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    Lactobacilli-containing vaginal probiotics to cure or prevent bacterial or fungal vaginal dysbiosis: a systematic review and recommendations for future trial designs. van de Wijgert Jhhm,Verwijs M C BJOG : an international journal of obstetrics and gynaecology BACKGROUND:Vaginal probiotics claiming to cure and/or prevent bacterial and/or fungal vaginal dysbiosis are available on the market but, until recently, did not have to be approved as drugs for human use. OBJECTIVES:We evaluated the impact of vaginal probiotics on bacterial vaginosis (BV) and vulvovaginal candidiasis (VVC) cure and/or recurrence, as well as vaginal microbiota (VMB) composition and vaginal detection of probiotic strains. SEARCH STRATEGY:We performed a systematic literature search in MEDLINE and Embase up to 15 January 2019. SELECTION CRITERIA:There were no restrictions in probiotic strains/formulations, study populations, and designs. BV had to be diagnosed by Nugent or Ison-Hay Gram stain scoring, VVC by culture, wet mount or PCR, and VMB composition/detection by molecular techniques. DATA COLLECTION AND ANALYSIS:The authors independently extracted data. MAIN RESULTS:All 22 vaginal probiotics evaluated in the 34 eligible studies contained Lactobacillus strains, and some contained additional active ingredients. The probiotics hold promise for BV cure and prevention, but much less so for VVC cure and prevention. No major safety concerns were reported in any of the studies. Vaginal detection of probiotic strains never lasted long beyond the dosing period, suggesting that they did not colonise the vagina. However, findings are not definitive because heterogeneity was high and the quality of most studies suboptimal. CONCLUSIONS:Availability of vaginal probiotics for vaginal health indications will likely decline in 2020 because of regulatory changes. We urge the field to invest in clinical evidence-based product development and to conduct future trials more rigorously. TWEETABLE ABSTRACT:Lactobacilli-containing vaginal probiotics hold promise for bacterial vaginosis cure and prevention, but not for vulvovaginal candidiasis. 10.1111/1471-0528.15870
    The prevalence of thyroid nodules in northwest China and its correlation with metabolic parameters and uric acid. Liu Yao,Lin Ziwei,Sheng Chunjun,Zhu Yikun,Huang Yun,Zhong Ni,Jia Zhao,Qu Shen Oncotarget This study aimed to estimate the prevalence of thyroid nodules (TN) and investigate its correlation with metabolic parameters, especially uric acid (UA) in northwest Chinese population. We conducted a large cross-sectional survey with 67,781 residents (33,020 men, 34,761 women), aged from 18 to 86 years in Shanxi, China, from January 2012 to December 2014. A thyroid ultrasound examination was performed with number and size of nodules being recorded. Metabolic parameters including body mass index (BMI), blood pressure (BP), triglycerides (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-c), high-density lipoprotein cholesterol (HDL-c), fasting glucose (FG), and uric acid (UA) were also examined. Our study revealed that approximately 30.7% of men and 39.9% of women in Northwest China had TN, about half of which were multi-nodularity and a quarter of their TN larger than 1 cm. The prevalence of TN increased with aging and increasing BMI, and metabolic disorders, which also related to the increased incident of multi-nodularity and larger TN. Serum UA appeared to be a protective factor for TN in men older than 30 years, but a risk factor in both men younger than 30 years and women older than 30 years. This phenomenon needs to be further investigated. 10.18632/oncotarget.14720
    Retrospective Analysis of the Correlation between Uric Acid and Thyroid Hormone in People with Normal Thyroid Function. Chao Guanqun,Zhu Yue,Fang Lizheng Journal of diabetes research Objective:This study adopts the method of retrospective analysis to collect general information and laboratory results of physical examination population, hoping to clarify the correlation between uric acid and thyroid hormone. Methods:The subjects of the study were healthy subjects who underwent physical examination at the Sir Run Run Shaw Hospital affiliated to the Medical College of Zhejiang University from January 2016 to December 2018. Demographic information and medical history of all subjects were recorded through an electronic health system. Serum uric acid (SUA) was grouped by quartiles. Statistical analyses were performed with R version 3.5.1. Results:A total of 48,526 subjects were included in the analysis. Gender ratio, age, BMI, waist circumference, systolic blood pressure, diastolic blood pressure, FBG, HbA1c, TG, HDL-C, ALT, AST, FT3, FT4, and TSH were significantly different among the uric acid groups. The regression coefficients of SUA in the TSH, FT3, and FT4 regression models were = 1.000 (95% CI 1.000-1.000, = 0.009), = 0.999 (95% CI 0.999-0.999, < 0.001), and = 1.001 (95% CI 1.001-1.001,   < 0.001), respectively. There was a significant dose-dependent relationship between FT4, FT3, and SUA gradient. Conclusions:Under normal thyroid function, there were significant differences in TSH, FT3, and FT4 between groups with different uric acid levels. Uric acid levels were linearly correlated with FT3 and FT4, but not with TSH. 10.1155/2019/5904264
