Abstracts to Falk Gastro-Info 6/2020
Am J Gastroenterol. 2020;115(5):766–73
Pan L, Mu M, Yang P, Sun Y, Wang R, Yan J, Li P, Hu B, Wang J, Hu C, Jin Y, Niu X, Ping R, Du Y, Li T, Xu G, Hu Q, Tu L
Clinical characteristics of COVID-19 patients with digestive symptoms in Hubei, China: A descriptive, cross-sectional, multicenter study
Objective: Since the outbreak of Coronavirus Disease 2019 (COVID-19) in December 2019, various digestive symptoms have been frequently reported in patients infected with the virus. In this study, the authors aimed to further investigate the prevalence and outcomes of COVID-19 patients with digestive symptoms.
Methods: In this descriptive, cross-sectional, multicenter study, they enrolled confirmed patients with COVID-19 who presented to 3 hospitals from January 18, 2020, to February 28, 2020. All patients were confirmed by real-time polymerase chain reaction and were analyzed for clinical characteristics, laboratory data, and treatment. Data were followed up until March 18, 2020.
Results: In the present study, 204 patients with COVID-19 and full laboratory, imaging, and historical data were analyzed. The average age was 52.9 years (SD ± 16), including 107 men and 97 women. Although most patients presented to the hospital with fever or respiratory symptoms, 103 patients (50.5%) were found which reported a digestive symptom, including lack of appetite (81 cases [78.6%]), diarrhea (35 cases [34%]), vomiting (4 cases [3.9%]), and abdominal pain (2 cases [1.9%]). If lack of appetite is excluded from the analysis (because it is less specific for the gastrointestinal tract), there were 38 total cases (18.6%) where patients presented with a gastrointestinal-specific symptom, including diarrhea, vomiting, or abdominal pain. Patients with digestive symptoms had a significantly longer time from onset to admission than patients without digestive symptoms (9.0 days vs. 7.3 days). In 6 cases, there were digestive symptoms, but no respiratory symptoms. As the severity of the disease increased, digestive symptoms became more pronounced. Patients with digestive symptoms had higher mean liver enzyme levels, lower monocyte count, longer prothrombin time, and received more antimicrobial treatment than those without digestive symptoms.
Discussion: Digestive symptoms are common in patients with COVID-19. Moreover, these patients have a longer time from onset to admission, evidence of longer coagulation, and higher liver enzyme levels. Clinicians should recognize that digestive symptoms, such as diarrhea, are commonly among the presenting features of COVID-19 and that the index of suspicion may need to be raised earlier in at-risk patients presenting with digestive symptoms. However, further large sample studies are needed to confirm these findings.
Prof. Dr. L. Tu, Department of Critical Care Medicine, Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China, E-Mail: email@example.com
Prof. Dr. Q. Hu, Cancer Center, Renmin Hospital of Wuhan University, Wuhan, China, E-Mail: firstname.lastname@example.org
Prof. Dr. G. Xu, The Second Medical Center and National Clinical Research Center for Geriatric Diseases, Chinese PLA General Hospital, Beijing, China, E-Mail: email@example.com
El-Salhy M, Hatlebakk JG, Gilja OH, Bråthen Kristoffersen A, Hausken T
Efficacy of fecal microbiota transplantation for patients with irritable bowel syndrome in a randomized, double-blind, placebo-controlled study
Objective: Fecal microbiota transplantation (FMT) from healthy donors to patients with irritable bowel syndrome (IBS) has been attempted in 2 previous double-blind, placebo-controlled studies. While one of those studies found improvement of the IBS symptoms, the other found no effect. The present study was conducted to clarify these contradictory findings.
Design: This randomized, double-blind, placebo-controlled study randomized 165 patients with IBS to placebo (own feces), 30 g FMT or 60 g FMT at a ratio of 1:1:1. The material for FMT was obtained from 1 healthy, well-characterized donor, frozen and administered via gastroscope. The primary outcome was a reduction in the IBS symptoms at 3 months after FMT (response). A response was defined as a decrease of 50 or more points in the total IBS symptom score. The secondary outcome was a reduction in the dysbiosis index (DI) and a change in the intestinal bacterial profile, analyzed by 16S rRNA gene sequencing, at 1 month following FMT.
