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PURPOSE: Liquid biopsy of cyst fluid in brain tumors has not been extensively studied to date. The present study was performed to see whether diagnostic genetic alterations found in brain tumor tissue DNA could also be detected in cell-free DNA (cfDNA) of cyst fluid in cystic brain tumors. METHODS: Cyst fluid was obtained from 22 patients undergoing surgery for a cystic brain tumor with confirmed genetic alterations in tumor DNA. Pathological diagnoses based on WHO 2021 classification and diagnostic alterations in the tumor DNA, such as IDH1 R132H and TERT promoter mutation for oligodendrogliomas, were detected by Sanger sequencing. The same alterations were analyzed by both droplet digital PCR (ddPCR) and Sanger sequencing in cyst fluid cfDNA. Additionally, multiplex ligation-dependent probe amplification (MLPA) assays were performed to assess 1p/19q status, presence of CDKN2A loss, PTEN loss and EGFR amplification, to assess whether differentiating between astrocytomas and oligodendrogliomas and grading is possible from cyst fluid cfDNA. RESULTS: Twenty-five genetic alterations were found in 22 tumor samples. All (100%) alterations were detected in cyst fluid cfDNA by ddPCR. Twenty of the 25 (80%) alterations were also detected by Sanger sequencing of cyst fluid cfDNA. Variant allele frequency (VAF) in cyst fluid cfDNA was comparable to that of tumor DNA (R = 0.62, Pearson's correlation). MLPA was feasible in 11 out of 17 (65%) diffuse gliomas, with close correlation of results between tumor DNA and cyst fluid cfDNA. CONCLUSION: Cell-free DNA obtained from cyst fluid in cystic brain tumors is a reliable alternative to tumor DNA when diagnosing brain tumors.
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Neoplasias Encefálicas , Ácidos Nucleicos Libres de Células , Oligodendroglioma , Humanos , Oligodendroglioma/diagnóstico , Oligodendroglioma/genética , Oligodendroglioma/patología , Líquido Quístico , Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patología , Mutación , Reacción en Cadena de la Polimerasa Multiplex , ADNRESUMEN
Hypomethylating agent treatment for myeloid leukemia associated with Down syndrome (ML-DS) has been scarcely reported. Herein, we collected information on azacitidine treatment for ML-DS in Japan. Forty-eight cycles of azacitidine treatment were performed for 12 patients, including 11 relapsed or refractory (R/R) patients. In 40 cycles, azacitidine was used as monotherapy. No azacitidine-related death was observed. One cycle concurrently administered with methotrexate-based intrathecal therapy was discontinued due to toxicities. Only 4 of the 19 cycles given in non-remission achieved complete or partial remission. In conclusion, although most toxicities were acceptable, azacitidine monotherapy might be insufficient for R/R ML-DS cases.
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BACKGROUND: Extracellular vesicles (EVs) have received considerable attention as ideal biomarkers for kidney diseases. Most reports have focused on urinary EVs, that are mainly derived from the cells in the urinary tract. However, the detection and the application of kidney-derived EVs in plasma remains uncertain. METHODS: We examined the kidney-derived small EVs (sEVs) in plasma that were supposedly released from renal mesangial and glomerular endothelial cells, using clinical samples from healthy controls and patients with kidney transplants. Plasma from healthy controls underwent ultracentrifugation, followed by on-bead flow cytometry, targeting α8 integrin, an antigen-specific to mesangial cells. To confirm the presence of kidney-derived sEVs in peripheral blood, plasma from ABO-incompatible kidney transplant recipients was ultracentrifuged, followed by western blotting for donor blood type antigens. RESULTS: Immunohistochemistry and immunoelectron microscopy confirmed α8 integrin expression in kidney mesangial cells and their sEVs. The CD9-α8 integrin double-positive sEVs were successfully detected using on-bead flow cytometry. Western blot analysis further revealed transplanted kidney-derived sEVs containing blood type B antigens in non-blood type B recipients, who had received kidneys from blood type B donors. Notably, a patient experiencing graft kidney loss exhibited diminished signals of sEVs containing donor blood type antigens. CONCLUSION: Our findings demonstrate the potential usefulness of kidney-derived sEVs in plasma in future research for kidney diseases.
