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1.
BMC Womens Health ; 24(1): 455, 2024 Aug 13.
Artículo en Inglés | MEDLINE | ID: mdl-39138442

RESUMEN

BACKGROUND: Appropriate physical activity (PA) and good sleep are beneficial to maternal and fetal health. This paper sought to explore the associations of PA and sleep quality among healthy women at the first and second trimesters of pregnancy on mental health and pregnancy outcomes. METHODS: Totally 268 healthy pregnant women were retrospectively analyzed as study subjects, 134 each in the first trimester (FT) and second trimester (ST). Their baseline clinical data were obtained respectively at two stages of pregnancy. The PA/sleep quality of subjects were assessed through the Pregnancy Physical Activity Questionnaire-Chinese version (PPAQ-C)/Pittsburgh Sleep Quality Index (PSQI) scale. The mental health was assessed via the Hospital Anxiety and Depression Scale (HADS). The correlations of PA and sleep quality with mental health were analyzed using Spearman correlation analysis. Pregnancy outcomes of all subjects, associations of moderate intensity (MI) PA and sleep quality with adverse pregnancy outcomes, and independent influencing factors for adverse outcomes were analyzed. RESULTS: Pregnant women in the ST group exhibited higher levels of MI, worse sleep quality, and lower levels of anxiety and depression than those in the FT group. Anxiety and depression were negatively correlated with MI but positively linked with PSQI scores at the first and second trimesters. MI ≥ 7.5 MET-h/week and good sleep quality were associated with a reduced incidence of adverse pregnancy outcomes. CONCLUSION: MI ≥ 7.5 MET-h/week and good sleep quality at the first and second trimesters of pregnancy benefit mental health and markedly reduce the occurrence of adverse pregnancy outcomes.


Asunto(s)
Ansiedad , Depresión , Ejercicio Físico , Salud Mental , Resultado del Embarazo , Primer Trimestre del Embarazo , Segundo Trimestre del Embarazo , Calidad del Sueño , Humanos , Femenino , Embarazo , Adulto , Segundo Trimestre del Embarazo/psicología , Ejercicio Físico/psicología , Ejercicio Físico/fisiología , Estudios Retrospectivos , Salud Mental/estadística & datos numéricos , Primer Trimestre del Embarazo/psicología , Depresión/psicología , Depresión/epidemiología , Ansiedad/psicología , Ansiedad/epidemiología , Resultado del Embarazo/epidemiología , Encuestas y Cuestionarios , Complicaciones del Embarazo/psicología , Complicaciones del Embarazo/epidemiología , Mujeres Embarazadas/psicología , China/epidemiología
2.
PeerJ ; 12: e17627, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38978753

RESUMEN

Background: The Minqin Oasis, which is located in Wuwei City, Gansu Province, China, faces a very serious land desertification problem, with about 94.5% of its total area desertified. Accordingly, it is crucial to implement ecological restoration policies such as cropland abandonment in this region. In abandoned croplands, abiotic factors such as soil properties may become more important than biotic factors in driving vegetation succession. However, the connections between soil properties and vegetation succession remain unclear. To fill this knowledge gap, this study investigated these connections to explore major factors that affected vegetation succession, which is meaningful to designing management measures to restore these degraded ecosystems. Methods: This study investigated seven 1-29-year-old abandoned croplands using the "space for time" method in Minqin Oasis. Vegetation succession was classified into different stages using a canonical correlation analysis (CCA) and two-way indicator species analysis (Twinspan). The link between soil properties and vegetation succession was analyzed using CCA. The primary factors shaping community patterns of vegetation succession were chosen by the "Forward selection" in CCA. The responses of dominant species to soil properties were analyzed using generalized additive models (GAMs). Results: Dominant species turnover occurred obviously after cropland abandonment. Vegetation succession can be classified into three stages (i.e., early, intermediate, and late successional stages) with markedly different community composition and diversity. The main drivers of vegetation succession among soil properties were soil salinity and saturated soil water content and they had led to different responses of the dominant species in early and late successional stages. During the development of vegetation succession, community composition became simpler, and species diversity decreased significantly, which was a type of regressive succession. Therefore, measures should be adopted to manage these degraded, abandoned croplands.


