A nationwide case-referent study on elevated risks of adenocarcinoma lung cancer by long-term PM2.5 exposure in Taiwan since 1997.

BACKGROUND: The effects of long-term PM2.5 exposures since 1968 on adenocarcinoma lung cancer (AdLC) were not studied before. METHODS: This case-referent study used nationwide cancer registry data since 1997 and air pollution data since 1968 in Taiwan to estimate risks of 30-year PM2.5 exposures on AdLC. Cases were all AdLC, while references were all non-AdLC. Individuals' 30-year PM2.5 exposures were estimated by PM2.5 levels at their residence for 30 years prior their diagnosis dates. We applied multiple logistic regression analyses to estimate PM2.5 exposures on incidence rate ratios (IRRs) between cases and references, adjusting for sex, age, smoking, cancer stage, and EGFR mutation. RESULTS: Elevation in annual ambient PM2.5 concentrations since 1968 were associated with increase in annual age-adjusted AdLC incidence since 1997. AdLC incidences were higher among females, nonsmokers, the elderly aged above 65, cases of stages IIIB to IV, and EGFR mutation. Study subjects' PM2.5 exposures averaged at 33.7 ± 7.4 µg/m3 with 162 ± 130 high PM2.5 pollution days over 30 years. Multiple logistic models showed an increase in 10 µg/m3 of PM2.5 exposures were significantly associated with 1.044 of IRR between all AdLC and all non-AdLC cases during 2011-2020. Our models also showed that females and nonsmokers and adults less than 65 years had higher IRRs than their respective counterparts. Restricted analyses showed similar effects of PM2.5 exposures on IRRs between stage 0-IIIA and IIIB-IV cases and between EGFR+ and EGFR- cases. CONCLUSIONS: Long-term exposures to PM2.5 over 30 years were associated with elevated risks of AdLC against non-AdLC, regardless of gender, age, smoking status, cancer stage, or EGFR mutation.

Risk, Predictive, and Preventive Factors for Noninfectious Ventriculitis and External Ventricular Drain Infection.

BACKGROUND: External ventricular drain (EVD) is used for monitoring intracranial pressure or diverting cerebrospinal fluid. However, confirmation of an infection is not immediate and requires obtaining culture results, often leading to the excessive use of antibiotics. This study aimed to compare noninfectious ventriculitis and EVD infection in terms of the risk factors, predictors, prognosis, and effectiveness of care bundle interventions. METHODS: This retrospective study was conducted at a medical center with 1,006 beds in northern Taiwan between January 2018 and July 2022. Standard EVD insertion protocols and care bundles have been implemented since 2018, along with the initiation of chlorhexidine. RESULTS: In total, 742 EVD cases were identified. Noninfectious ventriculitis typically presents with fever approximately 8 days following EVD placement, whereas EVD infection typically manifests as fever after 20 days. Aneurysmal subarachnoid hemorrhage was strongly associated with the development of noninfectious ventriculitis (adjusted odds ratio [OR] 2.6, 95% confidence interval [CI] 1.5-4.4). Alcoholism (adjusted OR 3.5, 95% CI 1.1-12.3) and arteriovenous malformation (adjusted OR 13.1, 95% CI 2.9-58.2) significantly increased the risk of EVD infection. The EVD infection rate significantly decreased from 3.6% (14 of 446) to 1.0% (3 of 219) (p = 0.03) after the implementation of chlorhexidine gluconate bathing. CONCLUSIONS: Aneurysmal subarachnoid hemorrhage or fever with neuroinflammation within 2 weeks of EVD placement is indicative of a higher likelihood of noninfectious ventriculitis. Conversely, patients with arteriovenous malformation, alcoholism, or fever with neuroinflammation occurring after more than 3 weeks of EVD placement are more likely to necessitate antibiotic treatment for EVD infection. Chlorhexidine gluconate bathing decreases EVD infection.

Impact of lifetime air pollution exposure patterns on the risk of chronic disease.