    The Utility of the Random Urine Uric Acid-to-Creatinine Ratio for Patients with Gout Who Need Uricosuric Agents: Retrospective Cross-Sectional Study. Choi Sang Tae,Song Jung Soo,Kim Seung Jun,Kim Chan Ho,Moon Sung Jin Journal of Korean medical science BACKGROUND:The 24-hour uric acid excretion measurement is important in assessing disease status and helping to select the appropriate uric acid-lowering agent for patients with gout, however, it is inconvenient. The authors investigated the efficacy of the random urine uric acid-to-creatinine (UA/CR) ratio to screen the patients who under-secreted 24-hour urine uric acid. METHODS:This was a retrospective cross-sectional study. Ninety patients with gout, without undergoing uric acid-lowering treatment were enrolled. Twenty-four-hour urine and random urine samples were obtained on the same day. Six hundred mg of uric acid in the 24-hour urine sample was used as a standard for distinguishing between over and under-excretion groups. RESULTS:The random urinary UA/CR ratio showed positive correlation with 24-hour urine uric acid excretion (γ = 0.398, < 0.001). All the patients with the random UA/CR less than 0.2 excreted less than 600 mg uric acid in 24-hour urine collection. When the random urine UA/CR ratio < 0.2 was regarded as a positive result, the positive predictive value, negative predictive value, sensitivity, and specificity in the uric acid under-excretion were 100% (8 of 8), 64.6% (53 of 82), 21.6% (8 of 37), and 100% (53 of 53), respectively. CONCLUSION:There is a moderate positive correlation between the random urinary UA/CR ratio and 24-hour urine uric acid excretion, so that UA/CR ratio may not be a good predictor of 24-hour urine uric acid excretion. However, the random urine UA/CR ratio 0.2 can be a useful predictor to screen the gouty patients who need to be treated with uricosuric drugs. 10.3346/jkms.2020.35.e95
    The Lin28/Let-7 system in early human embryonic tissue and ectopic pregnancy. Lozoya Teresa,Domínguez Francisco,Romero-Ruiz Antonio,Steffani Liliana,Martínez Sebastián,Monterde Mercedes,Ferri Blanca,Núñez Maria Jose,AinhoaRomero-Espinós ,Zamora Omar,Gurrea Marta,Sangiao-Alvarellos Susana,Vega Olivia,Simón Carlos,Pellicer Antonio,Tena-Sempere Manuel PloS one Our objective was to determine the expression of the elements of the Lin28/Let-7 system, and related microRNAs (miRNAs), in early stages of human placentation and ectopic pregnancy, as a means to assess the potential role of this molecular hub in the pathogenesis of ectopic gestation. Seventeen patients suffering from tubal ectopic pregnancy (cases) and forty-three women with normal on-going gestation that desired voluntary termination of pregnancy (VTOP; controls) were recruited for the study. Embryonic tissues were subjected to RNA extraction and quantitative PCR analyses for LIN28B, Let-7a, miR-132, miR-145 and mir-323-3p were performed. Our results demonstrate that the expression of LIN28B mRNA was barely detectable in embryonic tissue from early stages of gestation and sharply increased thereafter to plateau between gestational weeks 7-9. In contrast, expression levels of Let-7, mir-132 and mir-145 were high in embryonic tissue from early gestations (≤ 6-weeks) and abruptly declined thereafter, especially for Let-7. Opposite trends were detected for mir-323-3p. Embryonic expression of LIN28B mRNA was higher in early stages (≤ 6-weeks) of ectopic pregnancy than in normal gestation. In contrast, Let-7a expression was significantly lower in early ectopic pregnancies, while miR-132 and miR-145 levels were not altered. Expression of mir-323-3p was also suppressed in ectopic embryonic tissue. We are the first to document reciprocal changes in the expression profiles of the gene encoding the RNA-binding protein, LIN28B, and the related miRNAs, Let-7a, mir-132 and mir-145, in early stages of human placentation. This finding suggests the potential involvement of LIN28B/Let-7 (de)regulated pathways in the pathophysiology of ectopic pregnancy in humans. 10.1371/journal.pone.0087698
    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
