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Yi-Han Hsiao,1– 3 Ching-Min Tseng,2,4 Chau-Chyun Sheu,5,6 Hsin-Yi Wang,7,8 Hsin-Kuo Ko,2,9 Kang-Cheng Su,2,10 Chi-Wei Tao,4 Ming-Ju Tsai,5,6,* Yen-Fu Chen7,8,* 1Division of General Chest Medicine, Department of Chest Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; 2School of Medicine, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan; 3Department and Institute of Physiology, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan; 4Division of Chest Medicine, Department of Internal Medicine, Cheng-Hsin General Hospital, Taipei, Taiwan; 5Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan; 6Department of Internal Medicine, School of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; 7Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, National Taiwan University Hospital Yunlin Branch, Yunlin, Taiwan; 8Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan; 9Division of Respiratory Therapy, Department of Chest Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; 10Division of Clinical Respiratory Physiology, Department of Chest Medicine, Taipei Veterans General Hospital, Taipei, Taiwan*These authors contributed equally to this workCorrespondence: Ming-Ju Tsai, Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Kaohsiung Medical University Hospital, No. 100, Tz-You 1st Road, 807, Kaohsiung, Taiwan, Tel +886 7 3121101, Ext. 5651, Fax +886 7 3161210, Email SiegfriedTsai@gmail.com Yen-Fu Chen, Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, National Taiwan University Hospital Yunlin Branch, Yunlin, Taiwan, Tel +886 5 5323911, Ext. 2501, Email yenfu1228@gmail.comPurpose: Inadequate inhaler technique and nonadherence to therapy are associated with poorer clinical outcomes in chronic obstructive pulmonary disease (COPD). Shared decision-making (SDM), based on clinical evidence, patient goals and preferences, improves quality of care. This study aims to investigate the initial patients’ choices of inhaler devices in patients with newly-diagnosed COPD after an SDM process.Patients and Methods: We conducted a prospective, observational, multi-center study in four hospitals in Taiwan from December 2019 to July 2021. All treatment-naïve patients with newly-diagnosed COPD who were able to use three different inhalers of dual bronchodilators (Respimat®, Ellipta®, and Breezhaler®) in the outpatient setting were enrolled. After an SDM process, every patient was prescribed with one inhaler chosen by him- or herself. Errors of using inhalers were recorded after prescription of the inhaler, and at the follow-up visit a month later. The patients’ adherence, satisfaction score, and willingness to keep the initially chosen inhaler were investigated.Results: In 109 enrolled patients, 43, 45, and 21 patients chose Respimat®, Ellipta®, and Breezhaler®, respectively. Patients chose different inhalers had similar rates of critical error on both visits, while the rates greatly decrease on the follow-up visit, no matter which inhaler devices they chose initially. The majority of patients had good adherence (use as the prescription daily, n = 79, 82%), satisfaction (satisfaction score ≥ 4, n = 70, 73%), and strong willingness to keep the initial inhaler (n = 89, 93%) on the follow-up visit regardless of disease severity and their comorbidities.Conclusion: SDM might facilitate inhaler choosing, reduce inhaler errors (versus baseline) with good adherence, satisfaction and strong willingness to keep the initial inhaler in patients with newly-diagnosed COPD.Keywords: shared decision-making, inhaler choice, dual bronchodilators, chronic obstructive pulmonary disease

The purpose of this study was to evaluate the long-term outcomes of endovascular treatment of central venous stenosis in patients with arteriovenous fistulas (AVFs) for hemodialysis. Five hundred sixty-three patients with AVFs who were referred for a fistulogram were enrolled in this study. Among them, 44 patients showed stenosis (n = 35) or occlusions (n = 9) in the central vein. For the initial treatment, 26 patients underwent percutaneous transluminal angioplasty (PTA) and 15 patients underwent stent placements. Periods between AVF formation and first intervention ranged from 3 to 144 months. Each patient was followed for 14 to 60 months. Procedures were successful in 41 of 44 patients (93.2%). Primary patency rates for PTA at 12 and 36 months were 52.1% and 20.0%, and assisted primary patency rates were 77.8% and 33.3%, respectively. Primary patency rates for stent at 12 and 36 months were 46.7% and 6.7%, and assisted primary patency rates were 60.0% and 20.0%, respectively. Fifteen of 26 patients with PTAs underwent repeated interventions because of restenosis. Fourteen of 15 patients with a stent underwent repeated interventions because of restenosis and combined migration (n = 1) and shortening (n = 6) of the first stent. There was no significant difference in patency between PTAs and stent placement (p > 0.05). Average AVF patency duration was 61.8 months and average number of endovascular treatments was 2.12. In conclusion, endovascular treatments of central venous stenosis could lengthen the available period of AVFs. There was no significant difference in patency between PTAs and stent placement. [ABSTRACT FROM AUTHOR]

Background: Among treatment modalities for unresectable hepatocellular carcinoma (HCC), radiofrequency ablation (RFA) is getting popular due to low morbidity and its effectiveness. However, when the tumor is located just under the diaphragm, a percutaneous approach for RFA is often impossible because of the difficulty in visualizing the tumor with conventional ultrasonographic examination.Method: Simultaneous thoraco-laparoscopic transthoracic transdiaphragmatic intraoperative RFA was performed on a 55 year-old male with HCC just beneath the diaphragm as well as laparoscopic RFA for dysplastic nodule near the gallbladder. Most of all, the patient wanted to undergo liver transplantation for the HCC and underlying liver cirrhosis. Therefore we chose to provide this procedure as a bridge to the liver transplantation. A total of four trocars (12 mm, 10 mm, 5 mm trocars for laparoscopy, and one 5 mm trocar for thoracoscopy), a 10 mm flexible laparoscope, a 5 mm thoracoscpe, and a laparoscopic ultrasound were used for this surgical procedure. After finishing laparoscopic RFA for dysplastic nodule near the gallbladder, the patient was placed into the left lateral decubitus for dual-scope guided transthoracic transdiaphragmatic intraoperative RFA. Complete separation of the diaphragm from the hepatic dome and good visualization of the subdiaphragmatic vessels provided a safe procedure without any injury to the diaphragm and other vessels.Results: The operative time was 240 minutes and the blood loss was zero. The postoperative course was uneventful. The diet was started on the operative day. A chest tube and an abdominal drain was removed on first day after surgery. The patient discharged on the second day after surgery. The patient has been followed up for three months after the dual-scope guided intraoperative RFA without any evidence of tumor recurrence. He is now actively being evaluated for liver transplantation.Conclusion: Dual-scope guided (simultaneous thoraco-laparoscopic) transthoracic transdiaphragmatic intraoperative RFA is an easy, safe, and effective minimal invasive modality for treatment of the selective patient with HCC, with liver cirrhosis, which is located immediately under the diaphragm. Further experiences and a long term follow up is mandatory. [ABSTRACT FROM AUTHOR]

Objectives: To compare the efficacy of transarterial chemoembolization (TACE) and radiofrequency ablation (RFA) for patients with single small (≤ 3 cm) hepatocellular carcinoma (HCC) and preserved liver function (Child-Pugh class A)., Materials and Methods: The clinical features of treatment-naïve patients who underwent TACE and RFA as first-line treatment were balanced through propensity score matching (PSM). The primary endpoint was overall survival (OS), and the secondary endpoints were local tumor recurrence (LTR) and recurrence-free survival (RFS)., Results: The analysis included 440 patients who received TACE, and 430 patients who received RFA. After PSM adjustment (323 pairs), the 5- and 10-year OS rates were 81% and 61%, respectively, in patients who underwent RFA, and 77% and 51%, respectively, for patients who underwent TACE (p = 0.021). Subgroup analyses showed that OS, LTR, and RFS were homogeneously better in the RFA group., Conclusion: RFA was associated with better survival outcomes than TACE in patients with single small HCC and preserved liver function., Clinical Relevance Statement: This large-scale comparative study provides evidence that radiofrequency ablation has a better overall survival rate than chemoembolization for small (≤ 3 cm) hepatocellular carcinomas., Key Points: • The relative effectiveness of transarterial chemoembolization (TACE) and radiofrequency ablation (RFA) for early HCC is unclear. • Overall survival rate was significantly higher in the RFA group. • The effects of RFA on overall survival, local tumor recurrence, and recurrence-free survival were homogeneously better in all subgroups., (© 2024. The Author(s), under exclusive licence to European Society of Radiology.)

Background and Objective: Correlations between the image analysis of CT scan, lung function and quality of life in patients with idiopathic pulmonary fibrosis (IPF) remain unclear. This study aimed to investigate the impacts of pulmonary blood-vessel distribution and the extent of fibrosis on the lung function and quality of life of patients with IPF., Methods: Patients were enrolled in an IPF registry and had completed pulmonary function tests, chest HRCT, St. George Respiratory Questionnaire (SGRQ) and echocardiography. Pulmonary blood-vessel distribution, specific image-derived airway volume (siVaw) and fibrosis extent (siVfib) were quantitatively calculated by functional respiratory imaging on HRCT., Results: The study subjects were categorized into DLco <40% pred. (n = 40) and DLco ≥40% pred. (n = 19) groups. Patients with DLco <40% pred. had significantly higher scores of SGRQ, composite physiologic index (CPI), exercise oxygen desaturation (∆SpO 2 ), siVaw, lower FVC% pred. and 6-minute walking distance% pred. The proportion of small blood vessels in the upper lobes (BV5PR-UL) was significantly correlated with CPI, DLco % Pred., FVC% pred., SGRQ and ∆SpO 2 . Only BV5PR-UL had a significant impact on all indices but not BV5PR in the lower lobes (BV5PR-LL). siVfib was significantly negatively correlated with BV5PR-UL, DLco% pred. and FVC% pred., as well as positively correlated with CPI, ∆SpO 2 and siVaw., Conclusion: BV5PR-UL and siVfib had significant correlations with lung function and may become important indicators to assess the severity of IPF and the impact on quality of life., (© 2024 The Author(s). Respirology published by John Wiley & Sons Australia, Ltd on behalf of Asian Pacific Society of Respirology.)

