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BackgroundFinancial toxicity is emerging as an important patient-centered outcome and is understudied in prostate cancer patients. We sought to understand the association between financial burden and treatment regret in men with localized prostate cancer to better evaluate the role of financial discussions in patient counseling.MethodsUtilizing the Comparative Effectiveness Analysis of Surgery and Radiation dataset, we identified all men accrued between 2011 and 2012 who underwent surgery, radiation, or active surveillance for localized prostate cancer. Financial burden and treatment regret were assessed at 3- and 5-year follow-up. The association between financial burden and regret was assessed using multivariable longitudinal logistic regression controlling for demographic and disease characteristics, treatment, functional outcomes, and patient expectations.ResultsOf the 2924 eligible patients, regret and financial burden assessments for 3- and/or 5-year follow-up were available for 81% (n = 2359). After adjustment for relevant covariates, financial burden from "finances in general" was associated with treatment regret at 3 years (odds ratio [OR] = 2.47, 95% confidence interval [CI] = 1.33 to 4.57; P = .004); however, this association was no longer statistically significant at 5-year follow-up (OR = 1.19, 95% CI = 0.56 to 2.54; P = .7).ConclusionsIn this population-based sample of men with localized prostate cancer, we observed associations between financial burden and treatment regret. Our findings suggest indirect treatment costs, especially during the first 3 years after diagnosis, may impact patients more profoundly than direct costs and are important for inclusion in shared decision making. more...

Light is a potent circadian entraining agent. For many people, daily light exposure is fundamentally dysregulated with reduced light during the day and increased light into the late evening. This lighting schedule promotes chronic disruption to circadian physiology resulting in a myriad of impairments. Developmental changes in sleep-wake physiology suggest that such light exposure patterns may be particularly disruptive for adolescents and further compounded by lifestyle factors such as early school start times. This narrative review describes evidence that reduced light exposure during the school day delays the circadian clock, and longer exposure durations to light-emitting electronic devices in the evening suppress melatonin. While home lighting in the evening can suppress melatonin secretion and delay circadian phase, the patterning of light exposure across the day and evening can have moderating effects. Photic countermeasures may be flexibly and scalably implemented to support sleep-wake health; including manipulations of light intensity, spectra, duration and delivery modality across multiple contexts. An integrative approach addressing physiology, attitudes, and behaviors will support optimization of light-driven sleep-wake outcomes in adolescents. more...

Introduction and objectiveThe timing of radiotherapy (RT) after prostatectomy is controversial, and its effect on sexual, urinary, and bowel function is unknown. This study seeks to compare patient-reported functional outcomes after radical prostatectomy (RP) and postprostatectomy radiation as well as elucidate the timing of radiation to allow optimal recovery of function.MethodsThe Comparative Effectiveness Analysis of Surgery and Radiation (CEASAR) study is a prospective, population-based, observational study of men with localized prostate cancer. Patient-reported sexual, urinary, and bowel functional outcomes were measured using the 26-item Expanded Prostate Index Composite at baseline and at 6, 12, 36, and 60 months after enrollment. Functional outcomes were compared among men undergoing RP alone, post-RP adjuvant radiation (RP + aRT), and post-RP salvage radiation (RP + sRT) using multivariable models controlling for baseline clinical, demographic, and functional characteristics.ResultsAmong 1,482 CEASAR participants initially treated with RP for clinically localized prostate cancer, 11.5% (N = 170) received adjuvant (aRT, N = 57) or salvage (sRT, N = 113) radiation. Men who received post-RP RT had worse scores in all domains (sexual function [-9.0, 95% confidence interval {-14.5, -3.6}, P < 0.001], incontinence [-8.8, {-14.0, -3.6}, P < 0.001], irritative voiding [-5.9, {-9.0, -2.8}, P < 0.001], bowel irritative [-3.5, {-5.8, -1.2}, P = 0.002], and hormonal function [-4.5, {-7.2, -1.7}, P = 0.001]) compared to RP alone at 5 years of follow-up. Compared to men treated with RP alone in an adjusted linear model, sRT was associated with significantly worse scores in all functional domains. aRT was associated with significantly worse incontinence, urinary irritation, and hormonal function domain scores compared to RP alone at 5 years of follow-up. On multivariable modeling, RT administered approximately 24 months after RP was associated with the smallest decline in sexual domain score, with an adjusted mean decrease of 8.85 points (95% confidence interval [-19.8, 2.1]) from post-RP, pre-RT baseline.ConclusionsIn men with localized prostate cancer, post-RP RT was associated with significantly worse sexual, urinary, and bowel function domain scores at 5 years compared to RP alone. Radiation delayed for approximately 24 months after RP may be optimal for preserving erectile function compared to radiation administered closer to the time of RP. more...

