bluuebunny/crossref_metadata_2025_split huggingface dataset:
Five Percent Monolaurin Vaginal Gel for the Treatment of Bacterial Vaginosis: A Randomized Placebo-Controlled Trial
Authors: Mancuso Abigail C. , Widdice Lea E. , Hughes Brenna L. , Schlievert Patrick , Swamy Geeta K. , Stockdale Colleen K. , Bernstein David I. , Winokur Patricia L. 
Published: May 2020

Objective
The aim of the study was to test the hypothesis that 5% monolaurin vaginal gel, a naturally occurring monoglyceride shown to have antimicrobial effects on vaginal pathogens without affecting Lactobacillus species, cures bacterial vaginosis (BV).

Materials and Methods
This was a multicenter, double-blinded, randomized controlled trial comparing 5% monolaurin vaginal gel to vehicle placebo (glycol-based) gel administered twice daily for 3 days. Nonpregnant, nonbreastfeeding women between ages 18 and 50 years were recruited and BV confirmed. Primary outcome was clinical cure assessed by resolution of all 4 Amsel criteria. Secondary outcomes included safety and tolerability assessed by solicited urogenital adverse events. Exploratory outcomes included colony counts for vaginal microbes associated with healthy vaginal flora (Lactobacillus species) and the dysbiosis often associated with BV (Gardnerella species and Mobiluncus species). A 2:1 test article to placebo randomization scheme was planned.

Results
One hundred nine women participated with 73 randomized to the treatment arm and 36 to the placebo arm. There was no significant difference in clinical cure for BV (p = .42) with 17% of the monolaurin group and 25% of the placebo group achieving clinical cure. Lactobacilli species counts increased in the monolaurin group compared with placebo (1.0 × 107 vs −5.2 × 106). Two thirds of both groups reported solicited urogenital adverse events, but these were mild to moderate with no significant difference between groups (p = .24).

Conclusions
Monolaurin was no more clinically or microbiologically effective than placebo in curing BV. Future research should explore whether monolaurin may be used to increase Lactobacilli species.
Short-term prognosis of unstable angina in the era of high-sensitivity cardiac troponin: insights for early rule-out strategies
Authors: Gallone Guglielmo , Magnoni Marco , Vergani Vittoria , Ceriotti Ferruccio , Angeloni Giulia , Scarano Paola , Maseri Attilio , Cianflone Domenico 
Published: May 2020

Background
It is unclear if strategies to rule-out myocardial infarction (MI) based on a single high-sensitivity troponin T (hsTnT) measurement at the emergency department (ED) presentation may also exclude unstable angina.

Methods
We measured hsTnT ex-post on the admission frozen blood sample of 644 subjects with Braunwald IIIB CK-MB-negative unstable angina. This analysis included the 240 patients with hsTnT value ≤99th percentile reference limit (UA). We evaluated the clinical outcome of UA patients and the applicability of two rule-out strategies based on the combination of a non-ischemic ECG with (1) a single hsTnT value below the Limit-of-Detection (LoD), (2) a TIMI risk score ≤1.

Results
UA patients with hsTnT ≤99th percentile reference limit had a favorable 30-day outcome [0.8% MI, 0% cardiovascular death (CVD)], but the rate of CVD/MI at 180-day was 4.7%. Sensitivities for UA were 94.6% according to the ‘TIMI ≤1-strategy’ and 75.4% according to ‘hsTnT-below-LoD-strategy’, accounting for 5.4 and 24.6% missed diagnoses, respectively. A prognostic risk stratification to guide appropriate outpatient assessment in potential discharged unrecognized UA patients was developed: a risk score based on the combination of age >60 years and C-reactive protein >4.5 mg/L effectively stratified the 180-day CVD/MI occurrence: 0, 2.5 and 12.7% for score 0, 1 and 2 (log-rank = 0.001, C-statistic = 0.776).

Conclusion
Single measurement hsTnT strategies, successfully tested to rule-out MI, may allow safe ED discharge of patients with a suspected acute coronary syndrome: even if UA may not be excluded, its short-term prognosis is favorable. UA patients with a C-reactive protein >4.5 mg/L and older than 60 years have a substantial medium-term cardiovascular risk and may benefit from a timely outpatient diagnostic assessment.
A Network Meta-Analysis of Randomized Controlled Trials on the Treatment of Eosinophilic Esophagitis in Adults and Children
Authors: Rokkas Theodore , Niv Yaron , Malfertheiner Peter 
Published: May 2020

Background:
Network meta-analysis is used as a data synthesizer, incorporating direct and indirect evidence about treatments in a series of randomized control trials.

