Correlation of intra- and extraepidermal CD8 T cell numbers with development of psoriatic epidermal pathology

The development of psoriatic plaques is T cell dependent. Recently, Th17 CD4 T cells have been proposed to be the main effector cells. However, development of psoriasis is critically dependent on accumulation of epidermal T cells, among the majority express CD8. Here we show that numbers of epidermal CD8 T cells correlated with development of psoriasis in human biopsies, and that blockade of CD8 T cells by depleting antibodies inhibited development of psoriasis in the AGR xenotransplantation mouse model. In human dermis, both CD4 and CD8 T cell numbers correlated significantly with epidermal pathology, indicating a role for dermal CD4 T cells in orchestrating the development of psoriasiform changes induced by epidermis-infiltrating CD8 T cells.

Status epilepticus: an independent outcome predictor after cerebral anoxia.

BACKGROUND: Prognosis of status epilepticus (SE) depends on its cause, but there is uncertainty as to whether SE represents an independent outcome predictor for a given etiology. Cerebral anoxia is a relatively homogenous severe encephalopathy. Postanoxic SE is associated to a nearly 100% mortality in this setting; however, it is still unclear whether this is a severity marker of the underlying encephalopathy, or an independent factor influencing outcome. The goal of this study was to assess if postanoxic SE is independently associated with mortality after cerebral anoxia. METHODS: This was a retrospective observation of consecutive comatose survivors of cardiac arrest, including subjects treated with hypothermia. On the subgroup with EEG recordings in the first hospitalization days, univariate and multivariate analyses were applied to potential determinants of in-hospital mortality, and included the following variables: age, gender, type and length of cardiac arrest, occurrence of circulatory shock, presence of therapeutic hypothermia, and electrographic SE. RESULTS: Out of 166 postanoxic patients, 107 (64%) had an EEG (median latency from admission, 2 days); in this group, therapeutic hypothermia was administered in 59%. Death occurred in 71 (67%) patients. Postanoxic SE was associated with mortality regardless of type of acute cardiac rhythm and administration of hypothermic treatment. CONCLUSION: In this hospital-based cohort, postanoxic status epilepticus (SE) seems to be independently related to death in cardiac arrest survivors, suggesting that SE might determine a bad prognosis for a given etiology. Confirmation of these results in a prospective assessment is needed.

Transcultural adaptation and validation of the "Hip and Knee" questionnaire into Spanish.

BACKGROUND The purpose of the present study is to translate and validate the "Hip and Knee Outcomes Questionnaire", developed in English, into Spanish. The 'Hip and Knee Outcomes Questionnaire is a questionnaire planned to evaluate the impact in quality of life of any problem related to the human musculoskeletal system. 10 scientific associations developed it. METHODS The questionnaire underwent a validated translation/retro-translation process. Patients undergoing primary knee arthroplasty, before and six months postoperative, tested the final version in Spanish. Psychometric properties of feasibility, reliability, validity and sensitivity to change were assessed. Convergent validity with SF-36 and WOMAC questionnaires was evaluated. RESULTS 316 patients were included. Feasibility: a high number of missing items in questions 3, 4 and 5 were observed. The number of patients with a missing item was 171 (51.35%) in the preoperative visit and 139 (44.0%) at the postoperative. Internal validity: revision of coefficients in the item-rest correlation recommended removing question 6 during the preoperative visit (coefficient <0.20). Convergent validity: coefficients of correlation with WOMAC and SF-36 scales confirm the questionnaire's validity. Sensitivity to change: statistically significant differences were found between the mean scores of the first visit compared to the postoperative. CONCLUSION The proposed translation to Spanish of the 'Hip and Knee Questionnaire' is found to be reliable, valid and sensible to changes produced at the clinical practice of patients undergoing primary knee arthroplasty. However, some changes at the completion instructions are recommended. LEVEL OF EVIDENCE Level I. Prognostic study.

Mixed Blessing? EP Oversight of the ESDP and the Constitutional Treaty

As commonly held, the European Security and Defence Policy (ESDP) suffers from a “double democratic deficit”: the EP has a marginal role in the ESDP-making process and the national parliaments remain unable to account for their own government. Therefore pressure coming from these two institutions had been exercised during the Convention on the Future of Europe to improve the democratic oversight on this rapidly evolving policy. This paper investigates the innovations included in the Constitutional Treaty, focusing specifically on the new role granted to the EP. It shows that even though this text does not substantially modify the inter-institutional balance of powers in the ESDP area, the EP may take advantage of some of its articles to become an actor in the ESDP-control process in the ‘living constitution.

