Mutations in myeloid transcription factors and activated signaling genes predict chronic myeloid leukemia outcomes.

Advancements in genomics are transforming the clinical management of chronic myeloid leukemia (CML) towards precision medicine. The impact of somatic mutations on treatment outcomes is still under debate. We studied the association of somatic mutations in epigenetic modifiers genes and activated signaling/myeloid transcription factor (AS/MTF), with disease progression and treatment failure in CML patients following tyrosine kinase inhibitor (TKI) therapy. A total of 394 CML samples were sequenced, including 254 samples collected at initial diagnosis, and 140 samples taken during follow-up. Single-molecule molecular inversion probe (smMIP)-based next-generation sequencing (NGS) was conducted targeting recurrently mutated loci in 40 genes with a limit of detection of 0.2%. A total of 70 mutations were detected in 57 (22.4%) diagnostic samples, while 64 mutations were detected in 39 (27.9%) of the follow-up samples. Carrying any mutation at initial diagnosis was associated with worse outcomes following TKI therapy, particularly in AS/MTF genes. Patients having these mutations at initial diagnosis and treated with Imatinib showed higher risks of treatment failure (HR 2.53, 95% CI [1.13-5.66], p=0.0239). The adverse prognostic impact of the mutations was not clear for patients treated with second-generation TKIs (2G-TKI). The multivariate analysis affirmed that mutations in AS/MTF genes independently serve as adverse prognostic factors for molecular response, failure-free survival (FFS), and progression risk. Additionally, there was an observable non-significant trend indicating a heightened risk of progression to advanced disease and worse overall survival (OS). Conclusion: Mutations in the AS/MTF genes using smMIP-based NGS can help identify patients with a potential risk of both treatment failure and progression, even from initial diagnosis, and may help upfront TKI selection.

The online promotion strategies of e-cigarette and heated tobacco product retailers in South Korea following the COVID-19 pandemic: Implications for regulation.

INTRODUCTION: The surge in popularity of e-cigarettes and heated tobacco products (HTPs) in South Korea, driven by perceived health benefits and COVID-19-related concerns, has led to increased advertising claims about their safety despite ongoing debates about their health effects. This study explores the marketing strategies of online e-cigarette and HTP retailers in South Korea pre- and post-COVID-19, examining potential misleading claims and providing a foundation for future regulatory measures. METHODS: We conducted a comprehensive study of eight major e-commerce platforms and three dominant search engines in South Korea to analyze the marketing and advertising strategies of e-cigarettes and heated tobacco products (HTPs) (n=774). Using specific keywords, promotional strategies were identified and categorized, after which statistical analysis was conducted to understand the frequency and proportion of these strategies, highlighting differences between HTP and e-cigarette sellers. RESULTS: Our analysis reveals a significant rise in the number of online retailers selling e-cigarettes and HTPs following the COVID-19 pandemic, with the promotional strategies 'Stay home and vape' and 'Trendy' being the most prevalent. Trends also indicate a shift in promotional strategies over the years, with a marked increase in health reassurance themes and appeals to trendiness, particularly targeting female consumers, which were used significantly more at HTPs stores. CONCLUSIONS: The study highlights the need for stricter regulation due to the potential health risks posed by the aggressive marketing strategies of e-cigarette and HTP online retailers in South Korea, amplified by the COVID-19 pandemic.

Probiotic Lactiplantibacillus plantarum KU210152 and its fermented soy milk attenuates oxidative stress in neuroblastoma cells.

We evaluated the probiotic properties and neuroprotective effects of Lactiplantibacillus plantarum KU210152 and its application in soy milk. L. plantarum KU210152 exhibited high tolerance to artificial gastrointestinal conditions, high adhesion to intestinal cells (HT-29), and safe enzyme production. Conditioned medium acquired from HT-29 cells treated with heat-killed lactic acid bacteria (LAB-CM) was used to evaluate the neuroprotective effects. The CM exhibited neuroprotective effects via cell viability assay, morphological observations, and suppression of ROS production. Heat-killed L. plantarum KU210152 increased brain-derived neurotrophic factor (BDNF) and tyrosine hydroxylase (TH) expression in HT-29 cells. In SH-SY5Y cells, pretreatment with L. plantarum KU210152 CM decreased Bax/Bcl-2 ratio and upregulated BDNF and TH expression. The CM inhibited caspase-9 and caspase-3 activities. The neuroprotective effects of L. plantarum KU210152 were also confirmed in fermented soy milk. Therefore, both L. plantarum KU210152 and the fermented soy milk can be used as functional ingredients with neuroprotective effects against oxidative stress.

