Background: Nonalcoholic steatohepatitis (NASH) is a liver disease caused by obesity that leads to hepatic lipoapoptosis, resulting in fibrosis and cirrhosis. However, the mechanism underlying NASH is largely unknown, and there is currently no effective therapeutic agent against it. DWN12088, an agent used for treating idiopathic pulmonary fibrosis, is a selective prolyl-tRNA synthetase (PRS) inhibitor that suppresses the synthesis of collagen. However, the mechanism underlying the hepatoprotective effect of DWN12088 is not clear. Therefore, we investigated the role of DWN12088 in NASH progression. Methods: Mice were fed a chow diet or methionine-choline deficient (MCD)-diet, which was administered with DWN12088 or saline by oral gavage for 6 weeks. The effects of DWN12088 on NASH were evaluated by pathophysiological examinations, such as real-time quantitative reverse transcription polymerase chain reaction, immunoblotting, biochemical analysis, and immunohistochemistry. Molecular and cellular mechanisms of hepatic injury were assessed by in vitro cell culture. Results: DWN12088 attenuated palmitic acid (PA)-induced lipid accumulation and lipoapoptosis by downregulating the Rho-kinase (ROCK)/AMP-activated protein kinase (AMPK)/sterol regulatory element-binding protein-1c (SREBP-1c) and protein kinase R-like endoplasmic reticulum kinase (PERK)/α subunit of eukaryotic initiation factor 2 (eIF2α)/activating transcription factor 4 (ATF4)/C/EBP-homologous protein (CHOP) signaling cascades. PA increased but DWN12088 inhibited the phosphorylation of nuclear factor-κB (NF-κB) p65 (Ser536, Ser276) and the expression of proinflammatory genes. Moreover, the DWN12088 inhibited transforming growth factor β (TGFβ)-induced pro-fibrotic gene expression by suppressing TGFβ receptor 1 (TGFβR1)/Smad2/3 and TGFβR1/glutamyl-prolyl-tRNA synthetase (EPRS)/signal transducer and activator of transcription 6 (STAT6) axis signaling. In the case of MCD-diet-induced NASH, DWN12088 reduced hepatic steatosis, inflammation, and lipoapoptosis and prevented the progression of fibrosis. Conclusion Our findings provide new insights about DWN12088, namely that it plays an important role in the overall improvement of NASH. Hence, DWN12088 shows great potential to be developed as a new integrated therapeutic agent for NASH.

OBJECTIVES: Inconsistent results are available regarding the association between low estimated glomerular filtration rate (eGFR) and lung cancer risk. We aimed to explore the risk of lung cancer according to eGFR category in the Korean population. METHODS: We included 358,293 adults who underwent health checkups between 2009 and 2010, utilizing data from the National Health Insurance Service-National Sample Cohort. Participants were categorized into 3 groups based on their baseline eGFR, as determined using the Chronic Kidney Disease Epidemiology Collaboration equation: group 1 (eGFR ≥90 mL/min/1.73 m2), group 2 (eGFR ≥60 to <90 mL/min/1.73 m2), and group 3 (eGFR <60 mL/min/1.73 m2). Incidences of lung cancer were identified using the corresponding codes from the International Classification of Diseases, 10th revision. Multivariate Cox proportional hazard models were employed to calculate the adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for lung cancer incidence up to 2019. RESULTS: In multivariate analysis, group 2 exhibited a 26% higher risk of developing lung cancer than group 1 (HR, 1.26; 95% CI, 1.19 to 1.35). Furthermore, group 3 demonstrated a 72% elevated risk of lung cancer relative to group 1 (HR, 1.72; 95% CI, 1.58 to 1.89). Among participants with dipstick proteinuria of 2+ or greater, group 3 faced a significantly higher risk of lung cancer than group 1 (HR, 2.93; 95% CI, 1.37 to 6.24). CONCLUSIONS Low eGFR was significantly associated with increased lung cancer risk within the Korean population. A particularly robust association was observed in individuals with severe proteinuria, emphasizing the need for further investigation.

