[Loxoscelism with acute compartment síndrome: A case report with successful conclusion]. / Loxoscelismo con síndrome compartimental agudo: reporte de un caso con desenlace exitoso.

BACKGROUND: Loxoscelism is a toxic clinical condition caused by the bite of spiders of the genus Loxosceles, with wide distribution throughout the world.1 Phospholipase D is responsible for dermonecrosis, inflammation, platelet aggregation, hemolysis, alteration of vascular permeability, cytotoxicity, nephrotoxicity, acute renal failure, among other symptoms involved with this protein. CASE REPORT: 27-year-old male patient, who began with a sudden episode of intense pain in the right hand, in the metacarpus and metacarpophalangeal joints. On clinical examination, the upper extremity was noted to have increased volume, extensive edema, hyperemia, and increased local temperature; The lesion progressed to extensive necrosis. Fasciotomies were performed, from distal to proximal, and release of the second and third finger compartment through longitudinal radial and ulnar incisions. A skin autograft was placed, obtained from the anterior surface of the right thigh. Opioid analgesics, non-steroidal anti-inflammatory drugs, corticosteroids, and antibiotics were administered. The skin biopsy reported: inflammatory infiltrate with neutrophils, ulceration, and bacterial colonies. After 27 days he had a favorable evolution, so he was discharged to his home, with follow-up by staff from the Outpatient Service. CONCLUSION: Cutaneous loxoscelism, as a cause of acute compartment syndrome of the hand, is rare, but should be considered in an area endemic for Loxosceles spp. Surgical decompression of the affected compartments represents a decisive factor in the treatment of patients.

ANTECEDENTES: El loxoscelismo es un cuadro clínico tóxico provocado por la mordedura de arañas del género Loxosceles, con amplia distribución en todo el mundo.1 La fosfolipasa D es la responsable de la dermonecrosis, inflamación, agregación plaquetaria, hemólisis, alteración de la permeabilidad vascular, citotoxicidad, nefrotoxicidad, insuficiencia renal aguda, entre otros síntomas implicados con esta proteína. REPORTE DE CASO: Paciente masculino de 27 años, que inició con un cuadro repentino de dolor intenso en la mano derecha, en el metacarpo y las articulaciones metacarpofalángicas. Al examen clínico, la extremidad superior se percibió con aumento de volumen, edema extenso, hiperemia y aumento de la temperatura local; la lesión progresó a necrosis extensa. Se realizaron fasciotomías, de distal a proximal, y liberación del compartimento del segundo y tercer dedo a través de incisiones longitudinales radiales y cubitales. Se colocó un autoinjerto de piel, obtenido de la superficie anterior del muslo derecho. Se administraron analgésicos opioides, antiinflamatorios no esteroides, corticosteroides y antibióticos. La biopsia de piel reporto: infiltrado inflamatorio con neutrófilos, ulceración y colonias bacterianas. Luego de 27 días tuvo evolución favorable, por lo que se dio alta a su domicilio, con seguimiento por personal del servicio de Consulta externa. CONCLUSIÓN: El loxoscelismo cutáneo, como causa de síndrome compartimental agudo de la mano, es poco común, pero debe considerarse en un área endémica para Loxosceles spp. La descompresión quirúrgica de los compartimentos afectados representa un factor decisivo en el tratamiento de los pacientes.

The type 2 inflammatory response favors recognition of tumor antigens by IgE in breast cancer.

BACKGROUND: Several studies describe an inverse statistical relationship between the presence of an allergy and development of cancer. However, the immunological mechanism involved in the relationship between these two degenerative diseases has not been explored. AIMS: The main objective of this study was to explore the possibility that the lymphocyte T helper (Th) 2 response, a characteristic of allergy, induces recognition of tumor antigens. METHODS AND RESULTS: Patients with a clinical diagnosis of breast ductal carcinoma were included. Histopathological markers related to proliferation of tumor cells were determined (Her-2-neu, Ki-67, estrogen receptor, and progesterone receptor). IHC was performed using IgE antibodies purified from an allergy patient and from each biopsy donor patient. Serum concentrations of cytokines representative of Th1 and Th2 inflammatory responses were determined. A total of 14 patients with a confirmed diagnosis of breast ductal carcinoma were included. IHC performed on biopsies showed a weak response when using purified IgE antibodies from an allergy patient; however, IHC using the IgE of each patient as the primary antibody showed an intense and highly specific signal. Serum concentrations of cytokines of the Th2 response, that is, IL-4 (130.5 pg/mL (116-135 pg/mL)), IL-5 (202 pg/mL (191-213 pg/mL)), and IL-13 (105.5 pg/mL (98-117 pg/mL)), were significantly higher than those of the Th1 response, that is, IL-6 (86 pg/mL (79-90 pg/mL)) and INF-γ (93 pg/mL (79-99 pg/mL)). CONCLUSION: Purified IgE antibodies specifically recognize tumor cells in breast ductal carcinoma.

