Efficacy and Safety of Atezolizumab Plus Bevacizumab Following Disease Progression on Atezolizumab or Sunitinib Monotherapy in Patients with Metastatic Renal Cell Carcinoma in IMmotion150: A Randomized Phase 2 Clinical Trial

BackgroundThe use of immune checkpoint inhibitors combined with vascular endothelial growth factor (VEGF)-targeted therapy as second-line treatment for metastatic clear cell renal cancer (mRCC) has not been evaluated prospectively.ObjectiveTo evaluate the efficacy and safety of atezolizumab + bevacizumab following disease progression on atezolizumab or sunitinib monotherapy in patients with mRCC.Design, setting, and participantsIMmotion150 was a multicenter, randomized, open-label, phase 2 study of patients with untreated mRCC. Patients randomized to the atezolizumab or sunitinib arm who had investigator-assessed progression as per RECIST 1.1 could be treated with second-line atezolizumab + bevacizumab.InterventionPatients received atezolizumab 1200 mg intravenously (IV) plus bevacizumab 15 mg/kg IV every 3 wk following disease progression on either atezolizumab or sunitinib monotherapy.Outcome measurements and statistical analysisThe secondary endpoints analyzed during the second-line part of IMmotion150 included objective response rate (ORR), progression-free survival (PFS), and safety. PFS was examined using Kaplan-Meier methods.Results and limitationsFifty-nine patients in the atezolizumab arm and 78 in the sunitinib arm were eligible, and 103 initiated second-line atezolizumab + bevacizumab (atezolizumab arm, n = 44; sunitinib arm, n = 59). ORR (95% confidence interval [CI]) was 27% (19–37%). The median PFS (95% CI) from the start of second line was 8.7 (5.6–13.7) mo. The median event follow-up duration was 19.4 (12.9–21.9) mo among the 25 patients without a PFS event. Eighty-six (83%) patients had treatment-related adverse events; 31 of 103 (30%) had grade 3/4 events. Limitations were the small sample size and selection for progressors.ConclusionsThe atezolizumab + bevacizumab combination had activity and was tolerable in patients with progression on atezolizumab or sunitinib. Further studies are needed to investigate sequencing strategies in mRCC.Patient summaryPatients with advanced kidney cancer whose disease had worsened during treatment with atezolizumab or sunitinib began second-line treatment with atezolizumab + bevacizumab. Tumors shrank in more than one-quarter of patients treated with this combination, and side effects were manageable.     

Assessment of the Long-Term Impact of Pancreatoduodenectomy on Health-Related Quality of Life Using the EORTC QLQ-PAN26 Module

Annals of Surgical Oncology - Long-term pancreatoduodenectomy (PD) survivors have previously reported favorable quality of life (QoL). However, there has been a paucity of studies utilizing...     

尿毒症患者急性缺氧状态下血清红细胞生成素浓度的变化

７例尿毒症贫血患者在自发急性缺氧状态下，其血清红细胞生成素（ＥＰＯ）浓度显著提高（平均７倍），且与ＰＯ２呈负相关。缺氧状态纠正后血清ＥＰＯ浓度下降。提示尿毒症贫血患者的ＥＰＯ氧依赖调控系统功能尚存在，但处于不敏感的低调状态。进一步了解其机遇，则可能通过促进内源性ＥＰＯ的生成，有助于悄毒症贫血的治疗。     

Differential expression of FMR1, FXR1 and FXR2 proteins in human brain and testis

Lack of expression of the fragile X mental retardation protein (FMRP) results in mental retardation and macroorchidism, seen as the major pathological symptoms in fragile X patients. FMRP is a cytoplasmic RNA- binding protein which cosediments with the 60S ribosomal subunit. Recently, two proteins homologous to FMRP were discovered: FXR1 and FXR2. These novel proteins interact with FMRP and with each other and they are also associated with the 60S ribosomal subunit. Here, we studied the expression pattern of the three proteins in brain and testis by immunohistochemistry. In adult brain, FMR1, FXR1 and FXR2 proteins are coexpressed in the cytoplasm of specific differentiated neurons only. However, we observed a different expression pattern in fetal brain as well as in adult and fetal testis, suggesting independent functions for the three proteins in those tissues during embryonic development and adult life.      

Investigation of nimodipine pharmacokinetics in Chinese patients with acute subarachnoid haemorrhage

Summary Nimodipine pharmacokinetics was investigated in 12 Chinese patients with acute subarachnoid haemorrhage receiving an IV infusion of 1.6 or 2 mg/h (based on estimated body weight) for 10 days. Peripheral venous blood samples were collected for up to 4 days and plasma nimodipine was assayed by GC/ECD. The mean value was taken as the steady state concentration (C_ss) and Clearance (CL) (hourly dose/C_ss) was calculated. Eight survivors were given oral nimodipine (60 or 90 mg) every 6h (based on body weight), blood was sampled over 6 h and the plasma nimodipine level determined. The values for C_ss, CL and CL·kg^–1 were 33.5 g·l^–1, 58 l·h^–1 and 1.0 l·h^–1·kg^–1 respectively; in survivors receiving the drug orally, bioavailability of the 30 mg tablet was 9%. In one very sick patient given crushed tablets by naso-gastric tube, the AUC was very low; in vitro studies indicated that adsorption of nimodipine by the tubing was unlikely to have been the cause.The pharmacokinetic findings in Chinese patients are comparable to previously reported values in Caucasians.     

Immunohistochemical diagnosis in fine-needle aspiration cytology

This paper reports 25 kinds of polyclonal or monoclonal antibodies by ABC immunohistochemical technique used for 253 cell smears by fine-needle aspiration. The results were,1. Immunohistochemical diagnosis were classified into 136 metastatic cancers ( K12 EMA CEA LCA-),92 lymphomas (LCA k12- EMA- CEA-), 4 mesenchymal tumors (Vimentin ), 3 melanomas (S-100 NSE ). 15 reactive proliferations (k λ4 CD CD8 ) and 3 unspecified.2. The origin of 70 metastatic cancers were classified into 36 lung (HLC3-AB ), 4 gastrointestinal tract (MG7 ), 8 thyroid (TGB ), 1 prostate (PSA ), 3 liver (AFP ) and 14 unknown. 3. Immunologic phenotype of 87 lymphomas wereclassified into 66 cases of B-cell, 4 T-cell, 3 hsitocyte, 7 Hodgkin' s diseases and 7 unclear. The above results suggest that immunohistochemlcal method may be used as a new method of diagnosing and differentiating epithelial and non-epithelial tumors, detecting primary focus of metastatic cncer, differentiating between reactive proliferation adn lymphome a