Preference Elicitation and Treatment Decision-Making Among Men Diagnosed With Prostate Cancer: Randomized Controlled Trial Results of Healium.

BACKGROUND: Elicitation of patients' preferences is an integral part of shared decision-making, the recommended approach for prostate cancer decision-making. Existing decision aids for this population often do not specifically focus on patients' preferences. Healium is a brief interactive web-based decision aid that aims to elicit patients' treatment preferences and is designed for a low health literate population. OBJECTIVE: This study used a randomized controlled trial to evaluate whether Healium, designed to target preference elicitation, is as efficacious as Healing Choices, a comprehensive education and decision tool, in improving outcomes for decision-making and emotional quality of life. METHODS: Patients diagnosed with localized prostate cancer who had not yet made a treatment decision were randomly assigned to the brief Healium intervention or Healing Choices, a decision aid previously developed by our group that serves as a virtual information center on prostate cancer diagnosis and treatment. Assessments were completed at baseline, 6 weeks, and 3 months post baseline, and included decisional outcomes (decisional conflict, satisfaction with decision, and preparation for decision-making), and emotional quality of life (anxiety/tension and depression), along with demographics, comorbidities, and health literacy. RESULTS: A total of 327 individuals consented to participate in the study (171 were randomized to the Healium intervention arm and 156 were randomized to Healing Choices). The majority of the sample was non-Hispanic (272/282, 96%), White (239/314, 76%), married (251/320, 78.4%), and was on average 62.4 (SD 6.9) years old. Within both arms, there was a significant decrease in decisional conflict from baseline to 6 weeks postbaseline (Healium, P≤.001; Healing Choices, P≤.001), and a significant increase in satisfaction with one's decision from 6 weeks to 3 months (Healium, P=.04; Healing Choices, P=.01). Within both arms, anxiety/tension (Healium, P=.23; Healing Choices, P=.27) and depression (Healium, P=.001; Healing Choices, P≤.001) decreased from baseline to 6 weeks, but only in the case of depression was the decrease statistically significant. CONCLUSIONS: Healium, our brief decision aid focusing on treatment preference elicitation, is as successful in reducing decisional conflict as our previously tested comprehensive decision aid, Healing Choices, and has the added benefit of brevity, making it the ideal tool for integration into the physician consultation and electronic medical record. TRIAL REGISTRATION: ClinicalTrials.gov NCT05800483; https://clinicaltrials.gov/study/NCT05800483.

Synthesis of porous high-temperature superconductors via a melamine formaldehyde sacrificial template.

Nanostructured high-temperature superconductors YBa2Cu3O6+δ and Bi2Sr2CaCu2O8+δ were synthesised using a melamine formaldehyde sponge as a sacrificial template, via three solution-based approaches. In the case of YBa2Cu3O6+δ , a modified Pechini method produced a material with a superconducting transition at 92 K and a specific surface area of 4.22 m2 g-1. Further analysis with Hg porosimetry determined that the sponge exhibited a porosity of 82%. In the case of Bi2Sr2CaCu2O8+δ , this method produced a material that exhibited superconductivity at 86 K with a specific surface area of 9.62 m2 g-1. Hg-porosimetry determined that the BSCCO sponge exhibited a porosity of 78%.

Tessier 30 Facial Clefts-A Literature Review of 72 Cases (1996-2020), Suggested Treatment Protocol, Outcome Measures, Minimum Dataset for Future Case Reports, and Registries.

INTRODUCTION: Tessier 30 facial cleft is a rare anomaly presenting in the soft and hard tissues over the central lower face. Owing to the rarity of cases and difficulty of treatment, there is no universally accepted surgical management strategy. The last comprehensive literature review of Tessier 30 clefts was in 1996. This report aims to update the literature to inform decision-making on treating Tessier 30 cases. METHODOLOGY: A literature search was performed. PubMed, SCOPUS, and OVID databases were searched. A total of 72 cases in 51 articles were analyzed, looking at demographics, extent of cleft, parent health, family history, procedures, follow-up, existence of other anomalies, and stages of repair. RESULTS: Surgeons are increasingly choosing to repair Tessier 30 defects in one rather than multiple stages. Of the 72 cases studied, only 31 had documented the completed repair of the cleft. All completed soft tissue only defects were repaired in 1 stage of repair (n = 11). Where both soft tissue and mandible was involved (n = 20), 55% (n = 11) had undergone 1-stage repair to address the Tessier 30 cleft. DISCUSSION: We argue that a single-stage approach is preferable to multistage. Primary mucogingivoperiosteoplasty should be undertaken in children at the time of management of the soft tissue cleft. The timing of this procedure should be in the latter half of the first year of life, as this is when mandibular symphyseal fusion normally occurs. We have suggested a treatment protocol and we hope that future case reports use our minimum data set.

