High-risk Patients Research Articles

Impact of COVID-19 in the incidence of venous thromboembolism (VTE) and clinical outcomes in cancer patients: a cohort study.

To determine the incidence of VTE and clinical outcomes in a cohort of cancer patients and COVID-19 infection, and to establish possible predictive factors of VTE. A single-center retrospective cohort study was performed to determine the incidence of VTE and mortality in 118 cancer patients with SARS-CoV-2 infection from March to August 2020. We calculated individual Khorana Risk and CATS-MICA scores in order to evaluate their utility to identify risk of VTE or death. Continuous variables were compared using Wilcoxon or Student's T test, and categorical variables were compared using the Chi-Square or Fisher's exact text among patients with and without VTE. A Log-Rank test was performed to detect mortality differences between the groups. A total of 118 patients were included. VTE global incidence was 4.2% (n = 5), and mortality 25.4% (n = 30). Obesity (p = 0.05), recent chemotherapy (p = 0.049) and use of steroids (p = 0.006) were related to higher risk of VTE in the univariate analysis, although they were not confirmed in the multivariate analysis as independent risk factors. Statistically significant differences in all-cause, COVID-19-related and cancer-related mortality according to the Khorana risk score (KRS) were observed. CATS-MICA score (CMS) also showed statistically significant differences in mortality between low- and high-risk patients. Prediction of risk of VTE development with these scores showed a tendency towards significance. In this cohort, VTE incidence was similar to previously reported in the general population with SARS-CoV-2 infection. KRS was associated with overall and specific-cause mortality, and might be a useful prognostic tool in this setting.

Prehospital point-of-care medication burden as a predictor of poor related outcomes in unselected acute diseases.

How prehospital medication predicts patient outcomes is unclear. The aim of this work was to unveil the association between medication burden administration in prehospital care and short, mid, and long-term mortality (2, 30, and 365day) in unselected acute diseases and to assess the potential of the number of medications administered for short, mid, and long-term mortality prediction. A prospective, multicenter, ambulance-based, cohort study was carried out in adults with unselected acute diseases managed by emergency medical services (EMS). The study was carried out in Spain with 44 ambulances and four hospitals. The principal outcome was cumulative mortality at 2, 30, and 365days. Epidemiological variables, vital signs, and prehospital medications were collected. Patients were classified into four categories: no medication dispensed in prehospital care, one to two medications, three to four medications, and five or more medications. A total of 6401 patients were selected. The 2-day mortality associated with each group was 0.5%, 1.8%, 6.5%, and 18.8%. The 30-day mortality associated with each group was 3.8%, 6.2%, 13.5%, and 31.9%. The 365-day mortality associated with each group was 11%, 15.3%, 25.2%, and 45.7%. The predictive validity of the number of drugs administered, measured by the area under the curve, was 0.808, 0.720, and 0.660 for 2-, 30-, and 365-day mortality, respectively. Our results showed that prehospital drugs could provide relevant information regarding the mortality prediction of patients. The incorporation of this score could improve the management of high-risk patients by the EMS.

A workplace violence prevention program targeting high-risk patients in emergency departments.

Patient violence in emergency departments (EDs) may be prevented with proactive mitigation measures targeting potentially violent patients. We aimed to evaluate the effects of two interventions guided by a validated risk-assessment tool. A prospective interventional study was conducted among patients ≥10 years who visited two EDs in Michigan, USA, from October 2022 to August 2023. During triage, the ED nurses completed the Aggressive Behavior Risk Assessment Tool for EDs (ABRAT-ED) to identify high-risk patients. Following the baseline observational period, interventions were implemented stepwise for the high-risk patients: phase 1 period with signage posting and phase 2 period with a proactive Behavioral Emergency Response Team (BERT) huddle added to the signage posting. Before ED disposition, any violent events and their severities were documented. The data were retrieved retrospectively after the study was completed. Of 77,424 evaluable patients, 546 had ≥1 violent event. The violent event rates were 0.93%, 0.68%, and 0.62% for baseline, phase 1, and phase 2, respectively. The relative risk of violent events for phase 1 compared to the baseline was 0.73 (95% confidence interval [CI]: 0.59‒0.90; p=0.003). The relative risk for phase 2 compared to phase 1 was 0.92 (95% CI: 0.76‒1.12; p=0.418). The use of signage posting as a persistent visual cue for high-risk patients identified by ABRAT-ED appears to be effective in reducing the overall violent event rates. However, adding proactive BERT huddle to signage posting showed no significant reduction in the violent event rates compared to signage posting alone.