    Embryonic miRNA profiles of normal and ectopic pregnancies. Dominguez Francisco,Moreno-Moya Juan Manuel,Lozoya Teresa,Romero Ainhoa,Martínez Sebastian,Monterde Mercedes,Gurrea Marta,Ferri Blanca,Núñez Maria Jose,Simón Carlos,Pellicer Antonio PloS one Our objective was to investigate the miRNA profile of embryonic tissues in ectopic pregnancies (EPs) and controlled abortions (voluntary termination of pregnancy; VTOP). Twenty-three patients suffering from tubal EP and twenty-nine patients with a normal ongoing pregnancy scheduled for a VTOP were recruited. Embryonic tissue samples were analyzed by miRNA microarray and further validated by real time PCR. Microarray studies showed that four miRNAs were differentially downregulated (hsa-mir-196b, hsa-mir-30a, hsa-mir-873, and hsa-mir-337-3p) and three upregulated (hsa-mir-1288, hsa-mir-451, and hsa-mir-223) in EP compared to control tissue samples. Hsa-miR-196, hsa-miR-223, and hsa-miR-451 were further validated by real time PCR in a wider population of EP and control samples. We also performed a computational analysis to identify the gene targets and pathways which might be modulated by these three differentially expressed miRNAs. The most significant pathways found were the mucin type O-glycan biosynthesis and the ECM-receptor-interaction pathways. We also checked that the dysregulation of these three miRNAs was able to alter the expression of the gene targets in the embryonic tissues included in these pathways such as GALNT13 and ITGA2 genes. In conclusion, analysis of miRNAs in ectopic and eutopic embryonic tissues shows different expression patterns that could modify pathways which are critical for correct implantation, providing new insights into the understanding of ectopic implantation in humans. 10.1371/journal.pone.0102185
    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
    Micro-RNA profile and proteins in peritoneal fluid from women with endometriosis: their relationship with sterility. Marí-Alexandre Josep,Barceló-Molina Moisés,Belmonte-López Elisa,García-Oms Javier,Estellés Amparo,Braza-Boïls Aitana,Gilabert-Estellés Juan Fertility and sterility OBJECTIVE:To define the microRNA (miRNA) profile and its relationship with cytokines content in peritoneal fluid (PF) from endometriosis patients. DESIGN:Case-control study. SETTING:University hospital, research institute. PATIENT(S):One hundred twenty-six women with endometriosis (EPF) and 45 control women (CPF). MAIN OUTCOMES MEASURE(S):MiRNA arrays were prepared from six EPF and six CPF. Quantitative reverse transcription-polymerase chain reaction validation of nine selected miRNAs (miR-29c-3p, -106b-3p, -130a-3p, -150-5p, -185-5p, -195-5p, -451a, -486-5p, and -1343-5p) was performed. Vascular endothelial growth factor-A (VEGF-A), thrombospondin-1 (TSP-1), urokinase plasminogen activator (uPA), plasminogen activator inhibitor-1 (PAI-1), matrix metalloproteinase-3 (MMP3), tissue inhibitor of metalloproteinases type 1 (TIMP-1), interleukin (IL)-6, IL-8, IL-17A, macrophage inflammatory protein 1β (MIP1beta), platelet-derived growth factor α-polypeptide A, and regulated on activation, normal T cell expressed and secreted (RANTES) were quantified by ELISA and MILLIPLEX. RESULT(S):MiRNA arrays showed 126 miRNAs differentially expressed (fold change ±1.2) (78 down-regulated, 48 up-regulated) in EPF. Validation showed higher levels of miR-106b-3p, -451a, -486-5p, IL-6, IL-8, uPA, and TIMP-1 in EPF. In menstrual phase, EPF presented up-regulation of miR-106b-3p, -130a-3p, -150-5p, -185-5p, -451a, -486-5p, VEGF-A, IL-8, MIF 1β, uPA, and PAI-1 compared with other phases; however, CPF did not. MiRNA-486-5p was up-regulated in sterile EPF compared with sterile controls, and VEGF-A, IL-8, and TIMP-1 were increased in sterile and fertile EPF compared with fertile CPF. CONCLUSION(S):MiRNAs seem to be involved in the peritoneal alterations in endometriosis, suggesting new mechanisms by which ectopic lesions could implant in endometriosis patients; and to serve as biomarkers for fertility outcome prediction. 10.1016/j.fertnstert.2017.11.036
    Deregulation of miR-324/KISS1/kisspeptin in early ectopic pregnancy: mechanistic findings with clinical and diagnostic implications. Romero-Ruiz Antonio,Avendaño Maria S,Dominguez Francisco,Lozoya Teresa,Molina-Abril Helena,Sangiao-Alvarellos Susana,Gurrea Marta,Lara-Chica Maribel,Fernandez-Sanchez Manuel,Torres-Jimenez Encarnación,Perdices-Lopez Cecilia,Abbara Ali,Steffani Liliana,Calzado Marco A,Dhillo Waljit S,Pellicer Antonio,Tena-Sempere Manuel American journal of obstetrics and gynecology BACKGROUND:Ectopic pregnancy is a life-threatening condition for which novel screening tools that would enable early accurate diagnosis would improve clinical outcomes. Kisspeptins, encoded by KISS1, play an essential role in human reproduction, at least partially by regulating placental function and possibly embryo implantation. Kisspeptin levels are elevated massively in normal pregnancy and reportedly altered in various gestational pathologic diseases. Yet, the pathophysiologic role of KISS1/kisspeptin in ectopic pregnancy has not been investigated previously. OBJECTIVE:The purpose of this study was to evaluate changes of KISS1/kisspeptin levels in ectopic pregnancy and their underlaying molecular mechanisms and to ascertain the diagnostic implications of these changes. STUDY DESIGN:A total of 122 women with normal