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Background: The exercise pressor reflex, i.e., metabo- and mechano-reflex, partially regulates the control of ventilation and cardiovascular function during exercise. Abnormal exercise pressor reflex response has been associated with exaggerated ventilatory drive, sympathovagal imbalance and exercise limitation in chronic heart failure patients. Whether metaboreflex is over-activated and participate to poor aerobic capacity in patients with hereditary transthyretin cardiac amyloidosis (CA-TTR) is unknown.Methods: Twenty-two CA-TTR patients (aged 76 ± 7, 68% male) with the V122I (p.Val142Ile) transthyretin underwent a thorough evaluation including heart rate variability metrics, electrochemical skin conductance (ESC), physical function cardiopulmonary exercise testing, and muscle metaboreflex assessment. Eleven control subjects were chosen for muscle metaboreflex assessment.Results: Age-matched controls (n = 11) and CA-TTR patients (n = 22) had similar metaboreflex sensitivity for heart rate, stroke volume, cardiac index and mean systemic arterial pressure. Compared with age-matched controls, metaboreflex sensitivity for systemic vascular resistance (−18.64% ± 6.91% vs 3.14% ± 23.35%) and minute-ventilation responses (−9.65% ± 14.83% vs 11.84% ± 23.1%) was markedly increased in CA-TTR patients. Values of ESC displayed positive correlations with stroke volume (r = 0.53, p = 0.011) and cardiac index (r = 0.51, p = 0.015) components of metaboreflex sensitivity, an inverse correlation with systemic vascular resistance (r = −0.55, p = 0.008) and a trend with mean arterial (r = −0.42, p = 0.052) components of metaboreflex sensitivity. Peak aerobic capacity (peak VO2%) displayed an inverse correlation with the ventilation component of metaboreflex sensitivity (r = −0.62, p = 0.015).Conclusion: Consistent with the “muscle hypothesis” in heart failure, it is proposed that deterioration of skeletal muscle function in hereditary CA-TTR patients may activate muscle metaboreflex, leading to an increase in ventilation and sensation of breathlessness, the perception of fatigue, and overall sympathetic activation.

Objective: The objective of this study was to determine the incidence of early air transport (EAT) morbidity after transpleural surgery. We compared our cohort with our patients not requiring air transport. Methods: This was a retrospective observational study, in the Thoracic and Cardiovascular Surgery Department of the University Hospital of Martinique over 40 months. We included all of the files (national and local database, and systematic postoperative consultation) of patients operated on for thoracic surgery or distinguished transpleural surgical intervention, whatever their geographical origin. Patients from another French department benefited from EAT. The complications were classified according to Clavien–Dindo before or after the EAT. Diagnostic criteria were chest pain, dyspnea, and abnormal chest radiograph. Continuous variables are presented as mean, median, and SDs. Discrete variables are presented as n (%). Results: Of 491 patients operated on, 315 were transpleural surgeries, and 99 patients benefited from EAT. There were 55% resections, a percent predicted of forced expiratory volume in 1 second, and an average preoperative Tiffeneau ratio of respectively, 86% and 78. One complication was found: a pneumothorax in an emphysematous patient, 15 days after the flight, who had an index of prolonged air leak >10. The mean time between surgery and flight was 7.2 days (σ = 4.5), and 3.3 days (σ = 2.9) between removal of the last drain and flight. The morbidity of EAT after transpleural surgery was 1%. The 2 cohorts of “EAT” and “Locals” patients were statistically comparable, particularly in morbidity. Conclusions: EAT appears to be safe after transpleural surgery, following usual criteria for hospital discharge. It would be interesting to study, on a larger scale, the effect of IPAL as an independent risk factor (in case of high IPAL > 10) as well as pathologies that modify transpleural pressures restrictive ventilatory defect.

Abstract Background Pulmonary involvement in individuals with transthyretin cardiac amyloidosis is unclear. The aim of this study was to quantify 99mTc-hydroxy methylene diphosphonate (HMDP) lung retention in hereditary transthyretin (ATTRv) cardiac amyloidosis patients and to relate tracer uptake intensity to pulmonary function and aerobic capacity. Methods We prospectively enrolled 20 patients with biopsy-proven ATTRv cardiac amyloidosis and 20 control subjects. Cardiac involvement was confirmed by echocardiography and nuclear imaging using 99mTc-HMDP. Semi-quantitative analysis of the heart, rib and lung retention was assessed using a simple region of interest technique. Pulmonary function was evaluation by the means of whole-body plethysmography, diffusing capacity of the lung for carbon monoxide, forced oscillation technique and cardiopulmonary exercise testing. Results Pulmonary tracer uptake estimated by lung to rib retention ratio was higher in ATTRv amyloidosis patients compared with control subjects: median 0.62 (0.55–0.69) vs 0.51 (0.46–0.60); p = 0.014. Analysis of relation between lung 99mTc-HMDP retention and pulmonary function parameters shown statistically significant correlations with total lung volume (% predicted), lung reactance (Xrs 5 Hz) and peak VO2, suggesting total lung capacity restriction impaired elastic properties of the lung and poor aerobic capacity. Conclusion Our study suggests that some grade of pulmonary retention of 99mTc-HMDP may occur in patients with cardiac ATTRv amyloidosis, which can elicit deleterious effects on patient’s lung function and aerobic capacity.

