Fluconazole-resistant Candida parapsilosis genotypes from hospitals located in five Spanish cities and one in Italy: Description of azole-resistance profiles associated with the Y132F ERG11p substitution.

BACKGROUND: Fluconazole-resistant Candida parapsilosis is a matter of concern. OBJECTIVES: To describe fluconazole-resistant C. parapsilosis genotypes circulating across hospitals in Spain and Rome and to study their azole-resistance profile associated with ERG11p substitutions. PATIENTS/METHODS: We selected fluconazole-resistant C. parapsilosis isolates (n = 528 from 2019 to 2023; MIC ≥8 mg/L according to EUCAST) from patients admitted to 13 hospitals located in five Spanish cities and Rome. Additionally, we tested voriconazole, posaconazole, isavuconazole, amphotericin B, micafungin, anidulafungin and ibrexafungerp susceptibility. RESULTS: Of the 53 genotypes found, 49 harboured the Y132F substitution, five of which were dominating city-specific genotypes involving almost half the isolates. Another genotype involved isolates harbouring the G458S substitution. Finally, we found two genotypes with the wild-type ERG11 gene sequence and one with the R398I substitution. All isolates were fully susceptible/wild-type to amphotericin B, anidulafungin, micafungin and ibrexafungerp. The azole-resistance patterns found were: voriconazole-resistant (74.1%) or voriconazole-intermediate (25.2%), posaconazole-resistant (10%) and isavuconazole non-wild-type (47.5%). Fluconazole-resistant and voriconazole non-wild-type isolates were likely to harbour substitution Y132F if posaconazole was wild type; however, if posaconazole was non-wild type, substitution G458S was indicated if isavuconazole MIC was >0.125 mg/L or substitution Y132F if isavuconazole MIC was ≤0.125 mg/L. CONCLUSIONS: We detected a recent clonal spread of fluconazole-resistant C. parapsilosis across some cities in Spain, mostly driven by dominating city-specific genotypes, which involved a large number of isolates harbouring the Y132F ERG11p substitution. Isolates harbouring substitution Y132F can be suspected because they are non-susceptible to voriconazole and rarely posaconazole-resistant.

Progressive multifocal leukoencephalopathy: a retrospective study of the last 12 years in a tertiary-care hospital.

Our study aims to report on the demographic, incidence rate (IR), clinical, and microbiological characteristics of PML patients diagnosed in our tertiary-care hospital over the past 12 years. In this retrospective observational study, we reviewed all requests for JCPyV PCR in CSF from patients with suspected PML. We collected demographic, clinical, and microbiological data of patients diagnosed with PML. Since 2018, real-time quantitative PCR has been used, whereas prior to 2018, samples were sent to our National Reference Center for qualitative diagnosis. Thirteen patients were diagnosed with PML, with 10 of them having a definitive diagnosis and 3 classified as a possible diagnosis with negative PCR results. Eleven patients had advanced HIV, one had non-Hodgkin's lymphoma, and one had systemic lupus erythematosus. Most of the white matter lesions were located at the cerebral level, although the parenchyma and cerebellum were also affected. The most frequent symptoms were behavioral disorders and hemiparesis. The viral load of JCPyV in cerebrospinal fluid was < 1000 copies/mL in three patients. Six patients received compassionate treatment, and all six patients with definitive PML diagnosis died. Although advanced HIV patients were the most affected by PML in our study, it should also be considered in patients with other underlying diseases. While current PCR tests offer high sensitivity and specificity, false negatives can occur. The prognosis of the disease remains poor, and early multidisciplinary diagnosis-including clinical, microbiological, and neuroimaging assessments-remains crucial for improving neurological damage and prognosis.

A Tale of Two Hospitals: Comparing CAPA Infections in Two ICUs During the Spanish Fourth Pandemic Wave.

