A Massive Venlafaxine Intoxication: Evolution of Cardiac Toxicity with Venlafaxine and O-Desmethylvenlafaxine Elimination Kinetics: A Grand Round.

BACKGROUND: This study presents the case of a 19-year-old woman who attempted suicide by ingesting 11.25 g of venlafaxine (V). She was admitted to the hospital with severe biventricular dysfunction, progressing to cardiac arrest requiring extracorporeal circulatory life support for 11 days. The pharmacokinetics of venlafaxine during impaired cardiac output and the effect of its active metabolite, the O-desmethylvenlafaxine (ODV), are currently not very well understood. METHODS AND RESULTS: Serum concentrations of V and ODV were monitored twice daily for 3 weeks. The maximum concentrations of venlafaxine and ODV were at 14 hours after ingestion, with 29,180 mcg/L for V and 5399 mcg/L for ODV. Half-lives increased, requiring 2 weeks to eliminate the drug. The left ventricular ejection fraction significantly improved when V + ODV was below 1000 mcg/L and remained altered until the ODV concentrations were lower than 400 mcg/L. CONCLUSIONS: This report, with complete elimination kinetic of V and ODV in a monodrug intoxication, provides information about the modification of pharmacokinetics in the case of an overdose managed by extracorporeal circulatory life support, the cardiac toxicity of ODV, and the value of the toxic threshold for the active moiety.

Clues of incomplete reversal of heparin in cardiac surgery.

OBJECTIVES: In our center, an unusual rate of patients had abnormalities of hemostasis in immediate postoperative period of cardiac surgery. Our objectives were to identify the cause of these sudden hemostasis abnormalities and to evaluate the performances of point of care coagulation testing. METHODS: In this prospective and descriptive study, we included 33 consecutive patients undergoing elective cardiac surgery for 1 month. Heparin-induced anticoagulation and calculation of the protamine dose were tested by the Hemostasis Management System Plus device (Medtronic, Minneapolis, MN, USA). Fifteen minutes after the end of the protamine infusion, activated clotting time (ACT), activated partial thromboplastin time and anti Xa activity were measured. In case of unusual clinical bleeding, a Quantra analysis (Stago, HemoSonics LLC, Charlottesville, VA) was added. RESULTS: Residual antiXa activity >0.2 IU/mL after neutralization was present in 44% of patients. Our investigation concluded incomplete heparin reversal. There was no association between cellular reinfusate and the presence of heparin. The unusual rate of hemostasis abnormalities was explained by a less efficient protamine reversal of heparin. ACT and Clot Time Ratio (CTR, Quantra system) correlated with AntiXa with Spearman's coefficients of 0.85 (p < .0001) and 0.95 (p = .0012), respectively. About ACT, a threshold of 150 seconds had a sensitivity of 85% [58-97] and a specificity of 85% [58-97%] for detection of AntiXa>0.2. For CTR, a threshold of 1.4 had a sensitivity of 67% [30-94] and a specificity of 100% [18-100]. CONCLUSION: The use of point of care coagulation testing is effective in detecting incomplete reversal of heparin.

Normal values of proximal aorta diameters in healthy Sub Saharan Africans: The TAHES study.

