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Journal of Clinical Orthopaedics and... Jun 2024Traumatic cervical spine injury is common among spinal cord injury which requires an intensive, multidisciplinary approach which can affect the immediate postoperative...
BACKGROUND
Traumatic cervical spine injury is common among spinal cord injury which requires an intensive, multidisciplinary approach which can affect the immediate postoperative hospital survival rate. By identifying the risk factors leading to early mortality in cervical spine trauma patients, the prognosis of patients with TCSCI can be better predicted.
OBJECTIVE
The study aims to analyze the variables influencing in-hospital mortality in cervical spine trauma patients treated at a Level I trauma Center.
METHODS
Prospective study was conducted on subaxial cervical spine injuries from July 2019 to March 2022. Patients were divided into two groups: Group A, with in-hospital mortality, and Group B, who got discharged from hospital, and mortality predictors were reviewed and analyzed for as potential risk factors for in-hospital mortality.
RESULTS
Out of 105 patients, 83.8 % were male with mean age of 40.43 ± 12.62 years. On univariate analysis, AIS (p-value: <0.01), ICU stay (p-value: <0.01), level of injury (p-value: <0.01), and MRI parameters like the extent of Parenchymal damage (p-value: <0.01), MSCC (p-value: <0.01), and MCC (p-value: <0.01) were potential risk factors for in-hospital mortality. On multivariate regression analysis AIS at presentation (p-value: 0.02) was the only significant independent parameter for in-hospital mortality.
CONCLUSIONS
AIS grading at presentation, duration of ICU stay, level of injury, rate of tracheostomy, and MRI parameters like the extent of parenchymal damage, MCC, and MSCC influence and predicts in-hospital mortality, whereas AIS is the only independent risk factor.
PubMed: 38947859
DOI: 10.1016/j.jcot.2024.102440 -
Kidney Medicine Jul 2024The option for A2/A2B deceased donor kidney transplantation was integrated into the kidney allocation system in 2014 to improve access for B blood group waitlist...
RATIONALE & OBJECTIVE
The option for A2/A2B deceased donor kidney transplantation was integrated into the kidney allocation system in 2014 to improve access for B blood group waitlist candidates. Despite excellent reported outcomes, center uptake has remained low across the United States. Here, we examined the effect of implementing an A2/A2B protocol using a cutoff titer of ≤1:8 for IgG and ≤1:16 for IgM on blood group B kidney transplant recipients at a single center.
STUDY DESIGN
Retrospective observational study.
SETTING & PARTICIPANTS
Blood group B recipients of deceased donor kidney transplants at a single center from January 1, 2019, to December 2022.
EXPOSURE
Recipients of deceased donor kidney transplants were analyzed based on donor blood type with comparisons of A2/A2B versus blood group compatible.
OUTCOMES
One-year patient survival, death-censored allograft function, primary nonfunction, delayed graft function, allograft function as measured using serum creatinine levels and estimated glomerular filtration rate at 1 year, biopsy-proven rejection, and need for plasmapheresis.
ANALYTICAL APPROACH
Comparison between the A2/A2B and compatible groups were performed using the Fisher test or the χ test for categorical variables and the nonparametric Wilcoxon rank-sum test for continuous variables.
RESULTS
A total of 104 blood type B patients received a deceased donor kidney transplant at our center during the study period, 49 (47.1%) of whom received an A2/A2B transplant. Waiting time was lower in A2/A2B recipients compared with blood group compatible recipients (57.9 months vs 74.7 months, = 0.01). A2/A2B recipients were more likely to receive a donor after cardiac death (24.5% vs 1.8%, < 0.05) and experience delayed graft function (65.3% vs 41.8%). There were no observed differences in the average serum creatinine level or estimated glomerular filtration rate at 1 month, 3 months, and 1 year post kidney transplantation, acute rejection, or primary nonfunction.
LIMITATIONS
Single-center study. Small cohort size limiting outcome analysis.
