Secretion,blood levels and cutaneous expression of TL1A in psoriasis patients

TL1A is a TNF‐like cytokine which has been shown to co‐stimulate TH1 and TH17 responses during chronic inflammation. The expression of this novel cytokine has been investigated in inflammatory disorders like rheumatoid arthritis and inflammatory bowel disease, but little is known about expression and induction in psoriasis. Indeed, the pathogenesis in psoriasis is still not fully understood and it is speculated that cytokines other than TNF‐α are important in subsets of patients. Also, for patients with severe disease that are treated with systemic anti‐TNF‐α blockade, novel candidates to be used as disease and response biomarkers are of high interest. Here, we demonstrate TL1A expression in biopsies from psoriatic lesions. Also, we investigated spontaneous and induced TL1A secretion from PBMCs and blood levels from a cohort of psoriasis patients. Here, increased spontaneous secretion from PBMCs was observed as compared to healthy controls and a small subset of patients had highly elevated TL1A in the blood. Interestingly, activation of PBMCs with various cytokines showed a decreased sensitivity for TL1A activation in psoriasis patients compared to healthy controls.TL1A levels in blood and biopsies could not be correlated with disease activity with this patient cohort. Thus, additional large‐scale studies are warranted to investigate TL1A as a biomarker.     

Low-dose hydrocortisone in patients with COVID-19 and severe hypoxia (COVID STEROID) trial—Protocol and statistical analysis plan

Introduction

Severe acute respiratory syndrome coronavirus-2 has caused a pandemic of coronavirus disease (COVID-19) with many patients developing hypoxic respiratory failure. Corticosteroids reduce the time on mechanical ventilation, length of stay in the intensive care unit and potentially also mortality in similar patient populations. However, corticosteroids have undesirable effects, including longer time to viral clearance. Clinical equipoise on the use of corticosteroids for COVID-19 exists.

Methods

The COVID STEROID trial is an international, randomised, stratified, blinded clinical trial. We will allocate 1000 adult patients with COVID-19 receiving ≥10 L/min of oxygen or on mechanical ventilation to intravenous hydrocortisone 200 mg daily vs placebo (0.9% saline) for 7 days. The primary outcome is days alive without life support (ie mechanical ventilation, circulatory support, and renal replacement therapy) at day 28. Secondary outcomes are serious adverse reactions at day 14; days alive without life support at day 90; days alive and out of hospital at day 90; all-cause mortality at day 28, day 90, and 1 year; and health-related quality of life at 1 year. We will conduct the statistical analyses according to this protocol, including interim analyses for every 250 patients followed for 28 days. The primary outcome will be compared using the Kryger Jensen and Lange test in the intention to treat population and reported as differences in means and medians with 95% confidence intervals.

Discussion

The COVID STEROID trial will provide important evidence to guide the use of corticosteroids in COVID-19 and severe hypoxia.

     

Cognitive function after on or off pump coronary artery bypass grafting.

OBJECTIVE: To investigate cognitive outcome after on and off pump coronary artery bypass grafting. METHODS: Seventy patients between 50 and 80 years with stable angina pectoris, ejection fraction >30%, serum creatinine <150 micromol/l, and lack of tight main stem stenosis were randomized to on or off pump coronary artery bypass grafting. Standardized neuropsychological tests evaluated attention, verbal and visuo-spatial short-term and working memory, verbal learning, delayed recall, visuo-motor speed, and aspects of executive functions. Levels of anxiety and depression were also investigated. Testing was performed before and at 1 week, 1 and 6 months after surgery. RESULTS: There was no difference in cognitive impairment (defined as a 20% reduction in at least 20% of the tests) between groups. The incidence at 1 week post-operatively was 57% in the on pump group and 58% in the off pump group, after 1 month 30% and 12% and after 6 months 19% and 15%, respectively (p for interaction=0.19). There was no difference between groups in anxiety (p=0.18) or depression (p=0.48). CONCLUSIONS: This prospective, randomized study showed no differences in post-operative cognitive function after on pump compared to off pump coronary artery bypass grafting in low risk patients.     

