Clinical Parameters In Patients Research Articles

The Comparison between Spinal Facet Joint Toothed Plate and Traditional Pedicle Screw-rod on Reduction of Thoracolumbar Fracture.

Thoracolumbar fractures are one of the most common fractures in clinical practice. Surgical intervention is recommended to restore spinal alignment or decompress the nerves when there are unstable fractures or neurological injuries. However, after excessive forward thrust force restoration, facet joint dislocation often occurs between the upper vertebra and the fractured vertebra, which usually leads to unsatisfactory reduction outcomes. Herein, we propose a novel spinal facet joint toothed plate to assist in fracture reduction. The purpose of this study is to evaluate the effectiveness of the new spinal facet joint toothed plate in preventing facet joint dislocation, and its advantages compared to traditional pedicle screw-rod decompression. A total of 26 patients in the toothed plate group and 93 patients in the traditional group who experienced thoracolumbar fracture with reduction were retrospectively included. Relevant patients' information and clinical parameters were collected. Furthermore, visual analogue scores (VAS) scores and Oswestry disability index (ODI) scores were also collected. Moreover, imaging parameters were calculated based on radiographs. Correlated data were analyzed by χ2 test and t test. All patients in this study had no postoperative complications. Postoperative VAS scores and ODI scores (p < 0.001) were statistically significant (p < 0.001) in both groups compared with preoperative scores and further decreased (p < 0.001) at final follow-up. In addition, the postoperative vertebral margin ratio (VMR) (p < 0.001) and vertebral angle of the injured vertebrae (p < 0.001) were significantly improved compared with the preoperative period. There were no significant differences in postoperative VAS scores and ODI scores between the two groups. However, toothed plate reduction significantly improved the VMR (p < 0.05) and vertebral angle (p < 0.05) compared with conventional reduction. Ultimately, the total screw accuracy was 98.72% (sum of levels 0 and I), with 100% screw accuracy in the segment related to the tooth plate in the tooth plate group. The dislocation rate was higher in the conventional group (6.45%) than in the new serrated plate repositioning group (0.00%). The facet toothed plate assisted reduction method prevents facet joint dislocation and improves fracture reduction compared to traditional reduction technique, hence it could be considered as a novel surgical strategy for thoracolumbar fracture reduction.

Body composition analysis using dual-energy x-ray absorptiometry in an Egyptian pediatric sickle cell disease cohort.

Growth failure is commonly encountered in sickle cell disease (SCD). Tissue compartment growth and development are subsequently likely to be altered in such patients. We aimed to analyze body composition in an Egyptian pediatric SCD cohort using dual-energy x-ray absorptiometry (DEXA), one of the most comprehensive and noninvasive assessment methods available. Forty children with SCD ≤18years and 40 healthy youngsters age- and gender-matched were enrolled. Patients' demographic, clinical, and laboratory parameters were obtained from their archived files. All patients and controls were subjected to body composition assessment using a MedixDR-Whole Body DEXA System. In SCD patients; weight and height relative to age Z scores were significantly lower (p<.001), total body lean was significantly higher (p=.006), and total body fat percentage was lower, yet the difference was not statistically significant (p=.09). There were no statistically significant variations in bone mineral density or content, basal metabolic rate, subcutaneous adipose tissue, android/gynoid fat ratio, and visceral adipose tissue. There were no significant gender disparities between SCD patients and controls. Faltering growth in children with SCD should be addressed with a multidisciplinary approach including nutritional support, correction of anemia, and proper medical care. Body composition parameters assessed using DEXA were comparable between cases and controls apart from total body lean. Further clinical studies are needed with multicenter cooperation and a larger sample size to assess the usefulness of DEXA as an assessment tool for body composition in children with SCD.

Abstract PO3-19-04: The CROWN STUDY: A multicenter prospective cohort study of cardiovascular outcomes in premenopausal women with hormone receptor positive breast cancer treated with ovarian suppression and an aromatase inhibitor