Snakebite envenomation is a relevant medical hazard in French Guiana and Martinique, two French territories in the Americas. All snakebite envenomations in Martinique are inflicted by the endemic viperid species Bothrops lanceolatus, whereas Bothrops atrox is responsible for the majority of snakebites in French Guiana, although other venomous snake species also occur in this South American territory. This review summarizes some of the key aspects of the natural history of these species, as well as of their venom composition, the main clinical manifestations of envenomations, and their treatment by antivenoms. B. atrox venom induces the typical set of clinical manifestations characteristic of Bothrops sp. venoms, i.e., local tissue damage and systemic alterations associated with coagulopathies, hemorrhage, hemodynamic alterations, and acute kidney injury. In the case of B. lanceolatus venom, in addition to some typical features of bothropic envenomation, a unique and severe thrombotic effect occurs in some patients. The pathogenesis of this effect remains unknown but may be related to the action of venom components and inflammatory mediators on endothelial cells in the vasculature. A monospecific antivenom has been successfully used in Martinique to treat envenomations by B. lanceolatus. In the case of French Guiana, a polyvalent antivenom has been used for some years, but it is necessary to assess the preclinical and clinical efficacy against viperid venoms in this country of other antivenoms manufactured in the Americas.

Background and objective: Along with impaired aerobic capacity, increased slope of the relationship between ventilation (VE) and pulmonary CO2 output (VCO2), i.e., VE-VCO2 slope is a common finding in patients with cardiac amyloidosis (CA), which suggests ventilatory inefficiency. Little is known about mechanisms leading to ventilatory inefficiency in CA patients. The purpose of this investigation was to examine the factors that underlie the abnormal ventilatory efficiency in transthyretin hereditary CA patients, such as excessive ventilatory drive, inability of pulmonary blood flow to increase adequately during exercise and excessive sympathetic stimulation, which are known mechanisms of VE-VCO2 slope increase.Methods: In this single-center retrospective observational study, consecutive patients (n = 41) with known familial transthyretin amyloidosis p.Val142Ile mutation carriers with confirmed cardiac phenotype were included.Results: Compared with CA patients without ventilatory inefficiency (VE-VCO2 slope < 36), patients with ventilatory inefficiency (VE-VCO2 slope ≥ 36) had increased inter-ventricular septum thickness, lower VO2 peak along with hyperventilation, and prolonged post-exercise heart rate recovery. By multivariate analysis, only excess of minute-ventilation at anaerobic threshold (β = 0.127; p = 0.011) remained an independent predictor of ventilatory inefficiency.Conclusion: Our data suggest that high ventilatory stimulation during exercise leading to hyperventilation is the main determinant of ventilatory inefficiency in hereditary transthyretin cardiac amyloidosis patients. This novel finding helps to better understand the mechanism of exercise intolerance in these patients where physiological limitation may be related to both heart dysfunction and abnormal pulmonary response.

IntroductionEnvenomations by Bothrops snakebites can induce overwhelming systemic inflammation ultimately leading to multiple organ system failure and death. Release of damage-associated molecular pattern molecules (DAMPs), in particular of mitochondrial origin, has been implicated in the pathophysiology of the deregulated innate immune response.ObjectiveTo test whether whole Bothrops lanceolatus venom would induce mitochondrial dysfunction and DAMPs release in human heart preparations.MethodsHuman atrial trabeculae were obtained during cannulation for cardiopulmonary bypass from patients who were undergoing routine coronary artery bypass surgery. Cardiac fibers were incubated with vehicle and whole Bothrops lanceolatus venom for 24hr before high-resolution respirometry, mitochondrial membrane permeability evaluation and quantification of mitochondrial DNA.ResultsCompared with vehicle, incubation of human cardiac muscle with whole Bothrops lanceolatus venom for 24hr impaired respiratory control ratio and mitochondrial membrane permeability. Levels of mitochondrial DNA increased in the medium of cardiac cell preparation incubated with venom of Bothrops lanceolatus.ConclusionOur study suggests that whole venom of Bothrops lanceolatus impairs mitochondrial oxidative phosphorylation capacity and increases mitochondrial membrane permeability. Cardiac mitochondrial dysfunction associated with mitochondrial DAMPs release may alter myocardium function and engage the innate immune response, which may both participate to the cardiotoxicity occurring in patients with severe envenomation.

