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Background: Arteriovenous malformations (AVMs) are complex vascular anomalies with a high risk of hemorrhage and neurological deficits, especially when located in eloquent brain regions. The eloquence of an AVM location is a critical factor in the treatment planning, influencing both the risk of complications and long-term functional outcomes. This study aims to compare outcomes between eloquent and non-eloquent AVMs. Methods: This multicenter, retrospective study utilized data from the Multicenter International Study for Treatment of Brain AVMs (MISTA) consortium. Patients with eloquent and non-eloquent AVMs were compared on baseline characteristics, angiographic outcomes, and functional outcomes using the modified Rankin Scale (mRS). Propensity score weighting (IPTW) was applied to adjust for confounding variables. Results: The study included 1013 patients, with 498 (49.2%) AVMs located in eloquent regions and 515 (50.8%) in non-eloquent regions. In unadjusted analysis, eloquent AVMs had lower complete obliteration rates (67.6% vs 79.5%, OR: 0.53, 95% CI: 0.39–0.72, p < 0.001) and higher complication rates (24.5% vs 19.0%, OR: 1.38, 95% CI: 1.02–1.86, p = 0.03) compared to non-eloquent AVMs. After IPTW adjustment, eloquent AVMs continued to show significantly higher odds of overall complications (OR: 1.68, 95% CI: 1.12–2.52, p = 0.01) and symptomatic complications (OR: 1.77, 95% CI: 1.12–2.80, p = 0.01). Secondary analysis within the eloquent group indicated that embolization was linked to an elevated risk of complications. Surgery and radiosurgery showed comparable functional outcomes at last follow-up and complications rates with higher complete obliteration rates in surgery. Conclusion: AVMs in eloquent brain areas present higher risks of complications and lower obliteration rates, emphasizing the need for cautious, individualized treatment planning. Within the eloquent group, embolization increased the risk of complications, while surgery and radiosurgery showed comparable functional outcomes at last follow-up and complication rates with higher complete obliteration rates in surgery. These findings highlight the importance of location in AVM management and support further research focusing on comparing treatment strategies for AVMs in eloquent brain areas.

ABSTRACTIntroductionLung transplantation has been evolving since its inception in 1963. Over recent years, literature has suggested a shift in the perioperative strategy of mechanical support toward extracorporeal membrane oxygenation (ECMO) as the preferred modality of extracorporeal life support (ECLS) in lung transplantation. The Survey of ECLS Application in Lung transplantation (SEAL) was designed to elucidate the current practice patterns of perioperative ECLS within the United States.MethodsIn this cross‐sectional study, a physician from 62 adult lung transplantation centers across the United States of America (USA) was surveyed on their institutional practices regarding the perioperative management of lung transplantation patients, with a focus on mechanical support.ResultsThe survey completion rate was 74% (46/62 eligible institutions). Most transplant centers utilize venoarterial (VA) ECMO (78%, 36/46) and/or venovenous (VV) ECMO (93%, 29/43) as a bridge to lung transplantation. When ECLS is used intraoperatively, 61% of (28/46) responding programs use VA ECMO as their preferred support. All programs use transesophageal echocardiography (TEE) intraoperatively, 85% (33/39) cannulate for ECMO centrally, and 74% (29/39) use a combination of inhaled and intravenous anesthesia while using ECMO intraoperatively. Most programs do not use antifibrinolytic during VA ECMO (62%, 28/45). Anticoagulation management and VA ECMO flows throughout the procedure showed considerable variation.ConclusionData from SEAL illustrates that though there are some practice commonalities within the United States, there is also quite a bit of variability in practice. Multiple dominant practices within the USA are consistent with a recently published International Society of Heart and Lung Transplantation consensus.

