BACKGROUND Although the usefulness of endoscopic scores,such as the Mayo Endoscopic Subscore(MES),Ulcerative Colitis Endoscopic Index of Severity(UCEIS),and Ulcerative Colitis Colonoscopic Index of Severity(UCCIS),and...BACKGROUND Although the usefulness of endoscopic scores,such as the Mayo Endoscopic Subscore(MES),Ulcerative Colitis Endoscopic Index of Severity(UCEIS),and Ulcerative Colitis Colonoscopic Index of Severity(UCCIS),and biomarkers such as fecal calprotectin(FC)for predicting relapse in ulcerative colitis(UC)has been reported,few studies have included endoscopic scores for evaluating the entire colon.AIM To compare the usefulness of FC value and MES,UCEIS,and UCCIS for predicting relapse in patients with UC in clinical remission.METHODS In total,75 patients with UC in clinical and endoscopic remission who visited our institution between February 2019 and March 2022 were enrolled.The diagnosis of UC was confirmed based on the clinical presentation,endoscopic findings,and histology,according to the current established criteria for UC.Fecal samples were collected the day before or after the colonoscopy for measurement of FC.Endoscopic evaluations were performed using MES,UCEIS,and UCCIS.The primary outcome measure of this study was the assessment of the association between relapse within 12 mo and MES,UCEIS,UCCIS,and FC.The secondary outcome was the comparison between endoscopic scores and biomarkers in en-rolled patients with UC with mucosal healing.RESULTSFC and UCCIS showed a significant correlation with UCEIS (r = 0.537, P < 0.001 and r = 0.957, P < 0.001, respectively).Receiver-operating characteristic analysis for predicting MES 0 showed that the area under the curve ofUCCIS was significantly higher than that of FC (P < 0.01). During the 1-year observation period, 18 (24%) patientsexperienced a relapse, and both the FC and UCCIS of the relapse group were significantly higher than that of theremission group. The cut-off values for predicting relapse were set at FC = 323 mg/kg and UCCIS = 10.2. The areaunder the curve of the receiver-operating characteristic analysis for predicting relapse did not show a significantdifference between FC and UCCIS. The accuracy of the endoscopic scores and biomarkers in predicting relapse was86.7% for UCCIS, 85.3% for UCEIS, 76.0% for FC, and 73.3% for MES.CONCLUSIONThe three endoscopic scores and FC may predict UC relapse during clinical remission. Among these scores, UCEISmay be the most useful in terms of ease of evaluation and accuracy.展开更多
BACKGROUND Periodontitis has been associated with various liver diseases.However,the relevance of periodontitis in the progression of decompensated cirrhosis remains inconclusive.In particular,it is unclear whether th...BACKGROUND Periodontitis has been associated with various liver diseases.However,the relevance of periodontitis in the progression of decompensated cirrhosis remains inconclusive.In particular,it is unclear whether the common periodontitis pathogens,Porphyromonas gingivalis(P.gingivalis)and Actinobacillus actinomycetemcomitans(A.actinomycetemcomitans),can be detected not only in the oral mucosa but also in ascites and stool.AIM To investigate the significance of periodontitis,P.gingivalis,and A.actinomycetemcomitans in cirrhosis patients with ascitic decompensation.METHODS This prospective study was conducted at the University Hospital Hamburg Eppendorf,a tertiary center in Northern Germany.A cohort of 27 patients with ascitic decompensated liver cirrhosis underwent dental examinations to assess the association between periodontitis and various clinical parameters of cirrhosis,as well as patient outcomes.PCR was used to test gingival samples,ascites,and stool for the presence of P.gingivalis and A.actinomycetemcomitans.Gingival samples were collected by probing the deepest gum pocket of a sextant and wiping them on a cotton swab.RESULTS Periodontitis was diagnosed in 22 out of 27(82%)ascite patients,which is significantly more common than in a control cohort of 100 unselected patients(59%,P=0.04).P.gingivalis was detected in the gingiva of six patients,and one of them also had P.gingivalis in their stool.However,P.gingivalis was not found in the ascites of any patient.Five out of six patients with P.gingivalis had periodontitis(83%).A.actinomycetemcomitans was not detected in any sample.Patients without periodontitis had a significantly higher mortality rate compared to those with periodontitis,and survival(Kaplan-Meier analysis)was longer in patients with periodontitis(P=0.02).Transplantfree survival was also more common in patients with periodontitis compared to those without(63%vs 0%,P=0.02).CONCLUSION Decompensated cirrhotic patients frequently suffer from periodontitis.However,there was no evidence of the translocation of P.gingivalis or A.actinomycetemcomitans into ascites.The survival of cirrhotic patients with periodontitis was not reduced.展开更多
The cure rates of Helicobacter pylori(H.pylori)eradication therapy using a proton pump inhibitor(PPI)and antimicrobial agents such as amoxicillin,clarithromycin,and metronidazole are mainly influenced by bacterial sus...The cure rates of Helicobacter pylori(H.pylori)eradication therapy using a proton pump inhibitor(PPI)and antimicrobial agents such as amoxicillin,clarithromycin,and metronidazole are mainly influenced by bacterial susceptibility to antimicrobial agents and the magnitude of the inhibition of acid secretion.Annual cure rates have gradually decreased because of the increased prevalence of H.pylori strains resistant to antimicrobial agents,especially to clarithromycin.Alternative regimens have therefore been developed incorporating different antimicrobial agents.Further,standard PPI therapy(twice-daily dosing)often fails to induce a long-term increase in intragastric pH>4.0.Increasing the eradication rate requires more frequent and higher doses of PPIs.Therapeutic efficacy related to acid secretion is influenced by genetic factors such as variants of the genes encoding drug-metabolizing enzymes(e.g.,cytochrome P450 2C19,CYP2C19),drug transporters(e.g.,multidrug resistance protein-1;ABCB1),and inflammatory cytokines(e.g.,interleukin-1β).For example,quadruple daily administration of PPI therapy potently inhibits acid secretion within 24 h,irrespective of CYP2C19 genotype.Therefore,tailored H.pylori eradication regimens that address acid secretion and employ optimal antimicrobial agents based on results of antimicrobial agent-susceptibility testing may prove effective in attaining higher eradication rates.展开更多
Irritable bowel syndrome(IBS)is a long-lasting,relapsing disorder characterized by abdominal pain/discomfort and altered bowel habits.Intestinal motility impairment and visceral hypersensitivity are the key factors am...Irritable bowel syndrome(IBS)is a long-lasting,relapsing disorder characterized by abdominal pain/discomfort and altered bowel habits.Intestinal motility impairment and visceral hypersensitivity are the key factors among its multifactorial pathogenesis,both of which require effective treatment.Voltage-gated calcium channels mediate smooth muscle contraction and endocrine secretion and play important roles in neuronal transmission.Antispasmodics are a group of drugs that have been used in the treatment of IBS for decades.Alverine citrate,a spasmolytic,decreases the sensitivity of smooth muscle contractile proteins to calcium,and it is a selective 5-HT1A receptor antagonist.Alverine,in combination with simethicone,has been demonstrated to effectively reduce abdominal pain and discomfort in a large placebo-controlled trial.Mebeverine is a musculotropic agent that potently blocks intestinal peristalsis.Non-placebo-controlled trials have shown positive effects of mebeverine in IBS regarding symptom control;nevertheless,in recent placebo-controlled studies,mebeverine did not exhibit superiority over placebo.Otilonium bromide is poorly absorbed from the GI tract,where it acts locally as an L-type calcium channel blocker,an antimuscarinic and a tachykinin NK2receptor antagonist.Otilonium has effectively reduced pain and improved defecation alterations in placebocontrolled trials in IBS patients.Pinaverium bromide is also an L-type calcium channel blocker that acts locally in the GI tract.Pinaverium improves motility disorders and consequently reduces stool problems in IBS patients.Phloroglucinol and trimethylphloroglucinol are non-specific antispasmodics that reduced pain in IBS patients in a placebo-controlled trial.Antispasmodics have excellent safety profiles.T-type calcium channel blockers can abolish visceral hypersensitivity in animal models,which makes them potential candidates for the development of novel therapeutic agents in the treatment of IBS.展开更多