Abstract Background: Treatment for premenopausal women with high or intermediate risk hormone receptor (HR)+ breast cancer (BC) includes the concurrent use of ovarian function suppression (OFS) and an aromatase inhibitor (AI) to induce near complete estrogen deprivation (NCED). The long-term cardiovascular (CV) sequela for women treated with NCED is unknown. Premature menopause in non-cancer populations is associated with CV disease. The CROWN study (CaRdiac Outcomes With Near complete estrogen deprivation) will use sophisticated imaging assessments of cardiac dysfunction to understand the evolution of CV injury, as well as biomarker and demographic correlates, with the goal of developing tools to assess and mitigate CV risk. Methods: This is a NIH funded prospective cohort study conducted at 3 regional NCI-supported Cancer Centers (Atrium Health Wake Forest Baptist, Virginia Commonwealth and Duke) that will include premenopausal women, age ≤ 55, with Stage I-III BC following completion of planned chemotherapy, surgery and radiation with an ECOG 0-1. HR+ BC patients will receive an AI and OFS. Women with HR- BC are included as comparators. CV imaging and biomarkers will be obtained at baseline, 1 year and 2 years (Table 1). These assessments will include serial cardiac magnetic resonance (CMR) and coronary computed tomography angiography (CCTA) imaging as well as laboratory measurements, including exploratory biomarkers. The primary objective is to determine the 24-month difference in stress myocardial blood flow as measured by adenosine CMR imaging in both groups. We will correlate CMR imaging with CCTA to provide complementary detail of coronary plaque changes. The study will also assess the relevance of pre-existing risk factors on study outcomes, including an emphasis on racial disparities, and dynamic change in modifiable and treatment related risk factors. We plan to enroll 90 women, 67 in the NCED group and 23 in the HR-group, allowing for a 10% drop out rate. There are two primary types of statistical analyses. The first includes testing hypotheses between group (NCED vs HR-) and within group (longitudinal changes within the NCED group). The second analyses, involve developing predictive equations utilizing a stepwise linear regression approach to determine if patient demographics, clinical parameters and serum biomarkers are associated with cardiovascular changes over time. A total of 17 patients are enrolled as of 07/2023. NCT05309655 Study Procedures XX- XX Citation Format: Susan Dent, Emily Douglas, Sarah Hatcher, Katherine Ansley, Carolyn Park, Nathaniel O'Connell, Mary Hackney, Ralph D'Agostino, Rani Bansal, Renee Avecilla, Monica Brown, Kacey Clayton-Stiglbauer, Igor Klem, Jennifer Jordan, Alexandra Thomas. The CROWN STUDY: A multicenter prospective cohort study of cardiovascular outcomes in premenopausal women with hormone receptor positive breast cancer treated with ovarian suppression and an aromatase inhibitor [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-19-04.

Percutaneous Drainage of Pediatric Pulmonary Abscesses: An Effective Therapy

IntroductionPulmonary abscess is a complication of lung infection with localized necrosis and purulent cavity formation. Pulmonary abscesses are typically managed using antibiotic therapy with anatomic surgical resection reserved as a rescue. Percutaneous drainage is considered relatively contraindicated in some centers due to perceived risk of bronchopleural fistula. However, drain placement has been frequently employed at our institution. The purpose of this study was to review and describe our longitudinal experience. MethodsMedical records of children diagnosed with lung abscess and treated with percutaneous drainage from 2005 through 2023 were reviewed. Patient clinical parameters, follow-up imaging, and clinical outcomes were evaluated. ResultsPercutaneous drainage (n=24) or aspiration alone (n=4) under imaging guidance was performed by interventional radiologists for 28 children with lung abscesses. A single catheter (8–12 Fr) was deployed in the pulmonary abscess cavity and remained for a median of 6 days (IQR: 6-8 days). The median hospital stay was 10 days (IQR: 8.8-14.8 days). The technical success rate for percutaneous drainage or aspiration of primary pulmonary abscesses was 100% (26/26). Two children were later diagnosed with secondarily infected congenital pulmonary airway malformations that were both successfully drained and ultimately surgically resected. The abscess cavities resolved in all patients and catheters were removed upon clinical, radiographic, and laboratory improvement. Complications included the presence of two bronchopleural fistula, both of which were treated with immediate pleural drain placement. ConclusionPercutaneous drainage of pulmonary abscesses is an effective therapeutic option in children and can be considered alongside antibiotics as part of the initial treatment for pulmonary abscesses. Bronchopleural fistula can occur, but at a lower frequency than previously reported. Level of EvidenceLevel V

Epidemiological and molecular study of Providencia rettgeri outbreak at a university hospital during the COVID-19 reference center.

