Citations

Recent advances in follicular lymphoma (FL) have resulted in prolongation of overall survival (OS). Here we assessed if early events as defined by event‐free survival (EFS) at 12 and 24 months from diagnosis (EFS12/EFS24) can inform subsequent OS in FL. 920 newly diagnosed grade 1‐3A FL patients enrolled on the University of Iowa/Mayo Clinic Lymphoma SPORE Molecular Epidemiology Resource (MER) from 2002‐2012 were initially evaluated. EFS was defined as time from diagnosis to progression, relapse, re‐treatment, or death due to any cause. OS was compared to age‐and‐sex‐matched survival in the general US population using standardized mortality ratios (SMR) and 95% confidence intervals (CI). We used a cohort of 412 FL patients from two Lyon, France hospital registries for independent replication. Patients who failed to achieve EFS12 had poor subsequent OS (MER SMR = 3.72, 95%CI: 2.78‐4.88; Lyon SMR = 8.74, 95%CI: 5.41‐13.36). Conversely, patients achieving EFS12 had no added mortality beyond the background population (MER SMR = 0.73, 95%CI: 0.56‐0.94, Lyon SMR = 1.02, 95%CI: 0.58‐1.65). Patients with early events after immunochemotherapy had especially poor outcomes (EFS12 failure: MER SMR = 17.63, 95%CI:11.97‐25.02, Lyon SMR = 19.10, 95%CI:9.86‐33.36; EFS24 failure: MER SMR = 13.02, 95%CI:9.31‐17.74, Lyon SMR = 7.22, 95%CI:4.13‐11.74). In a combined dataset of all patients from both cohorts, baseline FLIPI was no longer informative in EFS12 achievers. Reassessment of patient status at 12 months from diagnosis in follicular lymphoma patients, or at 24 months in patients treated with immunochemotherapy, is a strong predictor of subsequent overall survival in FL. Early event status provides a simple, clinically relevant endpoint for studies assessing outcome in FL. Am. J. Hematol. 91:1096–1101, 2016. © 2016 Wiley Periodicals, Inc.

Polylactic acid (PLA) has a long history in medical applications. Reinforced PLA has the potential to be used in the medical applications that require high mechanical strength such as coronary stents and bone fixation devices. Halloysite nanotube (HNT) has received considerable attention recently due to its tubular structure, high aspect ratio, high mechanical strength, thermal stability, biocompatibility and sustained drug releasing properties. Halloysite has been investigated in compounding with many polymers. However, the research in compounding halloysite with biodegradable materials for use in biological applications is sparse. In this study various weight fractions of HNT was compounded with the biodegradable polymer PLA using a melt compounding method. Tensile test, Fourier infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), contact angle test, scanning electron microscopy (SEM), void content and thermogravimetric analysis (TGA) were carried out to study the PLA/HNT composite. Tensile test results indicated that Young's modulus and stiffness of PLA were enhanced with the addition of HNT; FTIR spectra showed the interaction between the PLA and HNT; whereas contact angle measurements indicated that the wettability of the PLA/HNT composite was not affected by the addition of HNT. However, the thermal stability of PLA was adversely effected by the addition of HNT which may be related to the presence of voids between the polymer and matrix. Nevertheless, the reinforced PLA/HNT composite, which maintains the surface characteristics, may prove beneficial for use in biological applications. POLYM. COMPOS., 38:2166–2173, 2017. © 2015 Society of Plastics Engineers

ObjectiveTo evaluate the incidence and prevalence of juvenile idiopathic arthritis (JIA) in Olmsted County, Minnesota in 1994–2013 and trends in juvenile rheumatoid arthritis (JRA) in 1960–2013.MethodsCases of arthritis in 1994–2013 were identified by diagnosis code with medical chart review to confirm diagnosis separately for JIA and JRA. Overall incidence rates with 95% confidence intervals (95% CIs) were age and sex adjusted to the 2010 US white population. Comparisons were made with an earlier (1960–1993) cohort from this same population.ResultsSeventy‐one incident cases of JIA in 1994–2013 were identified, with an overall age‐ and sex‐adjusted incidence rate of 10.3 per 100,000 (95% CI 7.9–12.7). Forty‐two (59%) were female, with an incidence of 12.4 per 100,000 (95% CI 8.6–16.2), as compared to 8.3 per 100,000 (95% CI 5.2–11.3) in males. The most common subtype was oligoarthritis (63%). The mean ± SD age at diagnosis was 8.2 ± 5.3 years. The prevalence of JIA on January 1, 2000 and January 1, 2010 was 51.0 per 100,000 (95% CI 25.2–76.8) and 57.6 per 100,000 (95% CI 31.0–94.5), respectively. When the annual incidence of JRA was compared over time from 1960 to 2013, there was no significant change in incidence overall; however, the incidence decreased among females (P = 0.003). A cyclic pattern of incidence was observed, with peaks approximately every 10 years. Similar to the findings with regard to incidence, prevalence did not change overall, but decreased among females (P = 0.048). There were 4 deaths in the cohort of JRA patients diagnosed in 1960–2013; the standardized mortality ratio was 1.50 (95% CI 0.41–3.83).ConclusionIncidence of juvenile arthritis overall in Olmsted County, Minnesota has not changed significantly in the past 53 years. A consistent cyclic pattern was noted.

