Post-transfusion acute lung injury (Trali) after plasma infusion in a patient having a constitutional thrombotic microangiopathy

INTRODUCTION: Transfusion-related acute lung injury is a post-transfusion interstitial lung injury. CASE REPORT: We reported a post-transfusion acute lung injury in a 23-years old woman having a chronic thrombotic microangiopathy related to an ADAMTS 13 constitutional deficiency receiving monthly plasma infusion for six years. The temporal relationship between the lung injury and the infusion of fresh frozen plasma led to the diagnosis of transfusion-related acute lung injury. The finding in the donor of the transfused plasma of an anti-HLA class II antibody recognizing HLA-DR52 present on leucocytes of the recipient suggests a causal relationship between this antigen-antibody conflict and the triggering of the TRALI. This chronic pathologic state requiring monthly plasma transfusions for thrombotic accident prevention raises the question of the selection of plasma obtained from non-immunized donors. CONCLUSION: The occurrence of a post transfusion pulmonary edema without cardio-vascular overload, must lead to consider a TRALI especially in predisposing clinical situations. In the case reported the role of constitutional ADAMTS 13 deficiency in genesis of TRALI is considered.     

Report of a family segregating mutations in both the <Emphasis Type="Italic">APC</Emphasis> and <Emphasis Type="Italic">MSH2</Emphasis> genes: juvenile onset of colorectal cancer in a double heterozygote

Background and aims  Mutations in DNA mismatch repair genes are associated with high risk of digestive malignancies [hereditary non-polyposis colorectal cancer (HNPCC); Lynch syndrome]; mutations of APC and MYH are associated with classic and attenuated familial adenomatous polyposis (FAP). Although the early onset of tumors in both syndromes is characteristic of their genetic origin, pediatric malignancies remain rare. Certain reports have found familial colorectal cancer (CRC) occurring in very young patients associated with mutations in more than one gene. Materials and method  A family corresponding to the Amsterdam criteria for HNPCC, including two cases of colorectal cancer before the age of 25 years, was analyzed for mutations in the MSH2 genes by sequencing. Because polyposis was observed in a patient who developed CRC at age 16, the APC gene was also sequenced. Results  A truncating mutation in the MSH2 gene, c.258_259delTG, was carried by patients developing cancer of the colon (two patients), uterus, kidney, bladder, and/or small intestine at ages 16, 24, 43, 44, 45, and 57, respectively. A patient with CRC at age 16 was found to carry the APC c.3183_3187del5 mutation as well as the MSH2 mutation, and it is inferred that her father, deceased of CRC at age 24, was also a double heterozygote. Interpretation  These results confirm that vigilance is required when interpreting molecular results for families with very young patients, as more than one gene may contribute to the genetic risk. Cancer screening measures must also be adapted to the earlier and more penetrant risk to double heterozygotes.     

Lysyl oxidase-like protein-2 regulates sprouting angiogenesis and type IV collagen assembly in the endothelial basement membrane

Sprouting angiogenesis is associated with extensive extracellular matrix (ECM) remodeling. The molecular mechanisms involved in building the vascular microenvironment and its impact on capillary formation remain elusive. We therefore performed a proteomic analysis of ECM from endothelial cells maintained in hypoxia, a major stimulator of angiogenesis. Here, we report the characterization of lysyl oxidase-like protein-2 (LOXL2) as a hypoxia-target expressed in neovessels and accumulated in the endothelial ECM. LOXL2 belongs to the lysyl oxidase family of secreted enzymes involved in ECM crosslinking. Knockdown experiments in Tg(fli1:egfp)y1 zebrafish embryos resulted in lack of intersegmental vessel circulation and demonstrated LOXL2 involvement in proper capillary formation. Further investigation in vitro by loss and gain of function experiments confirmed that LOXL2 was required for tubulogenesis in 3D fibrin gels and demonstrated that this enzyme was required for collagen IV assembly in the ECM. In addition, LOXL2 depletion down-regulated cell migration and proliferation. These data suggest a major role for LOXL2 in the organization of endothelial basal lamina and in the downstream mechanotransductive signaling. Altogether, our study provides the first evidence for the role of LOXL2 in regulating angiogenesis through collagen IV scaffolding.     

Glycoprotein IIb/IIIa inhibitors use in the setting of primary percutaneous coronary intervention for ST elevation myocardial infarction in patients pre‐treated with newer P2Y12 inhibitors

ObjectivesWe sought to investigate the safety and potential benefit of administrating glycoprotein IIb‐IIIa inhibitors (GPIs) on top of more potent P2Y12 inhibitors.BackgroundA number of clinical trials, performed at a time when pretreatment and potent platelet inhibition was not part of routine clinical practice, have documented clinical benefits of GPI in ST‐segment elevation myocardial infarction (STEMI) patients at the cost of a higher risk of bleeding.MethodsWe used the data of a prospective, ongoing registry of patients admitted for STEMI in our center. For the purpose of this study only patients presenting for primary percutaneous coronary intervention and pretreated with new P2Y12 inhibitors (prasugrel or ticagrelor) were included. We compared patients who received GPI with those who did not.ResultsEight hundred twenty‐four STEMI patients were included in our registry; GPIs were used in 338 patients (41%). GPI patients presented more often with cardiogenic shock and Thrombolysis in myocardial infarction (TIMI) flow grade <3. GPI use was not associated with an increase in in‐hospital or 3‐month mortality. Bleeding endpoints were similar in both groups.ConclusionsOur study suggests that GPI may be used safely in combination with recent P2Y12 inhibitors in STEMI patients in association with modern primary percutaneous coronary intervention strategies (radial access and anticoagulation with enoxaparin) with similar bleeding and mortality rates at hospital discharge and 3‐month follow‐up.     

