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Immune System Diseases - Top 30 Publications

Ocrelizumab in Primary Progressive and Relapsing Multiple Sclerosis.

Ocrelizumab in Primary Progressive and Relapsing Multiple Sclerosis.

Ocrelizumab in Primary Progressive and Relapsing Multiple Sclerosis.

Ocrelizumab in Primary Progressive and Relapsing Multiple Sclerosis.

Ocrelizumab in Primary Progressive and Relapsing Multiple Sclerosis.

Ocrelizumab in Primary Progressive and Relapsing Multiple Sclerosis.

Comorbidities of rheumatoid arthritis: Results from the Korean National Health and Nutrition Examination Survey.

This study aimed to evaluate the prevalence of comorbidities in patients with rheumatoid arthritis (RA) compared with the non-RA population. The 2010-2012 Korea National Health and Nutrition Examination Survey (KNHANES), which assesses the general health status of populations in South Korea using interviews and basic health assessment, was analyzed retrospectively. Weighted prevalence and odds ratio (OR) of comorbidities were analyzed in patients with RA compared with the non-RA population. The overall weighted (n = 37,453,158) prevalence of RA was 1.5%. Patients with RA were older and more female predominant than subjects without RA. The prevalence of living in an urban area, college graduation, alcohol consumption and smoking was lower in patients with RA than non-RA. Patients with RA had more comorbidities including hypertension, dyslipidemia, myocardial infarction (MI) or angina, stoke, osteoarthritis, lung cancer, colon cancer, pulmonary tuberculosis, asthma, diabetes, depression, thyroid disease and chronic kidney disease. After adjusting socioeconomic and lifestyle characteristics, RA was associated with an increased prevalence of MI or angina (OR 1.86, 95% CI 1.17-2.96, p = 0.009), pulmonary TB (OR 1.95, 95% CI 1.24-3.09, p = 0.004), asthma (OR 1.97, 95% CI 1.05-3.71, p = 0.036), thyroid disease (OR 1.71, 95% CI 1.05-2.77), depression (OR 2.38, 95% CI 1.47-3.85, p < 0.001) and hepatitis B (OR 2.34, 95% CI 1.15-4.80, p = 0.020) compared with the non-RA population. Prevalence of solid cancer was not significantly associated with RA after adjustment.

The lack of BTK does not impair monocytes and polymorphonuclear cells functions in X-linked agammaglobulinemia under treatment with intravenous immunoglobulin replacement.

The lack of BTK in X-linked agammaglobulinemia (XLA) patients does not affect monocytes and polymorphonuclear cells (PMN) phenotype and functions. In this study, we show that XLA patients had an increased frequency of the intermediate monocytes subset and that BTK-deficient monocytes and PMN had a normal expression of receptors involved in the activation and cellular responses. We demonstrate that BTK is not required for migration, phagocytosis and the production of reactive oxygen species (ROS) following engagement of FC gamma receptors (FcγR). XLA monocytes and PMN showed an efficient calcium (Ca2+)-independent activation of oxidative burst, suggesting that oxidative burst is less dependent by Ca2+ mobilization. The phagocytosis was functional and it remained unaltered also after Ca2+ chelation, confirming the independence of phagocytosis on Ca2+ mobilization. Intravenous immunoglobulin (IVIg) infusion exerted an anti-inflammatory effect by reducing the frequency of pro-inflammatory monocytes. In monocytes, the IVIg reduce the oxidative burst and phagocytosis even if these functions remained efficient.

Females with Unexplained Joint Pain Following Total Joint Arthroplasty Exhibit a Higher Rate and Severity of Hypersensitivity to Implant Metals Compared with Males: Implications of Sex-Based Bioreactivity Differences.

Recent studies indicate that females demonstrate an increased risk of experiencing adverse local tissue reactions, aseptic loosening, and revision after primary metal-on-metal hip resurfacing arthroplasty compared with males; the underlying biological mechanisms responsible for sex discrepancies in implant failure remain unclear. In addition to anatomical and biomechanical sex differences, there may be inherent immunological disparities that predispose females to more aggressive adaptive immune reactivity to implant debris, i.e., metal sensitivity.

Range of Risk Factor Levels: Control, Mortality, and Cardiovascular Outcomes in Type 1 Diabetes Mellitus.

Individuals with type 1 diabetes mellitus (T1DM) have a high risk of cardiovascular complications, but it is unknown to what extent fulfilling all cardiovascular treatment goals is associated with residual risk of mortality and cardiovascular outcomes in those with T1DM compared with the general population.

