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1.
Ann Hematol ; 101(7): 1567-1576, 2022 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-35525883

RESUMEN

Despite advances in the understanding of the pathophysiology of cytomegalovirus (CMV) infection, it remains as one of the most common infectious complications after allogeneic hematopoietic stem cell transplantation (allo-HSCT). The aim of this study was to determine the genotype of cytokines and chemokines in donor and recipient and their association with CMV reactivation. Eighty-five patients receiving an allo-HSCT from an HLA-identical sibling donor were included in the study. Fifty genes were selected for their potential role in the pathogenesis of CMV infection. CMV DNAemia was evaluated until day 180 after allo-HSCT. CMV reactivation was observed in 51/85 (60%) patients. Of the 213 genetic variants selected, 11 polymorphisms in 7 different genes (CXCL12, IL12A, KIR3DL1, TGFB2, TNF, IL1RN, and CD48) were associated with development or protection from CMV reactivation. A predictive model using five of such polymorphisms (CXCL12 rs2839695, IL12A rs7615589, KIR3DL1 rs4554639, TGFB2 rs5781034 for the recipient and CD48 rs2295615 for the donor) together with the development of acute GVHD grade III/IV improved risk stratification of CMV reactivation. In conclusion, the data presented suggest that the screening of five polymorphisms in recipient and donor pre-transplantation could help to predict the individual risk of CMV infection development after HLA-identical allo-HSCT.


Asunto(s)
Infecciones por Citomegalovirus , Trasplante de Células Madre Hematopoyéticas , Citomegalovirus/genética , Infecciones por Citomegalovirus/etiología , Infecciones por Citomegalovirus/genética , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Humanos , Inmunogenética , Estudios Retrospectivos , Trasplante Homólogo/efectos adversos
2.
Biol Blood Marrow Transplant ; 24(7): 1505-1513, 2018 07.
Artículo en Inglés | MEDLINE | ID: mdl-29410295

RESUMEN

Development of de novo hematologic malignancies in donor cells after allogeneic stem cell transplantation (allo-SCT) provides a useful in vivo model to study the process of leukemogenesis. A systematic analysis of the cases reported in the literature was performed to identify risk factors and mechanisms involved in the pathogenesis of donor cell-derived hematologic neoplasms (DCHN) and leukemogenic transformation. Relevant data were extracted from 137 cases. Cases of DCHN show a wide heterogeneity with regard to recipient/donor age, sex mismatch, and conditioning regimen. Some characteristics, such as the type of primary disease, the type of hematologic malignancy of the DCHN, and the stem cell source used in the transplant procedure, differ from those expected. Mechanisms involved in the pathogenesis of DCHN are complex, and several hypotheses have been proposed, such as pre-existing hematologic neoplasms or premalignant clones in the donor, decreased immune surveillance, and damage to bone marrow microenvironment in the recipient. Most likely several if not all these mechanisms play a role in DCHN development. Novel approaches, such as next-generation sequencing to study consecutive samples after allo-SCT in these patients, appear to be promising to decipher the mechanisms of leukemogenesis.


Asunto(s)
Neoplasias Hematológicas/terapia , Trasplante de Células Madre Hematopoyéticas/métodos , Acondicionamiento Pretrasplante/métodos , Adolescente , Adulto , Anciano , Niño , Preescolar , Femenino , Neoplasias Hematológicas/patología , Humanos , Lactante , Recién Nacido , Masculino , Persona de Mediana Edad , Donantes de Tejidos , Adulto Joven
3.
Transplant Cell Ther ; 30(3): 306.e1-306.e12, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38184148

RESUMEN

Chimeric antigen receptor T cells (CAR-T) has emerged as a promising therapy, over 60% of patients fail to sustain a long-term response. The underlying factors that leads to the effectiveness of this therapy are not completely understood, CAR-T cell persistence and monitoring seems to be pivotal for ensuring a successful response. Various monitoring methods such as multiparametric flow cytometry (MFC) or quantitative PCR (qPCR) have been applied. Our objective is to develop digital PCR (dPCR) assays for detection and quantification of CAR-T cells, comparing them with MFC and qPCR. Samples taken at different follow-up times from 45 patients treated with CAR-T therapy were analyzed to assess the correlation between the different methodologies. dPCR presented a high correlation with MFC and qPCR (r = 0.97 and r = 0.87, respectively), while offering a higher sensitivity (0.01%) compared to MFC (0.1%) and qPCR (1%). dPCR emerged as an alternative and highly sensitivity method for monitoring CAR-T cell dynamics. This technique is well-suited for implementation in clinical practice as a complementary technique to MFC.