Apalutamide for High-Risk Localized Prostate Cancer Following Radical Prostatectomy (Apa-RP).

Approximately 25 to 50% of patients with high-risk localized prostate cancer experience biochemical recurrence within 2 years of radical prostatectomy. The Apa-RP study (NCT04523207) investigated whether adjuvant apalutamide plus androgen deprivation therapy in high-risk patients who have undergone radical prostatectomy improved biochemical recurrence-free survival. Apa-RP was a multicenter, open-label, single-arm, phase 2 study conducted in community urology practices in the United States. High-risk patients who had radical prostatectomy received 12 cycles of apalutamide (240 mg daily; 28-day cycles) plus androgen deprivation therapy. The primary endpoint was biochemical recurrence-free survival. Secondary endpoints included testosterone recovery (≥150 ng/dL) and safety. One hundred eight patients were enrolled; median age was 66.0 years (range 46.0-77.0). Median pre-operative prostate specific antigen and baseline testosterone were 7.6 ng/mL (range 2.2-62.7) and 340.0 ng/dL (range 43.0-939.0), respectively. The biochemical recurrence-free rate at 24 months (12 months after completion of planned therapy) was 100% (90% CI 93-100). Serum testosterone recovery rate (≥50 and ≥150 ng/dL) 12 months after treatment completion was 96% (95% CI 88-98) and 77% (95% CI 66-85), respectively. Overall, 107 (99%) patients experienced treatment-emergent adverse events, with 24 (22%) experiencing grade 3 to 4 events. In Apa-RP, BCR-free survival was 100% with 77% of patients having testosterone recovery (≥150 ng/dL) within 12 months of actual treatment completion and a manageable safety profile. These results provide proof of concept that treatment intensification with 12 cycles of apalutamide plus ADT could become an option for patients with high-risk localized prostate cancer who have undergone radical prostatectomy.

Leadless Pacemakers: A Retrospective Analysis of Efficacy, Safety, and Applicability in High-Risk Patients at a Single Centre in North Queensland

Leadless Pacemakers: A Retrospective Analysis of Efficacy, Safety, and Applicability in High-Risk Patients at a Single Centre in North Queensland

Wearable defibrillator to improve accuracy in selecting candidates to implantable defibrillator: A real-world experience.

The indication for implantable cardioverter defibrillator (ICD) for sudden cardiac death (SCD) prevention relies mostly on left ventricular ejection fraction (LVEF)≤35%. The use of a wearable cardioverter defibrillator (WCD) in the case of dynamic alterations of LVEF may help avoid an improper early ICD implant when a favourable evolution in the post-acute phase is observed and may help reduce costs. This parallel cohort retrospective study included patients with heart failure with reduced ejection fraction (HFrEF) at high risk of arrhythmias recruited in the acute phase and divided into an early ICD cohort and a WCD cohort for primary prevention during the waiting period established by European Society of Cardiology guidelines. A total of 41 consecutive patients were enrolled: 26 in the WCD group and 15 in the early ICD group. Age, LVEF at baseline, causes of HFrEF and drug therapy in the two cohorts were similar. During the waiting period after the inclusion, three patients (11.5%) in the WCD cohort and four (26.7%) in the early ICD cohort developed relevant ventricular arrhythmias (P=0.22); none of them had subsequent LVEF recovery. At the end of the waiting period, 13 patients (50%) in the WCD group and 7 (46.7%) in the early ICD group experienced LVEF recovery (P=0.84). The average cost per patient at the end of the waiting period was €23934 in the early ICD cohort versus €19167 in the WCD cohort (-19.9%). This cost savings from WCD use appears even higher when projected over a 10year period (-41.2%). WCD may represent a cost-effective strategy to more accurately select candidates for the primary prevention ICD implant among high-risk patients with HFrEF. ICD use provides effective protection from SCD and reduces costs compared with an extensive early ICD implant.

