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Background: Sepsis is a leading cause of mortality in intensive care units (ICUs). Cell-free hemoglobin (CFH) released during sepsis interacts with lysosomal enzymes from neutrophils and macrophages. This study aims to examine the association of LVV-hemorphin-7 (LVV-H7), cathepsin D, and cathepsin G with sepsis and shock in ICU patients. Methods: A prospective observational cohort study was conducted in the medical ICU of a tertiary referral hospital in Taiwan. The patients with an acute increasing sequential organ failure assessment (SOFA) score ≥ 2 between 2022 and 2023. Blood samples from 40 healthy controls were obtained from the hospital biobank. CFH metabolites, including LVV-H7 and lysosomal enzyme cathepsin D and cathepsin G, were compared between the sepsis (definite and probable) and non-sepsis (possible sepsis) groups. Multivariate logistic regression analyzed factors associated with sepsis and shock. Results: Among 120 patients, 75 were classified as septic and 45 as non-septic. Significant differences were observed in CFH, cathepsin D, cathepsin G, and LVV-H7 levels between sepsis and non-sepsis groups. LVV-H7 was a significant predictor for sepsis (adjusted OR [aOR] 1.009, 95% CI 1.005–1.013; p < 0.001) and shock (aOR 1.005, 95% CI 1.002–1.008; p < 0.05). Cathepsin G predicted non-shock (aOR 0.917, 95% CI 0.848–0.991; p < 0.05), while cathepsin D predicted septic shock (aOR 1.001, 95% CI 1.000–1.002; p < 0.05). Conclusions: LVV-H7, cathepsin D, and cathepsin G are associated with the classification of sepsis and shock episodes in critically ill patients with elevated SOFA scores. [ABSTRACT FROM AUTHOR]

Sepsis causes systemic inflammatory responses and acute lung injury (ALI). Despite modern treatments, sepsis‐related ALI mortality remains high. Aqueous extract of Descuraniae Semen (AEDS) exerts anti‐endoplasmic reticulum (ER) stress, antioxidant and anti‐inflammatory effects. AEDS alleviates inflammation and oedema in ALI. Sodium‐potassium‐chloride co‐transporter isoform 1 (NKCC1) is essential for regulating alveolar fluid and is important in ALI. The NKCC1 activity is regulated by upstream with‐no‐lysine kinase‐4 (WNK4) and STE20/SPS1‐related proline/alanine‐rich kinase (SPAK). This study aimed to investigate the effects of AEDS on lipopolysaccharide (LPS)‐induced ALI model in A549 cells, considering the regulation of ER stress, WNK4‐SPAK‐NKCC1 cascades, inflammation and apoptosis. Cell viability was investigated by the CCK‐8 assay. The expressions of the proteins were assessed by immunoblotting analysis assays. The levels of pro‐inflammatory cytokines were determined by ELISA. The expression of cytoplasmic Ca2+ in A549 cells was determined using Fluo‐4 AM. AEDS attenuates LPS‐induced inflammation, which is associated with increased pro‐inflammatory cytokine expression and activation of the WNK4‐SPAK‐NKCC1 pathway. AEDS inhibits the WNK4‐SPAK‐NKCC1 pathway by regulating of Bcl‐2, IP3R and intracellular Ca2+. WNK4 expression levels are significantly higher in the WNK4‐overexpressed transfected A549 cells and significantly decrease after AEDS treatment. AEDS attenuates LPS‐induced inflammation by inhibiting the WNK4‐SPAK‐NKCC1 cascade. Therefore, AEDS is regarded as a potential therapeutic agent for ALI. [ABSTRACT FROM AUTHOR]

Background and Objective: This study evaluated the predictive roles of hematologic inflammatory biomarkers including neutrophil‐percentage‐to‐albumin ratio (NPAR), neutrophil‐to‐lymphocyte ratio (NLR) and eosinophil‐to‐lymphocyte ratio (ELR) for mortality in community‐dwelling individuals with chronic obstructive pulmonary disease (COPD). Methods: This longitudinal study extracted data of adults 40–79 years who had physician‐diagnosed COPD from the United States (US) National Health and Nutrition Examination Survey (NHANES) 1999–2018. Cox regressions determined the associations between NPAR, NLR, ELR and their components, with all‐cause mortality, cardiovascular disease (CVD) mortality and mortality from chronic lower respiratory disease (CLRD). Receiver operating characteristic (ROC) curve analysis estimated the predictive performances of these biomarkers for 5‐year all‐cause mortality. Results: Data of 1158 subjects were analysed. After adjustment, higher NPAR was significantly associated with increased all‐cause and CVD mortality, and mortality from CLRD (adjusted hazard ratio [aHR] = 1.14, 1.15 and 1.16). Higher NLR was associated with an increased all‐cause and CVD mortality (aHR = 1.16 and 1.29). Higher neutrophil was associated with increased all‐cause mortality and mortality from CLRD (aHR = 1.13 and 1.34). Albumin was associated with decreased all‐cause and CVD mortality (aHR = 0.91 and 0.86). ELR, eosinophil or lymphocyte was not significantly associated with either mortality outcomes. Adjusted AUC of NPAR and NLR in predicting 5‐year all‐cause mortality were 0.808 (95% CI: 0.722–0.845) and 0.799 (95% CI: 0.763–0.835), respectively. Conclusion: In community‐dwelling US adults with COPD, increased NPAR and NLR are associated with mortality risks. NPAR outperforms the other hematologic inflammatory biomarkers in predicting 5‐year all‐cause mortality. Easy‐to‐use accurate predictors of chronic obstructive pulmonary disease (COPD) prognosis are important. Data from community‐dwelling adults with COPD in the United States were analysed to investigate associations and predictive values of several biomarkers derived from routine blood samples. Neutrophil‐percentage‐to‐albumin (NPAR) ratio appeared to be the best indicator of mortality in these patients. See relatededitorial [ABSTRACT FROM AUTHOR]