OBJECTIVES: Reported ranges of normal values are mostly issued from studies performed with Caucasians. This study is a part of TAHES, a population-based prospective cohort study in Benin and aims to establish normal reference values for echocardiographic diameters of the proximal aorta in Africans. METHODS: Transthoracic echocardiography (TTE) examinations were performed by four cardiologists following pre-defined protocols, and analyzed off-line by a single observer. Aortic root diameters were measured during diastole for sinuses of Vasalva (SV), sinotubular junction (STJ) and proximal ascending aorta (AA), and during systole for annulus. Upper limits were defined as the 95th percentiles. RESULTS: We included 513 normotensive, non-diabetic, and cardiovascular disease-free individuals (206 men, 307 women, age 40 ± 14 years). The diameters of the proximal aorta were significantly greater in men. The inner-edge-to-inner-edge non-indexed upper values for the annulus, SV, STJ and AA were respectively 25, 34, 28.5, 32 mm in men and 22, 30, 26, 30 mm in women. The leading-edge-to-leading-edge upper values were respectively 38, 35, 36 for men and 34, 33, 32 mm for women. No significant differences between sexes were recorded for body surface area (BSA)-indexed diameters of the annulus, STJ and AA. BSA-indexed SV dimension was greater in men than women were. SV, STJ, AA indexed-diameters correlated with age in both sexes but not for annulus indexed-diameter. CONCLUSION: Normal values from a general population in West Africa could to differ from those established in Caucasian populations. Ethnic-specific reference diameters are here proposed for appropriate diagnosis of proximal aortic diseases in sub-Saharan Africa.

Postpandemic Influenza Mortality of Venovenous Extracorporeal Membrane Oxygenation-Treated Patients in Reunion Island: A Retrospective Single Center Study.

OBJECTIVES: The aim of the present study was to assess the post-pandemic mortality of influenza in patients receiving venovenous extracorporeal membrane oxygenation (VV-ECMO) in Reunion Island, France, by comparing the incidence with other patients undergoing VV-ECMO. DESIGN: Retrospective, descriptive, and single-center cohort study. The primary outcome was the standardized mortality ratio for influenza based on the quartiles of the Respiratory Extracorporeal Membrane Oxygenation Survival Prediction score (RESP Score) in the reference population of patients undergoing VV-ECMO. SETTING: Intensive care unit (ICU), Felix Guyon Hospital, University Teaching Hospital of La Réunion, La Réunion, France. PARTICIPANTS: Consecutive patients on ECMO with positive polymerase chain reaction for influenza. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: One hundred twenty-seven consecutive patients were hospitalized in the ICU with a positive influenza polymerase chain reaction from January 2013 to December 2017. Twenty-four influenza patients underwent ECMO including 18 patients with VV-ECMO. During this period, 72 patients requiring VV-ECMO were hospitalized in the ICU. The overall mortality rate of influenza patients on VV-ECMO was 61% versus 46% for non-influenza patients. The standardized mortality ratio per quartile of RESP Score was 1.28 (95% confidence interval 0.61-2.35). CONCLUSIONS: In Reunion, the mortality of patients undergoing VV-ECMO for severe influenza is not lower than the expected mortality of all patients undergoing VV-ECMO.

A constitutive BCL2 down-regulation aggravates the phenotype of PKD1-mutant-induced polycystic kidney disease.

The main identified function of BCL2 protein is to prevent cell death by apoptosis. Mouse knock-out for Bcl2 demonstrates growth retardation, severe polycystic kidney disease (PKD), grey hair and lymphopenia, and die prematurely after birth. Here, we report a 40-year-old male referred to for abdominal and thoracic aortic dissection with associated aortic root aneurysm, PKD, lymphocytopenia with a history of T cell lymphoblastic lymphoma, white hair since the age of 20, and learning difficulties. PKD, which was also detected in the father and sister, was related to an inherited PKD1 mutation. The combination of PKD with grey hair and lymphocytopenia was also reminiscent of Bcl2-/- mouse phenotype. BCL2 gene transcript and protein level were observed to be dramatically decreased in patient peripheral blood T-cells and in his aorta vascular wall cells, which was not detected in parents and sister T-cells, suggesting an autosomal recessive inheritance. Accordingly, spontaneous apoptosis of patient T-cells was increased and could be rescued through stimulation with an anti-CD3 antibody. Direct sequencing of BCL2 gene exons, promoter and 3'UTR region as well as BCL2 mRNA sequencing failed in identifying any pathogenic variant. Array-CGH was also normal and whole exome sequencing of the patient, parents and sister DNA did not detect any significant variant in genes encoding BCL2-interacting proteins. miRNA array identified an up-regulation of miR-181a, which is a known regulator of BCL2 expression. Altogether, miR-181a-mediated decrease in BCL2 gene expression could be a modifying factor that aggravates the phenotype of a PKD1 constitutive variant.

