RESUMO
Patients with paroxysmal nocturnal hemoglobinuria (PNH) are susceptible to complement-mediated intravascular hemolysis and thrombosis. Factor H (FH) is the main regulator of the complement alternative pathway, which protects cells from unwanted complement-mediated damage. Although FH is not a glycosylphosphatidylinositol-linked molecule, it may play a role in PNH. We sought to determine if rare germline variants in complement factor H (CFH) affect the PNH course, screening 84 patients with PNH treated with eculizumab for rare variants in CFH, CFI, and C3 genes. We compared the allelic frequencies with populational data and a geographically-matched control group, looking for an association between presence of the variants and treatment response (transfusion independence by 6 months). Sixteen patients presented rare variants, 9 in CFH (10.7%). Germline CFH variants were more frequent among patients with PNH than among controls (P = .02) or public data (P < .001) and were more likely to be transfusion-dependent at 6 months after eculizumab initiation (P = .015). With a median follow-up of 5.8 years, 8 of 9 patients with the CFH variant received transfusions, and 2 developed thromboses. None of the patients with the CFH variant had severe aplastic anemia from eculizumab initiation until 6 months. We demonstrated for the first time that rare CFH variants are over-represented among patients with PNH and that germline genetic background may affect the response to eculizumab.
Assuntos
Fator H do Complemento , Hemoglobinúria Paroxística , Trombose , Humanos , Anemia Aplástica , Fator H do Complemento/genética , Hemoglobinúria Paroxística/tratamento farmacológico , Hemoglobinúria Paroxística/genética , HemóliseRESUMO
Significant morbidity and mortality have been associated with liver complications after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Causes and consequences of these hepato-biliary complications are various and might be life-threatening. A high misdiagnosis rate has been reported because of a weak correlation between clinical, laboratory and imaging data. Liver elastography, a liver stiffness measure, is able to assess liver fibrosis and portal hypertension in most liver diseases, but data after allo-HSCT are scarce. Our aim was to determine the interest of sequential liver stiffness measurements for the diagnosis of early hepatic complications after allo-HSCT. Over a two years period of time, 161 consecutive adult patients were included and 146 were analyzed. Ultrasonography and elastography measurements were performed before transplantation, at day+7 and day+14 by three different experienced radiologists unaware of patients'clinical status. Eighty-one (55%) patients had liver involvements within the first 100 days after allo-HSCT. Baseline elastography was not predictive for the occurrence of overall liver abnormalities. A significant increase in 2D real-time shearwave elastography (2D-SWE) was found in patients with sinusoidal obstruction syndrome (SOS). Fifteen patients (10%) fulfilled EBMT score criteria and twelve (8%) reached Baltimore criteria for SOS diagnosis, but only six (4%) had a confirmed SOS. 2D-SWE at day+14 allowed early detection of SOS (AUROC=0.84, p=0.004) and improved sensibility (75%), specificity (99%) and positive predictive value (60%) over the Seattle, Baltimore or EBMT scores. A 2D-SWE measurement above 8.1kPa at day+14 after allo-HSCT seems a promising, non-invasive, and reproducible tool for early and accurate diagnosis of SOS.
