Rank P-value Research Articles

The Relationship Between Spirituality and Depression Levels in the Elderly at Graha Senior Resident Karya Kasih, Medan

Elderly individuals frequently experience declines in biological, psychological, social, and spiritual functioning, particularly those residing in orphanages who encounter considerable psychological challenges such as depression. The objective of this study is to investigate the relationship between spirituality and depression levels within the elderly population at Graha Residen Senior Karya Kasih, Kota Medan. This research employed a correlational design utilizing a cross-sectional approach. The sampling technique used was purposive sampling, with participants selected based on the criteria of being 60 or older and possessing practical communication abilities. A total of 41 respondents participated in the study. The instruments employed included the Daily Spirituality Experience Scale (DSES) and the Geriatric Depression Scale (GDS). The study found that 40 participants (97.6%) reported positive spiritual experiences, while nearly half (20 individuals or 48.8%) showed symptoms of depression. Statistical analysis revealed a significant negative relationship between spirituality and depression in older adults, with a Spearman rank p-value of 0.007 and a correlation coefficient of -0.415. In conclusion, higher spirituality is linked to lower depression levels, although depressive symptoms can still be present. The researcher recommends enhancing spirituality and suggests reminiscence therapy as a possible intervention for depression in older adults.

Evaluation and treatment response in patients with hormone receptor-positive, HER2 low metastatic breast cancer: A single center retrospective analysis.

e13158 Background: Patients with Hormone Receptor (HR)+ metastatic breast cancer have seen several new options that improve overall survival. Recently, there are new treatment options for patients with HER2 low expression (defined as HER2 1+ on IHC or 2+ on IHC with a negative FISH). Currently, patients who have HR+ metastatic breast cancer are treated with a combination of an aromatase inhibitor and a Cyclin Dependent Kinase (CDK) 4/6 Inhibitor as first line. Information regarding response to therapy in this group and a correlation with HER2 expression is limited. Methods: This is a retrospective study that aimed to evaluate patients with metastatic, HR+, HER2 low or HER2 negative breast cancer between January 1, 2015 and December 31, 2022. Patients were stratified based on their HER2 status, race, presence of de-novo metastatic disease versus progression, treatment with a CDK 4/6 Inhibitor, and time to progression (defined as the date of biopsy-proved diagnosis to the date of radiographic progression). Comparative data analyses were performed using Fisher Exact and Kruskal-Wallis testing. Kaplan Meier estimates with a log rank p-value were used for survival curves, and a P-value of < 0.05 was considered statistically significant. Results: 143 patients were included in our study. Patients were divided based on their HER2 status; 33.5% had HER2 2+ disease, 55.9% had HER2 1+, and 8.4% had HER2 0. Of the patients evaluated, 66% (94/143) were Caucasian, 25% (36/143) were African American (AA), and 9% (13/143) were of other race. There was a significant difference amongst patients treated with CDK 4/6 inhibitors when stratified by race; AA patients had a higher proportion of not using a CDK4 inhibitor (43.3% vs 20.3%; p-value 0.0109). There was a significant difference between the survival curves of HER2 0, 1+, and 2+ (log rank p-value = 0.043). HER2 0 patients progressed quicker than HER2 1+ and 2+ patients. When comparing HER2 negative and low disease, a significant difference was found between the survival curves (log rank p-value = 0.0190). In patients with HER2 low (1+ and 2+ with negative FISH) and HER2 negative disease, there was no difference noted among patients who had de-novo or progression to metastatic disease, high MiB1 status (defined as >20%), whether treatment with CDK 4/6 inhibitor was used, and tumor histology. Conclusions: In our study, patients who had any HER2 expression had a longer time to progression compared to patients with no expression. Patients who had a higher expression (2+ vs 1+) displayed a longer time to progression. This may suggest that as the HER2 expression increases, they may derive a longer benefit with first line therapy. Interestingly, African American patients had a higher proportion of not using a CDK4/6 inhibitor. Larger studies are needed to evaluate these differences and determine whether any expression can be used as a prognostic marker.

Comparing prospectively assigned trial and real-world lung cancer patients.

Aim: To evaluate the comparability of a probable clinical trial (CT) cohort derived from electronic medical records (EMR) data with a real-world cohort treated with the same therapy and identified using the same inclusion and exclusion criteria to emulate an external control. Methods: We utilized de-identified patient-level structured data sourced from EMRs. We then compared patterns of overall survival (OS) between probable CT patients with those drawn from non-contemporaneous real-world data (RWD) using a two-sided log-rank test, hazard ratios (HRs) using a Cox proportional-hazards model and Kaplan-Meier (KM) survival curves. Each regression estimate was calculated with a corresponding 95% confidence interval. We additionally conducted multiple matching methods to assess their relative performance. Results: Median (standard deviation) OS was 10.2 (0.7) months for the RWD arm and 11.3 (1.3) for the probable CT arm with a Log rank p-value equal to 0.4771. OS in both cohorts is longer than the reported CT median OS of 9.2 (0.6). The HRs generated under all five assessed matching methods (including without adjustment) were not statistically significant at the 95% confidence level. Conclusion: Our results suggest, with caveats noted, that survival patterns between real-world and CT cohorts in this NSCLC setting are not statistically significantly different.

