Next-generation sequencing using tissue specimen collected with a 1.1 mm-diameter cryoprobe in patients with lung cancer.

BACKGROUND AND OBJECTIVE: Next-generation sequencing (NGS) analysis is considered standard for lung cancer diagnosis in clinical practice. Little is known about the feasibility of NGS using tumour tissue sampled with a 1.1 mm-diameter cryoprobe. We aimed to investigate the suitability of specimens obtained by transbronchial cryobiopsy (TBC) using a 1.1 mm-diameter cryoprobe for NGS analysis. METHODS: Patients with lung cancer who underwent TBC using a 1.1 mm-diameter cryoprobe for NGS testing between October 2020 and April 2023 were enrolled. A 4.0- or 3.0 mm-diameter bronchoscope with radial probe endobronchial ultrasound and virtual bronchoscopic navigation was used to detect peripheral lung lesions. All procedures were performed under fluoroscopic guidance. Data were analysed retrospectively. RESULTS: A total of 56 patients underwent TBC using a 1.1 mm cryoprobe for NGS testing, during the study period. Most patients (98%) were in the advanced stage of lung cancer (recurrent or inoperable disease of stages III or IV). The diagnostic yield of NGS for DNA and RNA sequencing was 95% each (53 of 56). Moderate bleeding was noted in three patients (5%) and none of the study patients developed life-threatening complications, such as pneumothorax or lung infection. CONCLUSION: TBC using a 1.1 mm-diameter cryoprobe is a useful and safe tool for NGS analysis, for both DNA and RNA sequencing.

Analysis of 5 years' experience of a head and neck surgeon with radiofrequency ablation for benign thyroid nodule.

PURPOSE: This study reports the long-term efficacy, safety, complications and management of radiofrequency ablation (RFA) for benign thyroid nodule performed over 5 years by a head and neck surgeon. MATERIALS AND METHODS: We studied 287 consecutive patients who underwent RFA between March 2011 and January 2021. Pre- and postoperative thyroid nodule volumes were measured and volume reduction rate was calculated using ultrasonography (USG). Subjective symptom scores and cosmetic scores were investigated. Complications and their managements were analyzed. Complications and their management were investigated. Follow-up USG was performed at 6 and 12 months after RFA, and annually thereafter. RESULTS: The mean volume reduction was 75.2 ± 23.8 % after 6 months and 91.9 ± 14.8 % after 5 years. All of nodule volume, and the cosmetic and symptom scores, decreased significantly postoperatively, and these scores were maintained to 5 years. Minor complications occurred in 15 of 287 (5.2 %) patients; there were no major complications. Injection laryngoplasty was performed for three patients with vocal cord paralysis. Two patients underwent open thyroid surgery because of nodule regrowth. CONCLUSIONS: RFA is a safe and effective treatment without major complication for more than five years. Minor complications were managed by the head-and-neck surgeon personally.

BRAF V600E Mutation of Non-Small Cell Lung Cancer in Korean Patients.

Background and Objectives: BRAF mutational status in resected non-small cell lung cancer (NSCLC) in the Korean population is poorly understood. We explored BRAF (particularly BRAF V600E) mutational status among Korean patients with NSCLC. Materials and Methods: This study included 378 patients with resected primary NSCLC who were enrolled from January 2015 to December 2017. The authors obtained formalin-fixed paraffin-embedded (FFPE) tissue blocks and performed peptide nucleic acid (PNA)-clamping polymerase chain reaction (PCR) for detecting BRAF V600, real-time PCR for detecting BRAF V600E, and immunohistochemical analyses using the mutation-specific Ventana VE1 monoclonal antibody. For positive cases in any methods mentioned above, direct Sanger sequencing was additionally performed. Results: The PNA-clamping method revealed the BRAF V600 mutation in 5 (1.3%) of the 378 patients. Among these five patients, real-time PCR, direct Sanger sequencing detected BRAF V600E mutations in three (0.8%) patients. Thus, two cases showed differences in their PNA-clamping and the others. Direct Sanger sequencing of PNA-clamping PCR product was performed for two cases showing negative results on direct Sanger sequencing; both contained BRAF mutations other than V600E. All patients harboring BRAF mutations had adenocarcinomas, and all patients with V600E mutation exhibited minor micropapillary components. Conclusions: Despite the low incidence of the BRAF mutation among Korean patients with NSCLC, lung adenocarcinoma patients with micropapillary components should be prioritized in terms of BRAF mutation testing. Immunohistochemical staining using Ventana VE1 antibody may serve as a screening examination for BRAF V600E.