PURPOSE: COVID-19 associated pulmonary aspergillosis (CAPA) is a new clinical entity linked to SARS-CoV-2 infection that is causing a rise on the risk of complications and mortality, particularly in critical patients. METHODS: We compared diagnostic and clinical features in two cohorts of patients with severe COVID-19 admitted in the intensive care units (ICU) of two different hospitals in Madrid, Spain, between February and June 2021. Clinical and microbiological relevant aspects for CAPA diagnosis were collected for further classification. CAPA was classified as colonization, possible, probable, proven, and tracheobronchial aspergillosis according to the ECMM/ISHAM consensus, with some modifications to consider tracheobronchial aspirate as sample comparable to non-bronchoscopic lavages (NBL). RESULTS: 56 patients admitted in HULP (Hospital Universitario La Paz) ICU and 61 patients admitted in HEEIZ (Hospital de Emergencias Isabel Zendal) ICU had clinical suspicion of invasive fungal disease in the context of COVID-19 infection. Cultures were positive for Aspergillus spp. in 32 patients. According to 2020 European Confederation of Medical Mycology and the International Society for Human and Animal Mycology (ECMM/ISHAM) consensus, 11 patients were diagnosed with possible CAPA and 10 patients with probable CAPA. Global incidence for CAPA was 6.3%. Global median days between ICU admission and diagnosis was 14 day. Aspergillus fumigatus complex was the main isolated species. Antifungal therapy was used in 75% of patients with CAPA suspicion, with inter-hospital differences in the administered antifungals. Global overall mortality rate for CAPA patients was 66.6% (14/21). All-cause mortality in non-CAPA cohorts were of 26.3% in HULP group (34/129) and 56.8% (104/183) in HEEIZ group. CONCLUSIONS: There were no significant differences in incidence between the two hospitals, and differences in antifungal therapy did not correlate with differences in mortality, reflecting that both first-line azoles and Amphotericin B could be effective in treating CAPA infections, according to the current guideline indications.

Pacemaker pocket infection by Nocardia carnea. First case description and literature review.

Acid-fast gram-positive bacilli are a seldom causal agent of cardiac implantable electronic devices (CIED) infections. A pacemaker pocket infection by Nocardia carnea is presented. The objective of this review is to know the incidence of pacemaker pocket infection by Nocardia and to collect information to contribute to the management of this infection. We describe both our case and those found in the literature. Only three cases were found. Two of the patients were older than 70 years without immunosuppression, presenting erythema at the pacemaker implantation site as main symptom. Bloodstream infection was registered in one of them. Three microorganisms were sensitive to cotrimoxazole. The minimum time of antibiotic therapy was 6 weeks. An incomplete device removal was done in one case, resulting in an unfavorable clinical course. The incidence of pacemaker pocket infection by these microorganisms is low, resolved in most cases with antibiotic treatment and device removal.

Clinitest rapid COVID-19 antigen test for the diagnosis of SARS-CoV-2 infection: A multicenter evaluation study.

OBJECTIVES: RT-PCR assay is the reference method for diagnosis of COVID-19, but it is also a laborious and time-consuming technic, limiting the availability of testing. Rapid antigen-detection tests are faster and less expensive; however, the reliability of these tests must be validated before they can be used widely. The objective of this study was to determine the performance of the Clinitest Rapid COVID-19 Antigen Test (ClinitestRT) (SIEMENS) for SARS-CoV-2 in nasopharyngeal swab specimens. METHODS: This prospective multicenter study was carried out in three Spanish university hospitals including individuals with clinical symptoms or epidemiological criteria for COVID-19. Only individuals with ≤7 days from the onset of symptoms or from exposure to a confirmed case of COVID-19 were included. Two nasopharyngeal samples were taken to perform the ClinitestRT, as a point-of-care test, and a diagnostic RT-PCR test. RESULTS: Overall sensitivity and specificity for the ClinitestRT among the 450 patients studied were 93.3% (CI 95%: 89.7-96.8) and 99.2% (CI 95%: 97.2-99.8), respectively. Sensitivity in participants with ≤5 days of the clinical course was 93.6% (CI 95%: 89.2-96.3), and in participants who had a CT < 25 for the RT-PCR test was 98.4% (CI 95%: 94.5-99.6). Agreement between techniques was 96.7% (kappa score: 0.93; CI 95%: 0.90-0.97). CONCLUSIONS: The ClinitestRT provides good clinical performance, with more reliable results for patients with a higher viral load. The results must be interpreted based on the local epidemiological context.