International and national frameworks, guidelines, recommendations, and strategies for maternal tobacco prevention and cessation: A scoping review protocol.

Tobacco use during and around pregnancy can significantly increase the risk of stillbirth, congenital disabilities, premature birth, and low-weight birth. To establish maternal tobacco prevention and cessation frameworks for primary care and dental providers and to facilitate cross-national learning, this scoping review aims: 1) to analyze the body of literature on maternal tobacco prevention and cessation frameworks, guidelines, recommendations, and strategies at the international and national level; 2) to identify common core elements; and 3) to identify gaps in the literature, and propose future initiatives and policy development directions. A systematic database search based on the JBI methodology and corresponding PRISMA-ScR guidelines will be conducted from January 2015 to August 2023. Searches in different databases will be combined with an expert survey among the members of the World Federation of Public Health Associations (WFPHA) - Oral Health, Tobacco Control, and the Women, Adolescent, and Children's Working Groups to evaluate the search outcomes and add maternal tobacco prevention and cessation frameworks, guidelines, recommendations, or strategies. Using a systematic review tool to support the screening, two independent reviewers will screen the titles and abstracts of all articles, in order to include the relevant ones for full-text screening, and an independent third author will resolve conflicts, if there is any discrepancy between the two independent reviewers' search. After a full-text review, data extraction will be conducted for analysis. Descriptive analyses include the publication year, country, legal quality, and target group addressed. A narrative synthesis will describe the scope and content of the frameworks, guidelines, recommendations, and strategies. The scoping review will serve as a stepping-stone to creating a WFPHA policy resolution on tobacco prevention and cessation framework for women of childbearing age led by the WFPHA Oral Health, Tobacco Control and the Women, Adolescent, and Children's Working Group members. This WFPHA policy resolution 'Maternal Tobacco Cessation and Prevention Recommendations for Primary Care Providers and Dental Providers' will be forwarded to the WFPHA General Council and the General Assembly for approval and will be disseminated to the WFPHA public health association members. Ultimately, this recommendation will be used by each national public health association to consider integrating it into their maternal health strategy.

Effect of Vitamin B12 Replacement Intervals on Clinical Symptoms and Laboratory Findings in Gastric Cancer Patients after Total Gastrectomy.

The management of patients with vitamin B12 deficiency after total gastrectomy (TG) remains controversial. We aimed to evaluate the effect of vitamin B12 replacement intervals on the clinical characteristics in these patients. The data from patients who received vitamin B12 supplementation after TG between 2007 and 2018 at the National Cancer Center, Korea, were retrospectively evaluated. Vitamin B12 deficiency was defined as a serum vitamin B12 level of <200 pg/mL or urine methylmalonic acid level > 3.8 mg/gCr. The patients were divided into a regular replacement group (patients received an intramuscular injection or oral medication regularly), and a lab-based replacement group (patients received vitamin B12 intermittently after checking the level). The symptoms and biochemical parameters were compared between these groups. The regular and lab-based replacement groups included 190 and 216 patients, respectively. The median vitamin B12 replacement intervals were 1 and 9 months, respectively (p < 0.001). After replacement, the regular replacement group had higher vitamin B12 levels than the lab-based replacement group (p < 0.001). However, the serum hemoglobin level showed no significant changes. After replacement, there was no significant difference in the proportion of the symptomatic patients between the groups. Replacing vitamin B12 with a lab-based protocol may be sufficient for TG patients.

Immune Regulatory Function of Cancer- Associated Fibroblasts in Non-small Cell Lung Cancer.

