Impact of antivenom administration on the evolution of cutaneous lesions in loxoscelism: a prospective observational study

Background Spiders of the genus Loxosceles are distributed throughout tropical and temperate regions worldwide. Loxosceles spp. bites may evolve to necrosis, with or without intravascular hemolysis. There is no consensus regarding the best treatment to prevent necrosis. The objective of this study was to evaluate the factors associated with the development of necrosis and the impact that antivenom administration has on the evolution of cutaneous loxoscelism. Methodology/Principal findings This was a prospective observational study carried out at a referral center for envenoming. Over a 6-year period, we included 146 patients with a presumptive or definitive diagnosis of loxoscelism. Depending on the symptom severity, a polyvalent anti-arachnid antivenom was administered or not—in 74 cases (50.7%) and 72 cases (49.3%), respectively. Cutaneous and systemic manifestations were assessed at admission and weekly thereafter. Adverse reactions to the antivenom were also evaluated. Cutaneous loxoscelism was observed in 141 cases (96.6%), and the spider was identified in 29 (19.9%). The mean time from bite to antivenom administration was 41.6 ± 27.4 h. After discharge, 130 patients (90.9%) were treated with corticosteroids, antihistamines and analgesics being prescribed as needed. The probability of developing necrosis was significantly lower among the patients who were admitted earlier, as well as among those who received antivenom (p = 0.0245). Among the 74 patients receiving antivenom, early and delayed adverse reactions occurred in seven (9.5%) and four (5.4%), respectively. Local infection was observed only in three (2.3%) of the 128 patients for whom that information was available. Conclusions/Significance Necrosis after a Loxosceles sp. bite appears to more common when hospital admission is delayed or when antivenom is not administered. In addition, the administration of a polyvalent anti-arachnid antivenom appears to be safe, with a relatively low rate of adverse reactions.

Intensive care unit staff preparedness as an independent factor for death of patients during COVID-19 pandemic: An observational cohort study.

The pandemic of COVID-19 brought to the world an unprecedented challenge. This single center observational study aimed to evaluate the impact of staff preparedness by comparing the outcomes between two intensive care units (ICUs) from a hospital that had to expand ICU beds to deal with an incremented volume of critical patients. Patients consecutively admitted to these ICUs with suspected COVID-19, from March 1st until April 30th, 2020, were included. Both ICUs attended a similar population and had the same facilities, what differed was the staff: one previously well-established (ICU-1) and another recently assembled (ICU-2). 114 patients with severe respiratory syndrome were included. In-hospital mortality was 40%. Compared with patients in the well-established ICU-1, patients in the recently assembled ICU-2 were older (54 versus 61.5, p=0.045), received more antibiotics (93% versus 98%, p=0.001) and chloroquine/hydroxychloroquine 6% versus 30%, p=0.001), had a higher proportion of invasive mechanical ventilation (44% versus 52%, p=0.008) and had greater in-hospital mortality (30% versus 50%, p=0.017). The proportion of patients considered at high risk for death according to PSI was similar between the two ICU populations. Age ≥ 60 years (adjusted OR 2.33; 95% CI 1.02-5.31), need of invasive mechanical ventilation (adjusted OR 2.79; 95% CI 1.22-6.37), and ICU type (recently assembled) (adjusted OR 2.38; 95% CI 1.04-5.44) were independently associated with in-hospital mortality . This finding highlights the importance of developing support strategies to improve preparedness of staff recently assembled to deal with emergencies.

Splenic Infarction with Aortic Thrombosis in COVID-19.

