The Role of the IL23/IL17 Axis in Bronchiolitis Obliterans Syndrome After Lung Transplantation

Bronchiolitis obliterans syndrome (BOS) is the leading cause of death after lung transplantation. Treatment is challenging, as the precise pathophysiology remains unclear. We hypothesize that T_H17 lineage plays a key role in the pathophysiology of BOS by linking T‐cell activation to neutrophil influx and chronic inflammation. In a cross‐sectional study, bronchoalveolar lavage (BAL) samples of 132 lung transplant recipients were analyzed. Patients were divided in four groups: stable or suffering from infection (INF), acute rejection (AR) or BOS. The upstream T_H17 skewing (TGF‐β/IL1β/IL6/IL23), T_H17 counteracting (IL2), T_H17 effector cytokine (IL17) and the principal neutrophil‐attracting chemokine (IL8), were quantified at the mRNA or protein level in combination with the cell profiles. The BOS group (n = 36) showed an increase in IL1β protein (×1.5), IL6 protein (×3), transforming growth factor‐beta ( TGF‐β) mRNA (×3), IL17 mRNA (×20), IL23 mRNA (×10), IL8 protein (×2), IL8 mRNA (×3) and a decrease in IL2 protein (×0.8). The infection group (n = 11) demonstrated an increase in IL1β protein (×5), IL6 protein (×20), TGF‐β mRNA (×10), IL17 mRNA (×300), IL23 mRNA (×200) and IL8 protein (×6). The acute rejection group (n = 43) only revealed an increase in IL6 protein (×6) and IL8 protein (×2) and a decrease in IL2 protein (×0.7). Lymphocytes and neutrophils were increased in all groups compared to the stable (n = 42). Our findings demonstrate the IL23/IL17 axis to be involved in the pathophysiology of BOS potentially triggering the IL8‐mediated neutrophilia. IL6, IL1β and IL23 seem to be skewing cytokines and IL2 a counteracting cytokine for T_H17 alignment. The involvement of TGF‐β could not be confirmed, either as T_H17 steering or as counteracting cytokine.     

From visual performance to visual ergonomics: a personal historic view

During the author's active time in vision research a change in attitude took place from ‘visual performance’ as a criterion to justify higher light levels, to ‘visual ergonomics’ as a more comprehensive approach to improve visual work conditions. Some personal memories of this transition period may serve as a historic framework.     

Delay in the administration of all-trans retinoic acid and its effects on early mortality in acute promyelocytic leukemia: Final results of a multicentric study in the United States

Early death (ED) occurs in 10–30% of patients with acute promyelocytic leukemia (APL). Is all-trans retinoic acid (ATRA) promptly given and does it decrease overall early mortality? ATRA was administered within 24 h of morphological suspicion in only 44% of the 120 consecutive patients treated in the four collaborating centers. Absence of disseminated intravascular coagulation (p = 0.012) and admission to a non-university-affiliated hospital (p = 0.032) were independent predictors of ATRA delay. ED occurred in 17% of patients, and was independently correlated only with ICU admission (p = 0.002). Our results do not demonstrate that prompt (versus delayed) ATRA administration decreases overall early death.     

Manifestations of histoplasmosis

Two patients, a 34-year old man-to-woman transsexual and a 32-year-old man, with aids presented with pulmonary symptoms, fever, serious weight loss and an oral ulcer. A third patient, a 16-year-old boy, had signs of transverse myelitis and meningitis without immunodeficiency. All were South American citizens and had disseminated histoplasmosis. After antifungal treatment they recovered, although the third patient remained a wheelchair user. If pulmonary or miliary tuberculosis is suspected in a patient originating from South America, histoplasmosis should be considered. Oral ulcers and skin lesions can be diagnostic clues. Specific stainings of direct preparations and longer-lasting cultures of various materials, especially of biopsy samples, then provide the diagnosis.     

The burden of mental disorders: a comparison of methods between the Australian burden of disease studies and the Global Burden of Disease study

The national and Victorian burden of disease studies in Australia set out to examine critically the methods used in the Global Burden of Disease study to estimate the burden of mental disorders. The main differences include the use of a different set of disability weights allowing estimates in greater detail by level of severity, adjustments for comorbidity between mental disorders, a greater number of mental disorders measured, and modelling of substance use disorders, anxiety disorders and bipolar disorder as chronic conditions. Uniform age-weighting in the Australian studies produces considerably lower estimates of the burden due to mental disorders in comparison with age-weighted disability-adjusted life years. A lack of follow-up data on people with mental disorders who are identified in cross-sectional surveys poses the greatest challenge in determining the burden of mental disorders more accurately.