Safety, effectiveness, and usefulness of higher-dose tablets of generic pirfenidone in patients with IPF: a nationwide observational study in South Korea.

Background: Pirfenidone is an antifibrotic medication approved for idiopathic pulmonary fibrosis (IPF). Fybro®, a generic version of pirfenidone developed in South Korea, gained approval and is available in 200 mg and in higher-dose formulations of 400 and 600 mg. This real-world prospective cohort study investigated the safety and effectiveness of Fybro®. Methods: A nationwide observational study was conducted in patients with IPF. Patients were followed up for 6 months, with a subset of patients being followed up for 12 months. Data on lung function and adverse events were collected. Patient adherence to fewer-pill (400 and/or 600 mg tablets) and multiple-pill (200 mg tablets) regimens were compared. Results: Of the 359 enrolled patients, 352 received pirfenidone (Fybro®) at least once and were included in the analysis. The mean age was 69.0 years and 82.4% of patients were male. The median treatment duration was 186.0 days. A total of 253 patients (71.9%) experienced adverse events, with decreased appetite being the most common (16.5%). The adjusted decline rates in lung function were -1.5% and -2.2% predicted per year for forced vital capacity and diffusing capacity, respectively. No significant differences were observed based on the pirfenidone dose. For a daily intake of 1,200 or 1800 mg of pirfenidone, a significantly longer duration of drug administration was observed with the fewer-pill regimen than with multiple-pill regimen. Conclusion: The safety and effectiveness of Fybro® observed in this real-world cohort study are consistent with previous studies. Using higher-strength tablets to reduce pill burden may improve medication adherence.

Impact of residual microcalcifcations on prognosis after neoadjuvant chemotherapy in breast cancer patients.

BACKGROUND: Residual microcalcifications after neoadjuvant chemotherapy (NAC) are challenging for deciding extent of surgery and questionable for impact on prognosis. We investigated changes in the extent and patterns of microcalcifications before and after NAC and correlated them with pathologic response. We also compared prognosis of patients depending on presence of residual microcalcifications after NAC. METHODS: A total of 323 patients with invasive breast carcinoma treated with neoadjuvant chemotherapy at Kangbuk Samsung Hospital and Samsung Medical center from March 2015 to September 2018 were included. Patients were divided into four groups according to pathologic response and residual microcalcifications. Non-pCRw/mic group was defined as breast non-pCR with residual microcalcifications. Non-pCRw/o mic group was breast non-pCR without residual microcalcifications. pCRw/mic group was breast pCR with residual microcalcifications. pCRw/o mic group was breast pCR without residual microcalcifications. The first aim of this study is to investigate changes in the extent and patterns of microcalcifications before and after NAC and to correlate them with pathologic response. The second aim is to evaluate oncologic outcomes of residual microcalcifications according to pathologic response after NAC. RESULTS: There were no statistical differences in the extent, morphology, and distribution of microcalcifications according to pathologic response and subtype after NAC (all p > 0.05). With a median follow-up time of 71 months, compared to pCRw/o mic group, the hazard ratios (95% confidence intervals) for regional recurrence were 5.190 (1.160-23.190) in non-pCRw/mic group and 5.970 (1.840-19.380) in non-pCRw/o mic group. Compared to pCRw/o mic group, the hazard ratios (95% CI) for distant metastasis were 8.520 (2.130-34.090) in non-pCRw/mic group, 9.120 (2.850-29.200) in non-pCRw/o mic group. Compared to pCRw/o mic, the hazard ratio (95% CI) for distant metastasis in pCRw/mic group was 2.240 (0.230-21.500) without statistical significance (p = 0.486). CONCLUSIONS: Regardless of residual microcalcifications, patients who achieved pCR showed favorable long term outcome compared to non-pCR group.

Validation of a scoring system to predict bladder dysfunction after laparoscopic rectal cancer surgery.