Cardiac amyloidosis (CA) is a myocardial disease characterized by extracellular amyloid infiltration throughout the heart, resulting in increased myocardial stiffness, and restrictive heart wall chamber behavior. Its diagnosis among patients hospitalized for cardiovascular diseases is becoming increasingly frequent, suggesting improved disease awareness, and higher diagnostic capacities. One predominant functional manifestation of patients with CA is exercise intolerance, objectified by reduced peak oxygen uptake (VO2 peak), and assessed by metabolic cart during cardiopulmonary exercise testing (CPET). Hemodynamic adaptation to exercise in patients with CA is characterized by low myocardial contractile reserve and impaired myocardial efficiency. Rapid shallow breathing and hyperventilation, in the absence of ventilatory limitation, are also typically observed in response to exercise. Ventilatory inefficiency is further suggested by an increased VE-VCO2 slope, which has been attributed to excessive sympathoexcitation and a high physiological dead space (VD/VT) ratio during exercise. Growing evidence now suggests that, in addition to well-established biomarker risk models, a reduced VO2 peak is potentially a strong and independent predictive factor of adverse patient outcomes, both for monoclonal immunoglobulin light chain (AL) or transthyretin (ATTR) CA. Besides generating prognostic information, CPET can be used for the evaluation of the impact of therapeutic interventions in patients with CA.

AimThe link between transthyretin cardiac amyloidosis (CATTR), and cerebral ischemic events (CIE) has only been hinted at till now, impeding progress in patient management. We seek to evaluate the frequency and characteristics of CIE in Afro-Caribbean patients followed for CATTR at our institution.MethodsIn this single-center retrospective observational study, Afro-Caribbean patients followed for CATTR between July 2005 and October 2019 were included. Occurrence of CIE was investigated, and their cardioembolic origin determined. Analysis of patient characteristics was conducted according to CIE and CATTR profiles.ResultsOverall, 120 CATTR patients were included: 17 wild-type ATTR (14.2%), 73 ATTR-V122I (60.8%), and 22 ATTR-I107V (18.3%). Thirty-six patients (30.0%) presented with CIE, including three transient ischemic attacks and 33 permanent ischemic strokes (75.8% with a cardioembolic pattern). CIE was concomitant with CATTR diagnosis in 16 (16/36: 44.4%) patients, while 14 patients (14/36: 38.9 %) experienced CIE over a median CATTR follow-up of 2.0 years (min-max range: 0.8–4.4 years). CATTR-CIE patients presented with atrial fibrillation (66.7%), left atrial enlargement (77.8%), a CHA2DS2-VASc ≥ 3 (97.2%) and a high anticoagulant intake (75.0%). Multivariate analysis retained only a high CHA2DS2-VASc score as an independent predictor of CIE risk (Hazard Ratio [95% CI]: 12.03 [1.62–89.24]).ConclusionConcomitant CIE, and CATTR diagnosis, potentially carries a worse prognosis. A CHA2DS2-VASc score ≥3 seems to be a strong and independent predictive factor of CIE in CATTR patients. Further studies are needed to assess the efficacy and timeliness of anticoagulation in CATTR patients, independently of atrial fibrillation.

Abstract Background Von Willebrand disease was diagnosed in two Afro‐Caribbean patients and sequencing of the VWF gene (VWF) revealed the presence of multiple variants located throughout the gene, including variants located in the D4 domain of VWF: p.(Pro2145Thrfs*5) in one patient and p.(Cys2216Phefs*9) in the other patient. Interestingly, D4 variants have not been studied often. Objectives Our goal was to characterize how the D4 variants p.(Pro2145Thrfs*5) and p.(Cys2216Phefs*9) influenced VWF biosynthesis/secretion and functions using in vitro assays. Methods Recombinant VWF (rVWF), mutant or wild‐type, was produced via transient transfection of the human embryonic kidney cell line 293T. The use of different tags for the wild‐type and the mutant allele allowed us to distinguish between the two forms when measuring VWF antigen in medium and cell lysates. Binding of rVWF to its ligands, collagen, factor VIII, ADAMTS13, and platelet receptors was also investigated. Results Homozygous expression of the p.(Cys2216Phefs*9)‐rVWF mutation resulted in an almost complete intracellular retention of the protein. Heterozygous expression led to secretion of almost exclusively wild‐type‐rVWF, logically capable of normal interaction with the different ligands. In contrast, the p.(Pro2145Thrfs*5)‐rVWF exhibited reduced binding to type III collagen and αIIbβ3 integrin compared to wild‐type‐rVWF. Conclusions We report two mutations of the D4 domains that induced combined qualitative and quantitative defects.

