Ovarian Non-Hodgkin Lymphoma Revealed by Bone Metastasis: A Rare Pediatric Case.

Ovary involvement of non-Hodgkin lymphoma (NHL) is rare. We report a rare case of ovarian NHL during adolescence revealed by bone metastasis. The diagnosis of malignant lymphoma was established after adnexectomy and histological study of the excised tissue. The tumor was classified as a diffuse large B-cell lymphoma. The patient has been treated according to the LMB French protocol with good outcome after two years. Although NHL is a rare ovarian neoplasm, it is essential to establish an accurate diagnosis as early as possible for therapeutic purposes.

Comparative study of tissue adhesive therapy versus band ligation in control of actively bleeding esophageal varices.

BACKGROUND AND STUDY AIMS: Bleeding esophageal varices is a common life-threatening emergency that carries a significant morbidity and mortality. Acute variceal bleeding is considered active when spurting and/or oozing varix is seen at the time of endoscopy, or inactive in the presence of large esophageal varices with blood in the stomach with no other bleeding source at the time of endoscopy. Aim: comparing endoscopic variceal ligation (EVL) versus cyanoacrylate injection (CI) in active esophageal variceal bleeding control. PATIENTS AND METHODS: a retrospective single tertiary center study from April 2014 to February 2018, including 401 patients with active esophageal variceal bleeding. RESULTS: Endoscopic hemostasis was achieved by both endoscopic variceal ligation in 182 patients (91.9%) and cyanoacrylate injection in 197 patients (97.05%) without significant difference (P value 0. 15). Re-bleeding occurred more frequently in EVL group 20 patients (10.1%) compared to 14 patients (6.9%) in CI (P value 0.01). Early six-week Mortality was higher among EVL group (20.7%) compared to CI (17.2%) without statistical significance (P value 0.3). CONCLUSION: Both EVL and CI are almost as effective in achieving endoscopic hemostasis. CI is more effective, feasible, and could be used as a salvage therapy and/or spared for risky active bleeding esophageal varices.

Acute coronary syndrome remodels the antiplatelet aggregation properties of HDL particle subclasses.

Essentials HDL subclasses were studied in acute coronary syndrome (ACS). HDL2 from ACS patients have better antiplatelet potency than HDL from non ACS subjects. ACS remodels the antiplatelet properties of HDL subclasses. Oxidized polyunsaturated fatty acids content of HDL is modified by ACS. SUMMARY: Background Although HDLs have antithrombotic effects by reducing platelet activation, the relationship between HDL levels and the risk of acute coronary syndrome (ACS) is unclear, as HDL particles are heterogeneous in composition and biological properties. Objective To characterize the effects of HDL2 and HDL3 subclasses from ACS patients and non-coronary artery disease (CAD) subjects on platelet activation. Methods We measured platelet aggregation and ex vivo thrombus formation, analyzed signaling pathways by flow cytometry, and performed a targeted lipidomics analysis on HDL subclasses. Results Analysis of human platelet aggregation in suspension, adhesion on von Willebrand factor and thrombus formation on collagen under arterial shear demonstrated that HDL2 from ACS patients had higher antiplatelet potency than HDL3 from ACS patients and HDL from non-CAD subjects. HDL binding to scavenger receptor class B type I was essential for this effect. A lipidomics analysis revealed that HDL2 from ACS patients had more oxidized polyunsaturated fatty acids (PUFAs). An inverse correlation between the concentrations of 9-hydroxyoctadecadienoic acid (9-HODE), 13-hydroxyoctadecadienoic acid (13-HODE), the eicosapentaenoic acid metabolite 18-hydroxyeicosapentaenoic acid (18-HEPE) and hydroxyeicosatetraenoic acid isomers in HDL2 and platelet aggregation was observed. This relationship was further demonstrated by the direct inhibitory effects of 18-HEPE, 9-HODE, 13-HODE, 17-hydroxydocosahexaenoic acid and 14-hydroxydocosahexaenoic acid on collagen-related peptide-induced platelet aggregation, indicating that oxidized PUFAs contribute to the antithrombotic effect of ACS HDL2. Conclusions Our data shed new light on the antiplatelet effects of HDL subclasses, and suggest physiological adaptation through the modulation of HDL properties in ACS patients that may limit their platelet-dependent thrombotic risk.