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Vesículas Extracelulares , Trasplante de Riñón , Humanos , Vesículas Extracelulares/metabolismo , Masculino , Femenino , Persona de Mediana Edad , Adulto , Estudios de Casos y Controles , Células Mesangiales/metabolismo , Biomarcadores/sangre , Sistema del Grupo Sanguíneo ABO , Tetraspanina 29/metabolismo , Citometría de Flujo , Riñón , Células Endoteliales/metabolismo , Incompatibilidad de Grupos SanguíneosRESUMEN
Chimeric antigen receptor (CAR)-T cell therapy is among the most promising immunotherapies for hematological malignancies and can be used to treat myeloid malignancies in practice. However, developing CAR-T therapies for such diseases is particularly challenging due to the heterogeneity of target antigen expression across leukemic cells and patients, the difficulty in excluding on-target/off-target tumor effects, and the immunosuppressive tumor microenvironment. To date, various targets, including CD33, NKG2D, CD123, CLL-1, and CD7, have been actively studied for CAR-T cells, especially for acute myeloid leukemia (AML). Although no CAR-T cell products have been approved, several clinical trials have shown promising results, particularly for those targeting CLL-1 and CD123. Furthermore, new ideal targets and use of allogeneic or off-the-shelf CAR-T cell products are under investigation. Meanwhile, it remains unknown whether CAR-T therapy would be effective for other myeloid malignancies, including myelodysplastic syndromes and myeloproliferative diseases. This review discusses challenges in the development of CAR-T therapy for myeloid malignancies, especially for AML, from the perspectives of target antigen characteristics and disease-specific on-target/off-tumor toxicity. Moreover, it discusses the clinical development and prospects of CAR-T cells for these diseases.
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Inmunoterapia Adoptiva , Humanos , Inmunoterapia Adoptiva/métodos , Receptores Quiméricos de Antígenos/inmunología , Neoplasias Hematológicas/terapia , Neoplasias Hematológicas/inmunología , Leucemia Mieloide Aguda/terapia , Leucemia Mieloide Aguda/inmunologíaRESUMEN
BACKGROUND AND OBJECTIVES: Allergic transfusion reactions (ATRs) and febrile non-haemolytic transfusion reactions (FNHTRs) are common, although their mechanisms remain unclear. Immunoglobulin E (IgE)-mediated type I hypersensitivity may be involved in the pathogenesis of ATR. A basophil activation test (BAT) may help elucidate this process. MATERIALS AND METHODS: The BAT was based on peripheral blood samples from paediatric patients with a haematological or oncological disease and on samples of residual blood products transfused in each case. Dasatinib was used to evaluate whether basophil activation was mediated by an IgE-dependent pathway. RESULTS: Twenty-seven patients with and 19 patients without ATR/FNHTR were included in this study, respectively. The median BAT values associated with ATR- (n = 41) and FNHTR-causing (n = 5) blood products were 22.1% (range = 6.1%-77.0%) and 27.8% (range = 15.2%-47.8%), respectively, which were higher than the median value of 8.5% (range = 1.1%-40.9%) observed in blood products without a transfusion reaction. Dasatinib suppressed basophil activity. BAT values were comparable in patients with ATR regardless of severity. Meanwhile, BAT values analysed with blood products non-causal for ATR/FNHTR were higher in patients with ATR/FNHTR than in those without. CONCLUSION: The IgE-mediated type I hypersensitivity may be involved in the pathogenesis of ATR and FNHTR. BAT analyses may help elucidate the underlying mechanisms and identify patients at risk.
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Hipersensibilidad Inmediata , Hipersensibilidad , Reacción a la Transfusión , Humanos , Niño , Prueba de Desgranulación de los Basófilos , Dasatinib , Hipersensibilidad/complicaciones , Reacción a la Transfusión/etiología , Hipersensibilidad Inmediata/complicaciones , Basófilos , Inmunoglobulina ERESUMEN
Thrombocytopenia is a common abnormality encountered in the neonatal period, and immature platelet fraction (IPF) may be an informative indicator of thrombopoiesis; however, data on IPF in neonates are scarce. To define reference intervals (RIs) and factors affecting IPF in neonates, we measured the IPF of 533 consecutive neonates. With a multiple regression analysis of 330 newborns with normal platelet counts at birth, premature delivery, neonatal asphyxia, intrauterine infection, chromosomal abnormalities, and respiratory disorders were identified as independent factors for IPF%. The RIs of IPF% and absolute IPF value in neonates were determined to be 1.3% to 5.7% and 3.2 to 14.5×10 9 /L, respectively. On day 14 after birth, IPF% increased to twice the value at birth and thereafter returned to the previous value on day 28. Reticulocyte counts, in contrast, were the lowest at day 14. IPF% was increased in 16 thrombocytopenic patients with various clinical conditions, especially those with immune-mediated thrombocytopenia. IPF in neonates may be evaluated essentially based on the same RIs as in adults, although some precautions must be taken when evaluating IPF in neonates in the first 2 weeks of life. IPF may be useful for evaluating thrombopoiesis and thrombocytopenia in neonates.