Background: and Purpose: With mindfulness being increasingly recognized for its potential to address psychological challenges related to advanced or terminal illnesses, palliative care professionals are incorporating mindfulness-based interventions into their practice. However, there is limited understanding of the practical applications of mindfulness in clinical settings, particularly for end-of-life patients. This study explored palliative care professionals' experiences in delivering mindfulness-based therapy to end-of-life patients, thereby aiming to inform the development of effective interventions., Materials and Methods: Semi-structured interviews were conducted with 15 palliative care professionals. Participants were asked to describe their memorable experiences in applying mindfulness in a clinical setting. Data were analyzed following Moustakas's transcendental phenomenology approach., Results: The interviews produced three themes: clinicians' mindfulness experiences form the cornerstone of their clinical application of mindfulness; creating an optimal healing environment is essential for mindfulness practice; and patient-centric mindfulness guidance should be implemented., Conclusion: This study underscores the critical role of mindfulness in end-of-life care, highlighting its integration into daily life by palliative care professionals. By drawing upon their own mindfulness experiences, palliative care professionals facilitated a therapeutic environment tailored to the unique needs of end-of-life patients. This patient-centered approach not only enhanced the quality of care but also fostered a healing connection rooted in compassion and empathy. The findings advocate for further education and development of mindfulness-based interventions, including group therapies, to support the holistic well-being of patients in collectivist cultures. Future research should further explore the practical applications and benefits of mindfulness in end-of-life care settings., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

The illness experiences of advanced cancer patients are discussed in a Taiwanese cultural context, using an interpretive ethnographic approach (interviews and participant observations) emphasizing holism and symbolic interactionism. A total of 23 advanced cancer patients from different counties in Taiwan were recruited over a 42-month period. The researcher followed their progress as they approached death to better understand their terminal cancer experiences. An interpretive analysis guided by Agar's hermeneutic cycle approach revealed five emic dimensions: feeling the oppression of death, fighting alongside family, intensifying bodily healing efforts, settling unfinished business, and ending the struggle to control pain. Implications for caregivers are discussed., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Purpose: To evaluate the safety and long-term clinical outcomes of stent-graft placement to treat hepatic arterial hemorrhage after pancreaticobiliary surgery., Materials and Methods: Outcomes were retrospectively evaluated in 61 patients (50 men and 11 women; mean age, 63 years) who underwent stent-graft placement for delayed arterial hemorrhage (after 24 hours) after pancreaticobiliary surgery from 2006 to 2023. Bleeding sites included the gastroduodenal artery stump (n = 54), common or proper hepatic artery (n = 5), and right hepatic artery (n = 2). The stent-grafts used were Viabahn (n = 27), Comvi (n = 11), Jostent (n = 3), Covera (n = 11), and Lifestream (n = 7). Technical and clinical success and adverse events (AE) were evaluated. After stent-graft placement, overall survival (OS), hemorrhage-free survival (HFS), and stent patency were evaluated., Results: The technical and clinical success rates of stent-graft placement were 97% and 93%, respectively. The severe AE rate was 12% and was significantly higher in patients who underwent pylorus-sacrificing rather than pylorus-preserving surgery (P = .001). None of the severe AEs were associated with patient mortality. Median OS after stent-graft placement was 854 days, and median HFS was 822 days. The 1-, 3-, 5-, and 10-year stent patency rates were 87%, 84%, 79%, and 72%, respectively., Conclusions: Stent-graft placement was safe and provided long-term control of hepatic arterial hemorrhage after pancreaticobiliary surgery., (Copyright © 2024 SIR. Published by Elsevier Inc. All rights reserved.)

Background: The available data on anticoagulation therapy in real-world primary care settings for atrial fibrillation (AF) patients at high risk of stroke is limited., Objective: To evaluate anticoagulation therapy and elucidate the factors associated with the selection between direct oral anticoagulants (DOACs) and warfarin., Design and Participants: This is a retrospective cohort study that included patients ≥ 18 years old at a large primary care outpatient group, a network of twenty clinics in the northeast United States between January 4, 2021 - January 4, 2023., Main Measures: Oral anticoagulation therapy in AF patients with high risk of stroke (CHA 2 DS 2 -VASc score of ≥ 2 in men or ≥ 3 in women)., Key Results: Among the 3,118 adult patients with AF and high risk of stroke (median age 77.90, IQR 71.66-84.50 years; male 57.6%), we found that older age (aOR 1.40, p = 0.003), greater BMI (25-29.9: aOR 1.32, p = 0.048; ≥ 30 aOR 1.42, p = 0.010), and taking more than five medications (aOR 2.28, p < 0.001) were more likely to be on an oral anticoagulant. Among those taking an OAC, having Medicare as the sole coverage (aOR 0.53, p = 0.032), male gender (aOR 0.69, p = 0.011), worse renal function (aOR 0.80, p = 0.021), and higher CHA 2 DS 2 -VASc score (aOR 0.88, p = 0.024) are more likely to be on warfarin than a DOAC. Patients taking more than five medications daily (6-10 medications: aOR 1.92, p = 0.013; ≥ 16: aOR = 2.10, p = 0.006) were more likely to be on an anticoagulant and may receive a DOAC over warfarin., Conclusions: AF with high stroke risk adult patients are more likely to be on an oral anticoagulant if they are older, having BMI ≥ 25, or taking more than five medications. Medicare as the sole coverage, male gender, worse renal function, and higher CHA 2 DS 2 -VASc scores are factors associated with greater warfarin usage, while patients taking over five daily medications are more likely to be prescribed DOACs., (© 2024. The Author(s), under exclusive licence to Society of General Internal Medicine.)

Introduction: The English PUMA questionnaire emerges as an effective COPD case-finding tool. We aimed to use the PUMA questionnaire in combination with peak expiratory flow rate (PEFR) to improve case-finding efficacy in Chinese population., Methods: This cross-sectional, observational study included two stages: translating English to Chinese PUMA (C-PUMA) questionnaire with linguistic validation and psychometric evaluation, followed by clinical validation. Eligible participants (with age ≥40 years, respiratory symptoms, smoking history ≥10 pack-years) were enrolled and subjected to three questionnaires (C-PUMA, COPD assessment test [CAT], and generic health survey [SF-12V2]), PEFR measurement, and confirmatory spirometry. The C-PUMA score and PEFR were incorporated into a PUMA-PEFR prediction model applying binary logistic regression coefficients to estimate the probability of COPD (P COPD )., Results: C-PUMA was finalized through standard forward-backward translation processes and confirmation of good readability, comprehensibility, and reliability. In clinical validation, 240 participants completed the study. 78/240 (32.5%) were diagnosed with COPD. C-PUMA exhibited significant validity (correlated with CAT or physical component scores of SF-12V2, both P<0.05, respectively). PUMA-PEFR model had higher diagnostic accuracy than C-PUMA alone (area under ROC curve, 0.893 vs. 0.749, P<0.05). The best cutoff values of C-PUMA and PUMA-PEFR model (P COPD ) were ≥6 and ≥0.39, accounting for a sensitivity/specificity/numbers needed to screen of 77%/64%/3 and 79%/88%/2, respectively. C-PUMA ≥5 detected more underdiagnosed patients, up to 11.5% (vs. C-PUMA ≥6)., Conclusion: C-PUMA is well-validated. The PUMA-PEFR model provides more accurate and cost-effective case-finding efficacy than C-PUMA alone in at-risk, undiagnosed COPD patients. These tools can be useful to detect COPD early., (Copyright © 2024 The Author(s). Published by Elsevier España, S.L.U. All rights reserved.)

Leukocyte cell-derived chemotaxin 2 (LECT2) is a protein initially isolated as a neutrophil chemotactic factor. We previously found that LECT2 is an obesity-associated hepatokine that senses liver fat and induces skeletal muscle insulin resistance. In addition, hepatocyte-derived LECT2 activates macrophage proinflammatory activity by reinforcing the lipopolysaccharide (LPS)-induced c-Jun N-terminal kinase signaling. Based on these findings, we examined the effect of LECT2 deletion on nonalcoholic fatty liver disease/nonalcoholic steatohepatitis (NAFLD/NASH) caused by bacterial translocation. We created the bacterial translocation-mediated NAFLD/NASH model using LECT2 knockout mice (LECT2 KO) with 28 times a low-dose LPS injection under high-fat diet feeding conditions. LECT2 deletion exacerbated steatosis and significantly reduced p38 phosphorylation in the liver. In addition, LECT2 deletion increased macrophage infiltration with decreased M1/M2 ratios. LECT2 might contribute to protecting against lipid accumulation and macrophage activation in the liver under pathological conditions, which might be accomplished via p38 phosphorylation. This study provides novel aspects of LECT2 in the bacterial translocation-mediated NAFLD/NASH model., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com. See the journal About page for additional terms.)