Characteristics and outcomes of patients treated with sotrovimab to prevent progression to severe COVID-19 in Belgium

ABSTRACT Objective Sotrovimab, a dual-action, engineered human monoclonal antibody, has been demonstrated to significantly reduce the risk of hospitalisation and death in high-risk patients with COVID-19. Here, we describe the real-world use of, and outcomes from, sotrovimab treatment in Belgium during the Delta and Omicron waves among patients with COVID-19 at high risk of developing severe disease. Methods This was a multicentric, single-arm observational cohort study of non-hospitalised patients receiving outpatient sotrovimab treatment between 1 November 2021 and 2 August 2022 at nine hospitals in Belgium. The primary outcomes were all-cause and COVID-19-related hospitalisations and all-cause deaths during the 29-day acute follow-up period from first administration of sotrovimab. Results A total of 634 patients were included (63.4% aged < 65 years; 50.3% male). A high proportion (67.7%; n = 429/634) of patients were immunocompromised, with 36.9% (n = 234/634) actively treated for malignancy. During the 29-day acute period, 12.5% (n = 79/634) of sotrovimab-treated patients were hospitalised due to any cause (median duration 4 days; median time to hospitalisation 14 days) and 1.1% (n = 7/634) died due to any cause. The proportion of sotrovimab-treated patients experiencing COVID-19-related hospitalisation was highest during the Delta predominance and Delta/BA.1 codominance (both 6.3%) periods. During the BA.1 predominance, BA.1/BA.2 codominance and BA.2/BA.5 codominance periods, COVID-19-related hospitalisations were consistently low (all ≤2.7%). Conclusion This study indicated low rates of COVID-19-related hospitalisations and all-cause deaths in sotrovimab-treated patients in Belgium, including during Omicron subvariant periods, despite over two-thirds of the study population being immunocompromised.

Atrial fibrillation fact sheet in Korea 2024: part 2—stroke prevention in Korean patients with atrial fibrillation

ObjectiveAtrial fibrillation (AF) increases the risk of thromboembolic events, making oral anticoagulants (OACs) essential for high-risk patients. This fact sheet provides nationwide statistics on AF management for stroke prevention in Korea. We aimed to evaluate current anticoagulation treatment trends and strategies in Korea.MethodThe Korean national health claims database from the National Health Insurance Service was used. AF patients aged ≥ 18 years from 2013 to 2022 were included. OAC use, including warfarin and non-vitamin K antagonist OACs (NOACs), was tracked through prescription data. The rates of OAC use were calculated based on continued use, considering prescription dates and amounts. For patients with multiple encounters, the last encounter was used for analysis.ResultsDuring the study, 20.4% of strokes were accompanied by AF, with AF diagnosed within 6 months before or after the stroke. The number of patients diagnosed with AF after a stroke increased from 4893 in 2013 to 6978 in 2022. Among newly diagnosed AF patients requiring OACs, 51% were not prescribed OACs within 6 months. OAC treatment rates for high-risk AF patients increased from 44.6% in 2013 to 77.5% in 2022, with NOAC prescriptions rising significantly after 2015. Regional variations in OAC prescription rates were observed, with lower rates in suburban/rural areas than in urban regions (76.0% vs. 79.6%, p < 0.001).ConclusionsConsiderable strokes could have been prevented with earlier AF detection and OAC treatment through more intensive electrocardiogram screening.

