Stented cryopreserved aortic allograft for reconstruction of long-segment post-tuberculosis tracheal stenosis.

Tracheobronchial tuberculosis is one of the conditions causing long segment tracheal stenosis and is a clinically challenging scenario. This report describes a successful tracheal reconstruction in a 44-year-old man with long-segment post-tuberculosis tracheobronchial stenosis, utilizing a stented cryopreserved aortic allograft. The procedure was necessitated by the failure of conventional treatments. The stenotic segment was resected and replaced with a cryopreserved aortic allograft, supported by a metallic stent to maintain airway patency. Post-surgery, the patient experienced resolution of dyspnea without major complications. Currently, at 33 months post-operation, the patient enjoys an enhanced quality of life with effective breathing, speaking, swallowing abilities, and has resumed normal daily activities, with regular bronchoscopic follow-ups. This report demonstrates a novel approach for managing challenging tuberculosis-induced long segment airway stenosis.

Dexmedetomidine for enhanced recovery after non-intubated video-assisted thoracoscopic surgery.

BACKGROUND: Non-intubated video-assisted thoracoscopic surgery combines a minimally invasive technique with multimodal locoregional analgesia to enhance recovery. The mainstay sedation protocol involves propofol and fentanyl. Dexmedetomidine, given its opioid-sparing effect with minimal respiratory depression, facilitates sedation in non-intubated patients. This study aimed to evaluate the efficacy of dexmedetomidine during non-intubated video-assisted thoracoscopic surgery. METHODS: A total of 114 patients who underwent non-intubated video-assisted thoracoscopic surgery between June 2015 and September 2017 were retrospectively evaluated. Of these, 34 were maintained with dexmedetomidine, propofol, and fentanyl, and 80 were maintained with propofol and fentanyl. After a 1:1 propensity score-matched analysis incorporating sex, body mass index, American Society of Anesthesiologists classification, pulmonary disease and hypertension, the clinical outcomes of 34 pairs of patients were assessed. RESULTS: The dexmedetomidine group showed a significantly lower opioid consumption [10.3 (5.7-15.1) vs. 18.8 (10.0-31.0) mg, median (interquartile range); P = 0.001] on postoperative day 0 and a significantly shorter postoperative length of stay [3 (2-4) vs. 4 (3-5) days, median (interquartile range), P = 0.006] than the control group. During operation, the proportion of vasopressor administration was significantly higher in the dexmedetomidine group [18 (53) vs. 7 (21), patient number (%), P = 0.01]. On the other hand, the difference of the hypotension and bradycardia incidence, short-term morbidity and mortality rates between each group were nonsignificant. CONCLUSIONS: Adding adjuvant dexmedetomidine to propofol and fentanyl is safe and feasible for non-intubated video-assisted thoracoscopic surgery. With its opioid-sparing effect and shorter postoperative length of stay, dexmedetomidine may enhance recovery after surgery.

Discrimination of invasive lung adenocarcinoma from Lung-RADS category 2 nonsolid nodules through visual assessment: a retrospective study.