PI3Kδ inhibition prevents IL33, ILC2s and inflammatory eosinophils in persistent airway inflammation.

BACKGROUND: Phosphoinositide-3-kinase-delta (PI3Kδ) inhibition is a promising therapeutic approach for inflammatory conditions due to its role in leucocyte proliferation, migration and activation. However, the effect of PI3Kδ inhibition on group 2 innate lymphoid cells (ILC2s) and inflammatory eosinophils remains unknown. Using a murine model exhibiting persistent airway inflammation we sought to understand the effect of PI3Kδ inhibition, montelukast and anti-IL5 antibody treatment on IL33 expression, group-2-innate lymphoid cells, inflammatory eosinophils, and goblet cell metaplasia. RESULTS: Mice were sensitised to house dust mite and after allowing inflammation to resolve, were re-challenged with house dust mite to re-initiate airway inflammation. ILC2s were found to persist in the airways following house dust mite sensitisation and after re-challenge their numbers increased further along with accumulation of inflammatory eosinophils. In contrast to montelukast or anti-IL5 antibody treatment, PI3Kδ inhibition ablated IL33 expression and prevented group-2-innate lymphoid cell accumulation. Only PI3Kδ inhibition and IL5 neutralization reduced the infiltration of inflammatory eosinophils. Moreover, PI3Kδ inhibition reduced goblet cell metaplasia. CONCLUSIONS: Hence, we show that PI3Kδ inhibition dampens allergic inflammatory responses by ablating key cell types and cytokines involved in T-helper-2-driven inflammatory responses.

Improved photodegradation of anionic dyes using a complex graphitic carbon nitride and iron-based metal-organic framework material.

Introducing heterostructures to graphitic carbon nitrides (g-C3N4) can improve the activity of visible-light-driven catalysts for the efficient treatment of multiple toxic pollutants in water. Here, we report for the first time that a complex material can be constructed from oxygen-doped g-C3N4 and a MIL-53(Fe) metal-organic framework using facile hydrothermal synthesis and recycled polyethylene terephthalate from plastic waste. The novel multi-walled nanotube structure of the O-g-C3N4/MIL-53(Fe) composite, which enables the unique interfacial charge transfer at the heterojunction, showed an obvious enhancement in the separation efficiency of the photochemical electron-hole pairs. This resulted in a narrow bandgap energy (2.30 eV, compared to 2.55 eV in O-g-C3N4), high photocurrent intensity (0.17 mA cm-2, compared to 0.12 mA cm-2 and 0.09 mA cm-2 in MIL-53(Fe) and O-g-C3N4, respectively) and excellent catalytic performance in the photodegradation of anionic azo dyes (95% for RR 195 and 99% for RY 145 degraded after 4 h, and only a minor change in the efficiency observed after four consecutive tests). These results demonstrate the development of new catalysts made from waste feedstocks that show high stability, ease of fabrication and can operate in natural light for environmental remediation.

Assessment of bacterial exposure on phagocytic capability and surface marker expression of sputum macrophages and neutrophils in COPD patients.

