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Abstract Background Dual bronchodilator therapy, consisting of a long-acting beta-agonist (LABA) and a long-acting muscarinic antagonist (LAMA), has proven effective for patients with chronic obstructive pulmonary disease (COPD). However, it remains uncertain whether there are efficacy differences between current and former smokers with COPD. This study aims to explore the effectiveness of LABA/LAMA therapies in both these groups. Methods The TOReTO trial assessed lung function, symptoms, health status, the occurrence of exacerbations, clinically significant exacerbations, and the use of LABA/LAMA therapies. These therapies include Tio/Olo, umeclidinium/vilanterol (Umec/Vi), and umeclidinium/vilanterol (Umec/Vi) are used in patients with COPD. The study examined the differences in outcomes between current and former smokers. To balance the baseline characteristics, propensity score matching (PSM) was employed. Results Data from 967 patients were collected. After PSM, the time to the first acute exacerbation in current smokers was analyzed separately for the three treatment groups and was significantly different between them (p = 0.0457). Among, there are differences in the occurrence of acute exacerbation between treatment and smoking status in Umec/Vi (p = 0.0114). There is no significant difference in the treatment of former smokers among the three different groups of LABA/LAMA fixed-dose combinations (p = 0.3079). COPD-related symptoms remained stable throughout the treatment period. There were no significant differences in symptom scores, including CAT and mMRC, among the three groups at the end of the study. Conclusions The three fixed-dose combinations of LABA/LAMA showed no difference in reducing exacerbations in former smokers but did show differences in current smokers. This trend has clinical significance, and future research will be conducted to control influencing variables to validate this point. However, due to the non-randomized study design, these findings should be interpreted with caution.

Abstract Background Myasthenia gravis (MG) is the most common paraneoplastic disorder associated with thymic neoplasms. MG can develop after thymectomy, and this condition is referred to post-thymectomy myasthenia gravis (PTMG). Diffuse panbronchiolitis (DPB), is a rare form of bronchiolitis and is largely restricted to East Asia, has been reported in association with thymic neoplasms. Only three cases of combined MG and DPB have been reported in the literature. Case presentation A 45-year-old Taiwanese woman presented to our hospital with productive cough, rhinorrhea, anosmia, ear fullness, shortness of breath, and weight loss. She had a history of thymoma, and she underwent thymectomy with adjuvant radiotherapy 7 years ago. Chest computed tomography scan revealed diffuse bronchitis and bronchiolitis. DPB was confirmed after video-assisted thoracoscopic surgery lung biopsy, and repeated sputum cultures grew Pseudomonas aeruginosa. She has been on long-term oral azithromycin therapy thereafter. Intravenous antipseudomonal antibiotics, inhaled amikacin, as well as oral levofloxacin were administered. Three months after DPB diagnosis, she developed ptosis, muscle weakness, and hypercapnia requiring the use of noninvasive positive pressure ventilation. MG was diagnosed based on the acetylcholine receptor antibody and repetitive stimulation test results. Her muscle weakness gradually improved after pyridostigmine and corticosteroid therapies. Oral corticosteroids could be tapered off ten months after the diagnosis of MG. She is currently maintained on azithromycin, pyridostigmine, and inhaled amikacin therapies, with intravenous antibiotics administered occasionally during hospitalizations for respiratory infections. Conclusions To our knowledge, this might be the first case report of sequential development of DPB followed by PTMG. The coexistence of these two disorders poses a therapeutic challenge for balancing infection control for DPB and immunosuppressant therapies for MG.

Abstract This study entailed a comprehensive GC‒MS analysis conducted on 121 patient samples to generate a clinical breathomics dataset. Breath molecules, indicative of diverse conditions such as psychological and pathological states and the microbiome, were of particular interest due to their non-invasive nature. The highlighted noninvasive approach for detecting these breath molecules significantly enhances diagnostic and monitoring capacities. This dataset cataloged volatile organic compounds (VOCs) from the breath of individuals with asthma, bronchiectasis, and chronic obstructive pulmonary disease. Uniform and consistent sample collection protocols were strictly adhered to during the accumulation of this extensive dataset, ensuring its reliability. It encapsulates extensive human clinical breath molecule data pertinent to three specific diseases. This consequential clinical breathomics dataset is a crucial resource for researchers and clinicians in identifying and exploring important compounds within the patient’s breath, thereby augmenting future diagnostic and therapeutic initiatives.

