Platelet count in heart failure patients undergoing left ventricular assist device.

AIMS: Left ventricular assist device (LVAD) implantation, a therapy for end-stage heart failure, is associated with platelet (PLT) activation. This study aims to evaluate the prognostic impact of PLT count in patients with LVAD implantation. METHODS AND RESULTS: Data from the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) registry were investigated, and patients were divided into three groups according to tertiles. The dynamic change of PLT counts and its associations with long-term outcomes were analysed. The primary outcome was long-term mortality. A total of 19 517 patients who received the first continuous-flow LVAD were identified from the INTERMACS registry. The PLT count underwent a dynamic change towards normalization after LVAD implantation. Compared with intermediate, both high (hazard ratio [HR], 1.09, 95% confidence interval [CI]: 1.01 to 1.17, P = 0.033) and low (HR, 1.18, 95% CI: 1.10 to 1.27, P < 0.001) pre-implant PLT counts were associated with an increased risk of 2 year mortality. Compared with intermediate, a high post-implant PLT count was associated with an increased risk of 4 year mortality (HR, 1.38, 95% CI: 1.26 to 1.52, P < 0.001). Besides, both pre- and post-implant PLT counts exhibit a U-shaped association with the risk of mortality. CONCLUSIONS: LVAD implantation could improve the PLT count towards normalization. Abnormal pre-/post-implant PLT counts were independently associated with increased risks of long-term mortality.

The cross-sectional correlation between the oxidative balance score and cardiometabolic risk factors and its potential correlation with longitudinal mortality in patients with cardiometabolic risk factors.

BACKGROUND: This study analyzes the correlation between oxidative balance score (OBS), cardiometabolic risk factors (CMRFs), and mortality in individuals with CMRFs. METHODS: Data were chosen from the National Health and Nutrition Examination Survey. The survey-weighted multivariable logistic regression models were implemented to explore the relationship between OBS and the risk of CMRFs. Then, Cox proportional hazard models were employed to estimate the impact of OBS on mortality in individuals with CMRFs. RESULTS: Following multivariate adjustment, the subjects in the highest quartile exhibited a 46% reduction in the risk of CMRFs, a 33% reduction in the risk of diabetes, a 31% reduction in the risk of hypertension, and a 36% reduction in the risk of hyperlipidemia, compared with those in the lowest quartile. Furthermore, each 1-unit increase in OBS was remarkably negatively correlated with the prevalence of CMRFs, diabetes, hypertension, and hyperlipidemia. The correlation between OBS and CMFRs was found to be mediated by serum γ-glutamyltransferase (GGT) and white blood cells (WBC), and the mediation effect of GGT levels and WBC, accounting for 6.90% and 11.51%, respectively. Lastly, the multivariate Cox regression model revealed that elevated OBS, irrespective of whether it was treated as a categorical or continuous variable, exhibited a significant association with decreased mortality from all causes, cardiovascular disease, and cancer. CONCLUSIONS: An increased OBS might reflect a lower risk of CMRFs and a favorable prognosis for individuals with CMRFs. Moreover, WBC and GGT may play a potential mediating role between OBS and CMRFs.

Identification of hub genes in calcific aortic valve disease.

Calcific aortic valve disease (CAVD) is a heart valve disorder characterized primarily by calcification of the aortic valve, resulting in stiffness and dysfunction of the valve. CAVD is prevalent among aging populations and is linked to factors such as hypertension, dyslipidemia, tobacco use, and genetic predisposition, and can result in becoming a growing economic and health burden. Once aortic valve calcification occurs, it will inevitably progress to aortic stenosis. At present, there are no medications available that have demonstrated effectiveness in managing or delaying the progression of the disease. In this study, we mined four publicly available microarray datasets (GSE12644 GSE51472, GSE77287, GSE233819) associated with CAVD from the GEO database with the aim of identifying hub genes associated with the occurrence of CAVD and searching for possible biological targets for the early prevention and diagnosis of CAVD. This study provides preliminary evidence for therapeutic and preventive targets for CAVD and may provide a solid foundation for subsequent biological studies.

