Showing papers in "Digestive Diseases and Sciences in 2017"
TL;DR: Currently, NASH is the most rapidly growing indication for LT in the US, despite resurgence in ALD, and NASH remains the second leading indication forLT.
Abstract: Nonalcoholic steatohepatitis (NASH) is a rapidly growing etiology of end-stage liver disease in the US. Temporal trends and outcomes in NASH-related liver transplantation (LT) in the US were studied. A retrospective cohort study utilizing the United Network for Organ Sharing and Organ Procurement and Transplantation (UNOS/OPTN) 2003–2014 database was conducted to evaluate the frequency of NASH-related LT. Etiology-specific post-transplant survival was evaluated with Kaplan–Meier methods and multivariate Cox proportional hazards models.
Overall, 63,061 adult patients underwent LT from 2003 to 2014, including 20,782 HCV (32.96%), 9470 ALD (15.02%), and 8262 NASH (13.11%). NASH surpassed ALD and became the second leading indication for LT beginning in 2008, accounting for 17.38% of LT in 2014. From 2003 to 2014, the number of LT secondary to NASH increased by 162%, whereas LT secondary to HCV increased by 33% and ALD increased by 55%. Due to resurgence in ALD, the growth in NASH and ALD was comparable from 2008 to 2014 (NASH +50.15% vs. ALD +41.87%). The post-transplant survival in NASH was significantly higher compared to HCV (5-year survival: NASH −77.81%, 95% CI 76.37–79.25 vs. HCV −72.15%, 95% CI 71.37–72.93, P < .001). In the multivariate Cox proportional hazards model, NASH demonstrated significantly higher post-transplant survival compared to HCV (HR 0.75; 95% CI 0.71–0.79, P < .001).
Currently, NASH is the most rapidly growing indication for LT in the US. Despite resurgence in ALD, NASH remains the second leading indication for LT.
186 citations
TL;DR: A systematic review and meta-analysis to determine the clinical success and safety of POEM in SEDs found that it is an effective and safe therapeutic modality for the treatment of spastic esophageal disorders.
Abstract: Spastic esophageal disorders (SEDs) include spastic achalasia (type III), diffuse esophageal spasm (DES), and nutcracker/jackhammer esophagus (JH). Per-oral endoscopic myotomy (POEM) has demonstrated efficacy and safety in the treatment of achalasia. Recently, POEM has been indicated for the treatment of SEDs. We conducted a systematic review and meta-analysis to determine the clinical success and safety of POEM in SEDs. We searched several databases from 01/01/2007 to 01/10/2016 to identify studies (with five or more patients) on POEM for the treatment of SEDs. Weighted pooled rates (WPRs) for clinical success and adverse events (AEs) were calculated for all SEDs. Clinical success was defined as Eckardt scores of ≤3 and/or improvement in severity of dysphagia based on achalasia disease-specific health-related quality of life questionnaire. The WPRs for clinical success and AEs were analyzed using fixed- or random-effects model based on heterogeneity. The proportionate difference in clinical success and post-procedure adverse event rates among individual types of SEDs was also calculated. A total of eight observational studies with 179 patients were included in the final analysis. Two studies were of good quality and six were of fair quality based on the National Institutes of Health quality assessment tool. The WPR with 95% confidence interval (CI) for cumulative clinical success of POEM in all SEDs was 87% (78, 93%), I
2 = 37%. The total number of patients for individual disorders, i.e., type III achalasia, JH, and DES, was 116, 37, and 18, respectively. The WPRs for clinical success of POEM for type III achalasia, DES, and JH were 92, 88, and 72%, respectively. Proportion difference of WPR for clinical success was significantly higher for type III achalasia in comparison with JH (20%, P = 0.01). The WPR with 95% CI for AEs of POEM in all SEDs was 14% (9, 20%), I
2 = 0%. The WPRs for post-procedure adverse events for type III achalasia, DES, and JH were 11, 14, and 16%, respectively. There was no difference in safety of POEM among individual SEDs. POEM is an effective and safe therapeutic modality for the treatment of spastic esophageal disorders.
143 citations
TL;DR: The trends of CRC in China over the past decade are presented, which reveals the domestic diversity of age, gender, and geography and finds the differences between China and developed countries, which may yield insights for national programs and policies.
Abstract: Due to the changes in lifestyle and dietary behaviors, the incidence of colorectal cancer (CRC) has been rapidly increasing in China This study is to present the trends of CRC in China over the past decade It used a series of nationally representative data, including the National Central Cancer Registry of China, the GLOBOCAN project and the Global Burden of Disease The age-standardized rate of CRC incidence increased from 128 in 2003 to 168 per 100,000 in 2011, while the mortality rose from 59 to 78 per 100,000 The age group most affected by incident CRC cases were those aged 60–74 years old, whereas CRC death was most associated with those >74 years Furthermore, the east coast of China presented a higher mortality rate (>15 and 10–149 per 100,000 in men and women) than central and west China (5–149 and 5–99 per 100,000) Compared with other countries worldwide, China indicated lower rates of incidence (142 per 100,000), mortality (74 per 100,000), and 5-year prevalence (527 per 100,000) than most developed countries However, China had a higher case-fatality ratio (140 %) and mortality/incidence ratio (521 %) Lastly, disability-adjusted life years attributed to CRC in China was 2242 per 100,000 It presents a steady increase in CRC in China over the past decade It also reveals the domestic diversity of age, gender, and geography and finds the differences between China and developed countries, which may yield insights for national programs and policies
137 citations
TL;DR: In this study of moderately active Crohn’s disease, CBD was safe but had no beneficial effects, which could be due to the small dose of CBD, the small number of patients in the study, or the lack of the necessary synergism with other cannabinoids.
