Altered Retinal Perfusion in Patients with Inactive Graves Ophthalmopathy Using Optical Coherence Tomography Angiography

Objective: The aim of this study was to evaluate retinal and optic nerve head (ONH) perfusion in patients with inactive Graves ophthalmopathy (GO) and compare it to healthy controls using optical coherence tomography angiography (OCTA).Methods: Twenty-nine eyes of 29 patients with inactive GO (study group) and 29 eyes of 29 healthy subjects (control group) were included in this study. The vessel density (VD) data in the superficial and deep retinal OCT angiogram of the macula and the radial peripapillary capillary network (RPC) were extracted and analyzed. OCTA was performed using RTVue XR Avanti with AngioVue (Optovue Inc, Fremont, CA). Clinical activity was evaluated using the clinical activity score, the severity assessment using the NOSPECS classification.Results: The VD in the superficial OCT angiogram and in the OCT angiogram of the ONH was significantly lower in the GO group when compared to the control group (whole en face, P = .016; parafovea, P = .026; RPC peripapillary, P = .027). There was no significant correlation between VD and functional parameters or the NOSPECS classification.Conclusion: Macular VD and ONH capillary density measured using OCTA were significantly lower in the study group compared to healthy controls. Noninvasive quantitative analysis of retinal perfusion using OCTA could be useful in monitoring patients with GO.Abbreviations: CAS = clinical activity score; GO = Graves ophthalmopathy; OCTA = optical coherence tomography angiography; ONH = optic nerve head; RPC = radial peripapillary capillary; rSp = Spearman's correlation coefficient; VD = vessel density     

OCTA用于检测不同屈光人群的黄斑区视网膜密度和厚度及其相关性分析

目的:采用光学相干断层扫描血管成像技术(OCTA)检测不同屈光人群的黄斑区视网膜密度及厚度并分析其相关性。方法:选取2016年2月～2018年2月我院收治的近视患者200例为研究对象,根据等效球镜度数的差异将其分为轻度近视组(-0.50～-2.75D)52例、中度近视组(-3.00～-5.75D)46例、高度近视组(-6.00～-8.75D)48例、超高度近视组(≤-0.90D)54例。所有患者均进行OCTA检测,比较各组患者黄斑区不同区域视网膜血管密度以及厚度的差异。结果:轻度近视组、中度近视组、高度近视组、超高度近视组等效球镜均呈逐渐降低趋势,而眼轴长度均呈逐渐升高趋势,各组间对比差异有统计学意义(P0.05)。超高度近视组患者中心凹、中心凹旁、颞侧、上方、鼻侧、下方视网膜血管密度和中心凹、中心凹旁、颞侧、上方、鼻侧、下方视网膜厚度相比轻度近视组、中度近视组、高度近视组均显著降低(P0.05)。经Pearson相关性结果显示:近视屈光人群的黄斑中心凹以及上方视网膜血管密度以及视网膜厚度呈正相关关系(P0.05)。结论:采用OCTA检测不同屈光人群的黄斑区视网膜密度及厚度,结果表明近视屈光度患者的黄斑区视网膜密度增加以及黄斑区视网膜厚度的增厚呈正相关关系。     

Role of Magnetic Resonance Imaging in the Assessment of Active Thyroid-Associated Ophthalmopathy Patients with Long Disease Duration

Objective: In thyroid-associated ophthalmopathy (TAO), long disease duration is negatively correlated with the response to immunosuppression treatment. The current treatment decision-making process does not involve magnetic resonance imaging (MRI); thus, we investigated the predictive value of MRI parameters for the immunosuppressive response in active moderate to severe TAO patients with different disease durations.Methods: We retrospectively analyzed the baseline MRI parameters of active TAO patients treated with guideline-recommended weekly glucocorticoid therapy in our center. Data were stratified by the quartile of disease duration. The signal intensity ratio (SIR) of T2-weighted images was used to describe the activity of extraocular muscles (EOMs).Results: Compared to the lowest quartile of disease duration, SIR values of EOMs were significantly lower in quartile 3 (Q3) and quartile 4 (Q4). Meanwhile, the clinical activity score (CAS) curve did not change in parallel and was not correlated with the SIR curve. In the highest quartile of disease duration, nonresponders had significantly lower SIR values of the most inflamed muscle (P =.03) and the medial rectus (P =.004) than did the responders, while no such significance was observed in patients within the lower 3 quartiles. A multivariable predictive model (including CAS, TAO duration, and SIR value) was established in each quartile. The fit of the model was better than CAS with regard to prognostic prediction and showed a high positive predictive value (Model 1: 86.67%; Model 2: 92.86%) and negative predictive value (Model 1: 88.89%; Model 2: 90%) in the top quartile.Conclusion: The anterior manifestation assessed by CAS is not always consistent with retro-orbital activity in long-term TAO patients. CAS is sufficient to reflect disease activity in short-term TAO patients. The supplementation of CAS with orbital MRI would be valuable in selecting appropriate active patients with a long disease duration.Abbreviations: AUC = area under the curve; CAS = clinical activity score; EOM = extraocular muscle; FT3 = free triiodothyronine; FT4 = free thyroxine; GC = glucocorticoid; ivGC = intravenous glucocorticoids; MRI = magnetic resonance imaging; NPV = negative predictive value; PPV = positive predictive value; SIR = signal intensity ratio; TAO = thyroid-associated ophthalmopathy; TRAb = thyroid-stimulating hormone receptor antibody; TSH = thyroid-stimulating hormone     

