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.

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.

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.

A Machine Learning Algorithm Facilitates Prognosis Prediction and Treatment Selection for Barcelona Clinic Liver Cancer Stage C Hepatocellular Carcinoma.

BACKGROUND: Given its heterogeneity and diverse clinical outcomes, precise subclassification of BCLC-C hepatocellular carcinoma (HCC) is required for appropriately determining patient prognosis and selecting treatment. METHODS: We recruited 2,626 patients with BCLC-C stage HCC from multiple centers, comprising training/test (n=1,693) and validation cohorts (n=933). The XGBoost was chosen for maximum performance among the machine learning (ML) models. Patients were categorized into low-/intermediate-/high-/very high-risk subgroups which were based on the estimated prognosis, and this subclassification was named the CLAssification via Machine learning of BCLC-C (CLAM-C). RESULTS: The areas under the receiver operating characteristic curve of the CLAM-C for predicting the 6-/12-/24-month survival of patients with BCLC-C were 0.800/0.831/0.715, respectively-significantly higher than those of the conventional models, which was consistent in the validation cohort. The four subgroups had significantly different median overall survivals, and this difference was maintained among various patient subgroups and treatment modalities. Immune-checkpoint inhibitors and transarterial therapies were associated with significantly better survival than tyrosine kinase inhibitors (TKIs) in the low- and intermediate-risk subgroups. In cases with first-line systemic therapy, the CLAM-C identified atezolizumab-bevacizumab as the best therapy particularly in the high-risk group. In cases with later-line systemic therapy, nivolumab had better survival than TKIs in the low-to-intermediate-risk subgroup, whereas TKIs had better survival in the high-to-very high-risk subgroup. CONCLUSIONS: ML modeling effectively subclassified patients with BCLC-C HCC, potentially aiding treatment allocation. Our study underscores the potential utilization of ML modeling in terms of prognostication and treatment allocation in patients with BCLC-C HCC.

Effects of L-Type Voltage-Gated Calcium Channel (LTCC) Inhibition on Hippocampal Neuronal Death after Pilocarpine-Induced Seizure.

Epilepsy, marked by abnormal and excessive brain neuronal activity, is linked to the activation of L-type voltage-gated calcium channels (LTCCs) in neuronal membranes. LTCCs facilitate the entry of calcium (Ca2+) and other metal ions, such as zinc (Zn2+) and magnesium (Mg2+), into the cytosol. This Ca2+ influx at the presynaptic terminal triggers the release of Zn2+ and glutamate to the postsynaptic terminal. Zn2+ is then transported to the postsynaptic neuron via LTCCs. The resulting Zn2+ accumulation in neurons significantly increases the expression of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subunits, contributing to reactive oxygen species (ROS) generation and neuronal death. Amlodipine (AML), typically used for hypertension and coronary artery disease, works by inhibiting LTCCs. We explored whether AML could mitigate Zn2+ translocation and accumulation in neurons, potentially offering protection against seizure-induced hippocampal neuronal death. We tested this by establishing a rat epilepsy model with pilocarpine and administering AML (10 mg/kg, orally, daily for 7 days) post-epilepsy onset. We assessed cognitive function through behavioral tests and conducted histological analyses for Zn2+ accumulation, oxidative stress, and neuronal death. Our findings show that AML's LTCC inhibition decreased excessive Zn2+ accumulation, reactive oxygen species (ROS) production, and hippocampal neuronal death following seizures. These results suggest amlodipine's potential as a therapeutic agent in seizure management and mitigating seizures' detrimental effects.

Neuroprotective Effects of Chemical Constituents of Leaves of Euonymus hamiltonianus Wall.

Euonymus hamiltonianus Wall. is considered a medicinal plant and is used to treat pain, cough, dysuria, and cancer, but a clear phytochemical investigation of its biological activities has yet to be performed. Investigation of chemical constituents of the leaves of Euonymus hamiltonianus Wall. led to the isolation of three new compounds by chromatography techniques, euonymusins A-C (1, 10, and 11), and the acquisition of new spectroscopic data for euonymusin D (2), along with the identification of ten known compounds. The chemical structures of the compounds were established using extensive spectroscopic techniques, including NMR, MS, and hydrolysis, and compared with the published data. These compounds were tested in vitro for their inhibitory effects on beta amyloid production (Aß42). Compounds 13 and 14 displayed weak inhibition, with IC50 values ranging from 53.15 to 65.43 µM. Moreover, these compounds were also assessed for their inhibitory effects on nitric oxide production. Of these compounds, 3, 4, and 14 displayed inhibitory effects on NO production, with IC50 values ranging from 14.38 to 17.44 µM. Compounds 3, 4, and 14 also suppressed LPS-induced expression of nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) protein.