In vivo bioluminescence imaging has been used to monitor Staphylococcus aureus infections in preclinical models by employing bacterial reporter strains possessing a modified lux operon from Photorhabdus luminescens. However, the relatively short emission wavelength of lux (peak 490 nm) has limited tissue penetration. To overcome this limitation, the gene for the click beetle (Pyrophorus plagiophtalamus) red luciferase (luc) (with a longer >600 emission wavelength), was introduced singly and in combination with the lux operon into a methicillin-resistant S. aureus strain. After administration of the substrate D-luciferin, the luc bioluminescent signal was substantially greater than the lux signal in vitro. The luc signal had enhanced tissue penetration and improved anatomical co-registration with infected internal organs compared with the lux signal in a mouse model of S. aureus bacteremia with a sensitivity of approximately 3 × 104 CFU from the kidneys. Finally, in an in vivo mixed bacterial wound infection mouse model, S. aureus luc signals could be spectrally unmixed from Pseudomonas aeruginosa lux signals to noninvasively monitor the bacterial burden of both strains. Therefore, the S. aureus luc reporter may provide a technological advance for monitoring invasive organ dissemination during S. aureus bacteremia and for studying bacterial dynamics during mixed infections. more...

Purpose: AUA guidelines prioritize nephron sparing in patients with preexisting chronic kidney disease (CKD). However, few studies analyze long-term renal function in patients with preoperative severe CKD who undergo extirpative renal surgery. Herein, we compare the hazard of progression to end-stage kidney disease (ESKD) following partial nephrectomy (PN) and radical nephrectomy (RN) among patients with preoperative severe CKD. Materials and Methods: Patients with stage 4 CKD who underwent PN or RN from 1970 to 2018 were identified. A multivariable Fine-Gray subdistribution hazard model was employed to assess associations with progression to ESKD accounting for the competing risk of death. Results: A total of 186 patients with stage 4 CKD underwent PN (n = 71; 38%) or RN (n = 115; 62%) for renal neoplasms with median follow-up of 6.9 years (interquartile range 3.8-14.1). On multivariable analyses adjusting for competing risk of death, the subdistribution hazard ratio (SHR) for older age at surgery (SHR for 5-year increase 0.81; 95% CI 0.73-0.91; P <.001) and higher preoperative estimated glomerular filtration rate (SHR for 5-unit increase 0.63; 95% CI 0.47-0.84; P =.002) was associated with lower hazard of progression to ESKD. There was no significant difference in hazard of ESKD between PN and RN (SHR 0.82; 95% CI 0.50-1.33; P =.4). Conclusions: Among patients with preoperative severe CKD, higher preoperative estimated glomerular filtration rate was associated with lower hazard of progression to ESKD after extirpative surgery for renal neoplasms. We did not observe a significant difference in overall hazard for developing ESKD between PN and RN. [ABSTRACT FROM AUTHOR] more...

