BA Patients Research Articles

Biliary atresia liver histopathological determinants of early post-Kasai outcome

BackgroundA retrospective chart review of liver histologies in Kasai biliary atresia BA patients operated 1/2017- 7/2019 at our institution was conducted to identify histologic prognostic factors for biliary outcome. MethodsPatients with wedge liver biopsies and portal plate biopsies (n = 85) were categorized into unfavorable and favorable outcome, based on a 3-month serum total bilirubin level of <34 μM or mortality. Hepatocellular histologies, presence of ductal plate malformation (DPM) and of large bile duct of ≥ 150 μm diameter size at the portal plate were evaluated. ResultsTotal Bilirubin levels> 34 μM correlates with worse 1-year survival. Age at surgery, histologic fibrosis or inflammation does not predict outcome. Potential adverse predictors are severe hepatocellular swelling, severe cholestasis, presence of DPM (n = 24), and portal plate bile duct size < 150 µm (n = 28). In multivariate analyses adjusting for age at Kasai and postop cholangitis, bile duct size and severe hepatocellular swelling remain independent histologic prognosticators (OR 3.25, p = 0.039 and OR 3.26, p = 0.006 respectively), but not DPM. ConclusionAdvanced histologic findings of portal plate bile duct size of <150 µm and severe hepatocellular damage predict poor post-Kasai jaundice clearance and short-term survival outcome, irrespective of Kasai timing.Level of Evidence: Level III

Leukocyte indices of patients with bronchial asthma: informative significance of use

Determination of informativeness of leukocyte indices in patients with bronchial asthma, who have comorbid diseases in clinical remission of asthma. The work based on a single examination of 225 patients with bronchial asthma. Criteria for inclusion in the study are following: the presence of a verified diagnosis of bronchial asthma, the phase of clinical remission. The patients have been divided into 4 groups, taking into account the type of comorbid diseases: the 1 group (53 patients) bronchial asthma was combined with lesions of the upper gastrointestinal tract; the 2 group (73 patients) with allergic rhinitis; the 3 group (76 patients) with hypertension; the 4 group (23 patients) comparison group: the patients without comorbid pathology. According to the clinical blood analysis, 10 leukocyte indices were calculated for each group of patients and their values were analyzed taking into account the frequency and severity of deviations from the reference values. Mathematical processing of the material was carried out using the statistical software package SPSS13.0 for Windows. Using leukocyte indices, it has been revealed that even during the period of clinical remission, almost all examined patients with BA have endogenous intoxication, the severity of which increases in comorbid diseases. Intoxication was inflammatory in nature and, according to the data of leukocyte indices, was due to the presence of persistent inflammation (local and systemic) and during clinical remission. Violation of immunological reactivity has been revealed in most of the examined patients. The presence of correlation relationships of leukocyte indices with a number of biochemical and immunological indicators allows one to exclude the latter from the plan of examination of patients without reducing the quality of their examination: for example, in the conditions of polyclinics, small hospitals, and resorts. Eight leukocyte indices that are the most informative at BA have been selected. Additional information about the condition of BA patients who have comorbid diseases during clinical remission can be used to develop programs for their comprehensive treatment and rehabilitation.

Abstract PO-222: Co-morbid risk factors and NSAID use among white and black Americans that predicts overall survival from diagnosed colon cancer

