Fernando J Garcia-Marques, Elissa Zakrasek, Abel Bermudez, Alexandra L Polasko, Shiqin Liu, Tanya Stoyanova, James D Brooks, John Lavelle, Sharon J Pitteri
After spinal cord injury (SCI), use chronic urinary catheters for bladder management is common, making these patients especially vulnerable to catheter-associated complications. Chronic catheterization is associated with bacterial colonization and frequent catheter-associated urinary tract infections (CAUTI). One determinant of infection success and treatment resistance is production of catheter-associated biofilms, composed of microorganisms and host- and microbial-derived components. To better understand the biofilm microenvironment, we performed proteomics analysis of catheter-associated biofilms and paired urine samples from four people with SCI with chronic indwelling urinary catheters. We developed a novel method for the removal of adhered cellular components on catheters that contained both human and microbial homologous proteins. Proteins from seven microbial species were identified including: Escherichia coli, Klebsiella species (spp), Enterococcus spp, Proteus mirabilis, Pseudomonas spp, Staphylococcus spp, and Candida spp. Peptides identified from catheter biofilms were assigned to 4,820 unique proteins, with 61% of proteins assigned to the biofilm-associated microorganisms, while the remainder were human-derived. Contrastingly, in urine, only 51% were assigned to biofilm-associated microorganisms and 4,554 proteins were identified as a human-derived. Of the proteins assigned to microorganisms in the biofilm and paired urine, Enterococcus, Candida spp, and P. mirabilis had greater associations with the biofilm phase, whereas E. coli and Klebsiella had greater associations with the urine phase, thus demonstrating a significant difference between the urine and adhered microbial communities. The microbial proteins that differed significantly between the biofilm and paired urine samples mapped to pathways associated with amino acid synthesis, likely related to adaptation to high urea concentrations in the urine, and growth and protein synthesis in bacteria in the biofilm. Human proteins demonstrated enrichment for immune response in the catheter-associated biofilm. Proteomic analysis of catheter-associated biofilms and paired urine samples has the potential to provide detailed information on host and bacterial responses to chronic indwelling urinary catheters and could be useful for understanding complications of chronic indwelling catheters including CAUTIs, urinary stones, and catheter blockages.
{"title":"Proteomics analysis of urine and catheter-associated biofilms in spinal cord injury patients.","authors":"Fernando J Garcia-Marques, Elissa Zakrasek, Abel Bermudez, Alexandra L Polasko, Shiqin Liu, Tanya Stoyanova, James D Brooks, John Lavelle, Sharon J Pitteri","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>After spinal cord injury (SCI), use chronic urinary catheters for bladder management is common, making these patients especially vulnerable to catheter-associated complications. Chronic catheterization is associated with bacterial colonization and frequent catheter-associated urinary tract infections (CAUTI). One determinant of infection success and treatment resistance is production of catheter-associated biofilms, composed of microorganisms and host- and microbial-derived components. To better understand the biofilm microenvironment, we performed proteomics analysis of catheter-associated biofilms and paired urine samples from four people with SCI with chronic indwelling urinary catheters. We developed a novel method for the removal of adhered cellular components on catheters that contained both human and microbial homologous proteins. Proteins from seven microbial species were identified including: <i>Escherichia coli, Klebsiella species (spp), Enterococcus spp, Proteus mirabilis, Pseudomonas spp, Staphylococcus spp</i>, and <i>Candida spp</i>. Peptides identified from catheter biofilms were assigned to 4,820 unique proteins, with 61% of proteins assigned to the biofilm-associated microorganisms, while the remainder were human-derived. Contrastingly, in urine, only 51% were assigned to biofilm-associated microorganisms and 4,554 proteins were identified as a human-derived. Of the proteins assigned to microorganisms in the biofilm and paired urine, <i>Enterococcus, Candida spp</i>, and <i>P. mirabilis</i> had greater associations with the biofilm phase, whereas <i>E. coli</i> and <i>Klebsiella</i> had greater associations with the urine phase, thus demonstrating a significant difference between the urine and adhered microbial communities. The microbial proteins that differed significantly between the biofilm and paired urine samples mapped to pathways associated with amino acid synthesis, likely related to adaptation to high urea concentrations in the urine, and growth and protein synthesis in bacteria in the biofilm. Human proteins demonstrated enrichment for immune response in the catheter-associated biofilm. Proteomic analysis of catheter-associated biofilms and paired urine samples has the potential to provide detailed information on host and bacterial responses to chronic indwelling urinary catheters and could be useful for understanding complications of chronic indwelling catheters including CAUTIs, urinary stones, and catheter blockages.</p>","PeriodicalId":7438,"journal":{"name":"American journal of clinical and experimental urology","volume":"11 3","pages":"206-219"},"PeriodicalIF":1.2,"publicationDate":"2023-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10333135/pdf/ajceu0011-0206.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9871949","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ezidin G Kaddumi, Ali Al Khader, Abdul-Fattah S Fararjeh, Alaa A Abusamhadaneh
Background: The involvement of the vagus nerve in the supraspinal neural circuits that control the urinary bladder function, especially during pathological conditions, became increasingly evident. However, the role of brainstem areas in these circuits is not studied yet.
