High-risk Patients Research Articles

Optimal timing of revascularization for patients with non-ST segment elevation myocardial infarction and severe left ventricular dysfunction.

Optimal timing of revascularization for patients who presented with non-ST segment elevation myocardial infarction (NSTEMI) and severe left ventricular (LV) dysfunction is unclear. A total of 386 NSTEMI patients with severe LV dysfunction from the nationwide, multicenter, and prospective Korea Acute Myocardial Infarction Registry V (KAMIR-V) were enrolled. Severe LV dysfunction was defined as LV ejection fraction ≤ 35%. Patients with cardiogenic shock were excluded. Patients were stratified into two groups: PCI within 24 hours (early invasive group) and PCI over 24 hours (selective invasive group). Primary endpoint was major adverse cardiac and cerebrovascular events (MACCE) including all-cause death, non-fatal MI, repeat revascularization, and stroke at 12 months after index procedure. Early invasive group showed higher incidence of in-hospital death (9.4% vs 3.3%, P = .036) and cardiogenic shock (11.5% vs 4.6%, P = .030) after PCI. Early invasive group also showed higher maximum troponin I level during admission (27.7 ± 44.8 ng/mL vs 14.9 ± 24.6 ng/mL, P = .001), compared with the selective invasive group. Early invasive group had an increased risk of 12-month MACCE, compared with selective invasive group (25.6% vs 17.1%; adjusted HR = 2.10, 95% CI 1.17-3.77, P = .006). Among NSTEMI patients with severe LV dysfunction, the early invasive strategy did not improve the clinical outcomes. This data supports that an individualized approach may benefit high-risk NSTEMI patients rather than a routine invasive approach.

Effect analysis of 847 nasopharyngeal carcinoma cases treated with intensity modulated radiation: Experience and suggestions

ObjectivesTo identify the failure patterns and prognostic factors of nonmetastatic nasopharyngeal carcinoma (NPC) in the intensity-modulated radiotherapy (IMRT) era. MethodsData on 847 patients with newly diagnosed, non-disseminated NPC treated by IMRT between 2012 and 2016 were retrospectively reviewed. Survival outcome, failure patterns and prognosis factors were analyzed. ResultsThe 5-year local relapse-free survival, nodal relapse-free survival, distant metastasis-free survival, disease-free survival, and overall survival rates were 94.3%, 95.3%, 84.8%, 76.5% and 85.7%, respectively. The major local recurrence sites were the nasopharynx (91.5%, 43/47) and skull base (68.1%, 32/47); 39 patients had in-field failures, four had marginal failures, and four had out-field failures. Level IIb (62.2%, 23/37) was the most frequent regional recurrence site, followed by IIa (35.1%, 13/37) and retropharyngeal region (32.4%, 12/37); 35 cases had in-field failure alone, one had out-field failure alone, and one had both in- and out-field failure. TNM stage was the most significant factor for prognosis prediction. 402 (47.5%) patients had acute adverse events of grade 3 or 4; leukopenia (31.5%) and mucositis (26.7%) was the most common hematological and non-hematological event, respectively. Late complications were slight or moderate damages; xerostomia (647/847, 76.4%) and hearing impairment (422/847, 49.8%) remained the most troublesome. ConclusionNPC patients treated with IMRT obtained satisfactory survival outcomes. The key failure pattern was distant metastasis. The main pattern of local–regional failure was in-field failure. Screening high risk patients with distant metastases and optimizing radiotherapy targets should be studied.

Rationale and design of RESILIENCE: A prospective randomized clinical trial evaluating remote ischaemic conditioning for the prevention of anthracycline cardiotoxicity.

