Innate immune response in acute critical illness: a narrative review.

BACKGROUND: Activation of innate immunity is a first line of host defense during acute critical illness (ACI) that aims to contain injury and avoid tissue damages. Aberrant activation of innate immunity may also participate in the occurrence of organ failures during critical illness. This review aims to provide a narrative overview of recent advances in the field of innate immunity in critical illness, and to consider future potential therapeutic strategies. MAIN TEXT: Understanding the underlying biological concepts supporting therapeutic strategies modulating immune response is essential in decision-making. We will develop the multiple facets of innate immune response, especially its cellular aspects, and its interaction with other defense mechanisms. We will first describe the pathophysiological mechanisms of initiation of innate immune response and its implication during ACI. We will then develop the amplification of innate immunity mediated by multiple effectors. Our review will mainly focus on myeloid and lymphoid cellular effectors, the major actors involved in innate immune-mediated organ failure. We will third discuss the interaction and integration of innate immune response in a global view of host defense, thus considering interaction with non-immune cells through immunothrombosis, immunometabolism and long-term reprogramming via trained immunity. The last part of this review will focus on the specificities of the immune response in children and the older population. CONCLUSIONS: Recent understanding of the innate immune response integrates immunity in a highly dynamic global vision of host response. A better knowledge of the implicated mechanisms and their tissue-compartmentalization allows to characterize the individual immune profile, and one day eventually, to develop individualized bench-to-bedside immunomodulation approaches as an adjuvant resuscitation strategy.

Sex-related differences in toxic manifestations induced by Bothrops atrox venom in mice.

Lancehead snakes of the genus Bothrops are responsible for 90% of the snakebites in Latin America. The objective of this study was to assess the LD50, physical, and hematological manifestations induced by B. atrox venom in male and female mice inoculated by different routes. B. atrox venom was inoculated in male and female mice by intramuscular (IM), subcutaneous (SC), intravenous (IV), and intraperitoneal (IP) routes. B. atrox venom LD50 was lower in male than female groups, regardless of the injection route. However, it was the lowest when the venom was inoculated by the IP route. Moreover, comparisons between male and female responses according to the injected venom dose showed higher edema-forming, local hemorrhagic, dermonecrotic, and myotoxic activities in male than in female mice. While the minimal hemorrhagic, and necrotic doses were not statistically different between the two groups, the difference between males and females was more pronounced at high venom doses. Hematological parameter changes were also more significant in male than in female mice. The venom decreased the levels of total leukocytes after 24 h of injection in male and female mice, with a more profound decrease in the male group. The micronucleus test, a tool for genotoxicity assessment, documented the mutagenic effects of B. atrox on leucocytes. We demonstrate the higher susceptibility of male mice to B. atrox venom than females. Sex differences must be considered when conducting experimental studies on snake venoms.

Contribution of international cooperation in the management of the first documented case of Lonomia caterpillar envenoming (Lonomism) in Guyana.

Severe Lonomia caterpillar envenoming is an increasing hazard in South America. It can trigger severe coagulation disorders that can progress to systemic complications and death. We report the first documented case of severe Lonomia caterpillar envenoming in Guyana. It was managed using antivenom provided by the Brazilian Ministry of Health as part of humanitarian support. This case describes a successful international collaboration driving a favorable outcome for the envenomed patient.

Inequalities in access to antivenom: An ethical issue in the management of snakebite envenoming.

Snakebite envenoming is a high-priority neglected tropical disease and antivenom is the cornerstone of treatment. Antivenom is listed among essential medicines and its access must be considered as a human right. Despite resolutions from various international organizations including the WHO, antivenom remains unavailable, unaffordable, and sometimes not targeted against the specific snake involved. Also, despite an expanding global antivenom market, some manufacturers have stopped production due to a lack of profits. However, justice and equitable access to care according to medical needs are among the four pillars of medical ethics. Overall, snakebite envenoming is a typical example of social and ethnic inequity in medicine. It is imperative that this issue be addressed from an ethical standpoint and that government laboratories take the lead in antivenom production.