Safety and Diagnostic Yield of Radial Probe Endobronchial Ultrasound-Guided Biopsy for Peripheral Lung Lesions in Patients with Idiopathic Pulmonary Fibrosis: A Multicenter Cross-Sectional Study.

BACKGROUND: Radial probe endobronchial ultrasound-guided transbronchial lung biopsy (RP-EBUS-TBLB) is widely used for diagnosis of peripheral lung lesions (PLLs). To date, there have been no reports regarding the clinical outcomes of RP-EBUS-TBLB for PLLs in patients with idiopathic pulmonary fibrosis (IPF). OBJECTIVES: This study was performed between October 2017 and December 2019 to identify the safety and diagnostic performance of RP-EBUS-TBLB in IPF patients. METHODS: Patients were divided into the usual interstitial pneumonia (UIP) group (n = 39, 4%), the probable UIP group (n = 12, 1%), and the noninterstitial lung disease (non-ILD) group (n = 903, 95%). RESULTS: The diagnostic yield was significantly lower in the UIP group than in the non-ILD group (62% vs. 76%; p = 0.042), but there were no significant differences between the UIP and probable UIP groups (62% vs. 83%; p = 0.293) or the probable UIP and non-ILD groups (83% vs. 76%; p = 0.741). Multivariate logistic analysis showed that the mean diameter of PLLs, positive bronchus sign on CT, and "within the lesion" status on EBUS were independently associated with success of the procedure. Especially, the presence of the UIP pattern on CT (OR, 0.385; 95% CI: 0.172-0.863; p = 0.020) was independently associated with failed diagnosis. Among patients with UIP, "within the lesion" status on EBUS (OR, 25.432; 95% CI: 2.321-278.666; p = 0.008) was shown to be a factor contributing to a successful diagnosis. Overall, there were no significant differences in complication rates among the 3 study groups. CONCLUSION: RP-EBUS-TBLB can be performed safely with an acceptable diagnostic yield, even in patients with IPF.

A Life-Threatening Infection after Endobronchial Ultrasound Transbronchial Lung Biopsy with Guide Sheath: A Case Report.

BACKGROUND AND OBJECTIVES: Endobronchial ultrasound transbronchial lung biopsy with guide sheath (EBUS-GS-TBLB) has been regarded as a reasonable diagnostic method with an acceptable diagnostic yield. In addition, EBUS-GS-TBLB is considered safer and less invasive compared to percutaneous needle biopsy and thoracoscopic surgery. However, we encountered a case of life-threatening procedure-related fatal infection, which was successfully managed. CASE PRESENTATION: A 61-year-old man with a 30 pack-year smoking history was referred to our clinic with a necrotic lung mass in the right middle lobe on a chest computed tomography scan. EBUS-GS-TBLB was performed for a pathological diagnosis without immediate complications. Eight days after the procedure, the patient visited the hospital with sudden hemoptysis and severe dyspnea with fever. A chest computed tomography revealed a ruptured lung abscess and pneumonia, developed after EBUS-GS-TBLB. Extracorporeal membrane oxygenation (ECMO) and mechanical ventilation were initiated to manage refractory hypoxia. While maintaining ECMO, video-assisted thoracoscopic surgery was performed at the patient's bedside in the intensive care unit. After surgery, the patient's vital signs gradually improved, and a chest computed tomography revealed a reduction in the extent of the lung abscess. RESULTS: Although EBUS-GS-TBLB is minimally invasive and relatively safe when used for the diagnosis of peripheral lung lesions, pulmonary physicians should be aware of this rare but critical complication. CONCLUSIONS: We suggest that the careful prescription of prophylactic antibiotics before EBUS-GS-TBLB would be wise if the mass featured a necrotic, cavitary, or cystic lesion.

