Genomic testing and molecular diagnosis among infants with congenital heart disease in the neonatal intensive care unit.

OBJECTIVE: To evaluate patterns of genetic testing among infants with CHD at a tertiary care center. STUDY DESIGN: We conducted a retrospective observational cohort study of infants in the NICU with suspicion of a genetic disorder. 1075 of 7112 infants admitted to BCH had genetic evaluation including 329 with CHD and 746 without CHD. 284 of 525 infants with CHD admitted to CMHH had genetic evaluation. Patterns of testing and diagnoses were compared. RESULTS: The rate of diagnosis after testing was similar for infants with or without CHD (38% [121/318] vs. 36% [246/676], p = 0.14). In a multiple logistic regression, atrioventricular septal defects were most high associated with genetic diagnosis (odds ratio 29.99, 95% confidence interval 2.69-334.12, p < 0.001). CONCLUSIONS: Infants with suspicion of a genetic disorder with CHD had similar rates of molecular diagnosis as those without CHD. These results support a role for genetic testing among NICU infants with CHD.

Modeling of global skin aging indices among Caucasian and Asian women.

BACKGROUND: The skin aging process is defined as the gradual degradation of several skin properties such as firmness, color, or the appearance of wrinkles. These properties can be assessed by trained experts, who perform an overall evaluation of the entire face. OBJECTIVE: The objective of this paper is the construction of two Global Skin Aging Indices specifically designed to model the overall skin aging process of Caucasian and Asian women. METHODS: Two hundred forty Asian women and 129 Caucasian women aged between 20 and 60 years old are recruited. Parameters related to wrinkles, sagging, elasticity, and skin tone are measured (clinically or instrumentally). The global skin aging index is defined as the normalized projection on the first principal component of a principal component analysis of the skin measurements. Then, linear regressions are performed between the indices and age of both panels. RESULTS: The first principal component carries around 50% of the initial variance for both indices. Both Global Skin Aging Indices statistically correlate with age (R2 ≥ 0.7, p-value < 0.05). An equation linking the indices with age is computed. CONCLUSION: The proposed indices are good indicators of the overall aging process for Caucasian and Asian women. They offer new approaches to assess antiaging product efficacy.

Treatment outcomes with purine nucleoside analog alone or with rituximab for hairy cell leukemia at first relapse.

INTRODUCTION: Frontline treatment of hairy cell leukemia (HCL) with a single course of the purine nucleoside analog (PNA) produces a high rate of complete remission (CR) with prolonged durations. At the time of relapse, although treatment guidelines recommend re-treatment with a PNA alone or in combination with rituximab (R), practice patterns vary and data supporting each approach are limited. METHODS: We conducted a multisite outcomes analysis of patients treated for HCL between 1995 and 2018 at six US medical centers. All patients were treated with frontline PNA and subsequently required treatment with a PNA alone (PNA) or with R (+R). RESULTS: Of the 88 patients analyzed, 56 (63.6%) received second-line PNA and 22 (36.4%) received a PNA + R. Baseline characteristics of both groups were similar. There was no difference in median PFS [67 months (95% CI 43.8 non-reached (NR)) vs. 65 months (95% CI 60-NR)] or 5-year OS [98% (95% CI 0.94-1) vs. 94% (95% CI 0.83-1), p = .104] in the PNA versus PNA + R cohorts, respectively. CONCLUSION: To our knowledge, this is the largest study evaluating the role of R in treatment of relapsed HCL and suggests that there is no advantage to the addition of R to PNA therapy at the time of first re-treatment.

Multicenter analysis of geriatric fitness and real-world outcomes in older patients with classical Hodgkin lymphoma.

We performed a multicenter retrospective analysis across 10 US academic medical centers to evaluate treatment patterns and outcomes in patients age ≥60 years with classic Hodgkin lymphoma (cHL) from 2010-2018. Among 244 eligible patients, median age was 68, 63% had advanced stage (III/IV), 96% had Eastern Cooperative Oncology Group performance status (PS) 0-2, and 12% had documented loss of ≥1 activity of daily living (ADL). Medical comorbidities were assessed by the Cumulative Illness Rating Scale-Geriatric (CIRS-G), where n = 44 (18%) had total scores ≥10. Using multivariable Cox models, only ADL loss predicted shorter progression-free (PFS; hazard ratio [HR] 2.13, P = .007) and overall survival (OS; HR 2.52, P = .02). Most patients (n = 203, 83%) received conventional chemotherapy regimens, including doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD; 56%), AVD (14%), and AVD with brentuximab vedotin (BV; 9%). Compared to alternative therapies, conventional regimens significantly improved PFS (HR 0.46, P = .0007) and OS (HR 0.31, P = .0003). Survival was similar following conventional chemotherapy in those ages 60-69 vs ≥70: PFS HR 0.88, P = .63; OS HR 0.73, P = .55. Early treatment discontinuation due to toxicity was more common with CIRS-G ≥10 (28% vs 12%, P = .016) or documented geriatric syndrome (28% vs 13%, P = .02). A competing risk analysis demonstrated improved disease-related survival with conventional therapy (HR 0.29, P = .02) and higher mortality from causes other than disease or treatment with high CIRS-G or geriatric syndromes. This study suggests conventional chemotherapy regimens remain a standard of care in fit older patients with cHL, and highlights the importance of geriatric assessments in defining fitness for cHL therapy going forward.

