RESUMEN
In Europe, multiple waves of infections with SARS-CoV-2 (COVID-19) have been observed. Here, we have investigated whether common patterns of cytokines could be detected in individuals with mild and severe forms of COVID-19 in two pandemic waves, and whether machine learning approach could be useful to identify the best predictors. An increasing trend of multiple cytokines was observed in patients with mild or severe/critical symptoms of COVID-19, compared with healthy volunteers. Linear Discriminant Analysis (LDA) clearly recognized the three groups based on cytokine patterns. Classification and Regression Tree (CART) further indicated that IL-6 discriminated controls and COVID-19 patients, whilst IL-8 defined disease severity. During the second wave of pandemics, a less intense cytokine storm was observed, as compared with the first. IL-6 was the most robust predictor of infection and discriminated moderate COVID-19 patients from healthy controls, regardless of epidemic peak curve. Thus, serum cytokine patterns provide biomarkers useful for COVID-19 diagnosis and prognosis. Further definition of individual cytokines may allow to envision novel therapeutic options and pave the way to set up innovative diagnostic tools.
Asunto(s)
COVID-19/sangre , COVID-19/epidemiología , Citocinas/sangre , Anciano , Biomarcadores/sangre , Prueba de COVID-19 , Estudios de Casos y Controles , Citocinas/metabolismo , Análisis Discriminante , Femenino , Humanos , Interleucina-6/metabolismo , Interleucina-8/metabolismo , Italia/epidemiología , Aprendizaje Automático , Masculino , Persona de Mediana Edad , Pandemias , Análisis de Regresión , SARS-CoV-2RESUMEN
In December 2019, a novel coronavirus, "SARS-CoV-2", was recognized as the cause of coronavirus disease 2019 (COVID-19). Several studies have explored the changes and the role of inflammatory cells and cytokines in the immunopathogenesis of the disease, but until today, the results have been controversial. Based on these premises, we conducted a retrospective assessment of monocyte intracellular TNF-α expression (iTNF-α) and on the frequencies of lymphocyte sub-populations in twenty-five patients with moderate/severe COVID-19. We found lymphopenia in all COVID-19 infected subjects compared to healthy subjects. On initial observation, in patients with favorable outcomes, we detected a high absolute eosinophil count and a high CD4+/CD8+ T lymphocytes ratio, while in the Exitus Group, we observed high neutrophil and CD8+ T lymphocyte counts. During infection, in patients with favorable outcomes, we observed a rise in the lymphocyte count, in the monocyte and in Treg lymphocyte counts, and in the CD4+ and in CD8+ T lymphocytes count but a reduction in the CD4+/CD8+ T lymphocyte ratio. Instead, in the Exitus Group, we observed a reduction in the Treg lymphocyte counts and a decrease in iTNF-α expression. Our preliminary findings point to a modulation of the different cellular mediators of the immune system, which probably play a key role in the outcomes of COVID-19.
Asunto(s)
Tos Ferina/sangre , Tos Ferina/diagnóstico , Tos Ferina/patología , Femenino , Humanos , Recién NacidoRESUMEN
OBJECTIVES: Non-transfusion-dependent thalassemia includes a variety of phenotypes and genotypes that rarely require regular transfusions. However, these patients can experience a wide range of complications. The objective of this retrospective study was to verify whether there is a significant difference in non-transfusion-dependent thalassemia-related complications and treatment among males and females. METHODS: We performed a re-analysis of samples evaluated in a previously published cross-sectional study, regarding 96 non-transfusion-dependent thalassemia patients followed at the 'UOSD Malattie Rare del Globulo Rosso' Centre of the Cardarelli Hospital in Naples, Italy. RESULTS: We found that females were more anemic than males, but there was no significant difference in prevalence of common complications among genders, except for hypogonadism. Furthermore, the transitory regular transfusions regimen in women who had been pregnant does not seem to have a significant impact on overall prognosis. DISCUSSION: In non-transfusion-dependent thalassemia patients, the lower levels of hemoglobin found in females do not seem to indicate a higher prevalence of complications. CONCLUSION: This data should be considered in studies with experimental treatments aiming to correct anemia in patients with non-transfusion-dependent thalassemia. It should probably also be taken into account in order to set up different transfusion regimens among genders in transfusion-dependent patients.
