Low-risk Patients Research Articles

Evolving role of staging CT scans during CT-angiography for DIEP flap reconstruction planning

BackgroundPre-operative planning with CTA in DIEP flap reconstruction is an essential preoperative tool. The aim of this study was to describe the management of the incidental findings following introduction and further modification of a combined CTA and CT-staging pre-operative protocol which include chest, abdomen, pelvis and musculoskeletal system. Material, methodA retrospective case series of 292 patients (Group1) with breast cancer who underwent DIEP flap between 2015 and 2019. This was followed by a re-assessment between 2019 and 2021 for 101 patients (Group 2) following modification of the staging-CT protocol for only those patients who received chemotherapy. Group 1 includes both of immediate and delayed reconstruction and, but the Group 2 includes only the high-risk cases of delayed reconstruction. Both groups had CT staging. Result30% of Group 1, most likely who had the delayed reconstruction, had findings which were recommended for further follow-up. This led to a change in staging of high-risk patients only at the end of 2019 to those who underwent chemotherapy who had delayed reconstruction.56.4% of Group 2 demonstrated incidental findings, 42.1% of them necessitated repeat scanning, 7% were referred to other specialties and 47.4% did not require further action There were no cases of occult metastatic breast cancer in either series; however, 1% were diagnosed with de novo primary cancers at non breast sites in the first series only. ConclusionThe screening of asymptomatic breast cancer patients as part of CTA scanning prior to autologous reconstruction is not universally practiced and not supported by NICE guidelines. This unit has changed practice to stop pre-operative staging for low-risk patients at the end of 2019, reserving it for the high-risk patient groups to reduce cost.

Diagnosis and Treatment of Membranous Nephropathy in Integrative Medicine

Membranous nephropathy (MN) is a common glomerular disease. The related pathological changes are primarily characterized by the deposition of immune complexes beneath the epithelial cells of the glomerular basement membrane, accompanied by diffuse thickening of the basement membrane. Its etiology and pathogenesis are not fully understood yet; however, they are associated with genetics, infections, tumors, drugs, heavy metals poisoning, environmental pollution, and the loss of immune tolerance. Over 10 target antigens, including the phospholipase A2 receptor (PLA2R) and thrombospondin type 1 domain containing 7A (THSD7A), associated with MN have been identified, each having different clinical implications. Clinical manifestations of MN patients mainly include proteinuria and nephrotic syndrome, with a propensity to form thrombi. Its diagnostic accuracy can be enhanced by combining clinical manifestations, serum antibody testing, and renal biopsy. Proteinuria, estimated glomerular filtration rate (eGFR), and PLA2R antibody levels are vital for the prognostic risk stratification of MN. Low-risk patients primarily undergo non-immunosuppressive treatment (angiotensin-converting enzyme inhibitor [ACEI]/angiotensin II receptor blocker [ARB], sodium-glucose cotransporter 2 inhibitor [SGLT2i], anticoagulants, and traditional Chinese medicine [TCM] treatments), while high-risk patients need to consider using steroids and immunosuppressants, such as cyclophosphamide (CTX), calcineurin inhibitors (CNIs), and anti-cluster of differentiation 20 (anti-CD20) monoclonal antibodies. TCM holds that MN is the imbalance of Fei (lung), Pi (spleen), and Shen (kidney) function, leading to the generation of Neixie such as Shi, Re, Du, and Yu. This disease is difficult to heal because of Shire and Yu. The treatment is based on the use of Jianpi Bushen, simultaneously emphasizing the use of drugs for Qingre Qushi Huoxue. Dialectical use of TCM can obviously improve the clinical response rate and alleviate symptoms such as edema and fatigue by increasing the serum albumin level more rapidly while introducing fewer adverse reactions. Combined with Western medicine, TCM can also reduce toxicity and increase efficiency. This article systematically reviews the etiology, podocyte antigens, clinical manifestations, diagnostic approaches, risk assessment, and integrative medicine therapeutic strategies for MN, aiming to deepen the understanding of MN and guide clinical practice.

