Regulation of mouse exploratory behaviour by irradiance and cone-opponent signals.

BACKGROUND: Animal survival depends on the ability to adjust behaviour according to environmental conditions. The circadian system plays a key role in this capability, with diel changes in the quantity (irradiance) and spectral content ('colour') of ambient illumination providing signals of time-of-day that regulate the timing of rest and activity. Light also exerts much more immediate effects on behaviour, however, that are equally important in shaping daily activity patterns. Hence, nocturnal mammals will actively avoid light and dramatically reduce their activity when light cannot be avoided. The sensory mechanisms underlying these acute effects of light are incompletely understood, particularly the importance of colour. RESULTS: To define sensory mechanisms controlling mouse behaviour, we used photoreceptor-isolating stimuli and mice with altered cone spectral sensitivity (Opn1mwR), lacking melanopsin (Opn1mwR; Opn4-/-) or cone phototransduction (Cnga3-/-) in assays of light-avoidance and activity suppression. In addition to roles for melanopsin-dependent irradiance signals, we find a major influence of spectral content in both cases. Hence, remarkably, selective increases in S-cone irradiance (producing a blue-shift in spectrum replicating twilight) drive light-seeking behaviour and promote activity. These effects are opposed by signals from longer-wavelength sensitive cones, indicating a true spectrally-opponent mechanism. Using c-Fos-mapping and multielectrode electrophysiology, we further show these effects are associated with a selective cone-opponent modulation of neural activity in the key brain site implicated in acute effects of light on behaviour, the subparaventricular zone. CONCLUSIONS: Collectively, these data reveal a mechanism whereby blue-shifts in the spectrum of environmental illumination, such as during twilight, promote mouse exploratory behaviour.

Epidemiology of bacterial co-infections and risk factors in COVID-19-hospitalized patients in Spain: a nationwide study.

BACKGROUND: We performed a nationwide population-based retrospective study to describe the epidemiology of bacterial co-infections in coronavirus disease 2019 (COVID-19)-hospitalized patients in Spain in 2020. We also analyzed the risk factors for co-infection, the etiology and the impact in the outcome. METHODS: Data were obtained from records in the Minimum Basic Data Set (MBDS) of the National Surveillance System for Hospital Data in Spain, provided by the Ministry of Health and annually published with 2 years lag. COVID-19 circulated in two waves in 2020: from its introduction to 31st June and from 1st July to 31st December. The risk of developing a healthcare-associated bacterial co-infection and the risk for in-hospital and intensive care unit (ICU) mortality in co-infected patients was assessed using an adjusted logistic regression model. RESULTS: The incidence of bacterial co-infection in COVID-19 hospitalized patients was 2.3%. The main risk factors associated with bacterial co-infection were organ failure, obesity and male sex. Co-infection was associated with worse outcomes including higher in-hospital, in-ICU mortality and higher length of stay. Gram-negative bacteria caused most infections. Causative agents were similar between waves, although higher co-infections with Pseudomonas spp. were detected in the first wave and with Haemophilus influenzae and Streptococcus pneumoniae in the second. CONCLUSIONS: Co-infections are not as common as those found in other viral respiratory infections; therefore, antibiotics should be used carefully. Screening for actual co-infection to prescribe antibiotic therapy when required should be performed.

Ability to predict the development of surgical site infection in cardiac surgery using the Australian Clinical Risk Index versus the National Nosocomial Infections Surveillance-derived Risk Index.

Surgical site infection (SSI) is a major infectious complication that increases mortality, morbidity, and healthcare costs. There are scores attempting to classify patients for calculating SSI risk. Our objectives were to validate the Australian Clinical Risk Index (ACRI) in a European population after cardiac surgery, comparing it against the National Nosocomial Infections Surveillance-derived risk index (NNIS) and analyzing the predictive power of ACRI for SSI in valvular patients. All the patients that who underwent cardiac surgery in a tertiary university hospital between 2011 and 2015 were analyzed. The patients were divided into valvular and coronary groups, excluding mixed patients. The ACRI score was validated in both groups and its ability to predict SSI was compared to the NNIS risk index. We analyzed 1,657 procedures. In the valvular patient group (n: 1119), a correlation between the ACRI score and SSI development (p < 0.05) was found; there was no such correlation with the NNIS index. The area under the receiver-operating characteristic curve (AUC) was 0.64 (confidence interval [CI] 95%, 0.5-0.7) for ACRI and 0.62 (95% CI, 0.5-0.7) for NNIS. In the coronary group (n: 281), there was a correlation between ACRI and SSI but no between NNIS and SSI. The ACRI AUC was 0.70 (95% CI, 0.5-0.8) and the NNIS AUC was 0.60 (95% CI, 0.4-0.7). The ACRI score has insufficient predictive power, although it predicts SSI development better than the NNIS index, fundamentally in coronary artery bypass grafting (CABG). Further studies analyzing determining factors are needed.

