Relationship between imaging biomarkers, age, progression and symptom severity in Alzheimer's disease.

The early diagnostic value of glucose hypometabolism and atrophy as potential neuroimaging biomarkers of mild cognitive impairment (MCI) and Alzheimer's disease (AD) have been extensively explored using [18F]fluorodeoxyglucose positron emission tomography (FDG-PET) and structural magnetic resonance imaging (MRI). The vast majority of previous imaging studies neglected the effects of single factors, such as age, symptom severity or time to conversion in MCI thus limiting generalisability of results across studies. Here, we investigated the impact of these factors on metabolic and structural differences. FDG-PET and MRI data from AD patients (n = 80), MCI converters (n = 65) and MCI non-converters (n = 64) were compared to data of healthy subjects (n = 79). All patient groups were split into subgroups by age, time to conversion (for MCI), or symptom severity and compared to the control group. AD patients showed a strongly age-dependent pattern, with younger patients showing significantly more extensive reductions in gray matter volume and glucose utilisation. In the MCI converter group, the amount of glucose utilisation reduction was linked to the time to conversion but not to atrophy. Our findings indicate that FDG-PET might be more closely linked to future cognitive decline whilst MRI being more closely related to the current cognitive state reflects potentially irreversible damage.

Exploring the proposed DSM-5 diagnostic threshold and severity scale for the alcohol use disorder

Aims :¦Several studies have questioned the validity of separating the diagnosis of alcohol abuse from that of alcohol dependence, and the DSM-5 task force has proposed combining the criteria from these two diagnoses to assess a single category of alcohol use disorders (AUD). Furthermore, the DSM-5 task force has proposed including a new 2-symptom threshold and a severity scale based on symptom counts for the AUD diagnosis. The current study aimed to examine these modifications in a large population-based sample.¦Method :¦Data stemmed from an adult sample (N=2588 ; mean age 51.3 years (s.d.: 0.2), 44.9% female) of current and lifetime drinkers from the PsyCoLaus study, conducted in the Lausanne area in Switzerland. AUDs and validating variables were assessed using a semi-structured diagnostic interview for the assessment of alcohol¦and other major psychiatric disorders. First, the adequacy of the proposed 2- symptom threshold was tested by comparing threshold models at each possible cutoff and a linear model, in relation to different validating variables. The model with the smallest Akaike Criterion Information (AIC) value was established as the best¦model for each validating variable. Second, models with varying subsets of individual AUD symptoms were created to assess the associations between each symptom and the validating variables. The subset of symptoms with the smallest AIC value was established as the best subset for each validator.¦Results :¦1) For the majority of validating variables, the linear model was found to be the best fitting model. 2) Among the various subsets of symptoms, the symptoms most frequently associated with the validating variables were : a) drinking despite having knowledge of a physical or psychological problem, b) having had a persistent desire or unsuccessful efforts to cut down or control drinking and c) craving. The¦least frequent symptoms were : d) drinking in larger amounts or over a longer period than was intended, e) spending a great deal of time in obtaining, using or recovering from alcohol use and f) failing to fulfill major role obligations.¦Conclusions :¦The proposed DSM-5 2-symptom threshold did not receive support in our data. Instead, a linear AUD diagnosis was supported with individuals receiving an increasingly severe AUD diagnosis. Moreover, certain symptoms were more frequently associated with the validating variables, which suggests that these¦symptoms should be considered as more severe.

Status Epilepticus Severity Score (STESS): a tool to orient early treatment strategy

BACKGROUND : Status epilepticus (SE) treatment ranges from small benzodiazepine doses to coma induction. For some SE subgroups, it is unclear how the risk of an aggressive therapeutic approach balances with outcome improvement. We recently developed a prognostic score (Status Epilepticus Severity Score, STESS), relying on four outcome predictors (age, history of seizures, seizure type and extent of consciousness impairment), determined before treatment institution. Our aim was to assess whether the score might have a role in the treatment strategy choice. METHODS : This cohort study involved adult patients in three centers. For each patient, the STESS was calculated before primary outcome assessment: survival vs. death at discharge. Its ability to predict survival was estimated through the negative predictive value for mortality (NPV). Stratified odds ratios (OR) for mortality were calculated considering coma induction as exposure; strata were defined by the STESS level. RESULTS : In the observed 154 patients, the STESS had an excellent negative predictive value (0.97). A favorable STESS was highly related to survival (P < 0.001), and to return to baseline clinical condition in survivors (P < 0.001). The combined Mantel-Haenszel OR for mortality in patients stratified after coma induction and their STESS was 1.5 (95 % CI: 0.59-3.83). CONCLUSION : The STESS reliably identifies SE patients who will survive. Early aggressive treatment could not be routinely warranted in patients with a favorable STESS, who will almost certainly survive their SE episode. A randomized trial using this score would be needed to confirm this hypothesis.

