Author Correction: Enhanced NF-κB signaling in type-2 dendritic cells at baseline predicts non-response to adalimumab in psoriasis.

Funder: Department of HealthBiologic therapies have transformed the management of psoriasis, but clinical outcome is variable leaving an unmet clinical need for predictive biomarkers of response. Here we perform in-depth immunomonitoring of blood immune cells of 67 patients with psoriasis, before and during therapy with the anti-TNF drug adalimumab, to identify immune mediators of clinical response and evaluate their predictive value. Enhanced NF-κBp65 phosphorylation, induced by TNF and LPS in type-2 dendritic cells (DC) before therapy, significantly correlates with lack of clinical response after 12 weeks of treatment. The heightened NF-κB activation is linked to increased DC maturation in vitro and frequency of IL-17+ T cells in the blood of non-responders before therapy. Moreover, lesional skin of non-responders contains higher numbers of dermal DC expressing the maturation marker CD83 and producing IL-23, and increased numbers of IL-17+ T cells. Finally, we identify and clinically validate LPS-induced NF-κBp65 phosphorylation before therapy as a predictive biomarker of non-response to adalimumab, with 100% sensitivity and 90.1% specificity in an independent cohort. Our study uncovers important molecular and cellular mediators underpinning adalimumab mechanisms of action in psoriasis and we propose a blood biomarker for predicting clinical outcome

Hemicraniectomy after middle cerebral artery infarction with life-threatening Edema trial (HAMLET). Protocol for a randomised controlled trial of decompressive surgery in space-occupying hemispheric infarction

<p>Abstract</p> <p>Background</p> <p>Patients with a hemispheric infarct and massive space-occupying brain oedema have a poor prognosis. Despite maximal conservative treatment, the case fatality rate may be as high as 80%, and most survivors are left severely disabled. Non-randomised studies suggest that decompressive surgery reduces mortality substantially and improves functional outcome of survivors. This study is designed to compare the efficacy of decompressive surgery to improve functional outcome with that of conservative treatment in patients with space-occupying supratentorial infarction</p> <p>Methods</p> <p>The study design is that of a multi-centre, randomised clinical trial, which will include 112 patients aged between 18 and 60 years with a large hemispheric infarct with space-occupying oedema that leads to a decrease in consciousness. Patients will be randomised to receive either decompressive surgery in combination with medical treatment or best medical treatment alone. Randomisation will be stratified for the intended mode of conservative treatment (intensive care or stroke unit care). The primary outcome measure will be functional outcome, as determined by the score on the modified Rankin Scale, at one year.</p

Aspectos técnicos da monitorização da pressão intracraniana pelo método subaracnóideo no traumatismo craniencefálico grave Technical aspects of intracranial pressure monitoring by subarachnoid method in severe head injury