Normative intercapillary distance and vessel density data in the temporal retina assessed by wide-field spectral-domain optical coherence tomography angiography

A limitation of conventional optical coherence tomography angiography (OCTA) is the limited field of view normally used in data acquisition. As the technology improves, larger fields of view that capture information away from the macular are being explored in order to provide an enhanced ability to detect pathology. However, normative measurements for important OCTA metrics like vessel density and intercapillary distance are not currently well-characterized in the peripheral retina. In this prospective study, we measured vessel density and intercapillary distance of the superficial vascular complex, ganglion cell layer plexus, and deep capillary plexus in montaged macular/temporal scans from 53 (33 men) healthy volunteers. Vessel density and intercapillary distance were also compared across different regions of the retina, including along arcs at separate distance from the fovea. Compared to the central macular region, the temporal retina had significantly lower vessel density, decreased thickness, and greater intercapillary distance in the superficial vascular complex, GCLP ganglion cell layer plexus, and deep capillary plexus (Wilcoxon rank sum test P < 0.001), with each of the plexuses examined here showing a general decrease in vessel density and an increase in intercapillary distance towards the temporal region. No significant difference was noted comparing corresponding vessel density and intercapillary distance regions above and below the macula, and multiple linear regression showed that age and intraocular pressure were not associated with vessel density and intercapillary distance in most models. Repeatability analysis reported as intraclass correlation coefficients demonstrated moderate to excellent reliability of vessel density and intercapillary distance in all OCTA layers. These results should help provide an enhanced baseline to help identify vascular pathology in the peripheral retina.     

Quantification of diabetic macular ischemia using novel three‐dimensional optical coherence tomography angiography metrics

We applied three‐dimensional (3D) analysis to optical coherence tomography angiography (OCTA) to measure macular ischemia in eyes affected by non‐proliferative diabetic retinopathy (DR). A previously validated algorithm was applied to OCTA data in order to obtain 3D visualization of the retinal vasculature. Successively, a global thresholding algorithm was applied and two novel quantitative metrics were introduced: 3D vascular volume and 3D perfusion density. Two‐dimensional (2D) OCTA metrics were also obtained with different binarization thresholds for comparison. Of the 30 patients included, 15 were diagnosed with DR and 15 were controls. The 3D vascular volume and 3D perfusion density were reduced in DR eyes (P < .0001). The 2D variables also significantly differ between groups. The 3D perfusion density had the highest area under the receiver operating characteristic curve (0.964) among tested variables. Assessing quantitative perfusion using 3D analysis is reliable and promising, and with an elevated diagnostic efficacy in identifying DR eyes.     

An automated framework to quantify areas of regional ischemia in retinal vascular diseases with OCT angiography

In this observational and cross‐sectional study, capillary nonperfusion (CNP) and vascular changes in branch retinal vein occlusion (BRVO, sample size [n] = 26) and choroidal neovascularization (CNV, n = 29) were evaluated. Subjects underwent imaging using Optical coherence tomography angiography (Angiovue OCTA, RTVue XR, Optovue Inc., Fremont, California). Local fractal analysis was applied to the OCTA images of superficial, deep and choriocapillaris layer. CNP area (BRVO eyes) and vascular parameters were computed using local fractal‐based method. Sensitivity and specificity of vascular parameters were assessed with receiver operating characteristics curve. Automated CNP area showed excellent agreement with manually quantified CNP areas in both superficial (intraclass coefficient [ICC] = 0.96) and deep (ICC = 0.96) layers. BRVO eyes showed significantly altered (P < .05) vascular parameters in both superficial and deep layer as compared to normal eyes (n = 30). CNVM eyes had significantly higher capillary free zones (P < .001) as compared to normal eyes. In normal vs BRVO eyes, vessel density and spacing between the large vessels had similar area under the curve (AUC) (P > .05) in both superficial (0.97 and 0.97, respectively) and deep layer (0.99 and 0.98, respectively). Further, capillary free zones showed high AUC (0.92) in differentiating CNV eyes from normal eyes.      