Asunto(s)
Conservación de los Recursos Naturales , Suelo , China , Suelo/química , Ecosistema , Productos Agrícolas/crecimiento & desarrollo , Biodiversidad
3.
Artículo en Inglés | MEDLINE | ID: mdl-39049607

RESUMEN

BACKGROUND: There are conflicting reports on the factors that increase the likelihood of postpartum urinary retention (PUR). OBJECTIVES: We completed an updated systematic review and meta-analysis to identify the risk factors for PUR. SEARCH STRATEGY: An exhaustive search of the literature was undertaken using multiple databases, including PubMed, Web of Science, the Cochrane Library, and Embase to identify pertinent studies published up until November 4, 2023. SELECTION CRITERIA: Observational studies that provided outcomes to calculate the risk factors for PUR were included. DATA COLLECTION AND ANALYSIS: Two investigators separately performed the extraction of pertinent data from the articles. The risk factors for PUR were identified by pooling adjusted and unadjusted odds ratios (ORs) and 95% confidence intervals (CIs). Heterogeneity test, sensitivity analysis, and publication bias assessment were performed. MAIN RESULTS: This meta-analysis included 21 studies with a total of 36 951 participants. Meta-analysis was performed for 14 risk factors, and eight of these were statistically significant. The risk factors that were identified in this review included instrumental delivery (OR, 2.96 [95% CI, 1.82-4.80]; 95% prediction interval [PI], 0.67-12.98), relatively long duration of labor (OR, 1.04 [95% CI, 1.02-1.06]; 95% PI, 1.00-1.08), episiotomy (OR, 1.56 [95% CI, 1.19-2.06] 95% PI, 0.64-3.83), nulliparity (OR, 1.55 [95% CI, 1.30-1.84]; 95% PI, 0.94-2.77), epidural analgesia (OR, 2.99 [95% CI, 1.78-5.03]; 95% PI, 0.53-16.76), labor augmentation (OR, 2.21 [95% CI, 1.49-3.28]; 95% PI, 0.12-39.26), labor induction (OR, 1.73 [95% CI, 1.12-2.66]; 95% PI, 0.40-7.39), and perineal injury (OR, 2.75 [95% CI, 1.95-3.89]; 95% PI, 1.10-6.92). CONCLUSION: Instrumental delivery, extended labor duration, episiotomy, nulliparity, epidural analgesia, labor augmentation/induction, and perineal injury are significant risk factors for PUR. The findings could help physicians identify patients at risk in the postpartum setting.

4.
Clin Cancer Res ; 30(17): 3919-3936, 2024 Sep 03.
Artículo en Inglés | MEDLINE | ID: mdl-38900040

RESUMEN

PURPOSE: In multiple myeloma (MM), therapy-induced clonal evolution is associated with treatment resistance and is one of the most important hindrances toward a cure for MM. To further understand the molecular mechanisms controlling the clonal evolution of MM, we applied single-cell RNA sequencing (scRNA-seq) to paired diagnostic and posttreatment bone marrow (BM) samples. EXPERIMENTAL DESIGN: scRNA-seq was performed on 38 BM samples from patients with monoclonal gammopathy of undetermined significance (n = 1), MM patients at diagnosis (n = 19), MM posttreatment (n = 17), and one healthy donor (HD). The single-cell transcriptome data of malignant plasma cells (PC) and the surrounding immune microenvironment were analyzed. RESULTS: Profiling by scRNA-seq data revealed three primary trajectories of transcriptional evolution after treatment: clonal elimination in patients with undetectable minimal residual disease (MRD-) and clonal stabilization and clonal selection in detectable MRD (MRD+) patients. We noted a metabolic shift toward fatty acid oxidation in cycling-resistant PCs, whereas selective PCs favored the NF-κB pathway. Intriguingly, when comparing the genetic and transcriptional dynamics, we found a significant correlation between genetic and nongenetic factors in driving the clonal evolution. Furthermore, we identified variations in cellular interactions between malignant PCs and the tumor microenvironment. Selective PCs showed the most robust cellular interactions with the tumor microenvironment. CONCLUSIONS: These data suggest that MM cells could rapidly adapt to induction treatment through transcriptional adaptation, metabolic adaptation, and specialized immune evasion. Targeting therapy-induced resistance mechanisms may help to avert refractory disease in MM.


