Extracorporeal membrane oxygenation versus invasive ventilation in patients with COVID-19 acute respiratory distress syndrome and pneumomediastinum: A cohort trial.

BACKGROUND: Patients with severe respiratory failure due to COVID-19 who are not under mechanical ventilation may develop severe hypoxemia when complicated with spontaneous pneumomediastinum (PM). These patients may be harmed by invasive ventilation. Alternatively, veno-venous (V-V) extracorporeal membrane oxygenation (ECMO) may be applied. We report on the efficacy of V-V ECMO and invasive ventilation as initial advanced respiratory support in patients with COVID-19 and acute respiratory failure due to spontaneous PM. METHODS: This was a retrospective cohort study performed between March 2020 and January 2022. Enrolled patients had COVID-19 and acute respiratory failure due to spontaneous PM and were not invasively ventilated. Patients were treated in the intensive care unit (ICU) with invasive ventilation (invasive ventilation group) or V-V ECMO support (V-V ECMO group) as the main therapeutic option. The primary outcomes were mortality and ICU discharge at 90 days after ICU admission. RESULTS: Twenty-two patients were included in this study (invasive ventilation group: 13 [59%]; V-V ECMO group: 9 [41%]). The V-V ECMO strategy was significantly associated with lower mortality (hazard ratio [HR] 0.33 [95% CI 0.12-0.97], p = 0.04). Five (38%) patients in the V-V ECMO group were intubated and eight (89%) patients in the invasive ventilation group required V-V ECMO support within 30 days from ICU admission. Three (33%) patients in the V-V ECMO group were discharged from ICU within 90 days compared to one (8%) patient in the invasive ventilation group (HR 4.71 [95% CI 0.48-45.3], p = 0.18). CONCLUSIONS: Preliminary data suggest that V-V ECMO without invasive ventilation may improve survival in COVID-19-related acute respiratory failure due to spontaneous PM. The study's retrospective design and limited sample size underscore the necessity for additional investigation and warrant caution.

Lung Ultrasound Prediction Model for Acute Respiratory Distress Syndrome: A Multicenter Prospective Observational Study.

Rationale: Lung ultrasound (LUS) is a promising tool for diagnosis of acute respiratory distress syndrome (ARDS), but adequately sized studies with external validation are lacking. Objectives: To develop and validate a data-driven LUS score for diagnosis of ARDS and compare its performance with that of chest radiography (CXR). Methods: This multicenter prospective observational study included invasively ventilated ICU patients who were divided into a derivation cohort and a validation cohort. Three raters scored ARDS according to the Berlin criteria, resulting in a classification of "certain no ARDS," or "certain ARDS" when experts agreed or "uncertain ARDS" when evaluations conflicted. Uncertain cases were classified in a consensus meeting. Results of a 12-region LUS exam were used in a logistic regression model to develop the LUS-ARDS score. Measurements and Main Results: Three hundred twenty-four (16% certain ARDS) and 129 (34% certain ARDS) patients were included in the derivation cohort and the validation cohort, respectively. With an ARDS diagnosis by the expert panel as the reference test, the LUS-ARDS score, including the left and right LUS aeration scores and anterolateral pleural line abnormalities, had an area under the receiver operating characteristic (ROC) curve of 0.90 (95% confidence interval [CI], 0.85-0.95) in certain patients of the derivation cohort and 0.80 (95% CI, 0.72-0.87) in all patients of the validation cohort. Within patients who had imaging-gold standard chest computed tomography available, diagnostic accuracy of eight independent CXR readers followed the ROC curve of the LUS-ARDS score. Conclusions: The LUS-ARDS score can be used to accurately diagnose ARDS also after external validation. The LUS-ARDS score may be a useful adjunct to a diagnosis of ARDS after further validation, as it showed performance comparable with that of the current practice with experienced CXR readers but more objectifiable diagnostic accuracy at each cutoff.

Ratio of carbon dioxide veno-arterial difference to oxygen arterial-venous difference is not associated with lactate decrease after fluid bolus in critically ill patients with hyperlactatemia: results from a prospective observational study.