Effect of the number of pregraft blood transfusions in kidney graft recipients treated with bioreagents and cyclosporin A

Abstract. The impact of a systematic, nondonor-specific, pregraft blood transfusion (BT) protocol was evaluated retrospectively in 446 consecutive, first renal transplant recipients with regard to graft survival rate, rejection, and incidence of infectious episodes. Cyclosporin A was the maintenance immunosuppressive treatment in all patients after a 2-week course of antithymocyte globulin or anti-IL-2 monoclonal antibody. Recipients were assigned to three groups according to the number of pregraft BT (one or two, three or four, or more than four). When nonimmunological failures were excluded from the study, patients receiving three or four BT had statistically better graft survival ( P < 0.02) and a lower incidence of rejection episodes ( P < 0.05) than those in the other groups. There were no significant differences between the three groups in the distribution of HLA mismatching (A, B and DR), time interval between the last BT and transplantation, DR6 recipient phenotype, or nonimmunological failures. Our results show that the number of pregraft BT is an important factor in transplantation.     

Comparison of dysplasia profiles in stimulated ovaries and in those with a genetic risk for ovarian cancer

AimOvarian epithelial dysplasia (OED) was first described after prophylactic oophorectomy for genetic risk of ovarian cancer. In light of Fathalla’s incessant ovulation theory, this study was set up to describe the presence of ovarian abnormalities (dysplasia) after ovulation induction and to compare dysplasia profiles in stimulated and genetic risk ovaries.MethodsOne-hundred and twenty-four patients who had undergone salpingo-oophorectomies or ovarian cystectomies between 1990 and 2005 were reviewed. They were divided into three groups: (1) previous in vitro fertilisation (n = 35); (2) prophylactic oophorectomies for genetic risk (n = 27) and (3) fertile non-cancerous controls (n = 62). Eleven cytological and architectural epithelial features were defined and a dysplasia score was calculated to quantify ovarian epithelial abnormalities.ResultsMean dysplasia score was significantly higher in the genetic risk and stimulated ovary groups than in controls (9.55 versus 3.62, p < 0.0001; 7.51 versus 3.62, p < 0.0002, respectively). Cytological and architectural abnormalities were more frequent in the genetic risk group, while the profile of abnormalities was different in the genetic risk and stimulated groups.ConclusionsThese findings support a possible relationship between OED and the use of ovulation-stimulating drugs. The increased dysplasia score in stimulated and genetic risk ovaries might be consistent with progression towards neoplastic transformation, and may justify the use of the term dysplasia or intraepithelial ovarian neoplasia. The observation of dysplasia in the stimulated group may differentiate women at risk. Conversely, the fact that the dysplasia profile after stimulation differs from that in genetic risk ovaries suggests that ovarian stimulation may predispose to a different evolution.     

Pleural carcinogenic potency of mineral fibers (asbestos, attapulgite) and their cytotoxicity on cultured cells

The carcinogenicity of several samples of mineral fibers was tested following injection of 20 mg in the pleural cavity of noninbred Sprague-Dawley rats. Three samples of chrysotile asbestos (mean length: 3.2, 2.1, and 1.2 micron) induced mesotheliomas at a rate of 48, 52, and 19%, respectively. The first sample was acid leached prior to intrapleural injection; in that group, the percentage of mesotheliomas was reduced to 25%. Treatment with amosite and crocidolite resulted in the occurrence of 57 and 56% of mesotheliomas. Acid-treatment of amphiboles did not significantly modify the percentage of mesotheliomas. When the Stanton's fiber dimensions were taken into consideration to correlate with mesothelioma incidence, the observed number of mesotheliomas in the chrysotile-treated animals was much lower than that expected, suggesting that other fiber parameters (chemistry, physicochemistry) play a role in the carcinogenicity. Attapulgite fibers (mean length: 0.77 micron) did not induce tumor, and the mean survival time was of the same order as that observed in the control groups. The injection of quartz resulted in no mesothelioma but did result in 6 malignant histiocytic lymphomas (17%) and 2 malignant schwannomas (6%). In vitro experiments did not show strong correlation between cytotoxicity and the carcinogenic potency of these minerals, but the qualitative cellular responses might give some indications on the fiber's potency. In addition, the in vitro effects of the fibers seem to be modulated by their size.