Serum C-reactive protein concentrations in Nova Scotia Duck Tolling Retrievers with immune-mediated rheumatic disease.

Nova Scotia Duck Tolling Retrievers (NSDTRs) are a dog breed often affected by immune-mediated rheumatic disease (IMRD), a disorder characterised by chronic stiffness and joint pain. Most, but not all, dogs with IMRD, have antinuclear antibodies (ANA), which are also commonly present in the autoimmune disease systemic lupus erythematosus (SLE). The clinical and diagnostic findings of IMRD indicate that it is an SLE-related disorder. C-reactive protein (CRP), an acute phase protein, is a quantitative marker of inflammation for many diseases and is used for diagnosing and monitoring systemic inflammation in both humans and dogs. However, in human SLE, CRP concentrations are often elevated but correlate poorly with disease activity; they can be low in individual patients with active disease. The aim of the study was to investigate CRP in a group of NSDTRs with the SLE-related disorder IMRD. The hypothesis was that CRP concentrations would be increased in dogs with IMRD compared to healthy dogs, but that the increase would be mild. Serum CRP concentrations were measured in 18 IMRD-affected NSDTRs and 19 healthy control NSDTRs using two different canine-specific CRP assays. Dogs with IMRD and ANA had higher CRP concentrations than the control dogs, but the concentrations were below the clinical decision limit for systemic inflammation for most of the IMRD dogs. These results indicate that CRP concentrations were increased in dogs with IMRD and ANA, but the increase was mild, similar to what has been observed in human SLE.

The treatment of primary mediastinal large B-cell lymphoma: a two decades monocentric experience with 98 patients.

The purpose of this study is to investigate the most suitable first-line approach and the best combination treatment for primary mediastinal large B-cell lymphoma (PMLBCL) as they have been matter of debate for at least two decades.

Lower Physical Activity in Persons with Multiple Sclerosis at Increased Fall Risk: A Cross-sectional Study.

Persons with multiple sclerosis (MS) often report being afraid of falling, and this may have effects on physical activity (PA) engagement. This study investigated PA levels in persons with MS as a function of fall risk categories. Forty-seven persons with MS participated in the study and were categorized into either increased fall risk (IFR; n = 21; 55.5 ± 9.0 years) or normal fall risk (NFR; n = 26; 51.2 ± 12.9 years) groups based on scores from the Activities-Balance Confidence scale. PA was measured by accelerometer and expressed as average steps per day, and time spent in sedentary behavior, light PA, and moderate to vigorous physical activity over the course of 7 consecutive days. Univariate and covariate analyses were used to compare the differences in PA between fall risk groups. The average steps per day of the NFR group was significant higher compared with the IFR group (6024 ± 2533.1 vs. 2599 ± 1622.7 steps; P < 0.001), and the difference remained after controlling for disability level (5351 ± 2298.6 vs. 3432 ± 2363.6 steps; P = 0.016). There were no differences in light PA and moderate to vigorous physical activity between groups after controlling for disability level. Persons with MS at IFR accumulate fewer steps per day compared with those at NFR. This underscores the need for well-designed interventions targeting walking in this population who are far from the recommended 10,000 steps, particularly those with IFR.

Fourier transform power spectrum is a potential measure of tissue alignment in standard MRI: A multiple sclerosis study.

Loss of tissue coherency in brain white matter is found in many neurological diseases such as multiple sclerosis (MS). While several approaches have been proposed to evaluate white matter coherency including fractional anisotropy and fiber tracking in diffusion-weighted imaging, few are available for standard magnetic resonance imaging (MRI). Here we present an image post-processing method for this purpose based on Fourier transform (FT) power spectrum. T2-weighted images were collected from 19 patients (10 relapsing-remitting and 9 secondary progressive MS) and 19 age- and gender-matched controls. Image processing steps included: computation, normalization, and thresholding of FT power spectrum; determination of tissue alignment profile and dominant alignment direction; and calculation of alignment complexity using a new measure named angular entropy. To test the validity of this method, we used a highly organized brain white matter structure, corpus callosum. Six regions of interest were examined from the left, central and right aspects of both genu and splenium. We found that the dominant orientation of each ROI derived from our method was significantly correlated with the predicted directions based on anatomy. There was greater angular entropy in patients than controls, and a trend to be greater in secondary progressive MS patients. These findings suggest that it is possible to detect tissue alignment and anisotropy using traditional MRI, which are routinely acquired in clinical practice. Analysis of FT power spectrum may become a new approach for advancing the evaluation and management of patients with MS and similar disorders. Further confirmation is warranted.

