Publications by authors named "Sudarshan Srirangapatanam"

9 Publications

  • Page 1 of 1

Mineralized Peyronie's plaque has a phenotypic resemblance to bone.

Acta Biomater 2021 Nov 21. Epub 2021 Nov 21.

Division of Biomaterials and Bioengineering, Department of Preventative and Restorative Dental Sciences, School of Dentistry, University of California San Francisco, California, United States of America; Department of Urology, School of Medicine, University of California, San Francisco, California, United States of America. Electronic address:

Mineralized Peyronie's plaque (MPP) impairs penile function. The association, colocalization, and dynamic interplay between organic and inorganic constituents can provide insights into biomineralization of Peyronie's plaque. Human MPPs (n = 11) were surgically excised, and the organic and inorganic constituents were spatially mapped using multiple high-resolution imaging techniques. Multiscale image analyses resulted in spatial colocalization of elements within a highly porous material with heterogenous composition, lamellae, and osteocytic lacuna-like features with a morphological resemblance to bone. The lower (520 ±179 mg/cc) and higher (1024 ± 155 mg/cc) mineral density regions were associated with higher (11%) and lower (7%) porosities in MPP. Energy dispersive X-ray and micro-X-ray fluorescent spectroscopic maps in the higher mineral density regions of MPP revealed higher counts of calcium (Ca) and phosphorus (P), and a Ca/P ratio of 1.48 ± 0.06 similar to bone. More importantly, higher counts of zinc (Zn) were localized at the interface between softer (more organic to inorganic ratio) and harder (less organic to inorganic ratio) tissue regions of MPP and adjacent softer matrix, indicating the involvement of Zn-related proteins and/or pathways in the formation of MPP. In particular, dentin matrix protein-1 (DMP-1) was colocalized in a matrix rich in proteoglycans and collagen that contained osteocytic lacuna-like features. This combined materials science and biochemical with correlative microspectroscopic approach provided insights into the plausible cellular and biochemical pathways that incite mineralization of an existing fibrous Peyronie's plaque. STATEMENT OF SIGNIFICANCE: Aberrant human penile mineralization is known as mineralized Peyronie's plaque (MPP) and often results in a loss of form and function. This study focuses on investigating the spatial association of matrix proteins and elemental composition of MPP by colocalizing calcium, phosphorus, and trace metal zinc with dentin matrix protein 1 (DMP-1), acidic proteoglycans, and fibrillar collagen along with the cellular components using high resolution correlative microspectroscopic techniques. Spatial maps provided insights into cellular and biochemical pathways that incite mineralization of fibrous Peyronie's plaque in humans.
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http://dx.doi.org/10.1016/j.actbio.2021.11.025DOI Listing
November 2021

Community Income, Healthy Food Access, and Repeat Surgery for Kidney Stones.

Urology 2021 Nov 20. Epub 2021 Nov 20.

University of California, San Francisco, Urology. Electronic address:

Objectives: To determine if limited food access census tracts (LFACTs) and food swamp census tracts (FSCTs) are associated with increased risk for repeat kidney stone surgery. And to elucidate the relationship between community-level food retail environment relative to community-level income on repeat stone surgery over time.

Methods: Data were abstracted from the UCSF Information Commons. Adult patients were included if they underwent at least one urologic stone procedure. Census tracts from available geographical data were mapped using Food Access Research Atlas data from the USDA Economic Research Service. Kaplan-Meier curves were employed to illustrate time to a second surgical procedure over five years, and log-rank tests were used to test for statistically significant differences. A multivariate Cox regression model was used to generate hazard ratios for undergoing second surgery by group.

Results: A total of 1496 patients were included in this analysis. Repeat stone surgery occurred in 324 patients. Kaplan-Meier curves demonstrated a statistically significant difference in curves depicting patients living in low income census tracts (LICTs) vs those not living in LICTs (p < 0.001). On Cox regression models, patients in LICTs had significantly higher risk of undergoing repeat surgery (p = 0.011). Patients from LFACTs and FSCTs did not have a significantly higher adjusted risk of undergoing second surgery (p = 0.11 and p = 0.88, respectively) CONCLUSIONS: : Income more so than food access associates with increased risk of repeat kidney stone surgery. Further research is needed to explore the interaction between low SES and kidney stone outcomes.
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http://dx.doi.org/10.1016/j.urology.2021.11.010DOI Listing
November 2021

Ectopic biomineralization in kidney stone formers compared to non-stone formers.

