Exploration of MELK as a downstream of Del-1 and druggable targets in triple-negative breast cancer.

PURPOSE: In our previous study, Developmental endothelial locus-1 (Del-1) was a promising predictive marker for breast cancer. However, the downstream targets of Del-1 remain unknown. Here, we sought to discover a druggable target downstream of Del-1 and investigate the mechanism by which it regulates the course of breast cancer. METHODS: To investigate Del-1 downregulation effect on breast cancer, we performed transcriptome analysis using RNA sequencing of Del-1 knockdowned MDA-MB-231 cell line Plus, to investigate the expression of Del-1 and Maternal embryonic leucine zipper kinase (MELK), mRNA levels in eight different triple-Negative Breast Cancer (TNBC) cell lines were analyzed. High-throughput sequencing was performed on total RNA isolated. OTS167 was used for MELK inhibition. The effects of MELK on cell proliferation and invasion were determined using the MTT and Matrigel transwell assays. Furthermore, we examined MELK expression in breast cancer tissue. RESULTS: Del-1 and MELK mRNA expression levels were significantly higher in the TNBC cell lines, MDA-MB-468, HCC-1806, and MBA-MB-231. Knocking down Del-1 with siRNA in HCC-1806 and MBA-MB-231 cells significantly decreased MELK expression and thus suggested a possible relationship between Del-1 and MELK. In MDA-MB-468 cells, a basal-like 1 TNBC cell line, OTS167 significantly inhibited breast cancer cell proliferation and promoted cell apoptosis. To further investigate the relationship between Del-1 and MELK, dual inhibition of both Del-1 and MELK was performed, which significantly reduced the viability of MDA-MB-468 and MBA-MB-231 cells. CONCLUSION: We found that MELK acts downstream of Del-1 and is a promising druggable target, especially in basal-like and mesenchymal stem-like subtype.

Association between exposure to specific PM2.5 constituents and environment, lifestyle, and clinical parameters in patients with COPD.

This study investigated the correlation between the individual chemical constituents of particulate matter 2.5 µm (PM2.5) and respiratory parameters as well as the living environment and daily behaviors in patients with chronic obstructive pulmonary disease (COPD). Data were obtained from prospective COPD panel conducted in South Korea. Following collection via a microPEM, 18 metallic elements were determined using energy-dispersive X-ray fluorescence spectroscopy. All participants completed detailed questionnaires on living environments and lifestyle practices. Eighty-nine stable COPD patients (mean age 68.1 years; 94.4% male) were analyzed. Several constituents (titanium, aluminum, bromine, and silicone) were significantly associated with respiratory outcomes. Copper and manganese concentrations were significantly associated with the living environment. Increased ventilation time and air purifier operation were associated with lower concentrations of copper, silicone, barium, and titanium. These findings suggest varying relationships between PM2.5 constituents and clinical parameters in COPD patients, providing a basis for personalized interventions and future research.

Effects of gastroesophageal reflux disease treatment with proton pump inhibitors on the risk of acute exacerbation and pneumonia in patients with COPD.

BACKGROUND: Gastroesophageal reflux disease (GERD) has been suggested as a risk factor for acute exacerbation of chronic obstructive pulmonary disease (COPD). However, it remains undetermined whether proton pump inhibitor (PPI) treatment reduces the risk of exacerbation or affects the risk of pneumonia. This study aimed to evaluate the risks of both exacerbation and pneumonia following PPI treatment for GERD in patients with COPD. METHODS: This study used a reimbursement database of the Republic of Korea. Patients aged ≥ 40 years with COPD as a main diagnosis and who received PPI treatment for GERD at least for 14 consecutive days between January 2013 and December 2018 were included in the study. A self-controlled case series analysis was conducted to calculate the risk of moderate and severe exacerbation and pneumonia. RESULTS: A total of 104,439 patients with prevalent COPD received PPI treatment for GERD. The risk of moderate exacerbation was significantly lower during the PPI treatment than at baseline. The risk of severe exacerbation increased during the PPI treatment but significantly decreased in the post-treatment period. Pneumonia risk was not significantly increased during the PPI treatment. The results were similar in patients with incident COPD. CONCLUSIONS: The risk of exacerbation was significantly reduced after PPI treatment compared with the non-treated period. Severe exacerbation may increase due to uncontrolled GERD but subsequently decrease following PPI treatment. There was no evidence of an increased risk of pneumonia.

