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Studies in different animal model systems have revealed the impact of odors on immune cells; however, any understanding on why and how odors control cellular immunity remained unclear. We find that Drosophila employ an olfactory-immune cross-talk to tune a specific cell type, the lamellocytes, from hematopoietic-progenitor cells. We show that neuronally released GABA derived upon olfactory stimulation is utilized by blood-progenitor cells as a metabolite and through its catabolism, these cells stabilize Sima/HIFα protein. Sima capacitates blood-progenitor cells with the ability to initiate lamellocyte differentiation. This systemic axis becomes relevant for larvae dwelling in wasp-infested environments where chances of infection are high. By co-opting the olfactory route, the preconditioned animals elevate their systemic GABA levels leading to the upregulation of blood-progenitor cell Sima expression. This elevates their immune-potential and primes them to respond rapidly when infected with parasitic wasps. The present work highlights the importance of the olfaction in immunity and shows how odor detection during animal development is utilized to establish a long-range axis in the control of blood-progenitor competency and immune-priming.

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Background: Improved cancer survival in patients treated with thoracic ionizing radiation (XRT) has resulted in unanticipated surge of aortic stenosis. Transcatheter aortic valve replacement (TAVR) has revolutionized the management of severe aortic stenosis. However, long-term clinical outcomes in radiation-exposed cohorts undergoing TAVR are unknown. We compared the all-cause mortality and major adverse cardiac events (MACE) in patients with prior chest XRT (C-XRT) undergoing TAVR. Methods: This is an observational cohort study in subjects who underwent TAVR for symptomatic severe aortic stenosis from 2012 to 2017 in a tertiary care referral center. We examined the all-cause mortality and MACE using cox proportional hazard analysis to identify the clinical predictors of survival in the cohort of patients who had a history of prior C-XRT for malignancy.Results: Of the 610 patients who underwent TAVR for symptomatic severe aortic stenosis, 75 had prior C-XRT. The majority of C-XRT patients had prior breast cancer (44%) followed by Hodgkin's lymphoma (31%), with the median time from XRT to TAVR of 19.0 years. During a mean follow up of 17.1 months after TAVR, all-cause mortality was 17%. Those with prior C-XRT had higher all-cause mortality (XRT: 29%; non-XRT:15%, p < 0.01) and MACE (XRT: 57%; non-XRT: 27%, p < 0.001) after TAVR. Patients with prior XRT had a higher incidence of atrial fibrillation (XRT: 48%; non-XRT: 2.4%, p < 0.01) and high-grade heart block (XRT: 20%; non-XRT: 9.1%, p = 0.007) requiring pacemaker implant after TAVR. On multivariate cox proportional hazard analysis, prior XRT (HR: 2.07, p = 0.003), poor renal function (HR: 1.29, p < 0.001) and post-operative anemia requiring transfusion (HR: 1.16, p:0.001) were the strongest predictors of reduced survival. Conclusions: Cancer survivors with prior C-XRT have higher incidence of all-cause mortality and MACE after TAVR. Careful patient selection and follow-up strategies are needed to improve outcomes.

BackgroundImmune checkpoint inhibitors (ICI) have emerged as a front-line therapy for a variety of solid tumors. With the widespread use of these agents, immune-associated toxicities are increasingly being recognized, including fatal myocarditis. There are limited data on the outcomes and prognostic utility of biomarkers associated with ICI-associated myocarditis. Our objective was to examine the associations between clinical biomarkers of cardiomyocyte damage and mortality in patients with cancer treated with ICIs.MethodsWe retrospectively studied 23 patients who developed symptomatic and asymptomatic troponin elevations while receiving ICI therapy at a National Cancer Institute-designated comprehensive cancer center. We obtained serial ECGs, troponin I, and creatine kinase-MD (CK-MB), in addition to other conventional clinical biomarkers, and compared covariates between survivors and non-survivors.ResultsAmong patients with myocarditis, higher troponin I (p=0.037) and CK-MB (p=0.034) levels on presentation correlated with progression to severe myocarditis. Higher troponin I (p=0.016), CK (p=0.013), and CK-MB (p=0.034) levels were associated with increased mortality, while the presence of advanced atrioventricular block on presentation (p=0.088) trended toward increased mortality. Weekly troponin monitoring lead to earlier hospitalization for potential myocarditis (p=0.022) and was associated with decreased time to steroid initiation (p=0.053) and improved outcomes.ConclusionsRoutine troponin surveillance may be helpful in predicting mortality in ICI-treated patients with cancer in the early phase of ICI therapy initiation. Early detection of troponin elevation is associated with earlier intervention and improved outcomes in ICI-associated myocarditis. The recommended assessment and diagnostic studies guiding treatment decisions are presented.

