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Moving beyond regression techniques in cardiovascular risk prediction: applying machine learning to address analytic challenges. European heart journal Risk prediction plays an important role in clinical cardiology research. Traditionally, most risk models have been based on regression models. While useful and robust, these statistical methods are limited to using a small number of predictors which operate in the same way on everyone, and uniformly throughout their range. The purpose of this review is to illustrate the use of machine-learning methods for development of risk prediction models. Typically presented as black box approaches, most machine-learning methods are aimed at solving particular challenges that arise in data analysis that are not well addressed by typical regression approaches. To illustrate these challenges, as well as how different methods can address them, we consider trying to predicting mortality after diagnosis of acute myocardial infarction. We use data derived from our institution's electronic health record and abstract data on 13 regularly measured laboratory markers. We walk through different challenges that arise in modelling these data and then introduce different machine-learning approaches. Finally, we discuss general issues in the application of machine-learning methods including tuning parameters, loss functions, variable importance, and missing data. Overall, this review serves as an introduction for those working on risk modelling to approach the diffuse field of machine learning. 10.1093/eurheartj/ehw302
Microalterations of esophagus in patients with non-erosive reflux disease: in-vivo diagnosis by confocal laser endomicroscopy and its relationship with gastroesophageal reflux. Chu Chuan-Lian,Zhen Yan-Bo,Lv Guo-Ping,Li Chang-Qing,Li Zhen,Qi Qing-Qing,Gu Xiao-Meng,Yu Tao,Zhang Ting-Guo,Zhou Cheng-Jun,Rui-Ji ,Li Yan-Qing The American journal of gastroenterology OBJECTIVES:Objectively diagnosing non-erosive reflux disease (NERD) is still a challenge. We aimed to evaluate the use of in-vivo confocal laser endomicroscopy (CLE) to examine the microalterations of the esophagus in patients with NERD and its relationship with reflux episodes monitored by multiple intraluminal impedance-pH (MII-pH). METHODS:Patients with gastroesophageal reflux symptoms completed reflux disease questionnaires. NERD was determined by negative gastroscopy. Patients without reflux symptoms were recruited as controls. Pilot clinical study was followed by prospective controlled blinded study. All subjects were examined by white-light mode of the endoscopy followed by the standard CLE mode and then MII-pH monitoring. The microalterations seen on CLE images and the correlation between CLE features and reflux episodes were evaluated, the correlation between CLE and transmission electron microscope (TEM) data was also analyzed. RESULTS:On CLE images, NERD patients had more intrapapillary capillary loops (IPCLs) per image than did controls (8.29 ± 3.52 vs. 5.69 ± 2.31, P=0.010), as well as the diameter of IPCLs (19.48 ± 3.13 vs. 15.87 ± 2.21 μm, P=0.041) and intercellular spaces of squamous cells (3.40 ± 0.82 vs. 1.90 ± 0.53 μm, P=0.042). The receiver operating characteristic analysis indicated that IPCLs number (optimal cutoff >6 per image, area under the curve (AUC) 0.722, 95% confidence interval (CI) 0.592-0.853, sensitivity 67.7%, specificity 71.6%), IPCLs diameter (optimal cutoff >17.2 μm, AUC 0.847, 95% CI 0.747-0.947, sensitivity 81%, specificity 76%), and the intercellular spaces of squamous cells (optimal cutoff >2.40 μm, AUC 0.935, 95% CI 0.875-0.995, sensitivity 85.7%, specificity 90.5%) diagnosed NERD with reasonable accuracy. Combined features of dilatation of intercellular space plus increased IPCLs provided 100% specificity in the diagnosis of NERD patients. The intercellular spaces of squamous cells observed on CLE were highly related to that on TEM findings (r=0.75, P<0.001). Multivariate progressive regression analysis showed that acidic reflux, especially in the supine position, was related to the increased number and dilation of IPCLs in the squamous epithelium (β=0.063, t=2.895, P=0.038 and β=0.156, t=1.023, P=0.04). CONCLUSIONS:CLE represents a useful and potentially significant improvement over standard endoscopy to examine the microalterations of the esophagus in vivo. Acidic reflux is responsible for the microalterations in the esophagus of patients with NERD. 10.1038/ajg.2012.44