Defective phagocytosis has been shown in chronic obstructive pulmonary disease (COPD) bronchoalveolar lavage and blood monocyte-derived macrophages. Phagocytic capabilities of sputum macrophages and neutrophils in COPD are unknown. We investigated phagocytosis in these cells from COPD patients and controls. Phagocytosis of Streptococcus pneumoniae or fluorescently labelled non-typeable Haemophilus influenzae (NTHi) by sputum macrophages and neutrophils was determined by gentamycin protection assay (COPD; n = 5) or flow cytometry in 14 COPD patients, 8 healthy smokers (HS) and 9 healthy never-smokers (HNS). Sputum macrophages and neutrophils were differentiated by adherence for the gentamycin protection assay or receptor expression (CD206 and CD66b, respectively), by flow cytometry. The effects of NTHi on macrophage expression of CD206 and CD14 and neutrophil expression of CD16 were determined by flow cytometry. There was greater uptake of S. pneumoniae [~10-fold more colony-forming units (CFU)/ml] by sputum neutrophils compared to macrophages in COPD patients. Flow cytometry showed greater NTHi uptake by neutrophils compared to macrophages in COPD (67 versus 38%, respectively) and HS (61 versus 31%, respectively). NTHi uptake by macrophages was lower in HS (31%, p = 0.019) and COPD patients (38%, p = 0.069) compared to HNS (57%). NTHi uptake by neutrophils was similar between groups. NTHi exposure reduced CD206 and CD14 expression on macrophages and CD16 expression on neutrophils. Sputum neutrophils showed more phagocytic activity than macrophages. There was some evidence that bacterial phagocytosis was impaired in HS sputum macrophages, but no impairment of neutrophils was observed in HS or COPD patients. These results highlight the relative contributions of neutrophils and macrophages to bacterial clearance in COPD.

Improved cancer coping from a web-based intervention for prostate cancer survivors: A randomized controlled trial.

OBJECTIVES: Prostate cancer (PCa) survivors report poor physical functioning alongside negative psychological outcomes as they cope with treatment side effects and practical concerns after treatment completion. This study evaluated PROGRESS, a web-based intervention designed to improve adaptive coping among PCa survivors. METHODS: Localized PCa patients (N = 431) within one year of treatment completion were randomized to receive educational booklets or PROGRESS + educational booklets. Surveys completed at baseline, 1-, 3-, and 6-months assessed patient characteristics; functional quality of life and coping (primary outcomes); and psychosocial outcomes (e.g., self-efficacy, marital communication; secondary outcomes). Intent-to-treat and as-treated analyses were completed to assess change in outcomes from baseline to 6 months using linear mixed effects regression models. RESULTS: In the intent-to-treat analyses, participants randomized to the intervention group had improved diversion coping (i.e., healthy redirection of worrying thoughts about their cancer), but more difficulties in marital communication (ps < 0.05). However, PROGRESS usage was low among those randomized to the intervention group (38.7%). The as-treated analyses found PROGRESS users reported fewer practical concerns but had worse positive coping compared to PROGRESS non-users (ps < 0.05). CONCLUSIONS: The findings suggest PROGRESS may improve certain aspects of adaptive coping among PCa survivors that use the website, but does not adequately address the remaining coping and psychosocial domains. Additional research is needed to better understand the gaps in intervention delivery contributing to low engagement and poor improvement across all domains of functional quality of life and adaptive coping.

Extracapsular extension on multiparametric magnetic resonance imaging better predicts pT3 disease at radical prostatectomy compared to perineural invasion on biopsy.

INTRODUCTION: Risk assessment for non-organ-confined prostate cancer (PCa) is important in the surgical planning for radical prostatectomy (RP). Perineural invasion (PNI) on prostate biopsy has been associated with adverse pathological outcomes at prostatectomy. Similarly, the identification of suspected extracapsular extension (ECE) on multiparametric magnetic resonance imaging (mpMRI) has been shown to predict non-organ-confined disease. However, no prior study has compared these factors in predicting adverse pathology at prostatectomy. We evaluated mpMRI ECE and prostate biopsy PNI on multivariable analysis to determine their ability to predict pathological stage at time of RP. METHODS: We retrospectively investigated the prostatectomy database at our institution to identify men who underwent prostate biopsy with pre-biopsy mpMRI and subsequent RP from 2013-2017. Multivariable regression analysis was performed to compare the association of mpMRI ECE (mECE) and PNI on prostate biopsy on the likelihood of finding pT3 disease on pathology post-prostatectomy. RESULTS: Of a total 454 RP between 2013 and 2017, 191 patients met our inclusion criteria. Stage pT2 and pT3+ were found in 120 (62.8%) and 71 (37.2%) patients, respectively. Patients with mECE had 4.84 cumulative odds of worse pathological stage on RP (p=0.045) compared to PNI on biopsy, which showed cumulative odds of 2.25 (p=0.048). When controlling only for those patients without PNI, mECE was still found to be a significant predictor of pT3 disease at RP (p=0.030); however, in patients without mECE, PNI was not significant (p=0.062). CONCLUSIONS: While mECE and biopsy PNI were both associated with worse pathological stage on RP, mECE had significantly higher cumulative odds compared to PNI. The significant predictive ability of mECE adds further clinical value to the use of mpMRI in PCa management. While validation in a larger cohort is required, these factors have important clinical implications with regards to early diagnosis of advanced disease and surgical planning.

