Publications
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Improved 24-hour urine parameters associated with reduced symptomatic kidney stone recurrence
Sui W, Yang H, Escobar MC, Maalouf F, Suarez P, Chi T, Stoller ML. Urolithiasis. 2025 Dec 22;54(1):8. doi: 10.1007/s00240-025-01910-1. PMID: 41428069
This study addressed a persistent criticism of 24-hour urine testing: does actually improving abnormal values reduce stone recurrence? Looking at 200 patients with repeat testing and initial abnormalities, we found that patients who consistently normalized their calcium and citrate levels had significantly fewer stone events. Using a composite severity score that aggregates multiple urine parameters, we showed that worse initial scores predicted more recurrence (0.09 vs 0.31 stone events per year for lowest vs highest quartiles). More importantly, patients whose scores improved or stabilized over time had substantially reduced recurrence risk regardless of starting severity. This provides concrete evidence that metabolic intervention works—fixing the numbers on the test actually correlates with fewer stones. It's a meaningful counter to skeptics who question whether 24-hour urine monitoring matters clinically.
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Integrated AAV optimization enables efficient gene delivery to kidney in murine and human tissue
Garcia FG, Moreno MR, Chetty S, Johnson N, An A, Sostena J, Thompson L, Wang J, Charu V, Lee J, Meyer N, Stoller M, Yang H, Boutagy N, DiRito J, Tietjen G, Toscano CA, Garcia-Gonzalez M, Church G, Kay M, Thakor A, Bhalla V, Maxim D. Res Sq [Preprint]. 2025 Oct 24:rs.3.rs-7925411. doi: 10.21203/rs.3.rs-7925411/v1. PMID: 41282112
About 10% of nephrology patients have genetic causes of kidney disease that could theoretically be cured with gene therapy, but delivering genetic cargo to kidney cells has been a major obstacle. This study systematically optimized multiple variables—promoter, payload, genome configuration, enzymatic priming, viral capsid type, dose, and delivery route—to maximize kidney transduction using adeno-associated virus (AAV). The result was 40-60% transduction of kidney tubules in mice using an optimized AAV9 construct, among the highest efficiencies reported. We developed a machine learning tool for unbiased quantification and demonstrated proof-of-concept AAV transduction in live human kidney tissue using ex vivo perfusion. The work provides a technical roadmap for moving kidney gene therapy toward clinical translation, though the jump from mouse to human remains significant and novel capsids lack the safety track record of FDA-approved versions used in other organs.
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Development and validation of an ultra-low-cost, open source normothermic ex vivo organ perfusion platform
Yang H, Higgins N, Chu S, Lee J, Meyer N, Hansen K, Saeed M, Ferreira R, Sorrentino TA, Mena J, Suarez P, Maluf FC, Sui W, Velasquez MC, Mann U, Braun H, Du J, Elmer J, Chi T, Roy S, Flake A, Gardner JM, Stoller M. bioRxiv [Preprint]. 2025 Oct 28:2025.10.27.684886. doi: 10.1101/2025.10.27.684886. PMID: 41279679
We developed a low-cost organ perfusion system to make ex vivo research more accessible. Commercial perfusion devices are expensive and designed for clinical transplantation, not laboratory investigation. We built a functional system for under $1,500 using recycled and repurposed components, incorporating innovations like a parallel flow resistor for low-flow perfusion and a magnet-stabilized containment bag to manage venous drainage. We validated the platform by perfusing porcine kidneys for 24 hours, then successfully autotransplanting them. We also demonstrated the system's versatility by stably perfusing non-transplantable human kidneys, spleens, and pancreases using human blood products. The goal is democratizing access to organ perfusion research—enabling labs without major funding to study organ biology, test therapeutics, and develop preservation strategies using donated research organs.
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A Multicenter Randomized Controlled Trial of Ambulatory Versus Inpatient Percutaneous Nephrolithotomy
Hosier GW, Beiko DT, Yang H, Sui W, Bayne D, Stoller ML, Chi TL. Eur Urol Focus. 2025 Sep;11(5):695-701. doi: 10.1016/j.euf.2025.09.002. Epub 2025 Oct 7. PMID: 41062420
This randomized controlled trial directly compared same-day discharge versus overnight hospitalization after PCNL at two academic centers. The 70 patients enrolled weren't easy cases—nearly half were obese, 41% had significant comorbidities, and a third had stones over 4cm. Complication rates were actually lower in the ambulatory group (6% vs 14%), though not statistically significant. Readmission rates were similar (6% vs 3%), as were stone-free rates (77% vs 71%). Multivariable analysis showed no evidence that sending patients home the same day was inferior. The study's main limitation is modest sample size, but the results support that ambulatory PCNL is reasonable at experienced centers even for complex patients—challenging assumptions that these cases require routine overnight observation.
