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1.
Chemotherapy ; 68(3): 138-142, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36893739

RESUMEN

INTRODUCTION: Neoangiogenesis has a crucial role in multiple myeloma (MM), and circulating endothelial cells (CECs) contribute to neovascularization by inducing tumor progression and metastasis and by repairing damage to bone marrow vasculature after stem cell transplantation (HSC). We recently proved in a national multicenter study the possibility to reach a high-level standardization in CEC count and analysis based on a polychromatic flow cytometry Lyotube (BD). Our study aimed at assessing the kinetics of CECs in patients with MM undergoing autologous hematopoietic stem cell transplantation (Au-HSCT). METHODS: Blood samples for analysis were collected at different time points before (T0, T1) and after (T2, T3, T4) Au-HSCT. For each sample, 20 × 106 leukocytes were processed as already described (Lanuti 2016 e 2018) through a multistep procedure. CECs were eventually identified as 7-ADDneg/Syto16pos/CD45neg/CD34pos/CD146pos. RESULTS: Twenty-six MM patients were enrolled in the study. Overall, we observed a constant increase of CECs values from T0 to T3 (day of neutrophil engraftment) followed by decrease at T4 (100 days after transplantation). Using the median value of CECs at T3, we could define a cut-off concentration of 618/mL, with patients with more infective complications having CECs above that value (9/13 vs. 2/13; p = 0.005). CONCLUSION: CECs value may be a function of endothelial damage caused by conditioning regimen, as suggested by the increase of their level during the engraftment period. A more severe endothelial damage is reflected by the increase of infective complications in patients with higher CECs value at T3.


Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Mieloma Múltiple , Humanos , Mieloma Múltiple/terapia , Células Endoteliales/patología , Cinética , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Citometría de Flujo/métodos , Trasplante Autólogo
2.
Hum Mol Genet ; 28(7): 1153-1161, 2019 04 01.
Artículo en Inglés | MEDLINE | ID: mdl-30535103

RESUMEN

Elevated serotonin (5-HT) blood levels, the first biomarker identified in autism research, has been consistently found in 20-30% of patients with Autism Spectrum Disorder (ASD). Hyperserotonemia is mainly due to greater 5-HT uptake into platelets, mediated by the 5-HT transporter (SERT) located at the platelet plasma membrane. The protein complex involved in platelet SERT trafficking and externalization includes integrin ß3, the beta subunit of the platelet membrane adhesive GP IIb/IIIa. Integrin ß3 is encoded by the ITGB3 gene, previously identified as a quantitative trait locus (QTL) for 5-HT blood levels in ASD at single nucleotide polymorphism (SNP) rs2317385. The present study aims to identify the functional ITGB3 gene variants contributing to hyperserotonemia. ITGB3 gene sequencing in 20 individuals selected on the basis of rs2317385 genotypes defined four haplotypes encompassing six SNPs located in the ITGB3 gene promoter region, all in linkage disequilibrium with rs2317385. Luciferase assays in two hematopoietic cell lines, K-562 and HEL 92.1.7, demonstrate that ITGB3 gene promoter activity is enhanced by the presence of the C allele at rs55827077 specifically during differentiation into megakaryocytes (P < 0.01), with modulatory effects by flanking SNPs. This same allele is strongly associated with (a) higher 5-HT blood levels in 176 autistic individuals (P < 0.001), (b) greater platelet integrin ß3 protein expression (P < 0.05) and (c) enhanced SERT trafficking from the cytosol toward the platelet plasma membrane (P = 4.05 × 10-11). Our results support rs55827077 as the functional ITGB3 gene promoter variant contributing to elevated 5-HT blood levels in ASD and define a mechanistic chain of events linking ITGB3 to hyperserotonemia.


Asunto(s)
Trastorno del Espectro Autista/genética , Integrina beta3/genética , Proteínas de Transporte de Serotonina en la Membrana Plasmática/fisiología , Adolescente , Adulto , Trastorno Autístico/genética , Niño , Preescolar , Trastornos de Somnolencia Excesiva/genética , Femenino , Predisposición Genética a la Enfermedad/genética , Variación Genética/genética , Genotipo , Haplotipos , Humanos , Integrina beta3/fisiología , Desequilibrio de Ligamiento/genética , Masculino , Polimorfismo de Nucleótido Simple/genética , Regiones Promotoras Genéticas/genética , Transporte de Proteínas/fisiología , Serotonina/análisis , Serotonina/sangre , Serotonina/metabolismo , Proteínas de Transporte de Serotonina en la Membrana Plasmática/genética
3.
Biol Blood Marrow Transplant ; 26(6): 1113-1118, 2020 06.
Artículo en Inglés | MEDLINE | ID: mdl-32068095