Novel rodent models for macular research

Background

Many disabling human retinal disorders involve the central retina, particularly the macula. However, the commonly used rodent models in research, mouse and rat, do not possess a macula. The purpose of this study was to identify small laboratory rodents with a significant central region as potential new models for macular research.

Methodology/Principal Findings

Gerbillus perpallidus, Meriones unguiculatus and Phodopus campbelli, laboratory rodents less commonly used in retinal research, were subjected to confocal scanning laser ophthalmoscopy (cSLO), fluorescein and indocyanine green angiography, and spectral-domain optical coherence tomography (SD-OCT) using standard equipment (Heidelberg Engineering HRA1 and Spectralis™) adapted to small rodent eyes. The existence of a visual streak-like pattern was assessed on the basis of vascular topography, retinal thickness, and the topography of retinal ganglion cells and cone photoreceptors. All three species examined showed evidence of a significant horizontal streak-like specialization. cSLO angiography and retinal wholemounts revealed that superficial retinal blood vessels typically ramify and narrow into a sparse capillary net at the border of the respective area located dorsal to the optic nerve. Similar to the macular region, there was an absence of larger blood vessels in the streak region. Furthermore, the thickness of the photoreceptor layer and the population density of neurons in the ganglion cell layer were markedly increased in the visual streak region.

Conclusions/Significance

The retinal specializations of Gerbillus perpallidus, Meriones unguiculatus and Phodopus campbelli resemble features of the primate macula. Hence, the rodents reported here may serve to study aspects of macular development and diseases like age-related macular degeneration and diabetic macular edema, and the preclinical assessment of therapeutic strategies.     

Effects of Bisphosphonates on Osteoporosis Induced by Duchenne Muscular Dystrophy: A Prospective Study

Objective: Duchenne muscular dystrophy (DMD) is a severe X-linked progressive neuromuscular disease that brings a significantly increased risk of osteoporosis and bone fractures. We prospectively evaluated the effects of oral and intravenous bisphosphonates on the bones of children with DMD.Methods: This study included a total of 52 children with DMD. They were divided into zoledronic acid (ZOL), alendronate (ALN), and control groups according to bone mineral density (BMD) and history of fragility fractures. For 2 years, all patients took calcium, vitamin D, and calcitriol. Meanwhile, 17 patients received infusions of ZOL, and 18 patients received ALN. BMD, serum levels of alkaline phosphatase (ALP) and the cross-linked C-telopeptide of type I collagen (β-CTX) were evaluated.Results: After 24 months of treatment, the percentage changes in lumbar spine BMD were 23.2 ± 9.7% and 23.6 ± 8.8% in the ZOL and ALN groups (all P<.01 vs. baseline). The increases did not differ between the ZOL and ALN groups, but were significantly larger than those of the control group (P<.01). Serum β-CTX and ALP levels, respectively, were decreased by 44.4 ± 18.0% and 31.9 ± 26.7% in the ZOL group and by 36.0 ± 20.3% and 25.8 ± 14.4% in the ALN group (all P<.01 vs. baseline).Conclusion: Zoledronic acid and alendronate had similar protective effects to increase bone mineral density and reduce bone resorption in children with DMD, which were superior to treatment of calcium, vitamin D, and calcitriol.Abbreviations: 25OHD = 25 hydroxyvitamin D; ALN = alendro-nate; ALP = alkaline phosphatase; ALT = alanine aminotransferase; BMD = bone mineral density; BP = bisphosphonate; Ca = calcium; β-CTX = cross-linked C-telopeptide of type I collagen; DMD = Duchenne muscular dystrophy; FN = femoral neck; GC = glucocorticoid; LS = lumbar spine; ZOL = zoledronic acid     

Primary Hyperparathyroidism: Comparing Between Solid and Cystic Adenomas and the Efficacy of Ultrasound and Single-Photon Emission Computed Tomography in their Diagnosis

