Diagnosis and Treatment of Early-Stage Testicular Cancer: AUA Guideline Amendment 2023.

PURPOSE: The purpose of this American Urological Association (AUA) guideline amendment is to provide a useful reference on the effective evidence-based treatment strategies for early-stage testicular cancer. METHODOLOGY/METHODS: The original methodology protocol included searches of PubMed®, Embase®, and the Cochrane Central Register of Controlled Trials (CENTRAL) from January 1980 through August 2018. The search strategy used medical subject heading (MeSH) terms and key words relevant to the diagnosis and treatment of early-stage testicular cancer. The searches conducted for the update presented herein utilized the same methodological protocol to capture literature published through March 2023. When sufficient evidence existed, the body of evidence was assigned a strength rating of A (high), B (moderate), or C (low) for support of Strong, Moderate, or Conditional Recommendations. In the absence of sufficient evidence, additional information is provided as Clinical Principles and Expert Opinions. RESULTS: Updates were made to statements on imaging, seminoma management, non-seminoma management, surveillance for stage I testicular cancer, and additional survivorship. Further revisions were made to the methodology and reference sections as appropriate. CONCLUSIONS: This guideline seeks to improve clinicians' ability to evaluate and treat patients with early-stage testicular cancer based on currently available evidence. Future studies will be essential to further support or refine these statements to improve patient care.

The effect of cisplatin-based neoadjuvant chemotherapy on the renal function of patients undergoing radical cystectomy.

INTRODUCTION: Cisplatin-based neoadjuvant chemotherapy (NAC) is the standard of care for patients with muscle-invasive bladder cancer (MIBC) undergoing radical cystectomy (RC). Cisplatin, however, can induce renal toxicity. Furthermore, RC is an independent risk factor for renal injury, with decreases in estimated glomerular filtration rate (eGFR) of up to 6 mL/min/1.73 m2 reported at one year postoperatively. Our objective was to evaluate the effect of cisplatin-based NAC and RC on the renal function of patients undergoing both. METHODS: We analyzed a multicenter database of patients with MIBC, all of whom received cisplatin-based NAC prior to RC. eGFR values were collected at time points T1 (before NAC), T2 (after NAC but before RC), and T3 (one year post-RC). eGFR and proportion of patients with eGFR <60 ml/min/1.73m2 (chronic kidney disease [CKD] stage ≥3) were compared between these time points. As all patients in this dataset had received NAC, we identified a retrospective cohort of patients from one institution who had undergone RC during the same time period without NAC for context. RESULTS: We identified 234 patients with available renal function data. From T1 to T3, there was a mean decline in eGFR of 17% (13 mL/min/1.73 m2) in the NAC cohort and an increase in proportion of patients with stage ≥3 CKD from 27% to 50%. The parallel cohort of patients who did not receive NAC was comprised of 236 patients. The mean baseline eGFR in this cohort was lower than in the NAC cohort (66 vs. 75 mL/min/1.73 m2). The mean eGFR decline in this non-NAC cohort from T1 to T3 was 6% (4 mL/min/1.73 m2), and the proportion of those with stage ≥3 CKD increased from 37% to 51%. CONCLUSIONS: Administration of NAC prior to RC was associated with a 17% decline in eGFR and a nearly doubled incidence of stage ≥3 CKD at one year after RC. Patients who underwent RC without NAC had a higher rate of stage ≥3 CKD at baseline but appeared to have less renal function loss at one year.

Impact of Maximal Transurethral Resection on Pathological Outcomes at Cystectomy in a Large, Multi-institutional Cohort.