Modulation of autoimmune arthritis severity in mice by apolipoprotein E (ApoE) and cholesterol.

Apolipoprotein E (ApoE) deficiency promoted an exacerbation of autoimmune arthritis in mice by inducing proinflammatory immune responses. In this study we analysed the contribution of hypercholesterolaemia and/or the absence of ApoE anti-inflammatory properties, unrelated to its function in the control of cholesterol metabolism, towards the acceleration of arthritis in these mutant animals. The induction and severity of collagen type II-induced arthritis (CIA) were compared for B10.RIII wild-type (WT), B10.RIII.ApoE+/- , B10.RIII.ApoE-/- and B10.RIII.low-density lipoprotein receptor (LDLR-/- ) mice with different concentrations of circulating ApoE and cholesterol. A 50-70% reduction in serum levels of ApoE was observed in heterozygous B10.RIII.ApoE+/- mice in comparison to B10.RIII.WT, although both strains of mice exhibited similar circulating lipid profiles. This ApoE reduction was associated with an increased CIA severity that remained lower than in homozygous B10.RIII.ApoE-/- mice. An important rise in circulating ApoE concentration was observed in hypercholesterolaemic B10.RIII.LDLR-/- mice fed with a normal chow diet, and both parameters increased further with an atherogenic hypercholesterolaemic diet. However, the severity of CIA in B10.RIII.LDLR-/- mice was similar to that of B10.RIII.WT controls. In conclusion, by comparing the evolution of CIA between several strains of mutant mice with different levels of serum ApoE and cholesterol, our results demonstrate that both hypercholesterolaemia and ApoE regulate the intensity of in-vivo systemic autoimmune responses.

Uterine sarcoma vs adenocarcinoma: can MRI distinguish between them? / Sarcoma uterino frente a adenocarcinoma: ¿es posible distinguirlos mediante resonancia magnética?

OBJECTIVE: To analyze the MRI characteristics of uterine sarcomas (mainly carcinosarcomas) and to compare them with those of adenocarcinomas to define the findings that would be useful for the differential diagnosis. MATERIALS AND METHODS: We retrospectively reviewed the MRI studies of 13 patients with histologically diagnosed uterine sarcoma. We analyzed tumor size, signal in T2-weighted, unenhanced and gadolinium-enhanced T1-weighted, and diffusion-weighted sequences. We compared the data obtained with those of another series of 30 consecutive cases of adenocarcinomas studied with MRI. RESULTS: The sarcomas (> 9cm in 77% of cases) were considerably larger than the adenocarcinomas (p<0.001). There were no differences in FIGO staging by MRI or surgery: both tumor types were diagnosed in early stages. The signal intensity in T2-weighted images differed significantly between the two tumor types: all the sarcomas were heterogeneous and predominantly hyperintense with respect to the myometrium in T2-weighted sequences (p<0.001). In postcontrast studies, all the sarcomas showed enhancement greater than or equal to the myometrium; this finding was significantly different from the adenocarcinomas (p<0.001). In diffusion-weighted sequences, we found no significant differences in ADC values in the areas with greatest restriction, but the ADC map was more heterogeneous in the sarcomas. CONCLUSION: Uterine sarcomas do not have specific characteristics on MRI, but some findings can indicate the diagnosis. In our study, we found significant differences between sarcomas and adenocarcinomas. Sarcomas were larger, had more hyperintense and heterogeneous signal intensity in T2-weighted sequences, and enhanced more than or at least as much as the myometrium.

Epidemiology of fungal infection in COVID 19 in Spain during 2020 and 2021: a nationwide study.

