Effects of tamoxifen on normal breast tissue histological composition: Results from a randomised six-arm placebo-controlled trial in healthy women

Tamoxifen prevents recurrence of breast cancer and is suggested for preventive risk-reducing therapy. Tamoxifen reduces mammographic density, a proxy for therapy response, but little is known about its effects in remodelling normal breast tissue. Our study, a substudy within the double-blinded dose-determination trial KARISMA, investigated tamoxifen-specific changes in breast tissue composition and histological markers in healthy women. We included 83 healthy women randomised to 6 months daily intake of 20, 10, 5, 2.5, 1 mg of tamoxifen or placebo. The groups were combined to “no dose” (0-1 mg), “low-dose” (2.5-5 mg) or “high-dose” (10-20 mg) of tamoxifen. Ultrasound-guided biopsies were collected before and after tamoxifen exposure. In each biopsy, epithelial, stromal and adipose tissues was quantified, and expression of epithelial and stromal Ki67, oestrogen receptor (ER) and progesterone receptor (PR) analysed. Mammographic density using STRATUS was measured at baseline and end-of-tamoxifen-exposure. We found that different doses of tamoxifen reduced mammographic density and glandular-epithelial area in premenopausal women and associated with reduced epithelium and increased adipose tissue. High-dose tamoxifen also decreased epithelial ER and PR expressions in premenopausal women. Premenopausal women with the greatest reduction in proliferation also had the greatest epithelial reduction. In postmenopausal women, high-dose tamoxifen decreased the epithelial area with no measurable density decrease. Tamoxifen at both low and high doses influences breast tissue composition and expression of histological markers in the normal breast. Our findings connect epithelial proliferation with tissue remodelling in premenopausal women and provide novel insights to understanding biological mechanisms of primary prevention with tamoxifen.     

Fragmentation of care as a barrier to optimal ESKD management

Caring for patients with end-stage kidney disease (ESKD) in the United States is challenging, due in part to the complex epidemiology of the disease's progression as well as the ways in which care is delivered. As CKD progresses toward ESKD, the number of comorbidities increases and care involves multiple healthcare providers from multiple subspecialties. This occurs in the context of a fragmented US healthcare delivery system that is traditionally siloed by provider specialty, organization, as well as systems of payment and administration. This article describes the role of care fragmentation in the delivery of optimal ESKD care and identifies research gaps in the evidence across the continuum of care. We then consider the impact of care fragmentation on ESKD care from the patient and health system perspectives and explore opportunities for system-level interventions aimed at improving care for patients with ESKD.     

Mixed Reality Combined with Three‐Dimensional Printing Technology in Total Hip Arthroplasty: An Updated Review with a Preliminary Case Presentation

Three‐dimensional (3D) printing technology, virtual reality, and augmented reality technology have been used to help surgeons to complete complex total hip arthroplasty, while their respective shortcomings limit their further application. With the development of technology, mixed reality (MR) technology has been applied to improve the success rate of complicated hip arthroplasty because of its unique advantages. We presented a case of a 59‐year‐old man with an intertrochanteric fracture in the left femur, who had received a prior left hip fusion. After admission to our hospital, a left total hip arthroplasty was performed on the patient using a combination of MR technology and 3D printing technology. Before surgery, 3D reconstruction of a certain bony landmark exposed in the surgical area was first performed. Then a veneer part was designed according to the bony landmark and connected to a reference registration landmark outside the body through a connecting rod. After that, the series of parts were made into a holistic reference registration instrument using 3D printing technology, and the patient's data for bone and surrounding tissue, along with digital 3D information of the reference registration instrument, were imported into the head‐mounted display (HMD). During the operation, the disinfected reference registration instrument was installed on the selected bony landmark, and then the automatic real‐time registration was realized by HMD through recognizing the registration landmark on the reference registration instrument, whereby the patient's virtual bone and other anatomical structures were quickly and accurately superimposed on the real body of the patient. To the best of our knowledge, this is the first report to use MR combined with 3D printing technology in total hip arthroplasty.     