Background Women continue to be underrepresented in cardiology and even more so in leadership positions. We evaluated the trends and gender differences in the guideline writing groups of the American College of Cardiology/American Heart Association (ACC/AHA), Canadian Cardiovascular Society (CCS), and European Society of Cardiology (ESC) guidelines from 2006 to 2020. Methods and Results We extracted all guidelines authors from 2006 to 2020, assessed their gender from publicly available profiles, and compared differences based on subspecialties and specific societies. Stratified and trend analyses were performed using χ 2 and average annual percentage change/average 5 year percentage change. A total of 80 ACC/AHA (1288 authors [28% women]), 64 CCS (988 authors [26% women]), and 59 ESC (1157 authors [16% women]) guidelines were analyzed. A significant increase in inclusion of women was seen in ACC/AHA (12.6% [2006] to 42.6% [2020]; average annual percentage change, 6.6% [2.3% to 11.1%]; P =0.005) and ESC (7.1% [2006] to 25.8% [2020]; average annual percentage change, 6.6% [0.2% to 13.5%]; P =0.04), but the trend remained similar in CCS (20.6% [2006] to 36.3% [2020]; average annual percentage change, −0.1% (−3.7% to 3.5%); P =0.94), guideline authors. More women were coauthors in the ACC/AHA and ESC guidelines when women were chairs of guidelines. There was a persistent disparity of women among guideline authors for general cardiology and all subspecialties, except for pediatric cardiology and heart failure guidelines. The appointment of women authors as a chair was significantly low in all societies (22.4% [ACC/AHA], 16.9% [CCS], and 7.2% [ESC]; P =0.008). Conclusions There is a significant disparity in the inclusion of women on all national guideline committees, in addition to serving as a chair of cardiology guidelines. Further advocacy is required to promote equity, diversity, and inclusion in our cardiology guidelines globally.

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Newly diagnosed adult patients with Philadelphia chromosome positive chronic myeloid leukemia in chronic phase. Follow-up is limited to 5 years. 1.2 Ph+ CML in Blast Crisis (BC), Accelerated Phase (AP) or Chronic Phase (CP) After Interferon-alpha (IFN) Therapy Patients with Philadelphia chromosome positive chronic myeloid leukemia in blast crisis, accelerated phase, or in chronic phase after failure of interferon-alpha therapy. 1.3 Pediatric Patients with Ph+ CML in Chronic Phase Pediatric patients with Ph+ CML in chronic phase who are newly diagnosed or whose disease has recurred after stem cell transplant or who are resistant to interferon-alpha therapy. There are no controlled trials in pediatric patients demonstrating a clinical benefit, such as improvement in disease-related symptoms or increased survival. 1.4 Ph+ Acute Lymphoblastic Leukemia (ALL) Adult patients with relapsed or refractory Philadelphia chromosome positive acute lymphoblastic leukemia 1.5 Myelodysplastic/Myeloproliferative Diseases (MDS/MPD) Adult patients with myelodysplastic/ myeloproliferative diseases associated with PDGFR (platelet-derived growth factor receptor) gene rearrangements 1.6 Aggressive Systemic Mastocytosis (ASM) Adult patients with aggressive systemic mastocytosis without the D816V c-Kit mutation or with c-Kit mutational status unknown 1.7 Hypereosinophilic Syndrome (HES) and/or Chronic Eosinophilic Leukemia (CEL) Adult patients with hypereosinophilic syndrome and/or chronic eosinophilic leukemia who have the FIP1L1-PDGFRα fusion kinase (mutational analysis or FISH demonstration of CHIC2 allele deletion) and for patients with HES and/or CEL who are FIP1L1-PDGFRα fusion kinase negative or unknown 1.8 Dermatofibrosarcoma Protuberans (DFSP) Adult patients with unresectable, recurrent and/or metastatic dermatofibrosarcoma protuberans