An increasing trend of the number of meniscus allograft transplantation in Korea.

PURPOSE: Meniscus allograft transplantation (MAT) can be performed to treat symptomatic patients with meniscus-deficient knees. However, the current epidemiologic status of MAT is unknown in many countries, including Korea. This study aimed to investigate the national trends of MAT in Korea which covers MAT procedures by the Korean national health insurance system. METHODS: Information from the national database was acquired through the Korean Health Insurance Review and Assessment Service (HIRA) from 2010 to 2017. All patients encoded as MAT were included. The total number of MATs and their incidence per 100,000 persons were determined, and the results were stratified by age and sex. RESULTS: The total number of MATs and their incidence per 100,000 persons per year were 369 and 0.77, respectively, in 2010, which increased to 826 and 1.72, respectively, in 2017. The number of MATs increased by 124% over 8 years. The peaks for the total number of MATs and their incidence were seen in patients in their 20 s in 2010, but in 2017, the peaks were observed in patients who were in their 40 s. MAT was performed more frequently in males (61%) than in females (39%) over the study period. CONCLUSION: The total number of MATs and their incidence had increased by 124% between 2010 and 2017. The peak treatment age range for MAT changed from 20 years of age in 2010 to 40 years of age in 2017, and MAT was performed more frequently in males than in females. LEVEL OF EVIDENCE: IV.

The Preventive Effect of the Phenotype of Tumour-Associated Macrophages, Regulated by CD39, on Colon Cancer in Mice.

BACKGROUND: This study was designed to investigate the effect of cluster differentiation (CD)39 and CD73 inhibitors on the expresion of tumour-associated macrophages (TAMs), M1- versus M2-tumour phenotypes in mice with colon cancer. METHODS: An in vivo study of co-culture with colon cancer cells and immune cells from the bone marrow (BM) of mice was performed. After the confirmation of the effect of polyoxotungstate (POM-1) as an inhibitor of CD39 on TAMs, the mice were randomly divided into a control group without POM-1 and a study group with POM-1, respectively, after subcutaneous injection of CT26 cells. On day 14 after the injection, the mice were sacrificed, and TAMs were evaluated using fluorescence-activated cell sorting. RESULTS: In the in vivo study, the co-culture with POM-1 significantly increased the apoptosis of CT26 cells. The cell population from the co-culture with POM-1 showed significant increases in the expression of CD11b+ for myeloid cells, lymphocyte antigen 6 complex, locus C (Ly6C+) for monocytes, M1-tumour phenotypes from TAMs, and F4/80+ for macrophages. In the in vivo study, tumour growth in the study group with POM-1 was significantly limited, compared with the control group without POM-1. The expressions of Ly6C+ and major histocompatibility complex class II+ for M1-tumour phenotypes from TAMs on F4/80+ from the tumour tissue in the study group had significantly higher values compared with the control group. CONCLUSION: The inhibition of CD39 with POM-1 prevented the growth of colon cancer in mice, and it was associated with the increased expression of M1-tumour phenotypes from TAMs in the cancer tissue.

Patterns of sensitization to aeroallergens and their effect on airway hyper-responsiveness in Busan, Korea.

