[Clinical characteristics and prognosis of Staphylococcus aureus bacteremia]. / Características clínicas, pronóstico y factores asociados de la bacteriemia por Staphylococcus aureus en la actualidad.

OBJECTIVE: Staphylococcus aureus bacteremia patients characteristics at a tertiary hospital are described, and complications, mortality and associated factors are analyzed. METHODS: Data from patients with S. aureus bacteremia admitted between March 2020 and February2021 at Miguel Servet university hospital in Zaragoza were retrospectively analyzed. RESULTS: Results showed a 14 days mortality of 24.2% and an 30 days mortality of 40%. Overall survival decreased with complications appearance [HR 3.1 (1.2-8.05)] and age over 65 years [HR 3.1 (1.4-6.6)]. The adjusted analysis showed correlation between a higher mortality at 14 and 30 days with age over 65 years [OR 6.3 (1.7-23.1)], sepsis presence [OR 19.3 (5.4-68.7)] and number of positive (+) blood cultures ≥3 [OR 5.4 (0.8-34.1)]. Mortality at 14 days was associated with sepsis presence [OR 58.2 (5.7-592.9)], number of positive (+) blood cultures ≥3 [OR 14.1 (1.1-173.7)] and an older age [OR 1.1 (1.03-1.1)]. Analyzing time to positive blood cultures ≤12 hours and number of positive blood cultures ≥ 3 at the same time, frequency of sepsis increased [30 patients (66.6%) vs 15 patients (33.3%); OR 3.4 (IC95% 1.5-8)]. CONCLUSIONS: High 14- and 30-days mortality were found, as well as a worse evolution in older age patients, with sepsis presence, and with greater number of positive blood cultures and times to positive blood cultures ≤12 h.

[Impact of Staphylococcus aureus bacteremia in COVID-19 patients]. / Impacto de la bacteriemia por Staphylococcus aureus en pacientes con COVID-19.

OBJECTIVE: The disease caused by SARS-CoV-2 (COVID-19) has been a challenge for healthcare professionals since its appearance. Staphylococcus aureus has been described as one of the main pathogens causing bacterial infections in viral pandemics. However, co- infection with S. aureus causing bacteremia in patients with COVID-19 has yet to be well studied. METHODS: We performed a e study of S. aureus bacteremia (SAB) at Hospital Miguel Servet (Zaragoza) from March 2020 to February 2021. The clinical characteristics, mortality and risk factors of adults hospitalized patients with BSA associated COVID-19 compared to patients without COVID-19. RESULTS: A total of 95 patients with SAB were identified. 27.3% were positive for SARS-CoV-2. SAB represented 9.9% of bacteremia, being the second agent in frequency after E. coli. Nosocomial bacteremia was more frequent in the group of COVID-19 patients. The most frequent source of BSA in these patients was the respiratory source (26.9% vs 0%; P<0.001) followed by the skin (15.5% vs 15.9%; P=1). The development of sepsis was more frequent in COVID-19 patients (61,5% vs 7,8%; P=0,336) and among them, who received dexamethasone at doses > 6 mg/day (62.5% vs. 37.5%, P<0.05). CONCLUSIONS: Our data suggest that BSA has a negative impact on the evolution of patients with COVID-19. However, further and preferably prospective studies are required to obtain solid data on the impact of BSA on coronavirus patients.

[Evaluation of a rapid assay for detection of PBP2a Staphylococcus aureus]. / Evaluación de una prueba rápida para la detección de PBP2a en Staphylococcus aureus.

