Combined brain-heart MRI identifies cardiac and white matter lesions in patients with systemic lupus erythematosus and/or antiphospholipid syndrome: A pilot study.

BACKGROUND: Antiphospholipid syndrome (APS) can occur primarily (PAPS) or secondary to another autoimmune disease (SAPS), most commonly systemic lupus erythematosus (SLE). Recently, we reported that subclinical brain involvement was highly prevalent in patients with autoimmune diseases, including SLE. We aimed to investigate whether patients with SLE, PAPS or SAPS and cardiac symptoms showed differences in cardiac/brain involvement based on combined brain-heart magnetic resonance imaging (MRI). METHODS: We prospectively recruited 15 patients with SAPS (86 % with SLE) and 3 patients with PAPS and compared their MRI findings to those of 13 patients with SLE from our previous publication. All patients underwent routine cardiovascular/neurological examination and standard echocardiography. RESULTS: No patients had abnormalities in routine clinical workup/echocardiography. The vast majority had white matter hyperintensities (WMHs) and all had evidence of myocardial fibrosis and/or inflammation. Patients with SAPS had a lower median WMH number [1.00 (1.00, 2.00)] than those with PAPS [3.00 (2.50, 3.00)] or SLE [2.00 (2.00, 3.00)] (p = 0.010). Subcortical and deep WM were highly prevalent. Periventricular WMHs were more frequent in patients with SLE [6 (46.2 %)] or PAPS [2 (66.7 %)] (p = 0.023). Higher lesion burdens (1 WMH vs. 2 WMHs vs. ≥ WMHs) were associated with the presence of cardiac fibrosis [3 (33.3 %) vs. 10 (83.3) vs. 7 (77.8), p = 0.039] and affected the deep and periventricular WM (p < 0.001 for both). CONCLUSION: In patients with PAPS, SAPS or SLE, cardiac symptoms and normal routine workup, combined brain-heart MRI identified abnormalities in both organs in the majority of patients. Combined brain-heart MRI offers excellent diagnostic value, but its incorporation into routine clinical practice should be further investigated. Clinical relevance statement Combined brain-heart magnetic resonance imaging in antiphospholipid syndrome may help to assess the presence of abnormalities in both organs.

Combined Brain-Heart Imaging in Takotsubo Syndrome: Towards a Holistic Patient Assessment.

Takotsubo syndrome (TTS) is a type of cardiomyopathy usually precipitated by either emotional or physical stress and potentially leading to reversible heart failure. There is emerging evidence indicating an interaction between the brain and the heart in patients with TTS. Nevertheless, these new insights are not reflected in the current clinical approach to TTS. The application of novel and existing imaging modalities for the evaluation of brain-heart interactions is an interesting approach that could potentially augment diagnostic and prognostic yield, as well as improve our pathophysiologic understanding in the context of TTS. In this opinion piece, we discuss the evidence supporting a brain-heart interaction in patients with TTS and discuss how a combined evaluation of brain-heart interactions could potentially be implemented.

The additive prognostic value of end-systolic pressure-volume relation by stress CMR in patients with known or suspected coronary artery disease.