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Púrpura Trombocitopénica Idiopática , Trombocitopenia , Adulto , Humanos , Recién Nacido , Recuento de Plaquetas , Cinética , PlaquetasRESUMEN
BACKGROUND: The treatment of membranous nephropathy involves a combination of conservative approaches, steroids, and immunosuppressive agents. Infection is an adverse effect of these treatments and its incidence is a critical issue for patients with membranous nephropathy, as many of them are older adults. However, the incidence of infections remains unclear; hence, this study investigated this issue using data from a large Japanese clinical claims database. METHODS: From a database of patients with chronic kidney disease (n = 924,238), those diagnosed with membranous nephropathy from April 2008 to August 2021 with a history of one or more prescriptions and undergoing medical care were included. Patients who had undergone kidney replacement therapy were excluded. Patients were divided into three groups based on their prescriptions after diagnosis: prednisolone(PSL), who received steroids; PSL + IS, who were prescribed steroids and immunosuppressive agents; and C, who were treated without steroid or immunosuppressive agent use. The primary outcome was death or the initiation of kidney replacement therapy. The secondary outcome was death or hospitalization due to infection. Infectious diseases such as sepsis, pneumonia, urinary tract infections, cellulitis, cytomegalovirus infection, colitis, or hepatitis were defined as infections. Hazard ratios were expressed using group C as a reference. RESULTS: Of 1,642 patients, the incidence of the primary outcome occurred in 62/460 individuals in the PSL group, 81/635 individuals in the PSL + IS group, and 47/547 individuals in the C group. The Kaplan-Meier survival curve showed no significant differences (P = 0.088). The incidence of secondary outcomes occurred in 80/460 individuals, 102/635 individuals, and 37/547 individuals in the PSL, PSL + IS, and C groups, respectively. The incidence of secondary outcomes was significantly higher in the PSL group (hazard ratio [HR] 2.43 [95% confidence interval [CI] 1.64-3.62, P < 0.01]) and PSL + IS group (HR 2.23 [95% CI 1.51-3.30, P < 0.01]). CONCLUSIONS: The outcome of membranous nephropathy was not completely satisfactory. Patients who use steroids and immunosuppressive agents have a high incidence of infection and may require close monitoring during the course of treatment.High-efficacy treatment with a low incidence of infections is desirable. The significance of this study lies in the fact that the impressions of membranous nephropathy, which have been recognized as tacit knowledge, were quantified using a clinical database.
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Glomerulonefritis Membranosa , Insuficiencia Renal Crónica , Humanos , Pueblos del Este de Asia , Glomerulonefritis Membranosa/tratamiento farmacológico , Glomerulonefritis Membranosa/epidemiología , Glomerulonefritis Membranosa/complicaciones , Inmunosupresores/uso terapéutico , Incidencia , Pronóstico , Insuficiencia Renal Crónica/complicaciones , Esteroides/uso terapéuticoRESUMEN
Breast cancer is a complex heterogeneous disease with unique molecular subtypes, which limits the development of optimized treatment strategies for each subtype. Cancer gene therapy and potential therapeutics for advanced/refractory cancers can be promising for breast cancer. Combining tumor-tropic lipid nanoparticles (LNPs) and inducible caspase-9 (iC9) mRNA, we aimed to develop a novel treatment strategy for refractory breast cancer. LNP's anti-tumor effects were tested in vitro in three breast cancer cell lines: MDA-MB231, SKBR3, and MCF-7. Tumor cells were treated with LNPs encapsulated with eGFP or iC9 mRNA and chemical inducers of dimerization (CID). Apoptosis-related genes were evaluated by reverse transcriptase quantitative PCR. LNPs could efficiently deliver encapsulated GFP mRNA to all three cancer cell lines (>80% GFP expression. in target cells). Furthermore, LNPs encapsulated with iC9 mRNA (iC9-LNPs) and CID showed cytotoxic activity against all cancer cell lines in vitro. Interestingly, susceptibility to iC9 gene therapy was heterogeneous among cancer cell lines. iC9-LNPs with CID-induced potent cytotoxic effects against SKBR3 and MDA-MB231 cells, but only a mild cytotoxic effect on MCF7 cells. Quantification of apoptosis-related genes suggested that a high BAX/Bcl-2 ratio might be associated with iC9-LNP + CID susceptibility. Thus, cancer gene therapy using iC9-LNPs and CID could be a promising alternative for the treatment of breast cancers, especially for aggressive breast cancers.