Objectives: The impact of hypoalbuminemia on the short-term and long-term mortality of cirrhotic patients with spontaneous bacterial peritonitis (SBP), both with and without renal function impairment, remains insufficiently elucidated based on population-based data. Materials and Methods: We retrieved data from Taiwan's National Health Insurance Database encompassing 14,583 hospitalized patients diagnosed with both cirrhosis and SBP during the period from January 1, 2010, to December 31, 2013. Prognostic factors influencing 30-day and 3-year survival were computed. Furthermore, the impact of hypoalbuminemia on the mortality rate among SBP patients, with or without concurrent renal function impairment, was also assessed. Results: The 30-day mortality rates for patients with SBP, comparing those with hypoalbuminemia and those without, were 18.3% and 29.4%, respectively (P < 0.001). Similarly, the 3-year mortality rates for SBP patients with hypoalbuminemia and those without were 73.7% and 85.8%, respectively (P < 0.001). Cox proportional hazard regression analysis, adjusted for patients' gender, age, and comorbid conditions, substantiated that individuals with hypoalbuminemia exhibit an inferior 30-day survival (hazard ratio [HR]: 1.62, 95% confidence interval [CI]: 1.51–1.74, P < 0.001) and reduced 3-year survival (HR: 1.57, 95% CI: 1.50–1.63, P < 0.001) in comparison to those lacking hypoalbuminemia. Among SBP patients with renal function impairment, those presenting hypoalbuminemia also experienced diminished 30-day survival (HR: 1.81, 95% CI 1.57–2.07, P < 0.001) as well as reduced 3-year survival (HR: 1.70, 95% CI 1.54–1.87, P < 0.001). Likewise, in SBP patients without renal function impairment, the presence of hypoalbuminemia was associated with poorer 30-day survival (HR: 1.54, 95% CI 1.42–1.67, P < 0.001) and 3-year survival (HR: 1.53, 95% CI 1.46–1.60, P < 0.001). Conclusion: Among cirrhotic patients with SBP, the presence of hypoalbuminemia predicts inferior short-term and long-term outcomes, regardless of renal function.

Background: Idiopathic pulmonary fibrosis (IPF) is a serious, progressive lung disease for which treatments are scarce. Pirfenidone has been approved for the treatment of IPF in Taiwan since 2016. This study aimed to gain a better insight into pirfenidone’s real-world safety and effectiveness in adult IPF patients in Taiwan. Methods: We conducted a prospective, multicenter, post-marketing surveillance study, and analyzed data from a small sample of 50 IPF patients treated with pirfenidone. Results: Most patients were men, with a mean age of 72.8 years (±10.3). They were in physiology stage I or II with a baseline mean forced vital capacity (FVC) of 2.236 L (73.8% of predicted value). After treatment with pirfenidone, the mean FVC decreased by 0.088 L at week 24 and 0.127 L at week 52. The mean 6 min walk test was 325.5 m at baseline, increased by 8.1 m at week 24, but then decreased by 23.0 m at week 52. These changes from baseline did not reach statistical significance. Pirfenidone prevented worsening of cough but did not stabilize dyspnea. During 52 weeks of treatment, the incidence of total adverse drug reactions was 62.0%, with decreased appetite (32.0%) and pruritis (10.0%) being the most common. The adverse events leading to treatment discontinuation were decreased appetite (8.0%), nausea (4.0%), and respiratory failure (4.0%). No safety concern was raised by the study. Treatment with pirfenidone stabilized both FVC and the subjective symptom of cough in most patients. Conclusions: This post-marketing surveillance study demonstrated that pirfenidone is an effective, safe, and well-tolerated treatment in patients with IPF in Taiwan.

Background: Tocilizumab has demonstrated optimal efficacy and safety in patients with rheumatoid arthritis (RA) from clinical trials. However, the risk of hepatitis B virus reactivation (HBVr) in these patients remains uncertain because patients with underlying HBV have been excluded in phase III studies. Methods: Systematical reviews were conducted on PubMed, Embase, and the Cochrane Central Register of Controlled Trials up to 21 February 2023. Random-effects meta-analysis was performed to calculate the pooled incidence of HBV reactivation. Results: We included 0 clinical trials and 11 observational studies with a total of 25 HBsAg+ and 322 HBsAg−/anti-HBc+ RA patients. Among the HBsAg+ patients without antiviral prophylaxis, the pooled rate was 69.4% (95% CI, 32.9–91.3), with a median time of 4 months (range, 1–8 months) from tocilizumab initiated. Half of these patients with HBVr experienced hepatitis flare-up but no deaths. HBVr was eliminated with prophylaxis in this population. Among HBsAg−/anti-HBc+ patients, the pooled incidence of reactivation was 3.3% (95% CI, 1.6–6.7), with a median time of 10 months (range, 2–43 months) from tocilizumab initiated. HBVr was not associated with hepatitis flare-up and death. HBsAg−/anti-HBc+ patients without anti-HBs antibodies had a significantly higher risk of HBVr (Odds ratio, 12.20; 95% CI, 1.16–128.06). Conclusions: This systematic review indicated that the risk of HBVr in RA patients with anti-HBs−, HBsAg+, or HBsAg−/anti-HBc+ cannot be ignored but may be avoided. Clinicians should consider implementing appropriate antiviral prophylaxis and monitoring policies for RA patients to avoid unnecessary hepatic side effects from tocilizumab treatment.