Results: Responses occurred in 23.6%, 76.9% (p < 0.0001) and 89.1% (p < 0.0001) of the patients who received placebo, 30 g FMT and 60 g FMT, respectively. These were accompanied by significant improvements in fatigue and the quality of life in patients who received FMT. The intestinal bacterial profiles changed also significantly in the groups received FMT. The FMT adverse events were mild self-limiting gastrointestinal symptoms.
Conclusions: Fecal microbiota transplantation (FMT) is an effective treatment for patients with irritable bowel syndrome. Utilizing a well-defined donor with a normal dysbiosis index and favorable specific microbial signature is essential for successful FMT.
Prof. Dr. M. El-Salhy, Section of Gastroenterology, Department of Medicine, Stord Hospital, Tysevegen 64, 5416 Stord, Norway, E-Mail: firstname.lastname@example.org
Panaccione R, Colombel JF, Travis SPL, Bossuyt P, Baert F, Vaňásek T, Danalioğlu A, Novacek G, Armuzzi A, Reinisch W, Johnson S, Buessing M, Neimark E, Petersson J, Lee WJ, D'Haens GR
Tight control for Crohn's disease with adalimumab-based treatment is cost-effective: An economic assessment of the CALM trial
Objective: To evaluate the cost-effectiveness of an inflammatory biomarker and clinical symptom directed tight control strategy (TC) compared with symptom-based clinical management (CM) in patients with Crohn's disease (CD) naive to immunosuppressants and biologics using a UK public payer perspective.
Design: A regression model estimated weekly CD Activity Index (CDAI)-based transition matrices (remission: CDAI < 150, moderate: CDAI ≥ 150 to < 300, severe: CDAI ≥ 300 to < 450, very severe: CDAI ≥ 450) based on the Effect of Tight Control Management on Crohn's Disease (CALM) trial. A regression predicted hospitalizations. Health utilities and costs were applied to health states. Work productivity was monetized and included in sensitivity analyses. Remission rate, CD-related hospitalizations, adalimumab injections, other direct medical costs, quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratio (ICER) were calculated.
Results: Over 48 weeks, TC was associated with a higher clinical remission (CDAI < 150) rate (58.2% vs. 46.8%), fewer CD-related hospitalizations (0.124 vs. 0.297 events per patient) and more injections of adalimumab (40 mg s.c.) (mean 31.0 vs. 24.7) than CM. TC was associated with 0.032 higher QALYs and ₤593 higher total medical costs. The ICER was ₤18 656 per QALY. The ICER was cost-effective in 57.9% of simulations. TC became dominant, meaning less costly but more effective, when work productivity was included.
Conclusion: A tight control (TC) strategy as used in the CALM trial is cost-effective compared with clinical management. Incorporating costs related to work productivity increases the economic value of TC. Cross-national inferences from this analysis should be made with caution given differences in healthcare systems.
Prof. Dr. R. Panaccione, Inflammatory Bowel Disease Unit, Division of Gastroenterology and Hepatology, Department of Medicine, University of Calgary, 6D32 TRW Building, 3280 Hospital Drive, Calgary, AB T2N 4N1, Canada, E-Mail: email@example.com
Taylor RS, Taylor RJ, Bayliss S, Hagström H, Nasr P, Schattenberg JM, Ishigami M, Toyoda H, Wong VWS, Peleg N, Shlomai A, Sebastiani G, Seko Y, Bhala N, Younossi ZM, Anstee QM, McPherson S, Newsome PN
Association between fibrosis stage and outcomes of patients with non-alcoholic fatty liver disease: A systematic review and meta-analysis
Background and aims: Biopsy-confirmed liver fibrosis is a prognostic factor for patients with non-alcoholic fatty liver disease (NAFLD). A systematic review was performed to quantify the prognostic value of fibrosis stage in patients with NAFLD and the subgroup of patients with non-alcoholic steatohepatitis (NASH) and to assess the evidence that change in fibrosis stage is a surrogate end point.
