bluuebunny/crossref_metadata_2025 huggingface dataset:
Use of contrast-enhanced post-mortem computed tomography to diagnose intestinal perforation caused by malpractice
Authors: Wang Zhuoqun , Ma Kaijun , Wan Lei , Zou Donghua , Liu Ningguo , Chen Yijiu
Published: April 2019

Rationale:

The application of post-mortem computed tomography (PMCT) and PMCT angiography (PMCTA) is becoming increasingly common in forensic investigations. One of the most frequently applied techniques today is PMCTA. However, few studies have focused on the application of contrast-enhanced PMCT of hollow organs such as the gastrointestinal tract. The intestine is a special digestive organ with a complicated anatomical structure; it is difficult to separate in medicolegal investigations, during which new rupture may occur, affecting the examiner's judgment. Moreover, the formalin-fixed intestine is more difficult to separate because of its increased brittleness. In the present case, the authors applied contrast-enhanced PMCT to the diagnosis of intestinal perforation caused by a medical accident.

Patient concerns:

A 67-year-old woman with cholecystitis underwent laparoscopic cholecystectomy in the hospital. The gallbladder was successfully removed, but the doctor was suspected to have accidentally perforated her intestinal tract with the laparoscopic machinery. The patient developed severe peritonitis and died after the operation.

Diagnosis, interventions, and outcomes:

Contrast-enhanced PMCT with isolation of the intestinal tract was performed after dissection of the body. The results suggested that the contrast agent flowed out through the rupture. The autopsy and histological examination revealed a perforated crevasse, confirming the cause of peritonitis while excluding other probabilities despite the doctor's denial.

Lessons:

Contrast-enhanced PMCT was an effective technique with which to interpret this gastrointestinal tract rupture and served as a non-invasive tool for identifying the injury.
The association between thyroid echogenicity and thyroid function in pediatric and adolescent Hashimoto's thyroiditis
Authors: Jeong Sun Hye , Hong Hyun Sook , Lee Ji Ye
Published: April 2019

In this study, we evaluated the association between thyroid echogenicity on ultrasonography (US) and thyroid function in pediatric and adolescent Hashimoto's thyroiditis (HT) patients.

In 86 pediatric and adolescent HT patients, the association between echogenicity and thyroid function and microsomal autoantibody status was evaluated. Among patients with overt hypothyroidism, 89.2% (33/37) showed a US grade of 3 or 4. All of the patients at grade 4 presented with overt hypothyroidism. In contrast, 97.8% (44/49) of the patients with subclinical hypothyroidism or euthyroidism showed grades 1 or 2. Patients with increased thyroid-stimulating hormone titer also tended to have increased US grades (P < .001). In contrast, free thyroxine levels were significantly decreased with increasing US grade (P < .001).

In conclusion, patients with higher US grades had decreased thyroid function (P < .001).
The value of diffusion tensor imaging for differentiating autism spectrum disorder with language delay from developmental language disorder among toddlers
Authors: Zhang Lin , Ma Rui , Yuan Yanran , Lian Dandan , Qi Xianlong , Zheng Ning , Li Kailong
Published: April 2019

Background:

Impaired language function is frequently observed as an initial sign in people with autism spectrum disorder (ASD). However, clinically, the early stages of ASD are difficult to distinguish from those of developmental language disorder (DLD).

Objective:

To evaluate the ability of diffusion tensor imaging (DTI) parameters for language-related white matter tracts (arcuate fasciculus) to differentiate ASD from DLD among toddlers.

Materials and methods:

We included 16 ASD toddlers with language delay and 18 DLD toddlers in this study. Magnetic resonance imaging sequences included T2-weighted imaging (T2WI), T1 3-dimensional magnetization-prepared rapid acquisition gradient-echo (3D MP-RAGE), and DTI. Tractography was performed using Neuro 3D in the Siemens Syngo Workstation, and fractional anisotropy (FA), average fiber length (AFL), tract volume (TV), and number of voxels (NV) were automatically calculated. Data were then analyzed using IBM SPSS Statistics 22.

Results:

The ASD group exhibited significantly lower FA values, as well as significantly higher TV and NV values compared with the DLD group. With age as the covariate, analysis of covariance revealed different significances in TV and NV. Analysis of variance for AFL revealed no significant differences between the 2 groups.

Conclusion:

DTI parameters of arcuate fasciculus were useful for differentiating ASD with language delay from DLD among toddlers. DTI has the potential to provide an objective and effective method for aiding early diagnosis, early intervention and improving long-term outcomes of ASD.
Low expression of PIK3C2A gene
Authors: Tan Buchuan , Liu Miao , Yang Yushuang , Liu Long , Meng Fanbo
Published: April 2019

Aims:

Phosphoinositide 3-kinases (PI3Ks) are a family of enzymes that phosphorylate the 3′-OH of inositol ring of phosphatidylinositol (PI) and regulate a broad range of signaling pathways. PIK3C2A is structurally distinct from the other members of this class and is expressed in endothelial cells, vascular endothelium, and smooth muscle. In ischemic cardiovascular diseases, such as coronary artery disease, pathology is associated with endothelial damage and inflammation, downregulation of the EPC cell population and function, and impaired angiogenesis. This study aims to make an assessment on whether expression of PIK3C2A gene can be used as a biomarker for predicting the risk of acute myocardial infarction (AMI).

Methods:

We collected peripheral blood from 84 subjects with non-coronary heart disease and 70 patients with AMI. The real-time quantitative PCR test was applied to measure levels of PIK3C2A gene expression at mRNA level in peripheral blood.