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Financial toxicity in lower urinary tract symptoms amongst men
Sui W, Suarez P, Yang H, Escobar MCV, Maluf FC, Hall T, Azzawi SA, Gupta L, Chi T. BMC Urol. 2025 Aug 21;25(1):213. doi: 10.1186/s12894-025-01895-4. PMID: 40841616
This study examined financial toxicity—the economic harm patients experience from treatment costs—in men with lower urinary tract symptoms from BPH, extending a concept usually studied in cancer patients. Surveying 294 men through a national volunteer registry, 41% met criteria for financial toxicity. These men had significantly worse symptom scores and dramatically higher rates of incontinence (stress, urge, and mixed) compared to those without financial burden. Out-of-pocket spending on incontinence products was a major driver. Mixed incontinence was the strongest predictor of financial toxicity on multivariable analysis. The findings highlight that chronic benign conditions can create substantial ongoing costs—particularly when incontinence requires daily product use—and that financial strain correlates with disease severity, creating a potential cycle where undertreated symptoms lead to more expensive management needs.
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Bladder cancer variants share aggressive features including a CA125+ cell state and targetable TM4SF1 expression
Yang H, Song H, Yip E, Gilpatrick T, Chang K, Allegakoen P, Lu KL, Hui K, Pham JH, Kasap C, Kumar V, Gayle J, Stohr BA, Cornelia Ding CK, Wiita AP, Meng MV, Chou J, Porten SP, Huang FW. Nat Commun. 2025 Jun 17;16(1):5312. doi: 10.1038/s41467-025-59888-8. PMID: 40527915
Histologic variant (HV) subtypes of bladder cancer are clinically aggressive tumors that are more resistant to standard therapy compared to conventional urothelial carcinoma (UC). Little is known about the transcriptional programs that account for their biological differences. Here we show using single cell analysis that HVs harbor a tumor cell state characterized by expression of MUC16 (CA125), MUC4, and KRT24. This cell state is enriched in metastases, predicted to be highly resistant to chemotherapy, and linked with poor survival. We also find enriched expression of TM4SF1, a transmembrane protein, in HV tumor cells. Chimeric antigen receptor (CAR) T cells engineered against TM4SF1 protein demonstrated in vitro and in vivo activity against bladder cancer cell lines in a TM4SF1 expression-dependent manner, highlighting its potential as a therapeutic target.
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Packed Red Blood Cell and Whole Blood Perfusates during Ex Vivo Normothermic Perfusion for Assessment of High-Risk Donor Kidneys
Ahmadi A, Yang H, Jen KY, Fan S, Palma I, Sageshima J, Goussous N, Roshanravan B, Perez RV. Kidney360. 2025 Sep 1;6(9):1573-1585. doi: 10.34067/KID.0000000815. Epub 2025 May 7. PMID: 40333014
This study compared two blood-based perfusates for ex vivo normothermic perfusion of high-risk donor kidneys: leukocyte-depleted packed red blood cells (PRBC) versus whole blood. Eight paired kidneys that had been cold-stored for an average of 54 hours were perfused for three hours. PRBC-perfused kidneys performed substantially better—they had higher blood flow, produced six times more urine, and showed lower levels of kidney injury biomarkers. Metabolic profiling revealed that whole blood caused more severe disruption to amino acid metabolism and mitochondrial energy pathways. Lipid analysis showed whole blood triggered accumulation of membrane components like ceramides, suggesting cellular stress or damage, while PRBC kidneys remained relatively stable. The findings suggest that removing white blood cells from the perfusate may reduce inflammatory injury during machine perfusion, which matters for rehabilitating marginal donor kidneys before transplantation.
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New Technology in Percutaneous Nephrolithotomy: Application of Navigation System, Robotics, Artificial Intelligence, and Suction Access Sheath m
Taguchi K, Yang H, Bayne DB, Unno R, Hamamoto S, Chi T, Yasui T. Int J Urol. 2025 Jul;32(7):793-803. doi: 10.1111/iju.70057. Epub 2025 Apr 24. PMID: 40271897
This review surveys recent technological advances in PCNL for large kidney stones. Key developments include 3D navigation systems that provide better anatomical visualization, leading to improved targeting and fewer complications. Robotic platforms and automated needle-targeting systems like MONARCH aim to enhance precision while reducing radiation exposure. AI applications are emerging for preoperative planning and predicting outcomes. Suction access sheaths help with stone clearance and may reduce complications. The review synthesizes peer-reviewed evidence from the past five years on how these technologies are changing PCNL practice, though many remain in early adoption phases.