Methods: In the present study, using c-fos immunohistochemistry, the roles of the vagus nerve to the responses of the reticular formation to cystometry in cyclophosphamide-treated rats were investigated.
Results: Cyclophosphamide treatment significantly increased the c-fos expression in the lateral reticular nucleus (LRt), lateral paragigantocellular nucleus (LPGi), caudal part of the ventrolateral reticular nucleus (CVL), and gigantocellular reticular nucleus (Gi) following cystometry. However, cyclophosphamide treatment didn't have significant effect on c-fos expression in ventrolateral reticular nucleus (VL), rostral part of VL (RVL), raphe pallidus nucleus (RPa), and raphe obscurus nucleus (Rob). Vagotomy significantly demolished the effect of cyclophosphamide in the LRt and LPGi areas without having any significant effect on other reticular formation areas. Whereas, in comparison to normal animals, the vagotomised animals didn't show any significant changes in c-fos expression.
Conclusion: The results of this study demonstrate the involvement of the reticular formation areas, particularly the ventral part, in processing urinary bladder function under cystitis condition. It also demonstrates the contribution of the vagus nerve in these processes.
{"title":"The effect of vagotomy on c-fos expression in the reticular formation areas following cystometry in cyclophosphamide-induced cystitis in rats.","authors":"Ezidin G Kaddumi, Ali Al Khader, Abdul-Fattah S Fararjeh, Alaa A Abusamhadaneh","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Background: </strong>The involvement of the vagus nerve in the supraspinal neural circuits that control the urinary bladder function, especially during pathological conditions, became increasingly evident. However, the role of brainstem areas in these circuits is not studied yet.</p><p><strong>Methods: </strong>In the present study, using c-fos immunohistochemistry, the roles of the vagus nerve to the responses of the reticular formation to cystometry in cyclophosphamide-treated rats were investigated.</p><p><strong>Results: </strong>Cyclophosphamide treatment significantly increased the c-fos expression in the lateral reticular nucleus (LRt), lateral paragigantocellular nucleus (LPGi), caudal part of the ventrolateral reticular nucleus (CVL), and gigantocellular reticular nucleus (Gi) following cystometry. However, cyclophosphamide treatment didn't have significant effect on c-fos expression in ventrolateral reticular nucleus (VL), rostral part of VL (RVL), raphe pallidus nucleus (RPa), and raphe obscurus nucleus (Rob). Vagotomy significantly demolished the effect of cyclophosphamide in the LRt and LPGi areas without having any significant effect on other reticular formation areas. Whereas, in comparison to normal animals, the vagotomised animals didn't show any significant changes in c-fos expression.</p><p><strong>Conclusion: </strong>The results of this study demonstrate the involvement of the reticular formation areas, particularly the ventral part, in processing urinary bladder function under cystitis condition. It also demonstrates the contribution of the vagus nerve in these processes.</p>","PeriodicalId":7438,"journal":{"name":"American journal of clinical and experimental urology","volume":"11 1","pages":"40-49"},"PeriodicalIF":1.5,"publicationDate":"2023-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10009307/pdf/ajceu0011-0040.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9122061","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Renyuan Zhang, Shalini Singh, Chunliu Pan, Bo Xu, Jon Kindblom, Kevin H Eng, John J Krolewski, Kent L Nastiuk
Benign prostatic hyperplasia (BPH) is a non-neoplastic proliferative disease producing lower urinary tract symptoms related to the resulting enlarged prostate. BPH is pathologically characterized by hyperplastic growth in both epithelial and stromal compartments. Androgen signaling is essential for prostate function and androgen blockade is the second-line medical therapy to relieve symptoms of BPH. Here we examined the prostates of probasin promoter-driven prolactin (Pb-PRL) transgenic mice, a robust model of BPH that spontaneously develops prostate enlargement, to investigate prostate regression in response to surgical castration. Serial ultrasound imaging demonstrated very uniform self-limited growth of Pb-PRL prostate volume that is consistent with the benign, limited cellular proliferation characteristic of BPH and that contrasts with the highly variable, exponential growth of murine prostate cancer models. Castration elicited only a partial reduction in prostate volume, relative to castration-induced regression of the normal prostate gland. The anti-androgen finasteride induced a diminished reduction of Pb-PRL prostate volume versus castration. The limited extent of Pb-PRL mouse prostate volume regression correlated with the initial volume of the stromal compartment, suggesting a differential sensitivity of the epithelial and stromal compartments to androgen withdrawal. Indeed, two-dimensional morphometric analyses revealed a distinctly reduced rate of regression for the stromal compartment in Pb-PRL mice. The myofibroblast component of the Pb-PRL prostate stroma appeared normal, but the stromal compartment contained more fibroblasts and extracellular collagen deposition. Like normal prostate, the rate of regression of the Pb-PRL prostate was partially dependent on TGFß and TNF signaling, but unlike the normal prostate, the extent of castration-induced regression was not affected by TGFß or TNF blockade. Our studies show that androgen deprivation can effectively reduce the overall volume of hyperplastic prostate, but the stromal compartment is relatively resistant, suggesting additional therapies might be required to offer an effective treatment for the clinical manifestations of BPH.
