PT Score Research Articles

Abstract PO4-16-02: Can high progesterone receptor (PgR) expression identify tumours with low-risk tumour gene expression scores?

Abstract Background Strong PgR expression predicts favorable outcomes for ER+ve HER2-ve breast cancer and has been proposed as a surrogate marker to distinguish between IHC-defined luminal A and luminal B subtypes. It is therefore possible that strong PgR expression may be able to predict tumor gene expression test results and independently identify tumors that are unlikely to be chemotherapy sensitive. PgR expression is traditionally determined by immunohistochemistry (IHC). Several validated RNA-based PGR expression tests have been developed that may outperform IHC. Methods We compared Oncotype DX RS with Oncotype DX reported PGR in 4 independent datasets which included 407 cases from the OPTIMA prelim trial. We further analyzed 251 OPTIMA prelim cases which had additional tumor gene expression data. All gene expression assays were performed by the test vendor, including PGR gene expression determined using the Mammatyper assay. PgR IHC was determined in a single laboratory on triplicate tissue micro-arrays using quantitative image analysis including a 10% manual quality control check. We analyzed PGR expression using cutoffs that correspond to approximately 20% staining; the standard Oncotype DX PGR assay is reported as positive if the score is >5.4, corresponding to approximately 1% staining by IHC. We used Spearman’s rank correlation coefficient to compare PGR data. Results The four Oncotype DX datasets consistently demonstrated that high Oncotype PGR expression was associated with a low RS (table). Combining the 3 validation data sets consisting of 633 cases, 70.9% had high PGR expression of which 92.7% had a an Oncotype RS ≤25. Approximately 50% of cases with low Oncotype PGR expression had an Oncotype RS >25. Mammatyper and Oncotype PGR were highly correlated (Rs = 0.9258, P< 0.001) in the OPTIMA prelim dataset (n=251), with only 8.4% of tumors having discordant high/low Mammatyper and Oncotype PGR scores. 93.2% of 176 Mammatyper high PGR expression cases had an RS ≤25. The Mammatyper PGR and PgR IHC correlation was weaker (Rs=0.763, P< 0.001); 87.2% of 211 cases with >20% staining had RS ≤25. PgR IHC staining had a bimodal distribution and there was little effect on the prediction of low RS score up to a 67% cut-off. Mammatyper and Oncotype PGR scores both appear to have a normal distribution. We took advantage of this to perform an exploratory analysis using a higher Mammatyper PGR cutoff. We were able to show superior prediction of a low RS (96.8%) but with a reduced proportion (50.2%) of high PGR score tumors. High PGR gene expression was weakly associated with low (≤60) Prosigna ROR_PT score and MammaPrint low risk (72.2% and 65.9% respectively) and with Prosigna and MammaPrint luminal A subtype (both 64.8%). Conclusion High progesterone receptor gene expression measured using locally performed RNA-based assays may allow the reliable prediction of Oncotype DX low-risk tumours. This analysis provides additional information for the clinical utility of PGR measurement. Additional data will be presented on the optimal PGR cutoff. OPTIMA prelim is registered as ISRCTN42400492 and funded by the UK NIHR Health Technology Assessment Programme, award number 10/34/01. Views expressed are those of the authors and not those of the HTA Programme, NIHR, NHS or the Department of Health. Table. Oncotype DX RS and PGR in 4 datasets Distribution of RS according to %cases with high or low PGR Citation Format: Robert Stein, Ralph Wirtz, Andrea Marshall, Jane Bayani, Sebastian Eidt, Claudia Schumacher, Hans-Peter Sinn, Andreas Schneeweiss, Andreas Makris, Iain Macpherson, Luke Hughes-Davies, Tammy Piper, Monika Sobol, Georgina Dotchin, Helen Higgins, Sarah Pinder, Abeer Shaaban, Janet Dunn, John MS Bartlett. Can high progesterone receptor (PgR) expression identify tumours with low-risk tumour gene expression scores? [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-16-02.

Constructing an early-warning model for mortality risk in heat stroke patients based on Fisher discriminant analysis

Objective: To establish an early warning model to assess the mortality risk of patients with heat stroke disease. Methods: The case data of patients diagnosed with heat stroke disease admitted to the comprehensive ICU of Shanshan County from January 2016 to December 2020 were selected. According to the short-term outcome (28 days) of patients, they were divided into death group (20 cases) and survival group (53 cases) . The relevant indicators with statistically significant differences between groups within 24 hours after admission were selected. By drawing the subject work curve (ROC) and calculating the area under the curve, the relevant indicators with the area under the curve greater than 0.7 were selected, Fisher discriminant analysis was used to establish an assessment model for the death risk of heat stroke disease. The data of heat stroke patients from January 1, 2021 to December 2022 in the comprehensive ICU of Shanshan County were collected for external verification. Results There were significant differences in age, cystatin C, procalcitonin, platelet count, CKMB, CK, CREA, PT, TT, APTT, heart rate, respiratory rate and GLS score among the groups. Cystatin C, CKMB, CREA, PT, TT, heart rate AUC area at admission was greater than 0.7. Fisher analysis method is used to build a functional model. Results: The diagnostic sensitivity, specificity and AUC area of the functional model were 95%, 83% and 0.937 respectively. The external validation results showed that the accuracy of predicting survival group was 85.71%, the accuracy of predicting death group was 88.89%. Conclusion: The early warning model of heat stroke death constructed by ROC curve analysis and Fisher discriminant analysis can provide objective reference for early intervention of heat stroke.