Association of biomarkers of lipid modification with functional and morphological indices of coronary stenosis severity in stable coronary artery disease.

Biomarkers of blood lipid modification and oxidative stress have been associated with increased cardiovascular morbidity. We sought to determine whether these biomarkers were related to functional indices of stenosis severity among patients with stable coronary artery disease. We studied 197 consecutive patients with stable coronary artery disease due to single vessel disease. Fractional flow reserve (FFR) ≤ 0.80 was assessed as index of a functionally significant lesion. Serum levels of secretory phospholipase A2 (sPLA2) activity, secretory phospholipase A2 type IIA (sPLA2-IIA), myeloperoxydase (MPO), lipoprotein-associated phospholipase A2 (Lp-PLA2), and oxidized low-density lipoprotein (OxLDL) were assessed using commercially available assays. Patients with FFR > 0.8 had higher sPLA2 activity, sPLA2 IIA, and OxLDL levels than patients with FFR ≤ 0.8 (21.25 [16.03-27.28] vs 25.85 [20.58-34.63] U/mL, p < 0.001, 2.0 [1.5-3.4] vs 2.6 [2.0-3.4] ng/mL, p < 0.01; and 53.0 [36.0-71.0] vs 64.5 [50-89.25], p < 0.001 respectively). Patients with FFR > 0.80 had similar Lp-PLA2 and MPO levels versus those with FFR ≤ 0.8. sPLA2 activity, sPLA2 IIA significantly increased area under the curve over baseline characteristics to predict FFR ≤ 0.8 (0.67 to 0.77 (95 % confidence interval [CI]: 0.69-0.85) p < 0.01 and 0.67 to 0.77 (95 % CI: 0.69-0.84) p < 0.01, respectively). Serum sPLA2 activity as well as sPLA2-IIA level is related to functional characteristics of coronary stenoses in patients with stable coronary artery disease.

Social factors related to the clinical severity of influenza cases in Spain during the A(H1N1)2009 virus pandemic

Background During the 2009 influenza pandemic, a change in the type of patients most often affected by influenza was observed. The objective of this study was to assess the role of individual and social determinants in hospitalizations due to influenza A (H1N1) 2009 infection. Methods We studied hospitalized patients (cases) and outpatients (controls) with confirmed influenza A (H1N1) 2009 infection. A standardized questionnaire was used to collect data. Variables that might be related to the hospitalization of influenza cases were compared by estimation of the odds ratio (OR) and 95% confidence intervals (CI) and the variables entered into binomial logistic regression models. Results Hospitalization due to pandemic A (H1N1) 2009 influenza virus infections was associated with non-Caucasian ethnicity (OR: 2.18, 95% CI 1.17 − 4.08), overcrowding (OR: 2.84, 95% CI 1.20 − 6.72), comorbidity and the lack of previous preventive information (OR: 2.69, 95% CI: 1.50 − 4.83). Secondary or higher education was associated with a lower risk of hospitalization (OR 0.56, 95% CI: 0.36 − 0.87) Conclusions In addition to individual factors such as comorbidity, other factors such as educational level, ethnicity or overcrowding were associated with hospitalization due to A (H1N1) 2009 influenza virus infections.

Prediction of hemodynamic severity of coarctation by magnetic resonance imaging.

