Epididymal Cyst Lesions Are Not Associated With Impaired Semen Parameters Among Men Presenting for Fertility Evaluation.

PURPOSE: Epididymal cyst lesions (ECLs) include both spermatoceles and epididymal cysts and are often incidentally found on physical exam or scrotal US (SUS). We aimed to determine the association of ECLs and semen parameters among men presenting for fertility evaluation. MATERIALS AND METHODS: We reviewed men at our institution who had at least 1 semen analysis and SUS available for review between 2002 and 2022. SUS data included testicular measurements, presence or absence of subclinical varicocele, and size and laterality of ECL, if present. Demographic and clinical information including serum testosterone and follicle-stimulating hormone and semen parameters were compared between men with and without ECLs. RESULTS: Among 861 men, 164 (19%) had unilateral right ECL (median 4 mm, interquartile range 3-8 mm), 189 (22%) had unilateral left ECL (median 4 mm, interquartile range 3-9 mm), and 113 (13%) had bilateral ECL. Patients with ECLs were significantly older than men without ECLs at the time of evaluation but had no statistically significant difference in semen volume, sperm concentration, sperm motility, sperm morphology, total motile sperm count, or serum hormonal values. Analysis of men with unilateral and bilateral ECLs showed that ECL size and laterality did not significantly correlate with any semen parameter evaluated. CONCLUSIONS: We found no association between ECLs and semen parameters. Patients should be counseled toward conservative management with observation for asymptomatic ECLs in the setting of fertility evaluation.

Methyl-CpG Binding Protein 2 Regulates Microglia and Macrophage Gene Expression in Response to Inflammatory Stimuli.

Mutations in MECP2, encoding the epigenetic regulator methyl-CpG-binding protein 2, are the predominant cause of Rett syndrome, a disease characterized by both neurological symptoms and systemic abnormalities. Microglial dysfunction is thought to contribute to disease pathogenesis, and here we found microglia become activated and subsequently lost with disease progression in Mecp2-null mice. Mecp2 was found to be expressed in peripheral macrophage and monocyte populations, several of which also became depleted in Mecp2-null mice. RNA-seq revealed increased expression of glucocorticoid- and hypoxia-induced transcripts in Mecp2-deficient microglia and peritoneal macrophages. Furthermore, Mecp2 was found to regulate inflammatory gene transcription in response to TNF stimulation. Postnatal re-expression of Mecp2 using Cx3cr1(creER) increased the lifespan of otherwise Mecp2-null mice. These data suggest that Mecp2 regulates microglia and macrophage responsiveness to environmental stimuli to promote homeostasis. Dysfunction of tissue-resident macrophages might contribute to the systemic pathologies observed in Rett syndrome.

Utilizing computed tomography-based renal parenchymal volumes to calculate split renal function in patients with ureteral stricture disease.

PURPOSE: Evaluation of split renal function (SRF) is critical for guiding surgical treatment decisions for patients with ureteral stricture disease (USD). We aimed to determine whether computed tomography (CT)-based renal parenchymal volumes may be used to predict SRF in patients with USD. METHODS: We retrospectively reviewed all patients undergoing surgical management for USD at a single institution from October 2021 to January 2024. Patients who had preoperative nuclear medicine scan (NMS) and CT scan with intravenous contrast that were obtained within six weeks of each other were included. Interval between NMS and CT could be longer if the affected renal unit was drained with ureteral stent and/or percutaneous nephrostomy. Volume measurements were obtained using the 3D Region of Interest (ROI) Tool on Visage®7 Enterprise Imaging Platform (Visage Inc., San Diego, USA) by two investigators that were blinded to NMS derived SRF. Intraclass correlation coefficient (ICC) was used to assess consistency between investigators. Predictive accuracy was assessed using Pearson correlation coefficient (r) and linear regression. RESULTS: 40 of 160 patients met inclusion criteria. There was excellent reliability in calculating renal parenchymal volume between raters (ICC = 0.990). There was a strong linear correlation between estimated CT SRF and NMS SRF (r = 0.912, p < 0.00001). A linear regression model found RObservedSRF = -0.013 + 1.015(REstimatedSRF), with r2 = 0.832. CONCLUSION: CT-derived parenchymal volume analysis may be used to estimate SRF in patients with USD. This may obviate the need to obtain preoperative renal scans for SRF measurement in selected patients when assessing surgical management options.

