bluuebunny/crossref_metadata_2025 huggingface dataset:
Predictors of outcome in patients with unresectable hepatocellular carcinoma receiving transcatheter arterial chemoembolization
Authors: SHEN H. , AGARWAL D. , QI R. , CHALASANI N. , LIANGPUNSAKUL S. , LUMENG L. , YOO H. , KWO P.
Published: July 2010

Background  Transcatheter arterial chemoembolization (TACE) has been shown to improve survival in patients with unresectable hepatocellular carcinoma (HCC).

Aim  To identify pretreatment factors that predicts increased mortality in HCC patients receiving TACE.

Methods  Retrospective review of all patients who underwent TACE for HCC from January 1999 to November 2004. Patient demographics, aetiology of liver disease, laboratory and imaging data regarding tumour characteristics were obtained.

Results  Eighty‐eight patients (57 ± 1 years age) received 1–4 sessions of TACE (1.4 ± 0.1). Tumour size was 3.3 ± 0.2 cm (range 1–13 cm, median 3 cm) with mean number of lesions 1.9 ± 0.1 (range 1–7). Mean model for the end stage liver disease score: 11 ± 0.4; cancer of the liver Italian program score: 1.3 ± 0.1. Survival post‐TACE (excluding those underwent orthotopic liver transplantation) was 12 ± 0.3 months. By multivariate analysis, tumour size (HR = 1.37, 95% CI: 1.11–1.68, P = 0.003), hypovascularity (HR = 12.62, 95% CI: 1.79–88.92, P = 0.01) and elevated international normalized ratio (HR = 1.46, 95% CI: 1.10–1.92 P = 0.008) are shown to be significant risk factors for increased mortality.

Conclusion  TACE therapy leads to a mean survival of 12 months in patients not receiving orthotopic liver transplantation. Tumour size, hypovascularity on imaging, and elevated international normalized ratio are predictors of increased mortality after TACE therapy for HCC.
Effect of long‐term treatment with octreotide on rectal sensitivity in patients with non‐constipated irritable bowel syndrome
Authors: KLOOKER T. K. , KUIKEN S. D. , LEI A. , BOECKXSTAENS G. E.
Published: July 2010

Background Acute administration of octreotide reduces visceral perception and therefore has been suggested as potential treatment for irritable bowel syndrome. Whether prolonged treatment with octreotide also reduces visceral sensitivity and improves gastrointestinal symptoms remains, however, unknown.

Aim To investigate the effect of a slow release preparation of octreotide on rectal sensitivity and symptoms in irritable bowel syndrome patients.

Methods Forty‐six non‐constipated irritable bowel syndrome patients (52% female, 19–63 years) participated. Before and after 8 weeks of treatment with octreotide (Sandostatin LAR 20 mg i.m.) or placebo, patients underwent a barostat study to assess the rectal sensitivity. During a 2‐week run‐in period and treatment, abdominal pain, defecation frequency, consistency and symptom relief were scored weekly.

Results Octreotide, but not placebo, significantly increased the threshold for first sensation. Thresholds for urge to defecate and discomfort/pain and rectal compliance were not altered by either treatment. Octreotide improved stool consistency compared with placebo (loose stools after eight weeks: octreotide: 52%, placebo: 81%,P < 0.05). In contrast, abdominal pain and defecation frequency were not affected.

Conclusions Although the threshold of first rectal sensation increased and stool consistency improved, long‐term treatment with octreotide, at least at the current dose used, has no visceral analgesic effect and fails to improve irritable bowel syndrome symptoms.
An open population screening study for HFE gene major mutations proves the low prevalence of C282Y mutation in Central Italy
Authors: FLOREANI A. , RIZZOTTO E. ROSA , BASSO D. , NAVAGLIA F. , ZANINOTTO M. , PETRIDIS I. , DI ANDREA O. , TESTA R. , MARRA M. , BALDO V. , CHIARAMONTE M. ,   ARSITA‐TWO RESEARCH GROUP
Published: July 2010

Background  The C282Y mutation in the HFE gene is responsible for most cases of hereditary haemochromatosis.

Aim  To investigate the allele frequency of HFE mutations and the associations between mutations and cases of iron overload or liver diseases in an open population of Central Italy.

Methods  A total of 502 individuals over 8 years of age, comprising 203 males and 299 females, who were residents in Arsita (a small town in Central Italy), were assayed for: C282Y, H63D and S65C mutations of the HFE gene by TaqMan probes; body mass index, serum ferritin, transferrin saturation, transaminases, GGT, glucose, insulin, total cholesterol, high‐density lipoprotein cholesterol, low‐density lipoprotein cholesterol, triglycerides, HBV and HCV serum markers. Information was obtained on alcohol intake. Liver ultrasound was performed in 334 (67%) subjects.

Results  The allele frequencies for C282Y, H63D and S65C were 2%, 15%, and 0.01%, respectively. C282Y/wt was found in 19 subjects (4%), H63D/wt in 127 (25%), H63D/H63D in 11 (2%) and S65C/wt in one (2.0‰). No homozygosity for C282Y or compound mutation (C282Y/H63D) was found in the study population, but 27 subjects (5%) had TfSat >45% (including 10 subjects with high serum ferritin). Overall, 49 subjects (9.8%) were HCV‐RNA‐positive. Logistic regression analysis indicated that male gender (P = 0.000) and hepatic steatosis (P = 0.017) were independent variables correlating to a high serum ferritin.

Conclusion  C282Y HFE mutation is less frequent in Central Italy than in Northern Italy.
Reverse transcriptase activity in patients with primary biliary cirrhosis and other autoimmune liver disorders
Authors: MCDERMID J. , CHEN M. , LI Y. , WASILENKO S. , BINTNER J. , MCDOUGALL C. , PANG X. , BAIN V. G. , MASON A. L.
Published: July 2010

Background  Patients with biliary disease make retroviral antibodies and the Human Betaretrovirus has been characterized in patients with primary biliary cirrhosis.

