Prevalence and clinical characteristics of Sarcopenia in older adult patients with stable chronic obstructive pulmonary disease: a cross-sectional and follow-up study.

BACKGROUND: The relationship between sarcopenia and chronic obstructive pulmonary disease (COPD) has been increasingly reported, and there is some overlap regarding their clinical features and pulmonary rehabilitation (PR) strategies. No Korean study has reported the actual prevalence of sarcopenia in patients with stable COPD who are recommended for pulmonary rehabilitation. This study evaluated the prevalence and clinical features of sarcopenia in older adult outpatients with stable COPD and the changes after 6 months. METHODS: In this cross-sectional and 6-month follow-up study, we recruited 63 males aged ≥ 65 diagnosed with stable COPD. Sarcopenia was diagnosed using the AWGS 2019 criteria, which included hand grip strength testing, bioelectrical impedance analysis, Short Physical Performance Battery administration, and Strength, Assistance with walking, Rising from a chair, Climbing stairs, and Falling screening tool administration. A 6-minute walk test (6 MWT) was conducted, forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), maximal inspiratory and expiratory pressures (MIP and MEP, respectively) and peak expiratory flow (PEF) were assessed, and patient-reported questionnaires were administered. RESULTS: At baseline, 14 (22%) patients were diagnosed with possible sarcopenia, and eight (12.6%) were diagnosed with sarcopenia. There were significant differences in the age; body mass index; Body mass index, airflow Obstruction, Dyspnea, and Exercise index; modified Medical Research Council dyspnea scores; and International Physical Activity Questionnaire scores between the normal and sarcopenia groups. Whole-body phase angle, MIP, MEP, PEF, and 6-minute walk distance (6 MWD) also showed significant differences. Over 6 months, the proportion of patients with a reduced FEV1 increased; however, the proportion of patients with sarcopenia did not increase. CONCLUSION: A relatively low prevalence of sarcopenia was observed in older adult outpatients with stable COPD. No significant change in the prevalence of sarcopenia was found during the 6-month follow-up period. TRIAL REGISTRATION: The study was registered with the Clinical Research Information Service (KCT0006720). Registration date: 30/07/2021.

Predictive Role of White Blood Cell Differential Count for the Development of Acute Exacerbation in Korean Chronic Obstructive Pulmonary Disease.

Purpose: Chronic obstructive pulmonary disease (COPD) is a respiratory disease characterized by chronic inflammation. Acute exacerbation of COPD (AECOPD) manifests as acute worsening of respiratory symptoms and is associated with high morbidity and mortality. The aim of the present study was to evaluate the predictive value of white blood count (WBC) and its derived inflammatory biomarkers for AECOPD. Methods: From the Korean COPD Subgroup Study cohort, a prospective and multicenter observational study, 826 patients who had baseline complete blood count (CBC) and 3-year AECOPD data were included. Follow-up CBC data at 1 (n = 385), 2 (n = 294), and 3 (n = 231) years were collected for available patients. The primary outcome was the occurrence of AECOPD at 3 years. The risk of AECOPD was evaluated using a binary logistic analysis. Results: The cumulative incidences of 12-, 24-, and 36-month AECOPD were 47.6%, 60.5%, and 67.6%, respectively. Patients with AECOPD at 3 years had higher baseline WBC counts, neutrophil counts, neutrophil/lymphocyte ratio (NLR), and neutrophil/monocyte ratio than those without AECOPD. Higher WBC count, neutrophil count, and NLR were associated with the 3-year occurrence of AECOPD in the univariate analysis, but only the higher neutrophil count was a significant risk factor (odds ratio [OR] = 1.468; 95% confidence interval [CI]: 1.024-2.104) in the covariates-adjusted analysis. In the analysis of changes in inflammatory parameters, a decrease in the platelet count (OR = 0.502; 95% CI: 0.280-0.902) and NLR (OR = 0.535; 95% CI: 0.294-0.974) at 2 years and an increase in the eosinophil count (OR = 2.130; 95% CI: 1.027-4.416) at 3 years were significantly associated with AECOPD in the adjusted analysis. Conclusion: Our data suggest that a high baseline WBC count, particularly neutrophil count, was associated with a higher incidence of long-term AECOPD.

Pulmonary Rehabilitation Is Associated With Decreased Exacerbation and Mortality in Patients With COPD: A Nationwide Korean Study.

