Tumor shape as a prognostic factor for the growth of intracanalicular vestibular schwannoma: a long-term observational study.

PURPOSE: To evaluate the predictive factors of tumor growth in patients with vestibular schwannoma (VS) managed with the wait-and-scan approach. METHODS: The data of 31 patients diagnosed with intracanalicular VS and followed for > 5 years were retrospectively analyzed. VS was diagnosed according to MRI findings and tumor growth was monitored. Tumor growth was defined as an increase of 2 mm or more in the maximal tumor diameter. The association between the initial tumor size and shape and tumor growth was assessed. RESULTS: Tumor growth was observed in 16 of 31 patients (51.6%) over a mean follow-up duration of 7.3 years. The initial tumor size was not statistically correlated with tumor growth. However, fusiform or cylindrical tumors exhibited higher growth rates than oval or round tumors. Additionally, a significant correlation was observed between cerebellopontine angle extension and tumor shape. CONCLUSION: In this study, 51.6% of the patients with intracanalicular VS who were managed with the wait-and-scan strategy over a follow-up period of > 5 years showed tumor growth. Tumor shape, especially fusiform or cylindrical shape, was found to be a significant predictor of tumor growth.

Streptomyces guryensis sp. nov. exhibiting antimicrobial activity, isolated from riverside soil.

A novel Gram-stain-positive, aerobic actinobacterial strain designated NR30T was isolated from riverside soil. A polyphasic approach was employed for the taxonomic characterization of NR30T. The strain developed extensively branched light brown to light pink substrate mycelia and light grey aerial mycelia, and produced spiny spores in loose spiral spore chains on ISP 3 and 4 agars. NR30T grew at 10-40°C (optimum, 30°C), at pH 6.0-9.0 (optimum, pH 8.0) and in the presence of 0-3 % NaCl (optimum, 0 %). Analysis of 16S rRNA gene sequences indicated that NR30T represents a member of the genus Streptomyces. NR30T shared the highest 16S rRNA gene sequence similarity with Streptomyces cyaneus NRRL B-2296T (98.6 %). On the basis of orthologous average nucleotide identity, NR30T was most closely related to Streptomyces panaciradicis NBRC 109811T with 86.3 % identity. The results of the digital DNA-DNA hybridization analysis also indicated low levels of relatedness with other species, as the highest value was observed with Streptomyces panaciradicis NBRC 109811T (31.1 %). The major fatty acids of the strain were anteiso-C15 : 0, C16 : 0, iso-C16 : 0 and anteiso-C17 : 0. The major respiratory quinones were MK-9(H8) and MK-9(H6). The diagnostic polar lipids were diphosphatidylglycerol, phosphatidylethanolamine and phosphatidylinositol mannoside. The major cell wall diamino acid was ll-diaminopimelic acid, and the characteristic whole-cell sugars were rhamnose, ribose and glucose. The DNA G+C content was 70.3 mol %. NR30T exhibited antimicrobial activity against several Gram-negative bacteria and yeasts. On the basis of the results of both phenotypic and phylogenetic analyses, strain NR30T evidently represents a novel species of the genus Streptomyces, and the name Streptomyces guryensis sp. nov. (type strain=NR30T =KCTC 49653T=LMG 32476T) is proposed accordingly.

Brevibacillus humidisoli sp. nov., a moderately thermoalkaliphilic and halotolerant species isolated from riverside soil.

