Prospective Longitudinal Health-related Quality of Life Analysis of the Finnish Arm of the PRIAS Active Surveillance Cohort : 11 Years of Follow-up

Publisher Copyright: © 2021Background: Living with an untreated cancer may alter quality of life (QoL) in the long term. Objective: To prospectively study long-term changes in general, mental, and physical QoL in a contemporary active surveillance (AS) patient cohort with low-risk prostate cancer (PCa). Design, setting, and participants: The study population consisted of patients enrolled in the PRIAS trial in Helsinki University Hospital (n = 348). The RAND-36 questionnaire was used to assess general QoL at the start of AS and at 1, 3, 5, 7, 9, and 11 years during follow-up. Patients who had undergone robot-assisted laparoscopic prostatectomy (RALP; n = 88) also received the questionnaire after treatment. Outcome measurements and statistical analysis: Changes over time were analysed using multilevel mixed-effects regression models, and reported as the mean and95% confidence interval. A rule of 0.5 × standard deviation was used to estimate changes of clinical importance. Results and limitations: Median follow-up until the end of AS or last follow-up was 7.2 (range 0.3−12.7) yr. A decrease was observed in six of eight QoL subdomains at 7 yr. However, all scores were above age-stratified reference values. There was no difference between the group who continued AS throughout the study period and the group who discontinued AS and underwent RALP. More than half of the study cohort discontinued AS (n = 198; 57%), 135 men (68%) because of events specified in the protocol and only seven (3.5%) because of anxiety. Metastatic disease developed in six patients (1.7%), and two cases (0.6%) of PCa-related death were recorded among 348 patients in more than 12 yr of overall follow-up. The lack of a randomised control population is a limitation of the study. Conclusions: Contemporary protocolised AS does not impair general QoL. Men undergoing a treatment change (RALP) did not experience a decrease in QoL before or after their treatment change. Patient summary: Active surveillance is a safe treatment option for men with low-risk prostate cancer. We show that this follow-up strategy does not cause a decline in patients’ general quality of life.Peer reviewe

Expression levels of maternal plasma microRNAs in preeclamptic pregnancies

The present study aimed to identify the differential expression profiles of microRNAs in the plasma between patients with preeclampsia (PE) and healthy pregnancies using quantitative real-time PCR. The expression profiles of 32 miRNAs in maternal plasma from 31 patients with PE and 32 healthy pregnancies were evaluated. The expression levels of eight miRNAs including miR-210, miR-375, miR-197-3p, miR-132-3p, miR-29a-3p, miR-328, miR-24-3p, and miR-218-5p were significantly upregulated and the expression levels of three miRNAs, including miR-302b-3p, miR-191-5p, and miR-17-5p, were significantly downregulated in patients with preeclampsia when compared to healthy pregnant women. In conclusion, we identified 11 miRNAs that may be potential biomarkers for non-invasive diagnosis and a pivotal role in the prediction of PE. Considering the small cohort of patients, further studies with larger samples from different gestational stages are necessary to confirm our findings.IMPACT STATEMENT What is already known on this subject? The alterations in the release pattern of placenta-specific miRNAs detected in maternal serum have been found to be associated with pregnancy-related complications such as preeclampsia (PE). What do the results of this study add? In the present study, the release pattern of seven miRNAs had consistency and two of them had inconsistency with previous researches. Moreover, two novel miRNAs were also defined to demonstrate the interrelationship between PE and miRNAs. What are the implications of these findings for clinical practice and/or future research? The identification of 11 miRNAs that may be potential biomarkers for non-invasive diagnosis and a pivotal role in the prediction of PE. Considering the small cohort of patients, further studies with larger samples from different gestational stages are necessary to confirm our findings

Hydrocalyx: Uncommon Complication of Percutaneous Nephrolithotomy

The success rate of percutaneous nephrolithotomy (PNL) is about 90%, but overall complications of this surgery have been reported in up to 83% cases. The complications are graded using Clavien classification system from grade 1 to 5. Grade 1 needs simple treatments without surgical, endoscopic, and radiologic interventions like antiemetics, antipyretics, and analgesics. Grade 5 denotes death of the patient. Calyx neck stricture is grade 3b complication with an incidence of 0.1%. In this study, a case of hydrocalyx, which is very rare complication after PNL, is presented. To the best of the authors' knowledge, there is no hydrocalyx case reported after PNL in the literature