An Observational Study of Sexual Assaults in French Guiana During 2019-2020.

Introduction: Sexual violence is a major public health issue, including in French Guiana. The feeling of insecurity is significant in this part of France. Sexual violence is an important reason for consultation in forensic and emergency medicine. The challenge is to provide care within the first 72 hours, particularly in medicolegal terms and for infectious disease management. The objectives of our study were, firstly, to establish the epidemiology of sexual assaults at Cayenne General Hospital (CGH), and secondly, to evaluate the management of these victims. Materials and Methods: From January 1st, 2019 to December 31st, 2020, we conducted a single-center retrospective descriptive study including patients who were consulted for sexual assaults in the Forensic medicine and the Emergency departments of CGH. Results: Over this period, 400 sexual assault victims were consulted. Most of them, were women (87%) with a median age of 13 years-old [8; 17.5]. The aggressor was mostly male (99%) frequently known by the victim (87%) and from her family (39%). Suspected assaults represented 19% of consultations. The most frequent assault on women was penile-vaginal penetration (82%) and penile-anal penetration (77%) on men. The delay of consultation was superior to 72 hours in 60% of the cases. A psychological follow-up was recommended for 62% of these victims. Conclusion: This work allowed to identify a young and female population at risk, most often assaulted by a male known to her. Most of the patients consulted more than 72 hours after the assault. Our study highlights the need for prevention actions in French Guiana focusing on this population at risk.

Histoplasmosis in Non-HIV Infected Patients: Another Neglected Infection in French Guiana.

(1) Background: Only a few studies on histoplasmosis in immunocompetent patients have been reported in French Guiana. Therefore, we conducted a detailed clinical description of hospitalized patients suffering with histoplasmosis among non-HIV patients. (2) Methods: This is a single-center, retrospective study conducted at Cayenne Hospital Center between 2008 and 2022. (3) Results: Our cohort was composed of 31 (91%) adults (>18 years of age) and 3 (9%) children, with a sex ratio, M:F, of 1:2. The median age was higher among the women than among the men (70 versus 54 years). The collection of respiratory samples constituted the majority of the performed examinations (38%). Fever (>37 °C) was found in 56% of patients. Surprisingly, the histoplasmosis was disseminated in 82% of patients with an overall case fatality rate of 14.7%. However, immunosuppressive conditions were found in 52% (16/31) of the adult patients, including lymphoid hemopathies, diabetes and immunosuppressive drugs. Conclusions: This disease, though rare and usually considered a mostly benign disease in non-HIV patients, presented a relatively high mortality rate in our cohort. Thus, histoplasmosis should be suspected, screened and investigated as a first line of defense in highly endemic areas, even in immunocompetent and non-HIV patients, especially those with fever or chronic respiratory symptoms.

Inadequate intensive care physician supply in France: a point-prevalence prospective study.

BACKGROUND: The COVID-19 pandemic has highlighted the importance of intensive care units (ICUs) and their organization in healthcare systems. However, ICU capacity and availability are ongoing concerns beyond the pandemic, particularly due to an aging population and increasing complexity of care. This study aimed to assess the current and future shortage of ICU physicians in France, ten years after a previous evaluation. A national e-survey was conducted among French ICUs in January 2022 to collect data on ICU characteristics, medical staffing, individual physician characteristics, and education and training capacities. RESULTS: Among 290 ICUs contacted, 242 responded (response rate: 83%), representing 4943 ICU beds. The survey revealed an overall of 300 full time equivalent (FTE) ICU physician vacancies in the country. Nearly two-thirds of the participating ICUs reported at least one physician vacancy and 35% relied on traveling physicians to cover shifts. The ICUs most affected by physician vacancies were the ICUs of non-university affiliated public hospitals. The retirements expected in the next five years represented around 10% of the workforce. The median number of physicians per ICU was 7.0, corresponding to a ratio of 0.36 physician (FTE) per ICU bed. In addition, 27% of ICUs were at risk of critical dysfunction or closure due to vacancies and impending retirements. CONCLUSION: The findings highlight the urgent need to address the shortage of ICU physicians in France. Compared to a similar study conducted in 2012, the inadequacy between ICU physician supply and demand has increased, resulting in a higher number of vacancies. Our study suggests that, among others, increasing the number of ICM residents trained each year could be a crucial step in addressing this issue. Failure to take appropriate measures may lead to further closures of ICUs and increased risks to patients in this healthcare system.