Romidepsin exhibits anti-esophageal squamous cell carcinoma activity through the DDIT4-mTORC1 pathway.

Esophageal squamous cell carcinoma (ESCC) is one of the most common human malignancies worldwide and is associated with high morbidity and mortality. Current treatment options are limited, highlighting the need for development of novel effective agents. Here, a high-throughput drug screening (HTS) was performed using ESCC cell lines in both two- and three-dimensional culture systems to screen compounds that have anti-ESCC activity. Our screen identified romidepsin, a histone deactylase inhibitor, as a potential anti-ESCC agent. Romidepsin treatment decreased cell viability, induced apoptosis and cell cycle arrest in ESCC cell lines, and these findings were confirmed in ESCC cell line-derived xenografted (CDX) mouse models. Mechanically, romidepsin induced transcriptional upregulation of DNA damage-inducible transcript 4 (DDIT4) gene by histone hyperacetylation at its promoter region, leading to the inhibition of mammalian target of rapamycin complex 1 (mTORC1) pathway. Furthermore, romidepsin exhibited better efficacy and safety compared to the conventional therapeutic drugs in ESCC patient-derived xenografted (PDX) mouse models. These data indicate that romidepsin may be a novel option for anti-ESCC therapy.

Concomitant tricuspid valve surgery in patients undergoing left ventricular assist device: a systematic review and meta-analysis.

INTRODUCTION: This study aims to investigate the effect of concomitant tricuspid valve surgery (TVS) during left ventricular assist device (LVAD) implantation due to the controversy over the clinical outcomes of concomitant TVS in patients undergoing LVAD. METHODS: A systematic literature search was performed in PubMed and EMbase from the inception to 1 August 2023. Studies comparing outcomes in adult patients undergoing concomitant TVS during LVAD implantation (TVS group) and those who did not (no-TVS group) were included. The primary outcomes were right heart failure (RHF), right ventricular assist device (RVAD) implantation, and early mortality. All meta-analyses were performed using random-effects models, and a two-tailed P <0.05 was considered significant. RESULTS: Twenty-one studies were included, and 16 of them were involved in the meta-analysis, with 660 patients in the TVS group and 1291 in the no-TVS group. Patients in the TVS group suffered from increased risks of RHF [risk ratios (RR)=1.31, 95% CI: 1.01-1.70, P =0.04; I2 =38%, pH =0.13), RVAD implantation (RR=1.56, 95% CI: 1.16-2.11, P =0.003; I2 =0%, pH =0.74), and early mortality (RR=1.61, 95% CI: 1.07-2.42, P =0.02; I2 =0%, pH =0.75). Besides, the increased risk of RHF holds true in patients with moderate to severe tricuspid regurgitation (RR=1.36, 95% CI: 1.04-1.78, P =0.02). TVS was associated with a prolonged cardiopulmonary bypass time. No significant differences in acute kidney injury, reoperation requirement, hospital length of stay, or ICU stay were observed. CONCLUSIONS: Concomitant TVS failed to show benefits in patients undergoing LVAD, and it was associated with increased risks of RHF, RVAD implantation, and early mortality.

Machine learning-based radiomics to distinguish pulmonary nodules between lung adenocarcinoma and tuberculosis.

