HLA genetic polymorphisms and prognosis of patients with COVID-19.

Objective: Different genetic polymorphisms of human leukocyte antigen (HLA) have been associated with the risk and prognosis of autoimmune and infectious diseases. The objectives of this study were to determine whether there is an association between HLA genetic polymorphisms and the susceptibility to and mortality of coronavirus disease 2019 (COVID-19) patients. Design: Observational and prospective study. Setting: Eight Intensive Care Units (ICU) from 6 hospitals of Canary Islands (Spain). Patients: COVID-19 patients admitted in ICU and healthy subjects. Interventions: Determination of HLA genetic polymorphisms. Main variable of interest: Mortality at 30 days. Results: A total of 3886 healthy controls and 72 COVID-19 patients (10 non-survivors and 62 survivor patients at 30 days) were included. We found a trend to a higher rate of the alleles HLA-A*32 (p = 0.004) in healthy controls than in COVID-19 patients, and of the alleles HLA-B*39 (p = 0.02) and HLA-C*16 (p = 0.02) in COVID-19 patients than in healthy controls; however, all these p-values were not significant after correction for multiple comparisons. Logistic regression analysis showed that the presence of certain alleles was associated with higher mortality, such as the allele HLA-A*11 after controlling for SOFA (OR = 7.693; 95% CI = 1.063-55.650; p = 0.04) or APACHE-II (OR = 11.858; 95% CI = 1.524-92.273; p = 0.02), the allele HLA-C*01 after controlling for SOFA (OR = 11.182; 95% CI = 1.053-118.700; p = 0.04) or APACHE-II (OR = 17.604; 95% CI = 1.629-190.211; p = 0.02), and the allele HLA-DQB1*04 after controlling for SOFA (OR = 9.963; 95% CI = 1.235-80.358; p = 0.03). Conclusions: The new finding from our preliminary study of small sample size was that HLA genetic polymorphisms could be associated with COVID-19 mortality; however, studies with a larger sample size before definitive conclusions can be drawn.

Objetivo: Diferentes polimorfismos genéticos de los antígenos leucocitarios humanos (HLA) están asociados con el riesgo y el pronóstico de enfermedades autoinmunes e infecciosas. Los objetivos de estudio fueron determinar si existe una asociación entre polimorfismos genéticos de HLA y la susceptibilidad y mortalidad de pacientes con la enfermedad del coronavirus 2019 (COVID-19). Diseño: Estudio observacional y prospectivo. Ámbito: Ocho unidades de cuidados intensivos (UCI) de 6 hospitales de las Islas Canarias (España). Pacientes: Pacientes COVID-19 ingresados en la UCI y sujetos sanos. Intervenciones: Se determinaron los polimorfismos genéticos de los HLA. Variable de interés principal: Mortalidad a los 30 días. Resultados: Se incluyeron 3.886 sujetos sanos y 72 pacientes COVID-19 (10 fallecidos y 62 supervivientes a 30 días). Encontramos una tendencia a una mayor frecuencia de los alelos HLA-A*32 (p = 0,004) en sujetos sanos que en pacientes COVID-19, y de los alelos HLA-B*39 (p = 0,02) y HLA-C*16 (p = 0,02) en pacientes COVID-19 que en sujetos sanos; sin embargo, no fueron significativos al corregir por comparaciones múltiples. En la regresión logística encontramos que la presencia de ciertos alelos estuvo asociada con mayor mortalidad, como el alelo HLA-A*11 controlando por SOFA (OR= 7.693; IC del 95%= 1.063-55.650; p = 0,04) o APACHE-II (OR= 11.858; IC del 95%= 1.524-92.273; p = 0,02), el alelo HLA-C*01 controlando por SOFA (OR= 11.182; IC del 95%= 1.053-118.700; p = 0,04) o APACHE-II (OR= 17.604; IC del 95%= 1.629-190.211; p = 0,02) y el alelo HLA-DQB1*04 controlando por SOFA (OR= 9.963; IC del 95%= 1.235-80.358; p = 0,03). Conclusiones: Los nuevos hallazgos de nuestro preliminar estudio de pequeño tamaño muestral fueron que determinados polimorfismos genéticos de los HLA podrían estar asociados con la mortalidad de pacientes COVID-19; sin embargo, son necesarios estudios de mayor tamaño muestral para concluirlo definitivamente.