BACKGROUND: Allergen sensitization and its influence on allergic disease can vary depending on ethnicity and geography. OBJECTIVE: To investigate aeroallergen sensitization patterns and their effect on airway hyper-responsiveness (AHR) in Busan, Korea. METHODS: We reviewed data for subjects who attended for evaluation of respiratory symptoms between 2011 and 2016. The skin test results of 16 allergens (Dermatophagoides pteronyssinus, Dermatophagoides farinae, cat, dog, Alternaria, Aspergillus fumigatus, early blossoming tree pollen mix, late blossoming tree pollen mix, alder, birch, oak, grass mix, mugwort, ragweed, and Japanese hop) were analyzed. Age was categorized as group I (15 to < 65 years) or group II (≥ 65 years). RESULTS: A total of 2,791 subjects were analyzed (mean age: 50.9 years, female 61.3%). AHR was demonstrated in 15.8%; sputum eosinophilia in 12.1%; and atopy in 31.2%. The most commonly sensitizing allergen was house dust mite (17.4% to D. pteronyssinus and 17.9% to D. farinae), followed by late blossoming tree pollen mix (8.8%) and early blossoming tree pollen mix (8.6%). AHR was associated with sensitization to D. pteronyssinus, D. farina, Alternaria, dog, cat, alder, birch, oak, and mugwort. However, group II did not show any associations between AHR and any of the aeroallergens except D. farina. Multiple logistic regression analyses showed that the independent factors for AHR were ever-smoker status, D. farina, and oak sensitization. CONCLUSIONS: Sensitization to house dust mites and tree pollen was found to be common in Busan. These aeroallergens significantly affected AHR, particularly in the younger group.

Genetic Variant of Notch Regulator DTX1 Predicts Survival After Lung Cancer Surgery.

BACKGROUND: We evaluated the association between genetic variants in the Notch pathway and survival outcomes of patients with surgically resected NSCLC. METHODS: Sixty-four single nucleotide polymorphisms (SNPs) in the Notch pathway genes were evaluated in the discovery study (n = 354) and two sequential validation studies (n = 772 and n = 746, respectively). The association of genotype with overall survival (OS) and disease-free survival (DFS) was evaluated. RESULTS: Of the 64 SNPs analyzed in the discovery study, 9 were significantly associated with OS or DFS. Among them, the association remained significant only for Deltex-1 (DTX1) rs1732786A>G in the first validation study. The second validation study confirmed again the association between DTX1 rs1732786A>G and survival outcomes. In the combined analysis, rs1732786A>G was significantly associated with better OS and DFS (adjusted HR ·aHR· for OS, 0.75; 95% CI 0.64-0.87; P = 0.0002; aHR for DFS, 0.79; 95% CI 0.71-0.89; P = 0.0001). In vitro luciferase assay showed that the rs1732786G allele was associated with higher promoter activity compared to rs1732786A allele. Consistently, relative mRNA expression level of DTX1 showed significant positive correlation with rs1732786 A-to-G change (Ptrend = 0.02) in tumor tissues. CONCLUSIONS: These results suggest that DTX1 rs1732786 is a potential prognostic factor that may have clinical utility in the management of early stage NSCLC.

Clinical outcomes of radial probe endobronchial ultrasound using a guide sheath for diagnosis of peripheral lung lesions in patients with pulmonary emphysema.