Long-term exposure to air pollution can lead to cardiovascular disease, metabolic syndrome, and chronic respiratory disease. However, from a lifetime perspective, the critical period of air pollution exposure in terms of health risk is unknown. This study aimed to evaluate the impact of air pollution exposure at different life stages. The study participants were recruited from community centers in Northern Taiwan between October 2018 and April 2021. Their annual averages for fine particulate matter (PM2.5) exposure were derived from a national visibility database. Lifetime PM2.5 exposures were determined using residential address information and were separated into three stages (<20, 20-40, and >40 years). We employed exponentially weighted moving averages, applying different weights to the aforementioned life stages to simulate various weighting distribution patterns. Regression models were implemented to examine associations between weighting distributions and disease risk. We applied a random forest model to compare the relative importance of the three exposure life stages. We also compared model performance by evaluating the accuracy and F1 scores (the harmonic mean of precision and recall) of late-stage (>40 years) and lifetime exposure models. Models with 89% weighting on late-stage exposure showed significant associations between PM2.5 exposure and metabolic syndrome, hypertension, diabetes, and cardiovascular disease, but not gout or osteoarthritis. Lifetime exposure models showed higher precision, accuracy, and F1 scores for metabolic syndrome, hypertension, diabetes, and cardiovascular disease, whereas late-stage models showed lower performance metrics for these outcomes. We conclude that exposure to high-level PM2.5 after 40 years of age may increase the risk of metabolic syndrome, hypertension, diabetes, and cardiovascular disease. However, models considering lifetime exposure showed higher precision, accuracy, and F1 scores and lower equal error rates than models incorporating only late-stage exposures. Future studies regarding long-term air pollution modelling are required considering lifelong exposure pattern. .1.

Therapeutic hypothermia in patients after cardiac arrest: A systematic review and meta-analysis of randomized controlled trials.

OBJECTIVE: Targeted temperature management (TTM) with therapeutic hypothermia (TH) has been used to improve neurological outcomes in patients after cardiac arrest; however, several trials have reported conflicting results regarding its effectiveness. This systematic review and meta-analysis assessed whether TH was associated with better survival and neurological outcomes after cardiac arrest. METHOD: We searched online databases for relevant studies published before May 2023. Randomized controlled trials (RCTs) comparing TH and normothermia in post-cardiac-arrest patients were selected. Neurological outcomes and all-cause mortality were assessed as the primary and secondary outcomes, respectively. A subgroup analysis according to initial electrocardiography (ECG) rhythm was performed. RESULT: Nine RCTs (4058 patients) were included. The neurological prognosis was significantly better in patients with an initial shockable rhythm after cardiac arrest (RR = 0.87, 95% confidence interval [CI] = 0.76-0.99, P = 0.04), especially in those with earlier TH initiation (<120 min) and prolonged TH duration (≥24 h). However, the mortality rate after TH was not lower than that after normothermia (RR = 0.91, 95% CI = 0.79-1.05). In patients with an initial nonshockable rhythm, TH did not provide significantly more neurological or survival benefits (RR = 0.98, 95% CI = 0.93-1.03 and RR = 1.00, 95% CI = 0.95-1.05, respectively). CONCLUSION: Current evidence with a moderate level of certainty suggests that TH has potential neurological benefits for patients with an initial shockable rhythm after cardiac arrest, especially in those with faster TH initiation and longer TH maintenance.

Association of air pollution exposure with exercise-induced oxygen desaturation in COPD.

BACKGROUND: There is a link between exposure to air pollution and the increased prevalence of chronic obstructive pulmonary disease (COPD) and declining pulmonary function, but the association with O2 desaturation during exercise in COPD patients with emphysema is unclear. Our aims were to estimate the prevalence of O2 desaturation during exercise in patients with COPD, and determine the association of exposure to air pollution with exercise-induced desaturation (EID), the degree of emphysema, and dynamic hyperinflation (DH). METHODS: We assessed the effects of 10-year prior to the HRCT assessment and 7 days prior to the six-minute walking test exposure to particulate matter with an aerodynamic diameter of < 10 µm (PM10) or of < 2.5 µM (PM2.5), nitrogen dioxide (NO2), and ozone (O3) in patients with emphysema in this retrospective cohort study. EID was defined as a nadir standard pulse oximetry (SpO2) level of < 90% or a delta (△)SpO2 level of ≥ 4%. Ambient air pollutant (PM2.5, PM10, O3, and NO2) data were obtained from Taiwan Environmental Protection Administration (EPA) air-monitoring stations, usually within 10 km to each participant's home address. RESULTS: We recruited 141 subjects with emphysema. 41.1% of patients with emphysema exhibited EID, and patients with EID had more dyspnea, worse lung function, more severe emphysema, more frequent acute exacerbations, managed a shorter walking distance, had DH, and greater long-term exposure to air pollution than those without EID. We observed that levels of 10-year concentrations of PM10, PM2.5, and NO2 were significantly associated with EID, PM10 and PM2.5 were associated with the severity of emphysema, and associated with DH in patients with emphysema. In contrast, short-term exposure did not have any effect on patients. CONCLUSION: Long-term exposure to ambient PM10, PM2.5 and NO2, but not O3, was associated with EID.

Lnc-IL7R alleviates PM2.5-mediated cellular senescence and apoptosis through EZH2 recruitment in chronic obstructive pulmonary disease.

