[Analysis of the demand for detection of SARSCoV-2 in a health area of Spain]. / Análisis de la demanda de detección de SARS-CoV-2 en un área de salud de España.

OBJECTIVE: Since the discovery of the SARS-CoV-2 virus, the polymerase chain reaction technique (RT-PCR) has become the fundamental method for diagnosing the disease in its acute phase. The objective is to describe the demand-based series of RT-PCR determinations received at a Microbiology Service at a third-level reference hospital for a health area for three months spanning from the onset of the epidemic by SARS-CoV-2. METHODS: A retrospective analysis of the total of the RT-PCR requested in the Microbiology Service analyzed from 02/25/2020 to 05/26/2020 (90 days) has been carried out. They have been grouped by epidemiological weeks and by the petitioner service. A descriptive analysis was carried out by age, gender and number of requests for each patient. In the tests carried out, a confidence level of 95% (p <0.05) was considered significant. RESULTS: A total of 27,106 requests was received corresponding to 22,037 patients. Median age 53.7 (RIC 40.9-71.7) years, women: 61.3%. Proportion of patients with any positive RT-PCR: 14%. Of the total requests for RT-PCR, positive 3,710. Week 13 had the highest diagnosis performance (39.0%). The primary care has been the service thar has made the most requests (15,953). Patients with 3 or more RT-PCR: 565, of them, 19 patients had a positive result after previously having a negative one. CONCLUSIONS: Requests have been increasing depending on the evolution of the epidemic. The RT-PCR has a high diagnostic performance in the phases of highest contagiousness and / or transmissibility of the virus.

Post-mortem microbiology in sudden death: sampling protocols proposed in different clinical settings.

BACKGROUND: Autopsies, including minimally invasive autopsies, are a powerful tool for determination of the cause of death. When a patient dies from an infection, microbiology is crucial to identify the causative organism. Post-mortem microbiology (PMM) aims to detect unexpected infections causing sudden deaths; confirm clinically suspected but unproven infection; evaluate the efficacy of antimicrobial therapy; identify emergent pathogens; and recognize medical errors. Additionally, the analysis of the thanatomicrobiome may help to estimate the post-mortem interval. AIMS: The aim was to provide advice in the collection of PMM samples and to propose sampling guidelines for microbiologists advising autopsy pathologists facing different sudden death scenarios. SOURCES: A multidisciplinary team with experts in various fields of microbiology and autopsies on behalf of the ESGFOR (ESCMID - European Society of Clinical Microbiology and Infectious Diseases - study group of forensic and post-mortem microbiology and in collaboration with the European Society of Pathology) developed this narrative review based on a literature search using MedLine and Scopus electronic databases supplemented with their own expertise. CONTENT: These guidelines address measures to prevent sample contamination in autopsy microbiology; general PMM sampling technique; protocols for PMM sampling in different scenarios and using minimally invasive autopsy; and potential use of the evolving post-mortem microbiome to estimate the post-mortem interval. IMPLICATIONS: Adequate sampling is paramount to identify the causative organism. Meaningful interpretation of PMM results requires careful evaluation in the context of clinical history, macroscopic and histological findings. Networking and closer collaboration among microbiologists and autopsy pathologists is vital to maximize the yield of PMM.

Risk models for patients with localised renal cell carcinoma. / Modelos de riesgo en pacientes con carcinoma de células renales localizado.

INTRODUCTION: We conducted a retrospective analysis of our series to assess the factors that influenced disease-free survival (DFS) and cancer-specific survival (CSS) for patients with localised renal cell carcinoma (RCC). We also created our own risk groups. MATERIAL AND METHODS: Between January 1990 and December 2012, 596 patients underwent surgery for localised RCC (clear cell, papillary or chromophobe). Using Cox regression models, we analysed the clinical-pathological variables that influenced DFS and CSS and designed risk groups for DFS and CSS with the variables. RESULTS: The median follow-up for the series was 5.96 years. By the end of the study, 112 patients (18.8%) had a recurrence of the disease, with DFS rates of 82%, 77% and 72% at 5, 10 and 15 years, respectively. The independent factors that influenced DFS in the multivariate study were the following: A Furhman grade of 3-4, haematuria, lymphocytic or vascular invasion, the presence of tumour necrosis and a disease stage pT3-pT4. Furthermore, by the end of the study, 57 patients (9.6%) died due to renal cancer, with CSS rates of 92%, 86% and 83% at 5, 10 and 15 years, respectively. The independent factors that influenced CSS in the multivariate study were the following: A Furhman grade of 3-4, perinephric fat invasion and the presence of tumour necrosis. CONCLUSIONS: Factors in addition to the disease stage pT3-pT4 in patients with localised RCC are important, such as the presence of haematuria and lymphocytic or vascular invasion for DFS. A Furhman grade of 3-4 and the presence of tumour necrosis are especially relevant for DFS and CSS.

