Lower Long-term Survival Research Articles

Endoscopic Imaging for the Diagnosis of Neoplastic and Pre-Neoplastic Conditions of the Stomach.

Gastric cancer is an aggressive disease with low long-term survival rates. An early diagnosis is essential to offer a better prognosis and curative treatment. Upper gastrointestinal endoscopy is the main tool for the screening and diagnosis of patients with gastric pre-neoplastic conditions and early lesions. Image-enhanced techniques such as conventional chromoendoscopy, virtual chromoendoscopy, magnifying imaging, and artificial intelligence improve the diagnosis and the characterization of early neoplastic lesions. In this review, we provide a summary of the currently available recommendations for the screening, surveillance, and diagnosis of gastric cancer, focusing on novel endoscopy imaging technologies.

Total Anomalous Pulmonary Venous Connection: Surgical Outcomes and Risk Factors for Postoperative Pulmonary Vein Obstruction.

Total anomalous pulmonary venous connection (TAPVC) is a fatal congenital cardiac anomaly that requires urgent surgical intervention. The development of postoperative pulmonary vein obstruction (PVO) negatively impacts long-term survival. The present study aimed to evaluate the surgical outcomes of TAPVC repair and risk factors associated with postoperative PVO. Patients who underwent primary TAPVC repair at our institute between 2004 and 2022 were retrospectively enrolled, and those with right atrial isomerism and single ventricle physiology were excluded. Factors associated with survival and postoperative PVO were analyzed. A total of 116 patients were enrolled in the present study. The early mortality rate was 6.9%. Nineteen patients (16.4%) developed postoperative PVO within a median time of 59 days of the primary repair, of whom 10 were successfully relieved without any recurrent obstruction. In long-term follow-up, patients with postoperative PVO had significantly lower long-term survival rates than those without postoperative PVO [57.9%, 95% confidence interval (CI) = 34.8-79.5%; vs. 90.4%, 95% CI = 83-96.6% at 10 years, p < 0.001]. Risk factors for postoperative PVO development included lower body weight, younger age, preoperative mechanical ventilation, preoperative inotrope use, and emergency operation. Postoperative PVO was significantly associated with a higher long-term mortality rate after primary TAPVC repair, with the risk being higher in patients with critical preoperative status. The long-term outcome was good for patients in whom the obstruction was successfully relieved. Early detection and prompt intervention for postoperative PVO after TAPVC repair can improve overall survival in these patients.

Mechanism of Action of Decitabine in the Treatment of Acute Myeloid Leukemia by Regulating LINC00599.

Acute myeloid leukemia (AML) is a heterogeneous malignancy with a low long-term survival rate. The aim of this study was to investigate the effects of decitabine (DAC) treatment cell proliferation and apoptosis in AML and role of the expression of LINC00599 and, consequently, miR-135a-5p. Human promyelocytic leukemia cells (HL-60) and human acute lymphatic leukemia (CCRF-CEM) cells were treated with various concentrations of DAC. Cell proliferation in each group was detected using the cell counting kit 8. For each group, apoptosis and reactive oxygen species (ROS) levels were detected using flow cytometry. Reverse transcription polymerase chain reaction (RT-PCR) was performed to examine the expression of lncRNA LINC00599. The expression of apoptosis-related proteins was analyzed using western blotting. The regulatory relationship between miR-135a-5p and LINC00599 was verified by constructing miR-135a-5p mimics, miR-135a-5p inhibit, wild type LINC00599 3'-untranslated region (UTR), and mutant LINC00599 3'-UTR. Ki-67 expression in the tumor tissues of nude mice was detected using immunofluorescent assays. Both DAC and LINC00599 Inhibit groups were able to significantly reduce the proliferation of HL60 and CCRF-CEM cells, increase apoptosis, upregulate the expression of Bad, cleaved caspase-3, and miR-135a-5p, downregulate the expression of Bcl-2, and elevate ROS levels in cells, with these effects being more pronounced after combined treatment with DAC and LINC00599 Inhibit. In comparison to mimic NC, the miR-135a-5p mimic group significantly decreased the relative fluorescence activity ratio of LINC00599 3'-UTR wild-type CCRF-CEM cells. The LINC00599 Inhibit and miR-135a-5p mimic groups exhibited substantially reduced proliferation of HL60 and CCRF-CEM cells, increased apoptosis, upregulated Bad, cleaved caspase-3, and miR-135a-5p expression, along with downregulated Bcl-2 and LINC00599 expression and increased ROS levels in cells; these effects were more pronounced after LINC00599 Inhibit was combined with miR-135a-5p mimics. In vivo experiments revealed that both DAC and LINC00599 Inhibit were able to considerably reduce the long diameter, short meridian, volume, and mass of tumors, increase miR-135a-5p expression, and decrease LINC00599 and ki-67 expression in tumor tissues of nude mice. This effect was more pronounced when the DAC and LINC00599 Inhibit were used in combination. DAC regulates the expression of miR-135a-5p by regulating the expression of LINC00599, which in turn affects cell proliferation, apoptosis, and tumor proliferation. Our findings provide a theoretical basis for improving the clinical outcome of AML.