OBJECTIVES: Invasive adenocarcinomas (IADs) have been identified among nonsolid nodules (NSNs) assigned as Lung Imaging Reporting and Data System (Lung-RADS) category 2. This study used visual assessment for differentiating IADs from noninvasive lesions (NILs) in this category. METHODS: This retrospective study included 222 patients with 242 NSNs, which were resected after preoperative computed tomography (CT)-guided dye localization. Visual assessment was performed by using the lung and bone window (BW) settings to classify NSNs into BW-visible (BWV) and BW-invisible (BWI) NSNs. In addition, nodule size, shape, border, CT attenuation, and location were evaluated and correlated with histopathological results. Logistic regression was performed for multivariate analysis. A p value of < 0.05 was considered statistically significant. RESULTS: A total of 242 NSNs (mean diameter, 7.6 ± 2.8 mm), including 166 (68.6%) BWV and 76 (31.4%) BWI NSNs, were included. IADs accounted for 31% (75) of the nodules. Only 4 (5.3%) IADs were identified in the BWI group and belonged to the lepidic-predominant (n = 3) and acinar-predominant (n = 1) subtypes. In univariate analysis for differentiating IADs from NILs, the nodule size, shape, CT attenuation, and visual classification exhibited statistical significance. Nodule size and visual classification were the significant predictors for IAD in multivariate analysis with logistic regression (p < 0.05). The sensitivity, specificity, positive predictive value, and negative predictive value of visual classification in IAD prediction were 94.7%, 43.1%, 42.8%, and 94.7%, respectively. CONCLUSIONS: The window-based visual classification of NSNs is a simple and objective method to discriminate IADs from NILs. CLINICAL RELEVANCE STATEMENT: The present study shows that using the bone window to classify nonsolid nodules helps discriminate invasive adenocarcinoma from noninvasive lesions. KEY POINTS: • Evidence has shown the presence of lung adenocarcinoma in Lung-RADS category 2 nonsolid nodules. • Nonsolid nodules are classified into the bone window-visible and the bone window-invisible nonsolid nodules, and this classification differentiates invasive adenocarcinoma from noninvasive lesions. • The Lung-RADS category 2 nonsolid nodules are unlikely invasive adenocarcinoma if they show nonvisualization in the bone window.

Application of aortic allograft in trachea transplantation.

BACKGROUND: The use of tracheal implants for tracheal reconstruction remains a challenge in thoracic medicine due to the complex structure of the trachea in mammalian organisms, including smooth muscles, cartilage, mucosa, blood vessels, cilia, and other tissues, and the difficulty in achieving tracheal regeneration using implants from either allografts or synthetic biomaterials. METHODS: This project used the Lee-Sung strain pig, a swine breed local to Taiwan, as the experimental subject. The aorta of the pig was harvested, decellularized to form the scaffold, and transplanted into the trachea of allogeneic pigs together with growth factors. Postoperative physiological function and tissue changes were observed. The postoperative physiological parameters of the LSP were monitored, and they were sacrificed after a certain period to observe the pathological changes in the tracheal epithelial cells and cartilages. RESULTS: Overall, six LSP tracheal transplantations were performed between March 4, 2020, and March 10, 2021. These included aortic patch anastomosis for pig 1 and aortic segmental anastomosis for pigs 2-6. The shortest and longest survival periods were 1 day and 147 days, respectively. Excluding the pig that survived for only 1 day due to a ruptured graft anastomosis, all other subjects survived for over 1 month on average. CONCLUSION: In this study, we grafted a decellularized porcine aorta into a recipient pig with a tracheal defect. We found cryopreservation of the allogeneic aorta transplantation was a feasible and safe method for the management of airway disease, and immunosuppressants were unnecessary during the treatment course.

Uniportal versus multiportal nonintubated thoracoscopic anatomical resection for lung cancer: A propensity-matched analysis.

BACKGROUND/PURPOSE: No studies have compared between uniportal and multiportal nonintubated thoracoscopic anatomical resection for non-small cell lung cancer (NSCLC). We aimed to compare short- and long-term postoperative outcomes concerning these two methods. METHODS: Our retrospective dataset comprised patients with NSCLC who underwent uniportal or multiportal nonintubated thoracoscopic anatomical resection between January 2011 and December 2019. The primary outcome was recurrence-free survival. Propensity scores were matched according to age, sex, body mass index, pulmonary function, tumor size, cancer stage, and surgical method. RESULTS: In total, 1130 such patients underwent nonintubated video-assisted thoracoscopic surgery (VATS), and 490 consecutive patients with stage I-III NSCLC underwent nonintubated anatomical resection, including lobectomy and segmentectomy (uniportal, n = 158 [32.3%]; multiportal, n = 331 [67.7%]). The uniportal group had fewer dissected lymph nodes and lymph node stations. In paired group analysis, the uniportal group had shorter operation durations (99.8 vs. 138.2 min; P < 0.001), lower intensive care unit (ICU) admission rates and ICU admission intervals (7.0% vs. 27.8%; P < 0.001), and shorter postoperative hospital stays (4.1 days vs. 5.2 days; P < 0.001). The most common postoperative complication was prolonged air leaks. No surgical mortality was observed. The multiportal group had higher complication rates for grades ≥ II NSCLC; however, this difference was not significant (4.4% vs. 1.3%, respectively; P = 0.09). CONCLUSION: Nonintubated uniportal VATS for anatomical resection had better results for some perioperative outcomes than multiportal VATS. Oncological outcomes such as recurrence-free and overall survival remained uncompromised, despite fewer dissected lymph nodes.