{"title":"Rate of castration-induced prostate stroma regression is reduced in a mouse model of benign prostatic hyperplasia.","authors":"Renyuan Zhang, Shalini Singh, Chunliu Pan, Bo Xu, Jon Kindblom, Kevin H Eng, John J Krolewski, Kent L Nastiuk","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Benign prostatic hyperplasia (BPH) is a non-neoplastic proliferative disease producing lower urinary tract symptoms related to the resulting enlarged prostate. BPH is pathologically characterized by hyperplastic growth in both epithelial and stromal compartments. Androgen signaling is essential for prostate function and androgen blockade is the second-line medical therapy to relieve symptoms of BPH. Here we examined the prostates of probasin promoter-driven prolactin (Pb-PRL) transgenic mice, a robust model of BPH that spontaneously develops prostate enlargement, to investigate prostate regression in response to surgical castration. Serial ultrasound imaging demonstrated very uniform self-limited growth of Pb-PRL prostate volume that is consistent with the benign, limited cellular proliferation characteristic of BPH and that contrasts with the highly variable, exponential growth of murine prostate cancer models. Castration elicited only a partial reduction in prostate volume, relative to castration-induced regression of the normal prostate gland. The anti-androgen finasteride induced a diminished reduction of Pb-PRL prostate volume versus castration. The limited extent of Pb-PRL mouse prostate volume regression correlated with the initial volume of the stromal compartment, suggesting a differential sensitivity of the epithelial and stromal compartments to androgen withdrawal. Indeed, two-dimensional morphometric analyses revealed a distinctly reduced rate of regression for the stromal compartment in Pb-PRL mice. The myofibroblast component of the Pb-PRL prostate stroma appeared normal, but the stromal compartment contained more fibroblasts and extracellular collagen deposition. Like normal prostate, the rate of regression of the Pb-PRL prostate was partially dependent on TGFß and TNF signaling, but unlike the normal prostate, the extent of castration-induced regression was not affected by TGFß or TNF blockade. Our studies show that androgen deprivation can effectively reduce the overall volume of hyperplastic prostate, but the stromal compartment is relatively resistant, suggesting additional therapies might be required to offer an effective treatment for the clinical manifestations of BPH.</p>","PeriodicalId":7438,"journal":{"name":"American journal of clinical and experimental urology","volume":"11 1","pages":"12-26"},"PeriodicalIF":1.5,"publicationDate":"2023-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10009314/pdf/ajceu0011-0012.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9350858","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: According to the favorable effects of combination therapy to provide better sedation during double-j stent removal and lack of studies investigating the sedative effect of propofol, dexmedetomidine, and midazolam during this procedure. This study aimed to compare the effects of intravenous sedation with propofol, dexmedetomidine and midazolam in double-J ureteral stent removal.
Methods: This double-blinded randomized clinical trial was conducted on 120 patients aged 18-72 who underwent double-J ureteral stent removal in Alzahra hospital, Isfahan, Iran from September to November 2021. Patients were randomly divided into 3 groups. In the first group, propofol was titrated with normal saline and was infused with a loading dose of 0.5 mg/kg and a maintenance dose of 1.5-2.5 mg/kg/h. In the second group, Dexmedetomidine was titrated with normal saline and was infused at a dose of 1 µg/kg within 10 min and then continued at 0.45-0.55 µg/kg. In third group, midazolam was titrated was infused with a loading dose of 0.05 mg/kg and a maintenance dose of 0.05 mg/kg/h. 50 mg of fentanyl was also infused in all the groups. If the patients did not reach the desired sedation level, 10 mg ketamine was infused as a rescue sedative agent for all three groups and repeated if needed in all groups.
