Impact of Vancomycin trough levels monitoring on uncomplicated methilcillin-resistant Staphylococcus aureus bacteremia in chronic kidney disease on hemodialysis, retrospective cohort.

BACKGROUND: CKD patients on hemodialysis (HD) with Staphylococcus aureus (SA) bacteremia present high morbidity, mortality and increased risk of MRSA. Vancomycin is the antibiotic of choice in these cases, it has a narrow therapeutic margin and inadequate dosage generates a risk of toxicity, therefore, the recommendation is to dosage it through serum levels. METHODS: This is a retrospective cohort study in 3 hospitals of third level of complexity in the city of Medellin in which there were differences in the measurement and implementation of vancomycin25 dosage based on trough levels (VL) in patients with chronic kidney disease on hemodialysis (CKD- HD) with uncomplicated bacteremia based infection by methilcillin-resistant Staphyloccocus aureus (MRSA). The primary outcome was the composite of hospital mortality, clinical response (fever, hemodynamic instability and altered consciousness), complications associated with bacteremia, or bacteriological response failure (positive cultures at first week follow-up) at 7 days. The composite variables were analyzed individually as secondary outcomes. RESULTS: The main unadjusted outcome (OR 1.3, CI 0.6 - 2.7) and adjusted for age, Charlson index, loading dose, initial dose, dosing frequency and MIC to vancomycin (OR 1.2, CI 0.5 - 2.7). Regarding adjusted secondary outcomes: clinical response (OR 1.4 CI 0.3 - 5.8), death (OR 1.3 CI 0.3 - 4.6) and complications (OR 0.9, CI 0.37 - 2.2). CONCLUSIONS: We conclude that the measurement of trough levels in patients with HD-CKD does not modify the composite outcome. The main limitation is the sample size and type of study, randomized control trials may be required to confirm the results presented.

Cross-Cultural Validation of the TeamSTEPPS Teamwork Perceptions Questionnaire-Spanish in Colombia.

BACKGROUND: Teamwork influences health care quality and patient safety. Yet, validated instruments for assessing teamwork in Colombia are lacking. PURPOSE: The purpose of this study was to validate the Spanish version of the TeamSTEPPS-Teamwork Perceptions Questionnaire (T-TPQ-S) for the Colombian health care context. METHODS: The T-TPQ-S underwent translation, cultural adaptation, and comprehensive psychometric testing, including reliability and confirmatory factor analyses and item difficulty and discrimination analyses. RESULTS: The T-TPQ-S demonstrated high internal consistency and excellent fit to the theoretical model. Item discrimination was within expected ranges, with response thresholds displaying an ascending order. The tool better differentiated subjects with low and high teamwork perceptions. CONCLUSIONS: The T-TPQ-S is an effective, reliable, and valid instrument for assessing teamwork perception among Colombian health care workers.

Predictive Factors of Hospital-Acquired Bacterial Infections in Patients With Systemic Lupus Erythematosus.

OBJECTIVE: We aimed to identify the predictive factors of hospital-acquired bacterial infections in patients with systemic lupus erythematosus (SLE). METHODS: This chart review study included patients with SLE who were hospitalized between 2009 and 2020 for reasons other than infection. The outcome was defined as any infection confirmed using any bacterial isolation method or diagnosed by treating physicians and required treatment with intravenous antibiotics. For statistical analysis, logistic regression analyses were performed. RESULTS: In total, 1678 patients (87.6% women) were included. The median age was 33 years (interquartile range, 24-47 years). The incidence of hospital-acquired infections was 13.9% (233 infections). Age, Systemic Lupus Erythematosus Disease Activity Index score, Systemic Lupus International Collaborating Clinics damage score, blood urea nitrogen and C-reactive protein levels, dosage of steroid in the previous month, recent use of 1 or more immunosuppressants, admission with a central venous catheter (or dialysis catheter), and use of central venous catheter or bladder catheter in the first 5 days were the predictive factors of nosocomial infections. CONCLUSION: The patients' infection risk profile should be assessed to accurately determine the risk-benefit balance of any therapeutic intervention, minimize exposure to steroids and immunosuppressants, and maintain a low threshold for the early diagnosis of infections. Further studies should assess whether the modification of some identified factors could reduce the incidence of nosocomial infections.

