Independent Predictor Of Unfavorable Outcome Research Articles

Prediction of Functional Outcome in Ischemic Stroke Patients: An Observational Study on Egyptian Population

IntroductionDetermining the prognosis of ischemic stroke is important for neurologists and patients. The aim is to study the predictors of three months clinical outcome in ischemic stroke patients.Materials and methodsA total of 397 patients were classified according to three months modified Rankin Scale score (mRS score) into two groups, favorable and unfavorable outcome. Favorable outcome was assumed if the score was zero or one, or unchanged if the score was ≥ 1 before the onset of the most recent event.ResultsThe variables associated with unfavorable outcome were old age (P <0.001), presence of cardiac disease (P <0.001), low ejection fraction (P=0.008), low levels of total cholesterol and low-density lipoproteins (P <0.001), large artery atherosclerosis stroke (P <0.001), early confluent (P=0.005), high National Institute of Health stroke scale (NIHSS) score on admission (P <0.001), mRS score before admission (P <0.001), mRS score on discharge (P <0.001). Lacunar stroke was associated with favorable outcome (P <0.001). The regression analysis showed mRS score on discharge (P <0.001) and the presence of cardiac diseases (P=0.077) as independent predictors of unfavorable outcome.ConclusionHigh mRS score on discharge and presence of the cardiac disease independently could predict the unfavorable outcome and mRS score on discharge had a high sensitivity and negative predictive value in predicting the unfavorable outcome.AbbreviationsMRS: score modified Rankin scale score, NIHSS: National Institutes of Health Stroke Scale, MRI: Magnetic resonance imaging, LDL: Low-density lipoprotein, MRA: Magnetic resonance of arteries.

Predictive value of serum transthyretin for outcome in acute ischemic stroke.

IntroductionThe impact of choroid plexus with its blood–cerebrospinal fluid barrier in the ischemic stroke pathology is poorly explored. Transthyretin (TTR) is a protein synthesized in liver and just in choroid plexus.ObjectivesThe current study was designed to assess the prognostic value of serum TTR for functional outcome (at the time of hospital discharge) and long-term (one-year) overall mortality in ischemic stroke patients.Patients and methodsWe conducted a prospective observational study. Patients (n = 81) with acute (< 24 hours of symptoms onset) ischemic stroke consecutively admitted to Stroke Unit were included. An unfavorable outcome was defined as a modified Rankin Scale (mRS) score ≥ 3. The relationships between serum TTR levels and clinical outcome were analyzed using multivariate analysis. One-year mortality was analyzed by Kaplan–Meier survival curves stratified by mean value of TTR.ResultsCompared with patients with mRS <3, patients with an unfavorable outcome at hospital discharge had significantly lower TTR levels on admission (P < 0.0001). In non-survivals serum TTR levels were significantly lower compared with patients who survive one year of observation (P = 0.009). Using multivariate analysis, transthyretin emerged as an independent predictor for unfavorable outcome at the day of hospital discharge (adjusted odds ratio = 0.96; 95% CI: 0.9–0.99, P <0.05). A one-year mortality of patients with the lower TTR levels was significantly higher than in patients with TTR levels above mean value (P = 0.02).ConclusionsSerum level of TTR at admission was a predictor of functional outcome after ischemic stroke and was also associated with one-year mortality in stroke survivals.

Presentation and outcome of patients with 2016 WHO diagnosis of prefibrotic and overt primary myelofibrosis

AbstractThe 2016 revision of the World Health Organization (WHO) classification of myeloproliferative neoplasms defines 2 stages of primary myelofibrosis (PMF): prefibrotic/early (pre-PMF) and overt fibrotic (overt PMF) phase. In this work, we studied the clinical and molecular features of patients belonging to these categories of PMF. The diagnosis of 661 PMF patients with a bone marrow biopsy at presentation was revised according to modern criteria; clinical information and annotation of somatic mutations in both driver and selected nondriver myeloid genes were available for all patients. Compared with pre-PMF, overt PMF was enriched in patients with anemia, thrombocytopenia, leukopenia, higher blast count, symptoms, large splenomegaly, and unfavorable karyotype. The different types of driver mutations were similarly distributed between the 2 categories, whereas selected mutations comprising the high mutation risk (HMR) category (any mutations in ASXL1, SRSF2, IDH1/2, EZH2) were more represented in overt PMF. More patients with overt PMF were in higher International Prognostic Scoring System risk categories at diagnosis, and the frequency increased during follow-up, suggesting greater propensity to disease progression compared with pre-PMF. Median survival was significantly shortened in overt PMF (7.2 vs 17.6 years), with triple negativity for driver mutations and presence of HMR mutations representing independent predictors of unfavorable outcome. The findings of this “real-life” study indicate that adherence to 2016 WHO criteria allows for identification of 2 distinct categories of patients with PMF where increased grades of fibrosis are associated with more pronounced disease manifestations, adverse mutation profile, and worse outcome, overall suggesting they might represent a phenotypic continuum.

