RESUMEN
Because immune responses simultaneously defend and injure the host, the immune system must be finely regulated to ensure the host's survival. Here, we have shown that when injected with high Toll-like receptor ligand doses or infected with lymphocytic choriomeningitis virus (LCMV) clone 13, which has a high viral turnover, inflammatory monocyte-derived dendritic cells (Mo-DCs) engulfed apoptotic erythroid cells. In this process, called hemophagocytosis, phosphatidylserine (PS) served as an "eat-me" signal. Type I interferons were necessary for both PS exposure on erythroid cells and the expression of PS receptors in the Mo-DCs. Importantly, hemophagocytosis was required for interleukin-10 (IL-10) production from Mo-DCs. Blocking hemophagocytosis or Mo-DC-derived IL-10 significantly increased cytotoxic T cell lymphocyte activity, tissue damage, and mortality in virus-infected hosts, suggesting that hemophagocytosis moderates immune responses to ensure the host's survival in vivo. This sheds light on the physiological relevance of hemophagocytosis in severe inflammatory and infectious diseases.
Asunto(s)
Apoptosis/inmunología , Células Dendríticas/inmunología , Virus de la Coriomeningitis Linfocítica/inmunología , Fagocitosis , Animales , Diferenciación Celular , Células Dendríticas/metabolismo , Células Eritroides/inmunología , Interferón Tipo I/metabolismo , Interleucina-10/biosíntesis , Activación de Linfocitos , Coriomeningitis Linfocítica/inmunología , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Monocitos/inmunología , Monocitos/metabolismo , Fosfatidilserinas/metabolismo , Receptores de Superficie Celular/metabolismo , Linfocitos T Citotóxicos/inmunologíaRESUMEN
Protein crystallization in human tissue rarely occurs. Charcot-Leyden crystals (CLCs) were described in various eosinophilic diseases >150 years ago, but our understanding of CLC formation still remains limited. In this study, we demonstrate that CLCs observed in varied inflamed human tissues are closely associated with eosinophil cell-free granules and nuclear envelope/plasma membrane disintegration with release of filamentous chromatin (extracellular traps), typical morphologies of a regulated pathway of extracellular trap cell death (ETosis). During the process of eosinophil ETosis, eccentrically localized cytoplasmic and perinuclear CLC protein (galectin-10) is homogeneously redistributed in the cytoplasm. Rapid (1-2 minutes) formation of intracytoplasmic CLCs was observed using time-lapse imaging. Plasma membrane rupture enabled the release of both intracellularly formed CLCs and soluble galectin-10 that further contributed to formation of CLCs extracellularly, in parallel with the expulsion of free intact granules and extracellular traps. CLC formation and galectin-10 release were dependent on nicotinamide adenine dinucleotide phosphate oxidase activation. To our knowledge, this is the first demonstration of natural formation of CLCs in association with an active physiological process (ie, ETosis). These results indicate that dynamic changes in intracellular localization and release of galectin-10 contribute to CLC formation in vivo and suggest that CLC/galectin-10 might serve as an indicator of ETosis.
Asunto(s)
Muerte Celular , Eosinófilos/patología , Trampas Extracelulares/inmunología , Galectinas/análisis , Inflamación/patología , Membrana Celular/inmunología , Membrana Celular/patología , Cristalización , Eosinófilos/citología , Eosinófilos/inmunología , Galectinas/inmunología , Humanos , Inflamación/inmunologíaRESUMEN
Although allogeneic hematopoietic stem cell transplantation (HSCT) has been reported to provide prolonged remission of relapsed/refractory mycosis fungoides (MF) and Sézary syndrome (SS), its role has not been fully evaluated. Here, the outcomes of allogeneic HSCT for patients with MF/SS were retrospectively evaluated by using the registry database of the Japan Society for Hematopoietic Cell Transplantation. Forty-eight patients were evaluable and enrolled in the analysis. Median age was 45.5 years. Eighteen patients (38%) received myeloablative conditioning, and 33 (69%) received HSCT from an alternative donor. Disease status was complete or partial response in 25% of the patients and relapsed or refractory in the others. At the time of analysis, 18 patients were alive, with a median follow-up of 31.0 months (range, 3.8-31.1). Three-year overall survival (OS) and progression-free survival (PFS) were 30% (95%CI, 16-45%) and 19% (95%CI, 9-31%), respectively. Disease progression was not observed later than 17 months after transplantation. Both disease status and performance status at transplant significantly affected OS and PFS. Although our findings suggest that allogeneic HSCT provides long-term PFS in patients with MF/SS, the timing of transplantation should be decided carefully based on the disease status and the patient's condition in order to improve the outcome.