pregnancy who underwent voluntary termination of pregnancy and 84 patients who experienced tubal ectopic pregnancy were recruited. Measurements of plasma kisspeptins and KISS1 expression analyses in human embryonic/placental tissue were conducted in ectopic pregnancy and voluntary termination of pregnancy control subjects during the early gestational window (<12 weeks). Putative microRNA regulators of KISS1 were predicted in silico, followed by expression analyses of selected microRNAs and validation of repressive interactions in vitro. Circulating levels of these microRNAs were also assayed in ectopic pregnancy vs voluntary termination of pregnancy. RESULTS:Circulating kisspeptins gradually increased during the first trimester of normal pregnancy but were reduced markedly in ectopic pregnancy. This profile correlated with the expression levels of KISS1 in human embryonic/placental tissue, which increased in voluntary termination of pregnancy but remained suppressed in ectopic pregnancy. Bioinformatic predictions and expression analyses identified miR-27b-3p and miR-324-3p as putative repressors of KISS1 in human embryonic/placental tissue at <12 weeks gestation, when expression of microRNAs was low in voluntary termination of pregnancy control subjects but significantly increased in ectopic pregnancy. Yet, a significant repressive interaction was documented only for miR-324-3p, occurring at the predicted 3'-UTR of KISS1. Interestingly, circulating levels of miR-324-3p, but not of miR-27b-3p, were suppressed distinctly in ectopic pregnancy, despite elevated tissue expression of the pre-microRNA. A decision-tree model that used kisspeptin and miR-324-3p levels was successful in discriminating ectopic pregnancy vs voluntary termination of pregnancy, with a receiver-operating characteristic area under the curve of 0.95±0.02 (95% confidence interval). CONCLUSION:Our results document a significant down-regulation of KISS1/kisspeptins in early stages of ectopic pregnancy via, at least partially, a repressive interaction with miR-324-3p. Our data identify circulating kisspeptins and miR-324-3p as putative biomarkers for accurate screening of ectopic pregnancy at early gestational ages. 10.1016/j.ajog.2019.01.228
    Associations of noniodized salt and thyroid nodule among the Chinese population: a large cross-sectional study. Chen Zexin,Xu Weimin,Huang Yangmei,Jin Xingyi,Deng Jin,Zhu Sujuan,Liu Hui,Zhang Shanchun,Yu Yunxian The American journal of clinical nutrition BACKGROUND:The controversy that iodized salt may increase the risk of thyroid disorders has arisen in China during the past several years. OBJECTIVE:This study aimed to explore whether iodized salt increased the risk of thyroid nodule among a Chinese population. DESIGN:A cross-sectional study was conducted in Hangzhou, China, in 2010. Iodized salt intake, urinary iodine concentration (UIC), and thyroid nodule (by ultrasonography) were measured in 9412 adults. The associations of iodized salt with thyroid nodule were evaluated by using multiple mixed logistic regression models. RESULTS:The prevalence of thyroid nodule among men and women was 24.1% and 34.7%, respectively. Adults consuming noniodized salt had an increased risk of thyroid nodule (OR: 1.36; 95% CI: 1.01, 1.83). Similarly, compared with moderate salt appetite, mild salt appetite was associated with an increased risk of thyroid nodule among all adults (OR: 1.19; 95% CI: 1.03, 1.37) and among women (OR: 1.23; 95% CI: 1.03, 1.46). Furthermore, those who consumed neither iodized salt nor milk had a higher risk of thyroid nodule (OR: 1.72; 95% CI: 1.21, 2.43) than did those who consumed both iodized salt and milk. In addition, an increased risk of thyroid nodule (OR: 1.25; 95% CI: 1.07, 1.45) was observed among both pooled samples and women with low UIC. CONCLUSIONS:These findings indicate that low iodine intake may increase the risk of thyroid nodule in a Chinese population, particularly in women. Hence, the Universal Salt Iodization program may be indispensable for a coastal Chinese population such as that living in Hangzhou. This trial was registered at clinicaltrials.gov as NCT01838629. 10.3945/ajcn.112.054353
    Risk Factors Associated With Acute Respiratory Distress Syndrome and Death in Patients With Coronavirus Disease 2019 Pneumonia in Wuhan, China. Wu Chaomin,Chen Xiaoyan,Cai Yanping,Xia Jia'an,Zhou Xing,Xu Sha,Huang Hanping,Zhang Li,Zhou Xia,Du Chunling,Zhang Yuye,Song Juan,Wang Sijiao,Chao Yencheng,Yang Zeyong,Xu Jie,Zhou Xin,Chen Dechang,Xiong Weining,Xu Lei,Zhou Feng,Jiang Jinjun,Bai Chunxue,Zheng Junhua,Song Yuanlin JAMA internal medicine Importance:Coronavirus disease 2019 (COVID-19) is an emerging infectious disease that was first reported in Wuhan, China, and has subsequently spread worldwide. Risk factors for the clinical outcomes of COVID-19 pneumonia have not yet been well delineated. Objective:To describe the clinical characteristics and outcomes in patients with