Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 381
Filtrar
1.
Diagnostics (Basel) ; 14(17)2024 Aug 29.
Artículo en Inglés | MEDLINE | ID: mdl-39272689

RESUMEN

Serum erythropoietin (sEPO) is an initial screening tool for distinguishing polycythemia vera (PV) from secondary erythrocytosis (SE), but defining 'subnormal' sEPO levels for PV diagnosis remains contentious, complicating its clinical utility. This study compares the diagnostic performance of sEPO across established subnormal limits, including reference interval (RI), clinical decision limit (CDL), and functional reference limit. sEPO levels were analyzed in 393 healthy donors (HDs) and 90 patients (41 PV and 49 SE), who underwent bone marrow biopsy and genetic tests due to erythrocytosis. The RI (2.5-97.5 percentile from HDs) of sEPO was 5.3-26.3 IU/L. A CDL of 3.1 IU/L, determined by ROC analysis in erythrocytosis patients, had a sensitivity of 80.5% and specificity of 87.8% for diagnosing PV. A functional reference limit of 7.0 IU/L, estimated based on the relationship between sEPO and hemoglobin, hematocrit, and WBC, increased sensitivity to 97.6% but decreased specificity to 46.7%. Using 5.3 IU/L as a 'subnormal' limit identified all three JAK2-negative PV cases, increasing the sensitivity and negative predictive value to 97.6% and 97.0%, respectively. Combining the RI, CDL, and functional reference limit may improve PV diagnostic accuracy.

2.
Molecules ; 29(17)2024 Aug 26.
Artículo en Inglés | MEDLINE | ID: mdl-39274884

RESUMEN

Prion diseases, known as a group of fatal neurodegenerative disorders caused by prions, remain incurable despite extensive research efforts. In a recent study, crude extract from Curcuma phaeocaulis Valeton (Cp) showed promising anti-prion efficacy in in vitro and in vivo models, prompting further investigation into their active compounds. We endeavored to identify the chemical constituents of the Cp extract and discover potential anti-prion agents. With the use of centrifugal partition chromatography (CPC), major constituents were isolated from the n-hexane (HX) fraction of the extract in a single step. Spectroscopic analysis confirmed the presence of curcumenone, curcumenol, and furanodienone. Subsequent efficacy testing in a cell culture model of prion disease identified curcumenol and furanodienone as active compounds. This study underscores the potential of natural products in the search for effective treatments against prion diseases.


Asunto(s)
Curcuma , Extractos Vegetales , Curcuma/química , Extractos Vegetales/química , Extractos Vegetales/farmacología , Animales , Priones/antagonistas & inhibidores , Enfermedades por Prión/tratamiento farmacológico , Ratones , Humanos , Sesquiterpenos/farmacología , Sesquiterpenos/química , Sesquiterpenos/aislamiento & purificación
3.
Medicine (Baltimore) ; 103(37): e39532, 2024 Sep 13.
Artículo en Inglés | MEDLINE | ID: mdl-39287314

RESUMEN

RATIONALE: Stress-induced cardiomyopathy (SCMP), also known as Takotsubo syndrome, is a transient cardiac condition often precipitated by severe emotional or physical stress. It is commonly mistaken for acute coronary syndrome due to similar clinical presentations. The use of point-of-care ultrasound (POCUS) provides a noninvasive, rapid diagnostic alternative that can potentially reduce the need for invasive coronary angiography, especially in emergency settings. PATIENT CONCERNS: A 26-year-old woman with type 1 diabetes presented to the emergency department following a suicidal hanging attempt. Upon arrival, she was conscious but confused, with stable vital signs. There were visible signs of strangulation, but no other immediate physical abnormalities. Laboratory tests revealed elevated cardiac enzymes and hyperglycemia. DIAGNOSES: Initial bedside POCUS revealed a reduced ejection fraction and regional wall motion abnormalities in the midportion of the left ventricle, suggesting SCMP. These findings, combined with the patient's history and absence of other contributory factors, led to a provisional diagnosis of SCMP. INTERVENTIONS: The patient was admitted to the intensive care unit for close monitoring. Serial POCUS examinations were performed to track cardiac function. Due to the rapid improvement in regional wall motion abnormalities observed through POCUS, the planned coronary angiography was deferred. OUTCOMES: The patient exhibited significant clinical improvement within 24 hours, with normalization of cardiac function as demonstrated by follow-up POCUS. Cardiac enzyme levels also returned to normal. The patient was discharged directly from the intensive care unit without the need for further invasive procedures. LESSONS: This case underscores the diagnostic value of POCUS in rapidly identifying SCMP in emergency settings, which can guide timely and appropriate management. The noninvasive nature of POCUS may reduce the need for invasive diagnostics, minimize hospital stay duration, and enhance cost-effectiveness in managing SCMP.


