Neurological Comorbidity Is a Predictor of Death in Covid-19 Disease: A Cohort Study on 576 Patients.

Introduction: Prognosis of Coronavirus disease 2019 (Covid-19) patients with vascular risk factors, and certain comorbidities is worse. The impact of chronic neurological disorders (CND) on prognosis is unclear. We evaluated if the presence of CND in Covid-19 patients is a predictor of a higher in-hospital mortality. As secondary endpoints, we analyzed the association between CND, Covid-19 severity, and laboratory abnormalities during admission. Methods: Retrospective cohort study that included all the consecutive hospitalized patients with confirmed Covid-19 disease from March 8th to April 11th, 2020. The study setting was Hospital Clínico, tertiary academic hospital from Valladolid. CND was defined as those neurological conditions causing permanent disability. We assessed demography, clinical variables, Covid-19 severity, laboratory parameters and outcome. The primary endpoint was in-hospital all-cause mortality, evaluated by multivariate cox-regression log rank test. We analyzed the association between CND, covid-19 severity and laboratory abnormalities. Results: We included 576 patients, 43.3% female, aged 67.2 years in mean. CND were present in 105 (18.3%) patients. Patients with CND were older, more disabled, had more vascular risk factors and comorbidities and fewer clinical symptoms of Covid-19. They presented 1.43 days earlier to the emergency department. Need of ventilation support was similar. Presence of CND was an independent predictor of death (HR 2.129, 95% CI: 1.382-3.280) but not a severer Covid-19 disease (OR: 1.75, 95% CI: 0.970-3.158). Frequency of laboratory abnormalities was similar, except for procalcitonin and INR. Conclusions: The presence of CND is an independent predictor of mortality in hospitalized Covid-19 patients. That was not explained neither by a worse immune response to Covid-19 nor by differences in the level of care received by patients with CND.

Author Correction: Combined quantification of procalcitonin and HLA-DR improves sepsis detection in surgical patients.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.

Cerebral Oxygen Saturation and Negative Postoperative Behavioral Changes in Pediatric Surgery: A Prospective Observational Study.

OBJECTIVE: To evaluate if an intraoperative cerebral regional oxygen saturation (crSO2) decrease, less pronounced than 20% below baseline (the current threshold believed to be associated with cognitive dysfunction in adults), is associated with negative postoperative behavioral changes (NPOBC) in the pediatric population after noncardiac surgeries. STUDY DESIGN: A prospective observational study was conducted with 198 children aged 2-12 years old scheduled for noncardiac procedures under general anesthesia. Intraoperatively, crSO2 was monitored with a cerebral oximeter. On postoperative day 7, the Post-Hospital Behavior Questionnaire was used to diagnose NPOBC. RESULTS: The incidence of NPOBC was 38.8%. Logistic regression analysis revealed that with every 1% reduction of crSO2 from the baseline value, the odds of developing NPOBC were 1.199 higher. Likewise, preoperative anxiety (OR 2.832, P = .006), duration of surgery (OR 1.026, P < .0001), and being between the ages of 2 and 3 years (OR 2.604, P = .048) were associated with NPOBC incidence. The multivariable logistic regression model receiver operating characteristic curve showed an area under the curve (95% CI) = 0.820 (0.759-0.881). CONCLUSIONS: During noncardiac surgeries in the pediatric population, an intraoperative decrease in crSO2 less pronounced than 20% from the baseline value is associated with negative postoperative behavior changes on postoperative day 7. The long-term implications remain to be determined, but this supports attention to crSO2 during noncardiac surgeries.

Quantification of Immune Dysregulation by Next-generation Polymerase Chain Reaction to Improve Sepsis Diagnosis in Surgical Patients.

