Endodontic variables in patients with SARS-CoV-2 infection (COVID-19) in relation to the severity of the disease.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) is the cause of the ongoing coronavirus disease 2019 (COVID-19) pandemic. It has been hypothesized oral health may be related to the severity and complications of COVID-19. The aim of this study was to analyze the prevalence of apical periodontitis and the frequency of root canal treatment in a sample of patients with SARS-CoV-2 infection (COVID-19), correlating them with the severity of the disease. MATERIAL AND METHODS: This retrospective study was conducted following the Strengthening Reporting Observational Studies in Epidemiology (STROBE) guidelines. The study examined 280 patients with positive real time PCR COVID-19 test whose treatment was performed in our hospital. Fifty-two patients aged 52.3 ± 17.3 years, including 30 males and 22 females, who had an orthopantomography in their clinical record, performed in the last 2 years, were included. Patients with SARS-CoV-2 infection were grouped as mild or moderate (MM) and severe or critical (SC) illness groups, according to the NIH COVID-19 Treatment Guidelines (Wu & McGoogan 2020). Radiographic records were analyzed and apical periodontitis (AP) was diagnosed as radiolucent periapical lesions (RPLs), using the periapical index score (PAI). Student's t test, χ2 test and multivariate logistic regression were used in the statistical analysis. RESULTS: The number of carious teeth was significantly higher in the SC group (3.4 ± 4.1), which showed more than twice as many teeth with carious lesions than the MM group (1.4 ± 1.8) (p = 0.02). Multivariate regression analysis showed association between the number of carious teeth and the severity of SARS-CoV-2 disease (OR = 1.5; 95% CI = 1.1-2.1; p = 0.017). Endodontic status (OR = 7.12; 95% CI = 1.2-40.9; p = 0.027) also correlated with the disease severity. CONCLUSIONS: The results suggest that the oral health status of COVID-19 patients correlated with the severity of the SARS-CoV-2 virus infection. Significant association has been found between the severity of COVID-19 disease and the presence of a greater number of teeth with caries lesions, as well as with endodontic status.

Immunohistochemical analysis of T-type calcium channels in acquired melanocytic naevi and melanoma.

BACKGROUND: Cutaneous malignant melanoma arises from transformed melanocytes de novo or from congenital or acquired melanocytic naevi. We have recently reported that T-type Ca2+ channels (TT-Cs) are upregulated in human melanoma and play an important role in cell proliferation. OBJECTIVES: To describe for the first time in formalin-fixed paraffin-embedded tissue the immunoexpression of TT-Cs in biopsies of normal skin, acquired melanocytic naevi and melanoma, in order to evaluate their role in melanomagenesis and/or tumour progression, their utility as prognostic markers and their possible use in targeted therapies. METHODS: Tissue samples from normal skin, melanocytic naevi and melanoma were subjected to immunohistochemistry for two TT-Cs (Cav3.1, Cav3.2); markers of proliferation (Ki67), the cell cycle (cyclin D1), hypoxia (Glut1), vascularization (CD31) and autophagy (LC3); BRAF V600E mutation (VE1) and phosphatase and tensin homologue (PTEN). Immunostaining was evaluated by histoscore. In silico analysis was used to assess the prognostic value of TT-C overexpression. RESULTS: TT-C immunoexpression increased gradually from normal skin to common naevi, dysplastic naevi and melanoma samples, but with differences in the distribution of both isoforms. Particularly, Cav3.2 expression was significantly higher in metastatic melanoma than in primary melanoma. Statistical correlation showed a linear interaction between PTEN loss/BRAF V600E/Cav3.1/LC3/ Ki67/cyclin D1/Cav3.2/Glut1. Disease-free survival (DFS) and overall survival correlated inversely with overexpression of Cav3.2. DFS also correlated inversely with overexpression of Cav3.1. CONCLUSIONS: TT-C immunoexpression on melanocytic neoplasms is consistent with our previous in vitro studies and appears to be related to tumour progression. TT-C upregulation can be considered as a prognostic marker using The Cancer Genome Atlas database. The high expression of Cav3.2 in metastatic melanoma encourages the investigation of the use of TT-C blockers in targeted therapies.

