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Background and Purpose: Toll‐like receptors 4 (TLR4) and TLR7/TLR8 play an important role in mediating the inflammatory effects of bacterial and viral pathogens. Interleukin‐1 receptor‐associated kinase 4 (IRAK4) is an important regulator of signalling by toll‐like receptor (TLR) and hence is a potential therapeutic target in diseases characterized by increased lung inflammatory signalling. Experimental Approach: We used an established murine model of acute lung inflammation, and studied human lung tissue ex vivo, to investigate the effects of inhibiting IRAK4 on lung inflammatory pathways. Key Results: We show that TLR4 stimulation produces an inflammatory response characterized by neutrophil influx and tumour necrosis factor‐α (TNF‐α) production in murine lungs and that these responses are markedly reduced in IRAK4 kinase‐dead mice. In addition, we characterize a novel selective IRAK4 inhibitor, BI1543673, and show that this compound can reduce lipopolysaccharide (LPS)‐induced airway inflammation in wild‐type mice. Additionally, BI1543673 reduced inflammatory responses to both TLR4 and TLR7/8 stimulation in human lung tissue studied ex vivo. Conclusion and Implications: These data demonstrate a key role for IRAK4 signalling in lung inflammation and suggest that IRAK4 inhibition has potential utility to treat lung diseases characterized by inflammatory responses driven through TLR4 and TLR7/8. [ABSTRACT FROM AUTHOR]

Background Objectives Methods Results Conclusions Respiratory dysfunction is an important contributor to morbidity and mortality in advanced Parkinson's disease (PD), but it is unclear what parameters are sensitive to diagnose and monitor respiratory dysfunction across disease phases.We aimed to characterize respiratory dysfunction in mild to moderate PD.In 20 individuals without cardiopulmonary comorbidity, pulmonary and inspiratory muscle function testing were performed ON‐medication. Subsequently, the acute ventilatory response to hypoxia (HVR) was assessed by gradually decreasing FIO2 from 0.209 (room air) to 0.127, which was compared to eight age‐ and sex‐matched healthy controls under arterial blood gas monitoring. Lastly, on different days, the same 20 individuals with PD underwent six blinded exposures to 45‐min normobaric hypoxia at FiO2 0.163 and 0.127 or placebo OFF‐medication to assess breathing responses.At rest, individuals with greatest PD severity had a lower tidal volume (pairwise comparisons: 0.59 vs. 0.74, P = 0.038–0.050) and tended to have a higher breathing frequency (17.7 vs. 14.4, P = 0.076), despite normal pulmonary function. A 45‐min exposure to hypoxia induced a significantly lower acute HVR in individuals with PD compared to controls (−0.0489 vs. 0.133 L.min/%, P = 0.0038). Acute HVR was reduced regardless of disease severity. Subacute HVR in individuals with milder disease tended to be higher compared to those with more advanced disease (P = 0.079).Respiratory dysfunction is present in individuals with PD, including those with relatively mild disease severity, and is characterized by altered breathing patterns at rest, as well as a lower HVR, despite normal pulmonary and inspiratory muscle function testing. [ABSTRACT FROM AUTHOR]

Diagnosing the cause of death can be challenging, particularly for patients with no prior history of visits to the treating hospital. We encountered a case involving a 76‐year‐old male who was discovered in a state of cardiopulmonary arrest at his home and subsequently declared deceased in our hospital due to severe pneumonia. He had exhibited symptoms of fever over 37°C and severe coughing for several days. Despite consulting a primary care physician one day prior, his symptoms worsened. Autopsy findings revealed an increase in lung weight and diffuse changes in parenchyma. Histological analysis showed numerous inflammatory cells and exudate within the alveoli. Gram and Periodic acid‐Schiff staining were negative, but slight staining was observed in the cytoplasm of macrophages by Warthin‐starry and Gimenez stains. Tests using a pan bacterial/viral detection kit and qualitative polymerase chain reaction (PCR) for Legionella pneumophila were negative. However, using deoxyribonucleic acid extracted from formalin‐fixed paraffin‐embedded lung tissue, PCR amplification of the ssrA gene of congeneric Legionella species yielded positive results. The results suggest that the cause of death was likely due to bacterial pneumonia caused by Legionella species. [ABSTRACT FROM AUTHOR]

Background: Tracheostomy tube changes are a considerable part of the management of patients with tracheostomy and are necessary for preventing aspiration pneumonia, especially in patients with long‐term tracheostomy. The process of tracheostomy tube changes in many patients may not be timely, safe or efficient. Aim: The objectives were to implement a quality improvement intervention that reduces the incidence of aspiration pneumonia in patients with tracheostomy, improve staff knowledge about tracheostomy tube changes and improve staff adherence to documentation. Methods: A pre‐post intervention design was used in this quality improvement project. We created a change strategy bundle that included identification of the need for and observation determination of the timing of tube changes timing, change assessments, identification of the person and location, preparation, co‐operation and maintenance. A tracheostomy tube change workflow was also created. Then, the intervention was implemented in the clinic after staff training. The incidence of aspiration pneumonia, staff knowledge and staff adherence were compared before and after the intervention. Results: Two hundred and 20 patients were enrolled (105 in the preintervention group; 115 in the postintervention group) with 88 tracheostomy tube change episodes (23 in the preintervention group; 65 in the postintervention group). Thirty‐five staff members completed the training and surveys. The incidence of pneumonia decreased from 43.8% to 27.8% after the intervention (p =.013). The knowledge score of staff increased from 46.57 ± 11.10 to 88.14 ± 6.76, and the implementation rate of the audit increased to 67.32%–100%. Conclusions: This quality improvement project regarding tracheostomy changes reduced the incidence of pneumonia, increased staff knowledge about tracheostomy tube changes and improved staff adherence. Relevance to Clinical Practice: A standardized tracheostomy tube change bundle, education, interprofessional collaboration and culture changes were important to ensure the best outcomes in this quality improvement project. These factors improved the timeliness, efficiency and safety of tracheostomy tube changes. [ABSTRACT FROM AUTHOR]

Background: Early initiation of targeted antibiotic therapy is important to achieve the best patient outcomes in intubated patients with pneumonia in the intensive care unit (ICU). This study aimed to investigate the applicability of multiplex polymerase chain reaction (PCR) in an ICU by comparing the test results to the results of conventional microbiological methods to assess the possible impact on antibiotic therapy. Method: This retrospective study investigated adult patients with pneumonia on mechanical ventilation in the ICU. Tracheal aspirates were collected within 24h after intubation and the initiation of mechanical ventilation. Samples were initially tested by conventional microbiological methods and subsequently re‐evaluated with rapid multiplex PCR on stored samples. Concordance between the two methods was assessed. An intensivist and a microbiologist retrospectively reviewed the patients' electronic health records for relevant clinical details to evaluate the potential impact of multiplex PCR results on antibiotic therapy. Results: In this study, 76 patients were enrolled and 55 (72.4%) tested positive for 95 pathogens using multiplex PCR, while conventional microbiological methods identified 40 pathogens in 32 (42.2%) patients. Concordance between the two methods was observed in 42 (55.3%) patients. Multiplex PCR detected 39 additional pathogens in 31 (40.7%) patients. Retrospective analysis indicated potential antibiotic de‐escalation in 35 (46.1%) patients and escalation in 4 (5.3%) patients. Multiplex PCR significantly reduced the turnaround time for test results. Conclusion: In ICU patients with suspected pneumonia, multiplex PCR identified a higher number of pathogens compared to CMM. A retrospective assessment indicates that the use of multiplex PCR could potentially have prompted the de‐escalation of antibiotic therapy in nearly half of the patients. Therefore, multiplex PCR may serve as a supplement to CMM in guiding antibiotic stewardship. [ABSTRACT FROM AUTHOR]

Interleukin (IL)‐33 released from airway epithelial cells plays a vital role in shaping type 2 immune responses by binding to the ST2 receptor present in many immune cells, including mast cells (MCs). Intranasal administration of IL‐33 in mice induces type 2 lung inflammation, an increase in lung MC progenitors, and transepithelial migration of leukocytes to the bronchoalveolar space. The aim of this study was to determine the contribution of MCs in IL‐33‐induced lung pathology. Four daily intranasal administrations of IL‐33 reduced spirometry‐like lung function parameters, induced airway hyperresponsiveness, and increased leukocytes in bronchoalveolar lavage fluid (BAL) in an ST2‐dependent manner. MC‐deficient (Cpa3cre/+) mice, which lack MCs, had intact spirometry‐like lung function but slightly reduced airway hyperresponsiveness, possibly related to reduced IL‐33 or serotonin. Strikingly, Cpa3cre/+ mice exposed to IL‐33 had 50% reduction in BAL T‐cells, and CXCL1 and IL‐33 were reduced in the lung. Intranasal IL‐33 induced CXCR2 expression in T‐cells in a MC‐independent fashion. Furthermore, IL‐33‐induced lung MCs were immunopositive for CXCL1 and localized in the epithelium of wild‐type mice. These results suggest that MCs are required to sustain intact lung IL‐33 and CXCL1 levels in mice with IL‐33‐induced airway inflammation, thereby facilitating T‐cell accumulation in the bronchoalveolar space. [ABSTRACT FROM AUTHOR]