Predicting the effectiveness of extracorporeal shock wave lithotripsy on urinary tract stones. Risk groups for accurate retreatment. / Predicción de efectividad de litotricia extracorpórea por ondas de choque en cálculos del tracto urinario. Grupos de riesgo para precisar retratamiento.

INTRODUCTION: Extracorporeal shock wave lithotripsy (ESWL) is a non-invasive, safe and effective treatment for urinary tract lithiasis. Its effectiveness varies depending on the location and size of the stones as well as other factors; several sessions are occasionally required. The objective is to attempt to predict its success or failure, when the influential variables are known beforehand. MATERIAL AND METHODS: We analysed 211 patients who had had previous CT scans and were treated with ESWL between 2010 and 2014. The influential variables in requiring retreatment were studied using binary logistic regression models (univariate and multivariate analysis): maximum density, maximum diameter, area, location, disintegration and distance from the adipose panniculus. With the influential variables, a risk model was designed by assessing all possible combinations with logistic regression (version 20.0 IBM SPSS). RESULTS: The independent influential variables on the need for retreatment are: maximum density >864HU, maximum diameter >7.5mm and pyelocaliceal location. Using these variables, the best model includes 3risk groups with a probability of requiring significantly different retreatment: group 1-low risk (0 variables) with 20.2%; group 2-intermediate risk (1-2 variables) with 49.2%; and group 3-high risk (3 variables) with 62.5%. CONCLUSIONS: The density, maximum diameter and pyelocaliceal location of the stones are determinant factors in terms of the effectiveness of treatment with ESWL. Using these variables, which can be obtained in advance of deciding on a treatment, the designed risk model provides a precise approach in choosing the most appropriate treatment for each particular case.

Spanish experience on the design of radon surveys based on the use of geogenic information.

One of the requirements of the recently approved EU-BSS (European Basic Safety Standards Directive, EURATOM, 2013) is the design and implementation of national radon action plans in the member states (Annex XVIII). Such plans require radon surveys. The analysis of indoor radon data is supported by the existing knowledge about geogenic radiation. With this aim, we used the terrestrial gamma dose rate data from the MARNA project. In addition, we considered other criterion regarding the surface of Spain, population, permeability of rocks, uranium and radium contain in soils because currently no data are available related to soil radon gas concentration and permeability in Spain. Given that, a Spanish radon map was produced which will be part of the European Indoor Radon Map and a component of the European Atlas of Natural Radiation. The map indicates geographical areas with high probability of finding high indoor radon concentrations. This information will support legislation regarding prevention of radon entry both in dwellings and workplaces. In addition, the map will serve as a tool for the development of strategies at all levels: individual dwellings, local, regional and national administration.

Prognostic value of seminal vesicle involvement due to prostate cancer in radical prostatectomy specimens.

OBJECTIVE: To study the influence, in terms of prognosis, of the finding of seminal vesicle involvement in patients with prostate adenocarcinoma treated with radical prostatectomy. MATERIAL AND METHOD: We reviewed a series of patients with seminal vesicle involvement with clinically localized prostate adenocarcinoma who underwent radical prostatectomy between 1989 and 2009, focusing on their clinical-pathological characteristics, biochemical progression-free survival (BPFS) and specific survival (SS). We assessed the variables that influenced BPFS and designed a risk model. RESULTS: A total of 127 out of 1,132 patients who underwent surgery (11%) presented seminal vesicle invasion (i.e., pT3b). In the multivariate study of the entire series (Cox model), pT3b affects the BPFS (HR: 2; 95% CI: 1.4-3.3; P=.001). Other influential factors were the affected borders, initial prostate-specific antigen levels, pathological Gleason score and the presence of palpated tumor. The pT3b tumors have poorer clinical-pathological variables when compared with pT2 and pT3a tumors. Sixty-five percent of the patients evidenced biochemical progression. The BPFS was significantly poorer for pT3b (40 ± 4% and 28 ± 4% at 5 and 10 years, respectively) than for pT2 and pT3a (P<.0001). The SS was also poorer in patients with pT3b tumors (91 ± 2% and 76 ± 4% at 5 and 10 years, respectively) (P<.0001). The predictors within the pT3b patient group were: PSA levels >10 ng/mL (HR: 1.9; 95% CI: 1.04-3.6; P=.04) and pathological Gleason score 8-10 (HR: 2.1; 95% CI: 1.2-3.5; P=.03). We designed a risk model that accounts for the variables involved, which entails 2 groups with different BPFS (P=.004): Group 1 (0-1 variable), with a BPFS of 46 ± 7% and 27 ± 8% at 5 and 10 years, respectively; and Group 2 (2 variables), with a BPFS of 14 ± 7% and 5 ± 5% at 5 and 10 years, respectively. CONCLUSION: Seminal vesicle involvement severely and negatively affects the BPFS and SS. We designed a risk model with the independent influential variables in BPFS (pathological Gleason score 8-10 and PSA levels >10 ng/mL). This model confirms that pT3b tumors are a heterogeneous group, which includes an important group with better prognosis when surgical treatment is performed.

