Favorable Category Research Articles

Utilization of Learning Media Geography of High School in Sleman Regency

This study aims to explore various aspects of learning media in geography at senior high schools in Sleman Regency, focusing on four key areas: the availability of media (including type, quantity, and condition), the utilization of media, the difficulties faced by teachers, and the efforts made to optimize media use. Utilizing a descriptive quantitative method, the research surveyed geography teachers and high school students in grades X, XI, and XII across 45 schools, comprising 17 public and 28 private institutions. A proportional random sampling technique selected 16 schools, with 16 teachers and 96 students chosen through purposive sampling. Data were collected via questionnaires, interviews, and observations, and analyzed using descriptive statistical techniques. Results revealed that the available learning media, primarily maps, atlases, and globes, were classified as insufficient in quantity, despite being in good condition. The utilization of media was in a favorable category, with a media variation of 68.75 percent. Student responses regarding media usage were high, and opportunities for engagement were also positive. However, teachers faced significant challenges, with 68.75 percent reporting difficulties related to limited media availability, manpower, costs, and time. Teachers' efforts to address these challenges were classified as moderate (87.50 percent), including organizing independent media, utilizing donations, and participating in training sessions and teacher meetings.

Adverse childhood experience, adopting a healthy lifestyle in adulthood, and risk of cardiovascular diseases

BackgroundBoth adverse childhood experiences (ACEs) and lifestyle factors have been associated with risk of cardiovascular diseases (CVDs) in later life, but whether and to what extent adherence to a healthy lifestyle in adulthood can offset the increased cardiovascular risk associated with ACEs is unclear. We aimed to determine whether and to what extent adopting to a healthy lifestyle in adulthood can offset the risk of CVDs in individuals according to their ACEs. MethodsA prospective cohort study included 143,869 participants aged 38–72 years, free of CVDs at baseline from the UK Biobank. The history of ACEs was assessed using the Childhood Trauma Screener. Participants were divided into three risk groups based on ACEs: low (no ACEs), intermediate (one or two ACEs), and high (three or more ACEs). A healthy lifestyle score in adulthood was constructed as the sum of four modifiable lifestyle factors (no smoking, adequate physical activity, healthy diet, no obesity), and participants were then categorized into three groups based on this score (unfavorable [0–1 point], intermediate [2–3 points], favorable [4 points]). Cox proportional hazard models were conducted to investigate the association between ACEs, healthy lifestyle, and incident CVDs. ResultsDuring a median follow-up of 12.49 years, 13,373 incident cases of overall CVDs were identified. This included 7521 cases of coronary heart disease (CHD), 6175 cases of atrial fibrillation (AF) and 1813 cases of stroke. Individuals with high ACEs had a greater risk of incident overall CVDs (hazard ratio [HR] = 1.39, [95%CI = 1.29 to 1.50]), CHD (1.50 [1.36 to 1.65]) and AF (1.18 [1.05 to 1.33]) compared to those with low ACEs. The risk of CVDs decreased moving from unfavorable to favorable lifestyle categories (P for trend<0.001), with the lowest risk observed among individuals with a favorable lifestyle (0.70 [0.66 to 0.74] for overall CVDs, 0.69 [0.64 to 0.75] for CHD, and 0.71 [0.65 to 0.78] for AF). Participants with high ACEs and a favorable lifestyle had a 39 %, 40 % and 47 % lower risk of developing overall CVDs (0.61 [0.48 to 0.76]), CHD (0.60 [0.44 to 0.81], and AF (0.53 [0.36 to 0.77]) than those with high ACEs and an unfavorable lifestyle. ConclusionsHaving a healthy lifestyle in adulthood could substantially attenuate the increased risk of overall CVDs, CHD, and AF conferred by ACEs.

Neutrophil-to-Lymphocyte Ratio, ESR, and CRP Have No Roles as Markers for Disease Severity and Prognosis in Patients with RRMS.

Up to now, there is no definitive prognostic factor for patients with multiple sclerosis. This study aimed to evaluate the neutrophil-to-lymphocyte ratio (N/L ratio) as a cheap, available, and noninvasive marker for disease activity and prognosis. A total of 112 patients, who were diagnosed with relapsing-remitting multiple sclerosis (RRMS), and 61 healthy controls were considered. We evaluated N/L ratio, ESR, CRP in the control, and patients in the first attack of the onset of the disease, 1 month and 6 months later during remission. All patients received interferon or Glatiramer acetate as disease-modifying therapies. The correlation of parameters with Expanded Disability Scale Score (EDSS) and Functional System (FS) involvement was evaluated. The N/L ratio was increased significantly in patients with MS in the relapse phase (mean: 2.44 ± 0.68) compared to the healthy controls (mean: 1.84 ± 0.67) (P = 0.04). Also, we found a significant increase in CRP among the aforementioned groups (P = 0.028). A significant correlation was not found between NLR, ESR, or CRP and patient's EDSS during 6 months of follow-up. For ESR and the type of functional system, a significant difference was found between favorable and unfavorable categories, while the median (IQR) of ESR in the favorable group was 7.7 (4-12) and among unfavorable ones was 13.8 (6-17.75) (P = 0.008). The results showed the effect of the innate immune system and inflammation during MS attacks. We considered that neutrophils, ESR, and CRP cannot predict disease severity or prognosis at least without a combination of other biomarkers.