Abstract Black Americans (BA) have higher incidence and higher mortality rates for colorectal cancers (CRC) as compared to White Americans (WA). While there are several identified risk factors associated with the development of CRC and evidence that high levels of adequate screening can reduce differences in incidence for CRC between BA and WA, there remains little data regarding patient co-morbid contributions towards survival once an individual has CRC. Here we set out to identify patient risk factors that influenced overall survival in a cohort of 293 BA and 348 WA with colon cancer, ages 40 to 84 years old, with at least 10 years of follow- up. We utilized the logistic regression test for statistical associations, the Kaplan- Meier method with log rank test for survival analyses, and Cox Proportional Hazards Models for covariate independence. Amid our cohort, we found that patients’ age, tobacco usage, and pre-diagnosed medical conditions such as hypertension and diabetes were associated with shorter overall survival (OS) from colon cancer. We identified pre-diagnosed hypertension (19.6% contribution) and diabetes (12% contribution) among BA were together responsible for nearly one-third of the colon cancer mortality disparity compared with WA. We also identified long-term regular use (&amp;gt;5 years aggregated years of drug use) of non-steroidal anti-inflammatory drugs (NSAIDs), including aspirin, was associated with shorter OS from colon cancer among WA &amp;gt;65 years of age (Hazard Ratio 1.76, 95% confidence interval 1.12-2.77), but not younger WA patients or any aged BA patients. Our results raise the importance of not only treating the colon cancer itself, but also taking into consideration co-morbid medical conditions and NSAID usage to enhance patient OS. Further evaluation regarding adequate treatment of co-morbidities and timing of NSAID continuance after cancer therapy will need to be studied. Citation Format: Minoru Koi, Yoshiki Okita, Erika Koeppe, Elena M. Stoffel, Joseph A. Galanko, Nikki McCoy, Temitope Keku, John M. Carethers. Co-morbid risk factors and NSAID use among white and black Americans that predicts overall survival from diagnosed colon cancer [abstract]. In: Proceedings of the AACR Virtual Conference: Thirteenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2020 Oct 2-4. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(12 Suppl):Abstract nr PO-222.

Decreased circulating clusterin reflects severe liver complications after hepatoportoenterostomy of biliary atresia

This study aimed to determine whether circulating levels of clusterin (CLU), an extracellular chaperone implicated in cholestatic and fibrotic processes, are associated with clinical parameters of post-operative BA patients and could serve as a BA biomarker. Ninety-six BA patients and 56 healthy controls were recruited. Circulating CLU levels were measured using enzyme-linked immunosorbent assay. Circulating CLU levels were significantly reduced in BA patients – especially those with worse outcomes including jaundice, severe liver fibrosis, and late-stage of hepatic dysfunction. Multivariate linear regression analysis revealed that circulating CLU levels were negatively associated with outcome parameters indicating jaundice status, degree of fibrosis, and liver dysfunction, but positively correlated with serum albumin and platelet number of BA patients. Lower circulating CLU levels were considerably associated with poor survival of post-operative BA patients. Receiver-operating characteristic curve analysis demonstrated a diagnostic value of circulating CLU as a non-invasive indicator for poor outcomes of BA patients (AUC = 0.85), with a sensitivity of 81.5% and a specificity of 73.5%. All findings indicate that reduced circulating CLU might reflect poor outcomes of BA patients and have potential as a novel biomarker for the disease severity following Kasai-operation.

Serum Heat Shock Protein 90 in Diagnosis of Biliary Atresia

Punctual ID number for biliary atresia (BA) may be key. Dependable non-invasive instruments for finding are needing. High temperature stun protein 90 an adenosine triphosphate subordinate sub-atomic chaperone that is included to hepatobiliary conversion. Those available investigation plans should assess its part in analysis from claiming ba. What added up to 90 babies were included in the examine. They comprised 30 babies with BA, 30 babies for non-BA cholestasis Also 30 Obviously period Also sex matched solid babies who were selected Concerning illustration controls. Babies diagnosed for ba alternately different non-BA cholestasis were incorporated in the consider on the foundation from claiming clinical pattern, cholangiogram, Also histological discoveries. After full historical backdrop taking What's more careful clinical examination, the finding for ba might have been affirmed Eventually Tom's perusing intraoperative cholangiography. Other investigations incorporated downright Also immediate bilirubin, aggregate proteins, albumin, ALT, AST, ALP, GGT, prothrombin time, worldwide normalized proportion (INR), finish blood count, light race antibodies, ultrasonography examination Furthermore liver biopsy. Serum levels about HSP90 might have been evaluated utilizing elisa method. It might have been discovered that ba patients needed essentially higher HSP90 levels when compared with non-BA patients Also sound controls (BA: 671. 0 (309. 7-803. 0, non-BA: 151. 5 (120. 5-172. 7), controls: 55. 0 (26. 5-68. 7) pg/ml, p < 0. 001). In An cut-off from claiming 195. 5 pg/ml, HSP90 indicated phenomenal affectability and specificity to recognizing ba starting with non-BA patients (AUC: 0. 982, p