Asunto(s)
Sistemas de Atención de Punto , Cardiomiopatía de Takotsubo , Humanos , Femenino , Cardiomiopatía de Takotsubo/diagnóstico , Cardiomiopatía de Takotsubo/etiología , Adulto , Ultrasonografía/métodos , Intento de Suicidio
4.
Diagnostics (Basel) ; 14(16)2024 Aug 12.
Artículo en Inglés | MEDLINE | ID: mdl-39202234

RESUMEN

Hepatic graft-versus-host disease (GVHD) significantly impacts morbidity and mortality among allogeneic hematopoietic stem cell transplant recipients. However, the relationship between clinical and immunopathological phenotypes and their influence on clinical outcomes in hepatic GVHD is not well understood. In this study, we aimed to study the implications of portal T-cell infiltration on the clinical outcomes in hepatic GHVD and its similarities to autoimmune liver disease. We analyzed 78 patients with biopsy-confirmed hepatic GVHD (n = 38) or autoimmune liver disease (n = 40) between 2016 and 2021. The cholestatic variant was defined by an R-value < 2.0, based on the ratio of alanine aminotransferase to alkaline phosphatase. The primary outcome was the biochemical response at 4 (early) and 8-12 (late) weeks after corticosteroid treatment. In hepatic GVHD patients, the hepatitic variant (n = 19) showed greater CD3+ T-cell infiltration than the cholestatic variant (n = 19; p < 0.001). No significant differences were observed in the infiltration of CD20+, CD38+, or CD68+ cells. The hepatitic variant had significantly better early and late responses and higher liver-related event-free survival than the cholestatic variants (p < 0.05). Concerning autoimmune liver diseases, the autoimmune hepatitis (AIH) group had significantly more portal T-cell infiltration and better treatment responses than the primary biliary cholangitis (PBC) group. In conclusion, higher portal T-cell infiltration may be associated with better clinical outcomes in patients with hepatic GVHD. Additionally, this study highlights similarities in portal T-cell infiltration and treatment response patterns between AIH and the hepatitic variant, as well as PBC and the cholestatic variant.

6.
Artículo en Inglés | MEDLINE | ID: mdl-38997400

RESUMEN

Reduced-toxicity conditioning (RTC) regimens aim to mitigate regimen-related toxicity while maintaining anti-leukemic efficacy in allogeneic hematopoietic stem cell transplantation (allo-HSCT). We assessed outcomes of RTC regimens utilizing melphalan versus intravenous busulfan combined with fludarabine in adult acute lymphoblastic leukemia (ALL) patients. A retrospective analysis was conducted with 149 consecutive adult ALL patients (median age 51, range 18-60) in remission undergoing allo-HSCT. Patients received either fludarabine 150 mg/BSA plus 2 days of melphalan 70 mg/BSA (FM140, n = 76) from 2009 to 2015 or fludarabine plus 3 days of busulfan 3.2 mg/kg (FB9.6, n = 73) from 2016 to 2021. At 5 years post-HSCT, FM140 demonstrated superior disease-free survival (53.4% vs. 30.5%, p = 0.007) and lower cumulative relapse (27.4% vs. 46.8%, p = 0.026) than FB9.6. Five-year overall survival and non-relapse mortality did not significantly differ. FM140 exhibited a higher incidence of acute graft-versus-host disease (GVHD) grades II-IV (49.3% vs. 30.3%, p = 0.016), though rates of acute GVHD grades III-IV and chronic GVHD were similar. Multivariate analysis identified Philadelphia chromosome and minimal residual disease positive status, and FB9.6 conditioning as predictors of increased relapse and poorer disease-free survival. FM140 RTC regimen displayed significantly reduced relapse and superior disease-free survival compared to FB9.6 in ALL patients undergoing allo-HSCT, highlighting its current clinical utility.

