Coronary artery disease as a risk factor for metabolic dysfunction-associated steatotic liver disease and liver fibrosis.

INTRODUCTION AND OBJECTIVES: Patients with metabolic dysfunction-associated steatotic liver disease (MASLD) are at an increased cardiovascular risk. On the contrary, non-alcoholic fatty liver disease (NAFLD) is highly prevalent in patients with coronary heart disease (CHD). However, it is not known whether patients with significant CHD show a higher frequency of liver fibrosis. This study aimed to determine the frequency of MASLD and liver fibrosis in patients with CHD and to assess whether coronary stenosis is significantly associated with MASLD and fibrosis. PATIENTS AND METHODS: This observational and analytical study included adult patients without any known liver disease who underwent coronary angiography for suspected coronary artery disease (Jul 2021-Jul 2022). The presence of significant CHD (> 50% stenosis of at least one coronary artery) was determined. Liver elastography (FibroScan®) was performed up to 6 months after the coronary angiographic study to determine liver fibrosis, a measurement of liver stiffness (> 6.5 Kpa). Fisher's test, Mann-Whitney U test, and logistic regression models were used (p < 0.05). RESULTS: The study included 113 patients (76% men, average age: 63 years [standard deviation: 9.9]), of which 72% presented with significant CHD. The prevalence rate of MASLD was 52%. Liver fibrosis was present in 12% of the patients and all patients in the significant CHD group (p = 0.007). An increase in the number of vessels with significant CHD increased the probability of liver fibrosis (odds ratio, 1.79; 95% confidence interval, 1.06-3.04; p = 0.029). CONCLUSIONS: MASLD is highly prevalent in patients with significant CHD but without known liver damage. These data suggest that MASLD and liver fibrosis should be investigated in patients with CHD. The presence of confounding variables, especially the presence of type 2 diabetes mellitus, should be evaluated in further studies.

Dynamic relative regional lung strain estimated by computed tomography and electrical impedance tomography in ARDS patients.

BACKGROUND: In the acute distress respiratory syndrome (ARDS), specific lung regions can be exposed to excessive strain due to heterogeneous disease, gravity-dependent lung collapse and injurious mechanical ventilation. Computed tomography (CT) is the gold standard for regional strain assessment. An alternative tool could be the electrical impedance tomography (EIT). We aimed to determine whether EIT-based methods can predict the dynamic relative regional strain (DRRS) between two levels of end-expiratory pressure (PEEP) in gravity-non-dependent and dependent lung regions. METHODS: Fourteen ARDS patients underwent CT and EIT acquisitions (at end-inspiratory and end-expiratory) at two levels of PEEP: a low-PEEP based on ARDS-net strategy and a high-PEEP titrated according to EIT. Three EIT-based methods for DRRS were compared to relative CT-based strain: (1) the change of the ratio between EIT ventilation and end-expiratory lung impedance in arbitrary units ([ΔZAU low-PEEP/EELIAU low-PEEP]/[ΔZAU high-PEEP/EELIAU high-PEEP]), (2) the change of ΔZ/EELI ratio calibrated to mL ([ΔZml low-PEEP/EELIml low-PEEP]/[ΔZml high-PEEP/EELIml high-PEEP]) using CT data, and (3) the relative change of ∆ZAU (∆ZAU low-PEEP/∆ZAU high-PEEP). We performed linear regressions analysis and calculated bias and limits of agreement to assess the performance of DRRS by EIT in comparison with CT. RESULTS: The DRRS assessed by (ΔZml low-PEEP/EELIml low-PEEP)/(ΔZml high-PEEP/EELIml high-PEEP) and ∆ZAU low-PEEP/∆ZAU high-PEEP showed good relationship and agreement with the CT method (R2 of 0.9050 and 0.8679, respectively, in non-dependent region; R2 of 0.8373 and 0.6588, respectively, in dependent region; biases ranging from - 0.11 to 0.51 and limits of agreement ranging from - 0.73 to 1.16 for both methods and lung regions). Conversely, DRRS based on EELIAU ([ΔZAU low-PEEP/EELIAU low-PEEP]/[ΔZAU high-PEEP/EELIAU high-PEEP]) exhibited a weak negative relationship and poor agreement with the CT method for both non-dependent and dependent regions (R2 ~ 0.3; bias of 3.11 and 2.08, and limits of agreement of - 2.13 to 8.34 and from - 1.49 to 5.64, respectively). CONCLUSION: Changes in DRRS during a PEEP trial in ARDS patients could be monitored using EIT, based on changes in ΔZmL/EELIml and ∆ZAU. The relative change ∆ZAU offers the advantage of not requiring CT data for calibration.

