Purpose
To define the role of focal laser ablation (FLA) as clinical treatment of prostate cancer (PCa) using the Delphi consensus method.
Methods
A panel of international experts in the field of ...focal therapy (FT) in PCa conducted a collaborative consensus project using the Delphi method. Experts were invited to online questionnaires focusing on patient selection and treatment of PCa with FLA during four subsequent rounds. After each round, outcomes were displayed, and questionnaires were modified based on the comments provided by panelists. Results were finalized and discussed during face-to-face meetings.
Results
Thirty-seven experts agreed to participate, and consensus was achieved on 39/43 topics. Clinically significant PCa (csPCa) was defined as any volume Grade Group 2 Gleason score (GS) 3+4. Focal therapy was specified as treatment of all csPCa and can be considered primary treatment as an alternative to radical treatment in carefully selected patients. In patients with intermediate-risk PCa (GS 3+4) as well as patients with MRI-visible and biopsy-confirmed local recurrence, FLA is optimal for targeted ablation of a specific magnetic resonance imaging (MRI)-visible focus. However, FLA should not be applied to candidates for active surveillance and close follow-up is required. Suitability for FLA is based on tumor volume, location to vital structures, GS, MRI-visibility, and biopsy confirmation.
Conclusion
Focal laser ablation is a promising technique for treatment of clinically localized PCa and should ideally be performed within approved clinical trials. So far, only few studies have reported on FLA and further validation with longer follow-up is mandatory before widespread clinical implementation is justified.
Venous leg ulcers, which may take months to heal, account for 40–70% of all lower extremity chronic wounds. New treatment options for venous leg ulcers have recently been proposed, and therefore ...deciding which patients are candidates for these novel—and often expensive—treatments is an important task. Moreover, researchers conducting clinical trials often wish to enrol patients who are unlikely to heal in order to minimize sample sizes needed and research costs. Our purpose was to assess the use of percentage change in venous leg ulcer area over the first few weeks of treatment as a prognostic indicator of healing or non‐healing at 24 weeks. We conducted a cohort study based on an existing data set from a multicentre randomized clinical trial that enrolled 104 patients. Wounds were measured using digital planimetry for 4 consecutive weeks following the inception of good wound care. Utilizing the Wilcoxon rank sum (Mann–Whitney) test, we found that percentage change in area over time distinguished between those who healed and those who failed to heal after 24 weeks of good wound care (P < 0·05). The rate of healing, or area healed per week, did not differentiate between those who healed at 24 weeks and those who did not, as all patients had similar rates of healing over the first 4 weeks of treatment. Percentage change in area from baseline to week 4 provided the best combination of positive and negative predictive values (68·2%, 74·7%) and the largest area under the receiver operating characteristic curve (0·75). Thus, percentage change in area over the first 4 weeks of treatment represents a practical and predictive measure of complete wound healing by 24 weeks.
In four laboratory studies, we find that regulatory focus induced by situational cues (such as the framing of an unrelated task) or primed influences people’s likelihood to cross ethical boundaries. ...A promotion focus leads individuals to be more likely to act unethically than a prevention focus (Studies 1, 2, and 3). These higher levels of dishonesty are explained by the influence of a person’s induced regulatory focus on his or her behavior toward risk. A promotion focus leads to risk-seeking behaviors, while a prevention focus leads to risk avoidance (Study 3). Through higher levels of dishonesty, promotion focus also results in higher levels of virtuous behavior (Studies 2 and 3), thus providing evidence for compensatory ethics. Our results also demonstrate that the framing of ethics (e.g., through an organization’s ethics code) influences individuals’ ethical behavior and does so differently depending on an individual’s induced regulatory focus (Study 4).
Magnetic resonance imaging (MRI) is emerging as a robust, noninvasive method for detecting and characterizing prostate cancer (PCa), but limitations remain in its ability to distinguish cancerous ...from non-cancerous tissue. We evaluated the performance of a novel MRI technique, restriction spectrum imaging (RSI-MRI), to quantitatively detect and grade PCa compared with current standard-of-care MRI.
In a retrospective evaluation of 33 patients with biopsy-proven PCa who underwent RSI-MRI and standard MRI before radical prostatectomy, receiver-operating characteristic (ROC) curves were performed for RSI-MRI and each quantitative MRI term, with area under the ROC curve (AUC) used to compare each term's ability to differentiate between PCa and normal prostate. Spearman rank-order correlations were performed to assess each term's ability to predict PCa grade in the radical prostatectomy specimens.
RSI-MRI demonstrated superior differentiation of PCa from normal tissue, with AUC of 0.94 and 0.85 for RSI-MRI and conventional diffusion MRI, respectively (P=0.04). RSI-MRI also demonstrated superior performance in predicting PCa aggressiveness, with Spearman rank-order correlation coefficients of 0.53 (P=0.002) and -0.42 (P=0.01) for RSI-MRI and conventional diffusion MRI, respectively, with tumor grade.
RSI-MRI significantly improves upon current noninvasive PCa imaging and may potentially enhance its diagnosis and characterization.