BACKGROUND: Generally, structural destruction of lung parenchyma, such as pulmonary emphysema, is considered to be related to the low diagnostic yields and high complication rates of lung biopsies of peripheral lung lesions. Currently, little is known about the clinical outcomes of using endobronchial ultrasound with a guide sheath (EBUS-GS) to diagnose peripheral lesions in patients with emphysema. METHODS: This retrospective study was performed to identify the clinical outcomes of EBUS-GS in patients with pulmonary emphysema. This study included 393 consecutive patients who received EBUS-GS between February 2017 and April 2018. The patients were classified according to the severity of their emphysema, and factors possibly contributing to a successful EBUS-GS procedure were evaluated. RESULTS: The overall diagnostic yield of EBUS-GS in patients with no or mild emphysema was significantly higher than in those with moderate or severe pulmonary emphysema (78% vs. 61%, P = 0.007). There were no procedure-related complications. The presence of a bronchus sign on CT (P <  0.001) and a "within the lesion" status on EBUS (P = 0.009) were independently associated with a successful EBUS-GS procedure. Although the diagnostic yield of EBUS-GS in patients with moderate-to-severe emphysema was relatively low, a bronchus sign and "within the lesion" status on EBUS were contributing factors for a successful EBUS-GS. CONCLUSIONS: EBUS-GS is a safe procedure with an acceptable diagnostic yield, even when performed in patients with pulmonary emphysema. The presence of a bronchus sign and "within the lesion" status on EBUS were predictors of a successful procedure.

Bronchoscopic management of solitary bronchial myelolipoma: a case report.

BACKGROUND: Myelolipoma is a rare benign tumor composed of mature adipose and hematopoietic tissues. Most myelolipomas are found in the adrenal glands, whereas intrathoracic myelolipoma is extremely rare. In particular, bronchial myelolipoma without the involvement of lung parenchyma has never been reported. CASE PRESENTATION: A previously healthy 38-year-old male developed dyspnea and a productive cough. Computed tomography revealed an endobronchial mass at the right bronchus intermedius and subsequent atelectasis of the right middle and lower lobes. Flexible bronchoscopy found a total obstruction of the right bronchus intermedius due to an endobronchial tumor. Using a rigid bronchoscope, the endobronchial tumor was resected and the base of the tumor was additionally ablated with a diode laser to prevent recurrence. The removed endobronchial tumor was a 13 mm × 20 mm-sized oval-shaped mass and was pathologically diagnosed as bronchial myelolipoma. Chest radiographs, obtained on the day following the procedure, showed an improvement of atelectasis, and accompanying symptoms were immediately improved. Follow-up bronchoscopy performed after 12 months evidenced no recurrence of the bronchial myelolipoma. CONCLUSIONS: We used bronchoscopic intervention in patients with solitary bronchial myelolipoma and there was no evidence of recurrence.

Depression is a major determinant of both disease-specific and generic health-related quality of life in people with severe COPD.

The quality of life of patients with chronic obstructive pulmonary disease (COPD) decreases significantly as the disease progresses; those with severe COPD are affected most. This article investigates predictors of the disease-specific and generic health-related quality of life (HRQL) in patients with severe COPD. This multicentre prospective cross-sectional study enrolled 80 patients with severe COPD. At enrolment, all patients completed a disease-specific instrument, the St George's Respiratory Questionnaire (SGRQ), and a generic instrument, the Short Form 36 Health Survey Questionnaire (SF-36). The data were analyzed by Pearson's correlation and multiple linear regression. The mean age of the patients was 66 ± 8 years; 93% were males. The SGRQ and SF-36 scores were not influenced by age or sex. Depression, dyspnea, the number of exacerbations, and exercise capacity significantly predicted the total SGRQ score ( p < 0.05). Depression was the strongest determinant of the total SGRQ score. The SF-36 physical component summary scores were related to depression, dyspnea, and the number of exacerbations ( p < 0.05). In comparison, the SF-36 mental component summary scores were related to depression and anxiety ( p < 0.05). Depression is a significant determinant of both the disease-specific and generic HRQL in patients with severe COPD. Screening and early intervention for depression in patients with severe COPD could improve the HRQL.

Pleurodesis Using Mistletoe Extract Delivered via a Spray Catheter during Semirigid Pleuroscopy for Managing Symptomatic Malignant Pleural Effusion.

