RESUMEN
This review aimed to compare the different responses of countries to the pandemic, their National Health Systems, and their impact on citizens' health. This work aimed to create a narrative plot that connects different discussion points and suggests organizational solutions and strategic choices in the face of the pandemic. In particular, this work focused on public health organizations, specifically the European Union and vaccination politics. It is also based on a case report series (about the United States, Germany, Vietnam, New Zealand, Cuba, and Italy), where each country has responded differently to the pandemic in terms of political decisions such as vaccination type, information to citizens, dealings with independent experts, and other specific country factors. In comparing the various models of care systems response to the pandemic, it emerges that: we have found some (few) good practices, but without global coordination, and this is obviously not enough. It is now quite clear that there cannot be a "good answer" in a single nation. Uncoordinated local responses cannot counter a global phenomenon. The second point is that the general context must be considered from a strategic point of view. With the threat of new pandemics (but also of health disasters linked to climate change, pollution, and wars), humanity finds itself at the crossroads between investing in a "democratic" management of international bodies but without power (and at the mercy of the need for funds with consequent conflicts) or in some new leadership proposals that advocate efficiency and problem-solving (and that would probably be able to implement it) but that would place processes totally outside of the public's control.
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COVID-19 , Desastres , Humanos , Pandemias/prevención & control , Investigación , Cambio ClimáticoRESUMEN
PURPOSE: It is well known that interferon-α (IFN-α), used for long time as the main therapy for HCV-related disease, induces thyroid alterations, but the impact of the new direct-acting antivirals (DAAs) on thyroid is not established. Aim of this prospective study was to evaluate if DAAs therapy may induce thyroid alterations. METHODS: A total of 113 HCV patients, subdivided at the time of the enrollment in naïve group (n = 64) and in IFN-α group (n = 49) previously treated with pegylated interferon-α and ribavirin, were evaluated for thyroid function and autoimmunity before and after 20-32 weeks of DAAs. RESULTS: Before starting DAAs, a total of 8/113 (7.1%) patients showed Hashimoto's thyroiditis (HT) all belonging to IFN-α group (8/49, 16.3%), while no HT cases were found in the naïve group. Overall, 7/113 (6.2%) patients were hypothyroid: 3/64 (4.7%) belonging to naïve group and 4/49 (8.2%) to IFN-α group. Furthermore, a total of 8/113 patients (7.1%) showed subclinical hyperthyroidism: 2/64 (3.1%) were from naïve group and 6/49 (12.2%) from IFN-α group. Interestingly, after DAAs therapy, no new cases of HT, hypothyroidism and hyperthyroidism was found in all series, while 6/11 (54.5%) patients with non-autoimmune subclinical thyroid dysfunction became euthyroid. Finally, the only association between viral genotypes and thyroid alterations was genotype 1 and hypothyroidism. CONCLUSIONS: This study supports evidence that DAAs have a limited or missing influence on thyroid in patients with HCV-related diseases. Moreover, it provides preliminary evidence that subclinical non-autoimmune thyroid dysfunction may improve after HCV infection resolution obtained by DAAs.
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Hepatitis C Crónica , Hepatitis C , Hipertiroidismo , Hipotiroidismo , Enfermedades de la Tiroides , Humanos , Antivirales/efectos adversos , Autoinmunidad , Estudios Prospectivos , Hepatitis C Crónica/complicaciones , Hepatitis C Crónica/tratamiento farmacológico , Interferón-alfa/efectos adversos , Hipotiroidismo/tratamiento farmacológico , Hipertiroidismo/tratamiento farmacológico , Hepatitis C/complicaciones , Hepatitis C/tratamiento farmacológicoRESUMEN
Non-classical human leucocyte antigen (HLA)-G class I molecules have an important role in tumor immune escape mechanisms. We investigated HLA-G expression in lymphonode biopsies taken from 8 controls and 20 patients with advanced-stage classical Hodgkin lymphoma (cHL), in relationship to clinical outcomes and the HLA-G 14-basepair (14-bp) deletion-insertion (del-ins) polymorphism. Lymphnode tissue sections were stained using a specific murine monoclonal HLA-G antibody. HLA-G protein expression was higher in cHL patients than controls. In the group of PET-2 positive (positron emission tomography carried out after 2 cycles of standard chemotherapy) patients with a 2-year progression-free survival rate (PFS) of 40%, we observed high HLA-G protein expression within the tumor microenvironment with low expression on Hodgkin and Reed-Sternberg (HRS) cells. Conversely, PET-2 negative patients with a PFS of 86% had higher HLA-G protein expression levels on HRS cells compared to the microenvironment. Lower expression on HRS cells was significantly associated with the HLA-G 14-bp ins/ins genotype. These preliminary data suggest that the immunohistochemical pattern of HLA-G protein expression may represent a useful tool for a tailored therapy in patients with cHL, based on the modulation of HLA-G expression in relation to achievement of negative PET-2.These preliminary data suggest that the immunohistochemical pattern of HLA-G protein expression may represent a useful tool for a tailored therapy in patients with cHL, based on the modulation of HLA-G expression in relation to achievement of negative PET-2.