In 2014, Brazil detected New Delhi metallo-β-lactamase (NDM)-producing Enterobacterales from a Providencia rettgeri isolate obtained through surveillance swabs in the Southern region. Subsequently, various species have reported several NDM enzymes. However, comprehensive data on the current epidemiology of NDM-producing P. rettgeri in Brazil remains limited. This study, aimed to provide a detailed characterization of the phenotypic, genotypic, and epidemiological profile of clinical isolates of P. rettgeri NDM. From April 2020 to December 2022, 18 carbapenem-resistant P. rettgeri strains, previously identified using Vitek2®, were isolated at the University Hospital of Londrina. Resistance and virulence genes were assessed through genetic analysis using ERIC PCR and NextSeq (Illumina) sequencing. Statistical analysis was conducted using SPSS version 2.0. Genomic analysis confirmed the presence of β-lactamase blaNDM-1 and blaOXA-1. All isolates showed the presence of the NDM encoding gene and genetic similarity above 90% between isolates. Clinical parameters of patients infected with P. rettgeri exhibited significant association with mechanical ventilation, prior use of carbapenems, and polymyxins. We also report a significant association between P. rettgeri infection and death outcome. This study characterizes NDM-1 metallo-β-lactmases isolates, among P. rettgeri isolates from patients at the University Hospital (HU), during the COVID-19 pandemic. The emergence of this novel resistance mechanism among P. rettgeri poses a significant challenge, limiting the therapeutic options for infections in our hospital.

Surgery Advances in Gynecologic Tumors: The Evolution and Outcomes of Robotic Surgery for Gynecologic Cancers in a Tertiary Center

The integration of innovation into routine clinical practice is faced with many challenges. In 2007, we received the mandate to evaluate how the introduction of a robotic program in gynecologic oncology affected patient-centered care by studying its impact on clinical outcomes and hospital resource utilization. Here we summarize the history and experience of developing a robotic surgery program for gynecologic cancers over 16 years. Analysis of the data indicates that robotic surgery improved perioperative patient clinical parameters, decreased blood loss, complications, and hospital stay, maintained the oncologic outcome, and is cost-effective, resulting in it becoming the dominant surgical approach in gynecologic oncology in a tertiary cancer care institution.

Reduced plasma cortistatin is related to clinical parameters in patients with essential hypertension

BackgroundCortistatin (CST), an endogenous bioactive polypeptide, has been acknowledged for its protective effect against several cardiovascular diseases, but its relationship with hypertension remains unclear. Therefore, we aimed to investigate changes in plasma CST in hypertensive patients and further analyze correlations with blood pressure, metabolic parameters and left ventricular structure and function. MethodsIn this hospital-based study, basic information and plasma samples for evaluating clinically relevant indicators such as total cholesterol (TC), triglycerides (TGs), fasting blood glucose (FGB), serum creatinine (Scr) and CST were collected from 81 essential hypertension patients and 75 normotensive subjects. Plasma CST levels were examined by enzyme-linked immunosorbent assay (ELISA). ResultsCompared with normotensive subjects, plasma CST was significantly lower in hypertensive patients. Plasma CST levels in hypertensive patients without blood pressure control was significantly lower than those of hypertensive patients with blood pressure control. Plasma CST levels were significantly negatively correlated with SBP and serum creatinine (Scr) in the overall population. Furthermore, multivariate logistic regression analysis showed that the OR of CST for hypertension was 0.64 using the unadjusted model, and there was still statistical significance using the four-adjusted model. ConclusionsThe circulating concentration of CST was significantly lower in hypertensive patients and was higher after blood pressure control, suggesting that CST may be a new endogenous protective target for hypertension.

Compare deep learning model and conventional logistic regression model for the identification of unstable saccular intracranial aneurysms in computed tomography angiography.

It is crucial to distinguish unstable from stable intracranial aneurysms (IAs) as early as possible to derive optimal clinical decision-making for further treatment or follow-up. The aim of this study was to investigate the value of a deep learning model (DLM) in identifying unstable IAs from computed tomography angiography (CTA) images and to compare its discriminatory ability with that of a conventional logistic regression model (LRM). From August 2011 to May 2021, a total of 1,049 patients with 681 unstable IAs and 556 stable IAs were retrospectively analyzed. IAs were randomly divided into training (64%), internal validation (16%), and test sets (20%). Convolutional neural network (CNN) analysis and conventional logistic regression (LR) were used to predict which IAs were unstable. The area under the curve (AUC), sensitivity, specificity and accuracy were calculated to evaluate the discriminating ability of the models. One hundred and ninety-seven patients with 229 IAs from Banan Hospital were used for external validation sets. The conventional LRM showed 11 unstable risk factors, including clinical and IA characteristics. The LRM had an AUC of 0.963 [95% confidence interval (CI): 0.941-0.986], a sensitivity, specificity and accuracy on the external validation set of 0.922, 0.906, and 0.913, respectively, in predicting unstable IAs. In predicting unstable IAs, the DLM had an AUC of 0.771 (95% CI: 0.582-0.960), a sensitivity, specificity and accuracy on the external validation set of 0.694, 0.929, and 0.782, respectively. The CNN-based DLM applied to CTA images did not outperform the conventional LRM in predicting unstable IAs. The patient clinical and IA morphological parameters remain critical factors for ensuring IA stability. Further studies are needed to enhance the diagnostic accuracy.

