Early Outcome of On-pump Versus Off-pump Elective Surgical Revascularization in Patients with Prior ST-Segment Elevation Myocardial Infarction.

Coronary artery bypass graft surgery (CABG) is a proven treatment for coronary artery disease. History of a ST-elevation myocardial infarction (STEMI) is considered an independent risk factor for CABG irrespective of timing for an emergency or elective surgery. Patients with STEMI are candidates for both On-pump and Off-pump CABG procedures. This paper discusses the possible best option for elective surgical revascularization in patients with prior STEMI. This prospective clinical trial of 60 eligible patients with prior STEMI was conducted in a Tertiary Care Hospital from April 2018 to March 2019. Among them, 30 patients underwent off-pump (Group A) and 30 patients underwent on-pump (Group B) CABG procedures. Outcomes between both groups were observed from surgery to 1 month postoperatively. Data was analysed by the software statistical program for social science (SPSS 25.0 Inc). The surgery was successful in both groups of patients. Differences were observed by mean number of grafts per patient (2.77±0.43 vs. 3.10±0.71) and duration of operation (4.41±0.35 hours vs. 5.71±0.48 hours). An improvement in Left Ventricular Ejection Fraction (LVEF %) was observed in both groups postoperatively (17.98% vs. 10.98%) and the postoperative LVEF% at different time points were found statistically significant (p<0.05) over preoperative LVEF%. Multivariable stepwise logistic regression analysis correlated on-pump CABG with prolonged need for ionotropic support, need for blood transfusion, longer hospital stay and less improvement in LVEF%. The study supports the Off-pump CABG as a better surgical option over on-pump CABG in patients with prior STEMI.

Relationship of Conduction Defects and In-Hospital Outcome after Acute ST Segment Elevation Myocardial Infarction.

The presence of conduction defects complicating acute myocardial infarction (MI) is relatively frequent and is associated with increased short and long term mortality. Thrombolytic therapy has been established to reduce the mortality in acute MI, however its role in reducing the incidence of conduction defects is less clearly defined. Morbidity and mortality associated with conduction defects also remain unchanged. This study was aimed to assess the correlation between conduction defects and adverse in-hospital outcome of patients with acute ST segment elevation MI. This cross sectional descriptive type of observational study was conducted among 100 purposively selected patients with acute ST segment elevation MI in the coronary care unit (CCU) of Mymensingh Medical College Hospital, Bangladesh from June 2012 to March 2013. The patients were divided into two groups depending on the presence or absence of conduction defects namely Group A- 40 patients with conduction defects and Group B- 60 patients without conduction defects. Highest number of the patients (36.0%) was in the age group of 45-55 years. In case of inferior MI, age groups 45-55 years and 55-65 years had equal number of patients (30.4%). Only 2.0% patients were in age group of 75-85 years and this group had only inferior MI. Total number of female patients were 16(16.0%). Female patients had more inferior MI (17.4%) than anterior MI (15.9%). Number of MI patients was slightly more in inferior MI (46.0%) than anterior MI (44.0%). Group B had equal number of patients in both anterior and inferior MI. Conduction defects were more common in inferior MI (43.5%) than anterior MI (40.9%). Atrio-ventricular conduction defects were more common in inferior MI whereas intra-ventricular conduction defects were more common in anterior MI. Complete heart block (CHB) was more prevalent in inferior MI. Complications were more common in Group A (65.0%) than Group B (18.3%). In terms of complications the difference between two groups were significant (p<0.001). Group A showed higher rate of mortality (20.0%) than Group B (3.3%). In cases of anterior MI difference in mortality between Group A and Group B was highly significant (p<0.001). Conduction defects in the setting of acute MI are a common finding. Atrio-ventricular conduction defects occur more frequently in inferior MI whereas intra-ventricular conduction defects were more frequently encountered in anterior MI. Patients with conduction defects had more complications than those without conduction defects. Presence of conduction defects significantly increases the mortality of patients with anterior MI.

Association of Aortic Valve Sclerosis with Angiographic Severity of Coronary Artery Disease in Patients with Acute Coronary Syndrome, Aged ≤65 Years.