Aim  To screen patients with autoimmune liver disease for evidence of retroviral infection.

Methods  Real‐time reverse transcriptase polymerase chain reaction was used to detect Human Betaretrovirus, and a reverse transcriptase assay to measure reverse transcriptase activity in plasma.

Results  Using reverse transcriptase polymerase chain reaction, 24% of primary biliary cirrhosis samples were positive for Human Betaretrovirus when compared to 13% with autoimmune hepatitis, 5% of other liver diseases and 3% of the non‐liver disease control subjects. Reverse transcriptase activity was found in 73% of patients with autoimmune hepatitis, 42% with primary biliary cirrhosis, 22% of liver patients without viral or autoimmune disease and 7% of subjects without liver disease. In patients with autoimmune liver disease, detection of reverse transcriptase activity was related to higher ALT levels, whereas others stabilized on immunosuppressive therapy either preliver or postliver transplantation were less likely to be reverse transcriptase‐positive.

Conclusions  Most patients with autoimmune hepatitis have detectable reverse transcriptase activity. Investigations will be required to assess whether this represents the expression of endogenous retroviruses and retrotransposable elements in inflamed tissue, or signifies the presence of exogenous retroviral infection.
One‐week acid suppression trial in uninvestigated dyspepsia patients with epigastric pain or burning to predict response to 8 weeks’ treatment with esomeprazole: a randomized, placebo‐controlled study
Authors: VAN ZANTEN S. V. , FLOOK N. , TALLEY N. J. , VAKIL N. , LAURITSEN K. , BOLLING‐STERNEVALD E. , PERSSON T. , BJÖRCK E. , SVEDBERG L.‐E. ,   ON BEHALF OF THE STARS II STUDY GROUP
Published: July 2010

Background

While empiric acid‐suppressive therapy for uninvestigated dyspepsia patients with symptoms of epigastric pain or burning is standard practice, it is unknown whether an early response to therapy predicts outcome.

Aim

To evaluate whether a 1‐w acid suppression trial is effective for predicting 8‐w response in such patients.

Methods

Helicobacter pylori‐negative patients (aged 18–50 years) in primary care with uninvestigated epigastric pain or burning were randomized to esomeprazole 40 mg q.d.s. or b.d. for 1w, followed by esomeprazole 40 mg q.d.s. or placebo for 7w. Each day, patients rated the severity of their symptoms.

Results

Based on the last 3d, 1‐w response rates were 39% (231 of 588) and 43% (258 of 596) with esomeprazole 40 mg q.d.s. and b.d., respectively. Based on the last 7d, response rates at 4w were 38% (283 of 738) and 25% (93 of 380) for esomeprazole and placebo, respectively, and 47% (339 of 716) and 34% (124 of 368), respectively, at 8w (both P < 0.001 vs. placebo). The sensitivity and specificity of esomeprazole treatment were 58% and 70%, respectively, at 8w.

Conclusion

A 1‐w acid suppression trial is of limited clinical value for predicting 8‐w response in patients with symptoms of epigastric pain or burning. Esomeprazole provides greater symptom control than placebo at 4w and 8w.
The safety, tolerance, pharmacokinetic and pharmacodynamic effects of single doses of AT‐1001 in coeliac disease subjects: a proof of concept study
Authors: PATERSON B. M. , LAMMERS K. M. , ARRIETA M. C. , FASANO A. , MEDDINGS J. B.
Published: July 2010

Background

Lifelong adherence to a strict gluten‐free diet is the cornerstone of coeliac disease treatment. Elucidation of disease pathogenesis has created opportunities for novel therapeutic approaches to coeliac disease. AT‐1001 is an inhibitor of paracellular permeability whose structure is derived from a protein secreted by Vibrio cholerae.

Aim

To determine the safety and tolerability of 12 mg doses of AT‐1001 in coeliac disease subjects challenged with gluten.

Methods

An in‐patient, double‐blind, randomized placebo‐controlled safety study utilizing intestinal permeability, measured via fractional excretions of lactulose and mannitol, as an exploratory measure of drug efficacy.

Results

Compared to placebo, no increase in adverse events occurred in patients exposed to AT‐1001. Following acute gluten exposure, a 70% increase in intestinal permeability was detected in the placebo group, while none was seen in the AT‐1001 group. Interferon‐γ levels increased in four of seven patients (57%) of the placebo group, but only in four of 14 patients (29%) of the AT‐1001 group. Gastrointestinal symptoms were more frequently detected in the placebo group when compared to the AT‐1001 group (P = 0.018).

Conclusions

AT‐1001 is well tolerated and appears to reduce intestinal barrier dysfunction, proinflammatory cytokine production, and gastrointestinal symptoms in coeliacs after gluten exposure.
Infliximab in severe ulcerative colitis: short‐term results of different infusion regimens and long‐term follow‐up
Authors: KOHN A. , DAPERNO M. , ARMUZZI A. , CAPPELLO M. , BIANCONE L. , ORLANDO A. , VISCIDO A. , ANNESE V. , RIEGLER G. , MEUCCI G. , MARROLLO M. , SOSTEGNI R. , GASBARRINI A. , PERALTA S. , PRANTERA C.
Published: July 2010

Background

Severe ulcerative colitis is a life‐threatening disorder, despite i.v. glucocorticoids treatment. Infliximab has been proposed as a safe rescue therapy.

Aim

To evaluate short‐ and long‐term effectiveness and safety of infliximab in severe refractory ulcerative colitis.

Methods

Eighty‐three patients with severe ulcerative colitis (i.v. glucocorticoids treatment‐refractory) were treated with infliximab in 10 Italian Gastroenterology Units. Patients underwent one or more infusions according to the choice of treating physicians. Short‐term outcome was colectomy/death 2 months after the first infusion. Long‐term outcome was survival free from colectomy. Safety data were recorded.

