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1.
Int J Hepatol ; 2019: 4793096, 2019.
Article in English | MEDLINE | ID: mdl-31355004

ABSTRACT

BACKGROUND AND STUDY AIMS: Patients undergoing therapeutic endoscopic retrograde cholangiography (ERC) may require different amounts of sedative agents depending on demographic characteristics, indication of ERC, and/or endoscopic intervention. PATIENTS AND METHODS: We retrospectively analyzed all patients undergoing therapeutic ERC from 2008 - 2014 who received deep sedation with propofol ± midazolam. RESULTS: A total of 2448 ERC procedures were performed in 781 patients. The cumulative per procedure propofol dose in the different groups was as follows: PSC 479 mg (±256), bile duct stones 356 mg (±187), benign stenosis/cholestasis 395 mg (±228), malignant stenosis 401 mg (±283), and postliver transplant complications 391 mg (±223) (p < 0.05). Multivariable analysis showed that dilatation therapy (p = 0.001), age (p = 0.001), duration of the intervention (p = 0.001), BMI (p = 0.001), gender (p = 0.001), platelet count (p = 0.003), and bilirubin (p = 0.043) influence independently the propofol consumption. CONCLUSIONS: Demographic characteristics and endoscopic interventions have a distinct influence on the amount of sedation required for therapeutic ERC. Although the sedation-associated complication rate is low optimization of sedative regimens is a prime goal to further reduce adverse events of therapeutic ERC.

2.
Eur J Gastroenterol Hepatol ; 31(1): 99-108, 2019 01.
Article in English | MEDLINE | ID: mdl-30212402

ABSTRACT

BACKGROUND: The value of therapeutic drug monitoring during azathioprine (AZA) therapy with respect to clinical outcomes has been convincingly demonstrated in recent meta-analyses. However, the association between AZA metabolites and the mucosal state in inflammatory bowel disease is largely unclear. AIMS: We investigated the association between AZA's active metabolite 6-thioguanine nucleotides (6-TGN) and fecal calprotectin (FC) as a well-validated surrogate marker of mucosal inflammation in patients with Crohn's disease (CD) on AZA monotherapy. PATIENTS AND METHODS: Of 443 6-TGN measurements, 140 values from 88 patients with CD on AZA monotherapy visiting the inflammatory bowel disease outpatient clinic between 2009 and 2016 were retrospectively analyzed. In a subcohort with serial 6-TGN measurements, longitudinal FC measurements in patients with versus without intervention (dose increase, allopurinol, and education) were assessed. RESULTS: In patients with 6-TGN concentrations within a predefined range (250-450 pmol/8×10 red blood cells), FC was significantly lower (median: 119.5 vs. 327.2 mg/kg, P=0.003), and hemoglobin as well as serum protein concentrations were significantly higher than in patients with 6-TGN outside of this range. C-reactive protein and transferrin saturation were not different. In the longitudinal cohort, 6-TGN increased in the intervention group, but only a minority reached the defined range; no significant change in FC was observed. CONCLUSION: This study is the first to show that in patients with CD receiving AZA monotherapy, 6-TGN concentrations within a defined range (250-450 pmol/8×10 red blood cells) are associated with significantly lower FC. A treat-to-target concept directed by 6-TGN to reach mucosal healing may thus be a promising approach (DRKS00013246).


Subject(s)
Anti-Inflammatory Agents/therapeutic use , Azathioprine/therapeutic use , Crohn Disease/drug therapy , Drug Monitoring/methods , Erythrocytes/metabolism , Feces/chemistry , Gastrointestinal Agents/therapeutic use , Guanine Nucleotides/blood , Intestinal Mucosa/drug effects , Leukocyte L1 Antigen Complex/metabolism , Thionucleotides/blood , Adult , Anti-Inflammatory Agents/blood , Azathioprine/blood , Biomarkers/blood , Crohn Disease/blood , Crohn Disease/diagnosis , Cross-Sectional Studies , Female , Gastrointestinal Agents/blood , Humans , Intestinal Mucosa/metabolism , Intestinal Mucosa/pathology , Longitudinal Studies , Male , Middle Aged , Predictive Value of Tests , Retrospective Studies , Time Factors , Treatment Outcome , Wound Healing/drug effects
3.
Endosc Int Open ; 5(4): E315-E320, 2017 Apr.
Article in English | MEDLINE | ID: mdl-28393105

ABSTRACT

Background and study aims Patients with primary sclerosing cholangitis (PSC) require repeated endoscopic retrograde cholangiography (ERC). Our aim was to evaluate whether patients with PSC require higher doses of sedation during ERC. Patients and methods We retrospectively analyzed all patients undergoing ERC from 2006 to 2013 who received conscious sedation with propofol and midazolam. The duration of the intervention and a potential progression of propofol consumption or intervention time by visit number were analyzed. Univariable and multivariable analyses were performed to identify independent factors which influence propofol consumption. Results A total of 2962 ERC procedures were performed in 1211 patients. Patients with PSC (n = 157) underwent 461 ERC procedures whereas patients without PSC (n = 1054) had 2501 ERC examinations. The total median propofol dose was 450 mg (290 - 630 mg) for patients with PSC and 300 mg (200 - 450 mg) for the non-PSC group (P < 0.05). The propofol consumption in patients with PSC was increased by a factor of 1.24 (P = 0.0071) independent of intervention time. Younger age (< 60.8 years) and duration of the intervention were associated with a higher need for sedation by factors of 1.21 and 1.71, respectively (P < 0.0001). The robustness of the results was tested in a sensitivity analysis which confirmed the results (P < 0.0001). Conclusions Patients with PSC may require higher doses of sedation for ERC compared to other patient groups independent of age and duration of ERC. The higher dosage of sedation has to be taken into account when using ERC to treat a patient with PSC.

4.
BMC Neurosci ; 13: 141, 2012 Nov 08.
Article in English | MEDLINE | ID: mdl-23134591

ABSTRACT

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder, caused by progressive loss of motor neurons. Changes are widespread in the subcortical white matter in ALS. Diffusion tensor imaging (DTI) detects pathological changes in white matter fibres in vivo, based on alterations in the degree (diffusivity, ADC) and directedness (fractional anisotropy, FA) of proton movement. METHODS: 24 patients with ALS and 24 age-matched controls received 1.5T DTI. FA and ADC were analyzed using statistical parametric mapping. In 15 of the 24 ALS patients, a second DTI was obtained after 6 months. RESULTS: Decreased FA in the corticospinal tract (CST) and frontal areas confirm existing results. With a direct comparison of baseline and follow-up dataset, the progression of upper motor neuron degeneration, reflected in FA decrease, could be captured along the CST and in frontal areas. The involvement of cerebellum in the pathology of ALS, as suspected from functional MRI studies, could be confirmed by a reduced FA (culmen, declive). These structural changes correlated well with disease duration, ALSFRS-R, and physical and executive functions. CONCLUSION: DTI detects changes that are regarded as prominent features of ALS and thus, shows promise in its function as a biomarker. Using the technique herein, we could demonstrate DTI changes at follow-up which correlated well with clinical progression.


Subject(s)
Amyotrophic Lateral Sclerosis/pathology , Amyotrophic Lateral Sclerosis/physiopathology , Brain Mapping , Cerebral Cortex/pathology , Diffusion Tensor Imaging , Pyramidal Tracts/pathology , Adult , Aged , Analysis of Variance , Case-Control Studies , Female , Humans , Longitudinal Studies , Male , Mental Status Schedule , Middle Aged , Neuropsychological Tests , Severity of Illness Index , Statistics as Topic
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