AIM: To assess the effect of our novel cell-permeable nuclear factor-kappaB (NF-κB) inhibitor peptide PN50 in an experimental model of acute pancreatitis. PN50 was produced by conjugating the cell-penetrating penetra...AIM: To assess the effect of our novel cell-permeable nuclear factor-kappaB (NF-κB) inhibitor peptide PN50 in an experimental model of acute pancreatitis. PN50 was produced by conjugating the cell-penetrating penetratin peptide with the nuclear localization signal of the NF-κB p50 subunit.METHODS: Pancreatitis was induced in male Wistar rats by administering 2×100 μg/kg body weight of cholecystokininoctapeptide (CCK) intraperitoneally (IP) at an interval of 1 h. PN50-treated animals received 1 mg/kg of PN50 IP 30 min before or after the CCK injections. The animals were sacrificed 4 h after the first injection of CCK.RESULTS: All the examined laboratory (the pancreatic weight/body weight ratio, serum amylase activity,pancreatic levels of TNF-α and IL-6, degree of lipid peroxidation, reduced glutathione levels, NF-κB binding activity, pancreatic and lung myeloperoxidase activity) and morphological parameters of the disease were improved before and after treatment with the PN50 peptide.According to the histological findings, PN50 protected the animals against acute pancreatitis by favoring the induction of apoptotic, as opposed to necrotic acinar cell death associated with severe acute pancreatitis.CONCLUSION: Our study implies that reversible inhibitors of stress-responsive transcription factors like NF-κB might be clinically useful for the suppression of the severity of acute pancreatitis.展开更多
AIM: The sphincter of Oddi (SO) plays an important role in delivery of bile into the duodenum. To establish whether vasoactive intestinal polypeptide (VIP) and nitric oxide (NO) were involved in phasic contractile act...AIM: The sphincter of Oddi (SO) plays an important role in delivery of bile into the duodenum. To establish whether vasoactive intestinal polypeptide (VIP) and nitric oxide (NO) were involved in phasic contractile activity of the rabbit SO stimulated by cholecystokinin-octapeptide (CCK-8).METHODS: Isolated SO muscle rings were cleaned of fat and mounted horizontally on two small L-shaped hooksone of which was connected to a force transducer for the measurement of isometric tension. The experiments were carried out in a thermostatically controlled (37±0.2℃)organ bath (5 mL) containing Krebs solution. The organ fluid was gassed with 95% O2 and 50 mL/L CO2 to keep the pH at 7.40±0.05. Contractile responses to CCK-8 (1μmol/L) were evaluated in the presence and absence of N^G-nitro-L-arginine (LNNA), an inhibitor of NO synthase (100μmol/L), and (p-chloro-D-Phe^6-Leu^17)-VIP (VIPa,30μmol/L), a VIP receptor antagonist.RESULTS: CCK-8 stimulated the phasic activity of the SO.NO synthase inhibition increased the frequency and amplitude of contractions with a slight increase in developed tension.Pre-incubation with VIPa also attenuated this CCK-8 effect.The combined application of LNNA and VIPa abolished the phasic activity of the muscle rings with a marked increase in tension in response to CCK-8.CONCLUSION: VIP and NO together contribute to an increase in phasic activity of SO.展开更多
AIM:To investigate whether potent acid inhibition is effective in non-erosive reflux disease (NERD) refractory to standard rabeprazole (RPZ) treatment. METHODS:We treated 10 Japanese patients with NERD resistant to st...AIM:To investigate whether potent acid inhibition is effective in non-erosive reflux disease (NERD) refractory to standard rabeprazole (RPZ) treatment. METHODS:We treated 10 Japanese patients with NERD resistant to standard dosages of RPZ:10 mg or 20 mg od,20 mg bid,or 10 mg qid for 14 d. All patients completed a frequency scale for symptoms of gastroesophageal reflux disease questionnaire frequency scale for the symptoms of GERD (FSSG); and underwent 24 h pH monitoring on day 14. RESULTS:With increased dosages and frequency of administration of RPZ,median intragastric pH significantly increased,and FSSG scores significantly decreased. With RPZ 10 mg qid,potent acid inhibition was attained throughout 24 h. However,five subjects were refractory to RPZ 10 mg qid,although the median intragastric pH in these subjects (6.6,range:6.2-7.1) was similar to that in the remaining five responsive subjects (6.5,range:5.3-7.3). With baseline RPZ 10 mg od,FSSG scores in responsive patients improved by > 30%,whereas there was no significant decrease in the resistant group. CONCLUSION:NERD patients whose FSSG score fails to decrease by > 30% after treatment with RPZ 10 mg od for 14 d are refractory to higher dosage.展开更多
AIM:To analyze the effect of chemotherapeutic drugs and specific kinase inhibitors,in combination with the death receptor ligand tumor necrosis factor-related apoptosis inducing ligand(TRAIL),on overcoming TRAIL resis...AIM:To analyze the effect of chemotherapeutic drugs and specific kinase inhibitors,in combination with the death receptor ligand tumor necrosis factor-related apoptosis inducing ligand(TRAIL),on overcoming TRAIL resistance in hepatocellular carcinoma(HCC)and to study the efficacy of agonistic TRAIL antibodies,as well as the commitment of antiapoptotic BCL-2 proteins, in TRAIL-induced apoptosis. METHODS:Surface expression of TRAIL receptors (TRAIL-R1-4)and expression levels of the antiapoptotic BCL-2 proteins MCL-1 and BCL-xL were analyzed by flow cytometry and Western blotting,respectively. Knock-down of MCL-1 and BCL-xL was performed by transfecting specific small interfering RNAs.HCC cellswere treated with kinase inhibitors and chemotherapeutic drugs.Apoptosis induction and cell viability were analyzed via flow cytometry and 3-(4,5-Dimethyl-thiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. RESULTS:TRAIL-R1 and-R2 were profoundly expressed on the HCC cell lines Huh7 and Hep-G2. However,treatment of Huh7 and Hep-G2 with TRAIL and agonistic antibodies only induced minor apoptosis rates.Apoptosis resistance towards TRAIL could be considerably reduced by adding the chemotherapeutic drugs 5-fluorouracil and doxorubicin as well as the kinase inhibitors LY294002[inhibition of phosphoinositol- 3-kinase(PI3K)],AG1478(epidermal growth factor receptor kinase),PD98059(MEK1),rapamycin(mam- malian target of rapamycin)and the multi-kinase inhibitor Sorafenib.Furthermore,the antiapoptotic BCL-2 proteins MCL-1 and BCL-xL play a major role in TRAIL resistance:knock-down by RNA interference increased TRAIL-induced apoptosis of HCC cells.Additionally, knock-down of MCL-1 and BCL-xL led to a significant sensitization of HCC cells towards inhibition of both c-Jun N-terminal kinase and PI3K.CONCLUSION:Our data identify the blockage of survival kinases,combination with chemotherapeutic drugs and targeting of antiapoptotic BCL-2 proteins as promising ways to overcome TRAIL resistance in HCC.展开更多
AIM: To investigate patient-reported outcomes from, and adherence to, a low FODMAP diet among patients suffering from irritable bowel syndrome and inflammatory bowel disease.METHODS: Consecutive patients with irritabl...AIM: To investigate patient-reported outcomes from, and adherence to, a low FODMAP diet among patients suffering from irritable bowel syndrome and inflammatory bowel disease.METHODS: Consecutive patients with irritable bowel syndrome(IBS) or inflammatory bowel disease(IBD) and co-existing IBS fulfilling the ROME Ⅲ criteria, who previously attended an outpatient clinic for low FODMAP diet(LFD) dietary management and assessment by a gastroenterologist, were invited to participate in a retrospective questionnaire analysis. The questionnaires were sent and returned by regular mail and gathered information on recall of dietarytreatment, efficacy, symptoms, adherence, satisfaction, change in disease course and stool type, and quality of life. Before study enrolment all patients had to sign an informed written consent.RESULTS: One hundred and eighty patients were included, 131(73%) IBS and 49(27%) IBD patients. Median age was 43 years(range: 18-85) and 147(82%) were females. Median follow-up time was 16 mo(range: 2-80). Eighty-six percent reported either partial(54%) or full(32%) efficacy with greatest improvement of bloating(82%) and abdominal pain(71%). The proportion of patients with full efficacy tended to be greater in the IBD group than in the IBS group(42% vs 29%, P = 0.08). There was a significant reduction in patients with a chronic continuous disease course in both the IBS group(25%, P < 0.001) and IBD group(23%, P = 0.002) along with a significant increase in patients with a mild indolent disease course of 37%(P < 0.001) and 23%(P = 0.002), respectively. The proportion of patients having normal stools increased with 41% in the IBS group(P < 0.001) and 66% in the IBD group(P < 0.001). One-third of patients adhered to the diet and high adherence was associated with longer duration of dietary course(P < 0.001). Satisfaction with dietary management was seen in 83(70%) IBS patients and 24(55%) IBD patients. Eightyfour percent of patients lived on a modified LFD, where some foods rich in FODMAPs were reintroduced, and 16% followed the LFD by the book without deviations. Wheat, dairy products, and onions were the foods most often not reintroduced by patients.CONCLUSION: These data suggest that a diet low in FODMAPs is an efficacious treatment solution in the management of functional bowel symptoms for IBS and IBD patients.展开更多