Elevated mean platelet volume is associated with poor outcome after mechanical thrombectomy

BackgroundElevated mean platelet volume (MPV), indicating higher platelet activity, could be a predictor of prognosis in patients with acute ischemic stroke receiving medical therapy.ObjectiveTo investigate the relationship between MPV and...

Anticoagulation Therapy in Patients Suffering from Aneurysmal Subarachnoid Hemorrhage: Influence on Functional Outcome-a Single-Center Series and Multivariate Analysis.

Favorable outcome in patients presenting with aneurysmal subarachnoid hemorrhage (SAH) is determined by several factors. Nevertheless, data on the influence of prior use of oral anticoagulation drugs on functional outcome in patients suffering from SAH are scarce. We therefore analyzed our institutional data. From January 2009 to October 2015, 480 patients suffering from aneurysmal SAH were admitted to our institution. Information including patient characteristics, treatment modality, aneurysm size and location, radiologic features, and functional neurologic outcome was assessed and further analyzed. Outcome was assessed according to the modified Rankin Scale (mRS) at 6 months and stratified into favorable (mRS 0-2) versus unfavorable (mRS 3-6). Overall, 17 of 480 patients suffering from aneurysmal SAH were on anticoagulation therapy before ictus (4%). Patients without anticoagulation therapy were significantly younger compared with patients with anticoagulation therapy before SAH (P= 0.005). Furthermore, patients without anticoagulation therapy presented in a significantly better clinical condition compared with patients with anticoagulation therapy before SAH (P=0.02). Additionally, patients without anticoagulation therapy achieved significantly more often favorable functional outcome compared with patients with anticoagulation therapy before SAH (P= 0.02). However, anticoagulation therapy was not identified as a significant and independent predictor for unfavorable outcome in the multivariate logistic regression analysis. Anticoagulation therapy has not been identified as a significant and independent factor influencing functional outcome in patients suffering from SAH. Therefore treatment should not be omitted. Nevertheless, cautious management is necessary in patients with known anticoagulation therapy before SAH.

Sex-based differences in adults with community-acquired bacterial meningitis: a prospective cohort study

ObjectivesTo investigate sex-based differences in clinical features, causative pathogens, outcome and treatment of adult community-acquired meningitis. MethodsFrom January 2006 to July 2014, we prospectively investigated sex-based differences in clinical features, causative pathogens, outcome and treatment of adult community-acquired meningitis in a nationwide cohort study in the Netherlands. Sex was analysed along with known predictors of unfavourable outcome using logistic regression. ResultsWe evaluated 1412 episodes of meningitis, 707 (50%) in men. Men more often presented with a history of remote head injury (41/667 (6%) versus 14/658 (2%) women, p 0.0002) or alcoholism (61/652 (9%) versus 21/660 (3%) women, p <0.0001). Neck stiffness was less common in men (453/651 (70%) versus 524/671 (78%) women, p 0.0004). Despite greater illness severity, women were less likely to receive treatment in an intensive care unit (odds ratio (OR) 0.72, 95% CI 0.58–0.89, p 0.003) or mechanical ventilation (OR 0.67, 95% CI 0.54–0.85, p 0.001). Women exhibited higher serum inflammatory parameters than men (median C-reactive protein 211 versus 171, p 0.0001; median erythrocyte sedimentation rate 48 versus 33, p <0.0001). Corticosteroids improved prognosis in both sexes, but absolute risk reduction was higher in women (20% versus 15%, p 0.001), although we found no significant interaction between sex and dexamethasone (p 0.38). In the multivariable analysis, male sex was an independent predictor of unfavourable outcome (OR 1.34, 95% CI 1.03–1.75, p 0.03) and death (OR 1.47, 95% CI 1.04–2.07, p 0.03). ConclusionsOur findings show sex-based differences in adults with community-acquired bacterial meningitis. Male sex is an independent risk factor for adverse outcome. It is possible that sex-based differences in immune reaction could determine a distinct response to corticosteroids.

Initial intracranial pressure as a prognosticator in head-injured patients undergoing decompressive craniectomy.

