The alternative splice isoform of pyruvate kinase M (PKM), PKM2, plays a pivotal role in regulating aerobic glycolysis in tumor cells. Systemic delivery of antisense oligonucleotides (ASOs) that shift PKM splicing from the PKM2 isoform to the PKM1 isoform inhibits tumor progression and reprograms intratumoral metabolism. However, the cellular populations within the tumor microenvironment (TME) are also highly dependent on PKM2 and might likewise be affected by ASO treatment. In this study, we demonstrate that PKM2 is upregulated and PKM1 is downregulated in both human and murine pancreatic ductal adenocarcinoma (PDAC) cells. PKM1 and PKM2 are mutually exclusive and expressed in a cell type-specific manner in various cell types and stages of PDAC tumors. We report that basal-like PDAC cells and their surrounding activated regulatory T cells (Tregs) rely on PKM2 to sustain glycolysis. Although PKM-ASO monotherapy had a limited effect in an immunodeficient mouse model of PDAC, synergy between PKM-ASO and anti-CTLA-4 immune checkpoint blockade (ICB), which targets Tregs, restricted tumor growth in an immunocompetent mouse model. Our findings provide preclinical support for combined antisense therapy and ICB for PDAC patients, highlighting the critical role of PKM2 in the TME and its potential as a therapeutic target.

Limited evidence exists regarding predictors of recurrence in patients with non-valvular atrial fibrillation (NVAF) following radiofrequency catheter ablation (RFCA). This study aimed to develop and validate a risk model for post-ablation recurrence in these patients. 242 patients were enrolled and randomly divided into a modeling group (n = 169) and a validation group (n = 73) according to 7:3. The echocardiographic parameters, laboratory values and clinical features were used to derive a predictive model. Univariate and multivariate logistic regression analyses were used to identify independent risk factors. During the 1-year follow-up, 87(36.00

BACKGROUND & OBJECTIVES:Incomplete endothelialization of the left atrial appendage(LAA) occluder potentially affects the long-term efficacy of stroke prevention in atrial fibrillation(AF) patients. This study aims to explore the value of routine preoperative transthoracic echocardiography(TTE) in predicting the endothelialization of Watchman LAA occluder. METHODS:This single-center retrospective study included 437 AF patients who underwent the LAA closure with Watchman 2.5 occluder from January 2017 to December 2022. Cardiac CTA was performed 3-6 months after the procedure. Based on contrast infiltration into the LAA cavity, two groups were defined as follows: completely and incompletely endothelialized. The baseline and pre-procedural TTE parameters were analyzed. RESULTS:The average age was 70.2 years old, with 208 females(47.6 %). The incompletely endothelialized group had an older age (71.4 ± 7.5 vs 69.8 ± 7.6,p = 0.053), a larger left atrial(LA) diameter (44.0 ± 5.9 vs 42.7 ± 6.1 mm,p = 0.045) and a lower left ventricular ejection fraction(LVEF%)(62.5 ± 7.5 vs 63.0 ± 5.4 %,p = 0.016) than the completely endothelialized group. Univariate analysis revealed that incomplete endothelialization was associated with persistent AF(OR:1.68;95 % CI:1.08-2.10;p = 0.021), a higher LA diameter(OR:1.04;95 % CI:1.00-1.07;p = 0.046), a higher left ventricular diastolic diameter(LVDD)(OR:1.05;95 % CI:1.00-1.10;p = 0.032),and the presence of mild mitral stenosis (mean pressure gradient <5 mmHg and mitral valve area > 1.5 cm2,OR:11.29;95 % CI:1.25-102.10;p = 0.031), while it was negatively correlated with mild left ventricular diastolic dysfunction (OR:0.49;95 % CI:0.26-0.94;p = 0.033). Multivariate analysis demonstrated that mild mitral stenosis(OR: 13.79;95 % CI:1.37-139.13;p = 0.026) was an independent predictor for incomplete endothelialization. CONCLUSION:Preoperative TTE may predict the outcomes of endothelialization after left atrial appendage occlusion. Mild or severe mitral stenosis is an independent predictive factor for poor endothelial coverage.