Incidence of Significant Findings of Microhematuria Workup in Women-What Guidelines Work Best?

OBJECTIVE: To apply the American Urogynecological Society (AUGS)/American College of Obstetricians and Gynecologists (ACOG) recommendations of foregoing workup in patients under 50 years of age with less than 25 red cells per high-powered field, to a cohort of asymptomatic microscopic hematuria (AMH) patients, and assess diagnostic accuracy, sensitivity, specificity, positive, and negative predictive value compared to the American Urologic Association (AUA) guidelines. METHODS: Retrospective review of female patients who underwent AMH evaluation from 2012 to 2015. The number of patients who would have avoided workup following the AUGS/ACOG recommendations was determined. Sensitivity, specificity, positive- and negative-predictive value and accuracy of the AUGS/ACOG recommendations compared to AUA guidelines were determined. RESULTS: Six hundred twenty women underwent AMH workup with 265 women undergoing full workup as per the AUA guidelines. Applying the AUGS/ACOG recommendations to this cohort would not have resulted in missed malignant diagnoses. Two tumors were found, both in patients who had undergone complete workup, and for whom AUGS/ACOG recommends workup. Following the AUGS/ACOG recommendations would have avoided workup in 126/620 of all women and 44/265 women who underwent the full AUA workup. In looking at findings of malignancy, the AUGS/ACOG workup had a sensitivity of 100% and a negative predictive value of 100% as compared to the AUA guidelines. CONCLUSION: AUA guidelines may over screen female low risk AMH patients. Extensive workup in a low risk group of female patients does not result in increased cancer diagnoses. Perhaps a more nuanced approach could result in fewer workups without compromising cancer detection.

Prognostic Molecular Signatures for Metastatic Potential in Clinically Low-Risk Stage I and II Clear Cell Renal Cell Carcinomas.

Introduction: For patients with localized node-negative (Stage I and II) clear cell renal cell carcinomas (ccRCC), current clinicopathological staging has limited predictive capability because of their low risk. Analyzing molecular signatures at the time of nephrectomy can aid in understanding future metastatic potential. Objective: Develop a molecular signature that can stratify patients who have clinically low risk ccRCC, but have high risk genetic changes driving an aggressive metastatic phenotype. Patients, Materials, and Methods: Presented is the differential expression of mRNA and miRNA in 44 Stage I and Stage II patients, 21 who developed metastasis within 5 years of nephrectomy, compared to 23 patients who remained disease free for more than 5 years. Extracted RNA from nephrectomy specimens preserved in FFPE blocks was sequenced using RNAseq. MiRNA expression was performed using the TaqMan OpenArray qPCR protocol. Results: One hundred thirty one genes and 2 miRNA were differentially expressed between the two groups. Canonical correlation (CC) analysis was applied and four CCs (CC32, CC20, CC9, and CC7) have an AUC > 0.65 in our dataset with similar predictive power in the TCGA-KIRC dataset. Gene set enrichment showed CC9 as kidney development/adhesion, CC20 as oxidative phosphorylation pathway, CC32 as RNA binding/spindle and CC7 as immune response. In a multivariate Cox model, the four CCs were able to identify high/low risk groups for metastases in the TCGA-KIRC (p < 0.05) with odds ratios of CC32 = 5.7, CC20 = 4.4, CC9 = 3.6, and CC7 = 2.7. Conclusion: These results identify molecular signatures for more aggressive tumors in clinically low risk ccRCC patients who have a higher potential of metastasis than would be expected.

Development and evaluation of a bladder Cancer specific survivorship care plan by patients and clinical care providers: a multi-methods approach.