Results: The current study was conducted on 120 patients who underwent double-J ureteral stent removal. The comparison of the sedative effect of midazolam, dexmedetomidine, and propofol showed significant differences among the three groups and was higher in the midazolam group (P=0.018). Between the three groups systolic blood pressure and mean arterial pressure was significantly lower in the propofol group (P=0.002). Heart rate was significantly lower in the dexmedetomidine group during both surgery and recovery time (P<0.001). There was no significant difference among the groups during surgery regarding oxygen saturation (P value =0.84). The intergroup comparison indicates that the mean score of surgeon satisfaction is significantly higher in the midazolam group (P-value =0.039).
Conclusion: According to this study midazolam was superior to two other groups and was associated with deeper sedation and higher satisfaction among both patient and surgeon.
{"title":"Comparison of intravenous sedation with propofol, dexmedetomidine and midazolam in double-J ureteral stent removal.","authors":"Hamidreza Shetabi, Faride Akrami Moghaddam, Reza Kazemi","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Background: </strong>According to the favorable effects of combination therapy to provide better sedation during double-j stent removal and lack of studies investigating the sedative effect of propofol, dexmedetomidine, and midazolam during this procedure. This study aimed to compare the effects of intravenous sedation with propofol, dexmedetomidine and midazolam in double-J ureteral stent removal.</p><p><strong>Methods: </strong>This double-blinded randomized clinical trial was conducted on 120 patients aged 18-72 who underwent double-J ureteral stent removal in Alzahra hospital, Isfahan, Iran from September to November 2021. Patients were randomly divided into 3 groups. In the first group, propofol was titrated with normal saline and was infused with a loading dose of 0.5 mg/kg and a maintenance dose of 1.5-2.5 mg/kg/h. In the second group, Dexmedetomidine was titrated with normal saline and was infused at a dose of 1 µg/kg within 10 min and then continued at 0.45-0.55 µg/kg. In third group, midazolam was titrated was infused with a loading dose of 0.05 mg/kg and a maintenance dose of 0.05 mg/kg/h. 50 mg of fentanyl was also infused in all the groups. If the patients did not reach the desired sedation level, 10 mg ketamine was infused as a rescue sedative agent for all three groups and repeated if needed in all groups.</p><p><strong>Results: </strong>The current study was conducted on 120 patients who underwent double-J ureteral stent removal. The comparison of the sedative effect of midazolam, dexmedetomidine, and propofol showed significant differences among the three groups and was higher in the midazolam group (P=0.018). Between the three groups systolic blood pressure and mean arterial pressure was significantly lower in the propofol group (P=0.002). Heart rate was significantly lower in the dexmedetomidine group during both surgery and recovery time (P<0.001). There was no significant difference among the groups during surgery regarding oxygen saturation (<i>P</i> value =0.84). The intergroup comparison indicates that the mean score of surgeon satisfaction is significantly higher in the midazolam group (<i>P</i>-value =0.039).</p><p><strong>Conclusion: </strong>According to this study midazolam was superior to two other groups and was associated with deeper sedation and higher satisfaction among both patient and surgeon.</p>","PeriodicalId":7438,"journal":{"name":"American journal of clinical and experimental urology","volume":"11 2","pages":"160-167"},"PeriodicalIF":1.2,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10165230/pdf/ajceu0011-0160.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9823485","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Carlos Riveros, Mohammed Al-Toubat, Victor Chalfant, Ahmed Elshafei, Allison Feibus, Ana Forero, K C Balaji
Prostate cancer (PCa) is generally considered a disease of older men; however, about 10% of new diagnoses in the US occur in men ≤ 55 years old. Socioeconomic status (SES) has been shown to influence survival in patients with PCa; however, the impact of SES on men with early-onset PCa remains undescribed. Using the National Cancer Database, we identified adult men ≤ 55 years of age with a diagnosis of prostatic adenocarcinoma between 2004-2018. Descriptive statistics were used to characterize differences among different SES groups. Kaplan-Meier (KM) and Cox regression analyses were used to assess the effect of SES on overall survival (OS). A total of 112,563 young patients with PCa with a median follow-up of 79.0 months were identified. Compared to high SES patients, low SES patients were more likely to be African American (42.4% vs. 8.6%; P<0.001), Hispanic (9.5% vs. 2.7%; P<0.001), and uninsured (5.2% vs. 1.1%; P<0.001); they were also more likely to live in a rural area (3.2% vs. 0.1%; P<0.001) and have stage IV disease (5.5% vs. 3.1%; P<0.001). KM analysis showed that a decreasing SES was directly associated with lower rates of OS (log-rank test P<0.001). On multivariable analysis, SES was found to have a negative effect on OS (low SES vs. high SES; hazard ratio [HR] 1.54; 95% confidence interval [CI] 1.41-1.68; P<0.001). In patients with early-onset PCa, SES was associated with lower OS. SES may be considered when implementing programs to improve the management of patients with early-onset PCa.