Metal oxide sensor‐based electronic nose (E‐Nose) technology provides an easy to use method for breath analysis by detection of volatile organic compound (VOC)‐induced changes of electrical conductivity. Resulting signal patterns are then analyzed by machine learning (ML) algorithms. This study aimed to establish breath analysis by E‐Nose technology as a diagnostic tool for severe acute respiratory syndrome coronavirus type 2 (SARS‐CoV‐2) pneumonia within a multi‐analyst experiment. Breath samples of 126 subjects with (n = 63) or without SARS‐CoV‐2 pneumonia (n = 63) were collected using the ReCIVA® Breath Sampler, enriched and stored on Tenax sorption tubes, and analyzed using an E‐Nose unit with 10 sensors. ML approaches were applied by three independent data analyst teams and included a wide range of classifiers, hyperparameters, training modes, and subsets of training data. Within the multi‐analyst experiment, all teams successfully classified individuals as infected or uninfected with an averaged area under the curve (AUC) larger than 90% and misclassification error lower than 19%, and identified the same sensor as most relevant to classification success. This new method using VOC enrichment and E‐Nose analysis combined with ML can yield results similar to polymerase chain reaction (PCR) detection and superior to point‐of‐care (POC) antigen testing. Reducing the sensor set to the most relevant sensor may prove interesting for developing targeted POC testing. [ABSTRACT FROM AUTHOR]

Infections are one of the most significant healthcare and economic burdens across the world as underscored by the recent coronavirus pandemic. Moreover, with the increasing incidence of antimicrobial resistance, there is an urgent need to better understand host–pathogen interactions to design effective treatment strategies. The complement system is a key arsenal of the host defense response to pathogens and bridges both innate and adaptive immunity. However, in the contest between pathogens and host defense mechanisms, the host is not always victorious. Pathogens have evolved several approaches, including co‐opting the host complement regulators to evade complement‐mediated killing. Furthermore, deficiencies in the complement proteins, both genetic and therapeutic, can lead to an inefficient complement‐mediated pathogen eradication, rendering the host more susceptible to certain infections. On the other hand, overwhelming infection can provoke fulminant complement activation with uncontrolled inflammation and potentially fatal tissue and organ damage. This review presents an overview of critical aspects of the complement‐pathogen interactions during infection and discusses perspectives on designing therapies to mitigate complement dysfunction and limit tissue injury. [ABSTRACT FROM AUTHOR]

Aim: Methods of predicting severe postoperative complications after anatomical resection for hepatocellular carcinoma are yet to be established. We aimed to clarify the relationship between inflammation‐based prognostic scores and liver fibrosis markers and the incidence of postoperative complications after anatomical resection for hepatocellular carcinoma as well as the usefulness of these markers in surgical procedure selection. Methods: We included 374 patients with hepatocellular carcinoma who had undergone initial hepatectomy between January 2007 and December 2021. The association between inflammation‐based prognostic scores or liver fibrosis markers and postoperative complications was evaluated, and severe postoperative complication rates in the high‐risk group defined by these markers were compared in terms of surgical procedure. Results: The advanced lung cancer inflammation index and nonalcoholic fatty liver disease fibrosis score correlated significantly with severe postoperative complications after anatomical resection, with areas under the curve of 0.67 and 0.61, respectively. The combined advanced lung cancer inflammation index and nonalcoholic fatty liver disease fibrosis score resulted in a larger area under the curve (0.69). Furthermore, in the high‐risk group determined by the combined score, the anatomical resection group had a significantly higher incidence of severe complications than the partial resection group (P < 0.01). There were no significant differences in prognosis among the surgical procedures in the high‐risk group. Conclusion: The combined advanced lung cancer inflammation index and nonalcoholic fatty liver disease fibrosis score serves as a predictive marker for severe postoperative complications after anatomical resection. This combined marker may contribute to appropriate surgical procedure selection. [ABSTRACT FROM AUTHOR]

Background Methods Results Conclusions Severe refractory, neutrophilic asthma remains an unsolved clinical problem. STING agonists induce a neutrophilic response in the airways, suggesting that STING activation may contribute to the triggering of neutrophilic exacerbations. We aim to determine whether STING‐induced neutrophilic lung inflammation mimics severe asthma.We developed new models of neutrophilic lung inflammation induced by house dust mite (HDM) plus STING agonists diamidobenzimidazole (diABZI) or cGAMP in wild‐type, and conditional‐STING‐deficient mice. We measured DNA damage, cell death, NETs, cGAS/STING pathway activation by immunoblots, N1/N2 balance by flow cytometry, lung function by plethysmography, and Th1/Th2 cytokines by multiplex. We evaluated diABZI effects on human airway epithelial cells from healthy or patients with asthma, and validated the results by transcriptomic analyses of rhinovirus infected healthy controls vs patients with asthma.DiABZI administration during HDM challenge increased airway hyperresponsiveness, neutrophil recruitment with prominent NOS2+ARG1− type 1 neutrophils, protein extravasation, cell death by PANoptosis, NETs formation, extracellular dsDNA release, DNA sensors activation, IFNγ, IL‐6 and CXCL10 release. Functionally, STING agonists exacerbated airway hyperresponsiveness. DiABZI caused DNA and epithelial barrier damage, STING pathway activation in human airway epithelial cells exposed to HDM, in line with DNA‐sensing and PANoptosis pathways upregulation and tight‐junction downregulation induced by rhinovirus challenge in patients with asthma.Our study identifies that triggering STING in the context of asthma induces cell death by PANoptosis, fueling the flame of inflammation through a mixed Th1/Th2 immune response recapitulating the features of severe asthma with a prognostic signature of type 1 neutrophils. [ABSTRACT FROM AUTHOR]

Background Objective Methods Results Conclusion The role of lung group 2 innate lymphoid cell (ILC2) activation in allergic asthma is increasingly established. However, the regulatory mechanisms underlying hypoxia‐inducible factor‐1α (HIF‐1α)‐mediated glycolysis in ILC2‐mediated allergic airway inflammation remain unclear.To investigate the role of the HIF‐1α/glycolysis axis in ILC2‐mediated allergic airway inflammation.Glycolysis and HIF‐1α inhibitors were used to identify their effect on the function and glucose metabolism of mouse and human ILC2s in vivo and vitro. Blocking glycolysis and HIF‐1α in mice under interleukin‐33 (IL‐33) stimulation were performed to test ILC2 responses. Conditional HIF‐1α‐deficient mice were used to confirm the specific role of HIF‐1α in ILC2‐driven airway inflammation models. Transcriptomic, metabolic, and chromatin immunoprecipitation analyses were performed to elucidate the underlying mechanism.HIF‐1α is involved in ILC2 metabolism and is crucial in allergic airway inflammation. Single‐cell sequencing data analysis and qPCR confirmation revealed a significant upregulation of glycolysis‐related genes, particularly HIF‐1α, in murine lung ILC2s after IL‐33 intranasal administration or injection. Treatment with the glycolysis inhibitor 2‐deoxy‐D‐glucose (2‐DG) and the HIF‐1α inhibitor 2‐methoxyestradiol (2‐ME) abrogated inflammation by suppressing ILC2s function. Conditional HIF‐1α‐deficient mice showed reduced ILC2 response and airway inflammation induced upon IL‐33 or house dust mite (HDM) stimulation. Transcriptome and metabolic analyses revealed significantly impaired glycolysis in lung ILC2s in conditional HIF‐1α knockout mice compared to that in their littermate controls. Chromatin immunoprecipitation results confirmed the transcriptional downregulation of glycolysis‐related genes in HIF‐1α‐knockout and 2‐DG‐treated mice. Furthermore, impaired HIF‐1α/glycolysis axis activation is correlated with downregulated ILC2 in patients with asthma.The HIF‐1α/glycolysis axis is critical for controlling ILC2 responses in allergic airway inflammation and has potential immunotherapeutic value in asthma. [ABSTRACT FROM AUTHOR]

Background Objectives Animals Methods Results Conclusions and Clinical Importance Respirable mineral particles can induce lower airway inflammation, but the role they play in asthma of horses is unknown.Respirable mineral particles, particularly respirable silica, are an overlooked determinant of chronic lung inflammation (asthma) in horses.Twenty‐three horses from an equine hospital population: 11 moderately affected (MEA), 7 severely asthmatic (SEA), and 5 control horses free from respiratory clinical signs.Prospective observational study. The quantity and quality of mineral particles found in bronchoalveolar lavage fluid (BALF) were characterized, with particular attention to silica content. Polarized light microscopy performed on cytospin slides identified intracellular birefringent particles as silica. Spectrometry‐based analysis performed on whole BALF determined total mineral and silica percentage and concentration. Group‐related differences in BALF mineral and silica load were investigated as well as associations with BALF cytology.Intracellular birefringent particles were increased in SEA vs MEA (median [interquartile range, IQR]), 12 [7] vs 4 [5] particles/30 high power fields [hpf], respectively; P = .01) and vs controls (4 [2] particles/30 hpf; P = .02). Total mineral concentration in BALF was similar between the groups studied, whereas silica concentration and percentage were increased in SEA vs MEA (1758 [887] particles/mL and 20 [10]% vs 867 [662] particles/mL and 8 [6]%; P = .009 and P = .001) and control group (355 [330] particles/mL and 6 [3]%; P = .0003 and P = .002). Silica load in BALF was associated with BALF neutrophilia in MEA and SEA.Respirable silica is associated with neutrophilic lower airway inflammation in horses and might contribute to asthma development. [ABSTRACT FROM AUTHOR]

