bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prospective screening and proposed treatment algorithm for immune checkpoint inhibitor induced myositis in neoadjuvant-treated rectal cancer patients: data from the phase II CHINOREC trial
Authors: Zirnbauer R , Hametner S , Bergler-Klein J , Kuehrer I , Kulu A , Ammon D , Kabiljo J , Stift A , Schmid R , Laengle F , Machold K , Lambrechts D , Blueml S , Bergmann M , Laengle J 
Published: October 2024

Abstract

Background
Myositis is an infrequent (&lt;1%) but potentially life-threatening (case fatality rate 40-50%) immune-related adverse event (irAEs) of immune checkpoint inhibitors (ICI), such as ipilimumab (IPI) and nivolumab (NIVO). The true incidence is likely to be underestimated and may not be representative for curative neoadjuvant treatment approaches in gastrointestinal (GI) cancers, especially in combination with chemoradiotherapy (CRT). Currently, the summary of product characteristics (SmPC) does not suggest any pre-emptive screening or surveillance.

Methods
The CHINOREC study is an ongoing prospective, randomized, open-label, multicenter, phase II investigator-initiated trial (IIT). Patients with intermediate to locally advanced rectal cancer (LARC) receive either neoadjuvant CRT alone or in combination with a single dose of IPI and 3 cycles of NIVO, following surgical resection. Patients are monitored at baseline and throughout the whole study period for myotoxicity biomarkers, including cardiac troponin T (cTnT) and cardiac troponin I (cTnI).

Findings
From 06/2020 to 11/2023, 80 patients have been enrolled of whom 50 patients were randomized to the CRT+IPI/NIVO arm. Six patients (12%) developed biopsy-verified myositis. Myositis treatment was promptly implemented using a pragmatic step-up approach. Patients received glucocorticoids (GC) with concomitant intravenous immunoglobulin (IVIG). If myotoxicity biomarkers did not improve, patients received infliximab (INFLIXI) and/or plasma exchange (PLEX). Although all patients had strikingly elevated cTnT (median peak 284 ng/L, 95% CI 39-3097), cTnI levels remained largely normal, correlating with a negative cardiac magnetic resonance (CMR). All patients underwent successful tumor surgery without any major surgical complication. As of today, all patients' creatine kinase (CK) and myoglobin (MB) levels have normalized and they are tumor free without any major sequela.

Interpretation
Longitudinal biomarker screening (cTnT/cTnI) for ICI-induced myotoxicities is pivotal in curative neoadjuvant-treated cancer patients to initiate an early counter treatment in a holistic step-up approach, without compromising oncological principles.
Echocardiographic variables may improve baseline risk prediction of cancer therapy related cardiac dysfunction
Authors: Ruane L , Prasad S , Atherton J 
Published: October 2024

Abstract

Background
Baseline prediction of cancer therapy related cardiac dysfunction (CTRCD) in clinical practice is difficult, despite many known cancer and cardiovascular risk factors. Risk scores exist, including the HFA-ICOS score which is recommended by the 2022 European Society of Cardiology (ESC) Cardio-Oncology guidelines. Validation of such risk scores is required though, and identification of alternative risk factors that may improve risk prediction is needed.

Purpose
To assess the accuracy of the HFA-ICOS score for predicting CTRCD, and identify new risk factors with a focus on baseline echocardiography.

Methods
Echocardiograms and medical records were assessed for a cohort of breast cancer patients receiving trastuzumab or an anthracycline, who underwent serial echocardiographic monitoring. CTRCD was defined according to the 2022 ESC Cardio-Oncology guidelines. Baseline risk factors and echocardiography were compared between CTRCD and non-CTRCD groups, and the accuracy of the HFA-ICOS score in predicting CTRCD assessed.