Transl Androl Urol 2020 Oct;9(5):2129-2137

Department of Urology, University of California San Francisco, San Francisco, CA, USA.

Background: Kidney stone formers (SFs) are at increased risk of stroke, myocardial infarction, and atherosclerosis of the carotid and coronary arteries. These cardiovascular and urologic pathologies can result from ectopic biomineral deposition. The objectives of this study are: (I) to evaluate risk factors for ectopic biomineralization, and (II) to characterize the overall burden of ectopic minerals in known SFs compared to non-stone formers (NSFs) matched for these risk factors.

Methods: Presence and quantity of biominerals at eight anatomic locations (abdominal aorta, common iliac arteries, pelvic veins, prostate or uterus, mesentery, pancreas, and spleen) were determined in a case control study by retrospective analysis of clinical non-contrast computed tomography scans obtained from 190 SFs and 190 gender- and age-matched NSFs (renal transplant donors). Predictors of biomineralization were determined using negative binomial regression. A subgroup of 140 SFs and 140 NSFs were matched for risk factors for systemic biomineralization, and mineralization was compared between these matched SFs and NSFs using ordinal logistic regression.

Results: Hypertension, hyperlipidemia, diabetes mellitus, and smoking were more common amongst SFs. Risk factors for increased systemic biomineralization included history of nephrolithiasis, male gender, older age, and history of hyperlipidemia. When controlling for these comorbidities, SFs had significantly increased biomineralization systemically and at the abdominal aorta, iliac arteries, prostate, mesentery, pancreas, and spleen compared to NSFs.

Conclusions: The current study provides evidence that SFs are at increased risk of biomineralization systemically, independent of common risk factors of atherosclerosis.
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http://dx.doi.org/10.21037/tau-19-927DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7658123PMC
October 2020

Novel measurement tool and model for aberrant urinary stream in 3D printed urethras derived from human tissue.

PLoS One 2020 11;15(11):e0241507. Epub 2020 Nov 11.

Department of Urology, University of California San Francisco, San Francisco, CA, United States of America.

Background: An estimated 10% of male adults have split or dribbled stream leading to poor hygiene, embarrassment, and inconvenience. There is no current metric that measures male stream deviation.

Objective: To develop a novel method to measure spray in normal and abnormal anatomical conformations.

Design, Setting, And Participants: We developed a novel platform to reliably describe spray. We used cadaveric tissues and 3D Printed models to study the impact of meatal shape on the urinary stream. Cadaveric penile tissue and 3D printed models were affixed to a fluid pump and used to simulate micturition. Dye captured on fabric allowed for spray detection.

Outcome Measurements And Statistical Analysis: Spray pattern area, deviation from normal location, and flowrates were recorded. Computational fluid dynamic models were created to study fluid vorticity.

Results And Limitations: Obstructions at the penile tip worsened spray dynamics and reduced flow. Ventral meatotomy improved flowrate (p<0.05) and reduced spray (p<0.05) compared to tips obstructed ventrally, dorsally or in the fossa navicularis. 3D models do not fully reproduce parameters of their parent cadaver material. The average flowrate from 3D model was 10ml/sec less than that of the penis from which it was derived (p = 0.03). Nonetheless, as in cadavers, increasing obstruction in 3D models leads to the same pattern of reduced flowrate and worse spray. Dynamic modeling revealed increasing distal obstruction was correlated to higher relative vorticity observed at the urethral tip.

Conclusions: We developed a robust method to measure urine spray in a research setting. Dynamic 3D printed models hold promise as a methodology to study common pathologies in the urethra and corrective surgeries on the urine stream that would not be feasible in patients. These novel methods require further validation, but offer promise as a research and clinical tool.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0241507PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7657556PMC
December 2020

Low Urologist Density Predicts High-Cost Surgical Treatment of Stone Disease.

