Long-term Survival Rate Of Patients Research Articles

Clinical efficacy of pancreas-preserving distal pancreatectomy for the treatment of pancreatic ductal adenocarcinoma

The long-term survival rate of patients with pancreatic ductal adenocarcinoma has improved alongside the development of multidisciplinary treatment, and there is now demand for less invasive surgery that maintains postoperative pancreatic function. We evaluated the efficacy of pancreas-preserving distal pancreatectomy in terms of oncologic parameters and postoperative pancreatic function. The data of 98 consecutive patients who underwent distal pancreatectomy for the treatment of pancreatic ductal adenocarcinoma between 2012 and 2022 in our institution were retrospectively analyzed. The surgical outcomes, overall survival, and postoperative pancreatic function were compared between pancreas-preserving distal pancreatectomy, in which the pancreatic stump was distal to the left margin of the portal vein on postoperative computed tomography, and conventional distal pancreatectomy. Sixteen patients (16%) underwent pancreas-preserving distal pancreatectomy. Fewer lymph nodes were dissected in the pancreas-preserving distal pancreatectomy group than the conventional distal pancreatectomy group (19 vs 31, respectively; P < .01); however, the R0 resection rate (94% vs 93%, respectively; P= 1.00), recurrence-free survival, and overall survival were similar. Similar results were obtained in an analysis limited to patients with pancreatic ductal adenocarcinoma in the pancreatic tail. Patients who underwent pancreas-preserving distal pancreatectomy were less likely to develop worsening of their diabetes than those who underwent conventional distal pancreatectomy (19% vs 39%, respectively; P= .16). Nonalcoholic fatty liver disease newly developed in 22% of the patients who underwent conventional distal pancreatectomy but in none of those who underwent pancreas-preserving distal pancreatectomy (P= .04). The pancreatic transection site should be distally located to preserve postoperative pancreatic function when R0 resection can be achieved.

ZFP36L2 Is a Potential Prognostic Marker of IL1β+ Osteosarcoma.

Background: Osteosarcoma stands as the predominant bone malignancy afflicting children and young adults. Despite strides in treatment, the enduring reality is that the long-term survival rates for patients grappling with recurrences and metastases linger at a mere 30%. This underscores the pressing demand for novel prognostic markers and therapeutic avenues to improve outcomes and offer hope to those battling this formidable disease. ZFP36L2, a member of the tristetraprolin family of CCCH zinc finger proteins, stands out for its pivotal role in posttranscriptional modifications and its ability to modify tumor microenvironments. Methods: We obtained RNA-seq data from TCGA and GTEx cohorts to investigate the expression of ZFP36L2 in tumor and normal tissues. We also utilized GO/KEGG analysis and immune infiltration analysis to verify the relationship between ZFP36L2 and immune cells. A Kaplan-Meier survival curve was used to study the relationship between ZFP36L2 and IL1β in osteosarcoma. Single-cell data analysis and cell-cell communication analysis were used to discover the therapeutic potential of ZFP36L2 in osteosarcoma. Results: This study elucidates the specific expression pattern of ZFP36L2 in tumors. ZFP36L2 is associated with metastasis in sarcoma, but has no statistically significant correlation with survival rate. ZFP36L2 has been shown to be associated with T cells and macrophages in the tumor microenvironment through GO/KEGG analysis and immune infiltration analysis. The survival analysis results show that ZFP36L2 can serve as a biomarker in IL1β+ osteosarcoma. Single-cell sequencing analysis shows that ZFP36L2 is present in IL1β+ macrophages. Cell-cell communication analysis indicates that ZFP36L2 targets TNF in IL1β+ osteosarcoma, thereby improving prognosis. Conclusions: ZFP36L2 has potential as a prognostic marker in IL1β+ osteosarcoma patients.

Platelet-to-albumin ratio: a potential biomarker for predicting all-cause and cardiovascular mortality in patients undergoing peritoneal dialysis

BackgroundAlthough peritoneal dialysis (PD) is an efficient therapy for renal replacement, the long-term survival rate of patients undergoing PD remains low. The platelet-to-albumin ratio (PAR), recently identified as a parameter of inflammatory and nutritional status, is associated with an adverse prognosis for various diseases. However, the association between the serum PAR and prognosis of patients undergoing PD is poorly understood. This study aimed to evaluate whether the PAR is a reliable predictor of cardiovascular disease (CVD) and all-cause mortality in patients undergoing PD.MethodsThis multicenter cohort study enrolled patients undergoing PD from January 1, 2009, to September 30, 2018. The patients were divided into four groups according to the quartiles of their baseline PAR. The primary endpoint was all-cause and CVD-related mortality. Cox proportional hazard models were used to determine the association between the PAR and all-cause or CVD-related mortality. The receiver operating characteristic (ROC) curve was utilized to compare the performance among PAR and other inflammatory indicators. C-statistic, net reclassification improvement (NRI), and integrated discrimination improvement (IDI) were applied to examine the incremental prognostic value of PAR compared with baseline model for predicting all-cause and CVD mortality.ResultsA total of 2825 patients were included. During the follow-up period of 47.5 ± 28.3 months, 747 (26.4%) mortality cases were observed, of which 415 (55.6%) were CVD-related. Compared with the Q1 (PAR < 4.43), placement in Q4 (PAR > 7.27) was associated with an increased risk of all-cause mortality and CVD mortality (p < 0.001). The adjusted restricted cubic spline analysis indicated that the relationship of the PAR with all-cause and cardiovascular mortality was linear (p for nonlinearity = 0.289 and 0.422, respectively). No positive correlations were shown in the interaction tests. PAR exhibited superior predictive value for mortality compared to other inflammatory indicators, with a respective AUC value of 0.611 (P < 0.001) for all-cause mortality and 0.609 (P < 0.001) for cardiovascular mortality. According to the C-statistic, continuous NRI and IDI, the addition of PAR to the baseline model yielded a moderate but significant improvement in outcome prediction.ConclusionsThe PAR is an independent prognostic factor associated with all-cause and cardiovascular mortality in patients undergoing PD.