Sonodynamic Therapy for the Treatment of Glioblastoma Multiforme in a Mouse Model Using a Portable Benchtop Focused Ultrasound System.

Sonodynamic therapy (SDT) is an application of focused ultrasound (FUS) that enables a sonosensitizing agent to prime tumors for increased sensitivity during sonication. Unfortunately, current clinical treatments for glioblastoma (GBM) are lacking, leading to low long-term survival rates among patients. SDT is a promising method for treating GBM in an effective, noninvasive, and tumor-specific manner. Sonosensitizers preferentially enter tumor cells compared to the surrounding brain parenchyma. The application of FUS in the presence of a sonosensitizing agent generates reactive oxidative species resulting in apoptosis. Although this therapy has been shown previously to be effective in preclinical studies, there is a lack of established standardized parameters. Standardized methods are necessary to optimize this therapeutic strategy for preclinical and clinical use. In this paper, we detail the protocol to perform SDT in a preclinical GBM rodent model using magnetic resonance-guided FUS (MRgFUS). MRgFUS is an important feature of this protocol, as it allows for specific targeting of a brain tumor without the need for invasive surgeries (e.g., craniotomy). The benchtop device used here can focus on a specific location in three dimensions by clicking on a target on an MRI image, making target selection a straightforward process. This protocol will provide researchers with a standardized preclinical method for MRgFUS SDT, with the added flexibility to change and optimize parameters for translational research.

Recent Advances on Surface-Modified GBM Targeted Nanoparticles: Targeting Strategies and Surface Characterization.

Glioblastoma multiforme (GBM) is the most common malignant brain tumor, associated with low long-term survival. Nanoparticles (NPs) developed against GBM are a promising strategy to improve current therapies, by enhancing the brain delivery of active molecules and reducing off-target effects. In particular, NPs hold high potential for the targeted delivery of chemotherapeutics both across the blood-brain barrier (BBB) and specifically to GBM cell receptors, pathways, or the tumor microenvironment (TME). In this review, the most recent strategies to deliver drugs to GBM are explored. The main focus is on how surface functionalizations are essential for BBB crossing and for tumor specific targeting. We give a critical analysis of the various ligand-based approaches that have been used to target specific cancer cell receptors and the TME, or to interfere with the signaling pathways of GBM. Despite the increasing application of NPs in the clinical setting, new methods for ligand and surface characterization are needed to optimize the synthesis, as well as to predict their in vivo behavior. An expert opinion is given on the future of this research and what is still missing to create and characterize a functional NP system for improved GBM targeting.

Tumor burden score dictates prognosis of patients with combined hepatocellular cholangiocarcinoma undergoing hepatectomy.