Asunto(s)
Caracteres Sexuales , Talasemia , Adolescente , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Talasemia/sangre , Talasemia/epidemiologíaRESUMEN
We retrospectively evaluated the relationship between serum transferrin receptor-1 (sTfR1) and some fundamental events in the life and the management (the age at diagnosis, the age at the first red blood cells transfusion, the age at splenectomy, and the overall need of chelation therapy) of 111 patients with non-transfusion-dependent thalassemia (NTDT) subdivided in four genetic entities: patients with homozygous or compound heterozygous state for ß-thalassemia, patients with triplicated α genotype associated with ß heterozygosity, patients with deletional HbH, and patients with the combination of a ß defect plus a ß chain variant. We found that the group with homozygous or compound heterozygous state for ß-thalassemia had the highest sTfR1 levels and that the presence of increased sTfR1 levels (>5 times normal) was associated with a complex and severe history of disease requiring splenectomy, occasional red blood cells transfusions, and early start and continuous iron chelation therapy.The complexity in the management of NTDT patients is an emerging issue due to the wide heterogeneity of clinical behavior. Our data indicate that the measurement of sTfR1 levels, a common laboratory test, could contribute to correctly stratify disease history and the iron chelation strategy in NTDT patients.
Asunto(s)
Antígenos CD/sangre , Sobrecarga de Hierro/sangre , Sobrecarga de Hierro/diagnóstico , Receptores de Transferrina/sangre , Talasemia beta/sangre , Adolescente , Adulto , Factores de Edad , Antígenos CD/genética , Niño , Preescolar , Transfusión de Eritrocitos/efectos adversos , Femenino , Humanos , Quelantes del Hierro/administración & dosificación , Sobrecarga de Hierro/tratamiento farmacológico , Sobrecarga de Hierro/genética , Masculino , Persona de Mediana Edad , Receptores de Transferrina/genética , Talasemia beta/genética , Talasemia beta/terapiaRESUMEN
OBJECTIVE: To date in Italy, there is paucity on data about the prevalence, clinical and haematological features of patients carrying the haemoglobin (Hb) Lepore variant in homozygous or in association with other haemoglobinopathies. METHODS: Here we report the results of a retrospective analysis on 33 patients from Campania, a region of Southern Italy, historically followed at 'UOSD Malattie Rare del Globulo Rosso' of Cardarelli hospital, Naples, Italy. RESULTS: We described 33 patients carrying the Hb Lepore variant: 21 compound heterozygotes with a common thalassaemia allele, six patients with homozygous state for Hb Lepore, five patients with Hb Lepore/Hb S and one patient with Hb Lepore/Hb Neapolis were identified. All individuals carried haplotype I or V. DISCUSSION: These thalassaemic patients showed different phenotypes ranging from severe disease with early blood transfusion dependency to moderate form of thalassaemia intermedia. In most cases, thalassaemia mutation type determined the severity of the disease. CONCLUSION: A great variability of clinical phenotype among the same genotypes was also observed suggesting the presence of unknown genetic modifiers acting in combination with Hb Lepore.
Asunto(s)
Hemoglobinopatías/sangre , Hemoglobinopatías/genética , Hemoglobinas Anormales/genética , Hemoglobinas Anormales/metabolismo , Adolescente , Adulto , Alelos , Biomarcadores , Transfusión Sanguínea , Niño , Preescolar , Femenino , Variación Genética , Hemoglobinopatías/diagnóstico , Hemoglobinopatías/terapia , Heterocigoto , Homocigoto , Humanos , Lactante , Italia , Masculino , Persona de Mediana Edad , Mutación , Fenotipo , Estudios Retrospectivos , Adulto JovenRESUMEN
Patients with Non-Transfusion-Dependent Thalassemia may require regular transfusion therapy. However, these patients are at risk of developing irregular antibodies, making them untransfusable. Second line treatment usually includes hydroxyurea, which however is not effective in all patients. Other treatment options include thalidomide, which has been reported to be safe and effective in selected patients. We report the case of a patient who experienced improvement of hemoglobin levels and of a part of NTDT related complications, following 36months of continuous therapy with low doses of thalidomide.