Background/Aims: Coronavirus disease 2019 (COVID-19) is associated with acute respiratory syndrome. The mechanisms underlying the different degrees of pneumonia severity in patients with COVID-19 remain elusive. This study provides evidence that COVID-19 is associated with eosinophil-mediated inflammation. Methods: We performed a retrospective case series of three patients with laboratory and radiologically confirmed COVID-19 pneumonia admitted to Chosun University Hospital. Demographic and clinical data on inflammatory cell lung infiltration and cytokine levels in patients with COVID-19 were collected. Results: Cytological analysis of sputum, tracheal aspirates, and bronchoalveolar lavage fluid (BALF) samples from all three patients revealed massive infiltration of polymorphonuclear cells (PMNs), such as eosinophils and neutrophils. All sputum and BALF specimens contained high levels of eosinophil cationic proteins. The infiltration of PMNs into the lungs, together with elevated levels of natural killer T (NKT) cells in BALF and peripheral blood samples from patients with severe pneumonia in the acute phase was confirmed by flow cytometry. Conclusions These results suggest that the lungs of COVID-19 patients can exhibit eosinophil-mediated inflammation, together with an elevated NKT cell response, which is associated with COVID-19 pneumonia.

BACKGROUND: Lower-limb varicose veins (VVs) are common and known to have a higher prevalence among people who work in occupations requiring prolonged standing. In the Republic of Korea, however, VV-related occupational factors have seldom been examined. This study was conducted to assess the prevalence of VVs among nurses, an occupational group considered to be at high risk of VVs, and determine the occupational risk factors of prolonged standing. METHODS: Between March and August 2014, a questionnaire survey coupled with Doppler ultrasonography was conducted on the nurses working at a university hospital. RESULTS: A total of 414 nurses participated in the survey and diagnostic testing. From the survey analysis and test results, the prevalence of VVs in nurses was estimated to be 16.18%. Significant factors for venous reflux were age [odds ratio (OR) = 1.06, 95% confidence interval (CI) = 1.03–1.10], pregnancy (OR = 2.15, 95% CI = 1.17–3.94), and delivery (OR = 2.02, 95% CI = 1.08–3.78). The statistical significance of these factors was verified after risk adjustment for sociodemographic factors (OR = 3.40, 95% CI = 1.27–9.09). CONCLUSION: Factors significantly associated with venous reflux were increasing age and prolonged working hours (≥ 4 hours) in a standing position (OR = 2.80, 95% CI = 1.08–7.25), even after risk adjustment for sociodemographic factors. This study is significant in that an objective diagnosis of VVs preceded the analysis of the risk factors for VV incidence, thus verifying objectively that VVs are associated with occupations requiring prolonged hours of working in a standing position.
Diagnosis ; Diagnostic Tests, Routine ; Humans ; Incidence ; Occupational Groups ; Occupations ; Posture ; Pregnancy ; Prevalence* ; Republic of Korea ; Risk Adjustment ; Risk Factors* ; Ultrasonography, Doppler ; Varicose Veins*