Asunto(s)
Linfoma de Células B , Receptores Quiméricos de Antígenos , Humanos , Receptores Quiméricos de Antígenos/genética , Inmunoterapia Adoptiva/efectos adversos , Linfoma de Células B/etiología , Linfocitos T , Reacción en Cadena de la Polimerasa
4.
Front Cell Dev Biol ; 12: 1321282, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38505260

RESUMEN

SYNGAP1 haploinsufficiency results in a developmental and epileptic encephalopathy (DEE) causing generalized epilepsies accompanied by a spectrum of neurodevelopmental symptoms. Concerning interictal epileptiform discharges (IEDs) in electroencephalograms (EEG), potential biomarkers have been postulated, including changes in background activity, fixation-off sensitivity (FOS) or eye closure sensitivity (ECS). In this study we clinically evaluate a new cohort of 36 SYNGAP1-DEE individuals. Standardized questionnaires were employed to collect clinical, electroencephalographic and genetic data. We investigated electroencephalographic findings, focusing on the cortical distribution of interictal abnormalities and their changes with age. Among the 36 SYNGAP1-DEE cases 18 presented variants in the SYNGAP1 gene that had never been previously reported. The mean age of diagnosis was 8 years and 8 months, ranging from 2 to 17 years, with 55.9% being male. All subjects had global neurodevelopmental/language delay and behavioral abnormalities; 83.3% had moderate to profound intellectual disability (ID), 91.7% displayed autistic traits, 73% experienced sleep disorders and 86.1% suffered from epileptic seizures, mainly eyelid myoclonia with absences (55.3%). A total of 63 VEEGs were revised, observing a worsening of certain EEG findings with increasing age. A disorganized background was observed in all age ranges, yet this was more common among older cases. The main IEDs were bilateral synchronous and asynchronous posterior discharges, accounting for ≥50% in all age ranges. Generalized alterations with maximum amplitude in the anterior region showed as the second most frequent IED (≥15% in all age ranges) and were also more common with increasing age. Finally, diffuse fast activity was much more prevalent in cases with 6 years or older. To the best of our knowledge, this is the first study to analyze EEG features across different age groups, revealing an increase in interictal abnormalities over infancy and adolescence. Our findings suggest that SYNGAP1 haploinsufficiency has complex effects in human brain development, some of which might unravel at different developmental stages. Furthermore, they highlight the potential of baseline EEG to identify candidate biomarkers and the importance of natural history studies to develop specialized therapies and clinical trials.

5.
Int J Nurs Knowl ; 2023 Sep 12.
Artículo en Inglés | MEDLINE | ID: mdl-37700456

RESUMEN

OBJECTIVE: To identify the most relevant clinical characteristics of the nursing diagnosis frail elderly syndrome (FES) in hospitalized patients aged 65 or older and analyze their impact on 9-month mortality and hospital readmission. METHODS: A prospective and prognostic accuracy study was conducted in patients aged 65 or older, who were admitted to hospital more than 24 h. A consecutive convenience sampling process was used. Assessment included defining characteristics (DCs) of FES, clinical fraility scale (CFS), frail scale (FS), and 9-month mortality and hospital readmission. Statistical tests were used to verify associations between variables. Binary logistic regression analysis and area under the curve were used, to identify significant predictors for the outcomes and evaluate the prognostic accuracy of the DCs. FINDINGS: This study involved 150 patients. CFS scored 65 patients (43.3%, confidence interval 95% 35.2% a 51.6) as frail and proved a prognostic value of mortality at 9 month from pre-frail state (p = 0.020). The mean number of DCs for FES nursing diagnosis was 6.35 (SD = 3.14). Validated tools for measuring frailty were associated with all DCs, excepting nutritional imbalance: below body needs. The hospital readmission during the following 9 months was only statistically related to memory impairment (p = 0.07). CONCLUSION: Clinical frailty scale showed good results as a predictor of mortality. The study suggests exploring including it, in clinical manifestations of elderly frail syndrome. This study found that only memory impairment defining characteristic was predictive of hospital readmission. Further research should identify other relevant and prognostic clinical manifestations. IMPLICATION FOR NURSING PRACTICE: These findings highlight the importance of being vigilant on cognitive decline during hospital admissions. The most prevalent and determinant DCs identified in this study indicate that clinical should focus on preserving functional and mental abilities as well as mobility.