Analysis Of Higher Order Thinking Skills Indicators on Physics Student Worksheet Class XI Semester II

One of the key contents of the implementation of the 2013 program is the application of learning-oriented learning to forge higher-order thinking skills. Observational results show that the student worksheet used in public high schools in Padang city is the student worksheet made by the teachers and the student worksheet released by the publisher. It is yet to be determined whether all student worksheet already contain the HOTS components required by the program. Therefore, a study on Component Analysis of Higher Order Thinking Skills (HOTS) was carried out during the student worksheet XI Semester II Physics Class at SMAN Padang City. This research is a descriptive research with a qualitative approach. The population is all worksheets for class XI senior high school physics students in semester II which are used by 16 public high schools in Padang City. The sample is student worksheet Physics SMA Class XI Semester II with the most 3 student worksheet. The research data used the student worksheet presentation analysis instrument and data collection techniques through documentation studies. Based on the analysis, it can be concluded that the Semester II Class XI Physics student worksheet used by SMAN in Padang City is of the low-facilitation and non-facilitation category. Search results for the HOTS component of student worksheet questions are in the least favorable category. The question sheets with the highest HOTS component are those with the RC-IP code student worksheet XI/II in the moderately supported category. While other student worksheet are of the low-facilitation and non-facilitation type

Farmers Perceptions towards Agricultural Insurance Schemes in Southern Rajasthan: The Case of National Agricultural Insurance Scheme (NAIS) and Weather Base Crop Insurance Scheme (WBCIS)

Crop insurance is an insurance prearrangement aiming at mitigate the financial losses suffered by the farmers due to damage of their crops due to various production risks beyond their control like natural fire, weather, floods, pests, diseases etc. Government of India started offering crop insurance in 1985, with the Comprehensive Crop Insurance Scheme. This encourages farmers to carry on with their productive efforts, which not only improves the welfare of the farmers but finally helps in stabilizing the agricultural output. In total majority of respondents, the insured loanee farmers 88 (88/150) (58.70 per cent) stated favourable attitude, while 35 (35/150) (23.30 per cent) could be found under less favourable category. The 27 (27/150) (18.00 per cent) farmers reported under highly favourable proportion. Statement wise attitude of insured loanee farmers in five-point continuum recorded most favourable attitude with mean per cent score 81.52, 78.17, 77.49 and 71.50 and placed at 1st, 2nd, 3rd and 4th respectively. This stated that the farmers can sustain natural calamities and compensation is available in time.

Analysis of the Nutritional Composition of Ready-to-Use Meat Alternatives in Belgium.

The interest in meat alternatives has increased over the years as people embrace more varied food choices because of different reasons. This study aims to analyse the nutritional composition of ready-to-use meat alternatives and compare them with meat (products). Nutritional composition values were collected in 2022 of all ready-to-use meat alternatives in Belgian supermarkets, as well as their animal-based counterparts. A one-sample t-test was performed to test the nutritional composition of ready-to-use meat alternatives against norm values, while an independent samples t-test was used to make the comparison with meat. Minced meat and pieces/strips/cubes scored favourably on all norm values. Cheeseburgers/schnitzels, nut/seed burgers and sausages contained more than 10 g/100 g total fat. The saturated fat and salt content was lower than the norm value in each category. Legume burgers/falafel contained less than 10 g/100 g protein. Vegetarian/vegan minced meat and bacon contained fewer calories, total and saturated fat, and more fibre compared to their animal-based counterparts. Minced meat and pieces/strips/cubes came out as the most favourable categories regarding nutritional composition norm values. Vegetarian/vegan steak came out the least favourable compared to steak, while vegetarian/vegan minced meat and vegetarian/vegan bacon came out the most favourable compared to their animal-based counterparts.

Karakteristik Teh Jelai (Coix Lacryma-Jobi.L) dengan Perlakuan Waktu dan Suhu Roasting yang Berbeda

Jelai (Coix Lacryma Jobi.L) seeds are grains that have the potential to be processed into herbal teas which are served either hot or cold. Jelai tea can be processed through a high-temperature roasting process to enhance the aroma and taste. Temperature and length of roasting time are factors that affect grain characteristics. The purpose of this study was to evaluate the effect of temperature and roasting time on water content, color of barley powder and the effect of temperature and roasting time on pH, total dissolved solids, and organoleptic of jelai tea. The study used a factorial completely randomized design (CRD) with two factors: (t) roasting temperature (180oC, 200oC, 220oC) and (f) roasting time (5 minutes, 10 minutes, 15 minutes). The roasting temperature and time reduced the water content of jelai powder from 11.04% to 1.57% (wb), increased the dissolved solids from 0.26 oBrix to 5.16 oBrix, and lowered the pH from 7.04-6.79. The higher the temperature and roasting time, the darker the color of the powder and the barley tea (brown), increase the burning aroma (burn aroma), nutty smelling, burn flavor and the sour taste of jelai tea. The highest results were obtained at 220oC combined roasting time of 10 minutes and 15 minutes. Overall, the level of panelist acceptance of jelai tea was in the rather favorable category for all treatments (2.77 – 3.42).