Summary This case report describes the clinical presentation, surgical treatment, post‐operative management and outcome of a bronchocutaneous fistula with intrathoracic abscessation in a yearling horse. The animal was presented with a history of several months of persistent coughing and a cutaneous fistula located over the right ventral hemithorax. The yearling had purulent discharge similar in character from both nares and draining out of the fistula. A bronchocutaneous fistula with intrathoracic abscessation was diagnosed by endoscopic examination of the cutaneous fistula. The treatment initially consisted of cyanoacrylate applied topically to the affected bronchi under endoscopic guidance, which was not successful. The fistula was successfully sealed with a diode laser used to create local inflammation at the site. One week after the second intervention, the patient's clinical signs resolved and the fistula was completely sealed 10 weeks following intervention. Follow‐up at 16 months revealed that the patient was doing well and clinically normal. [ABSTRACT FROM AUTHOR]

Background and Aim Methods Results Conclusion This study aimed to investigate the relationship between advanced lung cancer inflammation index (ALI) and non‐alcoholic fatty liver disease (NAFLD) and advanced liver fibrosis (AF).A total of 5642 individuals from the National Health and Nutrition Examination Survey (NHANES) between 2017 and 2020 were examined. Limited cubic spline regression model, and weighted logistic regression were employed to determine if ALI levels were related to the prevalence of NAFLD and AF. Additionally, a mediating analysis was conducted to investigate the role of lipid biomarkers, such as total cholesterol (TC) and high‐density lipoprotein cholesterol (HDL‐C), in the effects of ALI on the prevalence of NAFLD and AF.After adjusting for potential confounders, a significant positive association was found between ALI with NAFLD and AF prevalence. Compared with those in ALI Tertile 1, participants in Tertile 3 had higher odds of NAFLD prevalence (odds ratio [OR]: 3.16; 95% confidence interval [CI]: 2.52–3.97) and AF (OR: 3.17; 95% CI: 2.30–4.36). Participants in both Tertile 2 and Tertile 3 had lower odds of developing AF (P for trend = 0.005). Moreover, we discovered a nonlinear association between ALI and NAFLD. An inflection point of 74.25 for NAFLD was identified through a two‐segment linear regression model. Moreover, TC and HDL‐C levels mediated the association between ALI and NAFLD by 10.2% and 4.2%, respectively (both P < 0.001).Our findings suggest that higher ALI levels are positively associated with an increased prevalence of NAFLD and AF, partly mediated by lipid biomarkers. [ABSTRACT FROM AUTHOR]

Background: Enteral nutrition may affect risks of gastrointestinal bleeding, pneumonia and mortality in critically ill patients and may also modify the effects of pharmacological stress ulcer prophylaxis. We undertook post hoc analyses of the stress ulcer prophylaxis in the intensive care unit trial to assess for any associations and interactions between enteral nutrition and pantoprazole. Methods: Extended Cox models with time‐varying co‐variates and competing events were used to assess potential associations, adjusted for baseline severity of illness. Potential interactions between daily enteral nutrition and allocation to pantoprazole on outcomes were similarly assessed. Results: Enteral nutrition was associated with lower risk of clinically important gastrointestinal bleeding (cause‐specific hazard ratio [HR]: 0.29, 95% confidence interval: [CI] 0.19–0.44, p <.001), higher risk of pneumonia (HR: 1.44, 95% CI: 1.14–1.82, p =.003), and lower risk of all‐cause mortality (HR: 0.22, 95% CI: 0.18–0.27, p <.001). Enteral nutrition with allocation to pantoprazole was associated with a lower risk of mortality (HR: 0.27, 95% CI: 0.21–0.35, p <.001), similar to enteral nutrition with allocation to placebo (HR: 0.17, 95% CI: 0.13–0.23, p <.001). Allocation to pantoprazole with no enteral nutrition had little effect on mortality (HR: 0.83, 95% CI: 0.63–1.09, p =.179), whilst allocation to pantoprazole and receipt of enteral nutrition was mostly compatible with increased all‐cause mortality (HR: 1.27, 95% CI: 0.99–1.64, p =.061). The test of interaction between enteral nutrition and pantoprazole treatment allocation for all‐cause mortality was statistically significant (p =.024). Conclusions: Enteral nutrition was associated with an increased risk of pneumonia and a reduced risk of gastrointestinal bleeding. The interaction between pantoprazole and enteral nutrition suggesting an increased risk of mortality requires further study. [ABSTRACT FROM AUTHOR]

Background: We aimed to investigate the relationship between systemic immune‐inflammation index (SII) and short‐term mortality in acute ischemic stroke (AIS) with internal carotid artery (ICA) severe stenosis and stroke associated pneumonia (SAP) patients. Methods: Information on general demographic, laboratory data, CT angiography, magnetic resonance angiography, or digital subtraction angiography were obtained. The predictive power was evaluated by assessing the area under the receiver operating characteristic (ROC) curve. The logistic regression was performed to assess the association of SII and short‐term mortality in severe stenosis ICA‐AIS and SAP patients. Result: Among 342 patients with severe stenosis ICA‐AIS and SAP, death occurred in 66 patients during 120 days follow‐up. Multivariate regression analyses indicated that increased SII predicts higher mortality in 120 days follow‐up, and the risk of short‐term mortality in SII > 666.31 × 109/L group is increased 4.671‐fold. Patients with SII > 666.31 × 109/L had higher proportion of male, hypertension, smoking, higher admission NIHSS score, higher systolic blood pressure, and higher proportion of 120 days mortality. Higher SII predicted a worse 120 days mortality was worked out by Kaplan–Meier methods. Conclusion: An elevated SII was remarkably associated with 120 days mortality in severe stenosis ICA‐AIS and SAP patients. [ABSTRACT FROM AUTHOR]

Introduction: Various bronchoscopic guidance techniques have emerged to improve the diagnostic yield of peripheral pulmonary lesions (PPLs), especially when combined with ultra‐thin bronchoscopy. However, uncertainties exists in the convenience, accuracy rate, and complications of these techniques. We compared the feasibility, accuracy rate, and complication rates of transbronchial biopsy of PPLs sampled by the standard thin‐layer CT navigation combined with ultrathin bronchoscopy (CTNUTB), the Lungpro virtual navigation combined with ultrathin bronchoscopy (VNUTB), and electromagnetic navigation combined with ultrathin bronchoscopy (ENUTB). Methods: Retrospectively identified were 256 patients sampled with transbronchial biopsy of PPLs. Eligible patients referred for CTNUTB, VNUTB, and ENUTB from January 2017 to December 2021 were included. We comprehensively compared the accuracy rate, feasibility, and complication rates for each method. Results: There was no significant difference in the accuracy rate of CTNUTB, VNUTB, and ENUTB (p = 0.293). The operation time via Lungpro navigation was the shortest (14.4 min, p < 0.001). The planning time via CT planning was the shortest (7.36 min, p < 0.001). There was no difference in the incidence of complications such as hemorrhage, pneumonia, and pneumothorax (p = 0.123). Besides, ENUTB costs more than $2000, while CTNUTB and VNUTB cost only about $130–230. Conclusion: CTNUTB is still the main bronchoscopy method we recommended, which has low cost, simple operation, and safety no less than the others. In contrast, ENUTB provides a higher accuracy rate for small diameter nodules (less than 2 cm), which has a high use value and is worth promoting in the future. [ABSTRACT FROM AUTHOR]

Gut microbiota is an intricate microbial community containing bacteria, fungi, viruses, archaea, and protozoa, and each of them contributes to diverse aspects of host health. Nevertheless, the influence of interaction among gut microbiota on host health remains uncovered. Here, we showed that the interaction between intestinal fungi and bacteria shaped lung inflammation during infection. Specifically, antifungal drug‐induced dysbiosis of gut mycobiota enhanced lung inflammation during infection. Dysbiosis of gut mycobiota led to gut Escherichia coli (E. coli) overgrowth and translocation to the lung during infection, which induced lung accumulation of the CD45+F4/80+Ly6G−Ly6C−CD11b+CD11c+ macrophages. Clearance of macrophages or deletion of TLR4 (Toll‐like receptor 4, recognition of LPS) rather than Dectin‐1 (recognition of beta‐1,3/1,6 glucans on fungi) blocked the antifungal drug‐induced aggravation of lung inflammation during infection. These findings suggest that the interaction between intestinal mycobiota and commensal bacteria affects host health through the gut–lung axis, offering a potential therapeutic target for ameliorating lung inflammation during infection. Highlights: Antifungal drug‐induced dysbiosis of gut mycobiota aggravates lung inflammation during infection.Dysbiosis of intestinal mycobiota results in gut Escherichia coli overgrowth and translocation to the lung during infection.E. coli induces lung accumulation of the CD45+F4/80+Ly6G−Ly6C−CD11b+CD11c+ macrophages.Clearance of macrophages or deletion of TLR4 blocks the antifungal drug‐induced aggravation of lung inflammation during infection. [ABSTRACT FROM AUTHOR]