BACKGROUND: Long-term exposure to PM2.5 (particulate matter with an aerodynamic diameter of ≤ 2.5 µm) is associated with pulmonary injury and emphysema in patients with chronic obstructive pulmonary disease (COPD). We investigated mechanisms through which the long noncoding RNA lnc-IL7R contributes to cellular damage by inducing oxidative stress in COPD patients exposed to PM2.5. METHODS: Associations of serum lnc-IL7R levels with lung function, emphysema, and previous PM2.5 exposure in COPD patients were analyzed. Reactive oxygen species and lnc-IL7R levels were measured in PM2.5-treated cells. The levels of lnc-IL7R and cellular senescence-associated genes, namely p16INK4a and p21CIP1/WAF1, were determined through lung tissue section staining. The effects of p16INK4a or p21CIP1/WAF1 regulation were examined by performing lnc-IL7R overexpression and knockdown assays. The functions of lnc-IL7R-mediated cell proliferation, cell cycle, senescence, colony formation, and apoptosis were examined in cells treated with PM2.5. Chromatin immunoprecipitation assays were conducted to investigate the epigenetic regulation of p21CIP1/WAF1. RESULTS: Lnc-IL7R levels decreased in COPD patients and were negatively correlated with emphysema or PM2.5 exposure. Lnc-IL7R levels were upregulated in normal lung epithelial cells but not in COPD cells exposed to PM2.5. Lower lnc-IL7R expression in PM2.5-treated cells induced p16INK4a and p21CIP1/WAF1 expression by increasing oxidative stress. Higher lnc-IL7R expression protected against cellular senescence and apoptosis, whereas lower lnc-IL7R expression augmented injury in PM2.5-treated cells. Lnc-IL7R and the enhancer of zeste homolog 2 (EZH2) synergistically suppressed p21CIP1/WAF1 expression through epigenetic modulation. CONCLUSION: Lnc-IL7R attenuates PM2.5-mediated p21CIP1/WAF1 expression through EZH2 recruitment, and its dysfunction may augment cellular injury in COPD.

3-Nitrobenzanthrone promotes malignant transformation in human lung epithelial cells through the epiregulin-signaling pathway.

Exposure to environmental and occupational contaminants leads to lung cancer. 3-Nitrobenzanthrone (3-nitro-7H-benz[de]anthracen-7-one, 3-NBA) is a potential carcinogen in ambient air or diesel particulate matter. Studies have revealed that short-term exposure to 3-NBA induces cell death, reactive oxygen species activation, and DNA adduct formation and damage. However, details of the mechanism by which chronic exposure to 3-NBA influences lung carcinogenesis remain largely unknown. In this study, human lung epithelial BEAS-2B cells were continuously exposed to 0-10-µM 3-NBA for 6 months. NanoString analysis was conducted to evaluate gene expression in the cells, revealing that 3-NBA-mediated transformation results in a distinct gene expression signature including carbon cancer metabolism, metastasis, and angiogenesis. Alterations in tumor-promoting genes such as EREG (epiregulin), SOX9, E-cadherin, TWIST, and IL-6 were involved in epithelial cell aggressiveness. Kaplan-Meier plotter analyses indicated that increased EREG and IL-6 expressions in early-stage lung cancer cells are correlated with poor survival. In vivo xenografts on 3-NBA-transformed cells exhibited prominent tumor formation and metastasis. EREG knockout cells exposed to 3-NBA for a short period exhibited high apoptosis and low colony formation. By contrast, overexpression of EREG in 3-NBA-transformed cells markedly activated the PI3K/AKT and MEK/ERK signaling pathways, resulting in tumorigenicity. Furthermore, elevated IL-6 and EREG expressions synergistically led to STAT3 signaling activation, resulting in clonogenic cell survival and migration. Taken together, chronic exposure of human lung epithelial cells to 3-NBA leads to malignant transformation, in which the EREG signaling pathway plays a pivotal mediating role. • Short-term exposure of lung epithelial cells to 3-NBA can lead to ROS production and cell apoptosis. • Long-term chronic exposure to 3-NBA upregulates the levels of tumor-promoting genes such as EREG and IL-6. • Increased EREG expression in 3-NBA-transformed cells markedly contributes to tumorigenesis through PI3K/AKT and MEK/ERK activation and synergistically enhances the IL-6/STAT3 signaling pathway, which promotes tumorigenicity.

Impaired lnc-IL7R modulatory mechanism of Toll-like receptors is associated with an exacerbator phenotype of chronic obstructive pulmonary disease.