BACKGROUND: High ratio of the carbon dioxide veno-arterial difference to the oxygen arterial-venous difference (PvaCO2/CavO2) is associated with fluid bolus (FB) induced increase in oxygen consumption (VO2). This study investigated whether PvaCO2/CavO2 was associated with decreases in blood-lactate levels FB in critically ill patients with hyperlactatemia. METHODS: This prospective observational study examined adult patients in the intensive care unit (ICU) with lactate levels > 1.5 mmol/L who received FBs. Blood-lactate levels were measured before and after FB under unchanged metabolic, respiratory, and hemodynamic conditions. The primary outcome was blood-lactate levels after FB. Significant decreases in blood-lactate levels were considered as blood-lactate levels < 1.5 mmol/L or a decrease of more than 10% compared to baseline. RESULTS: The study enrolled 40 critically ill patients, and their median concentration of blood lactate was 2.6 [IQR:1.9 - 3.8] mmol/L. There were 27 (68%) patients with PvaCO2/CavO2 ≥ 1.4 mmHg/ml, and 10 of them had an increase in oxygen consumption (dVO2) ≥ 15% after FB, while 13 (32%) patients had PvaCO2/CavO2 < 1.4 mmHg/ml before FB, and none of them had dVO2 ≥ 15% after FB. FB increased the cardiac index in patients with high and low preinfusion PvaCO2/CavO2 (13.4% [IQR: 8.3 - 20.2] vs. 8.8% [IQR: 2.9 - 17.4], p = 0.34). Baseline PvaCO2/CavO2 was not found to be associated with a decrease in blood lactate after FB (OR: 0.88 [95% CI: 0.39 - 1.98], p = 0.76). A positive correlation was observed between changes in blood lactate and baseline PvaCO2/CavO2 (r = 0.35, p = 0.02). CONCLUSIONS: In critically ill patients with hyperlactatemia, PvaCO2/CavO2 before FB cannot be used to predict decreases in blood-lactate levels after FB. Increased PvaCO2/CavO2 is associated with less decrease in blood-lactate levels.

Biomarkers of sepsis: time for a reappraisal.

INTRODUCTION: Sepsis biomarkers can have important diagnostic, therapeutic, and prognostic functions. In a previous review, we identified 3370 references reporting on 178 different biomarkers related to sepsis. In the present review, we evaluate the progress in the research of sepsis biomarkers. METHODS: Using the same methodology as in our previous review, we searched the PubMed database from 2009 until September 2019 using the terms "Biomarker" AND "Sepsis." There were no restrictions by age or language, and all studies, clinical and experimental, were included. RESULTS: We retrieved a total of 5367 new references since our previous review. We identified 258 biomarkers, 80 of which were new compared to our previous list. The majority of biomarkers have been evaluated in fewer than 5 studies, with 81 (31%) being assessed in just a single study. Apart from studies of C-reactive protein (CRP) or procalcitonin (PCT), only 26 biomarkers have been assessed in clinical studies with more than 300 participants. Forty biomarkers have been compared to PCT and/or CRP for their diagnostic value; 9 were shown to have a better diagnostic value for sepsis than either or both of these biomarkers. Forty-four biomarkers have been evaluated for a role in answering a specific clinical question rather than for their general diagnostic or prognostic properties in sepsis. CONCLUSIONS: The number of biomarkers being identified is still increasing although at a slower rate than in the past. Most of the biomarkers have not been well-studied; in particular, the clinical role of these biomarkers needs to be better evaluated.

Long-term survival and quality of life in Jehovah's witnesses after cardiac surgery: a case control study.

BACKGROUND: We previously analyzed morbidity and mortality in Jehovah's Witnesses patients after cardiac surgery compared to control population patients. Patients who were Jehovah's Witnesses were operated in accordance with their philosophical convictions and in respect of their refusal of transfusions. We propose to assess long-term survival and quality of life in the patients of this preliminary study. METHODS: We contacted 31 adult Jehovah's Witnesses patients who underwent heart surgery at the Brugmann hospital between 1991 and 2012 and compared them to a control population of 62 patients that had no transfusion restriction, and matched them for sex, age at the time of intervention and the type of surgery performed. We compared long-term quality of life in both populations through the MacNew software, a validated instrument to assess quality of life of patients with cardiovascular disease. The long-term survival of patients was analyzed by Kaplan Meier curves. RESULTS: Long-term quality of life and survival do not appear different between the two groups. Patient evaluation by MacNew software shows comparable physical (p = 0.54), emotional (p = 0.12), social (p = 0.21) and global (p = 0.25) scores between the two populations. The analysis of the actuarial survival curves shows no differences in terms of long-term survival of these patients (p = 0.37). CONCLUSIONS: Cardiac surgery in Jehovah's Witnesses can be performed with identical long-term quality of life and survival compared to surgery without blood transfusion restriction, if one follows rigorous blood conserving strategies. TRIAL REGISTRATION: NCT03348072 . Retrospectively registered 16 November 2017.