Aortic valve sclerosis (AVS) represents a degenerative process that progresses with advancing age. The study was intended to find out the association between aortic valve sclerosis and the severity of CAD in patient's age ≤65 years with acute coronary syndrome. This cross-sectional analytical study was carried out in the department of cardiology, National Institute of Cardiovascular Diseases (NICVD), Dhaka, Bangladesh during a period of October 2017 to September 2018. A total of 140 Acute coronary syndrome (ACS) patients undergoing coronary angiogram during index hospitalization were included in the study. Study patients were divided into two groups on the basis of echocardiographic presence or absence of Aortic valve sclerosis (AVS), with 70 patients in each group. Group I was patients with aortic valve sclerosis and Group II was patients without aortic valve sclerosis. All patients underwent transthoracic echocardiography before they underwent coronary angiography on different days. Severity of CAD was determined by Gensini score and Vessel score. Association of traditional risk factors (smoking habit, hypertension, diabetes mellitus, dyslipidaemia and family history of CAD) with severity of CAD was investigated. Coronary angiography showed that AVS group had a higher positive rate of CAD (82.9% vs. 54.3%, p<0.001) and incidence rate of triple vessel CAD (40% vs. 14.3%, p<0.001) than non-AVS group. Gensini score had higher in AVS group than non AVS group (37.9±27.8 vs. 12.5±14.2; p<0.001). Multivariate analysis showed that AVS (p=0.01) and age (p=0.04) were independent predictors of the presence of significant coronary artery disease. The study concluded that echocardiographically detected AVS is an independent predictor of coronary artery disease severity. There is positive correlation between severity of AVS and severity of CAD in patient's age ≤65 years with ACS.

Association of Diastolic Dysfunction with Angiographic Severity of Coronary Artery Disease in patients with Non-ST Elevation Myocardial Infarction.

In recent years, diastolic dysfunction is an evolving context. Presence of left ventricular diastolic dysfunction (LVDD) indicates a poor prognosis in patients with an ACS and chronic coronary artery diseases. This study evaluated the association of LVDD and angiographic severity of CAD in patients with non-ST elevation myocardial infarction (NSTEMI). This cross-sectional analytical study was carried out in National Institute of Cardiovascular Diseases, Dhaka, Bangladesh, during the period of April 2017 to March 2018. A total of 120 NSTEMI patients undergoing coronary angiogram (CAG) during index hospitalization were included in the study. All patients underwent transthoracic echocardiography before they underwent CAG on different days. Presence (Group I, n=65) and absence of LVDD (Group II, n=55) was established by echocardiography. Severity of CAD was assessed by Vessel score and Leaman score. Association of traditional risk factors (smoking habit, hypertension, diabetes mellitus, dyslipidemia and family history of CAD) with severity of CAD was investigated. Vessel score showed coronary artery obstruction (CAO) was present in 62(95.4%) patients in Group I and 35(63.6%) patients in Group II, single vessel was involved in 17(27.4%) patients while multi vessel in 45(72.6%) patients was found in Group I. On the contrary 27(77.1%) single vessel patients and 8(22.9%) multi vessel patients were found in Group II. Positive Leaman score was significantly higher in Group I, 62(95.4%) than that of Group II, 35(63.6%) which is statistically significant (p<0.001). This study showed a positive correlation between LVDD and CAD severity in terms of vessel score and Leamanscore. This study also demonstrates that the severity of vessel score and Leaman score was higher in the higher grade of diastolic dysfunction. The present study concludes that LVDD is associated with angiographically severe CAD in patients with NSTEMI.

Association of Echocardiographic Epicardial Fat Thickness with the Angiographic Severity of Coronary Artery Disease in Patients with Acute Coronary Syndrome.