Objective:
To evaluate the comparative efficacy of various treatments for eosinophilic esophagitis (EoE).

Methods:
We performed a network meta-analysis to combine direct and indirect data to investigate the efficiency of drug therapies, which were evaluated in relevant randomized control trials for EoE.

Results:
Seventeen eligible studies (14 two-arm and 3 multiple-arm) were introduced to the meta-analysis. A total of 1011 patients were included, in whom 15 therapeutic interventions were used, namely: (1) budesonide oral suspension, (2) budesonide 1 mg orodispersible tablet twice daily, (3) budesonide 2 mg orodispersible tablet twice daily, (4) esomeprazole, (5) fluticasone, (6) nebulized steroid, (7) placebo, (8) prednisone, (9) anti-IL-5-mab (mepolizumab), (10) anti-IL-5-mab [reslizumab(1), ie, 1 mg/kg], (11) anti-IL-5-mab [reslizumab(2), ie, 2 mg/kg], (12) anti-IL-5-mab [reslizumab(3), ie, 3 mg/kg], (13) anti-IL-13-mab (QAX 576), (14) anti-IL-13-mab [RCP 4046 (180)], and (15) anti-IL-13-mab [RCP 4046 (360)]. Budesonide 1 mg orodispersible tablet twice daily showed the highest efficacy (SUCRA 0.91), whereas placebo was the least effective. In adult patients budesonide 1 mg orodispersible tablet twice daily remained the optimal treatment approach, whereas the corresponding therapeutic approach in pediatric patients was fluticasone.

Conclusions:
This meta-analysis showed that budesonide 1 mg orodispersible tablet twice daily was the best treatment for EoE, as it was the most effective. This treatment remained the optimal approach in adult patients, whereas fluticasone was the best treatment in pediatric patients.
Low Risk of Progression of Barrett’s Esophagus to Neoplasia in Women
Authors: Allen James E. , Desai Madhav , Roumans Carlijn A.M. , Vennalaganti Sreekar , Vennalaganti Prashanth , Bansal Ajay , Falk Gary , Lieberman David , Sampliner Richard , Thota Prashanthi , Vargo John , Gupta Neil , Moawad Fouad , Bruno Marco , Kennedy Kevin F. , Gaddam Srinivas , Young Patrick , Mathur Sharad , Cash Brooks , Spaander Manon , Sharma Prateek 
Published: May 2020

Background and Aims:
Men are at a higher risk for Barrett’s esophagus (BE) and esophageal adenocarcinoma (EAC), but little is known about BE progression to dysplasia and EAC in women. We performed a retrospective, multicenter cohort study to assess risk of BE progression to dysplasia and EAC in women compared with men. We also investigated comorbidities, medication use, and endoscopic features that contribute to sex differences in risk of BE progression.

Methods:
We collected data from large cohort of patients with BE seen at 6 centers in the United States and Europe, followed for a median 5.7 years. We obtained demographic information (age, sex, ethnicity), clinical history (tobacco use, body mass index, comorbidities), endoscopy results (procedure date, BE segment length), and histopathology findings. Neoplasia was graded as low-grade dysplasia, high-grade dysplasia (HGD), or EAC. Rates of disease progression between women and men were compared using χ2 analysis and the Student t test. Multivariable logistic regression was used to assess the association between sex and disease progression after adjusting for possible confounding variables.

Results:
Of the total 4263 patients in the cohort, 2145 met the inclusion criteria, including 324 (15%) women. There was a total of 34 (1.6%) incident EACs, with an overall annual incidence of 0.3% (95% confidence interval: 0.2%-0.4%). We found significant differences between women and men in annual incidence rates of EAC (0.05% for women vs. 0.3% in men; P=0.04) and in the combined endpoint of HGD or EAC (0.1% for women vs. 1.1% for men; P<0.001). Female gender was an independent predictor for reduced progression to HGD or EAC when rates of progression were adjusted for body mass index, smoking history, race, use of aspirin, nonsteroidal anti-inflammatory drugs, proton-pump inhibitors, or statins, hypertriglyceridemia, BE length, and histology findings at baseline (hazard ratio: 0.11; 95% confidence interval: 0.03-0.45; P=0.002).