PurposeTo examine the prognostic discrimination and prediction of initial intracranial pressure (ICP) in patients with traumatic brain injury (TBI) undergoing decompressive craniectomy (DC).ResultsThe relationship between the initial ICP value and prognosis was quantified, and higher values indicated worse patient outcomes. Univariate analysis showed that the initial ICP value was significantly associated with mortality (odds ratio: 1.272, 95% confidence interval: 1.116-1.449; P<0.001) and unfavorable outcomes (odds ratio: 1.256, 95% confidence interval: 1.160-1.360; P<0.001). After adjustment for related outcome predictors of TBI in multivariate regression, the initial ICP value remained an independent predictor of unfavorable outcomes (odds ratio: 1.251, 95% confidence interval: 1.140-1.374; P=0.015) and mortality (odds ratio: 1.162, 95% confidence interval: 1.093-1.321; P=0.019).MethodsA retrospective study was conducted in 133 TBI patients after DC. Initial ICP was defined as the first ICP recorded during surgery. Mortality and Glasgow Outcome Scale score at the end of follow-up were used as outcome measures. Unfavorable and favorable outcomes were classified by a Glasgow Outcome Scale score of 1 to 3 and 4 to 5, respectively. We used binary logistic and proportional odds regression for prognostic analyses.ConclusionFor TBI patients undergoing DC, the initial ICP value provides great prognostic discrimination and is an independent predictor of unfavorable outcomes and mortality. We suggest that the initial ICP be included as a prognosticator in the overall assessment of prognosis of head-injured patients after DC.

Autoimmunity and Prognosis of Patients With Morphologically Documented Myocarditis

to assess clinical and prognostic value of circulating cardiospecific autoantibodies (AAB) and CD4+ T-regulatory cells in patients with myocarditis. We included into this study 47 patients with lymphocytic myocarditis verified by analysis of histological and immunohistochemical data. Comparison group consisted of 30 practically healthy persons. Content of marker cardiotropic AAT were measured with the help of standardized immune enzyme test-systems. Number of circulating CD4+CD25+ and CD4+CD25+FoxP3+ T-lymphocytes were evaluated by flow cytometry. Among factors determining prognosis of patients with lymphocytic myocarditis factors of key significance were the presence of clinically overt heart failure at the disease debut, and degree of reduction of left ventricular ejection fraction. Distinctive feature of active myocarditis was elevation of titer of AABs to sarcomeric, cytoskeleton, and cytoplasmic proteins of cardiomyocytes, as well as elevated level of AABs to various epitopes of adenine nucleotide translocator. Elevated level of AAB to 1-adrenoreceptors was an independent predictor of unfavorable outcome in patients with lymphocytic myocarditis. Increased population of circulating CD4+CD25+ T-regulatory cells was as sociated with elevated concentration of of natriuretic peptide. Abnormalities in the system of autoimmunity play key role not only in pathogenesis but also in prognosis of inflammatory myocardial diseases. Changes of profile of circulating cardiospecific AABs and T-regulatory cells can bear a protective function.

Phosphatase PPM1A is a novel prognostic marker in pancreatic ductal adenocarcinoma

Pancreatic ductal adenocarcinoma (PDAC) harbors complex molecular alterations and remains a lethal disease. Aberrant TGF-β/Smads signaling is a well-known mechanism involved in the progression of PDACs. However, loss of Smad4 expression is reported in only ~50% of PDACs and is generally associated with worse prognosis. Investigating additional prognostic markers is warranted. PPM1A is a phosphatase that dephosphorylates TGF-β-activated Smad2/3 and inactivates the TGF-β signaling. Little is known about the clinical significance of PPM1A in PDACs and its functional relationship to Smad4. In this study, PPM1A and Smad4 immunohistochemistry was assessed in 180 R0 resected human PDACs. PPM1A was lost in 41.7% cases, whereas Smad4 was lost in 45.7% cases. The median survival rate with negative and positive PPM1A was 10.9 and 16.8 months, respectively. Loss of PPM1A was significantly associated with larger tumor size and higher stage and was an independent predictor of unfavorable outcomes. Intriguingly, the overall survival of this cohort was divided into 3 groups based on the expression pattern of PPM1A and Smad4, with the Smad4+/PPM1A+ pattern associated with favorable survival, the Smad4+/PPM1A- or Smad4-/PPM1A- pattern associated with unfavorable, and the PPM1A+/Smad4- pattern fell between these 2 groups. In 82 cases with negative Smad4, PPM1A or P-Smad2/3 expression was retained. Using a SMAD4-deficient human PDAC cell line, BxPC3, we further demonstrated that TGF-β1 treatment induced PPM1A and P-Smad2/3 expression in this cell line. PPM1A and Smad4 immunohistochemistry in surgical specimens may provide more accurate prognostic stratification for patients with PDAC.

