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Purpose Minimal hepatic encephalopathy (MHE) is an important complication of chronic liver disease (CLD); however, MHE burden in patients with primary biliary cholangitis (PBC) has not been determined yet. Therefore, our study aimed to assess the prevalence of MHE in a typical cohort of middle-aged, patients with PBC suspicion of liver fibrosis and to investigate the relationship between MHE, basic laboratory tests and the stage of liver fibrosis. Patients and methods Fifty-one patients (38 with PBC and 13 controls), were prospectively enrolled. Portosystemic Encephalopathy-Syndrome test was used to diagnose MHE. Elastography point qualification (ElastPQ) and non-invasive markers (APRI and FIB-4) were used to assess liver fibrosis. The severity of CLD was assessed using the Model of End-Stage Liver Disease (MELD) and Child-Pugh score. Results MHE was diagnosed in 9 patients (24.3%) with PBC and none in the control group. As many as 44.4% of the patients with MHE had neither advanced fibrosis nor cirrhosis, as demonstrated using non-invasive markers of liver fibrosis or ElastPQ. The MELD score was the only predictor of MHE with cut-off value 8.5 [AUC ​= ​0.753, CI95% ​= ​0.569 to 0.938)] with sensitivity of 56%, specificity of 85% and accuracy of the test of 78%. Non-invasive markers of liver fibrosis and ElastPQ did not predict MHE. Conclusions MHE may occur in PBC despite no evidence of advanced liver fibrosis or cirrhosis. The slightly elevated MELD score may indicate a substantially increased risk of MHE in patients with PBC.

Introduction Proton pump inhibitors therapy success in the treatment of gastroesophageal reflux disease (GERD) is a difficult task because the extent of mucosal damage has no relation with the severity of the symptoms. Aim To establish the efficacy of pantoprazole treatment in patients with erosive reflux disease (ERD) and in those with non-erosive reflux disease (NERD), by assessing symptom relief and quality of life. Treatment duration and adverse events associated with pantoprazole treatment were analysed. Material and methods This meta-analysis was based on three multicentre, prospective, open-label, phase IV trials conducted in Slovenia, Poland, and the Russian Federation. In total, 252 patients with GERD were included and treated with pantoprazole 40 mg once daily for 4 or 8 weeks, depending on the fulfilment of predefined healing criteria. Symptoms were assessed by patients on a scale from 0 to 3 and the quality of life on a rating scale from 1 to 10. Results Forty-five percent of patients fulfilled the healing criteria after 4 weeks of treatment, and 70% of patients after 8 weeks of treatment. Patients who failed to reach the healing criteria reported significant reduction of symptoms severity. The response to 8-week treatment was significantly higher in patients with ERD (76%) when compared to patients with NERD (64%). Discontinuation of treatment after 4 weeks was not associated with worsening of symptoms and did not affect quality of life. Pantoprazole treatment was associated with improvement of symptoms and the quality of life of GERD patients over 8 weeks of treatment and showed that GERD patients with persisting symptoms benefit from prolonging treatment to 8 weeks. Treatment with pantoprazole 40 mg was very well tolerated - more than 90% of patients were without adverse events throughout the whole study and only 4 patients discontinued the treatment due to adverse events related to pantoprazole treatment. Conclusions Pantoprazole 40 mg was associated with complete relief of GERD-related symptoms in the majority of patients with ERD and NERD. Furthermore, the severity of symptoms was significantly reduced in patients without complete relief of symptoms. Pantoprazole also continuously improved the quality of life of GERD patients over 8 weeks of treatment and was very well tolerated throughout the whole study. Therefore, this meta-analysis suggests that pantoprazole 40 mg once daily is an effective and well-tolerated choice for providing symptom relief of patients with GERD.

Pancreatic ductal adenocarcinoma is one of the deadliest human neoplasms. Despite the development of new surgical and adjuvant therapies, the prognosis remains very poor, with the overall survival rate not exceeding 9%. There is now increasing evidence that the human microbiome, which is involved in many physiological functions, including the regulation of metabolic processes and the modulation of the immune system, is possibly linked to pancreatic oncogenesis. However, the exact mechanisms of action are poorly understood. Our review summarizes the current understanding of how the microbiome affects pancreatic cancer development and progression. We discuss potential pathways of microbe translocation to the pancreas, as well as the mechanism of their action. We describe the role of the microbiome as a potential marker of pancreatic cancer diagnosis, progression, and survival. Finally, we discuss the possibilities of modifying the microbiome to improve treatment effectiveness for this deadly disease.

Background Cigarette smoke (CS) exerts protective effect against ulcerative colitis. The mechanism of this phenomenon remains unknown. One of the possible explanation by which CS exerts its anti-inflammatory action is modulation of immune system. Therefore, the aim of the study was to evaluate the effect of CS on the course of inflammation and subpopulations of lymphocytes in the blood and colon in mice with dextran sulfate sodium (DSS)-induced colitis. Methods C57BL6/cmdb mice were exposed to CS for 4 weeks. Colitis was induced with 3.5% DSS given for 10 days. Severity of colitis was determined by disease activity index (DAI), body weight changes, and macro- and microscopic characteristics of inflammation. Peripheral subpopulations of lymphocytes were assessed by flow cytometry (blood) or immunohistochemistry (colonic tissue). Results Mice treated with 3.5% DSS developed severe colitis with significantly decreased body weight, increased DAI, and macroscopic and histological features of colonic inflammation. These findings were diminished after concomitant exposure to CS. Mice exposed to DSS alone demonstrated significantly decreased percentage of total CD4+ cells (73.1 vs. 52%, p = 0.0007), accompanied by increase of CD8+ cells (18.4 vs. 39.5%, p = 0.0001). Concomitant CS exposure reversed inappropriate CD4+/CD8+ ratio both in the blood and colon and significantly increased B cell presence in the colon. Conclusions Our study has demonstrated that CS exposure decreases severity of DSS-induced colitis. This phenomenon was accompanied by changes in CD4/CD8 ratio and B cell level in the peripheral blood and colon. These mechanisms may be responsible for protective effect of smoking in ulcerative colitis. Electronic supplementary material The online version of this article (doi:10.1007/s00384-017-2882-9) contains supplementary material, which is available to authorized users.