Nutritional quality and level of processing of food items broadcasted on Italian television in advertisements targeted to children

This study evaluates the nutritional quality and level of processing of food and beverage products advertised on television channels most watched by children, in Italy. Data were collected over 20 non-consecutive days from the five top channels in Italy. A total of 209 food items were analysed using the Nutri-Score and the NOVA classification. Additionally, compliance with nutritional criteria established by the World Health Organisation (WHO) and the EU-PLEDGE was assessed. Results indicate a high proportion of energy-dense and low nutritional quality foods, with 68% falling into less favourable Nutri-Score categories (C, D, and E), and 61% classified as ultra-processed by NOVA classification. When applying WHO and PLEDGE criteria, 71% and 56% of products, respectively, did not meet nutritional standards. This study underscores the low prevalence of nutritionally adequate products in food advertisements targeting children on Italian television, despite differences found based on methodological variations.

Genetic predisposition, modifiable lifestyles, and their joint effects on human lifespan: evidence from multiple cohort studies

ObjectiveTo investigate the associations across genetic and lifestyle factors with lifespan.DesignA longitudinal cohort study.SettingUK Biobank.Participants353 742 adults of European ancestry, who were recruited from 2006 to 2010 and were followed...

The Categorization of Continuous Attributes

ABSTRACTA continuous attribute (e.g., calorie count) can be classified into separate categories (e.g., high vs. low), and a similar attribute value can fall into different categories depending on where the category boundaries are drawn. This research explores the effect of categorization on judgments of options (e.g., products and incentive‐compatible games) with continuous attributes. I predict and find a systematic preference shift between two options that were presented with different categorization criteria: When two options involve a tradeoff between two continuous attributes, people tend to prefer the option with both attributes classified into the favorable categories given the categorization criteria. I further show that this effect is driven by larger perceived differences between attribute values across category boundaries and is moderated by people's tendency to rely on category information. Overall, this effect holds even when people are highly familiar with the attributes and feel confident to make similarity evaluations, when people are cued that the categories provide little informational value, and when people are incentivized to make deliberate decisions. The findings in this research carry both theoretical and practical implications.

Financial Performance Analysis at PT. Inka Multi Solusi Consulting

This research aims to assess the financial performance of the company using financial ratio analysis at PT. INKA Multi Solusi Consulting for the period 2017-2021. This research is of a quantitative descriptive type. Data analysis is carried out using financial ratio analysis, including liquidity ratios (current ratio and cash ratio), solvency ratios (debt to asset ratio and debt to equity ratio), activity ratios (fixed asset turnover and total asset turnover), and profitability ratios (return on asset and return on equity). The results of this study indicate that the financial performance of the company, as measured by the liquidity ratios, shows favorable outcomes based on the current ratio in 2020 and 2021, despite unfavorable results based on the cash ratio. Furthermore, when assessing solvency ratios using the (DAR) and (DER), the results are favorable..However, the activity ratio measured by total asset turnover is consistently decreasing, placing the company in the less favorable category. On the other hand, fixed asset turnover is in the good category. However, the financial performance for profitability ratios with return on asset and return on equity indicators indicates less favorable results

Characteristics and outcomes of out-of-hospital cardiac arrest in a hilly area: Utstein Registry data from the Nagasaki Medical Region, Japan.

To analyze characteristics and investigate prognostic indicators of out-of-hospital cardiac arrest (OHCA) in a hilly area in Japan. A retrospective population-based study was conducted using the Utstein Registry for 4280 OHCA patients in the Nagasaki Medical Region (NMR) registered over the 10-year period from 2011 to 2020. The main outcome measure was a favorable cerebral performance category (CPC 1-2). Sites at which OHCA occurred were classified into "sloped places (SPs)" (not easily accessible by emergency medical services [EMS] personnel due to slopes) and "accessible places (APs)" (EMS personnel could park an ambulance close to the site). The characteristics and prognosis based on CPC were compared between SPs and APs, and multivariable analysis was performed. No significant improvement in prognosis occurred in the NMR from 2011 to 2020. Prognosis in SPs was significantly worse than that in APs. However, multivariable analysis did not identify SP as a prognostic indicator. The following factors were associated with survival and CPC 1-2: age group, witness status, first documented rhythm, bystander-initiated cardiopulmonary resuscitation (CPR) and automated external defibrillator (AED) use, use of mechanical CPR (m-CPR) device or esophageal obturator airway (EOA), and year. Both m-CPR and EOA use were associated with a poor prognosis. In a hilly area, OHCA patients in SPs had a worse prognosis than those in APs, but SPs was not significantly associated with prognosis by multivariable analysis. Interventions to increase bystander-initiated CPR and AED use could potentially improve outcomes of OHCA in the NMR.