Coronavirus disease 2019 (COVID-19) has been associated with an increased risk of venous and arterial thrombotic disease. Although pulmonary embolism has been the most common thrombotic complication, there have been recent reports of COVID-19-associated large-vessel ischemic stroke, acute upper- and lower-limb ischemia, as well as infarctions of the abdominal viscera, including renal, splenic, and small bowel infarctions. Here, we describe a case of splenic infarction (SI) associated with aortic thrombosis, which evolved despite the prophylactic use of low-molecular-weight heparin (LMWH), in a 60-year-old female patient with COVID-19. The patient was treated clinically with a therapeutic dose of LMWH, followed by warfarin, and eventually presented a favorable outcome. We also present a review of the literature regarding SI in patients with COVID-19.

Prone positioning to improve oxygenation and relieve respiratory symptoms in awake, spontaneously breathing non-intubated patients with COVID-19 pneumonia.

Emergency departments are facing an unprecedented challenge in dealing with patients who have coronavirus disease 2019 (COVID-19). The massive number of cases evolving to respiratory failure are leading to a rapid depletion of medical resources such as respiratory support equipment, which is more critical in low- and middle-income countries. In this context, any therapeutic and oxygenation support strategy that conserves medical resources should be welcomed. Prone positioning is a well-known ventilatory support strategy to improve oxygenation levels. Self-proning can be used in the management of selected patients with COVID-19 pneumonia. Here, we describe our experience with two COVID-19-positive patients who were admitted with respiratory failure. The patients were successfully managed with self-proning and noninvasive oxygenation without the need for intubation.

Prone positioning to improve oxygenation and relieve respiratory symptoms in awake, spontaneously breathing non-intubated patients with COVID-19 pneumonia

Emergency departments are facing an unprecedented challenge in dealing with patients who have coronavirus disease 2019 (COVID-19). The massive number of cases evolving to respiratory failure are leading to a rapid depletion of medical resources such as respiratory support equipment, which is more critical in low- and middleincome countries. In this context, any therapeutic and oxygenation support strategy that conserves medical resources should be welcomed. Prone positioning is a well-known ventilatory support strategy to improve oxygenation levels. Self-proning can be used in the management of selected patients with COVID-19 pneumonia. Here, we describe our experience with two COVID-19-positive patients who were admitted with respiratory failure. The patients were successfully managed with self-proning and noninvasive oxygenation without the need for intubation

Efficacy of sofosbuvir as treatment for yellow fever: protocol for a randomised controlled trial in Brazil (SOFFA study).

INTRODUCTION: An ongoing outbreak of yellow fever (YF) has been reported in Brazil with 1261 confirmed cases and 409 deaths since July 2017. To date, there is no specific treatment available for YF. Recently published papers describing in vitro and animal models suggest a potential effect of antiviral drugs (approved for the treatment of hepatitis virus) against flaviviruses, including YF. The primary aim of this study is to analyse the effect of sofosbuvir on viral kinetics and clinical outcomes among patients presenting with YF. This is a multicentre open-label randomised controlled trial with 1:1 individual allocation, stratified by severity and by recruiting centre. METHODS AND ANALYSIS: Adults with suspected or confirmed YF infection and symptoms lasting up to 15 days are screened. Eligible and consenting patients are randomised to receive oral sofosbuvir 400 mg daily for 10 days or to receive standard clinical care. Viral kinetics are measured daily and the reduction in YF plasma viral load from the sample at inclusion to 72 hours after randomisation will be compared between active and control groups. Clinical outcomes include severity meeting criteria for intensive care support, liver transplantation, in-hospital mortality and mortality within 60 days. ETHICS AND DISSEMINATION: Ethics approval was obtained at the participating sites and at the national research ethics committee (CAAE 82673018.6.1001.0068). The trial has been submitted for ethical approval at additional potential recruiting centres. Results of the study will be published in journals and presented at scientific meetings. TRIAL REGISTRATION: Brazilian Clinical Trials Registry (RBR-93dp9n).