Background: Limited research has investigated the relationship between small airway dysfunction (SAD) and static lung hyperinflation (SLH) in patients with post-acute sequelae of COVID-19 (PASC) especially dyspnea and fatigue., Methods: 64 patients with PASC were enrolled between July 2020 and December 2022 in a prospective observational cohort. Pulmonary function tests, impulse oscillometry (IOS), and symptom questionnaires were performed two, five and eight months after acute infection. Multivariable logistic regression models were used to test the association between SLH and patient-reported outcomes., Results: SLH prevalence was 53.1% (34/64), irrespective of COVID-19 severity. IOS parameters and circulating CD4/CD8 T-cell ratio were significantly correlated with residual volume to total lung capacity ratio (RV/TLC). Serum CD8 + T cell count was negatively correlated with forced expiratory volume in the first second (FEV 1 ) and forced vital capacity (FVC) with statistical significance. Of the patients who had SLH at baseline, 57% continued to have persistent SLH after eight months of recovery, with these patients tending to be older and having dyspnea and fatigue. Post-COVID dyspnea was significantly associated with SLH and IOS parameters R5-R20, and AX with adjusted odds ratios 12.4, 12.8 and 7.6 respectively. SLH was also significantly associated with fatigue., Conclusion: SAD and a decreased serum CD4/CD8 ratio were associated with SLH in patients with PASC. SLH may persist after recovery from infection in a substantial proportion of patients. SAD and dysregulated T-cell immune response correlated with SLH may contribute to the development of dyspnea and fatigue in patients with PASC., (© 2024. The Author(s).)

Objectives: To evaluate the safety and effectiveness of chemoembolization for hepatocellular carcinoma (HCC) with portal vein tumour thrombosis (PVTT) confined to a monosegment of the liver., Methods: A total of 192 treatment-naive patients who received chemoembolization between March 2008 and January 2023 as a first-line treatment for locally advanced HCC with PVTT limited to a monosegment were retrospectively analysed. Overall survival (OS) and the identification of pretreatment risk factors related to OS were investigated using Cox regression analysis. Complications, radiologic tumour response, and progression-free survival (PFS) following chemoembolization were investigated., Results: After chemoembolization, the 1-, 3-, and 5-year OS rates were 86%, 48%, and 39%, respectively, and the median OS was 33 months. Multivariable analyses revealed four significant pretreatment risk factors: infiltrative HCC (P = .02; HR, 1.60), beyond the up-to-11 criteria (P = .002; HR, 2.26), Child-Pugh class B (P = .01; HR, 2.35), and serum AFP ≥400 ng/mL (P = .01; HR, 1.69). The major complication rate was 5%. Of the 192 patients, 1 month after chemoembolization, 35% achieved a complete response, 47% achieved a partial response, 11% had stable disease, and 7% showed progressive disease. The median PFS after chemoembolization was 12 months., Conclusions: Chemoembolization shows high safety and efficiency, and contributes to improved survival in patients with HCC with PVTT confined to a monosegment. Four risk factors were found to be significantly associated with improved survival rates after chemoembolization in patients with HCC with PVTT confined to a monosegment., Advances in Knowledge: (1) Although systemic therapy with a combination of atezolizumab and bevacizumab (Atezo-Bev) is recommended as the first-line treatment when HCC invades the portal vein, chemoembolization is not infrequently performed in HCC cases in which tumour burden is limited. (2) Our study cohort (n=192) had a median OS of 33 months and a 5% major complication rate following chemoembolization, findings in the range of candidates typically accepted as ideal for chemoembolization. Thus, patients with HCC with PVTT confined to a monosegment may be good candidates for first-line chemoembolization., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Institute of Radiology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Glucose lowering independently reduces liver fibrosis in human nonalcoholic fatty liver disease. This study investigated the impact of diabetes on steatohepatitis and established a novel mouse model for diabetic steatohepatitis. Male C57BL/6J mice were fed a 60% high-fat diet (HFD) and injected with carbon tetrachloride (CCl 4 ) and streptozotocin (STZ) to induce diabetes. The HFD+CCl 4 +STZ group showed more severe liver steatosis, hepatocyte ballooning, and regenerative nodules compared with other groups. Diabetes up-regulated inflammatory cytokine-associated genes and increased the M1/M2 macrophage ratios in the liver. Single-cell RNA sequencing analysis of nonparenchymal cells in the liver showed that diabetes reduced Kupffer cells and increased bone marrow-derived recruited inflammatory macrophages, such as Ly6C hi -RM. Diabetes globally reduced liver sinusoidal endothelial cells (LSECs). Furthermore, genes related to the receptor for advanced glycation end products (RAGE)/Toll-like receptor 4 (TLR4) were up-regulated in Ly6C hi -RM and LSECs in mice with diabetes, suggesting a possible role of RAGE/TLR4 signaling in the interaction between inflammatory macrophages and LSECs. This study established a novel diabetic steatohepatitis model using a combination of HFD, CCl 4 , and STZ. Diabetes exacerbated steatosis, hepatocyte ballooning, fibrosis, regenerative nodule formation, and the macrophage M1/M2 ratios triggered by HFD and CCl 4 . Single-cell RNA sequencing analysis indicated that diabetes activated inflammatory macrophages and impairs LSECs through the RAGE/TLR4 signaling pathway. These findings open avenues for discovering novel therapeutic targets for diabetic steatohepatitis., (Copyright © 2024 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)

Background and Objectives: Background: Static lung hyperinflation (SLH) measured using body plethysmography in patients with asthma is associated with poor outcomes. The severity of SLH may be associated with small airway dysfunction (SAD), which can be measured using impulse oscillometry (IOS). Objective: This study aims to determine the correlation between SLH and SAD in patients with severe asthma and assess the improvement in SLH and SAD with treatment., Methods: We analyzed data from patients who were enrolled in the Taiwan Severe Asthma Registry, which comprises a prospective observational cohort. Plethysmography and IOS were performed regularly. The relationship between spirometry and IOS parameters was determined. Changes in the clinical outcomes in response to treatment were analyzed., Results: Of 107 patients with severe asthma, 83 (77.6%) had SLH based on an increased residual volume to total lung capacity ratio (RV/ TLC). Most patients were older women with worse pulmonary function and SAD than those without SLH. SAD, defined as increased airway resistance/reactance, was significantly correlated with SLH. Airway reactance at 5 Hz (X5) ≤-0.21 kPa/(L/s) detected SLH with an area under the receiver operating characteristic curve of 0.84 (P<.0001; sensitivity, 85.2%; and specificity, 83.3%). After 12 months, patients who received add-on biologics (vs those who did not) had significantly reduced exacerbations, fractional exhaled nitric oxide level, and blood eosinophil counts, as well as improved forced expiratory volume in the first second, X5, and a trend toward reduced RV/TLC ratio., Conclusions: In severe asthma, airway reactance (X5) could be a novel parameter for assessing SLH.

Background: SARS-CoV-2 spike proteins (SP) can bind to the human angiotensin-converting enzyme 2 (ACE2) in human pulmonary alveolar epithelial cells (HPAEpiC) and trigger an inflammatory process. Angiotensin-(1-7) may have an anti-inflammatory effect through activation of Mas receptor. This study aims to investigate whether SARS-CoV-2 SP can induce inflammation through ACE2 in the alveolar epithelial cells which can be modulated through angiotensin-(1-7)/Mas receptor axis., Methods: HPAEpiC were treated with SARS-CoV-2 SP in the presence or absence of ACE2 antagonist-dalbavancin and Mas receptor agonist-angiotensin-(1-7). Proinflammatory cytokine production (IL-6 and IL-8) were measured at mRNA and protein levels. MAP kinase phosphorylation and transcription factor activation was determined by Western Blot. Mas receptor was blocked by either antagonist (A779) or knockdown (specific SiRNA). Experiments were replicated using A549 cells., Findings: SARS-CoV-2 SP (5 μg/mL) significantly induced MAP kinase (ERK1/2) phosphorylation, downstream transcription factor (activator protein-1, AP-1) activation and cytokine production (IL-6 and IL-8) at both mRNA and protein levels. Pretreatment with dalbavancin (10 μg/mL), or angiotensin-(1-7) (10 μM) significantly reduced ERK1/2 phosphorylation, AP-1 activation, and cytokine production. However, these angiotensin-(1-7)-related protective effects were significantly abolished by blocking Mas receptor with either antagonist (A799,10 μM) or SiRNA knockdown., Interpretation: SARS-CoV-2 SP can induce proinflammatory cytokine production, which can be inhibited by either ACE2 antagonist or Mas receptor agonist-angiotensin-(1-7). Angiotensin-(1-7)-related protective effect on cytokine reduction can be abolished by blocking Mas receptor. Our findings suggest that ACE2/angiotensin-(1-7)/Mas axis may serve as a therapeutic target to control inflammatory response triggered by SARS-CoV-2 SP., Competing Interests: Declaration of competing interest The authors have no conflicts of interest., (Copyright © 2023. Published by Elsevier B.V.)

