Long-term Survival Rate Of Patients Research Articles

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.

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 posttransplant mortality. The present study is to explore the outcomes and risk factors of early bacterial infection (within 1mo) 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 posttransplant 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 posttransplant 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- and 5-year survival rates for recipients with posttransplant 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 multi-drug 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 posttransplant 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 posttransplant infection rate, albeit without statistical significance (adjusted RR, 0.53; 95% CI, 0.25-1.16). In this cohort study, posttransplant bacterial infection resulted in an inferior long-term patient survival rate. The five identified independent risk factors for posttransplant bacterial infection could guide the prophylaxis strategy of posttransplant bacterial infection in the future. Additionally, pretransplant RSC might decrease posttransplant bacterial infection rate.

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.

413. 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.

Mitochondria in cancer stem cells: Achilles heel or hard armor.

Previous studies have shown that mitochondria play core roles in not only cancer stem cell (CSC) metabolism but also the regulation of CSC stemness maintenance and differentiation, which are key regulators of cancer progression and therapeutic resistance. Therefore, an in-depth study of the regulatory mechanism of mitochondria in CSCs is expected to provide a new target for cancer therapy. This article mainly introduces the roles played by mitochondria and related mechanisms in CSC stemness maintenance, metabolic transformation, and chemoresistance. The discussion mainly focuses on the following aspects: mitochondrial morphological structure, subcellular localization, mitochondrial DNA, mitochondrial metabolism, and mitophagy. The manuscript also describes the recent clinical research progress on mitochondria-targeted drugs and discusses the basic principles of their targeted strategies. Indeed, an understanding of the application of mitochondria in the regulation of CSCs will promote the development of novel CSC-targeted strategies, thereby significantly improving the long-term survival rate of patients with cancer.

Systematic evaluation of the safety and therapeutic effects of para-aortic lymphadenectomy for advanced gastric cancer: a systematic review and meta-analysis.

At present, there is still no definite conclusion on whether advanced gastric cancer (GC) requires additional para-aortic nodes dissection (PAND). The purpose of this study is to summarize current evidence on the potential benefits of the extended systemic lymphadenectomy (D2+) compared to D2 lymphadenectomy in the treatment of gastric cancer. Systematic literature search was performed across PubMed, Embase, Cochrane library, Web of Science, China National Knowledge Infrastructure, Wanfang Data Knowledge Service Platform, VIP Database for Chinese Technical Periodicals, and China Biology Medicine disc using the following terms: gastric cancer, para-aortic lymphadenectomy, D2+ lymphadenectomy and D3 lymphadenectomy. RevMan 5.3 software was used for the meta-analysis. A total of 20 studies involving 5,643 patients were included, consisting of 6 randomized controlled trials (RCT) and 14 non-randomized controlled trials (nRCT). Compared with the D2 group, the operating time in the D2+ group was longer [mean difference (MD)=99.45 min, 95% confidence interval (CI) (48.93, 149.97), p<0.001], with more intra-operative blood loss [MD=262.14 mL, 95% CI (165.21, 359.07), p<0.001]. There were no significant differences in five-year overall survival (OS) [HR=1.09, 95% CI (0.95, 1.25), p=0.22] and post-operative mortality [RR=0.96, 95% CI (0.59, 1.57), p=0.88] between the two groups. The rate of post-operative complications in group D2+ was higher than that in group D2 [RR=1.42, 95% CI (1.11, 1.81), p<0.001]. Prophylactic D2+ surgery is not recommended, since D2+ surgery is associated with an increased rate of post-operative complications and does not improve the long-term survival rate of patients with advanced gastric cancer. However, D2+ surgery (especially D2+PAND) has certain survival advantages for specific patients, and D2+PAND surgery combined with chemotherapy may potentially improve long-term survival rate.

Transjugular Intrahepatic Portosystemic Shunt Benefits for Hepatic Sinusoidal Obstruction Syndrome Associated with Consumption of Gynura Segetum: a Propensity Score-Matched Analysis.