Assuntos
Técnicas de Imagem por Elasticidade , Transplante de Células-Tronco Hematopoéticas , Hepatopatia Veno-Oclusiva , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Hepatopatia Veno-Oclusiva/diagnóstico por imagem , Hepatopatia Veno-Oclusiva/etiologia , Humanos , Fígado/diagnóstico por imagem , Fígado/patologia , Cirrose Hepática/patologiaRESUMO
Post-transplantation lymphoproliferative disease (PTLD) is a serious complication associated with Epstein-Barr virus (EBV) infection after hematopoietic stem cell transplantation (HSCT). Although anti-CD-20 therapy is now used as a preemptive strategy for EBV reactivation, PTLD still occurs in some patients. Here we analyzed outcomes and risk factors associated with PTLD transformation in 208 HSCT recipients who were diagnosed with EBV-DNAemia and received at least 1 course of rituximab. The median patient age was 42.52 years (range, 8.35 to 74.77 years), and the median duration of follow-up was 47.33 months (range, 3.18 to 126.20 months). The 2-year overall survival of the entire cohort was 62.8 (95% confidence interval [CI], 56.4 to 69.9), and the 2-year cumulative incidence function of PTLD was 6.3% (95% CI, 3.5% to 10.1%), for a median follow-up of patients diagnosed with PTLD of 37.85 months. Multivariable analysis identified 4 risk factors associated with PTLD: HSCT from an unrelated donor, recipient HLA-DRB1*11:01, fever at diagnosis of EBV infection, and donor-recipient sex-mismatched HSCT. The presence of more than 2 of these risk factors was associated with an increased risk of developing PTLD. This retrospective study identifies risk factors associated with PTLD in EBV-infected patients after HSCT and defines patient subgroups that may benefit from intensified preemptive strategies.
Assuntos
Infecções por Vírus Epstein-Barr , Transplante de Células-Tronco Hematopoéticas , Herpesvirus Humano 4/metabolismo , Rituximab/efeitos adversos , Adulto , Idoso , Criança , Infecções por Vírus Epstein-Barr/induzido quimicamente , Infecções por Vírus Epstein-Barr/diagnóstico , Infecções por Vírus Epstein-Barr/metabolismo , Feminino , Seguimentos , Cadeias HLA-DRB1/metabolismo , Humanos , Transtornos Linfoproliferativos/induzido quimicamente , Transtornos Linfoproliferativos/diagnóstico , Transtornos Linfoproliferativos/metabolismo , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Rituximab/administração & dosagemRESUMO
In the case of donor/recipient rhesus (Rh)-incompatibility after allogeneic hematopoietic stem cell transplantation (alloHSCT), the transfusion policy in France is to transfuse red blood cells (RBC) in the donor's Rh phenotype from the day of transplantation, leading to a risk of allo-immunization, either of donor or recipient origin. In this single-center retrospective study, the incidence of donor/recipient Rh incompatibility was 7.1% over an 8-year period including 1012 alloHSCT. Six of 58 evaluable patients (10.3%) developed alloantibodies to RBC antigens within one year of alloHSCT. None of these allo-immunizations were directed against the donor-mismatched Rh antigens and none could have been prevented by the transfusion of recipient and donor Rh-compatible RBC units. None of these allo-immunizations led to immune-mediated hemolytic anemia. We observed a statistically significant higher incidence of chronic GVHD among patients with anti-RBC allo-immunization. In the context of donor/recipient Rh incompatibility, the transfusion of packed RBC units in the donor's Rh phenotype from the day of alloHSCT is feasible and not associated with a high risk of allo-immunization. The generalization of this strategy could be discussed even when donor and recipient Rh phenotypes could be respected, to allow the preservation of units of infrequent phenotypes for other indications.
RESUMO
Systemic sclerosis (SSc) is a rare autoimmune disease (AD), characterised by early diffuse vasculopathy, activation of the immune response and progressive skin and internal organ fibrosis. In severe progressive diffuse SSc (dSSc), autologous hematopoietic stem cell transplantation (aHSCT) improves survival, despite its own risk of complications and transplant related mortality (TRM). We present herein the case of a dSSc patient undergoing aHSCT with low dose cyclophosphamide conditioning and sudden acute myopericarditis and cardiogenic shock, four weeks after a second mRNA SARS-CoV-2 vaccine (Pfizer) injection. Four days of extracorporeal membrane oxygenation (ECMO) support during the aplasia period, allowed to observe full cardiac function recovery and progressive SSc rehabilitation with sustained disease response at 30 months follow-up. This report illustrates, for the first time to our knowledge, that ECMO can be indicated despite aplasia during aHSCT and successfully used as a bridge towards heart function recovery in highly selected and fragile AD patients. We review the factors that may contribute to endothelial and myocardial stunning and acute reversible cardiac failure in SSc and aggravate intrinsic endothelial injury during the aHSCT procedure. These classically include: cyclophosphamide drug toxicity, viral infections and autoimmune activation with disease flair per se. In the COVID-19 pandemic times, acute myocarditis due to recent viral infection or mRNA vaccine per se, must also be considered.