RESUMEN

A matched-pair analysis of transplant-related outcomes was carried out in 116 of 255 consecutive patients who received transplants from an HLA identical sibling (n = 58) or haploidentical related donor (n = 58). The 2 patient series were matched with 9 variables: period of transplant, patient and donor age, sex, diagnosis, disease phase, conditioning regimen, donor-recipient sex, and cytomegalovirus (CMV) status combinations. As graft-versus-host disease (GVHD) prophylaxis, all patients received the standard cyclosporine and methotrexate association with the addition of anti-thymocyte globulins, mycophenolate mofetil, and basiliximab in haploidentical, unmanipulated bone marrow recipients. Anti-infectious management, transfusion policy, and supportive care were identical for all patients. By comparing the 2 patient series, no statistically significant difference was observed for the cumulative incidence of advanced acute and extensive chronic GVHD, transplant-related mortality, and relapse. With a median follow-up of 3.5 years, the 5-year disease-free survival was 37% ± 6% and 36% ± 6% for HLA identical sibling and haploidentical recipients, respectively. The results of transplant from HLA identical siblings and haploidentical donors are comparable. Regardless of the HLA matching, other factors known to affect the transplant outcomes, such as donor-recipient age, sex, and CMV status combinations, might drive the search for the best donor.


Asunto(s)
Enfermedad Injerto contra Huésped , Neoplasias Hematológicas , Médula Ósea , Enfermedad Injerto contra Huésped/prevención & control , Neoplasias Hematológicas/terapia , Humanos , Análisis por Apareamiento , Recurrencia Local de Neoplasia , Hermanos
4.
Eur J Cancer Care (Engl) ; 28(6): e13148, 2019 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-31429155

RESUMEN

OBJECTIVES: To identify which factors can influence the patients' perception of protective isolation following Haematopoietic Stem Cell Transplantation (HSCT). METHODS: This is a prospective study conducted in 10 Italian centres, members of the Italian Group of stem cell transplant (GITMO). Patients' perception of protective isolation was assessed using the ISOLA scale between 7 and 9 days post-transplant. Statistical linear regression analysis was performed. RESULTS: The participants were 182 adult patients receiving autologous (48%) or allogeneic (52%) HSCT in protective isolation. Male sex (ß = .152), education level (ß = -.245), double room (ß = .186), satisfaction with visiting hours (ß = -.174) and emotional support from nurses (ß = -.169) were independently associated with isolation-related suffering. Significant predictors of the relationship with oneself included body temperature (ß = -.179), fatigue (ß = -.192) and emotional support from nurses (ß = -.292). Factors independently associated with the relationship with others were education (ß = -.230), chemotherapy cycles (ß = -.218), pain (ß = .150) and satisfaction with visiting hours (ß = -.162). CONCLUSION: Healthcare providers should pay greater attention in caring for those patients who are at risk for a negative isolation experience. Nurses should provide emotional support.


Asunto(s)
Actitud Frente a la Salud , Trasplante de Células Madre Hematopoyéticas/psicología , Aislamiento de Pacientes/psicología , Adulto , Anciano , Femenino , Neoplasias Hematológicas/psicología , Neoplasias Hematológicas/terapia , Humanos , Italia , Modelos Lineales , Masculino , Persona de Mediana Edad , Percepción , Estudios Prospectivos , Encuestas y Cuestionarios , Trasplante Autólogo/psicología , Trasplante Homólogo/psicología , Adulto Joven
5.
Eur J Cancer Care (Engl) ; 28(2): e12955, 2019 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-30357945

RESUMEN

The aim of this study was to develop and psychometrically test a questionnaire assessing patients' perception of protective isolation following haematopoietic stem cell transplantation (HSCT). The conceptual framework for developing the questionnaire was a three-dimensional model that emerged from a metasynthesis: isolation-related suffering, relationship with oneself and relationship with others. Item selection was performed through a focus group, comparison with the findings of two phenomenological studies, and content validity with 22 experts. Cognitive interviews with five patients were used to verify face validity. A validation study was conducted in 10 Italian centres, all members of the Italian Group of stem cell transplant (GITMO). Patients completed the questionnaires between 7 and 9 days post-transplant. Dimensionality was tested through exploratory factor analysis (EFA). A total of 17 items yielded a content validity index (CVI) of 0.88. Participants included 186 adult patients receiving autologous (48%) or allogeneic (52%) HSCT in protective isolation. The EFA yielded a three-factor solution, explaining 55% of the variance. The scale showed adequate psychometric properties, with the exception of three items, which were eliminated. Future studies should test the psychometric properties of the questionnaire through confirmatory factor analysis and verify its transcultural validity.