Conclusions:
In a multicenter study of men versus women with BE, we found a significantly lower risk of disease progression to cancer and HGD in women. The extremely low risk of EAC in women with BE (0.05%/y) indicates that surveillance endoscopy may not be necessary for this subgroup of patients with BE.
A phase I/IIa double blind single institute trial of low dose sirolimus for Pendred syndrome/DFNB4
Authors: Fujioka Masato , Akiyama Takumi , Hosoya Makoto , Kikuchi Kayoko , Fujiki Yuto , Saito Yasuko , Yoshihama Keisuke , Ozawa Hiroyuki , Tsukada Keita , Nishio Shin-ya , Usami Shin-ichi , Matsunaga Tatsuo , Hasegawa Tomonobu , Sato Yasunori , Ogawa Kaoru 
Published: May 2020

Abstract

Introduction:
Pendred syndrome (PDS)/DFNB 4 is a disorder with fluctuating and progressive hearing loss, vertigo, and thyroid goiter. We identified pathophysiology of a neurodegenerative disorder in PDS patient derived cochlear cells that were induced via induced pluripotent stem cells and found sirolimus, an mTOR inhibitor, as an inhibitor of cell death with the minimum effective concentration less than 1/10 of the approved dose for other diseases. Given that there is no rational standard therapy for PDS, we planned a study to examine effects of low dose oral administration of sirolimus for the fluctuating and progressive hearing loss, and the balance disorder of PDS by daily monitor of their audio-vestibular symptoms.

Methods and analysis:
This is a phase I/IIa double blind parallel-group single institute trial in patient with PDS/DFNB4. Sixteen of outpatients with fluctuating hearing diagnosed as PDS in SLC26A4 genetic testing aged in between 7 and 50 years old at the time of consent are given either placebo or sirolimus tablet (NPC-12T). In NPC-12T placebo arm, placebo will be given for 36 weeks; in active substance arm, placebo will be given for 12 weeks and the NPC-12T for 24 weeks. Primary endpoints are safety and tolerability. The number of occurrences and types of adverse events and of side effects will be sorted by clinical symptoms and by abnormal change of clinical test results. A 2-sided 95% confidence interval of the incidence rate by respective dosing arms will be calculated using the Clopper–Pearson method. Clinical effects on audio-vestibular tests performed daily and precise physiological test at each visit will also be examined as secondary and expiratory endpoints.

Trial registration number:
JMA-IIA00361; Pre-results.
GERD outcome after bariatric surgery
Authors: Elzouki Abdel-Naser , Waheed Muhammad-Aamir , Suwileh Salah , Adoor Dayyan M. , Tashani Osama , Abou Samra Abdul-Badi 
Published: May 2020

Abstract

Background/Aim:
Obesity is associated with increased incidence of gastroesophageal reflux disease (GERD), and it has been suggested that GERD symptoms may be improved by weight reduction. However, various patterns of bariatric surgery may affect symptoms of GERD due to the changed anatomy of stomach and esophagus. The aim of this systematic review and meta-analysis is to analyze the effect of bariatric surgery on GERD.

Materials and methods:
A systematic literature search was performed using PubMed, EMBASE, and the Cochrane Library from January 2005 to January 2019, combining the words obesity, gastroesophageal reflux with different types of bariatric surgery and weight loss. The methodological quality of randomized controlled trials and non-randomized controlled trials published in English and have at least 1-year follow-up data were included and assessed by Cochrane Collaboration's tool for assessing risk bias and Newcastle–Ottawa scale. Only clinical trials were included, and case series or case reports were excluded.

Results:
We anticipate that our review will provide the exact estimates of the burden and phenotype of GERD among patients that have undergone bariatric surgery.

Conclusion:
GERD may improve in obese patients who underwent laparoscopic sleeve gastrectomy (LSG); however, the most favorable effect is likely to be found after Roux-en-Y gastric bypass surgery.

Prospero registration number:
CRD42018090074.
Functional outcomes after treatments for different types of isolated ulnar coronoid fracture
Authors: Chen Hongwei , Wu Jinqing , Zhao Pinyi , Wu Lijun , Guo Chao 
Published: May 2020

Abstract

Background:
Optimal treatments for ulnar coronoid fracture have yet to be determined. We aimed to systematically review treatment efficacy assessed by functional outcomes of patients with isolated ulnar coronoid fracture.

Methods:
Medline, Cochrane Library, EMBASE, and Google Scholar were searched for studies reporting quantitative outcomes data after surgical treatment for isolated ulnar coronoid fractures up to July 16, 2019. Functional outcomes determined using disabilities of the arm, shoulder and hand score; Mayo elbow performance score (MEPS); and range of motion were systematically reviewed.