Asunto(s)
Evolución Clonal , Resistencia a Antineoplásicos , Mieloma Múltiple , Neoplasia Residual , Análisis de la Célula Individual , Microambiente Tumoral , Humanos , Mieloma Múltiple/genética , Mieloma Múltiple/patología , Mieloma Múltiple/tratamiento farmacológico , Análisis de la Célula Individual/métodos , Evolución Clonal/genética , Neoplasia Residual/genética , Neoplasia Residual/patología , Microambiente Tumoral/inmunología , Microambiente Tumoral/genética , Resistencia a Antineoplásicos/genética , Femenino , Masculino , Persona de Mediana Edad , Transcriptoma , Anciano , Perfilación de la Expresión Génica , Regulación Neoplásica de la Expresión Génica , Células Plasmáticas/patología , Células Plasmáticas/metabolismo , Células Plasmáticas/inmunología , Médula Ósea/patología
6.
Leukemia ; 38(6): 1299-1306, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38609496

RESUMEN

Growing evidence suggests that gain or amplification [gain/amp(1q)] accumulates during disease progression of multiple myeloma (MM). Previous investigations have indicated that small gain/amp(1q) subclones present at the time of diagnosis may evolve into dominant clones upon MM relapse. However, the influence of a minor clone of gain/amp(1q) on MM survival, as well as the correlation between different clonal sizes of gain/amp(1q) and the chromosomal instability (CIN) of MM, remains poorly understood. In this study, we analyzed fluorescence in situ hybridization (FISH) results of 998 newly diagnosed MM (NDMM) patients. 513 patients were detected with gain/amp(1q) at diagnosis. Among these 513 patients, 55 had a minor clone (≤20%) of gain/amp(1q). Patients with a minor clone of gain/amp(1q) displayed similar survival outcomes compared to those without gain/amp(1q). Further analysis demonstrated patients with a minor clone of gain/amp(1q) exhibited a clonal architecture similar to those without gain/amp(1q). Lastly, our results showed a significant increase in the clonal size of the minor clone of gain/amp(1q), frequently observed in MM. These findings suggested that a minor clone of gain/amp(1q) might represent an earlier stage in the pathogenesis of gain/amp(1q) and propose a "two-step" process in the clonal size changes of gain/amp(1q) in MM.


Asunto(s)
Hibridación Fluorescente in Situ , Mieloma Múltiple , Humanos , Mieloma Múltiple/genética , Mieloma Múltiple/patología , Mieloma Múltiple/mortalidad , Hibridación Fluorescente in Situ/métodos , Masculino , Femenino , Persona de Mediana Edad , Anciano , Pronóstico , Cromosomas Humanos Par 1/genética , Adulto , Evolución Clonal/genética , Anciano de 80 o más Años , Inestabilidad Cromosómica , Aberraciones Cromosómicas , Progresión de la Enfermedad
7.
J Immunother Cancer ; 12(4)2024 04 16.
Artículo en Inglés | MEDLINE | ID: mdl-38631712