Asunto(s)
Actitud Frente a la Salud , Trasplante de Células Madre Hematopoyéticas/psicología , Aislamiento de Pacientes/psicología , Encuestas y Cuestionarios , Femenino , Humanos , Masculino , Persona de Mediana Edad , Mieloma Múltiple/psicología , Mieloma Múltiple/terapia , Percepción/fisiología , Estudios Prospectivos , Psicometría
6.
Transfusion ; 57(7): 1734-1743, 2017 07.
Artículo en Inglés | MEDLINE | ID: mdl-28608367

RESUMEN

BACKGROUND: From 2011 to 2014, a total of 71% of the 3834 patients with hematologic malignancies successfully identified a matched unrelated donor (MUD) through the Italian Bone Marrow Donor Registry (IBMDR), corresponding to a transplant efficiency of 62%. STUDY DESIGN AND METHODS: From 2006, the Rome Transplant Network (RTN) followed a hierarchical selection strategy for the alternative donor search: first MUD, second cord blood, and third haploidentical donor. Using a low-resolution HLA, a preliminary query (PQ) was performed in all cases with assignment of good or poor score if more or less than 10 MUDs were identified in Bone Marrow Donors Worldwide. Herein we assessed the utility of PQ and of high-resolution (HR) HLA from the start of the search. Moreover, we compared the donor identification and the transplant efficiency between IBMDR and RTN. RESULTS: At RTN 79% of 417 patients met a good PQ with a 50% MUD identification versus 12.5% with poor PQ. Our policy led to 78 and 74% of alternative donor identification and transplant efficiency, respectively, higher than IBMDR data equal to 71% (p = 0.007) and 62% (p < 0.0001). The timing for donor identification was significantly reduced using HR HLA at the start of the search from 88 to 66 days at IBMDR (p < 0.001) and from 61 to 41 days at RTN (p < 0.001). CONCLUSIONS: Both PQ and HR HLA at the start of the process represents a useful tool to address the search towards the best and timely donor choice. Moreover, establishing a specific donor policy significantly improves the transplant efficiency.


Asunto(s)
Trasplante de Médula Ósea , Neoplasias Hematológicas/terapia , Sistema de Registros , Donante no Emparentado , Adolescente , Adulto , Anciano , Femenino , Prueba de Histocompatibilidad , Humanos , Italia , Masculino , Persona de Mediana Edad , Adulto Joven
7.
Biol Blood Marrow Transplant ; 22(10): 1758-1764, 2016 10.
Artículo en Inglés | MEDLINE | ID: mdl-27349920

RESUMEN

The use of granulocyte colony-stimulating factor (G-CSF) primed bone marrow (G-BM) has been recently considered as an alternative to mobilized hematopoietic stem cells from peripheral blood (G-PB), especially in the haploidentical transplant setting. The purpose of this study was to compare the effect of in vivo G-CSF priming on BM and PB hematopoietic, mesenchymal (MSC), and immune cells. Forty healthy donors undergoing BM harvest for haploidentical transplant were given subcutaneous recombinant human G-CSF for 7 days. BM and PB samples were harvested on days -7 and 0. The hematopoietic stem/progenitor cells increased significantly after G-CSF priming in both BM and PB with a selective rise of BM CD34(+)CD38(-) cell subset. A striking enhancement of the mesenchymal progenitors was detected in G-BM. CD3(+), CD4(+), CD8(+), and CD19(+) cell fractions; the naive CD4(+) and CD8(+) subpopulations; and natural killer and regulatory T cells increased in G-BM, whereas only slight changes were detected in PB. Myeloid dendritic cells (DC1) were significantly up-regulated in both G-BM and G-PB, whereas DC2 increased only in G-BM. In conclusion, our results show substantial differences in the biologic effects exerted by G-CSF at BM and PB levels on hematopoietic cells and immune cell fractions. Furthermore, the impressive rise of MSC progenitors in G-BM might also be relevant to provide MSCs for several clinical use.


Asunto(s)
Médula Ósea/efectos de los fármacos , Factor Estimulante de Colonias de Granulocitos/farmacología , Células Madre de Sangre Periférica/efectos de los fármacos , Donantes de Tejidos , Adulto , Anciano , Células Dendríticas/efectos de los fármacos , Femenino , Voluntarios Sanos , Células Madre Hematopoyéticas/efectos de los fármacos , Humanos , Sistema Inmunológico/citología , Sistema Inmunológico/efectos de los fármacos , Células Asesinas Naturales/efectos de los fármacos , Masculino , Células Madre Mesenquimatosas/efectos de los fármacos , Persona de Mediana Edad , Linfocitos T Reguladores/efectos de los fármacos
8.
Biol Blood Marrow Transplant ; 20(10): 1612-7, 2014 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-24953019

RESUMEN

Hemorrhagic cystitis (HC) occurring after allogeneic transplantation significantly affects quality of life and, in some cases, becomes intractable, increasing the risk of death. To date, its therapy is not established. We used the hemostatic agent fibrin glue (FG) to treat 35 patients with refractory post-transplantation HC. Of 322 adult patients undergoing an allogeneic transplantation for hematological malignancy, 35 developed grade ≥ 2 HC refractory to conventional therapy and were treated with FG, diffusely sprayed on bleeding mucosa by an endoscopic applicator. The cumulative incidence of pain discontinuation and complete remission, defined as regression of all symptoms and absence of hematuria, was 100% at 7 days and 83% ± 7%, respectively, at 50 days from FG application. The 6-month probability of overall survival for all 35 patients and for the 29 in complete remission was 49% ± 8% and 59% ± 9%, respectively. In the matched-pair analysis, the 5-year probability of overall survival for the 35 patients with HC and treated with FG was not statistically different from that of the comparative cohort of 35 patients who did not develop HC (32% ± 9% versus 37% ± 11%, P = not significant). FG therapy is a feasible, effective, repeatable, and affordable procedure for treating grade ≥2 HC after allogeneic transplantation.