Asunto(s)
Enfermedad Injerto contra Huésped/mortalidad , Trasplante de Células Madre Hematopoyéticas/mortalidad , Micosis Fungoide/mortalidad , Síndrome de Sézary/mortalidad , Adulto , Femenino , Estudios de Seguimiento , Enfermedad Injerto contra Huésped/patología , Enfermedad Injerto contra Huésped/terapia , Humanos , Masculino , Persona de Mediana Edad , Micosis Fungoide/patología , Micosis Fungoide/terapia , Pronóstico , Estudios Retrospectivos , Síndrome de Sézary/patología , Síndrome de Sézary/terapia , Tasa de Supervivencia , Acondicionamiento Pretrasplante , Trasplante Homólogo , Adulto JovenRESUMEN
The choice of alternative donor is a major issue in allogeneic hematopoietic stem cell transplantation (HSCT) for patients with primary myelofibrosis (PMF) without an HLA-matched related donor. We conducted this retrospective study using the Japanese national registry data for 224 PMF patients to compare the outcomes of first allogeneic HSCT from HLA-matched related donor bone marrow (Rtd-BM), HLA-matched related donor peripheral blood stem cells (Rtd-PB), HLA-matched unrelated donor bone marrow (UR-BM), unrelated umbilical cord blood (UR-UCB), and other hematopoietic stem cell grafts. Nonrelapse mortality (NRM) rates at 1 year after Rtd-BM, Rtd-PB, UR-BM, UR-UCB, and other transplantations were 16%, 36%, 30%, 41%, and 48%, respectively. Multivariate analysis identified UR-UCB transplantation, other transplantation, frequent RBC transfusion before transplantation, and frequent platelet (PLT) transfusion before transplantation as predictive of higher NRM. Relapse rates at 1 year after Rtd-BM, Rtd-PB, UR-BM, UR-UCB, and other transplantation were 14%, 17%, 11%, 14%, and 15%, respectively. No specific factor was associated with the incidence of relapse. Overall survival (OS) at 1 and 4 years after Rtd-BM, Rtd-PB, UR-BM, UR-UCB, and other transplantation were 81% and 71%, 58% and 52%, 61% and 46%, 48% and 27%, and 48% and 41%, respectively. Multivariate analysis identified older patient age, frequent RBC transfusion before transplantation, and frequent PLT transfusion before transplantation as predictive of lower OS. In conclusion, UR-UCB transplantation, as well as UR-BM transplantation, can be selected for PMF patients without an HLA-identical related donor. However, careful management is required for patients after UR-UCB transplantation because of the high NRM. Further studies including more patients after HLA-haploidentical related donor and HLA-mismatched unrelated donor transplantation would provide more valuable information for patients with PMF when making decisions regarding the choice of alternative donor.
