RÉSUMÉ
In recent years, there have been limited reports on the efficacy of later-line anti-programmed cell death -1 (PD-1) therapy in achieving prolonged and complete remission in patients with hepatocellular carcinoma (HCC). Tislelizumab, a humanized anti-PD-1 monoclonal IgG4 antibody, has shown promising results in the treatment of HCC. This report highlights the case of a patient with HCC who experienced the development of lung metastatic lesions following HCC resection and chemotherapy, but achieved a prolonged complete response (CR) after receiving tislelizumab treatment. In April 2017, a 56-year-old male diagnosed with primary HCC underwent hepatectomy and hepatic arterial infusion pump placement. Following the surgery, the patient received adjuvant hepatic arterial infusion chemotherapy (HAIC) with 4 cycles of cisplatin+5-fluorouracil (PF) regimen starting in June 2017. In May 2018, lung metastatic lesions were detected, and the patient underwent 4 cycles of oxaliplatin+leucovorin+5-fluorouracil (FOLFOX) chemotherapy. However, the disease progressed in August 2018, leading to the administration of arsenic trioxide treatment. Despite this, further progression was observed in October 2018, prompting the patient's enrollment in a clinical trial for tislelizumab therapy. Initially, the patient achieved a partial response (PR) to tislelizumab, which was followed by a CR that lasted for almost 4 years. Unfortunately, tislelizumab treatment had to be discontinued due to immune-related adverse events (AE). Subsequently, the patient received lenvatinib and maintained a CR until July 2023. Tislelizumab monotherapy, when used as a third-line treatment, has demonstrated remarkable efficacy in facilitating patients with advanced HCC to attain a durable CR.
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The aim of the present study was to develop and evaluate a clinical-imaging-radiomic nomogram based on pre-enhanced computed tomography (CT) for pre-operative differentiation lipid-poor adenomas (LPAs) from metastases in patients with lung cancer with small hyperattenuating adrenal incidentalomas (AIs). A total of 196 consecutive patients with lung cancer, who underwent initial chest or abdominal pre-enhanced CT scan with small hyperattenuating AIs, were included. The patients were randomly divided into a training cohort with 71 cases of LPAs and 66 cases of metastases, and a testing cohort with 31 cases of LPAs and 28 cases of metastases. Plain CT radiological and clinical features were evaluated, including sex, age, size, pre-enhanced CT value (CTpre), shape, homogeneity and border. A total of 1,316 radiomic features were extracted from the plain CT images of the AIs, and the significant features selected by the least absolute shrinkage and selection operator were used to establish a Radscore. Subsequently, a clinical-imaging-radiomic model was developed by multivariable logistic regression incorporating the Radscore with significant clinical and imaging features. This model was then presented as a nomogram. The performance of the nomogram was assessed by calibration curves and decision curve analysis (DCA). A total of 4 significant radiomic features were incorporated in the Radscore, which yielded notable area under the receiver operating characteristic curves (AUCs) of 0.920 in the training dataset and 0.888 in the testing dataset. The clinical-imaging-radiomic nomogram incorporating the Radscore, CTpre, sex and age revealed favourable differential diagnostic performance (AUC: Training, 0.968; testing, 0.915) and favourable calibration curves. The nomogram was revealed to be more useful than the Radscore and the clinical-imaging model in clinical practice by DCA. The clinical-imaging-radiomics nomogram based on initial plain CT images by integrating the Radscore and clinical-imaging factors provided a potential tool to effectively differentiate LPAs from metastases in patients with lung cancer with small hyperattenuating AIs.
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Anti-PD-1 antibodies are a favorable treatment for relapsed or refractory extranodal natural killer T cell lymphoma (RR-ENKTL), however, the complete response (CR) rate and the duration of response (DOR) need to be improved. This phase 1b/2 study investigated the safety and efficacy of sintilimab, a fully human anti-PD-1 antibody, plus chidamide, an oral subtype-selective histone deacetylase inhibitor in 38 patients with RR-ENKTL. Expected objective response rate (ORR) of combination treatment was 80%. Patients received escalating doses of chidamide, administered concomitantly with fixed-dose sintilimab in 21-days cycles up to 12 months. No dose-limiting events were observed, RP2D of chidamide was 30 mg twice a week. Twenty-nine patients were enrolled in phase 2. In the intention-to-treat population (n = 37), overall response rate was 59.5% with a complete remission rate of 48.6%. The median DOR, progression-free survival (PFS), and overall survival (OS) were 25.3, 23.2, and 32.9 months, respectively. The most common grade 3 or higher treatment-emergent adverse events (AEs) were neutropenia (28.9%) and thrombocytopenia (10.5%), immune-related AEs were reported in 18 (47.3%) patients. Exploratory biomarker assessment suggested that a combination of dynamic plasma ctDNA and EBV-DNA played a vital prognostic role. STAT3 mutation shows an unfavorable prognosis. Although outcome of anticipate ORR was not achieved, sintilimab plus chidamide was shown to have a manageable safety profile and yielded encouraging CR rate and DOR in RR-ENKTL for the first time. It is a promising therapeutic option for this population.