Outcomes of Concomitant Maze Procedure in Tricuspid Repair for Severe Tricuspid Regurgitation.

BACKGROUND: We aimed to analyze the impact of concomitant Maze procedure on the clinical and rhythm outcomes, and echocardiographic parameters in tricuspid repair for patients with severe tricuspid regurgitation (TR) and persistent atrial fibrillation (AF). METHODS: Patients who had severe TR and persistent AF and underwent tricuspid valve (TV) repair were included in the study. Both primary TR and secondary TR were included in the current study. The study population was stratified according to Maze procedure. The primary outcome was major adverse cardiovascular and cerebrovascular event (MACCE) at 15 years post-surgery. Propensity-score matching analyses was performed to adjust baseline differences. RESULTS: Three hundred seventy-one patients who underwent tricuspid repair for severe TR and persistent AF from 1994 to 2021 were included, and 198 patients (53.4%) underwent concomitant Maze procedure. The maze group showed 10-year sinus rhythm (SR) restoration rate of 55%. In the matched cohort, the maze group showed a lower cumulative incidence of cardiac death (4.6% vs. 14.4%, P = 0.131), readmission for heart failure (8.1% vs. 22.2%, P = 0.073), and MACCE (21.1% vs. 42.1%, P = 0.029) at 15 years compared to the non-maze group. Left atrial (LA) diameter significantly decreased in the maze group at 5 years (53.3 vs. 59.6 mm, P < 0.001) after surgery compared to preoperative level, and there was a significant difference in the change of LA diameter over time between the two groups (P = 0.013). CONCLUSION: The Maze procedure during TV repair in patients with severe TR and persistent AF showed acceptable SR rates and lower MACCE rates compared to those without the procedure, while also promoting LA reverse remodeling.

A phosphodiesterase 4 (PDE4) inhibitor, amlexanox, reduces neuroinflammation and neuronal death after pilocarpine-induced seizure.

Epilepsy, a complex neurological disorder, is characterized by recurrent seizures caused by aberrant electrical activity in the brain. Central to this study is the role of lysosomal dysfunction in epilepsy, which can lead to the accumulation of toxic substrates and impaired autophagy in neurons. Our focus is on phosphodiesterase-4 (PDE4), an enzyme that plays a crucial role in regulating intracellular cyclic adenosine monophosphate (cAMP) levels by converting it into adenosine monophosphate (AMP). In pathological states, including epilepsy, increased PDE4 activity contributes to a decrease in cAMP levels, which may exacerbate neuroinflammatory responses. We hypothesized that amlexanox, an anti-inflammatory drug and non-selective PDE4 inhibitor, could offer neuroprotection by addressing lysosomal dysfunction and mitigating neuroinflammation, ultimately preventing neuronal death in epileptic conditions. Our research utilized a pilocarpine-induced epilepsy animal model to investigate amlexanox's potential benefits. Administered intraperitoneally at a dose of 100 â€‹mg/kg daily following the onset of a seizure, we monitored its effects on lysosomal function, inflammation, neuronal death, and cognitive performance in the brain. Tissue samples from various brain regions were collected at predetermined intervals for a comprehensive analysis. The study's results were significant. Amlexanox effectively improved lysosomal function, which we attribute to the modulation of zinc's influx into the lysosomes, subsequently enhancing autophagic processes and decreasing the release of inflammatory factors. Notably, this led to the attenuation of neuronal death in the hippocampal region. Additionally, cognitive function, assessed through the modified neurological severity score (mNSS) and the Barnes maze test, showed substantial improvements after treatment with amlexanox. These promising outcomes indicate that amlexanox has potential as a therapeutic agent in the treatment of epilepsy and related brain disorders. Its ability to combat lysosomal dysfunction and neuroinflammation positions it as a potential neuroprotective intervention. While these findings are encouraging, further research and clinical trials are essential to fully explore and validate the therapeutic efficacy of amlexanox in epilepsy management.

Lignin-derived carbon quantum dot/PVA films for totally blocking UV and high-energy blue light.

