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.     

Prospective characterization of incident hepatic steatosis in pediatric and adolescent patients after total pancreatectomy with islet autotransplantation

BackgroundHepatic steatosis has been described as a common finding in adults following total pancreatectomy with islet autotransplantation (TPIAT) but it is unknown if this occurs in children and adolescents.ObjectivesTo define the frequency of post-TPIAT hepatic steatosis in a sample of children and adolescents and to identify clinical predictors of incident steatosis post-TPIAT.MethodsIn this prospective study, consecutive participants at least 1-month post-TPIAT underwent a liver MRI with proton density fat fraction (PDFF) and blood draw at our pediatric academic medical center between April 2021 and January 2022. Comparison clinical pre-TPIAT liver MRI or ultrasound and insulin use and graft function data were extracted from the medical record. T-tests were used for the comparison of means across continuous variables between participants with and without post-TPIAT steatosis.ResultsA total of 20 participants (mean: 13 ± 4 years; 12 female) were evaluated. Mean liver PDFF at research MRI was 7.4 ± 6.2% (range: 2–25%). Seven participants (35%) had categorical hepatic steatosis (PDFF>5%) post-TPIAT, five of whom had pre-TPIAT steatosis, reflecting a 13% (2/15; 95% CI: 2–40%) incidence of post-TPIAT steatosis. Participant characteristics were not significantly different between subgroups with and without post-TPIAT steatosis. Mean PDFF at research MRI was not different between graft function subgroups (7.5% optimal/good vs. 7.3% marginal/failure; p = .96).ConclusionOur study shows a moderate prevalence but low incidence of hepatic steatosis in a small sample of children and adolescents post-TPIAT. This study raises questions about a causal relationship between TPIAT and hepatic steatosis.     

中低度近视FS-LASIK、SMILE及ICL植入术的效果比较

目的比较飞秒激光制瓣准分子激光原位角膜磨镶术(FS-LASIK)、全飞秒激光小切口角膜基质透镜取出术(SMILE)和有晶状体眼后房型人工晶状体(ICL V4c)植入术三者矫正中低度近视的效果。方法采用回顾性研究。以惠州爱尔眼科医院2019年6月至2020年4月矫正中低度近视120例(120眼)作为研究对象,受术者分为FS-LASIK组、SMILE组及ICL组,每组40例(40眼),各组分别接受相应的手术,术后随访3个月比较其矫正效果。结果术后1个月及3个月,3组间视力及有效性指数对比差异无统计学意义(P>0.05);ICL组安全性指数高于SMILE组及FS-LASIK组(P<0.05)。术后3个月FS-LASIK组的三叶草像差、彗差和球差出现明显变化,而SMILE组的变化较小,ICL组变化最小(P<0.05)。结论对中低度近视FS-LASK、SMILE及ICL植入术三者均有确切疗效,而ICL V4c植入术的安全性最高,患者的视觉质量最好。     

OCT及OCTA在阿尔茨海默病诊断中的研究进展

阿尔茨海默病是一种进行性且不可逆转的神经系统疾病,由于视网膜和中枢神经系统有相似的胚胎起源和生理特征,眼科检查可提供简单无创的诊断方法。光学相干断层扫描技术(OCT)能够精确地测量视网膜各个组织层面的厚度,以评估视网膜的退行性改变,光学相干断层扫描血管成像(OCTA)可以提供高分辨率三维成像,从而更直观地检测视网膜血管的变化,间接地反映脑神经元和血管的病理特征。就OCT测量视网膜厚度及OCTA测量视网膜血流变化在阿尔茨海默病诊断中的研究进展进行综述。     

儿童1型糖尿病骨密度变化及影响因素分析

目的 测定儿童1型糖尿病(T1DM)患者骨密度(BMD),分析探讨骨密度变化的影响因素。方法 选取于2018年1月—2021年6月于我院收治的儿童1型糖尿病患者76例,收集性别、年龄、发病年龄、身高、体重、BMI、病程等基本资料,检测空腹血糖、空腹C肽、糖化血红蛋白(HbA1c)、血碳酸氢根(HCO3-)、血清碱性磷酸酶(ALP),应用双能X线吸收测定法测定骨密度,获取Z值。结果 76例儿童1型糖尿病患者骨密度Z值为-0.93±2.14。HbA1c、病程与骨密度Z值呈负相关,差异具有统计学意义(分别B=-0.334,P<0.001;B=-0.191,P=0.017)。结论 儿童1型糖尿病患者骨密度低于健康儿童,血糖控制不良、病程长是1型糖尿病儿童骨密度减低的危险因素。     

