From riverbank to the sea: An initial assessment of plastic pollution along the Ciliwung River, Indonesia.

This study presents the first comprehensive analysis of anthropogenic debris on the riverbanks of the Ciliwung River, covering upstream to downstream areas. The mean of debris found in each measurement was 32.79 ± 15.38 items/m2 with a weight of 106.00 ± 50.23 g/m2. Plastic debris accounted for over 50 % of all litter items identified and represents 55 % by weight, signifying a significantly high prevalence compared to global studies examining litter along riverbanks. The majority of the plastics found originated from Single-use applications and were predominantly made from Styrofoam. This investigation demonstrated the importance of actions to reduce single use applications and to improve waste management strategies. This can be achieved through proactive initiatives coupled with adaptable approaches, such as implementing effective urban planning and enhancing waste collection capacity.

Hydroxyurea to prevent brain injury in children with sickle cell disease (HU Prevent)-A randomized, placebo-controlled phase II feasibility/pilot study.

Central nervous system (CNS) injury is common in sickle cell disease (SCD) and occurs early in life. Hydroxyurea is safe and efficacious for treatment of SCD, but high-quality evidence from randomized trials to estimate its neuroprotective effect is scant. HU Prevent was a randomized (1:1), double-blind, phase II feasibility/pilot trial of dose-escalated hydroxyurea vs. placebo for the primary prevention of CNS injury in children with HbSS or HbS-ß0-thalassemia subtypes of SCD age 12-48 months with normal neurological examination, MRI of the brain, and cerebral blood flow velocity. We hypothesized that hydroxyurea would reduce by 50% the incidence of CNS injury. Two outcomes were compared: primary-a composite of silent cerebral infarction, elevated cerebral blood flow velocity, transient ischemic attack, or stroke; secondary-a weighted score estimating the risk of suffering the consequences of stroke (the Stroke Consequences Risk Score-SCRS), based on the same outcome events. Six participants were randomized to each group. One participant in the hydroxyurea group had a primary outcome vs. four in the placebo group (incidence rate ratio [90% CI] 0.216 [0.009, 1.66], p = .2914) (~80% reduction in the hydroxyurea group). The mean SCRS score was 0.078 (SD 0.174) in the hydroxyurea group, 0.312 (SD 0.174) in the placebo group, p = .072, below the p-value of .10 often used to justify subsequent phase III investigations. Serious adverse events related to study procedures occurred in 3/41 MRIs performed, all related to sedation. These results suggest that hydroxyurea may have profound neuroprotective effect in children with SCD and support a definitive phase III study to encourage the early use of hydroxyurea in all infants with SCD.

Testing the Reliability of Optical Coherence Tomography to Measure Epidermal Thickness and Distinguish Volar and Nonvolar Skin.

In persons with limb loss, prosthetic devices cause skin breakdown, largely because residual limb skin (nonvolar) is not intended to bear weight such as palmoplantar (volar) skin. Before evaluation of treatment efficacy to improve skin resiliency, efforts are needed to establish normative data and assess outcome metric reliability. The purpose of this study was to use optical coherence tomography to (i) characterize volar and nonvolar skin epidermal thickness and (ii) examine the reliability of optical coherence tomography. Four orientations of optical coherence tomography images were collected on 33 volunteers (6 with limb loss) at 2 time points, and the epidermis was traced to quantify thickness by 3 evaluators. Epidermal thickness was greater (P < .01) for volar skin (palm) (265.1 ± 50.9 µm, n = 33) than for both nonvolar locations: posterior thigh (89.8 ± 18.1 µm, n = 27) or residual limb (93.4 ± 27.4 µm, n = 6). The inter-rater intraclass correlation coefficient was high for volar skin (0.887-0.956) but low for nonvolar skin (thigh: 0.292-0.391, residual limb: 0.211-0.580). Correlation improved when comparing only 2 evaluators who used the same display technique (palm: 0.827-0.940, thigh: 0.633-0.877, residual limb: 0.213-0.952). Despite poor inter-rater agreement for nonvolar skin, perhaps due to challenges in identifying the dermal-epidermal junction, this study helps to support the utility of optical coherence tomography to distinguish volar from nonvolar skin.