7.
J Med Chem ; 67(13): 10601-10621, 2024 Jul 11.
Artículo en Inglés | MEDLINE | ID: mdl-38896548

RESUMEN

Inflammatory bowel disease (IBD) is characterized by abnormal immune responses, including elevated proinflammatory cytokines, such as tumor necrosis factor-α (TNFα) and interleukin-6 (IL-6) in the gastrointestinal (GI) tract. This study presents the synthesis and anti-inflammatory evaluation of 2,4,5-trimethylpyridin-3-ol analogues, which exhibit dual inhibition of TNFα- and IL-6-induced inflammation. Analysis using in silico methods, including 3D shape-based target identification, modeling, and docking, identified G protein-coupled estrogen receptor 1 (GPER) as the molecular target for the most effective analogue, 6-26, which exhibits remarkable efficacy in ameliorating inflammation and restoring colonic mucosal integrity. This was further validated by surface plasmon resonance (SPR) assay results, which showed direct binding to GPER, and by the results showing that GPER knockdown abolished the inhibitory effects of 6-26 on TNFα and IL-6 actions. Notably, 6-26 displayed no cytotoxicity, unlike G1 and G15, a well-known GPER agonist and an antagonist, respectively, which induced necroptosis independently of GPER. These findings suggest that the GPER-selective compound 6-26 holds promise as a therapeutic candidate for IBD.


Asunto(s)
Enfermedades Inflamatorias del Intestino , Receptores de Estrógenos , Receptores Acoplados a Proteínas G , Receptores Acoplados a Proteínas G/antagonistas & inhibidores , Receptores Acoplados a Proteínas G/metabolismo , Receptores Acoplados a Proteínas G/agonistas , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Enfermedades Inflamatorias del Intestino/metabolismo , Humanos , Animales , Receptores de Estrógenos/metabolismo , Receptores de Estrógenos/antagonistas & inhibidores , Mucosa Intestinal/metabolismo , Mucosa Intestinal/efectos de los fármacos , Mucosa Intestinal/patología , Interleucina-6/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo , Ratones , Simulación del Acoplamiento Molecular , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico , Antiinflamatorios/química , Antiinflamatorios/síntesis química , Piridinas/farmacología , Piridinas/síntesis química , Piridinas/química , Piridinas/uso terapéutico , Ratones Endogámicos C57BL , Relación Estructura-Actividad
8.
J Hazard Mater ; 472: 134445, 2024 Jul 05.
Artículo en Inglés | MEDLINE | ID: mdl-38701727

RESUMEN

The prevalence of microplastic (MP) contamination has become a significant environmental concern due to its pervasive nature and persistent effects. While sediments are considered major repositories for MPs, information on their spatial distribution within these matrices is insufficient. This research examined both the horizontal and vertical presence of MPs in the sediments surrounding Lake Paldang in South Korea, alongside a comprehensive evaluation of the physicochemical characteristics of the samples obtained. The total content of MPs varied from 2.15 to 122.2 particles g-1. The average contents of MPs on surface sediments were 40.47, 34.14, 5.01, and 8.19 particles g-1 in north mainstream (NM), south mainstream (SM), tributary (TB), and Tributary catchment (TC) based on Sonae Island, Gyeongan stream, respectively. The most abundant MP types were polyethylene (PE), polytetrafluoroethylene (PTFE), and polypropylene (PP), accounting for more than 70% of the total MPs. The most abundant sizes of MPs were within 45-100 µm. At all sediment depths, polymers were distributed in the order PE, PP, and polyester in NM, SM, and TC, respectively, whereas PTFE mainly occurred in the surface layer. MPs distribution also exhibited seasonal variation as larger inflows and flow rates varied with season.