Gene Expression Patterns Associated with Survival in Glioblastoma.

The aim of this study was to investigate gene expression alterations associated with overall survival (OS) in glioblastoma (GBM). Using the Nanostring nCounter platform, we identified four genes (COL1A2, IGFBP3, NGFR, and WIF1) that achieved statistical significance when comparing GBM with non-neoplastic brain tissue. The four genes were included in a multivariate Cox Proportional Hazard model, along with age, extent of resection, and O6-methylguanine-DNA methyltransferase (MGMT) promotor methylation, to create a unique glioblastoma prognostic index (GPI). The GPI score inversely correlated with survival: patient with a high GPI had a median OS of 7.5 months (18-month OS = 9.7%) whereas patients with a low GPI had a median OS of 20.1 months (18-month OS = 54.5%; log rank p-value = 0.004). The GPI score was then validated in 188 GBM patients from The Cancer Genome Atlas (TCGA) from a national data base; similarly, patients with a high GPI had a median OS of 10.5 months (18-month OS = 12.4%) versus 16.9 months (18-month OS = 41.5%) for low GPI (log rank p-value = 0.0003). We conclude that this novel mRNA-based prognostic index could be useful in classifying GBM patients into risk groups and refine prognosis estimates to better inform treatment decisions or stratification into clinical trials.

Trauma pain management among nurses at the Emergency and Surgical Units in a Municipal Hospital in Ghana

Introduction: Trauma pain is one of the most prevalent complaints among patients at emergency settings. Nurses have an indispensable role in the management of trauma pain, but literature has identified inadequate knowledge in pain management among nurses in many countries. This study was done to examine the practice of trauma pain management among nurses at the emergency and surgical units at the Bekwai Municipal Hospital. Methodology: This was a descriptive quantitative cross-sectional study. The convenience sampling method was employed with a structured questionnaire. Data collected were analysed with IBM SPSS Version 24. Independent t-tests and one-way ANOVA were used to examine the association between demographic characteristics and mean score in knowledge and attitude. P-values which were less than 0.05 were considered statistically significant. Results: A total of 41 nurses participated in this study. The mean score for knowledge and attitude in traumatic pain management was 51.1%. There was an association between mean score in knowledge and attitude and educational level (p-value = 0.001) and also between mean score in knowledge and attitude and job rank (p-value = 0.001). Nurses with previous training in pain management had higher knowledge and attitude (15.5± 2.7) than those without previous training (14.2± 3.5) in pain management but the mean difference was not significant (p-value = 0.182). Conclusions: Nurses at the Emergency and Surgical Unit at the Bekwai Municipal Hospital had poor knowledge and attitude toward traumatic pain management.

Pathologists’ perception of and response to their role in the management of suicide deaths in a middle-income, culturally diverse country

Introduction Pathologists through autopsies improve suicide data accuracy. Studies show that autopsy is less likely in suspected suicide than in other unnatural deaths. This work assessed Nigerian pathologists’ perception and attitude to their role in suicide management. Methods In this prospective, cross-sectional study, an online questionnaire was used to collect data from pathologists (consultants and residents) practising in our country. Results Fifty-three pathologists (20%) returned completed questionnaire; most were males (73.6%), aged from 31 – 40 year (35.8%), Christians (84.9%), of Yoruba ethnicity (35.8%) and practise in our country’s South West (39.6%). Eleven (20.8%) respondents had history of declining autopsy requests; 9 (81.8%) each identified sociocultural characteristics of society and survivors or decedents and an “obvious” cause/manner of death as reasons for declining autopsy request while 4 (36.4%) identified poor remuneration. Also, Pathologist’s demographic characteristics significantly affect their choice to perform or decline autopsy. Concerning degree of influence of identified factors, 7 (63.6%) respondents rated social circumstances around a suicide event as very strong while 4 (36.4%) rated “obvious” cause/manner of death as very weak. Twenty (37.7%) and 13 (24.5%) respondents believe that suicide diagnosis should be communicated to survivors by pathologists and police respectively. Respondents’s rank (p-value = .024) significantly affect opinion of who should communicate autopsy diagnosis while lenght of practise does not (p-value = .872). Conclusion Overall, Nigerian pathologists’ attitude to their role in suicide management is not favorable. Their performance of this role is negatively affected by social factors surrounding a suicide event.