Wound healing is a well-tuned biological process, which is achieved via consecutive and overlapping phases including hemostasis, inflammatory-related events, cell proliferation and tissue remodeling. Several factors can impair wound healing such as oxygenation defects, aging, and stress as well as deleterious health conditions such as infection, diabetes, alcohol overuse, smoking and impaired nutritional status. Growing evidence suggests that reactive oxygen species (ROS) are crucial regulators of several phases of healing processes. ROS are centrally involved in all wound healing processes as low concentrations of ROS generation are required for the fight against invading microorganisms and cell survival signaling. Excessive production of ROS or impaired ROS detoxification causes oxidative damage, which is the main cause of non-healing chronic wounds. In this context, experimental and clinical studies have revealed that antioxidant and anti-inflammatory strategies have proven beneficial in the non-healing state. Among available antioxidant strategies, treatments using mitochondrial-targeted antioxidants are of particular interest. Specifically, mitochondrial-targeted peptides such as elamipretide have the potential to mitigate mitochondrial dysfunction and aberrant inflammatory response through activation of nucleotide-binding oligomerization domain (NOD)-like family receptors, such as the pyrin domain containing 3 (NLRP3) inflammasome, nuclear factor-kappa B (NF-κB) signaling pathway inhibition, and nuclear factor (erythroid-derived 2)-like 2 (Nrf2).

AimsDevelopment of metabolic syndrome is associated with impaired cardiac performance, mitochondrial dysfunction and pro-inflammatory cytokine increase, such as the macrophage migration inhibitory factor MIF. Depending on conditions, MIF may exert both beneficial and deleterious effects on the myocardium. Therefore, we tested whether pharmacological inhibition of MIF prevented or worsened metabolic syndrome-induced myocardial dysfunction.Methods and resultsC57BL/6J mice were fed for ten weeks with 60% fat-enriched diet (HFD) or normal diet (ND). MIF inhibition was obtained by injecting mice twice a week with ISO-1, for three consecutive weeks. Then, triglycerides, cholesterol, fat mass, glucose intolerance, insulin resistance, ex vivo cardiac contractility, animal energetic substrate utilization assessed by indirect calorimetry and mitochondrial respiration and biogenesis were evaluated. HFD led to fat mass increase, dyslipidemia, glucose intolerance and insulin resistance. ISO-1 did not alter these parameters. However, MIF inhibition was responsible for HFD-induced cardiac dysfunction worsening. Mouse capacity to increase oxygen consumption in response to exercise was reduced in HFD compared to ND, and further diminished in ISO-1-treated HFD group. Mitochondrial respiration was reduced in HFD mice, treated or not with ISO-1. Compared to ND, mitochondrial biogenesis signaling was upregulated in the HFD as demonstrated by mitochondrial DNA amount and PGC-1α expression. However, this increase in biogenesis was blocked by ISO-1 treatment.ConclusionMIF inhibition achieved by ISO-1 was responsible for a reduction in HFD-induced mitochondrial biogenesis signaling that could explain majored cardiac dysfunction observed in HFD mice treated with MIF inhibitor.

Injection of autologous bone marrow cells into infarcted myocardium has been proposed to limit the deterioration of cardiac function following myocardial infarction (MI); unfortunately, the beneficial effects observed have been modest. One of the limiting factors is believed to be poor local survival of the injected cells, but the potential impact of apoptosis among the injected cells has yet to be assessed. Therefore, this study aimed to quantify the apoptosis rate in bone marrow mononuclear cells (BMMCs) prepared for cardiac therapy, and to analyze their effects in vitro on cardiomyoblast apoptosis and in vivo on cardiac function recovery following MI. Using rabbit BMMCs prepared by Ficoll gradient, apoptotic cells were detected via Annexin V (AnV) staining. The effects of depleting the apoptotic cell population by means of AnV magnetic beads was tested in vitro after coculture with cardiomyoblasts (H9c2 cells) and in vivo after cell injection into the infarcted area. Left ventricular ejection fraction and scar extent were assessed by echography and histology 2 months later. After Ficoll gradient isolation, 37.3% (33.4–37.9%) of BMMCs were found to be apoptotic (Apo Base BMMCs). AnV depletion decreased the proportion of apoptotic cells to 20% (17.6–32%) (Apo Low BMMCs). Rabbits treated in vivo with Apo Low BMMCs after MI presented with significantly improved left ventricular ejection fraction [41.4% (41.0–43.6%) vs. 34.6% (34.6–35.9%), p = 0.03), reduced scar extent [20.4% (17.9–24.3%) vs. 25.6% (17.9–27.9%), p = 0.057], and reduced rate of cardiomyocyte apoptosis compared to those treated with Apo Base BMMCs. H9c2 apoptosis was found to be higher after coculture with Apo Base than with Apo Low BMMCs [25.6% (22.6–29.6%) vs. 10.1% (6.6–12.6%), p = 0.03], a result partially reproduced by cocultures with microparticle-rich supernatants from BMMCs. The presence of apoptotic cells among BMMCs impairs the efficacy of cardiac cell therapy after MI, an effect possibly mediated by apoptotic microparticles.

