Baseline Values Research Articles

Does HFpEF represent a risk factor and a marker of cardiotoxicity in patients undergoing cancer treatment?

Abstract Background The prevalence of heart failure with preserved ejection fraction (HFpEF) increases with the aging of our population and shares risk factors with cancer. Furthermore, HFpEF conveys a worse prognosis if it remains unrecognized and untreated. However, it is not considered as a surrogate marker in the baseline risk stratificatoin of patients that will undergo potentially cardiotoxic cancer treatments. Moreover, the definition of cardiotoxicity focuses mainly on systolic dysfunction, based on left ventricular ejection fraction and global longitudinal strain changes. Data on the prevalence of new-onset HFpEF during cancer treatment are limited. Purpose We evaluated the prevalence of HFpEF in cancer patients followed in our cardio-oncology clinic, with new cancer therapy-related cardiovascular toxicity (CTR-CVT) events in patients with known HFpEF prior to cancer therapy. We also assessed the prevalence of patients diagnosed with HFpEF while undergoing cancer therapy. Methods A total of 630 cancer patients referred for either baseline evaluation, on-treatment surveillance, long-term follow-up or new complaints suspect for cardiovascular disease were included in this real-world observational study, with a mean follow-up duration of 507 days. They underwent comprehensive workup in accordance with the ESC guidelines, including clinical assessment, electrocardiogram, echocardiography and biomarker testing. Results From the total population, 36 (5.7%) were diagnosed with HFpEF prior to cancer treatment initiation. Among these, 18 (50%) developed CTR-CVT during follow-up, mainly heart failure events (cancer-therapy related cardiac dysfunction or HFpEF decompensation). Independent of baseline characteristics, 233 patients (37.0%) developed a heart failure event during or after cancer treatment. Of these, 92 patients (14.6% of the total population, 39.5% of all HF events on treatment) developed a HFpEF event during or after cancer treatment. Of these HFpEF events, 42 patients (45.7%) were known with pre-existing cardiovascular disease, of whom only 14 (15.2%) with pre-existing HFpEF. In 50 patients (54.3%) the HFpEF diagnosis was made de novo during (or after) cancer treatment. Patients developing HFpEF were mostly female (n=54, 58.7%) and relatively young (mean age 62.0 years). Most HFpEF events occurred in breast cancer patients (n=32, 34.7%), prostate cancer patients (n=13, 14.1%) and multiple myeloma patients (n=9, 9.8%). Conclusions HFpEF is frequently overlooked, but conveys a high risk of developing CTR-CVT and should therefore be taken into account in the baseline risk stratification. Furthermore, HFpEF is responsible for an important morbidity burden during or after cancer cardiotoxic treatments, even in patients without prior diagnosis of HFpEF at baseline evaluation. Further studies are needed to evaluate if this population may benefit from specific management and treatment strategies in order to improve prognosis.Prevalence of HFpEF in cancer patients

Prediction of the burden and characteristics of coronary plaques by cardiorespiratory fitness

Abstract Background Cardiorespiratory fitness (CRF) and coronary plaque burden are both important predictors of mortality. Although mortality of coronary heart disease (CHD) is reduced, prevalence remains high and there is a need to improve early detection and preventive measures. How CRF relates to coronary plaque burden and composition in the general population is largely unknown. Purpose The aim was to study the relationship between CRF and the total coronary plaque burden, including subgroups of coronary plaques, in subjects without known CHD. Methods A random sample of participants from a large population-based echocardiographic reference range study aged 55-70 at baseline was included. Coronary plaque burden was assessed, on average, 4.0 years after the baseline evaluation using coronary computed tomography angiography (CCTA). The burden and characteristics of the coronary plaques were evaluated using a validated, commercially available, semi-automatic software that assessed all coronary territories including the left main, left anterior descending, circumflex, and right arteries. Coronary plaques were classified as dense calcified plaques, plaques with necrotic core, fibrous, and fibrous-fatty plaques. Baseline measures included cardiovascular risk factor assessment and measurement of peak oxygen consumption (VO2peak) assessed by treadmill cardiopulmonary exercise testing. Linear regression models were used to assess the impact of VO2peak on coronary plaque burden. In Model 1, we adjusted for sex and age, while Model 2 also included adjustments for non-HDL cholesterol, HbA1c, systolic blood pressure, smoking status, and body mass index. Results Of 845 invited to undergo CCTA, 707 (51% females) underwent CT scanning. Of these, 699 scans had acceptable quality for further analyses. Table 1 shows baseline characteristics and Table 2 shows the associations of VO2peak with coronary plaque burden. In the fully adjusted Model 2, there was a significant negative association of VO2peak with total plaque burden (β -0.18, R2 15%, p<0.001), while the association was not significant in Model 1 (p=0.54). Similarly, higher VO2peak significantly predicted a lower burden of dense calcified plaques, plaques with necrotic core, and fibrofatty plaques in both models (R2 3-17%, p≤0.01). The results were consistent whether the coronary plaques were evaluated across the entire coronary arteries (down to a diameter of 1.5 mm) or solely in the proximal segments. However, the predictive power of the models was relatively low with R2 of maximum 17%. Conclusion In a population without known CHD, CRF explained a modest part of the variation in coronary plaque burden. Considering CRF in risk prediction may enhance coronary artery disease prevention beyond traditional risk factors.