Acute pancreatitis (AP) is a serious inflammatory disease with rising incidence both in the adult and pediatric populations. It has been shown that mitochondrial injury and energy depletion are the earliest intracellu...Acute pancreatitis (AP) is a serious inflammatory disease with rising incidence both in the adult and pediatric populations. It has been shown that mitochondrial injury and energy depletion are the earliest intracellular events in the early phase of AP. Moreover, it has been revealed that restoration of intracellular ATP level restores cellular functions and defends the cells from death. We have recently shown in a systematic review and meta-analysis that early enteral feeding is beneficial in adults; however, no reviews are available concerning the effect of early enteral feeding in pediatric AP. In this minireview, our aim was to systematically analyse the literature on the treatmentof acute pediatric pancreatitis. The preferred reporting items for systematic review(PRISMA-P) were followed, and the question was drafted based on participants, intervention, comparison and outcomes: P: patients under the age of twenty-one suffering from acute pancreatitis; I: early enteral nutrition (per os and nasogastric- or nasojejunal tube started within 48 h); C: nil per os therapy; O: length of hospitalization, need for treatment at an intensive care unit, development of severe AP, lung injury (including lung oedema and pleural effusion), white blood cell count and pain score on admission. Altogether, 632 articles (Pub Med: 131; EMBASE: 501) were found. After detailed screening of eligible papers, five of them met inclusion criteria. Only retrospective clinical trials were available. Due to insufficient information from the authors, it was only possible to address length of hospitalization as an outcome of the study. Our mini-meta-analysis showed that early enteral nutrition significantly(SD = 0.806, P = 0.034) decreases length of hospitalization compared with nil per os diet in acute pediatric pancreatitis. In this minireview, we clearly show that early enteral nutrition, started within 24-48 h, is beneficial in acute pediatric pancreatitis. Prospective studies and better presentation of research are crucially needed to achieve a higher level of evidence.展开更多
BACKGROUND Epidemiologic studies have revealed a decrease in the prevalence of Helicobacter pylori(H.pylori)infection in Western Europe.AIM To obtain data regarding the prevalence of H.pylori in Csongrád and B...BACKGROUND Epidemiologic studies have revealed a decrease in the prevalence of Helicobacter pylori(H.pylori)infection in Western Europe.AIM To obtain data regarding the prevalence of H.pylori in Csongrád and Békés Counties in Hungary,evaluate the differences in its prevalence between urban and rural areas,and establish factors associated with positive seroprevalence.METHODS One-thousand and one healthy blood donors[male/female:501/500,mean age:40(19–65)years]were enrolled in this study.Subjects were tested for H.pylori IgG antibody positivity via enzyme-linked immunosorbent assay.Subgroup analysis by age,gender,smoking habits,alcohol consumption,and urban vs nonurban residence was also performed.RESULTS The overall seropositivity of H.pylori was 32%.It was higher in males(34.93%vs 29.2%,P=0.0521)and in rural areas(36.2%vs 27.94%,P=0.0051).Agricultural/industrial workers were more likely to be positive for infection than office workers(38.35%vs 30.11%,P=0.0095)and rural subjects in Békés County than those in Csongrád County(43.36%vs 33.33%,P=0.0015).CONCLUSION Although the prevalence of H.pylori infection decreased in recent decades in Southeast Hungary,it remains high in middle-aged rural populations.Generally accepted risk factors for H.pylori positivity appeared to be valid for the studied population.展开更多
AIM: To explore the propriety of providing hepatitis B virus(HBV) genotypes F and H with two distinct genotypes.METHODS: Eleven HBV isolates of genotype F (HBV/F)were recovered from patients living in San Francisco,Ja...AIM: To explore the propriety of providing hepatitis B virus(HBV) genotypes F and H with two distinct genotypes.METHODS: Eleven HBV isolates of genotype F (HBV/F)were recovered from patients living in San Francisco,Japan, Panama, and Venezuela, and their full-length sequences were determined. Phylogenetic analysis was carried out among them along with HBV isolates previously reported.RESULTS: Seven of them clustered with reported HBV/F isolates in the phylogenetic tree constructed on the entire genomic sequence. The remaining four flocked on another branch along with three HBV isolates formerly reported as genotype H. These seven HBV isolates, including the four in this study and the three reported, had a sequence divergence of 7.3-9.5% from the other HBV/F isolates,and differed by ＞ 13.7% from HBV isolates of the other six genotypes (A-E and G). Based on a marked genomic divergence, falling just short of ＞8% separating the seven genotypes, these seven HBV/F isolates were classified into F2 subtype and the former seven into F1 subtype provisionally. In a pairwise comparison of the S-gene sequences among the 7 HBV/F2 isolates and against 47HBV/F1 isolates as well as 136 representing the other six genotypes (A-E and G), two clusters separated by distinct genetic distances emerged.CONCLUSION: Based on these analyses, classifying HBV/F isolates into two subtypes (F1 and F2) would be more appropriate than providing them with two distinct genotypes (F and H).展开更多
Ultrasound is an undervalued non-invasive examination in the diagnosis of colonic diseases. It has been replaced by the considerably more expensive magnetic resonance imaging and computed tomography, despite the fact ...Ultrasound is an undervalued non-invasive examination in the diagnosis of colonic diseases. It has been replaced by the considerably more expensive magnetic resonance imaging and computed tomography, despite the fact that, as first examination, it can usefully supplement the diagnostic process. Transabdominal ultrasound can provide quick information about bowel status and help in the choice of adequate further examinations and treatment. Ultrasonography,as a screening imaging modality in asymptomatic patients can identify several colonic diseases such as diverticulosis, inflammatory bowel disease or cancer. In addition, it is widely available, cheap, non-invasive technique without the use of ionizing radiation, therefore it is safe to use in childhood or during pregnancy, and can be repeated at any time. New ultrasound techniques such as elastography, contrast enhanced and Doppler ultrasound, miniprobes rectal and transperineal ultrasonography have broadened the indication. It gives an overview of the methodology of various ultrasound examinations, presents the morphology of normal bowel wall and the typical changes in different colonic diseases. We will pay particular attention to rectal and transperineal ultrasound because of their outstanding significance in the diagnosis of rectal and perineal disorders. This article seeks to overview the diagnostic impact and correct indications of bowel ultrasound.展开更多
AIM:To investigate intestinal alkaline phosphatase(iAP) in the intestinal mucosa of children with inflammatory bowel disease(IBD).METHODS:Colonic biopsy samples were taken from 15 newly diagnosed IBD patients and from...AIM:To investigate intestinal alkaline phosphatase(iAP) in the intestinal mucosa of children with inflammatory bowel disease(IBD).METHODS:Colonic biopsy samples were taken from 15 newly diagnosed IBD patients and from 10 healthy controls.In IBD patients,specimens were obtainedboth from inflamed and non-inflamed areas.The iAP mRNA and protein expression was determined by reverse transcription-polymerase chain reaction and Western blotting analysis,respectively.Tissue localization of iAP and Toll-like receptor(TLR) 4 was investigated by immunofluorescent staining.RESULTS:The iAP protein level in the inflamed mucosa of children with Crohn's disease(CD) and ulcerative colitis(UC) was significantly decreased when compared with controls(both P < 0.05).Similarly,we found a significantly decreased level of iAP protein in the inflamed mucosa in CD compared with non-inflamed mucosa in CD(P < 0.05).In addition,the iAP protein level in inflamed colonic mucosa in patients with UC was decreased compared with non-inflamed mucosa in patients with CD(P < 0.05).iAP protein levels in the non-inflamed mucosa of patients with CD were similar to controls.iAP mRNA expression in inflamed colonic mucosa of children with CD and UC was not significantly different from that in non-inflamed colonic mucosa with CD.Expression of iAP mRNA in patients with noninflamed mucosa and in controls were similar.Co-localization of iAP with TLR4 showed intense staining with a dotted-like pattern.iAP was present in the inflamed and non-inflamed mucosa of patients with CD,UC,and in control biopsy specimens,irrespective of whether it was present in the terminal ileum or in the colon.However,the fluorescent signal of TLR4 was more pronounced in the colon compared with the terminal ileum in all groups studied.CONCLUSION:Lower than normal iAP protein levels in inflamed mucosa of IBD patients may indicate a role for iAP in inflammatory lesions in IBD.Based on our results,administration of exogenous iAP enzyme to patients with the active form of IBD may be a therapeutic option.展开更多