Metastasis is the leading cause of death for nearly 90% of patients with cancer. In the digestive system, malignancies preferentially metastasize to the liver, which occurs in 76-80% of patients with pancreatic ductal adenocarcinoma (PDAC). Given the shared endoderm origin of embryonic pancreas and liver, this study investigated whether genes highly expressed in liver progenitors drive PDAC cells metastasize to the liver. Using an in vitro liver differentiation model, genes highly expressed in liver progenitors were identified. Among them, TFAP2A was highly expressed in PDAC and closely related to PDAC liver metastasis. Cancer associated fibroblasts (CAFs) upregulated TFAP2A expression by bone morphogenetic protein 4 (BMP4). Functional experiments demonstrated that TFAP2A overexpression promoted PDAC cell stemness and liver metastasis in vitro and in vivo. Mechanistically, TFAP2A could promote epithelial mesenchymal transition (EMT) and recruit macrophage by upregulating MYC, facilitating PDAC cell intravasation. Collectively, these findings unveil molecular mechanisms for PDAC liver metastasis and potential therapeutic targets.

Purpose:To utilize the developed nomogram for evaluating the risk of recurrence in non-valvular atrial fibrillation (NVAF) patients after radiofrequency catheter ablation (RFCA) and compare the model's performance with the APPLE, ATLAS, and Antwerp scores. Patients and Methods:242 patients with NVAF requiring RFCA were enrolled. These patients were randomly divided into a training cohort (n=169) and a validation cohort (n=73) according to 7:3. A nomogram was developed based on LAVI, RAVI, SII, NYHA classification, CHA2DS2-VASc score to estimate the risk of AF recurrence after RFCA. The APPLE, ATLAS, and Antwerp scores were calculated using the "pROC" package in R software. The AUC value of the nomogram compared with each of the three scores was evaluated using the DeLong test. The integrated discrimination improvement and net reclassification index were calculated to compare the predictive performance of the nomogram against the scores in R software. Results:The nomogram achieved significantly higher values with an AUC of 0.837 (95% CI: 0.774-0.899) in the training cohort and 0.895 (95% CI: 0.823-0.968) in the validation cohort (all P < 0.05) than the three scores. It also achieved better positive and negative predictive values, indicating enhanced discriminatory power. By integrating multidimensional parameters and optimizing risk stratification, it significantly reduced misjudgment rates. Furthermore, the model demonstrated a more balanced sensitivity-specificity profile and greater predictive stability than single-dimensional scores. It also provides more robust clinical decision support for predicting post-RFCA recurrence across diverse datasets. Conclusion:The APPLE, ATLAS, and Antwerp scores all demonstrated effectiveness in predicting AF recurrence after RFCA in patients with NVAF. Among these established scoring systems, the APPLE score showed better performance compared to the other two. More importantly, our newly developed nomogram exhibited superior performance compared to all three existing scores, demonstrating a marked improvement in predicting the risk of AF recurrence. While our model represents a promising tool, it is still in the preliminary stage and requires further validation in larger, multi-center, prospective cohorts to confirm its generalizability.

Pancreatic ductal adenocarcinoma (PDAC) ranks as third leading cause of cancer-related mortality, with chemoresistance progression driven by the desmoplastic extracellular matrix (ECM). Hyaluronic acid (HA), one of the major components of ECM, is notably enriched in PDAC. HA-based strategies, like lowering HA levels with a hyaluronidase, are worthy of experimental evidence for PDAC. Our previous work identified CEMIP2 (Cell migration inducing hyaluronidase 2) as a proteomic biomarker predictive of adjuvant chemotherapy response in PDAC, though its mechanistic role remains unclear. Herein, we observed that elevated CEMIP2 expression correlates with improved patient response to neoadjuvant and adjuvant chemotherapy. Using PDAC murine models, we reveal that CEMIP2 enhances gemcitabine efficacy through HA-dependent mechanisms involving drug delivery potentiation and vascular density modulation, attributable to its HA-degrading capacity. Consistent with this, CEMIP2 expression shows an inverse correlation with HA levels in clinical PDAC specimens, while low HA levels themselves associate with favorable treatment response and survival outcomes. Single-cell RNA sequencing (scRNA-seq) uncovered that CEMIP2 knockdown alters the tumor microenvironment (TME) by expanding cancer-associated fibroblast (CAF) populations. Both inflammatory (iCAF) and myofibroblast (myCAF) subtypes exhibited SPP1-CD44-mediated crosstalk with PDAC cells. Additionally, cytometry by time-of-flight (CyTOF) revealed that CEMIP2 depletion modulates the abundance and functional states of immune subsets, particularly tumor-associated macrophages (TAMs) and T cell populations. Collectively, our findings establish CEMIP2 as a critical regulator of chemotherapy response that reprograms the TME through HA degradation and ECM remodeling, providing novel insights into PDAC treatment resistance mechanisms.

