Infiltrating lipid-rich macrophage subpopulations identified as a regulator of increasing prostate size in human benign prostatic hyperplasia.

Macrophages exhibit marked phenotypic heterogeneity within and across disease states, with lipid metabolic reprogramming contributing to macrophage activation and heterogeneity. Chronic inflammation has been observed in human benign prostatic hyperplasia (BPH) tissues, however macrophage activation states and their contributions to this hyperplastic disease have not been defined. We postulated that a shift in macrophage phenotypes with increasing prostate size could involve metabolic alterations resulting in prostatic epithelial or stromal hyperplasia. Single-cell RNA-seq of CD45+ transition zone leukocytes from 10 large (>90 grams) and 10 small (<40 grams) human prostates was conducted. Macrophage subpopulations were defined using marker genes. BPH macrophages do not distinctly categorize into M1 and M2 phenotypes. Instead, macrophages with neither polarization signature preferentially accumulate in large versus small prostates. Specifically, macrophage subpopulations with altered lipid metabolism pathways, demarcated by TREM2 and MARCO expression, significantly accumulate with increased prostate volume. TREM2 + and MARCO + macrophage abundance positively correlates with patient body mass index and urinary symptom scores. TREM2+ macrophages have significantly higher neutral lipid than TREM2- macrophages from BPH tissues. Lipid-rich macrophages were observed to localize within the stroma in BPH tissues. In vitro studies indicate that lipid-loaded macrophages increase prostate epithelial and stromal cell proliferation compared to control macrophages. These data define two new BPH immune subpopulations, TREM2+ and MARCO+ macrophages, and suggest that lipid-rich macrophages may exacerbate lower urinary tract symptoms in patients with large prostates. Further investigation is needed to evaluate the therapeutic benefit of targeting these cells in BPH.

Daily Ecological Momentary Assessments of Pain and Ability to Work After Ureteroscopy and Stenting.

Introduction: Ureteral stents can cause significant patient discomfort, yet the temporal dynamics and impact on activities remain poorly characterized. We employed an automated tool to collect daily ecological momentary assessments (EMAs) regarding pain and the ability to work following ureteroscopy with stenting. Our aims were to assess feasibility and better characterize the postoperative patient experience. Materials and Methods: As an exploratory endpoint within an ongoing clinical trial, patients undergoing ureteroscopy with stenting were asked to complete daily EMAs for 10 days postoperatively or until the stent was removed. Questionnaires were distributed through text messages and included a pain scale (0-10) and a single item from the validated Patient-Reported Outcomes Measurement Information System Ability to Participate in Social Roles and Activities instrument, as well as days missed from work or school. Results: Among the first 65 trial participants, 59 completed at least 1 EMA (overall response rate 91%). Response rates were >85% for each time point through postoperative day (POD)10. Median respondent age was 58 years (interquartile range [IQR] 50-67), and 56% were female. Stones were 54% renal and 46% ureteral, with a median diameter of 9 mm (IQR 7-10). Median stent dwell time was 7 days (IQR 6-8). Pain scores were highest on POD1 (median score 4) and declined on each subsequent day, reaching a median score of 2 on POD5. Sixty-three percent of patients on POD1 reported that they had trouble performing their usual work at least sometimes, but by POD5, this was <50% of patients. Patients who work or attend school reported a median of 1 day missed (IQR 0-2). Conclusions: An automated daily EMA system for capturing patient-reported outcomes was demonstrated to be feasible with sustained excellent engagement. Patients with stents reported the worst pain and interference with work on POD1, with steady improvements thereafter, and by POD5, the majority of patients had minimal pain or trouble performing their usual work. This work is associated with a registered clinical trial [NCT05026710].

How I Do It: Ureteroscopy and high-power holmium laser lithotripsy to treat renal stones.

In North America, ureteroscopy has become the most popular treatment modality for upper urinary tract urinary calculi. Herein we describe our technique for the treatment of renal stones with flexible ureteroscopy and high-power holmium laser lithotripsy. We discuss preoperative planning, intraoperative strategies, and laser settings for a high-frequency dusting technique with the goal to provide optimal patient outcomes.