Patients with chronic obstructive pulmonary disease (COPD) are susceptible to bacterial infections, which worsen lung inflammation and contribute to lung function decline and acute exacerbation. Long noncoding (lnc) RNAs are emerging regulators of inflammation with unknown clinical relevance. Herein, we report that levels of the Toll-like receptor (TLR)-related lnc interleukin (IL) 7 receptor (IL7R) were significantly reduced in peripheral blood mononuclear cells from patients with COPD compared with those from normal controls, and the levels were correlated with pulmonary function. Moreover lnc-IL7R levels were reduced in lavaged alveolar macrophages and primary human small airway epithelial cells (HSAEpCs) from patients with COPD. Lnc-IL7R knockdown in primary human macrophages, HSAEpCs, and human pulmonary microvascular endothelial cells (HPMECs) significantly augmented the induction of proinflammatory mediators after TLR2/4 activation. By contrast, lnc-IL7R overexpression attenuated inflammation after TLR2/4 activation. Similar results with lnc-IL7R-mediated inflammation were observed in COPD HSAEpCs. Mechanistically, lnc-IL7R mediated a repressive chromatin state of the proinflammatory gene promoter as a result of decreased acetylation (H3K9ac) and increased methylation (H3K9me3 and H3K27me3). Plasma lnc-IL7R levels were reduced in patients with COPD who experienced more acute exacerbation in the previous year. Notably, patients with lower lnc-IL7R levels in the subsequent year had increased exacerbation risk. Low lnc-IL7R expression in COPD may augment TLR2/4-mediated inflammation and be associated with acute exacerbation.

Combination therapies with thiazolidinediones are associated with a lower risk of acute exacerbations in new-onset COPD patients with advanced diabetic mellitus: a cohort-based case-control study.

BACKGROUND: The effects of oral antihyperglycaemic drugs (OADs) for type 2 diabetes mellitus (T2DM) on the outcomes of co-existing chronic obstructive pulmonary disease (COPD) patients are not well studied. We examined the association of combinational OADs and the risk of acute exacerbations of COPD (AECOPD) in T2DM patients with co-existing COPD. METHODS: A cohort-based case-control study was conducted using data from the National Health Insurance Research Database of Taiwan. Among new-onset COPD-T2DM patients, 65,370 were prescribed metformin and 2nd-line OADs before the date of COPD onset. Each AECOPD case was matched to 4 randomly selected controls according to the propensity score estimated by the patient's baseline characteristics. Conditional logistic regression analysis was performed to estimate the association between AECOPD risk and OAD use. RESULTS: Among COPD-T2DM patients, 3355 AECOPD cases and 13,420 matched controls were selected. Of the patients treated with a double combination of oral OADs (n = 12,916), those treated with sulfonylurea (SU) and thiazolidinediones (TZD) had a lower AECOPD risk than the patients who received metformin (MET) and SU, with an adjusted odds ratio (OR) of 0.69 (95% confidence interval [CI] 0.51-0.94, P = 0.02). Of the patients with a triple combination of oral OADs (n = 3859), we found that those treated with MET, SU and TZD had a lower risk of AECOPD (adjusted OR 0.81 (0.68-0.96, P = 0.01) than a combination of MET, SU and α-glucosidase inhibitors (AGIs) regardless of the level of COPD complexity. CONCLUSION: Combination therapies with TZD were associated with a reduced risk of AECOPD in advanced T2DM patients with co-existing COPD.

Suppressor of variegation 3-9 homologue 1 impairment and neutrophil-skewed systemic inflammation are associated with comorbidities in COPD.

BACKGROUND: Systemic manifestations and comorbidities are characteristics of chronic obstructive pulmonary disease (COPD) and are probably due to systemic inflammation. The histone methyltransferase SUV39H1 controls the Th1/Th2 balance. We previously reported that reduced SUV39H1 expression contributed to abnormal inflammation in COPD. Here, we aimed to determine whether impaired SUV39H1 expression in COPD patients associated with neutrophilic/eosinophilic inflammation responses and comorbidities. METHODS: A total of 213 COPD patients and 13 healthy controls were recruited from the Shuang Ho Hospital, Taipei Medical University. SUV39H1 levels in peripheral blood mononuclear cells (PBMCs) from 13 healthy and 30 COPD participants were measured by immunoblotting. We classified the patients into two groups based on low (fold change, FC < 0.5) and high SUV39H1 expression (FC ≥ 0.5) compared to normal controls. Clinical outcomes including neutrophil or eosinophil counts associated with SUV39H1-related inflammation were evaluated by Chi square analyses or Mann-Whitney U test. The correlations between the percentage of neutrophils and number of COPD comorbidities or Charlson Comorbidity Index (CCI) scores were performed by Spearman's rank analysis. RESULTS: Low SUV39H1 expression group had high neutrophil counts relative to high SUV39H1expression group. In the COPD cohort, the high comorbidity group (≥ 2 comorbidities) had higher counts of whole white blood cell (WBC) and neutrophil, and lower proportion of eosinophil and eosinophil/neutrophil, as compared with low comorbidity group (0 and 1 comorbidities). The quantity of neutrophils was associated with COPD comorbidities (Spearman's r = 0.388, p < 0.001), but not with CCI scores. We also found that the high comorbidity group had more exacerbations per year compared with low comorbidity group (1.5 vs. 0.9 average exacerbations, p = 0.005). However, there were no significant differences between groups with these non-frequent (0-1 exacerbation) and frequent exacerbations per year (> 1 exacerbation) in numbers of WBC and proportion of neutrophils, eosinophils or eosinophil/neutrophil. Finally, patients with high comorbidities had lower SUV39H1 levels in their PBMCs than did those with low comorbidities. CONCLUSION: Blood neutrophil counts are associated with comorbidities in COPD patients. Impaired SUV39H1 expression in PBMCs from COPD patients are correlated with neutrophilic inflammation and comorbidities.