Results:

Our results indicated that the level of PIK3C2A gene expression in peripheral blood of AMI patients was significantly lower than one in the non-coronary heart disease subjects. Binary logistic regression analysis showed that low expression of PIK3C2A gene was an independent risk factor of AMI and increased the risk of AMI by 2.231 folds. Moreover, it was found that low expression of PIK3C2A gene was not associated with level of fasting blood glucose, platelet count, Gensini score of coronary artery, and quantity of cardiac troponin.

Conclusion:

The level of PIK3C2A gene expression in patients with AMI is significantly lower than that of healthy people. Low expression of PIK3C2A gene is an independent risk factor of AMI. Low expression of PIK3C2A could serve as a potential biomarker to predict risk of AMI.
PCSK9 positively correlates with plasma sdLDL in community-dwelling population but not in diabetic participants after confounder adjustment
Authors: Liu Yan , Wang Xiaona , Han Jie , Liu Lu , Jin Ying , Jin Liyuan , Ye Ping
Published: April 2019

This study aimed to investigate the relationship between plasma proprotein convertase subtilisin kexin 9 (PCSK9) and small dense low-density lipoprptein (sdLDL) in diabetic and non-diabetic participants in a community-dwelling cohort.

The plasma levels of PCSK9 and sdLDL were detected in 1766 participants (median age: 61.40 years; 733 males vs 1033 females; 383 diabetic vs 1383 non-diabetic patients) from the Pingguoyuan community of Beijing, China.

Results showed that Pearson correlation analysis revealed a positive correlation between PCSK9 and sdLDL (r = 0.263, P < .001). Multiple linear regression analysis showed a significant positive correlation between plasma PCSK9 and sdLDL in the whole population study. sdLDL was used as the dependent variable, and the potential cofounders were adjusted. However, any independent relationship was not observed between circulating PCSK9 and sdLDL in the diabetic subpopulation (r = 0.269, P < .05, β = 9.591, P > .05).

Thus, there is a positive correlation between plasma PCSK9 and sdLDL in a community-dwelling cohort, but not in type 2 diabetic subpopulation, after confounder adjustment.
Qian lie an suppository (prostant) for chronic prostatitis
Authors: Hui-juan Cao , Shi-bing Liang , Jian-ping Liu , Bin Wang , Hai-song Li , Ji-sheng Wang , Si-qi Guan , Yu-tian Zhu , Heng-heng Dai , Chun-yu Zhou
Published: April 2019

Background:

Chronic prostatitis (CP) is an inflammation of the prostate gland that seriously affects the quality of life of patients. The existing evidence of antibiotics and α-blockers for the treatment of CP is limited.

Objectives:

This review evaluated the effectiveness and safety of Qian Lie An Suppository (Prostant) in treating CP.

Methods:

Randomized controlled trials comparing Prostant (alone or plus the control) with placebo, conventional drugs, or nonpharmaceutical therapies for CP were included in this article through searching from 6 databases. Data were analyzed using RevMan 5.3 software. Meta-analysis was performed when the clinical or statistical heterogeneity was found acceptable among trials. Estimate effects were present with risk ratio (RR) or mean difference and their 95% confidence interval (CI) for dichotomies or continuous variables. Quality of the evidence for each primary outcome was assessed using GRADE criteria.

Results:

Totally 21 trials involving 3359 participants were included. There were 2 included trials had unclear risk of bias, and the remaining trials had high risk of bias. Meta-analyses showed the number of cured patients in the Prostant group was 2 times more than that of the placebo (RR 2.05, 95%CI 1.10 to 3.81) or antibiotics (RR 1.95, 95%CI 1.18 to 3.23) groups. Similar results were found when Prostant in combination with antibiotics or hyperthermia compared with the antibiotics (RR 1.78, 95% CI 1.10–2.89) or hyperthermia (RR 1.72, 95% CI 1.23–2.40) alone. However, there was no difference in the number of cured patients between Prostant and α-blockers or hyperthermia therapy. No severe adverse event was reported in all included trials. The main adverse events in Prostant group were reported (in 8 included trials) as diarrhea and anal discomfort.

Conclusions:

Low-quality evidence showed that the Prostant may have add-on effect for patients with CP on increasing the number of cured patients, relieving pain, and improving the quality of life. There is not sufficient evidence to determine the effectiveness and safety of Prostant for the treatment of CP compared with placebo, antibiotics, α-blockers or the hyperthermia therapy.
Identification of aberrantly methylated differentially expressed genes in age-related macular degeneration
Authors: Xu Zixuan , Ruan Zhaohui , Huang Xuetao , Liu Qiang , Li Zhaozhi , Zhou Xueyun , Zhang Xian , Shang Lei
Published: April 2019

DNA methylation plays a significant role in many diseases. Age-related macular degeneration (AMD) is a leading cause of vision loss for people aged 50 years and above, but the etiology and pathogenesis are largely unknown. This study aimed to identify the aberrantly methylated differentially expressed genes (DEGs) in AMD and predict the related pathways on the basis of public data.

Aberrant methylation can influence the functions of key genes by altering their expression. Here, we found out DEGs by overlapping public microarray data (GSE29801 and GSE102952). Functional and enrichment analyses of selected genes were performed using the DAVID database. Subsequently, protein–protein interaction (PPI) networks were constructed by using STRING and visualized in cytoscape to determine hub genes. Finally, we collected AMD patients’ blood samples to identify the methylation statuses of these hub genes by using methylated DNA immunoprecipitation.