Sujet(s)
Aminopyridines , Anticorps monoclonaux humanisés , Protocoles de polychimiothérapie antinéoplasique , Benzamides , Inhibiteurs de désacétylase d'histone , Lymphome T-NK extraganglionnaire , Humains , Mâle , Femelle , Adulte d'âge moyen , Benzamides/administration et posologie , Benzamides/usage thérapeutique , Benzamides/effets indésirables , Sujet âgé , Lymphome T-NK extraganglionnaire/traitement médicamenteux , Lymphome T-NK extraganglionnaire/anatomopathologie , Inhibiteurs de désacétylase d'histone/usage thérapeutique , Inhibiteurs de désacétylase d'histone/administration et posologie , Inhibiteurs de désacétylase d'histone/effets indésirables , Anticorps monoclonaux humanisés/usage thérapeutique , Anticorps monoclonaux humanisés/administration et posologie , Anticorps monoclonaux humanisés/effets indésirables , Adulte , Aminopyridines/administration et posologie , Aminopyridines/effets indésirables , Protocoles de polychimiothérapie antinéoplasique/usage thérapeutique , Protocoles de polychimiothérapie antinéoplasique/effets indésirables , Récepteur-1 de mort cellulaire programmée/antagonistes et inhibiteurs , Récepteur-1 de mort cellulaire programmée/immunologieRÉSUMÉ
This registration study assessed clinical outcomes of TQ-B3525, the dual phosphatidylinositol-3-kinase (PI3K) α/δ inhibitor, in relapsed and/or refractory follicular lymphoma (R/R FL). This phase II study (ClinicalTrials.gov NCT04324879. Registered March 27, 2020) comprised run-in stage and stage 2. R/R FL patients after ≥2 lines therapies received oral 20 mg TQ-B3525 once daily in a 28-day cycle until intolerable toxicity or disease progression. Primary endpoint was independent review committee (IRC)-assessed objective response rate (ORR). Based on results (ORR, 88.0%; duration of response [DOR], 11.8 months; progression-free survival [PFS], 12.0 months) in 25 patients at run-in stage, second stage study was initiated and included 82 patients for efficacy/safety analysis. Patients received prior-line (median, 3) therapies, with 56.1% refractory to previous last therapies; 73.2% experienced POD24 at baseline. At stage 2, ORR was 86.6% (71/82; 95% CI, 77.3-93.1%), with 28 (34.2%) complete responses. Disease control rate was 95.1% due to 7 (8.5%) stable diseases. Median time to response was 1.8 months. Among 71 responders, median DOR was not reached; 18-month DOR rate was 51.6%. with median follow-up of 13.3 months, median PFS was 18.5 (95% CI, 10.2-not estimable) months. Median overall survival (OS) was not reached by cutoff date; 24-month OS rate was estimated as 86.1%. Response rates and survival data were consistent across all subgroups. Grade 3 or higher treatment-related adverse events were observed in 63 (76.8%) cases, with neutropenia (22.0%), hyperglycemia (19.5%), and diarrhea (13.4%) being common. TQ-B3525 showed favorable efficacy and safety for R/R FL patients after ≥2 lines prior therapies.
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Lymphome folliculaire , Humains , Lymphome folliculaire/traitement médicamenteux , Lymphome folliculaire/génétique , Survie sans progression , Inhibiteurs des phosphoinositide-3 kinases/usage thérapeutiqueRÉSUMÉ
BACKGROUND: Studying the causes of death among deceased spouses and surviving partners may provide insights into the underlying mechanisms of the association between widowhood and mortality. This study investigated the mortality risk of widowhood in Taiwan, examined the association of the cause of death between widowed individuals and their deceased spouses and explored potential modifying effects by age, gender and duration after widowhood. METHODS: This matched cohort study utilized Taiwan's National Health Insurance claims database and National Death Registry. In total, 204â010 widowed men and 596â136 widowed women were identified with a mean follow-up period of 6.9 and 7.9 years, respectively, and 816â040 comparison men and 2â384â544 comparison women were selected. RESULTS: Widowhood was associated with an increased mortality risk, with widowed men having a 1.32 increased risk and widowed women having a 1.27 increased risk. Age at spousal death and duration modified the associations after widowhood. The widowed individuals are more likely to die by the same cause as the deceased spouse if they died by suicide, accident, endocrine, gastrointestinal disorders or infection. CONCLUSIONS: The study suggests that healthcare policies and interventions should be developed to improve widowed individuals' health and overall welfare.