OBJECTIVE: Methicillin-resistant Staphylococcus aureus (MRSA) is a significant pathogen causing both healthcare-associated and community-acquired infection. Rapid and accurate detection of this pathogen is crucial for the use of appropriate antimicrobial therapy and the control of nosocomial spread. METHODS: A total of 107 S. aureus strains were assayed for methicillin resistance: Vitek2® (bioMérieux), CHROMagarTM MRSA II (BD Becton Dickinson), disk diffusion in agar for cefoxitin 30 µg and immunochromatography PBP2a SA Culture Colony Test (AlereTM). The results of conventional tests were compared with the "gold standard" PCR test for mecA gene. RESULTS: Sensitivity and specificity were: disk diffusion for cefoxitin 100% and 100% respectively, Vitek2® 100 and 100%, CHROMagarTM MRSA II 100 and 96%, and ICPBP2a detection 98,25% and 100%. CONCLUSIONS: ICPBP2a Culture Colony Test (AlereTM) is fast, efficient and economical technique for detection of penicillin binding protein 2a (PBP2a) from isolates. This assay is a useful tool for the management of hospital outbreaks.

Neuronal Transdifferentiation Potential of Human Mesenchymal Stem Cells from Neonatal and Adult Sources by a Small Molecule Cocktail.

Human mesenchymal stem cells (MSCs) are good candidates for brain cell replacement strategies and have already been used as adjuvant treatments in neurological disorders. MSCs can be obtained from many different sources, and the present study compares the potential of neuronal transdifferentiation in MSCs from adult and neonatal sources (Wharton's jelly (WhJ), dental pulp (DP), periodontal ligament (PDL), gingival tissue (GT), dermis (SK), placenta (PLAC), and umbilical cord blood (UCB)) with a protocol previously tested in bone marrow- (BM-) MSCs consisting of a cocktail of six small molecules: I-BET151, CHIR99021, forskolin, RepSox, Y-27632, and dbcAMP (ICFRYA). Neuronal morphology and the presence of cells positive for neuronal markers (TUJ1 and MAP2) were considered attributes of neuronal induction. The ICFRYA cocktail did not induce neuronal features in WhJ-MSCs, and these features were only partial in the MSCs from dental tissues, SK-MSCs, and PLAC-MSCs. The best response was found in UCB-MSCs, which was comparable to the response of BM-MSCs. The addition of neurotrophic factors to the ICFRYA cocktail significantly increased the number of cells with complex neuron-like morphology and increased the number of cells positive for mature neuronal markers in BM- and UCB-MSCs. The neuronal cells generated from UCB-MSCs and BM-MSCs showed increased reactivity of the neuronal genes TUJ1, MAP2, NF-H, NCAM, ND1, TAU, ENO2, GABA, and NeuN as well as down- and upregulation of MSC and neuronal genes, respectively. The present study showed marked differences between the MSCs from different sources in response to the transdifferentiation protocol used here. These results may contribute to identifying the best source of MSCs for potential cell replacement therapies.

Can Surgery Be Avoided? Exclusive Antibiotic Treatment for Pelvic Actinomycosis.

Pelvic actinomycosis is an uncommon, slowly progressing granulomatous infection that has been associated with the presence of intrauterine devices. Due to its unspecific clinical and radiologic findings, it can mimic pelvic or intra-abdominal malignancy leading to mutilating surgery of high morbidity. Rarely, diagnosis is made preoperatively and in most cases surgical intervention is necessary. The patient in our case is a 42-year-old female with an IUD for 15 years diagnosed with pelvic actinomycosis. Patient was uniquely diagnosed preoperatively through paracentesis and treated conservatively with prolonged antibiotic therapy and without any type of surgical intervention. Follow-up at 1 year showed almost complete radiologic resolution of the inflammatory mass, nutritional recovery, and absence of symptoms. Pelvic actinomycosis can be successfully diagnosed and treated medically without surgical interventions.

[Evaluation of an immunochromatographic test for the detection of OXA-48 carbapenemase]. / Evaluación de un ensayo inmunocromatográfico para la detección de carbapenemasa OXA-48.

