Risk Group Of Patients Research Articles

In-depth analysis of lymph node metastasis-related sialylated protein profiling and their clinical and biological significance in colorectal cancer using mass spectrometry and multi-omics technologies

Colorectal cancer (CRC) lymph node metastasis (LNM) is a crucial factor affecting the prognosis and treatment outcomes of CRC patients. It has been confirmed that altered glycosylation is a key event during CRC lymphatic metastases. Sialylation is one of the most significant glycosylation alterations in tumors. However, the predictive role of sialylation and sialylated protein in CRC remains elusive, especially in CRC-LNM. In this study, we explored and identified 1102 sialylated glycoproteins in CRC-LNM using metabolic labeling strategy and proteomics analysis. Combined with comprehensive analysis with bioinformatics and machine learning algorithms, we screened 25 prognostic sialylation-related genes (SRGs) to construct a new molecular phenotype (LRSRGs-Phenotype) and a prognostic SRG signature (LRSRGs-related Gene Signature) in CRC. Then, we further confirmed that patients in different phenotypes had different prognosis, molecular biological characteristics, immune cell infiltration and could be closely linked to three previously reported immune phenotypes: immune-excluded (Phenotype A), immune-desert (Phenotype B), and immune-inflamed (Phenotype C). Besides, we evaluated and validated the LRSRGs-related gene (ACADM, EHD4, FLOT1, GPC1, GSR, LRRC8A, NGFR, SDHB, and SEC61G) signature and found the risk score was an independent risk factor for CRC prognosis. CRC patients in different risk groups had different somatic mutation, tumor microenvironment and immunotherapy response. Finally, we also identified the potential therapeutic agents for CRC patients in different risk groups. In conclusion, we explored the key sialylated glycoproteins, which may play a key role in tumor LNM and clinical outcomes. And constructed the LRSRGs-phenotype and signature with prognostic and therapeutic predictive value in CRC, hoping to provide reliable scientific basis for future treatments in CRC patients.

Abstract 4135746: Assessing Coronary Artery Disease Severity: Leveraging Inflammatory Markers As a Prognostic Indicators

Introduction: Cardiovascular disease continues to be the leading cause of death and a significant cause of morbidity in the United States. In recent years, there has been increased interest in the role of inflammation in predicting and modifying the risk of coronary artery disease. Of the multitude of inflammatory markers studied subsequently, two of the most easily and widely obtained is the neutrophil to lymphocyte ratio (NLR) and the monocyte to lymphocyte ratio (MLR), which can be calculated from a complete blood count with differential. Multiple retrospective studies have demonstrated that the NLR and MLR have been used to diagnose ACS, predict mortality at a year after ACS, and risk stratify patients prior to percutaneous coronary intervention. Research Question: Are the NLR/MLR useful tools in predicting the severity of coronary artery disease (CAD) in patients admitted to a tertiary medical center in Southern Nevada for ACS between 2021 and 2023? Methods: A sample of n=344 patients was used to examine the potential significance of NLR/MLR to diagnose ACS and for predicting CAD severity. Traditional diagnostic test evaluation was used for determining CAD with a ratio of NLR=3.5 + MLR=0.35 (data medians) as the cut-off value. Patient risk group status (1:low risk to 4:high risk) was used as a binary outcome to test NLR/MLR between low and high risk groups using a nonparametric MWW test of medians. Additionally, ROC analysis was used to estimate an optimized cut-off for NLR/MLR as determined by AUC. Results: Results demonstrate for predicting ACS using the median NLR, sensitivity=88.07; specificity=14.88; PPV=52.01; NPV=54.35), LR(+)=1.03 and LR(-)= 0.80, using the median MLR results showed sensitivity=87.28; specificity=14.11; PPV=50.84; NPV=52.17, LR(+)=1.01 and LR(-)= 0.90. Subpopulation analysis demonstrated a statistically significant difference in NLR between “high risk ACS” vs “Low Risk ACS” (p<0.001). Examination of the ROC curve for predicting the high-risk group suggested an optimized cutoff of NLR=3.7; however, AUC was only 0.617, and sensitivity and specificity were not improved compared to using the median NLR. Conclusion: Our findings suggest that an NLR greater than 3.7 may indicate multivessel involvement or proximal/left main disease in CAD patients. However, due to its low specificity and AUC, NLR alone cannot reliably distinguish between single-vessel and multivessel CAD.

Development of a novel disulfidptosis-correlated m6A/m1A/m5C/m7G gene signature to predict prognosis and therapeutic response for lung adenocarcinoma patients by integrated machine-learning