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Suicide , Veuvage , Mâle , Humains , Femelle , Études de cohortes , Taïwan/épidémiologieRÉSUMÉ
Natural killer/T-cell lymphoma (NKTCL) is a highly heterogeneous disease with a poor prognosis. However, the genomic characteristics and proper treatment strategies for non-upper aerodigestive tract NKTCL (NUAT-NKTCL), a rare subtype of NKTCL, remain largely unexplored. In this study, 1589 patients newly diagnosed with NKTCL at 14 hospitals were assessed, 196 (12.3%) of whom had NUAT-NKTCL with adverse clinical characteristics and an inferior prognosis. By using whole-genome sequencing (WGS) and whole-exome sequencing (WES) data, we found strikingly different mutation profiles between upper aerodigestive tract (UAT)- and NUAT-NKTCL patients, with the latter group exhibiting significantly higher genomic instability. In the NUAT-NKTCL cohort, 128 patients received frontline P-GEMOX chemotherapy, 37 of whom also received anti-PD-1 immunotherapy. The application of anti-PD-1 significantly improved progression-free survival (3-year PFS rate 53.9% versus 17.0%, P = 0.009) and overall survival (3-year OS rate 63.7% versus 29.2%, P = 0.01) in the matched NUAT-NKTCL cohort. WES revealed frequent mutations involving immune regulation and genomic instability in immunochemotherapy responders. Our study showed distinct clinical characteristics and mutational profiles in NUAT-NKTCL compared with UAT patients and suggested adding anti-PD-1 immunotherapy in front-line treatment of NUAT-NKTCL. Further studies are needed to validate the efficacy and related biomarkers for immunochemotherapy proposed in this study.
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Lymphome T-NK extraganglionnaire , Humains , Lymphome T-NK extraganglionnaire/génétique , Lymphome T-NK extraganglionnaire/thérapie , Lymphome T-NK extraganglionnaire/diagnostic , Génomique , Immunothérapie , Instabilité du génome , Cellules tueuses naturelles/anatomopathologieRÉSUMÉ
Importance: The bioequivalence of denosumab biosimilar has yet to be studied in a 53-week, multicenter, large-scale, and head-to-head trial. A clinically effective biosimilar may help increase access to denosumab in patients with solid tumor-related bone metastases. Objectives: To establish the biosimilarity of MW032 to denosumab in patients with solid tumor-related bone metastases based on a large-scale head-to-head study. Design, Setting, and Participants: In this 53-week, randomized, double-blind, phase 3 equivalence trial, patients with solid tumors with bone metastasis were recruited from 46 clinical sites in China. Overall, 856 patients were screened and 708 eligible patients were randomly allocated to receive either MW032 or denosumab. Interventions: Patients were randomly assigned (1:1) to receive MW032 or reference denosumab subcutaneously every 4 weeks until week 49. Main Outcomes and Measures: The primary end point was percentage change from baseline to week 13 of natural logarithmic transformed urinary N-telopeptide/creatinine ratio (uNTx/uCr). Results: Among the 701 evaluable patients (350 in the MW032 group and 351 in the denosumab group), the mean (range) age was 56.1 (22.0-86.0) years and 460 patients were women (65.6%). The mean change of uNTx/uCr from baseline to week 13 was -72.0% (95% CI, -73.5% to -70.4%) in the MW032 group and -72.7% (95% CI, -74.2% to -71.2%) in the denosumab group. These percent changes corresponded to mean logarithmic ratios of -1.27 and -1.30, or a difference of 0.02. The 90% CI for the difference (-0.04 to 0.09) was within the equivalence margin (-0.13 to 0.13); the mean changes of uNTx/uCr and bone-specific alkaline phosphatase (s-BALP) at each time point were also similar during 53 weeks. The differences of uNTx/uCr change were 0.015 (95% CI, -0.06 to 0.09), -0.02 (95% CI, -0.09 to 0.06), -0.05 (95% CI, -0.13 to 0.03) and 0.001 (95% CI, -0.10 to 0.10) at weeks 5, 25, 37, and 53, respectively. The differences of s-BALP change were -0.006 (95% CI, 0.06 to 0.05), 0.00 (95% CI, -0.07 to 0.07), -0.085 (95% CI, -0.18 to 0.01), -0.09 (95% CI, -0.20 to 0.02), and -0.13 (95% CI, -0.27 to 0.004) at weeks 5, 13, 25, 37 and 53, respectively. No significant differences were observed in the incidence of skeletal-related events (-1.4%; 95% CI, -5.8% to 3.0%) or time to first on-study skeletal-related events (unadjusted HR, 0.86; P = .53; multiplicity adjusted HR, 0.87; P = .55) in the 2 groups. Conclusions and Relevance: MW032 and denosumab were biosimilar in efficacy, population pharmacokinetics, and safety profile. Availability of denosumab biosimilars may broaden the access to denosumab and reduce the drug burden for patients with advanced tumors. Trial Registration: ClinicalTrials.gov Identifier: NCT04812509.