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Regulación Neoplásica de la Expresión Génica , Genotipo , Antígenos HLA-G/biosíntesis , Enfermedad de Hodgkin/metabolismo , Mutación INDEL , Proteínas de Neoplasias/biosíntesis , Adolescente , Adulto , Femenino , Antígenos HLA-G/genética , Enfermedad de Hodgkin/diagnóstico por imagen , Enfermedad de Hodgkin/genética , Humanos , Masculino , Persona de Mediana Edad , Proteínas de Neoplasias/genética , Tomografía de Emisión de PositronesRESUMEN
Recent insight into the pathophysiology of acute GVHD after allogeneic haematopoietic SCT has led to a growing interest in the role of natural killer (NK) cells. NK cell cytotoxicity is mainly regulated by the interaction of activating and inhibitory killer immunoglobulin-like receptors (KIRs) with their respective ligands. To investigate the impact of KIRs and their ligands on haematopoietic SCT outcome, we performed a retrospective study of 78 transfusion-dependent thalassaemia patients (median age 10 years, range 1-29 years) transplanted from an unrelated donor selected using high-resolution molecular typing for both class I and II loci after a myeloablative conditioning regimen. GVHD prophylaxis consisted of CsA, short-term MTX and anti-thymocyte globulin in all patients. We found that patients transplanted from donors homozygous for KIR haplotype A had a greater risk of developing grade II-IV acute GVHD compared with those transplanted from a donor carrying at least one B haplotype (hazard ratio=4.5, 99% confidence interval=1.2-17.1, P=0.003). Our study suggests that KIR genotyping of donor and recipient pairs could contribute to the identification of patients at high risk for developing severe complications of haematopoietic SCT and thus may help with the choice of intensity of GVHD prophylaxis.
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Trasplante de Células Madre Hematopoyéticas , Receptores KIR/inmunología , Talasemia/cirugía , Adolescente , Adulto , Niño , Preescolar , Femenino , Frecuencia de los Genes , Genotipo , Enfermedad Injerto contra Huésped/inmunología , Haplotipos , Humanos , Lactante , Células Asesinas Naturales/inmunología , Masculino , Receptores KIR/genética , Estudios Retrospectivos , Talasemia/inmunología , Donantes de Tejidos , Resultado del Tratamiento , Adulto JovenAsunto(s)
Antineoplásicos/uso terapéutico , Proteínas de Fusión bcr-abl/genética , Janus Quinasa 2/genética , Leucemia Mielógena Crónica BCR-ABL Positiva/tratamiento farmacológico , Mutación , Piperazinas/uso terapéutico , Pirimidinas/uso terapéutico , Anciano , Benzamidas , Humanos , Mesilato de Imatinib , Leucemia Mielógena Crónica BCR-ABL Positiva/genética , Masculino , Reacción en Cadena de la Polimerasa de Transcriptasa InversaAsunto(s)
Ginecomastia/inducido químicamente , Leucemia Mielógena Crónica BCR-ABL Positiva/tratamiento farmacológico , Inhibidores de Proteínas Quinasas/efectos adversos , Pirimidinas/efectos adversos , Tiazoles/efectos adversos , Anciano , Dasatinib , Ginecomastia/tratamiento farmacológico , Humanos , Masculino , Inhibidores de Proteínas Quinasas/uso terapéutico , Pirimidinas/uso terapéutico , Moduladores Selectivos de los Receptores de Estrógeno/uso terapéutico , Tamoxifeno/uso terapéutico , Tiazoles/uso terapéutico , Resultado del TratamientoRESUMEN
BACKGROUND AND OBJECTIVES: Allogeneic bone marrow transplantation (BMT) is a widely accepted therapeutic approach in homozygous beta-thalassemia. However, the majority of patients do not have a genotypically identical donor within the family. This prompted us to conduct a pilot study to investigate the feasibility of matched unrelated bone marrow transplantation in thalassemia. The major drawback was the high risk of immunologic and transplant-related complications, mainly graft-versus-host disease (GvHD) and graft failure. DESIGN AND METHODS: Our aim was to reduce this risk through careful selection of donor/recipient pairs. HLA haplotypes that show a high linkage disequilibrium among their class I, class II and class III alleles are considered extended or ancestral haplotypes. RESULTS: These haplotypes are conserved and can be shared by apparently unrelated individuals. Our study shows that matching for these haplotypes significantly improves the outcome of unrelated bone marrow transplantation in thalassemia. In fact, results were comparable to those obtained in transplants using HLA-identifical family donors. INTERPRETATION AND CONCLUSIONS: Better results were obtained in patients with lesser iron overload and when the donor shared an identity for the DPB1 alleles.
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Trasplante de Médula Ósea/estadística & datos numéricos , Trasplante Homólogo/estadística & datos numéricos , Talasemia beta/terapia , Adolescente , Adulto , Trasplante de Médula Ósea/inmunología , Niño , Preescolar , Femenino , Prueba de Histocompatibilidad , Humanos , Italia , Masculino , Estudios Retrospectivos , Medición de Riesgo , Resultado del Tratamiento , Talasemia beta/inmunologíaRESUMEN
Beta(0)-thalassaemia intermedia (beta(0)-TI) describes patients who lack beta-globin synthesis yet manifest a non-transfusion-dependent form of beta-thalassaemia. Co-inheritance of alpha-thalassaemia, certain variants of the beta-like globin gene cluster and elevated fetal haemoglobin (HbF) production are all associated with beta(0)-TI. However, the mild phenotypes of many beta(0)-TI patients are unexplained. Genetically determined HbF levels in beta-thalassaemia are difficult to assess because erythrocytes containing HbF (F cells) preferentially survive over erythrocytes without HbF. To evaluate the importance of genetically elevated HbF in beta-thalassaemia, F-cell levels of 19 TI patients' relatives were compared with relatives of transfusion-dependent beta-thalassaemia major patients and those of beta-globin genotype-matched controls. The beta-globin and alpha-globin genotypes, as well as their Ggamma promoter were also examined. Using this approach, in all but one patient the mild phenotype was attributable to either alpha-globin genotype, gamma-globin promoter polymorphism or inherited elevated F-cell levels. The findings of this study establish the F-cell levels required to modify the degree of disease severity significantly and demonstrate that F-cell level is a crucial parameter in the understanding of phenotypic variation in beta-thalassaemia.