The Spanish indoor radon mapping strategy.

Indoor radon mapping still represents a valuable tool for drawing the picture of the exposure of general public due to radon and radon progeny inhalation in a residential context. The information provided by means of a map is useful not only as awareness and strategic element for authorities and policy-makers, but also as a scientific start-up point in the design of epidemiological and other specific studies on exposure to natural radiation. The requirements for a good mapping are related to harmonisation criteria coming from European recommendations, as well as to national/local characteristics and necessities. Around 12,000 indoor radon measurements have been made since the Spanish national radon programme began at the end of the 1980s. A significant proportion of them resulted from the last campaign performed from 2009 to 12. This campaign completed the first version of a map based on a grid 10 × 10 km(2). In this paper, the authors present the main results of a new map together with the criteria adopted to improve the number of measurements and the statistical significance of them.

Simulators help improve student confidence to acquire skills in urology.

OBJECTIVE: To know the level of confidence of fifth year medical students in order to perform maneuvers in bladder catheterization and rectal examination before and after training with simulators. To be able to assess student satisfaction regarding the use of the simulation as a learning method. MATERIAL AND METHODS: The study was conducted in the Simulation Center of the Faculty of Medicine. A total of 173 students who completed a practical workshop on the subject of Urology participated. The students were asked to answer anonymous questionnaires on their level of confidence in performing a bladder catheterization and rectal examination before and after the workshop as well as their satisfaction in using the simulation as a training tool. The workshops were organized using groups of 10 students. A teacher or a resident in that area of expertise supervised each student individually, resolving their doubts and teaching them the proper technique. RESULTS: All the evaluations made on the different abilities were significantly higher after training (P<.001). Significant differences were found in the confidence level between men and women before the training regarding male urethral catheterization maneuvers and recognition of normal or pathological prostate, The confidence level was lower in women (P<.05). These differences disappeared after training. The level of overall satisfaction with the workshop was high, going from 4.47 ± 0.9 to a maximum score of 5. CONCLUSIONS: Simulation is a training method that helps improve the confidence of the medical student in performing a bladder catheterization and digital rectal examination.

[Malignant priapism: conservative management of a case]. / Priapismo maligno: un caso manejado de forma conservadora.

Priapism is an urological emergency which requires investigation, especially to differentiate between ischemic and non-ischemic priapism. Initial management is carried out through aspiration and gasometry of blood from the corpus cavernosum. We report the case of a 69-year-old patient with urothelium carcinoma of the bladder T2 G3 and metastasis in urethra/corpus cavernosum who requested an emergency consultation because of edema and a penile erection lasting several days. Due to the poor prognosis and the imaging test, a conservative management was carried out.

Intercomparison exercise on external gamma dose rate under field conditions at the laboratory of natural radiation (Saelices el Chico, Spain).

The last nuclear accident in Fukushima nuclear power plant has increased the necessity for measuring radiation in the environment. Therefore, radiation monitors providing results traceable throughout the country become essential and it is very important to test them under the same environmental conditions. The first intercomparison of natural radioactivity under field conditions was held in Saelices el Chico (Salamanca, Spain) in May 2011, including an exercise on environmental dose rate. This article presents the results achieved by 19 instruments belonging to 12 institutions from 7 different countries. The tested detectors are proportional counters, ionisation chambers, Geiger-Müller and scintillators measuring dose rate in three stations with reference values from 110 to 1800 nGy h(-1). All the results were given in terms of air kerma (nGy h(-1)) and the measurements show agreement within 25 % in all the sites. Evaluation criteria based on accuracy and statistical uncertainty were also carried out and 25 % of participants passed the test in all sites.

