Sibling cord blood donor program for hematopoietic cell transplantation: the 20-year experience in the Rome Cord Blood Bank.

Umbilical cord blood (UCB) represents a source of hematopoietic stem cells for patients lacking a suitably matched and readily available related or unrelated stem cell donor. As UCB transplantation from compatible sibling provides good results in children therefore directed sibling UCB collection and banking is indicated in family who already have a child with a disease potentially treatable with an allogeneic hematopoietic stem cell transplantation. Particularly, related UCB collection is recommended when the patients urgently need a transplantation. To provide access to all patients in need, we developed a "Sibling cord blood donor program for hematopoietic cell transplantation". Here we report results of this project started 20years ago. To date, in this study a total of 194 families were enrolled, a total of 204 UCB samples were successfully collected and 15 pediatric patients have been transplanted. Recently, some authors have suggested novel role for UCB other than in the transplantation setting. Therefore, future studies in the immunotherapy and regenerative medicine areas could expand indication for sibling directed UCB collection.

Polymorphism of the complement receptor 1 gene correlates with the hematologic response to eculizumab in patients with paroxysmal nocturnal hemoglobinuria.

Complement blockade by eculizumab is clinically effective in hemolytic paroxysmal nocturnal hemoglobinuria. However, the response is variable and some patients remain dependent on red blood cell transfusions. In 72 patients with hemolytic paroxysmal nocturnal hemoglobinuria on eculizumab we tested the hypothesis that response may depend on genetic polymorphisms of complement-related genes. We found no correlation between the complement component C3 genotypes and the need for blood transfusions. On the other hand, we found a significant correlation with the HindIII polymorphism of a complement regulatory gene, the complement receptor 1 (CR1) gene. At this locus two co-dominant alleles are known, of which H (common) is associated with high expression, whereas L (rare) is associated with low expression of CR1 on red blood cells. Patients who still needed blood transfusion on eculizumab accounted for 18% of the H/H homozygotes, 33% of the H/L heterozygotes and 68% of the L/L homozygotes (P=0.016). Thus, patients with paroxysmal nocturnal hemoglobinuria who have the L/L genotype are seven times more likely to be sub-optimal responders to eculizumab. Both in vitro and in vivo we found that the CR1 HindIII genotype correlates with the abundance of paroxysmal nocturnal hemoglobinuria red cells that have bound C3, and with the kinetics of C3 binding. These results are consistent with the notion that by affecting C3 binding the CR1 genotype influences the response to eculizumab treatment, and this emerges as a novel example of pharmacogenetics.

Concurrent search for unrelated cord and volunteer donor in high-risk acute lymphoblastic leukemia.

To assess the effectiveness of the search for an unrelated donor on the outcome of patients with high-risk acute lymphoblastic leukemia, we analyzed prospectively 136 patients who underwent a search for cord blood (CB) and an unrelated volunteer donor (UD) at the same time. The probability of finding a donor was 58.2%, 70.3%, and 75.7% at 3, 6, and 12 months, respectively. The median time to find a donor was 1.8 months for CB and 3.5 months for UD. Of the 99 patients with a donor, 38.4% failed to undergo the transplant because of a relapse observed at a median of 4 months from the start of the search. In univariate analysis, absence of relapse during the search (p < 0.0001) and transplant (p = 0.004) showed a positive impact on long-term survival. In multivariate analysis, relapse during the search remained the key factor affecting survival (p < 0.0001). Since an extension of the search beyond 3 months enables only a slight increase in the probability of finding a donor compared to the increased risk of relapse, the time of the search should not exceed the 3-month time point. The simultaneous search for CB and UD increases the likelihood of performing a timely transplant.

Management of the 2009 A/H1N1 influenza pandemic in patients with hematologic diseases: a prospective experience at an Italian center.

Data derived from epidemiologic surveillance adopted at our center in hematologic and stem cell transplant patients during the 2009 influenza A (H1N1)v pandemic are reported. Of the 52 patients with influenza-like disease we observed, 37 underwent a real-time PCR evaluation and 21 had a confirmed diagnosis. Of the RT-PCR-confirmed cases, 23.8% were children (age <18 years) and 9.5% were >65 years; 47.6% presented with a pulmonary infiltrate and 33.3% with respiratory failure. Pulmonary involvement was observed more frequently in patients with comorbidities. All patients received a course of oseltamivir therapy starting an average of 1 day (range <1-2) after the onset of symptoms. No patient was transferred to the intensive care unit. The viral disease had a generally favorable outcome despite the high frequency of pulmonary involvement. A prompt clinical evaluation with an early antiviral and supportive therapy may have played a beneficial role in the outcome.

Sonication induced redox reactions of the Ojén (Andalucía, Spain) vermiculite.