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Re-defining the interpretation of 24-h urine studies for stone formers
Sui W, Yang H, Velasquez MC, Stoller ML, Chi T. BJU Int. 2025 Apr;135(4):691-699. doi: 10.1111/bju.16659. Epub 2025 Jan 23. PMID: 39846125
This study investigated whether patients with more clinical risk factors for stones also have worse 24-hour urine results. Looking at 614 stone patients, researchers found that accumulating clinical risk factors did predict more stone recurrence—but when examining individual urine values, nothing differed significantly except calcium. The solution was developing a composite severity score combining multiple urine parameters. This score revealed what individual values obscured: higher-risk patients did have worse overall urine profiles, and the severity score independently predicted recurrence. The practical implication is that looking at urine abnormalities one by one may miss the bigger picture. A composite scoring approach could better identify which patients need aggressive intervention and help standardize how clinicians interpret these complex lab panels.
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Longer Preoperative Antibiotic Duration Prior to High-Risk Ureteroscopy Does Not Decrease Infectious Complications
Sui W, Yang H, Pepic L, Chang K, Shee K, Rompsaithong U, Bayne DB, Stoller ML, Chi T. J Endourol. 2025 Jan;39(1):34-41. doi: 10.1089/end.2024.0487. Epub 2024 Dec 4. PMID: 39628387
This study examined whether longer preoperative antibiotic courses reduce infections after ureteroscopy in high-risk patients (those with neurological conditions, bowel diversions, indwelling catheters, or existing stents/nephrostomy tubes). Among 405 patients, 68% received no preoperative prophylaxis, while others received varying durations up to 10+ days. Overall infection rates were 9% for UTI/pyelonephritis and 5% for SIRS/sepsis. The key finding: antibiotic duration didn't matter. No prophylaxis regimen—short or long—reduced postoperative infections on multivariable analysis. The only significant predictor was sex, with women having four times higher odds of UTI/pyelonephritis than men. For clinicians debating how long to treat colonized patients before surgery, this data suggests extended antibiotic courses may not be helping—and the field needs to look elsewhere for infection prevention strategies.
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The potential role of Sodium/Glucose Cotransporter 2 inhibitors in the treatment of cystinuria
Sui W, Yang H, Desai M, Chi T, Stoller M. Urolithiasis. 2024 Nov 26;52(1):168. doi: 10.1007/s00240-024-01666-0. PMID: 39589516
This preliminary study tested a creative hypothesis: could flooding the urinary tract with glucose prevent cystine stone growth via the Maillard reaction (a chemical reaction between sugars and amino acids)? Researchers used SGLT2 inhibitors—diabetes drugs that cause glucose to spill into urine—off-label in ten cystinuria patients. Comparing each patient's stone event rate before and during treatment over a median follow-up of about 14 months, 70% experienced fewer stone events and half maintained stable stone volume. Notably, most patients had negative cystine capacity at baseline (meaning standard therapy wasn't controlling their disease), yet seven of eight still improved on the SGLT2 inhibitor. Side effects were minimal—one patient stopped due to an adverse reaction, three had mild self-resolving symptoms. This is a small, uncontrolled case series, so the results are hypothesis-generating rather than definitive. But for cystinuria patients who fail conventional therapy, SGLT2 inhibitors represent an intriguing mechanistic approach worth studying formally.
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A Novel Machine-Learning Algorithm to Predict Stone Recurrence with 24-Hour Urine Data
Shee K, Liu AW, Chan C, Yang H, Sui W, Desai M, Ho S, Chi T, Stoller ML. J Endourol. 2024 Aug;38(8):809-816. doi: 10.1089/end.2023.0457. PMID: 39121452
This study attempted to build a machine learning model that predicts kidney stone recurrence using 24-hour urine data. Researchers trained seven different algorithms on 423 stone patients with urine tests and follow-up data, then validated the best performer on a separate group of 172 patients. A logistic regression model with ElasticNet regularization performed best, achieving an AUC of 0.65—moderate but not great discriminative ability. When restricted to only high-confidence predictions, accuracy improved substantially (AUC 0.82), though this presumably excludes many patients. The model validated reasonably well in the external cohort (AUC 0.64), and a simplified version using just four urine variables performed nearly as well as the full model. This represents incremental progress rather than a breakthrough. An AUC of 0.65 means the model is better than random but far from clinically transformative. Still, having any validated recurrence predictor could help stratify patients for prevention intensity or enrich clinical trial enrollment with likely recurrers.
