Low immunoglobulin levels increase the risk of severe hypogammaglobulinemia in granulomatosis with polyangiitis patients receiving rituximab

License: Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/)Background: Randomized controlled trials and retrospective studies in ANCA-associated vasculitis (AAV) concurred that rituximab (RTX) is effective to induce and maintain remission. Infections and hypogammaglobulinemia during RTX were usually infrequent and uncomplicated. But in the Tromsø study cohort, 45 % of patients with granulomatosis with polyangiitis (GPA) developed hypogammaglobulinemia during RTX maintenance leading to its discontinuation in 62 %. Methods: To explain these differences in outcome when using RTX in AAV to maintain remission, we used statistical structural methods to compare the Tromsø study cohort with other published cohorts. Results: GPA patients’ characteristics of the Tromsø study cohort were not so different compared with other cohorts. Rates of hypogammaglobulinemia and discontinuation of RTX seemed closely related to the cut-off used and to the levels of immunoglobulin (Ig) at baseline. Combination of low IgG serum levels at baseline (7.7 g/L) and low cut-off to define hypogammaglobulinemia in the Tromsø study cohort explained the high rate of hypogammaglobulinemia and discontinuation of RTX. Conclusions: Patients’ characteristics in the Tromsø study cohort were not skewed, apart from IgG levels. Low IgG level at baseline seemed to contribute the most to hypogammaglobulinemia and its complication

CRP as a marker for myocardial infarction and for damage accrual in systemic lupus erythematosus patients: results from a single-centre longitudinal study

CRP is a marker of inflammation and is also a known cardiovascular risk factor. Patients with systemic lupus erythematosus (SLE) have moderately elevated CRP levels and develop organ damage , that includes an increased rate of cardiovascular events

Risk Factors and Adverse Events Poorly Predict Infections and Hypogammaglobulinemia in Granulomatosis with Polyangiitis Patients Receiving Rituximab

Background. 29 GPA patients from the Northern Norway vasculitis disease registry received rituximab (RTX) induction and maintenance. 24% and 31% had, respectively, severe and chronic infections while 45% had hypogammaglobulinemia and 28% discontinued RTX due to hypogammaglobulinemia. The aim of the study was to examine how known predictors and adverse events interacted with adverse events using structural statistical methods. Methods. Five predictors (age, cyclophosphamide, total Ig and CD4/CD8 ratio prior RTX, and type of RTX maintenance regimen) and 4 adverse events (severe and chronic infections, hypogammaglobulinemia, and RTX discontinuation) were modeled in principal component and redundancy analyses. Results. The 5 predictors explained 51% of the variance of the GPA cohort. Models including cyclophosphamide exposure and total Ig level predicted best adverse events. However total Ig level has low R squared. The 2 best combinations of adverse events explained 13% of the variance of the predictors and adverse events. Only chronic infections were associated with combination of all adverse events (P=0.014). Hypogammaglobulinemia did not seem associated with the other adverse events. Conclusions. Traditional risk factors for infections and hypogammaglobulinemia seemed to poorly predict adverse events in our GPA cohort

GP-confirmed complete Achilles tendon rupture using pocket-sized ultrasound: a case report

Source at https://doi.org/10.3399/bjgpopen17X100893. The incidence of complete Achilles tendon rupture is 18 per 100 000 patient-years and is usually diagnosed clinically by GPs. The extent of clinical misdiagnosis is unknown in Norway, but may be high. This is important as delayed treatment has unfavourable consequences. We report how a GP, with no clinical ultrasound experience, recorded images with a pocket-sized ultrasound device (PSUD) under supervision to confirm a complete Achilles tendon rupture. This could present a new indication for GP ultrasound

El cultivo del caqui

En este libro se escribe del caqui en toda su amplitud, los mejores investigadores en las diferentes especialidades nos explican los resultados de la investigación y experiencias en fertirrigación, pies y variedades, sanidad vegetal, poda y postcosecha; acompañado y documentado de una amplia bibliografía de los investigadores de los principales países productores del mundo: China, Japón e Israel, e Italia, más que por su producción, por su continua y avanzada investigación. Este libro, fruto del trabajo de las diferentes líneas de investigación del producto, coordinada por el magnífico equipo de investigadores del IVIA, pone a disposición de la producción, postcosecha y comercialización todos los avances conocidos a nivel nacional e internacional