A Gram-stain-positive, aerobic, rod-shaped, motile, and endospore-forming bacterial strain designated MMS20-4M-10-YT was isolated from riverside soil and subjected to taxonomic characterization. Strain MMS20-4M-10-YT was moderately thermophilic, alkaliphilic and halotolerant, as the strain grew at 25-50 °C (optimum, 45 °C), at pH 7.0-10.0 (optimum, pH 8.0) and in the presence of 0-6 % NaCl (optimum, 0 %). Analysis of 16S rRNA gene sequences indicated that MMS20-4M-10-YT fell into a phylogenetic cluster belonging to the genus Brevibacillus. Strain MMS20-4M-10-YT showed the highest 16S rRNA gene sequence similarity to Brevibacillus marinus SCSIO 07484T (96.7 %). Based on the reults of orthologous average nucleotide identity analysis, MMS20-4M-10-YT was again mostly related to B. marinus SCSIO 07484T with 78.0 % identity, which also shared the highest average nucleotide identity of 68.0 %. In contrast, the digital DNA-DNA relatedness analysis indicated that Aneureibacillus migulanus DSM 2895T was the closest species with 29.5 % similarity. The genome-based analyses indicated that all compared species showed low genomic relatedness with MMS20-4M-10-YT. The major fatty acids of the strain were anteiso-C15 : 0, iso-C15 : 0, iso-C16 : 0 and iso-C17 : 0, the major respiratory quinone was MK-7, the diagnostic polar lipids were phosphatidyl-N-methylethanolamine, diphosphatidylglycerol, phosphatidylethanolamine and phosphatidylglycerol, and diagnostic cell-wall diamino acid was meso-diaminopimelic acid, which was consistent with the general chemotaxonomic features of the genus. The total length of the genome was 4.91 Mbp and the DNA G+C content was 51.8 mol%. Based on both phenotypic and phylogenetic evidence, strain MMS20-4M-10-YT should be classified as representing a novel species of the genus Brevibacillus, for which a name Brevibacillus humidisoli sp. nov. (type strain=MMS20-4M-10-YT=KCTC 43333T=LMG 32359T) is proposed.

Discovery of New Anti-Cancer Agents against Patient-Derived Sorafenib-Resistant Papillary Thyroid Cancer.

Thyroid cancer is the most well-known type of endocrine cancer that is easily treatable and can be completely cured in most cases. Nonetheless, anti-cancer drug-resistant metastasis or recurrence may occur and lead to the failure of cancer therapy, which eventually leads to the death of a patient with cancer. This study aimed to detect novel thyroid cancer target candidates based on validating and identifying one of many anti-cancer drug-resistant targets in patient-derived sorafenib-resistant papillary thyroid cancer (PTC). We focused on targeting the sarco/endoplasmic reticulum calcium ATPase (SERCA) in patient-derived sorafenib-resistant PTC cells compared with patient-derived sorafenib-sensitive PTC cells. We discovered novel SERCA inhibitors (candidates 33 and 36) by virtual screening. These candidates are novel SERCA inhibitors that lead to remarkable tumor shrinkage in a xenograft tumor model of sorafenib-resistant patient-derived PTC cells. These results are clinically valuable for the progression of novel combinatorial strategies that facultatively and efficiently target extremely malignant cancer cells, such as anti-cancer drug-resistant PTC cells.

Blood Krebs von den Lungen-6 levels predict treatment response to antifibrotic therapy in patients with idiopathic pulmonary fibrosis.

BACKGROUND: Antifibrotic therapy can slow disease progression (DP) in patients with idiopathic pulmonary fibrosis (IPF). However, the prognostic biomarkers for DP in patients with IPF receiving antifibrotic therapy have not been identified. Therefore, we aimed to evaluate the prognostic efficacy of serum Krebs von den Lungen-6 (KL-6) for DP in patients with IPF receiving antifibrotic therapy. METHODS: The clinical data of 188 patients with IPF who initiated antifibrotic therapy at three tertiary hospitals was retrospectively analyzed. DP was defined as a relative decline in forced vital capacity (FVC) ≥ 10%, diffusing capacity for carbon monoxide ≥ 15%, acute exacerbation, or deaths during 6 months after antifibrotic therapy. RESULTS: The mean age of patients was 68.9 years, 77.7% were male, and DP occurred in 43 patients (22.9%) during follow-up (median, 7.6 months; interquartile range, 6.2-9.8 months). There was no difference in baseline KL-6 levels between the DP and no-DP groups; however, among patients with high baseline KL-6 levels (≥ 500 U/mL), changes in KL-6 levels over 1 month were higher in the DP group than those in the non-DP group, and higher relative changes in KL-6 over 1 month were independently associated with DP (odds ratio, 1.043; 95% confidence interval 1.005-1.084) in the multivariable logistic analysis adjusted for age and FVC. In the receiver operating characteristic curve analysis, the 1-month change in KL-6 was also useful for predicting DP (area under the curve = 0.707; P < 0.012). CONCLUSIONS: Our data suggest that the relative change in KL-6 over 1 month might be useful for predicting DP in patients with IPF receiving antifibrotic therapy when baseline KL6 is high.