Results
Data from 258 patients were analysed with CTRCD occurring in 23 (9%). 135 were low risk, 85 moderate-risk, 31 high-risk and 8 very high-risk according to the HFA-ICOS score with a trend of increasing rates of CTRCD with each risk category: 5%, 12%, 10%, 25%, respectively. The sensitivity and specificity of a combined moderate/high/very high-risk group was 70% and 54% (AUC 0.618, 95% CI 0.5-0.73). Only three individual baseline variables were associated with CTRCD in this cohort; ejection fraction 50-54%, (18% vs 2%, p=0.0027), borderline/abnormal average global longitudinal strain &lt;-18, (43% vs 19%, p=0.04) and combination anthracycline plus trastuzumab, (45% vs 22%, p=0.0392). Left atrial volume index &gt;34mL/m² was also higher in the CTRCD group (38% vs 23%) although not statistically significant. A simplified risk score using only these variables yielded a sensitivity and specificity of 74% and 53%, respectively (AUC 0.633, 95% CI 0.52-0.75).

Conclusion
Baseline prediction of CTRCD remains difficult in clinical practice. Although HFA-ICOS risk categories correlate with CTRCD diagnosis, the overall sensitivity is only moderate. Echocardiographic variables may further enhance risk prediction to enable development of targeted monitoring strategies.HFA-ICOS risk score categoriesROC curves
Cardioprotective role of statins in breast cancer patients treated with anthracyclines and/or trastuzumab: a systematic review and meta-analysis
Authors: Lingamsetty S S P , Kritya M , Huang W , Fatima S R , Gewehr D M , Doma M , Pastrana S H , Hemdanieh M , Naji Z , Kuhar K , Martignoni F 
Published: October 2024

Abstract

Background
Statins may have cardioprotective effects in patients undergoing cardiotoxic chemotherapy regimens. Yet, their role in mitigating anthracycline and/or trastuzumab-induced cardiotoxicity in patients with breast cancer remains unclear.

Purpose
To perform a systematic review and meta-analysis to evaluate the efficacy of statins in mitigating anthracycline and/or trastuzumab-induced cardiotoxicity among patients with breast cancer.

Methods
We systematically searched PubMed, Embase, and Cochrane databases until January 2024 for studies comparing the efficacy of statin therapy versus no statin therapy in breast cancer patients receiving either anthracyclines, trastuzumab, or both. Cardiotoxicity was defined as per the definition of each individual study. A random-effects model was used to assess pooled risk ratios (RR) and mean differences (MD) with corresponding 95% confidence intervals. Statistical analyses were performed using Review Manager version 5.4.1.

Results
We included five studies, of which two were randomised trials. The pooled population comprised 1,839 anthracyclines and/or trastuzumab-treated patients with breast cancer, of whom 864 (47%) received statin therapy. In the pooled analyses, cardiotoxicity was significantly lower in the statin therapy group as compared with the no statin therapy group (RR 0.45; 95% CI 0.27 to 0.72; p=0.001; Figure 1A), additionally statin therapy was associated with a significantly lower reduction in left ventricular ejection fraction as compared with no statin therapy (MD 4.11%; 95% CI 2.68 to 5.53; p&lt;0.00001; Figure 1B).

Conclusion
In this meta-analysis, statin therapy in anthracyclines and/or trastuzumab-treated patients with breast cancer was associated with lower cardiotoxicity and decline in left ventricular ejection fraction.
SLC4A3 anion exchanger mutations associated to sudden death : short or long QT syndrome?
Authors: Benbekhti S B , Maury P M , Placide L P , Delsarte L D , Massin F M , Granier M G , Probst V P , Pasquie J L P 
Published: October 2024

Abstract

Introduction
SLC4A3 gene codes for an (Cl-/HCO3-) exchanger present on the surface of cardiomyocytes (AE3 channel) is involved in maintaining the physiological acid-base gradient of the cardiomyocyte at rest. Loss of function of the SLC4A3 gene leading to an increase in intracellular pH has. been reported to be responsible for short QT syndrome (SQT).

