RESUMO
Stenotrophomonas maltophilia (S. maltophilia) is an aerobic nonfermenting Gram-negative bacillus widely distributed in the environment that has inherent multidrug resistance to beta-lactam and carbapenem antibiotics. S. maltophilia infection (SMI) is known as an important fatal complication following allogeneic hematopoietic stem cell transplantation (HSCT), but its clinical characteristics have not been well clarified. A retrospective study to identify the incidence, risk factors, and outcomes of SMI after allogeneic HSCT was performed using the database of the Japanese nationwide registry, including 29,052 patients who received allogeneic HSCT in Japan between January 2007 and December 2016. A total of 665 patients developed SMI (sepsis/septic shock, 432; pneumonia, 171; other, 62). The cumulative incidence of SMI at 100 days after HSCT was 2.2%. Among risk factors identified for SMI (age ≥ 50 years, male, performance status 2-4, cord blood transplantation [CBT], myeloablative conditioning, Hematopoietic Cell Transplant-Comorbidity Index [HCT-CI] score 1-2, HCT-CI score ≥ 3, and active infectious disease at HSCT), CBT was the strongest risk factor (hazard ratio, 2.89; 95%CI, 1.94-4.32; p < 0.001). The survival rate at day 30 after SMI was 45.7%, and SMI before neutrophil engraftment was significantly associated with poor survival (survival rate 30 days after SMI, 40.1% and 53.8% in patients with SMI before and after engraftment, respectively; p = 0.002). SMI is rare after allogeneic HSCT, but its prognosis is extremely poor. CBT was a strong risk factor for SMI, and its development prior to neutrophil engraftment was associated with poor survival.
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Infecções por Bactérias Gram-Negativas , Transplante de Células-Tronco Hematopoéticas , Stenotrophomonas maltophilia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Infecções por Bactérias Gram-Negativas/epidemiologia , Infecções por Bactérias Gram-Negativas/etiologia , Bactérias Gram-Negativas , Fatores de RiscoRESUMO
Pneumococcal diseases are one of the most important infectious complications in the late period following allogeneic hematopoietic stem cell transplantation (allo-HSCT). The importance of long-term follow-up care is increasing, as the number of long-term survivors following allo-HSCT increases, but there has been a dearth of research specifically focusing on pneumococcal diseases during the late post-transplant period (day >100). Using a transplant registry database between January 1, 2001 and December 31, 2011, we aimed to assess the clinical spectrum and risk factors for pneumococcal diseases in the late post-transplant period. Among the 22,514 recipients who received allo-HSCT over an 11-year period and could be followed for ≥100 days, 43 patients developed 49 episodes of pneumococcal diseases. Six of the 43 patients died from pneumococcal diseases, and four of these six patients died within a week, despite having undergone allo-HSCT two or more years ago. A history of chronic graft-versus-host disease (odds ratio [OR], 2.31; 95% confidence interval [CI], 1.15-4.66; P = 0.02), viral infection (OR, 3.38; 95% CI, 1.70-6.72; P < 0.01), and complete remission of the underlying disease at the time of transplantation (OR, 2.38; 95%CI, 1.10-5.14; P = 0.03) were identified as risk factors. Given the risk of sudden death and the high mortality rate, attention should be paid to pneumococcal diseases in providing long-term follow-up care, even several years after allo-HSCT.
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Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Infecções Pneumocócicas , Humanos , Transplante Homólogo/efeitos adversos , Estudos Retrospectivos , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Infecções Pneumocócicas/epidemiologia , Infecções Pneumocócicas/complicações , Fatores de Risco , Doença Enxerto-Hospedeiro/epidemiologia , Doença Enxerto-Hospedeiro/etiologiaRESUMO
Chemotherapy in combination with mogamulizumab (Mog) was approved in Japan in 2014 for untreated aggressive adult T-cell leukaemia-lymphoma (ATL), but the survival benefit remains unclear. Therefore, we retrospectively analysed clinical outcomes in 39 transplant-ineligible patients with untreated aggressive ATL at Kumamoto University Hospital between 2010 and 2021. The probability of four-year overall survival was 46.3% in the first-line Mog-containing treatment group compared to 20.6% in the chemotherapy-alone group (p = 0.033). Furthermore, this survival benefit was observed even in the elderly. In conclusion, first-line Mog-containing treatment can be a promising strategy for transplant-ineligible patients with ATL, especially in the elderly.