BACKGROUND: Poor uptake to pulmonary rehabilitation (PR) is still challenging around the world. There have been few nationwide studies investigating whether PR impacts patient outcomes in COPD. We investigated the change of annual PR implementation rate, medical costs, and COPD outcomes including exacerbation rates and mortality between 2015 and 2019. RESEARCH QUESTION: Does PR implementation improve outcomes in patients with COPD in terms of direct cost, exacerbation, and mortality? STUDY DESIGN AND METHODS: Data of patients with COPD extracted from a large Korean Health Insurance Review and Assessment service database (2015-2019) were analyzed to determine the trends of annual PR implementation rate and direct medical costs of PR. Comparison of COPD exacerbation rates between pre-PR and post-PR, and the time to first exacerbation and mortality rate according to PR implementation, were also assessed. RESULTS: Among all patients with COPD in South Korea, only 1.43% received PR. However, the annual PR implementation rate gradually increased from 0.03% to 1.4% during 4 years, especially after health insurance coverage commencement. The direct medical cost was significantly higher in the PR group than the non-PR group, but the costs in these groups showed decreasing and increasing trends, respectively. Both the incidence rate and frequency of moderate-to-severe and severe exacerbations were lower during the post-PR period compared with the pre-PR period. The time to the first moderate-to-severe and severe exacerbations was longer in the PR group than the non-PR group. Finally, PR implementation was associated with a significant decrease in mortality. INTERPRETATION: We concluded that health insurance coverage increases PR implementation rates. Moreover, PR contributes toward improving outcomes including reducing exacerbation and mortality in patients with COPD. However, despite the well-established benefits of PR, its implementation rate remains suboptimal.

Clinical outcomes of transbronchial cryobiopsy using a 1.1-mm diameter cryoprobe for peripheral lung lesions - A prospective pilot study.

OBJECTIVES: Transbronchial cryobiopsy (TBCB) is a novel technique for the diagnosis of peripheral lung lesions (PLLs). We aim to evaluate the clinical outcomes of TBCB using a new 1.1-mm diameter cryoprobe for the diagnosis of PLLs. MATERIALS AND METHODS: We performed a prospective observational pilot study on the diagnosis of PLLs (diameter ≤30 mm) by TBCB, using a 1.1-mm diameter cryoprobe with radial endobronchial ultrasound (RP-EBUS), virtual bronchoscopic navigation and fluoroscopy from December 2021 to July 2022. Primary outcome was the pathological diagnostic yield of TBCB, and secondary outcome was adverse event. RESULTS: A total of 50 patients were enrolled (mean lesion size, 21 mm). TBCB was performed in 49 patients up to three times except for the one with "invisible" finding on RP-EBUS. The overall diagnostic yield of TBCB was 90% (45/50). There was no difference in the diagnostic yield between size (20 mm vs. 20-30 mm; 88% [22/25] vs. 92% [23/25]; P = 1.000), RP-EBUS findings (concentric vs. others; 97% [28/29] vs. 81% [17/21]; P = 0.148), and acute angle location (apical segment of both upper lobes vs. others; 92% [12/13] vs. 89% [33/37]; P = 1.000). The cumulative diagnostic yields of the first, second, and third TBCB were 82% (41/50), 88% (44/50), and 90% (45/50), respectively. Mild bleeding was developed in 56% (28/50), and moderate bleeding was found in 26% (13/50). CONCLUSION: TBCB using a 1.1-mm diameter cryoprobe is an effective, reasonable method for the diagnosis of PLLs regardless of its size, RP-EBUS finding, and anatomical location without serious complication. TRIAL REGISTRATION: Clinical Trials.Gov (NCT05046093).

The Protective Role of Exosome-Derived MicroRNAs and Proteins from Human Breast Milk against Infectious Agents.

Human breast milk (HBM)-derived exosomes contain various biological and immunological components. However, comprehensive immune-related and antimicrobial factor analysis requires transcriptomic, proteomic, and multiple databases for functional analyses, and has yet to be conducted. Therefore, we isolated and confirmed HBM-derived exosomes by detecting specific markers and examining their morphology using western blot and transmission electron microscopy. Moreover, we implemented small RNA sequencing and liquid chromatography-mass spectrometry to investigate substances within the HBM-derived exosomes and their roles in combating pathogenic effects, identifying 208 miRNAs and 377 proteins associated with immunological pathways and diseases. Integrated omics analyses identified a connection between the exosomal substances and microbial infections. In addition, gene ontology and the Kyoto Encyclopedia of Genes and Genomes pathway analyses demonstrated that HBM-derived exosomal miRNA and proteins influence immune-related functions and pathogenic infections. Finally, protein-protein interaction analysis identified three primary proteins (ICAM1, TLR2, and FN1) associated with microbial infections mediating pro-inflammation, controlling infection, and facilitating microbial elimination. Our findings determine that HBM-derived exosomes modulate the immune system and could offer therapeutic strategies for regulating pathogenic microbial infection.