We realize a nationwide population-based retrospective study to analyze the characteristics and risk factors of fungal co-infections in COVID-19 hospitalized patients as well as describe their causative agents in the Spanish population in 2020 and 2021. Data were obtained from records in the Minimum Basic Data Set of the National Surveillance System for Hospital Data in Spain, provided by the Ministry of Health, and annually published with two years lag. The assessment of the risk associated with the development of healthcare-associated fungal co-infections was assessed using an adjusted logistic regression model. The incidence of fungal co-infection in COVID-19 hospitalized patients was 1.41%. The main risk factors associated were surgery, sepsis, age, male gender, obesity, and COPD. Co-infection was associated with worse outcomes including higher in-hospital and in ICU mortality, and higher length of stay. Candida spp. and Aspergillus spp. were the microorganisms more frequent. This is the first study analyzing fungal coinfection at a national level in hospitalized patients with COVID-19 in Spanish population and one of the few studies available that demonstrate that surgery was an independent risk factor of Aspergillosis coinfection in COVID-19 patients.

Uric acid and acute kidney injury in high-risk patients for developing acute kidney injury undergoing cardiac surgery: A prospective multicenter study.

PURPOSE: It is unclear whether preoperative serum uric acid (SUA) elevation may play a role in the development of acute kidney injury (AKI) associated with cardiac surgery (CSA-AKI). We conducted a cohort study to evaluate the influence of preoperative hyperuricemia on AKI in patients at high risk for developing SC-AKI. DESIGN: Multicenter prospective international cohort study. SETTING: Fourteen university hospitals in Spain and the United Kingdom. PARTICIPANTS: We studied 261 consecutive patients at high risk of developing CSA-AKI, according to a Cleveland score ≥ 4 points, from July to December 2017. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: AKIN criteria were used for the definition of AKI. Multivariable logistic regression models and propensity score-matched pairwise analysis were used to determine the adjusted association between preoperative hyperuricemia (≥7 mg/dL) and AKI. Elevated preoperative AUS (≥7 mg/dL) was present in 190 patients (72.8%), whereas CSA-AKI occurred in 145 patients (55.5%). In multivariable logistic regression models, hyperuricemia was not associated with a significantly increased risk of AKI (adjusted Odds Ratio [OR]: 1.58; 95% confidence interval [CI]: 0.81-3; P = .17). In propensity score-matched analysis of 140 patients, the hyperuricemia group experienced similar adjusted odds of AKI (OR 1.05, 95%CI 0.93-1.19, P = .37). CONCLUSIONS: Hyperuricemia was not associated with an increased risk of AKI in this cohort of patients undergoing cardiac surgery at high risk of developing CSA-AKI.

Outbreak of Streptococcus pyogenes infection in healthcare workers in a paediatric intensive care unit: transmission from a single patient.

A 15-h stay in a paediatric intensive care unit by a girl with generalized dermal lesions superinfected with Streptococcus pyogenes led to four streptococcal infections in healthcare workers. Phenotypic and molecular analyses of the strains revealed that four isolates, characterized as emm87/ST62/T28, were identical to the isolate obtained from the index case. The occurrence of this outbreak, despite of the girl's brief hospital stay and appropriate patient management, highlights the high transmissibility of this pathogen.

Angiogenic therapy for cardiac repair based on protein delivery systems.

Cardiovascular diseases remain the first cause of morbidity and mortality in the developed countries and are a major problem not only in the western nations but also in developing countries. Current standard approaches for treating patients with ischemic heart disease include angioplasty or bypass surgery. However, a large number of patients cannot be treated using these procedures. Novel curative approaches under investigation include gene, cell, and protein therapy. This review focuses on potential growth factors for cardiac repair. The role of these growth factors in the angiogenic process and the therapeutic implications are reviewed. Issues including aspects of growth factor delivery are presented in relation to protein stability, dosage, routes, and safety matters. Finally, different approaches for controlled growth factor delivery are discussed as novel protein delivery platforms for cardiac regeneration.

Epidemiological and molecular analysis of Streptococcus pyogenes isolates causing invasive disease in Spain (1998-2009): comparison with non-invasive isolates.