Methods: The authors searched the Medline, Embase, Cochrane Library, and trial registry databases through August 2018 for prospective or retrospective cohort studies of liver-related clinical events and outcomes in adults with NAFLD or NASH. They collected data on mortality (all cause- and liver-related) and morbidity (cirrhosis, liver cancer, and all liver-related events) by stage of fibrosis, determined by biopsy, for patients with NAFLD or NASH. Using fibrosis stage 0 as a reference population, they calculated fibrosis stage-specific relative risk (RR) and 95% confidence interval (CI) values for mortality and morbidities. Fixed-effect and random-effect model meta-analyses were performed. Meta-regression was used to examine associations among study design (prospective vs retrospective cohort), overall risk of bias (medium or high), and mean duration of follow-up (in years).
Results: This meta-analysis included 13 studies, comprising 4428 patients with NAFLD; 2875 of these were reported to have NASH. Compared with no fibrosis (stage 0), unadjusted risk increased with increasing stage of fibrosis (stage 0 vs. 4): all-cause mortality RR = 3.42 (95% CI: 2.63–4.46); liver-related mortality RR = 11.13 (95% CI: 4.15–29.84); liver transplantion RR = 5.42 (95% CI: 1.05–27.89); and liver-related events RR = 12.78 (95% CI: 6.85–23.85). The magnitude of RR did not differ significantly after adjustment for confounders, including age or sex in the subgroup of NAFLD patients with NASH. Three studies examined the effects of increasing fibrosis on quality of life had inconsistent findings.
Conclusions: In a systematic review and meta-analysis, biopsy-confirmed fibrosis was found to be associated with risk of mortality and liver-related morbidity in patients with non-alcoholic fatty liver disease, with and without adjustment for confounding factors and in patients with reported non-alcoholic steatohepatitis. Further studies are needed to assess the association between fibrosis stage and patient quality of life and establish that change in liver fibrosis stage is a valid end point for use in clinical trials.
Prof. Dr. R.S. Taylor, MRC/CSO Social and Public Health Sciences Unit, University of Glasgow, Top Floor, 200 Renfield Street, Glasgow, G2 3AX, UK, E-Mail: firstname.lastname@example.org
Gouya L, Ventura P, Balwani M, Bissell DM, Rees DC, Stölzel U, Phillips JD, Kauppinen R, Langendonk JG, Desnick RJ, Deybach JC, Bonkovsky HL, Parker C, Naik H, Badminton M, Stein PE, Minder E, Windyga J, Bruha R, Cappellini MD, Sardh E, Harper P, Sandberg S, Aarsand AK, Andersen J, Alegre F, Ivanova A, Talbi N, Chan A, Querbes W, Ko J, Penz C, Liu S, Lin T, Simon A, Anderson KE
EXPLORE: A prospective, multinational, natural history study of patients with acute hepatic porphyria with recurrent attacks
Background and aims: Acute hepatic porphyria comprises a group of rare genetic diseases caused by mutations in genes involved in heme biosynthesis. Patients can experience acute neurovisceral attacks, debilitating chronic symptoms, and long-term complications. There is a lack of multinational, prospective data characterizing the disease and current treatment practices in severely affected patients.
Approach and results: EXPLORE is a prospective, multinational, natural history study characterizing disease activity and clinical management in patients with acute hepatic porphyria who experience recurrent attacks. Eligible patients had a confirmed acute hepatic porphyria diagnosis and had experienced ≥ 3 attacks in the prior 12 months or were receiving prophylactic treatment. A total of 112 patients were enrolled and followed for at least 6 months. In the 12 months before the study, patients reported a median of 6 acute attacks (range 0–52), with 52 patients (46%) receiving hemin prophylaxis. Chronic symptoms were reported by 73 patients (65%), with 52 patients (46%) experiencing these daily. During the study, 98 patients (88%) experienced a total of 483 attacks, 77% of which required treatment at a health care facility and/or hemin administration (median annualized attack rate 2.0 [range 0.0–37.0]). Elevated levels of hepatic δ-aminolevulinic acid synthase 1 messenger ribonucleic acid levels, δ-aminolevulinic acid, and porphobilinogen compared with the upper limit of normal in healthy individuals were observed at baseline and increased further during attacks. Patients had impaired quality of life and increased health care utilization.
Conclusions: Patients experienced attacks often requiring treatment in a health care facility and/or with hemin, as well as chronic symptoms that adversely influenced day-to-day functioning. In this patient group, the high disease burden and diminished quality of life highlight the need for novel therapies.