Systemic light chain amyloidosis is a rare and debilitating disease, especially for which initially presented with digestive tract involvement. Myocardial amyloidosis is highly aggressive with generally poor prognosis and often resulted in missed diagnosis or misdiagnosis with routine examination tools. Multimodality imaging play an important role in diagnosing the amyloidosis effect on multiple organs. Chemoradiotherapy is the mainstay of treatment. This article presents a rare case of systemic light chain amyloidosis, initially with gastrointestinal symptoms, in a 68-year-old male. He was hospitalized with diarrhea for one year and a half, dysphagia for 4 months, but he had no dyspnea. The transthoracic echocardiogram revealed myocardial hypertrophy of the left ventricle, the hypertrophic heart muscle echoed like "ground glass". The left ventricular ejection fraction (LVEF) detected by Simpson method was 51

BACKGROUND:Breast cancer is the most common malignant tumor among women worldwide, and early diagnosis is crucial for reducing mortality rates. Traditional diagnostic methods have significant limitations in terms of accuracy and consistency. Imaging is a common technique for diagnosing and predicting breast cancer, but human error remains a concern. Increasingly, artificial intelligence (AI) is being employed to assist physicians in reducing diagnostic errors. METHODS:We developed an intelligent diagnostic model combining deep learning and radiomics to enhance breast tumor diagnosis. The model integrates MobileNet with ResNeXt-inspired depthwise separable and grouped convolutions, improving feature processing and efficiency while reducing parameters. Using AI-Dhabyani and TCIA breast ultrasound datasets, we validated the model internally and externally, comparing it to VGG16, ResNet, AlexNet, and MobileNet. Results: The internal validation set achieved an accuracy of 83.84% with an AUC of 0.92, outperforming other models. The external validation set showed an accuracy of 69.44% with an AUC of 0.75, demonstrating high robustness and generalizability. Conclusions: We developed an intelligent diagnostic model using deep learning and radiomics to improve breast tumor diagnosis. The model combines MobileNet with ResNeXt-inspired depthwise separable and grouped convolutions, enhancing feature processing and efficiency while reducing parameters. It was validated internally and externally using the AI-Dhabyani and TCIA breast ultrasound datasets and compared with VGG16, ResNet, AlexNet, and MobileNet.

Adjuvant chemotherapy benefits patients with resected pancreatic ductal adenocarcinoma (PDAC), but the compromised physical state of post-operative patients can hinder compliance. Biomarkers that identify candidates for prompt adjuvant therapy are needed. In this prospective observational study, 1,171 patients with PDAC who underwent pancreatectomy were enrolled and extensively followed-up. Proteomic profiling of 191 patient samples unveiled clinically relevant functional protein modules. A proteomics-level prognostic risk model was established for PDAC, with its utility further validated using a publicly available external cohort. More importantly, through an interaction effect regression analysis leveraging both clinical and proteomic datasets, we discovered two biomarkers (NDUFB8 and CEMIP2), indicative of the overall sensitivity of patients with PDAC to adjuvant chemotherapy. The biomarkers were validated through immunohistochemistry on an internal cohort of 386 patients. Rigorous validation extended to two external multicentic cohorts-a French multicentric cohort (230 patients) and a cohort from two grade-A tertiary hospitals in China (466 patients)-enhancing the robustness and generalizability of our findings. Moreover, experimental validation through functional assays was conducted on PDAC cell lines and patient-derived organoids. In summary, our cohort-scale integration of clinical and proteomic data demonstrates the potential of proteomics-guided prognosis and biomarker-aided adjuvant chemotherapy for PDAC.