Extracorporeal photopheresis (ECP) in the treatment of chronic lung allograft dysfunction (CLAD): a prospective, multicentre, open-label, randomised controlled trial studying the addition of ECP to standard care in the treatment of bilateral lung transplant patients with CLAD (E-CLAD UK).

BACKGROUND: Long-term survival after lung transplantation is limited compared with other organ transplants. The main cause is development of progressive immune-mediated damage to the lung allograft. This damage, which can develop via multiple immune pathways, is captured under the umbrella term chronic lung allograft dysfunction (CLAD). Despite the availability of powerful immunosuppressive drugs, there are presently no treatments proven to reverse or reliably halt the loss of lung function caused by CLAD. The aim of the E-CLAD UK trial is to determine whether the addition of immunomodulatory therapy, in the form of extracorporeal photopheresis (ECP), to standard care is more efficacious at stabilising lung function in CLAD compared with standard care alone. METHODS AND ANALYSIS: E-CLAD UK is a Phase II clinical trial of an investigational medicinal product (Methoxsalen) delivered to a buffy coat prepared via an enclosed ECP circuit. Target recruitment is 90 bilateral lung transplant patients identified as having CLAD and being treated at one of the five UK adult lung transplant centres. Participants will be randomised 1:1 to intervention plus standard of care, or standard of care alone. Intervention will comprise nine ECP cycles spread over 20 weeks, each course involving two treatments of ECP on consecutive days. All participants will be followed up for a period of 24 weeks.The primary outcome is lung function stabilisation derived from change in forced expiratory volume in one second and forced vital capacity at 12 and 24 weeks compared with baseline at study entry. Other parameters include change in exercise capacity, health-related quality of life and safety. A mechanistic study will seek to identify molecular or cellular markers linked to treatment response and qualitative interviews will explore patient experiences of CLAD and the ECP treatment.A patient and public advisory group is integral to the trial from design to implementation, developing material to support the consent process and interview materials. ETHICS AND DISSEMINATION: The East Midlands-Derby Research Ethics Committee has provided ethical approval (REC 22/EM/0218). Dissemination will be via publications, patient-friendly summaries and presentation at scientific meetings. TRIAL REGISTRATION NUMBER: EudraCT number 2022-002659-20; ISRCTN 10615985.

Maralixibat in progressive familial intrahepatic cholestasis (MARCH-PFIC): a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial.

