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    Comparison of different devices to measure the intraocular pressure in thyroid-associated orbitopathy. Kuebler Aylin Garip,Wiecha Caroline,Reznicek Lukas,Klingenstein Annemarie,Halfter Kathrin,Priglinger Siegfried,Hintschich Christoph Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie PURPOSE:To evaluate the correlation of the intraocular pressure measurements (IOP) with non-contact tonometer Corvis Scheimpflug technology (Corvis ST), Goldmann applanation tonometry (GAT), ocular response analyzer (ORA), and iCARE rebound tonometer in patients with thyroid-associated orbitopathy (TAO) and eye-healthy subjects (control group). METHODS:Twenty-nine consecutive patients with TAO (79% female) and 30 eye-healthy subjects (60% female) were included in this prospective, age- and sex-matched study. The IOP measurement with Corvis, ORA, GAT, iCARE, and central corneal thickness (CCT) with Corvis was obtained from all study participants. RESULTS:The mean age of the patients was 51 ± 10 years in patients with TAO and 56 ± 13 years in the control group. The mean IOP measurements with GAT, Corvis, ORA, and iCARE were 15.93 ± 4.42 mmHg, 18.10 ± 7.54 mmHg, 18.40 ± 7.93 mmHg, and 16.61 ± 7.96 mmHg in patients with TAO and 14.52 ± 3.02 mmHg, 14.48 ± 3.38 mmHg, 15.29 ± 4.64 mmHg, and 14.13 ± 3.85 mmHg in the control group (P = 0.157, P = 0.004, P = 0.017, and P = 0.176 respectively). The mean CCT was 547.5 ± 39.2 μm in patients with TAO and 560.8 ± 49.8 μm in the control group ( P= 0.261). CONCLUSIONS:The data collected shows an agreement between the iCARE and GAT IOP measurements in TAO patients and in eye-healthy patients. However, the mean value of IOP measurements with Corvis and ORA was significantly higher in patients with TAO in comparison with the control group (P = 0.044 and P = 0.029 respectively). 10.1007/s00417-019-04367-2
    High-Resolution Magnetic Resonance Imaging Can Reliably Detect Orbital Tumor Recurrence after Enucleation in Children with Retinoblastoma. Sirin Selma,de Jong Marcus C,de Graaf Pim,Brisse Hervé J,Galluzzi Paolo,Maeder Philippe,Bornfeld Norbert,Biewald Eva,Metz Klaus A,Temming Petra,Castelijns Jonas A,Goericke Sophia L, Ophthalmology PURPOSE:Orbital tumor recurrence is a rare but serious complication in children with retinoblastoma, leading to a high risk of metastasis and death. Therefore, we assume that these recurrences have to be detected and treated as early as possible. Preliminary studies used magnetic resonance imaging (MRI) to evaluate postsurgical findings in the orbit. In this study, we assessed the diagnostic accuracy of high-resolution MRI to detect orbital tumor recurrence in children with retinoblastoma in a large study cohort. DESIGN:Consecutive retrospective study (2007-2013) assessing MRI findings after enucleation. PARTICIPANTS:A total of 103 MRI examinations of 55 orbits (50 children, 27 male/23 female, mean age 16.3±12.4 months) with a median time of 8 months (range, 0-93) after enucleation for retinoblastoma. METHODS:High-resolution MRI using orbital surface coils was performed on 1.5 Tesla MRI systems to assess abnormal orbital findings. MAIN OUTCOME MEASURES:Five European experts in retinoblastoma imaging evaluated the MRI examinations regarding the presence of abnormal orbital gadolinium enhancement and judged them as "definitive tumor," "suspicious of tumor," "postsurgical condition/scar formation," or "without pathologic findings." The findings were correlated to histopathology (if available), MRI, and clinical follow-up. RESULTS:Abnormal orbital enhancement was a common finding after enucleation (100% in the first 3 months after enucleation, 64.3% >3 years after enucleation). All histopathologically confirmed tumor recurrences (3 of 55 orbits, 5.5%) were correctly judged as "definitive tumor" in MRI. Two orbits from 2 children