Results

Twelve patients (15%) underwent colectomy within 2 months. One died of Legionella pneumophila infection 12 days after infliximab. Early colectomy rates were higher in patients receiving one infusion (9/26), compared with those receiving two/more infusions (3/57, P = 0.001, OR = 9.53).

Seventy patients who survived colectomy and did not experience any fatal complications were followed‐up for a median time of 23 months; 58 patients avoided colectomy during the follow‐up. Forty‐two patients were maintained on immunosuppressive drugs. No clinical features were associated with outcomes.

Conclusions

Infliximab is an effective and relatively safe therapy to avoid colectomy and maintain long‐term remission for patients with severe refractory ulcerative colitis. In the short term, two or more infusions seem to be more effective than one single infusion.
Long‐term survival of patients with unresectable hepatocellular carcinoma treated with transcatheter arterial chemoinfusion
Authors: HA B. Y. , AHMED A. , SZE D. Y. , RAZAVI M. K. , SIMPSON N. , KEEFFE E. B. , NGUYEN M. H.
Published: July 2010

Background

Transcatheter arterial chemoembolization (TACE) has become one of the most common treatments for unresectable hepatocellular carcinoma. Published studies of TACE report a 5–16% risk of serious complications. Compared with TACE, transcatheter arterial chemoinfusion (TACI) may have similar efficacy and fewer side effects.

Aim

To examine the clinical outcomes of TACI.

Methods

We performed a retrospective cohort study of 345 consecutive TACI cases in 165 patients performed at a single United States medical center between 1998 and 2002. Primary outcomes were tumour response and survival rates.

Results

Only seven patients were hospitalized for more than 24 h after the procedure, and only three patients had worsening of liver function within 30 days of TACI. Survival was significantly poorer for patients with tumour‐node‐metastasis (TNM) IV compared to those with TNM I–III and also for patients with Child’s class B/C vs. A. Following adjustment for age, gender, ethnicity and aetiology of liver diseases, independent predictors of poor survival were Child’s class B/C [Hazard Ratio (HR) = 1.69, P = 0.024] and TNM IV staging (HR = 1.63, P = 0.014).

Conclusions

TACI appears to be safe and effective for unresectable hepatocellular carcinoma with TNM stage I–III; randomized controlled trials are needed to compare TACI to TACE.
Epidemiology of chronic atrophic gastritis: population‐based study among 9444 older adults from Germany
Authors: WECK M. N. , STEGMAIER C. , ROTHENBACHER D. , BRENNER H.
Published: July 2010

Background

Epidemiological data on chronic atrophic gastritis from general population samples are sparse in Germany.

Aim

To assess prevalence of chronic atrophic gastritis according to potential risk factors and clinical outcomes in a large‐scale population‐based study.

Methods

In the baseline examination of ESTHER, a population‐based cohort study conducted in Germany, serological measurements of pepsinogen (PG) I and II and Helicobacter pylori antibodies were taken in 9444 women and men aged 50–74 years. Information on potential risk factors and medical history were obtained by questionnaire.

Results

With the definition used in the EUROGAST study (PG I < 25 ng/mL), prevalence of chronic atrophic gastritis increased from 4.8% in age group 50–54 to 8.7% in age group 70–74. An alternative definition of chronic atrophic gastritis (PG I < 70 ng/mL and PG I/PG II < 3), used in multiple studies from Japan, revealed a greater increase with age (from 2.7% to 9.1%) and a strong association with H. pylori infection (adjusted odds ratio: 2.9, 95% confidence interval: 2.4–3.7). With both definitions, a strong inverse association with heartburn was observed.

Conclusions

Overall chronic atrophic gastritis prevalence is low among older adults in Germany, but it strongly increases with age and H. pylori infection.
Meta‐analysis: enteral nutrition in active Crohn’s disease in children
Authors: DZIECHCIARZ P. , HORVATH A. , SHAMIR R. , SZAJEWSKA H.
Published: July 2010

Background

Controversy exists surrounding the optimal treatment for inducing remission in active Crohn’s disease.

Aim

To review and update evidence on the effectiveness of enteral nutrition (EN) in treating active Crohn’s disease in children.

Methods

MEDLINE, EMBASE and The Cochrane Library (up to February 2007) were searched for randomized controlled trials (RCTs) relevant to Crohn’s disease and EN in children.

Results

We included 11 RCTs (n = 394). Seven RCTs (n = 204) compared EN with corticosteroid therapy. On the basis of pooled results of four RCTs (n = 144), we found no significant difference in the remission rates between groups (relative risk, RR 0.97, 95% CI 0.7–1.4, random effect model). Four RCTs (n = 190) compared two EN regimens. One of the four RCTs (n = 50) revealed a significant increase in the percentage of patients achieving remission in the total EN group compared with the partial EN group (RR 2.7, 95% CI 1–7.4). Because of lack of data, formal pooling of results was not possible for many outcomes (e.g., time until remission, duration of remission, growth data).

Conclusions

Limited data suggest similar efficacy for EN and corticosteroids. As the number of patients needed to provide a definite answer is too large, future studies should focus on detailed outcome measurements including growth and quality of life.
Antibodies to SS‐A/Ro‐52kD and centromere in autoimmune liver disease: a clue to diagnosis and prognosis of primary biliary cirrhosis
Authors: GRANITO A. , MURATORI P. , MURATORI L. , PAPPAS G. , CASSANI F. , WORTHINGTON J. , FERRI S. , QUARNETI C. , CIPRIANO V. , DE MOLO C. , LENZI M. , CHAPMAN R. W. , BIANCHI F. B.
Published: July 2010

Background Primary biliary cirrhosis (PBC) may be associated with various rheumatological disorders.