Single-cell RNA sequencing identifies a subtype of FN1 + tumor-associated macrophages associated with glioma recurrence and as a biomarker for immunotherapy

BackgroundGlioma is the most common primary malignant tumor in the brain, and even with standard treatments including surgical resection, radiotherapy, and chemotherapy, the long-term survival rate of patients remains unsatisfactory. Recurrence is one of the leading causes of death in glioma patients. The molecular mechanisms underlying glioma recurrence remain unclear.MethodsOur study utilized single-cell sequencing, spatial transcriptomics, and RNA-seq data to identify a subtype of FN1 + tumor-associated macrophages (FN1 + TAMs) associated with glioma recurrence.ResultsThis study revealed an increased abundance of FN1 + TAMs in recurrent gliomas, indicating their potential involvement as a critical factor in glioma recurrence. A negative correlation was observed between the abundance of FN1 + TAMs in primary gliomas and the interval time to recurrence, suggesting poor prognosis for glioma patients with high levels of FN1 + TAMs. Further investigation showed that FN1 + TAMs were enriched in hypoxic tumor regions, implying that metabolic changes in tumors drive the production and recruitment of FN1 + TAMs. Additionally, FN1 + TAMs were found to contribute to the regulation of an immunosuppressive microenvironment in gliomas, and their abundance might serve as an indicator of patients’ sensitivity to immunotherapy. Finally, we developed a user-friendly website, PRIMEG (http://www.szflab.site/PRIMEG/), for exploring the immune microenvironment of primary and recurrent gliomas.ConclusionOur findings highlight a subtype of FN1 + TAMs associated with glioma recurrence, providing new insights into potential therapeutic targets. Moreover, the abundance of FN1 + TAMs hold promise for predicting immune therapy response and aiding in more precise risk stratification of recurrent glioma patients.

Advantages and rational application of indocyanine green fluorescence in pulmonary nodule surgery: a narrative review.

The early detection and early treatment of high-risk pulmonary nodules directly affect the long-term survival rate of patients. However, conventional nodule localization methods, such as hook-wire, technetium-99m, and methylene blue are associated with issues such as a high-frequency of complications, low patient tolerance, serious side effects, and inability to identify pigmented lungs. For patients who require segmentectomy, there is often a lack of effective path planning, resulting in insufficient resection margins or excessive loss of lung function. Therefore, effective and rational nodule localization and surgical approaches are crucial. This narrative review aimed to evaluate the advantages of indocyanine green (ICG) fluorescence in pulmonary nodule surgery and clarify its application in various types of patients. We searched the PubMed and Web of Science databases from January 2010 to January 2024 using the terms "localization of pulmonary nodules", "localization of pulmonary nodules AND indocyanine green", "localization of pulmonary nodules AND complication", "localization of pulmonary nodules AND surgical planning", and "localization of pulmonary nodules AND underlying lung disease". Information used to write this narrative review was from clinical phenomena, statistical data, and authors' conclusions. The commonly used localization methods of pulmonary nodule such as computed tomography (CT)-guided percutaneous placement of hook-wire are accompanied with serious complications: including hemopneumothorax and ache. Meanwhile, routine dye commonly fails to localize the nodules in patients with anthracosis. ICG with the enhanced permeability and retention (EPR) effect can be used effectively for preoperative and intraoperative localization of pulmonary nodules and its nature of allowing the observance of the condition of pulmonary blood vessels has gradually become a hotspot of research in this field. For nodules with a depth of less than 1 cm, no penetration depth problem is encountered when ICG fluorescence is used. Percutaneous puncture can effectively identify the location of nodules at low cost. Compared with other localization methods, it can effectively avoid problems such as pain, radiation exposure, marker displacement, and the existence of anthrax lesions in the lungs. For patients on whom it is difficult to locate nodules due to tissue results, virtual bronchoscopy or electromagnetic navigation bronchoscopy can effectively identify nodules and reduce complications such as pneumothorax. For patients whose operation is postponed due to fever, sudden cardiovascular and cerebrovascular diseases, there is no risk of nodule localization material detachment by using ICG. ICG can also be used in patients with pulmonary physiological or pathological diseases. Meanwhile, in patients with deep pulmonary nodules, ICG fluorescence can help plan the surgical path, ensure the margin of resection, reduce lung function damage, and prevent bronchial fistula. Therefore, the rational use of ICG fluorescence technology can effectively locate nodules, assist surgeons in planning surgical methods, potentially reducing complications and ultimately improving patient prognosis.

