High-risk Status Research Articles

Impact of T-cell Receptor Status on Mutational Landscape and Outcome in T-ALL.

Impact of T-cell Receptor Status on Mutational Landscape and Outcome in T-ALL.

Assessment of gestational age using anthropometric parameters in newborns

Background: Estimation of gestational age was needed for the measurement of intrauterine growth and associated conditions, such as whether infants with a low birth weight are preterm or growth-retarded, and identifying high-risk status for developmental delay. Menstrual history was unreliable in most of the cases and ultrasound was not feasible in low resource area, so in this study we were used anthropometric measurements as a simple tool for assessment of gestational age. Methods: This study was a cross sectional observational study conducted in 380 babies born in January 2020-December 2022 in department of pediatrics, Rajah Muthiah Medical College and Hospital. The data were collected using semi-structured questionnaire and anthropometric assessment. The Epi info 7 software was used to analyse the data. Results: The mean gestational age among neonates studied was 37.06±2.32 weeks, the mean head circumference was 33.48±1.01 cm and majority of them 141 babies had head circumference 33 cm, the mean chest circumference was 30.69±1.08 cm. and majority of the babies, had chest circumference of 30 cm, the mean foot length was 7.64±0.24 cm, the mean length of the babies was 47.9±1.26 cm. Conclusions: Our study conclude that anthropometeric parameters in combination (head, chest circumference, length, foot length, birth weight) and as single parameters (foot length) was a simple and easy tool for assessing gestational age in low resource setting where we can make quick referral.

Determinants of a decline in a nutrition risk measure differ by baseline high nutrition risk status: targeting nutrition risk screening for frailty prevention in the Canadian Longitudinal Study on Aging (CLSA)

ObjectivesNutrition risk is a key component of frailty and screening, and treatment of nutrition risk is part of frailty management. This study identified the determinants of a 3-year decline in nutrition risk (measured by SCREEN-8) for older adults stratified by risk status at baseline.MethodsSecondary data analysis of the comprehensive cohort sample of the Canadian Longitudinal Study on Aging (CLSA) (n = 5031) with complete data for covariates at baseline and 3-year follow-up. Using a conceptual model to define covariates, determinants of a change in nutrition risk score as measured by SCREEN-8 (lower score indicates greater risk) were identified for those not at risk at baseline and those at high risk at baseline using multivariable regression.ResultsModels stratified by baseline nutrition risk were significant. Notable factors associated with a decrease in SCREEN-8 for those not at risk at baseline were mental health diagnoses (− 0.83; CI [− 1.44, −0.22]), living alone at follow-up (− 1.98; CI [− 3.40, −0.56]), and lack of dental care at both timepoints (− 0.91; CI [− 1.62, −0.20]) and at follow-up only (− 1.32; CI [− 2.45, −0.19]). For those at high nutrition risk at baseline, decline in activities of daily living (− 2.56; CI [− 4.36, −0.77]) and low chair-rise scores (− 1.98; CI [− 3.33, − 0.63]) were associated with lower SCREEN-8 scores at follow-up.ConclusionDeterminants of change in SCREEN-8 scores are different for those with no risk and those who are already at high risk, suggesting targeted approaches are needed for screening and treatment of nutrition risk in primary care.

Impact of minimal residual disease on relapse in childhood acute lymphoblastic leukemia: Lessons learnt from a tertiary cancer center in India

Prognostic predictive value of end of induction minimal residual disease (EOI-MRD) is well established in acute lymphoblastic leukemia (ALL). We evaluated the factors likely to affect EOI-MRD positivity (>0.01%) by flow cytometry and relapse in different BFM-95 (Berlin–Frankfurt–Munich) risk groups among children and adolescents. In this retrospective study, data of 223 newly diagnosed patients with ALL was analyzed. Association between demographic and pretreatment characteristics with EOI-MRD was assessed. Risk factors for relapse were analyzed using univariate and multivariate Cox regression. Proportion of the SR (standard risk), MR (moderate risk), and HR (high risk) patients was 18.8%, 60.9%, 20.3%, respectively. Positive EOI-MRD among these risk groups was observed in 11.9%, 18.3%, and 55.5% patients respectively (p value <.01%). MRD positivity was more likely to be associated with older age (>10 years) and BFM-HR patients (p value .0008 and <.0001). Thirty-four (15.2%) patients relapsed in the whole cohort. On univariate analysis, statistically significant factors for RFS (relapse-free survival) included hyperleukocytosis, high-risk cytogenetics, NCI (National Cancer Institute) high risk, poor day-8 prednisolone response, BFM–HR and positive EOI-MRD status. Of all these only EOI-MRD retained its impact by multivariate analysis. Positive EOI-MRD significantly predicted relapse in BFM-MR with 5-year RFS of 88.0% and 68.4% (p value .02). Five-year RFS of EOI-MRD negative and positive groups were 86.4% and 65.5%, respectively (p value .004). EOI-MRD is a powerful tool to predict relapse in children and adolescent with ALL especially in BFM-MR. Application of MRD in HR patients needs to be redefined in conjunction with other variables.