Pharmacokinetics and Early Tumor Response to Conventional Transarterial Chemoembolization with Sorafenib and Doxorubicin in a VX2 Rabbit Tumor Model

PurposeTo investigate the pharmacokinetics (PK) and early effects of conventional transarterial chemoembolization (TACE) using sorafenib and doxorubicin on tumor necrosis, hypoxia markers, and angiogenesis in a rabbit VX2 liver tumor model.Materials and MethodsVX2 tumor-laden New Zealand White rabbits (N = 16) were divided into 2 groups: 1 group was treated with hepatic arterial administration of ethiodized oil and doxorubicin emulsion (DOX-TACE), and the other group was treated with ethiodized oil, sorafenib, and doxorubicin emulsion (SORA-DOX-TACE). Animals were killed within 3 days of the procedure. Levels of sorafenib and doxorubicin were measured in blood, tumor, and adjacent liver using mass spectrometry. Tumor necrosis was determined by histopathological examination. Intratumoral hypoxia-inducible factor (HIF) 1α, vascular endothelial growth factor (VEGF), and microvessel density (MVD) were determined by immunohistochemistry.ResultsThe median intratumoral concentration of sorafenib in the SORA-DOX-TACE group was 17.7 μg/mL (interquartile range [IQR], 7.42–33.5 μg/mL), and its maximal plasma concentration (C_max) was 0.164 μg/mL (IQR, 0.0798–0.528 μg/mL). The intratumoral concentration and C_max of doxorubicin were similar between the groups: 4.08 μg/mL (IQR, 3.18–4.79 μg/mL) and 0.677 μg/mL (IQR, 0.315–1.23 μg/mL), respectively, in the DOX-TACE group and 1.68 μg/mL (IQR, 0.795–4.08 μg/mL) and 0.298 μg/mL (IQR, 0.241–0.64 μg/mL), respectively, in the SORA-DOX-TACE group. HIF-1α expression was increased in the SORA-DOX-TACE group than in the DOX-TACE group. Tumor volume, tumor necrosis, VEGF expression, and MVD were similar between the 2 groups.ConclusionsThe addition of sorafenib to DOX-TACE delivered to VX2 liver tumors resulted in high intratumoral and low systemic concentrations of sorafenib without altering the PK of doxorubicin.     

Effects of the Cerebral Aneurysm Treatment Method on Coil Packing Density and Its Relationship with the Ostium Area

PurposeTo test the following hypotheses: (a) balloon or stent assistance increases coil packing density (CPD) in the endovascular treatment of intracranial aneurysms, and (b) CPD correlates to ostium area (OA) and aneurysm volume (AV).Materials and MethodsThis retrospective study included 60 aneurysms (54 ruptured and 6 unruptured) treated with simple coiling (SC) (n = 18), balloon-assisted coiling (BAC) (n = 7), or stent-assisted coiling (SAC) (n = 35) at the authors’ institution between August 2017 and December 2019. AV and OA measurements were obtained from 3-dimensional digital subtraction angiography images using commercial software. Coil sizes were retrieved from patient files, and coil volume (CV) measurements were obtained from https://www.angiocalc.com/. Analysis of covariance, multivariate covariance analysis, and Pearson correlation analyses were performed.ResultsThe median value for AV, CV, CPD, and OA was 63.4 mm³ (range, 5.5–1,771.4 mm³), 23.13 mm³ (range, 2.03–296.95 mm³), 33.29% (range, 13.41%–81.02%), and 10.7 mm² (range, 2.7–49.9 mm²), respectively. Multivariate analysis showed that the CPD values were not significantly different among the treatment groups, although OA significantly differed between the SC and SAC groups (P < .05). Pearson correlations showed that similar to AV, OA was negatively correlated with CPD (r = ?0.321, P < .05).ConclusionsThe CPD value in cerebral aneurysms treated with BAC or SAC did not differ from that in aneurysms treated with SC.     