RESUMO
BACKGROUND: Acute schistosomiasis is a systemic hypersensitivity reaction against the migrating schistosomula and eggs. In this report, we describe an atypical outbreak of the disease with severe cases. Transmission occurred in a nonendemic area of Brazil, which became a new focus of transmission due to the in-migration of infected workers. METHODS: From December 2009 to March 2010, the 50 patients with acute schistosomiasis (group 1) bathed in a swimming pool supplied by a brook on a country estate in the outskirts of São João del Rei, Brazil. Thirty other subjects (group 2) living in the same area, who denied having contact with the swimming pool, volunteered to participate in the study. All participants were submitted to clinical, laboratory, and ultrasound examinations. RESULTS: Five of 50 (10%) patients were admitted to the hospital: 1 with myeloradiculopathy, 1 with diffuse pulmonary micronodules, and 3 with diarrhea and dehydration. All 5 had hypereosinophilia and prolonged fever. Group 1 patients more frequently had cercarial dermatitis (P = .01), blood in the stool (P = .04), and intra-abdominal lymph nodes (P = .001). All group 1 patients were treated with praziquantel; 1 patient with myeloradiculopathy also received oral prednisone (60 mg/day) for 6 months with complete recovery. CONCLUSIONS: This report describes the first time that patients from an outbreak of acute schistosomiasis have been compared to controls. Five subjects (10%) had severe manifestations of schistosomiasis. Diagnosis of the disease and its severity was delayed because physicians did not consider that an epidemic of schistosomiasis might emerge in a nonendemic area.
Assuntos
Surtos de Doenças , Schistosoma mansoni/isolamento & purificação , Esquistossomose mansoni/epidemiologia , Esquistossomose mansoni/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Anti-Helmínticos/uso terapêutico , Brasil/epidemiologia , Estudos de Casos e Controles , Criança , Pré-Escolar , Feminino , Voluntários Saudáveis , Humanos , Masculino , Pessoa de Meia-Idade , Praziquantel/uso terapêutico , Esquistossomose mansoni/transmissão , Resultado do Tratamento , Adulto JovemAssuntos
Leucemia Mieloide Aguda , Mutação , Proteínas de Neoplasias/administração & dosagem , Proteínas Nucleares/genética , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos , Intervalo Livre de Doença , Feminino , Humanos , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/mortalidade , Masculino , Pessoa de Meia-Idade , Nucleofosmina , Indução de Remissão , Estudos Retrospectivos , Taxa de SobrevidaRESUMO
PURPOSE: Secondary myeloid neoplasms (sMNs) remain the most serious long-term complications in patients with aplastic anemia (AA) and paroxysmal nocturnal hemoglobinuria (PNH). However, sMNs lack specific predictors, dedicated surveillance measures, and early therapeutic interventions. PATIENTS AND METHODS: We studied a multicenter, retrospective cohort of 1,008 patients (median follow-up 8.6 years) with AA and PNH to assess clinical and molecular determinants of clonal evolution. RESULTS: Although none of the patients transplanted upfront (n = 117) developed clonal complications (either sMN or secondary PNH), the 10-year cumulative incidence of sMN in nontransplanted cases was 11.6%. In severe AA, older age at presentation and lack of response to immunosuppressive therapy were independently associated with increased risk of sMN, whereas untreated patients had the highest risk among nonsevere cases. The elapsed time from AA to sMN was 4.5 years. sMN developed in 94 patients. The 5-year overall survival reached 40% and was independently associated with bone marrow blasts at sMN onset. Myelodysplastic syndrome with high-risk phenotypes, del7/7q, and ASXL1, SETBP1, RUNX1, and RAS pathway gene mutations were the most frequent characteristics. Cross-sectional studies of clonal dynamics from baseline to evolution revealed that PIGA/human leukocyte antigen lesions decreased over time, being replaced by clones with myeloid hits. PIGA and BCOR/L1 mutation carriers had a lower risk of sMN progression, whereas myeloid driver lesions marked the group with a higher risk. CONCLUSION: The risk of sMN in AA is associated with disease severity, lack of response to treatment, and patients' age. sMNs display high-risk morphological, karyotypic, and molecular features. The landscape of acquired somatic mutations is complex and incompletely understood and should be considered with caution in medical management.