Sujet(s)
Produits pharmaceutiques biosimilaires , Tumeurs osseuses , Humains , Femelle , Adulte d'âge moyen , Sujet âgé , Sujet âgé de 80 ans ou plus , Mâle , Dénosumab , Anticorps monoclonaux humanisés , Tumeurs osseuses/secondaire , Créatinine , Méthode en double aveugleRÉSUMÉ
BACKGROUND: Ovarian cancer (OVC) has emerged as a fatal gynecological malignancy as a result of a lack of reliable methods for early detection, limited biomarkers and few treatment options. Immune cell-related telomeric genes (ICRTGs) show promise as potential biomarkers. METHODS: ICRTGs were discovered using weighted gene co-expression network analysis (WGCNA). ICRTGs were screened for significant prognosis using one-way Cox regression analysis. Subsequently, molecular subtypes of prognosis-relevant ICRTGs were constructed and validated for OVC, and the immune microenvironment's landscape across subtypes was compared. OVC prognostic models were built and validated using prognosis-relevant ICRTGs. Additionally, chemotherapy susceptibility drugs for OVC patients in the low- and high-risk groups of ICRTGs were screened using genomics of drug susceptibility to cancer (GDSC). Finally, the immunotherapy response in the low- and high-risk groups was detected using the data from GSE78220. We conducted an immune index correlation analysis of ICRTGs with significant prognoses. The MAP3K4 gene, for which the prognostic correlation coefficient is the highest, was validated using tissue microarrays for a prognostic-immune index correlation. RESULTS: WGCNA analysis constructed a gene set of ICRTGs and screened 22 genes with prognostic significance. Unsupervised clustering analysis revealed the best molecular typing for two subtypes. The Gene Set Variation Analysis algorithm was used to calculate telomere scores and validate the molecular subtyping. A prognostic model was constructed using 17 ICRTGs. In the The Cancer Genome Atlas-OVC training set and the Gene Expression Omnibus validation set (GSE30161), the risk score model's predicted risk groups and the actual prognosis were shown to be significantly correlated. GDSC screened Axitinib, Bexarotene, Embelin and the GSE78220 datasets and demonstrated that ICRTGs effectively distinguished the group that responds to immunotherapy from the non-responsive group. Additionally, tissue microarray validation results revealed that MAP3K4 significantly predicted patient prognosis. Furthermore, MAP3K4 exhibited a positive association with PD-L1 and a negative relationship with the M1 macrophage markers CD86 and INOS. CONCLUSIONS: ICRTGs may be reliable biomarkers for the molecular typing of patients with OVC, enabling the prediction of prognosis and immunotherapy efficacy.
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Tumeurs de l'ovaire , Télomère , Humains , Femelle , Télomère/génétique , Tumeurs de l'ovaire/diagnostic , Tumeurs de l'ovaire/génétique , Tumeurs de l'ovaire/thérapie , Algorithmes , Axitinib , Marqueurs biologiques , Microenvironnement tumoral/génétiqueRÉSUMÉ
Repeated claims that a dwindling supply of potential caregivers is creating a crisis in care for the U.S. aging population have not been well-grounded in empirical research. Concerns about the supply of family care do not adequately recognize factors that may modify the availability and willingness of family and friends to provide care to older persons in need of assistance or the increasing heterogeneity of the older population. In this paper, we set forth a framework that places family caregiving in the context of older adults' care needs, the alternatives available to them, and the outcomes of that care. We focus on care networks, rather than individuals, and discuss the demographic and social changes that may alter the formation of care networks in the future. Last, we identify research areas to prioritize in order to better support planning efforts to care for the aging U.S. population.