Adverse events of atrial fibrillation (AF) have been commonly reported in lymphoma patients in treating Bruton's tyrosine kinase inhibitors (BTKi). The incidence rate of AF can vary depending on the specific types of BTKi and the patient population. Totally 45 published studies have revealed that the overall incidence rate of AF is 5% (95% CI 4%–7%). By performing a subtype single-rate analysis, the second-generation BTKi shows a lower AF incidence rate and lower cardiovascular toxicity. In the subtype single-rate analysis, we conclude the different AF incidence rates of Ibrutinib (10%, 95% CI 7%–13%), Acalabrutinib (4%, 95% CI 1%–6%), Orelabrutinib (0%, 95% CI 0%–1%), and Zanubrutinib (0%, 95% CI 0%–1%). The comprehensive analysis of AF inspires us to better predict and manage AF and other cardiovascular events in treating lymphoma. Meticulous evaluation, collaboration between cardiologists and hematologists, and discovery of new biomarkers are essential for its management.

To compare performance of whole-body [68Ga]Ga-FAPI-04 and [18F]FDG PET imaging in the detection of Krukenberg tumors (KTs), primary site and extra-ovarian metastases of gastric signet-ring-cell carcinoma (GSRCC), and evaluate the value of [68Ga]Ga-FAPI-04 PET/MR imaging strategy and its potential impact on the management of KTs from GSRCC. Twelve patients with twenty-three KTs from GSRCC, who underwent both [68Ga]Ga-FAPI-04 pelvic PET/MR and whole-body [68Ga]Ga-FAPI-04 and [18F]FDG PET imaging were retrospectively analyzed. [68Ga]Ga-FAPI-04 and [18F]FDG uptakes were compared by using Wilcoxon signed-rank test or paired t test. McNemar’s test was used to compare lesion detectability between two modalities. Two-tailed P<0.05 was considered statistically significant. Immunohistochemistry staining was utilized to analyze the fibroblast activation protein (FAP) expression in KTs. A total of 12 patients with 23 KTs from GSRCC (8 synchronous and 4 metachronous) were evaluated. [68Ga]Ga-FAPI-04 was superior to [18F]FDG PET in detecting primary sites of GSRCC (100

The existing body of research underscores the critical impact of intratumoral microbiomes on the progression of pancreatic ductal adenocarcinoma (PDAC), particularly in reshaping the tumor microenvironment and influencing gemcitabine resistance. However, peritumoral tissues’ microbiome, distinct from PDAC tumors, remain understudied, and Western-centric analyses overlooking potential variations in dietary-influenced microbiomes. Our study addresses this gap by 16S rRNA sequencing of PDAC tumors and matched peritumoral tissues from Chinese Mainland patients. Our research has uncovered that the microbiome composition within tumors and paired peritumoral tissues exhibits a high degree of similarity, albeit with certain discrepancies. Notably, Exiguobacterium is found to be more abundant within the tumor tissues. Further investigations have revealed that a lower Exiguobacterium/Bacillus ratio in both the tumor and peritumoral tissues of PDAC patients is indicative of a more favorable prognosis. Further exploration utilizing an orthotopic tumor model demonstrates that the probiotic Bacillus Coagulans impedes PDAC progression, accompanied by an increased infiltration of inflammatory neutrophils in tumors. Additionally, in the subgroup with a low Exiguobacterium/Bacillus ratio, whole-exome sequencing reveals elevated missense mutations in ABL2 and MSH2. The elevated expression of ABL2 and MSH2 has been correlated with poorer prognostic outcomes in PDAC patients. Together, these insights shed light on risk factors influencing PDAC progression and unveil potential therapeutic targets, alongside probiotic intervention strategies.

OBJECTIVES:The TP53 mutation, a prevalent tumor suppressor gene alteration, is linked to chemotherapy resistance, increased relapse rates and diminished overall survival (OS) in acute myeloid leukemia (AML) patients. METHODS:In this study, we characterize the TP53 mutation phenotypes across various AML cohorts utilizing The Cancer Genome Atlas (TCGA) data. We devised a TP53-related prognostic signature derived from differentially expressed genes between mutated and wild-type TP53 AML specimens. In-depth analyses were conducted, encompassing genetic variation, immune cell infiltration and prognostic stratification. RESULTS:A six-gene TP53-related signature was established using least absolute shrinkage and selection operator (LASSO)-Cox regression, demonstrating robust prognostic predictability. This signature exhibited strong performance in both the OHSU validation cohorts, an independent Gene Expression Omnibus (GEO) validation cohort (GSE71014) and proved by results of the in vivo experiment. Finally, we used single cell database (GSE198681) to observe the characteristics of these six genes. DISCUSSION:Our study may facilitate the development of efficacious therapeutic approaches and provide a novel idea for future research. Conclusion: The TP53-related signature and pattern hold the potential to refine prognostic stratification and underscore emerging targeted therapies.