Protective effects of polysaccharide extracted from green alga Chaetomorpha linum against zinc and copper-induced testicular toxicity in male mice.

This study aimed to investigate the effects of copper (CuSO4) and zinc (ZnSO4) overload on male reproductive toxicity and the potential of a polysaccharide extracted from green alga Chaetomorpha linum (PS) in mitigating their toxicities. Adult male mice strain of 25 ± 2 g of weight was subdivided into eight groups. Group 1 served as control; group 2 received PS (200 mg/kg), and groups 3 and 4 received intraperitoneally zinc (60 mg/kg b.w) and copper (33 mg/kg b.w), respectively. Group 5 received both zinc (60 mg/kg b.w) and copper (33 mg/kg b.w), group 6 received zinc (60 mg/kg b.w) associated with PS (200 mg/kg), group 7 received copper (33 mg/kg b.w) associated with PS (200 mg/kg), and group 8 received zinc (60 mg/kg b.w) and copper (33 mg/kg b.w) associated with PS (200 mg/kg). Results suggested that ZnSO4 and CuSO4 significantly decreased the functional sperm parameters. Furthermore, extended exposure to these elements increased oxidative stress biomarkers, including malondialdehyde (MDA) as a measure of lipid peroxidation and advanced oxidation protein products (AOPP) indicating protein oxidative damage. This process also reduces the activity of antioxidant enzymes such as glutathione (GSH) and glutathione peroxidase (GPx), which neutralize and catalyze free radicals. Histopathological changes in mice testis were also studied. However, the co-treatments with PS significantly reduced these effects and promoted the reproductive parameters in male mice. In conclusion, PS exhibited protective effects against zinc and copper-induced reproductive toxicity, making it a potential adjuvant treatment for testicular toxicity.

Trends in the Prevalence of Antimicrobial Resistance in Escherichia coli Isolated from Outpatient Urine Cultures in French Amazonia.

Antimicrobial resistance (AMR) in the community is increasing worldwide. We aimed to assess AMR trends in Escherichia coli from the community urine isolates in French Amazonia. We conducted a retrospective study from January 2016 to December 2022 in the Cayenne General Hospital microbiology laboratory (French Guiana). It included all urine samples positive for E. coli collected from adult outpatients. During the study period, 3,443 urinalyses positive for E. coli were studied. In 46% of cases, patients were women. In 64.4% of cases, E. coli were ß-lactamase producers. The most frequently diagnosed resistance mechanisms were penicillinase production and sparing third-generation cephalosporins. Isolated E. coli were extended-spectrum ß-lactamase (ESBL) producers in 6.1% of cases. Overall, E. coli was susceptible to amoxicillin in 35.9% [95% CI: 34.3-37.5], to amoxicillin/clavulanic acid in 62.2% [95% CI: 60.6-63.9], to cefotaxime in 94% [95% CI: 93.1-94.7], to gentamicin in 92.1% [95% CI: 89.1-92.6], to ofloxacin in 76.8% [95% CI: 75.3-78.2], to trimethoprim/sulfamethoxazole (SXT) in 58.8% [95% CI: 57.1-60.5], to fosfomycin in 99.1% [95% CI: 98.6-99.4], and to nitrofurantoin in 99% of cases [95% CI: 98.6-99.3]. We have observed a gradual decline in the susceptibility profile of E. coli for amoxicillin/clavulanic acid (P <0.001), piperacillin/tazobactam (P = 0.003), and temocillin (P = 0.006). However, susceptibility to ciprofloxacin was increasing (P = 0.001). In contrast, the susceptibility trends for amoxicillin, third-generation cephalosporins, gentamicin, SXT, nitrofurantoin, and fosfomycin remained stable over the 28 quarters of the study. In conclusion, isolated E. coli from outpatient urinalyses showed increased resistance profiles involving penicillinase and ESBL production. Close monitoring and strategies to decrease antibiotic consumption in the community are needed.