9.
Cureus ; 16(2): e54206, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38496121

RESUMEN

INTRODUCTION: Patients with hematological diseases experience complications related to portal hypertension, including life-threatening complications such as variceal bleeding. METHODS: We analyzed the prognosis of patients with hematological diseases and portal hypertension treated with transjugular intrahepatic portosystemic shunts (TIPS) or portal vein stents. We retrospectively assessed patients with hematological diseases and portal hypertension who had variceal bleeding. We evaluated the characteristics and prognosis of the enrolled patients. A total of 11 patients with hematological diseases who underwent TIPS, or portal vein stenting, were evaluated. RESULTS: The median follow-up period was 420 days. Of the 11 patients, eight showed resolution of portal hypertension and its complications following TIPS, or stent insertion. One patient experienced rebleeding due to incomplete resolution of portal hypertension, and two other patients also experienced rebleeding because they underwent TIPS closure or revision due to repetitive hepatic encephalopathy. CONCLUSION: Portosystemic shunt and stent installation are effective treatment options for portal hypertension due to hematological diseases.

10.
J Clin Lab Anal ; 38(7): e25034, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38525919

RESUMEN

BACKGROUND: Accurate quantification of the BCR::ABL1 transcripts is essential for measurable residual disease (MRD) monitoring in chronic myeloid leukemia (CML) after tyrosine kinase inhibitor (TKI) treatment. This study evaluated the newly developed digital real-time PCR method, Dr. PCR, as an alternative reverse transcription-PCR (qRT-PCR) for MRD detection. METHODS: The performance of Dr. PCR was assessed using reference and clinical materials. Precision, linearity, and correlation with qRT-PCR were evaluated. MRD levels detected by Dr. PCR were compared with qRT-PCR, and practical advantages were investigated. RESULTS: Dr. PCR detected MRD up to 0.0032%IS (MR4.5) with excellent precision and linearity and showed a strong correlation with qRT-PCR results. Notably, Dr. PCR identified higher levels of MRD in 12.7% (29/229) of patients than qRT-PCR, including six cases of MR4, which is a critical level for TKI discontinuation. Dr. PCR also allowed for sufficient ABL1 copies in all cases, while qRT-PCR necessitated multiple repeat tests in 3.5% (8/229) of cases. CONCLUSION: Our study provides a body of evidence supporting the clinical application of Dr. PCR as a rapid and efficient method for assessing MRD in patients with CML under the current treatment regimen.


Asunto(s)
Proteínas de Fusión bcr-abl , Leucemia Mielógena Crónica BCR-ABL Positiva , Neoplasia Residual , Reacción en Cadena en Tiempo Real de la Polimerasa , Humanos , Reacción en Cadena en Tiempo Real de la Polimerasa/métodos , Proteínas de Fusión bcr-abl/genética , Leucemia Mielógena Crónica BCR-ABL Positiva/genética , Leucemia Mielógena Crónica BCR-ABL Positiva/tratamiento farmacológico , Neoplasia Residual/genética , Reproducibilidad de los Resultados
11.
Bone Marrow Transplant ; 59(6): 813-823, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38438648

RESUMEN

In the present study, reduced toxicity (FluBu3) and myeloablative (BuCy) conditioning were compared in patients with AML who received first allogeneic HSCT in MRD-negative CR1. The study included 124 adult patients who underwent HSCT from an HLA-matched (8/8) sibling, unrelated, or 1-locus mismatched (7/8) unrelated donor (MMUD). The median age was 45 years and intermediate cytogenetics comprised majority (71.8%). The 2-year OS, RFS, CIR and NRM for BuCy (n = 78, 62.9%) and FluBu3 (n = 46, 37.1%) groups were 78.3% and 84.5% (p = 0.358), 78.0% and 76.3% (p = 0.806), 7.7% and 21.5% (p = 0.074) and 14.3% and 2.2% (p = 0.032), respectively. At the time of data cut-off, relapse and NRM were the main causes of HSCT failure in each of the FluBu3 and BuCy arms. Among patients, 75% of relapsed FluBu3 patients had high-risk features of either poor cytogenetics or FLT3-ITD mutation compared with 16.7% of BuCy patients. The majority of NRM in the BuCy group was due to GVHD (73%), half of whom received MMUD transplantation. To conclude, the FluBu3 reduced toxicity conditioning showed comparable post-transplant OS and RFS to BuCy and was associated with significantly reduced NRM that was offset by a trend towards higher risk of relapse even in MRD-negative CR1 population.


Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Leucemia Mieloide Aguda , Acondicionamiento Pretrasplante , Humanos , Acondicionamiento Pretrasplante/métodos , Leucemia Mieloide Aguda/terapia , Leucemia Mieloide Aguda/mortalidad , Persona de Mediana Edad , Trasplante de Células Madre Hematopoyéticas/métodos , Masculino , Femenino , Adulto , Neoplasia Residual , Trasplante Homólogo/métodos , Anciano , Adolescente , Adulto Joven , Agonistas Mieloablativos/uso terapéutico , Aloinjertos
12.
J Plant Physiol ; 293: 154182, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38277982

RESUMEN

Maintenance of energy metabolism is critical for rice (Oryza sativa) tolerance under submerged cultivation. Here, OsHXK7 was the most actively induced hexokinase gene in the embryos of hypoxically germinating rice seeds. Suspension-cultured cells established from seeds of T-DNA null mutants for the OsHXK7 locus did not regrow after 3-d-hypoxic stress and showed increased susceptibility to low-oxygen stress-in terms of viability-and decreased alcoholic fermentation activities compared to those of the wild-type. The promoter element containing the TGACG-motif, a well-known target site for the basic leucine zipper (bZIP) transcription factors, was responsible for sugar regulation of the OsHXK7 promoter activity. Systematic screening of the OsbZIP genes showing the similar expression patterns to that of OsHXK7 in the transcriptomic datasets produced two bZIP genes, OsbZIP38 and 87, belonging to the S1 bZIP subfamily as the candidate for the activator for this gene expression. Gain- and loss-of-function experiments through transient expression assays have demonstrated that these two bZIP proteins are indeed involved in the induction of OsHXK7 expression under starvation or low-energy conditions. Our finding suggests that C/S1 bZIP network-mediated hypoxic deregulation of sugar-responsive genes may work in concert for the molecular adaptation of rice cells to submergence.


Asunto(s)
Oryza , Oryza/metabolismo , Perfilación de la Expresión Génica , Regiones Promotoras Genéticas , Semillas/genética , Semillas/metabolismo , Azúcares/metabolismo , Regulación de la Expresión Génica de las Plantas , Proteínas de Plantas/metabolismo , Factores de Transcripción con Cremalleras de Leucina de Carácter Básico/genética , Factores de Transcripción con Cremalleras de Leucina de Carácter Básico/metabolismo
13.
J Korean Med Sci ; 39(3): e24, 2024 Jan 22.
Artículo en Inglés | MEDLINE | ID: mdl-38258361

RESUMEN

BACKGROUND: Previous studies have suggested that patients with polycythemia vera (PV) who exhibit hydroxyurea-resistance (HU-R) and -intolerance (HU-I) may have distinct characteristics and clinical outcomes. However, to date, no studies have reported a comparison between these two groups or assessed prognostic factors in these patients. METHODS: The objective of this study was to evaluate clinical outcomes and identify prognostic factors among PV patients with HU-R or HU-I. We conducted a review of PV patients who received frontline treatment with HU from nine centers and identified 90 patients with HU-R or HU-I. RESULTS: The cumulative incidence of thrombosis after 7 years of HU-R/I was 21.4%, and the incidence of disease progression was 22.5%. Comparing the HU-R and HU-I groups, the HU-R group had a significantly higher rate of disease progression (36.7% vs. 0.56%, P = 0.009), while there was no significant difference in thrombosis incidence (19.0% vs. 22.9%, P = 0.463). Multivariate analysis revealed that HU-R was an independent prognostic factor for progression-free survival (hazard ratio, 6.27, 95% confidence interval, 1.83-21.47, P = 0.003). Additionally, higher lactate dehydrogenase levels, multiple cardiovascular risk factors, and prior thrombosis were identified as unfavorable predictors of overall survival. CONCLUSION: These findings suggest that patients with HU-R face a higher risk of hematological transformation, but have a comparable risk of thrombosis to patients with HU intolerance. These distinctions should guide decisions on second-line treatment options and clinical trials involving these patients.