Acceptability and feasibility of early infant male circumcision for HIV prevention in Malawi.

Voluntary medical male circumcision (VMMC) has been successfully implemented in 14 countries as an additional HIV prevention intervention. As VMMC programs mature in most countries, the focus is now on how to sustain the HIV prevention gains realised from VMMC. As part of preparations for the sustainability phase, countries are either piloting or preparing to pilot early infant male circumcision (EIMC). This qualitative study explored the acceptability and feasibility of EIMC in Malawi in order to inform pilot implementation.

Voice disorder in systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is a chronic disease characterized by progressive tissue damage. In recent decades, novel treatments have greatly extended the life span of SLE patients. This creates a high demand for identifying the overarching symptoms associated with SLE and developing therapies that improve their life quality under chronic care. We hypothesized that SLE patients would present dysphonic symptoms. Given that voice disorders can reduce life quality, identifying a potential SLE-related dysphonia could be relevant for the appraisal and management of this disease. We measured objective vocal parameters and perceived vocal quality with the GRBAS (Grade, Roughness, Breathiness, Asthenia, Strain) scale in SLE patients and compared them to matched healthy controls. SLE patients also filled a questionnaire reporting perceived vocal deficits. SLE patients had significantly lower vocal intensity and harmonics to noise ratio, as well as increased jitter and shimmer. All subjective parameters of the GRBAS scale were significantly abnormal in SLE patients. Additionally, the vast majority of SLE patients (29/36) reported at least one perceived vocal deficit, with the most prevalent deficits being vocal fatigue (19/36) and hoarseness (17/36). Self-reported voice deficits were highly correlated with altered GRBAS scores. Additionally, tissue damage scores in different organ systems correlated with dysphonic symptoms, suggesting that some features of SLE-related dysphonia are due to tissue damage. Our results show that a large fraction of SLE patients suffers from perceivable dysphonia and may benefit from voice therapy in order to improve quality of life.

Sensitive quantification of the HIV-1 reservoir in gut-associated lymphoid tissue.

The implementation of successful strategies to achieve an HIV cure has become a priority in HIV research. However, the current location and size of HIV reservoirs is still unknown since there are limited tools to evaluate HIV latency in viral sanctuaries such as gut-associated lymphoid tissue (GALT). As reported in the so called "Boston Patients", despite undetectable levels of proviral HIV-1 DNA in blood and GALT, viral rebound happens in just few months after ART interruption. This fact might imply that current methods are not sensitive enough to detect residual reservoirs. Showing that, it is imperative to improve the detection and quantification of HIV-1 reservoir in tissue samples. Herein, we propose a novel non-enzymatic protocol for purification of Lamina Propria Leukocytes (LPL) from gut biopsies combined to viral HIV DNA (vDNA) quantification by droplet digital PCR (ddPCR) to improve the sensitivity and accuracy of viral reservoir measurements (LPL-vDNA assay).

Dividing CKD stage 3 into G3a and G3b could better predict the prognosis of IgA nephropathy.

Chronic kidney disease (CKD) stage 3 was divided into stage G3a and stage G3b in the 2013 Kidney Disease Improving Global Outcomes guidelines. Whether it is appropriate to regard 45 mL/min/per 1.73 m2 as the threshold value of G3a/G3b staging and whether dividing CKD stage 3 into G3a/G3b plays a useful role in assessing the prognosis of patients with IgA nephropathy (IgAN) remain unknown. Three hundred and ninety patients from the First Affiliated Hospital of Zhengzhou University and Peking University First Hospital diagnosed with IgAN in CKD stage 3 were enrolled and successfully followed up. Cox proportional hazards model was used to analyze hazard ratios of reaching the composite endpoints (doubling of serum creatinine, end-stage renal disease: estimated glomerular filtration rate (eGFR) <15 ml/min/per 1.73 m2 or renal replacement therapy, or death) for patients with different eGFR and risk factors affecting composite endpoints. The Kaplan-Meier method was used to calculate the cumulative renal survival rate of patients. When eGFR was lower than 45 ml/min/per 1.73 m2, the hazard ratio increased sharply for patients in CKD stage 3 who reached the composite endpoints. Renal injury and prognosis were significantly different between patients in the G3a and G3b groups. Stage G3b was a major risk factor affecting prognosis. A threshold value of 45 ml/min/per 1.73 m2 appears appropriate to assess the prognosis of IgAN patients with CKD stage 3. Dividing IgAN patients with CKD stage 3 into G3a and G3b is very useful to help understand disease conditions and for predicting the risk for disease progression.

