The coronavirus disease 19 (COVID-19) post pandemic evolution is correlated to the development of new variants. Viral genomic and immune response monitoring are fundamental to the surveillance of ...severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Since 1 January to 31 July 2022, we monitored the SARS-CoV-2 variants trend in Ragusa area sequencing n.600 samples by next generation sequencing (NGS) technology: n.300 were healthcare workers (HCWs) of ASP Ragusa. The evaluation of anti-Nucleocapside (N), receptor-binding domain (RBD), the two subunit of S protein (S1 and S2) IgG levels in 300 exposed vs. 300 unexposed HCWs to SARS-CoV-2 was performed. Differences in immune response and clinical symptoms related to the different variants were investigated. The SARS-CoV-2 variants trend in Ragusa area and in Sicily region were comparable. BA.1 and BA.2 were the most representative variants, whereas the diffusion of BA.3 and BA.4 affected some places of the region. Although no correlation was found between variants and clinical manifestations, anti-N and anti-S2 levels were positively correlated with an increase in the symptoms number. SARS-CoV-2 infection induced a statistically significant enhancement in antibody titers compared to that produced by SARS-CoV-2 vaccine administration. In post-pandemic period, the evaluation of anti-N IgG could be used as an early marker to identify asymptomatic subjects.
Sickle cell disease (SCD) is an inherited red blood cell disorder caused by a structural abnormality of hemoglobin called sickle hemoglobin (HbS). Clinical manifestations of SCD are mainly ...characterized by chronic hemolysis and acute vaso-occlusive crisis, which are responsible for severe acute and chronic organ damage. SCD is widespread in sub-Saharan Africa, in the Middle East, Indian subcontinent, and some Mediterranean regions. With voluntary population migrations, people harboring the HbS gene have spread globally. In 2006, the World Health Organization recognized hemoglobinopathies, including SCD, as a global public health problem and urged national health systems worldwide to design and establish programs for the prevention and management of SCD. Herein we describe the historical experience of the network of hemoglobinopathy centers and their approach to SCD in Italy, a country where hemoglobinopathies have a high prevalence and where SCD, associated with different genotypes including ß-thalassemia, is present in the native population.
Manual erythroexchange (MEEX) was proven to be effective and safe in the management of sickle cell disease (SCD). The goal is to quickly reduce the percentage of hemoglobin S (
HbS
%). A national ...survey of the Italian Society for Thalassemia and Hemoglobinopathies (SITE) observed a great variability among MEEX protocols none of which were found to be predictive of the values of
HbS
% and hemoglobin (
Hb
) after the exchange. Two equations to estimate the
HbS
% and
Hb
values to be obtained after MEEX were developed based on the results of the MEEX procedures in place in the centers participating in the present study. A standard protocol was subsequently defined to evaluate the volumes to exchange to obtain the target values of
HbS
% and
Hb
. The protocol was tested in 261 MEEX performed in SCD patients followed in the 5 participating centers that belong to the Italian Hemoglobinopathy Comprehensive Care Network, with the support of the SITE. The results showed a correlation between the estimated and measured values of
HbS
% and
Hb
(R
p
0.95 and 0.65 respectively,
p
< 0.001). A negligible bias was found for the prediction of
HbS
% and a bias of 1 g/dl for
Hb
. From consecutive MEEX, a rate of increase of
HbS
% between two exchanges of around 0.4% per day (
p
< 0.001) was measured. This protocol was shown to be effective and safe, as all patients reached the target value of
HbS
%. All the MEEX procedures were carried out with single venous access. No adverse events or reactions such as hypotension or electrolyte imbalance were reported nor were any complaints concerning the procedures received from patients.
Sickle cell disease (SCD) is a worldwide distributed hereditary red cell disorder characterized by recurrent acute vaso-occlusive crises (VOCs and anemia). Gold standard treatments are ...hydroxycarbamide (HC) and/or different red blood cell (RBC) transfusion regimens to limit disease progression. Here, we report a retrospective study on 1,579 SCD patients (median age 23 years; 802 males/777 females), referring to 34 comprehensive Italian centers for hemoglobinopathies. Although we observed a similar proportion of Caucasian (47.9%) and African (48.7%) patients, Italian SCD patients clustered into two distinct overall groups: children of African descent and adults of Caucasian descent. We found a subset of SCD patients requiring more intensive therapy with a combination of HC plus chronic transfusion regimen, due to partial failure of HC treatment alone in preventing or reducing sickle cell-related acute manifestations. Notably, we observed a higher use of acute transfusion approaches for SCD patients of African descent when compared to Caucasian subjects. This might be related to (i) age of starting HC treatment; (ii) patients' low social status; (iii) patients' limited access to family practitioners; or (iv) discrimination. In our cohort, alloimmunization was documented in 135 patients (8.5%) and was more common in Caucasians (10.3%) than in Africans (6.6%). Alloimmunization was similar in male and female and more frequent in adults than in children. Our study reinforces the importance of donor-recipient exact matching for ABO, Rhesus, and Kell antigen systems for RBC compatibility as a winning strategy to avoid or limit alloimmunization events that negatively impact the clinical management of SCD-related severe complications.