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Leucemia-Linfoma de Células T do Adulto , Adulto , Idoso , Anticorpos Monoclonais Humanizados/uso terapêutico , Humanos , Japão , Leucemia-Linfoma de Células T do Adulto/patologia , Estudos RetrospectivosRESUMO
OBJECTIVES: CCAAT/enhancer-binding protein α (CEBPA) is an essential transcription factor for myeloid differentiation. Not only mutation of the CEBPA gene, but also promoter methylation, which results in silencing of CEBPA, contributes to the pathogenesis of acute myeloid leukemia (AML). We sought for another differentially methylated region (DMR) that associates with the CEBPA silencing and disease phenotype. METHODS: Using databases, we identified a conserved DMR in the CEBPA 3'-untranslated region (UTR). RESULTS: Methylation-specific PCR analysis of 231 AML cases showed that hypermethylation of the 3'-UTR was associated with AML that had a myeloid/NK/T-cell phenotype and downregulated CEBPA. Most of these cases were of an immature phenotype with CD7/CD56 positivity. These cases were significantly associated with lower hemoglobin levels than the others. Furthermore, we discovered that the CEBPA 3'-UTR DMR can enhance transcription from the CEBPA native promoter. In vitro experiments identified IKZF1-binding sites in the 3'-UTR that are responsible for this increased transcription of CEBPA. CONCLUSIONS: These results indicate that the CEBPA 3'-UTR DMR is a novel regulatory element of CEBPA related to myeloid/NK/T-cell lineage leukemogenesis. Transcriptional regulation of CEBPA by IKZF1 may provide a clue for understanding the fate determination of myeloid vs. NK/T-lymphoid progenitors.
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Regiões 3' não Traduzidas , Proteínas Estimuladoras de Ligação a CCAAT/genética , Predisposição Genética para Doença , Leucemia Aguda Bifenotípica/diagnóstico , Leucemia Aguda Bifenotípica/genética , Sequências Reguladoras de Ácido Nucleico , Sítios de Ligação , Biomarcadores , Metilação de DNA , Epigênese Genética , Estudos de Associação Genética , Humanos , Imunofenotipagem , Leucemia Aguda Bifenotípica/metabolismo , Células Mieloides/metabolismo , Células Mieloides/patologia , Células T Matadoras Naturais/metabolismo , Células T Matadoras Naturais/patologia , Fenótipo , Ligação ProteicaRESUMO
To characterize the incidences and outcomes of late acute (LA) and chronic graft-versus-host disease (GVHD) in East Asians according to the 2014 National Institutes of Health criteria, we retrospectively analyzed 506 consecutive Japanese patients who had a first allogeneic hematopoietic cell transplantation (HCT) at our center between 2006 and 2013. According to manifestations at onset 91 patients (60%) had LA GVHD and 60 (40%) had chronic GVHD. The cumulative incidences of LA and chronic GVHD were 20% and 17%, respectively, at 48 months after HCT. The involved sites at the onset of LA GVHD included the skin (71%), gut (13%), and liver (8%). The cumulative incidences of relapse, nonrelapse mortality (NRM), transition to chronic GVHD, and discontinued systemic treatment were 11%, 6%, 22%, and 46%, respectively, at 48 months after onset of LA GVHD. Cox models showed that prior acute GVHD was associated with NRM, and HCT from a female donor to a male patient, myeloablative conditioning, and low Karnofsky performance status were associated with a longer duration of systemic treatment after LA GVHD. The most frequently involved sites at the onset of chronic GVHD included the mouth (83%), liver (75%), skin (69%), and eyes (62%). Cox models showed that use of antithymocyte globulin in conditioning regimens was associated with a higher risk of discontinued systemic treatment after the onset of chronic GVHD. The cumulative incidences of relapse, NRM, and discontinued systemic treatment were 16%, 11%, and 41%, respectively, at 48 months after the onset of chronic GVHD. Our results suggested several potential differences between Japanese patients and those of other ethnicities. A direct comparison is needed to formally investigate ethnic differences.
