Intubation Decision Based on Illness Severity and Mortality in COVID-19: An International Study.

OBJECTIVES: To evaluate the impact of intubation timing, guided by severity criteria, on mortality in critically ill COVID-19 patients, amidst existing uncertainties regarding optimal intubation practices. DESIGN: Prospective, multicenter, observational study conducted from February 1, 2020, to November 1, 2022. SETTING: Ten academic institutions in the United States and Europe. PATIENTS: Adults (≥ 18 yr old) confirmed with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and hospitalized specifically for COVID-19, requiring intubation postadmission. Exclusion criteria included patients hospitalized for non-COVID-19 reasons despite a positive SARS-CoV-2 test. INTERVENTIONS: Early invasive mechanical ventilation (EIMV) was defined as intubation in patients with less severe organ dysfunction (Sequential Organ Failure Assessment [SOFA] < 7 or Pao2/Fio2 ratio > 250), whereas late invasive mechanical ventilation (LIMV) was defined as intubation in patients with SOFA greater than or equal to 7 and Pao2/Fio2 ratio less than or equal to 250. MEASUREMENTS AND MAIN RESULTS: The primary outcome was mortality within 30 days of hospital admission. Among 4464 patients, 854 (19.1%) required mechanical ventilation (mean age 60 yr, 61.7% male, 19.3% Black). Of those, 621 (72.7%) were categorized in the EIMV group and 233 (27.3%) in the LIMV group. Death within 30 days after admission occurred in 278 patients (42.2%) in the EIMV and 88 patients (46.6%) in the LIMV group (p = 0.28). An inverse probability-of-treatment weighting analysis revealed a statistically significant association with mortality, with patients in the EIMV group being 32% less likely to die either within 30 days of admission (adjusted hazard ratio [HR] 0.68; 95% CI, 0.52-0.90; p = 0.008) or within 30 days after intubation irrespective of its timing from admission (adjusted HR 0.70; 95% CI, 0.51-0.90; p = 0.006). CONCLUSIONS: In severe COVID-19 cases, an early intubation strategy, guided by specific severity criteria, is associated with a reduced risk of death. These findings underscore the importance of timely intervention based on objective severity assessments.

Very-Low-Level Viremia, Inflammatory Biomarkers, and Associated Baseline Variables: Three-Year Results of the Randomized TANGO Study.

Background: We compared proportions of participants with target detected, target not detected (TND), and elevated viral load (VL) and assessed baseline variables associated with week 144 inflammatory biomarker levels between dolutegravir-lamivudine (DTG/3TC) and tenofovir alafenamide-based regimens (TBRs) in the TANGO study (post hoc). Methods: TANGO is an open-label, multicenter, phase 3 study that randomized adults with VL <50 copies/mL to switch to once-daily fixed-dose DTG/3TC or continue TBR. At baseline and each study visit, the VL was measured. Elevated VL event frequencies were assessed, including "blips." Interleukin 6, D-dimer, high-sensitivity C-reactive protein, soluble CD14, and soluble CD163 were measured at baseline and at week 144. Loge-transformed week 144 biomarker levels were compared between treatment groups using an analysis of covariance model adjusting for baseline variables. Results: High, comparable proportions of participants had VL <40 copies/mL and TND at week 144 (DTG/3TC, 279 of 369 [76%]; TBR, 267 of 372 [72%], intention-to-treat exposed Snapshot analysis; adjusted difference, 3.9% [95% confidence interval, -2.5% to 10.2%]), with similar TND proportions at all postbaseline visits (123 of 369 [33%] vs 101 of 372 [27%], respectively). Similar proportions of DTG/3TC participants had ≥1 postbaseline VL ≥50 copies/mL (28 of 369 [8%] vs 42 of 372 [11%] for TBR), primarily blips (18 of 369 [5%] and 26 of 372 [7%], respectively). Week 144 inflammatory biomarker levels were low and comparable between groups and associated with multiple demographic and baseline characteristics, including baseline biomarker levels, indicating a multifactorial inflammatory response. Conclusions: Week 144 biomarker levels were low and generally comparable between treatment groups, reflecting similar, robust, and durable viral suppression observed using the stringent TND end point. Trial registration:  ClinicalTrials.gov, NCT03446573.

Failure of Non-Invasive Respiratory Support in Patients with SARS-CoV-2.

INTRODUCTION: The objective of this study is to assess the failure of therapies with HFNO (high-flow nasal oxygen), CPAP, Bilevel, or combined therapy in patients with hypoxemic acute respiratory failure due to SARS-CoV-2 during their hospitalization. METHODS: This was a retrospective and observational study of SARS-CoV-2-positive patients who required non-invasive respiratory support (NIRS) at the Reina Sofía General University Hospital of Murcia between March 2020 and May 2021. RESULTS: Of 7355 patients, 197 (11.8%) were included; 95 of them failed this therapy (48.3%). We found that during hospitalization in the ward, the combined therapy of HFNO and CPAP had an overall lower failure rate and the highest treatment with Bilevel (p = 0.005). In the comparison of failure in therapy without two levels of airway pressure, HFNO, CPAP, and combined therapy of HFNO with CPAP, (35.6% of patients) presented with 24.2% failure, compared to those who had two levels of pressure with Bilevel and combined therapy of HFNO with Bilevel (64.4% of patients), with 75.8% associated failure (OR: 0, 374; CI 95%: 0.203-0.688. p = 0.001). CONCLUSIONS: The use of NIRS during conventional hospitalization is safe and effective in patients with respiratory failure secondary to SARS-CoV-2 infection. The therapeutic strategy of Bilevel increases the probability of failure, with the combined therapy strategy of CPAP and HFNO being the most promising option.

