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Background: Aldosterone-producing adenomas cause hypertension in 5–10 % of cases. Laparoscopic adrenalectomy is the gold standard treatment for early-stage adrenal gland tumors, but minimally invasive procedures, such as ablative techniques can also be applied. Therefore, we aimed to compare laparoscopic adrenalectomy and ablation techniques in terms of efficacy and safety in the treatment of benign adrenal gland tumors. Materials and methods: We conducted a systematic search in five databases and included studies comparing the efficacy and safety of ablation techniques and laparoscopic adrenalectomy. We calculated odds ratios (ORs) for eligible studies with binary outcomes, and mean differences (MD) with 95 % confidence intervals (CI) for continuous outcomes. Results: Five studies focusing on aldosterone-producing adenomas were included in our review. A total of 119 patients at 14 centers underwent ablation, and 161 patients had laparoscopic adrenalectomy. The complication rates (OR: 0.98, CI: 0.35–2.69) were similar in both groups, but among complications, hypertensive crisis (OR: 8.13; CI: 1.14–58.11) was more frequent in the ablative group, and even the success rate of interventions - the resolution of hypertension (OR: 0.30, CI: 0.16–0.56) - was lower in this group. On the other hand, the advantage of ablation was shorter intervention time (MD: 75.64 min; CI: 6.33–144.95), shorter hospital stay (MD: 1.6 days; CI: 0.88–2.31), and less perioperative blood loss (MD: 43.55 ml; CI: 12.07–75.04) compared to laparoscopy. Conclusion: Laparoscopic adrenalectomy is still the best therapeutic approach, but ablation can be an appropriate alternative option for the treatment of aldosterone-producing adrenal gland tumors.

Abstract Introduction Polycystic ovary syndrome (PCOS) is a common condition in women, characterised by reproductive and metabolic dysfunction. While dietary approaches have been evaluated as a first-line treatment for patients with PCOS, there is limited evidence to support preference for a specific dietary composition. This systematic review and network meta-analysis was performed with the objective of comparing different dietary interventions in terms of positive impact. Metformin, the currently preferred treatment, was also compared. Methods The latest systematic search was performed on the 20th of March, 2023. Eligible randomised controlled trials (RCTs) included patients with PCOS and compared the dietary approach with another intervention or a standard diet. Outcomes were expressed via anthropometric measurements and hormonal, glycemic, and lipid levels. The Bayesian method was used to perform a network meta-analysis and to calculate the surface under the cumulative ranking curve (SUCRA) values in order to rank the dietary interventions. The overall quality of the evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation system. Results 19 RCTs were identified, comprising data from 727 patients who were variously treated with 10 types of dietary interventions and metformin. The Dietary Approaches to Stop Hypertension (DASH) diet was the most effective in reducing Homeostatic Model Assessment of Insulin Resistance (SUCRA 92.33%), fasting blood glucose (SUCRA 85.92%), fasting insulin level (SUCRA 79.73%) and triglyceride level (SUCRA 82.07%). For body mass index (BMI), the most effective intervention was the low-calorie diet (SUCRA 84.59%). For weight loss, the low-calorie diet with metformin (SUCRA 74.38%) was the most effective intervention. Metformin produced the greatest reductions in low-density lipoprotein cholesterol (SUCRA 78.08%) and total testosterone levels (SUCRA 71.28%). The low-carb diet was the most effective intervention for reducing cholesterol levels (SUCRA 69.68%), while the normal diet (SUCRA 65.69%) ranked first for increasing high-density lipoprotein cholesterol levels. Conclusion Dietary interventions vary in their effects on metabolic parameters in women with PCOS. Based on our results, the DASH diet is the most effective dietary intervention for treating PCOS. Registration PROSPERO ID CRD42021282984

