bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical Practice Guidelines and Consensus Statements About Pain Management in Critically Ill End-of-Life Patients: A Systematic Review
Authors: Durán-Crane Alejandro , Laserna Andrés , López-Olivo María A. , Cuenca John A. , Díaz Diana Paola , Cardenas Yenny Rocío , Urso Catherine , O’Connell Keara , Azimpoor Kian , Fowler Clara , Price Kristen J. , Sprung Charles L. , Nates Joseph L.
Published: September 2019

Objectives:

To identify and synthesize available recommendations from scientific societies and experts on pain management at the end-of-life in the ICU.

Data Sources:

We conducted a systematic review of PubMed, EMBASE, the Cochrane Database of Systematic Reviews, and Biblioteca Virtual en Salud from their inception until March 28, 2019.

Study Selection:

We included all clinical practice guidelines, consensus statements, and benchmarks for quality.

Data Extraction:

Study selection, methodological quality, and data extraction were performed independently by two investigators. A quality assessment was performed by four investigators using the Appraisal of Guidelines for Research and Evaluation II instrument. The recommendations were then synthesized and categorized.

Data Synthesis:

Ten publications were included. The Appraisal of Guidelines for Research and Evaluation II statement showed low scores in various quality domains, especially in the applicability and rigor of development. Most documents were in agreement on five topics: 1) using a quantitative tool for pain assessment; 2) administering narcotics for pain relief and benzodiazepines for anxiety relief; 3) against prescribing neuromuscular blockers during withdrawal of life support to assess pain; 4) endorsing the use of high doses of opioids and sedatives for pain control, regardless of the risk that they will hasten death; and 5) using quality indicators to improve pain management during end-of-life in the ICU.

Conclusions:

In spite of the lack of high-quality evidence, recommendations for pain management at the end-of-life in the ICU are homogeneous and are justified by ethical principles and agreement among experts. Considering the growing demand for the involvement of palliative care teams in the management of the dying patients in the ICU, there is a need to clearly define their early involvement and to further develop comprehensive evidence-based pain management strategies. Based on the study findings, we propose a management algorithm to improve the overall care of dying critically ill patients.
Fluid intake and clinicopathological characteristics of bladder cancer: the West Midlands Bladder Cancer Prognosis Programme
Authors: van Hensbergen Mitch , van Osch Frits H.M. , Jochems Sylvia , James Nicholas D. , Wallace D. Michael A. , Wesselius Anke , Cheng K.K. , Bryan Richard T. , Zeegers M.P.
Published: September 2019

Objective

Between 10 and 20% of bladder cancer patients who are diagnosed with nonmuscle-invasive bladder cancer will progress to muscle-invasive disease. Risk of progression depends on several factors at diagnosis including age, tumour stage, grade, size and number, and the presence or absence of carcinoma in situ. Fluid intake may be related to these factors.

Methods

Data of 1123 participants from the West Midlands Bladder Cancer Prognosis Programme were used. Data collection was via a semistructured questionnaire, and case report forms were used to collect clinicopathological data. Fluid intake was measured for six main categories: alcoholic fluids, hot fluids, fruit fluids, milk, fizzy drinks, and water, and converted into quintile variables. Multilevel mixed-effects linear regression was performed for every beverage category per clinicopathological variable and corrected for age, gender, and smoking status.

Results

Age at diagnosis was distributed differently amongst those in different total fluid intake quintiles (predicted means 71.5, 70.9, 71.5, 69.9, and 67.4, respectively) and showed a significant inverse linear trend in alcohol (P < 0.01), hot fluids (P < 0.01), and total fluids intake (P < 0.01), in nonmuscle-invasive bladder cancer patients.

Conclusion

Our results suggest an inverse association for alcohol intake and total fluid intake with age at diagnosis. These results should be confirmed by future studies, alongside a possible (biological) mechanism that could influence tumour growth, and the effect of micturition frequency.
Noninvasive Hemodynamic Monitoring of Cocaine-Induced Changes in Cardiac Output and Systemic Vascular Resistance in Subjects With Chronic Cocaine Use Disorder
Authors: Van Tassell Benjamin W. , Westman Peter , Trankle Cory , Johns Sade , Kadariya Dinesh , Buckley Leo , Carbone Salvatore , Abbate Antonio , Moeller Frederick Gerard
Published: September 2019

Background:

Cocaine use disorder (CUD) is a common problem in the United States and worldwide. The mechanisms by which cocaine induces acute cardiovascular toxicity are various. When systemically absorbed through inhaled or intravenous routes, cocaine induces an acute rise in the heart rate (HR) and blood pressure (BP) leading to a significant increase in the cardiac output (CO) and myocardial oxygen demand. Subjects with chronic CUD represent a special population that has experienced long-term cocaine exposure, often without showing signs of cardiovascular disease. We herein present prospectively collected data on the acute hemodynamic effects of intravenous cocaine in a cohort of nontreatment-seeking individuals with CUD without cardiovascular disease.

