Clinical Severity Index Research Articles

Giardia duodenalis infection in dogs affected by primary chronic enteropathy.

Background:Canine primary chronic enteropathy (CE) includes a heterogeneous group of diseases characterized by chronic gastrointestinal signs.Aim:This study evaluated the occurrence of Giardia duodenalis infection in primary CE-affected dogs.Methods:Forty-seven CE-affected dogs of different age and sex were enrolled in the study. For each dog, frequency of defecation, fecal consistency, and eventual fecal abnormalities were evaluated. A clinical scoring index of CE severity (clinical chronic enteropathy activity index) was also assessed, and the type of enteropathy was retrospectively classified. For parasitological analysis, fresh fecal samples collected from each dog were examined by fresh and Lugol stained smears, flotation test, and a rapid immunoassay. Giardia duodenalis genotypes were identified by molecular analysis. Differences of clinical parameters between G. duodenalis positive and G. duodenalis negative dogs were statistically evaluated.Results:Among the CE canine patients, 16 out of 47 (34%) dogs were found positive for G. duodenalis and assemblages C and D were identified. No statistical differences emerged according to the types of CE between G. duodenalis-positive and G. duodenalis-negative dog groups. The clinical index of CE severity was indicative of significant less severe clinical forms in G. duodenalis-positive dogs (p = 0.037).Conclusion:Results here obtained shows how G. duodenalis may be present in primary CE-affected dogs and further investigations are needed to clarify the real significance of mild clinical presentation in G. duodenalis-positive dogs affected by CE.

Factors associated with residual pulmonary thromboembolism detected by computed tomography pulmonary angiography

BACKGROUND: Complete resolution of pulmonary vascular obstruction is not totally achieved in patients with acute pulmonary thromboembolism (PE). In this study, we tried to identify the factors associated with residual PE.MATERIALS AND METHODS: Patients with a diagnosis of acute PE from two centers were retrospectively analyzed. Residual PE was detected by computed tomography (CT) pulmonary angiography. Investigated parameters were unprovoked PE, clinical severity index (pulmonary embolism severity index score), D-dimer, troponin I, central pulmonary embolism, clot burden (Qanadli score), CT indexes of right ventricle (RV) overload (RV/left ventricle and pulmonary artery/aorta), massive PE, coexisting deep venous thrombosis signs and symptoms, and follow-up CT time.RESULTS: On univariate analysis, follow-up CT time and clot burden at the time of diagnosis were significantly associated with residual PE (P = 0.02 and P = 0.002, respectively). Initial D-dimer levels were higher in patients with residual PE although statistical significance was not reached (P = 0.08). On multivariate analysis, clot burden and follow-up CT time remained significant (hazard ratio [95% confidence interval] of 4.31 [1.31–14.12] and 2.47 [0.92–6.62], respectively).CONCLUSION: Our results suggest that higher clot burden may be an independent predictor for residual PE along with the timing of follow-up CT.

Fecal MicroRNAs Show Promise as Noninvasive Crohn's Disease Biomarkers.

BackgroundShort non-coding microRNAs (miRNAs) are involved in various cellular processes during disease progression of Crohn’s disease (CD) and remarkably stable in feces, which make them attractive biomarker candidates for reflecting intestinal inflammatory processes. Here we investigated the potential of fecal miRNAs as noninvasive and translational CD biomarkers.MethodsMiRNAs were screened in feces of 52 patients with CD and 15 healthy controls using RNA sequencing and the results were confirmed by PCR. The relationship between fecal miRNA levels and the clinical CD activity index (CDAI) or CD endoscopic index of severity (CDEIS) was explored, respectively. Additionally, fecal miRNAs were investigated in dextran sodium sulfate, adoptive T-cell transfer, and Helicobacter typhlonius/stress-induced murine colitis models using the NanoString platform.ResultsNine miRNAs (miR-15a-5p, miR-16-5p, miR-128-3p, miR-142-5p, miR-24-3p, miR-27a-3p, miR-223-3p, miR-223-5p, and miR-3074-5p) were significantly (adj. P < 0.05, >3-fold) increased whereas 8 miRNAs (miR-10a-5p, miR-10b-5p, miR-141-3p, miR-192-5p, miR-200a-3p, miR-375, miR-378a-3p, and let-7g-5p) were significantly decreased in CD. MiR-192-5p, miR-375, and miR-141-3p correlated (P < 0.05) with both CDAI and CDEIS whereas miR-15a-5p correlated only with CDEIS. Deregulated expression of miR-223-3p, miR-16-5p, miR-15a-5p, miR-24-3p, and miR-200a-3p was also observed in murine models. The identified altered fecal miRNA levels reflect pathophysiological mechanisms in CD, such as Th1 and Th17 inflammation, autophagy, and fibrotic processes.ConclusionsOur translational study assessed global fecal miRNA changes of patients with CD and relevant preclinical models. These fecal miRNAs show promise as translational and clinically useful noninvasive biomarkers for mechanistic investigation of intestinal pathophysiology, including monitoring of disease progression.

