Gastrointestinal disturbances have been frequently, but not unanimously, reported in autism spectrum disorder (ASD) individuals. Thus, digestive symptoms, such as constipation, diarrhea, abdominal ...bloating, and pain have been reported to correlate to the various maladaptive behaviors in ASD children, such as irritability, social withdrawal, stereotypy, hyperactivity, and even language regression. In this context, the present study provides an overview on the prevalence of the gastrointestinal (GI) disorders in ASD and the correlation between these and ASD symptoms and comorbidities and subsequently discusses the metabolic and microbiome factors underlying the effects of GI disorders in ASD.
For our analysis of GI symptoms in children with ASD, we have searched peer-reviewed journals from 2005 to 2017 in PubMed databases that addressed the specificity of GI symptoms in ASD and included correlations of GI and ASD symptoms. The criteria for inclusion were clear quantitative mentioning of GI modifications, GI symptoms correlation with specific ASD symptoms or comorbidities, an appropriate methodology for defining ASD, and larger size samples. For this topic, only studies on human patients and original research were considered. A subsequent search in PubMed databases in journals from 2000 to 2017 we analyzed 13 articles on the mechanisms underlying the impact of GI dysfunctions in ASD, including gut microbial dysbiosis, immune reactivity, genetics, and altered neurotransmitters on the gut-brain axis.
In the 18 original research studies that we selected out of an initial 327 studies, despite the different methodology, a predominant 83% highlighted the increased prevalence of GI symptoms in ASD patients. Constipation was most frequently cited, appearing in 12 of the studies (80%), followed by diarrhea reports in eight studies (53%). The association between cognitive and behavioral deficits and GI disorders was suggested in certain groups of ASD individuals.
The evidence presented so far by numerous studies seems to indicate that GI dysfunctions are of particular relevance in ASD, underlined by various abnormalities along the nervous connections between the central nervous system and the gut, such as impaired parasympathetic activity and increased endocrine stress response. Sufficiently large size samples and standardized methodology are required for future studies to clarify the complex interactions between GI disturbances and ASD symptoms.
To perform a systematic review and meta-analysis on proton pump inhibitors (PPIs) therapy and the risk of
infection (CDI). METHODS We conducted a systematic search of MEDLINE/PubMed and seven other ...databases through January 1990 to March 2017 for published studies that evaluated the association between PPIs and CDI. Adult case-control and cohort studies providing information on the association between PPI therapy and the development of CDI were included. Pooled odds ratios (ORs) estimates with 95% confidence intervals (CIs) were calculated using the random effect. Heterogeneity was assessed by
test and Cochran's
statistic. Potential publication bias was evaluated
funnel plot, and quality of studies by the Newcastle-Otawa Quality Assessment Scale (NOS).
Fifty-six studies (40 case-control and 16 cohort) involving 356683 patients met the inclusion criteria and were analyzed. Both the overall pooled estimates and subgroup analyses showed increased risk for CDI despite substantial statistical heterogeneity among studies. Meta-analysis of all studies combined showed a significant association between PPI users and the risk of CDI (pooled OR = 1.99, CI: 1.73-2.30,
< 0.001) as compared with non-users. The association remained significant in subgroup analyses: by design-case-control (OR = 2.00, CI: 1.68-2.38,
< 0.0001), and cohort (OR = 1.98, CI: 1.51-2.59,
< 0.0001); adjusted (OR = 1.95, CI: 1.67-2.27,
< 0.0001) and unadjusted (OR = 2.02, CI: 1.41-2.91,
0.0001); unicenter (OR = 2.18, CI: 1.72-2.75,
0.0001) and multicenter (OR = 1.82, CI: 1.51-2.19, P < 0.0001); age ≥ 65 years (OR = 1.93, CI: 1.40-2.68,
0.0001) and < 65 years (OR = 2.06, CI: 1.11-3.81,
0.01). No significant differences were found in subgroup analyses (test for heterogeneity):
0.93 for case-control
cohort,
0.85 for adjusted
unadjusted,
0.24 for unicenter
multicenter,
0.86 for age ≥ 65 years and < 65 years. There was significant heterogeneity across studies (
= 85.4%,
0.001) as well as evidence of publication bias (funnel plot asymmetry test,
0.002).