Asunto(s)
Hidroxiurea , Policitemia Vera , Humanos , Progresión de la Enfermedad , Factores de Riesgo de Enfermedad Cardiaca , Hidroxiurea/farmacología , Policitemia Vera/tratamiento farmacológico , Trombosis/epidemiología , Estudios Retrospectivos
14.
Front Oncol ; 13: 1281782, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38023260

RESUMEN

Introduction: Intensive chemotherapy (IC) can affect all geriatric assessment (GA) domains in older adults with acute myeloid leukemia (AML), but data on the effects of these changes on transplant outcomes are lacking. Methods: Therefore, we prospectively assessed the prognostic role of GA domains at diagnosis and allogeneic hematopoietic stem cell transplantation (allo-HSCT) in 51 patients with AML aged ≥60 years who achieved complete remission after IC. We performed both baseline and pre-allo-HSCT GA; moreover, physical function, including a short physical performance battery (SPPB), cognitive function, psychological function, nutritional status, and social support were examined. Results: All GA domains showed dynamic changes between the two time points. The directions of change were statistically significant for social support, self-reported physical and psychological functions, and distress, but not for nutritional status, cognitive function, or physical function. Among all GA domains at each time point, only poor physical function and its submaneuvers at diagnosis but not at allo-HSCT were significantly associated with inferior survival. In particular, since the direction of change varied between patients, we found that patients whose physical function improved before allo-HSCT were more likely to survive longer than those with persistently impaired SPPB (55.6% vs. 28.6%, p=0.268). Finally, persistent impairment in SPPB (28.6% vs. 65.9%, p=0.006), tandem stand (0% vs. 63.3%, p=0.012), sit-and-stand (41.2% vs. 70.6%, p=0.009), and gait speed (38.5% vs. 68.4%, p=0.027) further strongly predicted inferior survival. Discussion: This study showed that IC courses can induce dynamic changes in different directions in the GA domains of each patient and that changes in objectively measured physical function can predict transplant outcomes.

15.
Sci Rep ; 13(1): 17496, 2023 10 15.
Artículo en Inglés | MEDLINE | ID: mdl-37840059

RESUMEN

To clarify the role of allogeneic hematopoietic stem-cell transplantation (allo-HSCT) in the chimeric antigen receptor T-cell therapy era, we analyzed the clinical characteristics and outcomes of 52 patients treated with allo-HSCT with relapsed/refractory diffuse large B cell lymphoma. Most enrolled patients had previously undergone intensive treatments, the median number of chemotherapy lines was 4, and the median time from diagnosis to allo-HSCT was 27.1 months. Patients were divided into remission-achieved (n = 30) and active-disease (n = 22) groups before allo-HSCT. Over a median follow-up period of 38.3 months, overall survival (OS) and event-free survival (EFS) rates were 38.4% and 30.6%, respectively. The cumulative incidence of relapse (CIR) and the non-relapsed mortality (NRM) were 36.7% and 32.7%, respectively. OS, EFS, and graft-versus-host disease-free, relapse-free survival (GRFS) outcomes were significantly superior in the remission-achieved group with lower CIR. In a multivariate analysis, a shorter interval from diagnosis to allo-HSCT reflected relatively rapid disease progression and showed significantly poor OS and EFS with higher CIR. Patients with active disease had significantly lower EFS, GRFS, and higher CIR. Previous autologous stem-cell transplantation was associated with better GRFS. Allo-HSCT is an established modality with a prominent group of cured patients and still has a role in the CAR T-cell era, particularly given its acceptable clinical outcomes in young patients with chemo-susceptible disease.


Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Linfoma de Células B Grandes Difuso , Linfoma no Hodgkin , Humanos , Supervivencia sin Enfermedad , Recurrencia Local de Neoplasia/terapia , Linfoma no Hodgkin/terapia , Linfoma de Células B Grandes Difuso/terapia , Estudios Retrospectivos
16.
Respir Med ; 218: 107410, 2023 11.
Artículo en Inglés | MEDLINE | ID: mdl-37696312

