Citations

ObjectiveFew data are available regarding the rates of serious adverse events (SAEs) and important medical events (IMEs) outside of product‐based registries and clinical trials for juvenile idiopathic arthritis (JIA). The Enhanced Drug Safety Surveillance Project (EDSSP) was developed to pilot a novel system to collect SAEs/IMEs in children with JIA. This analysis reports the results from this 4‐year (2008–2012) EDSSP.MethodsParticipating physicians were surveyed monthly to ascertain whether their JIA patients experienced an SAE or IME. Sites were surveyed every 6 months to determine the number of unique JIA patients seen at each site during that 6‐month period. Reporting rates were calculated per 100 person‐years and 95% confidence intervals (95% CIs) were calculated based on a Poisson distribution.ResultsThirty‐seven Childhood Arthritis and Rheumatology Research Alliance sites with 115 physicians participated. The mean response rate to the monthly surveys was 65%. There were 147 total SAEs and 145 total IMEs. The largest proportion of SAEs and IMEs occurred in children with polyarticular JIA (39% and 37%, respectively). The majority of SAEs and IMEs were reported for patients receiving therapy with biologic agents (76% and 69%, respectively). The total event rate for SAEs and IMEs combined was 1.07 events per 100 person‐years (95% CI 0.95–1.19). The rates for SAEs and IMEs were 0.54 per 100 person‐years (95% CI 0.45–0.63) and 0.53 per 100 person‐years (95% CI 0.49–0.62), respectively.ConclusionThe EDSSP provided a simple tool for SAE/IME reporting within an established research network and resulted in a similar range of reported events as captured by a traditional product‐based registry.

Green’s functions effectively simulate shear waves produced by an applied acoustic radiation force in elastic and viscoelastic soft tissue. In an effort to determine the optimal parameters for these simulations, the convergence of Green's function-based calculations is evaluated for realistic spatial distributions of the initial radiation force “push.” The input to these calculations is generated by FOCUS, the “Fast Object-oriented C + + Ultrasound Simulator,” which computes the approximate intensity fields generated by a Phillips L7-4 ultrasound transducer array for both focused and unfocused beams. The radiation force in the simulation model, which is proportional to the simulated intensity, is applied for 200 μs, and the resulting displacements are calculated with the Green's function model. Simulation results indicate that, for elastic media, convergence is achieved when the intensity field is sampled at roughly one-tenth of the wavelength of the compressional component that delivers the radiation force “push.” Aliasing and oscillation artifacts are observed in the model for an elastic medium at lower sampling rates. For viscoelastic media, spatial sampling rates as low as two samples per compressional wavelength are sufficient due to the low-pass filtering effects of the viscoelastic medium. [Supported in part by NIH Grants R01EB012079 and R01DK092255.]

In conventional shear wave elastography materials are assumed to be linear, elastic, homogeneous, and isotropic. These assumptions are important to account for in certain tissues because they are not always appropriate. Many tissues such as skeletal muscle, the kidney, and the myocardium are anisotropic. Shear waves can be used to investigate the directionally dependent mechanical properties of anisotropic media. To study these tissues in a systematic way and to account for the effects of the anisotropic architecture, laboratory-based phantoms are desirable. We will report on several phantom-based approaches for studying shear wave anisotropy, assuming that these materials are transversely isotropic. Phantoms with embedded fibers were used to mimic anisotropic tissues. Homogeneous phantoms were compressed to induce transverse isotropy according to the acoustoelastic phenomenon, which is related to nonlinear behavior of the materials. The fractional anisotropy of these phantoms was quantified to compare with measurements made in soft tissues. In addition, soft tissues are also viscoelastic, and we have developed a method to model viscoelastic transversely isotropic materials with the finite element method (FEM). The viscoelastic property estimation from phantom experiments and FEM simulations will also be discussed.

Abstract Therapies that activate the immune system through blocking the binding of programmed death ligand 1 (PD-L1) present on tumors and PD-1 (programmed death 1) present on activated immune cells are revolutionizing the care for patients with cancer. These therapies work by inhibiting negative regulators of the immune system, thereby decreasing a tumor's ability to evade the immune system. The side effects of anti–PD-1/PD-L1 therapies are generally mild and as expected are related to autoimmune reactions. Two of the most common side effects of anti–PD-1/PD-L1 therapies are rash and pruritus occurring in approximately 20% of patients. Although the rash is generally recognized to be immune mediated, the exact mechanisms of the rash remain unclear. Herein, we report three cases of lichenoid dermatitis in three patients treated with MK-3475 (anti–PD-1) that were characterized with marked T-cell infiltrates with few PD-1–positive cells. The rashes in all three patients were relatively mild, allowing treatment to continue despite the rashes. Cancer Immunol Res; 3(1); 18–22. ©2014 AACR.