OBJECTS:To evaluate the prognostic value of radiomics features extracted from 18F-FDG-PET/CT images and integrated with clinical characteristics and conventional PET/CT metrics in newly diagnosed multiple myeloma (NDMM) patients. METHODS:We retrospectively reviewed baseline clinical information and 18F-FDG-PET/CT imaging data of MM patients with 18F-FDG-PET/CT. Multivariate Cox regression models involving different combinations were constructed, and stepwise regression was performed: (1) radiomics features of PET/CT alone (Rad Model); (2) Using clinical data (including clinical/laboratory parameters and conventional PET/CT metrics) only (Cli Model); (3) Combination radiomics features and clinical data (Cli-Rad Model). Model performance was evaluated by C-index and Net Reclassification Index (NRI). RESULTS:Ninety-eight patients with NDMM who underwent 18F-FDG-PET/CT between 2014 and 2019 were included in this study. Combining radiomics features from PET/CT with clinical data showed higher prognostic performance than models with radiomics features or clinical data alone (C-index 0.790 vs. 0.675 vs. 0.736 in training cohort; 0.698 vs. 0.651 vs. 0.563 in validation cohort; AUC 0.761, sensitivity 56.7%, specificity 85.7%, p < 0.05 in training cohort and AUC 0.650, sensitivity 80.0%, specificity78.6%, p < 0.05 in validation cohort) When clinical data was combined with radiomics, an increase in the performance of the model was observed (NRI > 0). CONCLUSIONS:Radiomics features extracted from the PET and CT components of baseline 18F-FDG-PET/CT images may become an effective complement to provide prognostic information; therefore, radiomics features combined with clinical characteristic may provide clinical value for MM prognosis prediction.

Background LIPH, a membrane-associated phosphatidic acid-selective phospholipase A1a, can produce LPA (Lysophosphatidic acid) from PA (Phosphatidic acid) on the outer leaflet of the plasma membrane. It is well known that LIPH dysfunction contributes to lipid metabolism disorder. Previous study shows that LIPH was found to be a potential gene related to poor prognosis with pancreatic ductal adenocarcinoma (PDAC). However, the biological functions of LIPH in PDAC remain unclear. Methods Cell viability assays were used to evaluate whether LIPH affected cell proliferation. RNA sequencing and immunoprecipitation showed that LIPH participates in tumor glycolysis by stimulating LPA/LPAR axis and maintaining aldolase A (ALDOA) stability in the cytosol. Subcutaneous, orthotopic xenograft models and patient-derived xenograft PDAC model were used to evaluate a newly developed Gemcitabine-based therapy. Results LIPH was significantly upregulated in PDAC and was related to later pathological stage and poor prognosis. LIPH downregulation in PDAC cells inhibited colony formation and proliferation. Mechanistically, LIPH triggered PI3K/AKT/HIF1A signaling via LPA/LPAR axis. LIPH also promoted glycolysis and de novo synthesis of glycerolipids by maintaining ALDOA stability in the cytosol. Xenograft models show that PDAC with high LIPH expression levels was sensitive to gemcitabine/ki16425/aldometanib therapy without causing discernible side effects. Conclusion LIPH directly bridges PDAC cells and tumor microenvironment to facilitate aberrant aerobic glycolysis via activating LPA/LPAR axis and maintaining ALDOA stability, which provides an actionable gemcitabine-based combination therapy with limited side effects. Graphical Abstract

BackgroundLipomatous atrial septal hypertrophy (LASH) with atrial septal defect (ASD) is a rare congenital anomaly. Although LASH is a histologically benign cardiac lesion characterized by excessive fat deposition in the interatrial septum that spares the fossa ovale, it has been associated with supraventricular arrhythmias or sick sinus syndrome. Application of multimodal imaging is crucial for accurate diagnosis, appropriate treatment of LASH with ASD, and follow-up.Case summaryA 68-year-old female patient presented with recurrent chest tightness and palpitation. Multimodal imaging revealed the characterizations of LASH and ASD. Two-dimensional transesophageal echocardiography showed a “dumbbell”-shaped involvement of the cephalad and caudal regions with sparing of a single secundum ASD. The septum with a brightness feature is an uncommon condition characterized by the deposition of unencapsulated fat cells in the atrial septum. Real-time four-dimensional transesophageal echocardiography reflected the lipomatous hypertrophy of the atrial septum and an oval-shaped ASD. Cardiac computer tomography angiography later confirmed this finding. The patient achieved a good clinical response with an ASD percutaneous occlusion guided by intracardiac echocardiography (ICE).ConclusionThis case demonstrates a LASH combined with ASD. Multimodality imaging can provide an accurate diagnosis and may guide the procedure for precise occlusion.

