Publications by authors named "Puneet Sindhwani"

27 Publications

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Fluorescence-Based Ratiometric Analysis of Sperm Centrioles (FRAC) Finds Patient Age and Sperm Morphology Are Associated With Centriole Quality.

Front Cell Dev Biol 2021 22;9:658891. Epub 2021 Apr 22.

Department of Biological Sciences, College of Natural Sciences and Mathematics, University of Toledo, Toledo, OH, United States.

A large proportion of infertility and miscarriage causes are unknown. One potential cause is a defective sperm centriole, a subcellular structure essential for sperm motility and embryonic development. Yet, the extent to which centriolar maladies contribute to male infertility is unknown due to the lack of a convenient way to assess centriole quality. We developed a robust, location-based, ratiometric assay to overcome this roadblock, the Fluorescence-based Ratiometric Assessment of Centrioles (FRAC). We performed a case series study with semen samples from 33 patients, separated using differential gradient centrifugation into higher-grade (pellet) and lower-grade (interface) sperm fractions. Using a reference population of higher-grade sperm from infertile men with morphologically standard sperm, we found that 79% of higher-grade sperm of infertile men with substandard sperm morphology have suboptimal centrioles ( = 0.0005). Moreover, tubulin labeling of the sperm distal centriole correlates negatively with age ( = 0.004, = -0.66). These findings suggest that FRAC is a sensitive method and that patient age and sperm morphology are associated with centriole quality.
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http://dx.doi.org/10.3389/fcell.2021.658891DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8100587PMC
April 2021

Risk factors for delayed graft function and their impact on graft outcomes in live donor kidney transplantation.

Int Urol Nephrol 2021 Mar 4;53(3):439-446. Epub 2021 Jan 4.

Department of Urology and Renal Transplant, University of Toledo, 3000, Arlington Ave, MS1091, Toledo, OH, 43614, USA.

Background: Delayed graft function (DGF) is a manifestation of acute kidney injury uniquely framed within the transplant process and a predictor of poor long-term graft function1. It is less common in the setting of living donor (LD) kidney transplantation. However, the detrimental impact of DGF on graft survival is more pronounced in LD2.

Purpose: To study the effects of DGF in the setting of LD kidney transplantation.

Methods: We performed a retrospective analysis of LD kidney transplantations performed between 2010 and 2018 in the UNOS/OPTN database for DGF and its effect on graft survival.

Results: A total of 42,736 LD recipients were identified, of whom 1115 (2.6%) developed DGF. Recipient dialysis status, male gender, diabetes, end-stage renal disease, donor age, right donor nephrectomy, panel reactive antibodies, HLA mismatch, and cold ischemia time were independent predictors of DGF. Three-year graft survival in patients with and without DGF was 89% and 95%, respectively. DGF was the greatest predictor of graft failure at three years (hazard ratio = 1.766, 95% CI: 1.514-2.059, P = 0.001) and was associated with higher rates of rejection (9% vs. 6.28%, P = 0.0003). Among patients with DGF, the graft survival rates with and without rejection were not different.

Conclusion: DGF is a major determinant of poor graft functional outcomes, independent of rejection.
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http://dx.doi.org/10.1007/s11255-020-02687-5DOI Listing
March 2021

Lack of trusted diagnostic tools for undetermined male infertility.

J Assist Reprod Genet 2021 Feb 2;38(2):265-276. Epub 2021 Jan 2.

Department of Biological Sciences, College of Medicine and Life Sciences, University of Toledo, Toledo, OH, 43607, USA.

Semen analysis is the cornerstone of evaluating male infertility, but it is imperfect and insufficient to diagnose male infertility. As a result, about 20% of infertile males have undetermined infertility, a term encompassing male infertility with an unknown underlying cause. Undetermined male infertility includes two categories: (i) idiopathic male infertility-infertile males with abnormal semen analyses with an unknown cause for that abnormality and (ii) unexplained male infertility-males with "normal" semen analyses who are unable to impregnate due to unknown causes. The treatment of males with undetermined infertility is limited due to a lack of understanding the frequency of general sperm defects (e.g., number, motility, shape, viability). Furthermore, there is a lack of trusted, quantitative, and predictive diagnostic tests that look inside the sperm to quantify defects such as DNA damage, RNA abnormalities, centriole dysfunction, or reactive oxygen species to discover the underlying cause. To better treat undetermined male infertility, further research is needed on the frequency of sperm defects and reliable diagnostic tools that assess intracellular sperm components must be developed. The purpose of this review is to uniquely create a paradigm of thought regarding categories of male infertility based on intracellular and extracellular features of semen and sperm, explore the prevalence of the various categories of male factor infertility, call attention to the lack of standardization and universal application of advanced sperm testing techniques beyond semen analysis, and clarify the limitations of standard semen analysis. We also call attention to the variability in definitions and consider the benefits towards undetermined male infertility if these gaps in research are filled.
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http://dx.doi.org/10.1007/s10815-020-02037-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7884538PMC
February 2021

An improbable trifecta: Occurrence of xanthogranulomatous prostatitis, prostate cancer, and prostatic abscess in a single patient.

