TM Patients Research Articles

Hematopoietic Stem Cell Transplantation in Children with Sickle Cell Disease and Thalassemia Major: A National Database Study

In patients with sickle cell disease (SCD) and beta-thalassemia major (TM), allogeneic hematopoietic stem cell transplantation (HSCT) was considered the only curative treatment option with a good survival rate. However, with the recent approval of gene therapies, more information is needed to understand the benefits and risks of these interventions. We performed a retrospective analysis of the Kids Inpatient Database to describe demographic features, short-term complications, and hospital charges of patients with SCD and TM treated with HSCT during 2006–2019 in the United States. The database was filtered using the International Classification of Diseases, 9th and 10th edition codes to identify children under 20 years of age with SCD or TM who underwent HSCT. A total of 513 children with SCD or TM who received HSCT were analyzed. The prevalence of HSCT per 1000,000 U.S. population increased from 0.31 in 2006 to 1.99 in 2019 (p < 0.001). The median age of children with SCD who underwent HSCT was 10 (6–15) years, and that for TM was 6 (3–11.5) years (p < 0.001). The combined mortality rate was 4% (2.4%–6.6%) but higher in the TM group. The length-of-stay and total charges were higher in the TM population (p < 0.01). This study provides national data on HSCT among hospitalized children with SCD and TM in the United States, demonstrating an increasing use of HSCT between 2006 and 2019. Although hospital mortality of HSCT in these conditions is low, it still represents a challenge, especially in TM patients.

Cardiac Disease in Egyptian Thalassemia Major and Sickle Cell Disease Adolescents in relation to Vitamin D Status Using Echocardiogram &amp; Ultrafast Magnetic Resonance Imaging

Abstract Background Cardiovascular complications are well recognized in patients with β-thalassemia major (β-TM) and sickle cell disease (SCD). Vitamin D deficiency is prevalent in patients with transfusion-dependent thalassemia and there is an association between vitamin D deficiency and both left ventricular function and iron overload in thalassemia. However, the relationship between vitamin D and cardiac iron is not well studied in Egypt and the role of vitamin D in cardiac disease in SCD and β-TM needs to be assessed. Aim To assess vitamin D status in children and adolescents with SCD and β-TM in relation to cardiac complications using echocardiography and cardiac magnetic resonance (CMR) T2*. Methods Forty-one patients with SCD and 35 patients with β-TM without symptomatic cardiac disease were studied stressing on history of splenectomy and transfusion history. Markers of hemolysis, serum ferritin and vitamin D levels were measured. Liver iron concentration (LIC) was assessed by magnetic resonance imaging (MRI). Screening for cardiovascular abnormalities was performed by the non-invasive Doppler echocardiography and CMR was used to assess myocardial iron overload. Results Echocardiography showed that cardiac functions were significantly impaired in β-TM patients compared with SCD while the frequency of pulmonary hypertension risk (elevated TRV ≥2.5 m/sec) was consistent between both β-TM and SCD groups. Cardiac T2* (which reflects cardiac iron overload) was significantly lower while myocardial iron concentration (MIC) was significantly higher in β -TM patients compared with SCD group. Vitamin D levels were decreased in both SCD and β-TM patients than control levels; however, SCD patients had significantly lower vitamin D levels. Low vitamin D levels were significantly associated withincreased risk of pulmonary hypertension in the SCD group while In β-TM group, vitamin D levels were significantly lower in patients with cardiac disease and those with serum ferritin levels ≥ 2500 µg/L. A significant evidence of diastolic dysfunction was found in SCD and β-TM patients who had low serum vitamin D level &amp;lt; 20 ng/mL. Vitamin D levels were negatively correlated to serum ferritin and LIC while positively correlated to cardiac T2*. Conclusion Low vitamin D levels were associated with cardiopulmonary dysfunction in adolescents with SCD and β-TM. Vitamin D deficiency in those patients was linked to cardiac iron overload leading to iron induced cardiomyopathy. Proper chelation therapy is mandatory to improve cardiac disease, iron overload and consequently, vitamin D status in β-TM patients.

