Induction and maintenance of sequential intravesical gemcitabine/docetaxel for intermediate and high-risk non-muscle invasive bladder cancer with different dosage protocols.

INTRODUCTION: The combination of sequential intravesical gemcitabine and docetaxel (Gem/Doce) chemotherapy has been considered a feasible option for BCG (Bacillus Calmette-Guérin) treatment in non-muscle invasive bladder cancer (NMIBC), gaining popularity during BCG shortage period. We seek to determine the efficacy of the treatment by comparing Gem/Doce induction alone vs induction with maintenance, and to evaluate the treatment outcomes of two different dosage protocols. METHODS: A bi-center retrospective analysis of consecutive patients treated with Gem/Doce for NMIBC between 2018 and 2023 was performed. Baseline characteristics, risk group stratification (AUA 2020 guidelines), pathological, and surveillance reports were collected. Kaplan-Meier survival analysis was performed to detect Recurrence-free survival (RFS). RESULTS: Overall, 83 patients (68 males, 15 females) with a median age of 73 (IQR 66-79), and a median follow-up time of 18 months (IQR 9-25), were included. Forty-one had an intermediate-risk disease (49%) and 42 had a high-risk disease (51%). Thirty-seven patients (45%) had a recurrence; 19 (23%) had a high-grade recurrence. RFS of Gem/Doce induction-only vs induction + maintenance was at 6 months 88% vs 100%, at 12 months 71% vs 97%, at 18 months 57% vs 91%, and at 24 months 31% vs 87%, respectively (log-rank, p < 0.0001). Patients who received 2 g Gemcitabine with Docetaxel had better RFS for all-grade recurrences (log-rank, p = 0.017). However, no difference was found for high-grade recurrences. CONCLUSION: Gem/Doce induction with maintenance resulted in significantly better RFS than induction-only. Combining 2 g gemcitabine with docetaxel resulted in better RFS for all-grade but not for high-grade recurrences. Further prospective trials are necessary to validate our results.

Incidence and management of prostatic urethra recurrence in a cohort of 21 patients who received BCG induction for non-muscle invasive bladder cancer.

PURPOSE: To describe the incidence and management of patients who develop a prostatic urethral (PU) urothelial carcinoma recurrence after Bacillus Calmette-Guerin (BCG) induction for non-muscle invasive bladder cancer (NMIBC). MATERIALS AND METHODS: We performed a retrospective cohort study of all patients who received BCG induction at our institution from 1996 to 2021 (N = 642) for NMIBC. All patients with pathologically confirmed PU involvement following BCG induction with no known PU involvement pre-BCG were included. We describe the presentation, management, and outcomes for PU recurrence. RESULTS: Among the 642 patients, 21 (3.3%) patients had a PU recurrence after BCG induction. 8 (38%) patients received >2 cycles of BCG induction prior to the recurrence. Median time from induction to PU recurrence was 21 months and 12 (57.1%) patients had concurrent bladder recurrence. At the time of their PU recurrence, 14/21 (67%) of patients were deemed BCG Unresponsive. Nearly all (18/21) were high grade, and 10 were stage Tis, 7 Ta, and 3 T1, and 1 T2. 19/21 (90%) patients received bladder sparing treatment: 6 with TURBT and BCG, 6 with TURBT and intravesical chemotherapy, 5 with TURBT only, and 2 did not receive immediate treatment of their PU recurrence due to advanced stage of disease. 2/21 (9.5%) received a radical cystectomy for initial treatment of the post-BCG PU recurrence, of which all were >pT2. Median follow-up time from BCG induction to the patient's last visit was 64.5 months. Following treatment of PU recurrence, 15/18 patients had another recurrence at a median of 5 months: about 47% of recurrences were bladder only and 14% recurred only in the PU as well. About 1 patient received a RC after the second recurrence and was pT2. CONCLUSION: Patients with PU recurrences following intravesical BCG have a high-risk disease phenotype with a significant risk of recurrence. Conservative management may be appropriate for well-selected patients who do not desire a cystoprostatectomy.

Local tree cover predicts mosquito species richness and disease vector presence in a tropical countryside landscape.

