Dementia-friendly community indicators from the perspectives of people living with dementia and dementia-family caregivers.

AIMS: To identify dementia-friendly communities' indicators and their current conditions in Taiwan from the perspectives of people with dementia and dementia-family caregivers. DESIGN: This qualitative study explored the opinions and experiences of people with dementia and dementia-family caregivers regarding dementia-friendly communities. METHODS: Participants (16 people with dementia and 20 family caregivers) were recruited from neurological clinics, day care centres for people with dementia and support groups for family caregivers in the Taipei community from July - October, 2016. Data were collected in face-to-face interviews, which were tape recorded and transcribed verbatim. Transcripts were analysed by Miles and Huberman's (1994) guidelines. RESULTS: Similar indicators for dementia-friendly communities were identified in Taiwan as in other countries, including dementia-friendly care services, dementia-friendly hospitals, dementia-friendly community environment, dementia-friendly transportation, dementia-friendly stores and shops, dementia friendly people, integrated dementia-related information and community contribution- and -involvement opportunities for people with dementia. However, Taiwanese people with dementia and family caregivers described no emphasis on the potential of people with dementia to contribute to developing dementia-friendly communities and more top-down expectations for the government's role. CONCLUSION: These indicators can be a guide for developing and evaluating dementia-friendly communities in Taiwan. Differences between Taiwan and Western developed countries in indicators for dementia-friendly communities can be further explored. Community nursing assessment, interventions, and evaluation based on these dementia-friendly communities indicators can be further developed. IMPACT: This study developed indicators for dementia-friendly communities in an Asian country. These indicators can be used as a guide for developing and evaluating dementia-friendly communities.

Capillarisin blocks prostate-specific antigen expression on activation of androgen receptor in prostate carcinoma cells.

BACKGROUND: Capillarisin (Cap), an active ingredient of Artemisia capillaris extracts, has known for its anti-inflammatory, antioxidant, and anticancer properties. Functions of Cap in prostate cancer are not clear. We investigate effects of Cap on downregulation of prostate specific antigen (PSA) via modulation of androgen receptor (AR) in prostate carcinoma cells. METHODS: Cell proliferation was measured by water-soluble tetrazolium-1 (WST-1) cell proliferation assays. The PSA and AR expressions were assessed by immunoblotting and RT-qPCR assays. Effects of Cap on PSA expressions were determined by ELISA, immunoblotting, and reporter assays. Co-immunoprecipitation and immunoblotting assays were used to define the effects of Cap on dissociation of AR-heat shock protein 90 (Hsp90) interaction. RESULTS: Cap inhibited LNCaP cell growth in a dose- and/or time-dependent way without inducing poly ADP-Ribose Polymerase (PARP) cleavage. Cap not only effectively suppressed AR and PSA protein expressions, but also attenuated activations of synthetic androgen (R1881) on PSA promoter activity dose- and time-dependently. The Cap pretreatment abrogated effects of R1881 on AR activity by reducing AR translocation to the nucleus. Immunoblotting assays indicated that Cap promoted a degradation of AR proteins dose-dependently in either cycloheximide pretreated-LNCaP cells or AR-ectopic expressed PC-3 cells. Pretreatment of MG132, a proteasome inhibitor, attenuated effect of Cap on AR degradation. Cap lessened AR stability by dissociation of AR-Hsp90 interaction. CONCLUSIONS: Our results indicated that Cap inhibited growth of LNCaP cells. Cap effectively suppressed androgen activation on AR-mediated transactivation, which is AR-dependent through AR degradation and dissociation of AR-Hsp90 in prostate carcinoma cells.

Transurethral resection of the prostate achieves favorable outcomes in stroke patients with symptomatic benign prostate hyperplasia.