There is a lack of therapies able to prevent anthracycline cardiotoxicity (AC). Remote ischaemic conditioning (RIC) has shown beneficial effects in preclinical models of AC. REmote iSchemic condItioning in Lymphoma PatIents REceiving ANthraCyclinEs (RESILIENCE) is a multinational, prospective, phase II, double-blind, sham-controlled, randomized clinical trial that evaluates the efficacy and safety of RIC in lymphoma patients receiving anthracyclines. Patients scheduled to undergo ≥5 chemotherapy cycles including anthracyclines and with ≥1 AC-associated risk factors will be randomized to weekly RIC or sham throughout the chemotherapy period. Patients will undergo three multiparametric cardiac magnetic resonance (CMR) studies, at baseline, after the third cycle (intermediate CMR), and 2 months after the end of chemotherapy. Thereafter, patients will be followed up for clinical events over an anticipated median of ≥24 months. The primary endpoint is the absolute change from baseline in CMR-based left ventricular ejection fraction (LVEF). The main secondary outcome is the incidence of AC events, defined as (1) a drop in CMR-based LVEF of ≥10 absolute points, or (2) a drop in CMR-based LVEF of ≥5 and <10 absolute points to a value <50%. Intermediate CMR will test the ability of T2 mapping to predict AC versus classical markers (left ventricular strain and cardiac injury biomarkers). A novel CMR sequence allowing ultrafast cine acquisition will be validated in this vulnerable population. The RESILIENCE trial will test RIC (a novel non-invasive intervention to prevent AC) in a cohort of high-risk patients. The trial will also test candidate markers for their capacity to predict AC and will validate a novel CMR sequence reducing acquisition time in a vulnerable population.

Disease severity and activity in bronchiectasis: A paradigm shift in bronchiectasis management.

Bronchiectasis has an increasing prevalence and substantial clinical and economic burden. Therefore, physicians should identify patients with bronchiectasis at high risk of disease progression to ensure optimal management in advance. The heterogeneity of bronchiectasis means it is unlikely that any single parameter could identify high-risk patients, therefore disease severity is usually assessed using validated composite tools, such as the Bronchiectasis Severity Index, FACED, and Bronchiectasis Aetiology Comorbidity Index, to predict long-term outcomes in bronchiectasis. Disease severity, however, implies an advanced process with lung destruction. Earlier intervention may prevent disease progression and improve outcomes. To identify patients at risk, rather than patients with established advanced disease, we need to shift our focus from disease severity to disease activity. Disease activity denotes the activation level of underlying pathophysiological processes and can be measured using clinical presentations and biomarkers. This review discusses a paradigm shift in bronchiectasis management, focusing on disease activity rather than severity, to prevent disease progression.

The Impact of Preoperative Psychiatric Intervention for Postoperative Delirium after Major Oral and Maxillofacial Surgery with Free Flap Reconstruction

BackgroundPostoperative delirium (POD) is a severe complication associated with various adverse outcomes, especially in older patients. Although the incidence and risk factors for POD have been explored in general surgery, they have not been fully elucidated. Early identification of high-risk patients and active preoperative intervention are considered essential for the prevention of POD. Recently, psychiatric consultation intervention have been shown to prevent delirium. This study investigated the effect of preoperative psychiatric interventions on preventing POD in our specific surgical context. Materials and MethodsThis retrospective, single-center observational study included 86 patients who underwent major oral and maxillofacial surgery with free flap reconstruction between 2016 and 2023. The effect of psychiatric intervention were compared between patients with and without delirium. ResultsPreoperative psychiatric intervention did not reduce the incidence of POD. The incidence of POD was 29.1%. Univariate analyses showed no significant associations between POD and any clinical variables. ConclusionThere was no difference in the incidence of POD between patients who received preoperative psychiatric intervention and those who did not, and further investigation is needed to determine the efficacy of preoperative psychiatric intervention in the prevention of POD.

Construction of a prognostic model for disulfidptosis-related long noncoding RNAs in R0 resected hepatocellular carcinoma and analysis of their impact on malignant behavior

BackgroundDisulfidptosis is an emerging form of cellular death resulting from the binding of intracellular disulfide bonds to actin cytoskeleton proteins. This study aimed to investigate the expression and prognostic significance of hub disulfidptosis-related lncRNAs (DRLRs) in R0 resected hepatocellular carcinoma (HCC) as well as their impact on the malignant behaviour of HCC cells.MethodsA robust signature for R0 resected HCC was constructed using least absolute shrinkage and selection operator (LASSO) and multivariate Cox regression and was validated in an independent internal validation cohort to predict the prognosis of R0 HCC patients. Comprehensive bioinformatics analysis was performed on the hub DRLRs (KDM4A-AS1, MKLN1-AS, and TMCC1-AS1), followed by experimental validation using quantitative real-time polymerase chain reaction (qRT‒PCR) and cellular functional assays.ResultsThe signature served as an independent prognostic factor applicable to R0 HCC patients across different age groups, tumour stages, and pathological characteristics. Gene Ontology (GO) and gene set enrichment analysis (GSEA) revealed hub pathways associated with this signature. The high-risk group presented an increased abundance of M0 macrophages and activated memory CD4 T cells as well as elevated macrophage and major histocompatibility complex (MHC) class I expression. High-risk R0 HCC patients also presented increased tumour immune dysfunction and exclusion scores (TIDEs), mutation frequencies, and tumour mutational burdens (TMBs). Drug sensitivity analysis revealed that high-risk patients were more responsive to drugs, including GDC0810 and osimertinib. High expression levels of the three hub DRLRs were detected in R0 HCC tissues and HCC cell lines. Functional assays revealed that the three hub DRLRs enhanced HCC cell proliferation, migration, and invasion.ConclusionsA signature was constructed on the basis of three DRLRs, providing novel insights for personalized precision therapy in R0 HCC patients.Graphical

