Differential Ly6C Expression after Renal Ischemia-Reperfusion Identifies Unique Macrophage Populations

Macrophages are a heterogeneous cell type implicated in injury, repair, and fibrosis after AKI, but the macrophage population associated with each phase is unclear. In this study, we used a renal bilateral ischemia-reperfusion injury mouse model to identify unique monocyte/macrophage populations by differential expression of Ly6C in CD11b⁺ cells and to define the function of these cells in the pathophysiology of disease on the basis of microarray gene signatures and reduction strategies. Macrophage populations were isolated from kidney homogenates by fluorescence-activated cell sorting for whole genome microarray analysis. The CD11b⁺/Ly6C^high population associated with the onset of renal injury and increase in proinflammatory cytokines, whereas the CD11b⁺/Ly6C^intermediate population peaked during kidney repair. The CD11b⁺/Ly6C^low population emerged with developing renal fibrosis. Principal component and hierarchical cluster analyses identified gene signatures unique to each population. The CD11b⁺/Ly6C^intermediate population had a distinct phenotype of wound healing, confirmed by results of studies inhibiting the macrophage colony-stimulating factor 1 receptor,whereas the CD11b⁺/Ly6C^low population had a profibrotic phenotype. All populations, including the CD11b⁺/Ly6C^high population, carried differential inflammatory signatures. The expression of M2-specific markers was detected in both the CD11b⁺/Ly6C^intermediate and CD11b⁺/Ly6C^low populations, suggesting these in vivo populations do not fit into the traditional classifications defined by in vitro systems. Results of this study in a renal ischemia-reperfusion injury model allow phenotype and function to be assigned to CD11b⁺/Ly6C⁺ monocyte/macrophage populations in the pathophysiology of disease after AKI.     

Impact of Family History of Substance Abuse on Admission Opioid Dose,Depressive Symptoms,and Pain Catastrophizing in Patients with Chronic Pain

The objectives of this study were to examine association between a family history of substance abuse and admission morphine equivalent dose, depression and pain catastrophizing screening scores, as well as reported personal history of substance use. The retrospective research was completed in an interdisciplinary three-week pain rehabilitation center. The subject cohort included admissions from January through December 2014 with 351 datasets for family history of substance abuse and oral morphine equivalency and 341 for depression, pain catastrophizing and use of substances. Outcome measures included admission self-reported data on family history of substance abuse and past and current substance use, admission morphine equivalency dose, and scores on the Center for Epidemiologic Studies-Depression Scale and the Pain Catastrophizing Scale. One hundred forty-seven patients were using opioid medications on admission and those with a positive family history of substance abuse had an oral morphine equivalency (M = 92.12, SD = 95.32) compared to a negative history (M = 80.34, SD = 64.86); the difference was not statistically significant, t (120.01) =.87, p = .39. Patients with a positive family history reported higher levels of both depression, t (327.40) = 3.15, p = .002 and pain catastrophizing, t (338) = 2.76, p = .01. Those with a positive family history endorsed greater frequency of past alcohol use χ² (1, N = 326) = 6.67, p = 0.1 and marijuana use χ² (1, N = 341) = 4.23, p = .04 and past χ² (1, N = 329) = 9.90, p = .002 and current tobacco use χ² (1, N = 327) = 8.81, p = .003. Use of family history of substance abuse information may help provide data for multimodal treatments of chronic non-cancer-pain. The findings from this study can be used to guide future research.     

Safety of rush immunotherapy using a modified schedule: a cumulative experience of 893 patients receiving multiple aeroallergens.

Conventional immunotherapy (IT) is effective in treating allergic rhinitis, allergic asthma, and chronic rhinosinusitis. Disadvantages include poor compliance, delayed efficacy, and patient frustration. Rush IT, or rapid desensitization, offers the advantages of rapid response, improved compliance, and cost-effectiveness. Although premedication with corticosteroids and antihistamines dramatically reduces systemic reactions, safety remains a primary concern. Two separate half-day schedules with minor differences were used to rapidly desensitize 893 patients (aged 1.5-77 years) in two typical outpatient settings equipped to treat anaphylaxis. All patients exhibited positive skin-prick tests to perennial and seasonal allergens. Diagnoses included allergic rhinitis (857/96%), allergic asthma (505/57%), and chronic rhinosinusitis (384/43%). Five hundred sixty-eight patients were premedicated with prednisone and HI-antihistamine for 3 days. Three hundred twenty-five patients were premedicated for 3 days with prednisone and H1- and H2-blockade. The protocol's final dose ranged from 0.1 to 0.5 mL of a 1:1000 dilution of extracts manufactured by ALK and Greer Laboratories. Patients continued on to higher doses by resuming a conventional schedule. Eighteen patients (2.0%) experienced a mild systemic reaction. All responded to subcutaneous epinephrine and/or nebulized albuterol and were sent home after observation. One patient (0.1%) experienced true anaphylaxis and received appropriate treatment and observation. Our experience with rush IT confirms that maintenance IT can be reached quickly and safely under careful supervision. Caution must be exercised when using this procedure because anaphylaxis does occur. Systemic reactions occur less frequently using a lower targeted final dose than previously described in the literature.     

Lympho- and myeloproliferative disorders in renal transplant recipients--one center's experience and review of the literature

Recipients of renal transplants have an increased risk of developing secondary malignancies. About 4% of patients who underwent kidney transplantation will develop cancer, and 1% of transplanted patients will develop lymphoproliferative disorders. According to clinical analyses and laboratory data, the main reason for increased risk of developing malignant disease in this group of patients, is their immunocompromised status due to immunosuppressive treatment. So called "strong" immunosuppressive drugs like antilymphocytic globulin (ALG), antithymocytic globulin (ATG), or monoclonal globulin OKT3 seem to favor the development of secondary malignancies much more than other drugs, like: corticosteroids, azathioprine (AZA), or cyclosporine (CsA). Secondary lymphoproliferative disorders are usually connected with reactivation of Ebstein-Barr virus infection. Patients with early onset (<1 year after the transplantation) have a favorable clinical course after withdrawal of immunosuppression. The subset of late-onset (>1 year) has usually much more aggressive clinical course and patients require intensive treatment. The general recommendation in these patients is to stop or to reduce the immunosuppressive treatment and to continue the chemotherapy in full dose. This treatment is often complicated by severe infections, but it offers a chance to achieve remission without worsening the function of transplanted organ. In this paper we are presenting five patients with secondary lympho- or myeloproliferative disorders after kidney transplantation and give an overview of the recent literature in this field.