Assuntos
Consenso , Doença Enxerto-Hospedeiro/mortalidade , Transplante de Células-Tronco Hematopoéticas , Modelos Biológicos , Doença Aguda , Adolescente , Adulto , Idoso , Aloenxertos , Povo Asiático , Doença Crônica , Intervalo Livre de Doença , Feminino , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/prevenção & controle , Humanos , Incidência , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Fatores Sexuais , Taxa de Sobrevida , Fatores de TempoRESUMO
BACKGROUND: Bleeding from hemorrhagic shock can be immediately controlled by blocking the proximal part of the hemorrhagic point using either resuscitative thoracotomy for aortic cross-clamping or insertion of a large-caliber (10-14Fr) resuscitative endovascular balloon occlusion of the aorta (REBOA) device via the femoral artery. However, such methods are very invasive and have various complications. With recent progress in endovascular treatment, a low-profile REBOA device (7Fr) has been developed. OBJECTIVE: The objective of this study was to report our experience of this low-profile REBOA device and to evaluate the usefulness of emergency physician-operated REBOA in life-threatening hemorrhagic shock. METHODS: Ten patients with refractory hemorrhagic shock underwent REBOA using this device via the femoral artery. All REBOA procedures were performed by emergency physicians. The success rate of the insertion, vital signs, and REBOA-related complications were evaluated. RESULTS: Median age was 54 years (interquartile range 33-78 years). The causes of hemorrhagic shock were trauma (n = 4; 1 blunt and 3 penetrating), ruptured abdominal aortic aneurysm (n = 3), and obstetric hemorrhage (n = 3). Two patients had cardiopulmonary arrest upon arrival. REBOA procedure was successful in all patients, and all became hemodynamically stable to undergo definitive interventions after REBOA. There were no REBOA-related complications. The mortality rate within 24 h and 30 days was 40%. CONCLUSIONS: This REBOA device was useful for emergency physicians in life-threatening hemorrhagic shock because of its ease in handling and low invasiveness.
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Aorta/lesões , Oclusão com Balão/normas , Hemorragia/terapia , Adulto , Idoso , Aorta/fisiopatologia , Oclusão com Balão/métodos , Procedimentos Endovasculares/instrumentação , Procedimentos Endovasculares/métodos , Feminino , Humanos , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Ressuscitação/métodos , Estudos Retrospectivos , Choque Hemorrágico/epidemiologia , Choque Hemorrágico/prevenção & controle , Choque Hemorrágico/cirurgiaRESUMO
Adult T-cell leukemia-lymphoma is a distinct type of peripheral T-cell lymphoma caused by human T-cell lymphotropic virus type I. Although allogeneic stem cell transplantation after chemotherapy is a recommended treatment option for patients with aggressive adult T-cell leukemia-lymphoma, there is no consensus about indications for allogeneic stem cell transplantation because there is no established risk stratification system for transplant eligible patients. We conducted a nationwide survey of patients with aggressive adult T-cell leukemia-lymphoma in order to construct a new, large database that includes 1,792 patients aged 70 years or younger with aggressive adult T-cell leukemia-lymphoma who were diagnosed between 2000 and 2013 and received intensive first-line chemotherapy. We randomly divided patients into two groups (training and validation sets). Acute type, poor performance status, high soluble interleukin-2 receptor levels (> 5,000 U/mL), high adjusted calcium levels (≥ 12 mg/dL), and high C-reactive protein levels (≥ 2.5 mg/dL) were independent adverse prognostic factors used in the training set. We used these five variables to divide patients into three risk groups. In the validation set, median overall survival for the low-, intermediate-, and high-risk groups was 626 days, 322 days, and 197 days, respectively. In the intermediate- and high-risk groups, transplanted recipients had significantly better overall survival than non-transplanted patients. We developed a promising new risk stratification system to identify patients aged 70 years or younger with aggressive adult T-cell leukemia-lymphoma who may benefit from upfront allogeneic stem cell transplantation. Prospective studies are warranted to confirm the benefit of this treatment strategy.