Asunto(s)
Trasplante de Células Madre de Sangre del Cordón Umbilical , Células Madre Hematopoyéticas , Trasplante de Células Madre de Sangre Periférica , Mielofibrosis Primaria , Donante no Emparentado , Adulto , Anciano , Aloinjertos , Supervivencia sin Enfermedad , Transfusión de Eritrocitos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Mielofibrosis Primaria/sangre , Mielofibrosis Primaria/mortalidad , Mielofibrosis Primaria/terapia , Sistema de Registros , Estudios Retrospectivos , Tasa de SupervivenciaRESUMEN
Second allogeneic hematopoietic stem cell transplantation is a curative treatment option for patients with hematologic malignancies. However, it is unclear whether HLA discrepancy between graft and first donor has an impact on the outcome of second transplantation. We retrospectively analyzed 646 patients receiving second transplantation after an initial HLA mismatched transplantation. With regard to graft-versus-host, the one-allele mismatch (1 mismatch) group (SHR, 1.88; 95%CI: 0.79-4.45; P=0.163) and more than one-allele mismatch group (≥ 2 mismatch) (SHR, 1.84; 95%CI, 0.75-4.51; P=0.182) had higher risks of grade III-IV acute graft-versus-host disease (GvHD) compared to the HLA-matched (0 mismatch) group. In contrast, no difference in risk of acute GvHD was found among the 0, 1, and ≥ 2 mismatch group with respect to graft-versus-first donor. With regard to graft-versus-host, the ≥ 2 mismatch group showed a significantly higher risk of treatment-related mortality (SHR, 1.90; 95%CI, 1.04-3.50; P=0.038) compared to the 0 mismatch group, while the risk of relapse was slightly lower in the ≥ 2 mismatch group (SHR, 068; 95%CI, 0.44-1.06; P=0.086). In contrast, with regard to graft-versus-first donor, there were no significant differences in treatment-related mortality or relapse among the three groups. These findings suggested that HLA discrepancy between graft and host induces transplant-related immunological responses in second transplantation leading to an increase in treatment-related mortality, in contrast, the biological effects of HLA discrepancy between graft and first donor on outcome may be negligible.
Asunto(s)
Enfermedad Injerto contra Huésped/mortalidad , Antígenos HLA/inmunología , Neoplasias Hematológicas/mortalidad , Trasplante de Células Madre Hematopoyéticas/mortalidad , Recurrencia Local de Neoplasia/mortalidad , Donantes de Tejidos/provisión & distribución , Adolescente , Adulto , Anciano , Femenino , Estudios de Seguimiento , Enfermedad Injerto contra Huésped/inmunología , Neoplasias Hematológicas/inmunología , Neoplasias Hematológicas/patología , Neoplasias Hematológicas/terapia , Prueba de Histocompatibilidad , Humanos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/inmunología , Recurrencia Local de Neoplasia/patología , Recurrencia Local de Neoplasia/terapia , Pronóstico , Estudios Retrospectivos , Tasa de Supervivencia , Acondicionamiento Pretrasplante , Trasplante Homólogo , Adulto JovenRESUMEN
PURPOSE OF REVIEW: Charcot-Leyden crystals (CLCs), slender bipyramidal hexagonal crystals, were first described by Jean-Martin Charcot in 1853, predating Paul Ehrlich's "discovery" of eosinophils by 26 years. To date, CLCs are known as a classical hallmark of eosinophilic inflammation. CLC protein expresses palmitate cleaving lysophospholipase activity and is a member of the family of S-type lectins, galectin-10. We summarize current knowledge regarding the pathological observations of CLCs and their mechanism of generation focusing on eosinophil cell death. RECENT FINDINGS: The presence of CLCs in vivo has been consistently associated with lytic eosinophils. Recent evidence revealed that cytolysis represents the occurrence of extracellular trap cell death (ETosis), an active non-apoptotic cell death process releasing filamentous chromatin structure. Galectin-10 is a predominant protein present within the cytoplasm of eosinophils but not stored in secretory granules. Activated eosinophils undergo ETosis and loss of galectin-10 cytoplasmic localization results in intracellular CLC formation. Free galectin-10 released following plasma membrane disintegration forms extracellular CLCs. Of interest, galectin-10-containing extracellular vesicles are also released during ETosis. Mice models indicated that CLCs could be a novel therapeutic target for Th2-type airway inflammation. The concept of ETosis, which represents a major fate of activated eosinophils, expands our current understanding by which cytoplasmic galectin-10 is crystalized/externalized. Besides CLCs and free galectin-10, cell-free granules, extracellular chromatin traps, extracellular vesicles, and other alarmins, all released through the process of ETosis, have novel implications in various eosinophilic disorders.
Asunto(s)
Cristalización/métodos , Eosinofilia/metabolismo , Trampas Extracelulares/metabolismo , Galectinas/metabolismo , Animales , Cristalización/instrumentación , Modelos Animales de Enfermedad , Humanos , Inflamación/metabolismo , Inflamación/patología , RatonesRESUMEN
The original version of this article incorrectly listed the third author's name. It should be Yohei Yamamoto, not Yamamoto Yohei.