Excessive exposure to UV and high-energy blue light (HEBL) can cause fatal eye and skin injuries. As a result, it is crucial to protect our bodies from UV and HEBL radiation. To achieve complete blocking of UV and HEBL, we developed a lignin-derived carbon quantum dot (L-CQD)/polyvinyl alcohol (PVA) film. L-CQD was synthesized from lignin, a waste woody biomass, and then blended with a PVA matrix to create a flexible L-CQD/PVA film. Thanks to simultaneous UV and HEBL absorption characteristics and bright color of L-CQD, the PVA film with 0.375 wt% L-CQD demonstrated outstanding blocking efficiency: 100 % in UV-C, UV-B, and UV-A, and at least 99.9 % in HEBL. It also exhibited a 44 % increase in lightness and a 12 % enhancement in transparency compared to lignin/PVA film. The film's ability to block UV and HEBL was further demonstrated by reducing >40 % UV-induced ROS formation in both cancerous and normal cell lines (Hs 294T, HeLa, CCD-986sk, and L929), as well as by blocking blue laser diode (LD) and LED. Since the L-CQD/PVA film is simple to produce, environmentally friendly, flexible, and thermally stable, it is suitable for use as a protective coating against sunlight and harmful emissions from IT devices.

Differential liver function at cessation of atezolizumab-bevacizumab versus lenvatinib in HCC: a multicenter, propensity-score matched comparative study.

Background: Atezolizumab+bevacizumab (AB) and lenvatinib have been proposed as first-line treatment options for patients with advanced hepatocellular carcinoma (HCC), but comparative efficacy and associated factors are controversial. Materials and methods: This real-world multicenter study analysed patients with HCC who received AB (n=169) or lenvatinib (n=177). Results: First, 1:1 propensity score matching (PSM) was performed, resulting in 141 patients in both the AB and lenvatinib groups. After PSM, overall survival (OS) was better in the AB group than in the lenvatinib group [hazard ratio (HR)=0.642, P=0.009], but progression-free survival (PFS) did not vary between the two groups (HR=0.817, P=0.132). Objective response rate (ORR) was also similar between AB and lenvatinib (34.8% vs. 30.8%, P=0.581). In a subgroup of patients with objective responses (OR, n=78), OS (HR=0.364, P=0.012) and PFS (HR=0.536, P=0.019) were better in the AB group (n=41) than in the lenvatinib group (n=37). Time-to-progression from time of OR was also better in the AB group (HR=0.465, P=0.012). Importantly, residual liver function was a significant factor related to OS in both treatments. Child-Pugh score following cessation of the respective treatments was better in the AB group (n=105) than in the lenvatinib group (n=126) (median 6 versus 7, P=0.008), and proportion of salvage treatment was also higher in the AB group (52.4% versus 38.9%, P=0.047). When we adjusted for residual liver function or salvage treatment, there was no difference in OS between the two treatments. Conclusion: Our study suggests that residual liver function and subsequent salvage treatments are major determinants of clinical outcomes in patients treated with AB and lenvatinib; these factors should be considered in future comparative studies.

Plasma VEGFA and PGF impact longitudinal tau and cognition in preclinical Alzheimer's disease.

Vascular dysfunction is increasingly recognized as an important contributor to the pathogenesis of Alzheimer's disease. Alterations in vascular endothelial growth factor (VEGF) pathways have been implicated as potential mechanisms. However, the specific impact of VEGF proteins in preclinical Alzheimer's disease and their relationships with other Alzheimer's disease and vascular pathologies during this critical early period remain to be elucidated. We included 317 older adults from the Harvard Aging Brain Study, a cohort of individuals who were cognitively unimpaired at baseline and followed longitudinally for up to 12 years. Baseline VEGF family protein levels (VEGFA, VEGFC, VEGFD, PGF and FLT1) were measured in fasting plasma using high-sensitivity immunoassays. Using linear mixed effects models, we examined the interactive effects of baseline plasma VEGF proteins and amyloid PET burden (Pittsburgh Compound-B) on longitudinal cognition (Preclinical Alzheimer Cognitive Composite-5). We further investigated if effects on cognition were mediated by early neocortical tau accumulation (flortaucipir PET burden in the inferior temporal cortex) or hippocampal atrophy. Lastly, we examined the impact of adjusting for baseline cardiovascular risk score or white matter hyperintensity volume. Baseline plasma VEGFA and PGF each showed a significant interaction with amyloid burden on prospective cognitive decline. Specifically, low VEGFA and high PGF were associated with greater cognitive decline in individuals with elevated amyloid, i.e. those on the Alzheimer's disease continuum. Concordantly, low VEGFA and high PGF were associated with accelerated longitudinal tau accumulation in those with elevated amyloid. Moderated mediation analyses confirmed that accelerated tau accumulation fully mediated the effects of low VEGFA and partially mediated (31%) the effects of high PGF on faster amyloid-related cognitive decline. The effects of VEGFA and PGF on tau and cognition remained significant after adjusting for cardiovascular risk score or white matter hyperintensity volume. There were concordant but non-significant associations with longitudinal hippocampal atrophy. Together, our findings implicate low VEGFA and high PGF in accelerating early neocortical tau pathology and cognitive decline in preclinical Alzheimer's disease. Additionally, our results underscore the potential of these minimally-invasive plasma biomarkers to inform the risk of Alzheimer's disease progression in the preclinical population. Importantly, VEGFA and PGF appear to capture distinct effects from vascular risks and cerebrovascular injury. This highlights their potential as new therapeutic targets, in combination with anti-amyloid and traditional vascular risk reduction therapies, to slow the trajectory of preclinical Alzheimer's disease and delay or prevent the onset of cognitive decline.

