IL-33 signaling contributes to the pathogenesis of myeloproliferative neoplasms

Myeloproliferative neoplasms (MPNs) are characterized by the clonal expansion of one or more myeloid cell lineage. In most cases, proliferation of the malignant clone is ascribed to defined genetic alterations. MPNs are also associated with aberrant expression and activity of multiple cytokines; however, the mechanisms by which these cytokines contribute to disease pathogenesis are poorly understood. Here, we reveal a non-redundant role for steady-state IL-33 in supporting dysregulated myelopoiesis in a murine model of MPN. Genetic ablation of the IL-33 signaling pathway was sufficient and necessary to restore normal hematopoiesis and abrogate MPN-like disease in animals lacking the inositol phosphatase SHIP. Stromal cell–derived IL-33 stimulated the secretion of cytokines and growth factors by myeloid and non-hematopoietic cells of the BM, resulting in myeloproliferation in SHIP-deficient animals. Additionally, in the transgenic JAK2^V617F model, the onset of MPN was delayed in animals lacking IL-33 in radio-resistant cells. In human BM, we detected increased numbers of IL-33–expressing cells, specifically in biopsies from MPN patients. Exogenous IL-33 promoted cytokine production and colony formation by primary CD34⁺ MPN stem/progenitor cells from patients. Moreover, IL-33 improved the survival of JAK2^V617F-positive cell lines. Together, these data indicate a central role for IL-33 signaling in the pathogenesis of MPNs.     

Speaking under pressure: Low linguistic complexity is linked to high physiological and emotional stress reactivity

What can a speech reveal about someone's state? We tested the idea that greater stress reactivity would relate to lower linguistic cognitive complexity while speaking. In Study 1, we tested whether heart rate and emotional stress reactivity to a stressful discussion would relate to lower linguistic complexity. In Studies 2 and 3, we tested whether a greater cortisol response to a standardized stressful task including a speech (Trier Social Stress Test) would be linked to speaking with less linguistic complexity during the task. We found evidence that measures of stress responsivity (emotional and physiological) and chronic stress are tied to variability in the cognitive complexity of speech. Taken together, these results provide evidence that our individual experiences of stress or “stress signatures”—how our body and mind react to stress both in the moment and over the longer term—are linked to how complex our speech under stress.     

Outcome and Prognostic Factors After Adrenalectomy for Patients with Distant Adrenal Metastasis

Background

The purpose of this study was to describe a single-institution experience with adrenal metastasectomy and to elucidate factors that may bear prognostic significance.

Methods

This is a single-center, retrospective review of patients with adrenal metastasis who underwent adrenalectomy performed with curative intent between 2000 and 2012. The Kaplan–Meier method was used to evaluate overall survival from time of adrenalectomy to death or last follow-up. Primary endpoint was death from any cause. Clinical variables were examined for association with survival.

Results

The study included 62 patients with mean age of 60 (±12) years; 55 % (34 of 62) were male, 85 % (53 of 62) presented with isolated adrenal metastasis, and 82 % (51 of 62) had metachronous disease with median disease-free interval (DFI) of 22 months (range, 6–217 months). Non-small cell lung cancer (NSCLC) was the most common primary comprising 50 % of cases. Median survival for the study population was 30 months (range, 1–145 months) and 5-year survival was 31 %. Patients with NSCLC had significantly shortened survival compared with non-NSCLC with median and 5-year survival of 17 versus 47 months and 27 % versus 38 %, respectively (p = .033). Synchronous metastasis (p = .028) and DFI < 12 months (p = .038) were also associated with worse survival outcome, though male gender (p = .69) and oligometastatic disease (p = .62) were not.

Conclusions

Adrenal metastasectomy resulted in median survival of 30 months and 5-year survival of 31 %. Shorter survival was associated with lung primary, short disease-free interval, and synchronous metastasis, but not with the presence of oligometastatic disease provided that the primary cancer and additional metastatic lesions were adequately controlled and amenable to resection.