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To determine the factors contributing to successful mitral valve repair (MVP) and to discuss the effect of complex techniques on the durability of MVP for active infective endocarditis (IE) affecting the mitral valve.One hundred and eighty-seven patients were enrolled; 39.6% underwent mitral valve replacement (MVR) and 60.4% underwent MVP. We used logistic regression to identify influencing factors of the choice of surgical technique. The results were compared between groups and subgroups after propensity score matching (PSM).Risk factors for MVR included poor valve quality (odds ratio [OR] 23.3, p = .001), a large defect after debridement (OR 16.4, p .001), and heavy valve infection (OR 3.7, p = .027). After PSM, we did not find a significant difference in the frequency of major postoperative complications or the in-hospital or postdischarge death rate. The reintervention rate for MVP was significantly higher than that for MVR (p = .047). Subgroup analysis found a significant relationship between the use of a complex repair technique and the need for reoperation (p = .020).The choice of valve repair or replacement for patients with active IE affecting the mitral valve was influenced by the intraoperative characteristics of the infected valve rather than the severity of systemic infection or overall health status. The choice of surgical treatment strategy had no effect on major postoperative complications, in-hospital mortality, or medium-term survival. However, the medium-term durability of MVP was poorer than that of MVR. The use of the patch technique for free margins or extensive leaflet defects was associated with a need for reintervention.

The aggravation risk of malignancies related gastrointestinal bleeding (M-GIB) after cardiac surgery under cardiopulmonary bypass (CPB) was unknown, our study aimed to demonstrate the risk to help clinical decision making under this complicated circumstance. 19 patients with preoperative M-GIB and underwent cardiac surgery with CPB constituted the exposed group. Up to 5 controls were matched for each exposed patient according to age, sex and surgery type and constituted the control group. We defined a seven-grade ordinal scale to assess the clinical severity of gastrointestinal bleeding (GIB). Pre-and post-operative GIB grade and other clinical endpoints were compared between the two groups. Among our cardiac surgery patients, M-GIB were caused mostly by TNM grade III gastrointestinal cancer. Antiplatelet drugs or anticoagulants were reduced preoperatively for 47.4% patients and postoperatively for 42.1% patients considering the risk of GIB. Although postoperative GIB grade was higher (P = 0.042) compared to the controls, we found no postoperative aggravation of GIB in the exposed group. After cardiac surgery, 89.5% patients underwent gastrointestinal surgery as scheduled. Although the priority of cardiac or gastrointestinal surgery for patients with cardiac surgical indication and M-GIB was difficult to decide, cardiac surgery didn’t increase the aggravation risk of M-GIB.

A 47-year-old previously healthy man was referred to a local hospital with chest tightness, oliguria, and lower extremity edema for seven days. An initial investigation revealed acute heart failure and kidney injury. The patient was intensively treated with cardiac and renal replacement therapy, and cardiorenal function improved one week later. Two months later, echocardiography was performed because chest tightness and edema had not resolved. Echocardiography showed Valsalva sinus rupture, and the patient was transferred to our center. Myocardial calcification was observed in the left ventricular wall on computed tomography after admission. The patient underwent cardiac surgery and recovered smoothly. At the three-year follow up, the patient was asymptomatic with normal renal function and serum electrolytes. Imaging revealed a significant reduction in diffuse calcification of the left ventricular wall. This case indicates that this rare form of reversible myocardial calcification may be associated with acute heart and renal failure caused by Valsalva sinus rupture. The results of this case will guide clinicians about further management and timely referral of such patients to appropriate specialties.

In autoimmune hepatitis (AIH), the persisting inflammation contributes to fibrosis progression, for which conventional biochemical markers manifest relatively unsatisfactory prediction. Herein, we assessed the value of serum CD48 (sCD48) as an indicator for inflammation and fibrosis in AIH type 1. The levels of sCD48 were detected first in an exploratory cohort using ELISA. In this cohort, compared with healthy controls (4.90 ng/mL, P 0.0001), primary biliary cholangitis (7.32 ng/mL, P 0.0001), and non-alcoholic fatty liver disease (7.76 ng/mL, P 0.0001), sCD48 levels were elevated in AIH (12.81 ng/mL) and correlated with histological inflammation and fibrosis. Further using multivariate logistic regression analysis, sCD48 was identified as an independent predictor for both significant inflammation (G3-4) and advanced fibrosis (S3-4). Two predictive scores, based on sCD48, were constructed for diagnosing significant inflammation and advanced fibrosis (sCD48-AIH-SI and sCD48-AIH-AF, respectively). Using these data as a premise, predictive abilities were subsequently evaluated and verified in a validation cohort. In the exploratory cohort, the area under the receiver operating characteristic curve of sCD48 and sCD48-AIH-SI, for significant inflammation, were 0.748 and 0.813, respectively. Besides, during treatment follow-up, sCD48 levels gradually decreased from immunosuppression initiation to re-evaluation biopsy, in parallel with aspartate transaminase, total sera IgG, and fibrosis-4 score. For AIH patients in a re-evaluation biopsy cohort, sCD48 could predict significant fibrosis (S2-4). Further using immunohistochemistry, hepatic CD48 expression was elevated in AIH patients and decreased after treatment. In conclusion, sCD48 and sCD48-based predictive scores predict histological inflammation and fibrosis in AIH-1. Detecting sCD48 might help in the clinical management of AIH.