Abstract OT3-32-01: OPTIMA, a prospective randomized trial to validate the clinical utility and cost-effectiveness of gene expression test-directed chemotherapy decisions in high clinical risk early breast cancer

Abstract Background: Multi-parameter tumor gene expression assays (MPAs) are used to estimate individual patient risk and guide chemotherapy use in hormone-sensitive, HER2-negative early breast cancer. The TAILORx trial supports MPA use in a node-negative population. Evidence for MPA use in postmenopausal node-positive breast cancer has been provided by the RxPONDER trial interim analysis but this relies on the absence of superiority in an analysis where >50% of events were unrelated to breast cancer. There is much uncertainty about MPA use for premenopausal patients. OPTIMA (Optimal Personalised Treatment of early breast cancer usIng Multi-parameter Analysis) (ISRCTN42400492) is a prospective international randomized controlled trial designed to validate MPAs as predictors of chemotherapy sensitivity in a largely node-positive breast cancer population. Methods: OPTIMA is a partially blinded study with an adaptive two-stage design. The trial recruits women and men age 40 or older with resected ER-positive, HER2-negative invasive breast cancer and up to 9 involved axillary lymph nodes. Randomization is to standard management (chemotherapy and endocrine therapy) or to MPA-directed treatment using the Prosigna (PAM50) test. Those with a Prosigna tumor Score (ROR_PT) >60 receive standard management whilst those with a low score (≤60) tumor are treated with endocrine therapy alone. Endocrine therapy for pre-menopausal women includes ovarian suppression for all participants unless they experience a chemotherapy-induced menopause. Adjuvant abemaciclib is permitted. The trial will be analyzed for (1) non-inferiority of recurrence according to randomization and (2) cost-effectiveness. The key secondary outcome is non-inferiority of recurrence for patients with low ROR_PT score tumors. The efficacy analyses will be performed Per Protocol using Invasive Breast Cancer Free Survival (IBCFS) as the primary outcome measure to limit the risk of a false non-inferiority conclusion. Recruitment of 4500 patients over 8 years will permit demonstration of up to 3% non-inferiority of test-directed treatment with at least 83% power, assuming 5-year IBCFS is 87% with standard management. An integrated qualitative recruitment study addresses challenges to consent and recruitment, building on experience from the feasibility study which found that a multidisciplinary approach is important for recruitment success. OPTIMA is strongly supported by a patient group which has helped design all patient documents and which is represented on the TMG. Results: The OPTIMA main trial opened in January 2017 and has continued to recruit throughout the COVID-19 pandemic. Overall recruitment as of 1 July 2022 was 2814 (2593 from UK, 221 from Norway). Patient characteristics are well balanced between the trial arms. Currently 95% of randomized participants are eligible for inclusion in the PP analysis. 66% of the MPA-directed arm participants have been allocated to endocrine therapy only. The test failure rate is < 1%. Conclusion: OPTIMA will provide robust unbiased evidence on test-directed chemotherapy safety for both postmenopausal and premenopausal women with 1-3 involved nodes as well as for patients with 4-9 involved nodes and for patients treated with abemaciclib. Funding: OPTIMA is funded by the UK NIHR HTA Programme (10/34/501) and in Norway by KLINBEFORSK and the Norwegian Cancer Society. Views expressed are those of the authors and not those of the HTA Programme, NIHR, NHS or the Department of Health. Trial Inquiries: OPTIMA@warwick.ac.uk Patient characteristics Citation Format: Robert Stein, Andreas Makris, Iain Macpherson, Luke Hughes-Davies, Andrea Marshall, Georgina Dotchin, David A. Cameron, Belinda E. Kiely, Caroline Wilson, Anne Armstrong, Helena M. Earl, Christopher J. Poole, Janice Tsang, Bjørn Naume, Daniel Rea, Hege Ohnstad, Peter S. Hall, Stuart A. McIntosh, Bethany Shinkins, Christopher McCabe, Adrienne Morgan, John MS Bartlett, Janet A. Dunn. OPTIMA, a prospective randomized trial to validate the clinical utility and cost-effectiveness of gene expression test-directed chemotherapy decisions in high clinical risk early breast cancer. [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr OT3-32-01.

Safety Climate Evaluation in Primary Health Care: A Cross-Sectional Study.