Impact of tumor disappearance ratio on the prognosis of lung adenocarcinoma ≤2 cm in size: A retrospective cohort study.

BACKGROUND/PURPOSE: Lung cancer patients can have advanced-stages at diagnosis, even the tumor size is ≤2 cm. We aimed to study the relationship between image characteristics, clinical, and patholoigcal results. METHODS: We retrospectively enrolled patients with lung adenocarcinoma at Taichung Veterans General Hospital and Chang Gung Memorial Hospital from 2007 to 2015, who were diagnosed with treatment naïve primary tumor lesions at sizes less than 2 cm, as measured by computed tomography (CT) scans. The patient was analyzed for lymph node (LN) and distant metastasis evaluation, with clinicopathological characteristics, including tumor-disappearance ratio (TDR) (tumor diameter at the mediastinal/lung window) over chest CT scans, pathological diagnosis, disease-free survival (DFS), and overall survival (OS). RESULTS: Totally 280 patients were surveyed initially and showed significantly increase of clinical LN involvement and distant metastasis when TDR ≤75% compared with >75% (21.6% vs 0% for LN involvement; 27.1% vs 0% for distant metastasis; both p < 0.001). We included 199 patients having surgical treatment and follow-up for the survival analysis. With a TDR ≤75%, significantly worse DFS (HR, 19.23; 95% CI, 2.60-142.01; p = 0.004) and a trend of worse OS (HR, 4.97; 95% CI, 0.61-40.61; p = 0.134) were noted by Kaplan-Meier method. TDR ≤75% revealed more advanced pathological stage, and more tumors containing micropapillary or solid subtypes when diagnosed adenocarcinoma. CONCLUSION: For lung cancer patients with primary tumor ≤2 cm, TDR ≤75% was related to more advanced stages, the presence of micropapillary or solid components of adenocarcinoma subtypes, worse DFS, and a trend of worse OS.

Resuscitation fluid types in sepsis, surgical, and trauma patients: a systematic review and sequential network meta-analyses.

BACKGROUND: Crystalloids and different component colloids, used for volume resuscitation, are sometimes associated with various adverse effects. Clinical trial findings for such fluid types in different patients' conditions are conflicting. Whether the mortality benefit of balanced crystalloid than saline can be inferred from sepsis to other patient group is uncertain, and adverse effect profile is not comprehensive. This study aims to compare the survival benefits and adverse effects of seven fluid types with network meta-analysis in sepsis, surgical, trauma, and traumatic brain injury patients. METHODS: Searched databases (PubMed, EMBASE, and Cochrane CENTRAL) and reference lists of relevant articles occurred from inception until January 2020. Studies on critically ill adults requiring fluid resuscitation were included. Intervention studies reported on balanced crystalloid, saline, iso-oncotic albumin, hyperoncotic albumin, low molecular weight hydroxyethyl starch (L-HES), high molecular weight HES, and gelatin. Network meta-analyses were conducted using random-effects model to calculate odds ratio (OR) and mean difference. Risk of Bias tool 2.0 was used to assess bias. Confidence in Network Meta-Analysis (CINeMA) web application was used to rate confidence in synthetic evidence. RESULTS: Fifty-eight trials (n = 26,351 patients) were identified. Seven fluid types were evaluated. Among patients with sepsis and surgery, balanced crystalloids and albumin achieved better survival, fewer acute kidney injury, and smaller blood transfusion volumes than saline and L-HES. In those with sepsis, balanced crystalloids significantly reduced mortality more than saline (OR 0.84; 95% CI 0.74-0.95) and L-HES (OR 0.81; 95% CI 0.69-0.95) and reduced acute kidney injury more than L-HES (OR 0.80; 95% CI 0.65-0.99). However, they required the greatest resuscitation volume among all fluid types, especially in trauma patients. In patients with traumatic brain injury, saline and L-HES achieved lower mortality than albumin and balanced crystalloids; especially saline was significantly superior to iso-oncotic albumin (OR 0.55; 95% CI 0.35-0.87). CONCLUSIONS: Our network meta-analysis found that balanced crystalloids and albumin decreased mortality more than L-HES and saline in sepsis patients; however, saline or L-HES was better than iso-oncotic albumin or balanced crystalloids in traumatic brain injury patients. TRIAL REGISTRATION: PROSPERO website, registration number: CRD42018115641).