BACKGROUND: Radiomics is increasingly utilized to distinguish pulmonary nodules between lung adenocarcinoma (LUAD) and tuberculosis (TB). However, it remains unclear whether different segmentation criteria, such as the inclusion or exclusion of the cavity region within nodules, affect the results. METHODS: A total of 525 patients from two medical centers were retrospectively enrolled. The radiomics features were extracted according to two regions of interest (ROI) segmentation criteria. Multiple logistic regression models were trained to predict the pathology: (1) The clinical model relied on clinical-radiological semantic features; (2) The radiomics models (radiomics+ and radiomics-) utilized radiomics features from different ROIs (including or excluding cavities); (3) the composite models (composite+ and composite-) incorporated both above. RESULTS: In the testing set, the radiomics+/- models and the composite+/- models still possessed efficient prediction performance (AUC ≥ 0.94), while the AUC of the clinical model was 0.881. In the validation set, the AUC of the clinical model was only 0.717, while that of the radiomics+/- models and the composite+/- models ranged from 0.801 to 0.825. The prediction performance of all the radiomics+/- and composite+/- models were significantly superior to that of the clinical model (p < 0.05). Whether the ROI segmentation included or excluded the cavity had no significant effect on these models (radiomics+ vs. radiomics-, composite+ model vs. composite-) (p > 0.05). CONCLUSIONS: The present study established a machine learning-based radiomics strategy for differentiating LUAD from TB lesions. The ROI segmentation including or excluding the cavity region may exert no significant effect on the predictive ability.

SH2D4A inhibits esophageal squamous cell carcinoma progression through FAK/PI3K/AKT signaling pathway.

Esophageal squamous cell carcinoma (ESCC), one of the most common malignant tumors, is now afflicting approximately 80% of patients diagnosed with esophageal cancers. The therapeutic effect and prognosis of ESCC remain inadequate due to the unusual early symptoms and rapid malignant progression. SH2 Domain containing 4 A (SH2D4A) is downregulated in malignancies and is closely associated with tumor progression. However, neither the biological functions nor the fundamental mechanisms of SH2D4A on ESCC are known. In this study, it was found that SH2D4A is downregulated in ESCC tissues and cell lines. Incorporating immunohistochemistry and clinicopathological findings, we determined that decreased SH2D4A expression was substantially associated with adverse clinical outcomes. Overexpression of SH2D4A inhibited cell proliferation and migration, whereas suppressing SH2D4A has the opposite effect. SH2D4A mechanistically inhibited cells from proliferating and migrating through the FAK/PI3K/AKT signaling pathway. Furthermore, the results of xenograft tumor growth confirmed the preceding findings. In conclusion, our findings reveal that SH2D4A is a gene which can serve as a cancer suppressor in ESCC and may inhibits the ESCC progression by interfering with the FAK/PI3K/AKT signaling pathway. SH2D4A could act as a target for diagnostic or therapeutic purpose in ESCC.

A Machine Learning Study on High Thermal Conductivity Assisted to Discover Chalcogenides with Balanced Infrared Nonlinear Optical Performance.

Exploration of novel nonlinear optical (NLO) chalcogenides with high laser-induced damage thresholds (LIDT) is critical for mid-infrared (mid-IR) solid-state laser applications. High lattice thermal conductivity (κL ) is crucial to increasing LIDT yet often neglected in the search for NLO crystals due to lack of accurate κL data. A machine learning (ML) approach to predict κL for over 6000 chalcogenides is hereby proposed. Combining ML-generated κL data and first-principles calculation, a high-throughput screening route is initiated, and ten new potential mid-IR NLO chalcogenides with optimal bandgap, NLO coefficients, and thermal conductivity are discovered, in which Li2 SiS3 and AlZnGaS4 are highlighted. Big-data analysis on structural chemistry proves that the chalcogenides having dense and simple lattice structures with low anisotropy, light atoms, and strong covalent bonds are likely to possess higher κL . The four-coordinated motifs in which central cations show the bond valence sum of +2 to +3 and are from IIIA, IVA, VA, and IIB groups, such as those in diamond-like defect-chalcopyrite chalcogenides, are preferred to fulfill the desired structural chemistry conditions for balanced NLO and thermal properties. This work provides not only an efficient strategy but also interpretable research directions in the search for NLO crystals with high thermal conductivity.

Calcium channel blockers and clinical outcomes in patients with continuous-flow left ventricular assist devices.