Background Brain arteriovenous malformations (AVMs) are abnormal connections between feeding arteries and draining veins, associated with significant risks of haemorrhage, seizures and other neurological deficits. Preoperative embolization is commonly used as an adjunct to microsurgical resection, with the aim of reducing intraoperative complications and improving outcomes. However, the efficacy and safety of this approach remain controversial. Methods This study is a subanalysis of the Multicenter International Study for Treatment of Brain AVMs consortium. We retrospectively analysed 486 patients with brain AVMs treated with microsurgical resection between January 2010 and December 2023. Patients were divided into two groups: those who underwent microsurgery alone (n=245) and those who received preoperative embolization, followed by microsurgery (n=241). Propensity score matching was employed, resulting in 288 matched patients (144 in each group). The primary outcomes were rates of complete AVM obliteration and functional outcomes (measured by the modified Rankin Scale (mRS)). Secondary outcomes included complication rates, mortality, hospital length of stay and postsurgical rupture. Results After matching, the complete obliteration rate was 97% with no significant difference between the microsurgery-only group and the preoperative embolization group (p=0.12). The proportion of patients with an mRS score of 0–2 at the last follow-up was similar in both groups (83% vs 84%; p=0.67). The median hospital stay was significantly longer for the embolisation group (9 days vs 7 days; p=0.017). Complication rates (24% vs 22%; p=0.57) and mortality rates (4.9% vs 2.1%; p=0.20) were comparable between the two groups. No significant differences were observed in postsurgical rupture, recurrence or retreatment rates. Conclusions In this large multicentre study, preoperative embolization did not significantly improve AVM obliteration rates, functional outcomes or reduce complications compared with microsurgery alone.

AbstractAutoimmune pancreatitis (AIP) is identified as a severe chronic immune‐related disorder in pancreas, including two subtypes. In this study, pancreatic lesions in patients diagnosed as either type 1 AIP or type 2 AIP are examined, and these patients’ peripheral blood at single‐cell level. Furthermore, flow cytometry, immunofluorescence, and functional assays are performed to verify the identified cell subtypes. In type 1 AIP, there is a notable increase in the amount of B cells and plasma cells, and IgG4+ plasma cells are key pathogenic cells of AIP. The differentiation path of naïve‐stage B cells into IgG4+ produced plasma cells is observed, and an increased amount of T helper cells and T follicular helper (Tfh) cells. This study also reveals that HIF‐1α, an activated transcriptional factor, can directly bind to promoter site of NAMPT, promoting higher levels of visfatin production in HIF1A+ classical monocytes. Pancreatic stellate cells can be activated by extracellular visfatin and promote the development of fibrotic response in pancreatic lesions across both AIP subtypes. The current findings shed light on the exploration of dynamic alterations in peripheral blood cells and cell subgroups in pancreatic lesions of AIP, while elucidating a pathogenic cell subset and potential fibrosis mechanism of AIP.