Composite healthy lifestyle, socioeconomic deprivation, and mental well-being during the COVID-19 pandemic: a prospective analysis

The adverse psychological and social impacts of COVID-19 pandemic are well characterized, but the role of composite, modifiable lifestyle factors that may interact to mitigate these impacts is not. The effect of socioeconomic deprivation on these lifestyle risks also remains unclear. Based on a nationally representative, longitudinal cohort, we assessed the association between a combination of pre-pandemic lifestyle factors and mental health conditions during pandemic, and the contribution of deprivation to it. Composite lifestyle factors included BMI, smoking status, alcohol consumption, physical activity, sedentary time, sleep duration, and fruit and vegetable intake, with lifestyle scores and lifestyle categories calculated for each participant. Symptoms of depression and anxiety, and personal well-being were assessed by validated scales during the pandemic. Socioeconomic deprivation was characterized by both individual-level (income, wealth, and education) and group-level factors (Index of Multiple Deprivation). Of the 5049 eligible participants (mean [SD] age, 68.1 [10.9] years; 57.2% were female) included in the study, 41.6% followed a favorable lifestyle, 48.9% followed an intermediate lifestyle, and 9.5% followed an unfavorable lifestyle. Compared with favorable lifestyle category, participants in the intermediate and unfavorable lifestyle category were at increased risk of mental health conditions, with the hazard ratio (HR) for trend per increment change towards unfavorable category of 1.17 (95% CI 1.09–1.26) for depression, 1.23 (1.07–1.42) for anxiety, and 1.39 (1.20–1.61) for low well-being. A significant trend of lower risk for mental health conditions with increasing number of healthy lifestyle factors was observed (P < 0.001 for trend). There were no significant interactions between lifestyle factors and socioeconomic deprivation for any of the outcomes, with similar HRs for trend per one increment change in lifestyle category observed in each deprivation group. Compared with those in the least deprived group with favorable lifestyle, participants in the most deprived group adherent to unfavorable lifestyle had the highest risk of mental health outcomes. These results suggest that adherence to a broad combination of healthy lifestyle factors was associated with a significantly reduced risk of mental health conditions during the COVID-19 pandemic. Lifestyle factors, in conjunction with socioeconomic deprivation, independently contribute to the risk of mental health issues. Although further research is needed to assess causality, the current findings support public health strategies and individual-level interventions that provide enhanced support in areas of deprivation and target multiple lifestyle factors to reduce health inequalities and promote mental well-being during the ongoing COVID-19 pandemic.

Influence of the cytoprotective drug meldonium on diastolic dysfunction of the myocardium

Background: The use of myocardial cytoprotectors (meldonium) in patients with exertional angina is a scientific-practical dilemma. Material and methods: An open randomized clinical trial was conducted involving 160 patients with chronic heart faliure (117 men and 43 women) aged 37 to 81 years. Of them, 142 patients had angina pectoris of stable effort from different functional classes, and 21 – unstable angina pectoris. Study groups were comparable according to the frequency of indication of background drugs and meldonium. Results: The number of patients with normal diastolic function in both groups, but with a net superiority to meldonium combination administration, has considerably increased: 41 patients (91.11%) in group II vs 33 (58.93%) in the group treated with basic treatment after 9 months of medication; 43 patients (95.56%) group II vs 36 (64.29%) in group I at 12 months of medication. During this period, no patients with pseudonormal type of diastolic dysfunction were registered, these passing into a ”more” favorable category – delayed relaxation. Conclusions: The data obtained confirmed the benefit of using cardiocitoprotection in inducing the reverse-remodelling of the myocardium of left ventricle regardless of the initial ventricular geometric pattern, but the administration of mildronate combination demonstrated a significantly superior efficiency to the basic treatment in hypertrophy of left ventricle regression, an event notable towards the end of the research period.

Acute myeloid leukemia with t(16;21)(q24;q22), CBFA2T3::RUNX1, in post-treatment setting, a case report

Abstract Introduction/Objective Acute myeloid leukemia (AML) with t(16;21)(q24;q22), CBFA2T3::RUNX1 is an uncommon entity that has been reported in both pediatric and adult patients as de novo AML or secondary to prior chemo/radiation therapy. CBFA2T3::RUNX1 AMLs share similar clinico-pathological features and gene expression profile with RUNX1::RUNX1T1 AML. Methods/Case Report We report a case of AML with CBFA2T3::RUNX1 in a 52 year old female who had history of small cell cervical cancer treated with chemotherapy (4 cycles of cisplatin and etoposide) and pelvic radiation therapy. About 17 months after completion of therapy, she presented with anemia and thrombocytopenia, normal WBC/neutrophil count, eosinophilia and increased blasts (up to 10%) in blood. Bone marrow biopsy shows AML with maturation (FAB-M2), erythropoiesis is present, whereas megakaryocytes are decreased. Flow cytometry analysis shows myeloblasts with aberrant CD19 and CD56 expression; in addition, increased CD117/tryptase positive cells are noted, mostly interstitial and more concentrated around bone trabeculae. By immunohistochemical stains, these cells are at least partially positive for CD25, negative CD2, CD30. Karyotype studies demonstrate t(16;21)(q24;q22) and trisomy 8 in all metaphases. FoundationOne heme NGS studies confirmed CBFA2T3::RUNX1 fusion, and no additional mutations were identified. Patient received induction chemotherapy with Idarubicin/Cytarabine plus GO (Gemtuzumab ozogamicin); day 14 bone marrow showed chemotherapeutic effect and she is now in morphologic remission 5 months after diagnosis. Results (if a Case Study enter NA) NA Conclusion Our case adds to the limited knowledge of CBFA2T3::RUNX1 AMLs. Our case shows morphological and immunophenotypic features similar to AML with RUNX1::RUNX1T1, with unusual presentation of peripheral eosinophilia, and increased CD117/tryptase positive cells in bone marrow, the latter has been reported occasionally in core binding factor AMLs. We emphasize the importance of comprehensive genetic studies in AML patients, lack of adverse genetic abnormalities in our patient indicates favorable risk category regardless of the post-treatment clinical setting.