Objectives:This study aims to evaluate the diagnostic value of real-time four-dimensional transesophageal echocardiography (RT4D-TEE) for implant-related thrombus (IRT).Methods:We collected 1,125 patients with atrial fibrillation from May 2019 to February 2022 in our hospital. All patients accepted transesophageal echocardiography (TEE) examination to exclude any thrombi before the LAAC procedure.Results:There were 760 patients with LAAC, 66 patients with CIED, and 299 patients without any implantations. A total of 40 patients with an established diagnosis of IRT were further analyzed. The accurate detection rate of IRT by RT4D-TEE was 4.8% (40/826), which was higher than 3.8% (31/826) by 2D-TEE (P = 0.004). No IRT was found on TEE in the rest of the 786 patients. These 40 patients were divided into LAAC (n = 23) and CIED (n = 17) groups according to the results of RT4D-TEE. In the LAAC group, IRT distributed on different parts of the LAA occluder surface, 91.3% (21/23) with clumps of thrombi, and 8.7% (2/23) with a thin layer of thrombi covering the surface of the occluder. In the CIED group, thrombi were seen attached to the leads in the right atrium and right ventricle. The thrombi were beaded in 17.6% (3/17), corded in 17.6% (3/17), and clotted in the remaining 64.7% (11/17) of cases. After adjusting the anticoagulant dosage and following up for 6 months, 20% (8/40) of cases were successfully resolved, 67.5% (27/40) became smaller, and 12.5% (5/40) showed no changes.Conclusion:The accurate detection rate of IRT by RT4D-TEE was significantly higher than that by 2D-TEE. 2D-TEE has limitations, but RT4D-TEE can be used as an effective complementary method. Imaging and some clinical features differ significantly between IRT on occluder and IRT on CIED lead.

Neuropathy is a feature more frequently observed in pancreatic ductal adenocarcinoma (PDAC) than other tumors. Schwann cells, the most prevalent cell type in peripheral nerves, migrate toward tumor cells and associate with poor prognosis in PDAC. To unveil the effects of Schwann cells on the neuro-stroma niche, here we perform single-cell RNA-sequencing and microarray-based spatial transcriptome analysis of PDAC tissues. Results suggest that Schwann cells may drive tumor cells and cancer-associated fibroblasts (CAFs) to more malignant subtypes: basal-like and inflammatory CAFs (iCAFs), respectively. Moreover, in vitro and in vivo assays demonstrate that Schwann cells enhance the proliferation and migration of PDAC cells via Midkine signaling and promote the switch of CAFs to iCAFs via interleukin-1α. Culture of tumor cells and CAFs with Schwann cells conditioned medium accelerates PDAC progression. Thus, we reveal that Schwann cells induce malignant subtypes of tumor cells and CAFs in the PDAC milieu.