Incidence and risk factors for development of left ventricular hypertrophy in Fabry disease

Abstract Background Left ventricular hypertrophy (LVH) is the principal cardiac manifestation of Fabry disease (FD). This study aimed to determine the incidence and predictors of LVH development in a contemporary cohort of patients with FD and no LVH at baseline evaluation. Methods Consecutively referred adult (age ≥16 years) patients with FD were enrolled into an observational cohort study. Patients were prospectively followed in a specialist cardiomyopathy centre and the primary endpoint was the first detection of LVH (left ventricular mass index (LVMi) ≥115 g/m2 in men and ≥95 g/m2 in women). Results From a cohort of 393 patients, 214 (age 35.8 ±13.8 years; 61 [29%] males) had no LVH at first evaluation. During a median follow-up of 9.4 years (interquartile range [IQR] 4.7-12.7), 55 patients (24.6%) developed LVH. The estimated incidence of LVH was 11.3% (95% confidence interval [CI] 6.5-16.1) at 5 years, 29.1% (95%CI 21.5-36.7) at 10 years, and 45.0% (95%CI 33.8-62.4) at 15 years of follow-up. On multivariable analysis, independent predictors for LVH development were age (hazard ratio [HR] 1.04 [95%CI 1.02-1.06] per 1 year increase, p-value <0.001), male sex (HR 2.90 [95%CI 1.66-5.09], p-value <0.001), and an abnormal ECG (HR 3.10 [95%CI 1.72-5.57], p-value <0.001). The annual rate of change in LVMi was +2.77 (IQR 1.45-4.62) g/m2/year in males and +1.38 (IQR 0.09-2.85) g/m2/year in females (p-value <0.001). Conclusions Approximately one quarter of FD patients developed LVH during follow-up. Age, male sex, and ECG abnormalities were associated with a higher risk of developing LVH in patients with FD.Central Illustration

CMR characterisation of patients with heart failure and left bundle branch block

Abstract Introduction Cardiac magnetic resonance (CMR) is recommended internationally for tissue characterisation, volumetric assessment and assessment of prior myocardial infarction (1). Patients with left bundle branch block (LBBB) form a significant sub-group of individuals, however, there is limited data available to accurate determine whether LBBB is associated with any CMR-definable phenotypes. Aim We aimed to identify the distinctive cardiac magnetic resonance (CMR) features of patients with left bundle branch block (LBBB) and heart failure with reduced ejection fraction (HFrEF) of presumed non-ischaemic aetiology. Methods Participants from the MATCH (MyocArdial Tissue CHaracteristics in patients with heart failure according to glycaemic status) registry were prospectively enrolled. Exclusion criteria included: LVEF >40% at initial evaluation, established diagnosis of coronary artery disease, known presence of structural heart disease, suspected myocarditis, congenital heart disease and significantly impaired renal function. Following identification of HF, guideline-directed medical therapy was initiated based on the decision of the treating physician. LV recovery was defined as achieving ≥10% absolute improvement to a level of 40% or greater of LVEF from baseline evaluation upon the date of CMR quantification. Electrocardiograms were analysed to establish the presence or absence of LBBB. Results A total of 391 patients were recruited including 115 (29.4%) presenting with LBBB. Compared to controls, LBBB patients exhibited larger left ventricles and smaller right ventricles, but no differences were observed with respect to LVEF (35.8±12 vs. 38± 12 %, p=0.105) or right ventricular ejection fraction (RVEF). The prevalence of ischaemic scar (18.3% vs 21%, p=0.54), non-ischaemic fibrosis (25.2% vs 32.6%, p=0.15) and inducible ischaemia (6.1% vs. 7.6%, p=0.6) was comparable in patients with LBBB and those without. The overall rate of LV recovery was not significantly different between LBBB and non-LBBB patients (27.8% vs. 33%, p=0.32) from their baseline evaluation to the time of CMR assessment (70 [42 - 128] days). In the multivariate logistic regression, reduced LVEF remained an independent predictor of LV non-recovery in patients with LBBB, even after adjusting for gender and QRS duration (OR 0.93, 95%CI 0.87 – 0.99, p=0.03). In contrast, this association was not observed among patients without LBBB, whereas ischaemic scar was the primary predictor of LV non-recovery (OR 4.31, 95%CI 1.85 – 10.04, p=0.0007). Conclusion In this study patients presenting with a combination of HFrEF and LBBB had a larger LV cavity and smaller RV cavity than those without LBBB. However, there were no differences in the prevalence of ischaemic scar, non-ischaemic scar of inducible ischaemia according to the presence of absence of LBBB. Rates of LV recovery were similar between LBBB and non-LBBB patients.Clinical CMR ParametersSegmental Distributions

Phenotype progression in pediatric RASopathy-associated hypertrophic cardiomyopathy

