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Immune System Diseases - Top 30 Publications

Trial of Tocilizumab in Giant-Cell Arteritis.

Trial of Tocilizumab in Giant-Cell Arteritis.

Trial of Tocilizumab in Giant-Cell Arteritis.

Trial of Tocilizumab in Giant-Cell Arteritis.

Self-Reported Decline in Everyday Function, Cognitive Symptoms, and Cognitive Function in People With HIV.

We determined factors associated with self-reported decline in activities of daily living (ADLs) and symptoms of cognitive impairment in HIV positive adults in 5 European clinics.

Brief Report: HIV/HBV Coinfection is a Significant Risk Factor for Liver Fibrosis in Tanzanian HIV-Infected Adults.

In sub-Saharan Africa, the burden of liver disease associated with chronic hepatitis B virus (HBV) and HIV is unknown. We characterized liver disease using aspartate aminotransferase-to-platelet ratio index (APRI) and FIB-4 in patients with HIV, HBV, and HIV/HBV coinfection in Tanzania.

How entry inhibitors synergize to fight HIV.

HIV fusion with the cell membrane can be inhibited by blocking coreceptor binding or by preventing fusion-inducing conformational changes in the Env protein. Logically, inhibitors that act by these two mechanisms should act synergistically, but previous studies have reported conflicting results. A new study by Ahn and Root reconciles these discordant reports by demonstrating that synergy emerges when Env engages multiple coreceptors prior to inducing fusion and when high-affinity inhibitory peptides are used, a condition that may not be satisfied in vivo.

Anti-Ma2-associated limbic encephalitis with coexisting chronic inflammatory demyelinating polyneuropathy in a patient with non-Hodgkin lymphoma: A case report.

We report the rare case of a 74-year-old man with anti-Ma2-associated paraneoplastic neurologic syndrome (PNS), and review and analyze the clinical manifestations, diagnosis, and treatment of the disease.

Implementation effectiveness of revised (post-2010) World Health Organization guidelines on prevention of mother-to-child transmission of HIV using routinely collected data in sub-Saharan Africa: A systematic literature review.

To synthesize and evaluate the impact of implementing post-2010 World Health Organization (WHO) prevention of mother-to-child transmission (PMTCT) guidelines on attainment of PMTCT targets.

Phase 1 study of the anti-CD22 immunotoxin moxetumomab pasudotox for childhood acute lymphoblastic leukemia.

Novel therapies are needed to overcome chemotherapy resistance for children with relapsed/refractory acute lymphoblastic leukemia (ALL). Moxetumomab pasudotox is a recombinant anti-CD22 immunotoxin. A multicenter phase 1 study was conducted to determine the maximum-tolerated cumulative dose (MTCD) and evaluate safety, activity, pharmacokinetics, and immunogenicity of moxetumomab pasudotox in children, adolescents, and young adults with ALL (N = 55). Moxetumomab pasudotox was administered as a 30-minute IV infusion at doses of 5 to 50 µg/kg every other day for 6 (cohorts A and B) or 10 (cohort C) doses in 21-day cycles. Cohorts B and C received dexamethasone prophylaxis against capillary leak syndrome (CLS). The most common treatment-related adverse events were reversible weight gain, hepatic transaminase elevation, and hypoalbuminemia. Dose-limiting CLS occurred in 2 of 4 patients receiving 30 µg/kg of moxetumomab pasudotox every other day for 6 doses. Incorporation of dexamethasone prevented further dose-limiting CLS. Six of 14 patients receiving 50 µg/kg of moxetumomab pasudotox for 10 doses developed hemolytic uremic syndrome (HUS), thrombotic microangiopathy (TMA), or HUS-like events, exceeding the MTCD. Treatment expansion at 40 µg/kg for 10 doses (n = 11) exceeded the MTCD because of 2 HUS/TMA/HUS-like events. Dose level 6B (ie, 50 µg/kg × 6 doses) was the MTCD, selected as the recommended phase 2 dose. Among 47 evaluable patients, an objective response rate of 32% was observed, including 11 (23%) composite complete responses, 5 of which were minimal residual disease negative by flow cytometry. Moxetumomab pasudotox showed a manageable safety profile and evidence of activity in relapsed or refractory childhood ALL. This trial was registered at as #NCT00659425.

Febuxostat as a Prophylaxis for Tumor Lysis Syndrome in Children with Hematological Malignancies.

The aim of the present study was to determine if febuxostat could prevent tumor lysis syndrome (TLS) in children who received induction chemotherapy for hematologic malignancies.

The Significance of PET/CT in the Initial Staging of Hodgkin Lymphoma: Experience Outside Clinical Trials.

To examine the real-life impact of baseline positron-emission tomography/computed tomography (PET/CT) in Hodgkin lymphoma (HL).

Programmed Cell Death Ligand 1 Expression in Primary Central Nervous System Lymphomas: A Clinicopathological Study.

