Thulium fiber laser vs Ho:YAG in RIRS: a prospective randomized clinical trial assessing the efficacy of lasers and different fiber diameters (150 µm and 200 µm).

INTRODUCTION: The aims of the study: (1) to compare the Super Pulse Thulium Fiber Laser (SP TFL) and the holmium: yttrium-aluminium-garnet (Ho:YAG) lasers in retrograde intrarenal surgery (RIRS); (2) to compare the efficacy of SP TFL laser fibers of different diameters (150 µm and 200 µm). METHODS: A prospective randomized single-blinded trial was conducted. Patients with stones from 10 to 20 mm were randomly assigned RIRS in three groups: (1) SP TFL (NTO IRE-Polus, Russia) with fiber diameter of 150 µm; (2) SP TFL with 200-µm fiber; and (3) Ho:YAG (Lumenis, USA) with 200-µm fiber. RESULTS: Ninety-six patients with kidney stones were randomized to undergo RIRS with SP TFL using a 150-µm fiber (34 patients) and a 200-µm fiber (32 patients) and RIRS with Ho:YAG (30 patients). The median laser on time (LOT) in the 200-µm SP TFL group was 9.2 (6.2-14.6) min, in 150-µm SP TFL-11.4 (7.7-14.9) min (p = 0.390), in Ho:YAG-14.1 (10.8-18.1) min (p = 0.021). The total energy consumed in 200-µm SP TFL was 8.4 (5.8-15.2) kJ; 150-µm SP TFL - 10.8 (7.3-13.5) kJ (p = 0.626) and in Ho:YAG-15.2 (11.1-25.3) kJ (p = 0.005). CONCLUSIONS: Irrespective of the density, RIRS with SP TFL laser has proven to be both a safe and effective procedure. Whilst the introduction of smaller fibers may have the potential to reduce the duration of surgery, SP TFL results in a reduction in the LOT and total energy for stone ablation in RIRS compared with Ho:YAG.

A systematic review and meta-analysis of placebo effect in clinical trials on chronic prostatitis/chronic pelvic pain syndrome.

BACKGROUND: It is a common practice to control efficacy of pharmacological treatment with a placebo group. However, placebo itself may affect subjective and even objective results. The purpose of this study was to evaluate the placebo effect on symptoms of CP/CPPS to improve future clinical trials. METHODS: A search at three databases (Scopus, MEDLINE, and Web of Science) was conducted to identify double-blind placebo-controlled clinical trials on the treatment of CP/CPPS published until April 2021. The primary outcome - National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) score. SECONDARY OUTCOMES: Qmax, PVR, IPSS, and prostate volume. RESULTS: A total of 3502 studies were identified. Placebo arms of 42 articles (5512 patients, median 31 patients) were included in the systematic review. Systematic review identified positive changes in the primary endpoint, meta-analysis of 10 articles found that NIH-CPSI total score results were significantly influenced by placebo, mean difference -4.2 (95% confidence interval [CI]: -6.31, -2.09). Mean difference of NIH-CPSI pain domain was -2.31 (95% CI: -3.4, -1.21), urinary domain -1.12 (95% CI: -1.62, -0.62), quality of life domain -1.67 (95% CI: -2.38, -0.96); p < 0.001 for all. In case of the objective indicator - Qmax, there were three articles included in the meta-analysis. Qmax mean change from baseline was 0.68 (95% CI: -0.85, 2.22, p = 0.38). Systematic review showed no significant changes in pain, measured by VAS or other scores, IPSS and PVR. CONCLUSIONS: Placebo significantly affected the subjective parameters (NIH-CPSI) and limitedly affected various other measurements of pain (visual analog scale, McGill pain questionnaire). There was no long-term effect on IPSS and objective measurements (Qmax, PVR). This study can be used in further clinical trials to develop general rules of CPPS treatment assessment.

Randomized prospective trial of the severity of irritative symptoms after HoLEP vs ThuFLEP.