Estrogen Receptor 1 Gene Polymorphism and its Association with Idiopathic Short Stature in North Indian Population.

In the hypothalamic-pituitary-gonadotrophin (HPG) axis, estrogen plays a key role in the bone maturation regulation and growth plates closure. This study was designed to explore the link between single nucleotide polymorphisms (SNPs) in estrogen receptor 1 (ESR1) gene with idiopathic short stature (ISS) susceptibility in the North Indian population. Four SNPs of the ESR1 gene (rs543650, rs6557177, rs2234693 and rs9340799) were genotyped by Sanger sequencing in 52 ISS patients and 68 controls. Linkage disequilibrium (LD) and haplotyping were done by SNPstat and SHESISplus softwares. Extent of LD was determined by calculating D' and r2 values in SNPs paired combinations. A significant positive association was found between rs6557177 and rs543650 genotype and ISS susceptibility as compared to controls. The frequencies of the rs6557177 CC genotype (p=0.030; OR=0.13; 95% CI:0.01-1.10) and rs543650 genotype TT (p =0.043; OR=0.29; 95% CI: 0.09-0.92) were observed to be increased in ISS group as compared with the control group. However, no significant correlation was observed between clinical parameters of patients and these SNPs. rs543650 shown strong LD with rs2234693 and rs9340799, similarly rs2234693 and rs9340799. Our study showed that CC genotype at rs6557177 and TT genotype of rs543650 of ESR1 constitutes risk factor for developing ISS in North Indian children. In the future, these findings may lead to a better understanding of the SNPs associated with ISS susceptibility.

A Review on the Evaluation of Serum Adipokine (adiponectin, leptin) Levels in Cardiovascular Disease: A Systemic Review

Background: This review enumerates current knowledge of adipose tissue and reveals processes by which adipocytes affect obesity and cardiovascular illness. Obesity, according to growing evidence, is a crucial factor that influences cardiometabolic phenotypes. However, the pathogenic mechanisms are still unknown. As per recent reports, adipose tissue interacts with a variety of organs, including the lungs, heart, and kidneys, by secreting multiple cytokines known as adipokines. Aim and Objectives: The current study examines the adipokine (adiponectin and leptin) profiles of adipocytes from the adipose tissue and biochemical and clinical parameters in patients with heart disease (CVD). Methods: Relevant articles were retrieved by screening the following databases: Medline (PubMed, Scopus), Web of Science. Keyword searches included ‘adiponectin’, ‘leptin’, AND ‘cardiovascular disease’, from 2013-2023 (May). The retrieved studies were subjected through a screening procedure to identify case-control, cohort and epidemiological studies that contained the required data. Per preferred reporting items for systematic reviews and (PRISMA) guidelines, we conducted the systematic review. Results: A total of 2377 studies were found relevant, out of which only 90 fulfilled the inclusion criteria. From these 90 studies we reviewed 50 articles that are included in the systematic review. Conclusion: The dysfunction of adipose tissue triggered an alteration in the secretory profile of adipokines, which serves as a signal of metabolic disorder. An imbalance in pro- and anti-inflammatory adipokine formation exacerbates cardiometabolic diseases and CVD challenges

Abstract 3826: Predictive and prognostic factors in NUT carcinoma: A systematic review and individual patient data meta-analysis