Abstract There are numerous conflicting recommendations available on the use of antibiotics following snakebite. The present letter to the editor presents some recommendations based on recent studies, and aims to stimulate debate on this topic.

Introduction: Out-of-hospital cardiac arrest (OHCA) affects approximately 46,000 people in France annually and survival remains low. There is no published data specific to the characteristics and outcomes of OHCA in French overseas territories, especially in the French Caribbean territories. The aim of this study was to describe the characteristics and outcomes of adult OHCA patients managed by the Emergency Medical Service team (EMS) in Martinique. Methods: All adults with OHCA, managed by the EMS of Martinique between January 1st 2018 and June 30th 2019, were included. Primary outcome was 30 day-survival and neurological outcome at 30 days assessed by the Cerebral Performance Category scale (CPC). Secondary outcomes were return of spontaneous circulation (ROSC) prior to hospital admission and causes of cardiac arrest in patients with ROSC. Results: This study included 340 OHCA patients. The population was predominantly male (64%), with a median age of 68 [54–78] years. OHCA resulted from a medical condition in 314 patients (92%) and occurred mainly at home (75%), in the presence of witnesses for 235 patients (69%). Basic life support was initiated in 174 OHCA (51%). Median time to first-responders’ and prehospital mobile intensive care unit’s arrivals at scene were 17 [10–30] and 27 [19–41] minutes after call to the EMS dispatching center for OHCA. Non-shockable initial rhythm was present in 315 patients (93%), and 240 patients (71%) received advanced life support. Thirty-one patients (9%) achieved ROSC. On day 30, 13 patients (3.8%) were still alive, and 8 of them (2.4%) were alive with a CPC score of 1 or 2. Conclusion: The overall adult OHCA survival rate and survival with good neurological status on day-30 in the French Caribbean island of Martinique are low. OHCA survival rate may be improved by educating the population on basic life support techniques and reducing the time responses for first-responders and prehospital mobile intensive care unit to reach patients.

Bothrops lanceolatus (Bl), a snake endemic to Martinique, is responsible for numerous envenomations annually, leading to severe complications such as thrombosis, necrosis, and hemorrhage. This case series investigates the link between Bothrops lanceolatus envenomation and acute myocarditis, utilizing cardiac magnetic resonance imaging (MRI) to enhance management strategies. In both cases, cardiac MRI confirmed myocarditis with edema, and subsequent cerebral MRI revealed bilateral infarcts. Elevated troponin levels further supported the myocarditis diagnosis. Multiple doses of Bothrofav® antivenom facilitated recovery without clinical after effects.These cases represent the first documented instances of myocarditis due to Bl envenomation confirmed via cardiac MRI. Prompt administration of antivenom and the use of advanced imaging techniques were crucial in achieving favorable outcomes.

Summary This article describes the structures and processes involved in healthcare delivery for sepsis, from the prehospital setting until rehabilitation. Quality improvement initiatives in sepsis may reduce both morbidity and mortality. Positive outcomes are more likely when the following steps are optimized: early recognition, severity assessment, prehospital emergency medical system activation when available, early therapy (antimicrobials and hemodynamic optimization), early orientation to an adequate facility (emergency room, operating theater or intensive care unit), in-hospital organ failure resuscitation associated with source control, and finally a comprehensive rehabilitation program. Such a trajectory of care dedicated to sepsis amounts to a chain of survival and rehabilitation for sepsis. Implementation of this chain of survival and rehabilitation for sepsis requires full interconnection between each link. To date, despite regular international recommendations updates, the adherence to sepsis guidelines remains low leading to a considerable burden of the disease. Developing and optimizing such an integrated network could significantly reduce sepsis related mortality and morbidity.

