RESUMEN
Haploidentical haematopoietic cell transplantation (haplo-HCT) using post-transplant cyclophosphamide (PTCY) as graft-versus-host disease (GVHD) prophylaxis is the standard of care for various haematological malignancies. The original PTCY dose after haplo-HCT was 100 mg/kg, but no dose-finding studies have been performed to identify the optimal dose. We performed a retrospective analysis to compare standard-dose PTCY (100 mg/kg) with reduced-dose PTCY (80 mg/kg): 969 in the standard-dose group and 538 in the reduced-dose group. As there was a significant difference between the two groups regarding patient and transplant characteristics, we performed propensity score (PS) matching. After PS matching, 425 patients in each group were included. The probabilities of 2-year OS were 55.9% in the standard-dose group and 47.0% in the reduced-dose group (p = 0.36). The cumulative incidences of 2-year non-relapse mortality were 21.3% in the standard-dose group and 20.5% in the reduced-dose group (p = 0.55). There was no significant difference in the incidence of acute (grade II-IV 29.2% [95% CI, 24.9-33.6] vs. 25.3% [95% CI, 21.3-29.6]; grade III-IV 7.3% [95% CI, 5.1-10.0] vs. 6.6% [95% CI, 4.5-9.3]) or chronic GVHD. In conclusion, reduced- and standard-dose PTCY were comparable in terms of major clinical outcomes.
Asunto(s)
Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Humanos , Trasplante Haploidéntico/efectos adversos , Estudios Retrospectivos , Enfermedad Injerto contra Huésped/etiología , Ciclofosfamida/uso terapéutico , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Acondicionamiento Pretrasplante/efectos adversosRESUMEN
Allogeneic hematopoietic cell transplantation (HCT) potentially provides a cure for patients with acute myeloid leukemia (AML) who are unlikely to be cured with chemotherapy alone. Previously, human leukocyte antigen (HLA)-matched related donors were used exclusively, which made the procedure available for a limited proportion of patients. The introduction of high-resolution HLA-typing technology, innovations in immunosuppressive therapy, and improved supportive care measures have significantly changed the situation. Now, patients without a matched related donor have an ample opportunity to receive allogeneic HCT with the use of matched or mismatched unrelated donors, umbilical cord blood grafts, or haploidentical related donors. The outcomes of alternative donor transplantations have improved over the past decades, and the growth of unrelated donor registries as well as the donor diversification have enhanced the chance of finding a suitable donor. With multiple alternative donor choices available for most patients, the donor selection is becoming increasingly important. To discuss the optimal donor choice in case of unavailability of an HLA-matched related donor, this article reviews the existing literature of retrospective and prospective comparisons of different alternative donor transplantations in AML and discusses the current state-of-art modalities in allogeneic HCT using alternative donors.
RESUMEN
A patient undergoing cord blood transplantation for refractory angioimmunoblastic T-cell lymphoma was subsequently managed with long-term immunosuppressants for chronic graft-versus-host disease (GVHD). On day 591 post-transplant, she exhibited disorientation and cognitive dysfunction. Magnetic resonance imaging (MRI) of the brain revealed two hyperintense foci in the white matter, suggestive of progressive multifocal leukoencephalopathy (PML). However, we did not include PML in the differential diagnosis at that time. Unfortunately, she developed progressive cognitive impairment, and repeated brain MRIs showed a progression in lesion size. She was still taking immunosuppressants to control her GVHD, therefore we suspected PML. The diagnosis of PML was confirmed through the detection of a John Cunningham (JC) virus in the cerebrospinal fluid on day 640 post-transplant. This report highlights the critical need to consider PML in differential diagnoses for post-allogeneic transplant patients, especially those who exhibit progressive neurological symptoms while on prolonged immunosuppressant therapy.
