Risk Patients Research Articles

Digital innovation for cancer risk assessment allows large-scale service redevelopment of regional cancer genetics service delivery.

Family-history assessment can identify individuals above population-risk for cancer to enable targeted Screening, Prevention and Early Detection (SPED). The online patient-facing cancer Family History Questionnaire Service (cFHQS) is a digitalised, resource efficient tool for family history data capture to facilitate this. The capturing of digital data from cFHQS allows for data interrogation of patients referred to Clinical Genetics for the purposes of service improvement. Digital data from 4,044 cFHQS respondents over a three-year period was collected and interrogated with respect to the number and type of familial tumour diagnoses to enable service improvement and streamlining of referral pathways. 81% of colorectal and 71% of breast screening assessments were population- or moderate-risk. Most patients who completed cFHQS reported more than one diagnosis of cancer/tumour/polyps in their family. 2.5% of family history assessment patients had a second indication that required assessment that would have been missed if single tumour type assessment was undertaken. Implementation of an innovative, digital family history data collection pathway has allowed large scale interrogation of referral patterns and assessment outcomes to enable service development. The high volume of inappropriate referrals to Clinical Genetics for population and moderate risk patients highlighted the need for dedicated secondary care pathway provision for these patients. The use of cFHQS streamlined family history assessment allows for redistribution of resources to improve equity and access to genetic cancer risk assessment.

Re-Evaluating the Omission of Radiation Therapy in Low-Risk Patients with Early-Stage Breast Cancer

Traditionally, management of early-stage breast cancer has required adjuvant radiation therapy following breast conserving surgery, due to decreased local recurrence and breast cancer mortality. However, over the past decade, there has been an increasing emphasis on potential overtreatment of patients with early-stage breast cancer. This has given rise to questions of how to optimize de-intensification of treatment in this cohort of patients while maintaining clinical outcomes. A multitude of studies have focused on identification of a subset of patients with invasive breast cancer who were at low risk of local recurrence based on clinicopathologic features and therefore suitable for RT omission. These studies have failed to identify a subset that does not from RT with respect to local control. Several ongoing trials are evaluating alternative approaches to deintensification while focusing on tumor biology. With regards to ductal carcinoma in situ (DCIS), the role of RT has been questioned since breast conservation was utilized. Paralleling invasive disease studies, studies have sought to use clinicopathologic features to identify low risk patients suitable for RT omission but have failed to identify a subset that does not from RT with respect to local control. Use of new assays in patients with DCIS may represent the ideal approach for risk stratification and appropriate deintensification. At this time, when considering deintensification, individualizing treatment decisions with a focus on shared decision making is paramount.

Can Peripheral Perfusion Index Predict Disease Mortality in COVID-19 Patients in the Emergency Department

BackgroundCoronavirus disease 2019 (COVID-19) pneumonia remains a major public health concern. The prognostic efficacy of Peripheral Perfusion Index (PPI) has been researched in different pathologies such as trauma and sepsis. We hypothesized that PPI may serve as predictor of mortality in hospitalized patients with COVID-19 infection. This study aimed to describe the association between PPI at admission and COVID-19 mortality, a new mortality prediction tool. MethodsThis retrospective, observational study was conducted at a tertiary care center in Turkey. Adult patients diagnosed with COVID-19 infection were enrolled in this study between Februrary 15, 2022 to April 15, 2023. Patient demographic and clinical data including vital signs, laboratory parameters and PPI on admission were collected from an electronic database. PPI was measured using Philips G30E patient monitor system. The primary outcome was in-hospital mortality. ResultsIn total, 200 patients with COVID-19 infection were included and 42 (21%) in-hospital deaths were identified. For all parameters of study, age, oxygen saturation, respiratory rate, PPI, urea, creatinine, White Blood Cell (WBC), and High-sensitive cardiac Troponin T (hs-cTnT) values were significantly different between survivors vs non-survivors. hs-cTnT >21,25 pg/mL[HR:2.823 (95% CI:1.211– 6,583)], PPI <2,15 [HR:2,485 (95% CI:1.194–5.175)], Oxygen saturation <87% [HR:2,258 (95% CI:1.191–4.282)], and WBC >9680 x103/ml [HR:2.124 (95% CI:1.083–4.163)] were independent predictors of in-hospital mortality. ConclusionsThis study identified the factors affecting in-hospital mortality among COVID-19 patients. Importantly, besides many parameter, PPI at admission was significantly associated with COVID-19 mortality and could be a feasible marker in emergency department to identify high risk patients.