6.
Nurs Open ; 10(9): 5975-5988, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-37452553

RESUMEN

AIMS: To determine adverse effects of ventrogluteal intramuscular injections versus dorsogluteal intramuscular injections. DESIGN: A systematic review and meta-analysis. METHODS: MEDLINE, EMBASE, CINHAL, CENTRAL, LILACS(BVS), BDENF (BVS), WoS, IRCTP(WHO), ClinicalsTrials.gov and PROSPERO databases were searched with no restriction on year or language. Preferred Reporting items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. RESULTS: A total of 1429 participants from 17 studies were included. The meta-analysis found that ventrogluteal injection site had significant relation to lower pain in 9 studies (SMD = -0.63, 95% CI = -0.87, -0.39), bleeding in 4 studies (SMD = -3.46, 95% CI = -6.07, -0.86) and hematoma in 2 studies; after 48 h (SMD = -0.25, 95% CI = -0.39, -0.11), and after 72 h (SMD = -0.16, 95% CI = -0.26, -0.06), if it was compared with dorsogluteal site injection. No differences were found when comparing the possibility of intramuscular injections given into de subcutaneous tissue. In three studies, ventrogluteal site did not significantly reduce the risk of subcutaneous injection (OR 0,62, 95% CI = 0.16, 2.41).


Asunto(s)
Músculo Esquelético , Grasa Subcutánea , Humanos , Inyecciones Intramusculares/efectos adversos , Nalgas , Tejido Subcutáneo
7.
Transplant Cell Ther ; 29(7): 472.e1-472.e4, 2023 07.
Artículo en Inglés | MEDLINE | ID: mdl-36921917

RESUMEN

We propose a novel biomarker that can identify patients at high risk of early progression after chimeric antigen receptor (CAR) T cell therapy. Calculation of cell-free DNA (cfDNA) with a pre-apheresis (PA) and pre-lymphodepletion (PL) sample allows monitoring of tumor dynamics (∆cfDNA). In the present study, ∆cfDNA and other biomarkers and clinical variables were evaluated in 58 patients with relapsed/refractory diffuse large B cell lymphoma (DLBCL). ∆cfDNA (>11 ng/mL plasma; P =.003), C-reactive protein (CRP) PL (>1.06 mg/dL; P = .004), lactate dehydrogenase (LDH) PL (>304; P = .006), disease status PL (progressive disease; P = .035) and sex (male; P = .016) were highly correlated with 1 month progression. After adjusting for ∆cfDNA, CRP PL, and LDH PL, disease status PL, and sex, ∆cfDNA remained associated with 1-month progression after CAR T cell infusion.


Asunto(s)
Ácidos Nucleicos Libres de Células , Linfoma de Células B Grandes Difuso , Receptores Quiméricos de Antígenos , Humanos , Masculino , Receptores Quiméricos de Antígenos/genética , Receptores Quiméricos de Antígenos/uso terapéutico , Ácidos Nucleicos Libres de Células/uso terapéutico , Linfoma de Células B Grandes Difuso/genética , Linfoma de Células B Grandes Difuso/terapia , Inmunoterapia Adoptiva/efectos adversos , Biomarcadores , Tratamiento Basado en Trasplante de Células y Tejidos
8.
Front Immunol ; 13: 1002959, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36211438

RESUMEN

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a curative treatment for patients with hematologic malignances. Haploidentical HSCT (Haplo-HSCT) is an alternative option for patients who do not have an HLA-matched donor. The use of post-transplantation high dose cyclophosphamide (PT-Cy) is commonly employed for graft-versus-host disease (GVHD) prophylaxis in haplo-HSCT. Cyclophosphamide (Cy) is an alkylating agent with antineoplastic and immunosuppressive activity, whose bioactivation requires the activity of polymorphic enzymes in the liver to produce phosphoramide mustard, which is a DNA alkylating agent. To identify polymorphisms in the genes of Cy metabolism and correlate them with post-HSCT complications [GVHD, sinusoidal obstruction syndrome (SOS), hemorrhagic cystitis (HC) and transplant-related mortality (TRM)], we designed a custom next-generation sequencing panel with Cy metabolism enzymes. We analyzed 182 patients treated with haplo-HSCT with PT-Cy from 2007 to 2019, detecting 40 variants in 11 Cy metabolism genes. Polymorphisms in CYP2B6, a major enzyme involved in Cy activation, were associated with decreased activity of this enzyme and a higher risk of Graf-versus-host disease (GVHD). Variants in other activation enzymes (CYP2A6, CYP2C8, CYP2C9, CYP2C19) lead to decreased enzyme activity and were associated with GVHD. Polymorphisms in detoxification genes such as glutathione S-transferases decreased the ability to detoxify cyclophosphamide metabolites due to lower enzyme activity, which leads to increased amounts of toxic metabolites and the development of III-IV acute GVHD. GSMT1*0 a single nucleotide polymorphism previously recognized as a risk factor for SOS was associated with a higher risk of SOS. We conclude that polymorphisms of genes involved in the metabolism of cyclophosphamide in our series are associated with severe grades of GVHD and toxicities (SOS and TRM) after haplo-HSCT and could be used to improve the clinical management of transplanted patients.