Efficacy of Double Valve Replacement/Repair in Patients with Reduced Left Ventricular Ejection Fractions

Introduction: A reduced left ventricular ejection fraction (LVEF) is a known risk factor for double valve replacement or aortic valve replacement in combination with concomitant mitral valve repair (DVR) and is associated with high morbidity and mortality rates. In this study, we sought to analyze the 30-day mortality and long-term survival rates of patients with reduced LVEFs. Methods: A multicenter, retrospective, observational cohort study of patients who underwent DVR was performed at four centers from January 2016 to December 2021. LVEFs were categorized as 41%–50% (n = 120) or ≤40% (n = 58). For the effects of risk factors on 30-day mortality, binary logistic regression was performed. Survival rates were assessed with the Kaplan–Meier method. Results: A total of 178 patients who underwent DVR were included in this study, of whom 67.42% (n = 120) had LVEFs ranging from 41–50% and 32.58% (n = 58) had LVEFs ≤40%. More mechanical valves and tricuspid valve-forming rings were applied in the LVEF ≤40% group (68.97% versus 53.33%, p = 0.047; 31.03% versus 10.83%, p = 0.001). The 30-day mortality rates of DVR patients with LVEFs ranging from 41–50% and ≤40% were 8.33% and 17.24%, respectively (p = 0.078). During the follow-up period, there were no significant differences in long-term survival (log rank p = 0.75). On multivariable logistic regression analysis, age &gt;65 years [odds ratio (OR): 5.559, 95% confidence interval (CI): 1.668–18.524, p = 0.005] and cardiopulmonary bypass (CPB) duration &gt;200 min (OR: 5.031, 95% CI: 1.773–14.277, p = 0.002) were significantly associated with the likelihood of 30-day mortality. Conclusions: Although the differences in 30-day mortality and long-term survival rates between DVR patients with LVEFs ranging from 41–50% and ≤40% were not statistically significant in our cohort, an age &gt;65 years and a CPB duration &gt;200 min were predictors of 30-day mortality.

348. MANAGEMENT OF AORTO-ESOPHAGEAL FIFISTULA SECONDARY AFTER THORACIC ENDOVASCULAR AORTIC REPAIR

Abstract Background Aorto-esophageal fifistula (AEF) is rare with highly fatal conditions and occurs most frequently secondary as a result of oesophageal malignancies, aortic aneurysms, thoracic trauma, and other thoracic surgerys. We evaluated the incidence of AEF after thoracic endovascular aortic repair (TEVAR), and investigated their clinical features, determinants, therapeutic options and results. Raising awareness and vigilance of AEF and developing individualized diagnosis and treatment measures are the key to improve the prognosis. Methods We conducted a voluntary survey in three centres with a thoracic endovascular programme. Results Of the patients who underwent TEVAR between 2010 and 2020,11/423 developed AEF. Aortic pseudoaneurysm was associated with the development of AEF among indications to TEVAR (P&amp;lt;0.05). Besides, emergent and complicated procedures resulted in increased risk of AEF (P&amp;lt;0.05). Five patients were treated conservatively, all of whom died within 30 days. Six patients underwent AEF surgical treatment, with a perioperative mortality of 33% (2/6). At a mean follow-up of 18.7+13.6 months, overall survival was 33% (2/6). Conclusion The incidence of AEF after TEVAR is not negligible and long-term follow-up is required especially for patients submitted to emergent and complicated procedures. Both surgical and endovascular treatment of AEF are associated with high mortality. However, once AEF develops, conservative treatment does not appear to be an optimal management. Timely operation has positive correlation with increase of long-term survival rate of patients.

Long-term outcomes and risk factors for early bacterial infection after pediatric liver transplantation: a prospective cohort study.