Correlation between TH1 response standard cytokines as biomarkers in patients with the delta virus in the western Brazilian Amazon

Hepatitis D virus (HDV) is endemic in the Amazon Region and its pathophysiology is the most severe among viral hepatitis. Treatment is performed with pegylated interferon and the immune response appears to be important for infection control. HDV patients were studied: untreated and polymerase chain reaction (PCR) positive (n = 9), anti-HDV positive and PCR negative (n = 8), and responders to treatment (n = 12). The cytokines, interleukin (IL)-2 (p = 0.0008) and IL-12 (p = 0.02) were differentially expressed among the groups and were also correlated (p = 0.0143). Future studies will be conducted with patients at different stages of treatment, associating the viral load with serum cytokines produced, thereby attempting to establish a prognostic indicator of the infection.

Lack of correlation between the optimal glycaemic control and coronary micro vascular dysfunction in patients with diabetes mellitus: a cross sectional study.

Background Coronary microvascular dysfunction (CMD) is associated with cardiovascular events in type 2 diabetes mellitus (T2DM). Optimal glycaemic control does not always preclude future events. We sought to assess the effect of the current target of HBA1c level on the coronary microcirculatory function and identify predictive factors for CMD in T2DM patients. Methods We studied 100 patients with T2DM and 214 patients without T2DM. All of them with a history of chest pain, non-obstructive angiograms and a direct assessment of coronary blood flow increase in response to adenosine and acetylcholine coronary infusion, for evaluation of endothelial independent and dependent CMD. Patients with T2DM were categorized as having optimal (HbA1c < 7 %) vs. suboptimal (HbA1c ≥ 7 %) glycaemic control at the time of catheterization. Results Baseline characteristics and coronary endothelial function parameters differed significantly between T2DM patients and control group. The prevalence of endothelial independent CMD (29.8 vs. 39.6 %, p = 0.40) and dependent CMD (61.7 vs. 62.2 %, p = 1.00) were similar in patients with optimal vs. suboptimal glycaemic control. Age (OR 1.10; CI 95 % 1.04–1.18; p < 0.001) and female gender (OR 3.87; CI 95 % 1.45–11.4; p < 0.01) were significantly associated with endothelial independent CMD whereas glomerular filtrate (OR 0.97; CI 95 % 0.95–0.99; p < 0.05) was significantly associated with endothelial dependent CMD. The optimal glycaemic control was not associated with endothelial independent (OR 0.60, CI 95 % 0.23–1.46; p 0.26) or dependent CMD (OR 0.99, CI 95 % 0.43–2.24; p = 0.98). Conclusions The current target of HBA1c level does not predict a better coronary microcirculatory function in T2DM patients. The appropriate strategy for prevention of CMD in T2DM patients remains to be addressed. Keywords: Endothelial dysfunction; Diabetes mellitus; Coronary microcirculation

Prognosis Relevance of Serum Cytokines in Pancreatic Cancer.

The overall survival of patients with pancreatic ductal adenocarcinoma is extremely low. Although gemcitabine is the standard used chemotherapy for this disease, clinical outcomes do not reflect significant improvements, not even when combined with adjuvant treatments. There is an urgent need for prognosis markers to be found. The aim of this study was to analyze the potential value of serum cytokines to find a profile that can predict the clinical outcome in patients with pancreatic cancer and to establish a practical prognosis index that significantly predicts patients' outcomes. We have conducted an extensive analysis of serum prognosis biomarkers using an antibody array comprising 507 human cytokines. Overall survival was estimated using the Kaplan-Meier method. Univariate and multivariate Cox's proportional hazard models were used to analyze prognosis factors. To determine the extent that survival could be predicted based on this index, we used the leave-one-out cross-validation model. The multivariate model showed a better performance and it could represent a novel panel of serum cytokines that correlates to poor prognosis in pancreatic cancer. B7-1/CD80, EG-VEGF/PK1, IL-29, NRG1-beta1/HRG1-beta1, and PD-ECGF expressions portend a poor prognosis for patients with pancreatic cancer and these cytokines could represent novel therapeutic targets for this disease.

C-reactive protein, procalcitonin, lactate and score apache II in septic patients' prognosis.

Background: APACHE-II IS a score, based on several clinical and analytical measurements within 24 hours of admission in Intensive Care Unit (ICU). C-Reactive Protein (CRP), Lactate and recently Procalcitonin (PCT), also are biomarkers for the assessment of septic patients. The aim of this study was to find out if CRP, lactate and PCT during the first 24 hours from severe sepsis or septic shock onset, improved prediction of the APACHE II in terms of prognosis. Conclusions: CRP improves the prediction of patients with sepsis used in conjunction with the APACHE II score in severe sepsis and, lactate along with the CRP are the best precictors of survival in the cases of septic shock. The PCT did not show any predictive value.

Cancer testis antigen expression in gastrointestinal stromal tumors: new markers for early recurrence.