Th17-associated cytokines multiplex testing indicates the potential of macrophage inflammatory protein-3 alpha in the diagnosis of biliary atresia

Background & aimsBiliary atresia (BA) is a neonatal obliterative cholangiopathy with high prevalence in south China. Accurate identification of BA among infants with obstructive jaundice is still difficult by noninvasive diagnostic tools. Th17 cells have been reported closely related with the development of BA, which suggest that Th17-associated cytokines were potential biomarkers for the diagnosis of BA patients. MethodsIn the training study, 76 infants who were divided into 2 groups, including BA group (n = 31) and non-BA jaundice group (n = 45). Clinical and routine laboratory data were collected from all subjects. Totally 25 Th17-associated cytokines were tested and compared between groups. The diagnostic value of each differential cytokine was evaluated by the area under the receiver operating characteristic curve (AUC). The best potential diagnostic biomarker was further validated in a cohort including 68 jaundice infants from our partnering institution in a blinded fashion. ResultsData from the training study showed that gamma-glutamyl transferase (GGT) and clay stool would be helpful in the identification of BA patients in jaundice subjects. Th17-associated cytokines assay indicated that IL-17F, IL-10, macrophage inflammatory protein-3alpha (MIP3a), IL-22, IL-13, IL-33, IL-6, IL-17E, IL-27, IL-31, TNF-a and TNF-b were differentially expressed in BA patients, and the AUC of MIP3a was higher than other markers. MIP3a alone or combined with other laboratory data would significantly increase the diagnostic accuracy of BA. The diagnostic value of MIP3a was further confirmed in our validation study. ConclusionMIP3a alone or combined with other laboratory data would significantly increase the diagnostic accuracy of BA.

Biliary atresia: 20–40-year follow-up with native liver in an Italian centre

IntroductionBiliary atresia (BA) represents the leading indication for liver transplantation in childhood. Only few studies reported the outcome of patients who survived more than 20 years on their native liver, and up to date there are no Italian data available. We reported our 40-year single centre experience with long-term follow-up of BA patients. Materials and methodsAll consecutive patients who underwent Kasai portoenterostomy (KPE) for BA managed at our Institution between 1975 and 1996 were retrospectively reviewed. Native liver (NLS) and overall survival (OS) were analyzed with Kaplan-Meyer curves and LogRank test. A p value of <.05 was regarded as significant. Quality of life of patients currently surviving with their native liver was assessed through a quality of life questionnaire. ResultsDuring the 22-year period of the study 174 patients underwent surgery (median age 60 days). Clearance of jaundice at 6 months from surgery was achieved in 90 patients (51.7%). NLS was 41% at 5 years, 32% at 10 years, 17.8% at 20 years and 14.9% at 40 years. Cholangitis was recorded in 32%, hepatocellular carcinoma in 0.5%. Twenty-six patients (14.9%) survived with their liver more than 20 years; 84.6% had normal serum bilirubin level and 23% had esophageal varices. Quality of life was comparable with the healthy Italian population in all but one patient. ConclusionsOur Italian experience confirms KPE represents the cornerstone of treatment for children with BA. Multidisciplinary and meticulous lifelong post-operative follow-up should be guaranteed for these patients because of the possibility of late-onset cholangitis, portal hypertension, hepatic deterioration and liver malignant tumors. Type of the studyretrospective case series. Level of evidenceIV.