Estimation of visceral adipose tissue is important as it carries high cardiometabolic risk and several methods are available as its surrogate. Epicardial fat thickness (EFT) is a direct measure of visceral fat rather than anthropometric measurements. EFT can be accurately measured by two-dimensional (2D) echocardiography. It tends to be higher in patients with Acute Coronary Syndrome (ACS). The present study was intended to find out the association between echocardiographic EFT and severity of Coronary Artery Disease (CAD) in patients with ACS. This cross-sectional observational study was carried out in the department of cardiology, National Institute of Cardiovascular Diseases, Dhaka, Bangladesh from October 2017 to September 2018. Sampling technique was purposive sampling. Comparison between groups was done by unpaired-t test & dichotomous variables were compared by chi-square test. A total of 164 patients was enrolled in the study, prospectively examined EFT on echocardiography and patients were divided into 2 groups, Group I patients with EFT >4.65mm and Group II patients with EFT ≤4.65mm. Coronary angiograms were analyzed for the extent and severity of CAD using Gensini score. The mean EFT (mm) was found 6.1±1.0 in Group I and 3.5±0.7 in Group II (p<0.001). Patients with a higher EFT were associated with a high Gensini score (Group I vs. Group II, 50.3±24.1 vs. 21.9±20.0; p<0.001). Multivariate analysis showed that EFT (OR 6.07, p<0.001) and smoking (OR 2.66, p=0.03) were independent factors affecting significant coronary artery stenosis. By ROC curve analysis, EFT >4.65mm predicated the presence of significant coronary stenosis by 76.1% sensitivity and 69.9% specificity. EFT measured using Transthoracic echocardiography (TTE) significantly correlates with the severity of CAD. It is sensitive, easily available, and cost-effective and assists in the risk stratification and may be an additional marker on classical risk factors for CAD.

Prevalence and types of genetic polymorphisms of CYP2C19 and their effects on platelet aggregation inhibition by clopidogrel.

OBJECTIVE: The current study was conducted to determine the distribution of genetic polymorphisms in CYP2C19 in Iraqi patients and their role in inter-individual variability of clopidogrel efficacy. PATIENTS AND METHODS: A prospective controlled study was done on 100 patients under high risk of cardiovascular diseases who started clopidogrel prophylactic therapy. Polymerase chain reaction-restriction fragment length polymorphism method was used to determine the existence of the CYP2C19 gene mutation. Vasodilator-stimulated phosphoprotein (VASP) index baseline besides one-month post-therapy was analyzed by dual-color flow cytometry analysis. RESULTS: Eight gene mutations of CYP2C19 were found (*1/*1), (*1/*2), (*1/*3), (*1/*8), (*1/*17), (*2/*2), (*2/*4), and (*3/*3) with higher prevalent CYP2C19*1 gene. Homozygous CYP2C19*1 allele was shown to be the rapid metabolizer comparing to the heterozygous CYP2C19*1 allele, whereas, CYP2C19*2 and CYP2C19*3 were resistant alleles and were present in 28% of patients. The analysis of VASP phosphorylation produces accurate inter-individual response variability in platelets inhibition by antiplatelet drugs. CONCLUSIONS: In vitro gene analysis and VASP index improve the clinical outcome of a patient candidate to clopidogrel as prophylaxis in cardiovascular events.

Study on Precipitating Factor of Chronic Hepatic Encephalopathy.

Hepatic encephalopathy (HE) is a neuro-psychiatric manifestation of chronic liver disease causing significant morbidity and mortality worldwide. Though the exact mechanism is unknown but it is well accepted that various precipitating factors are involved in hepatic encephalopathy. Aim of the study was explore the precipitating factors of chronic hepatic encephalopathy. This cross sectional descriptive study was conducted in the Department of Medicine and Department of Hepatology, Mymensingh Medical College Hospital, Mymensingh, Bangladesh during the period from April 2016 to October 2016. One hundred patients with hepatic encephalopathy fulfilling the inclusion and exclusion criteria were enrolled. Inclusion criteria were designed for all diagnosed cases of hepatic encephalopathy associated with cirrhosis of liver aged 18 years or above irrespective of sex. Patients with acute fulminant hepatitis and non-cirrhotic hepatic encephalopathy were excluded. The result of the study was mean age of hepatic encephalopathy was 52.81±8.15 years and 94.0% patients were above 40 years. Male (66.0%) were predominant over female (34.0%). HBsAg and Anti HCV were positive in 49.0% and 11.0% patients respectively. Stage of hepatic encephalopathy was stage-I in 8.0%, stage-II in 37.0%, stage-III in 39.0% and stage-IV in 16.0% patients. Changes of biochemical parameters were low haemoglobin level (70.0%), raised total count of leukocyte (25.0%), low platelet count (68.0%), low serum albumin (98.0%) raised prothrombin time (60.0%), low serum sodium (34.0%) and low serum potassium (63.0%). The recoded precipitating factors were gastrointestinal bleeding (14.0%), constipation (37.0%), hyponatremia (34.0%), hypokalemia (28.0%) infections (20.0%), use of diruretics (8.0%), use of sedatives (4.0%) and excess intake of protein (6.0%). While precipitating factor was absent in 11.0% of cases. In conclusion there are different factors which play a key role in precipitating hepatic encephalopathy but electrolytes imbalance, constipation, infections, Upper GI bleed, diuretics are the most common precipitating factors.

