The Modular Synthesis of Sulfondiimidoyl Fluorides and their Application to Sulfondiimidamide and Sulfondiimine Synthesis.

A modular synthesis of sulfondiimidoyl fluorides-the double aza-analogues of sulfonyl fluorides-allowing variation of the carbon and both nitrogen-substituents is reported. The chemistry uses readily available organometallic reagents, commercial sulfinylamines, simple electrophiles, and N-fluorobenzenesulfonimide (NFSI), as the starting materials. The reactions are broad in scope, efficient, and scalable. We show that the sulfondiimidoyl fluoride products can be combined with amines to provide sulfondiimidamides, and with organolithium reagents to provide sulfondiimines, and that reactivity in these transformations can be modulated by variation of the N-substituents.

Friedel-Crafts Reactivity with Sulfondiimidoyl Fluorides for the Synthesis of Heteroaryl Sulfondiimines.

Sulfur functional groups are ubiquitous in molecules used in the pharmaceutical and agrochemical industries, and within these collections sulfones hold a prominent position. The double aza-analogues of sulfones, sulfondiimines, offer significant potential in discovery chemistry but to date their applications have been limited by the lack of convenient synthetic routes. The existing methods mainly rely on imination of low-valent-sulfur intermediates, or the combination of pre-formed organometallic reagents and electrophilic S(VI)-functionalities. Herein, we describe a Friedel-Crafts-type reaction of sulfondiimidoyl fluorides with (hetero)aryls. This new SuFEx reactivity benefits from broad functional group tolerance, mild reaction conditions, and does not require the use of pre-formed organometallic reagents. The efficient use of unprotected indoles and pyrroles, as well as furan, thiophene and carbocyclic aromatics, further demonstrates the advantages of these reactions. We show that the reactivity of the sulfondiimidoyl fluorides can be tuned by switching the N-substituents, allowing an expansion of the range of coupling partners. The utility of the transformation is exemplified by the synthesis of the sulfondiimine analogue of the HIV-I reverse transcriptase-inhibitor L-737,126.

Modular Two-Step Route to Sulfondiimidamides.

Sulfur functional groups are common motifs in bioactive molecules. Sulfonamides are most prevalent but related aza-derivatives, in which oxygen atoms are replaced by imidic nitrogens, such as sulfoximines and sulfonimidamides, are gaining attraction. Despite this activity, the double aza-variants of sulfonamides, termed sulfondiimidamides, are almost completely absent from the literature. The reason for this is poor synthetic accessibility. Although a recent synthesis has established sulfondiimidamides as viable motifs, the length of the route and the capricious nature of the key sulfondiimidoyl fluoride intermediates mean that direct application to discovery chemistry is challenging. Herein, we describe a two-step synthesis of sulfondiimidamides, exploiting a hypervalent iodine-mediated amination as the key step. The starting materials are organometallic reagents, an unsymmetrical sulfurdiimide, and amines. The method allowed >40 examples to be prepared, including derivatives of three sulfonamide-based drugs. The operational simplicity, broad scope, and concise nature make this route attractive for discovery chemistry applications.

Congenital absence of left atrial appendage combined with type A Wolff-Parkinson-White syndrome diagnosed by multimodal imaging.

The absence of left atrial appendage (LAA) is relatively rare, especially with type A Wolff-Parkinson-White syndrome. Secondly, we diagnosed it by multimodal imaging including two-dimensional (2D) and three-dimensional (3D) transesophageal echocardiography (TEE), CT, electrophysiological examination, and 3D electro anatomical mapping system, which is more comprehensive.

Echocardiographic Measurements in Normal Chinese Adults (EMINCA) II focusing on left ventricular and left atrial size and function by three-dimensional echocardiography.

