Surgical Outcomes and Predictive Factors in Patients With Detrusor Underactivity Undergoing Bladder Outlet Obstruction Surgery.

PURPOSE: This study was conducted to evaluate the efficacy of bladder outlet surgery in patients with detrusor underactivity (DU) and to identify factors associated with successful outcomes. METHODS: We conducted a retrospective review of men diagnosed with DU in urodynamic studies who underwent bladder outlet surgery for lower urinary tract symptoms between May 2018 and April 2023. The International Prostate Symptom Score (IPSS) questionnaire, uroflowmetry (UFM), and multichannel urodynamic studies were administered. Successful treatment outcomes were defined as either an IPSS improvement of at least 50% or the regaining of spontaneous voiding in patients urethral catheterization prior to surgery. RESULTS: The study included 93 male patients. Men diagnosed with significant or equivocal bladder outlet obstruction (BOO) experienced significant postoperative improvements in IPSS (from 20.6 to 6.0 and from 17.4 to 6.5, respectively), maximum urine flow rate (from 5.0 mL/sec to 14.4 mL/sec and from 8.8 mL/sec to 12.2 mL/sec, respectively) and voiding efficiency (from 48.8% to 86.0% and from 61.2% to 85.1%, respectively). However, in the group without obstruction, the improvements in IPSS and UFM results were not significant. The presence of detrusor overactivity (odds ratio [OR], 3.152; P=0.025) and preoperative urinary catheterization (OR, 2.756; P=0.040) were associated with favorable treatment outcomes. Conversely, an unobstructed bladder outlet was identified as a negative prognostic factor. CONCLUSION: In men with DU accompanied by equivocal or significant BOO, surgical intervention to alleviate the obstruction may enhance the IPSS, quality of life, and UFM results. However, those with DU and an unobstructed bladder outlet face a comparatively high risk of treatment failure. Preoperative detrusor overactivity and urinary catheterization are associated with more favorable surgical outcomes. Consequently, active deobstructive surgery should be considered for patients with DU who are experiencing urinary retention.

Therapeutic efficacy of 180-W GreenLight laser photoselective vaporization of the prostate for storage symptoms concomitant with benign prostatic obstruction and a search for outcome predictors.

PURPOSE: Benign prostatic obstruction (BPO) is the most common cause of lower urinary tract symptoms among men. GreenLight photoselective vaporization of the prostate (GL-PVP) using a 180-W Xcelerated performance system (XPS) laser is a well-established method for treating BPO-induced voiding symptoms. However, its therapeutic effects on storage symptoms remain unclear. This study aimed to analyze the storage outcomes in patients who underwent 180-W XPS GL-PVP for BPO and to identify outcome predictors. MATERIALS AND METHODS: Patients who underwent 180-W XPS GL-PVP for BPO between May 2018 and May 2021 were retrospectively reviewed. Data on clinical characteristics, prostate volume, preoperative and postoperative International Prostate Symptom Scores (IPSS), and preoperative urodynamic parameters were collected. A favorable storage outcome was defined as ≥50% reduction in the IPSS storage subscore. RESULTS: Ninety-nine male patients were included, with a mean age of 69.4 ± 9.6 years and a baseline prostatic volume of 75.9 ± 33.1 mL. The IPSS total, storage, and voiding subscores significantly decreased after GL-PVP (all p < 0.001). Seventy-two patients achieved favorable storage outcome at 6 months. Multivariate analysis revealed that detrusor underactivity was predictive of unfavorable storage outcomes (p = 0.022), while IPSS voiding-to-storage subscore ratio >1.25 and the presence of detrusor overactivity were predictive of favorable storage outcomes (p = 0.008 and 0.033, respectively). CONCLUSION: 180-W XPS GL-PVP provided excellent outcomes in both voiding and storage lower urinary tract symptoms concomitant with BPO. Preoperative IPSS and multichannel urodynamic parameters including detrusor overactivity and underactivity are valuable predictors of postoperative storage outcomes.