Demography and Symptom Profile of Tetanus: A Cross-sectional Observation in an Infectious Disease Hospital of Bangladesh.

Tetanus is a potentially preventable neurological infectious disorder with paucity of literature in Bangladesh. We aimed to see the demography and symptom profile of tetanus cases managed at the Infectious disease Hospital Sylhet. This hospital based cross-sectional descriptive study was conducted within the time period of January to December 2012 among 50 consecutive admitted patients in the Infectious Disease Hospital, Sylhet, Bangladesh who were diagnosed as a case of tetanus and fulfilling the inclusion criteria and exclusion criteria. Neonatal tetanus was considered as exclusion criteria and clinical diagnosis of tetanus was considered as the tetanus. Data were collected purposively with pretested predesigned questionnaire. Data were processed manually and analyzed with the help of SPSS Version 16.0. The mean±SD age was 33.00±16.8 years, ranging from 10 to 70 years. Among the 50 respondents, 72.0% were male, 50% from lower class, 34% were students and 30.0% had their educational status of primary level, 60.0% from rural social background. Trismus was found in 98.0% of the cases, rigidity in 96.0% cases, body ache in 94.0% cases, dysphagia in 92.0% cases, neck pain in 78.0% cases, dysarthria in 92.0% cases, reflex spasm in 66.0% cases, opisthotonus in 46.0% cases and urinary retention in 26.0% cases. In this study rural male people with lower socioeconomic status individuals were mostly affected with trismus, rigidity, body ache and dysphagia symptoms.

Gender Difference of Common Risk Factors and in Hospital Outcome of Acute Ischaemic Stroke.

This was an observational study with cross-sectional comparison of risk factors between sexes in the distribution of common risk factors and in hospital outcome of acute ischaemic stroke with the purpose of developing optimal strategies for the prevention and care of this disease. This study was conducted in the Department of Medicine and Department of Neurology, Sylhet MAG Osmani Medical College Hospital, Sylhet, Bangladesh from March 2013 to August 2013. Patients were divided in Group A- male patients with acute ischaemic stroke (n=47) and Group B- female patients with acute ischaemic stroke (n=47), were included according to inclusion and exclusion criteria. Male were more frequently diabetic [19(40.4%) vs. 10(21.3%), p=0.044] and smoker [41(87.2%) vs. 18 (38.3%); p<0.001] than that of female. Female were older [67.4±8.9 years vs. 62.2±8.1 years; p<0.05]; more frequent hypertensive [36(76.6%) vs. 26(55.3%); p=0.030] than that of male but no gender differences in atrial fibrillation, ischemic heart disease, dyslipidaemia. In-hospital functional outcome (p=0.039) was significantly better in male than that of female patients with acute ischaemic stroke. Characterization of risk factors for acute ischaemic stroke in both sexes may aid in developing prevention strategies to reduce stroke incidence.

Comparative Study between the Use of Multidose Standard Cardioplegia and Long Acting Del Nido Cardioplegia during Intracardiac Repair for Tetralogy of Fallot in Pediatric Patients.

Pediatric myocardium is unique from mature myocardium; thus, the use of adult cardioplegia for pediatric cardiac operations may provide suboptimal myocardial protection. It is found that children undergoing heart surgery show evidence of less myocardial damage when del Nido cardioplegia is used instead of a standard cardioplegic solution. Del Nido cardioplegia solution provides a depolarized hyperkalaemic arrest lasting up to 60 minutes, reduces spontaneous and inducible activity during arrest, and prevents hyper contraction during early reperfusion. In this single blind randomized trial, a total of 60 patients underwent intra cardiac repair for TOF in National Institute of Cardiovascular Diseases, Dhaka, Bangladesh from July 2014 to January 2016 fulfilling inclusion and exclusion criteria. They were randomly assigned in two groups- 30 patients in Del Nido group (Group A) and 30 patients in standard group (Group B). Comparison between groups was done by Chi square test and Student's test. All data were analyzed by SPSS 20.0 for windows. P value less than 0.05 was considered as significant. There was statistically significant difference among the patients in terms of mean total initial cardioplegia volume, mean number of additional dose, mean additional dose amount, mean cross clamp time, mean CPB time (331.67±188.07 vs. 458.67±226.62, p=0.022; 0.13±0.35 vs. 1.27±0.89, p=0.000; 23.33±60.76 vs. 336.83±259.6, p=0.000; 45.10±10.35 vs. 59.23±23.21, p=0.003; 89.30±15.73 vs. 111.10±29.23, p=0.001 respectively). Mean post operative serum troponin I level at arrival in ICU and after 24 hours between two groups were statistically significantly different (55.60±32.91 vs. 83.5±58.99; p=0.024 and 13.01±5.84 vs. 18.16±9.51; p=0.014 respectively). The mean ventilation duration, mean ICU stay were also statistically significant. This study showed that cardiac arrest with Del Nido cardioplegia during intra cardiac repair for TOF was associated with improved myocardial protection over standard cardioplegia in terms of reduced CPB and cross clamp times, lower total volume of cardioplegia.