BACKGROUND: Progressive familial intrahepatic cholestasis (PFIC) is a group of autosomal recessive disorders, the most prevalent being BSEP deficiency, resulting in disrupted bile formation, cholestasis, and pruritus. Building on a previous phase 2 study, we aimed to evaluate the efficacy and safety of maralixibat-an ileal bile acid transporter inhibitor-in participants with all types of PFIC. METHODS: MARCH-PFIC was a multicentre, randomised, double-blind, placebo-controlled, phase 3 study conducted in 29 community and hospital centres across 16 countries in Europe, the Americas, and Asia. We recruited participants aged 1-17 years with PFIC with persistent pruritus (>6 months; average of ≥1·5 on morning Itch-Reported Outcome [Observer; ItchRO(Obs)] during the last 4 weeks of screening) and biochemical abnormalities or pathological evidence of progressive liver disease, or both. We defined three analysis cohorts. The BSEP (or primary) cohort included only those with biallelic, non-truncated BSEP deficiency without low or fluctuating serum bile acids or previous biliary surgery. The all-PFIC cohort combined the BSEP cohort with participants with biallelic FIC1, MDR3, TJP2, or MYO5B deficiencies without previous surgery but regardless of bile acids. The full cohort had no exclusions. Participants were randomly assigned (1:1) to receive oral maralixibat (starting dose 142·5 µg/kg, then escalated to 570 µg/kg) or placebo twice daily for 26 weeks. The primary endpoint was the mean change in average morning ItchRO(Obs) severity score between baseline and weeks 15-26 in the BSEP cohort. The key secondary efficacy endpoint was the mean change in total serum bile acids between baseline and the average of weeks 18, 22, and 26 in the BSEP cohort. Efficacy analyses were done in the intention-to-treat population (all those randomly assigned) and safety analyses were done in all participants who received at least one dose of study drug. This completed trial is registered with ClinicalTrials.gov, NCT03905330, and EudraCT, 2019-001211-22. FINDINGS: Between July 9, 2019, and March 4, 2022, 125 patients were screened, of whom 93 were randomly assigned to maralixibat (n=47; 14 in the BSEP cohort and 33 in the all-PFIC cohort) or placebo (n=46; 17 in the BSEP cohort and 31 in the all-PFIC cohort), received at least one dose of study drug, and were included in the intention-to-treat and safety populations. The median age was 3·0 years (IQR 2·0-7·0) and 51 (55%) of 93 participants were female and 42 (45%) were male. In the BSEP cohort, least-squares mean change from baseline in morning ItchRO(Obs) was -1·7 (95% CI -2·3 to -1·2) with maralixibat versus -0·6 (-1·1 to -0·1) with placebo, with a significant between-group difference of -1·1 (95% CI -1·8 to -0·3; p=0·0063). Least-squares mean change from baseline in total serum bile acids was -176 µmol/L (95% CI -257 to -94) for maralixibat versus 11 µmol/L (-58 to 80) for placebo, also representing a significant difference of -187 µmol/L (95% CI -293 to -80; p=0·0013). The most common adverse event was diarrhoea (27 [57%] of 47 patients on maralixibat vs nine [20%] of 46 patients on placebo; all mild or moderate and mostly transient). There were five (11%) participants with serious treatment-emergent adverse events in the maralixibat group versus three (7%) in the placebo group. No treatment-related deaths occurred. INTERPRETATION: Maralixibat improved pruritus and predictors of native liver survival in PFIC (eg, serum bile acids). Maralixibat represents a non-surgical, pharmacological option to interrupt the enterohepatic circulation and improve the standard of care in patients with PFIC. FUNDING: Mirum Pharmaceuticals.

Cardiac MRI evaluation of aortic biophysical properties in paediatric Turner syndrome.

BACKGROUND: Aortopathy in Turner syndrome is associated with aortic dilation, and the risk of dissection is increased when the aortic size index is ≥ 2-2.5 cm/m2. We evaluated the aortic biophysical properties in paediatric Turner syndrome using cardiac MRI to determine their relationship to aortic size index. METHODS: Turner syndrome patients underwent cardiac MRI to evaluate ventricular function, aortic dimensions, and biophysical properties (aortic stiffness index, compliance, distensibility, pulse wave velocity, and aortic and left ventricular elastance). Spearman correlation examined correlations between these properties and aortic size index. Data was compared to 10 controls. RESULTS: Of 25 Turner syndrome patients, median age 14.7 years (interquartile range: 11.0-16.8), height z score -2.7 (interquartile range: -2.92 - -1.54), 24% had a bicuspid aortic valve. Turner syndrome had increased diastolic blood pressure (p < 0.001) and decreased left ventricular end-diastolic (p < 0.001) and end-systolic (p = 0.002) volumes compared to controls. Median aortic size index was 1.81 cm/m2 (interquartile range: 1.45-2.1) and 7 had an aortic size index > 2 cm/m2. Aortic and left ventricular elastance were greater in Turner syndrome compared to controls (both p < 0.001). Increased aortic size index correlated with increased aortic elastance (r = 0.5, p = 0.01) and left ventricular elastance (r = 0.59, p = 0.002) but not aortic compliance. Higher ascending aortic areas were associated with increased aortic compliance (r = 0.44, p = 0.03) and left ventricular elastance (r = 0.49, p = 0.01). CONCLUSION: Paediatric Turner syndrome with similar aortic size index to controls showed MRI evidence of abnormal aortic biophysical properties. These findings point to an underlying aortopathy and provide additional parameters that may aid in determining risk factors for aortic dissection.

