Citations

ABSTRACTIntroductionLow body weight in patients with COPD is associated with a poor prognosis and more comorbidities. However, the impact of increased body weight in patients with COPD remains controversial. The aim of this study was to explore the clinical features of overweight patients with AECOPD.MethodsIn this multicenter cross‐sectional study, a total of 647 AECOPD patients were recruited. Finally, 269 normal weight and 162 overweight patients were included. Baseline characteristics and clinical and laboratory data were collected. The least absolute shrinkage and selection operator (LASSO) regression was performed to determine potential features, which were substituted into binary logistic regression to reveal overweight‐associated clinical features. The nomogram and its associated curves were established to visualize and verify the logistic regression model.ResultsSix potential overweight‐associated variables were selected by LASSO regression. Subsequently, a binary logistic regression model identified that the rates of type 2 diabetes (T2DM) and hypertension and levels of lymphocytes (LYM)%, and alanine aminotransferase (ALT) were independent variables of overweight in AECOPD patients. The C‐index and AUC of the ROC curve of the nomogram were 0.671 and 0.666, respectively. The DCA curve revealed that the nomogram had more clinical benefits if the threshold was at a range of 0.22~0.78.ConclusionsCollectively, we revealed that T2DM and hypertension were more common, and LYM% and ALT were higher in AECOPD patients with overweight than those with normal weight. The result suggests that AECOPD patients with overweight are at risk for additional comorbidities, potentially leading to worse outcomes.

Abstract Cardioneuroablation has emerged as a potential alternative to cardiac pacing in selected cases with vasovagal reflex syncope, extrinsic vagally induced sinus bradycardia-arrest or atrioventricular block. The technique was first introduced decades ago, and its use has risen over the past decade. However, as with any intervention, proper patient selection and technique are a prerequisite for a safe and effective use of cardioneuroablation therapy. This document aims to review and interpret available scientific evidence and provide a summary position on the topic.

3579 Background: Fruquintinib (F) is a highly selective, oral tyrosine kinase inhibitor of all 3 VEGF receptors. Based on FRESCO (NCT02314819) and FRESCO-2 (NCT04322539) data, F was approved by the US FDA for previously treatedmetastatic colorectal cancer (mCRC). Efficacy and safety of F + best supportive care (BSC) vs placebo (P) + BSC were analyzed according to prior treatment (tx) sequence using FRESCO and FRESCO-2 data. Methods: In FRESCO and FRESCO-2, patients (pts) were randomized 2:1 to receive F 5 mg or matching P, PO daily x 21 days every 28 days. In FRESCO, eligible pts had received ≥2 prior chemotherapy regimens and were permitted to have received prior anti-VEGF and/or anti-EGFR therapies, whereas in FRESCO-2, in addition to standard chemotherapies, anti-VEGF, and anti-EGFR therapies if indicated, prior exposure to trifluridine/tipiracil (TAS) and/or regorafenib (rego) was required. FRESCO-2 pts must have also received a BRAF inhibitor and/or immunotherapy, if indicated and available in their country. Results: In FRESCO (F n=278 vs P n=138), no pts had received rego and 16/416 pts (4%) had received TAS. InFRESCO-2, prior therapies were balanced between F vs P arms; pts had received prior TAS or rego in these sequences: prior TAS only (n=240 vs n=121); prior rego only (n=40 vs n=18); prior rego then TAS (n=84 vs n=45); prior TAS then rego (n=95 vs n=44). Improvements in OS and PFS were seen with F vs P regardless of prior tx sequence (Table), with similar magnitudes of benefit for OS (HRs 0.53–0.77) and PFS (HRs 0.25–0.37). F safety profile was consistent regardless of prior tx sequence (Table). Conclusions: F is effective in mCRC with a manageable safety profile regardless of prior TAS or rego tx and sequence. Improvement with F was similar for OS and PFS despite the number and sequence of prior regimens. F provides a new tx option for pts with previously treated mCRC regardless of prior TAS or rego exposure. Clinical trial information: NCT04322539 . [Table: see text]

AbstractYao syndrome (YAOS) is a novel systemic autoinflammatory disease linked to the nucleotide‐binding oligomerization domain (NOD2) gene. It is characterized by periodic fevers, gastrointestinal (GI) symptoms, arthritis, and dermatitis, among other symptoms. A sparse literature exists on this disease, and little is known about its dermatological manifestations. A review of available literature was performed to characterize the cutaneous manifestations of Yao syndrome. Cutaneous manifestations were documented in 85.7% of patients, with common characteristic descriptions of erythematous patches and plaques involving the face, trunk, abdomen, and extremities. Based on our review of treatment modalities employed for Yao syndrome, prednisone is an appropriate initial approach, with oral sulfasalazine and other disease‐modifying antirheumatic drugs serving as appropriate secondary options. YAOS should be considered in the differential diagnosis of patients presenting with a dermatitic rash, especially in the context of concurrent articular symptoms, periodic fever, and GI symptoms.