J Endourol 2021 04 6;35(4):552-559. Epub 2020 Nov 6.

Department of Urology, University of California San Francisco, San Francisco, California, USA.

Lack of access to urologic specialists is approaching crisis levels as the number of urologists is decreasing, while the demand for urologic care is increasing. The financial implications of this have not been explored. The objective of this study is to examine the impact of access and other patient factors on cost to treat urolithiasis. We hypothesized that markers of poor access would associate with higher costs of surgical encounters for patients presenting with urolithiasis. A retrospective review of prospectively collected data from the Registry for Stones of the Kidney and Ureter (ReSKU) from September 2015 to July 2018 was conducted to investigate characteristics of surgical patients treated for urinary stone disease. Univariate analysis was performed using the Welch two-sample -test. Multivariate analysis was performed using logistic regression. Statistical analysis was performed in R version 3.5. When taking into account age, delayed presentation, procedure type, stone size >20 mm, American Society of Anesthesiologists (ASA) code, gender, race, income, distance, urologist density, body mass index, diabetes, infection, education, language, insurance, and stone complexity, patients undergoing percutaneous nephrolithotomy procedure ( < 0.001; odds ratio [OR] 12.9, confidence interval [CI] 4.05-48.5), urologist density in the bottom quartile ( = 0.014; OR 4.66, CI 1.40-16.9), diabetes ( = 0.018; OR 4.38, CI 1.32-15.6), and infection ( = 0.007; OR 4.51, CI 1.55-14.0) were the only variables statistically significant for association with top quartile of total cost. Surgical encounter costs are largely dictated by patient clinical factors, but low regional urologist density appears to independently predicted for high-cost stone surgery. Increasing patients' access to a urologist may prove to be financially beneficial in the longitudinal reduction in health care costs for stone disease.
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http://dx.doi.org/10.1089/end.2020.0676DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8080904PMC
April 2021

Characterizing voiding experiences of men choosing seated and standing positions.

Neurourol Urodyn 2020 11 23;39(8):2509-2519. Epub 2020 Sep 23.

Department of Urology, University of California San Francisco, San Francisco, California, USA.

Aims: Voiding positions and preferences in men are not well characterized. In this study, we aim to understand the interplay of voiding characteristics and their impact on voiding position.

Methods: We designed a 27-item survey to assess voiding characteristics and lower urinary tract symptoms (LUTS) severity in men seen in urology and other outpatient clinics. Participants included adult men patients and adult men accompanying patients at our institution's outpatient clinics. Data collected included demographics, International Prostate Symptom Score questionnaire, stream type (single, split, and dribble), voiding behavior, positional stream quality, and voiding bother.

Results: We received 195 completed surveys (80% response rate). Of men queried, 18% (35/195) preferred to sit while voiding. Overall, men who sit had a higher proportion of LUTS (66% [23/35] vs. 41% [66/160]; p = .01), more physical limitations affecting voiding choice (20% [7/35] vs. 3% [5/160]; (p = .001), and a lower desire to stand (6% [2/35] vs. 24% [38/160]; p = .02), compared to men who stand. Men who sit while voiding reported nearly double the amount of voiding associated bother (34% [12/35]) compared to men who stand (18% [28/160]; p = .04). Older aged men reported a similar rate of seated urination compared to younger men. The most common reasons to void seated included comfort and avoidance of spraying.

Conclusions: Our findings discourage the use of anecdotal beliefs founded on generalizable characteristics, such as age and stream type, to infer a patient's voiding characteristics. Open dialog with patients regarding voiding preferences may garner important information regarding overall urologic health and better inform urologic care.
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http://dx.doi.org/10.1002/nau.24523DOI Listing
November 2020

Role of core body temperature in nephrolithiasis.

BJU Int 2020 11 26;126(5):620-624. Epub 2020 Aug 26.

Department of Urology, University of California, San Francisco, CA, USA.

Objectives: To assess the role of core body temperature in urinary stone formation using a large clinical dataset.