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Leucemia-Linfoma de Células T do Adulto/diagnóstico , Adulto , Fatores Etários , Idoso , Biomarcadores , Bases de Dados Factuais , Gerenciamento Clínico , Progressão da Doença , Feminino , Pesquisas sobre Atenção à Saúde , Transplante de Células-Tronco Hematopoéticas , Humanos , Japão , Leucemia-Linfoma de Células T do Adulto/mortalidade , Leucemia-Linfoma de Células T do Adulto/terapia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Análise de Sobrevida , Transplante Homólogo , Adulto JovemRESUMO
OBJECTIVES: Innate immune dysfunction after major burn injuries increases the susceptibility to organ failure. Lipid mediators of inflammation resolution, e.g., resolvin D2, have been shown recently to restore neutrophil functionality and reduce mortality rate in a rat model of major burn injury. However, the physiological mechanisms responsible for the benefic activity of resolvin D2 are not well understood. DESIGN: Prospective randomized animal investigation. SETTING: Academic research setting. SUBJECTS: Wistar male rats. INTERVENTIONS: Animals were subjected to a full-thickness burn of 30% total body surface area. Two hours after burn, 25 ng/kg resolvin D2 was administered IV and repeated every day, for 8 days. At day 10 post burn, 2 mg/kg of lipopolysaccharide was administered IV, and the presence of renal and hepatic injuries was evaluated at day 11 post burn by histology, immunohistochemistry, and relevant blood chemistry. MEASUREMENTS AND MAIN RESULTS: In untreated animals, we found significant tissue damage in the kidneys and liver, consistent with acute tubular necrosis and multifocal necrosis, and changes in blood chemistry, reflecting the deterioration of renal and hepatic functions. We detected less tissue damage and significantly lower values of blood urea nitrogen (26.4 ± 2.1 vs 36.0 ± 9.3 mg/dL; p ≤ 0.001), alanine aminotransferase (266.5 ± 295.2 vs 861.8 ± 813.7 U/L; p ≤ 0.01), and total bilirubin (0.13 ± 0.05 vs 0.30 ± 0.14 mg/dL; p ≤ 0.01) in resolvin D2-treated rats than in untreated animals. The mean blood pressure of all animals was above 65 mm Hg, indicating adequate tissue perfusion throughout the experiments. We measured significantly larger amounts of chromatin in the circulation of untreated than of resolvin D2-treated rats (575.1 ± 331.0 vs 264.1 ± 122.4 ng/mL; p ≤ 0.05) and identified neutrophil extracellular traps in kidney and liver tissues from untreated rats, consistent with the tissue damage. CONCLUSIONS: Pathologic changes in kidney and liver tissues in a rat model of major burn and endotoxin insults are ameliorated by resolvin D2.