PURPOSE: The difference between rest and peak stress end-systolic pressure-volume relation (ΔESPVR) is an afterload-independent index of left ventricular (LV) contractility. We assessed the independent prognostic value of ΔESPVR index by dipyridamole stress-cardiovascular magnetic resonance (CMR) in patients with known/suspected coronary artery disease (CAD). METHODS: We considered 196 consecutive patients (62.74 ± 10.66 years, 49 females). Wall motion and perfusion abnormalities at rest and peak stress were analysed. Replacement myocardial fibrosis was detected by late gadolinium enhancement (LGE) technique. The ESPVR was evaluated at rest and peak stress from raw measurement of systolic arterial pressure and end-systolic volume by biplane Simpson's method. RESULTS: A reduced ΔESPVR index (≤ 0.02 mmHg/mL/m2) was found in 88 (44.9%) patients and it was associated with a lower LV ejection fraction (EF) and with a higher frequency of abnormal stress CMR and myocardial fibrosis. During a mean follow-up of 53.17 ± 28.21 months, 50 (25.5%) cardiac events were recorded: 5 cardiac deaths, 17 revascularizations, one myocardial infarction, 23 hospitalisations for heart failure or unstable angina, and 4 ventricular arrhythmias. According to Cox regression analysis, diabetes, family history, LVEF, abnormal stress CMR, myocardial fibrosis, and reduced ΔESPVR were significant univariate prognosticators. In the multivariate analysis the independent predictors were ΔESPVR index ≤ 0.02 mmHg/mL/m2 (hazard ratio-HR = 2.58, P = 0.007), myocardial fibrosis (HR = 2.13, P = 0.036), and diabetes (HR = 2.33, P = 0.012). CONCLUSION: ΔESPVR index by stress-CMR was independently associated with cardiac outcomes in patients with known/suspected CAD, in addition to replacement myocardial fibrosis and diabetes. Thus, the assessment of ΔESPVR index may be included into the standard stress-CMR exam to further stratify the patients.

Oxidative Stress and Antioxidant Status in Adult Patients with Transfusion-Dependent Thalassemia: Correlation with Demographic, Laboratory, and Clinical Biomarkers.

Iron overload in beta transfusion-dependent thalassemia (ß-TDT) may provoke oxidative stress and reduction of the antioxidant defenses, with serious consequences for the disease course and complications. The present study evaluated the oxidant/antioxidant status of ß-TDT patients and its correlation with demographic, clinical, laboratory, and instrumental biomarkers. The OXY-adsorbent assay and the d-ROMs (Diacron, Grosseto, Italy) were evaluated in 58 ß-TDT patients (mean age: 37.55 ± 7.83 years, 28 females) enrolled in the Extension-Myocardial Iron Overload in Thalassemia Network. Iron overload was quantified with R2* magnetic resonance imaging. Mean OXY was 323.75 ± 113.19 µmol HClO/mL and 39 (67.2%) patients showed a decreased OXY-Adsorbent level (<350 µmol HClO/mL), of whom 22 (37.9%) showed severely reduced levels. Mean d-ROMs was 305.12 ± 62.19 UA; 12 (20.7%) patients showed oxidative stress, and 4 (6.9%) elevated oxidative stress. OXY showed a significant negative correlation with global and segmental cardiac iron levels. D-ROMs levels significantly correlated with markers of cardiovascular risk (aging, glycemia, and N-terminal pro-B-type natriuretic peptide). Antioxidant depletion is frequent in ß-TDT patients, where OXY might serve as additive biomarker to assess heart iron status, whereas the d-ROMs might be helpful to assess the cardiovascular risk burden.

Potential Benefits of Photon-Counting CT in Dental Imaging: A Narrative Review.

Background/Objectives: Advancements in oral imaging technology are continually shaping the landscape of dental diagnosis and treatment planning. Among these, photon-counting computed tomography (PCCT), introduced in 2021, has emerged as a promising, high-quality oral technology. Dental imaging typically requires a resolution beyond the standard CT systems achievable with the specialized cone-beam CT. PCCT can offer up to 100 µm resolution, improve soft-tissue contrast, and provide faster scanning times, which are crucial for detailed dental diagnosis and treatment planning. Using semiconductor detectors, PCCT produces sharper images and can potentially reduce the number of scans required, thereby decreasing patient radiation exposure. This review aimed to explore the potential benefits of PCCT in dental imaging. Methods: This review analyzed the literature on PCCT in dental imaging from January 2010 to February 2024, sourced from PubMed, Scopus, and Web of Science databases, focusing on high-resolution, patient safety, and diagnostic efficiency in dental structure assessment. We included English-language articles, case studies, letters, observational studies, and randomized controlled trials while excluding duplicates and studies unrelated to PCCT's application in dental imaging. Results: Studies have highlighted the superiority of PCCT in reducing artifacts, which are often problematic, compared to conventional CBCT and traditional CT scans, due to metallic dental implants, particularly when used with virtual monoenergetic imaging and iterative metal artifact reduction, thereby improving implant imaging. This review acknowledges limitations, such as the potential for overlooking other advanced imaging technologies, a narrow study timeframe, the lack of real-world clinical application data in this field, and costs. Conclusions: PCCT represents a promising advancement in dental imaging, offering high-resolution visuals, enhanced contrast, and rapid scanning with reduced radiation exposure.