Asunto(s)
Cistitis/cirugía , Adhesivo de Tejido de Fibrina/uso terapéutico , Neoplasias Hematológicas/tratamiento farmacológico , Trasplante de Células Madre Hematopoyéticas , Hemorragia/cirugía , Hemostáticos/uso terapéutico , Acondicionamiento Pretrasplante/métodos , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Cistitis/inducido químicamente , Cistitis/inmunología , Cistitis/mortalidad , Cistoscopía , Femenino , Neoplasias Hematológicas/inmunología , Neoplasias Hematológicas/patología , Hemorragia/inducido químicamente , Hemorragia/inmunología , Hemorragia/mortalidad , Humanos , Masculino , Persona de Mediana Edad , Agonistas Mieloablativos/efectos adversos , Análisis de Supervivencia , Trasplante Homólogo
9.
Am J Hematol ; 87(2): 213-7, 2012 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-22076952

RESUMEN

Despite the increased use of intensive immunosuppressive chemo-immunotherapies in patients with lymphoma observed in the last decade, current data on cytomegalovirus (CMV) infection following autologous stem cell transplantation (Auto-SCT) are very limited. To address this peculiar aspect, a retrospective study on a cohort of 128 adult patients consecutively transplanted for lymphoma in three Hematology Institutions was performed with the aim to determine the incidence of and the risk factors for CMV symptomatic infection and/or end-organ disease. Sixteen patients (12.5%) required specific antiviral therapy and 4/16 died (25%); transplant-related mortality (TRM) was significantly influenced by CMV infection (P = 0.005). In univariate analysis, a pre-transplant HBcIgG seropositivity, HBV infection according to clinical-virological definitions, a pre-transplant Rituximab treatment, a diagnosis of B-cell non-Hodgkin lymphoma, and age at transplant were significantly associated with the risk of developing a clinically relevant CMV infection. In multivariate analysis, only a pre-transplant HBcIgG seropositivity (P = 0.008) proved to be an independent predictor of a clinically relevant CMV infection. These results suggest that a pre-transplant HBcIgG seropositivity could be considered as an independent predictor factor of clinically relevant CMV infection after Auto-SCT.


Asunto(s)
Infecciones por Citomegalovirus/diagnóstico , Citomegalovirus , Trasplante de Células Madre Hematopoyéticas , Antígenos del Núcleo de la Hepatitis B/sangre , Enfermedad de Hodgkin/diagnóstico , Linfoma no Hodgkin/diagnóstico , Sistema de Registros , Adolescente , Adulto , Factores de Edad , Anciano , Anticuerpos Monoclonales de Origen Murino/efectos adversos , Antineoplásicos/efectos adversos , Biomarcadores/sangre , Infecciones por Citomegalovirus/tratamiento farmacológico , Infecciones por Citomegalovirus/inmunología , Infecciones por Citomegalovirus/virología , Femenino , Antígenos del Núcleo de la Hepatitis B/inmunología , Enfermedad de Hodgkin/tratamiento farmacológico , Enfermedad de Hodgkin/inmunología , Enfermedad de Hodgkin/virología , Humanos , Linfoma no Hodgkin/tratamiento farmacológico , Linfoma no Hodgkin/inmunología , Linfoma no Hodgkin/virología , Masculino , Persona de Mediana Edad , Pronóstico , Factores de Riesgo , Rituximab , Ciudad de Roma , Trasplante Autólogo
10.
Gene Rep ; 29: 101705, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-36348959

RESUMEN

COVID-19 may be considered a multifactorial disease caused by the interaction between the virus itself, as the environmental contribute, and the genetic background of the host. SARS-CoV-2 infection occurs through the interaction between the spike protein and ACE2, a receptor in the host cells. Clinically, COVID-19 is characterized by a high heterogeneity in symptomatology ranging from asymptomatic to severe symptoms, and even worsening to death. This variability relies on the host genomic profile and other individual comorbidities. We performed exome analysis in one family displaying a variable spectrum of SARS-CoV-2 infection despite a common exposure. After segregation analysis, we found that the c.446C>T p.(S149L) in MAS1 gene was exclusively present in the individual with severe COVID-19, who died because of pneumonia and multiple thrombotic events. MAS1 encodes a receptor for Ang1-7 in the renin-angiotensin system (RAS) with an anti-inflammatory, anti-fibrotic and anti-angiogenic effect. We hypothesize that downregulation of RAS, due to this rare variant, might impair the protective effect and concur to the clinical severity of the disease. Our results support the protective role of the ACE2/Ang-(1-7)/Mas1 axis and the potential danger of its dysregulation leading to severe COVID-19 disease; if further confirmed, these findings will be useful for management of critically ill patients.