Epidemiological profile of smoking and nicotine addiction among asthmatic adolescents.

OBJECTIVE: Despite the harmful effects of cigarette smoking, this habit in asthmatic adolescents continues to be a health problem worldwide. Our objectives were to determine the epidemiological profile of smoking and the degree of nicotine dependence among asthmatic adolescents. STUDY DESIGN: Through a cross-sectional investigation, 3383 adolescents (13-19 years of age) were studied. METHODS: Information was collected using a previously validated questionnaire. Two study groups of adolescent smokers were formed: one composed of asthmatic adolescents and the other of healthy youths. RESULTS: Asthmatic adolescents were found to be more likely to smoke (21.6% vs 11.8%) and to have some degree of nicotine dependence compared with healthy adolescents (51.6% vs 48.8%). The most important characteristic of smoking in asthmatic adolescents was found to be an onset before 11 years of age due to curiosity about cigarettes. Asthmatic youths continue smoking because this habit decreases their anxiety and stress. Adolescents know that smoking is addictive and often smoke on waking up in the morning or when they are sick. Yet, these adolescents do not consider smoking to be a problem. CONCLUSION: In this study, curiosity about cigarettes was the primary reason why asthmatic adolescents smoked for the first time and developed a greater dependence to nicotine compared with healthy adolescents. Moreover, the findings show that many of the factors that favour the development of smoking are preventable, given that they are present in the family and social environment.

Reduction of low temperature engine pollutants by understanding the exhaust species interactions in a diesel oxidation catalyst.

The interactions between exhaust gas species and their effect (promotion or inhibition) on the light-off and activity of a diesel oxidation catalyst (DOC) for the removal of pollutants are studied, using actual engine exhaust gases from the combustion of diesel, alternative fuels (rapeseed methyl ester and gas-to-liquid fuel) and diesel/propane dual fuel combustion. The activity of the catalyst was recorded during a heating temperature ramp where carbon monoxide (CO) and hydrocarbon (HC) light-off curves were obtained. From the catalyst activity tests, it was found that the presence of species including CO, medium-heavy HC, alkenes, alkanes, and NOx and their concentration influence the catalyst ability to reduce CO and total HC emissions before release to the atmosphere. CO could inhibit itself and other species oxidation (e.g., light and medium-heavy hydrocarbons) while suffering from competitive adsorption with NO. Hydrocarbon species were also found to inhibit their own oxidation as well as CO through adsorption competition. On the other hand, NO2 was found to promote low temperature HC oxidation through its partial reduction, forming NO. The understanding of these exhaust species interactions within the DOC could aid the design of an efficient aftertreatment system for the removal of diesel exhaust pollutants.

Finding synergies in fuels properties for the design of renewable fuels--hydroxylated biodiesel effects on butanol-diesel blends.

This article describes the effects of hydroxylated biodiesel (castor oil methyl ester - COME) on the properties, combustion, and emissions of butanol-diesel blends used within compression ignition engines. The study was conducted to investigate the influence of COME as a means of increasing the butanol concentration in a stable butanol-diesel blend. Tests were compared with baseline experiments using rapeseed methyl esters (RME). A clear benefit in terms of the trade-off between NOX and soot emissions with respect to ULSD and biodiesel-diesel blends with the same oxygen content was obtained from the combination of biodiesel and butanol, while there was no penalty in regulated gaseous carbonaceous emissions. From the comparison between the biodiesel fuels used in this work, COME improved some of the properties (for example lubricity, density and viscosity) of butanol-diesel blends with respect to RME. The existence of hydroxyl group in COME also reduced further soot emissions and decreased soot activation energy.

Health-related quality of life and mortality in the 'Seguimiento Universidad de Navarra' prospective cohort study.