Glutamine increases stability of TPH1 mRNA via p38 mitogen-activated kinase in mouse mastocytoma cells.

Expression changes for tryptophan hydroxylase 1 (TPH1), the rate-limiting enzyme in serotonin synthesis, by environmental glutamine (GLN) were examined in mouse mastocytoma-derived P815-HTR cells. GLN-treated cells exhibited a robust increase in TPH1 mRNA after a 6 h exposure to GLN. 6-Diazo-5-oxo-L-norleucine (DON), a glutamine-utilizing glutaminase inhibitor, significantly inhibited the GLN-induction of TPH1 mRNA. Nuclear run-on assays and mRNA decay experiments demonstrated that the primary mechanism leading to increased TPH1 mRNA levels was not due to transcriptional changes, but rather due to increased TPH1 RNA stability induced by GLN. Treatment with GLN also led to activation of p38 MAP kinase, but not p42/44 MAPK. In addition, SB203580, a p38 MAP kinase specific inhibitor, completely abolished the GLN-mediated increase of TPH1 mRNA levels, suggesting the pathway stabilizing TPH1 mRNA might be mediated by the activated p38 MAP kinase pathway. Additionally, SB203580 significantly reduced the stability of TPH1 mRNA, and this reduction of the stability was not affected by GLN in the culture medium, implying a sequential signaling from GLN being mediated by p38 MAP kinase, resulting in alteration of TPH1 mRNA stability. TPH1 mRNA stability loss was also dependent on de novo protein synthesis as shown by treatment of cells with a transcriptional/translational blocker. We provide evidence that TPH1 mRNA levels are increased in response to increased exogenous GLN in mouse mastocytoma cells via a stabilization of TPH1 mRNA due to the activity of the p38 MAP kinase.

Risk adjustment model for tuberculosis compared to non-tuberculosis mycobacterium or latent tuberculosis infection: Center for Personalized Precision Medicine of Tuberculosis (cPMTb) cohort database.

BACKGROUND: The Center for Personalized Precision Medicine of Tuberculosis (cPMTb) was constructed to develop personalized pharmacotherapeutic systems for tuberculosis (TB). This study aimed to introduce the cPMTb cohort and compare the distinct characteristics of patients with TB, non-tuberculosis mycobacterium (NTM) infection, or latent TB infection (LTBI). We also determined the prevalence and specific traits of polymorphisms in N-acetyltransferase-2 (NAT2) and solute carrier organic anion transporter family member 1B1 (SLCO1B1) phenotypes using this prospective multinational cohort. METHODS: Until August 2021, 964, 167, and 95 patients with TB, NTM infection, and LTBI, respectively, were included. Clinical, laboratory, and radiographic data were collected. NAT2 and SLCO1B1 phenotypes were classified by genomic DNA analysis. RESULTS: Patients with TB were older, had lower body mass index (BMI), higher diabetes rate, and higher male proportion than patients with LTBI. Patients with NTM infection were older, had lower BMI, lower diabetes rate, higher previous TB history, and higher female proportion than patients with TB. Patients with TB had the lowest albumin levels, and the prevalence of the rapid, intermediate, and slow/ultra-slow acetylator phenotypes were 39.2%, 48.1%, and 12.7%, respectively. The prevalence of rapid, intermediate, and slow/ultra-slow acetylator phenotypes were 42.0%, 44.6%, and 13.3% for NTM infection, and 42.5%, 48.3%, and 9.1% for LTBI, respectively, which did not differ significantly from TB. The prevalence of the normal, intermediate, and lower transporter SLCO1B1 phenotypes in TB, NTM, and LTBI did not differ significantly; 74.9%, 22.7%, and 2.4% in TB; 72.0%, 26.1%, and 1.9% in NTM; and 80.7%, 19.3%, and 0% in LTBI, respectively. CONCLUSIONS: Understanding disease characteristics and identifying pharmacokinetic traits are fundamental steps in optimizing treatment. Further longitudinal data are required for personalized precision medicine. TRIAL REGISTRATION: This study registered ClinicalTrials.gov NO. NCT05280886.