OBJECTIVES: To quantify immunological dysfunction in surgical patients with presence/absence of sepsis using a droplet digital polymerase chain reaction (ddPCR) transcriptomic analysis. The study also aims to evaluate this approach for improving identification of sepsis in these patients. BACKGROUND: Immune dysregulation is a central event in sepsis. Quantification of the expression of immunological genes participating in the pathogenesis of sepsis could represent a new avenue to improve its diagnosis. METHODS: Expression of 6 neutrophil protease genes (MMP8, OLFM4, LCN2/NGAL, LTF, PRTN3, MPO) and also of 5 genes involved in the immunological synapse (HLA-DRA, CD40LG, CD3E, CD28, ICOS) was quantified in blood from 101 surgical patients with sepsis, 53 uninfected surgical patients, and 16 blood donors by using ddPCR. Areas under receiver operating characteristic curves (AUROC) and multivariate regression analysis were employed to test individual genes and gene ratios to identify sepsis, in comparison with procalcitonin. RESULTS: Sepsis-induced overexpression of neutrophil protease genes and depressed expression of immunological synapse genes. MMP8/HLA-DRA, LCN2/HLA-DRA outperformed procalcitonin in differentiating between patients with sepsis and surgical controls in the AUROC analysis: LCN2/HLA-DRA: 0.90 (0.85-0.96), MMP8/HLA-DRA: 0.89 (0.84-0.95), procalcitonin: 0.80 (0.73-0.88) (AUROC, confidence interval 95%), and also in the multivariate analysis: LCN2/HLA-DRA: 8.57 (2.25-32.62); MMP8/HLA-DRA: 8.03 (2.10-30.76), procalcitonin: 4.20 (1.15-15.43) [odds ratio (confidence interval 95%)]. Gene expression levels of HLA-DRA were an independent marker of hospital mortality. CONCLUSIONS: Quantifying the transcriptomic ratios MMP8/HLA-DRA, LCN2/HLA-DRA by ddPCR is a promising approach to improve sepsis diagnosis in surgical patients.

Combined quantification of procalcitonin and HLA-DR improves sepsis detection in surgical patients.

Early recognition of sepsis is a key factor to improve survival to this disease in surgical patients, since it allows prompt control of the infectious source. Combining pro-inflammatory and immunosupression biomarkers could represent a good strategy to improve sepsis detection. Here we evaluated the combination of procalcitonin (PCT) with gene expression levels of HLA-DRA to detect sepsis in a cohort of 154 surgical patients (101 with sepsis and 53 with no infection). HLA-DRA expression was quantified using droplet digital PCR, a next-generation PCR technology. Area under the receiver operating curve analysis (AUROC) showed that the PCT/HLA-DRA ratio outperformed PCT to detect sepsis (AUROC [CI95%], p): PCT: 0.80 [0.73-0.88], <0.001; PCT/HLA-DRA: 0.85 [0.78-0.91], <0.001. In the multivariate analysis, the ratio showed a superior ability to predict sepsis compared to that of PCT (OR [CI 95%], p): PCT/HLA-DRA: 7.66 [1.82-32.29], 0.006; PCT: 4.21 [1.15-15.43] 0.030. Multivariate analysis was confirmed using a new surgical cohort with 74 sepsis patients and 21 controls: PCT/HLA-DRA: 34.86 [1.22-995.08], 0.038; PCT: 5.52 [0.40-75.78], 0.201. In conclusion, the combination of PCT with HLA-DRA is a promising strategy for improving sepsis detection in surgical patients.

Defining immunological dysfunction in sepsis: A requisite tool for precision medicine.

OBJECTIVES: Immunological dysregulation is now recognised as a major pathogenic event in sepsis. Stimulation of immune response and immuno-modulation are emerging approaches for the treatment of this disease. Defining the underlying immunological alterations in sepsis is important for the design of future therapies with immuno-modulatory drugs. METHODS: Clinical studies evaluating the immunological response in adult patients with Sepsis and published in PubMed were reviewed to identify features of immunological dysfunction. For this study we used key words related with innate and adaptive immunity. RESULTS: Ten major features of immunological dysfunction (FID) were identified involving quantitative and qualitative alterations of [antigen presentation](FID1), [T and B lymphocytes] (FID2), [natural killer cells] (FID3), [relative increase in T regulatory cells] (FID4), [increased expression of PD-1 and PD-ligand1](FID5), [low levels of immunoglobulins](FID6), [low circulating counts of neutrophils and/or increased immature forms in non survivors](FID7), [hyper-cytokinemia] (FID8), [complement consumption] (FID9), [defective bacterial killing by neutrophil extracellular traps](FID10). CONCLUSIONS: This review article identified ten major features associated with immunosuppression and immunological dysregulation in sepsis. Assessment of these features could help in utilizing precision medicine for the treatment of sepsis with immuno-modulatory drugs.