BackgroundLung adenocarcinoma (LUAD) represents a significant global health burden, necessitating advanced prognostic tools for improved patient management. RNA modifications (m6A, m1A, m5C, m7G), and disulfidptosis, a novel cell death mechanism, have emerged as promising biomarkers and therapeutic targets in cancer.MethodsWe systematically compiled disulfidptosis-correlated genes and RNA modification-related genes from existing literature. A novel disulfidptosis-correlated m6A/m1A/m5C/m7G riskscore was computed using integrated machine-learning algorithms. Transcriptomic data from TCGA and GEO databases were downloaded analyzed. Single-cell RNA-sequencing data from the TISCH database was processed using the Seurat package. Genes’ protein–protein interaction network was constructed using the String database. Functional phenotype analysis was performed using GSVA, ClusterProfiler, and IOBR packages. Consensus clustering divided patients into two distinct groups. Drug sensitivity predictions were obtained from the GDSC1 database and predicted using the Oncopredict package.ResultsThe disulfidptosis-correlated m6A/m1A/m5C/m7G risk score effectively stratified LUAD patients into prognostically distinct groups, demonstrating superior predictive accuracy compared to conventional clinical parameters. Patients in different risk groups exhibited significant molecular and clinical differences. Subsequent analyses identified two molecular subtypes associated with RNA modification and disulfidptosis, revealing differences in immune infiltration and prognosis. Functional enrichment analyses highlighted pathways involving RNA modification and disulfidptosis, underscoring their roles in LUAD pathogenesis. Single-cell analysis revealed distinct features between high- and low-risk status cells.ConclusionThis study introduces a novel disulfidptosis-correlated m6A/m1A/m5C/m7G risk score as a robust prognostic tool for LUAD, integrating insights from RNA modifications and cell death mechanisms. The risk score enhances prognostic stratification and identifies potential targets for personalized therapeutic strategies in LUAD. This comprehensive approach emphasizes the critical roles of RNA modifications and disulfidptosis in LUAD biology, paving the way for future research and clinical applications aimed at improving patient outcomes.

Defective biological activities of high-density lipoprotein identify patients at highest risk of recurrent cardiovascular event.

Low cholesterol efflux capacity and elevated levels of Interleukin-1ß (IL-1ß) are both associated with residual cardiovascular risk in patients with acute myocardial infarction (MI) and may be used as new biomarkers to identify patients at higher cardiovascular risk. We evaluated potential synergetic effect of cholesterol efflux capacity and IL-1ß on recurrent major adverse cardiovascular events (MACE) at one-year in 2012 patients with acute ST- segment elevation MI who underwent primary percutaneous coronary intervention. In addition, we evaluated the contribution to residual risk of HDL biological functions from 20 patients of the two extreme subgroups, focusing on cholesterol efflux capacity and anti-inflammatory properties. Patients with MACE during the first year after the MI had significantly lower serum cholesterol efflux capacity as compared to those without recurrent events and higher level of IL-1ß, both associations were confirmed after multivariate analysis. We found an inverse relationship between CEC and circulating levels of the inflammatory markers IL-1ß, defining a very high risk (Low CEC/High IL-1ß) and a low risk (High CEC/Low IL-1ß) group of patients. Patients combining Low CEC/High IL-1ß exhibited the highest risk of recurrent MACE at one year showing an additive prognostic value of these biomarkers, regardless of all the other clinical or biological factors. In this very high-risk subgroup, patients exhibited reduced HDL-efflux capacity and defective ABCA1 and SR-BI with enhanced pro-inflammatory activity as a potential explanation for our clinical findings. Impaired cholesterol efflux capacity and elevated IL-1β synergistically increase the residual cardiovascular risk in MI patients, which could be explained by reduced HDL-efflux capacity and enhanced HDL pro-inflammatory activity.

Prognostic Impact of PTPN11 mutations in Acute Myeloid Leukemia

Background: The classification of acute myeloid leukemia (AML) is being refined as knowledge of associated genetic alterations increases. The role of the protein tyrosine phosphatase non-receptor type 11 (PTPN11) oncogene is well-established in Noonan syndrome and juvenile myelomonocytic leukemia, although less is known about its implications in adult AML. PTPN11 is involved in RAS/MAPK signaling pathway regulation. In this study, we sought to characterize the co-mutational landscape and outcomes of PTPN11 mutations in patients with AML. Methods: We retrospectively analyzed a database of 645 patients aged > 18 years with AML treated at our institution from 2014 to 2024. The PTPN11wild-type cohort was selected to match age, ECOG score, and Charlson Comorbidity Index (CCI) score median and range of the PTPN11mut cohort. Data was collected on molecular and cytogenetic profiles, European Leukemia Net (ELN) risk, response after induction therapy, and survival. Composite complete response (CCR) was defined as complete response, CR with incomplete hematologic recovery, or CR with partial hematologic recovery. Median relapse-free survival (mRFS) and overall survival (mOS) were compared using the Kaplan Meier method. RFS included patients who had primary refractory disease. Categorical variables were compared using Fisher's exact test. Continuous variables were compared using the unpaired t test. Results: PTPN11 mutations were detected in 35 patients with newly diagnosed AML. Those who received intensive induction had a median age of 62 (range, 24-74), median ECOG score of 1 (range, 0-2), and median CCI score of 4 (range, 2-11). The PTPN11mut non-intensive cohort had a median age of 78 (range, 70-85), ECOG of 2 (range, 1-3), and CCI of 7 (range, 5-12). Within a matched cohort of 216 patients with PTPN11wild-type, both the intensive and non-intensive groups had similar characteristics to their PTPN11mut counterpart . Co-occurring mutations in NPM1 were significantly enriched in the PTPN11mut cohort compared to PTPN11wild-type (46% v. 25%, p=0.015). There were no significant differences in cytogenetic profiles. The frequency of patients in each ELN genetic risk category was similar between the two cohorts. The mOS was 11.2 months in the PTPN11mut cohort and 15.3 months in the PTPN11wild-type cohort (HR=1.31, p=0.236). There were no significant survival differences between PTPN11mut and PTPN11wild-type when stratified by induction treatment intensity. The mOS of the PTPN11mut cohort was significantly shorter than that of the PTPN11wild-type favorable risk group (mOS=not reached [NR], HR=2.42, p=0.006) and PTPN11wild-type intermediate risk group (mOS=23.8 months, HR=1.90, p=0.033) but similar to mOS of the PTPN11wild-type adverse risk group (mOS=12.7 months, HR 0.94, p=0.80). Patients with PTPN11mut favorable risk AML had significantly worse mRFS (6.5 v. 22.8 months, HR 2.24, p=0.041) and shorter mOS than those with PTPN11wild-type favorable risk disease (21 months v. NR, HR 2.11, p=0.166), although the latter did not reach significance. Of note, all patients in the PTPN11mut favorable risk group had NPM1 co-mutations. PTPN11mut intermediate risk patients also had shorter mOS than PTPN11wild-type intermediate risk patients (12.3 v. 23.8 months, HR 2.35, p=0.065), trending toward significance. There was no difference in mOS between PTPN11mut adverse risk and PTPN11wild-type adverse risk (9.5 v. 10.5 months, HR 1.17, p=0.594). PTPN11mut with NPM1wild-type (not stratified by ELN risk) had a mOS of 11.1 months, similar to that of PTPN11mut with NPM1mut (12.3 months, HR 0.64, p=0.336). Conclusions: While PTPN11 mutations frequently co-occur with NPM1 mutations, they are also associated with higher risk mutations. PTPN11mut is associated with shorter OS and earlier relapse in ELN favorable risk AML compared to favorable risk with PTPN11wild-type, despite co-occurring NPM1 mutations. These patients should be considered for stem cell transplant in first remission. Co-occurring NPM1mut alone does not improve the OS of PTPN11mut. The OS of PTPN11mut AML more closely resembles that of ELN adverse risk AML. Overall, PTPN11 mutations are associated with poor prognosis. Larger studies are warranted to support the incorporation of PTPN11 into the ELN criteria for higher risk AML.