Background: Diffuse large B-cell lymphoma (DLBCL) patients with extranodal involvement and double expression of MYC and BCL2 often have a poorer prognosis when treated with the standard first-line R-CHOP regimen. The 5-year progression-free survival (PFS) and overall survival (OS) rates are both below 40% for these high-risk DLBCL cases. In this study, we perform a retrospective analysis of the clinical outcomes and adverse events of the high-risk DLBCL patients with extranodal involvement and double expression, who were admitted to our center and used Bruton's tyrosine kinase inhibitor (BTKi) zanubrutinib on the basis of R-CHOP regimen. Methods: We conducted a retrospective analysis of 26 DLBCL patients with extranodal involvement or MYC/BCL2 double expression who were admitted to our center and used R-CHOP regimen in combination with zanubrutinib between 1 st January 2021 and 30 th April 2023 (Figure A). Of these patients, 19 had extranodal involvement, and 7 were identified as double expression cases. The patients had a median age of 70 years, ranging from 34 to 87. Among them, 20 cases (77%) were aged over 60, and 8 cases (30%) were aged over 75. Moreover, 20 cases (76.9%) exhibited an Eastern Cooperative Oncology Group (ECOG) performance status score higher than 2 points. All the patients received an induction regimen consisting of zanubrutinib in combination with R-CHOP for a total of 4 cycles. After the fourth cycle, treatment efficacy was assessed using 18FDG-PET/CT scans. Patients achieving partial response (PR) or better continued with rituximab in combination with zanubrutinib for consolidation maintenance therapy, lasting for 1 year. For patients at risk of central nervous system involvement, oral administration of zanubrutinib continued for 2 years. During the treatment period, imaging evaluations were performed every 3 months to assess treatment response (Figure B). Results: After the induction therapy, a mid-term PET/CT evaluation showed that all patients achieved PR or above, resulting in an overall response rate (ORR) of 100%. Among them, 19 patients (73.1%) achieved complete response (CR), while 7 patients (26.9%) achieved PR. During the consolidation and maintenance therapy, 7 patients who were initially in PR converted to CR. As of the latest follow-up, with a median follow-up duration of 11 months (ranging from 4.1 to 30.0 months), 2 patients (7.7%) were lost to follow-up, and 2 patients (7.7%) experienced disease progression. The median PFS and OS were not reached. The 2-year PFS was 69.7±13.4% (Figure C), and the 2-year OS was 77.4±12.2% (Figure D). Non-hematological adverse events included fatigue (38.5%), hypertension (15.38%), neurological symptoms (7.7%), and infections (100%). Among the infections, 3 cases (11.5%) were of >3-grade and led to treatment discontinuation. Additionally, one patient experienced immune encephalitis and went into a coma. Hematological adverse events included granulocytopenia (55%), anemia (26%), thrombocytopenia (42.3%), and bleeding (38.5%). Among them, >3-grade granulocytopenia occurred in 4.5% of the patients. Five patients who were on long-term anticoagulant therapy due to concurrent cardiovascular diseases experienced a reduction in zanubrutinib dosage during the follow-up period, resulting in an improvement in bleeding symptoms. Conclusions: The combination of 4 cycles of R-CHOP regimen with zanubrutinib in the induction treatment of DLBCL patients with high-risk factors, such as extranodal involvement or MYC/BCL2 double expression, has shown promising clinical outcomes especially in older or unfit/frail patients. This approach allows for a reduction in the number of cytotoxic drug cycles, thereby improving the patients' tolerance to the treatment. Moreover, the efficacy of this regimen is superior to the traditional 6-8 cycles of R-CHOP induction therapy. Furthermore, the consolidation and maintenance therapy with rituximab in combination with zanubrutinib has demonstrated good safety and manageable adverse effects. This approach exhibits hope for further enhancing the prognosis of high-risk DLBCL patients.