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Vieillissement , Aidants , Humains , Sujet âgé , Sujet âgé de 80 ans ou plus , Recherche empirique , Démographie , FamilleRÉSUMÉ
In December 2022, the Omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) became dominant in China due to its high infectivity and lower mortality rate. The risk of critical illness and mortality among patients with hematologic malignancies who contracted SARS-CoV-2 was particularly high. The aim of this study was to draft a consensus to facilitate effective treatments for these patients based on the type and severity of the disease. Following the outbreak of the novel coronavirus in China, a steering committee consisting of experienced hematologists was formed by the Specialized Committee of Oncology and Microecology of the Chinese Anti-Cancer Association. The expert group drafted a consensus on the management and intervention measures for different types of hematologic malignancies based on the clinical characteristics of the Omicron variant of the SARS-CoV-2 infection, along with relevant guidelines and literature. The expert group drafted independent recommendations on several important aspects based on the epidemiology of the Omicron variant in China and the unique vulnerability of patients with hematologic malignancies. These included prophylactic vaccinations for those with hematologic malignancies, the use of plasma from blood donors who recovered from the novel coronavirus infection, the establishment of negative pressure wards, the use of steady-state mobilization of peripheral blood hematopoietic stem cells, the provision of psychological support for patients and medical staff, and a focus on maintaining a healthy intestinal microecology.
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COVID-19 , Tumeurs hématologiques , Humains , SARS-CoV-2 , Consensus , Tumeurs hématologiques/complications , Tumeurs hématologiques/thérapie , Chine/épidémiologieRÉSUMÉ
Aerobic glycolysis is critical for cancer progression and can be exploited in cancer therapy. Here, we report that the human carboxymethylenebutenolidase homolog (carboxymethylenebutenolidase-like [CMBL]) acts as a tumor suppressor by reprogramming glycolysis in colorectal cancer (CRC). The anti-cancer action of CMBL is mediated through its interactions with the E3 ubiquitin ligase TRIM25 and the glycolytic enzyme phosphofructokinase-1 platelet type (PFKP). Ectopic CMBL enhances TRIM25 binding to PFKP, leading to the ubiquitination and proteasomal degradation of PFKP. Interestingly, CMBL is transcriptionally activated by p53 in response to genotoxic stress, and p53 activation represses glycolysis by promoting PFKP degradation. Remarkably, CMBL deficiency, which impairs p53's ability to inhibit glycolysis, makes tumors more sensitive to a combination therapy involving the glycolysis inhibitor 2-deoxyglucose. Taken together, our study demonstrates that CMBL suppresses CRC growth by inhibiting glycolysis and suggests a potential combination strategy for the treatment of CMBL-deficient CRC.
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Tumeurs , Phosphofructokinase-1, type C , Humains , Lignée cellulaire tumorale , Glucose/métabolisme , Glycolyse , Phosphofructokinase-1/métabolisme , Phosphofructokinase-1, type C/métabolisme , Phosphofructokinases/métabolisme , Protéine p53 suppresseur de tumeur/métabolismeRÉSUMÉ
Sarcopenia is known to be associated with an increased risk of adverse outcomes in a variety of malignancies, but its impact in extranodal natural killer/T cell lymphoma, nasal type (ENKTL-NT) is unknown. The aim of this study was to explore the prognostic relevance of sarcopenia defined by MRI-based masticatory muscle index in ENKTL-NT patients. A total of 112 patients with newly diagnosed ENKTL-NT who underwent cranial magnetic resonance imaging (MRI) were enrolled. The masticatory skeletal muscle index (M-SMI) was measured based on T2-weighted MR images and sarcopenia was defined by M-SMI<5.5 cm2/ m2. The median M-SMI was 5.47 (4.91-5.96) cm2/m2; 58 were identified with sarcopenia in this cohort. On multivariate analyses, sarcopenia was the only independently risk factor predicting overall survival (HR, 4.590; 95% CI, 1.657-12.715; p = 0.003), progression-free survival (HR, 3.048; 95% CI, 1.515-6.130; p = 0.002), and treatment response (HR, 0.112; 95% CI, 0.042-0.301; p < 0.001). In addition, we found that integrating sarcopenia into prognostic indices could improve the discriminative power of the corresponding original model. Stratification analysis showed that sarcopenia was able to further identify survival differences in patients that could not be distinguished by prognostic models. In summary, our study suggests that sarcopenia defined by MRI-based M-SMI represents a new and routinely applicable prognostic indicator of clinical outcome or predictor of treatment response in ENKTL-NT patients, and may aid in risk stratification and treatment decisions.
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Lymphome T-NK extraganglionnaire , Sarcopénie , Humains , Pronostic , Lymphome T-NK extraganglionnaire/diagnostic , Sarcopénie/imagerie diagnostique , Sarcopénie/anatomopathologie , Muscles masticateurs/anatomopathologie , Cellules tueuses naturelles/anatomopathologie , Études rétrospectivesRÉSUMÉ
OBJECTIVES: Do adults without kin experience a care gap where they need help with activities of daily living but get no help from any source? We examine the prevalence of the care gap across Europe, and test whether those without partners or children substitute for their lack of close kin with help from broader networks, or whether they disproportionately experience care gaps. METHODS: Using data from the Survey on Health, Ageing and Retirement in Europe, we estimate the care gap in 28 European countries and Israel, how it varies, and who provides help for respondents with different family structures. RESULTS: The care gap is substantial, with 6.1% of all respondents ages 50 and above reporting a gap. It is highest in Western and Eastern Europe and lowest in Southern Europe and Israel. Respondents without partners or children are significantly more likely to have care gaps than those with close kin. However, respondents without close kin draw more often on more diverse networks of friends and relatives and use nursing home care. DISCUSSION: Our study introduces the concept of the care gap and shows that although it is most common among unpartnered adults without children it is also quite common for those with immediate family. A broader network partially but not completely substitutes for care gaps among those without immediate family. Our results offer new insights into the demand for public care services in countries with diverse welfare states.
