Long-term mucosal recovery and healing in celiac disease is the rule – not the exception

Objective: The prevalence of persistent villous atrophy (VA) in patients with celiac disease (CD) on a gluten-free diet (GFD) varies greatly between studies. Most studies show a relatively high prevalence of mucosal atrophy and inflammation in treated patients, a finding which have led to a concept of non-responsive CD. Few studies have examined the prevalence of long-term mucosal healing. Our study aimed to determine the extent of mucosal healing in a cohort of Norwegian patients with CD treated with GFD for several years.

Materials and methods: Adult patients diagnosed with VA between 1989 and 2009 were included. We performed a follow-up gastroscopy with duodenal biopsies. Two pathologists evaluated the biopsies according to the Marsh–Oberhuber classification. Mucosal healing was defined as Marsh 0 while mucosal recovery was defined as Marsh 0-2.

Results: Duodenal biopsies were obtained from 127 adult patients with established CD. After a follow-up time of 8.1 years (median, range 2.3–22.3), 103 (81%) of the patients showed mucosal healing, 120 patients (94%) showed mucosal recovery, and 7 patients (6%) showed persistent VA. In addition, 103 of the 127 patients (81%) had undergone a routine follow-up biopsy 12.6 months (median, range 5.2–28.8) after diagnosis. At the time of the routine follow-up, only 52 of these patients (50.5%) had achieved mucosal recovery.

Conclusions: Although half of the patients had persistent VA at the time of routine follow-up, both long-term mucosal recovery and healing is possible for the vast majority of adult patients with CD.     

Opening mitochondrial KATP in the heart – what happens, and what does not happen

There is considerable evidence that opening the mitochondrial ATP-sensitive potassium channel (mitoK_ATP) is cardioprotective in ischemia-reperfusion. Two prominent questions surround the role of mitoK_ATP in the cardiomyocyte: How does opening mitoK_ATP protect? What is the normal physiological role of mitoK_ATP in the heart? Before these questions can be addressed, it is necessary to agree on the bioenergetic consequences of opening mitoK_ATP, and this distills down to a single question – does opening mitoK_ATP cause significant uncoupling or not? The evidence strongly indicates that it does not and that reports of uncoupling and inhibition of Ca²⁺ uptake are the result of using toxic concentrations of K_ATP channel openers. Thus, opening mitoK_ATP results in increased K⁺ flux that is sufficient to change mitochondrial volume but is insufficient to cause significant depolarization of membrane potential. The volume changes, however, have significant bioenergetic consequences for energy coupling in the cell.     

Case reports – When bronchial obstruction in the young adult is not asthma and inhalers do not help

Introduction: Localised bronchial obstruction is a rare differential diagnosis to asthma. Case study: We describe two younger patients treated unsuccessfully for asthma and eventually diagnosed with localised bronchoconstriction. Results: Bronchoscopy revealed bronchoconstriction: Tracheobronchomalacia in case 1 and fixed obstruction in case 2. Conclusion: A systematic approach to the asthma patient with absent response to therapy facilitates rational use of therapeutic and diagnostic resources.     

High-sensitive cardiac troponin T is not always heart – Paraneoplastic systemic sclerosis simulated myocardial ischemia

BackgroundThe high-sensitive cardiac troponin T (hs-cTnT, Elecsys^®) is an excellent and worldwide used diagnostic marker for myocardial ischemia with high sensitivity. However, elevated hs-cTnT levels are found in different systemic diseases and can lead to misdiagnosis. The high-sensitive cardiac troponin I (hs-cTnI, ARCHITECT^®) shows comparable sensitivity. However, hs-cTnI is much more specific than hs-cTnT (92% vs. 80%, 99th percentile).Case summaryAn asymptomatic women with a cancer of unknown primary (CUP) presented constantly high hs-cTnT. Electrocardiogram, echocardiography as well as cardiac MRI and CT angiography of the coronary arteries showed no pathological findings. Accordingly, the measurement of the more specific hs-cTnI showed no significant increase. A repeated clinical examination revealed a localized scleroderma and autoimmune antibody pattern diagnosed a paraneoplastic systemic sclerosis (SSc). Therefore, a treatment with Rituximab — a CD20 antibody — was initiated, which reduced activity of SSc and also concentration of hs-cTnT.ConclusionIn the present case, a localized scleroderma due a paraneoplastic SSc was accompanied by elevated hs-cTnT levels in the absence of cardiovascular disease. A reduced inflammation of skeletal muscle tissue due to rituximab treatment decreased hs-cTnT levels. This is the first report of an occult hs-cTnT elevation due to paraneoplastic SSc.     