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Antineoplásicos , Neoplasias de la Mama , Nanopartículas , Humanos , Femenino , Caspasa 9/genética , Caspasa 9/metabolismo , Neoplasias de la Mama/genética , Neoplasias de la Mama/terapia , ARN Mensajero/genética , Nanopartículas/químicaRESUMEN
Acute lymphoblastic leukemia (ALL) is the most common cancer during childhood, and some high-risk patients with ALL require hematopoietic stem cell transplantation (HSCT). Mainly due to small patient numbers, studies focusing specifically on children and adolescents with T-cell ALL (T-ALL) are limited. Using a nationwide registry, we retrospectively analyzed data from patients under 20 years old who underwent their first HSCT for T-ALL between 2000 and 2018. As a result, total 484 patients were included, and their median follow-up period was 6.9 years after HSCT for survivors. While patients receiving HSCT at first complete remission (CR) showed relatively good 5-year leukemia free survival (5yLFS, 73.5%), once relapse occurred, their prognosis was much worse (44.4%) even if they attained second remission again (p < 0.001). Among patients receiving HSCT at CR1, grade II-IV acute graft versus host disease was associated with worse overall and LFS than grade 0-I (5yLFS 69.5% vs. 82.1%, p = 0.026) mainly due to high non-relapse mortality. Among those patients, patients receiving related bone marrow transplantation, unrelated bone marrow transplantation, or unrelated cord blood transplantation showed similar survival (5yLFS, 73.2%, 76.3%, and 77.0%, respectively). For patients undergoing cord blood transplantation at CR1, total-body irradiation-based myeloablative conditioning was associated with better 5yLFS than other conditioning regimens (85.4% vs. 62.2%, p = 0.044), as it reduced the risk of relapse. These results indicate that relapsed patients have much less chance of cure, and that identifying patients who require HSCT for cure and offering them HSCT with optimal settings during CR1 are crucial for children and adolescents with T-ALL.
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Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Leucemia-Linfoma Linfoblástico de Células Precursoras , Leucemia-Linfoma Linfoblástico de Células T Precursoras , Adolescente , Adulto , Niño , Enfermedad Injerto contra Huésped/complicaciones , Trasplante de Células Madre Hematopoyéticas/métodos , Humanos , Leucemia-Linfoma Linfoblástico de Células Precursoras/etiología , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Leucemia-Linfoma Linfoblástico de Células T Precursoras/terapia , Pronóstico , Recurrencia , Estudios Retrospectivos , Linfocitos T , Acondicionamiento Pretrasplante/métodos , Trasplante Homólogo , Adulto JovenRESUMEN
BACKGROUND: Allergic transfusion reactions (ATRs) manifest frequently as transfusion reactions, and their onset may be related to a patient's allergic predisposition. Moreover, although pediatric patients with hematological/oncological disease are more susceptible to ATRs, the relationship between allergic predisposition and ATRs remains to be fully clarified. STUDY DESIGN AND METHODS: Patients who were diagnosed with pediatric hematological/oncological disease and received transfusion at the study institutions were included. We determined patient background information related to their allergy history, measured the levels of allergen-specific immunoglobulin E (IgE) using sera obtained on diagnosis, and analyzed their associations with ATR onset. RESULTS: Of the 363 patients analyzed, 144 developed ATRs. Multivariate analysis identified cases with high basophils in the peripheral blood, and Dermatophagoides pteronyssinus- and egg white-specific IgEs were involved in the development of ATR in all age groups. Meanwhile, a history of food allergies, and positivity for Japanese cypress- and D. pteronyssinus-specific IgEs were risk factors for developing ATRs in the <5 years age group. Moreover, patients aged 5-<10 years with a history of asthma, allergic rhinitis, pollinosis, or atopic dermatitis, and those aged ≥10 years with positivity for dog dander-specific IgE were at risk for developing ATRs. CONCLUSION: The allergic constitution of patients plays a role in ATR onset even in pediatric hematological/oncological diseases. Therefore, advance confirmation of a patient's allergic constitution may partly predict the onset of ATRs. However, since multiple allergic predispositions within complex mechanisms may be involved in the onset of ATRs, further verification is required.