PURPOSE: A recent trend in  urinary catheter management in patients who underwent laparoscopic rectal cancer surgery is early removal. However, some patients develop bladder dysfunction and require urinary re-catheterization. In 2016, a scoring system to predict bladder dysfunction after laparoscopic rectal cancer surgery was developed in our institution. The aim of this study was to demonstrate the validity of this scoring system and to determine the suitability of patients for early removal of urinary catheter. METHODS: A single-center, retrospective study from a prospective database was conducted on 234 patients who underwent elective laparoscopic rectal cancer surgery between January 2016 and December 2019. According to bladder dysfunction predictive score, the urinary catheter was removed on the first postoperative day (low-risk group) and fifth postoperative day (high-risk group). After catheter removal, all patients were managed using in-house protocols. RESULTS: Of 234 patients, 130 (55.6%) were classified as a low-risk group. The overall incidence of bladder dysfunction was 8.5% (11/130) in the low-risk group and 13.5% (14/104) in the high-risk group. CONCLUSION: The scoring system developed to predict bladder dysfunction showed good overall performance for discriminating between patients suitable or not for early removal of urinary catheter after laparoscopic rectal cancer surgery.

Assessment of Inhaler Satisfaction and Determinants of High Satisfaction Among Korean COPD Patients.

BACKGROUND: The Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines for chronic obstructive pulmonary disease (COPD) recommend considering patient preference when choosing an inhaler device. However, few studies have assessed both inhaler satisfaction and factors associated with high inhaler satisfaction. Therefore, we assessed inhaler satisfaction and determinants of high satisfaction in Korean COPD patients. METHODS: COPD patients were prospectively enrolled from January 2018 to November 2019. The 308 inhalers used by the 261 participants in this study included dry powder inhalers (Turbuhaler, Breezhaler, Ellipta, Diskus, and Genuair), a soft mist inhaler (Respimat), and pressurized metered dose inhalers (pMDIs). Inhaler satisfaction was assessed by the Feeling of Satisfaction with Inhaler (FSI-10) questionnaire. High inhaler satisfaction was defined as an FSI-10 ≥ 43. RESULTS: Among 261 COPD patients, 163 (62.5%) were highly satisfied with their inhaler device. The rates of high inhaler satisfaction for Turbuhaler, Breezhaler, Ellipta, Diskus, Genuair, Respimat, and pMDI usage were 40.0%, 67.2%, 66.7%, 50.0%, 55.6%, 63.4%, and 45.0%, respectively (P = 0.215). In univariate analyses, higher body mass index, non-current smoker, GOLD grades I and II, a modified Medical Research Council (mMRC) score < 2, lower inhaler puff burden, once daily usage of inhaler, and good inhaler adherence were associated with high inhaler satisfaction. In multivariate analyses, an mMRC score < 2, and good inhaler adherence were independently associated with high inhaler satisfaction. CONCLUSION: High inhaler satisfaction was associated with dyspnea symptom and good inhaler adherence in COPD patients. Effective strategies are needed including appropriate inhaler device selection, consideration of patient preference, and repeated inhaler education to improve patient satisfaction of inhalers.

Tissue Expansion after Non-Skin-Sparing Mastectomy: A Comparative Study of Expansion Courses of Prepectoral and Subpectoral Tissue Expander Placement with Acellular Dermal Matrix.

Although skin- or nipple-sparing mastectomy has been popular in the treatment of breast cancer, the radical excision of breast tissue is unavoidable in certain circumstances. However, the ability of an acellular dermal matrix (ADM) to expand remains questionable, and this situation may further hinder tissue expansion. From October 2017 to January 2020, patients who underwent immediate breast reconstruction with tissue expander placement using ADM whose initial fill volume was less than 50 mL were retrospectively reviewed. The primary outcomes were the number of visits and number of days required to complete the expansion, and the secondary outcomes were the amount of postoperative expansions, expander fill ratio and expander volume. Between the prepectoral group (n = 26) and subpectoral group (n = 39), the mean number of days (81.46 days versus 88.64 days, p = 0.365) and mean number of visits (5.08 versus 5.69, p = 0.91) required to complete expansion exhibited no significant differences. Additionally, there were no significant differences in the mean amount of postoperative expansion (314.23 mL versus 315.38 mL, p = 0.950), the mean final volume (353.08 mL versus 339.62 mL, p = 0.481) or the mean final volume ratio (0.89 versus 0.86, p = 0.35) between the two groups. Therefore, we suggest that prepectoral tissue expander placement after conventional mastectomy can be a valid option.

Association between skeletal muscle mass and mammographic breast density.