Anti-Vasculogenic, Antioxidant, and Anti-Inflammatory Activities of Sulfated Polysaccharide Derived from Codium tomentosum: Pharmacokinetic Assay.

The purpose of this paper was to investigate the anti-inflammatory and anti-angiogenic activities of sulfated polysaccharide from C. tomentosum (PCT) using carrageenan (CARR)-induced paw edema in a rat model and anti-vasculogenic activity on a chorioallantoic membrane assay (CAM) model. Based on in vitro tests of anti-radical, total antioxidant, and reducing power activities, PCT presents a real interest via its antioxidant activity and ability to scavenge radical species. The in vivo pharmacological tests suggest that PCT possesses anti-inflammatory action by reducing paw edema and leukocyte migration, maintaining the redox equilibrium, and stabilizing the cellular level of several pro-/antioxidant system markers. It could significantly decrease the malondialdehyde levels and increase superoxide dismutase, glutathione peroxidase, and glutathione activities in local paw edema and erythrocytes during the acute inflammatory reaction of CARR. PCT pretreatment was effective against DNA alterations in the blood lymphocytes of inflamed rats and reduced the hematological alteration by restoring blood parameters to normal levels. The anti-angiogenic activity results revealed that CAM neovascularization, defined as the formation of new vessel numbers and branching patterns, was decreased by PCT in a dose-dependent manner, which supported the in silico bioavailability and pharmacokinetic findings. These results indicated the therapeutic effects of polysaccharides from C. tomentosum and their possible use as anti-proliferative molecules based on their antioxidant, anti-inflammatory, and anti-angiogenic activities.

First French and Indonesian university medical cooperation for promoting emergency medicine.

Indonesia and French Guiana share many geographic and medical concerns regarding access to care. The organisational needs in emergency management, particularly in the prehospital phase, are similar. Whereas emergency medicine (EM) is an academic and entire speciality in France, it is still under construction in Indonesia. In the framework of the French and Indonesian academic cooperation, the Medical school in Jakarta University and the French Guiana University in Cayenne signed a Memorandum of Understanding encompassing education programmes, joint research work and students' and health professionals' exchanges in EM. This partnership represented the first medical cooperation programme between the two countries. The first student class was launched in August 2022 and involved 50 Indonesian doctors who graduated in August 2023. The implementation and success of this Franco-Indonesian cooperation were supported by political and academic partners from the two sides. Given the first student class's success, we aim to continue this programme, in line with Indonesia and World Health Organization's plan to establish a multi-country training hub for health emergency operational readiness and Emergency Medical Teams.

Bothrops lanceolatus Envenoming in Martinique: A Historical Perspective of the Clinical Effectiveness of Bothrofav Antivenom Treatment.

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.

Clinical and Epidemiological Characteristics of Severe Acute Adult Poisonings in French Amazonia: Urgent Need for a Toxicovigilance Monitoring Framework.