Programmed cell death ligand 1 (PD-L1)/programmed cell death 1 (PD-1) have been shown to predict response to PD-L1/PD-1-targeted therapy. We analyzed PD-L1 expression in primary central nervous system lymphomas (PCNSLs).

Modulation of PI3K/PTEN Pathway Does Not Affect Catalytic Activity of PDK1 in Jurkat Cells.

Unopposed phosphoinositide 3-kinase (PI3K) activity and 3-phosphoinositide production in Jurkat cells, due to a mutation in the phosphatase and tensin homolog deleted on chromosome 10 (PTEN) tumor-suppressor protein, results in deregulation of PH domain-containing proteins including the serine/threonine kinase PKB. In Jurkat cells, PKB is constitutively active and phosphorylated at the activation-loop residue (Thr308). 3-Phosphoinositide-dependent protein kinase-1 (PDK1), an enzyme that also contains a PH domain, catalyses Thr308 phosphorylation of PKB in addition to other kinase families such as PKC isoforms. It is unknown, however, whether the loss of PTEN in Jurkat cells also results in unregulated PDK1 activity and whether such loss has an impact on activation-loop phosphorylation of other PDK1 substrates e.g. PKC. In this study, we addressed whether loss of PTEN in Jurkat cells affects PDK1 catalytic activity and intracellular localization. We demonstrated that reducing the level of 3-phosphoinositides in Jurkat cells with pharmacological inhibitors of PI3K or expression of PTEN does not affect PDK1 activity or its intracellular localization. We conclude, therefore, that although Jurkat cells lack PTEN expression, only a subset of pathways downstream of PDK1 are perturbed as a consequence of PTEN loss.

Retention in Medical Care Among Insured Children with Diagnosed HIV Infection - United States, 2010-2014.

In 2014, an estimated 2,477 children aged <13 years were living with diagnosed human immunodeficiency virus (HIV) infection in the United States (1). Nationally, little is known about how well children with a diagnosis of HIV infection are retained in medical care. CDC analyzed insurance claims data to evaluate retention in medical care for children in the United States with a diagnosis of HIV infection. Data sources were the 2010-2014 MarketScan Multi-State Medicaid and MarketScan Commercial Claims and Encounters databases. Children aged <13 years with a diagnosis of HIV infection in 2010 were identified using International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) diagnostic billing codes for HIV or acquired immunodeficiency syndrome (AIDS), resulting in Medicaid and commercial claims cohorts of 163 and 129 children, respectively. Data for each child were evaluated during a 36-month study period, counted from the date of the first claim containing an ICD-9-CM code for HIV or AIDS. Each child's consistency of medical care was assessed by evaluating the frequency of medical visits during the first 24 months of the study period to see if the frequency of visits met the definition of retention in care. Frequency of medical visits was then assessed during an additional 12-month follow-up period to evaluate differences in medical care consistency between children who were retained or not retained in care during the initial 24-month period. During months 0-24, 60% of the Medicaid cohort and 69% of the commercial claims cohort were retained in care, among whom 93% (Medicaid) and 85% (commercial claims) were in care during months 25-36. To identify areas for additional public health action, further evaluation of the objectives for national medical care for children with diagnosed HIV infection is indicated.

Anti-TCRβ mAb in Combination With Neurogenin3 Gene Therapy Reverses Established Overt Type 1 Diabetes in Female NOD Mice.

Insulin-producing β cells in patients with type 1 diabetes (T1D) are destroyed by T lymphocytes. We investigated whether targeting the T-cell receptor (TCR) with a monoclonal antibody (mAb) abrogates T-cell response against residual and newly formed islets in overtly diabetic nonobese diabetic (NOD) mice. NOD mice with blood glucose levels of 250 to 350 mg/dL or 350 to 450 mg/dL were considered as new-onset or established overt diabetes, respectively. These diabetic NOD mice were transiently treated with an anti-TCR β chain (TCRβ) mAb, H57-597, for 5 days. Two weeks later, some NOD mice with established overt diabetes further received hepatic gene therapy using the islet-lineage determining gene Neurogenin3 (Ngn3), in combination with the islet growth factor gene betacellulin (Btc). We found that anti-TCRβ mAb (50 µg/d) reversed >80% new-onset diabetes in NOD mice for >14 weeks by reducing the number of effector T cells in the pancreas. However, anti-TCRβ mAb therapy alone reversed only ∼20% established overt diabetes in these mice. Among those overtly diabetic NOD mice whose diabetes was resistant to anti-TCRβ mAb treatment, ∼60% no longer had diabetes when they also received Ngn3-Btc hepatic gene transfer 2 weeks after initial anti-TCRβ mAb treatment. This combination of Ngn3-Btc gene therapy and anti-TCRβ mAb treatment induced the sustained formation of periportal insulin-producing cells in the liver of overtly diabetic mice. Therefore, directly targeting TCRβ with a mAb potently reverses new-onset T1D in NOD mice and protects residual and newly formed gene therapy-induced hepatic neo-islets from T-cell‒mediated destruction in mice with established overt diabetes.