OBJECTIVES: To evaluate the surgical outcomes of stroke patients with symptomatic benign prostatic hyperplasia (BPH) who underwent transurethral resection of the prostate (TURP) and compare the clinical outcomes between patients with stroke and those without stroke receiving this procedure. METHODS: This retrospective cohort study analyzed claims data collected during the period of 1997-2012 from Taiwan National Health Insurance Research Database. We enrolled 6625 patients who had persistent lower urinary tract symptoms and underwent TURP for BPH. They were categorized into a stroke (n = 577) and nonstroke (n = 6048) group. Patient characteristics, postoperative clinical outcomes, medication records, and medical expenses were compared. RESULTS: Compared with the stroke group patients, those in the nonstroke group were younger, had fewer comorbidities, and more favorable postoperative clinical outcomes. Nevertheless, TURP achieved favorable outcomes in stroke patients with symptomatic BPH. In the stroke group, the rate of urinary tract infection (UTI) decreased from 34.7% during 1 year preoperatively to 29.8% during 1 year postoperatively (p = .05). The rate of urinary retention (UR) also decreased from 55.5% during 1 year preoperatively to 22.5% during 1 year postoperatively (p = .05). TURP reduced the overall medical expenses of patients with stroke. Annual patient medical expense during 1 year preoperatively, 1 year postoperatively, 2 years postoperatively, and 3 years postoperatively was NT$659,000, NT$646,000, NT$560,000, and NT$599,000, respectively. CONCLUSIONS: In patients with stroke, TURP reduces the risks of UTI and UR and annual total medical expense.

Transurethral resection of the prostate provides more favorable clinical outcomes compared with conservative medical treatment in patients with urinary retention caused by benign prostatic obstruction.

BACKGROUND: To evaluate the long-term surgical outcomes of patients with urinary retention (UR) caused by a benign prostatic obstruction (BPO) who underwent transurethral resection of the prostate (TURP), and compare their outcomes with those of patients who received medication without surgical intervention. METHODS: This retrospective cohort study analyzed claims data collected during the period of 1997-2012 from Taiwan's National Health Insurance Research Database. We examined geriatric adverse events among patients who had received a diagnosis of symptomatic benign prostatic hyperplasia and whom experienced UR, and compared those who received TURP and medication only. Primary outcomes included urinary tract infection (UTI), UR, inguinal hernia, hemorrhoids, stroke, acute myocardial infarction, and bony fracture. We excluded patients who had concomitant prostate cancer, bladder cancer, or a long-term urinary catheter indwelling, as well as those who did not receive α-blocker medication regularly. Those aged <50 or >90 years were also excluded. The enrolled patients were categorized into TURP (n = 1218) and medication only (n = 795) groups. After 1:1 propensity score matching, we recorded and compared patients' characteristics, postoperative clinical outcomes, and geriatric adverse events. RESULTS: The TURP cohort had a lower incidence of UTI and UR during the postoperative follow-up period from 2 months to 3 years than did the medication only group (20.7% vs. 28.9% and 12.5% vs. 27.6%, respectively, p < 0.001). The life-long bone fracture incidence was also lower in the TURP cohort (7.9% vs. 9.2%, p = 0.048). The incidence of other outcomes during the postoperative follow-up period did not differ between the two groups. CONCLUSIONS: Compared with conservative treatment, TURP provides more favorable clinical outcomes in patients with UR caused by BPO. Patients who underwent TURP had a lower risk of UTI, repeat UR episodes, and emergent bony fracture. Thus, early surgical intervention should be considered for such patients.

Utilization of Chinese medicine for respiratory discomforts by patients with a medical history of tuberculosis in Taiwan.

BACKGROUND: Tuberculosis (TB) is one of the world's major communicable infectious diseases, and it still imposes a great health burden in developing countries. The development of drug-resistant TB during the treatment increases the treatment complexity, and the long-term pulmonary complications after completing treatment raise the epidemic health burden. This study intended to investigate the utilization of Chinese medicine (CM) for respiratory symptoms by patients with a medical history of TB in Taiwan. METHODS: We analyzed a cohort of one million individuals who were randomly selected from the National Health Insurance Research Database in Taiwan. The inclusion criteria of patients (n = 7905) with history of TB (ICD-9-CM codes 010-018 and A02) were: (1) TB diagnosed between January 1, 1997 and December 31, 2010 (2) 18 years old or over (3) Clinical records for at least 2 months with complete demographic information (4) Record of treatment with first-line TB medication prescriptions. CM users for conditions other than respiratory discomforts (n = 3980) were excluded. Finally, a total of 3925 TB patients were categorized as: CM users for respiratory discomforts (n = 2051) and non-CM users (n = 1874). RESULTS: Among the 3925 subjects, 2051 (52.25%) were CM users, and 1874 (44.753%) were non-CM users. Female patients and those who were younger (18-39 y/o) and who lived in urbanized areas relatively tended to be CM users (p < .0001). Most of the CM users (1944, 94.78%) received Chinese medicines. The most commonly prescribed herbal formulas and single herbs were Xiao-Qing-Long-Tang and Radix Platycodonis (Jie-Geng), respectively. The core pattern of Chinese medicines for TB patients consisted of Ma-Xing-Gan-Shi-Tang, Bulbus Fritillariae Thunbergii (Bei-Mu), Radix Platycodonis (Jie-Geng) and Semen Armeniacae (Xing-Ren). CONCLUSIONS: The use of CM is popular among patients with a medical history of TB complicated with long-term respiratory discomforts in Taiwan. Further pharmacological investigations and clinical trials are required.