Eosinophilic Granulomatosis with Polyangiitis (EGPA), formerly known as Churg-Strauss syndrome, is a rare systemic vasculitis characterized by asthma, eosinophilia, and vasculitic organ involvement. This rare disease poses diagnostic challenges within the domain of severe asthma. Recognizing EGPA within the asthmatic cohort is therefore crucial for appropriate management and improved patient outcomes. Moreover, effective collaboration between rheumatologists and respiratory physicians is vital for the comprehensive care of EGPA patients. This scientific lecture aims to discuss the identification of EGPA in individuals with asthma and highlight the importance of co-care between rheumatology and respiratory medicine. This lecture will begin by providing an overview of EGPA, its clinical manifestations, and the challenges associated with differentiating it from severe asthma. The crucial identification of distinctive clinical features, such as refractory asthma, peripheral eosinophilia, and systemic symptoms, which serve as beacons for the presence of EGPA, will be discussed. Diagnostic tools encompassing imaging, laboratory tests, and biopsy techniques are explored, focusing on their utility in distinguishing EGPA from asthma. Concomitantly, the lecture will then shift its focus to the collaborative efforts required from rheumatologists and respiratory physicians in managing EGPA patients. The complementary roles of both specialties in achieving optimal patient outcomes will be discussed. Rheumatologists play a crucial role in the diagnosis and treatment of systemic vasculitis, including EGPA, while respiratory physicians provide expertise in managing asthma and respiratory complications. The case will highlight the importance of open communication, shared decision-making, and coordinated treatment plans to ensure comprehensive care for EGPA patients, addressing both their rheumatologic and respiratory needs. Real-life case will be shared to illustrate successful co-management models between rheumatology and respiratory medicine. These examples will underscore the benefits of a multidisciplinary approach, including improved disease management, reduced treatment-related complications, and enhanced patient satisfaction. In conclusion, identifying EGPA within the asthma population is crucial for appropriate management, and effective collaboration between rheumatology and respiratory physicians is essential for comprehensive care. This scientific lecture aims to provide insights into spotting EGPA among asthma patients and emphasize the significance of co-care between these specialties, ultimately improving patient outcomes and quality of life.

Abstract This is a case report of a 53‐year‐old woman who presented to our hospital in 2011 with an intermittent cough and dyspnea for 5 years. The chest X‐ray showed a prominent left hilum and a smaller right lung. Computed tomography (CT) of the chest confirmed the absence of the right pulmonary artery (PA) and the right cardiac catheterization showed a mean PA pressure of 34 mmHg. Concomitant asthma and unilateral absence of pulmonary artery (UAPA) were diagnosed. In the following years, her functional class remained stable under medications including low‐dose sildenafil and spironolactone. In 2020, she developed mild intermittent chest tightness and the coronary angiography showed a fistula between the proximal left circumflex coronary artery and right pulmonary circulation. She declined further intervention for her coronary‐pulmonary artery fistula (CPAF) and her symptoms improved spontaneously. To our knowledge, only 16 similar cases with combined UAPA and CPAF in adults have been reported in the literature, of which, pulmonary hypertension was documented in nine patients (56.3%).

Abstract Background Heterogeneity in acute respiratory distress syndrome (ARDS) has led to many statistically negative clinical trials. Etiology is considered an important source of pathogenesis heterogeneity in ARDS but previous studies have usually adopted a dichotomous classification, such as pulmonary versus extrapulmonary ARDS, to evaluate it. Etiology-associated heterogeneity in ARDS remains poorly described. Methods In this retrospective cohort study, we described etiology-associated heterogeneity in gas exchange abnormality (PaO2/FiO2 [P/F] and ventilatory ratios), hemodynamic instability, non-pulmonary organ dysfunction as measured by the Sequential Organ Failure Assessment (SOFA) score, biomarkers of inflammation and coagulation, and 30-day mortality. Linear regression was used to model the trajectory of P/F ratios over time. Wilcoxon rank-sum tests, Kruskal–Wallis rank tests and Chi-squared tests were used to compare between-etiology differences. Results From 1725 mechanically ventilated patients in the ICU, we identified 258 (15%) with ARDS. Pneumonia (48.4%) and non-pulmonary sepsis (11.6%) were the two leading causes of ARDS. Compared with pneumonia associated ARDS, extra-pulmonary sepsis associated ARDS had a greater P/F ratio recovery rate (difference = 13 mmHg/day, p = 0.01), more shock (48% versus 73%, p = 0.01), higher non-pulmonary SOFA scores (6 versus 9 points, p