Evaluation of a proactive cardiovascular risk screening program after preeclampsia: the Queen of Hearts study

Abstract Introduction: Despite the long-term risk for cardiovascular disease (CVD) after preeclampsia (PE), guidelines do not include specific recommendations on how to apply structural cardiovascular (CV) screening after complicated pregnancy. Insight in the prevalence of conventional CV risk factors at different age intervals may provide insight in the necessity of timely CV screening. Purpose Evaluate the prevalence of conventional CV risk factors in former pregnant women at different age intervals. Methods Data was used from the cross-sectional Queen of Hearts study, which includes relatively young women with a history of PE and a control group of women with a history of uncomplicated pregnancy. Based on history taking we established the prevalence of known diagnoses of hypertension, diabetes mellitus (DM) and hypercholesterolemia. Besides, a CV risk assessment was performed, including 30-minutes blood pressure (BP) measurement and venous blood sampling. De novo diagnosis of hypertension, DM and hypercholesterolemia were defined as systolic BP ≥140mmHg and/or diastolic BP ≥90mmHg, fasting glucose ≥7mmol/L, and Low Density Lipoprotein (LDL) >3.4mmol/L, respectively. Odds Ratio’s (ORs) with corresponding 95% confidence intervals (CI) were established, and survival analysis using Kaplan Meier curves and cox regression was performed. Results We included 1040 (39 ± 8 years) women who had suffered PE and 518 who experienced normotensive pregnancy (44 ± 8 years). In both groups, the prevalence of hypertension and hypercholesterolemia increased statistically significantly with advancing age (p-values trend <0.001), but this age-related increase seemed larger in former preeclamptic women. Across all age groups, former preeclamptic women suffered more often hypertension than controls whilst differences seemed most pronounced for younger individuals (<40 years: 12.4% vs. 2.1% respectively, OR 6.6 (95% CI 2.1-18.3); 40-49 years: 24.8% vs. 6.9% respectively, OR 4.5 (95% CI 2.4-8.3); ≥50 years: 38.2% vs. 15.7% respectively, OR 3.3 (95% CI 1.8-6.1)). A proportion of 33.5% former preeclamptic women and 23.9% controls suffered at least one CV risk factor (OR 1.6, 95% CI 1.3-2.0). This prevalence significantly increased with age, being 25.0% among former preeclamptic women aged <40 years and increasing up to 65.7% if aged ≥50 years. The age of CV risk diagnosis was on average 8 years younger in former preeclamptic women than controls, supported by survival analyses ((log rank p-value <0.001, Hazard Ratio 2.6 (95% CI 2.1-3.2)). Conclusions The prevalence of hypertension, DM and hypercholesterolemia is significantly higher in women with former PE compared to controls, already below the age of 40 and increasing with age. The age-related increase in risk was larger among former preeclamptic women than controls. Awareness on the high prevalence of CV risk factors at young age in former preeclamptic women should be taken into account when developing screening guidelines.Prevalence of CV risk factorsKaplan Meier curve CV risk factors

A proposed framework to develop nutrient profiling algorithms for assessments of sustainable food: the metrics and their assumptions matter

PurposeTo holistically assess the sustainability of our global and local food systems, we need methods that combine environmental and nutritional/health dimensions. One option is nutritional life cycle assessment in which a nutrient or health metric is incorporated into standard environmental life cycle assessment. Measuring nutritional and environmental outcomes in tandem can help elucidate new results that can aid farmers, policymakers, industry, and consumers in transitioning to a food system that is more beneficial for our planet and our health. However, the development of nutrient profiling metrics is still ongoing; thus, we develop and test, with case studies, the “points of differentiation” framework to guide the use of these algorithms in sustainability analyses.MethodsFor each of these “points” in the framework, we provide the current state-of-the-art based on the literature and then offer new insights and recommendations for their use; we do this for different food levels (i.e., production systems, food items, and diets/food supply). We provide an explicit framework for nutrient adequacy metrics, while discussing the framework’s relevance to nutrient diversity and quality metrics. We also test the “points” in this framework using case studies that examine select foods representative of a diet.ResultsBased on our review, the “points” in this framework to consider include capping, weighting, energy standardization, across-the-board versus group-specific, dietary- and/or context-specific, validation, disqualifying nutrients (e.g., saturated fat), reference amount, processing quality, selection of nutrients/ingredients, interpretation, and data quality. Based on changes in nutrient density scores and rankings, Spearman rank correlations, and Wilcoxon signed rank p-values, the “points” that have the largest effect are energy standardization, dietary specificities when assessing nutrient indices in isolation, as well as capping and disqualifying nutrients, depending on how these are applied. We hope our proposed “points of differentiation” framework can provide new insights into this quickly evolving space by offering structure to improve standardization and transparency.ConclusionThe framework provides recommendations for select “points;” nevertheless, there are still many open areas in nutritional life cycle assessment, including food functionality (e.g., processing effects, interaction factors, and bioavailability) and methodological questions related to the use of disqualifying nutrients and interpretation. Moreover, future work should focus on the role of “points” with respect to validation and differences within food groups.