Background Endoscopic techniques have become the first-line therapy in bariatric surgery-related complications such as leaks and fistulas. We performed a systematic review and meta-analysis on the effectiveness of self-expandable stents, clipping, and tissue sealants in closing of post-bariatric surgery leak/fistula. Methods A systematic literature search of the Medline/Scopus databases was performed to identify full-text articles published up to February 2019 on the use of self-expandable stents, clipping, or tissue sealants as primary endoscopic strategies used for leak/fistula closure. Meta-analysis of studies reporting stents was performed with the PRISMA guidelines. Results Data concerning the efficacy of self-expanding stents in the treatment of leaks/fistulas after bariatric surgery were extracted from 40 studies (493 patients). The overall proportion of successful leak/fistula closure was 92% (95% CI, 90–95%). The overall proportion of stent migration was 23% (95% CI, 19–28%). Seventeen papers (98 patients) reported the use of clipping: the over-the-scope clips (OTSC) system was used in 85 patients with a successful closure rate of 67.1% and a few complications (migration, stenosis, tear). The successful fistula/leak closure using other than OTSC types was achieved in 69.2% of patients. In 10 case series (63 patients), fibrin glue alone was used with a 92.8–100% success rate of fistula closure that usually required repeated sessions at scheduled intervals. The complications of fibrin glue applications were reported in only one study and included pain and fever in 12.5% of patients. Conclusions Endoscopic techniques are effective for management of post-bariatric leaks and fistulas in properly selected patients.

Objective: The study aimed at assessing the effect of thrombocytopenia and platelet function abnormalities on the occurrence of variceal bleeding in patients with cirrhosis.Methods: The results of ...

Background and Aims Therapeutic endoscopy plays a critical role in the management of upper GI (UGI) postsurgical leaks. Data are scarce regarding clinical success and safety. Our aim was to evaluate the effectiveness of endoscopic therapy for UGI postsurgical leaks and associated adverse events (AEs) and to identify factors associated with successful endoscopic therapy and AE occurrence. Methods This was a retrospective, multicenter, international study of all patients who underwent endoscopic therapy for UGI postsurgical leaks between 2014 and 2019. Results Two hundred six patients were included. Index surgery most often performed was sleeve gastrectomy (39.3%), followed by gastrectomy (23.8%) and esophagectomy (22.8%). The median time between index surgery and commencement of endoscopic therapy was 16 days. Endoscopic closure was achieved in 80.1% of patients after a median follow-up of 52 days (interquartile range, 33-81.3). Seven hundred seventy-five therapeutic endoscopies were performed. Multimodal therapy was needed in 40.8% of patients. The cumulative success of leak resolution reached a plateau between the third and fourth techniques (approximately 70%-80%); this was achieved after 125 days of endoscopic therapy. Smaller leak initial diameters, hospitalization in a general ward, hemodynamic stability, absence of respiratory failure, previous gastrectomy, fewer numbers of therapeutic endoscopies performed, shorter length of stay, and shorter times to leak closure were associated with better outcomes. Overall, 102 endoscopic therapy–related AEs occurred in 81 patients (39.3%), with most managed conservatively or endoscopically. Leak-related mortality rate was 12.4%. Conclusions Multimodal therapeutic endoscopy, despite being time-consuming and requiring multiple procedures, allows leak closure in a significant proportion of patients with a low rate of severe AEs.

Objective We aimed to identify the best method of omeprazole (OME) application with respect to intragastric pH, cytochrome P450 2C19 (CYP2C19) genotype and phenotype. Methods The patients with non-variceal upper gastrointestinal bleeding (NVUGIB) were prospectively enrolled. After the achievement of endoscopic hemostasis, the patients were randomized to 40-mg intravenous (i.v.) OME bolus injection every 12 h or 8-mg/h continuous i.v. infusion for 72 h after an 80-mg i.v. OME bolus administration. The intragastric pH was recorded for 72 h. The CYP2C19 variant alleles (*2, *3, *17) were analyzed and the serum concentrations of OME and 5-hydroxyomeprazole (5-OH OME) were determined. Results Altogether 41 Caucasians (18 in the OME infusion [OI] group and 23 in the OME bolus [OB] group) were analyzed. The median percentage of time with an intragastric pH > 4.0 was higher in the infusion group than in the OB group over 48 h (100% vs 96.6%, P = 0.009) and 72 h (100% vs 87.6%, P = 0.006), and that at an intragastric pH >6.0 was higher in the OI group than the OB group over 72 h (97.9% vs 63.5%, P = 0.04). Helicobacter pylori infection was correlated with the fastest increase in intragastric pH, especially in the OI group. In both groups, CYP2C19 genotypes (*1/*1, *1/*17, *17/*17) had no essential effect on intragastric pH. Conclusions In patients with NVUGIB, OME i.v. bolus followed by continuous infusion is more effective than OME i.v. bolus every 12 h in maintaining higher intragastric pH, regardless of CYP2C19 genetic polymorphisms. H. pylori infection accelerates the initial elevation of intragastric pH.

Aim We aimed to assess the relationship between procoagulant imbalance and the occurrence of variceal bleeding in patients with liver cirrhosis. Methods We compared the results of chromogenic assay for the functional evaluation of the Protein C anticoagulant pathway (ThromboPath®), thromboelastometry and the levels of factor VII, VIII, and antithrombin in two groups of cirrhotic patients: Group 1 (n = 25) — patients with moderate or large esophageal or gastric varices, who had never experienced acute gastrointestinal bleeding and Group 2 (n = 24) — patients with a history of variceal bleeding. Results Despite the differences in MELD score and the results of basic laboratory tests indicating more severe cirrhosis and suggesting a greater risk of bleeding in Group 2, the results of thromboelastometry did not differ significantly between groups. The ThromboPath® test results [ThP B: 67.8 ± 13.4 versus 59.09 ± 12.4%, p = 0.023] and factor VII level [69.04 ± 24.16 vs 53.54 ± 25.06, p = 0.032] confirmed greater plasma procoagulant activity in Group 1 compared to Group 2. However, there were no statistically significant differences in thrombin generation after activation of the protein C. Plasma of patients in Group 2 was more resistant to anticoagulation with protein C compared to Group 1 (PICI%: 65.58 ± 7.24 versus 55.64 ± 13.07%, p = 0.001). Conclusion The results of our study confirm the lack of influence of coagulation disorders on the occurrence of variceal bleeding. Moreover, the results of ThromboPath® assay indicate hypercoagulability in patients with a history of variceal bleeding and more severe liver cirrhosis, compared to patients who have never bled.