PURPOSE: While the presence of residual disease at the time of radical cystectomy for bladder cancer is an established prognostic indicator, controversy remains regarding the importance of maximal transurethral resection prior to neoadjuvant chemotherapy. We characterized the influence of maximal transurethral resection on pathological and survival outcomes using a large, multi-institutional cohort. MATERIALS AND METHODS: We identified 785 patients from a multi-institutional cohort undergoing radical cystectomy for muscle-invasive bladder cancer after neoadjuvant chemotherapy. We employed bivariate comparisons and stratified multivariable models to quantify the effect of maximal transurethral resection on pathological findings at cystectomy and survival. RESULTS: Of 785 patients, 579 (74%) underwent maximal transurethral resection. Incomplete transurethral resection was more frequent in patients with more advanced clinical tumor (cT) and nodal (cN) stage (P < .001 and P < .01, respectively), with more advanced ypT stage at cystectomy and higher rates of positive surgical margins (P < .01 and P < .05, respectively). In multivariable models, maximal transurethral resection was associated with downstaging at cystectomy (adjusted odds ratio 1.6, 95% CI 1.1-2.5). In Cox proportional hazards analysis, maximal transurethral resection was not associated with overall survival (adjusted HR 0.8, 95% CI 0.6-1.1). CONCLUSIONS: In patients undergoing transurethral resection for muscle-invasive bladder cancer prior to neoadjuvant chemotherapy, maximal resection may improve pathological response at cystectomy. However, the ultimate effects on long-term survival and oncologic outcomes warrant further investigation.

Ocular Cicatricial Pemphigoid With IgM-Positive Biopsy.

PURPOSE: The aim of this study was to investigate the prevalence of IgM along the basement membrane zone (BMZ) of patients with ocular cicatricial pemphigoid (OCP) and the outcomes of these patients with immunomodulatory therapy. METHODS: This study is a retrospective chart review of patients with conjunctival biopsy-proven OCP. Clinical data, including the presence of linear IgM deposition along the BMZ on either direct immunofluorescence or avidin-biotin complex immunohistochemistry, were recorded. Response to IMT was also recorded. RESULTS: A total of 817 patients with documented conjunctival biopsies were identified, with 93 (11.4%) positive for OCP with linear IgM deposition along the BMZ. Forty-six patients with sufficient follow-up were evaluated for clinical outcomes, with 35 (76.1%) able to achieve durable remission an average of 24.3 months after initiation of IMT. Most of these patients, 82.9%, were able to achieve durable remission with first-line antimetabolite therapy. Three patients were identified with solely IgM-positive conjunctival biopsies. CONCLUSIONS: Our study suggests that IgM positivity is seen in a minority of patients with OCP and that outcomes are comparable for these patients to the general OCP patient population.

A peculiar case of aqueous misdirection from a pseudophakic secluded pupil in a patient with chronic angle closure glaucoma.

Purpose: To explore the course of a pseudophakic and pseudoiridic 61-year-old man with a history of open angle glaucoma in his right eye who developed a sub-totally secluded pupil then later presented with angle closure, a significant pressure spike, and a marked myopic refractive shift, consistent with aqueous misdirection. Observations: Goniosynechialysis, surgical removal of much of the native peripheral iris, and zonulohyaloidectomy led to a return to his prior refraction and improve intraocular pressure (IOP) control. Conclusions and Importance: This case demonstrates that a diagnosis of aqueous misdirection should not be disregarded in the presence of a prior vitrectomy and that aqueous misdirection should be strongly considered in cases of elevated IOP with a patent peripheral iridotomy, myopic shift and angle narrowing.

Substance use and victimization experiences among college students in Spain.

OBJECTIVE: We examined relationships between different types and patterns of substance use and victimization experiences. PARTICIPANTS: College students from two universities in Spain completed an online, cross-sectional survey. METHOD: A series of tetrachoric correlations were estimated to examine the bivariate associations between different types of substances and victimization experiences. Regression analyses then examined relationships between patterns of substance use (non-users, mono-users, and poly-users), and victimization. RESULTS: Slightly over half (57.7%) of students reported any form of victimization during the previous year, and most students (87.0%) reported using substances during the last three months. Polysubstance users were more likely than non-users to experience any victimization, as well as multiple forms of victimization. CONCLUSIONS: Findings highlight the importance of differentiating types and patterns of substance use when developing prevention and intervention programs. Implementing intervention strategies that target polysubstance users and decrease substance use could reduce rates of victimization among college students.

Adverse effects of inbreeding on the transgenerational expression of herbivore-induced defense traits in Solanum carolinense.