RESUMEN

BACKGROUND: Approximately two-thirds of patients with relapsed or refractory large B-cell lymphoma (R/R LBCL) do not respond to or relapse after anti-CD19 chimeric antigen receptor T (CAR T)-cell therapy, leading to poor outcomes. Previous studies have suggested that intensified lymphodepletion and hematological stem cell infusion can promote adoptively transferred T-cell expansion, enhancing antitumor effects. Therefore, we conducted a phase I/II clinical trial in which CNCT19 (an anti-CD19 CAR T-cell) was administered after myeloablative high-dose chemotherapy and autologous stem cell transplantation (HDT/ASCT) in patients with R/R LBCL. METHODS: Transplant-eligible patients with LBCL who were refractory to first-line immunochemotherapy or experiencing R/R status after salvage chemotherapy were enrolled. The study aimed to evaluate the safety and efficacy of this combinational therapy. Additionally, frozen peripheral blood mononuclear cell samples from this trial and CNCT19 monotherapy studies for R/R LBCL were used to evaluate the impact of the combination therapy on the in vivo behavior of CNCT19 cells. RESULTS: A total of 25 patients with R/R LBCL were enrolled in this study. The overall response and complete response rates were 92.0% and 72.0%, respectively. The 2-year progression-free survival rate was 62.3%, and the overall survival was 68.5% after a median follow-up of 27.0 months. No unexpected toxicities were observed. All cases of cytokine release syndrome were of low grade. Two cases (8%) experienced grade 3 or higher CAR T-cell-related encephalopathy syndrome. The comparison of CNCT19 in vivo behavior showed that patients in the combinational therapy group exhibited enhanced in vivo expansion of CNCT19 cells and reduced long-term exhaustion formation, as opposed to those receiving CNCT19 monotherapy. CONCLUSIONS: The combinational therapy of HDT/ASCT and CNCT19 demonstrates impressive efficacy, improved CNCT19 behavior, and a favorable safety profile. TRIAL REGISTRATION NUMBERS: ChiCTR1900025419 and NCT04690192.


Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Linfoma de Células B Grandes Difuso , Humanos , Leucocitos Mononucleares , Recurrencia Local de Neoplasia/terapia , Trasplante Autólogo , Linfoma de Células B Grandes Difuso/terapia , Resultado del Tratamiento , Linfocitos T
8.
J Immunother Cancer ; 12(3)2024 Mar 04.
Artículo en Inglés | MEDLINE | ID: mdl-38443094

RESUMEN

BACKGROUND: Over 50% of patients with relapsed or refractory large B-cell lymphoma (r/r LBCL) receiving CD19-targeted chimeric antigen receptor (CAR19) T-cell therapy fail to achieve durable remission. Early identification of relapse or progression remains a significant challenge. In this study, we prospectively investigate the prognostic value of dynamic circulating tumor DNA (ctDNA) and track genetic evolution non-invasively, for the first time in an Asian population of r/r patients undergoing CAR19 T-cell therapy. METHODS: Longitudinal plasma samples were prospectively collected both before lymphodepletion and at multiple timepoints after CAR19 T-cell infusion. ctDNA was detected using a capture-based next-generation sequencing which has been validated in untreated LBCL. RESULTS: The study enrolled 23 patients with r/r LBCL and collected a total of 101 ctDNA samples. Higher pretreatment ctDNA levels were associated with inferior progression-free survival (PFS) (p=0.031) and overall survival (OS) (p=0.023). Patients with undetectable ctDNA negative (ctDNA-) at day 14 (D14) achieved an impressive 3-month complete response rate of 77.8% vs 22.2% (p=0.015) in patients with detectable ctDNA positive (ctDNA+), similar results observed for D28. CtDNA- at D28 predicted significantly longer 1-year PFS (90.9% vs 27.3%; p=0.004) and OS (90.9% vs 49.1%; p=0.003) compared with patients who remained ctDNA+. Notably, it is the first time to report that shorter ctDNA fragments (<170 base pairs) were significantly associated with poorer PFS (p=0.031 for D14; p=0.002 for D28) and OS (p=0.013 for D14; p=0.008 for D28) in patients with LBCL receiving CAR T-cell therapy. Multiple mutated genes exhibited an elevated prevalence among patients with progressive disease, including TP53, IGLL5, PIM1, BTG1, CD79B, GNA13, and P2RY8. Notably, we observed a significant correlation between IGLL5 mutation and inferior PFS (p=0.008) and OS (p=0.014). CONCLUSIONS: Our study highlights that dynamic ctDNA monitoring during CAR T-cell therapy can be a promising non-invasive method for early predicting treatment response and survival outcomes. Additionally, the ctDNA mutational profile provides novel insights into the mechanisms of tumor-intrinsic resistance to CAR19 T-cell therapy.