Objective: To quantify the rate of progression in surveilled cysts and assess what factors should indicate delayed resection. Background: Side-branch intraductal papillary mucinous neoplasms (SB-IPMNs) are increasingly discovered, making it challenging to identify which patients require resection, thus avoiding inappropriate treatment. Most incidental lesions are surveyed, yet the consequences of that decision remain uncertain. Methods: A prospectively maintained database of pancreatic cystic neoplasms was queried for patients with SB-IPMN. Patients with ≥ 2 imaging studies >6 months apart were included. Clinically relevant progression (CR-progression) was defined by symptoms, worrisome/high-risk stigmata, or invasive cancer (IC). Growth ≥ 5 mm in 2 years is considered CR-progression; size ≥3 cm alone is not. Results: Between 1997 and 2023, 1337 patients were diagnosed with SB-IPMN. Thirty-seven (2.7%) underwent up-front surgery; 1000 (75.0%) had >6 months of surveillance. The rate of CR-progression was 15.3% (n = 153) based on size increase (n = 63, 6.3%), mainduct involvement (n = 48, 4.8%), symptoms (n = 8, 5.0%), or other criteria (n = 34, 3.4%). At a median follow-up of 6.6 years (interquartile range: 3.0-10.26), 17 patients (1.7%) developed IC. Those with CR-progression developed IC in 11.1% (n = 17) and highgrade dysplasia (HGD) in 6.5% (n = 10). Nearly half of the cancers were not contiguous with the surveyed SB-IPMN. Size ≥3 cm was not associated with HGD/IC (P = 0.232). HGD/IC was least common in CR-progression determined by size growth (6.3%) versus main-duct involvement (24%) or other (43%, P < 0.001) Patients with CR-progression demonstrated improved survival (overall survival) with resection on time-to-event (P < 0.001) and multivariate Cox regression (hazard ratio = 0.205, 0.096-0.439, P < 0.001) analyses. Overall survival was not improved with resection in all patients (P = 0.244). Conclusions: CR-progression for SB-IPMNs is uncommon, with the development of cancer anywhere in the pancreas being rare. Initial size should not drive resection. Long-term and consistent nonoperative surveillance is warranted, with surgery currently reserved for CR-progression, knowing that the majority of these still harbor low-grade pathology. [ABSTRACT FROM AUTHOR] more...

Purpose: Multiple prognostic models exist to assess survival among patients with metastatic clear cell renal cell carcinoma. However, the relative contribution of histopathological features of the metastasis has not been extensively studied. Herein, we compared models using clinical, primary tumor, and metastatic features to predict cancer-specific survival for patients with surgically resected metastatic clear cell renal cell carcinoma. Materials and Methods: We studied 266 patients who had undergone nephrectomy between 1970 and 2019, and who had a single site of metastasis completely resected. Two versions of the metastatic clear cell renal cell carcinoma score published by Leibovich et al were calculated, using grade and necrosis from the primary tumor and using grade and necrosis from the metastasis. Predictive abilities of these 2 versions and a third model that included metastatic features only were compared using c-indexes from Cox proportional hazards models. Results: A total of 197 patients died from renal cell carcinoma at a median of 2.3 years (IQR 1.1-4.5); median follow-up among survivors was 13.2 years (IQR 10.0-14.5). The Leibovich score using grade and necrosis from the metastasis (c[0.679) had similar predictive ability compared to the original Leibovich score using grade and necrosis from the primary tumor (c[0.675). A third model (c[0.707) demonstrated that metastasectomy within 2 years after nephrectomy, presence of bone metastasis, high grade, and sarcomatoid differentiation in the metastasis were significantly associated with cancer-specific survival. Conclusions: Scoring algorithms calculated using histopathological features of the metastasis can be used to predict cancer-specific survival for patients with surgically resected metastatic clear cell renal cell carcinoma. These findings are of particular importance for instances when primary tumor histopathology is not readily available. [ABSTRACT FROM AUTHOR] more...

Purpose: Assessments of financial toxicity among patients with metastatic prostate cancer are lacking. Using patient surveys, we sought to identify coping mechanisms and assess characteristics associated with lower financial toxicity. Materials and Methods: Surveys were administered to all patients seen at a single center’s Advanced Prostate Cancer Clinic over a 3-month period. Surveys included the COST-FACIT (COmprehensive Score for Financial Toxicity) and coping mechanism questionnaires. Patients with metastatic disease (lymph nodes, bone, visceral) were included for analysis. Coping mechanisms were compared between patients experiencing low (COST-FACIT >24) vs high (COST-FACIT≤ 24) financial toxicity using Fisher’s exact test. Multivariable linear regression was used to evaluate characteristics associated with lower financial toxicity. Results: Overall, 281 patients met inclusion criteria of which 79 reported high financial toxicity. In multivariable analysis, characteristics associated with lower financial toxicity included older age (estimate: 0.36, 95%CI: 0.21-0.52), applying for patient assistance programs (estimate: 4.42, 95%CI: 1.72-7.11), and an annual income of at least $100,000 (estimate: 7.81, 95%CI: 0.97, 14.66). Patients with high financial toxicity were more likely to decrease spending on basic goods (35% vs 2.5%, P < .001) and leisure activities (59% vs 15%, P > .001), as well as use savings (62% vs 17%, P < .001) to pay for their treatment. Conclusions: In this cross-sectional study, patients with metastatic prostate cancer and high financial toxicity were more likely to decrease spending on basic goods and leisure activities and use savings to pay for care. Understanding the impact of financial toxicity on patients’ lives is crucial to inform shared decisionmaking and interventions designed to mitigate financial toxicity in this population. [ABSTRACT FROM AUTHOR] more...