RESUMEN
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a curative therapeutic option for patients with chronic myelomonocytic leukemia (CMML). We retrospectively compared the post-transplantation outcomes of 159 patients with CMML who underwent allo-HSCT using 4 types of donor sources: HLA-matched related donor graft, unrelated bone marrow (U-BM), unrelated cord blood (U-CB), and HLA-mismatched related donor graft. The median patient age at allo-HSCT was 54 years (range, 16 to 75 years). In multivariate analyses, the use of HLA-matched related donor grafts correlated with better overall survival than U-BM (hazard ratio [HR], 2.05; 95% confidence interval [CI], 1.21 to 3.48; P = .008), U-CB (HR, 3.80; 95% CI, 2.07 to 6.95; P < .001), or HLA-mismatched related donor grafts (HR, 6.18; 95% CI, 2.70 to 14.15; P < .001). Mortality after the relapse or progression of CMML did not significantly differ among the 4 types of donor source. Transplantation-related mortality was highest in recipients of U-CB (HR, 3.32; 95% CI, 1.33 to 8.26; P = .010). In patients with CMML, allo-HSCT using an alternative donor may contribute to durable remission; however, further improvements in transplantation-related mortality are required for this type of transplantation.
Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Leucemia Mielógena Crónica BCR-ABL Positiva/mortalidad , Leucemia Mielógena Crónica BCR-ABL Positiva/terapia , Adolescente , Adulto , Factores de Edad , Anciano , Aloinjertos , Supervivencia sin Enfermedad , Femenino , Humanos , Japón/epidemiología , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Tasa de SupervivenciaRESUMEN
POEMS syndrome is a rare plasma cell dyscrasia presenting with polyneuropathy, λ-type M protein, vascular endothelial growth factor elevation, and systemic manifestations. The standard treatment has not been established, but autologous stem cell transplantation (ASCT) has exhibited effectiveness in this syndrome. However, the efficacy and long-term outcomes of ASCT have not been systematically studied. To clarify the efficacy and long-term outcomes of ASCT-treated patients in Japan, we performed a multicenter retrospective study assessing the clinical course of patients registered to the Japan Society for Hematopoietic Cell Transplantation Transplant Registry Unified Management Program (TRUMP) database. Between January 2000 and December 2011, 95 patients (58 men) were registered to the TRUMP database with a median age of 53 years (range, 28 to 72). The conditioning regimen was melphalan in 93 of 94 patients (99%), and 69 patients (74.2%) received a melphalan dose ≥ 200 mg/m2. The median CD34 cell dose was 2.47 × 106/kg (range, .31 to 20). After ASCT, patient performance status was dramatically improved (Eastern Cooperative Oncology Group performance status 0 to 1: 20.0% versus 71.6%, P < .0001). Over a median follow-up of 46.6 months 10 patients died, and 5-year overall survival was 88.8% (n = 95). Progression-free survival at 3 years was 78.3% (n = 70; median follow-up, 54.4 months). These data support the promising role of ASCT in patients with POEMS syndrome for both prolonging survival and improving quality of life. However, disease recurrence remains a major issue for long-term survivors.
Asunto(s)
Trasplante de Células Madre Hematopoyéticas/métodos , Síndrome POEMS/terapia , Sobrevivientes , Trasplante Autólogo/métodos , Adulto , Anciano , Bases de Datos Factuales , Femenino , Humanos , Japón , Masculino , Persona de Mediana Edad , Síndrome POEMS/mortalidad , Estudios Retrospectivos , Análisis de Supervivencia , Acondicionamiento Pretrasplante/métodos , Trasplante Autólogo/mortalidad , Resultado del TratamientoRESUMEN
PURPOSE OF REVIEW: Eosinophilic otitis media (EOM) is a refractory disease characterized by the accumulation of eosinophils in middle ear effusion and mucosa. We summarize current knowledge regarding the clinical characteristics and management of EOM. Although eosinophil activation in inflamed foci is involved in the pathogenesis of EOM, little is known about the fate of the eosinophils and aftermath of their cell death. We discuss the possibility that eosinophils undergo non-apoptotic cell death that worsens tissue damage and increases effusion viscosity. RECENT FINDINGS: Unlike chronic otitis media, EOM is strongly associated with an allergic background. Corticosteroids are currently the only effective pharmacological treatment, and surgical intervention is often required. Mucosal eosinophils infiltrate extensively into the middle ear cavity where they are stimulated by locally produced activators including interleukin-5 and eotaxin. The eosinophils undergo cytolysis in the effusion, which represents a major fate of activated eosinophils in vivo. Recent data revealed cytolysis could be renamed as extracellular trap cell death (ETosis). ETosis represents suicidal cell death involving total cell degranulation and development of sticky chromatin structures (extracellular traps (ETs)). The characteristics of eosinophil- and neutrophil-derived ET polymers might contribute to the difference in viscosity of secretions between EOM and common chronic otitis media. The extracellular products remaining after eosinophil ETosis are an important aspect of EOM pathology. The concept of ETosis also has novel implications for potential therapeutic modalities in various eosinophilic disorders.