Background: Pneumonia accounts for over half a million older adult emergency department (ED) visits annually, but ED pneumonia diagnosis is inaccurate. Geriatric‐specific pneumonia diagnostic criteria exist for other settings; no prospective data exist to determine if application in the older adult ED population is feasible. The objective was to prospectively evaluate the utility of four current diagnostic criteria (Loeb; Modified McGeer; Infectious Disease Society of America/American Thoracic Society; American College of Emergency Physicians) in older adult ED patients. Methods: This was a prospective, observational cohort study of older adult ED patients ≥65 years of age in two U.S. EDs with suspected pneumonia defined as having chest radiography ordered and treating physician suspicion. The standard we used for defining the presence, absence, or inability to determine a diagnosis of pneumonia diagnosis was expert physician chart adjudication. We report the summary statistics for demographic characteristics and symptoms/exam findings and sensitivity, specificity, and likelihood ratios with 95% confidence intervals of the existing diagnostic criteria. Pre‐specified cutoff values of a positive LR >10 and a negative LR <0.3 were considered clinically significant. Results: Of 135 patients enrolled, 27 had pneumonia by adjudicator review. Typical patient‐reported pneumonia symptoms, such as fever (18.5%) and new/worse cough (51.9%), were not consistently present in pneumonia. The IDSA/ATS and ACEP criteria had positive LR >10 and negative LR <0.3; however, all confidence intervals included pre‐specified cutoffs. Conclusions: Older adults presented to the ED with low frequency of typical pneumonia symptoms. Although existing diagnostic definitions had promising test characteristics, they may not perform well enough for clinical application without refinement. [ABSTRACT FROM AUTHOR]

Key points: Complications in combined surgery are equivalent to ESS but are higher than rhinoplasty alone.The most common complications are pneumonia, stroke, and epistaxis.Rhinoplasty surgeries with graft use have a higher risk of complications. [ABSTRACT FROM AUTHOR]

We present a unique case of metastatic metaplastic breast carcinoma responding dramatically to immunochemotherapy. A 46‐year‐old Japanese woman with primary metaplastic carcinoma of the breast, which was immunohistochemically confirmed to be triple‐negative breast cancer, underwent radical surgery, followed by adjuvant chemotherapy with an anthracycline and a taxane. Since multiple lung metastases were detected two months post‐chemotherapy and the primary site was shown to be PD‐L1‐positive, the immune checkpoint inhibitor (ICI) pembrolizumab plus gemcitabine/carboplatin was initiated. While the treatment was discontinued after 15 days due to suspected drug‐induced pneumonitis, the lung metastases significantly shrank with no development of new lesions for three months. The patient remained alive as of approximately 15 months after the recurrence date. This case highlights the potential of immunochemotherapy in treating metaplastic breast carcinomas. [ABSTRACT FROM AUTHOR]

Objectives: This comprehensive bibliometric analysis explores the evolving trends in antimicrobial stewardship programs for enhancing treatment and diagnostics of pneumonia from 2006 to 2023. Materials and methods: This research included a performance analysis and science mapping using RStudio v.4.3.1 and the bibliometric R‐package, with a data analysis conducted using Biblioshiny and Scopus. The study identified publication trends, prolific journals, leading institutions and authors, collaboration patterns, and keyword frequencies. Results: The study, based on 789 relevant studies from 287 sources, reveals a substantial increase in publications, collaborative authorship, and citations, with an average of 14.37 citations per document. The Annual Growth Rate for this research domain exhibits a steady increase of 30.13%, emphasizing the expanding scope of research output. Twelve key journals are identified using Bradford's Law with "Antibiotics" being the most prolific, contributing 6.5% of the total articles during the study period. Leading institutions in this research domain include the All‐India Institute of Medical Sciences and the University of Cape Town, each with 21 articles, reflecting their commitment. Dr. S.E. Cosgrove emerges as a key author with eight contributions, followed by other influential contributors. The United States leads in the number of publications, with Italy and Spain following closely. The analysis reveals a concentration of research output in high‐income countries, raising questions about accessibility and research capabilities in lower‐income nations. Addressing these disparities is crucial for comprehensive global strategies in pneumonia management. The study acknowledges limitations, such as database selection and language bias. Conclusion: The research trends in antimicrobial stewardship for pneumonia treatment and diagnostics demonstrate a global increase in scholarly output. These findings provide valuable insights into collaborative networks, influential authors, leading institutions, and emerging topics. [ABSTRACT FROM AUTHOR]

Background: Previous research highlighted variability in electrocardiogram (ECG) readings across patient positions, particularly in the context of COVID‐19 patients with pulmonary complications requiring prone positioning as part of the treatment. Objective: This study aimed to elucidate the effects of prone positioning on ECG parameters and explore its association with the severity of COVID‐19. Methods: A prospective cohort study involved 60 patients diagnosed with COVID‐19 and presenting pulmonary complications. ECGs were recorded in both supine and prone positions, and analyzed for various parameters including heart rate, QRS axis, and QTc interval. Clinical severity was assessed using APACHE II scores and SpO2/FiO2 ratios. Results: Prone positioning led to an increase in heart rate (mean difference: 2.100, 95% CI: 0.471–3.729, p = 0.012), with minor shifts in the QRS axis. Heart rate and QRS axis demonstrated strong positive correlations between positions, with Pearson's correlation coefficients of 0.927 and 0.894, respectively. The study also found a significant association between prolonged QTc intervals in the prone position and elevated APACHE II scores, with a relative risk of 10.75 (95% CI: 1.82–63.64, p = 0.008). Conclusions: The prone positioning caused minor yet significant changes in heart rate and QRS axis. The correlation of prolonged QTc intervals in the prone position with higher APACHE II scores suggests the prognostic relevance of prone ECG in COVID‐19 patients. However, further research is needed to fully understand the clinical implications and mechanisms of these findings. [ABSTRACT FROM AUTHOR]

An association among the use of angiotensin converting enzyme (ACE) inhibitors and angiotensin‐receptor blockers (ARBs) with the clinical outcomes of coronavirus disease 2019 (COVID‐19) is unclear. PubMed, EMBASE, MedRxiv, and BioRxiv were searched for relevant studies that assessed the association between application of ACEI/ARB and risk of COVID‐19, inflammation level, severity COVID‐19 infection, and death in patients with COVID‐19. Ten studies were included with 13,944 patients. ACEI/ARB therapy might be associated with the reduced inflammatory factor (interleukin‐6) and elevated immune cells counts (CD3, CD8). Meta‐analysis showed no significant increase in the risk of COVID‐19 infection (odds ratio [OR]: 0.95, 95% CI: 0.89‐1.05) in patients receiving ACEI/ARB therapy, and ACEI/ARB therapy was associated with a decreased risk of severe COVID‐19 (OR: 0.75, 95% CI: 0.59‐0.96, p = 0.02) and mortality (OR: 0.57, 95% CI: 0.37‐0.87, p = 0.009). Subgroup analyses showed among the general population, ACEI/ARB therapy was not associated with reduced risks of severe COVID‐19 infection (OR: 0.85, 95% CI: 0.66‐1.08, p = 0.19) and all‐cause mortality (OR: 0.31, 95% CI: 0.13‐0.75), and COVID‐19 infection (OR: 0.97, 95% CI: 0.89‐1.05, p = 0.45) were not increased. Among patients with hypertension, the use of an ACEI/ARB was associated with a non‐significant lower severity of COVID‐19 (OR: 0.73, 95% CI: 0.51‐1.03, p = 0.07) and significant lower mortality (OR: 0.57, 95% CI: 0.37‐0.87, p = 0.009), without evidence of an increased risk of COVID‐19 infection (OR: 1.00, 95% CI: 0.90‐1.12, p = 1.00). On the basis of the available evidence, ACEI/ARB therapy should be continued in patients who are at risk for, or have COVID‐19, either in general population or hypertension patients. Our results need to be interpreted with caution considering the potential for residual confounders, and more well‐designed studies that control the clinical confounders are necessary to confirm our findings. [ABSTRACT FROM AUTHOR]

Exploring effective antibacterial approaches for targeted treatment of pathogenic bacterial infections with reduced drug resistance is of great significance. Combinational treatment modality that leverages different therapeutic components can improve the overall effectiveness and minimize adverse effects, thus displaying considerable potential against bacterial infections. Herein, red blood cell membrane fuses with macrophage membrane to develop hybrid cell membrane shell, which further camouflages around drug‐loaded liposome to fabricate biomimetic liposome (AB@LRM) for precise antibacterial therapy. Specifically, photoactive agent black phosphorus quantum dots (BPQDs) and classical antibiotics amikacin (AM) are loaded in AB@LRM to accurately target the inflammatory sites through the guidance of macrophage membrane and long residence capability of red blood cell membrane, eventually exerting efficacious antibacterial activities. Besides, due to the excellent photothermal and photodynamic properties, BPQDs act as an efficient antibacterial agent when exposed to near‐infrared laser irradiation, dramatically increasing the sensitivity of bacteria to antibiotics. Consequently, the synergistic sterilizing effect produced by AB@LRM further restricts bacterial resistance. Upon laser irradiation, AB@LRM shows superior anti‐inflammatory and antibacterial properties in models of P. aeruginosa‐infected pneumonia and wounds. Hence, this light‐activatable antibacterial nanoplatform with good biocompatibility presents great potential to advance the clinical development in the treatment of bacterial infections. [ABSTRACT FROM AUTHOR]