Effects of various extraocular muscle enlargement patterns on muscle diameter index in graves ophthalmopathy patients: a retrospective cohort study. Scientific reports Graves ophthalmopathy (GO) patients often undergo retrobulbar injection of glucocorticoids (GCs) as a common therapeutic approach. This study aimed to explore the impact of various patterns of extraocular muscle (EOM) enlargement on EOM changes following retrobulbar GCs injection in patients with GO. A retrospective analysis was conducted on GO patients who underwent retrobulbar GCs injections. Data pertaining to EOM diameter (EMD) and muscle diameter index (MDI) were collected from orbital computed tomography (CT) scans. The MDI change (ΔMDI) was calculated by comparing pre- and post-injection MDI values. The relationship between each pre EMD/MDI and ΔMDI was assessed using univariate and multivariate logistic regression analysis. A total of 68 patients with GO were included in this study, accounting for 118 eyes. After retrobulbar injections of GCs, 84 eyes showed a decrease in the MDI, while 34 eyes exhibited an increase in MDI. A threshold effect was observed in the relationship between medial pre EMD/MDI and ΔMDI. When the medial pre EMD/MDI was less than 0.28, a higher medial pre EMD/MDI was associated with a smaller ΔMDI (β = - 25.21, p = 0.0175). However, when the medial pre EMD/MDI was greater than 0.28, no significant association was found between pre EMD/MDI and ΔMDI. There was a negative correlation between medial + lateral pre EMD/MDI and ΔMDI (β = - 11.76, p < 0.0189). A higher medial + lateral pre EMD/MDI was associated with a greater decrease in MDI. Additionally, there was a positive correlation between superior rectus muscle-levator complex (SRLC) pre EMD/MDI and ΔMDI (β = 11.92, p = 0.040). The higher the value of SRLC pre EMD/MDI, the greater the ΔMDI. There was an association between pre EMD/MDI and changes in EOMs after retrobulbar injection of GCs in GO patients. In patients with predominantly enlarged medial rectus muscles and severe degrees of enlargement, retrobulbar injection of GCs should be assessed for its benefit; a combination of medial and lateral rectus muscle enlargement is beneficial for the shrinkage of EOMs following retrobulbar injections; the involvement of the SRLC rectus muscle may be a disadvantageous pattern of shrinkage of EOMs following retrobulbar injections.Trial registration This study is retrospectively registered. We have registered this study with the Chinese Clinical Trials Registry ( www.chictr.org.cn , registration number: ChiCTR2200063429). 10.1038/s41598-023-43942-w
E-cigarette, or vaping, product use associated lung injury (EVALI): case series and diagnostic approach. The Lancet. Respiratory medicine BACKGROUND:Since June, 2019, more than 1000 new cases of e-cigarette, or vaping, product use associated lung injury (EVALI) have been reported in the USA. Patients presented with dyspnoea, cough, and were found to be hypoxaemic with bilateral airspace opacities on chest imaging. Most patients required management in the intensive care unit and steroid therapy. All patients recovered with cessation of vaping, supportive care, and steroid therapy and remained symptom free at follow up. E-cigarette use continues to rapidly escalate in the USA, particularly among youth. METHODS:Cases were defined as patients admitted to the University of Rochester Medical Center (Rochester, NY, USA) who had used e-cigarettes or another vaping device in the 30 days before presentation, and who had bilateral airspace opacification on chest imaging (CT or x-ray). Case details were obtained via medical record review and patient interviews over the past 3 months including symptomatology, physical exam data, imaging studies, laboratory data, vaping history, and subsequent outpatient follow-up data. In collaboration with the New York State Department of Health, our hospital developed a novel clinical practice algorithm based on statewide physician feedback along with input from experts in environmental health, medical toxicology, infectious disease, epidemiology, and chronic disease prevention. FINDINGS:We report 12 cases treated for suspected EVALI at our medical centre between June 6, 2019, and Sept 15, 2019. Ten (83%) patients had dyspnoea, fever, and emesis and nine (75%) had cough. 