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Activités de la vie quotidienne , Vieillissement , Humains , Europe/épidémiologie , Retraite , Europe de l'EstRÉSUMÉ
Rosa roxburghii f. eseiosa Ku is a variety of Rosa roxburghii, with two known genotypes: Wuci 1 and Wuci 2. The lack of prickle on the peel of R. roxburghii f. eseiosa makes it easy to pick and process, but its fruit size is small. Therefore, we aim to induce polyploidy in order to obtain a larger fruit variety of R. roxburghii f. eseiosa. In this study, current-year stems of Wuci 1 and Wuci 2 were used as materials for polyploid induction, which was carried out through colchicine treatment coupled with tissue culture and rapid propagation technology. Impregnation and smearing methods were effectively used to produce polyploids. Using flow cytometry and a chromosome counting method, it was found that one autotetraploid of Wuci 1 (2n = 4x = 28) was obtained by the impregnation method before primary culture, with a variation rate of 1.11%. Meanwhile, seven Wuci 2 bud mutation tetraploids (2n = 4x = 28) were produced by smearing methods during the training seedling stage. When tissue-culture seedlings were treated with 20 mg/L colchicine for 15 days, the highest polyploidy rate was up to 60%. Morphological differences between different ploidys were observed. The side leaflet shape index, guard cell length, and stomatal length of the Wuci 1 tetraploid were significantly different from those of the Wuci 1 diploid. The terminal leaflet width, terminal leaflet shape index, side leaflet length, side leaflet width, guard cell length, guard cell width, stomatal length, and stomatal width of the Wuci 2 tetraploid were significantly different from those of the Wuci 2 diploid. Additionally, the leaf color of the Wuci 1 and Wuci 2 tetraploids changed from light to dark, with an initial decrease in chlorophyll content followed by an increase. In summary, this study established an effective method for inducing polyploids in R. roxburghii f. eseiosa, which could provide a foundation for the breeding and development of new genetic resources for R. roxburghii f. eseiosa and other R. roxburghii varieties in the future.
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BACKGROUND: The prognosis of patients with angioimmunoblastic T cell lymphoma (AITL) remains dismal, with their 5-year overall survival (OS) and progression-free survival (PFS) rates of 32-41% and 18-38%, respectively. Spleen involvement occurs in a proportion of patients with AITL. But still, it is unclear whether spleen involvement impacts the prognosis of AITL patients. In this study, we aim to establish new prognostic indicators for the identification of high-risk patients to draft optimal treatment regimens. METHODS: We collected and counted the clinical data of 54 patients with AITL treated with CHOP-based first-line chemotherapy regimen between 2010 and 2021 at Hubei Cancer Hospital and Hunan Cancer Hospital. In addition, all patients received PET-CT scan prior to receiving treatment. We performed univariate and multivariate analyses to assess the predictive role of tumor characteristics, laboratory, and radiographic data for the prognosis of AITL. RESULTS: We observed that PFS and OS are worse in patients with high ECOG scores, spleen involvement, and low serum albumin levels in patients with AITL. In univariate analysis, stage (HR 3.515 [1.142-10.822], p = 0.028) and spleen involvement (HR 8.378 [1.085-64.696, p = 0.042) were correlated with PFS in patients with AITL. Besides, stage (HR 3.439 [1.108-10.674], p = 0.033) and spleen involvement (HR 11.002 [1.420-85.254], p = 0.022) were significantly correlated with OS. Consistently, spleen involvement was correlated with OS (HR 16.571 [1.350-203.446], p = 0.028) and PFS (HR 10.905 [1.037-114.690], p = 0.047) in AITL patients in a multivariate analysis. CONCLUSION: This study demonstrates that spleen involvement might be used as a prognostic indicator for AITL patients.
