MIF is a common genetic determinant of COVID-19 symptomatic infection and severity.

BACKGROUND: Genetic predisposition to coronavirus disease 2019 (COVID-19) may contribute to its morbidity and mortality. Because cytokines play an important role in multiple phases of infection, we examined whether commonly occurring, functional polymorphisms in macrophage migration inhibitory factor (MIF) are associated with COVID-19 infection or disease severity. AIM: To determine associations of common functional polymorphisms in MIF with symptomatic COVID-19 or its severity. METHODS: This retrospective case-control study utilized 1171 patients with COVID-19 from three tertiary medical centers in the USA, Hungary and Spain, together with a group of 637 pre-pandemic, healthy control subjects. Functional MIF promoter alleles (-794 CATT5-8,rs5844572), serum MIF and soluble MIF receptor levels, and available clinical characteristics were measured and correlated with COVID-19 diagnosis and hospitalization. Experimental mice genetically engineered to express human high- or low-expression MIF alleles were studied for response to coronavirus infection. RESULTS: In patients with COVID-19, there was a lower frequency of the high-expression MIF CATT7 allele when compared to healthy controls [11% vs. 19%, odds ratio (OR) 0.54 [0.41-0.72], P < 0.0001]. Among inpatients with COVID-19 (n = 805), there was a higher frequency of the MIF CATT7 allele compared to outpatients (n = 187) (12% vs. 5%, OR 2.87 [1.42-5.78], P = 0.002). Inpatients presented with higher serum MIF levels when compared to outpatients or uninfected healthy controls (87 ng/ml vs. 35 ng/ml vs. 29 ng/ml, P < 0.001, respectively). Among inpatients, circulating MIF concentrations correlated with admission ferritin (r = 0.19, P = 0.01) and maximum CRP (r = 0.16, P = 0.03) levels. Mice with a human high-expression MIF allele showed more severe disease than those with a low-expression MIF allele. CONCLUSIONS: In this multinational retrospective study of 1171 subjects with COVID-19, the commonly occurring -794 CATT7MIF allele is associated with reduced susceptibility to symptomatic SARS-CoV-2 infection but increased disease progression as assessed by hospitalization. These findings affirm the importance of the high-expression CATT7MIF allele, which occurs in 19% of the population, in different stages of COVID-19 infection.

Autoimmune progesterone dermatitis: a complex case

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Metástasis cutáneas a distancia en el cáncer de mama: presentación de un caso / No disponible

La aparición de lesiones cutáneas aparentemente benignaspuede traducirse en un signo de enfermedad sistémica en pacientesoncológicos. En mujeres, el cáncer de mama es el quecon mayor frecuencia metastatiza en la piel, a nivel locorregional,siendo excepcionales y de mal pronóstico las lesiones cutáneasa distancia. Presentamos el caso de una paciente tratadade un cáncer de mama, que presenta metástasis en piel ytejido celular subcutáneo tras un periodo de dos años libre deenfermedad(AU)

Benign-like skin lesions could be a sign of systemic diseasein oncologic patients. In women breast cancer is the tumorwhich develops loco-regional skin metastases more frequently,being exceptional and a poor prognostic factor the presenceof distant skin lesions. We present a clinical case of a treatedbreast cancer’s woman, who shows skin metastases after twoyears free of disease(AU)

Estudio de validación de la linfogammagrafía y biopsia del ganglio centinela en cáncer de mama / Validation study of the lymphadenectomy and sentinel node biopsy in the breast cancer

Objetivo: La afectación de los ganglios axilares constituyeel principal factor pronóstico en cáncer de mama en cuantosupervivencia global. El propósito de este trabajo es el de presentarlos resultados de la primera fase de realización de labiopsia del ganglio centinela en cáncer de mama en nuestrocentro.Métodos: Se incluyó un total de 50 pacientes a las que serealizó la biopsia del ganglio centinela, seguida de linfadenectomíade los niveles I y II. Las indicaciones fueron tumor inferiora 2,5 cm de diámetro sin sospecha de afectación axilar,pacientes con carcinoma ductal in situ extenso y sin quimioterapiaprevia.Resultados: La tasa de detección general fue del 98%.Hubo un falso negativo. Se encontraron micrometástasis entres pacientes.Conclusión: La biopsia del ganglio centinela es un métodofiable para determinar el estado de los ganglios linfáticosregionales en pacientes con cáncer de mama

