Expression of CD163 and major histocompatibility complex class I as diagnostic markers for idiopathic inflammatory myopathies.

BACKGROUND: To develop an inflammation-related immunohistochemistry marker-based algorithm that confers higher diagnostic ability for idiopathic inflammatory myopathies (IIMs) than IIM-related histopathologic features. METHODS: Muscle biopsy tissues from 129 IIM patients who met the 2017 EULAR/ACR criteria and 73 control tissues from patients with non-inflammatory myopathies or healthy muscle specimens were evaluated for histological features and immunostaining results of CD3, CD4, CD8, CD20, CD68, CD163, MX1, MHC class I, MHC class II, and HLA-DR. Diagnostic algorithms for IIM were developed based on the results of the classification and regression tree (CART) analysis, which used immunostaining results as predictor variables for classifying patients with IIMs. RESULTS: In the analysis set (IIM, n = 129; control, n = 73), IIM-related histopathologic features had a diagnostic accuracy of 87.6% (sensitivity 80.6%; specificity 100.0%) for IIMs. Notably, muscular expression of CD163 (99.2% vs. 20.8%, p < 0.001) and MHC class I (87.6% vs. 23.1%, p < 0.001) was significantly higher in the IIM group than in controls. Based on the CART analysis results, we developed an algorithm combining CD163 and MHC class I expression that conferred a diagnostic accuracy of 95.5% (sensitivity 96.1%; specificity 94.5%). In addition, our algorithm was able to correctly diagnose IIM in 94.1% (16/17) of patients who did not meet the 2017 EUALR/ACR criteria but were diagnosed as having IIMs by an expert physician. CONCLUSIONS: Combination of CD163 and MHC class I muscular expression may be useful in diagnosing IIMs.

Risk of Breast Cancer in Association with the Use of Second-generation Antipsychotics.

Objective: Previous studies regarding the relationship between the risk of breast cancer (BC) and antipsychotics use have reported inconsistent findings. Insufficient sample size and/or observation period may have hindered revealing the risk of BC associated with antipsychotics use. We aimed to investigate whether the use of second-generation antipsychotics (SGA) is associated with increased risk of BC. Methods: We used the Health Insurance Review Agency database in South Korea between 2008 and 2018. The index date was determined as the date of the first antipsychotic prescription. We selected women prescribed SGAs for more than 30 days within a year from the index date and age-matched controls, yielding 498,970 cases and 997,940 controls. The Cox proportional hazards regression model was used for estimating the risk. Results: The incidence rates of BC were 109.74 and 101.51 per 100,000 person-years in the case and control groups, respectively. There was an increased risk of BC in the case group (hazard ratio [HR] = 1.08, 95% confidence interval [CI] 1.04-1.13). There was a higher risk of BC in subjects prescribed with ≥ 10,000 mg of olanzapine equivalent dose (HR = 1.29, 95% CI 1.14-1.46) than those with < 10,000 mg (HR = 1.05, 95% CI 1.00-1.11). The increased risk of BC in the case group became significant after six years of the observation period (≥ 6 years: HR = 1.24, 95% CI 1.14-1.35, 3 to < 6 years: HR = 1.06, 95% CI 0.97-1.15, < 3 years: HR = 1.02, 95% CI 0.95-1.09). Conclusion: This study indicated that the use of SGAs is associated with increased risk of BC in a long-term relationship with a dose-response pattern.

Surgical treatment of facial blushing: Patient selection and operative technique (retrospective observational study).

