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.

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.

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.

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.

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.

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.

Mucosa-Associated Lymphoid Tissue 1 Is an Oncogene Inducing Cell Proliferation, Invasion, and Tumor Growth via the Upregulation of NF-κB Activity in Human Prostate Carcinoma Cells.

Prostate cancer is one of the most common seen malignancies and the leading cause of cancer-related death among men. Given the importance of early diagnosis and treatment, it is worth to identify a potential novel therapeutic target for prostate cancer. Mucosa-associated lymphoid tissue 1 (MALT1) is a novel gene involved in nuclear factor κB (NF-κB) signal transduction by acting as an adaptor protein and paracaspase, with an essential role in inflammation and tumorigenesis in many cancers. This study investigated the functions and the potential regulatory mechanisms of MALT1 in the human prostate cancer cells. We found that MALT1 is abundant in prostate cancer tissues. MALT1 facilitated NF-κB subunits (p50 and p65) nuclear translocation to induce gene expression of interleukin 6 (IL-6) and C-X-C motif chemokine 5 (CXCL5) in prostate carcinoma cells. MALT1 promoted cell proliferation, invasion, and tumor growth in vitro and in vivo. MALT1 enhanced NF-κB activity in prostate carcinoma cells; moreover, NF-κB induced MALT1 expression determined by reporter and immunoblot assays, implying there is a positive feedback loop between MALT1 and NF-κB. In conclusion, MALT1 is a NF-κB-induced oncogene in the human prostate carcinoma cells.

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.

Effect of ureteral calculus in outpatients receiving semirigid ureteroscope laser lithotripsy.

The surgical outcomes of patients with single ureteral stones who had undergone ureteroscopic Holmium laser lithotripsy as outpatients and compare them with those of patients who had received the same procedure as inpatients. Records were obtained from January 2012 to December 2016 for selected patients who had undergone the above mentioned procedure at our institution. Patients were excluded if their ECOG performance status was ≥2, presented with multiple stones or concomitant renal stones, had histories of cancer or congenital urinary system abnormalities, or had undergone urinary system reconstruction surgery. Patients could decide whether to receive the procedure as an outpatient or inpatient. All surgeries were performed by a single surgeon. Patients preoperative, operative, and postoperative data were recorded. The clinical results, such as urinary tract infection, analgesic requirement, rate of returning to the emergency room, stone clearance, surgical complications, and medical expenditure for the treatment courses were analyzed and compared between the 2 cohorts. In total, 303 patients met the inclusion criteria. Among them, 119 patients decided to receive ureteroscopic laser lithotripsy as outpatients, whereas 184 decided to be inpatients. The outpatient cohort was younger (P < .001), had smaller stone diameters (P < .001), and fewer comorbidity factors (P = .038). Patients with a history of stone manipulation favored receiving the procedure under admission (P < .001). After 1:1 propensity score matching, no significant differences were discovered between the cohorts with regard to operative time, rate of lithotripsy failure, and operative complications. Furthermore, rates of stone clearance, post-op urinary tract infection, analgesic requirement, and returning to the emergency room were comparable between the 2 groups. However, the medical expenditure was significantly lower in the outpatient cohort (P < .001). Our data revealed that outpatient ureteroscopic lithotripsy with a Holmium laser was more economical compared with the inpatient group and achieved favorable outcomes for patients with a single ureteral stone.

Clinical outcome of transurethral enucleation of the prostate using the 120-W thulium Laser (Vela™ XL) compared to bipolar transurethral resection of the prostate (TURP) in aging male.

This study compared the surgical outcomes of the 120-W Thulium laser (Vela™ XL) enucleation of the prostate and bipolar transurethral resection of the prostate (TURP) in terms of efficacy, safety, and improvements of quality of life (QoL) in patients with benign prostate hyperplasia (BPH). Records were obtained from January 2014 to September 2018 for selected patients with symptomatic BPH who underwent 120-W Thulium laser (Vela™XL) prostate enucleation and bipolar TURP in our institution. All the patients selected met the surgical criteria for TURP and had received medical treatment for at least 3 months. Patients were excluded if their ECOG performance status was >1, if they had active malignant disease, of if they had a history of prostate surgery or reconstruction surgery of the urinary system. Patients decided which treatment option would be performed. Both the procedures were conducted by a single surgeon. Clinical outcomes such as changes in the International Prostate Symptom Score (IPSS) score, urodynamic parameters, drug consumption, pain scores, and QoL were evaluated. The rate of urinary tract infection, recatheterization, additional analgesic requirement, return to the emergency department for treatment, and other surgical complications was analyzed and compared between the two cohorts. A total of 276 patients met the inclusion criteria. Among them, 141 patients received bipolar TURP, where as 135 decided to receive laser vaporesection. No significant difference was observed in age, PSA level, prostate volume, and comorbidities between the two cohorts. Pre-operative (pre-op) urodynamic parameters were also identical, except that the laser surgery group had a higher rate of admission with a urinary catheter (24.4% vs. 14.2%, p=0.044). The operating time was longer in the laser surgery group (79.3 minutes vs. 62.4 minutes, p<0.001). However, enucleation using the Thulium laser was superior to bipolar TURP in terms of post-operative (post-op) pain status, including the numeric rating scale of pain, rate of additional narcotic use, and oral analgesic requirement. Compared with bipolar TURP, laser enucleation achieved a higher improvement in the QoL score at post-op follow-up at 2 weeks and 3 months. Nevertheless, the complication rate, changes in IPSS score, Qmax, and post-op medication-free survival were statistically identical in the two cohorts. Our data revealed that compared with bipolar TURP, 120-W Thulium laser (Vela™ XL) enucleation of the prostate achieved lower post-op pain and higher improvement in the short-term QoL of patients after surgery.