High risk of psychosis, condition or diagnosis? About a case.

IntroductionA person with “high-risk mental status (HRMS)” indicates that the person, usually young people between the ages of 14 and 25, is more likely to develop psychosis. These people have attenuated psychotic symptoms without reaching the intensity or frequency of a frank psychotic episode. It is suggested that psychological trauma could favor neurochemical and psychopathological changes in a vulnerable individual. It would be interesting to study the role of psychotherapeutic interventions in the course of high-risk mental states and their possible evolution to a psychotic disorder. We present the case of an 18-year-old adolescent whose diagnosis was high risk of psychosis.ObjectivesThis work has several objectives. On the one hand review current information on high-risk mental status (EMAR). On the other hand, develop a discussion about whether the EMAR category should be a diagnostic entity or just a condition.MethodsA bibliographic search has been carried out in the main sources of medical information such as pubmed, uptodate as well as in national and international journals. Likewise, the knowledge and clinical experience of the team has been reviewed in order to expose its own experience in this field, defining specific interventions as well as results.ResultsThe case presented is of an 18-year-old female patient.She states that the main reason for consultation is something that happened last Sunday, at which time he had “an identity crisis” in which he did not know if he was a girl or a boy. The reasoning behind this fact is that “as Pablo Alborán likes him, perhaps he is a boy”. Given the bizarreness of the explanation and the patient’s particular contact, I explore a previous psychopathological situation. She says that since last year she feels more insecure, with diffuse fear that it is difficult to specify or nominate something specific: “in class and that is very difficult for me, public presentations”, she says that “everything scares me”, she says that she has a non-specific fear that has been maintained even increasing over the months and that has led him to have greater anguish. Even though the patient dates the beginning of the picture on Sunday, it is noteworthy that the previous Thursday she had requested a consultation with psychology in the private circuit that although she does not know how to specify the reason “because of fears” it seems that the anguish resulting from this fear had been increasing, having greater difficulties for the presentations in class. The contact is psychotic and the situation that the patient describes is typical of a “treme” situation, cataloged in the current literature as a High-Risk Mental State.ConclusionsHigh-risk mental states are not a diagnostic category according to current classifications, although it is necessary to reach a consensus on what the diagnosis implies and what would be the way to proceed when a patient presents these symptoms.Disclosure of InterestNone Declared

Depression and Anxiety in Cardiac Disease, diagnosing and screening

IntroductionAmong patients with heart disease, such as coronary artery disease or heart failure, depression and anxiety disorders are extremely common. In these populations, 20% to 40% have elevated depressive symptoms, and 15% to 20% suffer from MDD. Anxiety may be even more common than depression. A recent meta-analysis suggests that over 50% of patients with heart failure have elevated rates of anxiety, and 13% meet criteria for an anxiety disorder. These prevalence rates are significantly higher than those in the general population and highlight the high-risk status of cardiac patients for these disorders.ObjectivesThe aim of this study is to highlight the frequency of anxiety and depression in patients with cardiac health problems and to explain the mechanism by which anxiety and depression influence the manifestation of cardiac diseases.MethodsΑ bibliographical review was performed using the PubMED platform. All relevant articles were found using the keywords: depression, anxiety, cardiac disease.ResultsThe links between depression, anxiety, and cardiovascular disease are complex and involve psychological, biological, and behavioral mechanisms. Depression, arrhythmias, and coronary artery disease frequently co-occur because they share common behavioral and pathophysiological drivers-unhealthy lifestyle, autonomic dysregulation, hypothalamic-pituitary-adrenal (HPA) axis dysregulation, endothelial dysfunction, and inflammation-that are intricately related to one another.ConclusionsIn patients with cardiovascular disease, depression and anxiety disorders are common, persistent, and associated with poor functional and cardiac outcomes. As such, making a timely and accurate clinical diagnosis using DSM-5 criteria is critical. Safe and effective treatments are available for the management of these disorders in patients with cardiac disease, and it is hoped that such treatment can improve psychiatric health, quality of life, and medical outcomes.Disclosure of InterestNone Declared