ClinicalTrials.gov, identifier: NCT03397017.
Objectives
Sickle bone disease (SBD) is a chronic complication of sickle cell disease (SCD) whose pathogenesis is not completely understood. Chronic inflammation associated with SCD could alter bone ...remodeling. Our aim was to analyze the serum levels of bone remodeling markers in a group of SCD children to evaluate their involvement in the SBD.
Methods
We enrolled 26 SCD subjects and 26 age‐matched controls, who lived in the same geographic area. DKK‐1, sclerostin, RANKL, and OPG serum levels were evaluated. Neutrophil‐lymphocyte ratio (NLR) was also evaluated as a marker of inflammation.
Results
The analysis of bone remodeling markers did not show any significant difference between the two groups except for DKK‐1 levels that were significantly higher in the patients than controls (p < .05). A significant direct correlation between NLR and DKK‐1 (p = .004) was found. An inverse correlation between NLR and osteocalcin (p = .01) has also been observed.
Conclusions
The chronic inflammation, which represents a peculiar characteristic in SCD patients, would represent the primary causal agent of the activation of osteoblastogenesis inhibitors responsible of bone impairment in these subjects. Further studies will be needed to better explain the role of these inhibitors in SCD, to prevent or treat bone damage in this population.
Summary
In the last few decades, the life expectancy of regularly transfused β‐thalassaemia major (TM) patients has dramatically improved following the introduction of safe transfusion practices, ...iron chelation therapy, aggressive treatment of infections and improved management of cardiac complications. How such changes, especially those attributed to the introduction of iron chelation therapy, improved the survival of TM patients to approach those with β‐thalassaemia intermedia (TI) remains unknown. Three hundred and seventy‐nine patients with TM (n = 284, dead 40) and TI (n = 95, dead 13) were followed retrospectively since birth until 30 June 2015 or death. Kaplan‐Meir curves showed statistically significant differences in TM and TI survival (P < 0·0001) before the introduction of iron chelation in 1965, which were no longer apparent after that date (P = 0·086), reducing the Hazard Ratio of death in TM compared to TI from 6·8 95% confidence interval (CI) 2·6–17·5 before 1965 to 2·8 (95% CI 0·8–9·2). These findings suggest that, in the era of iron chelation therapy and improved survival for TM, the major‐intermedia dichotomy needs to be revisited alongside future directions in general management and prevention for both conditions.
We conducted the first nation-wide cohort study of sickle cell disease (SCD) in Italy, a Southern European country exposed to intense recent flux migration from endemic areas for SCD. We evaluate the ...impact of hydroxyurea on a total of 652 pediatric and adult patients from 33 Reference Centers for SCD (mean age 24.5±15years, 51.4% males). Hydroxyurea median treatment duration was 7years (range: <1year to 29years) at a mean therapeutic dose of 18±4.7mg/kg/day. Hydroxyurea was associated with a significant increase in mean total and fetal hemoglobin and a significant decrease in mean hemoglobin S, white blood and platelet counts, and lactate dehydrogenase levels. Hydroxyurea was associated with a significant reduction in the incidence of acute chest syndrome (−29.3%, p<0.001), vaso-occlusive crisis (−34.1%, p<0.001), hospitalization (−53.2%, p<0.001), and bone necrosis (−6.9%, p<0.001). New silent cerebral infarction (SCI) occurred during treatment (+42.4%, p<0.001) but not stroke (+0.5%, p=0.572). These observations were generally consistent upon stratification for age, descent (Caucasian or African), genotype (βS/βS, βS/β0 or βS/β+) and duration of treatment (< or ≥10years). There were no new safety concerns observed compared to those commonly reported in the literature. Our study, conducted on a large population of patients with different descent and compound state supports the benefits of hydroxyurea therapy as a treatment option. Registered at clinical trials.gov (NCT02709681).