Application of entire dental panorama image data in artificial intelligence model for age estimation.

BACKGROUND: Accurate age estimation is vital for clinical and forensic purposes. With the rapid advancement of artificial intelligence(AI) technologies, traditional methods relying on tooth development, while reliable, can be enhanced by leveraging deep learning, particularly neural networks. This study evaluated the efficiency of an AI model by applying the entire panoramic image for age estimation. The outcome performances were analyzed through supervised learning (SL) models. METHODS: Total of 27,877 dental panorama images from 5 to 90 years of age were classified by 2 types of grouping. In type 1 they were classified by each age and in type 2, applying heuristic grouping, the age over 20 years were classified by every 5 years. Wide ResNet (WRN) and DenseNet (DN) were used for supervised learning. In addition, the analysis with ± 3 years of deviation in both types were performed. RESULTS: For the DN model, while the type 1 grouping achieved an accuracy of 0.1016 and F1 score of 0.058, the type 2 achieved an accuracy of 0.3146 and F1 score of 0.2027. Incorporating ± 3years of deviation, the accuracy of type 1 and 2 were 0.281, 0.7323 respectively; and the F1 score were 0.1768, 0.6583 respectively. For the WRN model, while the type 1 grouping achieved an accuracy of 0.1041 and F1 score of 0.0599, the type 2 achieved an accuracy of 0.3182 and F1 score of 0.2071. Incorporating ± 3years of deviation, the accuracy of type 1 and 2 were 0.2716, 0.7323 respectively; and the F1 score were 0.1709, 0.6437 respectively. CONCLUSIONS: The application of entire panorama image data for supervised with classification by heuristics grouping with ± 3years of deviation for supervised learning models and demonstrated satisfactory outcome for the age estimation.

Comparing counseling outcome for college students: Metaverse and in-person approaches.

ABSTRACTObjective This study compared metaverse counseling with in-person counseling, using in-person counseling as a comparison group. To achieve this, we assessed whether metaverse counseling, a novel treatment approach, is comparable to traditional in-person counseling. Method: A total of 60 participants voluntarily participated in the study. Among the participants, 28 preferred in-person counseling, whereas 32 selected metaverse counseling as their preferred treatment option. Results and Conclusion: The findings indicated no statistically significant differences in the psychological symptom change patterns between the two counseling modalities. Both metaverse and in-person counseling demonstrated a common pattern of reduced symptom levels from pre-to post-session (Metaverse counseling Cohen's d = 1.04, In-person counseling Cohen's d = .62), which remained stable from post-session to follow-up regardless of the chosen counseling modality. Furthermore, the study revealed that the metaverse counseling group exhibited a higher level of working alliances than the in-person counseling group. Additionally, there was a slight tendency toward higher levels of counseling satisfaction in the metaverse counseling group than in the in-person counseling group. The results of this study support the use of synchronous metaverse programs to treat college students. The implications and limitations of this study are discussed. (195 words).

Pleuroparenchymal fibroelastosis in rheumatoid arthritis-associated interstitial lung disease.