BACKGROUND: Acute poisonings (AP) are a significant public health problem, accounting for a high number of emergency department visits and thousands of deaths worldwide. This study aimed to assess the epidemiology of AP in an adult population admitted to Cayenne Hospital (French Guiana) and to investigate the clinical and sociodemographic characteristics. METHODS: We conducted a monocentric retrospective study from January 2010 to December 2022, including patients over eighteen years of age who had been admitted to the emergency department of Cayenne Hospital for acute poisoning. RESULTS: We included 425 patients. The median age was 34 years (IQR: 25-47). The sex ratio (M/F) was 0.52. A psychiatric disorder was found in 41.9% of patients. The Poisoning Severity Score (PSS) on admission was 1 or 2 for 84% of patients, and the mortality rate was 3.9%. The main involved toxicants were psychotropic drugs (43.1%), benzodiazepines (34.8%), and paracetamol (25.6%). The most lethal toxic was paraquat (5.2%). Intoxication was due to intentional self-poisoning in 84.2% of cases. Independent factors associated with severe poisoning (PSS 3 or 4) were chloroquine, neuroleptics, or paraquat poisoning; metabolic acidosis; and hyperglycemia (>5.5 mmol/L). The mortality rate was 3.9%, and the most involved toxic in death was paraquat. CONCLUSION: This study shows the frequent and deadly use of paraquat in APs in French Guiana. Urgent attention should be given to establishing a toxicovigilance monitoring framework and an antipoison center in the region.

Epidemiologic analysis and mortality outcome of firearm injuries in French Guiana (2016-2019).

BACKGROUND: French Guiana (FG) is a French territory located in South America with the highest rate of armed assaults. FG presents a poorly developed road system and a young and precarious population that makes the geographical and socio-demographic characteristics specific. No data concerning the firearm injury management are available in this country. Studying thesis trauma could permit to improve the management of victims. The objective of this study is to investigate the epidemiology of firearm injuries in FG, to define characteristics of the victims, and to assess factors associated with death. These identified factors could enable target primary prevention and intensification of medical management. METHODS: From January 2016 to December 2019, we conducted a retrospective study at the Cayenne General Hospital (CGH), including all patients admitted for firearm injuries in the emergency department, the medical emergency and resuscitation service, and the forensic service. A bivariate analysis was performed to assess relevant clinical data that were entered into a logistic regression model to assess factors associated with death. RESULTS: A total of 871 files were analyzed concerning 340 patients included after cross-checking. Victims were mainly males (90%) and young (30 ± 11 years old). The injury occurred mainly at night (60%), in a context of assaults (83%) and with long-barreled guns (82%). Among the 290 patients managed at the CGH, 60% were hospitalized including 12% that were in the intensive care unit, 41% that required surgical treatment, and 7% that died in hospital. The overall average length of stay was 10 ± 18 days. Overall mortality (n = 71, 21%) is statistically associated with male gender (p = 0.007) and suicide context (p < 0.001). In multivariate analysis, the sites of wounds (head and neck, thorax; p < 0.001) as well as induced organ injuries (neurological, respiratory, and vascular; p < 0.005) were independent factors associated to mortality. CONCLUSIONS: This work underlines the high incidence of ballistic trauma in FG. This mainly involves a young and male population linked to the use of long arms and assaults. Despite the geographical difficulties of the territory and the technical platform deficits (no neurosurgery, no cardiothoracic surgery, no interventional radiology), the mortality is comparable to other studies, but remains more than twice as high as in mainland France. Finally, despite a change in legislation restricting access to firearms, our results show that gunshot firearm injuries remain a major public health concern requiring greater political actions.

Anti-Inflammatory and Immunomodulatory Properties of a Crude Polysaccharide Derived from Green Seaweed Halimeda tuna: Computational and Experimental Evidences.