Abstract Background: NUT carcinoma (NC) is a rare cancer affecting midline structures and involving the lung, bones, and lymph nodes. Data on NC are limited mostly to case reports and case series. Methods: PubMed, Web of Science, and Scopus were systematically searched for original articles describing confirmed NC patients. A quantitative individual patient data meta-analysis (IPD-MA) analyzing overall survival and risk factors for progression was performed for all NC patients with a clear age at diagnosis. Relevant patient characteristics and clinical parameters were compared in a multivariate Cox regression model. Findings: Out of 4,701 studies screened, 175 studies met the inclusion criteria for the systematic review. 117 (66.9%) were case reports. 284 patients were included in the IPD-MA. 139 (48.9%) patients were male, 145 (51.1%) underwent surgery, 156 (54.9%) received radiotherapy, and 173 (60.9%) developed metastasis. The mean age at diagnosis was 35.82±18.33 and the median OS was 9 months. 77 (27.1%) patients received platinum-based agents, 39 (13.7%) received taxanes, and 15 (5.3%) received BET inhibitors as part of their first-line regiment. Age at diagnosis, gender, and the aforementioned drugs did not significantly influence OS. Presence of metastasis was an independent predictor of poor survival, while radiotherapy and surgery were significantly associated with better survival (table 1). Interpretation: NC is associated with poor survival. Surgery and radiotherapy appear to be more effective treatment strategies, while medical modalities may not play a major role in the treatment of NC. Predictors of overall survival in NUT carcinoma patients. Parameter Hazard ratio 95% confidence interval P-value Age at diagnosis 0.99 0.99-1 0.35 BET inhibitors 0.61 0.28-1.15 0.16 Platinum-based agents 0.73 0.47-1.13 0.16 Taxanes 1.29 0.78-2.1 0.31 Surgery 0.41 0.29-0.58 &amp;lt;0.0001 Female gender 1.12 0.83-1.51 0.45 Metastasis 1.76 1.26-2.49 0.0011 Radiotherapy 0.48 0.36-0.67 &amp;lt;0.0001 Citation Format: Sameeha K. Abdulwali, Abduljalil M. El-Sibai, Saad S. Ali, Abdulaziz M. Alaklabi, Hytham M. Abdalla, Ahmad N. Sabbah, Areez Shafqat, Nader A. Fawzy, Belal N. Sabbah, Ahmed Badran, Tarek Z. Arabi. Predictive and prognostic factors in NUT carcinoma: A systematic review and individual patient data meta-analysis [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 3826.

The relationship between kinesiophobia severity and clinical parameters in patients with mechanical low back pain.

Low back pain is an important widespread health problem that can occur at any age, causing serious socioeconomic losses. The objective of this study is to investigate the relationship between kinesiophobia severity and pain severity, depression, and quality of life in patients with mechanical low back pain. The study sample consisted of 155 patients, of whom 72 were female and 83 were male, aged between 18 and 75years with mechanical low back pain. Quality of life was assessed with the 36-Item Short Form Health Survey (SF-36), pain intensity with the Visual Analogue Scale (VAS), kinesiophobia with the Tampa Kinesiophobia Scale (TKS), and depression with the Beck Depression Inventory (BDI). Patients were divided into the low (TKS ⩽ 37) and high kinesiophobia (TKS > 37) groups according to the scores they obtained from TKS. VAS-pain severity and BDI scores were significantly higher in the high kinesiophobia group than in the low kinesiophobia group (p< 0.001). On the other hand, the SF-36 subscale scores were significantly higher in the low kinesiophobia group than in the high kinesiophobia group (p< 0.001). The TKS scores were moderately correlated with VAS-pain severity (r= 0.470; p< 0.001) and BDI scores (r= 0.584; p< 0.001) in the positive direction, and strongly correlated with all sub-parameters of quality of life in the negative direction (p< 0.001). The results indicated that the severity of kinesiophobia in patients with non-inflammatory low back pain is associated with pain severity, depression, and poor quality of life.

Plasmalogens and Octanoylcarnitine Serve as Early Warnings for Central Retinal Artery Occlusion.

Central retinal artery occlusion (CRAO) is a kind of ophthalmic emergency which may cause loss of functional visual acuity. However, the limited treatment options emphasize the significance of early disease prevention. Metabolomics has the potential to be a powerful tool for early identification of individuals at risk of CRAO. The aim of the study was to identify potential biomarkers for CRAO through a comprehensive analysis. We employed metabolomics analysis to compare venous blood samples from CRAO patients with cataract patients for the venous difference, as well as arterial and venous blood from CRAO patients for the arteriovenous difference. The analysis of metabolites showed that PC(P-18:0/22:6(4Z,7Z,10Z,13Z,16Z,19Z)), PC(P-18:0/20:4(5Z,8Z,11Z,14Z)) and octanoylcarnitine were strongly correlated with CRAO. We also used univariate logistic regression, random forest (RF), and support vector machine (SVM) to screen clinical parameters of patients and found that HDL-C and ApoA1 showed significant predictive efficacy in CRAO patients. We compared the predictive performance of the clinical parameter model with combined model. The prediction efficiency of the combined model was significantly better with area under the receiver operating characteristic curve (AUROC) of 0.815. Decision curve analysis (DCA) also exhibited a notably higher net benefit rate. These results underscored the potency of these three substances as robust predictors of CRAO occurrence.

Association Between Leucopenia, Transaminitis, Nonstructural Protein One Antigen (Ns1Ag) Level, and Thrombocytopenia in Adult Dengue Patients in a Tertiary Care Hospital: A Cross-Sectional Study.