Assuntos
Anemia Aplástica , Hemoglobinúria Paroxística , Humanos , Anemia Aplástica/genética , Anemia Aplástica/patologia , Anemia Aplástica/terapia , Hemoglobinúria Paroxística/genética , Estudos Retrospectivos , Estudos Transversais , Evolução Clonal/genéticaRESUMO
Steroid-refractory graft versus host disease (GVHD) represents a fearsome complication after allogeneic hematopoietic stem cell transplantation (HSCT). We conducted a retrospective study on outcomes and risk factors associated with acute and chronic steroid-refractory GVHD in a large cohort of 1207 patients receiving HSCT in Saint Louis Hospital between 2007 and 2017. Among patients who developed an acute and/or a chronic GVHD, the cumulative incidences of acute and chronic steroid-refractory disease were 31% and 48%, respectively, at day +100 and 1-year post-HSCT. Through a multivariable analysis we selected several risk factors associated with the development of a steroid-refractory disease. For acute GVHD steroid refractoriness, we identified (1) a very high disease risk index, (2) an unrelated donor, (3) the absence of in vivo T-depletion as GVHD prophylaxis, and (4) a reduced intensity conditioning regimen. For chronic GVHD, (1) the use of peripheral blood stem cells, (2) unrelated donors, and (3) absence of in vivo T-depletion were more likely associated with a steroid-refractory disease. After the construction of a multistate dynamic model, we found that the probability of being alive without relapse after the resolution of all GVHD episodes was about 36% in the long term.
Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Análise Fatorial , Doença Enxerto-Hospedeiro/etiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Estudos Retrospectivos , Fatores de Risco , Condicionamento Pré-Transplante/efeitos adversosRESUMO
PURPOSE: To evaluate the histopathology alterations of the intestinal mucosa of rabbits submitted to different times of mesenteric artery ischemia and reperfusion with and without celiac artery collateral circulation supply. METHODS: Two groups of eight male New Zealand white rabbits (weight 2.2-3.5 kg) were used in this study. In the Group 1 animals, the proximal mesenteric artery was occluded for 60 min with an atraumatic vascular clamp, followed by reperfusion for 60 min. In the Group 2 animals the small bowel and mesentery were cut 30cm and 60cm far from the gastroduodenal pyloric transition before the proximal mesenteric artery occlusion. Small bowel biopsies were obtained before ischemia (control), after 30 min and 60 min of mesenteric ischemia and at 30 and 60 min. of mesenteric artery reperfusion. RESULTS: In the Group I animals, the followings histopathology grade results were observed: t1, mean 0.4 + 0.29; t2, mean 1.9 +/- 0.38; t3, 1.9 +/- 0.33; t4, 1.2 +/- 0.36 and t5, 1.2 +/- 0.32. Differences between t0 and t2 and between t3 and t4 were statistically significant (p<0.05). Differences between t2 and t3 and t4 and t5 were not significant (p>0.5). In the Group II animals, it was observed: t1, mean 1.6 +/- 0.33; t2, 2.4 +/- 0.36; t3, 3.0 +/- 0.35; t4 3.4 +/- 0.31; t5, 3 +/- 031. Differences between t0 and t1, t1 and t2, and t2 and t3 were significant (p<0.05). Differences between histopathology grades results of samples t1 to t5 in Group 1 and 2 were statistically significant (p<0.5). CONCLUSION: Microscopic examination of the biopsies revealed significant evidence of worse small bowel wall ischemia-reperfusion lesions by exclusion of the celiac artery collateral circulation supply.