Effect of the age of garments used under real-life conditions on microfibre release from polyester and cotton clothing.

The release of microfibres from fabrics during laundering represents an important source of plastic and natural microfibres to aquatic environments. Garment age - how long the garment has been used - could be a key factor influencing the rate of release, yet most studies of microfibre shedding have only assessed newly manufactured products. To this end, we quantified microfibre release during laundering in domestic washing machines from polyester (PES) and cotton garments (n = 38) used in real-life conditions for periods between 1 and 31 years with different use intensities. In addition, to better understand the factors involved in microfibre releases, fibre composition (different PES percentages) and type of garments (T-shirts, polo shirts, uniforms, sports shirts, and sweatshirts) were examined. All garments released microfibres during washing, while the older garments presented higher releases for clothing with a PES/cotton blend. In general, older garments (15-31 years) released nearly twice as many fibres when washed than newer garments (1-10 years). The mass of microfibres released was consistently greater in garments with a higher proportion of cotton than PES (up to 1.774 mg g-1 in 2% PES and 0.366 mg g-1 in 100% PES fabrics), suggesting that cotton might be released more readily such that the relative proportion of PES in the garments could increase over time. Additionally, SEM images showed fibre damage, with fibres from the older garments exhibiting more peeling and splitting. While it is important to note that the overall environmental footprint is undoubtedly reduced by keeping garments in use for longer periods of time, older garments were shown to release more microfibres.

Features of the highway road network that generate or retain tyre wear particles.

The environmental accumulation of microplastics poses a formidable global challenge, with tyre wear particles (TWPs) emerging as major and potentially harmful contributors to this particulate pollution. A critical pathway for TWPs to aquatic environments is via road drainage. While drainage assets are employed worldwide, their effectiveness in retaining microplastics of highly variable densities (TWP ~ 1-2.5 g cm3) remains unknown. This study examines their ability to impede the transfer of TWPs from the UK Strategic Road Network (SRN) to aquatic ecosystems. Samples were collected from the influent, effluent and sediments of three retention ponds and three wetlands. The rate of TWP generation is known to vary in response to vehicle speed and direction. To ascertain the significance of this variability, we further compared the mass of TWPs in drainage from curved and straight sections of the SRN across eight drainage outfalls. Pyrolysis gas chromatography-mass spectrometry (Py-GC-MS) was used to quantify tyre wear using benzothiazole as a molecular marker for TWPs (with an internal standard benzothiazole-D4). Tyre wear was present in drainage from the SRN at concentrations of 2.86 ± 6 mg/L and was found within every sample analysed. Drainage from curved sections of the SRN contained on average a 40% greater TWP mass than straight sections but this was not significant. The presence of wetlands and retention ponds generally led to a reduction in TWP mass (74.9% ± 8.2). This effect was significant for retention ponds but not for wetlands; most probably due to variability among sites and sampling occasions. Similar drainage assets are used on a global scale; hence our results are of broad relevance to the management of TWP pollution.

Analysis of left ventricle regional myocardial motion for cardiac radioablation: Left ventricular motion analysis.

