Glycaemic Status and Risk of Abdominal Aortic Aneurysm: A Nationwide Cohort Study of Four Million Adults using Korean National Health Screening Data.

OBJECTIVE: This retrospective cohort study aimed to confirm the previously reported inverse association between diabetes mellitus (DM) and abdominal aortic aneurysm (AAA) using large population based data. It also investigated the associations between AAA with impaired fasting glucose (IFG) and new onset DM (not yet treated). METHODS: A representative dataset was obtained from the Korean National Health Insurance Service. Participants who were aged ≥ 50 years and received a national health examination in 2009 were included and followed until 31 December 2019. Glycaemic status was defined based on fasting plasma glucose level and the relevant diagnostic codes. AAA was ascertained using records of medical facility usage with relevant diagnostic codes or aneurysm repair surgery. A Cox proportional hazards model was used to examine the association between glycaemic status and AAA, with adjustment for confounders. Additionally, the interactions between glycaemic status and subgroups based on baseline characteristics were examined. RESULTS: The study population comprised 4 162 640 participants. Participants with IFG or DM were significantly more likely to be male, older, and have comorbidities compared with normoglycaemic participants at baseline. The incidence of AAA was lower in participants with IFG or DM compared with normoglycaemic participants. The AAA risk was lower in patients with DM than in patients with IFG, and decreased linearly according to glycaemic status: the adjusted hazard ratio was 0.88 (95% confidence interval [CI] 0.85 - 0.91) for IFG, 0.72 (95% CI 0.67 - 0.78) for newly diagnosed DM, 0.65 (95% CI 0.61 - 0.69) for DM duration < 5 years, and 0.47 (95% CI 0.44 - 0.51) for DM duration ≥ 5 years compared with the normoglycaemia group. Both IFG and DM were related to reduced AAA risk in all subgroups, suggesting an independent association. CONCLUSION: Both IFG and DM, even when not treated with antihyperglycaemic medication, were associated with a lower incidence of AAA. The AAA risk decreased linearly according to DM duration.

Assessing the Utility of Acoustic Radiation Force Impulse in the Evaluation of Non-Alcoholic Fatty Liver Disease with Severe Obesity or Steatosis.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) encompasses a heterogeneous spectrum ranging from simple steatosis to fibrosis and cirrhosis. Fibrosis, associated with long-term overall mortality and liver-related events, requires evaluation. Traditionally, liver biopsy has been the gold standard for diagnosing fibrosis. However, its invasive nature, potential complications, and sampling variability limit widespread use. Consequently, various non-invasive tests have been developed as alternatives for diagnosing fibrosis in NAFLD patients. AIM: This study aimed to compare the accuracy of non-invasive tests (NITs) and evaluate the diagnostic accuracy of acoustic radiation force impulse (ARFI), one of the point shear wave techniques, compared to conventional methods, assessing its effective role in diagnosis. METHODS: This is a retrospective study; a total of 136 patients diagnosed with fatty liver disease through ultrasonography were enrolled. The anthropometric data of the patients were collected on the day of admission and blood tests, measurements of ARFI, and a point shear test were conducted using abdominal ultrasound; a biopsy was performed the following day. In addition, we calculated the aspartate aminotransferase-to-platelet ratio index (APRI) index based on four factors (FIB-4) and the NAFLD fibrosis score (NFS). Subsequently, we assessed the diagnostic accuracy of NITs within various subgroups based on the extent of obesity, steatosis, or NAFLD activity score. RESULTS: ARFI has been shown to have the highest diagnostic value among various NITs, with AUROC values of 0.832, 0.794, 0.767, and 0.696 for ARFI, APRI, FIB-4, and NFS, respectively. In the morbidly obese subgroup, the AUROC values of ARFI, APRI, FIB-4, and NFS were 0.805, 0.769, 0.736, and 0.674. In the group with severe steatosis or non-alcoholic steatohepatitis (NASH), the AUROC values were 0.679, 0.596, 0.661, and 0.612, respectively, for severe steatosis and 0.789, 0.696, 0.751, and 0.691, respectively, for NASH. CONCLUSIONS: In conclusion, ARFI is not affected by various factors and maintains diagnostic accuracy compared to serum NITs. Therefore, we can recommend ARFI as a valuable diagnostic test to screen for advanced fibrosis in patients with NAFLD.

Efficacy comparison of high-genetic barrier nucleos(t)ide analogues in treatment-naïve chronic hepatitis B patients: a network meta-analysis.

