Infliximab treatment influences the serological expression of matrix metalloproteinase (MMP)-2 and -9 in Crohn's disease

BACKGROUND: Matrix metalloproteinases (MMPs) are actively involved in the pathogenesis of Crohn's disease (CD). We assessed the effect of the anti-tumor necrosis factor-alpha (TNF-alpha) monoclonal antibody infliximab on the in vitro and in vivo expression of MMP-2 and MMP-9 in CD. METHODS: Infliximab-treated fistulizing (n = 10) or active disease (n = 7) CD patients, from an in-house study, and fistulizing CD patients (n = 42) and active CD patients (n = 24) from 2 placebo controlled studies were evaluated for serum MMP levels and clinical response. Biopsies were evaluated immunohistochemically for the MMPs. Whole blood cultures stimulated with lipopolysaccharide (LPS)/infliximab were evaluated for MMP mRNA and protein levels. RESULTS: Serum MMP-2 levels in CD patients increased during follow-up, similarly in responders and nonresponders, by infliximab. Immunohistochemistry showed no clear MMP-2 change in biopsies. Serum MMP-9 levels, however, showed a consistent pattern of decrease in most CD patients, particularly in those responding, and MMP-9-positive polymorphonuclear leukocytes in biopsies also decreased by infliximab. LPS stimulation of whole blood increased the MMP-9 levels in plasma significantly in CD patients and controls, but infliximab had no effect on the secretion. Long-term LPS stimulation raised leukocyte MMP-9 mRNA levels 16-fold and infliximab inhibited this induction by 80%. CONCLUSIONS: Infliximab treatment increases MMP-2 and decreases MMP-9 in serum of patients with CD, the latter also in the intestine, which extends and confirms our previous ex vivo explants observations. However, these changes were not strictly associated with the response to treatment. The enhanced leukocyte MMP-9 expression in CD seems to be regulated by TNF-alpha.     

High impact of depression in heart failure: early diagnosis and treatment options

Depressive syndromes in chronic heart failure (CHF) are common and are associated with a poorer prognosis, particularly with increased morbidity and mortality. CHF as a severe physical disorder may increase the risk of developing depressive syndromes or vice-versa as an interaction of possible common psycho-organic etiological aspects. Depression in CHF is associated with impaired NYHA status and daily activities, resulting in enhanced hospitalisation rates and medical costs with a great impact on long-term health. Only a fraction of comorbid patients receives antidepressants. Therefore, identification of risk factors and prevention by optimizing cardiological and psychiatric therapeutic strategies appear essential for these patients. Early diagnosis and treatment of both CHF and depression may prevent further pathophysiological effects on the heart and brain. This review gives a comprehensive overview of the occurrence, risk factors and shared pathophysiology of depression in CHF, and focuses on improving insufficient diagnosis and therapy of depression. Special attention is given on the cardiac effects of psychopharmacological and alternate non-pharmacological antidepressant therapy in CHF. Recommendations are made for treating depression in CHF patients for a better prevention of this disabling physical and psychosocial condition.     

Blood pressure response to chronic intake of coffee and caffeine: a meta-analysis of randomized controlled trials

PURPOSE: Coffee is a widely consumed beverage and small health effects of substances in coffee may have large public health consequences. It has been suggested that caffeine in coffee increases the risk of hypertension. We performed a meta-analysis of randomized controlled trials of coffee or caffeine and blood pressure (BP). DATA IDENTIFICATION: BP trials of coffee or caffeine published between January 1966 and January 2003 were identified through literature databases and manual search. STUDY SELECTION: A total of 16 studies with a randomized, controlled design and at least 7 days of intervention was selected, comprising 25 strata and 1010 subjects. DATA EXTRACTION: Two persons independently obtained data on sample size, type and duration of intervention, changes in BP and heart rate (HR), and subjects' characteristics for each trial. Meta-analysis was performed using a random-effects model. RESULTS: A significant rise of 2.04 mmHg [95% confidence interval (CI), 1.10-2.99] in systolic BP and 0.73 mmHg (95% CI, 0.14-1.31) in diastolic BP was found after pooling of coffee and caffeine trials. When coffee trials (n = 18, median intake: 725 ml/day) and caffeine trials (n = 7, median dose: 410 mg/day) were analysed separately, BP elevations appeared to be larger for caffeine [systolic: 4.16 mmHg (2.13-6.20); diastolic: 2.41 mmHg (0.98-3.84)] than for coffee [systolic: 1.22 mmHg (0.52-1.92) and diastolic: 0.49 mmHg (-0.06-1.04)]. Effects on HR were negligible. CONCLUSIONS: Regular caffeine intake increases BP. When ingested through coffee, however, the blood pressure effect of caffeine is small.     