Urol Case Rep 2021 Mar 7;35:101526. Epub 2020 Dec 7.

The Toledo Clinic, Toledo, OH, USA.

Xanthogranulomatous prostatitis (XGP) is a rare disease that can mimic the clinical and imaging findings of prostate cancer. Differentiation of these diseases is vital in order to offer the correct treatment. Histological examination of prostate tissue is the definitive manner in which XGP is distinguished from prostate cancer. This case demonstrates the rare possibility of concurrent findings of prostate abscess, prostate cancer, and XGP, further clouding diagnostic assessment. Percutaneous aspiration and antibiotic treatment of the abscess reduced lower urinary tract symptoms and eliminated XGP on subsequent prostate biopsy. Careful work up is necessary to prevent unnecessary interventions or missed diagnoses.
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http://dx.doi.org/10.1016/j.eucr.2020.101526DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7732860PMC
March 2021

Plasmacytoid variant of urothelial carcinoma of the bladder manifesting as bilateral ureteral and small bowel obstruction.

Urol Case Rep 2020 Nov 16;33:101415. Epub 2020 Sep 16.

The University of Toledo College of Medicine and Life Sciences, Toledo, OH, USA.

Plasmacytoid urothelial carcinoma (PUC) is a rare variant of bladder cancer characterized by distinct histopathology and advanced stage at diagnosis. Multimodal treatment is usually indicated. We present a case of PUC causing bilateral ureteral obstruction with subsequent renal failure followed shortly by malignant small bowel obstruction, demonstrating the need for a high degree of clinical suspicion in diagnosis of this aggressive subtype. Moreover, the local invasiveness of the disease cannot be understated, given that it can rapidly spread with little radiologic evidence of progression until it is at an advanced stage.
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http://dx.doi.org/10.1016/j.eucr.2020.101415DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7574283PMC
November 2020

Robotic-assisted Donor Nephrectomy: As Safe as Laparoscopic Donor Nephrectomy.

Surg Technol Int 2020 Nov;37:171-174

University of Toledo Medical Center, Department of Urology and Renal Transplantation Toledo, OH, USA.

Objectives: Robotic-assisted donor nephrectomy has become increasingly popular in recent years. We sought to compare robotic-assisted outcomes to operative outcomes in a historical cohort of laparoscopic donor nephrectomies.

Materials And Methods: A retrospective review of 58 consecutive donor nephrectomies at a single center by two surgeons from 2015 to 2019 was performed.

Results: Robotic-assisted (n = 32) and laparoscopic (n =26) donors were comparable in terms of estimated blood loss (66.4 vs. 62.5 mL; p=0.81) and length of stay (1.6 vs. 1.5 days; p=0.37). The post-operative change in creatinine was not significantly different between the groups (-0.45 vs. -0.45; p=0.97). Warm ischemia time was longer in the robotic group (7.36 vs. 5.15 minutes; p < 0.01). Case duration was significantly longer for robotic-assisted cases (306 vs. 247 minutes; p < 0.01). However, robotic cases were more likely to be right-sided (6/32 (18.8%) vs. 1/26 (3.8%)) and have vascular multiplicity (7/32 (21.9%) vs. 0/26 (0%)). There was one Clavien II or greater complication in the robotic group, and none in the laparoscopic group.

Conclusions: Our data agree with previous reports that robotic-assisted donor nephrectomy is safe and has similar outcomes to a laparoscopic approach. Moreover, cases with multiple renal arteries or veins and right-sided cases were completed safely using the robotic approach. The longer case duration in the robotic group was attributed to the learning curve associated with implementing a new technique, and later robotic operative times approached laparoscopic operative times.
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November 2020

Role of Synthetic Mesh Renorrhaphy and Neocapsule Reconstruction to Salvage Posttransplant Severely Damaged Renal Allografts.

Exp Clin Transplant 2021 Jan 4;19(1):32-37. Epub 2020 Mar 4.

From the Department of Urology, The University of Toledo, Toledo, Ohio, USA.

Objectives: As the recipient pool continues to rise, it is vital to conserve donor organs whenever possible. Injured renal allografts continue to be discarded for a variety of reasons, and salvaging potentially useable grafts is of utmost importance. Little information is available on outcomes of salvaged allografts. Here, we present an easily replicable technique to salvage damaged renal allografts using polyglactin mesh.

Materials And Methods: Polyglactin woven mesh was used to salvage 4 otherwise irreparably injured allografts. In the first case, unidentified extracorporeal shockwave lithotripsy-induced microfractures 2 months before procurement of a deceased-donor kidney led to significant capsular injury. In the second case, rapid recovery of a deceased-donor kidney limited evaluation, and severe capsular rupture was diagnosed after perfusion. In the third case, an anticoagulated pediatric recipient received a living related-donor kidney from his mother, and a biopsy-induced hematoma 2 months posttransplant led to severe capsular denudation. In the fourth case, a pumped kidney from a donor after cardiac death developed severe focal capsular denudation. In each case, a keyhole hilar-sparing incision was made in an industry-standard 12 × 12-inch polyglactin mesh sheet, which was then fitted and sutured in a vest-over-pants method to provide a scaffold for hemostasis and capsular healing. Topical hemostatic agents were added in the first and fourth cases. Patients were followed longitudinally.