Abstract: Cannabidiol (CBD) is an anti-inflammatory cannabinoid shown to be beneficial in a mouse model of IBD. Lacking any central effect, cannabidiol is an attractive option for treating inflammatory diseases. To assess the effects of cannabidiol on Crohn’s disease in a randomized placebo-controlled trial. Twenty patients aged 18–75 years with a Crohn’s disease activity index (CDAI) >200 were randomized to receive oral (10 mg) CBD or placebo twice daily. Patients did not respond to standard treatment with steroids (11 patients), thiopurines (14), or TNF antagonists (11). Disease activity and laboratory parameters were assessed during 8 weeks of treatment and 2 weeks thereafter. Other medical treatment remained unchanged. Of 20 patients recruited 19 completed the study. Their mean age was 39 ± 15, and 11 were males. The average CDAI before cannabidiol consumption was 337 ± 108 and 308 ± 96 (p = NS) in the CBD and placebo groups, respectively. After 8 weeks of treatment, the index was 220 ± 122 and 216 ± 121 in the CBD and placebo groups, respectively (p = NS). Hemoglobin, albumin, and kidney and liver function tests remained unchanged. No side effects were observed. In this study of moderately active Crohn’s disease, CBD was safe but had no beneficial effects. This could be due to lack of effect of CBD on Crohn’s disease, but could also be due to the small dose of CBD, the small number of patients in the study, or the lack of the necessary synergism with other cannabinoids. Further investigation is warranted. NCT01037322.
133 citations
TL;DR: Key genetic and biochemical features of the trypsin-dependent pathological pathway in chronic pancreatitis are reviewed.
Abstract: Genetic investigations have provided unique insight into the mechanism of chronic pancreatitis in humans and firmly established that uncontrolled trypsin activity is a central pathogenic factor. Mutations in the PRSS1, SPINK1, and CTRC genes promote increased activation of trypsinogen to trypsin by stimulation of autoactivation or by impairing protective trypsinogen degradation and/or trypsin inhibition. Here we review key genetic and biochemical features of the trypsin-dependent pathological pathway in chronic pancreatitis.
124 citations
TL;DR: Future studies should focus on providing more precise estimates of the risk of disease transition in a cohort of patients, quantification of clinical events during the natural course of disease, and discovery of biomarkers of the different stages of the disease continuum.
Abstract: Emerging data in the past few years suggest that acute, recurrent acute (RAP), and chronic pancreatitis (CP) represent a disease continuum. This review discusses the similarities and differences in the epidemiology of RAP and CP. RAP is a high-risk group, comprised of individuals at varying risk of progression. The premise is that RAP is an intermediary stage in the pathogenesis of CP, and a subset of RAP patients during their natural course transition to CP. Although many clinical factors have been identified, accurately predicting the probability of disease course in individual patients remains difficult. Future studies should focus on providing more precise estimates of the risk of disease transition in a cohort of patients, quantification of clinical events during the natural course of disease, and discovery of biomarkers of the different stages of the disease continuum. Availability of clinically relevant endpoints and linked biomarkers will allow more accurate prediction of the natural course of disease over intermediate- or long-term-based characteristics of an individual patient. These endpoints will also provide objective measures for use in clinical trials of interventions that aim to alter the natural course of disease.
114 citations
TL;DR: Gaps in knowledge are identified that are necessary to address to improve patient outcomes in pancreatitis and the diseases that are often linked with pancreatitis including diabetes mellitus and pancreatic cancer.
Abstract: This paper reviews the current status of our understanding of the epidemiology, diagnosis, and management of the continuum of pancreatic diseases from acute and recurrent acute pancreatitis to chronic pancreatitis and the diseases that are often linked with pancreatitis including diabetes mellitus and pancreatic cancer. In addition to reviewing the current state of the field, we identify gaps in knowledge that are necessary to address to improve patient outcomes in these conditions.
94 citations
TL;DR: Hydrogen sulfide in the intestinal biosystem may be beneficial to bacteria by increasing resistance to antibiotics, and protecting them from reactive oxygen species, but at elevated concentrations may become toxic to the host.
Abstract: In this review, we focus on the activities transpiring in the anaerobic segment of the sulfur cycle occurring in the gut environment where hydrogen sulfide is produced. While sulfate-reducing bacteria are considered as the principal agents for hydrogen sulfide production, the enzymatic desulfhydration of cysteine by heterotrophic bacteria also contributes to production of hydrogen sulfide. For sulfate-reducing bacteria respiration, molecular hydrogen and lactate are suitable as electron donors while sulfate functions as the terminal electron acceptor. Dietary components provide fiber and macromolecules that are degraded by bacterial enzymes to monomers, and these are fermented by intestinal bacteria with the production to molecular hydrogen which promotes the metabolic dominance by sulfate-reducing bacteria. Sulfate is also required by the sulfate-reducing bacteria, and this can be supplied by sulfate- and sulfonate-containing compounds that are hydrolyzed by intestinal bacterial with the release of sulfate. While hydrogen sulfide in the intestinal biosystem may be beneficial to bacteria by increasing resistance to antibiotics, and protecting them from reactive oxygen species, hydrogen sulfide at elevated concentrations may become toxic to the host.
85 citations
TL;DR: The current understanding of the mechanisms and management of these complications of chronic pancreatitis are reviewed.
Abstract: Chronic pancreatitis is a disease that leads to irreversible changes in the pancreatic morphology and function. The loss of function can lead to diabetes mellitus and exocrine pancreatic insufficiency. The inflammation and fibrosis can also lead to other complications including a chronic abdominal pain syndrome, metabolic bone disease, and pancretic cancer. This article reviews our current understanding of the mechanisms and management of these complications of chronic pancreatitis.