Low Vitamin D Levels Are Associated with Increased Cardiac Iron Uptake in Beta-Thalassemia Major.

We evaluated the association of vitamin D and parathormone (PTH) levels with cardiac iron and function in beta-thalassemia major (β-TM) patients. Two-hundred and seventy-eight TM patients (39.04 ± 8.58 years, 56.8% females) underwent magnetic resonance imaging for the assessment of iron overload (T2* technique), biventricular function parameters (cine images), and replacement myocardial fibrosis (late gadolinium enhancement technique). Vitamin D levels were deficient (<20 ng/dL) in 107 (38.5%) patients, insufficient (20-30 ng/dL) in 96 (34.5%) patients, and sufficient (≥30 ng/dL) in 75 (27.0%) patients. Deficient vitamin D patients had a significantly higher frequency of myocardial iron overload (MIO; global heart T2* < 20 ms) than patients with sufficient and insufficient vitamin D levels and a significantly higher left ventricular end-diastolic volume index and mass index than patients with sufficient vitamin D levels. PTH was not associated with cardiac iron, function, or fibrosis. In the multivariate regression analysis, vitamin D, serum ferritin, and pancreatic iron levels were the strongest predictors of global heart T2* values. In receiver operating characteristic curve analysis, a vitamin D level ≤ 17.3 ng/dL predicted MIO with a sensitivity of 81.5% and a specificity of 75.3% (p < 0.0001). In TM, the periodic and regular assessment of vitamin D levels can be beneficial for the prevention of cardiac iron accumulation and subsequent overt dysfunction.

No-Show Passenger Prediction for Flights

In aviation, “no-show” refers to a customer who booked a reservation but failed to show up. No-shows can result in various resource wastes, such as vacant seats, leading to income loss and flight delays. As a result, no-show passengers can cause considerable problems for airlines, ultimately affecting their bottom line. Recent research has shown the use of machine learning algorithms to reduce the rate of no-shows. For example, a researcher in healthcare is using a predictive model to identify no-shows’ patients to increase efficiency. Therefore, this study aimed to develop prediction models to predict passenger no-shows. In this work, we used a dataset supplied by a local airline company consisting of 1,046,486 rows and 8 columns. Additional datasets like weather data, public holiday data of different countries, aircraft details, and foot traffic data are used to carry out the dataset's feature enrichment task to complement the original dataset. As a result, feature selection has become an important stage in this research to identify and pick the most relevant and useful features from the enormous number of columns. The findings showed that the model built using Random Forest has the highest accuracy of 90.4%, while Decision Tree performed at 90.2%, Gradient Boosting at 86.5%, and Neural Networks at 67.6%. To enhance the accuracy of the models, further research efforts are essential to integrate supplementary passenger information.

The Impacts of Antiretroviral and Antifungal Treatments, and Tuberculosis Co-infection on Mortality and Relapse in Patients with Talaromyces Marneffei Infection

To date, clinical data on long-term clinical outcomes, including 6-month mortality and relapse in talaromycosis (Tm) patients and impacts of ART and secondary antifungal prophylaxis are still lacking. We conducted a secondary data analysis from 6-month prospective observation of patients with culture-confirmed talaromycosis who participated in the Itraconazole versus Amphotericin B for HIV-associated Talaromycosis (IVAP) trial. The primary outcome was 6-month Tm mortality, while the secondary outcome was relapse. Multivariable Cox proportional hazard models were used to identify predictors of outcomes of interest. The median patient age was 34 years (IQR:30 – 38). The median pre-ART CD4 counts at baseline were 10 (IQR: 5-21) cells/µL. The cumulative 76/435 (17.4%) patients died, and Tm relapse was observed in 18/435 (4.1%) patients. The multivariable analyses showed that strong independent predictors of 6-month Tm mortality included ineffective ART (either absence of ART or ART failure) (HR = 6.26, 95% CI: 3.95 – 9.92, P &lt; 0.001), and TB co-infection (HR =1.98, 95% CI: 1.23 – 3.17; P &lt; 0.01). Induction antifungal treatment with itraconazole versus amphotericin B deoxycholate was significantly associated with Tm death in the univariable model, however, it became insignificant in the multivariable model. In addition, the significant risk factors for Tm relapse were ineffective ART, induction antifungal treatment with itraconazole than intravenous amphotericin B, and shorter duration of itraconazole secondary prophylaxis after completing induction therapy in-hospital (all with significant P-values). Antiretroviral therapy, antifungal treatment and tuberculosis co-infection were main predictors for 6-month Tm fatality as well as relapse. Keywords: Invasive fungal infections, Mortality, Relapse, Talaromyces marneffei, Vietnam.

