Modern management of chronic granulomatous disease

Chronic granulomatous disease (CGD) is a rare primary immunodeficiency disorder of phagocytic cells resulting in failure to kill a characteristic spectrum of bacteria and fungi and in defective degradation of inflammatory mediators with concomitant granuloma formation. Current prophylaxis with trimethoprim-sulfamethoxazole, itraconazole and in selected cases additional interferon gamma is efficient, but imperfect. A significant recent progress towards new antibiotic (e.g. linezolid) and antifungal (e.g. voriconazole and posaconazole) therapy will allow survival of most patients into adulthood. Adolescent and adult CGD is increasingly characterized by inflammatory complications, such as granulomatous lung and inflammatory bowel disease, requiring immunosupressive therapy. Allogeneic haematopoietic stem cell transplantation from a human leucocyte antigen identical donor is currently the only proven curative treatment for CGD and can be offered to the selected patients. Gene-replacement therapy for patients lacking a suitable stem cell donor is still experimental and faces major obstacles and risks. However, it may offer some transitory benefits and has helped in a few cases to overcome life-threatening infections

Is plasma renin activity associated with worse outcomes in acute heart failure? A secondary analysis from the BLAST-AHF trial

Aims: Neurohormonal activation characterizes chronic heart failure (HF) and is a well-established therapeutic target. Neurohormonal activation may also play a key role in acute HF (AHF). We aim to describe the association between plasma renin activity (PRA) and three AHF outcomes: (i) worsening HF or death through day 5 of hospitalization; (ii) HF rehospitalization or death through day 30; and (iii) all-cause death through day 30. Methods and results: A secondary analysis of the BLAST-AHF trial was performed. Eligible patients had a history of HF, elevated natriuretic peptides, signs and symptoms of HF, systolic blood pressure >120 mmHg, and an estimated glomerular filtration rate between 20–75 mL/min/1.73 m2. The primary trial was neutral, with no differential effect of study drug by PRA levels. Baseline PRA levels were grouped into tertiles. Adjusted Cox proportional hazard model determined the association of PRA levels with outcomes (α set at P < 0.05). Of 618 randomized patients, 578 (93.5%) had a baseline PRA. PRA was modestly, but significantly, associated with each outcome without adjustment [worsening HF or death through day 5: hazard ratio (HR) 1.11, 95% confidence interval (CI) 1.01–1.23, P = 0.04; HF rehospitalization or death through day 30: HR 1.13, 95% CI 1.02–1.26, P = 0.02; all-cause death through day 30: HR 1.18, 95% CI 1.02–1.37, P = 0.03]. After multivariable adjustment, PRA was only significantly associated with HF rehospitalization or death through day 30 (HR 1.15, 95% CI 1.01–1.32, P = 0.04). Conclusion: Baseline PRA levels are associated with increased risk for the composite of 30-day HF rehospitalization or death in patients with AHF. © 2019 The Authors. European Journal of Heart Failure © 2019 European Society of Cardiolog

Immunohistochemical investigation of the tissue distribution of mannan-binding lectin in non-infected and virus-infected chickens.

This paper describes the results of immuno-histochemical staining for chicken mannan-binding lectin (MBL) in formalin-fixed tissue sections from non-infected chickens, and from chickens infected with infectious laryngotracheitis virus (ILTV) or infectious bursal disease virus (IBDV). In the non-infected chickens, MBL was detected in the cytoplasm of a few hepatocytes and in the germinal centres of the caecal tonsils, whereas sections of kidney, heart muscle, spleen, cerebrum, thymus, adrenal gland, bursa of Fabricius, bone marrow and trachea were without staining. In the ILTV-infected chickens, an intense staining reaction for MBL was detected in the cytoplasm of all hepatocytes and on the surface of, and inside, ILTV-infected cells. Also in the IBDV-infected chickens, an intense staining reaction for MBL was detected in the cytoplasm of all hepatocytes. No staining was seen in the follicles of the bursa of Fabricius, but MBL was present in non-identified cells in the interstitium, and in the cytoplasm of macrophage-like cells, located peripheral to the ellipsoid of the spleen. These findings indicate the liver as the primary site of MBL synthesis, and points to up-regulation as a result of the viral infections. The location outside the liver could indicate a role of MBL in the immune defence