Surgeons are often reluctant to offer further intervention to patients with medically intractable facial blushing. This is mainly because of the relatively high failure rate of blushing resolution and a high incidence of compensatory hyperhidrosis. In this study, we sought to identify the type of blushing that would benefit from surgery and minimize compensatory hyperhidrosis by applying diffuse sympathicotomy (DS). This study was a retrospective review of 62 patients who underwent R2 endoscopic thoracic sympathicotomy (ETS) and preemptive DS for facial blushing. Facial blushing was classified as autonomic-mediated blushing (thermoregulatory, emotional) and vasodilator-mediated blushing (constant) based on the history and precipitating factors for blushing. DS was performed at lower-thoracic levels in the form of limited DS (right R5/7/9/11, left R5/6/8/10) or extended DS (bilateral R5-11). Resolution of blushing (described as "almost disappeared") was achieved in 48% of patients with a median follow-up of 19.6 months. There was a significant difference in resolution among 3 types of blushing (emotional: 55%, thermoregulatory: 28%, constant: 15%, P = .03). Multivariate analysis confirmed thermoregulatory and constant type blushing as a potential independent predictor of blushing resolution. Even though there was no difference between the DS procedures with respect to compensatory hyperhidrosis, intolerable compensatory hyperhidrosis (Hyperhidrosis Disease Severity Scale = 4) occurred in only 11% of patients. DS redistributed sweating area, being predominantly on the chest and mid-back (89%), also seen on the abdomen-waist-groin-buttocks-thighs (63%). Overall, 77% of patients experienced satisfactory results. Emotional blushing proved to be an established indication of ETS where good long-term results can be expected. Expansion of surgical indication to thermoregulatory or constant type blushing needs to be validated in future studies. Additionally, compensatory hyperhidrosis, another hurdle for ETS, can be minimized by preemptive DS, resulting in redistribution and decrease of sweating.

Comparative effectiveness of antipsychotic monotherapy and polypharmacy in schizophrenia patients with clozapine treatment: A nationwide, health insurance data-based study.

Clozapine is the most effective antipsychotic for treatment-resistant schizophrenia (TRS). However, it remains uncertain whether antipsychotic augmentation to clozapine has the superior effectiveness over clozapine alone and the effect size of clozapine compared to other antipsychotic drugs in TRS. Therefore, we examined the comparative effectiveness of antipsychotic monotherapy and polypharmacy on the risk of psychiatric admission and treatment discontinuation in TRS. Data were collected from the Health Insurance Review Agency database between January 2010 and December 2019 in South Korea. Among prevalent patients with schizophrenia, we defined 22,327 patients with TRS as those who had been prescribed with clozapine at least once during the entire observation period. Stratified Cox proportional hazards regressions were performed using data on all antipsychotic prescriptions of patients with TRS to investigate the risk of psychiatric hospitalization and treatment discontinuation associated with antipsychotic treatment. In individual comparisons, clozapine monotherapy was the most effective for the risk of psychiatric hospitalization compared to no use (hazard ratio [HR] = 0.23, 95% confidence interval [CI] = 0.22-0.25). In group comparisons, clozapine with long-acting injectable (LAI) second-generation antipsychotics (SGA) was superior to clozapine monotherapy for the risk of psychiatric hospitalization (HR = 0.60, 95%CI = 0.41-0.88). Clozapine monotherapy was associated with the lowest risk of treatment discontinuation in the individual and group comparisons. This retrospective observational population-based study reports that clozapine with LAI SGA is more effective in lowering the risk of psychiatric hospitalization in antipsychotic group comparison with the reference of clozapine monotherapy.

Diagnostic conversion from unipolar to bipolar affective disorder-A population-based study.

OBJECTIVES: It is essential to clinically distinguish bipolar affective disorder from unipolar affective disorders. However, patients previously diagnosed with unipolar affective disorder are sometimes later diagnosed with bipolar affective disorder, known as diagnostic conversion. Here we investigated diagnostic conversion using data from a nationwide population-based register. METHODS: We obtained claims data from 2007 to 2020 in Korea's Health Insurance Review Agency database and identified a cohort of patients who were diagnosed with unipolar depression in 2009 without prior psychiatric diseases within the previous 2 years. We studied the rate of diagnostic conversion and risk factors, especially antidepressants. RESULTS: About 6.5% of patients underwent diagnostic conversion during the observation period. Younger age at disease onset and usage of antidepressants increased the relative risk for diagnostic conversion. Patients using serotonin-norepinephrine reuptake inhibitors (SNRI) showed more than twice the risk compared to no usage of antidepressant. LIMITATION: First, this study was based on the population-based register data. Thus, we defined the patient cohort diagnosed with unipolar depression with strict inclusion criteria. Second, the exposure time differed between different antidepressants. Third, we estimated the relative risk for diagnostic conversion compared to no use of antidepressants. Moreover, we could not rule out the potential influence of antidepressant polypharmacy. CONCLUSION: We confirmed diagnostic conversion in some patients and identified younger age or usage of antidepressants, especially SNRI, as risk factors. Because unipolar and bipolar affective disorders show different disease courses or prognoses and have different treatment strategies, clinicians should be mindful of diagnostic conversion.

