Phase I and pharmacokinetic study of veliparib,a PARP inhibitor,and pegylated liposomal doxorubicin (PLD) in recurrent gynecologic cancer and triple negative breast cancer with long-term follow-up

Poly(ADP-ribosyl) polymerases (PARPs) are nuclear enzymes with roles in DNA damage recognition and repair. PARP1 inhibition enhances the effects of DNA-damaging agents like doxorubicin. We sought to determine the recommended phase two dose (RP2D) of veliparib with pegylated liposomal doxorubicin (PLD) in breast and recurrent gynecologic cancer patients. Veliparib and PLD were administered in a standard phase 1, 3 + 3 dose-escalation design starting at 50 mg veliparib BID on days 1–14 with PLD 40 mg/mg2 on day 1 of a 28-day cycle. Dose escalation proceeded in two strata: A (prior PLD exposure) and B (no prior PLD exposure). Patients underwent limited pharmacokinetic (PK) sampling; an expansion PK cohort was added. 44 patients with recurrent ovarian or triple negative breast cancer were enrolled. Median age 56 years; 23 patients BRCA mutation carriers; median prior regimens four. Patients received a median of four cycles of veliparib/PLD. Grade 3/4 toxicities were observed in 10% of patients. Antitumor activity was observed in both sporadic and BRCA-deficient cancers. Two BRCA mutation carriers had complete responses. Two BRCA patients developed oral squamous cell cancers after completing this regimen. PLD exposure was observed to be higher when veliparib doses were > 200 mg BID. The RP2D is 200 mg veliparib BID on days 1–14 with 40 mg/m2 PLD on day 1 of a 28-day cycle. Anti-tumor activity was seen in both strata. However, given development of long-term squamous cell cancers and the PK interaction observed, efforts should focus on other targeted combinations to improve efficacy.     

Rosmarinus plants: Key farm concepts towards food applications

Rosmarinus species are aromatic plants that mainly grow in the Mediterranean region. They are widely used in folk medicine, food, and flavor industries and represent a valuable source of biologically active compounds (e.g., terpenoids, flavonoids, and phenolic acids). The extraction of rosemary essential oil is being done using three main methods: carbon dioxide supercritical extraction, steam distillation, and hydrodistillation. Furthermore, interesting antioxidant, antibacterial, antifungal, antileishmanial, anthelmintic, anticancer, anti‐inflammatory, antidepressant, and antiamnesic effects have also been broadly recognized for rosemary plant extracts. Thus the present review summarized data on economically important Rosmarinus officinalis species, including isolation, extraction techniques, chemical composition, pharmaceutical, and food applications.     

不同病理分级的胰腺神经内分泌肿瘤的MRI征象对比分析及“主胰管绕道征”的诊断价值探讨

目的:对比分析G1、G2级胰腺神经内分泌肿瘤（pNEN）的MRI征象，探讨“主胰管绕道征”的诊断价值。方法:收集32例pNEN患者的临床资料，以术后病理学检查为金标准，定量分析G1、G2级临床指标及影像学指标的差异，并着重分析pNEN与主胰管的关系。结果:32例患者中，病理分级G1、G2、G3级的患者分别有12例、16例、4例，分别以胰尾、胰头、胰颈为主要发生部位。与G1级神经内分泌瘤（NET）相比，G2级NET肿瘤直径显著增大，不规则形态的病灶增多，边缘模糊，生物学行为出现明显恶性倾向，主胰管扩张、胰腺外侵犯及淋巴结/肝转移的发生率升高。G1级NET的MRI平扫信号均质程度高于G2级（P＜0.05），但二者在增强MRI扫描的各个期象信号强度均无明显差异（P＞0.05）。28例NET患者中，22例（78.6%）出现主胰管绕道征；神经内分泌癌（NEC）患者无一例出现此征象。术前，28例NET的诊断准确率为78.6%（22/28），存在6例误诊，其中，3例误诊为胰腺癌，2例误诊为囊腺瘤（癌），1例误诊为胰腺假性囊肿。在原MRI诊断依据的基础上纳入“主胰管绕道征”，诊断准确率提高至89.3%（25/28），但仍存在3例误诊，其中2例误诊为囊腺瘤（癌），1例误诊为胰腺假性囊肿，排除了胰腺癌的误诊。结论:MRI对鉴别诊断良恶性pNEN有较高的准确性，但对部分G1与G2级NET仍存在一定的误诊率，主胰管绕道征可帮助减少出现胰腺癌误诊。     

One Week of Hospitalization Following Elective Hip Surgery Induces Substantial Muscle Atrophy in Older Patients

Objectives

Short successive periods of skeletal muscle disuse have been suggested to substantially contribute to the observed loss of skeletal muscle mass over the life span. Hospitalization of older individuals due to acute illness, injury, or major surgery generally results in a mean hospital stay of 5 to 7 days, during which the level of physical activity is strongly reduced. We hypothesized that hospitalization following elective total hip arthroplasty is accompanied by substantial leg muscle atrophy in older men and women.

A prospective,double-blind,randomized, placebo-controlled study on the efficacy and safety of influenza vaccination in myasthenia gravis

Objective

To investigate the efficacy and safety of an influenza vaccination in patients with myasthenia gravis with acetylcholine receptor antibodies (AChR MG).

Radiothérapie en conditions stéréotaxiques : étude prospective évaluant la fatigue et la qualité de vie

PurposeTo evaluate prospectively asthenia and the quality of life in patients treated by stereotactic body irradiation and to determine their predictive factors.Methods and materialsQuality of life was assessed by the EORTC QLQ-C30 and asthenia was evaluated with the Brief Fatigue Inventory (BFI), on the first day (T1), last day (T2) and 1–3 weeks after the end of treatment (T3).ResultsSixty-three patients were treated with stereotactic body irradiation from February 2017 to May 2017 and 41 were included in the analysis (22 patients excluded for lack of understanding, organization, psychologic disorders or refusal). The mean number of fractions was 5 (± 2). The compliance to quality of life assessment was 98%, 95% was 81% at T1, T2 and T3, respectively. An increase of asthenia and a worsened quality of life were found in 12 (29%) and 14 (34%) patients between T1 and T2. Univariate analysis demonstrated a correlation between asthenia and quality of life were correlated with performans status (P = 0.03 and 0.05 respectively), hemoglobin level (p = 0.01 and 0.004), albumin level (P = 0.01 and 0.06), distance between home and radiotherapy department (P = 0.05 and 0.02). Multivariate analysis demonstrated a correlation between female gender (P = 0.012), albumin level (P < 0.001), distance over 25 km (P < 0.001) with asthenia, and albumin level (P = 0.003), hemoglobin level (P = 0.004) and previous chemotherapy (P = 0.003) with quality of life. No influence of stereotactic body ratiotherapy parameters was seen.ConclusionDespite hypofractionation, stereotactic body radiotherapy induced asthenia and deterioration of quality of life.