Contegra versus pulmonary homograft for right ventricular outflow tract reconstruction in newborns.

OBJECTIVES: Pulmonary homografts are standard alternatives to right ventricular outflow tract reconstruction in congenital heart surgery. Unfortunately, shortage and conduit failure by early calcifications and shrinking are observed for small-sized homografts in younger patients. In neonates, Contegra® 12 mm (Medtronic Inc., Minneapolis, Minnesota, United States of America) could be a valuable alternative, but conflicting evidence exists. There is no published study considering only newborns with heterogeneous pathologies. We retrospectively compared the outcomes of these two conduits in this challenging population. METHODS: Patients who underwent a right ventricular outflow tract reconstruction between January 1992 and December 2014 at the Hôpital Universitaire des Enfants Reine Fabiola were included. We retrospectively collected and analysed demographic, echocardiographic, surgical, and follow-up data. RESULTS: Of the 53 newborns who benefited from a right ventricular outflow tract reconstruction during the considered period, 30 received a Contegra 12 mm (mean age 15 ± 8 days), and 23 a small (9-14 mm) pulmonary homograft (mean age 10 ± 7 days). Overall mortality was 16.6% with Contegra versus 17.4% in the pulmonary homograft group (p = 0.98 log-rank). Operative morbidity and early re-operation for conduit failure were not significantly different between the two groups. Mean follow-up in this study is 121 ± 74 months. Survival free from re-operation was not different between the two groups (p = 0.15). Multivariable analysis showed that weight and significant early gradient were factors associated with anticipated conduit failure. CONCLUSIONS: Contegra 12 mm is a valid alternative to small pulmonary homografts in a newborn patient population. TRIAL REGISTRATION: NCT03348397.

Sepsis is associated with altered cerebral microcirculation and tissue hypoxia in experimental peritonitis.

OBJECTIVE: Alterations in cerebral microvascular blood flow may develop during sepsis, but the consequences of these abnormalities on tissue oxygenation and metabolism are not well defined. We studied the evolution of microvascular blood flow, brain oxygen tension (PbO2), and metabolism in a clinically relevant animal model of septic shock. DESIGN: Prospective randomized animal study. SETTING: University hospital research laboratory. SUBJECTS: Fifteen invasively monitored and mechanically ventilated female sheep. INTERVENTIONS: The sheep were randomized to fecal peritonitis (n = 10) or a sham procedure (n = 5), and craniectomies were performed to enable evaluation of cerebral microvascular blood flow, PbO2, and metabolism. The microvascular network of the left frontal cortex was evaluated (at baseline, 6, 12, and 18 hr) using sidestream dark-field videomicroscopy. Using an off-line semiquantitative method, functional capillary density and the proportion of small perfused vessels were calculated. PbO2 was measured hourly by a parenchymal Clark electrode, and cerebral metabolism was assessed by the lactate/pyruvate ratio using brain microdialysis; both these systems were placed in the right frontal cortex. MEASUREMENT AND MAIN RESULTS: In septic animals, cerebral functional capillary density (from 3.1 ± 0.5 to 1.9 ± 0.4 n/mm, p < 0.001) and proportion of small perfused vessels (from 98% ± 2% to 84% ± 7%, p = 0.004) decreased over the 18-hour study period. Concomitantly, PbO2 decreased (61 ± 5 to 41 ± 7 mm Hg, p < 0.001) and lactate/pyruvate ratio increased (23 ± 5 to 36 ± 19, p < 0.001). At 18 hours, when shock was present, animals with a mean arterial pressure less than 65 mm Hg (n = 6) had similar functional capillary density, proportion of small perfused vessels, and PbO2 values but significantly higher lactate/pyruvate ratio (46 ± 18 vs 20 ± 4, p = 0.009) compared with animals with an mean arterial pressure of 65-70 mm Hg (n = 4). CONCLUSIONS: Impaired cerebral microcirculation during sepsis is associated with progressive impairment in PbO2 and brain metabolism. Development of severe hypotension was responsible for a further increase in anaerobic metabolism. These alterations may play an important role in the pathogenesis of brain dysfunction during sepsis.

Impact of infection on the prognosis of critically ill cirrhotic patients: results from a large worldwide study.