Objectives: To evaluate the safety and efficacy of chemoembolization in patients with intermediate-stage infiltrative Hepatocellular carcinoma (HCC)., Materials and Methods: This retrospective study evaluated outcomes in treatment-naïve patients who received chemoembolization as first-line treatment for intermediate-stage infiltrative HCC between 2002 and 2022. Of the 2029 treatment-naïve patients who received chemoembolization as first-line treatment for intermediate-stage HCC, 244 (12%) were identified as having the infiltrative type. After excluding two patients lost to follow-up, 242 patients were evaluated., Results: Median post-chemoembolization overall survival (OS) was 16 months. Multivariable Cox analysis identified four factors predictive of OS: Child-Pugh class B (hazard ratio [HR], 1.84; p = 0.001), maximal tumor size ≥ 10 cm (HR, 1.67; p < 0.001), tumor number ≥ 4 (HR, 1.42; p = 0.037), and bilobar tumor involvement (HR, 1.64; p = 0.003). These four factors were used to create pretreatment prediction models, with risk scores of 0-1, 2-4, and 5-7 defined as low, intermediate, and high risk, respectively. Median OS times in these three groups were 34, 18, and 8 months, respectively (p < 0.001). The objective tumor response rate following chemoembolization was 53%. The major complication rate was 9% overall and was significantly higher in the high-risk group (22%) than in the low (2%) and intermediate (3%) risk groups (p < 0.001)., Conclusion: Chemoembolization is safe and effective in selected patients with intermediate-stage infiltrative HCC. Chemoembolization is not recommended in high-risk patients with intermediate-stage infiltrative HCC because of poor OS and high rates of major complications., Clinical Relevance Statement: A pretreatment prediction model was developed using four risk factors associated with overall survival following chemoembolization for intermediate-stage infiltrative hepatocellular carcinoma. This model may provide valuable information for clinical decision-making., Key Points: • Four risk factors (Child-Pugh score B, maximal tumor size ≥ 10 cm, tumor number ≥ 4, and bilobar tumor involvement) were used to create pretreatment prediction models, with risk scores of 0-1, 2-4, and 5-7 defined as low, intermediate, and high risk, respectively. • Median overall survival (OS) times and major complication rate in these three groups were 34, 18, and 8 months, and 2%, 3%, and 22%, respectively (p < 0.001). Chemoembolization is not recommended in high-risk patients with intermediate-stage infiltrative Hepatocellular carcinoma (HCC) because of poor OS and high rates of major complications., (© 2023. The Author(s), under exclusive licence to European Society of Radiology.)

Taiwan has been an aging society since 2018. As a result, long-term care, end-of-life autonomy, and hospice care have received increasing attention. The government of Taiwan promotes home-based healthcare through the National Health Insurance System to enable the efficient utilization of medical resources and reduce overall medical costs. Taiwan's community hospice and palliative care network is expected to serve as the main care model supplementing partial hospitalization and institutional care. In this article, we review the history of and policies related to hospice and palliative care in Taiwan using a literature review and examining Pingtung County as a case study. The implementation of home-based palliative care is also outlined and policy revisions are proposed. The results are intended to provide a reference for healthcare authorities and medical institutions to promote community hospice and palliative care policies. The integrated care model can enhance the capacity of community-based palliative care, support patients receiving palliative care and their family members and caregivers, and ensure physical and psychological comfort for patients. This model contributes to the realization of older adults' preference for dying at home, which is especially pronounced in cultures where traditional Chinese ideas are deeply rooted.

Objectives: Many studies showed better outcomes of endoscopic ultrasound-guided gallbladder drainage (EUS-GBD) when compared with percutaneous transhepatic gallbladder drainage (P-GBD) in which most tubes were left in situ. However, no studies have directly compared EUS-GBD with P-GBD after tube removal (ex situ). We compared the long-term outcomes of EUS-GBD and ex situ or in situ P-GBD in high surgical risk patients with acute cholecystitis., Methods: We reviewed the records of 182 patients (EUS-GBD, n = 75; P-GBD, n = 107) who underwent gallbladder drainage. The procedural outcomes, long-term outcomes, and adverse events were compared., Results: The EUS-GBD group and the P-GBD group had similar rates of technical and clinical success. Early adverse events were less common in the EUS-GBD group (5.5% vs. 18.9%, P = 0.010). The long-term outcomes were evaluated in 168 patients (EUS-GBD, n = 67; P-GBD ex situ, n = 84; P-GBD in situ, n = 17). The rate of cholecystitis recurrence in the EUS-GBD group (6.0%) was similar to that in the P-GBD ex situ group (9.6%, P = 0.422), but significantly lower than that in the P-GBD in situ group (23.5%, P = 0.049). P-GBD in situ was a significant predictor of recurrent cholecystitis (hazard ratio 14.6; 95% confidence interval 2.9-72.8)., Conclusion: The long-term recurrence rate of acute cholecystitis in patients who underwent EUS-GBD was comparable to that in patients whose P-GBD could be removed. However, patients in whom P-GBD could not be removed showed higher rates of recurrent cholecystitis than patients with EUS-GBD., (© 2022 Japan Gastroenterological Endoscopy Society.)

Objectives: To evaluate the safety and efficacy of TACE and factors predicting survival in patients with advanced hepatocellular carcinoma (HCC) without macrovascular invasion (MVI) or extrahepatic spread (EHS)., Methods: This single-center retrospective study included 236 treatment-naïve patients who underwent TACE as first-line treatment for advanced HCC without MVI or EHS between January 2007 and December 2021., Results: Following TACE, the median overall survival (OS) was 24 months. Multivariate Cox regression analyses revealed that tumor number ≥4 (risk point: 3), maximal tumor size >10 cm (risk point: 2), Child-Pugh class B (risk point: 2), alpha-fetoprotein (AFP) concentration ≥400 ng/mL (risk point: 2), and presence of HCC rupture (risk point: 2) were risk factors significantly associated with OS. The expected median OS among patients with <2, 2-4, and 5-9 risk points were 72, 29, and 12 months respectively. The major complication rates were significantly lower in patients with maximal tumor size ≤10 cm than in those with maximal tumor size >10 cm (4% [5/138] vs 21% [21/98], p = 0.001)., Conclusion: TACE may be safe and effective in selected patients with advanced HCC without MVI or EHS, with a median OS of 24 months. Patients with limited tumor burden, compensated liver function, absence of HCC rupture, and favorable biologic markers may benefit the most from TACE. TACE is not recommended for patients with huge HCCs (>10 cm) because of its high rate of major complications (21%)., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Kim, Kim, Yoon, Ko, Shin, Gwon, Ko, Chu, Kim, Kim, Kim and Aljerdah.)

Aims: Transforming growth factor-β2 (TGF-β2) plays an important role in pleiotropic functions and has been reported to be involved in the pathogenesis of chronic obstructive lung disease. The role of TGF-β2 in regulating cigarette smoke (CS)-induced lung inflammation and injury has not been investigated, and its underlying mechanism remains unclear., Main Methods: Primary bronchial epithelial cells (PBECs) were treated with cigarette smoke extract (CSE), and the signaling pathway of TGF-β2 regulating lung inflammation was investigated. Mice were exposed to CS and treated with TGF-β2 i.p. or bovine whey protein extract containing TGF-β2 p.o., and the role of TGF-β2 in alleviating lung inflammation/injury was studied., Key Findings: In vitro, we demonstrated that TGF-β2 attenuated CSE-induced IL-8 production from PBECs through the TGF-β receptor I (TGF-βRI), Smad3, and mitogen-activated protein kinase signaling pathways. Selective TGF-βRI inhibitor (LY364947) and antagonist of Smad3 (SIS3) abolished the effect of TGF-β2 on alleviating CSE-induced IL-8 production. In vivo, CS exposure for 4 weeks in mice increased the levels of total protein, inflammatory cell counts, and monocyte chemoattractant protein-1 in bronchoalveolar fluid and induced lung inflammation/injury, as revealed by immunohistochemistry. Administration of TGF-β2 through intraperitoneal injection or oral feeding with bovine whey protein extract containing TGF-β2 significantly reduced CS-induced lung inflammation and injury., Significance: We concluded that TGF-β2 reduced CSE-induced IL-8 production through the Smad3 signaling pathway in PBECs and alleviated lung inflammation/injury in CS-exposed mice. The anti-inflammatory effect of TGF-β2 on CS-induced lung inflammation in humans deserves further clinical study., Competing Interests: Declaration of competing interest The authors declare that there is no conflict of interest regarding the publication of this paper., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives: To compare the safety and efficacy of balloon-occluded transarterial chemoembolization (B-TACE) and conventional TACE (C-TACE) in treating single hepatocellular carcinoma (HCC)., Methods: This single-center retrospective study included 523 patients who underwent C-TACE and 44 who underwent B-TACE as first-line treatment for single HCCs between November 2017 and December 2019. After propensity score matching (PSM), initial tumor response rates, local tumor progression (LTP), and major complication rates were evaluated in the 32 pairs of PSM matched population., Results: In the 32 pairs of PSM cohort, B-TACE showed distinct superiority over C-TACE in treating single HCCs, with significantly higher initial complete response (CR) rates (93.8% vs. 62.5%, p = 0.005). During a median follow-up of 37 months (range, 12.7-46.5 months), 13 patients (40.6%) who underwent B-TACE and 16 (50%) who underwent C-TACE showed LTP of treated lesions. Size-based sub-group analysis showed that the median times to LTP in patients with medium- to large-sized tumors (> 3 cm) were significantly longer in the B-TACE (27 months; 95% confidence interval [CI], 19.7-34.3 months) than in the C-TACE (13 months; 95% CI, 3.9-22.1 months) group (p = 0.019). The major complication rate was similar between the two groups., Conclusions: B-TACE had a higher initial CR rate than C-TACE in treating single HCCs. Moreover, size-based subgroup analysis showed that time to LTP was significantly longer in patients with medium- to large-sized HCCs (> 3 cm) who underwent B-TACE rather than C-TACE., Key Points: • B-TACE was superior to C-TACE in treating single HCC, with a significantly higher initial complete response rate after one session of treatment. • In size-based subgroup analysis, time to LTP was significantly longer in patients with medium- to large-sized HCCs (>3 cm) who underwent B-TACE rather than C-TACE. • B-TACE should be considered an alternative treatment option for medium- to large-sized single HCCs (>3 cm) in patients with a nonresectable condition and those who prefer nonsurgical treatment., (© 2022. The Author(s), under exclusive licence to European Society of Radiology.)