Methods
The aim of our study was to characterize the genotype-phenotype relationships of SLC4A3 mutations identified in the French databases (Paris, Nantes and Lyon) in patients with sudden death. Through systematic exome sequencing we identified 3 new SLC4A3 variants in 3 families with a history of sudden death in two universitary hospitals.

Results
Family 1. The c.3209G&gt;C variant (p.Gly1070Ala) in the SLC4A3 gene was identified in a 7-yo boy with VF at sleep but admitted in encephalic death. EKG showed short QT (QTc 280ms). Clinical examination, blood tests, TTE and autopsy were normal. There was no family history of sudden death. His mother had EKG evidence of SQT and was carrier the SLC4A3 mutation. She was implanted with an ICD. His two older brothers and the rest of the family had no mutation or pathological ECG and were asymptomatic.
Family 2. The c.1027C&gt;T (p.Arg343Cys) mutation in the SLC4A3 gene was identified in a 29-year-old man who presented with sudden death at sleep (VF). Clinical examination, blood tests, TTE and autopsy were normal. A maternal uncle died suddenly while sleeping. His two brothers (30 and 27 yo) are both carriers of the SLC4A3 mutation and exhibit SQT (QTc 320 and 330 ms respectively). TEE, Holter monitoring and stress test were normal in both. Both brothers were treated with hydroquinidine. Over a 2-year follow-up they had no symptom nor AF.
Family 3. The c.1022C&gt;G (p.Thr341Arg) mutation was identified in the SLC4A3 gene in a 54-yoman who presented with VF during shower but admitted in encephalic death. There was no family history of sudden death. Clinical examination, blood tests and echocardiography as well as coronary angiogram were normal. The initial ECG showed a prolonged QT interval (QTc 520 ms). QTc decreased to 480 ms in the 48 following hours. His parents and his sister as well as his 18 yo daughter have normal QTc values. We are awaiting the genetic results.

Conclusion
Loss-of-activity-mutation in the cardiac chloride-bicarbonate exchanger AE3 has been recently reported to cause short QT syndrome but it seems that in rare cases it may also be responsible for LQTS. Further patients are needed to confirm these data. In order to understand the underlying electrophysiological mechanisms, we plan to characterize the cellular impact of these new mutations through IPS.
Risk assessment using DEVI and CARPREG -1 score to predict maternal adverse cardiac cvents in pregnancies with valvular heart disease: external validation study from MPAC registry
Authors: Gnanaraj J P , Anne Princy S , Anju S , Keepanasseril A 
Published: October 2024

Abstract

Background
Even though many risk assessment tools in pregnant women with valvular heart disease (VHD) are available, validation studies are few that assess their performance in diverse settings, which is needed prior to the application of routine clinical practice.

Objectives
To validate and establish the clinical utility of two risk stratification tools – DEVI (VHD-specific tool) and CARPREG-I in predicting adverse cardiac events in pregnant patients with VHD.

Methods
This cohort study involved consecutive pregnancies complicated with VHD enrolled in the prospective MPAC registry from July 2016 to December 2019(1). The ability to discriminate those with and without adverse cardiac outcomes was assessed using the area under the curve for both the DEVI and CARPREG-1 scores. Performance was assessed through discrimination and calibration characteristics. Clinical utility was evaluated with Decision Curve Analysis.
Results Among 1029 pregnancies complicated with heart disease in the MPAC registry cohort, 604(52.3%) with valvular heart disease were included in this analysis. One or more composite adverse cardiac events occurred in 70 (11.6%) pregnancies during antenatal or the early postpartum period. Mitral regurgitation was the most common lesion (67.7%). In assessing the pregnancy outcomes, those who continued past 20 weeks were included, with the majority (92.0%) delivered at term, and the cesarean rates were 33.6% (n=203). The most common adverse event was heart failure (n=32, 5.3%), most of which (68.6%) occurred in the postnatal period. There were 11 maternal deaths (1.8%) during the study period, six among those with mechanical heart valves (four prosthetic valve thrombosis), two among those with severe mitral stenosis and pulmonary hypertension and two with severe mitral regurgitation and infective endocarditis.
The area under the receiver operating characteristic curve (AUC) was 0.766, with 95% confidence intervals (CI) 0.703- 0.828 for DEVI and 0.703 (95%CI 0.644- 0.763) for CARPREG-I models. Calibration plots suggested that the DEVI score overestimates risk at higher probabilities, whereas the CARPREG-I score underestimates the risk at most probabilities. Decision curve analysis demonstrated that both models were useful across predicted probability thresholds between 10% and 60%.