Asunto(s)
Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Leucemia Mieloide Aguda , Alquilantes , Ciclofosfamida/efectos adversos , Citocromo P-450 CYP2B6 , Citocromo P-450 CYP2C19 , Citocromo P-450 CYP2C8 , Citocromo P-450 CYP2C9 , ADN , Glutatión , Enfermedad Injerto contra Huésped/genética , Enfermedad Injerto contra Huésped/prevención & control , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Humanos , Leucemia Mieloide Aguda/terapia , Polimorfismo Genético , Transferasas
9.
Cancers (Basel) ; 14(16)2022 Aug 19.
Artículo en Inglés | MEDLINE | ID: mdl-36010999

RESUMEN

FLT3-internal tandem duplication (ITD) analysis is not typically performed in cDNA samples and is not considered an appropriate marker for monitoring measurable residual disease (MRD). The aims of this study were to compare FLT3-ITD mutation analysis in DNA and cDNA samples at diagnosis and to demonstrate the usefulness of its expression measurement as an MRD marker after allogeneic stem cell transplantation (allo-HSCT) or FLT3 inhibitor (FLT3i) administration. A total of 46 DNA and cDNA diagnosis samples, 102 DNA and cDNA post-allo-HSCT samples from 34 patients and 37 cDNA samples from 7 patients with refractory/relapse AML treated with FLT3i were assessed for the FLT3-ITD mutation through fragment analysis. In terms of sensitivity, the analysis of cDNA was superior to that of DNA, quantifying higher allelic ratio values in most cases at diagnosis, and thus optimizing the detection of minor clones and prognostic classification. Regarding the last sample before post-HSCT relapse, cDNA analysis anticipated relapse in most cases, unlike DNA analyses. With regard to the post-FLT3i follow-up, FLT3-ITD expression was reduced after the first FLT3i cycle when the treatment was effective, whereas it was not reduced in refractory patients. FLT3-ITD expression could be a useful additional biomarker at diagnosis and for the assessment of MRD after allo-HSCT and FLT3i in AML.

10.
Leuk Lymphoma ; 62(5): 1178-1186, 2021 05.
Artículo en Inglés | MEDLINE | ID: mdl-33372822

RESUMEN

Although acute myeloid leukemia (AML) with NPM1mut/FLT3-ITDneg is a low-risk entity, its relapse rate remains high. Out of 333 AML patients, 27 were NPM1mut, and were analyzed in greater detail in order to find associations between clinical and molecular features and cumulative incidence of relapse. Next-generation sequencing (NGS) was performed on diagnosis and remission samples using two capture-based panels. The presence of the FLT3D835 variant at diagnosis and a qPCR value of NPM1mut ≥0.1% after induction chemotherapy were associated with an increased probability of relapse, especially if both conditions are present together. By contrast, patients in which the main clone found at diagnosis harbored NPM1 variant had a lower risk of relapse. Nineteen of the 85 variants found at diagnosis were detected by NGS in remission. AML Subgroup with NPM1mut/FLT3-ITDneg is a heterogeneous entity, which can be further risk-stratified based on molecular biomarkers.


Asunto(s)
Leucemia Mieloide Aguda , Proteínas Nucleares , Humanos , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/genética , Mutación , Proteínas Nucleares/genética , Nucleofosmina , Pronóstico , Recurrencia , Riesgo , Tirosina Quinasa 3 Similar a fms/genética
11.
Mol Oncol ; 15(9): 2273-2284, 2021 09.
Artículo en Inglés | MEDLINE | ID: mdl-33533142

RESUMEN

Myeloid neoplasms (MN) with germline predisposition (MNGP) are likely to be more common than currently appreciated. Many of the genes involved in MNGP are also recurrently mutated in sporadic MN. Therefore, routine analysis of gene panels by next-generation sequencing provides an effective approach to detect germline variants with clinical significance in patients with hematological malignancies. Gene panel sequencing was performed in 88 consecutive and five nonconsecutive patients with MN diagnosis. Disease-causing germline mutations in CEBPα, ASXL1, TP53, MPL, GATA2, DDX41, and ETV6 genes were identified in nine patients. Six out of the nine patients with germline variants had a strong family history. These patients presented great heterogeneity in the age of diagnosis and phenotypic characteristics. In our study, there were families in which all the affected members presented the same subtype of disease, whereas members of other families presented various disease phenotypes. This intrafamiliar heterogeneity suggests that the acquisition of particular somatic variants may drive the evolution of the disease. This approach enabled high-throughput detection of MNGP in patients with MN diagnosis, which is of great relevance for both the patients themselves and the asymptomatic mutation carriers within the family. It is crucial to make a proper diagnosis of these patients to provide them with the most suitable treatment, follow-up, and genetic counseling.