Assessment of the effectiveness of a polypropylene onlay mesh in the prevention of laparoscopic trocar-site incisional herniain high-risk patients. A randomized clinical trial.

Trocar site incisional hernia (TSIH) is a common complication of laparoscopic surgery. In the scientific literature there are few descriptions of methods or tools for its prevention. The aim of this report was to assess the effectiveness and safety of a prophylactic measure designed to lower rates of TSIH. A multicenter randomized double-blinded clinical trial was performed in high-risk patients (diabetes mellitus and/or age ≥ 70years and/or BMI ≥ 30kg/m2 and/or extended incision for specimen retrieval) who underwent either elective or emergency laparoscopic cholecystectomy. Patients were assigned to prophylactic onlay polypropylene mesh fixation (intervention) or to standard trocar closure (control). The main aim was to analyze the efficacy of the intervention, taking occurrence of TSIH as the primary outcome. Clinical and radiological follow up lasted at least one year after surgery. Secondary endpoints were technique-related complications (surgical site occurrences). One hundred and forty-three patients were randomized and finally 116 were analyzed (64 in the intervention arm and 52 in the control arm). Groups were homogeneous. Mean [SD] age, 65 [18] years; 86 (60.6%) were women. The cumulative TSIH incidence was lower in the intervention group although the differences did not reach statistical significance, assessed either radiologically (16 [25.4%] vs 17 [31.5%], p = 0.538) or clinically (9 [16.1%] vs 9 [20], p = 0.613). No differences in surgical site infection, hematoma or seroma were detected. Mean follow-up was 670days (range 223-1294). Our results show that, when properly assessed, the overall TSIH incidence is extremely high. Although polypropylene onlay mesh placement is safe, it does not appear to be effective in reducing the TSIH incidence rate. Radiological evaluation may be more accurate. ClinicalTrials.org NCT03495557. Date of registration: April 12, 2018.

Association of the vitamin D metabolism gene polymorphism with the severity of coronary lesions assessed by SYNTAX score

This study aimed to determine the association of vitamin D serum blood levels and vitamin D gene polymorphism with the severity of coronary lesions in patients with stable coronary artery disease (CAD). Material and methods. 260 patients with stable CAD (average age was 58 years) were examined in the presented research. All patients were divided into two groups according to the SYNTAX score: low-risk patients with SYNTAX score ≤ 31 (n = 224) and high-risk patients with SYNTAX score &gt; 31 (n = 36). For enzyme-linked immunosorbent assay and genetic analysis, peripheral blood was collected from the cubital vein into vacuum tubes containing coagulation activator and K3-EDTA, respectively. Serum blood level of 25-hydroxyvitamin D (DiaSource Diagnostics, Belgium) and 1,25-dihydroxyvitamin D (Immunodiagnostic Systems, Great Britain) were determined by enzyme-linked immunosorbent assay according to the manufacturers’ protocols. Genomic DNA was isolated by phenol-chloroform extraction method from whole blood. The quality and quantity of isolated DNA were assessed using NanoDrop spectrophotometer (Thermo Fisher Scientific, USA). Five polymorphic variants in the VDR (rs2228570 and rs73123) and GC (rs7041, rs1155563 and rs2298849) genes were selected for analysis. Genotyping was performed by real-time PCR in a 96-well plate with fluorescently labeled TaqMan probes. The quality of PCR was controlled by repeated genotyping of 10 % of the analyzed samples. Results. We found no statistically significant differences in serum blood level of the studied markers in patients from low-risk and high-risk groups. One polymorphic variant in the GC gene associated with the multiple coronary lesions (rs2298849) (odds ratio 2.26, 95 % confidence interval 1.28–3.99, p = 0.006) according to an additive inheritance model was identified. In addition, we determined the association between low serum blood level of 1,25-dihydroxyvitamin D in patients with CAD with multiple lesions of the coronary vascular system with A/A – A/G genotypes of the rs2228570 polymorphism in the VDR gene, A/A genotype of the rs7041 polymorphism and A/A genotype of the rs2298849 polymorphism in the GC gene. Conclusions. Allelic variants in the vitamin D metabolism genes are associated with the degree of coronary artery lesions assessed by the SYNTAX score in patients with stable CAD. Also, serum blood level of the active form of vitamin D (1,25-dihydroxyvitamin D) is less in carriers of homozygous genotypes for the major alleles of the VDR and GC genes.