Risk of secondary primary malignancies in survivors of upper tract urothelial carcinoma: A nationwide population-based analysis.

BACKGROUND: To investigate the cancer types and risk factors of secondary primary malignancy (SPM) in patients with upper tract urothelial carcinoma (UTUC) in Taiwan. METHODS: Using National Health Insurance Research Dataset and catastrophic illness registry, we enrolled newly diagnosed UTUC patients from 2000 to 2013. Those without catastrophic illness registration were excluded from the study. The cancer types and hazard ratios (HRs) of subsequent SPMs were calculated according to the antecedent malignancy. We analyzed the risk factors for developing SPMs using multivariate Cox proportional hazard models. RESULTS: A total of 9050 UTUC patients were registered and 2187 (24.2%) patients developed SPMs during the study period. As compared with primary UTUC, the relative risk ratios of SPM was 2.5 folds and 18% higher in those with antecedent non-UC malignancy and with bladder cancer history, respectively. Totally, 387 (37.8%) of 1022 UTUC patients with antecedent non-UC malignancy developed subsequent SPM after UTUC diagnosis. The antecedent and subsequent cancer types are similar and kidney cancer is most common, followed by hepatoma. Multivariate analysis showed that a history of antecedent non-UC malignancy is the most unfavorable factor for SPM development (HR, 2.50; 95% CI, 2.23-2.81), followed by liver disease, male gender, antecedent bladder cancer history, age ≥ 75 years, and chronic kidney disease. CONCLUSIONS: Our study, conducted in Taiwan and involving 9050 UTUC patients, meticulously examined the types of SPM and the associated risk factors. Our research unearthed several pivotal discoveries: a preceding history of non-UC malignancies emerged as the single most influential factor contributing to the occurrence of subsequent cancers, followed by liver disease, male gender, antecedent bladder cancer history, age ≥75 years, and chronic kidney disease. Futhermore, kidney cancer emerged as the predominant subsequent malignancy, closely trailed by hepatoma..

The influence of sex difference on behavior and adult hippocampal neurogenesis in C57BL/6 mice.

Animal models have been used extensively in in vivo studies, especially within the biomedical field. Traditionally, single-sex studies, mostly males, are used to avoid any potential confounding variation caused by sex difference and the female estrous cycle. Historically, female animal subjects are believed to exhibit higher variability, and this could increase the statistical power needed to test a hypothesis. This study sets out to evaluate whether a sex difference does exist in mouse behavior, and whether female mice featured higher variability. We assessed the sensorimotor skills, anxiety-like behavior, depression-like behavior, and cognitive abilities of mice through a series of commonly used behavioral tests. Except for the stronger grip force and lower tactile sensory sensitivity detected in male mice, there was no significant difference between males and females in other tests. Furthermore, immunolabeling of neurogenesis markers suggested no significant difference between sexes in adult hippocampal neurogenesis. Within group variances were equivalent; females did not exhibit higher variability than males. However, the overall negative results could be due to the limitation of small sample size. In conclusion, our study provides evidence that sex difference in mice does not significantly influence these commonly used behavioral tests nor adult neurogenesis under basal conditions. We suggest that female mice could also be considered for test inclusion in future experiment design.

Radial stem astrocytes (aka neural stem cells): Identity, development, physio-pathology, and therapeutic potential.