Assuntos
Queimaduras/complicações , Ácidos Docosa-Hexaenoicos/farmacologia , Insuficiência Hepática/tratamento farmacológico , Insuficiência Hepática/etiologia , Insuficiência Renal/tratamento farmacológico , Insuficiência Renal/etiologia , Animais , Análise Química do Sangue , Peso Corporal , Modelos Animais de Doenças , Hemodinâmica , Insuficiência Hepática/patologia , Inflamação/metabolismo , Mediadores da Inflamação/metabolismo , Testes de Função Renal , Lipopolissacarídeos/farmacologia , Testes de Função Hepática , Proteína-2 Relacionada a Receptor de Lipoproteína de Baixa Densidade/biossíntese , Masculino , Estudos Prospectivos , Distribuição Aleatória , Ratos , Ratos Wistar , Insuficiência Renal/patologiaRESUMO
To evaluate the impact of graft-versus-host disease (GVHD) and prognostic factors for patients with myelodysplastic syndrome (MDS) after allogeneic hematopoietic cell transplantation (allo-HCT), we retrospectively reviewed 115 patients with MDS or acute myeloid leukemia with multilineage dysplasia (AML-MLD) after allo-HCT at our center. Eighty one patients received reduced-intensity conditioning (RIC) regimens, whereas 34 received myeloablative conditioning regimens. Although the RIC group was significantly older and included more patients with poor cytogenetic risk, no difference in 4-yr overall survival (OS) was seen between the two groups. In a multivariate analysis, covariates associated with a worse OS were the French-American-British stage of refractory anemia excess blasts in transformation/AML-MLD at peak, poor cytogenetic risk, bone marrow blasts of 20% or higher at HCT and the absence of chronic GVHD (cGVHD). By using semi-landmark analyses, we found that the presence of cGVHD significantly improved OS in high-risk patients or the RIC group. However, there was no difference in OS between those with and without cGVHD among low-risk MDS patients. These findings suggest that the graft-versus-leukemia effect may be more beneficial in high-risk patients who do not receive intensive preparative regimens.
Assuntos
Doença Enxerto-Hospedeiro/etiologia , Transplante de Células-Tronco Hematopoéticas , Síndromes Mielodisplásicas/complicações , Síndromes Mielodisplásicas/terapia , Adulto , Idoso , Causas de Morte , Feminino , Seguimentos , Doença Enxerto-Hospedeiro/tratamento farmacológico , Doença Enxerto-Hospedeiro/prevenção & controle , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/mortalidade , Pré-Medicação , Recidiva , Condicionamento Pré-Transplante , Transplante Homólogo , Resultado do Tratamento , Adulto JovemRESUMO
Drug development is a lengthy process with a high failure rate. Increasingly, machine learning is utilized to facilitate the drug development processes. These models aim to enhance our understanding of drug characteristics, including their activity in biological contexts. However, a major challenge in drug response (DR) prediction is model interpretability as it aids in the validation of findings. This is important in biomedicine, where models need to be understandable in comparison with established knowledge of drug interactions with proteins. drGAT, a graph deep learning model, leverages a heterogeneous graph composed of relationships between proteins, cell lines, and drugs. drGAT is designed with two objectives: DR prediction as a binary sensitivity prediction and elucidation of drug mechanism from attention coefficients. drGAT has demonstrated superior performance over existing models, achieving 78% accuracy (and precision), and 76% F1 score for 269 DNA-damaging compounds of the NCI60 drug response dataset. To assess the model's interpretability, we conducted a review of drug-gene co-occurrences in Pubmed abstracts in comparison to the top 5 genes with the highest attention coefficients for each drug. We also examined whether known relationships were retained in the model by inspecting the neighborhoods of topoisomerase-related drugs. For example, our model retained TOP1 as a highly weighted predictive feature for irinotecan and topotecan, in addition to other genes that could potentially be regulators of the drugs. Our method can be used to accurately predict sensitivity to drugs and may be useful in the identification of biomarkers relating to the treatment of cancer patients.