Streptomyces montanisoli sp. nov., exhibiting antimicrobial activity, isolated from mountain soil around a decaying tree.

A Gram-stain-positive, aerobic actinobacterial strain designated MMS17-BM035T isolated from mountain soil around a decaying tree was subjected to taxonomic characterization. The isolate developed extensively branched substrate mycelia and white aerial hyphae on International Streptomyces Project 2 agar. Strain MMS17-BM035T grew at 15-34 °C (optimum, 30 °C), at pH 5.0-8.0 (optimum, pH 7.0) and in the presence of 0-6 % NaCl (optimum, 0 %). Analysis of 16S rRNA gene sequences indicated that MMS17-BM035T fell into a phylogenetic cluster belonging to the genus Streptomyces. MMS17-BM035T shared the highest sequence similarity of 99.45 % with Streptomyces fuscigenes JBL-20T, and no higher than 98.7 % with other species of Streptomyces. Based on the orthologous average nucleotide identity, MMS17-BM035T was again mostly related to S. fuscigenes JBL-20T with 84.14 % identity, and less than 80 % with other species. The digital DNA-DNA hybridization analysis also indicated low levels of relatedness with related species, as the highest value was observed with S. fuscigenes JBL-20T (28.8 %). The major fatty acids of the strain were anteiso-C15 : 0, a summed feature (consisting of C18 : 1 ω7c/C18 : 1 ω6c), iso-C15 : 0, C16 : 0 and C20 : 0. The major respiratory quinones were MK-9(H4) and MK-9(H6). The diagnostic polar lipids were diphosphatidylglycerol, phosphatidylethanolamine and phosphatidylinositolmannoside. The major cell-wall diamino acid was ll-diaminopimelic acid, and the characteristic whole-cell sugars were glucose and ribose. The DNA G+C content was 72.1 mol%. Strain MMS17-BM035T exhibited antimicrobial activity against several Gram-positive bacteria and yeasts. Based on both phenotypic and phylogenetic evidences, strain MMS17-BM035T should be classified as representing a novel species, for which the name Streptomyces montanisoli sp. nov. (type strain=MMS17-BM035T=KCTC 49544T=JCM 34528T) is proposed.

Drug Discovery Using Evolutionary Similarities in Chemical Binding to Inhibit Patient-Derived Hepatocellular Carcinoma.

Drug resistance causes therapeutic failure in refractory cancer. Cancer drug resistance stems from various factors, such as patient heterogeneity and genetic alterations in somatic cancer cells, including those from identical tissues. Generally, resistance is intrinsic for cancers; however, cancer resistance becomes common owing to an increased drug treatment. Unfortunately, overcoming this issue is not yet possible. The present study aimed to evaluate a clinical approach using candidate compounds 19 and 23, which are sarcoplasmic/endoplasmic reticulum calcium ATPase (SERCA) inhibitors, discovered using the evolutionary chemical binding similarity method. mRNA sequencing indicated SERCA as the dominant marker of patient-derived anti-cancer drug-resistant hepatocellular carcinoma (HCC), but not of patient-derived anti-cancer drug-sensitive HCC. Candidate compounds 19 and 23 led to significant tumor shrinkage in a tumor xenograft model of anti-cancer drug-resistant patient-derived HCC cells. Our results might be clinically significant for the development of novel combinatorial strategies that selectively and efficiently target highly malignant cells such as drug-resistant and cancer stem-like cells.

Potential Therapeutic Agents against Paclitaxel-And Sorafenib-Resistant Papillary Thyroid Carcinoma.

Thyroid carcinoma, a disease in which malignant cells form in the thyroid tissue, is the most common endocrine carcinoma, with papillary thyroid carcinoma (PTC) accounting for nearly 80% of total thyroid carcinoma cases. However, the management of metastatic or recurrent therapy-refractory PTC is challenging and requires complex carcinoma therapy. In this study, we proposed a new clinical approach for the treatment of therapy-refractory PTC. We identified sarco/endoplasmic reticulum calcium ATPase (SERCA) as an essential factor for the survival of PTC cells refractory to the treatment with paclitaxel or sorafenib. We validated its use as a potential target for developing drugs against resistant PTC, by using patient-derived paclitaxel- or sorafenib-resistant PTC cells. We further discovered novel SERCA inhibitors, candidates 7 and 13, using the evolutionary chemical binding similarity method. These novel SERCA inhibitors determined a substantial reduction of tumors in a patient-derived xenograft tumor model developed using paclitaxel- or sorafenib-resistant PTC cells. These results could provide a basis for clinically meaningful progress in the treatment of refractory PTC by identifying a novel therapeutic strategy: using a combination therapy between sorafenib or paclitaxel and specific SERCA inhibitors for effectively and selectively targeting extremely malignant cells such as antineoplastic-resistant and carcinoma stem-like cells.