Improving the Quality of Upper Urinary Tract Stone Surgery: External Validation of a Statewide Collaborative's Efforts to Reduce Emergency Department Visits After Ureteroscopy.

PURPOSE: The ROCKS (Reducing Operative Complications from Kidney Stones) program in MUSIC (Michigan Urological Surgery Improvement Collaborative) was created to optimize ureteroscopy outcomes. Through data collection, distribution of reports, patient education, and standardization of medication, post-ureteroscopy emergency department visits in Michigan have declined. It is unclear whether this is because of statewide quality efforts or due to national trends. We therefore sought to understand emergency department visit rates in Michigan compared to a national data set. MATERIALS AND METHODS: We compared the MUSIC ROCKS clinical registry in Michigan against a national cohort, Optum's de-identified Clinformatics Data Mart, from 2016-2021 (excluding Michigan). We identified patients who underwent ureteroscopy and the proportion who had a postoperative emergency department visit within 30 days. Emergency department rates were modeled over time, adjusting for age, gender, comorbidity, and ureteral stenting. RESULTS: We identified 24,688 patients in MUSIC ROCKS and 99,340 in the Clinformatics Data Mart database who underwent ureteroscopy. The risk-adjusted emergency department visit rate in MUSIC ROCKS significantly declined over the study period (10.5% in 2016 to 6.9% in 2021, P < 0.001) while the mean emergency department visit rate in the Clinformatics Data Mart cohort was 9.9% and did not change over time (9.6% in 2016 to 10% in 2021). Comparing emergency department visits between the cohorts, the MUSIC ROCKS rate significantly declined relative to the Clinformatics Data Mart (P < 0.001) over the study period. CONCLUSIONS: Postoperative emergency department visit rates in Michigan have declined significantly after ureteroscopy since the establishment of MUSIC ROCKS. This decline outpaced national rates, providing evidence that systematic quality initiatives can improve urological care.

The 2023 Stone-Free CT Mandate: Addressing the Two Sides of the Debate.

To the editors of the Journal of Endourology, we write to express our reservations in the recent announcement that starting in 2023 all reporting of stone-free rates be based on CT.

Initial Experience Performing "Cautery-Free Waterjet Ablation of the Prostate".

Introduction: Herein, we describe our initial experience performing waterjet ablation of the prostate without electrocautery. Materials and Methods: A retrospective review of patients undergoing Aquablation for benign prostatic hyperplasia between February and September 2019 was performed. A standardized perioperative protocol for optimizing hemostasis was implemented. The primary endpoint was to define bleeding complications perioperatively and up to 30 days postoperatively after Aquablation. Bleeding complications included hematuria requiring prolonged continuous bladder irrigation, drop in hemoglobin requiring transfusion, or take back to operating room for evacuation of bladder clots and bladder fulguration. Bivariable analysis using Fisher's exact test and unpaired t-tests were used to identify factors associated with bleeding complications. Results: Thirty-two patients underwent Aquablation over the study period. Average preoperative international prostate symptom score was 20 (range: 13-34) and Qmax was 7 mL/s (range: 0-11). Mean prostate volume was 65 cc (range: 30-200 cc). Average perioperative change in hemoglobin was 1.3 g/dL (range: -0.3 to 4.2 g/dL). Eight patients (25%) experienced bleeding complications. Three (9.4%) required blood transfusions. On Fisher's exact test, prostate volume (91 cc vs 55 cc; p = 0.0361) and preoperative prostate-specific antigen (6.6 vs 2.9; p = 0.0218) were associated with postoperative bleeding. Conclusions: Performing waterjet ablation of the prostate without the use of electrocautery after waterjet treatment to control bleeding resulted in significant bleeding complications (25% of our cohort) during our initial experience. A combination of traction and focal bladder neck electrocautery is the best strategy to minimize bleeding complications after Aquablation.

Pain management strategies in penile implantation.