Aim

To investigate the frequency and significance of ‘rheumatological’ antinuclear antibodies in the field of autoimmune chronic liver disease, with special regard to PBC.

Methods

We studied 105 patients with PBC, 162 autoimmune liver disease controls (type 1 and 2 autoimmune hepatitis, primary sclerosing cholangitis), 30 systemic lupus erythematosus and 50 blood donors. Sera were tested for the presence of antibodies to extractable nuclear antigens (anti‐ENA) by counterimmunoelectrophoresis, enzyme‐linked and immunoblot (IB) assay, and for the presence of anti‐centromere antibodies (ACA) by indirect immunofluorescence on HEp‐2 cells and IB.

Results

The overall prevalence of IB‐detected anti‐ENA in PBC (30%) was higher than in type 1 autoimmune hepatitis (2.5%, P < 0.0001), type 2 autoimmune hepatitis (0%, P < 0.0001) and primary sclerosing cholangitis (11.5%, P = 0.006) and lower than in systemic lupus erythematosus (53%, P = 0.03). The most frequent anti‐ENA reactivity in PBC was anti‐SSA/Ro‐52kD (28%). ACA were detected by IB in 21% PBC patients and never in the other subjects (P < 0.0001). Anti‐SS‐A/Ro/52kD positive PBC patients had at the time of diagnosis a more advanced histological stage (P = 0.01) and higher serum levels of bilirubin (P = 0.01) and IgM (P = 0.03) compared with negative ones.

Conclusions

In the autoimmune liver disease setting, anti‐SS‐A/Ro‐52kD and ACA have a high specificity for PBC and can thus be of diagnostic relevance in anti‐mitochondrial antibodies negative cases. If confirmed in further studies with adequate follow‐up, anti‐SS‐A/Ro‐52kD antibodies might identify PBC patients with a more advanced and active disease.
Long‐acting octreotide as rescue therapy in chronic bleeding from gastrointestinal angiodysplasia
Authors: SCAGLIONE G. , PIETRINI L. , RUSSO F. , FRANCO M. R. , SORRENTINI I.
Published: July 2010

Background

Octreotide has shown to be effective against rebleeding from gastrointestinal angiodysplasias, but a long‐term daily parenteral administration is recommended. Long‐acting octreotide (LAR‐OCT) could overcome such a limitation, but it has not been studied extensively.

Aim

To investigate the usefulness of long‐acting octreotide in the control of chronic bleeding from gastrointestinal angiodysplasias.

Methods

Thirteen patients with chronic gastrointestinal bleeding because of angiodysplasias were enrolled. Diagnosis was made by endoscopy and wireless video capsule. Long‐acting octreotide was administered intramuscularly at a dosage of 10 mg/monthly for 1 year. Patients were followed up for a minimum period of 1 year, and haemoglobin levels, blood transfusions, iron supplementation and hospitalizations were recorded 1 year before and after starting long‐acting octreotide therapy.

Results

Follow‐up ranged from 12 to 60 months. Nine of 13 patients (69%) did not need blood transfusions and iron supplementation any longer; a partial improvement was observed in one patient; no effect was found in the others. No side effect was recorded in any patient.

Conclusions

Long‐acting octreotide for 1 year may be beneficial as a rescue therapy for controlling chronic bleeding from gastrointestinal angiodysplasias in patients not eligible for surgery. Its monthly administration represents an advantage, which makes such a formulation the choice when a long‐term treatment is mandatory.
Review article: renal function assessment in cirrhosis – difficulties and alternative measurements
Authors: CHOLONGITAS E. , SHUSANG V. , MARELLI L. , NAIR D. , THOMAS M. , PATCH D. , BURNS A. , SWENY P. , BURROUGHS A. K.
Published: July 2010

Background  Renal function in patients with cirrhosis is important prognostically, both before and following liver transplantation. Its prognostic impact is reflected by the inclusion of serum creatinine in the model for end‐stage liver disease score, which is now used for recipient prioritization on liver transplantation waiting lists in the USA.

Aim  To review the accuracy of the surrogate markers for the assessment of renal function, i.e. glomerular filtration rate, particularly in patients with cirrhosis.

Method  We reviewed the available literature in PubMed regarding the markers for GFR evaluation and the factors which affect their accuracy in cirrhosis.

Results  Although creatinine is widely available, it is an unreliable marker of glomerular filtration rate, particularly in patients with cirrhosis. Clearance of exogenous markers is considered the ‘gold standard’, but this methodology has many drawbacks, particularly poor applicability. Several mathematical formulae for estimated glomerular filtration rate are used to overcome some of these limitations: Cockcroft‐Gault and Modification of Diet in Renal Disease formulae are the most frequently applied, but they are based on serum creatinine.

Conclusions  Due to the inaccuracy of serum creatinine and its derived formulae in estimating glomerular filtration rate, alternative serum markers, such as cystatin C, and new formulae are desirable. These need formal evaluation in patients with cirrhosis so as to have a reliable surrogate of glomerular filtration rate, and to obviate many problems that are associated with using creatinine and estimated glomerular filtration rate.
Systematic review: racecadotril in the treatment of acute diarrhoea in children
Authors: SZAJEWSKA H. , RUSZCZYŃSKI M. , CHMIELEWSKA A. , WIECZOREK J.
Published: July 2010

Background

Racecadotril (acetorphan) is an antisecretory drug that exerts its antidiarrhoeal effects by inhibiting intestinal enkephalinase.

Aim

To summarize studies testing the efficacy and safety of racecadotril for treating children with acute gastroenteritis.

Methods

Reports were gathered by searching electronic databases MEDLINE, EMBASE, the Cochrane Library (all up to April 2007), relevant journals, and bibliographies of reviewed articles. Only randomized‐controlled trials were included.