Pyrrolidine alkaloids-related hepatic sinusoidal obstruction syndrome (PA-HSOS) is associated with a high mortality rate without standardized therapy. The efficacy of transjugular intrahepatic portosystemic shunts (TIPS) remains controversial. The study aimed to explore the risk factors influencing the clinical response in patients with PA-HSOS related to Gynura segetum (GS) to assess the disease prognosis at an early stage and to evaluate the efficacy of TIPS in these patients. This study retrospectively enrolled patients diagnosed with PA-HSOS between January 2014 and June 2021 with a clear history of exposure to GS. Univariate and multivariate logistic regression analyses were used to evaluate the risk factors influencing the clinical response in patients with PA-HSOS. Propensity score matched (PSM) was performed to compensate for differences in baseline characteristics between patients with and without TIPS. The primary outcome was the clinical response defined as the disappearance of ascites with normal total bilirubin levels and/or a reduction of elevated transaminase levels < 50% within 2weeks. A total of 67 patients were identified in our cohort with a clinical response rate of 58.2%. Of these, thirteen patients were assigned to the TIPS group and 54 to the conservative treatment group. Logistic regression analysis revealed that TIPS treatment (P = 0.047), serum globulin levels (P = 0.043), and prothrombin time (P = 0.001) were independent factors influencing clinical response. After PSM, there was a higher long-term survival rate of patients (92.3% vs. 51.3%, P = 0.021) and a shorter hospital stay (P = 0.043), but a high trend in hospital costs (P = 0.070) in the TIPS group. The 6-month survival probability in patients undergoing TIPS therapy was more than ninefold higher than in patients without receiving that treatment [hazard ratio (95% CI) = 9.304 (4.250, 13.262), P < 0.05]. TIPS therapy may be an effective treatment option for patients with GS-related PA-HSOS.

Efficacy and safety of biological agents for pemphigoid: asystematic review and meta-analysis.

Biologic agents (also termed biologics) have become an important adjuvant-targeted treatment option in autoimmune blistering disease. We evaluated the efficacy and safety of newly licensed biologics for the management of pemphigoid using a meta-analysis. PubMed, EMBASE, Web of Science, and the Cochrane Library for studies involving pemphigoid patients treated with biological agents (rituximab, dupilumab, omalizumab, or mepolizumab) were searched. The pooled risk ratio (RR) with a 95% confidence interval (CI) was used to assess the short-term efficacy, adverse event (AE), relapse, and long-term survival. A total of seven studies involving 296 patients were identified. The pooled RRs for short-term effectiveness, AE, relapse, and long-term survival rate in patients treated with biological agents versus systemic corticosteroids were 1.37 (95% CI 0.95-1.97; I2 = 82%; P = 0.09), 0.54 (95% CI 0.39-0.73; I2 = 13%; P = 0.005), 1.36 (95% CI 0.95-1.96; I2 = 16.8%; P = 0.19), and 1.08 (95% CI 0.95-1.21; I2 = 48.1%; P = 0.53), respectively. Meta-regression and subgroup analysis revealed that the RRs of efficacy were 2.10 (95% CI 1.61-2.75; I2 = 0%; P < 0.00001) for rituximab and 2.07 (95% CI 1.61-2.67; I2 = 0%; P < 0.00001) for sample size greater than 30. Compared with conventional therapy, biologics treatment was significantly associated with fewer adverse events (P < 0.05), but no significant differences were found for efficacy and relapse (P > 0.05). The findings demonstrate that a biologics-containing regimen could minimize the occurrence of AEs and might display a comparable efficacy and recurrence to that of receiving systemic corticosteroids.

The Role of Multidimensional Indices for Mortality Prediction in Chronic Obstructive Pulmonary Disease

(1) Background: Chronic obstructive pulmonary disease (COPD) is one of the most important respiratory diseases. It is characterised by a progressive course with individual differences in clinical presentation and prognosis. The use of multidimensional indices such as the BODE, eBODE, BODEX, CODEX, ADO, and Charlson Comorbidity Index has been proposed to predict the survival rate of COPD patients. However, there is limited research on the prognostic significance of these indices in predicting long-term survival rates in patients with COPD. The aim of this prospective cohort study was to investigate the prognostic value of the BODE, eBODE, BODEX, CODEX, ADO, COTE and Charlson Comorbidity Index in predicting 5- and 10-year survival in patients with COPD. (2) Methods: A total of 170 patients were included in the study and their clinical and functional characteristics of COPD progression, such as dyspnoea, body mass index and spirometry data, were evaluated. A Kaplan-Meier survival analysis was used to calculate 5- and 10-year survival rates. The predictive value of each index was assessed using Cox proportional hazards regression models. (3) Results: The 5-year survival rate was 62.35% and the 10-year survival rate was 34.70%. The BODE, eBODE, BODEX, CODEX, ADO, COTE and Charlson Comorbidity Index were all significantly associated with the 10-year survival rate of COPD patients (p < 0.05). The hazard ratios (HRs) for these indices were as follows: BODE (HR = 1.30, 95% confidence interval [CI] 1.21-1.39); eBODE (HR = 1.29, 95% CI 1.21-1.37); BODEX (HR = 1.48, 95% CI 1.35-1.63); CODEX (HR = 1.42, 95% CI 1.31-1.54); COTE (HR = 1.55, 95% CI 1.36-1.75); ADO (HR = 1.41, 95% CI 1.29-1.54); and Charlson Comorbidity Index (HR = 1.35, 95% CI 1.22-1.48). (4) Conclusions: The multidimensional indices are a useful clinical tool for assessing the course and prognosis of COPD. These indices can be used to identify patients at a high risk of mortality and guide the management of COPD patients.