In total, 156 hypermethylation-low expression genes and 127 hypomethylation-high expression genes were predicted. The hypermethylation-low expression genes were enriched in biological processes of response to cardiac conduction, ATP binding, and cell–cell junction assembly. The top 5 hub genes of the PPI network were HSP90AA1, HSPA1L, HSPE1, HSP90B1, and NOP56. Meanwhile, the hypomethylation-high expression genes were enriched in the biological processes of response to positive regulation of the MAPK cascade, actin cytoskeleton reorganization, dentate gyrus development, and cell migration. The top 5 hub genes of this PPI network were PIK3R1, EZR, IGF2, SLC2A1, and CDKN1C. Moreover, the methylation statuses of NOP56, EZR, IGF2, SLC2A1, CDKN1C were confirmed to be altered in the blood of AMD patients.

This study indicated possible aberrantly methylated DEGs and differentially expressed pathways in AMD by bioinformatics analysis, providing novel insights for unraveling the pathogenesis of AMD. Hub genes, including NOP56, EZR, IGF2, SLC2A1, CDKN1C, might serve as aberrant methylation-based candidate biomarkers for AMD in future applications.
Influence of OATP1B1 and OATP1B3 mutations and glomerular filtration rate on trough serum digoxin concentration in the Chinese population
Authors: Chen Shu-qing , Ding Wen-hui , Zhang Nan , Xiang Qian , Cui Yi-min , Zhao Xia
Published: April 2019

Polymorphisms of organic anion transporting polypeptides (OATPs) have been reported to affect trough serum digoxin concentration (SDC). However, the association of these polymorphisms with trough SDC in Chinese heart failure patients has not been studied. We aim to explore whether OATP1B1 388A>G, OATP1B1 521T>C, and OATP1B3 699G>A influence trough SDC in Chinese heart failure patients and to make clinical recommendations.

Chinese patients (n = 104) diagnosed with heart failure under long-term digoxin therapy (0.125 mg daily) were enrolled in this study. Blood samples were collected for the analysis of trough SDC (immunofluorescence) and the polymorphisms of OATP1B1 388A>G, OATP1B1 521T>C, and OATP1B3 699G>A (PCR-RFLP and Sanger sequencing).

Patients with glomerular filtration rate (GFR) under 30 mL/min had significantly higher trough SDC (1.20 ± 0.50 ng/mL) than recommended trough SDC for heart failure patients. Trough SDC was not significantly influenced by mutations of OATP1B1 388A>G (P = .890), 521T>C (P = .054), and OATP1B3 699G>A (P = .854). Patients with OATP1B1 521T>C mutant-type carrier had slightly higher trough SDC (0.98 ± 0.53 ng/mL) than those with wild-type carrier (0.74 ± 0.40 ng/mL) when they have repaired renal function.

Heart failure patients with severe renal dysfunction (GFR<60 mL/min) and/or OATP1B1 521T>C mutant-type carriers are recommended a smaller dosage of digoxin and strict therapeutic drug monitoring.
The effects of physical activity on executive function in children with attention-deficit/hyperactivity disorder
Authors: Zhang Mei-Qi , Liu Zhan , Ma Hong-Tao , Zhang Dong
Published: April 2019

Background:

The effects of physical activity on executive function are well documented, but whether physical activity contributes to the executive function of attention deficit hyperactivity disorder (ADHD) children are still inconclusive.

Methods:

The study is guided by the Preferred Reporting Items for Systematic Review and Meta-analysis Protocols (PRISMA-P). We will search the following databases PubMed, EMBASES, the Cochrane Library, CNKI, and Wanfang-Data to identify the Randomized Controlled Trials evaluating the effects of physical activity on executive function among ADHD children. The language of literature restricted in Chinese and English, which published from inception to January 2019. Two reviewers will screen the studies independently, while risk of bias assessment, data extraction, and inconsistent results will be discussed by the third reviewer. Revman 5.3 and Stata 12 software will be used to complete data analysis and synthesis.

Conclusion:

This study will be based on findings of previous studies, thus the ethics approval is not required. The final results will be presented at an international conference and submitted to a peer-reviewed journal of relative field for consideration of publication.

PROSPERO registration number:

CRD42019118622.
Protocol for a systematic review and meta-analysis of the efficacy of acupuncture and electroacupuncture against chemotherapy-induced peripheral neuropathy
Authors: Hwang Man-Suk , Lee Hye-Yoon , Lee Jin-Hyun , Choi Tae-Young , Lee Jung-Han , Ko Youn-Seok , Choi Sung-Youl , Park Tae-Yong
Published: April 2019

Introduction:

Chemotherapy-induced peripheral neuropathy (CIPN) occurs in approximately 30% to 40% of patients who receive chemotherapy; however, standardized treatment for CIPN has not yet been developed. Acupuncture is widely used to treat CIPN in Korea, but its efficacy has not been investigated. The purpose of this study is to review the current literature on the efficacy of acupuncture and electroacupuncture (EA) in treating CIPN.

Materials and Methods:

We will perform a literature review using the relevant databases, including MEDLINE, Embase, the Allied and Complementary Medicine Databases (AMED), and China National Knowledge Infrastructure (CNKI), as well as Korean databases, including the National Digital Science Library (NDSL), Oriental Medicine Advanced Searching Integrated System (OASIS), DBpia, and Korean studies Information Service System (KISS). Randomized controlled trials describing treatment of CIPN symptoms with acupuncture or EA will be included. The primary outcomes will be scores on a visual analog scale and a numeric rating scale for neuropathic pain. We will also assess the risk of bias by evaluating the available studies using the tools of the Cochrane Collaboration and carry out a meta-analysis.