Methods and Results:

Baseline physiologic data were collected while participants underwent infusion of escalating doses of cocaine (10, 20, and 40 mg administered over 2 minutes) at baseline and after receiving single-blind placebo treatment. Continuous noninvasive hemodynamic monitoring was performed throughout the infusion sessions using the ccNexfin finger cuffs (Edwards Lifesciences Corp, Irvine, CA). The recorded arterial BP tracings allowed for the measurement of beat-to-beat changes in HR, BP, stroke volume, CO, and systemic vascular resistance (SVR). None of the subjects experienced a treatment-related serious adverse event. Cocaine produced significant dose-dependent increases in median HR, BP, CO, and +dP/dt (a measure of cardiac contractility) and a significant dose-dependent reduction in median SVR.

Conclusions:

Intravenous cocaine in a cohort of otherwise healthy subjects with CUD produced dose-dependent increases in CO, largely explained by an increase in HR, accompanied by a dose-dependent decrease in SVR.
Demodex-Mite Infestation in Cilia and its Association With Ocular Surface Parameters in Japanese Volunteers
Authors: Mizuno Miki , Kawashima Motoko , Uchino Miki , Suzuki Natsume , Mitamura Hiroto , Uchino Yuichi , Yokoi Norihiko , Tsubota Kazuo
Published: September 2019

Objectives:

To investigate the presence of Demodex mites on the eyelashes of a Japanese population and to explore its associations with subjective ocular symptoms and clinical ocular surface signs, including lid margin findings and fluorescein breakup time (FBUT).

Methods:

Sixty-three Japanese Tokyo-based volunteers were examined (24 men and 39 women; mean±SD of age, 50.6±15.8 years). Eyelash sampling was performed by epilating three lashes from the center of the right upper eyelid. Eyelashes were tested for Demodex mites with a light microscope. The subjects completed questionnaires to assess subjective symptoms and risk factors for dry eye disease (DED) and underwent general examinations for DED, including FBUT and cornea-conjunctival staining with fluorescein. Meibomian gland function was also investigated in lid margin findings, vascularity and mucocutaneous junction movement, lid irregularity, plugging, pouting, and meibum secretion grade scores.

Results:

Demodex mites were found in 20.6% (13/63) of the volunteers. Lid margin vascularity and meibum grades in the upper eyelid margins were significantly associated with the presence of Demodex mites. However, there were no significant differences in the diagnosis of meibomian gland dysfunction, FBUT, or ocular surface discomfort between the subjects with or without Demodex mites.

Conclusions:

Demodex mites are not rare in the cilia of a Japanese population. Lid margin vascularity and lower meibum quality may be associated with the presence of Demodex mites.
Association Between Dyslipidemia and Dry Eye Syndrome Among the Korean Middle-Aged Population
Authors: Choi Hye Rin , Lee Jung Hyun , Lee Hyung Keun , Song Jong Suk , Kim Hyeon Chang
Published: September 2019

Purpose:

Dry eye syndrome (DES) is a common eye disease caused by tear deficiency or excessive tear evaporation. Because the tear film layers play a major role in the pathogenesis of the evaporative dry eye, some previous articles have suggested the possible mechanism of dyslipidemia and DES. However, the previous results were inconsistent and few studies were conducted to find the independent relationship between dyslipidemia and DES. Therefore, we investigated the association of dyslipidemia with DES in middle-aged Korean adults.

Methods:

This study was conducted on 2272 participants (854 men and 1418 women) enrolled in the Study Group for Environmental Eye Disease (2013–2017) after excluding people who have taken lipid-lowering medication. Participants with total cholesterol ≥240 mg/dL or high-density lipoprotein cholesterol <40 mg/dL or low-density lipoprotein cholesterol ≥160 mg/dL or triglycerides ≥200 mg/dL are defined as having dyslipidemia. Using the ocular surface disease index, we measured the DES severity and defined DES as an ocular surface disease index score ≥13.