Risk factors for hemorrhagic cystitis in children with β-thalassemia major after allogeneic hematopoietic stem cell transplantation

To explore the risk factors for hemorrhagic cystitis (HC) in children with β-thalassemia major (TM) undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT). A retrospective analysis was conducted on clinical data of 247 children with TM who underwent allo-HSCT at Shenzhen Children's Hospital from January 2021 to November 2022. The children were divided into an HC group (91 cases) and a non-HC group (156 cases) based on whether HC occurred after operation. Multivariable logistic regression analysis was used to explore the risk factors for HC, and the receiver operating characteristic curve was used to analyze the predictive efficacy of related factors for HC. Among the 247 TM patients who underwent allo-HSCT, the incidence of HC was 36.8% (91/247). Univariate analysis showed age, incompatible blood types between donors and recipients, occurrence of acute graft-versus-host disease (aGVHD), positive urine BK virus deoxyribonucleic acid (BKV-DNA), and ≥2 viral infections were associated with the development of HC after allo-HSCT (P<0.05). Multivariable analysis revealed that incompatible blood types between donors and recipients (OR=3.171, 95%CI: 1.538-6.539), occurrence of aGVHD (OR=2.581, 95%CI: 1.125-5.918), and positive urine BKV-DNA (OR=21.878, 95%CI: 9.633-49.687) were independent risk factors for HC in children with TM who underwent allo-HSCT. The receiver operating characteristic curve analysis showed that positive urine BKV-DNA alone or in combination with two other risk factors (occurrence of aGVHD, incompatible blood types between donors and recipients) had a certain accuracy in predicting the development of HC after allo-HSCT (area under the curve >0.8, P<0.05). Incompatible blood types between donors and recipients, occurrence of aGVHD, and positive urine BKV-DNA are risk factors for HC after allo-HSCT in children with TM. Regular monitoring of urine BKV-DNA has a positive significance for early diagnosis and treatment of HC.

The Effect of Iron Overload on the Mobilization of Peripheral Blood Hematopoietic Stem Cells in Pediatric Patients with Thalassemia Major

Introduction: The purpose of this study was to examine the effect of iron overload on the mobilization of peripheral blood stem cells (PBSCs) in pediatric patients with β-thalassemia major (TM). Methods: We retrospectively reviewed the records of 226 patients with TM from whom PBSCs were collected. Iron overload was based on serum ferritin level, and liver and cardiac iron overload was measured by magnetic resonance imaging (MRI) T2*. Results: The mean age of the TM patients was 7.35 ± 3.41 years. Of the patients, only 171 received MRI. Of the 171 patients, 35 had normal liver iron levels, 39 mild liver iron overload, 90 intermediate liver iron overload, and 7 severe liver iron overload. The intermediate + severe group was associated with significantly higher age and BMI and lower leukapheresis product white blood cell count and CD34⁺ cell levels (all, p < 0.05). Conclusion: Leukapheresis indices were similar between patients with different degrees of iron overload according to the ferritin level and cardiac iron overload, in which the later might be due to the small number of patients with cardiac overload. In patients with TM, the intermediate and severe liver iron overload was associated with poorer mobilization of PBSCs.