Maternal and paternal effects on hyperuricaemia: a cross-sectional study from the seventh Korean National Health and Nutrition Examination Survey.

OBJECTIVE: As the heritability of hyperuricaemia remains largely unexplained, we analysed the association between parental and offspring hyperuricaemia at the phenotype level. METHODS: This cross-sectional study included data on 2373 offspring and both-parent pairs from the seventh Korean National Health and Nutrition Examination Survey. Logistic regression and generalised estimating equation analysis were used to evaluate the association between offspring and parental hyperuricaemia adjusting for metabolic risk factors and alcohol intake. RESULTS: Both maternal and paternal hyperuricaemia were associated with offspring hyperuricaemia among teenagers, but from the age of 20 years, a strong association was observed between offspring and paternal, rather than, maternal hyperuricaemia, and this could not be explained by metabolic risk factors such as obesity. However, there was a positive interaction between offspring alcohol intake and parental hyperuricaemia, and there was a stronger association between terciles of offspring alcohol intake and hyperuricaemia in the presence of parental hyperuricaemia: T1 (reference), T2 odds ratio (OR) 1.1 (0.3-4.6), and T3 OR 3.3 (1.4-7.9) (P for trend .017) vs. T1 (reference), T2 OR 0.7 (0.3-1.9), and T3 OR 1.1 (0.6-2.2) (P for trend .974). CONCLUSION: These results suggest a gene-environment interaction, especially with respect to alcohol intake for hyperuricaemia in Korean adults.

Clinically amyopathic dermatomyositis presenting with isolated facial edema complicated by acute respiratory failure: a case report.

BACKGROUND: In clinically amyopathic dermatomyositis, the hallmark cutaneous manifestations are the key to diagnosis. We report a case of clinically amyopathic dermatomyositis which presented with facial edema as the sole cutaneous manifestation and was later complicated by acute respiratory failure leading to death. CASE PRESENTATION: A 58-year-old woman presented with edema of the face that had developed approximately one year ago. There was no weakness in the extremities, and the serum creatine kinase level was within normal range. On MRI, there was diffuse edematous change in the bilateral masticator and extra-ocular muscles, accompanied by subcutaneous fat infiltration in the face. A shared decision was made to defer muscle biopsy in the facial muscles. The facial swelling almost resolved with medium-dose glucocorticoid therapy but relapsed in days at glucocorticoid doses lower than 15 mg/day. Combination therapy with either azathioprine, mycophenolate, or methotrexate was not successful in maintaining clinical remission, and the swelling became more severe after relapses. A US-guided core-needle biopsy was subsequently performed in the right masseter muscle. On pathologic examination, there was a patchy CD4 + T cell-dominant lymphoplasmacytic infiltration in the stroma, necrosis of the myofibrils and prominent perifascicular atrophy. Based on those findings, a diagnosis of clinically amyopathic dermatomyositis was made. Therapy with gamma-globulin was not effective in maintaining remission. In the sixth week after starting rituximab, she presented to emergency room with altered mental state from acute respiratory failure. Despite treatment with antibiotics, glucocorticoid pulse, cyclosporin, and polymyxin B-immobilized fiber column direct hemoperfusion, she died three weeks later from persistent hypoxemic respiratory failure. CONCLUSIONS: This case showed the full spectrum and severity of internal organ involvement of dermatomyositis, although the patient presented exclusively with subcutaneous edema limited to the head. The prognosis may be more closely associated with a specific auto-antibody profile than the benign-looking initial clinical manifestation. Close follow-up of lung involvement with prophylactic treatment for Pneumocystis pneumonia and prompt implementation of emerging therapeutic regimens may improve the outcome.