The European Society of Cardiology quality indicators in atrial fibrillation in centers of excellence in Spain: the SEC-EXCELENTE FA registry

Introduction and objectivesBy 2022, 9 centers had been accredited by the Spanish Society of Cardiology for the atrial fibrillation (AF) process. Our objective was to evaluate the performance of these centers based on the quality indicators (QIs) proposed by the European Society of Cardiology (ESC) in 2020. MethodsAdults with AF who were attended in the cardiology departments of participating centers during the second week of May 2019 were included in a retrospective registry (n=797, age 72±11 years, 60% male). Key ESC QIs were assessed. ResultsCHA2DS2-VASc, HAS-BLED scores, and serum creatinine levels were documented in 24.9%, 6.1%, and 96.2% of patients, respectively. Anticoagulation was appropriately prescribed in 90.6% of high-risk patients according to the CHA2DS2-VASc score, but was inappropriately prescribed in 57.8% of low-risk patients. Among all patients, 84.1% received high-quality anticoagulation. Inappropriate antiarrhythmic drugs were prescribed in 7.2% of patients with permanent AF, 2.9% of those with structural heart disease, and 0.0% of those with end-stage kidney disease. Catheter ablation was offered to 70% of patients with symptomatic paroxysmal or persistent AF after the failure or intolerance of 1 antiarrhythmic drug. All modifiable risk factors were documented in 59.3% of patients. Rates of all-cause mortality, ischemic stroke or transient ischemic attack, and major bleeding were 8.1, 0.8, and 2.56 per 100 patients/y, respectively. QIs for anticoagulation and outcomes were similar between general cardiology and tertiary referral centers. ConclusionsAlthough accredited centers in Spain demonstrated good performance in many of the ESC QIs for AF, there remains room for improvement. These data could serve as a starting point for enhancing the quality of care in this population.

A management algorithm for idiopathic intracranial hypertension in skull base meningoencephaloceles.

In this study, the authors assessed an algorithm for the diagnosis and management of idiopathic intracranial hypertension (IIH) in patients who had undergone surgical repair of skull base meningoencephaloceles presenting with spontaneous cerebrospinal fluid (sCSF) leakage. The authors conducted an institutional retrospective review of patients surgically treated for skull base sCSF leaks between 2014 and 2021. Opening pressure (OP) measurements were taken intraoperatively. The algorithm recommended a ventriculoperitoneal shunt (VPS) for high-risk patients (OP ≥ 30 cm H2O), 4 weeks of acetazolamide plus a 2-week washout and repeat lumbar puncture (LP) at 6 weeks for intermediate-risk patients (OP = 20-29 cm H2O), and repeat LP at 4-6 weeks for low-risk patients (OP < 20 cm H2O). Demographics, radiographic characteristics, management adherence, and outcomes were analyzed. Eighty patients with sCSF leakage were identified. The mean age was 51.9 years, and the mean body mass index was 36.3 kg/m2. The median follow-up was 8.3 months (IQR 3.3-19.7 months). The overall VPS rate was 15.0%. Three patients (3.8%) experienced acute recurrent leakage, and 3 (3.8%) developed remote recurrent leaks (mean time of 48.1 months). For the 50 patients with both intra- and postoperative OPs, the mean OPs were not significantly different (23.3 vs 23.0 cm H2O, respectively, p = 0.82). The mean variability between the two measurements was an absolute difference of 6.6 cm H2O. While 13 patients (26.0%) moved to a higher-risk category based on postoperative OP, 18 patients (36.0%) moved to a lower-risk category. Utilizing an algorithm of direct meningoencephalocele repair and selective shunting, acute and remote CSF leak recurrence rates were each 3.8%, and the VPS rate was 15.0%. These data provide further insight into CSF dynamics in this population and argue against the theoretical concern that CSF pressure will increase postrepair. Significant intraindividual variability suggests multiple LPs may be necessary before committing to invasive IIH treatment. Further work is necessary to determine the optimal IIH management strategy.

The impact of cut-off values on the prevalence of short cervical length in pregnancy