Primary Tumor Resection for Stage IV Non-small-cell Lung Cancer Without Progression After First-Line Epidermal Growth Factor Receptor-Tyrosine Kinase Inhibitor Treatment: A Retrospective Case-Control Study.

BACKGROUND: In studies of stage IV epidermal growth factor receptor (EGFR)-mutant nonsmall-cell lung cancer (NSCLC), <10% of patients underwent surgery; thus, the effect of surgery in these patients remains unclear. We investigated whether primary lung tumor resection could improve the survival of patients with stage IV EGFR-mutant NSCLC without progression after first-line EGFR-tyrosine kinase inhibitor (EGFR-TKI) treatment. METHODS: This retrospective case-control study included patients treated with first-line EGFR-TKIs without progression on follow-up imaging. Patients in the surgery group (n = 56) underwent primary tumor resection, followed by TKI maintenance therapy. Patients in the control group (n = 224; matched for age, metastatic status, and Eastern Cooperative Oncology Group performance status) received only TKI maintenance therapy. Local ablative therapy for distant metastasis was allowed in both groups. The primary endpoint was progression-free survival. The secondary endpoints were overall survival, failure patterns, and complications/adverse events. RESULTS: The median time from TKI treatment to surgery was 5.1 months. For the surgery and control groups, the median follow-up periods were 34.0 and 38.5 months, respectively, with a median (95% confidence interval) progression-free survival of 29.6 (18.9-40.3) and 13.0 (11.8-14.2) months, respectively (P < 0.001). Progression occurred in 29/56 (51.8%) and 207/224 (92.4%) patients, respectively. The median overall survival in the surgery group was not reached. The rate of surgical complications of grade ≥2 was 12.5%; complications were treated conservatively. CONCLUSIONS: Primary tumor resection is feasible for patients with EGFR-mutant nonprogressed NSCLC during first-line EGFR-TKI treatment and may improve survival better than maintenance EGFR-TKI therapy alone.

Video-assisted thoracoscopic surgery for primary pulmonary cryptococcosis.

BACKGROUND: The surgical outcome for primary pulmonary cryptococcosis remains unclear. In this study, we investigated the clinical characteristics, treatment, and outcomes of video-assisted thoracoscopic surgery (VATS) for primary pulmonary cryptococcosis. METHODS: We retrospectively reviewed the medical records of 49 patients with confirmed pulmonary cryptococcosis who underwent VATS for pulmonary nodules at the National Taiwan University Hospital between May 2013 and March 2019. Serum cryptococcal antigen (CryAg)-positive and CryAg-negative patients were compared. RESULTS: The diagnosis of pulmonary cryptococcosis was confirmed using histopathology or tissue swab culture. The mean age of the patients was 56.0 ± 12.2 years, and 27 patients (55.1%) were male. Most patients were asymptomatic (67.3%) and admitted following the detection of pulmonary lesions on a computed tomography scan of the chest. A greater proportion of patients in the CryAg-positive group (62.5%) underwent lobectomy compared with those in the CryAg-negative group (7.3%, P < 0.001). Three patients (6.1%) had neurological symptoms (headache or dizziness) and all were serum CryAg-positive. One patient with Cryptococcus gattii developed fluctuating serum CryAg titers after a 12-month antifungal treatment. No relapse occurred in the remaining 48 patients, irrespective of postoperative antifungal treatment. CONCLUSION: In patients with primary pulmonary cryptococcosis, serum CryAg detection rate is low, and VATS was an effective and safe diagnostic and therapeutic tool.