Abstract Background RASopathy syndromes represent the second most common cause of hypertrophic cardiomyopathy (HCM) in children. RASopathy associated HCM (Ras-HCM) has been shown to differ both in cardiac phenotype and long-term outcomes from sarcomeric HCM. However, there is a lack of knowledge from large cohort studies of how the cardiac phenotype of Ras-HCM changes over time. Aim To describe cardiac phenotype changes over time in children with Ras-HCM Methods Retrospective data from 148 patients diagnosed with Ras-HCM aged <18 years with ³2 follow-up visits were included. Clinical and echocardiographic data were collected at baseline assessment, 1, 2, and 5 years of follow up. Separate analyses were performed for patients who survived, versus patients who died or had a heart transplant (censoring events). Results One-hundred-and-two (68.9%) patients with Noonan syndrome, 25 (16.9%) with Noonan-syndrome with multiple lentigines, 10 (6.8%) with Costello syndrome, 9 (6.1%) with cardio-facio-cutaneous syndrome and 2 (1.4%) patients with Noonan-like syndrome with a median age of diagnosis 0.16 years (0.01-0.89) were seen at a median baseline age of 1.41 years (0.37-5.71) and followed up for a median of 12.1 years (4.8-17.4). During follow up, 18 patients (12.2%) died at a median age of 1.8 years (0.5-8.7) and 17 (12.5%) had a left ventricular myectomy, at a median age of 7.0 years (3.1-12.7). At baseline evaluation, patients who died compared to those who survived had a lower median age [0.4 years (0.1-0.8) versus 2.3 years (0.5-7.6), p<0.001], a higher proportion of them had a NYHA class>I (54.5% vs 15.1%, p<0.001), a higher maximal left ventricular wall thickness (MLVWT) z-score [13.4 (7.5) vs 9.6 (6.2), p=0.04], a higher proportion of left ventricular outflow tract obstruction (LVOTO) [64.7% vs 43.8%, p=0.087] and a higher proportion of biventricular hypertrophy [75% vs 49.2%, p=0.045]. For survivors, the MLVWT z-score improved over follow up [+9.6(6.2) at baseline vs. +7.9(5.5) at 5 years, p=0.072], and the proportion of patients with LVOTO (43.8% at baseline vs. 27.9% at 5 years, p=0.019) and biventricular hypertrophy (49.2% at baseline vs. 35.5% at 5 years, p=0.012) decreased over follow up. Conclusion While at baseline evaluation Ras-HCM has a high burden of symptoms, biventricular hypertrophy and LVOTO for patients who die or have a heart transplant, we have demonstrated that for survivors, over follow up, the phenotype becomes milder.Table 1

Evolution over time of cardiac biomarkers, electrocardiographic and echocardiographic features in a large cohort of patients with wild-type transthyretin cardiac amyloidosis treated with tafamidis

Abstract Introduction Data on evolution of transthyretin wild-type cardiac amyloidosis (ATTRwt) during treatment with tafamidis is scarce. This hinders the quest for parameters of response and a priori treatment eligibility. Purpose To study the evolution of biomarkers, ECG, and echocardiographic features during early tafamidis treatment. Methods We prospectively collected data after 12-18 months of treatment in a single-centre database. Changes of NT-proBNP and high-sensitivity Troponin I (hs-cTnI) between baseline and follow-up evaluations (at 12 and 18 months) were tested for significance. For ECG and echocardiographic features, we considered baseline and the last available follow-up (median interval 11.1 months). Results We included 253 patients (median age 77[71-82]years; 90% males). Median (IQR) baseline NT-proBNP was 2472(1355-4749)ng/L, hs-cTnI 47(30-82)ng/L. Furosemide was administered in 58% of cases (median dose 25[25-50]mg/day). Compared to baseline, NT-proBNP was 2342(1316-4148)ng/L at 12 (p=0.886), and 2633(1393-6063)ng/L at 18 months (p=0.285), with 4% and 30% of patients showing ≥30% and ≥300ng/L increase at 12 and 18 months, respectively; hs-cTnI was 46(29-70)ng/L at 12 (p=0.947), and 44(25-68)ng/L at 18 months (p=0.866), with 35% and 7% showing a ≥20% increase at 12 and 18 months, respectively, and 21 (11.5% over 183 analyzable) with increase at 12 and reduction at 18 months. Patients on furosemide were 69% and 70% at 12 and 18 months, respectively; the dose increased to 37.5(25-75)mg/day at 18 months (p=0.009). At baseline, 117(47%) patients had history/permanent atrial fibrillation (AF). Forty-one(16%) had an implantable electronic device, 16(6%) underwent subsequent implantation. Median PR interval was 210(185-240)msec, trending toward prolongation (p=0.054). QRS duration increased (100[86-130]vs120[90-140]msec, p=0.004), together with conduction disturbances (left anterior fascicular block 30[21%]vs43[29%], p=0.036; right bundle branch block 14[10%]vs27[18%], p=0.002). AF prevalence raised from 19% to 25%. There were no significant changes in left ventricular (LV) geometry (septum thickness 18[16-20]vs18[16-20]mm, p=0.666; end-diastolic diameter 45±7vs45±8mm, p=0.434), systolic function (ejection fraction 51±10%vs49±11%, p=0.070), filling pressures (E/e’ 17[11-20]vs14.9[13-19], p=0.086) and left atrial size (mean volume 46±15vs48±13ml/m2, p=0.649). Tricuspid annular plane systolic excursion (18±4vs17±4mm) and pulmonary artery systolic pressure (40[33-45]vs36[30-45]mmHg) remained stable. Conclusions We did not observe neither improvement nor worsening of laboratory/instrumental variables within the first 12-18 months of tafamidis. There was a progression of electrical disorders. After initial progression hs-cTnI tended to improve. Extended follow-up and a matched case-control series will help identify possible later changes useful to monitor treatment response and effects of supporting heart failure treatments.