Mortality in patients with severe COVID-19 who underwent tracheostomy due to prolonged mechanical ventilation.

BACKGROUND: The usefulness of tracheostomy has been questioned in patients with COVID-19 and prolonged invasive mechanical ventilation (IMV). AIM: To compare the 90-day mortality rate of patients who underwent a tracheostomy due prolonged IMV with those that did not receive this procedure. MATERIAL AND METHODS: We studied a historical cohort of 92 patients with COVID-19 and prolonged IMV (> 10 days). The primary outcome was the 90-day mortality rate. Secondary outcomes included days on IMV, hospital/intensive care unit (ICU) length of stay, frequency of nosocomial infections, and thrombotic complications demonstrated by images. A logistic regression was performed to adjust the effect of tracheostomy by SOFA score and days on IMV. RESULTS: Forty six patients aged 54 to 66 years (72% males) underwent tracheostomy. They had a median of two comorbidities, and received the procedure after a median of 20.5 days on IMV (interquartile range: 17-26). 90-day mortality was lower in patients who were tracheostomized than in the control group (6.5% vs. 32.6%, p-value < 0.01). However, after controlling for confounding factors, no differences were found in mortality between both groups (relative risk = 0.303, p-value = 0.233). Healthcare-associated infections and hospital/ICU length of stay were higher in patients with tracheostomy than in controls. Thrombotic complications occurred in 42.4% of the patients, without differences between both groups. No cases of COVID-19 were registered in the healthcare personnel who performed tracheostomies. CONCLUSIONS: In patients with COVID-19 undergoing prolonged IMV, performing a tracheostomy is not associated with excess mortality, and it is a safe procedure for healthcare personnel.

Extracorporeal Membrane Oxygenation for COVID-19-associated Severe Acute Respiratory Distress Syndrome in Chile: A Nationwide Incidence and Cohort Study.

Rationale: The role of and needs for extracorporeal membrane oxygenation (ECMO) at a population level during the coronavirus disease (COVID-19) pandemic have not been completely established. Objectives: To identify the cumulative incidence of ECMO use in the first pandemic wave and to describe the Nationwide Chilean cohort of ECMO-supported patients with COVID-19. Methods: We conducted a population-based study from March 3 to August 31, 2020, using linked data from national agencies. The cumulative incidence of ECMO use and mortality risk of ECMO-supported patients were calculated and age standardized. In addition, a retrospective cohort analysis was performed. Outcomes were 90-day mortality after ECMO initiation, ECMO-associated complications, and hospital length of stay. Cox regression models were used to explore risk factors for mortality in a time-to-event analysis. Measurements and Main Results: Ninety-four patients with COVID-19 were supported with ECMO (0.42 per population of 100,000, 14.89 per 100,000 positive cases, and 1.2% of intubated patients with COVID-19); 85 were included in the cohort analysis, and the median age was 48 (interquartile range [IQR], 41-55) years, 83.5% were men, and 42.4% had obesity. The median number of pre-ECMO intubation days was 4 (IQR, 2-7), the median PaO2/FiO2 ratio was 86.8 (IQR, 64-99) mm Hg, 91.8% of patients were prone positioned, and 14 patients had refractory respiratory acidosis. Main complications were infections (70.6%), bleeding (38.8%), and thromboembolism (22.4%); 52 patients were discharged home, and 33 died. The hospital length of stay was a median of 50 (IQR, 24-69) days. Lower respiratory system compliance and higher driving pressure before ECMO initiation were associated with increased mortality. A duration of pre-ECMO intubation ≥10 days was not associated with mortality. Conclusions: Documenting nationwide ECMO needs may help in planning ECMO provision for future COVID-19 pandemic waves. The 90-day mortality of the Chilean cohort of ECMO-supported patients with COVID-19 (38.8%) is comparable to that of previous reports.