Patients commonly use the internet to obtain medical information. Patients in our outpatient setting frequently have incomplete or even incorrect information about hyperthermic intraperitoneal chemotherapy that they have found on the internet. We aimed to assess the quality and content of Web-based information on hyperthermic intraperitoneal chemotherapy using validated and novel scoring systems. The keywords "HIPEC" and "hyperthermic intraperitoneal chemotherapy" were entered into the most commonly used internet search engines (Google, Bing, and Yahoo). The first 10 websites from each search were analyzed. Website quality was assessed using the validated Journal of the American Medical Association benchmark criteria and DISCERN scoring systems. We created a novel hyperthermic intraperitoneal chemotherapy–specific score with surgeon experts in the field. Eighteen unique websites were identified. The majority (78%) were from academic institutions. The mean total DISCERN score for all websites was 41.8 ± 8.4 (maximum possible points = 75). The mean Journal of the American Medical Association and hyperthermic intraperitoneal chemotherapy–specific scores were 1.72 ± 1.13 (maximum possible score = 4) and 11.5 ± 4.5 (maximum possible score = 31), respectively. The lowest Journal of the American Medical Association scores were in the category of authorship. In total, 78% of websites omitted author details; 83% and 78% included the temperature and duration of hyperthermic intraperitoneal chemotherapy, respectively. Only 39% of websites mentioned complications of hyperthermic intraperitoneal chemotherapy. Web-based information on hyperthermic intraperitoneal chemotherapy is of variable content and quality. None of the websites achieved maximum scores using any of the scoring tools. Less than half of the websites provided any information on possible complications of the procedure. These findings should be highlighted to patients using the internet to obtain information about hyperthermic intraperitoneal chemotherapy. [ABSTRACT FROM AUTHOR] more...

Phosphodiesterase 4 (PDE4) is highly expressed in keratinocytes and immune cells and promotes pro‐inflammatory responses upon activation. The activity of PDE4 has been attributed to various inflammatory conditions, leading to the development and approval of PDE4 inhibitors as host‐directed therapeutics in humans. For example, the topical PDE4 inhibitor, crisaborole, is approved for the treatment of mild‐to‐moderate atopic dermatitis and has shown efficacy in patients with psoriasis. However, the role of crisaborole in regulating the immunopathogenesis of inflammatory skin diseases and infection is not entirely known. Therefore, we evaluated the effects of crisaborole in multiple mouse models, including psoriasis‐like dermatitis, AD‐like skin inflammation with and without filaggrin mutations, and Staphylococcus aureus skin infection. We discovered that crisaborole dampens myeloid cells and itch in the skin during psoriasis‐like dermatitis. Furthermore, crisaborole was effective in reducing skin inflammation in the context of filaggrin deficiency. Importantly, crisaborole reduced S. aureus skin colonization during AD‐like skin inflammation. However, crisaborole was not efficacious in treating S. aureus skin infections, even as adjunctive therapy to antibiotics. Taken together, we found that crisaborole reduced itch during psoriasis‐like dermatitis and decreased S. aureus skin colonization upon AD‐like skin inflammation, which act as additional mechanisms by which crisaborole dampens the immunopathogenesis in mouse models of inflammatory skin diseases. Further examination is warranted to translate these preclinical findings to human disease. [ABSTRACT FROM AUTHOR] more...