BACKGROUND: Infections are a leading cause of death in patients with advanced cirrhosis, but there are relatively few data on the epidemiology of infection in intensive care unit (ICU) patients with cirrhosis. AIMS: We used data from the Extended Prevalence of Infection in Intensive Care (EPIC) II 1-day point-prevalence study to better define the characteristics of infection in these patients. METHODS: We compared characteristics, including occurrence and types of infections in non-cirrhotic and cirrhotic patients who had not undergone liver transplantation. RESULTS: The EPIC II database includes 13,796 adult patients from 1265 ICUs: 410 of the patients had cirrhosis. The prevalence of infection was higher in cirrhotic than in non-cirrhotic patients (59 vs. 51%, P < 0.01). The lungs were the most common site of infection in all patients, but abdominal infections were more common in cirrhotic than in non-cirrhotic patients (30 vs. 19%, P < 0.01). Infected cirrhotic patients more often had Gram-positive (56 vs. 47%, P < 0.05) isolates than did infected non-cirrhotic patients. Methicillin-resistant Staphylococcus aureus (MRSA) was more frequent in cirrhotic patients. The hospital mortality rate of cirrhotic patients was 42%, compared to 24% in the non-cirrhotic population (P < 0.001). Severe sepsis and septic shock were associated with higher in-hospital mortality rates in cirrhotic than in non-cirrhotic patients (41% and 71% vs. 30% and 49%, respectively, P < 0.05). CONCLUSIONS: Infection is more common in cirrhotic than in non-cirrhotic ICU patients and more commonly caused by Gram-positive organisms, including MRSA. Infection in patients with cirrhosis was associated with higher mortality rates than in non-cirrhotic patients.

Transcranial Doppler to assess sepsis-associated encephalopathy in critically ill patients.

BACKGROUND: Transcranial Doppler can detect cerebral perfusion alteration in septic patients. We correlate static Transcranial Doppler findings with clinical signs of sepsis-associated encephalopathy. METHODS: Forty septic patients were examined with Transcranial Doppler on the first and third day of sepsis diagnosis. The pulsatility index (PI) and cerebral blood flow index (CBFi) were calculated by blood velocity in the middle cerebral artery (cm/sec). Patients underwent a daily cognitive assessment with the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU) test. RESULTS: Twenty-one patients (55%) were found to present confusion. The majority of the patients presented a PI > 1.1 (76%). PI on the first day (but not the third day) could predict a positive CAM-ICU test in septic patients (PI cut-off: 1.3, AUC: 0.905, p < 0.01, sensitivity: 95%, specificity: 88%, AUC: 0.618, p = 0.24). Multivariable analysis showed that PI on the first day is related to a positive CAM-ICU test independent of age and APACHE II score (OR: 5.6, 95% CI: 1.1-29, p = 0.03). A decrease of the PI on the third day was observed in the group that presented initially high PI (>1.3) (2.2 ± 0.71 vs. 1.81 ± 0.64; p = 0.02). On the other hand, an increase in PI was observed in the other patients (1.01 ± 0.15 vs. 1.58 ± 0.57; p < 0.01). On only the first day, the mean blood velocity in the middle cerebral artery and CBFi were found to be lower in those patients with a high initial PI (36 ± 21 vs. 62 ± 28 cm/sec; p < 0.01, 328 ± 101 vs. 581 ± 108; p < 0.01, respectively). CONCLUSIONS: Cerebral perfusion disturbance observed with Transcranial Doppler could explain clinical symptoms of sepsis-associated encephalopathy.

Inflammatory biomarker-based clinical practice in patients with pneumonia: A systematic review of randomized controlled trials.

Objectives: Biomarker-based clinical practice is currently gaining ground and increasingly affects decision making. A variety of biomarkers have been studied through the years and some of them have already an established role in modern medicine, such as procalcitonin (PCT) which has been proposed to reduce antibiotic exposure. We purposed to systematically review all biomarkers examined for guiding the clinical practice in patients with pneumonia. METHODS: A systematic review on PubMed was performed on April 2023 by two independent researchers using the PRISMA guidelines. Randomized trials which enrolled patients with pneumonia and compared biomarker-guided strategies to standard of care were included. RESULTS: 1242 studies were recorded, from whom 16 were eligible for this study. 14 studies investigated PCT as a biomarker. From these, 8 studies reported on community acquired pneumonia (CAP), 2 on ventilator associated pneumonia (VAP), 1 on aspiration pneumonia, 1 on hospital acquired pneumonia (HAP) and 2 on exacerbation of chronic obstructive pulmonary disease (ECOPD). There was 1 study, referred to VAP, that investigated interleukin-1ß (IL-1ß) and interleukin-8 (IL-8) and 1 study that reported the role of C-reactive protein (CRP) in ECOPD. In a total of 4751 patients in 15 studies, the biomarker-based approach did not lead to increased mortality [OR: 0.998 (95%CI: 0.74-1.34, p value: 0.991). I2:19%]. Among different types of pneumonia and time-points of assessment, biomarker-guided practice appeared to improve antibiotic-related outcomes, such as rate of antibiotic prescription, duration of antibiotic therapy and rate of antibiotic exposure, while 5 studies reported a possible decrease in antibiotic-related adverse effects. Biomarker-guided practice did not seem to lead in an increase in other adverse outcomes such as need for hospitalization and duration of hospitalization. However, the included studies have high risk of bias mainly due to improper blinding of participants/personnel and outcome assessors. CONCLUSION: Biomarker-guided clinical practice improves provided healthcare, in terms of reduced antibiotic consumption with no inferiority to mortality, relapses and exacerbations in patients with different types of pneumonia. Thus, such approaches should be further evaluated to achieve personalized medicine.

