Machine learning-supported interpretation of kidney graft elementary lesions in combination with clinical data.

Interpretation of kidney graft biopsies using the Banff classification is still heterogeneous. In this study, extreme gradient boosting classifiers learned from two large training datasets (n = 631 and 304 cases) where the "reference diagnoses" were not strictly defined following the Banff rules but from central reading by expert pathologists and further interpreted consensually by experienced transplant nephrologists, in light of the clinical context. In three external validation datasets (n = 3744, 589, and 360), the classifiers yielded a mean ROC curve AUC (95%CI) of: 0.

Noninvasive Diagnosis of Acute Rejection in Renal Transplant Patients Using Mass Spectrometric Analysis of Urine Samples: A Multicenter Diagnostic Phase III Trial.

Unlabelled: Timely recognition and treatment of acute kidney graft rejection is important to prevent premature graft failure. A predefined urinary marker set for acute T cell-mediated rejection (TCMR) containing 14 peptides was tested for this purpose in a multicenter in-place validation study.

Methods: Three hundred twenty-nine prospectively collected and 306 archived urine samples from 11 transplant centers in Germany, France, and Belgium were examined.

Natural Compound Library Screening Identifies New Molecules for the Treatment of Cardiac Fibrosis and Diastolic Dysfunction.

Background: Myocardial fibrosis is a hallmark of cardiac remodeling and functionally involved in heart failure development, a leading cause of deaths worldwide. Clinically, no therapeutic strategy is available that specifically attenuates maladaptive responses of cardiac fibroblasts, the effector cells of fibrosis in the heart. Therefore, our aim was to develop novel antifibrotic therapeutics based on naturally derived substance library screens for the treatment of cardiac fibrosis.

[Acute on chronic renal failure in a 62-year-old man with ANCA-associated vasculitis].

We describe a patient with ANCA (antineutrophil cytoplasmic antibodies) associated vasculitis and acute-on-chronic renal failure. He had initially presented with severe pulmonary hemorrhage and anuric renal failure and improved rapidly with immunosuppressive therapy. Repeat renal biopsy revealed candida interstitial nephritis.

Activation of Peroxisome Proliferator-Activated Receptor-δ as Novel Therapeutic Strategy to Prevent In-Stent Restenosis and Stent Thrombosis.

Objective: Drug-eluting coronary stents reduce restenosis rate and late lumen loss compared with bare-metal stents; however, drug-eluting coronary stents may delay vascular healing and increase late stent thrombosis. The peroxisome proliferator-activated receptor-delta (PPARδ) exhibits actions that could favorably influence outcomes after drug-eluting coronary stents placement.

Approach And Results: Here, we report that PPARδ ligand-coated stents strongly reduce the development of neointima and luminal narrowing in a rabbit model of experimental atherosclerosis.

Pulmonary Metastases of a Uterine Smooth Muscle Tumour with Undefined Malignancy Potential.

Smooth muscle neoplasms with atypical proliferative behaviour, but without clear histopathological malignancy represent a diagnostic and therapeutic challenge, as distinction from a sarcoma can be difficult and no guaranteed treatment recommendations are available due to the rarity of these changes. In the event of uncertain primary histology, even metastases cannot be assessed as malignancy criteria, but may contribute to the clarification of the histology. Similarities with other smooth muscle proliferations, such as lymphangioleiomyomatosis, are striking.

Disease-associated miRNA-mRNA networks in oral lichen planus.

Background: A large number of pathophysiological mechanisms are regulated by microRNAs (miRNAs), which represent a new class of posttranscriptional regulators of gene expression. To date, little is known about their role in oral lichen planus (OLP), a chronic inflammatory mucocutaneous disease of unknown etiology which is being discussed as a potentially premalignant condition of oropharyngeal cancer. The aim of the present investigation was to assess the pathophysiological impact of miRNAs and to determine regulatory miRNA networks which are directly linked to potentially disease-associated target transcripts in OLP.

Comparison of two different absorbable membranes for the coverage of lateral osteotomy sites in maxillary sinus augmentation: a preliminary study.