Myocardial work assessment to improve baseline risk stratification in patients with transthyretin amyloidosis

BackgroundCardiac transthyretin (ATTR) amyloidosis is an often underdiagnosed and potentially fatal disorder associated with poor survival. The National Amyloidosis Centre (NAC) staging system, based on NT-proBNP level and eGFR value, discriminates patients according to survival rates. However, NAC stage II involves a heterogenous group of patients with variable prognosis. This retrospective single-center study was set up to explore the potential role of myocardial work (MW) analysis to enhance risk stratification of ATTR patients prior to therapy. Methods and Results37 patients diagnosed with ATTR between March 2021 and August 2023 were included. Baseline NT-proBNP and eGFR values were collected and LVEF, GLS and MW parameters were obtained from stored echocardiographic images. Patients were categorized per NAC stage (16 NAC I, 13 NAC II and 8 NAC III). Whereas the survival rate in NAC II and NAC III was significantly worse than in NAC I (p = 0.031 and p = 0.045 respectively), no significant difference was found between NAC II and III. In the ROC analysis, GCW proved to be the best survival predictor (AUC: 0.7) with optimal cut-off value 1294 mmHg%. Patients from NAC stage II were re-stratified according to GCW cut-off into HIGH RISK together with patients from NAC III or LOW RISK together with patients from NAC I. Patients in the HIGH RISK group exhibited a significantly worse prognosis with only 40 % survival at 2 years follow-up. ConclusionOur results demonstrate the advantages of incorporating MW analysis, particularly the use of a GCW cut-off, in the baseline risk stratification of ATTR patients.

Mid-regional pro-adrenomedullin is an independent predictor of cardiovascular outcomes in cardiac surgery, a prospective cohort study in 500 patients

Abstract Background MR-proADM (mid-regional pro-adrenomedullin) is a stable pro-peptide of Adrenomedullin, which is expressed in various cell types such as heart, lung, and renal tissue. It is a prognostic parameter for heart failure (HF) and sepsis as well as all-cause and cardiovascular (CV) mortality. Purpose Considering the characteristics of MR-proADM as a reliable biomarker for adverse events, we aimed to investigate the prognostic impact of MR-proADM in patients undergoing elective cardiac surgery. Methods We prospectively enrolled patients undergoing elective cardiac bypass and/or valve surgery at the department of cardiac surgery between May 2013 and August 2018. Blood samples were taken one day prior to surgery. MR-proADM was measured using an automated immunofluorescence assay. Patients were followed prospectively until endpoints were reached. The primary endpoint was the composite of hospitalization for heart failure (HHF) or CV mortality, the secondary endpoint was postoperative atrial fibrillation (POAF). The multivariate regression model was adjusted for age, sex, NT-proBNP, type of surgery, and CRP-level at baseline. Results A total of 500 patients (146 female [29.2%]; median age 69.8 years [IQR 60.6-75.5]) were followed over a median of 4.6 years (IQR 3.0–5.8). Valve surgery was performed in 214 (42.8%) patients, 160 (32%) underwent a bypass operation and 126 (25.2%) a combined valve and bypass surgery. The median MR-proADM value of the entire study population was 0.58 nmol/L (IQR: 0.44-0.79 nmol/L). Patients were stratified in risk categories based on their MR-proADM values (Low Risk ≤0.63nmol/L, Intermediate Risk 0.63-0.83nmol/L, High Risk >0.84nmol/L). Patients in the highest category presented with higher rates of diabetes mellitus (p <0.001), COPD (p <0.001), HF (p=0.009) and either bypass surgery (p=0.039) or the combination of bypass and valve surgery (p=0.008), compared to patients in the lowest tertile. We observed a significant increase in 5-year’s event rates for HHF/ CV Mortality in patients in higher risk groups (Low Risk 8.6% vs High Risk 37.7%, p <0.001, Figure 1). The adjusted Cox regression model found that MR-pro ADM was independently associated with a risk increase for HHF/ CV Mortality (adjusted HR of 4.45, 95% CI 2.55-8.09; p<0.001, Figure 2) comparing the High Risk to the Low Risk Group. A comparable risk increase could be observed in POAF, with an adjusted HR of 2.61 (High Risk Group vs Low Risk Group, 95% CI 1.46-4.67, p<0.001). Conclusion Within the prospective investigation, MR-pro ADM was found to be an independent predictor for HHF and CV mortality in patients undergoing cardiac bypass and/or valve surgery. Furthermore, there was a consistent predictive potential for POAF. In the era of personalized medicine, preoperative MR-pro ADM levels could help to identify patients at risk for serious adverse events, in order to apply intensified secondary prevention and reduce mortality and morbidity.