BACKGROUND, CONTEXT AND PURPOSE: In spite of the mixed evidence for their impact, survivorship Care Plans (SCPs) are recommended to enhance quality of care for cancer survivors. Data on the feasibility of SCPs in bladder cancer (BC) is sparse. Using a mixed-methods approach, this study describes the iterative development, acceptability and feasibility of BC specific SCP (BC-SCP) in clinical settings. METHODS: In Phase I, we developed the BC-SCP. In Phase II, we conducted four focus groups with 19 patients and 15 providers to examine its acceptability and usability challenges. Data analyses using the Atlas.ti program, informed refinement of the BC-SCP. In Phase III, we conducted feasibility testing of the refined BC-SCP with 18 providers from 12 health-centers. An encounter survey was completed after each assessment to examine the feasibility of the BC-SCP. Chi-square and Fisher Exact tests were used for comparative analyses. RESULTS: During phase I, we observed high patient and provider acceptability of the BC-SCP and substantial engagement in improving its content, design, and structure. In Phase II, providers completed 59 BC-SCPs. Mean time for BC-SCP completion was 12.3 min. Providers reported that BC-SCP content was clear, did not hamper clinic flow and was readily completed with easy-to-access information. Comparative analyses to examine differences in SCP completion time by patient clinico-demographic characteristics and provider type revealed no significant differences. CONCLUSIONS: Our BC-SCP has clinical relevance, and can be used in an active practice setting. However, considerable progress will be necessary to achieve implementation of and sharing the BC-SCP with patients and care providers, particularly within the electronic medical record. In summary, BC-SCPs are essential to improve the follow up care of BC survivors. Clinical resources are required to ensure appropriate implementation of BC-SCPs. TRIAL REGISTRATION: Study HUM00056082.

Use of a Risk Stratification Tool to Guide Evaluation of Patients With Asymptomatic Microscopic Hematuria.

OBJECTIVE: To determine if use of the hematuria risk index can reduce testing and cost, while maintaining equivalent lesion detection in patients with asymptomatic microscopic hematuria. MATERIALS AND METHODS: Retrospective cohort study of 1049 patients at single institution. Hematuria risk index score was calculated based on clinical factors including age, sex, smoking history, and degree of hematuria for each patient along with evaluation studies performed and total number of tumors discovered. Cost benefit analysis was performed based on published Medicare averages. RESULTS: Tumor detection rate in overall, low-risk, and moderate-risk groups were 1.2%, 0%, and 2.96% at a total cost of $408,376. When low-risk group is not screened cost decreases to $166,252 with no lesions missed. The cost to discover one lesion/cancer in the overall group was $34,031.3, the cost to find one high-grade clinically significant lesion/cancer was $136,125.3 for the overall group. When the low-risk group was removed, the cost to find a high-grade clinically significant lesion/cancer decreased to $55,417.3 without missing any significant lesions. Ultrasound may be utilized instead of computed tomography with minimal loss of lesion detection in select moderate risk patients. CONCLUSION: None of the low-risk hematuria risk patients were diagnosed with any lesions, as such these patients may not need an evaluation. Furthermore, by utilizing a risk-stratified approach to the assessment of asymptomatic microscopic hematuria health care costs can be significantly decreased with limited negative consequences in terms of lesion detection.

Massive Neobladder Stones in Postcystectomy Patient Lost to Follow Up.

A 59-year-old man with a history of muscle-invasive bladder cancer status post cystectomy with neobladder creation presented to the Emergency Department with a 4-month history of lower abdominal pain, dysuria, and intermittent hematuria. He was found to have 2 massive bladder stones on CT scan, measuring 12 × 10.5 × 14 cm and 6.5 × 7.5 × 10 cm. Stones were successfully removed via open neocystolithotomy. Stones were composed of a mixture of calcium phosphate (80%) and calcium carbonate (20%).

Crystal structure and Hirshfeld surface analysis of (E)-3-(3-iodo-phen-yl)-1-(4-iodo-phen-yl)prop-2-en-1-one.

The title compound, C15H10I2O, is a halogenated chalcone formed from two iodine substituted rings, one para-substituted and the other meta-substituted, linked through a prop-2-en-1-one spacer. In the mol-ecule, the mean planes of the 3-iodo-phenyl and the 4-iodo-phenyl groups are twisted by 46.51 (15)°. The calculated electrostatic potential surfaces show the presence of σ-holes on both substituted iodines. In the crystal, the mol-ecules are linked through type II halogen bonds, forming a sheet structure parallel to the bc plane. Between the sheets, weak inter-molecular C-H⋯π inter-actions are observed. Hirshfeld surface analysis showed that the most significant contacts in the structure are C⋯H/H⋯C (31.9%), followed by H⋯H (21.4%), I⋯H/H⋯I (18.4%). I⋯I (14.5%) and O⋯H/H⋯O (8.1%).