The effectiveness of coronavirus disease 2019 (COVID-19) vaccines against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) strain rapidly wanes over time. Growing evidence from epidemiological studies suggests that influenza vaccination is associated with a reduction in the risk of SARS-CoV-2 infection and COVID-19 severity. However, the underlying mechanisms remain elusive. Here, we investigate the cross-reactive immune responses of influenza vaccination to SARS-CoV-2 spike protein peptides based on in vitro study. Our data indicate enhanced activation-induced-marker (AIM) expression on CD4+ T cells in influenza-vaccination (IV)-treated peripheral blood mononuclear cells (PBMCs) upon stimulation with spike-protein-peptide pools. The fractions of other immune cell subtypes, including CD8+ T cells, monocytes, NK cells, and antigen-presenting cells, were not changed between IV-treated and control PBMCs following ex vivo spike-protein-peptide stimulation. However, the classical antiviral (IFN-γ) and anti-inflammatory (IL-1RA) cytokine responses to spike-protein-peptide stimulation were still enhanced in PBMCs from both IV-immunized adult and aged mice. Decreased expression of proinflammatory IL-1β, IL-12p40, and TNF-α is associated with inhibited levels of histone acetylation in PBMCs from IV-treated mice. Remarkably, prior immunity to SARS-CoV-2 does not result in modification of histone acetylation or hemagglutinin-protein-induced cytokine responses. This response is antibody-independent but can be mediated by manipulating the histone acetylation of PBMCs. These data experimentally support that influenza vaccination could induce modification of histone acetylation in immune cells and reveal the existence of potential cross-reactive immunity to SARS-CoV-2 antigens, which may provide insights for the adjuvant of influenza vaccine to limit COVID-19-related inflammatory responses.

Background The study aimed to describe the patterns and trends of initiation, discontinuation, and adherence of oral anticoagulation (OAC) in patients with new‐onset postoperative atrial fibrillation (POAF), and compare with patients newly diagnosed with non‐POAF. Methods and Results This retrospective cohort study identified patients newly diagnosed with atrial fibrillation or flutter between 2012 and 2021 using administrative claims data from OptumLabs Data Warehouse. The POAF cohort included 118 366 patients newly diagnosed with atrial fibrillation or flutter within 30 days after surgery. The non‐POAF cohort included the remaining 315 832 patients who were newly diagnosed with atrial fibrillation or flutter but not within 30 days after a surgery. OAC initiation increased from 28.9% to 44.0% from 2012 to 2021 in POAF, and 37.8% to 59.9% in non‐POAF; 12‐month medication adherence increased from 47.0% to 61.8% in POAF, and 59.7% to 70.4% in non‐POAF. The median time to OAC discontinuation was 177 days for POAF, and 242 days for non‐POAF. Patients who saw a cardiologist within 90 days of the first atrial fibrillation or flutter diagnosis, regardless of POAF or non‐POAF, were more likely to initiate OAC (odds ratio, 2.92 [95% CI, 2.87–2.98]; P <0.0001), adhere to OAC (odds ratio, 1.08 [95% CI, 1.04–1.13]; P <0.0001), and less likely to discontinue (odds ratio, 0.83 [95% CI, 0.82–0.85]; P <0.0001) than patients who saw a surgeon or other specialties. Conclusions The use of and adherence to OAC were higher in non‐POAF patients than in POAF patients, but they increased over time in both groups. Patients managed by cardiologists were more likely to use and adhere to OAC, regardless of POAF or non‐POAF.

Abstract Background Tumor microenvironment (TME) characteristics including tumor stroma ratio (TSR), tumor budding (TB), and tumor-infiltrating lymphocytes (TILs) were examined in resected gastric cancer. These TME features have been shown to indicate metastatic potential in colon cancer, and intestinal-type gastric cancer (IGC) has pathological similarities with that malignancy. Methods TSR, TB, and TILs were quantified in routine histological sections from 493 patients with IGC who underwent radical resection at 2 university hospitals in China from 2010 to 2016. TME variables were dichotomized as follows: TSR (50%), TILs (median), TB per international guidelines (4 buds/0.785mm2), and platelet-lymphocyte ratio (PLR) per survival ROC. Association of TME features with patient clinicopathological characteristics, time-to-recurrence (TTR), and cancer-specific-survival (CSS) were examined using univariate and multivariate analysis, including a relative contribution analysis by Cox regression. Results Patients whose tumors showed high TSR or high TB or low TILs were each significantly associated with increased T and N stage, higher histological grade, and poorer TTR and CSS at 5 years. Only TSR and N stage were independently associated with TTR and CSS after adjustment for covariates. PLR was only independently associated with TTR after adjustment for covariates. Among the variables examined, only TSR was significantly associated with both TTR (HR 1.72, 95% CI, 1.14-2.60, P = .01) and CSS (HR 1.62, 95% CI, 1.05-2.51, P = .03) multivariately. Relative contribution to TTR revealed that the top 3 contributors were N stage (45.1%), TSR (22.5%), and PLR (12.9%), while the top 3 contributors to CSS were N stage (59.9%), TSR (14.7%), and PLR (10.9%). Conclusions Among the examined TME features, TSR was the most robust for prognostication and was significantly associated with both TTR and CSS. Furthermore, the relative contribution of TSR to patient TTR and CSS was second only to nodal status.

Abstract Isolation of neuron‐derived extracellular vesicles (NDEVs) with L1 Cell Adhesion Molecule (L1CAM)‐specific antibodies has been widely used to identify blood biomarkers of CNS disorders. However, full methodological validation requires demonstration of L1CAM in individual NDEVs and lower levels or absence of L1CAM in individual EVs from other cells. Here, we used multiple single‐EV techniques to establish the neuronal origin and determine the abundance of L1CAM‐positive EVs in human blood. L1CAM epitopes of the ectodomain are shown to be co‐expressed on single‐EVs with the neuronal proteins β‐III‐tubulin, GAP43, and VAMP2, the levels of which increase in parallel with the enrichment of L1CAM‐positive EVs. Levels of L1CAM‐positive EVs carrying the neuronal proteins VAMP2 and β‐III‐tubulin range from 30% to 63%, in contrast to 0.8%–3.9% of L1CAM‐negative EVs. Plasma fluid‐phase L1CAM does not bind to single‐EVs. Our findings support the use of L1CAM as a target for isolating plasma NDEVs and leveraging their cargo to identify biomarkers reflecting neuronal function.