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BACKGROUND: Streptococcus pneumoniae is the most common bacterial cause of community acquired pneumonia and the acute respiratory distress syndrome (ARDS). Some clinical trials have demonstrated a beneficial effect of corticosteroid therapy in community acquired pneumonia, COVID-19, and ARDS, but the mechanisms of this benefit remain unclear. The primary objective of this study was to investigate the effects of corticosteroids on the pulmonary biology of pneumococcal pneumonia in a mouse model. A secondary objective was to identify shared transcriptomic features of pneumococcal pneumonia and steroid treatment in the mouse model and clinical samples. METHODS: We carried out comprehensive physiologic, biochemical, and histological analyses in mice to identify the mechanisms of lung injury in Streptococcus pneumoniae with and without adjunctive steroid therapy. We also studied lower respiratory tract gene expression from a cohort of 15 mechanically ventilated patients (10 with Streptococcus pneumoniae and 5 controls) to compare with the transcriptional studies in the mice. RESULTS: In mice with pneumonia, dexamethasone in combination with ceftriaxone reduced (1) pulmonary edema formation, (2) alveolar protein permeability, (3) proinflammatory cytokine release, (4) histopathologic lung injury score, and (5) hypoxemia but did not increase bacterial burden. Transcriptomic analyses identified effects of steroid therapy in mice that were also observed in the clinical samples. CONCLUSIONS: In combination with appropriate antibiotic therapy in mice, treatment of pneumococcal pneumonia with steroid therapy reduced hypoxemia, pulmonary edema, lung permeability, and histologic criteria of lung injury, and also altered inflammatory responses at the protein and gene expression level. The transcriptional studies in patients suggest that the mouse model replicates some of the features of pneumonia in patients with Streptococcus pneumoniae and steroid treatment. Overall, these studies provide evidence for the mechanisms that may explain the beneficial effects of glucocorticoid therapy in patients with community acquired pneumonia from Streptococcus Pneumoniae.

Dysregulated neutrophil infiltration and activity in lung tissues are pathogenic features of sepsis-induced acute respiratory distress syndrome (ARDS), an important cause of morbidity and mortality in critically ill patients. Therapeutic reduction of excessive neutrophil transmigration from the vasculature into the distal airspaces to mitigate lung tissue damage and improve survival is an important objective. Human peripheral blood polymorphonuclear neutrophils (PMNs) can be separated into two subsets as recently described: one that readily endocytoses albumin nanoparticles (ANPs) referred to as ANPhigh PMN and another that fails to endocytose ANPs referred to as ANPlow PMN. Here, we tested the hypothesis that targeting ANPhigh human PMNs with ANPs loaded with the drug piceatannol (PANPs), a selective spleen tyrosine kinase (Syk) inhibitor that inhibits β2-integrin signaling, would mitigate lipopolysaccharide (LPS)-induced accumulation of PMNs in human lungs and reduce lung edema. In the present study, human lungs were perfused ex vivo with fresh whole blood containing human PMNs and 6 mg of LPS to induce injury accompanied by PMN infiltration into the lungs. Following the LPS exposure, intravenous injection of PANPs reduced transmigration and accumulation of PMNs in the lungs as determined by bronchoalveolar lavage counts and histologic scoring. A parallel reduction in lung weight gain, a surrogate for pulmonary edema fluid accumulation, suggested protection from edema in this human lung injury model. The results demonstrate the potential of therapeutic drug loading of albumin nanoparticles (PANPs) for targeting an injurious, inflammation-inducing population of PMNs in ARDS patients. [ABSTRACT FROM AUTHOR]

The article reports that prone position reduces mortality in severe acute respiratory distress syndrome (ARDS). Topics include considered that the benefit of prone position is well established during passive mechanical ventilation and the effects of prone position on the determinants of lung injury under spontaneous breathing have not been evaluated yet in ARDS.

Background: Vocal cord paralysis (VCP) is a rare complication of thoracic cardiovascular surgery. In severe cases, life-threatening airway obstruction may occur.Objective: To evaluate the incidence and severity of VCP among patients who underwent thoracic cardiovascular surgery and to identify possible risk factors.Design: Single-centre retrospective review of adult patients.Setting: Osaka University Hospital, Suita, Japan, from January 2013 to August 2015.Patients: We included 688 patients in the final analysis. Preoperative, intraoperative and postoperative data were collected from medical records. Patients with preoperative VCP or tracheostomy prior to extubation were excluded. The VCP severity in relation to functional recovery was graded using the following categories: absent; mild, remission at 6 months; moderate, partial or persistent VCP at 6 months; or severe, airway obstruction after extubation requiring reintubation. An otolaryngologist diagnosed all VCP cases.Main Outcome Measures: The incidence and severity of VCP after extubation.Results: The incidence (number) of VCP was 4.7% (32), with those of mild, moderate and severe VCP being 1.7% (12), 1.5% (10) and 1.5% (10), respectively. The ICU stay was significantly longer in patients with severe VCP than in patients without VCP [12.5 days (interquartile range 5.5 to 25.5) vs. 3 days (interquartile range 2 to 5), P = 0.0002]. In our multivariable analysis, type 2 diabetes mellitus [odds ratio (OR) 1.853, P = 0.009], intubation period (OR per 24 h 1.136, P = 0.014), ascending aortic arch surgery with brachiocephalic artery reconstruction (OR 8.708, P < 0.001) and ventricular assist device implantation (OR 3.460, P = 0.005) were independent predictors for VCP.Conclusion: The identification of these risk factors may facilitate screening for VCP before extubation and possibly help anaesthesia personnel to be prepared to treat VCP-related airway obstruction should it occur. [ABSTRACT FROM AUTHOR]