Clinical risk factors in patients with interstitial lung disease associated with anti-MDA5 autoantibodies.

INTRODUCTION: The anti-MDA5-associated autoimmune disease represents a poorly understood entity. The study's objectives were to describe a cohort of interstitial lung disease (ILD) patients who were positive for anti-MDA5 autoantibody and identify clinical risk factors associated with survival. METHODS: This single-center cohort study included ILD patients positive for anti-MDA5 autoantibody. Baseline clinical features were registered, and survival analysis was performed to identify risk factors associated with worse survival. RESULTS: Fifty-three ILD-MDA5 positive patients were included; twelve died during follow-up due to rapidly progressive interstitial lung disease (RP-ILD). Dermatological signs of anti-MDA5 (Gottron papules, Gottron sign, palmar papules, V-neck sign, facial dermatomyositis rashes, and skin ulcers) were strongly associated with death secondary to RP-ILD (HR: 3.7, 95% CI: 1.02-13.35). Patients with dermatological signs were younger, had higher anti-MDA5 autoantibodies titers, more frequent inflammatory patterns in HRCT evaluation, and less fibrosis extent in HRCT. CONCLUSION: Dermatological manifestation in ILD patients to anti-MDA5 autoantibodies are associated with RP-ILD and short-term fatal outcomes. Dermatological signs may identify a subgroup of ILD-positive to anti-MDA5 patients with a high risk of RP-ILD.

TNFRSF1B and TNF Variants Are Associated With Differences in Levels of Soluble Tumor Necrosis Factor Receptors in Patients With Severe COVID-19.

BACKGROUND: The impact of genetic variants in the expression of tumor necrosis factor-α (TNF-α) and its receptors in coronavirus disease 2019 (COVID-19) severity has not been previously explored. We evaluated the association of TNF (rs1800629 and rs361525), TNFRSF1A (rs767455 and rs1800693), and TNFRSF1B (rs1061622 and rs3397) variants with COVID-19 severity, assessed as invasive mechanical ventilation (IMV) requirement, and the plasma levels of soluble TNF-α, TNFR1, and TNFR2 in patients with severe COVID-19. METHODS: The genetic study included 1353 patients. Taqman assays were used to assess the genetic variants. ELISA was used to determine soluble TNF-α, TNFR1, and TNFR2 in plasma samples from 334 patients. RESULTS: Patients carrying TT (TNFRSF1B rs3397) exhibited lower PaO2/FiO2 levels than those with CT + CC genotypes. Differences in plasma levels of TNFR1 and TNFR2 were observed according to the genotype of TNFRSF1B rs1061622, TNF rs1800629, and rs361525. According to the studied genetic variants, there were no differences in the soluble TNF-α levels. Higher soluble TNFR1 and TNFR2 levels were detected in patients with COVID-19 requiring IMV. CONCLUSIONS: Genetic variants in TNF and TNFRSFB1 influence the plasma levels of soluble TNFR1 and TNFR2, implicated in COVID-19 severity.

Entamoeba histolytica Trophozoites Interact with the c-Met Receptor at the Surface of Liver Origin Cells through the Gal/GalNAc Amoebic Lectin.

Amoebiasis in humans is caused by the protozoan parasite Entamoeba histolytica, which cytotoxic activity has been demonstrated on a wide variety of target cells. The process involves the adherence of the parasite to the cell, and such adherence is mediated by an amoebic surface lectin, known as Gal/GalNAc lectin. It is composed of heavy, intermediate, and light subunits. The carbohydrate recognition domain (CRD) has been identified within a cysteine-rich region in the lectin heavy subunit and has an amino acid sequence identity to the receptor-binding domain of hepatocyte growth factor (HGF). Recombinant CRD has been previously shown to compete with HGF for binding to the c-Met receptor IgG fusion protein. In the present study, we searched for evidence of interaction between the Gal/GalNAc lectin at the surface of trophozoites with the c-Met receptor expressed at the surface of HepG2 in coculture assays. Immunoprecipitation of the coculture lysate indicated interaction of the c-Met with a 60 kDa peptide recognized by antiamoebic lectin antibody. Colocalization of both molecules was detected by fluorescence confocal microscopy. Incubation of HepG2 cells with HGF before coculture with trophozoites prevents the cytotoxic effect caused by the parasites but not their adherence to the cells. Our results point to Gal/GalNAc lectin as a ligand of the c-Met receptor at the surface of HepG2 cells.