Long-term outcome and necessity of liver transplantation in infants with biliary atresia are independent of cytokine milieu in native liver and serum

PurposeBiliary atresia (BA) is a rare disease of unknown pathogenesis in infants characterized by an inflammatory, progressive destruction of the biliary system and deterioration of liver function. The standard treatment for BA is a Kasai-hepatoportoenterostomy (KPE). However, liver transplantation (LTX) becomes necessary in about 50–80% of cases. Therefore, some authors advocate for primary LTX in BA, but this would require early markers to predict which children would benefit from KPE or to show rapid progression to liver cirrhosis (RLC) instead. MethodsSnap-frozen liver biopsies and sera samples of 57 infants with BA were collected during KPE. Clinical and follow-up data were assessed via the biliary atresia and related diseases registry (BARD-online.com). Protein-levels of 25 pro- and anti-inflammatory mediators of 49 infants were assessed via multiplex protein-immunoassay and analyzed by t-test as well as multidimensional principal component analysis. Results22 different immunomodulatory mediators were detectable in livers of children with BA, while serum protein levels were very low to undetectable. Following KPE, 33 BA patients showed RLC that required early LTX, while 24 had favorable course of disease with long-term survival with native liver (SNL). There were no significant differences between RLC and SNL in terms of local (from liver samples) nor systemic (from sera) immunomodulatory mediators. Protein levels were much lower in sera than in livers without statistical correlation. ConclusionOur data suggest that local or systemic immunomodulatory mediators are unsuitable for predicting the disease course of BA. Thus, no deduction for optimal treatment strategy can be drawn. Collectively, we conclude that in BA, the degree of inflammation and protein microenvironment in the liver at the time-point of KPE are dismissible factors for the future course of disease.

Liver graft-to-spleen volume ratio as a useful predictive factor of the early graft function in children and young adults transplanted for biliary atresia: a retrospective study.

A graft volume/standard liver volume ratio (GV/SLV) > 35% or graft/recipient weight ratio (GRWR) > 0.8% has been considered as a standard criteria of graft selection. Even if the graft size meets these selection criteria, small-for-size syndrome can still occur depending on the portal venous flow (PVF). The aim of this study was to identify other factors contributing to portal hyperperfusion and the post-transplant course, focusing on the graft volume-to-spleen volume ratio (GV/SV). Thirty-seven BA patients who underwent living donor liver transplantation were reviewed retrospectively. First, we evaluated the preoperative factors contributing to portal hyperperfusion. Second, we evaluated the factors contributing to post-transplant complications, such as thrombocytopenia, hyperbilirubinemia, and coagulopathy. The GV/SLV was >35% in all cases; however, portal hyperperfusion (≥250 ml/min/100 g graft) was found in 12 recipients (35.3%). Furthermore, although the GRWR was >0.8% in over 90% of cases, portal hyperperfusion was found in 10 recipients (32.3%). In contrast, the GV/SV showed a significant correlation with the PVF after reperfusion. If the GV/SV was <0.88, about 80% of recipients developed portal hyperperfusion. Furthermore, the GV/SV also showed a significant correlation with post-transplant persistent thrombocytopenia and hyperbilirubinemia. The GV/SV < 0.88 predicts portal hyperperfusion, post-transplant persistent thrombocytopenia, and hyperbilirubinemia.