In addition to directly inducing physical and chemical defenses, herbivory experienced by plants in one generation can influence the expression of defensive traits in offspring. Plant defense phenotypes can be compromised by inbreeding, and there is some evidence that such adverse effects can extend to the transgenerational expression of induced resistance. We explored how the inbreeding status of maternal Solanum carolinense plants influenced the transgenerational effects of herbivory on the defensive traits and herbivore resistance of offspring. Manduca sexta caterpillars were used to damage inbred and outbred S. carolinense maternal plants and cross pollinations were performed to produced seeds from herbivore-damaged and undamaged, inbred and outbred maternal plants. Seeds were grown in the greenhouse to assess offspring defense-related traits (i.e., leaf trichomes, internode spines, volatile organic compounds) and resistance to herbivores. We found that feeding by M. sexta caterpillars on maternal plants had a positive influence on trichome and spine production in offspring and that caterpillar development on offspring of herbivore-damaged maternal plants was delayed relative to that on offspring of undamaged plants. Offspring of inbred maternal plants had reduced spine production, compared to those of outbred maternal plants, and caterpillars performed better on the offspring of inbred plants. Both herbivory and inbreeding in the maternal generation altered volatile emissions of offspring. In general, maternal plant inbreeding dampened transgenerational effects of herbivory on offspring defensive traits and herbivore resistance. Taken together, this study demonstrates that inducible defenses in S. carolinense can persist across generations and that inbreeding compromises transgenerational resistance in S. carolinense.

Oncological Follow-up Strategies for Testicular Germ Cell Tumours: A Narrative Review.

Context: The aim of this review is to describe the proportion of testicular germ cell tumours (tGCTs) with recurrence, and the timing and anatomical sites of relapse across different disease stages and after different treatment options. We summarise published follow-up protocols and discuss current and future developments to personalise follow-up for patients with tGCT. Evidence acquisition: A systematic literature search was conducted and current guidelines and selected institutional follow-up protocols were reviewed. Evidence synthesis: Of 302 publications, we screened 68 full texts and included 29 studies; 22 of these were retrospective and seven were prospective in nature, contributing data for 20 570 patients. The number of patients included per study ranged from 119 to 2483. We compared the guideline follow-up protocols of the European Society for Medical Oncology, European Association of Urology, National Comprehensive Cancer Network, and American Urological Association, as well as institutional follow-up protocols. The protocols differed in terms of the number, time points, and type of follow-up investigations. Conclusions: Future research should assess how tGCT can be followed to ensure high adherence, define the role of miR-371a-3p microRNA during follow-up, and develop follow-up protocols after curative treatment in the metastatic setting. Patient summary: In this review of follow-up protocols for men with testis cancer, we observed different recommendations and discuss future research areas to improve follow-up for these patients.

Multicenter evaluation of neoadjuvant and induction gemcitabine-carboplatin versus gemcitabine-cisplatin followed by radical cystectomy for muscle-invasive bladder cancer.

PURPOSE: Cisplatin-based chemotherapy followed by radical cystectomy (RC) is recommended in patients with muscle-invasive bladder cancer (MIBC). However, up to 50% of patients are cisplatin ineligible. The aim of this study was to compare clinical outcomes after ≥ 3 cycles of preoperative gemcitabine-carboplatin (gem-carbo) versus gemcitabine-cisplatin (gem-cis). METHODS: We identified 1865 patients treated at 19 centers between 2000 and 2013. Patients were included if they had received ≥ 3 cycles of neoadjuvant (cT2-4aN0M0) or induction (cTanyN + M0) gem-carbo or gem-cis followed by RC. RESULTS: We included 747 patients treated with gem-carbo (n = 147) or gem-cis (n = 600). Patients treated with gem-carbo had a higher Charlson Comorbidity Index (p = 0.016) and more clinically node-positive disease (32% versus 20%; p = 0.013). The complete pathological response (pCR; ypT0N0) rate did not significantly differ between gem-carbo and gem-cis (20.7% versus 22.1%; p = 0.73). Chemotherapeutic regimen was not significantly associated with pCR (OR 0.99 [95%CI 0.61-1.59]; p = 0.96), overall survival (OS) (HR 1.20 [95%CI 0.85-1.67]; p = 0.31), or cancer-specific survival (CSS) (HR 1.35 [95%CI 0.93-1.96]; p = 0.11). Median OS of patients treated with gem-carbo and gem-cis was 28.6 months (95%CI 18.1-39.1) and 45.1 months (95%CI 32.7-57.6) (p = 0.18), respectively. Median CSS of patients treated with gem-carbo and gem-cis was 28.8 months (95%CI 9.8-47.8) and 71.0 months (95%CI median not reached) (p = 0.02), respectively. Subanalyses of the neoadjuvant and induction setting did not show significant survival differences. CONCLUSION: Our results show that a subset of cisplatin-ineligible patients with MIBC achieve pCR on gem-carbo and that survival outcomes seem comparable to gem-cis provided patients are able to receive ≥ 3 cycles and undergo RC.