Caregiving demands, job demands, and health outcomes for employed family caregivers of older adults with dementia: Structural equation modeling.

Many family caregivers are also employed full- or part-time and are known to be affected by job demands. This study explored the mediating effect of job demands on the relationship between caregiving demands and caregiver health outcomes in primary family caregivers of older persons with dementia in Taiwan (N = 214). A cross-sectional design using a self-completed structured questionnaire was implemented. Structural equation modeling analyses showed that job demands partially mediated the relationship between caregiving demands and caregiver health outcomes. The indirect effect of caregiving demands on caregiver health outcomes through job demands was 0.208 (95% confidence interval: 0.053 - 0.335). Nurses should evaluate job demands when screening for high-risk caregiver groups vulnerable to high caregiving demand. Interventions aimed at lessening both caregiving demands and job demands may improve caregiver health outcomes for family caregivers of older adults with dementia.

Fully human chitinase-3 like-1 monoclonal antibody inhibits tumor growth, fibrosis, angiogenesis, and immune cell remodeling in lung, pancreatic, and colorectal cancers.

Considering the limited efficacy of current therapies in lung, colorectal, and pancreatic cancers, innovative combination treatments with diverse mechanisms of action are needed to improve patients' outcomes. Chitinase-3 like-1 protein (CHI3L1) emerges as a versatile factor with significant implications in various diseases, particularly cancers, fostering an immunosuppressive tumor microenvironment for cancer progression. Therefore, pre-clinical validation is imperative to fully realize its potential in cancer treatment. We developed phage display-derived fully human monoclonal CHI3L1 neutralizing antibodies (nAbs) and verified the nAbs-antigen binding affinity and specificity in lung, pancreatic and colorectal cancer cell lines. Tumor growth signals, proliferation and migration ability were all reduced by CHI3L1 nAbs in vitro. Orthotopic or subcutaneous tumor mice model and humanized mouse model were established for characterizing the anti-tumor properties of two CHI3L1 nAb leads. Importantly, CHI3L1 nAbs not only inhibited tumor growth but also mitigated fibrosis, angiogenesis, and restored immunostimulatory functions of immune cells in pancreatic, lung, and colorectal tumor mice models. Mechanistically, CHI3L1 nAbs directly suppressed the activation of pancreatic stellate cells and the transformation of macrophages into myofibroblasts, thereby attenuating fibrosis. These findings strongly support the therapeutic potential of CHI3L1 nAbs in overcoming clinical challenges, including the failure of gemcitabine in pancreatic cancer.

Exploring conflict between caregiving and work for caregivers of elders with dementia: a cross-sectional, correlational study.

AIM: To report the moderating effects of work-related conditions and interactive family-care-giving variables, including mutuality and preparedness, on caregiver role strain and mental health for family caregivers of patients with dementia. BACKGROUND: Few studies have examined the interrelationships among caregivers' working conditions, care-giving dynamics and caregiver well-being. DESIGN: Cross-sectional, correlational study. METHODS: Data were collected by self-completed questionnaires from 176 primary family caregivers of patients with dementia in Taiwan from May 2005-January 2006. Caregiver role strain and mental health were analysed by multiple regressions using a hierarchical method to enter independent variables and two- and three-way interaction terms after controlling for caregiver age and gender, employment status, and work flexibility and the simple effect of each independent variable. RESULTS: More preparedness was associated with less role strain for family caregivers with less work/care-giving conflict. More care-giving demand was associated with poorer mental health only for caregivers with low work/care-giving conflict and with average and low preparedness, but not high preparedness. For family caregivers with less work/care-giving conflict, more preparedness decreased role strain and maintained mental health even when care-giving demand was high. CONCLUSION: These results provide a knowledge base for understanding complex family caregiver phenomena and serve as a guide for developing interventions. Future studies with longitudinal follow-ups are suggested to explore actual causal relationships.

