Lassiterogden3697

Finally, we showed that daily antiprotease treatment counteracted the phenotypes of C/EBPα-knockout mice. In human studies, CEBPA expression in the lung was downregulated in patients with emphysema, and 6 smokers with centrilobular emphysema (CLE) showed a significant reduction in LEKTI in the small airways compared to 22 non-CLE smokers. LEKTI downregulation in the small airways was associated with disease development during murine small airway injury and CLE in humans, suggesting that LEKTI might be a key factor linking small airway injury to the development of emphysema.OBJECTIVE The purpose of this study is to assess the outcomes of symptomatic and asymptomatic solitary dilated ducts detected on mammography, ultrasound, and MRI. METHODS All cases of isolated solitary dilated ducts between January 1, 2009 and December 31, 2016 in non-lactating females were reviewed. Clinical data, including patient's age, breast cancer history, and pathology results were collected. Imaging was reviewed, and indication for the exam, breast density, maximum diameter of the dilated duct on ultrasound, presence of an intraductal mass, presence of intraductal vascularity, presence of intraductal echogenicity, and subareolar or peripheral location of the dilated duct were recorded. RESULTS 87 cases of solitary dilated ducts were assessed in this study, of which 3 were malignant, resulting in a positive predictive value of 3.5% (3/87). No malignancy was identified in asymptomatic screening patients. The three malignant cases were seen in patients presenting with a palpable lump (n = 1) or bloody nipple discharge (n = 2). There was a statistically significant association observed between the dilated duct diameter (p = 0.049) and presence of intraductal vascularity (p = 0.0005) with presence of malignancy. CONCLUSION Rate of malignancy is low in solitary dilated ducts, especially among asymptomatic patients. Patient's presenting with clinical symptoms, larger dilated duct diameters, and/or intraductal vascularity may require additional evaluation including biopsy to exclude malignancy. ADVANCES IN KNOWLEDGE Clinical and imaging factors can assist in better identifying patients with solitary dilated ducts who should undergo biopsy.OBJECTIVE For real-time markerless tumour tracking in stereotactic lung radiotherapy, we propose a different approach which uses patient-specific deep learning (DL) using a personalised data generation strategy, avoiding the need for collection of a large patient data set. We validated our strategy with digital phantom simulation and epoxy phantom studies. METHODS We developed lung tumour tracking for radiotherapy using a convolutional neural network trained for each phantom's lesion by using multiple digitally reconstructed radiographs (DRRs) generated from each phantom's treatment planning four-dimensional CT. We trained tumour-bone differentiation using large numbers of training DRRs generated with various projection geometries to simulate tumour motion. We solved the problem of using DRRs for training and X-ray images for tracking using the training DRRs with random contrast transformation and random noise addition. learn more RESULTS We defined adequate tracking accuracy as the percentage frames satisfying less then 1 mm tracking error of the isocentre. In the simulation study, we achieved 100% tracking accuracy in 3 cm spherical and 1.5×2.25×3 cm ovoid masses. In the phantom study, we achieved 100 and 94.7% tracking accuracy in 3 cm and 2 cm spherical masses, respectively. This required 32.5 ms/frame (30.8 fps) real-time processing. CONCLUSIONS We proved the potential feasibility of a real-time markerless tumour tracking framework for stereotactic lung radiotherapy based on patient-specific DL with personalised data generation with digital phantom and epoxy phantom studies. ADVANCES IN KNOWLEDGE Using DL with personalised data generation is an efficient strategy for real-time lung tumour tracking.To test whether high insulin influence the transport of β-alanine into skeletal muscle at either saturating or sub-saturating β-alanine concentrations, we conducted two studies whereby β-alanine and insulin concentrations were controlled. 1) 12 men received supraphysiological amounts of β-alanine intravenously (0.11g·kg·min-1 for 150min) along with insulin infusion or without insulin infusion. β-alanine and carnosine were measured with mass spectrometry in muscle before and 30 min after infusion. Blood samples were taken throughout the infusion protocol for plasma insulin and β-alanine analyses. β-alanine content in 24-h urine was assessed. 2) 6 men ingested typical doses of β-alanine (10mg·kg-1) before insulin infusion or no infusion. β-alanine was assessed in muscle before and after 120 min following the ingestion. In the experiment 1, no differences between conditions were shown for plasma β-alanine, muscle β-alanine, muscle carnosine and urinary β-alanine concentrations (all p>0.05). In the experiment 2, no differences between conditions were shown for plasma β-alanine or muscle β-alanine concentrations (all p>0.05). Hyperinsulinemia did not increase β-alanine uptake by skeletal muscle cells, neither when substrate concentrations exceed the Vmax of β-alanine transporter TauT, nor when it was below saturation. This refutes the notion that β-alanine supplementation alongside meals is necessary to maximise its transport into muscle.OBJECTIVE To evaluate phantomless assessment of volumetric bone mineral density (vBMD) based on virtual non-contrast images of arterial (VNCa) and venous phase (VNCv) derived from spectral detector CT in comparison to true non-contrast (TNC) images and adjusted venous phase conventional images (CIV(adjusted)). METHODS 104 consecutive