The dengue virus is present throughout the tropics. Thrombocytopenia is one of the severe manifestations of the dengue virus. We studied the association of thrombocytopenia with serum transaminase level, leucopenia, and nonstructural protein one antigen (Ns1Ag) level. Data were taken retrospectively from hospital records after obtaining ethical committee approval. In the study, we included 102 patients with acute febrile illness with clinical features suggestive of dengue fever (dengue Ns1Ag positive, dengue IgM positive, or both). We excluded patients with thrombocytopenia due to other causes. Patients' demographic, clinical, and laboratory parameters were collected. We also noted episodes of bleeding or the need for a platelet transfusion. We did a statistical analysis to find out the correlation between age, sex, leucopenia, transaminitis, Ns1Ag level, and thrombocytopenia and its severity. Multiple regression analysis was used to find thrombocytopenia predictors among aspartate transaminase (AST), alanine transaminase (ALT), Ns1Aglevel, and leucopenia. AST and ALT correlated inversely with thrombocytopenia, with p-values of 0.012 and 0.027, respectively. Ns1Ag and leucopenia were not associated with thrombocytopenia, with p-values of 0.802 and 0.532, respectively (p-values significant at 0.01<= p<=0.05). Serum AST and ALT levels correlate with thrombocytopenia in dengue fever.

SERPINE2 promotes liver cancer metastasis by inhibiting c-Cbl-mediated EGFR ubiquitination and degradation.

Liver cancer is a malignancy with high morbidity and mortality rates. Serpin family E member 2 (SERPINE2) has been reported to play a key role in the metastasis of many tumors. In this study, we aimed to investigate the potential mechanism of SERPINE2 in liver cancer metastasis. The Cancer Genome Atlas database (TCGA), including DNA methylation and transcriptome sequencing data, was utilized to identify the crucial oncogene associated with DNA methylation and cancer progression in liver cancer. Data from the TCGA and RNA sequencing for 94 pairs of liver cancer tissues were used to explore the correlation between SERPINE2 expression and clinical parameters of patients. DNA methylation sequencing was used to detect the DNA methylation levels in liver cancer tissues and cells. RNA sequencing, cytokine assays, immunoprecipitation (IP) and mass spectrometry (MS) assays, protein stability assays, and ubiquitination assays were performed to explore the regulatory mechanism of SERPINE2 in liver cancer metastasis. Patient-derived xenografts and tumor organoid models were established to determine the role of SERPINE2 in the treatment of liver cancer using sorafenib. Based on the public database screening, SERPINE2 was identified as a tumor promoter regulated by DNA methylation. SERPINE2 expression was significantly higher in liver cancer tissues and was associated with the dismal prognosis in patients with liver cancer. SERPINE2 promoted liver cancer metastasis by enhancing cell pseudopodia formation, cell adhesion, cancer-associated fibroblast activation, extracellular matrix remodeling, and angiogenesis. IP/MS assays confirmed that SERPINE2 activated epidermal growth factor receptor (EGFR) and its downstream signaling pathways by interacting with EGFR. Mechanistically, SERPINE2 inhibited EGFR ubiquitination and maintained its protein stability by competing with the E3 ubiquitin ligase, c-Cbl. Additionally, EGFR was activated in liver cancer cells after sorafenib treatment, and SERPINE2 knockdown-induced EGFR downregulation significantly enhanced the therapeutic efficacy of sorafenib against liver cancer. Furthermore, we found that SERPINE2 knockdown also had a sensitizing effect on lenvatinib treatment. SERPINE2 promoted liver cancer metastasis by preventing EGFR degradation via c-Cbl-mediated ubiquitination, suggesting that inhibition of the SERPINE2-EGFR axis may be a potential target for liver cancer treatment.

The use of extracorporeal blood purification therapies and sequential extracorporeal support in patients with septic shock (EROICASS): a study protocol for a national, non-interventional, observational multicenter, prospective study