Sonication in a 1:1 mixture (volume ratio) of water and concentrated H(2)O(2) (30%) is a soft method for particle size reduction of phyllosilicate minerals like vermiculites. Repeated sonication causes a particle size reduction to about 70 nm for the Santa Olalla and to 45 nm for the Ojén-vermiculite. In this context the question arises whether the strong oxidising effect of the hydrogen peroxide affects the oxidation state of the iron in the vermiculites. Therefore, the Fe(3+)/Fe(total) ratio before and after sonication was determined by means of Mössbauer spectroscopy. Whereas this ratio was found to remain almost constant in the Santa Olalla vermiculite, it increased from 0.79 to 0.85 in case of the Ojén sample. In the latter case, the oxidation is accompanied by a decrease of the layer charge. Surprisingly, sonication in pure water leads to a decrease of the Fe(3+)/Fe(total) ratio in the case of the Ojén-vermiculite, i.e., to an increase of the Fe(2+) fraction to roughly twice the value before sonication. Again the Fe(3+)/Fe(total) ratio of the Santa Olalla vermiculite remains unchanged. The surface area S(BET) of the reduced Ojén-vermiculite amounts to 50 m(2)/g, which is close to the value obtained in the presence of hydrogen peroxide. The results presented should be taken as a warning that particle size reduction by sonication may be accompanied by a change of the redox state and the layer charge of the material.

B-cell concentration in the apheretic product predicts acute graft-versus-host disease and treatment-related mortality of allogeneic peripheral blood stem cell transplantation.

BACKGROUND: The influence of the graft composition on the clinical outcome after allogeneic peripheral blood stem cell (PBSC) transplantation is not well established. METHODS: The cellular composition of the apheretic products obtained from 63 human leukocyte antigen-identical siblings was prospectively correlated with the outcome of patients with hematological malignancies undergoing an allogeneic PBSC transplant after myeloablative conditioning. The concentration of nuclear, mononuclear, CD34+, T-cell subsets, B cells, and natural killer cells in the graft has been analyzed. RESULTS: In univariate analysis, acute graft-versus-host disease (GVHD) correlated with the disease (P=0.002), with the phase of disease at transplant (P=0.01), and with the number of CD20+ cells infused (P=0.05). In multivariate analysis, a dose of CD20+ cells in the graft higher than the median dose remained the only factor negatively affecting the incidence of acute GVHD (P=0.01; 95% confidence interval [CI]: 0.12-0.78). In univariate analysis, treatment-related mortality (TRM) correlated with the disease (P=0.04) and was negatively affected by a dose of infused B cells greater than the median value (28% versus 50%; P=0.02). In multivariate analysis, TRM was close to statistical correlation with the dose of CD20+ cells (P=0.06; 95% CI: 0.02-1.05). No other clinical parameter was influenced by the composition of the graft. CONCLUSIONS: Our results suggest that the concentration of B cells in the apheretic product may predict the incidence of acute GVHD and TRM in patients undergoing an allogeneic PBSC transplantation and open the way to the new preventive and therapeutic strategies for the management of GVHD.

Clinical features and outcome of familial chronic lymphocytic leukemia.

The prognostic impact of the presence of a familial trait was analyzed in 1449 patient with chronic lymphocytic leukemia (CLL). A family history of hematologic malignancy (HM) was identified in 181 cases (12.5%) and recorded more frequently among female than male patients (HM: p < 0.05; CLL: p < 0.05). The relative was affected by CLL in 89 cases (6%). Familial and sporadic cases showed non-statistically different proportions of advanced stages (10.8 vs 7.1%) and patients requiring therapy (55 vs 60%) and a similar survival probability at 10 years (67 vs 66%). These data suggest that in CLL the presence of a familial trait does not imply an adverse prognosis.

[Indications and risk factors for emergency obstetric hysterectomy]. / Indicaciones y factores de riesgo para histerectomía obstétrica de urgencia.

Emergency obstetric hysterectomy is a procedure that potentially preserves the life and the postpartum bleeding is the direct cause of its indication, the hemorrhage postpartum happens in 1% of obstetric patients. This study was carried out to identify women with potential risk for this event and to prevent this obstetric problem. The most frequent indications for hysterectomy were identified, as well as the sociodemographic characteristic of the patients. The surgical procedure carried out was extra-fascial technique with type Richardson hysterectomy modified; the surgical pieces went to the pathology service, to obtain the histopathological diagnosis. 43 cases of obstetric hysterectomy, were analyzed; the characteristics of this group showed that bigger percentage of this event was more frequent in 31 to 35 years (39.5%), with pregnancies at term (51.1%) in third pregnancies(27.9%), nulliparas (60.4%), with first cesarean section (39.5%), without previous abortions (79.0%). The most frequent obstetric complications were uterine atony and placenta accreta. The cause for uterine atony could be interstitial edema, as well as myometrial hypertrophy, because such histopathological diagnoses were the most common. Odds ratio showed that a patient with cesarean section has 1.16 more probabilities of suffering hysterectomy than a woman with childbirth. This study describes the histological presence of interstitial edema and myometrial hypertrophy as possible causes of uterine atony in the histological study of surgical specimen. This could be related to no response of myometrial to the uterus-tonic effect of oxytocin. Obstetric uterine dysfunction has multifactorial cause. Patients with the characteristics described in this study should be considered as high risk.