The monocytosis during human leptospirosis is associated with modest immune cell activation states.

Leptospirosis is a life-threatening zoonotic disease and it has been hypothesized that the innate immune system fails to control the infection through ill-characterized mechanisms. The aim of this observational study was to better evaluate the activation processes of monocytes at the early stage of the disease. Blood samples were taken from healthy donors (n = 37) and patients hospitalized for either non-severe (n = 25) or severe (n = 32) leptospirosis. Monocyte cell counts and phenotypes were assessed by flow cytometry. We analysed the expression of several cell activation markers: CD14, CD16, HLA-DR, CD69, TLR2, TLR4, CD11b and CD11c. Although monocyte values at admittance were not significantly different from controls, patients experienced significant monocytosis at 1.33 × 109/L (p < 0.0001 compared to controls: 0.56 × 109/L) during their hospital stay. This monocytosis observed during hospital stay was correlated to several surrogate markers of organ injury. Non-classical (CD14-CD16+) and intermediate (CD14+CD16+) monocyte subsets increased compared to controls (p < 0.05). Accordingly, classical monocyte subset (CD14+CD16-) showed decreased percentages (p < 0.0001). Levels of several cell surface activation molecules were decreased: HLA-DR involved in MHC class II antigen presentation, integrins CD11b and CD11c implicated in phagocytosis and cell recruitment (p < 0.0001). None of these parameters had a prognostic value. Results from this study showed that during acute human leptospirosis, patients experienced monocytosis with a switch toward an inflammation-related phenotype contrasted by low expression levels of markers implicated in monocyte function.

Leptospirosis in ICU: A Retrospective Study of 134 Consecutive Admissions.

OBJECTIVES: Leptospirosis causes reversible multiple organ failure, and its mortality remains high. The aim of this study was to determine the mortality rate of leptospirosis in an ICU offering all types of organ support available nowadays and to compare it with mortality in bacterial sepsis. DESIGN: Retrospective, descriptive, and single-center cohort study. SETTINGS: The largest ICU of Reunion Island (Indian Ocean) in a teaching hospital. PATIENTS: Consecutive patients hospitalized in ICU for leptospirosis from January 2004 to January 2015. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We report 134 cases of patients with leptospirosis hospitalized in ICU. The median age was 40 years (interquartile range, 30-52 yr), with a Simplified Acute Physiology Score II of 38 (27-50) and a Sequential Organ Failure Assessment score of 10 (8-12). Forty-one patients (31%) required mechanical ventilation and 76 (56%) required renal replacement therapy. The door-to-renal replacement therapy time was 0 (0-1) day after admission with a median urea of 25 mmol/L (17-32 mmol/L). Five patients required extracorporeal membrane oxygenation. The mortality rate was 6.0% (95% CI, 2.6-11.4). Among patients hospitalized for sepsis, the standardized mortality ratio of patients with leptospirosis with regards to Simplified Acute Physiology Score II was dramatically low: 0.40 (95% CI, 0.17 - 0.79). CONCLUSIONS: The mortality of severe leptospirosis is lower than for other bacterial infection, provided modern resuscitation techniques are available. Prompt organ support ensures very low mortality rates despite high severity scores.

A major impact of the influenza seasonal epidemic on intensive care units, Réunion, April to August 2016.

The 2016 seasonal influenza in Réunion in the southern hemisphere, was dominated by influenza A(H1N1)pdm09 (possibly genogroup 6B.1). An estimated 100,500 patients with acute respiratory infection (ARI) consulted a physician (cumulative attack rate 11.9%). Sixty-six laboratory-confirmed cases (65.7/100,000 ARI consultations) were hospitalised in an intensive care unit, the highest number since 2009. Impact on intensive care units was major. Correlation between severe cases was 0.83 between Réunion and France and good for 2009 to 2015.