Liver transplantation (LT) is the most efficient treatment for pediatric patients with end-stage liver diseases, while bacterial infection is the leading reason for post-transplant mortality. The present study is to explore the outcomes and risk factors of early bacterial infection (within 1 months) after pediatric LT. In this prospective cohort study, 1316 pediatric recipients [median (IQR) age: 9.1 (6.3-28.0) months; male: 48.0%; median (IQR) follow-up time: 40.6 (29.1-51.4) months] who received LT from September 2018 to April 2022 were included. Bacterial culture samples such as sputum, abdominal drainage, blood, and so on were collected when recipients were presented with infective symptoms. Kaplan-Meier analysis was applied to estimate the long-term survival rates and logistic regression was used to identify independent risk factors. To explore the role of pretransplant rectal swab culture (RSC) in reducing post-transplant bacterial infection rate, 188 infant LT recipients [median (IQR) age: 6.8 (5.5-8.1) months; male: 50.5%] from May 2022 to September 2023 were included. Log-binomial regression was used to measure the association of pretransplant RSC screening and post-transplant bacterial infection. The 'Expectation Maximization' algorithm was used to impute the missing data. Bacterial infection was the primary cause for early (38.9%) and overall mortality (35.6%) after pediatric LT. Kaplan-Meier analysis revealed inferior 1-year and 5-year survival rates for recipients with post-transplant bacterial infection (92.6 vs. 97.1%, 91.8 vs. 96.4%, respectively; P <0.001). Among all detected bacteria, Staphylococcus spp. (34.3%) and methicillin-resistant coagulase-negative Staphylococci (43.2%) were the dominant species and multidrug resistant organisms, respectively. Multivariable analysis revealed that infant recipients [adjusted odds ratio (aOR) 1.49; 95% CI: 1.01-2.20], male recipients (aOR, 1.43; 95% CI: 1.08-1.89), high graft-to-recipient weight ratio (aOR, 1.64; 95% CI: 1.17-2.30), positive post-transplant RSC (aOR, 1.45; 95% CI: 1.04-2.02) and nasopharyngeal swab culture (aOR 2.46; 95% CI: 1.72-3.52) were independent risk factors for early bacterial infection. Furthermore, RSC screening and antibiotic prophylaxis before transplantation could result in a relatively lower post-transplant infection rate, albeit without statistical significance (adjusted RR, 0.53; 95% CI: 0.25-1.16). In this cohort study, post-transplant bacterial infection resulted in an inferior long-term patient survival rate. The five identified independent risk factors for post-transplant bacterial infection could guide the prophylaxis strategy of post-transplant bacterial infection in the future. Additionally, pretransplant RSC might decrease post-transplant bacterial infection rate.

Effect of joint-line obliquity on long-term survivorship of total knee arthroplasty: A postoperative phenotype analysis.

Whether the longevity of total knee arthroplasty (TKA) differs between postoperative phenotypes has not been investigated. This study aims to examine which phenotype has a worse long-term survival rate than the reference phenotype (neutral alignment-parallel joint line), and whether joint-line obliquity (JLO) affects the survivorship of TKA. A total of 945 knees that underwent primary TKAs for primary osteoarthritis from January 2000 to January 2009 were included. These were classified into nine postoperative phenotypes based on the combined assessment of the hip-knee-ankle (HKA) angle and JLO, measured on standing radiographs. The 5-, 10- and 15-year survival rates were analysed using Kaplan-Meier methods and log-rank tests. The long-term survival rates of each phenotype were compared with the reference phenotype. There were 55 aseptic mechanical failures within a period of 10.4 ± 5.0 years. The most frequently observed phenotypes were the reference phenotype (n = 527), neutral alignment-lateral joint-line inclination (n = 162), varus alignment-lateral joint-line inclination (n = 104) and varus alignment-parallel joint line (n = 101). The overall failure rate for each phenotype was 3.6%, 3.7%, 18.3% and 7.9%, respectively. Only the 10- and 15-year survival rates of the varus alignment-lateral joint-line inclination phenotype were significantly different from those of the reference phenotype (97%-93% vs. 90%-69%; p = 0.017, <0.001). The lateral joint-line inclination phenotype had an inferior long-term survival rate after varus-aligned TKA. This suggested that alignment and JLO affected the long-term survival rate of patients who underwent TKA. Level III, retrospective cohort study.

Integrated analysis of single-cell RNA sequencing and bulk RNA data reveals gene regulatory networks and targets in dilated cardiomyopathy

Dilated cardiomyopathy (DCM) is a common cause of heart failure, thromboembolism, arrhythmias, and sudden cardiac death. The quality of life and long-term survival rates of patients with dilated DCM have greatly improved in recent decades. Nevertheless, the clinical prognosis for DCM patients remains unfavorable. The primary driving factors underlying the pathogenesis of DCM remain incompletely understood. The present study aimed to identify driving factors underlying the pathogenesis of DCM from the perspective of gene regulatory networks. Single-cell RNA sequencing data and bulk RNA data were obtained from the Gene Expression Omnibus (GEO) database. Differential gene analysis, single-cell genomics analysis, and functional enrichment analysis were conducted using R software. The construction of Gene Regulatory Networks was performed using Python. We used the pySCENIC method to analyze the single-cell data and identified 401 regulons. Through variance decomposition, we selected 19 regulons that showed significant responsiveness to DCM. Next, we employed the ssGSEA method to assess regulons in two bulk RNA datasets. Significant statistical differences were observed in 9 and 13 regulons in each dataset. By intersecting these differentiated regulons and identifying shared targets that appeared at least twice, we successfully pinpointed three differentially expressed targets across both datasets. In this study, we assessed and identified 19 gene regulatory networks that were responsive to the disease. Furthermore, we validated these networks using two bulk RNA datasets of DCM. The elucidation of dysregulated regulons and targets (CDKN1A, SAT1, ZFP36) enhances the molecular understanding of DCM, aiding in the development of tailored therapies for patients.