Feasibility, Reliability and Predictive Value Of In-Ambulance Heart Rate Variability Registration

BackgroundHeart rate variability (HRV) is a parameter of autonomic nervous system function. A decrease of HRV has been associated with disease severity, risk of complications and prognosis in several conditions.ObjectiveWe aim to investigate the feasibility and the reliability of in-ambulance HRV registration during emergency interventions, and to evaluate the association between prehospital HRV parameters, patient characteristics, vital parameters and short-term outcome.MethodsWe conducted a prospective study using a non-invasive 2-lead ECG registration device in 55 patients transported by the paramedic intervention team of the Universitair Ziekenhuis Brussel. HRV assessment included time domain parameters, frequency domain parameters, nonlinear analysis, and time-frequency analysis. The correlation between HRV parameters and patient and outcome characteristics was analyzed and compared to controls.ResultsArtifact and ectopic detection rates were higher in patients during ambulance transportation compared to controls in resting conditions, yet technical reasons precluding in-ambulance HRV analysis occurred in only 9.6% of cases. HRV acquisition was possible without safety issues or interference with routine emergency care. Reliability of the results was considered sufficient for Sample entropy (SampEn), good for the ratio of low frequency and high frequency components (LF/HF ratio) in the frequency and the time frequency domain, and excellent for the triangular interpolation of the NN interval histogram (TINN), and for the short-term scaling exponent of the detrended fluctuation analysis (DFA α1). HRV indices were significantly reduced inpatients with unfavorable outcome compared to patients with favorable outcome and controls. Multivariate analysis identified lower DFA α1 as an independent predictor of unfavorable outcome (OR, 0.155; 95% CI 0.024–0.966; p = 0.049).ConclusionIn-ambulance HRV registration is technically and operationally feasible and produces reliable results for parameters in the time, frequency, nonlinear and time frequency domain. Especially non-linear HRV analysis during emergency ambulance transportation may be a promising approach to predict patient outcome.

MDR-TB Outbreak among HIV-Negative Tunisian Patients followed during 11 Years.

BackgroundMultidrug-resistant tuberculosis (MDR-TB) outbreaks that evolve, from the outset, in a context strictly negative for HIV infection deserve special consideration since they reflect the true intrinsic epidemic potential of the causative strain. To our knowledge, the long-term evolution of such exceptional outbreaks and the treatment outcomes for the involved patients has never been reported hitherto. Here we provide a thorough description, over an 11-year period, of an MDR-TB outbreak that emerged and expanded in an HIV-negative context, Northern Tunisia.Methodology/Principal FindingsFrom October 2001 to June 2011, the MDR-TB outbreak involved 48 HIV-negative individuals that are mainly young (mean age 31.09 yrs; 89.6% male) and noninstitutionalized. Drug susceptibility testing coupled to mutational analysis revealed that initial transmission involved an isolate that was simultaneously resistant to isoniazid, rifampicin, ethambutol, and streptomycin. The causative Haarlem3-ST50 outbreak strain expanded mainly as an 11-banded IS6110 RFLP profile (77.1%), from which a 12-banded subclone evolved. After undergoing a 2-year treatment with second-line drugs, 22 (45.8%) patients were cured and 3 (6.2%) completed treatment, thus yielding an overall treatment success rate of 52.1%. Among the patients that experienced unfavorable treatment outcomes, 10 (20.8%) failed treatment, 3 (6.2%) were lost to follow-up, 5 (10.4%) died, and 5 (10.4%) could not be evaluated. Poor adherence to treatment was found to be the main independent predictor of unfavorable outcomes (HR: 9.15; 95% CI 1.72–48.73; P = 0.014). Intriguingly, the evolved 12-banded subclone proved significantly associated with unfavorable outcomes (HR: 4.90; 95% CI 1.04–23.04, P = 0.044). High rate of fatality and relapse was further demonstrated at the long-term, since 70% of those whose treatment failed have died, and 24% among those deemed successfully treated have relapsed.Conclusions/SignificanceTaken together, the data obtained in this study indicate that MDR-TB clinical isolates could become fit enough to cause large and severe outbreaks in an HIV-negative context. Such MDR-TB outbreaks are characterized by low treatment success rates and could evolve towards increased severity, thus calling for early detection of cases and the necessity to raise the bar of surveillance throughout and beyond the treatment period.