Results: All allografts were successfully salvaged using our technique, and none developed Page kidney, hydronephrosis, urinoma, or hemorrhage. At last follow-up, recipient 1 had kidney loss 7 years postrepair secondary to chronic allograft nephropathy, recipient 2 was lost to follow-up at 1 year with normal renal function, and recipients 3 and 4 had normal renal function at years 3 and 7 posttransplant.

Conclusions: This simple technique using readily available materials can salvage allografts that would have been potentially explanted or discarded.
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http://dx.doi.org/10.6002/ect.2019.0308DOI Listing
January 2021

EDITORIAL COMMENT.

Authors:
Puneet Sindhwani

Urology 2020 02;136:150-151

Department of Urology, Renal Transplantation and Donation Sciences, University of Toledo College of Medicine and Life Sciences, Toledo OH 43614. Electronic address:

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http://dx.doi.org/10.1016/j.urology.2019.10.035DOI Listing
February 2020

The Role of Sperm Centrioles in Human Reproduction - The Known and the Unknown.

Front Cell Dev Biol 2019 1;7:188. Epub 2019 Oct 1.

Department of Biological Sciences, College of Natural Sciences and Mathematics, The University of Toledo, Toledo, OH, United States.

Each human spermatozoon contains two remodeled centrioles that it contributes to the zygote. There, the centrioles reconstitute a centrosome that assembles the sperm aster and participate in pronuclei migration and cleavage. Thus, centriole abnormalities may be a cause of male factor infertility and failure to carry pregnancy to term. However, the precise mechanisms by which sperm centrioles contribute to embryonic development in humans are still unclear, making the search for a link between centriole abnormalities and impaired male fecundity particularly difficult. Most previous investigations into the role of mammalian centrioles during fertilization have been completed in murine models; however, because mouse sperm and zygotes appear to lack centrioles, these studies provide information that is limited in its applicability to humans. Here, we review studies that examine the role of the sperm centrioles in the early embryo, with particular emphasis on humans. Available literature includes case studies and case-control studies, with a few retrospective studies and no prospective studies reported. This literature has provided some insight into the morphological characteristics of sperm centrioles in the zygote and has allowed identification of some centriole abnormalities in rare cases. Many of these studies suggest centriole involvement in early embryogenesis based on phenotypes of the embryo with only indirect evidence for centriole abnormality. Overall, these studies suggest that centriole abnormalities are present in some cases of sperm with asthenoteratozoospermia and unexplained infertility. Yet, most previously published studies have been restricted by the laborious techniques (like electron microscopy) and the limited availability of centriolar markers, resulting in small-scale studies and the lack of solid causational evidence. With recent progress in sperm centriole biology, such as the identification of the unique composition of sperm centrioles and the discovery of the atypical centriole, it is now possible to begin to fill the gaps in sperm centriole epidemiology and to identify the etiology of sperm centriole dysfunction in humans.
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http://dx.doi.org/10.3389/fcell.2019.00188DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6781795PMC
October 2019

Neoadjuvant chemotherapy for high-risk prostatic adenocarcinoma.

IJU Case Rep 2019 Mar 28;2(2):61-64. Epub 2019 Jan 28.

Department of Urology College of Medicine and Life Sciences The University of Toledo Toledo Ohio USA.

Introduction: Neoadjuvant chemotherapy in high-risk, locally advanced prostate cancer remains an understudied area of prostate cancer. Chemotherapy continues to be a viable option. The combination with surgery may be desired but lacks data for complete recommendation.

Case Presentation: We demonstrate the successful utilization of chemotherapy in the neoadjuvant arena. A 70-year-old male was diagnosed with high-risk prostate cancer on biopsy. Upon multiparametric magnetic resonance imaging, the patient had local rectal wall invasion and stage T4 N0 M0 after a negative bone scan. After treatment with androgen-deprivation therapy and docetaxel, repeat multiparametric magnetic resonance imaging showed regression of rectal invasion. The patient elected for prostatectomy and avoided proctectomy and colostomy. The patient's postoperative prostate-specific antigen was undetectable on initial follow-up.

Conclusion: We show that neoadjuvant chemotherapy merits further study and may provide a more permanent surgical option for patients.
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http://dx.doi.org/10.1002/iju5.12031DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7292178PMC
March 2019

Review of Guidelines for the Evaluation and Treatment of Leukocytospermia in Male Infertility.

World J Mens Health 2019 May 31;37(2):128-137. Epub 2018 Dec 31.

Department of Urology, College of Medicine and Life Sciences, University of Toledo, Toledo, OH, USA.