The opioid epidemic continues to be a serious public health concern. Many have pointed to prescription drug misuse as a nidus for patients to become addicted to opioids and as such, urologists and other surgical subspecialists must critically define optimal pain management for the various procedures performed within their respective disciplines. Controlling pain following penile prosthesis implantation remains a unique challenge for urologists, given the increased pain patients commonly experience in the postoperative setting. Although most of the existing urological literature focuses on interventions performed in the operating room, there are many studies that examine the role of preoperative adjunctive pain medicine in diminishing postoperative narcotic requirements. There are relatively few studies looking at postoperative strategies for managing pain in prosthetic surgery with follow-up past the immediate hospitalization. This review assess the various strategies employed for managing pain following penile implantation through the lens of the current state of the opioid crisis, thus examining how urologists can responsibly treat pain without contributing to the growing threat of opioid addiction.

Risk Factors for Postoperative Fever and Systemic Inflammatory Response Syndrome After Ureteroscopy for Stone Disease.

Introduction: Infectious complications after ureteroscopy (URS) for stone disease lead to emergency department visits, hospitalizations, and other costly health care utilization. The objective of our study was to identify risk factors for postoperative fever (POF) and systemic inflammatory response syndrome (SIRS) after URS for stone disease. Materials and Methods: We performed a retrospective cohort study on 2746 patients who underwent 3298 URS for stone disease at Geisinger from 2008 to 2016. A univariate analysis tested the associations between candidate demographic, preoperative, and intraoperative predictors and the primary outcome of POF (temperature >100.4°F) or SIRS. Variables with a p-value of <0.05 on univariate comparisons were entered into a random-effects logistic regression model. The final model used backward elimination random-effects logistic regression to identify predictors most predictive of POF/SIRS. Results: Overall, 229 (6.9%) of 3298 URS had POF/SIRS. On univariate analysis, individuals with POF/SIRS were older, had higher mean body mass index, higher Charlson Comorbidity Index (CCI), bilateral and larger stones, stone location in the kidney, positive preoperative urine culture, pre-stented, and longer surgical times. In the final model, female gender (adjusted odds ratio [OR] 1.6, 95% confidence interval [CI] 1.19-2.15), surgical time (adjusted OR 1.01, 95% CI 1.0-1.01), CCI ≥2 (adjusted OR 1.86, 95% CI 1.29-2.67), and positive preoperative urine culture (adjusted OR 1.53, 95% CI 1.06-2.22) were the most significant predictors of POF/SIRS. Conclusions: Female gender, longer surgical time, medical complexity, and positive preoperative urine culture are associated with POF/SIRS after URS. These data may be used to identify and counsel high-risk individuals.

External Validation of Contact Surface Area as a Predictor of Postoperative Renal Function in Patients Undergoing Partial Nephrectomy.

PURPOSE: We sought to externally validate a mathematical formula for tumor contact surface area as a predictor of postoperative renal function in patients undergoing partial nephrectomy for renal cell carcinoma. MATERIALS AND METHODS: We queried a prospectively maintained kidney cancer database for patients who underwent partial nephrectomy between 2014 and 2016. Contact surface area was calculated using data obtained from preoperative cross-sectional imaging. The correlation between contact surface area and perioperative variables was examined. The correlation between postoperative renal functional outcomes, contact surface area and the R.E.N.A.L. (radius, exophytic/endophytic properties, nearness of tumor to collecting system or sinus, anterior/posterior, location relative to polar lines and tumor touches main renal artery or vein) nephrometry score was also assessed. RESULTS: A total of 257 patients who underwent partial nephrectomy had sufficient data to enter the study. Median contact surface area was 14.5 cm2 (IQR 6.2-36) and the median nephrometry score was 9 (IQR 7-10). Spearman correlation analysis showed that contact surface area correlated with estimated blood loss (rs = 0.42, p <0.001), length of stay (rs = 0.18, p = 0.005), and percent and absolute change in the estimated glomerular filtration rate (rs = -0.77 and -0.78, respectively, each p <0.001). On multivariable analysis contact surface area and nephrometry score were independent predictors of the absolute change in the estimated glomerular filtration rate (each p <0.001). ROC curve analysis revealed that contact surface area was a better predictor of a greater than 20% postoperative decline in the estimated glomerular filtration rate compared with the nephrometry score (AUC 0.94 vs 0.80). CONCLUSIONS: Contact surface area correlated with the change in postoperative renal function after partial nephrectomy. It can be used in conjunction with the nephrometry score to counsel patients about the risk of renal functional decline after partial nephrectomy.