Glycosylated Hemoglobin and Functional Outcome after Acute Ischemic Stroke

Diabetes mellitus (DM) is associated to an increased incidence of cerebral and myocardial infarction which could be reduced by long-term maintenance of optimal glycemic values. The aim of the study was to evaluate in diabetic patients with ischemic stroke the chronic glycemic status and its relationship with functional outcome. We retrospectively identified consecutive diabetic patients hospitalized for acute ischemic stroke. Clinical and biochemical characteristics at admission were assessed. The outcome measures were the attainment of the recommended glycosylated hemoglobin A1 (HbA1c) level and the 3-month functional status according to the modified Rankin Scale score. Among the 112 enrolled patients, 39 (34.8%) met the recommended goal of HbA1c less than 7%. Higher education level was predictive of good prestroke glycemic control (adjusted OR 1.32 per year [95% CI 1.15-1.51], P < .001). At the 3-month evaluation, 44 (39.3%) patients were classified as having a poor outcome. After categorization of HbA1c values into tertiles, a dose-response relationship with poor functional recovery was found (P = .001). The suboptimal prestroke glycemic status was an independent predictor of unfavorable outcome (adjusted OR 6.22 [95% CI 1.94-19.98] for HbA1c ≥7%, P = .002). The management of DM was suboptimal in nearly two thirds of diabetic subjects presenting with acute ischemic stroke. The glycemic control before stroke occurrence was an independent prognostic factor and HbA1c values above the recommended goals increased the risk of unfavorable 3-month outcome. The improvement of DM management may be an effective strategy to either decrease the burden of cerebrovascular disease or influence its clinical course.

Lack of improvement following endovascular therapy in patients with acute ischemic stroke

Background: Recent randomized trials have consistently demonstrated a clinical benefit of endovascular therapy (ET) over best medical therapy (including intravenous (IV) thrombolysis in eligible patients) or IV thrombolysis only in selected patients with acute ischemic stroke (AIS) due to proximal occlusion in the carotid territory. Previous study demonstrates that lack of improvement (LOI) at 24 hours is an independent predictor of poor outcome and death at 3 months in patients with AIS treated with IV alteplase. However, LOI at 24 hours following ET has not been studied systematically. The purpose of this study is to identify predictors of LOI at 24 hours in patients with AIS after ET as well as the relationship between LOI and unfavorable outcome at 3 months. Methods: A total of 98 consecutive patients with AIS treated with ET in two separate stroke centers from 2010 to 2014 were retrospectively reviewed. Data on demographics, preexisting vascular risk factors, occlusion site, pre- and post-treatment modified Treatment in Cerebral Ischemia (mTICI) classification, collaterals and National Institutes of Health Stroke Scale (NIHSS) score on admission as well as 24 hours after the endovascular procedurals were collected. LOI was defined as a reduction of 3 points or less on the NIHSS at 24 hours compared with baseline. A 3-month functional outcome was assessed using the modified Rankin scale (mRS). Unfavorable outcome was prespecified as a score of more than 2 on the mRS. The onset-to-reperfusion time (ORT) was defined as time to mTICI 2b or 3 or end of procedure. Long ORT was defined as time to reperfusion beyond 6 hours. Poor reperfusion was defined as mTICI ≦2a. The pretreatment collateral circulation extent was graded as poor (grades 0–1) or good (grades 2–4). Results: Among the 98 patients with AIS who were treated with ET, LOI was present in 48 (49%) subjects. Multivariate analysis indicated that poor collaterals (odds ratio [OR] 3.25; 95% confidence interval [CI]: 1.29–8.19; p = 0.012) and long ORT (OR 3.97, 95% CI: 1.66–9.54; p = 0.002) were independent predictors of LOI. LOI (OR 7.18, 95% CI: 2.39–21.61; p < 0.001) was independently associated with unfavorable outcome at 3 months. Conclusion: Among patients with AIS treated with ET, as an independent predictor of unfavorable outcome, LOI at 24 hours is associated with poor collaterals and long ORT.

Predictors of Postoperative Seizure Recurrence: A Longitudinal Study of Temporal and Extratemporal Resections.