{"title":"The impact of socioeconomic status on the survival of men with early-onset prostate cancer.","authors":"Carlos Riveros, Mohammed Al-Toubat, Victor Chalfant, Ahmed Elshafei, Allison Feibus, Ana Forero, K C Balaji","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Prostate cancer (PCa) is generally considered a disease of older men; however, about 10% of new diagnoses in the US occur in men ≤ 55 years old. Socioeconomic status (SES) has been shown to influence survival in patients with PCa; however, the impact of SES on men with early-onset PCa remains undescribed. Using the National Cancer Database, we identified adult men ≤ 55 years of age with a diagnosis of prostatic adenocarcinoma between 2004-2018. Descriptive statistics were used to characterize differences among different SES groups. Kaplan-Meier (KM) and Cox regression analyses were used to assess the effect of SES on overall survival (OS). A total of 112,563 young patients with PCa with a median follow-up of 79.0 months were identified. Compared to high SES patients, low SES patients were more likely to be African American (42.4% vs. 8.6%; P<0.001), Hispanic (9.5% vs. 2.7%; P<0.001), and uninsured (5.2% vs. 1.1%; P<0.001); they were also more likely to live in a rural area (3.2% vs. 0.1%; P<0.001) and have stage IV disease (5.5% vs. 3.1%; P<0.001). KM analysis showed that a decreasing SES was directly associated with lower rates of OS (log-rank test P<0.001). On multivariable analysis, SES was found to have a negative effect on OS (low SES vs. high SES; hazard ratio [HR] 1.54; 95% confidence interval [CI] 1.41-1.68; P<0.001). In patients with early-onset PCa, SES was associated with lower OS. SES may be considered when implementing programs to improve the management of patients with early-onset PCa.</p>","PeriodicalId":7438,"journal":{"name":"American journal of clinical and experimental urology","volume":"11 2","pages":"146-154"},"PeriodicalIF":1.2,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10165226/pdf/ajceu0011-0146.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9823487","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Although PSA testing is widely used in prostate cancer diagnosis, it remains an imperfect assay due to its lack of accuracy. While several urine or tissue-based gene expression assays are available to identify patients with higher risk of adverse disease and to aid in deciding treatment options, there is still a critical need for reliable biomarkers to monitor disease progression and treatment response. Autoantibodies (AAbs) produced by the humoral immune response against tumor associated antigens offer an attractive alternative, as they target a wide variety of prostate cancer specific antigens and can be collected by using clinically non-invasive methods. Herein, we review the transition from traditional methods that identify individual AAbs to high throughput approaches that detect multiple targets simultaneously in patient sera. We also discuss how these approaches improved the sensitivity and specificity of AAb detection and enhanced prostate cancer diagnosis and prognosis. Cancer vaccines offer potential as a novel therapeutic strategy in their ability to stimulate both cell-mediated and antibody-mediated cytotoxic responses. Ongoing efforts aim to identify immunotherapy targets that also stimulate a strong antibody response, since antibodies activated by the anti-cancer humoral response can eliminate cancer cells effectively via several distinct mechanisms. Autoantibodies are useful not only for the diagnosis of prostate cancer, predicting disease progression, and tracking response to treatment, but can also be harnessed as therapeutic agents for prostate cancer treatment.
{"title":"Prostate cancer autoantibodies - applications in diagnosis, prognosis, monitoring disease progression and immunotherapy.","authors":"Rahul Jayakrishnan, Cara Schafer, Shyh-Han Tan","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Although PSA testing is widely used in prostate cancer diagnosis, it remains an imperfect assay due to its lack of accuracy. While several urine or tissue-based gene expression assays are available to identify patients with higher risk of adverse disease and to aid in deciding treatment options, there is still a critical need for reliable biomarkers to monitor disease progression and treatment response. Autoantibodies (AAbs) produced by the humoral immune response against tumor associated antigens offer an attractive alternative, as they target a wide variety of prostate cancer specific antigens and can be collected by using clinically non-invasive methods. Herein, we review the transition from traditional methods that identify individual AAbs to high throughput approaches that detect multiple targets simultaneously in patient sera. We also discuss how these approaches improved the sensitivity and specificity of AAb detection and enhanced prostate cancer diagnosis and prognosis. Cancer vaccines offer potential as a novel therapeutic strategy in their ability to stimulate both cell-mediated and antibody-mediated cytotoxic responses. Ongoing efforts aim to identify immunotherapy targets that also stimulate a strong antibody response, since antibodies activated by the anti-cancer humoral response can eliminate cancer cells effectively via several distinct mechanisms. Autoantibodies are useful not only for the diagnosis of prostate cancer, predicting disease progression, and tracking response to treatment, but can also be harnessed as therapeutic agents for prostate cancer treatment.</p>","PeriodicalId":7438,"journal":{"name":"American journal of clinical and experimental urology","volume":"11 2","pages":"79-102"},"PeriodicalIF":1.2,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10165224/pdf/ajceu0011-0079.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9823488","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The fibroepithelial stromal polyp is a benign polypoid proliferation of the stroma with overlying epithelium. Because the lesion contains atypical stromal cells, sometimes it can be overdiagnosed as sarcoma or with myxoid stroma, it can be misdiagnosed as angiomyxoma. The reported locations are mainly in the lower female genital tract, urethra, and rarely extragenital sites, such as the breast, and are exceptionally rare in the bladder. We encountered a 65-year-old man who presented with two small velvety, erythematous patches on the posterior bladder wall. The final diagnosis is a fibroepithelial stromal polyp of the bladder. Familiarity with this lesion will prevent overinterpretation of this benign lesion as a malignancy.