The Emerging Role of Minimal Residual Disease Testing in Diffuse Large B-Cell Lymphoma.

PURPOSE OF REVIEW: Diffuse large B cell lymphoma (DLBCL) is characterized by clinical heterogeneity that is not fully accounted for by pathologic features. Furthermore, real-time treatment modifications and detection of relapse are typically guided by radiographic imaging modalities which are imperfect. Here, we review the potential utility of minimal residual disease (MRD) assessment for informing treatment decisions and detecting relapse. RECENT FINDINGS: The most promising method of MRD detection is based on analysis of circulating tumor DNA in the peripheral blood of patients with DLBCL. This approach can predict outcomes and response to treatment as well as detect relapse prior to clinical signs of recurrent disease. While some studies of MRD in DLBCL have been in the prospective setting, the ability of this technology to alter clinical outcomes is currently unknown. MRD detection provides a non-invasive way to gather information about DLBCL at various time points throughout the disease course. Its role is evolving and should be incorporated into prospective studies in order to demonstrate an impact on patient outcomes.

Prostate-specific antigen response in black and white patients treated with abiraterone acetate for metastatic castrate-resistant prostate cancer.

PURPOSE: Evidence suggests differences in androgen receptor AR signaling between black (B) and white (W) patients with prostate cancer, but pivotal trials of abiraterone acetate (AA) for patients with metastatic castration-resistant prostate cancer (mCRPC) enrolled few black patients, a population with a higher mortality from prostate cancer. Our primary objective was to determine differences in response to AA between B and W patients. METHODS: We performed a retrospective case-control study of B vs. W patients treated with AA between May 1, 2008 and June 16, 2015 at Duke University Medical Center. Patients were identified (W control patients were matched 2:1 to B patients stratified based on previous docetaxel exposure) through pharmacy records and were eligible if treated with AA for metastatic castration-resistant prostate cancer. Patients with previous enzalutamide use were excluded. The primary objective was to compare the rate of≥90% prostate-specific antigen (PSA) decline from baseline between B vs. W patients. Secondary outcomes included comparing time on therapy, time to PSA progression, and overall survival among groups. RESULTS: Baseline characteristics among patients (n = 45 B, n = 90 W) were identified; these included Karnofsky performance status, PSA, Gleason score, alkaline phosphatase, albumin, hemoglobin, lactate dehydrogenase, opiate use for pain, and metastatic sites. Baseline characteristics among groups were similar except for median hemoglobin (B = 11.4g/dl, W = 12.3g/dl). The proportion of B patients achieving a≥90% PSA level decline was 37.8% vs. 28.9% for W patients (P = 0.296). Statistically significant differences were found in the proportion of patients achieving a≥50% PSA level decline (B = 68.9%, W = 48.9% [P = 0.028]) and≥30% PSA level decline (B = 77.8%, W = 54.4% [P = 0.008]). Rates of primary abiraterone-refractory disease (PSA increase as best response) trended higher in W (31.1%) than in B (15.6%) patients (P = 0.052). Median treatment duration (B = 9.4 mo, W = 8.3 mo) did not differ (Wilcoxon P = 0.444). Median overall survival (B = 27.3 mo [95% CI: 13.9, not estimable], W = 24.8 mo [95% CI: 19, 31.6] [P = 0.669]) and median time to PSA progression (B = 11.0 mo [95% CI: 4.3, 18.0], W = 9.4 mo [95% CI: 6.2, 13.0] [P = 0.917]) did not differ. CONCLUSIONS: Black patients may have a higher PSA response to AA than white patients. An ongoing prospective clinical study (NCT01940276) is evaluating outcomes between black and white patients treated with AA.

What is the role of sipuleucel-T in the treatment of patients with advanced prostate cancer? An update on the evidence.

Prostate cancer is the most common cancer in men and the second most deadly. About one-third of patients with prostate cancer will develop metastatic disease. We discuss the six United States Food and Drug Administration (FDA) approved treatments for metastatic castrate-resistant prostate cancer (mCRPC) with a strong focus on sipuleucel-T. Sipuleucel-T is the first immunotherapy shown to improve survival in asymptomatic or minimally-symptomatic mCRPC. Herein, we discuss the proposed mechanism of sipuleucel-T and its synthesis. We describe in detail the three randomized controlled trials (RTCs) that led to its approval. We also compiled the newest research regarding use of sipuleucel-T with other agents and in different patient populations. Finally, we discuss the current ongoing trials.