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Primary graft failure (PGF) and multi-lineage cytopenia (MLC) increase the risk of nonrelapse mortality in allogeneic hematopoietic cell transplants (HCT). We evaluated the impact of post-transplant cyclophosphamide (PTCy) and splenomegaly on PGF and MLC for hematological malignancies. This study included patients with PTCy (N=84) and conventional graft-vs.-host disease prophylaxis (N=199). The occurrence of splenomegaly varied widely, ranging from 17.1â¯% (acute myeloid leukemia) to 66.7â¯% (myeloproliferative neoplasms). Ten patients (N=8 in the PTCy and N=2 in the non- PTCy) developed PGF, and 44 patients developed MLC (both N=22). PTCy and severe splenomegaly (≥20â¯cm) were risk factors for PGF (odds ratio (OR): 10.40, p<0.01 and 6.74, p=0.01 respectively). Moreover, severe splenomegaly was a risk factor for PGF in PTCy patients (OR: 10.20, p=0.01). PTCy (hazard ratio (HR) 2.09, p=0.02), moderate (≥15, <20â¯cm, HR 4.36, p<0.01), and severe splenomegaly (HR 3.04, p=0.01) were independent risk factors for MLC. However, in subgroup analysis in PTCy patients, only mild splenomegaly (≥12, <15â¯cm, HR 4.62, p=0.01) was a risk factor for MLC. We recommend all patients be screened for splenomegaly before HCT, and PTCy is cautioned in those with splenomegaly.
Assuntos
Ciclofosfamida , Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Esplenomegalia , Humanos , Ciclofosfamida/efeitos adversos , Ciclofosfamida/uso terapêutico , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Esplenomegalia/etiologia , Feminino , Masculino , Pessoa de Meia-Idade , Adulto , Doença Enxerto-Hospedeiro/etiologia , Adolescente , Adulto Jovem , Idoso , Rejeição de Enxerto/etiologia , Transplante Homólogo/efeitos adversos , Fatores de Risco , Estudos Retrospectivos , Imunossupressores/efeitos adversos , Imunossupressores/uso terapêutico , Neoplasias Hematológicas/terapia , Criança , CitopeniaAssuntos
Anticorpos Monoclonais/uso terapêutico , Transplante de Células-Tronco Hematopoéticas , Leucemia-Linfoma de Células T do Adulto/mortalidade , Leucemia-Linfoma de Células T do Adulto/terapia , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/terapia , Receptores CCR4/antagonistas & inibidores , Adulto , Idoso , Terapia Combinada , Feminino , Seguimentos , Humanos , Leucemia-Linfoma de Células T do Adulto/patologia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Transplante HomólogoRESUMO
This study introduces a novel machine learning methodology for predicting GlutoPeak test parameters from image data, leveraging AutoKeras and transfer learning. The GlutoPeak test is a tool used in the baking industry to evaluate the properties of flour, based on its gluten strength and elasticity. Our research aimed to devise an efficient and cost-effective technique for quantifying the gluten properties of wheat varieties. We aimed to accomplish this by predicting the GlutoPeak test results with convolutional neural network (CNN) models, utilizing the benefits of transfer learning and AutoKeras. AutoKeras is a public code repository capable of automating neural architecture search and hyperparameter tuning. The ResNet101 model, when trained with the Adam optimizer, achieved the highest accuracy of 0.5765 in the 2-class prediction. Meanwhile, the ResNet101 model trained with the SGD optimizer reached the highest accuracy of 0.4362 in the 4-class prediction. The outcomes of this study illustrate the possibility in using machine learning and deep learning techniques for predicting GlutoPeak test parameters from image data. This offers a faster and more cost-effective approach for evaluating gluten quality in wheat varieties.