Risky sexual behaviors in adolescents and young adult women with type 1 diabetes: An overlooked problem.

The presence of unprotected sex activity in women living with type 1 diabetes (T1D) who have insufficient glycemic control should be considered as a specific risky behavior. To evaluate risky behaviors, including unprotected sexual activity, sources of information and knowledge related to reproductive health in adolescents and young adult women with T1D (PwT1D) compared to a group of adolescents and young adult women without diabetes (Comparison group). PwT1D and the Comparison group completed a questionnaire with validated measures that assessed reproductive health. PwT1D (n = 115, age = 17.7 ± 3.2 years) and Comparison group (n = 386, age = 18.3 ± 2.9) were recruited. The proportion of women reporting having sex without any contraceptive was similar in both groups (57.1% and 50%, in PwT1D and Comparison group, respectively). The use of non-effective contraceptive was reported in 63.2% and 63.6% of the PwT1D and Comparison group, respectively. Among PwT1D, parents, formal sex education, and friends were the primary source of information on reproductive health. Low levels of knowledge about diabetes and pregnancy were observed in PwT1D. HbA1c level was associated with having at least one sexual activity without any contraception (OR = 1.63, p = 0.039). PwT1D have similar rates of risky behaviors compared to a Comparison group. Sexual risky behaviors should be especially considered in PwT1D with glycemic control above the optimal level. Parents are an important source of reproductive health information for PwT1D. Use of effective contraception should be reinforced in sexually active PwT1D.

Estimation of changes in cyclic lung strain by electrical impedance tomography: Proof-of-concept study.

RATIONALE: Cyclic strain may be a determinant of ventilator-induced lung injury. The standard for strain assessment is the computed tomography (CT), which does not allow continuous monitoring and exposes to radiation. Electrical impedance tomography (EIT) is able to monitor changes in regional lung ventilation. In addition, there is a correlation between mechanical deformation of materials and detectable changes in its electrical impedance, making EIT a potential surrogate for cyclic lung strain measured by CT (StrainCT ). OBJECTIVES: To compare the global StrainCT with the change in electrical impedance (ΔZ). METHODS: Acute respiratory distress syndrome patients under mechanical ventilation (VT 6 mL/kg ideal body weight with positive end-expiratory pressure 5 [PEEP 5] and best PEEP according to EIT) underwent whole-lung CT at end-inspiration and end-expiration. Biomechanical analysis was used to construct 3D maps and determine StrainCT at different levels of PEEP. CT and EIT acquisitions were performed simultaneously. Multilevel analysis was employed to determine the causal association between StrainCT and ΔZ. Linear regression models were used to predict the change in lung StrainCT between different PEEP levels based on the change in ΔZ. MAIN RESULTS: StrainCT was positively and independently associated with ΔZ at global level (P < .01). Furthermore, the change in StrainCT (between PEEP 5 and Best PEEP) was accurately predicted by the change in ΔZ (R2 0.855, P < .001 at global level) with a high agreement between predicted and measured StrainCT . CONCLUSIONS: The change in electrical impedance may provide a noninvasive assessment of global cyclic strain, without radiation at bedside.

Clinical characteristics and in-hospital mortality of patients with COVID-19 in Chile: A prospective cohort study.

AIMS OF THIS STUDY: To describe the Latin American population affected by COVID-19, and to determine relevant risk factors for in-hospital mortality. METHODS: We prospectively registered relevant clinical, laboratory, and radiological data of adult patients with COVID-19, admitted within the first 100 days of the pandemic from a single teaching hospital in Santiago, Chile. The primary outcome was in-hospital mortality. Secondary outcomes included the need for respiratory support and pharmacological treatment, among others. We combined the chronic disease burden and the severity of illness at admission with predefined clinically relevant risk factors. Cox regression models were used to identify risk factors for in-hospital mortality. RESULTS: We enrolled 395 adult patients, their median age was 61 years; 62.8% of patients were male and 40.1% had a Modified Charlson Comorbidity Index (MCCI) ≥5. Their median Sequential Organ Failure Assessment (SOFA) score was 3; 34.9% used a high-flow nasal cannula and 17.5% required invasive mechanical ventilation. The in-hospital mortality rate was 14.7%. In the multivariate analysis, were significant risk factors for in-hospital mortality: MCCI ≥5 (HR 4.39, P < .001), PaO2 /FiO2 ratio ≤200 (HR 1.92, P = .037), and advanced chronic respiratory disease (HR 3.24, P = .001); pre-specified combinations of these risk factors in four categories was associated with the outcome in a graded manner. CONCLUSIONS AND CLINICAL IMPLICATIONS: The relationship between multiple prognostic factors has been scarcely reported in Latin American patients with COVID-19. By combining different clinically relevant risk factors, we can identify COVID-19 patients with high-, medium- and low-risk of in-hospital mortality.