Antiplatelet agents and anticoagulants increased the bleeding risk of bedside percutaneous dilational tracheostomy in critically ill patients.

BACKGROUND: The main objective of this study was to investigate the safety of bedside percutaneous dilational tracheostomy (PDT) by pulmonologists in critically ill patients, and the factors associated with complications resulting from PDT. METHODS: We retrospectively enrolled critically ill patients who had undergone bedside PDT in the intensive care units (ICUs) and respiratory care center from February 2016 to December 2018. RESULTS: A total of 312 patients were included for analysis, with a mean age of 69.6 ± 17.7 years. Two hundred and eight of the patients were male (66.7%). The mean acute physiology and chronic health evaluation II score was 25.3 ± 6.3, and the mean body mass index was 22.4 ± 4.2. Most of the patients were intubated due to respiratory disorders (51.3%). Fifty-six patients (17.9%) received antiplatelet agents or an anticoagulant regularly prior to PDT. All enrolled patients were undergone bedside PDT successfully. The total complication rate of PDT was 14.4%. Patients who took antiplatelet agents or anticoagulants regularly before PDT had a higher risk of bleeding than patients who went without (26.8% versus 7.0%, adjusted odds ratio 4.93 [95% f 2.16-11.25], p < 0.001). Finally, a longer length of intubation resulted in a higher probability in the length of ICU stay being ≧28 days (adjusted odds ratio 1.11 [95% CI 1.08-1.14], p < 0.001). CONCLUSION: Our study demonstrated that it was feasible for pulmonologists to perform bedside PDT in critically ill patients. However, antiplatelet agents and anticoagulants use increased the risk of bleeding in PDT patients.

First tidal volume greater than 8 mL/kg is associated with increased mortality in complicated influenza infection with acute respiratory distress syndrome.

BACKGROUNDS: Severe influenza infection causes substantial morbidity and mortality worldwide and remains an important threat to global health. This study addressed factors related to treatment outcomes in subjects of complicated influenza infection with acute respiratory distress syndrome (ARDS) during the Taiwan epidemic in the Spring of 2016. METHODS: This is a retrospective study conducted by Taiwan Severe Influenza Research Consortium (TSIRC), including eight tertiary referral medical centers. Patients with virology-proven influenza infection admitted to intensive care unit (ICU) between January and March 2016 were included for analysis. RESULTS: We identified 263 patients with complicated influenza infection who fulfilled ARDS criteria; the mean age was 59.8 ± 14.6 (years), and 66.1% (166/263) were male. Type A influenza (77.9%, 205/263) virus was the main pathogen during this epidemic. The 30-day mortality rate was 23.2% (61/263). The mean tidal volume (VT) in the first three days after intubation was greater than 8 mL/kg of predicted body weight (PBW). Patients whose first measured VT was >8 mL/kg PBW had an increased 30-day mortality (p = 0.04, log-rank test). In a multivariate Cox proportional hazard regression model, an increase of 1 mL/kg PBW of first VT was associated with 26.1% increase in 30-day mortality (adjusted hazard ratio 1.261, 95% confidence interval [CI] 1.072-1.484, p < 0.01). CONCLUSION: First tidal volume, shortly after intubation, greater than 8 mL/kg PBW is an independent risk factor for mortality in complicated influenza infection with ARDS. Timely recognition of ARDS with strict adherence to protective ventilation strategy of lowering VT may be important in reducing mortality.

[Improving the Accuracy Rate of Analgesics and Sedatives Administration in an Intensive Care Unit].