11 (92%) patients reported the use of e-cigarette cartridges containing tetrahydrocannabinol oil. Although eight (67%) patients required admission to the intensive care unit for hypoxaemic respiratory failure, no deaths occurred. The median hospitalisation duration was 7 days (IQR 7-8). All patients completing follow up (6 [50%]) had resolution of previous chest CT findings and normal spirometry. The clinical algorithm focuses on the key signs and symptoms of EVALI and the importance of ruling out infection and other cardiopulmonary conditions before making a presumptive diagnosis of EVALI. INTERPRETATION:Patients with suspected EVALI in our cohort had life-threatening hypoxaemia, with 67% requiring management in the intensive care unit. Despite the severity of presentation, similar to previous reports of patients with EVALI, most patients improved within 1-2 weeks of initial presentation after vaping cessation and administration of systemic corticosteroids when needed. Almost all (92%) patients with suspected EVALI reported vaping a THC product, making THC containing e-liquids or oils a key focus on the ongoing nationwide investigations into the cause of EVALI. Additional research is required to understand the potential toxins, underlying pathophysiological mechanisms, and identification of susceptible individuals at higher risk for hospitalisation due to EVALI. To our knowledge we present the first clinical practice algorithm for the evaluation and management of EVALI, which will be useful for both acute management and improved accurate reporting of this life-threatening respiratory illness. FUNDING:None. 10.1016/S2213-2600(19)30415-1
A U-shaped association between the LDL-cholesterol to HDL-cholesterol ratio and all-cause mortality in elderly hypertensive patients: a prospective cohort study. Yu Yu,Li Minghui,Huang Xiao,Zhou Wei,Wang Tao,Zhu Lingjuan,Ding Congcong,Tao Yu,Bao Huihui,Cheng Xiaoshu Lipids in health and disease BACKGROUND:The low-density lipoprotein cholesterol/high-density lipoprotein- cholesterol (LDL-C/HDL-C) ratio is an excellent predictor of cardiovascular disease (CVD). However, previous studies linking the LDL-C/HDL-C ratio to mortality have yielded inconsistent results and been limited by short follow-up periods. Therefore, the aim of the present study was to determine whether the LDL-C/HDL-C ratio could be an effective predictor of all-cause mortality in elderly hypertensive patients. METHODS:A total of 6941 hypertensive patients aged 65 years or older who were not treated with lipid-lowering drugs were selected from the Chinese Hypertension Registry for analysis. The endpoint of the study was all-cause mortality. The relationship between the LDL-C/HDL-C ratio and all-cause mortality was determined using multivariate Cox proportional hazards regression, smoothing curve fitting (penalized spline method), subgroup analysis and Kaplan-Meier survival curve analysis. RESULTS:During a median follow-up of 1.72 years, 157 all-cause deaths occurred. A U-shaped association was found between the LDL-C/HDL-C ratio and all-cause mortality. Patients were divided according to the quintiles of the LDL-C/HDL-C ratio. Compared to the reference group (Q3: 1.67-2.10), patients with both lower (Q1 and Q2) and higher (Q4 and Q5) LDL-C/HDL-C ratios had higher all-cause mortality (< 1.67: HR 1.81, 95% CI: 1.08-3.03; ≥2.10: HR 2.00, 95% CI: 1.18-3.39). Compared with the lower and higher LDL-C/HDL-C ratio groups, patients with LDL-C/HDL-C ratios of 1.67-2.10 had a significantly higher survival probability (log-rank P = 0.038). CONCLUSIONS:The results suggest that there is a U-shaped association between the LDL-C/HDL-C ratio and all-cause mortality. Both lower and higher LDL-C/HDL-C ratios were associated with increased all-cause mortality in elderly hypertensive patients. 10.1186/s12944-020-01413-5
Brief Report: Switching to DOR/3TC/TDF Maintains HIV-1 Virologic Suppression Through Week 144 in the DRIVE-SHIFT Trial. Journal of acquired immune deficiency syndromes (1999) BACKGROUND:In the primary analysis of the DRIVE-SHIFT trial, switching to doravirine/lamivudine/tenofovir disoproxil fumarate (DOR/3TC/TDF) maintained suppression of HIV-1 through week 48. Here, we present long-term efficacy and safety outcomes through week 144 of the DRIVE-SHIFT trial. METHODS:This phase 3, randomized, open-label trial evaluated switching from a stable antiretroviral regimen to once-daily DOR/3TC/TDF in adults with HIV-1 suppressed for ≥6 months and no previous virologic failure. Participants switched at day 1 [immediate switch group (ISG); n = 447] or week 24 [delayed