HomeCirculation: Cardiovascular ImagingVol. 16, No. 5Multimodality Imaging in Diagnosing Left Atrial Appendage Atresia of the Ostium No AccessCase ReportRequest AccessFull TextAboutView Full TextView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissionsDownload Articles + Supplements ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toSupplemental MaterialNo AccessCase ReportRequest AccessFull TextMultimodality Imaging in Diagnosing Left Atrial Appendage Atresia of the Ostium Yi Yu, Ming Ding, Yu-Han Chen, Ting Wang, Xiao-Li Tang, Xiao-Hong Huang, Ling-Wei Yu, Yue-Peng Wang and Yi-Gang Li Yi YuYi Yu https://orcid.org/0000-0002-6286-4985 Department of Cardiology (Y.Y., Y.-H.C., T.W., X.-L.T., X.-H.H., Y.-P.W., Y.-G.L.), Xinhua Hospital affiliated to School of Medicine, Shanghai JiaoTong University, China. , Ming DingMing Ding Department of Radiology (M.D., L.-W.Y.), Xinhua Hospital affiliated to School of Medicine, Shanghai JiaoTong University, China. , Yu-Han ChenYu-Han Chen Department of Cardiology (Y.Y., Y.-H.C., T.W., X.-L.T., X.-H.H., Y.-P.W., Y.-G.L.), Xinhua Hospital affiliated to School of Medicine, Shanghai JiaoTong University, China. , Ting WangTing Wang Department of Cardiology (Y.Y., Y.-H.C., T.W., X.-L.T., X.-H.H., Y.-P.W., Y.-G.L.), Xinhua Hospital affiliated to School of Medicine, Shanghai JiaoTong University, China. , Xiao-Li TangXiao-Li Tang Department of Cardiology (Y.Y., Y.-H.C., T.W., X.-L.T., X.-H.H., Y.-P.W., Y.-G.L.), Xinhua Hospital affiliated to School of Medicine, Shanghai JiaoTong University, China. , Xiao-Hong HuangXiao-Hong Huang Department of Cardiology (Y.Y., Y.-H.C., T.W., X.-L.T., X.-H.H., Y.-P.W., Y.-G.L.), Xinhua Hospital affiliated to School of Medicine, Shanghai JiaoTong University, China. , Ling-Wei YuLing-Wei Yu Department of Radiology (M.D., L.-W.Y.), Xinhua Hospital affiliated to School of Medicine, Shanghai JiaoTong University, China. , Yue-Peng WangYue-Peng Wang Department of Cardiology (Y.Y., Y.-H.C., T.W., X.-L.T., X.-H.H., Y.-P.W., Y.-G.L.), Xinhua Hospital affiliated to School of Medicine, Shanghai JiaoTong University, China. and Yi-Gang LiYi-Gang Li https://orcid.org/0000-0003-3007-7212 Department of Cardiology (Y.Y., Y.-H.C., T.W., X.-L.T., X.-H.H., Y.-P.W., Y.-G.L.), Xinhua Hospital affiliated to School of Medicine, Shanghai JiaoTong University, China. Originally published30 Jan 2023https://doi.org/10.1161/CIRCIMAGING.122.014858Circulation: Cardiovascular Imaging. 2023;16Footnotes*Drs Yu and Ding contributed equally.For Sources of Funding and Disclosures, see page 444Supplemental Material is available at https://www.ahajournals.org/doi/suppl/10.1161/CIRCIMAGING.122.014858.Correspondence to: Yi Yu, MD or Yi-Gang Li, MD, Department of Cardiology, Xinhua Hospital affiliated to School of Medicine, Shanghai JiaoTong University, 1665 Kongjiang Road, Shanghai, 200092, PR China. Email liyigang@xinhuamed.com.cnCorrespondence to: Yi-Gang Li, MD, Department of Cardiology, Xinhua Hospital affiliated to School of Medicine, Shanghai JiaoTong University, 1665 Kongjiang Road, Shanghai, 200092, PR China. Email liyigang@xinhuamed.com.cnReferences1. Sakatani Y, Ito T, Hasegawa H, Akamatsu K, Hoshiga M. Left atrial appendage ostial stenosis: a case report and literature review.Am J Case Rep. 2021; 22:e930510. doi: 10.12659/AJCR.930510CrossrefMedlineGoogle Scholar2. Cresti A, Solari M, Gismondi AL, Baratta P, Sensi FD, Breschi M, Limbruno U. Incidence and clinical relevance of left atrial appendage membranes: a new congenital heart disease?Eur Heart J Cardiovasc Imaging. 2022; 23:673–679. doi: 10.1093/ehjci/jeab076CrossrefMedlineGoogle Scholar3. Collier P, Cavalcante JL, Phelan D, Thavendiranathan P, Dahiya A, Grant A, Kwon D, Thamilarasan M. Congenital absence of the left atrial appendage.Circ Cardiovasc Imaging. 2012; 5:549–550. doi: 10.1161/CIRCIMAGING.112.975516LinkGoogle Scholar4. Pashuna RA, Gannonb MP, Tomassettic C, Rahmanid N, Sabaa SG. Congenital absence of the left atrial appendage.J Cardiovasc Comput Tomogr. 2020; 14:e115–e117. doi: 10.1016/j.jcct.2019.07.009CrossrefMedlineGoogle Scholar Previous Back to top Next FiguresReferencesRelatedDetails May 2023Vol 16, Issue 5 Advertisement Article InformationMetrics © 2023 American Heart Association, Inc.https://doi.org/10.1161/CIRCIMAGING.122.014858PMID: 36715026 Originally publishedJanuary 30, 2023 Keywordsatresia of the ostiumleft atrial appendagemultimodality imagingPDF download Advertisement SubjectsComputerized Tomography (CT)EchocardiographyImaging