Comparative effectiveness and drug survival of biosimilar infliximab CPT-13 vs. reference infliximab in inflammatory bowel disease: A retrospective cohort study.

BACKGROUND: Studies have investigated the efficacy and safety of switching to the biosimilar infliximab (CT-P13) in patients with inflammatory bowel disease (IBD). However, there is limited research directly comparing the effectiveness, drug survival, and pharmacokinetic profiles of the reference infliximab (IFX) and CT-P13 in real clinical settings. OBJECTIVE: To compare the effectiveness and drug survival of CPT-13 and reference IFX at weeks 26 and 52, and to determine the pharmacokinetic profiles and safety profile in real-world settings. METHODS: A retrospective observational cohort analysis was conducted at a single center. The study compared the proportion of patients achieving clinical remission and experiencing poor clinical outcomes at weeks 26 and 52. The drug survival rate of CT-P13 and reference infliximab was also assessed during the follow-up period. RESULTS: A total of 153 patients were included in the study, 39.2% receiving CPT-13 and 60.8% reference IFX. At week 26, clinical remission rates were 66.7% (CPT-13: 74.4% vs. reference IFX: 62.3%, p=0.178), and at week 52, they were 64% (CPT-13: 85.4% vs. reference IFX: 63.0%, p=0.012). Subgroup analysis with therapeutic drug monitoring (TDM) found no significant differences at week 26 (CPT-13: 74.4% vs. reference IFX: 58.8%, p=0.235) or at week 52 (CPT-13: 85.4% vs. reference IFX: 68.8%, p=0.153). CONCLUSION: Our study demonstrates comparable efficacy, drug survival, pharmacokinetic profiles, and incidence of immunogenicity between both drugs in a real clinical setting. Further studies with greater statistical power are needed to validate these findings.

Impact of proactive therapeutic drug monitoring of infliximab during the induction phase in IBD patients. A Bayesian approach.

BACKGROUND AND OBJECTIVES: there is increasing evidence that proactive therapeutic drug monitoring in induction is useful to improve the control of inflammatory bowel disease (IBD), although it remains controversial. The primary objective of the study was to assess the short-term outcomes of proactive Bayesian therapeutic drug monitoring (TDM) during induction, to optimize infliximab (IFX) maintenance dose. METHODS: retrospective observational cohort of IBD patients > 18 years. They were divided into two cohorts, standard therapy group (ST-group), with clinically based dose adjustment, and monitoring group (iTDM-group), with pharmacokinetic parameters calculated by Bayesian prediction at week 6 and individualized dosage regimens thereafter. In patients with an infliximab trough level (ITL) at week 6 below the optimal therapeutic range, the dose adjustment was performed at the first maintenance dose. RESULTS: a total of 153 patients were included, 40 in the iTDM-group. Median ITL at week 6 during the induction period was 12.8 µg/ml (IRQ: 12.7) in this group. Only 16 patients (40.0 %) had ITL ≥ 15 µg/ml. Half of the patients (50.3 %) received intensified maintenance therapy during the study period (57.5 % iTDM vs 47.8 % ST, p = 0.291). The proportion of patients achieving primary response at week 14 was 51.8 %. When comparing the two groups, this proportion was higher in the iTDM group (74.3 % vs 44.2 %, p = 0.002). With regards to the variable "poor clinical outcomes" at week 26, this proportion was lower in the iTDM group (3.3 % iTDM vs 21.1 % ST, p = 0.024). CONCLUSIONS: proactive therapeutic drug monitoring using Bayesian approach is associated with higher primary response rates and fewer short-term complications.

Impact of proactive therapeutic drug monitoring of infliximab during the induction phase in IBD patients. A Bayesian approach