Results

Three randomized‐controlled trials (471 participants) met the inclusion criteria. Two trials reported stool output, and data suggested less stool output in the racecadotril group than in the control group. The duration of diarrhoea was significantly reduced in the three trials reporting this outcome. Achievement of a cure by day 5 was similar in both groups. Adverse effects were similar in both groups.

Conclusions

The small number of included trials provided some evidence in favour of the use of racecadotril over placebo or no intervention, to reduce the stool output and duration of diarrhoea in children with acute gastroenteritis. However, more data in out‐patients are needed. The safety as well as the cost‐effectiveness of the therapy should be explored, before routine therapy with racecadotril is recommended.
Differences in the management of Crohn’s disease among experts and community providers, based on a national survey of sample case vignettes
Authors: ESRAILIAN E. , SPIEGEL B. M. R. , TARGOWNIK L. E. , DUBINSKY M. C. , TARGAN S. R. , GRALNEK I. M.
Published: July 2010

Background  When faced with the same set of facts, healthcare providers often make different diagnoses, employ different tests and prescribe disparate therapies.

Aim  To perform a national survey to measure process of care and variations in decision‐making in Crohn’s disease, and the compared results between experts and community providers.

Methods  We constructed a survey with five vignettes to elicit provider beliefs regarding the appropriateness of diagnostic tests and therapies in Crohn’s disease. We measured agreement between community gastroenterologists and Crohn’s disease experts, and measured variation within each group using the RAND Disagreement Index (DI), which is a validated measure of provider variation.

Results  We received 186 responses (42% response rate). Experts and community providers generally agreed on diagnostic testing decisions in Crohn’s disease. However, there was a significant disagreement between groups for several decisions (use of 5‐aminosalicylate in particular), and there was evidence of ‘extreme variation’ (defined as DI > 1.0) within groups across a range of decisions.

Conclusions  Although experts and community providers are in general consensus about diagnostic decision‐making in Crohn’s disease, extreme variation exists both between and within groups for key therapeutic decisions in Crohn’s disease. We must understand and decrease this variation prior to future efforts of creating explicit quality indicators in Crohn’s disease.
Association between reflux oesophagitis and features of the metabolic syndrome in Japan
Authors: MOKI F. , KUSANO M. , MIZUIDE M. , SHIMOYAMA Y. , KAWAMURA O. , TAKAGI H. , IMAI T. , MORI M.
Published: July 2010

Background  There have been many reports about the relationship between reflux oesophagitis and obesity, but not the metabolic syndrome.

Aim  To review upper gastrointestinal endoscopic findings and screening data obtained in healthy subjects, and assess relations between reflux oesophagitis and features of the metabolic syndrome.

Methods  In 3599 men and 1560 women, the prevalence of reflux oesophagitis was assessed in relation to the age, body mass index, blood pressure, triglycerides and fasting blood glucose. Logistic regression analysis was used to calculate odds ratio for risk factors.

Results  The overall prevalence of reflux oesophagitis was 4%, and it increased with age in women. Prevalence of reflux oesophagitis increased significantly with an increase of body mass index, blood pressure, triglycerides and fasting blood glucose. On multivariate analysis, male sex (odds ratio: 2.5; 95% confidence interval: 1.6–3.8), obesity (1.9; 1.4–2.5), hyperglycaemia (1.7; 1.2–2.4) and hypertension (1.5; 1.1–2.1) were independent risk factors for reflux oesophagitis. Among both men and women, those with reflux oesophagitis were significantly more likely to have two or more of these risk factors than non‐reflux oesophagitis subjects.

Conclusions  Components of the metabolic syndrome are associated with the occurrence of reflux oesophagitis. Therefore, some risk factors may be common to reflux oesophagitis and the metabolic syndrome.
Medical management of mild to moderate Crohn’s disease: evidence‐based treatment algorithms for induction and maintenance of remission
Authors: SANDBORN W. J. , FEAGAN B. G. , LICHTENSTEIN G. R.
Published: July 2010

Background Patients with Crohn’s disease alternate between periods of active, symptomatic disease and periods of remission. The treatment goal for Crohn’s disease is to induce and then maintain remission of symptoms.

Aim To review evidence from randomized, controlled, clinical trials on medical therapies for inducing and maintaining remission in patients with mild‐to‐moderate Crohn’s disease, and to suggest the best evidence‐based approaches for induction and maintenance therapies.

Methods PubMed search using the following terms: sulfasalazine or salicylazosulfapyridine or aminosalicylate or aminosalicylic acid or mesalamine or mesalazine or corticosteroid or prednisone or prednisolone or methylprednisolone or budesonide or antibiotic or metronidazole or ciprofloxacin or immunosuppressive or azathioprine or mercaptopurine or thiopurine or methotrexate and Crohn’s disease.

Results Randomized, controlled trials demonstrated that sulfasalazine, budesonide, and conventional corticosteroids are effective for inducing remission of mild‐to‐moderate Crohn’s disease when administered for a period of 8–16 weeks. An ideal maintenance therapy does not currently exist.

Conclusions Selection of maintenance therapy is based on a combination of evidence from controlled trials and patient features including disease severity and location, co‐morbidities, previous response to treatment, and previous surgical resection. The options for maintenance therapy include therapy cessation and patient observation following successful induction, budesonide, or immunosuppressive therapy.
Clinical trial: effect of mitemcinal (a motilin agonist) on gastric emptying in patients with gastroparesis – a randomized, multicentre, placebo‐controlled study
Authors: MCCALLUM R. W. , CYNSHI O. ,   INVESTIGATIVE TEAM
Published: July 2010

Background  Mitemcinal is an orally active motilin agonist that could potentially improve gastric emptying.

Aim  To investigate the effect of mitemcinal on gastric emptying in patients with idiopathic and diabetic gastroparesis.