Adult neurogenesis is a striking example of neuroplasticity, which enables adaptive network remodelling in response to all forms of environmental stimulation in physiological and pathological contexts. Dysregulation or cessation of adult neurogenesis contributes to neuropathology negatively affecting brain functions and hampering regeneration of the nervous tissue while targeting adult neurogenesis may provide the basis for potential therapeutic interventions. Neural stem cells in the adult mammalian brain are at the core and the entry point of adult neurogenesis. By their origin and properties, these cells belong to astroglia, and are represented by stem radial astrocytes (RSA) which exhibit multipotent "stemness". In the neurogenic niches, RSA interact with other cellular components, including protoplasmic astrocytes, which in turn regulate their neurogenic activity. In pathology, RSA become reactive, which affects their neurogenic capabilities, whereas reactive parenchymal astrocytes up-regulate stem cell hallmarks and are able to generate progeny that remain within astrocyte lineage. What makes RSA special is their multipotency, represented by self-renewing capacity capability to generate other cellular types as progeny. A broad understanding of the cellular features of RSA and parenchymal astrocytes provides an insight into the machinery that promotes/suppresses adult neurogenesis, clarifying principles of network remodelling. In this review, we discuss the cellular hallmarks, research tools, and models of RSA and astrocytes of the subventricular zone along the lateral ventricle and dentate gyrus of the hippocampus. We also discuss RSA in ageing, which has a great impact on the proliferative capacity of RSA, as well as the potential of RSA and astrocytes in therapeutic strategies aimed at cell replacement and regeneration.

Intravesical Injection of Botulinum Toxin Type A in Patients with Refractory Overactive Bladder-Results between Young and Elderly Populations, and Factors Associated with Unfavorable Outcomes.

Intravesical botulinum toxin type A (BoNT-A) injection has been recognized as the standard treatment for refractory overactive bladder (OAB). However, its therapeutic efficacy and safety have not been thoroughly reviewed in elderly patients. This study aims to provide treatment outcomes for patients aged ≥75 years, and to identify factors associated with unfavorable outcomes. Patients receiving intradetrusor injections of 100 U onabotulinumtoxinA for refractory OAB between 2011 and 2021 were retrospectively reviewed. Urodynamic parameters, underlying comorbidities, subjective success, and unfavorable outcomes were assessed. A total of 192 patients were included, and 65 of them were classified into the elderly group. For the elderly group, 60.0% experienced subjective dryness, and 84.6% remained subjective success at 6 months after the injections. The prevalence rates of common unfavorable outcomes, including urinary tract infections, large post-void residual urine volume, and urinary retention, were 9.2%, 27.7%, and 12.3%, respectively. Multivariate analysis revealed that female, baseline urodynamic parameters, and diabetes mellitus were associated with unfavorable outcomes in the elderly group. Intravesical BoNT-A injections provide comparable therapeutic efficacy and safety concerns in elderly patients with refractory OAB. A thorough consultation for treatment benefits and possible adverse events is mandatory before the procedure.

The Systemic Immune-Inflammation Index (SII) Increases the Prognostic Significance of Lymphovascular Invasion in Upper Tract Urothelial Carcinoma After Radical Nephroureterectomy.

Purpose: Lymphovascular invasion (LVI) and systemic immune-inflammation index (SII) both have been proved to correlate with oncologic outcomes in upper tract urothelial carcinoma (UTUC). We hypothesize that integrating SII with LVI may be an aid for risk-stratification of prognosis. This study aimed to evaluate the prognostic significance of combined SII and LVI in patients with localized UTUC. Patients and Methods: A retrospective analysis of clinicopathological data of 554 UTUC patients who underwent radical nephroureterectomy (RNU) was conducted. The SII was calculated using the equation (preoperative serum neutrophil*platelet/lymphocyte). Use of Kaplan-Meier analyses and Cox proportional hazards models were to evaluate associations of combining SII and LVI with overall survival (OS), cancer-specific survival (CSS), and progression-free survival (PFS). Furthermore, receiver operating characteristic (ROC) analysis was applied to estimate predictive ability of combining SII and LVI for oncological outcomes. Results: Positive LVI was significantly associated with advanced stage, high grade, necrosis, lymph node metastasis, and high-level SII. Positive LVI and high-level SII co-existence was significantly associated with unfavorable OS, CSS, and PFS in Kaplan-Meier analyses (all p < 0.001) and was an independent indicator of OS, CSS, and PFS (HR [95% CI]: 3.918 [2.168-7.078], 5.623 [2.679-11.801], 3.377 [2.138-5.334]), respectively) in multivariate analyses. Furthermore, adding LVI and SII to a model that included standard pathologic predictors exhibited a better ability to predict survival in ROC analysis. Conclusion: The integration of SII and LVI was demonstrated to be a potential factor of poor outcomes in patients with localized UTUC. Notably, the combined use of LVI and SII can be a feasible and complementary factor to TNM staging in the prognostic assessment of UTUC patients in clinical practice. The validity of combination of the two markers would be considered in future prospective studies to evaluate its usefulness in staging and application of post-operative chemo or immunotherapy.

