, relugolix achieved the best rank. The safety analyses showed that relugolix (RR 0.99, 95% CrI: 0.6-1.6 and RR 0.72, 95% CrI: 0.4-1.3, respectively) and degarelix (RR 1.1, 95% CrI: 0.75-1.35 and RR 1.05, 95% CrI: 0.42-2.6, respectively) were not associated with either all AE or serious AE rates. In the ranking analyses, degarelix achieved the worst rank of all AEs and the best rank of serious AEs. Relugolix (RR 0.44, 95% CrI: 0.16-1.2) and degarelix (RR 0.74, 95% CrI: 0.37-1.52) were not associated with different cardiovascular event (CVE) rates; both were associated with lower CVE rates than GnRH agonists in the ranking analyses. CONCLUSIONS: We found that the efficacy and safety of relugolix are comparable with those of degarelix, albeit with no injection site reaction. Such data should be interpreted with caution until large-scale direct comparison studies with a longer follow-up are available. PATIENT SUMMARY: We found that relugolix, an oral gonadotropin-releasing hormone (GnRH) antagonist, has comparable efficacy and safety with degarelix, a parenteral GnRH antagonist, for the treatment of advanced prostate cancer patients.

Isolation of Circulating Tumor Cells from Seminal Fluid of Patients with Prostate Cancer Using Inertial Microfluidics.

Prostate cancer (PCa) diagnosis is primarily based on prostate-specific antigen (PSA) testing and prostate tissue biopsies. However, PSA testing has relatively low specificity, while tissue biopsies are highly invasive and have relatively low sensitivity at early stages of PCa. As an alternative, we developed a technique of liquid biopsy, based on isolation of circulating tumor cells (CTCs) from seminal fluid (SF). The recovery of PCa cells from SF was demonstrated using PCa cell lines, achieving an efficiency and throughput as high as 89% (±3.8%) and 1.7 mL min-1, respectively, while 99% (±0.7%) of sperm cells were disposed of. The introduced approach was further tested in a clinical setting by collecting and processing SF samples of PCa patients. The yield of isolated CTCs measured as high as 613 cells per SF sample in comparison with that of 6 cells from SF of healthy donors, holding significant promise for PCa diagnosis. The correlation analysis of the isolated CTC numbers with the standard prognostic parameters such as Gleason score and PSA serum level showed correlation coefficient values at 0.40 and 0.73, respectively. Taken together, our results show promise in the developed liquid biopsy technique to augment the existing diagnosis and prognosis of PCa.

Discordance Between Clinical and Pathological Staging and Grading in Upper Tract Urothelial Carcinoma.

INTRODUCTION: This study aimed to evaluate the concordance in tumor stage and grade between ureteroscopic (URS) biopsy and radical nephroureterectomy (RNU) in patients with upper tract urothelial carcinoma (UTUC). PATIENTS AND METHODS: Records of 1,214 UTUC patients who had undergone URS biopsy followed by RNU were included. Univariable and multivariable logistic regression analyses were performed to identify factors contributing to the pathological upstaging. RESULTS: The concordance between URS biopsy-based clinical and RNU pathological staging was 34.5%. Clinical understaging occurred in 59.5% patients. Upstaging to muscle-invasive disease occurred in 240 (41.7%) of 575 patients diagnosed with ≤cT1 disease. Of those diagnosed with muscle-invasive disease on final pathology, 89.6% had been clinically diagnosed with ≤cT1 disease. In the univariable analyses, computed tomography urography (CTU)-based invasion, ureter location, hydronephrosis, high-grade cytology, high-grade biopsy, sessile architecture, age, and women sex were significantly associated with pathological upstaging (P < .05). In the multivariable analyses, CTU-based invasion and hydronephrosis remained associated with pathological upstaging (P < .05). URS biopsy-based clinical and pathological gradings were concordant in 634 (54.2%) patients. Clinical undergrading occurred in 496 (42.4%) patients. CONCLUSIONS: Clinical understaging/undergrading and upstaging to muscle-invasive disease occurred in a high proportion of UTUC patients undergoing RNU. Despite the inherent selection bias, these data underline the challenges of accurate UTUC staging and grading. In daily clinical practice, URS biopsy and CTU offer the most accurate preoperative information albeit with limited predictive value when used alone. These findings should be considered when utilizing preoperative, risk-adapted strategies.

Nanoribbon Biosensor in the Detection of miRNAs Associated with Colorectal Cancer.

A nanoribbon biosensor (NRBS) was developed to register synthetic DNAs that simulate and are analogous to miRNA-17-3p associated with colorectal cancer. Using this nanoribbon biosensor, the ability to detect miRNA-17-3p in the blood plasma of a patient diagnosed with colorectal cancer has been demonstrated. The sensing element of the NRBS was a nanochip based on a silicon-on-insulator (SOI) nanostructure. The nanochip included an array of 10 nanoribbons and was designed with the implementation of top-down technology. For biospecific recognition of miRNA-17-3p, the nanochip was modified with DNA probes specific for miRNA-17-3p. The performance of the nanochip was preliminarily tested on model DNA oligonucleotides, which are synthetic analogues of miRNA-17-3p, and a detection limit of ~10-17 M was achieved. The results of this work can be used in the development of serological diagnostic systems for early detection of colorectal cancer.