Background: Consumption coagulopathy and hemorrhagic syndrome are the typical features of Bothrops sp. snake envenoming. In contrast, B. lanceolatus envenoming can induce thrombotic complications. Our aim was to test whether crude B. lanceolatus and B. atrox venoms would display procoagulant activity and induce thrombus formation under flow conditions. Methods and Principal Findings: Fibrin formation in human plasma was observed for B. lanceolatus venom at 250–1000 ng/mL concentrations, which also induced clot formation in purified human fibrinogen, indicating thrombin-like activity. The degradation of fibrinogen confirmed the fibrinogenolytic activity of B. lanceolatus venom. B. lanceolatus venom displayed consistent thrombin-like and kallikrein-like activity increases in plasma conditions. The well-known procoagulant B. atrox venom activated plasmatic coagulation factors in vitro and induced firm thrombus formation under high shear rate conditions. In contrast, B. lanceolatus venom induced the formation of fragile thrombi that could not resist shear stress. Conclusions: Our results suggest that crude B. lanceolatus venom displays amidolytic activity and can activate the coagulation cascade, leading to prothrombin activation. B. lanceolatus venom induces the formation of an unstable thrombus under flow conditions, which can be prevented by the specific monovalent antivenom Bothrofav®.

Bothrofav, a monospecific antivenom, was introduced in June 1991 and has shown excellent effectiveness against life-threatening and thrombotic complications of Bothrops lanceolatus envenoming. Because of the reoccurrence of cerebral stroke events despite the timely administration of antivenom, new batches of Bothrofav were produced and introduced into clinical use in January 2011. This study’s aim was to evaluate the effectiveness of Bothrofav generations at treating B. lanceolatus envenoming. During the first period of the study (2000–2010), 107 patients were treated with vials of antivenom produced in June 1991, while 282 envenomed patients were treated with vials of antivenom produced in January 2011 in the second study period (2011–2023). Despite timely antivenom administration, thrombotic complications reoccurred after an interval free of thrombotic events, and a timeframe analysis suggested that the clinical efficacy of Bothrofav declined after it reached its 10-year shelf-life. In of the case of an antivenom shortage due to the absence of regular batch production, no adverse effects were identified before the antivenom reached its 10-year shelf-life, which is beyond the accepted shelf-life for a liquid-formulation antivenom. While our study does not support the use of expired antivenom for potent, life-threatening B. lanceolatus envenoming, it can be a scientific message to public entities proving the necessity of new antivenom production for B. lanceolatus envenoming.

Objective. To analyze, describe, and quantify the collaborations and scientific output of the two university teaching hospitals of Martinique and Guadeloupe, at the regional, national, and international level. Methods. A bibliometrics analysis was performed from the international databases Web of Science and PubMed, for the period from 1989 to 2018, inclusive (30 years). Three types of bibliometric indicators were used, namely quantitative indicators, performance indicators, and organization-specific indicators. Affiliations of the first and last authors were identified from PubMed. Results. Between 1989 and 2018, a total of 1 522 indexed articles were published with at least one author affiliated to either the University Hospital of Martinique (n = 827) or the University Hospital of Guadeloupe (n = 685). The majority of articles were in category Q1 (35.8% for Martinique and 35.2% for Guadeloupe). In Martinique, over the last 30 years, the three main research areas have been clinical neurology, ophthalmology, and surgery, together representing 28.7% of all research areas, with the highest number of articles published in the field of clinical neurology (n = 81). In the University Hospital of Guadeloupe, the area of hematology was largely represented, with 79 articles published. For both hospitals, the first and last authors of the articles published were mainly from mainland France. Conclusions. This quantitative analysis shows the development of medical and scientific research in Martinique and Guadeloupe over the last three decades, as well as the extent of their collaborative partnerships at the national and international levels.

Consumption coagulopathy and hemorrhagic syndrome exacerbated by blood anticoagulability remain the most important causes of lethality associated with Bothrops snake envenomation. Bothrops venom also engages platelet aggregation on the injured endothelium via von Willebrand factor (vWF) interactions. Besides platelet aggregation, some Bothrops venom toxins may induce qualitative thrombopathy, which has been in part related to the inhibition of vWF activation. We tested whether B. lanceolatus venom impaired vWF to collagen(s) binding (vWF:CB) activity. Experiments were performed with B. lanceolatus crude venom, in the presence or absence of Bothrofav, a monospecific B. lanceolatus antivenom. Venom of B. lanceolatus fully inhibited vWF to collagen type I and III binding, suggesting venom interactions with the vWF A3 domain. In contrast, B. lanceolatus venom increased vWF to collagen type VI binding, suggesting the enhancement of vWF binding to collagen at the vWF A1 domain. Hence, B. lanceolatus venom exhibited contrasting in vitro effects in terms of the adhesive properties of vWF to collagen. On the other hand, the antivenom Bothrofav reversed the inhibitory effects of B. lanceolatus venom on vWF collagen binding activity. In light of the respective distribution of collagen type III and collagen type VI in perivascular connective tissue and the sub-endothelium, a putative association between an increase in vWF:CB activity for collagen type VI and the onset of thrombotic events in human B. lanceolatus envenomation might be considered.

