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.

     

Rewarming and cardiac surgery: a review

Patients undergoing cardiac surgery are mildly hypothermic by the completion of the surgical procedure. They need to return to a normothermic state if enzymatic functions are to proceed in their normal manner. The body can produce heat by elevating metabolic rate or by activating the shivering mechanism. Metabolic rate peaks shortly after separation of the patient from cardiopulmonary bypass, and therefore contributes to heat production. Because of the effects of neuromuscular blockage administered both during and after surgery; these patients may be unable to generate heat by shivering, and shivering is usually undesirable. This eliminates the major heat production mechanism available to the body. Therefore, heat must be transferred down its gradient by means of convection and conduction. External and internal methods accomplish these goals. External methods, which minimize additional heat loss, include the use of warming lights, elevation of room temperature, and the use of blankets. Internal methods, which transfer heat by convection, may be used to help actively reverse hypothermia. Such techniques include warmed inhalation gases and intravenous fluids, warmed nasogastric lavage fluid, and warmed peritoneal dialysis fluid for patients with end-stage renal failure with severe electrolyte disorders after surgery.     

Socioeconomic position and variations in coping strategies in musculoskeletal pain: a cross-sectional study of 1,287 40- and 50-year-old men and women.

OBJECTIVE: To examine the association between socioeconomic position and coping strategies in musculoskeletal pain. DESIGN AND SUBJECTS: Cross-sectional study of a random sample of 40- and 50-year-old Danes, participation rate 69%, n=7,125. The study included 1,287 persons who reported functional limitations due to musculoskeletal pain. METHODS: Data was collected by postal questionnaires and scales were developed on problem-solving coping and avoidant coping, based on a range of preliminary studies. Multivariate logistic regression analyses was used to study the correlation with socioeconomic position, measured by occupational social class. RESULTS: Among women, there was no correlation between social class and avoidant coping, but a significant decrease in the use of problem-solving coping by decreasing social class, adjusted odds ratio (OR) = 2.64 (95% confidence interval (CI) 1.31-5.32) in social class V vs social classes I + II. Among men, there was no correlation between social class and problem-solving coping, but a significant increase in the use of avoidant coping with decreasing social class, adjusted OR = 3.31 (95% CI 1.75-6.25) in V vs I + II. CONCLUSION: It is important for clinicians who advise and support patients in their response to musculoskeletal pain to be aware of socioeconomic differences in coping strategies. Gender differences in the association between socioeconomic factors and coping should be further investigated.     

An immunohistochemical investigation of diagnostic biopsy material taken from short and long term survivors with small cell lung cancer.

An immunohistochemical study has been carried out on fibre optic-biopsy specimens from patients with small cell lung cancer (SCLC) who had either died within 3 months, or who had survived more than 2 years. Long term survivors (LTS) were identified from completed clinical trials at major UK centres and were matched for age and sex within the trial with short term survivors (STS). The panel of immunohistochemical markers included those previously reported to be associated with prognosis, and reagents representative of both neuroendocrine and epithelial differentiation. A preliminary screen of 17 antibodies identified 11 as consistently reactive on paraffin-embedded material using streptavadin-biotin immunoperoxidase. Of 186 identified patients, 110 biopsy samples were retrieved. Of these, 70 gave sufficient material for analysis. All sections were scored by three observers without knowledge of the prognosis. The analysis failed to identify any antigen whose expression was correlated with prognosis. We conclude that, in fibre-optic biopsy specimens, immunohistochemical analysis does not add prognostic information in SCLC.     

Prospective evaluation of the effect on initial brain metastases from small cell lung cancer of platinum-etoposide based induction chemotherapy followed by an alternating multidrug regimen

BACKGROUND:: During the 1980s reports describing the effect of systemic chemotherapyon brain metastases from chemosensitive tumours emerged, includinga few retrospective reports on small cell lung cancer (SCLC)patients. DESIGN:: Previously untreated SCLC patients with no other malignancy,but in some cases with mixed histological subtype, who had symptomaticbrain metastases verified by contrast enhanced CT-scan, weretreated with a multidrug combination chemotherapy regimen andno cranial irradiation. Radiotherapy was optional at cranialrelapse or progression at the discretion of the physician incharge. The intracranial effect was evaluated by 4-weekly CT-scanand neurological examination, according to a standardized scoringsystem. END POINTS:: Intracranial response, duration of response, neurological score,terminal CNS status, and survival. RESULTS:: 21 patients were included, corresponding to 8.6% of consecutiveSCLC patients at our institution. 8 patients died before follow-upleaving 13 evaluable for response. In the former group, allpatients had WHO performance status of 3–4 compared to6/13 in the latter group. Of the 13 evaluable patients, 1 hadearly progression in the CNS and 1 had no change. 11 had CT-scanverified response, with a median duration of 135 days. Mostpatients, including all complete responders, had improvementin their neurological score. 6 out of 11 responders died withoutactive CNS disease. The crude median survival was 111 days,whereas the median survival(early deaths excluded) was 197 days. CONCLUSION:: Systemic combination chemotherapy was effective for palliationof initial brain involvement in the majority of patients ina small consecutive series. The role of consolidating cranialirradiation in responders should be assessed by a randomizedtrial. small cell carcinoma, brain metastases, chemotherapy     

Granulocyte-macrophage colony-stimulating factor enhances basophil histamine release induced by non-IgE-dependent stimulators

Some cytokines are known to affect IgE-mediated basophil histamine release. The effect of the cytokine granulocyte-macrophage colony-stimulating factor (GM-CSF) on human basophil and masct cell histamine release was studies further. Blood leukocytes with approximately 2% basophils from 9 healthy individuals were incubated with recombinant human GM-CSF (0.3–30 U/ml) in combination with A23187 (10^–7–10^–6 M) or washedStaphylococcus aureus whole bacteria (0.3–2.5 mg/ml). Histamine release was measured spectrofluorometrically. GM-CSF in itself did not induce histamine release. The addition of GM-CSF to cells stimulated with A 23187 caused a dose-dependent enhancement amounting to mean 70% at 3 U/ml and mean 170% at 30 U/ml (P<0.05). GM-CSF enhanced the bacteria-induced histamine release by 30% at U/ml and by 65% at 3 U/ml (P<0.05). The enhancement did not depend on cell-bound IgE or LPS contamination. In preliminary mast cell experiments with lung tissue we did not find an enancing effect of GM-CSF on IgE-mediated histamine release.