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Abstract Prognosis in acute myeloid leukemia (AML) patients is influenced by various factors, most importantly, patient clinical status and cytogenetic/molecular abnormalities. Within those factors, elevated lactate dehydrogenase (LDH) is considered a poor prognostic indicator in AML patients. Our study aims at exploring the different factors associated with elevated LDH and their impact on overall survival (OS). After obtaining IRB approval, we reviewed the charts of 381 AML patients diagnosed at Mayo Clinic, Rochester, between the years of 2016 and 2023. All data was recorded at the time of AML diagnosis. Patients with no cytogenetic and molecular data were excluded from this study. LDH levels were recorded if measured within 10 days of diagnosis and treatment for AML was not yet given. Both risk stratification and response evaluation were done following the 2022 European LeukemiaNet (ELN) guidelines. OS was calculated from the date of AML diagnosis to the date of last follow-up or death. We used BlueSky Statistics V 10.3.4 for statistical analysis. We identified 299 patients (78.4%) who had elevated LDH levels (normal ≤ 222 U/L) at the time of diagnosis with a median of 417 U/L (range, 223-7989). The median age for those patients was 68 years (range, 18-94), with 78 (26.1%) of them having a prior myeloid disease (MDS, MPN, or MDS/MPN) before AML diagnosis. By risk stratification, more than half of the patients had an adverse risk profile (n=171, 57.2%), while 71 (23.7%) and 57 (19.1%) had an intermediate and favorable risk, respectively. Most of those patients had an abnormal karyotype (n=204, 68.7%), with complex karyotype (n=103, 34.7%) being the most common abnormality, followed by monosomy 7 (n=50, 16.8%) and trisomy 8 (n=46, 15.5%). Next-generation sequencing (NGS) was performed on 268 (89.6%) patients with elevated LDH, and the most common mutations were TP53 (n=60, 22.3%), FLT3-ITD (n=59, 21.1%), and NPM1 (n=51, 18.5%). TP53 mutations were more common in patients with normal/low white blood cell count (WBC) in contrast with FLT3 and NPM1, which were the most common mutations in patients with high WBC. After grouping the patients according to their LDH levels (group 1: 223-444 U/L, group 2: 444-666 U/L, group 3: > 666 U/L), we found that FLT3-ITD mutations were more likely to occur at higher LDH levels i.e. groups 2 and 3 (p= 0.002). The majority of patients with elevated LDH (n=262, 87.6%) received therapy following diagnosis, with the most common treatment regimens being a combination of a hypomethylating agent and venetoclax (HMA+VEN) (n=97, 37%) and a (7+3)-based induction therapy (n=77, 29.4%). When comparing patients with elevated LDH (n=299, 78.4%) to patients who had non-elevated LDH (n=82, 21.5%), no difference in both median age at diagnosis and risk stratification was found. We noticed an increase in WBC (median, 7.7 vs. 2.1) (p<0.001) along with an increase in peripheral blasts (median, 28% vs. 7%) (p<0.001) in elevated LDH patients. Among patients with non-elevated LDH, 21% (n=17) had a complex karyotype compared to 34.7% (n=103) in the elevated LDH group (p=0.022). The molecular profile was different between the 2 groups, where the most common mutations in patients with non-elevated LDH were IDH2 (n=19, 25.3%), RUNX1 (n=17, 23%), and DNMT3A (n=16, 21.6%). All patients (n=82, 100%) in the non-elevated LDH group received therapy after diagnosis. There was no difference in terms of treatment regimens used between the 2 groups. Moreover, no statistical difference in remission rates after one line of therapy was found between those groups where non-elevated LDH patients had a 65.9% remission rate compared to the 55.3% remission rate in patients with elevated LDH (p=0.098). Patients with elevated LDH had a shorter OS than patients with non-elevated LDH (9.5 vs. 26.4 months, p=0.0008). However, median OS was similar across the different groups of elevated LDH. Using univariate analysis in our cohort (n=381), age, HSCT, risk stratification, FLT3 mutation, and LDH elevation all had an impact on OS. However, when comparing those variables using multivariate analysis, age and FLT3 mutation lost their significance (p-value of 0.25 and 0.84, respectively).Complex karyotype and FLT3 mutations were more common in patients with elevated LDH. These patients tend to have higher WBC and peripheral blasts. Elevated LDH had a negative impact on patients' OS regardless of patients' risk classification.