PURPOSE: To compare the short-term postoperative functional outcomes and severity of irritative symptoms following holmium and thulium fiber laser enucleation (HoLEP and ThuFLEP). METHODS: This prospective randomized single-blinded study was performed in accordance with CONSORT. The inclusion criteria were IPSS > 20 or Qmax < 10 ml/s. Patients were randomized between HoLEP and ThuFLEP. Demographics, objective data (PSA, prostate volume, etc.), data on urinary and sexual function (IPSS, IIEF, QoL, QUID, Qmax, ICIQ-MLUTS) were collected. Detailed perioperative information and postoperative data on functional outcomes at 1, 2, 3, 4, 6, 8, 10, 12 weeks and 6 months were collected. RESULTS: Data on 163 participants were included (77-HoLEP, 86-ThuFLEP). No differences were found in surgery duration; number of postoperative complications (Clavien-Dindo I-III), catheterization time and hospital stay. Functional outcomes up to 6 months didn't differ between the groups (IPPS, IIEF, QoL, QUID, ICIQ-MLUTS, Qmax, p > 0.05). Total ICIQ-MLUTS, bother and voiding scores at 1 and 3 months significantly increased compared with the baseline in both groups (p < 0.05). No difference between the groups were observed. In HoLEP the SUI series rate was 1.3% and 1.3% after 3 and 6 months following the procedure; in ThuFLEP: it was 3.5% and 2.3% respectively (p = 0.35 and p = 0.54). CONCLUSION: The preliminary results of the study showed no apparent differences in functional outcomes (IPSS, Qmax), rate of SUI or irritative symptoms. Both ThuFLEP and HoLEP are efficient ways of treating benign prostatic obstruction. Both surgeries are comparable in terms of duration and postoperative complication rates.

Molecular and behavioural abnormalities in the FUS-tg mice mimic frontotemporal lobar degeneration: Effects of old and new anti-inflammatory therapies.

Genetic mutations in FUS, a DNA/RNA-binding protein, are associated with inherited forms of frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS). A novel transgenic FUS[1-359]-tg mouse line recapitulates core hallmarks of human ALS in the spinal cord, including neuroinflammation and neurodegeneration, ensuing muscle atrophy and paralysis, as well as brain pathomorphological signs of FTLD. However, a question whether FUS[1-359]-tg mouse displays behavioural and brain pro-inflammatory changes characteristic for the FTLD syndrome was not addressed. Here, we studied emotional, social and cognitive behaviours, brain markers of inflammation and plasticity of pre-symptomatic FUS[1-359]-tg male mice, a potential FTLD model. These animals displayed aberrant behaviours and altered brain expression of inflammatory markers and related pathways that are reminiscent to the FTLD-like syndrome. FTLD-related behavioural and molecular Journal of Cellular and Molecular Medicine features were studied in the pre-symptomatic FUS[1-359]-tg mice that received standard or new ALS treatments, which have been reported to counteract the ALS-like syndrome in the mutants. We used anti-ALS drug riluzole (8 mg/kg/d), or anti-inflammatory drug, a selective blocker of cyclooxygenase-2 (celecoxib, 30 mg/kg/d) for 3 weeks, or a single intracerebroventricular (i.c.v.) infusion of human stem cells (Neuro-Cells, 500 000-CD34+ ), which showed anti-inflammatory properties. Signs of elevated anxiety, depressive-like behaviour, cognitive deficits and abnormal social behaviour were less marked in FUS-tg-treated animals. Applied treatments have normalized protein expression of interleukin-1ß (IL-1ß) in the prefrontal cortex and the hippocampus, and of Iba-1 and GSK-3ß in the hippocampus. Thus, the pre-symptomatic FUS[1-359]-tg mice demonstrate FTLD-like abnormalities that are attenuated by standard and new ALS treatments, including Neuro-Cell preparation.