Purpose: The KEYNOTE-564 trial demonstrated that adjuvant pembrolizumab after nephrectomy for clear cell renal cell carcinoma decreased the risk of disease progression and potentially overall mortality as well. Herein, we used a Markov model to weigh the costs, toxicities, and efficacy of pembrolizumab to further investigate its utility. Materials and Methods: Decision-analytic Markov modeling was used to conduct a cost-utility analysis of adjuvant pembrolizumab versus observation after nephrectomy for high-risk clear cell renal cell carcinoma, using data from KEYNOTE-564 to inform model probabilities. Primary outcomes were quality-adjusted life years, Medicare costs, and incremental cost-effectiveness ratios. The willingness-to-pay threshold utilized was $100,000/quality-adjusted life year. Results: At 5 years, adjuvant treatment with pembrolizumab resulted in 0.3 additional quality-adjusted life years at an additional cost of $99,484 relative to observation. Pembrolizumab was found not to be cost-effective at a 5-year time horizon (incremental cost-effectiveness ratio[$326,534). On sensitivity analysis, pembrolizumab became cost-effective if its per cycle cost was <$5,064 (base =$10,278) or its 5-year progression benefit was >18.8% (base 9%). Upon simulation, pembrolizumab was cost-effective for 29% of patients at 5 years. Specifically, we found that pembrolizumab would be cost-effective at 5 years for patients with at least a 59% 5 year risk of progression, which corresponds to a Mayo Progression-free Survival Score ≤10. Conclusions: At current prices, adjuvant pembrolizumab was found to be costeffective only for the highest risk subset of clear cell renal cell carcinoma patients 5 years after treatment, including patients with complete metastasectomy, regional lymph node involvement, or ≤ 7cm pT3 tumors with sarcomatoid features. Longer-term trial data, including overall survival results, are necessary to confirm these extrapolations. [ABSTRACT FROM AUTHOR] more...

Purpose: Out-of-pocket costs represent an important component of financial toxicity and may impact patients’ receipt of care. Herein, we evaluated patientlevel factors associated with out-of-pocket costs for contemporary advanced prostate cancer treatment options. Materials and Methods: We identified all commercially insured men receiving treatment for advanced prostate cancer between 2007 and 2019 within the OptumLabs Data Warehouse(. Patients were categorized into 3 treatment groups: androgen deprivation monotherapy, novel hormonal therapy, and nonandrogen systemic therapy. The primary outcome was out-of-pocket costs in the first year of treatment. The associations of treatment and patient variables with out-of-pocket costs were assessed using multivariable regression models. All costs were adjusted to reflect 2019 U.S. dollars using the Consumer Price Index. Results: In a cohort of 13,409 men 81% (n [ 10,926) received androgen deprivation monotherapy, 6% (n [ 832) novel hormonal therapy, and 12% (n [ 1,651) nonandrogen systemic therapy. Mean treatment-related out-of-pocket costs in the first year were $165, $4,236, and $994 for androgen deprivation monotherapy, novel hormonal therapy, and nonandrogen systemic therapy, respectively. The adjusted difference in annual treatment-related out-of-pocket costs for novel hormonal therapy and nonandrogen systemic therapy were $2,581 (95% CI: $1,923-$3,240) and $752 (95% CI: $600-$903) higher than androgen deprivation monotherapy, respectively. Patient characteristics associated (P < .05) with higher treatment-related outof-pocket costs included older age (65-74 years), Black race, lower comorbidity scores, and lower household income. Conclusions: Patients receiving novel hormonal therapy for advanced prostate cancer had substantially higher treatment-related out-of-pocket costs. In addition to raising awareness among prescribers, these data support the inclusion of treatment associated financial toxicity in shared decision making for advanced prostate cancer and call attention to subgroups of patients particularly vulnerable to financial toxicity. [ABSTRACT FROM AUTHOR] more...