Patients And Methods: We retrospectively collected 14 519 039 individual temperature measurements from 580 416 patients with medical history, laboratory values and medication history between 2013 and 2018 at a single institution. After exclusions and matching 2:1 (controls:cases) to account for confounding variables, 7104 patients with a history of urinary stones were identified.

Results: Patients with a history of urinary stones (cases) had an elevated mean (SD) oral temperature compared to matched controls, at 36.666 (0.17) vs 36.659 (0.20)°C (P = 0.012). Logistic regression of matched samples showed that higher core body temperature was predictive of a history of nephrolithiasis (odds ratio 1.21, 95% confidence interval 1.04-1.4; P = 0.015).

Conclusion: Core body temperature was significantly higher in patients with a history of urinary stones compared to matched controls, contrary to the anticipated thermodynamic considerations leading to crystal aggregation. Given that the core body temperature is elevated, rather than decreased, thermodynamic process driving stone formation is unlikely.
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http://dx.doi.org/10.1111/bju.15185DOI Listing
November 2020

Synchronous genitourinary lichen sclerosus signals a distinct urinary microbiome profile in men with urethral stricture disease.

World J Urol 2021 Feb 9;39(2):605-611. Epub 2020 Apr 9.

Department of Urology, Zuckerberg San Francisco General Hospital and Trauma Center, University of California-San Francisco, 1001 Potrero Suite 3A, San Francisco, CA, 94110, USA.

Purpose: Alterations in the urinary microbiome have been associated with urological diseases. The microbiome of patients with urethral stricture disease (USD) remains unknown. Our objective is to examine the microbiome of USD with a focus on inflammatory USD caused by lichen sclerosus (LS).

Methods: We collected mid-stream urine samples from men with LS-USD (cases; n = 22) and non-LS USD (controls; n = 76). DNA extraction, PCR amplification of the V4 hypervariable region of the 16S rRNA gene, and sequencing was done on the samples. Operational taxonomic units (OTUs) were defined using a > 97% sequence similarity threshold. Alpha diversity measurements of diversity, including microbiome richness (number of different OTUs) and evenness (distribution of OTUs) were calculated and compared. Microbiome beta diversity (difference between microbial communities) relationships with cases and controls were also assessed.

Results: Fifty specimens (13 cases and 37 controls) produced a 16S rRNA amplicon. Mean sample richness was 25.9 vs. 16.8 (p = 0.076) for LS-USD vs. non-LS USD, respectively. LS-USD had a unique profile of bacteria by taxonomic order including Bacillales, Bacteroidales and Pasteurellales enriched urine. The beta variation of observed bacterial communities was best explained by the richness.

Conclusions: Men with LS-USD may have a unique microbiologic richness, specifically inclusive of Bacillales, Bacteroidales and Pasteurellales enriched urine compared to those with non-LS USD. Further work will be required to elucidate the clinical relevance of these variations in the urinary microbiome.
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http://dx.doi.org/10.1007/s00345-020-03198-9DOI Listing
February 2021

Female Urethral Strictures: Review of Diagnosis, Etiology, and Management.

Curr Urol Rep 2019 Nov 8;20(11):74. Epub 2019 Nov 8.

Department of Urology, University of California, San Francisco, San Francisco, CA, USA.

Purpose Of Review: In this review, we describe the incidence, diagnosis, and management of urethral strictures in women.

Recent Findings: Definitive repair of urethral strictures in women traditionally utilizes vaginal and labial flaps. Oral mucosal buccal graft urethroplasty also has high success rates, with larger series demonstrating feasibility and durability. Urethral strictures in women are very rare. When they do occur, they are often difficult to diagnose, requiring a high index of suspicion. Women with urethral strictures often present with symptoms of obstructed urinary flow, such as incomplete emptying, straining, and elevated postvoid residual. First line, minimally invasive treatment consists of urethral dilation and urethrotomy, though urethrotomy is rarely performed. Repeat urethral dilation has low success rates compared with urethroplasty, which is a more definitive treatment.
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http://dx.doi.org/10.1007/s11934-019-0933-1DOI Listing
November 2019
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