Objective. We investigated the longitudinal outcome of resective epilepsy surgery to identify the predictors of seizure recurrence. Materials and Methods. We retrospectively analyzed patients who underwent resections for intractable epilepsy over a period of 7 years. Multiple variables were investigated as potential predictors of seizure recurrence. The time to first postoperative seizure was evaluated using survival analysis and univariate analysis at annual intervals. Results. Among 70 patients, 54 (77%) had temporal and 16 (23%) had extratemporal resections. At last follow-up (mean 48 months; range 24–87 months), the outcome was Engel class I in 84% (n = 59) of patients. Seizure recurrence followed two patterns: recurrence was “early” (within 2 years) in 82% of patients, of whom 83% continued to have seizures despite optimum medical therapy; recurrence was “late” (after 2 years) in 18%, of whom 25% continued to have seizures subsequently. Among the variables of interest, only resection site and ictal EEG remained as independent predictors of seizure recurrence over the long term (p < 0.05). Extratemporal resection and discordance between ictal EEG and resection area were associated with 4.2-fold and 5.6-fold higher risk of seizure recurrence, respectively. Conclusions. Extratemporal epilepsy and uncertainty in ictal EEG localization are independent predictors of unfavorable outcome. Seizure recurrence within two years of surgery indicates poor long-term outcome.

Elderly Patients with Severe Traumatic Brain Injury Could Benefit from Surgical Treatment

In elderly patients with severe traumatic brain injury, the use of aggressive versus conservative management remains controversial. The aim of this study was to assess the outcome of surgical alternatives for treatment of severe traumatic intracranial hematoma in patients ≥65 years old and identify factors that may contribute to the outcome. This retrospective study included 112 patients with traumatic intracranial hematoma. Logistic regression analysis was used to identify independent predictors of unfavorable outcome. The Glasgow Outcome Scale was used to evaluate the outcome. Surgery was performed in 70 (62.5%) patients ≥65 years old. A favorable outcome occurred in 33 (47.1%) surgical patients, and 23 (32.9%) surgical patients died. Patients who underwent surgery were less likely to have an unfavorable outcome (52.9% vs. 95.2%) and less likely to die (32.9% vs. 88.1%) at 6 months postinjury compared with patients treated conservatively. Multivariate logistic regression analysis revealed that lower Glasgow Coma Scale score (≤5) was a significant factor associated with unfavorable outcome (odds ratio [OR]= 18.7, 95% confidence interval [CI]= 5.2-95.5, P < 0.001) and mortality (OR= 10.7, 95% CI= 4.4-28.5, P < 0.001). However, neurosurgical intervention was a significant factor to negatively predict unfavorable outcome (OR= 0.03, 95% CI= 0.01-0.1, P < 0.001) and mortality (OR= 0.04, 95% CI= 0.01-0.1, P < 0.001). This study showed that Glasgow Coma Scale score (≤5) was a major determinant of outcome in elderly patients with severe traumatic brain injury. However, surgical treatment reduced mortality and improved outcome in the elderly patients in this study.

Elevated levels of cerebrospinal fluid S100B are associated with brain injury and unfavorable outcomes in children with central nervous system infections

Purpose: This work aimed to assess whether elevated levels of cerebrospinal fluid (CSF) S100B are associated with brain injury and unfavorable outcomes at discharge in children with central nervous system (CNS) infections. Methods: CSF S100B and associated clinical parameters were retrospectively analyzed in 83 children with CNS infections and 88 children without neurological pathology served as controls. Children with CNS infections were divided into an infectious encephalitis group and an infectious meningitis group based on whether cerebral parenchyma was involved, and CSF S100B levels in different age subgroups between the two groups were compared. The predictive value of CSF S100B in children with infectious encephalitis was evaluated by multivariate logistic regression analysis, and the discriminative power was investigated by receiver operating characteristic (ROC) analysis. Results: CSF S100B levels in the infectious encephalitis group were significantly higher than the infectious meningitis and the control group at each age range. CSF S100B ≥ 0.96 μg/L had 62.9% sensitivity and 76.2% specificity for diagnosing cerebral parenchyma injury in children with CNS infections. Increased CSF S100B levels were proven to be an independent predictor of unfavorable outcomes in children with infectious encephalitis and the optimal cut-off value (1.77 μg/L of CSF S100B) for predicting unfavorable outcomes in children with infectious encephalitis showed 61.1% sensitivity and 96.2% specificity. Conclusions: This study has demonstrated that elevated levels of CSF S100B are associated with brain injury and could be used as an independent predictor of clinically unfavorable outcomes at discharge in children with CNS infections.

Endovascular treatment of unruptured posterior circulation intracranial aneurysms.