Joint Cardioprotective Effect of Vitamin C and Other Antioxidants against Reperfusion Injury in Patients with Acute Myocardial Infarction Undergoing Percutaneous Coronary Intervention.

Percutaneous coronary intervention (PCI) has long remained the gold standard therapy to restore coronary blood flow after acute myocardial infarction (AMI). However, this procedure leads to the development of increased production of reactive oxygen species (ROS) that can exacerbate the damage caused by AMI, particularly during the reperfusion phase. Numerous attempts based on antioxidant treatments, aimed to reduce the oxidative injury of cardiac tissue, have failed in achieving an effective therapy for these patients. Among these studies, results derived from the use of vitamin C (Vit C) have been inconclusive so far, likely due to suboptimal study designs, misinterpretations, and the erroneous conclusions of clinical trials. Nevertheless, recent clinical trials have shown that the intravenous infusion of Vit C prior to PCI-reduced cardiac injury biomarkers, as well as inflammatory biomarkers and ROS production. In addition, improvements of functional parameters, such as left ventricular ejection fraction (LVEF) and telediastolic left ventricular volume, showed a trend but had an inconclusive association with Vit C. Therefore, it seems reasonable that these beneficial effects could be further enhanced by the association with other antioxidant agents. Indeed, the complexity and the multifactorial nature of the mechanism of injury occurring in AMI demands multitarget agents to reach an enhancement of the expected cardioprotection, a paradigm needing to be demonstrated. The present review provides data supporting the view that an intravenous infusion containing combined safe antioxidants could be a suitable strategy to reduce cardiac injury, thus improving the clinical outcome, life quality, and life expectancy of patients subjected to PCI following AMI.

[Variceal and non-variceal upper gastrointestinal bleeding. Analysis of 249 hospitalized patients]. / Hemorragia digestiva alta variceal y no variceal: mortalidad intrahospitalaria y características clínicas en un hospital universitario (2015-2017).

BACKGROUND: Upper gastrointestinal bleeding (UGIB) is one of the main reasons of hospitalization due to gastrointestinal causes. Reported mortality rates range from 5 to 12%. AIM: To determine hospital mortality and associated risk factors in hospitalized patients with UGIB. To compare the clinical characteristics and outcomes of patients with variceal versus non-variceal UGIB. MATERIAL AND METHODS: Review of medical records of 249 patients (62% males) discharged with the diagnosis of UGIB at a clinical hospital between 2015 to 2017. Demographic and clinical characteristics and adverse clinical outcomes (surgery, length of hospital stay and in-hospital mortality) were recorded. A comparative analysis between patients with Variceal and Non-variceal UGIB was carried out. RESULTS: Seventy two percent of UGIB were non-variceal (peptic ulcer in 44%). Two patients required surgery (both died). Median of length of hospital stay was seven days (interquartile range (IQR) 4-13). Overall hospital mortality was 13 and 4% in variceal and non-variceal UGIB, respectively (p = 0.024). The variables associated with mortality were: red blood cell transfusion (odds ratio (OR): 18.7, p < 0.01), elevated creatinine on admission (OR: 3.30, p = 0.03) and variceal bleeding (OR: 3.23, p = 0.02). CONCLUSIONS: Hospital mortality of UGIB remains high, especially in variceal UGIB. Elevated creatinine levels on admission, the need of transfusion of red blood cells and variceal etiology are risk factors for mortality.