RESUMEN

BACKGROUND: Bronchiolitis obliterans syndrome (BOS) is the lung manifestation of chronic graft-versus-host disease after hematopoietic stem cell transplantation (HSCT). We assessed whether inhaled tiotropium add-on to the combination regimen including budesonide/formoterol improve pulmonary function and the chronic obstructive pulmonary disease assessment test (CAT) scores in patients with BOS. METHODS: Post-HSCT patients diagnosed as BOS in Seoul St. Mary's Hospital were reviewed retrospectively. Patients defined as BOS and treated with budesonide/formoterol/tiotropium combination therapy after budesonide/formoterol therapy from January 2011 to June 2019 were enrolled. RESULTS: Total of 86 patients were evaluated. After tiotropium add-on, the absolute FEV1 increased significantly from 1.47 ± 0.49 to 1.53 ± 0.57 L (p = 0.023) and the % predicted FEV1 from 45.0 ± 12.8 to 46.8 ± 14.5% (p = 0.031). The % predicted DLCO increased significantly after tiotropium add-on (from 61.6 ± 16.7 to 64.3 ± 16.3%, p = 0.028). Among 56 patients with complete CAT scores, no significant change was present in total CAT scores. In all, 30 of the 72 patients (41.7%) evidenced FEV1 increases > 100 mL, and 20 of 56 patients (35.7%) had CAT score decreases of ≥ 2 points. When the FEV1 and CAT scores were combined, the overall response rate to tiotropium add-on was 56.2% (41/73). The response group evidenced a significantly greater FVC increase, and a significant decrease in the RV/TLC ratio compared to the no-response group. CONCLUSIONS: Inhaled tiotropium add-on to combination budesonide/formoterol significantly improved lung function, but not respiratory symptoms, in patients with post-HSCT BOS.


Asunto(s)
Bronquiolitis Obliterante , Trasplante de Células Madre Hematopoyéticas , Enfermedad Pulmonar Obstructiva Crónica , Humanos , Bromuro de Tiotropio/uso terapéutico , Budesonida/uso terapéutico , Estudios Retrospectivos , Bronquiolitis Obliterante/tratamiento farmacológico , Bronquiolitis Obliterante/etiología , Combinación Budesonida y Fumarato de Formoterol/uso terapéutico , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Broncodilatadores
17.
Viruses ; 15(9)2023 09 06.
Artículo en Inglés | MEDLINE | ID: mdl-37766290

RESUMEN

The prevention and management of cytomegalovirus (CMV) reactivation is important to improve the outcomes of allogeneic hematopoietic cell transplantation (allo-HCT) recipients. The aim of this study was to analyze real-world data regarding the incidence and characteristics of CMV infections until 1 year after allo-HCT under 100-day letermovir prophylaxis. A single-center retrospective study was conducted between November 2020 and October 2021. During the study period, 358 patients underwent allo-HCT, 306 of whom received letermovir prophylaxis. Cumulative incidence of clinically significant CMV infection (CS-CMVi) was 11.4%, 31.7%, and 36.9% at 14 weeks, 24 weeks, and 1 year post-HCT, respectively. Through multivariate analysis, the risk of CS-CMVi increased with graft-versus-host disease (GVHD) ≥ grade 2 (adjusted odds ratio 3.640 [2.036-6.510]; p < 0.001). One-year non-relapse mortality was significantly higher in letermovir breakthrough CS-CMVi patients than those with subclinical CMV reactivation who continued receiving letermovir (p = 0.002). There were 18 (15.9%) refractory CMV infection cases in this study population. In summary, letermovir prophylaxis is effective at preventing CS-CMVi until day 100, which increased after the cessation of letermovir. GVHD is still a significant risk factor in the era of letermovir prophylaxis. Further research is needed to establish individualized management strategies, especially in patients with significant GVHD or letermovir breakthrough CS-CMVi.


Asunto(s)
Infecciones por Citomegalovirus , Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Humanos , Estudios de Seguimiento , Estudios Retrospectivos , Infecciones por Citomegalovirus/epidemiología , Infecciones por Citomegalovirus/etiología , Infecciones por Citomegalovirus/prevención & control , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Enfermedad Injerto contra Huésped/prevención & control
18.
Toxins (Basel) ; 15(9)2023 09 16.
Artículo en Inglés | MEDLINE | ID: mdl-37755997