The role of congenital thrombophilia in chronic thromboembolic pulmonary hypertension (CTEPH) remains unresolved.The purpose of this study was to investigate the prevalence, genetic background, and clinical phenotype of congenital thrombophilia in CTEPH.In total, 367 patients with CTEPH from May 2013 to December 2020 were consecutively enrolled in this cross-sectional study in FuWai Hospital and Peking Union Medical College Hospital in China. The primary outcome was the occurrence of congenital thrombophilia diagnosed through tests for congenital anticoagulants activity (including protein C, protein S, and antithrombin III), factor V Leiden and prothrombin G20210A sequence variants. Next-generation sequencing was conducted for patients with congenital thrombophilia. Clinical phenotype was compared between patients with and without thrombophilia.A total of 36 (9.8%; 95% CI: 6.8%-12.9%) patients were diagnosed as congenital thrombophilia, including 13 protein C deficiency (3.5%; 95% CI: 1.6%-5.4%), 19 protein S deficiency (5.2%; 95% CI: 2.9%-7.5%), and 4 antithrombin III deficiency (1.1%; 95% CI: 0%-2.2%). No factor V Leiden or prothrombin G20210A sequence variants were identified. Genotype for patients with thrombophilia revealed that 10 (76.9%) protein C deficiency patients were PROC sequence variant carriers, 4 (21.1%) protein S deficiency were PROS1 sequence variant carriers, and 2 (50.0%) antithrombin III deficiency were SERPINC1 sequence variant carriers. In the logistic regression model, male sex (OR: 3.24; 95% CI: 1.43-7.31) and proximal lesion in pulmonary arteries (OR: 4.10; 95% CI: 1.91-8.85) had significant differences between the congenital thrombophilia and nonthrombophilia group in CTEPH patients.Congenital thrombophilia was not rare. Male sex and proximal lesion in pulmonary arteries might be the specific clinical phenotype for CTEPH patients with congenital thrombophilia.

To identify which patient with prostate cancer (PCa) could safely avoid extended pelvic lymph node dissection (ePLND) by predicting lymph node invasion (LNI), via a radiomics-based machine learning approach.An integrative radiomics model (IRM) was proposed to predict LNI, confirmed by the histopathologic examination, integrating radiomics features, extracted from prostatic index lesion regions on MRI images, and clinical features via SVM. The study cohort comprised 244 PCa patients with MRI and followed by radical prostatectomy (RP) and ePLND within 6 months between 2010 and 2019. The proposed IRM was trained in training/validation set and evaluated in an internal independent testing set. The model's performance was measured by area under the curve (AUC), sensitivity, specificity, negative predictive value (NPV), and positive predictive value (PPV). AUCs were compared via Delong test with 95% confidence interval (CI), and the rest measurements were compared via chi-squared test or Fisher's exact test.Overall, 17 (10.6%) and 14 (16.7%) patients with LNI were included in training/validation set and testing set, respectively. Shape and first-order radiomics features showed usefulness in building the IRM. The proposed IRM achieved an AUC of 0.915 (95% CI: 0.846-0.984) in the testing set, superior to pre-existing nomograms whose AUCs were from 0.698 to 0.724 (p0.05).The proposed IRM could be potentially feasible to predict the risk of having LNI for patients with PCa. With the improved predictability, it could be utilized to assess which patients with PCa could safely avoid ePLND, thus reduce the number of unnecessary ePLND.• The combination of MRI-based radiomics features with clinical information improved the prediction of lymph node invasion, compared with the model using only radiomics features or clinical features. • With improved prediction performance on predicting lymph node invasion, the number of extended pelvic lymph node dissection (ePLND) could be reduced by the proposed integrative radiomics model (IRM), compared with the existing nomograms.