An evaluation study of a dementia screening program in Taiwan: an application of the theory of planned behaviors.

A challenge facing dementia service providers is how to detect dementia early to facilitate timely intervention. This article reports findings of an evaluation study of a dementia-screening program in Taiwan utilizing the Theory of Planned Behaviors. We present the Short Portable Mental Status Questionnaire (SPMSQ) program rationale and examine the effects of this important health and social service intervention. Follow-up telephone interviews were completed by 108 respondents. Findings indicate that the SPMSQ program was successful in identifying suspected dementia. Results also show that the dementia-screening program contributed to an increase in medical service utilization and in unpaid informal care.

The Antitumor Effect of Caffeic Acid Phenethyl Ester by Downregulating Mucosa-Associated Lymphoid Tissue 1 via AR/p53/NF-κB Signaling in Prostate Carcinoma Cells.

Caffeic acid phenethyl ester (CAPE), a honeybee propolis-derived bioactive ingredient, has not been extensively elucidated regarding its effect on prostate cancer and associated mechanisms. The mucosa-associated lymphoid tissue 1 gene (MALT1) modulates NF-κB signal transduction in lymphoma and non-lymphoma cells. We investigated the functions and regulatory mechanisms of CAPE in relation to MALT1 in prostate carcinoma cells. In p53- and androgen receptor (AR)-positive prostate carcinoma cells, CAPE downregulated AR and MALT1 expression but enhanced that of p53, thus decreasing androgen-induced activation of MALT1 and prostate-specific antigen expressions. p53 downregulated the expression of MALT in prostate carcinoma cells through the putative consensus and nonconsensus p53 response elements. CAPE downregulated MALT1 expression and thus inhibited NF-κB activity in p53- and AR-negative prostate carcinoma PC-3 cells, eventually reducing cell proliferation, invasion, and tumor growth in vitro and in vivo. CAPE induced the ERK/JNK/p38/AMPKα1/2 signaling pathways; however, pretreatment with the corresponding inhibitors of MAPK or AMPK1/2 did not inhibit the CAPE effect on MALT1 blocking in PC-3 cells. Our findings verify that CAPE is an effective antitumor agent for human androgen-dependent and -independent prostate carcinoma cells in vitro and in vivo through the inhibition of MALT1 expression via the AR/p53/NF-κB signaling pathways.

Targeting protumor factor chitinase-3-like-1 secreted by Rab37 vesicles for cancer immunotherapy.

Background: Chitinase 3-like-1 (CHI3L1) is a secretion glycoprotein associated with the immunosuppressive tumor microenvironment (TME). The secretory mode of CHI3L1 makes it a promising target for cancer treatment. We have previously reported that Rab37 small GTPase mediates secretion of IL-6 in macrophages to promote cancer progression, whereas the roles of Rab37 in the intracellular trafficking and exocytosis of CHI3L1 are unclear. Methods: We examined the concentration of CHI3L1 in the culture medium of splenocytes and bone marrow derived macrophages (BMDMs) from wild-type or Rab37 knockout mice, and macrophage or T cell lines expressing wild type, active GTP-bound or inactive GDP-bound Rab37. Vesicle isolation, total internal reflection fluorescence microscopy, and real-time confocal microscopy were conducted. We developed polyclonal neutralizing-CHI3L1 antibodies (nCHI3L1 Abs) to validate the therapeutic efficacy in orthotopic lung, pancreas and colon cancer allograft models. Multiplex fluorescence immunohistochemistry was performed to detect the protein level of Rab37 and CHI3L1, and localization of the tumor-infiltrating immune cells in allografts from mice or tumor specimens from cancer patients. Results: We demonstrate a novel secretion mode of CHI3L1 mediated by the small GTPase Rab37 in T cells and macrophages. Rab37 mediated CHI3L1 intracellular vesicle trafficking and exocytosis in a GTP-dependent manner, which is abolished in the splenocytes and BMDMs from Rab37 knockout mice and attenuated in macrophage or T cell lines expressing the inactive Rab37. The secreted CHI3L1 activated AKT, ß-catenin and NF-κB signal pathways in cancer cells and macrophages to foster a protumor TME characterized by activating M2 macrophages and increasing the population of regulatory T cells. Our developed nCHI3L1 Abs showed the dual properties of reducing tumor growth/metastases and eliciting an immunostimulatory TME in syngeneic orthotopic lung, pancreas and colon tumor models. Clinically, high plasma level or intratumoral expression of CHI3L1 correlated with poor survival in 161 lung cancer, 155 pancreatic cancer and 180 colon cancer patients. Conclusions: These results provide the first evidence that Rab37 mediates CHI3L1 secretion in immune cells and highlight nCHI3L1 Abs that can simultaneously target both cancer cells and tumor microenvironment.