CLINICAL-GENETIC PHENOTYPING BRONCHIAL ASTHMA

Objective – to determine BA phenotypes using cluster analysis based on clinical and genetic traits in the Ukrainian population. Materials and methods. The study involved 195 patients with asthma. The diagnosis of asthma was made on the basis of the recommendations of GINA (2016) and order № 868 of 08.10.2013 of the Ministry of Health of Ukraine. To assess the control of asthma, an ACQ-5 questionnaire was used. The function of external respiration (FVD) was studied by means of the diagnostic complex Cardioplus (Ukraine) and the results were evaluated according to national recommendations. All patients underwent a reversibility test using 4 inhalations of salbutamol (400 μg). For the cluster analysis, 24 variables were used – clinical and instrumental, anamnestic and genetic parameters. For the cluster analysis, the SPSS-21 program was used. Gln27Glu (rs1042714) polymorphism of the ADRB2 gene was determined using the polymerase chain reaction method. The control group for the genetic study was 95 practically healthy persons without allergopathology. Results. Using the cluster analysis, we identified 3 phenotypes of BA: the 1-st phenotype (cluster A, n=81) − allergic asthma which occurs at a young age with a partially controlled course and a good response to inhaled glucocorticoids (IGCC) and β2-agonists long-acting (LABA); the 2-nd phenotype (cluster B, n=38) − non-allergic asthma, most of the women with overweight are characterized by an onset of BA at young age with uncontrolled course and inadequate response to medium doses of IGCC and LABA; the 3-d phenotype (cluster C, n=76) − non-allergic asthma which is associated with obesity diagnosed predominantly in women and has a partially controlled course. Conclusions. Carriers of the Glu27Glu genotype were more frequent among BA patients from cluster B, Gln27Glu genotype − in BA patients from cluster A and C, and Gln27Gln genotype − in BA patients from cluster A. The risk of BA was 5.5 times higher in carriers of Glu allele in comparison with carriers of the Gln allele of Gln27Glu polymorphism of ADRB2.

THE FUNCTIONAL STATUS OF NEUTROPHILS IN PATIENTS WITH BRONCHIAL ASTHMA, CHRONIC OBSTRUCTIVE PULMONARY DISEASE, BRONCHIAL ASTHMA IN COMBINATION WITH CHRONIC OBSTRUCTIVE PULMONARY DISEASE AND COMMUNITY-ACOUIRED PNEUMONIA

217 people were examined including BA patients (n=78), patients with COPD (n=38), patients with combined asthma and COPD (n=39), and community-acquired pneumonia patients (n=17). The control group represented patients with essential hypertension and coronary heart disease (n=25) and 20 healthy persons. NE, AAT, phagocytic activity of neutrophils (FGC), oxygen blast, respiratory function and FeNO, serum IgE and IgG antibodies to Strept. pneumoniae, Neisseria perflava, Haemofil. influenzae and Staph. aigai were determined in all patients. The indicators of the functional state of neutrophils reflected the degree and severity of bronchopulmonary inflammation. Patients with bronchial asthma in combination with COPD had bacterial inflammation, manifested by bronchial obstruction with increasing level of AAT. These features were absent in patients with BA and COPD.

Laparoscopic portoenterostomy for biliary atresia: single-center experience and review of literatures.

The aim of this report was to present the laparoscopic portoenterostomy (LapPE) procedure developed by the Department of Pediatric General and Urogenital Surgery, Juntendo University School of Medicine (JLapPE). We also attempted to obtain an understanding of the current status of laparoscopic portoenterostomy in the world as reported in the English literature to compare with our experience. There were 22 BA patients who had JLapPE between 2009 and 2016. BA classification was type III (n = 19) and type II (n = 3). There was 1 case of syndromic BA and 1 case was positive for cytomegalovirus. A systematic search in PubMed of all BA patients treated by LapPE in the English literature was conducted. Jaundice clearance (JC) and survival with the native liver (SNL) were compared. Mean age at JLapPE was 67.1days (range 29-119). Mean postoperative follow-up was 4.6years (1.3-8.3). Mean operative time was 514min (240-662) and mean blood loss was 13.4g (3-21). Postoperative JC (Total bilirubin ≤ 1.5mg/dL) was 77.3% (17/22) at 3months and 90.9% (20/22) at 6months. SNL at 6months of age was 90.9% (20/22); at 1year of age was 77.3% (17/22), at 2years of age was 73.7% (14/19); and at 3years of age was 81.3% (13/16). Despite recent reports that outcome of LapPE for BA may be unfavorable compared with the conventional open portoenterostomy, our results would suggest that JLapPE can be performed successfully, because it is performed exactingly according to a standard protocol. JLapPE will continue to be our procedure of choice for treating BA.

