Protochordate concordant xenotransplantation settings reveal outbreaks of donor cells and divergent life span traits

If fulminate rejection in allogeneic and xenogeneic engraftments is not an evolutionary relict feature, then any treatment that ablates the host surveillance's effector arms capabilities and eliminates graft vs. host reactivity should induce donor chimerism in transplant settings. We demonstrate here marked proliferative response of Botryllus (Urochordata) blood cells months following their infusions (2×10⁴–10⁵ blood cells per host) into the concordant xenogeneic environment of irradiated Botrylloides soma. The state of infused cells was followed by Botryllus specific microsatellite alleles on DNA samples from host zooids and vascular system. Increased growth rates and life spans of engrafted hosts in some cases, and sudden chimerical death following the outbreak of donor cells in others, indicate a ‘double-edged sword’ expression of concurrent evolutionary selected mechanisms. This DES phenomenon in immunity underlies divergent stem cell competition phenomena in multicellular organisms, leading in mammals, to cases of autoimmune diseases vis-à-vis long-lasting microchimerism events following an iatrogenic transplantation.     

Hybrid Interventional Procedures in Congenital Heart Disease

The evolution of congenital cardiac surgery has seen significant innovative advances in collaborative efforts between congenital cardiac surgeons and interventionalists to provide the least invasive intervention with the greatest hemodynamic benefit for patients with congenital heart disease. This review looks at how this collaborative approach has evolved and is being applied to treat a number of congenital conditions across the age ranges.     

Hemorrhagic complications in patients treated with anticoagulant doses of a low molecular weight heparin (enoxaparin) in routine hospital practice.

Low molecular weight heparins (LMWHs) are a rapidly growing class of anticoagulant drug. Their efficacy has been demonstrated in several clinical settings where they are rapidly becoming the anticoagulant of choice. Controlled clinical studies in patients with deep vein thrombosis, pulmonary embolism, and unstable angina have documented that the frequency of major hemorrhage is 0.5-4%. The purpose of the study was to determine the frequency of minor and major hemorrhage occurring in patients receiving anticoagulant doses of an LMWH (enoxaparin) during routine clinical practice. A prospective, observational study of consecutive patients receiving enoxaparin 1 mg/kg twice daily for at least 24 hours in five internal medicine wards of a university teaching hospital was performed. Five hundred forty-nine patients were studied. The mean age was 67.5+/-15.5 years and the mean duration of enoxaparin therapy was 3.8+/-1.5 days. Hemorrhage was documented in a total of 94 patients (17.3%). Major hemorrhage occurred in 14 patients (2.6%), injection-site hemorrhage occurred in 55 patients (10%), and minor hemorrhage (noninjection site) was documented in 25 patients (4.7%). There were two deaths attributed to hemorrhage. Patients with major hemorrhage were older than patients with minor or no hemorrhage (75.5+/-10.4 versus 66.8+/-15.2 years; p=0.03) and occurred in patients receiving enoxaparin for a longer period (5.14+/-3.8 days) than those with minor (4+/-2.5 days) or no hemorrhage (2.9+/-2.1 days). Major hemorrhage was significantly associated with impaired renal function, chronic liver disease, and concomitant treatment with warfarin or a proton pump inhibitor. Enoxaparin used in anticoagulant doses in unselected medical patients is not associated with more major hemorrhagic complications than observed in controlled clinical trials. Major hemorrhage may be more likely in older patients, in patients with chronic liver disease and impaired renal function, in patients receiving prolonged enoxaparin therapy, and in patients receiving warfarin or proton pump inhibitors.     

Diffusion-weighted magnetic resonance enterography for prediction of response to tumor necrosis factor inhibitors in stricturing Crohn’s disease

Background and aims

Distinguishing between fibrotic and inflammatory strictures in Crohn’s disease (CD) is still challenging. The capacity of diffusion-weighted (DWI) magnetic resonance (MRE) to identify intestinal fibrosis was recently demonstrated; however, the therapeutic implications of this association have never been evaluated. The aim of the current study was to identify imaging features, including DWI, which can predict response to anti-inflammatory treatment in patients with stricturing CD.

Methods

Consecutive CD patients with intestinal strictures that initiated treatment with anti-tumor necrosis alpha (anti-TNF) between June 2012 and April 2017 with MRE adjacent to treatment onset were retrospectively collected. The primary outcome was treatment failure, defined as drug discontinuation, CD-related surgery, or endoscopic dilatation of the stricture. Clinical, demographic, and imaging data were compared between patients who did and did not develop treatment failure within 12 months of anti-TNF treatment initiation.

Results

A total of 21 patients were included in the study; 9/21 (42.8%) developed treatment failure. None of the clinical/demographic parameters were associated with the risk of treatment failure. Among imaging parameters, only ADC value (< 1 × 10⁻³ mm²/s) was significantly associated with the risk of treatment failure (AUC = 0.81, 66% vs. 0%, p = 0.015).

Conclusions

Our results suggest that ADC value on DWI MRE may predict the risk of treatment failure in stricturing CD. If replicated in larger studies, these results may guide therapeutic decisions and suggest avoiding anti-TNF treatment.

     

Evolving role of endoscopy in inflammatory bowel disease: Going beyond diagnosis

Inflammatory bowel disease, encompassing Crohn’s disease (CD) and ulcerative colitis, are chronic immune-mediated inflammatory bowel diseases (IBD) that primarily affect the gastrointestinal tract with periods of activity and remission. Large body of evidence exist to strengthen the prognostic role of endoscopic evaluation for both disease activity and severity and it remains the gold standard for the assessment of mucosal healing. Mucosal healing has been associated with improved clinical outcomes with prolonged remission, decreased hospitalization, IBD-related surgeries and colorectal cancer risk. Therefore, endoscopic objectives in IBD have been incorporated as part of standard care. With the known increased risk of colorectal cancer in IBD, although prevention strategies continue to develop, regular surveillance for early detection of neoplasia continue to be paramount in IBD patients’ care. It is thanks to evolving technology and visualization techniques that surveillance strategies are continuously advancing. Therapeutic endoscopic options in IBD have also been expanding, from surgery sparing therapies such as balloon dilation of fibrostenotic strictures in CD to endoscopic mucosal resection of neoplastic lesions. In this review article, we discuss the current evidence on the use of endoscopy as part of standard of care of IBD, its role in surveillance of neoplasia, and the role of interventional endoscopic therapies.