A study of intracoronary thrombolytic agents in high thrombotic burden lesions during primary PCI

Abstract Objectives High thrombus burden during Primary PCI begets worst possible outcomes, studies on adjunctive intracoronary thrombolytic agents show heterogeneous1,2 results & have limited long term follow-up. Although early studies support mechanical thrombectomy devices, larger randomized trial show that they are not able to reduce the MACE3, 4. There is no randomised clinical data for sustained mechanical thrombectomy devices till now. Purpose of the study The main purpose of this study is to analyse long term outcomes of low bleeding risk group patients undergoing Primary PCI with high thrombus burden, receiving intracoronary thrombolytic agents as an adjunctive therapy. Methods In this prospective observational single centre study, we analysed one year follow-up data of 108 consecutive primary PCI patients with high thrombus burden (G4, G5) and low bleeding risk, who were stratified into two groups basing on whether they receive intracoronary thrombolytic agent as an adjunctive agent before stent implantation. The primary outcome was NACE (Net Adverse Clinical Events, which include MACE, Death, ST/MI, major bleeding events), secondary outcomes include the individual components of the primary outcomes when analysed separately. Results The primary outcome events occurred in 21 patients (26%) in Primary stent group(PS, n=80), whereas it occurred in 2 patients(6%) in primary intra coronary thrombolysis group(PIT, n=28). Log-Rank (Mantel Cox) NACE curves show that PS group has high events when compared to PIT group(26% Vs 7%, p value – 0.042, Hazard ratio - 2.56; 95% CI - 0.76 – 8.57), there is no statistically significant difference in all other key secondary outcome event curves. Conclusion In patients presenting with STEMI, undergoing primary PCI, with high thrombus burden & low bleeding risk group, those receiving intracoronary thrombolytic agent as the adjunctive therapy before stent implantation, are able to reduce the NACE event rates during the one year of follow-up.Fig1:Log Rank (Mantel Cox) NACE curve

Integrated immunogenomic analyses of single-cell and bulk profiling construct a T cell-related signature for predicting prognosis and treatment response in osteosarcoma

PurposesT cells play a crucial role as regulators of anti-tumor activity within the tumor microenvironment (TME) and are closely associated with the progression of osteosarcoma (OS). Nevertheless, the specific role of T cell-related genes (TCRGs) in the pathogenesis of OS remains unclear.MethodsFirst, we processed single-cell RNA sequencing (scRNA-seq) data of OS from the public databases and performed cell annotation. We identified highly variable genes in each cell type using the "FindAllMarkers" function, explored the distribution of different clusters, and investigated inter-cellular communication patterns via the "CellChat" framework. Then, we used multivariate Cox analysis to construct a TCRG and developed a nomogram to predict survival probabilities for OS patients. Finally, we validated the aforementioned results using various cell lines and investigated the immune cell infiltration, expression of immune checkpoints, chemotherapy sensitivity, and the efficacy of targeted therapies across different risk groups.ResultsFrom the scRNA-seq data, we identified 3,000 highly variable genes, presented the top 10 genes, and validated the expression of core genes across different cell lines.Moreover, our analysis delved into interactions between T cells and other cell types. Our analyses constructed a predictive T cell-related signature (TCRS) that incorporated these prognostic TCRGs, showing a clear prognostic separation between the high-risk and low-risk OS patient groups in multiple cohorts. Survival analysis indicated better outcomes for patients classified in the high-risk group. The low-risk group exhibited elevated levels of CD4 memory resting T cells, contrasting with the higher levels of macrophage M0 observed in the high-risk group via the CIBERSORT algorithm. Furthermore, we observed that the low-risk group exhibitedAQ1 significant up-regulation of immune checkpoint genes (ICGs) and lower Tumour Immune Dysfunction and Exclusion (TIDE) scores, suggesting that they may be suitable for immunotherapy. Conversely, the high-risk group appeared more responsive to chemotherapy and targeted therapies, according to our drug sensitivity analysis.ConclusionIn conclusion, our study identified TCRGs, constructed and validated a TCRS for OS, and assessed immune response and drug sensitivity in different risk groups of OS patients. These findings provide novel insights into personalized treatment strategies for OS, potentially guiding more effective therapeutic interventions.

PRODIGY score predicts respiratory depression in the post-anesthesia care unit: A post-hoc analysis.