Sustained high serum caspase-3 concentrations and mortality in septic patients.

Caspase-3 is the main executor of the apoptotic process. Higher serum caspase-3 concentrations in non-survivor compared to survivor septic patients have been found. The objectives of this work (with the increase of sample size to 308 patients, and the determination of serum caspase-3 concentrations also on days 4 and 8 of diagnosis of severe sepsis) were to know whether an association between serum caspase-3 concentrationss during the first week, degree of apoptosis, sepsis severity, and sepsis mortality exists. We collected serum samples of 308 patients with severe sepsis from eight intensive care units on days 1, 4 and 8 to measure concentrations of caspase-3 and caspase-cleaved cytokeratin (CCCK)-18 (to assess degree of apoptosis). End point was 30-day mortality. We found higher serum concentrations of caspase-3 and CCCK-18 in non-survivors compared to survivors on days 1 (p < 0.001), 4 (p < 0.001), and 8 (p < 0.001). We found an association between serum caspase-3 concentrations on days 1, 4 and 8 of severe sepsis diagnosis and serum CCCK-18 concentrations (p < 0.001), SOFA (p < 0.001), serum acid lactic concentrations (p < 0.001), and 30-day sepsis mortality (p < 0.001). The new findings of this work were that an association between serum caspase-3 concentrations during the first week, apoptosis degree, sepsis severity, and sepsis mortality exists.

Guidelines for the prevention of ventilator-associated pneumonia and their implementation. The Spanish "Zero-VAP" bundle.

BACKGROUND: "Zero-VAP" is a proposal for the implementation of a simultaneous multimodal intervention in Spanish intensive care units (ICU) consisting of a bundle of ventilator-associated pneumonia (VAP) prevention measures. METHODS/DESIGN: An initiative of the Spanish Societies of Intensive Care Medicine and of Intensive Care Nurses, the project is supported by the Spanish Ministry of Health, and participation is voluntary. In addition to guidelines for VAP prevention, the "Zero-VAP" Project incorporates an integral patient safety program and continuous online validation of the application of the bundle. For the latter, VAP episodes and participation indices are entered into the web-based Spanish ICU Infection Surveillance Program "ENVIN-HELICS" database, which provides continuous information about local, regional and national VAP incidence rates. Implementation of the guidelines aims at the reduction of VAP to less than 9 episodes per 1000 days of mechanical ventilation. A total of 35 preventive measures were initially selected. A task force of experts used the Grading of Recommendations, Assessment, Development and Evaluation Working Group methodology to generate a list of 7 basic "mandatory" recommendations (education and training in airway management, strict hand hygiene for airway management, cuff pressure control, oral hygiene with chlorhexidine, semi-recumbent positioning, promoting measures that safely avoid or reduce time on ventilator, and discouraging scheduled changes of ventilator circuits, humidifiers and endotracheal tubes) and 3 additional "highly recommended" measures (selective decontamination of the digestive tract, aspiration of subglottic secretions, and a short course of iv antibiotic). DISCUSSION: We present the Spanish VAP prevention guidelines and describe the methodology used for the selection and implementation of the recommendations and the organizational structure of the project. Compared to conventional guideline documents, the associated safety assurance program, the online data recording and compliance control systems, as well as the existence of a pre-defined objective are the distinct features of "Zero VAP".

Prospective study on loss of signal on the first side during neuromonitoring of the recurrent laryngeal nerve in total thyroidectomy.

BACKGROUND: Staged thyroidectomy has been recommended when loss of the signal from intraoperative nerve monitoring is observed after first-side dissection of the recurrent laryngeal nerve. There is no high-quality evidence supporting this recommendation. In addition, it is not clear whether signal loss predicts postoperative vocal cord paralysis. METHODS: This was a prospective observational study of consecutive adult patients undergoing neuromonitored total thyroidectomy for either malignancy or multinodular goitre. The prevalence of first-side loss of signal was recorded. Surgery was completed, and vagus and laryngeal nerves on the first side were rechecked at the end of the procedure. RESULTS: Two-hundred and ninety patients were included. Loss of signal on the first side was noted in 16 procedures (5.5 per cent). Thyroidectomy was completed and, at retesting, 15 of 16 initially silent nerves recovered an electromyographic signal with a mean(s.d.) amplitude of 132(26) mcV. Mean time to recovery was 20.2 (range 10-35) min. In no patient was the signal lost on the opposite side. Only three of 15 nerves with a recovered signal were associated with transient vocal cord dysfunction. CONCLUSION: After loss of signal of the recurrent laryngeal nerve dissected initially, there was a 90 per cent chance of intraoperative signal recovery. In this setting, judicious bilateral thyroidectomy can be performed without risk of bilateral recurrent nerve paresis.

