Correlating Reiff scores with clinical, functional, and prognostic factors: characterizing noncystic fibrosis bronchiectasis severity: validation from a nationwide multicenter study in Taiwan.

BACKGROUND: Our study aimed to confirm a simplified radiological scoring system, derived from a modified Reiff score, to evaluate its relationship with clinical symptoms and predictive outcomes in Taiwanese patients with noncystic fibrosis bronchiectasis (NCFB). METHODS: This extensive multicenter retrospective study, performed in Taiwan, concentrated on patients diagnosed with NCFB verified through high-resolution computed tomography (HRCT) scans. We not only compared the clinical features of various types of bronchiectasis (cylindrical, varicose, and cystic). Furthermore, we established relationships between the severity of clinical factors, including symptom scores, pulmonary function, pseudomonas aeruginosa colonization, exacerbation and admission rates, and HRCT parameters using modified Reiff scores. RESULTS: Data from 2,753 patients were classified based on HRCT patterns (cylindrical, varicose, and cystic) and severity, assessed by modified Reiff scores (mild, moderate, and severe). With increasing HRCT severity, a significant correlation was found with decreased forced expiratory volume in the first second (FEV1) (p < 0.001), heightened clinical symptoms (p < 0.001), elevated pathogen colonization (pseudomonas aeruginosa) (p < 0.001), and an increased annual hospitalization rate (p < 0.001). In the following multivariate analysis, elderly age, pseudomonas aeruginosa pneumonia, and hospitalizations per year emerged as the only independent predictors of mortality. CONCLUSION: Based on our large cohort study, the simplified CT scoring system (Reiff score) can serve as a useful adjunct to clinical factors in predicting disease severity and prognosis among Taiwanese patients with NCFB.

Clinical effects of traditional Chinese herbal medicine management in patients with COVID-19 sequelae: A hospital-based retrospective cohort study in Taiwan.

Introduction: An estimated 43% of COVID-19 patients showed sequelae, including fatigue, neurocognitive impairment, respiratory symptoms, and smell or taste disorders. These sequelae significantly affect an individual's health, work capacity, healthcare systems, and socioeconomic aspects. Traditional Chinese herbal medicine (TCHM) management showed clinical benefits in treating patients with COVID-19 sequelae. This study aimed to analyze the effects of personalized TCHM management in patients with COVID-19 sequelae. Methods: After the COVID-19 outbreak in Taiwan, we recorded Chronic Obstructive Pulmonary Disease Assessment Tool (CAT), Chalder Fatigue Questionnaire (CFQ-11), and Brief Symptom Rating Scale (BSRS-5) to assess post-COVID respiratory, fatigue, and emotional distress symptoms, respectively. In this study, we retrospectively reviewed the medical records between July 2022 and March 2023. We analyzed the effects of TCHM administration after 14- and 28-days of treatment. Results: 47 patients were included in this study. The results demonstrated that personalized TCHM treatment significantly improved the CAT, CFQ-11, and BSRS-5 scores after 14 and 28 days. TCHM alleviated physical and psychological fatigue. In logistic regression analysis, there was no statistically significant differences in the severity of the baseline symptoms and TCHM administration effects concerning the duration since the initial confirmation of COVID-19, sex, age, or dietary preference (non-vegetarian or vegetarian). Conclusions: Our study suggested that personalized TCHM treatment notably reduced fatigue, respiratory and emotional distress symptoms after 14- and 28-days of treatment in patients with COVID-19 sequelae. We propose that TCHM should be considered as an effective intervention for patients with COVID-19 sequelae.

Pulmonary rehabilitation improves exercise capacity, health-related quality of life, and cardiopulmonary function in patients with non-small cell lung cancer.