Validity of the Cushing's Syndrome Severity Index in Patients with Iatrogenic Cushing's Syndrome.

Currently there are no clinimetric instruments for the measurement of the severity of iatrogenic Cushing's syndrome (ICS). Sonino et al. created a clinical severity index of endogenous Cushing's disease (CSI) but it has not been applied to patients with ICS. To validate and determine the utility of the CSI and its correlation with clinical variables in rheumatological patients with continuous use of glucocorticoids (GC). Patients with a history of continuous systemic GC use (for at least 4 weeks) indicated for treatment of rheumatological disease were included. All the patients filled out a questionnaire on sociodemographic data, characteristics of the CG used; the way of use and the presence or absence of adverse events. The CSI was applied by 2 observers independently. Consistency, interobserver concordance and principal component analysis were calculated. A total of 32 patients with an average age of 35.72±12.8 years were studied; 29 were women (90.6%). The average CSI score by the first observer was 3.50±2.02, and by the second observer was 2.31±1.75 (p=.004). The interobserver concordance was low in the items with imprecise definitions; for which modifications were made in the definitions to improve their performance. The CSI scores correlated with the presence of adverse effects and the type of dose used. The CSI has an adequate correlation with clinical manifestations in patients with chronic use of GC. The clinimetric characteristics of the questionnaire improved by standardising the definitions of subjective clinical variables.

Prognostic markers and assessment of a previously published clinical severity index in 109 hospitalised dogs with acute presentation of pancreatitis

BackgroundAcute pancreatitis (AP) is common in dogs. Nevertheless, validated clinical severity index (CSI) scoring systems to assess severity and guide treatment in current, large-scale studies are unavailable.MethodsThis is a retrospective...

2321. FluMex: A New Clinical Severity Index in Mexican Hospitalized Patients with Influenza

BackgroundInfluenza virus infection is frequently characterized by a complex clinical behavior and outcomes can be fatal. There are many published scoring methods aimed for pulmonary infections and sepsis severity nevertheless they lack adequate sensitivity and specificity in patients with Influenza.MethodsFrom 2013 to 2018, hospitalized patients from five hospitals from the Christus Muguerza health group from Monterrey, Mexico who had a positive rapid influenza-test and/or positive PCR for Influenza virus were enrolled. Risk factors for severity and mortality were evaluated calculating odds ratio with a binary logistic regression model and were adjusted for other factors. The new index was then compared with pneumonia severity scores by assessing area under the curve(AUC), sensitivity and specificity.ResultsWe analyzed data from 125 patients hospitalized with confirmed Influenza infection. Less than 1% had received the corresponding seasonal influenza vaccine. Type 2 diabetes (T2D) and hypertension (HT) were the most prevalent comorbidities. Odds ratios were significant for age > 65 years, body mass index (BMI) > 30, T2D, HT, pulsoximetry < 90%, respiratory rate > 22 per minute, altered mental status, blood urea nitrogen (BUN) > 19 mg/dL, elevated lactate dehydrogenase (LDH), and an abnormal chest X-ray. The FluMex score was applied to a control group of 125 admitted patients with confirmed Influenza infection. AUC was 0.63 (CI 95%, 0.52–0.74; P < 0.05) for severity and 0.90 (IC 95%, 0.83–0.97; P < 0.05) for mortality, showing better predictive performance than other pneumonia and sepsis scores such as CURB-65, PSI, CROMI, SIRS, SOFA, qSOFA and ILI (Table 1).ConclusionThe FluMex scoring system can be a useful tool for patients with suspected Influenza infection in predicting severity and mortality, helping to improve care and resource management. Disclosures All authors: No reported disclosures.