[Surgical complications in cirrhotic patients. Analysis of 102 cases]. / Cirugía en el paciente cirrótico: características clínicas y complicaciones en una cohorte de pacientes chilenos.

BACKGROUND: Cirrhotic patients have an increased surgical risk due to potential intra and postoperative complications. AIM: To describe the clinical characteristics and surgical complications of cirrhotic patients undergoing surgery in a Chilean university hospital. PATIENTS AND METHODS: Review of medical records of 102 cirrhotic patients aged 60 ± 11 years (52% males) who underwent elective or urgency surgery at an university hospital between 2010 and 2016. General, pre-surgical, and post-surgical complications were recorded. RESULTS: The main etiologies of cirrhosis were non-alcoholic steatohepatitis (31%), and alcoholic cirrhosis (28%). Child-Pugh scores were A, B and C in 50, 28 and 22% of cases respectively. Median MELD (Model for End-stage Liver Disease) score was 11 (interquartile range: 10-15). The surgical procedure was elective in 71% of cases, with predominance of abdominal surgery (86%). The American Society of Anesthesiologists (ASA) score was three or more in 52% of patients. The frequency of any adverse outcome was 62%. The frequency increased along with the severity of cirrhosis and when surgery was urgent. The most common complications were acute renal failure (24%), increased ascites (23%) and encephalopathy (22%). Admission to intensive care unit occurred on 26% of patients, with six hospital deaths. CONCLUSIONS: In these patients, surgical complications were common, although with low mortality.

Plasma Antioxidant Potential at Admission is Associated with Length of ICU Stay in Child with Sepsis: A Pilot Study.

OBJECTIVE: To assess the relationship between biomarkers of oxidative stress (OS) and the length of stay in intensive care units (LSICU) in septic children. METHODS: Clinical parameters and biomarkers of OS were measured in 16 children admitted for sepsis in an intensive care unit. The associations between biomarkers of OS and the LSICU were assessed by linear correlation. Multiple linear regression models were constructed to adjust other variables. RESULTS: The mean of LSICU was 7.13 ± 4.17 days. LSICU was associated with the catalase activity (rho =0.56, p-value =0.024) and the ferric reducing ability of plasma (FRAP, r = 0.73, p-value =0.001). However, only FRAP at ICU admission was independently associated with LSICU, which rose 0.21 days for each 10 µmol/l of increase in the FRAP level. CONCLUSION: We conclude for first time that FRAP level at ICU admission is independently associated with LSICU in pediatric patients.

Ionizing Radiation-Induced Oxidative Stress in Computed Tomography-Effect of Vitamin C on Prevention of DNA Damage: PREVIR-C Randomized Controlled Trial Study Protocol.

Exposure to ionizing radiation (IR) is inevitable in various X-ray imaging examinations, with computed tomography (CT) being a major contributor to increased human radiation exposure. Ionizing radiation may cause structural damage to macromolecules, particularly DNA, mostly through an indirect pathway in diagnostic imaging. The indirect pathway primarily involves the generation of reactive oxygen species (ROS) due to water radiolysis induced by IR, leading to DNA damage, including double-strand breaks (DSB), which are highly cytotoxic. Antioxidants, substances that prevent oxidative damage, are proposed as potential radioprotective agents. This Study Protocol article presents the rationale for selecting vitamin C as a preventive measure against CT-associated IR-induced DNA damage, to be investigated in a randomized placebo-controlled trial, with a full in vivo design, using an oral easy-to-use schedule administration in the outpatient setting, for the single CT examination with the highest total global IR dose burden (contrast-enhanced abdomen and pelvis CT). The study also aims to explore the mediating role of oxidative stress, and it has been written in adherence to the Standard Protocol Items recommendations.

Pendelluft in hypoxemic patients resuming spontaneous breathing: proportional modes versus pressure support ventilation.