OBJECTIVE: To study the association between health-related quality of life (HRQoL) and all-cause mortality in a healthy middle-aged Mediterranean cohort. METHODS: We included 15,390 participants -mean age 42.8 years at first HRQoL ascertainment, all university graduates-. HRQoL was assessed with the self-administered Medical Outcomes Study Short Form-36 (SF-36) twice, with a 4-year gap. We used multivariable-adjusted Cox regression models to address the relation between self-reported health and Physical or Mental Component Summary (PCS-36 or MCS-36) and mortality, and their interaction with prior comorbidities or adherence to the Mediterranean diet (MedDiet). RESULTS: Over 8.7 years of median follow-up time, 266 deaths were identified. Hazard ratio (HR) for the excellent vs. poor/fair category in self-reported health was 0.30 (95 % confidence interval (CI), 0.16-0.57) in the model with repeated measurements of HRQoL. Both the PCS-36 (HRquartile4(Q4)vs.Q1 0.57 [95%CI, 0.36-0.90], ptrend < 0.001; HRper+10points: 0.64 [95%CI, 0.54-0.75]) and the MCS-36 (HRQ4vs.Q1 0.67 [95%CI, 0.46-0.97], ptrend = 0.025; HRper+10points: 0.86 [95%CI, 0.74-0.99]) were inversely associated with mortality in the model with repeated measurements of HRQoL. Previous comorbidities or adherence to the MedDiet did not modify these associations. CONCLUSIONS: Self-reported HRQoL -assessed as self-reported health, PCS-36 and MCS-36- obtained with the Spanish version of the SF-36 were inversely associated with mortality risk, regardless of the presence of previous comorbidities or adherence to the MedDiet.

Time to positivity of blood culture association with clinical presentation, prognosis and ESBL-production in Escherichia coli bacteremia.

The time to positivity (TTP) of blood cultures has been associated with increased mortality in bacteremia caused by several microorganisms. The aim of this study is to evaluate the relationship between TTP and prognosis, clinical presentation and extended spectrum B-lactamase (ESBL)-production in patients with Escherichia coli bacteremia. This is a retrospective observational study involving 226 adult patients with E. coli bacteremia. Data collected included underlying diseases, clinical presentation, prognosis factors, TTP, ESBL-production and outcome. Thirty-one (14%) patients had severe sepsis and 29 (13%) septic shock at presentation. Thirty-three (14%) strains were ESBL-producers. Thirty-nine (17%) patients died during admission and 17 (7.5%) within 48 hours. The median TTP was 8.3 hours (range, 0.42­76.5). It was significantly shorter in patients with septic shock (6.23 h, range 1.12­47.29 h vs. 8.51 h, range 0.42­76.50 h; p = 0.018). Rapid growth of E. coli, Pitt index >1.5, non-urinary source and Charlson score >2 were selected as independent risk factors of in-hospital mortality by the multivariate analysis. ESBL-production was not associated with modifications in TTP. Lower TTP is an independent risk factor for septic shock and poor outcome in episodes of E. coli bacteremia. The TTP in E. coli bacteremia is not significantly modified by ESBL-production.

[Extracorporeal circulation in no-cardiac surgery: experience at the Clinica Universidad de Navarra]. / La circolazione extracorporea in chirurgia non cardiaca. Esperienza della Clinica Universitaria di Navarra.

AIM: Analyse the use of the Extra-Corporeal Circulation (ECC) in no-cardiac operations at the Clinica Universidad de Navarra. MATERIAL OF STUDY: Between 1985 and 2009, the ECC has been involved in 28 operations for retroperitoneal tumour with inferior vena cava thrombus, in 43 isolated hyperthermic perfusion of a limb for locally advanced cancer and in 8 cases of chest mass with invasion of the pulmonary veins or bronchial carina. RESULTS: The intraoperative mortality for renal cancer has been of 7% while the 28% of patients showed a major complication. None patient died for the isolated hyperthermic perfusion and the 81% showed no toxicity. 1 patient out of 8 for chest mass died during the surgery for impossibility of weaning from the ECC. DISCUSSION: The ECC has been utilised in our experience mostly in cases of advanced cancer. It is an aggressive technique with a certain rate of complications. Nevertheless mid- and long-term results are encouraging. CONCLUSION: The ECC is the only technique in some advanced cancer in order to safely perform the mass removal. The precise co-ordination of the team is necessary to reduce the complication rate.