Asunto(s)
Eosinófilos/inmunología , Trampas Extracelulares/inmunología , Otitis Media/inmunología , Animales , Muerte Celular , HumanosRESUMEN
BACKGROUND: Activated human eosinophils, as well as neutrophils, can release extracellular chromatin to form DNA traps through cytolytic extracellular trap cell death (ETosis). Although formations of neutrophil DNA traps are recognized in patients with various inflammatory conditions, neither the presence of ETosis-derived eosinophil DNA traps in human allergic diseases nor the characteristics of these DNA traps have been studied. OBJECTIVE: We investigated the presence of ETosis-derived DNA traps in eosinophil-rich sinus and ear secretions and the functional attributes of ETosis DNA traps. METHODS: Eosinophil-rich secretions obtained from patients with eosinophilic chronic rhinosinusitis and eosinophilic otitis media were studied microscopically. In vitro studies of ETosis and DNA trap formation used blood-derived eosinophils and neutrophils, and studies of the binding capacities of DNA traps used labeled bacteria and fluorescent microbeads. Stabilities of DNA traps were evaluated by using fluorescence microscopy. RESULTS: Abundant nuclear histone H1-bearing DNA traps formed in vivo in the eosinophilic secretions and contributed to their increased viscosity. In vitro, after brief shear flow, eosinophil ETosis-elicited DNA traps assembled to form stable aggregates. Eosinophil DNA traps entrapped bacteria and fungi and, through hydrophobic interactions, microbeads. In comparison with neutrophil-derived DNA traps, eosinophil DNA traps ultrastructurally exhibited thicker fibers with globular structures and were less susceptible to leukocyte-derived proteolytic degradation, likely because of the lesser protease activities of eosinophils. CONCLUSIONS: In human allergic diseases local cytolysis of eosinophils not only releases free eosinophil granules but also generates nuclear-derived DNA traps that are major extracellular structural components within eosinophil-rich secretions.
Asunto(s)
Trampas Extracelulares/inmunología , Candida albicans , Muerte Celular , Eosinofilia/inmunología , Eosinófilos/inmunología , Escherichia coli , Humanos , Mucinas/inmunología , Neutrófilos/inmunología , Péptido Hidrolasas/inmunología , Rinitis/inmunología , Sinusitis/inmunología , Staphylococcus aureusRESUMEN
Quality management systems are the tools that document the processes and responsibilities to achieve quality policies and objectives. Recently, increasing numbers of clinical laboratories have been certified for ISO 15189, an international certification for hospital laboratories. However, our laboratory remains in the preparation process. Major obstacles in our hospital are the tight budget and the timing of introducing the ISO 15189 system because of the old equipment in our laboratory. To overcome these problems, we have made efforts including study workshops with invited lecturers with expertise, joining the prefectural work- shop for clinical technicians. We have also started to prepare standard operational procedures for each la- boratory test. As the preparation advances, it has become clear that gaining the understanding of the signifi- cance of ISO 15189 of hospital executives is indispensable, especially in respect to funding. It is our respon- sibility to achieve standardized and improved laboratory examinations, in order to contribute to high-quality medical care, research, and education. Achieving the certification for ISO 15189 offers a great opportunity to improve our skills in laboratory medicine.