A History of Targeted Therapy Development and Progress in Novel-Novel Combinations for Chronic Lymphocytic Leukemia (CLL).

Over the last 10 years, the traditional treatment paradigms for CLL have been upended as the use of traditional chemoimmunotherapy regimens has declined in favor of novel targeted therapies. Targeted therapies have become the new standard of care in CLL given their superior progression-free survival (and overall survival, in some cases) when compared with chemoimmunotherapy, as well as their improved toxicity profiles. Targeted agents are FDA approved for the treatment of CLL including ibrutinib, acalabrutinib, zanubrutinib, and venetoclax. Importantly, as opposed to traditional chemotherapy regimens, the benefits of these targeted therapies appear to be consistent regardless of high-risk mutational status. In this review, we discuss the pivotal CLL studies of the last decade and the data supporting doublet and triplet novel-novel combinations. We explore the use of new surrogate end points for PFS/OS in targeted therapies such as undetectable minimal residual disease (uMRD) and their potential role in minimizing toxicity by permitting earlier treatment discontinuation. We also highlight areas that warrant further exploration and future studies that may help address some of these key questions.

Vaccine Uptake and COVID-19 Frequency in Pregnant Syrian Immigrant Women.

Immigrants have difficulties in the use of essential health services such as vaccinations. Vaccine uptake among pregnant immigrant women is very low. The aim of the study was to examine the vaccination status of pregnant immigrant women who received health services in an immigrant health center (IHC) affiliated to primary health care institutions. The research is a retrospective-designed cross-sectional type of study. The study sample consists of pregnant Syrian women who received health care from the strengthened IHC of a District Health Directorate in Istanbul between August 2020 and 2022. Age, trimesters, number of pregnancies, high-risk pregnancy status, vaccination dates and status against influenza, COVID-19 and tetanus, and vaccine types of COVID-19 were evaluated. The statistical significance level was determined as p < 0.05. None of the pregnant women had received the influenza vaccine. Of the women whose tetanus vaccine data were evaluated, 29.7% had received at least two doses of the tetanus vaccine. Of the pregnant women, 19.4% were vaccinated against COVID-19 with a minimum two doses and 4.2% had a COVID-19 infection during their pregnancy. None of the women with the COVID-19 infection were fully vaccinated against COVID-19. The vaccine uptake of pregnant immigrant women is very low. Public health interventions are needed to improve vaccination coverage among disadvantaged groups.

Exploring effects of multi-level factors on transitions of risk-taking behaviors among Bahamian middle-to-late adolescents

Adolescents experiment with risk behaviors, including delinquency, substance use, and sexual activity. Multi-level social factors, such as having high-risk peers, neighborhood risks, and parental monitoring, influence adolescents’ behaviors. We modeled transition patterns in Bahamian adolescents’ risk behaviors across three high school years and examined the effects of multi-level factors. We collected data from 2,564 Bahamian adolescents in Grade 10 and follow-ups through Grade 12. We used latent transition model to identify adolescents’ risk statuses. Further analyses used multinomial logistic regression to explore the effects of multi-level factors on assignment to those latent statuses and transitions. We identified four distinct statuses: “low risk” (47.9% of the sample at baseline), “alcohol use” (36.8%), “alcohol use and sexual activity” (5.5%), and “high risk” (9.8%). Males were more likely to be in higher-risk statuses at baseline and to transition from a lower-risk status in Grade 10 to a higher-risk status in Grade 11. Social risk factors were significantly associated with higher-risk statuses at baseline. Neighborhood risk and peer risk involvement continued to affect transitions from lower to higher risk; parental monitoring did not have a significant effect in later years. Our findings have important implications for developing targeted and developmentally appropriate interventions to prevent and reduce risk behaviors among middle-to-late adolescents.