Involving Patients in the Development and Evaluation of an Educational and Training Experiential Intervention (ETEI) to Improve Muscle Invasive Bladder Cancer Treatment Decision-making and Post-operative Self-care: a Mixed Methods Approach.

This study aims to describe the acceptability and feasibility of an educational and training experiential intervention (ETEI) we developed to enhance muscle invasive bladder cancer (MIBC) patients with treatment decision-making and post-operative self-care. Twenty-five patients were randomized to a control group (N = 8) or ETEI group (N = 17). ETEI group participated in a nurse-led session on MIBC education. The control group received diet and nutrition education. Study questionnaires were completed at baseline and at 1-month post-intervention. Our results showed acceptable recruitment (58%) and retention rates (68%). The ETEI group reported increased knowledge (82% vs. 50%), improved decisional support (64% vs. 50%), improved communication (73% vs. 50%), and increased confidence in treatment decisions (73% vs. 50%) compared to the control group. Patients in the control group reported improved diet (50% v. 27%) as well as maintaining a healthy lifestyle (67% vs. 45%) compared to the ETEI group. Patients in the ETEI group reported a significant decrease in cancer worries and increases in self-efficacy beliefs over time compared to the control group. The ETEI was feasible, acceptable, and showed a potential for inducing desired changes in cancer worries and efficacy beliefs.

Size-dependent melting point depression of nickel nanoparticles.

We investigate the phase-transition behaviour of nickel nanoparticles (3-6 nm) via dynamic TEM. The nanoparticles were synthesized within a reverse microemulsion and then monitored via dynamic TEM simultaneously while undergoing controlled heating. The size-dependent melting point depression experimentally observed is compared with, and is in good agreement with existing thermodynamic and molecular dynamic predictions.

Examining the impact of a multimedia intervention on treatment decision-making among newly diagnosed prostate cancer patients: results from a nationwide RCT.

Men diagnosed with early stage prostate cancer face multiple treatment options, each with distinctive side effects that have significant implications for post-treatment quality of life. Healing Choices for Men with Prostate Cancer is a multimedia educational and decision aid program. This nation-wide randomized controlled trial evaluated the impact of Healing Choices on reducing decisional conflict and distress. Eligible prostate cancer patients who called the National Cancer Institute's Cancer Information Service (CIS) were invited to participate. After a baseline interview, participants were randomized to usual personalized consultation with a CIS specialist (comparison condition) or CIS personalized consultation plus the Healing Choices program (intervention condition). The Decision Conflict Scale and Impact of Event Scale assessed decisional conflict about prostate cancer treatment and cancer-related distress, respectively. Analyses evaluated group differences at 2 months postenrollment. Hypothesized moderation of intervention effects by demographic and clinical characteristics were evaluated. The final sample consisted of N = 349 participants (intervention: n = 181; comparison n = 168). Men were on average 64 years old, primarily White, and well educated. The difference in total decisional conflict was not significant (DCS total score; F[1,311] = .99, p = .32). The difference in cancer-related distress at 2 months between the intervention and the comparison groups was not significant (F[1,337] = .01, p = .93). Evaluation of specific decision processes indicated a significant effect on levels of perceived decisional support (intervention, M = 34.8, SD = 15.7; comparison, M = 38.3, SD = 16.1; F[1,337] = 3.74, p = .05). The intervention effect was greatest for nonwhite minority participants (b = -9.65, SE = 4.67) and those with lower educational attainment (b = 3.87, SE = 2.21). This interactive, comprehensive education and decision aid program may be most effective for a subset of prostate cancer patients in need of educational and decisional support.

The effects of repeated Toll-like receptors 2 and 4 stimulation in COPD alveolar macrophages.