Discovery of Lactoferrin as a Stimulant for hADSC-Derived EV Secretion and Proof of Enhancement of Resulting EVs through Skin Model.

Extracellular vesicles (EVs) are secreted from hADSCs in low concentrations, which makes it difficult to utilize them for the development of therapeutic products. To overcome the problem associated with low concentration, we proposed human lactoferrin (hLF) as a stimulant for the secretion of hADSC-derived EVs. hLF has been reported to upregulate intracellular Ca2+, which is known to be capable of increasing EV secretion. We cultured hADSCs in hLF-supplemented media and analyzed the changes in intracellular Ca2+ concentration. The characteristics of hADSC-derived EVs secreted by hLF stimulation were analyzed through their number, membrane protein markers, and the presence of hLFs to EVs. The function of hADSC-derived EVs was investigated through their effects on dermal fibroblasts. We found that hLF helped hADSCs effectively uptake Ca2+, resulting in an increase of EVs secretion by more than a factor of 4. The resulting EVs had enhanced proliferation and collagen synthesis effect on dermal fibroblasts when compared to the same number of hADSC-derived EVs secreted without hLF stimulation. The enhanced secretion of hADSC-derived EVs increased collagen synthesis through enhanced epidermal penetration, which resulted from increased EV numbers. In summary, we propose hLF to be a useful stimulant in increasing the secretion rate of hADSC-derived EVs.

Risk of progression of idiopathic pulmonary fibrosis to connective tissue disease: a long-term observational study in 527 patients.

OBJECTIVE: Connective tissue disease (CTD) might occur during the course of idiopathic pulmonary fibrosis (IPF). Clinical factors associated with CTD development in IPF patients have still not been identified. We investigated which antibodies have a significant association with the development of CTD during the clinical course of IPF. METHODS: We retrospectively reviewed the records of 527 patients with a first diagnosis of IPF between January 2007 and March 2014 and investigated the time to CTD development after IPF diagnosis in these patients. RESULTS: CTD developed in 15 patients at a median of 2.1 years (range 1.2-4.8) after IPF diagnosis. All patients had anti-neutrophil cytoplasmic antibodies (ANCA) or autoantibodies that met the serology criteria for interstitial pneumonia with autoimmune features (IPAF). Survival duration for IPF patients with progression to CTD was 5.3 (3.8, 6.7) years, which was significantly longer than for IPF patients without progression to CTD [2.9 (1.7, 4.8), p = 0.001]. Independent risk factors for CTD development in IPF patients included female gender [adjusted hazard ratio (HR) 5.319, p = 0.0082], titer of rheumatoid factor (RF; adjusted HR, 1.006; p = 0.022), titer of anti-citrullinated protein antibody (ACPA; adjusted HR, 1.009; p = 0.0011), and titer of myeloperoxidase (MPO)-ANCA (adjusted HR, 1.02; p < 0.0001). CONCLUSION: Progression to CTD is uncommon in IPF patients. However, a significant number of IPF patients with high titers of RF, ACPA, or MPO-ANCA progressed to CTD. RF, ACPA, and MPO-ANCA might be significantly associated with CTD development in IPF patients. Key Points • A significant number of IPF patients with high titers of RF, ACPA, or MPO-ANCA progressed to CTD. • IPF/UIP with high titers of RF, ACPA, or MPO-ANCA might be the initial clinical manifestation of CTD. • RF, ACPA, and MPO-ANCA may be significantly associated with the development of pulmonary fibrosis in patients with CTD.

Clinical significance of HER2 status in T1bN0 breast cancer: a nationwide study from the Korean Breast Cancer Society.