Pre­existing renal insufficiency synchronous with high preoperative neutrophil­to­lymphocyte ratio as a risk factor of intravesical recurrence in patients with pure upper tract urothelial carcinoma after radical nephroureterectomy.

The present study aimed to evaluate the influence of pre-treatment neutrophil-to-lymphocyte ratio (NLR) on bladder recurrence in patients with impaired renal function following radical nephrouretectomy (RNU) to treat pure upper tract urothelial carcinoma (UTUC). Retrospective data of 362 patients with pure UTUC who underwent RNU between 2008 and 2019 were analyzed. Kaplan-Meier analyses were performed to evaluate the association of preoperative NLR and estimation of the glomerular filtration rate (eGFR) with intravesical recurrence-free survival (IVRF). Furthermore, multivariate analyses were conducted to determine independent factors for predicting IVRF. In the retrospective cohort study of 362 patients, 103 patients (28%) had intravesical recurrence in a median follow-up of 50.1 months; among those, 85 (83%) developed bladder recurrence within two years after RNU. The Kaplan-Meier analysis indicated that patients exhibiting lower eGFR and higher NLR showed significantly poor IVRF rates (P=0.044). The simultaneous presence of eGFR <45 and NLR >3.8 was an independent factor for the shorter IVRF time in multivariate analysis with Cox's proportional hazards model. Most intravesical recurrences occurred within two years after RNU, particularly in pre-existing poor eGFR patients with preoperative high NLR. Moreover, pre-existing moderate to severe CKD synchronous with pre-operative NLR >3.8 was demonstrated as an independent factor for subsequent bladder recurrence in patients with pure UTUC following RNU. Therefore, such high-risk patients ought to be provided with close bladder monitoring during the follow-up.

The Use of Propofol versus Dexmedetomidine for Patients Receiving Drug-Induced Sleep Endoscopy: A Meta-Analysis of Randomized Controlled Trials.

The sedation outcomes associated with dexmedetomidine compared with those of propofol during drug-induced sleep endoscopy (DISE) remains unclear. Electronic databases (i.e., the Cochrane controlled trials register, Embase, Medline, and Scopus) were searched from inception to 25 December 2020 for randomized controlled trials (RCTs) that evaluated the sedation outcomes with dexmedetomidine or propofol in adult patients diagnosed with obstructive sleep apnea (OSA) receiving DISE. The primary outcome was the difference in minimum oxygen saturation (mSaO2). Five RCTs (270 participants) published between 2015 and 2020 were included for analysis. Compared with dexmedetomidine, propofol was associated with lower levels of mSaO2 (mean difference (MD) = -7.24, 95% confidence interval (CI) -12.04 to -2.44; 230 participants) and satisfaction among endoscopic performers (standardized MD = -2.43, 95% CI -3.61 to -1.26; 128 participants) as well as a higher risk of hypoxemia (relative ratios = 1.82, 95% CI 1.2 to 2.76; 82 participants). However, propofol provided a shorter time to fall asleep and a lower risk of failed sedation compared with dexmedetomidine. No significant difference was found in other outcomes. Compared with propofol, dexmedetomidine exhibited fewer adverse effects on respiratory function and provided a higher level of satisfaction among endoscopic performers but was associated with an elevated risk of failed sedation.

The effect of nerve growth factor on supporting spatial memory depends upon hippocampal cholinergic innervation.