Aim: Chest computed tomography (CT) scan is useful to evaluate the type and extent of lung lesions in coronavirus disease 2019 (COVID‐19) pneumonia. This study explored the association between radiological parameters and various circulating serum‐derived markers, including microRNAs, in older patients with COVID‐19 pneumonia. Methods: A retrospective analysis was designed to study geriatric patients (≥75 years) with COVID‐19 pneumonia, who underwent chest CT scan on admission, and for whom clinical data and serum samples were obtained. To quantify the extent of lung involvement, CT‐score, the percentage of healthy lung (HL%), the percentage of ground glass opacity (GGO%), and the percentage of lung consolidation were assessed using computer‐aided tools. The association of these parameters with two circulating microRNAs, miR‐483‐5p and miR‐320b, previously identified as biomarkers of mortality risk in COVID‐19 geriatric patients, was tested. Results: A total of 73 patients with COVID‐19 pneumonia were evaluable (median age 85 years; interquartile range 82–90 years). Among chest CT‐derived parameters, the percentage of lung consolidation (HR 1.08, 95% CI 1.02–1.14), CT‐score (HR 1.14, 95% CI 1.03–1.25), and HL% (HR 0.97, 95% CI 0.95–0.99) emerged as significant predictors of mortality, whereas non‐significant trends toward increased mortality were observed in patients with higher GGO%. We also found a significant positive association between serum miR‐483‐5p and GGO% (correlation coefficient 0.28; P = 0.018) and a negative association with HL% (correlation coefficient −0.27; P = 0.023). Conclusions: Overall, the extent of lung consolidation can be confirmed as a prognostic parameter of COVID‐19 pneumonia in older patients. Among various serum‐derived markers, miR‐483‐5p can help in exploring the degree of lung involvement, due to its association with higher GGO% and lower HL%. Geriatr Gerontol Int 2024; 24: 962–972. [ABSTRACT FROM AUTHOR]

Introduction: Melioidosis may occasionally be encountered in non‐endemic areas and medical imaging is frequently used to identify and characterise sites of disease. The purpose of this study is to describe the spectrum of imaging findings encountered in melioidosis patients treated in the tertiary public hospitals of Perth, Western Australia, between 2002 and 2022. Methods: A database search and electronic medical record review was used to identify cases. Cases were included if they had Burkholderia pseudomallei isolated on culture and if they had at least one diagnostic imaging study performed at a Perth public tertiary hospital. The relevant imaging studies were reviewed, and imaging findings were recorded. Results: Thirty‐six cases were identified. The most common disease manifestation was bacteraemia (72%, 26 cases), followed by pulmonary infection (58%, 21 cases), skin and soft tissue infection (22%, eight cases), prostate abscess (14%, five cases) and septic arthritis (6%, two cases). A previously unreported case of isolated melioid pleural effusion was identified, as was a case of reactivated chronic latent pulmonary melioidosis with an apparent delay of over 20 years between the onset of symptoms and the time of infection. In cases with pulmonary melioidosis, the major lung abnormalities on CT chest could be categorised into one of two distinct patterns: nodular‐predominant (78%) or consolidation‐predominant (22%). Conclusion: Further research is required to assess the utility of the pattern‐based categorisation of lung abnormalities on CT chest seen in the pulmonary melioidosis cases of this series. [ABSTRACT FROM AUTHOR]

Objectives: In cystic fibrosis (CF), an imbalanced lipid metabolism is associated with lung inflammation. Little is known about the role that specific lipid mediators (LMs) exert in CF lung inflammation, and whether their levels change during early disease progression. Therefore, we measured airway LM profiles of young CF patients, correlating these with disease‐associated parameters. Methods: Levels of omega (ω)‐3/6 PUFAs and their LM derivatives were determined in bronchoalveolar lavage fluid (BALF) of children with CF ages 1–5 using a targeted high‐performance liquid chromatography–tandem mass spectrometry approach. Hierarchical clustering analysis was performed on relative LM levels. Individual relative LM levels were correlated with neutrophilic inflammation (BALF %Neu) and structural lung damage (PRAGMA‐CF %Disease). Significant correlations were included in a backward multivariate linear regression model to identify the LMs that are best related to disease progression. Results: A total of 65 BALF samples were analysed for ω‐3/6 lipid content. LM profiles clustered into an arachidonic acid (AA)‐enriched and a linoleic acid (LA)‐enriched sample cluster. AA derivatives like 17‐OH‐DH‐HETE, 5‐HETE, 5,15‐diHETE, 15‐HETE, 15‐KETE, LTB4 and 6‐trans‐LTB4 positively correlated with BALF %Neu and/or PRAGMA %Dis. Contrastingly, 9‐HoTrE and the LA derivatives 9‐HoDE, 9(10)‐EpOME, 9(10)‐DiHOME, 13‐HoDE, 13‐oxoODE and 12(13)‐EpOME negatively correlated with BALF %Neu and/or PRAGMA %Dis. 6‐trans‐LTB4 was the strongest predictor for BALF %Neu. 5‐HETE and 15‐KETE contributed most to PRAGMA %Dis prediction. Conclusions: Our data provide more insight into the lung lipidome of infants with CF, and show that a shift from LA derivatives to AA derivatives in BALF associates with early CF lung disease progression. [ABSTRACT FROM AUTHOR]

An 18‐year‐old healthy male complained of a 7‐day history of fever, cough, and sore throat, along with a three‐day history of left facial swelling. The x‐rays revealed subcutaneous emphysema in the chest, neck, face, and mediastinum region (Pneumomediastinum). Furthermore, an area of infiltration was visible, indicating pneumonia. Therefore, we immediately started him on intravenous antibiotics. We then moved the patient to an isolation room, considering pulmonary tuberculosis as one of the differential diagnoses. However, the Acid Fast Bacilli (AFB), Mycobacterium Tuberculosis Bacteria‐Polymerase Chain Reaction (MTB PCR), and sputum for gram stain and culture were all negative. On the other hand, the test for parainfluenza virus 3 was positive. The patient was observed with a daily chest x‐ray to monitor the progress of pneumonia and subcutaneous emphysema. Fortunately, the subcutaneous emphysema was significantly reduced on a daily basis until it was completely resolved before discharge home. [ABSTRACT FROM AUTHOR]

Immune checkpoint inhibitors (ICI) are increasingly utilized as first‐line treatment for many solid tumour malignancies. One downside of ICI therapy is autoimmune‐mediated organ inflammation, or immune‐related adverse events (irAE). ICI‐related pneumonitis, or non‐infectious inflammation of the lung, is a well‐described irAE. While guidelines surrounding ICI‐related pneumonitis are well established, other ICI‐related pulmonary toxicities, including reactive airways disease, are rarely described in the literature. Here, we present a series of patients without pre‐existing COPD or asthma who developed reactive airways disease with peripheral eosinophilia after ICI therapy and without radiographic evidence of pneumonitis. The patients were treated with typical therapies for reactive airways disease, including– inhaled steroids, bronchodilators, systemic steroids, and in one instance, dupilumab. All experienced symptomatic improvement with these therapies, enabling some of the patients to continue receiving ICI therapy. [ABSTRACT FROM AUTHOR]

Background: Bronchoalveolar lavage (BAL) is a common procedure for evaluation of the equine lower airways. Time to resolution of post‐BAL inflammation has not been clearly defined. Hypothesis: Residual inflammation, evident by changes in immune cell populations and inflammatory cytokines, will resolve by 72 hours after BAL. Animals: Six adult, healthy, institution‐owned horses. Methods: Randomized, complete cross‐over design. Each horse underwent 3 paired BALs, including a baseline and then 48, 72, and 96 hours later, with a 7‐day washout between paired BALs. Each sample underwent cytological evaluation and cytokine concentrations were determined by a commercially available multiplex bead immunoassay. Statistical analysis was performed by multilevel mixed‐effects Poisson regression analysis. Data are reported as marginal means and 95% confidence interval (CI). Results: Neutrophil, eosinophil and mast cell percentages were not significantly different at any time points. Macrophage percentages were higher at 72 hours (45.0 [95% CI, 41.6‐48.4]%) and 96 hours (45.3 [95% CI, 42.9‐47.7]%) vs baseline (37.4 [95% CI, 33.5‐41.4]%; P <.001 and P =.01, respectively), and at 72 hours and 96 hours vs 48 hours (31.9 [95% CI, 28.1‐35.6]%; P <.001). Neutrophil percentage was not significantly increased at 48 hours (P =.11). Interleukin (IL)‐6 concentration was increased at 72 hours (5.22 [95% CI, 3.44‐6.99] pg/mL) vs 48 hours (4.38 [95% CI, 2.99‐5.78] pg/mL; P <.001). Conclusions and Clinical Importance: Significant lung inflammation was not detected at 72 and 96 hours, suggesting that repeating BAL at 72 hours or more can be done without concern of residual inflammation. [ABSTRACT FROM AUTHOR]

Key Clinical Message: Pulmonary sequestration is uncommon congenital malformation. It is important to consider pulmonary sequestration even in young adults presenting with recurrent pneumonic symptoms because prompt surgical intervention is both feasible and curative. Moreover, in health settings lacking CT/MRI angiography service, pulmonary sequestration can be easily misdiagnosed as smear negative pulmonary tuberculosis. Therefore, strong clinical suspicion is required to prevent patient mismanagement. [ABSTRACT FROM AUTHOR]

Pseudomonas aeruginosa infection causes pneumonia and sepsis. Previous research found that X‐ray radiation can induce P. aeruginosa to release outer membrane vesicles (OMVs) of relatively consistent sizes. This study found that OMVs derived from X‐ray‐irradiated P. aeruginosa can significantly inhibit lung leakage, inflammatory cell infiltrating into lung, and the production of pro‐inflammatory cytokines, IL‐1β and TNFα caused by P. aeruginosa infection under preventive and therapeutic administration conditions. Under the same conditions, OMVs also significantly alleviated pathological characteristics of lung injury, including pulmonary edema, pulmonary hemorrhage, and alveolar wall thickening. OMVs also significantly reduced bacterial burdens in peritoneal cavity, accompanied by a reduction in the number of viable bacteria capable of forming bacterial colonies. Pretreating macrophages and neutrophils with OMVs enhances their bactericidal ability. When bacteria were cocultured with treated cells, the number of viable bacteria capable of forming bacterial colonies was significantly reduced. OMVs themselves have not been shown to cause any lung injury or affect bacterial viability. Therefore, OMVs derived from X‐ray‐irradiated P. aeruginosa may not only be applied in prevention and treatment of diseases associated with P. aeruginosa infection, but also served as an excellent vaccine development platform. [ABSTRACT FROM AUTHOR]

