Brachytherapy: An emblematic example of extreme hypofractionated regimen

In order to provide more convenient irradiation regimens for patient comfort, radiation facility organization and health expenses, new hypofractionated protocols have been evaluated. Moderately (dose/fraction: 2.3 to 3 Gy), then ultra (dose/fraction: 5.2 to 6.1 Gy) hypofractionated irradiations were first validated. The current question is: is it possible to go forward using extreme hypofractionated regimens (EHR) based on 1 to 3 fractions. Different irradiation techniques are under investigation. However, brachytherapy remains the smartest way to deliver a high dose in a small volume. We report prospective and retrospective study results which evaluated EHR for breast and prostate brachytherapy. While oncological outcome and toxicity profile appear extremely encouraging for low-risk breast cancer after a 1 to 4 fractions (6.25 to 20 Gy/fraction), the use of a single fraction of 19 to 23 Gy appears debatable for prostate cancer. Brachytherapy represents an emblematic example of EHR but longer follow-up and more mature results are awaited in order to specify the right indications and refine the EQD2 calculation method including new biological and technical factors.     

Effectiveness of a double-carbapenem combinations against carbapenem-resistant Gram-negative bacteria

The emergence of carbapenem-resistant organisms posed considerable threat to global health while only limited treatment options are available and led to efforts to discover a novel way to treat them. To evaluate in vitro synergistic activity of meropenem plus ertapenem, a total of 203 carbapenem-resistant strains, collected from 12 provinces and municipalities in China, were examined with a dual carbapenem combination therapy. The statistical software R was used for analysis. Two hundred and one (201) of carbapenem-resistant strains mainly produced four types of carbapenemase: KPC-2 (n = 142, 69.95%), OXA-232 (n = 7, 3.45%), NDM (n = 38, 18.72%; 36 NDM-1, 1 NDM-4, 1 NDM-5), and IMP (n = 15, 7.39%; 1 IMP-26, 10 IMP-30, 4 IMP-4). Fifty-one out of two hundred and three (51/203 or 25.12%) of the examined strains showed a synergistic effect for the meropenem plus ertapenem combination throughout the checkerboard method, while only three isolates showed potential clinically relevant synergy (3/203, 1.48%). An additive effect was observed in 55/203 (27.09%) of the examined strains. Ninety-seven of the examined isolates (47.78%) showed fractional inhibitory concentration (FIC) greater or equal to 2 (indicating antagonism). The synergistic activity of meropenem plus ertapenem combination suggests this combination can be a possible way to treat the infection caused by the carbapenem-resistant organisms, especially for IMP or NDM producer with a lesser minimum inhibitory concentration (MIC) and the infected individual who was not recommended to use colistin or tigecycline.     

EZH2对弥漫大B细胞淋巴瘤RCHOP方案治疗效果的预测价值

目的:探讨Zeste基因增强子(enhancer of zeste homolog 2,EZH2)对弥漫大B细胞淋巴瘤(diffuse large B-cell lymphoma,DLBCL)RCHOP方案治疗的效果的预测价值。方法:纳入2017年1月至2018年5月南华大学附属第二医院80例接受RCHOP方案治疗的DLBCL患者,分析患者EZH2表达情况与治疗效果的关系,绘制EZH2预测治疗效果的ROC曲线,并对患者pCR与病理特征的关系进行讨论。结果:80例患者中EZH2高表达者49例,EZH2低表达者31例,DLBCL患者RCHOP治疗的pCR率为51.25%,其中EZH2高表达患者完全缓解(complete response,CR)、客观缓解率(objective response rate,ORR)均明显低于EZH2低表达患者(P<0.05);EZH2预测治疗效果的曲线下面积为0.874(P<0.05);pCR与性别、年龄、美国东部肿瘤协作组(Eastern Cooperative Oncology Group,ECOG)得分、淋巴瘤国际预后指数(International Prognostic Index,IPI)得分、乳酸脱氢酶(lactate dehydrogenase,LDH)因素无相关关系(P>0.05);与Hans分型、EZH2表达水平存在一定的相关性(P<0.05)。结论:DLBCL患者EZH2低表达是RCHOP治疗后高pCR率的预测因子,在临床上有助于为DLBCL患者临床治疗提供更好的指导。     

Short-Duration Prednisolone in Children with Nephrotic Syndrome Relapse: A Noninferiority Randomized Controlled Trial

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Protocol for a pilot and feasibility study of nurse practitioner-pharmacist telehealth collaboration to simplify complex medication regimens

IntroductionNew and flexible multidisciplinary workforce models are needed to address unnecessary medication regimen complexity in residential aged care facilities (RACFs). This study will investigate the feasibility of a nurse practitioner-pharmacist telehealth-based collaborative care model to simplify complex medication regimens.MethodsThis is a pragmatic, non-randomized pilot and feasibility study of up to 30 permanent residents from 4 RACFs in Western Australia. Simplification will be conducted in accordance with a validated 5-step implicit process. Nurse practitioners will identify residents potentially interested in and who may benefit from simplification, including any regulatory or safety imperatives that might preclude simplification. Medication regimens will be assessed by an off-site clinical pharmacist to identify opportunities for simplification in terms of drug–drug, drug–food, or drug–time interactions, and the availability of alternative formulations. The pharmacist will communicate simplification opportunities to nurse practitioners via video case conferencing. Nurse practitioners will then discuss simplification opportunities with the resident, caregiver and the health and care team, including any unintended consequences for the resident or RACF. The primary outcome measure will be feasibility (stakeholder acceptability, protocol adherence, recruitment and retention rates). Secondary outcomes include change in the number of medication administration times per day, medication and behavioral incidents, falls and fractures, hospitalization and mortality at 4 months.Ethics and disseminationEthical approval has been obtained from the Monash University Human Research Ethics Committee. Research findings will be disseminated through industry report, lay summaries, conference presentations and peer-reviewed publications.     