608 Background: Tinengotinib, a spectrum-selective multi-kinase inhibitor with unique binding properties to FGFR , potently inhibited FGFR2 fusion/rearrangement and acquired resistant/gatekeeper mutations in pre-clinical models and exhibited antitumor activity in cholangiocarcinoma (CCA) patients (pts) in phase 1/2 trials. Here we present the overall survival (OS) data and biomarker correlative analysis from a phase 2 clinical trial of tinengotinib in CCA. Methods: Eligible pts with advanced/metastatic CCA who had received ≥ 1 prior systemic chemotherapy with ECOG PS 0-1 were treated with tinengotinib 10 mg QD across four Cohorts: A1: FGFR2 fusion(s) with primary progression on previous FGFR inhibitor ( FGFR i); A2: FGFR2 fusion(s) with progression after prior response to FGFR i; B: FGFR alteration(s) without FGFR2 fusion(s); C: FGFR wild-type. Efficacy was evaluated per RECIST v1.1 and safety was assessed by CTCAE v5.0. Genomic alterations in circulating tumor DNA (ctDNA) were assessed by Foundation Medicine NGS panel at baseline, C3D1 and EOT. Planned correlative analyses of response (PR+SD>6 months) and PFS in pt subgroups based on ctDNA mutational status were performed. Results: 55 eligible pts were enrolled (18 in A1, 11 in A2, 13 in B, 13 in C) with median age 61.0 [range 24-81] years, ECOG PS 0 in 50.9% pts, 56.4% female, and 60.0% with ≥ 3 lines of prior therapy. Among 42 pts with FGFR alterations, 78.4% had ≥ 1 prior FGFR i, and 97.6% had prior chemotherapy. Median follow up time was 8.6 months (0.4-30.5). The median OS (months) was 17.1 (95%CI 7.5-19.5) in A1; not reached (95%CI 9.6, -) in A2; 18.0 (95%CI 9.6, -) in A1+A2; not reached (95%CI 8.0, -) in B; 6.5 (95%CI 4.8-16.4) in C. The OS rate in A, B and C was 100%, 91.7% and 75% at month 3; 83.7%, 83.3% and 66.7% at month 6, and 65.8%, 55.6% and 23.8% at month 12. Partial response was observed in 26% (10/39) of evaluable FGFR-altered pts (A1+A2+B). The safety profile was consistent with previous reports. The most common any-grade treatment-related AEs were hypertension (63.6%) and diarrhea (47.3%). Baseline ctDNA results were available in 46 pts, 35 in cohorts A+B and 11 in C. A positive correlation was shown in MED12 mutation vs response (P=0.03476). BCOR and ARID1A mutation were found to be negatively associated with PFS (P=0.01366 and P=0.0437). Acquired/secondary mutations at baseline were observed in cohort A, including V564F/I (3/24 and 5/24) and N549K/H (5/24 and 5/24); favorable anti-tumor activity was noted despite these resistant mutations, consistent with preclinical data. Conclusions: Tinengotinib has shown promising anti-tumor efficacy in CCA pts with FGFR fusion after prior FGFR i and in those with primary FGFR mutations. An ongoing randomized phase III study will investigate tinengotinib vs. chemotherapy in FGFR inhibitor refractory CCA (NCT05948475). Clinical trial information: NCT04919642 .

AbstractBackgroundCerebral small vessel disease (cSVD), as defined by neuroimaging characteristics such as white matter hyperintensities (WMHs), cerebral microhemorrhages (CMHs), and lacunar infarcts, is highly prevalent and has been associated with dementia risk and other clinical sequelae. Although risk factors for cSVD have been identified, little is known about the biological processes and molecular mediators that influence cSVD development and progression.MethodsWithin the Atherosclerosis Risk in Communities (ARIC) study, we used SomaScan Multiplexed Proteomic technology to relate 4,877 plasma proteins to concurrently measured MRI‐defined cSVD characteristics, including WMHs, CMHs, and lacunar infarcts, in late‐life (n=1508; mean age: 76). Candidate protein associations with WMH volume were replicated in the Cardiovascular Health Study (n=765; mean age: 73) and Baltimore Longitudinal Study of Aging (n=902; mean age: 66). Cohort‐specific effect estimates were pooled using a fixed‐effect, inverse variance weighted meta‐analysis. Within 4228 non‐demented older adults in ARIC, we examined the association of WMH‐associated proteins with eight‐year dementia risk (641 incident dementia cases) using multivariate Cox proportional hazard models. All multivariate regression models were adjusted for demographic, kidney function, and cardiovascular risk variables.ResultsThis proteome‐wide analysis of older adults identified 13 WMH‐associated plasma proteins involved in synaptic function, endothelial integrity, and angiogenesis (Figures 1a, 2a). Nine of these proteins replicated in one or more external cohort (Figures 1b, 2b) and two proteins, oligodendrocyte myelin glycoprotein (OMG) and neuronal pentraxin receptor (NPTXR), remained associated with late‐life WMH volume when measured nearly two decades earlier during midlife (Figures 1c, 2c). Eight of the 13 WMH‐associated proteins were associated with lacunar infarcts, 6 with subcortical CMHs, and 4 with lobar CMHs (Figures 1d, 2d). Although none of the genes coding for WMH‐associated proteins have been nominated by WMH GWAS, 7 of these genes have been previously linked to cardiometabolic traits known to influence cSVD, such as blood pressure and cholesterol (Figures 1e, 2e). Finally, 11 candidate proteins were associated with incident dementia, underscoring their clinical relevance (Figures 1f, 2f).ConclusionsThis large‐scale proteomic analysis within longitudinal community‐based samples identified several plasma proteins, including OMG and NPTXR, as top candidate biomarkers for elevated WMH volume and its clinical manifestations.