A decision support model to predict the presence of an acute infiltrate on chest radiograph.

A chest infiltrate is needed to make a diagnosis of community-acquired pneumonia, but chest X-rays might be time consuming, entail radiation exposure, and demand resources that are not always available. We sought to derive a model to predict whether a patient will have an infiltrate on chest X-ray (CXR). This prospective observational study included patients visiting the Emergency Department of Beilinson Hospital in the years 2003-2004 (derivation cohort) and 2010-2011 (validation cohort), who had undergone a CXR, and were suspected of having a respiratory infection. We excluded all patients with possible healthcare associated infections. A logistic regression model was derived and applied to the validation cohort. A total of 1,555 patients met inclusion criteria: 993 in the derivation cohort and 562 in the validation cohort with 287 (29%) and 226 (40%) having an infiltrate, respectively. The derivation model area-under-the curve (AUC) was 0.79 (95% CI 0.76-0.82). We categorized the patients into three groups-presence or absence of infiltrate, or undetermined. In the validation cohort, 70 (12%) patients were classified as 'no infiltrate'; 3 (4%) of them had an infiltrate, 367 (65%) were classified as 'infiltrate'; 190 (52%) of them had an infiltrate on CXR, and 125 (46%) were classified as 'undetermined'; 33 (26%) of them with an infiltrate on CXR. Using this prediction model for the evaluation of patients with suspected respiratory infection in an ED setting may help avoid over 10% of CXRs.

Therapeutic Hypothermia in Asphyxiated Neonates: Experience from Neonatal Intensive Care Unit of University Hospital of Marrakech.

INTRODUCTION: Therapeutic hypothermia (TH) is now recommended for the treatment neonates with hypoxic-ischemic encephalopathy (HIE). This treatment protocol is applied in our department since June 2012. The aim of this study is to report the first experience with head cooling in asphyxiated neonates in Morocco. PATIENTS AND METHODS: Prospective study of newborns admitted for HIE from July 18, 2012, to May 15, 2014, in Neonatal Intensive Care Unit (NICU) of Mohamed VI University Hospital. The results were studied by comparing a newborn group who received hypothermia to a control group. RESULTS: Seventy-two cases of neonates with perinatal asphyxia were admitted in the unit. According to inclusion criteria thirty-eight cases were eligible for the study. Only 19 cases have received the hypothermia protocol for different reason; the arrival beyond six hours of life was the main cause accounting for 41%. Complications of asphyxia were comparable in both groups with greater pulmonary hypertension recorded in the control group. The long-term follow-up of protocol group was normal in almost half of cases. CONCLUSION: Our first experience with the controlled TH supports its beneficial effect in newborns with HIE. This treatment must be available in all the centers involved in the neonatal care in Morocco.

Intramyocardial transplantation of mesenchymal stromal cells for chronic myocardial ischemia and impaired left ventricular function: Results of the MESAMI 1 pilot trial.

BACKGROUND: The MESAMI 1 trial was a bicentric pilot study designed to test the feasibility and safety of intramyocardially injected autologous bone marrow-derived mesenchymal stromal cells (MSCs) for the treatment of ischemic cardiomyopathy. METHODS AND RESULTS: The study included 10 patients with chronic myocardial ischemia, left ventricular (LV) ejection fractions (EFs) of ≤35%, and reversible perfusion defects who were on stable optimal medical therapy and were not candidates for revascularization. MSCs (mean: 61.5×10(6) cells per patient) were injected into 10-16 viable sites at the border of the LV scar via a NOGA-guided catheter. Both primary endpoints, feasibility (successful harvest, expansion, and injection of autologous MSCs) and safety (absence of severe adverse events [SAEs]) were met in all 10 patients at the 1-month follow-up time point, and none of the SAEs reported during the full 2-year follow-up period were attributable to the study intervention. The results of secondary efficacy endpoint analyses identified significant improvements from baseline to Month 12 in LVEF (29.4±2.0% versus 35.7±2.5%; p=0.003), LV end-systolic volume (167.8±18.8mL versus 156.1±28.6mL; p=0.04), 6-min walk test and NYHA functional class. CONCLUSIONS: Our results suggest that autologous MSCs can be safely administered to the hearts of patients with severe, chronic, reversible myocardial ischemia and impaired cardiac function and may be associated with improvements in cardiac performance, LV remodeling, and patient functional status. A randomized, double blind, multicenter, placebo-controlled clinical trial (MESAMI 2) will evaluate the efficacy of this treatment approach in a larger patient population. CLINICAL TRIAL REGISTRATION: Unique identifier: NCT01076920.