STUDY DESIGN: Survey based study. PURPOSE: To assess the degree of agreement in level selection of laminoplasty (LP) for the selected cervical myeloradiculopathy cases between experienced spine surgeons. OVERVIEW OF LITERATURE: Although, cervical LP is a widely used surgical technique for multi-level spinal cord compression, until now there is no consensus about how many segments or which segments should be opened to achieve a satisfactory decompression. METHODS: Thorough clinical and radiographic data (plain X-ray, computed tomography, and magnetic resonance imaging) of 30 patients who had cervical myelopathy were prepared. The data were provided to three independent spine surgeons with over 10 years experience in operation of their own practices. They were questioned about the most preferable surgical method and suitable decompression levels. The second survey was carried out after 6 months with the same cases. If the level difference between respondents was a half level or below, agreement was considered acceptable. The intraobserver and interobserver agreements in level selection were assessed by kappa statistics. RESULTS: Three respondents selected LP as an option for 6, 8, and 22 cases in the first survey and 10, 21, and 24 cases in the second survey. The reasons for selection of LP were levels of ossification of the posterior longitudinal ligament (p=0.004), segmental kyphotic deformity (p=0.036) and mean compression score (p=0.041). Intraobserver agreement showed variable results. Interobserver agreement was poor to fair by perfect matching (kappa=0.111–0.304) and fair to moderate by acceptable matching (kappa=0.308–0.625). CONCLUSIONS: The degree of agreement for level selection of LP was not high even though experienced surgeons would choose the opening segments on the basis of same criteria. These results suggest that more specific guidelines in determination of levels for LP should be required to decrease unnecessary wide decompression according to individual variance.
Cervical Vertebrae ; Congenital Abnormalities ; Consensus ; Decompression ; Female ; Humans ; Laminoplasty* ; Longitudinal Ligaments ; Methods ; Spinal Cord Compression ; Spinal Cord Diseases ; Spine ; Surgeons* ; Surveys and Questionnaires

Immunoglobulin G4-related sclerosing disease (IgG4-RD) is histologically a chronic inflammatory disorder characterized by infiltration of lymphoplasmacytes, sclerosis, and an elevated serum level of IgG4 and IgG4 positive plasmocytes. IgG4-RD is associated with autoimmune pancreatitis, sclerosing cholangitis, sialalithiasis, retroperitoneal diseases, inflammatory arotitis and Mikulicz's disease, typically including the lacrimal glands, salivary glands, pancreas, thyroid gland, lungs and kidneys. It is important to distinguish IgG4-RD from neoplastic disease as it responses well to steroid. Because consensus for nomenclature of IgG4-RD is recently made, reports of IgG4-RD in the Head and Neck area are still rare. In the first case, a 68-year-old man presented with a recurring submandibular gland mass from 7 years ago; he underwent submandibular gland resection and was diagnosed as IgG4-RD. In the second case, a 69-year-old mass presented with a relapsing right neck mass on level Ib. He underwent an exsional biopsy and was diagnosed with the same disease entity. We experienced two cases of IgG4-RD, and so report them with a brief literature review.
Aged ; Biopsy ; Cholangitis, Sclerosing ; Consensus ; Head ; Humans ; Immunoglobulin G ; Immunoglobulins* ; Kidney ; Lacrimal Apparatus ; Lung ; Neck ; Pancreas ; Pancreatitis ; Salivary Glands ; Sclerosis ; Submandibular Gland ; Thyroid Gland

The aberrant or ectopic thyroid in lateral neck is a rare developmental anomaly. Furthermore, the primary thyroid carcinoma arising in ectopic thyroid is extremely rare, only a few cases have been reported so far in English literature. We report a 64-year-old male with left transglottic cancer and primary papillary carcinoma from lateral aberrant thyroid in left lateral neck. Preoperatively, we diagnosed as transglottic cancer with ipsilateral neck metastasis. The patient underwent total laryngectomy, left selective neck dissection and left thyroidectomy. Finally, the patient was diagnosed as left transglottic cancer and papillary carcinoma from lateral aberrant thyroid. Surgeons should take into account a primary ectopic thyroid carcinoma arising in lateral neck may co-exist with another type of head and neck tumor.
Carcinoma, Papillary ; Head ; Humans ; Laryngeal Neoplasms* ; Laryngectomy ; Larynx* ; Male ; Middle Aged ; Neck ; Neck Dissection ; Neoplasm Metastasis* ; Thyroid Dysgenesis ; Thyroid Gland* ; Thyroid Neoplasms* ; Thyroidectomy