Prof. Dr. L. Gouya, Centre de Référence Maladies Rares Porphyries, Service de Biochimie Métabolisme et Nutrition, CHU Paris Nord-Val de Seine – Hôpital Louis Mourier, 178, rue des Renouillers, 92700 Colombes, France, E-Mail: email@example.com
Levitsky J, Asrani SK, Klintmalm G, Schiano T, Moss A, Chavin K, Miller C, Guo K, Zhao L, Jennings LW, Brown M, Armstrong B, Abecassis M
Discovery and validation of a biomarker model (PRESERVE) predictive of renal outcomes after liver transplantation
Background and aims: A high proportion of patients develop chronic kidney disease (CKD) after liver transplantation (LT). The authors aimed to develop clinical/protein models to predict future glomerular filtration rate (GFR) deterioration in this population.
Approach and results: In independent multicenter discovery (CTOT14) and single-center validation (BUMC) cohorts, they analyzed kidney injury proteins in serum/plasma samples at month 3 after LT in recipients with preserved GFR who demonstrated subsequent GFR deterioration versus preservation by year 1 and year 5 in the BUMC cohort. In CTOT14, they also examined correlations between serial protein levels and GFR over the first year. A month 3 predictive model was constructed from clinical and protein level variables using the CTOT14 cohort (n = 60). Levels of β2 microglobulin and CD40 antigen and presence of hepatitis C virus (HCV) infection predicted early (year 1) GFR deterioration (area under the curve [AUC] 0.814). The authors observed excellent validation of this model (AUC 0.801) in the BUMC cohort (n = 50) who had both early and late (year 5) GFR deterioration. At an optimal threshold, the model had the following performance characteristics in CTOT14 and BUMC, respectively: accuracy (0.75, 0.8), sensitivity (0.71, 0.67), specificity (0.78, 0.88), positive predictive value (0.74, 0.75), and negative predictive value (0.76, 0.82). In the serial CTOT14 analysis, several proteins, including β2 microglobulin and CD40, correlated with GFR changes over the first year.
Conclusions: We have validated a clinical/protein model (PRESERVE) that early after liver transplantation can predict future renal deterioration versus preservation with high accuracy. This model may help select recipients at higher risk for subsequent chronic kidney disease for early, proactive renal sparing strategies.
J. Levitsky, M.D., Professor of Medicine, Division of Gastroenterology and Hepatology, Comprehensive Transplant Center, Northwestern University Feinberg School of Medicine, NMH/Arkes Family Pavilion, 19th Floor, 676 North Saint Clair, Chicago, IL 60611, USA, E-Mail: firstname.lastname@example.org
Am J Gastroenterol. 2020;115(5):671–8
Khan MA, Yuan Y, Iqbal U, Kamal S, Khan M, Khan Z, Lee WM, Howden CW
No association linking short-term proton-pump inhibitor use to dementia: Systematic review and meta-analysis of observational studies
Introduction: Long-term use of proton-pump inhibitors (PPIs) has been associated with a wide variety of potentially serious adverse effects including a possible increased risk of dementia. Studies evaluating this association have reached divergent conclusions. The authors aimed to evaluate this proposed association further and to assess the quality of the evidence in its support.
Methods: They searched Medline, Embase, ISI Web of Science, and Cochrane databases for studies examining a link between PPI use and dementia, up to February 2019. Studies reporting summary results as hazard ratio (HR) or odds ratio (OR) were pooled using the DerSimonian and Laird random-effects model for meta-analyses. Methodological quality of individual observational studies was assessed using the Newcastle-Ottawa scale and the overall quality of evidence rated as per the GRADE approach.
Results: The authors identified and included 11 observational studies comprising 642,949 subjects; 64% were women. Most studies were short-term ranging from 5–10 years. There were 158,954 PPI users and 483,995 non-users. For studies summarizing data as adjusted HR, pooled HR for all causes of dementia was 1.10 (0.88–1.37); for Alzheimer dementia only, it was 1.06 (0.72–1.55). For studies summarizing data as adjusted OR, pooled OR for all causes of dementia was 1.03 (0.84–1.25) and for Alzheimer dementia only 0.96 (0.82–1.11). Per Newcastle-Ottawa scale assessment, 10 studies were of high quality and 1 was of moderate quality. By applying GRADE methodology, quality of evidence for both outcomes was very low.