The perception of the existence of deficits in patient safety, the associated costs and the limitation of resources have made it essential to define improvement strategies. Important concepts have emerged, such as safety climate, which evaluates the perceptions of safety status held by professionals in relation to their organization. The aim of this study is to characterize the safety climate in primary health care (PHC) using the Safety Attitudes Questionnaire (SAQ)-Short Form 2006 PT and to assess associations between SAQ-Short Form 2006 PT scores and demographic and professional characteristics. A cross-sectional study was conducted in all public PHC units in the northern region of Portugal. Data were collected through an online questionnaire shared via institutional emails and by means of a snowball approach. Descriptive and inferential statistical analysis were performed. Statistical significance set at p ≤ 0.05. A total of 649/7427 (8.7%) responses were included in the analyses. The mean and median total SAQ-Short Form 2006 PT scores were 69.23 (SD = 15.73, range 22.22-100.00) and 71.53 [59.03; 79.86], respectively. This is the first study to assess the safety climate in PHC in Portugal. The median obtained total SAQ-Short Form 2006 PT score was 71.53 [59.03; 79.86], which is below the threshold of ≥75, indicating safety deficits.

Collateral Impact on Patients of Liver Diseases in the Second COVID-19 Wave: A Retrospective Cohort Study.

BackgroundThe second wave of the COVID-19 pandemic in India started in April 2021. This necessitated a change in focus from chronic ailments. This wave lasted till May 2021. Its impact on liver disease patients without COVID-19 infection has not been analyzed.MethodsRecords of liver disease patients from the Institute database admitted from April to May 2021 were compared with that from April to May 2019 i.e., prior to the pandemic. The primary outcome was a comparison of in-hospital mortality rates. Secondary outcomes were a comparison of 30 and 90-day readmission rates and liver transplantation rates.ResultsSeven hundred and seventy-one patients in April-May 2019 (group 1) and 545 patients in April-May 2021 (group 2) were analyzed. Patients in group 2 were sicker with higher PT (INR), urea, creatinine, CTP, and MELD score and low serum sodium, albumin, and platelet count with a higher prevalence of variceal bleed, hepatic encephalopathy, and acute kidney injury. There was higher mortality in group 2 (128/545; 23.5%) than group 1 (124/ 771;16.1%), OR 1.6, 95% CI 1.2 - 2.1, p<0.01. 30 day readmission rate was numerically higher in group1; 18.3% vs 16.9%, p=0.5. The 31-90 day readmission rate was higher in group 1; 29.4% vs 16.9%, p<0.01. There was no significant difference in the number of patients undergoing liver transplantation in two groups, 19 in group 1 and 14 in group 2 (p=0.90).ConclusionThe second wave of the COVID-19 pandemic had a significant collateral impact on liver disease patients even without causing infection in them. Patients were sicker at the time of admission with higher mortality.

Therapeutic Effect of Nanotitanium Oxide Combined with Exercise Rehabilitation Training on Wrist Joint Injury of Boxers

The rapid development of society promotes the rapid improvement of science and technology. On this basis, the development of nanotechnology has also made great achievements and has been applied to all walks of life. Among them, nanotitanium oxide provides favorable conditions for the medical treatment of various joint injuries. And sports rehabilitation training also plays an irreplaceable role in the treatment of joint injury, promoting the rapid recovery of joint injury. Boxing is a sport in which boxing gloves are worn for fighting. It has both amateur and professional competitions. The purpose of this paper is to study the therapeutic effect of nanotitanium oxide combined with sports rehabilitation training on the wrist joint injury of boxers. According to the therapeutic effect of the research, it can provide useful treatment basis for clinical treatment and help boxers recover wrist joint injury, so as to carry out boxing training later. The method adopted in this paper is as follows: first, the subjects were randomly divided into nanotitanium oxide combined with sports rehabilitation training group, nanotitanium oxide treatment group, sports rehabilitation training treatment group, and control group. Then, the subjects were tested with the score table, and the score data were recorded. Finally, chi‐square test was used to test the experimental results. In conclusion, through the research and comparison, it is found that nanotitanium oxide combined with sports rehabilitation training can reduce the pain of boxers’ wrist joint injury; after the treatment of wrist joint injury of boxers by nanotitanium oxide combined with sports rehabilitation training, the pain score decreased, and the daily function was improved; the PT score before the experiment was 15%, and the peak torque score after the experiment was 26%. The Pt/BW score was 22% before the experiment and 37% after the experiment. This reflects the strength of wrist muscle contraction, judging that the stability of wrist joint is enhanced after the experiment; nanotitanium oxide combined with exercise rehabilitation training can increase the sensitivity of wrist joint after the treatment of boxer wrist joint injury.