Asunto(s)
Certificación , Laboratorios de Hospital , Acreditación , Servicios de Laboratorio Clínico , Laboratorios de Hospital/normas , Control de CalidadRESUMEN
Hemophagocytic syndrome (HPS) is frequently associated with hematopoietic stem cell transplantation and is treated with some benefit derived from TNF-α inhibitors. However, the mechanisms of how HPS occurs and how a TNF-α inhibitor exerts some benefit to HPS management have remained unclear. We evaluated the effect of toll-like receptor (TLR) ligands, especially focusing on cytosine-phosphorothionate-guanine oligodeoxynucleotide (CpG), a TLR9 ligand, on HPS in mice that underwent transplantation with syngeneic or allogeneic bone marrow (BM) cells (Syn-BMT, Allo-BMT), or with allogeneic BM cells plus splenocytes to promote graft-versus-host disease (GVHD mice). Hemophagocytosis was a common feature early after all BMT, but it subsided in Syn-BMT and Allo-BMT mice. In GVHD mice, however, hemophagocytosis persisted and was accompanied by upregulated production of IFN-γ but not TNF-α, and it was suppressed by blockade of IFN-γ but not TNF-α. A single injection of the TLR9 ligand CpG promoted HPS in all BMT mice and was lethal in GVHD mice, accompanied by greatly upregulated production of TNF-α, IL-6, and IFN-γ. Blocking of TNF-α, but not IL-6 or IFN-γ, suppressed CpG-induced HPS in all BMT mice and rescued GVHD mice from CpG-induced mortality. Thus, TLR9 signaling mediates TNF-α-driven HPS in BMT mice and is effectively treated through TNF-α inhibition.
Asunto(s)
Trasplante de Médula Ósea/métodos , Linfohistiocitosis Hemofagocítica/inmunología , Oligodesoxirribonucleótidos/farmacología , Receptor Toll-Like 9/inmunología , Factor de Necrosis Tumoral alfa/inmunología , Animales , Anticuerpos Monoclonales/farmacología , Células de la Médula Ósea/citología , Células de la Médula Ósea/inmunología , Trasplante de Médula Ósea/efectos adversos , Islas de CpG/inmunología , Etanercept/farmacología , Rayos gamma , Regulación de la Expresión Génica , Enfermedad Injerto contra Huésped/inmunología , Enfermedad Injerto contra Huésped/patología , Interferón gamma/antagonistas & inhibidores , Interferón gamma/genética , Interferón gamma/inmunología , Interleucina-6/genética , Interleucina-6/inmunología , Linfocitos/citología , Linfocitos/inmunología , Linfohistiocitosis Hemofagocítica/etiología , Linfohistiocitosis Hemofagocítica/patología , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Ratones Noqueados , Oligodesoxirribonucleótidos/antagonistas & inhibidores , Transducción de Señal , Receptor Toll-Like 9/genética , Trasplante Homólogo , Trasplante Isogénico , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Factor de Necrosis Tumoral alfa/genética , Irradiación Corporal TotalRESUMEN
Hepatocyte growth factor (HGF), originally identified as a potent mitogen for mature hepatocytes, is now recognized as a humoral mediator in inflammatory and immune responses. Previous studies indicated that HGF negatively regulated allergic airway inflammation. In view of eosinophils playing a role in the pathogenesis of asthma, especially in airway remodeling as a rich source of pro-fibrogenic mediators, the effects of HGF on the different types of eosinophil secretory functions were examined in this study. We found that HGF significantly inhibited IL-5-induced secretion of TGF-ß and VEGF from human eosinophils. The inhibitory effect is not associated with TGF-ß transcription; rather, it is associated with ultrastructural granule emptying and loss of intracellular TGF-ß contents, indicating HGF inhibits the process of piecemeal degranulation. The effect of HGF on extracellular trap cell death (ETosis) that mediates cytolytic degranulation was also investigated; however, immobilized IgG- or phorbol myristate acetate-induced ETosis was only minimally attenuated by HGF. These results reveal the effect of HGF on the distinct pathways of eosinophil secretory functions and also provide novel insights into the role of HGF in the pathogenesis of allergic inflammation.