Carbapenem resistance in Enterobacterales: Predicting clinical outcomes in bloodstream infections

PurposeCarbapenem-resistant Enterobacterales (CRE) are a global concern due to their high mortality rates and limited therapeutics. CRE-caused bloodstream infections (BSIs) are challenging to manage, especially in healthcare settings. This study aimed to investigate the predictors of mortality in BSI patients caused by CRE. MethodsA single center prospective study to examine the characteristics of BSI caused by CRE in a large academic hospital over 15 months. The main outcomes were microbiological characteristics and clinical outcomes of patients at 28 days based on a step-wise regression analysis. ResultsA total of 76 episodes of BSI due to CRE were included. The study found that the most common type of carbapenemase was OXA-48 (69.7 %, n = 53), followed by the co-existence of OXA-48 and MBL (26.3 %, n = 20), with Klebsiella pneumoniae being the most common (90 %, n = 69). Patients with OXA-48-BSI were more likely to have a urinary source of infection, while patients with MBL-BSI were more likely to have a non-urinary source of infection. All cases (100 %) had medical devices. Around 30.3 % of patients received effective empirical treatment, while 61.8 % received adequate therapy at 48 h. The overall mortality rate was 42.1 % (n = 32), and the main predictors of mortality in this study were the presence of sepsis and inadequate initial therapy, while age >65 predicted mortality in the linear regression but not the stepwise regression model. ConclusionCRE-BSIs are a serious health threat. The study highlights the need for preventive strategies focused on high-risk patients and proper device management to reduce BSI.

Identification of immunity- and ferroptosis-related signature genes as potential design targets for mRNA vaccines in AML patients.

Immune-associated ferroptosis plays an important role in the progression of acute myeloid leukemia (AML); however, the targets that play key roles in this process are currently unknown. This limits the development of mRNA vaccines based on immune-associated ferroptosis for clinical therapeutic applications. In this study, based on the rich data resources of the TCGA-LAML cohort, we analyzed the tumor mutational burden (TMB), gene mutation status, and associations between immune and ferroptosis genes to reveal the disease characteristics of AML patients. To gain a deeper understanding of differentially expressed genes, we applied the Limma package for differential expression analysis and integrated data sources such as ImmPort Shared Data and FerrDb V2. Moreover, we established gene modules related to TMB according to weighted gene coexpression network analysis (WGCNA) and explored the functions of these modules in AML and their relationships with TMB. We focused on the top 30 most frequent genes through a detailed survey of missense mutations and single nucleotide polymorphisms (SNPs) and selected potentially critical gene targets for subsequent analysis. Based on the expression of these genes, we successfully subgrouped AML patients and found that the subgroups associated with TMB (C1 and C2) exhibited significant differences in survival. The differences in the tumor microenvironment and immune cells between C1 and C2 patients were investigated with the ESTIMATE and MCP-counter algorithms. A predictive model of TMB-related genes (TMBRGs) was constructed, and the validity of the model was demonstrated by categorizing patients into high-risk and low-risk groups. The differences in survival between the high-risk patients and high-TMB patients were further investigated, and potential vaccine targets were identified via immune cell-level analysis. The identification of immunity- and ferroptosis-associated signature genes is an independent predictor of survival in AML patients and provides new information on immunotherapy for AML.