The Influence of Ketogenic Diets on Psoriasiform-Like Skin Inflammation

The Influence of Ketogenic Diets on Psoriasiform-Like Skin Inflammation

Comparison of the effect of photodynamic therapy and topical corticosteroid on oral lichen planus lesions.

In this study, the effect of photodynamic therapy with topical corticosteroid in oral lichen planus patients was compared. In this randomized, double-blind clinical trial, eight patients with bilateral oral OLP lesions were recruited. Toluidine blue was applied on the lesions of both sides; a 660-nm diode laser InGaAlP was irradiated for 10min (power: 25mW, fluence: 19.23J/cm2 , probe cross section: 0.78cm2 ) for three sessions. In the control side of the oral mucosa, only sham laser was used. Follow-up sessions were held on weeks 3 and 7. In week 3, oral paste triamcinolone acetonide 0.1% was prescribed. Response rates were assessed clinically by VAS, Thongprasom sign scoring, clinical severity index, efficacy indices, and the amount of reduction in the size of the lesions. The Mann-Whitney test was used to evaluate the treatment outcomes. In spite of the control side, all scores improved significantly between sessions 0 and 4 for the intervention side. The differences between the changes in almost all scores between sessions 0 and 4 in both the intervention and control sides were significantly considerable (p value<.05). Photodynamic therapy can be used as an alternative therapy alongside standard methods or as a new modality for refractory OLP.

Symptom presence versus symptom intensity in understanding the severity of depression: Implications for documentation in electronic medical records

BackgroundData mining efforts have been applied to research data bases to develop statistical models for predicting outcomes. Electronic medical records have the potential to enable efforts to apply statistical techniques to mine large clinical data bases. Of course, such prediction algorithms will only be as good as the data that is available to input. The question that we address in the present report from the Rhode Island Methods to Improve Diagnostic Assessment and Services (MIDAS) project is how much information might be gained from dimensional ratings of symptom severity over and above that which is accounted for when determining symptom presence. Such results could have implications for how medical record documentation should be established. MethodsPatients were evaluated with a semi-structured interview, and the presence of each symptom of major depressive disorder (MDD) was recorded. Patients were also rated on the Clinical Global Index of Severity (CGI-S). ResultsA multiple regression analysis entering the presence of MDD symptoms as predictors of the CGI had a cumulative R2 of 0.26. A multiple regression analysis entering all symptom severity ratings as predictors of the CGI had a cumulative R2 of 0.40. LimitationsThe study was based on patients presenting for outpatient treatment to a single clinical practice. Symptoms that are not diagnostic criteria for MDD were not examined. DiscussionResearch institutions interested in using data mining statistical approaches of electronic medical records should consider having the clinicians rate whether symptoms are mild, moderate or severe and not just whether they are present or absent.

Impact of collateral flow on true FFR prediction for left main coronary stenoses with downstream lesions

The Fractional Flow Reserve (FFR) is a clinical index of functional severity validated for isolated stenoses. FFR may be viewed as the ratio of achievable blood flow in a stenotic artery to the the...

Midwives’ education and training in Complementary Alternative Medicine/Therapies: a national survey