The prognostic value of the tumor burden score (TBS) in patients with combined hepatocellular-cholangiocarcinoma (cHCC-CCA) remains unknown. This study aimed to investigate the impact of TBS on long-term outcomes after surgery. Patients who underwent radical-intent resection between June 2013 and December 2019 were retrospectively reviewed. Kaplan-Meier curves were used to analyze patient survival, and disease-free survival (DFS) and overall survival (OS) were examined in relation to TBS. A total of 178 patients were included in this study, with 119 in the training cohort and 59 in the validation cohort. Kaplan-Meier curves showed that TBS was a strong prognostic indicator in patients with cHCC-CCA. Elevated TBS was associated with poorer DFS and OS (both P-value < 0.001) and was identified as an independent prognostic indicator. In addition, the prognostic value of TBS outperformed tumor size and number alone, microvascular invasion, and lymph node invasion. The prognostic significance of TBS was confirmed by the internal validation cohort. The present study suggested the significance of tumor morphology in assessing the prognosis of patients with cHCC-CCA who undergoing curative resection. The TBS is a promising prognostic index in patients with cHCC-CCA. Elevated TBS was related to a lower long-term survival rate and was identified as an independent risk factor for poor DFS and OS. Further research is needed to verify our results.

Phenological response to climate variation in a northern red oak plantation: Links to survival and productivity.

In a changing climate, the future survival and productivity of species rely on individual populations to respond to shifting environmental conditions. Many tree species, including northern red oak (Quercus rubra), exhibit phenotypic plasticity, the ability to respond to changes in environmental conditions at within-generation time scales, through varying traits such as leaf phenology. Phenotypic plasticity of phenology may vary among populations within a species' range, and it is unclear if the range of plasticity is adequate to promote fitness. Here, we used a 58-year-old common garden to test whether northern red oak populations differed in phenological sensitivity to changes in temperature and whether differences in phenological sensitivity were associated with differences in productivity and survival (proxies of fitness). We recorded 8 years of spring leaf emergence and autumn leaf coloration and loss in 28 distinct populations from across the species' full range. Across the 28 populations, spring leaf out consistently advanced in warmer years, but fall phenology was less responsive to changes in temperature. Southern, warm-adapted populations had larger shifts in phenology in response to springtime warming but had lower long-term survival. Moreover, higher phenological sensitivity to spring warming was not strongly linked to increased productivity. Instead, fitness was more closely linked to latitudinal gradients. Although springtime phenological sensitivity to climate change is common across northern red oak populations, responses of productivity and survival, which could determine longer-term trajectories of species abundance, are more variable across the species' range.

Surgical Treatment of Constrictive Pericarditis.

The mainstay of the treatment of constrictive pericarditis is pericardiectomy. However, surgery is associated with high early morbidity and mortality and low long-term survival. The aim of this study is to describe our series of pericardiectomies performed over 30 years. A descriptive, observational, and retrospective analysis of all pericardiectomies performed at the Institute of Cardiology and Cardiovascular Surgery of the Favaloro Foundation was performed. A total of 45 patients underwent pericardiectomy between June 1992 and June 2022, mean age was 52 years (standard deviation ± 13.9 years), and 73.3% were men. Idiopathic constrictive pericarditis was the most prevalent (46.6%). The variables significantly associated with prolonged hospitalization were preoperative advanced functional class (incidence of 38.4%, P<0.04), persistent pleural effusion (incidence of 81.8%, P<0.01), and although there was no statistical significance with the use of cardiopulmonary bypass, a trend in this association is evident (P<0.07). We found that 100% of the patients with an onset of symptoms greater than six months had a prolonged hospital stay. In-hospital mortality was 6.6%, and 30-day mortality was 8.8%. The preserved functional class is 17 times more likely to improve their symptomatology after pericardiectomy (odds ratio 17, 95% confidence interval 2.66-71; P<0.05). Advanced functional class at the time of pericardiectomy is the variable most strongly associated with mortality and prolonged hospitalization. Onset of the symptoms greater than six months is also a poor prognostic factor mainly associated with prolonged hospitalization; based on these data, we strongly support the recommendation of early intervention.

Surgical management for elderly patients with pancreatic cancer.

Pancreatic cancer, one of the diseases of the elderly, has dismal prognosis, demanding major surgery with high risk and life quality problems, especially in the elderly. Therefore, treatment selection, whether or not to undergo surgery, preoperative risk assessment, and perioperative management of the elderly are becoming critical issues. Although the elderly are expected to have higher morbidity and mortality and lower long-term survival outcomes, surgery is becoming safer over time. Appropriate surgical indication selection, patient-centered decision-making, adequate prehabilitation and postoperative geriatric care are expected to improve surgical outcomes in the elderly. Surgeons must have the concept of geriatric care, and efforts based on institutional systems and academic societies are required. If well selected and prepared, the same surgical principle as non-elderly patients can be applied to elderly patients. In this paper, the surgical treatment of elderly patients with pancreatic cancer is reviewed.