Background: Patients with chronic obstructive pulmonary disease (COPD) often have exercise intolerance. The prevalence of hypertension in COPD patients ranges from 39–51%, and β-blockers and amlodipine are commonly used drugs for these patients. Objectives: We aimed to study the impact of β-blockers and amlodipine on cardiopulmonary responses during exercise. Methods: A total 81 patients with COPD were included and the patients underwent spirometry, cardiopulmonary exercise tests, and symptoms questionnaires. Results: There were 14 patients who took bisoprolol and 67 patients who did not. Patients with COPD taking ß-blockers had lower blood oxygen concentration (SpO2) and more leg fatigue at peak exercise but similar exercise capacity as compared with patients not taking bisoprolol. There were 18 patients treated with amlodipine and 63 patients without amlodipine. Patients taking amlodipine had higher body weight, lower blood pressure at rest, and lower respiratory rates during peak exercise than those not taking amlodipine. Other cardiopulmonary parameters, such as workload, oxygen consumption at peak exercise, tidal volume at rest or exercise, cardiac index at rest or exercise were not significantly different between patients with or without bisoprolol or amlodipine. Smoking status did not differ between patients with or without bisoprolol or amlodipine. Conclusions: COPD is often accompanied by hypertension, and β-blockers and amlodipine are commonly used antihypertensive drugs for these patients. Patients with COPD taking bisoprolol had lower SpO2 and more leg fatigue during peak exercise. Patients taking amlodipine had lower respiratory rates during exercise than those not taking amlodipine. Exercise capacity, tidal volume, and cardiac index during exercise were similar between patients with and without bisoprolol or amlodipine. [ABSTRACT FROM AUTHOR]

Nuss surgery is effective in correcting pectus excavatum (PE), with a recurrence rate of 1.2–27%. Re-do surgery is successful but still has a 6% failure rate. Patients with obstructive sleep apnea (OSA) experience repetitive PE-associated sternal depression during sleep. As the prevalence of OSA among PE patients is higher than the average, co-existing OSA in PE patients might negatively affect the efficacy of Nuss surgery. This study aimed to evaluate the impact of co-existing OSA on Nuss surgery in patients with PE. In total, 20 adult patients with PE only and 9 patients with PE and OSA were analyzed. Polysomnography was performed before Nuss surgery to evaluate OSA. Sternovertebral distance (SVD) and radiographic Haller index (RHI) were recorded before surgery and at 3, 6, and 24 months postoperatively. The results showed that percentage changes in SVD in patients with PE only at 3, 6, and 24 months postoperatively were significantly increased compared with those in the patients with PE and OSA (31.1% vs. 14.1% at 3 months; 37.5% vs. 21.4% at 6 months; 42.5% vs. 19.2% at 24 months). Meanwhile, percentage changes in RHI were significantly lower in patients with PE alone than in the patients with PE and OSA (-22.9% vs. -9.3% at 3 months; -27.9% vs. -18.7% at 6 months; -30.6% vs. -16.7% at 24 months). This study showed that co-existing OSA might reduce the efficacy of Nuss surgery for patients with PE. We recommend that patients with PE should be evaluated and treated for OSA before surgery to prevent surgical failure after bar removal. [ABSTRACT FROM AUTHOR]