Background/Aims: Four high-genetic barrier nucleos(t)ide analogues (NAs) for chronic hepatitis B (CHB), namely entecavir (ETV), tenofovir disoproxil fumarate (TDF), tenofovir alafenamide (TAF), and besifovir dipivoxil maleate (BSV), have been established. The aim of this study is to investigate the efficacy of four high-genetic barrier NAs using a network meta-analysis of randomized trials and propensity score-matched cohorts. Methods: Systematic search was performed using PubMed, Cochrane library, and EMBASE and included randomized controlled trials and cohort studies that used propensity score matching. Studies on treatment-naïve CHB patients treated with ETV, TDF, TAF, or BSV were included. Outcomes included alanine aminotransferase normalization and hepatitis B e antigen seroclearance at week 48 and undetectable hepatitis B virus DNA at weeks 48 and 96. Network meta-analysis was performed to synthesize the results. Results: In total, 15,000 patients from 16 studies were included. In terms of 48- and 96-week virologic response (VR), TDF outperformed ETV with statistical significance (48 weeks: odds ratio [OR], 1.38; p < 0.001; 96 weeks: OR, 1.57; p = 0.004). ETV was ranked first for 48-week biochemical response (BR) and outperformed TDF (OR, 0.76; p = 0.028). In the sensitivity analyses, 48-week VR from randomized-controlled trials were compiled, and the same trend toward the superiority of TDF over ETV was found (OR, 1.51; p = 0.030). Conclusions: Four high-genetic barrier NAs were compared, and TDF was more likely to achieve a VR after 48 weeks, while ETV provided a superior BR after 48 weeks.

Surgical Outcome of Mitral Valve Surgery in Atrial Functional Mitral Regurgitation Compared with Degenerative Etiology.

OBJECTIVE: This retrospective study analyzed the outcomes of mitral valve surgery in atrial functional mitral regurgitation (AFMR) compared with those in degenerative mitral regurgitation (DMR). METHODS: Patients with AFMR or DMR who underwent mitral valve repair/replacement at two institutions (January 2012-December 2022) were included. We excluded patients <18 years of age, undergoing concomitant cardiac surgery except for the maze procedure or tricuspid annuloplasty. We used propensity score analysis to adjust for baseline differences. RESULTS: 642 patients were enrolled. After propensity score analysis, 164 patients were classified into the DMR and 82 patients into the AFMR. All matched patients in both groups had atrial fibrillation. In DMR and AFMR, the 5-year freedom from readmission for heart failure and cardiac death was 96.3% vs. 88.6% (p = 0.045) and 100% vs. 90.0% (p = 0.002), respectively. The recurrence ratio of significant MR after mitral valve repair was not significantly different between the two groups (Log-rank = 0.699), and the 5-year freedom from MR recurrence (≥moderate) was 89.8% and 93.0%, respectively. After the maze procedure, significantly more patients in the AFMR were in junctional rhythm than in the DMR (49.1% vs. 3.3%) (p < 0.001), needing significantly more permanent pacemaker insertion during the follow-up period (11.4% vs. 1.5%, after 5 years) (Log-rank = 0.041). CONCLUSIONS: AFMR showed acceptable outcomes of mitral valve surgery, and mitral valve repair is a good treatment option. However, significantly more patients were in junctional rhythm after the maze procedure, needing more permanent pacemaker insertion.

Parental History of Memory Impairment and ß-Amyloid in Cognitively Unimpaired Older Adults.