A Review of How Lasers Are Used in UTUC Surgery: Can the Choice of Laser Affect Outcomes?

Upper tract urothelial carcinoma (UTUC) is a relatively rare disease with an aggressive phenotype compared to urothelial carcinoma in the bladder. In recent years, kidney-sparing surgery (KSS) and, in particular, endoscopic surgery have become the procedure of choice among urologists where the treatment of localized UTUC is concerned. Endoscopy tends to result in satisfactory oncological disease control while lowering morbidity and minimizing complications amongst the appropriately selected cohort of patients. While endoscopic surgery for UTUC might appear to be standardized, it, in fact, differs considerably depending on the source of energy used for resection/ablation. There has been little reliable data up to now on which laser energy source is the most superior. The goal of this review is, therefore, to outline the results of endoscopic UTUC treatment using different lasers and to analyze how these laser-tissue interactions may affect the surgery. We start by pointing out that the data remains insufficient when trying to determine which laser is the most effective in the endoscopic management of UTUC. The ever-growing number of indications for minimally invasive treatment and the increasing number of centers using laser surgery will, hopefully, lead to novel randomized controlled trials that compare the performance characteristics of the lasers as well as the effects of UTUC on patients.

A Systematic Review of Circulating Tumor Cells Clinical Application in Prostate Cancer Diagnosis.

The purpose of the review is to summarize the recent data on circulating tumor cells (CTC) use in clinical practice. We performed a systematic literature search using two databases (Medline and Scopus) over the past five years and the following terms: (CTC OR "circulating tumor cells" OR "liquid biopsy") AND prostate. The primary outcome was CTC predictive value for prostate cancer (PC) progression and survival. The secondary outcomes were the CTC predictive value for therapy response and the results of CTC detection depending on the assessment method. In metastatic PC, the CTC count showed itself to be a prognostic marker in terms of clinically important features, namely survival rates and response to treatment. CTC concentration was significantly associated with the overall survival and progression-free survival rates. A strong association between the overall survival or progression-free survival rate and CTC concentration could be observed. Variant-7 androgen receptors-positive (AR-V7-positive) patients showed a poor response to androgen receptor signaling (ARS) inhibitors, but this did not compromise their response to taxanes. In localized PC, only positive Cluster of Differentiantion 82 protein (CD82+) correlated with a higher survival rate. CTC count and AR-V7 expression showed itself to be a valuable biomarker for survival in metastatic PC and response to ARS-inhibitors. CTC diagnostic performance for localized PC or for screening and early detection is not high enough to show additional value over the other biomarkers.

Thulium Fiber Laser Enucleation of the Prostate: Prospective Study of Mid- and Long-Term Outcomes in 1328 Patients.

Objective: The objective of our study was to estimate the long-term efficacy and safety of thulium fiber laser enucleation of the prostate (ThuFLEP). Materials and Methods: We analyzed patients who underwent ThuFLEP due to lower urinary tract symptoms (LUTS) related to benign prostatic obstruction (BPO). Both the pre- and perioperative data as well as the follow-up data for 3 years were evaluated: prostate volume, postvoid residual (PVR), maximum flow rate (Qmax), International Prostate Symptom Score (IPSS), quality of life (QoL), prostate-specific antigen level, and the complication rate. Intraoperative data relating to the weight of resected tissue, the duration of surgery, catheterization, and data on hospital stays were also collected. A subgroup analysis was performed to assess whether older patients (>65 years) or those with larger glands (>80 cc) are prone to increased complication risks. Results: A total of 1328 patients were included in the analysis. The mean age was 66.9 ± 7.5 years. Mean prostate volume was 86.9 ± 41.9 (20-330) cc. All the functional parameters (IPSS, QoL, PVR, Qmax) significantly improved after surgery (p < 0.05) and showed durable improvement up to 3 years of follow-up. The frequency of late complications was as follows: stress urinary incontinence-1.2%; urethral stricture-1.1%; and bladder neck contracture-0.9%. Subgroup analyses revealed increased urinary tract infection frequency in older patients (3.5% vs 0.8%, p = 0.003) as well as higher rate of stress urinary incontinence (0.4% vs 1.8%, p = 0.002) and higher rate of clot retention (11.3% vs 4.4%, p < 0.001) in those with larger glands. Conclusions: Irrespective of the patient's age and prostate volume, ThuFLEP represents an effective and durable technique of endoscopic enucleation characterized by a low incidence of complications after 3 years of follow-up. In the hands of an experienced surgeon, ThuFLEP can rightly be a promising alternative to holmium laser enucleation of the prostate for treatment of LUTS associated with BPO.