Réunion Island prepared for possible Zika virus emergence, 2016.

Zika virus (ZIKV) has recently spread widely and turned into a major international public health threat. Réunion appears to offer conditions particularly favourable to its emergence and therefore prepared to face possible introduction of the virus. We designed a scaled surveillance and response system with specific objectives, methods and measures for various epidemiological phases including a potential epidemic. Several tools were developed in order to (i) detect individual cases (including a large information campaign on the disease and suspicion criteria), (ii) monitor an outbreak through several complementary systems allowing to monitor trends in disease occurrence and geographic spread and (iii) detect severe forms of the disease in collaboration with hospital clinicians. We put the emphasis on detecting the first cases in order to contain the spread of the virus as much as possible and try to avoid progress towards an epidemic. Our two main strengths are a powerful vector control team, and a close collaboration between clinicians, virologists, epidemiologists, entomologists and public health authorities. Our planned surveillance system could be relevant to Europe and island settings threatened by Zika virus all over the world.

Prevalence and Risk Factors of Stress Cardiomyopathy After Convulsive Status Epilepticus in ICU Patients.

OBJECTIVE: Although stress cardiomyopathy has been described in association with epilepsy, its frequency in patients with convulsive status epilepticus remains unknown. Accordingly, we sought to determine the prevalence and risk factors of stress cardiomyopathy in patients admitted to the ICU for convulsive status epilepticus. DESIGN: Prospective, descriptive, single-center study. SETTING: Medical-surgical ICU of a teaching hospital. PATIENTS: Thirty-two consecutive ventilated patients (21 men; age, 50 ± 18 yr; Simplified Acute Physiology Score II, 53 ± 15; Sequential Organ Failure Assessment, 6 ± 2) hospitalized in the ICU for convulsive status epilepticus. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Hemodynamic parameters, transthoracic echocardiography, biological data, and electrocardiogram were obtained serially on ICU admission (H0), and after 6, 12, 24, and 48 hours of hospitalization (H6, H12, H24, and H48). Stress cardiomyopathy was defined as a 20% decrease in left ventricular ejection fraction between H0 or H6 and H48. Stress cardiomyopathy was diagnosed in 18 patients (56%; 95% CI, 38-74%). Mean left ventricular ejection fraction, left ventricular stroke index and cardiac index were initially (at H0 or H6 according to lowest individual values) significantly reduced in stress cardiomyopathy patients (45 ± 14% vs 61 ± 6%, p < 0.001; 24 ± 8 vs 28 ± 8 mL/m(2), p < 0.05; 2.3 ± 0.7 vs 3.0 ± 0.8 L/min/m(2), p < 0.05, respectively) and increased secondarily to reach similar mean values than those observed in patients without transient left ventricular dysfunction at H24. Dobutamine was more frequently used in patients with stress cardiomyopathy. Mean lactate level was increased and significantly higher in stress cardiomyopathy patients at H0 and H6, whereas mean central venous oxygen saturation was preserved but significantly lower in this group. Only three patients with stress cardiomyopathy had left ventricular regional wall motion abnormalities but normal coronary angiography. Risk factors of stress cardiomyopathy were age and Simplified Acute Physiology Score II. CONCLUSIONS: These results suggest that stress cardiomyopathy is common in patients admitted to the ICU for convulsive status epilepticus. Accordingly, these patients should be screened for stress cardiomyopathy and monitored if they present with hemodynamic compromise.

Impact of Hypertension on Left Ventricular Geometry and Diastolic Function in Africa: Results from the Population-Based TAnve Health (TAHES) Cohort Study.

