Systematic review of nutrition screening and assessment in inflammatory bowel disease

BACKGROUND Malnutrition is prevalent in inflammatory bowel disease (IBD). Multiple nutrition screening (NST) and assessment tools (NAT) have been developed for general populations, but the evidence in patients with IBD remains unclear. AIM To systematically review the prevalence of abnormalities on NSTs and NATs, whether NSTs are associated with NATs, and whether they predict clinical outcomes in patients with IBD. METHODS Comprehensive searches performed in Medline, CINAHL Plus and PubMed. Included: English language studies correlating NSTs with NATs or NSTs/NATs with clinical outcomes in IBD. Excluded: Review articles/case studies;use of body mass index/laboratory values as sole NST/NAT;age<16. RESULTS Of 16 studies and 1618 patients were included, 72% Crohn’s disease and 28% ulcerative colitis. Four NSTs (the Malnutrition Universal Screening Tool, Malnutrition Inflammation Risk Tool (MIRT), Saskatchewan Inflammatory Bowel Disease Nutrition Risk Tool (SaskIBD-NRT) and Nutrition Risk Screening 2002 (NRS-2002) were significantly associated with nutritional assessment measures of sarcopenia and the Subjective Global Assessment (SGA). Three NSTs (MIRT, NRS-2002 and Nutritional Risk Index) were associated with clinical outcomes including hospitalizations, need for surgery, disease flares, and length of stay (LOS). Sarcopenia was the most commonly evaluated NAT associated with outcomes including the need for surgery and post-operative complications. The SGA was not associated with clinical outcomes aside from LOS. CONCLUSION There is limited evidence correlating NSTs, NATs and clinical outcomes in IBD. Although studies support the association of NSTs/NATs with relevant outcomes, the heterogeneity calls for further studies before an optimal tool can be recommended. The NRS-2002, measures of sarcopenia and developments of novel NSTs/NATs, such as the MIRT, represent key, clinically-relevant areas for future exploration.     

Report from the American Society of Transplantation on frailty in solid organ transplantation

A consensus conference on frailty in kidney, liver, heart, and lung transplantation sponsored by the American Society of Transplantation (AST) and endorsed by the American Society of Nephrology (ASN), the American Society of Transplant Surgeons (ASTS), and the Canadian Society of Transplantation (CST) took place on February 11, 2018 in Phoenix, Arizona. Input from the transplant community through scheduled conference calls enabled wide discussion of current concepts in frailty, exploration of best practices for frailty risk assessment of transplant candidates and for management after transplant, and development of ideas for future research. A current understanding of frailty was compiled by each of the solid organ groups and is presented in this paper. Frailty is a common entity in patients with end‐stage organ disease who are awaiting organ transplantation, and affects mortality on the waitlist and in the posttransplant period. The optimal methods by which frailty should be measured in each organ group are yet to be determined, but studies are underway. Interventions to reverse frailty vary among organ groups and appear promising. This conference achieved its intent to highlight the importance of frailty in organ transplantation and to plant the seeds for further discussion and research in this field.     

Effects of ciclesonide and fluticasone propionate on allergen-induced airway inflammation and remodeling features