High expression of B4GALT1 is associated with poor prognosis in acute myeloid leukemia.

Acute myeloid leukemia is the most prevalent type of leukemia in adults and is prone to relapse and chemoresistance, with a low long-term survival rate. Therefore, the identification of quality biomarkers constitutes an urgent unmet need. High expression of beta-1,4-galactosyltransferase 1 (B4GALT1) has been observed in several cancer types; however, its function in acute myeloid leukemia has rarely been studied. Therefore, our study obtained gene expression data from The Cancer Genome Atlas (TCGA) database to analyze the relationship between B4GALT1 and LAML. We compared the expression of B4GALT1 in LAML and healthy samples using the Wilcoxon rank-sum test. Furthermore, the association between B4GALT1 and survival rates was investigated using Kaplan-Meier analysis and Cox regression. The nomogram obtained by Cox analysis predicts the effect of B4GALT1 on the prognosis. To assess B4GALT1-related genes' enrichment pathway and function and the correlation between B4GALT1 and immune features, GO/KEGG, protein-protein interaction network, and single sample gene set enrichment analysis were used. In addition, B4GALT1-specific siRNAs were used to verify the effect of B4GALT1 on apoptosis. The results showed that B4GALT1 is overexpressed in LAML and has some reference value in the diagnostic and prognostic assessment of LAML. Moreover, functional enrichment showed that B4GALT1 and its 63 associated genes were closely associated with the negative regulation of the apoptotic signaling pathway. Silencing B4GALT1 significantly promoted apoptosis. In addition, B4GALT1 expression was positively correlated with the infiltration levels of macrophages, regulatory T-cell (Tregs), and Th17 cells; in contrast, B4GALT1 expression was negatively correlated with the infiltration levels of T helper cells, Mast cells, and NK cells. In conclusion, our study shows that B4GALT1 may play a vital role in the occurrence of LAML.

MAGOH and MAGOHB Knockdown in Melanoma Cells Decreases Nonsense-Mediated Decay Activity and Promotes Apoptosis via Upregulation of GADD45A

Cutaneous malignant melanoma is a highly proliferative and aggressive skin cancer with a steadily increasing incidence and a low long-term survival rate after metastatic progression. The protein MAGOH and its highly identical homologue MAGOHB are core components of the exon junction complex (EJC), which regulates splicing, stability and translation of mRNAs. The EJC, and especially MAGOH, has been shown to be involved in the development and progression of several cancers. In melanoma, the expression and function of both homologues remain essentially unexplored. This study identifies high MAGOH and MAGOHB protein expression in cutaneous melanoma cell lines and patient derived tissue samples. An siRNA-mediated knockdown of MAGOH significantly inhibits melanoma cell proliferation. The loss of MAGOH does not affect cell cycle progression, but induces apoptosis, an effect that is enhanced by a simultaneous knockdown of MAGOH and MAGOHB. MAGOH and MAGOHB do not influence the expression of the pro-apoptotic protein Bcl-XS or exon skipping. However, the knockdown of MAGOH and MAGOHB strongly decreases nonsense-mediated decay (NMD) activity, leading to an upregulation of the pro-apoptotic protein GADD45A. In conclusion, simultaneous inhibition of MAGOH and MAGOHB expression substantially affects cell survival, indicating both MAGOH homologues as promising new targets for the treatment of melanoma.