Severe yellow fever and extreme hyperferritinemia managed with therapeutic plasma exchange

A 43-year-old man was admitted to the intensive care unit and diagnosed with yellow fever. He presented with refractory bleeding, extreme hyperferritinemia, and multiple organ dysfunction syndrome, requiring renal replacement therapy, mechanical ventilation, and treatment with vasoactive drugs. Because the bleeding did not respond to fresh-frozen plasma administration, the patient received therapeutic plasma exchange, which was accompanied by a marked improvement of the clinical and biochemical parameters, including a significant decline in serum ferritin levels

Yellow fever: factors associated with death in a hospital of reference in infectious diseases, São Paulo, Brazil, 2018

Faced with the reemergence of yellow fever (YF) in the metropolitan region of São Paulo, Brazil, we developed a retrospective study to describe the cases of YF attended at the Institute of Infectology Emilio Ribas from January to March 2018 and analyze the factors associated with death, from the information obtained in the hospital epidemiological investigation. A total of 72 cases of sylvatic YF were confirmed, with 21 deaths (29.2% lethality rate). Cases were concentrated in males (80.6%) and in the age group of 30 to 59 years (56.9%). Two logistic regression models were performed, with continuous variables adjusted for the time between onset of symptoms and hospitalization. The first model indicated age (odds ratiosadjusted [ORadj]: 1.038; CI 95%: 1.008-1.212), aspartate aminotransferase (AST) (ORadj: 1.038; CI 95%: 1.005-1.072), and creatinine (ORadj: 2.343; CI 95%: 1.205-4.553) were independent factors associated with mortality. The second model indicated age (ORadj: 1.136; CI 95%: 1.013-1.275), alanine aminotransferase (ALT) (ORadj: 1.118; CI 95%: 1.018-1.228), and creatinine (ORadj: 2.835; CI 95%: 1.352-5,941). The risk of death in the model with continuous variables was calculated from the increase of 1 year (age), 1 mg/dL (creatinine), and 100 U/L for AST and ALT. Another logistic regression analysis with dichotomous variables indicated AST > 1,841 IU/L (ORadj: 12.92; CI 95%: 1.50-111.37) and creatinine > 1.2 mg/dL (ORadj: 81.47; CI 95%: 11.33-585.71) as independent factors associated with death. These results may contribute to the appropriate clinical management of patients with YF in health-care services and improve the response to outbreaks and public health emergencies

Acute kidney injury induced by thrombotic microangiopathy in two cases of Bothrops envenomation

Context: Bothrops snakes are the most frequent agents of snakebites in South and Central America. Acute kidney injury (AKI) is one of its complications and has multifactorial origin. Thrombotic microangiopathy (TMA)-induced AKI in snakebites is uncommon and is not described in Bothrops envenomation. Case details: We report two cases of patients bitten by young Bothrops jararaca who developed AKI induced by TMA. Both patients evolved with mild envenomation and received the specific antivenom within 4 h after the snakebite. None of them had hypotension or shock, bleeding or secondary infection. Patient 1 (P1) was diabetic and using oral hypoglycemic drugs, and patient 2 (P2) was hypertensive without regular use of medication. On admission, both patients had levels of fibrinogen lower than 35 mg/dL, D-dimer higher than 10,000 ng/mL. They evolved with AKI, thrombocytopenia, normal coagulation assays, anemia, lactate dehydrogenase (LDH) elevation, low haptoglobin levels, negative direct antiglobulin test, and presence of schizocytes in peripheral blood. Only P1 required renal replacement therapy, and plasmapheresis was not required. Both patients were discharged and did not require outpatient dialysis, and subsequently had normal creatinine levels. Discussion: TMA may occur in Bothrops jararaca envenomation, even in mild cases that received early specific antivenom.