Changes in microRNAs during Storage and Processing of Breast Milk.

Human breast milk (HBM) is the ideal source of nutrients for infants and is rich in microRNA (miRNA). In recent years, expressed breast milk feeding rather than direct breastfeeding has become increasingly prevalent for various reasons. Expressed HBM requires storage and processing, which can cause various changes in the ingredients. We investigated how the miRNAs in HBM change due to processes often used in real life. HBM samples collected from 10 participants were each divided into seven groups according to the storage temperature, thawing method, and storage period. In addition, we analyzed the miRNA changes in each group. The number of microRNAs that showed significant expression was not large compared to the thousands of miRNAs contained in breast milk. Therefore, it is difficult to suggest that the various storage and thawing processes have a great influence on the overall expression of miRNA. However, a short-term refrigeration storage method revealed little change in nutrients compared to other storage and thawing methods. Taking all factors into consideration, short-term refrigeration is recommended to minimize changes in the composition or function of breast milk.

Real-world evaluation of atezolizumab and etoposide-carboplatin as a first-line treatment for extensive-stage small cell lung cancer.

BACKGROUND/AIMS: Despite the obvious benefits of adding immune checkpoint inhibitors to platinum-etoposide chemotherapy in patients with extensive-stage small-cell lung cancer (ES-SCLC), real-world data remain scarce. METHODS: This retrospective study included 89 patients with ES-SCLC treated with platinum-etoposide chemotherapy alone (chemo-only group; n = 48) or in combination with atezolizumab (atezolizumab group; n = 41) and compared the survival outcomes between these two groups. RESULTS: Overall survival (OS) was significantly longer in the atezolizumab group than in the chemo-only group (15.2 months vs. 8.5 months; p = 0.047), whereas the median progression-free survival was almost the same (5.1 months vs. 5.0 months) in both groups (p = 0.754). Subsequent multivariate analysis revealed that thoracic radiation (hazard ratio [HR], 0.223; 95% confidence interval [CI], 0.092-0.537; p = 0.001) and atezolizumab administration (HR, 0.350; 95% CI, 0.184-0.668; p = 0.001) were favorable prognostic factors for OS. In the thoracic radiation subgroup, patients who received atezolizumab demonstrated favorable survival outcomes and no grade 3-4 adverse events (AEs). CONCLUSION: The addition of atezolizumab to platinum-etoposide resulted in favorable outcomes in this real-world study. Thoracic radiation was associated with improved OS and acceptable AE risk in combination with immunotherapy in patients with ES-SCLC.

The Additive Impact of Transbronchial Cryobiopsy Using a 1.1-mm Diameter Cryoprobe on Conventional Biopsy for Peripheral Lung Nodules.

PURPOSE: The diagnostic yield of transbronchial biopsy (TBB) using radial probe endobronchial ultrasound (RP-EBUS) is 71%, which is lower than that of transthoracic needle biopsy. We investigated the performance and safety of sequential transbronchial cryobiopsy (TBC) using a novel 1.1-mm diameter cryoprobe, after conventional TBB using RP-EBUS for the diagnosis of peripheral lung lesions (PLLs). Materials and Methods: From April 2021 to November 2021, 110 patients who underwent bronchoscopy using RP-EBUS for the diagnosis of PLL ≤ 30 mm were retrospectively included in our study. All records were followed until June 2022. RESULTS: The overall diagnostic yield of combined TBB and TBC was 79.1%, which was higher than 60.9% of TBB alone (p=0.005). The diagnostic yield of sequential TBC was 65.5%, which increased the overall diagnostic yield by 18.2%. The surface area of tissues by TBC (mean area, 18.5 mm2) was significantly larger than those of TBB by 1.5-mm forceps (3.4 mm2, p < 0.001) and 1.9-mm forceps (3.7 mm2, p=0.011). In the multivariate analysis, PLLs with the longest diameter of ≤ 22 mm were found to be related to additional diagnostic benefits from sequential TBC (odds ratio, 3.51; 95% confidence interval, 1.043 to 11.775; p=0.042). Complications were found in 10.5% of the patients: pneumothorax (1.0%), infection (1.0%), and significant bleeding (8.6%). None of the patients developed any life-threatening complications. CONCLUSION: Sequential TBC with a 1.1-mm cryoprobe improved the performance of conventional TBB using RP-EBUS without serious complications.