Prognostic Value of Fatty Acid Metabolism-related Genes in Patients with Bladder Cancer.

This study aimed to explore the expression profiles of fatty acid metabolism- related genes (FAMRGs) in patients with bladder cancer (BLCA). The corresponding clinicopathological features of BLCA patients and RNA sequencing data were downloaded from TCGA and GSE13507. Univariate Cox regression was used to determine the prognostic value of FRGS in BLCA patients. LASSO regression analysis was then performed to select potential risk genes and eliminate genes that might overfit the model. Based on the independent prognostication-related FRGs, the nomogram survival model was established using the root mean square value of the R packet to predict the 1-year, 3-year, and 5-year survival rates of BLCA patients. By determining the area under the curve (AUC) value, the time-dependent receiver operating characteristic curve (ROC) was used to evaluate the prognostic efficiency of our model. A total of 243 DEFRGs were identified. Twenty FRGs were found to be related to the prognosis of BLCA in the TCGA database. Survival curves showed that high-risk patients had significantly shorter OS than low-risk cases (p < 0.001). The AUC of risk was 0.784, which was superior to age, sex, and stage, suggesting that the risk score was more favorable in predicting OS than traditional pathologic prognostic factors. The AUC was 0.757 at 1 year, 0.732 at 3 years, and 0.733 at 5 year-OS. In this study, we demonstrated that a FAMRG prognosis biomarker is associated with the tumor immune microenvironment in patients with BLCA.

Patient-centric comparative analysis of experiences in open upright and conventional closed MRI scanners

IntroductionMRI often induces anxiety, leading to incomplete scans and claustrophobia-related distress. Open MRI systems aim to enhance patient comfort. This study examines how prior MRI experiences impact subsequent encounters in an open upright MRI scanner. MethodsIn this cross-sectional study, 118 adult patients completed a self-administered questionnaire from August 2022 to October 2023. It covered previous MRI experiences, including questions about claustrophobia, premature scan terminations, sedative medication usage, general MRI experiences, and interactions with radiology technologists. ResultsPatients in open upright MRI reported less claustrophobia compared to closed MRI systems (18.4% vs. 58.3%), fewer premature scan terminations (5.3% vs. 31.0%), and less sedative use (5.3% vs. 46.9%). Moderate positive correlations were found between past and current claustrophobic events and premature scan terminations. Effective communication with radiology technologists was essential for patient comfort and reduced claustrophobia. Scan duration and noise triggered discomfort in 26.1% and 21.6% of study participants respectively. Persons without prior MRI experience were more satisfied with the examination and expressed no clear preference for future MRI settings, contrasting those with previous exposure favoring the open MRI setup. ConclusionThe study emphasizes the benefits of open upright MRI for high-risk claustrophobic patients. It identifies the lasting impact of negative MRI experience on future examinations and highlights the crucial role of radiology technologists. Implications for practiceIntegrating open MRI scanners in medical facilities and prioritizing effective communication with radiology technologists enhances patient comfort. Positive experiences with open MRI may improve patient compliance and offer greater flexibility for future examinations.

Ga68-PSMA PET for lymph node staging in intermediate and high-risk prostate cancer patients undergoing robotic assisted radical prostatectomy.