rated as "suspicious of tumor" received intravenous chemotherapy without histopathologic confirmation; further follow-up (67 and 47 months) revealed no sign of tumor recurrence. In 90.2%, no tumor was suspected on MRI, which was clinically confirmed during follow-up (median follow-up after enucleation, 45 months; range, 8-126). CONCLUSIONS:High-resolution MRI with orbital surface coils may reliably distinguish between common postsurgical contrast enhancement and orbital tumor recurrence, and therefore may be a useful tool to evaluate orbital tumor recurrence after enucleation in children with retinoblastoma. We recommend high-resolution MRI as a potential screening tool for the orbit in children with retinoblastoma to exclude tumor recurrence, especially in high-risk patients within the critical first 2 years after enucleation. 10.1016/j.ophtha.2015.10.054
    Circulating microRNA miR-323-3p as a biomarker of ectopic pregnancy. Zhao Zhen,Zhao Qiuhong,Warrick Joshua,Lockwood Christina M,Woodworth Alison,Moley Kelle H,Gronowski Ann M Clinical chemistry BACKGROUND:The use of serum human chorionic gonadotropin (hCG) and progesterone to identify patients with ectopic pregnancy (EP) has been shown to have poor clinical utility. Pregnancy-associated circulating microRNAs (miRNAs) have been proposed as potential biomarkers for the diagnosis of pregnancy-associated complications. This proof-of-concept study examined the diagnostic accuracy of various miRNAs to detect EP in an emergency department (ED) setting. METHODS:This study was a retrospective case-control analysis of 89 women who presented to the ED with vaginal bleeding and/or abdominal pain/cramping and received a diagnosis of viable intrauterine pregnancy (VIP), spontaneous abortion (SA), or EP. Serum hCG and progesterone concentrations were measured by immunoassays. The serum concentrations of miRNAs miR-323-3p, miR-517a, miR-519d, and miR-525-3p were measured with TaqMan real-time PCR. Statistical analysis was performed to determine the clinical utility of these biomarkers, both as single markers and as multimarker panels for EP. RESULTS:Concentrations of serum hCG, progesterone, miR-517a, miR-519d, and miR-525-3p were significantly lower in EP and SA cases than in VIP cases (P < 0.01). In contrast, the concentration of miR-323-3p was significantly increased in EP cases, compared with SA and VIP cases (P < 0.01). As a single marker, miR-323-3p had the highest sensitivity of 37.0% (at a fixed specificity of 90%). In comparison, the combined panel of hCG, progesterone, and miR-323-3p yielded the highest sensitivity (77.8%, at a fixed specificity of 90%). A stepwise analysis that used hCG first, added progesterone, and then added miR-323-3p yielded a 96.3% sensitivity and a 72.6% specificity. CONCLUSIONS:Pregnancy-associated miRNAs, especially miR-323-3p, added substantial diagnostic accuracy to a panel including hCG and progesterone for the diagnosis of EP. 10.1373/clinchem.2011.179283
    Pregnancy-associated microRNAs in plasma as potential molecular markers of ectopic pregnancy. Miura Kiyonori,Higashijima Ai,Mishima Hiroyuki,Miura Shoko,Kitajima Michio,Kaneuchi Masanori,Yoshiura Koh-Ichiro,Masuzaki Hideaki Fertility and sterility OBJECTIVE:To investigate cell-free pregnancy-associated microRNAs as molecular markers for the diagnosis of ectopic pregnancy. DESIGN:Laboratory study using human plasma samples. SETTING:Research unit in a university hospital. PATIENT(S):Plasma samples from 18 women with ectopic pregnancies (EP group), 12 women with spontaneous abortion (SA group), and 26 normal women with singleton pregnancies (NP group). INTERVENTION(S):Total RNAs containing small RNA molecules extracted from 1.2 mL of plasma. MAIN OUTCOME MEASURE(S):Plasma concentrations of cell-free microRNAs measured by quantitative real-time reverse-transcriptase polymerase chain reaction. RESULT(S):Plasma