Asunto(s)
ADN Tumoral Circulante , Linfoma de Células B Grandes Difuso , Humanos , ADN Tumoral Circulante/genética , Inmunoterapia Adoptiva , Recurrencia Local de Neoplasia/genética , Recurrencia Local de Neoplasia/terapia , Genómica , Linfoma de Células B Grandes Difuso/genética , Linfoma de Células B Grandes Difuso/terapia
9.
Cancer Med ; 13(2): e6965, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38348996

RESUMEN

BACKGROUND: High-dose chemotherapy followed by autologous stem cell transplantation (ASCT) remains an effective treatment for non-Hodgkin lymphoma (NHL). The limited availability of carmustine has prompted the exploration of novel alternative conditioning regimens. This study aimed to compare the efficacy and safety profile of GBM/GBC (gemcitabine, busulfan, and melphalan or cyclophosphamide) conditioning compared with the standard BEAM/BEAC regimens (carmustine, etoposide, cytarabine, and melphalan or cyclophosphamide) for ASCT in patients with NHL. METHODS: A retrospective analysis was conducted on 231 NHL patients, who underwent ASCT from October 2010 to October 2021 at the Institute of Hematology & Blood Disease Hospital, including both first-line and salvage settings. This resulted in the inclusion of 112 patients in the GBM/GBC arm and 92 in the BEAM/BEAC arm. Propensity score matching was employed to validate the results. RESULTS: Disease subtype distribution was similar between the GBM/GBC and BEAM/BEAC groups, with diffuse large B-cell lymphoma being the most common (58.9% vs. 58.7%), followed by PTCL (17.0% vs. 18.5%) and MCL (14.3% vs. 14.1%). At 3 months post-ASCT, complete response (CR) rates were comparable (GBM/GBC 93.5% vs. BEAM/BEAC 91.1%; p = 0.607). The 4-year progression-free survival (78.4% vs. 82.3%; p = 0.455) and 4-year overall survival (88.1% vs. 87.7%; p = 0.575) were also similar. Both groups exhibited low non-relapse mortality at 4 years (GBM/GBC 1.8% vs. BEAM/BEAC 3.5%; p = 0.790) with no transplant-related mortalities reported. The GBM/GBC cohort demonstrated a higher incidence of grade 3/4 oral mucositis and hepatic toxicity, whereas the BEAM/BEAC group had more frequent cases of bacteremia or sepsis (13 cases vs. 5 in GBM/GBC). CONCLUSIONS: The GBM/GBC regimen is effective and well-tolerated, offering outcomes that are highly comparable to those in NHL patients conditioned with BEAM/BEAC, as demonstrated in a prognostically matched cohort.


Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Linfoma no Hodgkin , Humanos , Carmustina/efectos adversos , Gemcitabina , Trasplante de Células Madre Hematopoyéticas/métodos , Melfalán/efectos adversos , Estudios Retrospectivos , Trasplante Autólogo/métodos , Linfoma no Hodgkin/tratamiento farmacológico , Ciclofosfamida/uso terapéutico , Etopósido/efectos adversos , Citarabina/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Acondicionamiento Pretrasplante/métodos
11.
Am J Hematol ; 99(4): 523-533, 2024 04.
Artículo en Inglés | MEDLINE | ID: mdl-38247315