82 citations
TL;DR: DAA therapy significantly decreased recurrence rate when it was performed after initial HCC therapy, and Multivariate analysis showed DAA Therapy significantly decreasedRecurrence rate with a hazard ratio of 0.353 after adjustment with covariates of tumor multiplicity, alpha-fetoprotein value, and prothrombin time.
Abstract: Suppressive activity of recurrence by interferon-free direct-acting antivirals (DAA) is not elucidated after curative treatment of hepatocellular carcinoma (HCC). A total of 177 patients received DAA after curative manners of HCC: 89 patients underwent DAA therapy after initial HCC treatment, and the other 88 patients after repeated therapy of 2–10 times. Among a cohort of HCC patients with surgery and radiofrequency ablation, 89 patients were chosen adjusting age, gender, and Barcelona Clinic Liver Cancer (BCLC) staging with 89 patients with initial HCC therapy. HCC recurrence rates at the end of first and second year were 18.1 and 22.1% in patients with once of HCC therapy, 28.2 and 41.6% in those with 2–3 times of therapy, and 60.2 and 74.5% in those with 4 or more times of therapy, respectively (P < 0.0001). Recurrence rates were compared between 89 patients with DAA therapy after initial HCC therapy and 89 age-, gender-, and BCLC staging-matched patients without antiviral therapy after initial HCC therapy. HCC recurrence rates at first and second year were 18.1 and 25.0% in patients with DAA therapy and 21.8 and 46.5% in those without DAA therapy, respectively (P = 0.003). Multivariate analysis showed DAA therapy significantly decreased recurrence rate with a hazard ratio of 0.353 (confidence interval: 0.191–0.651) after adjustment with covariates of tumor multiplicity, alpha-fetoprotein value, and prothrombin time. DAA therapy significantly decreased recurrence rate when it was performed after initial HCC therapy.
81 citations
TL;DR: ColonFlag® identifies individuals with tenfold higher risk of undiagnosed colorectal cancer at curable stages (0/I/II), flags coloreCTal tumors 180–360 days prior to usual clinical diagnosis, and is more accurate at identifying right-sided (compared to left-sided) colorectoral cancers.
Abstract: Machine learning tools identify patients with blood counts indicating greater likelihood of colorectal cancer and warranting colonoscopy referral. To validate a machine learning colorectal cancer detection model on a US community-based insured adult population. Eligible colorectal cancer cases (439 females, 461 males) with complete blood counts before diagnosis were identified from Kaiser Permanente Northwest Region’s Tumor Registry. Control patients (n = 9108) were randomly selected from KPNW’s population who had no cancers, received at ≥1 blood count, had continuous enrollment from 180 days prior to the blood count through 24 months after the count, and were aged 40–89. For each control, one blood count was randomly selected as the pseudo-colorectal cancer diagnosis date for matching to cases, and assigned a “calendar year” based on the count date. For each calendar year, 18 controls were randomly selected to match the general enrollment’s 10-year age groups and lengths of continuous enrollment. Prediction performance was evaluated by area under the curve, specificity, and odds ratios. Area under the receiver operating characteristics curve for detecting colorectal cancer was 0.80 ± 0.01. At 99% specificity, the odds ratio for association of a high-risk detection score with colorectal cancer was 34.7 (95% CI 28.9–40.4). The detection model had the highest accuracy in identifying right-sided colorectal cancers. ColonFlag® identifies individuals with tenfold higher risk of undiagnosed colorectal cancer at curable stages (0/I/II), flags colorectal tumors 180–360 days prior to usual clinical diagnosis, and is more accurate at identifying right-sided (compared to left-sided) colorectal cancers.
TL;DR: Progress in understanding the mechanisms for pain and when this occurs in the natural history, together with assessing new therapies both pharmacological and endoscopic, will enable individualized care and may improve patients' quality of life and survival.
Abstract: Pain affects approximately 80% of patients with pancreatic cancer, with half requiring strong opioid analgesia, namely: morphine-based drugs on step three of the WHO analgesic ladder (as opposed to the weak opioids: codeine and tramadol). The presence of pain is associated with reduced survival. This article reviews the literature regarding pain: prevalence, mechanisms, pharmacological, and endoscopic treatments and identifies areas for research to develop individualized patient pain management pathways. The online literature review was conducted through: PubMed, Clinical Key, Uptodate, and NICE Evidence. There are two principal mechanisms for pain: pancreatic duct obstruction and pancreatic neuropathy which, respectively, activate mechanical and chemical nociceptors. In pancreatic neuropathy, several histological, molecular, and immunological changes occur which correlate with pain including: transient receptor potential cation channel activation and mast cell infiltration. Current pain management is empirical rather etiology-based and is informed by the WHO analgesic ladder for first-line therapies, and then endoscopic ultrasound-guided celiac plexus neurolysis (EUS-CPN) in patients with resistant pain. For EUS-CPN, there is only one clinical trial reporting a benefit, which has limited generalizability. Case series report pancreatic duct stenting gives effective analgesia, but there are no clinical trials. Progress in understanding the mechanisms for pain and when this occurs in the natural history, together with assessing new therapies both pharmacological and endoscopic, will enable individualized care and may improve patients’ quality of life and survival.
TL;DR: This parameter could be useful for the diagnosis and the follow-up of obese patients and in multivariate analysis, a low CAP value with XL probe was negatively associated with waist circumference, triglycerides, albumin, and the alcohol consumption, and positively with alkaline phosphatases.