Recovery from Coronavirus Disease 2019 among Older Adults in Post-Acute Skilled Nursing Facilities

ObjectivesTo examine functional outcomes of post-acute care for coronavirus disease 2019 (COVID-19) in skilled nursing facilities (SNFs). DesignRetrospective cohort. Setting and ParticipantsSeventy-three community-dwelling adults ≥65 years of age admitted for post-acute care from 2 SNFs from March 15, 2020, to May 30, 2020. Measure(s)COVID-19 status was determined from chart review. Frailty was measured with a deficit accumulation frailty index (FI), categorized into nonfrail, mild frailty, and moderate-to-severe frailty. The primary outcome was community discharge. Secondary outcomes included change in functional status from SNF admission to discharge, based on modified Barthel index (mBI) and continuous functional scale scored by physical (PT) and occupational therapists (OT). ResultsAmong 73 admissions (31 COVID-19 negative, 42 COVID-19 positive), mean [standard deviation (SD)] age was 83.5 (8.8) and 42 (57.5%) were female, with mean FI of 0.31 (0.01) with no differences by COVID-19 status. The mean length of SNF stay for rehabilitation was 21.2 days (SD 11.1) for COVID-19 negative with 20 (64.5%) patients discharged to community, compared to 23.0 (SD 12.2) and 31 (73.8%) among patients who tested positive for COVID-19. Among those discharged to the community, all groups improved in mBI, PT, and OT score. Those with moderate-to-severe frailty (FI >0.35) had lower mBI scores on discharge [92.0 (6.7) not frail, 81.0 (15.4) mild frailty, 48.6 (20.4) moderate-to-severe frailty; P = .002], lower PT scores on discharge [54.2 (3.9) nonfrail, 51.5 (8.0) mild frailty, 37.1 (9.7) moderate-to-severe frailty; P = .002], and lower OT score on discharge [52.9 (3.2) nonfrail, 45.8 (9.4) mild frailty, 32.4 (7.4) moderate or worse frailty; P = .001]. Conclusions and ImplicationsOlder adults admitted to a SNF for post-acute care with COVID-19 had community discharge rates and functional improvement comparable to a COVID-19 negative group. However, those who are frailer at admission tended to have lower function at discharge.

Additional factors to corelate with a more than 30% NIHSS score improvement in patients 7\u2009days after fibrinolytic and/or endovascular treatment for ischemic stroke

BackgroundOur objective was to find which additional factors can influence the favorable result in stroke patients after receiving fibrinolytic and/or endovascular treatment, quantified as a more than 30% improvement of the NIHSS score at 7 days.MethodsThis is a retrospective study to find factors that could influence a favorable evolution of patients with stroke that underwent fibrinolytic and or thrombectomy using the NIHSS score changes. At the admission in the hospital, blood glucose, blood count, coagulation time, INR, aPTT, PT, platelet count, NIHSS questionnaire and ASPECTS score were collected. NIHSS was assessed at the admission, after 1 h, after 2 h, after 24 h and after 7 days.ResultsAs compared to the initial evaluation, at 7 days after admission 59% (72) of patients have improved with more than 30% the NIHSS. Higher levels of systolic blood pressure, glycemia and lower ASPECTS score at admission were observed in non-achievers. The value of INR contributed to model: for every unit increase of INR, the chance of better outcome decreases by 90,1%. High glycemia has also a negative impact: for every unit increase, the chance of better outcome decreases by 24%. Higher initial ASPECTS score is associated with better outcomes: each point increase of ASPECTS score at initial evaluation, increases the chance of better outcome by 154.2%.ConclusionMales, older age, diabetes, and hyperglycemia correlate with a worse outcome after cerebral stroke regardless of the benefit yielded fibrinolytic and/or thrombectomy therapy. In this study, patients with the above-mentioned factors did not improve more than 30% of baseline NIHSS score from admission to the 7th day.

Predictive and Prognostic Value of Ascitic Fluid Mannose Binding Lectin in Patients with Spontaneous Bacterial Peritonitis.

Spontaneous bacterial peritonitis is a common bacterial infection of ascitic fluid, mainly in ascites due to liver cirrhosis. Mannose-binding lectin (MBL) can activate phagocytosis and the complement system. Spontaneous bacterial peritonitis was detected to be higher in MBL deficiency. This study aimed to assess ascitic fluid MBL in liver cirrhosis and spontaneous bacterial peritonitis. Ninety patients with cirrhotic ascites were included. Forty five of them had SBP. Child- Pugh score, Model for End Stage Liver Disease (MELD) and its update (uMELD) scores were used to assess the severity of liver cirrhosis. Ascitic fluid samples were obtained for differentiation of leucocytic count, estimation of albumin, protein, glucose, and serum-ascitic albumin gradient. Ascitic fluid levels of MBL were measured for all patients. SBP was documented if polymorphonuclear leucocytic count ≥250/mm in ascitic fluid. Ascitic fluid MBL level was significantly lower in patients with SBP. MBL had a significant negative correlation with ascitic total leukocytic count (TLC), also with serum creatinine, bilirubin, PT, INR and MELD score among SBP patients. However, it had a significant positive correlation with ascitic protein and with platelets. According to multivariate analysis, fever, TLC, platelets, creatinine, MBL, glucose and polymorphs were independent predictors for SBP development. Ascitic fluid MBL could be a good predictive and prognostic marker in patients with cirrhosis and spontaneous bacterial peritonitis.

