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1.
Gestational trophoblastic neoplasia (GTN) patients are treated according to the eight-variable International Federation of Gynaecology and Obstetrics (FIGO) scoring system, that aims to predict first-line single-agent chemotherapy resistance. FIGO is imperfect with one-third of low-risk patients developing disease resistance to first-line single-agent chemotherapy. We aimed to generate simplified models that improve upon FIGO. Logistic regression (LR) and multilayer perceptron (MLP) modelling (n = 4191) generated six models (M1-6). M1, all eight FIGO variables (scored data); M2, all eight FIGO variables (scored and raw data); M3, nonimaging variables (scored data); M4, nonimaging variables (scored and raw data); M5, imaging variables (scored data); and M6, pretreatment hCG (raw data) + imaging variables (scored data). Performance was compared to FIGO using true and false positive rates, positive and negative predictive values, diagnostic odds ratio, receiver operating characteristic (ROC) curves, Bland-Altman calibration plots, decision curve analysis and contingency tables. M1-6 were calibrated and outperformed FIGO on true positive rate and positive predictive value. Using LR and MLP, M1, M2 and M4 generated small improvements to the ROC curve and decision curve analysis. M3, M5 and M6 matched FIGO or performed less well. Compared to FIGO, most (excluding LR M4 and MLP M5) had significant discordance in patient classification (McNemar's test P < .05); 55-112 undertreated, 46-206 overtreated. Statistical modelling yielded only small gains over FIGO performance, arising through recategorisation of treatment-resistant patients, with a significant proportion of under/overtreatment as the available data have been used a priori to allocate primary chemotherapy. Streamlining FIGO should now be the focus.  相似文献   
2.
Pharmaceutical Chemistry Journal - Aseries 6-phenyl-2-(substituted methyl)-dihydropyridazinone derivatives (3a–3f) were synthesized using the interaction of 6-phenylpyridazinone with cyclic...  相似文献   
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Objectives: The aim of this study was to investigate the associations of asthma with the psychological profile (depression and anxiety) of children with asthma and their mothers as well as the attitudes of these mothers toward their children and their family relationships. Methods: Sixty-four children with asthma, 60 healthy children and their mothers were included in the study. The Children’s Depression Inventory (CDI) and Childhood Anxiety Sensitivity Index (CASI) were applied to the children. All mothers completed the Beck Depression Inventory, the State-Trait Anxiety Inventory, the Parental Attitude Research Instrument and the Family Assessment Device. Results: CASI scores were significantly higher in children with asthma (p?<?0.001) than in healthy children. The increasing duration and severity of asthma were associated with increasing anxiety levels in children with asthma. Depression and anxiety scores were significantly higher in the mothers of children with asthma than in the comparison group. The mothers of children with asthma did not have supportive and friendly relationships with their children. In addition, these mothers had significantly higher Attitude of Hostility and Rejection, Attitude of Over-parenting and Authoritarian Attitude scores than those of the comparison group. Increasing duration and severity of asthma influenced family functions and the attitude of the mothers of children with asthma. There was a correlation between an increasing number of emergency department visits and increasing depression in the mothers of children with asthma. Conclusions: This cross-sectional study revealed that the disease may negatively affect the lives of children with asthma and their mothers and their family relationships.  相似文献   
5.

Background

The Parkland Grading Scale for Cholecystitis (PGS) was developed as an intraoperative grading scale to stratify gallbladder (GB) disease severity during laparoscopic cholecystectomy (LC). We aimed to prospectively validate this scale as a measure of LC outcomes.

Methods

Eleven surgeons took pictures of and prospectively graded the initial view of 317?GBs using PGS while performing LC (LIVE) between 9/2016 and 3/2017. Three independent surgeon raters retrospectively graded these saved GB images (STORED). The Intraclass Correlation Coefficient (ICC) statistic assessed rater reliability. Fisher's Exact, Jonckheere-Terpstra, or ANOVA tested association between peri-operative data and gallbladder grade.

Results

ICC between LIVE and STORED PGS grades demonstrated excellent reliability (ICC?=?0.8210). Diagnosis of acute cholecystitis, difficulty of surgery, incidence of partial and open cholecystectomy rates, pre-op WBC, length of operation, and bile leak rates all significantly increased with increasing grade.

Conclusions

PGS is a highly reliable, simple, operative based scale that can accurately predict outcomes after LC.