Mammographic density (MD) of the breast and body mass index (BMI) are inversely associated with each other, but have inconsistent associations with respect to the risk of breast cancer. Skeletal muscle mass index (SMI) has been considered to reflect a relatively accurate fat and muscle percentage in the body. So, we evaluated the relation between SMI and MD. A cross-sectional study was performed in 143,456 women who underwent comprehensive examinations from 2012 to 2016. BMI was adjusted to analyze whether SMI is an independent factor predicting dense breast. After adjustment for confounding factors including BMI, the odds ratios for MD for the dense breasts was between the highest and lowest quartiles of SMI at 2.65 for premenopausal women and at 2.39 for postmenopausal women. SMI was a significant predictor for MD, which could be due to the similar growth mechanism of the skeletal muscle and breast parenchymal tissue. Further studies are needed to understand the causal link between muscularity, MD and breast cancer risk.

Radial Probe Endobronchial Ultrasound Using Guide Sheath-Guided Transbronchial Lung Biopsy in Peripheral Pulmonary Lesions without Fluoroscopy.

BACKGROUND: Radial probe endobronchial ultrasound-guided transbronchial lung biopsy (RP-EBUS-TBLB) has improved the diagnostic yield of bronchoscopic biopsy of peripheral pulmonary lesions (PPLs). The diagnostic yield and complications of RP-EBUS-TBLB for PPLs vary depending on the technique, such as using a guide sheath (GS) or fluoroscopy. In this study, we investigated the utility of RP-EBUS-TBLB using a GS without fluoroscopy for diagnosing PPLs. METHODS: We retrospectively reviewed data from 607 patients who underwent RP-EBUS of PPLs from January 2019 to July 2020. TBLB was performed using RP-EBUS with a GS without fluoroscopy. The diagnostic yield and complications were assessed. Multivariable logistic regression analyses were used to identify factors affecting the diagnostic yields. RESULTS: The overall diagnostic accuracy was 76.1% (462/607). In multivariable analyses, the size of the lesion (≥20 mm; odds ratio [OR], 2.06; 95% confidence interval [CI], 1.27-3.33; p=0.003), positive bronchus sign in chest computed tomography (OR, 2.30; 95% CI, 1.40-3.78; p=0.001), a solid lesion (OR, 2.40; 95% CI, 1.31-4.41; p=0.005), and an EBUS image with the probe within the lesion (OR, 6.98; 95% CI, 4.38-11.12; p<0.001) were associated with diagnostic success. Pneumothorax occurred in 2.0% (12/607) of cases and chest tube insertion was required in 0.5% (3/607) of patients. CONCLUSION: RP-EBUS-TBLB using a GS without fluoroscopy is a highly accurate diagnostic method in diagnosing PPLs that does not involve radiation exposure and has acceptable complication rates.

Utility of Radial Probe Endobronchial Ultrasound Guided Transbronchial Lung Biopsy in Bronchus Sign Negative Peripheral Pulmonary Lesions.

BACKGROUND: The presence of the bronchus sign on chest computed tomography is associated with an increased diagnostic yield of radial probe endobronchial ultrasound-guided transbronchial lung biopsy (RP-EBUS-TBLB). However, the utility of RP-EBUS-TBLB for bronchus sign negative peripheral pulmonary lesions (PPLs) remains unknown. We investigated the utility of RP-EBUS-TBLB in bronchus sign negative PPLs. METHODS: We retrospectively reviewed data from 109 patients who underwent RP-EBUS for bronchus sign negative PPLs from January 2019 to August 2020. TBLB was performed using RP-EBUS with a guide sheath and without fluoroscopy. The EBUS visualization and TBLB diagnostic yields were assessed. Multivariable logistic regression analyses were used to identify factors affecting the EBUS visualization and diagnostic yields. RESULTS: The EBUS visualization yield was 74.1% (68/109). Of the 109 lung lesions, 92 were definitively diagnosed. The overall diagnostic accuracy, sensitivity, specificity, positive predictive value, and negative predictive value were 50.5% (55/109), 34.9% (29/83), 100% (26/26), 100% (29/29), and 32.5% (26/80), respectively. In multivariable analyses, the size of the lesion (≥ 20 mm; odds ratio [OR], 2.62; 95% confidence interval [CI], 1.16-5.93; P = 0.021) and the distance from the pleura (> 10 mm; OR, 2.37; 95% CI, 1.02-5.52; P = 0.045) were associated with EBUS visualization. Regarding diagnostic yield, having the probe within the lesion (OR, 28.50; 95% CI, 6.26-129.85; P < 0.001) and a solid lesion (OR, 14.58; 95% CI, 2.64-80.38; P = 0.002) were associated with diagnostic success. Pneumothorax and hemoptysis occurred in 3.7% (4/109) and 0.9% (1/109), respectively, of the patients. CONCLUSION: RP-EBUS-TBLB using a GS can be considered a diagnostic method in bronchus sign negative solid PPLs. Having the probe within the lesion and a solid lesion were important for diagnostic success. Complication rates were acceptable.