Dapagliflozin enhances arterial and venous compliance during exercise in heart failure with preserved ejection fraction

Abstract Background Systemic arterial compliance and venous capacitance are typically impaired in patients with heart failure with preserved ejection fraction (HFpEF), contributing to hemodynamic congestion with stress. Sodium-glucose cotransporter-2 inhibitors (SGLT2i) reduce hemodynamic congestion and improve clinical outcomes in patients with HFpEF, but the mechanisms remain unclear. Purpose This study tested the hypothesis that SGLT2i dapagliflozin would improve systemic arterial compliance and venous capacitance during exercise in patients with HFpEF. Methods In this secondary analysis from the RCT trial, patients with HFpEF underwent invasive hemodynamic exercise testing at baseline and following treatment for 24 weeks with dapagliflozin or placebo. Patients were required to display pulmonary capillary wedge pressure (PCWP) ≥25 mmHg during exercise at the time of baseline evaluation. Radial artery pressure (BP) was measured continuously using a fluid-filled catheter with transformation to aortic pressure, central hemodynamics were measured using high-fidelity micromanometers, and stressed blood volume was estimated (eSBV) from hemodynamic indices fit to a comprehensive cardiovascular model. Results A total of 37 patients completed the study and were included in this analysis (21 dapagliflozin and 16 placebo). Patients were predominantly women (24/37, 65%) and older (mean age 67 years). There was no statistically significant effect of dapagliflozin on resting BP, but dapagliflozin reduced systolic BP during peak exercise (estimated treatment difference [ETD], -18.8 mmHg, 95% CI: -33.9 to -3.7, P=0.016) (Figure 1A). Dapagliflozin improved exertional total arterial compliance (TAC) index (ETD, 0.06 mL/mmHg/m2, 95% CI: 0.003 to 0.11, P=0.039) (Figure 1B) and aortic root characteristic impedance (ETD, -2.6 mmHg/ml*sec, 95% CI: -5.1 to -0.03, P=0.048) during peak exercise, with no significant effect on systemic vascular resistance. Dapagliflozin reduced eSBV at rest and during peak exercise (ETD, -292 mmHg, 95% CI: -530 to -53, P=0.018) (Figure 1C), and improved venous capacitance evidenced by a decline in ratio of eSBV to total blood volume (ETD, -7.3%, 95% CI -13.3 to -1.3, P=0.020). Each of these effects of dapagliflozin during peak exercise were also observed during matched 20W exercise intensity. Improvements in TAC index and eSBV were correlated with decreases in body weight, and reduction in systolic BP with treatment was correlated with the change in eSBV during exercise (r=0.40, P=0.019) (Figure 2A). Decreases in BP were correlated with reduction in PCWP during exercise (r=0.56, P<0.001) (Figure 2B). Conclusion In patients with HFpEF, treatment with dapagliflozin improved systemic arterial compliance and venous capacitance during exercise, while reducing aortic characteristic impedance, suggesting a reduction in arterial wall stiffness. These vascular effects may partially explain the clinical benefits with SGLT2i in HFpEF.

Serial quantitative stress perfusion cardiac magnetic resonance in patients undergoing coronary artery bypass grafting; prediction of symptomatic benefit