BACKGROUND: Pleuroparenchymal fibroelastosis (PPFE) is a rare interstitial lung disease (ILD) featuring dense fibrosis of the visceral pleura and subpleural parenchyma, mostly in the upper lobes. PPFE can present in other ILDs, including rheumatoid arthritis-associated ILD (RA-ILD). The aim of this retrospective study was to investigate the prevalence and clinical implications of coexistent PPFE in RA-ILD. METHODS: Overall, 477 patients with RA-ILD were recruited from two cohorts; their clinical data and HRCT images were analysed. The criteria for diagnosing PPFE were (1) pleural thickening with bilateral subpleural dense fibrosis in the upper lobes, (2) evidence of disease progression, and (3) absence of other identifiable aetiologies. RESULTS: The median follow-up duration was 3.3 years. The mean age of the patients was 63.4 years, and 60.0% were women. PPFE was identified in 31 patients (6.5%). The PPFE group showed significantly lower body mass index and forced vital capacity (FVC) and more frequent usual interstitial pneumonia (UIP)-like pattern on HRCT than no-PPFE group. The risk factors for all-cause mortality were older age, lower FVC, and the presence of UIP-like pattern on HRCT; PPFE was not significantly associated with mortality in both all patients and a subgroup with a UIP-like pattern. The presence of PPFE was associated with a significantly increased risk of pneumothorax and greater decline in diffusing capacity. CONCLUSIONS: PPFE was not rare in patients with RA-ILD and was significantly associated with an increased risk of pneumothorax and greater lung function decline, though we found no significant association with mortality.

Diaphragmatic Dysfunction due to Neuralgic Amyotrophy After SARS-CoV-2 Vaccination: A Case Report.

Neuralgic amyotrophy is an idiopathic neuropathy characterized by acute-onset pain, typically in the upper extremity or shoulder, followed by weakness of the associated muscles. Phrenic nerve involvement is rare. We report a 63-year-old man who presented with dyspnea and right shoulder pain after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination. His chest radiograph showed an elevated right hemidiaphragm that was absent before vaccination. A pulmonary function test showed a restrictive pattern with a significant reduction (40%) in forced vital capacity in the supine position. Diaphragm ultrasonography revealed a reduction in both diaphragmatic excursion and a thickening fraction of the right hemidiaphragm. Electrophysiological studies suggested a right upper brachial plexopathy. Considering the temporal relationship between the vaccination and absence of other causes, SARS-CoV-2 vaccination was thought to be the reason for neuralgic amyotrophy with diaphragmatic dysfunction. As there was no evidence of hypoventilation or sleep disturbance that may require noninvasive ventilation, the patient was followed with conservative treatment with analgesics. During 8 months of follow-up, his shoulder pain was relieved significantly but dyspnea improved only slightly. Neuralgic amyotrophy is an under-diagnosed etiology of diaphragmatic dysfunction and should be considered in patients with dyspnea and shoulder pain.

Acute exacerbation of fibrotic hypersensitivity pneumonitis: incidence and outcomes.

BACKGROUND: Patients with fibrotic hypersensitivity pneumonitis (HP) show variable clinical courses, and some experience rapid deterioration (RD), including acute exacerbation (AE). However, little is known about AE in fibrotic HP. Here, we retrospectively examined the incidence, risk factors, and outcomes of AE in fibrotic HP. METHODS: The incidence rates of AE were calculated in 101 patients with biopsy-proven HP. AE was defined as the worsening of dyspnoea within 30 days, with new bilateral lung infiltration and no evidence of infection or other causes of dyspnoea. RESULTS: During follow-up (median: 30 months), 18 (17.8%) patients experienced AE. The 1, 3, and 5 year incidence rates of AE were 6.0, 13.6, and 22.8%, respectively. Lower diffusing capacity of the lung for carbon monoxide (DLCO) and a radiologic usual interstitial pneumonia (UIP)-like pattern were risk factors for AE. In-hospital mortality after AE was 44.4%. Median survival from diagnosis was significantly shorter in patients with AE (26.0 months) than in those with no-AE RD (55.0 months; p = 0.008) or no RD (not reached; p < 0.001). AE remained a significant predictor of all-cause mortality (hazard ratio, 8.641; 95% confidence interval, 3.388-22.040; p < 0.001) after adjustment for age, body mass index, lung function, lymphocyte levels in bronchoalveolar lavage fluid, and the presence of a UIP-like pattern. CONCLUSIONS: AE was not uncommon among patients with fibrotic HP and significantly affected prognosis. A lower DLCO value and radiologic UIP-like pattern at diagnosis were associated with the development AE in patients with fibrotic HP.