Lesser incidence of accidental catheter removal with femoral versus radial arterial access.

BACKGROUND: Arterial catheterization is a frequent procedure in Intensive Care Units (ICUs). Accidental catheter removal (ACR) can cause severe and potentially life-threatening complications such as severe bleeding and vascular damage. Few data are available on accidental arterial catheter removal, and no studies have been found comparing the incidence of ACR between different arterial catheter sites. OBJECTIVE: To compare the incidence of ACR in femoral and radial arterial catheters. RESEARCH DESIGN: Retrospective study. SETTING: A polyvalent ICU. SUBJECTS: All consecutive patients subjected to femoral or radial arterial catheterization. MEASURES: The incidence of ACR per 100 catheter-days between groups was compared using Poisson regression. We considered ACR as the presence of unintended removal produced by the patient or healthcare personnel. RESULTS: A total of 2419 radial and 1085 femoral arterial catheters were inserted and remained in situ during 14,742 and 6497 days, respectively. We detected 45 cases of ACR with the femoral access and 162 cases with the radial access. The ACR rate was lower with the femoral access (4.1% vs 6.7% in the case of the radial access; p=0.003). Poisson regression analysis confirmed a lower incidence of ACR with the femoral versus the radial access (0.69 vs 1.10 ACR events per 100 catheter-days; OR 0.6, p=0.006, CI95% 0.01-0.83). CONCLUSIONS: The incidence of ACR was found to be lower with the femoral than with the radial arterial catheters. In order to improve patient safety, it could be interesting to exhaustively monitor the incidence of ACR and adopt preventive measures, since ACR can give rise to serious complications.

Association between septic patient mortality and blood survivin concentrations.

OBJECTIVE: Survivin is a member of inhibitors of apoptosis proteins family. There are not data about the association between mortality of septic patients and blood survivin concentrations. Therefore, the objective of this study was to determine whether exist that association. DESIGN: Observational and prospective study. SETTING: Three Spanish Intensive Care Units. PATIENTS: Patients with sepsis or septic shock according to Sepsis-3 Consensus criteria. INTERVENTIONS: Serum survivin concentrations were determined at moment of sepsis diagnosis. MAIN VARIABLE OF INTEREST: Mortality at 30 days. RESULTS: A total of 204 patients were included in the study, of which 75 (36.8%) died in the first 30 days. Lower age (p<0.001), serum lactic acid levels (p=0.001), rate of septic shock (p=0.001) and SOFA (p<0.001), and higher serum survivin levels (p=0.001) exhibited surviving (n=129) than non-surviving patients (n=75). We found in multiple logistic regression analysis an association between serum survivin concentrations and mortality independently of SOFA, lactic acid, age, INR, activated partial thromboplastin time (aPTT) and empiric antimicrobial treatment adequate (OR=0.968; 95% CI=0.946-0.990; p=0.005), and also independently of APACHE-II, lactic acid, platelet, INR, aPTT and empiric antimicrobial treatment adequate (OR=0.966; 95% CI=0.943-0.989; p=0.004). CONCLUSIONS: There is an association between septic patient mortality and low blood survivin concentrations.

Patient safety in magnetic resonance imaging.

Image acquisition involves the use of static magnetic fields, field gradients and radiofrequency waves. These elements make the MRI a different modality. More and more centers work with 3.0 T equipment that present higher risks for the patient, compared to those of 1.5 T. Therefore, there is a need for updating for radiology staff that allows them to understand the risks and reduce them, since serious and even fatal incidents can occur. The objective of this work is to present a review and update of the risks to which patients are subjected during the performance of a magnetic resonance imaging (MRI) study.

Long-term results of biopsy-guided selection and allocation of kidneys from older donors in older recipients.