Development and Validation of a Scoring System, Based on Genetic and Clinical Factors, to Determine Risk of Steatohepatitis in Asian Patients with Nonalcoholic Fatty Liver Disease

There are no biomarkers of nonalcoholic steatohepatitis (NASH) that are ready for routine clinical use. We investigated whether an analysis of PNPLA3 and TM6SF2 genotypes (rs738409 and rs58542926) can be used to identify patients with nonalcoholic fatty liver disease (NAFLD), with and without diabetes, who also have NASH. We collected data from the Boramae registry in Korea on 453 patients with biopsy-proven NAFLD with sufficient clinical data for calculating scores. Patients enrolled from February 2014 through March 2016 were assigned to cohort 1 (n= 302; discovery cohort) and patients enrolled thereafter were assigned to cohort 2 (n= 151; validation cohort). DNA samples were obtained from all participants and analyzed for the PNPLA3 rs738409 C>G, TM6SF2 rs58542926 C>T, SREBF2 rs133291 C>T, MBOAT7-TMC4 rs641738 C>T, and HSD17B13 rs72613567 adenine insertion (A-INS) polymorphisms. We used multivariable logistic regression analyses with stepwise backward selection to build a model to determine patients' risk for NASH (NASH PT) using the genotype and clinical data from cohort 1 and tested its accuracy in cohort 2. We used the receiver operating characteristic (ROC) curve to compare the diagnostic performances of the NASH PT and the NASH scoring systems. We developed a NASH PT scoring system based on PNPLA3 and TM6SF2 genotypes, diabetes status, insulin resistance, and levels of aspartate aminotransferase and high-sensitivity C-reactive protein. NASH PT scores identified patients with NASH with an area under the ROC (AUROC) of 0.859 (95%CI, 0.817-0.901) in cohort 1. In cohort 2, NASH PT scores identified patients with NASH with an AUROC of 0.787 (95% CI, 0.715-0.860), which was significantly higher than the AUROC of the NASH score (AUROC, 0.729; 95% CI, 0.647-0.812; P= .007). The AUROC of the NASH PT score for detecting NASH in patients with NAFLD with diabetes was 0.835 (95% CI, 0.776-0.895) and in patients without diabetes was 0.809 (95% CI, 0.757-0.861). The negative predictive value of the NASH PT score <-0.785 for NASH in patients with NAFLD with diabetes reached 0.905. We developed a scoring system, based on polymorphisms in PNPLA3 and TM6SF2 and clinical factors that identifies patients with NAFLD, with or without diabetes, who have NASH, with an AUROC value of 0.787. This system might help clinicians better identify NAFLD patients at risk for NASH.

Serum Cholinesterase Level as a Biomarker in Detecting Liver Injury in Patients with Chronic Hepatitis C

Background: hepatitis C virus can cause both acute and chronic hepatitis. The acute process is self-limited, rarely causes hepatic failure and usually leads to chronic infection. Chronic HCV infection often follows a progressive course over many years and can ultimately result in cirrhosis, HCC and the need for liver transplantation. Objective: the aim of this study is to evaluate serum cholinesterase (CHE) level as a biomarker for detecting liver damage in patients with chronic hepatitis C. Patients and Methods: the current study was carried out on 50 subjects selected from the outpatient's clinic of Internal Medicine Department of Sayed Galal Hospital, Al-Azhar University and admitted to the internal department. The study was performed in the period between July-2014 to July -2019. Results: Sensitivity of cholinesterase is 100%, its specificity is 100% and its accuracy is 100%, in predicting liver injury in patients with chronic hepatitis C. Cholinesterase is positively correlated with Hb, platelets and albumin. Cholinesterase is negatively correlated with ALT, AST and ALP, total & direct bilirubin, PT, INR, urea, creatinine and AFP. There is significant increase of cholinesterase among compensated compared with decompensated cirrhotic patients. There is significant decrease of cholinesterase among compensated cirrhotic patients compared with controls. There is significant decrease of cholinesterase among decompensated cirrhotic patients compared with controls. Conclusion: cholinesterase is an excellent biomarker of cirrhosis with good sensitivity and specificity. Cholinesterase shows good correlation with albumin, PT, INR and Child-Puch score. Cholinesterase distinguishes decompensated cirrhosis from compensated cirrhosis well.