In intermediate/high risk prostate cancer, preoperative staging exams are mandatory. The aim of these imaging studies is to evaluate eventual lymph nodes involvement and/or metastatic spread of the tumor. Nevertheless, computed tomography (CT), magnetic resonance imaging (MRI), bone scan modalities have controversial sensitivity. Introduction of PET-PSMA and its use also as preoperative exam, seems to improve diagnostic accuracy due to favorable negative predictive value. The aim of this study was to evaluate the accuracy of PET-PSMA as a preoperative staging exam and its accuracy in predicting lymph nodes involvement in intermediate/high risk prostate cancer (PCa) patients. A retrospective analysis of 50 patients diagnosed with intermediate/high risk PCa between 2018 and 2022 has been performed. All patients underwent preoperative 68Ga-PSMA PET/CT prior to robot-assisted radical prostatectomy (RARP) + extended pelvic lymph node dissection (ePLND). The cohort was categorized into two groups: pathologically negative lymph nodes (pN0) vs. positive nodes (pN1). A descriptive and comparative analysis was conducted. Correlation analysis between continuous variables was performed using the Spearman's Rank Test. Using lymph nodes histopathological results as reference standard, the diagnostic performance of 68Ga-PSMA PET/CT was calculated. Overall, 50 patients were included. The mean age was 63.3 years with a median prostatic specific antigen (PSA) of 7.7 ng/dL. Forty-four percent of the patients exhibited an International Society of Urological Pathology (ISUP) score of 4 or higher, and 28% had a pT3 stage. Overall, 43 (86%) patients submitted to ePLND did not present lymph node metastases (pN0), while 8 (14%) patients were pN1. PET-PSMA showed low sensitivity in detecting lymph node metastases (25%) while a high specificity in excluding lymph-node disease (88.1%) has been observed. Finally, we noted a significant positive correlation between the total SUV<inf>max</inf> of the prostate and the initial total PSA (r=0.38; P=0.019), as well as the percentage of tumor involvement (r=0.383; P=0.022). Evidence on the role of PET-PSMA in the primary staging of PCa is steadily building up. A positive correlation between SUV and prostate involvement indicates that PET-PSMA could reflect, with a good approximation, the pathological features of the prostate. However, the low sensitivity depicted remains the main limitation. Future prospective studies are needed to determine the impact on patient outcome.

The modified 5-item frailty index as a predictor of perioperative risk in patients undergoing percutaneous nephrolithotomy.

The modified 5-item frailty index is a relatively new tool to assess the post-operative complication risks. In urology, there is limited literature on the impact of frailty on percutaneous nephrolithotomy (PCNL) outcomes. We aimed to compare the predictive value of the modified 5-item frailty index (mFI-5) to identify high risk patients prior to PCNL. A database of patients undergoing PCNL, between 2015 and 2022, was analyzed. Patient frailty was assessed using the mFI-5 index. The mFI-5 index was calculated based on the presence of the five co-morbidities: congestive heart failure within 30days prior to surgery, diabetes mellitus, chronic obstructive pulmonary disease, partially dependent or totally dependent functional health status at time of surgery, and hypertension requiring medication. Patients were grouped as not frail (mFI-5 = 0), intermediate (mFI-5 = 1), and severely frail (mFI-5 ≥ 2). Primary outcomes were 30-day postoperative complications. Secondary outcomes were hospitalization: total hospital length of stay, reoperation, and unplanned readmission. From a total of 320 PCNL patients included for analysis, 54.06% (n = 173) were not frail, 17.81% (n = 57) were intermediate, and 28.12% (n = 90) were severely frail. Frail patients were likely to be older (p = 0.002) and have a higher American Society of Anesthesiologists score (p = 0.001), chronic kidney disease (p < 0.001). Patients of intermediate or severe frailty were more likely to exhibit postoperative sepsis (p = 0.042), significant blood loss (p = 0.036) and require intensive care units admissions (p = 0.0015). Frail patients had a longer hospital length of stay (p < 0.001) and tended to require reoperation (p = 0.001), and unplanned readmission (p = 0.02). Frailty assessment appears useful in stratifying those at risk of extended hospitalization, septic and hemorrhagic complications, readmission, or reoperation after PCNL. Preoperative assessment of frailty phenotype may give insight into treatment decisions and assist surgeons in counselling patients on expected course and hospital stay following PCNL.