Context: Land use change drives both biodiversity loss and zoonotic disease transmission in tropical countryside landscapes. Developing solutions for protecting countryside biodiversity, public health, and livelihoods requires understanding the scales at which habitat characteristics such as land cover shape biodiversity, especially for arthropods that transmit pathogens. Evidence increasingly shows that species richness for many taxa correlates with local tree cover. Objectives: We investigated whether mosquito species richness, community composition, and presence of disease vector species responded to land use and tree cover - and if so, whether at spatial scales similar to other taxa. Methods: We paired a field survey of mosquito communities in agricultural, residential, and forested lands in rural southern Costa Rica with remotely sensed tree cover data. We compared mosquito community responses to tree cover surrounding survey sites measured across scales, and analyzed community responses to land use and environmental gradients. Results: Tree cover was positively correlated with mosquito species richness, and negatively correlated with the presence of the common invasive dengue vector Aedes albopictus, particularly at small spatial scales of 80 - 200m. Land use predicted community composition and Ae. albopictus presence. Environmental gradients of tree cover, temperature, and elevation explained 7% of species turnover among survey sites. Conclusions: The results suggest that preservation and expansion of tree cover at local scales can protect biodiversity for a wide range of taxa, including arthropods, and also confer protection against disease vector occurrence. The identified spatial range of tree cover benefits can inform land management for conservation and public health protection.

Resident Remediation: A National Survey of Urology Program Directors.

OBJECTIVES: To describe formal remediation rates and processes in urology training programs nationally. DESIGN, SETTING, AND PARTICIPANTS: We performed a cross-sectional study by surveying program directors (PDs) through the Society of Academic Urologists. Formal remediation was defined as the process initiated when resident competency deficiencies were significant enough to necessitate documentation and notification of the Graduate Medical Education (GME) office. The primary outcome was the prevalence of urology programs that initiated formal remediation over the past 5 years. Secondary outcomes included reported competency deficiencies and formal remediation processes. RESULTS: Across 148 institutions, 73 (49%) PDs responded to the survey. The majority of PDs (67%, 49/73) stated that at least 1 resident underwent formal remediation over the last 5 years (median 1). "Professionalism" and "Interpersonal and Communication Skills" were the most common competency deficiencies that prompted formal remediation, whereas "Technical Skill" was the least common. While the majority of respondents notified the GME office of residents undergoing remediation, formal remediation plans varied from faculty coaching and mentorship (80%, 39/49) to simulation training (10%, 5/49). Absence of documented faculty feedback on poor performance was the most commonly cited barrier to formal remediation. The majority of PDs reported documentation in a resident's file (81%, 59/73); however, remediation processes differed with only half of PDs reporting that GME offices were routinely involved in creating and overseeing corrective action plans (56%, 41/73). Over the study period, 15% (11/73) of PDs did not promote a resident to the next year of training, and 23% (17/73) of PDs stated "Yes" to graduating a resident who they would not trust to care for a loved one. CONCLUSIONS: Formal remediation among urology residency programs is common, and processes vary across institutions. The most common competency areas prompting remediation were "Professionalism" and "Interpersonal and Communication Skills." Future research should address developing resources to facilitate resident remediation.

Why nature matters: A systematic review of intrinsic, instrumental, and relational values.

In this article, we present results from a literature review of intrinsic, instrumental, and relational values of nature conducted for the Intergovernmental Science-Policy Platform on Biodiversity and Ecosystem Services, as part of the Methodological Assessment of the Diverse Values and Valuations of Nature. We identify the most frequently recurring meanings in the heterogeneous use of different value types and their association with worldviews and other key concepts. From frequent uses, we determine a core meaning for each value type, which is sufficiently inclusive to serve as an umbrella over different understandings in the literature and specific enough to help highlight its difference from the other types of values. Finally, we discuss convergences, overlapping areas, and fuzzy boundaries between different value types to facilitate dialogue, reduce misunderstandings, and improve the methods for valuation of nature's contributions to people, including ecosystem services, to inform policy and direct future research.

Interruptions in bladder cancer care during the COVID-19 public health emergency.