Asunto(s)
Trasplante de Células Madre de Sangre del Cordón Umbilical , Enfermedad Injerto contra Huésped , Inmunosupresores , Leucoencefalopatía Multifocal Progresiva , Imagen por Resonancia Magnética , Humanos , Leucoencefalopatía Multifocal Progresiva/etiología , Leucoencefalopatía Multifocal Progresiva/diagnóstico , Leucoencefalopatía Multifocal Progresiva/líquido cefalorraquídeo , Femenino , Trasplante de Células Madre de Sangre del Cordón Umbilical/efectos adversos , Inmunosupresores/uso terapéutico , Inmunosupresores/efectos adversos , Enfermedad Injerto contra Huésped/etiología , Linfoma de Células T/terapia , Virus JC/aislamiento & purificación , Diagnóstico Diferencial , Persona de Mediana Edad , Encéfalo/diagnóstico por imagen , Encéfalo/patologíaRESUMEN
Use of posttransplant cyclophosphamide (PTCy) for the prophylaxis of graft-versus-host disease (GVHD) has revolutionized the field of HLA-haploidentical stem cell transplantation, which was previously considered high-risk and only feasible in specialized centers. The rapid adoption of PTCy is attributed not only to its superior efficacy in suppressing GVHD but also to its affordability and the lack of need for specialized techniques or equipment to administer it. Recently, PTCy has gained attention for its potential effectiveness in GVHD prophylaxis beyond HLA-haploidentical stem cell transplantation. In a phase III trial (BMT CTN 1703 trial) in patients undergoing allogeneic HLA-matched stem cell transplantation with reduced-intensity conditioning, GVHD-free, relapse-free survival at 1 year was significantly better among those who received PTCy-tacrolimus-mycophenolate mofetil than among those who received tacrolimus-methotrexate. In Japan, a phase II clinical trial that investigated PTCy for GVHD prophylaxis following HLA-matched or 1-2 allele mismatched peripheral blood stem cell transplantation confirmed the efficacy and safety of this approach. Effective suppression of GVHD using PTCy is expected to enhance the safety of allogeneic transplantation, potentially improving transplant outcomes and offering hope for better patient care in the field of transplantation.
Asunto(s)
Ciclofosfamida , Enfermedad Injerto contra Huésped , Humanos , Enfermedad Injerto contra Huésped/prevención & control , Ciclofosfamida/administración & dosificación , Ensayos Clínicos como Asunto , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Inmunosupresores/administración & dosificación , Inmunosupresores/uso terapéutico , Trasplante HomólogoRESUMEN
OBJECTIVES: The cryptic fusion oncogene NUP98::NSD1 is known to be associated with FLT3-ITD mutation in acute myeloid leukemia (AML), and an independent poor prognostic factor in pediatric AML. However, there are little data regarding the clinical significance of NUP98::NSD1 in adult cohort. METHODS: We conducted a multicenter retrospective study to investigate the prevalence, clinical characteristics, and prognostic impact of NUP98::NSD1 in adult FLT3-ITD-positive AML patients. RESULTS: In a total of 97 FLT3-ITD-positive AML patients, six cases (6.2%) were found to harbor the NUP98::NSD1 fusion transcript. NUP98::NSD1 positive cases had significantly higher platelet counts and a higher frequency of FAB-M4 morphology than NUP98::NSD1 negative cases. NUP98::NSD1 was found to be mutually exclusive with NPM1 mutation, and was accompanied by the WT1 mutation in three of the six cases. The presence of NUP98::NSD1 fusion at the time of diagnosis predicted poor response to cytarabine-anthracycline-based intensive induction chemotherapy (induction failure rate: 83% vs. 36%, p = .038). Five of the six cases with NUP98::NSD1 underwent allogeneic hematopoietic stem cell transplantation (HSCT). Two of the five cases have successfully maintained remission, with one of them being rescued through a second HSCT. CONCLUSIONS: Detecting NUP98::NSD1 in adult FLT3-ITD-positive AML is crucial to recognizing chemotherapy-resistant group.