Objective: Primary hyperparathyroidism (PHPT) is a disorder that results from abnormal functioning of the parathyroid glands. The purpose of this study was to compare cystic and solid adenomas by analyzing different variables associated with PHPT and parathyroid adenomas (age, calcium, phosphorus, and parathyroid hormone &lsqb;PTH] levels, adenoma volume) while comparing the efficacy of ultrasound and single-photon emission computed tomography in differentiating between both types of adenoma.Methods: From 152 patients diagnosed with PHPT between January 2013 and 2014, only 109 patients who had positive ultrasonographic findings for single parathyroid adenoma were included in the study.Results: A total of 26 patients had cystic adenomas and 83 patients had solid adenomas. Sestamibi (MIBI) was negative in 50% of the cystic adenoma group and 27.7% of the solid adenoma group, with an overall technetium-MIBI efficacy of 67%. Age, phosphorus level, and adenoma volume were significantly higher in patients with cystic adenomas (P = .001, P = .02, and P = .02, respectively), whereas calcium and PTH levels were significantly higher in patients with solid adenomas (P = .02, P = .038, respectively). MIBI had a significant correlation with PTH levels (P = .031) and adenoma volume (P = .05) only in patients with solid adenomas. No significant correlation was found between sex and type of parathyroid adenoma.Conclusion: The current study is the first to compare age, PTH levels, and adenoma volume between cystic and solid adenoma patients, providing more information for the poorly understood pathology of cystic adenomas. Our findings showed that age and calcium and PTH levels are significantly higher in patients with solid adenomas, whereas adenoma volume and phosphorus levels are significantly higher in patients with cystic adenomas.Abbreviations: BMD = bone mineral density GFR = glomerular filtration rate iPTH = intact parathyroid hormone MIBI = sestamibi PHPT = primary hyperparathyroidism PTH = parathyroid hormone SPECT = single-photon emission computed tomography Tc = technetium US = ultrasound     

Vascular changes precede tomographic changes in diabetic eyes without retinopathy and improve artificial intelligence diagnostics

The purpose of this study was to evaluate early vascular and tomographic changes in the retina of diabetic patients using artificial intelligence (AI). The study included 74 age‐matched normal eyes, 171 diabetic eyes without retinopathy (DWR) eyes and 69 mild non‐proliferative diabetic retinopathy (NPDR) eyes. All patients underwent optical coherence tomography angiography (OCTA) imaging. Tomographic features (thickness and volume) were derived from the OCTA B‐scans. These features were used in AI models. Both OCT and OCTA features showed significant differences between the groups (P < .05). However, the OCTA features indicated early retinal changes in DWR eyes better than OCT (P < .05). In the AI model using both OCT and OCTA features simultaneously, the best area under the curve of 0.91 ± 0.02 was obtained (P < .05). Thus, the combined use of AI, OCT and OCTA significantly improved the early diagnosis of diabetic changes in the retina.     

Increased Bone Turnover in Type 2 Diabetes Patients Randomized to Bariatric Surgery Versus Medical Therapy at 5 Years

Objective: The aim of our study was to determine the 5-year outcomes of bariatric surgery versus intensive medical therapy on bone turnover in patients with type 2 diabetes mellitus (T2DM) from the STAMPEDE trial.Methods: This was an ancillary investigation of a 5-year randomized control trial at a single tertiary care center involving 95 patients aged 48.5 ± 8 years with obesity (body mass index &lsqb;BMI], 36.5 ± 3.6 kg/m²) and uncontrolled T2DM (glycated hemoglobin 9.3 ± 1.6% &lsqb;78 mmol/mol]). Patients were randomized to intensive medical therapy (IMT; n = 25), Roux-en-Y gastric bypass (RYGB; n = 37), or sleeve gastrectomy (SG; n = 33) for diabetes treatment. Bone formation marker osteocalcin (OC), bone resorption marker serum C-telopeptide of type 1 collagen (CTX), and intact parathyroid hormone (PTH) were assessed at baseline and 5 years postintervention. Analysis with key clinical parameters and outcomes (i.e., age, menopausal status, gender, weight loss) was performed.Results: Percent change in CTX at 5 years increased in both surgical groups, by 137 ± 108% in RYGB (P<.001) and 61.1 ± 90% in SG (P<.001) compared to 29.8 ± 93% in IMT (P = .12). OC also increased from baseline in the surgical cohorts, by 138 ± 19% in RYGB (P<.001) and 71 ± 69% in SG (P<.001) compared to 43.8 ± 121.1% in IMT (P = .83). Increases in both CTX and OC correlated linearly with increases in PTH levels in RYGB patients (P<.001). Increase in CTX correlated with decreased BMI in SG patients (P = .039).Conclusion: In patients with T2DM, bone turnover remains chronically elevated at 5 years following RYGB, and to a lesser extent in SG patients.Abbreviations: BMI = body mass index; BTM = bone turnover marker; CTX = C-telopeptide of type 1 collagen; HbA1c = glycated hemoglobin; IMT = intensive medical therapy; OC = osteocalcin; PPI = proton-pump inhibitor; PTH = parathyroid hormone; RYGB = Roux-en-Y gastric bypass; SG = sleeve gastrectomy; T2DM = type 2 diabetes mellitus; TZD = thiazolidinedione     