Importance: Studies have suggested that maternal history of late-onset Alzheimer disease, but not paternal, predisposes individuals to higher brain ß-amyloid (Aß) burden, reduced brain metabolism, and lower gray matter volumes. Objective: To characterize maternal vs paternal history of memory impairment in terms of brain Aß-positron emission tomography (Aß-PET) and baseline cognition among a large sample of cognitively unimpaired older adults. Design, Setting, and Participants: This cross-sectional study leveraged data from 4413 individuals who were screened for the Anti-Amyloid Treatment in Asymptomatic Alzheimer (A4) study, a randomized clinical trial conducted across 67 sites in the US, Australia, Canada, and Japan aimed at Alzheimer disease prevention. Data were collected between April 2014 and December 2017 and analyzed from December 2022 to June 2023. Participants were cognitively unimpaired adults (Clinical Dementia Rating = 0 and/or Mini-Mental State Examination score ≥25) between the ages of 65 and 85 years who underwent PET imaging to assess cortical Aß levels for trial eligibility. A total of 4492 participants were screened, and 79 missing data were excluded. Main Outcomes and Measures: Demographic characteristics (eg, age, sex, education), apolipoprotein E genotyping, participant-reported parental history of memory impairment and parental age at symptom onset were collected as variables. Parental history was assessed in terms of continuous neocortical 18F-florbetapir Aß-PET and the Preclinical Alzheimer Cognitive Composite. Results: Of 4413 individuals (mean [SD] age, 71.27 [4.66] years, 2617 women [59.3%]), mean Aß-PET was elevated in individuals with history of memory impairment in both parents (n = 455; mean [SD] standardized uptake value ratio [SUVR] = 1.12 [0.19]; Wilcoxon P = 1.1 × 10-5) and in those with only maternal history (n = 1772; mean [SD] SUVR = 1.10 [0.19]; Wilcoxon P = 2.70 × 10-5) compared with those with only paternal history (n = 632; mean [SD] SUVR = 1.08 [0.18]; Wilcoxon P = 1.1 × 10-5) or no family history (n = 1554; mean [SD] SUVR = 1.08 [0.19]; Wilcoxon P = 1.1 × 10-5). Paternal history of early-onset memory impairment (age <65 years) but not late-onset (age ≥65 years) was associated with elevated participant Aß-PET (mean [SD] SUVR = 1.19 [0.21]; P = 3.00 × 10-6) in comparison with no paternal history (mean [SD] SUVR = 1.09 [0.19]) whereas maternal history was associated with elevated Aß in both early-onset and late-onset groups. There was no association with cognition. Conclusions and Relevance: In this study, maternal history (at any age) and paternal history of early-onset memory impairment were associated with Aß burden among asymptomatic older individuals. Sex-specific parental history may help inform clinicians on likelihood of Aß burden in offspring and help identify high-risk individuals at the earliest stages of disease for prevention.

Lipidomic Assessment of the Inhibitory Effect of Standardized Water Extract of Hydrangea serrata (Thunb.) Ser. Leaves during Adipogenesis.

Obesity is primarily exacerbated by excessive lipid accumulation during adipogenesis, with triacylglycerol (TG) as a major lipid marker. However, as the association between numerous lipid markers and various health conditions has recently been revealed, investigating the lipid metabolism in detail has become necessary. This study investigates the lipid metabolic effects of Hydrangea serrata (Thunb.) Ser. hot water leaf extract (WHS) on adipogenesis using LC-MS-based lipidomics analysis of undifferentiated, differentiated, and WHS-treated differentiated 3T3-L1 cells. WHS treatment effectively suppressed the elevation of glycerolipids, including TG and DG, and prevented a molecular shift in fatty acyl composition towards long-chain unsaturated fatty acids. This shift also impacted glycerophospholipid metabolism. Additionally, WHS stabilized significant lipid markers such as the PC/PE and LPC/PE ratios, SM, and Cer, which are associated with obesity and related comorbidities. This study suggests that WHS could reduce obesity-related risk factors by regulating lipid markers during adipogenesis. This study is the first to assess the underlying lipidomic mechanisms of the adipogenesis-inhibitory effect of WHS, highlighting its potential in developing natural products for treating obesity and related conditions. Our study provides a new strategy for the development of natural products for the treatment of obesity and related diseases.

Revised evaluation objectives of the Korean Dentist Clinical Skill Test: a survey study and focus group interviews.

PURPOSE: This study aimed to propose a revision of the evaluation objectives of the Korean Dentist Clinical Skill Test by analyzing the opinions of those involved in the examination after a review of those objectives. METHODS: The clinical skill test objectives were reviewed based on the national-level dental practitioner competencies, dental school educational competencies, and the third dental practitioner job analysis. Current and former examinees were surveyed about their perceptions of the evaluation objectives. The validity of 22 evaluation objectives and overlapping perceptions based on area of specialty were surveyed on a 5-point Likert scale by professors who participated in the clinical skill test and dental school faculty members. Additionally, focus group interviews were conducted with experts on the examination. RESULTS: It was necessary to consider including competency assessments for "emergency rescue skills" and "planning and performing prosthetic treatment." There were no significant differences between current and former examinees in their perceptions of the clinical skill test's objectives. The professors who participated in the examination and dental school faculty members recognized that most of the objectives were valid. However, some responses stated that "oromaxillofacial cranial nerve examination," "temporomandibular disorder palpation test," and "space management for primary and mixed dentition" were unfeasible evaluation objectives and overlapped with dental specialty areas. CONCLUSION: When revising the Korean Dentist Clinical Skill Test's objectives, it is advisable to consider incorporating competency assessments related to "emergency rescue skills" and "panning and performing prosthetic treatment."