Clinical impact of blood pressure variability in patients with COVID-19 and hypertension.

OBJECTIVE: This study aimed to investigate the relationship between blood pressure variability (BPV) and clinical outcomes in patients with coronavirus disease 2019 (COVID-19) and hypertension. METHODS: A total of 136 patients hospitalized with COVID-19 were enrolled in this study. Patients were grouped according to the presence of hypertension and BPV. Mean arterial pressure (MAP) measured at 8 a.m. and 8 p.m. was analyzed, and BPV was calculated as the coefficient of variation of MAP (MAPCV). High BPV was defined as MAPCV values above the median. We compared the age, level of C-reactive protein (CRP), creatine kinase-MB (CK-MB), N-terminal pro-B type natriuretic peptide (NT-proBNP), creatinine and in-hospital mortality and investigated the relationship among the groups. RESULTS: COVID-19 patients with hypertension were older (70 ± 12 vs. 53 ± 17 years; P < 0.001), had higher levels of CRP (9.4 ± 9.2 vs. 5.3 ± 8.2 mg/dL; P = 0.009), MAPCV (11.4 ± 4.8 vs. 8.9 ± 3.2; P = 0.002), and higher in-hospital mortality (19.6% vs. 5.9%; P = 0.013) than those without hypertension. There was a proportional relationship between BPV and age, levels of CRP, CK-MB, NT-proBNP, creatinine and in-hospital mortality (all, P < 0.05). In Cox regression analysis, advanced age [≥80 years, hazard ratio (HR) 10.4, 95% confidence interval (CI) 2.264-47.772, P = 0.003] and higher MAPCV (HR 1.617, 95% CI, 1.281-2.040, P < 0.001) were significantly associated with in-hospital mortality. CONCLUSION: High BPV in COVID-19 patients with hypertension is significantly associated with in-hospital mortality. Advanced age and systemic inflammation are proportional to high BPV. Additional attention is needed for COVID-19 patients with hypertension and high BPV.

Comparative Study of Inhaler Device Handling Technique and Risk Factors for Critical Inhaler Errors in Korean COPD Patients.

OBJECTIVE: Critical inhaler handling errors are associated with an increased risk of adverse outcomes in patients with chronic obstructive pulmonary disease (COPD). However, real-world data on inhaler device handling techniques and the risk factors for critical inhaler errors in the Asian population have been examined in only a few studies. We evaluated the rates and risk factors for critical inhaler errors in the COPD population in Korea. METHODS: COPD patients were prospectively enrolled from January 2018 to November 2019. An advanced practice nurse evaluated their inhaler technique. The 308 inhalers used by the 261 participants in this study included dry powder inhalers (DPIs; Turbuhaler, Breezhaler, Ellipta, Diskus, Genuair), a soft mist inhaler (SMI; Respimat), and pressurized metered dose inhalers (pMDIs). RESULTS: The percentage critical errors for Turbuhaler, Breezhaler, Ellipta, Diskus, Genuair, Respimat, and pMDI usage were 60.0%, 41.0%, 27.8%, 12.5%, 44.4%, 45.5%, and 55.0%, respectively. In the multivariate analyses, female sex, short COPD duration, dissatisfaction with the inhaler (assessed by FSI-10), and moderate acute exacerbations (AEs) in the prior year were independent risk factors for any critical error in the DPI group. In the SMI group, a low education level and frequent AEs in the prior year were independent risk factors for any critical error, whereas a high COPD assessment test (CAT) score was the only risk factor in the pMDI group. CONCLUSION: Critical inhaler errors are common among patients with COPD, regardless of their preferred inhaler device. The rates and risk factors for critical inhaler errors differed among patients using different devices. Optimal device selection considering the risk factors of inhaler misusage will improve disease control in COPD patients.

Efficacy and safety of single-inhaler extrafine triple therapy versus inhaled corticosteroid plus long-acting beta2 agonist in eastern Asian patients with COPD: the TRIVERSYTI randomised controlled trial.