AIM: To evaluate the value of MR cholangiopancreatography (MRCP) in patients in whom endoscopic retrograde cholangiopancreatography (ERCP) was unsuccessfully performed by experts in a tertiary center. METHODS: From Ja...AIM: To evaluate the value of MR cholangiopancreatography (MRCP) in patients in whom endoscopic retrograde cholangiopancreatography (ERCP) was unsuccessfully performed by experts in a tertiary center. METHODS: From January 2000 to June 2003, 22 patients fulfilled the inclusion criteria. The indications for ERCP were obstructive jaundice (n = 9), abnormal liver enzymes (n=8),suspected chronic pancreatitis (n = 2), recurrent acute pancreatitis (n = 2), or suspected pancreatic cancer (n=1). The reasons for the ERCP failure were the postsurgical anatomy (n = 7), duodenal stenosis (n = 3), duodenal diverticulum (n = 2), and technical failure (n = 10). MRCP images were evaluated before and 5 and 10 min after i.v. administration of 0.5 IU/kg secretin.RESULTS: The MRCP images were diagnosed in all 21patients. Five patients gave normal MR findings and required no further intervention. MRCP revealed abnormalities (primary sclerosing cholangitis, chronic pancreatitis, cholangitis, cholecystolithiasis or common bile duct dilation) in 10 patients, who were followed up clinically. Four patients subsequently underwent laparotomy (hepaticojejunostomy in consequence of common bile duct stenosis caused by unresectable pancreatic cancer; hepaticotomy+Kehr drainage because of insufficient biliary-enteric anastomosis; choledochojejunostomy, gastrojejunostomy and cysto-Wirsungo gastrostomy because of chronic pancreatitis, orcholedo chojejunostomy because of common bile duct stenosis caused by chronic pancreatitis). Three patients participated in therapeutic percutaneous transhepatic drainage. The indications were choledocholithiasis with choledochojejunostomy, insufficient biliary-enteric anastomosis, or cholangiocarcinoma. CONCLUSION: MRCP can assist the diagnosis and management of patients in whom ERCP is not possible.展开更多
AIM: Granuloma is considered the hallmark of microscopic diagnosis in Crohn's disease (CD), but granulomas can be detected in only 21-60% of CD patients. The aim of this studywas to evaluate the frequency of granu...AIM: Granuloma is considered the hallmark of microscopic diagnosis in Crohn's disease (CD), but granulomas can be detected in only 21-60% of CD patients. The aim of this studywas to evaluate the frequency of granulomas by multiple endoscopic biopsies in patients with CD and to examine whether group of patients with or without granuloma exhibit a different clinical course.METHODS: Fifty-six patients with newly diagnosed Cdwere included in the study. Jejunoscopy, enteroclysis and ileo-colonoscopy were performed in all patients. At least two biopsy specimens from each examined gastrointestinal segment were examined microscopically searching granuloma. The clinical course was followed in all patients, and extraintestinal manifestations as well as details of any immunosuppressive therapy and surgical intervention were noted.RESULTS: Granuloma was found in 44.6% of the cases (25 patients). Patients with granuloma had higher activity parameters at the time of the biopsies. Extraintestinal manifestations were observed and surgical interventions were performed more often in the granuloma group. The need of immunosuppressive therapy was significantly more frequent in the patients with granuloma. Granuloma formation is more often seen in younger patients, and mainly in the severe, active penetrating disease. CONCLUSION: The significantly higher frequency of surgical interventions and immunosuppressive therapy suggests that granuloma formation is associated with a more severe disease course during the first years of CD.展开更多
AIM: To explore the role of Bcl-xL and Myeloid cell leukaemia (Mcl)-1 for the apoptosis resistance of colorectal carcinoma (CRC) cells towards current treat-ment modalities. METHODS: Bcl-xL and Mcl-1 mRNA and protein ...AIM: To explore the role of Bcl-xL and Myeloid cell leukaemia (Mcl)-1 for the apoptosis resistance of colorectal carcinoma (CRC) cells towards current treat-ment modalities. METHODS: Bcl-xL and Mcl-1 mRNA and protein ex-pression were analyzed in CRC cell lines as well as human CRC tissue by Western blot,quantitative PCRand immunohistochemistry. Bcl-xL and Mcl-1 protein expression was knocked down or increased in CRC cell lines by applying specific siRNAs or expression plas-mids,respectively. After modulation of protein expres-sion,CRC cells were treated with chemotherapeutic agents,an antagonistic epidermal growth factor recep-tor (EGFR1) antibody,an EGFR1 tyrosine kinase inhibi-tor,or with the death receptor ligand TRAIL. Apoptosis induction and cell viability were analyzed. RESULTS: Here we show that in human CRC tis-sue and various CRC cell lines both Bcl-xL and Mcl-1 are expressed. Bcl-xL expression was higher in CRC tissue than in surrounding non-malignant tissue,both on protein and mRNA level. Mcl-1 mRNA expression was significantly lower in ma-lignant tissues. However,protein expression was slightly higher. Viability rates of CRC cells were significantly decreased after knock down of Bcl-xL expression,and,to a lower extent,after knock down of Mcl-1 expression. Furthermore,cells with reduced Bcl-xL or Mcl-1 expression was more sensitive towards oxaliplatin-and irinotecan-induced apoptosis,and in the case of Bcl-xL also towards 5-FU-induced apoptosis. On the other hand,upregulation of Bcl-xL by transfec-tion of an expression plasmid decreased chemothera-peutic drug-induced apoptosis. EGF treatment clearly induced Bcl-xL and Mcl-1 expression in CRC cells. Apop-tosis induction upon EGFR1 blockage by cetuximab or PD168393 was increased by inhibiting Mcl-1 and Bcl-xL expression. More strikingly,CD95-and TRAIL-induced apoptosis was increased by Bcl-xL knock down. CONCLUSION: Our data suggest that Bcl-xL and,to a lower extent,Mcl-1,are important anti-apoptotic factors in CRC. Specific downregulation of Bcl-xL is a promising approach to sensitize CRC cells towards chemotherapy and targeted therapy.展开更多
The past decade has brought substantial advances in the management of inflammatory bowel diseases(IBD). The introduction of tumor necrosis factor(TNF) antagonists, evidence for the value of combination therapy, the re...The past decade has brought substantial advances in the management of inflammatory bowel diseases(IBD). The introduction of tumor necrosis factor(TNF) antagonists, evidence for the value of combination therapy, the recog-nition of targeting lymphocyte trafficking and activation as a viable treatment, and the need for early treatment of high-risk patients are all fundamental concepts for current modern IBD treatment algorithms. In this article, authors review the existing data on approved biologicals and small molecules as well as provide insight on the current positioning of approved therapies. Patient stratification for the selection of specific therapies, therapeutic targets and patient monitoring will be discussed as well. The thera-peutic armamentarium for IBD is expanding as novel and more targeted therapies become available. In the absence of comparative trials, positioning these agents is becoming difficult. Emerging concepts for the future will include an emphasis on the development of algorithms which will facilitate a greater understanding of the positioning of novel biological drugs and small molecules in order to best tailor therapy to the patient. In the interim, anti-TNF therapy remains an important component of IBD therapy with the most real-life evidence and should be considered as first-line therapy in patients with complicated Crohn's disease and in acute-severe ulcerative colitis. The safety and efficacy of these ‘older' anti-TNF therapies can be optimized by adhering to therapeutic algorithms which combine clinical and objective markers of disease severityand response to therapy.展开更多
Inflammatory bowel disease(IBD) is a lifelong, progres-sive disease that has disabling impacts on patient's lives. Given the complex nature of the diagnosis of IBD and its management there is consequently a large ...Inflammatory bowel disease(IBD) is a lifelong, progres-sive disease that has disabling impacts on patient's lives. Given the complex nature of the diagnosis of IBD and its management there is consequently a large economic burden seen across all health care systems. Quality in-dicators(QI) have been created to assess the different fa?ades of disease management including structure, process and outcome components. Their development serves to provide a means to target and measure quality of care(Qo C). Multiple different QI sets have been published in IBD, but all serve the same purpose of trying to achieve a standard of care that can be attained on a national and international level, since there is still a major variation in clinical practice. There have been many recent innovative developments that aim to improve Qo C in IBD including telemedicine, home biomarker assessment and rapid access clinics. These are some of the novel advancements that have been shown to have great potential at improving Qo C, while offloading some of the burden that IBD can have vis-a-vis emergency room visits and hospital admissions. The aim of the current review is to summarize and discuss available QI sets and recent developments in IBD care including telemedicine, and to give insight into how the utilization of these tools could benefit the Qo C of IBD patients. Additionally, a treating-to-target structure as well as evidence surrounding aggressive management directed at tighter disease control will be presented.展开更多