Background and objectives: there is increasing evidence that proactive therapeutic drug monitoring in induction is useful to improve the control of inflammatory bowel disease (IBD), although it remains controversial. The primary objective of the study was to assess the short-term outcomes of proactive Bayesian therapeutic drug monitoring (TDM) during induction, to optimize infliximab (IFX) maintenance dose. Methods: retrospective observational cohort of IBD patients > 18 years. They were divided into two cohorts, standard therapy group (ST-group), with clinically based dose adjustment, and monitoring group (iTDM-group), with pharmacokinetic parameters calculated by Bayesian prediction at week 6 and individualized dosage regimens thereafter. In patients with an infliximab trough level (ITL) at week 6 below the optimal therapeutic range, the dose adjustment was performed at the first maintenance dose. Results: a total of 153 patients were included, 40 in the iTDM-group. Median ITL at week 6 during the induction period was 12.8 µg/ml (IRQ: 12.7) in this group. Only 16 patients (40.0 %) had ITL ≥ 15 µg/ml. Half of the patients (50.3 %) received intensified maintenance therapy during the study period (57.5 % iTDM vs 47.8 % ST, p = 0.291). The proportion of patients achieving primary response at week 14 was 51.8 %. When comparing the two groups, this proportion was higher in the iTDM group (74.3 % vs 44.2 %, p = 0.002). With regards to the variable “poor clinical outcomes” at week 26, this proportion was lower in the iTDM group (3.3 % iTDM vs 21.1 % ST, p = 0.024). Conclusions: proactive therapeutic drug monitoring using Bayesian approach is associated with higher primary response rates and fewer short-term complications (AU)

Identification of COVID-19 patients at risk of hospital admission and mortality: a European multicentre retrospective analysis of mid-regional pro-adrenomedullin.

BACKGROUND: Mid-Regional pro-Adrenomedullin (MR-proADM) is an inflammatory biomarker that improves the prognostic assessment of patients with sepsis, septic shock and organ failure. Previous studies of MR-proADM have primarily focussed on bacterial infections. A limited number of small and monocentric studies have examined MR-proADM as a prognostic factor in patients infected with SARS-CoV-2, however there is need for multicenter validation. An evaluation of its utility in predicting need for hospitalisation in viral infections was also performed. METHODS: An observational retrospective analysis of 1861 patients, with SARS-CoV-2 confirmed by RT-qPCR, from 10 hospitals across Europe was performed. Biomarkers, taken upon presentation to Emergency Departments (ED), clinical scores, patient demographics and outcomes were collected. Multiclass random forest classifier models were generated as well as calculation of area under the curve analysis. The primary endpoint was hospital admission with and without death. RESULTS: Patients suitable for safe discharge from Emergency Departments could be identified through an MR-proADM value of ≤ 1.02 nmol/L in combination with a CRP (C-Reactive Protein) of ≤ 20.2 mg/L and age ≤ 64, or in combination with a SOFA (Sequential Organ Failure Assessment) score < 2 if MR-proADM was ≤ 0.83 nmol/L regardless of age. Those at an increased risk of mortality could be identified upon presentation to secondary care with an MR-proADM value of > 0.85 nmol/L, in combination with a SOFA score ≥ 2 and LDH > 720 U/L, or in combination with a CRP > 29.26 mg/L and age ≤ 64, when MR-proADM was > 1.02 nmol/L. CONCLUSIONS: This international study suggests that for patients presenting to the ED with confirmed SARS-CoV-2 infection, MR-proADM in combination with age and CRP or with the patient's SOFA score could identify patients at low risk where outpatient treatment may be safe.

[Health impact of COVID pandemic. SESPAS Report 2022]. / El impacto de la pandemia de COVID-19 sobre la salud. Informe SESPAS 2022.

OBJECTIVE: The World Health Organization declared the global SARS-CoV-2 infection a pandemic on March 11, 2020. The objective of this paper is to present its impact in terms of physical and mental health 22 months later. METHOD: We have reviewed results from published meta-analysis and systematic reviews, and some individual articles on specific aspects of special interest. National information on infection comes for the Red Nacional de Vigilancia Epidemiológica (RENAVE). RESULTS: Up to the end of October, more than 250 million infections and 5 million deaths had been reported globally. In Spain, 4.7 million infections have been documented although the real figure might be above 7 million. The pandemic has reduced life expectancy, and its effects have been especially dramatic in people with comorbidities and the elderly. There is a worsening of mental health in the general population. It is foreseeable that some groups, such as health professionals, mostly women, and front-line workers, may have a greater risk of developing mental health pathologies. The pandemic and the control measures have had other undesirable consequences such as a decrease in healthcare utilization, an increase in sedentary lifestyle or an increase in gender violence. In addition to its immediate effect on morbidity and mortality, the control measures have damaged the overall health status of the global population. CONCLUSIONS: Longitudinal studies are necessary to determine the mid and long consequences of the pandemic and the control measures, and to identify and evaluate effective health interventions.

Circulating suPAR associates with severity and in-hospital progression of COVID-19.

