Publications

PURPOSE

To evaluate the success rate of CT-guided bone biopsies in metastatic castration-resistant prostate cancer (mCRPC) and to investigate associated technical, imaging, and clinical parameters affecting diagnostic yields.

MATERIALS AND METHODS

Eighty CT-guided bone biopsy specimens were obtained from 72 men (median age, 68 y; range, 49-89 y) enrolled in a multicenter trial to identify mechanisms of resistance in mCRPC. Successful biopsy was determined by histologic confirmation of tumor cells and successful isolation of RNA for molecular analysis.

RESULTS

The overall success rate of CT-guided bone biopsies was 69% (55/80) based on histology and 64% (35/55) based on isolation of molecular material for RNA sequencing. Biopsies performed in lesions with areas of radiolucency had significantly higher diagnostic yields compared with lesions of predominantly dense sclerosis (95% vs 33%; P = .002) and lesions of predominantly subtle sclerosis (95% vs 65%; P = .04). Success rates increased in lesions with density ≤ 475 HU (79% for ≤ 475 HU vs 33% for > 475 HU; P = .001) and in lesions with ill-defined margins (76% for ill-defined margins vs 36% for well-circumscribed margins; P = .005). Alkaline phosphatase was the only clinical parameter to correlate significantly with diagnostic yield (83% for > 110 U/L vs 50% for ≤ 110 U/L; P = .001).

CONCLUSIONS

Image-guided bone tumor biopsies can be successfully used to acquire cellular and molecular material for analyses in patients with osteoblastic prostate cancer metastases. Diagnostic yields are significantly increased in lesions with areas of radiolucency, density ≤ 475 HU, ill-defined margins, and interval growth and in patients with alkaline phosphatase > 110 U/L.

BACKGROUND

Exercise-based cardiac rehabilitation (CR) is under-utilized. CR is indicated after heart transplantation, but there are no data regarding CR participation in transplant recipients. We characterized current CR utilization among heart transplant recipients in the United States and the association of CR with 1-year readmissions using the 2013-2014 Medicare files.

METHODS

The study population included Medicare beneficiaries enrolled due to disability (patients on the transplant list are eligible for disability benefits under Medicare regulations) or age ≥65 years. We identified heart transplant patients by diagnosis codes and cumulative CR sessions occurring within 1 year after the transplant hospitalization.

RESULTS

There were 2,531 heart transplant patients in the USA in 2013, of whom 595 (24%) received Medicare coverage and were included in the study. CR utilization was low, with 326 patients (55%) participating in CR programs. The Midwest had the highest proportion of transplant recipients initiating CR (68%, p = 0.001). Patients initiating CR attended a mean of 26.7 (standard deviation 13.3) sessions, less than the generally prescribed program of 36 sessions. Transplant recipients age 35 to 49 years were less likely to initiate CR (odds ratio [OR] 0.39, 95% confidence interval [CI] 0.23 to 0.66, p < 0.001) and attended 8.2 fewer sessions (95% CI 3.5 to 12.9, p < 0.001) than patients age ≥65 years. CR participation was associated with a 29% lower 1-year readmission risk (95% CI 13% to 42%, p = 0.001).

CONCLUSIONS

Only half of cardiac transplant recipients participate in CR, and those who do have a lower 1-year readmission risk. These data invite further study on barriers to CR in this population.

There is growing concern among US-based clinicians, patients, policy makers, and in the media about the personal and community health risks associated with opioids. Perceptions about the efficacy and appropriateness of opioids for the management of chronic non-cancer pain (CNCP) have dramatically transformed in recent decades. Yet, there is very little social scientific research identifying the factors that have informed this transformation from the perspectives of prescribing clinicians. As part of an on-going ethnographic study of CNCP management among clinicians and their patients with co-occurring substance use, we interviewed 23 primary care clinicians who practice in safety-net clinical settings. In this paper, we describe the clinical and social influences informing three historic periods: (1) the escalation of opioid prescriptions for CNCP; (2) an interim period in which the efficacy of and risks associated with opioids were re-assessed; and (3) the current period of "opioid pharmacovigilance," characterized by the increased surveillance of opioid prescriptions. Clinicians reported that interpretations of the evidence-base in favor of and opposing opioid prescribing for CNCP evolved within a larger clinical-social context. Historically, pharmaceutical marketing efforts and clinicians' concerns about racialized healthcare disparities in pain treatment influenced opioid prescription decision-making. Clinicians emphasized how patients' medical complexity (e.g. multiple chronic health conditions) and structural vulnerability (e.g. poverty, community violence) impacted access to opioids within resource-limited healthcare settings. This clinical-social history of opioid prescribing practices helps to elucidate the ongoing challenges of CNCP treatment in the US healthcare safety net and lends needed specificity to the broader, nationwide conversation about opioids.

Whether APOL1 polymorphisms contribute to the excess risk of hypertension among blacks is unknown. To assess this we evaluated whether self-reported race and, in blacks, APOL1 risk variants (high-risk [2 risk alleles] versus low-risk [0-1 risk allele]) were associated with longitudinal blood pressure. Blood pressure trajectories were determined using linear mixed-effects (slope) and latent class models (5 distinct groups) during 25 years of follow-up in the Coronary Artery Risk Development in Young Adults Study. Associations of race and APOL1 genotypes with blood pressure change, separately, using linear mixed-effects and multinomial logistic regression models, adjusting for demographic, socioeconomic, and traditional hypertension risk factors, anti-hypertensive medication use, and kidney function were evaluated. Among 1700 whites and 1330 blacks (13% APOL1 high-risk, mean age 25 years; 46% male) mean mid-, ([systolic + diastolic blood pressure]/2), systolic, and diastolic blood pressures were 89, 110, and 69 mm Hg, respectively. One percent of participants used anti-hypertensive medications at baseline. Compared to whites, blacks, regardless of APOL1 genotype, had significantly greater increases in mid-blood pressure and were more likely to experience significantly increasing mid-blood pressure trajectories with adjusted relative risk ratios of 5.21 and 7.27 for moderate-increasing and elevated-increasing versus low-stable blood pressure, respectively. Among blacks, longitudinal mid-blood pressure changes and mid-blood pressure trajectory classification were similar by APOL1 risk status. Modeling systolic and diastolic blood pressure as outcomes yielded similar findings. From young adulthood to mid-life, blacks have greater blood pressure increases versus whites that are not fully explained by traditional risk factors. Thus APOL1 variants are not associated with longitudinal blood pressure in blacks.

CD4 T cells differentiate into T helper cell subsets in feedforward manners with synergistic signals from the T cell receptor (TCR), cytokines, and lineage-specific transcription factors. Naive CD4 T cells avoid spontaneous engagement of feedforward mechanisms but retain a prepared state. T cells lacking the adaptor molecule LAT demonstrate impaired TCR-induced signals yet cause a spontaneous lymphoproliferative T helper 2 (T2) cell syndrome in mice. Thus, LAT constitutes an unexplained maintenance cue. Here, we demonstrate that tonic signals through LAT constitutively export the repressor HDAC7 from the nucleus of CD4 T cells. Without such tonic signals, HDAC7 target genes Nur77 and Irf4 are repressed. We reveal that Nur77 suppresses CD4 T cell proliferation and uncover a suppressive role for Irf4 in T2 polarization; halving Irf4 gene-dosage leads to increases in GATA3 and IL-4 cells. Our studies reveal that naive CD4 T cells are dynamically tuned by tonic LAT-HDAC7 signals.