Asunto(s)
Inmunosupresores/uso terapéutico , Talasemia/terapia , Talidomida/uso terapéutico , Antidrepanocíticos/efectos adversos , Transfusión Sanguínea , Médula Ósea/efectos de los fármacos , Médula Ósea/patología , Esquema de Medicación , Femenino , Hemoglobina Fetal/metabolismo , Hemoglobina A2/metabolismo , Humanos , Hidroxiurea/efectos adversos , Isoanticuerpos/biosíntesis , Persona de Mediana Edad , Esplenectomía , Talasemia/sangre , Talasemia/patología , Talasemia/cirugía , Resultado del TratamientoRESUMEN
Complementary medications and herbal medicine for weight loss have become very popular. We report a case of thyroid dysfunction following the ingestion of a kelp-containing marketed diet in a 45-year-old woman with no previous thyroid disease. Signs of hyperthyroidism occurred shortly after a kelp-containing diet. Hyperthyroidism lasted 2â months and was followed by an overt hypothyroidism. The thyroid scintiscan exhibited an extremely low uptake and colour-Doppler ultrasonography revealed multiple small areas of pulsatile flow. After 3â months of levothyroxine substitutive therapy, normal thyroid function was recovered after levothyroxine discontinuation. This clinical history is compatible with a case of iodine-induced thyrotoxicosis followed by prolonged block of the sodium-iodide symporter activity as a consequence of excessive iodine consumption from kelp. Consumers of marketed diets containing kelp or other iodine-rich ingredients should be advised of the risk to develop a thyroid dysfunction also in the absence of underlying thyroid disease.
Asunto(s)
Dieta Reductora/efectos adversos , Hipertiroidismo/inducido químicamente , Hipotiroidismo/inducido químicamente , Yodo/efectos adversos , Kelp , Femenino , Humanos , Hipotiroidismo/tratamiento farmacológico , Persona de Mediana Edad , Glándula Tiroides/diagnóstico por imagen , Tirotoxicosis/inducido químicamente , Tiroxina/uso terapéutico , UltrasonografíaAsunto(s)
Carcinoma de Células Renales/complicaciones , Neoplasias Renales/complicaciones , Talasemia beta/complicaciones , Adulto , Carcinoma de Células Renales/diagnóstico , Carcinoma de Células Renales/terapia , Femenino , Humanos , Neoplasias Renales/diagnóstico , Neoplasias Renales/terapia , Masculino , Resultado del Tratamiento , Talasemia beta/diagnósticoAsunto(s)
Envejecimiento , Deferoxamina/efectos adversos , Quelantes del Hierro/efectos adversos , Riñón/efectos de los fármacos , Nefrolitiasis/inducido químicamente , Reacción a la Transfusión , Talasemia beta/terapia , Adulto , Benzoatos/efectos adversos , Terapia por Quelación/efectos adversos , Deferasirox , Susceptibilidad a Enfermedades , Femenino , Tasa de Filtración Glomerular/efectos de los fármacos , Humanos , Hiperuricemia/etiología , Hiperuricemia/fisiopatología , Hiperuricemia/prevención & control , Incidencia , Sobrecarga de Hierro/etiología , Sobrecarga de Hierro/fisiopatología , Sobrecarga de Hierro/prevención & control , Italia/epidemiología , Riñón/diagnóstico por imagen , Riñón/patología , Riñón/fisiopatología , Masculino , Nefrolitiasis/diagnóstico por imagen , Nefrolitiasis/epidemiología , Nefrolitiasis/etiología , Estudios Retrospectivos , Triazoles/efectos adversos , UltrasonografíaAsunto(s)
Síndrome de Silla Turca Vacía/complicaciones , Hiperprolactinemia/etiología , Neoplasias Hipofisarias/complicaciones , Prolactinoma/complicaciones , Talasemia/complicaciones , Adolescente , Adulto , Anciano , Transfusión Sanguínea , Estudios de Cohortes , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Adulto JovenRESUMEN
BACKGROUND: The mechanisms responsible for the sporadic occurrence of extramedullary haematopoiesis in polytransfused thalassaemic patients have not yet been clarified. In this study we tried to elucidate the influence of genotype and other factors on the presence of extramedullary haematopoiesis. MATERIALS AND METHODS: We performed a retrospective database review of our polytransfused thalassaemic patients between January 2006 and December 2011. Demographic, transfusional, genetic, radiological and biochemical data were collected and statistically analysed. RESULTS: Extramedullary haematopoiesis was found in 18 out of 67 patients (27%). All of them were splenectomised, had a higher nucleated red blood cell count and higher levels of the soluble form of transferrin receptor with respect to patients without extramedullary