BACKGROUND: A single-inhaler extrafine triple combination of beclometasone dipropionate (BDP), formoterol fumarate (FF) and glycopyrronium (G) has been developed for maintenance therapy of chronic obstructive pulmonary disease (COPD). This study evaluated the efficacy and safety of BDP/FF/G in patients in three eastern Asian areas: China, Republic of Korea and Taiwan. METHODS: TRIVERSYTI was a double-blind, randomised, active-controlled, parallel-group study in patients with COPD, post-bronchodilator forced expiratory volume in 1 s (FEV1) < 50% predicted, ≥ 1 exacerbation in the previous 12 months, and receiving inhaled maintenance medication. Patients received either extrafine BDP/FF/G 100/6/10 µg via pressurised metered-dose inhaler, or non-extrafine budesonide/formoterol (BUD/FF) 160/4.5 µg via dry-powder inhaler, both administered as two puffs twice-daily for 24 weeks. The co-primary objectives (analysed in the overall population) were to demonstrate superiority of BDP/FF/G over BUD/FF for change from baseline in pre-dose morning and 2-h post-dose FEV1 at Week 24 (these were analysed as key secondary objectives in the China subgroup). The rate of moderate/severe COPD exacerbations was a secondary endpoint. RESULTS: Of 708 patients randomised, 88.8% completed. BDP/FF/G was superior to BUD/FF for pre-dose and 2-h post-dose FEV1 at Week 24 [adjusted mean differences 62 (95% CI 38, 85) mL and 113 (87, 140) mL; both p < 0.001]. The annualised moderate/severe exacerbation rate was 43% lower with BDP/FF/G [rate ratio 0.57 (95% CI 0.42, 0.77); p < 0.001]. Adverse events were reported by 61.1% and 67.0% patients with BDP/FF/G and BUD/FF. Results were similar in the China subgroup. CONCLUSIONS: In patients with COPD, FEV1 < 50% and an exacerbation history despite maintenance therapy, treatment with extrafine BDP/FF/G improved bronchodilation, and was more effective at preventing moderate/severe COPD exacerbations than BUD/FF. Trial registration CFDA CTR20160507 (registered 7 Nov 2016, http://www.chinadrugtrials.org.cn/index.html ).

The effects of repeated inhaler device handling education in COPD patients: a prospective cohort study.

Inhaler education for chronic obstructive pulmonary disease (COPD) patients improves inhaler technique and adherence. However, the effects of such education on the quality of life and inhaler satisfaction remain unclear. Here, we evaluated inhaler handling and adherence, and changes in quality of life and inhaler satisfaction, after repeated education for COPD patients. We prospectively enrolled COPD patients who had used inhalers for over 1 month and evaluated the effects of repeated education. Three visits were made over 6 months; an advanced practice nurse evaluated inhaler technique and adherence, and instructed the patients in inhaler technique during face-to-face sessions. Inhaler technique and adherence were assessed at every visits, and the modified Medical Research Council (mMRC) test, COPD Assessment Test (CAT), EuroQol-5D (EQ-5D), Patient Health Questionnaire (PHQ-9), and Feeling of Satisfaction with Inhaler questionnaire (FSI-10) were administered before (visit 1) and after two educational sessions (visit 3). A total of 261 COPD patients (308 inhalers) were included. Education significantly reduced the proportion of critical errors after two educational sessions (visit 3), from 43.2 to 8.8% (p < 0.001). The proportion of highly compliant patients increased after two visits, from 81.6% to 87.7% (p = 0.005). The FSI-10 score improved significantly after education, from 44.36 ± 4.69 to 47.64 ± 4.08 (p < 0.001); the scores on the other instruments (mMRC, CAT, EQ-5D, and PHQ-9) did not improve. Repeated face-to-face inhaler education by an advanced practice nurse significantly improved inhaler satisfaction, technique, and adherence. However, inhaler education did not significantly improve quality of life.

The Risk of Diabetes on Clinical Outcomes in Patients with Coronavirus Disease 2019: A Retrospective Cohort Study.

