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Immune System Diseases - Top 30 Publications

Rates and Trends of Pediatric Acute Lymphoblastic Leukemia - United States, 2001-2014.

Acute lymphoblastic leukemia (ALL) is the most prevalent cancer among children and adolescents in the United States, representing 20% of all cancers diagnosed in persons aged <20 years, or >3,000 new cases each year (1). Past studies reported increasing trends of ALL overall and among Hispanics, but these represented ≤28% of the U.S. population and did not provide state-based estimates (1-3). To describe U.S. ALL incidence rates and trends among persons aged <20 years during 2001-2014, CDC analyzed rigorous data (based on established publication criteria) from the United States Cancer Statistics data set, which includes incidence data on approximately 15,000 new cases per year of all types of invasive cancer among children and adolescents aged <20 years (4). The data set represented 98% of the U.S. population during the study period. Overall incidence of pediatric ALL during 2001-2014 was 34.0 cases per 1 million persons and among all racial/ethnic groups was highest among Hispanics (42.9 per 1 million). Both overall and among Hispanics, pediatric ALL incidence increased during 2001-2008 and remained stable during 2008-2014. ALL incidence was higher in the West than in any other U.S. Census region. State-specific data indicated that the highest rates of pediatric ALL incidence were in California, New Mexico, and Vermont. These demographic and geographic ALL incidence data might better inform public health interventions targeting the following areas: exposures to recognized risk factors for leukemia; ALL treatment, including clinical trial enrollment; survivorship care planning; and studies designed to understand the factors affecting changes in pediatric cancer incidence.

Lymphoproliferative responses to dendritic cell presentation of sensitizing allergens in atopic children with multiple allergies.

Peripheral blood mononuclear cells (PBMCs) proliferate inconsistently, rendering current lymphoproliferation assays unreliable in diagnosis.

Sensitization profiles to peanut allergens across the United States.

Measurement of IgE antibody to peanut components can aid in the prediction of allergic responses the food.

The national cost of asthma among school-aged children in the United States.

Recent research has quantified the national health care resource use (HCRU) and health care expenditure (HCE) burden associated with adult asthma; however, estimates specific to school-aged children are more than 2 decades old.

Allergic sensitization and objective measures of sleep in urban school-aged children with asthma.

Allergic sensitization is associated with increased child asthma morbidity and decreased pulmonary function. Nocturnal symptoms and/or awakenings typically are measured by self-report from diary data, whereas objective assessments of sleep in child asthma studies are lacking.

Single recombinant and purified major allergens and peptides: How they are made and how they change allergy diagnosis and treatment.

To review the current knowledge regarding recombinant and purified allergens and allergen-derived peptides.

Tenofovir alafenamide nephrotoxicity in an HIV-positive patient: A case report.

Tenofovir alafenamide (TAF) is novel prodrug of Tenofovir, a nucleotide reverse transcriptase inhibitor. TAF is less nephrotoxic than its predecessor prodrug, tenofovir disoproxil fumarate (TDF). Tenofovir causes mitochondrial dysfunction and tubular injury when there is elevated accumulation in proximal tubule cells. TAF's unique pharmacokinetic profile enables provision of lower required doses for antiviral efficacy. Lower concentrations reach renal tubules minimizing intracellular accumulation and mitochondrial damage. TAF has not been associated with the histologic markers of tenofovir-associated nephrotoxicity that are seen with TDF, such as dysmorphic mitochondria in proximal tubule cells. Here, we report a patient with dysmorphic mitochondria on kidney biopsy after initiating therapy with TAF.

Light therapy for multiple sclerosis-associated fatigue: Study protocol for a randomized controlled trial.

Fatigue is the most commonly reported symptom among multiple sclerosis (MS) patients, more than a quarter of whom consider fatigue to be their most disabling symptom. However, there are few effective treatment options for fatigue. We aim to investigate whether supplemental exposure to bright white light will reduce MS-associated fatigue.

Angioimmunoblastic T-cell lymphoma and hypereosinophilic syndrome with FIP1L1/PDGFRA fusion gene effectively treated with imatinib: A case report.