Non-invasively Measured Carotid Artery Intima-Medial Thickness May Be a More Useful Marker of Coronary Artery Disease in Diabetic than Non-Diabetic Patients.

Carotid intima-medial thickness has long been proposed as a surrogate marker of atherosclerotic vascular disease in other vascular beds, most notably the coronary arteries with its practical implications. This observational study aimed at exploring the relationship of a hypothetical stronger relationship of carotid intima-medial thickness with coronary artery disease in diabetic patients than non-diabetic counterparts. Thirty diabetic patients and 74 non-diabetic patients who were referred for coronary angiogram in the Departments of Cardiology Bangabandhu Sheikh Mujib Medical University and Combined Military Hospital, Dhaka Cantonment, Bangladesh from January, 2002 and December, 2003 were studied. Carotid ultrasound was done to determine intima-medial thickness and coronary angiogram to detect coronary artery lesions. Background demographic data and cardiovascular risk factors were determined. Of the 30 diabetic patients 24 subjects had CAD. Twenty two of these 24 patients showed increased carotid IMT. None of the patients without CAD had shown carotid artery intima-medial thickening (sensitivity 91% specificity 100%). In contrast, in the non-diabetic group 44 patients out of 63 with CAD showed increased carotid artery IMT. Four of the 11 non-diabetic patients without CAD showed positive carotid ultrasound study results (sensitivity 70%, specificity 63%). This study showed a strong association of coronary artery disease with carotid intima-medial thickness in diabetic patients compared to non-diabetic subjects. This finding may be applicable for Bangladeshi diabetic population. This surrogate marker of coronary artery disease can be useful in the management of diabetes as regards their prevention of coronary artery disease. The practical and clinical implications of these findings might be the pioneer study in diabetic subjects and need to be further determined in a larger community level study.

Wnt5a induces ROR1 to associate with 14-3-3ζ for enhanced chemotaxis and proliferation of chronic lymphocytic leukemia cells.

Wnt5a can activate Rho GTPases in chronic lymphocytic leukemia (CLL) cells by inducing the recruitment of ARHGEF2 to ROR1. Mass spectrometry on immune precipitates of Wnt5a-activated ROR1 identified 14-3-3ζ, which was confirmed by co-immunoprecipitation. The capacity of Wnt5a to induce ROR1 to complex with 14-3-3ζ could be blocked in CLL cells by treatment with cirmtuzumab, a humanized mAb targeting ROR1. Silencing 14-3-3ζ via small interfering RNA impaired the capacity of Wnt5a to: (1) induce recruitment of ARHGEF2 to ROR1, (2) enhance in vitro exchange activity of ARHGEF2 and (3) induce activation of RhoA and Rac1 in CLL cells. Furthermore, CRISPR/Cas9 deletion of 14-3-3ζ in ROR1-negative CLL cell-line MEC1, and in MEC1 cells transfected to express ROR1 (MEC1-ROR1), demonstrated that 14-3-3ζ was necessary for the growth/engraftment advantage of MEC1-ROR1 over MEC1 cells. We identified a binding motif (RSPS857SAS) in ROR1 for 14-3-3ζ. Site-directed mutagenesis of ROR1 demonstrated that serine-857 was required for the recruitment of 14-3-3ζ and ARHGEF2 to ROR1, and activation of RhoA and Rac1. Collectively, this study reveals that 14-3-3ζ plays a critical role in Wnt5a/ROR1 signaling, leading to enhanced CLL migration and proliferation.