Construction of a pathomics model for predicting mRNAsi in lung adenocarcinoma and exploration of biological mechanism

ObjectiveThis study aimed to predict the level of stemness index (mRNAsi) and survival prognosis of lung adenocarcinoma (LUAD) using pathomics model. MethodsFrom The Cancer Genome Atlas (TCGA) database, 327 LUAD patients were randomly assigned to a training set (n = 229) and a validation set (n = 98) for pathomics model development and evaluation. PyRadiomics was used to extract pathomics features, followed by feature selection using the mRMR-RFE algorithm. In the training set, Gradient Boosting Machine (GBM) was utilized to establish a model for predicting mRNAsi in LUAD. The model's predictive performance was evaluated using ROC curves, calibration curves, and decision curve analysis (DCA). Prognostic analysis was conducted using Kaplan-Meier curves and cox regression. Additionally, gene enrichment analysis, tumor microenvironment analysis, and tumor mutational burden (TMB) analysis were performed to explore the biological mechanisms underlying the pathomics prediction model. ResultsMultivariable cox analysis (HR = 1.488, 95 % CI 1.012–2.187, P = 0.043) identified mRNAsi as a prognostic risk factor for LUAD. A total of 465 pathomics features were extracted from TCGA-LUAD histopathological images, and ultimately, the most representative 8 features were selected to construct the predictive model. ROC curves demonstrated the significant predictive value of the model for mRNAsi in both the training set (AUC = 0.769) and the validation set (AUC = 0.757). Calibration curves and Hosmer-Lemeshow goodness-of-fit test showed good consistency between the model's prediction of mRNAsi levels and the actual values. DCA indicated a good net benefit of the model. The prediction of mRNAsi levels by the pathomics model is represented using the pathomics score (PS). PS was strongly associated with the prognosis of LUAD (HR = 1.496, 95 % CI 1.008–2.222, P = 0.046). Signaling pathways related to DNA replication and damage repair were significantly enriched in the high PS group. Prediction of immune therapy response indicated significantly reduced Dysfunction in the high PS group (P < 0.001). The high PS group exhibited higher TMB values (P < 0.001). ConclusionsThe predictive model constructed based on pathomics features can forecast the mRNAsi and survival risk of LUAD. This model holds promise to aid clinical practitioners in identifying high-risk patients and devising more optimized treatment plans for patients by jointly employing therapeutic strategies targeting cancer stem cells (CSCs).

An Evaluation of Oral Anticoagulant Safety Indicators by England’s Community Pharmacies

Background: Anticoagulants are life-saving medicines that can prevent strokes for patients diagnosed with atrial fibrillation (AF) as well as treating patients with venous thromboembolism (VTE), but when used incorrectly, they are frequently associated with patient harm. Aim: To evaluate the impact of community pharmacy teams on optimising patient knowledge and awareness and improving medication safety from the use of anticoagulants. Methods: Two national audits, consisting of 17 questions assessing and improving patients’ understanding of anticoagulant therapy, identifying high-risk patients, and contacting prescribers when clinically appropriate were incentivised for England’s community pharmacies in 2021–2022 and 2023–2024 using the Pharmacy Quality Scheme (PQS) commissioned by NHS England. Results: Approximately 11,000 community pharmacies audited just under a quarter of a million patients in total, whilst making almost 150,000 interventions for patients taking oral anticoagulants, i.e., identifying and addressing medication issues which could increase the risk of bleeding/harm. Out of the 111,195 patients audited in 2021–2022, only 24,545 (23%) patients were prescribed vitamin K antagonists. The remaining patients were prescribed direct oral anticoagulants (DOACs). By 2023–2024, this decreased to 17,043 (16%) patients. Most patients knew that they were prescribed an anticoagulant (95.6%, 106,255 in 2021–2022 and 96.5%, 101,006 in 2023–2024, p &lt; 0.001). Discussion: The audits resulted in a statistically significant increase in patients with a standard yellow anticoagulant alert card, as identified in audit 2 (73,901 66.5% in 2021–2022 to 76,735, 73.3% in 2023–2024, p &lt; 0.001). Furthermore, fewer patients were prescribed concurrent antiplatelets with an anticoagulant (6021; 4.6% in 2021–2022 to 4975; 4% in 2023–2024, p &lt; 0.001). Although there was an increase in the number of patients prescribed NSAIDs with anticoagulants, more of these patients were also prescribed gastroprotection concurrently (927 77.2% in 2021–2022 to 1457 84.1% in 2023–2024, p &lt; 0.05). The majority of patients on warfarin had their blood checked within 12 weeks. Further there was an increase for these patients in the percentage of people prescribed VKAs who knew dietary changes can affect their anticoagulant medicine (16,764 67.4% in 2021–2022 to 12,594 73.9% in 2023–2024 p &lt; 0.001). Conclusions: Community pharmacy teams are well placed in educating and counselling patients on the safe use of anticoagulants and ensuring that all patients are correctly monitored.