BACKGROUND: Several topical corticosteroids are available as anti-inflammatory treatment for asthma. Their comparative effects on allergic inflammation and airway remodeling are unclear. OBJECTIVE: We compared the effects of ciclesonide with those of fluticasone propionate in a Brown Norway rat model of chronic allergic asthma. METHODS: Rats sensitized and exposed to ovalbumin (OVA) were treated with dry powder vehicle, ciclesonide, or fluticasone (0.01, 0.03, and 0.1 mg/kg administered intratracheally) 24 hours and 1 hour before each of 6 OVA exposures. In a second protocol we administered 0.1 mg/kg ciclesonide or fluticasone only after the third OVA exposure. RESULTS: Ciclesonide at all doses inhibited the allergen-induced increase in airway eosinophils and T cells, reduced goblet cell hyperplasia, and decreased 5-bromo-2'-deoxyuridine-immunoreactive airway smooth muscle (ASM) and epithelial cells. At 0.03 and 0.1 mg/kg ciclesonide, bronchial hyperresponsiveness (BHR) was also inhibited. Fluticasone did not attenuate allergen-induced BHR, despite inhibiting airway eosinophils and T cells, goblet cell hyperplasia, and 5-bromo-2'-deoxyuridine-immunoreactive ASM and epithelial cells. Fluticasone (0.1 mg/kg) caused a significant reduction in body weight (9%) compared with ciclesonide (0.1 mg/kg). Ciclesonide did not change plasma corticosterone levels, whereas fluticasone (0.1 mg/kg) reduced them. In the second protocol both fluticasone and ciclesonide inhibited BHR, bronchial inflammation, goblet cell hyperplasia, and ASM proliferation. CONCLUSION: Ciclesonide potently inhibited chronic allergic inflammation, remodeling, and BHR without having an effect on body weight and the hypothalamic-pituitary-adrenal axis. Fluticasone prevented airway inflammation but not BHR, but both fluticasone and ciclesonide are effective at reversal of BHR, inflammation, and remodeling features.     

Importance of p38 mitogen-activated protein kinase pathway in allergic airway remodelling and bronchial hyperresponsiveness

p38 mitogen-activated protein kinase (MAPK) plays an important role in the activation of inflammatory cells and in the proliferation of airway structural cells. We investigated the role of p38 MAPK by using a selective inhibitor of p38 alpha and beta isoforms, SD282, in a chronic model of 15 ovalbumin exposures in sensitised mice using two doses (30 and 90 mg/kg). Allergen exposure induced bronchial hyperresponsiveness to methacholine as measured by the concentration of methacholine needed to increase pulmonary resistance by 200% (PC200), eosinophilia in bronchoalveolar lavage fluid and increase in airway smooth muscle area and goblet cell hyperplasia. In addition, p38 MAPK activity as measured by phosphorylated p38 expression on Western blots was increased after allergen challenge, which was suppressed by SD282 at both doses. SD282 inhibited bronchial hyperresponsiveness, but had no effect on eosinophils in bronchoalveolar lavage fluid. It also reduced airway smooth muscle and goblet cell hyperplasia, but had no effect on serum immunoglobulin E. p38 MAPK is involved in the pathogenesis of bronchial hyperresponsiveness but not in eosinophilic inflammation or the allergic response; however, remodelling features such as airway smooth muscle or goblet cell hyperplasia are regulated through p38 MAPK. Furthermore, bronchial hyperresponsiveness induced by chronic allergen exposure may be related to the development of airway wall remodelling.     

International Classification of Diseases Codes are Useful in Identifying Cirrhosis in Administrative Databases

Digestive Diseases and Sciences - Health administrative databases are essential to define patient populations, make socioeconomic predictions, and facilitate medical research and healthcare...     

Third-generation cephalosporin-resistant spontaneous bacterial peritonitis: A single-centre experience and summary of existing studies

BACKGROUND:

Spontaneous bacterial peritonitis (SBP) is the most prevalent bacterial infection in patients with cirrhosis. Although studies from Europe have reported significant rates of resistance to third-generation cephalosporins, there are limited SBP-specific data from centres in North America.

OBJECTIVE:

To evaluate the prevalence of, predictors for and clinical impact of third-generation cephalosporin-resistant SBP at a Canadian tertiary care centre, and to summarize the data in the context of the existing literature.

METHODS:

SBP patients treated with both antibiotics and albumin therapy at a Canadian tertiary care hospital between 2003 and 2011 were retrospectively identified. Multivariate logistic regression was used to determine independent predictors of third-generation cephalosporin resistance and mortality.

RESULTS:

In 192 patients, 25% of infections were nosocomial. Forty per cent (77 of 192) of infections were culture positive; of these, 19% (15 of 77) were resistant to third-generation cephalosporins. The prevalence of cephalosporin resistance was 8% with community-acquired infections, 17% with health care-associated infections and 41% with nosocomial acquisition. Nosocomial acquisition of infection was the only predictor of resistance to third-generation cephalosporins (OR 4.0 [95% CI 1.04 to 15.2]). Thirty-day mortality censored for liver transplantation was 27% (50 of 184). In the 77 culture-positive patients, resistance to third-generation cephalosporins (OR 5.3 [1.3 to 22]) and the Model for End-stage Live Disease score (OR 1.14 [1.04 to 1.24]) were independent predictors of 30-day mortality.