Experiences with pulmonary endarterectomy for chronic thromboembolic pulmonary hypertension at multiple centers in Taiwan.

BACKGROUND: Of the types of pulmonary hypertension, chronic thromboembolic pulmonary hypertension (CTEPH) may be cured through pulmonary endarterectomy (PEA). In this study, we investigated patient experiences with PEA for CTEPH treatment in Taiwan. METHODS: We retrospectively reviewed the records of patients who underwent PEA in two medical centers between January 2005 and December 2019. We measured the following outcomes: in-hospital complications, improvements in cardiac function and exercise capacity, survival using Kaplan-Meier analysis after PEA. RESULTS: Twenty-seven patients (female: 17) with a mean age of 52.6 years underwent PEA. Pre-operatively, most patients were New York Heart Association functional class (NYHA FC) III (n = 19) and IV (n = 7). The mean periods from the onset of symptoms to diagnosis and from diagnosis to operation were 22.6 and 22.3 months, respectively. After PEA, mean intubation time, and length of intensive care unit and hospital stay were 9, 11, and 20 days, respectively. Most patients' NYHA FCs improved to I (n = 15) and II (n = 10). The mean 6-min walk test (6MWT) result improved by 60.5%. The in-hospital mortality, mean follow-up period, and 5- and 10-year overall survival rates were 3.7%, 77.0 months, 96.3%, and 84.3%, respectively. Furthermore, 5- and 10-year disease-specific survival rates were both 96.3%. CONCLUSION: When pre-operative and post-operative statuses were compared, we found a significant improvement in NYHA FC and 6MWT distance. Our study also found a lower in-hospital mortality rate compared to other published studies, except compared to the newer data provided by the University of California, San Diego group.

Comparison of perioperative outcomes between intubated and nonintubated thoracoscopic surgery in children.

BACKGROUND/PURPOSE: This study aimed to compare our experiences of nonintubated video-assisted thoracoscopic surgery (VATS) for pneumothorax and lung tumor resections with that of intubated VATS in pediatric patients. METHODS: In total, 17 nonintubated and 64 intubated pediatric VATS were performed between January 2012 and December 2018. Patient characteristics, operation period, comorbidities, precedent lung surgery, diagnosis, type of anesthesia, side and type of procedure, and perioperative outcomes were collected from medical records. Perioperative outcome data included induction time, operation time, postoperative chest tube drainage duration, and length of stay. Simple linear regression and multiple linear regression analyses were used to determine the influence of selected variables on perioperative outcomes. RESULTS: The mean age was 16.2 years in the intubated group and 15.2 years in the nonintubated group. Comorbidities including malignancy and asthma were noted in 9 intubated patients and 6 nonintubated patients. Nonintubated VATS was performed in 9 pneumothorax surgeries and 8 lung tumor resections. Five patients breathed oxygen through a face mask, 3 patients through a high-flow nasal cannula, and 9 patients through a laryngeal mask airway. No patient required tracheal intubation or thoracotomy. No major operative complications were noted in either group. After adjustments for statistically relevant confounders, the multiple regression analysis showed that the nonintubated technique influenced the length of stay, leading to a reduction of 0.75 days. CONCLUSION: Nonintubated VATS is feasible and safe in selected children undergoing bullectomy or wedge resections for lung tumors. The nonintubated approach might enhance postoperative recovery.

Mortality risk factors in patients on waiting list for lung transplantation between 2005 and 2018: A single institutional experience.