BACKGROUND: Cancer-associated fibroblasts (CAFs) are key components of the tumor microenvironment and significantly contribute to immune evasion. We investigated the effects of CAFs on the immune function of CD4+ and CD8+ T cells in non-small cell lung cancer (NSCLC). METHODS: We isolated CAFs and normal fibroblasts (NFs) from tumors and normal lung tissues of NSCLC patients, respectively. CAFs were co-cultured with activated T cells to evaluate their immune regulatory function. We investigated the effect of CAF conditioned medium (CAF-CM) on the cytotoxicity of T cells. CAFs were also co-cultured with activated peripheral blood mononuclear cells and further incubated with cyclooxygenase- 2 (COX2) inhibitors to investigate the potential role of COX2 in immune evasion. RESULTS: CAFs and NFs were isolated from the lung tissues (n=8) and lymph nodes (n=3) of NSCLC patients. Immune suppressive markers, such as COX2 and programmed death-ligand 1 (PD-L1), were increased in CAFs after co-culture with activated T cells. Interestingly, CAFs promoted the expression of programmed death-1 in CD4+ and CD8+ T cells, and strongly inhibited T cell proliferation in allogenic and autologous pairs of CAFs and T cells. CAF-CM decreased the cytotoxicity of T cells. COX2 inhibitors partially restored the proliferation of CD4+ and CD8+ T cells, and downregulated the expression of COX2, prostaglandin E synthase, prostaglandin E2, and PD-L1 in CAFs. CONCLUSION: CAFs promote immune evasion by suppressing the function of CD4+ and CD8+ T cells via their effects on COX2 and PD-L1 in NSCLC. The immunosuppressive function of CAFs could be alleviated by COX2 inhibitors.

Quality Characteristics of Sweet Potato Jelly Prepared Using the Enzymatic Saccharification Method.

In this study, jelly was prepared using saccharified sweet potatoes without sugar, and its quality characteristics were compared according to the sweet potato cultivar. Three sweet potato varieties, namely Juwhangmi (orange color), Sinjami (purple color), and Daeyumi (yellow flesh color), were used. The total free sugar and glucose contents of the hydrolysate were found to increase during the enzyme treatment. However, no differences in the moisture, total soluble solids, or textural properties were found among the sweet potato cultivars. Sinjami had high total polyphenol and flavonoid contents of 446.14 mg GAE/100 g and 243.59 mg CE/100 g, respectively, and it had the highest antioxidant activity among the cultivars. Based on the sensory evaluation, an overall preference appeared in the order of Daeyumi, Sinjami, and Juwhangmi cultivars. This result shows that jelly can be manufactured by saccharifying sweet potatoes, and it was confirmed that the characteristics of raw sweet potatoes had a great influence on the quality characteristics of the jelly. Further, the characteristics of raw sweet potatoes had a remarkable influence on the quality characteristics of the jelly.

Mycosis fungoides and Sézary syndrome.

Mycosis fungoides (MF) and Sézary syndrome (SS) are a distinct disease entity of cutaneous T-cell lymphoma with heterogenous clinical features and prognosis. MF mainly involves skin and usually shows an indolent and favorable clinical course. In patients with advanced-stage disease, extracutaneous involvement including lymph nodes, viscera, and blood, or large cell transformation may be observed. SS is a leukemic form of advanced-stage MF, characterized by generalized erythroderma. Early-stage MF can be treated with skin-directed therapy. However, patients with refractory or advanced-stage disease are associated with severe symptoms or poor prognosis, requiring systemic therapy. Recent progress in understanding the pathogenesis of MF/SS has contributed to advances in the management of these rare diseases. This review aims to describe the clinical manifestations, diagnosis, risk stratification, and treatment strategy of MF/SS, focusing on the recent updates in the management of these diseases.

Computed tomographic features of focal lipogranulomatous lymphangitis for differentiating from malignant intestinal lesions in a dog.

An eight-year-old Maltese dog presented with diarrhea and anorexia. Ultrasonography revealed marked focal wall thickening with loss of layering in the distal ileum. Contrast-enhanced computed tomography (CT) revealed a preserved wall layer with hypoattenuating middle wall thickening. In some segments of the lesion, small nodules protruding toward the mesentery from the outer layer were observed. Histopathology revealed focal lipogranulomatous lymphangitis (FLL) with lymphangiectasia. This is the first report to describe the CT features of FLL in a dog. CT features of preserved wall layers with hypoattenuating middle wall thickening and small nodules can assist in diagnosing FLL in dogs.

Neuroprotective Effects of Ecklonia cava in a Chronic Neuroinflammatory Disease Model.