How Engineers and Roadside Vegetation Managers Maintain Roadside Vegetation in Iowa, USA.

Recently the value of roadside vegetation as habitat for pollinators has gained increased attention, particularly in areas dominated by agriculture where there is little native vegetation available. However, many factors, including safety, cost, public perception, erosion control, and weedy plants must be considered when managing roadside vegetation. Although their decisions influence thousands of hectares of public rights-of-way, how engineers and roadside managers maintain roadside vegetation has been the subject of little research. In this study, we surveyed county engineers and roadside managers who manage vegetation along secondary roads in Iowa, USA to assess how they maintain roadside vegetation. Some counties employ roadside managers, who often have an environmental sciences background, to implement the on-the-ground management of roadside vegetation, while some counties use other staff. Compared to engineers, roadside managers more strongly agreed that using the ecological principles of integrated roadside vegetation management (IRVM) provided environmental benefits. Engineers in counties with a roadside manager more strongly agreed that IRVM practices reduce the spread of invasive species and provide attractive roadsides. Both engineers and roadside managers mentioned challenges to managing roadside vegetation, including interference with some native plantings by adjacent landowners, and ranked safety and soil erosion concerns as the highest priorities when making decisions. Four in ten roadside managers said their counties had protected native plant community remnants on secondary roadsides. Our findings can inform conservation outreach efforts to those responsible for managing roadside vegetation, and emphasize the importance of addressing safety and soil erosion concerns in roadside research and communications.

Identifying the Optimal Number of Neoadjuvant Chemotherapy Cycles in Patients with Muscle Invasive Bladder Cancer.

PURPOSE: We investigated the pathological response rates and survival associated with 3 vs 4 cycles of cisplatin-based neoadjuvant chemotherapy (NAC) in patients with cT2-4N0M0 muscle invasive bladder cancer. MATERIALS AND METHODS: In this cohort study we analyzed clinical data of 828 patients treated with NAC and radical cystectomy between 2000 and 2020. A total of 384 and 444 patients were treated with 3 and 4 cycles of NAC, respectively. Pathological objective response (pOR; ypT0-Ta-Tis-T1 N0), pathological complete response (pCR; ypT0 N0), cancer-specific survival and overall survival were investigated. RESULTS: pOR and pCR were achieved in 378 (45%; 95% CI 42, 49) and 207 (25%; 95% CI 22, 28) patients, respectively. Patients treated with 4 cycles of NAC had higher pOR (49% vs 42%, p=0.03) and pCR (28% vs 21%, p=0.02) rates compared to those treated with 3 cycles. This effect was confirmed on multivariable logistic regression analysis (pOR OR 1.46 p=0.008, pCR OR 1.57, p=0.007). On multivariable Cox regression analysis, 4 cycles of NAC were significantly associated with overall survival (HR 0.68; 95% CI 0.49, 0.94; p=0.02) but not with cancer-specific survival (HR 0.72; 95% CI 0.50, 1.04; p=0.08). CONCLUSIONS: Four cycles of NAC achieved better pathological response and survival compared to 3 cycles. These findings may aid clinicians in counseling patients and serve as a benchmark for prospective trials. Prospective validation of these findings and assessment of cumulative toxicity derived from an increased number of cycles are needed.

Association of age with response to preoperative chemotherapy in patients with muscle-invasive bladder cancer.