Multiparametric Cardiac Magnetic Resonance Assessment in Sickle Beta Thalassemia.

Cardiac involvement in sickle beta thalassemia (Sß-thal) patients has been poorly investigated. We aimed to evaluate cardiac function and myocardial iron overload by cardiovascular magnetic resonance (CMR) in patients with Sß-thal. One-hundred and eleven Sß-thal patients consecutively enrolled in the Myocardial Iron Overload in Thalassemia (MIOT) network were studied and compared with 46 sickle cell anemia (SCA) patients and with 111 gender- and age- matched healthy volunteers. Cine images were acquired to quantify biventricular function. Myocardial iron overload (MIO) was assessed by the T2* technique, while macroscopic myocardial fibrosis was evaluated by the late gadolinium enhancement (LGE) technique. In Sß-thal and SCA patients, the morphological and functional CMR parameters were not significantly different, except for the left atrial area and left ventricular (LV) stroke volume, indexed by body surface area (p = 0.023 and p = 0.048, respectively), which were significantly higher in SCA patients. No significant differences between the two groups were found in terms of myocardial iron overload and macroscopic myocardial fibrosis. When compared to healthy subjects, Sß-thal patients showed significantly higher bi-atrial and biventricular parameters, except for LV ejection fraction, which was significantly lower. The CMR analysis confirmed that Sß-thal and SCA patients are phenotypically similar. Since Sß-thal patients showed markedly different morphological and functional indices from healthy subjects, it would be useful to identify Sß-thal/SCA-specific bi-atrial and biventricular reference values.

Overcoming the Boundaries of Heart Warm Ischemia in Donation After Circulatory Death: The Padua Case.

A 45 year old male obese patient with a previous history of repaired congenital heart disease developed worsening heart failure making heart transplantation listing mandatory. Unfortunately, due to his anthropometric measures, the search for a suitable brain-dead donor was unsuccessful. For this reason, he accepted to be enrolled in the controlled donation after circulatory death (cDCD) program. According to the Italian Law regulating death declaration after cardiac arrest (no-touch period of 20 minutes-one of the longest in the world), we faced a 34 minute cardiac asystole, after which the heart was recovered through a thoraco-abdominal normothermic regional perfusion excluding the epiaortic vessels. The heart was then preserved by means of cold static storage. Heart transplantation was performed successfully without any signs of primary graft failure. Postoperative endomyocardial biopsies were negative for acute cellular and antibody-mediated rejection. Furthermore, echocardiographic and cardiac magnetic resonance evaluation of the heart did not show any functional abnormalities. The patient was discharged on post-operative day (POD) #39 in good clinical conditions.

Longitudinal prospective comparison of pancreatic iron by magnetic resonance in thalassemia patients transfusion-dependent since early childhood treated with combination deferiprone-desferrioxamine vs deferiprone or deferasirox monotherapy.