switch group (DSG); n = 209]. Nine ISG participants who completed week 48 but did not enter extension-1 were excluded from week 144 efficacy analyses. RESULTS:At week 144, HIV-1 RNA <50 copies/mL was maintained in 80.1% of the ISG (351/438) and 83.7% of the DSG (175/209), while 2.7% (12/438) and 4.8% (10/209), respectively, had HIV-1 RNA ≥50 copies/mL (Food and Drug Administration Snapshot approach). Protocol-defined virologic failure after switch occurred in 2.1% of ISG (9/438) and 3.3% of DSG (7/209); no viral resistance to doravirine was detected in 4 participants with samples available. Reductions in fasting lipids were observed at 24 weeks after switch and maintained through week 144. The mean weight change from switch to week 144 was +1.4 kg for ISG and +1.2 kg for DSG. The most common adverse events were nasopharyngitis (16.2%), headache (12.3%), and diarrhea (9.1%). Overall, 4.1% discontinued because of adverse events, and no deaths occurred. CONCLUSIONS:These results confirm that switching to once-daily DOR/3TC/TDF is a generally well-tolerated option for maintaining viral suppression in adults considering a change in therapy. REGISTRATION:ClinicalTrials.gov NCT02397096. 10.1097/QAI.0000000000002642
Switching to Doravirine/Lamivudine/Tenofovir Disoproxil Fumarate (DOR/3TC/TDF) Maintains HIV-1 Virologic Suppression Through 48 Weeks: Results of the DRIVE-SHIFT Trial. Johnson Margaret,Kumar Princy,Molina Jean-Michel,Rizzardini Giuliano,Cahn Pedro,Bickel Markus,Mallolas Josep,Zhou Yan,Morais Cristiana,Kumar Sushma,Sklar Peter,Hanna George J,Hwang Carey,Greaves Wayne, Journal of acquired immune deficiency syndromes (1999) BACKGROUND:Doravirine is a novel, nonnucleoside reverse transcriptase inhibitor with demonstrated efficacy in treatment-naive adults with HIV-1. METHODS:In this open-label, active-controlled, noninferiority trial, adults with HIV-1 virologically suppressed for ≥6 months on 2 nucleoside reverse transcriptase inhibitors plus a boosted protease inhibitor, boosted elvitegravir, or a non-nucleoside reverse transcriptase inhibitor were randomized (2:1) to switch to once-daily, single-tablet doravirine 100 mg with lamivudine 300 mg and tenofovir disoproxil fumarate 300 mg (DOR/3TC/TDF) or to continue their current therapy (Baseline Regimen) for 24 weeks. The primary endpoint was the proportion of participants with HIV-1 RNA <50 copies/mL (defined by the FDA Snapshot approach), with the primary comparison between DOR/3TC/TDF at week 48 and Baseline Regimen at week 24 and a secondary comparison between the groups at week 24 (noninferiority margin, -8%). RESULTS:Six hundred seventy participants (447 DOR/3TC/TDF, 223 Baseline Regimen) were treated and included in the analyses. At week 24, 93.7% on DOR/3TC/TDF vs 94.6% on Baseline Regimen had HIV-1 RNA <50 copies/mL [difference -0.9 (-4.7 to 3.0)]. At week 48, 90.8% on DOR/3TC/TDF had HIV-1 RNA <50 copies/mL, demonstrating noninferiority vs Baseline Regimen at week 24 [difference -3.8 (-7.9 to 0.3)]. In participants on ritonavir-boosted protease inhibitor at entry, mean reductions in fasting LDL-C and non-HDL-C at week 24 were significantly greater for DOR/3TC/TDF vs Baseline Regimen (P < 0.0001). Adverse events occurred in 68.9% on DOR/3TC/TDF and 52.5% on Baseline Regimen by week 24, leading to treatment discontinuation in 2.5% and 0.4%, respectively. CONCLUSIONS:Switching to once-daily DOR/3TC/TDF is a generally well-tolerated option for maintaining viral suppression in patients considering a change in therapy. REGISTRATION:ClinicalTrials.gov NCT02397096. 10.1097/QAI.0000000000002056
Acute skeletal muscle wasting in critical illness. Puthucheary Zudin A,Rawal Jaikitry,McPhail Mark,Connolly Bronwen,Ratnayake Gamunu,Chan Pearl,Hopkinson Nicholas S,Phadke Rahul,Padhke Rahul,Dew Tracy,Sidhu Paul S,Velloso Cristiana,Seymour John,Agley Chibeza C,Selby Anna,Limb Marie,Edwards Lindsay M,Smith Kenneth,Rowlerson Anthea,Rennie Michael John,Moxham John,Harridge Stephen D R,Hart Nicholas,Montgomery Hugh E JAMA IMPORTANCE:Survivors of critical illness demonstrate skeletal muscle wasting with associated functional impairment. OBJECTIVE:To perform a comprehensive prospective characterization of skeletal muscle wasting, defining the pathogenic roles of altered protein synthesis and breakdown. DESIGN, SETTING, AND PARTICIPANTS:Sixty-three critically ill patients (59% male; mean age: 54.7 years [95% CI, 50.0-59.6 years]) with an Acute Physiology and Chronic Health Evaluation II score of 