COVID-19 pneumonia who developed acute respiratory distress syndrome (ARDS) or died. Design, Setting, and Participants:Retrospective cohort study of 201 patients with confirmed COVID-19 pneumonia admitted to Wuhan Jinyintan Hospital in China between December 25, 2019, and January 26, 2020. The final date of follow-up was February 13, 2020. Exposures:Confirmed COVID-19 pneumonia. Main Outcomes and Measures:The development of ARDS and death. Epidemiological, demographic, clinical, laboratory, management, treatment, and outcome data were also collected and analyzed. Results:Of 201 patients, the median age was 51 years (interquartile range, 43-60 years), and 128 (63.7%) patients were men. Eighty-four patients (41.8%) developed ARDS, and of those 84 patients, 44 (52.4%) died. In those who developed ARDS, compared with those who did not, more patients presented with dyspnea (50 of 84 [59.5%] patients and 30 of 117 [25.6%] patients, respectively [difference, 33.9%; 95% CI, 19.7%-48.1%]) and had comorbidities such as hypertension (23 of 84 [27.4%] patients and 16 of 117 [13.7%] patients, respectively [difference, 13.7%; 95% CI, 1.3%-26.1%]) and diabetes (16 of 84 [19.0%] patients and 6 of 117 [5.1%] patients, respectively [difference, 13.9%; 95% CI, 3.6%-24.2%]). In bivariate Cox regression analysis, risk factors associated with the development of ARDS and progression from ARDS to death included older age (hazard ratio [HR], 3.26; 95% CI 2.08-5.11; and HR, 6.17; 95% CI, 3.26-11.67, respectively), neutrophilia (HR, 1.14; 95% CI, 1.09-1.19; and HR, 1.08; 95% CI, 1.01-1.17, respectively), and organ and coagulation dysfunction (eg, higher lactate dehydrogenase [HR, 1.61; 95% CI, 1.44-1.79; and HR, 1.30; 95% CI, 1.11-1.52, respectively] and D-dimer [HR, 1.03; 95% CI, 1.01-1.04; and HR, 1.02; 95% CI, 1.01-1.04, respectively]). High fever (≥39 °C) was associated with higher likelihood of ARDS development (HR, 1.77; 95% CI, 1.11-2.84) and lower likelihood of death (HR, 0.41; 95% CI, 0.21-0.82). Among patients with ARDS, treatment with methylprednisolone decreased the risk of death (HR, 0.38; 95% CI, 0.20-0.72). Conclusions and Relevance:Older age was associated with greater risk of development of ARDS and death likely owing to less rigorous immune response. Although high fever was associated with the development of ARDS, it was also associated with better outcomes among patients with ARDS. Moreover, treatment with methylprednisolone may be beneficial for patients who develop ARDS. 10.1001/jamainternmed.2020.0994
    Coronavirus in pregnancy and delivery: rapid review. Mullins E,Evans D,Viner R M,O'Brien P,Morris E Ultrasound in obstetrics & gynecology : the official journal of the International Society of Ultrasound in Obstetrics and Gynecology OBJECTIVES:There are limited case series reporting the impact on women affected by coronavirus during pregnancy. In women affected by severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS), the case fatality rate appears higher in those affected in pregnancy compared with non-pregnant women. We conducted a rapid review to guide health policy and management of women affected by COVID-19 during pregnancy, which was used to develop the Royal College of Obstetricians and Gynaecologists' (RCOG) guidelines on COVID-19 infection in pregnancy. METHODS:Searches were conducted in PubMed and MedRxiv to identify primary case reports, case series, observational studies and randomized controlled trials describing women affected by coronavirus in pregnancy. Data were extracted from relevant papers. This review has been used to develop guidelines with representatives of the Royal College of Paediatrics and Child Health (RCPCH) and RCOG who provided expert consensus on areas in which data were lacking. RESULTS:From 9965 search results in PubMed and 600 in MedRxiv, 21 relevant studies, all of which were case reports or case series, were identified. From reports of 32 women to date affected by COVID-19 in pregnancy, delivering 30 babies (one set of twins, three ongoing pregnancies), seven (22%) were asymptomatic and two (6%) were admitted to the intensive care unit (ICU), one of whom remained on extracorporeal membrane oxygenation. No maternal deaths have been reported to date. Delivery was by Cesarean section in 27 cases and by vaginal delivery in two, and 15 (47%) delivered preterm. There was one stillbirth and one neonatal death. In 25 babies, no cases of vertical transmission were reported; 15 were reported as being tested with reverse transcription polymerase chain reaction after delivery. Case fatality rates for SARS and MERS were 15% and 27%, respectively. SARS was associated with miscarriage or intrauterine death in five cases, and fetal growth restriction was noted in two ongoing pregnancies affected by SARS in the third trimester. CONCLUSIONS:Serious morbidity occurred in 2/32 women with COVID-19, both of whom required ICU care. Compared with SARS and MERS, COVID-19 appears less