Cancer testis antigens (CTAs) are expressed in a variety of malignant tumors but not in any normal adult tissues except germ cells and occasionally placenta. Because of this tumor-associated pattern of expression, CTAs are regarded as potential vaccine targets. The expression of CTAs in gastrointestinal stromal tumors (GIST) has not been analyzed systematically previously. The present study was performed to analyze the expression of CTA in GIST and to determine if CTA expression correlates with prognosis. Thirty-five GIST patients were retrospectively analyzed for their expression of CTAs by immunohistochemistry using the following monoclonal antibodies (mAb/antigen): MA454/MAGE-A1, M3H67/MAGE-A3, 57B/MAGE-A4, CT7-33/MAGE-C1 and E978/NY-ESO-1. Fourteen tumors (40%) expressed 1 or more of the 5 CTAs tested. Fourteen percent (n = 5/35) were positive for MAGE-A1, MAGE-A3 or MAGE-A4, respectively. Twenty-six percent (n = 9/35) stained positive for MAGE-C1 and 20% (n = 7/35) for NY-ESO-1. A highly significant correlation between CTA expression and tumor recurrence risk was observed (71% vs. 29%; p = 0.027). In our study population, the high-risk GIST expressed CTAs more frequently than low-risk GIST (p = 0.012). High-risk GISTs which stained positive for at least 1 CTA, recurred in 100% (n = 25) of the cases. This is the first study analyzing CTA expression in GIST and its prognostic value for recurrence. The CTA staining could add information to the individual patient prognosis and represent an interesting target for future treatment strategies.

Impact of additional cytogenetic aberrations at diagnosis on prognosis of CML: long-term observation of 1151 patients from the randomized CML Study IV.

The prognostic relevance of additional cytogenetic findings at diagnosis of chronic myeloid leukemia (CML) is unclear. The impact of additional cytogenetic findings at diagnosis on time to complete cytogenetic (CCR) and major molecular remission (MMR) and progression-free (PFS) and overall survival (OS) was analyzed using data from 1151 Philadelphia chromosome-positive (Ph(+)) CML patients randomized to the German CML Study IV. At diagnosis, 1003 of 1151 patients (87%) had standard t(9;22)(q34;q11) only, 69 patients (6.0%) had variant t(v;22), and 79 (6.9%) additional cytogenetic aberrations (ACAs). Of these, 38 patients (3.3%) lacked the Y chromosome (-Y) and 41 patients (3.6%) had ACAs except -Y; 16 of these (1.4%) were major route (second Philadelphia [Ph] chromosome, trisomy 8, isochromosome 17q, or trisomy 19) and 25 minor route (all other) ACAs. After a median observation time of 5.3 years for patients with t(9;22), t(v;22), -Y, minor- and major-route ACAs, the 5-year PFS was 90%, 81%, 88%, 96%, and 50%, and the 5-year OS was 92%, 87%, 91%, 96%, and 53%, respectively. In patients with major-route ACAs, the times to CCR and MMR were longer and PFS and OS were shorter (P < .001) than in patients with standard t(9;22). We conclude that major-route ACAs at diagnosis are associated with a negative impact on survival and signify progression to the accelerated phase and blast crisis.

Clinical and epidemiological features and prognosis of complicated pyelonephritis: a prospective observational single hospital-based study.

BACKGROUND Complicated pyelonephritis (cPN), a common cause of hospital admission, is still a poorly-understood entity given the difficulty involved in its correct definition. The aim of this study was to analyze the main epidemiological, clinical, and microbiological characteristics of cPN and its prognosis in a large cohort of patients with cPN. METHODS We conducted a prospective, observational study including 1325 consecutive patients older than 14 years diagnosed with cPN and admitted to a tertiary university hospital between 1997-2013. After analyzing the main demographic, clinical and microbiological data, covariates found to be associated with attributable mortality in univariate analysis were included in a multivariate logistic regression model. RESULTS Of the 1325 patients, 689 (52%) were men and 636 (48%) women; median age 63 years, interquartile range [IQR] (46.5-73). Nine hundred and forty patients (70.9%) had functional or structural abnormalities in the urinary tract, 215 (16.2%) were immunocompromised, 152 (11.5%) had undergone a previous urinary tract instrumentation, and 196 (14.8%) had a long-term bladder catheter, nephrostomy tube or ureteral catheter. Urine culture was positive in 813 (67.7%) of the 1251 patients in whom it was done, and in the 1032 patients who had a blood culture, 366 (34%) had bacteraemia. Escherichia coli was the causative agent in 615 episodes (67%), Klebsiella spp in 73 (7.9%) and Proteus ssp in 61 (6.6%). Fourteen point one percent of GNB isolates were ESBL producers. In total, 343 patients (25.9%) developed severe sepsis and 165 (12.5%) septic shock. Crude mortality was 6.5% and attributable mortality was 4.1%. Multivariate analysis showed that an age >75 years (OR 2.77; 95% CI, 1.35-5.68), immunosuppression (OR 3.14; 95% CI, 1.47-6.70), and septic shock (OR 58.49; 95% CI, 26.6-128.5) were independently associated with attributable mortality. CONCLUSIONS cPN generates a high morbidity and mortality and likely a great consumption of healthcare resources. This study highlights the factors directly associated with mortality, though further studies are needed in the near future aimed at identifying subgroups of low-risk patients susceptible to outpatient management.