Trabecular Bone Score Change Differs with Regard to 25(OH)D Levels in Patients Treated for Adult-Onset Growth Hormone Deficiency

Objective: Vitamin D is important in bone health. However, potential relationships of concomitant vitamin D deficiency with growth hormone deficiency (GHD) and the possibility that vitamin D inadequacy may alter the skeletal effects of growth hormone (GH) replacement therapy have not been adequately evaluated.Methods: A prospective study was conducted in adult-onset GHD patients treated with recombinant human GH (rhGH) for 2 years. Trabecular bone score (TBS), lumbar spine (LS) bone mineral density (BMD), total hip (TH) BMD, and 25-hydroxyvitamin D (25(OH)D) levels were assessed at baseline and 24 months. The study cohort was divided based on 25(OH)D levels into 2 groups with the cutoff defined as the 50^th percentile at each follow-up time point.Results: Fifty-seven patients (29 males/28 females, mean age 34.4 years) were studied. After 24 months of GH replacement, LS BMD increased by 7.6% and TH BMD increased by 4.5% (both P<.05), with no difference according to 25(OH)D levels. TBS increased (+1.39 ± 3.6%) in those whose 25(OH)D was above the 50^th percentile but decreased (-1.36 ± 5.6%, P<.05) in the cohort below the 50^th percentile of 25(OH)D. Positive correlations were observed between baseline levels of IGF-1 and 25(OH)D (R = 0.37, P<.001) and between 24-month 25(OH)D and TBS (R = 0.25, P<.05).Conclusion: A differential effect of GH on TBS change was observed; TBS increased only in the cohort with 25(OH)D above the 50^th percentile. Vitamin D sufficiency may be required to obtain optimal effects of GH treatment on bone quality, as assessed by TBS, in GHD adults.Abbreviations:AO-GHD = adult-onset GHDBMD = bone mineral densityBMI = body mass indexCa = calciumCTx = carboxyterminal collagen crosslinksCV = coefficient of variationDXA = dual energy X-ray absorptiometryECLIA = enzyme-labeled chemiluminescent immunometric assayGH = growth hormoneGHD = growth hormone deficiencyIGF-1 = insulin-like growth factor 1LS BMD = lumbar spine BMDOC = osteocalcin25(OH)D = 25-hydroxyvitamin DP = phosphorusPTH = parathyroid hormonerhGH = recombinant human GHTBS = trabecular bone scoreTH BMD = total hip BMD     

亚热带6种树种细根序级结构和形态特征

以福建省建瓯市万木林自然保护区内占优势的6种天然林树种(沉水樟Cinnamomum micranthum,CIM;观光木Tsoongiodendron odorum Chun,TOC;浙江桂Cinnamomum chekiangense,CIC;罗浮栲Castanopsis fabri,CAF;细柄阿丁枫Altingiagracilipes,ALG;米槠Castanopsis carlesii,CAC)为研究对象,对其1—5级细根的结构,形态特征及生物量进行了分析。结果表明:沉水樟,细柄阿丁枫和米槠细根分支比表现出在1,2级(4倍以上)明显大于其它序级(3倍左右);其余3种树种则是在3,4级的细根分支比最大,其中浙江桂达到8.65倍,其它序级则大致为3倍左右。6种树种1,2级细根数量占到总数的70%—90%。6种树种细根直径,根长,组织密度随序级升高逐渐增大,比根长减小,生物量未表现出一致的变化规律,6种树种生物量主要集中在高级根部分。方差分析表明,树种对细根分支比例有显著影响(P<0.05),浙江桂和米槠细根分支水平对分支比例有极显著影响(P<0.01),其余4种树种分支水平对分支比例有显著影响(P<0.05),树种和分支水平的交互作用对6种树种细根分支比均有极显著的影响(P<0.01);树种对细根根长,直径以及生物量均有极显著影响(P<0.01),对比根长有显著影响(P<0.05),而对组织密度的影响则不显著(P>0.05);树种和序级的交互作用对细根根长,直径以及生物量均有极显著影响(P<0.01),对组织密度有显著影响(P<0.05),对比根长影响不显著(P>0.05)。序级对6种树种细根根长,直径,比根长以及生物量的影响并未达到一致,对6种树种细根组织密度有极显著影响(P<0.01)。树种间1—4级根的比根长变异主要由组织密度引起,而5级根的比根长变异则由直径引起,同时在1级根中组织密度与直径呈现出权衡的关系。6种树种细根数量,直径,根长,比根长,组织密度以及生物量与序级之间回归分析发现它们与序级之间具有指数函数,线性函数,二次函数,三次函数或者幂函数关系。     