This meta-analysis provides further evidence that PPI use is associated with an increased risk for development of CDI. Further high-quality, prospective studies are needed to assess whether this association is causal.
Inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), is a chronic inflammatory disorder characterized by alternating phases of clinical relapse and remission. ...The etiology of IBD remains largely unknown, although a combination of patient's immune response, genetics, microbiome, and environment plays an important role in disturbing intestinal homeostasis, leading to development and perpetuation of the inflammatory cascade in IBD. As chronic intestinal inflammation is associated with the formation of reactive oxygen and reactive nitrogen species (ROS and RNS), oxidative and nitrosative stress has been proposed as one of the major contributing factor in the IBD development. Substantial evidence suggests that IBD is associated with an imbalance between increased ROS and decreased antioxidant activity, which may explain, at least in part, many of the clinical pathophysiological features of both CD and UC patients. Hereby, we review the presently known oxidant and antioxidant mechanisms involved in IBD-specific events, the animal models used to determine these specific features, and also the antioxidant therapies proposed in IBD patients.
Although a considerable number of studies support a substantial increase in incidence, severity, and healthcare costs for Clostridium difficile infection(CDI) in inflammatory bowel disease(IBD), only ...few evaluate its impact on IBD outcome. Medline and several other electronic databases from January 1993 to October 2013 were searched in order to identify potentially relevant literature. Most of the studies showed that IBD patients with CDI present a greater proportion of worse outcomes than those without CDI. These patients have longer length of hospital stay, higher rates of colectomies, and increased mortality. Patients with ulcerative colitis are more susceptible to CDI and have more severe outcomes than those with Crohn’s disease. However, studies reported variable results in both short-and long-term outcomes. Contrasting results were also found between studies using nationwide data and those reporting from single-center, or between some NorthAmerican and European studies. An important limitation of all studies analyzed was their retrospective design. Due to contrasting data often provided by retrospective studies, further prospective multi-center studies are necessary to evaluate CDI impact on IBD outcome. Until then, a rapid diagnosis and adequate therapy of infection are of paramount importance to improve IBD patients’ outcome. The aim of this article is to provide up to date information regarding CDI impact on outcome in IBD patients.
Worldwide, the leading cause of chronic liver disease is represented by nonalcoholic fatty liver disease (NAFLD) which has now become a global epidemic of the 21st century, affecting 1 in 4 adults, ...and which appears to be associated with the steadily increasing rates of metabolic syndrome and its components (obesity, type 2 diabetes mellitus (T2DM), and dyslipidemia). NAFLD has been reported to be associated with extrahepatic manifestations such as cardiovascular disease, T2DM, chronic kidney disease, extrahepatic malignancies (e.g., colorectal cancer), endocrine diseases (e.g., hypothyroidism, polycystic ovarian syndrome, psoriasis, and osteoporosis), obstructive sleep apnea, and iron overload. The prevalence of NAFLD is very high, affecting 25–30% of the world population and encloses two steps: (1) nonalcoholic fatty liver (NAFL), which includes steatosis only, and (2) nonalcoholic steatohepatitis (NASH) defined by the presence of steatosis and inflammation with hepatocyte ballooning, with or without fibrosis which can progress to liver fibrosis, hepatocellular carcinoma, and liver transplantation. Current data define a more complex relationship between NAFLD and T2DM than was previously believed, underlining a bidirectional and mutual association between the two entities. This review aims to summarize the current literature regarding the incidence of T2DM among patients with NAFLD and also the prevalence of NAFLD in T2DM patients, highlighting the recent key studies. Clinicians should screen, diagnose, and treat T2DM in patients with NAFLD in order to avoid short- and long-term complications.