BACKGROUND: Lung transplantation is a therapeutic option for patients with end-stage lung disease. However, the increase in organ demand has surpassed the number of donors, with many patients unable to outlive the long waiting period. This study aimed to assess mortality and its risk factors in patients on the waiting list for lung transplantation in a single medical centre. METHODS: All evaluated clinical and laboratory data of the patients with end-stage lung disease assessed for lung transplantation between February 2005 and November 2018 in National Taiwan University Hospital were recorded in the waiting list database. The patients in this study were divided into two groups: survival and death groups. RESULTS: Between February 2005 and November 2018, 169 patients were enrolled in the waiting list. Thirty-one patients were alive and waiting for the chance of lung transplantation, 56 underwent lung transplantation, and 82 died while waiting. The mean age of all patients was 43.7 years, and 91 were women. The mean body mass index (BMI) was 20.3. The most common blood type was type O. All patients were in New York Heart Association (NYHA) class III or IV. After analysis of the two groups, lower BMI presented as a mortality factor. CONCLUSION: This is the first Taiwanese study to describe the mortality factors in patients waiting for lung transplantation. The main factors influencing the survival of these patients were lower BMI, NYHA class IV, and diseases which cause end-stage lung diseases (infection and pulmonary fibrosis).

Undiagnosed solitary caseating granulomas: Is lung resection surgery a feasible method for diagnosis and treatment?

BACKGROUND: In many patients, low-dose computed tomography (CT) screening for lung cancer reveals asymptomatic pulmonary nodules. Lung resection surgery may be indicated in these patients; however, distinguishing malignancies from benign lesions preoperatively can be challenging. METHODS: From 2013 to 2018, 4181 patients undergoing surgery for pulmonary nodules were reviewed at National Taiwan University Hospital, and 837 were diagnosed with benign pathologies. Only patients with pathological diagnosis as caseating granulomatous inflammation were included, sixty-nine patients were then analyzed for preoperative clinical and imaging characteristics, surgical methods and complications, pathogens, medical treatment and outcomes. Mycobacterial evidence was obtained from the culture of respiratory or surgical specimen. RESULTS: Overall, 68% of the patients were asymptomatic before surgery. More than half of the nodules were in the upper lobes, and all patients underwent video-assisted thoracoscopic surgery (VATS). Some patients (14.5%) developed grade I complications, and the mean postoperative hospital stay was 4 days. The final pathology reports of 20% benign entities postoperatively, and caseating granulomatous inflammation accounted for a significant part. MTB and NTM were cultured from one-fourth of the patients respectively. All patients with confirmed MTB infection received antimycobacterial treatment, while the medical treatment in NTM-infected patients was decided by the infectious disease specialists. The mean follow-up period was 736 days, and no recurrence was found. CONCLUSION: Lung resection surgery is an aggressive but safe and feasible method for diagnosing MTB- or NTM-associated pulmonary nodules, and, potentially, an effective therapeutic tool for patients with undiagnosed MTB- or NTM-associated pulmonary nodules.

Thoracoscopic Wedge Resection Versus Segmentectomy for cT1N0 Lung Adenocarcinoma.

BACKGROUND: The choice between wedge resection and segmentectomy as a sublobar resection method for patients with cT1N0 lung cancer remains debatable. This study aimed to evaluate the clinical outcomes after wedge resection and segmentectomy for patients with cT1N0 lung adenocarcinoma. METHODS: The study enrolled 1002 consecutive patients with cT1N0 lung adenocarcinoma who underwent sublobar resection at the authors' institution between 2011 and 2017. A propensity score-matching analysis was used to compared the clinical outcomes between the wedge resection and segmentectomy groups. RESULTS: Wedge resection was performed for 810 patients (80.8%), and segmentectomy was performed for 192 patients (19.2%). Wedge resection resulted in better perioperative outcomes than segmentectomy. The multivariate analysis showed that the significant risk factors for poor disease-free survival (DFS) were elevated preoperative serum carcinoembryonic antigen levels, total tumor diameter greater than 2 cm, and a consolidation-to-tumor (C/T) ratio higher than 50%. After propensity-matching, no differences in overall survival or DFS were noted between the two matched groups. However, subgroup analysis showed that segmentectomy was associated with better DFS than wedge resection (p = 0.039) for the patients with a tumor diameter greater than 2 cm and a C/T ratio higher than 50%. CONCLUSION: Segmentectomy is the appropriate surgical method for sublobar resection in cT1N0 lung adenocarcinoma patients with a tumor diameter greater than 2 cm and a C/T ratio higher than 50%. Wedge resection may be a safe and feasible sublobar resection method for patients with a tumor diameter of 2 cm or smaller or a C/T ratio of 50% or lower.