Which Anti-CD20 Antibody Is Better in Follicular Lymphoma?

Hematologic Malignancies Discovered on Investigation of Breast Abnormalities.

Hematological malignancies of the breast share a presentation similar to primary breast carcinomas but differ substantially in therapeutic approach and clinical outcomes. In this study, we investigate the frequency of hematological malignancies, their relative primary and secondary occurrences, and further characterize the distinct histopathologies of these malignancies with a special focus on lymphomas. To our knowledge this is one of the largest and most comprehensive studies of breast hematologic malignancies.

Prehematopoietic Stem Cell Transplantation Tear Cytokines as Potential Susceptibility Biomarkers for Ocular Chronic Graft-Versus-Host Disease.

To determine if cytokine tear levels before hematopoietic stem cell transplantation (HSCT) can help anticipate the occurrence of ocular chronic graft-versus-host disease (cGVHD).

HIV status and hearing loss among children between 6 and 12 years of age at a large urban health facility in south western Uganda.

Pediatric HIV infection and treatment may increase the risk for hearing loss (HL), both sensorineural (SNHL) and conductive hearing loss (CHL). There is limited data on this subject, especially from sub Saharan Africa. The aim of this study was therefore to compare the prevalence of hearing loss among HIV positive and negative children, to determine the types of hearing loss and whether Nevirapine (NVP) based antiretroviral therapy (ART) is associated with HL.

Idiopathic CD4 lymphocytopenia: Pathogenesis, etiologies, clinical presentations and treatment strategies.

Idiopathic CD4 lymphocytopenia (ICL) is a rare condition characterized by an unexplained deficit of circulating CD4 T cells leading to increased risk of serious opportunistic infections. The pathogenesis, etiology, clinical presentation, and best treatment options remain unclear.

Risk factors for severe anaphylaxis in the United States.

Anaphylaxis is an acute systemic allergic reaction and may be life-threatening.

Contemporary issues in anaphylaxis and the evolution of epinephrine autoinjectors: What will the future bring?

Food allergy and anaphylaxis appear to be increasing in the United States, especially in young children, and preparedness is paramount to successful emergency management in the community. Although the treatment of choice for anaphylaxis is epinephrine delivered by autoinjection, some devices are challenged by less user-friendly designs or pose the risk of injury, especially in young patients. Human factors engineering has played a larger role in the development of more recent epinephrine autoinjector technologies and will continue to play a role in the evolution and future design of epinephrine autoinjectors.

Comparing biosimilar SB2 with reference infliximab after 54 weeks of a double-blind trial: clinical, structural and safety results.

SB2 is a biosimilar to the reference infliximab (INF). Similar efficacy, safety and immunogenicity between SB2 and INF up to 30 weeks were previously reported. This report investigates such clinical similarity up to 54 weeks, including structural joint damage.

Clinical characteristics of inflammatory ocular disease in anti-neutrophil cytoplasmic antibody associated vasculitis: a retrospective cohort study.

To characterize the clinical correlates and outcome of inflammatory ocular disease (IOD) among patients with ANCA-associated vasculitides (AAV).

Risk factors of serious infections in patients with rheumatoid arthritis treated with tocilizumab in the French Registry REGATE.

Observational studies have already reported the risk of serious infections in RA treated with tocilizumab, but in limited samples. The aim of this study was to investigate the predictive risk factors for serious infections in the largest European registry of patients treated with tocilizumab for RA.

Rheumatoid arthritis patients with continued low disease activity have similar outcomes over 10 years, regardless of initial therapy.

To compare 10-year disease outcomes of RA patients who have continuous low disease activity and are on MTX with or without initial combination therapy with infliximab or prednisone and SSZ.

Disease activity dynamics in rheumatoid arthritis: patients' self-assessment of disease activity via WebApp.

The aim was to evaluate patient self-assessment of RA disease activity in terms of Routine Assessment of Patient Index Data (RAPID) scores via a Web-based smartphone application (WebApp).

Enrichment of malondialdehyde-acetaldehyde antibody in the rheumatoid arthritis joint.

To characterize the expression of malondialdehdye-acetaldehyde (MAA) adducts and anti-MAA antibody in articular tissues and serum of patients with RA.

Using a reference when defining an abnormal MRI reduces false-positive MRI results-a longitudinal study in two cohorts at risk for rheumatoid arthritis.

The use of hand and foot MRI in the diagnostic process of RA has been advocated. Recent studies showed that MRI is helpful in predicting progression from clinically suspect arthralgia (CSA) to clinical arthritis, and from undifferentiated arthritis (UA) to RA. Symptom-free persons can also show inflammation on MRI. This study aimed to evaluate if MRI findings in symptom-free volunteers are relevant when defining a positive MRI.