Prognostic prediction of ovarian cancer based on hierarchical sampling & fine-grained recognition convolution neural network

Ovarian cancer ranks among the deadliest gynecological malignancies, with high-grade serous adenocarcinoma (HGSA) constituting 75 % of ovarian cancer cases and accounting for 80 %–90 % of ovarian cancer-related fatalities. Accurate prognosis prediction for ovarian HGSA is of critical clinical significance. However, existing prognostic analysis methods exhibit suboptimal performance in identifying prognostically relevant pathological markers, making it challenging, even for experienced pathologists, to forecast the prognosis of ovarian HGSA patients accurately. Deep learning holds promise in enhancing prognostic prediction accuracy. However, a significant challenge in this field arises from the impracticality of directly inputting histopathology whole-slide images with millions to billions of pixels into existing deep learning networks for training and inference. To address this issue, we propose a prognostic analysis network for ovarian cancer based on hierarchical sampling and fine-grained recognition. This network comprises a two-stage hierarchical sampling sub-network, a fine-grained image recognition sub-network, and a prognostic analysis sub-network. We assess the system's performance using a pathological dataset of 450 cases of ovarian HGSA diagnosed and treated at the Pathology Department of the West China Second University Hospital of Sichuan University. Results indicate that: (1) The proposed prognostic analysis network based on two-stage hierarchical sampling sub-network can effectively analyze the histopathology whole-slide image; (2) the use of fine-grained image recognition and the introduction of clinical information can improve the performance of HGSA prognosis analysis method, with an improvement range of 4.77–10.66%; and (3) the proposed method can be used for the model analysis of pathological datasets of HGSA. Moreover, this method can be used to explore effective characteristics from the multi-modal dataset through automatic learning with prediction recall, accuracy, and precision rates of 80.0%, 81.1%, and 81.8%, respectively, underscoring its clinical potential. This study reveals the reliability and effectiveness of the proposed prognosis evaluation method of HGCA. Conclusions can help clinicians precisely evaluate the recurrence risk of patients, take the initiative to master the diagnosis and treatment, and increase the long-term survival rate of patients.

Effects of different surgical strategies and left ventricular remodelling on the outcomes of coronary artery bypass grafting in heart failure patients with reduced ejection fraction.

Ischaemic heart failure with reduced ejection fraction (HFrEF) caused by coronary artery disease accounts for the largest proportion of heart failure cases with the worst prognosis. Coronary artery bypass grafting (CABG) is the most effective treatment for ischaemic HFrEF. On-pump and off-pump are the two surgical methods used for CABG. Whether patients with HFrEF should undergo on- or off-pump CABG is controversial in coronary heart disease surgery. The left ventricular end-systolic volume index (LVSEVI) is the gold standard for evaluating the severity of left ventricular remodelling; however, its effect on the perioperative risk and long-term survival rate of patients with HFrEF undergoing CABG remains unclear. This single centre prospective cohort analysis included 118 coronary heart disease patients with symptoms and signs of heart failure and a left ventricular ejection fraction (LVEF) of <40% who were enrolled consecutively from January 2019 to December 2023. Operative mortality, perioperative complications, and long-term survival were compared among patients treated with various LVESVIs and surgical methods. The primary outcomes were cardiac death, myocardial infarction, heart failure, stroke, and revascularization, (percutaneous coronary intervention or redo CABG) with a median follow-up of 38 ± 10 months. The 30-day postoperative mortality of 118 patients was 6.8%. Patients in the off-pump group had significantly higher perioperative mortality than those in the on-pump group (12.5% vs. 3.8%, p = 0.03). In the off-pump group, a higher proportion of patients required perioperative mechanical assistance, such as intra-aortic artery balloon pump (IABP) or extracorporeal membrane oxygenation (ECMO), compared to those in the on-pump group (IABP: 75% vs. 47.4%, p = 0.004; ECMO: 22.5% vs. 1.3%, p = 0.000). Patients in the off-pump group were more likely to have postoperative atrial fibrillation (AF) (35% vs. 14.1%, p = 0.01). In the on-pump group, the incidence of postoperative AF (25% vs. 6.5%, p = 0.02) and IABP use (62.5% vs. 36.9%, p = 0.03) were significantly higher in patients with more severe left ventricular remodelling than in those with less severe left ventricular remodelling. In the off-pump group, patients with more severe left ventricular remodelling had higher ECMO usage (38.9% vs. 9.1%, p = 0.04), incidence of postoperative AF (61.1% vs. 13.6%, p = 0.02), and perioperative mortality (22.2%). Major adverse cardiac event (MACE)-free survival rate was significantly higher in the on-pump group than in the off-pump group, and there was no significant difference in MACE free survival rates between the two groups of patients with different degrees of left ventricular remodelling. On-pump bypass is a better surgical procedure for patients with ischaemic HFrEF, especially those with severe left ventricular remodelling. Left ventricular remodelling increases perioperative mortality but has no effect on long-term survival.