The incidence, clinical manifestations, and circulating clones involved in Streptococcus pyogenes invasive disease was analyzed in two regions of Spain between 1998 and 2009. The annual average incidence of invasive disease was 2 episodes per 100,000 inhabitants (3.1 for children and 1.9 for adults). The most frequent clinical manifestations were cellulitis (41.3%), bacteremia without focus (19.0%), streptococcal toxic shock syndrome (12.6%), and pneumonia (7.7%). Among 247 invasive isolates analyzed, the most prevalent clones were emm1/ST28 (27.9%), emm3/ST15-406 (9.8%), and emm4/ST39 (6.5%). The emm1/ST28 clone was the only clone detected each year throughout the study period and was associated with more than one third of all fatal outcomes. When invasive isolates were compared with 1,189 non-invasive isolates, the emm1/ST28 clone was significantly associated with invasive disease. The speA and ssa genes were more frequent among invasive emm1 and emm4 isolates, respectively. Forty-two (17%) invasive isolates were resistant to erythromycin (21 harbored the mef gene and 21 the ermB or ermA genes). Twenty-two (8.9%) isolates had reduced susceptibility to ciprofloxacin (minimum inhibitory concentration [MIC] 2-8 µg/mL) and 32 (13%) were tetracycline-resistant (tetM or tetO gene). In conclusion, the emm1 type was overrepresented among invasive cases and was associated with high mortality rates.

Relative bioavailability study with two oral formulations of topiramate using a validated UPLC-MS/MS method.

Changes in bioavailability of anticonvulsant drugs such as topiramate may cause loss of or worsened seizure control. Thus, the purpose of this study was to evaluate, in a double-blind crossover design, the bioavailability between two oral formulations of topiramate in healthy volunteers after a single dose. The protocol, approved by the Institutional Committee of Ethics, consisted of administration of 1 tablet of 100 mg of topiramate of each formulation (Toprel and Topamax), to 20 healthy volunteers after a 12 h overnight fast, using an open, two-period, randomized, crossover and double-blind design. Thus, the plasma concentrations (Cp) of topiramate were measured at predetermined intervals of time, from 0 to 24 h, using a validated UPLC-MS/MS method. Based on plasma concentration-time profiles we obtained the following pharmacokinetic parameters: AUC(0-inf) 63,418.31 +/- 22,141.69 and 67,094.70 +/- 22,487.2 ngh/ml; AUC0-24: 30,421.02 +/- 9,964.0 and 30,489.35 +/- 9,407.17, ng x h/ml; tmax: 2.77 +/- 1.76 and 1.95 +/- 1.89 h; C(max): 2,143.33 +/- 724.26 and 2,262.51 +/- 751.12 ng/ml, for A (Toprel) and B (Topamax), respectively. All these differences were not statically significant with 90% confidence interval. The test of bioequivalence showed that Cmax, AUC(0-24) and AUC(0-inf) parameters are found within the range of 0.8 - 1.25 recommended by the FDA with a probability of bioequivalence of 100%. In accordance with these results, we can conclude that Toprel 100 mg, A (Test), is a bioequivalent generic and interchangeable with Topamax 100 mg, B (Reference).

Endothelial dysfunction is an early indicator of sepsis and neutrophil degranulation of septic shock in surgical patients.

BACKGROUND: Stratification of the severity of infection is currently based on the Sequential Organ Failure Assessment (SOFA) score, which is difficult to calculate outside the ICU. Biomarkers could help to stratify the severity of infection in surgical patients. METHODS: Levels of ten biomarkers indicating endothelial dysfunction, 22 indicating emergency granulopoiesis, and six denoting neutrophil degranulation were compared in three groups of patients in the first 12 h after diagnosis at three Spanish hospitals. RESULTS: There were 100 patients with infection, 95 with sepsis and 57 with septic shock. Seven biomarkers indicating endothelial dysfunction (mid-regional proadrenomedullin (MR-ProADM), syndecan 1, thrombomodulin, angiopoietin 2, endothelial cell-specific molecule 1, vascular cell adhesion molecule 1 and E-selectin) had stronger associations with sepsis than infection alone. MR-ProADM had the highest odds ratio (OR) in multivariable analysis (OR 11·53, 95 per cent c.i. 4·15 to 32·08; P = 0·006) and the best area under the curve (AUC) for detecting sepsis (0·86, 95 per cent c.i. 0·80 to 0·91; P < 0·001). In a comparison of sepsis with septic shock, two biomarkers of neutrophil degranulation, proteinase 3 (OR 8·09, 1·34 to 48·91; P = 0·028) and lipocalin 2 (OR 6·62, 2·47 to 17·77; P = 0·002), had the strongest association with septic shock, but lipocalin 2 exhibited the highest AUC (0·81, 0·73 to 0·90; P < 0·001). CONCLUSION: MR-ProADM and lipocalin 2 could be alternatives to the SOFA score in the detection of sepsis and septic shock respectively in surgical patients with infection.