Abstract Background Serial multiparametric cardiovascular magnetic resonance (CMR) in patients undergoing coronary artery bypass grafting (CABG) may provide mechanistic insight into dynamic and persistent abnormalities of the myocardium in patients with stable coronary artery disease (CAD). Objectives To assess for dynamic CMR markers of myocardial hypoperfusion and cardiac remodelling in patients undergoing CABG. Methods Patients with CAD awaiting elective CABG were recruited into an observational cohort study. Baseline evaluation included bloods, Seattle Angina Questionnaire-7, and adenosine stress perfusion CMR. Automated fully quantitative stress and rest myocardial blood flow was calculated, alongside assessment of the visual ischaemic burden. Native and post-contrast septal T1 indices were also measured. Repeat evaluation at 6-12 months post CABG was performed. Results Of 43 patients who underwent serial evaluation with CMR (mean age 62.1±9.3, median LVEF 68% [IQR: 62-73%]), there was improvement in the median visual ischaemic burden (18% [IQR: 11-21] vs 42% [IQR: 27-51], P<0.001), mean global stress myocardial blood flow (1.5±0.5 ml/min/g vs 1.3±0.5 ml/min/g, P=0.002) and median global myocardial perfusion reserve (2.4 [IQR: 1.7-2.8] vs 1.7 [IQR: 1.4-2.2], P=0.002) following CABG. Greater improvement in the SAQ-7 summary score was associated with a larger visual ischaemic burden at baseline (ρ=0.44, P=0.004) and a greater decrease in the visual ischaemic burden following CABG (ρ=-0.38, P=0.02). Quantitative MBF metrics did not associate with baseline or change in SAQ-7 summary score. Mean LV extracellular matrix volume decreased following CABG (16.6±3.6ml/m2 vs 18.2±4.6ml/m2, P=0.009). Conclusion Multiparametric CMR identifies dynamic changes in markers of myocardial perfusion and interstitial fibrosis in patients following CABG. Visual assessment of inducible myocardial hypoperfusion may identify patients who will derive the most symptomatic benefit from CABG. The results, however, suggest an important degree of residual inducible ischaemia and an unclear clinical role for CMR-derived MBF calculations.Serial CMR perfusion dataAssociation of SAQ with perfusion

Brainstem changes causing reversible RBD in patients with spontaneous intracranial hypotension: a longitudinal neuroimaging study.

This study aimed to investigate the prevalence of REM sleep behavior disorder (RBD) in patients with spontaneous intracranial hypotension (SIH) and longitudinally assess the effects of epidural blood patch (EBP) treatment on brainstem structures using a neuroimaging approach. Twenty-two participants (10 SIH patients and 12 controls) underwent 3-Tesla Magnetic Resonance Imaging (MRI) scans. Midbrain and pons areas were measured on T1-weighted scans at baseline in both groups and three months after the first EBP in SIH patients to determine any MRI structural changes. The RBD Single-Questionnaire was used to screen SIH patients with symptoms suggestive of RBD for polysomnographic (PSG) recording. Half of the SIH patients (5/10) exhibited PSG-confirmed RBD. Baseline evaluation revealed deep brain swelling (DBS) on MRI scans in SIH-RBD patients. Following EBP treatment, significant changes in midbrain and pons morphometry were associated with complete clinical remission of RBD. Cross-sectional analysis showed larger midbrain and pons areas in SIH patients (with and without RBD) compared to controls. A midbrain area of 200 mm2 was identified as a cut-off value distinguishing SIH patients (with and without RBD) from controls individually. Longitudinal analysis demonstrated lower midbrain areas at follow-up compared to baseline in SIH patients. The study suggests that brainstem morphometric changes may underlie reversible RBD in SIH patients. Midbrain area measurement could serve as a dynamic biomarker for SIH, particularly in the presence of RBD, offering insights for clinical practice.

Prognostic value of follow-up hemodynamics after initial treatment in pulmonary arterial hypertension

Abstract Background Hemodynamic variables such as right atrial pressure (RAP), cardiac index (CI) and mixed venous oxygen saturation (SvO2) have consistently been associated with survival in pulmonary arterial hypertension (PAH). The prognostic importance of hemodynamics after treatment initiation seems to be superior to baseline evaluation and stroke volume index (SVI) emerged as an independent prognostic parameter. New PAH treatments are, however, able to improve exercise capacity without increasing CI or SVI. Purpose The aim of this work was to define the prognostic role of follow-up hemodynamic parameters in a population of patients with idiopathic, hereditary, drug-induced PAH (I/H/D-PAH) and PAH associated with connective tissue disease (CTD-PAH) and congenital heart disease (CHD-PAH). Methods Treatment naïve PAH patients were assessed at baseline and at 1st follow-up (3-4 months after starting PAH-specific therapy; 1st F-UP) with 6-minute walk distance (6MWD), World Health Organization functional class (WHO-FC) and right heart catheterization (RHC). Collected hemodynamic parameters were: RAP, systolic, diastolic and mean pulmonary artery pressure (s/d/mPAP), CI, SVI, SvO2, pulmonary vascular resistance (PVR), pulmonary arterial compliance (PAC), cardiac efficiency (CE), pulmonary arterial elastance (Ea), resistance–compliance product (RC), right ventricular (RV) power, and RV stroke work index (RVSWI). The primary outcome was all cause death. We used stepwise Cox regression to assess variables obtained at baseline and at 1st F-UP. Results 794 patients with PAH were enrolled (54% I/H/D, 28% CTD, 18% CHD). A primary outcome occurred in 54% of patients over a median follow-up duration of 5.8 (2.4–11) years. In a multivariable model considering only baseline variables, no hemodynamic variables independently predicted prognosis but RAP. At first follow-up RHC (n=706), WHO-FC, 6-minute walk distance, RAP, and Ea were independently associated with death, adjusted for age, gender, and etiology of PAH. Because hemodynamic variables were highly correlated, we compared multivariable Cox regression models adding only variables with a correlation coefficient <0.6. In these models, RAP, Ea, PAC, CE, PVR, SvO2, CI, and SVI at follow-up RHC were independent predictors of death (Table). Conclusions Ea and right atrial pressure were the hemodynamic variables independently associated with death at 1st F-UP RHC after initial PAH treatment. These findings suggest that beyond improving RV function, RV afterload reduction can be considered a further treatment target.Table

High resolution computed tomography in systemic sclerosis: From diagnosis to follow-up.