Detecting small pulmonary nodules with spiral ultrashort echo time sequences in 1.5 T MRI.

OBJECTIVE: This study investigated ultrashort echo time (UTE) sequences in 1.5 T magnetic resonance imaging (MRI) for small lung nodule detection. MATERIALS AND METHODS: A total of 120 patients with 165 small lung nodules before video-associated thoracoscopic resection were enrolled. MRI sequences included conventional volumetric interpolated breath-hold examination (VIBE, scan time 16 s), spiral UTE (TE 0.05 ms) with free-breathing (scan time 3.5-5 min), and breath-hold sequences (scan time 20 s). Chest CT provided a standard reference for nodule size and morphology. Nodule detection sensitivity was evaluated on a lobe-by-lobe basis. RESULTS: The nodule detection rate was significantly higher in spiral UTE free-breathing (> 78%, p < 0.05) and breath-hold sequences (> 75%, p < 0.05) compared with conventional VIBE (> 55%), reaching 100% when nodule size was > 16 mm, and reaching 95% when nodules were in solid morphology, regardless of size. The inter-sequence reliability between free-breathing and breath-hold spiral UTE was good (κ > 0.80). Inter-reader agreement was also high (κ > 0.77) for spiral UTE sequences. Nodule size measurements were consistent between CT and spiral UTE MRI, with a minimal bias up to 0.2 mm. DISCUSSION: Spiral UTE sequences detect small lung nodules that warrant surgery, offers realistic scan times for clinical work, and could be implemented as part of routine lung MRI.

Long-term outcomes after nonintubated versus intubated thoracoscopic lobectomy for clinical stage I non-small cell lung cancer: A propensity-matched analysis.

BACKGROUND: Nonintubated thoracoscopic lobectomy has been described as a feasible surgical treatment for early-stage lung cancer since 2011. Despite promising perioperative results, studies on tumor recurrence and long-term survival are very limited. This study was aimed to compare outcomes after thoracoscopic lobectomy with versus without intubation for stage I non-small cell lung cancer. METHODS: A retrospective data set including 115 and 155 patients who underwent nonintubated and intubated thoracoscopic lobectomy, respectively, between January 2011 and December 2013 was used to identify matched nonintubated and intubated cohorts (n = 97 per group) using a propensity score matching algorithm that accounted for confounding effects of preoperative patient variables. Primary outcome variables included freedom from recurrence and overall survival. Factors affecting survival were assessed using Cox regression analysis and Kaplan-Meier survival estimates. RESULTS: No perioperative mortality occurred in both groups. At an average follow-up of 74 months, comparing nonintubated thoracoscopic lobectomy with intubated procedure, no differences were observed in recurrence rates (14.4% vs. 25.8%, respectively; p = .057). Furthermore, no significant differences were noted in overall survival (97.9% vs. 93.8%, respectively; p = .144). Nonintubated thoracoscopic lobectomy was not found to be an independent predictor of recurrence (hazard ratio, .53; 95% confidence interval [CI], .28-1.02) or overall survival (hazard ratio, .33; 95% CI, .07-1.61). CONCLUSION: In this propensity-matched comparison, nonintubated thoracoscopic lobectomy was not associated with an increased risk for recurrence and overall survival during the 5-year follow-up. However, more randomized trials should be conducted for further validation of these results.