The authors used cluster analysis of data from cardiovascular domains associated with exercise intolerance to help define prognostic phenotypes of patients with heart failure with preserved ejection fraction (HFpEF).Resting and postexercise echocardiography was performed in 177 patients with HFpEF and 51 asymptomatic control subjects sharing a common clinical profile. Patterns of features that determine exercise capacity were sought from automated hierarchical clustering of left ventricular (LV) diastolic and systolic function, left atrial function, right ventricular function, ventricular-arterial coupling, chronotropic reserve and myocardial fibrosis.Automated clustering separated a distinct subgroup characterized by a relatively isolated impairment of LV systolic reserve. The clinical factors identified by this process were used to define two phenotypes of patients with symptomatic HFpEF: those with reduced chronotropic and/or diastolic reserve (abnormal CR/DR; n = 137) and those with preserved heart rate reserve and exertional E/e' ratio 14 (normal CR/DR; n = 40). Change in global LV strain rate from rest to exercise was similar in patients with abnormal CR/DR (0.16 ± 0.18 secDiminished LV systolic reserve may represent the major identifiable cardiac functional abnormality associated with exercise intolerance in some patients with HFpEF. Despite significant functional limitation, these patients are characterized by a better prognosis than subjects with HFpEF with more physiologic abnormalities.

Introduction The presence of esophageal varices in liver cirrhosis indicates clinically significant portal hypertension (PH), that results from structural and dynamic changes in the liver and systemic circulation including the activation of several fibrotic and inflammatory pathways. We assessed if interleukin-18 (IL-18) and transforming growth factor-β1 (TGF-β1) serum levels can be used as PH markers and reflect its severity. Material and methods IL-18 and TGF-β1 peripheral blood levels were analyzed in 83 cirrhotic patients with esophageal varices compared to healthy individuals, in relation to MELD and Child-Pugh scores, laboratory and Doppler ultrasound parameters, and non-selective beta-blocker therapy (NSBB). Results IL-18 concentration was significantly higher in cirrhotic patients, while TGF-β1 concentration was lower than in controls. MELD score correlated positively with IL-18 levels and negatively with TGF-β1 levels. IL-18 levels correlated positively with bilirubin, INR, ALT and AST levels, and negatively with albumin levels and erythrocyte count. TGF-β1 levels correlated positively with platelet count, leukocyte, and erythrocyte count, and negatively with bilirubin levels and prothrombin time. Moreover, significant correlations were found: between IL and 18 levels and portal, mesenteric superior, and splenic vein velocity, and between TGF-β1 levels and splenic vein diameter and spleen size. In a subgroup of patients, IL-18 levels significantly decreased after NSBB. Conclusion The observed imbalance of peripheral IL-18 and TGF-β1 levels indicates clinically significant PH associated with the presence of esophageal varices in cirrhosis. The correlation of IL-18 levels with liver failure indicators and decrease with NSBB suggest an important role of IL-18 in disease progression and its potential use as noninvasive test for PH assessment.

Background Beneficial clinical effects of weight reduction following bariatric therapies is not fully understood and maybe related to the complex interactions between leptin, adiponectin, visfatin, omentin, and ghrelin. The aim of study was to investigate their timeline changes associated with weight reduction and their profile in relation to the type of treatment and its efficacy. Methods Circulating hormones levels were analyzed before and after endoscopic and surgical procedures in 67 obese patients and compared to non-obese healthy controls. Results Obese patients had higher leptin levels and lower levels of adiponectin, visfatin, omentin, and ghrelin than non-obese controls. During the consecutive follow-up visits after treatment, there was a gradual decrease in leptin levels and an increase in adiponectin levels to the levels observed in non-obese. At 50–54 weeks, the ghrelin levels were lower and the levels of adiponectin and visfatin, but not omentin, were higher compared to their baseline values. BMI correlated with ghrelin and leptin levels. The percentage of total weight loss correlated positively with adiponectin levels and negatively with leptin levels. Patients with adequate weight loss had a significantly lower leptin concentration than those with treatment failure. There were timeline variations in hormone levels between endoscopic and bariatric therapies, however there were no significant differences in the median their concentration at 50–54 weeks after therapy. Conclusion Our study supports observations that weight loss itself, rather than the procedure type, is responsible for hormonal variation. The leptin levels reflect the best the body weight changes after bariatric therapies.

In this paper, we present a new brain diagnostic method based on a computer aided multispectral ultrasound diagnostics method (CAMUD). We explored the standard values of the relative time of flight (RIT), as well as the attenuation, ATN, of multispectral longitudinal ultrasound waves propagated non-invasively through the brains of a standard Caucasian volunteer population across different ages and genders. For the interpretation of the volunteers health questionnaire and ultrasound data we explored various clustering and classification algorithms, such as PCA and ANOVA. We showed that the RIT and ATN values provide very good estimators of possible physiological changes in the brain tissue and can differentiate the possible high-risk groups obtained by other groups and methods (Russo et al. [1] ; Lloyd-Jones et al. [2] ; Medscape [3] ). Special attention should be given to the subgroup which included almost 39% of the volunteers. Respondents in this group have a significantly increased minimum ATN value (see Classification Trees). These values are strongly correlated with the identified risk of stroke factors being: age, increased alcohol consumption, cases of heart disease and stroke in the family as already shown by Rusco and as incorporated into Lloyd-Jones et al., “Heart Disease and Stroke Statistics – 2009 Update”, by the American Heart Association (AHA) and American Stroke Association (ASA), as updated recently in the 2015 “Stroke Prevention Guidelines”.

Objective The invasive measurement of hepatic venous pressure gradient is the recommended method for the assessment of portal hypertension. We assessed if the mediators that regulate portal hypertension may be used as noninvasive markers of portal hypertension and liver insufficiency. Materials and methods We explored in prospective, observational study the concentration of endothelin-1, nitric oxide, and transforming growth factor-β1/2 in peripheral and hepatic venous blood; their relationship with the values of portal hypertension and liver insufficiency; and their level changes 4–6 months after non-selective beta-blocker therapy in cirrhotic patients with non-bleeding esophageal varices. Results (1) Cirrhotics have significantly increased peripheral endothelin 1 and decreased transforming growth factor-β1 levels; (2) peripheral levels of all factors correlated significantly with their hepatic levels; (3) after therapy, peripheral endothelin-1 levels significantly increased, but transforming growth factor-β2 levels decreased and were lower in patients with pressure gradient value normalization; (4) before and after therapy, peripheral and hepatic endothelin-1, transforming growth factor-β1/2 levels correlated significantly with liver failure indicators (laboratory parameters, Child-Pough and MELD scores) and pressure gradient values. Conclusions Peripheral endothelin-1 and transforming growth factor-β1 levels, which strongly correlate with their hepatic levels, reflect the stage of portal hypertension and liver insufficiency in cirrhosis.