Surgical Correction of Left Ventricular Assist Device Outflow Graft Obstruction Caused by a Wrapped Expanded Polytetrafluoroethylene Graft: A Case Report.

A 70-year-old man with dilated cardiomyopathy underwent left ventricular assist device (LVAD) implantation, using a HeartWare ventricular assist device, as a bridge to candidacy. After 26 months, computed tomography (CT) angiography indicated stenosis in the LVAD outflow graft; however, the patient was asymptomatic, prompting a decision to manage his condition with close monitoring. Ten months later, the patient presented with dizziness and low-flow alerts. Subsequent CT angiography revealed a critical obstruction involving the entire LVAD outflow graft. The patient underwent emergency surgery, during which an organized seroma causing the graft obstruction was found between a wrapped expanded polytetrafluoroethylene (ePTFE) graft and a Dacron outflow graft. The covering of the outflow graft was removed, along with the organized seroma. Following removal of the ePTFE wrap and decompression of the outflow graft, normal LVAD flow was reestablished. The practice of wrapping the outflow graft with synthetic material, commonly done to facilitate later redo sternotomy, may pose a risk for outflow graft obstruction.

Identification of signature gene set as highly accurate determination of metabolic dysfunction-associated steatotic liver disease progression.

BACKGROUND/AIMS: Metabolic dysfunction-associated steatotic liver disease (MASLD) is characterized by fat accumulation in the liver. MASLD encompasses both steatosis and MASH. Since MASH can lead to cirrhosis and liver cancer, steatosis and MASH must be distinguished during patient treatment. Here, we investigate the genomes, epigenomes, and transcriptomes of MASLD patients to identify signature gene set for more accurate tracking of MASLD progression. METHODS: Biopsy-tissue and blood samples from patients with 134 MASLD, comprising 60 steatosis and 74 MASH patients were performed omics analysis. SVM learning algorithm were used to calculate most predictive features. Linear regression was applied to find signature gene set that distinguish the stage of MASLD and to validate their application into independent cohort of MASLD. RESULTS: After performing WGS, WES, WGBS, and total RNA-seq on 134 biopsy samples from confirmed MASLD patients, we provided 1,955 MASLD-associated features, out of 3,176 somatic variant callings, 58 DMRs, and 1,393 DEGs that track MASLD progression. Then, we used a SVM learning algorithm to analyze the data and select the most predictive features. Using linear regression, we identified a signature gene set capable of differentiating the various stages of MASLD and verified it in different independent cohorts of MASLD and a liver cancer cohort. CONCLUSION: We identified a signature gene set (i.e., CAPG, HYAL3, WIPI1, TREM2, SPP1, and RNASE6) with strong potential as a panel of diagnostic genes of MASLD-associated disease.

Long-term results of atrial fibrillation surgery concomitant with mitral valve surgery: A propensity score-matched multicenter study.