Selected Genomic Structural Variants Refine ELN-Based Prognostic Stratification of Patients with Acute Myeloid Leukemia and Normal Karyotype

Background. Normal karyotype Acute Myeloid Leukemia (nk-AML) accounts for 40% of all AML. Conventionally, nk-AML patients (pts) have been associated with the ELN favorable and intermediate risk category, characterized by extreme prognostic heterogeneity, representing an unmet therapeutic need especially as regards effective positioning of allogeneic transplantation (ASCT) as consolidation treatment. Aim. To improve risk stratification of nk-AML, on top of 2017 ELN criteria, by identification of structural variants (SV) with prognostic significance through the analysis of whole genome sequencing by long reads Nanopore platform. Patients and Methods. A total of 247 nk-AML pts receiving intensive therapy was included. The learning cohort included 95 pts from the prospective NILG 02/06 trial ( Bassan R Blood Adv 2019; 3:1103) comparing standard vs high-dose chemotherapy and 67 pts from the prospective GIMEMA AML1310 trial of risk-adapted, MRD-directed therapy ( Venditti A, Blood 2019;134:935). The validation cohort comprised 85 pts from Florence database. Whole genome long-read nanopore sequencing was performed on GridION platform to a median depth of 5x. After alignment to hgr38 genome, only those SV that had been concurrently identified by 4 independent callers were retained for analysis. Results. In the whole series (WS),197 pts (79.7%) obtained CR, 91 (46.2%) relapsed; 50 pts (20.2%) were primary refractory, 83 (33.6%) underwent ASCT. According to ELN criteria, 56.7%, 29.2% and 14.1% of the pts were in the favorable, intermediate and adverse risk category. Median survival (OS) was 16.9mo (9-24.7) in adverse risk category, 24.1mo (4.5-43.7) intermediate, and not reached in favorable risk category (P= 0.00007). However, adverse and intermediate category did not differ significantly (P=0.63), as expected considering the selection of nk-AML. Extensive filtering against 100 healthy donors and publicly available datasets of genomic variants to remove SV with &amp;gt;0.01% allele frequency resulted in 2,038 SV; after removal of private SV (ie, present in ≤2 pt), 122 SV were finally retained. Univariate regression analysis resulted in 10 SV associated with OS, of which 7 were validated with independent technology (Sanger and high-resolution melting, HRM). Multivariate analysis including all ELN-risk score variables showed that 5 of the 7 SV were independently associated with OS (hence, referred as high-risk variants, HRV). Three HRV affected the locus of coding genes on Chr4 q32.3 (inversion spanning 6,103bp), Chr5 p12 (333bp insertion) and Chr9 q34.3 (57bp deletion); Chr3 q26.1 (64bp insertion) in a Long Intergenic Non-Protein Coding RNA gene; Chr2 p13.2 (64bp deletion), in intergenic region. Presence of HRV impacted on OS with HR of 4.1 (95%CI,2.4-7; P=1.5e-7) in the learning cohort and HR 3.4 (95%CI, 1.5-7.6; P=0.003) in the validation cohort. Censoring at ASCT had no impact in either cohort. In total, 29 pts (11.7%) were HRV+, and their OS was 12.6mo (95%CI, 5.4-19.9) vs not reached (95%CI, 33.5-40.9; P=8.4183e-11) in HRV- pts (HR 3.9, 95%CI, 2.5-6; P=1.6261e-9) (Figure 1). DFS and EFS was 7mo (95%CI: 3.6-10.5) and 14.6mo (95%CI,2.1-27) in HRV+ pts vs not reached (95%CI, 31.7-40) and 30mo (95%CI: 29.9-30.1) (P&amp;lt;0.01 for both). Also, the rate of relapse was higher among HRV+, 58.6% vs 34.4% (P=0.01), with a trend to lower rate of CR attainment (72.4% vs 82.6%). There was no remarkable difference between HRV+ and HRV- pts as regarded frequency and type of ELN molecular variables. We finally evaluated whether integration of HRV within ELN risk score might improve the predictive performance of the latter. The resulting model enlisted 4 tiers, favorable (median OS not reached), intermediate (27.4mo, 95%CI: 3.6-51.1, HR:2.4; 95%CI,1.5-3.8), adverse (21.5mo, 95%CI: 5.4-37.6, HR:2.5; 95%CI,1.4-4.3) and HRV+ (12.6mo, 95%CI: 5.4-19.9, HR:5.9; 95%CI,3.6-9.8) categories (P=1.3395e-12) (Figure 2). Of note, the HRV+ category included 79.3% of pts otherwise categorized as ELN favorable or intermediate. Conclusions. We have identified, by long-read whole genome sequencing, a set of 5 structural variants that marks a subgroup of nk-AML pts with outmost dismal prognosis and may be integrated in ELN-risk score to help therapeutic decisions. Since HRV can be conveniently interrogated by routine approaches such as Sanger sequencing and HRM, further studies on larger cohorts might support these findings.