In our old-for-old program, we discard or allocate older extended criteria donor kidneys to single (SKT) or dual kidney transplantation (DKT) depending on histological Remuzzi's score in recipients older than 60 years. Here, we analyze the long-term results of this program and try to identify independent predictors of patient and graft survival. Between December 1996 and January 2008, we performed 115 SKT and 88 DKT. Discard rate was 15%. Acute rejection incidence was higher in SKT than in DKT (22.6% vs. 11.4%, p = 0.04). Renal function was better in DKT than in SKT up to 5 years after transplantation. Surgical complications were frequent in DKT. Ten-year cumulative graft survival was significantly lower in the SKT group (31% vs. 53%, p = 0.03). In SKT, histological score 4 provided similar graft survival than 3 or less, whereas in DKT score 4, 5 or 6 displayed similar outcome. Finally, independent predictors of graft survival were history of major adverse cardiac event and 1-year serum creatinine, rather than SKT or DKT. In conclusion, this biopsy-guided old-for-old strategy resulted in acceptable long-term graft survival. Our results suggest that DKT should be considered for scores of 5 or 6 only.

Lower catheter-related bloodstream infection in arterial than in venous femoral catheter.

In previous studies no differences were found in catheter-related bloodstream infection (CRBSI) between arterial and venous catheters. However, the distribution of each venous and arterial site could influence the results as in some studies a higher CRBSI incidence in venous and arterial femoral accesses has been found than in other venous and arterial accesses. Possibly, to eliminate this confounding, it might be more appropriate to compare the CRBSI incidence between arterial and venous catheters in the same site as the femoral access. Thus, the objective of this study was to compare the incidence of CRBSI between 618 arterial and 288 venous femoral accesses. We found higher CRBSI incidence in venous than in arterial femoral catheters (8.34 vs 1.92 CRBSI episodes/1,000 catheter-days; P < 0.001). Exact logistic regression analysis showed that venous femoral catheters had a higher risk of CRBSI than arterial femoral catheters (OR = 1.02; 95%CI =1.01-infinite; P < 0.001) controlled by APACHE-II score and duration of the catheter. The novel finding of our study is that the risk of CRBSI was higher in venous than in arterial femoral catheters. Thus, special approaches to prevent CRBSI might play a more important role in venous than in arterial catheters.

Rifampicin-miconazole-impregnated catheters save cost in jugular venous sites with tracheostomy.

Antimicrobial-impregnated catheters are more expensive than standard catheters (S-C). A higher incidence of catheter-related bloodstream infection (CRBSI) has been found in jugular venous access with tracheostomy than without tracheostomy. The objective of this study was to determine central venous catheter (CVC)-related costs (considering only the cost of the CVC, diagnosis of CRBSI, and antimicrobial agents used to treat CRBSI) using rifampicin-miconazole-impregnated catheters (RM-C) or S-C in jugular venous access with tracheostomy. We performed a retrospective cohort study of patients admitted to the intensive care unit (ICU) with tracheostomy who received one or more jugular venous catheters. RM-C showed a lower incidence of CRBSI compared with S-C (0 vs. 20.16 CRBSI episodes/1,000 catheter-days; odds ratio=0.05; 95% confidence interval=0.001-0.32; p<0.001) and lower CVC-related costs (including the cost of the CVC, diagnosis, and treatment of CRBSI) (11.46 ± 6.25 vs. 38.11 ± 77.25; p<0.001) in jugular venous access with tracheostomy. The use of RM-C could reduce CVC-related costs in jugular venous access with tracheostomy. The results of our study may contribute to clinical decision-making and selection of those patients who could benefit from the use of antimicrobial-impregnated catheters.

Ventilator-associated pneumonia with or without toothbrushing: a randomized controlled trial.

Certain guidelines for the prevention of ventilator-associated pneumonia (VAP) recommend oral care with chlorhexidine, but none refer to the use of a toothbrush for oral hygiene. The role of toothbrush use has received scant attention. Thus, the objective of this study was to compare the incidence of VAP in critical care patients receiving oral care with and without manual brushing of the teeth. This was a randomized clinical trial developed in a 24-bed medical-surgical intensive care unit (ICU). Patients undergoing invasive mechanical ventilation for than 24 h were included. Patients were randomly assigned to receive oral care with or without toothbrushing. All patients received oral care with 0.12 % chlorhexidine digluconate. Tracheal aspirate samples were obtained during endotracheal intubation, then twice a week, and, finally, on extubation. There were no significant differences between the two groups of patients in the baseline characteristics. We found no statistically significant differences between the groups regarding the incidence of VAP (21 of 217 [9.7 %] with toothbrushing vs. 24 of 219 [11.0 %] without toothbrushing; odds ratio [OR] = 0.87, 95 % confidence interval [CI] = 0.469-1.615; p = 0.75). Adding manual toothbrushing to chlorhexidine oral care does not help to prevent VAP in critical care patients on mechanical ventilation.