OBJECTIVE: The aim of the study was to elucidate the long-term outcomes of atrial fibrillation surgery in patients with atrial fibrillation and mitral valve disease by comparing the patients who underwent mitral valve surgery with and without atrial fibrillation surgery. METHODS: Between 2005 and 2017, 2680 patients with atrial fibrillation who underwent mitral valve surgery (mitral valve surgery with atrial fibrillation surgery, n = 1841; mitral valve surgery without atrial fibrillation surgery, n = 839) at 5 centers were included. After propensity score matching, 1442 patients were extracted (atrial fibrillation surgery group, n = 721; non-atrial fibrillation surgery group, n = 721). All-cause mortality, cardiac mortality, major adverse cardiac and cerebrovascular events, stroke or transient ischemic attack, and permanent pacemaker implantation were compared between the atrial fibrillation surgery and non-atrial fibrillation surgery groups. RESULTS: Overall survivals at 5 and 10 years postoperatively were 91.0% and 80.7% in the atrial fibrillation surgery group and 86.5% and 75.9% in the non-atrial fibrillation surgery group, respectively (P = .013). Cardiac mortality-free survivals at 5 and 10 years postoperatively were 96.9% and 91.7% in the atrial fibrillation surgery group and 90.9% and 83.7% in the non-atrial fibrillation surgery group, respectively (P < .001). Cumulative incidence of reoperation, major adverse cardiac and cerebrovascular events, and stroke or transient ischemic attack was lower in the matched atrial fibrillation surgery group compared with the matched non-atrial fibrillation surgery group up to 15 years postoperatively (P = .010, P < .001, and P = .012, respectively). Cumulative incidence of permanent pacemaker implantation was higher in the matched atrial fibrillation surgery group compared with the matched non-atrial fibrillation surgery group (P < .001). CONCLUSIONS: In patients with atrial fibrillation and mitral valve disease, mitral valve surgery concomitant with atrial fibrillation surgery was associated with lower mortality, cardiac mortality, major adverse cardiac and cerebrovascular events, and stroke or transient ischemic attack up to 15 years after surgery when compared with mitral valve surgery without atrial fibrillation surgery.

Unexpected Restart Failure of Durable Left Ventricular Assist Devices: A Report of Two Cases.

The HeartWare Ventricular Assist Device (HVAD) was widely used for mechanical circulatory support in patients with end-stage heart failure. However, there have been reports of a critical issue with HVAD pumps failing to restart, or experiencing delays in restarting, after being stopped. This case report describes 2 instances of HVAD failure-to-restart during heart transplantation surgery and routine outpatient care. Despite multiple attempts to restart the pump using various controllers and extensions, the HVAD failed to restart, triggering a hazard alarm for pump stoppage. In one case, the patient survived after receiving a heart transplantation, while in the other, the patient died immediately following the controller exchange. These cases highlight the rare but life-threatening complication of HVAD failure-to-restart, underscoring the importance of awareness among clinicians, patients, and caregivers, and adherence to the manufacturer's guidelines and recommendations for HVAD management.

Pericardial Window Operation in Oncology Patients: Analysis of Long-Term Survival and Prognostic Factors.

Background: Pericardial effusion (PE) is a serious condition in cancer patients, primarily arising from malignant dissemination. Pericardial window formation is a surgical intervention for refractory PE. However, the long-term outcomes and factors associated with postoperative survival remain unclear. Methods: We retrospectively analyzed data from 166 oncology patients who underwent pericardial window formation at Samsung Medical Center between 2011 and 2023. We analyzed survival and PE recurrence regarding surgical approach, cancer type, and cytopathological findings. To identify factors associated with survival, we utilized Cox proportional-hazards regression. Results: All patients had tumors documented in accordance with the American Joint Committee on Cancer staging manual, including lung (61.4%), breast (9.6%), gastrointestinal (9.0%), hematologic (3.6%), and other cancers (16.4%). Surgical approaches included mini-thoracotomy (67.5%) and thoracoscopy (32.5%). Postsurgical cytopathology confirmed malignancy in 94 cases (56.6%). Over a median follow-up duration of 50.0 months, 142 deaths and 16 PE recurrences occurred. The 1-year overall and PE recurrence-free survival rates were 31.4% and 28.6%, respectively. One-year survival rates were significantly higher for thoracoscopy recipients (43.7% vs. 25.6%, p=0.031) and patients with negative cytopathology results (45.1% vs. 20.6%, p<0.001). No significant survival difference was observed between lung cancer and other types (p=0.129). Multivariate analysis identified New York Heart Association class, cancer stage, and cytopathology as independent prognostic factors. Conclusion: This series is the largest to date concerning window formation among cancer patients with PE. Patients' long-term survival after surgery was generally unfavorable. However, cases with negative cytopathology or earlier tumor stage demonstrated comparatively high survival rates.