Evaluating the efficacy of a standardized 4 mL/kg fluid bolus technique in critically ill patients with elevated PvaCO2: secondary analysis of two prospective studies.

Background: Limiting the fluid bolus (FB) volume may attenuate side effects, including hemodilution and increased filling pressures, but it may also reduce hemodynamic responsiveness. The minimum volume to create hemodynamic effects is considered to be 4 mL/kg. In critically ill patients, the hemodynamic effects of FB with this volume have not been adequately investigated and compared to higher quantities. We hypothesized that a standardized FB approach using 4 mL/kg has comparable hemodynamic and metabolic effects to the common practice of physician-determined FB in critically ill patients. Methods: We conducted post hoc analysis of two trials in non-selected critically ill patients with central venous-to-arterial CO2 tension (PvaCO2) >6 mmHg and no acute bleeding. All patients received crystalloids either at a physician-determined volume and rate or at 4 mL/kg pump-administered at 1.2 L/h. Cardiac index (CI) was calculated with transthoracic echocardiogram, and arterial and venous blood gas samples were assessed before and after FB. Endpoints were changes in CI and oxygen delivery (DO2) >15%. Results: A total of 47 patients were eligible for the study, 15 of whom received physician-determined FB and 32 of whom received standardized FB. Patients in the physician-determined FB group received 16 (12-19) mL/kg at a fluid rate of 1.5 (1.5-1.9) L/h, compared to 4.1 (3.7-4.4) mL/kg at a fluid rate of 1.2 (1.2-1.2) L/h (p < 0.01) in the standardized FB group. The difference in CI elevations between the two groups was not statistically significant (8.8% [-0.1-19.9%] vs. 8.4% [0.3-23.2%], p = 0.76). Compared to physician-determined FB, the standardized FB technique had similar probabilities of increasing CI or DO2 by >15% (odds ratios: 1.3 [95% CI: 0.37-5.18], p = 0.66 and 1.83 [95% CI: 0.49-7.85], p = 0.38). Conclusion: A standardized FB protocol (4 mL/kg at 1.2 L/h) effectively reduced the volume of fluid administered to critically ill patients without compromising hemodynamic or metabolic effects.

Personalized mechanical ventilation guided by ultrasound in patients with acute respiratory distress syndrome (PEGASUS): study protocol for an international randomized clinical trial.

BACKGROUND: Acute respiratory distress syndrome (ARDS) is a frequent cause of hypoxemic respiratory failure with a mortality rate of approximately 30%. Identifying ARDS subphenotypes based on "focal" or "non-focal" lung morphology has the potential to better target mechanical ventilation strategies of individual patients. However, classifying morphology through chest radiography or computed tomography is either inaccurate or impractical. Lung ultrasound (LUS) is a non-invasive bedside tool that can accurately distinguish "focal" from "non-focal" lung morphology. We hypothesize that LUS-guided personalized mechanical ventilation in ARDS patients leads to a reduction in 90-day mortality compared to conventional mechanical ventilation. METHODS: The Personalized Mechanical Ventilation Guided by UltraSound in Patients with Acute Respiratory Distress Syndrome (PEGASUS) study is an investigator-initiated, international, randomized clinical trial (RCT) that plans to enroll 538 invasively ventilated adult intensive care unit (ICU) patients with moderate to severe ARDS. Eligible patients will receive a LUS exam to classify lung morphology as "focal" or "non-focal". Thereafter, patients will be randomized within 12 h after ARDS diagnosis to receive standard care or personalized ventilation where the ventilation strategy is adjusted to the morphology subphenotype, i.e., higher positive end-expiratory pressure (PEEP) and recruitment maneuvers for "non-focal" ARDS and lower PEEP and prone positioning for "focal" ARDS. The primary endpoint is all-cause mortality at day 90. Secondary outcomes are mortality at day 28, ventilator-free days at day 28, ICU length of stay, ICU mortality, hospital length of stay, hospital mortality, and number of complications (ventilator-associated pneumonia, pneumothorax, and need for rescue therapy). After a pilot phase of 80 patients, the correct interpretation of LUS images and correct application of the intervention within the safe limits of mechanical ventilation will be evaluated. DISCUSSION: PEGASUS is the first RCT that compares LUS-guided personalized mechanical ventilation with conventional ventilation in invasively ventilated patients with moderate and severe ARDS. If this study demonstrates that personalized ventilation guided by LUS can improve the outcomes of ARDS patients, it has the potential to shift the existing one-size-fits-all ventilation strategy towards a more individualized approach. TRIAL REGISTRATION: The PEGASUS trial was registered before the inclusion of the first patient, https://clinicaltrials.gov/ (ID: NCT05492344).