Leukocytospermia is an ill-defined and poorly understood condition affecting up to 30% of male factor infertility. Current guidelines on leukocytospermia vary significantly, although it has been linked to increased rates of infertility, uncertainty about its clinical significance, diagnosis, and treatment remains. The guidelines are conflicting with sparse data scattered across different specialties and continents. This study aims to compare and contrast available international guidelines and recommendations. In addition to these guidelines, we sought to consolidate the findings of trials over the last several decades. English language articles on human observational studies, retrospective, prospective, clinical trials and randomized control trials were searched for using the following terms: "leukocytospermia, pyospermia, and male infertility." Articles about treatment and management of leukocytospermia that were published between January 2010 and April 2018 were included, as well as four articles referenced in best practice and guideline statements from urological and andrological associations. Disagreements on this topic are highlighted as some guidelines describe no correlation between leukocytospermia and infertility while others show that treatment leads to improvement of sperm quality by many measures including improved pregnancy rate. Various treatments have been suggested including antibiotics, anti-inflammatory medications, and frequent ejaculation. There is a need for definitive characterization of Leukocytospermia as an infectious or inflammatory marker and a re-evaluation of the leukocyte concentration threshold. Additional studies investigating rates of conception as a measure of outcome are needed, to provide greater level of evidence and generalizability of leukocytopsermia management.
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http://dx.doi.org/10.5534/wjmh.180078DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6479086PMC
May 2019

Initial Experience with the Use of a Robotic Stapler for Robot-Assisted Donor Nephrectomy.

J Endourol 2018 11 3;32(11):1054-1057. Epub 2018 Oct 3.

Department of Urology, University of Toledo College of Medicine and Life Sciences , Toledo, Ohio.

Introduction: Since the first description of robot-assisted laparoscopic donor nephrectomy for living donor renal transplantation, additional studies have noted outcomes comparable to traditional laparoscopic surgery. Urologists have embraced the technical advantages of the robotic approach, including improved dissection and more accurate graft preservation. With the advent of robotic stapling, we aim to demonstrate the feasibility of the use of robotic stapling for living-donor nephrectomies.

Materials And Methods: Ten cases of da Vinci EndoWrist Stapler use during robot-assisted donor nephrectomy by a single surgeon are reported. Variables examined included patient anatomy, estimated blood loss (EBL), warm ischemia time (WIT), postoperative complications, and graft function at follow-up. The costs of the laparoscopic and robotic staplers at our institution are reported.

Results: One right and nine left nephrectomies were performed by a single surgeon. Eight living donors had a single renal artery and vein, while two had multiple renal arteries and renal veins. A single vascular stapler load (45-mm, white cartridge) was used for vessels in all cases. WIT was <6 minutes in each case, and EBL ranged from 13 to 100 mL. Sufficient length on the renal artery and vein was obtained to execute anastomoses in all cases. Only one patient had postoperative complications that were related to anesthesia. Graft function of recipients and postoperative renal function has been adequate to date. The cost of using the robotic stapler was $705 (EndoWrist Stapler), and the cost of the laparoscopic stapler (Endo GIA™ Stapler; Medtronic, Dublin, Ireland) was $494.06.

Conclusions: The use of robotic stapler is feasible in terms of patient safety, technique, postoperative outcomes, and cost in both left- and right-sided living-donor robotic nephrectomies. Further research is needed to confirm the benefit and safety of EndoWrist stapler use in robotic donor nephrectomies compared to laparoscopic stapler use.
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http://dx.doi.org/10.1089/end.2018.0461DOI Listing
November 2018

Comparison of guideline recommendations for antimicrobial prophylaxis in urologic procedures: variability, lack of consensus, and contradictions.

Int Urol Nephrol 2018 Nov 25;50(11):1923-1937. Epub 2018 Aug 25.

Department of Urology, University of Toledo College of Medicine and Life Sciences, 3000 Arlington Avenue, Toledo, OH, 43614, USA.

Purpose: This review assesses guideline discrepancies for urologic surgery antimicrobial prophylaxis and identifies opportunities for improvement of antimicrobial prophylaxis and stewardship.

Methods: Literature search using PubMed, Embase, Cochrane, and association websites identified guidelines for review from the American Urological Association, Canadian Urological Association, European Association of Urology, Japanese Urological Association, and Association of Health-System Pharmacists/Infectious Disease Society of America/Surgical Infection Society/Society for Healthcare Epidemiology of America.

Results: The greatest variability between guidelines was found in prophylaxis recommendations for prostate brachytherapy, transurethral resection of bladder tumor, extracorporeal shock wave lithotripsy (ESWL), and ureteroscopy with manipulation. Variability was also present in recommended duration of prophylaxis and recommended antibiotic. Contradictions between guidelines existed regarding prophylaxis for patients with indwelling stents undergoing ESWL, as well as for patients at risk of endocarditis undergoing urologic procedures. Procedures with the least variability in prophylaxis recommendation included diagnostic procedures (cystourethroscopy, urodynamic studies, and diagnostic ureteroscopy), transurethral resection of prostate, transrectal prostate biopsy, percutaneous nephrolithotomy, procedures involving prosthesis placement or intestine, and open or laparoscopic procedures.