Abstract Background Ovarian cancer is the eighth leading cause of cancer-related death among women, characterized by late diagnosis and a high relapse rate. In randomized controlled trials, we aimed to evaluate the efficacy and safety of PARP inhibitors (PARPi) in treating advanced ovarian cancer. Methods This review was registered on PROSPERO (CRD42021283150), included all phase II and phase III randomized controlled trials (RCTs) assessing the effect of PARPi on ovarian cancer until the 13th of April, 2022. The main outcomes were progression- free survival (PFS), overall survival (OS), and adverse events (AEs). Pooled hazard ratios (HRs), and risk ratios (RRs) were calculated with 95% confidence intervals (95% CI). The random-effects model was applied in all analyses. Results In the meta-analysis, 16 eligible RCTs were included, with a total of 5,815 patients. In recurrent ovarian cancer, PARPi maintenance therapy showed a significant PFS benefit over placebo in the total population (HR 0.34, CI 0.29–0.40), BRCA mutant (HR 0.24, CI 0.18–0.31), germline BRCA mutant (HR 0.23, CI 0.18–0.30), and BRCA wild-type cases (HR 0.50, CI 0.39–0.65). PARPi monotherapy also improved PFS (HR 0.62, CI 0.51–0.76) compared with chemotherapy in BRCAm patients with recurrent ovarian cancer. The use of PARPi maintenance therapy resulted in an improvement in PFS over placebo in newly-diagnosed cancers in the overall population (HR 0.46, CI 0.30–0.71) and the BRCAm population (HR 0.36, CI 0.29–0.44). Although the risk of severe AEs was increased by PARPi therapy compared to placebo in most settings investigated, these side effects were controllable with dose modification, and treatment discontinuation was required in the minority of cases. Conclusions PARPis are an effective therapeutic option for newly-diagnosed and recurrent ovarian cancer. Despite a minor increase in the frequency of serious adverse effects, they are generally well tolerated.

Abstract Clinical trials revealed significant antitumor activity for immune checkpoint inhibitors (ICI) in metastatic urothelial carcinoma (mUC). Due to their strict eligibility criteria, clinical trials include selected patient cohorts, and thus do not necessarily represent real-world population outcomes. In this multicentric, retrospective study, we investigated real-world data to assess the effectiveness of pembrolizumab and atezolizumab and to evaluate the prognostic value of routinely available clinicopathological and laboratory parameters. Clinical and follow-up data from mUC patients who received ICIs (01/2017-12/2021) were evaluated. Overall survival (OS), progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and duration of response (DOR) were used as endpoints. Patients’ (n = 210, n = 76 atezolizumab and 134 pembrolizumab) median OS and PFS were 13.6 and 5.9 months, respectively. Impaired ECOG-PS, the presence of visceral, liver or bone metastases, and hemoglobin levels were independently associated with poor OS and DCR. Furthermore, Bellmunt risk factors and the enhanced Bellmunt-CRP score were shown to be prognostic for OS, PFS and DCR. In conclusion, ICIs are effective treatments for a broad range of mUC patients. Our results confirmed the prognostic value of numerous risk factors and showed that Bellmunt risk scores can further be improved when adding CRP to the model.

Abstract Prematurity is the leading cause of perinatal mortality and the morbidity among children under the age of 5. The prevalence of preterm birth is between 5 and 18% worldwide. Approximately 30% of preterm deliveries occur as a consequence of fetal or maternal infections. Bacterial vaginosis can increase the risk of ascending infections. However, there is no recommendation or protocol for screening of abnormal vaginal flora. The aim of this systematic review was to investigate the effectiveness of routine screening of abnormal vaginal flora during pregnancy care. We conducted our systematic search in the following databases: MEDLINE via PubMed, Embase, and Cochrane Library. Studies reporting on pregnant women with no symptoms of bacterial vaginosis were included in our analysis if they provided data on the outcome of their pregnancy. The intervention group went through screening of abnormal vaginal flora in addition to routine pregnancy care. Odds ratio (OR) with 95% confidence intervals (CIs) was used as effect size measure. From each study the total number of patients and number of events was extracted in both the intervention and control arm to calculate OR. Altogether we included 13 trials with 143,534 patients. The screening methods were Gram stain, pH screening, pH self-screening and pH screening combined with Gram stain. Regular screening of vaginal flora compared to no screening significantly reduces the odds of preterm birth before 37 weeks (8.98% vs 9.42%; OR 0.71, CI 0.57–0.87), birthweight under 2500 g (6.53% vs 7.24%; OR 0.64, CI 0.50–0.81), preterm birth before 32 weeks (1.35% vs 2.03%; OR 0.51, CI 0.31–0.85) and birthweight under 1000 g (0.86% vs 2.2%; OR 0.33, CI 0.19–0.57). In conclusion, the routine screening of abnormal vaginal flora might prevent preterm birth, extreme preterm birth, low birthweight deliveries and very low birthweight deliveries. Further research is needed to assess the problem more accurately.