Evaluation and relation of oral health-related quality of life and oral health status in Thalassemia Major patients, a cross-sectional study

BackgroundBeta-Thalassemia is the most common human inherited disease, directly impacting patients’ physical and psychosocial aspects. The present study evaluated oral health status, oral health-related quality of life (OHRQoL), and their correlation in Thalassemia Major patients.MethodsTwo hundred Thalassemia Major patients aged 12–49 participated in this cross-sectional study. Subjects were selected among the patients referred to the Faculty of Dentistry of Isfahan University of Medical Sciences using simple sampling. Oral Health Impact Profile 14 (OHIP 14) was used to assess OHRQoL. The decayed, Missing, and Filled Teeth (DMFT) index was used as an oral health index. SPSS 22 was used for analysis, using T and Pearson Correlation tests.Results53% of participants were female, and 47% were male. The mean OHIP-14 score (± SD) was 13.20 (± 7.01). The mean DMFT score was 9.54 (± 5.72). DMFT and total OHIP 14 scores correlated significantly (p < 0.001, r = 0.78). All domains of the OHIP-14 score were also significantly correlated with DMFT (p < 0.05).ConclusionsPoor oral health conditions might adversely affect OHRQoL in TM patients. It seems necessary to provide oral treatment needs in order to improve OHRQoL in patients suffering from this particular disease.

Prokineticin 2 and Cytokine Content in the Synovial Fluid of Knee Osteoarthritis and Traumatic Meniscal Tear Patients: Preliminary Results.

Knee osteoarthritis (OA) is a chronic degenerative inflammatory-based condition caused by a cascade of different intra-articular molecules including several cytokines. Among the cytokines, prokineticins (PKs) have recently been identified as important mediators of inflammation and pain. This observational study examined the potential involvement of PK2 in degenerative or traumatic knee disease. Fifteen patients presenting knee osteoarthritis (OA group) and 15 patients presenting a traumatic meniscal tear (TM group) were studied. Synovial fluid samples from affected knees were assessed for PK2, IL-10, and TNF-α using the ELISA method. At a long-term follow-up (minimum 5 years, mean = 6.1 years), patients in the TM group underwent clinical re-evaluation with PROMs (Tegner Activity Scale, IKDC, Lysholm, SKV); in addition, X-ray visualization was used to assess the presence of secondary OA. PK2 was detected in synovial fluids of both TM and OA patients and the levels were comparable between the two groups, while IL-10 levels were significantly greater in the OA group than those in TM patients. PK2 levels correlated with those of IL-10. PK2 levels were greater in blood effusions compared to clear samples, did not differ significantly between sexes, nor were they related to differences in weight, height, or injury (meniscal laterality, time since dosing). No correlation was found between PROMs and radiological classifications in patients in the TM group at final follow-up. These data are the first observations of PK2 in synovial fluid following traumatic meniscus injury. These findings suggest possible further prognostic indices and therapeutic targets to limit the development of secondary OA.

Comparison of thyroid function tests between splenectomised and non-splenectomised β-thalassemia major patients

This study was to evaluate and compare thyroid function tests and serum levels of ferritin in splenectomised and non-splenectomised β-thalassemic patients. This study is a case control study that was conducted in the Thalassemia Center in Ibn Al-Atheer Teaching Hospital in Nineveh Province/ Iraq during March-June 2014. Fifty patients of homozygous β-thalassemia major (TM) and twenty five apparently healthy controls were included in this study. The patients were divided into splenectomised and non-splenectomised patients (each 25 patients). Medical history and blood samples were collected from all participants and serum levels of Thyroid stimulating hormone (TSH), Thyroxine (T4), Free thyroxine (FT4), Triiodothyronie (T3), Free triiodothyronine (FT3), and ferritin in addition to body mass index (BMI) were measured.&#x0D; There were significant decreases in BMI and serum FT4, while there were significant increases in serum TSH and ferritin in β-thalassemia major (in which 10% were diagnosed with hypothyroidism) in comparison with control participants. No significant differences were found between splenectomised and non-splenectomised patients in all parameters measured except a significant positive correlation between serum ferritin and TSH and a significant negative correlation between serum ferritin and T4 that reflects 16% hypothyroidism in splenectomised patients. In addition, significant increases were found in serum TSH and ferritin and a significant decrease in serum FT4 in splenectomised patients when compared with the control. Moreover, a comparison of non-splenectomised patients with control group showed no significant difference in all parameters measured except a significant increase in serum ferritin level. In conclusion, there were certain significant differences in thyroid function tests between β-thalassemia major patients and the controls, whereas there were no significant differences in the means of all studied parameters between splenectomised and non- splenectomised patients except for the positive significant correlation of serum ferritin with TSH level in splenectomised patients which reflect the hypothyroidism in splenectomised TM patients.