PTEN Loss but Not ERG Expression in Diagnostic Biopsies Is Associated with Increased Risk of Progression and Adverse Surgical Findings in Men with Prostate Cancer on Active Surveillance

Background Active surveillance (AS) is an option for men with low-risk prostate cancer (PCa). PTEN and ERG have been considered as potential biomarkers of PCa progression and survival. Objective To study the role of ERG and PTEN status in the Prostate Cancer Research International: Active Surveillance (PRIAS) trial diagnostic biopsies (DBxs) in predicting surveillance discontinuation and adverse surgical findings in subsequent radical prostatectomy (RP). Design, setting, and participants A total of 231 patients were recruited to the PRIAS between 2007 and 2013 in Helsinki. DBx tissue for immunohistochemistry (IHC) was available from 190 patients. Tissue microarrays (TMAs) were constructed from 57 specimens of subsequent RPs. DBxs containing grade group (GG) 1 PCa and RP TMA sections were stained with ERG and PTEN antibodies, and scored as either negative or positive. Outcome measurements and statistical analyses Outcomes were followed up by biopsy GG upgrade (GG ≥ 2) and protocol-based treatment change, as well as adverse findings in RP (GG ≥ 3 or pathological stage ≥ 3). Clinical variables and biomarker status in DBx were correlated in Cox regression analysis and cumulative survival in Kaplan–Meier analysis, and finally, Gray’s competing risk analysis was performed and nonprotocol-based discontinuation was considered as a competing event. Results and limitations In both uni- and multivariate Cox regression analyses, only the number of positive cores in the DBx, the number of rebiopsy sessions, and PTEN status at diagnosis were significantly associated with rebiopsy GG upgrade, treatment change, and adverse histopathology in RP. In Kaplan–Meier analysis, PTEN loss was associated with a shorter time to GG upgrade and treatment change. Patients with PTEN loss had a higher probability for protocol-based discontinuation but not for competing risk factors compared with patients with intact PTEN. Biopsy ERG status was concordant with RP TMA ERG status, while PTEN was not. Limitations include a retrospective analysis of prospective cohort data. Conclusions PTEN status at diagnosis is a potential biomarker for identifying patients with PCa on AS with a high risk for progression or adverse findings on subsequent RP. Patient summary A simple diagnostic biopsy-based analysis of PTEN status may help identify patients with high risk for prostate cancer progression. Keywords PTEN; ERG; Immunohistochemistry; Biopsy; Active surveillancePeer reviewe

Evaluation of combined therapeutic effects of hydrogen sulfide donor sodium hydrogen sulfide and phosphodiesterase type-5 inhibitor tadalafil on erectile dysfunction in a partially bladder outlet obstructed rat model

Aims: To evaluate the impacts of hydrogen sulfide (H2S) donor, sodium hydrogen sulfide (NaHS), and phosphodiesterase type-5 inhibitor (PDE5i), tadalafil per se and their combination treatment on partial bladder outlet obstruction (PBOO)-induced erectile dysfunction (ED). Methods: Sprague-Dawley rats were equally divided into five groups: (a) sham-operated control; (b) PBOO; (c) PBOO-treated with NaHS (5.6 mg/kg/day, ip); (d) PBOO-treated with tadalafil (2 mg/kg/day, oral); and (e) PBOO-treated with combination of NaHS and tadalafil. The obstruction was created by urethral ligation for 6 weeks. In vivo erectile responses, in vitro relaxant and contractile responses in penile tissue as well as protein expression of nitric oxide synthases (NOS), H2S synthesis enzymes, oxidative stress, hypoxia, fibrosis markers, and the smooth muscle/collagen ratio and apoptosis were analyzed. Results: Combined treatment entirely returned increased bladder mass, reduced erectile responses, relaxation responses to acetylcholine, and electrical field stimulation in obstructed rats, while partial amelioration was observed after mono-treatment. Decreased neuronal NOS and 3-mercaptopiruvate transferase enzyme expressions in penile tissue from obstructed rats were also entirely restored by the combined treatment. Mono-treatment partially improved increased hypoxia, oxidative stress, fibrosis markers, decreased smooth muscle mass, and H2S levels, while combined therapy completely recovered. Conclusions: The combination therapy with H2S donor and PDE5i had positive effects on erectile responses through the improvement of ischemia-induced morphological and functional penile alterations in obstruction. H2S and NO may likely play a synergistic role in the regulation of erectile function and have constructive effects on clinical outcomes in male patients with ED and benign prostatic hyperplasia/lower urinary tract symptoms