The Mayo Adhesive Probability (MAP) score is a radiographic scoring system that predicts the presence of adherent perinephric fat (APF) during partial nephrectomies (PNs). The purpose of this systematic review is to summarize the current literature on the application of the MAP score for predicting intraoperative difficulties related to APF and complications in laparoscopic PNs. Three databases, PubMed, Scopus and Cochrane, were screened, from inception to 29 October 2023, taking into consideration the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Guidelines. All the inclusion criteria were met by eight studies. The total operative time was around two hours in most studies, while the warm ischemia time was

Introduction: Topical Imiquimod is an immune response modifier approved for the off-label use of vulvar intraepithelial neoplasia. We conducted this systematic review and meta-analysis to investigate the efficacy and safety of Imiquimod in treating cervical intraepithelial neoplasia (CIN) and human papillomavirus (HPV)-positive patients. Methods: The study was prospectively registered (CRD420222870) and involved a comprehensive systematic search of five medical databases on 10 October 2022. We included articles that assessed the use of Imiquimod in cervical dysplasia and HPV-positive patients. Pooled proportions, risk ratios (RRs), and corresponding 95% confidence intervals (CIs) were calculated using a random effects model to generate summary estimates. Statistical heterogeneity was assessed using I2 tested by the Cochran Q tests. Results: Eight articles reported on 398 patients who received Imiquimod out of 672 patients. Among CIN-2–3 patients, we observed a pooled regression rate of 61% (CI: 0.46–0.75; I2: 77%). When compared, Imiquimod was inferior to conization (RR: 0.62; CI: 0.42–0.92; I2: 64%). The HPV clearance rate in women who completed Imiquimod treatment was 60% (CI: 0.31–0.81; I2: 57%). The majority of side effects reported were mild to moderate in severity. Conclusions: Our findings indicate that topical Imiquimod is safe and effective in reducing cervical intraepithelial neoplasia and promoting HPV clearance. However, it was found to be inferior compared to conization. Imiquimod could be considered a potential medication for high-grade CIN patients and should be incorporated into guidelines for treating cervical dysplasia.

Abstract Background Metformin is the gold standard insulin sensitizer, which is widely used to treat insulin resistance in polycystic ovary syndrome (PCOS). However, metformin may induce gastrointestinal side effects. Objective Inositols have long been debated as a potential alternative for metformin in treating PCOS. Therefore, the present systematic review aimed to evaluate the efficacy and safety of inositols in treating PCOS. Methods The present systematic search was performed in CENTRAL, MEDLINE, and Embase from the inception until October 20th, 2021. Eligible randomized controlled trials (RCTs) included women diagnosed with PCOS and compared any inositols with metformin or placebo. Our primary outcome was cycle normalization, whereas secondary outcomes were body mass index (BMI), parameters of carbohydrate metabolism and clinical and laboratory hyperandrogenism. Results are reported as risk ratios or mean differences (MDs) with 95% confidence intervals (CIs). Results Twenty-six RCTs were identified, including data of 1691 patients (806 inositol, 311 with placebo, and 509 metformin groups). In patients treated with inositols, the risk (CI: 1.13; 2.85) of having a regular menstrual cycle was found by 1.79 higher than in the case of placebo. Moreover, the inositols showed non-inferiority compared to metformin in this outcome. In the case of BMI (MD = -0.45; CI: -0.89; -0.02), free testosterone (MD = -0,41, CI: -0.69; -0.13), total testosterone (MD = -20.39, CI: -40.12; -0.66), androstenedione (MD = -0.69, CI: -1,16; -0.22), glucose (MD = -3.14; CI: -5.75; -0.54) levels and AUC insulin (MD = -2081.05, CI: -2745.32; -1416.78) inositol treatment induced greater decrease compared to placebo. Inositol increased sex-hormone-binding globulin significantly compared to placebo (MD = 32.06, CI:1.27; 62.85). Conclusion Inositol is an effective and safe treatment in PCOS. Moreover, inositols showed non-inferiority in most outcomes compared to the gold standard treatment; metformin. Trial registration PROSPERO registration number: CRD42021283275.