Left ventricular global function index is associated with myocardial iron overload and heart failure in thalassemia major patients.

The left ventricular global function index (LVGFI) is a comprehensive marker of cardiac performance, integrating LV morphology with global function. We explored the cross-sectional association of LVGFI with myocardial iron overload (MIO), LV ejection fraction (LVEF), myocardial fibrosis, and heart failure (HF) in β-thalassemia major (TM) patients. We considered 1352 adult TM patients (708 females, 32.79 ± 7.16years) enrolled in the Myocardial Iron Overload in Thalassemia Network and 112 healthy subjects (50 females, 32.09 ± 6.08years). LVGFI and LVEF were assessed by cine images and MIO by multislice multiecho T2* technique. Replacement myocardial fibrosis was detected by late gadolinium enhancement technique. LVGFI and LVEF were significantly lower in patients with significant MIO (global heart T2*<20ms) than in patients without MIO and in healthy subjects but were comparable between TM patients without MIO and healthy subjects. In TM, LVGFI was significantly associated with LVEF (R = 0.733; p < 0.0001). Global heart T2* values were significantly associated with both LVGFI and LVEF, but the correlation with LVGFI was significantly stronger (p = 0.0001). Male sex, diabetes mellitus, significant MIO, and replacement myocardial fibrosis were the strongest predictors of LVGFI. Eighty-six patients had a history of HF and showed significantly lower global heart T2* values, LVEF, and LVGFI than HF-free patients. A LVGFI ≤ 44.9% predicted the presence of HF. The LVGFI showed a diagnostic performance superior to that of LVEF (area under the curve: 0.67 vs. 0.62; p = 0.039). In TM patients the LVGFI correlates with MIO and provides incremental diagnostic value for HF detection compared with LVEF.

Teriparatide in a patient with severe osteoporosis, hypoparathyroidism and thalassemia major

β-Thalassemia Major (TM) is a form of beta-thalassemias. TM complications include, among others, osteoporosis, whose frequency, among TM patients, varies from 13.6% to 50%. The overall etiological mechanisms of TM-related osteoporosis remain unclarified. The primary approach to osteoporosis in patients with TM is the management of TM and its complications and the use of antiresorptive agents, such as Bisphosphonates (BPs), as the first line-drug of treatment. In this article, we present the case of 45 years old-woman with TM and severe osteoporosis, with multiple fractures, albeit the assumption of BPs for many years. The anti-fracture efficacy and safety of BPs are not well-established in TM patients. Data suggest that etidronate and zoledronic acid should be considered as first-line agents in the management of TM- associated osteoporosis. Regarding Teriparatide (TP), there are only a few case reports published about its use in TM patients. It is also noticed that, at the dismission of TP therapy, its benefits are rapidly lost. Finally, regarding romosozumab, our patient presents a significant cardiovascular risk due to the presence of insulin-treated Diabetes Mellitus (DM) and TM-related cardiomyopathy, suggesting we avoid this drug. This case report shows that the therapy of osteoporosis in patients with TM remains an open problem. TM patients often present multiple comorbidities which create limitations to osteoporosis’s treatment. Moreover, these comoboridites are often unavoidable risk factors for osteoporosis.