BACKGROUND: In transfusion-dependent thalassemia patients who started regular transfusions in early childhood, we prospectively and longitudinally evaluated the efficacy on pancreatic iron of a combined deferiprone (DFP) + desferrioxamine (DFO) regimen versus either oral iron chelator as monotherapy over a follow-up of 18 months. MATERIALS AND METHODS: We selected patients consecutively enrolled in the Extension-Myocardial Iron Overload in Thalassemia network who received a combined regimen of DFO+DFP (No.=28) or DFP (No.=61) or deferasirox (DFX) (No.=159) monotherapy between the two magnetic resonance imaging scans. Pancreatic iron overload was quantified by the T2* technique. RESULTS: At baseline no patient in the combined treatment group had a normal global pancreas T2* (≥26 ms). At follow-up the percentage of patients who maintained a normal pancreas T2* was comparable between the DFP and DFX groups (57.1 vs 70%; p=0.517).Among the patients with pancreatic iron overload at baseline, global pancreatic T2* values were significantly lower in the combined DFO+DFP group than in the DFP or DFX groups. Since changes in global pancreas T2* values were negatively correlated with baseline pancreas T2* values, the percent changes in global pancreas T2* values, normalized for the baseline values, were considered. The percent changes in global pancreas T2* values were significantly higher in the combined DFO+DFP group than in either the DFP (p=0.036) or DFX (p=0.030) groups. DISCUSSION: In transfusion-dependent patients who started regular transfusions in early childhood, combined DFP+DFO was significantly more effective in reducing pancreatic iron than was either DFP or DFX.

Liver T1 and T2 mapping in a large cohort of healthy subjects: normal ranges and correlation with age and sex.

OBJECTIVE: We established normal ranges for native T1 and T2 values in the human liver using a 1.5 T whole-body imager (General Electric) and we evaluated their variation across hepatic segments and their association with age and sex. MATERIALS AND METHODS: One-hundred healthy volunteers aged 20-70 years (50% females) underwent MRI. Modified Look-Locker inversion recovery and multi-echo fast-spin-echo sequences were used to measure hepatic native global and segmental T1 and T2 values, respectively. RESULTS: T1 and T2 values exhibited good intra- and inter-observer reproducibility (coefficient of variation < 5%). T1 value over segment 4 was significantly lower than the T1 values over segments 2 and 3 (p < 0.0001). No significant regional T2 variability was detected. Segmental and global T1 values were not associated with age or sex. Global T2 values were independent from age but were significantly lower in males than in females. The lower and upper limits of normal for global T1 values were, respectively, 442 ms and 705 ms. The normal range for global T2 values was 35 ms-54 ms in males and 39 ms-54 ms in females. DISCUSSION: Liver T1 and T2 mapping is feasible and reproducible and the provided normal ranges may help to establish diagnosis and progression of various liver diseases.

Nodal staging with MRI after neoadjuvant chemo-radiotherapy for locally advanced rectal cancer: a fast and reliable method.

OBJECTIVES: In patients with locally advanced rectal carcinoma (LARC), negative nodal status after neoadjuvant chemoradiotherapy (nCRT) may allow for rectum-sparing protocols rather than total mesorectal excision; however, current MRI criteria for nodal staging have suboptimal accuracy. The aim of this study was to compare the diagnostic accuracy of different MRI dimensional criteria for nodal staging after nCRT in patients with LARC. MATERIALS AND METHODS: Patients who underwent MRI after nCRT for LARC followed by surgery were retrospectively included and divided into a training and a validation cohort of 100 and 39 patients, respectively. Short-, long-, and cranial-caudal axes and volume of the largest mesorectal node and nodal status based on European Society of Gastrointestinal Radiology consensus guidelines (i.e., ESGAR method) were assessed by two radiologists independently. Inter-reader agreement was assessed in the training cohort. Histopathology was the reference standard. ROC curves and the best cut-off were calculated, and accuracies compared with the McNemar test. RESULTS: The study population included 139 patients (median age 62 years [IQR 55-72], 94 men). Inter-reader agreement was high for long axis (κ = 0.81), volume (κ = 0.85), and ESGAR method (κ = 0.88) and low for short axis (κ = 0.11). Accuracy was similar (p > 0.05) for long axis, volume, and ESGAR method both in the training (71%, 74%, and 65%, respectively) and in the validation (83%, 78%, and 75%, respectively) cohorts. CONCLUSION: Accuracy of the measurement of long axis and volume of the largest lymph node is not inferior to the ESGAR method for nodal staging after nCRT in LARC. CLINICAL RELEVANCE STATEMENT: In MRI restaging of rectal cancer, measurement of the long axis or volume of largest mesorectal lymph node after preoperative chemoradiotherapy is a faster and reliable alternative to ESGAR criteria for nodal staging. KEY POINTS: • Current MRI criteria for nodal staging in locally advanced rectal cancer after chemo-radiotherapy have suboptimal accuracy and are time-consuming. • Measurement of long axis or volume of the largest mesorectal lymph node on MRI showed good accuracy for assessment of loco-regional nodal status in locally advanced rectal cancer. • MRI measurement of the long axis and volume of largest mesorectal lymph node after chemo-radiotherapy could be a faster and reliable alternative to ESGAR criteria for nodal staging.