A systematic analysis of bone marrow cells by flow cytometry defines a specific phenotypic profile beyond GPI deficiency in paroxysmal nocturnal hemoglobinuria.

BACKGROUND: Paroxysmal nocturnal hemoglobinuria (PNH) is a unique disorder caused by a PIG-A gene mutation in a stem cell clone. Its clinical picture can sometimes make challenging the distinction from other disorders, and especially from myelodysplastic syndromes (MDS), since both diseases correlate with cytopenias and morphological abnormalities of bone marrow (BM) cells. Recently, flow cytometry (FC) has been proposed to integrate the morphologic assessment of BM dysplasia, and thus to improve the diagnostics of MDS. METHODS: In the present study, we have analyzed systematically FC data resulting from the study of BM cells from patients with PNH and MDS. RESULTS: Our data demonstrated abnormalities in PNH beyond the deficiency of glycosylphosphatidylinositol-linked proteins and the application of a systematic approach allowed us to separate effectively MDS and PNH in a cluster analysis and to highlight disease-specific abnormalities. Indeed, the parallel evaluation of some key parameters, i.e. patterns of expression of CD45 and CD10, provided information with practical diagnostic usefulness in the distinction between PNH and MDS. Moreover, the hypo-expression of CD36 that we observed on monocytes might be related to the thrombotic tendency in PNH. CONCLUSIONS: We investigated systematically the phenotypic profile of BM cells from patients with PNH; our data provide useful antigenic patterns to solve between PNH and MDS, sometimes morphologically overlapping. Moreover, some PNH-related phenotypic changes might be involved in the physiopathology of the disease and further studies addressing this issue are warranted.

The immune reconstitution after an allogeneic stem cell transplant correlates with the risk of graft-versus-host disease and cytomegalovirus infection.

Aim of the study was to correlate the clinical outcome of eighteen patients who have undergone an allogeneic stem cell transplant (SCT) with the concentration in the peripheral blood (PB) of lymphocyte subpopulations evaluated at 1 year from transplant. The occurrence of acute GVHD and CMV infection correlated with the concentration of Tregs in the PB; CMV infection also correlated with the content of NK cells. The obtained results document that the concentration of Tregs in the PB after an allogeneic SCT may protect from GVHD and from CMV infection; the potential anti-viral role of NK cells is confirmed.

Second-generation tyrosine kinase inhibitors before allogeneic stem cell transplantation in patients with chronic myeloid leukemia resistant to imatinib.

Philadelphia-positive chronic myeloid leukemia (Ph+ CML) patients who are resistant to imatinib are commonly treated with second-generation tyrosine kinase inhibitors (TKIs). Limited data exist on the possible effects of these drugs on subsequent allogeneic hematopoietic stem cell transplantation (allo-HSCT).The outcome of 12 imatinib-resistant CML patients treated with dasatinib or nilotinib or both before allo-HSCT, was retrospectively analyzed. Patients were treated with second-generation TKIs for 1-17 months (median, 8). At the time of transplant, 3 patients were in complete cytogenetic response (CCgR), 3 patients in partial cytogenetic response (PCgR) and 6 patients were in less than PCgR. Donors were HLA-matched related in 4 cases and unrelated in 8 cases. Stem cell source was peripheral blood, bone marrow or cord blood in 6, 5 and 1 cases, respectively. All patients engrafted successfully and all but one achieved a full donor chimerism. Three patients experienced acute and chronic graft-versus-host disease. No cases of transplant-related mortality were recorded. Best response to allo-HSCT was complete molecular response (CMR) in 9 patients, major molecular response (MMR) in 1 patient and CCgR in 2 patients. Median follow-up was 16.5 months. At the last evaluation, 9 patients were in continuous CMR and 1 patient was in MMR; 2 patients had died of disease progression. Second-generation TKIs given before allo-HSCT do not negatively affect transplant engraftment and response rate, nor increases transplant-related toxicity.