Conclusions: Consensus recommendations are present for several procedures, many of which still rely on non-urologic data. Several other procedures have variability in recommendations, generally due to a lack of strong data. The use of risk factors as indication for prophylaxis in many procedures is at times ambiguous and confusing. Together, these observations indicate a need for further research to provide more robust and consistent guidelines for antimicrobial prophylaxis and stewardship in the field of urology.
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http://dx.doi.org/10.1007/s11255-018-1971-1DOI Listing
November 2018

Complete Chain of the First Global Kidney Exchange Transplant and 3-yr Follow-up.

Eur Urol Focus 2018 03 23;4(2):190-197. Epub 2018 Aug 23.

University of Toledo Medical Center, Toledo, OH, USA; Alliance for Paired Donation, Perrysburg, OH, USA. Electronic address:

Background: Global Kidney Exchange (GKE) offers an opportunity to expand living renal transplantation internationally to patients without financial means. These international pairs are entered into a US kidney exchange program that provides long-term financial support in an effort to identify opportunities for suitable exchanges for both these international pairs and US citizens.

Objective: While the promise of GKE is significant, it has been met with ethical criticism since its inception in 2015. This paper aims to demonstrate the selection process and provide >3 yr of follow-up on the first GKE donor and recipient from the Philippines.

Design, Setting, And Participants: The first GKE transplant occurred with a young Filipino husband and wife who were immunologically compatible, but lacked the financial means to continue hemodialysis or undergo a kidney transplant in their home country. The pair was enrolled in the Alliance for Paired Donation matching system, several alternative kidney exchanges were identified, and the pair subsequently underwent renal transplantation and donation in the USA financed by philanthropy. The resulting nonsimultaneous extended altruistic chain provided transplantation for the Filipino husband and 11 US patients.

Outcome Measurements And Statistical Analysis: The Filipino donor and recipient were followed by transplant professionals in both the Philippines and the USA. Follow-up data were maintained as required by the Organ Procurement and Transplantation Network in the USA.

Results And Limitations: The Filipino donor has normal blood pressure and renal function, and the Filipino recipient is doing well 3.5 yr after their donation and transplantation.

Conclusions: While criticisms of GKE highlight concerns for possible exploitation of financially disadvantaged groups, these results demonstrate that these concerns did not come to fruition, and the outcome experienced by the GKE donor and recipient (and other US participants) was successful.

Patient Summary: The first Filipino Global Kidney Exchange (GKE) donor-recipient pair continues to be followed by both US and Filipino transplant centers. Both are in good health, support the GKE program, and advocate for its expansion.
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http://dx.doi.org/10.1016/j.euf.2018.07.021DOI Listing
March 2018

Can components of the plasminogen activation system predict the outcome of kidney transplants?

Cent Eur J Immunol 2018 30;43(2):222-230. Epub 2018 Jun 30.

Urology Department, The University of Toledo, Toledo, United States of America.

Proteolytic and antiproteolytic enzymes play a critical role in the physiology and pathology of different stages of human life. One of the important members of the proteolytic family is the plasminogen activation system (PAS), which includes several elements crucial for this review: the 50 kDa glycoprotein plasminogen activator inhibitor 1 (PAI-1) that inhibits tissue-type (tPA) and urokinase-type plasminogen activator (uPA). These two convert plasminogen into its active form named plasmin that can lyse a broad spectrum of proteins. Urokinase receptor (uPAR) is the binding site of uPA. This glycoprotein on the cell surface facilitates urokinase activation of plasminogen, creating high proteolytic activity close to the cell surface. PAS activities have been reported to predict the outcome of kidney transplants. However, reports on expression of PAS in kidney transplants seem to be controversial. On the one hand there are reports that impaired proteolytic activity leads to induction of chronic allograft nephropathy, while on the other hand treatment with uPA and tPA can restore function of acute renal transplants. In this comprehensive review we describe the complexity of the PAS as well as biological effects of the PAS on renal allografts, and provide a possible explanation of the reported controversy.
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http://dx.doi.org/10.5114/ceji.2018.77394DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6102612PMC
June 2018

Ciprofloxacin-Resistant Bacteria on Pre-Prostate Biopsy Rectal Swab Culture: A Northwest Ohio Study.

Surg Infect (Larchmt) 2018 Aug/Sep;19(6):614-617. Epub 2018 Aug 21.

1 Department of Urology, College of Medicine and Life Sciences, The University of Toledo, Toledo, Ohio.

Background: Ciprofloxacin is given to patients routinely prior to trans-rectal prostate biopsy. However bacterial resistance to this antibiotic has increased nationally resulting in increased infectious complications after prostate biopsy. In our study we aimed to quantify the percentage of older northwestern Ohio males harboring ciprofloxacin-resistant bacteria in the rectal vault and to assess if resistance is increasing over time.

Methods: After Institutional Review Board approval, a retrospective chart review of all patients who underwent rectal swab culture within the Department of Urology at The University of Toledo Medical Center between January 1, 2012 and December 31, 2015 was completed. Patient demographic data were collected including the presence of ciprofloxacin resistance bacteria. To test for significant differences, χ and analysis of variance (ANOVA) analyses were completed where applicable.