Preemptive therapy for cytomegalovirus disease in allogeneic stem cell transplant recipients.

Cytomegalovirus (CMV) infection causes high morbidity and mortality among allogeneic stem cell transplant recipients. Preemptive therapy with oral valganciclovir or intravenous ganciclovir has replaced universal prophylaxis. We prospectively studied 19 consecutive adult recipients of allogeneic peripheral blood stem cell transplants from May 2005 through February 2007 to analyze the safety and efficacy of preemptive therapy for the treatment of CMV infection. The antigenemia test was persistently negative in 8 patients (42%) and positive at least once in 11 (58%). Eight patients were treated with oral valganciclovir on an outpatient basis and they all became CMV negative after the first week of treatment. The other 3 patients received intravenous ganciclovir and were also CMV negative after the first week of treatment. No patient abandoned treatment, no severe secondary toxicity was noted, and there was no CMV-associated mortality.

Review of the evidence on handling drugs and hazardous products in Urology Departments. Consensus document between the Spanish Urological Association and the Spanish Society of Hospital Pharmacy. / Revisión de la evidencia sobre el manejo de medicamentos y productos peligrosos en los servicios de Urología. Documento de consenso entre la Asociación Española de Urología y la Sociedad Española de Farmacia Hospitalaria.

BACKGROUND: The intravesical administration of hazardous drug products is a standard practice in the urology setting, which potentially exposing medical personnel to these drug products. It was deemed necessary to have a consensus document among the scientific societies involved (the Spanish Urological Association and the Spanish Society of Hospital Pharmacy) that collects the best available evidence on the safest handling possible of dangerous drug products in the setting of urology departments. METHODS: We reviewed the legislation and recommendations on the handling of dangerous drug products, both at the national and international level. RESULTS: There is national legislation and regulations for protecting workers who handle dangerous drugs and products, as well as recommendations for handling to protect both the product and workers. DISCUSSION: Following the strategic lines of the European Parliament for 2014-2020 in the chapter on occupational safety and health, the Spanish Urological Association and the Spanish Society of Hospital Pharmacy proposed a series of actions that decrease the risks of exposure for practitioners and caregivers involved in the handling of these products. CONCLUSIONS: After this review, 19 recommendations were established for handling dangerous drug products, which can be summarised as the need to train all individuals involved (from management teams to patients and caregivers), adopt systems that prevent contaminating leaks, implement exposure surveillance programmes and optimise available resources.

Administration of taurolidine-citrate lock solution for prevention of central venous catheter infection in adult neutropenic haematological patients: a randomised, double-blinded, placebo-controlled trial (TAURCAT).

BACKGROUND: Catheter-related bloodstream infection (CRBSI) is one of the most frequent complications in patients with cancer who have central venous catheters (CVCs) implanted and is associated with substantial morbidity and mortality. Taurolidine is a non-antibiotic agent with broad-spectrum antimicrobial activity, which has been used as a lock solution to prevent CRBSI in some settings. However, little is known about its usefulness in high-risk adult neutropenic patients with cancer. This prospective randomised clinical trial aims to test the hypothesis that taurolidine-citrate lock solution is more effective than placebo for preventing catheter infection in neutropenic haematological patients. METHODS: This study is a prospective, multicentre, randomised, double-blinded, parallel, superiority, placebo-controlled trial. Patients with haematological cancer who are expected to develop prolonged neutropenia (> 7 days) and who have a non-tunnelled CVC implanted will be randomised to receive prophylactic taurolidine-citrate-heparin solution using a lock technique (study group) or heparin alone (placebo group). The primary endpoint will be bacterial colonisation of the CVC hubs. The secondary endpoints will be the incidence of CRBSI, CVC removal, adverse events, and 30-day case-fatality rate. DISCUSSION: The lock technique is a preventive strategy that inhibits bacterial colonisation in the catheter hubs, which is the initial step of endoluminal catheter colonisation and the development of infection. Taurolidine is a nontoxic agent that does not develop antibiotic resistance because it acts as an antiseptic rather than an antibiotic. Taurolidine has shown controversial results in the few trials conducted in cancer patients. These studies have important limitations due to the lack of data on adult and/or high-risk neutropenic patients, the type of catheters studied (tunnelled or ports), and the lack of information regarding the intervention (e.g. dwelling of the solution, time, and periodicity of the lock technique). If our hypothesis is proven, the study could provide important solid evidence on the potential usefulness of this preventive procedure in a population at high risk of CRBSI, in whom this complication may significantly impair patient outcome. TRIAL REGISTRATION: ISRCTN, ISRCTN47102251 . Registered on 9 September 2015.