Acute pancreatitis and acute kidney injury are well-documented comorbidities in human medicine. Dogs that develop acute kidney injury during hospitalization have significantly higher mortality rates than those that do not. The aim of this study was to evaluate the prevalence of acute kidney injury in dogs with acute pancreatitis and the prognostic value of various clinicopathological parameters. Cases of acute pancreatitis presented between January 2012 and June 2016 were identified. The diagnosis of acute pancreatitis was based on two or more of the following clinical signs: abdominal pain, diarrhea, vomiting or anorexia/hyporexia, no other abdominal extra-pancreatic diseases at abdominal ultrasound, and abnormal SNAP cPL test. Diagnosis of acute kidney injury was based on the guidelines of the International Renal Interest Society. Dogs were classified into survivors and non-survivors. Serum creatinine, urea, amylase, total calcium, total cholesterol, C-reactive protein, WBC and band neutrophils were evaluated at admission. Clinical severity index was calculated at admission. Clinical and clinicopathological data were compared between survivors and non-survivors.Sixty-five dogs with acute pancreatitis were assessed. Clinical severity index ≥ 6.5 were associated with poor outcome (P = 0.0011). Serum urea and creatinine concentrations at admission were significantly lower in survivors than non-survivors (P < 0.0001 and P = 0.0002, respectively). Acute kidney injury was diagnosed in 17/65 dogs (26.2%) and was associated with poor outcome (P < 0.0001). Oligo-anuria was associated with poor outcome (P = 0.0294). Increased clinical severity index and azotemia in dogs with acute pancreatitis were associated with an increased risk of mortality. Acute kidney injury may be a comorbidity of canine acute pancreatitis. The presence of oligo-anuria is associated with poor outcome.

Investigating the reliability of suicide attempt history reporting across five measures: A study of US military service members at risk of suicide.

Utilizing a sample of military service members at risk of suicide, this study aimed to: (a) identify patterns of suicide attempt (SA) history reporting across five measures and (b) evaluate whether consistent SA reporters (i.e., individuals who consistently report an SA history across measures) differ from inconsistent SA reporters on other clinical severity indices. Participants (N = 984) completed five validated SA history measures and self-report psychiatric symptom measures. Of the sample, 35.4% inconsistently responded to SA history measures. Inconsistent reporters disclosed more severe suicide threat histories than consistent reporters. On all other clinical severity indices, inconsistent reporters evinced either less severe or comparable symptom levels. A nontrivial portion of service members may respond inconsistently to different assessments of SA history. Research is needed to identify factors that account for inconsistent SA history reporting and to improve the accuracy of SA history assessments among military personnel.

Characterizing the phenotypic effect of Xq28 duplication size in MECP2 duplication syndrome.

Individuals with methyl CpG binding protein 2 (MECP2) duplication syndrome (MDS) have varying degrees of severity in their mobility, hand use, developmental skills, and susceptibility to infections. In the present study, we examine the relationship between duplication size, gene content, and overall phenotype in MDS using a clinical severity scale. Other genes typically duplicated within Xq28 (eg, GDI1, RAB39B, FLNA) are associated with distinct clinical features independent of MECP2. We additionally compare the phenotype of this cohort (n = 48) to other reported cohorts with MDS. Utilizing existing indices of clinical severity in Rett syndrome, we found that larger duplication size correlates with higher severity in total clinical severity scores (r = 0.36; P = 0.02), and in total motor behavioral assessment inventory scores (r = 0.31; P = 0.05). Greater severity was associated with having the RAB39B gene duplicated, although most of these participants also had large duplications. Results suggest that developmental delays in the first 6 months of life, hypotonia, vasomotor disturbances, constipation, drooling, and bruxism are common in MDS. This is the first study to show that duplication size is related to clinical severity. Future studies should examine whether large duplications which do not encompass RAB39B also contribute to clinical severity. Results also suggest the need for creating an MDS specific severity scale.

Outcomes and risk factors of massive and submassive pulmonary embolism in children: a retrospective cohort study