CD147 protein molecule expression and chromosomal instability in the pathogenesis and prognosis of thyroid cancer

Low-coverage whole genome sequencing was performed for tissue samples from thyroid patients who received surgery treatment from 2015 to 2021. The potential biological significance of CD147 protein in thyroid cancer was explored through correlation analysis of CD147 protein expression level and clinical features of thyroid cancer patients. Low coverage whole genome sequencing was performed on the extracted DNA samples. The copy number analysis software was used to analyze the sequencing data, calculate the copy number of CD147 gene, further verify the expression of CD147 gene, and analyze its association with clinical features. The relationship between CIN and high risk was evaluated in the internal cohort. The association of CIN with the disease-free survival was validated in the cohort from The Cancer Genome Atlas Program. Thyroglobulin plays a key role in regulating thyroid function and maintaining normal metabolic rate. By sequencing tissue samples from this study, we can gain a deeper understanding of the association between cin and thyroid disease. The percentage of high risk patients in the multiple CIN group (77.8 %) was significantly higher than that in the 22q negative group (31.3 %), BRAF V600E group (22.2 %) and all negative group (25.0 %; p = 0.043).

Laterality of Radiation Therapy in Breast Cancer is Not Associated with Increased Risk for Coronary Artery Disease in the Contemporary Era

BackgroundExternal beam radiation therapy (EBRT) is a critical component of breast cancer (BC) therapy. Given the improvement in technology in the contemporary era, we hypothesize there is no difference the development of or worsening of existing coronary artery disease (CAD) in patients with BC receiving left vs right sided radiation. MethodsFor the meta-analysis portion of our study, we searched PubMed, Web of Science, and Scopus and included studies from January 1999 to September 2022. CAD was identified using a homogenous metric across multiple studies included. We computed the risk ratio (RR) for included studies using a random effects model. For the institutional cohort portion of our study, we selected high cardiovascular risk patients diagnosed with BC between 2010-2022 if they met our inclusion criteria. We performed a Cox proportional hazards model with stepwise adjustment. ResultsA pooled random effects model with 9 studies showed that patients with left-sided BC receiving EBRT had a 10% increased risk of CAD when compared to patients with right-sided BC receiving EBRT (RR: 1.10, 95% CI: 1.02 - 1.18, p = 0.01). However, subgroup analysis of 6 studies that included patients diagnosed after 1980 did not show a significant difference in CAD based on BC laterality (RR: 1.07, 95% CI: 0.95 – 1.20, p = 0.27). For the institutional cohort portion of the study, we found that patients with left-sided BC who received EBRT did not have a significantly higher risk for CAD when compared to their right-sided counterparts (HR = 0.73, 95% CI: 0.34 - 1.54, p = 0.402). ConclusionOur study suggests a historical trend of increased CAD in BC patients receiving left-sided EBRT. Data from patients diagnosed after 2010 in our institutional cohort did not show a significant difference, emphasizing that modern EBRT regimens are safe, and laterality of BC does not affect CAD outcomes in the short term after a breast cancer diagnosis.

The current role of pentafecta in the reporting of radical cystectomy outcomes: a scoping review.

Pentafecta has recently been validated for reporting radical cystectomy (RC) outcomes in open, laparoscopic and robotic series. We aim in this review to explore the current role of pentafecta in the reporting of RC outcomes. A comprehensive literature search was performed in the PubMed database to identify relevant articles. The pentafecta achievement (PA) was defined originally as negative soft tissue surgical margin (NSTSM), lymph node (LN) dissection (LND) with removal of ≥16 LNs, absence of 90-days grade ≥3 Clavien-Dindo (CD) complications, a time interval of less than 3 months between the last transurethral resection of bladder tumor (TURBT) with evidence of muscle invasive bladder cancer (MIBC) and RC, and absence of local pelvic recurrence within 1 year. The definition was later modified and the last two criteria were replaced by absence of urinary diversion (UD) related complications and any clinical recurrence at one year. Twelve studies with 4,946 patients were enrolled in the present review. All the studies were retrospective except one recently published randomized study comparing open and robotic-assisted RC. Pentafecta was totally achieved in 34% and main causes of missing pentafecta were the number of resected LNs and 90-days major complications. Type of UD, increasing age, advanced tumor stage, and decreasing surgical experience were the factors most commonly associated with a lower likelihood of PA. A positive correlation was seen between PA and long-term oncological outcome and quality of life. The main limitations in the present studies are their retrospective nature, relatively small sample size, and short median follow-up, most of which was less than 3 years. The new pentafecta definition provides a comprehensive tool for reporting RC outcomes by including measures of postoperative morbidity, functional outcomes and local cancer control. Pentafecta include standards that could be useful for improving surgical quality, surgical education and comparing different techniques. However, pentafecta is not yet suitable for perioperative risk stratification and patient counseling.