Wnt5a induces ROR1 to complex with HS1 to enhance migration of chronic lymphocytic leukemia cells.

ROR1 (receptor tyrosine kinase-like orphan receptor 1) is a conserved, oncoembryonic surface antigen expressed in chronic lymphocytic leukemia (CLL). We found that ROR1 associates with hematopoietic-lineage-cell-specific protein 1 (HS1) in freshly isolated CLL cells or in CLL cells cultured with exogenous Wnt5a. Wnt5a also induced HS1 tyrosine phosphorylation, recruitment of ARHGEF1, activation of RhoA and enhanced chemokine-directed migration; such effects could be inhibited by cirmtuzumab, a humanized anti-ROR1 mAb. We generated truncated forms of ROR1 and found its extracellular cysteine-rich domain or kringle domain was necessary for Wnt5a-induced HS1 phosphorylation. Moreover, the cytoplamic, and more specifically the proline-rich domain (PRD), of ROR1 was required for it to associate with HS1 and allow for F-actin polymerization in response to Wnt5a. Accordingly, we introduced single amino acid substitutions of proline (P) to alanine (A) in the ROR1 PRD at positions 784, 808, 826, 841 or 850 in potential SH3-binding motifs. In contrast to wild-type ROR1, or other ROR1P→︀A mutants, ROR1P(841)A had impaired capacity to recruit HS1 and ARHGEF1 to ROR1 in response to Wnt5a. Moreover, Wnt5a could not induce cells expressing ROR1P(841)A to phosphorylate HS1 or activate ARHGEF1, and was unable to enhance CLL-cell motility. Collectively, these studies indicate HS1 plays an important role in ROR1-dependent Wnt5a-enhanced chemokine-directed leukemia-cell migration.

A 42-year-old man with huge abdominal mass.

Patients presenting with abdominal lump is a common clinical finding in our medical practice. Most of the cases can be diagnosed without much difficulty. But sometimes it can be difficult to diagnose the cause of the lump. Here we are presenting a 42-year-old man who visited his physician in Bangabandhu Sheikh Mujib Medical University with huge abdominal lump. Initially it was diagnosed as hepatocellular carcinoma (HCC). Later it turned out to be case of adrenocortical carcinoma (ACC). Problems related to diagnosis and management is also discussed.

A case of acute intermittent porphyria.

Acute intermittent porphyria (AIP) is a rare autosomal dominant hereditary metabolic disorder having protean manifestations. The clinical presentations of abdominal pain, peripheral neuropathy and changes in mental status are the classic triad of an acute attack. A 15-year old girl was admitted in the medicine department of Sylhet MAG Osmani Medical College with the complaints of recurrent abdominal pain, convulsions and weakness of lower limbs. She presented with a combination of medical and neuropsychiatric symptoms suggestive of a case of AIP. The clinical presentation and the presence of porphyrins in urine confirmed the diagnosis of AIP. AIP can be life-threatening, so an accurate diagnosis and proper management are highly important.

Gastrointestinal manifestations as initial presenting features in a 40 years old woman with systemic lupus erythematosus.

Gastrointestinal (GI) symptoms are common in patients with systemic lupus erythematosus (SLE). These symptoms can be due to primary GI disorders like peptic ulcer disease, pancreatitis or intestinal obstruction. But they can be due to SLE itself or complications of treatment of SLE. In this case report, we describe a 40 years old woman who presented initially with GI complaints. Later she was diagnosed as a case of SLE with chronic intestinal pseudo-obstruction (CIPO). The problems related to diagnosis and management is also discussed.

Outcomes after implementing a tailored endoscopic step-up approach to walled-off necrosis in acute pancreatitis.