Characteristics and Trends of Pediatric Trauma in Jeju Island, South Korea: A Community Level Serial Cross-sectional study.

Objective: This study aimed to investigate the characteristics and epidemiological trends of pediatric injuries among patients visiting emergency departments (EDs) on Jeju Island. Method: Employing a community-level serial cross-sectional analysis, we targeted pediatric patients aged 18 years or younger who visited EDs for injuries over a ten-year period. The data, sourced from the Jeju Injury Surveillance System (JISS), facilitated a comprehensive examination of injury characteristics and epidemiological trends. This included an evaluation of the annual incidence and overall trends in pediatric injury cases. Results: The study found toddlers (42.5% of cases) to be the most frequently injured age group. Males were more prone to injuries, with a male-to-female ratio of 1.7:1. Injuries among visitors accounted for 17.3% of cases, with a seasonal spike in Summer, evenings and weekends. Most incidents occurred at home, predominantly accidental in nature, with adolescents more likely to require EMS services. The common mechanisms of injuries were blunt force (49.2%), slips/falls (22.0%), and motor vehicle collisions (13.2%), leading to bruises, cuts, and sprains. Over the decade, a general increase in pediatric injuries was observed. Accidental injuries initially surged but later stabilized, while self-harm/suicide and assault/violence injuries showed a concerning upward trend. Age-specific analysis revealed increasing trends in infants and adolescents. Conclusion: The study underscores the crucial need for targeted injury prevention and resource allocation strategies, particularly for high-risk groups and times, to effectively mitigate pediatric trauma on Jeju Island.

Inhibitory effect of doxycycline conjugated with deoxycholic acid and polyethylenimine conjugate on nasal fibroblast differentiation and extracellular production.

BACKGROUND: Chronic rhinosinusitis (CRS) is an inflammatory disease affecting the sinuses or nose. Persistent inflammatory responses can lead to tissue remodeling, which is a pathological characteristics of CRS. Activation of fibroblasts in the nasal mucosal stroma, differentiation and collagen deposition, and subepithelial fibrosis have been associated with CRS. OBJECTIVES: We aimed to assess the inhibitory effects of doxycycline and deoxycholic acid-polyethyleneimine conjugate (DA3-Doxy) on myofibroblast differentiation and extracellular matrix (ECM) production in nasal fibroblasts stimulated with TGF-ß1. METHODS: To enhance efficacy, we prepared DA3-Doxy using a conjugate of low-molecular-weight polyethyleneimine (PEI) (MW 1800) and deoxycholic acid (DA) and Doxy. The synthesis of the DA3-Doxy polymer was confirmed using nuclear magnetic resonance, and the critical micelle concentration required for cationic micelle formation through self-assembly was determined. Subsequently, the Doxy loading efficiency of DA3 was assessed. The cytotoxicity of Doxy, DA3, PEI, and DA-Doxy in nasal fibroblasts was evaluated using the WST-1 assay. The anti-tissue remodeling and anti-inflammatory effects of DA3-Doxy and DA3 were examined using real-time polymerase chain reaction (Real-time PCR), immunocytochemistry, western blot, and Sircol assay. RESULTS: Both DA3 and DA3-Doxy exhibited cytotoxicity at 10 µg/ml in nasal fibroblasts. Doxy partially inhibited α-smooth muscle actin, collagen types I and III, and fibronectin. However, DA3-Doxy significantly inhibited α-SMA, collagen types I and III, and fibronectin at 5 µg/ml. DA3-Doxy also modulated TGF-ß1-induced changes in the expression of MMP 1, 2, and 9. Nonetheless, TGF-ß1-induced expression of MMP3 was further increased by DA3-Doxy. The expression of TIMP 1 and 2 was partially reduced with 5 µg/ml DA3-Doxy. CONCLUSIONS: Although initially developed for the delivery of genetic materials or drugs, DA3 exhibits inhibitory effects on myofibroblast differentiation and ECM production. Therefore, it holds therapeutic potential for CRS, and a synergistic effect can be expected when loaded with CRS treatment drugs.

Identification of Fibrinogen as a Plasma Protein Binding Partner for Lecanemab Biosimilar IgG: Implications for Alzheimer's Disease Therapy.