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Hipersensibilidad , Reacción a la Transfusión , Animales , Basófilos , Niño , Susceptibilidad a Enfermedades/complicaciones , Perros , Humanos , Hipersensibilidad/etiología , Inmunoglobulina E/análisis , Factores de Riesgo , Reacción a la Transfusión/complicacionesRESUMEN
Although skin complications are common adverse events from tyrosine kinase inhibitors (TKIs) for the treatment of chronic myeloid leukemia (CML), no reports have focused on skin and soft tissue infections (SSTIs) associated with TKI use. We herein present five episodes of SSTIs in three CML patients under dasatinib treatment. All patients were adolescents and had been receiving dasatinib for more than 4 years. In contrast, none of 41 adult CML patients experienced SSTIs in a retrospective analysis. Our findings suggest that long-term dasatinib treatment in adolescent patients may be associated with the increased risk of SSTIs.
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Leucemia Mielógena Crónica BCR-ABL Positiva , Infecciones de los Tejidos Blandos , Adolescente , Adulto , Dasatinib/efectos adversos , Humanos , Mesilato de Imatinib/efectos adversos , Leucemia Mielógena Crónica BCR-ABL Positiva/tratamiento farmacológico , Inhibidores de Proteínas Quinasas/efectos adversos , Pirimidinas/efectos adversos , Estudios Retrospectivos , Infecciones de los Tejidos Blandos/inducido químicamenteRESUMEN
Neurenteric cyst (NC) shows benign histopathology and rarely demonstrate malignant transformation. We herein describe a case of NC that exhibited malignant transformation. A 65-year-old female presented with gait disturbance due to compression by a cystic mass on the dorsal surface of the medulla oblongata. Partial resection was performed twice, leading to improvement of her symptoms. Two years after the second surgery, gadolinium-perfused T1-weighted magnetic resonance imaging revealed an invasive lesion with contrast enhancement at the trigone of the left lateral ventricle for which partial resection followed by radiotherapy was performed. However, mass regrowth was observed, with the patient eventually succumbing to her disease 11 months after her third surgery. Histopathological analyses of the first and second surgical specimens identified pseudostratified cuboidal epithelial cells, with no nuclear or cellular atypia resembling gastrointestinal mucosa, lining the inner surface of the cystic wall. Based on these findings the lesion was diagnosed as NC. The third surgical specimen exhibited apparent malignant features of the epithelial cells with elongated and hyperchromatic nuclei, several mitotic figures, small necrotic foci, and a patternless or sheet-like arrangement. Based on these findings, the lesion was diagnosed as NC with malignant transformation. Next-generation sequencing revealed KRAS p.G12D mutation in all specimens. Additionally, the third surgical specimen harbored the following 12 de novo gene alterations: ARID1A loss, BAP1 p.F170L, CDKN1B loss, CDKN2A loss, CDKN2B loss, FLCN loss, PTCH1 loss, PTEN loss, PTPRD loss, SUFU loss, TP53 loss, and TSC1 loss. The aforementioned results suggest that KRAS mutation is associated with the development of the NC, and that the additional gene alterations contribute to malignant transformation of the NC.
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Defectos del Tubo Neural , Humanos , Femenino , Anciano , Defectos del Tubo Neural/genética , Defectos del Tubo Neural/patología , Transformación Celular Neoplásica/genética , Transformación Celular Neoplásica/patología , Mutación , Proteínas Proto-Oncogénicas p21(ras)/genéticaRESUMEN
The selective provocative test (SPT) under local anesthesia aids in protecting against ischemic complications during endovascular treatment. However, the use of this test under general anesthesia is not well described. Herein, we present a case of a 51-year-old man with a ruptured fusiform aneurysm in the middle cerebral artery M4 segment, which was thought to possibly supply the motor cortex. Internal trapping of the affected vessel and aneurysm by endovascular intervention was successfully performed after SPT using transcranial motor evoked potential (MEP) monitoring under general anesthesia. Transcranial MEP is suitable for neurological assessment during SPT under general anesthesia.