In the present study, we analyzed the advantages and feasibility of non-open-heart surgery without cardiopulmonary bypass for intracardiac intravenous leiomyomatosis.We retrospectively reviewed 23 cases of intracardiac intravenous leiomyomatosis and divided them into a noncardiopulmonary bypass (NCPB) group (9 cases) and a cardiopulmonary bypass (CPB) group (14 cases) according to the surgical treatment received. The clinical characteristics and anatomic features, including the diameter of the tumor, right atrium, and inferior vena cava, were recorded, and the perioperative data, including the operation time, blood loss, postoperative hemoglobin change, and follow-up results, were analyzed and compared between the two groups.The NCPB group had required a shorter operation time (321.9 ± 104.2 minutes vs 526.3 ± 95.6 minutes; P .001) and had experienced less blood loss (456.3 ± 249.9 mL vs 815.4 ± 435.6 mL; P = .048) compared with the CPB group. The NCPB group had a small maximum cross-sectional area of the tumor inside the right atrium (475.5 ± 509.6 mmFor intravenous leiomyomatosis with a smaller cross-sectional area in the right atrium that can be mobilized, surgery without CBP is feasible and should be considered.

Neurocognitive impairment is a core feature of schizophrenia, and patients with first-episode schizophrenia (FES) are optimal candidates for cognitive remediation, but we do not know enough about the incidence, severity and longitudinal changes in neurocognitive impairment in those with FES. This study aimed to assess the neurocognitive trajectories of patients with FES and to compare the clinical and functional outcomes among those with different trajectories. A total of 562 untreated patients with FES completed a neurocognitive test battery and psychopathological and functional assessment. A total of 373 patients attended the follow-up. Group-based trajectory modelling (GBTM) was applied to identify neurocognitive trajectories. Analysis of variance and chi-square tests were conducted to compare demographic characteristics, multiple neurocognitive domains, and clinical and functional outcomes among the different subgroups. We identified three neurocognitive subgroups: preserved (n = 133), mildly to moderately impaired (n = 187) and severely impaired (n = 53). Neurocognitive function in the two impaired subgroups improved within a year but failed to reach the normal level. The processing speed followed trajectories similar to those of overall cognition. The three subgroups did not significantly differ in antipsychotic usage or clinical remission rate. The severely impaired subgroup had poorer functional outcomes than the preserved subgroup, but the mildly to moderately impaired subgroup did not. Patients with FES followed distinct neurocognitive trajectories during the first year of treatment. Patients with severe neurocognitive impairment have poorer functional outcomes, which require and are more likely to benefit from cognitive remediation. Processing speeding is a potential indicator for screening overall cognition.

The coronavirus disease 2019 (COVID-19) pandemic has been and will continue to be a challenge to the healthcare system worldwide. In this context, we aimed to discuss the impact of the COVID-19 pandemic on the diagnosis, timing, and prognosis of surgical treatment for active infective endocarditis (IE) during the pandemic and share our coping strategy.A total of 39 patients were admitted for active IE in the year 2020. The number of the same period last year was 50. Medical information of these two groups was extracted from our surgical database. Data were compared between the two groups and differences with or without statistical significance were discussed.In the pandemic year, we admitted fewer transferred patients (64.1% vs. 80%, p = .094). Timespan for diagnosis were prolonged (60 vs. 34.5 days, p = .081). More patients were admitted in emergency (41% vs. 20%, p = .030) More patients had heart failure (74.4% vs. 40%, p = .001), sepsis (69.2% vs. 42.0%, p = .018), or cardiogenic shock (25.6% vs. 8.0%, p = .038). Overall surgical risk (EuroSCORE II) was higher (4.15% vs. 3.24%, p = .019) and more commando surgery was performed (7.7% vs. 2.0%, p = .441). However, we did not see more postoperative complications, and early mortality was not worse either (0 vs. 4%, p = .502).The negative impact of the COVID-19 pandemic on the clinical practice of surgical treatment for active IE was multifaceted. However, with the preservation of the effectiveness of multidisciplinary IE surgical team, the early outcomes were comparable with those in the normal years.