Little is known about severe pulmonary embolism in children. We aimed to report pulmonary embolism outcomes, identify risk factors for unfavourable outcomes, and evaluate the discriminative ability of two clinical-severity indices in children. In this retrospective cohort study, we included consecutive patients aged 18 years or younger with acute pulmonary embolism, objectively diagnosed radiologically or pathologically, between Jan 1, 2000, and Dec 31, 2016, from two Canadian paediatric hospitals (The Hospital for Sick Children, Toronto, ON, and the Children's Hospital of Eastern Ontario, Ottawa, ON). Exclusion criteria were sudden death without radiological or pathological pulmonary embolism confirmation and non-thromboembolic pulmonary embolism. The primary outcome was a composite of unfavourable outcomes of pulmonary embolism-related death and pulmonary embolism recurrence or progression. Potential predictors of the composite unfavourable outcome (ie, age at pulmonary embolism diagnosis, sex, underlying cardiac disease, severity of the pulmonary embolism, presence of a central venous catheter, associated venous thromboembolism, family history of thrombosis, treatment modalities, thrombophilia, obesity, and recent surgery) were explored with logistic regression. We calculated pulmonary embolism severity index (PESI) and simplified PESI (sPESI) using age-adjusted parameters; we estimated the ability of PESI and sPESI to predict mortality using receiver-operating characteristic (ROC) curve analysis. Of the 170 patients included, 37 (22%) had massive, 12 (7%) submassive, and 121 (71%) non-massive pulmonary embolism. Patients with massive or submassive pulmonary embolism were younger (median age 12·5 years [IQR 0·6-15·1] vs 14·4 years [9·3-16·1], p<0·0001), more likely to have a cardiac condition (16 [33%] vs 17 [14%] patients, p=0·009), and had more central venous catheters (29 [59%] vs 48 [40%] patients, p=0·027) than patients with non-massive pulmonary embolism. Aggressive treatment modalities were more commonly used in massive or submassive pulmonary embolism (22 [45%] vs 7 [6%] patients, p<0·0001). Of the predictors tested, only pulmonary embolism severity was associated with the composite unfavourable outcome in the multivariable analysis (odds ratio 3·53, 95% CI 1·69-7·36; p=0·011). The area under the ROC curve for PESI to predict 30-day mortality was 0·76 (95% CI 0·64-0·87). Sensitivity of sPESI was 100% and specificity was 30%. Massive or submassive pulmonary embolism led to higher rates of unfavourable outcomes than non-massive pulmonary embolism in children. Further adaptations of PESI and sPESI are required to improve their clinical usefulness in paediatric patients. Trainee Start-Up Fund (The Hospital for Sick Children).

Abstract WP1: Threshold Volume Associated With Higher Survival After Endovascular Recanalization Therapy of Acute Ischemic Stroke

Background and Purpose: Endovascular recanalization therapy (ERT) is becoming increasingly important in the management of acute ischemic stroke (AIS), but the hospital threshold volume for optimal ERT remains unknown. We investigated whether there was a correlation between hospital volume of ERT and risk-adjusted patient outcomes. Materials and Methods: From the National Health Insurance (NHI) claims data, we selected 11,745 AIS patients who underwent ERT from 2011 to 2015, in 111 hospitals. The outcome measures of the study were 30-day mortality, readmission rate, and symptomatic intracranial hemorrhage (ICH) rate. For each outcome measure, risk-adjusted mortality prediction models incorporating demographic variables, modified Charlson comorbidity index, and clinical stroke severity index (SSI) were built, and validated through a comparison with two independent hospital registry-based models. Hospitals were divided into quartiles and risk-adjusted outcomes of AIS cases were compared across the hospital quartile to confirm volume-outcome relationship (VOR) in ERT. Spline regression was performed to determine the volume threshold. Results: The mean AIS volume was 14.8 cases per hospital per year and the unadjusted means of outcome variables were mortality 11.6%, readmission 4.6%, and ICH rate 8.6%. The VOR was observed in the risk-adjusted 30-day mortality rate across all quartile groups, and in the ICH rate between the first and fourth quartiles ( p &lt; 0.05). Volume threshold was 24 cases per year, which was estimated by examining the relative effect on the adjusted odds of outcome for an increase in hospital volume by 10 cases/year for a hospital of a given size. Conclusions: We found an association between hospital volume and outcomes, and we identified the volume threshold in ERT. Policies to ensure the implementation of the AIS volume threshold for hospitals performing ERT is needed.