Abstract Introduction Infertility affects one in every six couples in developed countries, and approximately 50% is of male origin. In 2021, sperm DNA fragmentation (SDF) testing became an evidence-based test for fertility evaluations depicting fertility more clearly than standard semen parameters. Therefore, we aimed to summarize the potential prognostic factors of a higher SDF. Methods We conducted a systematic search in three medical databases and included studies investigating any risk factors for SDF values. We calculated mean differences (MD) in SDF with 95% confidence interval (CI) for exposed and non-exposed individuals. Results We included 190 studies in our analysis. In the group of associated health conditions, varicocele (MD = 13.62%, CI: 9.39–17.84) and impaired glucose tolerance (MD = 13.75%, CI: 6.99–20.51) had the most significant increase in SDF. Among malignancies, testicular tumors had the highest impact, with a maximum of MD = 11.3% (CI: 7.84–14.76). Among infections, the overall effects of both Chlamydia and HPV were negligible. Of lifestyle factors, smoking had the most disruptive effect on SDF – an increase of 9.19% (CI: 4.33–14.06). Different periods of sexual abstinence did not show significant variations in SDF values. Age seemed to have a more drastic effect on SDF from age 50 onwards, with a mean difference of 12.58% (CI: 7.31–17.86). Pollution also had a detrimental effect – 9.68% (CI: 6.85–12.52). Conclusion Of the above risk factors, varicocele, impaired glucose tolerance, testicular tumors, smoking, pollution, and paternal age of over 50 were associated with the highest SDF. Trial registration CRD42021282533.

Although gestational diabetes mellitus (GDM) has several short- and long-term adverse effects on the mother and the offspring, no medicine is generally prescribed to prevent GDM. The present systematic review and meta-analysis aimed to investigate the effect of inositol supplementation in preventing GDM and related outcomes. Systematic search was performed in CENTRAL, MEDLINE, and Embase until 13 September 2023. Eligible randomized controlled trials (RCTs) compared the efficacy of inositols to placebo in pregnant women at high risk for GDM. Our primary outcome was the incidence of GDM, whereas secondary outcomes were oral glucose tolerance test (OGTT) and maternal and fetal complications. (PROSPERO registration number: CRD42021284939). Eight eligible RCTs were identified, including the data of 1795 patients. The incidence of GDM was halved by inositols compared to placebo (RR = 0.42, CI: 0.26–0.67). Fasting, 1-h, and 2-h OGTT glucose levels were significantly decreased by inositols. The stereoisomer myoinositol also reduced the risk of insulin need (RR = 0.29, CI: 0.13–0.68), preeclampsia or gestational hypertension (RR = 0.38, CI: 0.2–0.71), preterm birth (RR = 0.44, CI: 0.22–0.88), and neonatal hypoglycemia (RR = 0.12, CI: 0.03–0.55). Myoinositol decrease the incidence of GDM in pregnancies high-risk for GDM. Moreover, myoinositol supplementation reduces the risk of insulin need, preeclampsia or gestational hypertension, preterm birth, and neonatal hypoglycemia. Based on the present study 2–4 g myoinositol canbe suggested from the first trimester to prevent GDM and related outcomes.

Lymph node (LN) status is the most significant prognostic factor for invasive urothelial bladder cancer (UBC); however, the optimal extent of LN dissection (LND) is debated. We assessed circulating matrix metalloproteinase-7 (MMP-7) as a prognostic factor and decision-making marker for the extent of LND. Preoperative serum MMP-7 levels were determined in two independent UBC cohorts (n = 188; n = 68) and in one control cohort (n = 97) by using the ELISA method. A systematic review and meta-analysis on the prognostic role of circulating pretreatment MMP-7 levels were performed. Serum MMP-7 levels were higher in patients compared to controls (p < 0.001) with the highest levels in LN-positive cases. Half of LN-positive UBC patients had low MMP-7 levels, whereas the survival of LN-negative patients with high serum MMP-7 findings was poor. MMP-7 levels were independently associated with poor survival in both cohorts (p = 0.006, p < 0.001). Accordingly, our systematic review of six eligible publications revealed a 2.5-fold higher mortality risk in patients with high MMP-7 levels. In conclusion, preoperative MMP-7 level is a validated and independent prognostic factor in urothelial cancer. It cannot be used to decide between regional or extended LND but may be useful in identifying LN-negative high-risk patients with potentially undetected metastases.