Abstract: Controlled attenuation parameter (CAP) is a new method for the diagnosis of steatosis Until now, CAP was available only with the M probe of the Fibroscan The aim of this study was to evaluate the diagnostic performance of CAP with the XL probe versus CAP with the M probe, using liver biopsy (LB) as gold standard A total of 236 patients with chronic liver disease undergoing LB had CAP measurement with M and XL probes the same day All LB were analyzed independently by two experienced pathologists Median CAP was 2405 and 2395 dB/m with the M and XL probes, respectively For the detection of steatosis grade with the M and XL probes, AUROCs were 082/083 for S ≥ 1, 089/088 for S ≥ 2, and 092/093 for S3, respectively Cutoffs were (M and XL probes) 246/242 for S ≥ 1, 269/267 for S ≥ 2, and 285/286 dB/m for S3, respectively The factor significantly associated with CAP with the M and XL probes was steatosis grade In multivariate analysis, a low CAP value with XL probe was negatively associated with waist circumference, triglycerides, albumin, and the alcohol consumption, and positively with alkaline phosphatases In multivariate analysis, a high CAP value with the XL probe was positively associated with waist circumference and triglycerides CAP with the XL probe is a new tool for the diagnosis of steatosis This parameter could be useful for the diagnosis and the follow-up of obese patients
TL;DR: In China, the prevalence of H. pylori primary resistance to clarithromycin, metronidazole, and levofloxacin was high and increased over time, whereas the resistance rates to amoxicillin, tetracycline, and furazolidone were low and stable over time.
Abstract: Antibiotic resistance is the most important factor leading to the failure of eradication regimens; thus, it is important to obtain regional antibiotic resistance information. This review focuses on the prevalence of Helicobacter pylori primary resistance to clarithromycin, metronidazole, amoxicillin, levofloxacin, tetracycline, and furazolidone in China. We searched the PubMed, EMBASE, the China National Knowledge Infrastructure, and Chinese Biomedical databases from the earliest date of each database to October 2016. The search terms included the following: H. pylori, antibiotic (including clarithromycin, metronidazole, amoxicillin, levofloxacin, tetracycline, and furazolidone) resistance with or without China or different regions of China. The data analysis was performed using MedCalc 15.2.2. Each article was weighted according to the number of isolated H. pylori strains. A pooled proportion analysis was performed. Twenty-three studies (14 studies in English and 9 in Chinese) were included in this review. A total of 6274, 6418, 3921, 5468, 2802, and 275 H. pylori strains were included in this review to evaluate the prevalence of H. pylori primary resistance to clarithromycin, metronidazole, levofloxacin, amoxicillin, tetracycline, and furazolidone, respectively. Overall, the primary resistance rates of clarithromycin, metronidazole, levofloxacin, amoxicillin, tetracycline, and furazolidone were 28.9, 63.8, 28.0, 3.1, 3.9, and 1.7%, respectively. In China, the prevalence of H. pylori primary resistance to clarithromycin, metronidazole, and levofloxacin was high and increased over time, whereas the resistance rates to amoxicillin, tetracycline, and furazolidone were low and stable over time.
TL;DR: This large series of patients with gastroparesis describes their burdens, concerns, and QOL, finding that Nausea, vomiting, early satiety, and abdominal pain are important symptoms for treatment.
Abstract: The impact of gastroparesis on patients from the patient’s viewpoint is needed to better address treatment priorities. The aims of this study were to: (1) Delineate burdens and concerns of patients with gastroparesis; (2) investigate specific symptoms contributing to impaired quality of life (QOL) in gastroparesis. The International Foundation for Functional GI Disorders gastroparesis survey questionnaire was developed to describe patients’ viewpoint about their experience with gastroparesis and included Patient Assessment of Upper GI Symptoms (PAGI-SYM) and SF-36 QOL survey. A total of 1423 adult patients with gastroparesis completed the survey. Average duration of gastroparesis symptoms was 9.3 years with time from onset to diagnosis 5.0 years. Patients felt that they receive good information regarding treatment options from physicians, the Internet, and Facebook. Patients rated their satisfaction with available treatment for their gastroparesis as dissatisfied (33%), somewhat dissatisfied (27%), neutral (14%), somewhat satisfied (15%), and satisfied (4%). Patients felt that gastroparesis symptoms that are most important to improve with treatment are nausea, stomach pain, and vomiting. Overall, there was a decreased quality of life by SF-36. Physical health QOL score was negatively correlated with symptoms including nausea (r = −0.37), upper abdominal pain (r = −0.37), and early satiety (r = −0.37). This large series of patients with gastroparesis describes their burdens, concerns, and QOL. Nausea, vomiting, early satiety, and abdominal pain are important symptoms for treatment. Many patients are not satisfied with current treatments, wanting specific treatments for their disorder. Interestingly, a large number of patients find out about treatments, not only from their physician, but also using the Internet including social media.
TL;DR: Although it cannot be considered the gold-standard method for the functional diagnosis of PEI, the advantages of the FE-1 test make it a very appropriate test for screening patients who may be at risk of this disorder.
Abstract: The early diagnosis of pancreatic exocrine insufficiency (PEI) is hindered because many of the functional diagnostic techniques used are expensive and require specialized facilities, which prevent their widespread availability. We have reviewed current evidence in order to compare the utility of these functional diagnostic techniques with the fecal elastase-1 (FE-1) test in the following three scenarios: screening for PEI in patients presenting with symptoms suggestive of pancreatic disease, such as abdominal pain or diarrhea; determining the presence of PEI in patients with an established diagnosis of pancreatic disease, such as chronic pancreatitis or cystic fibrosis; determining exocrine status in disorders not commonly tested for PEI, but which have a known association with this disorder. Evidence suggests the FE-1 test is reliable for the evaluation of pancreatic function in many pancreatic and non-pancreatic disorders. It is non-invasive, is less time-consuming, and is unaffected by pancreatic enzyme replacement therapy. Although it cannot be considered the gold-standard method for the functional diagnosis of PEI, the advantages of the FE-1 test make it a very appropriate test for screening patients who may be at risk of this disorder.