Asunto(s)
Eosinófilos/metabolismo , Factor de Crecimiento de Hepatocito/farmacología , Vesículas Secretoras/metabolismo , Eosinófilos/ultraestructura , Femenino , Humanos , Interleucina-5/metabolismo , Masculino , Vesículas Secretoras/ultraestructura , Factor de Crecimiento Transformador beta/metabolismo , Factor A de Crecimiento Endotelial Vascular/metabolismoRESUMEN
The outcomes of allogeneic hematopoietic cell transplantation (HSCT) in patients with biphenotypic acute leukemia (BAL) remain unclear. We retrospectively analyzed the outcomes of HSCT in BAL patients in Japan in comparison to acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) using the registration data from a nationwide database. The data of 90, 5371, and 3301 patients with BAL, AML, and ALL, respectively, were included in the analysis. The median follow-up period was 1481.5 days (range: 05556). The 5-year overall survival (OS) of the BAL, AML, and ALL patients were 39.6, 41.8, and 42.0 %, respectively (BAL vs. AML, P = 0.98 BAL vs. ALL, P = 0.77). A multivariate analysis revealed that, in comparison to BAL, AML with a better-risk karyotype was associated with superior OS. An analysis of the prognostic factors of BAL patients showed that OS was significantly longer in patients who were in their first complete remission in comparison to patients who were not in remission. Our data suggest that HSCT is an effective treatment for BAL patients, regardless of the presence of any known poor prognostic factors other than a non-remission status.
Asunto(s)
Trasplante de Células Madre Hematopoyéticas/tendencias , Leucemia Bifenotípica Aguda/diagnóstico , Leucemia Bifenotípica Aguda/terapia , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Estudios de Seguimiento , Humanos , Leucemia Bifenotípica Aguda/mortalidad , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Tasa de Supervivencia/tendencias , Trasplante Homólogo/tendencias , Resultado del Tratamiento , Adulto JovenRESUMEN
Previous studies have repeatedly reported that increasing age is a significant risk factor for worse outcomes after allogeneic hematopoietic stem cell transplantation (allo-HSCT) among patients with acute myeloid leukemia (AML). However, more recent studies reported conflicting results regarding the association between age and outcomes in elderly patients. Therefore, we conducted a large-scale, nationwide retrospective study to examine the impact of age on outcomes of allo-HSCT with reduced intensity conditioning (RIC) for AML patients who were older than 50 years. Of the 757 patients, 89 patients (11.8%) were 50-54, 249 patients (32.9%) were 55-59, 301 patients (39.8%) were 60-64 and 118 patients (15.6%) were ≥65 years old. The 3-year overall survival (OS) (47.8, 45.2, 37.9, and 36.6% for patients aged 50-54, 55-59, 60-64, and ≥65 years, respectively, P = 0.24) and nonrelapse mortality (NRM) (24.0, 22.8, 29.2, and 27.6% for patients aged 50-54, 55-59, 60-64, and ≥65 years, respectively, P = 0.49) were not significantly different among the four age groups. Multivariate analysis revealed that increased age had no significant effect on OS or NRM after adjusting for covariates. These results suggested that advanced patient age is not a contraindication for RIC allo-HSCT in elderly AML patients.
Asunto(s)
Trasplante de Células Madre Hematopoyéticas/métodos , Leucemia Mieloide Aguda/terapia , Acondicionamiento Pretrasplante/métodos , Factores de Edad , Anciano , Supervivencia sin Enfermedad , Femenino , Humanos , Leucemia Mieloide Aguda/mortalidad , Masculino , Persona de Mediana Edad , Recurrencia , Estudios Retrospectivos , Trasplante HomólogoRESUMEN
The traditional paradigm of eosinophils as end-stage damaging cells has mainly relied on their release of cytotoxic proteins. Cytokine-induced cell survival and secretion of granular contents from tissue-dwelling eosinophil are thought to be important mechanisms for eosinophilic inflammatory disorders, although the occurrence of cytolysis and its products (i.e., free extracellular granules) has been observed in affected lesions. Recent evidence indicates that activated eosinophils can exhibit a non-apoptotic cell death pathway, namely extracellular trap cell death (ETosis) that mediates the eosinophil cytolytic degranulation. Here, we discuss the current concept of eosinophil ETosis which provides a new look at eosinophilic inflammation. Lessons from eosinophilic chronic rhinosinusitis revealed that ETosis-derived DNA traps, composed of stable web-like chromatin, contribute to the properties of highly viscous eosinophilic mucin and impairments in its clearance. Intact granules entrapped in DNA traps are causing long-lasting inflammation but also might have immunoregulatory roles. Eosinophils possess a way to have post-postmortem impacts on innate immunity, local immune response, sterile inflammation, and tissue damage.