Background: Data on the efficacy and safety of balloon pulmonary angioplasty (BPA) in Taiwanese patients with chronic thromboembolic pulmonary hypertension (CTEPH) are lacking. In this study, we evaluated the effects of BPA on clinical parameters including hemodynamics, echocardiography and functional status in patients with inoperable CTEPH in Taiwan. Methods: We retrospectively collected the clinical data of inoperable CTEPH patients who underwent ≥3 BPA sessions. Pulmonary hemodynamic parameters of right heart catheterization, echocardiography, 6-min walk distance and World Health Organization (WHO) functional class were collected and analyzed before and after BPA treatment. Results: A total of 59 BPA sessions were performed in 13 inoperable CTEPH patients. No periprocedural deaths or major complications requiring tracheal intubation with mechanical ventilation occurred. WHO functional class significantly improved in all 13 patients (P

Abstract Background Thrombocytopenia can rapidly improve in chronic hepatitis C (CHC) patients receiving direct-acting antiviral agents (DAA). The role of baseline (BL) thrombopoietin (TPO) in this phenomenon is unclear. Methods From June 2016 to February 2019, a total of 104 CHC patients receiving DAA, with a sustained virologic response and BL thrombocytopenia, at Dalin Tzu Chi Hospital, were enrolled in this retrospective study. Significant platelet count improvement and platelet count improvement ratio were analyzed for correlation with BL TPO. Results This cohort included 40 men (38.5%). Seventy-two (69.2%) patients had advanced fibrosis. The platelet count [median (range)] increased from 110.5 (32–149) × 103/µL at BL to 116.5 (40–196) and 118.0 (35–275) × 103/µL at end of treatment (EOT) and 12 weeks after EOT (P12), respectively, (EOT vs. BL, P

Abstract Eosinophilic granulomatosis with polyangiitis (EGPA) is a systemic vasculitis of small‐to‐medium‐sized vessels. Both eosinophilic infiltration and vasculitis are thought to contribute to multi‐organ damage. Some biologics have been used to reduce the required dose of corticosteroids in EGPA, but no single agent can ensure a complete control of this disease. Here, we describe a patient with anti‐neutrophil cytoplasmic antibodies‐negative relapsing EGPA whose asthma control was improved by omalizumab, but she continued to develop flares of abdominal and cutaneous vasculitis symptoms. After switching to mepolizumab therapy, her blood hypereosinophilia and extra‐pulmonary symptoms were significantly improved. Moreover, the dose of daily maintenance corticosteroid could be tapered off. The experience from our case suggests that biologics targeting interleukin‐5 may be more effective than omalizumab in the management of extra‐thoracic manifestations in EGPA.

Pulmonary arterial hypertension (PAH) is characterized as a progressive and sustained increase in pulmonary vascular resistance, which may induce right ventricular failure. In 2014, the Working Group on Pulmonary Hypertension of the Taiwan Society of Cardiology (TSOC) conducted a review of data and developed a guideline for the management of PAH.4 In recent years, several advancements in diagnosis and treatment of PAH has occurred. Therefore, the Working Group on Pulmonary Hypertension of TSOC decided to come up with a focused update that addresses clinically important advances in PAH diagnosis and treatment. This 2018 focused update deals with: (1) the role of echocardiography in PAH; (2) new diagnostic algorithm for the evaluation of PAH; (3) comprehensive prognostic evaluation and risk assessment; (4) treatment goals and follow-up strategy; (5) updated PAH targeted therapy; (6) combination therapy and goal-orientated therapy; (7) updated treatment for PAH associated with congenital heart disease; (8) updated treatment for PAH associated with connective tissue disease; and (9) updated treatment for chronic thromboembolic pulmonary hypertension. Keywords: Guideline, Pulmonary arterial hypertension, Pulmonary hypertension

Abstract Electronic (e)‐cigarette or vaping product use‐associated lung injury (EVALI) is a novel and potentially lethal disease first reported in the United States. We report the case of a 56‐year‐old man who presented to our hospital with dyspnoea and cough lasting for 2 months after using an e‐cigarette for approximately 50 puffs over 2 weeks. Physical examination revealed crackles in the left lower lung. High‐resolution computed tomography (HRCT) showed consolidation and ground‐glass opacities in both lungs. The baseline forced vital capacity (FVC) and diffusion capacity for carbon monoxide (DLCO) were 65.7% and 63.9% of the predicted, respectively. Lung biopsy revealed organizing pneumonia with focal fibrosis. In addition to prednisolone, he was treated with a low‐dose pirfenidone (200 mg three times per day) due to the persistence of a mild cough, exertional dyspnoea and basal crackles after discharge. His symptoms and FVC significantly improved, but the recovery of the DLCO was slow. The follow‐up HRCT demonstrated only minimal fibrotic changes. To our knowledge, this was the first reported case of EVALI successfully treated with a combination of corticosteroid and antifibrotic agents.