Cardiopulmonary testing in adult patients with β-thalassemia major in comparison to healthy subjects

β-Thalassemia patients often have a reduced capacity of exercise and abnormal respiratory function parameters, but the reasons are unclear. In order to identify the causes of the exercise limitation, we performed a cardiopulmonary exercise testing (CPET) in a group of 54 adult β-thalassemia major (TM) patients without pulmonary arterial hypertension and in a group of healthy control subjects. All subjects underwent cardiac echocardiography and carried out pulmonary function tests. TM patients also filled an IPAQ questionnaire on usual physical activity (PA).Overall, TM patients have a diminished exercise performance in comparison to control subjects. In fact, peak oxygen uptake (V’O2 peak), expressing maximum exercise capacity, was decreased in 81.5% of the patients; similarly, anaerobic threshold (V’O2@AT) and O2 pulse also resulted lowered. In multivariable regression models adjusted for gender, age, BMI, and mean haemoglobin, V’O2 peak and O2 pulse were positively associated with cardiac iron overload (T2*). No ventilatory limitation to exercise was observed. The most important causes of exercise limitation in these patients were muscular deconditioning and reduced cardiac inotropism due to iron deposition. Only 15/54 (27.8%) TM patients used to perform vigorous physical activity. These results suggest that a program of regular physical activity may be useful to increase the tolerance to effort and therefore to improve the quality of life in these patients.

Efficacy and satisfaction of preoperative telemedicine evaluation of pediatric urologic patients

IntroductionMinimal data exist on the accuracy of preoperative assessment with telemedicine compared to in-person preoperative evaluation. The study compared the efficacy of telemedicine in a clinic or home setting with an in-person approach for pediatric patients with urologic surgical problems.MethodsPreoperative pediatric urologic telemedicine patients between 5 days and 7 years evaluated at our institution were reviewed between January 2011 and June 2020. Both traditional clinic telemedicine patients (TM) and home telemedicine patients (TMH) were included and compared with an in-person (IP) control cohort. Caregivers were invited to complete a National Research Council (NRC) satisfaction phone survey. Data on demographics, preoperative diagnosis/surgical plan, diagnosis at surgery, and surgical procedure were collected.ResultsNinety-six patients with completed surveys were included in the study (34 TM, 24 TMH, and 38 IP). The median age was 10 months TM, 4 months TMH, and 6 months IP. Ethnicity was predominantly non-Hispanic white: 82.4% TM, 91.7% TMH, and 89.5% IP (p = 0.413). Preoperative assessment accuracy was equivalent in the three groups, with 29/34 (85.3%) TM patients, 22/24 (91.7%) TMH patients, and 35/38 (92.1%) IP patients having an accurate surgical plan (p = 0.69). Overall caregiver satisfaction was equivalent (p = 0.231).ConclusionUse of telemedicine for pediatric urological surgical planning may be as effective in accuracy and caregiver satisfaction as in-person evaluation.

Evaluation of coagulation parameters and impact of transfusion on coagulation in patients with beta thalassemia major.

There have been several studies that have shown that patients with beta thalassemia major are at a higher risk of thrombosis due to the procoagulant activity of thalassemic erythrocytes, decreased liver synthetic function, increased platelet activity and vascular endothelial activation attributed to chronic oxidative stress, although there are no established tests to predict thrombotic risk in TM patients. In this study, we evaluated whether or not the platelet function analyser (PFA-200) and thrombin generation test (TGT) would be useful tools to identify hypercoagulability and risk of thrombosis in thalassemia major patients. The study included 50 patients with thalassemia major and 104 healthy control group. Pretransfusion and posttransfusion PFA-200 and TGT results were compared with control group. We found that median C/ADP and C/EPI values in the thalassemia major group were greater in both the pre and posttransfusion samples than the C/ADP and C/EPI results from the control group. The TGT results showed there was no difference between control group and the results from the thalassemia major group. The TGT and PFA-200 testing did not identify hypercoagulability nor identify clear testing parameters to predict a thalassemia major patient's risk of thrombosis. There may be other mechanisms/causes yet unidentified that could better explain thalassemia major patient's increased risk from thromboembolic events.

Beta-thalassaemia major: Prevalence, risk factors and clinical consequences of hypercalciuria.