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Aneurisma Infectado , Aneurisma Intracraneal , Anestesia General , Potenciales Evocados Motores/fisiología , Humanos , Aneurisma Intracraneal/diagnóstico por imagen , Aneurisma Intracraneal/cirugía , Masculino , Persona de Mediana Edad , Arteria Cerebral Media , Monitoreo IntraoperatorioRESUMEN
RATIONALE: Myofibroblasts have roles in tissue repair following damage associated with ischemia, aging, and inflammation and also promote fibrosis and tissue stiffening, causing organ dysfunction. One source of myofibroblasts is mesenchymal stromal/stem cells that exist as resident fibroblasts in multiple tissues. We previously identified meflin (mesenchymal stromal cell- and fibroblast-expressing Linx paralogue), a glycosylphosphatidylinositol-anchored membrane protein, as a specific marker of mesenchymal stromal/stem cells and a regulator of their undifferentiated state. The roles of meflin in the development of heart disease, however, have not been investigated. OBJECTIVE: We examined the expression of meflin in the heart and its involvement in cardiac repair after ischemia, fibrosis, and the development of heart failure. METHODS AND RESULTS: We found that meflin has an inhibitory role in myofibroblast differentiation of cultured mesenchymal stromal/stem cells. Meflin expression was downregulated by stimulation with TGF (transforming growth factor)-ß, substrate stiffness, hypoxia, and aging. Histological analysis revealed that meflin-positive fibroblastic cells and their lineage cells proliferated in the hearts after acute myocardial infarction and pressure-overload heart failure mouse models. Analysis of meflin knockout mice revealed that meflin is essential for the increase in the number of cells that highly express type I collagen in the heart walls after myocardial infarction induction. When subjected to pressure overload by transverse aortic constriction, meflin knockout mice developed marked cardiac interstitial fibrosis with defective compensation mechanisms. Analysis with atomic force microscopy and hemodynamic catheterization revealed that meflin knockout mice developed stiff failing hearts with diastolic dysfunction. Mechanistically, we found that meflin interacts with bone morphogenetic protein 7, an antifibrotic cytokine that counteracts the action of TGF-ß and augments its intracellular signaling. CONCLUSIONS: These data suggested that meflin is involved in cardiac tissue repair after injury and has an inhibitory role in myofibroblast differentiation of cardiac fibroblastic cells and the development of cardiac fibrosis.
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Diástole , Inmunoglobulinas/metabolismo , Células Madre Mesenquimatosas/metabolismo , Infarto del Miocardio/metabolismo , Miofibroblastos/metabolismo , Regeneración , Animales , Células CHO , Células Cultivadas , Colágeno/genética , Colágeno/metabolismo , Cricetinae , Cricetulus , Células HEK293 , Humanos , Inmunoglobulinas/genética , Metaloproteinasa 7 de la Matriz/metabolismo , Ratones , Ratones Endogámicos C57BL , Infarto del Miocardio/genética , Infarto del Miocardio/fisiopatología , Miofibroblastos/fisiología , Unión ProteicaRESUMEN
ABO-incompatible hematopoietic stem cell transplantations (HSCTs) are widely practiced; however, the delay in erythrocyte engraftment can be problematic. While erythrocyte engraftment is usually indicated by an increase in reticulocyte levels without the need for erythrocyte transfusions, the disappearance of recipient-derived anti-A/B isoagglutinin and detection of donor-derived A/B antigens can also be used as other parameters. We conducted a retrospective analysis of 68 ABO-incompatible HSCTs, focusing on major and bidirectional mismatch. We analyzed known clinical risk factors associated with delayed erythrocyte engraftment using the three parameters (disappearance of anti-A/B isoagglutinin in recipient, detection of donor-derived A/B antigen, and reticulocyte levels >1%). Although the three parameters were well correlated, the results showed heterogeneity when analyzing the associated risk factors for delayed erythrocyte engraftment. In the analysis of all cases, the requirement for an HLA-matched platelet transfusion was a common risk factor. Furthermore, erythrocyte engraftment was slower in adults than in children. In adults, cytomegalovirus antigenemia was a risk factor for two parameters; however, in children, underlying disease was a common risk factor for all parameters. There is a complex relationship between erythrocyte engraftment and various factors related to HSCTs. Our results suggest that greater accuracy is possible by using analysis methods other than the measurement of reticulocyte levels.