Results: During the study period 311 swabs for resistant organisms were completed. The average age at time of swab was 64 (± 8.7 standard deviation [SD]) years old. Resistance rates were 13.2%, 13.8%, 19.5%, and 13.3% in 2012, 2013, 2014, and 2015, respectively. We found no statistically significant difference in resistances across years. Additionally, previous biopsy and age were not associated with ciprofloxacin resistance.

Conclusions: Resistance to ciprofloxacin in the rectal vaults of older northwestern Ohio males is significant but appears to be stable over the study period. Previous biopsy and increased age do not appear to be risk factors for fluoroquinolone resistance. Given the relatively high rate of resistance in our population we recommend rectal swabs prior to prostate biopsy to assist in antibiotic agent choice.
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http://dx.doi.org/10.1089/sur.2017.317DOI Listing
November 2018

Bilirubin, a new therapeutic for kidney transplant?

Transplant Rev (Orlando) 2018 10 28;32(4):234-240. Epub 2018 Jun 28.

Department of Urology and Renal Transplant, Toledo, OH 43614, USA; Center for Hypertension and Personalized Medicine, Department of Physiology & Pharmacology, University of Toledo College of Medicine, Toledo, OH 43614, USA. Electronic address:

In patients with end-stage renal disease, kidney transplantation has been associated with numerous benefits, including increased daily activity, and better survival rates. However, over 20% of kidney transplants result in rejection within five years. Rejection is primarily due to a hypersensitive immune system and ischemia/reperfusion injury. Bilirubin has been shown to be a potent antioxidant that is capable of potentially reversing or preventing damage from reactive oxygen species generated from ischemia and reperfusion. Additionally, bilirubin has several immunomodulatory effects that can dampen the immune system to promote organ acceptance. Increased bilirubin has also been shown to have a positive impact on renal hemodynamics, which is critical post-transplantation. Lastly, bilirubin levels have been correlated with biomarkers of successful transplantation. In this review, we discuss a multitude of potentially beneficial effects that bilirubin has on kidney acceptance of transplantation based on numerous clinical trials and animal models. Exogenous bilirubin delivery or increasing endogenous levels pre- or post-transplantation may have therapeutic benefits.
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http://dx.doi.org/10.1016/j.trre.2018.06.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6535229PMC
October 2018

Comparative analysis of anticipated pain versus experienced pain in patients undergoing office vasectomy.

Can J Urol 2017 Apr;24(2):8744-8748

Department of Urology, University of Oklahoma Health Science Center, Oklahoma City, Oklahoma, USA.

Introduction: Advances in vasectomy technique have minimized patient discomfort; however fear of pain remains a primary concern. The objective is to determine how the anticipation of pain associated with vasectomy compares with patient's actual intraoperative experienced pain levels.

Materials And Methods: A cohort of patients undergoing clinic vasectomy was analyzed. Using visual analog pain scale patients were asked to rate their anticipated pain score (APS) pre-procedure and then an experienced pain score (EPS) post-procedure. Patients were also stratified by APS scores (high versus low). Changes in pain score were compared across these groups. Pain scores stratified by age, race, narcotics use, psychiatric history, and prior surgical history were also compared.

Results: In the 172 patients included, the average pre-op APS was 5.2 (95% CI 4.3-5.6), while post-op EPS was 2.1 (95% CI 1.8-2.4). Patients were stratified into 'high' (6-10) and 'low' (0-5) pre-op APS groups. The average drop in pain scores was found to be significantly larger in the 'high' versus the 'low' APS groups (4.66 versus 1.65 p < 0.001). No statistical difference was noted in the change in pain scores based on age, race, prior surgical history, chronic narcotics use or psychiatric history. Both groups tolerated the procedure well, with the mean EPS of 2.56 for the 'high' and 1.73 for the 'low' APS group (p < 0.05).

Conclusions: The actual pain experienced by a patient is significantly lower than their anticipation of vasectomy pain, which will aid clinicians in appropriately counseling patients and minimizing pre-procedural anxiety.
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April 2017

Deciphering the Roles of Thiazolidinediones and PPAR in Bladder Cancer.

PPAR Res 2017 28;2017:4810672. Epub 2017 Feb 28.

Center for Hypertension and Personalized Medicine, Department of Physiology & Pharmacology, University of Toledo College of Medicine, Toledo, OH 43614, USA; Department of Urology, University of Toledo College of Medicine, Toledo, OH 43614, USA.