AIMS: Current guidelines suggest calcium channel blockers (CCBs) as the second or third option for blood pressure management in patients with left ventricular assist device (LVAD). However, the clinical outcomes of patients with LVAD who receive CCBs remain unclear. Our study aims to analyse the association of CCBs with clinical outcomes in patients after LVAD implantation. METHODS AND RESULTS: This is a retrospective analysis based on the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) from 2006 to 2017, and adult patients who were alive with LVAD and CCB treatment information at 6 months after implantation were included. Among 10 717 patients, 1369 received CCBs 6 months after implantation, and there was an increasing trend of CCB use after LVAD. Patients receiving CCB therapy at 6 months had a similar 5 year survival rate to those not receiving CCB [49.6%, 95% confidence interval (CI): 47.5-51.7% vs. 51.1%, 95% CI: 45.3-56.7%]. In both Cox and competing risk regressions after adjusting for confounding factors, CCB treatment at 6 months after implantation was not associated with long-term mortality [hazard ratio (HR): 1.03, 95% CI: 0.91-1.17, P = 0.624 and subdistribution HR (SHR): 1.07, 95% CI: 0.95-1.22, P = 0.260]. Consistently, in time-varying models, CCB treatment was not linked to long-term mortality (HR: 0.97, 95% CI: 0.87-1.09, P = 0.682 and SHR: 1.05, 95% CI: 0.94-1.18, P = 0.359). This null association remained in subgroup analysis according to device strategy and propensity-matching analyses. Neurological dysfunction, stroke, bleeding, rehospitalization, and renal dysfunction were more likely to occur among those with CCB when compared with those without CCB treatment. CONCLUSIONS: In patients with LVAD, CCB therapy fails to show benefits in long-term survival and is associated with increased incidences of neurological dysfunction, bleeding, renal dysfunction, and rehospitalization.

Prognostic value of circulating tumor DNA in operable non-small cell lung cancer: a systematic review and reconstructed individual patient-data based meta-analysis.

BACKGROUND: This reconstructed individual patient data (IPD)-based meta-analysis is aimed to summarize the current findings and comprehensively investigate the predictive value of circulating tumor DNA (ctDNA) in operable non-small cell lung cancer (NSCLC). METHODS: PubMed, Cochrane and Embase were searched to include potentially eligible studies. The primary outcomes included progression-free survival (DFS) by ctDNA status at baseline, postoperative, and longitudinal timepoints. The IPD-based survival data was retracted and used in reconstructed IPD-based meta-analysis. Subgroup analysis was implemented based on the baseline characteristics. RESULTS: Totally, 28 studies were involved, including 15 full-length articles (1686 patients) for IPD-based synthesis and 20 studies for conventional meta-analysis. The IPD-based meta-analysis discovered that patients with positive ctDNA status at the baseline (hazard ratio, HR = 3.73, 95% confidential interval, CI: 2.95-4.72), postoperative (3.96, 2.19-7.16), or longitudinal timepoints (12.33, 8.72-17.43) showed significantly higher risk of recurrence. Patients with persistent ctDNA-negative status had the lowest recurrence rate, and the negative conversion of ctDNA from baseline to postoperative timepoints was correlated with elevated DFS. Subgroup analyses suggested that stage II-III patients with ctDNA-positive status may achieve preferable therapeutic outcomes. CONCLUSIONS: Plasm ctDNA monitoring shows excellent clinical significance at the tested timepoints. Perioperative conversion of ctDNA status may indicate the therapeutic effect of radical surgery. Postoperative adjuvant therapy may be determined according to the ctDNA status. TRAIL REGISTRATION: CRD42022304445.

Causal Role for Neutrophil Elastase in Thoracic Aortic Dissection in Mice.