Incidence of chronic thromboembolic pulmonary hypertension in Taiwan.

BACKGROUND: The diagnosis of chronic thromboembolic pulmonary hypertension (CTEPH) is complex, and the modality of treatment is surgery and targeted medication. Patients with CTEPH could have a poor prognosis if their diagnosis or treatment is delayed. The incidence of CTEPH and its clinical features are largely unknown in Taiwan, even among other Asian populations. In this study, we aimed to investigate the geodemographics of CTEPH in Taiwan and describe the practical management and treatment outcomes in patients with CTEPH. METHODS: This study retrospectively enrolled patients in the Taiwan cohort - Registry of CTEPH. The study was conducted over 2 years inclusive of follow-up. The enrolment criteria depended on the current global guideline. RESULTS: From January 2018 to March 2020, 107 CTEPH patients enrolled in the Taiwan registry. All patients received right heart catheterisation examinations. The overall median age was 61.4 ± 16.5 years, and the cohort was dominated by female patients (75/107). Risk factors included pulmonary embolism (81.3%), deep vein thrombosis (22.4%), and previous major surgery (20.6%). Twenty-one (19.6%) patients underwent pulmonary endarterectomy operation alone, and 38 (35.5%) patients underwent balloon pulmonary angioplasty alone. CONCLUSION: To our knowledge, this is the first national cohort study that demonstrated the raw CTEPH incidence in Taiwan. It also showed the CTEPH incidence between male and female patients in the Asian population was different from the Caucasian population.

Efficacy and safety of balloon pulmonary angioplasty in patients with inoperable chronic thromboembolic pulmonary hypertension.

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 < 0.001), and 6-min walk distance improved from 344 ± 147 to 450 ± 120 m (P = 0.014). Additionally, the plasma level of N-terminal pro-brain natriuretic peptide significantly decreased (P = 0.007). Hemodynamic data were available in 11 patients after ≥3 BPA sessions. Both mean pulmonary artery pressure and pulmonary vascular resistance significantly decreased from 44.6 ± 11.7 mmHg to 32.6 ± 5.1 mmHg (P = 0.005) and 745 ± 389 dyn·s·cm-5 to 366 ± 120 dyn·s·cm-5 (P = 0.002), respectively. Cardiac output also increased from 3.69 ± 1.12 L/min to 4.33 ± 0.94 L/min (P = 0.021). CONCLUSION: BPA improved both clinical symptoms and hemodynamic data in inoperable CTEPH Taiwanese patients without major periprocedural complications.

Sirolimus Suppresses Phosphorylation of Cofilin and Reduces Interstitial Septal Thickness in Sporadic Lymphangioleiomyomatosis.

Sporadic lymphangioleiomyomatosis (S-LAM) is a rare lung disease characterized by the proliferation of smooth muscle-like LAM cells and progressive cystic destruction. Sirolimus, a mammalian target of rapamycin (mTOR) inhibitor, has a proven efficacy in patients with LAM. However, the therapeutic mechanisms of sirolimus in LAM remain unclear. We aimed to evaluate sirolimus-related lung parenchymal changes and the potential effect in LAM cells and modulating pathological cystic destruction. Lung specimens were examined for histopathological changes by HMB45 staining and compared the LAM patients treated with and without sirolimus. We detected the overexpression of mTOR, HMB45, and phosphorylation of cofilin (p-cofilin) in LAM patients. Sirolimus showed efficacy in patients with LAM, who exhibited a reduced expression of mTOR and p-cofilin as well as reduced interstitial septal thickness. In addition, sirolimus suppresses mTOR and p-cofilin, thus suppressing the migration and proliferation of LAM cells isolated from the patient's lung tissue. This study demonstrates that interstitial septal thickness, as determined by histological structural analysis. Sirolimus effectively reduced the expression of p-cofilin and interstitial septal thickness, which may be a novel mechanism by sirolimus. Moreover, we develop a new method to isolate and culture the LAM cell, which can test the possibility of medication in vitro and impact this current study has on the LAM field. The development of approaches to interfere with mTOR-cofilin1-actin signaling may result in an option for S-LAM therapy.