Dual versus monotherapy with bronchodilators in GOLD group B COPD patients according to baseline FEV1 level: a patient-level pooled analysis of phase-3 randomized clinical trials.

BACKGROUND: Which patients should receive dual therapy as initial treatment for chronic obstructive pulmonary disease (COPD) is only loosely defined. We evaluated if a lower forced expiratory volume in 1 s (FEV1) identifies a population more likely to benefit from dual therapy than monotherapy among group B COPD patients in whom Global initiative for Chronic Obstructive Pulmonary Disease (GOLD) recommends monotherapy as initial treatment. METHODS: This was a patient-level pooled analysis of phase-3 randomized controlled trials involving dual bronchodilators. Study patients were classified into two groups based on the FEV1 of 50% of the predicted value (GOLD I/II versus GOLD III/IV). We evaluated the efficacy of dual versus monotherapy (long-acting beta-2 agonist [LABA] or long-acting muscarinic antagonist [LAMA]) between these two groups in the following outcomes: changes in trough FEV1, the St. George's Respiratory Questionnaire (SGRQ) score, the proportion of SGRQ responders, time to first exacerbation, and risk of adverse events. RESULTS: A total of 14,449 group B patients from 12 studies were divided into GOLD III/IV (n = 8043) or GOLD I/II group (n = 6406). In the GOLD III/IV group, dual therapy was significantly more effective in improving FEV1, reducing SGRQ scores, and achieving a higher proportion of SGRQ responders compared with either LABA or LAMA. Dual therapy also showed a significantly longer time to first exacerbation compared with LABA in the GOLD III/IV group. In contrast, in the GOLD I/II group, the benefits of dual therapy over monotherapy were less consistent. Although dual therapy resulted in significantly higher FEV1 than either LABA or LAMA, it did not show significant differences in the SGRQ score and proportion of SGRQ responders as compared with LABA. The time to first exacerbation was also not significantly different between dual therapy and either LABA or LAMA in the GOLD I/II group. CONCLUSIONS: Dual therapy demonstrated benefits over monotherapy more consistently in patients with lower FEV1 than those with higher FEV1.

Characterization of the rabbit conjunctiva: Effects of sulfur mustard.

Sulfur mustard (SM; bis (2-chloroethyl) sulfide) is a potent vesicant which causes irritation of the conjunctiva and damage to the cornea. In the present studies, we characterized the ocular effects of SM in New Zealand white rabbits. Within one day of exposure to SM, edema and hazing of the cornea were observed, followed by neovascularization which persisted for at least 28 days. This was associated with upper and lower eyelid edema and conjunctival inflammation. The conjunctiva is composed of a proliferating epithelium largely consisting of stratified columnar epithelial cells overlying a well-defined dermis. Superficial layers of the conjunctival epithelium were found to express keratin 1, a marker of differentiating squamous epithelium, while in cells overlying the basement membrane expressed keratin 17, a marker of stratified squamous epithelium. SM exposure upregulated keratin 17 expression. Mucin 5 ac producing goblet cells were interspersed within the conjunctiva. These cells generated both acidic and neutral mucins. Increased numbers of goblet cells producing neutral mucins were evident after SM exposure; upregulation of expression of membrane-associated mucin 1 and mucin 4 in the superficial layers of the conjunctival epithelium were also noted. These data demonstrate that ocular exposure of rabbits to SM causes significant damage not only to the cornea, but to the eyelid and conjunctiva, suggesting multiple targets within the eye that should be assessed when evaluating the efficacy of potential countermeasures.