Conclusion
In this external validation study in pregnant women with primary rheumatic VHD, DEVI and CARPREG-I scores showed good discrimination ability and clinical utility across various probabilities. Both can be used to classify those who develop adverse cardiac outcomes during pregnancy and childbirth. However, both models need recalibration to improve the agreement between the predicted and observed events prior to routine application in diverse clinical settings.Figure 1.a and b ROC and Decision Curves
Severity of pulmonary hypertension and pregnancy outcomes: newer insights from the M-PAC registry
Authors: Gnanaraj J P , Anne Princy S , Anju Surendran S , Meena Suresh T S , Kalaivani K , Kanmani K , Nandakumaran M , Ashok Viktor A V , Rani D R , Prathap Kumar G , Rajasekar Ramesh D , Elavarasi E , Elangovan C , Nageswaran P M , Arul A S 
Published: October 2024

Abstract

Background
Pregnancy outcomes in women with pulmonary hypertension remain suboptimal. Pregnant women with pulmonary hypertension (PH) are placed in the modified WHO category IV, regardless of the severity or etiology of PH. Earlier studies have indicated that pregnancy outcomes may differ based on the etiology, with more favourable outcomes observed with PH related to left to right shunts. However, it is possible that the pregnancy outcomes may vary based on the severity of PH also.

Purpose
To analyse pregnancy outcomes in women with PH and investigate differences based on disease severity.

Methods
M-PAC Registry, is a single center prospective study of pregnancies in women with heart diseases, conducted between July 2016 and December 2019 in a low-and middle-income country from South Asia, whose methodology and outcomes have been published(1). The current study analysed pregnancies with PH enrolled in the M-PAC registry. The tricuspid regurgitation velocity obtained during transthoracic echocardiography, was used to estimate right ventricular systolic pressure (RVSP). Based on the estimated RVSP, PH was classified into three groups; mild (36-45 mm of Hg), moderate (46-64 mm of Hg) and severe (≥ 65 mm of Hg). The differences in the maternal and foetal outcomes among the groups were analysed.

Results
Of the 1029 pregnancies complicated by heart disease enrolled in the M-PAC registry, 352(34.2%)had PH. Among these 352 pregnancies, 186(52.8%) had mild, 73 (20.7%) had moderate and 93 (26.5%) had severe PH.
Adverse maternal cardiac events occurred in 77 pregnancies (21.8%), with heart failure in 53(15.1%) and mortality in 10(2.8%). The composite adverse foetal event rate was 38.6%, foetal loss at 9.7%, low birth weight at 28.9%, and preterm labour at 7.1%. The mean (±standard deviation) RVSP was higher in pregnancies with adverse maternal outcome (58.81±16.9 vs 51.16±15.9; P &lt; 0.001) or adverse foetal outcome (58.10±17.3 vs 49.52±14.9; P &lt; 0.001)compared to those without.
When comparing the three groups, pregnancies with mild PH exhibited significantly lower rates of adverse maternal and fetal events compared to those with severe and moderate PH (Fig-1 and Table-1). Mild PH was associated with outcomes similar to those without PH in the M-PAC registry.