Implications and prognostic impact of mass spectrometry in patients with newly-diagnosed multiple myeloma

Mass spectrometry (MS) is a promising tool for monitoring monoclonal protein in plasma cell dyscrasias. We included 480 transplant-eligible newly-diagnosed multiple myeloma (MM) patients from the GMMG-MM5 trial (EudraCT No. 2010-019173-16) and performed a retrospective MS analysis at baseline (480 patients) and at the pre-defined, consecutive time points after induction (444 patients), prior to maintenance (305 patients) and after one year of maintenance (227 patients). We found that MS negativity was significantly associated with improved progression-free survival (PFS) even in patients with complete response (CR) at all investigated follow-up time points. The prognostic impact was independent of established risk factors, such as the revised International Staging System. Combining MS and baseline cytogenetics improved the prediction of outcome: MS-positive patients with high-risk cytogenetics had a dismal PFS of 1.9 years (95% confidence interval [CI]: 1.6–2.3 years) from the start of maintenance. Testing the value of sequential MS prior to and after one year of maintenance, patients converting from MS positivity to negativity had an excellent PFS (median not reached) while patients converting from MS negativity to positivity progressed early (median 0.6 years, 95% CI: 0.3-not reached). Among patients with sustained MS positivity, the baseline high-risk cytogenetic status had a significant impact and defined a group with poor PFS. Combining minimal residual disease (MRD) in the bone marrow and MS allowed the identification of double negative patients with a favorable PFS (median 3.33 years, 95% CI: 3.08-not reached) and no overall survival events. Our study provides strong evidence that MS is superior to conventional response monitoring, highlighting the potential of MS to become a new standard. Our data indicate that MS should be performed sequentially and combined with baseline disease features and MRD to improve its clinical value.Clinical Trials Register: EudraCT No. 2010-019173-16

Utility of cardiac magnetic resonance feature tracking strain assessment in chronic thromboembolic pulmonary hypertension for prediction of REVEAL 2.0 high risk status.

Chronic thromboembolic pulmonary hypertension may be cured by pulmonary endarterectomy(PEA). Thromboembolic disease distribution/PEA success primarily determines prognosis but risk scoring criteria may be adjunctive. Right ventriculoarterial (RV-PA) and ventriculoatrial (RV-right atrium [RA]) coupling may be evaluated by cardiac MRI (CMR) feature tracking deformation/strain assessment. We characterized biatrial and biventricular CMR feature tracking(FT) strain parameters following PEAand tested the ability of CMR FT to identify REVEAL 2.0 high-risk status. We undertook a retrospective single-center cross-sectional study of patients (n = 57) who underwent PEA (2015-2020). All underwent pre and postoperative catheterization and CMR. Pulmonary arterial hypertension validated risk scores were calculated. Significant postoperative improvements were observed in mean pulmonary artery pressure(mPAP) (pre-op 45 ± 11 mmHg vs. post-op 26 ± 11 mmHg; p < 0.001) and PVR however a large proportion had residual pulmonary hypertension (45%; mPAP ≥25 mmHg). PEA augmented left heart filling with left ventricular end diastolic volume index and left atrial volume index increment. Left ventricular ejection fraction was unchanged postoperatively but LV global longitudinal strain improved (pre-op median -14.2% vs. post-op -16.0%; p < 0.001). Right ventricular (RV) geometry and function also improved with reduction in RV mass. Most had uncoupled RV-PA relationships which recovered (pre-op right ventricular free wall longitudinal strain -13.2 ± 4.8%, RV stroke volume/right ventricular end systolic volume ratio 0.78 ± 0.53 vs. post-op -16.8 ± 4.2%, 1.32 ± 0.55; both p < 0.001). Postoperatively, there were sixREVEAL 2.0 high-risk patients, best predicted by impaired RA strain which was superior to traditional volumetric parameters (area under the curve [AUC] 0.99 vs.RVEF AUC 0.88). CMR deformation/strain evaluation can offer insights into coupling recovery; RA strain may be an expeditious surrogate for the more laborious REVEAL 2.0 score.

Preliminary study of perceived cardiovascular disease risk and risk status of adults in small rural and urban locations in Ibadan, Nigeria.