Background and Purpose:Endovascular treatment of unruptured posterior circulation intracranial aneurysms (UPCIAs) is limited in the International Study of Unruptured Intracranial Aneurysms (ISUIA). The aim of this study is to evaluate the periprocedural morbidity, mortality, and midterm clinical and angiographic follow-ups of endovascular treatment of UPCIAs.Materials and Methods:Retrospective analysis of all patients treated in a 2-year period (89 patients: 10–78 years of age, mean: 45.5 ± 14.3/92 UPCIAs). Fifty-eight aneurysms were found incidentally, 12 in association with mass effect symptoms and 22 with stroke.Results:A clinical improvement or stable outcome was achieved in 84 patients (94.4%). The two cases of permanent morbidity included a patient with paralysis and another patient with hemianopia. One patient died after treatment of a giant fusiform vertebrobasilar aneurysm. In one patient, the aneurysm ruptured during treatment, resulting in death. Another patient suffered a fatal aneurysm rupture 4 days after treatment. Giant size (P = 0.005) and mass effect presentation (P = 0.029) were independent predictors of unfavorable outcomes in UPCIAs. Angiographic follow-up was available in 76 of the 86 surviving patients (88.4%) with a mean of 6.8 months (range: 1–36 months). Recanalization in six patients (7.9%) at 3 months, 4 months, 4 months, 24 months, and 36 months required retreatment in three patients. In-stent stenosis of >50% was found in three patients.Conclusion:Endovascular therapy is an attractive option for UPCIAs with stable midterm outcome. However, the current endovascular option seems to have a limitation for the treatment of the aneurysm with giant size or mass effect presentation.

The relationship between the duration of obstructive respiratory events and outcomes of multilevel upper airway surgery in patients with obstructive sleep apnea.

We aimed to examine whether the duration of respiratory events and related oximetric values are associated with outcomes of multilevel upper airway surgery in patients with moderate-severe obstructive sleep apnea (OSA). The records of patients with a preoperative apnea-hypopnea index (AHI) >15events/h, who underwent uvulopharyngopalatoplasty plus tongue base suspension with or without septoplasty between 2012 and 2014, were reviewed retrospectively. If the postoperative 6th month AHI was <20events/h with at least a 50% reduction from preoperative rates, the outcome of surgery was regarded as successful, otherwise, as failure. To calculate factors predictive of surgical outcomes, a receiver operating characteristic (ROC) analysis was performed. Logistic regression analyses were utilized to obtain the Odds ratio (OR) and 95% confidential interval (CI). In total, 82 patients were enrolled in the study. Sixty-one patients (74.4%) met the success criteria. The mean obstructive apnea duration (OAD) was the sole variable with a significant and satisfactory area under the curve (AUC) value [AUC (95% CI)=0.719 (0.597-0.842), p=0.003]. The cutoff value was found to be 26.75s with 71.4% sensitivity, 72.1% specificity, 88.0% positive predictive value, and 46.9% negative predictive value. Univariate analysis revealed an association between surgical failure and mean OAD>26.75s, total apnea duration, lowest SaO2, mean SaO2, mean O2 desaturation, and oxygen desaturation index, although only mean OAD>26.75s remained to be an independent predictor for unfavorable outcome after adjustment for other confounders in multivariate analysis [OR (95% CI)=3.92 (1.08-14.17), p=0.041]. The current study suggests that OSA patients having longer OAD are in the risk of having surgical failure.

Younger Stroke Patients With Large Pretreatment Diffusion-Weighted Imaging Lesions May Benefit From Endovascular Treatment.

Lesion volume on diffusion-weighted magnetic resonance imaging (DWI) before acute stroke therapy is a predictor of outcome. Therefore, patients with large volumes are often excluded from therapy. The aim of this study was to analyze the impact of endovascular treatment in patients with large DWI lesion volumes (>70 mL). Three hundred seventy-two patients with middle cerebral or internal carotid artery occlusions examined with magnetic resonance imaging before treatment since 2004 were included. Baseline data and 3 months outcome were recorded prospectively. DWI lesion volumes were measured semiautomatically. One hundred five patients had lesions >70 mL. Overall, the volume of DWI lesions was an independent predictor of unfavorable outcome, survival, and symptomatic intracerebral hemorrhage (P<0.001 each). In patients with DWI lesions >70 mL, 11 of 31 (35.5%) reached favorable outcome (modified Rankin scale score, 0-2) after thrombolysis in cerebral infarction 2b-3 reperfusion in contrast to 3 of 35 (8.6%) after thrombolysis in cerebral infarction 0-2a reperfusion (P=0.014). Reperfusion success, patient age, and DWI lesion volume were independent predictors of outcome in patients with DWI lesions >70 mL. Thirteen of 66 (19.7%) patients with lesions >70 mL had symptomatic intracerebral hemorrhage with a trend for reduced risk with avoidance of thrombolytic agents. There was a growing risk for poor outcome and symptomatic intracerebral hemorrhage with increasing pretreatment DWI lesion volumes. Nevertheless, favorable outcome was achieved in every third patient with DWI lesions >70 mL after successful endovascular reperfusion, whereas after poor or failed reperfusion, outcome was favorable in only every 12th patient. Therefore, endovascular treatment might be considered in patients with large DWI lesions, especially in younger patients.