ANTECEDENTES: La estratificación de la gravedad de una infección se basa actualmente en la puntuación SOFA (Sequential Organ Failure Assessment), que es difícil de calcular fuera de la unidad de cuidados intensivos. Los biomarcadores podrían ayudar a estratificar la gravedad de la infección en pacientes quirúrgicos. MÉTODOS: Se compararon las concentraciones de 10 biomarcadores que denotan disfunción endotelial, 22 que indican granulopoyesis de emergencia y 6 que expresan la degranulación de neutrófilos en tres grupos de pacientes de tres hospitales españoles (100 con infección, 95 con sepsis y 57 con shock séptico) en las primeras doce horas después del diagnóstico. RESULTADOS: Siete biomarcadores que expresan disfunción endotelial (proadrenomedulina, sindecan-1, trombomodulina, angiopoyetina-2, endocan-1, molécula de adhesión endotelial 1 y E-selectina) mostraron una fuerte asociación con la sepsis en comparación con la infección aislada. La proadrenomedulina presentó el valor más alto de la razón de oportunidades (odds ratio, OR) en el análisis multivariable (OR 11,53, i.c. del 95% 4,15-32,08, P = 0,006) y la mejor área bajo la curva para detectar sepsis (AUC 0,86, i.c. del 95% 0,80-0,91, P < 0,001). En la comparación entre sepsis y shock séptico, los biomarcadores que mostraron la asociación más estrecha con el shock séptico fueron dos biomarcadores de degranulación de neutrófilos (proteinasa-3 y lipocalina-2) (OR 8,09, i.c. del 9% 1,34-48,91, P = 0,028; OR 6.62, i.c. del 95% 2,47-17,77, P = 0,002), pero la lipocalina-2 presentó la mejor AUC (0,81, i.c. del 95% 0,73-0,90, P < 0,001). CONCLUSIÓN: la proadrenomedulina y la lipocalina-2 podrían representar alternativas a la puntuación SOFA para detectar sepsis y shock séptico en pacientes quirúrgicos con infección.

Effects of simvastatin on systemic inflammatory responses after cardiopulmonary bypass.

AIM: Cardiopulmonary bypass is associated with a complex systemic inflammatory response and the extent of their increase has been correlated with the development of postoperative complications. Recent studies suggest that treatment with statins is associated with a significant and marked decrease in inflammation-associated variables such as cytokines. Therefore, we investigated the effects of preoperative simvastatin treatment on systemic inflammatory response and perioperative morbidity after cardiopulmonary bypass. METHODS: A prospective, randomized study, was designed. Forty-four subjects undergoing elective coronary artery bypass grafting who fulfilled the inclusion criteria were randomized to treatment with simvastatin (20 mg/day, group A, N. 22) or control (group B, N. 22) before surgery. Plasma levels of interleukins (IL-6, IL-8, TNF-alpha), and systemic inflammatory response score (SIRS) were measured during the surgical intervention and over the following 48 postoperative hours. Cytokine levels were measured by enzyme-linked assays from plasma samples obtained at specific time points pre- and post-operation. RESULTS: In both groups the serum levels of the proinflammatory cytokines (IL-6, IL-8, TNF-alpha), and leukocytes, and the SIRS score increased significantly over the baseline, though no significant differences were observed between the two groups. The preoperative and postoperative course did not differ between both groups. CONCLUSIONS: In patients undergoing coronary artery bypass grafting with cardiopulmonary bypass, the administration of simvastatin doses not produce any changes in the inflammatory response as measured by the levels of IL-6, IL-8, TNF-alpha and SIRS score, nor does it reduce the complications after cardiac surgery.

Impact of empirical treatment with antifungal agents on survival of patients with candidemia.