Systematic Review: The Learning Curve for Robot-Assisted Radical Cystectomy-What Do We Know?

Background: The aim of this systematic review is to assess the robot-assisted radical cystectomy (RARC) learning curve (LC), which is important to consider in both risk-benefit assessment and training. Materials and Methods: We performed a systematic literature search using two databases (Medline and Scopus) with the search query "learning AND cystectomy" and included all articles containing data on the assessment of the RARC LC. Our primary outcome was the surgeons' experience (a number of performed procedures) required to achieve the LC plateau. The secondary outcomes related to the methods for assessing the relevant LC. Results: Between 9 and 50 procedures were required to reduce the operation time significantly. The data on estimated blood loss during RARC are somewhat controversial. To optimize the lymph node (LN) yield, it was necessary to treat between 20 and 50 patients. The LC for positive surgical margin was described only in one study, it was completed after 24-30 cases. Between 10 and 15 cases were necessary to reduce length of stay (LOS). Complications became less frequent after 10 to 75 patients but there was no clear plateau in the figures. Conclusions: Based on the relevant assessment criteria, the RARC LC length varies from 10 to 50 cases. The most common criteria for evaluating the learning experience include operation time and the LN yield. Blood loss, length of stay, and complications rate show variable outcomes and may be harder to use systematically as a means of LC assessment.

Thiamine and benfotiamine counteract ultrasound-induced aggression, normalize AMPA receptor expression and plasticity markers, and reduce oxidative stress in mice.

The negative societal impacts associated with the increasing prevalence of violence and aggression is increasing, and, with this rise, is the need to understand the molecular and cellular changes that underpin ultrasound-induced aggressive behavior. In mice, stress-induced aggression is known to alter AMPA receptor subunit expression, plasticity markers, and oxidative stress within the brain. Here, we induced aggression in BALB/c mice using chronic ultrasound exposure and examined the impact of the psychoactive anti-oxidant compounds thiamine (vitamin B1), and its derivative benfotiamine, on AMPA receptor subunit expression, established plasticity markers, and oxidative stress. The administration of thiamine or benfotiamine (200 mg/kg/day) in drinking water decreased aggressive behavior following 3-weeks of ultrasound exposure and benfotiamine, reduced floating behavior in the swim test. The vehicle-treated ultrasound-exposed mice exhibited increases in protein carbonyl and total glutathione, altered AMPA receptor subunits expression, and decreased expression of plasticity markers. These ultrasound-induced effects were ameliorated by thiamine and benfotiamine treatment; in particular both antioxidants were able to reverse ultrasound-induced changes in GluA1 and GluA2 subunit expression, and, within the prefrontal cortex, significantly reversed the changes in protein carbonyl and polysialylated form of neural cell adhesion molecule (PSA-NCAM) expression levels. Benfotiamine was usually more efficacious than thiamine. Thus, the thiamine compounds were able to counteract ultrasound-induced aggression, which was accompanied by the normalization of markers that have been showed to be associated with ultrasound-induced aggression. These commonly used, orally-active compounds may have considerable potential for use in the control of aggression within the community. This article is part of the Special Issue entitled 'Current status of the neurobiology of aggression and impulsivity'.