Hypereosinophilic syndrome (HES) is a rare disorder characterized by hypereosinophilia and organ damage. Some cases of HES are caused by the FIP1L1/PDGFRA fusion gene and respond to imatinib. FIP1L1/PDGFRA-positive HES occasionally evolves into chronic eosinophilic leukemia or into another form of myeloproliferative neoplasm; however, the development of a malignant lymphoma is very rare. We present a rare case of angioimmunoblastic T-cell lymphoma (AITL) and HES with the FIP1L1/PDGFRA gene rearrangement.

Multiparametric characterization of rare HIV-infected cells using an RNA-flow FISH technique.

Efforts to cure HIV are hampered by limited characterization of the cells supporting HIV replication in vivo and inadequate methods for quantifying the latent viral reservoir in individuals receiving antiretroviral therapy (ART). We describe a protocol for flow cytometric identification of viral reservoirs, based on concurrent detection of cellular HIV Gagpol mRNA by in situ RNA hybridization combined with antibody staining for the HIV Gag protein. By simultaneously detecting both HIV RNA and protein, the CD4 T cells harboring translation-competent virus can be identified. The HIV(RNA/Gag) method is 1,000-fold more sensitive than Gag protein staining alone, with a detection limit of 0.5-1 Gagpol mRNA(+)/Gag protein(+) cells per million CD4 T cells. Uniquely, the HIV(RNA/Gag) assay also allows parallel phenotyping of viral reservoirs, including reactivated latent reservoirs in clinical samples. The assay takes 2 d, and requires antibody labeling for surface and intracellular markers, followed by mRNA labeling and multiple signal amplification steps.

Connecting the Dots.

Moving Upstream - Anti-TSLP in Persistent Uncontrolled Asthma.

Severe and Difficult-to-Treat Asthma in Adults.

Editorial: Widening the Use of the Functional Lumen Imaging Probe to Kids With Eosinophilic Esophagitis: Esophageal Narrowing is not Just an Adult Problem.

The functional lumen imaging probe (FLIP) provides objective measurement of esophageal distensibility, thus offering a unique and potentially valuable assessment in eosinophilic esophagitis (EoE). Menard-Katcher and colleagues report the first study evaluating use of FLIP in pediatric patients that demonstrated a reduction in esophageal distensibility in patients with EoE compared to patients without EoE. An increase in esophageal distensibility was observed with age among pediatric patients without EoE, but not among those with EoE. While this study further supports the promise of esophageal distensibility assessment in EoE, future work remains needed to optimize FLIP utilization in both research and clinical settings.

Screen Time Engagement Is Increased in Urban Children With Asthma.

Physical activity in children has been shown to play a role in its relationship to asthma, both in terms of prevalence and incidence. One measure of physical activity in children is sedentary behavior, which might be measured by the degree of engagement with media electronic screens. We found that children with asthma, as compared with children without asthma, engage in significantly more hours of screen time (median 35 vs 26 h/wk, P = .004). In this birth cohort, those who developed a diagnosis of asthma at 8 years of age were significantly more engaged in electronic screen time than their peers. No other clinical or lifestyle behaviors were significantly associated with a diagnosis of asthma. Further study will be needed to determine directionality of this finding.

Comparing the Efficacy of DeVIC Therapy and High-dose Methotrexate Monotherapy with Whole-brain Radiation Therapy for Newly-diagnosed Primary Central Nervous System Lymphoma: A Single Institution Study.

In the current study, we aimed to compare DeVIC (dexamethasone, etoposide, ifosfamide and carboplatin) chemotherapy with high-dose methotrexate (HD-MTX) monotherapy plus whole-brain radiation therapy (WBRT) for newly-diagnosed primary central nervous system lymphoma (PCNSL), in terms of their efficacies and tolerability.

Will Chinese external therapy with compound Tripterygium wilfordii hook F gel safely control disease activity in patients with rheumatoid arthritis: design of a double-blinded randomized controlled trial.

