RESUMO
BACKGROUND: The seasonal epidemic of Kawasaki disease (KD) in winter in Japan suggests that low vitamin D status may affect KD through the immune system. We aimed to evaluate the effect of vitamin D on the onset and clinical course of KD. METHODS: We conducted a case-control study to compare 25-hydroxyvitamin D (25(OH)D) levels in KD patients admitted to our hospital between March 2018 and June 2021, with those in healthy controls from published Japanese data. In patients with KD, we evaluated the association of 25(OH)D levels with intravenous immunoglobulin resistance and coronary artery lesions. RESULTS: We compared 290 controls and 86 age-group-adjusted patients with KD. The 25(OH)D levels in KD patients were lower than those in the controls (median: 17 vs. 29 ng/mL, P < 0.001). In winter, 25(OH)D levels in KD patients were lower than those in summer (median: 13 vs. 19 ng/mL). The adjusted odds ratios for the onset of KD were 4.9 (95% CI: 2.5-9.6) for vitamin D insufficiency (25(OH)D: 12-20 ng/mL) and 29.4 (95% CI: 12.5-78.2) for vitamin D deficiency (25(OH)D < 12 ng/mL). Among 110 KD patients, 25(OH)D levels at diagnosis of KD were not associated with intravenous immunoglobulin resistance or coronary artery lesions. CONCLUSIONS: The 25(OH)D levels in patients with KD were lower than those in the controls, especially in winter. Lower 25(OH)D levels in winter were associated with an increased risk of KD onset. It remains to be elucidated whether the observed association has a causal relationship.
Assuntos
Síndrome de Linfonodos Mucocutâneos , Deficiência de Vitamina D , Estudos de Casos e Controles , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Síndrome de Linfonodos Mucocutâneos/complicações , Síndrome de Linfonodos Mucocutâneos/tratamento farmacológico , Síndrome de Linfonodos Mucocutâneos/epidemiologia , Estações do Ano , Vitamina D , Deficiência de Vitamina D/complicações , Deficiência de Vitamina D/epidemiologia , VitaminasRESUMO
Post-transplant ES, which is often resistant to therapies, has seldom been described. This report describes a case of ES after UBMT for RCC. A five-yr-old boy developed RCC with no evidence of monosomy 7. Because no matching family donors were available for SCT and immunosuppressive therapy was ineffective, UBMT was performed when he was six yr old. The conditioning regimen included TAI (3 Gy) and administration of FLU, CY, and rabbit antithymocyte globulin. The recovery of blood cells was good. He displayed grade II acute GVHD involving only the skin. ES developed on day 66, with positive results for Epstein-Barr virus DNA and HHV 6. Cytopenia was resolved with treatment with RTX, GCV, an escalated dose of steroids, high-dose gammaglobulin, and romiplostim. No relapse has occurred since discontinuing steroids on day 177 and romiplostim on day 268. Post-SCT ES after UBMT is rare, and the risk factors and therapies are unclear. Prospective analysis and collection of cases from multiple centers are required for clarification.
Assuntos
Anemia Hemolítica Autoimune/etiologia , Transplante de Medula Óssea , Púrpura Trombocitopênica Idiopática/complicações , Púrpura Trombocitopênica Idiopática/terapia , Trombocitopenia/etiologia , Pré-Escolar , DNA/análise , DNA Viral/metabolismo , Herpesvirus Humano 4 , Humanos , Imunossupressores/efeitos adversos , Imunossupressores/uso terapêutico , Masculino , Estudos Prospectivos , Receptores Fc/química , Receptores Fc/uso terapêutico , Proteínas Recombinantes de Fusão/química , Proteínas Recombinantes de Fusão/uso terapêutico , Fatores de Risco , Esteroides/uso terapêutico , Trombopoetina/química , Trombopoetina/uso terapêutico , Fatores de Tempo , Resultado do Tratamento , gama-Globulinas/química , gama-Globulinas/uso terapêuticoRESUMO
