Relationship of faecal calprotectin and long-term outcomes in Finnish patients with Crohn's disease: retrospective multi-centre chart review study.

Background and Aims: A retrospective non-interventional, multi-centre patient chart review study was conducted to investigate the association of faecal calprotectin (FC) 1 year (±2 months) after biological therapy initiation with composite event-free survival (CEFS) consisting of surgical procedures, corticosteroid initiation, treatment failure or dose increase in patients with Crohn's disease (CD). In addition, the correlations of FC and other tests of disease activity were assessed.Materials and methods: Data on Finnish CD patients initiating a biological therapy between 2010 and 2016, were collected. The association of FC and CEFS was analysed with Kaplan-Meier and Cox proportional hazard modelling. The correlations were tested with Pearson's test.Results: Biological therapy was initiated in 186 patients, of which 87 (46.8%) had FC results available at 1 year and 80 had follow-up exceeding 14 months. The characteristics of patients with and without FC results were similar. Patients with elevated FC (>250 µg/g) had a significantly increased risk of experiencing composite event (HR 3.4, 95% CI: 1.3-8.9; p = .013) when compared to patients with normal FC (FC ≤ 100). No such risk was observed in patients with intermediately increased FC level (100 µg/g < FC ≤ 250 µg/g) (HR 2.2 (95% CI: 0.8-6.2; p = .120). FC value had significant positive correlation with CRP, HBI and leukocyte values when measured at similar timepoints.Conclusions: Elevated level of FC approximately 1 year after the initiation of biological therapy was associated with an increased risk of either surgical procedures, corticosteroid initiation, treatment failure or dose increase (i.e. composite outcome) in patients with CD.

Deep breathing improves blunted baroreflex sensitivity even after 30 years of type 1 diabetes.

AIMS/HYPOTHESES: Cardiovascular autonomic neuropathy is associated with increased morbidity in patients with type 1 diabetes. Although it is conventionally considered to be an organic, irreversible disorder, we previously demonstrated in patients with short-duration type 1 diabetes that reduced baroreflex sensitivity (BRS) could be corrected by slow, deep breathing, indicating a functional component to the disorder. We have now tested whether autonomic abnormalities in long-term diabetes progress to a stage that cannot be modified by functional manoeuvres, indicating a switch towards predominantly organic dysfunction. METHODS: We studied 117 patients with a short duration (8.9 ± 0.1 years) and 37 patients with a long duration (33.7 ± 0.5 years) of type 1 diabetes, 73 healthy controls and 12 heart-transplanted participants (surgical heart denervation). An autonomic score was calculated from autonomic function tests. Spectral analysis of heart rate and blood pressure variability, and BRS, were obtained from recordings during normal (15 breaths per min) and slow, deep (six breaths per min) controlled breathing. RESULTS: BRS was reduced in all patients, but more in patients with a long duration of diabetes or with increasing autonomic involvement, although the effect of duration disappeared after adjustment for age. Slow breathing increased the BRS to the level of the control participants at a normal rate of breathing (15 per min) in all patients except those with an abnormal autonomic score. CONCLUSIONS/INTERPRETATION: Patients with type 1 diabetes have a blunted BRS that in the majority of patients can be restored by slow breathing, irrespective of disease duration. Even after a long duration of diabetes, the abnormal BRS is at least in part of functional origin.

Early autonomic dysfunction in type 1 diabetes: a reversible disorder?

AIMS/HYPOTHESIS: Cardiac autonomic neuropathy is associated with increased morbidity and mortality rates in patients with type 1 diabetes. The prevalence of early autonomic abnormalities is relatively high compared with the frequency of manifest clinical abnormalities. Thus, early autonomic dysfunction could to some extent be functional and might lead to an organic disease in a subgroup of patients only. If this is true, manoeuvres such as slow deep-breathing, which can improve baroreflex sensitivity (BRS) in normal but not in denervated hearts, could also modify autonomic modulation in patients with type 1 diabetes, despite autonomic dysfunction. METHODS: We compared 116 type 1 diabetic patients with 36 matched healthy control participants and 12 heart-transplanted participants with surgically denervated hearts. Autonomic function tests and spectral analysis of heart rate and blood pressure variability were performed. BRS was estimated by four methods during controlled (15 breaths per minute) and slow deep-breathing (six breaths per minute), and in supine and standing positions. RESULTS: Conventional autonomic function tests were normal, but resting spectral variables and BRS were reduced during normal controlled breathing in patients with type 1 diabetes. However, slow deep-breathing improved BRS in patients with type 1 diabetes, but not in patients with surgically denervated hearts. Standing induced similar reductions in BRS in diabetic and control participants. CONCLUSIONS/INTERPRETATION: Although we found signs of increased sympathetic activity in patients with type 1 diabetes, we also observed a near normalisation of BRS with a simple functional test, indicating that early autonomic derangements are to a large extent functional and potentially correctable by appropriate interventions.