Nerve growth factor (NGF) gene therapy has been used in clinical trials of Alzheimer's disease. Understanding the underlying mechanisms of how NGF influences memory may help develop new strategies for treatment. Both NGF and the cholinergic system play important roles in learning and memory. NGF is essential for maintaining cholinergic innervation of the hippocampus, but it is unclear whether the supportive effect of NGF on learning and memory is specifically dependent upon intact hippocampal cholinergic innervation. Here we characterize the behavior and hippocampal measurements of volume, neurogenesis, long-term potentiation, and cholinergic innervation, in brain-specific Ngf-deficient mice. Our results show that knockout mice exhibit increased anxiety, impaired spatial learning and memory, decreased adult hippocampal volume, neurogenesis, short-term potentiation, and cholinergic innervation. Overexpression of Ngf in the hippocampus of Ngf gene knockout mice rescued spatial memory and partially restored cholinergic innervations, but not anxiety. Selective depletion of hippocampal cholinergic innervation resulted in impaired spatial memory. However, Ngf overexpression in the hippocampus failed to rescue spatial memory in mice with hippocampal-selective cholinergic fiber depletion. In conclusion, we demonstrate the impact of Ngf deficiency in the brain and provide evidence that the effect of NGF on spatial memory is reliant on intact cholinergic innervations in the hippocampus. These results suggest that adequate cholinergic targeting may be a critical requirement for successful use of NGF gene therapy of Alzheimer's disease.

The Crosstalk of Long Non-Coding RNA and MicroRNA in Castration-Resistant and Neuroendocrine Prostate Cancer: Their Interaction and Clinical Importance.

Prostate cancer is featured by its heterogeneous nature, which indicates a different prognosis. Castration-resistant prostate cancer (CRPC) is a hallmark of the treatment-refractory stage, and the median survival of patients is only within two years. Neuroendocrine prostate cancer (NEPC) is an aggressive variant that arises from de novo presentation of small cell carcinoma or treatment-related transformation with a median survival of 1-2 years from the time of diagnosis. The epigenetic regulators, such as long non-coding RNAs (lncRNAs) and microRNAs (miRNAs), have been proven involved in multiple pathologic mechanisms of CRPC and NEPC. LncRNAs can act as competing endogenous RNAs to sponge miRNAs that would inhibit the expression of their targets. After that, miRNAs interact with the 3' untranslated region (UTR) of target mRNAs to repress the step of translation. These interactions may modulate gene expression and influence cancer development and progression. Otherwise, epigenetic regulators and genetic mutation also promote neuroendocrine differentiation and cancer stem-like cell formation. This step may induce neuroendocrine prostate cancer development. This review aims to provide an integrated, synthesized overview under current evidence to elucidate the crosstalk of lncRNAs with miRNAs and their influence on castration resistance or neuroendocrine differentiation of prostate cancer. Notably, we also discuss the mechanisms of lncRNA-miRNA interaction in androgen receptor-independent prostate cancer, such as growth factors, oncogenic signaling pathways, cell cycle dysregulation, and cytokines or other transmembrane proteins. Conclusively, we underscore the potential of these communications as potential therapeutic targets in the future.

Clinical Practice Guideline for Tripterygium Glycosides/Tripterygium wilfordii Tablets in the Treatment of Rheumatoid Arthritis.