BACKGROUND: NUT midline carcinoma (NMC) is recognized as a very rare tumor that most often occurs around the midline and shows NUT rearrangement. This tumor affects children and younger adults, progresses rapidly, and shows an extremely poor prognosis, even with intensive chemotherapy. Very few reports have described effective treatment for this tumor. METHODS: A 12-year-old girl with NMC was treated using cisplatin (CDDP), docetaxel, gemcitabine, pemetrexed, and vinorelbine. RESULTS: Imaging showed partial response with CDDP and docetaxel, and complete response with gemcitabine. After reexacerbation of the tumor, although partial response was achieved with vinorelbine, the patient died 89 weeks after onset because of reexacerbation. CONCLUSIONS: NMC is a very rare disease with poor prognosis. This study is the first to report response of NMC to gemcitabine and vinorelbine. The findings suggest that combination chemotherapies including CDDP, docetaxel, gemcitabine, and vinorelbine may be a choice in the treatment for NMC.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma de Células Escamosas/tratamento farmacológico , Proteínas Nucleares/genética , Proteínas de Fusão Oncogênica/genética , Neoplasias Torácicas/tratamento farmacológico , Antimetabólitos Antineoplásicos/uso terapêutico , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/genética , Criança , Cisplatino/uso terapêutico , Desoxicitidina/análogos & derivados , Desoxicitidina/uso terapêutico , Docetaxel , Evolução Fatal , Feminino , Humanos , Indução de Remissão , Taxoides/uso terapêutico , Neoplasias Torácicas/diagnóstico , Neoplasias Torácicas/genética , GencitabinaRESUMO
Haematopoietic stem-cell transplantation (HSCT)-associated thrombotic microangiopathy (HSCT-TMA) is a serious complication with high mortality. Accumulating evidence suggests that complement dysregulation is potentially involved in the development of HSCT-TMA. We retrospectively analysed the clinical characteristics and outcomes of thirteen paediatric patients who were diagnosed with atypical haemolytic uremic syndrome and treated with eculizumab to manage HSCT-TMA during post-marketing surveillance in Japan. The median time from HSCT to TMA was 31 days (Interquartile range, IQR;21-58) and the median doses of eculizumab was three (IQR;2-5). Seven patients (54%) were alive at the last follow-up while six died due to complications related to HSCT. Six of seven survivors initiated eculizumab after insufficient response to plasma therapy. Following eculizumab treatment, median platelet counts and LDH levels in all survivors significantly improved and renal function improved in 4/7 patients. All survivors possessed potential risk factors of complement overactivation. During the follow-up period after eculizumab discontinuation (median;111.5 days, IQR;95-555), no TMA recurrence was observed. In this analysis, eculizumab showed benefit in over half of this paediatric patient population. Ongoing clinical studies are expected to optimize the treatment regimen of terminal complement pathway inhibitor, and it may become a therapeutic option for paediatric HSCT-TMA in the future.
Assuntos
Anticorpos Monoclonais Humanizados , Transplante de Células-Tronco Hematopoéticas , Microangiopatias Trombóticas , Criança , Humanos , Japão , Estudos Retrospectivos , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Inativadores do Complemento/efeitos adversos , Microangiopatias Trombóticas/tratamento farmacológico , Microangiopatias Trombóticas/etiologia , Microangiopatias Trombóticas/diagnóstico , Vigilância de Produtos ComercializadosRESUMO
BACKGROUND: In children with intermediate-risk relapsed acute lymphoblastic leukemia (ALL), allogeneic hematopoietic stem cell transplantation (allo-HSCT) has markedly improved the outcome of patients with an unsatisfactory minimal residual disease (MRD) response. Total body irradiation (TBI), etoposide (ETP), and cyclophosphamide (CY) have been shown to be equivalent to or better than TBI + ETP for conditioning, so we hypothesized that even greater survival could be achieved due to recent advances in HSCT and supportive care. PROCEDURE: We prospectively analyzed the efficacy and safety of allo-HSCT with a unified conditioning regimen of TBI + ETP + CY in children with intermediate-risk relapsed ALL, based on MRD in the bone marrow after induction, from the Japanese Pediatric Leukemia/Lymphoma Study Group (JPLSG) ALL-R08-II nationwide cohort (UMIN000002025). RESULTS: Twenty patients with post-induction MRD ≥ 10-3 and two not evaluated for MRD underwent allo-HSCT. Engraftment was confirmed in all patients, and no transplantation-related mortality was observed. The 3-year event-free survival and overall survival rates after transplantation were 86.4% ± 7.3% and 95.5% ± 4.4%, respectively. CONCLUSION: Allo-HSCT based on post-induction MRD with TBI + ETP + CY conditioning was feasible in Japanese children with intermediate-risk relapsed ALL.