The Value of Heart Rhythm Complexity in Identifying High-Risk Pulmonary Hypertension Patients.

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.

Exercise Capacity and Quality of Life in Pulmonary Arterial Hypertension.

BACKGROUND: Pulmonary arterial hypertension (PAH) is a progressive pulmonary vascular disease with a high mortality rate that can be divided into different groups according to etiology and prognosis. Few studies have investigated differences in the exercise capacity and quality of life (QOL) among the different groups of PAH patients. Therefore, we aimed to (1) compare the hemodynamic exercise responses between patients with idiopathic pulmonary arterial hypertension (IPAH) and PAH associated with other diseases (APAH), and (2) determine the factors associated with exercise capacity in patients with PAH. METHODS: Six patients diagnosed with IPAH and eight with APAH [congenital heart disease (CHD)-dominant PAH] were included in this study. The main outcome measures included body composition, exercise capacity, hemodynamic measurements, physical activity levels, fatigue severity, and QOL. RESULTS: The CHD-dominant PAH group had a significantly lower predicted peak oxygen consumption (VO2pred %), pressure of end-tidal carbon dioxide at the peak and at anaerobic threshold (PETCO2peak and PETCO2@AT), and significantly elevated ventilatory equivalent (VE/VCO2slope and VE/VCO2@AT) compared with the IPAH group. Multiple regression analysis indicated that PETCO2@AT was significantly associated with either VO2peak (ß = 0.805, adjusted R2 = 0.619, p = 0.001) or 6-minute walk distance (ß = 0.816, adjusted R2 = 0.638, p < 0.001). CONCLUSIONS: Patients with CHD-dominant PAH had poor exercise capacity and exercise responses compared to those with IPAH. Evaluating exercise capacity and the patient response to exercise using cardiopulmonary exercise testing is increasingly important in view of the etiology of PAH.

Propensity-Matched Analysis Comparing Survival After Sublobar Resection and Lobectomy for cT1N0 Lung Adenocarcinoma.

BACKGROUND: The optimal surgical method for cT1N0 lung adenocarcinoma remains controversial. OBJECTIVE: The aim of this study was to evaluate the differences in clinical outcomes of sublobar resection and lobectomy for cT1N0 lung adenocarcinoma patients. METHODS: We included 1035 consecutive patients with cT1N0 lung adenocarcinoma who underwent surgery at our institute from January 2011 to December 2016. The surgical approach, either sublobar resection or lobectomy, was determined at the discretion of each surgeon. A propensity-matched analysis incorporating total tumor diameter, solid component diameter, consolidation-to-tumor (C/T) ratio, and performance status was used to compare the clinical outcomes of the sublobar resection and lobectomy groups. RESULTS: Sublobar resection and lobectomy were performed for 604 (58.4%; wedge resection/segmentectomy: 470/134) and 431 (41.6%) patients, respectively. Patients in the sublobar resection group had smaller total tumor diameters, smaller solid component diameters, lower C/T ratios, and better performance status. More lymph nodes were dissected in the lobectomy group. Patients in the sublobar resection group had better perioperative outcomes. A multivariable analysis revealed that the solid component diameter and serum carcinoembryonic antigen level are independent risk factors for tumor recurrence. After propensity matching, 284 paired patients in each group were included. No differences in overall survival (OS; p = 0.424) or disease-free survival (DFS; p = 0.296) were noted between the two matched groups. CONCLUSIONS: Sublobar resection is not inferior to lobectomy regarding both DFS and OS for cT1N0 lung adenocarcinoma patients. Sublobar resection may be a feasible surgical method for cT1N0 lung adenocarcinoma.