Ethics and dissemination:

Ethical approvals and patient consent are not necessary because the meta-analysis will be based on published research. We will submit our meta-analysis to a peer-reviewed journal for publication.

PROSPERO registration number:

CRD42018111509
Responsiveness of the modified lower extremity functional scale in patients with low back pain and sciatica
Authors: Horng Yi-Shiung , Hou Wen-Hsuan , Liang Huey-Wen
Published: April 2019

We tested the responsiveness of the modified Lower Extremity Functional Scale (LEFS) for patients with low back pain (LBP) and sciatica and made a comparison with the modified Roland-Morris Disability Scale for sciatica (RMS-L) and self-reported pain intensity measured by visual analogue scale (VAS).

One hundred and forty-eight participants were recruited from 2 university hospitals. The evaluation included demographic data, LBP history, and the modified LEFS, RMS-L, and VAS, with a follow-up one month later. Several responsiveness statistics were calculated.

The study followed 132 participants, approximately 25% reported improvement. Guyatt responsiveness index (GRI) was 0.8 or higher for 3 measures, while standardized response means were 0.8 or higher for the RMS-L and VAS, but only 0.6 for the modified LEFS among improved group. According to ROC analysis, the modified LEFS had an area under curve (AUC) similar to that of the modified RMS-L, but significantly smaller than that of the VAS.

The responsiveness of the modified LEFS was moderate but not superior to the VAS or RMS-L. Although, the modified LEFS could not replace the RMS-L or VAS, it could still be used as a complementary measure since these three measurements covered different body function, activity and participation domains.
Effects of a multifaceted individualized pneumoperitoneum strategy in elderly patients undergoing laparoscopic colorectal surgery
Authors: Liu Liping , Lv Na , Hou Chunmiao
Published: April 2019

Background:

Laparoscopic colorectal surgery may adversely affect respiration, circulation, and acid-base balance in elderly patients, owing to the relatively long duration of CO2 absorption. We conducted this retrospective study to determine the safety and efficacy of warmed, humidified CO2 pneumoperitoneum in elderly patients undergoing laparoscopic colorectal surgery.

Methods:

We enrolled 245 patients between January 2016 and August 2018.

The experimental group (warming and humidification group [WH]) received warmed (37°C), humidified (98%) insufflation of CO2, and the control group (cold, dry CO2/control group [CD]) received standard CO2 (19°C, 0%). All other aspects of patient care were standardized. Intraoperative hemodynamic data, arterial blood pH, and lactic acid levels were recorded. We also recorded intra-abdominal pressure, incidence of shivering 1 hour after surgery, satisfaction scores of patients and surgeons 24 hours after surgery, times to first flatus/defecation, first bowel movement, and tolerance of semiliquid food, discharge time, and incidence of vomiting, diarrhea, and surgical site infections.

Results:

Compared with the WH group, heart rate and mean arterial pressure were significantly higher from T3 to T8 (P < .05), lactic acid levels were significantly higher from T4 to T9 (P < .05), and recovery time in the post-anesthesia care unit (PACU) was significantly longer in the CD group (P < .05). Patient and surgeon satisfaction scores were significantly higher in the WH group than the CD group (P < .05). In addition, the times to first flatus/defecation and bowel movement were significantly longer in the CD group (P < .05). No significant differences were noted between the groups in the time to tolerance of semiliquid food and time of discharge (P > .05). The incidence of vomiting, diarrhea, and shivering was significantly lower in the WH group (P < .05). The number of patients with a shivering grade of 0 was significantly higher in the WH group, whereas the number with a shivering grade of 3 was significantly higher in the CD group (P < .05).

Conclusion:

Warmed, humidified insufflation of CO2 in elderly patients undergoing laparoscopic colorectal surgery could stabilize hemodynamics, and reduce lactic acid levels, recovery time in the PACU, and the incidence of acute gastrointestinal injury-related symptoms.
Efficacy and safety of once daily versus twice daily mesalazine for mild-to-moderate ulcerative colitis
Authors: Zheng Xin , Zhang Zhen , Wang Botao , Li Jiaxin , Qiu Chongyang , Zhang Qi , Wang Ximo
Published: April 2019

Background:

We aimed to conduct a meta-analysis to evaluate the efficacy and safety between once daily (OD) and twice daily (BD) regime dosing of mesalazine for mild-to-moderate ulcerative colitis (UC).

Methods:

PubMed, Embase, the Cochrane library, and Web of Science from 1990 to November 2018 were investigated. We searched randomized controlled trials (RCTs) comparing OD with BD regime dosing of mesalazine for mild-to-moderate UC. The software Review Manager 5.3 was used to pool the risk ratio (RR) with a 95% confidence interval (CI).

Results:

Eight RCTs containing 3495 patients were identified. Regardless of induction of remission or maintenance of remission of UC, OD regime dosing of mesalazine was as effective as BD regime dosing in clinical and endoscopic remission and clinical remission. Also, no obvious difference was found between OD and BD regime dosing of mesalazine regardless of total adverse events, treatment-related adverse events or serious adverse events.