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The Yield of Genetic Testing in Management of Nephrolithiasis
Pearce RJ, Sui W, Yang H, Chi T, Stoller M. Urology. 2024 Nov;193:27-34. doi: 10.1016/j.urology.2024.07.002. Epub 2024 Jul 9. PMID: 38992507
This study examined who should get genetic testing among kidney stone patients and what the yield actually is. Of 36 high-risk stone formers tested using a comprehensive panel, 39% had identifiable mutations—though only 14% had definitively pathogenic ones, including primary hyperoxaluria, cystinuria, and enamel-renal syndrome. The rest were variants of uncertain significance, which are harder to act on clinically. Notably, 24-hour urine results didn't reliably predict who had genetic abnormalities; only 6 of 14 patients with mutations had corresponding urine findings, including just 3 of 5 with known pathogenic mutations. For hyperoxaluria specifically, urine oxalate above 80 mg/day appeared to be a reasonable threshold for prompting genetic workup. The study highlights the tension in genetic testing for stones: a 39% hit rate sounds high, but uncertain variants create counseling challenges, and normal urine tests don't rule out genetic disease. Still, this provides some preliminary guidance on when testing makes sense.
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Renal Autotransplantation: Association Between Preoperative Disease Duration and Surgical Outcomes
Li KD, Pearce RJ, Sui W, Yang H, Freise C, Roll GR, Chi T, Stoller ML. Urology. 2024 Oct;192:36-42. doi: 10.1016/j.urology.2024.06.050. Epub 2024 Jun 26. PMID: 38942394
This study asked whether waiting longer before performing renal autotransplantation leads to worse outcomes. Researchers compared 72 patients divided into early (within one year of diagnosis/initial treatment) versus delayed (beyond one year) groups. The delayed cohort had been dealing with their disease for a median of nearly two years versus about five months for the early group. Despite this substantial difference in disease duration, outcomes were essentially identical: no significant differences in aborted surgeries, perioperative complications, long-term complications, or kidney function changes. This held true even after adjusting for numerous patient factors. The clinical relevance is straightforward—surgeons and patients shouldn't feel pressured to rush into autotransplantation out of fear that waiting will compromise results. Complex cases that require time for optimization, additional workup, or patient decision-making can proceed on their own timeline without penalty.
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Case presentation and review of renal autotransplantation for nutcracker syndrome
Li KD, Bowman MS, Yang H, Sui W, Freise C, Stoller M. Urol Case Rep. 2024 Apr 3;54:102717. doi: 10.1016/j.eucr.2024.102717. eCollection 2024 May. PMID: 38617183
Nutcracker Syndrome (NCS) is characterized by entrapment of the left renal vein, leading hematuria, flank pain, and proteinuria. We evaluated the efficacy of renal autotransplantation as a curative treatment for NCS through a review and case report. 55 patients from 18 studies were analyzed, with a combined 91% success rate of symptom resolution or improvement post-autotransplantation. In our case report, a 25-year-old man with severe NCS received laparoscopic nephrectomy and autotransplant, resulting in symptom resolution at 3.1 years follow up. Further research should confirm these findings and refine patient selection criteria and surgical techniques.
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Reimagining Ambulatory Care in Urology: Conversion of the Urology Clinic into a Procedure Center Improves Patient's Experience
Hamouche F, Hakam N, Unno R, Ahn J, Yang H, Bayne D, Stoller ML, Smith S, Finlayson E, Smith J, Chi T. Telemed J E Health. 2024 Mar;30(3):748-753. doi: 10.1089/tmj.2023.0272. Epub 2023 Oct 20. PMID: 37862049
This study examined what happened when a urology clinic restructured during COVID-19, converting physical clinic space exclusively for procedures while shifting all routine visits to telehealth. Staff were assigned to focus on one modality per day rather than juggling both. Comparing pre-pandemic (2019) to pandemic-era (2020) periods, procedures jumped from 29% to 45% of in-person visits. Despite lower total charges and relative value units, actual revenue increased slightly—driven by the higher reimbursement procedures generate. Patient satisfaction improved across multiple metrics: more patients would recommend the practice, reported better overall access, and felt visits moved along more efficiently. The broader message is that the forced pandemic experiment revealed a potentially better model—dedicating clinic space to higher-value procedures while handling routine follow-ups virtually may simultaneously improve patient experience, operational efficiency, and financial performance. This is potentially a blueprint for how outpatient urology practices could operate going forward.
