Simultaneous ECG-gated PET imaging of multiple mice

IntroductionWe describe and illustrate a method for creating ECG-gated PET images of the heart for each of several mice imaged at the same time. The method is intended to increase “throughput” in PET research studies of cardiac dynamics or to obtain information derived from such studies, e.g. tracer concentration in end-diastolic left ventricular blood.MethodsAn imaging bed with provisions for warming, anesthetic delivery, etc., was fabricated by 3D printing to allow simultaneous PET imaging of two side-by-side mice. After electrode attachment, tracer injection and placement of the animals in the scanner field of view, ECG signals from each animal were continuously analyzed and independent trigger markers generated whenever an R-wave was detected in each signal. PET image data were acquired in “list” mode and these trigger markers were inserted into this list along with the image data. Since each mouse is in a different spatial location in the FOV, sorting of these data using trigger markers first from one animal and then the other yields two independent and correctly formed ECG-gated image sequences that reflect the dynamical properties of the heart during an “average” cardiac cycle.ResultsThe described method yields two independent ECG-gated image sequences that exhibit the expected properties in each animal, e.g. variation of the ventricular cavity volumes from maximum to minimum and back during the cardiac cycle in the processed animal with little or no variation in these volumes during the cardiac cycle in the unprocessed animal.ConclusionECG-gated image sequences for each of several animals can be created from a single list mode data collection using the described method. In principle, this method can be extended to more than two mice (or other animals) and to other forms of physiological gating, e.g. respiratory gating, when several subjects are imaged at the same time.     

Parents' drinking motives and problem drinking predict their children's drinking motives,alcohol use and substance misuse

The aim of the current study was to test the direct and indirect influence of parents' drinking motives and problem drinking on their children's drinking motives, alcohol use and substance misuse. Cross-sectional analysis of parent and child drinking patterns and motives, derived from the nationally representative Drinkaware Monitor panel survey. The sample comprised a total of 148 couples of parents and child. Path analysis revealed that children's alcohol use and substance misuse were influenced by their own drinking motives and parents' problem drinking. Parents' conformity motives were linked to their children's conformity motives. Finally, parental drinking problems mediated the effect of their coping motives on their childrens' alcohol use and substance misuse. In conclusion, parental drinking styles relate to their children's alcohol use and substance misuse through problem drinking and drinking motives.     

乳腺浸润性小叶癌的临床病理特征、诊疗现状及展望

乳腺癌是目前全球范围内发病率最高的恶性肿瘤，且组织学类型多样。乳腺浸润性小叶癌（ILC）是第二大常见浸润性乳腺癌组织学亚型（占5%~15%），近三十年来其发病率有所升高。E-钙黏蛋白表达缺失是乳腺ILC最主要的分子特征，可导致细胞间缺乏黏附性、肿瘤呈特殊弥漫性浸润生长，这给临床查体及影像学检查带来了一定挑战。尽管多数乳腺ILC患者激素受体呈阳性表达、对内分泌治疗反应良好，但也存在内分泌治疗耐药问题。此外，近年研究证实乳腺ILC患者预后并非如既往研究报道的那样良好，仅基于肿瘤分期及分子分型的治疗原则似乎并不完全适用于乳腺ILC，可能有必要将其作为独立的临床实体行进一步研究。本文主要综述了乳腺ILC的流行病学及临床特征、病理学及分子特征、诊断、治疗、预后、未来治疗方向等，以供临床医师更好地了解并优化乳腺ILC的临床诊断和个体化治疗参考。     

Impact of Socioeconomic Characteristics and Comorbidities on Therapy Initiation and Outcomes of Newly Diagnosed Multiple Myeloma: Real-World Data From a Resource-Constrained Setting

BackgroundOutcomes of newly diagnosed multiple myeloma (NDMM) in developing regions have not paralleled those in developed settings. Economic disadvantage, comorbidities, and aggressive disease behavior play competing roles on defining outcomes. Our aim was to analyze the impact of socioeconomic characteristics and comorbidities on therapy initiation, drug selection, and survival outcomes of NDMM in a resource-constrained setting.Patients and MethodsThis retrospective single-center cohort included ≥ 18-year-old NDMM patients from January 2006 to December 2018.ResultsA total of 245 patients were included with a median age of 62 years, Eastern Cooperative Oncology Group performance status ≤ 2 in 70.2%, International Staging System score ≥ 2 in 89.4%, and high-risk disease in 31.6%. Comorbidities were reported in 69.4%, and Charlson comorbidity index (CCI) was ≥ 2 in 64.1%. A total of 87.4% (n = 214) received thalidomide-, alkylating-, and bortezomib-based induction in 67.8%, 18.2%, and 13.1%. Patient-related factors including performance status, comorbidities, and CCI, but not myeloma-related factors, were associated with a decreased likelihood of initiating induction therapy. On multivariate analysis, CCI ≥ 2 remained statistically significant (odds ratio, 5.81; P = .005). Overall survival was 44 months. Although both patient- and myeloma-related factors were associated with a decreased overall survival, only International Staging System score > 2 (hazard ratio, 3.53; P = .004) and induction without bortezomib-based regimens (hazard ratio, 4.45; P < .001) were statistically significant on multivariate analysis.ConclusionMyeloma- and treatment-related factors are the main determinants of survival in NDMM induction-eligible patients. Patient-related factors play a pivotal role determining access to therapy and survival outcomes. Comorbidity index and performance status were determinant on defining therapy initiation in this real-world population, which emphasizes the need to improve health baseline conditions in resource-constrained settings.     

Maintenance Tyrosine Kinase Inhibitors Following Allogeneic Hematopoietic Stem Cell Transplantation for Chronic Myelogenous Leukemia: A Center for International Blood and Marrow Transplant Research Study

It remains unknown whether the administration of tyrosine kinase inhibitors (TKIs) targeting BCR-ABL1 after allogeneic hematopoietic cell transplantation (HCT) is associated with improved outcomes for patients with chronic myelogenous leukemia (CML). In this registry study, we analyzed clinical outcomes of 390 adult patients with CML who underwent transplantation between 2007 and 2014 and received maintenance TKI following HCT (n = 89) compared with no TKI maintenance (n = 301), as reported to the Center for International Blood and Marrow Transplant Research. All patients received TKI therapy before HCT. The majority of patients had a disease status of first chronic phase at HCT (n = 240; 62%). The study was conducted as a landmark analysis, excluding patients who died, relapsed, had chronic graft-versus-host disease, or were censored before day +100 following HCT. Of the 89 patients who received TKI maintenance, 77 (87%) received a single TKI and the other 12 (13%) received multiple sequential TKIs. The most common TKIs used for maintenance were dasatinib (n = 50), imatinib (n = 27), and nilotinib (n = 27). As measured from day +100, the adjusted estimates for 5-year relapse (maintenance, 35% versus no maintenance, 26%; P = .11), leukemia-free survival (maintenance, 42% versus no maintenance, 44%; P = .65), or overall survival (maintenance, 61% versus no maintenance, 57%; P = .61) did not differ significantly between patients receiving TKI maintenance or no maintenance. These results remained unchanged in multivariate analysis and were not modified by disease status before transplantation. In conclusion, our data from this day +100 landmark analysis do not demonstrate a significant impact of maintenance TKI therapy on clinical outcomes. The optimal approach to TKI administration in the post-transplantation setting in patients with CML remains undetermined.