Vedolizumab does not increase risk of clostridium difficile infection in patients with inflammatory bowel disease using vedolizumab: A retrospective cohort study

IntroductionSeveral studies have shown increased incidence, recurrence, and severity of Clostridium difficileinfection (CDI) over the last decade. Patients with inflammatory bowel disease (IBD) who develop CDI are more prone to morbidity and mortality than CDI in patients without IBD. This study seeks to evaluate whether IBD patients who use vedolizumab are at increased risk of CDI compared to IBD patients using other therapies. MethodsThis was a retrospective cohort study, and 684 patients with confirmed IBD (228 on vedolizumab, 228 on anti-TNF, and 228 on 5- Aminosalicylates acid therapy) were enrolled from January 2009 to August 2019 at a tertiary referral IBD center at McMaster University Medical Centre (MUMC) in Hamilton, Ontario, Canada. The primary outcome was time to the development of CDI in IBD patients using different therapies. Secondary outcomes included rates of CDI and the association between baseline variables and risk of CDI. A Cox proportional hazards (PH) model was used to evaluate baseline factors and development of CDI. ResultThere was no difference in time to CDI between the three treatment groups (log rank p-value 0.37). CDI occurred in 16 patients (2.3%), specifically four patients (1.75%) in the vedolizumab group, four patients (1.75%) in the anti-TNF group, and eight patients (3.5%) in the 5-ASA group. The Cox PH model found current smoking, older age, and concomitant immunomodulator use as risk factors for CDI, after adjustment for other covariates. Vedolizumab was not associated with increased risk of CDI in the model. ConclusionBiologic therapy with vedolizumab or anti-TNF did not impact risk of CDI. Risk factors for CDI in IBD patients included smoking, older age at the onset of medication, and immunomodulator therapy. Clinicians should have high degree of suspicion for CDI in IBD patients presenting with diarrhea, particularly in those with risk factors identified in this study.

Fluorometric Quantification of Total Cell-Free DNA as a Prognostic Biomarker in Non-Small-Cell Lung Cancer Patients Treated with Immune Checkpoint Blockade.

The present study aimed to investigate the potential of basal cell-free fluorometric DNA (cfDNA) quantification as a prognostic biomarker in advanced non-small cell lung cancer (NSCLC) patients treated with an Immune Checkpoint Blockade (ICB). A discovery and validation cohort of 61 and 31 advanced lung cancer patients treated with ICB were included in this study. Quantification of cfDNA concentration was performed before the start of the treatment and patients were followed up for a median of 34 (30-40) months. The prognostic predicted value of cfDNA was evaluated based on ROC, and Cox regression was conducted via univariate and multivariate analyses to estimate the hazard ratio. We observed that a cfDNA cut-off of 0.55 ng/µL before the ICB determines the overall survival of patients with a log rank p-value of 3.3 × 10-4. That represents median survivals of 3.8 vs. 17.5 months. Similar results were obtained in the validation cohort being the log rank p-value 3.8 × 10-2 with median survivals of 5.9 vs. 24.3. The univariate and multivariate analysis revealed that the cut-off of 0.55 ng/µL before ICB treatment was an independent predictive factor and was significantly associated with a better survival outcome. High cfDNA concentrations identify patients with advanced NSCLC who do not benefit from the ICB. The determination of cfDNA is a simple test that could select a group of patients in whom new therapeutic strategies are needed.

Teknik Effleurage Massage dan Kompres Hangat Berpengaruh terhadap Penurunan Tingkat Nyeri Afterpains pada Ibu Nifas di PMB A Kota Jakarta Selatan Tahun 2022

Introduction: The puerperium (puerperium) is a period of recovery, starting from the completion of labor until the uterine organs return such as pre-pregnancy, this postpartum period is 6-8 weeks. Some of the physiological changes that occur during the puerperium are shrinkage of the uterus which is a process in which the uterus returns to its pre-pregnancy state. In the postpartum period, there is uterine involution accompanied by contractions of the uterus so that it can cause pain during contractions or term after pain. Objectives: The purpose of this study was to determine the effect of the Effleurage massage technique and warm compresses on afterpains pain in postpartum mothers in PMB A South Jakarta City 2022. Method: This research method used a quasi-experimental approach with a pre-posttest approach, a non-equivalent control group design of as many as 30 people. The research instrument used the Numeric Rating Scale (NRS) pain scale Observation sheet. Result: The results of the study using the Wilcoxon statistical test were obtained. P-value = 0.001 < = 0.05, with a negative rank p-value in the control group 15ª and 14ª in the intervention group meaning that there is an effect of warm compresses or effleurage massage techniques and warm compresses on after-pains pain in postpartum women. Conclusion: Effleurage massage and warm compresses showed a change before or after the intervention, but the warm compress group gave a greater effect than the group given effleurage massage and warm compresses.

Perceived Health Risks among Teachers Working Remotely in the Era of Covid-19 Pandemic

The COVID-19 pandemic gained prominence and posed a threat to the traditional education system when quarantine was implemented. The teachers' workload increased as work from home was mandated. As a result of working remotely, the teachers experience challenges in their physical, mental, and socio-emotional health. This study evaluated the health risks as perceived by teachers in a tertiary educational institution working remotely during the era of the COVID-19 pandemic in terms of physical, mental, and socio-emotional health. It also aimed to describe the socio-demographic profile of the respondents and determined their current health problems. 
 