BACKGROUND: To determine the role of diabetes mellitus (DM) in the coronavirus disease 2019 (COVID-19), we explored the clinical characteristics of patients with DM and compared risk factors such as age, glycemic control, and medications to those without DM. METHODS: This was a retrospective cohort study of 117 confirmed patients with COVID-19 which conducted at a tertiary hospital in Daegu, South Korea. The primary outcome was defined as the severe and critical outcome (SCO), of which the composite outcomes of acute respiratory distress syndrome, septic shock, intensive care unit care, and 28-day mortality. We analyzed what clinical features and glycemic control-related factors affect the prognosis of COVID-19 in the DM group. RESULTS: After exclusion, 110 participants were finally included. DM patients (n=29) was older, and showed higher blood pressure compared to non-DM patients. DM group showed higher levels of inflammation-related biomarkers and severity score, and highly progressed to SCO. After adjustment with other risk factors, DM increased the risk of SCO (odds ratio [OR], 10.771; P<0.001). Among the DM patients, SCO was more prevalent in elderly patients of ≥70 years old and age was an independent risk factor for SCO in patients with DM (OR, 1.175; P=0.014), while glycemic control was not. The use of medication did not affect the SCO, but the renin-angiotensin system inhibitors showed protective effects against acute cardiac injury (OR, 0.048; P=0.045). CONCLUSION: The COVID-19 patients with DM had higher severity and resulted in SCO. Intensive and aggressive monitoring of COVID-19 clinical outcomes in DM group, especially in elderly patients is warranted.

Clinical Features and Outcomes of 98 Patients Hospitalized with SARS-CoV-2 Infection in Daegu, South Korea: A Brief Descriptive Study.

Although some information on the epidemiology of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and a few selected cases has been reported, data on the clinical characteristics and outcomes of patients hospitalized therewith in South Korea are lacking. We conducted a retrospective single-center study of 98 consecutive hospitalized patients with confirmed SARS-CoV-2 infection at Yeungnam University Medical Center in Daegu, South Korea. Sixty patients were women (61.2%), and the mean age was 55.4±17.1 years. Thirteen patients (13.3%) were treated in the intensive care unit (ICU). The mean interval from symptom onset to hospitalization was 7.7±4.5 days. Patients who received ICU care were significantly older and were more likely to have diabetes mellitus. The National Early Warning Score on the day of admission was significantly higher in patients requiring ICU care. Acute respiratory distress syndrome (13/13 patients; 100%), septic shock (9/13; 69.2%), acute cardiac injury (9/13; 69.2%), and acute kidney injury (8/13; 61.5%) were more common in patients who received ICU care. All patients received antibiotic therapy, and most (97/98 patients; 99.0%) received antiviral therapy (lopinavir/ritonavir). Hydroxychloroquine was used in 79 patients (80.6%), and glucocorticoid therapy was used in 18 patients (18.4%). In complete blood counts, lymphopenia was the most common finding (40/98 patients; 40.8%). Levels of all proinflammatory cytokines were significantly higher in ICU patients. As of March 29, 2020, the mortality rate was 5.1%. Here, we report the clinical characteristics and laboratory findings of SARS-CoV-2 patients in South Korea up to March 29, 2020.

Comprehensive Effects of Organized Education for Patients with Chronic Obstructive Pulmonary Disease.

Background: Despite the increasing prevalence of chronic obstructive pulmonary disease (COPD) worldwide, knowledge and awareness of COPD remain extremely low. This prospective study aimed to demonstrate the effectiveness of organized educational intervention. Patients and methods: The study participants included patients diagnosed with COPD and receiving inhaler treatment. In this prospective study, the patients made three sequential visits to the hospital (baseline, 1 month, 3 months). On their first and second visits, patients received systematic education about COPD. On their first and third visits, each patient was evaluated using a COPD Assessment Test, COPD Knowledge Questionnaire, Hospital Anxiety and Depression Scale, and Rosenberg Self-Esteem Scale. Results: Fifty-five participants were enrolled in the study. The mean COPD knowledge score before and after education was 12.51±3.19 and 17.89±1.37, respectively, indicating a significant increase in the score post-education (P<0.001). The measure of patients' inhaler technique also significantly improved after education (5.40±1.50 vs 6.83±0.37 P=0.01). The rate of depression and anxiety after education decreased by 10.9% and 12.7%, respectively (P<0.001). In subgroup analysis, we compared the groups whose knowledge score increased by more than 5 points (Group B) and those whose score did not improve (Group A). In Group B, the mean CAT score significantly improved (2.61±5.88 vs -2.41±7.48, P=0.01), and the duration of their COPD diagnosis before enrollment was significantly shorter (2.72±2.43 vs 5.22±5.11 years, P=0.038) compared to those in Group A. Conclusion: An organized educational program resulted in improved disease-specific knowledge. Disease-specific education is an important part of the treatment of COPD that affects the quality of life and emotional status of patients. Early education after COPD diagnosis can be beneficial.