Allopurinol attenuates acute kidney injury following Bothrops jararaca envenomation

Snakebites have been recognized as a neglected public health problem in several tropical and subtropical countries. Bothrops snakebites frequently complicate with acute kidney injury (AKI) with relevant morbidity and mortality. To date, the only treatment available for Bothrops envenomation is the intravenous administration of antivenom despite its several limitations. Therefore, the study of novel therapies in Bothrops envenomation is compelling. The aim of this study was to evaluate the protective effect of Allopurinol (Allo) in an experimental model of Bothrops jararaca venom (BJ)-associated AKI. Five groups of Wistar rats were studied: Sham, Allo, BJ, BJ+Allo, BJ+ipAllo. BJ (0.25 mg/kg) was intravenously injected during 40'. Saline at same dose and infusion rate was administered to Sham and Allo groups. Allo and BJ+Allo groups received Allo (300 mg/L) in the drinking water 7 days prior to Saline or BJ infusion respectively. BJ+ipAllo rats received intraperitoneal Allo (25 mg/Kg) 40' after BJ infusion. BJ rats showed markedly reduced glomerular filtration rate (GFR, inulin clearance) associated with intense renal vasoconstriction, hemolysis, hemoglobinuria, reduced glutathione and increased systemic and renal markers of nitro-oxidative stress (Nitrotyrosine). Allo ameliorated GFR, renal blood flow (RBF), renal vascular resistance and arterial lactate levels. In addition, Allo was associated with increased serum glutathione as well as reduced levels of plasma and renal Nitrotyrosine. Our data show that Allo attenuated BJ-associated AKI, reduced oxidative stress, improved renal hemodynamics and organ perfusion. It might represent a novel adjuvant approach for Bothrops envenomation, a new use for an old and widely available drug.

The role of dexamethasone in scorpion venom-induced deregulation of sodium and water transport in rat lungs.

BACKGROUND: Severe scorpion envenomation can evolve to lung injury and, in some cases, death. The lung injury could be attributed to acute left ventricular failure and increased pulmonary vascular permeability secondary to the release of inflammatory mediators. In clinical practice, corticosteroids have been administered to reduce the early side effects of the anti-venom. We propose to study the effects of Tityus serrulatus venom and dexamethasone on pulmonary expression of sodium and water transporters, as well as on the inflammatory response. METHODS: Wistar rats were injected intraperitoneally with saline (control group), dexamethasone, and saline (2.0 mg/kg body weight-60 min before saline injection; dexamethasone + saline group), venom (T. serrulatus venom-3.8 mg/kg body weight), or dexamethasone and venom (2.0 mg/kg body weight-60 min before venom injection; dexamethasone + venom group). At 60 min after venom/saline injection, experiments were performed in ventilated and non-ventilated animals. We analyzed sodium transporters, water transporters, and Toll-like receptor 4 (TLR4) by Western blotting, macrophage infiltration by immunohistochemistry, and serum interleukin (IL) by cytokine assay. RESULTS: In the lung tissue of non-ventilated envenomed animals, protein expression of the epithelial sodium channel alpha subunit (α-ENaC) and aquaporin 5 (AQP5) were markedly downregulated whereas that of the Na-K-2Cl cotransporter (NKCC1) and TLR4 was elevated although expression of the Na,K-ATPase alpha 1 subunit was unaffected. Dexamethasone protected protein expression of α-ENaC, NKCC1, and TLR4 but not that of AQP5. We found that IL-6, IL-10, and tumor necrosis factor alpha were elevated in the venom and dexamethasone + venom groups although CD68 expression in lung tissue was elevated only in the venom group. Among the ventilated animals, both envenomed groups presented hypotension at 50 min after injection, and the arterial oxygen tension/fraction of inspired oxygen ratio was lower at 60 min than at baseline. CONCLUSIONS: Our results suggest that T. serrulatus venom and dexamethasone both regulate sodium transport in the lung and that T serrulatus venom regulates sodium transport via the TLR4 pathway.