CONCLUSIONS
Implementation of an A2/A2B protocol increased transplant volumes of blood group B waitlisted patients by 83.6% and decreased the waiting time for transplantation by 22.5% with similar transplant outcomes.
PubMed: 38947773
DOI: 10.1016/j.xkme.2024.100843 -
Endoscopic Ultrasound 2024To compare the efficacy of EUS-guided celiac plexus neurolysis (CPN) and celiac plexus irradiation with iodine-125 (I) seeds with absolute ethanol for relieving pain in...
Clinical efficacy of EUS-guided celiac plexus neurolysis EUS-guided celiac ganglion irradiation with iodine-125 seeds for pain relief in advanced pancreatic cancer: A long-term retrospective study.
BACKGROUND AND OBJECTIVE
To compare the efficacy of EUS-guided celiac plexus neurolysis (CPN) and celiac plexus irradiation with iodine-125 (I) seeds with absolute ethanol for relieving pain in patients with advanced pancreatic cancer.
METHODS
We retrospectively analyzed data of 81 patients with advanced pancreatic cancer who underwent EUS-CPN or EUS-I implantation between January 2017 and December 2020. Postoperative pain was assessed using visual analog scale (VAS) scores; self-assessments of quality of life and the median survival time were compared between the 2 groups.
RESULTS
EUS-CPN and I implantation were performed in 43 and 38 patients, respectively. Postoperative VAS scores were significantly lower than the preoperative levels in both groups. One week after the operation, 26 patients (60.5%) in the EUS-CPN group achieved partial pain relief, whereas no patients in the EUS-I seed group experienced pain relief. However, after 4 weeks postoperatively, VAS scores had decreased, and the rate of partial pain relief was higher for EUS-I seeds than for EUS-CPN. Self-assessments of quality of life were similar in both groups during the first 1 month after the procedure.
CONCLUSIONS
Both EUS-CPN and EUS-I seeds can safely and effectively relieve pain in patients with advanced pancreatic cancer. Although EUS-I seeds take additional time to show effects, the extent and duration of pain relief are better compared with CPN, and interestingly, the median survival time was different.
PubMed: 38947749
DOI: 10.1097/eus.0000000000000048 -
Cureus May 2024Cervical cancer is the fourth most common cause of malignant tumor-related deaths among women in developing nations. Cervical cancer has been estimated to cause 527.600...
Feasibility and Diagnostic Accuracy of Ultrastaging in the Detection of Micrometastases in Sentinel and Non-sentinel Lymph Nodes in Cervical Cancer: A Single-Center Retrospective Study With a Five-Year Follow-Up Period.
BACKGROUND
Cervical cancer is the fourth most common cause of malignant tumor-related deaths among women in developing nations. Cervical cancer has been estimated to cause 527.600 new cases and 265.700 deaths globally per year.
OBJECTIVES
This study aimed to evaluate patients with cervical cancer by ultrastaging all the lymph nodes (LN), sentinel LN (SLN) and non-SLN, to increase the sensitivity of the detection of LN metastases and the diagnostic accuracy in cervical cancer with a five-year follow-up.
MATERIALS AND METHODS
This is a retrospective study of 14 cervical cancer cases from 2017 to 2019 at the Municipal Emergency Clinical Hospital of Timisoara, Romania. The cases were selected based on their high risk of LN involvement but negative intraoperative pathologic LN. After re-evaluating all paraffin block biopsy samples from 29 cases, 14 cases were included in the study, which met all criteria for ultrastaging on surgical biopsy samples.