The lincRNA HOTAIRM1, located in the HOXA genomic region, is expressed in acute myeloid leukemia, impacts prognosis in patients in the intermediate-risk cytogenetic category, and is associated with a distinctive microRNA signature.

Long non-coding RNAs (lncRNAs) are deregulated in several tumors, although their role in acute myeloid leukemia (AML) is mostly unknown.We have examined the expression of the lncRNA HOX antisense intergenic RNA myeloid 1 (HOTAIRM1) in 241 AML patients. We have correlated HOTAIRM1 expression with a miRNA expression profile. We have also analyzed the prognostic value of HOTAIRM1 expression in 215 intermediate-risk AML (IR-AML) patients.The lowest expression level was observed in acute promyelocytic leukemia (P < 0.001) and the highest in t(6;9) AML (P = 0.005). In 215 IR-AML patients, high HOTAIRM1 expression was independently associated with shorter overall survival (OR:2.04;P = 0.001), shorter leukemia-free survival (OR:2.56; P < 0.001) and a higher cumulative incidence of relapse (OR:1.67; P = 0.046). Moreover, HOTAIRM1 maintained its independent prognostic value within the favorable molecular subgroup (OR: 3.43; P = 0.009). Interestingly, HOTAIRM1 was overexpressed in NPM1-mutated AML (P < 0.001) and within this group retained its prognostic value (OR: 2.21; P = 0.01). Moreover, HOTAIRM1 expression was associated with a specific 33-microRNA signature that included miR-196b (P < 0.001). miR-196b is located in the HOX genomic region and has previously been reported to have an independent prognostic value in AML. miR-196b and HOTAIRM1 in combination as a prognostic factor can classify patients as high-, intermediate-, or low-risk (5-year OS: 24% vs 42% vs 70%; P = 0.004).Determination of HOTAIRM1 level at diagnosis provided relevant prognostic information in IR-AML and allowed refinement of risk stratification based on common molecular markers. The prognostic information provided by HOTAIRM1 was strengthened when combined with miR-196b expression. Furthermore, HOTAIRM1 correlated with a 33-miRNA signature.

Predictive value of Glasgow Coma Scale after brain trauma: change in trend over the past ten years.

BACKGROUND: Age and the Glasgow Coma Scale (GCS) score on admission are considered important predictors of outcome after traumatic brain injury. We investigated the predictive value of the GCS in a large group of patients whose computerised multimodal bedside monitoring data had been collected over the previous 10 years. METHODS: Data from 358 subjects with head injury, collected between 1992 and 2001, were analysed retrospectively. Patients were grouped according to year of admission. Glasgow Outcome Scores (GOS) were determined at six months. Spearman's correlation coefficients between GCS and GOS scores were calculated for each year. RESULTS: On average 34 (SD: 7) patients were monitored every year. We found a significant correlation between the GCS and GOS for the first five years (overall 1992-1996: r = 0.41; p<0.00001; n = 183) and consistent lack of correlations from 1997 onwards (overall 1997-2001: r = 0.091; p = 0.226; n = 175). In contrast, correlations between age and GOS were in both time periods significant and similar (r = -0.24 v r = -0.24; p<0.002). CONCLUSIONS: The admission GCS lost its predictive value for outcome in this group of patients from 1997 onwards. The predictive value of the GCS should be carefully reconsidered when building prognostic models incorporating multimodality monitoring after head injury.

Traitement pharmacologique de l'état de mal réfractaire [Drug treatment of refractory status epilepticus]

Status epilepticus (SE) refractory to benzodiazepines and other antiepileptic agents is managed with intravenous anesthetic compounds, such as thiopental, propofol or midazolam. These drugs display quite different pharmacodynamic and pharmacokinetic properties, but have not been prospectively compared to date. Their use is clearly advocated for the treatment of generalized convulsive SE, whereas partial-complex, or absence SE are generally managed less aggressively, in consideration of their better prognosis. The most important aspect seems to be related to the correct use of these anesthetics in the right context, rather than the choice of one specific compound. An electroencephalographic burst-suppression should be targeted for about 24hour, before progressive weaning of the dosage under EEG monitoring. If this approach proves unsuccessful, the use of other drugs, including inhalational anesthetics, has been described.