Barrett's esophagus (BE), a complication of gastroesophageal reflux disease, is associated with an increased risk of esophageal cancer. Mitogen-activated protein kinases may play an important role in the pathogenesis of this process. We aimed to evaluate mitogen-activated protein kinases activity in esophageal mucosa of patients with BE and find possible relationship between reflux type and BE. Twenty-four patients (mean age: 59 years) with gastroesophageal reflux disease symptoms and endoscopically suspected esophageal metaplasia (ESEM) were prospectively enrolled for testing by a multichannel intraluminal impedance monitoring along with a Bilitec 2000. Endoscopic biopsies were taken from methylene blue-positive pit patterns (sites suggesting specialized intestinal metaplasia [SIM]), from 2 cm above the Z-line and from cardial parts of the stomach. The biopsies were analyzed for extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), p38 activity by Western blot. Seventeen ESEMs had histologically proven metaplasia: eight patients had SIM and nine had gastric-type epithelia (GE). Biliary reflux was more evident in SIM (P = 0.019) but not in GE (P = 0.019); non-biliary reflux was typical for GE (P = 0.005) but not for SIM (P = 0.04). Strong activations of ERK and p38 were found predominantly in SIM, but not in normal esophageal mucosa (NE) (P = 0.01 and P < 0.001 respectively). Strong signals for active JNK and p38 were detected in GE, but not in NE (P = 0.006 and P = 0.02 respectively). ERK activity was significantly higher than p38 activity in ESEM patients only with GE (P = 0.02). The strong activation of ERK, but not JNK is indicative of SIM. The presence of bile in gastroesophageal refluxate is predisposing to SIM, but not to GE in esophageal mucosa.

The exact time of initiation of total enteral nutrition (TEN) in severe acute pancreatitis (SAP) and its influence on the disease outcome are not well known.An analysis of 197 cases with predicted SAP allocated to: group A (n = 97), early TEN (started within the first 48 hours after admission to hospital); and group B (n = 100), delayed TEN (started after 48 hours).Infection of necrosis/fluid collections occurred in 4 patients in group A and 18 patients in group B (P0.05). Respiratory failure and transfer to intensive care unit occurred more frequently in group B than in group A (15 vs 5 and 15 vs 3 patients; P0.05). Multiple-organ failure was observed in 9 patients in group A and 16 patients in group B (P0.05). Seven patients in group A and 11 patients in group B underwent surgery (P0.05). All 9 reported deaths occurred in group B (P0.05). The time to start TEN was a predictor of infected necrosis/fluid collection (odds ratio, 4.09; P = 0.028).Delayed compared to early TEN is associated with higher mortality, increased frequency of infected necrosis/fluid collections, respiratory failure, and a need for intensive care unit hospitalization. Enteral nutrition in SAP should be started within 48 hours after admission to hospital.

Proton pump inhibitors (PPIs) may increase the risk of Clostridium difficile infections. There are interactions between gut microbiota and innate immune cells including neutrophils. We evaluated the effect of treatment with omeprazole on the gut microflora and neutrophil function.In 50 patients, we evaluated the effect of 4-week omeprazole treatment (n=25 with 20mg per day and n=25 with 20mg twice daily) on intragastric pH, results of stool culture and lactulose hydrogen breath test (LHBT) and neutrophil function.The treatment caused significant increase of the mean intragastric pH, especially in the group with 20mg omeprazole twice daily (from 2.05±0.59 to 5.06±1.6, P0.001). In LHBT, the increase of hydrogen concentration was observed in higher percentage of patients with 20mg of omeprazole twice daily, compared to patients with the lower dose (42.1% vs 29.4%; ns). Four weeks of omeprazole treatment have caused considerable changes in stool culture results. Patients treated with higher dose of omeprazole have had some tendency to decrease diversity of colonic microflora in comparison with patients treated with the lower dose of omeprazole. Treatment with omeprazole did not result in C. difficile positive stool culture and had no significant effect on neutrophil function.Omeprazole treatment have caused considerable changes in stool culture results. Patients treated with the higher dose had some tendency to decreased diversity of colonic microflora and towards changes in fermenting bacteria of the gut. The potential effect of omeprazole on gut microflora does not depend on neutrophil function deterioration.

OBJECTIVES The aim of this study was to assess the functional state of platelets in patients with mild acute pancreatitis and severe acute pancreatitis (S-AP). METHODS The number of platelets and their morphological parameters were measured with Advia 2120. β-Thromboglobulin and platelet factor 4 concentrations were determined by enzyme-linked immunosorbent assay method. To evaluate the expression of platelet glycoproteins, flow cytometry method was used. RESULTS At the time of admission, a multiparameter evaluation of the platelets' function in AP patients showed enhanced platelet activation, which was reflected by an increase in the number of large platelets, concentration of degranulation markers (platelet factor 4 and β-thromboglobulin), expression of glycoprotein (Gp) IIb/IIIa, and decreased mean platelet component. Only in S-AP patients at day 1 a decreased number of platelets and high expression of P-selectin and GpIa were observed, which may suggest their prognostic value. At day 30, the procoagulation state was still present in S-AP patients, because of increased platelets and number of large platelets as well as high GpIIb/IIIa expression. CONCLUSIONS These results may indicate an important role of platelet activation in the pathogenesis of acute pancreatitis and the development of complications in S-AP.

Purpose Determination of the type and frequency of complications developing after diagnostic and therapeutic endoscopic retrograde cholangiopancreatography (ERCP) as well as the risk factors predisposing to them. Material/Methods The retrospective study, including 734 ERCP performed in 550 patients, with 404 (55%) ES (endoscopic sphincterotomy) during a 4-year period. Results Among 734 ERCP procedures, 76.4% (561) had both diagnostic and therapeutic purpose, 15.2% (112) were only diagnostic. Complications developed after 26 procedures (3.5%): acute pancreatitis (AP) in 8 patients (1.09%), cholangitis in 7 (0.95%) and delayed bleeding in 11 (1.5%) patients. After 49 (6.7%) ES immediate bleeding was observed. The risk factors for AP were: unintentional pancreatic duct contrasting, mechanical lithotripsy, the use of the “pre-cut” technique and bile duct dilatation. Cholangitis was more common in cases with difficult cannulation at older age and with lower baseline bilirubin level. The risk factors for delayed bleeding were: location of the ampulla of Vater in the diverticulum and the use of the “pre-cut” technique. Immediate bleeding was more frequent after revision of bile ducts with Dormia's basket or with balloon, after introduction of contrast medium to the pancreatic duct or in ductal cholelithiasis. Conclusions ERCP performed in the endoscopy unit of a specialist hospital department is a relatively safe procedure, with a low burden of complications as compared to the benefits it provides to appropriately qualified patients.