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.

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.

Allergic rhinitis and the associated risk of nocturnal enuresis in children: a population-based cohort study.

BACKGROUND: Despite controversy, an association between allergy and nocturnal enuresis (NE) has been reported for almost a century. Allergic rhinitis (AR)-associated sleep-disordered breathing frequently results in microarousals during sleep, decreased sleep efficiency, and change in sleep pattern and behavior. NE is a common sleep disorder in children. Hence, this study aimed to investigate the incidence and risk of NE in children with AR. METHODS: A population-based cohort study was conducted among 327,928 children with AR and 327,601 non-AR controls between 2000 and 2012 in Taiwan. By the end of 2012, the incidence of NE in both cohorts, and the AR-to-non-AR cohort hazard ratios (HRs) were measured. RESULTS: The adjusted HR of NE during the study period was 1.7-fold higher in the AR cohort compared to the non-AR cohort. The risk was greater for boys, children younger than 6 years old, those with comorbidities of asthma, atopic dermatitis, and attention deficit/hyperactivity disorder (ADHD), and those who had more than 5 AR-related medical visits per year. The risk of NE in the AR cohort decreased with follow-up time and was the highest within the first year after AR diagnosis. CONCLUSION: Children with AR had a higher incidence and subsequent risk of NE. The risk of NE was greater for boys, younger children, and those with more frequent health utilization for AR symptoms.

Utilization of Chinese herbal medicine and its association with the risk of fracture in patients with Parkinson's disease in Taiwan.

ETHNOPHARMACOLOGICAL RELEVANCE: Traditional Chinese medicine (TCM) has been used for over two thousand years to treat motor impairments corresponding to the clinical manifestations of Parkinson's disease (PD). AIM OF THE STUDY: This study aimed to investigate the prescription of Chinese herbal medicine (CHM) for the management of PD and further determine whether CHM can improve motor function and decrease the risk of incident fracture. MATERIALS AND METHODS: Patients older than 40 years newly diagnosed with PD between January 1997 and December 2010 were selected from the National Health Insurance Research Database (NHIRD) and followed up until the end of 2013. We used 1:1 frequency matching by age, sex, index year, and initial diagnostic year to compare the TCM users and non-TCM users. We used a Cox regression model and the Kaplan-Meier method to estimate the risk of developing fracture among the TCM and non-TCM users. RESULTS: In total, 7197 patients older than 40 years were newly diagnosed with PD between 1997 and 2010 in Taiwan. Among these patients, 3456 were TCM users, and 3730 were non-TCM users. We compared 2007 PD patients with comparable demographic characteristics and comorbidity profiles between the two cohorts. During the follow-up period, compared with the non-TCM cohort, fewer patients in the TCM cohort had incident fractures (adjusted hazard ratio: 0.5, 95% CI: 0.44-0.56). The cumulative incidence of fracture was lower in the TCM cohort (log-rank test, p < 0.0001). Shi-Chang-Pu (Acorus gramineus Aiton), Yuan-Zhi (Polygala tenuifolia Willd), Bei-Mu (Fritillaria cirrhosa D. Don), Hai-Piao-Xiao (Sepiella maindronide Rochebrune; Sepia esculenta Hoyle), and Tian-Ma (Gastrodia elata Blume) constituted the core Chinese herbal medicine prescriptions used to treat PD patients. CONCLUSIONS: The present study identified the core prescription pattern for the management of PD in Taiwan. Complementary CHM therapy was associated with a reduced risk of fracture in PD patients.

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.

An open-label, prospective interventional study of the tolerability and efficacy of 0.4 mg oral tamsulosin oral controlled absorption system in men with lower urinary tract symptoms associated with benign prostatic hyperplasia who are unsatisfied with treatment with 0.2 mg tamsulosin.

PURPOSE: The aim of this study was to investigate the efficacy and tolerability of switching from 0.2 mg tamsulosin to 0.4 mg tamsulosin oral controlled absorption system (OCAS) over a 12-week period in Taiwanese men with lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH). PATIENTS AND METHODS: Taiwanese male patients who were dissatisfied with treatment with 0.2 mg tamsulosin were enrolled in this clinical study and switched to 0.4 mg tamsulosin OCAS. Efficacy was assessed over a 12-week period by an International Prostate Symptom Score (IPSS) questionnaire and analysis of urinary flow by uroflowmetry. RESULTS: A statistically significant improvement was observed in total IPSS scores from baseline (14.94±7.41, moderate) to 12 weeks (7.36±5.77, mild) in 81 patients who were switched from 0.2 to 0.4 mg tamsulosin OCAS (P<0.001). The IPSS subscores for storage, voiding, nocturia, and quality of life (QOL) were also significantly improved over the 12-week period. Uroflowmetry analysis demonstrated significantly increased maximum flow rate, average flow rate, and mean voided volume from baseline to the end of the 12-week period. The 0.4 mg tamsulosin OCAS dose was well tolerated, with only mild dizziness (five patients) and headache (two patients) as the most frequent adverse events. No clinically significant reduction was observed in blood pressure or vital signs. CONCLUSION: Treatment with 0.4 mg tamsulosin OCAS in Taiwanese men with LUTS associated with BPH who were dissatisfied with 0.2 mg tamsulosin significantly improved IPSS scores, urinary flow, and QOL and was well tolerated, suggesting that this should be the recommended dose offered to Taiwanese male patients.