Biomechanical comparison of stemless humeral components in total shoulder arthroplasty

BackgroundThe purpose of this study was to compare initial fixation strength between various stemless and stemmed humeral components and to correlate implant fixation strength with bone mineral density (BMD).MethodsFive humeral stem designs were investigated: Stemless-A (four hollow fins), Stemless-B (central body, three solid fins), Stemless-C (central screw, peripheral rim-fit), Short stem (50 mm), and Standard stem (130 mm). Fifty cadaveric human humerii were obtained and divided into five groups. BMD within the humeral head was determined for all samples. The mean BMD was similar between groups. The 25 samples with the lowest and highest BMDs were categorized as “Low” and “High,” respectively, with a BMD threshold of 0.35 g/cm², creating BMD subgroups. After implantation, each sample underwent a standardized biomechanical testing protocol, with axial loading followed by torsional loading. Sensors attached to the specimen recorded micromotion throughout testing. Axial loading consisted of cyclic loading for 100 cycles at 3 peak forces (220, 520, and 820 N). Torsional loading consisted of 100 cycles of internal/external rotation at 0.1 Hz at 6 peak torques, or until failure (±2.5, 5, 7.5, 10, 12.5, and 15 Nm). Failure was defined as the torque at which any bone fracture, implant detachment from anchor/stem, or an excess of 50° internal/external rotation occurred. Groups and BMD subgroups were compared.ResultsAt maximal axial loading, Stemless-B demonstrated greater micromotion (540 μm) than Stemless-C (192 μm) (P = .003). Stemless-B and Stemless-A (387 μm) also had greater micromotion than Short stem (118 μm, P < .001, P = .03) and Standard stem (85 μm, P < .001, P = .01). When comparing low-BMD samples at maximal axial loading, these differences were accentuated, but comparison of high-BMD samples showed no significant differences between groups. Torsional testing demonstrated that Standard stem failed at greater torque (7.2 Nm) than Stemless-B (2.3 Nm, P < .001), Stemless-A (1.9 Nm, P < .001), and Stemless-C (3.9 Nm, P = .01). When comparing torsional testing results of low-BMD samples, both Standard stem and Short stem failed at greater torque than Stemless-B (P = .02, P = .003) and Stemless-A (P = .03, P = .004) but failed at a similar torque to Stemless-C. Torsional testing of high-BMD samples showed that Standard stem failed at a greater torque than all stemless designs.ConclusionStemless humeral implants should be used with caution in low-BMD settings (<0.35 g/cm²). A central screw and peripheral rim-fit stemless anchor design demonstrated greater fixation strength at low BMD when compared with other designs, while all stemless designs performed similarly at high BMD.Level of evidenceBasic Science Study; Cadaveric Study     

Synthetic MRI is not yet ready for morphologic and functional assessment of patellar cartilage at 1.5 Tesla

PurposeThe purpose of this study was to compare morphologic assessment and relaxometry of patellar hyaline cartilage between conventional sequences (fast spin-echo [FSE] T2-weighted fat-saturated and T2-mapping) and synthetic T2 short-TI inversion recovery (STIR) and T2 maps at 1.5 T magnetic resonance imaging (MRI).MethodThe MRI examinations of the knee obtained at 1.5 T in 49 consecutive patients were retrospectively studied. There were 21 men and 28 women with a mean age of 45 ± 17.7 (SD) years (range: 18–88 years). Conventional and synthetic acquisitions were performed, including T2-weighted fat-saturated and T2-mapping sequences. Two radiologists independently compared patellar cartilage T2-relaxation time on conventional T2-mapping and synthetic T2-mapping images. A third radiologist evaluated the patellar cartilage morphology on conventional and synthetic T2-weighted images. The presence of artifacts was also assessed. Interobserver agreement for quantitative variables was assessed using intraclass correlation coefficient (ICC).ResultsIn vitro, conventional and synthetic T2 maps yielded similar mean T2 values 58.5 ± 2.3 (SD) ms and 58.8 ± 2.6 (SD) ms, respectively (P = 0.414) and 6% lower than the expected experimental values (P = 0.038). Synthetic images allowed for a 15% reduction in examination time compared to conventional images. On conventional sequences, patellar chondropathy was identified in 35 patients (35/49; 71%) with a mean chondropathy grade of 4.8 ± 4.8 (SD). On synthetic images, 28 patients (28/49; 57%) were diagnosed with patellar chondropathy, with a significant 14% difference (P = 0.009) and lower chondropathy scores (3.7 ± 4.9 [SD]) compared to conventional images. Motion artifacts were more frequently observed on synthetic images (18%) than on conventional ones (6%). The interobserver agreement was excellent for both conventional and synthetic T2 maps (ICC > 0.83). Mean cartilage T2 values were significantly greater on synthetic images (36.2 ± 3.8 [SD] ms; range: 29-46 ms) relative to conventional T2 maps (31.8 ± 4.1 [SD] ms; range: 26-49 ms) (P < 0.0001).ConclusionDespite a decrease in examination duration, synthetic images convey lower diagnostic performance for chondropathy, greater prevalence of motion artifacts, and an overestimation of T2 values compared to conventional MRI sequences.