Clear cell renal carcinoma is the most frequent type of kidney cancer, with an increasing incidence rate worldwide. In this research, we used a proteotranscriptomic approach to differentiate normal and tumor tissues in clear cell renal cell carcinoma (ccRCC). Using transcriptomic data of patients with malignant and paired normal tissue samples from gene array cohorts, we identified the top genes over-expressed in ccRCC. We collected surgically resected ccRCC specimens to further investigate the transcriptomic results on the proteome level. The differential protein abundance was evaluated using targeted mass spectrometry (MS). We assembled a database of 558 renal tissue samples from NCBI GEO and used these to uncover the top genes with higher expression in ccRCC. For protein level analysis 162 malignant and normal kidney tissue samples were acquired. The most consistently upregulated genes were IGFBP3, PLIN2, PLOD2, PFKP, VEGFA, and CCND1 (p < 10−5 for each gene). Mass spectrometry further validated the differential protein abundance of these genes (IGFBP3, p = 7.53 × 10−18; PLIN2, p = 3.9 × 10−39; PLOD2, p = 6.51 × 10−36; PFKP, p = 1.01 × 10−47; VEGFA, p = 1.40 × 10−22; CCND1, p = 1.04 × 10−24). We also identified those proteins which correlate with overall survival. Finally, a support vector machine-based classification algorithm using the protein-level data was set up. We used transcriptomic and proteomic data to identify a minimal panel of proteins highly specific for clear cell renal carcinoma tissues. The introduced gene panel could be used as a promising tool in the clinical setting.

Background/Purpose: Rapid hemostasis, an essential prerequisite of good surgical practice during surgical bleeding, including soft tissue open surgery, often requires adjunctive treatment. We evaluated the safety and hemostatic effectiveness of a human plasma-derived fibrin sealant (FS Grifols) in soft tissue open surgery. Methods: Patients with moderate soft tissue bleeding during open, urologic, gynecologic or general surgery were studied. The trial consisted of a preliminary phase (to familiarize investigators with the technique for FS Grifols application and the intraoperative procedures required by the clinical protocol) and a primary phase: in both phases, patients were randomized 1:1 to FS Grifols or Surgicel®. The primary efficacy endpoint, based on analysis of subjects in the primary phase of the study, was to evaluate whether FS Grifols was non-inferior to Surgicel® in achieving hemostasis, based on the proportion of subjects in both treatment groups who achieved hemostasis at the target bleeding site (TBS) by 4 min (T4) following the start of treatment application. Safety assessments included adverse events (AEs), vital signs, physical assessments, common clinical laboratory tests, viral markers, and immunogenicity. Results: A total of 224 subjects were randomized (primary phase): FS Grifols (N = 116), Surgicel® (N = 108). The 95% CI at T4 for the ratio of the proportion of patients achieving hemostasis in the two treatment groups was 1.064 (0.934, 1.213), indicating non-inferiority for FS Grifols vs. Surgicel®. The rate of hemostasis at the TBS by T4 in both phases of the study was higher in the FS Grifols treatment group (preliminary phase: 90.2%; primary phase: 82.8%) than in the Surgicel® treatment group (preliminary phase: 78.8%; primary phase: 77.8%). Overall, reported AEs were as expected in surgical patients and were similar between the two treatment groups. Conclusions: This study shows the non-inferiority in time to hemostasis of FS Grifols vs. Surgicel as an adjunct to hemostasis in patients undergoing soft tissue open surgery, and a similar rate of AEs.

Bradykinin (BK) has been proposed to modulate urinary bladder functions and implicated in the pathophysiology of detrusor overactivity. The present study aims to elucidate the signaling pathways of BK-induced detrusor muscle contraction, with the goal of better understanding the molecular regulation of micturition and identifying potential novel therapeutic targets of its disorders. Experiments have been carried out on bladders isolated from wild-type or genetically modified [smooth muscle-specific knockout (KO): Gαq/11-KO, Gα12/13-KO and constitutive KO: thromboxane prostanoid (TP) receptor-KO, cyclooxygenase-1 (COX-1)-KO] mice and on human bladder samples. Contractions of detrusor strips were measured by myography. Bradykinin induced concentration-dependent contractions in both murine and human bladders, which were independent of secondary release of acetylcholine, ATP, or prostanoid mediators. B2 receptor antagonist HOE-140 markedly diminished contractile responses in both species, whereas B1 receptor antagonist R-715 did not alter BK's effect. Consistently with these findings, pharmacological stimulation of B2 but not B1 receptors resembled the effect of BK. Interestingly, both Gαq/11- and Gα12/13-KO murine bladders showed reduced response to BK, indicating that simultaneous activation of both pathways is required for the contraction. Furthermore, the Rho-kinase (ROCK) inhibitor Y-27632 markedly decreased contractions in both murine and human bladders. Our results indicate that BK evokes contractions in murine and human bladders, acting primarily on B2 receptors. Gαq/11-coupled and Gα12/13-RhoA-ROCK signaling appear to mediate these contractions simultaneously. Inhibition of ROCK enzyme reduces the contractions in both species, identifying this enzyme, together with B2 receptor, as potential targets for treating voiding disorders.

