Accuracy and consistency of online large language model-based artificial intelligence chat platforms in answering patients' questions about heart failure.

BACKGROUND: Heart failure (HF) is a prevalent condition associated with significant morbidity. Patients may have questions that they feel embarrassed to ask or will face delays awaiting responses from their healthcare providers which may impact their health behavior. We aimed to investigate the potential of large language model (LLM) based artificial intelligence (AI) chat platforms in complementing the delivery of patient-centered care. METHODS: Using online patient forums and physician experience, we created 30 questions related to diagnosis, management and prognosis of HF. The questions were posed to two LLM-based AI chat platforms (OpenAI's ChatGPT-3.5 and Google's Bard). Each set of answers was evaluated by two HF experts, independently and blinded to each other, for accuracy (adequacy of content) and consistency of content. RESULTS: ChatGPT provided mostly appropriate answers (27/30, 90%) and showed a high degree of consistency (93%). Bard provided a similar content in its answers and thus was evaluated only for adequacy (23/30, 77%). The two HF experts' grades were concordant in 83% and 67% of the questions for ChatGPT and Bard, respectively. CONCLUSION: LLM-based AI chat platforms demonstrate potential in improving HF education and empowering patients, however, these platforms currently suffer from issues related to factual errors and difficulty with more contemporary recommendations. This inaccurate information may pose serious and life-threatening implications for patients that should be considered and addressed in future research.

Right Ventricular Contractility and Pulmonary Arterial Coupling After Less Invasive Left Ventricular Assist Device Implantation.

Right ventricular failure contributes significantly to morbidity and mortality after left ventricular assist device implantation. Recent data suggest a less invasive strategy (LIS) via thoracotomy may be associated with less right ventricular failure than conventional median sternotomy (CMS). However, the impact of these approaches on load-independent right ventricular (RV) contractility and RV-pulmonary arterial (RV-PA) coupling remains uncertain. We hypothesized that the LIS approach would be associated with preserved RV contractility and improved RV-PA coupling compared with CMS. We performed a retrospective study of patients who underwent durable, centrifugal left ventricular assist device implantation and had paired hemodynamic assessments before and after implantation. RV contractility (end-systolic elastance [Ees]), RV afterload (pulmonary effective arterial elastance [Ea]), and RV-PA coupling (Ees/Ea) were determined using digitized RV pressure waveforms. Forty-two CMS and 21 LIS patients were identified. Preimplant measures of Ees, Ea, and Ees/Ea were similar between groups. After implantation, Ees declined significantly in the CMS group (0.60-0.40, p = 0.008) but not in the LIS group (0.67-0.58, p = 0.28). Coupling (Ees/Ea) was unchanged in CMS group (0.54-0.59, p = 0.80) but improved significantly in the LIS group (0.58-0.71, p = 0.008). LIS implantation techniques may better preserve RV contractility and improve RV-PA coupling compared with CMS.

4'-Ethynyl-2'-Deoxycytidine (EdC) Preferentially Targets Lymphoma and Leukemia Subtypes by Inducing Replicative Stress.

Anticancer nucleosides are effective against solid tumors and hematological malignancies, but typically are prone to nucleoside metabolism resistance mechanisms. Using a nucleoside-specific multiplexed high-throughput screening approach, we discovered 4'-ethynyl-2'-deoxycytidine (EdC) as a third-generation anticancer nucleoside prodrug with preferential activity against diffuse large B-cell lymphoma (DLBCL) and acute lymphoblastic leukemia (ALL). EdC requires deoxycytidine kinase (DCK) phosphorylation for its activity and induced replication fork arrest and accumulation of cells in S-phase, indicating it acts as a chain terminator. A 2.1Å co-crystal structure of DCK bound to EdC and UDP reveals how the rigid 4'-alkyne of EdC fits within the active site of DCK. Remarkably, EdC was resistant to cytidine deamination and SAMHD1 metabolism mechanisms and exhibited higher potency against ALL compared to FDA approved nelarabine. Finally, EdC was highly effective against DLBCL tumors and B-ALL in vivo. These data characterize EdC as a pre-clinical nucleoside prodrug candidate for DLBCL and ALL.

Cardio-Obstetric Shock: Mechanical Circulatory Support as a Bridge to Pregnancy Viability.