Two-dose daclizumab, tacrolimus, mycophenolate mofetil, and steroid-free regimen in de novo cardiac transplant recipients: early experience.

BACKGROUND: Tacrolimus (TAC) with mycophenolate mofetil (MMF) and a steroid-free regimen seems to have good efficacy in preventing acute rejection in cardiac transplant recipients, although concern exists about nephrotoxicity. Induction therapy with Daclizumab seems to give protection without side effects. Data are lacking about the outcome of 2-dose Daclizumab+TAC+MMF and a steroid-free regimen. MATERIALS AND METHODS: We retrospectively reviewed 28 consecutive de novo heart transplantations performed at a single center between January 2001 and June 2006. Patients received induction therapy with 2-dose Daclizumab. Maintenance immunosuppression included TAC, MMF, and prednisone during the first 6 months. The endpoints were the incidence of acute rejection, patient and graft survival, and clinical tolerability. RESULTS: Among 28 patients of mean age 57 +/- 9 years, 2 subjects (7%) died in the perioperative period due to infections. The mean follow-up was 2.8 +/- 1.5 years. There were no late deaths. Six patients experienced acute rejection (International Society of Heart and Lung Transplantation [ISHLT] >or=3A) that required treatment during the first 3 months. At follow-up, only 3 patients (>or=3A) required treatment. Mean creatinine level increased from 1.08 +/- 0.37 at baseline to 1.08 +/- 0.41 at 1 year (n = 23; P = not significant [NS]) to 1.39 +/- 0.68 (n = 13; P < .05) at 4 years, 1.65 +/- 0.51 (n = 8; P < .05) at 5 years. No patient required replacement therapy. CONCLUSIONS: A steroid-free protocol with 2-dose Daclizumab induction therapy and maintenance with TAC and MMF seemed to be safe to prevent acute rejection. Creatinine levels were slightly but significantly increased.

Impact on renal function of the use of sirolimus in cardiac transplantation.

INTRODUCTION: During the last few years sirolimus has been introduced as an alternative to preserve renal function in transplant recipients receiving calcineurin inhibitors. MATERIALS AND METHODS: We reviewed our results on the use of sirolimus in cardiac transplant recipients. RESULTS: Twenty-seven patients with an average age of 63 years received sirolimus. The average time after transplantation was 73.4 +/- 58.9 months and the average follow-up was 31.7 +/- 18.01 months. Sirolimus was prescribed in 37% of cases due to chronic renal failure (CRF), 14.8% because of cardiac allograft vasculopathy (CAV), 11.1% for tumors, 22.2% de novo, 7.4% for CRF and tumor, and 7.4% for CRF and CAV. Among the patients with CRF (n = 14), there were 5 (35%) on dialysis at the moment of starting the treatment and 1 was retired from dialysis. The other 4 (28.5%) patients had to be treated with dialysis after starting the treatment. In all, 42.8% of the patients with nephropathy maintained stable renal function or improved. Among the 17 (63%) patients who did not require dialysis, there was no significant change in renal function after 6 months or 1, 2, and 3 years follow-up. CONCLUSIONS: The use of sirolimus in cardiac transplantation maintains stable renal function in the majority of patients in the medium term.