lethal, acknowledging the limited number of cases reported to date and that one woman remains in a critical condition. Preterm delivery affected 47% of women hospitalized with COVID-19, which may put considerable pressure on neonatal services if the UK's reasonable worst-case scenario of 80% of the population being affected is realized. Based on this review, RCOG, in consultation with RCPCH, developed guidance for delivery and neonatal care in pregnancies affected by COVID-19, which recommends that delivery mode be determined primarily by obstetric indication and recommends against routine separation of affected mothers and their babies. We hope that this review will be helpful for maternity and neonatal services planning their response to COVID-19. © 2020 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of the International Society of Ultrasound in Obstetrics and Gynecology. 10.1002/uog.22014
    Association of Cardiac Injury With Mortality in Hospitalized Patients With COVID-19 in Wuhan, China. Shi Shaobo,Qin Mu,Shen Bo,Cai Yuli,Liu Tao,Yang Fan,Gong Wei,Liu Xu,Liang Jinjun,Zhao Qinyan,Huang He,Yang Bo,Huang Congxin JAMA cardiology Importance:Coronavirus disease 2019 (COVID-19) has resulted in considerable morbidity and mortality worldwide since December 2019. However, information on cardiac injury in patients affected by COVID-19 is limited. Objective:To explore the association between cardiac injury and mortality in patients with COVID-19. Design, Setting, and Participants:This cohort study was conducted from January 20, 2020, to February 10, 2020, in a single center at Renmin Hospital of Wuhan University, Wuhan, China; the final date of follow-up was February 15, 2020. All consecutive inpatients with laboratory-confirmed COVID-19 were included in this study. Main Outcomes and Measures:Clinical laboratory, radiological, and treatment data were collected and analyzed. Outcomes of patients with and without cardiac injury were compared. The association between cardiac injury and mortality was analyzed. Results:A total of 416 hospitalized patients with COVID-19 were included in the final analysis; the median age was 64 years (range, 21-95 years), and 211 (50.7%) were female. Common symptoms included fever (334 patients [80.3%]), cough (144 [34.6%]), and shortness of breath (117 [28.1%]). A total of 82 patients (19.7%) had cardiac injury, and compared with patients without cardiac injury, these patients were older (median [range] age, 74 [34-95] vs 60 [21-90] years; P < .001); had more comorbidities (eg, hypertension in 49 of 82 [59.8%] vs 78 of 334 [23.4%]; P < .001); had higher leukocyte counts (median [interquartile range (IQR)], 9400 [6900-13 800] vs 5500 [4200-7400] cells/μL) and levels of C-reactive protein (median [IQR], 10.2 [6.4-17.0] vs 3.7 [1.0-7.3] mg/dL), procalcitonin (median [IQR], 0.27 [0.10-1.22] vs 0.06 [0.03-0.10] ng/mL), creatinine kinase-myocardial band (median [IQR], 3.2 [1.8-6.2] vs 0.9 [0.6-1.3] ng/mL), myohemoglobin (median [IQR], 128 [68-305] vs 39 [27-65] μg/L), high-sensitivity troponin I (median [IQR], 0.19 [0.08-1.12] vs <0.006 [<0.006-0.009] μg/L), N-terminal pro-B-type natriuretic peptide (median [IQR], 1689 [698-3327] vs 139 [51-335] pg/mL), aspartate aminotransferase (median [IQR], 40 [27-60] vs 29 [21-40] U/L), and creatinine (median [IQR], 1.15 [0.72-1.92] vs 0.64 [0.54-0.78] mg/dL); and had a higher proportion of multiple mottling and ground-glass opacity in radiographic findings (53 of 82 patients [64.6%] vs 15 of 334 patients [4.5%]). Greater proportions of patients with cardiac injury required noninvasive mechanical ventilation (38 of 82 [46.3%] vs 13 of 334 [3.9%]; P < .001) or invasive mechanical ventilation (18 of 82 [22.0%] vs 14 of 334 [4.2%]; P < .001) than those without cardiac injury. Complications were more common in patients with cardiac injury than those without cardiac injury and included acute respiratory distress syndrome (48 of 82 [58.5%] vs 49 of 334 [14.7%]; P < .001), acute kidney injury (7 of 82 [8.5%] vs 1 of 334 [0.3%]; P < .001), electrolyte disturbances (13 of 82 [15.9%] vs 17 of 334 [5.1%]; P = .003), hypoproteinemia (11 of 82 [13.4%] vs 16 of 334 [4.8%]; P = .01), and coagulation disorders (6 of 82 [7.3%] vs 6 of 334 [1.8%]; P = .02). Patients with cardiac injury had higher mortality than those without cardiac injury (42 of 82 [51.2%] vs 15 of 334 [4.5%]; P < .001). In a Cox regression model, patients with vs those without cardiac injury were at a higher risk of death, both during the time from symptom onset (hazard ratio, 4.26 [95% CI, 1.92-9.49]) and from admission to end point (hazard ratio, 3.41 [95% CI, 1.62-7.16]). Conclusions and Relevance:Cardiac injury is a common condition among hospitalized patients with COVID-19 in Wuhan, China, and it is associated with higher risk of in-hospital mortality. 10.1001/jamacardio.2020.0950