OBJECTIVE: Recombinant monoclonal therapeutic antibodies like lecanemab, which target amyloid beta in Alzheimer's disease, offer a promising approach for modifying the disease progression. Due to its relatively short half-life, Lecanemab, administered as a bi-monthly infusion (typically 10mg/kg) has a relatively brief half-life. Interaction with abundant plasma proteins binder in the bloodstream can affect pharmacokinetics of drugs, including their half-life. In this study we investigated potential plasma protein binding interaction to lecanemab using lecanemab biosimilar. METHODS: Lecanemab biosimilar used in this study was based on publicly available sequences. ELISA and Western blotting were used to assess lecanemab biosimilar immunoreactivity in the fractions human plasma sample obtained through size exclusion chromatography. The binding of lecanemab biosimilar to candidate binders was confirmed by Western blotting, ELISA, and surface plasmon resonance analysis. RESULTS: Using a combination of equilibrium dialysis, ELISA, and Western blotting in human plasma, we first describe the presence of likely plasma protein binding partner to lecanemab biosimilar, and then identify fibrinogen as one of them. Utilizing surface plasmon resonance, we confirmed that lecanemab biosimilar does bind to fibrinogen, although with lower affinity than to monomeric amyloid beta. CONCLUSION: In the context of lecanemab therapy, these results imply that fibrinogen levels could impact the levels of free antibodies in the bloodstream and that fibrinogen might serve as a reservoir for lecanemab. More broadly, these results indicate that plasma protein binding may be an important consideration when clinically utilizing therapeutic antibodies in neurodegenerative disease.

Euonymus hamiltonianus Extract Improves Amnesia in APPswe/Tau Transgenic and Scopolamine-Induced Dementia Models.

Dementia is a syndrome exhibiting progressive impairments on cognition and behavior beyond the normal course of aging, and Alzheimer's disease (AD) is one of the neurodegenerative diseases known to cause dementia. We investigated the effect of KGC07EH, the 30% ethanol extract of Euonymus hamiltonianus, against amyloid-ß (Aß) production and cognitive dysfunction in dementia models. KGC07EH was treated on Hela cells expressing the Swedish mutant form of amyloid precursor protein (APP), and the AD triple transgenic (3× TG) mice were given KGC07EH orally during 11-14 months of age (100 and 300 mg/kg/day). SH-SY5Y cell line was used to test KGC07EH on scopolamine-induced elevation of acetylcholinesterase (AChE) activity. ICR mice were intraperitoneally injected with scopolamine, and KGC07EH was administered orally (50, 100, and 200 mg/kg/day) for 4 weeks. KGC07EH treatment decreased Aß, sAPPß-sw, and sAPPß-wt levels and APP protein expressions while sAPPα was increased in Swedish mutant-transfected HeLa cells. KGC07EH treatment also significantly reduced the accumulation of Aß plaques and tau tangles in the brain of 3× TG mice as well as improving the cognitive function. In SH-SY5Y cells cultured with scopolamine, KGC07EH dose-dependently attenuated the increase of AChE activity. KGC07EH also improved scopolamine-induced learning and memory impairment in scopolamine-injected mice, and in their cerebral cortex and hippocampus, the expression levels of p-ERK, p-CREB, p-Akt, and BDNF were attenuated. KGC07EH inhibits APP processing and Aß production both in vitro and in vivo, while enhancing acetylcholine signaling and cognitive dysfunction which are the major symptoms of dementia.

Exploring the Metabolic Effects of a Herbal Remedy of Asarum sieboldii, Platycodon grandiflorum, and Cinnamomum cassia Extracts: Unraveling Its Therapeutic Potential as a Topical Application for Atopic Dermatitis Treatment.

Our previous study demonstrated that our novel herbal remedy, a mixture of Asarum sieboldii, Platycodon grandiflorum, and Cinnamomum Cassia extracts, exhibits a therapeutic effect in 1-chloro-2,4-dinitrobenzene (DNCB)-induced mice by inhibiting the Th-2 inflammatory response upon oral administration. It also ameliorated imbalances in lipid metabolism related to the skin barrier function in keratinocytes, indicating its potential as a topical agent. This study aims to further investigate the therapeutic effects and metabolic mechanisms of its topical application. The anti-atopic effect was evaluated using dermatitis scores, histopathological analysis, and immune cell factors in DNCB-induced mice. Metabolomic profiling of serum and lesional skin was conducted to elucidate the metabolic mechanisms. The topical application significantly reduced dermatitis scores, mast cell infiltration, and serum levels of immunoglobulin E (IgE), IFN-γ, interleukin (IL)-4, IL-17, and thymic stromal lymphopoietin (TSLP), demonstrating its effectiveness in treating atopic dermatitis (AD). Serum metabolomics revealed alterations in fatty acid metabolism related to the pro-inflammatory response. In lesional skin, metabolic markers associated with oxidative stress, immune regulation, and AD symptoms were restored. This study demonstrated its potential as a topical agent in suppressing Th-2 inflammatory responses and improving metabolic abnormalities related to AD symptoms, providing crucial insights for developing natural AD treatments.