ABSTRACT Central nervous system infection due to herpes simplex virus (HSV) is a medical emergency and requires rapid diagnosis and initiation of therapy. In this study, we compared a routine real-time PCR assay for HSV types 1 (HSV-1) and 2 (HSV-2) to a recently FDA-approved direct PCR assay (Simplexa HSV-1/2 Direct; Focus Diagnostics, Cypress, CA) using cerebrospinal fluid samples ( n = 100). The Simplexa HSV-1/2 assays demonstrated a combined sensitivity and specificity of 96.2% (50/52) and 97.9% (47/48), respectively. In addition, the Simplexa assay does not require nucleic acid extraction, and the results are available in 60 min.

Batracylin (NSC-320846) is a dual inhibitor of DNA topoisomerases I and II. Batracylin advanced as an anticancer agent to Phase I clinical trials where dose limiting hemorrhagic cystitis (bladder inflammation and bleeding) was observed. To further investigate batracylin’s mechanism of toxicity, studies were conducted in Fischer 344 rats. Once daily oral administration of 16 or 32 mg/kg batracylin to rats for 4 days caused overt toxicity. Abnormal clinical observations and adverse effects on clinical pathology, urinalysis, and histology indicated acute renal damage and urothelial damage and bone marrow dysfunction. Scanning electron microscopy revealed sloughing of the superficial and intermediate urothelial layers. DNA damage was evident in kidney and bone marrow as indicated by histone γ-H2AX immunofluorescence. After a single oral administration of 16 or 32 mg/kg, the majority of batracylin was converted to N-acetylbatracylin (NAB) with a half-life of 4 hr to 11 hr. Mesna (Mesnex™), a drug known to reduce the incidence of hemorrhagic cystitis induced by ifosfamide or cyclophosphamide, was administered to rats prior to batracylin, but did not alleviate batracylin-induced bladder and renal toxicity. These findings suggest that batracylin results in DNA damage-based mechanisms of toxicity and not an acrolein-based mechanism of toxicity as occurs after ifosfamide or cyclophosphamide administration.

Objective (1) To characterize long‐term dizziness following observation, microsurgery, and stereotactic radiosurgery (SRS) for small to medium‐sized vestibular schwannoma (VS) using a validated self‐assessment inventory; and (2) to identify clinical variables associated with long‐term dizziness handicap. Study Design Cross‐sectional observational study. Setting Two independent tertiary academic referral centers: one located in the United States and one in Norway. Subjects and Methods All patients with sporadic VS of less than 3 cm who underwent primary microsurgery, SRS, or observation between 1998 and 2008 were identified. Subjects were surveyed via a postal questionnaire using the Dizziness Handicap Inventory (DHI) and a VS symptom questionnaire. Results The overall survey response rate was 79%. A total of 538 respondents (mean age, 64 years; 56% female) were analyzed, and the mean time interval between treatment and survey was 7.7 years. Pretreatment variables associated with greater dizziness handicap included female sex, older age, larger tumor size, preexisting diagnosis of headache or migraine, and symptoms of dizziness predating treatment. Significant posttreatment features strongly associated with poor long‐term DHI scores included frequency and severity of ongoing headache. On multivariable analysis, treatment modality did not influence long‐term dizziness handicap. Conclusion At a mean of approximately 8 years following treatment, over half of patients with VS reported ongoing dizziness. The authors have identified several baseline features that may help predict the risk of lasting dizziness. Treatment modality does not appear to influence long‐term DHI score. We found a strong association between posttreatment headache and poor dizziness handicap. Future study is needed to further define this relationship.

Purpose We examined the utility of post-therapy surveillance imaging in a large, prospectively enrolled cohort of patients with diffuse large B-cell lymphoma (DLBCL) from the United States and confirmed our results in an independent cohort of patients from France. Methods Patients with newly diagnosed DLBCL and treated with anthracycline-based immunochemotherapy were identified from the Molecular Epidemiology Resource (MER) of the University of Iowa/Mayo Clinic Lymphoma Specialized Program of Research Excellence and the Léon Bérard Cancer Center, Lyon, France. In those with relapse, details at relapse and outcomes were abstracted from records. Results 680 individuals with DLBCL were identified from the MER, 552 (81%) of whom achieved remission after induction. 112 of the 552 patients (20%) suffered a relapse. The majority (64%) of relapses were identified before a scheduled follow-up visit. Surveillance imaging detected DLBCL relapse before clinical manifestations in nine out of 552 patients (1.6%) observed after therapy. In the Lyon cohort, imaging identified asymptomatic DLBCL relapse in four out of 222 patients (1.8%). There was no difference in survival after DLBCL relapse in patients detected at scheduled follow-up versus before scheduled follow-up in both the MER (P = .56) and Lyon cohorts (P = .25). Conclusion The majority of DLBCL relapses are detected outside of planned follow-up, with no difference in outcome in patients with DLBCL detected at a scheduled visit compared with patients with relapse detected outside of planned follow-up. These data do not support the use of routine surveillance imaging for follow-up of DLBCL.