Sujet(s)
Lymphadénopathie angio-immunoblastique , Lymphome T , Humains , Rate/imagerie diagnostique , Tomographie par émission de positons couplée à la tomodensitométrie , Lymphadénopathie angio-immunoblastique/traitement médicamenteux , Pronostic , Lymphome T/traitement médicamenteux , Études rétrospectivesRÉSUMÉ
PURPOSE: To investigate the efficacy and safety of the novel orally active PI3Kδ inhibitor in relapsed and/or refractory patients with follicular lymphoma (FL) who had received at least two prior systemic treatments. PATIENTS AND METHODS: Histologically confirmed relapsed and/or refractory patients with FL with disease progression after receiving second-line or greater systemic therapy were enrolled. Linperlisib was administered at 80 mg every day, orally in a 28-day cycle until disease progression or intolerable toxicity occurred. The primary outcome for the study was the objective response rate (ORR), with secondary outcomes including the duration of response (DOR), progression-free survival (PFS), overall survival (OS), disease control rate, and drug safety profile. RESULTS: Of 114 screened relapsed and/or refractory patients with FL, 84 were enrolled in the full analysis set (FAS). The ORR of the 84 FAS patients was 79.8% [95% confidence interval (CI), 69.6-87.8, 67 patients], with 13 patients (15.5%) achieving a complete response and 54 patients (64.3%) with a partial response. The median DOR was 12.3 months (95% CI, 9.3-15.9). The median PFS was 13.4 months (95% CI, 11.1-16.7). The 12-month OS rate was 91.4% (95% CI, 82.7-95.8) and a median OS not reached by 42 months. The most frequent (>3%) treatment-related adverse events Grade ≥3 were infectious pneumonia (19.0%), neutropenia (15.5%), decreased lymphocyte count (4.8%), decreased leukocyte count (4.8%), increased lipase (3.6%), decreased platelet count (3.6%), hypertriglyceridemia (3.6%), and interstitial lung disease (3.6%). CONCLUSIONS: Linperlisib demonstrated compelling clinical activity and manageable tolerability for relapsed and/or refractory patients with FL who had received at least two prior systemic therapies.
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Lymphome folliculaire , Humains , Lymphome folliculaire/anatomopathologie , Inhibiteurs de l'angiogenèse/usage thérapeutique , Inhibiteurs de protéines kinases/effets indésirables , Protocoles de polychimiothérapie antinéoplasique/usage thérapeutique , Évolution de la maladie , Résultat thérapeutiqueRÉSUMÉ
BACKGROUND: This study aimed to better characterize the clinicopathologic characteristics, outcomes, and prognostic factors of AITL in China. METHODS: We retrospectively analyzed 312 patients with AITL enrolled between January 2011 and December 2020 from five institutions in China. RESULTS: The median age was 65 years, with 92.6% advanced stage, 59.7% elevated LDH, 46.1% anemia, and 44.0% hypergammaglobulinemia. The majority of patients (84.9%) received anthracycline-based regimens with or without etoposide, and only 6.1% underwent autologous stem cell transplantation following first remission. The 5-year OS and PFS estimates were 43.4% and 25.0% with no significant improvement of survival between patients treated during 2011-2015 and 2016-2020, respectively. Both the International Prognostic Index (IPI) and the prognostic index for PTCL, not otherwise specified (PIT), were predictive for OS. In multivariate analysis, age >70 years, elevated LDH, and albumin level <35 g/L were independent prognostic factors for OS. Combining these three factors, a novel prognostic model (the Chinese AITL score) was constructed, which stratified patients into low-, intermediate-, and high-risk groups, with 5-year OS rates of 69.0%, 41.5%, and 23.7%, respectively. This new model was successfully validated in an independent cohort. CONCLUSIONS: Patients with AITL were mainly treated with anthracycline-based regimens, and the outcomes were still unsatisfactory in China. Our novel prognostic model may improve our ability to identify patients at different risks for alternative therapies.
