Endovascular Stenting as a First Choice for the Palliation of Superior Vena Cava Syndrome

To assess the effectiveness of endovascular stenting for the palliation of superior vena cava (SVC) syndrome, endovascular stent insertion was attempted in 10 patients with symptomatic occlusion of the SVC. All the patients had known malignant disease of the thorax. Eight patients had been treated previously with chemotherapy and radiotherapy (n=5), chemotherapy alone (n=2), or pneumonectomy and radiotherapy (n=1). After developing SVC syndrome, all the patients were stented before receiving any other treatment. After single or multiple endovascular stents were inserted, five of eight patients were treated with chemotherapy and radiotherapy (n=2) or chemotherapy alone (n=3). Resolution of symptoms was achieved in nine patients within 72 hr (90%). In one patient, the symptoms did not disappear until a second intervention. At follow up, symptoms had recurred in two of ten patients (20%) after intervals of 15 and 60 days. Five patients have died from their cancers, although they remained free of symptoms of SVC occlusion until death. In conclusion, endovascular stent insertion is an effective treatment for palliation of SVC syndrome. Endovascular stent insertion can be considered the first choice of treatment, due to the immediate relief of symptoms and excellent sustained symptomatic relief

Adjuvant radiotherapy versus observation following gross total resection for atypical meningioma: a systematic review and meta-analysis

Background The impact of adjuvant radiotherapy (RT) on atypical meningioma (AM) underwent a gross total resection (GTR) remains unclear, showing conflicting results from various studies. The objective of this study was to perform an updated meta-analysis for observational studies to determine the effect of adjuvant RT after GTR on local recurrence and survival outcomes compared to observation after GTR. Methods PubMed, Embase, and Web of Science were searched to identify comparative studies that reported outcomes of adjuvant RT versus observation for AM patients after GTR. Local recurrence rate, progression-free survival (PFS), overall survival (OS), and toxicities related to RT were considered as outcomes of interest. Differences between two cohorts were estimated by calculating odds ratios (OR) for LR rate and hazard ratios (HR) for survival outcomes with 95% confidence intervals (CIs) for meta-analysis, using R version 4.0.3 software. Included studies were appraised with the Risk of Bias Assessment tool for Non-Randomized Studies. Outcome ratios were combined with the Mantel–Haenszel method and the inverse variance-weighted method, appropriately. Results Data from 30 studies involving 2904 patients (adjuvant RT: n = 737; observation: n = 2167) were eventually included. Significant reduction of local recurrence rate was seen in the adjuvant RT cohort compare to that in the observation cohort (OR 0.50; 95% CI 0.36–0.68; p  5-year revealed that adjuvant RT was superior to observation. There was no significant difference in OS between the two cohorts during any period. Most toxicities were tolerable with grade 1 or 2. There was no documented grade 5 toxicity. Conclusions For AM patients who underwent GTR, evidence suggested that adjuvant RT could potentially decrease local recurrence and improve PFS better than observation

OGLE-2016-BLG-1227L: A Wide-separation Planet from a Very Short-timescale Microlensing Event

We present the analysis of the microlensing event OGLE-2016-BLG-1227. The light curve of this short-duration event appears to be a single-lens event affected by severe finite-source effects. Analysis of the light curve based on single-lens single-source (1L1S) modeling yields very small values of the event timescale, t_E ∼ 3.5 days, and the angular Einstein radius, θ_E ∼ 0.009 mas, making the lens a candidate of a free-floating planet. Close inspection reveals that the 1L1S solution leaves small residuals with amplitude ΔI ≲ 0.03 mag. We find that the residuals are explained by the existence of an additional widely-separated heavier lens component, indicating that the lens is a wide-separation planetary system rather than a free-floating planet. From Bayesian analysis, it is estimated that the planet has a mass of _p = 0.79^(+1.30)_(−0.39) M_J and it is orbiting a low-mass host star with a mass of M_(host) = 0.10+0.17−0.05 M_⊙ located with a projected separation of a_ = 3.4^(+2.1)_(−1.0) au. The planetary system is located in the Galactic bulge with a line-of-sight separation from the source star of D_(LS) = 1.21^(+0.96)_(−0.63) kpc. The event shows that there are a range of deviations in the signatures of host stars for apparently isolated planetary lensing events and that it is possible to identify a host even when a deviation is subtle