In this study, we investigated for the first time the anti-inflammatory and immunomodulatory properties of crude polysaccharide (PSHT) extracted from green marine algae Halimeda tuna. PSHT exhibited anti-oxidant activity in vitro through scavenging 1, 1-diphenyl-2-picryl hydroxyl free radical, reducing Fe3+/ferricyanide complex, and inhibiting nitric oxide. PSHT maintained the erythrocyte membrane integrity and prevented hemolysis. Our results also showed that PSHT exerted a significant anti-edematic effect in vivo by decreasing advanced oxidation protein products and malondialdehyde levels and increasing the superoxide dismutase and glutathione peroxidase activities in rat's paw model and erythrocytes. Interestingly, PSHT increased the viability of murine RAW264.7 macrophages and exerted an anti-inflammatory effect on lipopolysaccharide-stimulated cells by decreasing pro-inflammatory molecule levels, including nitric oxide, granulocyte-macrophage colony-stimulating factor (GM-CSF) and tumor necrosis factor-alpha (TNF-α). Our findings indicate that PSHT could be used as a potential immunomodulatory, anti-inflammatory, anti-hemolytic, and anti-oxidant agent. These results could be explained by the computational findings showing that polysaccharide building blocks bound both cyclooxygenase-2 (COX-2) and TNF-α with acceptable affinities.

Mortality Trend of Severe COVID-19 in Under-Vaccinated Population Admitted to ICU in French Amazonia.

(1) Background: Until December 2021, French Guiana (FG), located in South America, faced four consecutive COVID-19 epidemic waves. This study sought to analyze the mortality trend of severe COVID-19 patients admitted to the referral ICU of FG. (2) Methods: We conducted a prospective, observational, and non-interventional study in ICU at Cayenne Hospital. We included 383 patients older than 18 admitted with SARS-CoV-2-related pneumonia hospitalized from May 2020 to December 2021. The study covers three periods. Period 1 (Waves 1 and 2, original variant), period 2 (Wave 3, Gamma variant), and period 3 (Wave 4, Delta variant). (3) Results: The median age was 63 years (52-70). Frailty was diagnosed in 36 patients over 70 (32.4%). Only 4.8% of patients were vaccinated. The median ICU LOS was 10 days (6-19). Hospital mortality was 37.3%. It was 30.9% in period 1, 36.6% in period 2 (p = 0.329 vs. period 1), and 47.1% in period 3 (0.015 vs. period 1). In multivariate analysis, independent factors associated with hospital mortality included age greater than 40 years (]40-60 years] OR = 5.2, 95%CI: 1.4-19.5; (]60-70 years] OR = 8.5, 95%CI: 2.2-32; (]70+ years] OR = 17.9, 95%CI: 4.5-70.9), frailty (OR = 5.6, 95%CI: 2.2-17.2), immunosuppression (OR = 2.6, 95%CI: 1.05-6.7), and MV use (OR = 11, 95%CI: 6.1-19.9). This model had an overall sensitivity of 72%, a specificity of 80.4%, a positive predictive value of 68.7%, and a negative predictive value of 82.8%. (4) Conclusions: The mortality of severe COVID-19 patients in French Amazonia was higher during the Delta variant wave. This over-death could be explained by the virulence of the responsible SARS-CoV-2 variant and the under-vaccination coverage of the studied population.

Addressing snakebite envenoming as a One Health issue in the Caribbean

The prevalence of snakebite envenoming and its understated impact on health and socioeconomic well-being in the Caribbean demand urgent attention. As a One Health challenge, this issue intersects human, animal, and environmental health, necessitating a multifaceted approach for comprehensive management. Despite the Caribbean’s rich biodiversity and cultural mosaic, there is a scarcity of data on the epidemiology and impact of snakebites in the region. This gap in knowledge, coupled with the absence of systematic records or survey-based studies, hampers the development of effective interventions. In countries such as Belize, Saint Lucia, and Trinidad and Tobago, among others, venomous snakes pose a significant threat, particularly to those in rural agricultural settings. Snakebite envenoming not only inflicts a direct health burden, evidenced by high rates of mortality and morbidity among humans, but also precipitates profound financial repercussions. The cost of clinical management for those affected and the loss of productivity due to long-term sequelae are considerable. Moreover, the impact on domestic animals, primarily livestock, translates into tangible economic losses for rural households, who rely on these animals for sustenance and income.