Primary Prevention of Coronary Heart Disease: Issues of Concern

In the Russian Federation, cardiovascular diseases are one of the leading causes of both morbidity and mortality and high economic costs of healthcare. Early identification of risk factors for cardiovascular diseases and their primary prevention underlie the ongoing process to reduce these indicators. The purpose of this work was to conduct a clinical and epidemiological study to analyze the prevalence of risk factors for cardiovascular diseases in young and middle-aged people living in the Oryol region. Materials and methods: The prospective study included 353 young and middle-aged patients with acute forms of coronary artery disease (unstable angina and myocardial infarction) and 112 apparently healthy individuals. All respondents were assessed for cardiovascular risk factors and patient adherence to treatment, for a total of 21 parameters. Results: according to the study, it was found that among young and middle-aged patients living in the Oryol region, IHD develops against the background of traditional risk factors for cardiovascular diseases, the prevailing ones being arterial hypertension (88.6 %), sedentary lifestyle (68 %), poor nutrition (53.0 %) and alcohol consumption (52 %), their gender differences were established. Conclusion. The analysis of the frequency of occurrence of cardiovascular risk factors showed their widespread prevalence among the population, low awareness of the population and insufficient adherence of patients to treatment.

Early Feasibility Study with the SATURN Transapical Mitral Valve Replacement Device

PurposeTo report the outcomes of the early feasibility study of transapical transcatheter mitral valve replacement (TMVR) with the SATURN System (InnovHeart, Milano, Italy) to treat patients with severe functional mitral regurgitation. DescriptionFive high surgical risk patients underwent transapical transcatheter mitral valve replacement with the SATURN System at a single center. One-year follow-up is complete for all patients. EvaluationThe valve was implanted successfully in all patients without any major adverse events. All patients were alive at the last follow-up. Kansas City Cardiomyopathy Questionnaire improved from a median of 63.5 (interquartile range, 19.6) at baseline to 99.0 (interquartile range, 21.6) at 1 year. Echocardiographic follow-up demonstrates stable valve function, no transvalvular or paravalvular mitral regurgitation, and absence of left ventricular outflow tract obstruction. ConclusionsAt 1 year after transapical SATURN transcatheter mitral valve replacement, all patients are alive with quality of life improvement and favorable device hemodynamics. These initial results are promising and larger scale studies with continued follow-up are required to further elucidate the efficacy and safety of this novel technology.

Salvage High-Intensity Focused Ultrasound for Prostate Cancer after Radiation Failure: A Narrative Review.

For patients diagnosed with localized prostate cancer, there are multiple treatment options available. The traditional treatment modalities include radical prostatectomy and radiotherapy. Nevertheless, focal therapy, including high-intensity focused ultrasound (HIFU) and cryotherapy, has emerged as a less-invasive method in this setting. Some patients undergoing primary radiation therapy experience recurrence, but there is currently no consensus on the optimal approach for salvage treatment in such cases. The lack of robust data and randomized controlled trials comparing different whole-gland and focal salvage therapies presents a challenge in determining the ideal treatment strategy. This narrative review examines the prospective and retrospective data available on salvage HIFU following radiation therapy. Based on the literature, salvage HIFU for radio-recurrent prostate cancer has promising oncological outcomes, with an overall 5-year survival rate of around 85%, as well as incontinence rates of about 30% based on the patient's risk group, follow-up times, definitions used, and other aspects of the study. Salvage HIFU for prostate cancer proves to be an effective treatment modality for select patients with biochemical recurrence following radiotherapy.

Leveraging machine learning to develop a postoperative predictive model for postoperative urinary retention following lumbar spine surgery.