Objective: The status of the axilla is the single most importantprognostic indicator of overall survival in patients withbreast cancer. The aim of this study was to validate sentinelnode biopsy for axillary staging after the initial learning phase.Methods: A total of 50 patients, who had standard sentinelnode biopsy followed by level I and II axillary clearance,were recruited prospectively. Accepted indications were tumorless than 2,5 cm without suspicious findings in the axilla, patientswith large ductal carcinoma in situ and patients withoutpreoperative chemotherapy.Results: The overall detection rate was 98 per cent. Therewas one false negative. Micrometastases were found in threepatients.Conclusion: The sentinel node biopsy is a reliable methodfor determining the status of the regional lymph nodes in patientswith breast cancer

Brucella lipopolysaccharides induce cyclooxygenase-2 expression in monocytic cells.

Human brucellosis is characterized by the presence of both acute inflammatory episodes and chronic inflammation with granuloma formation. On this basis, the proinflammatory effects of smooth lipopolysaccharide of Brucella (S-LPS) were addressed and compared to those of LPS from Escherichia coli. For this purpose, the induction of cyclooxygenase-2 (COX-2), the production of the chemokine monocyte chemoattractant protein-1 (MCP-1), and the activation of the nuclear factor kappa B (NF-kappa B) were studied. S-LPS was found to induce both COX-2 expression and MCP-1 production; however, the potency of E. coli LPS exceeded that of Brucella S-LPS by some orders of magnitude. However, at concentrations above 1 microg/ml, all of the LPS produced comparable effects, including their ability to activate the NF-kappa B system. These observations help explain the inflammatory events associated with Brucella infection and the ability of Brucella to produce monocyte recruitment and granuloma formation.

Infecciones por bartonella

Las infecciones humanas por microorganismos del género Bartonella se implican en la etiología de enfermedades pertenecientes a dos grandes grupos, por una parte cuadros conocidos desde hace mucho tiempo (verruga peruana, fiebre de las trincheras, enfermedad por arañazo de gato) y, por otra, entidades clínicas de descubrimiento reciente, cuyo espectro se ha ampliado a lo largo de la última década como, angiomatosis y peliosis bacilar, septicemias y endocarditis (AU)

Specificity of a polymerase chain reaction assay of a target sequence on the 31-kilodalton Brucella antigen DNA used to diagnose human brucellosis.

The aim of this study was to evaluate the specificity of a polymerase chain reaction assay for detecting Brucella DNA using primers specific for the amplification of a 223 bp region of the sequence encoding a 31 kDa immunogenic Brucella abortus protein (BCSP31). DNA from all Brucella strains, including type, reference, vaccine and field strains, were correctly amplified. With the exception of Ochrobactrum spp., no other amplification was detected with a broad panel of microorganisms serologically or phylogenetically related to Brucella spp. This very good degree of specificity, together with its high yield demonstrated in previous clinical studies, confirms that this polymerase chain reaction assay could be a useful tool for the diagnosis of human brucellosis.

Hydatid cyst of the lung: diagnosis and treatment.

Hydatid infestation of the lung can be primary or secondary. In three of four cases the cyst is a single one. Hydatidosis of a different location, particularly the liver, may be associated. The period of initial growth of primary hydatidosis is frequently asymptomatic. Bronchial fistulization is an important event in the evolution of the cyst. Intrapleural rupture constitutes a rare eventuality, but it is often as characteristic as it is severe. Secondary, metastatic hydatidosis, due to breaking of a primary visceral cyst in a vein or heart, is rare. A special form is so-called multiple malignant pulmonary hydatidosis, which causes progressive respiratory deficiency and right ventricular failure. There are a variety of radiographic images. Ultrasonography, computed tomography, and magnetic resonance imaging can recognize certain details of the lesions and discover others that are not visible by conventional radiography. For a specific serologic diagnosis, our experience favors the immunoglobulin G enzyme-linked immunosorbent assay and immunoelectrophoresis. Treatment is essentially surgical. In general, chemotherapy is used as a complement to operative treatment to avoid recurrence. Surgery has two objectives: to remove the parasite and to treat the bronchipericyst pathology and other associated lesions. The prognosis has changed during the last few years, and results are now commonly satisfactory. The most frequent complications are pleural infection and prolonged air leakage. Operative mortality does not exceed 1% to 2%. Despite the low mortality and the limited recurrence rate, it is necessary to remember the invading character of pulmonary hydatid disease, which sometimes makes therapy difficult and questionable. Prophylaxis is essential to eradicate the disease completely.