Diabetic wound healing is a global medical challenge. Several studies showed that delayed healing in diabetic patients is multifactorial. Nevertheless, there is evidence that excessive production of ROS and impaired ROS detoxification in diabetes are the main cause of chronic wounds. Indeed, increased ROS promotes the expression and activity of metalloproteinase, resulting in a high proteolytic state in the wound with significant destruction of the extracellular matrix, which leads to a stop in the repair process. In addition, ROS accumulation increases NLRP3 inflammasome activation and macrophage hyperpolarization in the M1 pro-inflammatory phenotype. Oxidative stress increases the activation of NETosis. This leads to an elevated pro-inflammatory state in the wound and prevents the resolution of inflammation, an essential step for wound healing. The use of medicinal plants and natural compounds can improve diabetic wound healing by directly targeting oxidative stress and the transcription factor Nrf2 involved in the antioxidant response or the mechanisms impacted by the elevation of ROS such as NLRP3 inflammasome, the polarization of macrophages, and expression or activation of metalloproteinases. This study of the diabetic pro-healing activity of nine plants found in the Caribbean highlights, more particularly, the role of five polyphenolic compounds. At the end of this review, research perspectives are presented.

Abstract The coronavirus disease (Covid-19) crisis presents as human, social and economic challenges. The advent of Covid-19, unfortunate as it is, has highlighted the need for close medical cooperation between states. Medical cooperation is the key counter to fight against the Covid-19 pandemic.

Snakebite envenoming is a pathological condition which may occur in response to the injection of venom. Snake venoms contain a complex mixture of biologically active molecules which are responsible for a broad spectrum of clinical manifestations, ranging from local tissue injuries to fatal complications. Snake venom administration commonly provokes local tissue injury often associated with systemic effects, including neurotoxic and cardiotoxic manifestations, bleeding, acute kidney injury, and rhabdomyolysis. An important spectrum of pathogenesis of snake envenomation is the generation of reactive oxygen species (ROS), which can directly provoke tissue damage and also potentiate the deleterious consequences of inflammation at the bite site. Snake venom components known to induce oxidative stress include phospholipases A2, metalloproteinases, three-finger toxins, and L-amino acid oxidase. Clear evidence is mounting suggesting that inflammation and oxidative stress participate in the destructive effects of envenoming, including acute renal failure, tissue necrosis, and unusual susceptibility to bleed (hemorrhage), mostly due to hypocoagulability, neuro/cardio toxicity, and myonecrosis. Impaired regulation of oxidative stress may also set the stage for secondary/long-term complications of snakebite envenomation such as musculoskeletal disabilities. Some aspects of natural antioxidant therapeutic options are discussed in this review.

Ciguatera poisoning (CP) is one of the most common causes worldwide of marine poisoning associated with fish consumption from tropical areas. Its incidence is underreported. CP cases seem to increase with grouped cases reported during summer. Exposure to ciguatoxins, toxins responsible for CP with sodium-channel agonistic, voltage-gated potassium channel blocking, cholinergic, and adrenergic activities, may result in a large spectrum of manifestations. We aimed to describe the clinical characteristics, management, and outcome of CP in Martinique, French West Indies. We conducted an observational retrospective single-center study during six years (October 2012 to September 2018) including all CP patients managed by the prehospital medical services, admitted to the university hospital emergency department, or declared to the regional health agency. A total of 149 CP patients (81 females/63 males; median age, 46 years (interquartile range, 34–61)) were included. Acute features consisted in general (91%; mainly, myalgia pruritus, and asthenia), gastrointestinal (90%; mainly diarrhea, abdominal pain, and nausea), neurological (72%; mainly, paresthesia, dysgeusia, and impairment of hot/cold feeling), and cardiovascular manifestations (22%; bradycardia, hypotension, and heart conduction disorders). Management was supportive. No patient died but symptoms persisted in 40% of the 77 patients with follow-up at day 15. CP was mainly attributed to the ingestion of trevallies (59%), snappers (13%), and king mackerels (8%) with collective contaminations (71%). Unusual fish (tuna, salmon, and spider conchs) were suspected in rare cases. Ingestion of trevallies was associated with significantly higher persistent symptoms (odds ratio, 3.00; 95% confidence interval, (1.20–8.00); p = 0.03). CP incidence was 0.67 cases per 10,000 patient-years in Martinique over the study period. To conclude, CP represents an increasing public health issue in Martinique, as is the case in other Caribbean islands. Patients present usual but possibly life-threatening features. Outcome is excellent despite frequently prolonged manifestations.