Assuntos
Transplante de Células-Tronco Hematopoéticas , Leucemia-Linfoma Linfoblástico de Células Precursoras , Humanos , Criança , Etoposídeo , Irradiação Corporal Total , Condicionamento Pré-Transplante/efeitos adversos , Ciclofosfamida , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Recidiva , Estudos RetrospectivosRESUMO
Three children treated with bone marrow transplantation for acute lymphoblastic leukemia, Diamond-Blackfan anemia, and congenital amegakaryocytic thrombocytopenia developed secondary osteosarcoma in the left tibia at the age of 13, 13, and 9 years, respectively, at 51, 117, and 106 months after transplantation, respectively. Through treatment with chemotherapy and surgery, all 3 patients are alive without disease. We surveyed the literature and reviewed 10 cases of osteosarcoma after hematopoietic stem cell transplantation (SCT), including our 3 cases. Eight of the patients had received myeloablative total body irradiation before SCT. The mean interval from SCT to the onset of osteosarcoma was 6 years and 4 months, and the mean age at the onset of osteosarcoma was 14 years and 5 months. The primary site of the post-SCT osteosarcoma was the tibia in 6 of 10 cases, in contrast to de novo osteosarcoma, in which the most common site is the femur. At least 7 of the 10 patients are alive without disease. Osteosarcoma should be one of the items for surveillance in the follow-up of patients who undergo SCT.
Assuntos
Transplante de Medula Óssea/efeitos adversos , Neoplasias Ósseas/etiologia , Osteossarcoma/etiologia , Adolescente , Criança , Humanos , MasculinoRESUMO
Gabapentinoids are specific ligands for the α2δ-1 subunit of voltage-gated calcium channels. This class of drugs, including gabapentin and pregabalin, exert various pharmacological effects and are widely used for the treatment of epilepsy, anxiety, and chronic pain. The mechanism of action of gabapentinoids involves both direct modulation of calcium channel kinetics and inhibition of channel trafficking and expression, which contribute to the above pharmacological effects. In the present study, we investigated the effects of mirogabalin, a novel potent gabapentinoid, on expression levels of the α2δ-1 subunit in the spinal dorsal horn in a rat model of spinal nerve ligation (SNL) as an experimental animal model for peripheral neuropathic pain. The neuropathic pain state was induced by SNL in male Sprague - Dawley rats. After the development of mechanical hypersensitivity, the animals received 10 mg/kg mirogabalin or vehicle orally for 5 consecutive days and were subjected to immunohistochemical analysis of α2δ-1 subunit expression in the spinal cord. In the SNL model rats, expression of the α2δ-1 subunit significantly increased in the spinal dorsal horn at the ipsilateral side of nerve injury, while mirogabalin inhibited this increase. In conclusion, the α2δ-1 subunit was upregulated in the spinal dorsal horn of SNL model rats, and repeated administration of mirogabalin inhibited this upregulation. The inhibitory effect of mirogabalin on upregulation of the α2δ-1 subunit after nerve injury is considered to contribute to its analgesic effects in peripheral neuropathic pain.
Assuntos
Canais de Cálcio Tipo L , Neuralgia , Ratos , Masculino , Animais , Regulação para Cima , Canais de Cálcio Tipo L/metabolismo , Canais de Cálcio Tipo L/uso terapêutico , Ratos Sprague-Dawley , Neuralgia/tratamento farmacológico , Neuralgia/metabolismo , Nervos Espinhais/metabolismo , Corno Dorsal da Medula Espinal/metabolismoRESUMO
Of 197 cases of canine oral malignant melanoma, 29 cases with myxoid, cartilage, and osteoid formation were studied pathologically and immunohistochemically. Tumor tissues were classified into spindle cell type (13 cases), epithelioid cell type (1 case), and mixed type (15 cases). Myxoid matrixes (29 tumors) were formed mainly in the tissues of spindle cell type and were positive for Alcian blue (pH 2.5). Cartilaginous matrixes (12 tumors) were formed in the myxoid tumor tissues. The morphology of atrophied neoplastic cells, which were embedded in the cartilage cavities, significantly differed from that of spindle cells proliferating in surroundings. There were reticular areas in the process of transitioning from myxoid to cartilaginous matrixes. Osteoid matrixes were not continuous with myxoid or cartilaginous matrixes, and arose as eosinophilic trabeculae in the dense collagenous connective tissues. A calcified bone trabecula was present among the osteoid trabeculae in a case. Melanin-producing melanocytes were proliferating in the collagenous matrixes, while amelanotic cells were in the osteoid matrixes. Immunohistochemistry demonstrated proliferating neoplastic cells as melanocytes. All cells in/out of these three matrixes were positive for Melan-A, S-100 protein, NSE, and vimentin. From these results, it is suggested that cartilage and osteoid matrixes are produced by dedifferentiated melanocytes.