Catalase C-262T Gene Variant in Patients with Bronchial Asthma

Summary Bronchial asthma (BA) is a chronic inflammatory disease of the airways in the pathogenesis of which oxidative stress has a very important role. Single nucleotide polymorphisms (SNPs) in catalase gene may result in decreased antioxidative defense capacity, and thus a higher risk for BA development. Since oxidative stress has an important role in the pathogenesis of BA and catalase has a key role in antioxidant defense, the aim of this study was to examine the association of CAT C-262T polymorphism with BA in Serbian patients with BA. A total of 170 subjects (79 patients with BA and 91 controls) were screened for CAT C-262T SNP using PCR-RFLP method. The analysis of genotype distribution did not show statistically significant differences between BA patients and controls (p &gt; 0.05). Moreover, no differences were detected when comparison was performed based on dominant or recessive model. The distribution of CAT-262C and CAT-262T alleles did not show differences between patients and healthy controls (p = 0.715; OR = 1.091; 95% CI = 0.684–1.741). Further analysis of genotype and allele distributions, based on stratification by sex, did not show significant differences between BA patients and controls (p &gt; 0.05). This is the first study that examined CAT C-262T (rs1001179) SNP in Serbian patients with BA. The results obtained in this study showed that biallelic SNP at the position-262 in the catalase gene is not associated with BA in the Serbian population.

Abstract 161: Lean Process Improvements Reduce Door to CT and Door to Needle Times for Acute Ischemic Stroke Patients

Background: In late 2015, we assembled a multi-disciplinary team to analyze current emergency department (ED) processes and identify improvement opportunities in the current “brain attack” (BA) protocol. Using lean process engineering tools, including time study analysis, gemba walks, and cause and effect diagrams, we mapped our baseline state and identified delaying activities that did not add value to the BA process. We defined a new BA process (see Figure 1) to eliminate waste and improve team communication, including 3 Time Outs to ensure that increased speed didn’t decrease safety. Methods: To determine the effect of our intervention, we retrospectively reviewed patients who were admitted to our ED as a BA for evaluation of possible acute ischemic stroke and had a CT brain after ED arrival between April 2015 and August 2016. ED arrival was defined as the time that patients physically arrived at the ED and “time to CT” was the time from ED arrival to the first time stamp of the CT brain. The time from ED arrival to tPA bolus was also measured for "door to needle" time. The time to CT and door to needle times were compared between BA patients before and after lean process improvements using Student’s T-test. Results: Our cohort included 239 patients who presented to the ED as a BA. We included 116 BA patients from before the intervention and 123 from afterwards. The mean±SD time to CT prior to the intervention was 19.0±13.9 minutes. After our lean process improvements the time to CT was 14.2±15.6 minutes. The delta of 4.8 minutes resulted in a significant reduction in time to CT, p = 0.012. There were 14 patients who received tPA prior to the intervention and 9 afterwards, for a total of 23 door to needle times (10% of cohort). Door to needle time was significantly shortened post-intervention (46±13 minutes versus 32±12 minutes, p=0.013). Conclusions: Lean process improvement methodology significantly reduces door to CT and door to needle times, supporting current AHA Target: Stroke goals and allowing faster treatment of patients with acute ischemic stroke. Incorporating time-outs into standardized processes that aim to deliver care more quickly may improve patient safety without substantially slowing down DTN times. Further investigation is required to determine whether the new process improved safety and clinical outcomes.

