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The article discusses the results of a study which analyzes the use of end-inspiratory occlusion method to measure the inspiratory resistance of adult endothracheal tubes (ETT). According to the authors, the resistive behavior of ETT was measured by plotting inspiratory resistance over inspiratory flow and determining Rohrer's coefficients of linear and nonlinear resistance. They add that the determination of ETT size may assist clinicians in identifying ETT obstruction and addressing problems related to weaning.

The article discusses the study that determines whether incorrect antibiotic choice against the particular strain of pneumococcus can affect clinical outcome. The study identified 2 randomized trials and 4 prospective studies of amoxicillin-clavulanate, penicillin, cefuroxime, ceftriaxone and cefotaxime. It is known that mortality in the patients was not different for patients treated with an antibiotic that was ineffective against the pneumococcal strain, despite the high mortality rates in these studies. As observed, initial choice of antibiotic for pneumococcal pneumonia is not important because patients get better even when the bacteria are resistant to the antibiotic.

Acute hypoxemic respiratory failure (AHRF) is defined as acute and progressive, and patients are at a greater risk of developing acute respiratory distress syndrome (ARDS). Until now, most studies have focused on prognostic and diagnostic biomarkers in ARDS. Since there is evidence supporting a connection between dysregulated coagulant and fibrinolytic pathways in ARDS progression, it is plausible that this dysregulation also exists in AHRF. The aim of this study was to explore whether levels of soluble endothelial protein C receptor (sEPCR) and plasminogen differentiate patients admitted to the emergency department (ED) with AHRF. sEPCR and plasminogen levels were measured in 130 AHRF patients upon ED presentation by ELISA. Our results demonstrated that patients presenting to the ED with AHRF had elevated levels of sEPCR and plasminogen. It seems that dysregulation of coagulation and fibrinolysis occur in the early stages of respiratory failure requiring hospitalisation. Further research is needed to fully comprehend the contribution of sEPCR and plasminogen in AHRF.

Background: Sepsis is a heterogeneous syndrome, and the identification of clinical subphenotypes is essential. Although organ dysfunction is a defining element of sepsis, subphenotypes of differential trajectory are not well studied. We sought to identify distinct Sequential Organ Failure Assessment (SOFA) score trajectory-based subphenotypes in sepsis., Methods: We created 72-h SOFA score trajectories in patients with sepsis from four diverse intensive care unit (ICU) cohorts. We then used dynamic time warping (DTW) to compute heterogeneous SOFA trajectory similarities and hierarchical agglomerative clustering (HAC) to identify trajectory-based subphenotypes. Patient characteristics were compared between subphenotypes and a random forest model was developed to predict subphenotype membership at 6 and 24 h after being admitted to the ICU. The model was tested on three validation cohorts. Sensitivity analyses were performed with alternative clustering methodologies., Results: A total of 4678, 3665, 12,282, and 4804 unique sepsis patients were included in development and three validation cohorts, respectively. Four subphenotypes were identified in the development cohort: Rapidly Worsening (n = 612, 13.1%), Delayed Worsening (n = 960, 20.5%), Rapidly Improving (n = 1932, 41.3%), and Delayed Improving (n = 1174, 25.1%). Baseline characteristics, including the pattern of organ dysfunction, varied between subphenotypes. Rapidly Worsening was defined by a higher comorbidity burden, acidosis, and visceral organ dysfunction. Rapidly Improving was defined by vasopressor use without acidosis. Outcomes differed across the subphenotypes, Rapidly Worsening had the highest in-hospital mortality (28.3%, P-value < 0.001), despite a lower SOFA (mean: 4.5) at ICU admission compared to Rapidly Improving (mortality:5.5%, mean SOFA: 5.5). An overall prediction accuracy of 0.78 (95% CI, [0.77, 0.8]) was obtained at 6 h after ICU admission, which increased to 0.87 (95% CI, [0.86, 0.88]) at 24 h. Similar subphenotypes were replicated in three validation cohorts. The majority of patients with sepsis have an improving phenotype with a lower mortality risk; however, they make up over 20% of all deaths due to their larger numbers., Conclusions: Four novel, clinically-defined, trajectory-based sepsis subphenotypes were identified and validated. Identifying trajectory-based subphenotypes has immediate implications for the powering and predictive enrichment of clinical trials. Understanding the pathophysiology of these differential trajectories may reveal unanticipated therapeutic targets and identify more precise populations and endpoints for clinical trials., (© 2022. The Author(s).)