Prognostic Implication of Diagnostic Confidence Level in Patients with Fibrotic Hypersensitivity Pneumonitis.

BACKGROUND: Hypersensitivity pneumonitis (HP) has various clinical courses and outcomes, but the prognostic factors are not well-defined. Vasakova et al. [Am J Respir Crit Care Med. 2017 Sep;196(6):680-9] have proposed a diagnostic algorithm that categorized suspected patients according to the level of confidence in the diagnosis. This study aimed to investigate whether the confidence level of clinical diagnosis has prognostic implication in patients with fibrotic HP. METHODS: This study included 101 biopsy-proven fibrotic HP patients diagnosed between 2002 and 2017. The patients were retrospectively classified into confident, probable, possible, and unlikely chronic HP, according to the confidence level in the diagnostic criteria/algorithm. The survival and forced vital capacity (FVC) changes were compared between the groups. Risk factors for mortality were analysed using a Cox proportional hazard model. RESULTS: The median follow-up duration was 67.6 months. The mean age was 60.4 years, and percentages of women were 60.4%. When classified based on the diagnostic criteria/algorithm, possible HP was the most common (51.5%), followed by probable (26.7%), confident (9.9%), and unlikely HP (6.9%). Distinctive survival curves were found according to the diagnostic confidence level, showing the worst outcome in unlikely chronic HP (median survival, 30.2 months). In a multivariable Cox analysis, unlikely HP was a significant predictor of poor survival (hazard ratio, 4.652; 95% confidence interval, 1.231-17.586; p = 0.023), after adjustment for age, body mass index, FVC, and diffusing capacity. CONCLUSIONS: The diagnostic confidence level may predict clinical outcomes in patients with HP. Unlikely HP was shown to have a significantly poorer survival than other diagnostic confidence levels.

Azoxystrobin Impairs Neuronal Migration and Induces ROS Dependent Apoptosis in Cortical Neurons.

Fungicides often cause genotoxic stress and neurodevelopmental disorders such as autism (ASD). Fungicide-azoxystrobin (AZOX) showed acute and chronic toxicity to various organisms, and remained a concern for ill effects in developing neurons. We evaluated the neurotoxicity of AZOX in developing mouse brains, and observed prenatal exposure to AZOX reduced neuronal viability, neurite outgrowth, and cortical migration process in developing brains. The 50% inhibitory concentration (IC50) of AZOX for acute (24 h) and chronic (7 days) exposures were 30 and 10 µM, respectively. Loss in viability was due to the accumulation of reactive oxygen species (ROS), and inhibited neurite outgrowth was due to the deactivation of mTORC1 kinase activity. Pretreatment with ROS scavenger- N-acetylcysteine (NAC) reserved the viability loss and forced activation of mTORC1 kinase revived the neurite outgrowth in AZOX treated neurons. Intra-amniotic injection of AZOX coupled with in utero electroporation of GFP-labelled plasmid in E15.5 mouse was performed and 20 mg/kg AZOX inhibited radial neuronal migration. Moreover, the accumulation of mitochondria was significantly reduced in AZOX treated primary neurons, indicative of mitochondrial deactivation and induction of apoptosis, which was quantified by Bcl2/Bax ratio and caspase 3 cleavage assay. This study elucidated the neurotoxicity of AZOX and explained the possible cure from it.

Dual Buffering Inverse Design of Three-Dimensional Graphene-Supported Sn-TiO2 Anodes for Durable Lithium-Ion Batteries.