Ginseng Berry Extract Prevents Atherogenesis via Anti-Inflammatory Action by Upregulating Phase II Gene Expression

Ginseng berry possesses higher ginsenoside content than its root, which has been traditionally used in herbal medicine for many human diseases, including atherosclerosis. We here examined the antiatherogenic effects of the Korean ginseng berry extract (KGBE) and investigated its underlying mechanism of action in vitro and in vivo. Administration of KGBE decreased atherosclerotic lesions, which was inversely correlated with the expression levels of phase II genes to include heme oxygenase-1 (HO-1) and glutamine-cysteine ligase (GCL). Furthermore, KGBE administration suppressed NF-κB-mediated expression of atherogenic inflammatory genes (TNF-α, IL-1β, iNOS, COX-2, ICAM-1, and VCAM-1), without altering serum cholesterol levels, in ApoE-/- mice fed a high fat-diet. Treatment with KGBE increased phase II gene expression and suppressed lipopolysaccharide-induced reactive oxygen species production, NF-κB activation, and inflammatory gene expression in primary macrophages. Importantly, these cellular events were blocked by selective inhibitors of HO-1 and GCL. In addition, these inhibitors reversed the suppressive effect of KGBE on TNF-α-mediated induction of ICAM-1 and VCAM-1, resulting in decreased interaction between endothelial cells and monocytes. These results suggest that KGBE ameliorates atherosclerosis by inhibiting NF-κB-mediated expression of atherogenic genes via upregulation of phase II enzymes and thus has therapeutic or preventive potential for atherosclerosis

Hemo-metabolic impairment in patients with ST-segment elevation myocardial infarction: Data from the INTERSTELLAR registry

Background: Not only hemo-dynamic (HD) factors but also hemo-metabolic (HM) risk factors reflecting multi-organ injuries are considered as important prognostic factors in ST-segment elevation myocardial infarction (STEMI). However, studies regarding HM risk factors in STEMI patients are currently limited. Method: Under analysis were 1,524 patients with STEMI who underwent primary percutaneous coronary intervention in the INTERSTELLAR registry. Patients were divided into HM (≥ 2 risk factors) and non-HM impairment groups. The primary outcome was in-hospital all-cause mortality, and the secondary outcome was 1-year all-cause mortality. Results: Of 1,524 patients, 214 (14.0%) and 1,310 (86.0%) patients were in the HM and non-HM impairment groups, respectively. Patients with HM impairment had a higher incidence of in-hospital mortality than those without (24.3% vs. 2.7%, p < 0.001). After adjusting for confounders, HM impairment was independently associated with in-hospital mortality (inverse probability of treatment weighting [IPTW]-adjusted odds ratio: 1.81, 95% confidence interval: 1.08–3.14). In the third door-to-balloon (DTB) time tertile (≥ 82 min), HM impairment was strongly associated with in-hospital mortality. In the first DTB time tertile ( < 62 min), indicating relatively rapid revascularization, HM impairment was consistently associated with increased in-hospital mortality. Conclusions: Hemo-metabolic impairment is significantly associated with increased risk of in-hospital and 1-year mortality in patients with STEMI. It remains a significant prognostic factor, regardless of DTB time

YH29407 with anti-PD-1 ameliorates anti-tumor effects via increased T cell functionality and antigen presenting machinery in the tumor microenvironment

Among cancer cells, indoleamine 2, 3-dioxygenase1 (IDO1) activity has been implicated in improving the proliferation and growth of cancer cells and suppressing immune cell activity. IDO1 is also responsible for the catabolism of tryptophan to kynurenine. Depletion of tryptophan and an increase in kynurenine exert important immunosuppressive functions by activating regulatory T cells and suppressing CD8+ T and natural killer (NK) cells. In this study, we compared the anti-tumor effects of YH29407, the best-in-class IDO1 inhibitor with improved pharmacodynamics and pharmacokinetics, with first and second-generation IDO1 inhibitors (epacadostat and BMS-986205, respectively). YH29407 treatment alone and anti-PD-1 (aPD-1) combination treatment induced significant tumor suppression compared with competing drugs. In particular, combination treatment showed the best anti-tumor effects, with most tumors reduced and complete responses. Our observations suggest that improved anti-tumor effects were caused by an increase in T cell infiltration and activity after YH29407 treatment. Notably, an immune depletion assay confirmed that YH29407 is closely related to CD8+ T cells. RNA-seq results showed that treatment with YH29407 increased the expression of genes involved in T cell function and antigen presentation in tumors expressing ZAP70, LCK, NFATC2, B2M, and MYD88 genes. Our results suggest that an IDO1 inhibitor, YH29407, has enhanced PK/PD compared to previous IDO1 inhibitors by causing a change in the population of CD8+ T cells including infiltrating T cells into the tumor. Ultimately, YH29407 overcame the limitations of the competing drugs and displayed potential as an immunotherapy strategy in combination with aPD-1