BACKGROUND: Internal redistribution of gas, referred to as pendelluft, is a new potential mechanism of effort-dependent lung injury. Neurally-adjusted ventilatory assist (NAVA) and proportional assist ventilation (PAV +) follow the patient's respiratory effort and improve synchrony compared with pressure support ventilation (PSV). Whether these modes could prevent the development of pendelluft compared with PSV is unknown. We aimed to compare pendelluft magnitude during PAV + and NAVA versus PSV in patients with resolving acute respiratory distress syndrome (ARDS). METHODS: Patients received either NAVA, PAV + , or PSV in a crossover trial for 20-min using comparable assistance levels after controlled ventilation (> 72 h). We assessed pendelluft (the percentage of lost volume from the non-dependent lung region displaced to the dependent region during inspiration), drive (as the delta esophageal swing of the first 100 ms [ΔPes 100 ms]) and inspiratory effort (as the esophageal pressure-time product per minute [PTPmin]). We performed repeated measures analysis with post-hoc tests and mixed-effects models. RESULTS: Twenty patients mechanically ventilated for 9 [5-14] days were monitored. Despite matching for a similar tidal volume, respiratory drive and inspiratory effort were slightly higher with NAVA and PAV + compared with PSV (ΔPes 100 ms of -2.8 [-3.8--1.9] cm H2O, -3.6 [-3.9--2.4] cm H2O and -2.1 [-2.5--1.1] cm H2O, respectively, p < 0.001 for both comparisons; PTPmin of 155 [118-209] cm H2O s/min, 197 [145-269] cm H2O s/min, and 134 [93-169] cm H2O s/min, respectively, p < 0.001 for both comparisons). Pendelluft magnitude was higher in NAVA (12 ± 7%) and PAV + (13 ± 7%) compared with PSV (8 ± 6%), p < 0.001. Pendelluft magnitude was strongly associated with respiratory drive (ß = -2.771, p-value < 0.001) and inspiratory effort (ß = 0.026, p < 0.001), independent of the ventilatory mode. A higher magnitude of pendelluft in proportional modes compared with PSV existed after adjusting for PTPmin (ß = 2.606, p = 0.010 for NAVA, and ß = 3.360, p = 0.004 for PAV +), and only for PAV + when adjusted for respiratory drive (ß = 2.643, p = 0.009 for PAV +). CONCLUSIONS: Pendelluft magnitude is associated with respiratory drive and inspiratory effort. Proportional modes do not prevent its occurrence in resolving ARDS compared with PSV.

Pharmacological Basis for Abrogating Myocardial Reperfusion Injury Through a Multi-Target Combined Antioxidant Therapy.

The main goal of the treatment for acute myocardial infarction is to achieve reperfusion of the affected myocardial tissue, with percutaneous coronary angioplasty being the gold standard procedure. However, this strategy has been associated with additional heart damage termed "lethal reperfusion injury," which is responsible for up to half of the final infarct size. Among the possible underlying mechanisms that are likely to explain this damage, studies suggest that oxidative stress plays a key role. Although this has not been translated into clinical benefits in most studies, recent preclinical studies reported promising results and a possible synergy with the combined use of vitamin C (VC), N-acetylcysteine (NAC), and deferoxamine (DFO). However, to implement a combined therapy with these drugs for patients requires further studies to understand their pharmacokinetic properties. Available data of the clinical trials have not been validated by looking into the pharmacokinetics in their design. Therefore, this article presents an update and comparison of the evidence for the efficacy of these administration schemes for each drug in cardioprotection, their pharmacokinetic properties and mechanisms of action for their use against "lethal reperfusion injury." To achieve a cardioprotective effect using a new pharmacological strategy before the onset of reperfusion, it is helpful to consider the pharmacokinetics of each drug. In this regard, to design a fast and short pharmacologic therapeutic strategy, theoretically VC and DFO concentrations could be modeled by a one-compartment model whereas NAC could be modeled by a three-compartment model with an initial short half-life.

Autoimmune Hepatitis with Acute Presentation: Clinical, Biochemical, and Histological Features of 126 Patients.