Barium molybdate up-conversion nanoscale particles with IR-LED chip, temperature sensing, and anti-counterfeiting applications.

Barium molybdate nanoparticles exhibiting up-conversion luminescence were synthesized via the solvothermal method. Analysis revealed a prominent signal corresponding to the (112) plane in the XRD pattern, indicating the tetragonal structure of the synthesized nanoparticles. Raman spectroscopy detected the symmetric stretching frequencies of MoO4. When excited at 980 nm, the nanoparticles emitted a green spectrum with peaks at 532 and 553 nm. The luminescence intensity varied with the excitation light source, supporting the mechanism involving energy transfer from Yb-doped Er ions via the two-photon effect of the up-conversion phosphor. Moreover, the synthesized nanoparticles exhibited diminished luminous intensity with increasing temperature, suggesting potential for flexible composite sensor fabrication. Integration with a 980 nm LED chip yielded a green emission color. Furthermore, when applied to banknotes, plastic cards, fabrics, and artwork, the opaque solution mixed with polymers remained invisible to the naked eye; however, under 980 nm laser irradiation, the distinct green color became apparent, offering a viable approach for anti-counterfeiting measures.

Stilbenoid derivatives as potent inhibitors of HIF-1α-centric cancer metabolism under hypoxia.

Hypoxia-inducible factor (HIF)-1α is a crucial transcription factor associated with cancer metabolism and is regarded as a potent anticancer therapeutic strategy within the hypoxic microenvironment of cancer. In this study, stilbenoid derivatives were designed, synthesized, and assessed for their capacity to inhibit HIF-1α-associated cancer metabolism and evaluated for inhibition of cancer cell viability and HIF activation. Through the structure-activity relationship studies, compound 28e was identified as the most potent derivative. Specifically, under the hypoxic condition, 28e reduced the accumulation of HIF-1α protein and the expression of its target genes related to glucose metabolism without affecting the expression of HIF-1α mRNA. Furthermore, 28e inhibited glucose uptake, glycolytic metabolism, and mitochondrial respiration, decreasing cellular ATP production under hypoxic conditions. In addition, 28e displayed significant anti-tumor effects and effectively suppressed the accumulation of HIF-1α protein in tumor tissue in vivo xenograft model. These findings suggest that our stilbenoid derivatives exert their anticancer effects by targeting HIF-1α-centered cancer metabolism under hypoxic conditions.

Impacts of Pre-transplant Panel-Reactive Antibody on Post-transplantation Outcomes: A Study of Nationwide Heart Transplant Registry Data.

BACKGROUND AND OBJECTIVES: The number of sensitized heart failure patients on waiting lists for heart transplantation (HTx) is increasing. Using the Korean Organ Transplantation Registry (KOTRY), a nationwide multicenter database, we investigated the prevalence and clinical impact of calculated panel-reactive antibody (cPRA) in patients undergoing HTx. METHODS: We retrospectively reviewed 813 patients who underwent HTx between 2014 and 2021. Patients were grouped according to peak PRA level as group A: patients with cPRA ≤10% (n= 492); group B: patients with cPRA >10%, <50% (n=160); group C patients with cPRA ≥50% (n=161). Post-HTx outcomes were freedom from antibody-mediated rejection (AMR), acute cellular rejection, coronary allograft vasculopathy, and all-cause mortality. RESULTS: The median follow-up duration was 44 (19-72) months. Female sex, re-transplantation, and pre-HTx renal replacement therapy were independently associated with an increased risk of sensitization (cPRA ≥50%). Group C patients were more likely to have longer hospital stays and to use anti-thymocyte globulin as an induction agent compared to groups A and B. Significantly more patients in group C had positive flow cytometric crossmatch and had a higher incidence of preformed donor-specific antibody (DSA) compared to groups A and B. During follow-up, group C had a significantly higher rate of AMR, but the overall survival rate was comparable to that of groups A and B. In a subgroup analysis of group C, post-transplant survival was comparable despite higher preformed DSA in a desensitized group compared to the non-desensitized group. CONCLUSIONS: Patients with cPRA ≥50% had significantly higher incidence of preformed DSA and lower freedom from AMR, but post-HTx survival rates were similar to those with cPRA <50%. Our findings suggest that sensitized patients can attain comparable post-transplant survival to non-sensitized patients when treated with optimal desensitization treatment and therapeutic intervention.