 A cross-sectional descriptive study design was utilized. The respondents were selected using a non-probability convenience sampling technique and data were collected using a researcher-made Likert-type questionnaire adapted from the Occupational Safety and Health Standards by DOLE (2022). Content and construct validity were accomplished through expert reviews and reliability testing was established through a Cronbach alpha coefficient value of 0.950. Data were analyzed using descriptive statistics as well as Z-test and ANOVA for the test of difference. The demographic profile of the respondents indicated a majority belonging to the College of Arts and Sciences, mostly of married civil status, and predominantly female with ages ranging from 41 to 50. The dominant ranks showed Instructors I, II, and III while time engagement in educational technology ranged from 3 hours and above but not greater than 6 hours. The respondents' perceived physical, mental, and socio-emotional health risks revealed a moderate risk as supported by an overall grand mean of 2.629. The physical risk was primarily associated with musculoskeletal problems and had the highest grand mean of 3.038, signifying a moderate level of risk. On the other hand, mental and socio-emotional dimensions were both perceived as low risks, with corresponding grand means of 2.525 and 2.323 respectively. Further results highlighted that level of health risks has a significant difference when grouped according to age (p-value of 0.0012) and academic rank (p-value of 0.0019), thus rejecting the null hypothesis. Sex, marital status, college affiliation, and time engagement in education technology demonstrated no significant difference at all. Health Optimization Practices for Educators (HOPE) was crafted to address health risks by promoting health and wellness through knowledge enhancement. Future studies akin to teachers’ health risks while working remotely need to be explored in the areas of ergonomics and occupational hazards.

Cardiovascular diseases among macrosomic infants of diabetic mothers

While the association between diabetes mellitus during pregnancy and cardiac morbidity of the offspring is well characterized, few existing investigations have assessed the long-term cardiovascular outcomes of macrosomic infants in specific. In this study we have examined the contributory role of diabetes on cardiac disease formation among macrosomic offspring. A population-based cohort analysis including deliveries of macrosomic infants (birthweight above 4 kilograms) between the years 1991 to 2021 at a tertiary referral hospital was conducted. Incidence of hospitalizations due to various cardiovascular conditions was compared between infants of women with and without diabetes. A Kaplan-Meyer survival curve was used to assess cumulative hospitalization incidence. A Cox proportional hazards model was used to control for confounders. Of the 16,466 macrosomic infants, 11% were of women with diabetes during pregnancy (pregestational and gestational diabetes mellitus). Offspring of both diabetic and nondiabetic mothers had comparable rates of cardiovascular-related hospitalization during childhood and adolescence (1.5% and 1.1% respectively, p=0.155; Table). Cumulative incidence of hospitalizations was similar, as shown in the Kaplan-Meyer survival curve (log rank p-value=0.246; Figure), and A Cox proportional hazards model found no association as well (adjusted HR = 1.27, 95% CI 0.82–1.95, p=0.284). In our population of macrosomic infants, diabetes mellitus does not seem to be associated with elevated rates of cardiovascular diseases.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

The Neutrophil-to-Lymphocyte-Ratio as Diagnostic and Prognostic Tool in Sepsis and Septic Shock.

Studies investigating the diagnostic and prognostic value of the neutrophil-to-lymphocyte ratio (NLR) in sepsis or septic shock commonly included preselected subgroups of patients or were published prior to the current sepsis-3 criteria. Therefore, this study investigates the diagnostic and prognostic impact of the NLR in patients with sepsis and septic shock. Consecutive patients with sepsis and septic shock from 2019 to 2021 from the prospective "MARSS-registry" were included monocentrically. First, the diagnostic value of the NLR compared to established sepsis scores was tested for septic shock compared to sepsis. Second, the diagnostic value of the NLR with regard to positive blood cultures was tested. Thereafter, the prognostic value of the NLR was tested for 30-day all-cause mortality. Statistical analyses included univariable t-tests, Spearman´s correlations, C-statistics, Kaplan-Meier analyses, Cox proportional regression analyses as well as uni- and multivariate logistic regression models. A total of 104 patients were included, of which 60% were admitted with sepsis and 40% with septic shock. The overall rate of all-cause mortality at 30 days was 56%. With an area under the curve (AUC) of 0.492, the NLR was shown to have a poor diagnostic value with regard to the diagnosis of septic shock compared to sepsis. However, the NLR was shown to be a reliable parameter to discriminate between patients with negative and positive blood cultures when admitted with septic shock (AUC = 0.714). This was still evident after multivariable adjustment (OR = 1.025; 95% CI 1.000 - 1.050; p = 0.048). In contrast, the NLR revealed a poor prognostic accuracy (AUC = 0.507) with regard to 30-day all-cause mortality. Finally, a higher NLR was not associated with an increased risk of 30-day all-cause mortality (log rank p-value = 0.775). The NLR was a reliable diagnostic tool for the identification of patients with blood culture confirmed sepsis. Yet, the NLR was not a reliable parameter to discriminate between patients with sepsis and septic shock nor between 30-day survivors and non-survivors.

