The association between kidney function and cancer incidence is inconsistent among previous reports, and data on the Japanese population are lacking. It is unknown whether kidney function modifies the cancer risk of other factors. We aimed to evaluate the association of estimated glomerular filtration rate (eGFR) with cancer incidence and mortality in 55 242 participants (median age, 57 years; 55% women) from the Japan Multi-Institutional Collaborative Cohort Study. We also investigated differences in cancer risk factors between individuals with and without kidney dysfunction. During a median 9.3-year follow-up period, 4278 (7.7%) subjects developed cancer. Moderately low and high eGFRs were associated with higher cancer incidence; compared with eGFR of 60-74 ml/min/1.73 m2, the adjusted hazard ratios (HRs) (95% confidence intervals [CIs]) for eGFRs of ≥90, 75-89, 45-59, 30-44 and 10-29 ml/min/1.73 m2 were 1.18 (1.07-1.29), 1.09 (1.01-1.17), 0.93 (0.83-1.04), 1.36 (1.00-1.84) and 1.12 (0.55-2.26), respectively. High eGFR was associated with higher cancer mortality, while low eGFR was not; the adjusted subdistribution HRs (95% CIs) for eGFRs of ≥90 and 75-89 ml/min/1.73 m2 were 1.58 (1.29-1.94) and 1.27 (1.08-1.50), respectively. Subgroup analyses of participants with eGFRs ≥60 and <60 ml/min/1.73 m2 revealed elevated cancer risks of smoking and family history of cancer in those with eGFR <60 ml/min/1.73 m2, with significant interactions. Our findings suggest that the relationship between eGFR and cancer incidence was U-shaped. Only high eGFR was associated with cancer mortality. Kidney dysfunction enhanced cancer risk from smoking. 相似文献
An aging population has prompted us to evaluate the indications of liver transplantation (LT) in elderly patients more frequently. In this review, we summarize the short- and long-term results after LT in elderly patients and also discuss the criteria used to select patients and how recipient age can challenge current allocation systems. Briefly, the feasibility and early outcomes of LT in elderly patients compare favorably with those of younger patients. Although long-term survival is less than satisfactory, large-scale studies show that the transplant survival benefit is similar for elderly and younger patients. Therefore, age alone does not contraindicate LT; however, screening for cardiopulmonary comorbidities, and asymptomatic malignancies, evaluating nutritional status, and frailty, is crucial to ensure optimal results and avoid futile transplantation. 相似文献
Foxp3‐expressing regulatory T (Treg) cells, which are indispensable for preventing autoimmunity, also suppress effective tumor immunity. Treg cells abundantly infiltrate into tumor tissues, which is often associated with poor prognosis in cancer patients. Removal of Treg cells enhances anti‐tumor immune responses but may also elicit autoimmunity. A key issue in devising Treg‐targeting cancer immunotherapy is, therefore, how to specifically deplete Treg cells infiltrating into tumor tissues without affecting tumor‐reactive effector T cells, while suppressing autoimmunity. This can be achieved by differentially controlling Treg and effector T cells by various ways. In this review, we discuss how tumor‐infiltrating Foxp3+ Treg cells hamper effective anti‐tumor immune responses especially in tumor tissues and how they can be specifically targeted for augmenting tumor immunity but not autoimmunity. 相似文献
To effectively engage patients in clinical decisions regarding the management of teeth with apical periodontitis (AP), there is a need to explore patients' perspectives on the decision-making process. This study surveyed patients for their preferred level of participation in making treatment decisions for a tooth with AP.
Methods
Data were collected through a mail-out survey of 800 University of Toronto Faculty of Dentistry patients, complemented by a convenience sample of 200 patients from 10 community practices. The Control Preferences Scale was used to evaluate the patients' preferences for active, collaborative, or passive participation in treatment decisions for a tooth with AP. Using bivariate and logistic regression analyses, the Gelberg-Andersen Behavioral Model for Vulnerable Populations was applied to the Control Preferences Scale questions to understand the influential factors (P ≤ .05).
Results
Among 434 of 1,000 respondents, 44%, 40%, and 16% preferred an active, collaborative, and passive participation, respectively. Logistic regression showed a significant association (P ≤ .025) between participants' higher education and preference for active participation compared with a collaborative role. Also, immigrant status was significantly associated with preference for passive participation (P = .025).