Critical Inhaler Handling Error Is an Independent Risk Factor for Frequent Exacerbations of Chronic Obstructive Pulmonary Disease: Interim Results of a Single Center Prospective Study.

Objective: Chronic obstructive pulmonary disease (COPD) acute exacerbations are significant causes of morbidity and mortality. "Frequent exacerbator" phenotypes are considered a distinct subgroup and this phenotype has a negative effect on lung function, quality of life, activity, hospital admission, and mortality. We assess inhaler handling technique and adherence, and evaluate risk factors associated with frequent exacerbations in COPD patients. Methods: This study was a cross-sectional, case-control study. We prospectively enrolled 189 COPD patients from Yeungnam University Hospital from January 2018 to November 2018. Subjects were tested regarding their inhaler technique in face-to-face interviews with an advanced practice nurse of inhaler upon study entry. Frequency of moderate to severe COPD exacerbations were reviewed via electronic medical records during 12 months prior to study entry. Frequent exacerbations were defined as ≥2 moderate to severe exacerbations in the prior 12 months. Multivariate logistic regression was performed to identify risk factors for frequent exacerbations. Results: Among 189 COPD patients, 50 (26.5%) were frequent exacerbators. Based on univariate analyses, body mass index (BMI) < 25 kg/m2, lower forced expiratory volume in 1 s (FEV1), higher mMRC, lower feeling of satisfaction with the inhaler, and any critical errors were potential risk factors for frequent exacerbations. Multivariate logistic regression analyses revealed that BMI < 25 kg/m2 (OR, 2.855, 95% CI, 1.247-6.534; p=0.013), higher mMRC (OR, 1.625, 95% CI, 1.072-2.463; p=0.022), and any critical error (OR, 2.020, 95% CI, 1.021-3.999; p=0.044) were risk factors. Conclusion: Any critical error, BMI < 25 kg/m2 and high mMRC are independent risk factors for frequent exacerbations in COPD patients. Careful monitoring and education around inhaler devices, particularly in frequent exacerbators, are important components of COPD treatment.

Predictive factors for the presence of invasive components in patients diagnosed with ductal carcinoma in situ based on preoperative biopsy.

BACKGROUND: In patients diagnosed with ductal carcinoma in situ (DCIS) with needle biopsy before surgery, invasive component (IC) is often found in the postoperative tissue, which results in altered post-surgical care. However, there are no clinically available factors to predict IC, and few MRI studies are available for the detection of IC in DCIS patients. The purpose of this study was to evaluate which risk factors can predict IC preoperatively. METHODS: Patients with a DCIS diagnosis based on preoperative biopsy, who underwent breast surgery Kangbuk Samsung Hospital between Jan 2005 and June 2018, were retrospectively evaluated. Clinico-pathological and breast MRI factors were compared between DCIS and DCIS with IC in postsurgical specimens. RESULTS: Of the 431 patients with a preoperative diagnosis of DCIS, 34 (7.9%) showed IC during the postoperative pathological investigations, and 217 (50.3%) underwent breast MRI. Among MRI-related factors, Mass-like enhancement on MRI was the sole but significant predictor of IC (HR = 0.26, C.I. = 0.07-0.93, p = 0.038), while nipple-areolar complex invasion, enhancement peak and pattern were not statistically significant. Nuclear grade was the only significant predictor of IC in the analysis of other clinico-pathological factors (HR = 2.39, C.I. = 1.05-5.42, p = 0.038 in univariate analysis, HR = 2.86, C.I. = 1.14-7.14, p = 0.025 in multivariate analysis). CONCLUSIONS: Mass-like enhancement on MRI and high nuclear grade were associated with IC in patients with preoperative diagnosis of DCIS. Considering the high sensitivity of breast MRI for IC, further evaluation of the predictive value of MRI in preoperative DCIS patients is desirable.

Serum concentration of thyroid hormones in abnormal and euthyroid ranges and breast cancer risk: A cohort study.