Methods  In a randomized, double‐blind design, 106 patients were randomized into four dosing regimens (22 to placebo and 21 each to mitemcinal 10 mg, 20 mg, 30 mg bid or 20 mg tid) for 28 days. A standardized scintigraphic gastric emptying test was performed at screening and again after completing the 4‐week protocol.

Results  All doses of mitemcinal showed prokinetic activity. A significant improvement in meal retention at 240 min was noted even in the lowest dose group with the greatest improvement observed with 30 mg bid group (75% vs. 10% in placebo group). Diabetic patients responded better than the idiopathic subgroup. In diabetic patients, blood glucose at 1 h after a meal showed dose‐dependent elevation. Although gastroparetic symptoms improved with both mitemcinal and placebo, the prominent placebo effect was not statistically exceeded by mitemcinal. Baseline scintigraphy results exhibited no clear correlation between the severity of gastroparetic symptoms and the status of gastric emptying.

Conclusion  Mitemcinal is capable of accelerating gastric emptying in both diabetic and idiopathic patients with gastroparesis.
Clinical trial: modulation of human placental multidrug resistance proteins in cholestasis of pregnancy by ursodeoxycholic acid
Authors: AZZAROLI F. , MENNONE A. , FELETTI V. , SIMONI P. , BAGLIVO E. , MONTAGNANI M. , RIZZO N. , PELUSI G. , DE ALOYSIO D. , LODATO F. , FESTI D. , COLECCHIA A. , RODA E. , BOYER J. L. , MAZZELLA G.
Published: July 2010

Background  The effects of ursodeoxycholic acid on human placental bile acids and bilirubin transporters in intrahepatic cholestasis of pregnancy are still undefined.

Aim  To evaluate whether ursodeoxycholic acid affects MRP2, MRP3 and MRP4 expression in the placenta.

Materials and methods  Forty‐three pregnant women were enrolled; fourteen subjects had physiological pregnancies. Intrahepatic cholestasis of pregnancy patients were divided into two groups: (i) 13 received ursodeoxycholic acid (20 mg/kg/day) and (ii) 16 untreated. Total bile acid and bilirubin in serum and cord blood were determined in each subject. Multidrug resistance proteins expression (immunoblot, quantitative real‐time PCR) was evaluated in placentas collected at delivery. anova test was used for statistical analysis of data.

Results  Ursodeoxycholic acid administration significantly improved maternal serum bile acid and cord blood bilirubin and bile acid levels. MRP2 protein and RNA expression was significantly increased in placentas from treated patients compared to controls (P < 0.001 and P < 0.01, respectively). MRP3 protein expression was not significantly different between the groups while RNA expression was significantly decreased in treated patients (P < 0.01). MRP4 did not show significant differences between the groups.

Conclusions  Ursodeoxycholic acid administration induces placental MRP2 expression, and reduces bilirubin and bile acid levels in cord blood.
Clinical trial: a randomized‐controlled crossover study of intrapyloric injection of botulinum toxin in gastroparesis
Authors: ARTS J. , HOLVOET L. , CAENEPEEL P. , BISSCHOPS R. , SIFRIM D. , VERBEKE K. , JANSSENS J. , TACK J.
Published: July 2010

Background  Uncontrolled studies suggest benefit of intrapyloric injection of botulinum toxin (botox) for the treatment of gastroparesis, but controlled data are lacking.

Aim  To perform a controlled study of botox injection in gastroparesis.

Methods  Twenty‐three gastroparesis patients (five men, age 45 ± 3, 19 idiopathic) underwent two upper endoscopies with 4‐week interval, with injection of saline or botox 4 × 25 U in a randomized double‐blind‐controlled crossover fashion. Before the start of the study and 4 weeks after each treatment, they underwent a solid and liquid gastric emptying breath test with measurement of meal‐related symptom scores, and filled out the Gastroparesis Cardinal Symptom Index. Results (mean S.E.M.) were compared using Student’s t‐test.

Results  Twelve patients received botox and 11 saline as the first injection. Significant improvement in emptying and Gastroparesis Cardinal Symptom Index was seen after initial injection of saline or botox. No further improvement occurred after the second injection (respectively, botox and saline). Pooled data for both treatment groups showed no significant difference in improvements of solid t1/2 (3.4 ± 7.4 vs. 16.3 ± 8.3, N.S.) and liquid t1/2 (8.2 ± 13.7 vs. 22.5 ± 7.7, N.S.), meal‐related symptom scores or Gastroparesis Cardinal Symptoms Index (GCSI; 6.1 ± 1.5 vs. 3.8 ± 1.5, N.S.).

Conclusion  In a cohort of predominantly idiopathic gastroparesis patients, botox is not superior to placebo in improving either symptoms or the rate of gastric emptying.
Clinical trial: randomized‐controlled clinical study comparing the efficacy and safety of a low‐volume vs. a high‐volume mesalazine foam in active distal ulcerative colitis
Authors: ELIAKIM R. , TULASSAY Z. , KUPCINSKAS L. , ADAMONIS K. , POKROTNIEKS J. , BAR‐MEIR S. , LAVY A. , MUELLER R. , GREINWALD R. , CHERMESH I. , GROSS V. ,   ON BEHALF OF THE INTERNATIONAL SALOFALK FOAM STUDY GROUP
Published: July 2010

Background  Rectally administered mesalazine (mesalamine; 5‐aminosalicylic acid) is the first‐line therapy for treatment of distal ulcerative colitis. Recently, a high‐volume 5‐aminosalicylic acid foam has been shown to be as effective and safe as standard 5‐aminosalicylic acid enema.

Aim  To study the efficacy and safety of a low‐volume vs. a high‐volume 5‐aminosalicylic acid foam.