BACKGROUND: Academic and community urology centers participating in a pragmatic clinical trial in non-muscle-invasive bladder cancer completed monthly surveys assessing restrictions in aspects of bladder cancer care due to the COVID-19 Public Health Emergency. Our objective was to describe pandemic-related restrictions on bladder cancer care. METHODS: We invited 32 sites participating in a multicenter pragmatic bladder cancer trial to complete monthly surveys distributed through REDCap beginning in May 2020. These surveys queried sites on whether they were experiencing restrictions in the use of elective surgery, transurethral resection of bladder tumors (TURBT), radical cystectomy, office cystoscopy, and intravesical bacillus Calmette-Guerin (BCG) availability. Responses were collated with descriptive statistics. RESULTS: Of 32 eligible sites, 21 sites had at least a 50% monthly response rate over the study period and were included in the analysis. Elective surgery was paused at 76% of sites in May 2020, 48% of sites in January 2021, and 52% of sites in January 2022. Over those same periods, coinciding with COVID-19 incidence waves, TURBT was restricted at 10%, 14%, and 14% of sites, respectively, radical cystectomy was restricted at 10%, 14%, and 19% of sites, respectively, and cystoscopy was restricted at 33%, 0%, and 10% of sites, respectively. CONCLUSIONS: Bladder cancer care was minimally restricted compared with more pronounced restrictions seen in general elective surgeries during the COVID-19 pandemic.

Local tree cover predicts mosquito species richness and disease vector presence in a tropical countryside landscape.

Context: Land use change drives both biodiversity loss and zoonotic disease transmission in tropical countryside landscapes. Developing solutions for protecting countryside biodiversity, public health, and livelihoods requires understanding the scales at which habitat characteristics such as land cover shape biodiversity, especially for arthropods that transmit pathogens. Evidence increasingly shows that species richness for many taxa correlates with local tree cover. Objectives: We investigated whether mosquito species richness, community composition, and presence of disease vector species responded to land use and tree cover - and if so, whether at spatial scales similar to other taxa. Methods: We paired a field survey of mosquito communities in agricultural, residential, and forested lands in rural southern Costa Rica with remotely sensed tree cover data. We compared mosquito community responses to tree cover surrounding survey sites measured across scales, and analyzed community responses to land use and environmental gradients. Results: Tree cover was positively correlated with mosquito species richness, and negatively correlated with the presence of the common invasive dengue vector Aedes albopictus , particularly at small spatial scales of 80 - 200m. Land use predicted community composition and Ae. albopictus presence. Environmental gradients of tree cover, temperature, and elevation explained 7% of species turnover among survey sites. Conclusions: The results suggest that preservation and expansion of tree cover at local scales can protect biodiversity for a wide range of taxa, including arthropods, and also confer protection against disease vector occurrence. The identified spatial range of tree cover benefits can inform land management for conservation and public health protection.

Anti-PD-1 immunotherapy with androgen deprivation therapy induces robust immune infiltration in metastatic castration-sensitive prostate cancer.

When compared to other malignancies, the tumor microenvironment (TME) of primary and castration-resistant prostate cancer (CRPC) is relatively devoid of immune infiltrates. While androgen deprivation therapy (ADT) induces a complex immune infiltrate in localized prostate cancer, the composition of the TME in metastatic castration-sensitive prostate cancer (mCSPC), and the effects of ADT and other treatments in this context are poorly understood. Here, we perform a comprehensive single-cell RNA sequencing (scRNA-seq) profiling of metastatic sites from patients participating in a phase 2 clinical trial (NCT03951831) that evaluated standard-of-care chemo-hormonal therapy combined with anti-PD-1 immunotherapy. We perform a longitudinal, protein activity-based analysis of TME subpopulations, revealing immune subpopulations conserved across multiple metastatic sites. We also observe dynamic changes in these immune subpopulations in response to treatment and a correlation with clinical outcomes. Our study uncovers a therapy-resistant, transcriptionally distinct tumor subpopulation that expands in cell number in treatment-refractory patients.

The State of Urotrauma Education Among Residency Programs in the United States: A Systematic Review and Meta-Analysis.