Background Specialized intestinal metaplasia (SIM) in Barrett’s esophagus is a risk factor of esophageal adenocarcinoma. It often occurs focally and cannot be distinguished from surrounding columnar epithelium with conventional endoscopy. Aims The purpose of this study was evaluation of methylene blue (MB) staining and magnification endoscopy with comparison of pit-pattern classifications according to Endo and Guelrud, in detection of SIM in Barrett’s esophagus. Methods Twenty-five patients, aged 33–77 years (average 57 years), with displacement of Z line were prospectively enrolled and underwent gastroscopy with the use of magnification up to 115 times (Olympus GIF Q160Z). Biopsy for histopathologic examination was taken from sites stained with MB and/or places with particular pit patterns. A control group consisted of ten patients with normal gastro-esophageal junction. Results SIM was proved in nine patients, and significantly more frequently in patients with hiatal hernia and Barrett’s segment longer than 3 cm. Round or thin linear pit patterns according to Guelrud’s and small round and straight pit patterns according to Endo’s classification were coupled with columnar epithelium. SIM was associated with deep linear and foveolar pit patterns in Guelrud’s classification. Other pit patterns were less characteristic. Both classifications had high sensitivity (Endo’s 85.7%, Guelrud’s 92.8%) but poor specificity (respectively, 21.15 and 28.4%) in detection of SIM. Sensitivity and specificity of MB staining were, respectively, 71.4 and 40.6%. Conclusions Despite existing association between mucosal surface structure and histology, we find no convincing data indicating that pit-pattern evaluation may replace multiple biopsies taken according to recommendations from Seattle for detection of SIM in Barrett’s esophagus.

We report the case of a 69-year-old man with a spontaneous gastrobiliary fistula. Internal biliary fistulas are usually the result of longstanding, untreated choledocholithiasis, cholecystolithiasis, peptic ulcers or rarely neoplasia. This patient’s unspecific clinical picture led to a late diagnosis, which was made during surgery. How to cite this article: Chwiesko A, Jurkowska G, Kedra B, Okulczyk B, Kamocki Z, Dabrowski A. A Rare Spontaneous Gastrobiliary Fistula. Euroasian J Hepato-Gastroenterol 2014;4(2):101-103.

Acoustocerebrography is a novel, non-invasive, transcranial ultrasonic diagnostic method based on the transmission of multispectral ultrasound signals propagating through the brain tissue. Dedicated signal processing enables the estimation of absorption coefficient, frequency-dependent attenuation, speed of sound and tissue elasticity. Hypertension and atrial fibrillation are well known factors correlated with white matter lesions, intracerebral hemorrhage and cryptogenic stroke numbers. The aim of this study was to compare the acoustocerebrography signal in the brains of asymptomatic atrial fibrillation patients with and without hypertension. The study included 97 asymptomatic patients (40 female and 57 male, age 66.26 ± 6.54 years) who were clinically monitored for atrial fibrillation. The patients were divided into two groups: group I (patients with hypertension) n = 75, and group II (patients without hypertension) n = 22. Phase and amplitude of all spectral components for the received signals from the brain path were extracted and compared to the phase and amplitude of the transmitted pulse. Next, the time of flight and the attenuation of each frequency component were calculated. Additionally, a fast Fourier transformation was performed and its features were extracted. After introducing a machine learning technique, the ROC plot of differentiations between group I and group II with an AUC of 0.958 (sensitivity 0.99 and specificity 0.968) was obtained. It can be assumed that the significant difference in the acoustocerebrography signals in patients with hypertension is due to changes in the brain tissue, and it allows for the differentiating of high-risk patients with asymptomatic atrial fibrillation and hypertension.

Ghrelin and leptin are hormones regulating appetite and metabolic processes. Adiponectin plays an important role in the modulation of glucose and lipid metabolism.The objective of the study was to evaluate the levels of plasma ghrelin, leptin, and adiponectin in obese subjects treated with bioenterics intragastric balloon (BIB), low-calorie diet (1500 kcal), and physical exercise.BIB was placed for 6 months in 21 subjects with body mass index 47.3 +/- 5.7. The control group consisted of 15 morbidly obese subjects treated with a low-calorie diet and physical effort. Plasma hormone levels were determined by RIA.In the BIB group, the insertion of the balloon caused a considerable reduction in body mass over a 6-month period (17.1 +/- 8.0 kg) as compared with the control group (3.2 +/- 6.4 kg). After 1 month, the levels of ghrelin increased from 621.9 +/- 182.4 to 903.9 +/- 237 pg/ml and thereafter gradually decreased, reaching the starting level 3 months after the removal of the balloon. In the same group, the levels of leptin decreased from 61.3 +/- 36.7 to 39.9 +/- 17.5 ng/ml. In the control group, the corresponding levels of ghrelin and leptin remained relatively stable. During the observation period, in the BIB group, the levels of adiponectin remained unchanged as opposed to a transient increase noted in the control group.In patients with morbid obesity, weight loss induced by BIB is associated with a decrease in plasma leptin and a transient elevation of plasma ghrelin. It is likely that the changes in hormones regulating the energy balance caused by BIB can prevent an increase in adiponectin level.

Background: The diagnostic value of ambulatory ECG monitoring in screening for coronary artery disease has been studied in diverse and usually small groups of patients. There are no studies evaluating the diagnostic value of Holter recorded ST depression using the Bayes' theorem of probability, which accounts for the prevalence of the disease in prespecified populations. Purpose: Applying the Bayes' theorem, this study aimed to examine the diagnostic value of Holterrecorded 1-mm ST depression in patients screened for coronary artery disease (CAD) and to identify groups of patients who may benefit from diagnostic ST segment monitoring in ambulatory ECG recordings. Methods: The ST segment analysis was performed in 24-hour ambulatory ECG monitoring of 460 subjects (375 males; aged 35–65, mean 48.6 years), who were screened for CAD and had coronary angiography. The Bayes' formulae were used to calculate the predictive value of ST segment monitoring (posttest likelihood of CAD) in comparison to pretest likelihood of the disease based on age, gender, and symptoms. Results: The 1-mm ST depression was identified in the ambulatory ECG monitoring in 203 (44%) patients. CAD was angiographically confirmed in 279 (61%) patients. The 1-mm ST depression had 54% sensitivity, 71% specificity, 74% positive predictive value, and 50% negative predictive value for CAD. The Bayes' theorem analysis with adjustment for pretest likelihood of the disease in relation to age, gender, and symptoms showed that 1-mm ST segment depression is significant diagnostically in patients with pretest likelihood of the disease exceeding 75%, i.e., in males aged 35–45 years and females aged 56–65 years, both with typical angina. In other groups of patients regardless of the symptoms, age, and gender, detection of ST segment depression does not improve the diagnostic process. A negative result (absence of ST segment depression) can be helpful, confirming the absence of CAD in patients with 15%–25% pretest likelihood of the disease, i.e., in females aged 35–45 years with atypical angina pains and in males aged 46–55 years with nonanginal chest pains. Conclusions: Based on our observations, the 1-mm ST segment depression detected on 24-hour ambulatory ECG monitoring indicates a high likelihood of CAD in patients with < 75% pretest likelihood of the disease. ST segment analysis in other age and gender relative groups of patients, regardless of the nature of their symptoms, does not significantly improve diagnosis process.