Asunto(s)
Leucemia Mieloide Aguda , Niño , Humanos , Adulto , Estudios Retrospectivos , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/terapia , Pronóstico , Mutación , Tirosina Quinasa 3 Similar a fms/genética , N-Metiltransferasa de Histona-Lisina/genéticaRESUMEN
HCT recipients reportedly have a high mortality rate after developing COVID-19. SARS-CoV-2 vaccination is generally useful to prevent COVID-19. However, its safety and efficacy among HCT recipients remain elusive. This large-scale prospective observational study including 543 HCT recipients with 37-months interval from transplant demonstrated high safety profiles of mRNA vaccine: only 0.9% of patients avoided the second dose due to adverse event or GVHD aggravation following the first dose. Regarding the efficacy, serological response with a clinically relevant titer (≥250 BAU/mL) was obtained in 397 (73.1%) patients. We classified the remaining 146 patients as impaired responders and compared the clinical and immunological parameters between two groups. In allogeneic HCT recipients, multivariable analysis revealed the risk factors for impaired serological response as follows: age (≥60, 1 points), HLA-mismatched donor (1 points), use of systemic steroids (1 points), absolute lymphocyte counts (<1000/µL, 1 points), absolute B-cell counts (<100/µL, 1 points), and serum IgG level (<500 mg/dL, 2 points). Notably, the incidence of impaired serological response increased along with the risk scores: patients with 0, 1-3, and 4-7 points were 3.9%, 21.8%, and 74.6%, respectively. In autologous HCT recipients, a shorter interval from transplant to vaccination was the only risk factor for impaired serological response. Our findings indicate that two doses of SARS-CoV-2 vaccine are safe but insufficient for a part of HCT recipients with higher risk scores. To improve this situation, we should consider additional treatment options, including booster vaccination and prophylactic neutralizing antibodies during the SARS-CoV-2 pandemic.
Asunto(s)
COVID-19 , Trasplante de Células Madre Hematopoyéticas , Humanos , Anticuerpos Antivirales , Formación de Anticuerpos , COVID-19/prevención & control , Vacunas contra la COVID-19/administración & dosificación , Vacunas contra la COVID-19/efectos adversos , Pueblos del Este de Asia , Trasplante de Células Madre Hematopoyéticas/efectos adversos , ARN Mensajero , SARS-CoV-2 , Receptores de Trasplantes , Vacunación , JapónRESUMEN
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.
Asunto(s)
Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Infecciones Neumocócicas , Humanos , Trasplante Homólogo/efectos adversos , Estudios Retrospectivos , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Infecciones Neumocócicas/epidemiología , Infecciones Neumocócicas/complicaciones , Factores de Riesgo , Enfermedad Injerto contra Huésped/epidemiología , Enfermedad Injerto contra Huésped/etiologíaRESUMEN
Proper resolution of inflammation is vital for repair and restoration of homeostasis after tissue damage, and its dysregulation underlies various noncommunicable diseases, such as cardiovascular and metabolic diseases. Macrophages play diverse roles throughout initial inflammation, its resolution, and tissue repair. Differential metabolic reprogramming is reportedly required for induction and support of the various macrophage activation states. Here we show that a long noncoding RNA (lncRNA), lncFAO, contributes to inflammation resolution and tissue repair in mice by promoting fatty acid oxidation (FAO) in macrophages. lncFAO is induced late after lipopolysaccharide (LPS) stimulation of cultured macrophages and in Ly6Chi monocyte-derived macrophages in damaged tissue during the resolution and reparative phases. We found that lncFAO directly interacts with the HADHB subunit of mitochondrial trifunctional protein and activates FAO. lncFAO deletion impairs resolution of inflammation related to endotoxic shock and delays resolution of inflammation and tissue repair in a skin wound. These results demonstrate that by tuning mitochondrial metabolism, lncFAO acts as a node of immunometabolic control in macrophages during the resolution and repair phases of inflammation.