High blood pressure leads to morphologic changes and functional alterations of the myocardial structure. Transthoracic echocardiography is of great clinical interest to evaluate these alterations, using reference values proposed by the American Society of Echocardiography/European Association of Cardiovascular Imaging, largely based on studies in Caucasian Whites. We aimed to assess the impact of hypertension on echocardiographic parameters in a sub-Saharan African community, using ethnic-specific reference values. This study is part of the TAnve HEalth Study, a population-based prospective cohort study initiated in 2015 in the district of Tanve, Republic of Benin. Hypertension was defined as systolic blood pressure ≥140 mm Hg and/or diastolic blood pressure ≥90 mm Hg and/or currently taking antihypertensive medications. All participants had a transthoracic echocardiography. The patterns of diastolic dysfunction and left ventricular (LV) geometry were defined from 486 subjects in the cohort, free from cardiovascular disease, diabetes, and hypertension. Of all participants, 318 (65% women, median age 48 years) had hypertension. Systolic blood pressure correlated significantly (p <0.0001) with LV mass (r = 0.28), wall thickness (r = 0.25), isovolumic relaxation time (r = 0.27), E/A ratio (r = -0.35), lateral e' velocity (r= -0.41), and E/E' ratio (r = 0.39). Ventricular geometry was normal in only 22% of participants with hypertension when using the American Society of Echocardiography/European Association of Cardiovascular Imaging reference values, versus 69% with ethnic-specific reference ranges. The severity of hypertension was associated with ventricular geometry abnormalities. The prevalence of diastolic dysfunction was 14.5% (confidence interval 10.6% to 18.4%), including relaxation impairment (9%) and pseudonormal pattern (6%). Thus, correct assessment of the repercussions of hypertension on LV geometry in Black Africans requires ethnic-specific reference values.

Mono- and Bi-specific Nanobodies Targeting the CUB Domains of PCPE-1 Reduce the Proteolytic Processing of Fibrillar Procollagens.

The excessive deposition of fibrillar collagens is a hallmark of fibrosis. Collagen fibril formation requires proteolytic maturations by Procollagen N- and C-proteinases (PNPs and PCPs) to remove the N- and C-propeptides which maintain procollagens in the soluble form. Procollagen C-Proteinase Enhancer-1 (PCPE-1, a glycoprotein composed of two CUB domains and one NTR domain) is a regulatory protein that activates the C-terminal processing of procollagens by the main PCPs. It is often up-regulated in fibrotic diseases and represents a promising target for the development of novel anti-fibrotic strategies. Here, our objective was to develop the first antagonists of PCPE-1, based on the nanobody scaffold. Using both an in vivo selection through the immunization of a llama and an in vitro selection with a synthetic library, we generated 18 nanobodies directed against the CUB domains of PCPE1, which carry its enhancing activity. Among them, I5 from the immune library and H4 from the synthetic library have a high affinity for PCPE-1 and inhibit its interaction with procollagens. The crystal structure of the complex formed by PCPE-1, H4 and I5 showed that they have distinct epitopes and enabled the design of a biparatopic fusion, the diabody diab-D1. Diab-D1 has a sub-nanomolar affinity for PCPE-1 and is a potent antagonist of its activity, preventing the stimulation of procollagen cleavage in vitro. Moreover, Diab-D1 is also effective in reducing the proteolytic maturation of procollagen I in cultures of human dermal fibroblasts and hence holds great promise as a tool to modulate collagen deposition in fibrotic conditions.

Non-invasive assessment of left ventricular contractility by myocardial work index in veno-arterial membrane oxygenation patients: rationale and design of the MIX-ECMO multicentre observational study.