Background Elevated serum concentrations of macrophage-colony stimulating factor (M-CSF) have been found in a variety of malignant diseases. The aim of our study was to assess correlations between serum levels of M-CSF and clinicopathological features and survival rates in patients with colorectal cancer (CRC). Patients/methods M-CSF and the established tumor markers (carcinoembryonic antigen — CEA and carbohydrate antigen — CA 19-9) were investigated in the sera of 116 colorectal cancer patients and correlated with the clinical parameters of the disease and with the survival of patients. We compared M-CSF serum levels in CRC with colorectal adenoma patients. M-CSF was determined using enzyme-linked immunosorbent assay (ELISA). Tumor markers were measured by microparticle enzyme immunoassays (MEIA). Results CRC patients had significantly higher M-CSF and tumor markers levels compared to healthy controls and colorectal adenoma patients, with a significant association between M-CSF levels, disease stage and lymph node metastasis. Serum levels of M-CSF and CEA decreased significantly after radical resection of the tumor. Moreover, the multivariate analysis showed that the serum level of M-CSF in CRC patients was an independent prognostic factor. Conclusion These findings suggest the potential clinical use of circulating M-CSF measurements, particularly in estimating prognosis for patients with CRC.

The purpose of this study was to evaluate the usefulness of serum total sialic acid (SA) for discrimination of malignant and nonmalignant jaundice. Serum SA concentration and its ratio with total protein (SA/TP) were determined in 55 patients with jaundice: 25 malignant and 30 nonmalignant. SA was estimated by enzymatic method. Serum total SA and the ratio SA/TP were significantly higher in malignant than in nonmalignant jaundice. Diagnostic sensitivity of SA and the ratio of SA/TP in both types of jaundice reached the value of 95.8%. The specificity, positive and negative predictive values, and efficiency of SA and SA/TP were higher in malignant than in nonmalignant jaundice. Areas under ROC curves for SA and the ratio of SA/TP in malignant jaundice were higher than in nonmalignant, but there were not statistically significant differences. SA levels and the ratio of SA/TP do not have the ability to discriminate between these types of jaundice.

Background: The balanced activity of matrix metalloproteinases and their tissue inhibitors is an important, albeit still not completely understood, determinant of extracellular matrix homeostasis, a factor involved in the pathogenesis of acute pancreatitis (AP). Aims: The aim of this study was to compare serum concentrations of matrix metalloproteinase 9 (MMP-9) and its tissue inhibitor (TIMP-1) in patients with AP of various severity and to investigate their relationship with prognostic indicators of AP severity, e. g., polymorphonuclear leukocyte elastase (PMN-E). Patients and Methods: The study included 37 patients with mild (n = 18) or severe AP (n = 19) and 15 healthy controls. Serum concentrations of MMP-9 and TIMP-1 were determined on admission (day 1) and on days 2, 3, 5 and 10. Results: Throughout the study period, the serum MMP-9 concentration in patients with severe AP was significantly higher than those in individuals with mild AP and in healthy controls. In turn, the serum MMP-9 concentrations in persons with mild AP did not differ significantly from those of the controls. The serum TIMP-1 concentrations in both groups were significantly higher than in the controls. Beginning from the 2nd day of hospital stay, the serum TIMP-1 concentration in patients with severe AP was significantly higher than in individuals with mild AP. There were significant correlations between: MMP-9 and PMN-E, TIMP-1 and PMN-E, and MMP-9 and TIMP-1. Conclusion: A disturbed balance between MMP-9 and TIMP-1 observed during the early stages of severe AP suggests that endogenous TIMP-1 is unable to prevent excessive activation and release of MMP-9. MMP-9 may represent a new marker of AP severity.

Gastro-esophageal reflux disease (GERD) may cause chest pain. The aim was to determine the correlation between ischemia and gastro-esophageal reflux in patients with CAD and to assess the influence of short-term "anti-reflux" therapy on the ischemia in patients with GERD and CAD.Fifty patients with angiographically proven CAD underwent simultaneous 24-h continuous ECG and esophageal pH monitoring. We assessed the number of ST-segment depression episodes (ST dep.) and total duration of ischemic episodes, expressed as total ischemic burden (TIB). In pH-metry, we assessed: time percentage of pH lower than 4, total time of pH lower than 4 and the number of pathological refluxes (PR). Patients fulfilling the GERD criteria received a 7-day therapy with omeprazole 20 mg bid. On the 7th day of therapy, simultaneous Holter and esophageal pH monitoring was repeated.Total number of 224 PRs in 42 patients (84%) was recorded during esophageal pH-metry. GERD criteria were fulfilled in 23 patients (46%). Out of 218 episodes of ST dep., 45 (20.6%) correlated with PR. GERD patients had larger TIB and higher number of ST dep. (p0.015 and p0.035, respectively). The anti-reflux therapy reduced all analyzed parameters of esophageal pH monitoring (p0.0022) as well as the number of ST dep. (p0.012) and TIB (p0.05).Gastro-esophageal reflux disease is common in patients with CAD and may provoke myocardial ischemia. Short-term proton pump inhibitors therapy that restores normal esophageal pH significantly reduces myocardial ischemia, possibly due to elimination of acid-derived esophago-cardiac reflex compromising coronary perfusion-the phenomenon known as "linked angina".