Omecamtiv mecarbil in chronic heart failure with reduced ejection fraction, GALACTIC‐HF: baseline characteristics and comparison with contemporary clinical trials

Aims: The safety and efficacy of the novel selective cardiac myosin activator, omecamtiv mecarbil, in patients with heart failure with reduced ejection fraction (HFrEF) is tested in the Global Approach to Lowering Adverse Cardiac outcomes Through Improving Contractility in Heart Failure (GALACTIC‐HF) trial. Here we describe the baseline characteristics of participants in GALACTIC‐HF and how these compare with other contemporary trials. Methods and Results: Adults with established HFrEF, New York Heart Association functional class (NYHA) ≥ II, EF ≤35%, elevated natriuretic peptides and either current hospitalization for HF or history of hospitalization/ emergency department visit for HF within a year were randomized to either placebo or omecamtiv mecarbil (pharmacokinetic‐guided dosing: 25, 37.5 or 50 mg bid). 8256 patients [male (79%), non‐white (22%), mean age 65 years] were enrolled with a mean EF 27%, ischemic etiology in 54%, NYHA II 53% and III/IV 47%, and median NT‐proBNP 1971 pg/mL. HF therapies at baseline were among the most effectively employed in contemporary HF trials. GALACTIC‐HF randomized patients representative of recent HF registries and trials with substantial numbers of patients also having characteristics understudied in previous trials including more from North America (n = 1386), enrolled as inpatients (n = 2084), systolic blood pressure < 100 mmHg (n = 1127), estimated glomerular filtration rate < 30 mL/min/1.73 m2 (n = 528), and treated with sacubitril‐valsartan at baseline (n = 1594). Conclusions: GALACTIC‐HF enrolled a well‐treated, high‐risk population from both inpatient and outpatient settings, which will provide a definitive evaluation of the efficacy and safety of this novel therapy, as well as informing its potential future implementation

Potential patient benefit of a subcutaneous formulation of tocilizumab for the treatment of rheumatoid arthritis: a critical review.

Treatment of rheumatoid arthritis (RA) was revolutionized during the last decade with the development of new biologic disease-modifying anti-rheumatic drugs (DMARDs) enabling the targeting of immune cells and cytokines other than tumor necrosis factor (TNF). Subcutaneous formulations of the newer biologic DMARDs facilitate not only patients’ emancipation from the hospital, but reduce both societal and medical costs. Intravenous tocilizumab (TCZ) in RA has an efficacy and safety profile similar to anti-TNF in both the short and long-term. However, TCZ can be administered in monotherapy without loss of efficacy when patients do not tolerate methotrexate or synthetic DMARDs. TCZ is consistently found superior to methotrexate and possibly superior to adalimumab in monotherapy in randomized controlled trials. Subcutaneous administration of TCZ is as effective and safe as its intravenous administration in RA patients during the first year of treatment. Similar to intravenous TCZ, patients’ weight and possibly previous use of anti-TNF influence the efficacy of subcutaneous TCZ. Additionally, combination with synthetic DMARDs seems to expose RA patients to more adverse events independently of its administration route. Pharmacokinetics of different administration routes could potentially lead to differences in efficacy, adverse events, and auto-immunogenicity. The concentration of free TCZ before new TCZ dose (C trough) is higher in the subcutaneous route, while the maximal concentration of free TCZ is higher in the intravenous route. The subcutaneous dosages of TCZ 162 mg every week, and every 2 weeks in RA patients with low body weight (60 kg) work well. Nevertheless, dosage and intervals of subcutaneous TCZ administration could be adjusted during the course of treatment since 80% of non-Japanese RA patients with usually higher body weight achieved similar efficacy with the low TCZ dosage in combination with a synthetic DMARD. Patients want effective, easy-to-administer therapy with sustained prolonged efficacy without the need of polypharmacy and with minimal to no side effects. Subcutaneous TCZ in RA patients in monotherapy seems to live up to patients’ expectations