{"title":"Fibroepithelial stromal polyp of bladder-a mimicker of sarcoma or angiomyxoma at uncommon location.","authors":"Liping Li, Robert E Weiss, Debra Heller","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The fibroepithelial stromal polyp is a benign polypoid proliferation of the stroma with overlying epithelium. Because the lesion contains atypical stromal cells, sometimes it can be overdiagnosed as sarcoma or with myxoid stroma, it can be misdiagnosed as angiomyxoma. The reported locations are mainly in the lower female genital tract, urethra, and rarely extragenital sites, such as the breast, and are exceptionally rare in the bladder. We encountered a 65-year-old man who presented with two small velvety, erythematous patches on the posterior bladder wall. The final diagnosis is a fibroepithelial stromal polyp of the bladder. Familiarity with this lesion will prevent overinterpretation of this benign lesion as a malignancy.</p>","PeriodicalId":7438,"journal":{"name":"American journal of clinical and experimental urology","volume":"11 4","pages":"348-351"},"PeriodicalIF":1.2,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10461029/pdf/ajceu0011-0348.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10118302","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mehdi Dadpour, Amir Mohammad Soltani, Mahyar Ghafoori, Abbas Basiri, Nasrin Borumandnia, Amirhossein Nayebzade, Behzad Narouie, Hamed Hasani, Nasser Shakhssalim
Introduction: To evaluate and compare the rate of cancer detection by two methods Saturated TRUS guided biopsy and ultrasound/magnetic resonance imaging (US/MRI)-targeted biopsy in patients with primary negative prostate cancer in standard 12 cores biopsy evaluation but still have elevated prostate specific antigen (PSA).
Materials and methods: From 105 patients who met our inclusion criteria, 53 patients underwent US/MRI-targeted biopsy and 52 remaining patients underwent Saturated 20 core TRUS guided biopsy in a prospective randomized clinical trial.
Results: The mean age (±SD) was 62.2 (±8.2) year. The mean PSA (±SD) was 11.8 (±7.5) ng/ml. The mean prostate volume was 56.1 (±24.8) ml. Adenocarcinoma of prostate was detected in 9/52 (17.3%) patients in groups saturated biopsy and 14/53 (26.4%) patients in US/MRI-targeted biopsy group and there was no difference in cancer detection rate between 2 groups (P=0.252). except four patients with fever (two in each group), there was no other serious complication (Clavien grade 3 or higher) occurred in the patients. In the multivariate analysis, higher pre-procedure PSA, lower size of the prostate, pathology of ASAP and presence of nodule in DRE were independent predictors for cancer detection in second biopsy (P=0.036, P<0.001, P=0.013 and P=0.031, respectively).
Conclusion: We didn't find any superiority in cancer detection rate and any different in complication rate between these two methods saturated TRUS guided biopsy and US/MRI-targeted biopsy.