BACKGROUND: Talc poudrage during thoracoscopy is considered the standard procedure for patients with symptomatic malignant pleural effusion (MPE). Until now, no alternative technique other than talc poudrage for pleurodesis during medical thoracoscopy has been proposed. Liquid sclerosants, such as mistletoe extract, have been sprayed evenly into the pleural cavity during semirigid pleuroscopy for chemical pleurodesis. OBJECTIVE: We conducted a retrospective study using the database of semirigid pleuroscopy to identify the usefulness of pleurodesis using a mistletoe extract delivered via a spray catheter during semirigid pleuroscopy for symptomatic MPE. METHODS: All consecutive patients with symptomatic MPE who underwent semirigid pleuroscopy from October 2015 to September 2016 were registered. The responses were evaluated using chest X- ray or computed tomography 4 weeks after pleurodesis. RESULTS: The study included 43 patients who underwent pleurodesis with mistletoe extract via a spray catheter during semirigid pleuroscopy. Complete and partial responses were seen in 21 (49%) and 19 (44%) patients, respectively. The median duration of chest tube placement after pleurod-esis was 7 days (range 6-8 days) in the 40 patients with complete or partial responses. No cases of severe hemorrhage, empyema formation, respiratory failure, or procedure-related mortality were observed in the subjects at 4 weeks after semirigid pleuroscopy. CONCLUSION: Pleurodesis with mistletoe extract delivered via a spray catheter during semirigid pleuroscopy is a safe and effective procedure for managing symptomatic MPE.

Radial probe endobronchial ultrasound using a guide sheath for peripheral lung lesions in beginners.

BACKGROUND: The diagnostic yields and safety profiles of transbronchial lung biopsy have not been evaluated in inexperienced physicians using the combined modality of radial probe endobronchial ultrasound and a guide sheath (EBUS-GS). This study assessed the utility and safety of EBUS-GS during the learning phase by referring to a database of performed EBUS-GS procedures. METHODS: From December 2015 to January 2017, all of the consecutive patients who underwent EBUS-GS were registered. During the study period, two physicians with no previous experience performed the procedure. To assess the diagnostic yields, learning curve, and safety profile of EBUS-GS performed by these inexperienced physicians, the first 100 consecutive EBUS-GS procedures were included in the evaluation. RESULTS: The overall diagnostic yield of EBUS-GS performed by two physicans in 200 patients with a peripheral lung lesion was 73.0%. Learning curve analyses showed that the diagnostic yields were stable, even when the procedure was performed by beginners. Complications related to EBUS-GS occurred in three patients (1.5%): pneumothorax developed in two patients (1%) and resolved spontaneously without chest tube drainage; another patient (0.5%) developed a pulmonary infection after EBUS-GS. There were no cases of pneumothorax requiring chest tube drainage, severe hemorrhage, respiratory failure, premature termination of the procedure, or procedure-related mortality. CONCLUSIONS: EBUS-GS is a safe and stable procedure with an acceptable diagnostic yield, even when performed by physicians with no previous experience.

Improved Method for Reliable HMW-GS Identification by RP-HPLC and SDS-PAGE in Common Wheat Cultivars.

The accurate identification of alleles for high-molecular weight glutenins (HMW-GS) is critical for wheat breeding programs targeting end-use quality. RP-HPLC methods were optimized for separation of HMW-GS, resulting in enhanced resolution of 1By and 1Dx subunits. Statistically significant differences in retention times (RTs) for subunits corresponding to HMW-GS alleles were determined using 16 standard wheat cultivars with known HMW-GS compositions. Subunits that were not identified unambiguously by RP-HPLC were distinguished by SDS-PAGE or inferred from association with linked subunits. The method was used to verify the allelic compositions of 32 Korean wheat cultivars previously determined using SDS-PAGE and to assess the compositions of six new Korean cultivars. Three cultivars contained subunits that were identified incorrectly in the earlier analysis. The improved RP-HPLC method combined with conventional SDS-PAGE provides for accurate, efficient and reliable identification of HMW-GS and will contribute to efforts to improve wheat end-use quality.

Clinical utility of rapid pathogen identification using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry in ventilated patients with pneumonia: A pilot study.