Introduction: Barrier membranes, both absorbable and non-absorbable, have been used in sinus augmentation for many years. Some years ago, a new autologous blood substrate called Platelet-Rich-Fibrin (PRF) was introduced, and to date, the supporting effect on bone regeneration has been controversial. This study aimed to evaluate the effect of PRF on bone regeneration when used as a barrier membrane at the lateral osteotomy site in sinus augmentation.

Impact of an interleukin-1 receptor antagonist and erythropoietin on experimental myocardial ischemia/reperfusion injury.

Background: Revascularization of infarcted myocardium results in release of inflammatory cytokines mediating myocardial reperfusion injury and heart failure. Blockage of inflammatory pathways dampens myocardial injury and reduces infarct size. We compared the impact of the interleukin-1 receptor antagonist Anakinra and erythropoietin on myocardial ischemia/reperfusion injury.

Percutaneous pulmonary valve replacement: autologous tissue-engineered valved stents.

Aims: Percutaneous implantation has already been used clinically and is a great option for treating young patients. The use of autologous tissue-engineered valved stents might solve the problem of degeneration and limited durability of biological heart valves.

Methods And Results: Porcine pulmonary heart valves and small intestinal submucosa were obtained from a slaughterhouse.

Complement activation in angiotensin II-induced organ damage.

We tested whether or not complement activation participates in angiotensin (Ang) II-induced vasculopathy. We used double transgenic rats harboring human renin and angiotensinogen genes (dTGR) with or without losartan or the human renin inhibitor aliskiren. Sprague-Dawley (SD) rats were controls.

The effect of pharmacological doses of different antioxidants on oxidation parameters and atherogenesis in hyperlipidaemic rabbits.

The oxidation hypothesis of atherosclerosis implies that antioxidants are able to inhibit lipoprotein oxidation in the arterial wall and thereby retard atherogenesis. Since most of the animal studies performed have used very high doses of antioxidants, it is to date unknown whether antioxidants are effective antiatherosclerotic agents when given in pharmacological doses. Here we addressed this question using homozygous Watanabe heritable hyperlipidaemic (WHHL) rabbits as an animal model of atherosclerosis.

Effects of pravastatin on cholesterol metabolism of cholesterol-fed heterozygous WHHL rabbits.

1. We administered the 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor pravastatin at a daily dose of 1 mg kg(-1) body weight to cholesterol-fed (0.03%) heterozygous Watanabe heritable hyperlipidaemic rabbits, an animal model for heterozygous familial hypercholesterolaemia.

Effects of low-dose pravastatin sodium on plasma cholesterol levels and aortic atherosclerosis of heterozygous WHHL rabbits fed a low cholesterol (0.03%) enriched diet for one year.

The aim of this study was to evaluate the cholesterol-lowering and antiatherosclerotic effect of the HMG-CoA reductase inhibitor pravastatin sodium at a dosage comparable to human therapy. Twelve heterozygous WHHL rabbits (13 months old) were fed 100 g per day of a low cholesterol (0.03%) enriched diet for 12 months.

Whole plasma oxidation assay as a measure of lipoprotein oxidizability.

Lipoprotein oxidation induced in vitro in whole plasma is expected to be a more relevant model of the lipoprotein oxidation in the arterial wall than the in vitro oxidation of single isolated lipoproteins, e.g., low density lipoprotein (LDL).

Probucol inhibits not only the progression of atherosclerotic disease, but causes a different composition of atherosclerotic lesions in WHHL-rabbits.

Watanabe heritable hyperlipidaemic (WHHL)-rabbits develop premature atherosclerosis due to an inborn defect of the low-density lipoprotein (LDL) receptor causing severe hypercholesterolaemia. Probucol, which possesses a lipid lowering and an antioxidative potency, has been shown to reduce the extent of atherosclerotic disease in this animal. The object of the present study was the detailed analysis of the cellular and non-cellular composition of atherosclerotic lesions in WHHL-rabbits treated with probucol when compared with untreated controls.