Early diagnosis of interstitial lung disease (ILD) and pulmonary hypertension (PH) is crucial in systemic sclerosis (SSc) for both management and treatment. However, diagnosing SSc-ILD can be challenging because symptoms of lung involvement are often non-specific at the early stages of disease. High-resolution computed tomography (HRCT) of the chest is recognized as the most accurate imaging modality for baseline and follow-up evaluation of SSc-ILD. Key features of SSc-ILD on HRCT include a non-specific interstitial pneumonia (NSIP) pattern, with peripheral ground-glass opacities and extensive traction bronchiectasis. Less common HRCT manifestations include usual interstitial pneumonia (UIP) pattern, followed by diffuse alveolar damage (DAD), diffuse alveolar hemorrhage (DAH) and organizing pneumonia (OP). The extent of disease on HRCT is known to relate with prognosis and serial assessments can be helpful in monitoring disease progression or treatment response. We discuss the main chest computed tomography (CT) manifestations of SSc, highlighting the role of imaging at both baseline and follow-up evaluations.

The Journey to a FAIR CORE DATA SET for Diabetes Research in Germany

The German Center for Diabetes Research (DZD) established a core data set (CDS) of clinical parameters relevant for diabetes research in 2021. The CDS is central to the design of current and future DZD studies. Here, we describe the process and outcomes of FAIRifying the initial version of the CDS. We first did a baseline evaluation of the FAIRness using the FAIR Data Maturity Model. The FAIRification process and the results of this assessment led us to convert the CDS into the recommended format for spreadsheets, annotating the parameters with standardized medical codes, licensing the data set, enriching the data set with metadata, and indexing the metadata. The FAIRified version of the CDS is more suitable for data sharing in diabetes research across DZD sites and beyond. It contributes to the reusability of health research studies.

Data Ethics in Library Learning Analytics

Introduction: This study examines data handling and data ethics in library learning analytics research projects involving the use of data about students as library patrons, alongside a baseline evaluation of the benefits of library learning analytics to libraries practicing it. Methods: Citations were gathered via citation chain aggregation from the original Value of Academic Libraries report, then winnowed to projects with English-language artifacts documenting them, collection and/or analysis of library data about students, and a research question about the contribution of student library use to student success. Results and Discussion: Much of this research is reaching publication despite not employing best practices nor documenting respect for human-subjects research ethics, library-specific privacy and confidentiality ethics, and student data-privacy expectations. Very few projects create direct benefits to libraries. This result would not be possible without gaps or lapses in editorial processes, peer review, and upstream research guidance and ethics reviews. Conclusion: Ethics reforms are required at all stages of research and publication to prevent further unethical exploitation of patron data.

A multicenter bladder cancer MRI dataset and baseline evaluation of federated learning in clinical application

Bladder cancer (BCa), as the most common malignant tumor of the urinary system, has received significant attention in research on the clinical application of artificial intelligence algorithms. Nevertheless, it has been observed that certain investigations use data from various medical facilities to train models for BCa, which may pose a privacy risk. Given this concern, protecting patient privacy during machine learning algorithm training is a crucial aspect that requires substantial attention. One emerging machine learning paradigm that addresses this concern is federated learning (FL). FL enables multiple entities to collaboratively build machine learning models while preserving data privacy and security. In this study, we present a multicenter BCa magnetic resonance imaging (MRI) dataset. The dataset comprises 275 three-dimensional bladder T2-weighted MRI scans collected from four medical centers, and each scan includes diagnostic pathological labels for muscle invasion and pixel-level annotations of tumor contours. Four FL methods are used to assess the baseline of the dataset for both the task of diagnosing muscle-invasive bladder cancer and automatic bladder tumor lesion segmentation.

Associations between Kidney Disease Progression and Metabolomic Profiling in Stable Kidney Transplant Recipients-A 3 Year Follow-Up Prospective Study.