RESUMEN

Fungal infection and mycotoxin contamination are major hazards to the safe storage and distribution of foods and feeds consumed by humans and livestock. This study investigated the antifungal and antiaflatoxigenic activities of massoia essential oil (MEO) and its major constituent, C10 massoia lactone (C10), against aflatoxin B (AFB)-producing Aspergillus flavus ATCC 22546. Their antifungal activities were evaluated using a disc diffusion assay, agar dilution method, and a mycelial growth inhibition assay with the AFB analysis using liquid chromatography triple quadrupole mass spectrometry. MEO and C10 exhibited similar antifungal and antiaflatoxigenic activities against A. flavus. C10 was a primary constituent in MEO and represented up to 45.1% of total peak areas analyzed by gas chromatography-mass spectrometry, indicating that C10 is a major compound contributing to the antifungal and antiaflatoxigenic activities of MEO. Interestingly, these two materials increased AFB production in A. flavus by upregulating the expression of most genes related to AFB biosynthesis by 3- to 60-fold. Overall, MEO and C10 could be suitable candidates as natural preservatives to control fungal infection and mycotoxin contamination in foods and feeds as Generally Recognized As Safe (GRAS) in the Flavor and Extract Manufacturers Association of the United States (FEMA), and MEO is a more suitable substance than C10 because of its wider range of uses and higher allowed concentration than C10.


Asunto(s)
Aflatoxinas , Micotoxinas , Humanos , Aspergillus flavus , Antifúngicos/farmacología , Aflatoxina B1/toxicidad , Lactonas/farmacología
19.
Microorganisms ; 11(8)2023 Aug 18.
Artículo en Inglés | MEDLINE | ID: mdl-37630666

RESUMEN

An intermittent fasting regimen is widely perceived to lead to various beneficial health effects, including weight loss, the alleviation of insulin resistance, and the restructuring of a healthy gut microbiome. Because it shares certain commonalities with this dietary intervention, Ramadan fasting is sometimes misinterpreted as intermittent fasting, even though there are clear distinctions between these two regimens. The main purpose of this study is to verify whether Ramadan fasting drives the same beneficial effects as intermittent fasting by monitoring alterations in the gut microbiota. We conducted a study involving 20 Muslim individuals who were practicing Ramadan rituals and assessed the composition of their gut microbiomes during the 4-week period of Ramadan and the subsequent 8-week period post-Ramadan. Fecal microbiome analysis was conducted, and short-chain fatty acids (SCFAs) were assessed using liquid-chromatography-mass spectrometry. The observed decrease in the levels of SCFAs and beneficial bacteria during Ramadan, along with the increased microbial diversity post-Ramadan, suggests that the daily diet during Ramadan may not provide adequate nutrients to maintain robust gut microbiota. Additionally, the notable disparities in the functional genes detected through the metagenomic analysis and the strong correlation between Lactobacillus and SCFAs provide further support for our hypothesis.

20.
Cytotherapy ; 25(12): 1307-1316, 2023 12.
Artículo en Inglés | MEDLINE | ID: mdl-37542512

RESUMEN

BACKGROUND AIMS: Peripheral T-cell lymphomas (PTCLs) are rare and aggressive tumors with uncertain optimal treatment. This study investigated the clinical outcomes of high-dose chemotherapy (HDT) followed by autologous stem cell transplantation (ASCT) after CD34+ selective purging in PTCL patients. METHODS: Retrospective analysis included 67 PTCL patients who achieved remission and underwent HDT/ASCT. CD34+ selective purging was performed using CliniMACS® (Miltenyi Biotec, Bergisch Gladbach, Germany). Survival outcomes, engraftment, lymphocyte subsets and viral infections were evaluated. RESULTS: CD34+ selective purged autografts were associated with significantly improved overall survival (OS) and disease-free survival (DFS) compared with unpurged autografts (5-year OS, 73.3% versus 37.8%, 5-year DFS, 73.8% versus 33.4%). The cumulative incidence of relapse was also lower in the purged group (31.5% versus 73.3%). Subgroup analysis revealed significant survival benefits in the high-risk group receiving purged autografts. Lymphocyte subset analysis showed increased natural killer (NK) cell counts in the purged group after ASCT. Higher post-ASCT lymphocyte-to-monocyte ratio (LMR) was associated with improved OS and DFS. CONCLUSIONS: CD34+ selective purging in PTCL patients undergoing HDT/ASCT improved survival outcomes and reduced relapse risk. The procedure increased NK cell counts and post-ASCT LMR. CD34+ selective purging may minimize autograft tumor cell contamination and enhance efficacy in T-cell lymphomas.


Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Linfoma de Células T Periférico , Humanos , Linfoma de Células T Periférico/terapia , Trasplante Autólogo , Estudios Retrospectivos , Recurrencia Local de Neoplasia , Antígenos CD34 , Moléculas de Adhesión Celular , Recurrencia
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA
...