Abstract 4906: TP53 mutations are mutually exclusive with FLT3 and NPM mutations in AML patients and are strongly associated with complex karyotype and poor outcome

Abstract AML is a heterogeneous disease with a variety of structural and numerical chromosomal and genetic alterations that provided important prognostic information capable to guide therapy and predict outcome. The reported TP53 mutation rate in AML is low (2.1%). By contrast, the incidence of FLT3 disruption is frequent (20-30%) and is an independent predictor of unfavourable outcome of acquired clinical resistance to FLT3 inhibitors. TP53 mutations in AML with a complex karyotype (CK) is higher (69-78%), but few data are available for association between the most common AML associated lesions such as FLT3, NPM1, DNMT3A, IDH2 and TP53 mutation or CK. Aims: To investigate the frequency, the types of mutations, the associated cytogenetic, the molecular abnormalities, the correlation with known molecular alterations (FLT3, NPM, etc.) and the prognostic role TP53 mutations in adult AML pts. Patients and Methods: 886 AML patients were analysed for cytogenetic and for a panel of genetic alterations (FLT3, NPM, WT1, DNMT3A, IDH1-2 etc). Of these, 200 adult AML pts were also examined for TP53 mutations using several methods, including Sanger sequencing, NGS and HiSeq 2000 platform (38/200) and were correlated with cytogenetic analysis. Results: 55 pts (27.5%) showed 3 or more chromosome abnormalities (CK-AML), 83 (41.5%) presented one or two cytogenetic abnormalities (other-AML) and 43 pts (21.5%) have normal karyotype (nK). In 19 cases the karyotype was not available. Sanger sequencing analysis detected TP53 mutations on 29 patients with 36 different types of mutations (32 deleterious point mutations; 4 deletions); seven pts (4%) have 2 mutations. Mostly (23/29) of the TP53 mutated pts (79.3%) had CK while only 6/29 (21%) mutated pts have “no CK”. Overall, between pts with CK, TP53 frequency is 41.8% (P&amp;gt;0,0001). 120 pts were analysed for concomitant presence of TP53 mutations and FLT3/NPM1 disruption/mutation: revealing a significant relation between pts with FLT3-ITD or NPM1 and TP53 wild-type (p = 0.043 and 0.022 respectively). As for clinical outcome alterations of TP53 were significantly associated with poor outcome (OS and EFS p&amp;lt;0.0001). The very worsened outcome of TP53 mutations overcome the negative prognostic role of FLT3 mutations (P0.0001). WES analysis done in 38 pts (33 TP53 wt and 5 pts TP53 mutated) revealed no genes exclusively mutated in the 5 TP53 mutated pts. Conclusions: Our data demonstrated that TP53 mutations occur in 14.5% of AML with a higher frequency in the subgroup of CK-AML (p&amp;lt;0.0001) and are mutually exclusive with FLT3 and/or NPM1; they predicted to be deleterious and significantly correlated with worse prognosis and may confer resistance to conventional and innovative therapy. For these reasons, TP53 mutation screening should be recommended at least in CK-AML pts. ELN, AIL, AIRC, PRIN, 2010-12 L. Bolondi, FP7 NGS-PTL project. Citation Format: Anna Ferrari, Cristina Papayannidis, Elisa Zuffa, Carmen Baldazzi, Antonella Padella, Eugenia Franchini, Ilaria Iacobucci, Stefania Paolini, Viviana Guadagnuolo, Margherita Perricone, Valentina Robustelli, Claudia Venturi, Maria Chiara Abbenante, Sarah Parisi, Chiara Sartor, Francesca Volpato, Federica Cattina, Giorgia Simonetti, Maria Chiara Fontana, Maria Teresa Bochicchio, Federica Frabetti, Elisa Lani, Katia Mancuso, Beatrice Zannetti, Simona Luatti, Emanuela Ottaviani, Nicoletta Testoni, Giovanni Martinelli. TP53 mutations are mutually exclusive with FLT3 and NPM mutations in AML patients and are strongly associated with complex karyotype and poor outcome. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4906. doi:10.1158/1538-7445.AM2015-4906