Postoperative urinary retention (POUR) is the inability to urinate after a surgical procedure despite having a full bladder. It is a common complication following lumbar spine surgery which has been extensively linked to increased patient morbidity and hospital costs. This study hopes to development and validate a predictive model for POUR following lumbar spine surgery using patient demographics, surgical and anesthesia variables. This is a retrospective observational cohort study of 903 patients who underwent lumbar spine surgery over the period of June 2017 to June 2019 in a tertiary academic medical center. Four hundred and nineteen variables were collected including patient demographics, ICD-10 codes, and intraoperative factors. Least absolute shrinkage and selection operation (LASSO) regression and logistic regression models were compared. A decision tree model was fitted to the optimal model to classify each patient's risk of developing POUR as high, intermediate, or low risk. Predictive performance of POUR was assessed by area under the receiver operating characteristic curve (AUC-ROC). 903 patients were included with average age 60 ± 15 years, body mass index of 30.5 ± 6.4 kg/m2, 476 (53%) male, 785 (87%) white, 446 (49%) involving fusions, with average 2.1 ± 2.0 levels. The incidence of POUR was 235 (26%) with 63 (7%) requiring indwelling catheter placement. A decision tree was constructed with an accuracy of 87.8%. We present a highly accurate and easy to implement decision tree model which predicts POUR following lumbar spine surgery using preoperative and intraoperative variables.

Feasibility of anticoagulation on demand after percutaneous coronary intervention in high-bleeding risk patients with paroxysmal atrial fibrillation The INTERMITTENT Registry

Abstract Aims This study evaluated the feasibility of the intermittent use of direct oral anticoagulants (DOACs) guided by continuous rhythm monitoring via a clinically validated wearable smart device in high-bleeding risk (HBR) patients with symptomatic paroxysmal atrial fibrillation (AF) otherwise subjected to chronic anticoagulation after percutaneous coronary intervention (PCI). Methods and results The INTERMITTENT registry was a 3-year prospective observational study at 8 Italian centers. Inclusion criteria were elective or urgent PCI, Academic Research Consortium HBR criteria, history of symptomatic 12-lead ECG detected paroxysmal AF episodes, indication to DOACs, and use of a wearable smart device (Apple WatchTM). Thirty days after PCI, patients free of AF episodes discontinued DOAC. However, if an AF episode lasting&amp;gt;6 minutes or a total AF burden&amp;gt;6 hours over 24 hours was detected, DOAC was initiated for 30 consecutive days, and withdrawn afterwards if no further AF episodes occurred. At the discretion of the referring physician, intermittent anticoagulation was offered to 89 patients, whereas continuous treatment with DOACs was prescribed to 151 patients. During a follow-up of 298+87 days, the average duration of oral anticoagulation was significantly shorter in the intermittent anticoagulation group (176+43 days, p=0.0001), representing a 40% reduction in anticoagulation time compared to the continuous group. Ischemic and bleeding end-points were not significantly different between the two groups. Propensity score-matching resulted in a total of 69 matched patients with intermittent versus continuous anticoagulation, respectively. During a follow-up of 291+63 days, there was a significant 46% reduction in anticoagulation time in the intermittent compared to the continuous group (p=0.0001). Conclusion In high-bleeding risk patients with a history of paroxysmal AF episodes who underwent PCI, intermittent anticoagulation guided by continuous rhythm monitoring with a wearable device was feasible and decreased significantly the duration of anticoagulation.

Detection of Cardiotoxicity Using Right Ventricular Free Wall Longitudinal Strain in Low Cardiovascular Risk Breast Cancer Patients Receiving Low-Dose Anthracycline Treatment.