concentrations of cell-free pregnancy-associated microRNAs (miR-323-3p, miR-515-3p, miR-517a, miR-517c, and miR-518b) and serum concentration of human chorionic gonadotropin (hCG) were confirmed to have statistically significantly different plasma or serum concentrations in women with EP, SA, or NP. There was no statistically significant difference in the plasma concentrations of cell-free miR-21 between the three groups. By correlation coefficient analysis, no relationship was detected between serum hCG levels and plasma cell-free miR-517c, miR-515-3p, miR-517a, miR-518b, miR-323-3p, or miR-21 levels. Plasma concentrations of cell-free miR-517a could distinguish EP/SA from NP, yielding an area under the curve of 0.9654 (95% confidence interval, 0.9172-1.0). Plasma concentrations of cell-free miR-323-3p could distinguish EP from SA, yielding an area under the curve of 0.7454 (95% confidence interval, 0.5558-0.9349). CONCLUSION(S):Cell-free pregnancy-associated microRNAs have potential as molecular markers of ectopic pregnancy. 10.1016/j.fertnstert.2015.01.041
    MicroRNA-873 is a Potential Serum Biomarker for the Detection of Ectopic Pregnancy. Lu Qi,Yan Qi,Xu Fengying,Li Yuhong,Zhao Wenxia,Wu Chunzhu,Wang Yudong,Lang Xiao Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology BACKGROUND:Ectopic pregnancy (EP) refers to the implantation of the zygote outside the uterine cavity. In clinical practice, the diagnosis of EP relies on a combination of ultrasound findings and serum human chorionic gonadotrophin (hCG) measurements. However, the need for serial hCG measurements increases the risk of tubal rupture and death, underscoring the need to identify biomarkers for the early detection of EP. METHODS:The serum concentrations of 21 microRNAs (miRNAs) associated with pregnancy or with known placental expression, as well as serum hCG and progesterone levels were analyzed 36 patients with viable intrauterine pregnancy (VIP), 30 patients with spontaneous abortion (SA), and 34 patients with EP using specific assay kits and reverse transcription PCR. The diagnostic performance of the different serum markers for detecting EP was analyzed by ROC curve analysis. RESULTS:Five miRNAs were differentially expressed between the three groups, of which miR-873 and miR-223 were significantly lower in EP than in VIP and SA patients and did not change significantly according to gestational age, and miR-323 was significantly higher in EP than in VIP and SA. As a single marker, miR-873 had the highest sensitivity for detecting EP at 61.76% (at a fixed specificity of 90%). In comparison, the combination of hCG, progesterone and miR-873 had the highest sensitivity for detecting EP at 79.41% (at a fixed specificity of 90%). CONCLUSION:Although further validation in large-scale prospective studies is necessary, our results suggest that miR-873 could be a valuable noninvasive and stable biomarker for the early detection of EP. 10.1159/000475946
    Early triage of critically ill COVID-19 patients using deep learning. Liang Wenhua,Yao Jianhua,Chen Ailan,Lv Qingquan,Zanin Mark,Liu Jun,Wong SookSan,Li Yimin,Lu Jiatao,Liang Hengrui,Chen Guoqiang,Guo Haiyan,Guo Jun,Zhou Rong,Ou Limin,Zhou Niyun,Chen Hanbo,Yang Fan,Han Xiao,Huan Wenjing,Tang Weimin,Guan Weijie,Chen Zisheng,Zhao Yi,Sang Ling,Xu Yuanda,Wang Wei,Li Shiyue,Lu Ligong,Zhang Nuofu,Zhong Nanshan,Huang Junzhou,He Jianxing Nature communications The sudden deterioration of patients with novel coronavirus disease 2019 (COVID-19) into critical illness is of major concern. It is imperative to identify these patients early. We show that a deep learning-based survival model can predict the risk of COVID-19 patients developing critical illness based on clinical characteristics at admission. We develop this model using a cohort of 1590 patients from 575 medical centers, with internal validation performance of concordance index 0.894 We further validate the model on three separate cohorts from Wuhan, Hubei and Guangdong provinces consisting of 1393 patients with concordance indexes of 0.890, 0.852 and 0.967 respectively. This model is used to create an online calculation tool designed for patient triage at admission to identify patients at risk of severe illness, ensuring that patients at greatest risk of severe illness receive appropriate care as early as possible and allow for effective allocation of health resources. 10.1038/s41467-020-17280-8