Inimputabilidade: estudo dos internos do Instituto Psiquiátrico Forense Maurício Cardoso / Nonimputability: a study on inmates at Instituto Psiquiátrico Forense Maurício Cardoso

INTRODUÇÃO: A pesquisa traçou um perfil dos internos inimputáveis do Instituto Psiquiátrico Forense Maurício Cardoso. MÉTODOS: Durante o período de abril a agosto de 2005, foram selecionados 617 sujeitos para inclusão no estudo. RESULTADOS: A análise dos dados revelou que os internos apresentam as seguintes características: idade média de 43,22 anos, sexo masculino (91,3 por cento), profissão definida (73,2 por cento), primeiro grau completo (74,6 por cento), sem companheiro(a) (83,2 por cento), crime contra a pessoa como delito gerador da inimputabilidade (62,1 por cento), com antecedentes criminais (58,3 por cento), prazo mínimo fixado na sentença de 1,76 anos, cumprindo medida de segurança detentiva (91,4 por cento), média do tempo de internação de 9,33 anos, sob o regime de alta progressiva (81,5 por cento), com internação prévia em outras instituições psiquiátricas (55,2 por cento), sem cumprimento anterior de medida de segurança (83,3 por cento), com o diagnóstico de esquizofrenia e outros transtornos psicóticos (61,4 por cento). Os cruzamentos de variáveis que tiveram relevância estatística foram: dos internos com internação prévia, 61,9 por cento possuíam antecedentes criminais, e quanto maior o nível de escolaridade do interno, menor o índice de reincidência. Evidenciou-se uma preponderância de internos com antecedentes criminais em pacientes com transtornos relacionados a substâncias (56,5 por cento) e transtorno de personalidade (59,7 por cento). Verificou-se que 60,8 por cento daqueles que cometeram crimes contra a pessoa possuíam diagnóstico de transtornos relacionados ao álcool, estabelecendo uma relação entre criminalidade violenta e os transtornos de uso de substâncias. CONCLUSÕES: A partir da análise dos prontuários dos 617 internos do Instituto Psiquiátrico Forense Maurício Cardoso, o presente estudo procurou apresentar um mapa dos indivíduos considerados inimputáveis no Rio Grande do Sul.

INTRODUCTION: This study analyzed the profile of nonimputable inmates at Instituto Psiquiátrico Forense Maurício Cardoso. METHODS: Between April and August 2005, a total of 617 patients were selected for inclusion in the study. RESULTS: Data analysis revealed that the inmates presented the following characteristics: mean age of 43.22 years, male (91.3 percent), defined profession (73.2 percent), completed elementary school (74.6 percent); without a partner (83.2 percent), crime against a person was the felony that generated nonimputability (62.1 percent), criminal records (58.3 percent), minimal sentence time was 1.76 years, serving it in criminal commitment (91.4 percent), mean time in prison of 9.33 years, under regime of progressive release (81.5 percent), previous hospitalization in other psychiatric institutions (55.2 percent), no previous probation measure (83.3 percent), diagnosis of schizophrenia and other psychotic disorders (61.4 percent). The following variables were statistically significant: among inmates with previous hospitalization, 61.9 percent had criminal history; and the higher the inmates' schooling level, the lower the level of criminal relapse. Results showed a predominance of inmates with criminal records in patients with disorders related to substances (56.5 percent) and personality disorder (59.7 percent). It was also verified that 60.8 percent of those who committed crimes against a person were alcohol addicts, establishing a relation between violent criminality and disorders caused by substance misuse. CONCLUSIONS: Based on the analysis of the medical records of 617 inmates at Instituto Psiquiátrico Forense Maurício Cardoso, this study aimed at presenting a map of individuals considered nonimputable in Rio Grande do Sul.

Depressão pós-parto e suas repercussões na interação precoce mãe-bebê / Depression postpartum and its repercussions in the precocious interaction mother-baby

A gestação e o puerpério são períodos da vida da mulher que necessitam ser avaliados com atenção especial, pois envolvem inúmeras alterações físicas, hormonais, e, sobretudo psíquicas e de inserção social. Essas refletem diretamente na saúde mental das pacientes e em suas funções e cuidados maternos necessários ao bebê, podendo repercutir de maneira negativa no desenvolvimento físico e emocional de seus filhos.

Violência contra o médico / Violence against the doctor

Os autores relatam e analisam a relação médico-paciente abalada por situações que colocam o médico como sujeito vulnerável quando vítima de agressões, sejam elas físicas ou morais, exercidas por seus pacientes. Questionam a capacidade deste profissional de oferecer condições de saúde, quando lhe falta à própria segurança por se encontrar em condições de violência emocional.

Doutor, o senhor pode me dar um atestado? / Doctor, you can give me a health certificate?

Este estudo faz uma revisão dos preceitos sobre atestado médico, segundo o Código de Ética Médica e revisão de alguns artigos científicos sobre o tema. Avaliação das diferentes condutas médicas quanto ao assunto e discussão sobre quais sentimentos e objetivos propulsionam cada conduta. Observação de impasses éticos, filosóficos, morais que ocasionam, algumas vezes, divergências entre a rotina do médico e o previsto no Código de Ética Médica sobre o fornecimento de atestados.