Feasibility and Relevance of Incorporating Genetic Testing By Next-Generation Sequencing for Acute Myeloid Leukemia Patients Treated in Low- and Middle-Income Countries

Background: The outcome of the treatment for acute myeloid leukemia (AML) in low- and middle-income countries (LMIC) is significantly worse than in high-income ones due to several factors, including higher non-relapse mortality from infections and limited access to hematopoietic stem-cell transplantation (HSCT). In this resource-constrained setting, AML-risk stratification is based exclusively on cytogenetics, which has longer turn-around time and higher failure rates compared to next-generation sequencing (NGS). Here, we report the benefit of adding a simplified NGS gene panel to improve risk stratification for 279 adult Brazilian patients with AML (male=146, female=136; mean age=50 years; range 18-65) included in International Consortium of Acute Leukemia (ICAL) 2015 Study. Material &amp; Methods: Samples from 10 ICAL centers were shipped to the National Central Lab at the University of São Paulo at Ribeirão Preto Medical School, Brazil (located zero to 1420 kilometers from centers). All patient samples were assessed by conventional cytogenetics and molecular tests by RT-PCR for RUNX1::RUNX1T1 and CBFB::MYH11 , PCR and fragment analysis for NPM1 and FLT3-ITD allelic ratio, and Skyline AML profiler assay for CEBPA double mutant. We retrospectively searched for mutations in the ASXL1, CEBPA, FLT3, IDH1, IDH2, NPM1, RUNX1, TP53 genes using NGS in 53 out of the 279 samples. The tests were performed in the Illumina iSeq100 Sequencing System using reagents and methodology developed under the supervision of the Erasmus MC Cancer Institute (Valk Laboratory) as part of the activities of the ICAL Laboratory Subcommittee. Training, including bioinformatics analysis, was provided virtually and through a short-term visiting program (ASH Visitor Training Program) to Erasmus MC. Datasets with genetic testing results obtained locally were sent and reanalyzed at Erasmus MC and discussed in bi-monthly meetings. Risk stratification was determined either by cytogenetics only or by cytogenetic and molecular analysis according to the ELN 2017 proposal. Overall survival (OS) was defined from date of diagnosis to last follow up or death and compared by Kaplan-Meier and Log-Rank test followed by Benjamini-Hochberg p-value adjustment method, using R 4.3.1. Results: conventional cytogenetics was informative in 68% (190/279) of the cases, and based on those results 32 (16.8%), 116 (61%) and 42 (22.1%) patients were stratified into favorable, intermediate and adverse categories, respectively. However, no significant difference in the OS was detected according to cytogenetic risk. When genetic testing by NGS was added, 54 (27.3%), 98 (49.5%) and 46 (23.2%) patients were assigned into favorable, intermediate and adverse categories, respectively. Twenty-six (48%) patients had risk re-classified as a consequence of the NGS results. Moreover, two out of four patients whose risk stratification could not be assigned due to insufficient metaphasis were classified based on NGS results. Of note, the median OS of the favorable group was significantly longer (not reached) than that of intermediate and of the adverse groups (6 months), ( p&amp;lt;0.0001), but no difference was detected between the latter two. We also assessed whether genetic testing by NGS would change the risk category of AML patients previously classified based on conventional cytogenetics in association with the evaluation of gene rearrangements, NPM1, FLT3 and CEBPA mutational analysis by methods other than NGS. NGS results changed the category of 3 out of 54 patients. Our results indicate the feasibility of developing a simplified platform of genetic testing for AML based on NGS in LMIC, which was able to improve the identification of favorable-risk patients and may help to better allocate resources.

Real-World Validation of the European Leukemia Network 2022 Risk Stratification in Acute Myelogenous Leukemia

Background: The 2017 European LeukemiaNet (ELN 2017) guidelines have become foundational for the risk stratification, prognostication, and treatment of acute myelogenous leukemia (AML). The updated 2022 European LeukemiaNet (ELN 2022) guidelines include additional cytogenetic abnormalities and genetic mutations for risk group assignment. It remains unknown how these updated guidelines compare for risk stratification and prognosis. Methods: We studied (N=287) adults with newly diagnosed AML from MedStar Georgetown University, MedStar Washington Hospital Center, and Baylor University Medical Center from 2012 to June 2023. Patients were stratified as favorable (fav), intermediate (int), or adverse (adv) risk according to ELN 2017 and ELN 2022 criteria. Overall survival (OS) was compared by age, race, and sex. Statistical analysis performed with SAS. Results: Median age was 65+16 years with a predominance of males (N=168, 59%). African-Americans (AA) composed 15% (N=44) of the cohort. Myelodysplastic-related mutations were present in 33 patients (15%), whereas the prevalence of epigenetic mutations was 25% (N=55). By ELN 2017 criteria, 19 (7%) patients were characterized as fav, 64 (23%) as int, and 198 (70%) as adv risk. Using ELN 2022 criteria, 18 (6%) patients were categorized as fav, 52 (19%) as int, and 211 (75%) as adv risk. Kaplan-Meier (KM) curves revealed a median overall survival of 200 days (d), 400 d, and 1532 d in the adv, int, and fav risk groups, respectively (log-rank p&amp;lt;0.001) by ELN 2017 criteria. Median OS was 379 d, 527 d, and 1552 d for the adv, int, and fav groups, respectively (log-rank p&amp;lt;0.001) in the ELN 2022 cohort. Stratifying by age &amp;lt;60 years, median OS was 390 d in the adv group and 832 d in the int group (log-rank p=.021)by ELN 2017 criteria,as compared to 350 d in the adv group and 757 d in the int group (log-rank p=.0012) by ELN 2022 criteria.Among those &amp;gt;60 years of age, median OS was 244 d and 349 d in the adv and int groups, respectively by ELN 2017 criteria (Anova p&amp;lt;0.25). In the ELN 2022 cohort, median OS among those &amp;gt;60 years of age was 284 d for the adv group and 209 days in the int group (Anova p&amp;lt;0.62). Among females, median OS in the adv group was 224 d and 342 d in the int group by ELN 2017 criteria (Anova p=0.4). In the ELN 2022 cohort, median OS among females was 214 d in the adv group and 421 d in the int group (Anova p=.13). Median OS among male patients in the ELN 2017 cohort was 324 d for those of adv risk and 623 d for those of int risk (Anova p&amp;lt;0.004). In the ELN 2022 cohort, median OS in males was 352 d and 563 d in the adv and int groups, respectively (Anova p&amp;lt;0.07) . In the ELN 2017 cohort, median OS was 259 d in AA patients as compared to 719 d in non-AA patients; this was not statistically significant (Anova p=0.16). Comparatively, in the ELN 2022 cohort, median OS for the AA patients was 153 d as compared to 212 d for the non-AA patient population (Anova p=0.86) .Conclusions: In this real-world dataset, the updated ELN 2022 guidelines reproduce differential survival for proposed favorable, intermediate, and adverse risk categories. When considering time to endpoint survival [Kaplan Meier curves] in our study, ELN 2022 seems to lack the ability to clearly discriminate among the adverse and intermediate risk subgroups. It is possible that patients seen in academic institutions not participating in FLT3 directed therapy trials retained inferior survival whereas similar patients fared better through early enrollment in trials using molecular targeted therapy. Finally, neither ELN 2017 nor ELN 2022 discriminate survival in AA populations for either adverse or intermediate subgroups. Efforts should be directed to develop novel risk stratification schemas to better encapsulate this vulnerable population.