RESULTS
Patients' ages included in the study ranged from 43 to 70 years (median: 57.14 years). According to the International Federation of Gynecology and Obstetrics (FIGO) staging, the majority of the patients were in stage IB: seven cases (50%). The study revealed a positive correlation between patient age and FIGO staging, with Pearson's correlation coefficient of 0.707 and a p-value of less than 0.05, indicating that older patients were more likely to be diagnosed with a higher FIGO stage. The mean follow-up was 34.5 months, and the median follow-up was 36 months (range: 6-60 months). We obtained 167 nodes, with a mean of 11.92 nodes/case. Twenty-one LN were found to be positive with the ultrastaging method. We detected 11 LN with macrometastases (MAC) (52.38%), seven with micrometastasis (MIC) (33.3%), and three with tumor cell islets (14.4%). That would be 13% of newly diagnosed ultrastaging cases as positive nodes. This ultrastaging method detected nodal MIC in eight (57.1%) out of the 14 patients, who initially tested negative for LN involvement using the routine Hematoxylin and Eosin (HE) method. The detection of micrometastases in these patients underscored the superior sensitivity of ultrastaging, which was further highlighted by the subsequent relapse of four (28.57%) out of these eight patients. The study also found no correlation between the FIGO standardization and the number of MIC found in these patients.
CONCLUSIONS
Predicting cervical LN metastasis (LNM) is crucial for improving survival rates and reducing recurrence. Very few small cohort studies used an ultrastaging method to assess non-SLNs; most of them only assessed SLNs. We showed in our study that the ultrastaging method, both in the case of SLN and non-SLN, is superior compared with H&E analysis, with a 13% rate of new positive nodule diagnosis. Metastatic involvement of non-SLN was found in over 50% of all cases (8/14) according to the ultrastaging method. Additionally, our study confirms that the sensitivity of SLN ultrastaging is high for the presence of both MIC and MAC in SLN pelvic LN. As a result, we feel that ultrastaging is the most effective method for SLN analysis in patients with early-stage cervical cancer, and bilateral detection is preferable, significantly reducing false-negative results. The routine use of SLN along with ultrastaging would lead to more accurate surgical staging and better oncological follow-up of cases.
PubMed: 38947581
DOI: 10.7759/cureus.61336 -
Heliyon Jun 2024Non-small cell lung Cancer (NSCLC) persists as a lethal neoplastic manifestation, exhibiting a diminished 5-year survival rate, partially attributable to...
BACKGROUND
Non-small cell lung Cancer (NSCLC) persists as a lethal neoplastic manifestation, exhibiting a diminished 5-year survival rate, partially attributable to chemotherapeutic resistance. This investigative endeavor aimed to elucidate the synergistic antineoplastic effects and underlying mechanisms of the SMYD2 inhibitor BAY-598 and the chemotherapeutic agent doxorubicin (DOX) in NSCLC.
METHODS
The human non-small cell lung cancer cell lines A549 and H460 were subjected to treatment regimens involving BAY-598 and/or DOX. Cellular viability, apoptotic events, invasive capacity, and migratory potential were evaluated through the implementation of CCK-8 assays, flow cytometric analyses, and Transwell assays, respectively. Protein expression levels were quantified via Western blot analyses. An in vivo xenograft murine model was established to assess therapeutic efficacy.
RESULTS
BAY-598 and DOX synergistically suppressed the viability, invasiveness, and migratory capabilities of NSCLC cells. Co-treatment Promoting cell apoptosis and cell cycle arrest. Additionally, Furthermore, co-administration significantly inhibited cell migration and invasion. Mechanistic studies revealed coordinately inhibited JAK-STAT signaling upon combination treatment. In vivo study further validated the synergistic antitumor efficacy of BAY-598 and DOX against NSCLC xenografts.
CONCLUSIONS
Our findings demonstrate that BAY-598 potentiates the anti-cancer effects of DOX in non-small cell lung cancer cells by modulating the JAK/STAT signaling pathway as a synergistic strategy. The combination holds promise as an emerging therapeutic strategy for NSCLC. Further optimization and validation are warranted to promote its translational potential.
PubMed: 38947456
DOI: 10.1016/j.heliyon.2024.e32015 -
Heliyon Jun 2024This work aimed to investigate the adoption value of blood lactic acid (BLA) combined with the National Early Warning Score (NEWS) in the early screening of sepsis...