Purpose: Conversions from partial to radical nephrectomy are uncommon and reports on this topic are rare. In this study we present a detailed analysis of conversions from partial to radical nephrectomy in a single-institutional contemporary experience and provide an analysis of preoperative risk factors. Materials and Methods: Patients who underwent converted (cases) and completed (controls) partial nephrectomy from 2000 to 2015 were matched 1:1 for analysis. Perioperative imaging was reviewed and RENAL (for radius, exophytic/ endophytic properties, anterior/posterior descriptor, and location relative to the polar line) nephrometry scores were calculated. Reasons for conversions were abstracted from operative reports. Multivariable conditional logistic regression analyses were used to assess preoperative risk factors for conversion. Results: A total of 168 cases (6.1% of all partial nephrectomies) were identified and matched on tumor size, year of surgery, and surgical approach to 168 controls. Conversion rates decreased from 13% in 2000-2003 to 4% in 2012-2015. Oncologic considerations, such as concern for upstaging and positive margins, were the most cited (56%) reasons for conversion. On multivariable analyses, male sex (odds ratio 2.34; P [ .03), Charlson score (odds ratio per 1-unit increase: 1.28; P [ .03), posterior and middle (on anteroposterior axis) location (reference: anterior, odds ratio 2.83, P [ .02 and odds ratio 6.38, P < .001, respectively) and hilar location (reference: peripheral/central, odds ratio 5.61; P < .001) were associated with increased odds of conversion. Conclusions: Rates of conversion from partial to radical nephrectomy in our experience were low and decreased over time. Preoperative characteristics such as hilar, posterior, and middle locations were significantly associated with conversions after controlling for tumor size, and offer guidance for operative planning and patient counseling. [ABSTRACT FROM AUTHOR] more...

This study aimed to assess the correlation between validated measures of physical status in a prehabilitation regimen with an established frailty score and analyze changes in these measures after completion of a directed prehabilitation program among patients undergoing elective pancreatic resection. Adult patients undergoing pancreatic resection from 2019−2021 were enrolled in a pilot prehabilitation program. Three validated measures of physical status were used: the 6-minute walk test, grip strength, and chair-stand test. The prehabilitation program comprised 7,500 steps, 30 grip strength exercises, and 100 chair-stand exercises daily. Patients' frailty score was calculated using the Modified Johns Hopkins Frailty score. Changes in physical status measures after prehabilitation and postoperative outcomes were compared. Thirty-two patients with a median age of 69.0 years (interquartile range = 59.5−76.3 years) were included. Patients' median duration of participation was 21.5 days (interquartile range = 16−29 days). There was a negative correlation between increasing frailty score and baseline the 6-minute walk test (R2 = 0.17) and chair-stand test (R2 = 0.18). Patients' mean the 6-minute walk test decreased at the end of the prehabilitation program, while grip strength and chair-stand test were unchanged. When stratified by low or intermediate and high frailty scores, the differences in the 6-minute walk test and chair-stand test were unchanged. Hospital duration of stay, complications, and 90-day readmission rates were not different between frailty groups (P >.05). Correlation of physical status measures with frailty score suggests only one of these measures is sufficient to estimate patients' preoperative physical status. A longer, more comprehensive prehabilitation program or an expedited operation are likely the best strategies to improve patient outcomes. [ABSTRACT FROM AUTHOR] more...

C‐C motif chemokine receptor 2 (CCR2) is an important mediator of myeloid cell chemotaxis during inflammation and infection. Myeloid cells such as monocytes, macrophages, and neutrophils contribute to host defense during orthopedic implant‐associated infections (OIAI), but whether CCR2‐mediated chemotaxis is involved remains unclear. Therefore, a Staphylococcus aureus OIAI model was performed by surgically placing an orthopedic‐grade titanium implant and inoculating a bioluminescent S. aureus strain in knee joints of wildtype (wt) and CCR2‐deficient mice. In vivo bioluminescent signals significantly increased in CCR2‐deficient mice compared with wt mice at later time points (Days 14–28), which was confirmed with ex vivo colony‐forming unit enumeration. S. aureus γ‐hemolysin utilizes CCR2 to induce host cell lysis. However, there were no differences in bacterial burden when the OIAI model was performed with a parental versus a mutant γ‐hemolysin‐deficient S. aureus strain, indicating that the protection was mediated by the host cell function of CCR2 rather than γ‐hemolysin virulence. Although CCR2‐deficient and wt mice had similar cellular infiltrates in the infected joint tissue, CCR2‐deficient mice had reduced myeloid cells and γδ T cells in the draining lymph nodes. Taken together, CCR2 contributed to host defense at later time points during an OIAI by increasing immune cell infiltrates in the draining lymph nodes, which likely contained the infection and prevented invasive spread. [ABSTRACT FROM AUTHOR] more...