Asunto(s)
Ácidos Grasos/metabolismo , Inflamación/inmunología , Macrófagos/inmunología , Subunidad beta de la Proteína Trifuncional Mitocondrial/genética , ARN Largo no Codificante/metabolismo , Animales , Modelos Animales de Enfermedad , Técnicas de Silenciamiento del Gen , Humanos , Lipopolisacáridos/inmunología , Activación de Macrófagos/genética , Macrófagos/metabolismo , Masculino , Ratones , Subunidad beta de la Proteína Trifuncional Mitocondrial/metabolismo , Oxidación-Reducción , Cultivo Primario de Células , ARN Largo no Codificante/genética , Piel/inmunología , Piel/lesiones , Cicatrización de Heridas/inmunologíaRESUMEN
HLA-haploidentical stem cell transplantations using posttransplant cyclophosphamide (PTCy-haplo) rapidly increased worldwide. In Japan, the number of HLA-haploidentical stem cell transplantation cases exceeded related HLA-matched transplants in 2020. Recent retrospective studies using Japanese registry data have reported comparable transplantation outcomes between PTCy-haplo and HLA-matched unrelated and cord blood transplantations. PTCy-haplo was initially developed in the bone marrow transplantation setting after non-myeloablative conditioning but has recently become widely used in peripheral blood stem cell transplantation and myeloablative conditioning. Peripheral blood stem cell transplantation increases the occurrence of graft-versus-host disease but may have more improved transplant outcomes compared with bone marrow transplantation. Other factors, such as the number of infused cluster of differentiation 34-positive cells, donor age, HLA class II mismatch, HLA-B leader, and reduced PTCy dosage, may also contribute to the outcome of PTCy-haplo transplantations. Furthermore, PTCy has been reportedly effective in related/unrelated HLA-matched transplantation and HLA-mismatched unrelated transplantations. A prospective phase II trial using PTCy in patients who underwent HLA-matched and 1-2 allele-mismatched transplantation is ongoing in Japan. Patient enrollment has already been completed, and the results will be revealed soon. Using PTCy to sufficiently reduce the occurrence of graft-versus-host disease will make performing allogeneic transplants with a higher safety level possible.
Asunto(s)
Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Trasplante de Células Madre de Sangre Periférica , Humanos , Estudios Prospectivos , Ciclofosfamida , Enfermedad Injerto contra Huésped/prevención & control , Acondicionamiento Pretrasplante , Estudios RetrospectivosRESUMEN
PURPOSE: Mycophenolate mofetil (MMF), a mycophenolic acid (MPA) prodrug, is used to prevent graft-versus-host disease (GVHD) in hematopoietic stem cell transplantation (HSCT). Although previous studies have reported that enterohepatic circulation (EHC) of MPA, which is usually observed in MMF-treated patients, does not occur in HSCT patients, it is unclear what happens in haploidentical-HSCT (haplo-HSCT) patients, who are using post-transplant cyclophosphamide. This study was conducted to investigate MPA pharmacokinetics in haplo-HSCT patients. METHODS: Seventeen haplo-HSCT patients, who received MMF for GVHD prophylaxis, were enrolled in this study. We collected blood samples on days 14 and 28, and plasma MPA concentrations were measured by high-performance liquid chromatography; pharmacokinetic parameters such as area under the curve (AUC), mean residence time (MRT), and apparent oral clearance (CL/F) were measured with moment analysis. We also evaluated EHC as AUC6-12h/AUC0-12h. RESULTS: There was no significant difference in MPA pharmacokinetic parameters between days 14 and 28. There was also no difference between the pharmacokinetic parameter changes and diarrhea. Additionally, varying plasma MPA concentrations suggested that MPA EHC did not occur. CONCLUSION: In this study, we revealed the pharmacokinetics of MMF in Japanese haplo-HSCT recipients. Additionally, our study demonstrated that MPA EHC might not occur in Japanese haplo-HSCT recipients.
Asunto(s)
Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Área Bajo la Curva , Enfermedad Injerto contra Huésped/prevención & control , Humanos , Inmunosupresores/uso terapéutico , Japón , Ácido Micofenólico/uso terapéuticoRESUMEN
Bing-Neel syndrome (BNS) is a rare disease manifestation of Waldenström's macroglobulinemia characterized by abnormal lymphoplasmacytoid cells infiltration of the central nervous system. In September 2019, a 46-year-old man presented to a previous hospital with hand tremors, nausea, and dysuria. Demyelination of cerebral white matter and the spinal cord was discovered using MRI. Steroid pulse therapy was used to treat inflammatory demyelinating disease, and it provided temporary relief, but the symptoms returned when the steroids were stopped. He was referred to our hospital in June 2020, for further evaluation with the possibility of hematological malignancy. BNS was diagnosed based on the presence of abnormal lymphoplasmacytoid cells in the bone marrow and cerebrospinal fluid (CSF), as well as the presence of the MYD88L265P mutation in the CSF specimen. In July 2020, BR (bendamustine, rituximab) therapy was administered, but it was ineffective. Oral administration of tirabrutinib, which was recently approved for WM, began in August 2020. He has achieved long-term remission and steroid withdrawal, with no notable side effects. This is the second report of successful treatment of BNS with tirabrutinib. More research is needed to confirm tirabrutinib's efficacy in the treatment of BNS.