Asunto(s)
Predisposición Genética a la Enfermedad , Mutación de Línea Germinal , Neoplasias Hematológicas/diagnóstico , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Cohortes , Femenino , Neoplasias Hematológicas/genética , Humanos , Masculino , Persona de Mediana Edad , Adulto Joven
12.
Front Immunol ; 12: 642087, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33841425

RESUMEN

Haploidentical hematopoietic stem cell transplantation (Haplo-HSCT) with high-dose cyclophosphamide (PTCy) has resulted in a low incidence of graft-vs.-host disease (GVHD), graft failure, and non-relapse mortality. However, post-transplantation relapse remains a common cause of treatment failure in high-risk patients. Unraveling the mechanisms of relapse is therefore crucial for designing effective relapse treatment strategies. One of these mechanisms is the loss of the mismatched HLA on the recipient's leukemic cells. To study the incidence and clinical relevance of this phenomenon, we analyzed 181 patients treated with Haplo-HSCT with PTCy (2007-2019), of which 37 relapsed patients after transplantation. According to the kit employed for HLA-loss analysis, among 22 relapsed patients, we identified HLA loss at relapse in 6 of the 22 patients (27%) studied. Based on the results obtained, the genomic loss of HLA was more common in females than males (66 vs. 33%) and HLA-loss relapses occurred later than classical relapses (345 vs. 166 days). Moreover, the patients with HLA-loss had a greater presence of active disease at the time of transplantation and had undergone a larger number of treatment lines than the group with classical relapses (66 vs. 43% and 66 vs. 18%, respectively). Four of these relapses were studied retrospectively, while two were studied prospectively, the results of which could be considered for patient management. Additionally, two relapsed patients analyzed retrospectively had myeloid neoplasms. One patient had not undergone any treatment, and three had undergone donor lymphocyte infusions (DLIs) and chemotherapy. All presented severe GVHD and disease progression. In contrast, the two patients studied prospectively had a lymphoid neoplasm and were not treated with DLIs. One of them was treated with chemotherapy but died from disease progression, and the other patient underwent a second Haplo-HSCT from a different donor and is still alive. We can conclude that the detection of HLA-loss at the onset of relapse after Haplo-HSCT with PTCy could help in clinical practice to select appropriate rescue treatment, thereby avoiding the use of DLIs or a second transplantation from the same donor.


Asunto(s)
Antígenos HLA/inmunología , Neoplasias Hematológicas/inmunología , Neoplasias Hematológicas/terapia , Trasplante de Células Madre Hematopoyéticas/métodos , Trasplante Haploidéntico/métodos , Adolescente , Adulto , Anciano , Ciclofosfamida/uso terapéutico , Femenino , Humanos , Masculino , Persona de Mediana Edad , Agonistas Mieloablativos/uso terapéutico , Recurrencia Local de Neoplasia/inmunología , Recurrencia , Escape del Tumor/inmunología , Adulto Joven
13.
Sci Rep ; 11(1): 22815, 2021 11 24.
Artículo en Inglés | MEDLINE | ID: mdl-34819573

RESUMEN

Although next-generation sequencing (NGS) data on lymphomas require further validation before being implemented in daily practice, the clinical application of NGS can be considered right around the corner. The aim of our study was to validate an NGS lymphoid panel for tissue and liquid biopsy with the most common types of non-Hodgkin's lymphoma [follicular lymphoma (FL) and diffuse large B-cell lymphoma (DLBCL)]. In this series, 372 somatic alterations were detected in 93.6% (44/47) of the patients through tissue biopsy. In FL, we identified 93 somatic alterations, with a median of 7.4 mutations per sample. In DLBCL, we detected 279 somatic variants with a median of 8.6 mutations (range 0-35). In 92% (24/26) of the cases, we were able to detect some variant in the circulating tumor DNA. We detected a total of 386 variants; 63.7% were detected in both types of samples, 13.2% were detected only in the circulating tumor DNA, and 23% were detected only in the tissue biopsy. We found a correlation between the number of circulating tumor DNA mutations, advanced stage, and bulky disease. The genetic alterations detected in this panel were consistent with those previously described at diagnosis. The liquid biopsy sample is therefore a complementary tool that can provide new genetic information, even in cases where a solid biopsy cannot be performed or an insufficient sample was obtained. In summary, we describe and analyze in this study the findings and difficulties encountered when incorporating liquid biopsy into clinical practice in non-Hodgkin's lymphoma at diagnosis.


