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.

     

Clinical versus ultrasonographic evaluation of scrotal disorders

Clinical and ultrasonographic examinations of scrotal disorders were compared in 166 patients in order to determine their ability to distinguish between those diseases requiring surgery and those requiring clinical follow-up only. Ultrasound examinations were efficient in discriminating between normal and pathological findings. Extra-testicular lesions were readily differentiated from testicular ones. Although both clinical and ultrasonographic examinations had high sensitivity (90%) in detecting testicular cancer, the number of false positive findings was smaller after ultrasound examination. This gave a predictive value of a positive test of 53% after ultrasound examination but only 33% after clinical examination. Ultrasound examination may, therefore, reduce the number of surgical explorations in the scrotum and should be performed in patients with suspected testicular pathology based on history and palpatory findings.     

Reevaluation of procarbazine for the treatment of recurrent malignant central nervous system tumors

Ninety-nine patients with primary recurrent malignant tumors of the central nervous system were treated with procarbazine as a single agent. Procarbazine was not given as a specified protocol, but for patients who were ineligible or refused other protocols. All patients had been treated previously with radiotherapy and 96 patients had also received previous chemotherapy. Twenty-five patients were treated at the first progression of their tumor, 47 were treated at the second progression, and 27 were treated at the third progression of their tumor. For the aggregate, the response plus stabilization rate was 27% for glioblastoma multiforme with median time to tumor progression of 30 weeks, and 28% for other anaplastic gliomas with a median time to tumor progression of 49 weeks. With respect to the percent of patients who responded or stabilized to treatment, these results are inferior to those reported previously for patients treated with procarbazine at recurrence. With respect to duration of response and stabilization, the data are comparable.     

Effect of anoxia on in vitro bladder function.

Previous studies have demonstrated that the ability of the in vitro whole bladder to empty in response to bethanechol administration was inhibited by anoxia while its ability to generate pressure decreased only slightly. One question was not addressed by these early studies: Is the anoxic effect selective for receptor-mediated contractile stimulation (as opposed to non-receptor-mediated contractile stimulation)? The present study was designed to compare the effect of anoxia on the ability of the in vitro bladder to generate pressure, sustain pressure, and empty in response to field stimulation (FS), bethanechol and KC1 administration. Each New Zealand white rabbit was anesthetized with pentobarbital and the bladder removed. The bladder was mounted as a whole-bladder preparation in a 300-ml isolated bath containing Tyrode's solution at 37 degrees C and equilibrated with 95% O2, 5% CO2. Anoxia was produced by changing the gas mixture to 95% nitrogen, 5% CO2. The effect of anoxia on the response to FS, bethanechol, and KCl was determined at different times after the initiation of anoxia. The results of these studies can be summarized as follows. (1) Anoxia induced a time-dependent decrease in the rate of pressure generation, the magnitude of pressure generation, and the percent volume emptied in response to FS and bethanechol. (2) At all time periods of anoxia, the ability of the bladder to empty was inhibited to a significantly greater degree than either the rate of magnitude of pressure generation (for both FS and bethanechol administration).(ABSTRACT TRUNCATED AT 250 WORDS)     

The effect of atrial natriuretic peptide on human isolated resistance arteries.

1. The action of (1-28) alpha-human atrial natriuretic peptide (ANP) was studied on human isolated resistance arteries. 2. Renal, skeletal muscle, omental and subcutaneous resistance arteries were taken from tissue removed at surgery and isometric tension responses were measured with a myograph. 3. ANP (10(-9)-10(-6) M) relaxed precontracted segments of renal and skeletal muscle arteries in a concentration-dependent manner. ANP failed to relax isolated omental or subcutaneous arteries. 4. The effect of ANP on human isolated resistance arteries varies depending on the site of origin of the artery.     

Resident and staff perceptions of barriers to independence and employment in supportive living settings for persons with AIDS.

The purpose of this study was to identify perceived barriers to independent community living and employment among clients and staff members in a transitional living facility for persons with AIDS. This qualitative study used focus groups to collect these perceptions from staff members (N = 21) and clients (N = 16). Whereas staff identified both systemic and personal barriers, clients only identified systemic barriers. These findings suggest that both clients and staff recognize the types of environmental barriers to participation that have been identified by disability scholars. The findings also underscore a consequential gap between clients' exclusive emphasis on environmental barriers and staff emphasis on clients' personal barriers that impact upon participation.