Rubigine® is an anti-rust stain remover containing fluorides which is believed to have been the cause of many deaths in Martinique. However, after the modification of its composition in 2006, serious poisoning from old formulas containing fluorides persisted. Our main objective was to determine the clinical characteristics and prognostic factors of these intoxications. Methods: Any patient admitted to the Martinique University Hospital for acute Rubigine® poisoning was included from 1 January 2000 to 31 December 2016. Usual demographic and clinical data were collected and comparisons between surviving and deceased patients made using a univariate analysis and logistic regression. Results: Fifty-five patients were included (mean age: 43 years; sex ratio M/F: 1.1), and the main clinical characteristics were: changes in electrocardiogram (ECG) (80%), digestive system disorders (75%), and neurological disorders (12%). The main features linked to death were the presence of hydrofluoric acid (p < 0.0001), age over 55 years (p = 0.01), hypocalcemia after the initial intravenous calcium supplementation (p = 0.0003), diarrhea (p < 0.0001), hypersialorrhea (p < 0.0001), myocardial excitability (p < 0.0001), and state of shock (p < 0.0001). Three patients required circulatory support by venous-arterial ECMO. Mortality was 10.9%. Conclusions: Rubigine® poisoning is responsible for significant morbidity and mortality. Fortunately, its incidence as well as mortality has sharply decreased in Martinique thanks to the measures taken by the French state. This retrospective work nevertheless shows that acute intoxication by the old formula of Rubigine® remains the main factor of poor prognosis.

AimsMetabolic syndrome induces cardiac dysfunction associated with mitochondria abnormalities. As low levels of carbon monoxide (CO) may improve myocardial and mitochondrial activities, we tested whether a CO-releasing molecule (CORM-3) reverses metabolic syndrome-induced cardiac alteration through changes in mitochondrial biogenesis, dynamics and autophagy.Methods and resultsMice were fed with normal diet (ND) or high-fat diet (HFD) for twelve weeks. Then, mice received two intraperitoneal injections of CORM-3 (10 mg x kg(-1)), with the second one given 16 hours after the first. Contractile function in isolated hearts and mitochondrial parameters were evaluated 24 hours after the last injection. Mitochondrial population was explored by electron microscopy. Changes in mitochondrial dynamics, biogenesis and autophagy were assessed by western-blot and RT-qPCR. Left ventricular developed pressure was reduced in HFD hearts. Mitochondria from HFD hearts presented reduced membrane potential and diminished ADP-coupled respiration. CORM-3 restored both cardiac and mitochondrial functions. Size and number of mitochondria increased in the HFD hearts but not in the CORM-3-treated HFD group. CORM-3 modulated HFD-activated mitochondrial fusion and biogenesis signalling. While autophagy was not activated in the HFD group, CORM-3 increased the autophagy marker LC3-II. Finally, ex vivo experiments demonstrated that autophagy inhibition by 3-methyladenine abolished the cardioprotective effects of CORM-3.ConclusionCORM-3 may modulate pathways controlling mitochondrial quality, thus leading to improvements of mitochondrial efficiency and HFD-induced cardiac dysfunction.

Anthracyclines remain the cornerstone of treatment in many malignancies but these agents have a cumulative dose relationship with cardiotoxicity. Development of cardiomyopathy and congestive heart failure induced by anthracyclines are typically dose-dependent, irreversible, and cumulative. Although past studies of cardiotoxicity have focused on anthracyclines, more recently interest has turned to anticancer drugs that target many proteins kinases, such as tyrosine kinases. An attractive model to explain the mechanism of this cardiotoxicity could be myocyte loss through cell death pathways. Inhibition of mitochondrial transition permeability is a valuable tool to prevent doxorubicin-induced cardiotoxicity. In response to anthracycline treatment, activation of several protein kinases, neuregulin/ErbB2 signaling, and transcriptional factors modify mitochondrial functions that determine cell death or survival through the modulation of mitochondrial membrane permeability. Cellular response to anthracyclines is also modulated by a myriad of transcriptional factors that influence cell fate. Several novel targeted chemotherapeutic agents have been associated with a small but worrying risk of left ventricular dysfunction. Agents such as trastuzumab and tyrosine kinase inhibitors can lead to cardiotoxicity that is fundamentally different from that caused by anthracyclines, whereas biological effects converge to the mitochondria as a critical target.