Precocious Puberty Diagnoses Spike, COVID-19 Pandemic, and Body Mass Index: Findings From a 4-year Study.

Context: Since the COVID-19 outbreak, the number of girls with suspected precocious puberty has increased. Objective: To compare the incidence of idiopathic central precocious puberty (ICPP) during COVID-19 with that of the previous 4 years. Methods: Anthropometric, biochemical, and radiological parameters were collected between January 2016 and June 2021 from 133 girls who met the Rapidly Progressive ICPP criteria (RP-ICPP). Results: We found a higher incidence of RP-ICPP between March 2020 and June 2021 (group 2) compared with January 2016 through March 2020 (group 1) (53.5% vs 41.1%); 2021 showed the highest annual incidence (P < .05). Group 1 and group 2 differed in age at diagnosis (7.96 ± 0.71 vs 7.61 ± 0.94; P < .05), mean Tanner stage (2.86 ± 0.51 vs 2.64 ± 0; P < .05), and in the time between the appearance of thelarche and diagnosis (0.93 ± 0.75 vs 0.71 ± 0.62 years, P < .05). There was an increase in the number of girls aged <8 years in group 2 and a significantly higher number of girls aged >8 years was found in group 1 (42 in group 1 vs 20 in group 2, P < 0.05). Overall body mass index SD score showed higher values ​​in group 2 (1.01 ± 1.23 vs 0.69 ± 1.15; P = .18), which spent an average of 1.94 ± 1.81 hours per day using electronic devices; 88.5% of this group stopped any physical activity. Conclusions: A spike in new diagnoses of idiopathic (1.79-fold higher) and RP-CPP coincided with the COVID-19 pandemic. The incidence of RP-ICPP was 1.3-fold higher during COVID-19 with a trend toward an increase in body mass index SD score. The expanding use of digital devices and the reduction of daily physical activity represent possible risk factors.

Impact of the COVID-19 Pandemic on Iron Overload Assessment by MRI in Patients with Hemoglobinopathies: The E-MIOT Network Experience.

BACKGROUND: The E-MIOT (Extension-Myocardial Iron Overload in Thalassemia) project is an Italian Network assuring high-quality quantification of tissue iron overload by magnetic resonance imaging (MRI). We evaluated the impact of the COVID-19 pandemic on E-MIOT services. METHODS: The activity of the E-MIOT Network MRI centers in the year 2020 was compared with that of 2019. A survey evaluated whether the availability of MRI slots for patients with hemoglobinopathies was reduced and why. RESULTS: The total number of MRI scans was 656 in 2019 and 350 in 2020, with an overall decline of 46.4% (first MRI: 71.7%, follow-up MRI: 36.9%), a marked decline (86.9%) in the period March-June 2020, and a reduction in the gap between the two years in the period July-September. A new drop (41.4%) was recorded in the period October-December for two centers, due to the general reduction in the total amount of MRIs/day for sanitization procedures. In some centers, patients refused MRI scans for fear of getting COVID. Drops in the MRI services >80% were found for patients coming from a region without an active MRI site. CONCLUSIONS: The COVID-19 pandemic had a strong negative impact on MRI multi-organ iron quantification, with a worsening in the management of patients with hemoglobinopathies.

Biventricular Tissue Tracking with Cardiovascular Magnetic Resonance: Reference Values of Left- and Right-Ventricular Strain.

