Discovery and Validation of a Urinary Exosome mRNA Signature for the Diagnosis of Human Kidney Transplant Rejection

BackgroundDeveloping a noninvasive clinical test to accurately diagnose kidney allograft rejection is critical to improve allograft outcomes. Urinary exosomes, tiny vesicles released into the urine that carry parent cells’ proteins and nucleic acids, reflect the biologic function of the parent cells within the kidney, including immune cells. Their stability in urine makes them a potentially powerful tool for liquid biopsy and a noninvasive diagnostic biomarker for kidney-transplant rejection.MethodsUsing 192 of 220 urine samples with matched biopsy samples from 175 patients who underwent a clinically indicated kidney-transplant biopsy, we isolated urinary exosomal mRNAs and developed rejection signatures on the basis of differential gene expression. We used crossvalidation to assess the performance of the signatures on multiple data subsets.ResultsAn exosomal mRNA signature discriminated between biopsy samples from patients with all-cause rejection and those with no rejection, yielding an area under the curve (AUC) of 0.93 (95% CI, 0.87 to 0.98), which is significantly better than the current standard of care (increase in eGFR AUC of 0.57; 95% CI, 0.49 to 0.65). The exosome-based signature’s negative predictive value was 93.3% and its positive predictive value was 86.2%. Using the same approach, we identified an additional gene signature that discriminated patients with T cell–mediated rejection from those with antibody-mediated rejection (with an AUC of 0.87; 95% CI, 0.76 to 0.97). This signature’s negative predictive value was 90.6% and its positive predictive value was 77.8%.ConclusionsOur findings show that mRNA signatures derived from urinary exosomes represent a powerful and noninvasive tool to screen for kidney allograft rejection. This finding has the potential to assist clinicians in therapeutic decision making.     

Clinical and laboratory characteristics in septic arthritis patients with and without isolated germs

Background

The management of septic arthritis without bacteriological evidence is not well codified.

Impact of sertraline on weight,waist circumference and glycemic control: A prospective clinical trial on depressive diabetic type 2 patients

Aim

Depression is prevalent in patients with type 2 diabetes. It may have a negative impact on the management of diabetes mellitus and could affect weight. The main aim of the investigation was to evaluate the effect of antidepressant treatment (sertraline) on anthropometric variables and glycemic control in depressed type 2 diabetic patients.

Dorsal costo-vertebral joint as a rare localization of Staphylococcus aureus sepsis

Background

Septic arthritis of the costovertebral thoracic joint is a rare site infection. We report an isolated case of septic arthritis of the 10th costo-vertebral right joint with osteitis due to Staphylococcus aureus.

Spontaneous pneumothorax and Recklinghausen's disease: a case report

The Von Recklinghausen disease is a genetic hereditary neurofibromatosis. It causes neurofibroma, axillary and inguinal lentigines, and café-au-lait spots in the skin. It may affect the lung in 5 to 20% of cases, causing neurofibroma, infiltrative and cystic lesions, emphysematous or bubble injury leading to a chronic respiratory failure. The risk of pneumothorax in theses cases seems higher. Few reviews reported the pulmonary manifestations in the Recklinghausen disease and specially the pneumothorax as a complication while the direct relation between this neurofibromatosis and the lung disease is not clearly established yet. We report a case report of spontaneous pneumothorax with slow evolution complicating the course of a patient with Recklinghausen disease.     

Platelet reactivity evaluated with the VASP assay following ticagrelor loading dose in acute coronary syndrome patients undergoing percutaneous coronary intervention

Background

The level of platelet reactivity (PR) inhibition obtained after P2Y12-ADP receptor antagonist loading dose (LD) is associated with the ischemic and bleeding risk following percutaneous coronary intervention (PCI) in acute coronary syndromes (ACS).

Objective

We aimed to evaluate the level of PR inhibition achieved by a 180 mg LD of ticagrelor and the rate of high on-treatment platelet reactivity (HTPR) in ACS patients undergoing PCI.

Methods

We performed a multicentre prospective observational study enrolling ACS patients undergoing PCI. Patients were included if they were admitted for ST-elevation myocardial infarction or non ST-elevation ACS. To assess PR, a VASP index was measured at least 6 and within 24 hours following a 180 mg LD of ticagrelor. HTPR was defined as a VASP index ≥ 50%.

Results

One hundred and fifteen patients were included: 31.3% of STEMI, 49.6% of NSTEMI and 19.1% of unstable angina. Following ticagrelor LD the mean VASP index was 17 ± 14%. However the response to ticagrelor was not uniform with a small inter-individual variability: inter quartile range: 7.6–22.8% and a rate of HTPR of 3.5%. A high number of patients, 65.6%, had a VASP index < 16%. None of the baseline characteristics of the study population was associated with PR. In addition, PR was similar in STEMI, NSTEMI and unstable angina (p = 0.9).

Conclusion

In ACS patients the level of PR inhibition achieved by a 180 mg loading dose of ticagrelor is not uniform and the rate of HTPR is 3.5%. A high proportion of patients exhibited a VASP index < 16%.