BACKGROUND: The aim of the study was to compare the outcomes of patients with pancreatic or peripancreatic walled-off necrosis by endoscopy using the conventional approach versus an algorithmic approach based on the collection size, location and stepwise response to intervention. METHODS: This was an observational before-after study of consecutive patients managed over two time intervals. In the initial period (2004-2009) symptomatic patients with walled-off necrosis underwent conventional single transmural drainage with placement of two stents and a nasocystic catheter, followed by direct endoscopic necrosectomy, if required. In the later period (2010-2013) an algorithmic approach was adopted based on size and extent of the walled-off necrosis and stepwise response to intervention. The main outcome was treatment success, defined as a reduction in walled-off necrosis size to 2 cm or less on CT after 8 weeks. RESULTS: Forty-seven patients were treated in the first interval and 53 in the second. There was no difference in patient demographics, clinical or walled-off necrosis characteristics and laboratory parameters between the groups, apart from a higher proportion of women and Caucasians in the later period. The treatment success rate was higher for the algorithmic approach compared with conventional treatment (91 versus 60 per cent respectively; P < 0·001). On multivariable logistic regression, management based on the algorithm was the only predictor of treatment success (odds ratio 6·51, 95 per cent c.i. 2·19 to 19·37; P = 0·001). CONCLUSION: An algorithmic approach to pancreatic and peripancreatic walled-off necrosis, based on the collection size, location and stepwise response to intervention, resulted in an improved rate of treatment success compared with conventional endoscopic management.

Solving fuzzy fractional differential equations using Zadeh's extension principle.

We study a fuzzy fractional differential equation (FFDE) and present its solution using Zadeh's extension principle. The proposed study extends the case of fuzzy differential equations of integer order. We also propose a numerical method to approximate the solution of FFDEs. To solve nonlinear problems, the proposed numerical method is then incorporated into an unconstrained optimisation technique. Several numerical examples are provided.

NAMPT overexpression in prostate cancer and its contribution to tumor cell survival and stress response.

Nicotinamide phosphoribosyltransferase (NAMPT) is a rate-limiting enzyme in regenerating nicotinamide adenine dinucleotide (NAD(+)) from nicotinamide in mammals. NAMPT has crucial roles for many cellular functions by regulating NAD(+)-dependent SIRT1 deacetylase. However, roles of NAMPT in cancer are poorly defined. In this study, we show that NAMPT is prominently overexpressed in human prostate cancer cells along with SIRT1. Elevation of NAMPT expression occurs early for the prostate neoplasia. Inhibition of NAMPT significantly suppresses cell growth in culture, soft agar colony formation, cell invasion and growth of xenografted prostate cancer cells in mice. NAMPT knockdown sensitizes prostate cancer cells to oxidative stress caused by H(2)O(2) or chemotherapeutic treatment. Overexpression of NAMPT increases prostate cancer cell resistance to oxidative stress, which is partially blocked by SIRT1 knockdown. We demonstrate that in addition to modulating SIRT1 functions, the NAMPT inhibition reduces forkhead box, class 'O' (FOXO)3a protein expression and its downstream anti-oxidant genes catalase and manganese superoxide dismutase. Our results suggest important roles of concomitant upregulation of NAMPT and SIRT1 along with increased FOXO3a protein level for prostate carcinogenesis and their contribution to oxidative stress resistance of prostate cancer cells. These findings may have implications for exploring the NAMPT pathway for prostate cancer prevention and treatment.

Molecular characterization of apoptosis induced by CARF silencing in human cancer cells.

Collaborator of ARF (CARF) was cloned as an ARF-interacting protein and shown to regulate the p53-p21(WAF1)-HDM2 pathway, which is central to tumor suppression via senescence and apoptosis. We had previously reported that CARF inhibition in cancer cells led to polyploidy and caspase-dependent apoptosis, however, the mechanisms governing this phenomenon remained unknown. Thus, we examined various cell death and survival pathways including the mitochondrial stress, ataxia telangiectasia mutated (ATM)-ATR, Ras-MAP kinase and retinoblastoma cascades. We found that CARF is a pleiotropic regulator with widespread effects; its suppression affected all investigated pathways. Most remarkably, it protected the cells against genotoxicity; CARF knockdown elicited DNA damage response as evidenced by increased levels of phosphorylated ATM and γH2AX, leading to induction of mitotic arrest and eventual apoptosis. We also show that the CARF-silencing-induced apoptosis in vitro translates to in vivo. In a human tumor xenograft mouse model, treatment of developing tumors with short hairpin RNA (shRNA) against CARF via an adenovirus carrier induced complete suppression of tumor growth, suggesting that CARF shRNA is a strong candidate for an anticancer reagent. We demonstrate that CARF has a vital role in genome preservation and tumor suppression and CARF siRNA is an effective novel cancer therapeutic agent.