Background: Young people often experience dramatic changes, both psychologically and physically, as they are transiting from students to working adults. However, there is still a lack of empirical studies on the relationship between the trait emotional intelligence and the career adaptability of youths in the Asia-Pacific region. This research examines that relationship in Chinese youths in Hong Kong., Method: Cross-sectional data (N = 500) was collected from two universities in 2019 and 2020. The 2019 sample was made up of 256 Chinese university students (117 males, 139 females; ages 21-25). The 2020 sample included 244 Chinese university students (132 males, 112 females; ages 21-25). The participants were asked to complete the Wong and Law Emotional Intelligence Scale (WLEIS) to evaluate their emotional intelligence in the domains of self-emotion appraisal, other people's emotion appraisal, regulation of emotion, and use of emotion. Participants completed the Career Adapt-Abilities Scale (CAAS) to assess their career adaptability in the areas of concern, control, curiosity, and confidence., Results: All domains of trait emotional intelligence were positively associated with career adaptability. Multiple Regression analysis showed that self-emotion appraisal and appraisal of other people's emotional were the most predictive factors in terms of career adaptability. Together, these two dimensions of emotional intelligence explain 12.5%, 26.2%, 13.4% and 69.4% respectively of the variance in students' concern, control, curiosity, and confidence in relation to career adaptability., Conclusion: The results highlight the importance of emotional intelligence in career adaptability. It is thus of value to study further whether career adaptability of young people may improve if emotional intelligence is incorporated into the student curriculum. The findings offer valuable insights for educators and teachers who are responsible for well-rounded development of students, and will thereby foster healthy lifestyles, stable emotional well-being and greater career adaptability in adolescents., (© 2023. The Author(s).)

This study aims to determine the effect of service learning (SL) on the trait emotional intelligence and adversity quotient of Chinese undergraduate students in Hong Kong. The SL programme lasted six months (at least 80 service hours). In a pre-test-post-test experimental design, students who participated in the SL during that time period were classified as the experimental group ( n = 139; 69 male, 70 female), whereas students who never participated in SL were classified as the comparison group ( n = 133; 66 male, 67 female). Both groups of participants were asked to finish the Wong and Law Emotional Intelligence Scale (WLEIS) and the Adversity Response Profile ® (ARP) before and after the SL programme. The results showed that there were no significant differences in WLEIS and ARP scores (at the pre-test) between the experimental and comparison groups. The results further revealed that students in the experimental group had better improvements in WLEIS and ARP than those in the comparison group after they completed SL. These findings provide valuable insights and implications for incorporating components of SL into interventions for youths to improve their ability to process emotions and overcome adversity.

Background: Ethical dilemmas that arise in the clinical setting often require the collaboration of multiple disciplines to be resolved. However, medical and nursing curricula do not prioritize communication among disciplines regarding this issue. A common teaching strategy, problem-based learning, could be used to enhance communication among disciplines. Therefore, a university in southern Taiwan developed an interprofessional ethics education program based on problem-based learning strategies. This study described tutors' experience teaching in this program., Aim: To explore the phenomenon of teaching and learning in interprofessional ethics education for medical and nursing students from the perspectives of tutors., Design: Phenomenological qualitative research., Methods: Medical and nursing students completed a 6-week interprofessional ethics education program moderated by either physician or nurse tutors. At the conclusion of the ethics education program, all 14 tutors were invited to participate in focus group interviews. Among them, six tutors (three nursing tutors and three physician tutors) participated in additional individual interviews. All of the contents from the focus group interviews and individual interviews were recorded and transcribed. Using the phenomenological approach, the phenomenon of teaching and learning in interprofessional ethics education were generated., Ethical Consideration: The study was approved by the Institutional Review Board., Findings: Three themes emerged from the tutors' teaching perspectives, including the instructor's motivation to teach, the use of narrative case scenarios, and the emphasis on improving interprofessional ethics communication., Discussion: Problem-based learning creates an interprofessional communication platform in interprofessional ethics education. The phenomenon of value convergence between tutors and students, between different students' professions, and between different students' professional maturities is observed., Conclusion: Problem-based learning is an effective teaching strategy for creating a communication platform for interprofessional ethics education. Ethic curriculum should emphasize motivating instructor, use narrative case scenarios, and focus on interprofessional communication.

Patients with asthma are treated in primary healthcare facilities (PHCFs) in Taiwan, where the asthma control status associated with acute exacerbation (AE) and use of oral corticosteroids (OCS) and short-acting β2-agonist (SABA) inhalers remains unclear. A cross-sectional, close-ended, face-to-face questionnaire survey invited board-certified physicians who treat adult asthma patients in PHCFs. The contents of the questionnaire included three parts: rescue OCS to treat AE, regular OCS for asthma control, and AE-related adverse outcomes. There were 445 out of 500 physicians who completed the questionnaire, with 61% of them being non-pulmonologists. A substantial proportion of asthma patients needed rescue OCS or regular OCS each month, or ≥3 canisters of SABA inhalers per year. Approximately 86% of physicians reported their patients with ≥2 AE-related unscheduled visits to clinics or emergency departments in the past year. A total of 41% of physicians reported their patients receiving intubation or intensive care in the past year. A total of 92% of physicians prescribed rescue OCS ≤ 40 mg/day. A total of 92% of physicians prescribed rescue OCS for a duration of ≤7 days for AEs. A total of 85% of physicians prescribed regular OCS ≤ 10 mg/day for asthma control. This is the first study to present the perceptions of asthma-treating physicians on the use of OCS in PHCFs. In summary, 31% of physicians reported ≥ 6% of their patients needed OCS for asthma control and 41% of physicians reported their patients with adverse outcomes in the past year. Thus, the need to improve asthma control in Taiwan is suggested by our study results.

Cancer-related fatigue is the most common and longest-lasting symptom of discomfort experienced by cancer patients. Its effects on patients include physical, psychological, emotional, and cognitive stress, which greatly reduce quality of life. The field of mind-body integrated medicine has improved gradually in recent years, with many evidence-based studies supporting the efficacy of mindfulness as a symptom management strategy for cancer-related fatigue. Based on a review of the literature, this paper introduces the definition of cancer-related fatigue and related assessments and treatments, describes the origin of mindfulness and related concepts, and introduces mindfulness-based empirical treatment strategies for cancer-related fatigue, including mindfulness-based stress reduction and mindfulness-based cognitive therapy, and their effects. The findings are intended to provide clinicians with a reference for the future care of patients with cancer-related fatigue.

Background: Previous studies have evaluated the competency of newly graduated nurses and nurses. However, most of the instruments used include a large number of items that make completing them a time-consuming process. A brief instrument may be more acceptable and feasible for use in these evaluations., Purpose: This study was designed to develop the brief capstone core competency (CCC or 3C) scale and validate its effectiveness in evaluating the academic and practical performance of nursing students enrolled in a bachelor's degree program., Methods: A cross-sectional study was conducted. The 3C scale was developed in two phases. In Phase I, the items were summed from literature reviews, an expert panel, known-groups validity, test-retest reliability, internal consistency reliability, and exploratory factor analysis. In Phase II, the efficacy of the instrument was confirmed using confirmative factor analysis. Five hundred ninety-six participants participated in the first phase, and 520 participants participated in the second phase. The study period was 2016-2017., Results: The 3C scale includes 24 items distinguished into a three-component structure that accounts for 67.85% of the total variance. The three components include nursing intelligence, nursing humanity, and nursing career. The 3C scale was found to have high levels of internal consistency reliability (.97) and test-retest stability reliability ( r = .97). A significant statistical difference in the performance level was examined between senior and junior nursing students. The hypothesized three-factor model fit index showed χ 2 / df = 1338.25/249, p < .001, goodness-of-fit index = .82, comparative fit index = .90, root mean square error of approximation = .09, and standardized root mean square residual = .06. The participants were found to have excellent nursing humanity competency., Conclusions: The developed 3C scale exhibited satisfactory reliability and validity for use with nursing students. The 3C scale may be used to evaluate the performance of nursing students during their learning process, and the results may be used to evaluate changes in educational outcomes., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2022 The Authors. Published by Wolters Kluwer Health, Inc.)

Selenoprotein P is upregulated in type 2 diabetes, causing insulin and exercise resistance. We have previously reported that eicosapentaenoic acid (EPA) negatively regulates Selenop expression by suppressing Srebf1 in H4IIEC3 hepatocytes. However, EPA downregulated Srebf1 long before downregulating Selenop. Here, we report additional novel mechanisms for the Selenop gene regulation by EPA. EPA upregulated Foxo1 mRNA expression, which was canceled with the ERK1/2 inhibitor, but not with the PKA inhibitor. Foxo1 knockdown by siRNA initiated early suppression of Selenop, but not Srebf1, by EPA. However, EPA did not affect the nuclear translocation of the FoxO1 protein. Neither ERK1/2 nor PKA inhibitor affected FoxO1 nuclear translocation. In summary, FoxO1 knockdown accelerates the EPA-mediated Selenop downregulation independent of SREBP-1c in hepatocytes. EPA upregulates Foxo1 mRNA via the ERK1/2 pathway without altering its protein and nuclear translocation. These findings suggest redundant and conflicting transcriptional networks in the lipid-induced redox regulation.