BACKGROUND: COVID-19 disease progression is characterized by hyperinflammation and risk stratification may aid in early aggressive treatment and advanced planning. The aim of this study was to assess whether suPAR and other markers measured at hospital admission can predict the severity of COVID-19. METHODS: The primary outcome measure in this international, multi-centre, prospective, observational study with adult patients hospitalized primarily for COVID-19 was the association of WHO Clinical Progression Scale (WHO-CPS) with suPAR, ferritin, CRP, albumin, LDH, eGFR, age, procalcitonin, and interleukin-6. Admission plasma suPAR levels were determined using the suPARnostic® ELISA and suPARnostic® Turbilatex assays. RESULTS: Seven hundred and sixty-seven patients, 440 (57.4%) males and 327 (42.6%) females, were included with a median age of 64 years. Log-suPAR levels significantly correlated with WHO-CPS score, with each doubling of suPAR increasing the score by one point (p < .001). All the other markers were also correlated with WHO-CPS score. Admission suPAR levels were significantly lower in survivors (7.10 vs. 9.63, 95% CI 1.47-3.59, p < .001). A linear model (SALGA) including suPAR, serum albumin, serum lactate dehydrogenase, eGFR, and age can best estimate the WHO-CPS score and survival. Combining all five parameters in the SALGA model can improve the accuracy of discrimination with an AUC of 0.80 (95% CI: 0.759-0.836). CONCLUSIONS: suPAR levels significantly correlated with WHO-CPS score, with each doubling of suPAR increasing the score by one point. The SALGA model may serve as a quick tool for predicting disease severity and survival at admission.

Initiation of long-acting cabotegravir plus rilpivirine as direct-to-injection or with an oral lead-in in adults with HIV-1 infection: week 124 results of the open-label phase 3 FLAIR study.

BACKGROUND: Previous work established non-inferiority of switching participants who were virologically suppressed from daily oral standard of care to monthly long-acting intramuscular injections of cabotegravir plus rilpivirine over 96 weeks following a cabotegravir plus rilpivirine oral lead-in. Here, we report an evaluation of switching participants from standard of care oral regimens to long-acting cabotegravir plus rilpivirine via direct-to-injection or oral lead-in pathways. METHODS: This study reports the week 124 results of the FLAIR study, an ongoing phase 3, randomised, open-label, multicentre (11 countries) trial. Antiretroviral therapy (ART)-naive participants who were virologically suppressed (HIV-1 RNA <50 copies per mL) during the 20-week induction phase with standard of care were randomly assigned (1:1) to continue the standard of care oral regimen or switch to long-acting cabotegravir plus rilpivirine (283 per group) in the 100-week maintenance phase. Randomisation was stratified by sex at birth and baseline (pre-induction) HIV-1 RNA (<100 000 or ≥100 000 copies per mL). Participants randomly assigned to long-acting therapy at baseline received a cabotegravir (30 mg) plus rilpivirine (25 mg) once daily oral lead-in for at least 4 weeks before first injection and could choose to continue long-acting cabotegravir (400 mg) plus rilpivirine (600 mg) every 4 weeks from week 100 or withdraw. At week 100, participants in the oral comparator ART group, in discussion with the investigator, could elect to switch to long-acting therapy (extension switch population), either direct-to-injection or with a 4 week oral lead-in (oral lead-in group), or withdraw. Week 124 endpoints included plasma HIV-1 RNA 50 or more copies per mL and less than 50 copies per mL (US Food and Drug Administration [FDA] Snapshot), confirmed virological failure (two consecutive HIV-1 RNA ≥200 copies per mL), and safety and tolerability. The study is registered at ClinicalTrials.gov, NCT02938520. FINDINGS: Screening occurred between Oct 27, 2016, and March 24, 2017. At week 100, 232 (92%) of 253 participants transitioned to long-acting cabotegravir plus rilpivirine in the extension phase (111 [48%] in the direct-to-injection group and 121 [52%] in the oral lead-in group; extension switch population). 243 (86%) of the 283 who were randomly assigned to the long-acting therapy group continued the long-acting regimen into the extension phase. One (<1%) participant in each extension switch group had 50 or more HIV-1 RNA copies per mL; 110 (99%) participants in the direct-to-injection group and 113 (93%) participants in the oral lead-in group remained suppressed (HIV-1 RNA <50 copies per mL) at the week 124 Snapshot. The lower suppression rates in the oral lead-in group were driven by non-virological reasons. For participants in the randomly assigned long-acting group, 227 (80%) of 283 participants remained suppressed; at the week 124 Snapshot, 14 (5%) participants had HIV-1 RNA 50 or more copies per mL, including five additional participants since the week 96 analysis. The remaining 42 (15%) participants in the randomly assigned long-acting group had no virological data. Adverse events leading to withdrawal were infrequent, occurring in three (1%) participants in the extension switch population (one in the direct-to-injection group and two in the oral lead-in group) after 24 weeks of cabotegravir plus rilpivirine therapy, and 15 (5%) participants in the randomly assigned long-acting group up to 124 weeks of therapy. No deaths occurred in the extension phase. Overall, cabotegravir plus rilpivirine adverse event type, severity, and frequency were similar across all groups. Injection site reactions were the most common adverse event, occurring after 914 (21%) of 4442 injections in the extension switch population and 3732 (21%) of 17 392 injections in the randomly assigned long-acting group. Injection site reactions were mostly classified as mild-to-moderate in severity and decreased in incidence over time. Four (2%) of 232 participants in the extension switch population and seven (2%) of 283 in the randomly assigned long-acting group withdrew due to injection-related reasons. INTERPRETATION: After 24 weeks of follow-up, switching to long-acting treatment with or without an oral lead-in phase had similar safety, tolerability, and efficacy, supporting future evaluation of the simpler direct-to-injection approach. The week 124 results for participants randomly assigned originally to the long-acting therapy show long-acting cabotegravir plus rilpivirine remains a durable maintenance therapy with a favourable safety profile. FUNDING: ViiV Healthcare and Janssen Research & Development.