PURPOSE: To assess the association of patient age with response to preoperative chemotherapy in patients with muscle-invasive bladder cancer (MIBC). MATERIALS AND METHODS: We analyzed data from 1105 patients with MIBC. Patients age was evaluated as continuous variable and stratified in quartiles. Pathologic objective response (pOR; ypT0-Ta-Tis-T1N0) and pathologic complete response (pCR; ypT0N0), as well survival outcomes were assessed. We used data of 395 patients from The Cancer Genome Atlas (TCGA) to investigate the prevalence of TCGA molecular subtypes and DNA damage repair (DDR) gene alterations according to patient age. RESULTS: pOR was achieved in 40% of patients. There was no difference in distribution of pOR or pCR between age quartiles. On univariable logistic regression analysis, patient age was not associated with pOR or pCR when evaluated as continuous variables or stratified in quartiles (all p > 0.3). Median follow-up was 18 months (IQR 6-37). On Cox regression and competing risk regression analyses, age was not associated with survival outcomes (all p > 0.05). In the TCGA cohort, patient with age ≤ 60 years has 7% less DDR gene mutations (p = 0.59). We found higher age distribution in patients with luminal (p < 0.001) and luminal infiltrated (p = 0.002) compared to those with luminal papillary subtype. CONCLUSIONS: While younger patients may have less mutational tumor burden, our analysis failed to show an association of age with response to preoperative chemotherapy or survival outcomes. Therefore, the use of preoperative chemotherapy should be considered regardless of patient age.

Treatment of Noninfectious Retinal Vasculitis Using Subcutaneous Repository Corticotropin Injection.

PURPOSE: To show whether subcutaneous repository corticotropin injection (RCI, Acthar® Gel, a repository corticotropin injection, can be an effective potential therapeutic agent for noninfectious retinal vasculitis. METHODS: Patients with active retinal vasculitis were followed with serial ultra-wide-field fluorescein angiograms and treated with 80 units of subcutaneous repository corticotropin injection twice weekly. RESULTS: Primary outcome of ≥ 50% improvement in response level (RL) for retinal vasculitis and percent improvement in retinal vasculitis severity scoring (RVSS) by more than one quartile ( ≥ 25%) at week 12 was met in 15 and 16 of the 30 total eyes, respectively, including 1 eye with severe retinal vasculitis in each group. Complete resolution of retinal vasculitis was seen in seven eyes with a mean time of 17.1 weeks. Intraocular pressure elevation requiring therapy and cataract progression were noted in two and three eyes, respectively. One patient stopped medication due to side effects (injection site reaction). CONCLUSION: Repository corticotropin injection was well-tolerated overall. Repository corticotropin injection may be an effective therapeutic agent in the treatment of noninfectious retinal vasculitis.

Local Decision-makers' Perspectives on Roadside Revegetation and Management in Iowa, USA.

Environmental practitioners must understand those they collaborate with to implement programs that are both socially and ecologically effective. Practitioners who understand decision-makers' perspectives are better able to collaborate to lower political, financial, and cultural obstacles. In this study, we surveyed decision-makers involved with a voluntary environmental program in Iowa, USA. Iowa counties can choose to manage their roadside vegetation using an ecological approach, called integrated roadside vegetation management. Key decision-makers who decide whether a county has a roadside program are the county board of supervisors and the county conservation board. We used a mixed-mode design to survey the conservation board directors and chairs of the board of supervisors in each county. Our main goals were to understand the decision-makers' perceived benefits and barriers to having a roadside program in their counties, as well as the key factors influencing their decisions about roadside vegetation management. Safety, maintenance cost savings, and erosion control were the main factors that influenced decision-making, while pollinators and other wildlife received the least consideration. However, decision-makers in counties with a roadside vegetation manager were more influenced by pollinators and other wildlife compared to their counterparts in counties without a roadside vegetation manager. The main barriers to having a program include a lack of resources or other concerns being a higher priority. Emphasizing safety, cost savings, and erosion control benefits of roadside programs, and identifying ways to lower startup costs may increase buy-in with county decision-makers.

Inbreeding in Solanum carolinense alters floral attractants and rewards and adversely affects pollinator visitation.