OBJECTIVE: Detection and differentiation of various types of carbapenemases is crucial to their control and dissemination. OXA-48 is the most common carbapenemase in Spain and in our environment. The aim of this study is the evaluation of a new immunochromatographic test OXA-48 Card letitest (Coris, BioConcept Belgium) to detect this carbapenemase from solid media. METHODS: During the last year 151 strains of carbapenemase producing bacteria have been isolated, of which 136 were OXA-48 (126 Klebsiella pneumoniae, 1 Klebsiella oxytoca, 5 Escherichia coli, 4 Enterobacter cloacae), and 15 producing other carbapenemases . These 15 strains with other 73 carrying other resistance mechanisms (54 extended-spectrum ß-lactamases producers and 19 with other mechanisms) were used as negative controls. RESULTS: One hundred and thirty six strains carrying OXA-48 were positive with the test OXA-48 Card letitest and the 88 species used as controls were negative, resulting in a sensitivity and specificity of 100%. CONCLUSIONS: The OXA-48 Card letitest is simple, quick, safe and cheap (approx. 6€/test) and can be used in microbiology laboratories to confirm the production of OXA-48 carbapenemase in clinical isolates.

Contribution of MHC class I region to genetic susceptibility for giant cell arteritis.

OBJECTIVE: The aim of this study was to assess the potential contribution of HLA-class I MICA and HLA-B gene polymorphisms towards the pathogenesis of giant cell arteritis (GCA). METHODS: Ninety-eight biopsy-proven GCA patients and 225 ethnically matched controls from Lugo, Northwest Spain, were genotyped for the MICA-TM microsatellite polymorphism using a polymerase chain reaction (PCR)-based method. Genotyping of HLA-B was performed using PCR and detection with a reverse sequence-specific oligonucleotide (SSO) probes system. RESULTS: A significant difference in the distribution of the alleles of MICA between patient and control groups (P = 0.005) was found. This was due to an increased frequency of the MICA A5 allele in GCA patients compared with controls (26 vs 13.6%; P = 0.0001; P(C) = 0.0005; OR 2.2, 95% CI 1.4-3.4). In addition, the HLA-B*15 allele showed a higher frequency in GCA patients compared with controls (P = 0.004; P(C) = 0.04; OR 2.7, 95% CI 1.3-5.7). Interestingly, the association observed with the MICA A5 allele seems to be independent of linkage disequilibrium with HLA-B, as well as independent of that previously described with HLA-DRB1*04. Remarkably, simultaneous presence of MICA A5 and HLA-B*15 or HLA-DRB1*04 genetic markers leads to an increase in the OR obtained for each individual genetic marker (MICA A5 + B*15 OR 3.2; MICA A5 + DRB1*04 OR 5.8). CONCLUSIONS: Our results provide the first evidence that the MICA and HLA-B genes are independently associated with the genetic susceptibility to GCA, and suggest that several genes within the MHC might have independent effects in the susceptibility to this systemic vasculitis.

[Renal aging]. / Envejecimiento renal.

Frequently underestimated, the deterioration of the renal function characteristic of the aging has very prominent clinical consequences. In the present article some aspects of the cellular and molecular biology of this process are analysed. The critical role of the oxidative stress and of TGFbeta are underlined. Determinant genetic factors are also mentioned. Such a knowledge can contribute to develop therapeutical strategies to prevent the decline of the.renal function that happens with the aging.

CA microsatellite polymorphism of the nuclear factor kappa B1 gene in celiac disease.

In the present work, we investigate the possible effect of a CAn microsatellite polymorphism in the nuclear factor kappa B1 (NFKB1) gene on predisposition to celiac disease (CD). Seventy-eight Spanish families with CD were genotyped using a polymerase chain reaction (PCR)-fluorescent method, and the transmission patterns of different CAn alleles were analysed. Furthermore, in order to type the CAn polymorphism more accurately, samples between 126 and 144 bp were cloned and sequenced. A trend of association with the 132-bp allele was found (P = 0.02). This allele was more frequently transmitted to affected sibs, although the results of statistical tests were not significant after correction for multiple comparisons. After sequencing, we found that the 132-, 138- and 142-bp alleles had two As at the end of the CA microsatellite, with the other alleles presenting the described pattern (NCB1 nucleotide U60337) for the microsatellite repeats. These results suggest that the NFKB1 CAn microsatellite does not play a major role in CD susceptibility. In addition, a more detailed molecular characterization of the CA microsatellite is described.