Asunto(s)
Biomarcadores de Tumor/genética , Análisis Mutacional de ADN , Secuenciación de Nucleótidos de Alto Rendimiento , Linfoma Folicular/genética , Linfoma de Células B Grandes Difuso/genética , Mutación , Humanos , Biopsia Líquida , Linfoma Folicular/patología , Linfoma de Células B Grandes Difuso/patología , Valor Predictivo de las Pruebas , Reproducibilidad de los Resultados
14.
Cancers (Basel) ; 13(12)2021 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-34203905

RESUMEN

Conventional cytogenetics are the gold standard for the identification of chromosomal alterations recurrent in myeloid neoplasms. Some next-generation sequencing (NGS) panels are designed for the detection of copy number variations (CNV) or translocations; however, their use is far from being widespread. Here we report on the results of a commercial panel including frequent mutations, CNVs and translocations in myeloid neoplasms. Frequent chromosomal alterations were analyzed by NGS in 135 patients with myeloid neoplasms and three with acute lymphoblastic leukemia. NGS analysis was performed using the enrichment-capture Myeloid Neoplasm-GeneSGKit (Sistemas Genómicos, Spain) gene panel including 35 genes for mutational analysis and frequent CNVs and translocations. NGS results were validated with cytogenetics and/or MLPA when possible. A total of 66 frequent alterations included in NGS panel were detected, 48 of them detected by NGS and cytogenetics. Ten of them were observed only by cytogenetics (mainly trisomy 8), and another eight only by NGS (mainly deletion of 12p). Aside from this, 38 secondary CNVs were detected in any of the genes included mainly for mutational analysis. NGS represents a reliable complementary source of information for the analysis of CNVs and translocations. Moreover, NGS could be a useful tool for the detection of alterations not observed by conventional cytogenetics.

15.
Genes (Basel) ; 11(9)2020 08 25.
Artículo en Inglés | MEDLINE | ID: mdl-32854376

RESUMEN

Chimerism refers to the relative proportion of donor and recipient DNA after hematopoietic stem cell transplantation (HSCT) and its quantitative follow-up is of great clinical utility in this setting. PCR of short tandem repeats (STR-PCR) constitutes the gold standard method for chimerism quantification, although more sensitive PCR techniques (such as qPCR) have recently arisen. We compared the sensitivity and the quantification capacity of both techniques in patient samples and artificial mixtures and demonstrated adequate performance of both methods, with higher sensitivity of qPCR and better quantification skills of STR-PCR. By qPCR, we then prospectively followed up 57 patients that were in complete chimerism (CC) by STR-PCR. Twenty-seven patients (59%) showed 0.1-1% recipient DNA in the bone marrow. Only 4 patients presented 0.1-1% recipient DNA in peripheral blood (PB), and one of them relapsed. Finally, by qPCR, we retrospectively studied the last sample that showed CC by STR-PCR prior to relapse in 8 relapsed patients. At a median of 59 days prior to relapse, six patients presented mixed chimerism by qPCR in PB. Since both approaches have complementary characteristics, we conclude that different techniques should be applied in different clinical settings and therefore propose a methodological algorithm for chimerism follow-up after HSCT.


Asunto(s)
Biomarcadores/metabolismo , Repeticiones de Microsatélite/genética , Reacción en Cadena en Tiempo Real de la Polimerasa/métodos , Adolescente , Adulto , Médula Ósea/metabolismo , Niño , Quimerismo , ADN/genética , Femenino , Estudios de Seguimiento , Trasplante de Células Madre Hematopoyéticas/métodos , Humanos , Masculino , Persona de Mediana Edad , Recurrencia , Estudios Retrospectivos , Adulto Joven
16.
Cancers (Basel) ; 11(9)2019 Sep 13.
Artículo en Inglés | MEDLINE | ID: mdl-31540291

RESUMEN

Molecular diagnosis of myeloid neoplasms (MN) is based on the detection of multiple genetic alterations using various techniques. Next-generation sequencing (NGS) has been proved as a useful method for analyzing many genes simultaneously. In this context, we analyzed diagnostic samples from 121 patients affected by MN and ten relapse samples from a subset of acute myeloid leukemia patients using two enrichment-capture NGS gene panels. Pathogenicity classification of variants was enhanced by the development and application of a custom onco-hematology score. A total of 278 pathogenic variants were detected in 84% of patients. For structural alterations, 82% of those identified by cytogenetics were detected by NGS, 25 of 31 copy number variants and three out of three translocations. The detection of variants using NGS changed the diagnosis of seven patients and the prognosis of 15 patients and enabled us to identify 44 suitable candidates for clinical trials. Regarding AML, six of the ten relapsed patients lost or gained variants, comparing with diagnostic samples. In conclusion, the use of NGS panels in MN improves genetic characterization of the disease compared with conventional methods, thus demonstrating its potential clinical utility in routine clinical testing. This approach leads to better-adjusted treatments for each patient.