The burden of cardiovascular disease (CVD) has been on the rise in developing countries like Nigeria recently. Studies on perceived CVD risk and the risk status of adults in Ibadan are not readily available, hence this study. A mixed-method design involving a cross-sectional survey and an exploratory qualitative study was utilized. Convenience sampling was used to recruit 418 participants (209 from rural and 209 from urban) for the cross-sectional survey, while purposive sampling was used to recruit 14 participants for the qualitative aspect. The INTERHEART risk score and the Perception of Risk of Heart Disease Scale were used to investigate participants' CVD risk status and perceived risk, respectively. The data from the cross-sectional survey were summarized by using descriptive statistics, and the data were then analyzed by using the chi-square test of association and a multiple logistic regression model, while content thematic analysis was used to analyze the qualitative data. In the rural and urban areas, respectively, 39.7% and 52.2% had a positive perception of CVD risk. In the rural and urban areas, 44% and 41.6% of individuals respectively had moderate-to-high risk of CVD. Participants with at least secondary school education [2.66 (0.61-11.53)] and participants in the urban area [2.62 (0.78-7.08)] had twice higher odds of positive CVD risk perception. Males [3.91 (1.58-9.68)], adults aged 40 and above [1.59 (0.63-4.00)] and urban dwellers [1.21 (0.33-4.39)] had higher odds of a high CVD risk status. The qualitative aspect of the study corroborated the findings from the survey, as many participants did not perceive themselves as being at risk of CVD. The majority of the participants in this study were found to have a moderate-to-high risk of CVD, and many had a negative perception of their risk. Health education and CVD prevention programs are required to curb the burden of CVD.

Delayed tracheal perforation post total thyroidectomy

Delayed tracheal perforation is a rare occurrence post thyroidectomy. We present a 72 year-old female patient that underwent elective total thyroidectomy and right upper parathyroidectomy, with bilateral central lymph node dissection and modified radical neck dissection. The post-operative period was complicated by high-risk pre-morbid status and multiple failed extubations, in addition to ischaemic tracheal areas visualised on the bronchoscopy on post-operative day (POD) 8, with subsequent computerised tomography (CT) scan showing anterior neck collections and perforation. A tracheal perforation involving the anterolateral wall (2nd and 3rd rings) was repaired surgically, followed by a tracheostomy. Suspicion of tracheal injuries should always be considered if patient fail to liberate from the mechanical ventilation post-operatively, warranting prompt conservative and/or surgical management. Potential devascularisation, secondary to diathermy-induced injury and pressure exerted by endotracheal tube cuff onto already weakened/friable trachea, should be considered as probable aetiological factors.

Fuzzy-logic-based IoMT framework for COVID19 patient monitoring

Smart healthcare is an integral part of a smart city, which provides real time and intelligent remote monitoring and tracking services to patients and elderly persons. In the era of an extraordinary public health crisis due to the spread of the novel coronavirus (2019-nCoV), which caused the deaths of millions and affected a multitude of people worldwide in different ways, the role of smart healthcare has become indispensable. Any modern method that allows for speedy and efficient monitoring of COVID19-affected patients could be highly beneficial to medical staff. Several smart-healthcare systems based on the Internet of Medical Things (IoMT) have attracted worldwide interest in their growing technical assistance in health services, notably in predicting, identifying and preventing, and their remote surveillance of most infectious diseases. In this paper, a real time health monitoring system for COVID19 patients based on edge computing and fuzzy logic technique is proposed. The proposed model makes use of the IoMT architecture to collect real time biological data (or health information) from the patients to monitor and analyze the health conditions of the infected patients and generates alert messages that are transmitted to the concerned parties such as relatives, medical staff and doctors to provide appropriate treatment in a timely fashion. The health data are collected through sensors attached to the patients and transmitted to the edge devices and cloud storage for further processing. The collected data are analyzed through fuzzy logic in edge devices to efficiently identify the risk status (such as low risk, moderate risk and high risk) of the COVID19 patients in real time. The proposed system is also associated with a mobile app that enables the continuous monitoring of the health status of the patients. Moreover, once alerted by the system about the high risk status of a patient, a doctor can fetch all the health records of the patient for a specified period, which can be utilized for a detailed clinical diagnosis.