Background: kidney transplant recipients are exposed to multiple pathogenic pathways that may alter short and long-term allograft survival. Metabolomic profiling is useful for detecting potential biomarkers of kidney disease with a predictive capacity. This field is still under development in kidney transplantation and metabolome analysis is faced with analytical challenges. We performed a cross-sectional study including stable kidney transplant patients and aimed to search for relevant associations between baseline plasmatic and urinary metabolites and relevant outcomes over a follow-up period of 3 years. Methods: we performed a cross-sectional study including 72 stable kidney transplant patients with stored plasmatic and urinary samples at the baseline evaluation which were there analyzed by nuclear magnetic resonance in order to quantify and describe metabolites. We performed a 3-year follow-up and searched for relevant associations between renal failure outcomes and baseline metabolites. Between-group comparisons were made after classification by observed estimated glomerular filtration rate slope during the follow-up: positive slope and negative slope. Results: The mean estimated GFR (glomerular filtration rate) was higher at baseline in the patients who exhibited a negative slope during the follow-up (63.4 mL/min/1.73 m2 vs. 55.8 mL/min/1.73 m2, p = 0,019). After log transformation and division by urinary creatinine, urinary dimethylamine (3.63 vs. 3.16, p = 0.027), hippuric acid (7.33 vs. 6.29, p = 0.041), and acetone (1.88 vs. 1, p = 0.023) exhibited higher concentrations in patients with a negative GFR slope when compared to patients with a positive GFR slope. By computing a linear regression, a significant low-strength regression equation between the log 2 transformed plasmatic level of glycine and the estimated glomerular filtration rate was found (F (1,70) = 5.15, p = 0.026), with an R2 of 0.069. Several metabolites were correlated positively with hand grip strength (plasmatic tyrosine with r = 0.336 and p = 0.005 and plasmatic leucine with r = 0.371 and p = 0.002). Other urinary metabolites were found to be correlated negatively with hand grip strength (dimethylamine with r = -0.250 and p = 0.04, citric acid with r = -0.296 and p = 0.014, formic acid with r = -0.349 and p = 0.004, and glycine with r = -0.306 and p = 0.01). Conclusions: some metabolites had different concentrations compared to kidney transplant patients with negative and positive slopes, and significant correlations were found between hand grip strength and urinary and plasmatic metabolites.

Retinol-binding protein 4 is a potential biomarker of changes in lean mass in postmenopausal women.

Identifying biomarkers can help in the early detection of muscle loss and drive the development of new therapies. Research suggests a potential link between retinol-binding protein 4 (RBP4) and muscle mass, particularly in postmenopausal women. This study aimed to examine the association between baseline RBP4 levels and changes in appendicular lean mass (ALM), an indicator of muscle mass, in postmenopausal women. A 12-month follow-up period (n=153) included baseline and 12-month ALM assessments using DXA. ALM was normalized to squared height (ALMI). Baseline evaluations encompassed insulin resistance via HOMA-IR and immunoassay magnetic bead panel measurements of RPB4, IL-6, TNF-α, and IL-10. Postmenopausal women were categorized into higher (n=77) and lower (n=76) RPB4 groups based on baseline RPB4 values. Their changes in ALMI were compared using Mann-Whitney tests. General linear model was employed to evaluate the predictive power of baseline RBP4 for ALMI changes, adjusting for confounding variables: age, physical activity, smoking status, body fat, HOMA-IR, inflammatory markers (TNF-α and IL-6), and anti-inflammatory factor (IL-10). The higher RBP4 group exhibited a more pronounced reduction in ALMI compared to the lower RBP4 group (Higher RBP4 = -0.39kg/m2, 95% CI: -0.48 to -0.31kg/m2vs. Lower RBP4 = -0.24kg/m2, 95% CI: -0.32 to -0.15kg/m2, P=0.011). After adjusting for confounding factors, the association between baseline RBP4 changes and ALMI remained (b = -0.008, SE=0.002, P<0.001), indicating higher baseline RBP4 values linked to greater ALMI reduction. Our findings support RBP4 as a potential biomarker for changes in muscle mass in postmenopausal women.

Cardiac toxicity of HER-2 targeting antibody-drug conjugates: overview and clinical implications.

Antibody-drug conjugates (ADCs) have recently emerged as a promising therapeutic option that combine the specificity of monoclonal antibodies and the cytotoxic effect of chemotherapy. With numerous ADCs approved and on the market, a particular concern of ADCs that target HER-2 has been their cardiac side effects, in view of the crucial role of HER-2 in cardiac development and physiology. While rarely toxic and generally safe, numerous publications have outlined the consistent association of trastuzumab emtansine (T-DM1) and trastuzumab deruxtecan (T-DXd) with the development of cardiac toxicity. Despite not being clinically relevant in most cases, cardiac baseline evaluation, monitoring and early detection of cardiac adverse events remain pivotal with HER-2 targeting ADCs. This review aims to summarize and better characterize the complete cardiac toxicity profile of HER-2 ADCs, with the goal of improving clinical understanding of this adverse event, leading to better recognition, monitoring and management.

Spatial and seasonal variability of chlorophyll-a, total suspended matter, and colored dissolved organic matter in the Sundarban mangrove forest using earth observation and field data