Conclusion:

OD is as effective and safe as BD regime dosing of mesalazine for active UC.
Current screening practice in patients under long-term hydroxychloroquine medication in Taiwan
Authors: Yen Chu-Yu , Lee Pei-Hsuan , Yen Ju-Chuan , Chen Chun-Chen , Hu Hsiao-Yun , Tseng Po-Chen
Published: April 2019

Hydroxychloroquine (HCQ), an analog of chloroquine, is widely used in various rheumatologic and dermatologic disorders. However, it may cause severe retinopathy with long-term use. The guidelines proposed by the American Academy of Ophthalmology suggested a baseline fundus examination and an annual screening after 5 years by using automated visual fields (VF) plus spectral-domain optical coherence tomography (SD-OCT). Both multifocal electroretinogram (mfERG) and fundus autofluorescence (FAF) can also be used to improve the accuracy of diagnosis. The purpose of this study was to examine if the current HCQ screening practice in Taiwan was sufficient according to the guidelines to prevent severe macular complications.

This study could remind every doctor to explain visual side effects thoroughly to every patient using HCQ, and refer patients for the ophthalmologic survey to eliminate potential visual impairment caused by this medicine.

This nationwide population-based cohort study included all patients who started taking HCQ (n = 5826) from January 1, 1997, to December 31, 2007, in the Longitudinal Health Insurance Database 2000. The ICD codes used for HCQ retinopathy were 362.10, 362.55, 362.89, and 362.9. Patients previously diagnosed these retinal disorders were excluded. Demographic data including sex, age, diagnostic tools used, and the date of the initial diagnosis of the subsequent HCQ-related retinal disorder were collected. Patients were divided into 2 groups. The patients taking HCQ <5 years were defined as group 1, and >5 years as group 2. The risk of developing retinal diseases between these 2 groups was compared with a 2-sample t-test for continuous variables, and Fisher's exact test for discrete variables. Multiple logistic regressions were used for odds ratio calculation.

The baseline examination ratio of the automated VF, SD-OCT scans, and multifocal electroretinograms (mfERGs) in the first 3 months were only 0.2% in both groups. The screening ratio of the 3 examination tools after 5 years were 1.1% in group 1 and 1.2% in group 2. 2.5% and 3.9% of patients developed a retinal disorder after HCQ use in group 1 and 2, respectively. The risk of developing retinal disorder was significantly higher in group 2 (relative risk = 1.53, P = .006). The odds ratio (OR) was also significantly higher in group 2 (1.67 with 95% cumulative incidence 1.20–2.30)

The examination ratio according to the guidelines was very low in Taiwan. Thus, it is very important for doctors who prescribe HCQ to schedule both baseline and annual ophthalmology screening tests and inform patients of possible severe ocular complications, even in the patient taking HCQ <5 years. It is also important for ophthalmologists to review medical history carefully to find out the causes of retinotoxicity. Medications should be stopped, if possible when toxicity is recognized or strongly suspected.
Should We Use Tegaserod for Irritable Bowel Syndrome?
Authors: Marciniak Thomas A. , Serebruany Victor
Published: April 2019

Background:

Tegaserod, a serotonin (5-HT4) agonist initially approved for constipation but withdrawn from use in 2007 because of concerns about cardiovascular adverse effects, was resubmitted to the Food and Drug Administration (FDA) in 2018 for use in a restricted population.

Areas of Uncertainty:

Despite an 18-year regulatory history, there remain pharmacology and clinical trial concerns that have not been addressed but are critical for proper assessment of the drug safety and efficacy profile.

Sources:

Original FDA reviews, FDA and developer advisory committee briefing documents, and published literature.

Results:

The major pharmacology concern is that the fate and effects of half of the molecule, the pentylaminoguanidine moiety, are unknown. There is evidence that pentylaminoguanidine may contribute to both efficacy and safety. There are other metabolites that are poorly characterized, and potential receptor interactions that suggest cardiovascular effects are possible. The major clinical trial concern is that, while the trial data support a low but definite cardiovascular risk, both subject follow-up and cardiovascular event descriptions were incomplete such that an accurate estimate of cardiovascular risk is not possible.

Conclusions:

The uncertainties and lack of reliable evidence regarding tegaserod metabolism and cardiovascular risk estimates may discourage clinical use. Signals for cardiovascular toxicity in typical drug development programs are subtle and must be pursued aggressively, with complete case follow-up and cardiovascular event capture in the clinical trials.
Dysphagia in patients with non-head and neck cancer
Authors: Frowen Jacqui
Published: April 2019

Purpose of review

To review the current evidence on dysphagia in non-head and neck cancer, including its cause, prevalence, impact, management, and areas for future research.

Recent findings

Dysphagia is widely recognised as a common and debilitating side-effect of head and neck cancer (HNC) and its treatment; however, minimal attention has been given to dysphagia in other cancer populations. Detailed data regarding the exact nature and prevalence of dysphagia are limited, in part because of the lack of any validated tools specifically for non-HNC patients. Dysphagia can be due to a variety of different causes in cancer patients. It can have a significant impact on physical and psychological wellbeing, and its management can be complex and multifactorial.

Preliminary evidence suggests that the prevalence of dysphagia in non-HNC patients may be high. Cancer patients are vulnerable and survivorship is a key component of cancer care, so further research is essential to better understand the problem and thus provide optimal care and outcomes for patients.
Chronic lung allograft dysfunction: light at the end of the tunnel?
Authors: Verleden Stijn E. , Vos Robin , Verleden Geert M.
Published: April 2019

Purpose of review

Chronic lung allograft dysfunction (CLAD) has been recently introduced as an umbrella-term encompassing all forms of chronic pulmonary function decline posttransplant with bronchiolitis obliterans syndrome and restrictive allograft syndrome as the most important subtypes. Differential diagnosis and management, however, remains complicated.