The use of thiazolidinedione (TZD) therapy in type II diabetic patients has proven useful in the lowering of blood glucose levels. However, recent investigations have shown that there may be potential health concerns associated, including the risk of developing bladder cancer as well as complications in the cardiovasculature. TZDs are ligands for the nuclear receptor PPAR, and activation causes lipid uptake and insulin sensitization, both of which are critical processes for diabetic patients whose bodies are unable to utilize insulin effectively. Several studies have shown that PPAR/TZDs decrease IGF-1 levels and, thus, reduce cancer growth in carcinomas such as the pancreas, colon, liver, and prostate. However, other studies have shed light on the potential of the receptor as a biomarker for uroepithelial carcinomas, particularly due to its stimulatory effect on migration of bladder cancer cells. Furthermore, PPAR may provide the tumor-promoting microenvironment by de novo synthesis of nutrients that are needed for bladder cancer development. In this review, we closely examine the TZD class of drugs and their effects on PPAR in patient studies along with additional molecular factors that are positive modulators, such as protein phosphatase 5 (PP5), which may have considerable implications for bladder cancer therapy.
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http://dx.doi.org/10.1155/2017/4810672DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5350343PMC
February 2017

Glucuronidation and UGT isozymes in bladder: new targets for the treatment of uroepithelial carcinomas?

Oncotarget 2017 Jan;8(2):3640-3648

Department of Physiology & Pharmacology, Center for Hypertension and Personalized Medicine, University of Toledo College of Medicine, Toledo, OH, USA.

Bladder cancer has been linked to numerous toxins which can be concentrated in the bladder after being absorbed into the blood and filtered by the kidneys. Excessive carcinogenic load to the bladder urothelium may result in the development of cancer. However, enzymes within the bladder can metabolize carcinogens into substrates that are safer. Importantly, these proteins, namely the UGT's (uridine 5'-diphospho-glucuronosyltransferases), have been shown to possibly prevent bladder cancer. Also, studies have shown that the UGT1 expression is decreased in uroepithelial carcinomas, which may allow for the accumulation of carcinogens in the bladder. In this review, we discuss the UGT system and its' protective role against bladder cancer, UGT genetic mutations that modulate risk from chemicals and environmental toxins, as well as targeting of the UGT enzymes by nuclear receptors.
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http://dx.doi.org/10.18632/oncotarget.12277DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5356909PMC
January 2017

p53-stabilizing agent CP-31398 prevents growth and invasion of urothelial cancer of the bladder in transgenic UPII-SV40T mice.

Neoplasia 2013 Aug;15(8):966-74

Department of Medicine, Hem-Onc Section, PC Stephenson Cancer Center, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.

The high prevalence of bladder cancer and its recurrence make it an important target for chemoprevention. About half of invasive urothelial tumors have mutations in p53. We determined the chemopreventive efficacy of a p53-stabilizing agent, CP-31398, in a transgenic UPII-SV40T mouse model of bladder transitional cell carcinoma (TCC) that strongly resembles human TCC. After genotyping, six-week-old UPII-SV40T mice (n = 30/group) were fed control (AIN-76A) or experimental diets containing 150 or 300 ppm of CP-31398 for 34 weeks. Progression of bladder cancer growth was monitored by magnetic resonance imaging. At 40 weeks of age, all mice were killed; urinary bladders were collected to determine weights, tumor incidence, and histopathology. There was a significant increase in bladder weights of transgenic versus wild-type mice (male: 140.2 mg vs 27.3 mg, P < .0001; female: 34.2 mg vs 14.8 mg, P < .0001). A significant decrease in the bladder tumor weights (by 68.6-80.2%, P < .0001 in males and by 36.9-55.3%, P < .0001 in females) was observed in CP-31398-treated mice. Invasive papillary TCC incidence was 100% in transgenic mice fed control diet. Both male and female mice exposed to CP-31398 showed inhibition of invasive TCC. CP-31398 (300 ppm) completely blocked invasion in female mice. Molecular analysis of the bladder tumors showed an increase in apoptosis markers (p53, p21, Bax, and Annexin V) with a decrease in vascular endothelial growth factor in transgenic mice fed CP-31398. These results suggest that p53-modulating agents can serve as potential chemopreventive agents for bladder TCC.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3730047PMC
http://dx.doi.org/10.1593/neo.13704DOI Listing
August 2013

Phase 3 clinical trial investigating the effect of selenium supplementation in men at high-risk for prostate cancer.

Prostate 2013 Feb 10;73(3):328-35. Epub 2012 Aug 10.

The University of Arizona Cancer Center, University of Arizona, Tucson, Arizona 85724, USA.

Purpose: This study was conducted to investigate the effect of Se supplementation on prostate cancer incidence in men at high risk for prostate cancer.

Methods: A Phase 3 randomized, double-blind, placebo-controlled clinical trial was conducted in 699 men at high risk for prostate cancer (prostate specific antigen (PSA) >4 ng/ml and/or suspicious digital rectal examination and/or PSA velocity >0.75 ng/ml/year), but with a negative prostate biopsy. Participants were randomized to receive daily oral placebo (N = 232), 200 µg selenium (N = 234), or 400 µg selenium (N = 233) as selenized yeast. They were followed every 6 months for up to 5 years. The time to diagnosis of prostate cancer was compared between treatment groups using the Cox proportional hazards model.

Result: Compared to placebo, the hazard ratios [95% confidence intervals] for risk of developing prostate cancer in the selenium 200 µg/day or the selenium 400 µg/day group were 0.94 [0.52, 1.7] and 0.90 [0.48, 1.7], respectively. PSA velocity in the selenium arms was not significantly different from that observed in the placebo group (P = 0.18 and P = 0.17, respectively).