Inflammation is a natural defense mechanism against noxious stimuli, but chronic inflammation can lead to various chronic diseases. Neuroinflammation in the central nervous system plays an important role in the development and progression of neurodegenerative diseases. Polyphenol-rich natural products, such as Ecklonia cava (E. cava), are known to have anti-inflammatory and antioxidant properties and can provide treatment strategies for neurodegenerative diseases by controlling neuroinflammation. We investigated the effects of an E. cava extract on neuroinflammation and neurodegeneration under chronic inflammatory conditions. Mice were pretreated with E. cava extract for 19 days and then exposed to E. cava with lipopolysaccharide (LPS) for 1 week. We monitored pro-inflammatory cytokines levels in the serum, inflammation-related markers, and neurodegenerative markers using Western blotting and qRT-PCR in the mouse cerebrum and hippocampus. E. cava reduced pro-inflammatory cytokine levels in the blood and brain of mice with LPS-induced chronic inflammation. We also measured the activity of genes related to neuroinflammation and neurodegeneration. Surprisingly, E. cava decreased the activity of markers associated with inflammation (NF-kB and STAT3) and a neurodegenerative disease marker (glial fibrillary acidic protein, beta-amyloid) in the cerebrum and hippocampus of mice. We suggest that E. cava extract has the potential as a protective agent against neuroinflammation and neurodegenerative diseases.

Clonal hematopoiesis in the donor does not adversely affect long-term outcomes following allogeneic hematopoietic stem cell transplantation: result from a 13-year follow-up.

Donor clonal hematopoiesis may be transferred to the recipient through allogeneic hematopoietic stem cell transplantation (HSCT), but the potential for adverse long-term impact on transplant outcomes remains unknown. A total of 744 samples from 372 recipients who received HSCT and the corresponding donors were included. Bar-coded error-corrected sequencing using a modified molecular inversion probe capture protocol was performed, which targeted 33 genes covering mutations involved in clonal hematopoiesis with indeterminate potential (CHIP) and other acute myeloid leukemia-related mutations. A total of 30 mutations were detected from 25 donors (6.7%): the most frequently mutated gene was TET2 (n=7, 28%), followed by DNMT3A (n=4, 16%), SMC3 (n=3, 12%) and SF3B1 (n=3, 12%). With a median follow-up duration of 13 years among survivors, the presence of CHIP in the donor was not associated with recipient overall survival (P=0.969), relapse incidence (P=0.600) or non-relapse mortality (P=0.570). Donor CHIP did not impair neutrophil (P=0.460) or platelet (P=0.250) engraftment, the rates of acute (P=0.490), or chronic graft-versus-host disease (P=0.220). No significant difference was noted for secondary malignancy following HSCT between the two groups. The present study suggests that the presence of CHIP in allogeneic stem donors does not adversely affect transplant outcomes after HSCT. Accordingly, further study is warranted to reach a clearer conclusion on whether molecular profiling to determine the presence of CHIP mutations is necessary for the pretransplant evaluation of donors prior to stem cell donation.

Influence of Nonalcoholic Fatty Liver Disease With Increased Liver Enzyme Levels on the Risk of Cirrhosis and Hepatocellular Carcinoma.

BACKGROUND & AIMS: The influence of nonalcoholic fatty liver disease (NAFLD) on the long-term risk of cirrhosis and hepatocellular carcinoma (HCC) in Asian populations has not been widely investigated. METHODS: We enrolled 129,374 adults aged 30 years and older, all of whom participated in a health screening program from 2008 through 2013, were seronegative for hepatitis B surface antigen and anti-hepatitis C virus antibodies, and had limited daily alcohol consumption (<20 g/d for men and <10 g/d for women). Abdominal ultrasonography was performed to determine the presence of NAFLD. The participants were divided into the following groups: NAFLD with increased or normal liver enzyme levels, and non-NAFLD with normal liver enzyme levels. The incidences of cirrhosis and HCC were determined through computerized data linkage with nationwide registries. Cox proportional hazard models were used to estimate the hazard ratios of NAFLD on the risks of cirrhosis and HCC. RESULTS: The incidence rates of cirrhosis and HCC increased as follows: non-NAFLD with normal liver enzyme levels (n = 66,801; 51%), NAFLD with normal liver enzyme levels (n = 41,461; 32%), and NAFLD with increased liver enzyme levels (n = 21,112; 16%). In the NAFLD group with increased liver enzyme levels and the NAFLD group with normal liver enzyme levels, the corresponding multivariate-adjusted hazard ratios for cirrhosis were 3.51 (95% confidence interval [CI]: 2.36-5.22) and 0.73 (95% CI: 0.46-1.16), and for HCC were 1.91 (95% CI: 1.08-3.38) and 0.57 (95% CI: 0.31-1.04), respectively, compared with the non-NAFLD group (P for trend < .001). The findings were consistent after restricting the analysis to nonobese individuals (body mass index, <25 kg/m2) and nonobese individuals without diabetes (P < .05). CONCLUSIONS: Individuals with NAFLD and increased liver enzyme levels showed significantly higher risks for cirrhosis and HCC and should be monitored.