Development of a Patient-Reported Outcome Measure for Patients with Ureteral Stricture Disease.

OBJECTIVES: To develop a patient-reported outcome measure using qualitative patient-centered methods and expert opinion to quantify the impact of ureteral stricture disease and its management. METHODS: Patients undergoing robotic ureteral reconstruction for ureteral stricture disease between 9/2021-4/2023 were enrolled. A novel patient-reported outcome was developed in four steps: 1) Semi-structured concept elicitation interviews to evaluate the physical, mental, and social effects of ureteral stricture disease; 2) Item generation based on themes identified in the interview transcripts, existing patient-reported outcomes on health-related QOL, and expert opinion; 3) Feedback on the generated items from a panel of external clinicians with high surgical volume for ureteral stricture disease; and 4) Cognitive interviews assessing patient comprehension and relevance. RESULTS: We conducted 14 semi-structured concept-elicitation interviews. After qualitative analysis of these interviews, we generated a 13-item instrument: 8 items assessed symptoms, 4 items assessed QOL, and 1 item assessed patient-perceived treatment success. Expert input supported the content of the patient-reported outcome measure and guided minor adjustments. Two rounds of cognitive interviews were conducted. The first round included 6 patients, and the patient-reported outcome measure was revised according to patient feedback. The second round included 4 patients, and no additional revisions were made based on the second round. CONCLUSIONS: We utilized qualitative patient-centered methods and expert opinion to develop a patient reported outcome measure to assess outcomes in patients undergoing surgery for ureteral stricture disease.

A review of complications after ureteral reconstruction.

Objective: This study aimed to provide a comprehensive overview of the complications unique to ureteral reconstruction in adults, emphasizing their presentation, diagnosis, and management in the treatment of ureteral structure disease. Methods: This review involves an in-depth analysis of existing literature and case studies pertaining to ureteral reconstruction, with a focus on examining the range of complications that can arise post-surgery. Special attention is given to the presentation of each complication, the diagnostic process involved, and the subsequent management strategies. Results: Ureteral reconstruction can treat ureteral stricture disease with low morbidity; however, complications, although uncommon, can have severe consequences. The most notable complications include urinary extravasation, stricture recurrence, urinary tract infections, compartment syndrome, symptomatic vesicoureteral reflux, and Boari flap necrosis. Each complication presents unique diagnostic challenges and requires specific management approaches. Conclusion: Ureteral reconstruction is a highly effective treatment for ureteral stricture disease. Having a strong understanding of the potential complications that patients may experience following ureteral reconstruction is not only critical to adequately counsel patients but also facilitate prompt diagnosis and management of complications when they arise.

Cholinergic Basal Forebrain Connectivity to the Basolateral Amygdala Modulates Food Intake.

Obesity results from excessive caloric input associated with overeating and presents a major public health challenge. The hypothalamus has received significant attention for its role in governing feeding behavior and body weight homeostasis. However, extrahypothalamic brain circuits also regulate appetite and consumption by altering sensory perception, motivation, and reward. We recently discovered a population of basal forebrain cholinergic (BFc) neurons that regulate appetite suppression. Through viral tracing methods in the mouse model, we found that BFc neurons densely innervate the basolateral amygdala (BLA), a limbic structure involved in motivated behaviors. Using channelrhodopsin-assisted circuit mapping, we identified cholinergic responses in BLA neurons following BFc circuit manipulations. Furthermore, in vivo acetylcholine sensor and genetically encoded calcium indicator imaging within the BLA (using GACh3 and GCaMP, respectively) revealed selective response patterns of activity during feeding. Finally, through optogenetic manipulations in vivo, we found that increased cholinergic signaling from the BFc to the BLA suppresses appetite and food intake. Together, these data support a model in which cholinergic signaling from the BFc to the BLA directly influences appetite and feeding behavior.

Risk factors and reasons for reoperation after radical cystectomy.

