Background Resection of diaphyseal bone tumors for local tumor control and stabilization often results in an intercalary skeletal defect and presents a reconstructive challenge for orthopaedic surgeons. Although many options for reconstruction have been described, relatively few studies report on the functional outcomes and complications of patients treated with modular intercalary endoprostheses. Questions/purposes The objectives of this study were to examine clinical outcomes after reconstruction with a modular intercalary endoprosthesis with a specific focus on (1) the rate of complication or failure; (2) differences in complication rates by anatomic site; (3) functional results as assessed by the Musculoskeletal Tumor Society System (MSTS); and (4) differences in complication rate between patients treated with cemented versus noncemented fixation. Methods We conducted a retrospective chart review of patients treated with a modular intercalary endoprosthesis from three musculoskeletal oncology centers from 2008 to 2013. The indication for use of this intercalary endoprosthesis was segmental bone loss from aggressive or malignant tumor with sparing of the joint above and below and deemed unsuitable for biologic reconstruction. No other implant was used for this indication during this period. During this period, 41 patients received a total of 44 intercalary implants, which included 18 (40%) humeri, 5 (11%) tibiae, and 21 (48%) femora. There were 27 (66%) men and 14 (34%) women with a mean age of 63 years (range, 18-91 years). Eight patients (20%) had primary bone tumors and 33 (80%) had metastatic lesions. Thirtyfive (85%) patients were being operated on as an initial treatment and six (15%) for revision of a previous reconstruction. Twenty-nine (66%) procedures had cemented stem fixation and 15 (34%) were treated with noncemented fixation. The overall mean followup was 14 months (range, 1-51 months). Patients with primary tumors had a mean followup of 19 months (range, 4-48 months) and patients One or more of the authors (JB) has received funding from the Musculoskeletal Transplant Foundation and has also received fees from Merete Inc (Berlin, Germany) and Implant Cast (Buxtehude, Germany) outside of the submitted work and holds several patents and licensing fees with CreOsso LLC (Montclair, NJ, USA with metastatic disease had a mean followup of 11 months (range, 1-51 months). Causes of implant failure were categorized according to Henderson et al. [19] into five types as follows: Type I (soft tissue failure), Type II (aseptic loosening), Type III (structural failure), Type IV (infection), and Type V (tumor progression). At 2 years of followup, 38 (93%) of these patients were accounted for with three (7%) lost to followup. MSTS functional assessment was available for 39 of 41 patients (95%). Results At latest followup of these 41 patients, 14 (34%) patients were dead of disease, two patients (5%) dead of other causes, seven (17%) are continuously disease-free, one (2%) shows no evidence of disease, a...

In this review, we examine the evidence that intestinal helminths can control harmful inflammatory responses and promote homeostasis by triggering systemic immune responses. Induction of separable components of immunity by helminths, which includes type 2 and immune regulatory responses, can both contribute toward the reduction in harmful type 1 immune responses that drive certain inflammatory diseases. Despite inducing type 2 responses, intestinal helminths may also downregulate harmful type 2 immune responses including allergic responses. We consider the possibility that intestinal helminth infection may indirectly affect inflammation by influencing the composition of the intestinal microbiome. Taken together, the studies reviewed herein suggest that intestinal helminth-induced responses have potent systemic effects on the immune system, raising the possibility that whole parasites or specific molecules produced by these metazoans may be an important resource for the development of future immunotherapies to control inflammatory diseases.

Initiation of the innate sterile inflammatory response that can develop in response to microparticle (MP) exposure is little understood. A potent type 2 immune response associated with accumulation of neutrophils, eosinophils, and alternatively activated (M2) macrophages was observed in response to sterile MPs similar in size to wear debris associated with prosthetic implants. Although elevations in IL-33 and type 2 cytokines occurred independently of Caspase-1 inflammasome signaling, the response was dependent on Bruton’s tyrosine kinase (BTK). IL-33 was produced by macrophages and BTK-dependent expression of IL-33 by macrophages was sufficient to initiate the type 2 response. Analysis of inflammation in patient periprosthetic tissue also revealed type 2 responses under aseptic conditions in patients undergoing revision surgery. These findings indicate for the that MP-induced sterile inflammation is initiated by macrophages activated to produce IL-33. They further suggest that both BTK and IL-33 may provide therapeutic targets for wear debris induced periprosthetic inflammation.

Highlights d Helminth-induced emphysema is IL-17-dependent and exacerbated in B cell-deficient mice d IL-4R signaling triggers activation of B cells that mitigate emphysematous pathology d These B cells express RELMa, which inhibits IL-17-producing gd T cells

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The determinants of helminth resistance are not well understood. In this issue of Cell Host & Microbe, Entwistle et al. (2017) provide intriguing evidence that a phospholipase A2 (Pla2gb1) produced by epithelial cells can impair larval development in helminths, providing a novel mechanism contributing to intestinal nematode resistance.

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Sterile solid microparticles (MPs) trigger an innate type 2 inflammatory response dependent on a SYK-BTK-IL33 signaling axis (Nature Materials,18, 289,2019). Inoculation with MPs trigger innate inflammation with influx of neutrophils, eosinophils and alternatively activated macrophages (M2). MPs also trigger cell death in macrophages leading to release of IL33 and the development of a type 2 response with increased IL4,IL5 and IL13 and expression of M2 markers including Arg1, Relmα and Chil3. Blockade of cell death by inhibiting necroptosis (necrox-2) or apoptosis (ZVED-FMK) alone or in combination inhibited the MP mediated release of IL33 by macrophages ex vivo. We also examined the role of adenosine in MP-mediated IL-33 release by inoculating LysMCreA2bfl/flwith MP.MP induced inflammation was blocked in LysMCreA2bfl/fmice compared to LysMCre controls, with significant decreases in type 2 cytokines and IL33. Adoptive transfer of wild type macrophages to LysMCreA2bfl/flrestored the MP-mediated type 2 inflammation. These findings indicate that programmed cell death and A2b receptor signaling pathways play a major role in particulate induced sterile inflammation.