Circulating MR-proADM levels, as an indicator of endothelial dysfunction, for early risk stratification of mid-term mortality in COVID-19 patients.

OBJECTIVES: Thromboinflammation, resulting from a complex interaction between thrombocytopathy, coagulopathy, and endotheliopathy, contributes to increased mortality in COVID-19 patients. MR-proADM, as a surrogate of adrenomedullin system disruption, leading to endothelial damage, has been reported as a promising biomarker for short-term prognosis. We evaluated the role of MR-proADM in the mid-term mortality in COVID-19 patients. METHODS: A prospective, observational study enrolling COVID-19 patients from August to October 2020. A blood sample for laboratory test analysis was drawn on arrival in the emergency department. The primary endpoint was 90-day mortality. The area under the curve (AUC) and Cox regression analyses were used to assess discriminatory ability and association with the endpoint. RESULTS: A total of 359 patients were enrolled, and the 90-day mortality rate was 8.9%. ROC AUC for MR-proADM predicting 90-day mortality was 0.832. An optimal cutoff of 0.80 nmol/L showed a sensitivity of 96.9% and a specificity of 58.4%, with a negative predictive value of 99.5%. Circulating MR-proADM levels (inverse transformed), after adjusting by a propensity score including eleven potential confounders, were an independent predictor of 90-day mortality (HR: 0.162 [95% CI: 0.043-0.480]) CONCLUSIONS: Our data confirm that MR-proADM has a role in the mid-term prognosis of COVID-19 patients and might assist physicians with risk stratification.

Effect of Dietary Supplementation with a Natural Extract of Sclerocarya birrea on Glycemic Metabolism in Subjects with Prediabetes: A Randomized Double-Blind Placebo-Controlled Study.

A randomized, double-blind, placebo-controlled study was conducted with the primary objective of assessing the effect of a natural extract of Sclerocarya birrea on glucose metabolism in subjects with prediabetes. The duration of the study was 90 days. Thirty-three subjects assigned to the experimental group (daily ingestion of 100 mg of the nutraceutical product) and 34 assigned to the placebo group completed the study. There were 36 men and 31 women with a mean age of 32.3 ± 14.1 years. In the area under the curve (AUC) of the oral glucose tolerance test (OGTT), statistically significant decreases in the experimental group at 40 and 90 days as compared with baseline were found, whereas significant changes in the placebo group were not observed. Within-group differences were statistically significant in favor of the experimental group for glucose peak at OGTT, serum insulin, insulin resistance markers, and flow-mediated dilation. Changes in lipid and anthropometric parameters were not observed, although there was a trend for lower cholesterol levels and a decrease in body weight in the experimental group. Decreases in systolic blood pressure were also higher among subjects in the experimental group. This exploratory study confirms the antidiabetic activity of Sclerocarya birrea in prediabetes. Further studies using better measurements of beta-cell function are needed to clarify the underlying mechanisms of the hypoglycemic effect of this natural compound.

Effect of a Combination of Citrus Flavones and Flavanones and Olive Polyphenols for the Reduction of Cardiovascular Disease Risk: An Exploratory Randomized, Double-Blind, Placebo-Controlled Study in Healthy Subjects.

A single-center, randomized, double-blind controlled trial was conducted to assess the efficacy of a food supplement based on a combination of grapefruit, bitter orange, and olive extracts administered for eight weeks (n = 51) versus placebo (n = 45) on reduction of cardiovascular risk in healthy volunteers. Study variables included flow-mediated vasodilation (FMD), blood pressure (BP), lipid profile, thrombotic status, oxidative stress biomarkers, inflammation-related biomarkers, anthropometric variables, quality of life, and physical activity. The per-protocol data set was analyzed. In the active product group, there were statistically significant within-group differences at eight weeks as compared with baseline in FMD, systolic and diastolic BP, total cholesterol, LDL-C, LDL-oxidase, oxidized/reduced glutathione ratio, protein carbonyl, and IL-6. Significant between-group differences in these variables were also found. Significant changes in anthropometric variables and quality of life were not observed in the study groups. Changes in the level of physical activity were not recorded. Treatment with the active product was well tolerated. All these findings, taken together, support a beneficial effect of supplementation with a mixture of grapefruit, bitter orange fruits, and olive leaf extracts on underlying mechanisms that may interact each other to decrease the cardiovascular risk in healthy people.

Prognostic value of pro-adrenomedullin and NT-proBNP in patients referred from the emergency department with influenza syndrome. / Valor pronóstico de la proadrenomedulina y el NT-proBNP en los pacientes procedentes de urgencias con síndrome gripal.