Function and expression of renal epithelial sodium transporters in rats with thyroid dysfunction.

Thyroid disorders are accompanied by major changes in renal sodium handling and blood pressure. Sodium transporters play a crucial role in regulating sodium excretion. We determined the function and expression of type 3 Na/H (NHE3) exchanger, type 2 Na+K+2Cl co-transporter (NKCC2) co-transporter, NaCl co-transporter (NCC) cotransporter, and epithelial sodium channel (ENaC) in hypoand hyperthyroid rats at 6 weeks after each thyroid disorder induction. We measured the renal response to functional blockade of the tubular sodium transporters, using acetazolamide to inhibit the activity of NHE3, furosemide for NKCC2, hydrochlorotiazide for NCC, and amiloride for ENaC. Expression of sodium transporters was analyzed by measuring the protein abundance by Western blot. The responsiveness to NHE3 inhibition and NHE3 protein was lower in hypothyroid rats and higher in hyperthyroid rats vs controls. Hypothyroid rats showed greater diuretic and natriuretic responses to NKCC2 and ENaC blockade and higher protein abundance of NKCC2 vs controls. Hyperthyroid rats showed greater protein expression of NKCC2 and NCC vs controls. Groups did not differ in responsiveness to NCC blockade. The expression and activity of ENaC were lower in hyperthyroid rats. In conclusion, reduced NHE3 activity may participate in the low blood pressure of hypothyroid rats and elevated NHE3 activity in the high blood pressure of hyperthyroid rats. These proximal alterations are counter-balanced by functional upregulation of NKCC2 and ENaC in downstream nephron segments of hypothyroid rats and by downregulation of αENaC activity and expression in hyperthyroid rats.

Effectiveness and safety of tranexamic acid administration during total knee arthroplasty.

BACKGROUND: The administration of tranexamic acid (TA) is associated with a decrease in the number of red blood cell (RBC) units transfused. However, concerns about its safety have hindered its broader use. STUDY DESIGN AND METHODS: We evaluated the effect of TA on RBC transfusion and thromboembolic complications in total knee arthroplasty. We retrospectively studied 414 patients, 215 immediately before introducing TA treatment (control group) and after, in 199 patients without history of thromboembolic diseases (TA group). In a subgroup of patients, a lower extremities contrast venography was performed. RESULTS: Fifty-four per cent of control group patients were transfused with RBC while only 17.6% of TA group patients received RBCs. In the TA that group, those transfused received less units (2.83 vs. 1.89), showed smaller mean calculated perioperative blood loss and haemoglobin values at discharge were higher compared to control group (10.1 vs. 9.3 g/dl). Thromboembolic complications were diagnosed in 2.8% of the patients in the control group and in 1.5% in the TA group. Asymptomatic distal deep venous thrombosis was found in 54 (14.8%) of TA group patients and 54 (30.1%) of control patients. TA administration reduced the expenditure for RBC transfusion plus the cost of TA from 148.94 to 33.87 euro per patient. CONCLUSION: Routine administration of TA during total knee arthroplasty to patients without history of thromboembolic disease is associated with a 67% reduction in RBC transfusions and, in those transfused, with a reduction in the number of units administered. TA treatment was not associated with an increase in thromboembolic complications. Transfusion costs are significantly reduced.

New antiherpetic 1,3-phenylene derivatives, inhibitors of the interaction of the HSV-1 origin binding protein (OBP) with DNA.

The synthesis of new 1,3-phenylene derivatives and their preliminary evaluation as antivirals (Herpes simplex 1, HSV-1) whose antiherpetic activity can be related with the inhibition of the interaction of the origin binding protein (OBP) with the DNA are presented. The new compounds are adjusted to a previously defined common structural model, consisting of a central aromatic system, which presents two side chains of different lengths in relative position 1, 3; these chains are made up of atomic groups characterized by the alternation of positive and negative centers, situating differently substituted rings, preferably aromatic, at the ends of both chains. Some of these derivatives, such as N,N''-(4-methoxy-1,3-phenylene)bis[N'-(4-nitrophenyl)urea] (2c) or (1,3-phenylene)bis[N-(p-tolyl)aminosulfonyl] (11b), show antiherpetic activity related to the proposed mechanism.

Allopurinol encapsulated in polycyanoacrylate nanoparticles as potential lysosomatropic carrier: preparation and trypanocidal activity.