Objective Breast cancer patients who receive chemotherapy may develop cancer therapy-related cardiovascular toxicity, particularly if they have pre-existing cardiovascular risk factors. Notably, right ventricle dysfunction may manifest before the left ventricle. Our study aims to compare conventional echocardiography with global longitudinal strain (GLS) in low cardiovascular risk patients on low-dose anthracycline, focusing on early cardiotoxicity detection. Additionally, we explore the predictive role of right ventricular free wall longitudinal strain (RVFWLS) in cardiotoxicity. Methods In a recent study, 28 women with low cardiovascular risk who underwent low-dose anthracycline chemotherapy for breast cancer were assessed for cardiac function using two-dimensional echocardiography and speckle-tracking echocardiography. The measurements included left ventricular ejection fraction (LVEF), right ventricular systolic function (RVS'), tricuspid annular plane systolic excursion (TAPSE), left ventricular global longitudinal strain (LVGLS), and RVFWLS. All patients had normal LVEF at the beginning of the study. Cardiotoxicity was defined as a new decrease in LVEF by 10% or below 53% and/or changes in LVGLS/RVFWLS by 15%. Results In our study, no significant changes were observed in the LVEF following chemotherapy treatment. The LVEF values remained stable, changing slightly from 63 ± 3.7 to 65.0 ± 3.4, with a t-test value of 1.790 and a p-value of 0.079. Similarly, the analysis found no significant changes in RVS' and TAPSE values following chemotherapy treatment. However, significant changes were observed in strain measurements. LVGLS decreased from -21.2 ± 2.1 to -18.6 ± 2.6 (t-test = -4.116; df = 54, p=0.001), and RVFWLS decreased from -25.2 ± 2.9 to -21.4 ± 4.4 (t-test = -3.82; df = 54, p=0.001). Notably, 35% of participants showed changes in RVFWLS greater than 15%, whereas LVGLS changed by less than 15%. This indicates that RVFWLS is more sensitive to the treatment compared to LVGLS. Conclusions The study results indicate that during the initial phases of chemotherapy treatment in low cardiovascular risk patients, early changes in strain measures reveal subclinical cardiotoxicity. This suggests that GLS measurements are more effective at detecting early signs of myocardial damage and potential deterioration in cardiac function than traditional echocardiographic parameters. Additionally, it is noteworthy that RVFWLS exhibits greater sensitivity to these changes, regardless of the chemotherapy dosage and regimen.

Syndecan-1 as a prognostic biomarker in COVID-19 patients: a retrospective study of a Japanese cohort

BackgroundThe coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has had a profound global impact, with millions of confirmed cases and deaths worldwide. While most cases are mild, a subset progresses to severe respiratory complications and death, with factors such as thromboembolism, age, and underlying health conditions increasing the risk. Vascular endothelial damage has been implicated in severe outcomes, but specific biomarkers remain elusive. This study investigated syndecan-1 (SDC-1), a marker of endothelial damage, as a potential prognostic factor for COVID-19, focusing on the Japanese population, which is known for its aging demographics and high prevalence of comorbidities.MethodsA multicenter retrospective study of COVID-19 patients in Fukushima Prefecture in Japan who were admitted between February 2020 and August 2021 was conducted. SDC-1 levels were measured along with other clinical and laboratory parameters. Outcomes including thrombosis, 28-day survival, and disease severity were assessed, and disease severity was categorized according to established guidelines.ResultsSDC-1 levels were correlated with disease severity. Patients who died from COVID-19 had greater SDC-1 levels than survivors, and the area under the receiver operating characteristic curve (AUC) analysis suggested the potential of the SDC-1 level as a predictor of mortality (AUC 0.714). K‒M analysis also revealed a significant difference in survival based on an SDC-1 cutoff of 10.65 ng/mL.DiscussionThis study suggested that SDC-1 may serve as a valuable biomarker for assessing COVID-19 severity and predicting mortality within 28 days of hospitalization, particularly in the Japanese population. However, further investigations are required to assess longitudinal changes in SDC-1 levels, validate its predictive value for long-term survival, and consider its applicability to new viral variants.ConclusionsSDC-1 is emerging as a potential biomarker for assessing the severity and life expectancy of COVID-19 in the Japanese population, offering promise for improved risk stratification and patient management in the ongoing fight against the virus.

Predicting perioperative myocardial injury/infarction after noncardiac surgery in patients under surgical and medical co-management: a prospective cohort study

BackgroundPerioperative myocardial injury/infarction (PMI) following noncardiac surgery is a frequent cardiac complication. This study aims to evaluate PMI risk and explore preoperative assessment tools of PMI in patients at increased cardiovascular (CV) risk who underwent noncardiac surgery under the surgical and medical co-management (SMC) model.MethodsA prospective cohort study that included consecutive patients at increased CV risk who underwent intermediate- or high-risk noncardiac surgery at the Second Medical Center, Chinese PLA General Hospital, between January 2017 and December 2022. All patients were treated with perioperative management by the SMC team. The SMC model was initiated when surgical intervention was indicated and throughout the entire perioperative period. The incidence, risk factors, and impact of PMI on 30-day mortality were analyzed. The ability of the Revised Cardiac Risk Index (RCRI), frailty, and their combination to predict PMI was evaluated.Results613 eligible patients (mean [standard deviation, SD] age 73.3[10.9] years, 94.6% male) were recruited consecutively. Under SMC, PMI occurred in 24/613 patients (3.9%). Patients with PMI had a higher rate of 30-day mortality than patients without PMI (29.2% vs. 0.7%, p = 0.00). The FRAIL Scale for frailty was independently associated with an increased risk for PMI (odds ratio = 5.91; 95% confidence interval [CI], 2.34–14.93; p = 0.00). The RCRI demonstrated adequate discriminatory capacity for predicting PMI (area under the curve [AUC], 0.78; 95% CI, 0.67–0.88). Combining frailty with the RCRI further increased the accuracy of predicting PMI (AUC, 0.87; 95% CI, 0.81–0.93).ConclusionsThe incidence of PMI was relatively low in high CV risk patients undergoing intermediate- or high-risk noncardiac surgery under SMC. The RCRI adequately predicted PMI. Combining frailty with the RCRI further increased the accuracy of PMI predictions, achieving excellent discriminatory capacity. These findings may aid personalized evaluation and management of high-risk patients who undergo intermediate- or high-risk noncardiac surgery.