BACKGROUND AND OBJECTIVE: We evaluated the clinical utility of rapid identification of microorganisms in bronchoalveolar lavage (BAL) fluid using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) in terms of the clinical outcomes of ventilated patients with pneumonia. METHODS: Patients for whom microorganisms were identified via MALDI-TOF MS (from March 2013 to February 2014; post-intervention group) were compared with patients for whom microorganisms were identified using conventional methods (from March 2012 to February 2013; pre-intervention group). All pneumonia types (community-acquired, hospital-acquired, healthcare-associated and ventilator-associated pneumonia) were included in the analysis. RESULTS: In total, 77 patients (50 men, mean age 67.2 ± 12.5 years) were included (40 patients in the pre-intervention group and 37 in the post-intervention group). The time from BAL fluid collection to microorganism identification and the availability of antimicrobial susceptibility results was shorter in the post- compared with the pre-intervention group (51.9 ± 11.3 vs 67.3 ± 17.4 h, P < 0.001). Also, the time from BAL fluid collection to adjustment of antibiotic therapy was shorter in the post-intervention group (56.5 ± 10.9 vs 73.2 ± 18.5 h, P < 0.001). Microorganism identification via MALDI-TOF MS was independently associated with a shorter intensive care unit (ICU) stay after BAL fluid was drawn (hazard ratio = 2.324, P = 0.007). CONCLUSION: Rapid identification of microorganisms in BAL fluid via MALDI-TOF MS was associated with adjustment of antibiotic therapy and a shorter ICU stay after BAL fluid was collected from ventilated patients with pneumonia.

Once-Daily OROS Hydromorphone for Management of Cancer Pain: an Open-Label, Multi-Center, Non-Interventional Study.

Extended-release osmotic extended-release oral delivery system (OROS) hydromorphone is a strong synthetic opioid designed to maintain a constant blood concentration by once daily dosing. The objective of this observational study was to investigate the clinical usefulness of OROS hydromorphone in patients with cancer pain of moderate to severe intensity. Patients with cancer pain who required strong opioids were administered with OROS hydromorphone for 4 weeks. We assessed changes in pain intensity using a numerical rating scale (NRS) as well as levels of sleep disturbance, breakthrough pain, end-of-dose failure, patient satisfaction, and overall assessment of drug effectiveness based on investigator evaluation. Of the 648 enrolled patients, 553 patients were included in the full analysis set. The mean pain intensity was significantly decreased from the NRS value of 5.07 ± 1.99 to 2.75 ± 1.94 (mean % change of 42.13 ± 46.53, P < 0.001). The degree of sleep disturbance significantly improved (mean NRS change of 1.61 ± 2.57, P < 0.001), and the incidence of breakthrough pain was significantly decreased (mean NRS change of 1.22 ± 2.30, P < 0.001). The experience of end-of-dose failure also significantly decreased from 4.60 ± 1.75 to 3.93 ± 1.70, P = 0.007). The patient satisfaction rate was 72.7%, and 72.9% of investigators evaluated the study drug as effective. OROS hydromorphone was an effective and tolerable agent for cancer pain management. It effectively lowered pain intensity as well as improved sleep disturbance, breakthrough pain, and end-of-dose failure.

Upconversion Nanoparticle-Based Förster Resonance Energy Transfer for Detecting DNA Methylation.