Introduction: Autoimmune hepatitis (AIH) is a chronic liver disease with a relevant inflammatory component and an unknown etiology. Evidence for clinical characteristics and risk factors in large cohorts of patients with acute AIH (AAIH) is lacking. We clinically characterized patients with AAIH, the prevalence of a combined adverse outcome (death or liver transplantation (LT)), and its risk factors. Methods: A retrospective study of adult patients diagnosed with AAIH at three centers (Santiago, Chile; 2000-2018) was conducted. Clinical and laboratory characteristics were obtained. A liver biopsy was performed for all patients. Descriptive statistics and logistic regression models were used. Results: A total of 126 patients were admitted; 77% were female, 33 (26.2%) had a severe presentation, and 14 (11.1%) had a fulminant presentation. Overall, 24 patients (19.0%) lacked typical autoantibodies, and 26.2% had immunoglobulin G levels in the normal range. The most frequent histological findings were plasma cells (86.5%), interface hepatitis (81.7%), and chronic hepatitis (81.0%). Rosettes were uncommon (35.6%). Advanced fibrosis was present in 27% of patients. Combined adverse outcomes occurred in 7.9% of cases, all fulminant with histological cholestasis. Alkaline phosphatase, bilirubin, and prothrombin less than 50% were independent risk factors for in-hospital death or LT (p value <0.05). Although corticosteroid treatment was associated with better outcomes (OR 0.095, p value = 0.013), more severe patients were less likely to receive this therapy. Discussion. In this large cohort of patients with AAIH, clinical characteristics differ from those reported in patients with chronic AIH. Fulminant hepatitis, histological cholestasis, alkaline phosphatase, bilirubin, and prothrombin were associated with death/LT.

Electroencephalography spectral edge frequency and suppression rate-guided sedation in patients with COVID-19: A randomized controlled trial.

Background: Sedation in coronavirus disease 2019 (COVID-19) patients has been identified as a major challenge. We aimed to investigate whether the use of a multiparameter electroencephalogram (EEG) protocol to guide sedation in COVID-19 patients would increase the 30-day mechanical ventilation-free days (VFD). Methods: We conducted a double-blind randomized clinical trial. We included patients with severe pneumonia due to COVID-19 who required mechanical ventilation (MV) and deep sedation. We randomized to the control (n = 25) or multiparameter group (n = 25). Sedation in the intervention group was administered following the standard institutional protocols together with a flow chart designed to reduce the propofol administration dose if the EEG suppression rate was over 2% or the spectral edge frequency 95 (SEF95) was below 10 Hz. We performed an intention-to-treat analysis to evaluate our primary outcome (30-day VFD). Results: There was no difference in VFD at day 30 (median: 11 [IQR 0-20] days in the control group vs. 0 [IQR 0-21] days in the BIS multiparameter group, p = 0.87). Among secondary outcomes, we documented a 17% reduction in the total adjusted propofol administered during the first 5 days of the protocol [median: 2.3 (IQR 1.9-2.8) mg/k/h in the control group vs. 1.9(IQR 1.5-2.2) mg/k/h in the MP group, p = 0.005]. This was accompanied by a higher average BIS value in the intervention group throughout the treatment period. Conclusion: A sedation protocol guided by multivariate EEG-derived parameters did not increase the 30-day VFD. However, the intervention led to a reduction in total propofol administration.

Effects of 2019's social protests on emergency health services utilization and case severity in Santiago, Chile: a time-series analysis.

Background: On October 18th, 2019, protestors gathered across Chile to call for social equity, resulting in widespread civil unrest and violent confrontation with the police. In this study, we quantify the effects of the 2019 Chilean protests on emergency health services utilization and inpatient admission in Santiago. Methods: We used weekly emergency department (ED) admissions (2015-2019) from three large public hospitals near the focal point of protests in Santiago. The exposure period was from October 18th to December 31st, 2019. The outcomes were the number of weekly consultations and hospitalizations by trauma and respiratory causes and the proportion of hospitalizations among consultants per 1,000. We implemented Bayesian structural time series models to calculate the absolute and relative effects and 95% credible intervals (CrI). Findings: During the first ten weeks of protests ED consultations declined on average by 14% for trauma (95%CrI: -40·2%, 11·5%) and 30% for respiratory causes (95%CrI: -89·4%, 30·2%), 7% for respiratory hospitalizations (95%CrI: -43·6%, 30·8%); however, none of these three results were statistically distinguishable from the null. Trauma hospitalizations, on the other hand, increased by 15% (95%CrI: 4·0%, 26·4%), and the proportion of hospitalizations per consultations increased by 40% for trauma (95%CrI: 13·1%, 68·0%) and 59% for respiratory causes (95%CrI: 29·4%, 87·9%). Interpretation: The 2019 Chilean protests affected the use of emergency health services by increasing the trauma hospitalizations and the case hospitalization ratio per 1,000 consultations for trauma and respiratory causes. Crowd-control protocols must be reviewed to prevent the negative effects of civil unrest.

