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Background Synchronous multiple primary malignant tumors (sMPMTs) are sometimes diagnosed in patients with malignant lymphoma. We herein investigated the prognostic impact of sMPMT in lymphoma patients and the optimal treatment strategy. Methods Seventy-five patients with sMPMTs (5.8%) among 1285 patients with lymphoma newly diagnosed between August 2004 and April 2020 were enrolled. Results In patients with indolent lymphoma, those with sMPMTs had a worse prognosis than those without sMPMTs (5-year overall survival [OS]: 73.4% and 87.8%, respectively; P = 0.047). Among those with high and low tumor burden, the cumulative rate of death due to solid tumors was significantly higher in patients with sMPMTs than those without sMPMTs (high tumor burden: 26.7% vs. 1.6%, P < 0.001; low tumor burden: 12.7% vs. 1.0%, P = 0.003). The presence of sMPMTs did not have a significant impact on outcomes in patients with diffuse large B-cell lymphoma (DLBCL) (5-year OS: 65.4% and 66.9%, respectively; P = 0.74; 5-year progression-free survival [PFS]: 65.5% and 59.9%, respectively; P = 0.65). However, the cumulative rate of death from solid tumor in patients with sMPMTs was significantly higher than in patients without sMPMTs (5-year cumulative rate: 7.4% and 2.1%, respectively; P = 0.004). The treatment sequence did not have a significant effect on outcomes or the relative dose intensity of chemotherapy. Conclusions In patients with indolent lymphoma, those with sMPMTs had a significantly worse prognosis than those without sMPMTs, mainly because of high mortality due to solid tumors. The presence of sMPMTs was not a significant prognostic factor in patients with DLBCL. It is important to assess the status and need for early treatment of each type of malignancy in patients with sMPMTs.

ObjectiveThe prognosis of patients with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL) is poor. Although patients who fail first-line salvage chemotherapy are candidates for second-line salvage chemotherapy, the optimal treatment strategy for these patients has not yet been established.MethodsThe present, single-center, retrospective study included transplant-eligible patients with R/R DLBCL who received second-line salvage chemotherapy with curative intent.ResultsSeventy-six patients with R/R DLBCL received second-line salvage chemotherapy. Eighteen (23.7%) patients were responders to the first-line salvage chemotherapy. The overall response rate was 39.5%, and overall survival (OS) was significantly longer in patients who responded to second-line salvage chemotherapy than those who did not. Forty-one patients who proceeded to potentially curative treatment (autologous hematopoietic stem cell transplantation [ASCT], chimeric antigen receptor [CAR] T-cell therapy, or allogeneic hematopoietic stem cell transplantation) had a better prognosis than those who did not. Among the 46 patients who failed to respond to the second-line salvage regimen, only 18 (39.1%) could proceed to the curative treatments. However, among the 30 patients who responded to the second-line salvage regimen, 23 (76.7%) received one of the potentially curative treatments. Among 34 patients who received CAR T-cell therapy, OS was significantly longer in those who responded to salvage chemotherapy immediately prior to CAR T-cell therapy than in those who did not respond. In contrast, the number of prior lines of chemotherapy was not identified as a statistically significant prognostic factor of survival. No significant difference was detected in OS between patients receiving ASCT and those receiving CAR T-cell therapy after the response to second-line salvage chemotherapy.DiscussionIn this study, we demonstrated that chemosensitivity remained a crucial factor in predicting survival outcomes following CAR T-cell therapy irrespective of the administration timing, and that both ASCT and CAR T-cell therapy were acceptable after the response to second-line salvage chemotherapy.