[Recommendations of the Infectious Diseases Work Group (GTEI) of the Spanish Society of Intensive and Critical Care Medicine and Coronary Units (SEMICYUC) and the Infections in Critically Ill Patients Study Group (GEIPC) of the Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC) for the diagnosis and treatment of influenza A/H1N1 in seriously ill adults admitted to the Intensive Care Unit]. / Recomendaciones del Grupo de Trabajo Enfermedades Infecciosas (GTEI) de la Sociedad Española de Medicina Intensiva, Crítica y Unidades Coronarias (SEMICYUC) y el Grupo de Estudio de Infecciones en el Paciente Crítico (GEIPC) de la Sociedad Española de Enfermedades Infecciosas y Microbiología clínica (SEIMC) para el diagnóstico y tratamiento de la gripe A/H1N1 en pacientes adultos graves hospitalizados en las Unidades de Cuidados Intensivos.

The diagnosis of influenza A/H1N1 is mainly clinical, particularly during peak or seasonal flu outbreaks. A diagnostic test should be performed in all patients with fever and flu symptoms that require hospitalization. The respiratory sample (nasal or pharyngeal exudate or deeper sample in intubated patients) should be obtained as soon as possible, with the immediate start of empirical antiviral treatment. Molecular methods based on nucleic acid amplification techniques (RT-PCR) are the gold standard for the diagnosis of influenza A/H1N1. Immunochromatographic methods have low sensitivity; a negative result therefore does not rule out active infection. Classical culture is slow and has low sensitivity. Direct immunofluorescence offers a sensitivity of 90%, but requires a sample of high quality. Indirect methods for detecting antibodies are only of epidemiological interest. Patients with A/H1N1 flu may have relative leukopenia and elevated serum levels of LDH, CPK and CRP, but none of these variables are independently associated to the prognosis. However, plasma LDH> 1500 IU/L, and the presence of thrombocytopenia <150 x 10(9)/L, could define a patient population at risk of suffering serious complications. Antiviral administration (oseltamivir) should start early (<48 h from the onset of symptoms), with a dose of 75 mg every 12h, and with a duration of at least 7 days or until clinical improvement is observed. Early antiviral administration is associated to improved survival in critically ill patients. New antiviral drugs, especially those formulated for intravenous administration, may be the best choice in future epidemics. Patients with a high suspicion of influenza A/H1N1 infection must continue with antiviral treatment, regardless of the negative results of initial tests, unless an alternative diagnosis can be established or clinical criteria suggest a low probability of influenza. In patients with influenza A/H1N1 pneumonia, empirical antibiotic therapy should be provided due to the possibility of bacterial coinfection. A beta-lactam plus a macrolide should be administered as soon as possible. The microbiological findings and clinical or laboratory test variables may decide withdrawal or not of antibiotic treatment. Pneumococcal vaccination is recommended as a preventive measure in the population at risk of suffering severe complications. Although the use of moderate- or low-dose corticosteroids has been proposed for the treatment of influenza A/H1N1 pneumonia, the existing scientific evidence is not sufficient to recommend the use of corticosteroids in these patients. The treatment of acute respiratory distress syndrome in patients with influenza A/H1N1 must be based on the use of a protective ventilatory strategy (tidal volume <10 ml / kg and plateau pressure <35 mmHg) and positive end-expiratory pressure set to high patient lung mechanics, combined with the use of prone ventilation, muscle relaxation and recruitment maneuvers. Noninvasive mechanical ventilation cannot be considered a technique of choice in patients with acute respiratory distress syndrome, though it may be useful in experienced centers and in cases of respiratory failure associated with chronic obstructive pulmonary disease exacerbation or heart failure. Extracorporeal membrane oxygenation is a rescue technique in refractory acute respiratory distress syndrome due to influenza A/H1N1 infection. The scientific evidence is weak, however, and extracorporeal membrane oxygenation is not the technique of choice. Extracorporeal membrane oxygenation will be advisable if all other options have failed to improve oxygenation. The centralization of extracorporeal membrane oxygenation in referral hospitals is recommended. Clinical findings show 50-60% survival rates in patients treated with this technique. Cardiovascular complications of influenza A/H1N1 are common. Such problems may appear due to the deterioration of pre-existing cardiomyopathy, myocarditis, ischemic heart disease and right ventricular dysfunction. Early diagnosis and adequate monitoring allow the start of effective treatment, and in severe cases help decide the use of circulatory support systems. Influenza vaccination is recommended for all patients at risk. This indication in turn could be extended to all subjects over 6 months of age, unless contraindicated. Children should receive two doses (one per month). Immunocompromised patients and the population at risk should receive one dose and another dose annually. The frequency of adverse effects of the vaccine against A/H1N1 flu is similar to that of seasonal flu. Chemoprophylaxis must always be considered a supplement to vaccination, and is indicated in people at high risk of complications, as well in healthcare personnel who have been exposed.