Introduction and aims: Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) is an increasingly utilized therapeutic choice in patients with cardiogenic shock, however, high complication rate often counteracts with its beneficial cardiopulmonary effects. The assessment of left ventricular (LV) function in key in the management of this population, however, the most commonly used measures of LV performance are substantially load-dependent. Non-invasive myocardial work is a novel LV functional measure which may overcome this limitation and estimate LV function independent of the significantly altered loading conditions of VA-ECMO therapy. The Usefulness of Myocardial Work IndeX in ExtraCorporeal Membrane Oxygenation Patients (MIX-ECMO) study aims to examine the prognostic role of non-invasive myocardial work in VA-ECMO-supported patients. Methods: The MIX-ECMO is a multicentric, prospective, observational study. We aim to enroll 110 patients 48-72 h after the initiation of VA-ECMO support. The patients will undergo a detailed echocardiographic examination and a central echocardiography core laboratory will quantify conventional LV functional measures and non-invasive myocardial work parameters. The primary endpoint will be failure to wean at 30 days as a composite of cardiovascular mortality, need for long-term mechanical circulatory support or heart transplantation at 30 days, and besides that other secondary objectives will also be investigated. Detailed clinical data will also be collected to compare LV functional measures to parameters with established prognostic role and also to the Survival After Veno-arterial-ECMO (SAVE) score. Conclusions: The MIX-ECMO study will be the first to determine if non-invasive myocardial work has added prognostic value in patients receiving VA-ECMO support.

Normal reference values of cardiac chamber sizes and functional parameters in a beninese community population: the TAHES study.

Reported ranges of normal values for echocardiographic measurements are mostly issued from studies performed in Caucasians. This study is a part of TAHES, a population-based prospective cohort study in Benin and aims to establish normal reference values for echocardiographic cardiac chambers dimensions and Doppler parameters in a Sub-Saharan African population. We included 486 healthy (non-diabetic, non-obese and normotensive) individuals (202 men and 284 women, age 37[30-47] years, BSA 1.58 (1.47-1.67) m2). End-diastolic interventricular septal wall thickness, left ventricular (LV) internal diameter, posterior wall thicknesses, and systolic LV internal diameter were respectively at 10[9-12], 45[43-49], 9[8-11], 29[26-34] mm for male and 9[7-10], 43[41-46], 8[7-], 29[27-32] mm for females. LV mass was significantly greater in males even after normalization for the body surface area (98[85-117] vs. 82[71-96] g/m2). Upper limits of BSA-indexed LV mass were 145 g/m2 for males and 124 g/m2 for females. The allometric exponent that described the LV mass-Height relationship were 2.5 in both sexes but 1.2 for males and 1.8 for females separately. E-wave velocity was 0.79 [0.65-0.90] cm/sec in males and 0.88 [0.78-0.99]cm/sec in females (p < 0.0001) but without significant gender differences in E/A ratio (limits: 0.75 and 2.1). The e'-wave velocity (lower limit = 8 cm/sec) decreased and E/e' ratio (Upper limit = 9) increased with aging. Upper limit of BSA-indexed left atrium volume was 38 mL/m2 for both sexes. In conclusion, normal values from a general population in West Africa differ from those established in Caucasian populations with greater LV mass and wall thicknesses.

Predicting factors for the need of extracorporeal membrane oxygenation for suicide attempts by cardiac medication: a single-center cohort study.

BACKGROUND: Severe poisoning due to the overdosing of cardiac drugs can lead to cardiovascular failure. In order to decrease the mortality rate, the most severe patients should be transferred as quickly as possible to an extracorporeal membrane oxygenation (ECMO) center. However, the predictive factors showing the need for venous-arterial ECMO (VA-ECMO) had never been evaluated. METHODS: A retrospective, descriptive, and single-center cohort study. All consecutive patients admitted in the largest ICU of Reunion Island (Indian Ocean) between January 2013 and September 2018 for beta-blockers (BB), calcium channel blockers (CCB), renin-angiotensin-aldosterone system blockers, digoxin or anti-arrythmic intentional poisonings were included. ECMO implementation was the primary outcome. RESULTS: A total of 49 consecutive admissions were included. Ten patients had ECMO, 39 patients did not have ECMO. Three patients in ECMO group died, while no patients in the conventional group died. The most relevant ECMO-associated factors were pulse pressure and heart rate at first medical contact and pulse pressure, heart rate, arterial lactate concentration, liver enzymes and left ventricular ejection fraction (LVEF) at ICU-admission. Only pulse pressure at first medical contact and LVEF were significant after logistic regression. CONCLUSION: A transfer to an ECMO center should be considered for a pulse pressure < 35 mmHg at first medical contact or LVEF < 20% on admission to ICU.