Recent findings

Herein, we provide an overview of the different diagnostic criteria (pulmonary function, body plethysmography and radiology) used to differentiate bronchiolitis obliterans syndrome and restrictive allograft syndrome, their advantages and disadvantages as well as potential problems in making an accurate differential diagnosis. Furthermore, we discuss recent insights in CLAD management and treatment and advances in the search for accurate biomarkers of CLAD.

Careful dissection of CLAD phenotypes is of utmost importance to assess patient prognosis, but uniform diagnostic criteria are desperately needed. There is a long way ahead, but the first steps towards this goal are now taken; tailored individualized therapy will be the golden standard to treat CLAD in the future, but randomized placebo-controlled and multicentre trials are needed to identify new and powerful therapeutic agents.
Chronic Asymptomatic Pancreatic Hyperenzymemia
Authors: Amodio Antonio , De Marchi Giulia , Granato Anna , de Pretis Nicolò , Gabbrielli Armando , Manfredi Riccardo , Pozzi Mucelli Roberto , Frulloni Luca
Published: April 2019

Objectives

Chronic asymptomatic pancreatic hyperenzymemia (CAPH) was described as a benign disease. However, we already described clinically relevant findings requiring surgery or follow-up in half of the subjects. The aim of this study was to evaluate the long-term outcome of CAPH in terms of symptoms and evolution toward chronic pancreatitis.

Methods

Subjects previously enrolled in the first phase of the study (from 2005 to 2010) were reinvestigated from December 2013 to January 2017 with a phone call ± magnetic resonance cholangiopancreatography with secretin stimulation.

Results

A total of 133 subjects were eligible for the follow-up study (75 males, 58 females; age, 48.4 [standard deviation {SD}, 14] years); 24 (18%) of them dropped out. During a mean follow-up of 9.3 (SD, 5.2) years after the first diagnosis of CAPH, no episode of acute pancreatitis or abdominal pain was reported. Sixty-three subjects (58%) of 109 underwent magnetic resonance cholangiopancreatography with secretin stimulation with a mean follow-up of 5.7 [SD, 3.1] years (range, 1–11 years). Secretin stimulation-MRCP resulted unchanged in 54 (90%) of 60 subjects, worsened in 3 (5%) and improved in 3 (5%). Two subjects died from causes unrelated to pancreatic disease.

Conclusions

Excluding subjects with a pancreatic disease at index magnetic resonance imaging, CAPH is a benign condition.
Addressing Spiritual and Religious Influences in Care Delivery
Authors: LeDoux Jeannie , Mann Chikita , Demoratz Michael , Young Jared
Published: April 2019

Purpose:

The impact of spiritual and religious factors on health and care delivery has been identified in case management field research. The purpose of this article is to examine how case managers, taking a holistic, patient-centered approach, are required under professional and ethical standards to address the spiritual and religious influences that may impact the individual's health, care choices, and care delivery.

Primary Practice Settings:

Case managers across health or human services must be able to identify and address the spiritual and/or religious factors that may influence a care plan and care delivery. This includes case managers in acute care, primary care, workers' compensation, hospice, mental health counseling, and other practice settings. Regardless of their professional discipline, specialization, or practice setting, case managers must ensure that the voice of the individual is heard and that each person receives the support that is most relevant and meaningful.

Implementations for Case Management Practice:

The impact of spiritual and religious factors on health and care delivery has been identified in case management field research, known as role and function studies, which are conducted every 5 years, and which set the blueprint for the Certified Case Manager (CCM) certification examination. The most recent role and function study affirmed the knowledge domain of multicultural, spiritual, and religious factors that may affect the health status of the individual receiving case management services. Essential activities of case management include identifying multicultural, spiritual, and religious factors that may affect the client's health status and incorporating the effects of the client's multicultural, spiritual, and religious factors in the development of the plan of care and service delivery (H. Tahan, A. Watson, & P. Sminkey, 2016). To demonstrate competency in the required knowledge domain and essential activities, case managers must be able to identify and address the spiritual and/or religious factors that may influence a care plan and care delivery.
Mismatch Repair Deficiency Identifies Patients With High-Intermediate–Risk (HIR) Endometrioid Endometrial Cancer at the Highest Risk of Recurrence: A Prognostic Biomarker
Authors: Backes Floor J. , Haag Jennifer , Cosgrove Casey M. , Suarez Adrian , Cohn David E. , Goodfellow Paul J.
Published: April 2019

(Abstracted from Cancer 2019;125:398–405)

More than 70% of patients diagnosed with endometrial cancer (EC) are stage I, and such early-stage disease has good outcomes, with reported 5-year survival rates of 90%. However, a small subgroup has been identified—the so-called high-intermediate–risk (HIR) EC—which has relatively high local and distant recurrence rates, resulting in poor survival.
Association of Sexually Transmitted Diseases With Cervical Ectopy: A Systematic Review
Authors: Soares Leila Cristina , Braz Fernanda Lehrer Turbae Amaral , Araújo Amanda Rodrigues , Oliveira Marco Aurélio Pinho
Published: April 2019

Objective

The aim of this study was to review the available literature to explore evidence indicating an association between cervical ectopy and sexually transmitted diseases, which could help in the decision to treat or not to treat this condition.

Methods

A review of the literature was conducted using the PubMed, EMBASE and clinicaltrials.gov databases on ectopy of the cervix using the terms “ectopy OR ectropium AND cervix” filtered only by language, without limit of date. A total of 71 studies were found in the initial selection, of which 56 were deleted by title, abstract, or full text. The remaining 15 articles were analyzed in this study.