How Primary Care Intensive Management Supports Coordinated Care for High-Risk Patients

How Primary Care Intensive Management Supports Coordinated Care for High-Risk Patients

How Primary Care Intensive Management Supports Coordinated Care for High-Risk Patients

How Primary Care Intensive Management Supports Coordinated Care for High-Risk Patients

Optimal hyperglycemia thresholds in patients undergoing chemotherapy: a cross sectional study of oncologists' practices.

Neither the United States nor the European oncology guidelines include details for appropriate management of hyperglycemia in cancer patients. The aim was to identify fasting and random blood glucose thresholds, and hemoglobin A1c (HbA1c) targets used by oncologists in clinical practice when managing hyperglycemia in patients with cancer undergoing chemotherapy. This national, crosssectional study utilized a questionnaire to collect oncologists' perceptions about optimal blood glucose thresholds and HbA1c targets in patients with cancer undergoing chemotherapy. Descriptive statistics were calculated to summarize glucose thresholds, HbA1c targets, and sample characteristics. Responses to an open-ended question about oncologists' approach to hyperglycemia management were analyzed via thematic analysis using an inductive approach. Respondents (n = 229) were on average 52.1years of age, 67.7% men, and 91.3% White. For patients without diabetes but experiencing hyperglycemia, oncologists targeted lower and upper fasting blood glucose levels between 75-121mg/dL and 105-135mg/dL, respectively. For patients with diabetes, the targets for lower and upper fasting blood glucose levels ranged between 100-130mg/dL and 128-150mg/dL, respectively. Fasting blood glucose (95.6%) and HbA1c (78.6%) were the most commonly used clinical indicators to consider chemotherapy dose reduction, delay, or discontinuation due to hyperglycemia in patients receiving chemotherapy with curative intent. Among those receiving palliative intent chemotherapy, the preferred clinical parameters were random blood glucose (90.0%), patient-reported blood glucose readings (70.7%), continuous glucose monitoring readings (65.1%), and patient-reported symptoms of hyperglycemia (65.1%). Three main themes emerged about oncologists' approach to hyperglycemia management: 1) identification of high-risk patients; 2) need for early identification, screening, and diagnosis of hyperglycemia; and 3) multiple hyperglycemia management strategies. Oncologists reported a wide variation of target blood glucose ranges considered appropriate in patients undergoing chemotherapy. Lack of clear guidance for hyperglycemia management during chemotherapy in the United States may be contributing to a lack of consistency in clinical practice.

The option of transosseous distal suture placement during minimally invasive Achilles tendon repair for high-risk patients can improve outcomes, however does not prevent re-rupture

PurposeAchilles tendon ruptures (ATRs) close to the insertion, in high-level athletes, and in patients at high risk of re-rupture, may be better suited to operative repair. Minimally Invasive Repair (MIR) of the Achilles tendon has excellent outcome and low complication rates. Traditionally MIR has showed lower repair strength, failing due to suture pull-out from the distal tendon stump. The aim of this study was to describe the outcome of ATR patients who received transosseous distal suture placement using a standard technique as a reference.MethodsFollowing ATR, patients were evaluated for pre-injury activity level, body weight, location of the tear and size of the distal Achilles tendon stump. Patients considered to be at high-risk of re-rupture: Tegner level ≥ 8, body weight ≥ 105Kg and distal ATR, received transosseous (TO) distal suture placement (n = 20) rather than the usual transtendinous (TT) technique (n = 55). Patient reported outcome measures and functional evaluation was performed at 12 months following repair.ResultsAt 12 months follow up both methods resulted in good median (IQR) Achilles tendon Total Rupture Score TO 83.8 (74-88.3) vs. TT 90 (79–94), low increased relative Achilles Tendon Resting Angle TO -3.5˚ (3.6) vs. TT -3.5˚ (3.3) and mean (SD) Single leg Heel-Rise Height Index TO 88.2% (9.9) vs. TT 85.6% (9.9) (n.s.). There were 4 re-ruptures in the high-risk group and 2 in the group receiving TT distal suture placement. All but one of these were traumatic in nature. The mode of failure following TO distal suture placement was proximal suture pull out.ConclusionsTo distal suture placement during minimally-invasive Achilles tendon repair for higher-risk patients can lead to results equivalent to those in lower-risk patients treated with a standard TT MIR technique, except for the re-rupture rate which remained higher. There may be factors that have greater influence on outcome other than suture placement following ATR.