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Effects of standardized language on remote ultrasound-guided percutaneous nephrolithotomy training: A mixed-methods explorative pilot study
Denisov D, Castro-Olmo C, Charondo LB, Yang H, Van Schaik S, Bayne D. Heliyon. 2023 Aug 30;9(9):e19629. doi: 10.1016/j.heliyon.2023.e19629. eCollection 2023 Sep. PMID: 37809923
This pilot study tested whether standardized terminology for describing ultrasound probe and needle movements could improve remote teaching of kidney access for PCNL. Fifteen urology residents were randomized to either receive labeled images with predetermined terms for movements or unlabeled images, then practiced US-guided renal access on a mannequin with remote faculty guidance. The quantitative results—number of attempts and time to achieve access—showed no significant difference between groups. However, focus group discussions revealed something important: residents found that standardized terminology reduced confusion and made remote feedback clearer and more actionable. The takeaway is that while this small study couldn't demonstrate measurable performance differences, having everyone speak the same language during remote procedural training appears to improve communication quality. As telemedicine and remote education expand, establishing shared vocabulary for describing spatial movements could help overcome the inherent limitations of not being physically present with learners.
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Voided volume may not impact stone outcomes: Review of a large institutional nephrolithiasis cohort
Shee K, Chan C, Yang H, Sui W, Bowman M, Hamouche F, Charondo LB, Ho S, Chi T, Stoller ML. BJUI Compass. 2023 Apr 6;4(5):556-561. doi: 10.1002/bco2.216. eCollection 2023 Sep. PMID: 37636214
This study questioned a cornerstone of kidney stone prevention advice: drink more fluids. Researchers analyzed 450 stone patients with 24-hour urine data and tracked their stone events over time. Surprisingly, they found no overall association between urine volume and stone recurrence—patients who made more urine didn't have fewer stone events. This held true even after controlling for factors like age, gender, BMI, and sodium intake. The one exception: patients who form calcium oxalate dihydrate stones specifically did show a significant benefit from higher urine output. The provocative implication is that the blanket recommendation to "drink more water" may not help everyone equally. Rather than one-size-fits-all advice, identifying which stone formers actually benefit from increased fluids could represent a more targeted, precision medicine approach to prevention, a challenge to what is currently universal guideline advice.
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Clinical and postoperative characteristics of stentless ureteroscopy patients: a prospective analysis from ReSKU
Hamouche F, Unno R, Hakam N, Charondo LB, Yang H, Ahn J, Bayne DB, Stoller ML, Chi T. Can J Urol. 2023 Jun;30(3):11532-11537. PMID: 37344463
This study looked at outcomes in kidney stone patients who didn't receive a ureteral stent after ureteroscopy—a practice that remains somewhat controversial. Of 470 ureteroscopy patients, about 20% went stentless. These tended to be cases with smaller stone burden, shorter operative times, no access sheath used, or patients who already had a stent in place beforehand. The key finding: stentless patients reported significantly less blood in their urine and fewer bothersome urinary symptoms afterward, with no increase in complications (15% vs 12%, not statistically different). No stentless patient needed emergency stent placement. When they looked at what actually predicted complications, it was not the absence of a stent, but obesity, stones 1cm or larger, and positive preoperative urine cultures. The practical message is that for well-selected patients with straightforward ureteroscopies, skipping the stent can spare them the discomfort that stents notoriously cause without compromising safety.
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A Novel Standardized Morbidity and Mortality Process to Promote Discourse, Improve Education, and Facilitate Practice Change: The M-PROVE Model
Bowman M, Yang H, Ahn J, Carroll PR, Hampson LA. Urol Pract. 2023 Jul;10(4):391-397. doi: 10.1097/UPJ.0000000000000411. Epub 2023 May 10. PMID: 37228231
This study describes how one institution redesigned their morbidity and mortality (M&M) conference to make it more educational and less punitive. The changes included forming a faculty-resident oversight committee to review cases, creating standardized presentation templates and moderation structure, and tracking quality improvement initiatives that came out of discussions. They surveyed department members before and after implementing these changes. The results were striking: scores improved significantly across nearly every measure—perceived quality, educational value, relevance, inclusiveness, and identification of systems issues. The overall rating jumped from 3.36 to 4.20 on a 5-point scale. The only metric that didn't reach statistical significance was whether the environment felt non-threatening, though it still trended positive. These improvements held across faculty, residents, and both genders. The bottom line is that a structured, committee-driven approach to M&M conferences can transform them from dreaded blame sessions into genuinely valuable learning and quality improvement opportunities.