Results

Cervical ectopy showed a positive association with human papillomavirus, human immunodeficiency virus, bacterial vaginosis, cervical epithelial atypia, postcoital bleeding, and desquamative inflammatory vaginitis. High-quality studies reported no association between ectopy and chlamydia infection. It was also not associated with gonococcal infection and herpes simplex.

Conclusions

Cervical ectopy shows a probable association with increased acquisition of some sexually transmitted diseases. Additional studies are required to confirm the possible beneficial effects of treatment and to evaluate the possible complications of these treatments.
Treatment Outcomes of Stenotrophomonas maltophilia Bacteremia in Critically Ill Children: A Multicenter Experience
Authors: Tokatly Latzer Itay , Nahum Elhanan , Cavari Yuval , Lazar Isaac , Ben-Ari Yossi , Ben-Shimol Shalom , Ben-Shalom Gal , Geffen Yuval , Goldberg Lior , Rubinstein Marina , Keller Nathan , Pessach Itai M. , Paret Gideon
Published: April 2019

Objectives

: Stenotrophomonas maltophilia is a gram-negative opportunistic bacterium that may cause a myriad of clinical diseases in immunocompromised individuals. We aimed to describe the clinical characteristics, risk factors, mortality, and treatment of S. maltophilia bacteremia in critically ill children, a topic on which data are sparse.

Design:

A multicenter observational retrospective study in which medical charts of critically ill children with S. maltophilia bacteremia were reviewed between 2012 and 2017.

Setting:

Data were collected from each of the four largest PICUs nationwide, allocated in tertiary medical centers to which children with complex conditions are referred regularly.

Patients:

A total of 68 suitable cases of S. maltophilia bacteremia were retrieved and reviewed.

Measurements and Main Results:

The total occurrence rate of S. maltophilia isolation had increased significantly during the study period (r = 0.65; p = 0.02). The crude mortality was 42%, and the attributed mortality was 18%. Significant risk factors for mortality were a longer length of hospital stay prior to infection (33 d in nonsurvivors vs 28 in survivors; p = 0.03), a nosocomial source of infection (p = 0.02), presentation with septic shock (p < 0.001), and treatment with chemotherapy (p = 0.007) or carbapenem antibiotics (p = 0.05) prior to culture retrieval. On multivariate analysis, septic shock (odds ratio, 14.6; 95% CI, 1.45–147.05; p = 0.023) and being treated with chemotherapy prior to infection (odds ratio, 5.2; 95% CI, 1.59–17.19; p = 0.006)] were associated with mortality. The combination of ciprofloxacin, trimethoprim-sulfamethoxazole, and minocycline resulted in the longest survival time (p < 0.01).

Conclusions:

The significant attributed mortality associated with S. maltophilia bacteremia in critically ill children calls for an aggressive therapeutic approach. The findings of this investigation favor a combination of trimethoprim-sulfamethoxazole, ciprofloxacin, and minocycline.
Relationship Between Different Experimental Measures of Distorted Symptom Perception in Functional Syndrome Patients
Authors: Van Den Houte Maaike , Van Oudenhove Lukas , Bogaerts Katleen , Van Diest Ilse , De Bie Jozef , Persoons Philippe , Van den Bergh Omer
Published: April 2019

Objective

Patients with functional somatic syndromes show reduced correspondence between induced physiological changes and self-reported symptoms in a rebreathing paradigm, as well as elevated symptoms unrelated to physiological changes after induction of negative affective states in an affective picture-viewing paradigm. Detailed results of both paradigms separately were published elsewhere. The main goal of the current report is to describe the relationship between the responses to these two paradigms measuring distortions in symptom perception in a well-described sample of patients with fibromyalgia and/or chronic fatigue syndrome.

Methods

Patients (N = 81) with fibromyalgia and/or chronic fatigue syndrome participated in a test session comprising four well-validated paradigms, including the picture-viewing and rebreathing paradigm. Using mixed model analyses, we tested whether the amount of affective modulation of symptom reporting was related to distorted perception of induced dyspnea. In an exploratory way, we assessed the role of several individual difference variables as moderators.

Results

There was no relationship between patients' amount of affective modulation of symptom reporting, as assessed with the picture paradigm, and level of distortion in dyspnea perception, as assessed with the rebreathing paradigm (effect of affective modulation in the subjective recovery from induced dyspnea: F
1,70 = 0.16, p = .70; time by affective modulation interaction effect: F
4,70 = 0.14, p = .97).

Conclusions

Biased symptom reporting in one paradigm is unrelated to biased symptom reporting in the other paradigm, indicating that distortions in symptom perception in patients with functional somatic syndromes are not a trait-like, cross-situationally stable condition, but a versatile dysfunction that is context dependent.
Gender Affirmation Surgery From a Public Health Perspective: Advances, Challenges, and Areas of Opportunity
Authors: Williams Eva A. , Patete Carissa L. , Thaller Seth R.
Published: April 2019