haematopoiesis; furthermore, patients with EMH had a lower transfusional iron intake and a higher pre-transfusion haemoglobin level as compared with those without extramedullary haematopoiesis. Ten out of the 18 patients with extramedullary haematopoiesis were compound heterozygotes for IVS 1-6/codon 39. A high frequency of thrombotic events was also recorded among all patients followed at our centre with this genetic profile. DISCUSSION: Among our cohort of thalassaemic polytransfused patients, extramedullary haematopoiesis was not such a rare event. Furthermore, we identified a group of patients, most of whom were compound heterozygotes for IVS 1-6/codon 39, with increased soluble transferrin receptor levels and excessive expansion of erythroid marrow probably responsible for the tendency to develop extramedullary haematopoiesis.
Asunto(s)
Hematopoyesis Extramedular , Talasemia beta/fisiopatología , Adolescente , Adulto , Anciano , Cardiomiopatías/epidemiología , Cardiomiopatías/etiología , Femenino , Genotipo , Hemoglobinas/análisis , Heterocigoto , Humanos , Intrones/genética , Sobrecarga de Hierro/epidemiología , Sobrecarga de Hierro/etiología , Italia , Masculino , Persona de Mediana Edad , Receptores de Transferrina/sangre , Estudios Retrospectivos , Esplenectomía , Trombofilia/etiología , Trombofilia/genética , Adulto Joven , Globinas beta/genética , Talasemia beta/genética , Talasemia beta/cirugía , Talasemia beta/terapiaRESUMEN
Few data are available on the prevalence and the risk factors for the presence of kidney stones and hyperuricemia in patients with thalassemia intermedia. We retrospectively reviewed the charts and radiological studies of 89 patients with thalassemia intermedia followed at our clinic with routine biochemical examination and radiological imaging of the urinary tract. Renal calculi were identified in 11 patients (12%) and 22 patients (25%) were under uricosuric treatment for hyperucemia. The prevalence of nephrolithiasis increased with age but not in a statistically significant manner. Major risk factors for renal stone formation were splenectomy (in 91% of the cases) and higher number of erythroblasts. Patients with renal stones had higher mean creatinine level and lower GFR value with respect to those observed in patients not affected. Our data suggest that splenectomy, by further increasing erythrocyte turnover and number, may be directly involved in the pathogenesis of hyperuricemia and nephrolithiasis observed in thalassemia intermedia patients.
Asunto(s)
Hiperuricemia/patología , Cálculos Renales/patología , Talasemia beta/patología , Adolescente , Adulto , Factores de Edad , Anciano , Creatinina/sangre , Eritroblastos/patología , Recuento de Eritrocitos , Eritrocitos/patología , Femenino , Tasa de Filtración Glomerular , Humanos , Hiperuricemia/sangre , Hiperuricemia/etiología , Hiperuricemia/cirugía , Cálculos Renales/sangre , Cálculos Renales/etiología , Cálculos Renales/cirugía , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Riesgo , Esplenectomía , Ácido Úrico/sangre , Talasemia beta/sangre , Talasemia beta/complicaciones , Talasemia beta/cirugíaRESUMEN
In thalassemia intermedia (TI), the increase in bone marrow hemopoietic activity frequently leads to extramedullary erythropoeisis (EMH), but its relationship with the soluble form of transferrin receptor (sTfR) which fully reflects the marrow erythropoietic activity, has not yet been explored. From January 2007 to December 2010, all TI patients attending at our center were prospectively enrolled to undergo sTfR assay and MRI or CT (if claustrophobic) scan evaluation for the presence of paraspinal EMH. A total of 59 patients with TI were studied; EMH involved 23 (39%) patients; overall, the concentration of sTfR varied from 2.6 to 20.6 (mean = 8.7) mg/L, but in splenectomized group and in unsplenectomized group, it varied from 4.2 to 17.8 (mean ± SD = 9.86 ± 3.33) mg/L and from 2.6 to 20.6 (mean ± SD = 7.25 ± 3.9) mg/L, respectively with a statistically significant intergroup difference (p < 0.01). The cutoff point at 8.6 mg/L using the ROC curve showed a sensitivity of 78.3% and a specificity of 72.2%, in predicting EMH but, in unsplenectomized subgroup, they raised to 100% and 90.9%, respectively. These data showed that in TI the level of sTfR could represent a predictive factor of EMH particularly in patients with spleen.