Surgical patients who experience respiratory depressive episodes (RDEs) during their post-anesthesia care unit (PACU) admission are at a higher risk of developing subsequent respiratory complications in general care wards. A risk assessment tool for PACU RDEs has not been previously assessed. The PRediction of Opioid-induced respiratory Depression In patients monitored by capnoGraphY (PRODIGY) score is an assessment tool that uses baseline patient variables to categorize patients into low, intermediate, or high risk groups for RDEs in general care wards. This study assessed whether PRODIGY groups are associated with PACU RDEs. This analysis utilized data from a previous observational trial of PACU RDEs detected by capnography. PRODIGY scores were retrospectively calculated, and the number and duration of respiratory alerts were compared among PRODIGY groups. Twenty-six (29.9%) patients were classified as low risk, 29 (33.3%) as intermediate risk, and 32 (36.8%) as high risk. A total of 3,580 alerts were recorded in the PACU, 47% of which were apnea episodes lasting ≥ 10 seconds. The total number and duration of alerts were highest in high risk group patients (median 56 [IQR 12 - 87] alerts per patient vs 22 [9 - 37] in low risk and 26 [13 - 42] in intermediate risk patients, P = 0.035; 303 [123 - 885] seconds vs 177 [30 - 779] in low risk and 301 [168 - 703] in intermediate risk patients, P = 0.042). Poisson regression analysis indicated that the rate of RDEs in the high PRODIGY risk group was higher than in the intermediate (rate ratio estimate = 2.01 [95% CI 1.86 - 2.18], P < 0.001) and low (rate ratio estimate = 2.25 [95% confidence interval 2.07 - 2.45], P < 0.001) risk groups. This analysis suggests that the PRODIGY score may be useful in assessing the risk of PACU RDEs. Trial Registration: https://www.clinicaltrials.gov/ct2/show/NCT02707003.

Identification and experimental validation of a sialylation–related long noncoding RNA signature for prognosis of bladder cancer

BackgroundThe dysregulation of sialylation plays a pivotal role in cancer progression and metastasis, impacting various aspects of tumor behavior. This study aimed to investigate the prognostic significance of long non-coding RNAs (lncRNAs) in relation to sialylation. Additionally, we aimed to develop a signature of sialylation-related lncRNAs in the context of bladder cancer.MethodsThis study used transcriptomic data and clinical information from the TCGA (the Cancer Genome Atlas) database to screen for sialylation-related lncRNAs and constructed a prognostic model. The relationships between these lncRNAs and biological pathways, immune cell infiltration, drug sensitivity, etc., were analyzed, and the expression of some lncRNAs was validated at the cellular level.ResultsThis study identified 6 prognostic lncRNAs related to sialylation and constructed a risk score model with high predictive accuracy and reliability. The survival period of patients in the high-risk group was significantly lower than that of the low-risk group, and it was related to various biological pathways and immune functions. In addition, this study found differences in the sensitivity of patients in different risk groups to chemotherapy drugs, providing a reference for personalized treatment.ConclusionIn this study, we examined the relationship between sialylation-related lncRNA and the prognosis of bladder cancer, providing new molecular markers and potential targets for diagnosis and treatment. Our research revealed correlations between sialylation-related lncRNA characteristics and clinicopathological features, potential mechanisms, somatic mutations, immune microenvironment, chemotherapy response, and predicted drug sensitivity in bladder cancer. Additionally, in vitro cellular studies were conducted to validate these findings and lay the groundwork for future clinical applications.

Risk factors for multidrug-resistant bacteria in critically ill children and MDR score development.

Antimicrobial resistance and healthcare-associated infections (HAIs) are major health concerns in the pediatric intensive care unit (PICU). Device-associated HAIs (DA-HAIs) produced by multidrug-resistant (MDR) bacteria are especially worrying, as they can lead to an inappropriate empirical antibiotic therapy, worsened outcomes and increased mortality. The MDR score was designed to enable the prompt identification of patients at high risk of developing an MDR infection. This was a single-center, prospective, observational study, conducted between January 2015 and December 2022, including PICU patients with a microbiologically confirmed DA-HAI. Demographic, clinical characteristics and outcomes were compared between patients with a DA-HAI caused by MDR and non-MDR-associated DA-HAI, and a risk score for multi-resistance was designed. In total, 257 DA-HAI cases were included, 86 (33.46%) caused by an MDR microbe. In the univariate analysis, comorbidity (p = 0.002), previous MDR colonization (p < 0.001), previous surgery (p = 0.018), and previous antibiotic therapy (p = 0.009) were more frequent among MDR-associated DA-HAI (MDR DA-HAI). In addition, days from device insertion to infection and from PICU admission (p < 0.005) to infection were longer in patients with MDR. In the multivariate analysis, previous comorbidity (OR 2.201), previous MDR colonization (OR 5.149), and PICU length of stay longer than 9days (OR 1.782) were independently associated with MDR-DA-HAI. Using these three independent risk factors for MDR, a risk score was created: the MDR score. Three risk groups were obtained: low risk (0-2 points), intermediate risk (3-7 points), and high risk (8-12 points). Seventy-one patients with MDR-DA-HAI (82.6%) were classified in the intermediate or high-risk group, with a global sensitivity of 82.6%. The specificity in the high-risk group was 91.8%, and 81.0% of patients who were stratified into the low-risk group had non-MDR-associated infections, so they were correctly classified. Conclusions: The MDR score can be a useful tool to stratify patients in risk groups for MDR-DA-HAI. It may help to guide the choice of empirical therapy, leading to early optimization and avoiding delays in establishing appropriate treatment. This study reinforces the importance of stratifying patients based on their individual risk profile for MDR infection.