Assuntos
Circulação Colateral , Intestino Delgado/irrigação sanguínea , Artérias Mesentéricas/fisiologia , Oclusão Vascular Mesentérica/patologia , Traumatismo por Reperfusão/patologia , Circulação Esplâncnica/fisiologia , Animais , Mucosa Intestinal/patologia , Intestino Delgado/patologia , Masculino , CoelhosRESUMO
A queimadura é dos acidentes mais frequentes em Pediatria, com altas taxas de mortalidade.As complicações mais frequentes são o choque hipovolêmico, a desnutrição progressiva e as infecções. Este artigo faz uma revisão sobre a abordagem do choque hipovolêmico na criança queimada em relação à sua fisiopatologia e as diversas modalidades de tratamento, discutindo as suas vantagens e desvantagens.
Burns are the most frequent accidents in Pediatrics, with high mortality rates. The most frequent complications are a hypovolemic shock, progressive malnutrition, and infections.This article is a review of the hypovolemic shock approach in the burned child in relation to his pathophysiology and the various treatment modalities, discussing their advantages and disadvantages.
RESUMO
PURPOSE: To evaluate the histopathology alterations of the intestinal mucosa of rabbits submitted to different times of mesenteric artery ischemia and reperfusion with and without celiac artery collateral circulation supply. METHODS: Two groups of eight male New Zealand white rabbits (weight 2.2-3.5 kg) were used in this study. In the Group 1 animals, the proximal mesenteric artery was occluded for 60 min with an atraumatic vascular clamp, followed by reperfusion for 60 min. In the Group 2 animals the small bowel and mesentery were cut 30cm and 60cm far from the gastroduodenal pyloric transition before the proximal mesenteric artery occlusion. Small bowel biopsies were obtained before ischemia (control), after 30 min and 60 min of mesenteric ischemia and at 30 and 60 min. of mesenteric artery reperfusion. RESULTS: In the Group I animals, the followings histopathology grade results were observed: t1, mean 0.4 + 0.29; t2, mean 1.9 ± 0.38; t3, 1.9 ± 0.33; t4, 1.2 ± 0.36 and t5, 1.2 ± 0.32. Differences between t0 and t2 and between t3 and t4 were statistically significant (p<0.05). Differences between t2 and t3 and t4 and t5 were not significant (p>0.5). In the Group II animals, it was observed: t1, mean 1.6 ± 0.33; t2, 2.4 ± 0.36; t3, 3.0 ± 0.35; t4 3.4 ± 0.31; t5, 3 ± 031. Differences between t0 and t1, t1 and t2, and t2 and t3 were significant (p<0.05). Differences between histopathology grades results of samples t1 to t5 in Group 1 and 2 were statistically significant (p<0.5). CONCLUSION: Microscopic examination of the biopsies revealed significant evidence of worse small bowel wall ischemia-reperfusion lesions by exclusion of the celiac artery collateral circulation supply.
OBJETIVO: Avaliar as alterações histopatológicas da mucosa intestinal de coelhos submetidos à isquemia-reperfusão com e sem exclusão da circulação mesentérica colateral. MÉTODOS: Foram estudados dois grupos de oito coelhos Nova Zelândia machos com pesos variáveis entre 2,2 e 3,5 kg de peso corpóreo. Nos animais do Grupo 1, a artéria mesentérica proximal foi ocluida por pinçamento atraumático durante 60 min, seguido de reperfusão por 60 min. No Grupo 2 o intestino delgado e o mesentério foram seccionados 30 cm e 60 após a transição pilórica gastroduodenal antes da oclusão da artéria mesentérica cranial. Biópsias da parede intestinal foram obtidas antes da isquemia (controle), após 30 e 60 min. de isquemia. RESULTADOS: No Grupo I foram observados os seguintes graus de lesões: t1,média de 0.4 + 0.29; t2, média 1.9 ± 0.38; t3, 1.9 ± 0.33; t4, 1.2 ± 0.36 e t5, 1.2 ± 0.32. As diferenças entre t0 e t2 e entre t3 e t4 foram significantes (p<0.05). As diferenças entre t2 e t3 e t4 e t5 não foram significantes (p>0.5). No Group II observou-se: t1, média de 1.6 ± 0.33; t2, 2.4 ± 0.36; t3, 3.0 ± 0.35; t4 3.4 ± 0.31; t5, 3 ± 031. As diferenças entre t0 e t1, t1 e t2, e t2 e t3 foram significantes (p<0.05). As diferenças entre os resultados histopatológicos das biopsies de t1 a t5 dos Grupos 1 e 2 foram significantes (p<0.5). CONCLUSÃO: A exclusão da circulação mesentérica colateral agravou significantemente a degeneração histopatológica na isquemia-reperfusão da parede intestinal.