17.
Enferm. glob ; 21(68): 531-546, Oct. 2022. ilus, tab
Artículo en Español | IBECS (España) | ID: ibc-210016

RESUMEN

Objetivo: analizar las evidencias encontradas en la literatura científica sobre el impacto de las intervenciones psico-educativas en el manejo de la ansiedad, desarrolladas en línea o presenciales con participación de profesionales de enfermería. Método: revisión narrativa e integradora de literatura científica mediante la búsqueda de publicaciones en los principales metabuscadores y en los artículos indexados de las bases de datos de SciELO, MEDLINE y LILACS. Resultados/Discusión: la búsqueda de artículos basados en intervenciones psico-educativas en línea para el manejo de la ansiedad y enfermería, aportó 4.295 publicaciones que, tras las tres etapas de lectura y filtrado, sólo 11 fueron seleccionados: dos revisiones sistemáticas, ocho ECAs y un estudio cuasiexperimental. El aspecto psico-educativo es transversal en cada publicación, siendo efectivo para el manejo de la ansiedad en diversas situaciones clínicas. Aunque hay diversos estudios que evidencian la realización de intervenciones psico-educativas presenciales lideradas por enfermería, no se encontró ningún estudio o investigación específica desarrollada por enfermeras íntegramente en formato on-line. Conclusión: Las modalidades de intervención, estrategias y programas psico-educativos que aprovechan la facilidad de uso e impacto que aporta el uso de las TICs, deben ser valorados desde el ámbito clínico de forma más exhaustiva, ya que estas herramientas facilitan la incorporación de la psico-educación en la rutina clínica. La falta de evidencia sobre la eficacia de estas intervenciones cuando son diseñadas y desarrolladas íntegramente por enfermeras hace necesario plantear investigaciones que evalúen sus resultados. (AU)


Objective: To analyze the evidence found in the scientific literature of the impact of psycho-educational interventions on anxiety management, carried out online or in person with the participation of nursing professionals. Method: Narrative and integrative review of scientific literature by searching for publications in the main metasearch engines and in the indexed articles of the SciELO, MEDLINE and LILACS databases. Results/Discussion: The search for articles based on online psycho-educational interventions for anxiety management and nursing, provided 4,295 publications, of which, after the three stages of reading and filtering, only 11 were selected: two systematic reviews, eight RCTs and one quasi-experimental study. The psycho-educational aspect is transversal in each publication, being effective for the management of anxiety in various clinical situations. Although there are several studies that show the realization of face-to-face psycho-educational interventions led by nursing, we did not find any specific investigation or research carried out by nurses in an entirely online format. Conclusion: The intervention modalities, strategies and psycho-educational programs that take advantage of the ease of use and impact provided using ICT should be evaluated from the perspective of the clinical field in a more exhaustive way, since these tools facilitate the incorporation of psychoeducation into the clinical routine. The lack of evidence on the efficacy of these interventions when they are designed and implemented entirely by nurses makes it necessary to propose research that evaluates the results. (AU)


Asunto(s)
Humanos , Historia del Siglo XXI , Ansiedad , Enfermeras y Enfermeros , Educación , 57970 , Acceso a Internet , Bases de Datos Bibliográficas
18.
Rev Lat Am Enfermagem ; 25: e2915, 2017 07 10.
Artículo en Inglés, Portugués, Español | MEDLINE | ID: mdl-28699998

RESUMEN

Objective: to describe the culture-bound syndromes maintained by Bolivian immigrants in the new migratory context and analyze the care processes of these health problems. Method: qualitative research with an ethnographic methodological approach. Sample: 27 Bolivian immigrants. In-depth interviews and participatory observation were the strategies used for data collection. Data were classified and categorized into logical schemes manually and using the ATLAS-ti program v.5. Results: susto, "wayras", amartelo, pasmo de sol, pasmo de luna and pasmo de sereno are some of the folk illnesses that affect the Bolivian immigrants and that they have to treat in the new migratory context. Conclusions: in the new environment, the group under study preserves culture-bound syndromes that are common in their country of origin. The care strategies used for these health problems are adapted to the resources of the new context and based on interactions with the domestic environment, biomedicine and traditional medicine. It was observed the need for the health professionals to realize that the efficacy of certain therapies occurs within the scope of cultural beliefs and not in that of the scientific evidence.


Asunto(s)
Características Culturales , Emigrantes e Inmigrantes , Enfermería Transcultural , Adulto , Bolivia/etnología , Competencia Cultural , Femenino , Humanos , Masculino , Persona de Mediana Edad , España , Síndrome , Adulto Joven
19.
Enferm Clin ; 27(4): 227-234, 2017.
Artículo en Inglés, Español | MEDLINE | ID: mdl-28400165