23.5 (95% CI, 21.9-25.2) were prospectively recruited within 24 hours following intensive care unit (ICU) admission from August 2009 to April 2011 at a university teaching and a community hospital in England. Patients were recruited if older than 18 years and were anticipated to be intubated for longer than 48 hours, to spend more than 7 days in critical care, and to survive ICU stay. MAIN OUTCOMES AND MEASURES:Muscle loss was determined through serial ultrasound measurement of the rectus femoris cross-sectional area (CSA) on days 1, 3, 7, and 10. In a subset of patients, the fiber CSA area was quantified along with the ratio of protein to DNA on days 1 and 7. Histopathological analysis was performed. In addition, muscle protein synthesis, breakdown rates, and respective signaling pathways were characterized. RESULTS:There were significant reductions in the rectus femoris CSA observed at day 10 (−17.7% [95% CI, −25.9% to 8.1%]; P < .001). In the 28 patients assessed by all 3 measurement methods on days 1 and 7, the rectus femoris CSA decreased by 10.3% (95% CI, 6.1% to 14.5%), the fiber CSA by 17.5% (95% CI, 5.8% to 29.3%), and the ratio of protein to DNA by 29.5% (95% CI, 13.4% to 45.6%). Decrease in the rectus femoris CSA was greater in patients who experienced multiorgan failure by day 7 (−15.7%; 95% CI, −27.7% to 11.4%) compared with single organ failure (−3.0%; 95% CI, −5.3% to 2.1%) (P < .001), even by day 3 (−8.7% [95% CI, −59.3% to 50.6%] vs −1.8% [95% CI, −12.3% to 10.5%], respectively; P = .03). Myofiber necrosis occurred in 20 of 37 patients (54.1%). Protein synthesis measured by the muscle protein fractional synthetic rate was depressed in patients on day 1 (0.035%/hour; 95% CI, 0.023% to 0.047%/hour) compared with rates observed in fasted healthy controls (0.039%/hour; 95% CI, 0.029% to 0.048%/hour) (P = .57) and increased by day 7 (0.076% [95% CI, 0.032%-0.120%/hour]; P = .03) to rates associated with fed controls (0.065%/hour [95% CI, 0.049% to 0.080%/hour]; P = .30), independent of nutritional load. Leg protein breakdown remained elevated throughout the study (8.5 [95% CI, 4.7 to 12.3] to 10.6 [95% CI, 6.8 to 14.4] μmol of phenylalanine/min/ideal body weight × 100; P = .40). The pattern of intracellular signaling supported increased breakdown (n = 9, r = −0.83, P = .005) and decreased synthesis (n = 9, r = −0.69, P = .04). CONCLUSIONS AND RELEVANCE:Among these critically ill patients, muscle wasting occurred early and rapidly during the first week of critical illness and was more severe among those with multiorgan failure compared with single organ failure. These findings may provide insights into skeletal muscle wasting in critical illness. 10.1001/jama.2013.278481
Peribulbar injection of glucocorticoids for thyroid-associated ophthalmopathy and factors affecting therapeutic effectiveness: A retrospective cohort study of 386 cases. Wang Yujiao,Du Baixue,Yang Mei,Zhu Yanyan,He Weimin Experimental and therapeutic medicine Thyroid-associated ophthalmopathy (TAO) is common in Graves' disease. However, to date, no standard treatment has been established for TAO. The present study aimed to assess peribulbar injection of corticosteroids for TAO treatment as well as factors affecting therapeutic effectiveness. A retrospective cohort study was performed at West China Hospital, Sichuan University (Chengdu, China). Patients with TAO were administered peribulbar injection of triamcinolone acetonide and dexamethasone monthly. Ocular signs after each injection were assessed until the end of treatment. All patients were followed up for at least six months. Best corrected visual acuity, proptosis values, eye motility assessed by the Hess chart, as well as eyelid width and downward movement were determined. In addition, clinical data were retrospectively reviewed to explore factors affecting therapeutic effectiveness by logistic regression analysis. In the present study, 386 patients with TAO (515 eyes) were evaluated; 71.37% of cases of eyelid swelling were relieved and upper eyelid retraction was improved in 47.58% of affected patients. Eye movement disorders, diplopia and strabismus were all alleviated to varying degrees, with few adverse reactions. Logistic regression analysis demonstrated that therapeutic effectiveness was relatively lower in males [odds ratio (OR)=0.32, P=0.001] and patients with thyroid dysfunction (OR=0.41, P=0.002), and that non-smokers had a higher odds of substantial improvement (OR=4.62, P=0.008). The duration of TAO was not significantly associated with the clinical outcome. Patients with reduced disease severity and elevated clinical activity score exhibited higher effectiveness (all P<0.05). In conclusion, peribulbar injection of corticosteroids is effective in treating mild to moderate TAO, with the therapeutic response affected by gender, smoking and disease severity. 10.3892/etm.2020.8896