Discussion: No evidence was found to support the proposed association between proton-pump inhibitor (PPI) use and an increased risk of dementia. PPI use among patients who have a valid indication for it, should not be curtailed because of concerns about dementia risk.
C.W. Howden, M.D., Professor of Medicine, Division of Gastroenterology and Hepatology, University of Tennessee Health Science Center, 956 Court Avenue, Suit H210, Memphis, TN 38163, USA, E-Mail: email@example.com
N Engl J Med. 2020;382(14):1299–308
Lau JYW, Yu Y, Tang RSY, Chan HCH, Yip HC, Chan SM, Luk SWY, Wong SH, Lau LHS, Lui RN, Chan TT, Mak JWY, Chan FKL, Sung JJY
Timing of endoscopy for acute upper gastrointestinal bleeding
Background: It is recommended that patients with acute upper gastrointestinal bleeding undergo endoscopy within 24 hours after gastroenterological consultation. The role of endoscopy performed within time frames shorter than 24 hours has not been adequately defined.
Methods: To evaluate whether urgent endoscopy improves outcomes in patients predicted to be at high risk for further bleeding or death, the authors randomly assigned patients with overt signs of acute upper gastrointestinal bleeding and a Glasgow-Blatchford score of 12 or higher (scores range from 0–23, with higher scores indicating a higher risk of further bleeding or death) to undergo endoscopy within 6 hours (urgent-endoscopy group) or between 6 and 24 hours (early-endoscopy group) after gastroenterological consultation. The primary end point was death from any cause within 30 days after randomization.
Results: A total of 516 patients were enrolled. The 30-day mortality was 8.9% (23/258 patients) in the urgent-endoscopy group and 6.6% (17/258) in the early-endoscopy group (difference, 2.3 percentage points; 95% confidence interval [CI]: -2.3–6.9). Further bleeding within 30 days occurred in 28 patients (10.9%) in the urgent-endoscopy group and in 20 (7.8%) in the early-endoscopy group (difference, 3.1 percentage points; 95% CI: -1.9-8.1). Ulcers with active bleeding or visible vessels were found on initial endoscopy in 105 of the 158 patients (66.4%) with peptic ulcers in the urgent-endoscopy group and in 76 of 159 (47.8%) in the early-endoscopy group. Endoscopic hemostatic treatment was administered at initial endoscopy for 155 patients (60.1%) in the urgent-endoscopy group and for 125 (48.4%) in the early-endoscopy group.
Conclusions: In patients with acute upper gastrointestinal bleeding who were at high risk for further bleeding or death, endoscopy performed within 6 hours after gastroenterological consultation was not associated with lower 30-day mortality than endoscopy performed between 6 and 24 hours after consultation.
Prof. Dr. J.Y.W. Lau, Department of Surgery, Rm. 64026, Lui Chee Woo Clinical Science Bldg., Prince of Wales Hospital, 32 Ngan Shing St., Shatin, Hong Kong, E-Mail: firstname.lastname@example.org
Suzuki S, Gotoda T, Kusano C, Ikehara H, Ichijima R, Ohyauchi M, Ito H, Kawamura M, Ogata Y, Ohtaka M, Nakahara M, Kawabe K
Seven-day vonoprazan and low-dose amoxicillin dual therapy as first-line Helicobacter pylori treatment: A multicenter randomized trial in Japan
Objective: To date, no randomized trials have compared the efficacy of vonoprazan and amoxicillin dual therapy with other standard regimens for Helicobacter pylori treatment. This study aimed to investigate the efficacy of the 7-day vonoprazan and low-dose amoxicillin dual therapy as a first-line H. pylori treatment, and compared this with vonoprazan-based triple therapy.
Design: This prospective, randomized clinical trial was performed at 7 Japanese institutions. Patients with H. pylori-positive culture test and naive to treatment were randomly assigned in a 1:1 ratio to either VA-dual therapy (vonoprazan 20 mg + amoxicillin 750 mg twice daily) or VAC-triple therapy (vonoprazan 20 mg + amoxicillin 750 mg + clarithromycin 200 mg twice daily) for 7 days, with stratification by age, sex, H. pylori antimicrobial resistance and institution. Eradication success was evaluated by 13C-urea breath test at least 4 weeks after treatment.