PURPOSE: The prognosis of patients with node-negative T1b tumors according to human epidermal growth factor receptor 2 (HER2) status is not known. This group of patients has not been studied in the available randomized trials. The objective of this study was to evaluate the survival of patients in a monoethnic group diagnosed with T1b lymph node-negative breast cancer depending on HER2 status. METHODS: We analyzed 3110 patients with T1bN0M0 breast cancer whose data were deposited into the Korean Breast Cancer Society Registry database between 2000 and 2009. Overall survival (OS) and breast cancer-specific survival (BCSS) were compared according to HER2 status. RESULTS: Among all patients, 494 (15.9%) had HER2-positive breast cancer. At a mean follow-up of 93 months, 108 deaths and 86 breast cancer-specific deaths were noted among all patients. There was no significant difference in OS between the HER2-negative and HER2-positive groups (p = 0.103). The same result was observed for BCSS. However, in the subgroup of estrogen receptor (ER)-positive women, HER2-negative patients had a better BCSS prognosis than HER2-positive patients (p = 0.025). Multivariate analysis also indicated a significant difference in BCSS in the ER-positive subgroup (HR 2.60; 95% CI 1.15-5.87; p = 0.021). CONCLUSION: This study analyzed a large nationwide and monoethnic cohort and found a significant difference only in BCSS in the ER-positive subgroup according to HER2 status. Anti-HER2 therapy may be considered in HER2-positive and ER-positive patients with small, node-negative breast cancer.

Costal Chondrocyte-Derived Pellet-Type Autologous Chondrocyte Implantation versus Microfracture for Repair of Articular Cartilage Defects: A Prospective Randomized Trial.

OBJECTIVE: To compare the efficacy and safety of costal chondrocyte-derived pellet-type autologous chondrocyte implantation (CCP-ACI) with microfracture (MFx) for repair of articular cartilage defects of the knee. DESIGN: Thirty subjects with an International Cartilage Repair Society (ICRS) grade 3 to 4 chondral defect (2-10 cm2 in area; ≤4 cm3 in volume) were randomized at a ratio of 2:1 (CCP-ACI:MFx). Twenty patients were allocated in the CCP-ACI group and 10 patients in the MFx group. CCP-ACI was performed by harvesting costal cartilage at least 4 weeks before surgery. Implantation was performed without any marrow stimulation. Efficacy and safety were assessed at weeks 8, 24, and 48 after surgery according to the magnetic resonance observation of cartilage repair tissue (MOCART) score and clinical outcomes. RESULTS: MOCART scores improved from baseline to 24 and 48 weeks postoperatively in both treatment groups. The improvement in MOCART scores in the CCP-ACI group was significantly greater than that in the MFx group at 24 and 48 weeks (39.1 vs 21.8 and 43.0 vs 24.8, respectively). The proportions of complete defect repair and complete integration were significantly higher in the CCP-ACI group than the MFx group at 48 weeks. Improvement in Lysholm score and KOOS subscores, including Function (Sports and Recreational Activity) and knee-related quality of life was significantly greater in the CCP-ACI group than the MFx group at 48 weeks (35.4 vs 31.5, 35.7 vs 28.5, and 27.9 vs 11.6, respectively). CONCLUSION: Treatment of cartilage defects with CCP-ACI yielded satisfactory cartilage tissue repair outcomes, with good structural integration with native cartilage tissue shown by magnetic resonance imaging at 24 and 48 weeks after surgery. LEVEL OF EVIDENCE: Level 1: Randomized controlled study.

Autoantibodies against Protein Phosphatase Magnesium-Dependent 1A as a Biomarker for Predicting Radiographic Progression in Ankylosing Spondylitis Treated with Anti-Tumor Necrosis Factor Agents.

BACKGROUND: Patients with ankylosing spondylitis (AS) have increased levels of protein phosphatase magnesium-dependent 1A (PPM1A) and autoantibodies. We evaluated the usefulness of serum anti-PPM1A antibodies as a biomarker for AS. METHODS: Serum samples from 58 AS patients were obtained from a multicenter registry prior to the initiation of anti-TNF agents. The serum levels of anti-PPM1A antibodies were measured using ELISA. Spinal radiographic progression was defined as an increase in the modified stoke ankylosing spondylitis spinal score (mSASSS) by ≥2 units or a newly developed syndesmophyte. The role of exogenous PPM1A on bone mineralization was evaluated using primary osteoprogenitors acquired from patients with AS and non-inflammatory controls. RESULTS: The baseline levels of anti-PPM1A antibodies and mSASSS were higher in the radiographic progression group than in the non-progression group. In logistic regression analysis, baseline mSASSS and serum anti-PPM1A antibodies were associated with a higher risk of progression. The level of anti-PPM1A antibodies for predicting progression had an AUC of 0.716 (cut-off value: 43.77 ng/mL). PPM1A stimulation increased matrix mineralization in AS-osteoprogenitors but not in controls. CONCLUSION: Along with mSASSS, the serum levels of anti-PPM1A antibodies might be useful as a predictor of radiographic progression after treatment with anti-TNF agents.