Nonsteroidal anti-inflammatory drugs and the heart: what is the danger?

Nonsteroidal anti-inflammatory drugs (NSAIDs) and selective cyclooxygenase (COX-2) inhibitors, or "coxibs," are used for a number of disease conditions for relief of pain and inflammation. Currently available data suggest concern for prothrombotic risk with coxibs and some NSAIDs, and the magnitude of risk may vary with individual agents. NSAIDs and coxibs also increase blood pressure, worsen hypertension control, and may precipitate heart failure, with important differences among agents. Physicians should consider patterns of risk and benefit in selecting the most appropriate agent for individual patients based on the individual gastrointestinal and cardiovascular risk profile.     

What is the athlete's heart?

The different components of the cardiovascular system adapt to the stress related to physical training. These adaptations, mainly functional and partly morphological, concern both the heart and the vessels. They play a key role in physical performance improvement, especially in case of endurance sports.     

CRP is or is not a reliable marker of ischaemic heart disease?

In recent years a growing body of evidence has emphasized the role of C-reactive protein (CRP) as a marker of future cardiovascular events. CRP is a pentameric molecule widely utilized as a marker of infections and inflammation. The evidence that inflammation plays an important role in the pathogenesis of coronary artery disease and in plaque destabilization has lead to use of CRP as a marker of cardiovascular disease as well. First described as a component of the inflammatory pathway in acute coronary syndromes, CRP has been consistently found to be associated with the risk of future events in no-ST elevation acute coronary syndromes, independently of other risk factors, including troponine. Subsequently CRP has been described as a powerful marker of risk of future events in large populations of apparently healthy subjects. So far there is very little doubt that CRP represents a reliable marker of cardiovascular events, but some issues remain unanswered such as why CRP is a good marker of cardiovascular events and whether or not a better inflammatory marker exists. It must be stressed that CRP, because of its analytical and biological properties and the large amount of available data, is the only inflammatory marker accepted for clinical use.     

Remote ischemic preconditioning with – but not without – metabolic support protects the neonatal porcine heart against ischemia-reperfusion injury

Background

While remote ischemic preconditioning (rIPC) protects the mature heart against ischemia-reperfusion (IR) injury, the effect on the neonatal heart is not known. The neonatal heart relies almost solely on carbohydrate metabolism, which is modified by rIPC in the mature heart. We hypothesized that rIPC combined with metabolic support with glucose-insulin (GI) infusion improves cardiac function and reduces infarct size after IR injury in neonatal piglets in-vivo.

Methods and results

32 newborn piglets were randomized into 4 groups: control, GI, GI + rIPC and rIPC. GI and GI + rIPC groups received GI infusion continuously from 40 min prior to ischemia. rIPC and GI + rIPC groups underwent four cycles of 5 min limb ischemia. Myocardial IR injury was induced by 40 min occlusion of the left anterior descending artery followed by 2 h reperfusion. Myocardial lactate concentrations were assessed in microdialysis samples analyzed by mass spectrometry. Infarct size was measured using triphenyltetrazolium chloride staining. Systolic recovery (dP/dt_max as % of baseline) after 2 h reperfusion was 68.5 ± 13.8% in control, 53.7 ± 11.2% in rIPC (p < 0.05), and improved in GI (83.6 ± 18.8%, p < 0.05) and GI + rIPC (87.0 ± 15.7%, p < 0.01).

Conclusion

rIPC + GI protects the neonatal porcine heart against IR injury in-vivo. rIPC alone has detrimental metabolic and functional effects that are abrogated by simultaneous GI infusion.     

Stem cells for the heart, are we there yet?

Although several repair mechanisms have been described in the human heart, all fall too short to prevent clinical heart disease in most acute or chronic pathological cardiac conditions. Moreover, despite many breakthroughs in cardiovascular medicine, the complications of a myocardial infarction such as chronic heart failure remains a serious worldwide problem. Bone marrow stem cells could provide for a promising strategy to restore myocardial infarctions and prevent postinfarct congestive heart failure, because there is growing body of evidence that bone marrow stem cells, such as mesenchymal stem cells, can generate new cardiomyocytes in animals and humans. In this review, we will discuss important issues on stem cell therapy for cardiac regeneration after myocardial infarction, which might be of paramount importance when considering future human trials.