Liver biopsy （LB） has traditionally been considered the gold standard for pretreatment evaluation of liver fibro- sis in patients with chronic hepatitis C （CHC）. However, LB is an invasive procedure ...with several shortcomings （intra- and interobserver variability of histopathologi- cal interpretation, sampling errors, high cost） and the risk of rare but potentially life-threatening complica- tions. In addition, LB is poorly accepted by patients and it is not suitable for repeated evaluation. Further- more, the prevalence of CHC makes LB unrealistic to be performed in all patients with this disease who are candidates for antiviral therapy. The above-mentioned drawbacks of LB have led to the development of non- invasive methods for the assessment of liver fibrosis. Several noninvasive methods, ranging from serum marker assays to advanced imaging techniques, have proved to be excellent tools for the evaluation of liver fibrosis in patients with CHC, whereas the value of LB as a gold standard for staging fibrosis prior to antiviral therapy has become questionable for clinicians. De- spite significant resistance from those in favor of LB, noninvasive methods for pretreatment assessment of liver fibrosis in patients with CHC have become part of routine clinical practice. With protease inhibitors-based triple therapy already available and substantial im- provement in sustained virological response, the time has come to move forward to noninvasiveness, with no risks for the patient and, thus, no need for LB in the assessment of liver fibrosis in the decision making for antiviral therapy in CHC.
Nonalcoholic fatty liver disease (NAFLD) has emerged as the most frequent cause of liver disease worldwide, comprising a plethora of conditions, ranging from steatosis to end-stage liver disease. ...Cardiovascular disease (CVD) has been associated with NAFLD and CVD-related events represent the main cause of death in patients with NAFLD, surpassing liver-related mortality. This association is not surprising as NAFLD has been considered a part of the metabolic syndrome and has been related to numerous CVD risk factors, namely, insulin resistance, abdominal obesity, dyslipidemia, hyperuricemia, chronic kidney disease, and type 2 diabetes. Moreover, both NAFLD and CVD present similar pathophysiological mechanisms, such as increased visceral adiposity, altered lipid metabolism, increased oxidative stress, and systemic inflammation that could explain their association. Whether NAFLD increases the risk for CVD or these diagnostic entities represent distinct manifestations of the metabolic syndrome has not yet been clarified. This review focuses on the relation between NAFLD and the spectrum of CVD, considering the pathophysiological mechanisms, risk factors, current evidence, and future directions.
Nonalcoholic fatty liver disease (NAFLD) has a rising prevalence worldwide. Its potential for evolution towards liver cirrhosis and hepatocellular carcinoma, as well as associations with extrahepatic ...manifestations, represents a double burden for patients and physicians alike. Recently, there has been increasing evidence of the association between NAFLD and a number of endocrinopathies, such as hypothyroidism, polycystic ovarian syndrome (PCOS), hypopituitarism, growth hormone deficiency (GHD), hypogonadism, and hypercortisolism. Definite correlations are supported by clear evidence so far, but further studies are needed in order to completely clarify the pathogenic mechanisms and, especially, to identify therapeutic implications. In this review, we present the main relationships between NAFLD and endocrinopathies, emphasizing the reciprocal causality, evolutive interconnections, and current clinical scenarios of presentations of which the clinicians should be aware.
: Ulcerative colitis (UC) and Crohn's disease (CD) are idiopathic inflammatory bowel diseases (IBDs) without a unique, gold standard diagnostic test. UC and Crohn's colitis are impossible to ...distinguish in approximately 10% of cases. The term IBD type unclassified (IBD-U) is recommended for cases of chronic colitis showing overlapping endoscopic, radiological, and biopsy histological features between UC and CD, while indetermined colitis is reserved for colectomy specimens. Our aim was to assess the role of small-bowel capsule endoscopy (SBCE) in the diagnostic work-up of IBD-U.