SummaryRegular transfusion and chelation therapy produces increased life expectancy in thalassaemic patients who may develop new complications. Since few data are available regarding hypercalciuria in β‐thalassaemia major (TM), the aim of our study was to evaluate its prevalence, risk factors and clinical consequences. We enrolled 176 adult TM patients followed at the Center of Thalassemia of Ferrara. Hypercalciuria was defined by a calciuria of 4 mg/kg/day or more in a 24‐h urine sample. Anamnestic, biochemical and radiological data were collected. Hypercalciuria prevalence was reported in 69.3% of patients (females 52.5%). Hypercalciuric (HC) patients used deferasirox (DFX) more often than normocalciuric (NC) patients (47.5% vs 29.6%; p < 0.05). In HC subjects plasma parathyroid hormone (PTH) (24.1 ± 10.4 vs 30.1 ± 13.2 pg/ml) and phosphate levels (3.6 ± 0.5 vs 3.8 ± 0.7 mg/dl) were lower, whereas serum calcium (9.6 ± 0.4 vs 9.4 ± 0.4 mg/dl) and urinary 24‐h phosphaturia (0.9 ± 0.4 vs 0.6 ± 0.3 g/day) were higher as compared to NC patients (p < 0.05 for all comparisons). Supplementation with oral calcium and cholecalciferol was similar between the groups. A higher rate of kidney stones was present in HC (14.8%) versus NC patients (3.7%) (p < 0.05). Hypercalciuria is a frequent complication in adequately treated adult TM patients. Hypercalciuria prevalence is increased in DFX users whereas haemoglobin level or calcium supplements play no role. A significant proportion of HC patients developed kidney stones.

P165 CARDIOVASCULAR RISK FACTORS AND HYPOGONADISM INFLUENCE ON CARDIAC OUTCOMES IN AN AGING POPULATION OF BETA–THALASSEMIA PATIENTS: LOOKING AT THE HEART OF THE PROBLEM

Abstract Background β–thalassemia major (β–TM) is a hereditary genetic disease hindered by many comorbidities due to transfusion–related iron. Despite iron chelation therapy increased the life expectancy up to 50 years today, Iron–related heart disease is still a leading complication, with an expected change in cardiac disease drivers with the ageing of these patients. This study aims to evaluate the distribution and prevalence of cardiovascular risk factors in a population of thalassemia major patients, and their relationship with observed cardiovascular events and potential modifying factors. Methods and Results One–hundred fifty–nine β–TM patients older than 18 years of age were included in this study. Mean age was 40.9 ± 8.4 years. Low serum lipid levels with low HDL levels were noted, with 28% having diabetes mellitus and 62% with hypogonadism; Splenectomy was reported in 70%. During the observed period, 3.8% of patients had at least one episode of heart failure, 35.9% showed early signs of heart failure, 22% received a diagnosis of diastolic dysfunction, 38% had a left ventricular ejection fraction &amp;lt;55%, and 21.4% showed supraventricular arrhythmias. Cardiovascular risk was then assessed using two algorithms (CUORE and Pooled Cohort Risk Equation – PCRE) and was generally low despite the high burden of cardiac–related events. Patients with hypogonadism (who showed lower cardiac T2* value than those without; p &amp;lt; 0.001) showed a statistically significant correlation with the occurrence of cardiovascular events. Discussion The β–TM population has a relatively low mean age, but shows a particular metabolic profile associated with numerous comorbidities: an increased prevalence of diabetes mellitus, low HDL values and frequent hypogonadism, which tends to be associated with increased iron deposition in the myocardium. The cardiovascular risk estimated by specific algorithms (CUORE and PCRE) was generally low, probably due to the young age of the cohort and derivation pitfalls when applied to this specific population, but the prevalence of cardiac events was not negligible. Conclusions The chronic accumulation of iron in the heart and the specific metabolic profile, mainly observed in patients with hypogonadism, allows us to define β–TM as a condition with high cardiovascular risk from many points of view (iron–related myopathy, atherosclerosis and arrhythmias), which requires better stratification tools and specific follow–up program.