Foram analisados prospectivamente 206 pacientes com traumatismo craniencefálico (TCE) grave (8 pontos ou menos na Escala de Coma de Glasgow), internados na Unidade de Terapia Intensiva do Hospital das Clínicas da Universidade Estadual de Campinas. Após avaliação por tomografia computadorizada de crânio (TC), 72 pacientes necessitaram de tratamento neurocirúrgico. Todos os pacientes foram submetidos à monitorização contínua da pressão intracraniana (PIC) pelo método subaracnóideo (11 com parafuso metálico e 195 com cateter plástico). Os níveis de PIC foram registrados continuamente na tela do monitor, sendo os seus valores de final de hora anotados em ficha padronizada. Todos os pacientes foram tratados segundo um protocolo orientado pelos níveis da PIC. Não foram observadas complicações hemorrágicas ou hematomas intracranianos relacionados ao método de monitorização em TC de controle. Para controle de infecções intracranianas, foram colhidas amostras de líquido cefalorraquidiano através de punção lateral C1-C2 em 66 pacientes com PIC abaixo de 20 mm Hg, sendo positivas as culturas para Acinetobacter sp em 2 pacientes. O resultado final na alta hospitalar mostrou 75 (36,40%) óbitos e 131 (63,6%) sobreviventes. Os níveis de PIC influenciaram significativamente o resultado final (p<0,001), o que confirma a importância de sua monitorização e controle no tratamento do TCE grave. O método subaracnóideo para a monitorização contínua da PIC foi considerado aplicável, seguro, simples, de baixo custo e útil para a orientação do tratamento. A metodologia de registro da PIC foi considerada útil e prática. Apesar dos avanços técnicos nesta área, o método subaracnóideo mostrou-se uma alternativa bastante viável para a monitorização da PIC em pacientes com traumatismo craniencefálico grave.<br>Two hundred and six patients with severe head injury (Glasgow Coma Scale of 8 points or less after nonsurgical resuscitation on admission), managed at Intensive Care Unit-Hospital das Clínicas - Universidade Estadual de Campinas were prospectively analysed. All patients were assessed by CT scan and 72 required neurosurgical intervention. All patients were continuously monitored to evaluate intracranial pressure (ICP) levels by a subarachnoid device (11 with subarachnoid metallic bolts and 195 with subarachnoid polyvinyl catheters). The ICP levels were continuously observed in the bedside pressure monitor display and their end-hour values were recorded in a standard chart. The patients were managed according to a standard protocol guided by the ICP levels. There were no intracranial haemorrhagic complications or hematomas due the monitoring method. Sixty six patients were punctured by lateral C1-C2 technique to assess infectious complications and 2 had positive cerebrospinal fluid samples for Acinetobacter sp. The final results measured at hospital discharge showed 75 deaths (36,40%) and 131 (63,60%) survivors. ICP levels had significantly influenced the final results (p<0,001). The subarachnoid method to continuously assess the ICP levels was considered aplicable, safe, simple, low cost and useful to advise the management of the patients. The ICP record methodology was practical and useful. Despite the current technical advances the subarachnoid method was considered viable to assess the ICP levels in severe head injury

Severely malnourished children with a low weight-for-height have a higher mortality than those with a low mid-upper-arm-circumference: I. Empirical data demonstrates Simpson's paradox.

BACKGROUND:According to WHO childhood severe acute malnutrition (SAM) is diagnosed when the weight-for-height Z-score (WHZ) is <-3Z of the WHO2006 standards, the mid-upper-arm circumference (MUAC) is < 115 mm, there is nutritional oedema or any combination of these parameters. Recently there has been a move to eliminate WHZ as a diagnostic criterion on the assertion that children meeting the WHZ criterion are healthy, that MUAC is universally a superior prognostic indicator of mortality and that adding WHZ to the assessment does not improve the prediction; these assertions have lead to a controversy concerning the role of WHZ in the diagnosis of SAM.METHODS:We examined the mortality experience of 76,887 6-60 month old severely malnourished children admitted for treatment to in-patient, out-patient or supplementary feeding facilities in 18 African countries, of whom 3588 died. They were divided into 7 different diagnostic categories for analysis of mortality rates by comparison of case fatality rates, relative risk of death and meta-analysis of the difference between children admitted using MUAC and WHZ criteria.RESULTS:The mortality rate was higher in those children fulfilling the WHO2006 WHZ criterion than the MUAC criterion. This was the case for younger as well as older children and in all regions except for marasmic children in East Africa. Those fulfilling both criteria had a higher mortality. Nutritional oedema increased the risk of death. Having oedema and a low WHZ dramatically increased the mortality rate whereas addition of the MUAC criterion to either oedema-alone or oedema plus a low WHZ did not further increase the mortality rate. The data were subject to extreme confounding giving Simpson's paradox, which reversed the apparent mortality rates when children fulfilling both WHZ and MUAC criteria were included in the estimation of the risk of death of those fulfilling either the WHZ or MUAC criteria alone.CONCLUSIONS:Children with a low WHZ, but a MUAC above the SAM cut-off point are at high risk of death. Simpson's paradox due to confounding from oedema and mathematical coupling may make previous statistical analyses which failed to distinguish the diagnostic groups an unreliable guide to policy. WHZ needs to be retained as an independent criterion for diagnosis of SAM and methods found to identify those children with a low WHZ, but not a low MUAC, in the community.SCOPUS: ar.jinfo:eu-repo/semantics/publishe