: We retrospectively studied the cases of IBD-U explored by SBCE in a tertiary referral gastroenterology center. Patients were investigated using SBCE after contraindications were excluded. Diagnostic criteria for small bowel CD consisted in more than three ulcerations, irregular ulcers, or stenosis, and the Lewis score was used for the quantification of inflammation. The immediate impact of reclassification and outcome data was recorded over a follow-up period of more than one year.
: Twenty-eight patients with IBD-U were examined using SBCE. Nine patients had small bowel lesions that met the diagnostic criteria for CD, resulting in a reclassification rate of 32.1%. In five of these cases, the treatment was subsequently changed. In the remaining nineteen examinations, no significant findings were observed. There were no complications associated with SBCE. Median follow-up time was 32.5 months (range 12-60). During follow-up, twelve patients were classified as having UC, and seven remained as having an unclassified type; one case of colectomy, for medically refractory UC, was recorded.
: SBCE is a useful safe tool in the work-up of IBD-U, allowing reclassification in about one third of cases, with subsequent treatment modifications. SBCE may provide a definite diagnosis, enhance the comprehension of the disease's progression, and optimize the short- and long-term management strategy.
Summary Background We did a phase 3 study in previous non-responders with chronic hepatitis C virus (HCV) genotype 1 infection and compensated liver disease that related to the standard of care for ...these patients at the time this study was initiated. We investigated whether simeprevir is non-inferior in terms of efficacy to telaprevir, each in combination with peginterferon alfa-2a and ribavirin. Methods We did this randomised, double-blind, phase 3 trial at 169 investigational sites in 24 countries. We enrolled adults (≥18 years) with chronic HCV genotype 1 infection, compensated liver disease, and plasma HCV RNA higher than 10 000 IU/mL who were null or partial responders during at least one previous course of peginterferon alfa-2a and ribavirin treatment. We randomly assigned (1:1) patients (stratified by HCV genotype 1 subtype 1a plus other/1b and previous treatment response partial or null) to receive simeprevir (150 mg once a day) plus telaprevir placebo (three times a day 7–9 h apart) or telaprevir (750 mg three times a day) plus simeprevir placebo (once a day) in combination with peginterferon alfa-2a and ribavirin for 12 weeks followed by 36 weeks of peginterferon alfa-2a and ribavirin alone. The primary efficacy endpoint was sustained virological response 12 weeks after end of treatment (SVR12) in the intention-to-treat and the per-protocol population. We compared groups with the Cochran-Mantel-Haenszel test. We established a non-inferiority margin of 12%. Adverse events were reported descriptively. This trial is registered with ClinicalTrials.gov , number NCT01485991. Findings Patient screening began on Jan 19, 2012, and the last visit was on April 7, 2014. We included 763 patients (472 previous null responders 62%). Simeprevir and peginterferon alfa-2a and ribavirin was non-inferior to telaprevir and peginterferon alfa-2a and ribavirin for SVR12 (54% 203/379 vs 55% 210/384; difference −1·1%, 95% CI −7·8 to 5·5; p=0·0007). SVR12 was achieved in 70% (101/145) versus 68% (100/146) of previous partial responders and 44% (102/234) versus 46% (110/238) of previous null responders with simeprevir and peginterferon alfa-2a and ribavirin and telaprevir and peginterferon alfa-2a and ribavirin treatment, respectively. We recorded differences between treatment groups in simeprevir or telaprevir-related adverse events (69% 261/379 in the simeprevir group vs 86% 330/384 in the telaprevir group), serious adverse events (2% 8/379 vs 9% 33/384), and adverse events leading to simeprevir or telaprevir discontinuation (2% 7/379 vs 8% 32/384). Interpretation Simeprevir once a day with peginterferon alfa-2a and ribavirin was well tolerated in HCV genotype 1-infected previous non-responders and was non-inferior to telaprevir, thus providing an alternative treatment in areas of the world where all-oral HCV regimens are not available or accessible. Funding Janssen.
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