The Association Between Comorbidities and a High-Risk Status According to COPD GOLD Groups

Objective: The natural course of the chronic obstructive pulmonary disease (COPD) is thought to be affected by the severity of COPD, frequency of episodes, as well as the presence of comorbid conditions. It was aimed to explore the effect of comorbid conditions on high-risk status in stable COPD patients. Material and methods: Study participants consisted of stable COPD patients attending to the pulmonology outpatient unit of a tertiary center between 15th May 2018 and 12th Dec 2019. Demographic data, comorbidities, clinical index scores, modified Charlson comorbidity index score (mCCI), BODE index score, and the Short Form 36 (SF-36) scores as a generic life quality measure were recorded. Global Initiative for Chronic Obstructive Lung Disease (GOLD) groups were determined based on symptoms and exacerbations. Results: There were 23(25.8%), 31(34.8%), 2(2.2%), and 33(37.1%) patients in GOLD gropus A, B, C, and D, respectively. Among these, A and B groups are considered as low-risk, and C and D groups are considered as high-risk. High risk patients had higher mCCI (p &lt; 0.001) and were more likely to have hypertension (p=0.012), congestive cardiac failure (p=0.029), chronic renal failure (p=0.022), osteoporosis (p=0.001), and anemia (p&lt;0.001). In a logistic regression analysis performed to examine the determinants of high-risk status in COPD-GOLD groups, biomass exposure was found to increase the likelihood of having a high risk-status by 3-fold. Conclusion: Classification of stable COPD patients according to GOLD groups showed higher mCCI in subjects with high-risk status. Comorbidities and mCCI did not appear to affect the high-risk status. Biomass exposure was associated with an increased risk of having a high-risk status.

Use of a device-based remote management heart failure care pathway is associated with reduced hospitalization and improved patient outcomes: TriageHF Plus real-world evaluation

Abstract Background Heart failure (HF) is a leading cause of hospital admission. However, prompt identification of worsening HF using implantable device data and proactive intervention may reduce hospitalizations. The validated TriageHF algorithm in enabled ICD/CRT devices uses sensor data to risk stratify patients for HF hospitalization in the next 30 days. TriageHF Plus is a novel device-based HF care pathway (DHFP) that uses “high” risk status as the trigger for remote intervention (see Figure 1 for pathway overview). Outcomes after DHFP implementation in a clinical setting have not been examined. Purpose To evaluate the impact of TriageHF Plus clinical pathway on hospitalisation rates. Methods A prospective, multi-center evaluation comparing monthly hospitalization rates for patients enrolled in a DHFP with a concurrent standard of care (SoC) cohort and characterizing staffing resources necessary to implement the DHFP. The DHFP cohort received telephonic assessment and guideline-directed clinical care upon transition to high-risk status. Propensity scores (PS) were applied to DHFP and SoC cohorts to allow unbiased comparison. A negative binomial model was fitted to the monthly number of all-cause hospitalizations with treatment group (DHFP vs. SoC) as a covariate, using PS as weights. Results Between 09/11/2019 and 06/24/2021, 758 patients were included in the study (443 DHFP, 315 SoC). Proportion CRT 76%/ 89% and LVEF &amp;lt;50% 78%/ 66% for DHFP/ SoC, respectively. 196 high risk transmissions prompted telephone assessment, with successful contact in 182; of which, 79 (43%) identified an explanatory acute medical issue. A secondary intervention was undertaken in 44/79 (56%). High risk transmissions took on average 19 minutes per clinical assessment (initial telephone triage and 30 day follow up). The rate of hospitalizations was 58% lower in the DHFP group, compared with SoC, after PS adjustment (IRR 0.42, 95% CI: 0.23, 0.76, p=0.004), see Figure 2. Sensitivity analyses showed Covid-19 had little effect on results. Conclusions This is the first prospective, real-world evaluation of a device-based HF care pathway to report a reduction in hospitalizations and does so with minimal staffing time. Integrated into existing HF services, device-based remote monitoring of HF patients can improve outcomes. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Medtronic

349 INTRAVENOUS CANGRELOR INFUSION IN PATIENTS UNDERGOING COMPLEX VERSUS NON-COMPLEX PERCUTANEOUS CORONARY INTERVENTION: A SUBANALYSIS OF THE ICARUS REGISTRY