Caffeic acid phenethyl ester inhibits the growth of bladder carcinoma cells by upregulating growth differentiation factor 15.

BACKGROUND: Caffeic acid phenethyl ester (CAPE), a bioactive component of propolis, has beneficial effects on cancer prevention. Growth differentiation factor 15 (GDF15) is an antitumor gene of bladder cancer. Therefore, this study investigated the anti-cancer effect of CAPE on bladder carcinoma cells and related mechanisms. METHODS: The expressions of GDF15, N-myc downstream-regulated gene 1 (NDRG1), and maspin, and the activations of extracellular signal regulated kinase (ERK), c-jun Nterminal kinase (JNK), p38, and 50 adenosine monophosphate-activated protein kinase (AMPK) α1/2 in human bladder cells after gene transfection or knockdown were determined by immunoblot, real-time reverse transcriptase-polymerase chain reaction (RT-qPCR), and reporter assays. The assays of 5-ethynyl-2'-deoxyuridine (EdU), CyQUANT cell proliferation, and Matrigel invasion, and the xenograft animal study were used to assess the cell proliferation, invasion, and tumorigenesis. RESULTS: GDF15 expression in epithelial cells was negatively correlated with neoplasia in vitro. Also, GDF15 exhibits in bladder fibroblasts and smooth muscle cells. CAPE-induced expressions of NDRG1 and maspin decreased cell proliferation and invasion of bladder carcinoma cells in a GDF15-dependent manner in vitro. The xenograft animal study suggesting CAPE attenuated tumor growth in vivo. CAPE increased phosphorylation of ERK, JNK, p38, and AMPKα1/2 to modulate the GDF15 expressions. Pretreatments with ERK, JNK, or p38 inhibitors partially inhibited the CAPE effects on the inductions of GDF15, NDRG1, or maspin. Knockdown of AMPKα1/2 attenuated the CAPE-induced GDF15 expression and cell proliferation in bladder carcinoma cells. CONCLUSIONS: Our findings indicate that CAPE is a promising agent for anti-tumor growth in human bladder carcinoma cells via the upregulation of GDF15.

Surgery for Xanthogranulomatous Pyelonephritis: A Comparison of Midline Transperitoneal and Flank Retroperitoneal Laparotomy Approaches to Nephrectomy.

Xanthogranulomatous pyelonephritis (XGP) is a rare inflammatory disease often associated with high morbidity and mortality. Whether the midline transperitoneal or the flank retroperitoneal approach is superior remains unknown. We searched through pathology databases and reviewed 86 patients with an XGP diagnosis from 2000 to 2021 at our institution. After the patients who did not meet the inclusion criteria were excluded, 35 patients who had undergone nephrectomy through the midline transperitoneal or the flank retroperitoneal laparotomy approach were recruited. Nine (25.71%) of the thirty-five patients underwent nephrectomy through a midline approach, whereas twenty-six (74.29%) received a flank approach. Patients in the midline approach group had a longer surgical time (p = 0.03) than those in the flank approach group. In addition, patients in the flank approach group took less time after surgery to resume oral intake than those in the midline approach group (p = 0.01). No significant differences in the rates of intraoperative and postoperative complications such as peritonitis or intraabdominal infection were observed between the groups. For the patients with XGP who are good candidates for surgery, nephrectomy is a relatively safe surgical treatment method. Both surgical methods produced favorable surgical outcomes, and the patients who received these methods had similar complication rates.

Comparison of Outcome and Quality of Life Between Thulium Laser (VelaTM XL) Enucleation of Prostate and Bipolar Transurethral Enucleation of the Prostate (B-TUEP).