This work aimed to investigate the adoption value of blood lactic acid (BLA) combined with the National Early Warning Score (NEWS) in the early screening of sepsis patients and assessing their severity. The data and materials utilized in this work were obtained from the electronic medical record system of 537 anonymized sepsis patients who received emergency rescue in the emergency rescue area of Liuzhou People's Hospital, Guangxi, from July 1, 2020, to December 26, 2020. Based on the 28-day outcomes of sepsis patients, the medical records were rolled into Group S (407 survival cases) and Group D (130 dead cases). Basic information such as the mode of hospital admission, initial management, use of emergency ventilator within 24 h of admission, NEWS score, arterial oxygen pressure/alveolar oxygen pressure ratio (PaO/PAO), alveolar-arterial oxygen difference (A-aDO), serum creatinine (SCr), blood urea nitrogen (BUN), oxygenation index (OI), Glasgow Coma Scale (GCS), D-dimer, use of vasoactive drugs within 24 h of admission, C-reactive protein (CRP), procalcitonin (PCT), interleukin-6 (IL-6), N-terminal pro-B-type natriuretic peptide (NT-proBNP), quick Sequential Organ Failure Assessment (qSOFA) score, SOFA score, BLA level, NEWS with lactate (NEWS-L) score, SOFA score including lactate level (SOFA-L) score, Intensive Care Unit (ICU) length of stay, total hospital stay, ICU stay/total hospital stay, and septic shock condition were compared between groups. Logistic regression analysis was performed to assess the impact of various predictive factors on prognosis and to plot the receiver operating characteristic (ROC) curve. The results suggested marked differences between Group S and Group D in terms of mean age ( = -5.620; OR = -9.96, 95 % CI: -13.44∼-6.47; < 0.001). Group S showed drastic differences in terms of mode of hospital admission (χ = 9.618, < 0.01), method of initial management (χ = 51.766, < 0.001), use of emergency ventilator within 24 h of admission (χ = 98.564, < 0.001), incidence of septic shock (χ = 77.545, < 0.001), use of vasoactive drugs within 24 h of admission (χ = 102.453, < 0.001), heart rate ( = -4.063, < 0.001), respiratory rate ( = -4.758, < 0.001), oxygenation status (χ = 20.547, < 0.001), NEWS score ( = -6.120, < 0.001), PaO/PAO ratio ( = 2.625, < 0.01), A-aDO value ( = -3.581, < 0.001), OI value ( = -3.106, < 0.01), PLT value ( = -2.305, < 0.05), SCr value ( = -3.510, < 0.001), BUN value ( = -3.170, < 0.01), D-dimer ( = -4.621, < 0.001), CRP level ( = -4.057, < 0.001), PCT value ( = -2.783, < 0.01), IL-6 level ( = -2.904, < 0.001), length of hospital stay ( = -4.138, < 0.001), total hospital stay ( = -8.488, < 0.001), CCU/total hospital stay ( = -9.118, < 0.001), NEWS score ( = -6.120, < 0.001), SOFA score ( = -6.961, < 0.001), SOFA-L score ( = -4.609, < 0.001), NEWS-L score ( = -5.845, < 0.001), BLA level ( = -6.557, < 0.001), and GCS score ( = 6.909, < 0.001) when compared to Group D. The use of ventilators, septic shock, PCT, NEWS score, GCS score, SOFA score, SOFA-L score, NEWS-L score, and BLA level were identified as independent risk factors for predicting the prognosis of sepsis patients ( < 0.001). The areas under ROC curve (AUC) of blood lactic acid, PCT, NEWS, NEWS-L, GCS, SOFA, and SOFA-L were 0.695, 0.665, 0.692, 0.698, 0.477, 0.700, and 0.653, respectively. These findings indicate that the combination of BLA with NEWS (NEWS-L) score and SOFA score has certain advantages in assessing the prognosis of sepsis.