Improving the diagnosis and prognosis of sepsis according to the sources of infection.

INTRODUCTION: The clinical presentation of sepsis is heterogeneous and largely depends on the primary site of infection. Currently, factors associated with sepsis outcomes do not differentiate between infection sites. The objective of this investigation was to identify variables associated with risk of in-hospital mortality or intensive care unit (ICU) admission, according to infection sites. METHODS: This was a secondary analysis of a multicentre prospective cohort of ED patients ≥18 years old from three university hospitals in Medellín, Colombia. Multivariable logistic regression models were performed to estimate the association of factors with in-hospital mortality or ICU admission according to five infection sites: urinary tract infection (UTI), community-acquired pneumonia (CAP), intra-abdominal infection, sepsis without evident source (primary) and other sites. RESULTS: The infection sites of the 1947 patients included were: UTI (n=586), CAP (n=585), intra-abdominal infection (n=213), primary (n=224) and other sites (n=339). In the multivariable model, the factors associated with in-hospital mortality or ICU admission varied by infection site: respiratory rate (RR), systolic blood pressure (SBP) and lactate for UTI; heart rate (HR), RR and temperature <38°C for CAP; Glasgow Coma Scale (GCS), lactate and age <65 for intra-abdominal infection; SBP, GCS, lactate and temperature <38°C for primary and RR, GCS and temperature <38°C for other. CONCLUSIONS: Our results suggest that the diagnosis and prognosis of sepsis in emergency care should consider different clinical criteria, based on site of infection. Given the heterogeneity and interindividual variability of sepsis, a more individualised approach could help to direct treatment, monitor response and facilitate initial clinical decisions.

Validation of VIRSTA and Predicting Risk of Endocarditis Using a Clinical Tool (PREDICT) Scores to Determine the Priority of Echocardiography in Patients With Staphylococcus aureus Bacteremia.

BACKGROUND: Infective endocarditis (IE) secondary to Staphylococcus aureus bacteremia (SAB) has high morbidity and mortality. The systematic use of echocardiography in SAB is controversial. We aimed to validate VIRSTA and Predicting Risk of Endocarditis Using a Clinical Tool (PREDICT) scores for predicting the risk of IE in Colombian patients with SAB and, consequently, to determine the need for echocardiography. METHODS: Cohort of patients hospitalized with SAB in 2 high complexity institutions in Medellin, Colombia, between 2012 and 2018. The diagnosis of IE was established based on the modified Duke criteria. The VIRSTA and PREDICT scores were calculated from the clinical records, and their operational performance was calculated. RESULTS: The final analysis included 922 patients, 62 (6.7%) of whom were diagnosed with IE. The frequency of IE in patients with a negative VIRSTA scale was 0.44% (2/454). The frequency of IE in patients with a negative PREDICT scale on day 5 was 4.8% (30/622). The sensitivity and negative predictive value (NPV) of the VIRSTA scale was 96.7% and 99.5%, respectively. For the PREDICT scale on day 5, the sensitivity and NPV were 51.6% and 95.1%, respectively. The discrimination, given by the area under the receiver operating characteristic curve, was 0.86 for VIRSTA and 0.64 for PREDICT. CONCLUSIONS: In patients with negative VIRSTA, screening echocardiography may be unnecessary because of the low frequency of IE. In PREDICT-negative patients, despite the low frequency of IE, it is not safe to omit echocardiography.

Predictive models of infection in patients with systemic lupus erythematosus: A systematic literature review.