Phase 1b Trial of Subcutaneous Epcoritamab in Pediatric Patients with Relapsed or Refractory (R/R) Aggressive Mature B-Cell Neoplasms (EPCORE Peds-1)

Background: Burkitt lymphoma and diffuse large B-cell lymphoma (DLBCL) are the most common types of mature B-cell lymphoma (MBL) in children. A majority (90%-95%) of children with these malignancies are cured with initial chemoimmunotherapy (CIT), leaving a small portion of patients with relapsed or refractory (R/R) disease who have a poor prognosis (Cairo et al, J Clin Oncol 2012). R/R MBL is often treated with aggressive CIT regimens such as R-VICI or R-ICE, but a high, unmet need remains (Woessmann et al, Blood 2020). Long-term survival is observed in approximately 20% to 30% of pediatric cases of R/R MBL, with better long-term survival seen in those who attain complete response (CR) with reinduction CIT and reach consolidation with stem cell therapy. Patients with partial response (PR) after reinduction CIT may undergo stem cell transplant but typically have lower long-term survival rates than those experiencing CR (Burkhardt et al, Cancers 2021). Long-term survival or cure in patients with R/R MBL requires an effective therapy that results in CR before stem cell transplant. Epcoritamab is a bispecific antibody that binds CD3 on T cells and CD20 on B cells, inducing potent and selective T-cell-mediated killing of malignant CD20+ B cells. The phase 1/2 EPCORE NHL-1 study (NCT03625037) of epcoritamab monotherapy in adult patients with R/R B-cell non-Hodgkin lymphoma established the recommended phase 2 dose (RP2D) and demonstrated safety and promising efficacy, including deep and durable responses (overall response rate [ORR], 63%; CR rate, 39%; preliminary median duration of response [DOR], 12 months) in a population with highly refractory large B-cell lymphoma (n=157) (Thieblemont et al, EHA 2022). Because favorable safety and efficacy data were observed in adults, it is reasonable to investigate use of epcoritamab in children with R/R MBL who fail to achieve CR with reinduction CIT or are unable to receive further consolidation with stem cell therapy after CIT. Study Design and Methods: EPCORE Peds-1 is a single-arm, open-label, phase 1b study (NCT05206357) evaluating the safety, pharmacokinetics, pharmacodynamics preliminary efficacy, and immunogenicity of epcoritamab monotherapy in pediatric and young adult patients with R/R Burkitt lymphoma, Burkitt-like lymphoma/leukemia, DLBCL, or other aggressive CD20+ MBL. Primary endpoints are safety and tolerability, including incidence and severity of cytokine release syndrome, immune cell-associated neurotoxicity syndrome, and clinical tumor lysis syndrome, as well as pharmacokinetic parameters of maximum observed concentration and area under the concentration-time curve from time 0 to last measurable concentration within the dosing interval. Secondary endpoints include CR per International Pediatric Non-Hodgkin Lymphoma response criteria, event-free survival, overall survival, initiation of stem cell transplant/chimeric antigen receptor T-cell therapy, ORR, DOR, duration of CR, and immunogenicity. Exploratory endpoints include the monitoring of pharmacodynamic markers such as cytokines and immunophenotyping of B and T cells. At least 15 patients will be enrolled with a maximum age of 25 years (for those with Burkitt lymphoma), with at least 12 patients 1 year of age or older but younger than 18 years who are evaluable for primary endpoint assessment. Eligibility criteria require that patients have not reached remission with reinduction CIT or are ineligible for further consolidation with cell therapy and have acceptable performance status (Lansky, Karnofsky, or Eastern Cooperative Oncology Group, depending on age). Epcoritamab will be subcutaneously administered using step-up dosing (priming and intermediate doses on days 1 and 8 of cycle 1 [28 days/cycle], followed by 10 weekly full doses from day 15 of cycle 1 through cycle 3; Figure). Additional full doses will be administered every 2 weeks for cycles 4 to 9 and every 4 weeks for cycles 10 and beyond for a maximum of 2 years of treatment. Epcoritamab priming-, intermediate-, and full-dose regimens will be based on weight categories; patients weighing at least 40 kg will receive the adult RP2D. Disease status will be assessed by CT/MRI/PET prior to epcoritamab administration on day 1 and at a minimum at weeks 6, 12, 24, 36, and 48 and at 18 and 24 months. Patients will be followed for at least 3 years after enrollment. Enrollment is ongoing in North America, Asia, Europe, and Australia. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Red Blood Cell Membrane-Camouflaged Gold Nanoparticles for Treatment of Melanoma.