BACKGROUND AND PURPOSE: In this study, we compared patient outcomes between the 120-W thulium laser (Vela™XL) prostate enucleation (ThuLEP) and bipolar transurethral enucleation of the prostate (B-TUEP) techniques. METHODS: We excluded patients with concomitant prostate cancer and bladder cancer and prospectively analyzed patients with benign prostatic obstruction (BPO) who underwent ThuLEP and B-TUEP from October 2018 to January 2021 in our institution. Patients' demographics, comorbidities, prostate volumes, prostate-specific antigen (PSA) levels, and International Prostate Symptoms Score (IPSS) were recorded. Perioperative outcomes including intraoperative blood loss, prostate resection percentage of the transition zone, postoperative pain score (numeric rating scale, NRS), complications, changes in postoperative uroflowmetry parameters, IPSS, and the rate of reuse of BPH medications were also evaluated. RESULTS: The data of a total of 111 patients (ThuLEP: 49, B-TUEP: 62) met the inclusion criteria were collected and analyzed prospectively. Our results revealed no significant differences between ThuLEP and B-TUEP in terms of operation time, prostate tissue enucleated, and days of hospitalization. However, patients in the ThuLEP group reported less pain after surgery than those in the B-TUEP group, and a higher proportion of patients in the B-TUEP group returned to the emergency department due to complications within one month postoperatively, with hematuria being the main cause. No significant differences were observed between the groups in changes in uroflowmetry parameters and IPSS at 2 weeks, 3 months, and 6 months postoperatively. CONCLUSION: The efficacy of ThuLEP was comparable to that of B-TUEP in terms of maximal flow rate, voiding volume, IPSS, and quality of life. ThuLEP also had several advantages over B-TUEP, including less blood loss and less postoperative pain. Therefore, ThuLEP can be considered a treatment of choice for BPH/bladder outlet obstruction, specifically for patients with a bleeding tendency and fear of pain.

Reconciling work and family caregiving among adult-child family caregivers of older people with dementia: effects on role strain and depressive symptoms.

AIMS: This paper is a report of a study that examined the effects of work demands, including employment status, work inflexibility and difficulty reconciling work and family caregiving, on role strain and depressive symptoms of adult-child family caregivers of older people with dementia. BACKGROUND: Family caregivers also employed for pay are known to be affected by work demands, i.e. excessive workload and time pressures. However, few studies have shown how these work demands and reconciliation between work and family caregiving influence caregivers' role strain and depressive symptoms. METHOD: For this cross-sectional study, secondary data were analysed for 119 adult-child family caregivers of older people with dementia in Taiwan using hierarchical multiple regression. RESULTS: After adjusting for demographic characteristics, resources and role demands overload, family caregivers with full-time jobs (ß=0.25, P<0.01) and more difficulty reconciling work and caregiving roles (ß=0.36, P<0.01) reported significantly more role strain than family caregivers working part-time or unemployed. Family caregivers with more work inflexibility reported more depressive symptoms (ß=0.29, P<0.05). CONCLUSION: Work demands affected family caregivers' role strain and depressive symptoms. Working full-time and having more difficulty reconciling work and caregiving roles predicted role strain; work inflexibility predicted depressive symptoms. These results can help clinicians identify high-risk groups for role strain and depression. Nurses need to assess family caregivers for work flexibility when screening for high-risk groups and encourage them to reconcile working with family-care responsibilities to reduce role strain.

Risk Factor of De Novo Urgency and Urge Incontinence After Autologous Fascia Pubovaginal Sling.

INTRODUCTION: Pubovaginal sling is an efficient and safe procedure for stress urinary incontinence without the complications of synthetic sling. Urine retention and de novo urgency are bothersome aftermath of this procedure. We aim to identify potential risk factors for de novo urgency after autologous pubovaginal sling. METHODS: From 2013 to 2016, 347 patients underwent autologous pubovaginal sling. Age, BMI, pelvic irradiation, use of anticholinergic medication, previous vaginal related surgical histories, "over-tight" technique, and concomitant surgeries were examined for potential risk factors. De novo urgency/urge incontinence was defined as treatment (medication, botulinum toxin injection, sacral neuromodulation) for urge postoperatively and was not noted before surgery. Chi-square and fisher's exact tests were used as statistical analysis. RESULTS: A total of 109 patients underwent autologous rectus fascia pubovaginal sling, after excluding status post urethral diverticulectomy, concomitant diverticulectomy, and concomitant abdominal surgery. Twenty-three (21.1%) patients were treated for de novo urge/urge incontinence, 18 (78.2%) with anticholinergic, 4 (17.3%) with botox injection and 2 (8.69%) with sacral neuromodulation. None but prior pelvic organ prolapse surgery was associated with developing de novo urge/urge incontinence (p=0.026). DISCUSSION: Patients with prior pelvic organ prolapse surgery were more likely to be at risk of de novo urgency after autologous pubovaginal sling. This study provided more information for preoperative consultation for patients undergoing incontinence surgery.