The impact of variations in serum thyroid hormone concentration within the euthyroid range on breast cancer risk remains unclear. We investigated the effect of serum thyrotropin (TSH) and thyroid hormone concentration on breast cancer risk. This cohort study involved 62,546 Korean women, aged ≥40 years, who were free of breast cancer at baseline and underwent health examination with determination of free thyroxine (FT4) and TSH. A parametric proportional hazard model was used to estimate the adjusted hazard ratio (aHR) and 95% confidence interval (CI). During a median follow-up of 4.8 years (interquartile range: 2.8-7.3 years), 834 incident breast cancers were identified. Compared to normal FT4 level, abnormally high serum FT4 level was associated with an increased risk of incident breast cancer with a corresponding multivariable aHR (95% CI) of 1.98 (1.02-3.83). This association tended to be stronger in postmenopausal women than in premenopausal women. Within the euthyroid range, the highest TSH tertile was associated with a lower risk of breast cancer than the lowest TSH tertile with a corresponding aHR (95% CI) of 0.68 (0.55-0.84). In contrast, highest FT4 tertile was associated with a higher risk of breast cancer than the lowest FT4 tertile. Abnormally high FT4 as well as higher FT4 within the euthyroid range were positively associated with breast cancer risk, while higher TSH concentration within the euthyroid range was negatively associated with breast cancer risk. Our findings indicate that thyroid function within both the abnormal and euthyroid ranges may contribute to the development of breast cancer.

Different prognostic values of individual hematologic parameters in papillary thyroid cancer due to age-related changes in immunity.

PURPOSE: Several studies have reported the plausible association of neutrophil-to-lymphocyte ratio (NLR) with the prognosis of papillary thyroid cancer (PTC), but the results are inconsistent. In PTC, chronic inflammation is closely related to tumor progression, and the age of the patient has a great influence on prognosis. Therefore, considering the changes in the immune system with aging, we classified the patients according to age and assessed the prognostic value of individual hematologic parameters. METHODS: This retrospective analysis included 1,921 patients who underwent thyroidectomy for PTC. Patients were divided into 2 groups based on their age: Y-group (age < 45) and O-group (age ≥ 45). Blood counts were measured within 14 days before surgery. RESULTS: The Y-group consisted of 914 patients aged < 45 years and the O-group consisted of 932 patients aged ≥ 45. In both groups, the common prognostic factors related to disease recurrence were only 6 or more metastatic lymph node and grossly extrathyroidal extension, and hematologic parameters were different between the 2 groups. High Platelet-lymphocyte ratio (PLR) in the Y-group and high NLR in the O-group were identified as independent predictors of disease recurrence (NLR: hazard ratio [HR], 3.28; 95% confidence interval [CI], 1.23-8.73; P = 0.018; PLR: HR, 3.08; 95% CI, 1.26-7.52; P = 0.014). CONCLUSION: The results suggest that changes in immunity with aging may affect prognosis in patients with PTC, and thus hematologic parameters might be employed as prognostic markers depending on the age of the patients.

The prognostic and predictive value of tumor-infiltrating lymphocytes and hematologic parameters in patients with breast cancer.

BACKGROUND: Carcinogenesis and tumor growth are associated with chronic inflammation and the host immune system. Here, we investigated the clinical significance and relationship between tumor-infiltrating lymphocytes (TILs) and hematologic parameters in patients with breast cancer. METHODS: Invasive ductal breast cancer patients (N = 145) who underwent surgery were retrospectively evaluated. Samples were obtained using a core needle biopsy for CD8+, FOXP3+ TIL assessment. Blood lymphocytes, neutrophils, monocytes, and platelets were obtained by peripheral venous punctures. RESULTS: CD8 + TILs were significantly associated with absolute lymphocyte count (ALC) and the absolute monocyte count (AMC). Low LMR (ALC/AMC) (cut-off - 5.3, range = 0.73-12.31) was associated with poor overall survival (OS) (p = 0.010), disease-free survival (DFS) (p = 0.005). However, in subgroup analysis, LMR did not have any value as a prognostic factor in HER2-positive breast cancers. TILs had different prognostic impacts across breast cancer subtypes, although they were not statistically significant. The treatment response after NAC tended to improve in breast cancer patients with high FOXP3+ TILs, low NLR (neutrophil count/ALC) (FOXP3 p for trend = 0.006, NLR p for trend = 0.063). CONCLUSIONS: A relevance between TILs and hematologic parameters in breast cancer was demonstrated. The influence of the immune system on breast cancer progression may differ by subtype.