Background: COPD is a progressive inflammatory airway disease characterized by increased numbers of alveolar macrophages in the lungs. Bacterial colonization of the lungs is a common feature in COPD and can promote inflammation through continual and repeated Toll-like receptor (TLR) stimulation. We have studied the response of COPD alveolar macrophages to repetitive stimulation with TLR2 and TLR4 ligands. We investigated the effect of sequential stimulation with different ligands to determine whether this results in tolerance or amplification of the immune response. Methods: We stimulated alveolar macrophages from COPD patients (n=9) and smokers (n=8) with the TLR4 agonist lipopolysaccharide (LPS) or the TLR2 agonist Pam3CSK4 for 24 hours before restimulating again for 24 hours. Cytokine protein release and gene expression were investigated. Results: Repetitive stimulation of COPD and smokers macrophages with LPS for both 24-hour periods caused a reduction in tumor necrosis factor α, CCL5, and IL-10 production compared to cells that were not exposed initially to LPS. IL-6 and CXCL8 production were not significantly altered following repetitive LPS stimulation. The same pattern was observed for repeated stimulation with Pam3CSK4. Using COPD macrophages, LPS followed by Pam3CSK4 stimulation increased the levels of all cytokines compared to media followed by Pam3CSK4. Conclusion: TLR tolerance in COPD alveolar macrophages occurs after repetitive stimulation with the same TLR ligand, but this only occurs for selected cytokines. CXCL8 production is not reduced after repetitive TLR stimulation with the same ligand; this may be an important mechanism for the increased CXCL8 levels that have been observed in COPD. We showed that TLR4 stimulation followed by TLR2 stimulation does not cause tolerance, but enhances cytokine production. This may be a relevant mechanism by which bacteria cause excessive inflammation in COPD patients.

Computerized cognitive training in prostate cancer patients on androgen deprivation therapy: a pilot study.

PURPOSE: Prostate cancer patients who have undergone androgen deprivation therapy (ADT) may experience cognitive impairment, yet there is an unmet need for nonpharmacological interventions to address cognitive impairment in this population. This study examines the feasibility, acceptability, and preliminary efficacy of a home-based computerized cognitive training (CCT) program to treat cancer-related cognitive impairment. METHODS: Sixty men who had received ≥ 3 months of ADT were screened for at least mild cognitive or neurobehavioral impairment and randomized to 8 weeks of CCT or usual care. Follow-up assessments occurred immediately post-intervention or equivalent (T2) and 8 weeks later (T3). The acceptability of CCT was also assessed. RESULTS: Feasibility:A priori feasibility thresholds were partially met (i.e., randomization rate > 50%, retention rate > 70% excluding CCT drop-outs, but < 70% for intent-to-treat). Acceptability: Participants were mostly satisfied with CCT and found it somewhat enjoyable, though barriers to uptake existed. Preliminary efficacy: Linear mixed models indicated significant time by group effects favorable to CCT in reaction time (p = .01), but unfavorable to CCT in verbal and visual memory (ps < .05). Memory was temporarily suppressed in the CCT group at T2, but normalized by T3. There was no effect of CCT on self-reported cognitive functioning, neurobehavioral functioning, nor quality of life. CONCLUSIONS: This study provides tentative support for the feasibility and acceptability of CCT to treat mild cognitive impairment in ADT patients. CCT had a beneficial effect on reaction time, but temporarily suppressed memory. CCT's benefits may be limited to a narrow area of functioning. Larger-scale studies are needed.

Racial Disparities in Clinically Significant Prostate Cancer Treatment: The Potential Health Information Technology Offers.

PURPOSE: Black men are more likely to die as a result of prostate cancer than white men, despite effective treatments that improve survival for clinically significant prostate cancer. We undertook this study to identify gaps in prostate cancer care quality, racial disparities in care, and underlying reasons for poorer quality care. METHODS: We identified all black men and random age-matched white men with Gleason scores ≥ 7 diagnosed between 2006 and 2013 at two urban hospitals to determine rates of treatment underuse. Underuse was defined as not receiving primary surgery, cryotherapy, or radiotherapy. We then interviewed treating physicians about the reasons for underuse. RESULTS: Of 359 black and 282 white men, only 25 (4%) experienced treatment underuse, and 23 (92%) of these were black. Most (78%) cases of underuse were due to system failures, where treatment was recommended but not received; 38% of these men continued receiving care at the hospitals. All men with treatment underuse due to system failures were black. CONCLUSION: Treatment rates of prostate cancer are high. Yet, racial disparities in rates and causes of underuse remain. Only black men experienced system failures, a type of underuse amenable to health information technology-based solutions. Institutions are missing opportunities to use their health information technology capabilities to reduce disparities in cancer care.