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This Japanese nationwide retrospective study investigated the impact of HLA-mismatched unrelated transplantation for adult T-cell leukemia-lymphoma (ATL) patients who received transplantation between 2000 and 2018. We compared 6/6 antigen-matched related donor (MRD), 8/8 allele-matched unrelated donor (8/8MUD), and 1 allele-mismatched unrelated donor (7/8MMUD) in the graft-versus-host direction. We included 1191 patients; 449 (37.7%) were in the MRD group, 466 (39.1%) in the 8/8MUD group, and 276 (23.7%) in the 7/8MMUD group. In the 7/8MMUD group, 97.5% of patients received bone marrow transplantation, and no patients received post-transplant cyclophosphamide. The cumulative incidences of non-relapse mortality (NRM) and relapse at 4 years, and the probabilities of overall survival at 4 years in the MRD group were 24.7%, 44.4%, 37.5%, in the 8/8MUD group were 27.2%, 38.2%, and 37.9%, and in the 7/8MMUD group were 34.0%, 34.4%, and 35.3%, respectively. The 7/8MMUD group had a higher risk of NRM (hazard ratio (HR) 1.50 [95% CI, 1.13-1.98; P = 0.005]) and a lower risk of relapse (HR 0.68 [95% CI, 0.53-0.87; P = 0.003]) than the MRD group. The donor type was not a significant risk factor for overall mortality. These data suggest that 7/8MMUD is an acceptable alternative donor when an HLA-matched donor is unavailable.
Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Leucemia-Linfoma de Células T do Adulto , Linfoma , Adulto , Humanos , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Leucemia-Linfoma de Células T do Adulto/terapia , Leucemia-Linfoma de Células T do Adulto/complicações , Transplante Homólogo/efeitos adversos , Estudos Retrospectivos , Doadores não Relacionados , Recidiva , Linfoma/complicações , Doença Enxerto-Hospedeiro/etiologiaRESUMO
BACKGROUND: Traumatic tension gastrothorax is a rare and potentially fatal condition occurring in patients with congenital or acquired diaphragmatic defects. Traumatic tension gastrothorax leads to acute and severe respiratory distress. Delayed tension gastrothorax that develops late during injury can be more severe. CASE PRESENTATION: An 84-year-old woman was brought to our facility with cardiac arrest and returned to spontaneous circulation after 2 min of cardiopulmonary resuscitation. Computed tomography showed diaphragmatic injury and tension gastrothorax due to trauma because of a fall episode few days earlier. Emergency thoracotomy and laparotomy was performed, because nasogastric tube insertion failed. There was a partially necrotic stomach in the chest cavity. The stomach was retracted from the thoracic cavity into the abdominal cavity and placed in its proper position. There was a 5 cm tear of the diaphragm. The tear was sutured and closed and then the necrotic area of the stomach was resected. Although the surgery relieved the intrathoracic compression, it resulted in re-expansion pulmonary edema immediately after surgery and hypoxemia. The patient was unable to overcome the hypoxemic state and eventually died. CONCLUSIONS: Delayed tension gastrothorax can lead not only to obstructive shock due to intrathoracic compression but also to more severe organ ischemia and re-expansion pulmonary edema due to insufflation.
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There remains an unmet clinical need to identify which patients with diffuse large B-cell lymphoma (DLBCL) would benefit from central nervous system (CNS) prophylaxis, due to the low positive predictive value (PPV; 10%-15%) of the currently available predictive models. To stratify patients at high risk of developing CNS relapse, we retrospectively analyzed 182 patients with DLBCL initially treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP), or a R-CHOP-like regimen. Among them, 17 patients relapsed with CNS involvement, and the 2-year rate of CNS relapse was 7.9%. Upon carrying out multivariate analysis, ≥3 extranodal sites and elevated soluble interleukin-2 receptor (sIL-2R) levels at diagnosis were identified as independent risk factors for CNS relapse. The 2-year and 3.5-year rates of CNS relapse were 57.1% and 78.6%, respectively, in patients with both elevated sIL-2R and ≥3 extranodal sites. Furthermore, combined use of these risk factors of both elevated sIL-2R and ≥3 extranodal sites resulted in a high PPV (71.4%), negative predictive value (93.1%), and overall accuracy (92.3%) for undergoing CNS relapse. In conclusion, we propose a simple and valuable tool to predict patients with DLBCL at very high risk of CNS relapse.