Chinese external therapy (CET) is a topical application with mainly Chinese herb medicine therapy with thousands of years of historical implications and is a clinical routine that is commonly used for relieving joint-related symptoms in patients with arthritis in Chinese hospitals. However, there is a paucity of modern medical evidence to support its effectiveness and safety. Thus, we propose to implement a randomized, double-blinded, placebo-controlled clinical trial in patients with rheumatoid arthritis (RA) using, as the experimental intervention, topical application of a hospital-compounded gel preparation of Tripterygium wilfordii Hook F (TwHF).

Significance of Hyperferritinemia in Hospitalized Adults.

Although high ferritin levels are associated with iron overload, it is known that ferritin is also an acute-phase reactant that may be elevated in conditions associated with acute and chronic inflammation. In addition, an elevated ferritin level is a criterion for the diagnosis of hemophagocytic lymphohistiocytosis/macrophage activation syndrome (HLH/MAS). Therefore, the significance of elevated serum ferritin is often unclear. As HLH/MAS is a medical emergency, prompt diagnosis is important to guide appropriate treatment.

Therapeutic Mechanism of Glucocorticoids on Cellular Crescent Formation in Patients With Antiglomerular Basement Membrane Disease.

This study aimed to explore the therapeutic mechanism of glucocorticoids (GCs) in antiglomerular basement membrane disease.

Bortezomib-Induced Muscle Toxicity in Multiple Myeloma.

Multiple myeloma (MM) accounts for ∼13% of all hematologic malignancies. Bortezomib treatment is effective in MM, but can be complicated with neurological side effects. We describe a patient with symptomatic MM who had a reversible metabolic myopathy associated with bortezomib administration and pathologically characterized by excessive storage of lipid droplets together with mitochondrial abnormalities. In a single-center prospective study, 14 out of 24 patients with symptomatic MM were treated with bortezomib and, among these, 7 developed muscular signs and/or symptoms. The myopathy was characterized by a proximal muscle weakness involving lower limbs and was an early complication. Complete resolution of muscle weakness occurred after treatment discontinuation. Conversely, none of the patients who received a treatment without bortezomib developed muscular symptoms. Experimental studies demonstrate that in primary human myoblasts bortezomib at low concentrations leads to excessive storage of lipid droplets together with structural mitochondrial abnormalities, recapitulating the pathologic findings observed in patient's muscle. Our data suggest that patients treated with bortezomib should be monitored for muscular signs and/or symptoms and muscle weakness should alert the clinician to the possibility of myopathy. Bortezomib-induced metabolic myopathy is a potentially reversible entity with important implications for management and treatment of patients with MM.

Polarization-Sensitive Optical Coherence Tomographic Documentation of Choroidal Melanin Loss in Chronic Vogt-Koyanagi-Harada Disease.

Vogt-Koyanagi-Harada (VKH) disease is a systemic autoimmune disorder that affects organs with melanocytes. The sunset glow fundus (SGF) in VKH disease was evaluated with polarization-sensitive optical coherence tomography (PS-OCT).

Prevalence of Drug-Resistant Minority Variants in Untreated HIV-1-Infected Individuals With and Those Without Transmitted Drug Resistance Detected by Sanger Sequencing.

Minority variant human immunodeficiency virus type 1 (HIV-1) nonnucleoside reverse transcriptase inhibitor (NNRTI) resistance mutations are associated with an increased risk of virological failure during treatment with NNRTI-containing regimens. To determine whether individuals to whom variants with isolated NNRTI-associated drug resistance were transmitted are at increased risk of virological failure during treatment with a non-NNRTI-containing regimen, we identified minority variant resistance mutations in 33 individuals with isolated NNRTI-associated transmitted drug resistance and 49 matched controls. We found similar proportions of overall and nucleoside reverse transcriptase inhibitor-associated minority variant resistance mutations in both groups, suggesting that isolated NNRTI-associated transmitted drug resistance may not be a risk factor for virological failure during treatment with a non-NNRTI-containing regimen.

Evaluating the Impact of the Medical Education Partnership Initiative at the University of Zimbabwe College of Health Sciences Using the Most Significant Change Technique.

In medical education, evaluating outcomes from programs intended to transform attitudes or influence career trajectories using conventional methods of monitoring is often difficult. To address this problem, the authors adapted the most significant change (MSC) technique to gain a more comprehensive understanding of the impact of the Medical Education Partnership Initiative (MEPI) program at the University of Zimbabwe College of Health Sciences.