COVID-19 impact on thrombotic complications in cancer patients

Aim: to study the features of thrombotic complications in cancer patients during COVID-19 infection, and identify the most significant diagnostic and prognostic criteria.Materials and Methods. Within the framework of cohort non-randomized study, there were analyzed the course of coronavirus infection in 72 hospitalized patients with uterine cancer (n = 22), cervical cancer (n = 19), ovarian cancer (n = 24) as well as vaginal and vulvar cancer (n = 7). All patients hospitalized for COVID-19 were examined and treated in accordance with the Interim guidelines “Prevention, diagnosis and treatment of novel coronavirus infection (COVID-19)” effective at the time of therapy. Additionally, on days 3–7 after hospitalization, a blood test was performed once to determine the level of metalloproteinase ADAMTS-13 (a disintegrin and metalloproteinase with thrombospondin type 1 motif, member 13), ADAMTS-13 activity, ADAMTS-13 inhibitor and von Willebrand factor (vWF) level.Results. It was shown that the average age of the patients was 56.96 ± 7.55 years, the length of hospitalization ranged from 7 to 19 (13.0 ± 3.79) days. The disease severity was assessed by the degree of lung tissue damage based on computed tomography (CT), respiratory failure and development of systemic inflammatory response syndrome (SIRS). During hospitalization, CT-2 was detected in 46 (63.9 %) patients, CT-3 – in 26 (36.1 %) patients; 37 (51.4 %) patients were transferred to the intensive care unit (ICU). Clinically significant deep vein thrombosis (DVT) was diagnosed in 9 (12.5 %) patients, and pulmonary embolism (PE) – in 4 (5.6 %) patients. Of these, 6 cases of DVT and 3 cases of PE were fatal. A total of 14 (19.44 %) patients deceased due to developing acute cardiopulmonary failure. A vWF/ADAMTS-13 ratio greater than 2.1 was found in all ICU patients. Despite anticoagulant therapy, patients with DVT and PE had this ratio higher than 3.3 (4.00 ± 0.48), whereas in all 14 deceased patients it exceeded 2.98.Conclusion. Venous thromboembolism, including PE and DVT, has been identified as а serious complication of COVID-19. An opportunity to predict them early is of special importance because they may lead to serious complications such as disseminated intravascular coagulation, SIRS, cardiopulmonary failure, and death. In patients suffering from cancer infected with COVID-19, not only a decline in ADAMTS-13 activity and level was detected, but also a parallel increase in vWF level. A vWF/ADAMTS-13 ratio may be an early indicator of COVID-19 severity in such patients: a vWF/ADAMTS-13 ratio exceeding 2.1 was common for all ICU patients. Hence, it evidences about a potential for using this parameter to early identify such risk patients who may require more intensive care and medical intervention.

MDB-70. SYSTEMATIC TRANSCRIPTOMIC ANALYSIS OF CHILDHOOD MEDULLOBLASTOMA IDENTIFIES M6A-LNCRNA SIGNATURES ASSOCIATED WITH PROGNOSIS, MOLECULAR SUBTYPE, AND IMMUNE CELL INFILTRATION