BACKGROUND: Lung cancer significantly impairs exercise capacity and health-related quality of life (HRQL). Pulmonary rehabilitation (PR) has demonstrated positive effects on exercise capacity and HRQL in lung cancer patients. However, its impact on cardiopulmonary function needs further exploration. The aim of this study was to explore the effects of PR on cardiopulmonary function, exercise capacity and HRQL in patients with lung cancer. METHODS: Patients with lung cancer were enrolled in a 12-week PR program. Each participant underwent a thorough evaluation, which included spirometry, cardiopulmonary exercise testing, respiratory muscle strength test, and evaluation of HRQL using the Chronic Obstructive Pulmonary Disease Assessment Test (CAT). RESULTS: Fifty-six patients completed the PR program. Following PR, exercise capacity significantly improved, as evidenced by increased peak oxygen uptake and work rate (both p < 0.05). Exertional symptoms were notably reduced, including leg soreness and dyspnea at peak exercise, accompanied by a decrease in the CAT score (all p < 0.05). Furthermore, improvements in cardiopulmonary function were observed, encompassing respiratory muscle strength, ventilatory equivalent, tidal volume, stroke volume index, and cardiac index at peak exercise (all p < 0.05). CONCLUSIONS: PR demonstrated notable enhancements in cardiopulmonary function, exertional symptoms, exercise capacity, and HRQL in patients with lung cancer.

High-intensity aerobic exercise training improves exercise capacity, dyspnea, and fatigue in patients with severe asthma using triple inhaler.

Objectives: Asthma is a chronic respiratory disease that affects millions of people worldwide and causes severe symptoms such as wheezing, coughing, and breathing difficulty. Despite modern treatments, 3%-10% of patients develop severe asthma, which requires high-dose medications, and they may still experience frequent and severe symptoms, exacerbations, and psychological impacts. This study aimed to investigate the effects of high-intensity aerobic exercise training (HIAET) in patients with severe asthma. Materials and Methods: Patients with severe asthma were recruited, and cardiopulmonary exercise tests, dyspnea, and leg fatigue scores were performed before HIAET. Participants underwent a 12-week hospital-based HIAET, which involved exercising twice weekly to reach 80% of their peak oxygen uptake (VO2). Results: Eighteen patients with severe asthma underwent HIAET, which resulted in significant improvement in peak VO2 (1214.0 ± 297.9-1349.4 ± 311.2 mL/min, P = 0.004) and work rate (80.6 ± 21.2-96.2 ± 24.8 watt, P < 0.001) and decrease in dyspnea (5.1 ± 1.8-4.1 ± 1.2, P = 0.017) and fatigue scores (5.2 ± 2.3-4.0 ± 1.2, P = 0.020) at peak exercise. No significant changes were observed in spirometry results, respiratory muscle strength, or circulatory parameters. Conclusion: HIAET can lead to improved exercise capacity and reduced dyspnea and fatigue scores at peak exercise without changes in spirometry, respiratory muscle strength, and circulatory parameters.

Predictive role of neutrophil-percentage-to-albumin, neutrophil-to-lymphocyte and eosinophil-to-lymphocyte ratios for mortality in patients with COPD: Evidence from NHANES 2011-2018.

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.

Evaluation of the relationship of tricuspid regurgitation peak gradient/tricuspid annulus plane systolic excursion to exercise capacity, cardiac index, and ventilatory function during exercise in patients with COPD.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) often causes cardiopulmonary dysfunction, which deteriorates exercise capacity. Cardiopulmonary exercise testing (CPET) and echocardiography are common tools for evaluating cardiovascular function. No studies have analyzed the correlation between echocardiography-derived parameters and cardiopulmonary response during exercise. OBJECTIVES: We analyzed the correlation between echocardiographic parameters such as tricuspid regurgitation peak gradient (TRPG), tricuspid annular plane systolic excursion (TAPSE), TRPG/TAPSE and CPET-derived parameters. METHODS: Seventy-seven patients with COPD were evaluated. We analyzed the correlation between parameters derived from echocardiography, exercise capacity, cardiovascular and ventilatory parameters derived from CPET. RESULTS: The correlation between TRPG/TAPSE and work rate (WR) was moderate and negative (-0.4423, p = 0.0003), while TRPG had a weak negative correlation with WR (r= -0.3099, p = 0.0127). Oxygen uptake at peak exercise was weakly negatively correlated with TRPG/TAPSE (-0.3404, p = 0.0059), TRPG (r= -0.3123, p = 0.0120), and the ratio of early mitral inflow velocity to early mitral annular diastolic velocity (E/E'). The correlation between TRPG/TAPSE and exercise capacity was higher than that of TPRG, TAPSE, and E/E'. TRPG/TAPSE exhibited a moderate negative correlation with cardiac index, whereas TRPG and TAPSE showed a weak correlation. The correlation between TRPG/TAPSE and cardiac function during exercise was higher than that of TPRG, TAPSE, and E/E'. TRPG/TAPSE, TRPG, TAPSE, and E/E' were weakly negatively correlated with lung function. CONCLUSIONS: In assessing exercise capacity, cardiac function, and gas exchange, TRPG/TAPSE proves to be superior to other cardiac parameters. Higher TRPG/TAPSE levels corresponded to lower exercise capacity, cardiovascular and ventilatory function.