Gender affirmation surgery (GAS) is sought out by approximately 20 to 40% of transgender individuals. These patients possess unique mental and physical health needs. These are compounded by prejudices and lack of education about transgender individuals within the medical system and society at large. Societal and medical barriers are associated with increased risks of violence, suicide, and sexually transmitted infections. This combination of high medical needs and barriers to accessing appropriate care may give rise to a self-perpetuating cycle of risk exposure, stigmatization, prejudice, and eventually poor health outcomes. It is imperative that plastic and reconstructive surgeons understand GAS from a public health perspective, so that they may provide the highest quality of care and help alleviate these disparities. The authors describe unique public health topics in GAS. These are specifically related to healthcare access, surgical education, cultural sensitivity, as well as mental health outcomes for patients who undergo GAS.
Low-Cost Desktop-Based Three-Dimensional-Printed Patient-Specific Craniofacial Models in Surgical Counseling, Consent Taking, and Education of Parent of Craniosynostosis Patients: A Comparison With Conventional Visual Explanation Modalities
Authors: Alshomer Feras , AlFaqeeh Faisal , Alariefy Mohammed , Altweijri Ikhlass , Alhumsi Taghreed
Published: April 2019

Background:

Craniosynostosis is a complex craniofacial deformity. Surgical decision, if needed, is always hard on the parent and requires the use of multimodalities of explanation. To the authors’ knowledge, there have been no studies tackling family counseling about the deformity and surgical decision-making process with the use of low-cost patient-specific three-dimensional (3D)-printed models.

Methods:

A cross-sectional study investigating the utility of patient-specific 3D-printed models using a desktop-based 3D printer. Questionnaire was constructed and validated screening the demographics, knowledge, expectation, and surgical decision-making process supplied using Likert. Data were collected consecutively from each parent first after explanation with conventional 3D computed tomography (CT) images, and then repeated after the 3D-printed model has been presented.

Results:

Fourteen parents were screened. Majority of parents considered the pathology to have a potential effect of child's functional and aesthetic outcomes. After using the 3D-printed models, the participants had a clear vision and needed not to read any more about the condition (P = 0.05, P = 0.019, respectively). Agreement for surgical management was in favor of the 3D-printed models compared with CT images (P = 0.028). Explanation with CT images yielded higher mean score in knowledge about potential complications compared with 3D models (P value = 0.007). For the 3D models, average printing time was 26 hours, and a mean cost of 5.2$.

Conclusion:

The utility of desktop 3D printing is an affordable modality to provide adequate information about craniosynostosis and can assist surgical decision-making. Knowledge and adaptation of such cheap technology represents a great skill aiding clinical practice.
Identification of Plasma Proteome Signatures Associated With Surgery Using SOMAscan
Authors: Fong Tamara G. , Chan Noel Y. , Dillon Simon T. , Zhou Wenxiao , Tripp Bridget , Ngo Long H. , Otu Hasan H. , Inouye Sharon K. , Vasunilashorn Sarinnapha M. , Cooper Zara , Xie Zhongcong , Marcantonio Edward R. , Libermann Towia A.
Published: April 2019

Objectives:

To characterize the proteomic signature of surgery in older adults and association with postoperative outcomes.

Summary of Background Data:

Circulating plasma proteins can reflect the physiological response to and clinical outcomes after surgery.

Methods:

Blood plasma from older adults undergoing elective surgery was analyzed for 1305 proteins using SOMAscan. Surgery-associated proteins underwent Ingenuity Pathways Analysis. Selected surgery-associated proteins were independently validated using Luminex or enzyme-linked immunosorbent assay methods. Generalized linear models estimated correlations with postoperative outcomes.

Results:

Plasma from a subcohort (n = 36) of the Successful Aging after Elective Surgery (SAGES) study was used for SOMAscan. Systems biology analysis of 110 proteins with Benjamini-Hochberg (BH) corrected P value ≤0.01 and an absolute foldchange (|FC|) ≥1.5 between postoperative day 2 (POD2) and preoperative (PREOP) identified functional pathways with major effects on pro-inflammatory proteins. Chitinase-3-like protein 1 (CHI3L1), C-reactive protein (CRP), and interleukin-6 (IL-6) were independently validated in separate validation cohorts from SAGES (n = 150 for CRP, IL-6; n = 126 for CHI3L1). Foldchange CHI3L1 and IL-6 were associated with increased postoperative complications [relative risk (RR) 1.50, 95% confidence interval (95% CI) 1.21–1.85 and RR 1.63, 95% CI 1.18–2.26, respectively], length of stay (RR 1.35, 95% CI 0.77–1.92 and RR 0.98, 95% CI 0.52–1.45), and risk of discharge to postacute facility (RR 1.15, 95% CI 1.04–1.26 and RR 1.11, 95% CI 1.04–1.18); POD2 and PREOP CRP difference was associated with discharge to postacute facility (RR 1.14, 95% CI 1.04–1.25).

Conclusion:

SOMAscan can identify novel and clinically relevant surgery-induced protein changes. Ultimately, proteomics may provide insights about pathways by which surgical stress contributes to postoperative outcomes.
Single-cell Transcriptomics and Solid Organ Transplantation
Authors: Malone Andrew F. , Humphreys Benjamin D.
Published: April 2019

Single-cell RNA sequencing (scRNA-seq) allows the measurement of transcriptomes from individual cells providing new insights into complex biological systems. scRNA-seq has enabled the identification of rare cell types, new cell states, and intercellular communication networks that may be masked by traditional bulk transcriptional profiling. Researchers are increasingly using scRNA-seq to comprehensively characterize complex organs in health and disease. The diversity of immune cell types, some present at low frequency, in a transplanted organ undergoing rejection makes scRNA-seq ideally suited to characterize transplant pathologies because it can quantify subtle transcriptional differences between rare cell types. In this review, we discuss single-cell sequencing methods and their application in transplantation to date, current challenges, and future directions. We believe that the remarkably rapid pace of technological development in this field makes it likely that single-cell technologies such as scRNA-seq will have an impact on clinical transplantation within a decade.