11.
PLoS One ; 17(10): e0275988, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36228008

RESUMEN

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection results in a wide range of outcomes characterized by a high heterogeneity in both symptomatology and susceptibility to the disease. In such a perspective, COVID-19 may be considered as a multifactorial disease featured by the interaction between the environment, which is the virus itself, and the genetic profile of the host. Our analysis aimed at investigating the transmission dynamics of SARS-CoV-2 within families whose members responded in different ways to the infection, although the exposure was common to the entire group and occurred before the availability of any vaccine. The goal was to understand how the genetic background of each subject can influence the viral infection outcome and hence the above-mentioned clinical variability. We performed a segregation analysis in 19 Italian families with a designed custom panel of 42 genes involved in immunity and virus entry and which have also been shown to be related to SARS-CoV-2 host response. We carried out both a familial segregation analysis and a global statistical analysis. In the former we identified eighteen risk variants co-segregating with a COVID-positive status and six variants with a possible protective effect. In addition, sixteen variants showed a trend of association to a severe phenotype. Together with common SNPs, we detected private rare variants that may also provide insight into the observed clinical COVID-19 heterogeneity. The global statistical analysis confirmed statistically significant positive associations between SARS-CoV-2 individual response and some specific gene variants identified in familial analysis. In conclusion our data confirm that the clinical expression of COVID-19 is markedly influenced by the host genetic profile both with a mendelian transmission pattern and a polygenic architecture.


Asunto(s)
COVID-19 , Virosis , COVID-19/epidemiología , COVID-19/genética , Humanos , Polimorfismo de Nucleótido Simple , SARS-CoV-2/genética , Internalización del Virus
12.
Epigenomics ; 12(10): 813-823, 2020 05.
Artículo en Inglés | MEDLINE | ID: mdl-32485115

RESUMEN

Aim: To assess promoter methylation levels, gene expression levels and 677C>T/1298A>C genotype and allele frequencies of the MTHFR gene in 45 mothers of attention-deficit/hyperactivity disorder affected child/children (ADHDM) and compare it with age matched healthy control mothers (HCM). Materials & methods: High resolution melting analysis, quantitative real time PCR and PCR-RFLP were performed to assess methylation, gene expression and genotyping, respectively. Significance between ADHDM and HCM was assessed by linear (methylation and gene expression) and logistic regression (genotypes). Results:MTHFR gene expression levels were significantly higher in the ADHDM compared with the HCM group (adj-p < 7.7E-04). No differences in MTHFR promoter methylation level and 677C>T/1298A>C genotype frequencies were detected between ADHDM and HCM. Conclusion: We observed increased MTHFR expression levels not resulting from promoter methylation changes in ADHDM respect to HMC, potentially contributing to the ADHD condition in their children and deserving further investigation.


Asunto(s)
Trastorno por Déficit de Atención con Hiperactividad/genética , Metilación de ADN , Epigénesis Genética , Metilenotetrahidrofolato Reductasa (NADPH2)/genética , Madres , Adulto , Estudios de Casos y Controles , Niño , Femenino , Frecuencia de los Genes , Genotipo , Humanos , Persona de Mediana Edad , Regiones Promotoras Genéticas , Factores de Riesgo , Ciudad de Roma
13.
Arch Plast Surg ; 47(3): 217-222, 2020 May.
Artículo en Inglés | MEDLINE | ID: mdl-32453929

RESUMEN

BACKGROUND: Surgical reconstruction of chronic wounds is often infeasible due to infection, comorbidities, or poor viability of local tissues. The aim of this study was to describe the authors' technique for improving the regenerative and antimicrobial potential of a combination of modified nanofat and platelet-rich plasma (PRP) in nonhealing infected wounds. METHODS: Fourteen patients met the inclusion criteria. Fat tissue was harvested from the lower abdomen following infiltration of a solution of 1,000 mL of NaCl solution, 225 mg of ropivacaine, and 1 mg of epinephrine. Aspiration was performed using a 3-mm cannula with 1-mm holes. The obtained solution was decanted and mechanically emulsified, but was not filtered. Non-activated leukocyte-rich PRP (naLR-PRP) was added to the solution before injection. Patients underwent three sessions of injection of 8-mL naLR-PRP performed at 2-week intervals. RESULTS: Thirteen of 14 patients completed the follow-up. Complete healing was achieved in seven patients (53.8%). Four patients (30.8%) showed improvement, with a mean ulcer width reduction of 57.5%±13.8%. Clinical improvements in perilesional skin quality were reported in all patients, with reduced erythema, increased thickness, and increased pliability. An overall wound depth reduction of 76.6%±40.8% was found. Pain was fully alleviated in all patients who underwent re-epithelization. A mean pain reduction of 42%±33.3% (as indicated by visual analog scale score) was found in non-re-epithelized patients at a 3-month follow-up. CONCLUSIONS: The discussed technique facilitated improvement of both the regenerative and the antimicrobial potential of fat grafting. It proved effective in surgically-untreatable infected chronic wounds unresponsive to conventional therapies.

