Heterozygosity for Roquinsan leads to angioimmunoblastic T-cell lymphoma-like tumors in mice

Angioimmunoblastic T-cell lymphoma (AITL) is the second most common peripheral T-cell lymphoma with unusual clinical and pathologic features and a poor prognosis despite intensive chemotherapy. Recent studies have suggested AITL derives from follicular helper T (T(FH)) cells, but the causative molecular pathways remain largely unknown. Here we show that approximately 50% of mice heterozygous for the "san" allele of Roquin develop tumors accompanied by hypergammaglobulinemia by 6 months of age. Affected lymph nodes displayed the histologic features diagnostic of AITL, except for the presence of expanded FDC networks. Accumulation of T(FH) cells preceded tumor development, and clonal rearrangements in the TCR-β genes were present in most tumors. Furthermore, T(FH) cells exhibited increased clonality compared with non-T(FH) cells from the same lymph nodes, even in the absence of tumors. Genetic manipulations that prevent T(FH) development, such as deletion of ICOS, CD28, and SAP, partially or completely abrogated tumor development, confirming a T(FH)-derived origin. Roquin(san/+) mice emerge as a useful model to investigate the molecular pathogenesis of AITL and for preclinical testing of therapies aimed at targeting dysregulated T(FH) cells or their consequences.     

Use of pegfilgrastim primary prophylaxis and risk of infection,by chemotherapy cycle and regimen,among patients with breast cancer or non-Hodgkin’s lymphoma

Purpose

This study aims to examine granulocyte colony-stimulating factor (G-CSF) prophylaxis by cancer type, chemotherapy regimen, and cycle in a real-world setting to assess if practice conforms to clinical guidelines, which recommend G-CSF prophylaxis every cycle when a patient’s risk of febrile neutropenia (FN) is 20 % or greater, and to describe the incidence of FN among patients who discontinue pegfilgrastim (peg) prophylaxis.

Methods

The cohort was selected from administrative claims data and includes adults diagnosed with non-Hodgkin’s lymphoma (NHL) or breast cancer (BC) who began chemotherapy 2005–2010.

Results

About 83.2 % of the 4,470 patients with BC treated with dose-dense doxorubicin, cyclophosphamide (ddAC), 83.6 % of 2,197 patients with BC treated with docetaxel, doxorubicin, cyclophosphamide (TAC), and about 55.6 % of the 2,722 patients with NHL treated with cyclophosphamide, doxorubicin, vincristine, with or without prednisone for 3-week cycles (CHOP-R Q3W) received peg prophylaxis in cycle 1. Among patients on these regimens who received peg prophylaxis in cycle 1 and were still on the regimen in cycle 4, about 90 % received peg prophylaxis in that cycle. Among patients with BC or NHL who discontinued G-CSF, the incidence proportion of infection or FN varied by regimen and cycle, with a range from 0 to 14 %.

Conclusions

Despite clinical guidelines recommending G-CSF prophylaxis with chemotherapy regimens with a high risk of FN, many NHL and BC patients do not receive FN prophylaxis in cycle 1. However, among patients who receive G-CSF in cycle 1 and remain on the regimen, the majority appear to continue prophylaxis as indicated.     

The influence of the ambient temperature on blood pressure and how it will affect the epidemiology of hypertension in Asia

Epidemiologic studies have consistently demonstrated an increased risk of cardiovascular disease during colder temperatures. Hemodynamic changes associated with cold temperature and an increase in thrombogenicity may both account for the increase in cardiovascular risk and mortality. Studies using both in‐office and out‐of‐office BP measurements have consistently shown an elevation in BP during the colder seasons. The large difference in BP between cold and warm months may increase the incidence of hypertension and reduce the hypertension control rate, potentially resulting in increased cardiovascular risk, especially among those at risk of cardiovascular disease. The current trends in global warming and climate change may have a profound impact on the epidemiology of hypertension and cardiovascular disease, as changes in the climate may significantly affect both BP variability and cardiovascular disease, especially in those with high cardiovascular risk and the elderly. Furthermore, climate change could have a significant influence on hypertension in Asia, considering the unique characteristics of hypertensive patients in Asia. As an increase in ambient temperature decreases the mean daytime average and morning surge in BP, but increases the nocturnal BP, it is difficult to predict how environmental changes will affect the epidemiology and prognosis of hypertension in the Asian‐Pacific region. However, these seasonal variations in BP could be minimized by adjusting the housing conditions and using anticipation medicine. In this review, we discuss the impact of seasonal variation in the ambient temperature on hypertension and cardiovascular disease and discuss how this may impact the epidemiology of hypertension and cardiovascular disease.     

COVID‐19 and older people in Asia: Asian Working Group for Sarcopenia calls to action

The coronavirus disease 2019 (COVID‐19) pandemic has casted a huge impact on global public health and the economy. In this challenging situation, older people are vulnerable to the infection and the secondary effects of the pandemic and need special attention. To evaluate the impacts of COVID‐19 on older people, it is important to balance the successful pandemic control and active management of secondary consequences. These considerations are particularly salient in the Asian context, with its diversity among countries in terms of sociocultural heritage, healthcare setup and availability of resources. Thus, the Asian Working Group for Sarcopenia summarized the considerations of Asian countries focusing on responses and difficulties in each country, impacts of health inequity related to the COVID‐19 pandemic and proposed recommendations for older people, which are germane to the Asian context. More innovative services should be developed to address the increasing demands for new approaches to deliver healthcare in these difficult times and to establish resilient healthcare systems for older people. Geriatr Gerontol Int 2020; 20: 547–558 .