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Ultrasound-Only Percutaneous Nephrolithotomy Is Safe and Effective Compared to Fluoroscopy-Directed Percutaneous Nephrolithotomy
Hosier GW, Hakam N, Hamouche F, Cortez X, Charondo L, Yang H, Chan C, Chang K, Unno R, Sui W, Bayne DB, Stoller ML, Chi T. J Endourol. 2023 Jun;37(6):634-641. doi: 10.1089/end.2022.0761. Epub 2023 May 9. PMID: 37051696
This study compared outcomes between PCNL performed using only ultrasound guidance versus the traditional approach using fluoroscopy (X-ray). Looking at nearly 300 patients from a single center, researchers found no meaningful difference in complication rates (15% vs 16%) or stone-free rates (71% vs 65%) between ultrasound-only and fluoroscopy-guided procedures. These findings held up even after adjusting for patient and stone complexity factors. The ultrasound-only approach actually had advantages: procedures were about 25 minutes shorter on average, and patients avoided a mean radiation dose of 10 mGy. The takeaway is that skilled operators can safely perform PCNL without any fluoroscopy, achieving equivalent results while eliminating radiation exposure for both patients and surgical staff—a meaningful benefit given that stone patients often need multiple procedures over their lifetime.
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Maternal family history of urolithiasis is associated with earlier age of onset of stone disease
Unno R, Taguchi K, Hosier G, Usawachintachit M, Sui W, Yang H, Hamouche F, Bayne D, Stoller M, Chi T. World J Urol. 2023 Jan;41(1):241-247. doi: 10.1007/s00345-022-04221-x. Epub 2022 Dec 11. PMID: 36504337
This study examined how detailed family history affects kidney stone disease severity and timing. Looking at over 1,500 stone patients, researchers found that 39% had at least one family member with stones—and these patients were significantly more likely to have recurrent stones (38% vs 28%) over the follow-up period. Any family history increased recurrence risk by about 60%. But the details mattered: having both first- and second-degree relatives with stones more than doubled recurrence risk and tripled the odds of developing stones at a younger age. Interestingly, stones on your mother's side of the family were a stronger predictor of early onset than paternal-side history. The clinical implication is that asking patients specifically about which relatives have stones could help identify who needs more aggressive prevention strategies and closer monitoring.
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Determinants of ureteral obstruction after percutaneous nephrolithotomy
Lee HH, Yang H, Martin-Tuite P, Unno R, Hamouche F, Ahn J, Bayne D, Stoller M, Chi T. Urolithiasis. 2022 Dec;50(6):759-764. doi: 10.1007/s00240-022-01365-8. Epub 2022 Oct 14. PMID: 36239748
This study aimed to figure out why some patients develop ureteral obstruction after percutaneous nephrolithotomy (PCNL) and which patients might need longer drainage. Using registry data from 241 PCNL cases, researchers checked whether urine was flowing down the ureter on the first day after surgery—about 32% of patients had no flow, indicating obstruction. Three factors significantly increased obstruction risk: accessing the kidney through a non-lower pole location (nearly 3x higher odds), having stones located outside the renal pelvis (2.6x higher odds), and having ureteroscopy performed at the same time (about 2x higher odds). Interestingly, factors one might expect to matter—like BMI, total stone burden, blood loss, and operative time—didn't affect outcomes. The practical takeaway is that surgeons can use these risk factors to anticipate which patients may need a nephrostomy tube left in place longer rather than relying on a ureteral stent alone.
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The endoplasmic reticulum stress response in prostate cancer
de la Calle CM, Shee K, Yang H, Lonergan PE, Nguyen HG. Nat Rev Urol. 2022 Dec;19(12):708-726. doi: 10.1038/s41585-022-00649-3. Epub 2022 Sep 27. PMID: 36168057
In order to proliferate in unfavourable conditions, cancer cells can take advantage of the naturally occurring endoplasmic reticulum-associated unfolded protein response (UPR) via three highly conserved signalling arms: IRE1α, PERK and ATF6. All three arms of the UPR have key roles in every step of tumour progression: from cancer initiation to tumour growth, invasion, metastasis and resistance to therapy. At present, no cure for metastatic prostate cancer exists, as targeting the androgen receptor eventually results in treatment resistance. New research has uncovered an important role for the UPR in prostate cancer tumorigenesis and crosstalk between the UPR and androgen receptor signalling pathways. With an improved understanding of the mechanisms by which cancer cells exploit the endoplasmic reticulum stress response, targetable points of vulnerability can be uncovered.
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Ex vivo human testes as a practical model to simulate ultrasound-guided testicular cell transplantation for human fertility restoration
Yang H, Lindsey JP 2nd, Gillis-Buck EM, Srirangapatanam S, Rosen JE, Hussein AA, Smith JF. F S Sci. 2021 May;2(2):135-140. doi: 10.1016/j.xfss.2021.04.003. Epub 2021 Apr 19. PMID: 35559748
Researchers developed a practice model for testicular cell transplantation (TCT)—a potential future fertility treatment—using human testes removed during orchiectomy procedures. The technique involves injecting cellular material into the rete testis and watching it flow backward into the seminiferous tubules where sperm are made. They practiced on 30 testes from 16 patients, injecting contrast dye, blue dye, and fluorescent-labeled cells while using ultrasound to guide the needle and track where the material went. About 57% of injections showed successful filling on ultrasound, and they confirmed that what looked successful on imaging actually corresponded to material reaching the tubules on microscopic examination. The main point is that this is a learnable skill with a real learning curve, so having a way to practice on human tissue before attempting it in actual patients is important groundwork for eventually bringing this technique to the clinic.