14.
Transfusion ; 49(1): 170-5, 2009 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-18954405

RESUMEN

BACKGROUND: Patients undergoing hematopoietic stem cell transplant (HSCT) are particularly exposed to the risk of developing hemorrhagic cystitis (HC), which is characterized by symptoms ranging from macroscopic hematuria to renal failure. Although HC significantly affects the quality of life and in a few cases becomes intractable leading to patient death, its therapeutic management has not been established. Fibrin glue (FG), a hemostatic agent derived from human plasma, has been largely employed in different surgical settings including urologic procedures. STUDY DESIGN AND METHODS: In this pilot study we used FG to treat refractory HC. During cystoscopy, bladder distension was maintained at a constant pressure of 12 mmHg by a carbon dioxide insufflator. An endoscopic applicator allowed spraying FG on the bleeding and raw surfaces of bladder mucosa. RESULTS: Five of 221 patients undergoing an HSCT developed a very severe, refractory HC and have been treated with endoscopic FG. The treatment was successful in 3 patients; the response was partial in 1 patient and transient in the last one, whose clinical course was severely complicated by acute graft-versus-host disease and multiple organ failure. CONCLUSIONS: FG therapy is a feasible procedure and this pilot study suggests that it may be an effective treatment for refractory HC. Its application could be considered also in Grade 1 or 2 HC to prevent progression of damaged mucosa. The use of FG for HC should be prospectively investigated in terms of therapeutic efficacy, transfusion support, length of hospitalization, quality of life, and costs.


Asunto(s)
Cistitis/terapia , Adhesivo de Tejido de Fibrina/farmacología , Trasplante de Células Madre Hematopoyéticas , Hemorragia/terapia , Adolescente , Adulto , Cistitis/etiología , Cistoscopía/métodos , Femenino , Neoplasias Hematológicas/terapia , Hemorragia/etiología , Humanos , Masculino , Persona de Mediana Edad , Proyectos Piloto , Trasplante Homólogo
15.
Onkologie ; 32(3): 119-21, 2009 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-19295251

RESUMEN

BACKGROUND: Only few cases of pancreatic involvement of multiple myeloma (MM) have been reported in the medical literature. PATIENTS AND METHODS: We here report a case of devastating extramedullary relapse of IgA/lambdaMM (stage IA) treated at diagnosis with a dexamethasone, adriamycin, vincristine (DAV) regimen followed by high-dose therapy and autologous stem cell transplantation (ASCT), achieving a partial remission. After 6 years of stable disease, the patient presented symptoms of obstructive jaundice determined by a large mass of the head of the pancreas. An ultrasound-guided fine-needle aspiration cytology of the pancreatic mass revealed the presence of myeloma plasma cells. A chest X-ray demonstrated a massive right pleural effusion, and the cytomorphologic evaluation of the pleural effusion showed the presence of abnormal plasma cells. RESULTS: We observed a progression of disease despite an aggressive treatment with high-dose cyclophosphamide. CONCLUSIONS: Our case shows that extramedullary relapses of MM after ASCT are very resistant to conventional chemotherapy. The role of new drugs and the optimal treatment strategy in these cases remain to be defined.


Asunto(s)
Dolor Abdominal/prevención & control , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Cadenas lambda de Inmunoglobulina/análisis , Ictericia Obstructiva/prevención & control , Mieloma Múltiple/tratamiento farmacológico , Recurrencia Local de Neoplasia/prevención & control , Neoplasias Pancreáticas/tratamiento farmacológico , Dolor Abdominal/diagnóstico , Dolor Abdominal/etiología , Adulto , Femenino , Humanos , Ictericia Obstructiva/diagnóstico , Ictericia Obstructiva/etiología , Mieloma Múltiple/complicaciones , Mieloma Múltiple/diagnóstico , Recurrencia Local de Neoplasia/diagnóstico , Neoplasias Pancreáticas/complicaciones , Neoplasias Pancreáticas/diagnóstico , Prevención Secundaria
16.
J Endourol ; 33(2): 93-98, 2019 02.
Artículo en Inglés | MEDLINE | ID: mdl-30280911

RESUMEN

OBJECTIVE: To evaluate the clinical value of endoscopic fibrin glue (FG) application therapy in treating hemorrhagic radiation cystitis (HRC). PATIENTS AND METHODS: This is a single-cohort, prospective pilot study. We collected data from patients with HRC who were treated at our urology unit from May 2014 to December 2016. Patients with grade ≥2 HRC for whom conventional therapy and transurethral endoscopic electrocoagulation had failed were treated with endoscopic intravesical FG. The mean follow-up was 26.2 ± 9.78 months. Our analysis included data on patient demographics, pelvic malignancies, radiotherapy regimens, total dose of radiation received, time of onset and severity of hematuria, and previous intravesical management. Following FG intervention, patients' clinical status was defined as: (1) clinical response; absence of dysuria, urgency, and frequency; discontinuation of analgesic medication; and Foley catheter removal, but with ongoing hematuria grade <2; (2) complete response, clinical response, and no further hematuria; or (3) no response, no clinical response, and sustained hematuria. RESULTS: A total of 20 patients (12 women and 8 men; mean age, 69 ± 7.5 years) were treated with 12 mL FG intravesically, using endoscopic application. Of the 20 patients, 16 (80%) had a complete response and 4 (20%) had a clinical response. In the case of four patients (20%), treatment was carried out twice. Mean hospital stay was 6 ± 2.5 days. The intervention showed good tolerability in all patients. No major adverse events were reported. Bladder spasms were the only minor adverse events reported in six patients (30%). CONCLUSION: Application of FG is an effective, practical, affordable, and repeatable procedure for the treatment of grade ≥2 HRC.