Conclusion
The severity of PH significantly correlated with the adverse pregnancy outcomes. Women with mild PH tend to experience pregnancy outcomes comparable to those without PH, suggesting that pregnancy should not be deemed contraindicated in this subgroup. Therefore, re-evaluation of the placement of PH within the modified World Health Organization (mWHO) classification is warranted, considering the severity of PH.Figure 1:Pregnancy Outcomes & PH SeverityTable-1 PH Severity & Pregnacny Outcomes
The relationship between coronary flow reserve and the TyG index in patients with gestational diabetes mellitus
Authors: Bugday I , Ozyildirim S , Barman H A , Dogan O , Aydin I , Ozkan F , Abbasov Y , Ersanli M K , Dogan S M 
Published: October 2024

Abstract

Gestational diabetes mellitus (GDM) is a prevalent metabolic disorder characterized by glucose intolerance during pregnancy. The triglyceride glucose (TyG) index, a marker of insulin resistance, and coronary flow reserve (CFR), a measure of coronary microvascular function, are emerging as potential indicators of cardiovascular risk.
This study aims to investigate the association between CFR and the TyG index in GDM patients.
This cross-sectional study of 87 GDM patients and 36 healthy controls was conducted. The participants underwent clinical assessments, blood tests, and echocardiographic evaluations. The TyG index was calculated as ln(triglycerides × fasting glucose/2). CFR was measured using Doppler echocardiography during rest and hyperemia induced by dipyridamole.
The study included 87 individuals in the GDM group and 36 individuals in the control group. There was no significant difference in age between the two groups (34.1 ± 5.3 years for GDM vs. 33.1 ± 4.9 years for the control, p = 0.364). The TyG index was significantly higher in the GDM group compared to the controls (p &lt; 0.001) and CFR was lower in the GDM group (p &lt; 0.001) as shown in Figure 1a and 1b. A negative and significant correlation between the TyG index and CFR was observed, which was demonstrated in Figure 2 (r = −0.624, p &lt; 0.001). Linear regression revealed the TyG index as an independent predictor of reduced CFR.
The study findings reveal a significant association between the TyG index and CFR in GDM patients, suggesting their potential role in assessing cardiovascular risk.TyG index and CFR of the groupsTyG and CFR correlation analysis
Characterization of left atrial function during cardiac (reverse) remodeling induced by pregnancy
Authors: Ferreira A F , Anjos S , Azevedo M J , Morais J , Saraiva F A , Diaz S O , Sousa C , Machado A P , Leite-Moreira A , Sampaio-Maia B , Ramalho C , Barros A S , Falcao-Pires I 
Published: October 2024

Abstract

Introduction
The hemodynamic overload in pregnancy leads to cardiovascular remodeling, characterized by enlargement of left atrial (LA) and ventricular (LV) volumes associated with impaired LV relaxation, maintaining preserved systolic function. These changes are reversible during postpartum. Few scientific evidence has been published about LA function yet.

Purpose
To assess the changes in LA function through two-dimensional speckle tracking echocardiography analysis during pregnancy and its recovery up to 1 year after delivery and to determine potential predictors of its progression.

Methods
This prospective cohort study included volunteer pregnant women (healthy, obese and/or hypertensive and/or with gestational diabetes) recruited in two tertiary centers between 2019 and 2021. Women were evaluated by transthoracic echocardiography at the 1st trimester [1T, 10-15 weeks, baseline], 3rd trimester [3T, 30-35 weeks, peak of cardiac remodeling] of pregnancy as well as at the 1st, 6th and 12th month after delivery (during RR). Generalized linear mixed-effects models evaluated the extent of RR, including the variation of left atrial strain and its potential predictors.