PubMed: 38947447
DOI: 10.1016/j.heliyon.2024.e31907 -
ECT2 promotes the occurrence and is a prognostic biomarker of head and neck squamous cell carcinoma.Journal of Cancer 2024Epithelial Cell Transforming Sequence 2 (ECT2) has been implicated in various tumorigenic processes, including proliferation, migration, and invasion. However, its...
Epithelial Cell Transforming Sequence 2 (ECT2) has been implicated in various tumorigenic processes, including proliferation, migration, and invasion. However, its specific role in head and neck squamous cell carcinoma (HNSCC) remains unclear. This study integrates transcriptomic and single-cell RNA sequencing (scRNA-seq) data to explore the potential role of ECT2 in HNSCC. Differential expression analysis, cell-based assays (including CCK-8 for proliferation, transwell for migration, invasion assays, and flow cytometry for apoptosis and cell cycle analysis), and enrichment analysis were employed to investigate ECT2 expression levels and its regulatory effects on cellular phenotypes. Additionally, Mendelian randomization analysis was utilized to identify genes causally related to HNSCC using publicly available Genome-Wide Association Study (GWAS) data. ECT2 is highly expressed in HNSCC samples and its downregulation inhibits proliferation, migration, invasion, induces apoptosis, and affects the cell cycle transition in HSC-3 cells. Furthermore, differential analysis revealed significant differences in the immune microenvironment and drug sensitivity between high and low ECT2 expression groups. The pathways enriched in different groups include CCR and its related chemokines, as well as HLA in antigen presentation and immune response. There are also significant differences in the sensitivity to drugs such as bortezomib and dasatinib between the two groups. Prognostic models constructed from prognosis-related genes showed significant differences in prognosis between high and low-risk groups. Integration of scRNA-seq data identified Monocyte clusters as high-scoring cell clusters based on genes interacting with ECT2.Mendelian randomization analysis identified three genes (LGALS2, SLC11A1, and TKT) causally related to HNSCC within this cell cluster. Conclusion: The findings suggest that ECT2 overexpression is associated with the survival rate of HNSCC, indicating its potential as a prognostic biomarker for this malignancy.
PubMed: 38947403
DOI: 10.7150/jca.95515 -
Journal of Cancer 2024Bone cancer among adolescents and children exhibits varying survival outcomes based on disease state. While localized bone cancer cases have a survival rate exceeding... (Review)
Review
Bone cancer among adolescents and children exhibits varying survival outcomes based on disease state. While localized bone cancer cases have a survival rate exceeding 70%, metastatic, refractory, and recurrent forms are associated with significantly poorer prognoses. Initially believed to be mere vehicles for cellular waste disposal, exosomes are now recognized as extracellular vesicles facilitating intercellular communication. These vesicles influence cellular behaviors by transporting various biomolecules, such as proteins, DNA, RNA, and lipids, among cells. The role of exosomes in regulating the progression of bone cancer is increasingly evident, impacting critical processes like tumorigenesis, proliferation, metastasis, angiogenesis, immune evasion, and drug resistance. Current research underscores the substantial potential of exosomes in promoting the progression and development of bone cancer. This review delves into the complex process of exosome biogenesis, the variety of cell-derived exosome sources, and their applications in drug delivery and therapeutics. It also examines ongoing clinical trials focused on exosome cargo levels and discusses the challenges and future directions in exosome research. Unlike costly and invasive traditional diagnostic methods, exosomal biomarkers offer a non-invasive, cost-effective, and readily accessible routine screening through simple fluid collection that aims to inspire researchers to investigate the potential of exosomes for cancer theragnostic. Through comprehensive exploration of these areas, the review seeks to enhance understanding and foster innovative solutions to cancer biology in the near future.
PubMed: 38947401
DOI: 10.7150/jca.95709 -
Journal of Cancer 2024Pancreatic cancer continues to pose a significant threat due to its high mortality rate. While MYB family genes have been identified as oncogenes in certain cancer...