Conclusions
The majority of patients valued an active or collaborative participation in deciding treatment for a tooth with AP. This pattern implied a preference for a patient-centered practice mode that emphasizes patient autonomy in decision making. 相似文献
Brain metastases are common complication in cancer patients. Immune checkpoint inhibitors show therapeutic benefits also in patients with central nervous system (CNS) metastases. However, their antitumor effects on metastatic tumors and their underlying mechanisms are still poorly understood. In this study we investigated the antitumor effect of anti-programmed death-ligand 1 (PD-L1) antibody on metastatic brain tumors and evaluated immune responses during treatment. We employed a hematogenous brain metastasis xenograft model using immunodeficient mice with murine lymphocyte infusions. A human non-small-cell lung cancer (NSCLC) cell line stably expressing NanoLuc® reporter (Nluc-H1915) was inoculated from the internal carotid artery of SCID mice. After metastases were established (24 days after inoculation), splenocytes prepared from H1915-immunized BALB/c mice were injected intravenously and mouse IgG or anti-PD-L1 antibody treatment was started (day 1). Evaluated by Nluc activity, tumor volume in the brain on day 14 was significantly lower in anti-PD-L1-treated mice than in mouse IgG-treated mice. Furthermore CD8+ cells were primarily infiltrated intratumorally and peritumorally and anti-PD-L1 treatment induced a significantly higher proportion of Granzyme B (GzmB)+ cells among CD8+ T cells. The antitumor effect of anti-PD-L1 antibody on brain metastasis is thought to be achieved by the enhanced activation of infiltrated CD8+ T cells into metastatic brain tumor. These results suggest that anti-PD-L1 antibody-containing regimens may be promising treatment options for cancer patients with brain metastases.
Allogeneic bone marrow or blood stem cell transplantation (BMT) represents an important therapeutic tool for treatment of otherwise incurable malignant and non-malignant diseases. Until recently, autologous and allogeneic bone marrow or mobilized blood stem cells transplantation were used primarily to replace malignant, genetically abnormal or deficient immunohematopoietic compartment and therefore, highly toxic myeloablative regimen were considered mandatory for more effective eradication of all undesirable host-derived hematopoietic elements. Our preclinical and ongoing clinical studies indicated that much more effective eradication of host immunohematopoietic system cells could be achieved by adoptive allogeneic cell therapy with donor lymphocyte infusion following BMT. Thus, eradication of blood cancer cells, especially in patients with CML and less frequently in patients with other hematologic malignancies, could be frequently accomplished despite complete resistance of such tumor cells to maximally tolerated doses of chemoradiotherapy. Our cumulative experience suggested that graft versus leukemia (GVL) effects might be a useful tool for eradication of otherwise resistant tumor cells of host origin. Based on the cumulative clinical experience and experimental data in animal models of human diseases it appears that induction of host versus graft tolerance as step one, may allow durable engraftment of donor immunocompetent lymphocytes, which may be used for induction of effective biologic warfare against host-type immunohematopoietic cells that need to be replaced, malignant, genetically abnormal or self-reactive alike. Based on the aforementioned rationale, we speculated that the therapeutic benefit of BMT may be improved by using a safer conditioning as part of the transplant procedure, with the goal in mind to induce host versus graft tolerance to enable subsequent induction of GVL, possibly graft versus tumor or even graft versus autoimmunity effects, rather than attempt to eliminate host cells with hazardous myeloablative chemoradiotherapy. The latter hypothesis suggested that effective BMT procedure may be accomplished without lethal conditioning of the host, using new well tolerated non-myeloablative regimen, thus possibly minimizing immediate and late side effects related to myeloablative procedures considered until recently mandatory for conditioning of BMT recipients. Recent clinical data that will be presented suggests that effective BMT procedures may be accomplished with well-tolerated non-myeloablative stem cell transplantation (NST) regimen, with no major toxicity. Thus, new NST approaches may offer the feasibility of safer BMT procedure for a large spectrum of clinical indications in children and elderly individuals without lower or upper age limit, while minimizing procedure-related toxicity and mortality. Taken together, our cumulative data suggest that high dose chemotherapy and radiation therapy may be successively replaced by a more effective biologic tool, alloreactive donor lymphocytes, thus setting the stage for innovative therapeutic procedures for safer and more effective treatment of patients in need of BMT. 相似文献