Microsomal triglyceride transfer protein polymorphism (−493G/T) is associated with hepatic steatosis in patients with chronic hepatitis C

Background: Hepatic steatosis may promote progression of chronic hepatitis C (CHC). Microsomal triglyceride transfer protein (MTP) is required for assembly and secretion of ApoB lipoprotein and is implicated in hepatitis C virus (HCV)‐related steatosis. The MTP ?493G/T polymorphism may promote liver fat accumulation, but its role in HCV‐related steatosis is still unclear. Methods: Two hundred ninety‐eight CHC patients were studied and genotyped for MTP ?493G/T variants. Hepatic MTP mRNA expression and activity were determined in a subgroup. Results: Patients with grades 2/3 steatosis were older, had a higher body mass index (BMI), more advanced fibrosis and lower MTP mRNA expression and carried more often HCV genotype 3 and the MTP T allele. Age, BMI, HCV‐3 and MTP T allele [odds ratio (OR) 2.05; 95% confidence interval (CI) 1.2–3.53; P=0.009] were independent risk factors for steatosis grades 2/3, and in HCV genotype non‐3 patients, the MTP T allele was the strongest predictor for steatosis grade 2/3 (OR 2.17; 95% CI 1.22–3.86; P=0.008). Moreover, TT carriers had higher high‐density lipoprotein (65.6±14.6 vs 56.1±16.2 mg/dl; P=0.003) and apolipoprotein AI (1.80±0.3 vs 1.60±0.3 g/L; P=0.005) levels than G allele carriers. Conclusions: Chronic hepatitis C patients with the MTP ?493T allele reveal higher grades of steatosis, indicating a relevant contribution to liver fat accumulation, particularly in HCV non‐3 patients.     

How fast up the ladder? Factors associated with immunosuppressive or anti-TNF therapies in IBD patients at early stages: results from a population-based cohort

Background

With the introduction of anti-TNF therapies in the treatment of IBD, the therapeutic strategies have changed to an accelerated step-up care to avoid long-term complications. Little is known about the implementation of these strategies into daily care. We aimed to evaluate this question and to identify factors associated with the early use of immunosuppressants or anti-TNF therapies in a population-based IBD cohort.

Methods

Patients with an IBD diagnosed between January 2004 and December 2008 were included. Medical therapies were evaluated at first diagnosis and during a 5-year follow-up. Risk factors associated with the initiation of an immunosuppressive therapy were assessed.

Results

Two hundred and forty-one patients were evaluated (145 Crohn’s disease (CD), 96 ulcerative colitis (UC)). An immunosuppressive or anti-TNF therapy was started in 83 CD (57.2 %) and 40 UC (43 %) patients (p?=?0.033, relative risks (RR) 1.77; 95 % confidence interval (CI) 1.05–3.0). After 5 years, 38.8 % CD patients on immunosuppressive therapy were treated with anti-TNF therapies. The use of corticosteroids at first diagnosis, disease localization and surgery were independent predictors for an immunosuppressive or anti-TNF therapy in CD. In UC, the extension of disease was associated with immunosuppressive therapies. The use of steroids and localization in CD patients and an extended disease in UC patients affected the time until an immunosuppressive therapy was started.

Conclusion

We found a high proportion of patients using an immunosuppressive therapy during the early course. Therefore, the accelerated step-up strategy seems to be successfully implemented in the daily care of IBD patients. We were able to identify several factors associated with an immunosuppressive or anti-TNF therapy in CD and UC.     

Comparing the accuracy of transcutaneous sensor and 90-day implantable glucose sensor

Background and aimsContinuous glucose monitoring improves glycemic control in diabetes. This study compared the accuracy of the Dexcom G5 Mobile (Dexcom, San Diego, CA) transcutaneous sensor (DG5) and the first version of Eversense (Senseonics,Inc., Germantown, MD) implantable sensor (EVS).Methods and resultsSubjects with type 1 diabetes (T1D) and using EVS wore simultaneously DG5 for seven days. At day 3, patients were admitted to a clinical research center (CRC) to receive breakfast with delayed and increased insulin bolus to induce glucose excursions. At CRC, venous glucose was monitored every 15 min (or 5 min during hypoglycemia) for 6 h by YSI 2300 STAT PLUS? glucose and lactate analyzer. At home patients were requested to perform 4 fingerstick glucose measurements per day.Eleven patients (9 males, age 47.4 ± 11.3 years, M±SD) were enrolled. During home-stay the median [25th-75th percentile] absolute relative difference (ARD) over all CGM-fingerstick matched-pairs was 11.64% [5.38–20.65]% for the DG5 and 10.75% [5.15–19.74]% for the EVS (p-value = 0.58). At CRC, considering all the CGM-YSI matched-pairs, the DG5 showed overall smaller median ARD than EVS, 7.91% [4.14–14.30]% vs 11.4% [5.04–18.54]% (p-value<0.001). Considering accuracy during blood glucose swings, DG5 performed better than EVS when glucose rate-of-change was ?0.5 to ?1.5 mg/dL/min, with median ARD of 7.34% [3.71–12.76]% vs 13.59% [4.53–20.78]% (p-value<0.001), and for rate-of-change < -1.5 mg/dl/min, with median ARD of 5.23% [2.09–15.29]% vs 12.73% [4.14–20.82]% (p-value = 0.02).ConclusionsDG5 was more accurate than EVS at CRC, especially when glucose decreased. No differences were found at home.     