Eliminating tattoos for short course palliative radiation therapy: Set-up error, satisfaction and cost

PurposePalliative patients are living longer thanks to advancements in systemic therapies and radiotherapy technologies. Prior to image guided radiotherapy, permanent ink tattoos were used to ensure set up accuracy. Permanent marks can cause psychological damage, physical pain and can reduce a patient’s quality of life. In recent years, image guided radiation therapy (IGRT) has become standard practice and may eliminate the need for permanent tattoos in this patient population. MethodsTwenty-five patients were consecutively chosen from the Palliative Radiation Oncology Program (PROP). Each received 5 fractions of radiotherapy commencing within 72 hours of CT simulation. In place of permanent tattoos, patients were marked with permanent marker and an adherent transparent film dressing (Tegaderm TM ) was placed over the mark. Patients were educated on maintaining the marks and dressing. Daily cone beam CT (CBCT) isocentre mismatch values were compared with 25 patients who received tattoos for radiotherapy to similar body regions. Radiation therapist concerns, cost, variations in isocentre shift values and additional imaging requirements were obtained. ResultsIsocentre shift values were similar (p<0.05) for Tegaderm TM vs. tattoo patients in the anterior-posterior (AP) and right-left (RL) directions. The mean shift value in the superior-inferior (SI) direction was larger for Tegaderm TM than for tattoos (p=0.01), however the magnitude was only 2 mm, which is clinically insignificant as these shifts were prior to IGRT guided correction. No patient required a repeat CBCT or a resimulation. The cost of the Tegaderm TM dressing was substantially less than the tattoo group. Radiation Therapists' satifaction with Tegaderm TM was overall high, however some expressed concerns with their durability and longevity. ConclusionsWe found that the use of Tegaderm TM dressing did not result in increased set-up time, mismatch error or additional imaging procedures (CBCT or CTsimulation) and moreover cost substantially less than permanent ink tattoos.

Humoral immune response to Comirnaty (BNT162b2) SARS-Cov2 mRNA vaccine in Thalassemia Major patients

One of the most urgent needs worldwide is to vaccinate against SARS-CoV-2 as many people as possible. We evaluated humoral response to Comirnaty vaccine in Thalassemia Major patients (TM). We measured SARS-CoV-2–specific antibodies against Spike protein in 57 TM patients and 58 healthy blood donors (HBD). TM and HBD subjects revealed a homogeneous serological response to the Comirnaty (Mean ± SD; TM = 1917,21 ± 1384,49; HBD = 2039,81 ± 1064,44; p = 0,5884). No statistically significant differences were observed among two groups. Interestingly, we observed in 73.3% of asplenic patients Ab-S titres above 800 BAU, whereas only in 26% of non splenectomized patients showed Ab-S titres above 800 BAU). This differences were statistically significant p < 0.039. Further measurement on other Ab types was needed for better understanding humoral response to Comirnaty.

The evolution of glucose-insulin homeostasis in children with β-thalassemia major (β -TM): A twenty-year retrospective ICET- A observational analysis from early childhood to young adulthood.

Background:Thalassemia guidelines recommend oral glucose tolerance test (OGTT), starting from the age of 10 years, or earlier in the presence of iron overload.Objective:The aim of this retrospective study was to review and document the changes of glucose-insulin homeostasis from early childhood to young adulthood in β-thalassemia major (β -TM) patients with impaired fasting glucose (IFG) and normal OGTT.Methods:All data of the clinical patients’ records of 18 β -TM patients from September 1983 to September 2021 were included in the study. Annual or biennial OGTT results, for a duration of 15-20 years, were available for all patients.Results:The main findings are: a) IFG in children with β -TM represents a risk factor for the development of glucose dysregulation (GD) at later age; b) fluctuations of glucose homeostasis during follow-up were observed mainly in β-TM patients with IFG at baseline; and c) the primary defect of GD appears to be a low degree insulin resistance (IR), as estimated by HOMA-IR, followed by an insulin secretion defect.Conclusion:These results are noteworthy as they revealed that firstly, the baseline IFG predicts future development of GD, and secondly, that almost half of patients with IFG at the outset had normal glucose handling 15 years later. Understanding the sequence of abnormalities in the progression from normal glucose homeostasis to GD and identifying the risk factors for the glycometabolic defects in thalassemic patients might help in the formulation of interventions.