BackgroundA prior study suggested that implementing a cut-off value of ≤30 mm for a short cervical length (CL) could potentially introduce selection bias and alter the distribution of CL measurements. As such, the objective of this study is to evaluate how CL distribution and incidence of short CL are affected when using different cut-off values for a short CL. Study designThis is a secondary analysis of the Quadruple P (QP) Screening study; a prospective cohort study that included low-risk patients with singleton pregnancies undergoing fetal anomaly scan at 18–22 weeks of gestation, including a CL measurement. Patients with a short cervix, defined as ≤35 mm, were subsequently counseled for the QP trial; a randomized controlled trial (RCT) comparing progesterone to cervical pessary for the prevention of preterm birth. If participation to the RCT was refused, patients with a CL ≤25 mm were advised to use progestogen. The primary objective of this current study was to assess the normal distribution of CL across the entire cohort and to assess the incidence of short CL when using the cut-off values of ≤35 and ≤25 mm. Normal distributions for CL were simulated based on mean and standard deviation(SD) of the original data. The Kolmogorov-Smirnov test was used to evaluate the distribution of the CL measurements. Moreover, to evaluate the motives behind ultrasound measurements around the cut-off value, sonographers were asked to fill out a qualitative questionnaire. ResultsThe total cohort included 19.171 eligible participants who underwent CL measurement, with a mean CL of 43.9 mm (±8.1 SD). The distribution of all CL observed measurements deviated significantly from the normal distribution (p < 0.001). A total of 1.852 (9.7%) patients had short CL ≤35 mm, which was significantly lower than expected when compared to the simulated normal distribution (n = 2.661, 13.9%; p < 0.001). The incidence of short CL ≤25 mm in our cohort statistically differed from the simulated normal distribution (238, 1.2% vs 177, 0.9%; p=0.003). When comparing our data to the simulated normal distribution, the difference in distributions is most pronounced when examining the difference between 35 and 36 mm. Results of the questionnaire reveal sonographers claimed not to be influenced by a cut-off value for study participation or progesterone treatment. ConclusionThis study demonstrates that using any cut-off value for a short CL influences the incidence and distribution of CL. When using a cut-off value of ≤35 mm for study inclusion, the incidence of measurements of a short CL is lower than the anticipated incidence compared to a normal distribution. However, when using a cut-off value of ≤25 mm for progesterone treatment, the frequency of CL measurements is higher than expected below this threshold compared to a normal distribution. This study highlights the risk of introducing selection bias, most likely unintentionally, when cut-off values for short CL are used, regardless of the specific value chosen. Therefore healthcare providers should measure the CL with caution if essential decisions depend on a specific cut-off value.

Aortic valve replacement vs. conservative treatment in asymptomatic severe aortic stenosis: long-term follow-up of the AVATAR trial.

The question of when and how to treat truly asymptomatic patients with severe aortic stenosis (AS) and normal left ventricular (LV) systolic function is still subject to debate and ongoing research. Here, the results of extended follow-up of the AVATAR trial are reported (NCT02436655, ClinicalTrials.gov). The AVATAR trial randomly assigned patients with severe, asymptomatic AS and LV ejection fraction ≥ 50% to undergo either early surgical aortic valve replacement (AVR) or conservative treatment with watchful waiting strategy. All patients had negative exercise stress testing. The primary hypothesis was that early AVR will reduce a primary composite endpoint comprising all-cause death, acute myocardial infarction, stroke, or unplanned hospitalization for heart failure (HF), as compared with conservative treatment strategy. A total of 157 low-risk patients (mean age 67 years, 57% men, mean Society of Thoracic Surgeons score 1.7%) were randomly allocated to either the early AVR group (n = 78) or the conservative treatment group (n = 79). In an intention-to-treat analysis, after a median follow-up of 63 months, the primary composite endpoint outcome event occurred in 18/78 patients (23.1%) in the early surgery group and in 37/79 patients (46.8%) in the conservative treatment group [hazard ratio (HR) early surgery vs. conservative treatment 0.42; 95% confidence interval (CI) 0.24-0.73, P = .002]. The Kaplan-Meier estimates for individual endpoints of all-cause death and HF hospitalization were significantly lower in the early surgery compared with the conservative group (HR 0.44; 95% CI 0.23-0.85, P = .012, for all-cause death and HR 0.21; 95% CI 0.06-0.73, P = .007, for HF hospitalizations). The extended follow-up of the AVATAR trial demonstrates better clinical outcomes with early surgical AVR in truly asymptomatic patients with severe AS and normal LV ejection fraction compared with patients treated with conservative management on watchful waiting.

Exploring the Influence of T Cell Marker Gene Expression on the Pathobiology and Clinical Prognostic Outcomes in Intestinal-Type Gastric Carcinoma.

Gastric cancer (GC) poses a significant global health challenge. This study is aimed at elucidating the role of the immune system, particularly T cells and their subtypes, in the pathogenesis and progression of intestinal-type gastric carcinoma (GC), and at evaluating the predictive utility of a T cell marker gene-based risk score for overall survival. We performed an extensive analysis using single-cell RNA sequencing data to map the diversity of immune cells and identify specific T cell marker genes within GC. Pseudotime trajectory analysis was employed to observe the expression patterns of tumor-related pathways and transcription factors (TFs) at various disease stages. We developed a risk score using data from The Cancer Genome Atlas (TCGA) as a training set and validated it with the GSE15459 dataset. Our analysis revealed distinct patterns of T cell marker gene expression associated with different stages of GC. The risk score, based on these markers, successfully stratified patients into high-risk and low-risk groups with significantly different overall survival prospects. High-risk patients exhibited poorer survival outcomes compared to low-risk patients (p < 0.05). Additionally, the risk score was capable of identifying patients across a spectrum from chronic atrophic gastritis to early GC. The findings enhance the understanding of the tumor immune microenvironment in GC and propose new immunotherapeutic targets. The T cell marker gene-based risk score offers a potential tool for gastroenterologists to tailor treatment plans more precisely according to the cancer's severity.