Introduction Excessive inflammatory response is one of the major causes of early mortality in acute pancreatitis (AP). Aim To evaluate the serum profiles of E-selectin, interleukin (IL)-6, and IL-10 along with their correlation to the markers of oxidative stress and neutrophil activation in patients with AP and patients with nonpancreatic acute abdominal pain (NPAAP). Methodology This prospective clinical study included 56 patients with AP (28 with mild AP and 28 with severe AP) as well as 15 patients with NPAAP. Results Serum concentrations of E-selectin, IL-10, and IL-6 and plasma concentrations of polymorphonuclear leukocyte elastase (determined on days 1-3, 5, and 10 after admission) were the highest in severe AP during the first 3 days and then declined. At day 10, the E-selectin level in severe AP was still higher than that in mild AP, and the IL-10 concentration increased again. There was no elevation in the E-selectin concentration in NPAAP patients, and IL-10 levels remained unchanged in mild AP. Oxidative stress, measured by serum malondialdehyde and 4-hydroxyalkenals levels, was the most pronounced in severe AP. Conclusions The serum E-selectin concentration is markedly elevated in severe AP and is less in mild AP but not in NPAAP. It may result from stimulation with different inflammatory mediators or indicate vascular endothelium injury mediated by oxidative stress, especially in the severe form of AP.

In a group of 193 postinfarction patients with ventricular premature beats on a resting 12-lead ECG, the dispersion of QT and JT intervals was calculated as a difference between maximum and minimum QT and JT intervals in ventricular premature beats. During a follow-up of 38 ± 17 months, death from all causes was noted in 56 patients. Univariate predictors of mortality included QT dispersion ≥100 ms, JT dispersion ≥100 ms, left ventricular ejection fraction 60 years. At multivariate Cox proportional hazards survival analysis, only QT dispersion ≥100 ms, left ventricular ejection fraction 2 = 23.60, p = 0.0000).

This paper presents results of a simulation study of complex dynamic phenomena in arrays composed of interacting chaotic circuits. Such arrays can be thought of as a new paradigm for modelling non-linear phenomena in spatially extended (high-dimensional or infinite-dimensional) systems and active media with potential applications in signal processing. Depending on the connection structure between the cells, the array can show disorganized hyperchaotic behaviour or spatially ordered chaotic waves. Patterns of behaviour depending on the excitation of the array and the connection structure are studied in this paper. Chua circuits are taken as standard chaotic cells.

Background: Clinical and experimental observations indicate that reduced beat-to-beat changes in the cycle length of nonsustained ventricular tachycardia (NSVT) may portend malignant ventricular tachyarrhythmias and sudden cardiac death. The purpose of the study was to test the hypothesis that measures of ventricular rate variability during NSVT (VRV-NSVT) may be useful in identifying patients at high risk of life-threatening arrhythmic events. Methods: The study group consisted of 326 patients who had NSVT on 24-hour ECG recordings. Temporal changes in up to 10 beat-to-beat intervals of NSVT runs (V-V) were assessed. The following parameters of VRV-NSVT were calculated: (1) average value of successive differences in V-V intervals (ADVV); and (2) normalized average value of successive differences in V-V intervals (nADVV). Results: During a mean follow-up of 4 years, 52 (16%) patients had a documented episode of sustained VT or ventricular fibrillation. Patients with these arrhythmic events had significantly (P < 0.001) lower values of ADVV and nADVV variables in comparison to patients without arrhythmic events. The relative risk of malignant arrhythmic events for patients with ADW < 40 ms was 4.9 (P < 0.001), for patients with nADVV < 6%, the risk was 3.9 (P < 0.001). Conclusions: The results of this study indicate a strong and significant relationship between NSVT and the risk of subsequent malignant ventricular tachycardia. The assessment of VRV-NSVT may be useful for identifying patients at high and low risk for subsequent arrhythmic events.

Considering the important role of neutrophils' activation in the pathogenesis of acute pancreatitis (AP), the aim of our study was to evaluate the expression of leukocytes' adhesion molecules in patients with AP.Thirty-five patients (16 women and 19 men; age 32-77 years, median 56 years) with AP were prospectively included into our study. The absolute number of leukocytes was estimated by haematologic analyser. Surface neutrophils antigens (CD) were assayed by the direct fluorescence method for whole blood, using a flow cytometer.At the day 1, significant increase of ICAM-1 expression was found in patients with severe AP (S-AP) (7280 mm(-3) vs 2850 mm(-3) in healthy control; p0.05). In the days 2, 3 and 5 it sharply decreased and peaked again to 4860 mm(-3) at the day 10. In patients with mild AP (M-AP), not significant elevation of ICAM-1 quickly returned to normal level. In both forms of AP, neutrophil CD62L (L-selectin) expression reached the highest level at the day 1 (8800 mm(-3) and 9020 mm(-3), respectively in M-AP and S-AP, in comparison to 3400 mm(-3) in control; p0.05). Expression of CD69 (neutrophils' marker of early activation) significantly increased in both M-AP and S-AP.We have found an early and significant increase of peripheral blood neutrophil CD54/ICAM-1 expression, specific for S-AP but not for M-AP. It may provide a good marker predicting severe course of pancreatitis.

Acute hemorrhagic pancreatitis was induced in Wistar rats using a retrograde intraductal injection of 5% Na-taurocholate. Rats were treated with platelet-activating factor receptor (PAF) antagonist—BN 52021 (5 mg/kg) and sacrificed at 1 and 3 h after induction of acute pancreatitis. Malondialdehyde and sulfhydryl groups concentration were measured in pancreatic, lung, and liver tissue as a parameters of oxidant-antioxidant balance. We have shown that BN 52021 exerts only partial protecting effect against Na-TC-induced AP in rats. The positive effects of BN 52021 were expressed by: (1) Significant reduction of hyperamylasemia accompanied by lower malondialdehyde accumulation in pancreatic tissue; (2) Prevention of sulfl hydryl groups depletion in lung tissue; (3) Diminution of necrotic and inflammatory changes in pancreatic tissue; and (4) Improvement of survival rate. We suggest that these effects may depend on the inhibition of PAF-mediated activation and oxidant generation by phagocytes.