RESUMEN

Current standard predictive models of disease risk do not adequately account for the heterogeneity of survival outcomes in patients with new-diagnosed multiple myeloma (NDMM). In this retrospective, multicohort study, we collected clinical and genetic data from 1792 NDMM patients and identified the prognostic impact of all features. Using the top-ranked predictive features, a weighted Myeloma Prognostic Score System (MPSS) risk model was formulated and validated to predict overall survival (OS). In the training cohort, elevated lactate dehydrogenase level (LDH), International Staging System (ISS) Stage III, thrombocytopenia, and cumulative high-risk cytogenetic aberration (HRA) numbers were found to have independent prognostic significance. Each risk factor was defined as its weighted value respectively according to their hazard ratio for OS (thrombocytopenia 2, elevated LDH 1, ISS III 2, one HRA 1, and ≥2 HRA 2, points). Patients were further stratified into four risk groups: MPSS I (22.5%, 0 points), II (17.6%, 1 points), III (38.6%, 2-3 points), and IV (21.3%, 4-7 points). MPSS risk stratification showed optimal discrimination, as well as calibration, of four risk groups with median OS of 91.0, 69.8, 45.0, and 28.0 months, for patients in MPSS I to IV groups (p < .001), respectively. Importantly, the MPSS model retained its prognostic value in the internal validation cohort and an independent external validation cohort, and exhibited significant risk distribution compared with conventional prognostic models (R-ISS, R2-ISS, and MASS). Utilization of the MPSS model in clinical practice could improve risk estimation in NDMM patients, thus prompting individualized treatment strategies.


Asunto(s)
Mieloma Múltiple , Humanos , Pronóstico , Mieloma Múltiple/diagnóstico , Mieloma Múltiple/genética , Mieloma Múltiple/patología , Estadificación de Neoplasias , Estudios Retrospectivos , Modelos de Riesgos Proporcionales
12.
Blood Sci ; 6(1): e00179, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38239572

RESUMEN

Waldenstrom macroglobulinemia (WM) is a type of incurable, indolent B-cell lymphoma that is prone to relapse. Over time, treatment strategies have progressed from cytotoxic drugs to rituximab (R)- or bortezomib (V)-based regimens, and have now entered into an era of Bruton tyrosine kinase inhibitor (BTKi)-based regimens. However, the optimal treatment for the relapsed patients is still unclear. Herein, we analyzed the outcomes of the first- and second-line therapies in 377 patients with WM to illustrate the optimal choices for second-line therapy. After a median follow-up of 45.4 months, 89 patients received second-line therapy, and 53 patients were evaluated for response. The major response rates (MRR) of first- and second-line treatment were 65.1% and 67.9% (P = 0.678). The median progression-free survival (PFS) for the second-line therapy (PFS2) was shorter than that for the first-line therapy (PFS1) (56.3 vs 40.7 months, P = 0.03). However, PFS2 in targeted drugs group (R-/V-/BTKi-based regimens) was comparable to PFS1 (60.7 months vs 44.7 months, respectively, P = 0.21). Regarding second-line therapy, patients who underwent sequential treatment escalation-such as transitioning from cytotoxic drugs to R-/V-/BTKi-based regimens or from R-/V-based to BTKi-based regimens (escalation group) -had higher MRR (80.6% vs 47.1%, respectively, P = 0.023) and longer PFS2 (50.4 vs 23.5 months, respectively, P < 0.001) compared to the non-escalation group. Patients in the escalation group also had longer post-relapse overall survival compared with the non-escalation group (median, 50.4 vs 23.5 months, respectively, P = 0.039). Our findings indicate that sequential treatment escalation may improve the survival of patients with WM.