INTRODUCTION: Having reliable predictive models of prognosis/the risk of infection in systemic lupus erythematosus (SLE) patients would allow this problem to be addressed on an individual basis to study and implement possible preventive or therapeutic interventions. OBJECTIVE: To identify and analyze all predictive models of prognosis/the risk of infection in patients with SLE that exist in medical literature. METHODS: A structured search in PubMed, Embase, and LILACS databases was carried out until May 9, 2020. In addition, a search for abstracts in the American Congress of Rheumatology (ACR) and European League Against Rheumatism (EULAR) annual meetings' archives published over the past eight years was also conducted. Studies on developing, validating or updating predictive prognostic models carried out in patients with SLE, in which the outcome to be predicted is some type of infection, that were generated in any clinical context and with any time horizon were included. There were no restrictions on language, date, or status of the publication. To carry out the systematic review, the CHARMS (Critical Appraisal and Data Extraction for Systematic Reviews of Prediction Modelling Studies) guideline recommendations were followed. The PROBAST tool (A Tool to Assess the Risk of Bias and Applicability of Prediction Model Studies) was used to assess the risk of bias and the applicability of each model. RESULTS: We identified four models of infection prognosis in patients with SLE. Mostly, there were very few events per candidate predictor. In addition, to construct the models, an initial selection was made based on univariate analyses with no contraction of the estimated coefficients being carried out. This suggests that the proposed models have a high probability of overfitting and being optimistic. CONCLUSIONS: To date, very few prognostic models have been published on the infection of SLE patients. These models are very heterogeneous and are rated as having a high risk of bias and methodological weaknesses. Despite the widespread recognition of the frequency and severity of infections in SLE patients, there is no reliable predictive prognostic model that facilitates the study and implementation of personalized preventive or therapeutic measures.Protocol registration number: PROSPERO CRD42020171638.

Supervised classification techniques for prediction of mortality in adult patients with sepsis.

BACKGROUND: Sepsis mortality is still unacceptably high and an appropriate prognostic tool may increase the accuracy for clinical decisions. OBJECTIVE: To evaluate several supervised techniques of Artificial Intelligence (AI) for classification and prediction of mortality, in adult patients hospitalized by emergency services with sepsis diagnosis. METHODS: Secondary data analysis of a prospective cohort in three university hospitals in Medellín, Colombia. We included patients >18 years hospitalized for suspected or confirmed infection and any organ dysfunction according to the Sepsis-related Organ Failure Assessment. The outcome variable was hospital mortality and the prediction variables were grouped into those related to the initial clinical treatment and care or to the direct measurement of physiological disturbances. Four supervised classification techniques were analyzed: the C4.5 Decision Tree, Random Forest, artificial neural networks (ANN) and support vector machine (SVM) models. Their performance was evaluated by the concordance between the observed and predicted outcomes and by the discrimination according to AUC-ROC. RESULTS: A total of 2510 patients with a median age of 62 years (IQR = 46-74) and an overall hospital mortality rate of 11.5% (n = 289). The best discrimination was provided by the SVM and ANN using physiological variables, with an AUC-ROC of 0.69 (95%CI: 0.62; 0.76) and AUC-ROC of 0.69 (95%CI: 0.61; 0.76) respectively. CONCLUSION: Deep learning and AI are increasingly used as support tools in clinical medicine. Their performance in a syndrome as complex and heterogeneous as sepsis may be a new horizon in clinical research. SVM and ANN seem promising for improving sepsis classification and prognosis.

Biomarkers as a Prognostic Factor in COPD Exacerbation: A Cohort Study.

The acute exacerbations of COPD (AECOPD) are one of the main causes of hospitalization and morbimortality in the adult population. There are not many tools available to predict the clinical course of these patients during exacerbations. Our goal was to estimate the clinical utility of C Reactive Protein (CRP), Mean Platelet Volume (MPV), eosinophil count and neutrophil/lymphocyte ratio (NLR) as in-hospital prognostic factors in patients with AECOPD. A prospective cohort study was conducted in patients who consulted three reference hospitals in the city of Medellín for AECOPD and who required hospitalization between 2017 and 2020. A multivariate analysis was performed to estimate the effect of biomarkers in the two primary outcomes: the composite outcome of in-hospital death and/or admission to the ICU and hospital length-of-stay. A total of 610 patients with a median age of 74 years were included; 15% were admitted to the ICU and 3.9% died in the hospital. In the multivariate analysis adjusted for confounding variables, the only marker significantly associated with the risk of dying or being admitted to the ICU was the NLR > 5 (OR: 3; CI95%: 1.5; 6). Similarly, the NLR > 5 was also associated to a lower probability of being discharged alive from the institution (SHR: 0.73; CI95%: 0.57; 0.94) and, therefore, a longer hospital stay. It was found that a neutrophil/lymphocyte ratio greater than 5 is a strong predictor of mortality or ICU admissions and a longer hospital stay in patients hospitalized with AECOPD.

Positive Culture and Prognosis in Patients With Sepsis: A Prospective Cohort Study.

