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.

Prenatal ultrasound evaluation of fetal Hb Bart's disease among pregnancies at risk at 11 to 14 weeks of gestation.

OBJECTIVE: The objective of this article is to evaluate the efficacy of the first trimester sonomarkers (11-14 weeks) in predicting hemoglobin (Hb) Bart's disease among fetuses at risk MATERIALS AND METHODS: Prospective analysis was conducted on pregnancies at risk of fetal Hb Bart's disease at 11 to 14 weeks of gestation. Sonographic markers including cardiothoracic (CT) ratio, peak systolic velocity of the middle cerebral artery (MCA-PSV), placental thickness, and nuchal translucency were prospectively assessed and recorded. The definite diagnosis of fetal Hb Bart's disease was based on DNA analysis (chorionic villus sampling) or subsequent fetal Hb typing (high-performance liquid chromatography; cordocentesis). RESULTS: Among 104 pregnancies at risk with complete sonographic assessment at 11 to 14 weeks of gestation, 30 fetuses were finally proven to be affected. The CT ratio gave the highest sensitivity, 93.3%, with specificity of 93.2%, followed by placental thickness and MCA-PSV, respectively. Nuchal translucency had a very low sensitivity of 16.7%. The combination of CT ratio and MCA-PSV increased the sensitivity to 96.7% but somewhat compromise specificity. CONCLUSIONS: At 11 to 14 weeks of gestation, sonographic markers can effectively differentiate affected from unaffected pregnancies. The most sensitive marker was CT ratio plus MCA-PSV. Of couples at risk with no any sonographic markers, the risk of having an affected fetus is nearly eliminated.

Misclassification of pulmonary hypertension in adults with sickle hemoglobinopathies using Doppler echocardiography.

OBJECTIVE: To compare the diagnostic utility of Doppler echocardiography-derived tricuspid regurgitant jet velocity (TRV) ≥ 2.5 m/s to right heart catheterization (RHC) in defining pulmonary hypertension (PH) in adult patients with sickle cell disease (SCD). METHODS: This is a retrospective chart review of adults with SCD who had a TRV ≥ 2.5 m/s and RHC. A TRV ≥ 2.5 m/s is suggestive of PH. Pulmonary arterial hypertension (PAH) was defined as a mean pulmonary artery pressure (mPAP) ≥ 25 mm Hg and pulmonary capillary wedge pressure ≤ 15 mm Hg. Pulmonary venous hypertension was defined as an mPAP ≥ 25 mm Hg and pulmonary capillary wedge pressure >15 mm Hg. RESULTS: Twenty-five patients with SCD met the inclusion criteria. Nine of the 25 (36%) patients had an mPAP ≥ 25 mm Hg. Of these 9, 3 (33%) had PAH and 6 (66%) had pulmonary venous hypertension. Patients with PH did not have a higher TRV (3.1 ± 0.68 vs 2.70 ± 0.16 m/s; P = 0.12), but they did have higher cardiac outputs (10.4 ± 2.7 vs 7.81 ± 1.85 L/min; P = 0.012. The specificity of TRV equal to 2.51 m/s in diagnosing PH was 18.8%. At a TRV of 2.88 m/s, the specificity increased to 81%. CONCLUSIONS: In adults with SCD, a TRV of 2.5 m/s lacks specificity for use as a screening tool in the diagnosis of PH. Using a TRV of ≥ 2.88 m/s allows the TRV to be used as a screening tool and reduces the false-positive rate and need for unnecessary RHC.

High fetal splenic artery peak velocity in fetuses with hemoglobin Bart disease: a preliminary study.

OBJECTIVE: The purpose of this study was to evaluate the role of the splenic artery (SPA) peak systolic velocity (PSV) in identifying fetuses with hemoglobin (Hb) Bart disease among pregnancies at risk for the disease. METHODS: Pregnancies at risk for fetal Hb Bart disease scheduled for cordocentesis at 18 to 25 weeks' gestation at Maharaj Nakorn Chiang Mai Hospital were recruited into the study. The SPA PSV was measured before cordocentesis, and the final fetal diagnosis of Hb Bart disease was based on fetal Hb typing using high-performance liquid chromatography. RESULTS: Seventy-six singleton pregnancies at risk for fetal Hb Bart disease were sonographically evaluated for the SPA PSV and underwent cordocentesis for fetal blood analysis. Among the 76 recruited pregnancies, 17 fetuses with Hb Bart disease were finally diagnosed by fetal blood analysis with high-performance liquid chromatography, and the remainder had no abnormalities or had the alpha-thalassemia 1 trait and were defined as unaffected fetuses. The mean SPA PSVs +/- SD for the unaffected and affected fetuses were significantly different: 21.17 +/- 3.7 cm/s (range, 13.8-29.9 cm/s) and 26.12 +/- 3.6 cm/s (range, 20.4-31.5 cm/s) respectively. The SPA PSV of the affected fetuses was higher than that of the unaffected ones (Wilcoxon signed rank test, P < .001). CONCLUSIONS: Splenic artery PSV assessment at mid pregnancy may have a potential role in identifying fetuses with Hb Bart disease. Further studies to evaluate the effectiveness of the SPA PSV in differentiating affected from unaffected fetuses among pregnancies at risk are desirable.

Reappraisal of in utero stem cell transplantation based on long-term results.

The therapeutic field of in utero transplantation of stem cells, into human fetuses, has developed since 1988 with the hope of improved probability of engraftment and tolerance, due to immune immaturity of the host. Fifteen years later, it is possible to evaluate the results that we and others have obtained in the treatment of several fetal diseases. Seven fetal patients have been treated in Lyon: In 2 cases, pregnancy termination was induced by the in utero injection; in the 5 other cases, engraftment was obtained and repeatedly documented with presence of donor HLA antigens and/or Y chromosome in recipients. In the 2 patients with combined immunodeficiency disease, a sustained reconstitution of immunity was obtained as a result of the transplant but other complications occurred thereafter. In patients with thalassemia major, Niemann-Pick disease or hemophilia, a very partial and very transitory benefit was only obtained. Approximately 33 other patients with immunodeficiencies, hemoglobinopathies or inborn errors of metabolism have been treated worldwide, over the last 13 years, with a comparable method, using parental or fetal stem cells transplanted in utero. Successful treatment has usually been recorded in immunodeficiencies, and insufficient results have been obtained in the other cases. This form of treatment can therefore be recommended after prenatal diagnosis of combined immunodeficiency but additional research is required to improve the degree of engraftment, the lack of resistance of the host and the 'space' available for hematopoiesis in the other conditions.

Focal and diffuse increased echogenicity in the renal parenchyma in patients with sickle hemoglobinopathies--an observation.

Eleven patients with sickle hemoglobinopathies undergoing sonographic examinations for reasons unrelated to renal parenchymal disease were incidentally noted to have increased echogenicity in the central portion of the renal parenchyma. This appearance was observed to be a continuum, with some cases showing focally hyperechoic medullary pyramids at one extreme and other cases showing a diffusely echogenic central parenchymal region relative to a thin band of hypoechoic cortical or peripheral parenchyma at the other extreme. The finding of hyperechoic medullae of the kidneys has been reported in patients having conditions associated with hyperuricemia, medullary nephrocalcinosis, or hypokalemia. This sign has not been commonly reported as a finding in patients with sickle syndrome. The thin hypoechoic rim of cortical parenchyma relative to a more echogenic central parenchyma has not been commented on previously.