TL;DR: Recognizing that the clinical manifestations of HHT can involve a number of organ systems will provide clinicians with a higher index of suspicion for the disease and greatly reduce mortality for a patient with HHT through appropriate screening for complications.
Abstract: Hereditary hemorrhagic telangiectasia (HHT), also called Osler-Weber-Rendu syndrome, is an autosomal dominant genetic disease that affects the vasculature of numerous organs. The prevalence of HHT is estimated to be between 1.5 and 2 persons per 10,000. While there is still much to learn about this condition, there is an increasing understanding its underlying pathophysiology, genetic basis, presentations, and management. Recognizing that the clinical manifestations of HHT can involve a number of organ systems will provide clinicians with a higher index of suspicion for the disease. This early diagnosis and genotyping can greatly reduce mortality for a patient with HHT through appropriate screening for complications. This review will focus on the gastrointestinal manifestations of HHT and how these can dictate treatment and prognosis.
TL;DR: NLRP3 inflammasome is activated in CD patients and in UC patients with long-standing disease and IL-1β production was similar between carriers of wild-type and of SNP alleles of the rs2241880.
Abstract: NLRP3 inflammasome is a multimolecular cytosol complex that, when activated, contributes to the cleavage of pro-interleukin (IL)-1β to IL-1β To investigate NLRP3 inflammasome activation in inflammatory bowel disease Peripheral blood mononuclear cells from Crohn’s disease (CD), ulcerative colitis (UC) patients and controls were stimulated with LPS in the absence or presence of MSU After incubation, concentrations of IL-1β, IL-6, and TNFα were measured in cell supernatants and concentration of pro-IL-1β was measured in cell lysates NLRP3 activation was defined as more than 30% increase in IL-1β production after MSU addition In separate experiments, PBMCs were lysed for RNA isolation transcripts of IL-1β, TNFα, NLRP3, and CASP1 were measured by RT-PCR DNA was isolated from CD patients for ATG16L1 gene genotyping
NLRP3 inflammasome was activated in 60% of CD patients compared to 286% of controls (p = 0042); no significant difference was detected between UC and controls Among UC patients, NLRP3 activation was associated (p = 0008) with long-standing disease (>15 years) IL-1β levels were significantly higher in CD patents in comparison with controls (p = 0032) No difference was detected in the levels of IL-6, TNFα, pro-IL-1β and in the numbers IL-1β, TNFα, NLRP3, and CASP1 transcripts among groups IL-1β production was similar between carriers of wild-type and of SNP alleles of the rs2241880
NLRP3 inflammasome is activated in CD patients and in UC patients with long-standing disease
TL;DR: PVT1 might act as a “sponge” to inhibit miR-152 in gastric cancer cells and is a promising molecular target to improve the diagnosis and therapy of GC.
Abstract: PVT1 was up-regulated in patients with gastric cancer (GC) and might be as a novel biomarker for predicting GC. However, the exact mechanism of PVT1 exerting functions in GC was still poorly understood. Emerging evidence suggests that long noncoding RNAs may act as endogenous microRNA (miRNA) sponges to bind to miRNAs and regulate their function. This study aimed to determine the function of PVT1 on miR-152 expression in GC cells. The levels of PVT1 and miR-152 were determined in GC tissues by quantitative real-time PCR. The expression of miR-152 was detected in GC cells transfected with PVT1 plasmid or siPVT1. Luciferase assay was performed to verify the regulation of miR-152 to CD151 or FGF2 expression and PVT1 to miR-152 expression. The effects of PVT1 on the expression of CD151 and FGF2 were evaluated by Western blot. PVT1 was up-regulated in GC tissues than that in the matched normal tissues, and mRNA level of miR-152 was decreased. MiR-152 was negatively associated with PVT1 expression in GC tissues. Based on the in silico analysis, we found that PVT1 have three binding sequences for miR-152. Moreover, PVT1 might inhibit the expression of miR-152 and increased the expression of CD151 and FGF2 through regulating miR-152. PVT1 was positively associated with CD151 and FGF2 expression in GC tissues. PVT1 might act as a “sponge” to inhibit miR-152 in gastric cancer cells. PVT1 is a promising molecular target to improve the diagnosis and therapy of GC.
TL;DR: Being overweight/obese, Mexican–American ethnicity, later study period, older age, and male gender, were associated with higher odds of having CLD.
Abstract: Chronic liver disease (CLD) starts or becomes established in the adolescent and young adult (AYA) age group. This study aimed to estimate trends in CLD prevalence among US AYAs and to assess factors associated with CLD. Cross-sectional data from 14,547 AYAs (population-weighted N = 68,274,386) aged 15–39 years enrolled in the National Health and Nutrition Examination Survey from 1988 to 2012 were used. Nonalcoholic fatty liver disease (NAFLD) was defined as elevated alanine aminotransferase (>19 U/L for females and >30 U/L for males) in subjects with BMI ≥ 25 kg/m2; alcoholic liver disease (ALD) as excessive alcohol use (≥3 drinks/day for men and ≥2 drinks/day for women) and elevated aminotransferases after excluding alternative etiologies. Participants were considered hepatitis C virus (HCV) positive if antibody to HCV and HCV-RNA was positive. There was a sharp increase in the prevalence of CLD from 12.9% in 1988–1994 to 28.5% in 1999–2004 that remained stable after that (27.7%). NAFLD was the most common etiology accounting for 22% of all CLD in the later period. The prevalence of ALD has been steadily increasing throughout the years, while HCV has been decreasing. On multivariate analysis, being overweight/obese, Mexican–American ethnicity, later study period, older age, and male gender, were associated with higher odds of having CLD. More than one quarter of US AYAs might be affected by CLD. CLD prevalence in this age group has more than doubled over the past three decades mainly due to rise in NAFLD prevalence.