We derived reference values of left-ventricular (LV) and right-ventricular (RV) strain parameters in a cohort of 100 healthy subjects by feature tracking cardiac magnetic resonance (FT-CMR). Global and regional strain values were calculated for the LV; circumferential and radialSAX strain parameters were derived from the short-axis (SAX) stack, while longitudinal and radialLAX strain parameters were assessed in three long-axis (LAX) views. Only global longitudinal strain (GLS) was calculated for the RV. Peak global LV circumferential strain was -16.7% ± 2.1%, LV radialSAX strain was 26.4% ± 5.1%, LV radialLAX strain was 31.1% ± 5.2%, LV GLS was -17.7% ± 1.9%, and RV GLS was -23.9% ± 4.1%. Women presented higher global LV and RV strain values than men; all strain values presented a weak relationship with body surface area, while there was no association with age or heart rate. A significant association was detected between all LV global strain measures and LV ejection fraction, while RV GLS was correlated to RV end-diastolic volume. The intra- and inter-operator reproducibility was good for all global strain measures. In the regional analysis, circumferential and radial strain values resulted higher at the apical level, while longitudinal strain values were higher at the basal level. The assessment of cardiac deformation by FT-CMR is feasible and reproducible and gender-specific reference values should be used.

Consensus on the assessment of systemic sclerosis-associated primary heart involvement: World Scleroderma Foundation/Heart Failure Association guidance on screening, diagnosis, and follow-up assessment.

Introduction: Heart involvement is a common problem in systemic sclerosis. Recently, a definition of systemic sclerosis primary heart involvement had been proposed. Our aim was to establish consensus guidance on the screening, diagnosis and follow-up of systemic sclerosis primary heart involvement patients. Methods: A systematic literature review was performed to investigate the tests used to evaluate heart involvement in systemic sclerosis. The extracted data were categorized into relevant domains (conventional radiology, electrocardiography, echocardiography, cardiac magnetic resonance imaging, laboratory, and others) and presented to experts and one patient research partner, who discussed the data and added their opinion. This led to the formulation of overarching principles and guidance statements, then reviewed and voted on for agreement. Consensus was attained when the mean agreement was ⩾7/10 and of ⩾70% of voters. Results: Among 2650 publications, 168 met eligibility criteria; the data extracted were discussed over three meetings. Seven overarching principles and 10 guidance points were created, revised and voted on. The consensus highlighted the importance of patient counseling, differential diagnosis and multidisciplinary team management, as well as defining screening and diagnostic approaches. The initial core evaluation should integrate history, physical examination, rest electrocardiography, trans-thoracic echocardiography and standard serum cardiac biomarkers. Further investigations should be individually tailored and decided through a multidisciplinary management. The overall mean agreement was 9.1/10, with mean 93% of experts voting above 7/10. Conclusion: This consensus-based guidance on screening, diagnosis and follow-up of systemic sclerosis primary heart involvement provides a foundation for standard of care and future feasibility studies that are ongoing to support its application in clinical practice.

Self-oriented anisotropic structure of G-hydrogels as a delicate balance between attractive and repulsive forces.

Guanine (G) hydrogels are very attractive materials made by the supramolecular organization of G-derivatives in water. In this paper, hydrogels composed of guanosine 5'-monophosphate (GMP) and guanosine (Gua), that make long, flexible and knotted G-quadruplexes, were investigated by small- and wide-angle X-ray scattering (SAXS and WAXS) to comprehend the origin of their unique orientational properties. The SAXS intensity, analysed at a fixed scattering vector modulus Q as a function of polar angle, allowed us to derive the Maier-Saupe orientation parameter m. The strong dependence of m on hydrogel composition and temperature demonstrated that the preferred orientation is controlled by the quadruplex surface charge and flexibility. Indeed, a possible correlation between the orientation parameter m and the quadruplex-to-quadruplex lateral interactions was explored. Results confirmed that the balance between attractive and repulsive interactions plays a main role in the orientational anisotropy: quadruplex clusters lose their orientational properties when attractive interactions decrease. The key role of the number of negative charges per unit length of the G-quadruplex filaments was confirmed by Atomic Force Microscopy (AFM) observations. Indeed, directionality histograms showed that in the presence of a large amount of Gua, G-quadruplexes follow preferential orientations other than those related to the strong interactions with the K+ pattern on the mica surface. The fact that lateral quadruplex-to-quadruplex interactions, even in the presence of external (opposing) forces, can tune the hydrogel alignment in a given preferred direction provides novel possibilities for scaffold/3D printing applications.