[Characteristics and management of ST-elevation myocardial infarction in France: Regional variations in 2010]. / Prise en charge du syndrome coronaire aigu avec sus-décalage de ST en France : variations régionales en 2010.

Data on regional variations in the characteristics, management and early outcome of patients admitted with ST-elevation myocardial infarction (STEMI) in France are limited. We used data from the FAST-MI 2010 registry to determine whether regional specificities existed, dividing the French territory into 6 larger geographical regions. Variations in the patients' characteristics were found, partly related to regional variations in demography. Acute reperfusion strategy showed more use of primary percutaneous coronary intervention in the greater Paris area, compared to other regions, which would be expected owing to geography and local availability of catheterization laboratories. Overall, however, in-hospital management showed more similarities than differences across regions. Complications, and in particular in-hospital mortality, did not differ significantly among regions.

Life or death by NFκB, Losartan promotes survival in dy2J/dy2J mouse of MDC1A.

Inflammation and fibrosis are well-defined mechanisms involved in the pathogenesis of the incurable Laminin α2-deficient congenital muscular dystrophy (MDC1A), while apoptosis mechanism is barely discussed. Our previous study showed treatment with Losartan, an angiotensin II type I receptor antagonist, improved muscle strength and reduced fibrosis through transforming growth factor beta (TGF-ß) and mitogen-activated protein kinases (MAPK) signaling inhibition in the dy(2J)/dy(2J) mouse model of MDC1A. Here we show for the first time that Losartan treatment up-regulates and shifts the nuclear factor kappa B (NFκB) signaling pathway to favor survival versus apoptosis/damage in this animal model. Losartan treatment was associated with significantly increased serum tumor necrosis factor alpha (TNF-α) level, p65 nuclei accumulation, and decreased muscle IκB-ß protein level, indicating NFκB activation. Moreover, NFκB anti-apoptotic target genes TNF receptor-associated factor 1 (TRAF1), TNF receptor-associated factor 2 (TRAF2), cellular inhibitor of apoptosis (cIAP2), and Ferritin heavy chain (FTH1) were increased following Losartan treatment. Losartan induced protein expression toward a pro-survival profile as BCL-2 expression levels were increased and Caspase-3 expression levels were decreased. Muscle apoptosis reduction was further confirmed using terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling (TUNEL) assay. Thus, along with TGF-ß and MAPK signaling, NFκB serves as an important regulatory pathway which following Losartan treatment promotes survival in the dy(2J)/dy(2J) mouse model of MDC1A.

In-flight automatic detection of vigilance states using a single EEG channel.

Sleepiness and fatigue can reach particularly high levels during long-haul overnight flights. Under these conditions, voluntary or even involuntary sleep periods may occur, increasing the risk of accidents. The aim of this study was to assess the performance of an in-flight automatic detection system of low-vigilance states using a single electroencephalogram channel. Fourteen healthy pilots voluntarily wore a miniaturized brain electrical activity recording device during long-haul flights ( 10 ±2.0 h, Atlantic 2 and Falcon 50 M, French naval aviation). No subject was disturbed by the equipment. Seven pilots experienced at least a period of voluntary ( 26.8 ±8.0 min, n = 4) or involuntary sleep (N1 sleep stage, 26.6 ±18.7 s, n = 7) during the flight. Automatic classification (wake/sleep) by the algorithm was made for 10-s epochs (O1-M2 or C3-M2 channel), based on comparison of means to detect changes in α, ß, and θ relative power, or ratio [( α+θ)/ß], or fuzzy logic fusion (α, ß). Pertinence and prognostic of the algorithm were determined using epoch-by-epoch comparison with visual-scoring (two blinded readers, AASM rules). The best concordance between automatic detection and visual-scoring was observed within the O1-M2 channel, using the ratio [( α+θ )/ß] ( 98.3 ±4.1% of good detection, K = 0.94 ±0.07, with a 0.04 ±0.04 false positive rate and a 0.87 ±0.10 true positive rate). Our results confirm the efficiency of a miniaturized single electroencephalographic channel recording device, associated with an automatic detection algorithm, in order to detect low-vigilance states during real flights.

