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BACKGROUND Idiopathic multicentric Castleman disease (iMCD) is a hematologic illness involving cytokine-induced lymphoproliferation, systemic inflammation, cytopenias, and life-threatening multi-organ dysfunction. The molecular underpinnings of interleukin-6 (IL-6) blockade–refractory patients remain unknown; no targeted therapies exist. In this study, we searched for therapeutic targets in IL-6 blockade–refractory iMCD patients with the thrombocytopenia, anasarca, fever/elevated C-reactive protein, reticulin myelofibrosis, renal dysfunction, organomegaly (TAFRO) clinical subtype.

Background Parkinsonian signs are common, non-specific findings in older adults and associated with increased rates of dementia and mortality. It is important to understand which motor outcomes are associated with parkinsonian signs. Objectives To determine the role of parkinsonian signs on fall rates among older adults. Methods We conducted a longitudinal study of primary care patients from the University of Pennsylvania Health System. Adults over 55 years were assessed at baseline through surveys and a neurological examination. We recorded falls over the following 2 years. Parkinsonian signs were defined as the presence of 2 of 4 cardinal signs. Incident falls were compared between subjects with and without parkinsonian signs, and modified Poisson regression used to adjust for potential confounders in the relationship between parkinsonian signs and falls. Results 982 subjects with a mean age of 68 (s.d. 8.8) years participated. 29% of participants fell and 12% exhibited parkinsonian signs at baseline. The unadjusted RR for falls among individuals with parkinsonian signs was 1.36 (95% CI 1.05–1.76, p = 0.02). After adjusting for age, cognitive function, urinary incontinence, depression, diabetes, stroke and arthritis, individuals with parkinsonian signs were still 38% more likely to fall than those without parkinsonian signs (RR 1.38, 95% CI 1.04–1.82; p = 0.03). Falls among those with parkinsonian signs were more likely to lead to injury (53% vs 37%; p = 0.04). Conclusions Parkinsonian signs are a significant, independent risk factor for falls. Early detection of this clinical state is important in order to implement fall prevention programs among primary care patients.

Castleman disease (CD) describes a group of heterogeneous hematologic disorders with characteristic histopathological features. CD can present with unicentric or multicentric (MCD) regions of lymph node enlargement. Some cases of MCD are caused by human herpesvirus-8 (HHV-8), whereas others are HHV-8–negative/idiopathic (iMCD). Treatment of iMCD is challenging, and outcomes can be poor because no uniform treatment guidelines exist, few systematic studies have been conducted, and no agreed upon response criteria have been described. The purpose of this paper is to establish consensus, evidence-based treatment guidelines based on the severity of iMCD to improve outcomes. An international Working Group of 42 experts from 10 countries was convened by the Castleman Disease Collaborative Network to establish consensus guidelines for the management of iMCD based on published literature, review of treatment effectiveness for 344 cases, and expert opinion. The anti–interleukin-6 monoclonal antibody siltuximab (or tocilizumab, if siltuximab is not available) with or without corticosteroids is the preferred first-line therapy for iMCD. In the most severe cases, adjuvant combination chemotherapy is recommended. Additional agents are recommended, tailored by disease severity, as second- and third-line therapies for treatment failures. Response criteria were formulated to facilitate the evaluation of treatment failure or success. These guidelines should help treating physicians to stratify patients based on disease severity in order to select the best available therapeutic option. An international registry for patients with CD (ACCELERATE, #NCT02817997) was established in October 2016 to collect patient outcomes to increase the evidence base for selection of therapies in the future.