Assuntos
Osso e Ossos/patologia , Cartilagem/patologia , Doenças do Cão/patologia , Melanoma/veterinária , Neoplasias Bucais/veterinária , Ossificação Heterotópica/veterinária , Animais , Cães , Feminino , Imuno-Histoquímica , Masculino , Melanoma/patologia , Neoplasias Bucais/patologia , Ossificação Heterotópica/patologia , Estudos RetrospectivosRESUMO
Reversible cerebral vasoconstriction syndrome (RCVS) is a syndrome characterized by severe headache with segmental vasoconstriction of the cerebral arteries that resolves within 12 weeks. A 16-year-old girl with refractory cytopenia of childhood, who was receiving the immunosuppressant cyclosporine, developed severe headache and was diagnosed with RCVS using magnetic resonance imaging, including magnetic resonance angiography (MRA). MRA is a non-invasive and very effective technique for diagnosing RCVS. MRA should be performed at the onset of severe headache during immunosuppressant administration for children with hematological disorders and may prevent sequelae such as posterior reversible encephalopathy syndrome or ischemic attack.
RESUMO
To evaluate the possibility that Streptococcus equi subsp. zooepidemicus (S.z) the causative bacterial agent of equine shipping fever pneumonia (ESFP), as well as to investigate its pathogenesis, 10 horses (seven Thoroughbreds and three Anglo-Arab species, ranging from 2-4 years in age) were experimentally inoculated, via an endoscope, into bronchus of the lung lobe with a dose of 30 ml of 1-7 x 10(8) CFU/ml of S.z. After inoculation, autopsy and pathological examinations were sequentially conducted 30 min, 1, 2, 3, 4, 17, 20 hr and 2 weeks later. Pneumonia induced by the intrapulmonary inoculation of S.z was characterized by small purulent pneumonic foci in the inoculated areas. With the lapse of time, these foci developed into serous hemorrhagic pneumonia, hemorrhagic purulent pneumonia, and then purulent, coagulation necrotic pneumonia. These pathomorphological characteristics of experimental pneumonia closely resemble those naturally occurring ESFP. There is strong evidence that S.z. is implicated as a causal factor in ESFP. S.z. grew in the mucus, exudate, and pulmonary effusions. Further, the bacteria showed resistance against phagocytosis by pulmonary alveolar macrophages (PAM) and neutrophils. Inhibition of PAM and neutrophil function is considered to be important in the development of pneumonia. With the progression of the disease, the neutrophils often adhered to the endothelial surface of the alveolar capillary lumen and played a role in generating coagulation necrosis of lung tissues.
Assuntos
Doenças dos Cavalos/microbiologia , Doenças dos Cavalos/patologia , Pneumonia Bacteriana/microbiologia , Pneumonia Bacteriana/veterinária , Streptococcus equi/fisiologia , Animais , Feminino , Cavalos/microbiologia , Pulmão/microbiologia , Pulmão/patologia , Masculino , Pneumonia Bacteriana/patologiaAssuntos
Antineoplásicos/uso terapêutico , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Inibidores de Proteínas Quinases/uso terapêutico , Pirimidinas/uso terapêutico , Transplante de Medula Óssea , Criança , Dasatinibe/farmacologia , Dasatinibe/uso terapêutico , Resistencia a Medicamentos Antineoplásicos , Humanos , Mesilato de Imatinib/farmacologia , Mesilato de Imatinib/uso terapêutico , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Indução de Remissão , Resultado do TratamentoRESUMO
A mouse model study using mouse brain-adapted influenza A virus was performed to establish the prophylaxis and treatment of influenza encephalitis and encephalopathy. All mice died after intranasal inoculation of the brain-adapted influenza A virus (H7N3), and the pathological findings indicated the presence of significant encephalitis. Viral antigen was also detected in the brain, both pathologically and virologically. By contrast, infected mice immunized with inactivated vaccine of the same strain did not lose weight, which is an indicator of the overall condition of the mice, and all of them survived. Similarly, antiserum treatment in the early period (0-1 day post-infection) resulted in 100% survival, and no pathological findings were observed in the brain. However, mice treated with antiserum 3 days post-infection showed encephalitis with viral antigens in both glial cells and neurocytes. Although amantadine treatment for 4 days delayed weight loss, it did not prevent death from encephalitis. These results show vaccination and early antiserum treatment to be highly effective, whereas 4-day treatment of amantadine was not very effective in treating or preventing influenza encephalitis. The life-prolonging effect of amantadine, however, suggests that use of amantadine together with other treatments may inhibit the progression of encephalitis.