Surgical treatment of compensatory hyperhidrosis: Retrospective observational study.

Compensatory hyperhidrosis is a debilitating postoperative condition occurring in 30% to 90% of patients with primary hyperhidrosis. The most appropriate treatment for compensatory hyperhidrosis remains controversial.Between January 2018 and December 2019, 44 patients with intractable compensatory hyperhidrosis underwent diffuse sympathicotomy (DS). In the early study periods, DS was performed sparsely (limited DS) to avoid possible adverse effects (right R5/7/9/11, left R5/6/8/10). In the late study periods, levels of surgical interruption were further modified to maximize sympatholytic effects (extended DS; bilateral R5/6/7/8/9/10/11). Patients were followed up for symptom resolution. For objective evidence of improved hyperhidrosis, thermographic images were taken for 7 patients.Immediate resolution of compensatory hyperhidrosis was achieved in 81% of patients, as determined at the 1 to 2 week postoperative visit. With a median follow-up of 22.7 months, compensatory hyperhidrosis continued to be resolved in 46% (n = 20). Logistic regression analysis showed that persistent resolution of compensatory hyperhidrosis was independently predicted by extended DS (odds ratio, 25.67, 95% CI, 1.78-1047.6; P = .036). The presence of gender, BMI, isolated compensatory hyperhidrosis, distribution of sweating, prior operation type, reoperation interval, and same-day lumbar sympathectomy failed to gain statistical significance on maintaining persistent resolution of compensatory hyperhidrosis. No patients experienced surgery-related side effects. Thermographic images obtained before/after surgery in 10 patients showed successful denervation and sweat diminishment.This study shows the safeness and effectiveness of DS for treating compensatory hyperhidrosis, representing a new treatment option. Future research should be directed at confirming a promising result of extended DS with further follow-up.

A N0 Predicting Model for Sentinel Lymph Node Biopsy Omission in Early Breast Cancer Upstaged From Ductal Carcinoma in Situ.

BACKGROUND: A prediction model with high sensitivity for the detection of negative axillary involvement can reduce additional axillary surgery in patients with ductal carcinoma in situ (DCIS) upstaged to invasive cancer while saving patients with pure DCIS from unnecessary axillary surgeries. Using a nationwide database, we developed and validated a scoring system for guidance in selective sentinel lymph node biopsy omission. PATIENTS AND METHODS: A total of 41,895 patients with clinically node-negative breast cancer from the Korean Breast Cancer Registry were included. The study cohort was randomly divided for the development and validation of the prediction model. Missing data were filled in using multiple imputation. Factors that were significantly associated with axillary lymph node (ALN) metastasis in > 50% of datasets were included in the final prediction model. RESULTS: The frequency of ALN metastasis in the total cohort was 24.5%. After multivariable logistic regression analysis, variables that were associated with ALN metastasis were palpability, multifocality, location, size, histologic type, grade, lymphovascular invasion, hormone receptor expression, and Ki-67 level. A scoring system was developed using these factors. The areas under the receiver operating characteristic curve for the scoring system was 0.750 in both training and validating sets. The cutoff value for performing sentinel lymph node biopsy was determined as a score of 4 to obtain prediction sensitivity higher than 95%. CONCLUSIONS: A scoring system to predict the probability of ALN metastasis was developed and validated. The application of this system in the clinic may reduce unnecessary axillary surgeries in patients with DCIS and minimize additional axillary surgery for upstaged patients with invasive cancer.

Costal Chondrocyte-Derived Pellet-Type Autologous Chondrocyte Implantation for Treatment of Articular Cartilage Defect.