Importance Treatment for cognitive dysfunction due to postacute sequelae of long COVID (ie, symptoms of fatigue, malaise, weakness, confusion that persist beyond 12 weeks after an initial COVID infection) remains a significant unmet need. Objective To test evidence-based rehabilitation strategies for improving cognitive symptoms in persons with long COVID. Design, Setting, and Participants This was a 5-arm, multicenter, randomized clinical trial of 3 remotely delivered interventions conducted between August 17, 2023, and June 10, 2024. The study took place at 22 trial sites and included the screening of individuals with cognitive long COVID. Interventions Participants were randomized to 1 of 5 arms: adaptive computerized cognitive training (BrainHQ [Posit Science]), cognitive-behavioral rehabilitation involving both group and individual counseling sessions (PASC-Cognitive Recovery [PASC-CoRE]) paired with BrainHQ, and transcranial direct current stimulation (tDCS) paired with BrainHQ. Two comparator arms were included as follows: unstructured computer puzzles and games (active comparator) and sham tDCS paired with BrainHQ. The interventions occurred 5 times per week over 10 weeks. Main Outcomes and Measures Cognitive and behavioral in-person assessments were performed at baseline, midintervention, at the end of intervention, and 3 months after the end of the intervention. The primary outcome measure was the modified Everyday Cognition Scale 2 (ECog2) completed at the end of the intervention compared to the baseline visit based on participant self-report looking back over the prior 7 days. Results A total of 378 individuals were screened, from which there were 328 participants (median [IQR] age, 48.0 [37.0-58.0] years; 241 female [73.5%]; race: 15 Asian [4.6%], 47 Black [14.3%], and 235 White [71.6%]; ethnicity: 52 Hispanic [15.9%]). None of the 3 active interventions demonstrated benefits on the modified ECog2 in the intention-to-treat population by the end of the intervention period. The adjusted differences in mean change were 0.0 (95% CI, −0.2 to 0.2) for BrainHQ vs active comparator, 0.1 (95% CI, −0.1 to 0.3) for PASC-CoRE + BrainHQ vs active comparator, 0.0 (95% CI, −0.2 to 0.2) for tDCS-active + BrainHQ vs tDCS-sham + BrainHQ, and 0.1 (95% CI, −0.1 to 0.3) for PASC-CoRE + BrainHQ vs BrainHQ alone. Secondary participant-reported outcomes and neuropsychological tests showed no differential benefits for any treatment arm. All 5 arms demonstrated some improvements over time on the modified ECog2 and on secondary outcomes. There were no serious adverse events attributable to the interventions. Conclusions and Relevance This phase 2 randomized clinical trial failed to demonstrate differential benefits for online cognitive training, a structured cognitive rehabilitation program, and tDCS for cognitive long COVID. Trial Registration ClinicalTrials.gov Identifier: NCT05965739 .

Background: Adults with congenital heart disease (CHD) face ongoing physical, emotional, and psychosocial challenges that impact long-term outcomes. Research is limited on how their health topic interests vary by levels of empowerment. The 15-item Gothenburg Empowerment Scale (GES) assesses CHD patient empowerment across five domains. Objective: Examine the association between patient empowerment levels and patient-prioritized health education topics among adults with CHD. Methods: This cross-sectional study included adults (≥18) with self-reported CHD enrolled in the Empower My Congenital Heart digital study. Participants completed the GES survey and responded to open-ended questions regarding information of interest to them in managing their healthcare. GES scores were divided into tertiles, and responses were grouped into patient-prioritized topics. Descriptive analysis examined associations between empowerment levels and topic preferences. Results: Of 292 eligible patients, mean age was 45.6 ± 14.7 years, 91.4% were Caucasian, and 66.4% were female. The median (25th, 75th) GES score was 62 (57, 68). The most frequently observed patient prioritized topic was CHD health knowledge (73%), followed by interest in building CHD community (52.7%), lifestyle management (23.6%), health care navigation (7.2%), research and representation (5.1%). Participants in the lower and middle GES tertiles more frequently expressed interest in foundational sub-topics such as understanding CHD and surgical history, finding ACHD specialists, exercise and nutrition. In contrast, participants in the highest GES tertile prioritized sub-topics related to aging with CHD, managing menopause, CHD research and legislative activities. Peer support was a common topic across all groups (Figure 1). Patient quotes were stratified by tertile and patient prioritized health topics and subtopics as summarized in table 1. Conclusion: Adults with CHD prioritized varied health education topics depending on their baseline empowerment levels. Those with lower GES scores prioritized foundational information and guidance, while those with higher scores prioritized community-oriented and research-related topics. These findings could help tailor CHD patient-centered education strategies based on individual empowerment profiles.