    Association of Skipping Breakfast With Cardiovascular and All-Cause Mortality. Rong Shuang,Snetselaar Linda G,Xu Guifeng,Sun Yangbo,Liu Buyun,Wallace Robert B,Bao Wei Journal of the American College of Cardiology BACKGROUND:Skipping breakfast is common among U.S. adults. Limited evidence suggests that skipping breakfast is associated with atherosclerosis and cardiovascular disease. OBJECTIVES:The authors sought to examine the association of skipping breakfast with cardiovascular and all-cause mortality. METHODS:This is a prospective cohort study of a nationally representative sample of 6,550 adults 40 to 75 years of age who participated in the National Health and Nutrition Examination Survey III 1988 to 1994. Frequency of breakfast eating was reported during an in-house interview. Death and underlying causes of death were ascertained by linkage to death records through December 31, 2011. The associations between breakfast consumption frequency and cardiovascular and all-cause mortality were investigated by using weighted Cox proportional hazards regression models. RESULTS:Among the 6,550 participants (mean age 53.2 years; 48.0% male) in this study, 5.1% never consumed breakfast, 10.9% rarely consumed breakfast, 25.0% consumed breakfast some days, and 59.0% consumed breakfast every day. During 112,148 person-years of follow-up, 2,318 deaths occurred including 619 deaths from cardiovascular disease. After adjustment for age, sex, race/ethnicity, socioeconomic status, dietary and lifestyle factors, body mass index, and cardiovascular risk factors, participants who never consumed breakfast compared with those consuming breakfast everyday had hazard ratios of 1.87 (95% confidence interval: 1.14 to 3.04) for cardiovascular mortality and 1.19 (95% confidence interval: 0.99 to 1.42) for all-cause mortality. CONCLUSIONS:In a nationally representative cohort with 17 to 23 years of follow-up, skipping breakfast was associated with a significantly increased risk of mortality from cardiovascular disease. Our study supports the benefits of eating breakfast in promoting cardiovascular health. 10.1016/j.jacc.2019.01.065
    Speckle tracking quantification of lung sliding for the diagnosis of pneumothorax: a multicentric observational study. Duclos Gary,Bobbia Xavier,Markarian Thibaut,Muller Laurent,Cheyssac Camille,Castillon Sarah,Resseguier Noémie,Boussuges Alain,Volpicelli Giovanni,Leone Marc,Zieleskiewicz Laurent Intensive care medicine PURPOSE:Lung ultrasound is used for the diagnosis of pneumothorax, based on lung sliding abolition which is a qualitative and operator-dependent assessment. Speckle tracking allows the quantification of structure deformation over time by analysing acoustic markers. We aimed to test the ability of speckle tracking technology to quantify lung sliding in a selected cohort of patients and to observe how the technology may help the process of pneumothorax diagnosis. METHODS:We performed retrospectively a pleural speckle tracking analysis on ultrasound loops from patients with pneumothorax. We compared the values measured by two observers from pneumothorax side with contralateral normal lung side. The receiver operating characteristic (ROC) curve was constructed to evaluate the performance of maximal pleural strain to detect the lung sliding abolition. Diagnosis performance