Applicability of SIE/Sies/GITMO Fitness Criteria to Therapy-Related and AML-MRC Receiving CPX-351: Results from a Large, Retrospective, Multicentric, Observational Study

Introduction: Treatment of therapy-related AML (t-AML) and AML evolving from an antecedent myelodysplastic syndrome (AML-MRC) represent a clinical unmet need being characterized by an unfavorable outcome. Among the emerging treatment options, CPX-351 has been approved by Regulatory Authorities for the treatment of fit patients (pts) affected by these AML sub-types. Although patented for the treatment of pts fit for intensive chemotherapy, in real-life CPX-351 is also administered to unfit ones, raising the case of tolerability in these categories. Among scores for fitness definition, SIE/SIES/GITMO criteria were extensively validated in large cohorts of AML pts receiving intensive chemotherapy and are increasingly incorporated into clinical trials. However, since these criteria have not been tested yet in the subset of t-AML and AML-MRC, we investigated their applicability in these pts receiving CPX-351. Methods: Patients classified as t-AML or MRC-AML according to WHO2016 classification receiving at least one cycle of CPX-351 were included in the present analysis. Genetic and cytogenetic data were classified according to ELN2017 risk stratification. SIE/SIES/GITMO criteria were retrospectively applied to the whole series to categorize pts as fit or unfit to intensive chemotherapy (Ferrara et. al, Leukemia 2013), aiming at evaluating early-death rate and overall survival (OS). We also verified if ELN2017 risk-stratification might provide further information about long-term outcome, independently of fitness assessment. Results: This retrospective study includes 398 pts with t-AML (19.3%) or AML-MRC (80.7%) enrolled from 29 Italian Institutions between 2018 and 2023. Median age was 65 years (range 32-79), with a slight male prevalence (56.8%). According to SIE/SIES/GITMO criteria, 323 (81.2%) pts qualified as fit and 75 (18.8%) as unfit. Based on ELN2017 risk stratification, 17 (4.3%) pts were classified as favorable, 162 (40.7%) as intermediate, 217 (54.5%) as adverse risk. Only 2 (0.5%) pts were not classifiable due to incomplete genetic data. No differences were observed in terms of ELN2017 risk distribution among the fit and unfit groups. After first induction, 188 of 323 (58.2%) fit and 42 of 75 (56%) unfit pts achieved a complete remission (CR), for a total of 230 (57.8%) pts entering CR. From CPX-351 start, 18 and 55 deaths at 28 days and at 100 days occurred, respectively. Early death rate at these early timepoints statistically differed between the two groups (3% vs. 10.7% at 28 days and 10% vs. 28% at 100 days for fit and unfit pts respectively; p&amp;lt;0.05). No excess of mortality was observed for unfit patients at any timepoint after 100 days from first CPX-351 induction. Competitive risk analyses showed no differences in terms of early death by relapse between the two groups. With a median follow up of 24 months, unfit pts were characterized by a significantly shorter OS as compared to fit ones (median OS of 8 months [CI 95%: 4.1-11.8] and of 18 months [CI 95%: 14.7-21.1] for unfit and fit pts, respectively; p&amp;lt;0.0001) [Figure 1]. When stratified according to genetic/cytogenetic, median OS of fit pts was commensurate with ELN2017 risk (median OS not reached vs 20 months vs 13 months for favorable vs intermediate vs adverse risk, respectively; p &amp;lt; 0.01), whereas no differences in median OS were observed between favorable, intermediate, and adverse categories in unfit pts (median OS of 20 months vs 11 months vs 7 months, respectively; p=NS). Conclusions: In our real-life analysis, we demonstrated that fitness assessment according to SIE/SIES/GITMO criteria identifies populations with discrete outcome among t-AML and AML-MRC pts receiving CPX-351. In unfit patients, outcome prediction seems independent from ELN 2017 risk stratification. Fit and unfit groups achieved similar CR rates but different long-term OS. Such discrepancy can be justified by the higher early mortality observed among unfit pts that translated into shorter long-term survival. In a future perspective, modulating CPX-351 schedule in this group may be a reasonable option to spare toxicity without giving up the opportunity to deliver curative-intended therapies.