OBJECTIVES: To assess the prognostic value of procalcitonin (PTC), C-reactive protein (CRP), N-terminal prohormone of brain natriuretic peptide (NT-proBNP), and mid-regional pro-adrenomedullin (MR-proADM) in patients with influenza syndrome. MATERIAL AND METHODS: Prospective study in patients admitted from the emergency department with influenza syndrome. Biomarker concentrations were measured in the first 24 h after admission and a test for influenza. The results were analyzed for ability to predict a hospital stay longer than 7 days, intensive care unit admission, or in-hospital death. RESULTS: Ninety-eight patients were included; the prognosis of 44 (44.9%) was classified as poor. The areas under the receiving operator characteristic curve were 0.68 (95% CI, 0.56-0.80) for NT-proBNP, 0.73 (95% CI, 0.62-0.84) for MR-proADM, and nonsignificant for PCT and CRP. The following variables were independently associated with a poor prognosis: pneumonia (OR, 7.46 [95% CI, 2.08-26.73]; P=.002), heart failure (OR, 5.16 [95% CI, 1.35-19.74]; P=.016), and NT-proBNP > 580 pg/mL (OR, 4.68 [95% CI, 1.53-14.26]; P=.006). In the 53 patients with confirmed A(H1N1) influenza, only NT-proBNP was an independent predictor of prognosis (adjusted OR, 5.75 [95% CI, 1.46- 22.61]; P=.012). CONCLUSION: NT-proBNP and MR-proADM were the only biomarkers with prognostic value. Only NT-proBNP was a useful predictor in patients with confirmed influenza.

OBJETIVO: Analizar el valor pronóstico de la procalcitonina (PCT), la proteína C reactiva (PCR), el NT-proBNP y la región medial de la proadrenomedulina (MR-proADM) en pacientes hospitalizados con síndrome gripal. METODO: Estudio prospectivo realizado en pacientes hospitalizados desde urgencias por síndrome gripal. Se analizaron las concentraciones de biomarcadores en las primeras 24 h de ingreso y el test de gripe y se analizó su capacidad predictiva de mal pronóstico: estancia superior a 7 días, ingreso en unidad de cuidados intensivos o fallecimiento intrahospitalario. RESULTADOS: Se incluyeron 98 pacientes, 44 (44,9%) de ellos con mal pronóstico. Las áreas bajo la curva COR para mal pronóstico fueron de 0,68 (IC 95% 0,56-0,80) para NT-proBNP y de 0,73 (IC 95% 0,62-0,84) para la MRproADM, y no significativas para PCT y PCR. Las variables asociadas independientemente con mal pronóstico fueron: neumonía (OR 7,46 [IC 95% 2,08-26,73]; p = 0,002), insuficiencia cardiaca (OR 5,16 [IC 95% 1,35-19,74]; p = 0,016) y NT-proBNP > 580 pg/ml (OR 4,68 [IC 95% 1,53-14,26]; p = 0,006). En los 53 pacientes con gripe A(H1N1) confirmada, solo el NT-proBNP tuvo un valor pronóstico independiente (OR ajustado 5,75 [IC 95% 1,46-22,61]; p = 0,012). CONCLUSIONES: En pacientes con síndrome gripal, el NT-proBNP y la MR-proADM fueron los únicos biomarcadores con valor pronóstico, y solo el primero de ellos mantuvo esta asociación en pacientes con gripe confirmada.

Valor pronóstico de la proadrenomedulina y el NT-proBNP en los pacientes procedentes de urgencias con síndrome gripal / Prognostic value of pro-adrenomedullin and NT-proBNP in patients referred from the emergency department with influenza syndrome

Objetivos: Analizar el valor pronóstico de la procalcitonina (PCT), la proteína C reactiva (PCR), el NT-proBNP y la región medial de la proadrenomedulina (MR-proADM) en pacientes hospitalizados con síndrome gripal. Método: Estudio prospectivo realizado en pacientes hospitalizados desde urgencias por síndrome gripal. Se analizaron las concentraciones de biomarcadores en las primeras 24 h de ingreso y el test de gripe y se analizó su capacidad predictiva de mal pronóstico: estancia superior a 7 días, ingreso en unidad de cuidados intensivos o fallecimiento intrahospitalario. Resultados: Se incluyeron 98 pacientes, 44 (44,9%) de ellos con mal pronóstico. Las áreas bajo la curva COR para mal pronóstico fueron de 0,68 (IC 95% 0,56-0,80) para NT-proBNP y de 0,73 (IC 95% 0,62-0,84) para la MRproADM, y no significativas para PCT y PCR. Las variables asociadas independientemente con mal pronóstico fueron: neumonía (OR 7,46 [IC 95% 2,08-26,73]; p = 0,002), insuficiencia cardiaca (OR 5,16 [IC 95% 1,35-19,74]; p = 0,016) y NT-proBNP > 580 pg/ml (OR 4,68 [IC 95% 1,53-14,26]; p = 0,006). En los 53 pacientes con gripe A(H1N1) confirmada, solo el NT-proBNP tuvo un valor pronóstico independiente (OR ajustado 5,75 [IC 95% 1,46-22,61]; p = 0,012). Conclusiones: En pacientes con síndrome gripal, el NT-proBNP y la MR-proADM fueron los únicos biomarcadores con valor pronóstico, y solo el primero de ellos mantuvo esta asociación en pacientes con gripe confirmada