Conclusion: Selenium supplementation appeared to have no effect on the incidence of prostate cancer in men at high risk. In conjunction with results of other studies, these data indicate that selenium supplementation may not have a role in prostate cancer chemoprevention.
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http://dx.doi.org/10.1002/pros.22573DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4086804PMC
February 2013

A comparative study of seed localization and dose calculation on pre- and post-implantation ultrasound and CT images for low-dose-rate prostate brachytherapy.

Phys Med Biol 2009 Sep 28;54(18):5595-611. Epub 2009 Aug 28.

Department of Radiation Oncology, University of Oklahoma Health Sciences Center, 825 NE 10th Street, OUPB 1430, Oklahoma City, OK 73104, USA.

This work investigates variation in the volume of the prostate measured at different stages through the prostate brachytherapy procedure for 30 patients treated with I-125 radioactive seeds. The implanted seeds were localized on post-implantation ultrasound (US) images and the effect of prostate enlargement due to edema on dose coverage for 15 patients was studied. The volume of the prostate was measured at four stages as follows: (a) 2-3 weeks prior to implantation using US imaging, (b) then at the start of the intra-operative prostate brachytherapy procedure on the day of the implant, (c) immediately post-implantation using US imaging in the operating room and (d) finally by CT imaging at nearly 4 weeks post-implantation. Comparative prostate volume studies were performed using US imaging stepper and twister modes. For the purpose of this study, the implanted seeds were localized successfully on post-implant ultrasound twister images, retrospectively. The plans using post-implant US imaging were compared with intra-operative plans on US and plans created on CT images. The prostate volume increases about 10 cm(3) on average due to edema induced by needle insertion and seed loading during implantation. The visibility of the implanted seeds on US twister images acquired post-implantation is as good as those on CT images and can be localized and used for dose calculation. The dose coverage represented by parameters such as D90 (dose covering 90% of the volume) and V100 (volume covered by 100% dose) is poorer on plans performed on post-implantation twister US studies than on the intra-operative live plan or the CT scan performed 4 weeks post-operatively. For example, the mean D90 difference on post-implantation US is lower by more than 15% than that on pre-implantation US. The volume enlargement of the prostate due to edema induced by needle insertion and seed placement has a significant effect on the quality of dosimetric coverage in brachytherapy prostate seed implants. Here, we introduced a new approach based on the use of post-implant US twister images to correct for prostate enlargement intra-operatively. Besides the ability to localize the seeds and superior soft tissue visibility, the twister US images include effects of the enlargement of the prostate gland and seed migration during the implantation procedure.
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http://dx.doi.org/10.1088/0031-9155/54/18/016DOI Listing
September 2009

Sensitivity of bladder cancer cells to curcumin and its derivatives depends on the extracellular matrix.

Anticancer Res 2007 Mar-Apr;27(2):737-40

Department of Urology, Oklahoma University Health Sciences Center, Oklahoma City, OK 73104, USA.

Because the response of cancer cells to chemotherapeutic agents depends upon the supporting extracellular matrix (ECM), the response in vivo may not be reproduced in 2-dimensional cell culture. The dose-response to curcumin and two derivatives by bladder cancer cells grown on both normal (SISgel) and cancer-derived ECM (Matrigel) and on plastic were contrasted. Cells grown on Matrigel were resistant to curcumins, but cells growing on SISgel, which mimic cancer cells suppressed by normal ECM, were nearly as sensitive as cells grown on plastic. SV40-immortalized urothelial cells, which are models for premalignant cells, were the most sensitive, but even aggressive cell lines were nearly as sensitive when grown on SISgel as on plastic. Curcumin response depends highly on the supporting ECM, and cells grown on plastic poorly models cells growing on natural ECM. Curcumin could prove an effective chemopreventive for bladder cancer recurrence when administered intravesically post-therapy.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2604907PMC
May 2007

Prostatitis and serum prostate-specific antigen.

Curr Urol Rep 2005 Jul;6(4):307-12

Department of Urology, Louisiana State University Health Sciences Center, Shreveport, LA 71130, USA.

Prostatitis is an inflammatory condition of the prostate and has been divided into four categories according to the National Institutes of Health classification. This article reviews the various types of prostatitis and their effect on serum prostate-specific antigen levels. Various proposed mechanisms of this elevation include leakage of prostate-specific antigen (PSA) into the blood stream, hypervascularity, and altered vascular permeability secondary to inflammation. Acute prostatitis can lead to an increase in PSA, which usually returns to normal levels with appropriate antibiotics within 1 to 3 months. Patients with chronic prostatitis have a less well-defined decrease in PSA after an antibiotic course. Whether a course of antibiotics prior to biopsy increases the yield has not been well established. Asymptomatic inflammation of the prostate has been recognized to be an important confounding factor in patients with an elevated PSA. Inflammation has been proposed to be a precursor of prostate adenocarcinoma.
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http://dx.doi.org/10.1007/s11934-005-0029-yDOI Listing
July 2005