The Sundarbans, the world's largest mangrove forest, confronts potential threats from various anthropogenic activities leading to degradation of its aquatic ecosystem. To examine the current status of the aquatic ecosystem, this study aimed to evaluate the spatial and seasonal fluctuation of three principal water quality attributes namely Chlorophyll-a (Chl-a), Total Suspended Matter (TSM), and Colored Dissolved Organic Matter (CDOM) in the complex tidal river systems of the Sundarban mangroves forest using earth observation and in-situ data. A set of two bio-optical algorithms, Ocean color-2 (OC-2) and Ocean color-3 (OC-3), were applied to measure Chl-a concentration, Green/NIR and the Red/NIR band ratio algorithms were used for TSM and the Case-2 Regional Coast Color (C2RCC) processor in the SNAP software was applied to obtain CDOM concentration in study area. A total of 50 in-situ samples were collected during post-monsoon and pre-monsoon to validate the results. Our results clearly demonstrated seasonal variability with higher Chl-a concentrations in post-monsoon than pre-monsoon. This was due to the OC-2 algorithm which produced better results with R2 = 0.73, RMSE = 0.27 for post-monsoon and R2 = 0.55, RMSE = 0.32 for pre-monsoon. Whilst, TSM concentration performed the best with R2 = 0.77; RMSE = 15.82 and R2 = 0.65; RMSE = 33.96 in post-monsoon and pre-monsoon according to the Green/NIR band ratio method. The nearshore and narrow waterway regions had the highest concentrations of TSM and Chl-a, whereas the offshore regions had the lowest. Strong association were observed between the in-situ and satellite derive absorption coefficient, aCDOM (m−1). The R2 for a CDOM during pre-monsoon was 0.65 and throughout the post-monsoon, it was 0.74. Pre-monsoon concentrations were found to be higher due to marine sources and higher wind speeds, possibly due to sediment resuspension. This kind of baseline evaluation will help to detect threats, direct preventive measures for the protection of biodiversity, and deepen our knowledge of these distinct ecosystems. The results will help develop flexible management and preservation plans that can adjust to both natural and man-made changes.

Improvement of laboratory markers of anaemia in the treatment of heavy menstrual bleeding with a 19.5-mg intrauterine device: a pilot study

Objectives To evaluate improvements in laboratory markers of anaemia (haemoglobin, haematocrit, serum iron, and ferritin) in women with subjective heavy menstrual bleeding (HMB) treated with the levonorgestrel 19.5-mg intrauterine device. Materials and methods We conducted a pilot study at the Department of Obstetrics and Gynaecology, University of Campinas, Faculty of Medical Sciences, Campinas, SP, Brazil. We compared anaemia markers in 73 women aged 18–48 years suffering from HMB, one year after placement of the IUD. Results The mean age of participants was 30.0 years (range 24–38); more than half were white, and the mean body mass index (kg/m2) was 27.0. Twenty (27.4%) participants exited the study due to loss to follow-up (n = 12; 16.4%), expulsion (n = 7; 9.6%) and uterine perforation (n = 1; 1.4%). One-year post-IUD placement, amenorrhoea was reported by 10 (13.7%) women. According to intention-to-treat and per protocol analyses, the proportion of women with normal haemoglobin levels significantly improved (p = 0.014 in both analyses), as did haematocrit (p < 0.001 in both analyses) and serum iron (p = 0.003 in both analyses) compared to baseline evaluations. The proportion of women with normal ferritin levels also improved (p < 0.001) in both analyses using a cut-off of 15 ng/ml, though no significant difference was observed using a 30 ng/ml cut-off (p = 0.083 in both analyses). Conclusion The levonorgestrel 19.5-mg IUD effectively improved laboratory markers of anaemia one year after placement in women with HMB.

Baseline evaluation of the World Health Organization (WHO) infection prevention and control (IPC) core components in Pacific Island Countries and Territories (PICTs)

BackgroundComprehensive infection prevention and control (IPC) programmes are proven to reduce the spread of healthcare-associated infections (HAIs) and antimicrobial resistance (AMR). However, published assessments of IPC programmes against the World Health Organization (WHO) IPC Core Components in Pacific Island Countries and Territories (PICTs) at the national and acute healthcare facility level are currently unavailable.MethodsFrom January 2022 to April 2023, a multi-country, cross-sectional study was conducted in PICTs. The self reporting survey was based on the WHO Infection Prevention Assessment Framework (IPCAF) that supports implementing the minimum requirements of the WHO eight core components of IPC programmes at both the national and facility level. The results were presented as a ‘traffic light’ (present, in progress, not present) matrix. Each PICT’s overall status in achieving IPC core components was summarised using descriptive statistics.ResultsFifteen PICTs participated in this study. Ten (67%) PICTs had national IPC programmes, supported mainly by IPC focal points (87%, n = 13), updated national IPC guidelines (80%, n = 12), IPC monitoring and feedback mechanisms (80%, n = 12), and waste management plans (87%, n = 13). Significant gaps were identified in education and training (20%, n = 3). Despite being a defined component in 67% (n = 10) of national IPC programmes, HAI surveillance and monitoring was the lowest scoring core component (13%, n = 2). National and facility level IPC guidelines had been adapted and implemented in 67% (n = 10) PICTs; however, only 40% (n = 6) of PICTs had a dedicated IPC budget, 40% (n = 6) had multimodal strategies for IPC, and 33% (n = 5) had daily environmental cleaning records.ConclusionsIdentifying IPC strengths, gaps, and challenges across PICTs will inform future IPC programme priorities and contribute to regional efforts in strengthening IPC capacity. This will promote global public health through the prevention of HAIs and AMR.