Results:

Men with dyslipidemia had an odds ratio of 1.29 (95% confidence interval, 0.97–1.71) for DES in an unadjusted model compared with those without DES. After adjusting for age, body mass index, hypertension, diabetes, occupations, smoking and drinking status, exercise, contact lens use, computer use, study cohorts, and calendar year of examinations, the adjusted odds ratio for DES was 1.40 (1.03–1.90) in men. However, there was no significant association between dyslipidemia and DES in women, even after stratifying by menopausal status.

Conclusions:

Our findings suggest that dyslipidemia may be associated with the prevalence of DES in Korean men, but not in women.
Expression of Lubricin in the Human Amniotic Membrane
Authors: Wang Jingyi , Chen Di , Sullivan David A. , Xie Huatao , Li Ying , Liu Yang
Published: September 2019

Purpose:

Lubricin, a boundary lubricant, is the body's unique antiadhesive, antifibrotic, antifriction, and antiinflammatory glycoprotein. This amphiphile is produced by numerous tissues and acts to regulate a number of processes, such as homeostasis, shear stress, tissue development, innate immunity, inflammation, and wound healing. We hypothesize that lubricin is also synthesized and expressed by the amniotic membrane (AM), which also possesses antiadhesive, antifibrotic, and antiinflammatory properties. We also hypothesize that lubricin, at least in part, mediates these AM capabilities. Our goal was to test our hypothesis.

Methods:

We obtained multiple samples of fresh, cryopreserved (CP), and freeze-dried (FD) human AMs, as well as fresh placental tissue as positive controls, and processed them for light microscopy, immunofluorescence, and western blot analyses. We also evaluated the ability of recombinant human lubricin to associate with FD-AMs.

Results:

Our results demonstrate that all fresh placental, fresh AM, and CP-AM samples contained lubricin. Lubricin was expressed in placental chorionic villi, AM epithelial and stromal cells, and CP-AM epithelia. No lubricin could be detected in FD-AMs but could be restored in FD-AMs after overnight incubation with recombinant human lubricin.

Conclusions:

This study supports our hypothesis that lubricin is expressed in human AMs. In addition, our data show that preservation methods influence the extent of this expression. Indeed, the disappearance of lubricin in FD-AMs may explain why dried AM reportedly loses its antiinflammatory and antiscarring abilities. It is possible that lubricin may mediate, at least in part, many of the biological properties of AMs.
Intraocular Degradation of XEN45 Gel Stent 3 Years After its Implantation
Authors: Widder Randolf A. , Kühnrich Pia , Hild Matthias , Rennings Corinna , Szumniak Alexander , Rössler Gernot F.
Published: September 2019

Introduction:

We report a case of XEN45 Gel Stent removal 3 years after its implantation. The stent had degraded with a closed lumen, so a new stent was implanted.

Case Report:

A 63-year-old woman was scheduled for XEN45 Gel Stent implantation. Three years after the primary surgery and 2 years after a surgical revision, second revision surgery was required. The conjunctiva was opened, and the implanted XEN Gel Stent was stripped of the adhesive scar tissues. No aqueous humor flow was seen through the stent, and therefore, the stent was removed. The intrascleral and intracameral parts had degraded. The surface of the stent was irregular and cobbled. A part of the lumen in the middle of the stent had closed.

Discussion:

We detected changes in the stent after its removal during the surgical revision with conjunctival opening, which is our standard approach for failed XEN Gel Stents. Most surgeons advise needling of the stent in cases of failure. However, in cases of needling, changes in the stent might not have been detected. Thus, the number of patients with similar changes as this report might be higher than the publications suggest. No unique characteristics distinguished this patient from those who had a functional XEN Gel Stent. The stent, in this case, might have been of inferior quality as an exception, or all stents might degrade over time. Therefore, gonioscopy should be performed carefully to detect any changes in the stent. In cases of suspected stent degradation, we recommend a revision surgery with conjunctival opening and removal of the stent in cases of degradation.
Evaluation of treatment results and prognostic factors of uterine sarcoma: A single-center experience
Authors: Momtahan Mozhdeh , Emami Fatemeh , Sari Aslani Fatemeh , Akbarzadeh-Jahromi Mojgan
Published: September 2019

Background:

Uterine sarcomas (US) constitute a rare heterogeneous group of gynecological malignancies with aggressive characteristics and poor prognosis. Identifying the histopathological factors that determine the prognosis of the tumor and efficacy of various treatment modalities provides a reliable source for efficient treatment of affected patients. This study presents our 11-year experience with US in the south of Iran.