Asunto(s)
Eosinófilos/inmunología , Eosinófilos/patología , Trampas Extracelulares/inmunología , Inflamación/inmunología , Humanos , Inflamación/patologíaRESUMEN
BACKGROUND: A number of outbreaks caused by Bacillus species have been reported to date. Outbreaks reported in the last decade have predominantly arisen in Japanese hospitals. AIM: To elucidate factors contributing to these real or pseudo outbreaks by Bacillus species, and to evaluate the rate of Bacillus species-positive blood culture samples in Japan. METHODS: A systematic review of the literature was performed. Reports including data on outbreaks caused by Bacillus species were searched for in PubMed, Google Scholar and Evidence-based Medicine BMJ from inception through 10 Aug 2014. Japanese nationwide data on bacteriological tests were collected from Japan Nosocomial Infections Surveillance. Regional bacteriological data for Akita prefecture were collected using the Akita Regional Network for Infection Monitoring/Control System. FINDINGS: Contamination of reusable towels was suspected as a cause for the high rate of Bacillus-positive blood cultures in Japan. The rate of Bacillus species in blood cultures was much higher in Japan than in reports from other countries. CONCLUSIONS: The high contamination rate of blood culture samples by Bacillus species in Japan is a matter of concern for infection control and medical treatment. Bacteriological investigation of reusable towels should be considered in hospitals with a high frequency of Bacillus-positive blood cultures.
Asunto(s)
Infecciones por Bacillaceae/etiología , Bacillus/aislamiento & purificación , Infección Hospitalaria/microbiología , Infección Hospitalaria/etiología , Brotes de Enfermedades , Hospitales , Humanos , Control de Infecciones/métodos , JapónRESUMEN
With the development of medicine, the field of clinical laboratory medicine evolves rapidly, and it will be more specialized in the near future. Medical technologists are required to hone their skills and knowledge, in order to keep up with the evolution. In recent years, board certifications by several medical societies are considered to indicate the skills of medical technologists. The number of board-certified medical technologists in populated areas such as Tokyo, Kanagawa, Osaka, and Fukuoka is greater than in less populated areas such as Kyusyu and Tohoku. The rate of certified medical technologists among prefectures is the highest in Mie (10.1%), followed by Nagasaki (8.8%). Tokyo, Ishikawa, Kyoto, and Osaka have acquisition rates greater than 7%. In contrast, prefectures of Miyazaki, Kumamoto, Yamanashi, and Akita have low acquisition rates of less than 4%. Being certified is not only an opportunity for personal career advancement, but also a chance to improve the laboratory. More technologists are being certified in our laboratory, and we are encouraging a future increase in their number. However, there are some problems to be overcome. Assignment of competent staff and long-term and premeditated rotation are considered to be important for staff to find the work rewarding, and the laboratory to be trusted by physicians.
Asunto(s)
Personal de Laboratorio Clínico , Educación Médica Continua , Personal de Laboratorio Clínico/educación , Personal de Laboratorio Clínico/éticaRESUMEN
Pure red cell aplasia (PRCA) is a type of bone marrow failure syndrome (stem cell failure) and is characterized by severe normocytic, normochromic anemia associated with reticulocytopenia and the absence of erythroblasts in otherwise normal bone marrow. The acquired form of chronic PRCA may present as a primary hematological disease in the absence of any other diseases or secondary to thymoma, lymphoproliferative disorders, infections and collagen vascular diseases or after exposure to various drugs or chemicals. Thus, identifying the cause of PRCA is crucial for the optimal management of this disorder. Idiopathic PRCA and secondary PRCA refractory to treatment of the underlying diseases are both generally treated as an immune-mediated disorder. Most chronic PRCA patients successfully treated with immunosuppressants require maintenance immunosuppressive therapy. Refractoriness to induction immunosuppressive therapy and relapse of anemia may be risk factors for death in idiopathic, thymoma-associated and large granular lymphocyte leukemia-associated PRCA. The major causes of death are infections and organ failure. Standard treatment options for refractory and relapsed PRCA patients and the immunopathophysiology of acquired chronic PRCA merit further research.