Chronic Pain Management in the Elderly.

Chronic pain is extremely prevalent in older adults and is associated with significant morbidity, including limited mobility, social isolation, and depressed mood. Pain is defined by a biopsychosocial model highlighting the importance of a multidisciplinary approach to treatment, including multimodal medications, selected interventions, physical therapy and rehabilitation, and psychological treatments. In this narrative review, the authors highlight the use of these approaches in older adults with specific attention paid to considerations unique to aging, including alterations in drug metabolism, avoidance of polypharmacy, and physiologic changes predisposing to painful conditions.

Combining a GSI and BCL-2 inhibitor to overcome melanoma's resistance to current treatments.

Major limitations of current melanoma treatments are for instances of relapse and the lack of therapeutic options for BRAF wild-type patients who do not respond to immunotherapy. Many studies therefore focus on killing resistant subpopulations, such as Melanoma Initiating Cells (MICs) to prevent relapse. Here we examined whether combining a GSI (γ-Secretase Inhibitor) with ABT-737 (a small molecule BCL-2/BCL-XL/BCL-W inhibitor) can kill both the non-MICs (bulk of melanoma) and MICs. To address the limitations of melanoma therapies, we included multiple tumor samples of patients relapsed from current treatments, with a diverse genetic background (with or without the common BRAF, NRAS or NF1 mutations) in these studies. Excitingly, the combination treatment reduced cell viability and induced apoptosis of the non-MICs; disrupted primary spheres, decreased the ALDH+ cells, and inhibited the self-renewability of the MICs in multiple melanoma cell lines and relapsed patient samples. Using a low-cell-number mouse xenograft model, we demonstrated that the combination significantly reduced the tumor initiating ability of MIC-enriched cultures from relapsed patient samples. Mechanistic studies also indicate that cell death is NOXA-dependent. In summary, this combination may be a promising strategy to address treatment relapse and for triple wild-type patients who do not respond to immunotherapy.

Alternative Treatments For Melanoma: Targeting BCL-2 Family Members to De-Bulk and Kill Cancer Stem Cells.

For the first time new treatments in melanoma have produced significant responses in advanced diseases, but 30-90% of melanoma patients do not respond or eventually relapse after the initial response to the current treatments. The resistance of these melanomas is likely due to tumor heterogeneity, which may be explained by models such as the stochastic, hierarchical, and phenotype-switching models. This review will discuss the recent advancements in targeting BCL-2 family members for cancer treatments, and how this approach can be applied as an alternative option to combat melanoma, and overcome melanoma relapse or resistance in current treatment regimens.

How should unmatched otolaryngology applicants proceed?

OBJECTIVES/HYPOTHESIS: To determine the attitudes of otolaryngology residency program directors and chairpersons toward unmatched residency applicants, including whether a surgical internship or research year is preferred in considering repeat applicants. STUDY DESIGN: Cross-sectional survey. METHODS: Approval was obtained from the Colorado Multiple Institution Review Board. A 12-question Web-based survey was sent to otolaryngology residency program directors and chairpersons three times over a 6-week period. Responses collected from respondents were anonymous, with no identifying characteristics. RESULTS: Forty-five percent of those contacted responded to the survey. The most commonly recommended course of action for an unmatched applicant was completion of a general surgery intern year (43%) or a year of research (31%). Program directors were more likely than chairpersons to recommend a year of research (P value 0.014). Ninety-seven percent of the respondents felt it was important or essential to obtain new letters of recommendation. Respondents ranked poor interview skills as the most common reason for applicants remaining unmatched (29%). CONCLUSION: Otolaryngology residency match is even more competitive for previously unmatched applicants. Unmatched applicants should be advised to proceed with either a research year or postgraduate year 1 general surgery year. Before applying again, applicants should obtain new letters of recommendation, and the importance of improving poor interviewing skills should be emphasized by advisors. LEVEL OF EVIDENCE: N/A.