BACKGROUND: Thoracic aortic dissection (TAD) is a life-threatening aortic disease without effective medical treatment. Increasing evidence has suggested a role for NE (neutrophil elastase) in vascular diseases. In this study, we aimed at investigating a causal role for NE in TAD and exploring the molecular mechanisms involved. METHODS: ß-aminopropionitrile monofumarate was administrated in mice to induce TAD. NE deficiency mice, pharmacological inhibitor GW311616A, and adeno-associated virus-2-mediated in vivo gene transfer were applied to explore a causal role for NE and associated target gene in TAD formation. Multiple functional assays and biochemical analyses were conducted to unravel the underlying cellular and molecular mechanisms of NE in TAD. RESULTS: NE aortic gene expression and plasma activity was significantly increased during ß-aminopropionitrile monofumarate-induced TAD and in patients with acute TAD. NE deficiency prevents ß-aminopropionitrile monofumarate-induced TAD onset/development, and GW311616A administration ameliorated TAD formation/progression. Decreased levels of neutrophil extracellular traps, inflammatory cells, and MMP (matrix metalloproteinase)-2/9 were observed in NE-deficient mice. TBL1x (F-box-like/WD repeat-containing protein TBL1x) has been identified as a novel substrate and functional downstream target of NE in TAD. Loss-of-function studies revealed that NE mediated inflammatory cell transendothelial migration by modulating TBL1x-LTA4H (leukotriene A4 hydrolase) signaling and that NE regulated smooth muscle cell phenotype modulation under TAD pathological condition by regulating TBL1x-MECP2 (methyl CpG-binding protein 2) signal axis. Further mechanistic studies showed that TBL1x inhibition decreased the binding of TBL1x and HDAC3 (histone deacetylase 3) to MECP2 and LTA4H gene promoters, respectively. Finally, adeno-associated virus-2-mediated Tbl1x gene knockdown in aortic smooth muscle cells confirmed a regulatory role for TBL1x in NE-mediated TAD formation. CONCLUSIONS: We unravel a critical role of NE and its target TBL1x in regulating inflammatory cell migration and smooth muscle cell phenotype modulation in the context of TAD. Our findings suggest that the NE-TBL1x signal axis represents a valuable therapeutic for treating high-risk TAD patients.

Risk assessment for postoperative venous thromboembolism using the modified Caprini risk assessment model in lung cancer.

Background: Postoperative venous thromboembolism (VTE) is a well-documented cause of morbidity and mortality in lung cancer patients. However, risk identification remains limited. In this study, we sought to analyze the risk factors for VTE and verify the predictive value of the modified Caprini risk assessment model (RAM). Methods: This prospective single-center study included patients with resectable lung cancer who underwent resection between October 2019 and March 2021. The incidence of VTE was estimated. Logistic regression was used to analyze the risk factors for VTE. Receiver operating characteristic (ROC) curve analysis was performed to test the ability of the modified Caprini RAM to predict VTE. Results: The VTE incidence was 10.5%. Several variables, including age, D-dimer, hemoglobin (Hb), bleeding, and patient confinement to bed were significantly associated with VTE after surgery. The difference between the VTE and non-VTE groups in the high-risk levels was statistically significant (P<0.001), while the low and moderate risk levels showed no significant difference. The combined use of the modified Caprini score and the Hb and D-dimer levels showed an area under the curve (AUC) was 0.822 [95% confidence interval (CI): 0.760-0.855. P<0.001]. Conclusions: The risk-stratification approach of the modified Caprini RAM is not particularly valid after lung resection in our population. The use of the modified Caprini RAM combined with Hb and D-dimer levels shows a good diagnostic performance for VTE prediction in patients with lung cancer undergoing resection.

Presence and impact of anemia in patients supported with left ventricular assist devices.

BACKGROUND: Data on anemia and its effects on patients supported with continuous-flow left ventricular assist devices (LVADs) are lacking. OBJECTIVES: This study sought to describe the presence of anemia over time and investigate its association with mortality, quality of life, exercise capacity, and adverse events in LVAD patients. METHODS: Adults receiving durable LVADs between 2008 and 2017 were identified from the INTERMACS database. The full cohort was stratified according to anemia severity (no anemia, mild, and moderate-severe). RESULTS: The analysis of 19,509 patients (females: 21.2%, age: 56.9 ± 12.9 years) showed that moderate-severe anemia affected 45.2% of patients at baseline, 33.5% of them at 6 months, and 32.3% in the fourth year after implantation. The presence of normal hemoglobin was 24.4% before surgery, 32.5% at 6 months, and 36.6% at 4 years after implantation. Multivariable linear mixed-effect regression revealed that the average hemoglobin over time was significantly lower (ß, -0.233, 95% confidence interval (CI): -0.282 to -0.185), and the reduction of hemoglobin over time was bigger (ß, -0.032 95% CI: -0.035 to -0.028) for LVAD nonsurvivors compared with LVAD survivors. Adjusted Cox regression showed that the severity of preimplant anemia was associated with higher mortality (HR, mild: 1.19; 95% CI: 1.05-1.35 and moderate-severe: 1.44; 95% CI: 1.28-1.62), with similar results in competing risk regression. Anemia progression during follow-up was associated with decreased Kansas City Cardiomyopathy Questionnaire scores and shorter 6-minute walk distances. CONCLUSIONS: In patients supported with LVADs, anemia is a frequent comorbidity, and deterioration over time is associated with poor prognosis.