    Long-term effect of thymectomy plus prednisone versus prednisone alone in patients with non-thymomatous myasthenia gravis: 2-year extension of the MGTX randomised trial. Wolfe Gil I,Kaminski Henry J,Aban Inmaculada B,Minisman Greg,Kuo Hui-Chien,Marx Alexander,Ströbel Philipp,Mazia Claudio,Oger Joel,Cea J Gabriel,Heckmann Jeannine M,Evoli Amelia,Nix Wilfred,Ciafaloni Emma,Antonini Giovanni,Witoonpanich Rawiphan,King John O,Beydoun Said R,Chalk Colin H,Barboi Alexandru C,Amato Anthony A,Shaibani Aziz I,Katirji Bashar,Lecky Bryan R F,Buckley Camilla,Vincent Angela,Dias-Tosta Elza,Yoshikawa Hiroaki,Waddington-Cruz Márcia,Pulley Michael T,Rivner Michael H,Kostera-Pruszczyk Anna,Pascuzzi Robert M,Jackson Carlayne E,Verschuuren Jan J G M,Massey Janice M,Kissel John T,Werneck Lineu C,Benatar Michael,Barohn Richard J,Tandan Rup,Mozaffar Tahseen,Silvestri Nicholas J,Conwit Robin,Sonett Joshua R,Jaretzki Alfred,Newsom-Davis John,Cutter Gary R, The Lancet. Neurology BACKGROUND:The Thymectomy Trial in Non-Thymomatous Myasthenia Gravis Patients Receiving Prednisone (MGTX) showed that thymectomy combined with prednisone was superior to prednisone alone in improving clinical status as measured by the Quantitative Myasthenia Gravis (QMG) score in patients with generalised non-thymomatous myasthenia gravis at 3 years. We investigated the long-term effects of thymectomy up to 5 years on clinical status, medication requirements, and adverse events. METHODS:We did a rater-blinded 2-year extension study at 36 centres in 15 countries for all patients who completed the randomised controlled MGTX and were willing to participate. MGTX patients were aged 18 to 65 years at enrolment, had generalised non-thymomatous myasthenia gravis of less than 5 years' duration, had acetylcholine receptor antibody titres of 1·00 nmol/L or higher (or concentrations of 0·50-0·99 nmol/L if diagnosis was confirmed by positive edrophonium or abnormal repetitive nerve stimulation, or abnormal single fibre electromyography), had Myasthenia Gravis Foundation of America Clinical Classification Class II-IV disease, and were on optimal anticholinesterase therapy with or without oral corticosteroids. In MGTX, patients were randomly assigned (1:1) to either thymectomy plus prednisone or prednisone alone. All patients in both groups received oral prednisone at doses titrated up to 100 mg on alternate days until they achieved minimal manifestation status. The primary endpoints of the extension phase were the time-weighted means of the QMG score and alternate-day prednisone dose from month 0 to month 60. Analyses were by intention to treat. The trial is registered with ClinicalTrials.gov, number NCT00294658. It is closed to new participants, with follow-up completed. FINDINGS:Of the 111 patients who completed the 3-year MGTX, 68 (61%) entered the extension study between Sept 1, 2009, and Aug 26, 2015 (33 in the prednisone alone group and 35 in the prednisone plus thymectomy group). 50 (74%) patients completed the 60-month assessment, 24 in the prednisone alone group and 26 in the prednisone plus thymectomy group. At 5 years, patients in the thymectomy plus prednisone group had significantly lower time-weighted mean QMG scores (5·47 [SD 3·87] vs 9·34 [5·08]; p=0·0007) and mean alternate-day prednisone doses (24 mg [SD 21] vs 48 mg [29]; p=0·0002) than did those in the prednisone alone group. 14 (42%) of 33 patients in the prednisone group, and 12 (34%) of 35 in the thymectomy plus prednisone group, had at least one adverse event by month 60. No treatment-related deaths were reported during the extension phase. INTERPRETATION:At 5 years, thymectomy plus prednisone continues to confer benefits in patients with generalised non-thymomatous myasthenia gravis compared with prednisone alone. Although caution is appropriate when generalising our findings because of the small sample size of our study, they nevertheless provide further support for the benefits of thymectomy in patients with generalised non-thymomatous myasthenia gravis. FUNDING:National Institutes of Health, National Institute of Neurological Disorders and Stroke. 10.1016/S1474-4422(18)30392-2
    Effect of thymectomy in elderly patients with non-thymomatous generalized myasthenia gravis. Kim Seung Woo,Choi Young-Chul,Kim Seung Min,Shim Hyo Sup,Shin Ha Young Journal of neurology Whether thymectomy is beneficial in elderly patients with myasthenia gravis (MG) is unclear. Thus, we assessed whether conducting thymectomy in MG patients aged ≥ 50 years is beneficial. This retrospective cohort study included patients with MG between 1990 and 2018. Thymectomy and control cohorts were selected from among the population of MG patients with an age at onset of ≥ 45 years and elevated concentrations of acetylcholine-receptor antibodies. Patients with evidence of thymic malignancy were excluded. Of these patients, those who underwent thymectomy at the age of ≥ 50 years were designated as the thymectomy group and those who received only medical treatment were designated as the medical treatment group. We compared