The original sins of clinical trials with intravenous immunoglobulins in sepsis.

Intravenous immunoglobulins (IVIGs) have not yet demonstrated robust evidence in the benefit for treatment of sepsis. In spite of multiple clinical trials performed with IVIG in sepsis, it remains an experimental therapy for this severe condition. Nonetheless, these trials do not address a number of potential confounding factors, concerning both the patient and the IVIG preparations, which could greatly affect the final result. To name a few, endogenous levels of immunoglobulin isotypes and subclasses are not assessed prior to treatment. The presence/absence of patient antibodies against the microorganism(s) causing sepsis is not evaluated. The accuracy of antibiotic prescription is not included as an adjusting variable. The degree of patient immunosuppression (previous or induced by sepsis) is not documented. In turn, the concentration and antimicrobial specificities of the antibodies contained in the batches of IVIG are not assessed. Neither the pharmacokinetics of IVIG nor its potential immunomodulatory effects are evaluated. In addition, the concept of 'window of opportunity' for IVIG administration following diagnosis of sepsis is not considered. In conclusion, addressing these factors could help to individualise treatment with IVIG for sepsis, which could enhance the opportunities of this drug to show benefits in terms of survival in this severe condition.

Bugs, hosts and ICU environment: Countering pan-resistance in nosocomial microbiota and treating bacterial infections in the critical care setting / Gérmenes, huéspedes y el entorno de la Unidad de Cuidados Intensivos: contrarrestando la panresistencia en la microbiota nosocomial para tratar las infecciones bacterianas en cuidados críticos

ICUs are areas where resistance problems are the largest, and these constitute a major problem for the intensivist's clinical practice. Main resistance phenotypes among nosocomial microbiota are (I) vancomycin-resistance/heteroresistance and tolerance in grampositives (MRSA, enterococci) and (II) efflux pumps/enzymatic resistance mechanisms (ESBLs, AmpC, metallo-betalactamases) in gramnegatives. These phenotypes are found at different rates in pathogens causing respiratory (nosocomial pneumonia/ventilator-associated pneumonia), bloodstream (primary bacteremia/catheter-associated bacteremia), urinary, intraabdominal and surgical wound infections and endocarditis in the ICU. New antibiotics are available to overcome non-susceptibility in grampositives; however, accumulation of resistance traits in gramnegatives has led to multidrug resistance, a worrisome problem nowadays. This article reviews microorganism/infection risk factors for multidrug resistance, suggesting adequate empirical treatments. Drugs, patient and environmental factors all play a role in the decision to prescribe/recommend antibiotic regimens in the specific ICU patient, implying that intensivists should be familiar with available drugs, environmental epidemiology and patient factors (AU)

UCIs son las áreas donde los problemas de resistencia son los más grandes, y éstos constituyen un problema importante para la práctica clínica de los intensivistas . Fenotipos de resistencia principales entre la microbiota nosocomial son ( I ) vancomycin-resistance/heteroresistance y tolerancia en grampositives ( MRSA, enterococos ) y ( II ) las bombas de flujo / mecanismos enzimáticos de resistencia ( BLEE , AmpC , metalo- betalactamasas ) en gramnegativos . Estos fenotipos se encuentran en diferentes tipos de patógenos causantes de las vías respiratorias (neumonía / pulmonía nosocomial asociada a ventilación mecánica), el torrente sanguíneo ( bacteremia primaria / bacteriemia asociada a catéter ) , urinario, infecciones de las heridas quirúrgicas intraabdominales y endocarditis y en la UCI. Nuevos antibióticos están disponibles para superar la no - susceptibilidad in grampositives, sin embargo, la acumulación de rasgos de resistencia en gramnegativos ha dado lugar a la resistencia a múltiples fármacos, un problema preocupante en la actualidad. Este artículo revisa los factores de riesgo microorganismo / infección de la resistencia a múltiples fármacos, lo que sugiere tratamientos empíricos adecuados. Las drogas, el paciente y los factores ambientales juegan un papel en la decisión de prescribir / recomendar regímenes de antibióticos en el paciente en la UCI específica, lo que implica que los intensivistas deben familiarizarse con los fármacos disponibles, epidemiología ambiental y los factores del paciente (AU)

Bugs, hosts and ICU environment: countering pan-resistance in nosocomial microbiota and treating bacterial infections in the critical care setting.