Think of the Children: Evaluation of SARS-CoV-2 Rapid Antigen Test in Pediatric Population.

BACKGROUND: Real-time reverse transcription-quantitative polymerase chain reaction (RT-qPCR) is the reference laboratory method to diagnose SARS-CoV-2 infection then requires equipment and is time-consuming. There is a crucial demand for rapid techniques such as antigen detection test. Considering the different diagnostic accuracy of tests with other respiratory viruses in adults and children, SARS-CoV-2 antigen test must be evaluated specifically in children. METHODS: The purpose of this study was to evaluate the performance of Panbio COVID-19 Ag Rapid Test Device (Abbott) as a point-of-care test for diagnosis of SARS-CoV-2 in comparison to RT-qPCR in a pediatric population. RESULTS: Four hundred forty nasopharyngeal swabs were tested. Amongst the 18 positive RT-qPCR samples, 14 were detected by the rapid antigen test, given an overall sensitivity of 77.7%. All the samples detected positive with the antigen rapid test were also positive with RT-qPCR. CONCLUSION: The sensitivity of Panbio COVID-19 Ag Rapid Test Device is lower in children than in adults. Nevertheless, considering the good values of specificity, negative and positive predictive values this test could be used as a frontline test to obtain quick results, although the negative values with COVID-19 high clinical suspicion should be confirmed using RT-qPCR.

Multicenter evaluation of the Panbio™ COVID-19 rapid antigen-detection test for the diagnosis of SARS-CoV-2 infection.

OBJECTIVES: The standard RT-PCR assay for coronavirus disease 2019 (COVID-19) is laborious and time-consuming, limiting testing availability. Rapid antigen-detection tests are faster and less expensive; however, the reliability of these tests must be validated before they can be used widely. The objective of this study was to determine the performance of the Panbio™ COVID-19 Ag Rapid Test Device (PanbioRT) (Abbott) in detecting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in nasopharyngeal swab specimens. METHODS: This prospective multicentre study was carried out in ten Spanish university hospitals and included individuals with clinical symptoms or epidemiological criteria of COVID-19. Only individuals with ≤7 days from the onset of symptoms or from exposure to a confirmed case of COVID-19 were included. Two nasopharyngeal samples were taken to perform the PanbioRT as a point-of-care test and a diagnostic RT-PCR test. RESULTS: Among the 958 patients studied, 325 (90.5%) had true-positive results. The overall sensitivity and specificity for the PanbioRT were 90.5% (95%CI 87.5-93.6) and 98.8% (95%CI 98-99.7), respectively. Sensitivity in participants who had a threshold cycle (CT) < 25 for the RT-PCR test was 99.5% (95%CI 98.4-100), and in participants with ≤5 days of the clinical course it was 91.8% (95%CI 88.8-94.8). Agreement between techniques was 95.7% (κ score 0.90; 95%CI 0.88-0.93). CONCLUSIONS: The PanbioRT performs well clinically, with even more reliable results for patients with a shorter clinical course of the disease or a higher viral load. The results must be interpreted based on the local epidemiological context.

Cocaine exposure during pregnancy and postpartum maternal behavior in mice / Cocaína durante a Gestação e Comportamento Materno Pós-parto em Ratos / Cocaína durante la gestación y conducta materna postparto en ratones

Abstract Maternal cocaine abuse during pregnancy is associated to neglect, abuse, and mother-child bond disruption, which directly affects infant development; therefore, various neurobehavioral problems of children of drug-dependent parents could be attributed to inadequate maternal behavior or prenatal exposure to drugs. Thus, the aim of this research was to analyze the effects of chronic cocaine administration during pregnancy on postpartum maternal behavior. To do this, 21 CD1 pregnant female mice were randomly assigned for administration of saline solution and cocaine (25 mg/kg/day and 50 mg/kg/day), from day 8 to 21 of gestation. After delivery, for 15 minutes a day, during 20 days, the frequency of occurrence of 16 behavioral patterns of maternal behavior was individually recorded, using an ethogram. Cocaine slightly affected maternal behavior frequency, although it may have affected other parameters, such as latency, duration, and sequence of this behavior.