Background Patients with melanoma have poor response and low long-term survival to conventional cisplatin (CP). Recently, biomimetic nanoparticles have played a significant role in tumor therapy. The purpose of this study was to mechanistically evaluate the effect of red blood cell membrane camouflaged gold nanoparticles loaded with CP (RBCm@AuNPs-CP) on enhancing chemotherapy in melanoma. Methods Treated B16-F10 cells with RBCm@AuNPs-CP, the antimelanoma effect in vitro was explored by detecting cell viability, apoptosis rate, level of reactive oxygen species (ROS), and singlet oxygen. RBCm@AuNPs-CP was injected into the melanoma-bearing mice via tail vein, and the target-ability, therapeutic effect, and toxicity were detected in melanoma tumor-bearing mice. Results RBCm@AuNPs-CP had an antiproliferation and apoptosis-inducing effect on B16-F10 cells, which might be mediated by oxidative stress of ROS, and its effect was significantly enhanced compared with the CP treatment group. In vivo experiments suggested the same outcome, with better target-ability of RBCm@AuNPs-CP. Conclusion The erythrocyte camouflage nanosystem RBCm@AuNPs-CP exhibited well passive tumor target-ability and promoted apoptosis of melanocytes by inducing ROS. RBCm@AuNPs-CP as a novel safe and effective targeted drug delivery system may provide a promising choice for the treatment of melanoma.

Associations between DAPT score and long-term mortality post PCI

Abstract Introduction The dual antiplatelet therapy (DAPT) score was developed to identify patients more likely to derive benefit (score ≥2) or harm (score &amp;lt;2) from DAPT beyond 1-year post PCI. There is no study which looked at the DAPT score and long term outcomes post PCI in Australia. Purpose We sought to examine long-term mortality after PCI by the DAPT score in patients treated with DAPT per local guidelines. Methods We examined data from the MIG PCI database from 2005 to 2018 in whom the DAPT score could be derived and grouped them as score ≥2 or &amp;lt;2. Long-term mortality was assessed from National Death Index linkage. The primary endpoint was long-term mortality examined using survival analysis. Secondary endpoints included 30-day ischaemic outcomes and in-hospital major bleeding. Results Out of 27,740 patients in the study, 9,401 (33.9%) had DAPT score ≥2. They were younger and included more females and higher prevalence of renal impairment. DAPT score ≥2 patients had higher in-hospital major bleeding, 30-day mortality, MI and target vessel revascularisation. DAPT score ≥2 patients had lower long-term survival to 12 years (p&amp;lt;0.001 for all). Conclusion A third of all-comer PCI patients had DAPT score ≥2 with greater short-term risk of ischaemic and bleeding outcomes, as well as long-term mortality. Theoretically, those with DAPT score ≥2 would benefit from longer duration of DAPT as ischaemic risk outweighs bleeding risk. However, given our finding of increased short-term bleeding risk and long-term mortality, dynamic bleeding risk assessment should be undertaken to guide pharmacotherapy strategies. Funding Acknowledgement Type of funding sources: None.

Prediction of one-year adverse clinical outcomes by macrophage migration inhibitory factor in stemi patients

Biomarkers have taken one of the first places as diagnostic and prognostic tools in ST-segment elevation myocardial infarction (STEMI) and are consequently widely used as predictors of short-term and long-term prognosis. One of the promising biomarkers for early cardiovascular outcomes prediction is the pro-inflammatory cytokine macrophage migration inhibitory factor (MIF).&#x0D; The aim of the study was to elucidate a plausible predictive value of the MIF levels for one-year clinical outcomes in STEMI patients who underwent primary percutaneous coronary intervention (PCI).&#x0D; Materials and methods. 134 STEMI patients were enrolled in the study after receiving voluntary informed consent. All patients underwent conventional investigations, and additionally, the MIF levels were determined at baseline, directly before and after PCI. During 1-year follow-up, 37 % of patients reached the endpoint, which was composite and included all-cause mortality, non-fatal myocardial infarction, non-fatal stroke, hospitalization for unstable angina, heart failure decompensation, and urgent revascularization.&#x0D; Results. We have found that pre-PCI MIF levels &gt; 3934 pg/mL (AUC=0.7; 95 % CI 0.578 to 0.753; Youden index=0.31; p=0.008) might be an independent predictor of composite endpoints with sensitivity 54 % and specificity 82 %. A positive correlation between MIF and inflammatory biomarkers was revealed (WBC count r=0.33, p=0.0001; CRP r=0.19, p=0.032). Adverse outcomes associated with higher pre- and post-PCI MIF levels (OR 1.0, 95 % CI 1.0001–1.0008; p=0.013 and OR 1.0, 95 % CI 1.0001–1.0009; p=0.019) and CRP that determined during the first week after the event (OR 1.0, 95 % CI 1.005–1.2, p=0.03). Kaplan-Meier analysis has shown a substantially lower long-term survival rate in patients with a MIF level &gt; 3493 pg/ml compared to a MIF level ≤ 3493 pg/ml (Log rank=0.00025).&#x0D; Conclusions. The MIF levels exceeding 3934 ng/ml were associated with a higher risk of one-year adverse clinical outcomes in STEMI patients who underwent primary PCI.