Asunto(s)
Cistitis/terapia , Adhesivo de Tejido de Fibrina/administración & dosificación , Hematuria/terapia , Hemostáticos/administración & dosificación , Traumatismos por Radiación/terapia , Anciano , Estudios de Cohortes , Femenino , Humanos , Masculino , Proyectos Piloto , Estudios Prospectivos , Resultado del Tratamiento
17.
DNA Repair (Amst) ; 6(8): 1179-86, 2007 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-17500047

RESUMEN

Previous studies indicated that dacarbazine and Temozolomide could be highly effective against refractory acute leukaemia. Their activity relies mainly on the generation of methyl adducts at the O(6)-position of guanine in DNA. High levels of O(6)-methylguanine-DNA methyltransferase (MGMT) or a defective mismatch repair (MMR) system, are associated with cellular resistance to triazenes. The MGMT inhibitor, O(6)-(4-bromothenyl)guanine (Lomeguatrib), can restore in vitro sensitivity to Temozolomide in MMR-proficient blasts. In the early 1970s we discovered that, in vivo, triazene compounds induce the appearance of novel transplantation antigens in murine leukaemia ("Chemical Xenogenization", CX). Non-self peptides presented by class I MHC molecules are generated by triazene-induced somatic mutations, affecting retroviral sequences that are detectable in the mouse genome. Moreover, preliminary experiments suggested that human cancer cells can also undergo CX. Therefore, we designed a chemo-immunotherapy strategy in leukaemic patients as follows: (a) cytoreduction and a hypothetical CX phase, i.e. treatment with Lomeguatrib (to suppress MGMT activity) and Temozolomide (to kill sensitive blasts and to presumably induce CX in resistant leukaemic cells); (b) immune response recovery phase using interleukin-2 (to possibly restore an immune response and take advantage of the hypothetical, triazene-induced CX). Here we present the results of pilot study which is in progress in patients with refractory/relapsed acute leukaemia. In all tested cases, Lomeguatrib suppressed MGMT activity in vivo. Six out of eight patients showed partial or complete disappearance of blast cells in peripheral blood or in bone marrow. We observed severe and long-lasting myelosuppression, accompanied by limited non-haematological toxicity. Up to now, two patients are alive (after 9 and 10 months, respectively), four died of opportunistic infections and two of progressive disease. This investigation confirms the potential role of triazenes in leukaemia and highlights the contribution of Lomeguatrib in overcoming drug resistance. Further studies are required to establish whether Temozolomide can induce CX in human leukaemia, and thus offer a new approach to control minimal residual disease.


Asunto(s)
Dacarbazina/análogos & derivados , Interleucina-2/uso terapéutico , Leucemia/tratamiento farmacológico , Leucemia/terapia , Purinas/uso terapéutico , Animales , Antineoplásicos Alquilantes/uso terapéutico , Terapia Combinada , Metilación de ADN , Metilasas de Modificación del ADN/antagonistas & inhibidores , Reparación del ADN , Enzimas Reparadoras del ADN/antagonistas & inhibidores , Dacarbazina/uso terapéutico , Resistencia a Antineoplásicos , Inhibidores Enzimáticos/uso terapéutico , Humanos , Inmunoterapia , Ratones , O(6)-Metilguanina-ADN Metiltransferasa/antagonistas & inhibidores , Proyectos Piloto , Temozolomida , Proteínas Supresoras de Tumor/antagonistas & inhibidores
18.
PLoS One ; 13(7): e0200221, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-30036376

RESUMEN

Cytomegalovirus (CMV) infection represents one of the main cause mortality after Stem Cell Transplantation. Recently, a protective effect of the T allele of rs12979860 IL28B Single Nucleotide Polymorphisms (SNPs) against CMV infection in the allogenic stem cell transplantation was suggested. We investigate whether the rs12979860 IL28B SNP and the relative rs368234815 (IFNλ4) genotype may affect the incidence of active CMV infection in Autologous stem cell transplantation (Auto-SCT) setting. The study included 99 patients who underwent to Auto-SCT. IL28 and IFNΔ4 SNPs were correlated with CMV reactivation along with other clinical and treatment parameters. CMV reactivation by CMV DNAemia was evaluated once a week until day 100 from Auto-SCT. CMV reactivation was documented in 50% (TT-ΔG/ΔG), 35% (CC-TT/TT) and 29.2% (CT-TT/ΔG) of the patients respectively. No differences in CMV copies number were recorded at reactivation between different IL28/IFNλ4 genotypes. The analysis of patients older than 60 years showed a significantly higher incidence of active CMV infection in the TT-ΔG/ΔG (83%) population with respect to CC-TT/TT (21%) and CT-TT/ΔG (40%) patients. Our data suggest a negative role of TT-ΔG/ΔG genotype in the CMV reactivation in Auto-SCT. The exposure to rituximab and the pre-infusion presence of anti CMV IgG also significantly influenced CMV reactivation.