In-hospital mortality and its associated factors among hospitalized stroke patients at public hospitals of Eastern Ethiopia

BackgroundStroke is rapidly developing clinical signs of focal/ global disturbance of cerebral function, with symptoms lasting more than 24 h and leading to death. Data showed that stroke deaths in Ethiopia reached nearly seven percent of total deaths. Despite this report, there is a paucity of investigations about the problem.ObjectiveTo determine in-hospital mortality and its associated factors among hospitalized stroke patients in Hiwot Fana Comprehensive Specialized University Hospital and Jugal General Hospital, eastern Ethiopia from September 2016–August 2022 G.C.MethodsA retrospective cohort study was conducted among hospitalized stroke patients. A sample size of 395 medical records was selected from a total of 564 stroke patients by a simple random sampling technique. The data was analyzed by SPSS version 26 using bivariable and multivariable cox-regression models. A p-value of 0.05 and less at a 95% confidence interval was used to establish a statistically significant association.ResultsOf the total, 109 (27.6%) died in the hospital while 57.2% and 15.2% of them were discharged with improvement and against medical advice, respectively. Age greater than 65 (AHR = 4.71, 95% CI = 1.11–19.96), creatinine level > 1.2 mg/dl (AHR = 1.54, 95% CI = 1.0-2.39), and co-morbidity with atrial fibrillation (AHR = 1.48, 95% CI = 1.0-2.21) were significantly associated with in-hospital mortality.ConclusionIn-hospital mortality was found in more than a quarter of stroke patients. Mortality was more likely increased among the patients with age > 65, serum creatinine level > 1.2 mg/dl, and atrial fibrillation. Hence, these high-risk patients need to be monitored.

Prognostic factors and overall survival in pelvic Ewing's sarcoma and chordoma: A comparative SEER database analysis

BackgroundThis study aimed to develop and validate nomograms to predict overall survival (OS) for pelvic Ewing's sarcoma (EWS) and chordoma, identify prognostic factors, and compare outcomes between the two conditions. MethodsWe identified patients diagnosed with pelvic EWS or chordoma from the SEER database (2001–2019). Independent risk factors were identified using univariate and multivariate Cox regression analyses, and these factors were used to construct nomograms predicting 3-, 5-, and 10-year OS. Validation methods included AUC, calibration plots, C-index, and decision curve analysis (DCA). Kaplan-Meier curves and log-rank tests compared survival differences between low- and high-risk groups. ResultsThe study included 1175 patients (EWS: 611, chordoma: 564). Both groups were randomly divided into training (70 %) and validation (30 %) cohorts. OS was significantly higher for chordoma. Multivariate analysis showed year of diagnosis, income, stage, and surgery were significant for EWS survival, while age, time to treatment, stage, and surgery were significant for chordoma survival. Validation showed the nomograms had strong predictive performance and clinical utility. ConclusionsThe nomograms reliably predict overall survival (OS) in pelvic EWS and chordoma, helping to identify high-risk patients early and guide preventive measures. The study also found that survival rates are significantly higher for chordoma, highlighting different prognostic profiles between EWS and chordoma.

Establishment of a prognostic model for pancreatic cancer based on mitochondrial metabolism related genes

AimPancreatic ductal adenocarcinoma (PAAD) is recognized as an exceptionally aggressive cancer that both highly lethal and unfavorable prognosis. The mitochondrial metabolism pathway is intimately involved in oncogenesis and tumor progression, however, much remains unknown in this area. In this study, the bioinformatic tools have been used to construct a prognostic model with mitochondrial metabolism-related genes (MMRGs) to evaluate the survival, immune status, mutation profile, and drug sensitivity of PAAD patients.MethodUnivariate Cox regression and LASSO regression were used to screen the differentially expressed genes (DEGs), and multivariate Cox regression was used to develop the risk model. Kaplan–Meier estimator was employed to identify MMRGs signatures associated with overall survival (OS). ROC curves were utilized to evaluate the model's performance. Maftools, immunedeconv and CIBERSORT R packages were applied to analyze the gene mutation profiles and immune status. The corresponding sensitivity to pharmaceutical agents was assessed using oncoPredict R packages.ResultsA prognostic model with five MMRGs was developed, which defined the patients as high-risk showed lower survival rates. There was good consistency among individuals categorized as high-risk, showing elevated rates of genetic alterations, particularly in the TP53 and KRAS genes. Furthermore, these patients exhibited increased levels of immunosuppression, characterized by an increased presence of macrophages, neutrophils, Th2 cells, and regulatory T cells. Additionally, high-risk patients showed increased sensitivity to Sabutoclax and Venetoclax.ConclusionBy utilizing a gene signature associated with mitochondrial metabolism, a prognostic model has been established which could be a highly efficient method for predicting the outcomes of PAAD patients.