PURPOSE: Left ventricle (LV) regional myocardial displacement due to cardiac motion was assessed using cardiovascular magnetic resonance (CMR) cine images to establish region-specific margins for cardiac radioablation treatments. METHODS: CMR breath-hold cine images and LV myocardial tissue contour points were analyzed for 200 subjects, including controls (n = 50) and heart failure (HF) patients with preserved ejection fraction (HFpEF, n = 50), mid-range ejection fraction (HFmrEF, n = 50), and reduced ejection fraction (HFrEF, n = 50). Contour points were divided into segments according to the 17-segment model. For each patient, contour point displacements were determined for the long-axis (all 17 segments) and short-axis (segments 1-12) directions. Mean overall, tangential (longitudinal or circumferential), and normal (radial) displacements were calculated for the 17 segments and for each segment level. RESULTS: The greatest overall motion was observed in the control group-long axis: 4.5 ± 1.2 mm (segment 13 [apical anterior] epicardium) to 13.8 ± 3.0 mm (segment 6 [basal anterolateral] endocardium), short axis: 4.3 ± 0.8 mm (segment 9 [mid inferoseptal] epicardium) to 11.5 ± 2.3 mm (segment 1 [basal anterior] endocardium). HF patients exhibited lesser motion, with the smallest overall displacements observed in the HFrEF group-long axis: 4.3 ± 1.7 mm (segment 13 [apical anterior] epicardium) to 10.6 ± 3.4 mm (segment 6 [basal anterolateral] endocardium), short axis: 3.9 ± 1.3 mm (segment 8 [mid anteroseptal] epicardium) to 7.4 ± 2.8 mm (segment 1 [basal anterior] endocardium). CONCLUSIONS: This analysis provides an estimate of epicardial and endocardial displacement for the 17 segments of the LV for patients with normal and impaired LV function. This reference data can be used to establish treatment planning margin guidelines for cardiac radioablation. Smaller margins may be used for patients with higher degree of impaired heart function, depending on the LV segment.

Effect of lower body negative pressure on cardiac and cerebral function in postural orthostatic tachycardia syndrome: A pilot MRI assessment.

Postural orthostatic tachycardia syndrome (POTS) is characterized by an excessive heart rate (HR) response upon standing and symptoms indicative of inadequate cerebral perfusion. We tested the hypothesis that during lower body negative pressure (LBNP), individuals with POTS would have larger decreases in cardiac and cerebrovascular function measured using magnetic resonance (MR) imaging. Eleven patients with POTS and 10 healthy controls were studied at rest and during 20 min of -25 mmHg LBNP. Biventricular volumes, stroke volume (SV), cardiac output (Qc), and HR were determined by cardiac MR. Cerebral oxygen uptake (VO2 ) in the superior sagittal sinus was calculated from cerebral blood flow (CBF; MR phase contrast), venous O2 saturation (SvO2 ; susceptometry-based oximetry), and arterial O2 saturation (pulse oximeter). Regional cerebral perfusion was determined using arterial spin labelling. HR increased in response to LBNP (p < 0.001) with no group differences (HC: +9 ± 8 bpm; POTS: +13 ± 11 bpm; p = 0.35). Biventricular volumes, SV, and Qc decreased during LBNP (p < 0.001). CBF and SvO2 decreased with LBNP (p = 0.01 and 0.03, respectively) but not cerebral VO2 (effect of LBNP: p = 0.28; HC: -0.2 ± 3.7 mL/min; POTS: +1.1 ± 2.0 mL/min; p = 0.33 between groups). Regional cerebral perfusion decreased during LBNP (p < 0.001) but was not different between groups. These data suggest patients with POTS have preserved cardiac and cerebrovascular function.

Determinants of Impaired Peak Oxygen Uptake in Breast Cancer Survivors: JACC: CardioOncology Primer.

•Exercise intolerance is common among breast cancer survivors.•Exercise intolerance in breast cancer survivors is related to cardiac, vascular, and skeletal muscle impairments.•Holistic rehabilitation or pharmacological therapies are needed to address these impairments.

Genetic aetiologies of acute liver failure.

Acute liver failure (ALF) is a rare, rapidly evolving, clinical syndrome with devastating consequences where definitive treatment is by emergency liver transplantation. Establishing a diagnosis can be challenging and, historically, the cause of ALF was unidentified in up to half of children. However, recent technological and clinical advances in genomic medicine have led to an increasing proportion being diagnosed with monogenic aetiologies of ALF. The conditions encountered include a diverse group of inherited metabolic disorders each with prognostic and treatment implications. Often these disorders are clinically indistinguishable and may even mimic disorders of immune regulation or red cell disorders. Rapid genomic sequencing for children with ALF is, therefore, a key component in the diagnostic work up today. This review focuses on the monogenic aetiologies of ALF.