Programmed death ligand-1 (PD-L1) is an immune checkpoint molecule and a widely used therapeutic target in urothelial cancer. Its circulating, soluble levels (sPD-L1) were recently suggested to be associated with the presence and prognosis of various malignancies but have not yet been investigated in upper tract urothelial carcinoma (UTUC). In this study, we assessed sPD-L1 levels in 97 prospectively collected serum samples from 61 UTUC patients who underwent radical nephroureterectomy (RNU), chemotherapy (CTX), or immune checkpoint inhibitor (ICI) therapy. In addition to pretreatment samples, postoperative and on-treatment sPD-L1 levels were determined in some patients by using ELISA. In the RNU group, elevated preoperative sPD-L1 was associated with a higher tumor grade (p = 0.019), stage (p < 0.001) and the presence of metastasis (p = 0.002). High sPD-L1 levels were significantly associated with worse survival in both the RNU and CTX cohorts. sPD-L1 levels were significantly elevated in postoperative samples (p = 0.011), while they remained unchanged during CTX. Interestingly, ICI treatment caused a strong, 25-fold increase in sPD-L1 (p < 0.001). Our results suggest that elevated preoperative sPD-L1 level is a predictor of higher pathological tumor stage and worse survival in UTUC, which therefore may help to optimize therapeutic decision-making. The observed characteristic sPD-L1 flare during immune checkpoint inhibitor therapy may have clinical significance.

Progression of non-muscle-invasive bladder cancer (NMIBC) to muscle-invasive disease (MIBC) significantly worsens life expectancy. Its risk can be assessed by clinicopathological factors according to international guidelines. However, additional molecular markers are needed to refine and improve the prediction. Therefore, in the present study, we aimed to predict the progression of NMIBCs to MIBC by assessing p53 expression, polysomy of chromosome 17 (Chr17) and HER2 status in the tissue specimens of the tumors of 90 NMIBC patients. Median follow-up was 77 months (range 2–158). Patients with Chr17 polysomy or HER2 gene amplification had a higher rate of disease progression (hazard ratio: 7.44; p < 0.001 and 4.04; p = 0.033, respectively; univariate Cox regression). Multivariable Cox regression models demonstrated that the addition of either Chr17 polysomy or HER2 gene amplification status to the European Association of Urology (EAU) progression risk score increases the c-index (from 0.741/EAU/ to 0.793 and 0.755, respectively), indicating that Chr17 polysomy/HER2 amplification status information improves the accuracy of the EAU risk table in predicting disease progression. HER2/Chr17 in situ hybridization can be used to select non-progressive cases not requiring strict follow-up, by reclassifying non-HER2-amplified, non-polysomic NMIBCs from the high- and very high-risk groups of EAU to the intermediate-risk group.

Recently, a neuroendocrine-like molecular subtype has been discovered in muscle-invasive urothelial bladder cancer (BC). Chromogranin A (CGA) is a widely used tissue and serum marker in neuroendocrine tumors. Our aim was to evaluate serum CGA (sCGA) concentrations and their associations with clinical and follow-up data in BC and renal cell carcinoma (RCC). sCGA concentrations were analyzed in the following cohorts: (1) BC training set (n = 188), (2) BC validation set (n = 125), (3) RCC patients (n = 77), (4) healthy controls (n = 97). CGA immunohistochemistry and RT-qPCR analyses were performed in 20 selected FFPE and 29 frozen BC tissue samples. Acquired data were correlated with clinicopathological parameters including comorbidities with known effect on sCGA as well as with patients’ follow-up data. sCGA levels were significantly higher in BC but not in RCC patients compared to healthy controls. High sCGA levels were independently associated with poor overall and disease-specific survival both in the BC training (P < 0.001, P = 0.002) and validation set (P = 0.009, P = 0.017). sCGA levels were inversely correlated with glomerulus filtrating rate (GFR) and linearly correlated with creatinine clearance and urea concentrations. These correlations were not related to the prognostic value of sCGA. Tissue CGA levels were low to absent independently of sCGA concentrations. Our results demonstrate elevated levels and an independent prognostic value for sCGA in BC but not in RCC. Despite the significant correlation between sCGA and GFR, the prognostic relevance of sCGA seems not related to impaired renal function or other comorbidities.