Developing a Podiatric Telemedicine Framework for Service Users and Providers in a Primary-Care Setting.

The use of telemedicine has garnered significant traction amidst the COVID-19 pandemic. The sudden adoption of certain practices in podiatry was not always supported by empirical evidence, resulting in the development of guidelines and metrics that lacked a foundation in rigorous research. A modified Delphi composed of three rounds was conducted with 16 stakeholders (service users, foot and ankle health-care providers, and policymakers) from a primary-care setting to develop a podiatric telemedicine framework for a primary-care setting. The first round consisted of focus group discussions, the second round consisted of a questionnaire composed of different statements that emerged from focus group discussions, and the final third round consisted of a questionnaire with statements from the second round that required further reiterations. Statements that achieved an 80% or higher level of agreement were accepted to form part of the podiatric telemedicine framework. Excellent consensus data was obtained to develop the podiatric telemedicine framework. Although podiatric telemedicine for low-risk patients in a primary-care setting is relatively new, stakeholders highlighted the importance of having podiatric telemedicine guidelines and setting service user and provider expectations clear on what podiatric telemedicine has to offer and its pitfalls. The podiatric telemedicine framework developed is recommended to all foot and ankle health-care professionals in a primary-care setting who wish to provide telemedicine consultations. Moreover, it is recommended that a pilot study be carried out to look into the feasibility of this framework being translated and implemented as a guideline related to foot and ankle telemedicine consultations.

Anoikis-related subtype and prognosis analyses based on bioinformatics, and an expression verification of ANGPTL4 based on experiments of lung adenocarcinoma.

Lung adenocarcinoma (LUAD) is one of the most common malignant tumors with high mortality. Anoikis resistance is an important mechanism of tumor cell proliferation and migration. Our research is devoted to exploring the role of anoikis in the diagnosis, classification, and prognosis of LUAD. We downloaded the expression profile, mutation, and clinical data of LUAD from The Cancer Genome Atlas (TCGA) database. The "ConsensusClusterPlus" package was then used for the cluster analysis, and least absolute shrinkage and selection operator (LASSO) and multivariate Cox regression analyses were used to establish the prognostic model. We verified the reliability of the model using a Gene Expression Omnibus (GEO) data set. A gene set variation analysis (GSVA) was conducted to investigate the functional enrichment differences in the different clusters and risk groups. The CIBERSORT algorithm and a single-sample gene set enrichment analysis (ssGSEA) were used to analyze immune cell infiltration. The tumor mutation burden (TMB) and Tumor Immune Dysfunction and Exclusion (TIDE) scores were used to evaluate the patients' sensitivity to immunotherapy. Immunohistochemical staining of tissue microarrays was used to verify the correlation between ANGPTL4 expression and the clinicopathological characteristics and prognosis of LUAD patients. First, we screened 135 differentially expressed anoikis-related genes (ARGs) and 23 prognosis-related ARGs from TCGA-LUAD data set. Next, 494 LUAD samples were allocated to cluster A and cluster B based on the 23 prognosis-related ARGs. The Kaplan-Meier (K-M) analysis showed the overall survival (OS) of cluster B was better than that of cluster A. The clinicopathological characteristics and functional enrichment analyses revealed significant differences between clusters A and B. The tumor microenvironment (TME) analysis showed that cluster B had more immune cell infiltration and a higher TME score than cluster A. Subsequently, a LASSO Cox regression model of LUAD was constructed with ten ARGs. The K-M analysis showed that the low-risk patients had longer OS than the high-risk patients. The receiver operating characteristic curve, nomogram, and GEO data set verification results showed that the model had high accuracy and reliability. The level of immune cell infiltration and TME score were higher in the low-risk group than the high-risk group. The high-risk group had stronger sensitivity to immune checkpoint block therapy and weaker sensitivity to chemotherapy drugs than the low-risk group. ANGPTL4 expression was correlated with stage, tumor differentiation, tumor size, lymph node metastasis, and OS. We discovered novel molecular subtypes and constructed a novel prognostic model of LUAD. Our findings provide important insights into subtype classification and the accurate survival prediction of LUAD. We also identified ANGPTL4 as a prognostic indicator of LUAD.

Identifying epithelial-mesenchymal transition-related genes as prognostic biomarkers and therapeutic targets of hepatocellular carcinoma by integrated analysis of single-cell and bulk-RNA sequencing data.