Background: Identifying positive bronchodilator reversibility (BDR) helps the diagnosis of asthma. However, not all patients can adequately perform the forced expiration during the spirometry test. An alternative test is required. Impulse oscillometry (IOS) is an effort-independent technique that enables the measurement of lung mechanics during quiet tidal breathing. We investigated the potentiality of IOS to evaluate BDR in untreated adult patients with newly diagnosed asthma (UAPNDS)., Methods: All UAPNDS (aged 20-80 years) who never smoke and underwent IOS and spirometry before and after salbutamol inhalation at their initial visit to the hospital from March 22, 2017, to December 31, 2019, were identified. A total of 323 patients were enrolled. Data from the medical record, including demographic characteristics, laboratory examination, spirometric data, and IOS parameters, were retrospectively reviewed. The associations of parameters with the positive BDR and the performance of parameters in predicting the positive BDR were evaluated by statistical methods., Results: Patients (n = 323) had a median age of 64 years and were mostly female (67.5%). Several variables, including serum total immunoglobulin level, blood eosinophil counts, blood eosinophil percentage (%), and two IOS parameters, were found to be different between the positive (n = 93) and negative BDR (n = 230) groups. Multivariate logistic regression analyses after adjustment by cofactors revealed that the percentage change of the area under the reactance curve between 5 Hz and resonant frequency [ΔAx (%)] after salbutamol inhalation was the only independent factor for the positive BDR. The area under the receiver operating characteristic curve of ΔAx (%) in predicting the positive BDR was 0.614 ( p = 0.0013), and its optimal cutoff value was -53.8% (sensitivity, 39.78% and specificity, 80.43%)., Conclusion: In addition to spirometry, ΔAx (%), an IOS parameter, may serve as a novel indicator to evaluate BDR in UAPNDS., Competing Interests: Conflicts of interest: Dr. Diahn-Warng Perng, an editorial board member at Journal of the Chinese Medical Association, had no role in the peer review process of or decision to publish this article. The other authors declare that they have no conflicts of interest related to the subject matter or materials discussed in this article., (Copyright © 2022, the Chinese Medical Association.)

Introduction: Chronic obstructive pulmonary disease (COPD) with eosinophilic airway inflammation represents a distinct phenotype that might respond to treatment with inhaled corticosteroids. Fractional exhaled nitric oxide (FENO) might predict eosinophilic inflammation and guide treatment option. We hypothesized that COPD patients with different baseline levels of FENO might have differentiated response to treatment with salmeterol/fluticasone (SFC) or tiotropium (TIO)., Methods: This open-label, randomized-controlled trial enrolled treatment-naïve COPD patients who were stratified into high- (≥23.5ppb) and low-FENO group, followed by 12-week treatment with SFC or TIO. A linear mixed model with repeated measures was applied to analyze the changes in FENO (primary outcome), COPD assessment test (CAT) score, FEV 1 , and parameters in induced sputum and blood after treatment., Results: 134 patients were divided into 4 subgroups: low-FENO/SFC (n=30), low-FENO/TIO (n=29), high-FENO/SFC (n=37), and high-FENO/TIO (n=38). At baseline, FENO 23.5ppb clearly differentiated between eosinophilic and non-eosinophilic inflammation groups based on the eosinophils in induced sputum and blood. FENO significantly correlated with sputum and blood eosinophils at baseline. High-FENO/SFC (vs. high-FENO/TIO) subgroup had significant reduction in FENO and sputum inflammation profiles (including eosinophils, macrophages, matrix metalloproteinase-9, and interlukin-8) after treatment. These differences were not replicated between low-FENO/SFC and low-FENO/TIO subgroups. The improvement in CAT and FEV 1 after treatment was indiscriminate between SFC and TIO in the low- and high-FENO groups., Conclusion: High baseline FENO can serve as an indicator of eosinophilic airway inflammation in COPD patients who may respond favorably to treatment with inhaled corticosteroids/long-acting β 2 -agonists., Trial Registration Number: ClinicalTrials.gov Identifier: NCT02546349., (Copyright © 2021 The Authors. Published by Elsevier España, S.L.U. All rights reserved.)

Cyclosporine A (CsA) is an immunosuppressant applied worldwide for preventing graft rejection and autoimmune diseases. However, CsA elevates oxidative stress, which can lead to liver injuries. The present study aimed to clarify the mechanisms underlying the CsA-mediated oxidative stress. Among the redox proteins, CsA concentration-dependently downregulated Selenop -encoding selenoprotein P, a major circulating antioxidant protein reducing reactive oxygen species, in hepatocytes cell lines and primary hepatocytes. The luciferase assay identified the CsA-responsive element in the SELENOP promoter containing a putative binding site for forkhead box protein O (FoxO) 1. The CsA-mediated suppression on the SELENOP promoter was independent of the nuclear factor of activated T-cell, a classic target repressed by CsA. A chromatin immunoprecipitation assay showed that CsA suppressed the FoxO1 binding to the SELENOP promoter. Foxo1 knockdown significantly downregulated Selenop expression in H4IIEC3 cells. Furthermore, CsA downregulated FoxO1 by inactivating its upstream signal transducer and activator of transcription 3 (STAT3). Knockdown of Stat3 downregulated Foxo1 and Selenop expression in hepatocytes. These findings revealed a novel mechanism underlying CsA-induced oxidative stress by downregulating the STAT3-FoxO1- Selenop pathway in hepatocytes. SIGNIFICANCE STATEMENT: This study shows that Cyclosporine A (CsA) downregulates Selenop , an antioxidant protein, by suppressing the signal transducer and activator of transcription 3-forkhead box protein O1 pathway in hepatocytes, possibly one of the causations of CsA-induced oxidative stress in hepatocytes. The present study sheds light on the previously unrecognized CsA-redox axis., (Copyright © 2022 by The American Society for Pharmacology and Experimental Therapeutics.)

The purpose of this study was to compare the efficacy and safety of surgical resection (SR) plus intraoperative radiofrequency ablation (IORFA) with transarterial chemoembolization (TACE) in patients with intermediate-stage HCC and Child-Pugh class A liver function. Treatment-naïve patients who received SR plus IORFA ( n = 104) or TACE ( n = 513) were retrospectively evaluated. Patients were subjected to a maximum 1:3 propensity score matching (PSM), yielding 95 patients who underwent SR plus IORFA and 252 who underwent TACE. Evaluation of the entire study population showed that progression-free survival (PFS) and overall survival (OS) were significantly better in the SR plus IORFA than in the TACE group. After PSM, the median PFS (18.4 vs. 15.3 months) and OS (88.6 vs. 56.2 months) were significantly longer, and OS rate significantly higher (HR: 0.65, p = 0.026), in the SR plus IORFA group than in the TACE group. Stratified Cox regression analysis and doubly robust estimation revealed that treatment type was significantly associated with both OS and PFS. Rates of major complications were similar in the SR plus IORFA and TACE groups. In conclusion, SR plus IORFA showed better survival outcomes than TACE. SR plus IORFA may provide curative treatment to patients with intermediate-stage HCC with ≤4 tumors and Child-Pugh class A.

Selenoprotein P (SeP; encoded by SELENOP in humans, Selenop in rodents) is a hepatokine that is upregulated in the liver of humans with type 2 diabetes. Excess SeP contributes to the onset of insulin resistance and various type 2 diabetes-related complications. We have previously reported that the long-chain saturated fatty acid, palmitic acid, upregulates Selenop expression, whereas the polyunsaturated fatty acids (PUFAs) downregulate it in hepatocytes. However, the effect of medium-chain fatty acids (MCFAs) on Selenop is unknown. Here we report novel mechanisms that underlie the lauric acid-mediated Selenop gene regulation in hepatocytes. Lauric acid upregulated Selenop expression in Hepa1-6 hepatocytes and mice liver. A luciferase promoter assay and computational analysis of transcription factor-binding sites identified the hepatic nuclear factor 4α (HNF4α) binding site in the SELENOP promoter. A chromatin immunoprecipitation (ChIP) assay showed that lauric acid increased the binding of HNF4α to the SELENOP promoter. The knockdown of Hnf4α using siRNA canceled the upregulation of lauric acid-induced Selenop. Thus, the lauric acid-induced impairment of Akt phosphorylation brought about by insulin was rescued by the knockdown of either Hnf4α or Selenop. These results provide new insights into the regulation of SeP by fatty acids and suggest that SeP may mediate MCFA-induced hepatic insulin signal reduction.