Hepatitis B and C (HBV/HCV) coinfected patients have a potential risk of hepatitis B reactivation (HBVr) after direct-acting antivirals (DAAs) treatment. The study intends to investigate the predictive role of HBV biomarkers in HBVr. Forty-six HBV/HCV coinfected patients receiving DAAs were enrolled. All patients completed treatment and follow-up to the 12th-week post-DAA treatment (P12). Blood samples were measured for HBV biomarkers, including hepatitis B surface antigen (HBsAg), hepatitis B core-related antigen (HBcrAg), and HBV pregenomic RNA (HBV pgRNA). The predictive factors for HBVr after DAA treatment were analyzed. Among 31 patients without nucleot(s)ide analogue (NA) treatment, seven (22.5%, 7/31) developed HBVr without hepatitis flare-up. Patients with HBVr had higher HBsAg titers than those without HBVr from baseline to P12 (p = 0.008, 0.009, 0.004, and 0.006 at baseline, week 4, end of treatment, and P12, respectively). The baseline HBsAg level was the only predictive factor associated with HBVr (HR, 2.303; 95% CI, 1.086–4.882; p = 0.030). In predicting HBVr, a baseline HBsAg titer > 20 IU/mL had a sensitivity, specificity, positive predictive value, and negative predictive value of 85.7%, 75.0%, 50%, and 94.7%, respectively. No patient had HBVr if the baseline HBsAg titer was

BackgroundChanges in renal function in chronic hepatitis C (CHC) patients receiving direct-acting antivirals (DAAs) are controversial. The evolution of neutrophil gelatinase-associated lipocalin (NGAL) in these patients remains unclear.MethodsA total of 232 CHC patients receiving DAA at Dalin Tzu Chi Hospital from May 2016 to February 2019, were enrolled in this retrospective study. Grade 2/3 renal function deterioration, defined as a decrease in eGFR between 10% and 50% from baseline (BL) to 12 weeks after the end of treatment (P12), was investigated for its association with BL characteristics. The changes in renal function and NGAL levels were also analyzed at the SOF-base or nonSOF-base DAA.ResultsSixty-two patients (26.7%) had grade 2/3 renal function deterioration at P12 after DAA therapy. Univariate analysis showed that it was associated with age (P = 0.038). Multivariate analysis indicated that age (OR = 1.033, 95% CI: 1.004-1.064, P = 0.027), sex (male; OR = 2.039, 95% CI: 1.093-3.804, P = 0.025), ACEI/ARB use (OR = 2.493, 95% CI: 1.016-6.119, P = 0.046), and BL NGAL (OR = 1.033, 95% CI: 1.001-1.067, P = 0.046) positively correlated with grade 2/3 renal function deterioration. Furthermore, eGFR was decreased (P = 0.009) and NGAL was increased (P = 0.004) from BL to P12 in CHC patients receiving SOF-based DAA.ConclusionsOf the CHC patients receiving DAA therapy, 26.7% had grade 2/3 renal function deterioration at P12, and it was associated with older age, gender being male, ACEI/ARB use, and higher BL NGAL levels. In addition, NGAL might be a biomarker of nephrotoxicity at P12 in patients receiving SOF-based DAA.

Pulmonary hypertension (PH) is a fatal disease—even with state-of-the-art medical treatment. Non-invasive clinical tools for risk stratification are still lacking. The aim of this study was to investigate the clinical utility of heart rhythm complexity in risk stratification for PH patients. We prospectively enrolled 54 PH patients, including 20 high-risk patients (group A; defined as WHO functional class IV or class III with severely compromised hemodynamics), and 34 low-risk patients (group B). Both linear and non-linear heart rate variability (HRV) variables, including detrended fluctuation analysis (DFA) and multiscale entropy (MSE), were analyzed. In linear and non-linear HRV analysis, low frequency and high frequency ratio, DFAα1, MSE slope 5, scale 5, and area 6–20 were significantly lower in group A. Among all HRV variables, MSE scale 5 (AUC: 0.758) had the best predictive power to discriminate the two groups. In multivariable analysis, MSE scale 5 (p = 0.010) was the only significantly predictor of severe PH in all HRV variables. In conclusion, the patients with severe PH had worse heart rhythm complexity. MSE parameters, especially scale 5, can help to identify high-risk PH patients.

Abstract Studies about prognostic assessment in cancer patients requiring prolonged mechanical ventilation (PMV) for post-intensive care are scarce. We retrospectively enrolled 112 cancer patients requiring PMV support who were admitted to the respiratory care center (RCC), a specialized post-intensive care weaning facility, from November 2009 through September 2013. The weaning success rate was 44.6%, and mortality rates at hospital discharge and after 1 year were 43.8% and 76.9%, respectively. Multivariate logistic regression showed that weaning failure, in addition to underlying cancer status, was significantly associated with an increased 1-year mortality (odds ratio, 6.269; 95% confidence interval, 1.800–21.834; P = 0.004). Patients who had controlled non-hematologic cancers and successful weaning had the longest median survival, while those with other cancers who failed weaning had the worst. Patients with low maximal inspiratory pressure, anemia, and poor oxygenation at RCC admission had an increased risk of weaning failure. In conclusion, cancer status and weaning outcome were the most important determinants associated with long-term mortality in cancer patients requiring PMV. We suggest palliative care for those patients with clinical features associated with worse outcomes. It is unknown whether survival in this specific patient population could be improved by modifying the risk of weaning failure.