PURPOSE: To analyze the prognostic role of positive cultures in patients with sepsis. METHODS: A prospective cohort study in a tertiary referral hospital in Medellín, Colombia. Adults older than 18 years of age with a bacterial infection diagnosis according to Centers for Disease Control criteria and sepsis (evidence of organ dysfunction) were included. A logistic regression model was used to determine the association between positive cultures and hospital mortality, and a Cox regression with a competing risk modeling approach was used to determine the association between positive cultures and hospital stay as well as secondary infections. RESULTS: Overall, 408 patients had positive cultures, of which 257 were blood culture, and 153 had negative cultures. Patients with positive cultures had a lower risk of mortality (odds ratio [OR], 0.43; 95% confidence interval [CI], 0.27-0.68), but this association was not maintained after adjusting for confounding factors (OR, 0.56; 95% CI, 0.31-1.01). No association was found with the hospital stay (adjusted subhazard ratio [SHR], 1.06; 95% CI, 0.83-1.35). There was no association between positive cultures and the presence of secondary infections (adjusted SHR, 0.99; 95% CI, 0.58-1.71). CONCLUSION: Positive cultures are not associated with prognosis in patients with sepsis.

Antimicrobial agent prescription: a prospective cohort study in patients with sepsis and septic shock.

OBJECTIVE: To assess the true association between appropriate prescription of antibiotics and prognosis in patients with sepsis, a key issue in health care and quality improvement strategies. METHODS: Prospective cohort study in three university hospitals to determine whether the empirical prescription of antibiotics was adequate or inadequate, and to compare hospital death rates and length of stay according to different classifications of antibiotics prescription. Logistic regression models for risk estimation were fitted. RESULTS: A total of 705 patients with severe sepsis were included. No differences were found in positive-culture patients (n = 545) regarding the risk of death with insufficient spectrum antibiotics, compared to patients who received adequate spectrum antibiotics (OR = 0.90; 95% CI = 0.55-1.48). Delay in initiating antibiotics was not associated with the risk of death in patients with adequate spectrum of antibiotics, either with positive (OR = 1.04; 95% CI = 0.99-1.08) or negative cultures (OR = 0.98; 95% CI = 0.92-1.04). There were no differences in the length of hospital stay, according to the antibiotic prescription (median 11 days, IQR = 7-18 days for the whole cohort). CONCLUSIONS: No associations were found between inadequate antibiotic prescription or delay to initiate therapy and mortality or length of stay.

Organ Dysfunction in Sepsis: An Ominous Trajectory From Infection To Death.

Sepsis is a highly complex and lethal syndrome with highly heterogeneous clinical manifestations that makes it difficult to detect and treat. It is also one of the major and most urgent global public health challenges. More than 30 million people are diagnosed with sepsis each year, with 5 million attributable deaths and long-term sequalae among survivors. The current international consensus defines sepsis as a life-threatening organ dysfunction caused by a dysregulated host response to an infection. Over the past decades substantial research has increased the understanding of its pathophysiology. The immune response induces a severe macro and microcirculatory dysfunction that leads to a profound global hypoperfusion, injuring multiple organs. Consequently, patients with sepsis might present dysfunction of virtually any system, regardless of the site of infection. The organs more frequently affected are kidneys, liver, lungs, heart, central nervous system, and hematologic system. This multiple organ failure is the hallmark of sepsis and determines patients' course from infection to recovery or death. There are tools to assess the severity of the disease that can also help to guide treatment, like the Sequential Organ Failure Assessment (SOFA) score. However, sepsis disease process is vastly heterogeneous, which could explain why interventions targeted to directly intervene its mechanisms have shown unsuccessful results and predicting outcomes with accuracy is still elusive. Thus, it is required to implement strong public health strategies and leverage novel technologies in research to improve outcomes and mitigate the burden of sepsis and septic shock worldwide.

Attenuation of the physiological response to infection on adults over 65 years old admitted to the emergency room (ER).