The aim of the study was to determine the percentage of individuals with neuropathic diabetic foot ulcers receiving good wound care who heal within a defined period of time.
We conducted a systematic ...review of the control groups of clinical trials that evaluated a treatment for diabetic neuropathic foot ulcers. The meta-analytic techniques used include an estimation of the weighted mean percentage healed by end point, an evaluation of the homogeneity of trials, and an estimate of the 95% CI of the grouped data. Grouped-data univariate and multivariate logistic regression was conducted to assess the impact of mean age, ulcer size, and duration on the percentage of ulcers healed at end point.
We found a total of 10 control groups meeting our criteria. Six control groups used 20 weeks as the end point for healing or nonhealing. For the six control arms with a 20-week end point, we found a weighted mean healing rate of 30.9% (95% CI 26.6-35.1). A similar analysis for the four 12-week arms found a mean healing rate of 24.2% (19.5-28.8). We failed to detect any statistically significant heterogeneity for either the 20-week or the 12-week trials.
After 20 weeks of good wound care, approximately 31% of diabetic neuropathic ulcers heal. Similarly, after 12 weeks of good care, approximately 24% of neuropathic ulcers attain complete healing. Further patient-level analyses are necessary to definitively determine the associations of age, wound size, and wound duration with likelihood of healing.
Atopic dermatitis is a chronic, pruritic inflammatory dermatosis that affects up to 25% of children and 2% to 3% of adults. This guideline addresses important clinical questions that arise in atopic ...dermatitis management and care, providing recommendations based on the available evidence. In this third of 4 sections, treatment of atopic dermatitis with phototherapy and systemic immunomodulators, antimicrobials, and antihistamines is reviewed, including indications for use and the risk-benefit profile of each treatment option.
Companies are increasingly asked to provide innovative solutions to deep-seated problems of human misery, even as economic theory instructs managers to focus on maximizing their shareholders' wealth. ...In this paper, we assess how organization theory and empirical research have thus far responded to this tension over corporate involvement in wider social life. Organizational scholarship has typically sought to reconcile corporate social initiatives with seemingly inhospitable economic logic. Depicting the hold that economics has had on how the relationship between the firm and society is conceived, we examine the consequences for organizational research and theory by appraising both the 30-year quest for an empirical relationship between a corporation's social initiatives and its financial performance, as well as the development of stakeholder theory. We propose an alternative approach, embracing the tension between economic and broader social objectives as a starting point for systematic organizational inquiry. Adopting a pragmatic stance, we introduce a series of research questions whose answers will reveal the descriptive and normative dimensions of organizational responses to misery.
Standard magnetic resonance imaging (MRI) of the prostate lacks sensitivity in the diagnosis and staging of prostate cancer (PCa). To improve the operating characteristics of prostate MRI in the ...detection and characterization of PCa, we developed a novel, enhanced MRI diffusion technique using restriction spectrum imaging (RSI-MRI).
We compared the efficacy of our novel RSI-MRI technique with standard MRI for detecting extraprostatic extension (EPE) among 28 PCa patients who underwent MRI and RSI-MRI prior to radical prostatectomy, 10 with histologically proven pT3 disease. RSI cellularity maps isolating the restricted isotropic water fraction were reconstructed based on all b-values and then standardized across the sample with z-score maps. Distortion correction of the RSI maps was performed using the alternating phase-encode technique.
27 patients were evaluated, excluding one patient where distortion could not be performed. Preoperative standard MRI correctly identified extraprostatic the extension in two of the nine pT3 (22%) patients, whereas RSI-MRI identified EPE in eight of nine (89%) patients. RSI-MRI correctly identified pT2 disease in the remaining 18 patients.
In this proof of principle study, we conclude that our novel RSI-MRI technology is feasible and shows promise for substantially improving PCa imaging. Further translational studies of prostate RSI-MRI in the diagnosis and staging of PCa are indicated.
Despite the extraordinary success of HIV-1 antiretroviral therapy in prolonging life, infected individuals face lifelong therapy because of a reservoir of latently-infected cells that harbor ...replication competent virus. Recently, compounds have been identified that can reverse HIV-1 latency in vivo. These latency- reversing agents (LRAs) could make latently-infected cells vulnerable to clearance by immune cells, including cytolytic CD8+ T cells. We investigated the effects of two leading LRA classes on CD8+ T cell phenotype and function: the histone deacetylase inhibitors (HDACis) and protein kinase C modulators (PKCms). We observed that relative to HDACis, the PKCms induced much stronger T cell activation coupled with non-specific cytokine production and T cell proliferation. When examining antigen-specific CD8+ T cell function, all the LRAs except the HDACi Vorinostat reduced, but did not abolish, one or more measurements of CD8+ T cell function. Importantly, the extent and timing of these effects differed between LRAs. Panobinostat had detrimental effects within 10 hours of drug treatment, whereas the effects of the other LRAs were observed between 48 hours and 5 days. These observations suggest that scheduling of LRA and CD8+ T cell immunotherapy regimens may be critical for optimal clearance of the HIV-1 reservoir.
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