Hepatocellular carcinoma (HCC) remains one of the most lethal cancers globally. Patients with advanced HCC tend to have poor prognoses and shortened survival. Recently, data from bulk RNA sequencing have been employed to discover prognostic markers for various cancers. However, they fall short in precisely identifying core molecular and cellular activities within tumor cells. In our present study, we combined bulk-RNA sequencing (bulk RNA-seq) data with single-cell RNA sequencing (scRNA-seq) to develop a prognostic model for HCC. The goal of our research is to uncover new biomarkers and enhance the accuracy of HCC prognosis prediction. Integrating single-cell sequencing data with transcriptomics were used to identify epithelial-mesenchymal transition (EMT)-related genes (ERGs) implicated in HCC progression and their clinical significance was elucidated. Utilizing marker genes derived from core cells and ERGs, we constructed a prognostic model using univariate Cox analysis, exploring a multitude of algorithmic combinations, and further refining it through multivariate Cox analysis. Additionally, we conducted an in-depth investigation into the disparities in clinicopathological features, immune microenvironment composition, immune checkpoint expression, and chemotherapeutic drug sensitivity profiles between high- and low-risk patient cohorts. We developed a prognostic model predicated on the expression profiles of eight signature genes, namely HSP90AA1, CIRBP, CCR7, S100A9, ADAM17, ENG, PGF, and INPP4B, aiming at predicting overall survival (OS) outcomes. Notably, patients classified with high-risk scores exhibited a propensity towards diminished OS rates, heightened frequencies of stage III-IV disease, increased tumor mutational burden (TMB), augmented immune cell infiltration, and diminished responsiveness to immunotherapeutic interventions. This study presented a novel prognostic model for predicting the survival of HCC patients by integrating scRNA-seq and bulk RNA-seq data. The risk score emerges as a promising independent prognostic factor, showing a correlation with the immune microenvironment and clinicopathological features. It provided new clinical tools for predicting prognosis and aided future research into the pathogenesis of HCC.

Liquid-liquid phase separation-related features of PYGB/ACTR3/CCNA2/ITGB1/ATP8A1/RAP1GAP2 predict the prognosis of pancreatic cancer.

The growth and metastasis of pancreatic cancer (PC) has been found to be closely associated with liquid-liquid phase separation (LLPS). This study sought to identify LLPS-related biomarkers in PC to construct a robust prognostic model. Transcriptomic data and clinical information related to PC were retrieved from publicly accessible databases. The PC-related data set was subjected to differential expression, Mendelian randomization (MR), univariate Cox, and least absolute selection and shrinkage operator analyses to identify biomarkers. Using the biomarkers, we subsequently constructed a risk model, identified the independent prognostic factors of PC, established a nomogram, and conducted an immune analysis. The study identified four genes linked with an increased risk of PC; that is, PYGB, ACTR3, CCNA2, and ITGB1. Conversely, ATP8A1, and RAP1GAP2 were found to provide protection against PC. These findings contributed significantly to the development of a highly precise risk model in which risk, age, and pathology N stage were categorized as independent factors in predicting the prognosis of PC patients. Using these factors, a nomogram was established to predict survival outcomes accurately. An immune analysis revealed varying levels of eosinophils, gamma delta T cells, and other immune cells between the distinct risk groups. The high-risk patients exhibited increased potential for immune escape, while the low-risk patients showed a higher response to immunotherapy. Six genes were identified as having potential causal relationships with PC. These genes were integrated into a prognostic risk model, thereby serving as unique prognostic signatures. Our findings provide novel insights into predicting the prognosis of PC patients.

Women’s Perception of a Midwife-Led Clinic: A Qualitative Study

Background: While maternal and child health care is a crucial component of every healthcare system, the burden on medical staff in caring for low-risk pregnant patients could be significantly alleviated by recruiting and maintaining a substantial number of midwives. Objectives: This study aims to understand the perceptions of women recipients of antenatal services provided by midwife-led clinics (MLC). Method: The study utilised a phenomenological approach with semi-structured interviews to gather information from participants regarding their perceptions of the MLC. Results: Participants in the survey were women (n=13) who attended the MLC, the majority being over 30 years of age and graduates. The participants believed that the clinic was essential, and felt at ease with the midwife and the services. Most expressed satisfaction with the health education offered by the clinic on the subject of prenatal care, nutrition, exercise, and breastfeeding. Conclusion: The participants in this study preferred midwife-led clinics because they allowed for better communication, answered queries, and provided significant emotional support. The participants felt comfortable with the midwife, who created a forum for discussion and clarification of doubts.