Current guidelines encourage large studies in a diverse population to establish normal reference ranges for three-dimensional (3D) echocardiography for different ethnic groups. This study was designed to establish the normal values of 3D-left ventricular (LV) and left atrial (LA) volume and function in a nationwide, population-based cohort of healthy Han Chinese adults. A total of 1117 healthy volunteers aged 18-89 years were enrolled from 28 collaborating laboratories in China. Two sets of 3D echocardiographic instruments were used, and full-volume echocardiographic images were recorded and transmitted to a core laboratory for image analysis with a vendor-independent off-line workstation. Finally, 866 volunteers (mean age of 48.4 years, 402 men) were qualified for final analysis. Most parameters exhibited substantial differences between different sex and age groups, even after indexation by body surface area. The normal ranges of 3D-LV and 3D-LA volume and function differed from those recommended by the American Society of Echocardiography and the European Association of Cardiovascular Imaging guidelines, presented by the World Alliance Societies of Echocardiography (WASE) study, and from the 2D values in the EMINCA study. The normal reference values of 3D echocardiography-derived LV and LA volume and function were established for the first time in healthy Han Chinese adults. Normal ranges of 3D-LV and 3D-LA echocardiographic measurements stratified with sex, age, and race should be recommended for clinical applications.

Right ventricular volume and function by three-dimensional echocardiography: results of the echocardiographic measurements in normal Chinese adults (EMINCA) II.

Three-dimensional (3D) echocardiography is an emerging technique for assessing right ventricular (RV) volume and function, but 3D-RV normal values from a large Chinese population are still lacking. The aim of the present study was to establish normal values of 3D-RV volume and function in healthy Chinese volunteers. A total of 1117 Han Chinese volunteers from 28 laboratories in 20 provinces of China were enrolled, and 3D-RV images of 747 volunteers with optimal image quality were ultimately analyzed by a core laboratory. Both vendor-dependent and vendor-independent software platforms were used to analyze the 3D-RV images. We found that men had larger RV volumes than women did in the whole population, even after indexing to body surface area, and older individuals had smaller RV volumes. The normal RV volume was significantly smaller than that recommended by the American Society of Echocardiography/European Association of Cardiovascular Imaging guidelines in both sexes. There were significant differences in 3D-RV measurements between the two vendor ultrasound systems and the different software platforms. The echocardiographic measurements in normal Chinese adults II study revealed normal 3D-RV volume and function in a large Chinese population, and there were significant differences between the sexes, ages, races, and vendor groups. Thus, normal 3D-RV values should be stratified by sex, age, race, and vendor.

Left ventricular global longitudinal strain using a novel fully automated method: A head-to-head comparison with a manual layer-specific strain and establishment of normal reference ranges.

BACKGROUND: A novel automated method for measuring left ventricular (LV) global longitudinal strain (GLS) along the endocardium has advantages in terms of its rapid application and excellent reproducibility. However, it remains unclear whether the available normal range for conventional GLS using the manual method is applicable to the automated GLS method. This study aimed to compare automated GLS head-to-head with manual layer-specific GLS, and to identify whether a specialized normal reference range for automated GLS is needed and explore the main determinants. METHODS: In total, 1683 healthy volunteers (men, 43%; age, 18-80 years) were prospectively enrolled from 55 collaborating laboratories. LV GLS was measured using both manual layer-specific and automated methods. RESULTS: Automated GLS was higher than endocardial, mid-myocardial, and epicardial GLS. Women had a higher automated GLS than men. GLS had no significant age dependency in men, but first increased and then decreased with age in women. Accordingly, sex- and age-specific normal ranges for automated GLS were proposed. Moreover, GLS appeared to have different burdens in relation to dominant determinants between the sexes. GLS in men showed no dominant determinants; however, GLS in women correlated with age, body mass index, and heart rate. CONCLUSIONS: Using the novel automated method, was LV GLS higher than when using the manual GLS method. The normal ranges of automated GLS stratified according to sex and age were provided, with dominant determinants showing sex disparities that require full consideration in clinical practice.

The characteristic of the complete chloroplast genome of Lithocarpus konishii (Fagaceae), a rare and endemic species in South China.

Lithocarpus konishii, a rare species endemic to islands in South China, was evaluated as a vulnerable species (VU) by the 'China Species Red List.' Here, we first presented the complete chloroplast genome sequence of L. konishii. The chloroplast genome was 161,059 bp in length with 36.76% GC content, containing a small single-copy region (SSC, 18,967 bp), a large single-copy region (LSC, 90,250 bp), and a pair of inverted repeats (IRs, 25,921 bp each). A total of 139 genes were predicted, including 87 protein-coding genes (CDS), 8 rRNAs, and 44 tRNAs. Based on the concatenated shared unique CDS sequence dataset, maximum-likelihood and Bayesian inference methods were used to build the phylogenetic trees of 18 species from the Fagaceae family. Results indicated that L. konishii is closely related to L. longnux and L. pachyphyllus var. fruticosus, and forms a monophyly of the subfamily Castaneoideae with Castanopsis and Castanea. This study provides a theoretical basis for the conservation genomics of this endangered plant.