Risk factors for biliary strictures and leaks after living-donor liver transplantation: a systematic review and meta-analysis

BackgroundLiver transplantation is the only curative treatment of end-stage liver disease. Unfortunately, a significant number of patients on the organ waitlist die waiting for an organ. Living-donor liver transplantation (LDLT) is an approach that has been used to expand organ availability. Although LDLT has excellent outcomes, biliary complications remain a significant drawback. This meta-analysis aimed to precisely assess the predictors of biliary stricture and leak after LDLT. MethodsPubMed, Embase, and Web of Science databases were searched from inception to January 2024. Only studies that used a multivariate model to assess risk factors for post-LDLT biliary stricture or leak in adult participants were included. Studies reporting unadjusted risk factors were excluded. Pooled adjusted odds ratios (ORs) and pooled hazard ratios (HRs) with 95% CIs for risk factors reported in ≥2 studies were obtained within a random-effects model. ResultsOverall, 22 studies with 9442 patients who underwent LDLT were included. The post-LDLT biliary stricture rate was 22%, whereas the post-LDLT biliary leak rate was 14%. In addition, 13 unique risk factors were analyzed. Postoperative bile leak (OR, 4.10 [95% CI, 2.88–5.83]; HR, 3.88 [95% CI, 2.15–6.99]) was the most significant predictor of biliary stricture after LDLT. Other significant predictors of biliary stricture after LDLT were right lobe graft (OR, 2.56; 95% CI, 1.23–5.32), multiple ducts for anastomosis (OR, 1.62; 95% CI, 1.08–2.43), ductoplasty (OR, 2.07; 95% CI, 1.36–3.13), ABO incompatibility (OR, 1.45; 95% CI, 1.16–1.81), and acute cellular rejection (OR, 4.10; 95% CI, 2.88–5.83). Donor bile duct size (HR, 0.82; 95% CI, 0.74–0.91; P = .001, I2 = 0%) was found to be significantly associated with reduced risk of post-LDLT biliary stricture. Donor age, recipient age, recipient male sex, and duct-to-duct anastomosis were not associated with an increased risk of post-LDLT biliary strictures. Multiple ducts for anastomosis (OR, 1.86; 95% CI, 1.43–2.43) was a significant predictor of post-LDLT biliary leak. Recipient age, warm ischemia time, and duct-to-duct anastomosis were not associated with an increased risk of post-LDLT biliary leak. ConclusionIn this meta-analysis, 7 unique risk factors were shown to be predictive of post-LDLT biliary stricture, one of which was associated with both post-LDLT biliary stricture and leak. Donor bile duct size was found to be protective against post-LDLT biliary strictures. Identifying reliable predictors is crucial for recognizing high-risk patients. This approach can facilitate the implementation of preventive measures, surveillance protocols, and targeted interventions to reduce the incidence of biliary strictures after LDLT.

Analysis of Intravenous Ketamine Bolus in Pediatric Emergency Care

Considering the increasing use of intravenous ketamine in pediatric emergency care, particularly for sedation, analgesia, and management of severe conditions such as traumatic brain injury and suicidal ideation, there is a need to critically evaluate its efficacy and safety in these settings. This study aims to systematically review and analyze various studies that have investigated the use of intravenous ketamine bolus in pediatric emergency care, focusing on its clinical outcomes, safety profile, and overall effectiveness. To achieve this, a narrative literature review was conducted, examining studies published between 2014 and 2023. The review included randomized controlled trials, observational studies, and case reports sourced from reputable databases such as PubMed, Scopus, and Web of Science. The results of the review indicate that intravenous ketamine is effective in providing rapid sedation and analgesia, with a favorable safety profile when administered by trained healthcare professionals. Specifically, it was observed that ketamine significantly reduces pain intensity, lowers suicidal ideation, and effectively manages intracranial pressure in children with severe traumatic brain injury. However, the review also highlights the variability in recovery times and the incidence of mild to moderate side effects, such as dizziness, nausea, and drowsiness. In addition, the need for rescue doses was more frequent in intravenous administration compared to intramuscular routes, though intravenous administration offered quicker onset and shorter duration of action. It is concluded that while intravenous ketamine is a valuable tool in pediatric emergency care, its administration should be carefully monitored, particularly in high-risk patients, to mitigate potential adverse effects. Further research is needed to refine dosing strategies, explore long-term outcomes, and establish standardized protocols to maximize the therapeutic benefits of ketamine while minimizing risks.