N-acetylcysteine efficacy in patients hospitalized with COVID-19 pneumonia: a systematic review and meta-analysis.

BACKGROUND: N-acetylcysteine (NAC) is a mucolytic agents with anti-inflammatory properties that has been suggested as an adjunctive therapy in patients with COVID-19 pneumonia. OBJECTIVES: We conducted a systematic review and meta-analysis to evaluate available evidence on the possible beneficial effects of NAC on SARS-CoV-2 infection. METHODS: In September 2022, we conducted a comprehensive search on Pubmed/Medline and Embase on randomized controlled trials (RCTs) and observational studies on NAC in patients with COVID-19 pneumonia. Study selection, data extraction and risk of bias assessment was performed by two independent authors. RCTs and observational studies were analyzed separately. RESULTS: We included 3 RCTs and 5 non-randomized studies on the efficacy of NAC in patients with COVID-19, enrolling 315 and 20826 patients respectively. Regarding in-hospital mortality, the summary effect of all RCTs was OR: 0.85 (95% CI: 0.43 to 1.67, I2=0%) and for non-randomized studies OR: 1.02 (95% CI: 0.47 to 2.23, I2=91%). Need for ICU admission was only reported by 1 RCT (OR: 0.86, 95% CI:0.44-1.69, p=0.66), while all included RCTs reported need for invasive ventilation (OR:0.91, 95% CI:0.54 to 1.53, I2=0). Risk of bias was low for all included RCTs, but certainty of evidence was very low for all outcomes due to serious imprecision and indirectness. CONCLUSION: The certainty of evidence in the included studies was very low, thus recommendations for clinical practice cannot be yet made. For all hard clinical outcomes point estimates in RCTs are close to the line of no effect, while observational studies have a high degree of heterogeneity with some of them suggesting favorable results in patients receiving NAC. More research is warranted to insure that NAC is both effective and safe in patients with COVID-19 pneumonia.

Impact of Bacterial Infections on COVID-19 Patients: Is Timing Important?

BACKGROUND: Along with important factors that worsen the clinical outcome of COVID-19, it has been described that bacterial infections among patients positive for a SARS-CoV-2 infection can play a dramatic role in the disease process. Co-infections or community-acquired infections are recognized within the first 48 h after the admission of patients. Superinfections occur at least 48 h after admission and are considered to contribute to a worse prognosis. Microbiologic parameters differentiate infections that happen after the fifth day of hospitalization from those appearing earlier. Specifically, after the fifth day, the detection of resistant bacteria increases and difficult microorganisms emerge. OBJECTIVES: The aim of the study was to evaluate the impact of bacterial infections in patients with COVID-19 on the length of the hospital stay and mortality. METHODS: A total of 177 patients hospitalized due to COVID-19 pneumonia were consecutively sampled during the third and fourth wave of the pandemic at a University Hospital in Greece. A confirmed bacterial infection was defined as positive blood, urinary, bronchoalveolar lavage (BAL) or any other infected body fluid. Patients with confirmed infections were further divided into subgroups according to the time from admission to the positive culture result. RESULTS: When comparing the groups of patients, those with a confirmed infection had increased odds of death (odds ratio: 3.634; CI 95%: 1.795-7.358; p < 0.001) and a longer length of hospital stay (median 13 vs. 7 days). A late onset of infection was the most common finding in our cohort and was an independent risk factor for in-hospital death. Mortality and the length of hospital stay significantly differed between the subgroups. CONCLUSION: In this case series, microbial infections were an independent risk factor for a worse outcome among patients with COVID-19. Further, a correlation between the onset of infection and a negative outcome in terms of non-infected, community-acquired, early hospital-acquired and late hospital-acquired infections was identified. Late hospital-acquired infections increased the mortality of COVID-19 patients whilst superinfections were responsible for an extended length of hospital stay.