Association between blood caspase-8 levels and mortality of patients with malignant middle cerebral artery infarction.

OBJECTIVE: High concentrations of caspase-8 (main initiator caspase of apoptosis extrinsic pathway) have been found in brain tissue from traumatic brain injury patients and in blood of patients with different diseases. However, there are not data on blood caspase-8 concentrations in ischemic stroke patients. Therefore, the objective of this study was to determine whether there is an association between blood caspase-8 concentrations and the probability and speed of mortality at 30 days in patients with malignant middle cerebral artery infarction (MMCAI). DESIGN: Observational prospective study. SETTING: Five Intensive Care Units (ICU). PATIENTS: Patients with severe malignant middle cerebral artery infarction (MMCAI) defined as acute infarction in more than of 50% of that territory and Glasgow Coma Scale (GCS)<9. INTERVENTIONS: Determination of serum caspase-8 levels when MMCAI was diagnosed. MAIN VARIABLES OF INTEREST: Mortality at 30 days and time until this event. RESULTS: Severe MMCAI patients (n=28) compared to survivor patients (n=28) showed higher serum caspase-8 concentrations (p<0.001), lower platelet count (p=0.01) and lower GCS (p=0.002). We found an area under the curve for mortality prediction of 78% (95% CI=65%-91%; p<0.001) by serum caspase-8 levels. Kaplan-Meier analysis found higher mortality rate in patients with serum caspase-8 levels >62.8ng/mL (hazard ratio=11.2; 95% CI=4.4-28.4; p<0.001). CONCLUSIONS: The association of high blood caspase-8 concentrations with the rate and the velocity of 30-day mortality in MMCAI patients is the main new finding of our study.

High serum nitrates levels in non-survivor COVID-19 patients.

OBJECTIVE: Higher blood nitrate and nitrite levels have been found in coronavirus disease 2019 (COVID-19) patients than in healthy subjects. The present study explores the potential association between serum nitrate levels and mortality in COVID-19 patients. DESIGN: A prospective observation study was carried out. SETTING: Eight Intensive Care Units (ICUs) from 6 hospitals in the Canary Islands (Spain). PATIENTS: COVID-19 patients admitted to the ICU. INTERVENTIONS: Determination of serum nitrate levels at ICU admission. MAIN VARIABLE OF INTEREST: Mortality at 30 days. RESULTS: Non-surviving (n=11) compared to surviving patients (n=42) showed higher APACHE-II (p<0.001) and SOFA scores (p=0.004), and higher serum nitrate levels (p=0.001). Logistic regression analyses showed serum nitrate levels to be associated to 30-day mortality after controlling for SOFA (OR=1.021; 95%CI=1.006-1.036; p=0.01) or APACHE-II (OR=1.023; 95%CI=1.006-1.041; p=0.01). There were no differences in the area under the curve (AUC) for mortality prediction by serum nitrate levels (AUC=83%; 95%CI=73-92%; p<0.001), APACHE II (AUC=85%; 95%CI=75-96%; p<0.001) and SOFA (AUC=78%; 95%CI=63-92%; p=0.005) based on the DeLong method. The Kaplan-Meier analysis found patients with serum nitrates levels>68.4µmol/l to have a higher mortality rate (hazard ratio=138.8; 95%CI=22.3-863.9; p<0.001). CONCLUSIONS: The main novel finding was the association between serum nitrate levels and mortality in COVID-19 patients controlling for the SOFA or APACHE-II scores, though larger studies are needed to confirm this observation.

Sonication did not provide reliability to Maki technique for catheter related bloodstream infection diagnosis.