and time to diagnosis between B-Mode and speckle tracking technology were compared from a third blinded observer. RESULTS:We analysed 104 ultrasound loops from 52 patients. The area under the ROC curve of the maximal pleural strain value to identify lung sliding abolition was 1.00 [95%CI 1.00; 1.00]. Specificity was 100% [95%CI 93%; 100%] and sensitivity was 100% [95%CI 93%; 100%] with the best cut-off of 4%. Over 104 ultrasound loops, the blinded observer made two errors with B-Mode and none with speckle tracking. The median diagnosis time was 3 [2-5] seconds for B-Mode versus 2 [1-2] seconds for speckle tracking (p = 0.001). CONCLUSION:Speckle tracking technology allows lung sliding quantification and detection of lung sliding abolition in case of pneumothorax on selected ultrasound loops. 10.1007/s00134-019-05710-1
    Development and Validation of a Clinical Risk Score to Predict the Occurrence of Critical Illness in Hospitalized Patients With COVID-19. Liang Wenhua,Liang Hengrui,Ou Limin,Chen Binfeng,Chen Ailan,Li Caichen,Li Yimin,Guan Weijie,Sang Ling,Lu Jiatao,Xu Yuanda,Chen Guoqiang,Guo Haiyan,Guo Jun,Chen Zisheng,Zhao Yi,Li Shiyue,Zhang Nuofu,Zhong Nanshan,He Jianxing, JAMA internal medicine Importance:Early identification of patients with novel coronavirus disease 2019 (COVID-19) who may develop critical illness is of great importance and may aid in delivering proper treatment and optimizing use of resources. Objective:To develop and validate a clinical score at hospital admission for predicting which patients with COVID-19 will develop critical illness based on a nationwide cohort in China. Design, Setting, and Participants:Collaborating with the National Health Commission of China, we established a retrospective cohort of patients with COVID-19 from 575 hospitals in 31 provincial administrative regions as of January 31, 2020. Epidemiological, clinical, laboratory, and imaging variables ascertained at hospital admission were screened using Least Absolute Shrinkage and Selection Operator (LASSO) and logistic regression to construct a predictive risk score (COVID-GRAM). The score provides an estimate of the risk that a hospitalized patient with COVID-19 will develop critical illness. Accuracy of the score was measured by the area under the receiver operating characteristic curve (AUC). Data from 4 additional cohorts in China hospitalized with COVID-19 were used to validate the score. Data were analyzed between February 20, 2020 and March 17, 2020. Main Outcomes and Measures:Among patients with COVID-19 admitted to the hospital, critical illness was defined as the composite measure of admission to the intensive care unit, invasive ventilation, or death. Results:The development cohort included 1590 patients. the mean (SD) age of patients in the cohort was 48.9 (15.7) years; 904 (57.3%) were men. The validation cohort included 710 patients with a mean (SD) age of 48.2 (15.2) years, and 382 (53.8%) were men and 172 (24.2%). From 72 potential predictors, 10 variables were independent predictive factors and were included in the risk score: chest radiographic abnormality (OR, 3.39; 95% CI, 2.14-5.38), age (OR, 1.03; 95% CI, 1.01-1.05), hemoptysis (OR, 4.53; 95% CI, 1.36-15.15), dyspnea (OR, 1.88; 95% CI, 1.18-3.01), unconsciousness (OR, 4.71; 95% CI, 1.39-15.98), number of comorbidities (OR, 1.60; 95% CI, 1.27-2.00), cancer history (OR, 4.07; 95% CI, 1.23-13.43), neutrophil-to-lymphocyte ratio (OR, 1.06; 95% CI, 1.02-1.10), lactate dehydrogenase (OR, 1.002; 95% CI, 1.001-1.004) and direct bilirubin (OR, 1.15; 95% CI, 1.06-1.24). The mean AUC in the development cohort was 0.88 (95% CI, 0.85-0.91) and the AUC in the validation cohort was 0.88 (95% CI, 0.84-0.93). The score has been translated into an online risk calculator that is freely available to the public (http://118.126.104.170/). Conclusions and Relevance:In this study, a risk score based on characteristics of COVID-19 patients at the time of admission to the hospital was developed that may help predict a patient's risk of developing critical illness. 10.1001/jamainternmed.2020.2033