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.

Diagnostic accuracy of a machine learning algorithm using point-of-care high-sensitivity cardiac troponin I for rapid rule-out of myocardial infarction: a retrospective study

Point-of-care (POC) high-sensitivity cardiac troponin (hs-cTn) assays have been shown to provide similar analytical precision despite substantially shorter turnaround times compared with laboratory-based hs-cTn assays. We applied the previously developed machine learning based personalised Artificial Intelligence in Suspected Myocardial Infarction Study (ARTEMIS) algorithm, which can predict the individual probability of myocardial infarction, with a single POC hs-cTn measurement, and compared its diagnostic performance with standard-of-care pathways for rapid rule-out of myocardial infarction. We retrospectively analysed pooled data from consecutive patients of two prospective observational cohorts in geographically distinct regions (the Safe Emergency Department Discharge Rate cohort from the USA and the Suspected Acute Myocardial Infarction in Emergency cohort from Australia) who presented to the emergency department with suspected myocardial infarction. Patients with ST-segment elevation myocardial infarction were excluded. Safety and efficacy of direct rule-out of myocardial infarction by the ARTEMIS algorithm (at a pre-specified probability threshold of <0·5%) were compared with the European Society of Cardiology (ESC)-recommended and the American College of Cardiology (ACC)-recommended 0 h pathways using a single POC high-sensitivity cardiac troponin I (hs-cTnI) measurement (Siemens Atellica VTLi as investigational assay). The primary diagnostic outcome was an adjudicated index diagnosis of type 1 or type 2 myocardial infarction according to the Fourth Universal Definition of Myocardial Infarction. The safety outcome was a composite of incident myocardial infarction and cardiovascular death (follow-up events) at 30 days. Additional analyses were performed for type I myocardial infarction only (secondary diagnostic outcome), and for each cohort separately. Subgroup analyses were performed for age (<65 years vs ≥65 years), sex, symptom onset (≤3 h vs >3 h), estimated glomerular filtration rate (<60 mL/min per 1·73 m2vs ≥60 mL/min per 1·73 m2), and absence or presence of arterial hypertension, diabetes, a history of coronary artery disease, myocardial infarction, or heart failure, smoking, and ischaemic electrocardiogram signs. Among 2560 patients (1075 [42%] women, median age 58 years [IQR 48·0-69·0]), prevalence of myocardial infarction was 6·5% (166/2560). The ARTEMIS-POC algorithm classified 899 patients (35·1%) as suitable for rapid rule-out with a negative predictive value of 99·96% (95% CI 99·64-99·96) and a sensitivity of 99·68% (97·21-99·70). For type I myocardial infarction only, negative predictive value and sensitivity were both 100%. Proportions of missed index myocardial infarction (0·05% [0·04-0·42]) and follow-up events at 30 days (0·07% [95% CI 0·06-0·59]) were low. While maintaining high safety, the ARTEMIS-POC algorithm identified more than twice as many patients as eligible for direct rule-out compared with guideline-recommended ESC 0 h (15·2%) and ACC 0 h (13·8%) pathways. Superior efficacy persisted across all clinically relevant subgroups. The patient-tailored, medical decision support ARTEMIS-POC algorithm applied with a single POC hs-cTnI measurement allows for very rapid, safe, and more efficient direct rule-out of myocardial infarction than guideline-recommended pathways. It has the potential to expedite the safe discharge of low-risk patients from the emergency department including early presenters with symptom onset less than 3 h at the time of admission and might open new opportunities for the triage of patients with suspected myocardial infarction even in ambulatory, preclinical, or geographically isolated care settings. The German Center for Cardiovascular Research (DZHK).

Artificial Intelligence Prediction of Cardiovascular Events Using Opportunistic Epicardial Adipose Tissue Assessments From Computed Tomography Calcium Score