Neoadjuvant camrelizumab plus chemotherapy in locally advanced oesophageal squamous cell carcinoma: a retrospective cohort study.

BACKGROUND: Neoadjuvant therapy is recommended to improve the prognosis of oesophageal squamous cell carcinoma (ESCC). As a PD-1 inhibitor developed in China, camrelizumab is more accessible and available for Chinese ESCC patients. Camrelizumab plus neoadjuvant chemotherapy has shown promising efficacy with acceptable toxicity for resectable ESCC in the NIC-ESCC2019 trial. However, this was a single-arm trial, so we conducted a retrospective cohort study to compare neoadjuvant camrelizumab plus chemotherapy with neoadjuvant chemotherapy alone in terms of the safety and efficacy in patients with locally advanced ESCC. METHODS: Between January 2017 and December 2021, patients with stage II-IVa ESCC who received neoadjuvant therapy at the First Affiliated Hospital of Chongqing Medical University and underwent radical oesophagectomy were enrolled in our study. These included 19 patients who received neoadjuvant chemotherapy plus camrelizumab (group 1) and 40 patients who only received neoadjuvant chemotherapy (group 2). RESULTS: The baseline characteristics of the patients were comparable between the two groups. The pathological complete response (pCR) rate in group 1 was significantly higher than that in group 2 (26.3% vs. 2.5%, P = 0.018). All patients in group 1 achieved complete resection (R0), compared with 39 (97.5%) patients in group 2. Adverse events occurred in 16 (84%) patients in group 1 versus 35 (87.5%) patients in group 2. No grade ≥ 4 adverse events occurred in either group. No significant difference was found in surgical outcomes or postoperative complications. The 90-day mortality rate was comparable between the two groups (1 patient died in group 1 versus 2 patients in group 2). CONCLUSIONS: Neoadjuvant camrelizumab plus chemotherapy followed by surgery was associated with a promising pCR rate and a manageable safety profile for patients with locally advanced ESCC.

Immunocyte count combined with CT features for distinguishing pulmonary tuberculoma from malignancy among non-calcified solitary pulmonary solid nodules.

Background: Tuberculoma is the most common type of surgically removed benign solid solitary pulmonary nodule (SPN) and can lead to a high risk of misdiagnoses for clinicians. This study aimed to discuss the value of the immunocyte count combined with computed tomography (CT) features in distinguishing pulmonary tuberculoma from malignancy among non-calcified solid SPNs. Methods: Forty-eight patients with pulmonary tuberculoma and 52 patients with lung cancer were retrospectively included in our study. Univariate and multivariate analyses were conducted to screen the independent predictors. Receiver operating characteristic (ROC) analysis was performed to investigate the validity of the predictive model. Results: The univariate and multivariate analyses revealed that a coarse margin, vacuole, lobulation, pleural indentation, cluster of differentiation (CD)3+ T-lymphocyte count, and CD4+ T-lymphocyte count were independent predictors for distinguishing pulmonary tuberculoma from malignancy. The sensitivity, specificity, accuracy, and the area under the ROC curve of the model comprising the CD3+ T-lymphocyte count were 79.2%, 75%, 74.5%, and 0.845 [95% confidence interval (CI), 0.759-0.910], respectively, and those of the model involving the CD4+ T-lymphocyte count were 77.1%, 78.8%, 77.1%, and 0.857 (95% CI, 0.773-0.919), respectively. Conclusions: Immunocyte count combined with CT features is efficient in distinguishing pulmonary tuberculoma from malignancy among non-calcified solid SPNs and has applicable clinical value.