Background: The decision guild for non-invasive positive pressure ventilation (NPPV) application in acute respiratory failure (ARF) patients still needs to work out. Methods: Adult patients with acute hypoxemic or hypercapnic respiratory failure were recruited and treated with NPPV or primary invasive mechanical ventilation (IMV). Patients' characteristic and clinical outcomes were recorded. Logistic regression models were used to estimate the adjusted odds ratio (aOR) and 95% confidence intervals for baseline characteristics and clinical outcomes. Subgroup analyses by reason behind successful NPPV were conducted to ascertain if any difference could influence the outcome. Results: A total of 4525 ARF patients were recruited in our facility between year 2015 and 2017. After exclusion, 844 IMV patients, 66 patients with failed NPPV, and 74 patients with successful NPPV were enrolled. Statistical analysis showed APACHE II score (aOR = 0.93), time between admission and start NPPV (aOR = 0.92), and P/F ratio (aOR = 1.04) were associated with successful NPPV. When comparing with IMV patients, failed NPPV patients displayed a significantly lower APACHE II score, higher Glasgow Coma Scale, longer length of stay in hospital, longer duration of invasive ventilation, RCW/Home ventilator, and some comorbidities. Conclusion: APACHE II score, time between admission and start NPPV, and PaO2 can be predictors for successful NPPV. The decision of NPPV application is critical as ARF patients with failed NPPV have various worse outcomes than patients receiving primary IMV. [ABSTRACT FROM AUTHOR]

Background: Lung adenocarcinoma is a common disease with a high mortality rate. Epidermal growth factor receptor (EGFR) mutations are found in adenocarcinomas, and oral EGFR-tyrosine kinase inhibitors (EGFR-TKIs) show good responses. EGFR-TKI therapy eventually results in resistance, with the most common being T790M. T790M is also a biomarker for predicting resistance to first- and second-generation EGFR-TKIs and is sensitive to osimertinib. The prognosis was better for patients with acquired T790M who were treated with osimertinib than for those treated with chemotherapy. Therefore, T790M mutation is important for deciding further treatment and prognosis. Previous studies based on small sample sizes have reported very different T790 mutation rates. We conducted a meta-analysis to evaluate the T790M mutation rate after EGFR-TKI treatment. Methods: We systematic reviewed the electronic databases to evaluate the T790M mutation rate after treatment with first-generation (gefitinib, erlotinib, and icotinib) and second-generation (afatinib and dacomitinib) EGFR-TKIs. Random-effects network meta-analysis and single-arm meta-analysis were conducted to estimate the T790M mutation rate of the target EGFR-TKIs. Results: A total of 518 studies were identified, of which 29 were included. Compared with afatinib, a higher odds ratio (OR) of the T790M mutation rate was observed after erlotinib [OR = 1.48; 95% confidence interval (CI):1.09–2.00] and gefitinib (OR = 1.45; 95% CI: 1.11–1.90) treatments. An even OR of the T790M mutation rate was noted after icotinib treatment (OR = 0.91, 95% CI: 0.46–1.79) compared with that after afatinib. The T790M mutation rate was significantly lower with afatinib (33%) than that with gefitinib (49%) and erlotinib treatments (47%) (p < 0.001). The acquired T790M mutation rate in all participants was slightly lower in Asians (43%) than that in Caucasians (47%). Conclusions: Erlotinib and gefitinib had a higher OR for the T790M mutation than afatinib. The T790M mutation rate was significantly lower in afatinib than in gefitinib and erlotinib. T790M is of great significance because osimertinib shows a good prognosis in patients with T790M mutation. Systematic Review Registration: PROSPERO, identifier CRD42021257824. [ABSTRACT FROM AUTHOR]

Acute lung injury (ALI) is often characterized by severe lung inflammation and pulmonary edema with poor gas exchange and hypoxemia. Alveolar inflammation and water flooding are, in fact, notable features of ALI pathogenesis. The sodium-potassium-chloride co-transporter isoform 1 (NKCC1), localized at the basolateral surface of the lung epithelium, drives water transport via back transport of Na+ and Cl− to the alveolar air space. NKCC1, therefore, is crucial in regulating alveolar fluid. Increased expression of NKCC1 results in increased alveolar fluid secretion and impaired alveolar fluid clearance. During ALI, the with no lysine kinase (WNK), oxidative stress responsive kinase 1 (OSR1), and STE20/SPS1-related proline/alanine-rich kinase (SPAK) pathways are activated, which upregulates NKCC1 expression. Proinflammatory cytokines also enhance the expression of NKCC1 via c-Jun N-terminal kinase-and p38-dependent pathways. NKCC1 activation also increases the expression of proinflammatory cytokines via cell rupture and activation of macrophages. Increased proinflammatory cytokines, in turn, recruit inflammatory cells to the site of injury and cause further lung damage. Animals with high expression of NKCC1 show more severe lung injury with presentations of more severe pulmonary edema and microvascular permeability, higher expression of proinflammatory cytokines, and greater neutrophilic infiltration. In contrast, animals with low expression of NKCC1 or those treated with NKCC1 inhibitors show less severe lung injury with milder levels of presentations of ALI. These reports collectively highlight a novel role of NKCC1 in ALI pathogenesis. Manipulation of NKCC1 expression levels could, therefore, represent novel modalities for effective ALI treatment. [ABSTRACT FROM AUTHOR]