Oral squamous cell carcinoma (OSCC) is one of the most common malignancies of the head and neck squamous cell carcinoma (HNSCC). HNSCC is recognized as the eighth most commonly occurring cancer globally in men. It is essential to distinguish between cancers arising in the head and neck regions due to significant differences in their etiologies, treatment approaches, and prognoses. As the Cancer Genome Atlas (TCGA) dataset is available in HNSCC, the survival analysis prognosis of OSCC patients based on the TCGA dataset for discovering gene expression-based prognostic biomarkers is limited. To address this paucity, we aimed to provide comprehensive evidence by recruiting studies that have reported new biomarkers/signatures to establish a prognostic model to predict the survival of OSCC patients. Using PubMed search, we have identified 34 studies that have been using the least absolute shrinkage and selection operator (LASSO)-based Cox regression analyses to establish signature prognosis that related to different pathways in OSCC from the past 4 years. Our review was focused on summarizing these signatures and implications for targeted therapy using FDA-approved drugs. Furthermore, we conducted an analysis of the LASSO Cox regression gene signatures. Our findings revealed 13 studies that correlated a greater number of regulatory T cells (Tregs) cells in protective gene signatures with increased recurrence-free and overall survival rates. Conversely, two studies displayed an opposing trend in cases of OSCC. We will also explore how the dysregulation of these signatures impacts immune status, promoting tumor immune evasion or, conversely, enhancing immune surveillance. Overall, this review will provide new insight for future anti-cancer therapies based on the potential gene that is associated with poor prognosis in OSCC.

ABSTRACTBackgroundThe role of Intravascular ultrasound (IVUS) and optical coherence tomography (OCT) is still unclear in patients with STEMI undergoing PCI in the current second‐generation DES era.AimsThis study aimed to evaluate the trends and outcomes of IVUS‐guided PCI in patients with STEMI.MethodsWe used the National Inpatient Sample (NIS) database from 2016 to 2021. The primary endpoint of this study is all‐cause in‐hospital mortality. Secondary endpoints include trends of PCI hospitalizations, trends of mortality, length of stay, and cost of hospitalization.ResultsThere were data for 819,645 hospitalizations for STEMI, of which 91.2% (n = 74,7860) utilized angiography‐guided PCI, 8.4% (n = 68,985) utilized IVUS‐guided PCI and 0.3% (n = 2800) utilized OCT‐guided PCI. In‐hospital mortality for IVUS‐guided PCI was 4.6% (n = 3190) versus 6.0% (n = 44,935) for angiography‐guided PCI with an adjusted OR 0.75 (0.68–0.81, p < 0.001). In‐hospital mortality for OCT‐guided PCI was 3.4% (n = 95) versus 6.0% (n = 44,935) for angiography‐guided PCI with an adjusted OR 0.67 (0.43–1.06, p = 0.09).ConclusionsIVUS/OCT‐guidance was increasingly utilized over the years and was associated with a significantly reduced adjusted odds of in‐hospital mortality. Large‐scale, long‐term randomized data are needed to better ascertain where IVUS/OCT may be best utilized for optimization of PCI for STEMI.