Barriers and facilitators for men to attend prenatal care and obtain HIV voluntary counseling and testing in Brazil.

Providing HIV voluntary counseling and testing (VCT) to men who attend their partner's prenatal care is an intervention with potential to reduce HIV transmission to women and infants during the vulnerable period of pregnancy. Little is known about the acceptability of this intervention in global settings outside of Africa.

Absence of antibodies against KIR4.1 in multiple sclerosis: A three-technique approach and systematic review.

Antibodies targeting the inward-rectifying potassium channel KIR4.1 have been associated with multiple sclerosis (MS) but studies using diverse techniques have failed to replicate this association. The detection of these antibodies is challenging; KIR4.1 glycosylation patterns and the use of diverse technical approaches may account for the disparity of results. We aimed to replicate the association using three different approaches to overcome the technical limitations of a single technique. We also performed a systematic review to examine the association of anti-KIR4.1 antibodies with MS.

"Support Your Client at the Space That They're in": HIV Pre-Exposure Prophylaxis (PrEP) Prescribers' Perspectives on PrEP-Related Risk Compensation.

Despite the demonstrated effectiveness of HIV pre-exposure prophylaxis (PrEP) and evidence that most PrEP users do not engage in risk compensation (i.e., increased risk behavior due to a perceived decrease in HIV susceptibility), some healthcare providers report patient risk compensation to be a deterrent to prescribing PrEP. Overcoming this barrier is essential to supporting PrEP access and uptake among people at risk for HIV. To inform such efforts, this qualitative study explored PrEP-related risk compensation attitudes among providers with firsthand experience prescribing PrEP. US-based PrEP providers (n = 18), most of whom were HIV specialists, were recruited through direct outreach and referral from colleagues and other participants. Individual 90-min semistructured interviews were conducted by phone or in person from September 2014 through February 2015, transcribed, and thematically analyzed. Three attitudinal themes emerged: (1) providers' role is to support patients in making informed decisions, (2) risk behavior while taking PrEP does not fully offset PrEP's protective benefit (i.e., PrEP confers net protection, even with added behavioral risk), and (3) PrEP-related risk compensation is unduly stigmatized within and beyond the healthcare community. Participants were critical of other healthcare providers' negative judgment of patients and reluctance to prescribe PrEP due to anticipated risk compensation. Several providers also acknowledged an evolution in their thinking from initial ambivalence toward greater acceptance of PrEP and PrEP-related behavior change. PrEP providers' insights about risk compensation may help to address unsubstantiated concerns about PrEP-related risk compensation and challenge the acceptability of withholding PrEP on these grounds.

Catastrophic outcome of patients with a rebound after Natalizumab treatment discontinuation.

Natalizumab (NTZ) is an effective drug for the treatment of relapsing-remitting multiple sclerosis. In some patients discontinuation is mandatory due to the risk of progressive multifocal leukoencephalopathy. However, severe clinical and radiological worsening has been described after drug cessation. Our aim was to describe the clinical and radiological features of the rebound phenomenon.

Variation within MBP gene predicts disease course in multiple sclerosis.

Prognosis following a first demyelinating event is difficult to predict, with no genetic markers of MS progression currently identified. Myelin basic protein (MBP) is a major component of the myelin sheath of CNS neurons and may play a central role in demyelinating diseases such as MS. However, genetic variation in MBP has not been implicated in MS onset risk in large genome-wide association studies. We hypothesized that genetic variations in MBP may be a determinant of MS clinical course.

Diversity in mental fatigue and social profile of patients with myasthenia gravis in two different Northern European countries.

Self-estimated health can be used for comparison of different diseases between countries. It is important to elaborate on whether disparities in self-estimated health are due to disease-specific parameters or socioeconomic differences. In this study, we aimed at evaluating clinical and social similarities and differences in myasthenia gravis (MG) patients between comparable regions in two Baltic Sea countries, Estonia and Sweden.

Elevated C-X-C motif ligand 13 and B-cell-activating factor levels in neuromyelitis optica during remission.

Discovery of specific antibodies against astrocytic water channel aquaporin-4 (AQP4), which is produced by plasma cells, in the serum of neuromyelitis optica (NMO) confirmed the pathogenic role of B cells in NMO. C-X-C motif ligand 13 (CXCL13) and B-cell-activating factor (BAFF) are two crucial factors for antibody production. Relevant studies have focused on the acute phase of NMO. However, CXCL13 and BAFF levels during remission, remain to be elucidated.