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Plant-based diet index and erectile dysfunction in the Health Professionals Follow-Up Study
Yang H, Breyer BN, Rimm EB, Giovannucci E, Loeb S, Kenfield SA, Bauer SR. BJU Int. 2022 Oct;130(4):514-521. doi: 10.1111/bju.15765. Epub 2022 Jun 9. PMID: 35484829
This study followed nearly 22,000 men aged 40-75 over time to see whether eating a plant-based diet affected their risk of developing erectile dysfunction. Researchers tracked diet and ED status every four years, distinguishing between healthy plant foods (whole grains, fruits, vegetables) and unhealthy ones (refined grains, sugary drinks, sweets). The results varied by age: men in their 60s who ate the most healthy plant foods had an 18% lower risk of developing ED compared to those who ate the least. Meanwhile, men under 60 who ate more unhealthy plant foods had a 27% higher ED risk. We suggest promoting healthy plant-based eating as a sustainable way to help men preserve erectile function.
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Single-cell analysis of human primary prostate cancer reveals the heterogeneity of tumor-associated epithelial cell states
Song H, Weinstein HNW, Allegakoen P, Wadsworth MH 2nd, Xie J, Yang H, Castro EA, Lu KL, Stohr BA, Feng FY, Carroll PR, Wang B, Cooperberg MR, Shalek AK, Huang FW. Nat Commun. 2022 Jan 10;13(1):141. doi: 10.1038/s41467-021-27322-4. PMID: 35013146
Prostate cancer is the second most common malignancy in men worldwide and consists of a mixture of tumor and non-tumor cell types. To characterize the prostate cancer tumor microenvironment, we perform single-cell RNA-sequencing on prostate biopsies, prostatectomy specimens, and patient-derived organoids from localized prostate cancer patients. We uncover heterogeneous cellular states in prostate epithelial cells marked by high androgen signaling states that are enriched in prostate cancer and identify a population of tumor-associated club cells that may be associated with prostate carcinogenesis. ERG-negative tumor cells, compared to ERG-positive cells, demonstrate shared heterogeneity with surrounding luminal epithelial cells and appear to give rise to common tumor microenvironment responses. Finally, we show that prostate epithelial organoids harbor tumor-associated epithelial cell states and are enriched with distinct cell types and states from their parent tissues. Our results provide diagnostically relevant insights and advance our understanding of the cellular states associated with prostate carcinogenesis.
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Utility of Blue Light Cystoscopy for Post-bacillus Calmette-Guérin Bladder Cancer Recurrence Detection: Implications for Clinical Trial Recruitment and Study Comparisons
Chappidi MR, Yang H, Meng MV, Bivalacqua TJ, Daneshmand S, Holzbeierlein JM, Kaimakliotis HZ, Konety B, Liao JC, Pohar K, Steinberg GD, Taylor JM, Tyson MD, Willard B, Lotan Y, Porten SP, Kates M. J Urol. 2022 Mar;207(3):534-540. doi: 10.1097/JU.0000000000002308. Epub 2021 Oct 25. PMID: 34694916
This study looked at whether blue light cystoscopy (BLC) improves cancer detection in bladder cancer patients who recently received BCG treatment, compared to standard white light cystoscopy (WLC) alone. Using registry data from 2014-2019, they analyzed 282 cystoscopies in patients who had BCG within the past year. About 45% of these exams found recurrent cancer. The key finding: 13% of recurrences would have been missed using white light alone—BLC caught 16 additional cases that WLC didn't see, and most of these (88%) were carcinoma in situ, a flat lesion that's notoriously hard to spot. The tradeoff was a 5% false-positive rate where BLC flagged something suspicious that turned out not to be cancer. We recommend considering BLC for high-risk patients on BCG, while noting that inconsistent use of this technology across institutions could complicate clinical trial comparisons for new bladder cancer therapies.
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The erector spinae plane block can facilitate outpatient stone surgery by reducing breakthrough pain
Yang H, Lee HH, Martin-Tuite P, Chappidi M, Bowman M, Hamouche F, Ahn J, Stoller M, Braehler M, Chi T. BJU Int. 2021 Nov;128(5):557-560. doi: 10.1111/bju.15526. Epub 2021 Jul 21. PMID: 34174145 Clinical Trial.