Pancreatic cancer continues to pose a significant threat due to its high mortality rate. While MYB family genes have been identified as oncogenes in certain cancer types, their role in pancreatic cancer remains largely unexplored. The mRNA and protein expression of MYB family genes in pancreatic cancer samples was analyzed using TNMplot, HPA, and TISBID online bioinformatics tools, sourced from the TCGA and GETx databases. The relationship between MYB family gene expression and survival time was assessed through Kaplan-Meier analysis, while the prognostic impact of MYB family gene expression was evaluated using the Cox proportional hazards model. Additionally, Spearman's correlation analysis was employed to investigate the correlation between MYB family genes and TMB/MSI. The integration of data from various databases demonstrated that all MYB family genes exhibited dysregulated expression in pancreatic cancer. However, only the expression of the MYBL2 gene displayed a notable association with the grade and stage of pancreatic cancer. Furthermore, the MYBL2 gene exhibited significant variations in both univariate and multivariate factor analyses.Subsequent functional analyses revealed a significant correlation between MYBL2 expression in pancreatic cancers and various biological processes, such as DNA replication, tumor proliferation, G2M checkpoint regulation, pyrimidine metabolism, and the P53 pathway. Additionally, a notable positive association was observed between MYBL2 expression and tumor mutational burden (TMB), a predictive indicator for response to PD1 antibody treatment. MYBL2 may be a double marker for independent diagnosis and PD1 antibody response prediction of pancreatic cancer patients.
PubMed: 38947375
DOI: 10.7150/jca.96320 -
Frontiers in Immunology 2024In spite of its high mortality rate and poor prognosis, the pathogenesis of sepsis is still incompletely understood. This study established a cuproptosis-based risk...
Identification and experimental validation of cuproptosis regulatory program in a sepsis immune microenvironment through a combination of single-cell and bulk RNA sequencing.
BACKGROUND
In spite of its high mortality rate and poor prognosis, the pathogenesis of sepsis is still incompletely understood. This study established a cuproptosis-based risk model to diagnose and predict the risk of sepsis. In addition, the cuproptosis-related genes were identified for targeted therapy.
METHODS
Single-cell sequencing analyses were used to characterize the cuproptosis activity score (CuAS) and intercellular communications in sepsis. Differential cuproptosis-related genes (CRGs) were identified in conjunction with single-cell and bulk RNA sequencing. LASSO and Cox regression analyses were employed to develop a risk model. Three external cohorts were conducted to assess the model's accuracy. Differences in immune infiltration, immune cell subtypes, pathway enrichment, and the expression of immunomodulators were further evaluated in distinct groups. Finally, various experiments, such as flow cytometry, Western blot, and ELISA, were used to explore the role of LST1 in sepsis.
RESULTS
ScRNA-seq analysis demonstrated that CuAS was highly enriched in monocytes and was closely related to the poor prognosis of sepsis patients. Patients with higher CuAS exhibited prominent strength and numbers of cell-cell interactions. A total of five CRGs were identified based on the LASSO and Cox regression analyses, and a CRG-based risk model was established. The lower riskScore cohort exhibited enhanced immune cell infiltration, elevated immune scores, and increased expression of immune modulators, indicating the activation of an antibacterial response. Ultimately, experiments demonstrated that LST1, a key gene in the risk model, was enhanced in the macrophage in response to LPS, which was closely related to the decrease of macrophage survival rate, the enhancement of apoptosis and oxidative stress injury, and the imbalance of the M1/M2 phenotype.
CONCLUSIONS
This study constructed a cuproptosis-related risk model to accurately predict the prognosis of sepsis. We further characterized the cuproptosis-related gene LST1 to provide a theoretical framework for sepsis therapy.
Topics: Sepsis; Humans; Single-Cell Analysis; Male; Female; Middle Aged; Prognosis; Sequence Analysis, RNA; Cellular Microenvironment; Aged
PubMed: 38947313
DOI: 10.3389/fimmu.2024.1336839