Immune response and adverse events after vaccination against SARS-CoV-2 in adult patients with transfusion-dependent thalassaemia.

Patients with transfusion-dependent thalassaemia (TDT) are considered an at increased-risk population for severe and/or morbid coronavirus disease 2019 (COVID-19) infection. Timely vaccination is the main preventive method for severe COVID-19. Different adverse events and reactions after vaccination have been reported, with severe ones being extremely rare. Patients with TDT may have altered immunity due to chronic transfusions, iron overload and chelation therapy, and splenic dysfunction. Here, we show that adult patients with TDT following vaccination with the novel messenger RNA vaccines have mild adverse events and can produce protective antibodies comparable to the healthy population.

Hb Souli, a 6 bp in-frame deletion on the HBA2 gene (HBA2: c.[41-46delCCTGGG]) leads to α-thalassemia intermedia, when in trans to a single α-globin gene deletion.

We report the case of a 5-year-old child with clinical and hematological findings consistent with the diagnosis of α-thalassemia intermedia (α-TI). Molecular analysis disclosed the common 3.7 kb deletion in the α-globin gene cluster in trans to a novel in-frame 6 bp deletion in the HBA2 gene. It removes the sequence CCTGGG (or GCCTGG) that normally encodes for alanine (codon 13) and tryptophan (codon 14). Even though several hemoglobin (Hb) variants with mutations affecting codons 13 or 14 have been described, Hb Souli (HBA2: c.[41-46delCCTGGG]) is, to the best of our knowledge, the first variant to be reported where both amino acid residues, α13Ala and α14Trp, are deleted, leading to unstable and rapidly degraded α-globin chains.

Evaluation of the spline reconstruction technique for PET.

PURPOSE: The spline reconstruction technique (SRT), based on the analytic formula for the inverse Radon transform, has been presented earlier in the literature. In this study, the authors present an improved formulation and numerical implementation of this algorithm and evaluate it in comparison to filtered backprojection (FBP). METHODS: The SRT is based on the numerical evaluation of the Hilbert transform of the sinogram via an approximation in terms of "custom made" cubic splines. By restricting reconstruction only within object pixels and by utilizing certain mathematical symmetries, the authors achieve a reconstruction time comparable to that of FBP. The authors have implemented SRT in STIR and have evaluated this technique using simulated data from a clinical positron emission tomography (PET) system, as well as real data obtained from clinical and preclinical PET scanners. For the simulation studies, the authors have simulated sinograms of a point-source and three digital phantoms. Using these sinograms, the authors have created realizations of Poisson noise at five noise levels. In addition to visual comparisons of the reconstructed images, the authors have determined contrast and bias for different regions of the phantoms as a function of noise level. For the real-data studies, sinograms of an(18)F-FDG injected mouse, a NEMA NU 4-2008 image quality phantom, and a Derenzo phantom have been acquired from a commercial PET system. The authors have determined: (a) coefficient of variations (COV) and contrast from the NEMA phantom, (b) contrast for the various sections of the Derenzo phantom, and (c) line profiles for the Derenzo phantom. Furthermore, the authors have acquired sinograms from a whole-body PET scan of an (18)F-FDG injected cancer patient, using the GE Discovery ST PET/CT system. SRT and FBP reconstructions of the thorax have been visually evaluated. RESULTS: The results indicate an improvement in FWHM and FWTM in both simulated and real point-source studies. In all simulated phantoms, the SRT exhibits higher contrast and lower bias than FBP at all noise levels, by increasing the COV in the reconstructed images. Finally, in real studies, whereas the contrast of the cold chambers are similar for both algorithms, the SRT reconstructed images of the NEMA phantom exhibit slightly higher COV values than those of FBP. In the Derenzo phantom, SRT resolves the 2-mm separated holes slightly better than FBP. The small-animal and human reconstructions via SRT exhibit slightly higher resolution and contrast than the FBP reconstructions. CONCLUSIONS: The SRT provides images of higher resolution, higher contrast, and lower bias than FBP, by increasing slightly the noise in the reconstructed images. Furthermore, it eliminates streak artifacts outside the object boundary. Unlike other analytic algorithms, the reconstruction time of SRT is comparable with that of FBP. The source code for SRT will become available in a future release of STIR.

Plasma neutrophil gelatinase-associated lipocalin levels are markedly increased in patients with non-transfusion-dependent thalassemia: Lack of association with markers of erythropoiesis, iron metabolism and renal function.

BACKGROUND: Neutrophil Gelatinase-Associated Lipocalin (NGAL) (known as NGAL, Lipocalin 2, Siderocalin, Uterocalin, proteinase-3 and 24p3) is a mammalian small 25-kD peptide that belongs to the lipocalin superfamily, which consists of about 20 small lipoproteins. NGAL was initially discovered as an antibacterial factor of natural immunity and an acute-phase protein. NGAL is also an iron trafficking protein, a member of the non-transferrin-bound iron (NTBI) pool and an alternative to the transferrin-mediated iron-delivery pathway. Of note, NTBI, which is elevated in thalassemic patients, induces cellular toxicity. In this study we investigated the possible association of NGAL with parameters of erythropoiesis, iron metabolism and renal injury in patients with non-transfusion-dependent thalassemia (thalassemia intermedia or TI). PATIENTS AND METHODS: Thirty-five patients with TI, 13 men and 22 women, aged 8-63 years, were included in the study, while, 20 healthy individuals served as controls. Plasma NGAL levels were determined using an immunoenzymatic technique. Erythroid marrow activity was estimated by measuring soluble transferrin receptors (sTfR) levels with a turbidimetric technique. NTBI levels were determined using electrothermal atomic absorption spectrometry. Cystatin C, ß2-microglobulin and hs-CRP concentrations were measured by means of immunonephelometric techniques. RESULTS: The main results of the study showed: a) NGAL levels were significantly higher in patients with TI compared to controls (139.1 ± 86.1 vs 51.2 ± 11.8 µg/L, p<0.0001), without significant effect of splenectomy or hydroxyurea on NGAL levels. Only 4 patients had NGAL levels within the control group range, b) no correlation was found between NGAL levels and either the parameters of erythropoiesis Hb, Hb F, reticulocytes and sTfR (p>0.66, p>0.67, p>0.63 and p>0.81 respectively), or with those of iron metabolism ferritin and NTBI (p>0.90 and p>0.95 respectively). CONCLUSIONS: The increased NGAL levels reported for the first time in TI patients in this study are in agreement with the elevated expression of NGAL observed in TI mouse models. We postulate that the induction of NGAL in these patients may represent either a survival response, facilitating the survival of the less damaged thalassemic erythroid precursors, or a consequence of the abnormal iron regulation in TI.