Model-based meta-analysis of progression-free survival in non-Hodgkin lymphoma patients.

Non-Hodgkin lymphoma (NHL) is a group of lymphoproliferative malignancies with varying treatment responses and progression-free survival (PFS) times. The objective of this study was to quantify the effect of treatment and patient-population characteristics on PFS in patients with NHL.

Classification and possible bacterial infection in outpatients with eczema and dermatitis in China: A cross-sectional and multicenter study.

Little is known about the classification and bacterial infection in outpatients with eczema and dermatitis in China.To investigate the prevalence of eczema and dermatitis in outpatients of dermatology clinics in China, examine classification and proportion of common types of dermatitis and the possible bacterial infection, and analyze the possible related factors.Outpatients with eczema or dermatitis from 39 tertiary hospitals of 15 provinces in mainland China from July 1 to September 30, 2014, were enrolled in this cross-sectional and multicenter study. Among 9393 enrolled outpatients, 636 patients (6.7%) were excluded because of incomplete information.The leading subtypes of dermatitis were unclassified eczema (35.5%), atopic dermatitis (13.4%), irritant dermatitis (9.2%), and widespread eczema (8.7%). Total bacterial infection rate was 52.3%, with widespread eczema, stasis dermatitis, and atopic dermatitis being the leading three (65.7%, 61.8%, and 61.4%, respectively). Clinically very likely bacterial infection has a significant positive correlation with disease duration, history of allergic disease, history of flexion dermatitis, and severe itching.Atopic dermatitis has become a common subtype of dermatitis in China. Secondary bacterial infection is common in all patients with dermatitis, and more attentions should be paid on this issue in other type of dermatitis apart from atopic dermatitis.

Fall prevalence in people with multiple sclerosis who use wheelchairs and scooters.

Falls are a serious health concern for persons with multiple sclerosis (PwMS) who use wheelchairs or scooters as their primary mode of mobility. Unfortunately, little is known about the fall prevalence and characteristics of this large segment of the multiple sclerosis (MS) community. The purpose of this study is to determine the prevalence and circumstances of falls in wheelchair and scooter users living with MS. Forty-four PwMS were recruited from research and medical centers in the United States and Asia. Participants completed a survey focusing on prevalence of falls, frequency of injurious falls, circumstances of the fall, and various quality of life indicators. A total of 44 individuals (32 females/11 males/1 not reported) aged 27 to 82 years (mean = 58 yrs) completed the survey. Seventy-five percent (n = 33) reported falling at least once in 6 months and 48% (n = 12) of those that fell sustained an injury. The majority (87.5%) of the falls occurred inside the home. Most individuals (76.7%; n = 33) reported concerns about falling and 65.9% (n = 29) limited their activities because of their concern of falling. Falls are prevalent in wheelchair and scooter users with MS. The observations highlight the need for interventions targeting this segment of the MS community.

The influence of inhaled corticosteroid discontinuation in children with well-controlled asthma.

Asthma is a chronic inflammatory disease that requires adherence to both preventative and therapeutic interventions in disease management. Children with asthma are likely to discontinue inhaled corticosteroids (ICS), especially when symptoms are under control. We aimed to investigate the impact of ICS adherence in children whose symptoms were under control.The study is cohort study; 35 children with controlled asthma that had undergone 3 years of follow-up were included. Serum eosinophil count, serum total IgE (tIgE), and lung function (FEV1, FEV1/FVC, PEF, FEF20-75%, and PC20) were evaluated at the beginning and end of the follow-up.At baseline, patients in both the adherent and nonadherent groups were similar. After 3 years, the nonadherent group who had discontinued ICS had a decrease in FEV1 (P < .05), FEV1/FVC (P < .05), PEF (P < .05), and FEF20-75% (P < .05). The nonadherent group had no significant improvement in PC20 compared with their values at the beginning of the follow-up, whereas the adherent group had improvement in PC20. Furthermore, there was an increase in serum eosinophil (P < .001) and tIgE (P < .05) in the nonadherent compared with the adherent group.Despite good asthma control, airway hyperresponsiveness (AHR) was detected in a large proportion of children with asthma. ICS discontinuation affected lung function, serum eosinophil count, tIgE, and AHR. Adequate adherence is important in asthma management. The benefits of ICS and the influence of drug discontinuation despite good asthma control may encourage better adherence from patients.