Asunto(s)
Eritropoyesis/fisiología , Hematopoyesis Extramedular/fisiología , Receptores de Transferrina/sangre , Talasemia beta/sangre , Talasemia beta/diagnóstico , Talasemia beta/fisiopatología , Adolescente , Adulto , Anciano , Estudios de Cohortes , Femenino , Humanos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Pronóstico , Estudios Prospectivos , Isoformas de Proteínas/sangre , Receptores de Transferrina/análisis , Receptores de Transferrina/química , Tamaño de la Muestra , Solubilidad , Adulto JovenAsunto(s)
Antivirales/uso terapéutico , Hepacivirus/aislamiento & purificación , Hepatitis C Crónica/tratamiento farmacológico , Hepatitis C Crónica/virología , Interferón-alfa/uso terapéutico , Polietilenglicoles/uso terapéutico , Talasemia/virología , Adulto , Femenino , Humanos , Interferón alfa-2 , Masculino , Proteínas Recombinantes/uso terapéutico , Resultado del TratamientoRESUMEN
In this report, we present a case of a spontaneous pregnancy in a 42-year-old thalassemic woman referred to our Microcythemic Unit while she was on deferasirox (DFX) therapy. The patient had been on treatment with DFX since March 2008 and in March 2009 realized that she was pregnant at 12 weeks of gestation. The conception was spontaneous and the baby was born at full term without complications or malformations.
Asunto(s)
Benzoatos/uso terapéutico , Quelantes del Hierro/uso terapéutico , Complicaciones Hematológicas del Embarazo/tratamiento farmacológico , Triazoles/uso terapéutico , Talasemia beta/tratamiento farmacológico , Administración Oral , Adulto , Benzoatos/administración & dosificación , Deferasirox , Femenino , Humanos , Edad Materna , Embarazo , Resultado del Embarazo , Primer Trimestre del Embarazo , Triazoles/administración & dosificaciónRESUMEN
OBJECTIVE: Although IFN therapy is known to cause neutropenia, data on the risk of deferiprone (DFP)-induced haematological complications in patients receiving IFN are lacking. RESEARCH DESIGN AND METHODS: This was a retrospective single-centre study to assess the association between exposure to IFN for hepatitis C virus treatment and haematological side effects of DFP therapy in patients with thalassemia major and intermedia using a large database spanning 2001 2008. During observation time, a total of 66 patients, including 63 affected by thalassemia major and 3 by thalassemia intermedia, were treated with chelation DFP-based regimens. A subset of 25 patients was treated at least for 3 months also with IFN (6 were cotreated and 19 were pretreated). RESULTS: Overall, the incidence of neutropenia and agranulocytosis was 9.83 and 1.14/100 patient/year, respectively. Receipt of IFN was significantly associated with increased risk of haematological complications of DFP therapy: among patients receiving IFN, 48 and 12% experienced at least one episode of neutropenia and agranulocytosis, respectively. CONCLUSIONS: These results suggest that IFN therapy may increase the risk of complications of DFP-based iron chelation therapy in patients with thalassemia. Further research is needed to assess whether the association observed in this retrospective single-centre observational study is due to IFN or other factors.