Cardiogenic shock in pregnancy is rare but is associated with significant morbidity and mortality. Timely recognition with multidisciplinary management is necessary for optimal maternal and fetal outcomes. Here we present a case of cardiogenic shock in the antepartum period managed with mechanical circulatory support as a bridge to pregnancy viability.

Social and Emotional Learning and Ninth-Grade Students' Academic Achievement.

A central component of adolescents' social and emotional learning (SEL) consists of their ability to foster positive relationship skills through connectedness with their school community. This study focuses on the assessment of student's SEL competencies in relation to their socio-demographic characteristics, formal and informal socialization behaviors, and academic outcomes in both public and private schools. The research is based on the secondary analysis of large-scale nationally representative data from the High School Longitudinal Study of 2009 (HSLS:2009) and focuses on ninth graders experiencing the transition to secondary education. Guided by both SEL and school climate frameworks, we identified survey items that describe students' feelings of acceptance, pride, and support in their grade nine learning environment as indicators of perceptions of school climate and builders of SEL skills and used multivariate statistical analysis to examine how SEL skills and behavioral socialization affect school achievement. Study findings should inform school practitioners in developing academic and socio-cultural programs that incorporate SEL skills development.

Qualitative interviews to understand methods and systems used to collect ethnicity information in health administrative data sources in England.

Background: This article is one of a series aiming to inform analytical methods to improve comparability of estimates of ethnic health disparities based on different sources. This article explores the quality of ethnicity data and identifies potential sources of bias when ethnicity information is collected in three key NHS data sources. Future research can build on these findings to explore analytical methods to mitigate biases. Methods: Thematic analysis of semi-structured qualitative interviews to explore potential sources of error and bias in the process of collecting ethnicity information across three NHS data sources: General Practice Extraction Service (GPES) Data for Pandemic Planning and Research (GDPPR), Hospital Episode Statistics (HES) and Improving Access to Psychological Therapies (IAPT). The study included feedback from 22 experts working on different aspects of health admin data collection for England (including staff from NHS Digital, IT system suppliers and relevant healthcare service providers). Results: Potential sources of error and bias were identified across data collection, data processing and quality assurance processes. Similar issues were identified for all three sources. Our analysis revealed three main themes which can result in bias and inaccuracies in ethnicity data recorded: data infrastructure challenges, human challenges, and institutional challenges. Conclusions: Findings highlighted that analysts using health admin data should be aware of the main sources of potential error and bias in health admin data, and be mindful that the main sources of error identified are more likely to affect the ethnicity data for ethnic minority groups. Where possible, analysts should describe and seek to account for this bias in their research.

Impact of Donor Hemodynamics on Recipient Survival in Heart Transplantation.

BACKGROUND: Heart transplantation is the gold-standard therapy for end-stage heart failure, but rates of donor-heart use remain low due to various factors that are often not evidence based. The impact of donor hemodynamics obtained via right-heart catheterization on recipient survival remains unclear. METHODS: The United Network for Organ Sharing registry was used to identify donors and recipients from September 1999-December 2019. Donor hemodynamics data were obtained and analyzed using univariate and multivariable logistical regression, with the primary endpoints being 1- and 5-year post-transplant survival. RESULTS: Of the 85,333 donors who consented to heart transplantation during the study period, 6573 (7.7%) underwent right-heart catheterization, of whom 5531 eventually underwent procurement and transplantation. Donors were more likely to undergo right-heart catheterization if they had high-risk criteria. Recipients who had donor hemodynamic assessment had 1- and 5-year survival rates similar to those without donor hemodynamic assessment (87% vs 86%, 1 year). Abnormal hemodynamics were common in donor hearts but did not impact recipient survival rates, even when risk-adjusted in multivariable analysis. CONCLUSIONS: Donors with abnormal hemodynamics may represent an opportunity to expand the pool of viable donor hearts.

DNA polymerase θ protects leukemia cells from metabolically induced DNA damage.