Serum biomarkers in idiopathic pulmonary fibrosis

Within the group of Idiopathic Interstitial Pneumonias (IIPs), above all Idiopathic Pulmonary Fibrosis (IPF) poses a considerable diagnostic and therapeutic problem. Although genetic profiling indicates that IPF, Non Specific Interstitial Pneumonia (NSIP), and chronic hypersensitivity pneumonitis (HP) are distinctly different diseases, in every day practice these diseases can be difficult to tell apart. Furthermore, treatment of these diseases is notoriously difficult. Serum biomarkers reflect our understanding of the underlying pathogenesis and potentially fulfill a role in establishing a diagnosis, prognosis and therapy. While no single biomarker is currently able to accurately predict the presence or absence of an IIP, a composite of several markers holds promise for the future. Several biomarkers, such as KL-6, surfactant proteins and circulating fibrocytes, appear to contribute to our insight into disease progression and prognosis. It is however uncertain whether these markers give us additional information to common diagnostic tests and their value has as yet to be validated for every day practice. Fortunately, the potential of biomarkers is increasingly recognized and biomarker data are prospectively gathered in current placebo-controlled therapeutic trials.     

A Cluster Randomised Trial to Determine the Efficacy of the “<Emphasis Type="Italic">Feeding Buddies</Emphasis>” Programme in Improving Exclusive Breastfeeding Rates Among HIV-Infected Women in Rural KwaZulu-Natal,South Africa

This cluster randomised trial in KwaZulu-Natal South Africa, evaluated the implementation of a Feeding Buddies (FB) programme to improve exclusive breastfeeding (EBF) amongst human immunodeficiency virus infected mothers. Eight clinics were randomly allocated to intervention and control arms respectively. Pregnant women attending the prevention of mother-to-child transmission program and intending to EBF were enrolled: control (n = 326), intervention (n = 299). Intervention mothers selected FBs to support them and they were trained together (four sessions). Interviews of mothers occurred prenatally and at post-natal visits (day 3, weeks 6, 14 and 22). Breastfeeding results were analysed (Stata) as interval-censored time-to-event data, with up to four time intervals per mother. EBF rates at the final interview were similar for control and intervention groups: 44.68% (105/235) and 42.75% (109/255) respectively (p = 0.67). In Cox regression analysis better EBF rates were observed in mothers who received the appropriate training (p = 0.036), had a community care giver visit (p = 0.044), while controlling for other factors. Implementation realities reduced the potential effectiveness of the FBs.     

Risk factors and impact of major bleeding in critically ill patients receiving heparin thromboprophylaxis

Purpose

Bleeding frequently complicates critical illness and may have serious consequences. Our objectives are to describe the predictors of major bleeding and the association between bleeding and mortality in medical–surgical critically ill patients receiving heparin thromboprophylaxis.

Methods

We prospectively studied patients from 67 intensive care units and six countries enrolled in a thromboprophylaxis trial (NCT00182143) comparing dalteparin with unfractionated heparin. Patients with trauma, orthopedic surgery or neurosurgery were excluded. Trained research coordinators used a validated tool to document bleeding, which underwent duplicate independent blinded adjudication. Major bleeding was defined as hypovolemic shock, bleeding into critical sites, requiring an invasive intervention or transfusion of at least two units of red blood cells, or associated with hypotension or tachycardia in the absence of other causes. Adjusted Cox proportional hazard regression analysis was used to identify major bleeding predictors and the association between bleeding and mortality.

Results

Among 3,746 patients, bleeding occurred in 208 [5.6 %, 95 % confidence interval (CI) 4.9–6.3 %]. Time-dependent predictors were prolonged activated partial thromboplastin time [hazard ratio (HR) 1.10, 1.05–1.14 per 10 s increase], lower platelet count (HR 1.16, 1.09–1.24 per 50 × 10⁹/L decrease), therapeutic heparin (HR 3.26, 1.72–6.17), antiplatelet agents (HR 1.38, 1.02–1.88), renal replacement therapy (HR 1.75, 1.20–2.56), and recent surgery (HR 1.64, 1.01–2.65). Type of pharmacologic thromboprophylaxis was not associated with bleeding. Patients with bleeding had a higher risk of in-hospital death (HR 2.09, 1.69–2.57).

Conclusions

As major bleeding has modifiable risk factors and is associated with in-hospital mortality, strategies to mitigate these factors should be evaluated in critically ill patients.     

Improving Inhibitory Control Abilities (ImpulsE)—A Promising Approach to Treat Impulsive Eating?

Although there is preliminary evidence that inhibitory control training improves impulsive eating, less is known about the effects on eating behaviour and weight loss in clinical samples. Sixty‐nine treatment‐seeking adults with obesity (binge‐eating disorder 33.3%; other specific feeding and eating disorders 40.6%) were randomly blockwise allocated to ImpulsE, an intervention to improve inhibitory control and emotion regulation abilities or a guideline‐appropriate cognitive behavioural therapy (CBT)‐based treatment as usual. Self‐reported and performance‐based impulsivity, eating disorder pathology and BMI were compared at baseline (T1), post‐treatment (T2) and 1‐ or 3‐month follow‐up. ImpulsE led to better food‐specific inhibition performance (p = .004), but groups did not differ regarding improvements in global Eating Disorder Examination Questionnaire (EDE‐Q) score at T2. At 3‐month follow‐up, binge eaters benefited most from ImpulsE (p = .028) and completers of ImpulsE demonstrated a significantly greater weight reduction (p = .030). The current findings propose ImpulsE as a promising approach to treat obesity, illustrating acceptability and additional benefits for course of weight. Copyright © 2017 John Wiley & Sons, Ltd and Eating Disorders Association.