Modulation of guanosine triphosphatase activity of G proteins by arachidonic acid in rat Leydig cell membranes.

Previous results from our group have indicated that arachidonic acid decrease cAMP production through a modification of heterotrimeric G proteins. In the present study, we have characterized the high affinity GTPase activity present in Leydig cell membranes and its regulation by fatty acids. The high-affinity GTPase activity, measured as [gamma32P] GTP hydrolysis rate, was both time and protein concentration dependent. Arachidonic acid elicited a dose-dependent inhibition of enzyme activity with an IC50 = 26.7+/-1.1 microM. The existence of only two double bonds in linoleic acid is reflected by a decrease in its inhibitory activity (IC50 = 34+/-2.3 microM). Saturated fatty acids showed no effect at this level. The kinetic analysis as interpreted by Lineweaver-Burk plots, indicated that 50 microM arachidonic acid had no effect on the apparent affinity for GTP, but resulted in a 40% decreases in the maximal velocity of the reaction. Arachidonic acid modulation of GTPase activity was not attenuated by blocking eicosanoid metabolism with inhibitors of 5'-lipoxygenase, cyclooxygenase, or epoxygenase P-450. The addition of arachidonic acid to pertussis toxin-treated membranes had no effect on the enzyme activity, indicating that arachidonic acid does not modify the GTPase activity present in Galphas protein. However, ADP-ribosylation with cholera toxin followed by arachidonic acid treatment led to a further 40% inhibition when compared with cholera toxin treatment alone. These results allowed us to postulate that arachidonic acid inhibits the GTPase activity of Gi protein family. To further analyze the mechanism of arachidonic acid inhibition of GTPase activity, the effect of arachidonic acid on the [35S]GTPgammaS binding was studied. No effect of this fatty acid on GTP binding was found. Combining our previous results with those found here, we can conclude that arachidonic acid maintains Gi proteins in their active state, which in turn inhibit adenylate cyclase and results in decrease cAMP levels.

Effects of muscle electrical stimulation on peak VO2 in cardiac transplant patients.

Peak oxygen consumption (peak VO2) has become a critical component in the evaluation of heart transplant recipients (HTR). In these patients, peak VO2 remains low after cardiac transplantation mainly because of persisting peripheral limitations in the working muscles. Muscular electrical stimulation, on the other hand, has been shown to enhance the oxidative capacity of healthy muscle. It was the purpose of our investigation to study the effects of ES on the peak VO2 of HTR. Fourteen (11 males and 3 females) HTR (age: 57+/-7yr, mean +/- SD; height: 163+/-7 cm, weight: 70.5+/-8.6 kg) were selected as subjects and each of them was randomly assigned to one of two groups: (a) group EXP (n = 7), receiving electrical stimulation on both quadriceps muscles during a period of 8 weeks, and (b) group CONT (n = 7), not receiving electrical stimulation. Before (PRE) and after (POST) the aforementioned 8-week period, respectively, all the subjects performed a cardiopulmonary exercise test (ramp protocol) on a cycle ergometer for peak VO2 determination. PRE values of peak VO2 were similar in both groups (17.1+/-2.0 vs 16.9+/-3.8ml x kg(-1) x min(-1) in EXP and CONT, respectively). However, peak values of VO2 significantly increased in EXP (p < 0.05) after the period of electrical stimulation (POST peak VO2: 18.7+/-2.0ml x kg(-1)), whereas no change was observed in CONT (POST peak VO2: 16.2+/-3.2 ml x kg(-1) x min(-1)). In conclusion, electrical stimulation could therefore be used to improve the functional capacity of HTR, and might be included in the rehabilitation programs of this population group.