Leukaemic variants of cutaneous T-cell lymphoma: Erythrodermic mycosis fungoides and Sézary syndrome

Mycosis fungoides (MF) and Sézary syndrome (SS) are the most common types of cutaneous lymphoma, accounting for approximately 60% of cutaneous T-cell lymphomas. Diagnosis requires correlation of clinical, histologic, and molecular features. A multitude of factors have been linked to the aetiopathogenesis, however, none have been definitively proven. Erythrodermic MF (E-MF) and SS share overlapping clinical features, such as erythroderma, but are differentiated on the degree of malignant blood involvement. While related, they are considered to be two distinct entities originating from different memory T cell subsets. Differential expression of PD-1 and KIR3DL2 may represent a tool for distinguishing MF and SS, as well as a means of monitoring treatment response. Treatment of E-MF/SS is guided by disease burden, patients’ ages and comorbidities, and effect on quality of life. Current treatment options include biologic, targeted, immunologic, and investigational therapies that can provide long term response with minimal side effects. Currently, allogeneic stem cell transplantation is the only potential curative treatment.     

Programmed Death 1 and Programmed Death Ligand 1 Inhibitors in Advanced and Recurrent Urothelial Carcinoma: Meta-analysis of Single-Agent Studies

We performed a systematic review and meta-analysis on the response rates of patients with treatment-refractory urothelial carcinoma treated with programmed cell death 1 (PD-1) and programmed death ligand 1 (PD-L1) inhibitors. We reviewed the literature for prospective studies evaluating PD-1/PD-L1 inhibitors in refractory urothelial carcinoma patients, which formed the basis for US Food and Drug Administration approval of 5 different antagonistic antibodies targeting PD-1 or PD-L1 (atezolizumab, durvalumab, avelumab, nivolumab, and pembrolizumab). We considered studies examining PD-1/PD-L1–treated patients, which we identified using the following key terms in the Pubmed, Scopus, Web of Science, ClinicalTrial.gov, and Cochrane Library databases. Eligible studies had ≥ 20 patients each and reported response rates, duration of response, and overall survival (OS). We performed fixed and random-effects meta-analyses to model the point estimates for objective response rate and complete response. The median progression-free survival (PFS) and OS for studies reporting these statistics were evaluated. We found 10 eligible studies that met our inclusion criteria, providing extractable numerators and denominators for response rates, PFS, and OS for 1934 patients with metastatic urothelial carcinoma. The objective response rate was 18% (95% confidence interval, 15-22) for second-line or later therapies. The random-effects estimate for complete response was 4% (95% confidence interval, 3-5), including all disease locations and all PD-1 and PD-L1 inhibitors. Median OS and PFS were < 13 months and 3 months, respectively, across all studies, irrespective of PD-L1 expression. We found that the estimated response rates of agents included in this meta-analysis seem to be more favorable than other salvage therapies.     

急诊治疗重症心力衰竭的方案及疗效探析

目的探讨急诊治疗重症心力衰竭的方案及疗效。方法选择本院80例2016年2月-2019年2月重症心力衰竭患者。随机分组,常规治疗组采取常规方法治疗,急诊治疗组则采取全面急诊治疗。比较两组重症心力衰竭疗效;重症心力衰竭症状改善的时间、心功能改善两级的时间;治疗前后患者舒张压、平均心率以及左心射血分数;不良反应。结果急诊治疗组重症心力衰竭疗效、重症心力衰竭症状改善的时间、心功能改善两级的时间、舒张压、平均心率以及左心射血分数相比较常规治疗组更好,P<0.05。两组未见严重不良反应,P>0.05。结论全面急诊治疗重症心力衰竭可获得较好预后,可有效改善患者的心功能,缓解症状,且安全性高,无明显不良反应。     

The future of bladder cancer therapy: Optimizing the inhibition of the fibroblast growth factor receptor

Therapeutic options for metastatic bladder cancer (BC) have seen minimal evolution over the past 30 years, with platinum-based chemotherapy remaining the mainstay of standard of care for metastatic BC. Recently, five immune checkpoint inhibitors (ICIs) have been approved by the FDA as second-line therapy, and two ICIs are approved as first-line treatment in selected patients. Molecular alterations of muscle-invasive bladder cancer (MIBC) have been reported by The Cancer Genome Atlas. About 15% of patients with MIBC have molecular alterations in the fibroblast growth factor (FGF) axis. Several ongoing trials are testing novel FGF receptor (FGFR) inhibitors in patients with FGFR genomic aberrations. Recently, erdafitinib, a pan-FGFR inhibitor, was approved by the FDA in patients with metastatic BC who have progressed on platinum-based chemotherapy. We reviewed the literature over the last decade and provide a summary of current knowledge of FGF signaling, and the prognosis associated with FGFR mutations in BC. We cover the role of FGFR inhibition with non-selective and selective tyrosine kinase inhibitors as well as novel agents in metastatic BC. Efficacy and safety data including insights from mechanism-based toxicity are reported for selected populations of metastatic BC with FGFR aberrations. Current strategies to managing resistance to anti-FGFR agents is addressed, and the importance of developing reliable biomarkers as the therapeutic landscape moves towards an individualized therapeutic approach.