Serum Cholinesterase Level as a Biomarker in Detecting Liver Injury in Patients with Chronic Hepatitis C

Background: hepatitis C virus can cause both acute and chronic hepatitis. The acute process is self-limited, rarely causes hepatic failure and usually leads to chronic infection. Chronic HCV infection often follows a progressive course over many years and can ultimately result in cirrhosis, HCC and the need for liver transplantation. Objective: the aim of this study is to evaluate serum cholinesterase (CHE) level as a biomarker for detecting liver damage in patients with chronic hepatitis C. Patients and Methods: the current study was carried out on 50 subjects selected from the outpatient's clinic of Internal Medicine Department of Sayed Galal Hospital, Al-Azhar University and admitted to the internal department. The study was performed in the period between July-2014 to July -2019. Results: Sensitivity of cholinesterase is 100%, its specificity is 100% and its accuracy is 100%, in predicting liver injury in patients with chronic hepatitis C. Cholinesterase is positively correlated with Hb, platelets and albumin. Cholinesterase is negatively correlated with ALT, AST and ALP, total & direct bilirubin, PT, INR, urea, creatinine and AFP. There is significant increase of cholinesterase among compensated compared with decompensated cirrhotic patients. There is significant decrease of cholinesterase among compensated cirrhotic patients compared with controls. There is significant decrease of cholinesterase among decompensated cirrhotic patients compared with controls. Conclusion: cholinesterase is an excellent biomarker of cirrhosis with good sensitivity and specificity. Cholinesterase shows good correlation with albumin, PT, INR and Child-Puch score. Cholinesterase distinguishes decompensated cirrhosis from compensated cirrhosis well.

Assessment of Spasticity by a Pendulum Test in SCI Patients Who Exercise FES Cycling or Receive Only Conventional Therapy.

Increased muscle tone and exaggerated tendon reflexes characterize most of the individuals after a spinal cord injury (SCI). We estimated seven parameters from the pendulum test and used them to compare with the Ashworth modified scale of spasticity grades in three populations (retrospective study) to assess their spasticity. Three ASIA B SCI patients who exercised on a stationary FES bicycle formed group F, six ASIA B SCI patients who received only conventional therapy were in the group C, and six healthy individuals constituted the group H. The parameters from the pendulum test were used to form a single measure, termed the PT score, for each subject. The pendulum test parameters show differences between the F and C groups, but not between the F and H groups, however, statistical significance was limited due to the small study size. Results show a small deviation from the mean for all parameters in the F group and substantial deviations from the mean for the parameters in the C group. PT scores show significant differences between the F and C groups and the C and H groups and no differences between the F and C groups. The correlation between the PT score and Ashworth score was 0.88.

Role of Portal Hypertension in Prediction of Bacterial Infection in Decompensated Cirrhosis

Background: Bacterial infection in cirrhotic patients is a fatal complication. The high incidence of bacterial infections in those patients may be related to several alterations in the defensive mechanisms against infections and increased intestinal permeability with bacterial translocation. Aim: To evaluate the role of portal hypertension (PH) in predicting the occurrence of bacterial infections in decompensated cirrhosis. Patients and Methods: In this retrospective cohort study, 99 patients—56 males and 43 females, with decompensated liver cirrhosis were included. Diagnosis of liver cirrhosis was based on clinical, laboratory and ultrasonographic examinations. Patients were classified according to the presence of bacterial infection into patients with infection—Group 1, and those without infection—Group 2. Laboratory, abdominal US and upper endoscopic data for all patients were collected. Logistic regression analysis was done to detect the independent factors for prediction of bacterial infection. Results: The mean age of patients was 50.5 ± 14.2 years. Bacterial infection was found in 41 patients (41.4%) and no infection in 58 patients (58.6%). Infected patients showed statistically significant higher values in the level of bilirubin, PT and Child-Pugh score (P value = 0.000) and lower values in the level of albumin, total serum protein and PC than those without infection (P value = 0.006, 0.000 and 0.000 respectively). Portal vein diameter (PVD) and splenic diameter (SD) showed statistically significant higher values in infected patients than in those without infection (P value = 0.028 and 0.000 respectively), also infection was more significantly prevalent in patients with varices than those without varices (P value = 0.000). The independent predictors for bacterial infection were: the age, total serum bilirubin, serum albumin, PT, PC, child score, PVD, SD and the presence of varices. Conclusion: Presence of varices (as a complication of PH) is an independent risk factor for the development of bacterial infection in decompensated cirrhotic patients and reduction of PH by any way could decrease this fatal complication.

615 EARLY USE OF TIPS DECREASES REBLEEDING AND IMPROVES THE SURVIVAL IN CIRRHOTIC PATIENTS OF EVL ULCER BLEEDING: A PROSPECTIVE STUDY