Acute pancreatitis and acute kidney injury in dogs

Acute pancreatitis and acute kidney injury are well-documented comorbidities in human medicine. Dogs that develop acute kidney injury during hospitalization have significantly higher mortality rates than those that do not. The aim of this study was to evaluate the prevalence of acute kidney injury in dogs with acute pancreatitis and the prognostic value of various clinicopathological parameters. Cases of acute pancreatitis presented between January 2012 and June 2016 were identified. The diagnosis of acute pancreatitis was based on two or more of the following clinical signs: abdominal pain, diarrhea, vomiting or anorexia/hyporexia, no other abdominal extra-pancreatic diseases at abdominal ultrasound, and abnormal SNAP cPL test. Diagnosis of acute kidney injury was based on the guidelines of the International Renal Interest Society. Dogs were classified into survivors and non-survivors. Serum creatinine, urea, amylase, total calcium, total cholesterol, C-reactive protein, WBC and band neutrophils were evaluated at admission. Clinical severity index was calculated at admission. Clinical and clinicopathological data were compared between survivors and non-survivors.Sixty-five dogs with acute pancreatitis were assessed. Clinical severity index≥6.5 were associated with poor outcome (P=0.0011). Serum urea and creatinine concentrations at admission were significantly lower in survivors than non-survivors (P<0.0001 and P=0.0002, respectively). Acute kidney injury was diagnosed in 17/65 dogs (26.2%) and was associated with poor outcome (P<0.0001). Oligo-anuria was associated with poor outcome (P=0.0294). Increased clinical severity index and azotemia in dogs with acute pancreatitis were associated with an increased risk of mortality. Acute kidney injury may be a comorbidity of canine acute pancreatitis. The presence of oligo-anuria is associated with poor outcome.

Increased interleukin-23 receptor (IL-23R) expression is associated with disease severity in acute-on-chronic liver failure.

Th17 cells mediated immune response is important in chronic hepatitis B (CHB) infection and inflammation associated diseases; however, little is known about their immunopathogenic role in acute-on-chronic liver failure (ACLF). Interleukin-23 receptor (IL-23R) is essential for the generation of pathogenic Th17 cells; therefore, we aimed to evaluate IL-23R expression and its correlation with disease severity in ACLF. Forty-two patients with ACLF (HBV and alcohol-related), thirty-two with CHB and twenty healthy controls (HC) were studied. Circulating and intrahepatic profile of Th17 cells and IL-23R was investigated. Association of IL-23R with disease severity was determined. Circulating Th17 cells were significantly increased in both ACLF groups (P=0.03, P=0.006) than CHB and HC. Percentage of Th17 cells was higher in liver than peripheral blood of ACLF patients (P=0.04). Expression of IL-23R was immensely up-regulated on Th17 cells of ACLF patients. Importantly, IL-23R not only correlated with the increased percentage of Th17 cells but also had significant association with inflammation (P=0.03) and clinical disease severity indices including Child-Turcotte-Pugh (P=0.001) and Model for End-Stage Liver Disease (P=0.002) scores. The ACLF non-survivors showed higher IL-23R expression (P=0.01). Transcription factor retinoic acid receptor-related orphan nuclear receptor gamma-t (ROR-γt) was also high in circulation and in liver of ACLF patients and it positively correlated with ALT levels (P=0.03). Surface receptors, including CCR6, IL-17R and pro-inflammatory cytokines IL-17A, IL-22, CXCL8 and GM-CSF were highly augmented in ACLF. ACLF patients express high IL-23R on Th17 cells which induces inflammation and strongly correlates with liver disease severity.

Variants in NLRP3 and NLRC4 inflammasome associate with susceptibility and severity of multiple sclerosis