BACKGROUND: Because articular chondrocyte-based autologous chondrocyte implantations (ACIs) have restrictively restored articular cartilage defects, alternative cell sources as a new therapeutic option for cartilage repair have been introduced. PURPOSE: To assess whether implantation of a costal chondrocyte-derived pellet-type (CCP) ACI allows safe, functional, and structural restoration of full-thickness cartilage defects in the knee. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: In this first-in-human study, 7 patients with symptomatic, full-thickness cartilage lesions were enrolled. The chondrocytes isolated from the patients' costal cartilage were expanded, followed by 3-dimensional pellet culture to prepare the CCP-ACI. Implantation of the pellets was performed via minimal arthrotomy and secured with a fibrin sealant. Clinical scores, including the International Knee Documentation Committee (IKDC) subjective, Lysholm, and Tegner activity scores, were estimated preoperatively and at 1, 2, and 5 years postoperatively. High-resolution magnetic resonance imaging was also performed to evaluate cartilage repair as well as to calculate the MOCART (magnetic resonance observation of cartilage repair tissue) score. RESULTS: The costal chondrocytes of all patients formed homogeneous-sized pellets, which showed the characteristics of the hyaline cartilaginous tissue with lacunae-occupied chondrocytes surrounded by glycosaminoglycan and type II collagen-rich extracellular matrix. There were no treatment-related serious adverse events during the 5-year follow-up period. Significant improvements were seen in all clinical scores from preoperative baseline to the 5-year follow-up (IKDC subjective score, 34.67 to 75.86; Lysholm score, 34.00 to 85.33; Tegner activity score, 1.17 to 4.67; and MOCART score, 28.33 to 83.33). Two patients had complete defect filling on magnetic resonance imaging evaluation at 1 year. Moreover, at 5 years postoperatively, complete defect filling was observed in 4 patients, and hypertrophy or incomplete defect filling (50%-100%) was observed in 2 patients. CONCLUSION: The overall results of this clinical study suggest that CCP-ACI can emerge as a promising therapeutic option for articular cartilage repair with good clinical outcomes and structural regeneration and with stable results at midterm follow-up. REGISTRATION: NCT03517046 ( ClinicalTrials.gov identifier).

Predictors Affecting Postoperative Atrial Fibrillation in Patients After Coronary Artery Bypass Graft.

The aim of this study is to investigate the differences in POAF (postoperative atrial fibrillation) and non-POAF patients using demographic and clinical characteristics and identify predictors affecting POAF after coronary artery bypass grafts in South Korea. This retrospective cohort study included 999 patients followed-up for at least 1 year after coronary artery bypass graft, between January 2011 and December 2015. Multivariate logistic regression was performed to assess risk factors based on demographics, as well as preoperative and postoperative characteristics. The adjusted multivariate analysis demonstrated that risk factors for POAF were old age (⩾65 years; odds ratio [OR] = 3.022, p < .001), ejection fraction less than 45% (OR = 1.489, p = .036), electrolyte potassium level after surgery (OR = 1.765, p = .003), and the average pain score on Postoperative Day 1 (OR = 1.253, p < .001). The incidence of atrial fibrillation after coronary artery bypass graft surgery can be reduced through the screening of preoperative risk factors, strict potassium monitoring, and pain management strategies.

CaSR-Mediated hBMSCs Activity Modulation: Additional Coupling Mechanism in Bone Remodeling Compartment.

Near the bone remodeling compartments (BRC), extracellular calcium concentration (Ca2+o) is locally elevated and bone marrow stromal cells (BMSCs) close to the BRC can be exposed to high calcium concentration. The calcium-sensing receptor (CaSR) is known to play a key role in maintaining extracellular calcium homeostasis by sensing fluctuations in the levels of extracellular calcium (Ca2+o). When human BMSCs (hBMSCs) were exposed to various calcium concentrations (1.8, 3, 5, 10, 30 mM), moderate-high extracellular calcium concentrations (3-5 mM) stimulated proliferation, while a high calcium concentration (30 mM) inhibited the proliferation. Exposure to various calcium concentrations did not induce significant differences in the apoptotic cell fraction. Evaluation of multi-lineage differentiation potential showed no significant difference among various calcium concentration groups, except for the high calcium concentration (30 mM) treated group, which resulted in increased calcification after in vitro osteogenic differentiation. Treatment of NPS2143, a CaSR inhibitor, abolished the stimulatory effect on hBMSCs proliferation and migration indicating that CaSR is involved. These results suggest that the calcium concentration gradient near the BRC may play an important role in bone remodeling by acting as an osteoblast-osteoclast coupling mechanism through CaSR.