Assessing the demand for psychological care in chronic diseases: development and validation of a questionnaire based on the example of inflammatory bowel disease

BACKGROUND: This study was designed to develop and validate the ADAPT (Assessment of the Demand for Additional Psychological Treatment), a questionnaire assessing the demand for disease-oriented counseling (DOC), integrated psychosomatic care (IPC), and psychotherapy (PT) in chronically ill patients on the example of inflammatory bowel diseases (IBDs). METHODS: After its development, the ADAPT was distributed to 39 IBD patients along with the Hospital Anxiety and Depression scale (HAD), the Rating Form of IBD Patient Concerns (RFIPC), and a questionnaire on social support (SOZU-K22). For construct validity, 19 hypotheses were made on how DOC, IPC, and PT should correlate with HAD, RFIPC, SOZU-K22, and disease-related variables. To analyze interindividual responsiveness, patients were classified according to their bio-psycho-social state, and DOC, IPC, and PT scores were compared between these classes. The test-retest method with a 4-week time lapse was used to analyze reliability and intraindividual responsiveness. DOC, IPC, and PT scores between baseline and follow-up were compared separately for patients classified as "stable" or "changed" according to changes in HAD and disease activity. RESULTS: Observed correlations were largely in agreement with the 19 hypotheses. DOC, IPC, and PT achieved significantly different scores between different patients. After 4 weeks, DOC, IPC, and PT revealed stable scores in patients with "stable" HAD and revealed significantly different scores in patients with "changed" HAD. Changed disease activity was not associated with significant changes of the ADAPT. CONCLUSIONS: The ADAPT is the first questionnaire to assess subjective demand for additional psychological care in chronically ill patients. The first application of the ADAPT to 39 IBD patients suggests its validity, reliability, and responsiveness.     

High levels of circulating CXC chemokine ligand 10 are associated with chronic autoimmune thyroiditis and hypothyroidism

CXC chemokine ligand 10 (CXCL10), an interferon-gamma-inducible chemokine associated with Th1-mediated immune responses, has been proposed as a marker of inflammation in autoimmune diseases. We measured serum CXCL10 concentrations in 223 consecutive patients with newly diagnosed autoimmune thyroiditis (AT), 97 euthyroid controls, and 29 patients with nontoxic multinodular goiter and related this parameter to the clinical phenotype. The three groups were similar in gender distribution and age; among the AT patients, 24% had subclinical hypothyroidism. Serum CXCL10 level was significantly higher in AT patients (157 +/- 139 pg/ml) than in controls (79 +/- 38) or patients with multinodular goiter (90 +/- 32; P < 0.0001). Among patients with AT, CXCL10 levels were significantly higher in those with a hypoechoic ultrasonographic pattern and hypothyroidism. In a multiple linear regression model including age, thyroid volume, hypoechogenicity, hypervascularity, TSH, free T(4), and antithyroid peroxidase, only age (standardized coefficient = 0.39; P = 0.0001) and TSH (standardized coefficient = 0.41; P < 0.0002) were significantly related to serum CXCL10 levels. We conclude that circulating CXCL10 is increased in patients with AT and is associated with hypothyroidism. CXCL10 may be regarded as a marker of a more aggressive thyroiditis leading to thyroid destruction.     

Human monoclonal antibody as prophylaxis for SARS coronavirus infection in ferrets

SARS coronavirus continues to cause sporadic cases of severe acute respiratory syndrome (SARS) in China. No active or passive immunoprophylaxis for disease induced by SARS coronavirus is available. We investigated prophylaxis of SARS coronavirus infection with a neutralising human monoclonal antibody in ferrets, which can be readily infected with the virus. Prophylactic administration of the monoclonal antibody at 10 mg/kg reduced replication of SARS coronavirus in the lungs of infected ferrets by 3.3 logs (95% CI 2.6-4.0 logs; p<0.001), completely prevented the development of SARS coronavirus-induced macroscopic lung pathology (p=0.013), and abolished shedding of virus in pharyngeal secretions. The data generated in this animal model show that administration of a human monoclonal antibody might offer a feasible and effective prophylaxis for the control of human SARS coronavirus infection.     

<Emphasis Type="Italic">Pseudomonas aeruginosa</Emphasis> carriage,colonization, and infection in ICU patients

Objective We evaluated whether Pseudomonas aeruginosa associated nosocomial infections in our ICU originate mainly from patients' endogenous flora or from exogenous cross-transmission. Design and setting A 6-month prospective surveillance survey was performed according to standardized protocols at the interdisciplinary ICU of the Azienda Ospedaliera Cannizzaro. Patients The study analyzed 121 patients and focused on three different states: carriage upon admission, colonization of sterile sites, and infections during ICU stay. Results We identified 138 P. aeruginosa isolates from 45 patients. The cumulative incidence of P. aeruginosa sustained colonization in the ICU was 29.9/100 patients, and the incidence density was 16.2/1,000 patient-days. The cumulative incidence of P. aeruginosa-sustained infections in the ICU was 36.7/100 patients, and the incidence density was 19.9/1,000 patient-days. The most frequent infection type was ventilator-associated pneumonia. PFGE analysis of P. aeruginosa isolates led to the identification of a major clone represented by 60.8% of isolates involving 45.9% of patients. The impact of cross-transmission, i.e., the preventable proportion of P. aeruginosa acquisition, was estimated to be at least 59.5% of all colonization or infection episodes. Acquisition of multidrug-resistant P. aeruginosa was significantly associated with cross-transmission. Conclusions Our results suggest that the ICU personnel and environment served as reservoirs for cross-transmission and emphasize the importance of exogenous acquisition of multidrug-resistant P. aeruginosa, of reduction in antibiotic pressure, and prompt enforcement of infection control measures. This work was supported by grants to A. A. from the University of Catania, Italy.