Single-molecule epiallelic profiling of DNA derived from routinely collected Pap specimens for noninvasive detection of ovarian cancer.

Recent advances in molecular analyses of ovarian cancer have revealed a wealth of promising tumour-specific biomarkers, including protein, DNA mutations and methylation; however, reliably detecting such alterations at satisfactorily high sensitivity and specificity through low-cost methods remains challenging, especially in early-stage diseases. Here we present PapDREAM, a new approach that enables detection of rare, ovarian-cancer-specific aberrations of DNA methylation from routinely-collected cervical Pap specimens. The PapDREAM approach employs a microfluidic platform that performs highly parallelized digital high-resolution melt to analyze locus-specific DNA methylation patterns on a molecule-by-molecule basis at or near single CpG-site resolution at a fraction (<1/10th) of the cost of next-generation sequencing techniques. We demonstrate the feasibility of the platform by assessing intermolecular heterogeneity of DNA methylation in a panel of methylation biomarker loci using DNA derived from Pap specimens obtained from a cohort of 43 women, including 18 cases with ovarian cancer and 25 cancer-free controls. PapDREAM leverages systematic multidimensional bioinformatic analyses of locus-specific methylation heterogeneity to improve upon Pap-specimen-based detection of ovarian cancer, demonstrating a clinical sensitivity of 50% at 99% specificity in detecting ovarian cancer cases with an area under the receiver operator curve of 0.90. We then establish a logistic regression model that could be used to identify high-risk patients for subsequent clinical follow-up and monitoring. The results of this study support the utility of PapDREAM as a simple, low-cost screening method with the potential to integrate with existing clinical workflows for early detection of ovarian cancer. KEY POINTS: We present a microfluidic platform for detection and analysis of rare, heterogeneously methylated DNA within Pap specimens towards detection of ovarian cancer. The platform achieves high sensitivity (fractions <0.00005%) at a suitably low cost (∼$25) for routine screening applications. Furthermore, it provides molecule-by-molecule quantitative analysis to facilitate further study on the effect of heterogeneous methylation on cancer development.

A Six-gene Prognostic Model Based on Neutrophil Extracellular Traps (NETs)-related Gene Signature for Lung Adenocarcinoma.

Lung adenocarcinoma (LUAD) is one of the most common malignant cancers. Neutrophil extracellular traps (NETs) have been discovered to play a crucial role in the pathogenesis of LUAD. We aimed to establish an innovative prognostic model for LUAD based on the distinct expression patterns of NETs-related genes. The TCGA LUAD dataset was utilized as the training set, while GSE31210, GSE37745, and GSE50081 were undertaken as the verification sets. The patients were grouped into clusters based on the expression signature of NETs-related genes. Differentially expressed genes between clusters were identified through the utilization of the random forest and LASSO algorithms. The NETs score model for LUAD prognosis was developed by multiplying the expression levels of specific genes with their corresponding LASSO coefficients and then summing them. The validity of the model was confirmed by analysis of the survival curves and ROC curves. Additionally, immune infiltration, GSEA, mutation analysis, and drug analysis were conducted. Silencing ABCC2 in A549 cells was achieved to investigate its effect. We identified six novel NETs-related genes, namely UPK1B, SFTA3, GGTLC1, SCGB3A1, ABCC2, and NTS, and developed a NETs score signature, which exhibited a significant correlation with the clinicopathological and immune traits of the LUAD patients. High-risk patients showed inhibition of immune-related processes. Mutation patterns exhibited variability among the different groups. AZD3759, lapatinib, and dasatinib have been identified as potential candidates for LUAD treatment. Moreover, the downregulation of ABCC2 resulted in the induction of apoptosis and suppression of migration and invasion in A549 cells. Altogether, this study has identified a novel NET-score signature based on six novel NET-related genes to predict the prognosis of LUAD and ABCC2 and has also explored a new method for personalized chemo-/immuno-therapy of LUAD.