Comparison of the treatment efficacies of paroxetine, fluoxetine and dapoxetine in low socioeconomic status patients with lifelong premature ejaculation

Introduction To assess the treatment efficacies of paroxetine, fluoxetine and dapoxetine in patients with lifelong premature ejaculation (PE). Material and methods One hundred and seventy male patients with lifelong PE were included in our study. Premature ejaculation profile (PEP) and Intravaginal ejaculation latency times (IELT) were recorded. Paroxetine 20 mg/d was given in Group 1 (n = 64), fluoxetine 20 mg/d was given in Group 2 (n = 47) and dapoxetine 30 mg on demand (at least two times/week) was given in Group 3 (n = 59) patients. After 1 month of treatment, the patients' IELT, PEP and patient reported clinical global impression of change (CGIC) were completed. Results The mean age was 36 +/- 9.2 years. There was no difference between the groups' age, PEP and IELT before treatment (p >0.05). PEP and IELT improved in all three groups (p <0.001). The changes in the 1st and 3rd questions of PEP was significantly higher in group 1 than in the other groups (pPEP-1 = 0.042, pPEP-3 = 0.001). The changes in the 2nd and 4th questions of PEP were similar between groups (pPEP-2 = 0.444, pPEP-4 = 0.442). In group 1 and 3 IELT changes were better than group 2 (pIIEL1-3 = 0.297, pIIEL1-2 = 0.017, pIIEL2-3 = 0.100). There was no difference between CGIC scores (p = 0.087). The treatment was terminated by 8 patients in Group 1 and 9 patients in Group 2 because of side effects. Conclusions While paroxetine treatment seemed to be better than the other medications, dapoxetine 30 mg treatment has less side effects than the two others and its' on demand usage makes it more prominent than the others

Update on Drug Interactions With Phosphodiesterase-5 Inhibitors Prescribed as First-Line Therapy for Patients with Erectile Dysfunction or Pulmonary Hypertension

Phosphodiesterase-5 inhibitors (PDE5i, sildenafil, vardenafil, tadalafil and avanafil) are a first-line medical therapy for erectile dysfunction (ED). In all likelihood, PDE5i usage will increase because sildenafil (Viagra(R) and Revatio(R)) and tadalafil (Cialis(R) and Adcirca(R)) have recently been recommended as first-line therapy for patients with pulmonary hypertension (PH). PDE5i exhibit higher plasma concentrations when co-administered with cytochrome P (CYP) 3A inhibitors, which influences their side-effect profile. The higher PDE5i plasma concentrations, caused by CYP3A inhibitors, influence the severity and timing of PDE5i drug interactions and require dose adjustment. PDE5i are safe when used with most antihypertensive agents, but co-administration with nitrates or alpha-blockers can cause severe hypotension and syncope. Dose adjustment is also necessary when PDE5i are co-administered with CYP3A inducers. The combination of oral tadalafil and bosentan (endothelin receptor antagonist) reduces tadalafil levels and requires dose adjustment. Current literature reports a number of interactions between PDE5i and other agents and further studies are needed to expand our knowledge base of these interactions. This review discusses relevant PDE5i drug interactions, including those with CYP 450 inhibitors and inducers which are frequently used during the treatment of ED and PH