Pain is one of the main reasons patients cannot go home the same-day after percutaneous nephrolithotomy. In this study, we demonstrate that a single injection of local anesthetic to the nerves next to the spine can reduce postoperative pain levels and allow patients to be discharged safely and comfortably.
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Live Renal Ultrasonography Facilitates Double-J Ureteral Stent Insertion at the Bedside: A Pilot Study for the COVID-19 Era
Yang H, Chappidi M, Overland M, Ahn J, Bayne D, Chi T. J Endourol. 2021 Jul;35(7):1078-1083. doi: 10.1089/end.2020.0954. Epub 2020 Dec 17. PMID: 33261510
This small study tested whether doctors could place ureteral stents at the bedside using ultrasound guidance instead of in the operating room with fluoroscopy. Over about two months in spring 2020, we tried this approach on 8 patients with blocked ureters. It worked in 7 of 8 cases—the one failure was a patient with an impacted stone and scar tissue who needed surgery. No one had complications. The takeaway is that ultrasound-guided bedside stent placement appears feasible for most straightforward cases and offers a way to avoid the OR and radiation exposure, which is particularly useful when conserving hospital resources matters.
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Urethral Defect in Setting of Recurrent Urethral Foreign Body Insertion
Simms A, Chappidi M, Yang H, Hampson L, Breyer B, Cohen AJ. Urology. 2020 Mar;137:e12-e13. doi: 10.1016/j.urology.2019.11.024. Epub 2019 Nov 30. PMID: 31794812
We present a case of recurrent episodes of foreign body insertion into the urethra, ultimately resulting in urethral defect at the penoscrotal junction. We have decided against treating the urethral defect as it facilitates nonoperative retrieval of the urethral foreign bodies. We present our experience and rationale for the clinical management of this complex patient.
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Non-oncologic Indications for Male Fertility Preservation
Yang H, Ramstein J, Smith J. Curr Urol Rep. 2019 Jul 26;20(9):51. doi: 10.1007/s11934-019-0915-3. PMID: 31346775
Common scenarios in which male fertility could be irreversibly compromised include autoimmune conditions requiring treatment with cyclophosphamide, gender dysphoria prior to starting hormone therapy, military deployment, and critical illness. Fertility preservation should be considered with particular attention to the timing and logistics specific to each scenario. Recognition and familiarity with such situations will help physicians provide better counseling to patients and their families, improve the quality of decision-making, and ultimately reduce missed opportunities and regret.
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Spict, a cyst cell-specific gene, regulates starvation-induced spermatogonial cell death in the Drosophila testis
Chiang AC, Yang H, Yamashita YM. Sci Rep. 2017 Jan 10;7:40245. doi: 10.1038/srep40245. PMID: 28071722
Tissues stay healthy by constantly replacing old cells with new ones, adjusting this balance depending on conditions like food availability. In the fruit fly testis, we previously found that removing certain developing sperm cells helps protect stem cells during protein starvation. This study identifies a gene called spict, active in the surrounding support cells, that helps control this process. Spict becomes more active when these support cells clean up dying sperm cells, and this cleanup appears to help maintain the stem cells when nutrients are scarce.
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A mitochondrial DNA hypomorph of cytochrome oxidase specifically impairs male fertility in Drosophila melanogaster
Patel MR, Miriyala GK, Littleton AJ, Yang H, Trinh K, Young JM, Kennedy SR, Yamashita YM, Pallanck LJ, Malik HS. Elife. 2016 Aug 2;5:e16923. doi: 10.7554/eLife.16923. PMID: 27481326
Because mitochondria are passed down only from mothers, their DNA can sometimes build up mutations that harm males but not females—a phenomenon known as the “Mother’s Curse.” In this study, we discovered a mitochondrial mutation called COII(G177S) in fruit flies that makes males infertile by disrupting sperm development, while leaving females and other male traits unaffected. Some fly genetic backgrounds can completely reverse this infertility, suggesting that the rest of the genome can sometimes compensate for harmful mitochondrial mutations.
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The regulated elimination of transit-amplifying cells preserves tissue homeostasis during protein starvation in Drosophila testis.
Yang H, Yamashita YM. Development. 2015 May 15;142(10):1756-66. doi: 10.1242/dev.122663. PMID: 25968311
This study looks at how tissues adjust when nutrients, especially protein, are scarce. Using fruit flies (Drosophila), we found that the testes respond to protein starvation by removing developing sperm cells called spermatogonia, while keeping a smaller number of stem cells alive. The developing cells die because the supporting “cyst” cells around them trigger a controlled form of cell death (apoptosis). Interestingly, if this process is blocked, the stem cells also die and the whole tissue breaks down. This shows that getting rid of certain developing cells helps protect the stem cells and maintain healthy tissue during times of starvation.