Results
We included 130 pregnant women with a median age of 33 [30,36] years, 39,2% multiparas. Fifty-four (41.5%) were diagnosed with at least one cardiovascular risk factor. A significant enlargement of LA volume (24 [22, 28]mL/m2 to 29 [25, 33]mL/m2, p&lt;0.001) associated with the increase of E/e’ (5.85 [5.08, 6.36] to 6.70 [5.67, 7.82], p&lt;0.001) was observed from 1T to 3T, both recovering as soon as 1 month after delivery (LA volume: 29 [25, 33]mL/m2 to 24 [20, 27] mL/m2, p&lt;0.001; E/e’: 6.70 [5.67, 7.82] to 5.70 [4.82, 6.47], p&lt;0.001). Regarding LA function, a significant reduction of LA strain was verified from 1T to 3T (35 [31, 41]% to 31 [29, 36]%, p&lt;0.001), recovering 6 months postpartum (31 [29, 36]% to 33 [30, 38]%, p=0.035). Systemic vascular resistance seemed to be an independent predictor of lower LA strain (-3.83 [-6.40, -1.25], p=0.004). The presence of cardiovascular risk factors (-0.80 [-2.28, 0.68], p=0.287), smoking habits (-1.26 [-2.82, 0.30], p=0.112), parity (-0.33 [-1.93, 1.27], p=0.684) and age (-0.11 [-0.29, 0.08], p=0.257) showed a non-significant impact in LA strain.

Conclusion
Despite the recovery in diastolic function and LA volume 1 month after delivery, the LA function only significantly improved 6 months later. Systemic vascular resistance was revealed as an independent predictor of LA strain.
The effect of HIV seropositivity on inpatient outcomes in atrial tachyarrhythmias: a US population analysis
Authors: Brown D , Dixon B , Cummings S , Simpson T , Henry D , Folkes J , Piplani S , Gallippi V , Sedaghati M , Radulovic M 
Published: October 2024

Abstract

Background
With the advent of antiretroviral therapy, the life expectancy of persons living with HIV(PLHIV) has been significantly prolonged and we are now seeing this group increasingly affected by chronic conditions. Atrial fibrillation is the most common sustained tachyarrhythmias in adults and commonly coexists with atrial flutter. HIV-1 especially has been shown to possess a specific cardiac tropism in which chronic immune activation and inflammation may lead to cytotoxicity and death of cardiac myocytes. It has also been associated with left atrial enlargement, which may increase arrhythmia generation and propagation. The effect of HIV on outcomes in atrial tachyarrhythmias have been poorly studied, so we therefore wanted to explore this influence on in-patient outcomes.

Purpose
To assess the effect of HIV seropositivity on inhospital outcomes of patients admitted with atrial fibrillation/flutter (AF)

Method
The study uses data from the HCUP-NIS database, which includes billing information from hospitals across the US. The study population included patients admitted with a principal diagnosis of atrial fibrillation or atrial flutter in 2020. Patients with HIV positivity were identified using ICD-10 codes. Multivariate regression was used to analyze outcomes while adjusting for confounders. They were classified into two groups: AF-only (AF-O) and AF with HIV (AF-H).

Results
A total of 400,715 patients were admitted with a primary diagnosis of atrial fibrillation/flutter in 2020, 1175 were PLHIV. Patients in the AF-H group were more likely to be younger, non-Caucasian, tobacco smokers, have lower median income, be uninsured, have HFrEF and CKD. They however had lower rates of HFpEF than persons in the AF-O group. After adjusting for hospital level confounders, the in-hospital mortality rate was similar between the two groups (aOR 0.46 95% CI 0.05-3.98, p=0.48). The rates of ischemic stroke/systemic embolization, major bleeding, in hospital respiratory failure, length of stay and total hospital charges were also not significantly different

Conclusion
The study suggests that AF patients with HIV have similar in-hospital mortality rates as patients without. There are significant differences in the economic and ethnic makeup of the two groups but these did not significantly influence the outcomes of interest. Larger cohorts will be needed to confirm these findings definitively, especially as more persons with HIV continue surviving past the sixth decade of life.