It has been considered that the elderly have clinical manifestations different from the ones observed in middle-age adults during an injury event. This hypothesis has not been extensively explored in sepsis and bacterial infections. Secondary analysis of two prospective studies including 2611 patients over 18 years of age admitted to the emergency room with confirmed or probable bacterial infections and sepsis. The outcome measures were heart rate, respiratory rate, systolic blood pressure, temperature, Glasgow Coma Scale, creatinine, PaO2/FiO2 and platelets daily during the first week. Compared to survivors younger than 65, the deceased under 65 had an average heart rate of 12.5 beats per minute per day higher (95% CI 9.32; 15.61), while patients over 65 who died barely had an average 5.7 beats per minute per day higher than the same reference group (95% CI 3.45; 8.06). The systolic blood pressure had a significant decreased in those who died younger than 65, compared to survivors with the same age, in both cohorts (-5.2 mmHg, 95% CI -8.17; -2.23 and -8.5 mmHg, 95% CI -13.48; -3.54, respectively), while those older than 65 who died had a nonsignificant increase (+1.6 mmHg, 95% CI -1.33; 4.62 and +0.1, 95% CI -6.48; 6.72, respectively) compared to the same reference group. The behavior of most clinical and laboratory variables suggests a less pronounced response of subjects above 65 years of age who died 28 days after being diagnosed with sepsis.

Validation of trauma scales: ISS, NISS, RTS and TRISS for predicting mortality in a Colombian population.

BACKGROUND: Our purpose was to validate the performance of the ISS, NISS, RTS and TRISS scales as predictors of mortality in a population of trauma patients in a Latin American setting. MATERIALS AND METHODS: Subjects older than 15 years with diagnosis of trauma, lesions in two or more body areas according to the AIS and whose initial attention was at the hospital in the first 24 h were included. The main outcome was inpatient mortality. Secondary outcomes were admission to the intensive care unit, requirement of mechanical ventilation and length of stay. A logistic regression model for hospital mortality was fitted with each of the scales as an independent variable, and its predictive accuracy was evaluated through discrimination and calibration statistics. RESULTS: Between January 2007 and July 2015, 4085 subjects were enrolled in the study. 84.2% (n = 3442) were male, the mean age was 36 years (SD = 16), and the most common trauma mechanism was blunt type (80.1%; n = 3273). The medians of ISS, NISS, TRISS and RTS were: 14 (IQR = 10-21), 17 (IQR = 11-27), 4.21 (IQR = 2.95-5.05) and 7.84 (IQR = 6.90-7.84), respectively. Mortality was 9.3%, and the discrimination for ISS, NISS, TRISS and RTS was: AUC 0.85, 0.89, 0.86 and 0.92, respectively. No one scale had appropriate calibration. CONCLUSION: Determining the severity of trauma is an essential tool to guide treatment and establish the necessary resources for attention. In a Colombian population from a capital city, trauma scales have adequate performance for the prediction of mortality in patients with trauma.

Immunological characterization of compensatory anti-inflammatory response syndrome in patients with severe sepsis: a longitudinal study*.

OBJECTIVES: To perform a complete immunological characterization of compensatory anti-inflammatory response syndrome in patients with sepsis and to explore the relationship between these changes and clinical outcomes of 28-day mortality and secondary infections. DESIGN: Prospective single-center study conducted between April 2011 and December 2012. SETTING: ICUs from Hospital Universitario San Vicente Fundación at Medellin, Colombia. PATIENTS: One hundred forty-eight patients with severe sepsis. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: At days 0, 1, 3, 5, 10, and 28, we determined the expression of HLA-DR in monocytes and the apoptosis and the proliferation index in T lymphocytes, as well as the levels of tumor necrosis factor-α, interleukin-6, interleukin-1ß, interleukin-10, and transforming growth factor-ß in both plasma and cell culture supernatants of peripheral blood mononuclear cells. The mean percentage of HLA-DR was 60.7 at enrollment and increased by 0.9% (95% CI, 0.7-1.2%) per day. The mean percentage of CD4 T cells and CD8 T cells AV+/7-AAD- at enrollment was 37.2% and 20.4%, respectively, but it diminished at a rate of -0.5% (95% CI, -0.7% to -0.3%) and -0.3% (95% CI, -0.4% to -0.2%) per day, respectively. Plasma levels of interleukin-6 and interleukin-10 were 290 and 166 pg/mL and decreased at a rate of -7.8 pg/mL (95% CI, -9.5 to -6.1 pg/mL) and -4 pg/mL (95% CI, -5.1 to -2.8 pg/mL) per day, respectively. After controlling for confounders, only sustained plasma levels of interleukin-6 increase the risk of death (hazard ratio 1.003; 95% CI, 1.001-1.006). CONCLUSIONS: We found no evidence to support a two-phase model of sepsis pathophysiology. However, immunological variables did behave in a mixed and time-dependent manner. Further studies should evaluate changes over time of interleukin-6 plasma levels as a prognostic biomarker for critically ill patients.