Switching from tenofovir disoproxil fumarate to tenofovir alafenamide in virologically suppressed patient with chronic hepatitis B.

BACKGROUND AND AIM: Our study evaluated the outcomes of switching from tenofovir disoproxil fumarate (TDF) to tenofovir alafenamide (TAF) in patients with chronic hepatitis B (CHB). We assessed viral and biochemical responses as well as changes in the estimated glomerular filtration rate (eGFR) and bone mineral density (BMD). METHODS: This retrospective multicenter study included CHB patients who achieved virologic response (VR) (HBV DNA < 20 IU/mL) while on TDF and were subsequently switched to TAF between April 2018 and October 2021. RESULTS: This study included 309 patients with a median age of 59 years, and 42.1% were male. The mean duration of TDF and TAF administration were 54.0 and 37.5 months, respectively. All patients maintained VR after switching to TAF. Alanine aminotransferase (ALT) normalization rate significantly increased 6 months after switching (74.8%-83.5%; P = 0.008). Adjusted eGFR significantly improved at 6 months (+5.55 ± 10.52 mL/min/1.73 m2; P < 0.001) and 12 months (+6.02 ± 10.70 mL/min/1.73 m2; P < 0.001) after switching. In the subgroup of patients with renal impairment (eGFR < 60 mL/min/1.73 m2), significant improvement in renal function was observed at 6 months (+0.6 ± 10.5 mL/min/1.73 m2; P < 0.001) and 12 months (+1.0 ± 10.7 mL/min/1.73 m2; P < 0.001) after switching to TAF. In patients with osteoporosis (n = 182), switching to TAF resulted in significant improvement in spine and hip BMD at 12 months, with increases of 9.7% (95% CI: 7.0-12.5) and 9.4% (95% CI: 7.0-11.8), respectively. CONCLUSION: In this real-world study, switching to TAF was effective and safe in patients, with notable improvements in ALT levels, renal function, and BMD.

Brain plasticity and ginseng.

Brain plasticity refers to the brain's ability to modify its structure, accompanied by its functional changes. It is influenced by learning, experiences, and dietary factors, even in later life. Accumulated researches have indicated that ginseng may protect the brain and enhance its function in pathological conditions. There is a compelling need for a more comprehensive understanding of ginseng's role in the physiological condition because many individuals without specific diseases seek to improve their health by incorporating ginseng into their routines. This review aims to deepen our understanding of how ginseng affects brain plasticity of people undergoing normal aging process. We provided a summary of studies that reported the impact of ginseng on brain plasticity and related factors in human clinical studies. Furthermore, we explored researches focused on the molecular mechanisms underpinning the influence of ginseng on brain plasticity and factors contributing to brain plasticity. Evidences indicate that ginseng has the potential to enhance brain plasticity in the context of normal aging by mediating both central and peripheral systems, thereby expecting to improve age-related declines in brain function. Moreover, given modern western diet can damage neuroplasticity in the long term, ginseng can be a beneficial supplement for better brain health.

VA-ECMO weaning strategy using adjusted pulse pressure by vasoactive inotropic score in AMI complicated by cardiogenic shock.