Comparative sensitivity of six serological tests and diagnostic value of ELISA using purified antigen in hydatidosis.

Most serodiagnostic techniques have been evaluated for diagnosis of cystic hydatid disease caused by Echinococcus granulosus. Each, to varying degrees, has been shown to give false results, with considerable variation between laboratories. The comparative study was made concerning the sensitivity of the immunodiagnostic methods based on 58 sera from hydatid disease with different cyst locations. Latex agglutination, immunoelectrophoresis (IEP), and specific IgE, IgG enzyme-linked immunosorbent assay (ELISA) tests were studied. Specific IgG ELISA AgB (antigen B-rich fraction) was the most sensitive test (96.5%) and the least sensitive tests were specific IgE ELISA (24.1%) and IEP (25.8%). The low sensitivity of these two tests was due partly to the low reactivity detected in the sera of patients with lung hydatidosis. Initial laboratory studies showed purified antigens to be preferable to crude cyst fluid, regardless of the type of test used. For this reason, we evaluated the sensitivity and specificity of ELISA by using the purified antigen-B-rich fraction. In all, 117 sera were examined: 78 sera from patients with hydatidosis surgically confirmed, 15 sera from healthy control subjects, and 24 sera from patients with diseases other than hydatidosis. The method gave good results: 93.5% sensitivity, 89.7% specificity, and 92.3% diagnostic efficacy.

Evaluation of an immunocapture-agglutination test (Brucellacapt) for serodiagnosis of human brucellosis.

We evaluated the validity and the usefulness of a new test for the diagnosis of human brucellosis based on an immunocapture-agglutination technique. A total of 315 sera from 82 patients with a diagnosis of brucellosis, 157 sera from patients in whom brucellosis was suspected but not confirmed, and 412 sera from people living in rural areas with endemic brucellosis were studied. The seroagglutination test (SAT), Coombs anti-Brucella test, and Brucellacapt test were evaluated. All the initial sera from the 82 patients proved to be positive in Brucellacapt and Coombs tests, while only 75 (91.4%) were positive in the SAT. If a >/=1/160 diagnostic threshold titer was defined for the Brucellacapt test, Coombs test, and SAT, the sensitivities were 95.1, 91.5, and 65.8%, respectively. Taking the same diagnostic threshold titer for the 157 sera from the unconfirmed but suspected patients, the specificities of the Brucellacapt, Coombs, and SAT were 81.5, 96.2, and 100%, respectively; for the 412 control sera, the specificities were 99.0, 99.8, and 100%. The diagnostic efficiency (area below the receiver operating characteristic curve) of Brucellacapt was 0.987852 (95% confidence interval [CI], 0.95109 to 0.99286), very similar to the diagnostic efficiency of the Coombs test (0.97611; 95% CI, 0.94781 to 0.99146) and higher than that of SAT (0.91013; 95% CI, 0.86649 to 0.94317). The results of the Brucellacapt test were compared with those of the Coombs test (correlation coefficient, 0.956; P = 0.000) and SAT (correlation coefficient, 0.866; P = 0.000). The study shows very good correlation between the Brucellacapt and Coombs tests, with a high concordance between titers obtained in the two tests. Nevertheless, lower correlation and concordance were found between the Brucellacapt and Coombs tests when the results for titers of >/=1/160 were compared (0.692; P = 0.000). In acute brucellosis, the Brucellacapt and Coombs tests render positive titers of >/=1/160. When the titers are lower, they increase significantly in the following 30 days, despite the evolution of SAT titers. In contrast, Brucellacapt and Coombs titers are always high (>/=1/640) in brucellosis with long evolution, whether SAT titers are higher or lower than 1/160.

[Laboratory diagnosis and serologic course in patients with tularemia]. / Diagnóstico de laboratorio y evolución serológica de pacientes con tularemia.