the Myasthenia Gravis Foundation of America post-intervention status between the thymectomy and medical treatment groups. Landmark analysis was conducted with the landmark set at 24 months. A total of 34 and 105 patients were classified into the thymectomy and medical treatment groups, respectively. Before landmark analysis, the thymectomy group had a higher cumulative incidence of pharmacologic remission (p = 0.009) and complete stable remission (p = 0.022) than the medical treatment group. After landmark analysis, the thymectomy group had a 2.22-fold (95% confidence interval 1.01-4.80) increased chance of achieving pharmacologic remission compared to the medical treatment group after adjustment for age, sex, and disease severity. No significant difference was observed in the rate of relapse after pharmacological remission between the thymectomy (16.7%) and medical treatment groups (21.4%). In conclusion, thymectomy may have a beneficial effect in elderly patients with non-thymomatous generalized MG. 10.1007/s00415-019-09222-2
    United States Multicenter Clinical Trial of Corneal Collagen Crosslinking for Keratoconus Treatment. Hersh Peter S,Stulting R Doyle,Muller David,Durrie Daniel S,Rajpal Rajesh K, Ophthalmology PURPOSE:To evaluate the safety and efficacy of corneal collagen crosslinking (CXL) for the treatment of progressive keratoconus. DESIGN:Prospective, randomized, multicenter, controlled clinical trial. PARTICIPANTS:Patients with progressive keratoconus (n = 205). METHODS:The treatment group underwent standard CXL and the sham control group received riboflavin alone without removal of the epithelium. MAIN OUTCOME MEASURES:The primary efficacy criterion was the change over 1 year of topography-derived maximum keratometry value, comparing treatment with control group. Secondary outcomes evaluated were corrected distance visual acuity (CDVA), uncorrected distance visual acuity (UDVA), manifest refraction spherical equivalent, endothelial cell count, and adverse events. RESULTS:In the CXL treatment group, the maximum keratometry value decreased by 1.6 diopters (D) from baseline to 1 year, whereas keratoconus continued to progress in the control group. In the treatment group, the maximum keratometry value decreased by 2.0 D or more in 28 eyes (31.5%) and increased by 2.0 D or more in 5 eyes (5.6%). The CDVA improved by an average of 5.7 logarithm of the minimum angle of resolution (logMAR) units. Twenty-three eyes (27.7%) gained and 5 eyes lost (6.0%) 10 logMAR or more. The UDVA improved 4.4 logMAR. Corneal haze was the most frequently reported CXL-related adverse finding. There were no significant changes in endothelial cell count 1 year after treatment. CONCLUSIONS:Corneal collagen crosslinking was effective in improving the maximum keratometry value, CDVA, and UCVA in eyes with progressive keratoconus 1 year after treatment, with an excellent safety profile. Corneal collagen crosslinking affords the keratoconic patient an important new option to decrease progression of this ectatic corneal process. 10.1016/j.ophtha.2017.03.052
    Evaluation of keratoconus progression. Shajari Mehdi,Steinwender Gernot,Herrmann Kim,Kubiak Kate Barbara,Pavlovic Ivana,Plawetzki Elena,Schmack Ingo,Kohnen Thomas The British journal of ophthalmology AIM:To define variables for the evaluation of keratoconus progression and to determine cut-off values. METHODS:In this retrospective cohort study (2010-2016), 265 eyes of 165 patients diagnosed with keratoconus underwent two Scheimpflug measurements (Pentacam) that took place 1 year apart ±3 months. Variables used for keratoconus detection were evaluated for progression and a correlation analysis was performed. By logistic regression analysis, a keratoconus progression index (KPI) was defined. Receiver-operating characteristic curve (ROC) analysis was performed and Youden Index calculated to determine cut-off values. RESULTS:Variables used for keratoconus detection showed a weak correlation with each other (eg, correlation r=0.245 between RPImin and Kmax, p<0.001). Therefore, we used parameters that took several variables into consideration (eg, D-index, index of surface variance, index for height asymmetry, KPI). KPI was defined by logistic regression and consisted of a Pachymin coefficient of -0.78 (p=0.001), a maximum elevation of back surface coefficient of 0.27 and coefficient of corneal curvature at the zone 3 mm away from the thinnest point on the posterior corneal surface of -12.44 (both p<0.001). The two variables with the highest Youden Index in the ROC analysis were D-index and KPI: D-index had a cut-off of 0.4175 (70.6% sensitivity) and Youden Index of 0.606. Cut-off for KPI was -0.78196 (84.7% sensitivity) and a Youden Index of 0.747; both 90% specificity. CONCLUSIONS:Keratoconus progression should be defined by evaluating parameters that consider several corneal changes; we suggest D-index and KPI to detect progression. 10.1136/bjophthalmol-2017-311651