Pleuroparenchymal fibroelastosis in patients with idiopathic pulmonary fibrosis.

BACKGROUND AND OBJECTIVE: PPFE is characterized by fibrosis in the pleura and subpleural lung parenchyma in the upper lobes, while other types of ILD, mainly UIP, can be observed in about half of the patients in their lower lobes. The aim of this study was to evaluate the clinical significance of the radiologically defined PPFE in patients with IPF. METHODS: Clinical data and chest CT images were retrospectively analysed in 445 patients with IPF (biopsy-proven cases, n = 165). The radiological criteria of PPFE were defined as follows: (i) bilateral subpleural dense fibrosis with or without pleural thickening in the upper lobes, (ii) evidence of disease progression and (iii) no clinical evidence of identifiable aetiologies. RESULTS: The median follow-up period was 43.0 months. The mean age of the patients was 66.4 years and 76.4% were male. PPFE was identified in 28 patients (6.3%). The PPFE group showed lower BMI and lung function (FVC and TLC) at baseline, more frequent pneumothorax and pneumomediastinum, higher decline rates in lung function and poorer prognosis during follow-up than the no-PPFE group. PPFE was an independent risk factor (HR = 2.953, 95% CI: 1.350-6.460, P = 0.007) for pneumothorax or pneumomediastinum, but not for mortality in patients with IPF. CONCLUSION: Among patients with IPF, the PPFE group, when compared to the no-PPFE group, showed lower BMI and lung function and showed more frequent complications and poorer survival during follow-up.

Genetic Dissection of Alzheimer's Disease Using Drosophila Models.

Alzheimer's disease (AD), a main cause of dementia, is the most common neurodegenerative disease that is related to abnormal accumulation of the amyloid ß (Aß) protein. Despite decades of intensive research, the mechanisms underlying AD remain elusive, and the only available treatment remains symptomatic. Molecular understanding of the pathogenesis and progression of AD is necessary to develop disease-modifying treatment. Drosophila, as the most advanced genetic model, has been used to explore the molecular mechanisms of AD in the last few decades. Here, we introduce Drosophila AD models based on human Aß and summarize the results of their genetic dissection. We also discuss the utility of functional genomics using the Drosophila system in the search for AD-associated molecular mechanisms in the post-genomic era.

Fibulin-3 negatively regulates ALDH1 via c-MET suppression and increases γ-radiation-induced sensitivity in some pancreatic cancer cell lines.

Fibulin-3 (FBLN-3) has been postulated to be either a tumor suppressor or promoter depending on the cell type, and hypermethylation of the FBLN-3 promoter is often associated with human disease, especially cancer. We report that the promoter region of the FBLN-3 was significantly methylated (>95%) in some pancreatic cancer cell lines and thus FBLN-3 was poorly expressed in pancreatic cancer cell lines such as AsPC-1 and MiaPaCa-2. FBLN-3 overexpression significantly down-regulated the cellular level of c-MET and inhibited hepatocyte growth factor-induced c-MET activation, which were closely associated with γ-radiation resistance of cancer cells. Moreover, we also showed that c-MET suppression or inactivation decreased the cellular level of ALDH1 isozymes (ALDH1A1 or ALDH1A3), which serve as cancer stem cell markers, and subsequently induced inhibition of cell growth in pancreatic cancer cells. Therefore, forced overexpression of FBLN-3 sensitized cells to cytotoxic agents such as γ-radiation and strongly inhibited the stemness and epithelial to mesenchymal transition (EMT) property of pancreatic cancer cells. On the other hand, if FBLN3 was suppressed in FBLN-3-expressing BxPC3 cells, the results were opposite. This study provides the first demonstration that the FBLN-3/c-MET/ALDH1 axis in pancreatic cancer cells partially modulates stemness and EMT as well as sensitization of cells to the detrimental effects of γ-radiation.

Disturbance of DKK1 level is partly involved in survival of lung cancer cells via regulation of ROMO1 and γ-radiation sensitivity.