Peripheral T‐cell lymphoma (PTCL) is a heterogeneous group of aggressive lymphomas with a poor prognosis. The International Prognostic Index (IPI) and the Prognostic Index for PTCL‐unspecified (PIT) is used to predict the prognosis of PTCL. The hemoglobin‐platelet index (HPI), based on anemia and thrombocytopenia status, is associated with the prognosis of diffuse large B‐cell lymphoma. However, its significance in terms of predicting the prognosis of PTCL has not been fully investigated. We herein retrospectively analyzed 100 patients with newly diagnosed PTCL in our department. At a median follow‐up of 3.2 years, the median progression‐free survival (PFS) and overall survival (OS) was 0.72 (95% confidence interval [CI]: 0.56–1.2) years and 2.0 (95% CI: 1.5–4.7) years, respectively. Multivariate analysis revealed that elevated lactic dehydrogenase (LDH) and hypoalbuminemia were independent adverse variables for PFS. The HPI showed significant predictive value for both PFS and OS. As a new prognostic model comprising the HPI, LDH, and albumin, the LA‐HPI allowed the stratification of patients into four distinct risk subgroups: low risk (zero risk factors), low‐intermediate risk (one risk factors), high‐intermediate risk (two or three risk factors), or high risk (four risk factors). The PFS and OS differed significantly among the patients by the LA‐HPI score. The LA‐HPI demonstrated better predictive performance compared to the IPI, PIT, and HPI. Our data demonstrated the prognostic utility of the HPI in patients with PTCL. The LA‐HPI, incorporating four readily obtainable parameters, exhibited superior performance compared to traditional indices.

INTRODUCTION: Japan is a developed country with high use of Internet and online platforms for health information. ‘Yahoo! Answer Japan’ is the most commonly used question-and-answer service in Japan.AIM: To explore the information users seek regarding breast cancer from the ‘Yahoo! Answer Japan’ web portal.METHODS: The ‘Yahoo! Answer Japan’ portal was searched for the key word ‘breast cancer’ and all questions searched for the period of 1 January to 31 December 2014 were obtained. The selected questions related to human breast cancer and were not advertisements or promotional material. The questions were categorized using a coding schema. High and low access of the questions were defined by the number of view-counts.RESULTS: Among the 2392 selected questions, six major categories were identified; (1) suspected breast cancer, (2) breast cancer screening, (3) treatment of breast cancer, (4) life with breast cancer, (5) prevention of breast cancer and (6) others. The highest number of questions were treatment related (28.8%) followed by suspected breast cancer-related questions (23.4%) and screening-related questions (20%). Statistical analysis revealed that the treatment-related questions were more likely to be highly accessed.CONCLUSION: Content analysis of Internet question–answer communities is important, as questions posted on these sites would serve as a rich source of direct reflection regarding the health-related information needs of the general population.

The optimal dose intensity of chemotherapy for elderly patients with diffuse large B cell lymphoma (DLBCL) remains controversial because of concerns about adverse events and comorbidities related to the patients’ frailty. This single-center study retrospectively analyzed patients aged ≥ 70 years who were newly diagnosed with DLBCL and received chemotherapy between 2004 and 2022. Survival outcomes and treatment-related mortality (TRM) were stratified according to geriatric assessment variables, and the influence of chemotherapy dose intensity on outcomes was assessed using the frailty score with a Cox hazards model with restricted cubic spline (RCS) in patients aged 70–79 years. In total, 337 patients were included. The frailty score accurately predicted prognosis (5-year overall survival [OS]: 73.1%, 60.2%, and 29.7% in fit, unfit, and frail patients, respectively; P < 0.001) and TRM (5-year TRM: 0%, 5.4%, and 16.8 in fit, unfit, and frail patients, respectively; P < 0.001). Cox regression with RCS demonstrated a linear association between dose intensity and survival outcomes. Initial dose intensity (IDI) and relative dose intensity (RDI) had a significant impact on OS in fit patients. However, IDI and RDI had no significant effect on survival in non-fit (unfit and frail) patients. The frailty score identified non-fit patients with poorer survival and a higher risk of TRM. While fit patients were likely to benefit from full-dose R-CHOP, unfit and frail patients would likely benefit more from attenuated R-CHOP. This study suggested a potential role for the frailty score in individualizing treatment intensity in elderly patients with DLBCL.