Background: Digital health offers a potential solution to support adults with congenital heart disease (CHD), filling the critical gap to help maintain recommended lifelong care with adult CHD specialists. However, its design and implementation require a rigorous scientific approach to make it scalable and usable for the target population. Objective: To pilot test the acceptability and feasibility of a digital health intervention to support lifelong healthcare for adults with CHD. Methods: Using a community-based participatory research and a behavioral theory-based approach, we developed and piloted a digital tool, Empower My Congenital Heart (EmpowerMyCH), within the web—and mobile-based Eureka Digital Research platform at UCSF. Intervention components within EmpowerMyCH include exhibits (expert and peer-developed learning modules on CHD-related topics such as finding specialists or navigating visits, tests, procedures, etc.), peer support, and a digital medical passport (Figure 1). Participants receive an exhibit with study measure surveys every two months, with a two-month completion window. Participant satisfaction with the digital tool is measured at six months using the Client Satisfaction Questionnaire-8 (CSQ-8), a validated survey with scores ranging from 8 to 32; higher scores indicate higher satisfaction with the digital tool. Results: Of the 519 participants recruited, 495 were eligible adults with CHD, 445 consented, and 6 withdrew. The median age was 43 (ranging from 20 to 85) years, and 30.1% were males. Survey completion rate was the highest at 88.7% during the first two months after enrollment and 53.5% at 8 months. Of the five exhibits delivered so far, over 87% of participants rated the exhibits to be helpful (Figure 2). Participants found the exhibits readable, easily accessible, motivational, useful, and educational (Figure 3). The median (25th, 75th) CSQ-8 score was 21 (18, 25) among 144 participants who completed the survey. Conclusions: EmpowerMyCH, the digital health tool, appears to be acceptable to most adults with CHD to support and educate them in navigating their healthcare. The tool and its contents are accessible, user-friendly, and responsive to the needs of the CHD community, resulting in high satisfaction rates. The feasibility rates and satisfaction scores are similar to or higher for EmpowerMyCH than those of prior digital health studies. Future hybrid intervention trials can demonstrate EmpowerMyCH‘s effectiveness.

Background: It is currently unknown whether patient engagement in adult congenital heart disease (CHD) care is influenced by social determinants of health (SDOH) such as race/ethnicity, education, and income. Adapting from the chronic care model, patient engagement, defined as the knowledge, skills, ability, and willingness to manage one’s health, can minimize lapses in care and improve CHD care outcomes. Methods: This cross-sectional study analyzes data from patients aged 18 and older with a self-reported diagnosis of CHD enrolled in a digital health research study called Empower My Congenital Heart. Patient engagement was measured using the Gothenburg Empowerment Scale (GES). We compared mean GES scores across demographic categories (race/ethnicity, education, and income), using independent samples t-tests or one-way ANOVA as appropriate. Additionally, we conducted a multivariate linear regression analysis to evaluate the impact of race/ethnicity, education, and income on GES scores, adjusting for age, gender, marital status, parental status, and employment status. Results: Of 323 adult CHD patients, the mean age was 45.6 ±15 years, 32.5% were males, 89.9% were non-Hispanic White, 29.7% had less than a Bachelor's degree, and 43.5% had less than $100,000 annual household income. The mean GES score was 61.8 ± 8, with significantly higher scores observed for non-Hispanic White identifying individuals (p=0.006) and those with a Bachelor's or higher level of education (p=0.005), while no difference across income levels (p = 0.394) (Figure 1). Linear regression analysis demonstrated that race and ethnicity remained significantly associated with GES scores (Table 1). Conclusions: Race/ethnicity and education level (in the bivariate analysis only), but not income, are the SDOH variables significantly associated with how empowered a CHD patient is in managing their health care. Future interventions that target enhancing patient engagement and self-management skills should take into consideration the influence of these demographic and social factors.

ABSTRACT Antimicrobial‐resistant bacteria, a growing worldwide concern, reduce the effectiveness of antibiotics against a wide range of microbial infections. Various bacterial species have quickly developed antibiotic resistance since the first mention of penicillin resistance in 1947. A rise in mortality, more extended hospital stays, more healthcare expenditures, and morbidity are all brought about by these bacteria that are resistant to antibiotics. To develop resistance, bacteria may undergo genetic changes, engage in horizontal gene transfer, produce β‐lactamase, activate efflux pumps, form biofilms, and alter their metabolism to become less susceptible to drugs. Environmental factors and sublethal antibiotic exposure exacerbate resistance, particularly in cases of persistent infections caused by biofilms. This tendency is prompted by the overuse of antibiotics in both human and veterinary medicine, as well as inadequate infection control measures and environmental pollution. This review presents an extensive survey of antimicrobial resistance across bacterial taxa, with a focus on the physiological and genetic processes underlying this phenomenon. It delves into the current therapeutic landscape and showcases cutting‐edge methods—such as artificial intelligence‐driven antibiotic discovery and resistance prediction—to inform the development of next‐generation antibiotics and containment systems.