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Incompatibilidad de Grupos Sanguíneos , Trasplante de Células Madre Hematopoyéticas , Sistema del Grupo Sanguíneo ABO , Adulto , Niño , Eritrocitos , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Humanos , Estudios Retrospectivos , Factores de RiesgoRESUMEN
BACKGROUND: Acute kidney injury (AKI) is a complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Increasing severity of AKI is associated with an increased risk of death. However, the impact of AKI in patients with malignant versus nonmalignant disease has not been reported. We investigated the incidence of AKI within the first 100 days after allo-HSCT and the impact of AKI on both 3-year overall survival (OS) and cumulative incidence of death after allo-HSCT in all patients and in patients with/without malignant primary diseases. METHODS: We performed a retrospective analysis of 107 consecutive pediatric and young adult patients who received their first allo-HSCT. AKI was classified into three grades according to the Acute Kidney Injury Network classification system. RESULTS: The cumulative incidences of AKI stages 1-3, 2-3, and 3, at day 100 after allo-HSCT were 34.6% (95% confidence interval [CI], 25.7%-43.6%), 17.8% (95% CI, 11.2%-25.6%), and 3.7% (95% CI, 1.2%-8.6%), respectively. OS was reduced for patients with AKI compared with patients without AKI (60.4% vs. 79.6%, p = .038). The cumulative incidence of death in the AKI group with nonmalignant disease was significantly higher than that in the no-AKI group (44.4% vs. 0%, p = .003). CONCLUSION: AKI after allo-HSCT was not only a frequent event but also related to reduced OS. We recommend that all patients receiving allo-HSCT, especially patients with nonmalignant diseases, be closely monitored for AKI.
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Lesión Renal Aguda , Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Lesión Renal Aguda/epidemiología , Lesión Renal Aguda/etiología , Adolescente , Niño , Enfermedad Injerto contra Huésped/epidemiología , Enfermedad Injerto contra Huésped/etiología , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Humanos , Incidencia , Estudios Retrospectivos , Factores de Riesgo , Tasa de Supervivencia , Adulto JovenRESUMEN
Unilateral oculomotor nerve palsy, often caused by aneurysmal compression, is one of the decisive findings for confirming the site of a ruptured aneurysm. However, arterial compression can also cause unilateral oculomotor nerve palsy. Here, we present the case of a 59-year-old woman with a ruptured right internal carotid-posterior communicating artery aneurysm accompanied by contralateral oculomotor nerve palsy. The nerve was found to be compressed by the posterior cerebral artery and was isolated from the ruptured aneurysm. When confirming a ruptured aneurysm based on the evidence of unilateral oculomotor palsy, the arteries surrounding the nerve must be thoroughly assessed.
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Aneurisma Roto/complicaciones , Aneurisma Intracraneal/complicaciones , Enfermedades del Nervio Oculomotor/etiología , Arteria Cerebral Posterior/patología , Hemorragia Subaracnoidea/complicaciones , Femenino , Humanos , Persona de Mediana Edad , Hemorragia Subaracnoidea/congénitoRESUMEN
BACKGROUND: Accurate evaluation of kidney function before and after allogeneic hematopoietic stem cell transplantation (allo-HSCT) is important for both informed decision making and detection of chronic kidney disease. However, to the best of our knowledge, no report has evaluated the glomerular filtration rate (GFR) in pediatric patients who underwent HSCT using the gold standard GFR measurement, as well as inulin-based GFR (iGFR). METHODS: We assessed iGFR before and after allo-HSCT to evaluate the impact of allo-HSCT on GFR in a prospective cohort study of 17 pediatric patients. We also assessed the accuracy and bias of the values of estimated GFR (eGFR) calculated using serum creatinine (Cr), cystatin C (CysC), beta-2 microglobulin (ß2 MG), 24-h creatinine clearance (24hCcr), and the full chronic kidney disease in children (CKiD) index that combines Cr, CysC, and blood urea nitrogen-based equations with iGFR as a reference to identify the most reliable equation for GFR. RESULTS: There was no significant difference between the values before and after allo-HSCT. CKiD CysC-, 24hCcr-, and full CKiD-based values showed good within 30% (P30) accuracy (80.6%, 79.3%, and 80.6%, respectively), but only 24hCcr and full CKiD had good mean bias (8.5% and 8.9%, respectively) and narrow 95% limits of agreement (-32.2 to 52.7 mL/min/1.73 m2 and -29.3 to 47.4 mL/min/1.73 m2 , respectively) compared with the corresponding iGFR. CONCLUSION: There was no significant impact of allo-HSCT on GFR in our cohort. The most reliable equations for pediatric patients with allo-HSCT were eGFR-24hCcr and eGFR-full CKiD.