AIM: To analyze the prevalence, length and predictors of hospitalization in the biological era in the populationbased inception cohort from Veszprem province.METHODS: Data of 331 incident Crohn's disease(CD) patie...AIM: To analyze the prevalence, length and predictors of hospitalization in the biological era in the populationbased inception cohort from Veszprem province.METHODS: Data of 331 incident Crohn's disease(CD) patients diagnosed between January 1, 2000 and December 31, 2010 were analyzed(median age at diagnosis: 28; IQR: 21-40 years). Both in- and outpatient records were collected and comprehensively reviewed.RESULTS: Probabilities of first CD-related hospitalization and re-hospitalization were 32.3%, 45.5%,53.7% and 13.6%, 23.9%, 29.8%, respectively after one, three and five years of follow-up in Kaplan-Meier analysis. First-year hospitalizations were related to diagnostic procedures(37%), surgery or disease activity(27% and 21%). Non-inflammatory disease behavior at diagnosis(HR = 1.32, P = 0.001) and perianal disease(HR = 1.47, P = 0.04) were associated with time to first CD-related hospitalization, while disease behavior change(HR = 2.38, P = 0.002) and need for steroids(HR = 3.14, P = 0.003) were associated with time to first re-hospitalization in multivariate analyses.Early CD-related hospitalization(within the year of diagnosis) was independently associated with need for immunosuppressives(OR = 2.08, P = 0.001) and need for surgeries(OR = 7.25, P < 0.001) during the disease course.CONCLUSION: Hospitalization and re-hospitalization rates are still high in this cohort, especially during the first-year after the diagnosis. Non-inflammatory disease behavior at diagnosis was identified as the pivotal predictive factor of both hospitalization and rehospitalization.展开更多
文摘BACKGROUND Although the usefulness of endoscopic scores,such as the Mayo Endoscopic Subscore(MES),Ulcerative Colitis Endoscopic Index of Severity(UCEIS),and Ulcerative Colitis Colonoscopic Index of Severity(UCCIS),and biomarkers such as fecal calprotectin(FC)for predicting relapse in ulcerative colitis(UC)has been reported,few studies have included endoscopic scores for evaluating the entire colon.AIM To compare the usefulness of FC value and MES,UCEIS,and UCCIS for predicting relapse in patients with UC in clinical remission.METHODS In total,75 patients with UC in clinical and endoscopic remission who visited our institution between February 2019 and March 2022 were enrolled.The diagnosis of UC was confirmed based on the clinical presentation,endoscopic findings,and histology,according to the current established criteria for UC.Fecal samples were collected the day before or after the colonoscopy for measurement of FC.Endoscopic evaluations were performed using MES,UCEIS,and UCCIS.The primary outcome measure of this study was the assessment of the association between relapse within 12 mo and MES,UCEIS,UCCIS,and FC.The secondary outcome was the comparison between endoscopic scores and biomarkers in en-rolled patients with UC with mucosal healing.RESULTSFC and UCCIS showed a significant correlation with UCEIS (r = 0.537, P < 0.001 and r = 0.957, P < 0.001, respectively).Receiver-operating characteristic analysis for predicting MES 0 showed that the area under the curve ofUCCIS was significantly higher than that of FC (P < 0.01). During the 1-year observation period, 18 (24%) patientsexperienced a relapse, and both the FC and UCCIS of the relapse group were significantly higher than that of theremission group. The cut-off values for predicting relapse were set at FC = 323 mg/kg and UCCIS = 10.2. The areaunder the curve of the receiver-operating characteristic analysis for predicting relapse did not show a significantdifference between FC and UCCIS. The accuracy of the endoscopic scores and biomarkers in predicting relapse was86.7% for UCCIS, 85.3% for UCEIS, 76.0% for FC, and 73.3% for MES.CONCLUSIONThe three endoscopic scores and FC may predict UC relapse during clinical remission. Among these scores, UCEISmay be the most useful in terms of ease of evaluation and accuracy.
文摘BACKGROUND Periodontitis has been associated with various liver diseases.However,the relevance of periodontitis in the progression of decompensated cirrhosis remains inconclusive.In particular,it is unclear whether the common periodontitis pathogens,Porphyromonas gingivalis(P.gingivalis)and Actinobacillus actinomycetemcomitans(A.actinomycetemcomitans),can be detected not only in the oral mucosa but also in ascites and stool.AIM To investigate the significance of periodontitis,P.gingivalis,and A.actinomycetemcomitans in cirrhosis patients with ascitic decompensation.METHODS This prospective study was conducted at the University Hospital Hamburg Eppendorf,a tertiary center in Northern Germany.A cohort of 27 patients with ascitic decompensated liver cirrhosis underwent dental examinations to assess the association between periodontitis and various clinical parameters of cirrhosis,as well as patient outcomes.PCR was used to test gingival samples,ascites,and stool for the presence of P.gingivalis and A.actinomycetemcomitans.Gingival samples were collected by probing the deepest gum pocket of a sextant and wiping them on a cotton swab.RESULTS Periodontitis was diagnosed in 22 out of 27(82%)ascite patients,which is significantly more common than in a control cohort of 100 unselected patients(59%,P=0.04).P.gingivalis was detected in the gingiva of six patients,and one of them also had P.gingivalis in their stool.However,P.gingivalis was not found in the ascites of any patient.Five out of six patients with P.gingivalis had periodontitis(83%).A.actinomycetemcomitans was not detected in any sample.Patients without periodontitis had a significantly higher mortality rate compared to those with periodontitis,and survival(Kaplan-Meier analysis)was longer in patients with periodontitis(P=0.02).Transplantfree survival was also more common in patients with periodontitis compared to those without(63%vs 0%,P=0.02).CONCLUSION Decompensated cirrhotic patients frequently suffer from periodontitis.However,there was no evidence of the translocation of P.gingivalis or A.actinomycetemcomitans into ascites.The survival of cirrhotic patients with periodontitis was not reduced.
基金Supported by Grant-in-aid from the Ministry of Education,Culture,Sports,Science and Technology of Japan,No.22790640 and No.24590912
文摘The cure rates of Helicobacter pylori(H.pylori)eradication therapy using a proton pump inhibitor(PPI)and antimicrobial agents such as amoxicillin,clarithromycin,and metronidazole are mainly influenced by bacterial susceptibility to antimicrobial agents and the magnitude of the inhibition of acid secretion.Annual cure rates have gradually decreased because of the increased prevalence of H.pylori strains resistant to antimicrobial agents,especially to clarithromycin.Alternative regimens have therefore been developed incorporating different antimicrobial agents.Further,standard PPI therapy(twice-daily dosing)often fails to induce a long-term increase in intragastric pH>4.0.Increasing the eradication rate requires more frequent and higher doses of PPIs.Therapeutic efficacy related to acid secretion is influenced by genetic factors such as variants of the genes encoding drug-metabolizing enzymes(e.g.,cytochrome P450 2C19,CYP2C19),drug transporters(e.g.,multidrug resistance protein-1;ABCB1),and inflammatory cytokines(e.g.,interleukin-1β).For example,quadruple daily administration of PPI therapy potently inhibits acid secretion within 24 h,irrespective of CYP2C19 genotype.Therefore,tailored H.pylori eradication regimens that address acid secretion and employ optimal antimicrobial agents based on results of antimicrobial agent-susceptibility testing may prove effective in attaining higher eradication rates.
文摘Irritable bowel syndrome(IBS)is a long-lasting,relapsing disorder characterized by abdominal pain/discomfort and altered bowel habits.Intestinal motility impairment and visceral hypersensitivity are the key factors among its multifactorial pathogenesis,both of which require effective treatment.Voltage-gated calcium channels mediate smooth muscle contraction and endocrine secretion and play important roles in neuronal transmission.Antispasmodics are a group of drugs that have been used in the treatment of IBS for decades.Alverine citrate,a spasmolytic,decreases the sensitivity of smooth muscle contractile proteins to calcium,and it is a selective 5-HT1A receptor antagonist.Alverine,in combination with simethicone,has been demonstrated to effectively reduce abdominal pain and discomfort in a large placebo-controlled trial.Mebeverine is a musculotropic agent that potently blocks intestinal peristalsis.Non-placebo-controlled trials have shown positive effects of mebeverine in IBS regarding symptom control;nevertheless,in recent placebo-controlled studies,mebeverine did not exhibit superiority over placebo.Otilonium bromide is poorly absorbed from the GI tract,where it acts locally as an L-type calcium channel blocker,an antimuscarinic and a tachykinin NK2receptor antagonist.Otilonium has effectively reduced pain and improved defecation alterations in placebocontrolled trials in IBS patients.Pinaverium bromide is also an L-type calcium channel blocker that acts locally in the GI tract.Pinaverium improves motility disorders and consequently reduces stool problems in IBS patients.Phloroglucinol and trimethylphloroglucinol are non-specific antispasmodics that reduced pain in IBS patients in a placebo-controlled trial.Antispasmodics have excellent safety profiles.T-type calcium channel blockers can abolish visceral hypersensitivity in animal models,which makes them potential candidates for the development of novel therapeutic agents in the treatment of IBS.