OBJECTIVE: The aim of our study was to analyze sonication and Maki techniques for diagnosis of catheter tip colonization and catheter-related bloodstream infection (CRBSI) on patients admitted to ICU. METHODS: Observational and prospective study in one Intensive Care Unit. Patients with some central venous catheter (CVC) at least for 7 days and catheter-related infection (CRI) suspicion (new episode of fever or sepsis) were included. We performed Maki technique followed by sonication of catheter tip. We compared area under the curve (AUC) of Maki, sonication, and techniques combination to diagnosis catheter tip colonization and CRBSI. RESULTS: We included 94 CVC from 87 CRI suspicion episodes. We found 14 cases of catheter tip colonization and 10 cases of CRBSI. Of the 14 catheter tip colonization cases, 7 (50.0%) were detected by Maki and sonication techniques, 6 (42.9%) were detected only by Maki technique, and 1 (7.1%) was detected only by sonication technique. Of the 10 CRBSI, 6 (60.0%) were detected by Maki and sonication techniques, 4 (40.0%) were detected only by Maki technique, and any only by sonication technique. We found higher AUC in Maki technique than in sonication technique to diagnosis of CRBSI (p=0.02) and to diagnosis of catheter tip colonization (p=0.03). No significant differences were found in AUC between Maki technique and combination techniques for diagnosis of catheter tip colonization (p=0.32) and of CRBSI (p=0.32). CONCLUSIONS: Sonication did not provide reliability to Maki technique for diagnosis of catheter tip colonization and CRBSI.

Blood caspase-8 concentrations and mortality among septic patients.

OBJECTIVE: No data are available on blood caspase-8 concentrations (the initiator caspase in the extrinsic apoptosis pathway) in septic patients. The present study thus describes the blood caspase-8 concentrations in survivors and non-survivors, and examines the possible association between blood caspase-8 concentrations and mortality in septic patients. DESIGN: A prospective observational study was carried out. SETTING: Three Spanish Intensive Care Units. PATIENTS: Septic patients. INTERVENTIONS: Serum caspase-8 concentrations were determined at the diagnosis of sepsis. MAIN VARIABLE OF INTEREST: Mortality after 30 days. RESULTS: Patients not surviving at day 30 (n=81) compared to surviving patients (n=140) showed higher serum caspase-8 levels (p<0.001). Multiple logistic regression analysis found an association between serum caspase-8 levels>43.5ng/ml and mortality (OR=3.306; 95%CI=1.619-6.753; p=0.001). The area under the curve (AUC) for mortality predicted by serum caspase-8 levels was 67% (95% CI=60-73%; p<0.001). CONCLUSIONS: The novel findings of our study were that blood caspase-8 concentrations are higher in non-survivors than in survivors, and that there is an association between blood caspase-8 concentrations and mortality in septic patients.

Influence of tracheostomy on the incidence of catheter-related bloodstream infection in the catheterization of jugular vein by posterior access.

There are no data about the influence of tracheostomy in the incidence of catheter-related bloodstream infection (CRBSI) on the catheterization of the jugular vein by posterior access and there are no recommendations relating to this circumstance in the guidelines of the Centers for Disease Control and Prevention (CDC) and of Healthcare Epidemiology of America/Infectious Diseases Society of America (SHEA/IDSA) for the prevention of CRBSI. The novel finding of this observational study was that there was a higher incidence of CRBSI in the catheterization of jugular vein by posterior access in patients with tracheostomy than without it (13.24 vs 0 episodes of CRBSI per 1,000 catheter-day; odds ratio = 23.92; 95% CI = 1.86-infinite; p = 0.008). Thus, the presence of tracheostomy is a risk factor of CRBSI on the catheterization of jugular vein by posterior access.

[Opioids for chronic noncancer pain: recommendations based on clinical practice guidelines]. / Uso de opioides en el tratamiento del dolor crónico no oncológico. Recomendaciones basadas en las guías de práctica clínica.