Early pulmonary rehabilitation of COVID-19 patients in an isolation ward and intensive care unit.

When patient with coronavirus disease 2019 (COVID-19) are hospitalized, the limited space for activity, disease itself causes fever, muscle aches, fatigue, respiratory failure with mechanical ventilation, or medications such as steroids or neuromuscular blocking can cause muscle dysfunction. Pulmonary rehabilitation (PR) should be arranged for these patients with COVID-19. However, the literature on early PR within 1 week of admission on patients with COVID-19 are limited. This review focuses on early PR in COVID-19 patients admitted to isolation wards or intensive care units. The essential components of early PR programs include education, breathing exercise, airway clearance, and physical activity training. Breathing exercises, including diaphragmatic and pursed-lip breathing, are known to improve lung function in chronic obstructive pulmonary disease and are also recommended for COVID-19 patients. Poor airway clearance can further aggravate pneumonia. Airway clearance techniques help patients to clear sputum and prevent the aggravation of pneumonia. Early physical activity training allows patients to maintain limb muscle function during hospitalization. It is recommended to design appropriate indoor exercise training for patients with frequency 1-2 times a day, and intensity should not be too high (dyspnea Borg Scale ≤3) in the acute stage. In order to achieve safe training, criteria for selecting stable patients and training termination are important. Early PR may help reduce the length of hospital stay, maintain functional status, improve symptoms of dyspnea, relieve anxiety, and maintain health-related quality of life in these patients after discharge.

Impact of bisoprolol and amlodipine on cardiopulmonary responses and symptoms during exercise in patients with chronic obstructive pulmonary disease.

BACKGROUND: Patients with chronic obstructive pulmonary disease (COPD) often have exercise intolerance. The prevalence of hypertension in COPD patients ranges from 39-51%, and ß-blockers and amlodipine are commonly used drugs for these patients. OBJECTIVES: We aimed to study the impact of ß-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 ß-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.

Investigating the differences in nutritional status between successfully weaned and unsuccessfully weaned respirator patients.

Long-term respirator users admitted to intensive care units need to be transferred to a respiratory care center (RCC) for weaning. It may cause malnutrition in critical care patients, which may manifest as a reduction in respiratory muscle mass, lower ventilatory capacity, and decreased respiratory tolerance. This study aimed to assess that if the patients' nutritional status were improved, it could help RCC patients to wean from respirators. All participants were recruited from the RCC of a medical foundation in the city and Taipei Tzu Chi Hospital. The indicators include serum albumin level, respirator detachment index, maximum inspiratory pressure (PImax), rapid shallow breathing index, and body composition measurements. We recorded the length of hospital stay, mortality, and RCW (respiratory care ward) referral rate for these participants and analyzed the differences in relevant research indicators between those who were and weren't weaned off. 43 of 62 patients were weaned from respirators, while 19 failed. The resuscitation rate was 54.8%. Patients with respirator weaning had a lower number of RCC admission days (23.1 ± 11.1 days) than respirator-dependent patients (35.6 ± 7.8 days, P < 0.05). The PImax of successfully weaned patients had a greater reduction (- 27.09 ± 9.7 cmH2O) than unsuccessful ones (- 21.4 ± 10.2 cmH2O, P < 0.05). The Acute Physiology and Chronic Health Evaluation II (APACHE II) scores of successfully weaned patients (15.8 ± 5.0) were lower than those who were not (20.4 ± 8.4, P < 0.05). There was no significant difference in serum albumin levels between the two groups. In the successfully weaned patients, the serum albumin concentration was increased from 2.2 ± 0.3 to 2.5 ± 0.4 mg/dL, P < 0.05. Improved nutritional status can help RCC patients to wean from respirators.

A real-world study of Afatinib plus ramucirumab in treatment-naïve, EGFR-mutated, non-small cell lung cancer.