Chinese herbal medicine Dengzhan Shengmai capsule as adjunctive treatment for ischemic stroke: A systematic review and meta-analysis of randomized clinical trials. Yang Xiao-Ying,Wang Li-Qiong,Li Jin-Gen,Liang Ning,Wang Ying,Liu Jian-Ping Complementary therapies in medicine OBJECTIVE:The existing eligible randomized controlled trials (RCTs) were critically appraised for the effectiveness and safety of Chinese herbal medicine Dengzhan Shenmai for ischemic stroke. DESIGN:Systematic review and meta-analysis (CRD42016042914, http://www.crd.york.ac.uk/PROSPERO). METHODS:Six electronic databases were searched from inception to May 2016. Risk ratio (RR) and mean difference (MD) with a 95% confidence interval (CI) were used as effect estimates using RevMan 5.3. Meta-analysis was performed where data were available. A summary of finding table was generated by the GRADEpro (version 3.6). RESULTS:We identified 14 RCTs involving 5206 participants. Majority of the included trials were of high risk of bias in methodological quality. For acute ischemic stroke, adding DZSM capsule to conventional therapy achieved higher Barthel Index scores (MD 22.37, 95% CI 21.34-23.40), lower neurological function deficit scores (MD - 3.73, 95% CI -5.27 to -2.19) and lower recurrence rate (RR 0.22, 95% CI 0.10, 0.46). For patients in their convalescence (or sequelae) stage of ischemic stroke, DZSM capsule was superior in improving quality of life (MD 28.8, 95% CI 7.10-50.50) and recurrence rate (RR 0.71, 95% CI 0.51-0.99) compared to placebo. No trials reported serious adverse events. CONCLUSION:DZSM capsule appears to improve neurological function, quality of life, and reduce recurrence rate based on conventional therapy for ischemic stroke. DZSM capsule seems generally safe for clinical application. However, the findings of benefit are inconclusive due to generally weak evidence, and further large, rigorous trials are still warranted. 10.1016/j.ctim.2017.12.004
The add-on effect of dengzhan shengmai capsules on secondary prevention of ischemic stroke: A multicentre, randomised, placebo-controlled clinical trial. Cai Yefeng,Zhang Xiaoyun,Huang Yan,Wang Lixin,Sun Jingbo,Liang Weixiong,Ou Aihua,Yu Baili,Guo Jianwen,Zhao Min,Ni Xiaojia,Chen Shaohong Complementary therapies in medicine OBJECTIVE:The Dengzhan Shengmai (DZSM) capsule is a commercially available type of Chinese herbal medicine frequently administered to improve neurological impairment after stroke. Its ability to prevent recurrent stroke, however, has not been determined. This study therefore evaluated the ability of DZSM as an add-on to conventional secondary preventive agents to prevent recurrent ischemic stroke. METHODS:In this randomised, double-blind, placebo-controlled trial, conducted at 83 hospitals in Mainland China, 3143 patients in 14-180 days after the initial onset of ischemic stroke, were randomly allocated to the DZSM (0.36 g, twice daily for 12 months) or the placebo group. All patients in both groups received standard secondary preventive medications. The primary outcome was the 1-year incidence of stroke. Between group differences were assessed using the Cox proportional hazards model. RESULTS:Intent-to-treat analysis showed that 58 (3.8%) participants in the DZSM group and 82 (5.4%) in the placebo group experienced new stroke events (hazard ratio = 0.70, 95% confidence interval = 0.50-0.98, P = 0.036). The type and incidence of adverse events were similar in the DZSM and placebo groups. CONCLUSIONS:The addition of DZSM capsules to standard secondary preventive agents provides additional benefits after the initial onset of ischemic stroke, reducing recurrent stroke without increasing severe adverse events. However, further study is needed to elucidate the role of DZSM on the updated practice of conventional secondary prevention for ischemic stroke. 10.1016/j.ctim.2019.08.015
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. 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. 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. 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