Converged Rab37/IL-6 trafficking and STAT3/PD-1 transcription axes elicit an immunosuppressive lung tumor microenvironment.

Background: Increased IL-6 level, M2 macrophages and PD-1+CD8+ T cells in tumor microenvironments (TME) have been identified to correlate with resistance to checkpoint blockade immunotherapy, yet the mechanism remains poorly understood. Rab small GTPase-mediated trafficking of cytokines is critical in immuno-modulation. We have previously reported dysregulation of Rab37 in lung cancer cells, whereas the roles of Rab37 in tumor-infiltrating immune cells and cancer immunotherapy are unclear. Methods: The tumor growth of the syngeneic mouse allograft in wild type or Rab37 knockout mice was analyzed. Imaging analyses and vesicle isolation were conducted to determine Rab37-mediated IL-6 secretion. STAT3 binding sites at PD-1 promoter in T cells were identified by chromatin immunoprecipitation assay. Multiplex fluorescence immunohistochemistry was performed to detect the protein level of Rab37, IL-6 and PD-1 and localization of the tumor-infiltrating immune cells in allografts from mice or tumor specimens from lung cancer patients. Results: We revealed that Rab37 regulates the secretion of IL-6 in a GTPase-dependent manner in macrophages to trigger M2 polarization. Macrophage-derived IL-6 promotes STAT3-dependent PD-1 mRNA expression in CD8+ T cells. Clinically, tumors with high stromal Rab37 and IL-6 expression coincide with tumor infiltrating M2-macrophages and PD1+CD8+ T cells that predicts poor prognosis in lung cancer patients. In addition, lung cancer patients with an increase in plasma IL-6 level are found to be associated with immunotherapeutic resistance. Importantly, combined blockade of IL-6 and CTLA-4 improves survival of tumor-bearing mice by reducing infiltration of PD1+CD8+ T cells and M2 macrophages in TME. Conclusions: Rab37/IL-6 trafficking pathway links with IL-6/STAT3/PD-1 transcription regulation to foster an immunosuppressive TME and combined IL-6/CTLA-4 blockade therapy exerts potent anti-tumor efficacy.

The Clinical Experiences of Urine Metabolomics of Genitourinary Urothelial Cancer in a Tertiary Hospital in Taiwan.

Few studies have addressed the impact of diagnostic urine metabolites and the clinical outcomes associated with genitourinary urothelial (GU) cancer to date. Furthermore, longitudinal analysis of the dynamics of urine metabolites contributing to the detection of GU cancer has not yet been fully investigated; therefore, the discovery of novel diagnostic urine biomarkers is of enormous interest. We explored the correlation of the urine metabolomic profiles to GU cancers. The aqueous metabolites of the GU cancer and the control were also identified and analyzed through high-resolution1H nuclear magnetic resonance (NMR) spectroscopy. Compared with the control, the urine metabolites of the tumor were studied in relation to changes over time in a linear mixed model for repeated measures. The urine metabolites of sixty-three (44 male and 19 female) patients with GU cancers were systemically analyzed. The urine metabolite profile in GU cancer was significantly higher than those in the control group (p<0.05). Sevenurine metabolites including histidine, propylene glycol, valine, leucine, acetylsalicylate, glycine, and isoleucine as well as other pathways were identified statistically and were significantly associated with GU cancer detection with longitudinal analysis. We discovered that histidine, propylene glycol, valine, leucine, acetylsalicylate, glycine, isoleucine, succinic acid, lysine2-aminobutyric acid, and acetic acid are involved significantly in all types of male patients in whom the type (upper tract) of urine metabolites were found to be statistically significant compared with the control. We did not find any statistical significance in urine biomarkers between female and male patients. However, a statistically insignificant correlation was found among the grade and stage with the metabolites.

