Metabolic biomarkers assessed with PET/CT predict sex-specific longitudinal outcomes in patients with diffuse large B-cell lymphoma

In many cancers, including lymphoma, males have higher incidence and mortality than females. Emerging evidence demonstrates that one mechanism underlying this phenomenon is sex differences in metabolism, both with respect to tumor nutrient consumption and systemic alterations in metabolism, i.e., obesity. We wanted to determine if visceral fat and tumor glucose uptake with fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) could predict sex-dependent outcomes in patients with diffuse large B-cell lymphoma (DLBCL). We conducted a retrospective analysis of 160 patients (84 males; 76 females) with DLBCL who had imaging at initial staging and after completion of therapy. CT-based relative visceral fat area (rVFA), PET-based SUVmax normalized to lean body mass (SULmax), and end-of-treatment FDG-PET 5PS score were calculated. Increased rVFA at initial staging was an independent predictor of poor OS only in females. At the end of therapy, increase in visceral fat was a significant predictor of poor survival only in females. Combining the change in rVFA and 5PS scores identified a subgroup of females with visceral fat gain and high 5PS with exceptionally poor outcomes. These data suggest that visceral fat and tumor FDG uptake can predict outcomes in DLBCL patients in a sex-specific fashion

Determinants of Default from Tuberculosis Treatment among Patients with Drug-Susceptible Tuberculosis in Karachi, Pakistan: A Mixed Methods Study

<div><p>Purpose</p><p>Non-adherence to tuberculosis therapy can lead to drug resistance, prolonged infectiousness, and death; therefore, understanding what causes treatment default is important. Pakistan has one of the highest burdens of tuberculosis in the world, yet there have been no qualitative studies in Pakistan that have specifically examined why default occurs. We conducted a mixed methods study at a tuberculosis clinic in Karachi to understand why patients with drug-susceptible tuberculosis default from treatment, and to identify factors associated with default. Patients attending this clinic pick up medications weekly and undergo family-supported directly observed therapy.</p><p>Methods</p><p>In-depth interviews were administered to 21 patients who had defaulted. We also compared patients who defaulted with those who were cured, had completed, or had failed treatment in 2013.</p><p>Results</p><p>Qualitative analyses showed the most common reasons for default were the financial burden of treatment, and medication side effects and beliefs. The influence of finances on other causes of default was also prominent, as was concern about the effect of treatment on family members. In quantitative analysis, of 2120 patients, 301 (14.2%) defaulted. Univariate analysis found that male gender (OR: 1.34, 95% CI: 1.04–1.71), being 35–59 years of age (OR: 1.54, 95% CI: 1.14–2.08), or being 60 years of age or older (OR: 1.84, 95% CI: 1.17–2.88) were associated with default. After adjusting for gender, disease site, and patient category, being 35–59 years of age (aOR: 1.49, 95% CI: 1.10–2.03) or 60 years of age or older (aOR: 1.76, 95% CI: 1.12–2.77) were associated with default.</p><p>Conclusions</p><p>In multivariate analysis age was the only variable associated with default. This lack of identifiable risk factors and our qualitative findings imply that default is complex and often due to extrinsic and medication-related factors. More tolerable medications, improved side effect management, and innovative cost-reduction measures are needed to reduce default from tuberculosis treatment.</p></div

Themes with related categories and inductive codes.

<p>TB = tuberculosis</p><p>Themes with related categories and inductive codes.</p

Multivariate analysis of sociodemographic and clinical variables associated with default.^*

<p>*1998 patients; excludes patients who died, transferred out, or had a change in diagnosis</p><p>TB = tuberculosis; CAT = treatment class; CAT-1 = first treatment with first-line drugs; CAT-2 = retreatment with first-line drugs</p><p>Multivariate analysis of sociodemographic and clinical variables associated with default.^{<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0142384#t005fn001" target="_blank">*</a>}</p

Univariate analysis of sociodemographic and clinical variables associated with default.^*

<p>*1998 patients; excludes patients who died, transferred out, or had a change in diagnosis</p><p>TB = tuberculosis; CAT = treatment class; CAT-1 = first treatment with first-line drugs; CAT-2 = retreatment with first-line drugs</p><p>Univariate analysis of sociodemographic and clinical variables associated with default.^{<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0142384#t004fn001" target="_blank">*</a>}</p

Demographic and clinical characteristics of study population.

<p>*Smear status available for 951 patients with pulmonary TB</p><p>TB = tuberculosis; CAT = treatment class; CAT-1 = first treatment with first-line drugs; CAT-2 = retreatment with first-line drugs; Intensive phase = first 2 months of treatment; Continuation phase = 4–6 months of treatment following the first 2 months of treatment</p><p>Demographic and clinical characteristics of study population.</p

Examples of in-depth interview questions (English translations).

<p>TB = tuberculosis</p><p>Examples of in-depth interview questions (English translations).</p