    Comparison of Abbreviated Breast MRI vs Digital Breast Tomosynthesis for Breast Cancer Detection Among Women With Dense Breasts Undergoing Screening. Comstock Christopher E,Gatsonis Constantine,Newstead Gillian M,Snyder Bradley S,Gareen Ilana F,Bergin Jennifer T,Rahbar Habib,Sung Janice S,Jacobs Christina,Harvey Jennifer A,Nicholson Mary H,Ward Robert C,Holt Jacqueline,Prather Andrew,Miller Kathy D,Schnall Mitchell D,Kuhl Christiane K JAMA Importance:Improved screening methods for women with dense breasts are needed because of their increased risk of breast cancer and of failed early diagnosis by screening mammography. Objective:To compare the screening performance of abbreviated breast magnetic resonance imaging (MRI) and digital breast tomosynthesis (DBT) in women with dense breasts. Design, Setting, and Participants:Cross-sectional study with longitudinal follow-up at 48 academic, community hospital, and private practice sites in the United States and Germany, conducted between December 2016 and November 2017 among average-risk women aged 40 to 75 years with heterogeneously dense or extremely dense breasts undergoing routine screening. Follow-up ascertainment of cancer diagnoses was complete through September 12, 2019. Exposures:All women underwent screening by both DBT and abbreviated breast MRI, performed in randomized order and read independently to avoid interpretation bias. Main Outcomes and Measures:The primary end point was the invasive cancer detection rate. Secondary outcomes included sensitivity, specificity, additional imaging recommendation rate, and positive predictive value (PPV) of biopsy, using invasive cancer and ductal carcinoma in situ (DCIS) to define a positive reference standard. All outcomes are reported at the participant level. Pathology of core or surgical biopsy was the reference standard for cancer detection rate and PPV; interval cancers reported until the next annual screen were included in the reference standard for sensitivity and specificity. Results:Among 1516 enrolled women, 1444 (median age, 54 [range, 40-75] years) completed both examinations and were included in the analysis. The reference standard was positive for invasive cancer with or without DCIS in 17 women and for DCIS alone in another 6. No interval cancers were observed during follow-up. Abbreviated breast MRI detected all 17 women with invasive cancer and 5 of 6 women with DCIS. Digital breast tomosynthesis detected 7 of 17 women with invasive cancer and 2 of 6 women with DCIS. The invasive cancer detection rate was 11.8 (95% CI, 7.4-18.8) per 1000 women for abbreviated breast MRI vs 4.8 (95% CI, 2.4-10.0) per 1000 women for DBT, a difference of 7 (95% CI, 2.2-11.6) per 1000 women (exact McNemar P = .002). For detection of invasive cancer and DCIS, sensitivity was 95.7% (95% CI, 79.0%-99.2%) with abbreviated breast MRI vs 39.1% (95% CI, 22.2%-59.2%) with DBT (P = .001) and specificity was 86.7% (95% CI, 84.8%-88.4%) vs 97.4% (95% CI, 96.5%-98.1%), respectively (P < .001). The additional imaging recommendation rate was 7.5% (95% CI, 6.2%-9.0%) with abbreviated breast MRI vs 10.1% (95% CI, 8.7%-11.8%) with DBT (P = .02) and the PPV was 19.6% (95% CI, 13.2%-28.2%) vs 31.0% (95% CI, 17.0%-49.7%), respectively (P = .15). Conclusions and Relevance:Among women with dense breasts undergoing screening, abbreviated breast MRI, compared with DBT, was associated with a significantly higher rate of invasive breast cancer detection. Further research is needed to better understand the relationship between screening methods and clinical outcome. Trial Registration:ClinicalTrials.gov Identifier: NCT02933489. 10.1001/jama.2020.0572