PURPOSE OF REVIEW: Management of urotrauma is a crucial part of a urologist's knowledge and training. We therefore sought to understand the state of urotrauma education in the United States. RECENT FINDINGS: Using themes of "Urotrauma" and "Education," we performed a systematic review and meta-analysis by searching for studies in MEDLINE, all Cochrane libraries, EMBASE, BIOSIS, Scopus, and Web of Science through May 2023. The primary outcome was the pooled rate of urology trainee and program director attitudes toward urotrauma education. Secondary outcomes involved a descriptive summary of existing urotrauma curricula and an assessment of factors affecting urotrauma exposure. Of 12,230 unique records, 11 studies met the final eligibility criteria, and we included 2 in the meta-analysis. The majority of trainees and program directors reported having level 1 trauma center rotations (range 88-89%) and considered urotrauma exposure as an important aspect of residency education (83%, 95% CI 76-88%). Despite possible increases in trainee exposure to Society of Genitourinary Reconstructive Surgeons (GURS) faculty over the preceding decade, nearly a third of trainees and program directors currently felt there remained inadequate exposure to urotrauma during training (32%, 95% CI 19-46%). Factors affecting urotrauma education include the limited exposure to GURS-trained faculty and clinical factors such as case infrequency and non-operative trauma management. Urology resident exposure to urotrauma is inadequate in many training programs, underscoring the potential value of developing a standardized curriculum to improve urotrauma education for trainees. Further investigation is needed to characterize this issue and to understand how it impacts trainee practice readiness.

Diverse values of nature for sustainability.

Twenty-five years since foundational publications on valuing ecosystem services for human well-being1,2, addressing the global biodiversity crisis3 still implies confronting barriers to incorporating nature's diverse values into decision-making. These barriers include powerful interests supported by current norms and legal rules such as property rights, which determine whose values and which values of nature are acted on. A better understanding of how and why nature is (under)valued is more urgent than ever4. Notwithstanding agreements to incorporate nature's values into actions, including the Kunming-Montreal Global Biodiversity Framework (GBF)5 and the UN Sustainable Development Goals6, predominant environmental and development policies still prioritize a subset of values, particularly those linked to markets, and ignore other ways people relate to and benefit from nature7. Arguably, a 'values crisis' underpins the intertwined crises of biodiversity loss and climate change8, pandemic emergence9 and socio-environmental injustices10. On the basis of more than 50,000 scientific publications, policy documents and Indigenous and local knowledge sources, the Intergovernmental Platform on Biodiversity and Ecosystem Services (IPBES) assessed knowledge on nature's diverse values and valuation methods to gain insights into their role in policymaking and fuller integration into decisions7,11. Applying this evidence, combinations of values-centred approaches are proposed to improve valuation and address barriers to uptake, ultimately leveraging transformative changes towards more just (that is, fair treatment of people and nature, including inter- and intragenerational equity) and sustainable futures.

Longitudinal Changes in the Operative Experience for Junior Urology Residents.

OBJECTIVE: To evaluate longitudinal trends in surgical case volume among junior urology residents. There is growing perception that urology residents are not prepared for independent practice, which may be linked to decreased exposure to major cases early in residency. METHODS: Retrospective review of deidentified case logs from urology residency graduates from 12 academic medical centers in the United States from 2010 to 2017. The primary outcome was the change in major case volume for first-year urology (URO1) residents (after surgery internship), measured using negative binomial regression. RESULTS: A total of 391,399 total cases were logged by 244 residency graduates. Residents performed a median of 509 major cases, 487 minor cases, and 503 endoscopic cases. From 2010 to 2017, the median number of major cases performed by URO1 residents decreased from 64 to 49 (annual incidence rate ratio 0.90, P < .001). This trend was limited to oncology cases, with no change in reconstructive or pediatric cases. The number of major cases decreased more for URO1 residents than for residents at other levels (P-values for interaction <.05). The median number of endoscopic cases performed by URO1 residents increased from 85 to 194 (annual incidence rate ratio 1.09, P < .001), which was also disproportionate to other levels of residency (P-values for interaction <.05). CONCLUSION: There has been a shift in case distribution among URO1 residents, with progressively less exposure to major cases and an increased focus on endoscopic surgery. Further investigation is needed to determine if this trend has implications on the surgical proficiency of residency graduates.