Background: Plasma calcitonin gene-related peptide (CGRP) plays a key role in the migraine pathophysiology. This study aimed to investigate its role in predicting diagnosis and outcome of pharmacotherapy in pediatric migraine.Methods: We prospectively recruited 120 subjects, who never took migraine-preventive agents in a pediatric clinic, including 68 patients with migraine, 30 with non-migraine headache (NM), and 22 non-headache (NH) age-matched controls. Short-term therapeutic response was measured for at least 2 weeks after the start of therapy. Responders were defined with >50% headache reduction. Plasma CGRP concentrations were measured by ELISA.Results: In the migraine group, more patients required acute therapy, as compared to the NM group (62/68, 91% vs. 5/30, 15%, p = 0.001). The mean plasma CGRP level in migraineurs either during (291 ± 60 pg/ml) or between (240 ± 48) attacks was higher than in NM patients (51 ± 5 pg/ml, p = 0.006 and 0.018, respectively) and NH controls (53 ± 6 pg/ml, p = 0.016 and 0.045, respectively). Forty-seven patients (69%) needed preventive treatments and had higher plasma CGRP levels (364 ± 62 pg/ml, n = 47) than those not (183 ± 54 pg/ml, n = 21) (p = 0.031). Topiramate responders had higher plasma CGRP levels than non-responders (437 ± 131 pg/ml, n = 14 vs. 67 ± 19 pg/ml, n = 6, p = 0.021). Survival curves of plasma CGRP levels also showed those with higher CGRP levels responded better to topiramate. Differences were not found in the other preventives.Conclusion: The plasma CGRP level can differentiate migraine from non-migraine headache. It may also serve as a reference for the therapeutic strategy since it is higher in patients requiring migraine prevention and responsive to short-term topiramate treatment. These results are clinically significant, especially for the young children who cannot clearly describe their headache symptoms and may provide new insights into the clinical practice for the diagnosis and treatment of pediatric migraine.

Background: Valproic acid (VPA) and topiramate (TPM), initially developed as antiepileptics, are approved for migraine prophylaxis in adults but not children. The differences in their antimigraine mechanism(s) by age remain unclear.Methods: A migraine model induced by intra-cisternal (i.c.) capsaicin instillation in pediatric (4–5 weeks) and adult (8–9 weeks) rats was pretreated with VPA (30, 100 mg/kg) or TPM (10, 30, 100 mg/kg). Noxious meningeal stimulation by the irritant capsaicin triggered trigeminovascular system (TGVS) activation mimicking migraine condition, which were assessed peripherally by the depletion of calcitonin gene-related peptide (CGRP) in sensory nerve fibers of the dura mater, the increased CGRP immunoreactivity at trigeminal ganglia (TG) and centrally by the number of c-Fos-immunoreactive (c-Fos-ir) neurons in the trigeminocervical complex (TCC). Peripherally, CGRP released from dural sensory nerve terminals of TG triggered pain signal transmission in the primary afferent of trigeminal nerve, which in turn caused central sensitization of the TGVS due to TCC activation and hence contributed to migraine.Results: In the VPA-treated group, the central responsiveness expressed by reducing the number of c-Fos-ir neurons, which had been increased by i.c. capsaicin, was significant in pediatric, but not adult, rats. Inversely, VPA was effective in peripheral inhibition of elevated CGRP immunoreactivity in the TG and CGRP depletion in the dura mater of adult, but not pediatric, rats. In TPM group, the central responsiveness was significant in both adult and pediatric groups. Peripherally, TPM significantly inhibited capsaicin-induced CGRP expression of TG in adult, but not pediatric, rats. Interestingly, the capsaicin-induced depletion of CGRP in dura was significantly rescued by TPM at high doses in adults, but at low dose in pediatric group.Conclusion: These results suggest VPA exerted peripheral inhibition in adult, but central suppression in pediatric migraine-rats. In contrast, TPM involves both central and peripheral inhibition of migraine with an optimal therapeutic window in both ages. These findings may clarify the age-dependent anti-migraine mechanism of VPA and TPM, which may guide the development of new pediatric anti-migraine drugs in the future.