Stable battery operation involving high-capacity electrode materials such as tin (Sn) has been plagued by dimensional instability-driven battery degradation despite the potentially accessible high energy density of batteries. Rational design of Sn-based electrodes inevitably requires buffering or passivation layers mostly in a multi-stacked manner with sufficient void inside the shells. However, undesirable void engineering incurs energy loss and shell fracture during the strong calendaring process. Here, this study reports an inverse design of freestanding 3D graphene electrodes sequentially passivated by capacity-contributing Sn and protective/buffering TiO2 . Monodisperse polymer bead templates coated with inner TiO2 and outer SnO2 layers generate regular macropores and 3D interconnected graphene framework while the inner TiO2 shell turns inside out to fully passivate the surface of Sn nanoparticles during the thermal annealing process. The prepared 3D freestanding electrodes are simultaneously buffered by electronically conductive and flexible graphene support and ion-permeable/mechanically stable TiO2 nanoshells, thus greatly extending the cycle life of batteries more than 5000 cycles at 5 C with a reversible capacity of ≈520 mAh g-1 with a high volumetric energy density.

Long-term clinical course and outcomes of immunoglobulin G4-related lung disease.

BACKGROUND: Immunoglobulin G4-related lung disease (IgG4-RLD) is the pulmonary manifestation of a systemic fibroinflammatory disease characterized by lymphoplasmacytic infiltration with an abundance of IgG4-positive plasma cells. Long-term clinical course and outcomes of IgG4-RLD remain unclear. We aimed to identify clinical characteristics, treatment outcomes, and longitudinal pulmonary function changes in patients with IgG4-RLD according to the radiologic classification. METHODS: Chest computed tomography findings of 37 subjects were classified into five subtypes: solid nodular, bronchovascular, alveolar interstitial, round ground glass opacity, and alveolar consolidative. Radiologic treatment outcomes and longitudinal pulmonary function changes were compared among the different radiologic subtypes. RESULTS: The mean age of the subjects was 55.6 years, and 78.4% were male. Among the five radiologic subtypes, alveolar consolidative and solid nodular type were most common, accounting for approximately 29.7% each of the total cases. Prednisone with or without azathioprine was administered to 31 patients (median treatment duration 14 months). In the treated patients, serial images showed complete response or partial response in 77.4%. However, relapse was documented in 25.0% of those who showed complete or partial response. In patients whose longitudinal lung function data were available (n = 20), the lung function was found to be stable during follow-up. Alveolar consolidative type showed the highest complete response rate, whereas alveolar interstitial type showed the lowest response rate, either complete or partial. CONCLUSIONS: Most patients showed a favorable outcome with regards to radiologic improvement and maintenance of pulmonary function; however, the response differed according to the radiologic subtype.

Effect of adjunctive corticosteroid on 28-day mortality in neutropenic patients with septic shock.

The role of adjunctive corticosteroid in septic shock remains debatable, and its role has not been assessed in neutropenic patients. We evaluated whether hydrocortisone reduces 28-day mortality in neutropenic patients with septic shock. We conducted a retrospective cohort study between January 2012 and May 2017 at a tertiary care center in South Korea. Patients who developed septic shock treated with at least one vasopressor and whose absolute neutrophil count was < 1000 cells/µL were included. Patients were classified into a steroid and a no-steroid group. The primary outcome of the study was 28-day mortality. Propensity score matching was used to adjust baseline characteristics and disease severity between the groups. Of the 287 patients analyzed, 189 were classified in the no-steroid group and 98 in the steroid group. Fifty propensity score-matched pairs were compared for the study outcomes. We found no significant difference in 28-day mortality between patients treated with and without steroid after propensity score matching (38.0% and 42.0%, respectively; p = 0.838). Incidences of pneumonia and gastrointestinal bleeding were more frequent in the steroid group, but it was not statistically significant after matching. In conclusion, adjunctive hydrocortisone was not associated with reduced 28-day mortality in neutropenic patients with septic shock.

Clinical outcomes and risk factors of thromboprophylaxis with rivaroxaban versus aspirin in patients undergoing hip arthroplasty in low-incidence population: A nationwide study in Korea.