Since changes in pharmacological treatments for severely ill patients with coronavirus disease 2019 have been incorporated into clinical practice, both by their use (corticosteroids and remdesivir) and by stopping them (e.g., hydroxychloroquine), we sought to compare the rate of intubation and mortality of intubated patients in our ICUs between the first and second waves of the pandemic., Design: Single-center, observational., Setting: Four coronavirus disease 2019 designated ICUs at an urban Greek teaching hospital., Patients: All adult patients with coronavirus disease 2019 consecutively admitted to ICU during the first ( n = 50) and second ( n = 212) waves of the pandemic., Interventions: None., Measurements and Main Results: The percentage of intubated ICU patients dropped from 82% during the first wave to 66% during the second wave ( p = 0.042). However, the absolute number of intubated ICU patients was lower during the first than the second wave (41 vs 140 patients). ICU or hospital mortality of intubated patients increased from 39% during the first wave to 60% during the second wave ( p = 0.028). The binary logistic regression for hospital mortality as the dependent variable in intubated patients and covariates the age, Acute Physiology and Chronic Health Evaluation II score, cardiovascular comorbidity, lactate, positive end-expiratory pressure, Sequential Organ Failure Assessment score, and wave, distinguished only Acute Physiology and Chronic Health Evaluation II (odds ratio, 1.40 with 95% CI, 1.14-1.72; p = 0.001) as the sole independent predictor of hospital mortality., Conclusions: Pharmacological adaptations and other measures may have led to fewer intubations over time. However, these changes do not seem to be translated into improved outcomes of intubated patients. Perhaps the same change in the use of drugs and protocols that could cause fewer intubations of ICU patients might be a reason of increased mortality in those patients who are eventually intubated. Furthermore, the relative staff inexperience and overall increase in patients' comorbidities during the second wave could have contributed to increased Acute Physiology and Chronic Health Evaluation II score and mortality of intubated patients., Competing Interests: The authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2021 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine.)

Although coagulation disorders and immune/inflammatory response have been associated with the final outcome of patients with sepsis, their link with thetemporaryclinical deterioration or improvement of patients is unknown. We aimed to investigate this link. We prospectively included consecutive patients admitted to the intensive care unit (ICU) with a suspected diagnosis of infection and evaluated within the first 24 h from admission. Blood levels of many cytokines and inflammatory and coagulation factors were measured and their predictive value was assessed by calculating the Area Under the Receiver Operating Characteristic (AUROC) curves. Patients ( n = 102) were allocated in five groups, i.e., sepsis ( n = 14), severe sepsis ( n = 17), septic shock ( n = 28), Systemic Inflammatory Response Syndrome (SIRS) without infection ( n = 17), and trauma/surgery without SIRS or infection ( n = 26). In septic shock, coagulation factors FVII and FIX and Protein C had AUROCs 0.67-0.78. In severe sepsis, Antithrombin III, Protein C, C-reactive protein, Procalcitonin and Thrombopoietin had AUROCs 0.73-0.75. In sepsis, Tumor Necrosis Factor a, and Interleukins 1β and 10 had AUROCs 0.66-0.72. In patients admitted to the ICU with a suspected diagnosis of infection, coagulation factors and inhibitors, as well as cytokine and inflammatory marker levels, have substantial predictive value in distinct groups of septic patients.

Background: According to the literature, 20-30% of intubated patients are difficult to wean off mechanical ventilation and have a prolonged intensive care unit (ICU) stay with detrimental effects on muscle strength, functional ability and quality of life. Inspiratory muscle training (IMT) via a threshold device has been proposed as an effective exercise for minimising the effects of mechanical ventilation on respiratory muscles of critically ill patients with prolonged weaning. In addition, high-flow nasal cannula (HFNC) oxygen has been proved to provide efficient support for both high- and low-risk patients after extubation, thus preventing re-intubation., Material and Methods: A randomised controlled trial was designed to assess the efficacy of combining IMT and HFNC as therapeutic strategies for patients with high risk for weaning failure. Once patients with prognostic factors of difficult weaning are awake, ventilated with support settings and cooperative, they will be randomised to one of the two following study groups: intervention group (IMT and HFNC) and control group (IMT and Venturi mask). IMT will start as soon as possible. Each allocated oxygen delivery device will be applied immediately after extubation. IMT intervention will continue until patients' discharge from ICU. The primary outcome is the rate of weaning failure. Secondary outcomes are maximal inspiratory and expiratory strength, endurance of respiratory muscles, global muscle strength, functional ability and quality of life along with duration of ventilation (days) and ICU and hospital length of stay., Conclusion: The present study could significantly contribute to knowledge of how best to treat patients with difficult weaning and high risk of re-intubation., Competing Interests: Conflict of interest: I. Patsaki has nothing to disclose. Conflict of interest: A. Christakou has nothing to disclose. Conflict of interest: E. Papadopoulos has nothing to disclose. Conflict of interest: M. Katartzi has nothing to disclose. Conflict of interest: A. Kouvarakos has nothing to disclose. Conflict of interest: I. Siempos has nothing to disclose. Conflict of interest: D. Tsimouris has nothing to disclose. Conflict of interest: A. Skoura has nothing to disclose. Conflict of interest: A. Xatzimina has nothing to disclose. Conflict of interest: S. Malachias has nothing to disclose. Conflict of interest: N. Koulouris has nothing to disclose. Conflict of interest: E. Grammatopoulou has nothing to disclose. Conflict of interest: S. Zakynthinos has nothing to disclose. Conflict of interest: E. Ischaki has nothing to disclose., (Copyright ©ERS 2020.)