Are programmed cell death 1 gene polymorphisms correlated with susceptibility to rheumatoid arthritis?: A meta-analysis.

Several studies investigated the relationship between programmed cell death 1 (PDCD1) gene polymorphisms and rheumatoid arthritis (RA) risk, but the results were controversial. To explore whether PDCD1 gene polymorphisms have an effect on RA risk, we conducted this meta-analysis to investigate the relationships between PDCD1 polymorphisms (rs36084323 [PD-1.1 G/A], rs11568821 [PD-1.3 G/A] and rs2227981 [PD-1.5 C/T]) and RA risk under 4 genetic models.

Adherence, tolerability, and outcome after 36 months of isoniazid-preventive therapy in 2 rural clinics of Swaziland: A prospective observational feasibility study.

Although efficacy of 36 months isoniazid preventive therapy (IPT) among HIV-positive individuals has been proven in trial settings, outcome, tolerance, and adherence have rarely been evaluated in real-life settings.This is a prospective observational cohort study conducted in 2 primary care rural clinics in Swaziland.After negative tuberculosis symptom screening, patients either with the positive tuberculin skin test (TST) or after tuberculosis treatment were initiated on IPT for 144 weeks. In addition to routine clinic visits, adherence was assessed every semester.Of 288 eligible patients, 2 patients never started IPT (1 refusal, 1 contraindication), and 253 (87.8%), 234 (81.3%), and 228 (79.2%) were still on IPT after 48, 96, and 144 weeks, respectively (chiP = .01). Of 41 patients who interrupted IPT before 144 weeks, 21 defaulted (of which 17 also defaulted HIV care); 16 stopped because of adverse drug reactions; 2 were discontinued by clinicians' mistake and 1 because of TB symptoms. Five patients (1.7%) died of causes not related to IPT, 5 (1.7%) developed TB of which 2 were isoniazid-resistant, and 9 (3.1%) were transferred to another clinic. As an indicator of adherence, isoniazid could be detected in the urine during 86.3% (302/350) and 73.6% (248/337) of patient visits in the 2 clinics, respectively (chiP < .001).The routine implementation of IPT 36 months was feasible and good patient outcomes were achieved, with low TB incidence, good tolerance, and sustained adherence.

Association of croup with asthma in children: A cohort study.

Asthma and croup are common inflammatory airway diseases involving the bronchus in children. However, no study has reported the effects of urbanization, sex, age, and bronchiolitis on the association of croup and its duration with asthma development. We used the Taiwan Longitudinal Health Insurance Database (LHID) to perform this population-based cohort study; here, the cluster effect caused by hospitalization was considered to evaluate the association between croup and asthma development and the risk factors for asthma in children of different age groups. We evaluated children with croup aged <12 years (n = 1204) and age-matched control patients (n = 140,887) by using Cox proportional hazards regression analysis within a hospitalization cluster. Of all 142,091 patients, 5799 (including 155 with croup [419 per 1000 person-y] and 5644 controls [106 per 1000 person-y]) had asthma during the 5-year follow-up period. During the 5-year follow-up period, the hazard ratios (HRs [95% CIs]) for asthma were 2.10 (1.81-2.44) in all children with croup, 2.13 (1.85-2.46) in those aged 0 to 5 years, and 2.22 (1.87-2.65) in those aged 6 to 12 years. Children with croup aged 7 to 9 years had a higher HR for asthma than did those in other age groups. Boys with croup had a higher HR for asthma. The adjusted HR for asthma was 1.78 times higher in children with croup living in urban areas than in those living in rural areas. In conclusion, our analyses indicated that sex, age, bronchiolitis, and urbanization level are significantly associated with croup and asthma development. According to our cumulative hazard rate curves, younger children with croup should be closely monitored for asthma development for at least 3 years.