No post-conditioning in the human heart with thrombolysis in myocardial infarction flow 2-3 on admission.

AIMS: Proof-of-concept evidence suggests that mechanical ischaemic post-conditioning (PostC) reduces infarct size when applied immediately after culprit coronary artery re-opening in ST-elevation myocardial infarction (STEMI) patients with thrombolysis in myocardial infarction 0-1 (TIMI 0-1) flow grade at admission. Whether PostC might also be protective in patients with a TIMI 2-3 flow grade on admission (corresponding to a delayed application of the post-conditioning algorithm) remains undetermined. METHODS AND RESULTS: In this multi-centre, randomized, single-blinded, controlled study, STEMI patients with a 2-3 TIMI coronary flow grade at admission underwent direct stenting of the culprit lesion, followed (PostC group) or not (control group) by four cycles of (1 min inflation/1 min deflation) of the angioplasty balloon to trigger post-conditioning. Infarct size was assessed both by cardiac magnetic resonance at Day 5 (primary endpoint) and cardiac enzymes release (secondary endpoint). Ninety-nine patients were prospectively enrolled. Baseline characteristics were comparable between control and PostC groups. Despite comparable size of area at risk (AAR) (38 ± 12 vs. 38 ± 13% of the LV circumference, respectively, P = 0.89) and similar time from onset to intervention (249 ± 148 vs. 263 ± 209 min, respectively, P = 0.93) in the two groups, PostC did not significantly reduce cardiac magnetic resonance infarct size (23 ± 17 and 21 ± 18 g in the treated vs. control group, respectively, P = 0.64). Similar results were found when using creatine kinase and troponin I release, even after adjustment for the size of the AAR. CONCLUSION: This study shows that infarct size reduction by mechanical ischaemic PostC is lost when applied to patients with a TIMI 2-3 flow grade at admission. This indicates that the timing of the protective intervention with respect to the onset of reperfusion is a key factor for preventing lethal reperfusion injury in STEMI patients. CLINICAL TRIAL NUMBER: NCT01483755.

[Pulmonary embolism in young adults. Think of homocysteine]. / Embolie pulmonaire de l'adulte jeune. Penser à l'homocystéine.

Two cases of severe pulmonary embolism in young adults are presented. Biological investigation disclosed hyperhomocysteinemia. This highlights the great interest of homocysteine quantification in such clinical events.

Role of protein kinase C δ in ER stress and apoptosis induced by oxidized LDL in human vascular smooth muscle cells.

During atherogenesis, excess amounts of low-density lipoproteins (LDL) accumulate in the subendothelial space where they undergo oxidative modifications. Oxidized LDL (oxLDL) alter the fragile balance between survival and death of vascular smooth muscle cells (VSMC) thereby leading to plaque instability and finally to atherothrombotic events. As protein kinase C δ (PKCδ) is pro-apoptotic in many cell types, we investigated its potential role in the regulation of VSMC apoptosis induced by oxLDL. We found that human VSMC silenced for PKCδ exhibited a protection towards oxLDL-induced apoptosis. OxLDL triggered the activation of PKCδ as shown by its phosphorylation and nuclear translocation. PKCδ activation was dependent on the reactive oxygen species generated by oxLDL. Moreover, we demonstrated that PKCδ participates in oxLDL-induced endoplasmic reticulum (ER) stress-dependent apoptotic signaling mainly through the IRE1α/JNK pathway. Finally, the role of PKCδ in the development of atherosclerosis was supported by immunohistological analyses showing the colocalization of activated PKCδ with ER stress and lipid peroxidation markers in human atherosclerotic lesions. These findings highlight a role for PKCδ as a key regulator of oxLDL-induced ER stress-mediated apoptosis in VSMC, which may contribute to atherosclerotic plaque instability and rupture.