Clinical significance of autoantibody positivity in idiopathic pulmonary fibrosis.

RATIONALE: The concept of interstitial pneumonia with autoimmune features (IPAF) was recently proposed by the American Thoracic Society. However, the clinical significance of the serologic domain of IPAF has not yet been established in idiopathic pulmonary fibrosis (IPF). OBJECTIVES: We aimed to investigate the clinical significance of autoantibody positivity in IPF. METHODS: We retrospectively reviewed the records of 512 patients diagnosed as IPF from January 2007 through March 2014. The patients were divided into two subgroups: (i) an autoantibody-positive IPF subgroup (n = 138), consisting of patients with anti-neutrophil cytoplasmic antibody (ANCA) or autoantibodies that met the criteria for the IPAF serologic domain; (ii) a lone IPF subgroup (n = 374), consisting of the rest of the IPF patients. MEASUREMENTS AND MAIN RESULTS: Autoantibody-positivity (HR 0.736, p = 0.043) was an independent risk factors for 5-year mortality on multivariable analysis in the overall IPF patients. In the autoantibody-positive IPF patients, use of glucocorticoid (not for management of acute exacerbation, HR 2.121, p = 0.019), use of immunomodulators (HR 0.310, p = 0.002), malignancy (HR 3.359, p = 0.002), baseline forced vital capacity (HR 0.974, p = 0.017), baseline diffusing capacity of the lung for carbon monoxide (HR 0.981, p = 0.041), and baseline 6-min walk test distance (HR 0.996, p = 0.002) were independent risk factors for 5-year mortality. CONCLUSIONS: Presence of ANCA or autoantibodies of the IPAF serologic domain in IPF patients is associated with better survival outcomes, and the use of immunomodulators is associated with superior survival outcomes.

Parity Differently Affects the Breast Cancer Specific Survival from Ductal Carcinoma In Situ to Invasive Cancer: A Registry-Based Retrospective Study from Korea.

PURPOSE: Multiparity might increase general mortality for women, but has inconclusive in patients with breast cancer. Here, we aim to discover their effect in terms of the breast cancer development hypothesis: from ductal carcinoma in situ to invasive carcinoma. METHODS: We included 37 947 patients from the web-based breast cancer registration program of the Korean Breast Cancer Society and analyzed survivals using multivariate Cox regression analysis and whether the associations of these factors displayed linear trends. They were divided into the following groups: (1) pure ductal carcinoma in situ (DCIS), (2) invasive ductal carcinoma (IDC) mixed with intraductal component (DCIS-IDC), and (3) node negative pure IDC. RESULTS: The mean age was 48.9 ± 9.9 years including premenopausal women was 61.8%. Although patients with parities of 1-3 had better prognosis compared with patients with nulliparous women, high parity (⩾4) increased the hazard ratio (HR) of overall survival (OS) (DCIS: HR, 1.52; 95% confidence interval [CI] 0.62-3.78; IDC: HR, 1.43, 95% CI 0.89-2.31; and DCIS-IDC: HR, 1.44, 95% CI 0.45-4.59) during 84.2 (±10.7) months. For breast cancer specific survival (BCSS), the HR of the IDC group (P-value for trend = .04) increased along with increasing parity and was worse than nulliparous patients, and the HR of the DCIS-IDC group increased but was better than nulliparous patients (P-value for trend = .02). Compared with nulliparous patients, any age at first birth (AFB) decreased HR of OS in the DCIS and IDC groups (DCIS: P = .01; IDC: P = .04). CONCLUSIONS: Parity show dual effects on OS of women with all ductal typed breast cancer but show different effects on BCSS in Korea.

Clinical subtypes and prognosis of pregnancy-associated breast cancer: results from the Korean Breast Cancer Society Registry database.