Asunto(s)
Biomarcadores/análisis , Tasa de Filtración Glomerular , Neoplasias Hematológicas/terapia , Trasplante de Células Madre Hematopoyéticas/métodos , Inulina/análisis , Riñón/fisiopatología , Adolescente , Niño , Preescolar , Creatinina/sangre , Cistatina C/sangre , Femenino , Estudios de Seguimiento , Neoplasias Hematológicas/patología , Humanos , Pruebas de Función Renal , Masculino , Pronóstico , Estudios ProspectivosRESUMEN
BACKGROUND AND OBJECTIVES: Plasma reduction in platelet concentrate (PC) products has been reported to prevent large volume load and transfusion-related adverse reactions (TRARs). However, volume reduction might be associated with a poor transfusion response because of a deterioration in platelet (PLT) quality. Because PLT quality control and transfusion responses for recently washed PCs using PLT additive solutions are superior, we investigated the clinical safety and transfusion efficacy of volume-reduced washed PCs in pediatric patients. MATERIALS AND METHODS: We prepared a simplified resuspended PC product (RPC) as a washed PC. Regular RPC (R-RPC) included equivalent volumes of bicarbonate Ringer's solution and anticoagulant citrate dextrose solution A (BRS-A) as the resuspension solution. Half RPC (H-RPC) was prepared by adding a half volume of BRS-A. Twenty-four pediatric patients were scheduled for transfusions with R-RPC and H-RPC up to 4 times. R-RPC was transfused 42 times into 24 patients. H-RPC was transfused 41 times into 23 patients. RESULTS: Neither product was observed to cause TRARs. Although the calculated PLT recovery for H-RPC was significantly reduced, the posttransfusion corrected count increment (24 h) did not differ. Moreover, similar results were observed for vital signs during transfusion. CONCLUSION: Volume-reduced washed PC can be transfused without causing TRARs, differences in vital signs, or inferior transfusion responses. Volume-reduced washed PC also provides the advantages of shortened transfusion times and reduced volume loads. Although a standard technique for stable resuspension is necessary, volume-reduced washed PC may be a beneficial option for children, including neonates, or individuals with cardiovascular or renal problems.
Asunto(s)
Plaquetas/metabolismo , Transfusión de Plaquetas/métodos , Adolescente , Adulto , Niño , Femenino , Humanos , Masculino , Resultado del Tratamiento , Adulto JovenRESUMEN
BACKGROUND: The optimal method for thyroid cancer screening in childhood cancer survivors (CCSs) who received radiation involving the thyroid gland is still debated. We describe a case series of ultrasound surveillance for thyroid tumor in CCSs in our institute. METHODS: We conducted thyroid tumor surveillance for CCSs with a history of radiation therapy involving the thyroid. The basic screening method was palpation. Thyroid ultrasound was also performed for patients who agreed after its benefits and risks were explained to them. We surveyed CCSs who visited the long-term follow-up outpatient clinic in our institution between October 2014 and September 2018. RESULTS: Of 82 CCSs who visited our institution during the study period, 44 were eligible for inclusion. None had a mass identified by palpation. Thyroid ultrasound was performed in 39 CCSs, and we identified thyroid nodules in 27. Four patients had a nodule with malignant echo features. Two of these cases received biopsies, and one patient was ultimately diagnosed with an early stage thyroid carcinoma. CONCLUSIONS: Childhood cancer survivors irradiated in the thyroid had a higher prevalence of thyroid nodules than the general population. Ultrasound screening contributed to early detection of impalpable thyroid cancer and enabled us to perform minimal surgery. Thus, ultrasound appears to be a useful option for secondary thyroid cancer screening. The thyroid tumor surveillance modality should be considered according to the individual case, and the patient must receive a clear explanation of the benefits and risks. These results could help doctors consider how to screen for secondary thyroid cancer.