S 21 ANNUAL CONFERENCE —2013 C rrh o is & C o m p ica tio n s EARLY USE OF TIPS DECREASES REBLEEDING AND IMPROVES THE SURVIVAL IN CIRRHOTIC PATIENTS OF EVL ULCER BLEEDING: A PROSPECTIVE STUDY Ashok Choudhury, Hitendra Garg, Amar Mukund, Manoj Kumar, R. Kumar, Shiv K. Sarin Institute of Liver and Biliary Sciences, New Delhi, India Background: Endoscopic variceal ligation (EVL) is the recommended method to manage esophageal variceal bleeding with lower variceal ulceration and rebleeding rates compared to sclerotherapy. A proportion of patients develops EVL induced ulcers and present with massive bleeding. In these cases, endotherapy is difficult and often unsuccessful and definitive methods, such as TIPS need to be evaluated. Aim: Determine the effectiveness of reduction in portal pressure by polytetrafluoroethylene-covered transjugular stenting (TIPS) for band-induced esophageal ulcer bleeding. Method: Following admission within 24 hours, consecutive patients with cirrhosis and EVL induced bleeding ulcers were prospectively treated using standard therapy (endoscopy and vasoactive drugs; Group 1, n=17) or standard therapy plus TIPS (Group 2, n=22). Primary endpoint was survival at 6 wks. Secondary end-points were early and late rebleeding. Results: Total 488 cirrhotic patients who underwent EVL from 2010-11, 36 (7%) (Median age 42 (range 32-72), 90% males) developed bleeding EVL ulcer. These patients were enrolled and offered either of the two treatments. Baseline parameters including age, presence of ascites, HE, HRS, platelets, PT (INR), HVPG, Child and MELD score were similar in both the groups. After follow-up of 6 wks, 10 patients (62%) in group 1 and 5 (25%) in group 2 died (P<0.05). The incidence of failure to control bleed/early rebleed was seen in 9 patients (56%) in group1 and in 1(5%) in group 2 (P <0.05). Similarly, the incidence of late rebleeding was seen in 5 patients (45.4%) in group 1 while in 1(5%) in group2 (P <0.05). The median time to death was 2.5 (0.5-12) days and 13 (2-21) days in the two groups (P <0.05). Conclusion: Around 7% patients develop life threatening EVL induced ulcer bleeding. Portal pressure reduction with the TIPS is significantly superior in the control of bleeding, preventing rebleeding and reduction in mortality. Corresponding author. Hitendra Garg. E-mail: drhitendragarg@yahoo.com

Early use of Tips Decreases Rebleeding and Improves the Survival in Cirrhotic Patients of EVL Ulcer Bleeding: A Prospective Study

Background: Endoscopic variceal ligation (EVL) is the recommended method to manage esophageal variceal bleeding with lower variceal ulceration and rebleeding rates compared to sclerotherapy. A proportion of patients develops EVL induced ulcers and present with massive bleeding. In these cases, endotherapy is difficult and often unsuccessful and definitive methods, such as TIPS need to be evaluated. Aim: Determine the effectiveness of reduction in portal pressure by polytetrafluoroethylene-covered transjugular stenting (TIPS) for band-induced esophageal ulcer bleeding. Method: Following admission within 24 hours, consecutive patients with cirrhosis and EVL induced bleeding ulcers were prospectively treated using standard therapy (endoscopy and vasoactive drugs; Group 1, n=17) or standard therapy plus TIPS (Group 2, n=22). Primary end-point was survival at 6 wks. Secondary end-points were early and late rebleeding. Results: Total 488 cirrhotic patients who underwent EVL from 2010-11, 36 (7%) (Median age 42 (range 32-72), 90% males) developed bleeding EVL ulcer. These patients were enrolled and offered either of the two treatments. Baseline parameters including age, presence of ascites, HE, HRS, platelets, PT (INR), HVPG, Child and MELD score were similar in both the groups. After follow-up of 6 wks, 10 patients (62%) in group 1 and 5 (25%) in group 2 died (P<0.05). The incidence of failure to control bleed/early rebleed was seen in 9 patients (56%) in group1 and in 1(5%) in group 2 (P <0.05). Similarly, the incidence of late rebleeding was seen in 5 patients (45.4%) in group 1 while in 1(5%) in group2 (P <0.05). The median time to death was 2.5 (0.5-12) days and 13 (2-21) days in the two groups (P <0.05). Conclusion: Around 7% patients develop life threatening EVL induced ulcer bleeding. Portal pressure reduction with the TIPS is significantly superior in the control of bleeding, preventing rebleeding and reduction in mortality.

Efficacy of lamivudine on acute-on-chronic liver failure in patients with chronic hepatitis B

To observe the therapeutic effects of lamivudine treatment in patients with early- to mid-stage hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF). Clinical data of 73 hospitalized patients with HBV-ACLF were retrospectively analyzed. Prothrombin time (PT, active coagulation), HBV DNA, and model for end-stage liver disease (MELD) score data from treatment weeks 4, 8, 24, and 48 were collected and analyzed using the statistical t-test. During the treatment duration, the complete virologic response rates were 57.5% (42/73) at 4 weeks, 71.0% (44/62) at 8 weeks, 83.1% (49/59) at 24 weeks, and 86.5% (45/52) at 48 weeks. The partial virologic response rates were 30.1% (22/73) at 4 weeks, 25.8% (16/62) at 8 weeks, 17.0% (10/59) at 24 weeks, and 13.5% (7/52) at 48 weeks. At week 48, the survival rate was 71.2% (52/73) and the probability of survival was higher in the complete virological response rate (VRR) group than in the partial VRR group [45/73 (61.6%) vs. 7/73 (30.1%), respectively; P = 0.000]. In addition, there were significant improvements in the serum normalization rate of HBV DNA, alanine aminotransferase, aspartate aminotransferase, albumin, total bilirubin, PT and MELD score in surviving patients compared to baseline (P less than 0.05) and in the complete VRR group compared to the partial VRR group (P less than 0.05). Antiviral therapy using lamivudine may be an effective therapeutic option for patients with HBV-ACLF.