Equilibria of semi-volatile isothiazolinones between air and glass surfaces measured by gas chromatography and Raman spectroscopy.

Trace amounts of semi-volatile organic compounds (SVOCs) of the two isothiazolinones of 2-methylisothiazol-3(2H)-one (MIT) and 2-octyl-4-isothiazolin-3-one (OIT) were detected both in the air and on glass surfaces. Equilibria of SVOCs between air and glass were examined by solid phase microextraction-gas chromatography/mass spectrometry (SPME-GC/MS). Surface to air distribution ratios of Ksa for MIT and OIT were determined to be 5.10 m and 281.74 m, respectively, suggesting more abundant MIT in the gas phase by a factor of ∼55. In addition, a facile method of silver nanocube (AgNC)-assisted surface-enhanced Raman scattering (SERS) has been developed for the rapid and sensitive detection of MIT and OIT on glass surfaces. According to MIT and OIT concentration-correlated SERS intensities of Raman peaks at ∼1585 cm-1 and ∼1125 cm-1, respectively. Their calibration curves have been obtained in the concentration ranges between 10-3 to 10-10 M and 10-3 to 10-11 M with their linearity of 0.9986 and 0.9989 for MIT and OIT, respectively. The limits of detection (LODs) of the two isothiazolinones were estimated at 10-10 M, and 10-11 M for MIT and OIT, respectively. Our results indicate that AgNC-assisted SERS spectra are a rapid and high-ultrasensitive method for the quantification of MIT and OIT in practical applications. The development of analytical methods and determination of the Ksa value obtained in this study can be applied to the prediction of the exposure to MIT and OIT from various chemical products and dynamic behaviors to assess human health risks in indoor environments.

Pretreatment C-reactive protein-to-albumin ratio predicts clinical outcomes in patients with peripheral T-cell lymphoma.

PURPOSE: Peripheral T-cell lymphoma (PTCL) is an aggressive and heterogenous T-cell lymphoid malignancy. The prognostic value of C-reactive protein-to-albumin ratio (CAR) has never been assessed in PTCL. MATERIALS AND METHODS: This study retrospectively reviewed the medical records of 76 patients diagnosed with various subtypes of PTCL. A CAR cutoff value of 0.794 was determined, and clinical outcomes, including response rate, overall survival (OS), and progression-free survival (PFS), were compared between the high (> 0.794) and low (≤ 0.794) CAR groups. RESULTS: After induction therapy, complete response was achieved in 8 (32.0%) and 39 patients (76.5%) in the high and low CAR groups, respectively. During the median follow-up of 57.5 months, the high CAR group had significantly worse 5-year PFS and 5-year OS rates. Even with adjustment for the International Prognostic Index (≥ 3), Prognostic Index for PTCL-unspecified (≥ 3), and T cell score (≥ 2), high CAR remained a significant prognostic factor for PFS (hazard ratio [HR]: 4.01, 95% confidence interval [CI] 2.04-7.86, p < 0.001) and OS (HR: 2.97, 95% CI: 1.33-6.64, p = 0.008). CONCLUSION: CAR may play a complementary role in predicting prognosis in patients with PTCL, considering its simplicity, objectivity, and easy accessibility.

Single cell proteogenomic sequencing identifies a relapse-fated AML subclone carrying FLT3-ITD with CN-LOH at chr13q.