PURPOSE: We aimed to evaluate the efficacy and safety of rivaroxaban in thromboprophylaxis compared with those of aspirin in real-world patients who underwent hip arthroplasty using nationwide claims data. METHODS: Patients aged more than or equal to 18 years with at least one hip arthroplasty including total and partial hip replacements and hip replacement revisions during July 2009 to June 2013 were identified from the Health Insurance Review and Assessment (HIRA) database. The study outcome was incidence rate of thromboembolic events and anticoagulation-related major bleeding within 90 days of hip arthroplasty. RESULTS: The incidence of overall venous thromboembolism (VTE) within 90-day postsurgery was significantly higher in the aspirin cohort than it was in the rivaroxaban cohorts. Bleeding events associated with pharmacological thromboprophylaxis in patients who received rivaroxaban were not significantly different from that in aspirin-treated patients. In aspirin cohorts, 65.7% of patients received less than 3-week treatment while about half received a less than 14-day treatment, and 31.7% received more than 3-week treatment in the rivaroxaban cohort. CONCLUSIONS: This study demonstrates that rivaroxaban was more effective in preventing VTE following hip arthroplasty without raising bleeding risks in clinical settings. Age more than or equal to 80 years, women, and a history of thromboembolism were the risk factors of VTE incidence.

Bronchial Thermoplasty in Patients with Severe Uncontrolled Asthma: First Korean Cases.

Bronchial thermoplasty is a nonpharmacological treatment for severe asthma that delivers thermal energy to the bronchial walls and reduces hypertrophied smooth muscle mass. Previous studies have shown its efficacy and safety, resulting in approval from the Food and Drug Administration in 2010. In Korea, the first bronchial thermoplasty was carried out in 2014; 4 patients have undergone the procedure so far. This case series presents the medical history and treatment outcomes of these 4 patients. All patients presented with uncontrolled asthma despite optimal medical treatment. Bronchial thermoplasty was performed at the right lower lobe, left lower lobe, and both upper lobes in order at 3-week intervals. All procedures were performed under general anesthesia. Two patients had significant decreases in exacerbations and required a lower dose of inhaled corticosteroids after the procedure. One patient had slightly fewer exacerbations but failed to reduce the use of systemic corticosteroids. One patient had no change in symptoms. One limitation of bronchial thermoplasty is the difficulty of predicting clinical responders. However, since more therapeutic options are needed in the management of severe asthma, especially T2-low asthma, discussion with experts about the feasibility and necessity of bronchial thermoplasty will ensure the best possible care.

MicroRNA-137 Inhibits Cancer Progression by Targeting Del-1 in Triple-Negative Breast Cancer Cells.

MicroRNAs (miRNAs) can be used to target a variety of human malignancy by targeting their oncogenes or tumor suppressor genes. The developmental endothelial locus-1 (Del-1) might be under miRNA regulation. This study investigated microRNA-137 (miR-137) function and Del-1 expression in triple-negative breast cancer (TNBC) cells and tissues. Del-1 mRNA and miRNA-137 levels were determined via qRT-PCR in breast cancer cells (MDA-MB-231, MCF7, SK-BR3, and T-47D) and tissues from 30 patients with TNBC. The effects of miR-137 on cell proliferation, migration, and invasion were determined using MTT assays, wound healing, and Matrigel transwell assays. The luciferase reporter assay revealed direct binding of miR-137 to the 3'-UTR of Del-1. miR-137 inhibited cell proliferation, migration, and invasion of MDA-MB-231 cells. Among the 30 TNBC specimens, miR-137 was downregulated and Del-1 level in plasma was significantly elevated relative to normal controls. It is concluded that miR-137 regulates Del-1 expression in TNBC by directly binding to the Del-1 gene and cancer progression. The results implicate miR-137 as a new therapeutic biomarker for patients with TNBC.