Construction of a Risk Prediction Model for the Occurrence of Acute Skin Failure in Critically Ill Patients: A Prospective Study.

The risk factors for acute skin failure (ASF), a serious complication of the skin, are not fully understood. This study was designed to explore the risk factors for ASF in critically ill patients and construct a clinical prediction model. Intensive care unit patients were prospectively observed and assigned into two groups: with and without ASF. A logistic regression model was constructed, and its predictive power and clinical utility were evaluated. Of the 204 eligible patients enrolled as participants, 58 (28.43%) developed ASF. Sepsis, vasoactive drugs, and age were shown to be risk factors for ASF, whereas peripheral perfusion index ratio and albumin level were shown to be protective factors. The area under the receiver operating characteristic curve was 0.83. The maximum Youden index of the model was 0.39 (specificity: 0.87, sensitivity: 0.77). The Hosmer-Lemeshow test (p = .20) and calibration curve showed good fitness and predictive utility with respect to the model. The developed model effectively predicts ASF risk, allowing for the early identification of high-risk patients. Identifying risk factors such as sepsis, vasoactive drugs, and age and considering protective factors such as peripheral perfusion index and albumin levels may help optimize care plans. Clinical staff should pay special attention to these factors and their impact on skin health in critically ill patients.

Venous Thromboembolism Prophylaxis in High-Risk Pediatric Trauma Patients.

The indications, safety, and efficacy of chemical venous thromboembolism prophylaxis (cVTE) in pediatric trauma patients remain unclear. A set of high-risk criteria to guide cVTE use was recently recommended; however, these criteria have not been evaluated prospectively. To examine high-risk criteria and cVTE use in a prospective multi-institutional study of pediatric trauma patients. This cohort study was completed between October 2019 and October 2022 in 8 free-standing pediatric hospitals designated as American College of Surgeons level I pediatric trauma centers. Participants were pediatric trauma patients younger than 18 years who met defined high-risk criteria on admission. It was hypothesized that cVTE would be safe and reduce the incidence of VTE. Receipt and timing of chemical VTE prophylaxis. The primary outcome was overall VTE rate stratified by receipt and timing of cVTE. The secondary outcome was safety of cVTE as measured by bleeding or other complications from anticoagulation. Among 460 high-risk pediatric trauma patients, the median (IQR) age was 14.5 years (10.4-16.2 years); 313 patients (68%) were male and 147 female (32%). The median (IQR) Injury Severity Score (ISS) was 23 (16-30), and median (IQR) number of high-risk factors was 3 (2-4). A total of 251 (54.5%) patients received cVTE; 62 (13.5%) received cVTE within 24 hours of admission. Patients who received cVTE after 24 hours had more high-risk factors and higher ISS. The most common reason for delayed cVTE was central nervous system bleed (120 patients; 30.2%). There were 28 VTE events among 25 patients (5.4%). VTE occurred in 1 of 62 patients (1.6%) receiving cVTE within 24 hours, 13 of 189 patients (6.9%) receiving cVTE after 24 hours, and 11 of 209 (5.3%) who had no cVTE (P = .31). Increasing time between admission and cVTE initiation was significantly associated with VTE (odds ratio, 1.01; 95% CI, 1.00-1.01; P = .01). No bleeding complications were observed while patients received cVTE. In this prospective study, use of cVTE based on a set of high-risk criteria was safe and did not lead to bleeding complications. Delay to initiation of cVTE was significantly associated with development of VTE. Quality improvement in pediatric VTE prevention may center on timing of prophylaxis and barriers to implementation.