OBJECTIVE: The need for major opioids in the treatment of chronic pain unrelated to cancer is increasing. We therefore appraised available clinical practice guidelines in order to identify recommendations for good practice in the use of these drugs. MATERIAL AND METHODS: By searching the main guideline repositories as well as resources provided by medical associations, we identified clinical practice guidelines on the use of major opioids published up to 2007. Fourteen of the 28 guidelines we found met the inclusion criteria. To appraise the guidelines we applied the criteria for scientific evidence of the AGREE collaboration (Appraisal of Guidelines Research and Evaluation). The AGREE instrument consists of 23 items organized in 6 areas for appraisal. RESULTS: Of the 14 guidelines appraised, 5 were judged to be of high quality. In each of the 5 selected guidelines, the relation between a recommendation and the evidence it was based on was stated explicitly; all 5 had overall quality scores over 60%. The recommendations drawn from these guidelines deal with 3 sequential moments in the use of opioids: start of treatment, maintenance therapy, and withdrawal of the drug. CONCLUSION: The use of opioids to treat chronic noncancer pain is controversial in terms of effectiveness, safety, and the possibility of addiction or abuse. The opioid should be indicated for the pain and prescribed with caution; each case should be assessed individually. Following the recommendations drawn from these guidelines will be important for achieving control of both pain and the accompanying symptoms. The use of major opioids to relieve chronic pain unrelated to cancer, and therefore to improve the quality of life of patients who experience this type of pain, is a legitimate treatment approach.

DNA and RNA oxidative damage are associated to mortality in patients with cerebral infarction.

OBJECTIVE: Secondary injury due to oxidation may occur during ischemic stroke, possibly leading to oxidative damage to deoxyribonucleic acid (DNA) and ribonucleic acid (RNA). Higher blood concentrations of 8-hydroxy-2'-deoxyguanosine (8-OHdG) (through the oxidation of guanosine from DNA) have been found in ischemic stroke patients than in healthy subjects, and in patients with versus without post-ischemic stroke depression. The present study was carried out to explore the possible association between serum DNA and RNA oxidative damage and mortality in patients with cerebral infarction. METHODS: A prospective, multicenter observational study was carried out in the Intensive Care Units of 6 Spanish hospitals. We included patients with severe malignant middle cerebral artery infarction (MMCAI) defined as ischemic changes evidenced by computed tomography in more than 50% of the middle cerebral artery territory and a Glasgow Coma Score (GCS)<9. Serum concentrations of the three oxidized guanine species (OGS) (8-hydroxyguanine from DNA or RNA, 8-hydroxyguanosine from RNA, and 8-OHdG from DNA) on the day of MMCAI diagnosis were determined. The study endpoint was 30-day mortality. RESULTS: We found higher serum OGS levels (p<0.001) in non-surviving (n=34) than in surviving patients (n=34). Logistic regression analyses showed serum OGS levels to be associated to 30-day mortality controlling for lactic acid, GCS and platelet count (OR=1.568; 95%CI=1.131-2.174; p=0.01). CONCLUSIONS: The novel observation in this study is the association between global serum OGS concentration and mortality in ischemic stroke patients.

Serum caspase-3 levels during the first week of traumatic brain injury.

OBJECTIVE: Confluence between the intrinsic and extrinsic apoptosis pathways is reached at the point of caspase-3 activation, which induces death cell. Higher serum caspase-3 levels have been recorded on day 1 of traumatic brain injury (TBI) in 30-day non-survivors compared to survivors. The objectives of this study therefore were to determine whether serum caspase-3 levels are persistently higher in non-survivors than in survivors, and whether these levels may be used to predict 30-day mortality. DESIGN: A prospective observational study was carried out. SETTING: Six Spanish Intensive Care Units. PATIENTS: Patients with severe isolated TBI (defined as Glasgow Coma Scale <9 points and non-cranial Injury Severity Score <10 points). INTERVENTIONS: Serum caspase-3 concentrations were measured on days 1, 4 and 8 of TBI. MAIN VARIABLES OF INTEREST: Thirty-day mortality was considered as the study endpoint. RESULTS: In comparison with non-survivors (n=34), 30-day survivors (n=90) showed lower serum caspase-3 levels on days 1 (p=0.001), 4 (p<0.001) and 8 (p<0.001) of TBI. Analysis of the ROC curves showed serum caspase-3 concentrations on days 1, 4 and 8 of TBI to have an AUC (95% CI) in predicting 30-day mortality of 0.70 (0.61-0.78; p=0.001), 0.83 (0.74-0.89; p<0.001) and 0.87 (0.79-0.93; p<0.001), respectively. CONCLUSIONS: The novel findings of our study were that serum caspase-3 levels during the first week of TBI were lower in survivors and could predict 30-day mortality.