Hepatic hydrothorax is an uncommon but important complication of liver cirrhosis. The optimal management of this condition remains unclear. This retrospective study evaluated the impact of therapeutic interventions on the outcome of patients with hepatic hydrothorax. Methods: From August 1996 to March 2004, the medical charts of 52 patients with hepatic hydrothorax in the National Taiwan University Hospital were reviewed. Treatment methods, outcome of interventions, and survival time were described and analyzed. Results: At the time of diagnosis, four patients were Child-Pugh class A, 20 were class B, and 28 were class C. Twenty-eight (53.8%) patients received supportive care with thoracentesis for symptom relief. Among the other 24 patients, 16 (30.8%) were treated by chemical pleurodesis, 14 (26.9%) underwent surgical interventions, and six (11.5%) received both interventions. Intervention success, defined as resolution of hydrothorax for at least 3 months after the procedure, was achieved in 37.5% and 42.9% of patients who underwent chemical pleurodesis and surgery, respectively, with an overall success rate of 50%. The median survival of all patients was 8.6 months (range, 0.2–77.6 months). The median survival of patients with intervention success (22.5 months) was significantly longer than those with intervention failure (5.4 months) and supportive care (6.3 months). Multivariate analysis showed that only intervention success (p = 0.010, hazard ratio =0.25) was an independent predictor of survival. Conclusion: For patients with hepatic hydrothorax, aggressive medical or surgical intervention might improve survival over supportive management, especially when resolution of hydrothorax can be maintained for at least 3 months.

The rapid shallow breathing index (RSBI) is a weaning parameter usually measured at the start of a spontaneous breathing trial (SBT). This study investigated the value of RSBI measured at the beginning and termination of SBT as a predictor of weaning outcome. Methods: RSBI was measured during the initial 1 minute (RSBI1) and at termination (RSBI2) of an SBT in 172 patients recovering from acute respiratory failure. Results: Weaning was successful in 106 patients and failed in 66 patients. Among the 66 patients with weaning failure, 12 required reintubation within 48 hours (extubation failure), and the remaining 54 patients could not be extubated after SBT (trial failure). There were no differences between RSBI1 in the three groups (69.4 ± 27.5, 81.7 ± 24.4 and 75.5 ± 26.5, respectively), but RSBI2 was significantly higher in patients with extubation failure (95.9 ± 20.6) and trial failure (98.0 ± 50.0) than in patients with weaning success (64.6 ± 26.3) (both p < 0.001). Logistic regression revealed that RSBI2 was superior to RSBI1 and various physiologic indices in predicting weaning outcome. For the 118 extubated patients, the mean area under the receiver operating characteristic curve for RSBI2 and RSBI1 was 0.83 and 0.63, respectively. Using a threshold value of 105, the sensitivity, specificity, accuracy and likelihood ratio for weaning outcome were 0.91, 0.25, 0.85 and 1.38 for RSBI2 and 0.89, 0.16, 0.60 and 1.06 for RSBI1, respectively. Conclusion: This study found that RSBI measured at the completion of SBT was superior to that measured at the start in predicting weaning outcome in critically ill patients.

Several studies on diagnostic accuracy of pleural N-terminal pro-B-type natriuretic peptide (NT-pro-BNP) for effusions from congestive heart failure (CHF) conclude that pleural NT-pro-BNP is a useful biomarker with high diagnostic accuracy for distinguishing CHF effusions. However, its applicability in critical care settings remains uncertain and requires further investigations.NT-proBNP was measured in pleural fluid samples of a prospective cohort of intensive care unit patients with pleural effusions. Receiver operating characteristic curve analysis was performed to determine diagnostic accuracy of pleural NT-proBNP for prediction of CHF effusions.One hundred forty-seven critically ill patients were evaluated, 38 (26%) with CHF effusions and 109 (74%) with non-CHF effusions of various causes. Pleural NT-proBNP levels were significantly elevated in patients with CHF effusions. Pleural NT-pro-BNP demonstrated the area under the curve of 0.87 for diagnosing effusions due to CHF. With a cutoff of 2200 pg/mL, pleural NT-proBNP displayed high sensitivity (89%) but moderate specificity (73%). Notably, 29 (27%) of 109 patients with non-CHF effusions had pleural NT-proBNP levels >2200 pg/mL and these patients were more likely to experience septic shock (18/29 vs. 10/80, P

Objective: We present an unusual case of maternal death following medical treatment of paroxysmal supraventricular tachycardia (PSVT) in late gestation. Case Report: A 30-year-old woman, gravida 1, para 0, came to the outpatient clinic of our obstetrics and gynecology department at 35 weeks of gestation. She had suffered from palpitation and shortness of breath that lasted 3 days. Electrocardiographic examination revealed PSVT. Although intravenous administration of verapamil (5 mg) and adenosine (36 mg) effectively prevented the relapse of PSVT, the patient lost consciousness 30 minutes after her last dose of adenosine with sudden-onset convulsions. Despite immediate administration of advanced cardiac life support, she showed no signs of improvement and died. Conclusion: PSVT in late gestation can be associated with maternal death even following conversion to sinus rhythm using medical treatment. Clinical use of adenosine for PSVT should alert the clinician to the potential risk of administering a high dose of adenosine to a pregnant woman, which can lead to maternal mortality in late gestation. Administration of a high dose of adenosine was, in our opinion, partially responsible for the maternal death and intrauterine fetal demise in this case.