Table of contents summary

The Parkland Grading Scale for Cholecystitis was found to be a reliable and accurate predictor of laparoscopic cholecystectomy outcomes. Diagnosis of acute cholecystitis, surgical difficulty, incidence of partial and open cholecystectomy rates, pre-op WBC, operation length, and bile leak rates all significantly increased with increasing grade.  相似文献   
6.
ABSTRACT

Background: Gene editing has shown huge potential in correcting aberrant splicing and Cas13 has been identified as being particularly suitable for targeting RNA. It has therefore become increasingly important to highlight new splice site mutations that may be correctable, particularly in genes that are too large to be encoded by AAV vectors. About 20% of Usher Type 1 cases are caused by mutations in CDH23.

Purpose: To report a novel splice site mutation of CDH23 associated with Usher Type 1D.

Materials and Methods: Case report.

Results: A 35-year-old Caucasian female who is congenitally deaf with vestibular dysfunction presented with visual acuity of 6/12 in both eyes. Fundus examination revealed findings typical of retinitis pigmentosa with foveal preservation of photoreceptor layer. Next generation sequencing analysis revealed a novel homozygous variant, c.9319 + 1G>T in CDH23 consistent with the diagnosis of Usher Syndrome Type 1D. The c.9319 + 1G>T variant is predicted to affect splicing at the exon 65/intron 65 boundary, which highly likely leads to complete skipping of exon 65.

Conclusions: We describe a case of a typical Usher Syndrome Type 1D caused by a novel splice site variant in CDH23. Currently there are no treatments for CDH23 related retinal degeneration, partly because the cDNA size of 10kb is too large for AAV vector gene augmentation therapy. Alternative strategies include CRISPR-Cas9 adenine base editors and RNA editing with CRISPR-Cas13. Single-nucleotide editing represents a promising approach for targeting this variant in CDH23 to restore the wildtype splice donor site at this position.  相似文献   
7.
IntroductionThere remains uncertainty regarding the differences in patient outcomes between monopolar transurethral resection of the prostate (MTURP) and bipolar TURP (BTURP) in the management of lower urinary tract symptoms (LUTS) secondary to benign prostatic obstruction (BPO).MethodsA systematic literature search was carried out up to March 19, 2019. Methods in the Cochrane Handbook were followed. Certainty of evidence (CoE) was assessed using the GRADE approach.ResultsA total of 59 randomized controlled trials (RCTs) with 8924 participants were included. BTURP probably results in little to no difference in International Prostate Symptom Score (IPSS) at 12 months (mean difference −0.24, 95% confidence internal [CI] −0.39–−0.09; participants=2531; RCTs=16; moderate CoE) or health-related quality of life (HRQOL) at 12 months (mean difference −0.12, 95% CI −0.25–0.02; participants=2004, RCTs=11; moderate CoE), compared to MTURP. BTURP probably reduces TUR syndrome (relative risk [RR] 0.17, 95% CI 0.09–0.30; participants= 6,745, RCTs=44; moderate CoE) and blood transfusions (RR 0.42, 95% CI 0.30–0.59; participants=5727, RCTs=38; moderate CoE), compared to MTURP. BTURP may carry similar risk of urinary incontinence at 12 months (RR 0.20, 95% CI 0.01–4.06; participants=751; RCTs=4; low CoE), re-TURP (RR 1.02, 95% CI 0.44–2.40; participants=652, RCTs=6, I2=0%; low CoE) and erectile dysfunction (International Index of Erectile Function [IIEF-5]) at 12 months (mean difference 0.88, 95% CI −0.56–2.32; RCTs=3; moderate CoE), compared to MTURP.ConclusionsBTURP and MTURP probably improve urological symptoms to a similar degree. BTURP probably reduces TUR syndrome and blood transfusion slightly postoperatively. The moderate certainty of evidence available for primary outcomes suggests no need for further RCTs comparing BTURP and MTURP.  相似文献   
8.
9.

Objectives:

To investigate whether electrolyte levels measured by using blood gas analyzers (ABG) and auto-analyzers (AA) are equivalent and can be used interchangeably.

Methods:

This observational prospective study was conducted in 100 patients admitted to the Intensive Care Unit, Adnan Menderes University School of Medicine, Aydin, Turkey, between March and August 2014. Samples for both AA and ABG analyzers were collected simultaneously from invasive arterial catheters of patients. The electrolyte levels were measured by using 2 methods.

Results:

The mean sodium level measured by ABG was 136.1±6.3 mmol/L and 137.8±5.4 mmol/L for AA (p=0.001). The Pearson’s correlation coefficient was 0.561 (p<0.001). The Bland-Altman 95% limits of agreement were -9.4 to 12.6 mmol/L. The mean potassium levels measured by ABG was 3.4±0.7 mmol/L and AA was 3.8±0.7 mmol/L (p=0.001). The Bland-Altman comparison limits were -0.58 to 1.24 and the associated Pearson’s correlation coefficient was 0.812 (p<0.001).