BackgroundSeptic shock, a critical condition characterized by organ failure, presents a substantial mortality risk in intensive care units (ICUs), with the 28-day mortality rate possibly reaching 40%. Conventional management of septic shock typically involves the administration of antibiotics, supportive care for organ dysfunction, and, if necessary, surgical intervention to address the source of infection. In recent decades, extracorporeal blood purification therapies (EBPT) have emerged as potential interventions aimed at modulating the inflammatory response and restoring homeostasis in patients with sepsis. Likewise, sequential extracorporeal therapy in sepsis (SETS) interventions offer comprehensive organ support in the setting of multiple organ dysfunction syndrome (MODS). The EROICASS study will assess and describe the utilization of EBPT in patients with septic shock. Additionally, we will evaluate the potential association between EBPT treatment utilization and 90-day mortality in septic shock cases in Italy.MethodsThe EROICASS study is a national, non-interventional, multicenter observational prospective cohort study. All consecutive patients with septic shock at participating centers will be prospectively enrolled, with data collection extending from intensive care unit (ICU) admission to hospital discharge. Variables including patient demographics, clinical parameters, EBPT/SETS utilization, and outcomes will be recorded using a web-based data capture system. Statistical analyses will encompass descriptive statistics, hypothesis testing, multivariable regression models, and survival analysis to elucidate the associations between EBPT/SETS utilization and patient outcomes.ConclusionsThe EROICASS study provides valuable insights into the utilization and outcomes of EBPT and SETS in septic shock management. Through analysis of usage patterns and clinical data, this study aims to guide treatment decisions and enhance patient care. The implications of these findings may impact clinical guidelines, potentially improving survival rates and patient outcomes in septic shock cases.

Clinical significance of amphiregulin in patients with chronic kidney disease.

Amphiregulin (AREG) is a ligand of epidermal growth factor receptor (EGFR), which plays an important role in injury-induced kidney fibrosis. However, the clinical significance of serum soluble AREG in chronic kidney disease (CKD) is unclear. In this study, we elucidated the clinical significance of serum soluble AREG in CKD by analyzing the association of serum soluble AREG levels with renal function and other clinical parameters in patients with CKD. In total, 418 Japanese patients with CKD were enrolled, and serum samples were collected for the determination of soluble AREG and creatinine (Cr) levels, and other clinical parameters. Additionally, these parameters were evaluated after 2 and 3years. Moreover, immunohistochemical assay was performed ate AREG expression in the kidney tissues of patients with CKD. Soluble AREG levels were positively correlated with serum Cr (p < 0.0001). Notably, initial AREG levels were positively correlated with changes in renal function (ΔCr) after 2 (p < 0.0001) and 3years (P = 0.048). Additionally, soluble AREG levels were significantly higher (p < 0.05) in patients with diabetic nephropathy or primary hypertension. Moreover, AREG was highly expressed in renal tubular cells in patients with advanced CKD, but only weakly expressed in patients with preserved renal function. Serum soluble AREG levels were significantly correlated with renal function, and changes in renal function after 2 and 3years, indicating that serum soluble AREG levels might serve as a biomarker of renal function and renal prognosis in CKD.

Major Adverse Kidney Events in Pediatric Continuous Kidney Replacement Therapy

Continuous kidney replacement therapy (CKRT) is increasingly used in youths with critical illness, but little is known about longer-term outcomes, such as persistent kidney dysfunction, continued need for dialysis, or death. To characterize the incidence and risk factors, including liberation patterns, associated with major adverse kidney events 90 days after CKRT initiation (MAKE-90) in children, adolescents, and young adults. This international, multicenter cohort study was conducted among patients aged 0 to 25 years from The Worldwide Exploration of Renal Replacement Outcomes Collaborative in Kidney Disease (WE-ROCK) registry treated with CKRT for acute kidney injury or fluid overload from 2015 to 2021. Exclusion criteria were dialysis dependence, concurrent extracorporeal membrane oxygenation use, or receipt of CKRT for a different indication. Data were analyzed from May 2 to December 14, 2023. Patient clinical characteristics and CKRT parameters were assessed. CKRT liberation was classified as successful, reinstituted, or not attempted. Successful liberation was defined as the first attempt at CKRT liberation resulting in 72 hours or more without return to dialysis within 28 days of CKRT initiation. MAKE-90, including death or persistent kidney dysfunction (dialysis dependence or ≥25% decline in estimated glomerular filtration rate from baseline), were assessed. Among 969 patients treated with CKRT (529 males [54.6%]; median [IQR] age, 8.8 [1.7-15.0] years), 630 patients (65.0%) developed MAKE-90. On multivariable analysis, cardiac comorbidity (adjusted odds ratio [aOR], 1.60; 95% CI, 1.08-2.37), longer duration of intensive care unit admission before CKRT initiation (aOR for 6 days vs 1 day, 1.07; 95% CI, 1.02-1.13), and liberation pattern were associated with MAKE-90. In this analysis, patients who successfully liberated from CKRT within 28 days had lower odds of MAKE-90 compared with patients in whom liberation was attempted and failed (aOR, 0.32; 95% CI, 0.22-0.48) and patients without a liberation attempt (aOR, 0.02; 95% CI, 0.01-0.04). In this study, MAKE-90 occurred in almost two-thirds of the population and patient-level risk factors associated with MAKE-90 included cardiac comorbidity, time to CKRT initiation, and liberation patterns. These findings highlight the high incidence of adverse outcomes in this population and suggest that future prospective studies are needed to better understand liberation patterns and practices.