Due to the coronavirus disease 2019 pandemic, the number of coronavirus disease 2019-associated acute respiratory distress syndrome is rapidly increasing. The heterogeneity of coronavirus disease 2019-associated acute respiratory distress syndrome contributes to the complexity of managing patients. Here we described two patients with coronavirus disease 2019-associated acute respiratory distress syndrome showing that the bedside physiological approach including careful evaluation of respiratory system mechanics and visualization of ventilation with electrical impedance tomography was useful to individualize ventilatory management. [ABSTRACT FROM AUTHOR]

Monocyte-derived macrophages recruited to injured tissues induce a maladaptive fibrotic response characterized by excessive production of collagen by local fibroblasts. Macrophages initiate this programming via paracrine factors, but it is unknown whether reciprocal responses from fibroblasts enhance profibrotic polarization of macrophages. We identify macrophage-fibroblast crosstalk necessary for injury-associated fibrosis, in which macrophages induced interleukin 6 ( IL-6 ) expression in fibroblasts via purinergic receptor P2rx4 signaling, and IL-6, in turn, induced arginase 1 ( Arg1 ) expression in macrophages. Arg1 contributed to fibrotic responses by metabolizing arginine to ornithine, which fibroblasts used as a substrate to synthesize proline, a uniquely abundant constituent of collagen. Imaging of idiopathic pulmonary fibrosis (IPF) lung samples confirmed expression of ARG1 in myeloid cells, and arginase inhibition suppressed collagen expression in cultured precision-cut IPF lung slices. Taken together, we define a circuit between macrophages and fibroblasts that facilitates cross-feeding metabolism necessary for injury-associated fibrosis.

Background: Streptococcus pneumoniae is the most common bacterial cause of community acquired pneumonia and the acute respiratory distress syndrome (ARDS). Some clinical trials have demonstrated a beneficial effect of corticosteroid therapy in community acquired pneumonia, COVID-19, and ARDS, but the mechanisms of this benefit remain unclear. The objective of this study was to investigate the effects of corticosteroids on the pulmonary biology of pneumococcal pneumonia in an observational cohort of mechanically ventilated patients and in a mouse model of bacterial pneumonia with Streptococcus pneumoniae ., Methods: We studied gene expression with lower respiratory tract transcriptomes from a cohort of mechanically ventilated patients and in mice. We also carried out comprehensive physiologic, biochemical, and histological analyses in mice to identify the mechanisms of lung injury in Streptococcus pneumoniae with and without adjunctive steroid therapy., Results: Transcriptomic analysis identified pleiotropic effects of steroid therapy on the lower respiratory tract in critically ill patients with pneumococcal pneumonia, findings that were reproducible in mice. In mice with pneumonia, dexamethasone in combination with ceftriaxone reduced (1) pulmonary edema formation, (2) alveolar protein permeability, (3) proinflammatory cytokine release, (4) histopathologic lung injury score, and (5) hypoxemia but did not increase bacterial burden., Conclusions: The gene expression studies in patients and in the mice support the clinical relevance of the mouse studies, which replicate several features of pneumococcal pneumonia and steroid therapy in humans. In combination with appropriate antibiotic therapy in mice, treatment of pneumococcal pneumonia with steroid therapy reduced hypoxemia, pulmonary edema, lung permeability, and histologic criteria of lung injury, and also altered inflammatory responses at the protein and gene expression level. The results from these studies provide evidence for the mechanisms that may explain the beneficial effects of glucocorticoid therapy in patients with community acquired pneumonia from Streptococcus Pneumoniae ., Competing Interests: -Competing interests The authors declare that they have no competing interests.

A 64-year-old male patient with pheochromocytoma underwent an off-pump coronary artery bypass graft- ing. Determination of order of surgeries, preoperative medical management and intraoperative hemodynamic management are important in these cases. Al- though bolus administration of phenylephrine showed poor response, the surgery was uneventful and the patient remained hemodynamically stable throughout the procedure and perioperative period.

A 53-year-old woman with recurrent abdominal pain was referred to our hospital. Based on the enhanced abdominal computed tomographic (CT) finding, she was diagnosed with intussusception of the sigmoid colon. Colonoscopy was performed to release the intussusception, and a lead point lesion was detected. An advanced cancer was found in the rectum, which could be pushed back into the sigmoid colon easily using pressurized air. A more-advanced colon cancer was also detected on the oral side of the lesion. The patient was diagnosed with double cancer of the sigmoid colon and was treated with laparoscopic sigmoidectomy with lymph node resection (D3). Preliminary reduction by colonoscopy prior to surgery is an effective option in cases of adult intussusception. Colonoscopy can be used to perform definitive and qualitative diagnoses.