A Literature Review of Pathophysiology, Clinical Manifestations, Medications and Optimal Dosage, Outpatient, and Post-hospitalization Use of Anticoagulation in COVID-19 Patients.

Since severe acute respiratory syndrome coronavirus 2 led to a world pandemic, extensive research has been conducted to identify its characteristics and form an appropriate management plan. One recognized complication of COVID-19 is coagulation defects that can lead to thromboembolic events. We have reviewed the literature to summarize and present the latest research about the pathophysiology, clinical manifestations, anticoagulation use and appropriate dose in COVID-19 patients, as well as the effect of anticoagulation in outpatient and post-hospital settings. The pathophysiology of coagulation abnormalities in COVID-19 is not fully understood yet, but multiple mechanisms appear to be involved, such as a direct viral attack, hyperinflammation, increased immune response, blood stasis, and endothelial injury. Clinical manifestations are mainly venous thromboembolism (deep vein thrombosis and pulmonary embolism), arterial thromboembolism, ischemic stroke, central venous sinus thrombosis, and central retinal vein occlusion. Anticoagulation is widely used in hospitalized patients with COVID-19, unless it is contraindicated. Heparinoid is the main anticoagulant used. However, the appropriate dosage is still debated as research is trying to find a balance between benefits and risks. In outpatients, it appears that anticoagulation has no benefit in contrast to post-hospitalization use, where benefit could be observed in severely affected patients. We concluded that thromboprophylaxis should be used in treating hospitalized COVID-19 patients, but the dosage is still a matter of debate. More research needs to be done on outpatient and post-hospitalized patients to derive accurate conclusions.

Lung Ultrasound to Determine the Effect of Lower vs. Higher PEEP on Lung Aeration in Patients without ARDS-A Substudy of a Randomized Clinical Trial.

BACKGROUND: Ventilation with lower positive end-expiratory pressure (PEEP) may cause loss of lung aeration in critically ill invasively ventilated patients. This study investigated whether a systematic lung ultrasound (LUS) scoring system can detect such changes in lung aeration in a study comparing lower versus higher PEEP in invasively ventilated patients without acute respiratory distress syndrome (ARDS). METHODS: Single center substudy of a national, multicenter, randomized clinical trial comparing lower versus higher PEEP ventilation strategy. Fifty-seven patients underwent a systematic 12-region LUS examination within 12 h and between 24 to 48 h after start of invasive ventilation, according to randomization. The primary endpoint was a change in the global LUS aeration score, where a higher value indicates a greater impairment in lung aeration. RESULTS: Thirty-three and twenty-four patients received ventilation with lower PEEP (median PEEP 1 (0-5) cm H2O) or higher PEEP (median PEEP 8 (8-8) cm H2O), respectively. Median global LUS aeration scores within 12 h and between 24 and 48 h were 8 (4 to 14) and 9 (4 to 12) (difference 1 (-2 to 3)) in the lower PEEP group, and 7 (2-11) and 6 (1-12) (difference 0 (-2 to 3)) in the higher PEEP group. Neither differences in changes over time nor differences in absolute scores reached statistical significance. CONCLUSIONS: In this substudy of a randomized clinical trial comparing lower PEEP versus higher PEEP in patients without ARDS, LUS was unable to detect changes in lung aeration.

The changing pattern of acute respiratory distress syndrome over time: a comparison of two periods.

This study aimed to assess whether patterns and outcomes of acute respiratory distress syndrome (ARDS) have changed due to improvements in mechanical ventilation techniques and support of critically ill patients, by comparing patients from two different periods in the same hospital. We reviewed data from all patients with a diagnosis of ARDS (according to American-European Consensus Conference criteria) who were treated in our multidisciplinary department of intensive care (Erasme Hospital, Brussels) between January 2006 and April 2009 (group B, n=210) and compared them with our previously reported data (January 1993 to February 1995) (group A, n=129). The prevalence of ARDS has decreased (from 2.5% in group A to 1.7% in group B, p<0.001). ARDS patients are now older and sepsis-related ARDS is more common. Multiple transfusion and trauma are less common causes of ARDS than in the past. Intensive care unit length of stay among survivors is shorter (13 ± 9 versus 17 ± 17 days, p=0.025), and there was a trend to lower mortality rates in the more recent cohort (46% versus 52%, p=0.158). Multiple organ failure (MOF) was the most common cause of death in both periods. The pattern of ARDS has changed over time in our department. Patients with ARDS are now older and more severely ill. Sepsis-related ARDS is more frequent whereas trauma-related and/or transfusion-related ARDS has decreased. MOF still represents the most frequent cause of death.