BACKGROUND: Tularemia was practically unknown in Spain until the end of 1997, when an epidemic outbreak was declared. This paper presents the data on microbiological diagnosis of 55 patients who suffered from tularemia. PATIENTS AND METHODS: Thirty-two samples from 19 patients and 151 serum samples from 55 patients were obtained for culture. Serologic diagnosis was performed by tube sero-agglutination and microagglutination. Three types of tests were performed on all sera: Wright sero-agglutination (WSA), Coombs test against Brucella spp. and sero-agglutination against Yersinia enterocolitica O:3, Yersinia enterocolitica O:3, and Proteus OX 19. RESULTS: F. tularensis was found in two samples (6.25%) of the 32 received. Titers > or = 1/160 were obtained in 78.2% and 74.5% of the initial sera by tube sero-agglutination and microagglutination, respectively. Correlation between the two tests was 0.80 (p < 0.001). Prozone phenomenon was observed in 59.9% of the sera, while crossed reactivity to Brucella spp. and Proteus spp. was found in 9.3% and 22.8%, respectively. No crossed reactivity was observed with Yersinia spp. CONCLUSIONS: Culture of F. tularensis has low sensitivity. The correlation obtained between tube sero-agglutination and microagglutination is good. Both techniques are useful in routine diagnosis of tularemia, although microagglutination has some advantages over tube agglutination.

Lipopolysaccharides of Brucella abortus and Brucella melitensis induce nitric oxide synthesis in rat peritoneal macrophages.

Smooth lipopolysaccharide (S-LPS) and lipid A of Brucella abortus and Brucella melitensis induced the production of nitric oxide (NO) by rat adherent peritoneal cells, but they induced lower levels of production of NO than Escherichia coli LPS. The participation of the inducible isoform of NO synthase (iNOS) was confirmed by the finding of an increased expression of both iNOS mRNA and iNOS protein. These observations might help to explain (i) the acute outcome of Brucella infection in rodents, (ii) the low frequency of septic shock in human brucellosis, and (iii) the prolonged intracellular survival of Brucella in humans.

Clinical evaluation of a commercial ligase-based gene amplification method for detection of Mycobacterium tuberculosis.

The purpose of this study was to evaluate the clinical usefulness of a commercial ligase-based gene amplification method (LCx Mycobacterium tuberculosis test; Abbott Laboratories, USA) for detection of Mycobacterium tuberculosis. The tuberculosis infection rate among clinical samples was 10.6%. The sensitivity, specificity, and positive and negative predictive values were 23.5%, 100%, 100%, and 91.7%, respectively, with the fluorochrome auramine stain; 32.4%, 100%, 100%, and 92.6%, respectively, with culture; and 76.5%, 95.8%, 68.4% and 97.2%, respectively, with the gene amplification method. When only samples from patients without current or previous treatment were studied, the sensitivity was 36.4% with the auramine stain, 63.6% with culture, and 100% with the gene amplification assay. The mean treatment time for culture-negative and assay-negative samples was greater than that of culture-negative and assay-positive samples. The LCx Mycobacterium tuberculosis test is a sensitive method for detection and identification of Mycobacterium tuberculosis. It produces few false-positive results. However, as it can remain positive after the culture becomes negative, it is not recommended for evaluation of treatment efficiency.

[Genotypes of hepatitis C virus: their relationship with risk factors, the severity of liver disease, and the serologic response]. / Genotipos del virus de la hepatitis C: relación con los factores de riesgo, con la gravedad de la enfermedad hepática y con la respuesta serológica.

BACKGROUND: The objective of our study was to ascertain the prevalence of different HCV genotypes between the hepatitis C patients in the health area of Monforte de Lemos, Spain, as well as the possible influence of risk factors on their distribution and their relation with hepatic disease and with the serologic response. PATIENTS AND METHODS: We have studied 128 patients with hepatitis C. Of these, 41 were intravenous drug users (IVDU), 19 had received transfusions, 7 were hemodialyzed and in 61 the risk factors were unknown. Antibodies against HCV were detected by second-generation enzyme immunoassay (EIA) and confirmed by immunoblot. RNA-HCV presence was studied by reverse transcription-PCR (RT-PCR), and a reverse hybridization test of the amplifications was used for the genotyping. RESULTS: Hepatitis C genotypes 1b (46.1 [8.6%]), 1a (23.4 [7.3%]) and 3a (13.3 [5.9%]) were the most frequently encountered genotype. Genotype 1a (48.8 [15.3%]) was the most prevalent genotypes in IVDU patients, while 1b was the most frequent in patients of unknown risk factors (62.3 [12.1%]). Alanine-aminotransferase (ALT) was elevated in 66.6 (17.7%) of patients with genotype 1a, in 87.5 (8.6%) of patients with genotype 1b (p = 0.0367) and in 94.1 (11.2%) of patients with genotype 3a (p = 0.0347). Subtype 1b was present in 6 of 7 cases of cirrhosis (85.7%) and in 7 of 12 cases of active chronic hepatitis (58.3%). No significant statistical differences were observed between the genotypes and the specific IgM response against core antigen of HCV, neither we observed differences in the serologic response against C1, C2, NS3 and NS4 peptides. CONCLUSIONS: Hepatitis C genotypes 1a and 3a were the most prevalent genotypes between IVDU patients while genotype 1b was the most frequent between non-IVDU patients. Genotype 1b was associated to severe liver disease. Percentage of positivity or the reactivity against HCV peptides was independent of the genotype encountered in the patient.