Background: Previous studies involving risk–benefit analysis of trastuzumab deruxtecan (DS‐8201) have indicated the benefit of this treatment, although it may increase the risk of interstitial lung disease (ILD) and/or pneumonitis in certain patients. This study aimed to assess the safety of DS‐8201. Methods: A search was done for relevant articles in four electronic databases: PubMed, Embase, the Cochrane Library, and ClinicalTrials.gov. All reports published up until November 2, 2022, were included, and study types were restricted to clinical trials; the last search was then updated to January 10, 2023. We also assessed the quality of the literature with the Cochrane Handbook for Systematic Reviews of Interventions and the Methodological Index for Non‐Randomized Studies tool, and then performed a meta‐analysis with R version 4.2.1. Results: A total of 1428 patients reported in 13 articles were included in this study. The analysis revealed that the most common all‐grade treatment‐emergent adverse events (TEAEs) were nausea and fatigue. The most common TEAE of grade 3 or above (grade ≥3) was neutropenia. The incidences of ILD and/or pneumonitis for all‐grade and grade ≥3 TEAEs were 12.5% and 2.2%, respectively. Conclusions: This comprehensive summary of the incidence of TEAEs associated with DS‐8201 in clinical trials provides an important guide for clinicians. The most common TEAEs were gastrointestinal reactions and fatigue; meanwhile, the most common grade ≥3 TEAE was hematological toxicity. ILD and/or pneumonitis were specific adverse drug reactions associated with DS‐8201, of which physicians should be particularly aware for their higher morbidity and rates of grade ≥3 TEAEs. This study aimed to assess the safety of trastuzumab deruxtecan (DS‐8201) with a focus on interstitial lung disease and/or pneumonitis via the method of systematic review and single‐arm meta‐analysis. This comprehensive summary of the incidence of treatment‐emergent adverse events associated with DS‐8201 in clinical trials provides an important guide for clinicians. [ABSTRACT FROM AUTHOR]

Background: Pneumonia has a high incidence in traumatic brain injury (TBI) patients and lacks effective treatments. Early mobilization (EM) may be a potentially effective treatment. Aim: To explore the impact of EM on TBI‐related pneumonia in the neurosurgical intensive care unit (NICU). Study Design: This study was a historical control study. 100 TBI patients who received EM intervention were prospectively included as the experimental group (EM cohort), and 250 TBI patients were retrospectively included as the control group. The propensity score matching (PSM) method was employed to balance baseline and minimize potential bias. The relationship between EM and TBI‐related pneumonia was investigated by univariate and multivariate logistic regression, then further determined by subgroup analysis. The influence of other variables was excluded by interaction analyses. Finally, the effect of EM on the prognosis of TBI patients was analysed by comparing the Glasgow Coma Scale (GCS) and the hospital stay. Results: After screening, 86 patients were included in the EM cohort and 199 patients were included in the control cohort. There were obvious differences between the two cohorts at baseline, and these differences were eliminated after PSM, when the incidence of pneumonia was significantly lower in the EM cohort than in the control cohort (35.0% vs. 61.9%, p <.001). Multivariate logistic regression showed that EM was an independent risk factor for TBI‐related pneumonia and was significantly associated with a decreased incidence of pneumonia. This correlation was present in most subgroups and was not affected by other variables (p for interaction >.05). Patients in the EM cohort had shorter length of ICU stay (6 vs. 7 days, p =.017) and higher GCS at discharge (12 vs. 11, p =.010). Conclusion: EM is a safe and effective treatment for TBI patients in NICU, which can reduce the incidence of pneumonia, help to improve prognosis and shorten the length of ICU stay. Relevance to Clinical Practice: Although the utilization rate of EM is low in TBI patients for various reasons, EM is still an effective method to prevent complications. Our study confirms that a scientific and detailed EM strategy can effectively reduce the incidence of pneumonia while ensuring the safety of TBI patients, which is worthy of further research and clinical application. [ABSTRACT FROM AUTHOR]

SET domain‐containing 2 (SETD2) is a histone methyltransferase. It regulates the activity of H3K36me3 to enhance gene transcription. Macrophages (Mϕs) are one of the cell types involved in immune response. The purpose of this study is to clarify the role of SETD2 in regulating the immune property of Mϕ. The Mφs were isolated from the bronchoalveolar lavage fluid (BALF) and analysed through flow cytometry and RNA sequencing. A mouse strain carrying Mφs deficient in SETD2 was used. A mouse model of airway allergy was established with the ovalbumin/alum protocol. Less expression of SETD2 was observed in airway Mϕs in patients with allergic asthma. SETD2 of M2 cells was associated with the asthmatic clinical response. Sensitization reduced the expression of SETD2 in mouse respiratory tract M2 cells, which is associated with the allergic reaction. Depletion of SETD2 in Mφs resulted in Th2 pattern inflammation in the lungs. SETD2 maintained the immune regulatory ability in airway M2 cells. SETD2 plays an important role in the maintenance of immune regulatory property of airway Mφs. [ABSTRACT FROM AUTHOR]

This study investigated the roles of P‐selectin and Clara cell secretory protein 16 (CC16) levels in the pathogenesis of severe adenovirus (ADV) pneumonia in children and evaluated their ability to predict disease. Fifty‐one children (age, 1–5 years) with ADV pneumonia who were admitted to Xiamen Children's Hospital were included in this study and divided into the mild group (24 patients) and severe group (27 patients). A control group comprising healthy children of the same age who underwent routine physical examinations during the same period (30 patients) was also included. The univariate analysis demonstrated that the levels of the white blood cell count and C‐reactive protein, procalcitonin, d‐dimer, and P‐selectin were increased in a severe group compared with a mild group, while CC16 levels were significantly decreased (p < 0.05). The logistic regression analysis revealed that P‐selectin and CC16 levels were independent risk factors for severe ADV pneumonia in children. The areas under the ROC curves suggested that P‐selectin and CC16 exhibited high predictive value for severe ADV pneumonia. P‐selectin values more than 898.58 pg/mL and CC16 values less than 11.355 ng/mL predicted severe ADV pneumonia. P‐selectin and CC16 levels are correlated with the severity of ADV pneumonia in children. [ABSTRACT FROM AUTHOR]

Background: Complications are a practical consideration for elective magnetic resonance imaging (MRI) studies performed under general anaesthesia but relatively little is known about their distribution and risk factors. Objectives: To describe the incidence of complications associated with MRI performed under general anaesthesia at a large referral facility and evaluate potential risk factors for these complications. Study design: Retrospective case–control study. Methods: Patient information and details of the MRI procedure were collected retrospectively from medical records of all horses that had undergone an MRI under general anaesthesia at the University of Pennsylvania, New Bolton Center, between September 2005 and April 2012. Complications and categorical variables were examined by chi‐squared or Fisher's exact tests as appropriate. A mixed‐effects logistic regression approach was used to evaluate associations between explanatory variables and the outcome variable (complications or pyrexia). A univariable screen was used to select variables (likelihood ratio test p < 0.2) for inclusion in the multivariable analysis. Statistical significance was inferred when p ≤ 0.05. Results: Complications were noted after MRI in 51 (17.4%) of 293 events eligible for inclusion. Complications included pyrexia (n = 35), pneumonia (n = 14), colic (n = 10), facial/nerve paralysis (n = 6), diarrhoea (n = 4), and other (n = 3). The odds of developing a post‐anaesthetic complication were significantly decreased in horses that received peri‐anaesthetic antimicrobials (OR 0.29, 95% CI 0.14–0.63, p = 0.002). Increased age (OR 0.87, 95% CI, 0.76–0.99, p = 0.03) and peri‐anaesthetic antimicrobial administration (OR 0.23, 95% CI 0.08–0.65, p = 0.005) were associated with a decreased odds of developing pyrexia. Main limitations: Single centre retrospective design. Conclusions: Potential complications including pyrexia, pneumonia and colic should be recognised when pursuing MRI under general anaesthesia. The administration of peri‐anaesthetic antimicrobials decreased the odds of a complication and warrants consideration, particularly in horses that might be classified as high risk. [ABSTRACT FROM AUTHOR]