A published formula containing minimal aortic cross-sectional area and the flow deceleration pattern in the descending aorta obtained by cardiovascular magnetic resonance predicts significant coarctation of the aorta (CoA). However, the existing formula is complicated to use in clinical practice and has not been externally validated. Consequently, its clinical utility has been limited. The aim of this study was to derive a simple and clinically practical algorithm to predict severe CoA from data obtained by cardiovascular magnetic resonance. Seventy-nine consecutive patients who underwent cardiovascular magnetic resonance and cardiac catheterization for the evaluation of native or recurrent CoA at Children's Hospital Boston (n = 30) and the University of California, San Francisco (n = 49), were retrospectively reviewed. The published formula derived from data obtained at Children's Hospital Boston was first validated from data obtained at the University of California, San Francisco. Next, pooled data from the 2 institutions were analyzed, and a refined model was created using logistic regression methods. Finally, recursive partitioning was used to develop a clinically practical prediction tree to predict transcatheter systolic pressure gradient ≥ 20 mm Hg. Severe CoA was present in 48 patients (61%). Indexed minimal aortic cross-sectional area and heart rate-corrected flow deceleration time in the descending aorta were independent predictors of CoA gradient ≥ 20 mm Hg (p <0.01 for both). A prediction tree combining these variables reached a sensitivity and specificity of 90% and 76%, respectively. In conclusion, the presented prediction tree on the basis of cutoff values is easy to use and may help guide the management of patients investigated for CoA.

Disease-associated mutations in the actin-binding domain of filamin B cause cytoplasmic focal accumulations correlating with disease severity.

Dominant missense mutations in FLNB, encoding the actin-cross linking protein filamin B (FLNB), cause a broad range of skeletal dysplasias with varying severity by an unknown mechanism. Here these FLNB mutations are shown to cluster in exons encoding the actin-binding domain (ABD) and filamin repeats surrounding the flexible hinge 1 region of the FLNB rod domain. Despite being positioned in domains that bind actin, it is unknown if these mutations perturb cytoskeletal structure. Expression of several full-length FLNB constructs containing ABD mutations resulted in the appearance of actin-containing cytoplasmic focal accumulations of the substituted protein to a degree that was correlated with the severity of the associated phenotypes. In contrast, study of mutations leading to substitutions in the FLNB rod domain that result in the same phenotypes as ABD mutations demonstrated that with only one exception disease-associated substitutions, surrounding hinge 1 demonstrated no tendency to form actin-filamin foci. The exception, a substitution in filamin repeat 6, lies within a region previously implicated in filamin-actin binding. These data are consistent with mutations in the ABD conferring enhanced actin-binding activity but suggest that substitutions affecting repeats near the flexible hinge region of FLNB precipitate the same phenotypes through a different mechanism.

Qualitative grading of severity of lumbar spinal stenosis based on the morphology of the dural sac on magnetic resonance images.

STUDY DESIGN.: Retrospective radiologic study on a prospective patient cohort. OBJECTIVE.: To devise a qualitative grading of lumbar spinal stenosis (LSS), study its reliability and clinical relevance. SUMMARY OF BACKGROUND DATA.: Radiologic stenosis is assessed commonly by measuring dural sac cross-sectional area (DSCA). Great variation is observed though in surfaces recorded between symptomatic and asymptomatic individuals. METHODS.: We describe a 7-grade classification based on the morphology of the dural sac as observed on T2 axial magnetic resonance images based on the rootlet/cerebrospinal fluid ratio. Grades A and B show cerebrospinal fluid presence while grades C and D show none at all. The grading was applied to magnetic resonance images of 95 subjects divided in 3 groups as follows: 37 symptomatic LSS surgically treated patients; 31 symptomatic LSS conservatively treated patients (average follow-up, 2.5 and 3.1 years); and 27 low back pain (LBP) sufferers. DSCA was also digitally measured. We studied intra- and interobserver reliability, distribution of grades, relation between morphologic grading and DSCA, as well relation between grades, DSCA, and Oswestry Disability Index. RESULTS.: Average intra- and interobserver agreement was substantial and moderate, respectively (k = 0.65 and 0.44), whereas they were substantial for physicians working in the study originating unit. Surgical patients had the smallest DSCA. A larger proportion of C and D grades was observed in the surgical group. Surface measurementsresulted in overdiagnosis of stenosis in 35 patients and under diagnosis in 12. No relation could be found between stenosis grade or DSCA and baseline Oswestry Disability Index or surgical result. C and D grade patients were more likely to fail conservative treatment, whereas grades A and B were less likely to warrant surgery. CONCLUSION.: The grading defines stenosis in different subjects than surface measurements alone. Since it mainly considers impingement of neural tissue it might be a more appropriate clinical and research tool as well as carrying a prognostic value.