Sujet(s)
Transplantation de cellules souches hématopoïétiques , Lymphadénopathie angio-immunoblastique , Lymphome T périphérique , Humains , Sujet âgé , Pronostic , Études rétrospectives , Transplantation autologue , Lymphadénopathie angio-immunoblastique/thérapie , Anthracyclines/usage thérapeutiqueRÉSUMÉ
To investigate the imaging characteristics of sarcoidosis and Hodgkin's lymphoma based on mediastinal enlarged lymph node using spectral CT and evaluate whether the quantitative information can improve the differential diagnosis of these diseases. This retrospective study was approved by the institutional review board, and written informed consent was obtained from all patients. Overall, 21 patients with sarcoidosis and 39 patients with Hodgkin's lymphoma were examined with CT spectral imaging during the arterial phase (AP) and venous phase (VP). The CT values on 40 to 140 keV monochromatic images and iodine (water) concentrations of enlarged lymph nodes were obtained in AP and VP. Iodine concentrations (ICs) were normalized to the iodine concentration in the aorta. The differences in normalized iodine concentrations (NICs) and hounsfield units (HU) curve slop (λHU) were calculated. Anatomical distribution of mediastinal lymph nodes and morphologic features were also compared. Receiver operating characteristic curves were generated to help establish threshold values for the parameters required for the significant differentiation of sarcoidosis from lymphomas. The CT values on 40 to 100 keV monochromatic images in AP and 40 to 50 keV in VP were higher in sarcoidosis than those in Hodgkin's lymphoma, the differences were statistically significant (Pâ <â .05); NICs during the AP and λHU during the AP (VP) in patients with sarcoidosis differed significantly from those in patients with Hodgkin's lymphoma. Receiver operating characteristic curves analysis showed that the monochromatic CT value on 40 keV in AP had the highest sensitivity (71.4%) and specificity (100%) in differentiating sarcoidosis from Hodgkin's lymphoma. The anatomic distribution, coalescence, calcification, compression, enhancement pattern and enhancement degree of the mediastinal enlarged lymph node differed significantly between the groups (Pâ <â .05). The combination of monochromatic CT value, NICs and λHU had higher sensitivity and specificity than did those of conventional qualitative CT image analysis during the combined phases. CT spectral imaging has promising potential for the diagnostic differentiation of Hodgkin's lymphomas and sarcoidosis. The monochromatic CT value, iodine content and λHU could be valuable parameters for differentiating Hodgkin's lymphomas and sarcoidosis based on mediastinal enlarged lymph node.
Sujet(s)
Maladie de Hodgkin , Iode , Lymphadénopathie , Sarcoïdose , Humains , Maladie de Hodgkin/imagerie diagnostique , Diagnostic différentiel , Études rétrospectives , Noeuds lymphatiques/imagerie diagnostique , Sarcoïdose/imagerie diagnostique , TomodensitométrieRÉSUMÉ
There is an ongoing debate over whether living apart together (LAT) relationships are simply long-term relationships or alternatives to cohabitation or marriage. This study examined cohabitation and marriage expectations among older adults who LAT in the United States to address the debate. The analyses also compared the marriage expectations of older adults who LAT and cohabitors. Using data from the 2011 Wisconsin Longitudinal Study (WLS), we examined the union expectations of 250 individuals who LAT and 234 cohabitors. After providing a demographic portrait of older adults who LAT, we used ordered logistic regression models to predict their cohabitation and marriage expectations. Additional models predicted marriage expectations for older adults who LAT versus cohabitors. Older adults who LAT were unlikely to expect to formalize their unions. Adults who LAT were less likely to expect marriage than cohabitors. LAT relationships appear to be long-term partnerships in the United States.
RÉSUMÉ
Background: Immunotherapy has been shown to improve the overall survival (OS) in patients with advanced or metastatic non-small cell lung cancer (NSCLC) without driver gene mutations. However, monotherapy with immunotherapy alone or combined with chemotherapy in NSCLC patients with untreated brain metastases (BM) is still under debate. Data regarding treatment of BM with immunotherapy and temozolomide (TMZ) in patients with NSCLC is rare. Case Presentation: A 60-year-old male due to cough and expectoration presented in our hospital. Chest computed tomography (CT), brain magnetic resonance imaging (MRI) and immunohistochemistry of a mediastinal lymph node biopsy were administered, he was diagnosed with stage IIIB lung adenocarcinoma. Without driver gene mutations, he was treated with platinum-based chemotherapy because he refused to accept concurrent radiation therapy (RT). Heavy cough companied with hemoptysis and chest CT scan both revealed progressive disease (PD) after 6 cycles of chemotherapy. Immunotherapy was consequently considered, while two metastatic lesions in the brain were confirmed after combined treatment of pembrolizumab with docetaxel. TMZ was administered in combination with pembrolizumab (200 mg, day 1). A new metastasis in the right occipital lobe was detected on a scan 1 month later, though the other 2 lesions continued to shrink. The treatment was continued, MRI and CT scans suggested complete response (CR) was achieved for both the BM and lung lesions after 3 cycles. Consolidation therapy with TMZ and pembrolizumab (100 mg) per month was considered for another 7 months. Maintenance monotherapy with pembrolizumab (100 mg) was selected because of his stable CR status. At 59 months since diagnosis, the patient remains alive, with CR for both the primary lesions and BM. The patient experienced slight numbness on each side of his feet. There was no occurrence of adverse effects greater than grade 3. Conclusions: The data indicates that immunotherapy combined with TMZ for untreated BM in NSCLC patients maybe an efficient and safe decision making therapeutic choice. Despite the encouraging efficacy of the combination, it is an isolated case and the speculation of synergism need to be proved in further pharmacokinetic/pharmacodynamic studies even in large randomized controlled trials.