Assuntos
Animais , Masculino , Coelhos , Circulação Colateral , Intestino Delgado/irrigação sanguínea , Artérias Mesentéricas/fisiologia , Oclusão Vascular Mesentérica/patologia , Traumatismo por Reperfusão/patologia , Circulação Esplâncnica/fisiologia , Mucosa Intestinal/patologia , Intestino Delgado/patologiaRESUMO
A parada cardíaca durante a gravidez apresenta altos índices de mortalidade maternae fetal que variam conforme a etiologia. Felizmente, sua ocorrência é pouco comum,sendo o número de casos estimados de um para 30.000 gestações. Segundo estudosepidemiológicos em mortalidade materna, as maiores causas de morte devido a paradacardiorrespiratória (PCR) são: tromboembolismo venoso, síndromes hipertensivasda gravidez, sepse, embolismo pelo fluido amniótico, hemorragia, trauma, causasiatrogênicas e doenças cardíacas congênitas ou adquiridas. Independentemente dacausa, uma intervenção deve ser adotada precocemente para otimizar as chances desobrevivência da mãe e/ou do feto. Dentre essas intervenções, destacam-se o suportebásico e avançado de vida, a cesariana perimortem e a cesariana postmortem, queserão abordadas neste artigo.
Cardiac arrest during pregnancy has high rates of maternal and fetal mortality, whichvary according to the etiology. Fortunately, its occurrence is uncommon, and the estimatednumber of cases is 1 for each 30,000 pregnancies5. According to epidemiologicalstudies on maternal mortality, the major causes of death due to cardiopulmonary arrestare: venous thromboembolism, hypertensive disorders of pregnancy, sepsis, pulmonaryembolism by amniotic fluid, hemorrhage, trauma, iatrogenic causes and congenital or acquiredheart conditions. Whatever the cause is, intervention must be done early, in orderto maximize the chances of survival of the mother and/or fetus. Among these interventions,the basic and advanced life support, and the perimortem and postmortem cesareansection modalities will be discussed in this review.
Assuntos
Humanos , Feminino , Gravidez , Complicações Cardiovasculares na Gravidez , Reanimação Cardiopulmonar , Cesárea , Suporte Vital Cardíaco AvançadoRESUMO
O hímen imperfurado (HI) é a causa congênita mais comum de obstrução do fluxo genital no sexo feminino. Embora seja detectável em todas as faixas etárias pela inspeção da genitália externa, o HI é um diagnóstico que muitas vezes passa despercebido. Relatamos o caso de uma adolescente virgem, com desenvolvimento normal de caracteres sexuais secundários, ausência de menarca, que apresentou um quadro clínico de abdome agudo secundário à hematocolpo por hímen imperfurado.
Imperforate hymen is the most common congenital cause of genital flow obstruction in females. Although it is noticeable in all ages by the inspection of external genitalia, imperforate hymen is commonly misdiagnosed. We present a case in which a virgo intacta adolescent, with normal secondary sexual characters, without menarche, that evolved to acute abdomen and hematocolpus due to imperforate hymen.