Objectives: To assess the prognostic value of procalcitonin (PTC), C-reactive protein (CRP), N-terminal prohormone of brain natriuretic peptide (NT-proBNP), and mid-regional pro-adrenomedullin (MR-proADM) in patients with influenza syndrome. Methods: Prospective study in patients admitted from the emergency department with influenza syndrome. Biomarker concentrations were measured in the first 24 h after admission and a test for influenza. The results were analyzed for ability to predict a hospital stay longer than 7 days, intensive care unit admission, or in-hospital death. Results: Ninety-eight patients were included; the prognosis of 44 (44.9%) was classified as poor. The areas under the receiving operator characteristic curve were 0.68 (95% CI, 0.56-0.80) for NT-proBNP, 0.73 (95% CI, 0.62-0.84) for MR-proADM, and nonsignificant for PCT and CRP. The following variables were independently associated with a poor prognosis: pneumonia (OR, 7.46 [95% CI, 2.08-26.73]; P=.002), heart failure (OR, 5.16 [95% CI, 1.35-19.74]; P=.016), and NT-proBNP > 580 pg/mL (OR, 4.68 [95% CI, 1.53-14.26]; P=.006). In the 53 patients with confirmed A(H1N1) influenza, only NT-proBNP was an independent predictor of prognosis (adjusted OR, 5.75 [95% CI, 1.4622.61]; P=.012). Conclusions: NT-proBNP and MR-proADM were the only biomarkers with prognostic value. Only NT-proBNP was a useful predictor in patients with confirmed influenza

VDR rs2228570 Polymorphism Is Related to Non-Progression to AIDS in Antiretroviral Therapy Naïve HIV-Infected Patients.

BACKGROUND: Vitamin D is a fundamental regulator of host defenses by activating genes related to innate and adaptive immunity. In this study, we analyzed the association among single nucleotide polymorphisms (SNPs) in the vitamin D receptor (VDR) gene, with clinical patterns of AIDS progression in antiretroviral treatment (ART)-naïve HIV-infected patients. METHODS: We conducted a retrospective study in 667 HIV-infected patients, who were classified within three groups according to their AIDS progression pattern (183 long-term non-progressors (LTNPs), 334 moderate progressors (MPs), and 150 rapid progressors (RPs)). Five VDR SNPs (rs11568820, rs4516035, rs2228570, rs1544410, and rs7975232) were genotyped using Agena Bioscience's MassARRAY platform. RESULTS: Significant association results were found for rs2228570. Within all HIV patients, the presence of T allele at VDR rs2228570 SNP was protective against AIDS progression (ordinal outcome) under additive (adjusted odds ratio (aOR) = 0.75; p = 0.009), dominant (aOR = 0.69; p = 0.015), and codominant (aOR = 0.56; p = 0.017) inheritance models. In addition, the same allele was protective under additive and codominant inheritance models when we compared with LTNPs vs. RPs [aOR = 0.64 (p = 0.019) and aOR = 0.37 (p = 0.018), respectively] and when we compared MPs vs. RPs [aOR = 0.72 (p = 0.035) and aOR = 0.45 (p = 0.028), respectively]. CONCLUSIONS: The VDR rs2228570 T allele was related to a lower AIDS progression pattern in ART-naïve HIV-infected patients. These findings expand upon the knowledge about HIV pathogenesis in untreated HIV-infected patients with different clinical outcomes.

Respuesta: El fragmento N-terminal del propéptido natriurético cerebral como predictor de mortalidad en pacientes con neumonía adquirida en la comunidad / Reply: The N-terminal pro brain natriuretic peptide as a predictor of mortality in patients with community acquired pneumonia

No disponible

Usefulness of midregional pro-adrenomedullin as a marker of organ damage and predictor of mortality in patients with sepsis.