Asunto(s)
Infecciones por Citomegalovirus/prevención & control , Citomegalovirus/fisiología , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Interleucinas/genética , Polimorfismo de Nucleótido Simple , Trasplante Autólogo/efectos adversos , Activación Viral/genética , Adolescente , Adulto , Anciano , Alelos , Infecciones por Citomegalovirus/etiología , Infecciones por Citomegalovirus/virología , Femenino , Genotipo , Humanos , Interferones , Linfoma no Hodgkin/terapia , Masculino , Persona de Mediana Edad , Mieloma Múltiple/terapia , Adulto Joven
19.
Sci Rep ; 8(1): 5823, 2018 04 11.
Artículo en Inglés | MEDLINE | ID: mdl-29643468

RESUMEN

Circulating endothelial cells (CEC) represent a restricted peripheral blood (PB) cell subpopulation with high potential diagnostic value in many endothelium-involving diseases. However, whereas the interest in CEC studies has grown, the standardization level of their detection has not. Here, we undertook the task to align CEC phenotypes and counts, by standardizing a novel flow cytometry approach, within a network of six laboratories. CEC were identified as alive/nucleated/CD45negative/CD34bright/CD146positive events and enumerated in 269 healthy PB samples. Standardization was demonstrated by the achievement of low inter-laboratory Coefficients of Variation (CVL), calculated on the basis of Median Fluorescence Intensity values of the most stable antigens that allowed CEC identification and count (CVL of CD34bright on CEC ~ 30%; CVL of CD45 on Lymphocytes ~ 20%). By aggregating data acquired from all sites, CEC numbers in the healthy population were captured (medianfemale = 9.31 CEC/mL; medianmale = 11.55 CEC/mL). CEC count biological variability and method specificity were finally assessed. Results, obtained on a large population of donors, demonstrate that the established procedure might be adopted as standardized method for CEC analysis in clinical and in research settings, providing a CEC physiological baseline range, useful as starting point for their clinical monitoring in endothelial dysfunctions.


Asunto(s)
Recuento de Células Sanguíneas/métodos , Separación Celular/normas , Células Endoteliales , Endotelio Vascular/citología , Citometría de Flujo/normas , Adulto , Variación Biológica Poblacional , Recuento de Células Sanguíneas/normas , Separación Celular/métodos , Estudios de Factibilidad , Femenino , Citometría de Flujo/métodos , Voluntarios Sanos , Hematología/métodos , Hematología/normas , Humanos , Laboratorios/normas , Masculino , Persona de Mediana Edad , Valores de Referencia , Sensibilidad y Especificidad , Adulto Joven
20.
J Orthop Res ; 35(10): 2109-2116, 2017 10.
Artículo en Inglés | MEDLINE | ID: mdl-28019703

RESUMEN

Intervertebral disc regeneration is quickly moving towards clinical applications. However, it is still missing an ideal injectable hydrogel to support mesenchymal stem cells (MSC) delivery. Herein, a new injectable hydrogel composed of platelet rich plasma (PRP) and hyaluronic acid (HA) blended with batroxobin (BTX) as gelling agent, was designed to generate a clinically relevant cell carrier for disc regeneration. PRP/HA/BTX blend was tested for rheological properties. Amplitude sweep, frequency sweep, and rotational measurements were performed and viscoelastic properties were evaluated. Human MSC encapsulated in PRP/HA/BTX hydrogel were cultured in both growing medium and medium with or without TGF-ß1 up to day 21. The amount of glycosaminoglycan was evaluated. Quantitative gene expression evaluation for collagen type II, aggrecan, and Sox 9 was also performed. Rheological tests showed that the hydrogel jellifies in 15 min 20°C and in 3 min at 37°C. Biological test showed that MSCs cultured in the hydrogel maintain high cell viability and proliferation. Human MSC within the hydrogel cultured with or without TGF-ß1 showed significantly higher GAG production compared to control medium. Moreover, MSCs in the hydrogel underwent differentiation to chondrocyte-like cells with TGF-ß1, as shown by histology and gene expression analysis. This novel hydrogel improves viability and proliferation of MSCs supporting the differentiation process toward chondrocyte-like cells. Rheology tests showed optimal gelation kinetics at room temperature for manipulation and faster gelation after transplantation (37°C). The clinical availability of all components of the hydrogel will allow a rapid translation of this regenerative approach into the clinical scenario. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:2109-2116, 2017.


Asunto(s)
Batroxobina , Ácido Hialurónico , Hidrogeles/síntesis química , Trasplante de Células Madre Mesenquimatosas , Plasma Rico en Plaquetas , Voluntarios Sanos , Humanos , Reología
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