Comprehensive Evaluation of Cancer Treatment-Related Cardiac Dysfunction by Ultrasound Myocardial Strain: A Network Meta-Analysis.

Anticancer treatment regimens are effective but may lead to cardiac dysfunction. The meaning of this statement is that myocardial strain can be a good indicator of cancer treatment-related cardiac dysfunction. We used Bayesian network meta-analysis to compare and rank these regimens to comprehensively evaluate their influence on the heart. We searched multiple databases to identify relevant studies. Global longitudinal strain (GLS), global radial strain, global circumferential strain, and other parameters were collected at baseline (T0), from baseline to 3 months of follow-up (T3), from 3 months to 6 months of follow-up (T6), and from 6 months to 12 months or longer of follow-up (T12). The weight mean differences (WMD) with 95% confidence intervals (CI) were used to express continuous variables. Direct and indirect comparison and ranking of different regimens based on the forest plots and the surface under the cumulative ranking area. A total of 4613 subjects were included in 33 studies. Anthracycline-based chemotherapy (ANT), trastuzumab, paclitaxel plus carboplatin or clofarabine, and radiotherapy (RT) were more likely to reduce GLS and global circumferential strain at T3 and T12. In particular, ANT+RT resulted in a more significant decrease in GLS than ANT alone at T12 (WMD 1.15; 95% CI, 0.05-2.26). Interestingly, cardioprotective treatment regimens, such as anthracycline plus bisoprolol plus angiotensin-converting enzyme inhibitors (ANT+BB+ACEIs) (WMD -2.79; 95% CI, -5.06 to -0.52), and ANT plus rosuvastatin (STATINs) (WMD -2.92; 95% CI, -5.54 to -0.29), were more likely to improve GLS than ANT at T12. The included anticancer regimens, especially ANT+RT, reduced GLS at T12, but their combination with cardioprotective drugs improved them. These results will help clinicians choose the best therapy regimens.

Novel exosome-related risk signature as prognostic biomarkers in glioblastoma.

Exosomes are progressively being detected as an indicator for the diagnosis and prognosis of cancer in clinical settings. Many clinical trials have confirmed the impact of exosomes on tumor growth, particularly in anti-tumor immunity and immunosuppression of exosomes. Therefore, we developed a risk score based on genes found in glioblastoma-derived exosomes. In this study, we used the TCGA dataset as the training queue and GSE13041, GSE43378, GSE4412, and CGGA datasets as the external validation queue. Based on machine algorithms and bioinformatics methods, an exosome-generalized risk score was established. We found that the risk score could independently predict the prognosis of patients with glioma, and there were significant differences in the outcomes of patients in the high- and low-risk groups. Univariate and multivariate analyses showed that risk score is a valid predictive biomarker for gliomas. Two immunotherapy datasets, IMvigor210 and GSE78220, were obtained from previous studies. A high-risk score showed a significant association with multiple immunomodulators that could act on cancer immune evasion. The exosome-related risk score could predict the effectiveness of anti-PD-1 immunotherapy. Moreover, we compared the sensitivity of patients with high- and low-risk scores to various anti-cancer drugs and found that patients with high-risk scores had better responses to a variety of anti-cancer drugs. The risk-scoring model established in this study provides a useful tool to predict the total survival time of patients with glioma and guide immunotherapy.

Incremental value of non-invasive myocardial work for the evaluation and prediction of coronary microvascular dysfunction in angina with no obstructive coronary artery disease.