Clinical safety of enamel matrix derivative (EMDOGAIN®) in the treatment of periodontal defects

Abstract The aim of the present clinical trial was to test tolerability during 2 treatments with EMDOGAIN® in a large number of patients. An open, controlled study design in 10 Swedish specialist clinics was chosen, with a test group of 107 patients treated with EMDOGAIN® in connection with periodontal surgery at 2 surgical test sites per patient. The procedures were performed 2 to 6 weeks apart on one-rooted teeth with at least 4 mm deep intraosseous lesions. A control group of 33 patients underwent flap surgery without EMDOGAIN® at I comparable site. In total 214 test and 33 control surgeries were performed. Serum samples were obtained from test patients for analysis of total and specific antibody levels. 10 of the patients had samples taken before and after the first surgery. 56 other samples were taken after one treatment with EMDOGAIN®, and 63 after 2 treatments. None of the samples, not even from allergy-prone patients after 2 treatments, indicated deviations from established baseline ranges. This indicates that the immunogenic potential of EMDOGAIN® is extremely low when applied in conjunction with periodontal surgery. Comparison between the test and control groups demonstrated the same type and frequency of post-surgical experiences, i.e., reactions caused by the surgical procedure itself. Clinical probing and radiographic evaluation was performed at baseline and 8 months postsurgery. About half of the patients (44 test and 21 control) were also evaluated after 3 years. There was a significant difference between the test and control results at 8 months post surgery. and this difference had increased further at the 3 year follow-up. The 2.5–3 mm increase in attachment and bone level after treatment with EMDOGAIN® was of the same magnitude as seen in the studies with split-mouth design aiming for lest of effectiveness of EMDOGAIN®.     

Cerebral function of the guinea pig neonate after chronic intrauterine exposure to khat (Catha edulis Forsk.)

Cerebral function in normoxia and its reactions to standard periods of hypoxia of increasing severity were studied in 30 newborn guinea pigs less than 3 days old. Intrauterine growth retardation was induced either by uterine artery ligation at midgestation or by feeding the female in late gestation with khat leaves, an amphetamine-like stimulant chewed by men and women in several countries in eastern Africa and Arabia. After spontaneous delivery, the neonates were anesthetized and ventilated. Cardiovascular, metabolic, and neurophysiologic (somatosensory evoked potentials) parameters were monitored. Under normoxia, the khat-exposed group showed prolonged latency of the primary response of the somatosensory evoked potentials and a reduced amount of secondary components. Under hypoxia, this group also has a greater reduction of amplitude of the somatosensory evoked potentials. It is concluded that khat exposure during fetal life has an impact on the cerebral function during the neonatal period (at least up to 3 days of age) which is not solely explained by the concomitantly produced growth retardation.     

Renal growth after neonatal urinary tract infection

This study presents the result of 12–21 years' follow-up in a group of children with neonatal urinary tract infection (onset within 1 month after birth) in whom early renal growth retardation was noted without concomitant classical renal scarring. In all cases the neonatal infection was diagnosed and treated within a few days of onset and the patients were closely supervised thereafter. Renal length, parenchymal thickness and area were measured at urography. At first follow-up (22 children, mean age 4.1 years) a significant reduction of renal parenchymal thickness was noted. Long-term follow-up (18 patients, mean age 17 years) demonstrated a normalization of renal size in the entire group, although less complete in the subgroup with reflux. There were two major findings in the present study. Firstly, renal growth retardation was seen after neonatal infection, both with and without reflux. Secondly, normalization of renal size in previously small kidneys was demonstrated, suggesting that growth retardation can be a reversible phenomenon. The tendency for such normalization was slightly more marked in children without reflux. Reduction of parenchymal thickness without calyceal deformity, therefore, does not necessarily mean irreversible damage, and differentiation between permanent scarring and temporary growth retardation can thus only be made at later follow-up, possibly not until after puberty. The demonstration of renal growth retardation in spite of early diagnosis and treatment emphasizes the great vulnerability of the kidney in the newborn.