Key Points Cortical thymic epithelial cells (cTECs) are functionally heterogeneous, although T cell-lineage-specifying and positive-selection-inducing functions seem to overlap between individual cTECs. Thymic nurse cells are a subpopulation of cTECs that are morphologically and functionally specialized for optimizing the positive selection of thymocytes. Promiscuous gene expression in individual medullary TECs (mTECs) is heterogeneous, and mosaic expression across all mTECs constitutes a pool of the promiscuously expressed genes. CC-chemokine ligand 21 (CCL21)-expressing mTECs represent a functionally mature mTEC low subpopulation and resemble post-autoimmune regulator (AIRE) mTECs. Embryonic TEC progenitors acquire hallmarks of the cTEC lineage and then the mTEC lineage in a stepwise manner during initial thymus cortex and medulla formation. A self-renewing subset of embryonic TECs, referred to as mTEC stem cells, has been identified that are capable of long-term and specific generation of mTECs. The generation of a diverse T cell repertoire depends on heterogeneous populations of thymic epithelial cells (TECs). Here, the authors explain how different subsets of TECs support and coordinate different stages of T cell development to ensure the selection of a functional and self-tolerant T cell repertoire. In the thymus, diverse populations of thymic epithelial cells (TECs), including cortical and medullary TECs and their subpopulations, have distinct roles in coordinating the development and repertoire selection of functionally competent and self-tolerant T cells. Here, we review the expanding diversity in TEC subpopulations in relation to their functions in T cell development and selection as well as their origins and development.

Background: Logistic regression models are widely used to evaluate the association between a binary outcome and a set of covariates. However, when there are few study participants at the outcome and covariate levels, the models lead to bias of the odds ratio (OR) estimated using the maximum likelihood (ML) method. This bias is known as sparse data bias, and the estimated OR can yield impossibly large values because of data sparsity. However, this bias has been ignored in most epidemiological studies.Methods: We review several methods for reducing sparse data bias in logistic regression. The primary aim is to evaluate the Bayesian methods in comparison with the classical methods, such as the ML, Firth’s, and exact methods using a simulation study. We also apply these methods to a real data set.Results: Our simulation results indicate that the bias of the OR from the ML, Firth’s, and exact methods is considerable. Furthermore, the Bayesian methods with hyper-ɡ prior modeling of the prior covariance matrix for regression coefficients reduced the bias under the null hypothesis, whereas the Bayesian methods with log F-type priors reduced the bias under the alternative hypothesis.Conclusion: The Bayesian methods using log F-type priors and hyper-ɡ prior are superior to the ML, Firth’s, and exact methods when fitting logistic models to sparse data sets. The choice of a preferable method depends on the null and alternative hypothesis. Sensitivity analysis is important to understand the robustness of the results in sparse data analysis.

The thymus supports multiple αβ T cell lineages that are functionally distinct, but mechanisms that control this multifaceted development are poorly understood. Here we examine medullary thymic epithelial cell (mTEC) heterogeneity and its influence on CD1d-restricted iNKT cells. We find three distinct mTEC low subsets distinguished by surface, intracellular and secreted molecules, and identify LTβR as a cell-autonomous controller of their development. Importantly, this mTEC heterogeneity enables the thymus to differentially control iNKT sublineages possessing distinct effector properties. mTEC expression of LTβR is essential for the development thymic tuft cells which regulate NKT2 via IL-25, while LTβR controls CD104 + CCL21 + mTEC low that are capable of IL-15-transpresentation for regulating NKT1 and NKT17. Finally, mTECs regulate both iNKT-mediated activation of thymic dendritic cells, and iNKT availability in extrathymic sites. In conclusion, mTEC specialization controls intrathymic iNKT cell development and function, and determines iNKT pool size in peripheral tissues. Thymus is a unique environment hosting the development of many T cell subsets with distinct functions. Here the authors show that medullary thymic epithelial cells (mTEC) are functionally diverse, with LTβR signaling serving differential regulation of mTEC for specific control of multiple lineages of invariant natural killer T cells.