Medical Radiology: Current Progress.

Recently, medical radiology has undergone significant improvements in patient management due to advancements in image acquisition by the last generation of machines, data processing, and the integration of artificial intelligence. In this way, cardiovascular imaging is one of the fastest-growing radiological subspecialties. In this study, a compressive review was focused on addressing how and why CT and MR have gained a I class indication in most cardiovascular diseases, and the potential impact of tissue and functional characterization by CT photon counting, quantitative MR mapping, and 4-D flow. Regarding rectal imaging, advances in cancer imaging using diffusion-weighted MRI sequences for identifying residual disease after neoadjuvant chemoradiotherapy and [18F] FDG PET/MRI were provided for high-resolution anatomical and functional data in oncological patients. The results present a large overview of the approach to the imaging of diffuse and focal liver diseases by US elastography, contrast-enhanced US, quantitative MRI, and CT for patient risk stratification. Italy is currently riding the wave of these improvements. The development of large networks will be crucial to create high-quality databases for patient-centered precision medicine using artificial intelligence. Dedicated radiologists with specific training and a close relationship with the referring clinicians will be essential human factors.

The impact of HCV chronic positivity and clearance on extrahepatic morbidity in thalassemia major patients: an observational study from MIOT Network.

BACKGROUND: No study has evaluated the effect of hepatitis C virus (HCV) infection on the wide spectrum of complications affecting patients with thalassemia. OBJECTIVES: This multicenter study prospectively assessed the relationship of HCV infection with diabetes mellitus and cardiovascular complications in patients with thalassemia major (TM). METHODS: We considered 1057 TM patients (539 females; 29.79±10.08 years) enrolled in the MIOT Network and categorized into 4 groups: negative patients (group 1a, N=460), patients who spontaneously cleared the virus within 6months (group 1b, N=242), patients who eradicated the virus after the treatment with antiviral therapy (group 2, N=102), and patients with chronic HCV infection (group 3, N=254). RESULTS: Group 1a and 1b were considered as a unique group (group 1). For both groups 1 and 3, a match 1:1 for age and sex with group 2 was performed. The effective study cohort consisted of 306 patients (three groups of 102 patients). During a mean follow-up of 67.93±39.20months, the group 3 experienced a significantly higher % increase/month in aspartate transaminase levels and left ventricular mass index than both groups 1 and 2. The changes in iron overload indexes were comparable among the three groups. Compared to group 1, the chronic HCV group showed a significantly higher risk of diabetes (hazard ratio-HR=5.33; p=0.043) and of cardiovascular diseases (HR=3.80; p=0.034). CONCLUSION: Chronic HCV infection is associated with a significant higher risk of diabetes mellitus and cardiovascular complications in TM patients and should be approached as a systemic disease in which extrahepatic complications increase the weight of its pathological burden.

Myocardial tissue characterization by segmental T2 mapping in thalassaemia major: detecting inflammation beyond iron.

AIMS: We measured myocardial T2 values by a segmental approach in thalassaemia major (TM) patients, comparing such values against T2* values for the detection of myocardial iron overload (MIO), evaluating their potential in detecting subclinical inflammation, and correlating with clinical status. METHODS AND RESULTS: One-hundred and sixty-six patients (102 females, 38.29 ± 11.49years) enrolled in the Extension-Myocardial Iron Overload in Thalassemia Network underwent magnetic resonance imaging for the assessment of hepatic, pancreatic, and cardiac iron overload (T2* technique), of biventricular function (cine images), and of replacement myocardial fibrosis [late gadolinium enhancement (LGE)]. T2 and T2* values were quantified in all 16 myocardial segments, and the global value was the mean of all segments. Global heart T2 values were significantly higher in TM than in a cohort of 80 healthy subjects. T2 and T2* values were significantly correlated. Out of the 25 patients with a decreased global heart T2* value, 11 (44.0%) had reduced T2 values. No patient with a normal T2* value had a decreased T2 value.Eleven (6.6%) patients had a decreased global heart T2 value, 74 (44.6%) a normal global heart T2 value, and 81 (48.8%) an increased global heart T2 value. Biventricular function was comparable amongst the three groups, whilst LGE was significantly more frequent in patients with reduced vs. increased global heart T2 value. Compared with the other two groups, patients with reduced T2 values had significantly higher hepatic and pancreatic iron deposition. CONCLUSION: In TM, T2 mapping does not offer any advantage in terms of sensitivity for MIO assessment but detects subclinical myocardial inflammation.