The Association Between Tumor Tissue Calcification,Obesity, and Thyroid Cancer Invasiveness In A Cohort Study

Objective: We examined the relationships between tumor tissue calcifications of papillary thyroid cancer (PTC), body mass index (BMI), and tumor invasiveness.Methods: This was a retrospective analysis of 13,995 patients with PTC. Comparisons were made between the clinical and pathologic features of the tumor tissue calcifications group and non–tumor tissue calcifications group. Odds ratios (ORs) of tumor tissue calcifications, BMI, and tumor invasiveness features were calculated using a binary logistic regression model. We analyzed the relationship between tumor tissue calcifications and certain characteristics of thyroid cancer based on the pathologic findings.Results: BMI was positively correlated with tumor tissue calcifications in patients with PTC (OR, 1.015; P = .011), and obesity increased the risk of tumor tissue calcifications (OR, 1.374; P = .038). Calcifications were positively correlated with T-size (OR, 1.899; P<.001), multifocality (OR, 1.217; P<.001), extrathyroidal extension (ETE) (OR, 1.287; P<.001), high T-stage (OR, 1.765; P<.001), N+ (OR, 1.763; P<.001), and a higher number of lymph node metastases (OR, 1.985; P<.001). Compared with normal-weight patients with tumor tissue calcifications, obese patients with tumor tissue calcifications had an increased risk of ETE (OR_obesity, 1.765 vs. OR_normal, 1.300) and N+ (OR_obesity, 1.992 vs. OR_normal, 1.784).Conclusion: Tumor tissue calcifications are positively correlated with the invasiveness of PTC. Obesity further promotes the risk of tumor invasiveness in PTC combined with tumor tissue calcifications. These findings suggest that more comprehensive evaluations by trained pathologists may help physicians identify the optimal therapeutic regimens in the postoperative period.Abbreviations: BMI = body mass index; CI = confidence interval; ETE = extrathyroidal extension; FT3 = free triiodothyronine; OR = odds ratio; PTC = papillary thyroid carcinoma; RET = rearranged during transfection; TTC = tumor tissue calcification; US = ultrasonography; USC = ultrasonography calcification; WHO = World Health Organization     

Meat eating and nutritional quality of lambs sired by high and low muscle density rams

Intramuscular fat (IMF) content affects eating and nutritional quality of lamb meat. Muscle density measured by computer tomography is an in vivo proxy measure of IMF content that affects eating and nutritional quality of lamb meat. Lambs sired by high muscle density (HMD) or low muscle density (LMD) rams, selected for slaughter on commercial criteria were measured for meat quality and nutritional traits. A restricted maximum likelihood model was used to compare lamb traits. Additionally, regression analysis of sire estimated breeding value (EBV) for muscle density was performed for each meat quality trait. Muscle density EBV had a negative regression with IMF content (P < 0.001). For each unit increase in muscle density EBV, there was a significant decrease in loin (− 1.69 mg/100 g fresh weight) and topside IMF (− 0.03 mg/100 g fresh weight). Muscle density EBV had a negative regression with grouped saturated and monounsaturated fatty acids concentration (and monounsaturated proportion P < 0.001). Muscle density EBV had a negative regression with loin sensory traits tenderness, juiciness and overall liking and many novel tenderness sensory traits measured (P < 0.05). Selecting for LMD EBV increased IMF content and favourable meat eating quality traits. In contrast, sire muscle density EBV had a positive regression with loin polyunsaturated:saturated fat ratio and grouped polyunsaturated proportion traits (including total polyunsaturated proportion, total omega-6 (n-6) and total omega-3 (n-3) fatty acids (P < 0.001). This is explained by the fact that as sire muscle density EBV increases, polyunsaturated fatty acid proportion increases and the proportion of saturated and monounsaturated fatty acid content decreases. Muscle density EBV had a positive regression with shear force and the novel toughness sensory traits (P < 0.05). Selection for HMD EBV's increased shear force and toughness traits, which is unfavourable for the consumer. Low muscle density sired meat had higher meat colour traits chroma/saturation (+ 0.64, SD 2.30, P = 0.012), redness (+ 0.52, SD 1.91, P = 0.012) and yellowness (+ 0.31, SD 1.49, P = 0.08) compared to HMD sired meat. Selection for LMD could be used within a breeding programme to increase IMF content and enhance both meat colour and improve eating quality parameters.     