BackgroundRecent studies have used basic epicardial adipose tissue (EAT) assessments (eg, volume and mean Hounsfield unit [HU]) to predict risk of atherosclerosis-related, major adverse cardiovascular events (MACEs). ObjectivesThe purpose of this study was to create novel, hand-crafted EAT features, “fat-omics,” to capture the pathophysiology of EAT and improve MACE prediction. MethodsWe studied a cohort of 400 patients with low-dose cardiac computed tomography calcium score examinations. We purposefully used a MACE-enriched cohort (56% event rate) for feature engineering purposes. We divided the cohort into training/testing sets (80%/20%). We segmented EAT using a previously validated, deep-learning method with optional manual correction. We extracted 148 initial EAT features (eg, morphologic, spatial, and HU), dubbed fat-omics, and used Cox elastic-net for feature reduction and prediction of MACE. Bootstrap validation gave CIs. ResultsTraditional EAT features gave marginal prediction (EAT-volume/EAT-mean-HU/BMI gave C-indices 0.53/0.55/0.57, respectively). Significant improvement was obtained with the 15-feature fat-omics model (C-index = 0.69, test set). High-risk features included the volume-of-voxels-having-elevated-HU-[-50,-30-HU] and HU-negative-skewness, both of which assess high HU values in EAT, a property implicated in fat inflammation. Other high-risk features include kurtosis-of-EAT-thickness, reflecting the heterogeneity of thicknesses, and EAT-volume-in-the-top-25%-of-the-heart, emphasizing adipose near the proximal coronary arteries. Kaplan-Meyer plots of Cox-identified, high- and low-risk patients were well separated with the median of the fat-omics risk, with the high-risk group having an HR 2.4 times that of the low-risk group (P < 0.001). ConclusionsPreliminary findings indicate an opportunity to use finely tuned, explainable assessments on EAT for improved cardiovascular risk prediction.

The Influence of Cough Reflex Testing on Patient Management.

Cough reflex testing (CRT) is an adjunct to the clinical swallowing evaluation (CSE), providing information on patients' risk of silent aspiration. CRT has been shown to influence diet recommendations, but in previous work, the many varied patient characteristics are not controlled. Therefore, the specific role of CRT results in these decisions remains unclear as this relationship has not been directly assessed. An online survey was sent to speech language therapists working in dysphagia. Two patient cases were presented that differed only by the presence of risk factors for the development of aspiration pneumonia. For each patient case, there were three assessment scenarios: CSE information only, CSE information with a "pass" CRT result, and CSE information with a "fail" CRT result. Clinicians outlined their patient management plans for each of the six scenarios. Ninety-seven data sets were used in the final analysis. A "fail" result was found to lead to the most restrictive patient management. Decisions made when provided with only CSE information were very similar to decisions made for a CSE with a "pass" result. Aspiration pneumonia risk factors were shown to influence decision making, with the low-risk patient more likely to be recommended a less restrictive diet. When information was available regarding silent aspiration risk, clinicians factored the results into their decision making. However, in the absence of a CRT result, airway sensation was assumed to be intact in the absence of information. This finding warrants further investigation given the impact this assumption may have on a patient's pulmonary health.

Identifying prognostic biomarkers in oral squamous cell carcinoma: an integrated single-cell and bulk RNA sequencing study on mitophagy-related genes

Oral squamous cell carcinoma (OSCC) has an extremely poor prognosis. Recent studies have suggested that mitophagy-related genes (MRGs) are closely correlated with the development and occurrence of cancer, but the role they play in oral cancer has not yet been explained.We conducted a comprehensive analysis of integrated single-cell and bulk RNA sequencing (RNA-seq) data retrieved from Gene Expression Omnibus (GEO) datasets and The Cancer Genome Atlas (TCGA) database. Multiple methods were combined to provide a comprehensive understanding of the genetic expression patterns and biology of OSCC, such as analysis of pseudotime series, CellChat cell communication, immune infiltration, Gene Ontology (GO), LASSO Cox regression, gene set variation analysis (GSVA), Kyoto Encyclopedia of Genes and Genomes (KEGG), gene set enrichment analysis (GSEA), Tumor Mutation Burden (TMB) and drug sensitivity assessments. The findings of this study demonstrated significantly greater activity of MRGs in NK cells than in other cells in OSCC. A reliable prognostic model was developed using 12 candidate genes strongly associated with mitochondrial autophagy. T stage, N stage and risk score were revealed as independent prognostic factors. Distinctively enriched pathways and immune cells were observed in different risk groups. Notably, low-risk patients were more responsive to chemotherapy. In addition, a nomogram model with excellent predictive ability was established by combining the risk scores and clinical features. The activity of MRGs suggest the potential for the development of new targeted therapies. The construction of a robust prognostic model also provides reference value for individualized prediction and clinical decision-making in patients with OSCC.