BackgroundMultiple sclerosis (MS) is a neurodegenerative disease of central nervous system (CNS) with autoimmune and inflammatory characteristics, and a still uncertain pathogenesis. Early events as well as evolution of MS are heterogeneous (three main clinical forms) and multifactorial. Genome-wide association studies indicate that MS pathogenesis shares features with both autoimmune and inflammatory diseases. Innate immunity has been recently proved to be an important factor in MS. Genetic variants in inflammasome components have been associated with both autoimmune and neurodegenerative diseases, letting us hypothesize that inflammasome, and related cytokines IL-1ß and IL-18, could represent important contributors in MS pathogenesis, and eventually explain, at least in part, the heterogeneity observed in MS patients. AimTo evaluate the contribution of inflammasome in MS, in term of (a) genetic effect on development, severity and/or prognosis, and (b) complex activation in peripheral blood as a measure of systemic inflammation. MethodsFunctional genetic variants in inflammasome components were analyzed in a cohort of MS patients, by the use of allele-specific assays and qPCR. Multivariate analysis was performed based on clinical form (recurrent remittent/RR, primary progressive/PP or secondary progressive/SP), severity index (EDSS) and progression index (PI), response to IFN-ß treatment. Peripheral blood monocytes (PBM) of patients were examined for inflammasome activation and expression profile. Results and discussionVariants associated with low serum levels of IL-18 were significantly less frequent in MS patients than in controls, suggesting a protective role of diminished IL-18-mediate inflammation in MS development. On the other hands, gain-of-function variants in NLRP3 (Q705K) and IL1B (-511 C >T) associated with severity and progression of MS, suggesting that a constitutive activation of NLRP3 inflammasome could represent a risk factor for MS clinical presentation. Accordingly, -511C >T SNP resulted more frequent in progressive forms than in RR MS, reinforcing the idea that increased inflammasome activation characterized bad prognosis of MS. Altogether these findings corroborate previous data about the harmful role of NLRP3 inflammasome in experimental autoimmune encephalitis (EAE). Moreover, we reported for the first time the beneficial effect of NLRC4 rs479333 G >C variant in MS progression and in the response to IFN-ß treatment. This intronic polymorphism have been previously associated to decreased NLRC4 transcription and low IL-18 serum level, indicated once more that less activation of inflammasome and IL-18 production are beneficial for MS patients.PBM analysis showed that MS cells express higher level of inflammasome genes than HD ones, and are more prone to respond to a classical NLRP3 stimulus than HD.

ASCA (Anti-Saccharomyces cerevisiae Antibody) in Patients With Scleroderma.

The majority of scleroderma (SSc) patients present gastrointestinal involvement. Motility is usually compromised but few studies address permeability changes in the intestinal wall. ASCA (anti-Saccharomyces cerevisiae antibodies) positivity is associated with increased intestinal permeability. In this study we aimed to investigate ASCA positivity in SSc patients and its association with clinical, serological and epidemiological data. Seventy-four SSc patients and 57 healthy controls were studied for ASCA (IgG and IgA) positivity by ELISA. ASCA positivity was associated with demographic, clinical severity index (by Medsger score) and serological data in SSc patients. ASCA-IgG was positive in 32/74 (43.2%) patients of the SSc group and 1/57 (1.7%) of controls (p < 0.0001); ASCA-IgA was positive in 12/74 (16.2%) of the SSc group and 3/57 (5.2%) of controls (p = 0.05). In univariate analysis, ASCA-IgG presence was associated positively with African ethnic background (p < 0.001) and negatively associated with anticentromere antibodies (p = 0.013); ASCA-IgA had a negative association with Medsger score (p = 0.05). In multivariate analysis ASCA-IgG associated independently only with African ethnic background. Positivity for ASCA-IgG and ASCA-IgA is higher among scleroderma patients than controls. African descendants have more positivity for ASCA-IgG. ASCA-IgA is less frequent in patients with a more severe disease.

Understanding the severity of depression: Which symptoms of depression are the best indicators of depression severity?

BackgroundIn DSM-5, all symptoms of depression are considered equal representations of severity. In ICD-10, the type of symptom is considered in classifying severity. It is important to better understand if the defining symptoms of depression are differentially associated with overall severity so that severity categorization in diagnostic systems is most valid. In the present study from the Rhode Island Methods to Improve Diagnostic Assessment and Services (MIDAS) project we examined the association between the individual diagnostic criteria for major depressive disorder (MDD) and global ratings of depression severity. We thus examined whether there is support for the ICD-10 approach in which some symptoms are better indicators of severity than are other symptoms. MethodsPatients were evaluated with a semi-structured interview and the presence of each symptom of MDD was recorded. Patients were also rated on the Clinical Global Index of severity (CGI-S). ResultsAll 9 DSM-5 criteria were significantly correlated with the CGI with suicidality having the highest correlation. A regression analysis found that all 9 criteria were significant predictors of the CGI. At the symptom level, 15 of the 17 symptoms were significantly correlated with the CGI (all except increased appetite and increased weight). DiscussionThere were differences between the symptoms of depression in their association with severity with suicidal ideation, depressed mood, and anhedonia having the highest correlations with severity whereas some symptoms were not significantly associated with severity distinctions. Future descriptions of the severity of depression should not consider all criteria as equal representations of severity.