Background: Evidence suggests that patients suffering from angina with no obstructive coronary artery disease (ANOCA) experience coronary microvascular dysfunction (CMD). We aimed to understand the diagnosis value of noninvasive myocardial work indices (MWIs) with left ventricular pressure-strain loop (LV PSL) by echocardiography in ANOCA patients with CMD. Methods: 97 patients with ANOCA were recruited. All subjects underwent standard echocardiography with traditional ultrasound parameters, two-dimensional speckle-tracking echocardiography with global longitudinal strain (GLS), LV PSL with MWIs include global work index (GWI), global constructive work (GCW), global waste work (GWW) and global work efficiency (GWE). In addition, all enrolled cases underwent high-dose adenosine stress echocardiography (SE) with coronary flow velocity reserve (CFVR). CMD was defined as CFVR <2.0. Results: Of the 97 patients with ANOCA, 52 were placed in the CMD group and 45 in the control group. GWI and GCW were decreased significantly in the CMD group compared with the control group (P < 0.001 for both). GWI and GCW were moderately correlated with CFVR (r = 0.430, P < 0.001 and r = 0.538, P < 0.001, respectively). In the multiple logistic regression analyses, GCW was identified as the only independent echocardiography parameter associated with CMD after adjusting for age and baseline APV [OR (95%CI) 1.009 (1.005-1.013); P < 0.001]. Moreover, the best predictor of CMD in patients with ANOCA using receiver operating characteristic (ROC) curve was GWI and GCW, with an area under the curve (AUC) of 0.800 and 0.832, sensitivity of 67.3% and 78.8%, specificity of 80.0% and 75.6%, respectively. Conclusion: MWIs with LV PSL is a new method to detect LV systolic function noninvasively in ANOCA patients with CMD.

Commelinadanxiaensis (Commelinaceae), a new species from Guangdong, China.

Commelinadanxiaensis (Commelinaceae), a remarkable new species from Mount Danxia, Guangdong Province, China, is described and illustrated. This species is similar to C.communis in inflorescences and flowers but readily distinguishable in its nearly erect stems, larger flowers, and different petal colouration.

Normal reference values for mitral annular plane systolic excursion by motion-mode and speckle tracking echocardiography: a prospective, multicentre, population-based study.

AIMS: Mitral annular plane systolic excursion (MAPSE) is a simple and reliable index for evaluating left ventricular (LV) systolic function, particularly in patients with poor image quality; however, the lack of reference values limits its widespread use. This study aimed to establish the normal ranges for MAPSE measured using motion-mode (M-mode) and two-dimensional speckle tracking echocardiography (2D-STE) and to explore its principal determinants. METHODS AND RESULTS: This multicentre, prospective, cross-sectional study included 1952 healthy participants [840 men (43%); age range, 18-80 years] from 55 centres. MAPSE was measured using M-mode echocardiography and 2D-STE. The results showed that women had a higher MAPSE than men and MAPSE decreased with age. The age- and sex-specific reference values for MAPSE were established for these two methods. Multiple linear regression analyses revealed that MAPSE on M-mode echocardiography correlated with age and MAPSE on 2D-STE with age, blood pressure (BP), heart rate, and LV volume. Moreover, MAPSE measured by 2D-STE correlated more strongly with global longitudinal strain compared with that measured using M-mode echocardiography. CONCLUSION: Normal MAPSE reference values were established based on age and sex. BP, heart rate, and LV volume are potential factors that influence MAPSE and should be considered in clinical practice. Normal values are useful for evaluating LV longitudinal systolic function, especially in patients with poor image quality, and may further facilitate the use of MAPSE in routine assessments.

Hearty recipes for health: the Hakka medicinal soup in Guangdong, China.

BACKGROUND: The Hakka are a subgroup of the Han Chinese, originally from northern China and mainly living in southern China now. Over hundreds of years, the Hakka have developed their own medical practices to prevent and cure diseases, such as medicinal soup, an important characteristic of Hakka cuisine. This study aims at documenting plant taxa used to make Hakka medicinal soup, along with their associated ethnomedical knowledge. METHODS: Data on Hakka soup-making plants were collected through key-informant interviews, semi-structured interviews, participatory field collection, and direct observation. The choosing of participants has followed the snowball sampling method. Herbs used for preparing medicinal soup were purchased on the local market or collected from the wild, and voucher specimens were collected and identified. The study result was also compared with published studies on soup-making plants in other parts of Guangdong province and the Hakka areas in Fujian Province of China. RESULTS: Eighty-three taxa belonging to 70 genera within 38 families were listed by our informants as being used to treat 55 kinds of health problems. Most documented plants are herbaceous species, followed by shrubs and woody liana. Roots were the most frequently used plant parts for medicinal purposes, followed, in descending order, by the whole plant, rhizomes, and flowers. Most plants used to prepare medicinal soup are wild-harvested (56 species), 4 cultivated, and 23 wild harvested or cultivated. According to the comparison, 18 Hakka medicinal soup species are shown both in Fujian Province and Guangdong Province. The Hakka soup-making plants in both provinces share very similar therapeutic functions. This study helps to extend the Hakka menu in both provinces. The study comparison also showed a big difference in the herb ingredients between Guangdong Hakka medicinal soup and Cantonese slow-cooked soup. CONCLUSION: Hakka medicinal soup is an important feature of the Hakka dietary culture. More studies are needed to be undertaken, especially on the efficacy and safety of this medicinal soup. Moreover, cultivation and conservation efforts are required to ensure the sustainability of the species that are used as ingredients in the soup. Consequently, further commercial development of medicinal soup should be promoted.