Coronary protective effect of the J-Valve during transcatheter aortic valve implantation for patients with aortic stenosis and low coronary artery openings

BackgroundIn recent years, transcatheter aortic valve implantation (TAVI) has become a widely used treatment for low-risk elderly patients. As an alternative to TAVI via the femoral artery, transapical TAVI (TA-TAVI) is a better surgical choice for patients with severe vascular diseases. The J-Valve assists doctors in completing valve implantation easily using its positioning locator device, which prevents the self-leaflet from approaching the sinus wall. This function acts as coronary artery protection to avoid coronary occlusion. However, the clinical prognosis of J-Valve implantation for patients with aortic valve stenosis and low coronary openings is unclear.MethodsA retrospective analysis was performed on 30 patients with aortic stenosis (AS) and coronary openings measuring ≤ 10 mm in height. All patients underwent TA-TAVI with J-Valve implantation. Patients were screened using preoperative computed tomography three-dimensional imaging of the aortic root, and the safety and efficacy of the procedure were evaluated. The collected indexes included patients’ general data, cardiac function, preoperative imaging parameters, intraoperative data and postoperative short-term prognosis.ResultsOf the 30 patients in the study successfully underwent TA-TAVI and J-Valve implantation. Two patients required temporary cardiopulmonary bypass assistance during the operation due to heart failure. The implant success rate was 100%, and there were no deaths within 30 days postoperatively. No patients experienced intraoperative or postoperative coronary artery occlusion. Postoperative echocardiography, physiological state and laboratory test results indicated that all patients recovered well. The electrocardiograms remained normal after TA-TAVI, and heart function improved within 30 days.ConclusionTransapical TAVI with J-Valve implantation is a safe and effective treatment option for patients with AS and a low coronary artery opening. Preoperative coronary artery evaluation and the locators of the J-Valve are crucial in preventing coronary artery occlusion. This treatment regimen provides beneficial outcomes and warrants further multi-centre clinical research in the future.

Laser ablation for preventing coronary obstruction and maintaining coronary access in redo-TAVR: A proof of concept.

Redo-transcatheter aortic valve replacement (TAVR) is a promising treatment for transcatheter aortic valve degeneration, becoming increasingly relevant with an aging population. In redo-TAVR, the leaflets of the initial (index) transcatheter aortic valve (TAV) are displaced vertically when the second TAV is implanted, creating a cylindrical cage that can impair coronary cannulation and flow. Preventing coronary obstruction and maintaining coronary access is essential, especially in young and low-risk patients undergoing TAVR. This study aimed to develop a new leaflet modification strategy using laser ablation to prevent coronary obstruction and facilitate coronary access after repeat TAVR. To evaluate the feasibility of the leaflet modification technique using laser ablation, the initial phase of this study involved applying a medical-grade ultraviolet laser for ablation through pericardial tissue. Following this intervention, computational fluid dynamics simulations were utilized to assess the efficacy of the resulting perforations in promoting coronary flow. These simulations played a crucial role in understanding the impact of the modifications on blood flow patterns, ensuring these changes would facilitate the restoration of coronary circulation. Laser ablation of pericardium leaflets was successful, demonstrating the feasibility of creating openings in the TAV leaflets. Flow simulation results show that ablation of index valve leaflets can effectively mitigate the flow obstruction caused by sinus sequestration in redo-TAVR, with the extent of restoration dependent on the number and location of the ablated openings. Laser ablation could be a viable method for leaflet modification in redo-TAVR, serving as a new tool in interventional procedures.

Derivation of a clinical prediction score for the diagnosis of clinically significant symptomatic carotid artery disease.

Emergent vascular imaging identifies a subset of patients requiring immediate specialized care (i.e. carotid stenosis > 50%, dissection or free-floating thrombus). However, most TIA patients do not have these findings, so it is inefficient to image all TIA patients in crowded emergency departments (ED). Our objectives were to derive and internally validate a clinical prediction score for clinically significant carotid arterydisease in TIA patients. This was a planned secondary analysis of a prospective cohort study from 14 Canadian EDs. Among 11555 consecutive adult ED patients with TIA/minor stroke symptoms over 12 years, 9882 had vascular imaging and were included in the analysis. Our main outcome was clinically significant carotid artery disease, defined as extracranial internal carotid stenosis ≥ 50%, dissection, or thrombus in the internal carotid artery, with contralateral symptoms. Of 9882 patients, 888 (9.0%) had clinically significant carotid artery disease. Logistic regression was used to derive a 13-variable reduced model. We simplified the model into a score (Symcard [Symptomatic carotid artery disease] Score), with suggested cut-points for high, medium, and low-risk stratification. A substantial portion (38%) of patients were classified as low-risk, 33.8% as medium risk, and 28.2% as high risk. At the low-risk cut-point, sensitivity was 92.9%, specificity 41.1%, and diagnostic yield 1.7%. This simple score can predict carotid artery disease in TIA patients using readily available information. It identifies low-risk patients who can defer vascular imaging to an outpatient or specialty clinic setting. Medium-risk patients may undergo imaging immediately or with slight delay, depending on local resources. High-risk patients should undergo urgent vascular imaging.