Survival outcomes in adult recipients using pediatric deceased donor liver grafts. A PSM analysis from the OPTN/UNOS liver transplant registry

BackgroundThe use of pediatric donor grafts in adult recipients is a viable option to help address persistent organ shortages. Existing data is inconclusive regarding outcomes of pediatric-to-adult liver transplantation. Materials and methodsUsing the UNOS-STAR database, adults receiving a whole liver graft in the US between 2010 and 2019 were retrospectively identified. Patients were divided into two groups depending on whether they received a graft from a pediatric-donor (≤12y) or an adult-donor (≥18y). The groups were further matched using propensity-score matching (PSM) in a 1:1 ratio. Liver grafts disposition trends from pediatric donors ≤12y, as well as usage patterns of these grafts for adult recipients across UNOS regions were analyzed. The primary outcomes of this study were graft and patient survival. Secondary outcomes included LOS and need for re-transplantation. ResultsThere were 4,798 deceased donors ≤12 years during the study period. Of those, 3476 liver grafts were recovered for transplant, 203/3,476 were discarded and 3,273/3,476 transplanted. Twenty percent of those recipients were adults ≥18y. PSM created a cohort of 642 patients, (pediatric-donor group n = 321, adult-donor group n = 321). Survival analyses revealed no difference in graft survival (p = 0.64) or overall patient survival (p = 0.74) between pediatric-donor and adult-donor groups. Likewise, secondary outcomes were comparable between groups. Although not statistically significant, adults in the pediatric-donor group showed a trend toward higher rates of re-transplantation (4.4%) vs those in the adult-donor group (1.9%) (p = 0.07). A subgroup PSM analysis including only recipients with MELD score >18 further demonstrated comparable results including similar LOS, re-transplantation rates, graft failure (log-rank p-value = 0.57) and patient mortality (log rank p-value = 0.38). ConclusionPediatric-to-adult liver transplantation could represent a safe and effective option in the event that a pediatric graft is available and declined by all potential pediatric recipients, particularly if performed under careful patient selection, and in centers with pediatric liver transplant and/or LDLT. Our results are in favor of utilizing pediatric-donor livers in adult patients since there is no significant difference in mortality or graft survival and could potentially increase organ utilization by avoiding discard of these grafts.

Application of Hallmarks of Cancer Gene Signatures Reveals Novel Energetics-Associated Subtypes with Distinct Survival Outcomes in AML

Background: Acute Myeloid Leukaemia (AML) is a heterogeneous disease with a dramatic variation in patient treatment response. The treatment landscape of AML has remained relatively unchanged for over 30 years, presenting the need to further categorise the disease and it's underpinning molecular subtypes. The re-use of published and validated predictive and prognostic gene signatures provide an invaluable in silico opportunity to uncover the biological mechanisms underpinning treatment response in AML. Aims: The project aims to identify stable patient groups representative of novel molecular AML subtypes via the development of an automated analytical pipeline utilising validated gene signatures, semi-supervised techniques and survival analysis. Methods: Primary analysis was performed using a training dataset (AML-OHSU) containing 451 AML patient samples, with validation using a secondary dataset (TCGA-LAML, 200 AML patient samples). Both datasets were processed by Almac Diagnostic's ClaraT software platform which provides a comprehensive overview of tumour profiles via gene expression signatures. An automated statistical analysis pipeline was developed using Consensus Clustering, a method that provides quantitative evidence, via bootstrapping, for determining the number and membership of potential robust clusters within a dataset. This was employed using all (n = 1680) possible combinations of algorithms, distances and linkages and 167 unique gene expression signatures categorised by the 10 Hallmarks of Cancer. Clusters identified as stable were subject to further downstream analysis to identify clinical associations (log-rank p < 0.05, chi square p-value < 0.05 and BH FDR <0.2). To identify gene signatures driving cluster structure and thus survival differences, Kruskal-Wallis testing (p < 0.05) was applied using cluster labels. This was followed up with Dunn's tests (BH FDR < 0.2) to establish signature scores that were significant between all pairwise comparisons of clusters. Results The automated clustering pipeline returned a total of 1,314 stable cluster results across all algorithm, distance and linkage parameters for the 10 Hallmarks of Cancer in the AML-OHSU dataset. These stable clusters were further filtered and ranked via log-rank testing (p-value <0.05) returning 134 stable clusters with significant differences in survival outcome. Clusters based on signatures (n = 22) representative of the Energetics Hallmark most frequently occurred throughout results. Stable clusters with significant survival differences were tested against 32 clinical categorical variables present in the AML-OHSU dataset. In the highest-ranked cluster structure (k = 3, log-rank p-value: 0.033), patients associated with Cluster 3 (best survival) had both a high fusion and NPM1 mutation frequency whereas Cluster 2 (poorest survival) contained the highest number of patients above the age of 65. Out of the 22 Energetics Hallmark signatures, in n = 16, a significant difference in scores between clusters were identified. Signatures associated with Cholesterol Homeostasis, Myogenesis and Heme Metabolism were higher in the poorer survival cluster and lower in the best survival cluster. Energetics clusters and signature trends were validated in the TCGA dataset. A significant difference in survival probability (Log rank p-value: 0.019) was again found between stable clusters of the energetics hallmark (K = 3). Similarly, high signature scores in Cholesterol Homeostasis and Myogenesis signatures were again associated with the poorest survival outcome cluster. Conclusion: We have demonstrated that the novel analytical pipeline developed can aid the discovery of new molecular subtypes in AML associated with prognosis and validate these in an independent dataset. To our knowledge, the energetics hallmark has not been linked with AML prognosis before, suggesting novel biology linked to treatment response. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Clinical phenotyping of implantable cardioverter defibrillator patients to identify the association of remote device monitoring on survival benefit: a cluster analysis