The activity of allopurinol-loaded polyethylcyanoacrylate nanoparticles against Trypanosoma cruzi was compared to that of free allopurinol using in vitro cultures of epimastigotes. Ethylcyanoacrylate nanoparticles were prepared by an emulsion polymerization process, and formulations containing different concentrations of allopurinol, polyethylcyanoacrylate and surfactants were investigated and analyzed in size and amount of drug entrapped. The nanoparticles obtained were less than 200 nm in size, as measured by electron microscopy and cytometry. The peak amount of allopurinol entrapped in the nanoparticles was 62.8+/-1.9 microg mg(-1) of nanoparticles using 400 microl of polyethylcyanoacrylate, 200 microl of surfactant (Tween 20) and 20 mg of allopurinol in 50 ml of polymerization medium and the association efficiency was 100.7%. After 6 h of incubation at pH 7.4 the release of allopurinol from the nanoparticles was 7.4%, while at pH 1.2 only 3.1% was released after 4-6 h (t=42.8, P<0.0001). The in vitro studies, using cultures of T. cruzi epimastigotes, demonstrated considerable increases in the trypanocidal activity of the allopurinol-loaded nanoparticles in comparison with a standard solution of allopurinol (91.5 vs. 45.9%) at an allopurinol concentration of 16.7 microg ml(-1). In addition, it was shown that the unloaded nanoparticles, by mechanisms not completely elucidated, had a trypanocidal activity similar to that of standard solutions of allopurinol. To study cytotoxicity, increasing concentrations of unloaded nanoparticles were incubated on vero-line cell cultures. The concentration that killed 50% cells was 200 microg ml(-1), four times higher than that necessary to kill 50% of T. cruzi. It is concluded that the polyethylcyanoacrylate nanoparticles constitute a good carrier of drugs against the T. cruzi. The allopurinol loaded-nanoparticles significantly increased the trypanocidal activity in comparison to the free drug.

Synthesis and anti-HIV-1 activities of new pyrimido[5,4-b]indoles.

A set of new pyrimido[5,4-b]indole derivatives that are structurally related to some non-nucleside HIV-1 reverse transcriptase inhibitors were synthesized and biologically evaluated for their activity as inhibitors of wild and mutant HIV-1 RT types in an 'in vitro' recombinant HIV-1 RT screening assay, as well as anti-infectives in HLT4lacZ-1IIIB cells. Preliminary structure-activity relationships suggest that activity is promoted by simultaneous substitution in positions 2 and 4, especially when chains of alkyldiamine type are present, and by electron-releasing substituents (methoxy) in positions 7 and 8. The inactivity or the very low activity of title derivatives does not suggest interest in AIDS therapy.

Characterization and trypanocidal activity of nifurtimox-containing and empty nanoparticles of polyethylcyanoacrylates.

The aim of this study was to evaluate the utility of nanoparticles of polyalkylcyanoacrylate as a targeted delivery system for nifurtimox against Trypanosoma cruzi, responsible for Chagas' disease. Ethylcyanoacrylate nanoparticles were prepared by an emulsion polymerization process and formulations containing different concentrations of nifurtimox, polyethylcyanoacrylates and surfactants were investigated and analysed for size and drug content. The nanoparticles obtained were less than 200 nm in size, as measured by electron microscopy and cytometry. The peak percentage of nifurtimox uptake into the nanoparticles was 33.4% for use of 500 microL polyethylcyanoacrylate, 200 microL surfactant (Tween 20) and 10 mg nifurtimox in 50 mL polymerization medium. The highest release of nifurtimox from the nanoparticles was 65.4% after 6-h incubation at pH 7.4. In-vitro studies using cultures of T. cruzi epimastigotes revealed considerably increased trypanocidal activity compared with a standard solution of nifurtimox. Studies of cell cultures previously infected with metacyclic forms of the parasite showed that only 2-h treatment with solutions of 0.001% of the nanoparticle suspension reduced parasitism by 87-94% both when the nanoparticles were loaded with nifurtimox and when unloaded. Electron-microscopic examination revealed processes of degeneration and lysis, suggesting apoptotic processes, in intracellular amastigotes and free amastigotes treated with the nanoparticles. It was demonstrated that unloaded nanoparticles, by mechanisms not completely elucidated, have trypanocide activity similar to that of a standard solution of nifurtimox. It is concluded that the nanoparticles loaded with nifurtimox constitutes a good carrier of the drug against T. cruzi. The loaded-nanoparticles significantly increase trypanocidal activity.