patients who underwent triphasic spectral detector CT between January 2018 and April 2019 were retrospectively included. TNC, VNCa, VNCv and venous phase images (CIV) were reconstructed. vBMD was obtained by two radiologists using an FDA/CE-cleared software. Average vBMD of the first three lumbar vertebrae was determined in each reconstruction; vBMD of CIV was adjusted for contrast enhancement as suggested earlier. RESULTS vBMD values obtained from CIV(adjusted) are comparable to vBMD values derived from TNC images (91.79 ± 36.52 vs 90.16 ± 41.71 mg/cm3, p = 1.00); however, vBMD values derived from VNCa and VNCv (42.20 ± 22.50 and 41.98 ± 23.3 mg/cm3 respectively) were significantly lower as compared to vBMD values from TNC and CIV(adjusted) (all p ≤ 0.01). CONCLUSION Spectral detector CT-derived virtual non-contrast images systematically underestimate vBMD and therefore should not be used without appropriate adjustments. Adjusted venous phase images provide reliable results and may be utilized for an opportunistic BMD screening in CT examinations. ADVANCES IN KNOWLEDGE Adjustments of venous phase images facilitate opportunistic assessment of vBMD, while spectral detector CT-derived VNC images systematically underestimate vBMD.CONTEXT.— The percentage of pregnant women with advanced maternal age (AMA) has increased during the past several decades due to various socioeconomic factors and advances in assisted reproduction. These pregnancies are associated with adverse maternal and fetal outcomes. However, the underlying placental pathology has not been well described. OBJECTIVE.— To investigate the placental histopathology associated with AMA pregnancies. DESIGN.— Placental pathology from 168 AMA women 35 years or older at delivery was reviewed. The cases were subdivided into two age subgroups, ages 35 to 39 and 40 or older, as well as a "pure AMA" subgroup where the only indication for placental examination was AMA. A group of 60 consecutive non-AMA placentas was also identified and used as comparison. The spectrum of histologic features in each case was catalogued. RESULTS.— Of the overall AMA cases, meconium deposition was seen in 55% (93 of 168), chorangiosis in 40% (68 of 168), and acute chorioamnionitis in 36% (60 of 168). Fetal vascular malperfusion was also seen with high frequency (30%; 50 of 168). Two histologic alterations found to be significantly different between the 35 and 39 and greater than 40 age subgroups were fetal vascular malperfusion (11% [7 of 65] versus 42% [43 of 103]; P = .001) and delayed villous maturation (1.5% [1 of 65] versus 13% [13 of 103]; P = .02). The pure AMA subgroup showed no statistically significant differences compared with the overall AMA group. Chronic deciduitis was the only statistically significant difference between the overall AMA group and the non-AMA comparison group (14% [23 of 168] versus 30% [18 of 60]; P = .02). CONCLUSIONS.— Our findings, particularly the high frequency of fetal vascular malperfusion, suggest that AMA should be an independent indication for placental pathologic examination.CONTEXT.— Apixaban causes a false increase in activated protein C resistance (APCR) ratios and possibly protein S activity. OBJECTIVE.— To investigate whether this increase can mask a diagnosis of factor V Leiden (FVL) or protein S deficiency in an actual population of patients undergoing apixaban treatment and hypercoagulation testing. DESIGN.— During a 4.5-year period involving 58 patients, we compared the following 4 groups heterozygous for FVL (FVL-HET)/taking apixaban, wild-type/taking apixaban, heterozygous for FVL/no apixaban, and normal APCR/no apixaban. Patients taking apixaban were also tested for protein S functional activity and free antigen (n = 40). RESULTS.— FVL-HET patients taking apixaban had lower APCR ratios than wild-type patients (P less then .001). Activated protein C resistance in FVL-HET patients taking apixaban fell more than 3 SD below the cutoff of 2.2 at which the laboratory reflexes FVL DNA testing. No cases of FVL were missed despite apixaban. In contrast to rivaroxaban, apixaban did not interfere with the assessment of protein S activity (mean activity 93.9 IU/dL, free antigen 93.1 IU/dL, P = .39). A total 3 of 40 patients (8%) had low free protein S antigen (30, 55, and 57 IU/dL), with correspondingly similar activity results (27, 59, and 52 IU/dL, respectively). Apixaban did not cause a missed diagnosis of protein S deficiency. CONCLUSIONS.— Despite apixaban treatment, APCR testing can distinguish FVL-HET from healthy patients, rendering indiscriminate FVL DNA testing of all patients on apixaban unnecessary. Apixaban did not affect protein S activity.CONTEXT.— Accurate HER2 testing in breast cancer is crucial for appropriate precision therapy. HER2 testing is most commonly accomplished by a combination of immunohistochemistry and in situ hybridization techniques, as gene amplification is closely tied to protein overexpression. During the last 5+ years, brightfield dual in situ hybridization (DISH) has replaced fluorescence methods (fluorescence in situ hybridization [FISH]) in some laboratories. OBJECTIVE.— To analyze routine HER2 DISH performance in the field. DESIGN.— We reviewed our experience with HER2 DISH performed at outside laboratories and referred for patient care. RESULTS.— Of 273 identified retrospective DISH results, 55 had repeated FISH testing at our institution; 7 (13%) were discordant. Additional cases had technical flaws hampering appropriate scoring. In 23 cases (42%), HER2 DISH was performed without immunohistochemistry. Slide review of a prospective cohort of 42 consecutive DISH cases revealed 14 (33%) with technical or interpretative limitations potentially jeopardizing results.