Expression of COX-2 and PPARg in the livers of patients with acute on chronic HBV-related liver failure and their relationship with clinic parameters

To study the expressions of cyclooxygenase-2 (COX-2) and Peroxisome proliferator-activated receptor gamma (PPARg) in liver of patients with hepatitis B virus (HBV) related acute-on-chronic liver failure (ACLF) and their correlation with clinical parameters. 35 patients with ACLF, 35 patients with HBV related chronic liver failure (CLF), 27 patients with chronic hepatitis B(CHB) and 15 normal control were enrolled to study the expressions of COX-2 and PPARg in the liver tissues by immunohistochemical staining, and to analyze the correlation of the COX-2 and PPARg levels in liver tissues with clinical parameters. COX-2 was distinctly expressed in the cytoplasm of the hepatocytes, but PPARg was mostly expressed in the nuclei of the hepatocytes and also could be seen in the cytoplasm. The expressions of COX-2 in the liver of ACLF, CLF and CHB groups increased significantly as compared with NC group (z = -5.18, -4.50, -5.32, P is less than 0.01). The levels of COX-2 in ACLF livers also increased evidently as compared with CLF groups (z = -1.98, P is less than 0.05). The expression levels of PPARg in ACLF liver tissues were much higher than the other three groups, and statistical significances existed between ACLF group and the other two groups (CLF, NC groups) (z = -2.62, -4.28, P is less than 0.01). In ACLF group, the expression of COX-2 correlated with MELD score (r = 0.337, P is less than 0.05) and the expression of PPARg correlated with HBV DNA load (r = 0.348, P is less than 0.05). Clinical data showed that the levels of AST, TBil, CHOL, PT, INR, FIB and MELD score in ACLF group were significantly different from that in CLF, CHB and NC groups. COX-2 expressed in liver may be a marker to reflect the degree of inflammation and injury of liver tissue. The PPARg expression of liver could be increased during chronic HBV infection and may be a protective mechanism against liver injury.

Risk factors of postoperative delirium following liver transplantation.

Postoperative delirium (POD) after liver transplantation is a serious complication. This study investigated the incidence and the risk factors of POD in liver transplantation recipients. Three hundred and sixty eight adult recipients who had undergone liver transplantation were included. We reviewed medical records and the POD was determined by either psychiatric consultation or established diagnostic criteria. Recipients were divided into two groups according to the occurrence of POD: POD group (n = 150) and non-POD group (n = 218), and risk factors were assessed. One hundred fifty (40.8%) of the 368 recipients developed POD after liver transplantation. History of alcohol consumption and alcoholic liver disease, history of hepatic encephalopathy, preoperative mental status changes, ventilator care, dialysis, hypotension, and ICU care were significantly higher in the POD group. In the preoperative laboratory test, sodium was lower while bilirubin, PT (INR) and MELD score were higher in the POD group. Postoperative variables including dialysis, ventilator care duration, ICU stay, hospital stay, glucose and ammonia were significantly higher in the POD group. Three variables were identified as independent predictors of POD in a multiple regression analysis: history of alcohol consumption (odds ratio, 2.04; 95% confidence interval [CI], 1.12-3.72; P = 0.02), history of hepatic encephalopathy (odds ratio, 2.54; 95% CI, 1.46-4.41, P<0.01), and MELD score (odds ratio, 1.03; 95% CI, 1.00-1.06; P = 0.02). The development of POD and related morbidity and mortality would be reduced if we identified the recipients with risk factors preoperatively and applied early intervention.

In vitro transcription of the TATAA-less mouse thymidylate synthase promoter: multiple transcription start points and evidence for bidirectionality

The mouse thymidylate synthase (TS) promoter ( pTS) lacks a TATAA box and an initiator element, and has multiple transcription start points ( tsp) located across a 90-bp region. We have developed an in vitro transcription system for pTS using circular templates and nuclear extracts from HeLa cells or mouse 3T6 fibroblasts. The amount of RNA synthesized and the locations of the tsp were determined by S1 nuclease protection assays. The transcription system reproduced the complex pattern of in vivo tsp, except that the downstream tsp were used preferentially. The reaction temperature, concentrations of DNA template and MgCl 2, and incubation time were optimized. The pTS core region contains binding sites for the Sp1 and Ets transcription factors. Inactivation of the Spl-binding element led to a twofold reduction in transcription and a preferential use of upstream tsp. Inactivation of the Ets-binding element, which reduced promoter activity tenfold in vivo, had only a minor effect in vitro. Addition of a strong initiator element introduced a new tsp, but did not eliminate the complex tsp pattern. To determine if pTS had bidirectional promoter activity, the promoter was inverted and analyzed for transcriptional activity. The inverted promoter was found to initiate transcription at multiple tsp and had approximately the same strength as the normal pTS.