Asymmetric adaptation to indolic and aliphatic glucosinolates in the B and Q sibling species of Bemisia tabaci (Hemiptera: Aleyrodidae).

The role glucosinolates play in defending plants against phloem feeders such as aphids and whiteflies is currently not clear as these herbivores may avoid bringing glucosinolates from the phloem sap into contact with myrosinase enzymes. Here, we investigated the effects of high levels of aliphatic and indolic glucosinolates on life history traits and detoxification gene expression in two sibling species, B and Q, of the whitefly Bemisia tabaci. High levels of aliphatic glucosinolates decreased the average oviposition rate of both species and reduced the survival and developmental rate of Q nymphs. High levels of indolic glucosinolates decreased the oviposition rate and survival of nymphal stages of the B species and the developmental rate of both species. Molecular analyses revealed two major asymmetries between the B and Q species. First, specific GST genes (BtGST1 and BtGST2) were significantly induced during exposure to indolic glucosinolates only in Q. This may reflect the genes putative involvement in indolic glucosinolates detoxification and explain the species' good performance on plants accumulating indolic glucosinolates. Second, the constitutive expression of eight of the 10 detoxification genes analysed was higher in the Q species than in the B species. Interestingly, four of these genes were induced in B in response to high levels of glucosinolates. It seems, therefore, that the B and Q species differ in their 'optimal defence strategy'. B utilizes inducible defences that are profitable if the probability of experiencing the stress is small and its severity is low, while Q invests significant resources in being always 'ready' for a challenge.

Consensus statement on the care of the hyperglycaemic/diabetic patient during and in the immediate follow-up of acute coronary syndrome.

The Diabetes and Cardiovascular Disease study group of the Société francophone du diabète (SFD, French Society of Diabetes) in collaboration with the Société française de cardiologie (SFC, French Society of Cardiology) have devised a consensus statement on the care of the hyperglycaemic/diabetic patient during and in the immediate follow-up of acute coronary syndrome (ACS); in particular, it includes the different phases of ACS [the intensive care unit (ICU) period, the post-ICU period and the short-term follow-up period after discharge, including cardiac rehabilitation] and also embraces all of the various diagnostic and therapeutic issues with a view to optimizing the collaboration between cardiologists and diabetologists. As regards diagnosis, subjects with HbA(1c) greater or equal to 6.5% on admission may be considered diabetic while, in those with no known diabetes and HbA(1c) less than 6.5%, it is recommended that an OGTT be performed 7 to 28 days after ACS. During hospitalization in the ICU, continuous insulin treatment should be initiated in all patients when admission blood glucose levels are greater or equal to 180 mg/dL (10.0 mmol/L) and, in those with previously known diabetes, when preprandial glucose levels are greater or equal to 140 mg/dL (7.77 mmol/L) during follow-up. The recommended blood glucose target is 140-180 mg/dL (7.7-10 mmol/L) for most patients. Following the ICU period, insulin treatment is not mandatory for every patient, and other antidiabetic treatments may be considered, with the choice of optimal treatment depending on the metabolic profile of the patient. Patients should be referred to a diabetologist before discharge from hospital in cases of unknown diabetes diagnosed during ACS hospitalization, of HbA(1c) greater or equal to 8% at the time of admission, or newly introduced insulin therapy or severe/repeated hypoglycaemia. Referral to a diabetologist after hospital discharge is recommended if diabetes is diagnosed by the OGTT, or during cardiac rehabilitation in cases of uncontrolled diabetes (HbA(1c) ≥ 8%) or severe/repeated hypoglycaemia.

Consensus statement on the care of the hyperglycaemic/diabetic patient during and in the immediate follow-up of acute coronary syndrome.