Hypofractionated stereotactic radiosurgery for dural arteriovenous fistula in the superior sagittal sinus: case report and review of the literature.

Stereotactic radiosurgery (SRS) for dural arteriovenous fistula (dAVF) in the superior sagittal sinus (SSS) is not an established treatment because of relatively poor efficacy and a latency period for treatment effects. Hypofractionated SRS for these lesions has not yet been reported. A 65-year-old man presented with intermittent paraparesis. Brain magnetic resonance imaging (MRI) revealed acute infarction in the premotor and motor cortex of both frontal convexities. Cerebral angiography demonstrated extensive dAVF in the middle and posterior third SSS, associated with an occlusion in the middle third. Transfemoral arterial Onyx embolization was performed through the right middle meningeal arteries, and cerebral venous reflux (CVR) disappeared from the middle third of the SSS. However, the remnant dAVF in the posterior third of the SSS and CVR in the posterior parietal and occipital lobes remained. Novalis SRS was performed on remnant the dAVF with 35 Gy in 5 fractions. Seven months after Novalis SRS, symptoms improved and cortical engorged vessel gradually disappeared on brain MRI. The patient recovered completely at 22 months post-radiosurgery. SRS for dAVF in the SSS could provide an alternative treatment option. Hypofractionated SRS showed a good result in our case.

Hypofractionated stereotactic radiosurgery for aggressive vertebral haemangioma and useful follow-up imaging modality: case report and review of the literature.

We report the use of an advanced magnetic resonance image (MRI) sequence to detect the treatment response after SRS for aggressive vertebral haemangioma (VH). A 63-year-old female patient presented with back pain, bilateral lower extremity weakness (grade IV), and sensory change in the saddle area. MRI revealed a vertebral body mass compressing the spinal cord at T10, which had high T2 and low T1 signal intensity. Three-dimensional volumetric sagittal time-resolved imaging of contrast kinetics (TRICKS) abdominal magnetic resonance angiography (MRA) showed it to be hypervascular. SRS with the Novalis beam shaping system (BrainLAB; Heimstetten®, Germany) was performed on the gross tumor volume of 14.954 mL. 30 Gy was given to the 90% isodose line in 5 fractions. Seven days later, the patient underwent decompressive laminectomy for weakness. Seven months later, the patient's motor weakness was improved to allow for unassisted gait, and back pain and sensory changes resolved. Follow-up MRI revealed no significant change on T1 and T2 signal intensity images. However, TRICKS abdominal MRA demonstrated disapprearance of the hypervascularity. Seven years after SRS, the same signal intensity images showed shrinkage of the mass and resolution of compression of the spinal cord, and the signal intensity of the T1 image was changed to iso- and high signal intensity.

Emphysema Quantification Using Ultra-Low-Dose Chest CT: Efficacy of Deep Learning-Based Image Reconstruction.

Background and Objectives: Although reducing the radiation dose level is important during diagnostic computed tomography (CT) applications, effective image quality enhancement strategies are crucial to compensate for the degradation that is caused by a dose reduction. We performed this prospective study to quantify emphysema on ultra-low-dose CT images that were reconstructed using deep learning-based image reconstruction (DLIR) algorithms, and compared and evaluated the accuracies of DLIR algorithms versus standard-dose CT. Materials and Methods: A total of 32 patients were prospectively enrolled, and all underwent standard-dose and ultra-low-dose (120 kVp; CTDIvol < 0.7 mGy) chest CT scans at the same time in a single examination. A total of six image datasets (filtered back projection (FBP) for standard-dose CT, and FBP, adaptive statistical iterative reconstruction (ASIR-V) 50%, DLIR-low, DLIR-medium, DLIR-high for ultra-low-dose CT) were reconstructed for each patient. Image noise values, emphysema indices, total lung volumes, and mean lung attenuations were measured in the six image datasets and compared (one-way repeated measures ANOVA). Results: The mean effective doses for standard-dose and ultra-low-dose CT scans were 3.43 ± 0.57 mSv and 0.39 ± 0.03 mSv, respectively (p < 0.001). The total lung volume and mean lung attenuation of five image datasets of ultra-low-dose CT scans, emphysema indices of ultra-low-dose CT scans reconstructed using ASIR-V 50 or DLIR-low, and the image noise of ultra-low-dose CT scans that were reconstructed using DLIR-low were not different from those of standard-dose CT scans. Conclusions: Ultra-low-dose CT images that were reconstructed using DLIR-low were found to be useful for emphysema quantification at a radiation dose of only 11% of that required for standard-dose CT.