Aberrant methylation of a crucial CpG island is the main mechanism for the inactivation of CDKN2A in the early stages of carcinogenesis. Therefore, the detection of DNA methylation with high sensitivity and specificity is important, and various detection methods have been developed. Recently, upconversion nanoparticles (UCNPs) have been found to display a high signal-to-noise ratio and no photobleaching, making them useful for diagnostic applications. In this pilot study, we applied UCNPs to the detection of CDKN2A methylation and evaluated the feasibility of this system for use in molecular diagnostics. DNA PCR was performed using biotinylated primers, and the PCR amplicon was then intercalated with SYTOX Orange dye, followed by incubation with streptavidin-conjugated UCNPs. Fluorescence detection of the Förster resonance energy transfer (FRET) of the UCNPs (MS-UC-FRET) was then performed, and the results were compared to those from real-time PCR (RQ-PCR) and pyrosequencing. Detection by MS-UC-FRET was more sensitive than that by either RQ-PCR or pyrosequencing. Our results confirmed the success of our MS-UC-FRET system for detecting DNA methylation and demonstrated the potential application of this system in molecular diagnostics.

Efficacy of TB-PCR using EBUS-TBNA samples in patients with intrathoracic granulomatous lymphadenopathy.

BACKGROUND: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is widely used to perform mediastinal lymph node sampling. However, little information is available on polymerase chain reaction for Mycobacterium tuberculosis (TB-PCR) using EBUS-TBNA samples in patients with intrathoracic granulomatous lymphadenopathy (IGL). METHODS: A retrospective study using a prospectively collected database was performed from January 2010 to December 2014 to evaluate the efficacy of the TB-PCR test using EBUS-TBNA samples in patients with IGL. During the study period, 87 consecutive patients with isolated intrathoracic lymphadenopathy who received EBUS-TBNA were registered and 46 patients with IGL were included. RESULTS: Of the 46 patients with IGL, tuberculous lymphadenitis and sarcoidosis were diagnosed in 16 and 30 patients, respectively. The sensitivity, specificity, positive predictive value, and negative predictive value of TB-PCR for tuberculous lymphadenitis were 56, 100, 100, and 81%, respectively. The overall diagnostic accuracy of TB-PCR for tuberculous lymphadenitis was 85%. In addition, seven (17%) patients had non-diagnostic results from a histological examination and all of them had non-diagnostic microbiological results of an acid-fast bacilli smear and culture. Four (57%) of the seven patients with non-diagnostic results had positive TB-PCR results, and anti-tuberculosis treatment led to clinical and radiological improvement in all of the patients. CONCLUSIONS: TB-PCR using EBUS-TBNA samples is a useful laboratory test for diagnosing IGL. Moreover, this technique can prevent further invasive evaluation in patients whose histological and microbiological tests are non-diagnostic.

Association of depression with disease severity in patients with chronic obstructive pulmonary disease.

PURPOSE: Patients with chronic obstructive pulmonary disease (COPD), which is predicted to be the third most common cause of death worldwide by 2020, often suffer from depression, one of the most common and modifiable comorbidities of COPD. This study assessed the prevalence of depression in patients with COPD and the association of depression with disease severity. METHODS: This was a multicenter, prospective cross-sectional study of 245 patients with stable COPD. Disease severity was assessed using two scales: the global initiative for chronic obstructive lung disease (GOLD) stage and BODE index. Depression was measured using the Centers for Epidemiologic Studies Depression (CES-D) scales. Data were analyzed using descriptive statistics, Spearman correlation, and multivariate logistic regression. RESULTS: Depression defined as a CES-D score of 24 and higher was observed in 17.6 % of patients with COPD. The prevalence of depression increased with disease severity based on the BODE quartile (r = 0.16; P = 0.014). By contrast, no difference was observed in the prevalence of depression among the severity groups using the GOLD staging system (r = - 0.01; P = 0.898). Elementary school graduates were more likely to experience depression than graduates of high school and above [odds ratio (OR) = 3.67; 95 % confidence interval (CI) 1.37-9.85] and patients in BODE quartile II were more likely to experience depression than those with BODE quartile I (OR = 2.5; 95 % CI  1.04-6.06). CONCLUSIONS: Depression was associated with disease severity according to the BODE quartile in patients with COPD. BODE quartile II was a significant predictor of depression. Screening patients with a high risk of depression and proactive intervention for those patients are needed.