Expression of fibroblast growth factor 21 in patients with biliary atresia

Fibroblast growth factor 21 is a critical circulating adipokine involving in metabolic disorders and various liver diseases. This study was performed to investigate whether FGF21 is also associated with the pathophysiology of biliary atresia. Serum FGF21 levels were measured in 57 BA patients and 20 age matched healthy controls. We also examined hepatic FGF21 mRNA expression and FGF21 protein levels in liver tissues obtained from 15 BA patients undergoing liver transplantation and 5 cases of pediatric donation after cardiac death donor without liver diseases by RT-PCR and Western blotting. Patients with BA showed significantly higher serum FGF21 levels than those without BA (554.7pg/mL [83–2300] vs. 124.5pg/mL [66–270], P<0.05). Patients with BA also had significantly higher FGF21 mRNA and protein levels in hepatic tissues than control subjects. Serum FGF21 expression increased corresponding to the severity of liver fibrosis. Furthermore, serum FGF21 levels dropped significantly in BA patients within 6months after liver transplantation and approached baseline in healthy controls (P>0.05). In vivo, FXR knockout could significantly abrogate cholestasis induced FGF21 expression. FGF21 levels in serum and liver tissue increased significantly in BA patients. In vivo, cholestasis could induce FGF21 expression in FXR dependent manner.

Hepatic ADC map as an adjunct to conventional abdominal MRI to evaluate hepatic fibrotic and clinical cirrhotic severity in biliary atresia patients.

Hepatic apparent diffusion coefficient (ADC) values and ADC-related indices were correlated with the Mayo risk score for primary biliary cirrhosis (MRSPBC) and METAVIR scores of liver specimens to determine the clinical and pathological significance of diffusion-weighted magnetic resonance imaging (DWMRI). Thirty-two patients with biliary atresia (BA; mean age 461 days, range 11-4616 days) received magnetic resonance examinations from March 2009 to August 2013. A free-breathing DWMRI sequence was performed with the single-shot echo-planar imaging technique with b = 0 and 500 s/mm(2) in all 32 BA patients and 24 controls. We used the ordinal logistic regression test and Spearman rank correlation test to analyse the relationships between the MRSPBC and METAVIR fibrosis scores and right liver-to-psoas ADC ratios (LTPARs). BA patients had significantly lower LTPARs in both hepatic lobes than controls (p < 0.01). Right LTPARs, showing moderate intraobserver agreement (intraclass correlation coefficient = 0.736) and interobserver reliability (intraclass correlation coefficient = 0.659), were negatively correlated with MRSPBC and METAVIR fibrosis scores (R(2) = 0.398, p = 0.024 and R(2) = 0.628, p < 0.001, respectively). Right LTPARs may be used for long-term follow-up of cirrhosis severity in BA patients. • Hepatic ADC values by DWI correlates well with clinical/pathologic fibrosis scores • Periodic, non-invasive, quantitative imaging follow-up of patients with biliary cirrhosis is feasible • Information on cirrhosis severity could help decide on management options in children with BA • ADC values may be useful in this regard.

INFLUENCE OF CYTOMEGALOVIRUS PERSISTENCE UPON CLINICAL COURSE OF BRONCHIAL ASTHMA (BA) IN CHILDREN

We have performed a study of 117 children (106 with BА, and 11, a comparison group). Upon examination of BA patients, they exhibited high rates of pneumotropic intracellular infections more frequent is found out, in comparison with healthy children, endocellular infection pathogens, in particular, cytomegalovirus (CMV), as shown by more frequent detection of specific IgM, IgG, and detection of virus-specific DNA in sputum samples of the sick children suffering with BA. In the children with BА shedding CMV DNA with sputum, a more severe clinical course of the disease was shown, as evidenced by more frequent bronchial obstruction episodes, and more severe symptoms. Decreased levels of all lymphocyte subpopulations was revealed in the patients, but in CMV-positive children, this drop was more pronounced, and accompanied by increase in CD4+ and decrease in CD8+ subpopulations, higher levels of IgA, IgM, and IgG, as well as stronger phagocytic activity. Exacerbation of BA significantly correlates with CD8+ numbers, along with correlations between presence of anti-CMV IgG and amounts of CD16+, CD16a+ cells.