{"title":"Ultrasound/MRI-targeted biopsy versus saturated trans-rectal ultrasound guided biopsy of prostate in patients with primary negative conventional biopsy and still elevated PSA: a prospective randomized clinical trial.","authors":"Mehdi Dadpour, Amir Mohammad Soltani, Mahyar Ghafoori, Abbas Basiri, Nasrin Borumandnia, Amirhossein Nayebzade, Behzad Narouie, Hamed Hasani, Nasser Shakhssalim","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Introduction: </strong>To evaluate and compare the rate of cancer detection by two methods Saturated TRUS guided biopsy and ultrasound/magnetic resonance imaging (US/MRI)-targeted biopsy in patients with primary negative prostate cancer in standard 12 cores biopsy evaluation but still have elevated prostate specific antigen (PSA).</p><p><strong>Materials and methods: </strong>From 105 patients who met our inclusion criteria, 53 patients underwent US/MRI-targeted biopsy and 52 remaining patients underwent Saturated 20 core TRUS guided biopsy in a prospective randomized clinical trial.</p><p><strong>Results: </strong>The mean age (±SD) was 62.2 (±8.2) year. The mean PSA (±SD) was 11.8 (±7.5) ng/ml. The mean prostate volume was 56.1 (±24.8) ml. Adenocarcinoma of prostate was detected in 9/52 (17.3%) patients in groups saturated biopsy and 14/53 (26.4%) patients in US/MRI-targeted biopsy group and there was no difference in cancer detection rate between 2 groups (P=0.252). except four patients with fever (two in each group), there was no other serious complication (Clavien grade 3 or higher) occurred in the patients. In the multivariate analysis, higher pre-procedure PSA, lower size of the prostate, pathology of ASAP and presence of nodule in DRE were independent predictors for cancer detection in second biopsy (P=0.036, P<0.001, P=0.013 and P=0.031, respectively).</p><p><strong>Conclusion: </strong>We didn't find any superiority in cancer detection rate and any different in complication rate between these two methods saturated TRUS guided biopsy and US/MRI-targeted biopsy.</p>","PeriodicalId":7438,"journal":{"name":"American journal of clinical and experimental urology","volume":"11 4","pages":"312-319"},"PeriodicalIF":1.2,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10461031/pdf/ajceu0011-0312.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10176404","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Hannah Ruetten, Simran K Sandhu, Olivia Fox, Jonathan Zhu, Jaskiran K Sandhu, Chad M Vezina
Prostatic inflammation and prostatic fibrosis are associated with lower urinary tract dysfunction in men. Prostatic inflammation arising from a transurethral uropathogenic E. coli infection is sufficient to increase prostatic collagen content in male mice. It is not known whether and how the sequence, duration and chronology of prostatic infection influence urinary function, prostatic inflammation and collagen content. We placed a transurethral catheter into adult male C57BL/6J mice to deliver uropathogenic E. coli UTI189 two-weeks prior to study endpoint (to evaluate the short-term impact of infection), 10-weeks prior to study endpoint (to evaluate the long-term impact of infection), or two-, six-, and ten-weeks prior to endpoint (to evaluate the impact of repeated intermittent infection). Mice were catheterized the same number of times across all experimental groups and instilled with sterile saline when not instilled with E. coli to control for the variable of catheterization. We measured bacterial load in free catch urine, body weight and weight of bladder and dorsal prostate; prostatic density of leukocytes, collagen and procollagen 1A1 producing cells, and urinary function. Transurethral E. coli instillation caused more severe and persistent bacteriuria in mice with a history of one or more transurethral instillations of sterile saline or E. coli. Repeated intermittent infections resulted in a greater relative bladder wet weight than single infections. However, voiding function, as measured by the void spot assay, and the density of collagen and ProCOL1A1+ cells in dorsal prostate tissue sections did not significantly differ among infection groups. The density of CD45+ leukocytes was greater in the dorsal prostate of mice infected two weeks prior to study endpoint but not in other infection groups compared to uninfected controls.
{"title":"The impact of short term, long term and intermittent <i>E. coli</i> infection on male C57BL/6J mouse prostate histology and urinary physiology.","authors":"Hannah Ruetten, Simran K Sandhu, Olivia Fox, Jonathan Zhu, Jaskiran K Sandhu, Chad M Vezina","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Prostatic inflammation and prostatic fibrosis are associated with lower urinary tract dysfunction in men. Prostatic inflammation arising from a transurethral uropathogenic <i>E. coli</i> infection is sufficient to increase prostatic collagen content in male mice. It is not known whether and how the sequence, duration and chronology of prostatic infection influence urinary function, prostatic inflammation and collagen content. We placed a transurethral catheter into adult male C57BL/6J mice to deliver uropathogenic <i>E. coli</i> UTI189 two-weeks prior to study endpoint (to evaluate the short-term impact of infection), 10-weeks prior to study endpoint (to evaluate the long-term impact of infection), or two-, six-, and ten-weeks prior to endpoint (to evaluate the impact of repeated intermittent infection). Mice were catheterized the same number of times across all experimental groups and instilled with sterile saline when not instilled with <i>E. coli</i> to control for the variable of catheterization. We measured bacterial load in free catch urine, body weight and weight of bladder and dorsal prostate; prostatic density of leukocytes, collagen and procollagen 1A1 producing cells, and urinary function. Transurethral <i>E. coli</i> instillation caused more severe and persistent bacteriuria in mice with a history of one or more transurethral instillations of sterile saline or <i>E. coli</i>. Repeated intermittent infections resulted in a greater relative bladder wet weight than single infections. However, voiding function, as measured by the void spot assay, and the density of collagen and ProCOL1A1+ cells in dorsal prostate tissue sections did not significantly differ among infection groups. The density of CD45+ leukocytes was greater in the dorsal prostate of mice infected two weeks prior to study endpoint but not in other infection groups compared to uninfected controls.</p>","PeriodicalId":7438,"journal":{"name":"American journal of clinical and experimental urology","volume":"11 1","pages":"59-68"},"PeriodicalIF":1.2,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10009312/pdf/ajceu0011-0059.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9497826","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Alfonso H Santos, Amer Belal, Sherif Badra, Hisham Ibrahim, Kawther Alquadan, Rohan Mehta, Muhannad A Leghrouz
Objective: Our objective was to identify consistent predictors of multiple adverse outcomes of adult deceased donor (DD) kidney transplant recipients (KTRs) of varying sensitization status.