The Diabetes and Cardiovascular Disease study group of the Société francophone du diabète (SFD, French Society of Diabetes) in collaboration with the Société française de cardiologie (SFC, French Society of Cardiology) have devised a consensus statement on the care of the hyperglycaemic/diabetic patient during and in the immediate follow-up of acute coronary syndrome (ACS); in particular, it includes the different phases of ACS [the intensive care unit (ICU) period, the post-ICU period and the short-term follow-up period after discharge, including cardiac rehabilitation] and also embraces all of the various diagnostic and therapeutic issues with a view to optimalizing the collaboration between cardiologists and diabetologists. As regards diagnosis, subjects with HbA(1c) greater or equal to 6.5% on admission may be considered diabetic while, in those with no known diabetes and HbA(1c) less than 6.5%, it is recommended that an OGTT be performed 7 to 28days after ACS. During hospitalization in the ICU, continuous insulin treatment should be initiated in all patients when admission blood glucose levels are greater or equal to 180mg/dL (10.0mmol/L) and, in those with previously known diabetes, when preprandial glucose levels are greater or equal to 140mg/dL (7.77mmol/L) during follow-up. The recommended blood glucose target is 140-180mg/dL (7.7-10mmol/L) for most patients. Following the ICU period, insulin treatment is not mandatory for every patient, and other antidiabetic treatments may be considered, with the choice of optimal treatment depending on the metabolic profile of the patient. Patients should be referred to a diabetologist before discharge from hospital in cases of unknown diabetes diagnosed during ACS hospitalization, of HbA(1c) greater or equal to 8% at the time of admission, or newly introduced insulin therapy or severe/repeated hypoglycaemia. Referral to a diabetologist after hospital discharge is recommended if diabetes is diagnosed by the OGTT, or during cardiac rehabilitation in cases of uncontrolled diabetes (HbA(1c)≥8%) or severe/repeated hypoglycaemia.

Plaque rupture and morphological characteristics of the culprit lesion in acute coronary syndromes without significant angiographic lesion: analysis by intravascular ultrasound.

PURPOSE: To evaluate by intravascular ultrasound (IVUS) the characteristics of the culprit lesion with plaque rupture without significant angiographic stenosis after acute coronary syndromes (ACS). PATIENTS AND METHODS: After ACS, IVUS was performed in 68 patients (46.8 years±11.9) without significant angiographic stenosis (31±15%). Plaque rupture was defined as a cavity within the plaque, communicating with the arterial lumen and having an overlying residual fibrous cap fragment. Qualitative analysis defined the type of plaque, and quantitative analysis evaluated plaque plus media area, plaque volume, plaque burden, and arterial remodeling index. Patients were divided into two groups: Group I with plaque rupture (25 patients) and Group II without plaque rupture (43 patients). RESULTS: All patients with rupture showed soft or mixed plaque but no calcified plaque. In Group I, plaque rupture was associated with a larger plaque burden (49.8±12.3% vs. 39.8±12.1%, P<.0005), a more significant plaque plus media area (7.44±2.9 vs. 5.24±2.4mm(2), P<.001), a greater plaque volume (151.9±103.4 vs. 99.2±81.6mm(3), P<.007), and a higher ratio of plaque volume over length (8.0±3.8 vs. 5.6±3.7mm(3)/mm, P<.003). In Group I, positive remodeling was more frequent than intermediate remodeling (P<.03) or negative remodeling (P<.005). In Group II, there was no significant difference between the three types of remodeling. CONCLUSION: The plaque ruptures responsible for ACS frequently appear on voluminous plaques with a large plaque burden and positive arterial remodeling.

Asymmetry in thermal tolerance trade-offs between the B and Q sibling species of Bemisia tabaci (Hemiptera: Aleyrodidae).

We investigated life history trade-offs related to thermal tolerance in two sibling species, commonly referred to as the B and Q biotypes, of Bemisia tabaci. We focused on basal resistance to short unpredicted heat stress, which reflects the organism investment, during both optimal and stressful conditions, in insuring its survival. At 27 °C, the relative reproductive performance of B was seven-fold higher than Q. After short stress of 42 °C, these differences increased to 23-fold. A turnover took place after short stress of 43 and 45 °C, in which Q adults performed better. As the expression of the analysed Hsp70 and other stress-related genes was found to be higher in the Q species, our data likely reflects two different strategies for optimal performance. B lowers soma protection for achieving maximum reproduction ('direct inhibitory' trade-off model), whereas Q invests significant resources in being always 'ready' for a challenge.