Methods  In this investigator‐blinded study, patients with active distal ulcerative colitis [Clinical Activity Index (CAI) > 4, Endoscopic Index ≥ 4] were randomized to receive 2 × 1 g/30 mL low‐volume (n = 163) or 2 × 1 g/60 mL high‐volume 5‐aminosalicylic acid foam (n = 167) for 42 days. Primary end point was clinical remission (CAI ≤ 4) at the final/withdrawal visit (per‐protocol).

Results  330 patients were evaluable for efficacy and safety by intention‐to‐treat, 290 for per‐protocol analysis. Clinical remission rates at week 6 (per‐protocol) were 77% on low‐volume foam vs. 77% on high‐volume foam (P = 0.00002 for non‐inferiority). The low‐volume foam was associated with a lower frequency of severe discomfort, pain and retention problems.

Conclusions  Low‐volume 5‐aminosalicylic acid foam is as effective and safe as a high‐volume 5‐aminosalicylic acid foam in the treatment of active distal ulcerative colitis, but offers compliance advantages compared to the high‐volume preparation.
Clinical trial: the effects of adding ranitidine at night to twice daily omeprazole therapy on nocturnal acid breakthrough and acid reflux in patients with systemic sclerosis – a randomized controlled, cross‐over trial
Authors: JANIAK P. , THUMSHIRN M. , MENNE D. , FOX M. , HALIM S. , FRIED M. , BRÜHLMANN P. , DISTLER O. , SCHWIZER W.
Published: July 2010

Background  Gastro‐oesophageal reflux disease (GERD) is an important problem in systemic sclerosis due to impaired salivation and oesophageal function.

Aim  To determine the efficacy of adding ranitidine at bedtime to control nocturnal acid breakthrough (NAB) and GERD in patients with systemic sclerosis already prescribed high‐dose omeprazole.

Methods  Patients with systemic sclerosis and GERD symptoms (n = 14) were treated with omeprazole 20 mg b.d. and either placebo or ranitidine 300 mg at bedtime for 6 weeks in a randomized, cross‐over, placebo controlled study. At the end of each period a 24 h pH‐study with intragastric and oesophageal pH measurement was performed.

Results  Pathological acid reflux occurred in eight patients with omeprazole/placebo and in seven with omeprazole/ranitidine (P = ns) with technically adequate oesophageal pH‐studies (n = 13). NAB was present in eight patients with omeprazole/placebo and six with omeprazole/ranitidine (P = ns) in whom technically adequate gastric pH‐studies were obtained (n = 10). The addition of ranitidine had no consistent effect on patient symptoms or quality of life.

Conclusion  Many patients with systemic sclerosis experienced NAB and pathological oesophageal acid exposure despite high‐dose acid suppression with omeprazole b.d. Adding ranitidine at bedtime did not improve NAB, GERD or quality of life in this population.
Clinical trial: pharmacodynamics and pharmacokinetics of re‐treatment with fixed‐dose induction of peginterferon α‐2a in hepatitis C virus genotype 1 true non‐responder patients
Authors: DIAGO M. , CRESPO J. , OLVEIRA A. , PÉREZ R. , BÁRCENA R. , SÁNCHEZ‐TAPIAS J. M. , MUÑOZ‐SÁNCHEZ M. , ROMERO‐GÓMEZ M.
Published: July 2010

Background  Patients infected with hepatitis C virus genotype 1 who are true non‐responders to previous therapy suffer from a very difficult‐to‐cure disease. New approaches to treatment are necessary.

Aim  To explore the efficacy, pharmacokinetics and safety of fixed‐dose induction with peginterferon α‐2a and ribavirin in this difficult‐to‐cure population.

Methods  Seventy‐five hepatitis C virus genotype 1 true non‐responder patients to a previous interferon‐based combination regimen were randomised to receive peginterferon α‐2a 360, 270 or 180 μg/week for 12 weeks, followed by 180 μg/week for 36 weeks, in combination with ribavirin (1000/1200 mg/day). Peginterferon α‐2a concentration was measured throughout the study.

Results  Sustained virological response rates were 38%, 30% and 18%, in the 360, 270 and 180 μg/week groups, respectively (relapse rates: 25%, 50% and 64%, respectively). The area under the serum concentration‐time curve of peginterferon α‐2a from 0–12 weeks increased in a dose‐dependent manner (P < 0.0001) and was associated with the sustained virological response (odds ratio: 1.35; 95% CI: 0.89, 2.06). The three regimens were equally well tolerated.

Conclusion  Fixed‐dose induction of peginterferon α‐2a resulted in increased drug exposure and improved the likelihood of achieving a cure, without compromising safety in hepatitis C virus genotype 1 true non‐responder patients.
Review article: the laryngological manifestations of reflux disease; why the scepticism?
Authors: MAHIEU H. F.
Published: July 2010

Background  Despite increasing clinical and experimental evidence of its existence, otolaryngological manifestations of reflux disease remain controversial, concerning diagnosis as well as treatment.

Aim  Proper understanding of laryngopharyngeal reflux disease (LPRD).

Method  Review of literature.

Results  Scepticism concerning LPRD is based upon differences between gastro‐oesophageal reflux disease and LPRD; lack of specificity and sensitivity of diagnostic tests to confirm LPRD; non‐specificity of laryngological symptoms, which are difficult to distinguish from other causes of upper respiratory tract inflammation; non‐specificity of laryngological signs in laryngoscopy, with high intra‐ and inter‐observer variability in evaluation; diagnosis of LPRD is essentially only based on a combination of diagnostic signs and symptoms, which cannot be attributed to other pathology; slow, or sometimes lack of, response of LPRD symptoms to proton pump inhibitor (PPI) medication and lack of evidence concerning efficacy of PPIs in placebo‐controlled trials.