Estudo da ação do veneno de Tityus serrulatus sobre a expressão de transportadores de sódio e água em epitélio alveolar de rato / Effect of Tityus serrulatus venom on sodium and water trasporters in rat alveolar epithelium

Acidentes escorpiônicos podem evoluir com edema pulmonar de origem cardiogênica e não cardiogênica. O clearance de edema pulmonar está relacionado principalmente ao transporte ativo de sódio do espaço alveolar para o interstício. O objetivo deste trabalho foi avaliar os efeitos do veneno de Tityus serrulatus e da dexametasona sobre a expressão dos transportadores de sódio e água e do TLR4 em pulmão de ratos. Foram utilizados ratos Wistar, divididos em três grupos: controle (salina); grupo Vn, que recebeu o veneno de T. serrulatus (3.8 mg/kg) por via intraperitoneal (ip), e o grupo Dx+Vn, que recebeu dexametasona (2.0 mg/kg) por via ip, uma hora antes da injeção do veneno. Os experimentos foram realizados uma hora após a injeção do veneno. Foram realizadas análise bioquímica e dosagens de citocinas no plasma. Nos pulmões foram estudados a expressão de -ENaC, Na+-K+- ATPase, NKCC1, AQP-5 e TRL4 através de western blotting, e a expressão do NF-kB e infiltração de células CD68+ (monócitos/macrófagos) e neutrófilos, através de imunoistoquímica. O veneno de T. serrulatus diminuiu a expressão pulmonar de -ENaC e AQP-5, enquanto aumentou a expressão do NKCC1. A dexametasona preveniu os efeitos do veneno sobre a expressão da -ENaC e NKCC1, mas não da AQP5. Não foi observada alteração da expressão da 1- Na+-K+-ATPase . A expressão do TLR4 foi maior nos animais envenenados que nos grupos Cont e Dx+Vn. O níveis plasmáticos de IL-6, IL-10 e TNF- estavam aumentados nos grupo Vn e Dx+Vn em relação ao controle. O infiltrado de células CD68+ foi maior no grupo Vn. A expressão de NF-kB e o infiltrado ne neutrófilos no tecido pulmonar foi semelhantes nos três grupos avaliados. Os resultados encontrados sugerem que o veneno de T. serrulatus tem efeito sobre as proteínas transportadoras de sódio em células do epitélio alveolar e também sobre a expressão do TLR4 em pulmão; a dexametasona pode regular essas ações...

Scorpion envenomation can cause cardiogenic and noncardiogenic pulmonary edema. Pulmonary edema clearance is largely related to active Na+ transport out of the alveoli, rather than to reversal of Starling forces. Our objective was determine the effects of Tityus serrulatus venom and dexamethasone on the pulmonary expression of sodium and water transporters, and Toll-like receptor 4. Wistar rats were divided into groups and injected intraperitoneally: control (saline only); venom (T. serrulatus venom3.8 mg/kg body weight); and dexamethasone+venom (dexamethasone2.0 mg/kg body weight60 min before venom inoculation). At 60 min after venom inoculation, interleukin-6 and -10, together with tumor necrosis factor alpha, were analyzed in plasma. In lungs, we determined expression of the epithelial sodium channel alpha subunit; Na,K-ATPase alpha 1 subunit; Na-K-2Cl cotransporter, NKCC1; aquaporin 5; Toll-like receptor 4 (by Western blotting); and nuclear factor-kappa B. We determined CD68 and neutrophil counts by immunohistochemistry. In venom group lungs, the epithelial sodium channel alpha subunit and aquaporin 5 were markedly downregulated, whereas NKCC1 was elevated, although the Na,K-ATPase alpha 1 subunit was unaffected. Dexamethasone protected the epithelial sodium channel alpha subunit, NKCC1, and Toll-like receptor 4 but not aquaporin 5. Serum interleukin 6, interleukin 10, and tumor necrosis factor alpha were elevated in both groups, as was CD68 expression. Neutrophil counts and nuclear factor-kappa B expression were comparable across groups. Our data show that T. serrulatus venom alters sodium transport in alveolar epithelial cells and increases Toll-like receptor 4 expression. Dexamethasone appears to partially protect against those effects...