PREMISE: Inbreeding depression is well documented in flowering plants and adversely affects a wide range of fitness-related traits. Recent work has begun to explore the effects of inbreeding on ecological interactions among plants and other organisms, including insect herbivores and pathogens. However, the effects of inbreeding on floral traits, floral scents, and pollinator visitation are less well studied. METHODS: Using inbred and outbred maternal families of horsenettle (Solanum carolinense, Solanaceae), we examined the effects of inbreeding on traits associated with pollinator attraction and floral rewards. Specifically, we measured corolla size, counted pollen grains per flower, and analyzed floral volatile emissions via gas chromatography and mass spectrometry. We also examined pollinator visitation to experimental arrays of flowering inbred and outbred plants under field conditions. RESULTS: Compared to those of outbred plants, flowers of inbred plants exhibited reduced corolla size and pollen production, as well as significantly reduced emission of the two most abundant volatile compounds in the floral blend. Furthermore, bumblebees-the main pollinators of horsenettle-discriminated against inbred flowers in the field: bees were more likely to make initial visits to flowers on outbred plants, visited outbred flowers more often overall, and spent more time on outbred flowers. CONCLUSIONS: These results show that inbreeding can (1) alter floral traits that are known to mediate pollinator attraction; (2) reduce the production of floral rewards (pollen is the sole reward in horsenettle); and (3) adversely affect pollinator visitation under field conditions.

Substance Use, Family Functionality, and Mental Health among College Students in Spain.

Mental health symptoms are overrepresented among college students worldwide. The current research investigates the associations among substance use, family functionality, and mental health (depression, anxiety, and stress) among college students in Spain. A total of 828 (59.2% female and 40.8% male) college students from two public universities completed a self-reported online survey that included items on demographic information, substance use (alcohol, tobacco, cannabis, cocaine, prescription sedatives, and recreational sedatives), mental health symptoms (using the DASS-21 questionnaire) and family functionality (using the APGAR questionnaire). College students reporting substance use (especially recreational sedatives) and family dysfunctionality were more likely to exhibit symptoms of depression, anxiety and stress. These findings provide support for the underlying role of substance use and family functionality on mental health symptoms. Treatments targeting depression, anxiety, and stress among college students in Spain should aim to reduce substance use by and increase family support of students.

Neoadjuvant chemotherapy plus radical cystectomy versus radical cystectomy alone in clinical T2 bladder cancer without hydronephrosis.

OBJECTIVES: To assess the efficacy of neoadjuvant chemotherapy (NAC) before radical cystectomy (RC) in a retrospective multicentre cohort of patients with cT2N0M0 bladder cancer (BCa) without preoperative hydronephrosis. PATIENTS AND METHODS: This was a propensity-based analysis of 619 patients. Of these, 316 were treated with NAC followed by RC and 303 with upfront RC. After multiple imputations, inverse probability of treatment weighting (IPTW) was used to account for potential selection bias. Multivariable logistic regression analysis was performed to evaluate the impact of NAC on pathological complete response and downstaging at RC, while IPTW-adjusted Kaplan-Meier curves and Cox regression models were built to evaluate the impact of NAC on overall survival (OS). RESULTS: After IPTW-adjusted analysis, standardised differences between groups were <15%. A complete response (pT0N0) at final pathology was achieved in 94 (30%) patients receiving NAC and nine (3%) undergoing upfront RC. Downstaging to non-muscle-invasive disease (

CRYOPYRIN-ASSOCIATED PERIODIC SYNDROME-ASSOCIATED UVEITIS AND PAPILLITIS.

PURPOSE: To report a case of uveitis and papillitis in a patient with cryopyrin-associated periodic syndrome. METHODS: Case report. A 44-year-old white woman with a long history of inflammatory arthritis, diffuse erythematous rashes and hives, and hearing loss was referred to the Massachusetts Eye Research and Surgery Institution for an evaluation of chronic ocular inflammation. She was diagnosed with bilateral papillitis and uveitis after a comprehensive eye examination, which included dilated fundoscopy, optic nerve ocular coherence tomography, fluorescein angiography, indocyanine green angiography, and B-scan ultrasonography. She was later diagnosed with cryopyrin-associated periodic syndrome, an interleukin-1-driven autoimmune disease, as confirmed by genetic testing. Soon after starting treatment with anakinra, a human interleukin-1 receptor antagonist, she experienced rapid improvement of her ocular and systemic symptoms, including rash, uveitis, and arthritis. RESULTS: Cryopyrin-associated periodic syndrome-associated ocular inflammation in remission with anakinra 100-mg daily subcutaneous injection. CONCLUSION: Anakinra is a very effective treatment for both cryopyrin-associated periodic syndrome and cryopyrin-associated periodic syndrome-associated ocular inflammation.