Identification of key biomarkers and immune infiltration in the thoracic acute aortic dissection by bioinformatics analysis.

BACKGROUND: Thoracic acute aortic dissection (TAAD), one of the most fatal cardiovascular diseases, leads to sudden death, however, its mechanism remains unclear. METHODS: Three Gene Expression Omnibus datasets were employed to detect differentially expressed genes (DEGs). A similar function and co-expression network was identified by weighted gene co-expression network analysis. The least absolute shrinkage and selection operator, random forest, and support vector machines-recursive feature elimination were utilized to filter diagnostic TAAD markers, and then screened markers were validated by quantitative real-time PCR and another independent dataset. CIBERSORT was deployed to analyze and evaluate immune cell infiltration in TAAD tissues. RESULTS: Twenty-five DEGs were identified and narrowed down to three after screening. Finally, two genes, SLC11A1 and FGL2, were verified by another dataset and qRT-PCR. Function analysis revealed that SLC11A1 and FGL2 play significant roles in immune-inflammatory responses. CONCLUSION: SLC11A1 and FGL2 are differently expressed in aortic dissection and may be involved in immune-inflammatory responses.

Effectiveness and safety of camrelizumab in inoperable or advanced non-small cell lung cancer patients: a multicenter real-world retrospective observational study (CTONG2004-ADV).

Background: Camrelizumab plus chemotherapy have been approved as standards for the treatment of advanced non-small cell lung cancer (NSCLC) patients based on two phase III trials. However, clinical trial results may not be representative of the general population, as clinical trials often have specific inclusion and exclusion criteria. Our research aims to investigate the real-world effectiveness and safety of camrelizumab in inoperable or advanced NSCLC patients. Methods: This multicenter retrospective observational study included inoperable or advanced pathologically confirmed NSCLC patients who received at least one dose of camrelizumab at 22 hospitals. Clinical and follow-up data of camrelizumab were collected retrospectively from the medical records. The primary outcome was the objective response rate (ORR) and secondary outcomes were disease control rate (DCR), 6-month progression-free survival (PFS), overall survival (OS), and treatment-related adverse events (TRAEs). Multivariate logistic and Cox regression analyses were applied to identify potential predictive factors of ORR and PFS, respectively. Results: Between July 2019 and March 2021, 336 patients were included. Adenocarcinoma was seen in 58.4% and stage IV disease in 69.3%. Twenty-nine (8.6%) had liver metastasis at baseline. Most patients received camrelizumab in the first-line setting (74.1%) and in combination with chemotherapy (60.7%). The ORR was 40.2% [95% confidence interval (CI): 34.9-45.6%] and DCR was 85.1% (95% CI: 81.3-88.9%), while the 6-month PFS and OS rates were 73.0% (95% CI: 67.1-78.0%) and 93.1% (95% CI: 89.8-95.4%), respectively. In multivariate analyses, liver metastasis [odds ratio (OR), 0.324; 95% CI: 0.115-0.915; P=0.033] and increasing lines of camrelizumab treatment (vs. first line, second line: OR, 0.347; 95% CI: 0.162-0.741; P=0.006; ≥ third line: OR, 0.126; 95% CI: 0.043-0.367; P<0.001) were negatively associated, while a longer duration of camrelizumab treatment was positively associated with ORR and PFS. TRAEs were recorded in 164 (48.8%) patients, without new safety signal. Conclusions: We conducted a comprehensive overview of the effectiveness and safety profile of camrelizumab in a broader NSCLC population in real world NSCLC patients, and subgroup analysis indicated the presence of liver metastasis was associated with worse outcomes.