The Utility of Renal Mass Biopsy in Shared Decision-Making for Renal Mass Treatment.

OBJECTIVE: To evaluate the utility of renal mass biopsy (RMB) in shared decision-making for renal mass treatment. Underutilization of RMB for patients with renal masses is due in part to physicians believing that results have limited clinical utility. MATERIALS AND METHODS: This was a prospective study of all patients referred for RMB from October 2019 to October 2021. Patients and physicians completed pre- and post-RMB questionnaires. Questionnaires assessed both parties' perceived utility of RMB and the impact of biopsy results on treatment preference using Likert scales. RESULTS: We enrolled 22 patients with a mean age of 66years (SD 14.5) and mean renal tumor size 3.1 cm (SD 1.4). Five were lost to follow-up (three pre-RMB, two post-RMB). Pre-RMB, 100% of patients believed that a biopsy would help them choose a treatment and 45% were unsure of their treatment preferences. After RMB, 92% perceived their biopsy results as useful and only 9% were unsure of treatment preference. Overall, 100% of patients were glad they had a biopsy. Results led patients and physicians to change their treatment preference in 57% and 40% of cases, respectively. Patients and physicians disagreed about treatment in 81% of cases prior to biopsy, but in only 25% of cases after biopsy. CONCLUSION: Discordance between patient and physician treatment preference for renal masses is higher in the absence of RMB data. Select patients are willing to undergo RMB and RMB data can increase patient confidence and comfort in a shared decision-making approach for renal mass treatment.

Survival outcomes in patients with muscle invasive bladder cancer undergoing radical vs. partial cystectomy.

PURPOSE: While radical cystectomy (RC) is the standard of care for muscle invasive bladder cancer (MIBC), partial cystectomy (PC) is an effective alternative in select patients. We sought to examine differences in survival for RC and PC in a hospital-based registry. MATERIAL AND METHODS: We identified patients diagnosed with cT2-4 bladder cancer who underwent RC or PC from 2003 to 2015 in the National Cancer Database (NCDB). Using inverse probability treatment weighting (IPTW) to control for known confounders, we compared the primary outcome of overall survival (OS) in patients who underwent RC vs. PC. Kaplan-Meier survival analysis, univariable and multivariable Cox proportional hazards modeling were used. We performed a secondary survival analysis for a subcohort of patients with cT2, cN0, tumor size ≤5 cm, and no concurrent carcinoma in situ (CIS), who may be optimal candidates for PC. RESULTS: A total of 22,534 patients met inclusion criteria, of which 6.9% (1,457) underwent PC. RC had longer median OS than PC (67.8 vs. 54.1 months) and on Cox regression analysis (HR 0.88, 95% CI, 0.80-0.95, P = 0.002). However, in our subcohort, there was no difference in OS between RC and PC (HR 1.02, 95% CI, 0.9-1.2, P = 0.74). PC was associated with increased time from surgery to any systemic therapy or death in the subcohort. CONCLUSIONS: Among patients with clinically organ-confined MIBC, PC appears to afford similar survival outcomes to RC in a large national data set. The safety and tolerability of PC may warrant consideration in highly selected patients.

A Phase 1 Trial of Durvalumab in Combination with Bacillus Calmette-Guerin (BCG) or External Beam Radiation Therapy in Patients with BCG-unresponsive Non-muscle-Invasive Bladder Cancer: The Hoosier Cancer Research Network GU16-243 ADAPT-BLADDER Study.