Decrease in Acromegaly-Associated Thyroid Enlargement after Normalization of IGF-1 Levels: A Prospective Observation and in Vitro Study

Objective: Goiter occurs at high frequency in acromegaly patients. Whether normalization of insulin-like growth factor 1 (IGF-1) levels could decrease goiter and thyroid volume remains unclear.Methods: Thyroid hormone levels and ultrasound measurements were assessed in 101 acromegaly patients, compared with 108 patients with nonfunctioning pituitary adenoma (NFPA) and 55 healthy controls. Thirty-four acromegaly patients underwent repeat evaluation 1 year post–transsphenoidal surgery. The effect of IGF-1 on thyroid cell proliferation, cell cycle, and apoptosis was evaluated in vitro.Results: Acromegaly patients showed larger thyroid volume than those with NFPAs (18.32 mL vs. 9.91 mL; P<.001) and healthy controls (18.32 mL vs. 9.63 mL; P<.001). Duration of acromegaly was shown to be independently associated with thyroid volume enlargement (B = 0.259; 95% confidence interval, 0.162 to 0.357) in multivariate analysis. At follow-up, the median thyroid volume decreased from 22.74 to 17.87 mL in the cured group (n = 20; P = .003), but the number of nodular goiters showed no significant change. Serum free thyroxine levels decreased from 13.76 to 10.08 pmol/L in the cured group (P = .006) but increased from 9.28 to 12.09 pmol/L in the active group (P = .013). Change in thyroid volume was significantly correlated with IGF-1 level (r = 0.37; P = .029). In vitro, IGF-1 time- and dose-dependently promoted proliferation and secretory function of thyroid cells by enhancing cell cycle shift from the G1/S to G2/M phase and suppressing apoptosis.Conclusion: Acromegaly-associated thyroid volume increase, but not nodular goiter, could be reversed in cured acromegaly. IGF-1 time- and dose-dependently promoted the proliferation and secretory function of thyroid cells.Abbreviations: CCK-8 = Cell Counting Kit-8; fT3 = free triiodothyronine; fT4 = free thyroxine; GH = growth hormone; IGF-1 = insulin-like growth factor 1; MRI = magnetic resonance imaging; NFPA = nonfunctioning pituitary adenoma; qRT-PCR = quantitative real-time–polymerase chain reaction; TSH = thyroid-stimulating hormone     

Thyroid-Associated Ophthalmopathy: Preliminary Study Using T2 Mapping to Characterize Intraorbital Optic Nerve Changes Before Dysthyroid Optic Neuropathy

ObjectiveTo evaluate the performance of T2 mapping in detecting intraorbital optic nerve (ON) changes in patients with thyroid-associated ophthalmopathy (TAO) before the onset of dysthyroid optic neuropathy (DON).MethodsThirty-five patients with TAO and without DON (21 active, 14 inactive) and 21 healthy controls (HCs) were enrolled. Magnetic resonance imaging-derived parameters of T2 relaxation time (T2RT) at the intraorbital ON, extraocular muscle (EOM), orbital fat, exophthalmos, summed thickness of EOMs, orbital fat thickness, and clinical variables were compared. Correlations between T2RT at the ON and other variables were assessed.ResultsPatients with TAO showed significantly higher T2RTs at the intraorbital ON than HCs (P < .001). Patients with active TAO had significantly higher T2RTs than those with inactive TAO and HCs (P < .001). Differences between patients with inactive TAO and HCs were insignificant (P > .05/3). T2RT at the intraorbital ON was positively correlated with clinical activity score, modified NOSPECS score, T2RT at EOM, exophthalmos, and summed thickness of EOMs in the TAO group (P ≤ .003) and negatively correlated with visual acuity (P = .033) and visual field indices (P = .030) in patients with active TAO. A T2RT cutoff of 82.9 ms for the intraorbital ON distinguished active TAO and healthy eyes optimally (area under the curve, 0.800; sensitivity, 85.7%; specificity, 64.3%).ConclusionT2RT detects disturbance in the intraorbital ON in patients with TAO, especially active TAO, before DON develops. T2 mapping has a potential for noninvasive evaluation of ON changes in patients with TAO.     