[Variants of hepatitis C virus in different risk groups. Comparative study of a method for genotyping and another for serotyping]. / Variantes del virus de la hepatitis C en diferentes grupos de riesgo. Estudio comparativo de un método de genotipificación y otro de serotipificación.

AIMS: The aim of this study was to know the prevalence of the different variants of HCV in the Health Care area of Monforte de Lemos (Lugo, Spain) and its distribution according to risk factors and to compare the results obtained with one genotyping and one serotyping technique. PATIENTS AND METHODS: Eighty-four patients with hepatitis C were studied, 25 of whom were IVDA, 14 had received blood transfusions, 4 hemodialysis and the risk factor was unknown in 41. The antibodies against HCV were studied by second generation EIA and confirmed by an immunoblot technique. Serotyping was carried out by an ELISA test. Genotyping was undertaken with a reverse hybridation test of the amplification obtained by polymerase chain reaction prior to reverse transcription (RT-PCR). RESULTS AND CONCLUSIONS: The genotypes most frequently observed were 1b (47.6%), 1a (20.2%) and 3 (14.3%). In the IVDA patients the genotypes 1a (40%) and 3 (24%) predominated. The 1b genotype was the most prevalent in the patients of unknown risk (68.3%) and patients with a history of blood transfusion (50%). The prevalence of the different serotypes was similar to that of the corresponding genotypes, with nearly 100% agreement. The number of untypable cases was greater in the serotyping technique (20.2%) than in the genotyping (2.4%). A greater number of mixed infections was detected with serotyping (7 cases, 8.3%) than with genotyping (1 case, 1.2%). Lesser sensitivity of the serotyping test was observed in the patients lacking anti-NS4 antibodies.

Relation of hepatitis C virus genotypes to risk factors and hepatic disease in Spanish patients.

OBJECTIVE: To ascertain the prevalence of hepatitis C virus (HCV) genotypes in Spain and their distribution by risk factors. METHODS: The study covered 216 patients with hepatitis C. Of these, 63 were intravenous drug users (IVDU), 44 had received transfusions, and 30 were hemodialyzed, and in 79 the risk factors were unknown. Antibodies against HCV were detected by second-generation enzyme immunoassay (EIA) and confirmed by immunoblot. HCV RNA presence was investigated by reverse transcription---polymerase chain reaction (RT-PCR), and a reverse hybridization test of the amplifications was used for the genotyping. RESULTS: The most frequently encountered genotypes were 1b (48.1%), 1a (21.3%) and 3a (11.1%). HCV genotypes 1a (42.8%) and 3a (20.6%) were the most prevalent genotypes in IVDU patients, while 1b was the most frequent in patients with unknown risk factors (62.0%), transfused patients (68.1%) and hemodialyzed patients (50.0%). Mixed infections were detected in nine cases (4.1%); three appeared in IVDU patients (4.7% of the total IVDUs), two in transfused patients (4.5%) and four (50%) in patients with unknown risk factors. No statistically significant differences were found in average ages of the IVDU patients with different genotypes. Non-IVDU patients having genotype 3a presented the lowest average age of all. No significant statistical differences were observed in alanine aminotransferase levels among patient groups with different genotypes (p>0.05 in all cases). Subtype 1b was present in six of the seven cases of cirrhosis (85.7%) and in nine of the 18 cases of active chronic hepatitis (50.0%).