INTRODUCTION: The effect of hemoglobin levels on the weaning outcomes of mechanically ventilated patients remains under debate, particularly for the patients with difficult weaning. This study aims to evaluate the effect of hemoglobin levels on weaning outcomes in difficult-to-wean patients. METHODS: This retrospective cohort study was conducted in a university-affiliated teaching hospital in Taiwan. Patients who fulfilled the criteria of difficult weaning were enrolled. Medical records were reviewed to obtain data on hemograms, biochemistry tests, transfusion records, comorbidities and weaning outcome. The association between hemoglobin levels and 30-day weaning outcomes was evaluated using a logistic regression model. RESULTS: A total of 751 patients received mechanical ventilation during the study period, 138 of whom fulfilled the criteria of difficult weaning. Compared with the patients whose hemoglobin was 10 g/dL). Multivariate analysis showed that the odds ratio for weaning success remained significant for hemoglobin levels of 8-10 g/dL (adjusted OR, 3.3; 95% CI, 1.07-10.15) with borderline significance for hemoglobin level > 10 g/dL (adjusted OR, 2.95, 95% CI, 0.88-9.96). CONCLUSIONS: Hemoglobin level is independently associated with weaning outcome in difficult-to-wean patients. Further studies are needed to evaluate whether a restrictive transfusion trigger for acute critical illness is also appropriate for such patients.

Background: Benralizumab is indicated as add-on therapy in patients with uncontrolled, severe eosinophilic asthma; it has not yet been evaluated in a large Asian population with asthma in a clinical trial., Objective: To evaluate the efficacy and safety of benralizumab in patients with severe asthma in Asia., Methods: MIRACLE (NCT03186209) was a randomized, Phase 3 study in China, South Korea, and the Philippines. Patients aged 12-75 years with severe asthma receiving medium-to-high-dose inhaled corticosteroid/long-acting β 2 -agonists, stratified (2:1) by baseline blood eosinophil count (bEOS) (≥300/μL; <300/μL), were randomized (1:1) to benralizumab 30 mg or placebo. Endpoints included annual asthma exacerbation rate (AAER; primary endpoint), change from baseline at Week 48 in pre-bronchodilator (BD) forced expiratory volume in 1 second (pre-BD FEV 1 ) and total asthma symptom score (TASS). Safety was evaluated ≤ Week 56., Results: Of 695 patients randomized, 473 had baseline bEOS ≥300/μL (benralizumab n = 236; placebo n = 237). In this population, benralizumab significantly reduced AAER by 74% (rate ratio 0.26 [95% CI 0.19, 0.36], p < 0.0001) and significantly improved pre-BD FEV 1 (least squares difference [LSD] 0.25 L [95% CI 0.17, 0.34], p < 0.0001) and TASS (LSD -0.25 [-0.45, -0.05], p = 0.0126) versus placebo. In patients with baseline bEOS <300/μL, there were numerical improvements in AAER, pre-BD FEV 1 , and TASS with benralizumab versus placebo. The frequency of adverse events was similar for benralizumab (76%) and placebo (80%) in the overall population., Conclusions: MIRACLE data reinforces the efficacy and safety of benralizumab for severe eosinophilic asthma in an Asian population, consistent with the global Phase 3 results., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Nanshan Zhong reports financial support was provided by AstraZeneca. Kefang Lai reports financial support was provided by AstraZeneca. Dejun Sun reports financial support was provided by AstraZeneca. Ranran Dai reports financial support was provided by AstraZeneca. Ronnie Samoro reports financial support was provided by AstraZeneca. Hae-Sim Park reports financial support was provided by AstraZeneca. Annika Astrand reports a relationship with AstraZeneca that includes: employment and equity or stocks. David Cohen reports a relationship with AstraZeneca that includes: employment and equity or stocks. Maria Jison reports a relationship with AstraZeneca that includes: employment and equity or stocks. Vivian H Shih reports a relationship with AstraZeneca that includes: employment and equity or stocks. Viktoria Werkstrom reports a relationship with AstraZeneca that includes: employment and equity or stocks. Yuhui Yao reports a relationship with AstraZeneca that includes: employment and equity or stocks. Yajuan Zhang reports a relationship with AstraZeneca that includes: employment and equity or stocks. Wenying Zheng reports a relationship with AstraZeneca that includes: employment and equity or stocks. Tanya Jandu and Helen Brereton of inScience Communications, Springer Healthcare Ltd, UK, provided medical writing support, which was funded by AstraZeneca. If there are other authors, they 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. Published by Elsevier Ltd.)