Th2-associated alternative Kupffer cell activation promotes liver fibrosis without inducing local inflammation.

Cirrhosis is the final outcome of liver fibrosis. Kupffer cell-mediated hepatic inflammation is considered to aggravate liver injury and fibrosis. Alternatively-activated macrophages are able to control chronic inflammatory events and trigger wound healing processes. Nevertheless, the role of alternative Kupffer cell activation in liver harm is largely unclear. Thus, we evaluated the participation of alternatively-activated Kupffer cells during liver inflammation and fibrosis in the murine model of carbon tetrachloride-induced hepatic damage. To stimulate alternative activation in Kupffer cells, 20 Taenia crassiceps (Tc) larvae were inoculated into BALBc/AnN female mice. Six weeks post-inoculation, carbon tetrachloride or olive oil were orally administered to Tc-inoculated and non-inoculated mice twice per week during other six weeks. The initial exposure of animals to T. crassiceps resulted in high serum concentrations of IL-4 accompanied by a significant increase in the hepatic mRNA levels of Ym-1, with no alteration in iNOS expression. In response to carbon tetrachloride, recruitment of inflammatory cell populations into the hepatic parenchyma was 5-fold higher in non-inoculated animals than Tc-inoculated mice. In contrast, carbon tetrachloride-induced liver fibrosis was significantly less in non-inoculated animals than in the Tc-inoculated group. The latter showed elevated IL-4 serum levels and low IFN-γ concentrations during the whole experiment, associated with hepatic expression of IL-4, TGF-ß, desmin and α-sma, as well as increased mRNA levels of Arg-1, Ym-1, FIZZ-1 and MMR in Kupffer cells. These results suggest that alternative Kupffer cell activation is favored in a Th2 microenvironment, whereby such liver resident macrophages could exhibit a dichotomic role during chronic hepatic damage, being involved in attenuation of the inflammatory response but at the same time exacerbation of liver fibrosis.

Entamoeba histolytica: oxygen resistance and virulence.

Entamoeba histolytica virulence has been attributed to several amoebic molecules such as adhesins, amoebapores and cysteine proteinases, but supporting evidence is either partial or indirect. In this work we compared several in vitro and in vivo features of both virulent E. histolytica (vEh) and non-virulent E. histolytica (nvEh) axenic HM-1 IMSS strains, such as complement resistance, proteinase activity, haemolytic, phagocytic and cytotoxic capacities, survival in mice caecum, and susceptibility to O(2). The only difference observed was a higher in vitro susceptibility of nvEh to O(2). The molecular mechanism of that difference was analyzed in both groups of amoebae after high O(2) exposure. vEh O(2) resistance correlated with: (i) higher O(2) reduction (O(2)(-) and H(2)O(2) production); (ii) increased H(2)O(2) resistance and thiol peroxidase activity, and (iii) reversible pyruvate: ferredoxin oxidoreductase (PFOR) inhibition. Despite the high level of carbonylated proteins in nvEh after O(2) exposure, membrane oxidation by reactive oxygen species was not observed. These results suggest that the virulent phenotype of E. histolytica is related to the greater ability to reduce O(2) and H(2)O(2) as well as PFOR reactivation, whereas nvEh undergoes irreversible PFOR inhibition resulting in metabolic failure and amoebic death.

IL-6 KO mice develop experimental amoebic liver infection with eosinophilia.

Interleukin 6 (IL-6) is a multifunctional cytokine that regulates various aspects of the immune response, such as acute phase reaction and hematopoiesis, and is an important signal that coordinates activities of liver cells, macrophages, and lymphocytes. Amoebic liver lesions have been studied, usually in hamsters, due to the problem of abscess development in mice. We report here the development of an experimental amoebic liver abscess (ALA) model in mice deficient in IL-6. Axenically grown amoebae were injected directly into the livers of C57BL/6 wild type (WT) and IL-6 KO -/- mice; the abscesses produced were counted and the inflammatory process was examined on 5, 10, and 20 days postinfection. Our results showed that IL-6 KO -/- mice develop ALA, in contrast to the WT strain, which usually do not have signs of abscess or infection. Histological analysis of the abscesses showed extended inflammatory response, mainly mediated by eosinophils, which strongly infiltrate the abscess in IL-6 K -/- mice. The present results suggest that in mice, IL-6 could play a role in the resistance against ALA.