LPL rs264, PROCR rs867186 and PDGF rs974819 Gene Polymorphisms in Patients with Unstable Angina.

Coronary artery disease is caused by changes in the coronary arteries due to the atherosclerotic process and thrombotic changes. A very important role in the development of the atherosclerotic process in the coronary vessels is played by the inflammatory process and the immune response. Due to the important role of lipids and the coagulation process in the atherosclerotic process, research has also focused on genes affecting lipid metabolism and the coagulation system. Lipoprotein lipase (LPL) is an enzyme that metabolises lipids, hydrolysing triglycerides to produce free fatty acids and glycerol. Protein C (PC) is an essential component of coagulation and fibrinolysis. It is activated on the endothelial surface by the membrane-bound thrombin-thrombomodulin complex. Platelet-derived growth factor (PDGF) has a number of important functions in processes related to fibroblast and smooth muscle cell function. Due to their influence on lipid metabolism and coagulation processes, LPL, PROCR (endothelial cell protein C receptor) and PDGF may affect the atherosclerotic process and, thus, the risk of coronary heart disease. The aim of the study was to examine the associations between the LPL rs264, PROCR rs867186 and PDGF rs974819 gene polymorphisms and the risk of unstable angina and selected clinical parameters. The study included 232 patients with unstable angina and 144 healthy subjects as the control group. Genotyping was performed using real-time PCR. There were no statistically significant differences in the distribution of the polymorphisms tested between the patients with unstable angina and the control subjects. The results showed associations between the PROCR rs867186 and PDGF rs974819 polymorphisms and some clinical parameters in patients with unstable angina. In patients with the PDGF rs974819 CC genotype, there were increased values for cholesterol and LDL serum levels in comparison with patients with the PDGF rs974819 CT and TT genotypes. In patients with the PROCR rs867186 AA genotype, HDL serum levels were lower than in patients with the GA genotype. The results of our study did not show that the LPL rs264, PROCR rs867186 and PDGF rs974819 gene polymorphisms were significant risk factors for unstable angina in our population. The results of the study suggest that PDGF rs974819 and PROCR rs867186 may be associated with some parameters of lipid metabolism.

Incidence, Severity and Clinical Correlation of Oxaliplatin Induced Neuropathy in Patients with Colorectal Cancer: A Single Institutional Experience

Background: Colorectal cancer is the third most commonly diagnosed cancer worldwide, and its incidence is increasing in developing countries. Chemotherapy plays a significant role in the treatment of locally advanced and metastatic colorectal cancer. Oxaliplatin has remained the backbone of the treatment of colorectal carcinoma. The primary dose-limiting toxicity of oxaliplatin is neuropathy, which can reduce compliance during therapy and impair daily living activities. With limited data regarding the occurrence of oxaliplatin-induced peripheral neuropathy (OIPN) in the Indian population, we aimed to determine the incidence and severity of oxaliplatin-induced neurotoxicity and its clinical correlation with various clinical parameters in patients with colorectal carcinoma in a cancer care centre from North-East India. Material and Methods: A prospective observational analysis was performed on all histologically confirmed cases of colorectal adenocarcinoma who received oxaliplatin-based chemotherapy either in an adjuvant setting or first-line palliative setting at Dr. B. Borooah Cancer Institute between April 2019 to March 2020. Results: Our study evaluated 76 patients with colorectal carcinoma with a mean age of 54.07 ± 10 years. The majority (65.8%) of the patients had adenocarcinoma of the colon, and 34.2% had rectal adenocarcinoma. Twenty-three (30.3%) patients presented with metastatic disease. Oxaliplatin-based chemotherapy regimens were either CAPOX (72.4%) or FOLFOX (27.6%). Acute OIPN was observed in 59 patients (77.6%), and the most common symptom was cold-induced perioral paraesthesia. The most frequent grade for acute OIPN was grade II (30.3%). Chronic OIPN was seen in 47 (61.8%) patients, with the majority developing grade II neuropathy and was manifested mainly after 4th cycle of chemotherapy. The incidence of OIPN was higher in the patients aged ≥60 years, with a cumulative oxaliplatin dose of &gt; 1000 mg/m2 and baseline low serum magnesium or calcium level. Conclusion: Oxaliplatin is one of the essential chemotherapy drugs used in colorectal cancer with significant dose-limiting toxicity of peripheral neuropathy. Well-timed identification of neuropathic symptoms can increase treatment adherence and improve the patient’s quality of life.&#x0D;