MiR-124 in Neuroblastoma: Mechanistic Insights, Biomarker Potential, and Therapeutic Prospects

Abstract: Neuroblastoma, a malignancy predominantly affecting young children, originates from neural crest cells in the sympathetic nervous system. It primarily appears in the adrenal gland but can also affect nerve tissues in regions, such as the chest, neck, abdomen, and pelvis. Despite advancements in treatment, high-risk neuroblastoma patients often face poor prognoses, underscoring the need for ongoing research. This review paper examines the numerous factors responsible for neuroblastoma, emphasizing the importance of approaching the disorder with more strategic therapeutic methods. MicroRNAs, particularly miR-124, play critical roles in gene regulation and cancer pathogenesis. Abundant in the brain, miR-124 functions as a tumor suppressor by inhibiting cell growth, migration, and invasion and is often dysregulated in neuroblastoma. This study investigates the molecular functions of miR-124 in neuroblastoma, its potential as a biomarker, and its application in targeted therapy. MiR-124 regulates key pathways in neuroblastoma, including PI3K/AKT, TGF-β, and p53 signaling, impacting cell proliferation, apoptosis, and metastasis. The study also explores the promise of miR-124 as a biomarker for neuroblastoma through liquid biopsy, enabling non-invasive diagnosis and disease monitoring. Therapeutic strategies targeting miR-124 pathways show potential for overcoming chemotherapy resistance and improving treatment efficacy. The research underscores the significance of miR-124 in neuroblastoma, aiming to enhance early diagnosis, identify specific drug targets, and expand treatment options, ultimately improving patient outcomes.

DeepMonitoring: a deep learning-based monitoring system for assessing the quality of cornea images captured by smartphones.

Smartphone-based artificial intelligence (AI) diagnostic systems could assist high-risk patients to self-screen for corneal diseases (e.g., keratitis) instead of detecting them in traditional face-to-face medical practices, enabling the patients to proactively identify their own corneal diseases at an early stage. However, AI diagnostic systems have significantly diminished performance in low-quality images which are unavoidable in real-world environments (especially common in patient-recorded images) due to various factors, hindering the implementation of these systems in clinical practice. Here, we construct a deep learning-based image quality monitoring system (DeepMonitoring) not only to discern low-quality cornea images created by smartphones but also to identify the underlying factors contributing to the generation of such low-quality images, which can guide operators to acquire high-quality images in a timely manner. This system performs well across validation, internal, and external testing sets, with AUCs ranging from 0.984 to 0.999. DeepMonitoring holds the potential to filter out low-quality cornea images produced by smartphones, facilitating the application of smartphone-based AI diagnostic systems in real-world clinical settings, especially in the context of self-screening for corneal diseases.

A proposed clinical tool to identify high-risk patients for monogenic lupus: a pilot study.

To develop an easy-to-use and efficient clinical score to identify monogenic lupus based on clinical presentations and to stratify patients who may benefit from confirmatory molecular genetic testing. A comprehensive literature review identified 55 distinct items across 12 clinical and laboratory domains, narrowed down to the top ten by a panel of 12 expert paediatric rheumatologists with 80% consensus. The proposed score was tested in a pilot study on 10 patients with monogenic lupus and 30 control subjects with various autoimmune and autoinflammatory diseases. All patients, both with monogenic lupus and the control group, were then scored, and a receiver operating characteristic curve was employed to determine the threshold that distinguishes monogenic lupus from non-monogenic lupus. The clinical score comprised 10 items. Among all patients, the most frequent items were antinuclear antibody positivity and consanguinity, followed by early disease onset (<5 years), with no significant differences between monogenic lupus patients and the controls. However, the monogenic lupus patients exhibited significantly higher rates of family history of lupus, failure to thrive, cutaneous lesions, brain imaging changes, a low C1q level, and recurrent infections. Also, they achieved the highest scores compared to the controls. A score of more than three was found to be highly predictive for diagnosing monogenic lupus, with a sensitivity of 90% and a specificity of 90%. Our clinical score appears to be a valuable tool for the early identification of patients with monogenic lupus who may require further molecular genetic testing for confirmation.