Purpose HIV-related diffuse large B-cell lymphoma (DLBCL) may be biologically different from DLBCL in the general population. We compared, by HIV status, the expression and prognostic significance of selected oncogenic markers in DLBCL diagnosed at Kaiser Permanente in California, between 1996 and 2007. Experimental Design Eighty HIV-infected DLBCL patients were 1:1 matched to 80 HIV-uninfected DLBCL patients by age, gender, and race. Twenty-three markers in the following categories were examined using IHC: (i) cell-cycle regulators, (ii) B-cell activators, (iii) antiapoptotic proteins, and (iv) others, such as IgM. Tumor marker expression was compared across HIV infection status by Fisher exact test. For markers differentially expressed in HIV-related DLBCL, logistic regression was used to evaluate the association between tumor marker expression and 2-year overall mortality, adjusting for International Prognostic Index, cell-of-origin phenotype, and DLBCL morphologic variants. Results Expression of cMYC (% positive in HIV-related and -unrelated DLBCL: 64% vs. 32%), BCL6 (45% vs. 10%), PKC-β2 (61% vs. 4%), MUM1 (59% vs. 14%), and CD44 (87% vs. 56%) was significantly elevated in HIV-related DLBCLs, whereas expression of p27 (39% vs. 75%) was significantly reduced. Of these, cMYC expression was independently associated with increased 2-year mortality in HIV-infected patients [relative risk = 3.09 (0.90–10.55)] in multivariable logistic regression. Conclusion These results suggest that HIV-related DLBCL pathogenesis more frequently involves cMYC and BCL6 among other factors. In particular, cMYC-mediated pathogenesis may partly explain the more aggressive clinical course of DLBCL in HIV-infected patients.

The accuracy of smoking history documentation in the electronic medical records was examined at a large managed care organization among 36,494 male members who self-reported smoking history in mailed surveys. The sensitivity of electronic smoking history documentation for ever-smoking status was 0.19 in years 2003-2005 (using ICD-9/CPT code only), 0.80 in 2006-2008 and 0.84 in 2009-2010 (combination of ICD-9/CPT codes and risk factor module used after 2006). The positive predictive value was 0.96, 0.90, and 0.95 in these periods, respectively. Among self-reported ever-smokers, increased healthcare utilization and smoking intensity/duration were associated with higher likelihood of having electronic smoking history documentation, while Asian race and Spanish language preference were associated with lower likelihood. These data suggest that enhanced efforts may be needed to screen for and document smoking among racial/ethnic minorities.

BackgroundRandomized studies of implantable cardioverter defibrillators (ICD) have excluded sudden cardiac death survivors who had revascularization before or after an arrhythmic event. To evaluate the role of ICD and the effects of clinical variables including degree of revascularization, we studied cardiac surgery patients who had an ICD implanted for sustained perioperative ventricular arrhythmias.Methods and ResultsThe electronic database for Southern California Kaiser Foundation hospitals was searched for patients who had cardiac surgery between 1999 and 2005 and an ICD implanted within 3 months of surgery. One hundred sixty‐four patients were identified; 93/164 had an ICD for sustained pre‐ or postoperative ventricular tachycardia or fibrillation requiring resuscitation. Records were reviewed for the following: presenting arrhythmia, ejection fraction, and degree of revascularization. The primary end point was total mortality (TM) and/or appropriate ICD therapy (ICD‐T), and secondary end points are TM and ICD‐T. During the mean follow up of 49 months, the primary endpoint of TM+ICD‐T and individual end points of TM and ICD‐T were observed in 52 (56%), 35 (38%), and 28 (30%) patients, respectively, with 55% of TM, and 23% of ICD‐T occurring within 2 years of implant. In multivariate risk analysis, none of the following was associated with any of the end points: incomplete revascularization, presenting ventricular arrhythmia, and timing of arrhythmias.ConclusionOur data supports the recent guidelines for ICD in this cohort of patients, as the presence of irreversible substrate and triggers of ventricular arrhythmias, cannot be reliably excluded even with complete revascularization. Further studies are needed to understand this complex group of patients.

Existing prognostic tools for HIV + diffuse large B-cell lymphoma (DLBCL) fail to accurately predict patient outcomes. To develop a novel prognostic algorithm incorporating molecular tumor characteristics and HIV disease factors, we included 80 patients with HIV-related DLBCL diagnosed between 1996 and 2007. Immunohistochemistry staining was used to analyze the expression of 26 tumor markers. Clinical data were collected from medical records. Logistic regression and bootstrapping were used to select and assess stability of the prognostic model, respectively. Of the tumor markers examined, expression of cMYC, Ki 67, CD44, EBV, SKP2, BCL6, p53, CD20 and IgM were associated with two-year mortality. The final prognostic model, confirmed in bootstrapped samples, included IPI, circulating CD4 cell count, history of clinical AIDS, and expression of CD44, p53, IgM and EBV. This model incorporating HIV disease history and tumor markers, achieved better prediction for two-year mortality [AUC = 0.87, 95% CI: 0.78-0.96] compared with IPI alone [AUC = 0.63 (0.51-0.75)].

Purpose Sleep problems are more common in breast cancer survivors than those without a cancer history. Our goal was to examine the risk of fractures among breast cancers survivors who used prescription sleep aids. Methods We conducted a retrospective cohort study of 21,346 adult women diagnosed with stage 0–III breast cancer between 2009 and 2016 and followed them through 2017. We examined person-year rates of fractures by sleep medication use and calculated adjusted hazard ratios (HR) and 95% confidence intervals (CI) with Cox proportional hazards models using time-dependent variables for sleep medications and covariate medications (antidepressants, anti-anxiety medications, and bisphosphonates) adjusted for demographics, comorbidities, and tumor characteristics and cancer treatments. Results The sleep medication use was common (40%) in breast cancer survivors and was associated with a 33% increased risk of fractures (adjusted HR = 1.33, 95% CI: 1.20–1.49). Further, in a sensitivity analysis based on new use of sleep medication, the fracture risk was even stronger (adjusted HR = 1.44, 95% CI: 1.26–1.64). Conclusion Given the high use of sleep medications and the high risk of fractures in breast cancer survivors, this study suggests that non-pharmacologic management of sleep problems might be considered as alternative therapy.