Predicting Survival Among Colorectal Cancer Patients: Development and Validation of Polygenic Survival Score.

Colorectal cancer is the second leading cause of cancer-related death in the United States. A multi-omics approach has contributed in identifying various cancer-specific mutations, epigenetic alterations, and cells response to chemotherapy. This study aimed to determine the factors associated with colorectal cancer survival and develop and validate a polygenic survival scoring system (PSS) using a multi-omics approach. Data were obtained from the Cancer Genome Atlas (TCGA). Colon Adenocarcinoma (TCGA-COAD) data were used to develop a survival prediction model and PSS, whereas rectal adenocarcinoma (TCGA-READ) data were used to validate the PSS. Cox proportional hazards regression analysis was conducted to examine the association between the demographic characteristics, clinical variables, and mRNA gene expression. Overall accuracy of PSS was also evaluated. The median overall survival for TCGA-COAD patients was 7 years and for TCGA-READ patients was 5 years. The multivariate Cox proportional hazards model identified age, cancer stage, and expression of nine genes as predictors of colon cancer survival. Based on the median PSS of 0.38, 48% of TCGA-COAD patients had high mortality risk. Patients in the low risk group had significantly higher 5-year survival rates than those in the high group (p <0.0001). The PSS demonstrated a high overall accuracy in predicting colorectal cancer survival. This study integrated clinical and transcriptome data to identify survival predictors in patients with colorectal cancer. PSS is an accurate and valid measure for estimating colorectal cancer survival. Thus, it can serve as an important tool for future colorectal cancer research.

Transurethral Diode Laser Ablation of Prostate Vs Bipolar Transurethral Vaporization of Prostate, A Prospective Randomized Controlled Study

Abstract Background Vaporization/Ablation of prostate is becoming one of the standard modalities for treating of symptomatic cases of lower urinary tract symptoms (LUTS) due to benign prostatic hyperplasia (BPH) especially in men with bleeding tendency. Objective to compare the short term safety and efficacy of bipolar plasma versus laser ablation of prostate and follow up over 6 months post operative. Patients and Methods This prospective randomized control study (double armed) included 60 patients with prostates less than 80 gm operated upon and followed up in the Urology Department of Ain Shams University hospitals. The patients were divided into 2 groups: Group A 30 Patients underwent Transurethral Diode Laser Ablation, Group B 30 Patients underwent Bipolar Transurethral Vaporization as the control group. Results When we compared both groups of patients there was no great difference and both techniques proved great efficiency and safety on patients especially in high risk group of patients, and both of them resulted in improvement in all parameters of LUTS secondary to BPH (decrease of IPSS, increase of Q max, decrease of residual urine and PSA). There was no risk or major complication encountered in the study e.g. no significant bleeding and no risk of TUR syndrome. However operation time was shorter in laser group 22 (mean) min compared to 49 min in bipolar group. Also the mean cost of laser group was about 30000 EGP and the mean cost of bipolar group was 20000 EGP in Ain Shams University hospital. Also catheter time was shorter in laser prostatectomy 24 hours versus 48 hours in bipolar, this is done in trial to lessen the irritative effect of vaporization on the nerve ending, and avoid the expected dysuria. Conclusion Both techniques are considered safe and effective, similar in the outcome and both techniques has excellent hemostatic profile with no serious complications occurred in both groups. Laser is a faster technique than bipolar however it's more expensive.

New histological risk grading system for prediction of lymph node metastasis in patients with penile cancer

AbstractInguinal lymph node surgery is a standard treatment for penile cancer patients with intermediate or high risk for lymph node metastasis (LNM) according to European Association of Urology (EAU) risk grading. We are proposing a more objective histological prognostic grading system for inguinal LNM in these patients. We assessed worst pattern of invasion, lymphocytic host response, lymphovascular invasion, and perineural invasion in a population-based cohort of 306 penile cancer patients. Patients were classified into low, intermediate, and high risk for inguinal LNM. There was a significant association both between risk groups and pT stage (p &lt; 0.001) and between risk groups and LNM. Univariate logistic regression showed 25.43 times higher odds of LNM for patients in the intermediate risk group compared with the low risk group (odds ratio (OR) 25.43; 95% confidence interval (CI): 5.94–108.97) and a 177.13 times higher odds in the high risk group compared to the low risk group (OR 177.13; 95% CI: 40.09–782.51). When comparing our histological risk grading with the EAU grading, we found a higher sensitivity, of 51.28% (95% CI: 45.68–56.88) versus 37.09% (95% CI: 31.68–42.50), as well as a higher area under the curve (0.86; 95% CI: 0.81–0.89; versus 0.65; 95% CI: 0.58–0.71) with our grading system. While our grading classified 111 patients as low risk, only 31 were considered low risk for LNM according to the EAU risk classification. The new histological risk grading system shows a higher sensitivity and includes a higher number of patients in the low risk group in whom lymph node surgery could be avoided, reducing morbidity and costs.