BACKGROUND: Novel treatments and trial designs remain a high priority for bacillus Calmette-Guerin (BCG)-unresponsive non-muscle-invasive bladder cancer (NMIBC) patients. OBJECTIVE: To evaluate the safety and preliminary efficacy of anti-PD-L1 directed therapy with durvalumab (D), durvalumab plus BCG (D + BCG), and durvalumab plus external beam radiation therapy (D + EBRT). DESIGN, SETTING, AND PARTICIPANTS: A multicenter phase 1 trial was conducted at community and academic sites. INTERVENTION: Patients received 1120 mg of D intravenously every 3 wk for eight cycles. D + BCG patients also received full-dose intravesical BCG weekly for 6 wk with BCG maintenance recommended. D + EBRT patients received concurrent EBRT (6 Gy × 3 in cycle 1 only). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Post-treatment cystoscopy and urine cytology were performed at 3 and 6 -mo, with bladder biopsies required at the 6-mo evaluation. The recommended phase 2 dose (RP2D) for each regimen was the primary endpoint. Secondary endpoints included toxicity profiles and complete response (CR) rates. RESULTS AND LIMITATIONS: Twenty-eight patients were treated in the D (n = 3), D + BCG (n = 13), and D + EBRT (n = 12) cohorts. Full-dose D, full-dose BCG, and 6 Gy fractions × 3 were determined as the RP2Ds. One patient (4%) experienced a grade 3 dose limiting toxicity event of autoimmune hepatitis. The 3-mo CR occurred in 64% of all patients and in 33%, 85%, and 50% within the D, D + BCG, and D + EBRT cohorts, respectively. Twelve-month CRs were achieved in 46% of all patients and in 73% of D + BCG and 33% of D + EBRT patients. CONCLUSIONS: D combined with intravesical BCG or EBRT proved feasible and safe in BCG-unresponsive NMIBC patients. Encouraging preliminary efficacy justifies further study of combination therapy approaches. PATIENT SUMMARY: Durvalumab combination therapy can be safely administered to non-muscle-invasive bladder cancer patients with the goal of increasing durable response rates.

Partial cystectomy: Review of a single center experience from 2004 to 2019.

PURPOSE: Partial cystectomy (PC) is a bladder sparing option to treat bladder cancer in a carefully selected group of patients. We sought to analyze outcomes of partial cystectomy (PC) in a contemporary cohort of patients at a single institution. MATERIAL AND METHODS: Records were reviewed for 43 patients with a primary urothelial carcinoma (UC) who had a partial cystectomy with curative intent at Columbia University Medical Center from 2004 to 2019. Endpoints of interest were noninvasive recurrence (defined as any recurrent nonmuscle invasive disease), advanced recurrence (defined as a muscle invasive recurrence or metastasis), and death. We used unadjusted Cox proportional hazards regressions and log rank tests to estimate the association between clinical characteristics and endpoints of interest. RESULTS: Among 43 patients with bladder cancer treated with partial cystectomy, median patient age was 73 years (interquartile range 67-77.5) and 86% were male. Twenty-three percent of patients received preoperative neoadjuvant chemotherapy (NAC) and 49% of patients were given perioperative intravesical chemotherapy at the time of PC. Pathologic stage was

Heterogeneity in the pharmacological management of radiation-induced hemorrhagic cystitis.

BACKGROUND: Radiation-induced hemorrhagic cystitis is a complication of pelvic radiotherapy, with an incidence of up to 5%. The resultant hematuria may be severe and refractory to conservative measures. Our objective was to describe the pattern of inpatient treatments among a cohort of patients with radiation-induced hemorrhagic cystitis requiring pharmacological management. METHODS: We conducted a retrospective case series to identify all inpatient admissions at a single institution during which patients with radiation cystitis underwent pharmacological intervention for refractory hematuria between 2004 and 2019. Patient demographics, medical history, details of radiation therapy, and relevant admission data were collected. Details of treatment, including the use of pharmacotherapy and surgical treatment, were reviewed and summarized. RESULTS: We identified 21 patients who were treated during 26 admissions. Most were male (91%) with a history of external beam radiation therapy (86%), primarily for prostate cancer (85%), and a median age of 73 (IQR: 67-85). Most patients received continuous bladder irrigation as the first intervention during their admission (65%), for a median duration of 40 hours (IQR: 25-59). Eleven separate pharmacologic agents were used, with variations in initial pharmacotherapy utilization over time. Most patients were treated with a combination of surgical and pharmacological interventions (85%). The median length of stay was 9 days (IQR: 5-17) and the 90-day readmission rate was 35%. CONCLUSIONS: Pharmacologic treatment for refractory radiation-induced hemorrhagic cystitis is inconsistent and lacks evidence to support treatment strategies. Further work is needed to determine the optimal management for this morbid complication.