Abstract BACKGROUND Medulloblastoma (MB) is the predominant pediatric brain tumor, subdivided into four molecular subgroups, with group 3 and group 4 tumors posing significant clinical challenges due to poor prognosis and classification. This study investigates the roles of N6-methyladenosine (m6A) and long non-coding RNAs (lncRNAs) in MB, aiming to develop diagnostic and prognostic tools. METHODS We analyzed transcriptome from 1236 samples to identify m6A-associated lncRNA signature (M6LSig). A multivariate-cox analysis identified a gene signature significantly associated with overall survival (OS) of patients. Risk score was calculated based on the sum of weighted gene expression of these genes. Nomograms were calculated for predicting OS and PFS probability. We did feature selection with Boruta to identify minimum gene signature for subgroup classification. We performed correlation analysis of gene signature and risk score with immune-cell abundance. We depleted METTL3 and METTL14 in G3-MB cell-line (D425) to measure impact on cell proliferation and dysregulation of M6LSig genes as a result of loss of m6A. RESULTS Nomogram was constructed using risk score derived from 24 M6LSig significantly associated with OS and PFS of the patients. A 171 gene signature was identified that can accurately classify samples into one of four major subgroups of MB with more than 90% accuracy including between Grp3/Grp4 samples. M6LSig genes and risk score showed significant correlation with immune cell type abundance in MB tumors. Expression of CD155 and 4-1BB was significantly different between high and low risk samples. m6A writer genes knockdown in D425 cells resulted in decreased cell proliferation and upregulation of many M6LSig genes. CONCLUSION M6LSig based risk can accurately predict OS and PFS and 171 genes signature can classify patients into subgroups with more than 90% accuracy. Risk score can also be used for determining high risk versus low-risk patient and design tailor made immune-therapy for better survival.

A comparative study between curb-65 and psi/port score as predictors for ICU admission and mortality in community acquired pneumonia patients presenting to a tertiary care hospital

Despite recent advances in clinical medicine, mortality due to CAP has remained relatively the same. Therefore, early recognition for ICU admission plays a pivotal role in management of CAP. PSI/PORT (Pneumonia Severity Index/ Pneumonia Patient Outcome Research Team) score and CURB-65 (Confusion, Uremia, Respiratory rate, BP, Age &amp;#62; 65 years) are the two severity assessment scores that have extensively been used by the clinicians to distinguish between high risk and low risk patients. This study aims at comparing the predictive value of these two scores for ICU admission and mortality. The information required for calculating CURB-65 and PSI was extracted with careful history taking, patient assessment and necessary investigations. Patients with &amp;#62;18 years of age, diagnosed clinically and radiologically with CAP were included in the study.CURB-65 and PSI scores were determined in a total of 131 patients on admission. Based on careful clinical assessment and judgment of treating physician 60 patients were admitted in ICU whereas 71 patients were admitted in medical ward. Out of 60 patients admitted in ICU 23 died. The ability to predict ICU admission was almost similar for PSI/PORT score (AUC 0.9605; 95% CI 0.9277-0.9933) and CURB-65 (AUC 0.9694; 95% CI 0.9368-1.9714). The ability to predict mortality was almost similar for PSI/PORT score (AUC 0.9196; 95% CI 0.8670-0.9722) and CURB-65 (AUC 0.9214 95% CI 0.8696-0.9732). CURB-65 score was found almost similar in predicting ICU admission amongst patients coming with CAP to our hospital when compared to PSI/PORT score and when predicting mortality in patients with community-acquired pneumonia, CURB-65 and PSI/PORT score appear to have comparable specificity and sensitivity. Considering the simplicity, CURB-65 score could be preferred over PSI/PORT score. However, larger studies are required to know the exact Indian scenario. Despite of recent advances in the field of medical science the mortality due to CAP has remained relatively the same. Therefore, early diagnosis and admission to ICU with standard treatment play a pivot role in management of patients with CAP. Two scoring system, PSI/PORT score and CURB-65 score, are widely being used to differentiate between low risk and high risk patients. We undertook this study for comparing the predictive value of these two scores for ICU admission and mortality.

Classification of the Stages of Nonalcoholic Steatohepatitis via Federated General Visual Representation Learning

ABSTRACTThe excess buildup of fat within a patient's liver, even in the absence of any previous alcohol consumption, defines nonalcoholic fatty liver disease (NAFLD). Accurate classification of NAFLD subtypes, especially nonalcoholic steatohepatitis (NASH), through histology biopsies is vital for risk stratification and patient management, including liver transplantation decisions. Therapeutic options targeting liver molecular pathways are being explored, as approved therapies for NASH/NAFLD are currently lacking. Deep learning‐driven pathological diagnosis holds promise for precise assessments, and the application of the federated learning version of the Big Transfer (BiT) model in this study represents a significant advancement in NAFLD/NASH classification and staging using histopathological imaging data. The AUC performance results of federated learning settings of “mainclass” and “multiclass” scenarios are obtained respectively as 0.9299 and 0.9582. The AUC results of each “subclass” are achieved as 0.9376, 0.9435, 0.9867, and 0.9618 respectively, for ballooning, inflammation, steatosis, and fibrosis. The effectiveness of the federated learning configurations in the scenarios categorized as “main‐class” and “multi‐class” is reflected in their respective accuracy (ACC) performance outcomes, which are recorded as 0.7650 and 0.6653. Furthermore, the ACC achievements for each specific “sub‐class” namely, ballooning, inflammation, steatosis, and fibrosis are 0.9016, 0.8568, 0.9203, and 0.8815, respectively.