The interrater reliability of the pulmonary embolism severity index

RésuméLe PESI (Pulmonary Embolism Severity Index) est un score clinique pronostique s'appliquant à des patients présentant un diagnostic d'embolie pulmonaire. Notre objectif était de démontrer la reproductibilité de ce score entre différents médecins chez des patients présentant une embolie pulmonaire. Nous avons donc identifié, de façon prospective, des patients présentant une embolie pulmonaire nouvellement diagnostiquée aux urgences d'un Hôpital Universitaire (CHUV, Lausanne). Pour tous ces patients, le médecin assistant en charge ainsi que le chef de clinique superviseur ont individuellement collecté les différentes variables permettant d'établir le score selon le PESI. Ils ont, ensuite, de façon indépendante, classifié les patients dans 5 classes de risque (1-V) ainsi qu'en deux groupes à bas risque versus haut risque, respectivement les classes i-ll et les classes III à V.Nous avons examiné la reproductibilité des données entre deux groupes de médecins (médecins assistants vs chefs de clinique), pour chacune des variables constituant le PESI, pour le score total en points, pour l'attribution aux 5 classes de risque ainsi que pour la classification en deux groupes à haut risque versus bas risque. Cette évaluation de la reproductibilité des résultats obtenus par les différents médecins s'est basée sur le calcul du Kappa (K) ainsi sur les Coefficients de Corrélation Intra-classe (ICC).Parmi les 48 patients présentant une Embolie Pulmonaire inclus dans notre étude, les coefficients de reproductibilité entre médecins assistants et chefs de clinique étaient supérieurs à 0.60 pour 10 des 11 variables du PESI. La reproductibilité entre les 2 groupes de médecins, pour le total des points, pour l'attribution à une classe de risque I à V, ainsi que pour la classification en bas versus haut risque était presque parfaite.Nos résultats démontrent la haute reproductibilité du PESI, et appuient donc l'intérêt de son utilisation pour la stratification du risque chez des patients présentant une embolie pulmonaire.

Plant growth and leaf-spot severity on eucalypt at different CO2concentrations in the air

The objective of this work was to evaluate the effects of increased air-CO2 concentration on plant growth and on leaf-spot caused by Cylindrocladium candelabrumin Eucalyptus urophylla. Seedlings were cultivated for 30 days at 451, 645, 904, and 1,147 µmol mol-1 CO2 ; then, they were inoculated with the pathogen and kept under the same conditions for seven days. Increased CO2concentration increased plant height and shoot dry matter mass, and decreased disease incidence and severity. Stem diameter was not affected by the treatments. Increased concentrations of atmospheric CO2 favorably affect eucalypt growth and reduce leaf-spot severity.

Pulmonary embolism severity index and troponin testing for the selection of low-risk patients with acute symptomatic pulmonary embolism.

Summary Background: The combination of the Pulmonary Embolism Severity Index (PESI) and troponin testing could help physicians identify appropriate patients with acute pulmonary embolism (PE) for early hospital discharge. Methods: This prospective cohort study included a total of 567 patients from a single center registry with objectively confirmed acute symptomatic PE. On the basis of the PESI, each patient was classified into 1 of 5 classes (I to V). At the time of hospital admission, patients had troponin I (cTnI) levels measured. The endpoint of the study was all-cause mortality within 30 days after diagnosis. We calculated the mortality rates in 4 patient groups: group 1: PESI class I-II plus cTnI <0.1 ng mL(-1); group 2: PESI classes III-V plus cTnI <0.1 ng mL(-1); group 3: PESI classes I-II plus cTnI >/= 0.1 ng mL(-1); and group 4: PESI classes III-V plus cTnI >/= 0.1 ng mL(-1). Results: The study cohort had a 30-day mortality of 10% (95% confidence interval [CI], 7.6 to 12.5%). Mortality rates in the 4 groups were 1.3%, 14.2%, 0% and 15.4%, respectively. Compared to non-elevated cTnl, the low-risk PESI had a higher negative predictive value (NPV) (98.9% vs 90.8%) and negative likelihood ratio (NLR) (0.1 vs 0.9) for predicting mortality. The addition of non-elevated cTnI to low-risk PESI did not improve the NPV or the NLR compared to either test alone. Conclusions: Compared to cTnl testing, PESI classification more accurately identified patients with PE who are at low risk of all-cause death within 30-days of presentation.