Conclusion:

The results of the 2 analyzing methods, in terms of sodium, were not equivalent and could not be used interchangeably. However, according to the statistical analyses results, by including, but not blindly trusting these findings, urgent and vital decisions could be made by the potassium levels obtained from the BGA, but a simultaneous follow-up sample had to be sent to the central laboratory for confirmation.Electrolytes are very important for the continuation of the physiological functions of the human body. They play vital roles in: regulation of the cell membrane potential, steady process of neurohormonal pathways, energy transformation and the fluid, and acid-base balance in the body. Signs and symptoms of electrolyte disorders may be nonspecific in an intensive care unit (ICU) patient.1-3 The therapies directed for maintaining vital organ functions affect the electrolyte balance. Consequently, electrolyte disorders are more common in critically ill patients than non-critically ill patients.1 The incidence of electrolyte disorders is nearly 25% in ICU patients.2 In recent studies,4-6 it is shown that in ICU patients, serum sodium and potassium levels are significant predictors of mortality. Therefore, prompt and complete correction of electrolyte disorders in ICU patients is vitally important. Under these circumstances, the importance of obtaining the results of serum electrolyte levels at the earliest is obvious. In routine application, serum electrolytes are measured by the indirect ion-sensing (ISE) method using auto-analyzers (AA) located in the central laboratories of hospitals. In this analyzing method, the processing time is longer because of a delay in the transportation of the samples to the central laboratory on account of several reasons.7 Hence, point-of-care (POC) testing methods, such as, arterial blood gas (ABG) analyzers have been increasingly used in the daily assessments of ICU patients. Blood gas analyzers; use the direct ISE method with short processing time that provides time and rapidity to the physician in the patient’s treatment decisions.7,8 The United States Clinical Laboratory Improvement Amendments (US CLIA) accepts a 0.5 mmol/l difference in the measured potassium levels and a 4 mmol/l difference in the measured sodium levels, in the gold standard measure of the standard calibration solution.9 In some recent studies, the data revealed the difference in the electrolyte levels between the ABG and AA results.10,11 Furthermore, there are also studies that suggest that there is no significant difference between these measuring methods.12,13 Physicians want to trust the veracity of the ABG results of electrolytes such as sodium and potassium because, by this method, the delay in reaching the results is surpassed, and risks arising from this delay may be reduced. However, the results of the above-mentioned studies are confusing and still a diagnostic challenge for physicians. On account of the hesitation by the physicians, we decided to investigate whether the sodium and potassium levels measured by using ABG and AA were equivalent. We conducted a prospective study comparing the electrolyte level results measured in the arterial blood samples by 2 different methods. We tried to notice all limitations of previous similar studies and designed our study according to these points. Thereby, we aimed to improve the accuracy of our study results.  相似文献   
10.
Context: Nonionic surfactant vesicles have gained increasing scientific attention for hydrophobic drugs delivery due to their biocompatibility, stability and low cost.

Objective: The aim of the present study was to synthesize and evaluate a novel creatinine-based nonionic surfactant in terms of its ability to generate biocompatible niosomal system for the delivery of Clarithromycin.

Materials and Methods: The surfactant was synthesized by reacting creatinine with lauroyl chloride followed by characterization using 1HNMR and MS. The drug-loaded niosomal vesicles of the surfactant were characterized for drug encapsulation efficiency (EE) using LC-MS, vesicle size using dynamic light scattering (DLS) and vesicle shape using atomic force microscopy (AFM). The surfactant was also investigated for blood hemolysis, in vitro cytotoxicity against different cell lines and in vivo acute toxicity in mice. Furthermore, the in vivo bioavailability of Clarithromycin encapsulated in the novel niosomal formulation was investigated using rabbits and quantified through validated LC-MS/MS method.

Results and discussion: Findings showed that vesicles were able to entrap up to 67.82?±?1.27% of the drug, and were rounded in shape with a size around 202.73?±?5.30?nm and low polydispersity. The surfactant caused negligible blood hemolysis, very low cytotoxicity and was found to be safe up to 2500?mg/kg body weight using mice. The niosomal formulation showed twofold enhanced oral bioavailability of Clarithromycin as compared to commercial formulations of the drug.

Conclusion: The study has shown that the creatinine-based niosomes developed in our laboratory were biocompatible, safe and increased the oral bioavailability of the model hydrophobic Clarithromycin using experimental animals.  相似文献   
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