TL;DR: Oral supplementation with high-dose vitamin D3 at 10,000 IU daily significantly improved serum 25-hydroxy-vitamin D levels and improvement in anxiety and depression scores and a good safety profile were observed in both groups treated with vitamin D 3.
Abstract: To assess the tolerability and efficacy of high-dose vitamin D3 in patients with Crohn’s disease (CD). This was a randomized, double-blind placebo-controlled trial of high-dose vitamin D3 at 10,000 IU daily (n = 18) compared to 1000 IU daily (n = 16) for 12 months in patients with CD in remission. The primary outcome was change in serum 25-hydroxy-vitamin D levels. Secondary outcomes included clinical relapse rates and changes in mood scores. High-dose vitamin D3 at 10,000 IU daily significantly improved 25-hydroxy-vitamin D levels from a mean of 73.5 nmol/L [standard deviation (SD) 11.7 nmol/L] to 160.8 nmol/L (SD 43.2 nmol/L) (p = 0.02). On an intention-to-treat basis, the rate of relapse was not significantly different between patients receiving low- and high-dose vitamin D3 (68.8 vs 33.3%, p = 0.0844). In per-protocol analysis, clinical relapse of Crohn’s disease was less frequently observed in patients receiving a high dose (0/12 or 0%) compared to those receiving a low dose of 1000 IU daily (3/8 or 37.5%) (p = 0.049). Improvement in anxiety and depression scores and a good safety profile were observed in both groups treated with vitamin D3. Oral supplementation with high-dose vitamin D3 at 10,000 IU daily significantly improved serum 25-hydroxy-vitamin D levels. Rates of clinical relapse were similar between both groups. Larger studies using high-dose vitamin D3 for treatment of inflammatory bowel diseases are warranted. NCT02615288.
TL;DR: Meta-analysis with meta-regression shows initial histologic and symptomatic response rates on the same order of magnitude for topical corticosteroids and six-food elimination diet, but heterogeneity of study designs prevents direct comparison of modalities.
Abstract: Topical corticosteroids or six-food elimination diet is recommended as initial therapy for eosinophilic esophagitis (EoE). We aimed to summarize published manuscripts that report outcomes of these therapies for EoE. We performed a systematic review in MEDLINE, Web of Science, and Embase of published manuscripts describing topical fluticasone, topical budesonide, and six-food elimination diet as therapies for EoE. We conducted meta-analysis of symptom improvement and the change in peak mucosal eosinophil count, with heterogeneity between studies examined with meta-regression analysis. Systematic review yielded 51 articles that met inclusion criteria. Summary histologic response rates were 68.3% [95% prediction limits (PL) 16.2–96.0%] for fluticasone, 76.8% (95% PL 36.1–95.1%) for budesonide, and 69.0% (95% PL 31.9–91.4%) for six-food elimination diet. Corresponding decreases in eosinophil counts were 37.8 (95% PL 19.0–56.7), 62.5 (95% PL 125.6 to −0.67, and 44.6 (95% PL 26.5–62.7), respectively. Symptom response rates were 82.3% (95% PL 68.1–91.1%), 87.9% (95% PL 42.7–98.6%), and 87.3% (95% PL 64.5–96.3%), respectively. Meta-regression analyses decreased the initially large estimate of residual heterogeneity and suggested differences in histologic response rate associated with study populations’ baseline eosinophil count and age. The literature describing topical corticosteroids and six-food elimination diet consists of small studies with diverse methods and population characteristics. Meta-analysis with meta-regression shows initial histologic and symptomatic response rates on the same order of magnitude for topical corticosteroids and six-food elimination diet, but heterogeneity of study designs prevents direct comparison of modalities.
Brigham and Women's Hospital1, Ohio State University2, Virginia Commonwealth University3, Indiana University4, Saint Louis University5, Dartmouth–Hitchcock Medical Center6, University of Michigan7, UAB Hospital8, Mayo Clinic9, University of Florida10, University of Wisconsin-Madison11, University of Pittsburgh12, Medical University of South Carolina13, University of Chicago14
TL;DR: Alcohol remains the most common physician-defined etiology, while smoking was the most commonly identified TIGAR-O risk factor.
Abstract: Our aim was to validate recent epidemiologic trends and describe the distribution of TIGAR-O risk factors in chronic pancreatitis (CP) patients. The NAPS-2 Continuation and Validation (NAPS2-CV) study prospectively enrolled 521 CP patients from 13 US centers from 2008 to 2012. CP was defined by definitive changes in imaging, endoscopy, or histology. Data were analyzed after stratification by demographic factors, physician-defined etiology, participating center, and TIGAR-O risk factors. Demographics and physician-defined etiology in the NAPS2-CV study were similar to the original NAPS2 study. Mean age was 53 years (IQR 43, 62) with 55% males and 87% white. Overall, alcohol was the single most common etiology (46%) followed by idiopathic etiology (24%). Alcohol etiology was significantly more common in males, middle-aged (35–65 years), and non-whites. Females and elderly (≥65 years) were more likely to have idiopathic etiology, while younger patients (<35 years) to have genetic etiology. Variability in etiology was noted by participating centers (e.g., alcohol etiology ranged from 27 to 67% among centers enrolling ≥25 patients). Smoking was the most commonly identified (59%) risk factor followed by alcohol (53%), idiopathic (30%), obstructive (19%), and hyperlipidemia (13%). The presence of multiple TIGAR-O risk factors was common, with 1, 2, ≥3 risk factors observed in 27.6, 47.6, and 23.6% of the cohort, respectively. Our data validate the current epidemiologic trends in CP. Alcohol remains the most common physician-defined etiology, while smoking was the most commonly identified TIGAR-O risk factor. Identification of multiple risk factors suggests CP to be a complex disease.