Results: Between October 2018 and June 2019, 629 subjects were screened and 335 were randomized. The eradication rates of VA-dual and VAC-triple therapies were 84.5% and 89.2% (p = 0.203) by intention-to-treat analysis, respectively, and 87.1% and 90.2% (p = 0.372) by per-protocol analysis, respectively. VA-dual was non-inferior to VAC-triple in the per-protocol analysis. The eradication rates in strains resistant to clarithromycin for VA-dual were significantly higher than those for VAC-triple (92.3% vs. 76.2%; p = 0.048). The incidence of adverse events was equal between groups.
Conclusion: The 7-day vonoprazan and low-dose amoxicillin dual therapy provided acceptable Helicobacter pylori eradication rates and a similar effect to vonoprazan-based triple therapy in regions with high clarithromycin resistance.
Prof. Dr. T. Gotoda, Division of Gastroenterology and Hepatology, Department of Medicine, Nihon University School of Medicine, Tokyo 101-8309, Japan, E-Mail: email@example.com
Lancet Oncol. 2020;21(4):508–18
Pishvaian MJ, Blais EM, Brody JR, Lyons E, DeArbeloa P, Hendifar A, Mikhail S, Chung V, Sahai V, Sohal DPS, Bellakbira S, Thach D, Rahib L, Madhavan S, Matrisian LM, Petricoin EF
Overall survival in patients with pancreatic cancer receiving matched therapies following molecular profiling: A retrospective analysis of the Know Your Tumor registry trial
Background: About 25% of pancreatic cancers harbor actionable molecular alterations, defined as molecular alterations for which there is clinical or strong preclinical evidence of a predictive benefit from a specific therapy. The Know Your Tumor (KYT) program includes U.S. patients with pancreatic cancer and enables patients to undergo commercially available multi-omic profiling to provide molecularly tailored therapy options and clinical trial recommendations. The authors sought to determine whether patients with pancreatic cancer whose tumors harbored such actionable molecular alterations and who received molecularly matched therapy had a longer median overall survival than similar patients who did not receive molecularly matched therapy.
Methods: In this retrospective analysis, treatment history and longitudinal survival outcomes were analyzed in patients aged 18 years or older with biopsy-confirmed pancreatic cancer of any stage, enrolled in the KYT program and who received molecular testing results. Since the timing of KYT enrolment varied for each patient, the primary outcome measurement of median overall survival was calculated from the initial diagnosis of advanced disease until death. They compared median overall survival in patients with actionable mutations who were treated with a matched therapy versus those who were not treated with a matched therapy.
Findings: Of 1856 patients with pancreatic cancer who were referred to the KYT program between June 16, 2014, and March 31, 2019, 1082 patients (58%) received personalized reports based on their molecular testing results. Actionable molecular alterations were identified in 282 of 1082 samples (26%). Among 677 patients for whom outcomes were available, 189 had actionable molecular alterations. With a median follow-up of 383 days (IQR 214–588), those patients with actionable molecular alterations who received a matched therapy (n = 46) had significantly longer median overall survival than did those patients who only received unmatched therapies (n = 143; 2.58 years [95% CI: 2.39 to not reached] vs. 1.51 years [95% CI: 1.33–1.87]; hazard ratio [HR] = 0.42 [95% CI: 0.26–0.68], p = 0.0004). The 46 patients who received a matched therapy also had significantly longer overall survival than the 488 patients who did not have an actionable molecular alteration (2.58 years [95% CI: 2.39 to not reached] vs. 1.32 years [95% CI: 1.25–1.47]; HR = 0.34 [95% CI: 0.22–0.53], p < 0.0001). However, median overall survival did not differ between the patients who received unmatched therapy and those without an actionable molecular alteration (HR = 0.82 [95% CI: 0.64–1.04], p = 0.10).
Interpretation: These real-world outcomes suggest that the adoption of precision medicine can have a substantial effect on survival in patients with pancreatic cancer, and that molecularly guided treatments targeting oncogenic drivers and the DNA damage response and repair pathway warrant further prospective evaluation.
M.J. Pishvaian, M.D., Associate Professor, Department of Gastrointestinal Medical Oncology, The University of Texas, MD Anderson Cancer Center, Houston, TX 77030, USA, E-Mail: firstname.lastname@example.org