Summary
The risk of developing hepatocellular carcinoma (HCC) in patients with thalassaemia is increased by transfusion‐transmitted infections and haemosiderosis. All Italian Thalassaemia Centres use ...an ad hoc form to report all diagnoses of HCC to the Italian Registry. Since our last report, in 2002, up to December 2012, 62 new cases were identified, 52% of whom were affected by thalassaemia major (TM) and 45% by thalassaemia intermedia (TI). Two had sickle‐thalassaemia (ST). The incidence of the tumour is increasing, possibly because of the longer survival of patients and consequent longer exposure to the noxious effects of the hepatotropic viruses and iron. Three patients were hepatitis B surface antigen‐positive, 36 patients showed evidence of past infection with hepatitis B virus (HBV). Fifty‐four patients had antibodies against hepatitis C virus (HCV), 43 of whom were HCV RNA positive. Only 4 had no evidence of exposure either to HCV or HBV. The mean liver iron concentration was 8 mg/g dry weight. Therapy included chemoembolization, thermoablation with radiofrequency and surgical excision. Three patients underwent liver transplant, 21 received palliative therapy. As of December 2012, 41 patients had died. The average survival time from HCC detection to death was 11·5 months (1·4–107·2 months). Ultrasonography is recommended every 6 months to enable early diagnosis of HCC, which is crucial to decrease mortality.
▪
Introduction
Sickle cell disease (SCD) is a monogenic, yet highly phenotypically variable disease with multisystem pathology. HbS is prone to polymerization upon deoxygenation, and this property ...underlies all the pathophysiology of SCD. The net result is a chronic hemolytic anemia, with intravascular and extravascular components, and a tendency for microvascular obstruction or vaso-occlusion (VOC). The ability to predict “severe disease” depends on the ability to define it specifically and reproducibly. Many genetic, clinical and laboratory modifiers have been suggested as possible predictors of a “severe disease”. Despite of this wealth of data the modelling of predictor variable continues to be difficult (Quinn et al, 2016).
Considering that the hallmark of SCD is the chronic hemolitic anemia causing increasing of gastro-intestinal iron absorption, our aim was to evaluate if LIC-R2 (Ferriscan) determination may be related with phenotype severity of SCD.
Methods
This was a retrospective study of patients with SCD attending 7 Italian centres participating in the LICNET-S (Liver Iron Cutino NETwork in Sickle Cell Disease), collected at the Campus of Hematology Franco and Piera Cutino, AOOR Villa Sofia-V. Cervello (Palermo, Italy). The LICNET-S protocol was established on June 2018 by Foundation Franco and Piera Cutino of Palermo and approved by our Ethics Committee on 4, July 2018. This analysis included data from LIC-R2 for those patients presenting between July 2018 and July 2019. The MRI-R2 used protocol was that of St Pierre et al, 2005. Retrieved information included laboratory and clinical findings. These are shown as mean±sd and percentages. A linear regression model (LRM) (Draper & Smith, 1998) was used to study the correlation between LIC-R2 and some potential indicators of phenotype severity. All statistical analyses were performed using Stata 12 (StataCorp, College Station, TX, USA).
Results
Overall 65 patients (32 (49.3%) females) whom 16 patients with S/S, 15 with S/beta+ tahalseemia and 34 with S/beta0 thalassemia were enrolled in the study.
Table 1 shows summary of the main clinical findings included in the study to evaluate the LIC-R2 predictivity based on SCD phenotype severity.
Table 2 shows the results of the LRM analysis. The variables statistically significant were the number of the VOC, the Aseptic Avascular Necrosis (AVN) and the Chelation Treatment (CT) (Table 2). However, transfusion regimen was not related with LIC-R2 value, suggesting that chronic hemolitic anemia causing increasing of gastro-intestinal iron absorption rather than transfusion treatment was the main determinant in the LIC-R2 values. This issue is supported by the report of high LIC-R2 in non transfused patients with SCD (Yassim et al, 2017). Table 2 shows even the relationship between the impairment of the single indicator (VOC, AVN, CT) and the LIC-R2 value. All other laboratory and main clinical findings included in Table 2 were not statistically significant. The value of VOC in determining phenotype severity is well known. AVN is a consequence of a chronic ischaemia with inflammatory process evolving at the same time as medullary osteoblastic activity (Mukizi-Musaka et al, 2010). Therefore, it may be related with the chronic hemolitic anemia condition in SCD. Finally, the relationship between CT and LIC-R2 may be explained considering that patients with higher iron body burden are those who received earlier chelation treatment.
Conclusions
This study suggests, as LIC-R2 value is a strong predictive indicator of phenotype severity in SCD. Probably, this is due because of LIC-R2 is related both with acute and chronic hemolitic anemia of SCD causing an increase, during the years, of gastro-intestinal iron absorption.
Therefore, the possibility of preventing VOC, even using new anti-sickling drugs, should be hardly pursued.
Display omitted
No relevant conflicts of interest to declare.
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