TL;DR: Among a multicenter cohort of patients with IBD demonstrating primary response to VDZ, the addition of combination therapy with an immunomodulator is a significant predictor of clinical response or remission at week 54 in patients with CD.
Abstract: Vedolizumab (VDZ) has demonstrated long-term efficacy in Crohn’s disease (CD) and ulcerative colitis (UC) in phase III trials. Our aim was to evaluate the efficacy of VDZ at week 54 in inflammatory bowel disease (IBD) in a multicenter cohort of patients. Adult patients completing induction therapy with VDZ were eligible for this study. Clinical response and remission was assessed using the Harvey–Bradshaw Index (HBI) for CD, the Simple Clinical Colitis Activity Index for UC and physician assessment. Among 136 total patients (96 CD and 40 UC), 76 (56%) demonstrated clinical response or remission at week 54. In univariate analysis, for patients with CD concomitant initiation of immunomodulator therapy (2.71, 95% CI 1.11–6.57), the addition of an immunomodulator (OR 11.49, 3.16–41.75) and CRP < 3 (4.92, 95% CI 1.99–12.15) was associated with increased odds of clinical response or remission at week 54. For UC patients, hospitalization after VDZ induction was associated with decreased odds of response or remission at week 54 (OR 0.22, 95% CI 0.05–0.88). On multivariate analysis in CD, addition of an immunomodulator (OR 8.33, 95% CI 2.15–32.26) remained significant predictors of clinical response or remission at week 54. Among a multicenter cohort of patients with IBD demonstrating primary response to VDZ, the addition of combination therapy with an immunomodulator is a significant predictor of clinical response or remission at week 54 in patients with CD.
TL;DR: This study confirms the relationship between BMI and long-term colorectal cancer mortality and indicates that modulation of BMI may reduce risk of CRC mortality.
Abstract: The relationship between dietary and lifestyle risk factors and long-term mortality from colorectal cancer is poorly understood. Several factors, such as obesity, intakes of red meat, and use of aspirin, have been reported to be associated with risk of colorectal cancer mortality, though these findings have not been replicated in all studies to date. In the Minnesota Colon Cancer Control Study, 46,551 participants 50–80 years old were randomly assigned to usual care (control) or annual or biennial screening by fecal occult blood testing. Colon cancer mortality was assessed after 30 years of follow-up. Dietary intake and lifestyle risk factors were assessed by questionnaire at baseline. Age [hazard ratio (HR) 1.09; 95% CI 1.07, −1.11], male sex (HR 1.25; 95% CI 1.01, 1.57), and higher body mass index (BMI) (HR 1.03; 95% CI 1.00–1.05) increased the risk of CRC mortality, while undergoing screening for CRC was associated with a reduced risk of colorectal cancer mortality (HR 0.76; 95% CI 0.61–0.94 and 0.67; 95% CI 0.53–0.83 for biennial and annual screening, respectively). Intakes of grains, meats, proteins, coffee, alcohol, aspirin, fiber, fruits, and vegetables were not associated with colorectal cancer mortality. Our study confirms the relationship between BMI and long-term colorectal cancer mortality. Modulation of BMI may reduce risk of CRC mortality.
TL;DR: While the hepatitis of AN can reach severe levels, a supervised increase in caloric intake and a return to a healthy body weight often quickly lead to normalization of elevated aminotransferases caused by starvation.
Abstract: Anorexia nervosa (AN) has the highest mortality rate of all psychiatric illnesses due to the widespread organ dysfunction caused by the underlying severe malnutrition. Starvation causes hepatocyte injury and death leading to a rise in aminotransferases. Malnutrition-induced hepatitis is common among individuals with AN especially as body mass index decreases. Acute liver failure associated with coagulopathy and encephalopathy can rarely occur. Liver enzymes may also less commonly increase as part of the refeeding process due to hepatic steatosis and can be distinguished from starvation hepatitis by the finding of a fatty liver on ultrasonography. Individuals with AN and starvation-induced hepatitis are at increased risk of hypoglycemia due to depleted glycogen stores and impaired gluconeogenesis. Gastroenterology and hepatology consultations are often requested when patients with AN and signs of hepatitis are hospitalized. It should be noted that additional laboratory testing, imaging, or liver biopsy all have low diagnostic yield, are costly, and potentially invasive, therefore, not generally recommended for diagnostic purposes. While the hepatitis of AN can reach severe levels, a supervised increase in caloric intake and a return to a healthy body weight often quickly lead to normalization of elevated aminotransferases caused by starvation.
TL;DR: Patients who had been diagnosed recently with IBD showed lower rates of surgery and higher rates of immunomodulator and biologic use compared to those reported ever in South Korea.
