Emergence of KRAS-mutation in liver metastases after an anti-EGFR treatment in patient with colorectal cancer: Are we aware of the therapeutic impact of intratumor heterogeneity?

Tumors represent a dynamic system where the genomic plasticity permits to adapt to the perturbation induced by environmental pressures, supporting the importance of longitudinal tumor sampling strategies to deciphering the temporal acquisition of driver event that could impact treatment outcome. We describe the case of a metastatic colorectal cancer (mCRC) patient, RAS wild-type, who responded to anti-EGFR therapy and underwent liver surgery, revealing a KRAS mutations in the metastatic lesion, not detectable prior to initiation of therapy in the colonic biopsy. After liver surgery, the patient received chemotherapy alone, then underwent left colectomy and the final pathological report confirmed the KRAS wild-type status. We can speculate the existence of two distinct populations of KRAS wild-type and mutant CRC cells sharing the same genetic origin. The anti-EGFR treatment represented a selective pressure which allowed the selection of KRAS mutant subclones. The prognostic and /or predictive role of intratumor heterogeneity has not been assessed prospectively. Our case report is of clinical relevance because patients with mCRC who respond to anti-EGFR antibodies often develop resistance within several months of initiating therapy, thus outlining the importance to better ascertain the molecular landscape of tumors to design better therapeutic strategies.     

小儿外科手术中行丙泊酚靶控加单次硬膜的效果探究

目的探究在小儿外科手术中行丙泊酚靶控加单次硬膜的效果。方法选取2012年9月-2014年1月来本院接受手术治疗的80例患儿作为研究对象，随机等分为研究组和对照组，分别为单次硬膜外加丙泊酚靶控和氯胺酮麻醉，比较不同时间段的两组患者血压、心率及血氧饱和度及肢体乱动、肌松程度等指标。结果对照组开始手术和结束手术时的血压、心率与进手术时前相比均显著升高（P〈0．05），而研究组的血压则无明显变化，但同时刻比较对照组则较低，差异有统计学意义（P〈0．05）；研究组心率在开始手术和结束手术时与进手术时前相比明显降低（P〈0．05），与对照组同时点相比也降低不少（P〈0．05）；研究组肢动较少，苏醒时间缩短，差别有统计学意义（P〈0．05）。结论在小儿外科手术中行丙泊酚靶控加单次硬膜对小儿呼吸、循环影响不大，并且有效果好、苏醒快、安全的特点。     

Precision Medicine in Myeloma: Challenges in Defining an Actionable Approach

Recently, large sequencing studies have provided insights into the mutational landscape of multiple myeloma (MM), identifying actionable mutations and giving a precious opportunity for exploring new targeted therapies. The main goal of precision medicine, matching patients with the right drug, seems to be closer than ever. However, no targeted therapies in MM are approved yet. Several clinical trials testing targeted drugs and enrolling patients with MM are currently ongoing and will provide predictive biomarkers that might support clinical decision making. In this review, we evaluate the evidence supporting the implementation of precision medicine in MM and we discuss the challenges that should be dealt with in this imminent and promising new era.     

Long term outcomes after bare metal stent implantation

Long term outcome data after BMS implant is not available from the Indian subcontinent. This is a prospective observational study which aims to study long term outcomes after BMS implant at a tertiary care centre. 100 consecutive patients underwent BMS implant and were followed up for 20 years. LAD was the most common vessel involved and different types of BMS were implanted. All-cause mortality was noted in 21% (n = 21) whereas cardiac mortality was seen in 16% (n = 16). Cumulative revascularisation free survival at 20 years was 71%. The study showed that long term outcomes after BMS implant were fare and acceptable.     

Individualized 3D-printed templates for high-dose-rate interstitial multicathether brachytherapy in patients with breast cancer

Purpose

High-dose-rate, multicatheter interstitial brachytherapy is technically complex and operator-dependent, requiring lengthy training and specialized skills. Furthermore, until the advent of contouring on computerized tomography (CT) images, difficulties existed in locating the target volume precisely. The present article reports the results of a study that aimed at producing and validating a 3D-printed template to aid in target volume localization for multicatheter interstitial brachytherapy in patients with breast cancer.

The relationship between the anteroposterior and mediolateral margins of stability in able-bodied human walking

BackgroundControl of dynamic balance in human walking is essential to remain stable and can be parameterized by the margins of stability. While frontal and sagittal plane margins of stability are often studied in parallel, they may covary, where increased stability in one plane could lead to decreased stability in the other. Hypothetically, this negative covariation may lead to critically low lateral stability during step lengthening.Research questionIs there a relationship between frontal and sagittal plane margins of stability in able-bodied humans, during normal walking and imposed step lengthening?MethodsFifteen able-bodied adults walked on an instrumented treadmill in a normal walking and a step lengthening condition. During step lengthening, stepping targets were projected onto the treadmill in front of the participant to impose longer step lengths. Covariation between frontal and sagittal plane margins of stability was assessed with linear mixed-effects models for normal walking and step lengthening separately.ResultsWe found a negative covariation between frontal and sagittal plane margins of stability during normal walking, but not during step lengthening.SignificanceThese results indicate that while a decrease in anterior instability may lead to a decrease in lateral stability during normal walking, able-bodied humans can prevent lateral instability due to this covariation in critical situations, such as step lengthening. These findings improve our understanding of adaptive dynamic balance control during walking in able-bodied humans and may be utilized in further research on gait stability in pathological and aging populations.