Abstract Background/Introduction Over the past decade, various studies have demonstrated an association between remote device monitoring (RM) in implantable cardioverter-defibrillator (ICD) patients and all-cause mortality. However, it is unclear which clinical phenotypes account for this survival benefit. Purpose We aimed to identify clinical phenotypes within an ICD population on RM and conventional follow-up (NRM), and evaluate differences in long-term survival per clinical phenotype. Methods This is a single-center, retrospective, observational study of de novo ICD implantations (single- and dual chamber, biventricular and subcutaneous) between 2010 and 2021 in patients ≥18 years old. Data was extracted from electronic health records. Unsupervised two-step cluster analysis (TSC) was performed to identify distinct clinical phenotypes in the RM and NRM cohorts. Multinomial logistic regression analysis was performed to identify cluster characteristics, differences among the different clusters were analysed by Chi-squared test. Variable importance was evaluated for each of the 18 included clinical variables. Survival analysis was performed using the Kaplan-Meier method, log-rank was used to compare survival between groups. Results A total of 1872 ICD patients were analysed using TCS, comprising 1265 RM and 607 NRM patients, respectively. TCS for a mean follow-up duration of 5.4±3.1 years partitioned the RM and NRM groups into six clusters (Table 1). Clusters RM1 (n=444) and NRM3 (n=220) represented a predominantly primary prevention and DCM phenotype. Clusters RM2 (n=300) and NRM2 (n=173) indicated young and secondary prevention phenotypes. Clusters RM3 (n=220) and NRM1 (n=214) comprised an older, male and ischaemic cardiomyopathy (ICM) phenotype. In survival analysis 5-year cumulative incidence of mortality for the subsequent clusters was 7.4%, 4.5%, 11.6%, 41.4%, 29.8%, and 25.1%, respectively (log rank p-value &amp;lt;0.001, Figure 1). Thus, younger and DCM phenotypes (often with genetic aetiologies) experienced superior survival and high rates on RM, whereas older, male and ICM phenotypes with low rates on RM were associated with worse survival. In addition, between-group cluster-comparison of patients on RM only demonstrated important differences in long-term survival, where RM3 (comprising older, male with predominantly ICM) had poorer survival compared to young patients with a high prevalence of DCM, primary arrhythmia syndrome and low proportions of comorbidities (i.e. atrial arrhythmias, cerebral vascular accidents, diabetes mellitus). Conclusion We identify novel clinical phenotypes (clusters) of ICD patients on RM and having conventional follow-up with large differences in long-term survival. Future studies should further explore if these differences reflect benefit from RM, or the underlying natural history of each phenotype. These results may accordingly guide monitoring strategies tailored to specific ICD patient profiles. Funding Acknowledgement Type of funding sources: Public hospital(s). Main funding source(s): Public funding

Preoperative systemic chemotherapy does not benefit for appendiceal pseudomyxoma peritonei.

Pseudomyxoma peritonei (PMP) is a clinically malignant tumour syndrome mainly derived from mucin-producing appendiceal tumours. This study aimed to explore the effect of preoperative systemic chemotherapy (PSC) before cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) on the safety and postoperative survival in patients with appendiceal PMP. We performed a retrospective analysis including consecutive patients with PMP undergoing primary surgery between January, 2008 and December, 2019 in Aerospace Center Hospital. The clinical data and postoperative survival were compared between PSC group and non-PSC group. Seven hundred and fifty patients were included in the study. Significant differences were found between PSC group and non-PSC group on clinicopathological data and perioperative outcomes and the independent risk factor of serious complications was blood loss >1000 mL (P=0.026). Shorter median overall survival (OS) was found (42 months, 95% CI 31.9-52.1) in PSC group than that (67 months 95% CI 44.5-89.5) in non-PSC group. In the stratified study with PCI < 20, CC 0/1 and low-grade pathological subtype, the OS from non-PSC group was significantly better than that in PSC group (log rank P-values are <0.001, 0.006 and <0.001, respectively). Multivariate survival analysis showed that CC 0/1, HIPEC, PCI < 20 and low-grade pathological subtype were the independent prognostic factors for better OS. PSC does not increase the risk of major perioperative complications in patients with appendiceal PMP, but it also does not bring postoperative survival benefits to patients either.