OBJECTIVE: The objective of this study was to evaluate the impact of echinocandins and fluconazole) on mortality 7 and 30 days after candidemia onset and overall in-hospital mortality), in patients with candidemia at a Spanish tertiary hospital. METHODS: A retrospective study was conducted that enrolled all non-neutropenic adult patients diagnosed with candidemia at Hospital Clínico Universitario de Valladolid between 2007 and 2016. A total of 179 patients were evaluated, they were divided into two sub-groups: surviving patients (n = 92) and non-surviving patients (n = 87). RESULTS: The 7-day mortality was 25,1% (45), 30-day mortality was 46,9% (84), and overall in-hospital mortality was 48,6% (87). 40.8% of patients received no antifungal treatment (43.8% of surviving patients and 37.8% of non-surviving patients; p=0.15). A total of 106 (59.2%) patients were treated, of which 90 patients (50.3%) received empiric treatment. 19.6% and 47.8% of surviving patients were treated with echinocandins and fluconazole, respectively. By contrast, of non-surviving patients, 31.0% were treated with echinocandins and 47.1% received fluconazole. Survival for the first 7 days was significantly higher in treated with antifungal agents (log-rank = 0.029), however, there were not significant differences in 30-day survival. Factors linked to a significant increase in overall in-hospital mortality were age (OR 1.040), septic shock (OR 2.694) and need for mechanical ventilation > 48 h (OR 2.812). CONCLUSIONS: Patients who received antifungal treatment, regardless of whether they received fluconazole or echinocandins, had a significantly lower mortality rate after 7 days than untreated patients, although no significant differences in 30-day mortality were seen.

The inflammatory response to colloids and crystalloids used for pump priming during cardiopulmonary bypass.

BACKGROUND: Systemic inflammatory response frequently occurs after coronary artery bypass surgery and is strongly correlated with the risk of postoperative morbidity and mortality. This study tests the hypothesis that the priming of the extracorporeal circuit with colloid solutions results in less inflammation in patients undergoing cardiac surgery than priming with crystalloid solutions. METHODS: A prospective, randomized study was designed. Forty-four patients undergoing elective coronary artery bypass grafting were randomly allocated to one of two groups: 22 patients primed with Ringer's lactate (RL) solution and 22 patients primed with gelatin-containing solution during the surgery. Plasma levels of interleukin (IL)-6, IL-8, tumor necrosis factor (TNF)-alpha, C-reactive protein (CRP) and, complement 4 were measured during the surgical intervention and over the following 48 postoperative hours. Cytokine levels were measured by enzyme-linked assays from plasma samples obtained at specific time points pre- and post-operatively. RESULTS: In both groups the serum levels of the pro-inflammatory cytokines (IL-6, IL-8, TNF-alpha), CRP, complement 4, and leukocytes increased significantly over the baseline, although no significant differences were observed between the two groups. The operation time, blood loss, need for inotropic support, extubation time, and length of intensive care unit stay did not differ significantly between the two groups. CONCLUSION: Priming with gelatin vs. RL produces no significant differences in the inflammatory response in patients undergoing coronary artery bypass grafting with cardiopulmonary bypass.

[Central venous pressure, rewarming time, and total fluid replacement volume are predictors of mortality and complications after cardiac surgery]. / Presión venosa central, tiempo de recalentamiento y líquidos totales son factores postoperatorios de morbi-mortalidad en cirugía cardiaca.

OBJECTIVE: To analyze the influence of early (first day) postoperative factors on postoperative course in patients who have undergone heart surgery. PATIENTS AND METHODS: A cross-sectional study of consecutively enrolled heart surgery patients was designed. We recorded central venous pressure, time required for rewarming to a core temperature of 35.5degrees C, and total fluids administered in 24 hours. We then analyzed their influence on mortality and cardiac, pulmonary, and renal complications. RESULTS: Two hundred thirty-six patients were included. Central venous pressure over 18 mm Hg, time to rewarming over 6 hours, and administration of more than 5 L of fluids in the first 24 hours were factors associated with increased mortality and the development of cardiovascular, pulmonary, and renal complications. CONCLUSIONS: Central venous pressure, rewarming time, and fluid replacement volume required on the first day are predictors of postoperative course.

Antifungal treatment with echinocandins: a 10-year clinical experience.