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Mogamulizumab (Mog) is effective against adult T-cell leukemia-lymphoma (ATL), but as we reported previously, Mog increases the incidence of severe acute GVHD when administered before allogeneic hematopoietic cell transplantation (allo-HCT). Here, we report the cases of two ATL patients who did not develop acute GVHD despite receiving Mog before allo-HCT. Case 1: a 63-year-old female who underwent allo-HCT from an HLA-matched donor 2 months after the last dose of Mog. Case 2: a 47-year-old male with ATL that relapsed 3 months after first allo-HCT. He received eight doses of Mog and underwent a second allo-HCT from a haploidentical donor 4 months after the last dose of Mog. Mog blood levels were measured and lymphocytes analyzed by mass cytometry. Mog blood levels measured before starting the conditioning regimens were low. A small proportion of regulatory T cells (Tregs) was detected before and shortly after allo-HCT. When using Mog before allo-HCT, it is important to consider the number of Mog doses and the interval from the last dose of Mog to allo-HCT. Analyzing Mog blood levels and Treg counts before and after allo-HCT should also be useful.
Assuntos
Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/efeitos adversos , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/prevenção & controle , Transplante de Células-Tronco Hematopoéticas/métodos , Leucemia-Linfoma de Células T do Adulto/terapia , Doença Aguda , Anticorpos Monoclonais Humanizados/sangue , Feminino , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Gravidade do Paciente , Linfócitos T Reguladores , Condicionamento Pré-Transplante , Transplante HomólogoRESUMO
Delivering adequate health care in the setting of the ongoing pandemic is challenging. Due to coronavirus disease 2019 (COVID-19), the Tokyo Metropolitan government has been forced to expand their acute health-care capacity corresponding to infectious diseases within a short period. Responding to this situation, health emergency and disaster experts of the Tokyo Disaster Medical Assistance Team took the initiative in creating a brief education course. We established the course for expanding infectious disease care capacity by a dedicated hands-on lecture for health professionals who are unfamiliar with infectious disease care in ordinary circumstances. Our lecture included the typical course of COVID-19, use of personal protective equipment, environmental sterilization, medical-ward zoning, and safe caregiving. Hospitals that received customized lectures reported by means of a questionnaire that the lectures were well suited to their needs. Currently, the health-care system in Tokyo has increased its capacity to meet the demand and has not been affected by COVID-19. Our experience shows that health emergency and disaster experts can assist hospitals in crisis by providing educational materials.
RESUMO
This study aimed to clarify the risk factors and prognosis associated with blood stream infection (BSI) in allogeneic hematopoietic cell transplantation (allo-HCT), and the relationship between BSI and acute graft-versus-host disease (aGVHD). This retrospective analysis included 11,098 patients in the Japanese national transplant registry. A total of 2172 patients developed BSI after allo-HCT, with 2332 identified pathogens. The cumulative incidences of BSI were 15.5% at 30 days and 20.9% at 100 days after allo-HCT. In a multivariate analysis, severe (grade III-IV) aGVHD was associated with a higher risk of BSI (vs. grade 0-I aGVHD: hazard ratio [HR] 3.34 [95% confidence interval (CI), 2.85-3.92; P < 0.001]). In a multivariate analysis, severe aGVHD before BSI was associated with a higher risk of overall mortality after BSI (vs. grade 0-I aGVHD: HR 2.61 [95% CI 2.18-3.11; P < 0.001]). In addition, BSI (vs. no-BSI: HR 1.20 [95% CI, 1.12-1.29; P < 0.001]) and severe aGVHD (vs. grade 0-I aGVHD: HR 1.97 [95% CI, 1.83-2.12; P < 0.001]) were independent risk factors for overall mortality after allo-HCT. In the setting of allo-HCT, severe aGVHD was associated with increases in both BSI incidence and post-BSI overall mortality. Furthermore, BSI was an independent risk factor for overall mortality.