SPG7 Is an Essential and Conserved Component of the Mitochondrial Permeability Transition Pore.

Mitochondrial permeability transition is a phenomenon in which the mitochondrial permeability transition pore (PTP) abruptly opens, resulting in mitochondrial membrane potential (ΔΨm) dissipation, loss of ATP production, and cell death. Several genetic candidates have been proposed to form the PTP complex, however, the core component is unknown. We identified a necessary and conserved role for spastic paraplegia 7 (SPG7) in Ca(2+)- and ROS-induced PTP opening using RNAi-based screening. Loss of SPG7 resulted in higher mitochondrial Ca(2+) retention, similar to cyclophilin D (CypD, PPIF) knockdown with sustained ΔΨm during both Ca(2+) and ROS stress. Biochemical analyses revealed that the PTP is a heterooligomeric complex composed of VDAC, SPG7, and CypD. Silencing or disruption of SPG7-CypD binding prevented Ca(2+)- and ROS-induced ΔΨm depolarization and cell death. This study identifies an ubiquitously expressed IMM integral protein, SPG7, as a core component of the PTP at the OMM and IMM contact site.

Molecular mechanisms orchestrating the stem cell response to translational scaffolds.

A 2013 Perspective in Science titled "Deconstructing Dimensionality" noted the importance of fiber morphology on cell phenotype, concluding with the statement "Identifying the mechanisms by which cells assess the nature of their environment will advance basic cell biology and facilitate the development of synthetic matrices for specific tissue engineering applications." Nanofibers have revolutionized scaffold-based approaches for musculoskeletal tissues; demonstrating surprising efficacy over promoting mesenchymal stem cell, MSC, differentiation down multiple musculoskeletal lineages. Understanding the fundamental mechanisms involved will allow the future design of nanofiber-based scaffolds to target a lineage with specificity. This article focuses on how three geometry sensors: focal adhesions, membrane associated vesicle stabilizing and trafficking proteins, and adherens junctions; potentially regulate MSC lineage commitment in response to bio-instructive nanofibers.

Osteoinductive biomaterial geometries for bone regenerative engineering.

Worldwide, more than 2.2 million patients undergo bone graft procedures annually. In each of these procedures an interface is formed between the host tissue and the graft material. Synthetic implants exhibit an interface with the host tissue and the formation of a homogenous interface consisting of bone and void of intervening soft tissue is desired (osseointegration); recent developments have highlighted the benefit of incorporating nanostructures at that interface. Autograft and allograft bone are frequently used for bone loss, nonunion fractures, and spinal fusions; however, both are plagued with complications either due to supply or inadequate graft properties. In contrast to bone tissue engineering, which uses a top-down approach to repair bone defects, bone regenerative engineering uses a bottom-up approach focused on strategies incorporating stem cells, biomaterials, and growth factors alone or in combination to generate or regenerate bone tissue. Early constructs developed for bone regenerative engineering utilized polymeric microstructures, presenting surface features with characteristic dimensions similar to that of a cell (1µm - 1000µm). These microstructures were typically biodegradable and demonstrated an excellent ability to match the mechanics of native bone tissue. They were also osteoconductive-capable of promoting osteoblast growth. On the other hand, the osteoinductive abilities of these microstructures were lacking. Osteoinduction, or the ability to promote the progression of a preosteoblastic cell to a mature osteoblast, historically was achieved in two ways: via the addition of nanoscale ceramics to the microstructures or via an external stimulus such as the addition of bone morphogenetic proteins (BMPs). More recent developments in bone regenerative engineering have utilized polymeric nanostructures (less than 1µm) with characteristic dimensions an order of magnitude or more less than that of a cell to stimulate and drive an osteoinductive response in the absence of growth factors. Despite strong literature evidence supporting the nanostructures' ability to be both osteoconductive and osteoinductive, there is still disparity regarding how nanostructures regulate the progression towards an osteoblastic phenotype. This review will explore unique micro- and nano-architectures, how they initiate osteoinductive signals through pathways similar to BMPs, and how these unique geometries can be translated to the clinic.