Asunto(s)
Encefalopatías , Macroglobulinemia de Waldenström , Humanos , Imidazoles/uso terapéutico , Masculino , Persona de Mediana Edad , Pirimidinas/uso terapéutico , Macroglobulinemia de Waldenström/diagnósticoRESUMEN
BACKGROUND: Coronavirus disease 2019 (COVID-19) has rapidly evolved to become a global pandemic, largely owing to the transmission of its causative virus through asymptomatic carriers. Detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in asymptomatic people is an urgent priority for the prevention and containment of disease outbreaks in communities. However, few data are available in asymptomatic persons regarding the accuracy of polymerase chain reaction testing. In addition, although self-collected saliva samples have significant logistical advantages in mass screening, their utility as an alternative specimen in asymptomatic persons is yet to be determined. METHODS: We conducted a mass screening study to compare the utility of nucleic acid amplification, such as reverse-transcription polymerase chain reaction testing, using nasopharyngeal swab (NPS) and saliva samples from each individual in 2 cohorts of asymptomatic persons: the contact-tracing cohort and the airport quarantine cohort. RESULTS: In this mass screening study including 1924 individuals, the sensitivities of nucleic acid amplification testing with NPS and saliva specimens were 86% (90% credible interval, 77%-93%) and 92% (83%-97%), respectively, with specificities >99.9%. The true concordance probability between the NPS and saliva tests was estimated at 0.998 (90% credible interval, .996-.999) given the recent airport prevalence of 0.3%. In individuals testing positive, viral load was highly correlated between NPS and saliva specimens. CONCLUSION: Both NPS and saliva specimens had high sensitivity and specificity. Self-collected saliva specimens are valuable for detecting SARS-CoV-2 in mass screening of asymptomatic persons.
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COVID-19 , SARS-CoV-2 , Humanos , Tamizaje Masivo , Saliva , Manejo de EspecímenesRESUMEN
Antithymocyte globulin (ATG) reduces severe acute and chronic graft-versus-host disease (GVHD) in allogeneic peripheral blood stem cell transplantation (PBSCT). However, risk factors for severe acute GVHD in PBSCT using ATG remain to be determined. We conducted a single-center, retrospective study to analyze the association of acute GVHD requiring systemic corticosteroid (SC-aGVHD) with absolute lymphocyte counts (ALC) before the administration of ATG or conditioning in 53 patients with HLA-matched PBSCT using low-dose thymoglobulin (2 mg/kg) after myeloablative conditioning. The cumulative incidence of SC-aGVHD was 17.0% and ALC before ATG were significantly higher in patients with SC-aGVHD compared to that in patients without it (median, 0.15 × 109/L vs 0.06 × 109/L, P = 0.047). The cumulative incidence of SC-aGVHD was significantly higher in patients with high ALC before ATG (≥ 0.15 × 109/L) than in those with low ALC (38.5% vs 10.0%, P = 0.016). Non-relapse mortality (NRM) was also significantly higher in the high ALC before ATG group than the low ALC before ATG group (2-year NRM: 23.9% vs 6.0%, P = 0.048), leading to worse survival (2-year overall survival: 69.2% vs 83.5%, P = 0.039). Our study suggested that high ALC before ATG is a risk factor for SC-aGVHD.