BACKGROUND: Recent reports suggested combining ramucirumab with epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) to overcome EGFR resistance in non-small cell lung cancer (NSCLC). Nonetheless, evidence supporting the activity of afatinib and ramucirumab is lacking. This study investigated the survival benefits and safety profile of afatinib plus ramucirumab in patients with treatment-naïve, EGFR-mutated, metastatic NSCLC. MATERIALS AND METHODS: The medical records of patients with EGFR-mutated NSCLC were retrospectively retrieved. Patients who received first-line sequential afatinib followed by ramucirumab and the first-line combination of afatinib plus ramucirumab were included. The Kaplan-Meier was used to estimate the progression-free survival (PFS) of all included patients, patients on sequential afatinib followed by ramucirumab (PFS1), and patients on the up-front combination of afatinib and ramucirumab (PFS2). RESULTS: Thirty-three patients were included (25 women; median age: 63 [45-82] years). The median follow-up of the included patients was 17 months (range 6-89 months). the median PFS for the whole cohort was 71 months (95% CI 67.2-74.8) with eight events during the follow-up. The median PFS1 and PFS2 were 71 months (95 CI not defined) and 26 months (95% CI 18.6-33.4), respectively. In terms of OS, the median OS for all patients and patients on sequential treatment was not defined, while the median OS for patients on upfront combination was 30 months (95% CI 20.9-39.1). There was no significant association between EGFR mutation type and PFS1 or PFS2. CONCLUSIONS: Afatinib plus ramucirumab could improve the PFS of patients with EGFR-positive NSCLC at a predictable safety profile. Our data also suggest a survival benefit of adding ramucirumab to afatinib in patients with uncommon mutations, which should be investigated further.

The von Hippel-Lindau Tumor Suppressor Gene Mutations Modulate Lipocalin-2 Expression in Ferroptotic-Inflammatory Pathways.

A previous study of an animal model with tumor suppressor gene von Hippel-Lindau (VHL) conditional knockdown suggested that tissue inflammation and fibrosis play important roles in the development of clear-cell renal cell carcinoma (ccRCC), which is consistent with the epidemiological evidence linking inflammatory kidney disease and renal cancer. Ferroptosis and inflammation have been linked in a recent study, but the exact mechanism remains unclear. This study is aimed at investigating the mechanism of lipocalin-2- (LCN-2-) mediated ferroptosis and inflammation in vhl-mutated HK-2 cells and mouse primary proximal tubule cells (mRTCs) and the polarization of macrophage RAW 264.7 cells. Based on the levels of lipid reactive oxygen species (ROS) and the expression of glutathione peroxidase 4 (GPX4) in HK-2 cells, we observed that a VHL mutation increased ROS production and depressed GPX4 expression, whereas LCN-2 knockdown reversed these effects. Accordingly, VHL appears to affect ferroptosis in an LCN-2-dependent manner. We also revealed that LCN-2 sensitizes HK-2 cells to inflammation and macrophage RAW 264.7 cells to M1-like polarization. This study provides novel insights into the potential therapeutic target and strategy for attenuating the progression of ccRCC by revealing the role of VHL in regulating chronic inflammation within the LCN-2-ferroptosis pathway.

Co-existing obstructive sleep apnea reduces Nuss surgery efficacy in pectus excavatum.

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.

Transcriptome analysis in patients with asthma after inhaled combination therapy with long-acting ß2-agonists and corticosteroids.

Introduction: Asthma is one of the major public health problems that imposes a great burden on societal, financial, and healthcare around the world. Asthma poorly affects the health-related quality of life and daily activities of patients. Treatment of asthma, including inhaled corticosteroids (ICS) and long-acting beta-agonists (LABAs), mainly aims to improve the lung function and reduce symptoms and exacerbations. Current treatment regimens are symptom-based strategies, and the status of airway inflammation after treatment is yet unknown. We conducted this study to understand the comprehensive inflammation or airway remodeling status of patients after ICS-LABA treatment through RNA transcriptome analysis. Materials and methods: Eight newly diagnosed asthmatic patients and two healthy subjects were recruited in this study. Asthmatic patients underwent blood tests, lung function test, and RNA transcriptome analysis before and after ICS-LABA treatment. Results: In comparison with healthy subjects, pretreatment asthmatic patients had higher expression of protein tyrosine kinase and related signaling pathways. After ICS-LABA treatment, the expression of nuclear receptor transcription coactivator, N-acetyltransferase, protein tyrosine kinase, nuclear receptor, and RNA polymerase II-activating transcription factor were downregulated. However, the post-treatment asthmatic patients still had higher expression of cysteine-type endopeptidase, endodeoxyribonuclease, apolipoprotein, and unfolded protein was still upregulated than healthy subjects. Conclusions: The combination of ICS/LABAs decreased airway inflammatory and remodeling pathways. However, allergen stimulation-related pathways were still upregulated in patients after ICS/LABA treatment. The combination of medication and allergen removal is a complete strategy for asthma.