[Implementation of the strategy "Clean Care is Safer Care" in a third level hospital in Medellín, Colombia]. / Implementación de la estrategia "Atención Limpia es Atención Segura" en un hospital de tercer nivel en Medellín, Colombia.

INTRODUCTION: Hand hygiene is the most cost-effective and simple measure of preventing healthcare associated infections (HAI). The approach to improve low compliance must be through multimodal interventions such as the "Clean Care is Safer Care" strategy (WHO). AIM: To estimate the efficacy of a multimodal strategy in improving hand hygiene in five wards of a tertiary care hospital in Medellín, Colombia (2008-2010). METHODS: Quasi-experimental before-after study. RESULTS: Hand hygiene compliance significantly increased after the intervention (82 to 89%, p = 0.007). The knowledge score increased from a median of 26 (IQR=22-28) to 30 (IQR=26-32, p = 0.001). Alcohol-based hand rub consumption increased significantly from 10.5 liters to 58.1 liters per 1000 patient-days [incidence ratio (IR) = 2.39, 95% CI = 1.99; 2.88]. Monthly HAI rates showed no significant variations during the same period [IR = 0.90, 95% CI = 0.71; 1.13]. DISCUSSION: This and other recent studies demonstrate that implementing a multimodal strategy for hand hygiene significantly increases compliance with this measure, irrespective of type of health worker or hospital department. CONCLUSIONS: Implementing a multimodal strategy we achieved significant increases in hand hygiene compliance but mild or no significant variations in monthly HAI rates.

Risk calculator of the clinical response to antihistamines in chronic urticaria: Development and internal validation.

Early detection of CSU patients with low probability of a clinical response with antihistamines could undergo prompt initiation of therapeutic alternatives. The aim of the study was to develop and internally validate a model for predicting the clinical response to antihistamines in adult patients with chronic spontaneous urticaria (CSU), who consult allergology and dermatology care centers. A cohort of CSU patients, recruited from four participating centers, were followed up for 12 months. Fifteen candidate variables were selected to be included in the multivariate model and then internal validation was done with bootstrap analysis with 1000 simulations. The outcome variable, clinical response to antihistamines, was evaluated with the UAS (Urticaria Activity Score) scale for seven days: "No response to antihistamines" was defined as UAS7 ≥7 points after at least one month with a maximum dose of antihistamines, while "Response to antiH1" was defined as UAS7 ≤6 points for at least three months with the use of antiH1. A total of 790 patients were included. Among the different models analyzed, the model that included age, angioedema, anxiety/depression, time with the disease, NSAIDs (Non-steroidal anti-inflammatory drugs) intolerance, and UAS7 baseline was considered the one with the best performance (accuracy 0.675, HL 0.87, AUC 0.727). The internal validation analyses demonstrated good consistency of the model. In conclusion, this prediction model identifies the probability of response to antihistamines in patients with chronic spontaneous urticaria. The model could be useful for a personalized therapeutic approach according to individual patient risk.

External validation of two clinical prediction models for mortality in COVID-19 patients (4C and NEWS2), in three centers in Medellín, Colombia: Assessing the impact of vaccination over time.

OBJECTIVES: External validation of the 4C and NEWS2 scores for the prediction of in-hospital mortality in COVID-19 patients, and evaluation of its operational performance in two time periods: before and after the start of the vaccination program in Colombia. METHODS: Retrospective cohort in three high complexity hospitals in the city of Medellín, Colombia, between June 2020 and April 2022. RESULTS: The areas under the ROC curve (AUC) for the 4C mortality risk score and the NEWS2 were 0.75 (95% CI 0.73-0.78) and 0.68 (95% CI 0.66-0.71), respectively. For the 4C score, the AUC for the first and second periods was 0.77 (95% CI 0.74-0.80) and 0.75 (95% CI 0.71-0.78); whilst for the NEWS2 score, it was 0.68 (95% CI 0.65-0.71) and 0.69 (95% CI 0.64-0.73). The calibration for both scores was adequate, albeit with reduced performance during the second period. CONCLUSIONS: The 4C mortality risk score proved to be the more adequate predictor of in-hospital mortality in COVID-19 patients in this Latin American population. The operational performance during both time periods remained similar, which shows its utility notwithstanding major changes, including vaccination, as the pandemic evolved.