Upper tract urothelial carcinoma (UTUC) is a rare cancer with a barely predictable clinical behaviour. Serum MMP-7 is a validated prognostic marker in urothelial bladder cancer, a tumour entity with large clinical, histological, and molecular similarity to UTUC. The serum MMP-7 levels have not yet been investigated in UTUC. In the present study, we determined MMP-7 concentrations in an overall number of 103 serum samples from 57 UTUC patients who underwent surgical or systemic (platinum or immune checkpoint inhibitor) therapy by using the ELISA method. In addition to pre-treatment samples, the serum samples collected at predefined time points after or during therapy were also investigated. Serum MMP-7 concentrations were correlated with clinicopathological and follow-up data. Our results revealed significantly, two-fold elevated pre-treatment serum MMP-7 levels in metastatic cases of UTUC in both the radical surgery- and the chemotherapy-treated cohorts (p = 0.045 and p = 0.040, respectively). In addition, high serum MMP-7 levels significantly decreased after radical surgery, and high pre-treatment MMP-7 concentrations were associated with shorter survival both in the surgery- and chemotherapy-treated cohorts (p = 0.029 and p = 0.001, respectively). Our results revealed pre-treatment serum MMP-7 as a prognostic marker for UTUC, which may help to improve preoperative risk-stratification and thereby improve therapeutic decision-making.

While family history (FHx) of prostate cancer (PCa) increases the risk of PCa, comparably less is known regarding the impact of FHx on pathologic and oncologic outcomes after radical prostatectomy (RP). We retrospectively reviewed our multicenter database comprising 6,041 nonmetastatic PCa patients treated with RP. Patients with a FHx of PCa in one or more first-degree relatives were considered as FHx positive. We examined the association of FHx with pathologic outcomes and biochemical recurrence (BCR) using logistic and Cox regression models, respectively. In total, 1,677 (28%) patients reported a FHx of PCa. Compared to patients without FHx, those with, were younger at RP (median age of 59 vs. 62 years, p < 0.01), and had significantlymore favorable biopsy and RP histopathologic findings. On multivariable logistic regression analysis, positive FHx was associated with extracapsular extension (odds ratio [OR] 0.77, 95% confidence interval [CI] 0.66–0.90, p < 0.01; model AUC 0.73) and upgrading (OR 0.70, 95% CI 0.62–0.80, p < 0.01; model AUC 0.68). Incorporating FHx significantly improved the AUC of the base model for upgrading (p < 0.01). Positive FHx was not associated with BCR in pre- and postoperative multivariable models (p = 0.1 and p = 0.7); c-indexes of Cox multivariable models were: 0.73 and 0.82, respectively. We found that patients with clinically nonmetastatic PCa who have positive FHx of PCa undergo RP at a younger age and have more favorable pathologic outcomes. Nevertheless, FHx of PCa did not confer better BCR rates, suggesting that FHx leads to potentially early detection and treatment without impact on BCR. [ABSTRACT FROM AUTHOR]

Post orgasmic illness syndrome is a rare, mysterious condition with an unknown pathomechanism and uncertain treatment. The symptoms of post orgasmic illness syndrome last about 2–7 days after an ejaculation. The current hypothesis proposes that the primary injury in post orgasmic illness syndrome is an acute compression proprioceptive axonopathy in the muscle spindle, as is suspected in delayed onset muscle soreness. The terminal arbor degeneration-like lesion of delayed onset muscle soreness is theorized to be an acute stress response energy-depleted dysfunctional mitochondria-induced impairment of Piezo2 channels and glutamate vesicular release. The recurring symptoms of post orgasmic illness syndrome after each ejaculation are suggested to be analogous to the repeated bout effect of delayed onset muscle soreness. However, there are differences in the pathomechanism, mostly attributed to the extent of secondary tissue damage and to the extent of spermidine depletion. The spermidine depletion-induced differences are as follows: modulation of the acute stress response, flu-like symptoms, opioid-like withdrawal and enhanced deregulation of the autonomic nervous system. The longitudinal dimension of delayed onset muscle soreness, in the form of post orgasmic illness syndrome and the repeated bout effect, have cognitive and memory consequences, since the primary injury is learning and memory-related.

Reviewed by Kenneth Nyirády