Levels of cardiac biomarkers and three-year survival rate in hospitalized patients with heart failure and community-acquired pneumonia

Aim. To evaluate the impact of community-acquired pneumonia (CAP) on the levels of cardiac biomarkers and long-term survival rate in patients with heart failure (HF).Material and methods. The prospective observational single-center study included 132 patients (73 men, 59 women); mean age — 72,3±12,1 years, consecutively hospitalized at Clinical Hospital № 4 of the I. M. Sechenov First Moscow State Medical University with decompensated heart failure in the period from March 2018 to December 2019. The main (n=40) and comparison group (n=92) included patients with and without clinical and CT signs of CAP, respectively.Results. Patients with HF and CAP and HF without CAP were comparable in sex, age, and severity of HF. CAP in most patients met the criteria for non-severe pneumonia (average CURB-65 score — 1,55±0,73). The levels of N-terminal probrain natriuretic peptide (NT-proBNP) in patients with HF with CAP (1188,9 [439; 2493] pg/ml) were insignificantly higher than in patients with HF without CAP (839,6 [413; 1900]) pg/ml (p&gt;0,05). A similar pattern was noted for the soluble growth stimulation expressed gene 2 (sST2) (30,85 [12,8; 59,6] ng/ml vs 22,8 [15,2; 44,7] ng/ml, p&gt;0,05). The haptoglobin level in patients with CAP was significantly lower (732 [315; 1312] ng/l), compared to the group without CAP (1270 [902; 2022] ng/l, p=0,0022). No differences in the concentrations of galectin-3, copeptin and hepcidin were detected. The one-year mortality rate of patients who underwent CAP was 27,3%, and without CAP — 7,2% (p&lt;0,001), while the three-year mortality rate was 44,9% and 21,4%, respectively (p=0,0004). Elevated levels of NT-proBNP and sST2, along with age over 75 years and left ventricular ejection fraction &lt;40%, are additional factors of poor prognosis in patients with HF and CAP.Conclusion. CAP in patients with HF does not have a significant effect on most cardiac biomarkers, but significantly worsens the prognosis. Independent factors of unfavorable prognosis in patients with HF and CAP are age over 75 years, left ventricular ejection fraction &lt;40%, increased NT-proBNP and sST2 levels.

Research Progress of the Combating Drug Resistance in Cancer Immunotherapy

Cancer drug resistance is one of the reasons why cancer remains one of the deadliest diseases. Many drugs show initial efficacy in treatment but fail to exert their effects due to various mechanisms, which is particularly evident in immunotherapy. Currently, research is ongoing on anti-resistance drugs that target immune suppression, mutations, and the tumor microenvironment (TME). However, the current immunotherapy approaches have not yielded satisfactory results, with most patients developing long-term resistance or the drugs themselves not being ideal for clinical use. This article reviews the causes of resistance and common immunotherapies along with their associated anti-resistance strategies. It is found that the clinical efficacy of anti-resistance drugs and long-term survival rates for patients are not ideal. Future research should focus on improving individual and cooperative effects of cytokine therapy, CAR-T cell therapy, ICI, and combination therapies to avoid the development of secondary resistance. The role of cytotoxicity, as one of the most significant treatment barriers, should also be investigated. Many anti-resistance drugs are limited in their use due to the damage they cause to normal cell survival and metabolism.

Abstract 2176: Differences in gut microbial composition alter pancreatic tumorigenesis

Abstract Pancreatic ductal adenocarcinoma (PDAC) is predicted to become the second leading cause of cancer-related deaths by 2030, and currently has a 5-year survival rate of roughly 10%. With long-term survival rates in patients being exceedingly low, understanding what factors delineate survival is imperative. When comparing spontaneous transgenic mouse models of pancreatic cancer housed in geographically distinct vivaria, regardless of a common lineage, we observed drastically different phenotype states in the respective locations. We hypothesize that the gut microbiome results in different gene expression profiles, leading to alterations in pancreatic tumorigenesis. Using various sequencing techniques, including 16s rRNA and RNA sequencing of the gut, we identified unique signatures at these respective institutions. Subsequent fecal microbiota transplantation and single bacterial species colonization experiments were performed to evaluate the ability of microbiomes/specific microbiota to alter the rate of tumorigenesis. In addition to probing the gut microbiome, circulating metabolites from individual mice were quantified, and correlated to phenotype state. Following identification of potentially tumorigenic bacterially derived metabolites, single bacteria colonization experiments were utilized to determine the downstream effects of identified metabolites as well as the ability of directly altering the metabolic landscape to drive tumorigenesis. Additionally, murine derived pancreatic cancer cells were exposed to both identified bacteria alone or bacterially produced metabolite and analyzed by metrics such as proliferation and relative expression of transcription factors associated with cancer development in vitro. Taken together, these data demonstrate the ability of distinct gut microbiomes to directly alter the metabolic landscape in mice, thus differentially altering the progression of pancreatic lesions. By better understanding the factors that stratify survivorship, we can begin to employ clinically actionable methodologies in the treatment or prevention of pancreatic cancer. Citation Format: Rian M. Howell, Jose Enriquez Ortiz, Olivia Le Roux, Vidhi Chandra, Le Li, Pratip K. Bhattacharya, Florencia McAllister. Differences in gut microbial composition alter pancreatic tumorigenesis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2176.

Enhancing COVID-19 Detection: An Xception-Based Model with Advanced Transfer Learning from X-ray Thorax Images.