Leukemia cells accumulate DNA damage, but altered DNA repair mechanisms protect them from apoptosis. We showed here that formaldehyde generated by serine/1-carbon cycle metabolism contributed to the accumulation of toxic DNA-protein crosslinks (DPCs) in leukemia cells, especially in driver clones harboring oncogenic tyrosine kinases (OTKs: FLT3(internal tandem duplication [ITD]), JAK2(V617F), BCR-ABL1). To counteract this effect, OTKs enhanced the expression of DNA polymerase theta (POLθ) via ERK1/2 serine/threonine kinase-dependent inhibition of c-CBL E3 ligase-mediated ubiquitination of POLθ and its proteasomal degradation. Overexpression of POLθ in OTK-positive cells resulted in the efficient repair of DPC-containing DNA double-strand breaks by POLθ-mediated end-joining. The transforming activities of OTKs and other leukemia-inducing oncogenes, especially of those causing the inhibition of BRCA1/2-mediated homologous recombination with and without concomitant inhibition of DNA-PK-dependent nonhomologous end-joining, was abrogated in Polq-/- murine bone marrow cells. Genetic and pharmacological targeting of POLθ polymerase and helicase activities revealed that both activities are promising targets in leukemia cells. Moreover, OTK inhibitors or DPC-inducing drug etoposide enhanced the antileukemia effect of POLθ inhibitor in vitro and in vivo. In conclusion, we demonstrated that POLθ plays an essential role in protecting leukemia cells from metabolically induced toxic DNA lesions triggered by formaldehyde, and it can be targeted to achieve a therapeutic effect.

Outcomes in Patients With LVADs Undergoing Simultaneous Heart-Kidney Transplantation.

BACKGROUND: Multiple studies have shown better outcomes for simultaneous heart-kidney transplant (sHKT) than for isolated orthotopic heart transplant (iOHT) in recipients with chronic kidney disease (CKD). However, outcomes in patients supported by durable left ventricular assist devices (LVADs) have not been well studied. METHODS: Patients with durable LVADs and stage 3 or higher CKD (eGFR < 60 mL/min/1.73 m2) undergoing iOHT or sHKT between 2008 and 2020 were identified from the United Network for Organ Sharing registry. A Kaplan-Meier survival analysis with associated log-rank test was conducted to compare post-transplant survival rates. Multivariable modeling was used to identify risk-adjusted predictors of 1 year post-transplant mortality. RESULTS: We identified 4375 patients; 366 underwent sHKT, and 4009 underwent iOHT. The frequency of sHKT increased during the study period. The 1-year post-transplant survival rate was worse in patients after sHKT than in patients after iOHT (80.3% vs 88.3%; P < 0.001) and persisted up to 5 years post-transplant (P = 0.001). sHKT recipients were more likely to require dialysis after transplantation and had longer hospital lengths of stay (P < 0.001). Multivariable analysis showed that sHKT remained an independent risk factor for mortality at 1 year (OR 1.58; P = 0.002). CONCLUSIONS: sHKT is becoming more common in patients with durable LVADs. Compared with iOHT, patients with sHKTs have worse short- and long-term survival rates and are more likely to require post-transplant dialysis.

End-stage renal disease patients undergoing angioplasty and bypass for critical limb ischemia have worse outcomes compared to non-ESRD patients: Systematic review and meta-analysis.

BACKGROUND: End-stage renal disease (ESRD) is associated with increased morbidity and mortality following lower extremity amputation for critical limb ischemia (CLI). Angioplasty and bypass are used in ESRD patients with CLI; however, the treatment of choice remains controversial. We compared the long-term outcomes in patients with CLI undergoing angioplasty or bypass to evaluate the differences between patients with ESRD and those without ESRD. METHODS: Established databases were searched for observational studies comparing outcomes following bypass or angioplasty for CLI in patients with ESRD to those in non-ESRD patients. End points included survival, limb salvage, amputation-free survival (AFS), and primary and secondary patency at 1-year post-procedure. Pooled odds ratios (OR) with 95% confidence intervals (CI) were calculated using a random effect model. RESULTS: We included 20 studies with a total of 24,851 patients. ESRD patients compared to non-ESRD patients with CLI had significantly lower survival post-angioplasty (OR 0.51, 95% CI 0.36-0.72, p < .001) and post-bypass (OR 0.26, 95% CI 0.15-0.45, p < .001). ESRD patients had lower rates of limb salvage post-bypass (OR 0.33, 95% CI 0.21-0.53, p < .001) and post-angioplasty (OR 0.54, 95% CI 0.41-0.70, p < .001). AFS was significantly lower in ESRD patients compared to non-ESRD patients following angioplasty (OR 0.48, 95% CI 0.32-0.71, p < .001) and bypass (OR 0.28, 95% CI 0.16-0.47, p < .001) despite no significant differences in primary patency. ESRD patients had overall worse secondary patency post-angioplasty and/or bypass (OR 0.54, 95% CI 0.32-0.94, p = .03) compared to non-ESRD patients. A meta-analysis of four studies directly comparing survival in ESRD patients with CLI based on whether they underwent angioplasty or bypass showed no difference (OR 0.93, 95% CI 0.64-1.35, p = .69). CONCLUSION: ESRD patients have worse survival, limb salvage, and AFS outcomes following angioplasty and bypass for CLI compared to non-ESRD patients. Large randomized controlled trials comparing these two modalities of treatment in this patient population are needed for further clarity.

