Citations

Abstract An enhanced understanding of the molecular heterogeneity of diffuse large B-cell lymphoma (DLBCL) has opened the door to clinical trials evaluating novel agents with subtype-specific activity. It is an emerging question whether core needle biopsies (CNB) can adequately meet the increasing tissue requirements of these clinical trials. This can potentially lead to selective enrollment of patients who can undergo excisional biopsy (EB). It is also important to know whether patients who can undergo extensive diagnostic work up differ in their disease characteristics and outcomes from those who cannot. In this observational study, we describe the characteristics, outcomes, and adequacy of diagnostic tissue in patients with newly diagnosed DLBCL and primary mediastinal large B-cell lymphoma who underwent EB vs CNB. Of the 1061 patients, 532 (49.8%) underwent EB and 529 (50.1%) underwent CNB. A significantly higher proportion of patients with CNB had advanced stage disease, an international prognostic index of ≥3, and inadequate tissue for molecular analyses. Patients with CNB had significantly worse 5-year event-free survival (67.6% vs 56.9%; hazard ratio [HR], 0.76; confidence interval [CI]95, 0.6-0.9, P < .001) and 5-year overall survival (76.4% vs 69.2%; HR, 0.8; CI95, 0.6-0.9, P < .001). Thus, patients who underwent CNB have poor-risk features and inferior outcomes on frontline chemoimmunotherapy, are more likely to have inadequate tissue for molecular analyses, and might not meet the tissue requirements of biomarker-driven clinical trials. Thus, the increasing tissue requirements of biomarker-driven clinical trials may result in the exclusion of patients with high-risk DLBCL who need novel agents.

Abstract Background Opioids are frequently prescribed to alleviate pain in older adults, yet the relationships between prescription opioids and long‐term cognitive function are unclear. Methods In this analysis of the Mayo Clinic Study of Aging, a longitudinal population‐based cohort study of older adults with formal neuropsychological testing and cognitive evaluations performed every 15 months, the associations between prescription opioids, global and domain‐specific cognitive function, and mild cognitive impairment were evaluated through time‐dependent linear mixed effects and Cox proportional hazards models. Results Four thousand two hundred eighteen participants (51% male) were included with enrollment between 11/1/2004 and 4/1/2019 and median age of 76 (interquartile range 72, 82) years. Two thousand nine hundred seventy‐seven subjects (71%) received at least 1 opioid prescription during a median follow‐up of 7.5 (5.0, 10.7) years. Overall, there was an estimated 0.096 reduction in the global cognitive Z ‐score per year, including decreases of 0.050 in memory, 0.080 in language, 0.044 in visual–spatial cognition, and 0.112 in attention. In multivariable analyses, each receipt of an opioid prescription resulted in an additional −0.007 (95% CI −0.009, −0.005) change in global cognitive Z ‐score ( p < 0.001), with significant effects seen in the domains of memory (−0.005, 95% CI −0.007, −0.003; p < 0.001), language (−0.002, 95% CI −0.003, 0.000; p = 0.024) and attention (−0.004, 95% CI −0.006, −0.002; p < 0.001) but not visual–spatial function (0.000, 95% CI −0.001, 0.001; p = 0.897). Opioid prescriptions were associated with incident mild cognitive impairment (MCI) in adjusted analysis (hazard ratio 1.21, 95% CI 1.04, 1.42; p = 0.014). Conclusion Prescription opioids are associated with small but statistically significant declines in long‐term cognitive function in older adults, which may represent effects of opioids or other related factors.