Pneumonia is a serious and life‐threatening lung inflammation with high morbidity and mortality. Accumulating evidence has suggested that esculin, a derivative of coumarin, possesses potent anti‐inflammatory effects. This study is designed to explore the pharma role and underlying mechanism of esculin against lipopolysaccharides (LPS)‐induced pneumonia. TC‐1 cells were stimulated by LPS to mimic the inflammatory injury model in vitro. Cell viability, proliferation, and apoptosis were determined using MTT assay, 5‐ethynyl‐2′‐deoxyuridine assay, and flow cytometry. Interleukin‐1β and tumor necrosis factor α levels were analyzed using an enzyme‐linked immunosorbent assay. Reactive oxygen species and superoxide dismutase were examined using special assay kits. Macrophage polarization was detected using flow cytometry. Mitogen‐activated protein kinase 14 (MAPK14) level was detected by real‐time quantitative polymerase chain reaction. MAPK14 and ubiquitin‐specific protease 7 (USP7) protein levels were determined using western blot assay. After Ubibrowser database prediction, the interaction between USP7 and MAPK14 was verified using a Co‐immunoprecipitation assay. The biological role of esculin was verified in LPS‐challenged ALI mice in vivo. Here, we found that esculin significantly relieved LPS‐induced TC‐1 cell proliferation inhibition, and apoptosis, inflammatory response, oxidative stress, and M1‐type macrophage polarization promotion. MAPK14 and USP7 expressions were enhanced in LPS‐treated TC‐1 cells, which was partly abolished by esculin treatment. Overexpressing MAPK14 attenuated the repression of esculin on LPS‐triggered TC‐1 cell injury. At the molecular level, USP7 interacted with MAPK14 and maintained its stability by removing ubiquitin. Moreover, esculin repressed the progression of pneumonia in vivo by regulating MAPK14. Taken together, esculin exposure could mitigate LPS‐induced TC‐1 cell injury partly by targeting the USP7/MAPK14 axis, providing a better understanding of the role of esculin in the anti‐inflammatory therapeutics for pneumonia. Esculin treatment could relieve LPS‐induced TC‐1 cell proliferation inhibition, and apoptosis, inflammation, oxidative stress, macrophage M1 polarization promotion in vitro, as well as pneumonia progression in vivo by regulating the USP7/mitogen‐activated protein kinase 14 (MAPK14) axis. Furthermore, USP7 could facilitate protein stability and MAPK14 expression in TC‐1 cells. [ABSTRACT FROM AUTHOR]

Summary: Pneumonia disease progress rapidly leading to missed diagnosis and diagnosis error. However, it is significant to be diagnosed accurately as well as adopted timely treatments, particularly for children and elderly people over 65. In the first place, we propose a novel method for data augmentation to expand non‐case samples in order to solve the problem of imbalance of the raw data. Then we have designed a neural network based on separable convolution layers, using deep learning to classify between Pneumonia cases and normal cases from chest X‐ray images. Finally, well‐known performance measures are utilized to evaluate our model, obtaining the following results: Accuracy (0.97), AUC (0.99), Sensitivity (0.98), Specificity (0.98), Precision (0.95), F1‐Score (0.97), and Youden Index (0.90). Simultaneously, we highlighted the proposed neural network recognition area via Class Activation Method for the purpose of providing an explainable diagnosis. Compared with the‐state‐of‐art models, our model performed better, and it may be regarded as an alternative in countries or regions lack of the relevant equipment and professional radiologists. [ABSTRACT FROM AUTHOR]

Summary Obstructive sleep apnea has been linked to an increased risk of pneumonia, possibly due to higher rates of nighttime aspirations. Few studies have directly investigated such aspirations in individuals with sleep apnea. This retrospective study included 142 adult patients with obstructive sleep apnea who underwent drug‐induced sedation endoscopy between 2017 and 2020. The incidence of penetrations and aspirations during the procedure was assessed, along with potential associated factors. The results showed that 28.1% of the patients experienced penetrations, 48.5% had aspirations, and 23.2% had neither. Male gender and epiglottic collapse were significantly associated with both penetrations and aspirations, while oropharyngeal collapse was more common in those without these events. This study highlights a high rate of aspirations during the procedure in individuals with sleep apnea, with epiglottic collapse and male gender identified as potential risk factors. These findings underscore the need for further research to understand the mechanisms of nighttime aspirations in sleep apnea and to develop targeted strategies to reduce pneumonia risk in this population. [ABSTRACT FROM AUTHOR]

Background: Parenteral penicillin G (PENG) and oral amoxicillin (AMOX) are recommended as treatment for pediatric community‐acquired pneumonia (CAP). With recent epidemiologic penicillin susceptibility data for Streptococcus pneumoniae, the most common etiology of CAP, the objective of this study was to evaluate optimal dosing regimens of PENG and AMOX based on population pharmacokinetics linked to current susceptibility data. Methods: Using NONMEM v7.3, Monte Carlo simulations (N = 10,000) were conducted for AMOX 15 mg/kg/dose PO every 8 h (standard‐dose), AMOX 45 mg/kg/dose PO every 12 h (high‐dose), and PENG 62,500 units/kg/day IV every 6 h using six virtual subjects with ages spanning 3 months to 15 years old. The probability of target attainment (PTA) was determined for both serum and epithelial lining fluid (ELF) to achieve free drug concentrations above the minimum inhibitory concentration (%fT>MIC) across the population of pneumococci for 30%–50% of the dosing interval. Results: In 2018, all 21 (100%) pneumococcal isolates were susceptible to both PENG and AMOX based on Clinical and Laboratory Standards Institute (CLSI; MIC at 2 mg/L) breakpoints, and 15 of 21 (71%) were susceptible based on EUCAST (MIC at 0.5 mg/L) breakpoints. As compared to CLSI, EUCAST breakpoints consistently achieved higher PTA for all antibiotic regimens. At 50% fT>MIC in the serum at the susceptible MICs, standard‐dose AMOX achieved >4% PTA (CLSI) and >86% PTA (EUCAST); high‐dose AMOX achieved >73% PTA (CLSI) and >99% PTA (EUCAST); and PENG achieved 0% PTA (using CLSI) and 100% PTA (using EUCAST). Standard‐dose AMOX, high‐dose AMOX, and PENG achieved >71%, >93%, and 100% PTA, respectively, in the serum at 30%–50% fT>MIC when each patient was stochastically linked to an MIC based on the frequency distribution of national susceptibility data. The PTA was consistently lower in ELF as compared with serum for all regimens. Conclusion: Based on the recent rates of resistance, antibiotic doses evaluated provide appropriate exposure for pediatric CAP based on the serum and ELF data associated with predicted clinical and microbiologic success for pneumococcus. High‐dose AMOX may still be required to treat pediatric CAP, especially if using CLSI breakpoints. Ongoing surveillance for resistance is essential. [ABSTRACT FROM AUTHOR]

Background and Objective: The identification of factors associated with long‐term prognosis after community‐onset pneumonia in elderly patients should be considered when initiating advance care planning (ACP). We aimed to identify these factors and develop a prediction score model. Methods: Patients aged 65 years and older, who were hospitalized for pneumonia at nine collaborating institutions, were included. The prognosis of patients 180 days after the completion of antimicrobial treatment for pneumonia was prospectively collected. Results: The total number of analysable cases was 399, excluding 7 outliers and 42 cases with missing data or unknown prognosis. These cases were randomly divided in an 8:2 ratio for score development and testing. The median age was 82 years, and there were 68 (17%) deaths. A multivariate analysis showed that significant factors were performance status (PS) ≥2 (Odds ratio [OR], 11.78), hypoalbuminemia ≤2.5 g/dL (OR, 5.28) and dementia (OR, 3.15), while age and detection of antimicrobial‐resistant bacteria were not associated with prognosis. A scoring model was then developed with PS ≥2, Alb ≤2.5, and dementia providing scores of 2, 1 and 1 each, respectively, for a total of 4. The area under the curve was 0.8504, and the sensitivity and specificity were 94.6% and 61.7% at the cutoff of 2, respectively. In the test cases, the sensitivity and specificity were 91.7% and 63.1%, respectively, at a cutoff value of 2. Conclusion: Patients meeting this score should be considered near the end of life, and the initiation of ACP practices should be considered. We aimed to identify factors influencing the long‐term prognosis of elderly patients with pneumonia and to develop a prediction score model for the effective initiation of advance care planning. Performance status (PS) ≥2, hypoalbuminemia ≤2.5 g/dL and dementia were significant factors. The scoring model demonstrated 94.6% sensitivity and 61.7% specificity. [ABSTRACT FROM AUTHOR]

Background: Pneumonia is a leading diagnosis for patients requiring critical care. Prediction of the causal organisms has proved challenging, and antibiotic overuse is a burning issue. Objective: This study aimed to compare the results of the BioFire FilmArray Pneumonia Panel (PN Panel) to standard diagnostic methods and evaluate its potential impact in an intensive care unit (ICU). Methods: This is a retrospective study including adult patients admitted to the ICUs with a diagnosis of pneumonia. The agreement between the PN panel results and the standard diagnostic method was analyzed. Actual and potential adjustments of antimicrobials after the PN panel results were reviewed and compared. Results: Two hundred ninety three patients with pneumonia were included. The PN panel identified at least one pathogen in 159 specimens (54.2%), while the standard diagnostic method identified at least one pathogen in 132 specimens (45.0%). Positive percentage agreement between the PN panel and standard‐of‐care culture reached 94%, and negative percentage agreement reached 97%. Among 293 patients, the availability of PN results led to escalation of antimicrobials in 38 (19%) patients and de‐escalation or discontinuation of antimicrobials in 95 (32.4%) patients. Conclusion: This pilot study showed the PN panel could provide accurate results on the causative pathogens and detect resistant bacteria. It could reduce the use of broad‐spectrum antibiotics and overall antibiotic use. If the PN panel could be checked at the emergency department, targeted antibiotics could be administered when the patient arrived at the ICU. [ABSTRACT FROM AUTHOR]