Titanate nanoribbon-based nanobiohybrid for potential applications in regenerative medicine.

Nanoparticles capable of mimicking natural tissues represent a major technological advancement in regenerative medicine. In this pilot study, the development of a new nanohybrid composed of titanate nanoribbons to mimic the extracellular matrix is reported. During the first phase, nanoribbons were synthesized by hydrothermal treatment. Subsequently, titanate nanoribbons were functionalized by heterobifunctional polyethylene-glycol (PEG) to graft type I collagen on their surface. Biological properties of this new nanobiohybrid such as cytotoxicity to cardiac cells and platelet aggregation ability were evaluated. The so-formed nanobiohybrid permits cellular adhesion and proliferation favoring fine cardiac tissue healing and regeneration.

Severe community-acquired pneumonia in Reunion Island: Epidemiological, clinical, and microbiological characteristics, 2016-2018.

PURPOSE: No data are available on severe community-acquired pneumonia (CAP) in the French overseas department of Reunion Island. This is unfortunate as the microorganisms responsible for the disease are likely to differ from those in temperate regions due to a tropical climate and proximity to other islands of the Indian Ocean region. The aim of this study was to assess the epidemiological, clinical, prognosis, and microbiological characteristics of patients with severe CAP in Reunion Island. MATERIALS AND METHODS: This retrospective study evaluated all patients with CAP aged >18 years and hospitalized in one of the two intensive care units of Reunion Island between 2016 and 2018. Microorganisms were identified by culture from blood and respiratory samples, multiplex polymerase chain reaction from respiratory samples, urinary antigen tests, and serology. RESULTS: Over the study period, 573 cases of severe CAP were recorded, with a mean incidence of 22 per 100,000 person-years. The most frequently isolated microorganism was influenza (21.9%) followed by Streptococcus pneumoniae (12%). The influenza virus was detected in affected patients all year round. Twenty-four patients with severe CAP came from another island of the Indian Ocean region (4.2%), mainly Madagascar (>50%). Two of these patients presented with melioidosis and 4 were infected with Acinetobacter spp. CONCLUSIONS: Our findings have major implications for the management of severe CAP in tropical regions. The most frequently isolated microorganism in patients with severe CAP in Reunion Island is influenza followed by S. pneumoniae. Physicians should be aware that influenza is the main cause of severe CAP in patients living in or returning from Reunion Island, where this virus circulates all year round.

Plasma phospholipid transfer protein deficiency in mice is associated with a reduced thrombotic response to acute intravascular oxidative stress.

OBJECTIVE: Earlier in vitro studies suggested a putative role for the plasma phospholipid transfer protein (PLTP) in the modulation of blood coagulation. The effect of PLTP expression on blood coagulation under both basal and oxidative stress conditions was compared here in wild-type and PLTP-deficient (PLTP-/-) mice. METHODS AND RESULTS: Under basal conditions, PLTP deficiency was associated with an extended tail bleeding time despite a significant depletion of vascular α-tocopherol content and an impairment of endothelial function. When acute oxidative stress was generated in vivo in the brain vasculature, the steady state levels of oxidized lipid derivatives, the extent of blood vessel occlusion, and the volume of ischemic lesions were more severe in wild-type than in PLTP-/- mice. CONCLUSIONS: In addition to its recognized hyperlipidemic, proinflammatory, and proatherogenic properties, PLTP increases blood coagulation and worsens the extent of ischemic lesions in response to acute oxidative stress. Thus, PLTP arises here as a cardiovascular risk factor for the late thrombotic events occurring in the acute phase of atherosclerosis.