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Suero Antilinfocítico/uso terapéutico , Enfermedad Injerto contra Huésped/diagnóstico , Inmunosupresores/uso terapéutico , Recuento de Linfocitos , Trasplante de Células Madre de Sangre Periférica , Corticoesteroides/administración & dosificación , Corticoesteroides/efectos adversos , Corticoesteroides/uso terapéutico , Adulto , Anciano , Suero Antilinfocítico/administración & dosificación , Femenino , Enfermedad Injerto contra Huésped/sangre , Enfermedad Injerto contra Huésped/etiología , Humanos , Inmunosupresores/administración & dosificación , Masculino , Persona de Mediana Edad , Trasplante de Células Madre de Sangre Periférica/efectos adversos , Trasplante de Células Madre de Sangre Periférica/métodos , Pronóstico , Estudios Retrospectivos , Acondicionamiento Pretrasplante/efectos adversos , Acondicionamiento Pretrasplante/métodos , Adulto JovenRESUMEN
To overcome the delayed or failed engraftment after unrelated cord blood transplantation (CBT), we conducted a multicenter phase II study of intrabone single-unit CBT without antithymocyte globulin (ATG) for adult patients with hematological malignancies (UMIN-CTR, UMIN000020997). Sixty-four patients received an intrabone injection of unwashed (n = 61) or washed (n = 3) cord blood after local anesthesia. All injection-related adverse events were mild and resolved spontaneously. Sixty-two patients were evaluable for the efficacy of intrabone CBT of serological HLA-A, -B, and -DR ≥ 4/6 matched cord blood with a median number of 2.57 × 107/kg cryopreserved total nucleated cells. The probability of survival with neutrophil engraftment on day 28 was 77.4% (95% confidence interval, 67.0-85.8%), which exceeded the threshold value. The cumulative incidences of neutrophils ≥ 0.5 × 109/L on day 60 was 80.6% (68.2-88.6%), with a median time to recovery of 21 days after transplantation. The cumulative incidences of platelets ≥ 20 × 109/L and platelets ≥ 50 × 109/L on day 100 were 75.8% (62.6-84.9%) and 72.6% (59.4-82.1%), respectively, with median time to platelets ≥ 20 × 109/L and platelets ≥ 50 × 109/L of 38 and 45 days after transplantation, respectively. The cumulative incidences of grade II-IV and III-IV acute graft-versus-host disease were 29.0% and 6.5%, respectively. All responded to steroid therapy, and secondary treatments were not required. The present study suggests the efficacy of intrabone single-unit CBT without ATG in terms of early engraftment and controllable acute graft-versus-host disease.
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Trasplante de Células Madre de Sangre del Cordón Umbilical/métodos , Neoplasias Hematológicas/terapia , Infusiones Intraóseas/métodos , Adolescente , Adulto , Anciano , Suero Antilinfocítico , Huesos , Trasplante de Células Madre de Sangre del Cordón Umbilical/efectos adversos , Femenino , Sangre Fetal/fisiología , Enfermedad Injerto contra Huésped/epidemiología , Enfermedad Injerto contra Huésped/etiología , Enfermedad Injerto contra Huésped/patología , Neoplasias Hematológicas/epidemiología , Humanos , Incidencia , Infusiones Intraóseas/efectos adversos , Japón/epidemiología , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
Rapid and simple point-of-care detection of SARS-CoV-2 is an urgent need to prevent pandemic. Reverse transcription loop-mediated isothermal amplification (RT-LAMP) can detect SARS-CoV-2 more rapidly than RT-PCR. Saliva is non-invasive specimen suitable for mass-screening, but data comparing utility of nasopharyngeal swab (NPS) and saliva in RT-LAMP test are lacking and it remains unclear whether SARS-CoV-2 could be detected by direct processing of samples without the need for prior RNA extraction saliva. In this study, we compared utility of saliva and NPS samples for the detection of SARS-CoV-2 by a novel RT-fluorescence LAMP (RT-fLAMP). The sensitivity and specificity of the RT-fLAMP with RNA extraction were 97% and 100%, respectively, with equivalent utility of NPS and saliva. However, sensitivity was decreased to 71% and 47% in NPS and saliva samples without RNA extraction, respectively, suggesting that RNA extraction process may be critical for the virus detection by RT-fLAMP.