BACKGROUND: Patients with respiratory failure needing mechanical ventilation are common in the intensive care unit. These patients often require sedative and analgesic agents to alleviate their discomfort and to avoid causing associated safety issues. However, prolonged post-awakening confusion and changes in perception after withdrawal from sedatives and analgesic agents are common in daily practice. Thus, the optimal use of sedative and analgesic agents remains an important issue in the intensive care unit. PURPOSE: To optimize sedation by raising the rate of accuracy for administering analgesic and sedative agents in the intensive care unit from 30.44% to 60.88%. METHODS: We first analyzed the problem from the current situation of the daily practice and revised the protocol of using analgesic and sedative agents. In order to achieve an optimal outcome, the authors further arranged staff education and bedside training and established an audit system to check and improve protocol adherence. RESULTS: The rate of accuracy for administering sedatives and analgesics improved from 34% to 93%. CONCLUSIONS: With appropriately scaled protocols of sedatives and analgesics administration, intensive care nurses may easily target the consistent and optimal assessment and provide pain relief prior to sedation, which will improve the quality of sedation and patient safety.

EGFR mutation and lobar location of lung adenocarcinoma.

The objective of this study was to investigate the associations among lung cancer location, and epidermal growth factor receptor (EGFR) mutation status. Treatment-naive, pathologically confirmed lung adenocarcinomas with tumor specimens available for genetic analysis were included from 2011 through 2014. Overall, 1771 patients with lung adenocarcinoma were included for analysis, after excluding those with carcinoma not otherwise specified, or synchronous multiple primary lung cancers. The median age was 64 years, and the female:male and never smoker:ever smoker ratios were 930:855 (52:48%) and 1167:604 (65:35%), respectively. The EGFR mutation rate was 56%. Among patients, 1093 (62%) had primary tumors in the upper lobes. Compared with the characteristics of the EGFR wild-type, tumors with EGFR activating mutations were more common in women (P < 0.001), never smokers (P < 0.001), and in the upper lobes (P = 0.004). Among EGFR activating mutations, compared with the EGFR exon 19 deletion, L858R mutation were more common in women (P = 0.002), never smokers (P = 0.038), and the upper lobes P < 0.0005). The present study is the first to address that different pulmonary lobar locations might harbor different EGFR mutation subtypes. We demonstrated that adenocarcinomas with L858R mutation, rather than exon 19 deletion or wild-type EGFR gene, prefer to locate over the upper lungs. This phenomenon was more significant in females and never-smokers, implying the result of complex interactions between genetic susceptibility and environmental factors. Therefore, EGFR L858R mutation and exon 19 deletion may not be identical disease entity from the point of carcinogenesis.

[The effectiveness of care bundles in maintaining the skin integrity and reducing the incidence density of pressure ulcers in lung cancer inpatients].

BACKGROUND & PROBLEMS: Pressure ulcers are tissue defects that form on the skin as a result of progressive skin damage. Pressure ulcers are a skin-integrity-related care issue and an important clinical indicator of care quality, especially for lung cancer inpatients who face rapidly deteriorating health conditions due to multiple symptoms and the side effects of treatment. Treating severe pressure ulcers may consume considerable manpower, time, and medical resources. Pressure ulcers may be avoided or effectively treated when nurses conduct proper skin assessments and care for wounds properly. PURPOSE: This project evaluates the efficacy of skin care bundles in terms of reducing the incidence density of pressure ulcers in lung cancer inpatients. RESOLUTION: Data gathered between January 2010 and March 2011 showed unstable incidence density for pressure ulcers. The average pressure-ulcer incidence density in lung cancer inpatients was 2.09%, which was 8-times higher than the average for all patients. Using evidence-based care bundles for pressure ulcer prevention, we trained nurse staffs to incorporate these bundles into their clinical daily care of lung cancer patients in our hospital. RESULTS: During the study period between November 2011 and January 2012, the pressure-ulcer incidence density gradually fell to 0.55%. The incidence density continued to fall to 0.33% over the subsequent 8 months. CONCLUSIONS: We used the concept of "care bundles" to establish a standard skin-care protocol for advanced lung cancer inpatients. This protocol improved the clinical ability of nursing staffs and effectively maintained skin care quality in lung cancer patients.

Combining wireless radar sleep monitoring device with deep machine learning techniques to assess obstructive sleep apnea severity.