Long-term outcome prediction for chronic thromboembolic pulmonary hypertension after pulmonary endarterectomy.

The definitive treatment for chronic thromboembolic pulmonary hypertension (CTEPH) is pulmonary endarterectomy (PEA), which has good long-term outcomes. However, after surgery, a quarter of the patients still have residual pulmonary hypertension (RPH). In pulmonary hemodynamics, there are no unified criteria for RPH, even though the level may affect long-term survival. Between March 1997 and December 2021, 253 CTEPH patients were treated at our center with PEA. Patients were evaluated retrospectively and classified into early (1997-2014) and late (2015-2021) groups. The clinical characteristics and perioperative outcomes of the two groups were compared, and risk factor analysis for RPH and long-term survival for all cases was performed. There was no statistically significant difference in demographics between the two groups. However, the Early Group had a significantly higher rate of perioperative death (9.8% vs. 1.2%, p = .001), RPH (48.8% vs. 14.0%, p < .001), and reperfusion pulmonary edema (18.3% vs. 2.9%, p < .001). The median follow-up time was 66.0 months, and overall survival rates at 5, 10, 15, and 18 years after PEA were 91.2%, 83.9%, 64.5%, and 46.0%, respectively. Age and postoperative systolic pulmonary artery pressure (sPAP) were independently related to long-term outcomes in the multivariate Cox analyses. Patients with postoperative sPAP less than 46 mm Hg had a higher chance of survival. PEA improved CTEPH hemodynamics immediately and had a positive effect on long-term survival. Patients with postoperative sPAP ≥ 46 mm Hg indicate clinically significant RPH and have a lower long-term survival rate.

Risk factors associated with 10-year survival after coronary artery bypass grafting

Coronary artery bypass grafting (CABG) is the treatment of choice for a broad spectrum of patients with coronary disease. To describe global survival and factors associated with lower long-term survival in patients operated with isolated CABG. Analysis of a cohort of patients who underwent CABG between January 2006 and December 2008 at a public hospital. The database and operation records of 1.003 cardiac surgeries were reviewed. Of these, an isolated CABG was performed in 658 patients aged 62 ± 9 years including 516 male (78%). Survival data were obtained from the Chilean Civil Registry Office and a complete ten-year follow up was accomplished. Survival was analyzed with Kaplan-Meier method with log-rank test and Cox regression. Operative mortality occurred in 13 patients (2%). Survival at 1, 3, 5 and 10 years was 97, 94, 91 and 76%, respectively. One, 3, 5 and 10-year free of cardiovascular death survival was 98, 97, 95 y 89%, respectively. Factors associated with long-term survival were chronic kidney disease in hemodialysis (Hazard ratio (HR) 7.9; 95% confidence intervals (CI) 4.6-13.6), chronic obstructive pulmonary disease (HR 2.3; 95% CI 1.4-3.7), chronic arterial occlusive disease (HR 2.2; 95% CI 1.4-3.4) and diabetes mellitus (HR 1.9; 95% CI 1.4-2.6). According to EuroSCORE, 10-year survival was 86, 75 and 62% (p < 0.01) in low, medium and high-risk patients, respectively. These patients had a 10-year survival comparable to large international series. Groups associated with lower 10-year survival were identified.