Comprehensive Meta-Analysis of Functional and Structural Markers of Subclinical Atherosclerosis in Women with Polycystic Ovary Syndrome.

The relationship between polycystic ovary syndrome (PCOS) and subclinical atherosclerosis remains unclear. We performed a comprehensive systematic review and meta-analysis to evaluate the effect of PCOS on functional and structural markers of subclinical atherosclerosis as measured by carotid intima-media thickness (cIMT), flow-mediated vasodilation (FMD), nitroglycerin-mediated vasodilation (NMD), pulse wave velocity (PWV), and coronary artery calcium (CAC). Standard mean differences (SMDs) or odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were calculated. Ninety-six articles involving 5550 PCOS patients and 5974 controls were included. Compared with controls, PCOS patients showed significantly thicker cIMT (SMD (95% CI) = .587 (.398, .776), P < .001), lower FMD (SMD (95% CI) = -.649 (-.946, -.353), P < .001) and NMD (SMD (95% CI) = -.502 (-.686, -.317), P < .001), as well as higher PWV (SMD (95% CI) = .382 (.019, .746), P = .039), and increased CAC incidence (OR (95% CI) = 2.204 (1.687, 2.879), P < .001). When analyzing subgroups by age and body mass index (BMI), results were still significant (P < .05) except for PWV in the BMI subgroup. There was no significant result on sensitivity analysis, and Begg' test or Egger's test. PCOS contributes to subclinical atherosclerosis, resulting in functional and structural changes in cIMT, FMD and NMD, PWV, and CAC incidence.

A Silyl Sulfinylamine Reagent Enables the Modular Synthesis of Sulfonimidamides via Primary Sulfinamides.

A new N-silyl sulfinylamine reagent allows the rapid preparation of a broad range of (hetero)aryl, alkenyl, and alkyl primary sulfinamides, using Grignard, organolithium, or organozinc reagents to introduce the carbon fragment. Treatment of these primary sulfinamides with an amine in the presence of a hypervalent iodine reagent leads directly to NH-sulfonimidamides. This two-step sequence is straightforward to perform and provides a modular approach to sulfonimidamides, allowing ready variation of both reaction components, including primary and secondary amines.

Multimodal Imaging for Total Anomalous Systemic Venous Drainage Diagnosis and Preoperative Planning: A Case Report and Literature Review.

Total anomalous systemic venous drainage (TASVD) is a rare congenital heart malformation. Here, we report a case of a 40-year-old male patient who had a total anomalous systemic venous drainage. It was diagnosed as the TASVD for the first time through multimodal imaging combined Transthoracic (TTE), transesophageal (TEE) and three-dimensional (3D-TTE) echocardiography, contrast echocardiography and computed tomography angiography (CTA). We review 15 published reports on TASVD and summarize the ultrasonographic characteristics. After intracardiac repair through ectopic venous drainage in cardiac surgery, the patient's cyanosis symptoms were alleviated greatly. Echocardiography was the first-line examination for TASVD. Multimodal imaging combined TTE, TEE, 3D TEE, contrast echocardiography and CTA was necessary for confirmed diagnosis of TASVCD.

Diffuse Primary Malignant Pericardial Mesothelioma With Myocardial involvement: A Comprehensive Assessment Using Multimodel Echocardiography.