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Prueba de COVID-19/métodos , COVID-19/diagnóstico , Técnicas de Diagnóstico Molecular/métodos , Técnicas de Amplificación de Ácido Nucleico/métodos , ARN Viral/aislamiento & purificación , SARS-CoV-2/aislamiento & purificación , Fluorescencia , Humanos , Tamizaje Masivo/métodos , Nasofaringe/virología , Sistemas de Atención de Punto , ARN Viral/análisis , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa/métodos , Saliva/virología , Sensibilidad y EspecificidadRESUMEN
BACKGROUND: The efficacy and safety of colistin for the treatment of infections caused by multidrug-resistant gram-negative bacilli have been poorly investigated in Japanese patients. This study was performed to investigate the efficacy and safety of colistin in Japanese patients by analyzing a considerable number of cases. Furthermore, we evaluated the relationship between the plasma concentration and efficacy and safety of colistin in some cases. METHODS: A retrospective cohort study was conducted at Hokkaido University Hospital, analyzing patients treated with colistin (colistimethate sodium) during the period from January 2007 to December 2019. RESULTS: Overall, 42 cases were enrolled. Favorable clinical response was observed in 25 cases (59.5%), with an all-cause 30-day mortality of 33.3% (14/42 cases). Microbiological eradication was achieved in 18 cases (42.9%). Nephrotoxicity was observed in 20 cases (47.6%) and was mild and reversible in all cases. Plasma trough concentrations of colistin determined in nine patients correlated with changes in serum creatinine concentration (â¿) and creatinine clearance (%). The cutoff value of colistin trough concentration for nephrotoxicity was 2.02 µg/mL. CONCLUSION: Our results showed approximately 60% clinical efficacy of colistin therapy against infections caused by multidrug-resistant gram-negative bacilli in the patients. Further studies with larger populations are needed to elucidate the efficacy and safety of colistin in Japanese patients.
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Acinetobacter baumannii , Infecciones por Bacterias Gramnegativas , Antibacterianos/efectos adversos , Colistina/efectos adversos , Farmacorresistencia Bacteriana Múltiple , Bacterias Gramnegativas , Infecciones por Bacterias Gramnegativas/tratamiento farmacológico , Humanos , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
INTRODUCTION: The Global Leadership Initiative on Malnutrition (GLIM) lacks reliable blood tests for evaluating the nutrition status. We retrospectively compared the GLIM criteria, Controlling Nutrition Status (CONUT) score, and Subjective Global Assessment (SGA) to establish effective malnutrition screening and provide appropriate nutritional interventions according to severity. METHODS: We classified 177 patients into 3 malnutrition categories (normal/mild, moderate, and severe) according to the GLIM criteria, CONUT score, and SGA. We investigated the malnutrition prevalence, concordance of malnutrition severity, predictability of clinical outcome, concordance by etiology, and clinical outcome by inflammation. RESULTS: The highest prevalence of malnutrition was found using the GLIM criteria (87.6%). Concordance of malnutrition severity was low between the GLIM criteria and CONUT score. Concordance by etiology was low in all groups but was the highest in the "acute disease" group. The area under the curve of clinical outcome and that of the "with inflammation group" were significantly higher when using the CONUT score versus using the other tools (0.679 and 0.683, respectively). CONCLUSION: The GLIM criteria have high sensitivity, while the CONUT score can effectively predict the clinical outcome of malnutrition. Their combined use can efficiently screen for malnutrition and patient severity in acute care hospitals.
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Desnutrición , Estado Nutricional , Hospitales , Humanos , Inflamación , Liderazgo , Desnutrición/diagnóstico , Desnutrición/epidemiología , Evaluación Nutricional , Estudios RetrospectivosRESUMEN
While immune checkpoint inhibitors (ICIs) have antitumor effects, they also have characteristic side effects, including colitis. However, gastritis has rarely been reported. We report a case of a patient with lung adenocarcinoma who presented with epigastric pain and diarrhea following pembrolizumab administration. Sonography of the abdomen demonstrated diffuse, although mild, gastric wall thickening (mainly in the submucosa), as well as a slight decrease in echogenicity throughout the gastric wall. While the mucosal surface was relatively smooth, color Doppler examination showed increased vascularity. Esophagogastroduodenoscopy and pathological examination confirmed the diagnosis of ICI-related gastroenteritis.