Specific effect of arachidonic acid on 17beta-hydroxysteroid dehydrogenase in rat Leydig cells.

It is well known that arachidonic acid (AA) acts as an intratesticular factor regulating luteinizing hormone-mediated testicular steroidogenesis. The present studies were conducted to determine the effect of AA on steroidogenic enzymes in rat Leydig cells. Exogenously added AA significantly inhibited 22(R)-hydroxy-cholesterol-stimulated testosterone production, which is a clear indication that AA is acting at some point after cholesterol transport to the inner mitochondrial membrane. AA failed to block the conversion of 22(R)-hydroxycholesterol to pregnenolone, indicating that the cytochrome P-450 side-chain cleavage enzyme complex is not the site of inhibition. The present results demonstrate that only 17beta-hydroxysteroid dehydrogenase seems to be involved in the AA action, since nearly 60% inhibition of testosterone production was found when the cells were incubated with androstenedione. Furthermore, no effect of AA was found when androstenediol was used as substrate in the testosterone synthesis, which indicates that 3beta-hydroxysteroid dehydrogenase is not affected by AA. The conversion of AA to its metabolites is not required for its action on 17beta-hydroxysteroid dehydrogenase and the activation of protein kinase C is not involved in the inhibitory effect.

Different sites of action of arachidonic acid on steroidogenesis in rat Leydig cells.

The present study in purified rat Leydig cells shows that arachidonic acid may act as an intratesticular factor regulating LH-mediated testicular steroidogenesis. Arachidonic acid decreased, in a dose-dependent manner, the LH-stimulated cAMP and testosterone levels, over 2 h incubation. Incubation of Leydig cells with arachidonic acid did not modify 125I-hCG binding to the cells as compared to control, showing that the action of arachidonic acid is not related to a decrease of hCG binding to the cells. Forskolin-stimulated cAMP and testosterone production were inhibited by 51.65 and 70.9%, respectively, in the presence of arachidonic acid (100 microM), although the ED50 for the diterpene was not changed. When isobutyl-methyl-xanthine was added to the incubation medium, the same percentage of inhibition was found indicating that arachidonic acid inhibition of cAMP production is not due to stimulation of Leydig cell phosphodiesterase activity. Pretreatment of the cells with pertussis toxin, to inactivate Gi, was also without effect on arachidonic acid inhibition of LH-stimulated cAMP production, but pertussis toxin abolished the inhibitory effects of arachidonic acid when adenylate cyclase was stimulated with forskolin. However, arachidonic acid addition resulted in inhibition of LH- and forskolin-stimulated testosterone production, even if the cells were pretreated with pertussis toxin. It can be concluded that: (1) The inhibitory effect of arachidonic acid is neither due to a decrease of hCG binding to Leydig cells nor to a stimulation of cell phosphodiesterase activity; (2) arachidonic acid modulates cAMP production at two different levels, either by activation of Gi protein and by inhibition of Gs protein or adenylate cyclase; (3) the effect of arachidonic acid on steroidogenesis is also beyond cAMP formation.

[Bilateral multilobular cystic adenomatoid malformation]. / Malformación adenomatoidea quística multilobular bilateral.

We reported a case of bilateral and multilobar Congenital Cystic Adenomatoid Malformation (C.C.A.M.) in a four months old child with good clinical results after resections of the lesions. This is a relatively rare form of pulmonary illness. The final prognosis, in those patients, depends on the type of malformation, the presence or absence of fetal hydrops and on the degree of affected lung. There have been reported a few cases of multiple affectation. We will consider the physiopathological aspects of the case, late clinical presentation and treatment and the positive surgical response based in the findings of the functional and anatomic imagen studys.