Pancreatic fatty replacement as risk marker for altered glucose metabolism and cardiac iron and complications in thalassemia major.

OBJECTIVES: This multicenter study assessed the extent of pancreatic fatty replacement and its correlation with demographics, iron overload, glucose metabolism, and cardiac complications in a cohort of well-treated patients with thalassemia major (TM). METHODS: We considered 308 TM patients (median age: 39.79 years; 182 females) consecutively enrolled in the Extension-Myocardial Iron Overload in Thalassemia Network. Magnetic resonance imaging was used to quantify iron overload (IO) and pancreatic fat fraction (FF) by T2* technique, cardiac function by cine images, and to detect replacement myocardial fibrosis by late gadolinium enhancement technique. The glucose metabolism was assessed by the oral glucose tolerance test. RESULTS: Pancreatic FF was associated with age, body mass index, and history of hepatitis C virus infection. Patients with normal glucose metabolism showed a significantly lower pancreatic FF than patients with impaired fasting glucose (p = 0.030), impaired glucose tolerance (p < 0.0001), and diabetes (p < 0.0001). A normal pancreatic FF (< 6.6%) showed a negative predictive value of 100% for abnormal glucose metabolism. A pancreatic FF > 15.33% predicted the presence of abnormal glucose metabolism. Pancreas FF was inversely correlated with global pancreas and heart T2* values. A normal pancreatic FF showed a negative predictive value of 100% for cardiac iron. Pancreatic FF was significantly higher in patients with myocardial fibrosis (p = 0.002). All patients with cardiac complications had fatty replacement, and they showed a significantly higher pancreatic FF than complications-free patients (p = 0.002). CONCLUSION: Pancreatic FF is a risk marker not only for alterations of glucose metabolism, but also for cardiac iron and complications, further supporting the close link between pancreatic and cardiac disease. KEY POINTS: • In thalassemia major, pancreatic fatty replacement by MRI is a frequent clinical entity, predicted by a pancreas T2* < 20.81 ms and associated with a higher risk of alterations in glucose metabolism. • In thalassemia major, pancreatic fatty replacement is a strong risk marker for cardiac iron, replacement fibrosis, and complications, highlighting a deep connection between pancreatic and cardiac impairment.

Development of an HPLC-MS/MS Method for the Determination of Alkaloids in Lupins.

Lupin alkaloids (LAs) represent a class of toxic secondary metabolites in plants, in particular in Lupinus spp.; they are produced as a defense mechanism due to their strong bitter taste and are very dangerous for human and animals. In this work, a sensitive and reliable high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) analytical method for the identification and quantification of thirteen lupin alkaloids was developed and validated according to FDA guidelines. Efficient extraction and clean-up steps, carried out by solid-phase extraction, were finely tuned on the basis of the characteristics of the analytes and lupin samples, providing good selectivity with minimized matrix interference. The effectiveness of the method was proven by the satisfactory recovery values obtained for most of the analytes and a matrix effect ≤23% for all tested levels. In addition, a sensitive and reliable determination of the target compounds was obtained; LOQs were between 1 and 25 µg Kg-1, i.e., below the requested maximum levels (<200 mg Kg-1). The method was applied to evaluate the LAs profile in different batches of raw L. albus L. samples, varying in size and across farming treatments.