Tripterygium wilfordii Hook F (TwHF) is one of the most commonly used and effective traditional Chinese herbal medicines against rheumatoid arthritis (RA). Both Tripterygium Glycoside Tablets (TGT) and Tripterygium wilfordii Tablets (TWT) are the representative TwHF-based agents enrolled into the 2019 edition of Medicine Catalog for National Basic Medical Insurance, Injury Insurance, and Maternity Insurance. However, individual differences in TGT/TWT response across patients usually exist in the process of treating RA, implying that the clinical application of the two agents may not be standardized leading to the ineffective treatment and the risk of side effects. Growing evidence show that the bioactive constituents of TwHF may often have toxicity, the package insert of TGT and TWT may not be described in detail, and the therapeutic windows of the two agents are narrow. Thus, it is an urgent task to develop a standardized clinical practice guideline for TGT and TWT in the treatment of RA. In the current study, a group of clinical experts of traditional Chinese medicine and Western medicine in the research field of rheumatism diseases, pharmacists, and methodologists of evidence-based medicine were invited to select the clinical questions, to determine the levels of the evidence and the strength of the recommendations, and to develop the recommendations and good practice points. The guideline is formed based on the combination of clinical research evidence and expert experience (evidence-based, consensus, supplemented by experience). The clinical problems which are supported by clinical evidence may form recommendations, and the clinical problems without clinical evidence may form experts' suggestions. Both recommendations and experts' suggestions in this guideline summarized the clinical indications, usage, dosage, combined medication, and safety of TGT and TWT against RA systematically and comprehensively, which may offer a professional guidance in the context of the clinical application of the two TwHF-based agents.

Association of Prostate Blood Flow with Male Lower Urinary Tract Symptoms.

PURPOSE: To investigate the association of prostate blood flow (PBF) with lower urinary tract symptoms (LUTS) in aged males using Doppler spectral waveform (DSW) analysis. PATIENTS AND METHODS: We performed a prospective analysis involving 133 aged males with clinical diagnosis of LUTS. DSW parameters (peak-systolic velocity (PSV), end-diastolic velocity (EDV), and resistive index (RI)) were measured at bilateral neurovascular bundles (NVB), periurethral, and capsular branches by Doppler transrectal ultrasound with the patient in the right lateral decubitus position. The associations of PBF parameters and the International Prostate Symptom Score (IPSS) were analyzed. RESULTS: Overall, total IPSS scores were significantly correlated with the RI of bilateral NVB vessels (r2 = 0.03, 0.04; p = 0.04, 0.02, respectively), and PSV of left NVB vessels. PSV of bilateral NVB vessels were associated with the storage score (p = 0.022 and p = 0.016), but not with the voiding score. The sum of the frequency and urgency score was also associated with EDV of both capsular and urethral branches (p = 0.043 and p = 0.009, respectively), and PSV of NVB vessels on both sides (p = 0.045 and p = 0.019, respectively). CONCLUSIONS: There is an association between PBF and LUTS, especially with storage symptoms. The findings may provide some insights in understanding the underlying pathophysiology of lower urinary tract dysfunction.

Abatement of sulfur hexafluoride emissions from the semiconductor manufacturing process by atmospheric-pressure plasmas.

Sulfur hexafluoride (SF6) is an important gas for plasma etching processes in the semiconductor industry. SF6 intensely absorbs infrared radiation and, consequently, aggravates global warming. This study investigates SF6 abatement by nonthermal plasma technologies under atmospheric pressure. Two kinds of nonthermal plasma processes--dielectric barrier discharge (DBD) and combined plasma catalysis (CPC)--were employed and evaluated. Experimental results indicated that as much as 91% of SF6 was removed with DBDs at 20 kV of applied voltage and 150 Hz of discharge frequency for the gas stream containing 300 ppm SF6, 12% oxygen (O2), and 40% argon (Ar), with nitrogen (N2) as the carrier gas. Four additives, including Ar, O2, ethylene (C2H4), and H2O(g), are effective in enhancing SF6 abatement in the range of conditions studied. DBD achieves a higher SF6 removal efficiency than does CPC at the same operation condition. But CPC achieves a higher electrical energy utilization compared with DBD. However, poisoning of catalysts by sulfur (S)-containing species needs further investigation. SF6 is mainly converted to SOF2, SO2F4, sulfur dioxide (SO2), oxygen difluoride (OF2), and fluoride (F2). They do not cause global warming and can be captured by either wet scrubbing or adsorption. This study indicates that DBD and CPC are feasible control technologies for reducing SF6 emissions.