Rapid and precise identification of Coronavirus Disease 2019 (COVID-19) is pivotal for effective patient care, comprehending the pandemic's trajectory, and enhancing long-term patient survival rates. Despite numerous recent endeavors in medical imaging, many convolutional neural network-based models grapple with the expressiveness problem and overfitting, and the training process of these models is always resource-intensive. This paper presents an innovative approach employing Xception, augmented with cutting-edge transfer learning techniques to forecast COVID-19 from X-ray thorax images. Our experimental findings demonstrate that the proposed model surpasses the predictive accuracy of established models in the domain, including Xception, VGG-16, and ResNet. This research marks a significant stride toward enhancing COVID-19 detection through a sophisticated and high-performing imaging model.

Early postoperative constrictive pericarditis in China: a single-center retrospective observational study.

The diagnosis, treatment, and prognosis of early postoperative constrictive pericarditis (EPCP) have not been discussed in depth. The objective of this study was to devise and propose a management strategy for EPCP. In this study, constrictive pericarditis (CP) within 6 months after cardiac surgery was defined as EPCP, and patients were divided into two groups based on intraoperative findings: a parietal thickening group and a visceral thickening group. A total of 20 patients were included in this study, and the incidence rate of recurrent pericardiectomy was 0.32% among all patients undergoing cardiovascular surgery. EPCP after valve surgery occurred in 85.0% of patients. Pleural effusion was the most common preoperative symptom, occurring in 90% of patients. Pericardial thickening occurred in the visceral layer in seven cases and in the parietal layer in 13 cases. There were no differences in comorbidities, C-reactive protein (CRP) level, or erythrocyte sedimentation rate (ESR) between the two groups. Most patients with visceral thickening (83.3%) needed cardiopulmonary bypass (CPB) assistance during surgery and had a longer hospital stay than those with parietal thickening (52.8±21.8 vs. 34.9±13.8 days, P=0.049). Central venous pressure (CVP) was decreased in all patients after pericardiectomy (24.9±6.96 vs. 8.9±2.92 cmH2O, P<0.001), and the cardiac function improved significantly in patients with parietal thickening [New York Heart Association (NYHA) grade ≥ III accounted for 28.6% of patients]. The long-term survival rate of patients with parietal thickening was 92.3% and that of patients with visceral thickening was 57.1%, and there was no significant difference between them (P=0.056). Recurrent episodes of chest tightness, pleural effusion, and elevated CVP within 6 months after cardiac surgery should be considered highly suggestive of EPCP. There are few points of difference between pericarditis with thickening of the parietal and visceral layers. After failure of conservative medical treatment, pericardiectomy results in significant improvements in cardiac function and quality of life, especially in patients with thickening of the parietal layer.

Comparable Outcomes of Relapsed Acute Lymphoblastic Leukemia in Adolescents and Young Adults (AYA) Patients Treated with Pediatric-Inspired Chemotherapy (R3 protocol) Versus Adult-Based Salvage (FA) Protocol

Background Although the survival rate of adolescents and young adults (AYA) with acute lymphoblastic leukemia (ALL) has improved by using pediatric-based treatment protocols, those who experience a relapse still have poor outcomes when treated with adult chemotherapy salvage-regimens, which have traditionally included high doses of Ara-C. The long-term survival rate for patients treated with these salvage-regimens is less than 10%. Salvage treatment with blinatumomab for adults with relapsed B-cell ALL results in a complete remission (CR) rate of 34%, a median survival of 7.7 months, and an overall survival (OS) of less than 30% at 18 months. In contrast, the ALLR3 protocol for relapsed ALL in patients up to the age of 18 years achieved a CR rate of 97% and an overall survival rate of 72%. Therefore, this study aims to compare the outcomes of AYA patients treated with pediatric-inspired regimen (R3 regimen) to those treated with adult-based regimen (FA (Fludarabine/Cytarabine) protocol). Methods The R3 protocol treated 17 AYA patients with relapsed Philadelphia-negative ALL, aged between 14 to 40 years old, who had received first-line therapy. Patients who achieved CR underwent allogenic transplant. The protocol included vincristine, mitoxantrone, asparaginase, dexamethasone, and intrathecal methotrexate. In comparison, 60 patients were treated with FA protocol, with patients achieved CR proceeded to allogeneic stem cell transplantation. Relapses were classified as very early (&amp;lt; 18 months from diagnosis), early (&amp;gt;18 months from diagnosis and &amp;lt;6 months from the end of therapy), and late (&amp;gt;6 months from the end of therapy). Patients' characteristics, response rate (RR) and overall survival (OS) were analyzed. Results The two arms had comparable characteristics. The median age in the R3 arm was 16 years (range: 14-40 years) compared to 22 years (range: 18-32 years) in the FA protocol arm. In the R3 arm, 88.2% of patients had B-cell ALL, while in the FA protocol arm, 92.2% had B-cell ALL. CNS involvement was seen in 28.8% and 17.6% of cases in the R3 and FA protocol arms, respectively. Relapses were classified as very early, early, or late in 2 (12%), 5 (29%), and 7 (41%) of cases in the R3 arm and were mostly late (25.2%) in the FA protocol arm. Relapses in the R3 arm were isolated bone marrow (BM), isolated extramedullary (EMD), or combined BM and EMD in 14 (82%), 1 (6%), and 2 (12%) cases, respectively, while EMD was around three times higher (16.9%) in the FA arm. The overall CR rate was 60% at the end of R3 induction, with negative MRD (&amp;lt;10 −4 cells) in 47.1% of patients. The overall CR rate was higher in the FA arm (76.3%), but the difference with the R3 arm was not statistically significant (p-value 0.1). The disease was refractory to subsequent salvage therapy in 42% of cases in both arms. About half of the patients who responded to R3 proceeded to allogeneic stem cell transplant (52.3%), while 78% of the patients post-FA underwent transplantation. Eight patients died (47%) in R3 arm, but only one patient died due to treatment-related sepsis, while the other seven patients died due to disease-related causes. At a median follow-up of 4 years, OS was 53% in the R3 arm compared to 30.8% in the FA arm, but the difference was not significant (p-value=0.8). The post-FA mortality was mainly due to infections (15.3% in FA vs. 5.9% in R3). Conclusion Pediatric-inspired protocols that have shown significant benefits in the front-line setting for ALL in the AYA population did not demonstrate a significant difference when compared to traditional adult-based salvage chemotherapy regimens in relapsed disease.