Real World Outcome of Unfit Patients with Acute Myeloid Leukemia Treated with the Combination Venetoclax Plus Hypomethylating Agents in the Gimema AML2320 Observational Trial

Introduction: Based on the results of the phase 1b (NCT02203773) and phase 3 (VIALE-A; NCT02993523) studies, venetoclax (VEN) in combination with hypomethylating agents (HMAs) was approved by FDA and EMA for the treatment of patients (pts) with newly diagnosed (ND) acute myeloid leukemia (AML) who are ineligible for intensive chemotherapy (IC) or whose age is 75 years or more. In particular, in the VIALE-A trial the association Ven+Azacitidine (AZA) has proven to induce rapid and durable remissions, with a median overall survival (OS) of 14.7 vs 9.6 months of pts enrolled in the placebo+Aza arm. The GIMEMA 2320 Trial (NCT04589728) is a prospective, observational study intended to investigate the outcome of pts treated with the combination Ven+HMA, in a real-world setting. Methods: Pts not candidate to IC because of age (≥75 years), performance status (PS) or comorbidities according to the SIE/SIES/GITMO (Ferrara) criteria, were eligible to the AML2320 trial and to receive the combination HMA plus venetoclax. VEN (400 mg a day, orally, day 1-28), AZA (75 mg/m 2 a day, day 1-7) and Decitabine (DEC) (20 mg/m 2 a day, day 1-5) were given at conventional doses during a 28-day cycle. Evaluation of OS was the primary end-point of the trial; response rate, time to response, event free survival (EFS), disease free survival (DFS), cumulative incidence of relapse (CIR), and safety profile were secondary end-points. Results: From November 2020 to December 2021, 188 pts were enrolled to the observational trial with 178 being evaluable at the time of this analysis. Ninety-six (54%) males and 82 (46%) females; median age 74 years (49-85) with 74 (42%) pts being 75 years old or more. One-hundred and 20 (68%) pts had “ de novo” AML and 58 (32%) secondary AML. In pts below the age of 75 years, reasons that contraindicated exposure to IC were: pulmonary diseases (6%), active infections poorly controlled with antibiotic therapy (5%); cardiac ejection fraction &amp;lt; 50% (4.5%), ECOG PS ≥ 3 not related to the underlying AML (4%); psychiatric illnesses requiring specific therapy (3%). In 54% of the pts below the age of 75, there was also a miscellanea of other conditions which physicians recognized as incompatible with IC. ELN2017 risk-category assignment was feasible in 151 pts with 34 (23%), 69 (46%) and 48 (32%) belonging to the favorable, intermediate and adverse category, respectively. One-hundred and 34 (75%) pts received VEN+AZA and 44 (25%) VEN+DEC. The median no. of delivered courses was 5 (1-27). Eleven (6%) pts were submitted to an allogeneic stem cell transplant after having received 4 courses of VEN+HMA and being in CR/CRi. After the first course, response assessment was evaluated in 123/178 (69%) pts with 70 (57%) being in CR/CRi. One-hundred and 53 pts were given a second course, and response assessment was available in 73; at this stage, 47/73 (64%) were in CR/CRi. With a median follow-up of 19.9 months, the median OS for the whole population is 14.2 months (12.4-18.4) (Figure 1A) and the median DFS 13.7 months (10-NR) (Figure 1B). One- and 2-year OS is 58% (51%-67%) and 33% (26%-43%), respectively; 1- and 2-year DFS is 53% (42%-67%) and 44% (33%-59%), respectively. No significant differences were found in OS and DFS when the survival analysis was split by age (&amp;lt; or ≥ 75 years). Median OS for favorable-, intermediate- and adverse-risk category was 24.5 months (14.2-NR), 15.4 months (11.9-NR) and 8.9 months (6.8-13.4), respectively. Median DFS for favorable-, intermediate- and adverse-risk category was NR (10.8-NR), 14.1 months (8-NR) and 9.9 months (3.2-NR), respectively. Conclusions: To our knowledge this is one of the largest series of pts with AML treated with VEN+HMA in a real-world setting. With all the limitations of a data collection still to implement, we reported for this Italian cohort of pts a median OS that is similar to that observed in the VIALE-A study (14.2 vs 14.7 months); also, our median follow-up is similar to the one of the VIALE-A study, at the time of its publication (19.9 vs 20.5 months). This real-life experience confirms that the combination VEN+HMA is an effective treatment for a very difficult to treat population of pts. This analysis also denotes the need for educational activities intended to sensitize physicians towards a more appropriate and timely evaluation of response; indeed, a sizeable proportion of Italian hematologists still approach assessment of response to VEN+HMA the same way they did when using HMA alone.