Background: Regulatory bodies have approved five biologics for severe asthma. However, regional differences in accessibility may limit the global potential for personalized medicine., Objective: To compare global differences in ease of access to biologics., Methods: In April 2021, national prescription criteria for omalizumab, mepolizumab, reslizumab, benralizumab, and dupilumab were reviewed by severe asthma experts collaborating in the International Severe Asthma Registry. Outcomes (per country, per biologic) were (1) country-specific prescription criteria and (2) development of the Biologic Accessibility Score (BACS). The BACS composite score incorporates 10 prescription criteria, each with a maximum score of 10 points. Referenced to European Medicines Agency marketing authorization specifications, a higher score reflects easier access., Results: Biologic prescription criteria differed substantially across 28 countries from five continents. Blood eosinophil count thresholds (usually ≥300 cells/μL) and exacerbations were key requirements for anti-IgE/anti-IL-5/5R prescriptions in around 80% of licensed countries. Most countries (40% for dupilumab to 54% for mepolizumab) require two or more moderate or severe exacerbations, whereas numbers ranged from none to four. Moreover, 0% (for reslizumab) to 21% (for omalizumab) of countries required long-term oral corticosteroid use. The BACS highlighted marked between-country differences in ease of access. For omalizumab, mepolizumab, benralizumab, and dupilumab, only two, one, four, and seven countries, respectively, scored equal or higher than the European Medicines Agency reference BACS. For reslizumab, all countries scored lower., Conclusions: Although some differences were expected in country-specific biologic prescription criteria and ease of access, the substantial differences found in the current study present a challenge to implementing precision medicine across the world., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Non-pharmacological treatment with high-flow nasal cannula (HFNC) may play a vital role in treatment of patients with chronic obstructive pulmonary disease (COPD). To evaluate the efficacy of HFNC, impulse oscillation system (IOS) is a new noninvasive technique in measuring the impedance of different portions of lungs. It shows higher sensitivity in contrast to conventional pulmonary function tests (PFT). However, whether IOS is an appropriate technique to evaluate the efficacy of HFNC in improving the impedance of small airways or peripheral lung in patients with COPD is still unclear. We enrolled 26 stable COPD participants randomised into two groups receiving HFNC or nasal cannula (NC) for 10 min followed by a 4-week washout period and crossover alternatively. IOS was used to detect the difference of respiratory impedance after HFNC or NC interventions. IOS parameters, PFT results, transcutaneous partial pressure of carbon dioxide, peripheral oxygen saturation, body temperature, respiratory rate, pulse rate, and blood pressure at the time of pre-HFNC, post-HFNC, pre-NC, and post-NC, were collected and analysed using SPSS (version 25.0, IBM, Armonk, NY, USA). The IOS measurement indicated that HFNC significantly improved R5, R5% predicted, R5-R20, X5-predicted, and Fres compared with NC, whereas no significant difference was observed through the PFT measurement. The beneficial effect of HFNC in improving small airway resistance and peripheral lung reactance compared with that of NC in patients with stable COPD was confirmed through IOS measurement.Trial registration: ClinicalTrials.gov NCT05130112 22/11/2021., (© 2022. The Author(s).)

Reactive oxygen species (ROS) activate uncoupler protein 1 (UCP1) in brown adipose tissue (BAT) under physiological cold exposure and noradrenaline (NA) stimulation to increase thermogenesis. However, the endogenous regulator of ROS in activated BAT and its role in pathological conditions remain unclear. We show that serum levels of selenoprotein P (SeP; encoded by SELENOP) negatively correlate with BAT activity in humans. Physiological cold exposure downregulates Selenop in BAT. Selenop knockout mice show higher rectal temperatures and UCP1 sulfenylation during cold exposure. SeP treatment to brown adipocytes eliminated the NA-induced mitochondrial ROS by upregulating glutathione peroxidase 4 and impaired cellular thermogenesis. A high-fat/high-sucrose diet elevates serum SeP levels and diminishes the elevated NA-induced thermogenesis in BAT-Selenop KO mice. Therefore, SeP is the intrinsic factor inducing reductive stress that impairs thermogenesis in BAT and may be a potential therapeutic target for obesity and diabetes., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: To determine the efficacy and safety of ultrasound (US)-guided sclerotherapy for the treatment of ovarian endometrioma through a systematic review and meta-analysis., Methods: MEDLINE and EMBASE databases were searched for studies reporting outcomes in patients with endometrioma who were treated with US-guided sclerotherapy. Meta-analyses of recurrence, pain resolution, pregnancy, technical success, and complication rates were analyzed. Subgroup analyses were conducted regarding the indwelling time of sclerotherapy (≤ 10 min vs > 10 min)., Results: Twenty-eight studies (1301 patients) were included. The pooled technical efficacy was 98.3%. The pooled estimates of recurrence, pain resolution, and pregnancy rate were 13.8%, 85.9%, and 37.6%, respectively. The pooled major complication rate was 1.7%. A sclerotherapy time > 10 min had a lower pooled recurrence rate than a time ≤ 10 min (11.2% vs 20.9%; p = 0.106). Direct comparisons showed that the recurrence rate was significantly lower with sclerotherapy > 10 min than with sclerotherapy ≤ 10 min (OR, 0.2; p = 0.015). Regarding pregnancy rates, sclerotherapy of > 10 min showed no significant difference compared with sclerotherapy of ≤ 10 min (35.9% vs 38.8%; p = 0.664). Direct comparisons with surgery showed that sclerotherapy increased the pregnancy rate compared with surgery (OR, 2.0; p = 0.042). There was no significant difference in AMH level before and after sclerotherapy (p = 0.951). There was no significant difference in major complication rates between sclerotherapy > 10 min and ≤ 10 min (p = 0.837)., Conclusion: US-guided sclerotherapy seems to be an effective and safe therapeutic option regarding recurrence, pain resolution, and pregnancy for patients with ovarian endometrioma., Key Points: • US-guided sclerotherapy seems to be an effective and safe therapeutic option regarding recurrence, pain resolution, and pregnancy for patients with ovarian endometrioma. • Sclerotherapy of more than 10 min had a lower recurrence rate than sclerotherapy less than or equal to 10 min. There was no significant difference in major complication rates between sclerotherapy of > 10 min and ≤ 10 min. • Future randomized controlled trials are warranted to compare the outcomes of US-guided sclerotherapy with surgery., (© 2021. European Society of Radiology.)

We propose Steadiness and Cohesiveness, two novel metrics to measure the inter-cluster reliability of multidimensional projection (MDP), specifically how well the inter-cluster structures are preserved between the original high-dimensional space and the low-dimensional projection space. Measuring inter-cluster reliability is crucial as it directly affects how well inter-cluster tasks (e.g., identifying cluster relationships in the original space from a projected view) can be conducted; however, despite the importance of inter-cluster tasks, we found that previous metrics, such as Trustworthiness and Continuity, fail to measure inter-cluster reliability. Our metrics consider two aspects of the inter-cluster reliability: Steadiness measures the extent to which clusters in the projected space form clusters in the original space, and Cohesiveness measures the opposite. They extract random clusters with arbitrary shapes and positions in one space and evaluate how much the clusters are stretched or dispersed in the other space. Furthermore, our metrics can quantify pointwise distortions, allowing for the visualization of inter-cluster reliability in a projection, which we call a reliability map. Through quantitative experiments, we verify that our metrics precisely capture the distortions that harm inter-cluster reliability while previous metrics have difficulty capturing the distortions. A case study also demonstrates that our metrics and the reliability map 1) support users in selecting the proper projection techniques or hyperparameters and 2) prevent misinterpretation while performing inter-cluster tasks, thus allow an adequate identification of inter-cluster structure.

Many treatments including antiviral and non-antiviral drugs, and critical care are considered for the management of coronavirus disease 2019 (COVID-19). Practice recommendations need to be updated and graded according to the critical evaluation of rapidly emerging literature. In June 2020, Research Center for Epidemic Prevention-National Yang Ming Chiao Tung University formed a task group comprising infectious disease clinicians, pulmonologists, and intensivists with varied areas of expertise. The steering committee prioritized questions and outcomes. The keywords for the searches were COVID-19 and prone position, extracorporeal membrane oxygenation (ECMO), noninvasive positive pressure ventilation (NIPPV), remdesivir, lopinavir, hydroxychloroquine/chloroquine (HCQ/CQ), azithromycin, corticosteroid, tocilizumab, convalescent plasma therapy, and intravenous immunoglobin (IVIG). A systematic review of peer-reviewed literature was performed by the consensus panel. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used in assessing the certainty of evidence and making recommendations. The effects of COVID-19 treatments on mortality and clinical improvement were summarized in 11 tables, and GRADE was presented to define the strength and quality of evidence for recommendation. The consensus recommended that prone position implanted in COVID-19 patients with hypoxic respiratory failure (IIC), careful selection for the support of ECMO (IIB), NIPPV being feasible but a risk of staff contamination (IIC), remdesivir generally administered in mild-to-moderate COVID-19 patients (IA), the use of dexamethasone in critically ill COVID-19 patients (IA), and the use of tociliziumab in hospitalized severe/critical COVID-19 patient with elevated markers of systemic inflammation (IA). The consensus recommended against the use of lopinavir/ritonavir (IB), HCQ/CQ (IA), azithromycin (IA), convalescent plasma therapy (IA), and IVIG (IA). The inception of the consensus and task group has provided much-needed evidence of the efficacy and safety of various therapies for the management of COVID-19 patients, and make a description about the benefits and harms for most treatments., (Copyright © 2021, the Chinese Medical Association.)