Results:
Six studies with a total of 65 patients with isolated coronoid fracture who had received surgical treatment were included. All studies were of good quality according to a modified Delphi checklist. Most patients had Type II fractures based on Regan-Morrey or O’Driscoll classification. Disabilities of the arm, shoulder and hand scores were reported by 2 studies (mean range 5–17). Four studies reported MEPS (mean range 89–98). One study reported Broberg-Morrey scores, in which 93% patients achieved excellent or good outcomes. Five studies reported range of motion, with mean flexion ranging from 122 to 137 and mean extension ranging from 4.0 to 21 degrees. Quantitative analyses revealed that lateral, medial, or posterior approaches in treating Type II fractures are associated with higher postoperative MEPS and flexion scores than the anteromedial approach.

Conclusions:
Treatment efficacy assessed by functional outcomes for isolated ulnar coronoid fractures is overall satisfactory. Whether lateral, medial, or posterior approaches lead to more favorable outcomes than the anteromedial approach is inconclusive. Further prospective studies are warranted.
Efficacy and safety of over-the-counter analgesics for primary dysmenorrhea
Authors: Nie Wenbo , Xu Ping , Hao Chunyan , Chen Yingying , Yin Yanling , Wang Lisheng 
Published: May 2020

Abstract

Background:
Primary dysmenorrhea is common and troublesome. The comparative efficacy of over-the-counter analgesics (OTCAs) for dysmenorrhea is unclear. This study was aimed at conducting a network meta-analysis to assess the efficacy and safety of 5 OTCAs – naproxen, ibuprofen,diclofenac, aspirin, and ketoprofen – in patients with primary dysmenorrhea.

Methods:
The study was registered with PROSPERO (number: CRD42019133556). The search strategy involved a review of PubMed, Embase, Cochrane Library, Web of Science, and CINAHL for relative randomized controlled trials of the 5 analgesics from the date of database establishment to July 2019. The outputs are presented as odds ratios (ORs), their corresponding 95% confidence intervals (CIs), and the surface under the cumulative ranking area (SUCRA) probabilities.

Results:
Thirty-five trials with 4383 participants were included in our study. As for efficacy outcomes, all the included analgesics except aspirin were more effective than placebo in treating dysmenorrhea [naproxen (OR 3.99, 95% CI 2.18–7.30), ibuprofen (OR 10.08, 95% CI 3.29–30.85), diclofenac (OR 11.82, 95% CI 2.66–52.48), and ketoprofen (OR 5.12, 95% CI 1.57–16.69). The OTCAs were superior to the placebo in terms of pain relief in primary dysmenorrhea. Aspirin was less effective than ibuprofen (OR 0.17, 95% CI 0.04–0.73) and diclofenac (OR 1.17, 95% CI 0.02–0.85). The SUCRA curves showed that diclofenac and ibuprofen were the most and second most effective (85.1% and 83.8%, respectively), followed by ketoprofen, naproxen, and aspirin. Regarding safety, there was no significant difference between the 5 OTCAs included and the placebo. Diclofenac versus ibuprofen (OR 4.31, 95% CI 1.18–15.67), ketoprofen versus diclofenac (OR 0.18, 95% CI 0.04–0.78), and ketoprofen versus aspirin (OR 0.41, 95% CI 0.18–0.97) presented statistically significant differences. Ketoprofen and ibuprofen were ranked the best (SUCRA 90.6% and 79.6%), followed by naproxen, aspirin, and diclofenac.

Conclusion:
Considering the efficacy and safety, ibuprofen is recommended as the optimal OTCA for primary dysmenorrhea. Further well-designed studies that directly compare these analgesics are needed to support our conclusion.
Tryptophan pathway catabolites (serotonin, 5-hydroxyindolacetic acid, kynurenine) and enzymes (monoamine oxidase and indole amine 2,3 dioxygenase) in patients with septic shock
Authors: Troché Gilles , Henry-Lagarrigue Matthieu , Soppelsa Frédérique , Legriel Stephane , Yehia Aihem , Bruneel Fabrice , Bédos Jean-Pierre , Spreux-Varoquaux Odile 
Published: May 2020