Risk Factors for Postoperative Pneumonia in the Elderly Following Hip Fracture Surgery: A Systematic Review and Meta-Analysis.

Introduction: Pneumonia is a serious complication following hip fracture surgery in older people. However, the prevalence and risk factors of postoperative pneumonia (POP) are not well-established. This study identified pre- and peri-operative factors associated with the development of POP following hip fracture surgery. Methods: We searched the Cochrane library, PubMed, and Embase databases for relevant articles published up to June 2021. Studies involving older patients who underwent hip fracture surgery were considered if they detailed the demographic or surgical characteristics of the participants. For all analyses, the pooled odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated. Results: A total of 24 studies (288819 participants) were included. The overall prevalence of POP following hip fracture surgery was 5.0%. There were 36 risk factors for POP, and the meta-analysis included the five most common: delayed surgery (OR: 1.84, 95% CI: 1.29-2.63), low serum albumin (OR: 2.34, 95% CI: .82-6.73), chronic respiratory diseases (OR: 2.42, 95% CI: 1.82-3.24), increased age (OR: 1.25, 95% CI:1.11-1.40), and male sex (OR: 2.22, 95% CI: 2.00-2.47). Conclusions: The prevalence of POP was 5.0% following hip fracture surgery in the elderly. Older age, male sex, chronic respiratory diseases, delayed surgery, and low serum albumin were significant risk factors. Clinicians treating hip fracture patients must remain be aware of these risk factors.

The Korean-Lung Information Needs Questionnaire: Translation, validation and clinical implications in comprehensive pulmonary rehabilitation.

PURPOSE: Chronic obstructive pulmonary disease (COPD) is characterized by airflow limitation and persistent respiratory symptoms. Several symptom-related questionnaires have been validated to improve understanding for patient with COPD. We aimed to systematically translate the English version of the Lung Information Needs Questionnaire (LINQ) into Korean and to verify the reliability, validity and clinical implications in comprehensive pulmonary rehabilitation (PR). METHODS: The original version of LINQ was translated into Korean by two translators and reviewed by the translation committee. It was then reverse translated back into English. The committee compared the reconciled version in Korean and the original version in English. A cognitive debriefing was performed on the pre-final version, and a final version, K-LINQ, was obtained. A test-retest method for the analysis of reliability was performed within 2 weeks. Concurrent validity analysis was performed using Pearson correlation test of the K-LINQ and other evaluation tools. RESULTS: A total of 110 patients were enrolled. The length, readability, understanding and suitability of the questionnaire rated well in scores for face validity of 52 Korean patients with COPD. No significant correlation was derived from the total K-LINQ and each domain with other scales such as mMRC, K-CAT and K-LCADL. The intra-class correlation coefficient of total score K-LINQ showed high reliability. Patients who attended PR showed significantly poor pulmonary function or more severe symptoms. In addition, a significantly lower score in total score and exercise domain of K-LINQ were confirmed in the group of PR attendees. CONCLUSIONS: We translated the LINQ into Korean, implemented cross-cultural adaptation and verified its validity and reliability. K-LINQ can now be useful in various clinical and research fields in the Republic of Korea and could serve a complementary role and become an axis of successful treatment strategies, including a comprehensive PR programme.

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.

Cancer Testis Antigen, NOL4, Is an Immunogenic Antigen Specifically Expressed in Small-Cell Lung Cancer.

To identify cancer/testis (CT) antigens and immunogenic proteins, immunoscreening of testicular and small-cell lung cancer cell line NCI-H889 cDNA libraries was performed using serum obtained from a small-cell lung cancer (SCLC) patient. We obtained 113 positive cDNA clones comprised of 74 different genes, designated KP-SCLC-1 through KP-SCLC-74. Of these genes, 59 genes were found to be related to cancers by EMBASE analysis. Three of these antigens, including KP-SCLC-29 (NOL4), KP-SCLC-59 (CCDC83), and KP-SCLC-69 (KIF20B), were CT antigens. RT-PCR and western blot analysis showed that NOL4 was frequently present in small-cell lung cancer cell lines (8/9, 8/9). In addition, NOL4 mRNA was weakly, or at a low frequency, or not detected in various cancer cell lines. Our results reveal that NOL4 was expressed at protein levels in small-cell lung cancer tissues (10/10) but not detected in lung adenocarcinoma and squamous cell carcinoma by immunohistochemical analysis. Serological response to NOL4 was also evaluated by western blot assay using NOL4 recombinant protein. A humoral response against NOL4 proteins was detected in 75% (33/44) of small-cell lung cancer patients and in 65% (13/20) of healthy donors by a serological western blot assay. These data suggest that NOL4 is a specific target that may be useful for diagnosis and immunotherapy in SCLC.