Emergent cesarean section in a preterm pregnant woman with severe COVID-19 pneumonia in Taiwan: A case report.

OBJECTIVE: The pandemic Coronavirus Disease 2019 (COVID-19) is a global public health crisis. Many maternity units worldwide are currently establishing the management protocols for these patients. CASE REPORT: We report the first critically ill pregnant woman with COVID-19-induced respiratory failure undergoing emergent caesarean delivery at 32 weeks of gestation, in the setting of a positive pressure operating room (OR) with negative pressure anteroom in Taiwan. CONCLUSION: Multidisciplinary planning and collaboration are necessary to achieve satisfactory clinical outcomes in pregnancies with critical COVID-19 pneumonia. The combinations of comprehensive evaluation, timely treatment as well as establishment of rigorous protocol and safe environment for the emergent delivery are important.

Factors and Outcomes Associated with Failed Noninvasive Positive Pressure Ventilation in Patients with Acute Respiratory Failure.

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.

Combinations of scalp acupuncture location for the treatment of post-stroke hemiparesis: A systematic review and Apriori algorithm-based association rule analysis.

Background: Post-stroke hemiparesis strongly affects stroke patients' activities of daily living and health-related quality of life. Scalp acupuncture (SA) is reportedly beneficial for post-stroke hemiparesis. However, there is still no standard of SA for the treatment of post-stroke hemiparesis. Apriori algorithm-based association rule analysis is a kind of "if-then" rule-based machine learning method suitable for investigating the underlying rules of acupuncture point/location selections. This study aimed to investigate the core SA combinations for the treatment of post-stroke hemiparesis by using a systematic review and Apriori algorithm-based association rule analysis. Methods: We conducted a systematic review to include relevant randomized controlled trial (RCT) studies investigating the effects of SA treatment in treating patients with post-stroke hemiparesis, assessed by the Fugl-Meyer Assessment (FMA) score. We excluded studies using herbal medicine or manual acupuncture. Results: We extracted 33 SA locations from the 35 included RCT studies. The following SA styles were noted: International Standard Scalp Acupuncture (ISSA), WHO Standard Acupuncture Point Locations (SAPL), Zhu's style SA, Jiao's style SA, and Lin's style SA. Sixty-one association rules were investigated based on the integrated SA location data. Conclusions: SAPL_GV20 (Baihui), SAPL_GV24 (Shenting), ISSA_MS6_i (ISSA Anterior Oblique Line of Vertex-Temporal, lesion-ipsilateral), ISSA_MS7_i (ISSA Posterior Oblique Line of Vertex-Temporal, lesion-ipsilateral), ISSA_PR (ISSA Parietal region, comprised of ISSA_MS5, ISSA_MS6, ISSA_MS7, ISSA_MS8, and ISSA_MS9), and SAPL_Ex.HN3 (Yintang) can be considered the core SA location combination for the treatment of post-stroke hemiparesis. We recommend a core SA combination for further animal studies, clinical trials, and treatment strategies.

Review of epidermal growth factor receptor-tyrosine kinase inhibitors administration to non-small-cell lung cancer patients undergoing hemodialysis.

Non-small-cell lung cancer (NSCLC) causes significant mortality worldwide. Patients with chronic renal failure have an increased risk of developing lung cancer. NSCLC Patients with chronic renal failure undergoing hemodialysis (HD) often exhibit poor performance, and chemotherapy is generally contraindicated. Oral epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) are effective treatment agents for NSCLC patients. However, the benefits and adverse effects of EGFR-TKIs in NSCLC undergoing HD are known. There are no clinical studies on the effects of EGFR-TKIs on NSCLC patients undergoing HD. We reviewed all previous case reports about EGFR-TKIs in NSCLC patients undergoing HD. It is difficult to design studies about the effects of EGFR-TKIs in patients undergoing HD, and this review is quite important. EGFR-TKIs are well tolerated in patients undergoing HD. The main routes of elimination of EGFR-TKIs are metabolism via the liver, and renal elimination is minor. The recommended doses and pharmacokinetics of these EGFR-TKIs for patients undergoing HD are similar to those for patients with normal renal function. The plasma protein binding of EGFR-TKIs is very high, and it is not necessary to adjust the dose after HD. In conclusion, EGFR-TKIs are effective and well tolerated in patients undergoing HD.