改良眼底激光光凝合康柏西普治疗增殖性糖尿病视网膜病变的效果及对视力水平、黄斑区血流密度的影响

摘要 目的：探究改良眼底激光光凝联合康柏西普治疗增殖性糖尿病视网膜病变（PDR）的效果及对视力水平、黄斑区血流密度的影响。方法：回顾性分析2019.06-2022.06于我院接受改良眼底激光光凝治疗的62例（124眼）PDR患者临床资料,纳入对照组,回顾性分析同期于我院接受改良眼底激光光凝联合康柏西普治疗的62例（124眼）PDR患者临床资料,纳入试验组。比较治疗前和治疗后3个月两组患者视力水平[最佳矫正视力（BCVA）、视野指数（VFI）、视野平均缺损（MD）]、视网膜中央动脉血流动力学[峰值血流速度（PSV）、平均血流速度（MV）、搏动指数（PI）、阻力指数（RI）]、黄斑区血流密度[浅层毛细血管丛（SCP）、深层毛细血管丛（DCP）]、生活质量[低视力者生存质量量表（CLVQOL）]差异,记录3个月内两组患者并发症（黄斑水肿、高眼压、视网膜出血）发生情况。结果：治疗后3个月,两组患者BCVA、PSV、MV、SCP、DCP、CLVQOL较治疗前升高,试验组高于对照组（P均<0.05）;而VFI、MD、PI、RI水平降低,试验组低于对照组（P均<0.05）;两组患者术后并发症无显著性差异（P>0.05）。结论：改良眼底激光光凝治疗联合康柏西普治疗可增强PDR患者视力功能,改善患者视网膜中央动脉血流动力学及黄斑区血流密度,提高生活质量。     

Associations Between Triglyceride/High-Density Lipoprotein Cholesterol Ratio and Micro- and Macroangiopathies in Type 2 Diabetes Mellitus

Objective: The triglyceride (TG) to high-density lipoprotein cholesterol (HDL-C) ratio has been reported to be a marker of insulin resistance. The aim of this study was to investigate associations between the TG/HDL-C ratio and micro- and macroangiopathies in patients with type 2 diabetes mellitus (DM).Methods: A total of 1,981 (851 male and 1,130 female) patients with type 2 DM were enrolled from our outpatient clinic. These patients were stratified into 4 groups according to TG/HDL-C ratio quartiles.Results: There were significant trends for stepwise increases in albuminuria ≥30 mg/g (P<.001), coronary artery disease (CAD, P =.040), cerebrovascular disease (CVA, P =.002) and ankle-brachial index (ABI) <0.9 (P =.001) corresponding to TG/HDL-C ratio quartiles, but not diabetic retinopathy (P =.105). Furthermore, quartile 4 of the TG/HDL-C ratio was significantly associated with albuminuria, CAD, CVA, and ABI <0.9 after multivariate analysis compared to quartile 1.Conclusion: A high TG/HDL-C ratio was significantly associated with albuminuria, CAD, CVA, and peripheral artery occlusive disease (PAOD) in patients with DM, which translated into an increased risk of cardiovascular disease.Abbreviations: ABI = ankle-brachial index; ACEI = angiotensin-converting enzyme inhibitor; ARB = angiotensin II receptor blocker; BMI = body mass index; CAD = coronary artery disease; CI = confidence interval; CVA = cerebrovascular disease; DM = diabetes mellitus, DR = diabetic retinopathy; eGFR = estimated glomerular filtration rate; HbA1c = glycated hemoglobin A1c; HDL-C = high-density lipoprotein cholesterol; OR = odds ratio; PAOD = peripheral artery occlusive disease; TGs = triglycerides     

Addressing Pitfalls in Management of Diabetic Ketoacidosis with a Standardized Protocol

Objective: To determine the efficacy and safety of a diabetic ketoacidosis (DKA)-Power Plan (PP) for guiding intravenous (IV) insulin infusions prior to anion gap (AG) closure and administering subcutaneous (SC) insulin ≥1 hour before discontinuing IV insulin.Methods: Retrospective chart review of patients with DKA before (pre-PP) (n = 60) and following (post-PP) (n = 60) implementation of a DKA-PP. Groups were compared for percentage of patients for whom IV insulin therapy was continued until AG closure, the percentage of patients receiving SC insulin ≥1 hour before discontinuation of IV insulin, and percentage of patients with rebound DKA during the index hospitalization.Results: Admission plasma glucose (514 mg/dL vs. 500 mg/dL; P = .36) and venous pH (7.2 vs. 7.2; P = .57) were similar in pre- and post-PP groups. Inappropriate discontinuation of IV insulin occurred less frequently in post-PP patients (28% vs. 7%; P = .007), with a lower frequency of rebound DKA (40% vs. 8%; P = .001) following acute management. More post-PP patients received SC insulin ≥1 hour before discontinuation of IV insulin (65% vs. 78%; P = .05).Conclusion: Implementation of a DKA-PP was associated with appropriate discontinuation of IV insulin in more patients, more frequent administration of SC insulin ≥1 hour prior to discontinuation of IV insulin, and fewer episodes of rebound DKA.Abbreviations: ADA = American Diabetes Association; AG = anion gap; BG = blood glucose; DKA = diabetic ketoacidosis; DKA-PP = DKA-Power Plan; ICU = intensive care unit; IQR = interquartile range; IV = intravenous; IVF = IV fluid; LOS = length of stay; SC = subcutaneous