基金Supported by the National Research Foundation (OTKA) T30735 and T042589
文摘AIM: To assess the effect of our novel cell-permeable nuclear factor-kappaB (NF-κB) inhibitor peptide PN50 in an experimental model of acute pancreatitis. PN50 was produced by conjugating the cell-penetrating penetratin peptide with the nuclear localization signal of the NF-κB p50 subunit.METHODS: Pancreatitis was induced in male Wistar rats by administering 2×100 μg/kg body weight of cholecystokininoctapeptide (CCK) intraperitoneally (IP) at an interval of 1 h. PN50-treated animals received 1 mg/kg of PN50 IP 30 min before or after the CCK injections. The animals were sacrificed 4 h after the first injection of CCK.RESULTS: All the examined laboratory (the pancreatic weight/body weight ratio, serum amylase activity,pancreatic levels of TNF-α and IL-6, degree of lipid peroxidation, reduced glutathione levels, NF-κB binding activity, pancreatic and lung myeloperoxidase activity) and morphological parameters of the disease were improved before and after treatment with the PN50 peptide.According to the histological findings, PN50 protected the animals against acute pancreatitis by favoring the induction of apoptotic, as opposed to necrotic acinar cell death associated with severe acute pancreatitis.CONCLUSION: Our study implies that reversible inhibitors of stress-responsive transcription factors like NF-κB might be clinically useful for the suppression of the severity of acute pancreatitis.
基金Supported by The Wellcome Trust (Grant No. 022618),by the Hungarian Scientific Research Fund (D42188, T43066 and T042589)and by the GVOP-3.2.2.-2004-07-0001/3.0
文摘AIM: The sphincter of Oddi (SO) plays an important role in delivery of bile into the duodenum. To establish whether vasoactive intestinal polypeptide (VIP) and nitric oxide (NO) were involved in phasic contractile activity of the rabbit SO stimulated by cholecystokinin-octapeptide (CCK-8).METHODS: Isolated SO muscle rings were cleaned of fat and mounted horizontally on two small L-shaped hooksone of which was connected to a force transducer for the measurement of isometric tension. The experiments were carried out in a thermostatically controlled (37±0.2℃)organ bath (5 mL) containing Krebs solution. The organ fluid was gassed with 95% O2 and 50 mL/L CO2 to keep the pH at 7.40±0.05. Contractile responses to CCK-8 (1μmol/L) were evaluated in the presence and absence of N^G-nitro-L-arginine (LNNA), an inhibitor of NO synthase (100μmol/L), and (p-chloro-D-Phe^6-Leu^17)-VIP (VIPa,30μmol/L), a VIP receptor antagonist.RESULTS: CCK-8 stimulated the phasic activity of the SO.NO synthase inhibition increased the frequency and amplitude of contractions with a slight increase in developed tension.Pre-incubation with VIPa also attenuated this CCK-8 effect.The combined application of LNNA and VIPa abolished the phasic activity of the muscle rings with a marked increase in tension in response to CCK-8.CONCLUSION: VIP and NO together contribute to an increase in phasic activity of SO.
基金Supported by a Grant-in-Aid from the Japanese Ministry of Education, Culture, Sports, Science and Technology (22790640)
文摘AIM:To investigate whether potent acid inhibition is effective in non-erosive reflux disease (NERD) refractory to standard rabeprazole (RPZ) treatment. METHODS:We treated 10 Japanese patients with NERD resistant to standard dosages of RPZ:10 mg or 20 mg od,20 mg bid,or 10 mg qid for 14 d. All patients completed a frequency scale for symptoms of gastroesophageal reflux disease questionnaire frequency scale for the symptoms of GERD (FSSG); and underwent 24 h pH monitoring on day 14. RESULTS:With increased dosages and frequency of administration of RPZ,median intragastric pH significantly increased,and FSSG scores significantly decreased. With RPZ 10 mg qid,potent acid inhibition was attained throughout 24 h. However,five subjects were refractory to RPZ 10 mg qid,although the median intragastric pH in these subjects (6.6,range:6.2-7.1) was similar to that in the remaining five responsive subjects (6.5,range:5.3-7.3). With baseline RPZ 10 mg od,FSSG scores in responsive patients improved by > 30%,whereas there was no significant decrease in the resistant group. CONCLUSION:NERD patients whose FSSG score fails to decrease by > 30% after treatment with RPZ 10 mg od for 14 d are refractory to higher dosage.
基金Supported by Research grants from Merck KGaA,Darmstadt,Germany,to Schulze-Bergkamen H
文摘AIM:To analyze the effect of chemotherapeutic drugs and specific kinase inhibitors,in combination with the death receptor ligand tumor necrosis factor-related apoptosis inducing ligand(TRAIL),on overcoming TRAIL resistance in hepatocellular carcinoma(HCC)and to study the efficacy of agonistic TRAIL antibodies,as well as the commitment of antiapoptotic BCL-2 proteins, in TRAIL-induced apoptosis. METHODS:Surface expression of TRAIL receptors (TRAIL-R1-4)and expression levels of the antiapoptotic BCL-2 proteins MCL-1 and BCL-xL were analyzed by flow cytometry and Western blotting,respectively. Knock-down of MCL-1 and BCL-xL was performed by transfecting specific small interfering RNAs.HCC cellswere treated with kinase inhibitors and chemotherapeutic drugs.Apoptosis induction and cell viability were analyzed via flow cytometry and 3-(4,5-Dimethyl-thiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. RESULTS:TRAIL-R1 and-R2 were profoundly expressed on the HCC cell lines Huh7 and Hep-G2. However,treatment of Huh7 and Hep-G2 with TRAIL and agonistic antibodies only induced minor apoptosis rates.Apoptosis resistance towards TRAIL could be considerably reduced by adding the chemotherapeutic drugs 5-fluorouracil and doxorubicin as well as the kinase inhibitors LY294002[inhibition of phosphoinositol- 3-kinase(PI3K)],AG1478(epidermal growth factor receptor kinase),PD98059(MEK1),rapamycin(mam- malian target of rapamycin)and the multi-kinase inhibitor Sorafenib.Furthermore,the antiapoptotic BCL-2 proteins MCL-1 and BCL-xL play a major role in TRAIL resistance:knock-down by RNA interference increased TRAIL-induced apoptosis of HCC cells.Additionally, knock-down of MCL-1 and BCL-xL led to a significant sensitization of HCC cells towards inhibition of both c-Jun N-terminal kinase and PI3K.CONCLUSION:Our data identify the blockage of survival kinases,combination with chemotherapeutic drugs and targeting of antiapoptotic BCL-2 proteins as promising ways to overcome TRAIL resistance in HCC.
基金Supported by the Danish patient society of inflammatory bowel disease and irritable bowel syndrome patients,Colitis Crohn Foreningen
文摘AIM: To investigate patient-reported outcomes from, and adherence to, a low FODMAP diet among patients suffering from irritable bowel syndrome and inflammatory bowel disease.METHODS: Consecutive patients with irritable bowel syndrome(IBS) or inflammatory bowel disease(IBD) and co-existing IBS fulfilling the ROME Ⅲ criteria, who previously attended an outpatient clinic for low FODMAP diet(LFD) dietary management and assessment by a gastroenterologist, were invited to participate in a retrospective questionnaire analysis. The questionnaires were sent and returned by regular mail and gathered information on recall of dietarytreatment, efficacy, symptoms, adherence, satisfaction, change in disease course and stool type, and quality of life. Before study enrolment all patients had to sign an informed written consent.RESULTS: One hundred and eighty patients were included, 131(73%) IBS and 49(27%) IBD patients. Median age was 43 years(range: 18-85) and 147(82%) were females. Median follow-up time was 16 mo(range: 2-80). Eighty-six percent reported either partial(54%) or full(32%) efficacy with greatest improvement of bloating(82%) and abdominal pain(71%). The proportion of patients with full efficacy tended to be greater in the IBD group than in the IBS group(42% vs 29%, P = 0.08). There was a significant reduction in patients with a chronic continuous disease course in both the IBS group(25%, P < 0.001) and IBD group(23%, P = 0.002) along with a significant increase in patients with a mild indolent disease course of 37%(P < 0.001) and 23%(P = 0.002), respectively. The proportion of patients having normal stools increased with 41% in the IBS group(P < 0.001) and 66% in the IBD group(P < 0.001). One-third of patients adhered to the diet and high adherence was associated with longer duration of dietary course(P < 0.001). Satisfaction with dietary management was seen in 83(70%) IBS patients and 24(55%) IBD patients. Eightyfour percent of patients lived on a modified LFD, where some foods rich in FODMAPs were reintroduced, and 16% followed the LFD by the book without deviations. Wheat, dairy products, and onions were the foods most often not reintroduced by patients.CONCLUSION: These data suggest that a diet low in FODMAPs is an efficacious treatment solution in the management of functional bowel symptoms for IBS and IBD patients.