Dickkopf1 (DKK1), a secreted protein involved in embryonic development, is a potent inhibitor of the Wnt signaling pathway and has been postulated to be a tumor suppressor or tumor promoter depending on the tumor type. In this study, we showed that DKK1 was expressed differently among non-small-cell lung cancer cell lines. The DKK1 expression level was much higher in A549 cells than in H460 cells. We revealed that blockage of DKK1 expression by silencing RNA in A549 cells caused up-regulation of intracellular reactive oxygen species (ROS) modulator (ROMO1) protein, followed by partial cell death, cell growth inhibition, and loss of epithelial-mesenchymal transition property caused by ROS, and it also increased γ-radiation sensitivity. DKK1 overexpression in H460 significantly inhibited cell survival with the decrease of ROMO1 level, which induced the decrease of cellular ROS. Thereafter, exogenous N-acetylcysteine, an antioxidant, or hydrogen peroxide, a pro-oxidant, partially rescued cells from death and growth inhibition. In each cell line, both overexpression and blockage of DKK1 not only elevated p-RB activation, which led to cell growth arrest, but also inactivated AKT/NF-kB, which increased radiation sensitivity and inhibited cell growth. This study is the first to demonstrate that strict modulation of DKK1 expression in different cell types partially maintains cell survival via tight regulation of the ROS-producing ROMO1 and radiation resistance.

Diagnostic Approaches for Idiopathic Pulmonary Fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, fibrosing interstitial pneumonia with a very poor prognosis. Accurate diagnosis of IPF is essential for good outcomes but remains a major medical challenge due to variability in clinical presentation and the shortcomings of existing diagnostic tests. Medical history collection is the first and most important step in the IPF diagnosis process; the clinical probability of IPF is high if the suspected patient is 60 years or older, male, and has a history of cigarette smoking. Systemic assessment for connective tissue disease is essential in the initial evaluation of patients with suspected IPF to identify potential causes of interstitial lung disease (ILD). Radiologic examination using high-resolution computed tomography plays a pivotal role in the evaluation of patients with ILD, and prone and expiratory computed tomography images can be considered. If additional tests such as surgical lung biopsy or transbronchial lung cryobiopsy are needed, transbronchial lung cryobiopsy should be considered as an alternative to surgical lung biopsy in medical centers with experience performing this procedure. Diagnosis through multidisciplinary discussion (MDD) is strongly recommended as MDD has become the cornerstone for diagnosis of IPF, and the scope of MDD has expanded to monitoring of disease progression and suggestion of appropriate treatment options.

Efficacy of Botulinum Toxin Injection for Airway Management in Patients with Transient Bilateral Vocal Fold Paresis Following Thyroidectomy: A Prospective Study.

OBJECTIVES: This prospective study evaluated the effectiveness and safety of botulinum toxin injection for airway management in patients with transient bilateral vocal fold paresis (BVFP) after thyroidectomy. STUDY DESIGN: Prospective clinical study. METHODS: A prospective study was conducted at Soonchunhyang University, Bucheon, Korea, between March 2005 and February 2023. This study enrolled 12 patients with BVFP after thyroidectomy who received botulinum toxin injections into the thyroarytenoid muscles. Vocal fold mobility and airway distress were assessed using a flexible laryngoscope before and after injection. RESULTS: Of the 3018 thyroidectomy patients, 12 (0.39%) developed transient BVFP after surgery. Under the guidance of laryngeal electromyography, 3.6 ± 0.6 IU botulinum toxin was administered into the bilateral thyroarytenoid muscles. Notably, nine patients (75%) received a single injection, whereas three (25%) received an additional injection after 7days. The mean time for vocal fold movement recovery was 33.2 ± 17.2days after injection; conventional destructive procedures for BVFP were avoided in 10 of the 12 patients (83.3%). CONCLUSIONS: Botulinum toxin injection offers a novel approach to airway management in patients with transient BVFP after thyroidectomy. LEVEL OF EVIDENCE: Level 4.

Efficacy of Digital Therapeutics for Pulmonary Rehabilitation: A Multi-Center, Randomized Controlled Trial.