Clinical outcomes of ABCB4 heterozygosity in infants and children with cholestatic liver disease.

OBJECTIVES: Biallelic variants in the adenosine triphosphate binding cassette subfamily B member 4 (ABCB4) gene which encodes the multidrug resistance 3 protein (MDR3) leads to progressive familiar intrahepatic cholestasis type 3. However, monoallelic variants are increasingly recognized as contributing to liver disease in adults. Our aim was to describe the clinical characteristics of MDR3 heterozygous variants in a large cohort of infants and children with cholestatic liver disease. METHODS: The clinical and genotypic data on pediatric patients seen at King's College Hospital, London, between 2004 and 2022 and found to harbour heterozygous variants in ABCB4 were reviewed. RESULTS: Ninety-two patients amongst 1568 tested were identified with a monoallelic variant (5.9%). The most common presenting problem was conjugated hyperbilirubinemia (n = 46; 50%) followed by cholelithiasis (n = 12; 13%) and cholestatic hepatitis (n = 10; 11%). The median values of liver biochemistry at presentation were: GGT 105 IU/L and total bilirubin 86 µmol/L. Thirty-two genetic variants were identified including 22 missense (69%), 4 deletions (13%), 5 splice site (16%) and 1 termination (3%). At a median follow up of 1 year there was resolution of liver disease. CONCLUSIONS: Rare variants in ABCB4 were found amongst infants and children with cholestatic liver disease. The presenting problems were variable and abnormalities tended to normalize over time. Those with severe mutations could develop liver disease later in life when exposed to further insult and should be counseled appropriately.

Left ventricle segment-specific motion assessment for cardiac-gated radiosurgery.

Purpose.Cardiac radiosurgery is a non-invasive treatment modality for ventricular tachycardia, where a linear accelerator is used to irradiate the arrhythmogenic region within the heart. In this work, cardiac magnetic resonance (CMR) cine images were used to quantify left ventricle (LV) segment-specific motion during the cardiac cycle and to assess potential advantages of cardiac-gated radiosurgery.Methods.CMR breath-hold cine images and LV contour points were analyzed for 50 controls and 50 heart failure patients with reduced ejection fraction (HFrEF, EF < 40%). Contour points were divided into anatomic segments according to the 17-segment model, and each segment was treated as a hypothetical treatment target. The optimum treatment window (one fifth of the cardiac cycle) was determined where segment centroid motion was minimal, then the maximum centroid displacement and treatment area were determined for the full cardiac cycle and for the treatment window. Mean centroid displacement and treatment area reductions with cardiac gating were determined for each of the 17 segments.Results.Full motion segment centroid displacements ranged between 6-14 mm (controls) and 4-11 mm (HFrEF). Full motion treatment areas ranged between 129-715 mm2(controls) and 149-766 mm2(HFrEF). With gating, centroid displacements were reduced to 1 mm (controls and HFrEF), while treatment areas were reduced to 62-349 mm2(controls) and 83-393 mm2(HFrEF). Relative treatment area reduction ranged between 38%-53% (controls) and 26%-48% (HFrEF).Conclusion.This data demonstrates that cardiac cycle motion is an important component of overall target motion and varies depending on the anatomic cardiac segment. Accounting for cardiac cycle motion, through cardiac gating, has the potential to significantly reduce treatment volumes for cardiac radiosurgery.

Reference Values for Water-Specific T1 of the Liver at 3 T: T2*-Compensation and the Confounding Effects of Fat.