Functional Preserving Sublobectomy: A Novel Method for Sublobectomy.

We introduce a new method for sublobectomy. It utilizes the easiness and rapidity of wedge resection, and the accuracy and functional preserving of anatomical segmentectomy. It can preserve lung function with less sacrifice of lung parenchyma.

Characteristics and Outcome of Patients With a History of Cancer Undergoing Durable Left Ventricular Assist Device Implantation.

BACKGROUND: Patients with cancer (patients with a history of cancer) with advanced heart failure are increasing, but unlikely to be transplanted, and left ventricular assist device (LVAD) is an alternative strategy. This study investigates the characteristics and outcomes of patients with cancer undergoing durable LVAD. METHODS: Adult patients with a history of cancer who received LVADs were identified from INTERMACS (Interagency Registry for Mechanically Assisted Circulatory Support) registry: 2008 and 2017. Characteristics and outcomes between patients with cancer and those without cancer were compared, and subgroup analyses of cancer therapy-induced cardiomyopathy (CCM) and non-CCM were also conducted. RESULTS: Overall, 1273 (6.5%) patients had a history of cancer, including 289 (22.7%) with CCM and 984 (77.3%) with non-CCM as the primary reason for heart failure. Patients with cancer had shorter median survival (3.72 versus 3.97 years, log-rank P=0.002), and multivariable Cox and competing risk regressions revealed that a history of cancer was associated with reduced survival (hazard ratio, 1.14 [95% CI, 1.04-1.26]; P=0.005; subdistribution hazard ratio, 1.24 [95% CI, 1.13-1.36]; P<0.001) and decreased incidence of heart transplantation. There was no significant difference in mortality between patients with CCM-induced heart failure and patients without cancer. Patients with cancer experienced an increased risk of bleeding, and age, INTERMACS profile, albumin, dialysis, and blood urea nitrogen were associated with mortality in these patients. CONCLUSIONS: A history of cancer is associated with mildly reduced survival, lower incidence of heart transplantation, and increased risk of bleeding after LVAD, whereas the survival in patients with cancer with CCM-induced heart failure is similar to those without cancer. LVAD implantation in patients with cancer is very well possible.

Impact of delayed veno-venous extracorporeal membrane oxygenation weaning on postoperative rehabilitation of lung transplantation: a single-center comparative study.

Veno-venous extracorporeal membrane oxygenation (VV-ECMO) is a reliable and effective extracorporeal life support during lung transplantation (LTx). However, the clinical benefit of delayed VV-ECMO weaning remains unclear. The current study aims to investigate whether delayed weaning of VV-ECMO is more beneficial to the rehabilitation for lung transplant patients. Patients who underwent LTx with VV-ECMO between January 2017 and January 2019 were included. Enrollment of patients was suitable for weaning off ECMO immediately after surgery. Randomization was performed in the operating room. Postoperative outcomes were compared between the two groups. Besides, univariate and multivariable logistic regressions were performed to estimate risk of postoperative complications. Compared to VV-ECMO weaning immediately after LTx, delayed weaning was associated with shorter hospital length of stay (days, 31 vs. 46; P < 0.05), lower incidence of noninvasive ventilation (4.3% vs. 24.4%; P < 0.05), primary graft dysfunction (PGD) (6.4% vs. 29.3%; P < 0.05), atrial fibrillation (AF) (4.3% vs. 22%, P < 0.05), and respiratory failure (4.3% vs. 19.5%; P < 0.05). Multivariable logistic regressions revealed that VV-ECMO weaning after LTx was independently correlated with increased risk of developing PGD [odds ratio (OR), 5.97, 95% CI 1.16-30.74], AF (OR, 6.87, 95% CI 1.66-28.47) and respiratory failure (OR, 6.02, 95% CI 1.12-32.49) by comparison of delayed VV-ECMO weaning. Patients with delayed VV-ECMO weaning are associated with lower complications and short hospital length of stay, while it relates to longer mechanical ventilation. These findings suggest that delayed VV-ECMO after LTx can facilitate rehabilitation.