Outcomes of cardiac resynchronisation therapy in patients with heart failure with atrial fibrillation: a systematic review and meta-analysis of observational studies.

Background: Cardiac resynchronisation therapy (CRT) is beneficial in selected patients with heart failure (HF) in normal sinus rhythm (NSR). We sought to evaluate the impact of CRT with or without atrioventricular junction (AVJ) ablation in patients with HF with concomitant atrial fibrillation (AF). Methods and results: Literature was searched (inception through 30 August 2017) for observational studies that reported outcomes in patients with HF with CRT and AF that reported all-cause and cardiovascular mortality. Thirty-one studies with 83, 571 patients were included. CRT did not decrease mortality compared with internal cardioverter defibrillator or medical therapy alone in patients with HF and AF with indications for CRT (OR: 0.851, 95% CI 0.616 to 1.176, p=0.328, I2=86.954). CRT-AF patients had significantly higher all-cause and cardiovascular mortality than CRT-NSR patients ([OR: 1.472, 95% CI 1.301 to 1.664, p=0.000] and [OR: 1.857, 95% CI 1.350 to 2.554, p=0.000] respectively). Change in left ventricular ejection fraction was not different between CRT patients with and without AF (p=0.705). AVJ ablation, however, improved all-cause mortality in CRT-AF patients when compared with CRT-AF patients without AVJ ablation (OR: 0.485, 95% CI 0.247 to 0.952, p=0.035). With AVJ ablation, there was no difference in all-cause mortality in CRT-AF patients compared with CRT-NSR patients (OR: 1.245, 95% CI 0.914 to 1.696, p=0.165). Conclusion: The results of our meta-analysis suggest that AF was associated with decreased CRT benefits in patients with HF. CRT, however, benefits patients with AF with AVJ ablation.

Long term outcomes of new generation drug eluting stents versus coronary artery bypass grafting for multivessel and/or left main coronary artery disease. A Bayesian network meta-analysis of randomized controlled trials.

BACKGROUND: Most data guiding revascularization of multivessel disease (MVD) and/or left main disease (LMD) favor coronary artery bypass grafting (CABG) over percutaneous coronary intervention (PCI). However, those data are based on trials comparing CABG to bare metal stents (BMS) or old generation drug eluting stents (OG-DES). Hence, it is essential to outcomes of CABG to those of new generation drug eluting stents (NG-DES). METHODS: We searched PUBMED and Cochrane database for trials evaluating revascularization of MVD and/or LMD with CABG and/or PCI. A Bayesian network meta-analysis was performed to calculate odds ratios (OR) and 95% credible intervals (CrI). Primary outcome was major adverse cardiovascular events (MACE) at 3-5 years. Secondary outcomes were mortality, cerebrovascular accidents (CVA), myocardial infarction (MI) and repeat revascularization. RESULTS: We included 10 trials with a total of 9287 patients. CABG was associated with lower MACE when compared to BMS or OG-DES. However, MACE was not significantly different between CABG and NG-DES (OR 0.79, CrI 0.45-1.40). Moreover, there were no significant differences between CABG and NG-DES in mortality (OR 0.78, CrI 0.45-1.37), CVA (OR 0.93 CrI 0.35-2.2) or MI (OR 0.6, CrI 0.17-2.0). On the other hand, CABG was associated with lower repeat revascularization (OR 0.55, CrI 0.36-0.84). CONCLUSIONS: Our study suggests that NG-DES is an acceptable alternative to CABG in patients with MVD and/or LMD. However, repeat revascularization remains to be lower with CABG than with PCI.