BACKGROUND: This study aimed to investigate the efficacy and safety of digital therapeutics (DTx), EASYBREATH, for pulmonary rehabilitation (PR) in patients with chronic respiratory diseases (CRDs). MATERIALS AND METHODS: This prospective randomized controlled trial was conducted at multiple centers. Participants were randomly allocated 1:1 to the DTx group (DTxG), provided with DTx using EASYBREATH. The DTxG underwent an 8-week PR program with evaluations conducted at baseline, four weeks, and eight weeks. The control group (CG) underwent one PR session and was advised to exercise and undergo the same evaluation. The primary outcome was the change in six-minute walking distance (6MWD) over eight weeks, and secondary outcomes included changes in scores of Modified Medical Research Council (mMRC), chronic obstructive pulmonary disease assessment test (CAT), and St. George's respiratory questionnaire (SGRQ). RESULTS: The change in 6MWD after eight weeks demonstrated a significant difference between the DTxG and CG (57.68 m vs. 21.71 m, p = 0.0008). The change in mMRC scores (p = 0.0008), CAT scores (p < 0.0001), and total SGRQ scores (p = 0.0003) also showed a significant difference between the groups after eight weeks. CONCLUSIONS: EASYBREATH significantly improved exercise capacity, alleviated dyspnea, and enhanced the overall quality of life at eight weeks. EASYBREATH is a highly accessible, time-efficient, and effective treatment option for CRD with high compliance.

A study on the prevalence and prognosis of progressive pulmonary fibrosis: A retrospective observational study.

Interstitial lung disease (ILD) encompasses a heterogeneous group of more than 200 diffuse parenchymal lung diseases with various clinical courses. Disease progression is one of the most important prognostic factors, and, the definition of progressive pulmonary fibrosis (PPF) has recently been established. This study aimed to estimate the prevalence, risk factors, and prognosis of PPF among patients with non-idiopathic pulmonary fibrosis (IPF) in real-world practice. A total of 215 patients were retrospectively analyzed between January 2010 and June 2023 at the Haeundae Paik Hospital in the Republic of Korea. According to the criteria proposed in 2022 by Raghu et al, PPF defined as a condition that satisfies 2 or more of the following in the past year: worsening of respiratory symptoms, physiological evidence of disease progression, and radiological evidence of disease progression. The median age of the subjects was 67 years and 63.7% were female. A total of 40% was diagnosed with PPF and connective tissue disease-associated ILD (52.3%) was the most common type, followed by nonspecific interstitial pneumonitis (NSIP) (25.6%) and cryptogenic organizing pneumonitis (16.3%). In multivariate logistic regression for predicting PPF, both the use of steroids and immunosuppressants (OR: 2.57, 95% CI: 1.41-4.67, P = .002) and home oxygen use (OR: 25.17, 95% CI: 3.21-197.24, P = .002) were independent risk factors. During the follow-up period, the mortality rate was significantly higher in the PPF group than in the non-PPF group (24.4% vs 2.3%, P < .001). In the survival analysis using the Cox proportional hazard regression model, disease progression, older age and lower forced vital capacity (FVC) were independent risk factors for mortality. Our study demonstrated that the prevalence of PPF was 40%. Concomitant therapy of steroids with an immunosuppressants and home oxygen use are risk factors for PPF. PPF itself was significantly associated with high mortality rates. Risk factors for mortality were disease progression, older age, and lower FVC.

Beyond One-Size-Fits-All: Tailoring Teicoplanin Regimens for Normal Renal Function Patients Using Population Pharmacokinetics and Monte Carlo Simulation.

In patients with normal renal function, significant teicoplanin dose adjustments are often necessary. This study aimed to develop a population pharmacokinetic (PK) model for teicoplanin in healthy adults and use it to recommend optimal dosage regimens for patients with normal renal function. PK samples were obtained from 12 subjects and analyzed using a population approach. The derived parameters informed Monte Carlo simulations for dosing recommendations. The PK profile was best described using a three-compartment model, in which the estimated glomerular filtration rate calculated via the CKD-EPI equation and adjusted for body surface area was identified as a significant covariate affecting total clearance. For pathogens with a minimum inhibitory concentration of 1 mg/L, a loading dose (LD) of 14 mg/kg administered every 12 h for four doses, followed by a maintenance dose (MD) of 16 mg/kg administered every 24 h, is recommended. These findings indicate the need for dosage adjustments, such as increasing the LD and MD or decreasing the dosing interval of MD in patients with normal renal function. Because of the long half-life of teicoplanin and the requirement for long-term administration, therapeutic drug monitoring at strategic intervals is important to avoid nephrotoxicity associated with elevated trough concentrations.