Abstract: The incidence of inflammatory bowel disease (IBD) is increasing in East Asia; however, population-based data from this region are lacking. We conducted a nationwide, population-based study to examine the incidence and disease course of IBD in South Korea. Using the National Health Insurance claims data, we collected data on patients diagnosed with IBD [10,049 with ulcerative colitis (UC) and 5595 with Crohn’s disease (CD)] from 2011 to 2014. During the study period, the average annual incidence of UC was 5.0 per 105, while that of CD was 2.8 per 105. Among patients with UC, the cumulative rates of surgery 1 and 4 years after diagnosis were 1.0 and 2.0%; those among patients with CD were 9.0 and 13.9%, respectively. The 1- and 4-year cumulative rates of moderate- to high-dose corticosteroid use were, respectively, 26.6 and 45.2% among patients with UC, and 29.9 and 50.8% among those with CD. Similarly, the 1- and 4-year cumulative rates of immunomodulator use were 14.1 and 26.4% among patients with UC, and 58.3 and 76.1% among those with CD, respectively. With regard to biologic use, the 1- and 4-year cumulative rates were 3.0 and 9.0% among patients with UC, and 11.1 and 31.7% among those with CD, respectively. The recent incidence of IBD in South Korea has been the highest in East Asia. Patients who had been diagnosed recently with IBD showed lower rates of surgery and higher rates of immunomodulator and biologic use compared to those reported ever in South Korea.
TL;DR: 1-year data suggest that switching to CT-P13 in Remicade-treated IBD patients is safe and feasible, and disease activity scores and inflammatory markers remained unchanged during follow-up, and no CT- P13-related serious adverse events occurred.
Abstract: Limited data are available on long-term clinical outcomes regarding the switch from Remicade® to the infliximab biosimilar CT-P13 in inflammatory bowel disease (IBD) patients. To investigate long-term efficacy, safety, pharmacokinetic profile, and immunogenicity. We performed a single-center prospective observational cohort study following an elective switch from Remicade® to CT-P13 in IBD patients. Eighty-three patients were included (57 Crohn’s disease, 24 ulcerative colitis, and 2 IBD unclassified), and 68 patients completed one-year follow-up. Disease activity (Harvey–Bradshaw Index and Simple Clinical Colitis Activity Index) as well as inflammatory markers (CRP, fecal calprotectin) did not change significantly during the 1-year follow-up. In total, 7 out of 83 patients (8%) demonstrated detectable antidrug antibodies during follow-up, and 5 out of 7 antidrug antibody titers were already detectable at baseline prior to switching. Six patients (7%) discontinued CT-P13 due to adverse events. Following a switch from Remicade® to CT-P13, 82% of IBD patients continued treatment through 1 year. Disease activity scores and inflammatory markers remained unchanged during follow-up, and no CT-P13-related serious adverse events occurred. These 1-year data suggest that switching to CT-P13 in Remicade®-treated IBD patients is safe and feasible.
TL;DR: The results suggested that CCAT1 functions as an oncogenic lncRNA in ICC, which could serve as a potential diagnostic and therapeutic target for ICC patients.
Abstract: Increasing evidence has suggested that lncRNA CCAT1 is upregulated and functions as a potential tumor promoter in many cancers. However, the potential biological roles and regulatory mechanisms of CCAT1 in intrahepatic cholangiocarcinoma (ICC) remain unclear. We used real-time PCR to measure CCAT1 expression in ICC tissues and the adjacent normal tissues. The statistical analyses were applied to evaluate the prognostic value and associations of CCAT1 expression with clinical parameters. The CCAT1 was silenced with siRNA in ICC cells. The migration and invasion of ICC cells were detected with Transwell assay. The expressions of epithelial–mesenchymal transition (EMT)-related proteins were evaluated to discover whether the process of EMT was involved. We found that CCAT1 expression was elevated in ICC tissues compared to the adjacent normal tissues. We also found that high CCAT1 expression is closely correlated with tumor progression in ICC patients. Furthermore, our results show that knockdown of CCAT1 significantly suppressed the migration and invasion of ICC cells. Additionally, CCAT1 silencing remarkably reverses the EMT phenotype of ICC cells. Moreover, bioinformatics analysis and luciferase reporter assay revealed that CCAT1 directly bound to the miR-152, which has been reported to serve as a tumor suppressor in variety cancers. Further investigation demonstrated that CCAT1 led to the metastasis and EMT activation of ICC cells through inhibiting miR-152. Our results suggested that CCAT1 functions as an oncogenic lncRNA in ICC, which could serve as a potential diagnostic and therapeutic target for ICC patients.
TL;DR: Entecavir and tenofovir achieved high biochemical and virological response in chronic hepatitis B and Renal function remained stable with both drugs, highlighting the importance of regular HCC surveillance even in patients withVirological suppression.
Abstract: Long-term antiviral therapy has resulted in viral suppression and biochemical response in chronic hepatitis B, although the risk of hepatocellular carcinoma has not been abolished. The Page-B score could be useful to estimate the probability of HCC. To analyze the effectiveness and safety of entecavir or tenofovir for more than 4 years and the usefulness of Page-B score in the real-world setting. Analysis of Caucasian chronic hepatitis B subjects treated with entecavir or tenofovir from the prospective, multicenter database CIBERHEP. A total of 611 patients were enrolled: 187 received entecavir and 424 tenofovir. Most were men, mean age 50 years, 32% cirrhotic and 16.5% HBeAg-positive. Mean follow-up was 55 (entecavir) and 49 (tenofovir) months. >90% achieved HBV DNA <69 IU/mL and biochemical normalization by months 12 and 36, respectively. Cumulative HBeAg loss and anti-HBe seroconversion were achieved by 33.7 and 23.8%. Four patients lost HBsAg; three HBeAg-positive. Renal function remained stable on long-term follow-up. Fourteen (2.29%) developed HCC during follow-up all of them with baseline Page-B ≥10. Nine were diagnosed within the first 5 years of therapy. This contrasts with the 27 estimated by Page-B, a difference that highlights the importance of regular HCC surveillance even in patients with virological suppression. Entecavir and tenofovir achieved high biochemical and virological response. Renal function remained stable with both drugs. A Page-B cut-off ≥10 selected all patients at risk of HCC development.