Asunto(s)
Gastroenteritis/inducido químicamente , Gastroenteritis/diagnóstico por imagen , Inhibidores de Puntos de Control Inmunológico/efectos adversos , Adenocarcinoma del Pulmón/tratamiento farmacológico , Humanos , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , UltrasonografíaRESUMEN
Graft-versus-host disease (GVHD) is the major complication after allogeneic stem cell transplantation (SCT). Emerging evidence indicates that GVHD leads to injury of intestinal stem cells. However, it remains to be investigated whether skin stem cells could be targeted in skin GVHD. Lgr5+ hair follicle stem cells (HFSCs) contribute to folliculogenesis and have a multipotent capacity to regenerate all epithelial cells in repair. We studied the fate of Lgr5+ HFSCs after SCT and explored the novel treatment to protect Lgr5+ HFSCs against GVHD using murine models of SCT. We found that GVHD reduced Lgr5+ HFSCs in association with impaired hair regeneration and wound healing in the skin after SCT. Topical corticosteroids, a standard of care for a wide range of skin disorders including GVHD, damaged HFSCs and failed to improve skin homeostasis, despite of their anti-inflammatory effects. In contrast, JAK1/2 inhibitor ruxolitinib significantly ameliorated skin GVHD, protected Lgr5+ HFSCs, and restored hair regeneration and wound healing after SCT. We, for the first time, found that GVHD targets Lgr5+ HFSCs and that topical ruxolitinib represents a novel strategy to protect skin stem cells and maintain skin homeostasis in GVHD.
Asunto(s)
Enfermedad Injerto contra Huésped/etiología , Homeostasis , Inhibidores de Proteínas Quinasas/farmacología , Pirazoles/farmacología , Fenómenos Fisiológicos de la Piel , Células Madre/citología , Células Madre/metabolismo , Corticoesteroides/administración & dosificación , Animales , Biopsia , Epitelio/efectos de los fármacos , Epitelio/metabolismo , Enfermedad Injerto contra Huésped/diagnóstico , Enfermedad Injerto contra Huésped/prevención & control , Folículo Piloso/citología , Ratones , Nitrilos , Pirimidinas , Trasplante de Células Madre/efectos adversos , Células Madre/efectos de los fármacosRESUMEN
Although a combination of calcineurin inhibitor and methotrexate (MTX) is used for graft-versus-host disease (GVHD) prophylaxis in umbilical cord blood transplantation (CBT), optimal dose of MTX for CBT remains to be determined.We conducted a retrospective study to evaluate the safety and efficacy of standard-dose MTX (St-MTX, 15 mg/m2 on day 1 and 10 mg/m2 on days 3 and 6) and mini-dose MTX (Mini-MTX, 5 mg/m2 on days 1, 3 and 6) for GVHD prophylaxis in patients who underwent single unit CBT against hematological malignancies.Thirty-two and 26 patients received St-MTX and Mini-MTX, respectively. Cumulative incidence of neutrophil engraftment was significantly higher in the Mini-MTX group than in the St-MTX group (88.5% vs 65.6%, P = 0.00448). Cumulative incidences of grade II to IV and grade III to IV of acute graft-versus-host disease (GVHD) were 34.4% and 6.2% in the St-MTX group, and 34.6% and 7.7% in the Mini-MTX group with no statistical significance. One-year non-relapse mortality (NRM) was significantly lower in the Mini-MTX group compared to the St-MTX group (31.2% vs 3.8%, P = 0.00938), whereas relapse rate was not different between the groups. Multivariate analysis also indicated that Mini-MTX significantly improved engraftment (HR, 0.5359; 95% CI, 0.3082 to 0.9318; P = 0.0270) and reduced NRM (HR, 0.117; 95% CI, 0.0151 to 0.9067; P = 0.040).Our study suggests that GVHD prophylaxis using Mini-MTX in CBT is feasible and associated with improvement of engraftment and reduction in NRM.