Abstract
Septic shock is associated with a strong inflammatory response that induces vasodilation and vascular hyporeactivity. We investigated the role for tryptophan-pathway catabolites of proinflammatory cytokines in septic shock.
We prospectively included 30 patients with very recent-onset septic shock and 30 healthy volunteers. The following were assayed once in the controls and on days 1, 2, 3, 7, and 14 in each patient: plasma free and total tryptophan, platelet and plasma serotonin, total blood serotonin, urinary serotonin, plasma and urinary 5-hydroxyindolacetic acid, plasma kynurenine, monoamine oxidase activity, and total indole amine 2,3-dioxygenase activity. Organ-system failure and mortality were recorded.
Compared with the healthy controls, the patients with septic shock had 2-fold to 3-fold lower total tryptophan levels throughout the 14-day study period. Platelet serotonin was substantially lower, while monoamine oxidase activity and 5-hydroxyindolacetic acid were markedly higher in the patients than in the controls, consistent with the known conversion of tryptophan to serotonin, which is then promptly and largely degraded to 5-hydroxyindolacetic acid. Plasma kynurenine was moderately increased and indole amine 2,3-dioxygenase activity markedly increased in the patients versus the volunteers, reflecting conversion of tryptophan to kynurenine. Changes over time in tryptophan metabolites were not associated with survival in the patients but were associated with the Sequential Organ Failure Assessment score and hemodynamic variables including hypotension and norepinephrine requirements.
Our results demonstrate major tryptophan pathway alterations in septic shock. Marked alterations were found compared with healthy volunteers, and tryptophan metabolite levels were associated with organ failure and hemodynamic alterations. Tryptophan metabolite levels were not associated with surviving septic shock, although this result might be ascribable to the small sample size.
Trial registration: ClinicalTrials.gov; No: NCT00684736; URL: www.clinicaltrials.gov.
Application of Delphi method and analytic hierarchy process to establish indicator system for evaluation of rational drug use in children with primary nephrotic syndrome
Authors: Lin Mao , Zeng Linan , Huang Liang , Tao Yuhong , Zhang Lingli 
Published: May 2020

Abstract
Nephrotic syndrome (NS) can be divided into primary, secondary, and congenital NS 3 types, and primary nephrotic syndrome (PNS) accounts for about 90% of the total number of NS in children, which is a common childhood glomerular disease one. The treatment of children with PNS has been controversial and confused because of hormone tolerance, complications, multiple drug combinations, and other issues, but there are no indicators to assess the rational drug use (RDU) of children with PNS. This study aims to develop a set of indicators to assess the RDU in children with PNS.
The study is an observational study and the procedure includes 3 steps:
A consensus was reached after 2 rounds of the Delphi survey and each indicator was weighted. The final indicators included 2 first-rank indicators and 16 second-rank indicators. In round 1, modified 3 indicators, increase 2 indicators and delete 6 indicators. In round 2, reached consensus. The first-rank indicators comprised drug choice (46.96%) and drug usage and dosage (53.04%); The second-rank indicators aimed to the specific drug therapy, including the RDU of hormones, immunomodulators, and adjuvant drug. The score of each indicator met the requirements, therefore, childrens PNS RDU evaluation index system had been established and the index was scientific and credible.
The first set indicators had been established to assess RDU of children with PNS. Monitoring these indicators will guide people towards the promotion of RDU for PNS. Whats more, the indicator provided a methodological reference for the development of other indicator sets.
PDPN is a prognostic biomarker and correlated with immune infiltrating in gastric cancer
Authors: Hu Liya , Zhang Peng , Sun Wei , Zhou Lei , Chu Qian , Chen Yuan 
Published: May 2020

Abstract
Studies of PDPN in cancers have focused on the interactions with palates through the binding with CECL-2 which mainly express on palates and immune cells, while little is known on its interactions with immune cells.
PDPN expression in cancers was analyzed through Oncomine, GEPIA, and TIMER database. Prognostic value (HR, P value from log-rank test) was evaluated through Kaplan–Meier plotter and OncoLnc database. The correlations between PDPN and the infiltrating levels of immune cells in different cancers, and diverse immune markers in gastric cancer were investigated through TIMER database.
High PDPN expression predicted poor overall survival (OS) and post-progression survival (PPS) particularly in gastric cancer (OS P = .0089; PPS P = .00085), especially among patients with Her-2 (+) and lymph node metastasis. In addition, PDPN was positively correlated with infiltrating levels of immune cells, other than B cells in gastric cancer. However, PDPN showed more correlations with immune markers of M2 type TAM (CD163, VSIG4, MS4A4A) and T cell exhaustion (TIM-3, TOX, and GZMB).
These findings all suggest that high PDPN predicts poor survival outcomes, especially for Her-2 (+) gastric cancer patients. Though inducing M2 type TAM and T cell exhaustion, high PDPN can predict high levels of various immune cells infiltration in STAD. Those correlations may bring new ideas to immunology treatment for gastric cancer patients who do not benefit from the existing immune checkpoint inhibitors.