不同波形低频率电刺激对小鼠海马电点燃癫痫的作用比较

目的观察比较不同脉冲波形的低频率电刺激对海马电点燃癫痫模型小鼠的作用差异。方法采用电点燃刺激法建立小鼠癫痫模型, 观察正弦波、单相方波、双相方波低频率电刺激对模型小鼠癫痫行为发作及后放电持续时间的影响, 并比较不同时间点给予正弦波低频率电刺激的抗癫痫作用。结果与对照组比较, 正弦波低频率电刺激30 s能降低小鼠海马电点燃癫痫发作等级(2.85 ± 0.27 vs 4.75 ±0.12, P < 0.05)、减少大发作概率(53.6% vs 96.5%, P < 0.01) 和缩短后放电持续时间[(16.22 ± 1.69) s vs (30.29 ± 1.12) s, P < 0.01], 而单相方波和双相方波低频率电刺激30 s没有明显的抗癫痫作用。常用的单相方波低频率电刺激15 min能降低小鼠海马电点燃发作等级(3.58 ± 0.16, P < 0.05)、减少大发作概率(66.7%, P < 0.01);但对海马后放电持续时间及大发作持续时间无影响(均 P>0.05)。此外, 电点燃刺激前预先给予或结束后3 s内给予正弦波低频率电刺激具有明显的抗癫痫作用( P < 0.05或 P < 0.01), 而电点燃刺激结束10 s给予正弦波低频率电刺激则无上述抗癫痫作用。 结论低频率电刺激抗癫痫作用受波形参数的影响, 其中正弦波低频率电刺激能有效抑制小鼠海马电点燃癫痫的发作。     

Radiation dose reduction in CT-guided cryoablation of renal tumors

PURPOSEWe aimed to evaluate the effect on the radiation dose to the patient by reducing the tube current during the placement of the ablation needles (reduced dose group) compared with the patient doses delivered when scanning at the standard fully diagnostic level (full dose group) in computed tomography (CT)-guided percutaneous cryoablation.METHODSWe conducted a retrospective study of 103 patients undergoing cryoablation in a tertiary cancer center. Overall, 62 patients were scanned with standard exposure parameters (full dose group) set on a 64-slice multidetector CT scanner, while 41 patients were scanned on a reduced dose protocol. Dose levels were retrieved from the hospital picture and archiving communication system including the volumetric CT dose index (CTDIvol), total dose length product (DLP), length of cryoablation procedure, number of cryoablation needles and patient size. Wilcoxon Mann-Whitney (rank-sum) tests were used to compare the median DLP, CTDIvol and skin dose between the two groups.RESULTSMedian total DLP for the full dose group was 6025 mGy·cm (1909–13353 mGy·cm) compared with 3391 mGy·cm (1683–6820 mGy·cm) for the reduced dose group. The reduced dose group had a 44% reduction in total DLP and 42% reduction in total CTDIvol (p < 0.001). The estimated skin doses were 384 mGy for the full dose group and 224 mGy for the reduced dose group (42% reduction) (p < 0.001). At 12-month follow-up, the technical success for the full dose (n=62) was 97% with 2 patients requiring a further cryoablation treatment for residual tumor. The technical success for the reduced dose group (n=41) was 100%.CONCLUSIONCT dose reduction technique during image-guided cryoablation treatment of renal tumors can achieve significant radiation dose reduction whilst maintaining sufficient image quality.

Renal cell carcinoma is the most common kidney cancer and has a rising incidence (1–4), with obesity and smoking being major risk factors (5–8).Image-guided ablation offers a more minimally invasive option compared with surgery and the current evidence base shows that it is a safe and effective treatment for T1a tumors, with a low rate of complications (9–11). The major advantage of cryoablation over other modalities is the ability to accurately visualize the iceball and therefore zone of ablation on intraprocedural imaging, either with computed tomography (CT) or magnetic resonance imaging (MRI) (12, 13). However, renal cryoablation involves the placement of more ablation probes and can have almost three times the radiation exposure compared with CT-guided radiofrequency ablation procedures (14).In addition to this substantial radiation dose per cryoablation, estimated to be between 32 and 39.7 mSv, the follow-up CT imaging will also add to the total radiation burden (15, 16). Whilst this level of radiation dose and associated stochastic risk may be a lesser concern in the older patients, greater consideration needs to be given to younger patients (<50 years old) and in patients requiring lifelong follow-up imaging, in particular those with hereditary diseases such as Von Hippel-Lindau syndrome (15). To our knowledge, the potential for reducing radiation dose for cryoablation patients.The principle aim of this study was to evaluate the effect on the radiation dose to the patient by reducing the tube current during the placement of the ablation needles (reduced dose group) compared with the patient doses delivered when scanning at the standard fully diagnostic level (full dose group) in CT-guided percutaneous cryoablation.