This study aimed to investigate the common status of self-management in liver transplant recipients and to explore the mediating role of hope in the relationship between social support and self-management. Two hundred and ten liver transplant recipients from two tertiary hospitals were included. Questionnaires were used for general demographic information, the Perceived Social Support Scale, the Herth Hope Index, and the Self-Management Questionnaire for Liver Transplantation Recipients. Lifestyle management of liver transplant recipients was good, while the communication with physicians, cognitive symptom management, and exercise dimensions were less than satisfactory. Minimal assurance of family and education levels were significantly associated with self-management. Social support was positively correlated with self-management and hope ( r = .31, p

Immune checkpoint therapy (ICT) using antibody blockade of programmed cell death protein 1 (PD-1) or cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) can provoke T cell–dependent antitumor activity that generates durable clinical responses in some patients. The epigenetic and transcriptional features that T cells require for efficacious ICT remain to be fully elucidated. Herein, we report that anti–PD-1 and anti–CTLA-4 ICT induce upregulation of the transcription factor BHLHE40 in tumor antigen–specific CD8+ and CD4+ T cells and that T cells require BHLHE40 for effective ICT in mice bearing immune-edited tumors. Single-cell RNA sequencing of intratumoral immune cells in BHLHE40-deficient mice revealed differential ICT-induced immune cell remodeling. The BHLHE40-dependent gene expression changes indicated dysregulated metabolism, NF-κB signaling, and IFNγ response within certain subpopulations of CD4+ and CD8+ T cells. Intratumoral CD4+ and CD8+ T cells from BHLHE40-deficient mice exhibited higher expression of the inhibitory receptor gene Tigit and displayed alterations in expression of genes encoding chemokines/chemokine receptors and granzyme family members. Mice lacking BHLHE40 had reduced ICT-driven IFNγ production by CD4+ and CD8+ T cells and defects in ICT-induced remodeling of macrophages from a CX3CR1+CD206+ subpopulation to an iNOS+ subpopulation that is typically observed during effective ICT. Although both anti–PD-1 and anti–CTLA-4 ICT in BHLHE40-deficient mice led to the same outcome—tumor outgrowth—several BHLHE40-dependent alterations were specific to the ICT that was used. Our results reveal a crucial role for BHLHE40 in effective ICT and suggest that BHLHE40 may be a predictive or prognostic biomarker for ICT efficacy and a potential therapeutic target.

Supplementary Figure from BHLHE40 Regulates the T-Cell Effector Function Required for Tumor Microenvironment Remodeling and Immune Checkpoint Therapy Efficacy

Supplementary Table S1

Supplementary Fig. S3. Differentiation of ML NK cells and Preactivated-Expanded CB-NK cells.

Supplementary Materials and Methods

Purpose:Natural killer (NK)-cell recognition and function against NK-resistant cancers remain substantial barriers to the broad application of NK-cell immunotherapy. Potential solutions include bispecific engagers that target NK-cell activity via an NK-activating receptor when simultaneously targeting a tumor-specific antigen, as well as enhancing functionality using IL12/15/18 cytokine pre-activation.Experimental Design:We assessed single-cell NK-cell responses stimulated by the tetravalent bispecific antibody AFM13 that binds CD30 on leukemia/lymphoma targets and CD16A on various types of NK cells using mass cytometry and cytotoxicity assays. The combination of AFM13 and IL12/15/18 pre-activation of blood and cord blood–derived NK cells was investigated in vitro and in vivo.Results:We found heterogeneity within AFM13-directed conventional blood NK cell (cNK) responses, as well as consistent AFM13-directed polyfunctional activation of mature NK cells across donors. NK-cell source also impacted the AFM13 response, with cNK cells from healthy donors exhibiting superior responses to those from patients with Hodgkin lymphoma. IL12/15/18-induced memory-like NK cells from peripheral blood exhibited enhanced killing of CD30+ lymphoma targets directed by AFM13, compared with cNK cells. Cord-blood NK cells preactivated with IL12/15/18 and ex vivo expanded with K562-based feeders also exhibited enhanced killing with AFM13 stimulation via upregulation of signaling pathways related to NK-cell effector function. AFM13–NK complex cells exhibited enhanced responses to CD30+ lymphomas in vitro and in vivo.Conclusions:We identify AFM13 as a promising combination with cytokine-activated adult blood or cord-blood NK cells to treat CD30+ hematologic malignancies, warranting clinical trials with these novel combinations.

Objective In this study, the hemopericardium volume and pathological characteristics associated with cardiac ruptures caused by blunt violence, AMI, aortic dissection and CPR have been analyzed. The findings might provide reference and data support for deciphering the cause of heart rupture in forensic pathology. Method Pericardial water-injection tests were conducted in 22 noncardiac death subjects. Other study groups included 9 cases of myocardial infarction, 20 cases of aortic dissection rupture, 11 cases of cardiac rupture caused by trauma and 4 cases of cardiac rupture by CPR. The volume of hemopericardium and the pathological features were analyzed for each group. Result The hemopericardium volume in myocardial infarction and dissecting aneurysm rupture were significantly higher than the pericardial injection test in noncardiac subjects (p-value 0.05). The volume of hemopericardium in CPR-induced cardiac rupture had no difference with non-cardiac rupture and it was significantly lower than the pericardial injection test (p-value