1. Changes in afferent activity in the aortic and sinus nerves with alterations of blood pressure were studied in anaesthetized dogs. Mean aortic blood pressure was changed from 220 to 50 mmHg by using a pressurized reservoir connected to the abdominal aorta. 2. The stimulus-response curve (defined by measuring the mean impulse frequency at various pressures) from both nerves was S-shaped; the curve for the aortic nerve was shifted to the right of the sinus nerve curve. 3. In the dog, the aortic arch baroreceptors act predominantly as an anti-hypertensive mechanism; at lower pressures, the major control occurs through the sinus baroreflex.

ObjectiveTo determine trends in the incidence and clinical presentation of ankylosing spondylitis (AS), the incidence of cardiovascular disease (CVD), and cardiovascular (CV) risk factors among patients with AS and compare the observed incidence of CVD with that predicted by the Framingham Risk Score (FRS).MethodsA population‐based inception cohort of residents of Olmsted County, Minnesota age ≥18 years who fulfilled Modified New York Criteria for AS in 1980–2009 was assembled. Clinical features at presentation were recorded. Age‐ and sex‐adjusted incidence rates and survival were estimated. Incident CVD and CV risk factors were identified. The 10‐year CVD risk was calculated using the FRS. Standardized incidence ratios (ratios of observed CVD in AS to that predicted by the FRS) were calculated.ResultsEighty‐six patients were diagnosed with AS over the study period with an age‐ and sex‐adjusted incidence of 3.1 per 100,000 (95% confidence interval [95% CI] 2.5–3.8). The mean age at diagnosis was 35 years (range 19–69 years). Inflammatory back pain, seen in 90% of patients, was the most common presenting manifestation. The 10‐year mean ± SD cumulative incidence of CVD was 15.8% ± 6.1%, three times higher than the predicted events based on the FRS (standardized incidence ratio 3.01, 95% CI 1.35–6.69; P = 0.007). Overall survival was similar to the general population.ConclusionAS occurs in approximately 3 persons per 100,000 per year. Clinical features, extraarticular manifestations, and interval from symptom onset to diagnosis have remained constant in this population over the study period. The CVD risk in these patients is higher than expected and underestimated by the FRS.

Objective Epidemiologic studies comparing the incidence and prevalence of systemic lupus erythematosus (SLE) and isolated cutaneous lupus erythematosus (CLE) are few. Olmsted County, Minnesota provides a unique setting for such a study owing to resources of the Rochester Epidemiology Project. We sought to describe and compare the incidence and prevalence of SLE and CLE from 1993–2005. Methods SLE cases were identified from review of medical records and fulfilled the 1982 American College of Rheumatology classification criteria. CLE cases included patients with classic discoid lupus erythematosus, subacute CLE, lupus panniculitis, and bullous lupus erythematosus. Age‐ and sex‐adjusted incidence and prevalence were standardized to the 2000 US white population. Results The age‐ and sex‐adjusted incidence of SLE (2.9 per 100,000; 95% confidence interval [95% CI] 2.0–3.7) was similar to that of CLE (4.2 per 100,000; 95% CI 3.1–5.2, P = 0.10). However, the incidence of CLE was 3 times higher than SLE in men (2.4 versus 0.8 per 100,000; P = 0.009). The age‐ and sex‐adjusted prevalence of CLE on January 1, 2006 was higher than that of SLE (70.4 versus 30.5 per 100,000; P < 0.001). The prevalences of CLE and SLE in women were similar, but the prevalence of CLE was higher in men than in women (56.9 versus 1.6 per 100,000; P < 0.001). The incidence of CLE rose steadily with age and peaked at 60–69 years. Conclusion The incidences of CLE and SLE are similar, but CLE is more common than SLE in men and in older adults. These findings may reflect differences in genetic or environmental etiology of CLE.

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.

SummaryObjectiveTo evaluate safety, tolerability, seizure frequency, and regional variations in treatment responses with the AMPA antagonist, perampanel, in a large extension study during up to 3 years of treatment.MethodsPatients ≥12 years old with partial‐onset seizures despite treatment with 1–3 antiepileptic drugs at baseline completed a perampanel phase III trial and entered extension study 307 (NCT00735397). Patients were titrated to 12 mg/day (or their individual maximum tolerated dose) during the blinded conversion period, followed by open‐label maintenance. Exposure, safety (adverse events [AEs], vital signs, weight, electrocardiography [ECG], laboratory values) and seizure outcomes were analyzed; key measures were assessed by geographic regions.ResultsAmong 1,216 patients, median exposure was 1.5 years (range 1 week to 3.3 years), with >300 patients treated for >2 years. Treatment retention was 58.5% at cutoff. AEs reported in ≥10% of patients were dizziness, somnolence, headache, fatigue, irritability, and weight increase. Only dizziness and irritability caused discontinuation in >1% of patients (3.9% and 1.3%, respectively). The only serious AEs reported in >1% of patients were epilepsy‐related (convulsion, 3.0%; status epilepticus, 1.1%). No clinically relevant changes in vital signs, ECG or laboratory parameters were seen. After titration/conversion, responder rate and median percentage change from baseline in seizure frequency were stable: 46% for both measures at 9 months (in 980 patients with ≥9 months' exposure) and 58% and 60%, respectively, at 2 years (in the 337 patients with 2 years' exposure). Median percentage reduction in frequency of secondarily generalized (SG) seizures ranged from 77% at 9 months (N = 422) to 90% at 2 years (N = 141). Among the 694 patients with maintenance data ≥1 year, 5.3% were seizure‐free for the entire year.SignificanceNo new safety signals emerged during up to 3 years of perampanel exposure in 39 countries. Seizure responses remained stable, with marked reductions, particularly in SG seizures.A PowerPoint slide summarizing this article is available for download in the Supporting Information section here.