Clinical course of sepsis, severe sepsis, and septic shock in a cohort of infected patients from ten Colombian hospitals.

BACKGROUND: Sepsis has several clinical stages, and mortality rates are different for each stage. Our goal was to establish the evolution and the determinants of the progression of clinical stages, from infection to septic shock, over the first week, as well as their relationship to 7-day and 28-day mortality. METHODS: This is a secondary analysis of a multicenter cohort of inpatients hospitalized in general wards or intensive care units (ICUs). The general estimating equations (GEE) model was used to estimate the risk of progression and the determinants of stages of infection over the first week. Cox regression with time-dependent covariates and fixed covariates was used to determine the factors related with 7-day and 28-day mortality, respectively. RESULTS: In 2681 patients we show that progression to severe sepsis and septic shock increases with intraabdominal and respiratory sources of infection [OR = 1,32; 95%IC = 1,20-1,46 and OR = 1.21, 95%CI = 1,11-1,33 respectively], as well as according to Acute Physiology and Chronic Health Evaluation II (APACHE II) [OR = 1,03; 95%CI = 1,02-1,03] and Sequential Organ Failure Assessment (SOFA) [OR = 1,16; 95%CI = 1,14-1,17] scores. The variables related with first-week mortality were progression to severe sepsis [HR = 2,13; 95%CI = 1,13-4,03] and septic shock [HR = 3,00; 95%CI = 1,50-5.98], respiratory source of infection [HR = 1,76; 95%IC = 1,12-2,77], APACHE II [HR = 1,07; 95% CI = 1,04-1,10] and SOFA [HR = 1,09; 95%IC = 1,04-1,15] scores. CONCLUSIONS: Intraabdominal and respiratory sources of infection, independently of SOFA and APACHE II scores, increase the risk of clinical progression to more severe stages of sepsis; and these factors, together with progression of the infection itself, are the main determinants of 7-day and 28-day mortality.

In vivo effect of statins on the expression of the HIV co-receptors CCR5 and CXCR4.

BACKGROUND: During the HIV-1 replication cycle, several molecules including chemokine receptors and cholesterol are crucial, and are therefore potential targets for therapeutic intervention. Indeed statins, compounds that inhibit cellular synthesis of cholesterol and have anti-inflammatory and immunomodulatory properties were shown to inhibit HIV-1 infection by R5 tropic strains but not by X4 strains in vitro, mainly by altering the chemokine receptor/ligands axes. Therefore, the objective of this study was to characterize in vivo, the capacity of statins to modulate in HIV seronegative and chronically HIV-1-infected adults the expression of CCR5 and CXCR4, of their ligands and the tropism of circulating HIV-1 strains. METHODS: Samples from asymptomatic HIV-1-infected adults enrolled in a clinical trial aimed at evaluating the antiretroviral activity of lovastatin were used to evaluate in vivo the modulation by lovastatin of CCR5, CXCR4, their ligands, and the shift in plasma viral tropism over one year of intervention. In addition, ten HIV negative adults received a daily oral dose of 40 mg of lovastatin or 20 mg of atorvastatin; seven other HIV negative individuals who received no treatment were followed as controls. The frequency and phenotype of immune cells were determined by flow-cytometry; mRNA levels of chemokine receptors and their ligands were determined by real-time PCR. Viral tropism was determined by PCR and sequencing, applying the clonal and clinical model of analyses. RESULTS: Our study shows that long-term administration of lovastatin in HIV-infected individuals does not induce a shift in viral tropism, or induce a significant modulation of CCR5 and CXCR4 on immune cells in HIV-infected patients. Similar results were found in HIV seronegative control subjects, treated with lovastatin or atorvastatin, but a significant increase in CCL3 and CCL4 transcription was observed in these individuals. CONCLUSIONS: These findings suggest that long-term administration of statins at therapeutic doses, does not significantly affect the expression of HIV-1 co-receptors or of their ligands. In addition it is important to point out that based on the results obtained, therapeutic administration of statins in HIV-infected patients with lipid disorders is safe in terms of selecting X4 strains.