Development of a tetrahydroindazolone-based HDAC6 inhibitor with in-vivo anti-arthritic activity.

Histone deacetylase 6 (HDAC6) induces the expression of pro-inflammatory cytokines in macrophages; therefore, HDAC inhibitors may be beneficial for the treatment of macrophage-associated immune disorders and chronic inflammatory diseases, including atherosclerosis and rheumatoid arthritis. Structure-activity relationship studies were conducted on various phenyl hydroxamate HDAC6 inhibitors with indolone/indazolone-based bi- or tricyclic ring moieties as the cap group aiming to develop novel anti-arthritic drug candidates. Several compounds exhibited nanomolar activity and HDAC6 selectivity greater than 500-fold over HDAC1. Compound 21, a derivative with the tetrahydroindazolone cap group, is a potent HDAC6 inhibitor with an IC50 of 18 nM and 217-fold selectivity over HDAC1 and showed favorable oral bioavailability in animals. Compound 21 increases the acetylation level of tubulin without affecting histone acetylation in cutaneous T-cell lymphoma cells and inhibits TNF-α secretion in LPS-stimulated macrophage cells. The anti-arthritic effects of compound 21 were evaluated using a rat adjuvant-induced arthritis (AIA) model. Treatment with compound 21 significantly reduced the arthritis score, and combination treatment with methotrexate showed a synergistic effect in AIA models. We identified a novel HDAC6 inhibitor, compound 21, with excellent in vivo anti-arthritic efficacy, which can lead to the development of oral anti-arthritic drugs.

Risk Stratification of Pancreatic Ductal Adenocarcinoma Patients Undergoing Curative-Intent Surgery after Neoadjuvant Therapy.

PURPOSE: Clinical prognostic criteria using preoperative factors were not developed for post-neoadjuvant therapy (NAT) surgery of pancreatic ductal adenocarcinoma (PDAC). We aimed to identify preoperative factors associated with overall survival (OS) in PDAC patients who underwent post-NAT curative-intent surgery and develop risk stratification criteria. MATERIALS AND METHODS: Consecutive PDAC patients who underwent post-NAT curative-intent surgeries between 2007 and 2020 were retrospectively analyzed. Demographic, laboratory, surgical, and histopathologic variables were collected. Baseline, preoperative, and interval changes of computed tomography (CT) findings proposed by the Society of Abdominal Radiology and the American Pancreatic Association were analyzed. Cox proportional hazard analysis was used to select preoperative variables associated with OS. We developed risk stratification criteria composed of the significant preoperative variables, i.e., post-NAT response criteria. We compared the discrimination performance of post-NAT response criteria with that of post-NAT pathological (yp) American Joint Cancer Committee TNM staging system. RESULTS: One hundred forty-five PDAC patients were included. Stable or increased tumor size on CT (hazard ratio [HR], 2.58; 95% confidence interval [CI], 1.58 to 4.21; p < 0.001) and elevated preoperative carbohydrate antigen 19-9 (CA19-9) level (HR, 1.98; 95% CI, 1.11 to 3.55; p=0.021) were independent factors of OS. The OS of the patient groups stratified by post-NAT response criteria which combined changes in tumor size and CA19-9 showed significant difference (p < 0.001). Such stratification was comparable to ypTNM staging in discrimination performance (difference of C-index, 0.068; 95% CI, -0.012 to 0.142). CONCLUSION: "Any degree of decrease in tumor size on CT" and CA19-9 normalization or staying normal were independent favorable factors of OS. The combination of the two factors discriminated OS comparably to ypTNM staging.

Anesthetic management for non-cardiac surgery in patients with left ventricular assist devices.

With the growing number of patients undergoing left ventricular assist device (LVAD) implantation and improved survival in this population, more patients with LVADs are presenting for various types of non-cardiac surgery. Therefore, anesthesiologists need to understand the physiology and adequately prepare for the perioperative management of this unique patient population. This review addresses perioperative considerations and intraoperative management for the safe and successful management of patients with an LVAD undergoing non-cardiac surgery. Understanding the basic physiology of preload dependency and afterload sensitivity in these patients is essential. The main considerations include a collaborative preoperative multidisciplinary approach, perioperative care aimed at optimizing the intravascular volume and right ventricular function, and maintaining the afterload within recommended ranges for optimal LVAD function.