Impact of spliceosome mutation on outcomes of myelodysplastic syndrome and chronic myelomonocytic leukemia patients undergoing allogeneic hematopoietic cell transplantation

IntroductionAllogeneic Hematopoietic cell transplantation (allo-HCT) remains the only curative therapy for myelodysplastic syndrome (MDS) and chronic myelomonocytic leukemia (CMML). The impact of spliceosome mutations on allo-HCT outcome is unclear and further understanding is needed to assess the implications of this class of mutations on risk of relapse, overall survival (OS) and non-relapse mortality (NRM) in order to make decision regarding timing of allo-HCT. We examined the allo-HCT outcomes of MDS/CMML patients based on their spliceosome mutation profile to understand the impact of these mutations on transplant outcomes. ObjectiveTo compare outcomes of MDS/CMML patients with and without spliceosome mutations undergoing allo-HCT. MethodsThis is a single institution, retrospective study of MDS/CMML patients who underwent allo-HCT with myeloablative or reduced intensity conditioning (RIC) regimen at City of Hope from January 2016 to December 2021. Among them, patients who underwent molecular mutation profiling by NGS (Next Generation Sequencing) for a set of genes known to be mutated in myeloid neoplasms are included in this analysis. We compared OS, relapse free survival, NRM and acute/chronic graft versus host disease (GVHD) incidence between the spliceosome-mutated and unmutated groups. ResultsWe identified 258 consecutive MDS/CMML patients who underwent allo-HCT. Of these, 126 (48.8 %) patients had molecular profiling done among whom 57 (45.2 %) patients carried a spliceosome mutation. 84.9 % of patients had MDS and 55.6 % underwent a matched unrelated donor transplant. The median age for the whole cohort was 66 years (range 12–77).78.6 % and 73.7 % received RIC in the spliceosome and non-spliceosome groups, respectively. The 2-year OS for the whole cohort was 66.5 % (95 %CI 0.55–0.75) with a day 100 NRM of 7.1 % and 2-year cumulative incidence of relapse of 20 %. Grade II-IV acute GVHD at day 100 was 36.3 % (95 % CI 0.27–0.44) and any chronic GVHD at 2-years was 48.4 % (95 % CI 0.37–0.58). Patients who carried a spliceosome mutation had a significantly better 2-year survival of 83.8 % vs 55.9 % in the non-spliceosome group (P=0.002) and a better PFS of 73.7 % vs 50.0 % (P=0.007). There was no difference in the cumulative incidence of relapse at 2-years 15.9 % vs 18.5 % (P=0.59) between two groups but the spliceosome group had a significantly lower NRM at 2-years 10.4 % vs 31.5 % (P=0.009). There was no difference in incidence of acute or chronic GVHD between the two groups. ConclusionsAmong patients with MDS or CMML who underwent allo-HCT, our study shows better OS for patients who have spliceosome mutations due to lower NRM compared to those carrying non- spliceosome mutations. This favorable outcome of the spliceosome-mutated patients could have implications for timing of allo-HCT, particularly for patients in the intermediate MDS prognostic risk groups.

Effect of Preoperative Lipidemic Control on Retear Rates After Rotator Cuff Repair in Patients With Hyperlipidemia

Background: In patients with hyperlipidemia, the risk of retear increases after rotator cuff repair (RCR). In particular, it has been reported that preoperative low-density lipoprotein cholesterol (LDL-C) level affects cuff integrity. However, there are no studies assessing whether lipidemic control affects cuff healing. Purpose: To evaluate the effect of preoperative lipidemic control on cuff integrity after arthroscopic RCR across cardiovascular disease risk groups in patients with hyperlipidemia. Study Design: Case-control study; Level of evidence, 3. Methods: The authors retrospectively reviewed the charts of patients with hyperlipidemia who underwent arthroscopic double-row suture bridge RCR between 2014 and 2019. The included patients had LDL-C tested within 1 month before surgery. Magnetic resonance imaging was conducted 6 months after surgery to evaluate the integrity of the repaired cuff tendon. Patients were divided into groups of low, moderate, high, and very high risk according to the 4th Korean Dyslipidemia Guidelines. On the basis of the target LDL-C set in each risk group, patients were categorized into 2 groups: group C (controlled hyperlipidemia, less than target LDL-C) and group U (uncontrolled hyperlipidemia, target LDL-C or greater). The correlation between serum lipid profile, lipidemic control, and post-RCR integrity was evaluated. Results: A total of 148 patients were analyzed, 51 in group U and 97 in group C. The retear rate was significantly higher in group U than in group C (23/51 [45.1%] vs 18/97 [18.6%], respectively; P = .001). The proportion of group U was significantly higher in the retear group than in the healing group (56.1% vs 26.2%; P = .001). In addition, the proportions of patients with uncontrolled diabetes mellitus (DM) (19.5% vs 3.7%; P = .002) and mediolateral (2.6 ± 1.2 cm vs 1.7 ± 1.1 cm; P < .001) and anteroposterior (2.2 ± 1.1 cm vs 1.6 ± 0.8 cm; P = .003) tear sizes were significantly different between the retear and healing groups, respectively. No significant difference in serum lipid profile, including LDL-C level (119.6 ± 31.3 vs 116.7 ± 37.2; P = .650), was observed between the retear and healing groups. Multivariate regression analysis identified uncontrolled hyperlipidemia (OR, 4.005; P = .001), uncontrolled DM (OR, 5.096; P = .022), and mediolateral tear size (OR, 1.764; P = .002) as independent risk factors for retear. The 2.0-cm mediolateral size cutoff and the 3 independent risk factors had significant associations with retear. Conclusion: Poor preoperative lipidemic control was significantly associated with poor healing after RCR. In addition to large mediolateral tear size, uncontrolled hyperlipidemia and DM were significant risk factors for retear. Moreover, poor lipidemic control compared with the recommended target level before surgery was more correlated with an increased retear rate than a preoperative LDL-C level.