Aqueous Extract of Descuraniae Semen Attenuates Lipopolysaccharide-Induced Inflammation and Apoptosis by Regulating the Proteasomal Degradation and IRE1α-Dependent Unfolded Protein Response in A549 Cells.

Background: Lipopolysaccharide (LPS)-induced acute lung injury (ALI) induces endoplasmic reticulum stress, unfolded protein response (UPR), apoptosis, and inflammation. Inositol-requiring enzyme 1 (IRE1)-α is important for adaptive and apoptotic UPR determination during ER stress. The aqueous extract of Descuraniae Semen (AEDS) is reported to be a safe and effective herb for the treatment of pulmonary edema as it shows anti-inflammatory activities. Methods: We investigated the effects of AEDS on LPS-induced ALI in A549 cells with respect to the regulation of IRE1α-dependent UPR, proteasomal degradation, mitochondrial membrane potential (MtMP), inflammation, and apoptosis. Results: AEDS attenuated ER stress by regulating the proteasomal degradation. LPS induced ER stress [binding immunoglobulin protein (BiP), phosphorylated IRE1α, sliced X-box binding protein 1 [XBP1s], phosphorylated cJUN NH2-terminal kinase (pJNK), B-cell lymphoma (Bcl)-2-associated X (Bax), Bcl-2], inflammation (nucleus factor-kappa B (NF-κB) p65 nuclear translocation, nucleus NF-κB, pro-inflammatory cytokines] and apoptosis [C/EBP homologous protein (CHOP), cytochrome c, caspase-8, and caspase-6, and TUNEL] were significantly attenuated by AEDS treatment in A549 cells. AEDS prevents LPS-induced decreased expression of MtMP in A549 cells. Conclusions: AEDS attenuated LPS-induced inflammation and apoptosis by regulating proteasomal degradation, promoting IRE1α-dependent adaptive UPR, and inhibiting IRE1α-dependent apoptotic UPR. Moreover, IRE1α-dependent UPR plays a pivotal role in the mechanisms of LPS-induced ALI. Based on these findings, AEDS is suggested as a potential therapeutic option for treating patients with ALI.

Comparison of T790M Acquisition After Treatment With First- and Second-Generation Tyrosine-Kinase Inhibitors: A Systematic Review and Network Meta-Analysis.

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.

Deciphering the role of damage-associated molecular patterns and inflammatory responses in acute lung injury.

Acute lung injury (ALI) is characterized by diffuse pulmonary infiltrates and causes great mortality. ALI presents with overproduction of proinflammatory cytokines, cell death, destruction of alveoli-endothelial barriers, and neutrophil infiltration in lung tissues. Damage-associated molecular patterns (DAMPs) are molecules released from damaged cells due to infection, trauma, etc. DAMPs activate innate and adaptive immunity, trigger inflammatory responses, and are important in the initiation and development of ALI. We reviewed the literatures on DAMPs in ALI. Alveolar macrophages (AMs), neutrophils, and epithelial cells (AECs) are important in the pathogenesis of ALI. We comprehensively analyzed the interaction between DAMPs and AMs, alveolar neutrophils, and AECs. During the initial stage of ALI, ruptured cell membranes or destroyed mitochondria release DAMPs. DAMPs activate the inflammasome in nearby sentinel immune cells, such as AMs. AMs produce IL-1ß and other cytokines. These mediators upregulate adhesion molecules of the capillary endothelium that facilitate neutrophil recruitment. The recruited neutrophils detect DAMPs using formyl peptide receptors on the membrane, guiding their migration to the injured site. The accumulation of immune cells, cytokines, chemokines, proteases, etc., results in diffuse alveolar damage and pulmonary hyperpermeability with protein-rich fluid retention. Some clinical studies have shown that patients with ALI with higher circulating DAMPs have higher mortality rates. In conclusion, DAMPs are important in the initiation and progression of ALI. The interactions between DAMPs and AMs, neutrophils, and AECs are important in ALI. This review comprehensively addresses the mechanisms of DAMPs and their interactions in ALI.