BACKGROUND: Midregional proadrenomedullin (MR-proADM) is a prognostic biomarker in patients with community-acquired pneumonia (CAP) and sepsis. In this paper, we examined the ability of MR-proADM to predict organ damage and long-term mortality in sepsis patients, compared to that of procalcitonin, C-reactive protein and lactate. METHODS: This was a prospective observational cohort, enrolling severe sepsis or septic shock patients admitted to internal service department. The association between biomarkers and 90-day mortality was assessed by Cox regression analysis and Kaplan-Meier curves. The accuracy of biomarkers for mortality was determined by area under the receiver operating characteristic curve (AUROC) analysis. RESULTS: A total of 148 patients with severe sepsis, according to the criteria of the campaign to survive sepsis, were enrolled. Eighty-five (57.4%) had sepsis according to the new criteria of Sepsis-3. MR-proADM showed the best AUROC to predict sepsis as defined by the Sepsis-3 criteria (AUROC of 0.771, 95% CI 0.692-0.850, p <0.001) and was the only marker independently associated with Sepsis-3 criteria (OR = 4.78, 95% CI 2.25-10.14; p < 0.001) in multivariate analysis. MR-proADM was the biomarker with the best AUROC to predict mortality in 90 days (AUROC of 0.731, CI 95% 0.612-0.850, p <0.001) and was the only marker that kept its independence [hazard ratio (HR) of 1.4, 95% CI 1.2-1.64, p <0.001] in multivariate analysis. The cut-off point of MR-proADM of 1.8 nmol/L (HR of 4.65, 95% CI 6.79-10.1, p < 0.001) was the one that had greater discriminative capacity to predict 90 days mortality. All patients with MR-proADM concentrations ≤0.60 nmol/L survived up to 90 days. In patients with SOFA ≤ 6, the addition of MR-proADM to SOFA score increased the ability of SOFA to identify non-survivors, AUROC of 0.65 (CI 95% 0.537-0.764) and AUROC of 0.700 (CI 95% 0.594-0.800), respectively (p < 0.05 for both). CONCLUSIONS: MR-proADM is a good biomarker in the early identification of high risk septic patients and may contribute to improve the predictive capacity of SOFA scale, especially when scores are low.

El fragmento N-terminal del propéptido natriurético cerebral es el mejor predictor de mortalidad intrahospitalaria en pacientes con sepsis y bajo riesgo de lesión orgánica / The N-terminal pro brain natriuretic peptide is the best predictor of mortality during hospitalization in patients with low risk of sepsis-related organ failure

Introducción: El objetivo de este estudio fue investigar el valor del fragmento N-terminal del propéptido natriurético cerebral (NT-proBNP), proteína C reactiva (PCR) y procalcitonina (PCT) para predecir la mortalidad en pacientes sépticos durante la hospitalización con un riesgo de mortalidad<10% evaluado por el Sepsis-related Organ Failure Assessment (SOFA). Material y métodos: Estudio observacional prospectivo realizado en pacientes hospitalizados con sepsis y riesgo SOFA<10%. Los biomarcadores se obtuvieron en las primeras 72h después del ingreso en el hospital. Todos fueron monitorizados durante la hospitalización o hasta la muerte. Se utilizaron las curvas ROC para determinar el área bajo la curva (ABC) e identificar las mejores concentraciones de corte para predecir la mortalidad. Resultados: Se analizaron un total de 174 pacientes. Diecisiete (9,8%) pacientes murieron durante la hospitalización. El ABC de NT-proBNP fue 0,793 (IC 95% 0,686-0,9; p<0,0005) en comparación con el ABC de la PCR (0,728; IC 95% 0,617-0,839; p=0,004) y el ABC del PCT (0,684; IC 95% 0,557-0,811; p=0,019). Los factores asociados a la mortalidad hospitalaria fueron: tener un NT-proBNP>1.330pg/ml (OR=23,23; IC 95% 2,92-182,25; p=0,003) y tener factores predisponentes para presentar sepsis (OR=3,05; IC 95% 1,3-9,3; p=0,044). Conclusiones: En pacientes con bajo riesgo de mortalidad según la puntuación SOFA, los niveles de NT-proBNP obtenidos en las primeras 72h después del ingreso son un poderoso predictor de mortalidad. Su implementación en la práctica clínica podría mejorar la capacidad predictiva de la puntuación de gravedad clínica en estos pacientes (AU)

Introduction: The purpose of this study was to investigate the value of N-terminal pro brain natriuretic peptide (NT-proBNP), C-reactive protein (CRP) and procalcitonin (PCT) in predicting mortality in septic patients during hospitalization with mortality risk<10% evaluated by Sepsis-related Organ Failure Assessment (SOFA). Material and methods: Prospective, observational study performed in sepsis patients with SOFA risk<10%. We obtained levels of biomarkers in the first 72h after admission in hospital. All patients were monitored during hospitalization or until death. We used ROC curves to determine area under curve (AUC) and identify the best cutoff concentrations to predict mortality. Results: A total of 174 patients were analyzed. Seventeen (9.8%) patients died during hospitalization. The AUC of NT-proBNP was 0.793 (95% CI 0.686-0.9; P<.0005) compared to AUC of CRP (0.728; 95% CI 0.617-0.839; P=.004) and AUC of PCT (0.684; 95% CI 0.557-0.811; P=.019). Factors independently associated with in-hospital mortality were NT-proBNP>1,330pg/ml (OR=23.23; 95% CI 2.92-182.25; P=.003) and to have predisposing factors (OR=3.05; 95% CI 1.3-9.3; P=.044). Conclusions: In patients with low mortality risk according to SOFA score, NT-proBNP obtained in the first 72h after admission prove to be a powerful predictor of mortality. Their implementations in clinical practice would improve the predictive ability of clinical severity scores (AU)