AbstractExtranodal marginal zone lymphoma (EMZL) is a heterogeneous disease with a subset of patients exhibiting a more aggressive course. We previously reported that EMZL with multiple mucosal sites (MMS) at diagnosis is characterized by shorter survival. To better recognize patients with different patterns of progression‐free survival (PFS) we developed and validated a new prognostic index primarily based on patient's disease characteristics. We derived the “Revised mucosa‐associated lymphoid tissue International Prognostic Index” (Revised MALT‐IPI) in a large data set (n = 397) by identifying candidate variables that showed highest prognostic association with PFS. The revised MALT‐IPI was validated in two independent cohorts, from the University of Iowa/Mayo Clinic (n = 297) and from IELSG‐19 study (n = 400). A stepwise Cox regression analysis yielded a model including four independent predictors of shorter PFS. Revised MALT‐IPI has scores ranging from 0 to 5, calculated as a sum of one point for each of the following‐ age >60 years, elevated LDH, and stage III–IV; and two points for MMS. In the training cohort, the Revised MALT‐IPI defined four risk groups: low risk (score 0, reference group), low‐medium risk (score 1, HR = 1.85, p = .008), medium‐high risk (score 2, HR = 3.84, p < .0001), and high risk (score 3+, HR = 8.48, p < .0001). Performance of the Revised MALT‐IPI was similar in external validation cohorts. Revised MALT‐IPI is a new index centered on disease characteristics that provides robust risk‐stratification identifying a group of patients characterized by earlier progression of disease. Revised MALT‐IPI can allow a more disease‐adjusted management of patients with EMZL in clinical trials and practice.

AbstractNon‐Hodgkin lymphoma (NHL) is composed of a heterogeneous collection of subtypes with considerable differences in genetics, biology and aetiology. Studies to date on physical activity and NHL risk have not had sufficient sample size to evaluate whether associations differ by subtype. We pooled data from nine case‐control studies to examine the association between moderate‐to‐vigorous intensity physical activity (MVPA) and risk of NHL overall and by subtype (diffuse large B‐cell lymphoma, follicular lymphoma, chronic lymphocytic leukaemia/small lymphocytic lymphoma, marginal zone lymphoma and mature T‐cell lymphoma). A total of 5653 cases and 9115 controls were included in the pooled analysis. Physical activity was harmonised across nine studies and modelled as study‐specific tertiles. Multinomial logistic regression was used to estimate the association between physical activity and NHL, adjusting for confounders. The overall odds of NHL was 13% lower among participants in the most active tertile of MVPA compared to the least active tertile (adjusted odds ratio = 0.87, 95% CI = 0.80, 0.95). Similar decreases were observed across NHL subtypes. In summary, in this pooled analysis of case‐control studies, physical activity was associated with a modest risk reduction for each NHL subtype examined and with overall NHL.

Objective: To compare patient-reported outcomes before and after implementation of evidence-based, procedure-specific opioid prescribing guidelines. Background: The opioid epidemic remains a significant public health issue. Many institutions have responded by reducing opioid prescribing after surgery. However, the impact of this on patient-reported outcomes remains poorly understood. Methods: Opioid-naïve adults undergoing 12 elective general surgery procedures at a single institution prospectively completed telephone surveys at median 26 days from discharge. Patients were compared before (March 2017–January 2018) and after (May 2019–November 2019) implementation of evidence-based, procedure-specific opioid prescribing guidelines. Results: A total of 603 preguideline and 138 postguideline patients met inclusion criteria and completed surveys. Overall, 60.5% of preguideline and 92.5% of postguideline prescriptions fell within recommendations (P<0.001), while refill rates were similar (4.5% vs 5.8%, P=0.50). A statistically significant drop in median morphine milligram equivalent prescribed was observed for 9 of 12 procedures (75%). No opioids were prescribed for 16.7% of patients in both cohorts (P=0.98). While 93.3% of preguideline and 87.7% of postguideline patients were very/somewhat satisfied with their pain control, the proportion of patients who were very/somewhat dissatisfied increased from 4.2% to 9.4% (P=0.039). Conclusions: Prescribing guidelines successfully reduced opioid prescribing without increased refill rates. Despite decreased prescribing overall, there was a continued reluctance to prescribe no opioids after surgery. Although most patients experienced good pain control, there remains a subset of patients whose pain is not optimally managed in the era of reduced opioid prescribing.

AbstractChronic pain is highly prevalent in older adults and is associated with poor functional outcomes. Furthermore, opioid analgesics are commonly utilized for the treatment of pain in older adults despite well-described adverse effects. Importantly, both chronic pain and opioid analgesics have been linked with impairments in cognitive function, though data are limited. In this manuscript we summarize the evidence and critical knowledge gaps regarding the relationships between pain, opioid analgesics, and cognition in older adults. Furthermore, we provide a conceptual framework to guide future research in the development, implementation, and evaluation of strategies to optimize analgesic outcomes in older adults while minimizing deleterious effects on cognition.