Internal tandem duplication of the Feline McDonough Sarcoma (FMS)-like tyrosine kinase 3 (FLT3-ITD) is one of the most clinically relevant mutations in acute myeloid leukemia (AML), with a high FLT3-ITD allelic ratio (AR) (≥0.5) being strongly associated with poor prognosis. FLT3-ITDs are heterogeneous, varying in size and location, with some patients having multiple FLT3-ITDs. Bulk cell-based approaches are limited in their ability to reveal the clonal structure in such cases. Using single-cell proteogenomic sequencing (ScPGseq), we attempted to identify a relapse-fated subclone in an AML case with mutations in WT1, NPM1, and FLT3 tyrosine kinase domain and two FLT3-ITDs (21 bp and 39 bp) (low AR) at presentation, then relapsed only with WT1 and NPM1 mutations and one FLT3-ITD (high AR). This relapse-fated subclone at presentation (∼2.1% of sequenced cells) was characterized by the presence of a homozygous 21 bp FLT3-ITD resulting from copy neutral loss of heterozygosity (CN-LOH) of chr13q and an aberrant, immature myeloid cell surface signature, contrast to the cell surface phenotype at presentation. In contrast to results from multicolor flow-cytometry, ScPGseq not only enabled the early detection of rare relapse-fated subclone showing immature myeloid signature but also highlighted the presence of homozygous 21 bp FLT3-ITDs in the clone at presentation.

Cohort Profile: Korean Tuberculosis and Post-Tuberculosis Cohort Constructed by Linking the Korean National Tuberculosis Surveillance System and National Health Information Database.

We aimed to review the current data composition of the Korean Tuberculosis and Post-Tuberculosis Cohort, which was constructed by linking the Korean Tuberculosis Surveillance System (KNTSS; established and operated by the Korean Disease Control and Prevention Agency since 2000) and the National Health Information Database (NHID; established by the National Health Insurance Service in 2012). The following data were linked: KNTSS data pertaining to patients diagnosed with tuberculosis between 2011 and 2018, NHID data of patients with a history of tuberculosis and related diseases between 2006 and 2018, and data (obtained from the Statistics Korea database) on causes of death. Data from 300 117 tuberculosis patients (177 206 men and 122 911 women) were linked. The rate of treatment success for new cases was highest in 2015 (86.7%), with a gradual decrease thereafter. The treatment success rate for previously treated cases showed an increasing trend until 2014 (79.0%) and decreased thereafter. In total, 53 906 deaths were confirmed among tuberculosis patients included in the cohort. The Korean Tuberculosis and Post-Tuberculosis Cohort can be used to analyze different measurement variables in an integrated manner depending on the data source. Therefore, these cohort data can be used in future epidemiological studies and research on policy-effect analysis, treatment outcome analysis, and health-related behaviors such as treatment discontinuation.

Curcumae Radix Decreases Neurodegenerative Markers through Glycolysis Decrease and TCA Cycle Activation.

Neurodegenerative diseases (ND) are being increasingly studied owing to the increasing proportion of the aging population. Several potential compounds are examined to prevent neurodegenerative diseases, including Curcumae radix, which is known to be beneficial for inflammatory conditions, metabolic syndrome, and various types of pain. However, it is not well studied, and its influence on energy metabolism in ND is unclear. We focused on the relationship between ND and energy metabolism using Curcumae radix extract (CRE) in cells and animal models. We monitored neurodegenerative markers and metabolic indicators using Western blotting and qRT-PCR and then assessed cellular glycolysis and metabolic flux assays. The levels of Alzheimer's disease-related markers in mouse brains were reduced after treatment with the CRE. We confirmed that neurodegenerative markers decreased in the cerebrum and brain tumor cells following low endoplasmic reticulum (ER) stress markers. Furthermore, glycolysis related genes and the extracellular acidification rate decreased after treatment with the CRE. Interestingly, we found that the CRE exposed mouse brain and cells had increased mitochondrial Tricarboxylic acid (TCA) cycle and Oxidative phosphorylation (OXPHOS) related genes in the CRE group. Curcumae radix may act as a metabolic modulator of brain health and help treat and prevent ND involving mitochondrial dysfunction.

Accuracy of Noninvasive Scoring Systems in Assessing Liver Fibrosis in Patients with Nonalcoholic Fatty Liver Disease: A Systematic Review and Meta-Analysis.