Cryptococcus is an encapsulated, yeast-like fungus that rarely causes infection in immunocompetent patients. We present the case report of a 66-year-old female patient with a history of rectal cancer with an isolated lumbar vertebral cryptococcosis proven by biopsy performed during operation. The patient was not an immunocompromised host and did not have any other risk factors except the history of cured rectal cancer. The presumptive diagnosis based on imaging studies was metastatic spine cancer, so operation was performed. However, cryptococcal osteomyelitis was diagnosed in the pathologic examination. This case report emphasizes that we should be aware that lumbar cryptococcosis can be a rare cause of mimicking lesions with metastatic cancer.
Aged ; Biopsy ; Cryptococcosis ; Cryptococcus ; Diagnosis ; Female ; Fungi ; Humans ; Immunocompromised Host ; Lumbar Vertebrae ; Neoplasm Metastasis ; Osteomyelitis* ; Rectal Neoplasms ; Risk Factors ; Spine

STUDY DESIGN: A case report. OBJECTIVES: To report the case of a patient whose preoperative imaging results seemed to show metastatic spine tumor but who actually had a vertebral pathologic fracture caused by spine tuberculosis. SUMMARY OF LITERATURE REVIEW: Tuberculosis spondylitis is classified into peridiscal, central, anterior, and posterior spondylitis according to the portion involved, and central spondylitis can be mistaken as a tumor. MATERIALS AND METHODS: Imaging studies were performed in a 79-year-old female with progressive lower extremity weakness. We found a T12 pathologic vertebral fracture, which was suspected to be metastatic cancer. RESULTS: We performed surgery and found spine tuberculosis in the pathological and immunological examinations. Two weeks postoperatively, the patient could walk with crutches and underwent anti-tuberculosis therapy. CONCLUSIONS: Even when the results of imaging studies predict spinal metastasis, we should keep in mind the possibility of spinal tuberculosis.
Aged ; Crutches ; Decompression ; Female ; Fractures, Spontaneous ; Humans ; Lower Extremity ; Neoplasm Metastasis ; Spine ; Spondylitis ; Tuberculosis ; Tuberculosis, Spinal*

BACKGROUND: Metastatic pathological fractures of the spine are a major problem for cancer patients; however, there is no consensus on treatment strategy. The purpose of this study was to evaluate various treatment options by analyzing their patterns for metastatic pathological fractures of the spine. METHODS: In this study, 54 patients (male:female = 36:18) who were diagnosed with metastatic pathological fractures of spine were recruited. Demographic data, origin of cancer, type of treatment, and results were obtained from electronic medical records. Treatment options were divided into radiotherapy (RT), vertebroplasty (VP) or kyphoplasty (KP), operation (OP), and other treatments. Treatment results were defined as aggravation, no response, fair response, good response, and unknown. The survival time after detection of pathologic fractures was analyzed with the Kaplan-Meier method. RESULTS: The mean age of the patients was 62.3 years. Hepatocellular carcinoma was the most common cancer of primary origin (n = 9), followed by multiple myeloma (n = 8). RT was the most common primary choice of treatment (n = 29, 53.7%), followed by OP (n = 13, 24.1%), and VP or KP (n = 10, 18.5%). Only 13 of 29 RT cases and 7 of 13 OP cases demonstrated a fair or good response. The mean survival time following detection of pathological spinal fractures was 11.1 months for 29 patients, who died during the study period. CONCLUSIONS: RT was the most common primary choice of treatment for metastatic pathological fractures of the spine. However, the response rate was suboptimal. Although OP should be considered for the relief of mechanical back pain or neurologic symptoms, care should be taken in determining the surgical indication. VP or KP could be considered for short-term control of localized pain, although the number of cases was too small to confirm the conclusion. It is difficult to determine the superiority of the treatment modalities, hence, a common guideline for the diagnosis and treatment of metastatic pathological fractures of the spine is required.
Carcinoma, Hepatocellular/mortality/pathology ; Female ; Humans ; Liver Neoplasms/mortality/pathology ; Male ; Middle Aged ; Multiple Myeloma/mortality/pathology ; Retrospective Studies ; Spinal Fractures/etiology/mortality/*radiotherapy/*surgery ; Spinal Neoplasms/*complications/secondary ; Spine ; Treatment Outcome