Abstract Aims To compare the clinical characteristics and in-hospital outcomes of patients undergoing complex vs. non-complex percutaneous coronary intervention (PCI) with peri-procedural use of cangrelor. Methods Consecutive patients treated with cangrelor in 6 Italian institutions were retrospectively enrolled in the ICARUS (“Intravenous CAngrelor in high-bleeding Risk patients Undergoing percutaneouS coronary intervention”, NCT05505591) registry. Complex PCI was defined as any of the following: 3 vessels treated, ≥3 stents implanted, ≥3 lesions treated, bifurcation with 2 stents implanted, total stent length &amp;gt;60 mm, or chronic total occlusion. The primary endpoint was net adverse clinical events (NACE), defined as a composite of cardiovascular death, myocardial infarction, stroke, definite or probable stent thrombosis and Bleeding Academic Research Consortium (BARC) 2, 3 or 5 bleeding, at 48 hours. Secondary endpoints were assessed at 48 hours and throughout the hospital stay. Results Among 551 patients enrolled in the ICARUS registry and undergoing PCI between January 2019 and August 2022, a total of 534 (97%) patients had complete information on PCI complexity, of whom 173 (32%) underwent complex PCI and 361 (68%) underwent non-complex PCI. In general, patients with complex PCI had similar clinical features compared with non-complex PCI patients, including comparable prevalence of high bleeding risk (HBR) status according to the ARC-HBR definition (35% vs. 30%, p=0.253), but complex PCI patients presented more often with cardiogenic shock (9% vs. 2%, p&amp;lt;0.001). PCI with ≥3 stents implanted was the most frequent criterion of procedural complexity (62%). The incidence of the primary endpoint of 48-hour NACE (10% vs. 7%, p=0.264) and other clinical endpoints occurring at 48 hours or during hospitalization did not differ between complex and non-complex PCI patients. Conclusions Among patients receiving peri-procedural cangrelor, about 30% of cases underwent complex interventions. Notwithstanding higher procedural complexity, short-term clinical outcomes were similar between complex and non-complex PCI patients.

559. Inpatient Allergy Delabeling of Pediatric Patients with Low-Risk Penicillin Allergy Status through Direct Graded Oral Amoxicillin Challenge

Abstract Background Only 1% of patients with penicillin allergy are truly allergic but it remains the most common drug allergy reported. Studies show that direct oral challenge is a safe method to delabel low-risk patients using institutional screening stratification tools. There is no verified universal screening tool to perform this function, underscoring the need to address this clinical gap. This study aims to assess the efficacy of our institutional screening questionnaire at correctly stratifying penicillin allergy risk status and determine whether direct graded oral amoxicillin challenge can be safely used to delabel patients with low-risk penicillin allergy status. Figure 1Flow chart showing patient categorization based on penicillin allergy risk status and subsequent disposition following screening. Methods This was a pilot prospective study to verify penicillin allergy status among patients 3-18 years old in our institution from September 2021-March 2022. Patients were stratified using institutional screening questionnaire to no-risk, low-risk and high-risk penicillin allergy status. Low-risk patients underwent direct graded oral amoxicillin challenge using an institutional algorithm and delabeled based on their response to the testing. No-risk patients were delabeled without challenge testing. High-risk patients were referred to allergy. Results Ninety-two patients were identified with penicillin allergy. Forty (43.5%) of the 92 patients were screened using our institutional screening questionnaire. Of the 40 screened patients, 6 (15%) were identified as no-risk, 28 (70%) were identified as low-risk, and 6 (15%) were identified as high-risk. Twenty-four (86%) of the 28 low-risk patients were eligible for direct amoxicillin oral challenge. Seventeen (71%) of the 24 consented to the challenge testing but only 12 (70%) underwent direct amoxicillin oral challenge. Eleven (92%) of the 12 who underwent oral challenge were successfully delabeled. Five (83%) of the 6 no-risk patients were successfully delabeled. Three (50%) of 6 high-risk patients were referred to allergy. Overall, 16 (40%) of the 40 patients who were screened were successfully delabeled. Conclusion Our institutional risk stratification screening tool is effective at identifying penicillin allergy risk status and direct graded oral amoxicillin challenge is a safe initiative to delabel patients with low-risk penicillin allergy status. Disclosures All Authors: No reported disclosures.