Treatment results of lymphoblastic lymphomas from progenitor cells according to ALL IC-BFM 2002/2009 protocols: monocenter clinical trial

Introduction. The acute lymphoblastic leukemia (ALL) therapy programs developed by the BFM group (Berlin-Frankfurt-Munster) are used to treat lymphoblastic lymphomas from precursor cells (LBL) and are the most effective treatment methods in the world.Aim. To assess the treatment results of LBL in children according to the ALL IC-BFM 2002/2009 protocols in a clinical trial of a single center.Materials and methods. From 2002 to 2022 a retrospective and prospective study included 70 patients aged 2 to 17 years with newly diagnosed LBL, with a median age of 9.4 years. There were 1.5 times more male patients than female (43:27). LBL from T-cells progenitor (T-LBL) was diagnosed in 61 patients (87 %), and LBL from B-cells progenitor (B-LBL) — in 9 (13 %). 59 (84.3 %) patients were included in the intermediate risk (IR) group and 11 (15.7 %) patients — in high-risk (HR) group. There were no patients in the study cohort who met the criteria of the standard risk group (SR).Results. The 10-year OS in the group of patients treated according to the ALL IC-BFM 2002/2009 protocols was 95.4 ± 2.6 %; the 10-year RFS — 91.9 ± 4.9 %; the 10-year EFS — 86.7 ± 5.6 %. When analyzing survival rates depending on the prognostic risk group, the 10-year OS for patients of the intermediate risk group was 96.6 ± 2.6 %, and for patients of the high-risk group — 90.9 ± 8.7 %.Conclusions. The obtained results confirm the high effectiveness of the ALL IC-BFM 2002/2009 protocols in the treatment of LBL.

Impact of the American Society of Anesthesiologists (ASA) classification on hip fracture surgery outcomes: insights from a retrospective analysis

BackgroundThe American Society of Anesthesiologists (ASA) classification is the most used system to assess patient health status before surgery, ranging from I to V levels. This study aims to explore the impact of different ASA risk classes (ASA II [mild risk] and ASA III [severe risk]) on clinical outcomes following hip fracture surgery, including all-cause mortality and postoperative complications.MethodsA retrospective analysis from 2019 to 2021 across three Jordanian centers was conducted. The study included patients aged 65 and above who underwent hip fracture repair surgeries. Preoperative measures, intraoperative management protocols, and postoperative care were collected. Clinical data were extracted from electronic medical records, including demographics, fracture type, intraoperative data, and postoperative outcomes.ResultsThe analysis included 1033 patients, with 501 (48.5%) in the mild anesthetic risk group (ASA I-II) and 532 (51.5%) in the severe anesthetic risk group (ASA III-V). The mean age was 73 years, with a higher prevalence of males in the severe risk group. Patients in the severe risk group had more comorbidities, higher ICU admissions (15.23% vs. 6.18%), longer hospital stays (median 7 vs. 6 days), and higher rates of postoperative thromboembolic complications (3.39% vs. 1.39%) compared to the mild risk group. Additionally, the severe risk group showed higher mortality rates both in-hospital mortality (3.38% vs. 1.39%) and all-cause mortality (16.92% vs. 10.36%). Multivariate analysis identified higher ASA score as independent risk factors for increased all-cause mortality (HR = 1.64 95%CI 1.51–2.34) and thromboembolic complications (OR = 2.85 95%CI 1.16-7). Length of hospital stay was significantly associated with higher ASA score (OR = 1.04 95%CI 0.96–1.11).ConclusionThe study underscores the significant impact of anesthetic risk on the outcomes of hip fracture surgeries. Patients with higher ASA scores associated with severe systemic diseases may have at increased risk of adverse outcomes.

Extrahepatic Portal Venous Gas Is the Strongest Predictor of Mortality in Patients with Portal Venous Gas and Pneumatosis Intestinalis.

Very few studies have examined the association between contrast-enhanced computed tomography (CT) findings observed in portal venous gas (PVG) and pneumatosis intestinalis (PI) and the underlying diseases in these conditions. In this study, we analyzed this association and report the findings for predicting mortality. Overall, 50 patients diagnosed with PVG or PI, observed on contrast-enhanced CT, underwent treatment at our hospital. Based on the underlying disease, we divided the patients into three groups, those with ischemic disease, infectious disease, or gastrointestinal dilatation. Furthermore, cases that underwent surgical treatment or needed surgery but were inoperable were assigned to the high risk group (n=16) and patients who received conservative treatment were assigned to the low risk group (n=34). We reviewed the patients' medical charts, laboratory data, and CT images retrospectively, and analyzed the relationship between CT findings, underlying disease, and association with the high risk or low risk group in each case. Poor enhancement of the intestinal wall, mesenteric fat stranding, extrahepatic PVG, advanced age, and renal disease were significantly associated with ischemic disease (p=0.02, p=0.02, p=0.005, p=0.008 and p=0.049, respectively). PI alone was strongly associated with gastrointestinal dilatation (p=0.009). Patients in the low risk group had more favorable outcomes with conservative treatment. In multivariate analysis, extrahepatic PVG was the only factor associated with the high risk group (p=0.002). Extrahepatic PVG associated with ischemic disease was the strongest predictive factor of mortality. Other CT findings, though useful in diagnosing the underlying disease, were not significant predictive factors.