Resumo O abuso materno de cocaína durante a gestação está relacionado com negligência, maltrato, perturbação do vínculo mãe-filho, o que incide diretamente no desenvolvimento das crianças. Por isso, as diversas problemáticas neurocomportamentais dos filhos de pais drogodependentes poderiam ser atribuídas ao inadequado comportamento materno ou à exposição prénatal à droga. O objetivo desta pesquisa foi analisar os efeitos da administração crônica de cocaína durante a gestação no comportamento materno pós-parto de ratos. Para isso, designaram-se aleatoriamente 21 ratos CD1 fêmeas gestantes para a administração de solução salina e cocaína (25 mg/kg/dia e 50 mg/kg/dia), desde o oitavo até o 21° dia de gestação. Após o parto, durante 20 dias (15 minutos diários), registrou-se individualmente a frequência de apresentação de 16 índices de comportamento materno mediante um etograma. Constatou-se que a cocaína afetou levemente a frequência do comportamento materno, embora possivelmente afete outros parâmetros como latência, duração e sequência desse comportamento.

Resumen El abuso materno de cocaína durante la gestación se relaciona con negligencia, maltrato y perturbación del vínculo madre-hijo, lo que incide directamente en el desarrollo de los infantes; por esto, las diversas problemáticas neuroconductuales de los hijos de padres drogodependientes podrían atribuirse a la inadecuada conducta materna o a la exposición prenatal a la droga. El objetivo de esta investigación fue analizar los efectos de la administración crónica de cocaína durante la gestación en la conducta materna postparto de ratones. Para esto se asignaron aleatoriamente 21 ratones CD1 hembras gestantes para la administración de solución salina y cocaína (25 mg/kg/día y 50 mg/kg/día), desde el octavo hasta el día veintiuno de gestación. Después del parto, durante 20 días (15 minutos diarios), se registró individualmente la frecuencia de presentación de 16 índices de conducta materna mediante un etograma. Se encontró que la cocaína afectó levemente la frecuencia de la conducta materna, aunque posiblemente afecte otros parámetros como la latencia, duración y secuencia de esta conducta.

Perception and consumption of alcohol among the immigrant population from Latin America in Valencia region (Spain).

This study examines patterns of alcohol consumption among the Hispanic immigrant population in Valencia (Spain), and also whether the length of immigrants' residence in our country and perceived degree of discrimination have any influence on such patterns. A total of 610 Spanish-speaking immigrants (314 women, 296 men) over 15 years of age, from six Hispano-American countries were interviewed in 2006; 76.8% had consumed alcohol in the previous 12 months; 37.6% drink more alcohol in Spain than in their country of origin. This study shows the need to develop specific programs for the immigrant population, with special consideration for the young, males, and smokers. The study's limitations are noted.

Diffuse reflectance spectroscopy characterization of hemoglobin and intralipid solutions: in vitro measurements with continuous variation of absorption and scattering.

Absorption and scattering processes in biological tissues are studied through reflectance spectroscopy in tissue-like phantoms. For this aim, an experimental setup is designed to independently control both processes in hemoglobin and intralipid solutions. From the analysis of the obtained spectra, a simple empirical power law equation is found that relates absorbance with scattering and absorption coefficients. This relationship includes three wavelength independent parameters, which can be determined geometry from in vitro measurements for each particular optical optode. The dependence of the optical path length on the absorption and scattering coefficients is also analyzed, and estimations of this parameter for physiological conditions are presented. This study is useful to better understand the scattering phenomena in biological tissue, and to obtain absolute concentration of absorber particles when a homogeneous medium can be assumed.

Toxicological and pharmacological effects of D-arginine.