13.
Clin Cancer Res ; 30(6): 1131-1142, 2024 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-38170583

RESUMEN

PURPOSE: We investigated both the clinical utilities and the prognostic impacts of the clonotypic peptide mass spectrometry (MS)-EasyM, a blood-based minimal residual disease (MRD) monitoring protocol in multiple myeloma. EXPERIMENTAL DESIGN: A total of 447 sequential serum samples from 56 patients with multiple myeloma were analyzed using EasyM. Patient-specific M-protein peptides were sequenced from diagnostic samples; sequential samples were quantified by EasyM to monitor the M-protein. The performance of EasyM was compared with serum immunofixation electrophoresis (IFE), bone marrow multiparameter flow cytometry (MFC), and next-generation flow cytometry (NGF) detection. The optimal balance of EasyM sensitivity/specificity versus NGF (10-5 sensitivity) was determined and the prognostic impact of MS-MRD status was investigated. RESULTS: Of the 447 serum samples detected and measured by EasyM, 397, 126, and 92 had time-matching results for comparison with serum IFE, MFC-MRD, and NGF-MRD, respectively. Using a dotp >0.9 as the MS-MRD positive, sensitivity was 99.6% versus IFE and 100.0% versus MFC and NGF. Using an MS negative cutoff informed by ROC analysis (<1.86% of that at diagnosis), EasyM sensitivity remained high versus IFE (88.3%), MFC (85.1%), and NGF (93.2%), whereas specificity increased to 90.4%, 55.8%, and 93.2%, respectively. In the multivariate analysis, older diagnostic age was an independent predictor for progression-free survival [PFS; high risk (HR), 3.15; 1.26-7.86], the best MS-MRD status (MS-MRD negative) was independent predictor for both PFS (HR, 0.25; 0.12-0.52) and overall survival (HR, 0.16; 0.06-0.40). CONCLUSIONS: EasyM is a highly sensitive and minimal invasive method of MRD monitoring in multiple myeloma; MS-MRD had significant predictive ability for survival outcomes.


Asunto(s)
Mieloma Múltiple , Humanos , Neoplasia Residual/diagnóstico , Pronóstico , Sensibilidad y Especificidad , Citometría de Flujo/métodos
16.
Adv Ther ; 41(2): 672-685, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38079089

RESUMEN

INTRODUCTION: Waldenström's macroglobulinemia (WM) is a rare malignant B cell lymphoma which occurs in around 1-2% of all hematologic tumors. Ibrutinib was approved in China for WM on the basis of two global pivotal studies which enrolled no Chinese patients. The aim of this study was to determine the efficacy, safety, and pharmacokinetics of ibrutinib in Chinese patients with relapsed or refractory (r/r) WM. METHODS: This was an open-label, single-arm, multicenter phase 4 study conducted across five sites in China. Enrolled patients with clinicopathological confirmed WM received ibrutinib 420 mg once daily orally until disease progression or unacceptable toxicity. The primary endpoint was major response rate (MRR, partial response [PR], or better) according to the modified consensus criteria from the Sixth International Workshop on WM. RESULTS: Seventeen patients were enrolled; at data cutoff (March 19, 2022), MRR was 64.7% (90% confidence interval [CI] 42.0-83.4) and overall response rate was 100% (90% CI 83.8-100.0). One (5.9%) patient achieved very good PR, 10 (58.8%) achieved PR, and six (35.3%) achieved minor response. The median duration of response (PR or better) was 14.8 months (95% CI 10.8-not estimable [NE]). Median progression-free survival was 18.4 months (95% CI 12.9-NE). All patients experienced at least one treatment-emergent adverse event (TEAE) related to the study drug, and grade ≥ 3 TEAEs were reported in 13 (76.5%) patients. There were no TEAEs leading to dose reduction or death. The median model estimated maximum plasma concentration and area under the plasma concentration-time curve during 24 h after dosing at steady state were 40.5 ng/mL and 204 ng·h/mL, respectively. CONCLUSIONS: Ibrutinib demonstrated durable responses in Chinese patients with r/r WM. Treatment was well tolerated with no new safety signals compared with the pivotal global studies. Ibrutinib exposure was also comparable between Chinese and non-Chinese patients. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT04042376.