CONCLUSIONS:

Third-generation cephalosporin-resistant SBP is a common diagnosis and has an effect on clinical outcomes. In an attempt to reduce the mortality associated with resistance to empirical therapy, high-risk subgroups should receive broader empirical antibiotic coverage.     

Low subcutaneous adiposity associates with higher mortality in female patients with cirrhosis

1. Download high-res image (211KB)
2. Download full-size image

     

Frailty in Patients With Cirrhosis

Purpose of review

This review gives an overview of the evolving concept of physical frailty in patients with cirrhosis. As well as summarizing the available metrics that have been used to diagnose it, this review also examines the major recent trials that have investigated frailty in patients with cirrhosis. The complex relationship between sarcopenia and frailty is explored, and strategies to optimize frailty, such as including pharmacological and non-pharmacological therapies, are discussed.

Recent findings

Though there is heterogeneity between studies on how physical frailty in cirrhosis has been assessed, it is nonetheless becoming increasingly apparent that frailty in cirrhosis contributes to poor outcomes. A growing body of evidence strongly supports that frailty, as an entity distinct from comorbidity or measurable by laboratory-based liver disease severity, contributes to pre-transplant mortality and unplanned hospital admissions. If taken into account, frailty may improve pre-transplant mortality risk prediction.

Summary

Physical frailty in cirrhosis may be objectively assessed by a number of validated metrics though at present, we lack a uniform consensus on the most appropriate tool. Early identification of frailty may allow optimization of the patient with the potential to avoiding adverse outcomes. Further studies are awaited validating and exploring optimal approaches to diagnosing and reversing frailty.

     

The spectrum of neurological manifestations and genotype–phenotype correlation in Indian children with Gaucher disease

Gaucher disease (GD), one of the most frequent autosomal recessive lysosomal storage disorders, occurs due to bi-allelic pathogenic variants in the GBA1. Worldwide, the c.1448T>C (L483P) homozygous pathogenic variant is reported to be associated with neurological GD phenotype. Clinical distinction between GD1 and GD3 may be challenging due to subtle neurological features. Objective methods to evaluate neurological signs and saccades may help in early diagnosis. This study was conducted to assess the neurological phenotype, and its severity using a modified severity scoring tool (mSST), and the genotype–phenotype correlation. A total of 45 children aged 2 years 6 months to 15 years with a confirmed enzymatic and molecular diagnosis of GD with or without therapy were recruited. mSST tool was used to assess the severity of the neurological phenotype. A digital eye movement tracker (View Point Tracker) was used to assess eye movements. Clinical and genetic findings were analyzed. Out of 45 patients, 39 (86.7%) had at least one neurological phenotype detected using the mSST tool, with impairment of cognitive function (68.8%, 31/45) being the commonest feature. Thirty-two of 45 (71%) were assessed for saccadic eye movements using the eye tracker. Of these, 62.5% (20/32) had absent saccades. Four children (8.9%, 4/32) without clinical oculomotor apraxia had absent saccades on the viewpoint eye tracker. Overall, 77.7% (35/45), had homozygosity for c.1448T>C in GBA1 of which 91.4% (32/35) had neurological manifestations. Other alleles associated with neurological phenotype included c.1603C>T(p.R535C), c.1184C>T (p.S395F), c.115+1G>A (g.4234G>A), c.260G>A (p.R87Q) and c.1352A>G (p.Y451C). To conclude, in India, the c.1448T>C pathogenic variant in GBA1 is the commonest  and is associated with neurological phenotype of GD. Therefore, every patient of GD should be assessed using the mSST scoring tool for an early pick up of neurological features. The routine use of a viewpoint eye tracker in children with GD would be useful for early recognition of saccadic abnormalities.