Methods: We used the national transplant database in studying 62037 adult DD-KTRs between Dec. 2007 and Jun. 2015 stratified into sensitization cohorts based on calculated panel reactive antibody (CPRA) of <10%, 10%-79%, and ≥80%. We used multivariable logistic regressions for the analysis of risks for delayed graft function (DGF), and of acute rejection (AR) and hospitalization in the first year of transplant, and Cox hazard regression for 5-year overall graft loss (OAGL) and death.
Results: The kidney donor risk index (KDRI) highest two quartiles ≥1.45 and 1.15-1.44 were the most consistent predictors for 100% of adverse outcomes (OAGL, death, DGF, AR, and hospitalization) with high significance (P<0.0001) across all sensitization cohorts. The two risk factors that were consistently associated with 80% of adverse outcomes across sensitization cohorts were: (1) pre-transplant dialysis duration >2 years was significantly associated with increased risks of overall graft loss, death, DGF, and hospitalization; and (2) Black KTR race was significantly associated with increased risks of DGF, AR, and hospitalization, and decreased risk of death. Diabetes and KTR age >65 (years) were significant risk factors for overall loss and death across sensitization cohorts.
Conclusions: The two highest KDRI quartiles, pre-transplant dialysis duration >2 years, and African American recipient race are consistent predictors of multiple adverse outcomes in adult DDKTRs across sensitization strata and should be among the factors considered in clinical decision-making and research models in kidney transplantation.
{"title":"Common predictors of adverse outcomes in adult deceased donor kidney transplant recipients with varying sensitization.","authors":"Alfonso H Santos, Amer Belal, Sherif Badra, Hisham Ibrahim, Kawther Alquadan, Rohan Mehta, Muhannad A Leghrouz","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Objective: </strong>Our objective was to identify consistent predictors of multiple adverse outcomes of adult deceased donor (DD) kidney transplant recipients (KTRs) of varying sensitization status.</p><p><strong>Methods: </strong>We used the national transplant database in studying 62037 adult DD-KTRs between Dec. 2007 and Jun. 2015 stratified into sensitization cohorts based on calculated panel reactive antibody (CPRA) of <10%, 10%-79%, and ≥80%. We used multivariable logistic regressions for the analysis of risks for delayed graft function (DGF), and of acute rejection (AR) and hospitalization in the first year of transplant, and Cox hazard regression for 5-year overall graft loss (OAGL) and death.</p><p><strong>Results: </strong>The kidney donor risk index (KDRI) highest two quartiles ≥1.45 and 1.15-1.44 were the most consistent predictors for 100% of adverse outcomes (OAGL, death, DGF, AR, and hospitalization) with high significance (P<0.0001) across all sensitization cohorts. The two risk factors that were consistently associated with 80% of adverse outcomes across sensitization cohorts were: (1) pre-transplant dialysis duration >2 years was significantly associated with increased risks of overall graft loss, death, DGF, and hospitalization; and (2) Black KTR race was significantly associated with increased risks of DGF, AR, and hospitalization, and decreased risk of death. Diabetes and KTR age >65 (years) were significant risk factors for overall loss and death across sensitization cohorts.</p><p><strong>Conclusions: </strong>The two highest KDRI quartiles, pre-transplant dialysis duration >2 years, and African American recipient race are consistent predictors of multiple adverse outcomes in adult DDKTRs across sensitization strata and should be among the factors considered in clinical decision-making and research models in kidney transplantation.</p>","PeriodicalId":7438,"journal":{"name":"American journal of clinical and experimental urology","volume":"11 3","pages":"235-248"},"PeriodicalIF":1.2,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10333136/pdf/ajceu0011-0235.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9872401","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}