Allogeneic hematopoietic stem cell transplantation in acute leukemia patients with the SET-NUP214 fusion gene: Efficacy and survival analysis

Objective: To investigate the clinical efficacy of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for patients with acute leukemia who are positive for the SET-NUP214 fusion gene (SET-NUP214+AL). Methods: This was a retrospective case series study. Clinical data of 18 patients with SET-NUP214+AL who received allo-HSCT in the First Affiliated Hospital of Soochow University and Soochow Hongci Hematology Hospital from December 2014 to October 2021 were retrospectively analyzed to investigate treatment efficacy and prognosis. The Kaplan-Meier method was used for survival analysis. Results: Of the 18 patients, 12 were male and 6 were female, and the median age was 29 years (range, 13-55 years). There were six cases of mixed phenotype acute leukemia (three cases of myeloid/T, two cases of B/T, one case of myeloid/B/T), nine cases of acute lymphoblastic leukemia (ALL) (one case of B-ALL and eight cases of T-ALL), and three cases of acute myeloid leukemia. All patients received induction chemotherapy after diagnosis, and 17 patients achieved complete remission (CR) after chemotherapy. All patients subsequently received allo-HSCT. Pre-transplantation status: 15 patients were in the first CR, 1 patient was in the second CR, 1 was in partial remission, and 1 patient did not reach CR. All patients were successfully implanted with stem cells. The median time of granulocyte and platelet reconstitution was +12 and +13 days, respectively. With a median follow-up of 23 (4-80) months, 15 patients survived, while 3 patients died. The cause of death was recurrence of SET-NUP214+AL after transplantation. After allo-HSCT, 5 patients relapsed. The estimated 3-year overall survival (OS) and relapse-free survival (RFS) rates were 83.3%±15.2% and 55.4%±20.7%, respectively. Among the 15 patients who achieved CR before transplantation, there was no significant difference in OS and RFS between haploidentical HSCT and matched sibling donor HSCT (all P>0.05). Conclusions: Allo-HSCT can improve the prognosis and long-term survival rate of patients with SET-NUP214+AL. Disease recurrence is the most important factor affecting long-term survival.

Long-term prognosis of patients with chronic heart failure and reduced left ventricular ejection fraction receiving cardiac contractility modulation therapy: the impact of comorbidity burden on outcomes

Aim . To investigate the association between comorbidity burden and long-term clinical outcomes of patients with reduced left ventricular ejection fraction (HFrEF) undergoing cardiac contractility modulation (CCM). Methods . Our study included 59 patients with HFrEF, functional class II/III (NYHA), sinus rhythm, who underwent implantation of CCM system between September 2015 and December 2018 and were further followed by a multidisciplinary team. A mean follow-up period was 1916±102 days. All-cause mortality and heart transplantation were considered as primary composite endpoint. The secondary composite endpoint included all-cause mortality, heart transplantation, im- plantable cardioverter defibrillator shocks due to ventricular tachyarrhythmia and hospitalizations due to decompensated HF. Predicted survival rate were calculated using MAGGIC Risk Calculator and Seattle Heart Failure Model (SHFM). Initially, the Charlson comorbidity index (CCI) was calculated for all patients. Results. Three- and five-year survival rates were 79,7% and 66,1%, respectively, which were significantly higher than predicted by MAGGIC (p=0.02) and SHFM (p=0.01). The median time to the primary endpoint was 1494 days and the annual mortality was 7%. Patients with HF NYHA class III, chronic kidney disease and CCI ≥7 points had worse prognosis (p 1 =0.002, p 2 =0.003, p 3 =0.04 (log-rank test). There was a significant decrease in number of hospitalized pa- tients due to HF decompensated during CCM (p˂0.001) compared with the six-month period before the system implantation. Patients with CCI value ≥ 7 points reached secondary composite endpoint faster (p=0.002 and p=0.004 for three-year and five-year follow-up periods, respectively (log-rank test)). Conclusion . Long-term survival rates of patients with HFrEF II/III (NYHA) receiving CCM and managed on multidisciplinary team were significantly higher than predicted. The heavy comorbidity burden negatively impacts on the clinical course and outcomes of HF patients following CСM implantation. Applying the Charlson index can be useful in a comprehensive assessment of the prognosis and determining the target population for the expensive implantable devices, including CCM, in risk stratification and decision-making algorithms.