Soluble urokinase plasminogen activator receptor (suPAR) in the emergency department: An update.

Background: The biomarker soluble urokinase plasminogen activator receptor (suPAR) is an indicator of inflammation which is increased in a variety of chronic and acute disease states. Its most promising application in the emergency setting is to aid in the prognostic stratification of patients by identifying those at high risk of deterioration. This is a narrative review of studies evaluating the use of suPAR. Methods: We conducted a Medline search for studies on the use of suPAR in patients acutely admitted to the emergency department. Results: 25 original studies were included in the review. suPAR as a marker of inflammation has been used alone or combined to other inflammatory biomarkers in the assessment of patients suffering from various acute and chronic diseases in an emergency setting. As it is non-specific, it may increase in infectious disease, malignancy or acute coronary syndromes among other conditions, but quantitative suPAR levels correlate with disease severity. It may be useful for the identification of high risk patients regardless of underlying pathology. Conclusion: As the ideal biomarker in the emergency setting has not been identified yet, suPAR may be a promising addition to the established biomarkers for the initial assessment of patients in this setting. Additional research is necessary to evaluate the usefulness of suPAR guided management algorithms.

Abnormal Right Ventricular Myocardial Performance Index Is Not Associated With Outcomes in Invasively Ventilated Intensive Care Unit Patients Without Acute Respiratory Distress Syndrome-Post hoc Analysis of Two RCTs.

Background: The objective of the study was to determine the association between right ventricular (RV) myocardial performance index (MPI) and successful liberation from the ventilator and death within 28 days. Methods: Post hoc analysis of 2 ventilation studies in invasively ventilated patients not having ARDS. RV-MPI was collected through transthoracic echocardiography within 24-48 h from the start of invasive ventilation according to the study protocols. RV-MPI ≤ 0.54 was considered normal. The primary endpoint was successful liberation from the ventilator < 28 days; the secondary endpoint was 28-day mortality. Results: A total of 81 patients underwent transthoracic echocardiography at median 30 (24-42) h after the start of ventilation-in 73 (90%) patients, the RV-MPI could be collected. A total of 56 (77%) patients were successfully liberated from the ventilator < 28 days; A total of 22 (30%) patients had died before or at day 28. A total of 18 (25%) patients had an abnormal RV-MPI. RV-MPI was neither associated with successful liberation from the ventilator within 28 days [HR, 2.2 (95% CI 0.47-10.6); p = 0.31] nor with 28-day mortality [HR, 1.56 (95% CI 0.07-34.27); p = 0.7]. Conclusion: In invasively ventilated critically ill patients without ARDS, an abnormal RV-MPI indicative of RV dysfunction was not associated with time to liberation from invasive ventilation.

Prone Positioning Decreases Inhomogeneity and Improves Dorsal Compliance in Invasively Ventilated Spontaneously Breathing COVID-19 Patients-A Study Using Electrical Impedance Tomography.

BACKGROUND: We studied prone positioning effects on lung aeration in spontaneously breathing invasively ventilated patients with coronavirus disease 2019 (COVID-19). METHODS: changes in lung aeration were studied prospectively by electrical impedance tomography (EIT) from before to after placing the patient prone, and back to supine. Mixed effect models with a random intercept and only fixed effects were used to evaluate changes in lung aeration. RESULTS: fifteen spontaneously breathing invasively ventilated patients were enrolled, and remained prone for a median of 19 [17 to 21] hours. At 16 h the global inhomogeneity index was lower. At 2 h, there were neither changes in dorsal nor in ventral compliance; after 16 h, only dorsal compliance (ßFe +18.9 [95% Confidence interval (CI): 9.1 to 28.8]) and dorsal end-expiratory lung impedance (EELI) were increased (ßFe, +252 [95% CI: 13 to 496]); at 2 and 16 h, dorsal silent spaces was unchanged (ßFe, -4.6 [95% CI: -12.3 to +3.2]). The observed changes induced by prone positioning disappeared after turning patients back to supine. CONCLUSIONS: in this cohort of spontaneously breathing invasively ventilated COVID-19 patients, prone positioning decreased inhomogeneity, increased lung volumes, and improved dorsal compliance.