AIMS: This study evaluated how well serial pulse pressure (PP) and PP adjusted by the vasoactive inotropic score (VIS) predicted venoarterial extracorporeal membrane oxygenation (VA-ECMO) weaning success and clinical outcomes in acute myocardial infarction complicated by cardiogenic shock (AMI-CS) patients. METHODS AND RESULTS: A total of 213 patients with AMI-CS who received VA-ECMO between January 2010 and August 2021 were enrolled in the institutional ECMO registry. Serial PP and VIS were measured immediately, 12, 24, and 48 h after VA-ECMO insertion. PP adjusted by VIS was defined as PP/√VIS. The primary outcome was successful VA-ECMO weaning. Successful weaning from VA-ECMO was observed in 151 patients (70.9%). Immediately after VA-ECMO insertion, PP [successful vs. failed weaning, 26.0 (15.5-46.0) vs. 21.0 (12.5-33.0), P = 0.386] and PP/√VIS [11.1 (5.1-25.0) vs. 6.0 (3.1-14.2), P = 0.118] did not differ between the successful and failed weaning groups. Serial PP and PP adjusted by VIS at 12, 24, and 48 h after VA-ECMO insertion were significantly higher in patients with successful weaning than those with failed weaning [successful vs. failed weaning, 24.0 (4.0-38.0) vs. 12.5 (6.0-25.5), P = 0.007 for 12 h PP, and 10.1 (5.7-22.0) vs. 2.9 (1.7-5.9), P < 0.001 for 12 h PP/√VIS]. The 12 h PP/√VIS showed better discriminative function for successful weaning than 12 h PP alone [area under the curve (AUC) 0.80, 95% confidence interval (CI) 0.72-0.88, P < 0.001 vs. AUC 0.67, 95% CI 0.57-0.77, P = 0.002]. Patients with a low 12 h PP/√VIS (≤7) had higher rates of in-hospital mortality (44.4% vs. 19.8%, P < 0.001) and 6 month follow-up mortality (hazard ratio 2.41, 95% CI 1.49-3.90, P < 0.001) than those with a high 12 h PP/√VIS (>7). CONCLUSIONS: PP adjusted by VIS taken 12 h following VA-ECMO initiation can predict weaning from VA-ECMO more successfully than PP alone, and its low value was associated with a higher risk of mortality in AMI-CS patients.

Overt disseminated intravascular coagulation and antithrombin III predict bleeding and in-hospital mortality in patients undergoing extracorporeal membrane oxygenation.

Background: Limited data are available on the relationship of disseminated intravascular coagulation (DIC) with mortality in patients receiving extracorporeal membrane oxygenation (ECMO). Thus, we investigated the association of DIC score and antithrombin (AT) III with clinical outcomes in patients undergoing ECMO. Methods: We analyzed 703 patients who underwent ECMO between January 2014 and May 2022 at Samsung Medical Center. The DIC score was calculated using laboratory findings within 24 h of the ECMO initiation, and ≥ 5 was defined as overt DIC. In addition, the AT III level was measured to identify the correlation with the DIC score. Results: Among the study patients, 169 (24.0%) were diagnosed with overt DIC (DIC group) during early maintenance therapy. In-hospital mortality was significantly higher in the DIC group than in the non-DIC group (55.0% vs. 36.5%, p < 0.001). Bleeding events were significantly higher in the group of patients with a DIC score of 7 or 8 than in the other group (20.8% vs. 8.4%, p = 0.038). DIC score negatively correlated with AT III level (r = -0.417, p < 0.001). The predictive performance of AT III for overt DIC had statistical significance with a c-static of 0.81 (95% confidence interval (CI), 0.77-0.84, p < 0.001). Conclusion: Overt DIC was associated with higher in-hospital mortality and a tendency to bleed in ECMO patients. Furthermore, AT III plasma levels can easily predict overt DIC in patients undergoing ECMO. These findings suggest that monitoring AT III plasma levels may be important in the management of ECMO.

Neuroimaging and epigenetic analysis reveal novel epigenetic loci in major depressive disorder.

BACKGROUND: Epigenetic modifications, such as DNA methylation, contribute to the pathophysiology of major depressive disorder (MDD). This study aimed to identify novel MDD-associated epigenetic loci using DNA methylation profiles and explore the correlations between epigenetic loci and cortical thickness changes in patients with MDD. METHODS: A total of 350 patients with MDD and 161 healthy controls (HCs) were included in the epigenome-wide association studies (EWAS). We analyzed methylation, copy number alteration (CNA), and gene network profiles in the MDD group. A total of 234 patients with MDD and 135 HCs were included in neuroimaging methylation analysis. Pearson's partial correlation analysis was used to estimate the correlation between cortical thickness of brain regions and DNA methylation levels of the loci. RESULTS: In total, 2018 differentially methylated probes (DMPs) and 351 differentially methylated regions (DMRs) were identified. DMP-related genes were enriched in two networks involved in the central nervous system. In neuroimaging analysis, patients with MDD showed cortical thinning in the prefrontal regions and cortical thickening in several occipital regions. Cortical thickness of the left ventrolateral prefrontal cortex (VLPFC, i.e. pars triangularis) was negatively correlated with eight DMPs associated with six genes (EML6, ZFP64, CLSTN3, KCNMA1, TAOK2, and NT5E). CONCLUSION: Through combining DNA methylation and neuroimaging analyses, negative correlations were identified between the cortical thickness of the left VLPFC and DNA methylation levels of eight DMPs. Our findings could improve our understanding of the pathophysiology of MDD.