Maternal anemia and long-term respiratory morbidity of the offspring-Results of a population-based cohort.

To evaluate the association between prenatal maternal anemia (hemoglobin, Hb < 11g/dl) and long-term respiratory morbidity of the offspring. A retrospective population-based cohort analysis was performed at a single tertiary medical center. We include all singletons born between 1991-2014 and discharged alive. Offspring with congenital malformations were excluded. The 3 study groups were defined on maternal Hb levels on discharge: severe anemia (< 7.0g/dl), mild to moderate anemia (7.0-11.0g/dl) and unexposed (≥ 11.0g/dl). Offspring respiratory morbidity was predefined on ICD-9 codes and recruited from the hospitalized medical records. A Kaplan-Meier survival curve was formed to compare the cumulative hospitalization and a multivariable Cox survival analysis was used to control for cofounders (gestational age, maternal age, diabetes, hypertensive disorders, post-partum hemorrhage and transfusion of blood products). 214,305 deliveries met the inclusion criteria: 807 (0.3%) mothers had severe anemia, 105,196 (49.1%) mothers had mild-moderate anemia, and the remaining were not anemic (108,302, 50.5%). Respiratory hospitalization was significantly higher among the offspring born to anemic mothers (6.2%; 5.3% and 5.1%; p = 0.020, in the study groups). However, association between maternal anemia and respiratory-related hospitalization remained significant only among the mild-moderate anemic group (adjusted Cox hazard ratio = 1.1; 95% CI 1.05-1.14; p < 0.01). The Kaplan-Meier survival analysis showed significant higher total respiratory hospitalizations in offspring according to maternal anemia status (Log Rank p-value = < .001). Maternal anemia was associated with long-term respiratory morbidity of the offspring.

P463: RE-PURPOSING OF GENE SIGNATURES IN AML UNCOVERS NOVEL ENERGETICS-ASSOCIATED MOLECULAR SUBTYPES

Background: AML is a highly heterogeneous disease with great diversity in clinical features and patient response to treatments. Despite recent improvements in disease understanding, treatments have remained unchanged for 30 years. This presents the need to characterise the disease more fully and characterise its underpinning molecular subtypes. The re-use of published and validated prognostic and predictive gene signatures e.g. Cancer Hallmarks presents an invaluable in silico opportunity to uncover the biological mechanisms underpinning treatment response in AML. Aims: To develop an automated statistical analysis pipeline combined with machine learning techniques to derive robust patient clusters representative of novel molecular AML subtypes significantly associated with clinical variables and survival outcomes. Methods: Analysis was carried out using a primary dataset (AML-OHSU: 451 AML patient samples) and a validation dataset (TCGA-LAML: 200 AML patient samples). Both datasets had been processed using Almac’s claraT platform, a software-driven solution which provides a comprehensive overview of tumour profiles using gene expression signatures. An automated analytical pipeline was developed using Consensus Clustering (CC), a method that determines the number and membership of potential clusters, using different combinations of 8 distances and 7 linkages within a dataset. Robustness was tested via bootstrapping. This pipeline was used to stratify patients via a dimension reduction approach whereby clustering was performed on 210 gene signatures categorised by 10 different hallmarks of cancer. Analysis was performed to identify clinical associations within robust clusters that were linked to differences in survival. Results: The automated clustering pipeline analysed a total of 1,314 stable clusters across 10 cancer hallmarks in the AML-OHSU dataset. Stable clusters were subsequently processed via log rank analysis (OS right-censored at 60 months) identifying 134 stable clusters with significant differences (p-value <0.05) in survival outcome. Stable clusters with significant survival differences were tested against 32 clinical categorical variables present in the AML-OHSU dataset. The results were filtered for a significant threshold (chi square p-value <0.05 and BH p-value <0.2). Here we found gene signatures representative of the Energetics hallmark, incorporating 22 signatures, to be one of the most frequently clustered throughout our results, ranking highest where K=3. A significant difference in overall survival probability (Log rank p-value: 0.033) was found between clusters (Energetics, K=3). Patients in the poorest survival cluster were characterised by a refectory induction response to treatment, having the lowest number of fusions, a low frequency of NPM1 mutations and a high proportion of patients above the age of 65. To validate energetics results from the AML-OHSU dataset, CC was again performed using gene signatures from the TCGA dataset that were representative of the energetics hallmark. A significant difference between overall survival probability (Log rank p-value: 0.019) was again found between stable clusters of the energetics hallmark (K = 3). Summary/Conclusion: We have demonstrated that a novel analytical pipeline developed here to analyse Hallmark-related gene signatures can aid in the discovery of new molecular subtypes in AML associated with prognosis. We have subsequently validated these in an independent dataset. The Energetics hallmark has not, to our knowledge, been linked with AML prognosis before, and may suggest novel biology linked to treatment response.