Treatment of bilateral Wilms’ tumor in children: how to improve the application of nephron-sparing surgery

To summarize the experience of nephron-sparing surgery (NSS) for bilateral Wilms tumors (BWT) in children. This study included children with BWT admitted to our hospital between January 2008 and June 2022. The details of the treatments and outcomes were analyzed. In all, 70 patients (39 males and 31 females) were enrolled, including 66 patients with synchronous tumors and 4 patients with metachronous tumors. The median age at diagnosis was 13 (3-75) months. Overall, 59 patients received preoperative chemotherapy and 45.8% (54/118) of the 118 sides of WT achieved a partial response (PR). Of the 70 patients, 48 (68.6%) underwent bilateral NSS and 22 (31.4%) underwent unilateral NSS and contralateral total nephrectomy. The proportion of bilateral NSS in the preoperative chemotherapy group was significantly higher than in the non-chemotherapy group (P = 0.031). Additionally, there were 26, 25, 14, and 5 cases of stage I, stage II, stage III, and stage IV, respectively. Among the 70 children, 16 had a recurrence, and 8 died. The 4years EFS and OS were 67.9% and 89.3%, respectively. The long-term survival rates of patients with BWT improved. Hence, preoperative chemotherapy should be administered to enhance the use of NSS in BWT.

Clinical factors affecting the long-term survival of breast cancer patients.

The average 5-year survival rate of breast cancer (BC) patients has been significantly prolonged with new therapeutic methods. However, their effects on BC patient long-term survival rates are unclear. Therefore, this study aimed to analyze the specific clinical factors that can affect BC long-term survival. Here, we conducted a retrospective study and analyzed long-term survival using data of 3,240 BC patients from 1977 to 2005 from the Genotype-Tissue Expression (GTEx) database using the Kaplan-Meier method. Breast tumor size and stage were negatively correlated with long-term survival, but age showed no significant correlation. Estrogen receptor (ER) and progesterone receptor (PR) expression were each positively correlated with patient survival time, while ERBB2 receptor (HER2) expression was negatively correlated with survival time. Patients with high Nottingham prognostic index (NPI) values did not benefit from available therapies. Furthermore, breast-conserving surgery is more conducive to BC patient long-term survival than mastectomy. Early detection and breast-conserving surgery may support long-term survival for BC patients. Elevated expression of ER and PR were both associated with longer patient survival time, while positive expression of HER2 showed the opposite trend. The long-term survival rates of patients with high NPI values can potentially be increased.

Family Knowledge, Attitudes, and Practices Toward Severe Congenital Neutropenia.

Severe congenital neutropenia is a rare disorder. The survival and quality of life of patients radically improved through infection prevention, use of granulocyte colony-stimulating factor, and the appropriate use of antibiotics during infections. The aim of this study was to evaluate the precautions taken by families to prevent infections, the level of knowledge regarding the disease, and the impact of external factors such as education and economic status on behavior and compliance in patients and caregivers in terms of the following treatment protocols. Questionnaires were designed with the aim of determining how the social, cultural, and economic conditions of the families of children with severe congenital neutropenia affected their behavior and knowledge levels. They were completed using one-on-one video interviews with the caregivers. Thirty-one patients from 25 families were enrolled into the study. No correlations between family disease knowledge, parent education levels, working status of the mother, sibling numbers, economic status, ease of hospital access, and/or residential location were found. An increase in disease knowledge of patients and caregivers, as well as proven approaches to living with the disease, would directly correlate to increased life quality and long-term survival rates of patients.