ICUs are areas where resistance problems are the largest, and these constitute a major problem for the intensivist's clinical practice. Main resistance phenotypes among nosocomial microbiota are (i) vancomycin-resistance/heteroresistance and tolerance in grampositives (MRSA, enterococci) and (ii) efflux pumps/enzymatic resistance mechanisms (ESBLs, AmpC, metallo-betalactamases) in gramnegatives. These phenotypes are found at different rates in pathogens causing respiratory (nosocomial pneumonia/ventilator-associated pneumonia), bloodstream (primary bacteremia/catheter-associated bacteremia), urinary, intraabdominal and surgical wound infections and endocarditis in the ICU. New antibiotics are available to overcome non-susceptibility in grampositives; however, accumulation of resistance traits in gramnegatives has led to multidrug resistance, a worrisome problem nowadays. This article reviews microorganism/infection risk factors for multidrug resistance, suggesting adequate empirical treatments. Drugs, patient and environmental factors all play a role in the decision to prescribe/recommend antibiotic regimens in the specific ICU patient, implying that intensivists should be familiar with available drugs, environmental epidemiology and patient factors.

Bugs, hosts and ICU environment: countering pan-resistance in nosocomial microbiota and treating bacterial infections in the critical care setting.

ICUs are areas where resistance problems are the largest, and they constitutes a major problem for the intensivist's clinical practice. Main resistance phenotypes among nosocomial microbiota are: i) vancomycin-resistance/heteroresistance and tolerance in grampositives (MRSA, enterococci) and ii) efflux pumps/enzymatic resistance mechanisms (ESBLs, AmpC, metallobetalactamases) in gramnegatives. These phenotypes are found at different rates in pathogens causing respiratory (nosocomial pneumonia/ventilator-associated pneumonia), bloodstream (primary bacteremia/catheter-associated bacteremia), urinary, intraabdominal and surgical wound infections and endocarditis in the ICU. New antibiotics are available to overcome non-susceptibility in grampositives; however, accumulation of resistance traits in gramnegatives has lead to multidrug resistance, a worrisome problem nowadays. This article reviews by microorganism/infection risk factors for multidrug resistance, suggesting adequate empirical treatments. Drugs, patient and environmental factors all play a role in the decision to prescribe/recommend antibiotic regimens in the specific ICU patient, implying that intensivists should be familiar with available drugs, environmental epidemiology and patient factors.

Intraoperative PaO2 is not related to the development of surgical site infections after major cardiac surgery.

BACKGROUND: The perioperative use of high inspired oxygen fraction (FIO2) for preventing surgical site infections (SSIs) has demonstrated a reduction in their incidence in some types of surgery however there exist some discrepancies in this respect. The aim of this study was to analyze the relationship between PaO2 values and SSIs in cardiac patients. METHODS: We designed a prospective study in which 1,024 patients undergoing cardiac surgery were analyzed. RESULTS: SSIs were observed in 5.3% of patients. There was not significant difference in mortality at 30 days between patients with and without SSIs. In the uni and multivariate analysis no differences in function of the inspired oxygen fraction administrated were observed. CONCLUSIONS: We observed that the PaO2 in adult cardiac surgery patients was not related to SSI rate.

Prevalencia de prick-test positivo a látex en pacientes sometidos a intervención quirúrgica / Prevalence of positive prick-test to latex in the surgical population

No disponible

No disponible

¿Se utiliza adecuadamente la vancomicina en la práctica clínica? / Does vancomicine have an adecuate use in clinical practice?

No disponible