BACKGROUND: T1 mapping of the liver is confounded by the presence of fat. Multiparametric T1 mapping combines fat-water separation with T1-weighting to enable imaging of water-specific T1 (T1Water ), proton density fat fraction (PDFF), and T2* values. However, normative T1Water values in the liver and its dependence on age/sex is unknown. PURPOSE: Determine normative values for T1Water in the liver with comparison to MOLLI and evaluate a T2*-compensation approach to reduce T1 variability. STUDY TYPE: Prospective observational; phantoms. POPULATIONS: One hundred twenty-four controls (56 male, 18-75 years), 50 patients at-risk for liver disease (18 male, 30-76 years). FIELD STRENGTH/SEQUENCE: 2.89 T; Saturation-recovery chemical-shift encoded T1 Mapping (SR-CSE); MOLLI. ASSESSMENT: SR-CSE provided T1Water measurements, PDFF and T2* values in the liver across three slices in 6 seconds. These were compared with MOLLI T1 values. A new T2*-compensation approach to reduce T1 variability was evaluated test/re-test reproducibility. STATISTICAL TESTS: Linear regression, ANCOVA, t-test, Bland and Altman, intraclass correlation coefficient (ICC). P < 0.05 was considered statistically significant. RESULTS: Liver T1 values were significantly higher in healthy females (F) than males (M) for both SR-CSE (F-973 ± 78 msec, M-930 ± 72 msec) and MOLLI (F-802 ± 55 msec, M-759 ± 69 msec). T1 values were negatively correlated with age, with similar sex- and age-dependencies observed in T2*. The T2*-compensation model reduced the variability of T1 values by half and removed sex- and age-differences (SR-CSE: F-946 ± 36 msec, M-941 ± 43 msec; MOLLI: F-775 ± 35 msec, M-770 ± 35 msec). At-risk participants had elevated PDFF and T1 values, which became more distinct from the healthy cohort after T2*-compensation. MOLLI systematically underestimated liver T1 values by ~170 msec with an additional positive T1-bias from fat content (~11 msec/1% in PDFF). Reproducibility ICC values were ≥0.96 for all parameters. DATA CONCLUSION: Liver T1Water values were lower in males and decreased with age, as observed for SR-CSE and MOLLI acquisitions. MOLLI underestimated liver T1 with an additional large positive fat-modulated T1 bias. T2*-compensation removed sex- and age-dependence in liver T1, reduced the range of healthy values and increased T1 group differences between healthy and at-risk groups. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 1.

Sex-based differences in the phenotypic expression and prognosis of idiopathic non-ischaemic cardiomyopathy: a cardiovascular magnetic resonance study.

AIMS: We sought to characterize sex-related differences in cardiovascular magnetic resonance-based cardiovascular phenotypes and prognosis in patients with idiopathic non-ischaemic cardiomyopathy (NICM). METHODS AND RESULTS: Patients with NICM enrolled in the Cardiovascular Imaging Registry of Calgary (CIROC) between 2015 and 2021 were identified. Z-score values for chamber volumes and function were calculated as standard deviation from mean values of 157 sex-matched healthy volunteers, ensuring reported differences were independent of known sex-dependencies. Patients were followed for the composite outcome of all-cause mortality, heart failure admission, or ventricular arrhythmia. A total of 747 patients were studied, 531 (71%) males. By Z-score values, females showed significantly higher left ventricular (LV) ejection fraction (EF; median difference 1 SD) and right ventricular (RV) EF (difference 0.6 SD) with greater LV mass (difference 2.1 SD; P < 0.01 for all) vs. males despite similar chamber volumes. Females had a significantly lower prevalence of mid-wall striae (MWS) fibrosis (22% vs. 34%; P < 0.001). Over a median follow-up of 4.7 years, 173 patients (23%) developed the composite outcome, with equal distribution in males and females. LV EF and MWS were significant independent predictors of the outcome (respective HR [95% CI] 0.97 [0.95-0.99] and 1.6 [1.2-2.3]; P = 0.003 and 0.005). There was no association of sex with the outcome. CONCLUSION: In a large contemporary cohort, NICM was uniquely expressed in females vs. males. Despite similar chamber dilation, females demonstrated greater concentric remodelling, lower reductions in bi-ventricular function, and a lower burden of replacement fibrosis. Overall, their prognosis remained similar to male patients with NICM.