STUDY OBJECTIVES: The gold standard for diagnosing obstructive sleep apnea (OSA) is polysomnography (PSG). However, PSG is a time-consuming method with clinical limitations. This study aimed to create a wireless radar framework to screen the likelihood of two levels of OSA severity (i.e., moderate-to-severe and severe OSA) in accordance with clinical practice standards. METHODS: We conducted a prospective, simultaneous study using the wireless radar system and PSG in a Northern Taiwan sleep center, involving 196 patients. The wireless radar sleep monitor, incorporating hybrid models such as deep neural decision trees, estimated the respiratory disturbance index relative to the total sleep time established by PSG (RDIPSG_TST), by analyzing continuous-wave signals indicative of breathing patterns. Analyses were performed to examine the correlation and agreement between the RDIPSG_TST and apnea-hypopnea index (AHI), results obtained through PSG. Cut-off thresholds for RDIPSG_TST were determined using Youden's index, and multiclass classification was performed, after which the results were compared. RESULTS: A strong correlation (ρ = 0.91) and agreement (average difference of 0.59 events/h) between AHI and RDIPSG_TST were identified. In terms of the agreement between the two devices, the average difference between PSG-based AHI and radar-based RDIPSG_TST was 0.59 events/h, while 187 out of 196 cases (95.41%) fell within the 95% confidence interval of differences. A moderate-to-severe OSA model achieved an accuracy of 90.3% (cut-off threshold for RDIPSG_TST: 19.2 events/h). A severe OSA model achieved an accuracy of 92.4% (cut-off threshold for RDIPSG_TST: 28.86 events/h). The mean accuracy of multiclass classification performance using these cut-off thresholds was 83.7%. CONCLUSIONS: The wireless-radar-based sleep monitoring device, with cut-off thresholds, can provide rapid OSA screening with acceptable accuracy, and also alleviate the burden on PSG capacity. However, to independently apply this framework, the function of determining the radar-based total sleep time requires further optimizations and verification in future work.

Prediction value of neutrophil and eosinophil count at risk of COPD exacerbation.

INTRODUCTION: Predicting acute exacerbations (AEs) in chronic obstructive pulmonary disease (COPD) is crucial. This study aimed to identify blood biomarkers for predicting COPD exacerbations by inflammatory phenotypes. MATERIALS AND METHODS: We analyzed blood cell counts and clinical outcomes in 340 COPD patients aged 20-90 years. Patients were categorized into eosinophilic inflammation (EOCOPD) and non-eosinophilic inflammation (N-EOCOPD) groups. Blood cell counts, eosinophil-to-lymphocyte ratio (ELR), neutrophil-to-lymphocyte ratio (NLR) and neutrophil-to-eosinophil ratio (NER) were calculated. Linear and logistic regression models assessed relationships between health outcomes and blood cell counts. RESULTS: EOCOPD patients had distinct characteristics compared to N-EOCOPD patients. Increased neutrophil % and decreased lymphocyte % were associated with reduced pulmonary function, worse quality of life and more exacerbations, but they did not show statistical significance after adjusting by age, sex, BMI, smoking status, FEV1% and patient's medication. Subgroup analysis revealed a 1.372-fold increase in the OR of AE for every 1 unit increase in NLR in EOCOPD patients (p < .05). In N-EOCOPD patients, every 1% increase in blood eosinophil decreased the risk of exacerbation by 59.6%. CONCLUSIONS: Our study indicates that distinct white blood cell profiles in COPD patients, with or without eosinophilic inflammation, can help assess the risk of AE in clinical settings.

Associations between air pollution, intracellular-to-extracellular water distribution, and obstructive sleep apnea manifestations.

Background: Exposure to air pollution may be a risk factor for obstructive sleep apnea (OSA) because air pollution may alter body water distribution and aggravate OSA manifestations. Objectives: This study aimed to investigate the mediating effects of air pollution on the exacerbation of OSA severity through body water distribution. Methods: This retrospective study analyzed body composition and polysomnographic data collected from a sleep center in Northern Taiwan. Air pollution exposure was estimated using an adjusted nearest method, registered residential addresses, and data from the databases of government air quality motioning stations. Next, regression models were employed to determine the associations between estimated air pollution exposure levels (exposure for 1, 3, 6, and 12 months), OSA manifestations (sleep-disordered breathing indices and respiratory event duration), and body fluid parameters (total body water and body water distribution). The association between air pollution and OSA risk was determined. Results: Significant associations between OSA manifestations and short-term (1 month) exposure to PM2.5 and PM10 were identified. Similarly, significant associations were identified among total body water and body water distribution (intracellular-to-extracellular body water distribution), short-term (1 month) exposure to PM2.5 and PM10, and medium-term (3 months) exposure to PM10. Body water distribution might be a mediator that aggravates OSA manifestations, and short-term exposure to PM2.5 and PM10 may be a risk factor for OSA. Conclusion: Because exposure to PM2.5 and PM10 may be a risk factor for OSA that exacerbates OSA manifestations and exposure to particulate pollutants may affect OSA manifestations or alter body water distribution to affect OSA manifestations, mitigating exposure to particulate pollutants may improve OSA manifestations and reduce the risk of OSA. Furthermore, this study elucidated the potential mechanisms underlying the relationship between air pollution, body fluid parameters, and OSA severity.