Treatments of inflammatory bowel disease toward personalized medicine.

Inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn's disease (CD), is a chronic inflammatory disease characterized by intestinal inflammation and epithelial injury. For the treatment of IBD, 5-aminosalicylic acids, corticosteroids, immunomodulators, and biologic agents targeting tumor necrosis factor (TNF)-α, α4ß7-integrin, and interleukin (IL)-12/23 have been widely used. Especially, anti-TNF-α antibodies are the first biologic agents that presently remain at the forefront. However, 10-30% of patients resist biologic agents, including anti-TNF-α agents (primary non-responder; PNR), and 20-50% of primary responders develop treatment resistance within one year (secondary loss of response; SLR). Nonetheless, the etiologies of PNR and SLR are not clearly understood, and predictors of response to biologic agents are also not defined yet. Numerous studies are being performed to discover prediction markers of the response to biologic agents, and this review will introduce currently available therapeutic options for IBD, biologics under investigation, and recent studies exploring various predictive factors related to PNR and SLR.

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.

Treatment Outcomes of Patients with Multidrug-Resistant Tuberculosis: Comparison of Pre- and Post-Public-Private Mix Periods.

BACKGROUND: This study compared the treatment outcomes of patients with multidrug-resistant tuberculosis (MDR-TB) before and after the implementation of public-private mix (PPM). Factors affecting treatment success were also investigated. METHODS: Data from culture-confirmed pulmonary MDR-TB patients who commenced MDR-TB treatment at Pusan National University Hospital between January 2003 and December 2017 were retrospectively reviewed. Patients were divided into two groups in terms of PPM status: pre-PPM period, patients who commenced MDR-TB treatment between 2003 and 2010; and post-PPM period, patients treated between 2011 and 2017. RESULTS: A total of 176 patients were included (64 and 112 in the pre- and post-PPM periods, respectively). 36.9% of the patients were resistant to a fluoroquinolone or a second-line injectable drug, or both. The overall treatment success rate was 72.7%. The success rate of post-PPM patients was higher than that of pre-PPM patients (79.5% vs. 60.9%, p=0.008). Also, loss to follow-up was lower in the post-PPM period (5.4% vs. 15.6%, p=0.023). In multivariate regression analysis, age ≥65 years, body mass index ≤18.5 kg/m2, previous TB treatment, bilateral lung involvement, and extensively drug-resistant (XDR)- or pre-XDR-TB were associated with poorer treatment outcomes. However, the use of bedaquiline or delamanid for ≥1 month increased the treatment success. CONCLUSION: The treatment success rate in MDR-TB patients was higher in the post-PPM period than in the pre-PPM period, particularly because of the low rate of loss to follow-up. To ensure comprehensive patient-centered PPM in South Korea, investment and other support must be adequate.

More than Nutrition: Therapeutic Potential of Breast Milk-Derived Exosomes in Cancer.

Human breast milk (HBM) is an irreplaceable source of nutrition for early infant growth and development. Breast-fed children are known to have a low prevalence and reduced risk of various diseases, such as necrotizing enterocolitis, gastroenteritis, acute lymphocytic leukemia, and acute myeloid leukemia. In recent years, HBM has been found to contain a microbiome, extracellular vesicles or exosomes, and microRNAs, as well as nutritional components and non-nutritional proteins, including immunoregulatory proteins, hormones, and growth factors. Especially, the milk-derived exosomes exert various physiological and therapeutic function in cell proliferation, inflammation, immunomodulation, and cancer, which are mainly attributed to their cargo molecules such as proteins and microRNAs. The exosomal miRNAs are protected from enzymatic digestion and acidic conditions, and play a critical role in immune regulation and cancer. In addition, the milk-derived exosomes are developed as drug carriers for delivering small molecules and siRNA to tumor sites. In this review, we examined the various components of HBM and their therapeutic potential, in particular of exosomes and microRNAs, towards cancer.