RESUMEN

OBJECTIVE: To describe the risk of falls assessments properties and profiles of the patients who fell in a public hospital of the National Health System, and to determine the relationship between the "presence of a fall" and the previous score using the Downton scale, in order to calculate some of the features of this tool: Sensitivity, specificity, positive predictive value, negative predictive value, likelihood ratio, and odss ratio. MATERIALS AND METHODS: A study with a descriptive retrospective design was conducted on the incidence of falls recorded in Cartagena Hospital. An analysis was made of possible causes and effects of falls during the period from March 2010 to March 2015. A total of 576 patients fell during the period of the study, of whom 107 were recorded in the no "fall risk" registry, leaving a sample of 469 patients in the study. Data analysis was performed using the SPSSv.19 Statistics Package. RESULTS: In the context in which the assessment was made, the Downton scale had a sensitivity of 0.58, specificity 0.62, a positive likelihood ratio of 1.55, and negative likelihood ratio of 0.67. The odds ratio calculated was 2.31. CONCLUSIONS: The data on the incidence of falls (0.51%) are similar to those found in other studies. Poor scores obtained on the Downton Index should serve as a wakeup call for the healthcare institutions. An assessment tool that classifies the at-risk patient should be included in patient safety profiles, provided it is of relevant validity to cover any changes in the patient's situation, and acts as a better yardstick than the nurses' own assessment.


Asunto(s)
Accidentes por Caídas/estadística & datos numéricos , Hospitalización , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Medición de Riesgo/métodos , Sensibilidad y Especificidad , Adulto Joven
20.
Cult. cuid ; 23(54): 320-332, mayo-ago. 2019. tab, ilus
Artículo en Español | IBECS (España) | ID: ibc-190434

RESUMEN

OBJETIVO: Describir el "chumpi", una práctica de cuidados a niños de hasta un año de edad propia del ámbito cultural quechua. MÉTODO: Diseño cualitativo basado en el método etnográfico y teoría fundamentada. Muestra: 27 inmigrantes bolivianos. Las estrategias para recoger datos fueron las entrevistas en profundidad y la observación participante. Los datos se categorizaron y ordenaron en esquemas lógicos manualmente y a través del programa ATLAS-ti v.5. RESULTADOS: El chumpi facilita el transporte de los recién nacidos y los protege del frío de la cordillera andina mientras la madre los transporta y trabaja, pero descubrimos que esta práctica se sigue desarrollando por inmigrantes bolivianos en el Sureste de España. Discusión y CONCLUSIONES: Motivaciones relacionadas con la cosmovisión quechua llevan a las mujeres bolivianas a seguir practicando el chumpi en los países a los que emigran. El chumpi moldea el cuerpo y el carácter del lactante de forma que un niño envuelto fuerte será fuerte. El chumpi, una práctica de cuidados, se convierte en una práctica cultural identitaria que puede generar situaciones conflictivas en el ámbito sanitario


OBJECTIVE: To analyze el chumpi, a Quechua baby body care cultural practice during the first year of life. METHOD: Qualitative study based on ethnography and grounded theory procedures. Muestra: 27 inmigrantes bolivianos. Las estrategias para recoger datos fueron las entrevistas en profundidad y la observación participante. Los datos se categorizaron y ordenaron en esquemas lógicos manualmente y a través del programa ATLAS-ti v.5. RESULTS: El chumpi makes newborns transport easier and protects them from the cold of the Andean region while being carried by their working mothers. However, we found that this practice remains among Bolivian immigrants in southeast Spain. CONCLUSIONS: Quechua worldview motivations lead Bolivian women to continue practising el chumpi in destination countries. El chumpi molds the body and the character of the infant so that a strongly wrapped child will be strong. El chumpi, a practice of care, becomes a cultural identity sign. El chumpi generates controversial situations within the health sphere


OBJETIVO: Analisar o chumpi, uma prática cultural de cuidado corporal do bebê Quechua durante o primeiro ano de vida. MÉTODO: Estudo qualitativo baseado em procedimentos de etnografia e teoria fundamentada. Amostra: 27 imigrantes bolivianos. As estratégias para coletar os dados foram entrevistas em profundidade e observação participante. Os dados foram categorizados e ordenados em esquemas lógicos manualmente e através do programa ATLAS-ti v.5. RESULTADOS: O chumpi facilita o transporte de recém-nascidos e protege-os do frio da região andina enquanto são transportados por suas mães trabalhadoras. No entanto, descobrimos que essa prática é mantida entre os imigrantes bolivianos no sudeste da Espanha. CONCLUSÕES: As motivações da visão de mundo quechua levam as mulheres bolivianas a continuar praticando o chumpi nos países de destino. O chumpi molda o corpo e o caráter do bebê, de modo que uma criança bem embrulhada é forte. O chumpi, uma prática de cuidado, torna-se um sinal de identidade cultural. O chumpi gera situações controversas dentro da esfera da saúde


Asunto(s)
Humanos , Masculino , Femenino , Niño , Adulto Joven , Adulto , Persona de Mediana Edad , Emigración e Inmigración , Cuidado del Niño/métodos , Características Culturales , Enfermería Pediátrica , Entrevistas como Asunto , 25783 , Valores Sociales , Bolivia/etnología
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