Overview of cancer incidence and mortality among people living with HIV/AIDS in British Columbia, Canada: Implications for HAART use and NADM development.

The objective of this study is to evaluate the incidence of non-AIDS defining malignancies (NADMs) among people living with HIV/AIDS (PLWHA) in British Columbia, focusing on clinical correlates, highly active antiretroviral therapy (HAART) use, and survival, in order to elucidate mechanisms for NADM development.

Diabetes mellitus in patients with chronic obstructive pulmonary disease-The impact on mortality.

Chronic obstructive pulmonary disease (COPD) is the leading cause of morbidity and mortality worldwide. There is evidence to support a connection between COPD and diabetes mellitus (DM), another common medical disorder. However, additional research is required to improve our knowledge of these relationships and their possible implications. In this study, we investigated the impact of DM on patient outcomes through the clinical course of COPD.

Plasma from patients with anti-glomerular basement membrane disease could recognize microbial peptides.

Infection has long been suspected as a trigger of autoimmune diseases, and molecular mimicry mechanism was hypothesized in this study. Microbe originated peptides were searched from the Uniprot database based on a previous defined critical amino acid motif within α3129-150, isoleucine137, tryptophan140, glycine142, phenylalanine 143 and phenylalanine 145. 23826 microbial peptides were identified using our searching strategy, among which seven were related with human infections. Circulating IgG and IgM antibodies against the seven microbial peptides were detected using ELISA in 76 patients with anti-GBM disease. Four peptides were recognized by both IgG and IgM antibodies, and one peptide was recognized by IgG antibodies only. Peptides from Bacteroides, Saccharomyces cerevisiae, and Bifidobacterium thermophilum possessed the highest recognition frequency with the prevalence of 73.7%, 61.8% and 67.1% for IgG, 56.6%, 44.7% and 67.1% for IgM in anti-GBM patients. Patients with antibodies against these microbial peptides showed more severe kidney injury, including higher serum creatinine and higher percentage of crescent formation. In conclusion, antibodies against microbial peptides were identified in the circulation of anti-GBM patients, implying its etiological role in eliciting autoimmune response against α3(IV)NC1 through molecular mimicry.

Factors influencing postnatal Option B+ participation and breastfeeding duration among HIV-positive women in Lilongwe District, Malawi: A qualitative study.

To ensure the health of mothers and children, prevention of mother-to-child HIV transmission (PMTCT) programs test women for HIV, engage HIV-positive women in care, and promote recommended breastfeeding practices. Under Malawi's Option B+ PMTCT program, ~20% of women are lost-to-follow-up (LTFU) and little is known about their breastfeeding practices. The purpose of this study is to describe facilitators and barriers to Option B+ participation and how participation influences breastfeeding duration. We conducted in-depth interviews with HIV-positive women in Option B+ (n = 32) or LTFU from Option B+ (n = 32). They were recruited from four government clinics in Lilongwe District and had a child aged 0-23 months. Women in Option B+ had better disclosure experiences and more social support than LTFU women. The most common reasons for LTFU were fear of HIV disclosure, anticipated or experienced stigma, and insufficient social support. Other reasons included: non-acceptance of HIV status, antiretroviral therapy (ART) side effects, lack of funds for transport, and negative experiences with clinic staff. Worries about possible transmission, even while on ART, influenced timing of weaning for some women in Option B+. Despite their knowledge of the risk of HIV transmission to the child, most LTFU women continued to breastfeed after stopping ART because they considered breastmilk to be an important source of nutrients for the child. Given that HIV-positive Malawian women LTFU from Option B+ breastfeed in the absence of ART, efforts are needed to use evidence-based strategies to address the barriers to Option B+ participation and avert preventable transmission through breastmilk.

Cost-Effectiveness of TNF-Blocker Injection Spacing for Patients with Established Rheumatoid Arthritis in Remission: An Economic Evaluation from the Spacing of TNF-Blocker Injections in Rheumatoid Arthritis Trial.

In patients with rheumatoid arthritis in remission, a disease activity-driven tapering of adalimumab or etanercept relying on progressive injection spacing has not been shown to be equivalent to a maintenance strategy at full dose in terms of disease activity in the Spacing of TNF-blocker injections in Rheumatoid ArthritiS Study (STRASS) trial.