WNUK-WOJNAR, A.M., ET AL.: Predictors of Ventricular Tachycardia Inducibility in Programmed Electrical Stimulation and Effectiveness of Serial Drug Testing: Polish Multicenter Study. In 100 patients with IHD and complex ventricular arrhythmias, programmed electrical stimulation was performed using up to three extrastimuli at sinus rhythm, and paced 100, 120, and 140 beats/min delivered from the RV apex, outflow tract or the LV with ventricular mapping to evaluate late potentials (LP) in 41 patients. Sustained monomorphic VT (SMVT) was provoked in 91% of 42 patients with a history of VT/VF, p < 0.001, all five patients had SMVT in 24-hour ECG, p < 0.005, and 91% of 21 patients with LV dyskinesis, p < 0.01. After depolarizations were found in 62% of 21 patients with a history of VT, in 58% of 31 patients with inducible VT, p < 0.01 and in five of six patients with LV dyskinesis. In patients with inducible VT, LP had a higher amplitude (105 ± 35 vs 60 ± 47 µV) and were more delayed (202 ± 96 vs 133 ± 75 msec) than in noninducible patients. In 17 patients, serial drug testing was performed after oral administration using mexilitene, disopyramide, chinidine, propafenone, sotalol, and amiodarone. If one drug was tested, the therapy efficacy was 25% if two drugs-60%, and if three drugs-75%. In eight patients, VT was inducible in all tests, but in only one of these patients chronic antiarrhythmic therapy was not effective. We conclude that the most important predictors of VT inducibility are a history of VT or 24-hour ECG, and LV dyskinesis. Serial drug testing is efficient only when many drugs are tested, but even if VT is inducible, it does not exclude the possibility of a good clinical outcome in chronic therapy.

Alteration of the immune system is one of the major mechanisms responsible for complications in severe acute pancreatitis (AP). The aim of our study was to provide a complex evaluation of peripheral blood monocyte subsets, natural killer cells (NK cells) and cytotoxic T lymphocytes in patients with different severity forms of AP.20 patients with mild AP and 15 with severe AP (S-AP) were included in our study. Peripheral blood mononuclear cells were studied on days 1-3, 5, 10 and 30, by means of flow cytometry.In peripheral blood of patients with pancreatitis, we found a marked increase in total monocyte count. In S-AP, circulating monocytes were significantly activated, which was presumed from increased expression of HLA-DR, CD54, CD69 and CD25. Concurrent increased expression of CD95 (FasR) may indicate enhanced susceptibility of these cells to apoptosis. In patients with S-AP, a dramatic depletion of circulating NK cells (CD16/56 and CD3- CD8+) was found along with a reduction of circulating CD3+ CD8+ lymphocytes (cytotoxic T lymphocytes).Our findings suggest profound disturbances of innate cellular immunity in patients with S-AP.

AIM: To evaluate peripheral blood lymphocyte subsets in patients with acute pancreatitis (AP). METHODS: Twenty patients with mild AP (M-AP) and 15 with severe AP (S-AP) were included in our study. Peripheral blood lymphocytes were examined at d 1-3, 5, 10 and 30 by means of flow cytometry. RESULTS: A significant depletion of circulating lymphocytes was found in AP. In the early AP, the magnitude of depletion was similar for T- and B- lymphocytes. In the late course of S-AP, B-lymphocytes were much more depleted than T-lymphocytes. At d 10, strong shift in the CD7+/CD19+ ratio implicating predominance of T- over B-lymphocytes in S-AP was found. Among T-lymphocytes, the significant depletion of the CD4+ population was observed in M-AP and S-AP, while CD8+ cells were in the normal range. Lymphocytes were found to strongly express activation markers: CD69, CD25, CD28, CD38 and CD122. Serum interleukin-2 (IL-2), IL-4, IL-5, IL-10, interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α) levels were significantly increased in both forms of AP. The magnitude of elevation of cytokines known to be produced by Th2 was much higher than cytokines produced by Th1 cells. CONCLUSION: AP in humans is characterized by significant reduction of peripheral blood T- and B-lymphocytes.

Gastrointestinal perforations, leaks and fistulas may be serious and life-threatening. The increasing number of endoscopic procedures with a high risk of perforation and the increasing incidence of leakage associated with bariatric operations call for a minimally invasive treatment for these complications. The therapeutic approach can vary greatly depending on the size, location, and timing of gastrointestinal wall defect recognition. Some asymptomatic patients can be treated conservatively, while patients with septic symptoms or cardio-pulmonary insufficiency may require intensive care and urgent surgical treatment. However, most gastrointestinal wall defects can be satisfactorily treated by endoscopy. Although the initial endoscopic closure rates of chronic fistulas is very high, the long-term results of these treatments remain a clinical problem. The efficacy of endoscopic therapy depends on several factors and the best mode of treatment will depend on a precise localization of the site, the extent of the leak and the endoscopic appearance of the lesion. Many endoscopic tools for effective closure of gastrointestinal wall defects are currently available. In this review, we summarized the basic principles of the management of acute iatrogenic perforations, as well as of postoperative leaks and chronic fistulas of the gastrointestinal tract. We also described the effectiveness of various endoscopic methods based on current research and our experience.

The patterns with visible spatial regularity emerging from cooperation of a large number of chaotic dynamic elements are referred to as self-organization. In this paper we propose to use cellular neural network (CNN) with chaotic neurons having spatial irregularities as possible models of dynamics of biological functions. Two kinds of inhomogeneous structures are analysed: defects introduced by cutting off connections in some cells in one row with the neighboring rows; and spatial defects obtained by removing the cells positioned in some small area within the network. We confirm that such irregularities in some cases can cause target waves to lose their circular regularity and give rise to spiral waves-similar to those observed in abnormal operation of cardiac tissue. Another type of phenomena observed is the robustness of the spatial memory effect on the removal of cells in the network which could serve as model of some types of biological tissues where functionality is maintained despite of the fact that some of the cells die or are removed from the tissue.

In image registration it is vital to perform matching of those points in a pair of images which actually match each other, and to postpone those which do not match. It is not always known in advance, however, which points have their counterparts, and where are they located. To overcome this, we propose to use the Hausdorff distance function modified by using a voting scheme as a fitting quality function. This known function performs very well in guiding the matching process and supports stable matches even for low quality data. It also makes it possible to speed up the algorithms in various ways. An application to accuracy assessment of oncological radiotherapy is presented. Low contrast of images used to perform this task makes this application a challenging test.

To date, no information is available comparing the prognostic significance of the QT interval corrected by Bazett’s equation with that corrected by linear formulas in patients after myocardial infarction. Because several reports1,2 demonstrated that heart rate measured on a standard electrocardiogram is a strong predictor of adverse outcome in patients after myocardial infarction, it is very probable that linear adjustment of the QT interval decreases the prognostic power of corrected QT interval. The present study compares the value of linearly and nonlinearly corrected QT intervals for identifying high-risk patients, and tests the hypothesis that more accurate adjustment of the QT interval for heart rate paradoxically decreases the prognostic significance of the corrected QT interval in patients with remote myocardial infarc