Charité

About: Charité is a healthcare organization based out in Berlin, Germany. It is known for research contribution in the topics: Population & Transplantation. The organization has 30624 authors who have published 64507 publications receiving 2437322 citations. The organization is also known as: Charite & Charité – University Medicine Berlin.

Eltrombopag for thrombocytopenia in patients with cirrhosis associated with hepatitis C.

Abstract: Background Eltrombopag is a new, orally active thrombopoietin-receptor agonist that stimulates thrombopoiesis. We evaluated its ability to increase platelet counts and facilitate treatment for hepatitis C virus (HCV) infection in patients with thrombocytopenia associated with HCV-related cirrhosis. Methods Seventy-four patients with HCV-related cirrhosis and platelet counts of 20,000 to less than 70,000 per cubic millimeter were randomly assigned to receive eltrombopag (30, 50, or 75 mg daily) or placebo daily for 4 weeks. The primary end point was a platelet count of 100,000 per cubic millimeter or more at week 4. Peginterferon and ribavirin could then be initiated, with continuation of eltrombopag or placebo for 12 additional weeks. Results At week 4, platelet counts were increased to 100,000 per cubic millimeter or more in a dose-dependent manner among patients for whom these data were available: in 0 of the 17 patients receiving placebo, in 9 of 12 (75%) receiving 30 mg of eltrombopag, in 15 of 19 (79...

What Safe Zone? The Vast Majority of Dislocated THAs Are Within the Lewinnek Safe Zone for Acetabular Component Position.

Abstract: Numerous factors influence total hip arthroplasty (THA) stability including surgical approach and soft tissue tension, patient compliance, and component position. One long-held tenet regarding component position is that cup inclination and anteversion of 40° ± 10° and 15° ± 10°, respectively, represent a “safe zone” as defined by Lewinnek that minimizes dislocation after primary THA; however, it is clear that components positioned in this zone can and do dislocate. We sought to determine if these classic radiographic targets for cup inclination and anteversion accurately predicted a safe zone limiting dislocation in a contemporary THA practice. From a cohort of 9784 primary THAs performed between 2003 and 2012 at one institution, we retrospectively identified 206 THAs (2%) that subsequently dislocated. Radiographic parameters including inclination, anteversion, center of rotation, and limb length discrepancy were analyzed. Mean followup was 27 months (range, 0–133 months). The majority (58% [120 of 206]) of dislocated THAs had a socket within the Lewinnek safe zone. Mean cup inclination was 44° ± 8° with 84% within the safe zone for inclination. Mean anteversion was 15° ± 9° with 69% within the safe zone for anteversion. Sixty-five percent of dislocated THAs that were performed through a posterior approach had an acetabular component within the combined acetabular safe zones, whereas this was true for only 33% performed through an anterolateral approach. An acetabular component performed through a posterior approach was three times as likely to be within the combined acetabular safe zones (odds ratio [OR], 1.3; 95% confidence interval [CI], 1.1–1.6) than after an anterolateral approach (OR, 0.4; 95% CI, 0.2–0.7; p < 0.0001). In contrast, acetabular components performed through a posterior approach (OR, 1.6; 95% CI, 1.2–1.9) had an increased risk of dislocation compared with those performed through an anterolateral approach (OR, 0.8; 95% CI, 0.7–0.9; p < 0.0001). The historical target values for cup inclination and anteversion may be useful but should not be considered a safe zone given that the majority of these contemporary THAs that dislocated were within those target values. Stability is likely multifactorial; the ideal cup position for some patients may lie outside the Lewinnek safe zone and more advanced analysis is required to identify the right target in that subgroup. Level III, therapeutic study.

Immunosuppressive plasma cells impede T-cell-dependent immunogenic chemotherapy.

Abstract: Cancer-associated genetic alterations induce expression of tumour antigens that can activate CD8(+) cytotoxic T cells (CTLs), but the microenvironment of established tumours promotes immune tolerance through poorly understood mechanisms. Recently developed therapeutics that overcome tolerogenic mechanisms activate tumour-directed CTLs and are effective in some human cancers. Immune mechanisms also affect treatment outcome, and certain chemotherapeutic drugs stimulate cancer-specific immune responses by inducing immunogenic cell death and other effector mechanisms. Our previous studies revealed that B cells recruited by the chemokine CXCL13 into prostate cancer tumours promote the progression of castrate-resistant prostate cancer by producing lymphotoxin, which activates an IκB kinase α (IKKα)-BMI1 module in prostate cancer stem cells. Because castrate-resistant prostate cancer is refractory to most therapies, we examined B cell involvement in the acquisition of chemotherapy resistance. Here we focus on oxaliplatin, an immunogenic chemotherapeutic agent that is effective in aggressive prostate cancer. We show that mouse B cells modulate the response to low-dose oxaliplatin, which promotes tumour-directed CTL activation by inducing immunogenic cell death. Three different mouse prostate cancer models were refractory to oxaliplatin unless genetically or pharmacologically depleted of B cells. The crucial immunosuppressive B cells are plasmocytes that express IgA, interleukin (IL)-10 and programmed death ligand 1 (PD-L1), the appearance of which depends on TGFβ receptor signalling. Elimination of these cells, which also infiltrate human-therapy-resistant prostate cancer, allows CTL-dependent eradication of oxaliplatin-treated tumours.