Conclusions  LPRD remains a diagnosis by exclusion and resolution of symptoms following 4‐month trial of 40 mg PPI twice daily is, for all practical purposes, considered proof of the initial diagnosis. However, non‐response does not exclude LPRD as PPIs have no influence on noxious non‐acid components of the refluxate.
Review article: inflammatory bowel disease and genetics
Authors: WEERSMA R. K. , VAN DULLEMEN H. M. , VAN DER STEEGE G. , NOLTE I. M. , KLEIBEUKER J. H. , DIJKSTRA G.
Published: July 2010

Introduction  Inflammatory bowel disease (IBD) comprising ulcerative colitis (UC) and Crohn's disease (CD) is multigenic disorder. Tremendous progress has been achieved in unravelling the genetic background of IBD. It has led to the discovery of mutations in NOD2 associated with ileal CD and numerous other genes have been found to be associated with IBD susceptibility.

Methods  A review of the literature on the genetic background of IBD was performed.

Results  It is only partially understood how mutations in NOD2 lead to CD. Mouse models, in vitro data and studies in humans offer conflicting data as regards whether there is a loss or gain of function of NOD2 in CD. Several additional genes have been identified of which only a few are currently being recognized as potential disease causing or disease modifying genes. Promising candidate genes include TLR4, MDR1, NOD1 (CARD4), DLG5 as well as the IBD5 locus including SLC22A4/5.

Conclusions  Although genetic research has not yet led to a better prediction of the disease course or patient selection for medical therapy, remarkable progress has been made in the understanding of the pathogenesis of IBD. For future genetic research, accurate phenotyping of patients is very important and large population‐based cohorts are needed. Eventually, genetic research may be able to classify different disease phenotypes on a more detailed molecular basis and may provide important contributions in the development of new therapeutic approaches.
Review article: stem cell transplantation for the treatment of gastrointestinal diseases – current applications and future perspectives
Authors: AL‐TOMA A. , MULDER C. J. J.
Published: July 2010

Background  Haematopoietic stem cell transplantation (HSCT) can be used to cure or ameliorate a variety of non‐malignant diseases. These range from inherent defects of haematopoiesis, through metabolic diseases, to severe autoimmune diseases. The rationale for this strategy is based on the concept of immunoablation using high‐dose chemotherapy, with subsequent regeneration of naïve T‐lymphocytes derived from reinfused haematopoietic progenitor cells. Possibly the use of SCT allows the administration of high‐dose chemotherapy resulting in a prompt remission in these therapy‐refractory patients.

Aim  This review highlights the major scientific developments and defines the areas of successful use of HSCT in gastrointestinal disorders and gives a perspective on possible future applications.

Methods  A search in the Medline has been conducted and all relevant published data were analysed.

Results  HSCT has been proved successful in treating refractory Crohn’s disease. A selected group of refractory coeliac patients having a high risk of developing enteropathy associated T‐cell lymphoma has been recently treated with promising results. In cryptogenic cirrhosis, basic research and unpublished data concerning mesenchymal SCT are encouraging.

Conclusion  In refractory autoimmune gastrointestinal diseases, it seems that high‐dose chemotherapy followed by HSCT is feasible and safe and might result in long‐term improvement of disease activity.
Review article: success and failure of nucleoside and nucleotide analogues in chronic hepatitis B
Authors: LEEMANS W. F. , TER BORG M. J. , DE MAN R. A.
Published: July 2010

Background  Strong suppression of viral replication and normalization of alanine aminotransferase is feasible with nucleos(t)ide analogues. It is estimated viral replication and liver inflammation can be controlled in 90% of patients with chronic hepatitis B with the current available treatments.

Aim  To review the studies currently available on the management of chronic hepatitis B with nucleos(t)ide analogues.

Results  Although very potent, nucleos(t)ide analogues are not effective in every patient. Some factors are known to influence treatment outcome, but many host and viral factors are still unknown. Stopping rules have to be defined to assess treatment efficacy in an early stage and change the regimen. Discontinuation of nucleos(t)ide analogues is often followed by reactivation of HBV. Data on the risk factors for relapse are necessary in order to decide if treatment can be safely discontinued. Another major drawback of nucleos(t)ide analogues is the emergence of resistance. The efficacy of compounds for the treatment of mutant virus and the impact of cross‐resistance is largely unknown. The use of combination therapy to prevent resistance looks promising, but has to be proven.

Conclusions  HBV has become a treatable disease, however much research is needed to optimize treatment for individual patients and treatment failures.
Review article: non‐alcoholic fatty liver disease in morbidly obese patients and the effect of bariatric surgery
Authors: DE RIDDER R. J. J. , SCHOON E. J. , SMULDERS J. F. , VAN HOUT G. C. M. , STOCKBRÜGGER R. W. , KOEK G. H.
Published: July 2010

Background  Morbid obesity is strongly associated with non‐alcoholic fatty liver disease. The effects of bariatric surgery on liver tests an histolological abnormalities after weight loss are controversial.

Aim  To review the literature on the prevalence of non‐alcoholic fatty liver disease in patients with morbid obesity with respect to laboratory and histopathological parameters and the effect of weight loss on these parameters after bariatric surgery.

Results  Standard liver tests do not seem to be a sensitive tool for the assessment and follow‐up of non‐alcoholic fatty liver disease in obesity. In nearly all patients with morbid obesity, histological abnormalities reflecting non‐alcoholic fatty liver disease are present. Bariatric surgery in these patients will decrease the grade of steatosis. However, there are some concerns about the effect of bariatric surgery on hepatic inflammation and fibrosis. In particular, older follow‐up studies reported negative results as opposed to more recent studies, which also showed improvement in hepatic inflammation and fibrosis. Unfortunately, most studies had limitations because of the selection of patients.

Conclusion  Despite limitations in many studies, bariatric surgery seems to be a promising treatment in patients with obesity presenting with non‐alcoholic fatty liver disease.