Evaluating the technique of using inhalation device in COPD and Bronchial Asthma patients

In asthma management, poor handling of inhalation devices and wrong inhalation technique are associated with decreased medication delivery and poor disease control. The key to overcome the drawbacks in inhalation technique is to make patients familiar with issues related to correct use and performance of these medical devices. The objective of this study was to evaluate and analyse technique of use of the inhalation device used by patients of COPD and Bronchial Asthma. A total of 300 cases of BA or COPD patients using different types of inhalation devices were included in this observational study. Data were captured using a proforma and were analysed using SPSS version 15.0. Out of total 300 enrolled patients, 247 (82.3%) made at least one error. Maximum errors observed in subjects using MDI (94.3%), followed by DPI (82.3%), MDI with Spacer (78%) while Nebulizer users (70%) made least number of errors (p=0.005). Illiterate patients showed 95.2% error while post-graduate and professionals showed 33.3%. This difference was statistically significant (p<0.001). Self-educated patients committed 100% error, while those trained by a doctor made 56.3% error. Majority of patients using inhalation devices made errors while using the device. Proper education to patients on correct usage may not only improve control of the symptoms of the disease but might also allow dose reduction in long term.

Brain abscess: Current management

Brain abscess (BA) is defined as a focal infection within the brain parenchyma, which starts as a localized area of cerebritis, which is subsequently converted into a collection of pus within a well-vascularized capsule. BA must be differentiated from parameningeal infections, including epidural abscess and subdural empyema. The BA is a challenge for the neurosurgeon because it is needed good clinical, pharmacological, and surgical skills for providing good clinical outcomes and prognosis to BA patients. Considered an infrequent brain infection, BA could be a devastator entity that easily left the patient into dead. The aim of this work is to review the current concepts regarding epidemiology, pathophysiology, etiology, clinical presentation, diagnosis, and management of BA.

Interleukin-32 production associated with biliary innate immunity and proinflammatory cytokines contributes to the pathogenesis of cholangitis in biliary atresia

Biliary atresia (BA) is thought to be associated with infections by viruses such as Reoviridae and is characterized histologically by fibrosclerosing cholangitis with proinflammatory cytokine-mediated inflammation. Interleukin (IL)-32 affects the continuous inflammation by increasing the production of proinflammatory cytokines. In this study, the role of IL-32 in the cholangitis of BA was examined. Immunohistochemistry for IL-32 and caspase 1 was performed using 21 samples of extrahepatic bile ducts resected from BA patients. Moreover, using cultured human biliary epithelial cells (BECs), the expression of IL-32 and its induction on stimulation with a Toll-like receptor [(TLR)-3 ligand (poly(I:C)] and proinflammatory cytokines was examined. BECs composing extrahepatic bile ducts showing cholangitis expressed IL-32 in BA, but not in controls. Caspase 1 was expressed constantly on BECs of both BA and control subjects. Furthermore, poly(I:C) and proinflammatory cytokines [(IL-1β, interferon (IFN)-γ and tumour necrosis factor (TNF)-α] induced IL-32 expression strongly in cultured BECs, accompanying the constant expression of TLR-3 and caspase 1. Our results imply that the expression of IL-32 in BECs was found in the damaged bile ducts of BA and induced by biliary innate immunity via TLR-3 and proinflammatory cytokines. These findings suggest that IL-32 is involved initially in the pathogenic mechanisms of cholangitis in BA and also plays an important role in the amplification and continuance of periductal inflammatory reactions. It is therefore tempting to speculate that inhibitors of IL-32 could be useful for attenuating cholangitis in BA.