Three-dimensional cardiac magnetic resonance allows the identification of slow-conducting anatomical isthmuses in tetralogy of Fallot.

Patients with repaired tetralogy of Fallot remain at risk of life-threatening ventricular tachycardia related to slow-conducting anatomical isthmuses (SCAIs). Preventive ablation of SCAI identified by invasive electroanatomical mapping is increasingly performed. This study aimed to non-invasively identify SCAI using 3D late gadolinium enhancement cardiac magnetic resonance (3D-LGE-CMR). Consecutive tetralogy of Fallot patients who underwent right ventricular electroanatomical mapping (RV-EAM) and 3D-LGE-CMR were included. High signal intensity threshold for abnormal myocardium was determined based on direct comparison of bipolar voltages and signal intensity by co-registration of RV-EAM with 3D-LGE-CMR. The diagnostic performance of 3D-LGE-CMR to non-invasively identify SCAI was determined, validated in a second cohort, and compared with the discriminative ability of proposed risk scores. The derivation cohort consisted of 48 (34 ± 16 years) and the validation cohort of 53 patients (36 ± 18 years). In the derivation cohort, 78 of 107 anatomical isthmuses (AIs) identified by EAM were normal-conducting AI, 22 were SCAI, and 7 blocked AI. High signal intensity threshold was 42% of the maximal signal intensity. The sensitivity and specificity of 3D-LGE-CMR for identifying SCAI or blocked AI were 100% and 90%, respectively. In the validation cohort, 85 of 124 AIs were normal-conducting AI, 36 were SCAI, and 3 blocked AI. The sensitivity and specificity of 3D-LGE-CMR were 95% and 91%, respectively. All risk scores showed an at best modest performance to identify SCAI (area under the curve ≤ .68). 3D late gadolinium enhancement cardiac magnetic resonance can identify SCAI with excellent accuracy and may refine non-invasive risk stratification and patient selection for invasive EAM in tetralogy of Fallot.

Fibrinolysis and clinical outcomes in acute pulmonary embolism. Madras medical college pulmonary embolism (M-PER) registry from India

BackgroundAcute pulmonary embolism (APE) is the third most common cause of vascular death. Data on APE from India and other low-and middle-income countries is sparse. ObjectivesStudy the clinical characteristics, prognostic factors, in-hospital mortality (IMH) and 12 months mortality of patients with APE in India. MethodsWe prospectively enrolled 186 consecutive patients diagnosed with APE between November 2016 and November 2021 in Madras Medical College Pulmonary Embolism Registry (M-PER). All patients had electrocardiography and echocardiography. High risk patients and selected intermediate risk patients underwent fibrinolysis. Results75 % of our patients were below 50 years of age. 35 % were women. The mean time to presentation from symptom onset was 6.04 ± 10.01 days. 92 % had CT pulmonary angiography. Intermediate risk category (61.3 %) was the more common presentation followed by high risk (26.9 %). Electrocardiography showed S1Q3T3 pattern in 56 %. 76 % had right ventricular dysfunction and 12.4 % had right heart thrombi(RHT) by echocardiography. 50.5 % received fibrinolysis. Patients with RHT received fibrinolysis more frequently (78.3 % vs 46.6 %; p = 0.007). In-hospital mortality (IHM) was 15.6 %. Systemic arterial desaturation and need for mechanical ventilation independently predicted IHM. Ten patients (5.3 %) were lost to follow up. One year mortality was 26.7 % (47/176). One year mortality of patients discharged alive was similar among high, intermediate and low risk groups(14.8 % vs 1.9 % vs 10.5 %; p = 0.891). ConclusionsPatients with PE are often young and present late in India. The in-hospital and 12 months mortality were high. Low and intermediate risk groups had a high post discharge mortality similar to high risk patients.