OBJECTIVE: The number of studies evaluating the use of echinocandins, whether or not its indication meets international guidelines, in clinical practice is limited. The objective of the present study was to determine the use of echinocandins in a tertiary Spanish hospital in 10 years of clinical practice, and to evaluate its impact on prognosis. METHODS: This retrospective study involved adult nonneutropenic ill patients with suspicion of fungal invasion who started treatment with echinocandins between 2006 and 2015. RESULTS: The number of patients treated with echinocandins was 153, and candidemia was detected thereafter in 25.5%. Factors associated with in-hospital mortality in patients receiving echinocandins were: sex male, septic shock, Charlson comorbidity index, and total stay at the hospital. In-hospital mortality after 7, 30 and 90 days was 13.7%, 24.8%, and 56.8%, respectively. From patients receiving echinocandins, 98 did no show multifocal colonization, 50 had Candida score <2.5, and 49 did not meet Ostrosky-Zeichner prediction rule. A total of 19 patients did not show any of these 3 potential risk factors for candidemia. CONCLUSIONS: The use of echinocandins in 10 years of clinical practice in our tertiary hospital has been performed according to international guidelines; however, candidemia was only diagnosed thereafter in only 25.5% of cases. Furthermore, according to our results, the adequate use of echinocandins seems not to be associated with reduced mortality rates. Further studies, involving a large cohort of patients and more hospitals, are required to corroborate these results.

[Postoperative analgesia in cardiac surgery: spinal versus intravenous morphine]. / Analgesia postoperatoria en cirugía cardiaca: comparación de morfina intratecal versus morfina intravenosa.

OBJECTIVE: To compare the effects of spinal and intravenous administration of morphine to supplement anesthesia with remifentanil in terms of analgesia during early postoperative recovery and considering time until extubation. MATERIAL AND METHODS: This prospective, randomized, blinded trial enrolled 59 patients scheduled for cardiac surgery. The patients were assigned to receive either a spinal infusion of morphine (15 microg x Kg(-1)) or an intravenous infusion (0.3 mg x Kg(-1)). Anesthesia was maintained with 0.15 to 0.50 microg x Kg(-1) x min(-1) of remifentanil and 2 to 4 mg x Kg(-1) x h(-1) of propofol in perfusion. After the period of extracorporeal circulation, all patients were given an intravenous infusion of 30 mg of ketorolac. Later intravenous ketorolac was ministered at a dose of 30 mg per 8 hours; intravenous morphine (bolus dose of 3 mg) was also administered until pain was relieved. RESULTS: The same quality of postoperative analgesia and anesthetic recovery was achieved with both spinal and intravenous administration. The incidence of side effects was also similar. Likewise, the extubation times were similar in the 2 groups (spinal infusion group: 294.5 [SD, 150.5] minutes; intravenous group: 325.0 [139.9] minutes; P>0.05). Less postoperative intravenous morphine was administered in the first 24 hours to patients in the spinal morphine group (P<0.05) and fewer patients in that group required intravenous morphine boluses (P<0.05). CONCLUSIONS: Our study suggests that spinal morphine does not offer advantages over intravenous morphine with regard to postoperative analgesia, hemodynamic stability and respiratory parameters, time until extubation, or adverse effects.

Preclinical studies of the combination of mafosfamide (Asta-Z 7654) and etoposide (VP-16-213) for purging leukemic autologous marrow.

In the present study we evaluated the effect of etoposide (VP-16-213) compared to mafosfamide-cyclohexylamine (Asta-Z 7654) on normal granulocyte-macrophage colony-forming unit (GM-CFU) growth, T-cell response to mitogens, and a clonogenic promyelocytic cell line (HL-60). The incubation time (30 min vs 60 min) appeared to be a fundamental parameter. The GM-CFU recovery was 14.4% +/- 7.3% and 1.4% +/- 2.3%, respectively, at 50 micrograms/ml Asta-Z 7654, and 17.6% +/- 8.6% and 3.00% +/- 2.4%, respectively, at 50 micrograms/ml VP-16. ASTA-Z at 50 micrograms/ml was effective in inhibiting the T-cell response to phytohemagglutinin (98.7% +/- 1.2%), whereas VP-16 was not (2.3% +/- 1.7%). With the combined chemical agents ranging from 10 to 20 micrograms/ml for each drug, we obtained a better GM-CFU recovery (five to ten times) using a middle term liquid culture (21-day incubation) than with the standard colony assay (plated immediately after treatment). When using HL-60 cells as the target, the antileukemic activity of VP-16 was lower than of Asta-Z 7654. Both compounds, at 20 micrograms/ml, resulted in 3.3- and 2.3-log cell killing, respectively. On the other hand, lower doses of Asta-Z 7654 combined with VP-16 (ranging from 10 to 15 micrograms/ml each) induced greater than 4-log cell killing after 60 min incubation time. These data suggest that VP-16 could be combined with Asta-Z provided that the dose is reduced for both drugs (less than 20 micrograms/ml).