基金the Hungarian Scientific Research Fund,No.K116634 to Hegyi Pthe Momentum Grant of the Hungarian Academy of Sciences,No.LP2014-10/2014 to Hegyi P
文摘Acute pancreatitis (AP) is a serious inflammatory disease with rising incidence both in the adult and pediatric populations. It has been shown that mitochondrial injury and energy depletion are the earliest intracellular events in the early phase of AP. Moreover, it has been revealed that restoration of intracellular ATP level restores cellular functions and defends the cells from death. We have recently shown in a systematic review and meta-analysis that early enteral feeding is beneficial in adults; however, no reviews are available concerning the effect of early enteral feeding in pediatric AP. In this minireview, our aim was to systematically analyse the literature on the treatmentof acute pediatric pancreatitis. The preferred reporting items for systematic review(PRISMA-P) were followed, and the question was drafted based on participants, intervention, comparison and outcomes: P: patients under the age of twenty-one suffering from acute pancreatitis; I: early enteral nutrition (per os and nasogastric- or nasojejunal tube started within 48 h); C: nil per os therapy; O: length of hospitalization, need for treatment at an intensive care unit, development of severe AP, lung injury (including lung oedema and pleural effusion), white blood cell count and pain score on admission. Altogether, 632 articles (Pub Med: 131; EMBASE: 501) were found. After detailed screening of eligible papers, five of them met inclusion criteria. Only retrospective clinical trials were available. Due to insufficient information from the authors, it was only possible to address length of hospitalization as an outcome of the study. Our mini-meta-analysis showed that early enteral nutrition significantly(SD = 0.806, P = 0.034) decreases length of hospitalization compared with nil per os diet in acute pediatric pancreatitis. In this minireview, we clearly show that early enteral nutrition, started within 24-48 h, is beneficial in acute pediatric pancreatitis. Prospective studies and better presentation of research are crucially needed to achieve a higher level of evidence.
文摘BACKGROUND Epidemiologic studies have revealed a decrease in the prevalence of Helicobacter pylori(H.pylori)infection in Western Europe.AIM To obtain data regarding the prevalence of H.pylori in Csongrád and Békés Counties in Hungary,evaluate the differences in its prevalence between urban and rural areas,and establish factors associated with positive seroprevalence.METHODS One-thousand and one healthy blood donors[male/female:501/500,mean age:40(19–65)years]were enrolled in this study.Subjects were tested for H.pylori IgG antibody positivity via enzyme-linked immunosorbent assay.Subgroup analysis by age,gender,smoking habits,alcohol consumption,and urban vs nonurban residence was also performed.RESULTS The overall seropositivity of H.pylori was 32%.It was higher in males(34.93%vs 29.2%,P=0.0521)and in rural areas(36.2%vs 27.94%,P=0.0051).Agricultural/industrial workers were more likely to be positive for infection than office workers(38.35%vs 30.11%,P=0.0095)and rural subjects in Békés County than those in Csongrád County(43.36%vs 33.33%,P=0.0015).CONCLUSION Although the prevalence of H.pylori infection decreased in recent decades in Southeast Hungary,it remains high in middle-aged rural populations.Generally accepted risk factors for H.pylori positivity appeared to be valid for the studied population.
文摘AIM: To explore the propriety of providing hepatitis B virus(HBV) genotypes F and H with two distinct genotypes.METHODS: Eleven HBV isolates of genotype F (HBV/F)were recovered from patients living in San Francisco,Japan, Panama, and Venezuela, and their full-length sequences were determined. Phylogenetic analysis was carried out among them along with HBV isolates previously reported.RESULTS: Seven of them clustered with reported HBV/F isolates in the phylogenetic tree constructed on the entire genomic sequence. The remaining four flocked on another branch along with three HBV isolates formerly reported as genotype H. These seven HBV isolates, including the four in this study and the three reported, had a sequence divergence of 7.3-9.5% from the other HBV/F isolates,and differed by ＞ 13.7% from HBV isolates of the other six genotypes (A-E and G). Based on a marked genomic divergence, falling just short of ＞8% separating the seven genotypes, these seven HBV/F isolates were classified into F2 subtype and the former seven into F1 subtype provisionally. In a pairwise comparison of the S-gene sequences among the 7 HBV/F2 isolates and against 47HBV/F1 isolates as well as 136 representing the other six genotypes (A-E and G), two clusters separated by distinct genetic distances emerged.CONCLUSION: Based on these analyses, classifying HBV/F isolates into two subtypes (F1 and F2) would be more appropriate than providing them with two distinct genotypes (F and H).
文摘Ultrasound is an undervalued non-invasive examination in the diagnosis of colonic diseases. It has been replaced by the considerably more expensive magnetic resonance imaging and computed tomography, despite the fact that, as first examination, it can usefully supplement the diagnostic process. Transabdominal ultrasound can provide quick information about bowel status and help in the choice of adequate further examinations and treatment. Ultrasonography,as a screening imaging modality in asymptomatic patients can identify several colonic diseases such as diverticulosis, inflammatory bowel disease or cancer. In addition, it is widely available, cheap, non-invasive technique without the use of ionizing radiation, therefore it is safe to use in childhood or during pregnancy, and can be repeated at any time. New ultrasound techniques such as elastography, contrast enhanced and Doppler ultrasound, miniprobes rectal and transperineal ultrasonography have broadened the indication. It gives an overview of the methodology of various ultrasound examinations, presents the morphology of normal bowel wall and the typical changes in different colonic diseases. We will pay particular attention to rectal and transperineal ultrasound because of their outstanding significance in the diagnosis of rectal and perineal disorders. This article seeks to overview the diagnostic impact and correct indications of bowel ultrasound.
基金Supported by Grants OTKA-76316,OTKA-K81117,and ETT-028-02 (Veres G and Vannay á are holders of the János Bolyai Research grant)János Bolyai Research Scholarship of the Hungarian Academy of Sciences
文摘AIM:To investigate intestinal alkaline phosphatase(iAP) in the intestinal mucosa of children with inflammatory bowel disease(IBD).METHODS:Colonic biopsy samples were taken from 15 newly diagnosed IBD patients and from 10 healthy controls.In IBD patients,specimens were obtainedboth from inflamed and non-inflamed areas.The iAP mRNA and protein expression was determined by reverse transcription-polymerase chain reaction and Western blotting analysis,respectively.Tissue localization of iAP and Toll-like receptor(TLR) 4 was investigated by immunofluorescent staining.RESULTS:The iAP protein level in the inflamed mucosa of children with Crohn's disease(CD) and ulcerative colitis(UC) was significantly decreased when compared with controls(both P < 0.05).Similarly,we found a significantly decreased level of iAP protein in the inflamed mucosa in CD compared with non-inflamed mucosa in CD(P < 0.05).In addition,the iAP protein level in inflamed colonic mucosa in patients with UC was decreased compared with non-inflamed mucosa in patients with CD(P < 0.05).iAP protein levels in the non-inflamed mucosa of patients with CD were similar to controls.iAP mRNA expression in inflamed colonic mucosa of children with CD and UC was not significantly different from that in non-inflamed colonic mucosa with CD.Expression of iAP mRNA in patients with noninflamed mucosa and in controls were similar.Co-localization of iAP with TLR4 showed intense staining with a dotted-like pattern.iAP was present in the inflamed and non-inflamed mucosa of patients with CD,UC,and in control biopsy specimens,irrespective of whether it was present in the terminal ileum or in the colon.However,the fluorescent signal of TLR4 was more pronounced in the colon compared with the terminal ileum in all groups studied.CONCLUSION:Lower than normal iAP protein levels in inflamed mucosa of IBD patients may indicate a role for iAP in inflammatory lesions in IBD.Based on our results,administration of exogenous iAP enzyme to patients with the active form of IBD may be a therapeutic option.