Results from the PARADIGM registry

Funding Information: This work was supported by the Korea Medical Device Development Fund grant funded by the Korean government (Ministry of Science and ICT; Ministry of Trade, Industry and Energy; Ministry of Health & Welfare, Republic of Korea; and Ministry of Food and Drug Safety; Project Number: 202016B02) and funded in part by a generous gift from the Dalio Institute of Cardiovascular Imaging and the Michael Wolk Foundation. This work was also supported by the National Research Foundation of Korea [RS‐2022‐00165404, 2022R1A5A6000840, 2020R1I1A1A01073151]. The funder of the study had no role in study design, data collection, data analysis, data interpretation, or writing of the report. Publisher Copyright: © 2023 The Authors. Clinical Cardiology published by Wiley Periodicals, LLC.Background and Hypothesis: The recently introduced Bayesian quantile regression (BQR) machine-learning method enables comprehensive analyzing the relationship among complex clinical variables. We analyzed the relationship between multiple cardiovascular (CV) risk factors and different stages of coronary artery disease (CAD) using the BQR model in a vessel-specific manner. Methods: From the data of 1,463 patients obtained from the PARADIGM (NCT02803411) registry, we analyzed the lumen diameter stenosis (DS) of the three vessels: left anterior descending (LAD), left circumflex (LCx), and right coronary artery (RCA). Two models for predicting DS and DS changes were developed. Baseline CV risk factors, symptoms, and laboratory test results were used as the inputs. The conditional 10%, 25%, 50%, 75%, and 90% quantile functions of the maximum DS and DS change of the three vessels were estimated using the BQR model. Results: The 90th percentiles of the DS of the three vessels and their maximum DS change were 41%–50% and 5.6%–7.3%, respectively. Typical anginal symptoms were associated with the highest quantile (90%) of DS in the LAD; diabetes with higher quantiles (75% and 90%) of DS in the LCx; dyslipidemia with the highest quantile (90%) of DS in the RCA; and shortness of breath showed some association with the LCx and RCA. Interestingly, High-density lipoprotein cholesterol showed a dynamic association along DS change in the per-patient analysis. Conclusions: This study demonstrates the clinical utility of the BQR model for evaluating the comprehensive relationship between risk factors and baseline-grade CAD and its progression.publishersversionepub_ahead_of_prin

OGLE-2016-BLG-1227L: A Wide-separation Planet from a Very Short-timescale Microlensing Event

We present the analysis of the microlensing event OGLE-2016-BLG-1227. The light curve of this short-duration event appears to be a single-lens event affected by severe finite-source effects. Analysis of the light curve based on single-lens single-source (1L1S) modeling yields very small values of the event timescale, t_E ∼ 3.5 days, and the angular Einstein radius, θ_E ∼ 0.009 mas, making the lens a candidate of a free-floating planet. Close inspection reveals that the 1L1S solution leaves small residuals with amplitude ΔI ≲ 0.03 mag. We find that the residuals are explained by the existence of an additional widely-separated heavier lens component, indicating that the lens is a wide-separation planetary system rather than a free-floating planet. From Bayesian analysis, it is estimated that the planet has a mass of _p = 0.79^(+1.30)_(−0.39) M_J and it is orbiting a low-mass host star with a mass of M_(host) = 0.10+0.17−0.05 M_⊙ located with a projected separation of a_ = 3.4^(+2.1)_(−1.0) au. The planetary system is located in the Galactic bulge with a line-of-sight separation from the source star of D_(LS) = 1.21^(+0.96)_(−0.63) kpc. The event shows that there are a range of deviations in the signatures of host stars for apparently isolated planetary lensing events and that it is possible to identify a host even when a deviation is subtle