Inflammatory biomarkers and pendelluft magnitude in ards patients transitioning from controlled to partial support ventilation.

The transition from controlled to partial support ventilation is a challenge in acute respiratory distress syndrome (ARDS) patients due to the risks of patient-self-inflicted lung injury. The magnitude of tidal volume (VT) and intrapulmonary dyssynchrony (pendelluft) are suggested mechanisms of lung injury. We conducted a prospective, observational, physiological study in a tertiary academic intensive care unit. ARDS patients transitioning from controlled to partial support ventilation were included. On these, we evaluated the association between changes in inflammatory biomarkers and esophageal pressure swing (ΔPes), transpulmonary driving pressure (ΔPL), VT, and pendelluft. Pendelluft was defined as the percentage of the tidal volume that moves from the non-dependent to the dependent lung region during inspiration, and its frequency at different thresholds (- 15, - 20 and - 25%) was also registered. Blood concentrations of inflammatory biomarkers (IL-6, IL-8, TNF-α, ANGPT2, RAGE, IL-18, Caspase-1) were measured before (T0) and after 4-h (T4) of partial support ventilation. Pendelluft, ΔPes, ΔPL and VT were recorded. Nine out of twenty-four patients (37.5%) showed a pendelluft mean ≥ 10%. The mean values of ΔPes, ΔPL, and VT were - 8.4 [- 6.7; - 10.2] cmH2O, 15.2 [12.3-16.5] cmH2O and 8.1 [7.3-8.9] m/kg PBW, respectively. Significant associations were observed between the frequency of high-magnitude pendelluft and IL-8, IL-18, and Caspase-1 changes (T0/T4 ratio). These results suggest that the frequency of high magnitude pendelluft may be a potential determinant of inflammatory response related to inspiratory efforts in ARDS patients transitioning to partial support ventilation. Future studies are needed to confirm these results.

Continuous prolonged prone positioning in COVID-19-related ARDS: a multicenter cohort study from Chile.

BACKGROUND: Prone positioning is currently applied in time-limited daily sessions up to 24 h which determines that most patients require several sessions. Although longer prone sessions have been reported, there is scarce evidence about the feasibility and safety of such approach. We analyzed feasibility and safety of a continuous prolonged prone positioning strategy implemented nationwide, in a large cohort of COVID-19 patients in Chile. METHODS: Retrospective cohort study of mechanically ventilated COVID-19 patients with moderate-to-severe acute respiratory distress syndrome (ARDS), conducted in 15 Intensive Care Units, which adhered to a national protocol of continuous prone sessions ≥ 48 h and until PaO2:FiO2 increased above 200 mm Hg. The number and extension of prone sessions were registered, along with relevant physiologic data and adverse events related to prone positioning. The cohort was stratified according to the first prone session duration: Group A, 2-3 days; Group B, 4-5 days; and Group C, > 5 days. Multivariable regression analyses were performed to assess whether the duration of prone sessions could impact safety. RESULTS: We included 417 patients who required a first prone session of 4 (3-5) days, of whom 318 (76.3%) received only one session. During the first prone session the main adverse event was grade 1-2 pressure sores in 97 (23.9%) patients; severe adverse events were infrequent with 17 non-scheduled extubations (4.2%). 90-day mortality was 36.2%. Ninety-eight patients (24%) were classified as group C; they exhibited a more severe ARDS at baseline, as reflected by lower PaO2:FiO2 ratio and higher ventilatory ratio, and had a higher rate of pressure sores (44%) and higher 90-day mortality (48%). However, after adjustment for severity and several relevant confounders, prone session duration was not associated with mortality or pressure sores. CONCLUSIONS: Nationwide implementation of a continuous prolonged prone positioning strategy for COVID-19 ARDS patients was feasible. Minor pressure sores were frequent but within the ranges previously described, while severe adverse events were infrequent. The duration of prone session did not have an adverse effect on safety.