Hypoxia is a universal pathological feature of solid tumors. Hypoxic tumor cells acquire metastatic and lethal phenotypes primarily through the activities of hypoxia-inducible factor 1 alpha (HIF1α). Therefore, HIF1α is considered as a promising therapeutic target. However, HIF inhibitors have not proven to be effective in clinical testing. The underlying mechanism is unclear. We report that oncogenic protein ID1 is upregulated in hypoxia by HIF1α shRNA or pharmacological inhibitors. In turn, ID1 supports tumor growth in hypoxia in vitro and in xenografts in vivo , conferring adaptive survival response and resistance. Mechanistically, ID1 proteins interfere HIF1-mediated gene transcription activation, thus ID1 protein degradation is accelerated by HIF1α-dependent mechanisms in hypoxia. Inhibitions of HIF1α rescues ID1, which compensates the loss of HIF1α by the upregulation of GLS2 and glutamine metabolism, thereby switching the metabolic dependency of HIF1α -inhibited cells from glucose to glutamine., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Geng, Ko, Pittsenbarger, Harvey, Xue, Liu, Wiens, Kachhap, Beer and Qian.)

This is a narrative review of various treatment modalities for advanced hepatocellular carcinoma (HCC), with a focus on recent updates in radiological treatments, as well as novel treatment concepts related to immune checkpoint inhibitors and combination therapies with locoregional treatments. Interventional radiologists have made efforts toward developing alternative and/or combination treatments for first-line systemic treatment of patients with advanced HCC. Locoregional treatments with or without systemic therapy may be considered in the selected patients. Various treatment modalities for advanced HCC are emerging, and several randomized controlled trials, including those of combination treatments with immunotherapy, are ongoing., Competing Interests: The authors have no potential conflicts of interest to disclose., (Copyright © 2021 The Korean Society of Radiology.)

The predictive performance of applying the degree of convexity in expiratory flow-volume (EFV) curves to detect airway obstruction in ventilated patients has yet to be investigated. We enrolled 33 nonsedated and nonparalyzed mechanically ventilated patients and found that the degree of convexity had a significant negative correlation with FEV 1 % predicted. The mean degree of convexity in EFV curves in the chronic obstructive pulmonary disease (COPD) group (n = 18) was significantly higher than that in the non-COPD group (n = 15; 26.37 % ± 11.94 % vs. 17.24 % ± 10.98 %, p = 0.030) at a tidal volume of 12 mL/kg IBW. A degree of convexity in the EFV curve > 16.75 at a tidal volume of 12 mL/kg IBW effectively differentiated COPD from non-COPD (AUC = 0.700, sensitivity = 77.8 %, specificity = 53.3 %, p = 0.051). The degree of convexity calculated from EFV curves may help physicians to identify ventilated patients with airway obstruction., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

Chronic obstructive pulmonary disease (COPD) has significant contributions to morbidity and mortality world-wide. Early symptoms of COPD are not readily distinguishable, resulting in a low rate of diagnosis and intervention. Different guidelines and recommendatations for the diagnosis and treatment of COPD exist globally. The first edition of clinical practice guidelines for COPD was published in 2016 by the Ministry of Health and Welfare in Taiwan in collaboration with the Taiwan evidence-based medicine association and Cochrane Taiwan, and was revised in 2019 in order to update recent diagnostic and therapeutic modalities for COPD and its acute exacerbation. This revised guideline covered a range of topics highlighted in the Global Initiative for Chronic Obstructive Lung Disease (GOLD) report, including strategies for the diagnosis, assessment, monitoring, and management of stable COPD and exacerbations, with particular focus on evidence from Taiwan. The recommendations included in the revised guideline were formed based on a comprehensive systematic review or meta-analysis of specific clinical issues identified by an expert panel that surveyed relevant scientific evidence in the literature and guidelines published by the clinical communities and organizations nationally and internationally. The guidelines and recommendations are applicable to the clinical settings in Taiwan. We expect this revised guideline to facilitate the diagnosis, treatment and management of patients with COPD by physicians and health care professionals in Taiwan. Adaptations of the materials included herein for educational and training purposes is encouraged., (Copyright © 2021 Formosan Medical Association. Published by Elsevier B.V. All rights reserved.)

Background: There are few reports of renal artery embolization (RAE) via transradial access (TRA) for renal hemorrhage, and none have compared outcomes of RAE via TRA and transfemoral access (TFA). The objective was to compare technical and clinical outcomes in patients undergoing RAE via TRA or TFA for iatrogenic renal hemorrhage., Materials and Methods: This study included 45 RAE procedures (16 TRA and 29 TFA) for iatrogenic renal hemorrhage in 43 patients performed at a tertiary referral center between October 2018 and December 2020. Information regarding underlying diseases, coagulation status, angiographic and embolization procedure details, technical and clinical successes, and complications were retrospectively evaluated., Results: There were no differences in demographics, underlying diseases, updated Charlson comorbidity scores, angiographic findings, and volume of contrast material between the TRA and TFA groups. By contrast, prothrombin time and international normalized ratio were significantly lower in the TRA than in the TFA group. Embolic materials differed significantly in the two groups. Procedure duration, fluoroscopy time, digital subtraction angiography number, and dose area product were slightly lower in the TRA than in the TFA group, but the differences were not statistically significant. Technical and clinical success rates in the TRA and TFA groups were 100% and 96.6%, and 100% and 96.6%, respectively. No patient in either group experienced procedure-related complications during a 4 week follow-up period., Conclusion: RAE via TRA in the management of iatrogenic renal hemorrhage was safe and feasible, with similar procedure duration and radiation exposure to RAE via TFA. TRA may be an acceptable alternative to TFA in these patients., Competing Interests: The authors have declared that no competing interests exist.

Severe fever with thrombocytopenia syndrome (SFTS) is a new tick-borne viral disease, and most SFTS virus (SFTSV) infections occur via bites from the tick Haemaphysalis longicornis ; however, SFTSV transmission can also occur through close contact with an infected patient. SFTS is characterized by acute high fever, thrombocytopenia, leukopenia, elevated serum hepatic enzyme levels, gastrointestinal symptoms, and multiorgan failure and has a 16.2 to 30% mortality rate. In this study, we found that age, dyspnea rates, aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase, multiorgan dysfunction score (MODS), viral load, IL-6 levels, and IL-10 levels were higher in patients with fatal disease than in patients with nonfatal disease during the initial clinical course of SFTS. In addition, we found that IL-6 and IL-10 levels, rather than viral load and neutralizing antibody titers, in patients with an SFTSV infection strongly correlated with outcomes (for severe disease with an ultimate outcome of recovery or death)., Competing Interests: K-AH was employed by SML Genetree. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Yoo, Kim, Heo, Hwang, Oh, Ha, Ko, Baek, Kim, Kim, Lee, Kang, Yoo, Kim, Lee and Lee.)

The purpose of this study was to define the role of transcatheter arterial chemoembolization (TACE) in patients with a single large hepatocellular carcinoma (HCC) and define the patient groups benefiting from TACE. Treatment-naïve patients with preserved liver function who received TACE as the first-line treatment for single large (>5 cm) HCC without macrovascular invasion and extrahepatic metastasis between 2007 and 2019 were retrospectively analyzed. Overall survival, progression-free survival, radiologic tumor response, complications, and predictors of survival were analyzed using multivariate analysis, and then a pretreatment risk-prediction model was created using the four predictive factors of tumor size, tumor type, ALBI grade, and ECOG performance status. Patients with scores of 0 (n = 54), 1-2 (n = 170), and 3-6 (n = 78) according to the model were classified as low-, intermediate-, and high-risk, respectively. The corresponding median OS values were 141, 55, and 28 months, respectively. The percentage of major complications increased as tumor size increased (4-21%). Asymptomatic, nodular HCC patients with a tumor size of 5-7 cm and ALBI grade 1 benefited the most from TACE. By contrast, the value of TACE in the treatment of single huge HCC (>10 cm) with high complication rates remains unclear.

Purpose: To understand the association between biomarkers and exacerbations of severe asthma in adult patients in Taiwan., Materials and Methods: Demographic, clinical characteristics and biomarkers were retrospectively collected from the medical charts of severe asthma patients in six hospitals in Taiwan. Exacerbations were defined as those requiring asthma-specific emergency department visits/hospitalizations, or systemic steroids. Enrolled patients were divided into: (1) those with no exacerbations (non-exacerbators) and (2) those with one or more exacerbations (exacerbators). Receiver operating characteristic curves were used to determine the optimal cut-off value for biomarkers. Generalized linear models evaluated the association between exacerbation and biomarkers., Results: 132 patients were enrolled in the study with 80 non-exacerbators and 52 exacerbators. There was no significant difference in demographic and clinical characteristics between the two groups. Exacerbators had significantly higher eosinophils (EOS) counts (367.8 ± 357.18 vs. 210.05 ± 175.24, p = 0.0043) compared to non-exacerbators. The optimal cut-off values were 292 for EOS counts and 19 for the Fractional exhaled Nitric Oxide (FeNO) measure. Patients with an EOS count ≥ 300 (RR = 1.88; 95% CI, 1.26-2.81; p = 0.002) or FeNO measure ≥ 20 (RR = 2.10; 95% CI, 1.05-4.18; p = 0.0356) had a significantly higher risk of exacerbation. Moreover, patients with both an EOS count ≥ 300 and FeNO measure ≥ 20 had a significantly higher risk of exacerbation than those with lower EOS count or lower FeNO measure (RR = 2.16; 95% CI, 1.47-3.18; p = < 0.0001)., Conclusions: Higher EOS counts and FeNO measures were associated with increased risk of exacerbation. These biomarkers may help physicians identify patients at risk of exacerbations and personalize treatment for asthma patients.