Intravesical Therapy Compared to Radical Cystectomy Among Patients With Non-Muscle Invasive Bladder Cancer Requiring Additional Treatment After Induction BCG.

BACKGROUND: Many patients with recurrent high-risk non-muscle invasive bladder cancer after intravesical bacillus calmette-guerin (BCG) face a difficult decision between radical cystectomy (RC) or salvage intravesical therapy (IVT). We sought to determine if there is a difference in overall survival RC and IVT after previous treatment with BCG. METHODS: We performed a retrospective cohort study of patients with Ta, T1, and Tis bladder cancer treated with induction BCG in the SEER-Medicare dataset from 2000 to 2015. We used a proportional hazards regression model to compare differences in survival between patients having RC and IVT. We adjusted for confounding using a propensity score and stratified our analysis according to timing of treatment and stage at diagnosis. RESULTS: We identified 3940 patients who received either IVT (79%) or RC (21%) following induction BCG. Among patients treated within 12 months of BCG, there was no significant difference in survival between RC and IVT (HR 0.92, 95% CI 0.81-1.04) and 17% of patients having early IVT ultimately required RC. Among patients treated at least 12 months after BCG, RC was associated with worse survival than IVT (HR 1.19, 95% CI 1.06-1.35) and 10% of patients having late IVT ultimately required RC. CONCLUSION: Among patients with bladder cancer who required additional treatments after induction BCG, we did not observe a difference in overall survival between IVT and RC within 12 months of starting BCG. While RC remains the gold-standard for high risk recurrent NMIBC after BCG, bladder preservation with IVT may be appropriate for well-selected patients.

Biodiversity and infrastructure interact to drive tourism to and within Costa Rica.

SignificanceTourism accounts for roughly 10% of global gross domestic product, with nature-based tourism its fastest-growing sector in the past 10 years. Nature-based tourism can theoretically contribute to local and sustainable development by creating attractive livelihoods that support biodiversity conservation, but whether tourists prefer to visit more biodiverse destinations is poorly understood. We examine this question in Costa Rica and find that more biodiverse places tend indeed to attract more tourists, especially where there is infrastructure that makes these places more accessible. Safeguarding terrestrial biodiversity is critical to preserving the substantial economic benefits that countries derive from tourism. Investments in both biodiversity conservation and infrastructure are needed to allow biodiverse countries to rely on tourism for their sustainable development.

Predicting Sepsis in Patients with Ureteral Stones in the Emergency Department.

Background: In the absence of overt infection signs, clinical criteria for early intervention in patients with ureteral stones are poorly defined. We aimed to develop a model that can identify patients who are at risk for developing sepsis if discharged home from the emergency department (ED). Materials and Methods: We retrospectively reviewed patients between January 2010 and December 2019 who were discharged from the ED after diagnosis of ureteral stones. The primary outcome was sepsis requiring urgent surgical decompression. We used multivariable logistic regression to identify predictors of sepsis. We refined the model using backward stepwise regression with a threshold p-value of 0.05. Results: We identified 1331 patients who were discharged from the ED with ureteral stones. Of these patients, 22 (2%) subsequently developed sepsis requiring urgent decompression. In the initial multivariable model, female gender (odds ratio [OR]: 2.82, p = 0.039) and urine white blood cells (WBCs) (OR: 1.02 per cell count, p < 0.001) were predictive of sepsis. After performing backward stepwise regression, female gender, urine WBCs, and leukocytosis (WBCs >15,000/mm3) met criteria for inclusion in the model. A logistic model including these variables predicted sepsis with an internally cross-validated area under the curve (AUC) of 0.79. Among patients with urine cultures completed in the ED, rates of sepsis were 9% in patients with positive cultures and 1% in patients with negative cultures (p < 0.001). Antibiotic usage was not protective against developing sepsis. Conclusions: Sepsis is a rare complication among patients with ureteral stones selected for conservative management. The presence of elevated urine WBCs and female gender can help identify patients who are at risk of developing sepsis. Patients with risk factors should be managed with an increased index of suspicion for infection and may benefit from early intervention to reduce the risk of sepsis. Sepsis is more common in patients with positive urine cultures.