Lipid rafts act as specialized domains for tetanus toxin binding and internalization into neurons.

Tetanus (TeNT) is a zinc protease that blocks neurotransmission by cleaving the synaptic protein vesicle-associated membrane protein/synaptobrevin. Although its intracellular catalytic activity is well established, the mechanism by which this neurotoxin interacts with the neuronal surface is not known. In this study, we characterize p15s, the first plasma membrane TeNT binding proteins and we show that they are glycosylphosphatidylinositol-anchored glycoproteins in nerve growth factor (NGF)-differentiated PC12 cells, spinal cord cells, and purified motor neurons. We identify p15 as neuronal Thy-1 in NGF-differentiated PC12 cells. Fluorescence lifetime imaging microscopy measurements confirm the close association of the binding domain of TeNT and Thy-1 at the plasma membrane. We find that TeNT is recruited to detergent-insoluble lipid microdomains on the surface of neuronal cells. Finally, we show that cholesterol depletion affects a raft subpool and blocks the internalization and intracellular activity of the toxin. Our results indicate that TeNT interacts with target cells by binding to lipid rafts and that cholesterol is required for TeNT internalization and/or trafficking in neurons.

[Cardiac and vascular homograft valves transplant]. / Trasplante de homoinjertos valvulares cardiacos y vasculares.

The advances in the manipulation of human tissues, the development of cryobiology, paediatric cardiac surgery, the impossibility of obtaining an ideal prosthetic cardiac valve and the surgical treatment of cardiovascular infections have revived interest in the use of homografts. The donors of these homografts can be: a) Live donors: aortic and pulmonary valve of the recipient of a heart transplant; b) Multiorgan donors with a diagnosis of death according to neurological criteria, whose heart is rejected for heart transplant; c) Cadaver donors with asystolia of less than 8 hours. Homograft cardiac valves are the substitute of choice in aortic valve endocarditis, patients with counter-indications for anticoagulation, reconstruction of the outflow tract of the right ventricle, aortic valve replacement in children and young adults through the Ross operation, and an optional indication is the aortic valve and/or rising aorta replacement in patients over 60 years of age. Although there are not sufficiently broad series of homogratfs with arterial substitutes, with respect to the number of patients and time of evolution, the results suggest that this can benefit patients with vascular infection, immunodepressed patients or complex patients whose technique during the operation might require a homograft.

[Heart transplant]. / Trasplante cardíaco.

A heart transplant is at present considered the treatment of choice in cases of terminal cardiac insufficiency refractory to medical or surgical treatment. Due to factors such as the greater life expectancy of the population and the more efficient management of acute coronary syndromes, there is an increasing number of people who suffer from heart failure. It is estimated that the prevalence of the disease in developed countries is around 1%; of this figure, some 10% are in an advanced stage and are thus potential receptors of a heart transplant. The problem is that it is still not possible to offer this therapeutic form to all of the patients that require it. Consequently, it is necessary to optimise the results of the heart transplant through the selection of patients, selection and management of donors, perioperative management and control of the disease due to graft rejection. Since the first transplant carried out in 1967, numerous advances and changes have taken place, which has made it possible to increase survival and quality of life of those who have received a new heart. In this article we review the most relevant aspects of the heart transplant and the challenges that are currently faced.

[Cell transplant and regenerative therapy with stem cells]. / Trasplante celular y terapia regenerativa con células madre.

One of the fields of medicine that has raised the most expectations in recent years is cell therapy with stem cells. The isolation of human embryo cells, the apparent and unexpected potentiality of adult stem cells and the development of gene therapy lead us to imagine a hopeful future for a significant number of diseases that are at present incurable. In this article we will sketch out the panorama of stem cell research, describing the main achievements in this field as well as some of the questions that await an answer. In spite of the great expectations, it is essential that we maintain a critical and realistic spirit when it comes to analysing the scientific advances in this area.