Background/Aims: Several noninvasive scoring systems have been developed to determine the risk of advanced fibrosis in nonalcoholic fatty liver disease (NAFLD). We examined the diagnostic accuracy of the fibrosis-4 (FIB-4) score and NAFLD fibrosis score (NFS) in patients with biopsy-proven NAFLD. Methods: For this meta-analysis, various databases including PubMed (MEDLINE), EMBASE, OVID Medline and the Cochrane Library were systematically searched. After the acquired abstracts were reviewed by two investigators, manuscripts were chosen for a full-text examination. Results: Thirty-six studies evaluating biopsy-proven NAFLD were selected for meta-analysis. A total of 14,992 patients were analyzed. The lower cutoff sensitivity of the FIB-4 score predicting histological fibrosis stage 3 or more (≥F3) was 69%, with specificity of 64%, positive likelihood ratio (LR+) of 1.96, and negative likelihood ratio (LR-) of 0.47. The low baseline sensitivity of the NFS score predicting ≥F3 was 70%, with a specificity of 61%, LR+ of 1.83, and LR- of 0.48. The area under the receiver operating characteristic curve (AUC) values of the FIB-4 score predicting ≥F3 and ≥F2 were 76% and 68%, respectively. The AUC values of the NFS score predicting ≥F3 and ≥F2 were 74% and 60%, respectively. Conclusions: The FIB-4 or NFS test can be used to predict the degree of liver fibrosis in NAFLD, and the diagnostic accuracy resulted as relatively high in fibrosis stages of F3 or higher.

Influence of creatinine levels on survival in patients with veno-occlusive disease treated with defibrotide.

BACKGROUND/AIMS: Veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) is one of the most fatal complications of hematopoietic cell transplantation (HCT), and defibrotide is the only curative drug. We conducted this study to confirm the survival rate of VOD/SOS patients diagnosed in Korea and assess the efficacy of defibrotide. METHODS: Patients diagnosed with VOD/SOS after allogenic HCT between 2003 and 2020 were enrolled. We investigated day +100 survival rates and associated risk factors in patients who satisfied the modified Seattle criteria within 50 days of HCT. RESULTS: A total of 110 patients satisfied the modified Seattle criteria, of which 65.5% satisfied the Baltimore criteria. Thirty-seven patients were treated with defibrotide. The day +100 survival rate of the 110 patients was 65.3%. The survival rates in patients who did not meet the Baltimore criteria and in those who did were 86.8% and 53.7%, respectively (p = 0.001). The day +100 survival rate of patients treated with defibrotide was 50.5%. Among the patients receiving defibrotide, those whose creatinine levels were more than 1.2 times the baseline had a significantly lower survival rate at 26.7% (p = 0.014). On multivariate regression analysis, the hazard ratio of satisfaction of the Baltimore criteria was 4.54 (95% confidence interval [CI], 1.69 to 12.21; p = 0.003). In patients treated with defibrotide, the hazard ratio was 8.70 (95% CI, 2.26 to 33.45; p = 0.002), when creatinine was more than 1.2 times the baseline on administration. CONCLUSION: The day +100 survival rate was significantly lower when the Baltimore criteria were satisfied, and when there was an increase in creatinine at the time of defibrotide administration.

Shared Genetic Background between Parkinson's Disease and Schizophrenia: A Two-Sample Mendelian Randomization Study.

Background and objectives: Parkinson's disease (PD) and schizophrenia often share symptomatology. Psychotic symptoms are prevalent in patients with PD, and similar motor symptoms with extrapyramidal signs are frequently observed in antipsychotic-naïve patients with schizophrenia as well as premorbid families. However, few studies have examined the relationship between PD and schizophrenia. We performed this study to evaluate whether genetic variants which increase PD risk influence the risk of developing schizophrenia, and vice versa. Materials and Methods: Two-sample Mendelian randomization (TSMR) with summary statistics from large-scale genome-wide association studies (GWAS) was applied. Summary statistics were extracted for these instruments from GWAS of PD and schizophrenia; Results: We found an increase in the risk of schizophrenia per one-standard deviation (SD) increase in the genetically-predicted PD risk (inverse-variance weighted method, odds ratio = 1.10; 95% confidence interval, 1.05-1.15; p = 3.49 × 10-5). The association was consistent in sensitivity analyses, including multiple TSMR methods, analysis after removing outlier variants with potential pleiotropic effects, and analysis after applying multiple GWAS subthresholds. No relationships were evident between PD and smoking or other psychiatric disorders, including attention deficit hyperactivity disorder, autism spectrum disorder, bipolar affective disorder, major depressive disorder, Alzheimer's disease, or alcohol dependence. However, we did not find a reverse relationship; genetic variants increasing schizophrenia risk did not alter the risk of PD; Conclusions: Overall, our findings suggest that increased genetic risk of PD can be associated with increased risk of schizophrenia. This association supports the intrinsic nature of the psychotic symptom in PD rather than medication or environmental effects. Future studies for possible comorbidities and shared genetic structure between the two diseases are warranted.