D-Arginine is extensively used in studies on L-arginine/nitric oxide pathway as an inactive form of L-arginine, even in man. In addition, it has previously been reported that this D-amino acid appears to have pharmacological activity. The present work aimed at evaluating the toxicity and pharmacology of D-arginine administered by the intraperitoneally route in albino male mice. Toxicity of D-arginine, alone as well as in the presence of propranolol and betamethasone was evaluated. D-Arginine in mice showed a light toxicity order (DL50: 2800 mg/kg). Previous injection of the beta-adrenoceptor blocker, propranolol (2 mg/kg, intraperitoneally), or betamethasone (0.5 mg/kg, intraperitoneally) produced a decrease in the toxicity of D-arginine (LD50: 3600 mg/kg, 3300 mg/kg, respectively). Also, a neuropharmacological screening of D-arginine using behavioural, neurological, autonomic, barbiturate-induced sleep time and pentylenetetrazole-induced convulsions tests were performed. D-Arginine 700 mg/kg displayed central stimulant properties, whereas a depressant profile was observed at a dose of 1400 mg/kg. In addition, D-arginine 1400 mg/kg produced a potentiation of pentobarbital sleeping time and a marked anticonvulsivant action against pentylenetetrazole.

Simultaneous monitoring of nitric oxide, oxyhemoglobin and deoxyhemoglobin from small areas of the rat brain by in vivo visible spectroscopy and a least-square approach.

Nitric oxide (NO) is a versatile molecule involved in a wide range of biological processes. Under physiological conditions, NO reacts with oxyhemoglobin (OxyHb) to form methemoglobin (MetHb) at a very high rate. Previous works have shown that MetHb is proportional to NO and that MetHb absorption contributes to the in vivo absorption spectrum recorded with visible spectroscopy using optical fibers. However, in vivo spectrophotometric monitoring of a single molecule has long been a problem because the overlapping of OxyHb, deoxyhemoglobin (DeoxyHb), MetHb, cytochromes and other chromophores absorption spectra make in vivo quantitative spectroscopy difficult. The aim of this work was to evaluate the possibility of obtaining the contribution of each main endogenous chromophore, especially OxyHb, DeoxyHb and MetHb, to the in vivo visible absorption spectrum recorded from rat cortex, hippocampus and striatum. A least-square approach with a fitting equation containing the in vitro spectrum of the main endogenenous chromophores was used. The validity of this approach was studied by increasing the endogenous MetHb level with NO infusion and by biliverdin perfusion. Data indicate that in vivo visible spectroscopy in combination with the least-square fitting method may be a useful tool for gaining insight into the roles of NO, hemoglobins and the interaction between them even from small cerebral areas.

Add-on gabapentin in the treatment of opiate withdrawal.

Gabapentin is an antiepileptic drug shown to be effective in the treatment of pain disorders and appears to be useful as well for several psychiatric disorders, including bipolar disorder, anxiety disorders, alcohol withdrawal and cocaine dependence. Gabapentin, at a dose of 600 mg three times a day, was evaluated as an add-on medication to a standard detoxification regime in seven heroin dependent individuals undergoing outpatient opiate withdrawal treatment. All seven patients successfully completed opiate detoxification and commenced opiate antagonist treatment with naltrexone on day five of withdrawal treatment, as scheduled. No adverse event was noted. Gabapentin appeared to lead a reduction in symptomatic medication and an overall beneficial effect on symptoms of heroin withdrawal.

In vivo spectroscopy: a novel approach for simultaneously estimating nitric oxide and hemodynamic parameters in the rat brain.

Nitric oxide (NO) is a versatile molecule involved in a wide range of biological processes. Under physiological conditions, NO reacts with oxyhemoglobin (OxyHb) to form methemoglobin (MetHb) at a very high rate. Microdialysis studies have used hemoglobin solutions as a trapping method to quantify NO in vivo. The methodology described here uses the microcapillary network with endogenous OxyHb instead of microdialysis probe with exogenous OxyHb for monitoring MetHb as an indirect index of NO levels by in vivo spectroscopy using optical fibers. This new method has been validated in rat cerebral cortex by the infusion of NO or well-known drug-induced changes in NO concentration (NMDA agonists and a NO-synthase inhibitor) and by comparing results with simultaneous voltammetric recordings. Results indicate that this spectroscopy technique is able to record large increases in MetHb levels and to detect reductions of its basal levels. In addition, data show that similar changes and kinetics can be observed with both techniques. Thus, intravascular MetHb can be used as an indirect index of NO levels. It is proposed that in vivo spectroscopy may be a useful tool to gain insight into the roles of NO in hemodynamic parameters and in other physiological processes such as the regulation of the mitochondrial respiratory chain.