基金Supported by the ETT 5K503 and the Hungarian Academy of Sciences,B 5/2003
文摘AIM: To evaluate the value of MR cholangiopancreatography (MRCP) in patients in whom endoscopic retrograde cholangiopancreatography (ERCP) was unsuccessfully performed by experts in a tertiary center. METHODS: From January 2000 to June 2003, 22 patients fulfilled the inclusion criteria. The indications for ERCP were obstructive jaundice (n = 9), abnormal liver enzymes (n=8),suspected chronic pancreatitis (n = 2), recurrent acute pancreatitis (n = 2), or suspected pancreatic cancer (n=1). The reasons for the ERCP failure were the postsurgical anatomy (n = 7), duodenal stenosis (n = 3), duodenal diverticulum (n = 2), and technical failure (n = 10). MRCP images were evaluated before and 5 and 10 min after i.v. administration of 0.5 IU/kg secretin.RESULTS: The MRCP images were diagnosed in all 21patients. Five patients gave normal MR findings and required no further intervention. MRCP revealed abnormalities (primary sclerosing cholangitis, chronic pancreatitis, cholangitis, cholecystolithiasis or common bile duct dilation) in 10 patients, who were followed up clinically. Four patients subsequently underwent laparotomy (hepaticojejunostomy in consequence of common bile duct stenosis caused by unresectable pancreatic cancer; hepaticotomy+Kehr drainage because of insufficient biliary-enteric anastomosis; choledochojejunostomy, gastrojejunostomy and cysto-Wirsungo gastrostomy because of chronic pancreatitis, orcholedo chojejunostomy because of common bile duct stenosis caused by chronic pancreatitis). Three patients participated in therapeutic percutaneous transhepatic drainage. The indications were choledocholithiasis with choledochojejunostomy, insufficient biliary-enteric anastomosis, or cholangiocarcinoma. CONCLUSION: MRCP can assist the diagnosis and management of patients in whom ERCP is not possible.
文摘AIM: Granuloma is considered the hallmark of microscopic diagnosis in Crohn's disease (CD), but granulomas can be detected in only 21-60% of CD patients. The aim of this studywas to evaluate the frequency of granulomas by multiple endoscopic biopsies in patients with CD and to examine whether group of patients with or without granuloma exhibit a different clinical course.METHODS: Fifty-six patients with newly diagnosed Cdwere included in the study. Jejunoscopy, enteroclysis and ileo-colonoscopy were performed in all patients. At least two biopsy specimens from each examined gastrointestinal segment were examined microscopically searching granuloma. The clinical course was followed in all patients, and extraintestinal manifestations as well as details of any immunosuppressive therapy and surgical intervention were noted.RESULTS: Granuloma was found in 44.6% of the cases (25 patients). Patients with granuloma had higher activity parameters at the time of the biopsies. Extraintestinal manifestations were observed and surgical interventions were performed more often in the granuloma group. The need of immunosuppressive therapy was significantly more frequent in the patients with granuloma. Granuloma formation is more often seen in younger patients, and mainly in the severe, active penetrating disease. CONCLUSION: The significantly higher frequency of surgical interventions and immunosuppressive therapy suggests that granuloma formation is associated with a more severe disease course during the first years of CD.
基金A Research Grant of Merck Pharma GmbH,Darmstadt,Germany,to the University Clinic of Mainz
文摘AIM: To explore the role of Bcl-xL and Myeloid cell leukaemia (Mcl)-1 for the apoptosis resistance of colorectal carcinoma (CRC) cells towards current treat-ment modalities. METHODS: Bcl-xL and Mcl-1 mRNA and protein ex-pression were analyzed in CRC cell lines as well as human CRC tissue by Western blot,quantitative PCRand immunohistochemistry. Bcl-xL and Mcl-1 protein expression was knocked down or increased in CRC cell lines by applying specific siRNAs or expression plas-mids,respectively. After modulation of protein expres-sion,CRC cells were treated with chemotherapeutic agents,an antagonistic epidermal growth factor recep-tor (EGFR1) antibody,an EGFR1 tyrosine kinase inhibi-tor,or with the death receptor ligand TRAIL. Apoptosis induction and cell viability were analyzed. RESULTS: Here we show that in human CRC tis-sue and various CRC cell lines both Bcl-xL and Mcl-1 are expressed. Bcl-xL expression was higher in CRC tissue than in surrounding non-malignant tissue,both on protein and mRNA level. Mcl-1 mRNA expression was significantly lower in ma-lignant tissues. However,protein expression was slightly higher. Viability rates of CRC cells were significantly decreased after knock down of Bcl-xL expression,and,to a lower extent,after knock down of Mcl-1 expression. Furthermore,cells with reduced Bcl-xL or Mcl-1 expression was more sensitive towards oxaliplatin-and irinotecan-induced apoptosis,and in the case of Bcl-xL also towards 5-FU-induced apoptosis. On the other hand,upregulation of Bcl-xL by transfec-tion of an expression plasmid decreased chemothera-peutic drug-induced apoptosis. EGF treatment clearly induced Bcl-xL and Mcl-1 expression in CRC cells. Apop-tosis induction upon EGFR1 blockage by cetuximab or PD168393 was increased by inhibiting Mcl-1 and Bcl-xL expression. More strikingly,CD95-and TRAIL-induced apoptosis was increased by Bcl-xL knock down. CONCLUSION: Our data suggest that Bcl-xL and,to a lower extent,Mcl-1,are important anti-apoptotic factors in CRC. Specific downregulation of Bcl-xL is a promising approach to sensitize CRC cells towards chemotherapy and targeted therapy.
文摘The past decade has brought substantial advances in the management of inflammatory bowel diseases(IBD). The introduction of tumor necrosis factor(TNF) antagonists, evidence for the value of combination therapy, the recog-nition of targeting lymphocyte trafficking and activation as a viable treatment, and the need for early treatment of high-risk patients are all fundamental concepts for current modern IBD treatment algorithms. In this article, authors review the existing data on approved biologicals and small molecules as well as provide insight on the current positioning of approved therapies. Patient stratification for the selection of specific therapies, therapeutic targets and patient monitoring will be discussed as well. The thera-peutic armamentarium for IBD is expanding as novel and more targeted therapies become available. In the absence of comparative trials, positioning these agents is becoming difficult. Emerging concepts for the future will include an emphasis on the development of algorithms which will facilitate a greater understanding of the positioning of novel biological drugs and small molecules in order to best tailor therapy to the patient. In the interim, anti-TNF therapy remains an important component of IBD therapy with the most real-life evidence and should be considered as first-line therapy in patients with complicated Crohn's disease and in acute-severe ulcerative colitis. The safety and efficacy of these ‘older' anti-TNF therapies can be optimized by adhering to therapeutic algorithms which combine clinical and objective markers of disease severityand response to therapy.
文摘Inflammatory bowel disease(IBD) is a lifelong, progres-sive disease that has disabling impacts on patient's lives. Given the complex nature of the diagnosis of IBD and its management there is consequently a large economic burden seen across all health care systems. Quality in-dicators(QI) have been created to assess the different fa?ades of disease management including structure, process and outcome components. Their development serves to provide a means to target and measure quality of care(Qo C). Multiple different QI sets have been published in IBD, but all serve the same purpose of trying to achieve a standard of care that can be attained on a national and international level, since there is still a major variation in clinical practice. There have been many recent innovative developments that aim to improve Qo C in IBD including telemedicine, home biomarker assessment and rapid access clinics. These are some of the novel advancements that have been shown to have great potential at improving Qo C, while offloading some of the burden that IBD can have vis-a-vis emergency room visits and hospital admissions. The aim of the current review is to summarize and discuss available QI sets and recent developments in IBD care including telemedicine, and to give insight into how the utilization of these tools could benefit the Qo C of IBD patients. Additionally, a treating-to-target structure as well as evidence surrounding aggressive management directed at tighter disease control will be presented.
文摘AIM: To analyze the prevalence, length and predictors of hospitalization in the biological era in the populationbased inception cohort from Veszprem province.METHODS: Data of 331 incident Crohn's disease(CD) patients diagnosed between January 1, 2000 and December 31, 2010 were analyzed(median age at diagnosis: 28; IQR: 21-40 years). Both in- and outpatient records were collected and comprehensively reviewed.RESULTS: Probabilities of first CD-related hospitalization and re-hospitalization were 32.3%, 45.5%,53.7% and 13.6%, 23.9%, 29.8%, respectively after one, three and five years of follow-up in Kaplan-Meier analysis. First-year hospitalizations were related to diagnostic procedures(37%), surgery or disease activity(27% and 21%). Non-inflammatory disease behavior at diagnosis(HR = 1.32, P = 0.001) and perianal disease(HR = 1.47, P = 0.04) were associated with time to first CD-related hospitalization, while disease behavior change(HR = 2.38, P = 0.002) and need for steroids(HR = 3.14, P = 0.003) were associated with time to first re-hospitalization in multivariate analyses.Early CD-related hospitalization(within the year of diagnosis) was independently associated with need for immunosuppressives(OR = 2.08, P = 0.001) and need for surgeries(OR = 7.25, P < 0.001) during the disease course.CONCLUSION: Hospitalization and re-hospitalization rates are still high in this cohort, especially during the first-year after the diagnosis. Non-inflammatory disease behavior at diagnosis was identified as the pivotal predictive factor of both hospitalization and rehospitalization.