Abstract 18441: Long-Term Outcomes of Total Arch Replacement With Frozen Elephant Trunk Procedure for Patients With Acute Type A Aortic Dissection: A Single-Center Experience

Introduction: Total arch replacement (TAR) with frozen elephant trunk (FET) is an extensive surgical procedure for patients with acute type A aortic dissection (ATAAD). This study aimed to investigate the long-term outcomes of TAR with FET procedure for patients with ATAAD. Methods: A total of 670 patients with ATAAD who underwent TAR with FET procedure between January 2013 and December 2018 were included in this study. The patients were divided into two groups: the early group (n=245, 2013-2015) and the modern group (n=425, 2016-2018). In-hospital and long-term outcomes were compared between the two groups. Results: The average age and gender distribution were similar between the two groups (P&gt;0.05). The modern group had a higher prevalence of preoperative coma (P&lt;0.001). Patients in the modern group had a shorter mean duration of surgical procedure, including cardiopulmonary bypass time (189.8 ± 53.0 vs 176.0 ± 53.0 min, P=0.001) and hypothetical cardiac arrest time (22.8 ± 5.2 vs 15.1 ± 6.2 min, P&lt;0.001). Although the in-hospital mortality was lower in the modern group, the difference was not statistically significant (6.1% vs 3.3%, P=0.064). The modern group had a significantly lower incidence of postoperative major adverse outcomes compared to the early group (33.9% vs 20.2%, P&lt;0.001). The mean follow-up period was similar between the two groups. The overall long-term survival rate of patients undergoing TAR with FET procedure in this cohort was 92.7%. Patients in the modern group had a significantly lower cumulative incidence of all-cause mortality compared to those in the early group (P&lt;0.001). Cox regression analysis showed that the modern year was an independent protective factor for the long-term survival of ATAAD patients undergoing TAR with FET procedure (HR=0.336, 95% CI: 0.193-0.585, P&lt;0.001). Conclusions: The in-hospital and long-term outcomes of TAR with FET procedure for patients with ATAAD are promising and have improved over time.

Clinical analysis of long-term survival and influencing factors of chimeric antigen receptor T-cell therapy in relapsed/refractory acute B-cell lymphoblastic leukemia

Objective: To analyze the survival and influencing factors of chimeric antigen receptor (CAR) T-cell therapy in relapsed/refractory acute B-cell lymphoblastic leukemia (R/R B-ALL) . Methods: Clinical information of patients who received CAR-T-cell therapy and achieved complete remission of R/R B-ALL between May 2015 and June 2018 at the Shaanxi Provincial People's Hospital was obtained. Kaplan-Meier analysis was used to evaluate the overall survival (OS) and leukemia-free survival (LFS) times of patients, and Cox regression analysis was performed to analyze the prognostic factors that affect patient survival after CAR-T therapy. Results: Among the 38 patients with R/R B-ALL, 21 were men, with a median age of 25 (6-59) years and a median OS time of 18 (95% CI 3-33) months. Multivariate Cox regression analysis showed that positive MLL-AF4 fusion gene expression was an independent risk factor for OS and LFS (OS: HR=4.888, 95% CI 1.375-17.374, P=0.014; LFS: HR=6.683, 95% CI 1.815-24.608, P=0.004). Maintenance therapy was a protective factor for OS and LFS (OS: HR=0.153, 95% CI 0.054-0.432, P<0.001; LFS: HR=0.138, 95% CI 0.050-0.382, P<0.001). In patients with MRD negative conversion, LFS benefit (HR=0.209, 95% CI 0.055-0.797, P=0.022) and OS difference was statistically insignificant (P=0.111). Moreover, patients with high tumor burden were risk factors for OS and LFS at the level of 0.1 (OS: HR=2.662, 95% CI 0.987-7.184, P=0.053; LFS: HR=2.452, 95% CI 0.949-6.339, P=0.064) . Conclusion: High tumor burden and high-risk genetics may affect the long-term survival rate of patients with R/R B-ALL receiving CAR-T, and lenalidomide-based maintenance therapy may improve their prognosis.