Asunto(s)
Linfoma de Células B , Macroglobulinemia de Waldenström , Humanos , Macroglobulinemia de Waldenström/tratamiento farmacológico , Piperidinas/uso terapéutico , Adenina/uso terapéutico
17.
Haematologica ; 109(2): 591-603, 2024 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-37534514

RESUMEN

The deletion of chromosome 17p (del(17p)) is considered a crucial prognostic factor at the time of diagnosis in patients with multiple myeloma (MM). However, the impact of del(17p) on survival at different clonal sizes at relapse, as well as the patterns of clonal evolution between diagnosis and relapse and their prognostic value, has not been well described. To address these issues, we analyzed the interphase fluorescence in situ hybridization (iFISH) results of 995 newly diagnosed MM (NDMM) patients and 293 patients with MM at their first relapse. Among these patients, 197 had paired iFISH data at diagnosis and first relapse. Our analysis of paired iFISH revealed that a minor clone of del(17p) at relapse but not at diagnosis was associated with poor prognosis in MM (hazard ratio for median overall survival 1.64 vs. 1.44). Fifty-six and 12 patients developed one or more new cytogenetic abnormalities at relapse, mainly del(17p) and gain/amp(1q), respectively. We classified the patients into six groups based on the change patterns in the clonal size of del(17p) between the two time points. Patients who did not have del(17p) during follow-up showed the best outcomes, whereas those who acquired del(17p) during their disease course, experienced compromised survival (median overall survival: 61.3 vs. 49.4 months; hazard ratio =1.64; 95% confidence interval: 1.06-2.56; P<0.05). In conclusion, our data confirmed the adverse impact of a minor clone of del(17p) at relapse and highlighted the importance of designing optimal therapeutic strategies to eliminate high-risk cytogenetic abnormalities (clinicaltrials gov. identifier: NCT04645199).


Asunto(s)
Mieloma Múltiple , Humanos , Aberraciones Cromosómicas , Hibridación Fluorescente in Situ , Mieloma Múltiple/terapia , Mieloma Múltiple/tratamiento farmacológico , Recurrencia Local de Neoplasia , Pronóstico
19.
Animals (Basel) ; 13(19)2023 Sep 29.
Artículo en Inglés | MEDLINE | ID: mdl-37835675

RESUMEN

Grazing management is one of the most widely practiced land uses globally. Quantifying the spatiotemporal distribution of livestock is critical for effective management of livestock-grassland grazing ecosystem. However, to date, there are few convincing solutions for livestock dynamic monitor and key parameters quantification under actual grazing situations. In this study, we proposed a pragmatic method for quantifying the grazing density (GD) and herding proximities (HP) based on unmanned aerial vehicles (UAVs). We further tested its feasibility at three typical household pastures on the Qinghai-Tibetan Plateau, China. We found that: (1) yak herds grazing followed a rotational grazing pattern spontaneously within the pastures, (2) Dispersion Index of yak herds varied as an M-shaped curve within one day, and it was the lowest in July and August, and (3) the average distance between the yak herd and the campsites in the cold season was significantly shorter than that in the warm season. In this study, we developed a method to characterize the dynamic GD and HP of yak herds precisely and effectively. This method is ideal for studying animal behavior and determining the correlation between the distribution of pastoral livestock and resource usability, delivering critical information for the development of grassland ecosystem and the implementation of sustainable grassland management.

20.
Front Plant Sci ; 14: 1150859, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37799559

RESUMEN

Grassland health assessment (GHA) is a bridge of study and management of grassland ecosystem. However, there is no standardized quantitative indicators and long-term monitor methods for GHA at a large scale, which may hinder theoretical study and practical application of GHA. In this study, along with previous concept and practices (i.e., CVOR, the integrated indexes of condition, vigor, organization and resilience), we proposed an assessment system based on the indicators monitored by unmanned aerial vehicles (UAVs)-UAVCVOR, and tested the feasibility of UAVCVOR at typical household pastures on the Qinghai-Tibetan Plateau, China. Our findings show that: (1) the key indicators of GHA could be measured directly or represented by the relative counterpart indicators that monitored by UAVs, (2) there was a significantly linear relationship between CVOR estimated by field- and UAV-based data, and (3) the CVOR decreased along with the increasing grazing intensity nonlinearly, and there are similar tendencies of CVOR that estimated by the two methods. These findings suggest that UAVs is suitable for GHA efficiently and correctly, which will be useful for the protection and sustainable management of grasslands.

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