Diffuse primary malignant pericardial mesothelioma (PMPM) is an extremely rare and highly invasive tumor of pericardium. The tumor can infiltrate myocardium in part of cases, and will contribute to grave prognosis. Herein, we reported a 58-year-old man of diffuse PMPM with myocardial involvement, and summarized 39 cases of diffuse PMPM. Multimodal echocardiography, which combined conventional, tissue Doppler and speckle tracking echocardiography, was applied to diagnose diffuse PMPM with myocardial involvement, and assess the myocardial function. The common features were pericardial effusion, pericardial masses and thickened pericardium. The other echocardiographic characteristics were extensive and heterogenous echo, adhesion with pericardium and myocardium, reduced motion of adhered myocardium, and constriction performance. Diffuse PMPM with myocardial involvement revealed decreased LV diastolic function, and decreased LV and RV systolic function. Especially in systolic function, the unique strain features were reduced longitudinal strains from segmental to global and from epicardial to endocardial, relative 'septal sparing' pattern, and decreased transmural gradient of longitudinal strain. Our findings suggested that multimodal echocardiography not only can identify this disease, but also can provide detailed information of myocardial dysfunction, which provides a reference for clinicians to develop an optimal individualized treatment.

The association between heart rate reserve and impaired coronary flow velocity reserve: a study based on adenosine stress echocardiography.

This study was to explore the correlation between heart rate reserve (HRR) to coronary flow velocity reserve (CFVR), using adenosine stress echocardiography (SE), in patients with angina and no obstructive coronary artery disease (ANOCA). 111 ANOCA patients underwent adenosine SE were enrolled, which were divided into two groups, impaired CFVR group (CFVR < 2) and control groups (CFVR ≥ 2). The relationships between HRR and impaired CFVR were explored in total and subgroup to sex. A reduced HRR during adenosine infusion was seen in ANOCA patients with impaired CFVR (25.73 ± 8.39 vs. 34.30 ± 19.93, P < 0.001). Compared to respective controls, the blunted HRR to adenosine was more pronounced in female patients (women: 27.21 ± 8.01 vs. 39.48 ± 10.57, P < 0.001; men: 24.05 ± 8.70 vs. 29.12 ± 8.69, P = 0.041). A strong association between CFVR and a blunted HRR was observed in women (r = 0.46, P < 0.001), while no association in men (r = 0.18, P = 0.199). In female, a multivariate logistic regression identified HRR as the strongest negative predictor of impaired CFVR [HR (95% CI) = 0.854 (0.764-0.956), P = 0.006]. Based on the ROC curve, HRR < 35% was a strong indicator of impaired CFVR, with AUC of 0.838, sensitivity of 70%, and specificity of 87% in females. A blunted HRR was seen in patients with impaired CFVR, with a most pronounced effect being seen in female patients. The blunted HRR < 35% is intricately linked to impaired CFVR in women with ANOCA beyond the value of traditional risk factors, which could ultimately contribute to risk stratification of impaired CFVR in such patients.

The efficacy and safety of multiple versus single doses dexamethasone in unicompartmental knee arthroplasty: A protocol of randomized controlled trial.

BACKGROUND: Concerns exist regarding the analgesia effect and safety of multiple versus single doses dexamethasone in unicompartmental knee arthroplasty. There is an urgent need of studies that efficiently control for confounding, conduct comprehensive and consecutive observation of potential risks of the dexamethasone administration, and investigate its clinical applicability. We thus further designed a randomized controlled study to assess the different dose of dexamethasone on postoperative pain and complications in patients undergoing unicompartmental knee arthroplasty. METHODS: This randomized, prospective, controlled study was carried out between January 2018 and August 2019. It was approved by the institutional review board in our hospital (HBRM2020013). A total of 80 patients were randomly assigned to each group: the study group (n = 40) and the control group (n = 40). All surgical procedures were performed by a similar orthopedic surgeon. In the study group, patients received intravenously 20 mg dexamethasone (4 mL, Tianjin Kingyork group Co., Ltd., China) just after the anesthesia, and repeated at 24 hours after the surgery. Patients in the control group received intravenously 10 mg dexamethasone solution (2 mL) just after the anesthesia, and repeated at 24 hours after the surgery. CRP, IL-6, VAS pain scores at rest and walking, the VAS scores of nausea, and the incidence of postoperative vomiting and nausea (POVN) were recorded at 24, 48, and 72 hours postoperatively. CONCLUSION: We hypothesized that patients receiving multiple doses of dexamethasone was associated with better outcomes compared with patients receiving single dose of dexamethasone. TRIAL REGISTRATION: This study protocol was registered in Research Registry (researchregistry5770).