Background: The incidence of atypical pneumonia among immunocompromised patients is not well characterized. Establishing a diagnosis of atypical pneumonia is challenging as positive tests must be carefully interpreted. We aimed to assess the test positivity rate and incidence of atypical pneumonia in transplant recipients. Methods: A retrospective cohort study was conducted at the Yale New Haven Health System in Connecticut. Adults with solid organ transplant, hematopoietic stem cell transplant (HSCT), or chimeric antigen receptor T‐cell, who underwent testing for atypical pathogens of pneumonia (Legionella pneumophilia, Mycoplasma pneumoniae, Chlamydia pneumoniae, and Bordetella pertussis) between January 2016 and August 2022 were included. Positive results were adjudicated in a clinical context using pre‐defined criteria. A cost analysis of diagnostic testing was performed. Results: Note that, 1021 unique tests for atypical pathogens of pneumonia were performed among 481 transplant recipients. The testing positivity rate was 0.7% (n = 7). After clinical adjudication, there were three cases of proven Legionella and one case of possible Mycoplasma infection. All cases of legionellosis were in transplant recipients within 1‐year post‐transplantation with recently augmented immunosuppression and lymphopenia. The possible case of Mycoplasma infection was in an HSCT recipient with augmented immunosuppression. The cost of all tests ordered was $50,797.73. Conclusion: The positivity rate of tests for atypical pneumonia was very low in this transplant cohort. An algorithmic approach that targets testing for those with compatible host, clinical, radiographic, and epidemiologic factors, and provides guidance on test selection and test interpretation, may improve the diagnostic yield and lead to substantial cost savings. [ABSTRACT FROM AUTHOR]

Key Clinical Message: Necrotizing pneumonia (NP) is the destruction of the interstitial part of the lung due to severe infection. One cause of this rare and fatal condition in pediatrics is Acinetobacter. Severe infections, especially pneumonia, can prone pediatric patients to ischemic stroke. This study reports an 8‐year‐old girl presented to the emergency department complaining of shortness of breath, fever, and fatigue. She was admitted to the intensive care unit due to respiratory distress and pericardial effusion. Swab and respiratory secretion tests for COVID‐19 and Acinetobacter were positive. In her admission course, her condition deteriorated, and on the fifth day, she underwent a craniotomy due to the signs of increased intracranial pressure (ICP). The computed tomography (CT) scan showed an ischemic stroke. Despite all efforts and medical efforts, the patient's clinical condition got worse, and she died 10 days after the surgery. COVID‐19 can lead to vulnerability to severe bacterial infections such as NP in pediatrics. Severe infections are a significant risk factor for ischemic stroke. The presentation might be different in intubated unconscious patients, such as detecting increased ICP signs. In severe and extensive cases of NP and ischemia, the destruction of the lungs and brain tissue might be irreversible and even lethal. Doctors and parents should consider neurologic complaints in children with infectious diseases as a serious issue since infections make children vulnerable to complications such as stroke. [ABSTRACT FROM AUTHOR]

Background: Pneumonia is typically caused by a variety of pathogenic microorganisms. Traditional research often focuses on the infection of a few microorganisms, whereas metagenomic studies focus on the impact of the bacteriome and mycobiome on respiratory diseases. Reports on the virome characteristics of pediatric pneumonia remain relatively scarce. Methods: We employed de novo assembly and combined homology‐ and feature‐based methods to characterize the respiratory virome in whole‐genome DNA sequencing samples from oropharynx (OP) swabs, nasopharynx (NP) swabs, and bronchoalveolar lavage fluids (BALF) of children with pneumonia. Results: Significant differences were observed in the alpha and beta diversity indexes, as well as in the composition of the oropharyngeal virome, between pneumonia cases and controls. We identified 1137 viral operational taxonomic units (vOTUs) with significant differences, indicating a preference of pneumonia‐reduced vOTUs for infecting Prevotella, Neisseria, and Veillonella, whereas pneumonia‐enriched vOTUs included polyomavirus, human adenovirus, and phages targeting Staphylococcus, Streptococcus, Granulicatella, and Actinomyces. Comparative analysis revealed higher relative abundances and prevalence rates of pneumonia‐enriched OP vOTUs in NP and BALF samples compared to pneumonia‐reduced vOTUs. Additionally, virome analysis identified six pediatric patients with severe human adenovirus or polyomavirus infections, five of whom might have been undetected by targeted polymerase chain reaction (PCR)‐based testing. Conclusions: This study offers insights into pediatric pneumonia respiratory viromes, highlighting frequent transmission of potentially pathogenic viruses and demonstrating virome analysis as a valuable adjunct for pathogen detection. [ABSTRACT FROM AUTHOR]

Background: The inhalation of paraquat (PQ), one of the most widely used herbicides in the world, can result in lung injury. Curcuma longa (Cl) has long history in traditional and folk medicine for the treatment of a wide range of disorders including respiratory diseases. Aim: The aim of the present work was to evaluate the preventive effect of Cl on inhaled PQ‐induced lung injury in rats. Methods: Male Wistar rats were divided into 8 groups (n = 7), one group exposed to saline (control) and other groups exposed to PQ aerosol. Saline (PQ), Cl extract, (two doses), curcumin (Cu), pioglitazone (Pio), and the combination of Cl‐L + Pio and dexamethasone (Dex) were administered during the exposure period to PQ. Total and differential white blood cell (WBC) counts, oxidant and antioxidant indicators in the bronchoalveolar lavage (BALF), interleukin (IL)‐10, and tumor necrosis alpha (TNF‐α) levels in the lung tissues, lung histologic lesions score, and air way responsiveness to methacholine were evaluated. Results: WBC counts (Total and differential), malondialdehyde level, tracheal responsiveness (TR), IL‐10, TNF‐α and histopathological changes of the lung were markedly elevated but total thiol content and the activities of catalase and superoxide dismutase were decreased in the BALF in the PQ group. Both doses of Cl, Cu, Pio, Cl‐L + Pio, and Dex markedly improved all measured variables in comparison with the PQ group. Conclusion: CI, Pio, and Cl‐L + Pio improved PQ‐induced lung inflammation and oxidative damage comparable with the effects of Dex. [ABSTRACT FROM AUTHOR]

Objective: Positive antineutrophil cytoplasmic antibodies (ANCAs) may occur in the setting of interstitial lung disease (ILD), with or without ANCA‐associated vasculitis (AAV). We aim to compare the characteristics and clinical course of patients with ILD and positive ANCA (ANCA‐ILD) to those with negative ANCA. Methods: We performed a single‐center retrospective cohort study from 2018 to 2021. All patients with ILD and ANCA testing were included. Patient characteristics (symptoms, dyspnea scale, and systemic AAV), test results (pulmonary high‐resolution computed tomography and pulmonary function tests), and adverse events were collected from electronic medical records. Descriptive statistics and the Fisher exact test were used to compare the outcomes of patients with ANCA‐ILD to those with ILD and negative ANCA. Results: A total of 265 patients with ILD were included. The mean follow‐up duration was 69.3 months, 26 patients (9.8%) were ANCA positive, and 69.2% of those with ANCA‐ILD had another autoantibody. AAV occurred in 17 patients (65.4%) with ANCA‐ILD. In 29.4% of patients, AAV developed following ILD diagnosis. Usual interstitial pneumonia was the most common radiologic pattern in patients with ANCA‐ILD. There was no association between ANCA status and the evolution of dyspnea, diffusing capacity of the lungs for carbon monoxide, and lung imaging. Forced vital capacity improved over time in 42% of patients with ANCA‐ILD and in 17% of patients with negative ANCA (P = 0.006). Hospitalization occurred in 46.2% of patients with ANCA‐ILD and in 21.8% of patients with negative ANCA (P = 0.006). Both groups had similar mortality rates. Conclusion: Routine ANCA testing should be considered in patients with ILD. Patients with ANCA‐ILD are at risk for AAV. More research is required to better understand and manage patients with ANCA‐ILD. [ABSTRACT FROM AUTHOR]

Background: The efficacy of anti‐CTLA‐4 antibody (ipilimumab) plus anti‐programmed cell death 1 antibody (nivolumab) in treating advanced non‐small cell lung cancer (NSCLC) is impeded by an elevated risk of severe immune‐related adverse events. However, our understanding of associations among pre‐existing fibrosis, emphysematous changes, and objective indicators as predictive factors is limited for severe pneumonitis in NSCLC patients receiving this combination therapy. Thus, we retrospectively investigated these associations, including overall tumor burden, before treatment initiation in the Japanese population. Methods: We focused on patients (n = 76) with pre‐existing interstitial lung disease (ILD) to identify predictors of severe pneumonitis. Variables included age, sex, smoking status, programmed cell death ligand 1 expression, overall tumor burden, chest computed tomography‐confirmed fibrosis, serum markers, and respiratory function test results. Results: Severe pneumonitis was more frequent in patients with squamous cell carcinoma, fibrosis, low diffusing capacity for carbon monoxide (%DLCO), and high surfactant protein D (SP‐D) level. Notably, squamous cell carcinoma, baseline %DLCO, and SP‐D level were significant risk factors. Our findings revealed the nonsignificance of tumor burden (≥85 mm) in predicting severe pneumonitis, emphasizing the importance of pre‐existing ILD. Conversely, in cases without pre‐existing fibrosis, severe pneumonitis was not associated with %DLCO or SP‐D level (93.2% vs. 91.9%, and 63.3 vs. 40.9 ng/mL, respectively) and was more common in patients with a large overall tumor burden (97.5 vs. 70.0 mm). Conclusion: Vigilant monitoring and early intervention are crucial for patients with squamous cell carcinoma, high SP‐D level, or low %DLCO undergoing ipilimumab plus nivolumab therapy. [ABSTRACT FROM AUTHOR]