PURPOSE: Reoperation after radical cystectomy (RC) is common but the types of reoperation after RC and associated risk factors have not been fully characterized. Here, we provide a detailed, contemporary account of the factors that drive surgical reoperation within the first 30-days after surgery, identify at risk patient populations, and describe common reoperations. MATERIALS AND METHODS: The American College of Surgeons National Surgical Quality Improvement Program database (2012-2017) was analyzed to identify 30-day reoperation rates after RC. Captured variables included demographic, preoperative, operative, and postoperative characteristics. Postoperative characteristics included complications, including types of reoperation, length of stay, unplanned readmissions, and discharge destination. Pearson chi-squared and multivariable logistic regression models were used for analysis. RESULTS: A total of 10,848 patients underwent RC and there were 633 (5.84%) unplanned reoperations. On multivariable logistic regression, patient factors associated with increased risk of reoperation included longer operative times at index procedure (>90th percentile operative time) (OR1.41 [1.08-1.83], P = 0.02), smoking (OR1.34 [1.11-1.63], P < 0.01), obesity (BMI≥30) (OR 1.29 [1.04-1.60], P = 0.02) and chronic obstructive pulmonary disease (OR1.74 [1.36-2.3], P < 0.01). Other significant factors included clinically significant hypertension, perioperative blood transfusion, and male sex. The most common reoperation procedures were those performed on the gastrointestinal tract, accounting for 60.59% (349) of all reoperations, followed by skin/subcutaneous procedures 14.76% (85), followed by Genitourinary procedures at 8.16% (47). Patients who underwent reoperation were at higher risk for readmission, discharge to a facility, and death (P < 0.01). CONCLUSION: Reoperation after RC is associated with approximately 5% rate of reoperation within 30 days of surgery. The most common reason for reoperation was related to the gastrointestinal tract, accounting for more than 60% of all reoperations. Risk factors for reoperation included longer surgical times, smoking, obesity, chronic obstructive pulmonary disease, perioperative blood transfusion, and clinically significant hypertension. Knowledge of these factors can aid in operative planning and counseling and lead to possible strategies to reduce reoperations in the early perioperative setting.

Peripherally derived macrophages can engraft the brain independent of irradiation and maintain an identity distinct from microglia.

Peripherally derived macrophages infiltrate the brain after bone marrow transplantation and during central nervous system (CNS) inflammation. It was initially suggested that these engrafting cells were newly derived microglia and that irradiation was essential for engraftment to occur. However, it remains unclear whether brain-engrafting macrophages (beMφs) acquire a unique phenotype in the brain, whether long-term engraftment may occur without irradiation, and whether brain function is affected by the engrafted cells. In this study, we demonstrate that chronic, partial microglia depletion is sufficient for beMφs to populate the niche and that the presence of beMφs does not alter behavior. Furthermore, beMφs maintain a unique functional and transcriptional identity as compared with microglia. Overall, this study establishes beMφs as a unique CNS cell type and demonstrates that therapeutic engraftment of beMφs may be possible with irradiation-free conditioning regimens.

Evaluation of Acellular Dermal Matrix Efficacy in Prosthesis-Based Breast Reconstruction.

BACKGROUND: Although many studies have examined the safety of acellular dermal matrix in immediate prosthetic breast reconstruction, few studies have evaluated efficacy. This study examined initial tissue expander fill volume as a marker of efficacy, comparing patients after staged prosthetic breast reconstruction assisted with acellular dermal matrix versus breast reconstruction not assisted with acellular dermal matrix. Number of fill visits and time interval to implant exchange were examined as secondary endpoints. METHODS: An institutional review board-approved retrospective chart review was conducted to identify consecutive staged prosthetic reconstruction cases over 12 years. RESULTS: Mean initial tissue expander fill volume was significantly higher in the acellular dermal matrix group compared with the non-acellular dermal matrix group (180.8 ± 150.0 versus 45.8 ± 74.4; p = 0.00). Normalizing for final implant size, the acellular dermal matrix group exhibited significantly higher perioperative fill (0.33 ± 0.24 versus 0.11 ± 0.16; p = 0.00). A collinear trend was observed between acellular dermal matrix use and direct-to-implant reconstruction procedures during the study period. CONCLUSIONS: These results suggest that acellular dermal matrix use is more efficacious in achieving greater initial fill volume, fewer visits for expansion, and a shorter time interval to implant exchange compared with non-acellular dermal matrix procedures. The authors also describe a collinear relationship between acellular dermal matrix use and transition to direct-to-implant procedures at their institution. This work serves as a framework for future studies evaluating acellular dermal matrix efficacy, and guides innovation of biomaterials to support breast reconstruction. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.