Clinical Outcome of Endoscopic Enucleation of the Prostate Compared With Robotic-Assisted Simple Prostatectomy for Prostates Larger Than 80 cm3 in Aging Male.

This study investigated and compared the surgical outcomes of using endoscopic enucleation (thulium: YAG laser and bipolar plasma; ThuLEP) with robotic-assisted simple prostatectomy (RASP) in the treatment of prostates larger than 80 cm3. Records were obtained for the period from January 2014 to December 2020 for selected patients with BPO who underwent RASP, ThuLEP, or bipolar transurethral enucleation of the prostate (B-TUEP). Patients were excluded if they had active malignant disease, neurogenic bladder, lower urinary tract syndrome for reasons other than BPO, and a history of prostate surgery. Data of 396 patients who underwent B-TUEP, ThuLEP, and RASP were examined. A total of 112 patients met the including criteria, 85 of whom (B-TUEP: 29; ThuLEP: 41; RASP: 15) completed the final visit. The mean operation time and duration of postoperative hospital stays in the RASP group were significantly longer than those of the B-TUEP and ThuLEP groups. Only 1 patient in the RASP group required blood transfusion. The RASP group was superior to the other groups in voiding improvement including Qmax and IPSS voiding score. The pain score of the ThuLEP group after surgery was significantly lower than that of the other two groups during hospitalization, whereas the QoL scores were identical between the three groups at 2 weeks, 3 months, and 6 months post operation. The rates of returning to ER within the first postoperative month did not differ significantly between the three groups, and all the reasons for return involved minor complications that required no additional invasive treatment. These three surgical methods (B-TUEP, ThuLEP, and RASP) are all effective and safe for treating prostates larger than 80 cm3, with each having its particular advantages. B-TUEP requires the shortest operation time, ThuLEP causes the lowest postoperative pain, and RASP results in superior voiding function improvement.

Prostate-Specific Antigen Velocity Predicts Surgical Outcome of Thulium Laser Enucleation of the Prostate.

Background: We determined the effect of prostate-specific antigen velocity (PSAV) on the surgical outcome of thulium laser enucleation of the prostate (ThuLEP) in patients with benign prostatic hyperplasia (BPH). Methods: A retrospective review was performed of prospectively collected data of patients with BPH who underwent ThuLEP at any time from 2017 to 2019. Patients who had undergone BPH surgery or had prostate cancer previously were excluded, and patients with prostate-specific antigen (PSA) > 4 ng/ml were examined through transrectal ultrasound-guided prostate biopsy to rule out prostatic malignancy. Furthermore, patients were excluded if prostatic malignancy was diagnosed during postsurgery follow-up. Results: The PSA level, International Prostate Symptom Score (IPSS), and quality of life (QoL) of 27 male patients at 3 and 15 months postsurgery differed significantly from those at presurgery; the maximum flow rate (Qmax) and postvoid residual (PVR) significantly differed between 3 months postsurgery and presurgery; and 22 and 5 patients had good to excellent and fair to poor outcomes, respectively, at 15 months postsurgery. Patients were divided into two groups (fair and poor vs. good and excellent outcomes at 15 months postsurgery), which significantly differed with respect to PSAV at 3 months postsurgery (P = 0.04), IPSS presurgery (P < 0.02), surgical length (P = 0.01), and hospitalization duration (P = 0.04). In a receiver operating characteristic (ROC) analysis, the optimal cutoff value of PSAV of -0.52 ng/ml characterized effectiveness at 15 months after ThuLEP, and the area under the curve (AUC), sensitivity, and specificity were 0.82 (P < 0.02), 0.80, and 0.82, respectively. For PSAV < -0.52 and ≥-0.52 ng/ml, the percentages of reduction for IPSS, QoL, Qmax, and PVR were -78.6 and -71.4%, -33.3 and 0.0%, 94.4 and 40.0%, and -85.1 and -38.7%, respectively. Conclusions: Postsurgical PSAV was positively correlated with surgical success, and the PSAV cutoff was -0.52 ng/ml. PSAV can, thus, be used to guide the postsurgical follow-up treatment at 3 months after BPH surgery.