Genetic Analysis of Platelet-Related Genes in Hepatocellular Carcinoma Reveals a Novel Prognostic Signature and Determines PRKCD as the Potential Molecular Bridge

BackgroundHepatocellular carcinoma (HCC) belongs to a representative lethality gastrointestinal malignancy, and comprehensive management of HCC remains intractable at present on account of its invasive biological feature that is easy to relapse and early metastasis. The intimate connection between platelets and tumor progression has been widely reported, and platelet-related indicators are also used in the clinical practice of carcinoma. This work is designed to investigate the significance of platelet-related genes in the prognostic prediction of patients with HCC and their potential role in the cross-talk between HCC cells and platelets in the tumor microenvironment.MethodsBy integrating the RNA-seq data and clinicopathological information of HCC patients, we extracted prognosis-associated platelet-related genes based on the univariate cox analysis and further established a relevant prognostic signature via the lasso cox regression analysis, and two independent HCC cohorts were used as external validation. Multiple bioinformatics methods were utilized to explore the underlying functional discrepancy between different risk groups classified by the risk model. And in vitro proliferation, invasion, and migration assays were conducted to investigate the effect of platelet stimulation on HCC cells’ viability and motility, and flow cytometric analysis was exerted to demonstrate the influence of HCC cells on platelet activation.ResultsA novel platelet-related risk model was developed and patients both in the training and testing cohorts were divided into distinct risk subgroups according to the median risk score. It was observed that the high-risk status was closely associated with poor prognosis and worse clinicopathological parameters. Meanwhile, an obvious discrepancy in the constitution of the immune microenvironment also indicated that distinct immune status might be a potential determinant affecting prognosis as well as immunotherapy reactiveness. Moreover, in vitro experiments demonstrated that PRKCD could act as a molecular bridge between tumor cells and platelets, which could either participate in regulating tumor malignant phenotype or mediating platelet activation.ConclusionsIn brief, this work reveals a novel platelet-related risk signature for prognostic evaluation of HCC patients and confirms that PRKCD is a key messenger in HCC cell-platelet interaction and plays a crucial role in mediating platelet-induced tumor progression.

Nomogram model and risk score to predict 5-year risk of progression from prediabetes to diabetes in Chinese adults: Development and validation of a novel model.

To develop a personalized nomogram and risk score to predict the 5-year risk of diabetes among Chinese adults with prediabetes. There were 26 018 participants with prediabetes at baseline in this retrospective cohort study. We randomly stratified participants into two cohorts for training (n=12 947) and validation (n=13 071). The least absolute shrinkage and selection operator (LASSO) model was applied to select the most significant variables among candidate variables. And we further established a stepwise Cox proportional hazards model to screen out the risk factors based on the predictors chosen by the LASSO model. We presented the model with a nomogram. The model's discrimination, clinical use and calibration were assessed using the area under the receiver operating characteristic (ROC) curve, decision curve and calibration analysis. The associated risk factors were also categorized according to clinical cut-points or tertials to create the diabetes risk score model. Based on the total score, we divided it into four risk categories: low, middle, high and extremely high. We also evaluated our diabetes risk score model's performance. We developed a simple nomogram and risk score that predicts the risk of prediabetes by using the variables age, triglyceride, fasting blood glucose, body mass index, alanine aminotransferase, high-density lipoprotein cholesterol and family history of diabetes. The area under the ROC curve of the nomogram was 0.8146 (95% CI 0.8035-0.8258) and 0.8147 (95% CI 0.8035-0.8259) for the training and validation cohort, respectively. The calibration curve showed a perfect fit between predicted and observed diabetes risks at 5 years. Decision curve analysis presented the clinical use of the nomogram, and there was a wide range of alternative threshold probability spectrums. A total risk score of 0 to 2.5, 3 to 4.5, 5 to 7.5 and 8 to 13.5 is associated with low, middle, high and extremely high diabetes risk status, respectively. We developed and validated a personalized prediction nomogram and risk score for 5-year diabetes risk among Chinese adults with prediabetes, identifying individuals at a high risk of developing diabetes. Doctors and other healthcare professionals can easily and quickly use our diabetes score model to assess the diabetes risk status in patients with prediabetes. In addition, the nomogram model and risk score we developed need to be validated in a prospective cohort study.