Background: Mortality from severe acute respiratory distress syndrome exceeds 40% and there is no available pharmacologic treatment. Mechanical ventilation contributes to lung dysfunction and mortality by causing ventilator-induced lung injury. We explored the utility of simvastatin in a mouse model of severe ventilator-induced lung injury., Methods: Male C57BL6 mice (n = 7/group) were pretreated with simvastatin or saline and received protective (8 mL/kg) or injurious (25 mL/kg) ventilation for four hours. Three doses of simvastatin (20 mg/kg) or saline were injected intraperitoneally on days -2, -1 and 0 of the experiment. Lung mechanics, (respiratory system elastance, tissue damping and airway resistance), were evaluated by forced oscillation technique, while respiratory system compliance was measured with quasi-static pressure-volume curves. A pathologist blinded to treatment allocation scored hematoxylin-eosin-stained lung sections for the presence of lung injury. Pulmonary endothelial dysfunction was ascertained by bronchoalveolar lavage protein content and lung tissue expression of endothelial junctional protein Vascular Endothelial cadherin by immunoblotting. To assess the inflammatory response in the lung, we determined bronchoalveolar lavage fluid total cell content and neutrophil fraction by microscopy and staining in addition to Matrix-Metalloprotease-9 by ELISA. For the systemic response, we obtained plasma levels of Tumor Necrosis Factor-α, Interleukin-6 and Matrix-Metalloprotease-9 by ELISA. Statistical hypothesis testing was undertaken using one-way analysis of variance and Tukey's post hoc tests., Results: Ventilation with high tidal volume (HVt) resulted in significantly increased lung elastance by 3-fold and decreased lung compliance by 45% compared to low tidal volume (LVt) but simvastatin abrogated lung mechanical alterations of HVt. Histologic lung injury score increased four-fold by HVt but not in simvastatin-pretreated mice. Lavage pleocytosis and neutrophilia were induced by HVt but were significantly attenuated by simvastatin. Microvascular protein permeability increase 20-fold by injurious ventilation but only 4-fold with simvastatin. There was a 3-fold increase in plasma Tumor Necrosis Factor-α, a 7-fold increase in plasma Interleukin-6 and a 20-fold increase in lavage fluid Matrix-Metalloprotease-9 by HVt but simvastatin reduced these levels to control. Lung tissue vascular endothelial cadherin expression was significantly reduced by injurious ventilation but remained preserved by simvastatin., Conclusion: High-dose simvastatin prevents experimental hyperinflation lung injury by angioprotective and anti-inflammatory effects.

This is a historical article about Ancient Greek literature from mythological times until the first centuries AD with regard to the female breast. We endeavoured to collect several elegant narratives on the topic as well as to explore the knowledge of Ancient Greek doctors on the role, physiology and pathology of breast and the treatment of its diseases. We identified such descriptions in myths regarding Amazons, Hercules, Zeus, Hera and Amaltheia. Furthermore, descriptions on the topic were also found in the work of Hippocrates, Aristoteles, Soranos, Alexander of Aphrodisias, Celsus, Archigenis, Leonides, Galen and Oribasius. We may conclude that some of today's medical knowledge or practice regarding the breast was also known in the historical period.

We have assessed the evidence that closed tracheal suction systems (TSS) prevent ventilator-associated pneumonia (VAP), using a meta-analysis of randomized controlled trials (RCTs). We searched PubMed and Cochrane databases to identify RCTs that compared closed with open TSS for the management of mechanically ventilated (MV) patients. Nine RCTs were included in the meta-analysis. There was no difference in the incidence of VAP between patients managed with closed and open TSS [odds ratio (OR)=0.96, 95% confidence intervals (CI) 0.72-1.28]. There was no heterogeneity among the eligible trials (I2=0, 95% CI 0-0.65). The compared groups did not differ with respect to mortality (OR=1.04, 95% CI 0.78-1.39) or intensive care unit (ICU) length of stay [two RCTs: 12.3 (sd 1.1) vs 11.5 (1.4) days and 15.6 (13.4) vs 19.9 (16.7) days]. Suctioning with closed systems was associated with longer MV duration (weighted mean differences: 0.65 days, 95% CI 0.28-1.03) and higher colonization of the respiratory tract (OR=2.88, 95% CI 1.50-5.52) than open TSS. The available evidence suggests that closed as opposed to open TSS usage did not provide any benefit on VAP incidence, mortality, or ICU stay of MV patients.