MiR-29b Regulates Lung Cancer Progression by Downregulating FEM1B and Inhibiting the FOX01/AKT Pathway.

Purpose Lung cancer is a relatively common type of cancer, and the incidence rate has been on the rise in recent years. MicroRNAs are a class of endogenous small RNA molecules, which are essential for the posttranscriptional regulation of genes. miR-29b is closely related to the occurrence and development of tumors, including prostate cancer, colon cancer, and breast cancer. However, few studies have been performed to explore the expression and pathway of miR-29b in non-small-cell lung cancer (NSCLC). Methods Using bioinformatics analysis, we found that patients with low relative expression of the miR-29b gene have a low long-term survival rate. The results of in vitro research showed that when miR-29b expression was upregulated, the invasion, migration, and proliferation of A549 and NCI-H-1792 cells was inhibited, and the apoptosis was accelerated. Results The results showed that FEM1B is a miR-29b target gene, and the expressions of FEM1B and miR-29b were negatively correlated. Like the upregulation of miR-29b expression, silencing the FEM1B expression could also impair the invasion, migration, and proliferation abilities of A549 and NCI-H-1792 cells. When FEM1B expression was restored, the inhibitory effect of miR-29b could be reversed. Reverse transcription-polymerase chain reaction (RT-PCR) and western blot (WB) analysis showed that overexpression of miR-29b could inhibit the expression of FEM1B, AKT, vascular endothelial growth factor (VEGF), and Sirt3 in A549 and NCI-H-1792 cells and upregulate the expression of FOXO1 protein. Conclusion The results of this study indicate that miR-29b inhibits the proliferation and deterioration of NSCLC cells by targeting FEM1B and inhibiting the activation of the FOXO1/AKT pathway. miR-29b may become a new target for the clinical diagnosis and treatment of lung cancer, and it is expected to become a new inhibitor of NSCLC.

Predictors of mortality after atrial correction of transposition of the great arteries

ObjectivesTo determine the long-term and transplantation-free survival of all patients after atrial correction of transposition of the great arteries (TGA) in the Czech and Slovak republics, including its preoperative and...

Association of Frailty, Organ Support, and Long-Term Survival in Critically Ill Patients With COVID-19.

OBJECTIVES:Few studies have explored the effect of frailty on the long-term survival of COVID-19 patients after ICU admission. Furthermore, the Clinical Frailty Scale (CFS) validity in critical care patients remains debated. We investigated the association between frailty and 6-month survival in critically ill COVID-19 patients. We also explored whether ICU resource utilization varied according to frailty status and examined the concurrent validity of the CFS in this setting.DESIGN:Ancillary study of a longitudinal prospective cohort.SETTING:University hospital in São Paulo.PATIENTS:Patients with severe COVID-19 admitted to ICU.INTERVENTIONS:None.MEASUREMENTS AND MAIN RESULTS:We assessed baseline frailty using the CFS (1–9; frail ≥ 5) and used validated procedures to compute a Frailty Index (0–1; frail > 0.25). We used Cox models to estimate associations of frailty status with 6-month survival after ICU admission and area under the receiver operating characteristic curves (AUCs) to estimate CFS’s accuracy in identifying frailty according to Frailty Index. We included 1,028 patients (mean age, 66 yr; male, 61%). Overall, 224 (22%) patients were frail (CFS ≥ 5), and 608 (59%) died over the 6-month follow-up. Frailty was independently associated with lower 6-month survival and further stratified mortality in patients with similar age and Sequential Organ Failure Assessment scores. We additionally verified that the CFS was highly accurate in identifying frailty as defined by the Frailty Index (AUC, 0.91; 95% CI, 0.89–0.93). Although treatment modalities did not diverge according to frailty status, higher CFS scores were associated with withholding organ support due to refractory organ failure.CONCLUSIONS:One in five COVID-19 patients admitted to the ICU was frail. CFS scores greater than or equal to 5 were associated with lower long-term survival and decisions on withholding further escalation of invasive support for multiple organ failure in the ICU. Clinicians should consider frailty alongside sociodemographic and clinical measures to have a fuller picture of COVID-19 prognosis in critical care.