PURPOSE: We analyzed the clinicopathologic characteristics and prognosis of pregnancy-associated breast cancer (PABC) according to clinical subtypes to better understand the characteristics of PABC. METHODS: A total of 83,792 female patients between the ages of 20 and 49 were enrolled in the Korean Breast Cancer Society Registry database from January 1, 1996 to December 31, 2015. 'PABC' is defined as breast cancer diagnosed during pregnancy or within 1 year after delivery. Other patients were defined as 'non-PABC' patients. RESULTS: In non-PABC patients, luminal A subtype was the most common (50.2%). In PABC patients, TNBC was the most common (40.4%) subtype, while luminal A comprised 21.2% and HER2 subtype comprised 17.3%. There was a significant difference in overall survival (OS). In non-PABC patients, TNBC had the highest HR (HR 2.3, 95% CI 2.1-2.6). In PABC patients, the luminal B subtype (HR+ HER2-high Ki67) had the highest HR at 7.0 (95% CI 1.7-29.1). In multivariate analysis of OS by subtypes, PABC patients had significantly higher HR than non-PABC patients in the HER2 subtype (HR 2.0, 95% CI 1.1-3.7) and luminal B subtype (HR+ HER2-high Ki67) (HR 4.4, 95% CI 1.6-12.3). CONCLUSION: PABC showed different biologic features than non-PABC. PABC had a particularly poor prognosis in the luminal B (HR+ HER2-highKi67) and HER2 subtypes. To improve the prognosis of PABC, treatment should be considered according to subtype. Development of drugs that can be used during pregnancy is needed.

Feasibility of Percutaneous Dilatational Tracheostomy with a Light Source in the Surgical Intensive Care Unit.

BACKGROUND: Although percutaneous dilatational tracheostomy (PDT) under bronchoscopic guidance is feasible in the intensive care unit (ICU), it requires extensive equipment and specialists. The present study evaluated the feasibility of performing PDT with a light source in the surgical ICU. METHODS: The study involved a retrospective review of the outcomes of patients who underwent PDT with a light source performed by a surgery resident under the supervision of a surgical intensivist in the surgical ICU from October 2015 through September 2016. During the procedure, a light wand was inserted into the endotracheal tube after skin incision. Then, the light wand and the endotracheal tube were pulled out slightly, the passage of light through the airway was confirmed, and the relevant point was punctured. RESULTS: Fifty patients underwent PDT with a light source. The average procedural duration was 14.0 ± 7.0 minutes. There were no procedure-associated deaths. Intraoperative complications included minor bleeding in three patients (6%) and paratracheal placement of the tracheostomy tube in one patient (2%); these were immediately resolved by the surgical intensivist. Two patients required conversion to surgical tracheostomy because of the difficulty in light wand insertion into the endotracheal tube and a very narrow trachea, respectively. CONCLUSIONS: PDT with a light source can be performed without bronchoscopy and does not require expensive equipment and specialist intervention in the surgical ICU. It can be safely performed by a surgical intensivist with experience in surgical tracheostomy.

A Pathophysiological Validation of Collagenase II-Induced Biochemical Osteoarthritis Animal Model in Rabbit.

BACKGROUND: Current dilemma working with surgically-induced OA (osteoarthritis) model include inconsistent pathological state due to various influence from surrounding tissues. On the contrary, biochemical induction of OA using collagenase II has several advantageous points in a sense that it does not involve surgery to induce model and the extent of induced cartilage degeneration is almost uniform. However, concerns still exists because biochemical OA model induce abrupt destruction of cartilage tissues through enzymatic digestion in a short period of time, and this might accompany systemic inflammatory response, which is rather a trait of RA (rheumatoid arthritis) than being a trait of OA. METHODS: To clear the concern about the systemic inflammatory response that might be caused by abrupt destruction of cartilage tissue, OA was induced to only one leg of an animal and the other leg was examined to confirm the presence of systemic degenerative effect. RESULTS: Although the cartilage tissues were rapidly degenerated during short period of time upon biochemical induction of OA, they did not accompanied with RA-like process based on the histology data showing degeneration of articular cartilage occurred only in the collagenase-injected knee joint. Scoring evaluation data indicated that the cartilage tissues in non-induced joint remained intact. Neutrophil count transiently increase between day 8 and day 16, and there were no significant change in other complete blood count profile showing a characteristics of OA disease. CONCLUSION: These study shows that biochemically induced cartilage degeneration truly represented uniform and reliable OA state.