Methods:

Medical records of 42 patients (2001-2012) with endometrial stromal sarcoma (ESS), leiomyosarcoma (LMS), and malignant mixed Müllerian tumor (MMMT) were investigated. Hazard ratio (HR) and 2- and 5-year survival of patients were analyzed based on the patients’ age, histopathological characteristics (tumor type, stage, necrosis, and mitotic index), and treatment modalities.

Results:

Twenty-four patients survived with median follow-up of 42.5 months; 18 died within 17 months, and 52.4% had recurrence, of whom 12 died. Two- and five-year survival rate was 78.6% and 61.9%, respectively, longest for ESS and shortest for MMMT. Higher age, tumor stage, necrosis, and mitotic index increased the HR of mortality. Radiotherapy resulted in a better survival, compared with chemotherapy alone or combined with radiotherapy.

Conclusion:

Although ESS had the best prognosis, MMMT was the most aggressive tumor with the shortest survival time. Histological type of the tumor, staging, tumor necrosis, and mitotic index had prognostic roles. Adjuvant radiotherapy resulted in a better survival, compared with surgery alone in early stage.
Effects of dangguijakyaksan on lower-extremity blood circulation disturbances in climacteric and postmenopausal women
Authors: Ahn Soo-Yeon , Baek Seon-Eun , Park Eun Ji , Kim Hye-Won , Ryuk Jin-Ah , Yoo Jeong-Eun
Published: September 2019

Background:

Climacteric women experience various disorders, including hot flush, depression, insomnia, arthralgia, and hand and foot numbness. Dangguijakyaksan is among the most common treatments for climacteric syndrome, and its effect on depression, insomnia, hot flush and quality of life (QOL) in climacteric women has been reported multiple times. A recent animal study found dangguijakyaksan decreased serum lipid factors and improved blood circulation in a menopausal rat model; however, these effects have not been assessed in clinical trials. This study aims to assess the clinical effects and safety of dangguijakyaksan for lower-extremity blood circulation disturbances in climacteric women.

Methods:

This is a single-center, randomized, double-blinded, placebo-controlled pilot study that will be conducted at Dunsan Korean Medicine Hospital at Daejeon University. Forty-six climacteric women with lower-extremity blood circulation disturbances will be recruited and randomized (1:1) into either the dangguijakyaksan or placebo group. After 8 weeks of administration, the effects and safety of dangguijakyaksan will be assessed.

The primary outcome is the visual analogue scale for lower-extremity blood circulation disturbances, and it will be assessed on visits 1, 2, and 3. The secondary outcomes, Kupperman's index and blood deficiency scoring system, will be assessed on visits 1, 2, and 3, and accelerated photoplethysmography and digital infrared thermal imaging will be performed on visits 1 and 3. Moreover, blood lipid profile, follicle-stimulating hormone, and estradiol levels will be measured at the screening visit and visit 3. Blood tests will be performed at the screening visit and visit 3 to assess the safety of dangguijakyaksan. Statistical analysis will be performed using R-3.3.3 (Another Canoe), and within-group study variable differences after drug administration will be analyzed using paired t-test or Wilcoxon signed-rank test.

Discussion:

We expect to confirm the effects and safety of dangguijakyaksan on lower-extremity blood circulation disturbances in menopause, which would provide foundational data for planning subsequent studies.
Breast lesion size assessment in mastectomy specimens
Authors: Wienbeck Susanne , Uhlig Johannes , Fischer Uwe , Hellriegel Martin , von Fintel Eva , Kulenkampff Dietrich , Surov Alexey , Lotz Joachim , Perske Christina
Published: September 2019

To compare the accuracy of breast lesion size measurement of cone-beam breast-CT (CBBCT), digital breast tomosynthesis (DBT) and full-field digital mammography (FFDM).

Patients scheduled for mastectomy due to at least 1 malignant breast lesion were included. Mastectomy specimens were examined by CBBCT, DBT, FFDM, and histopathology.

A total of 94 lesions (40 patients) were included. Histopathological analyses revealed 47 malignant, 6 high-risk, and 41 benign lesions. Mean histopathological lesion size was 20.8 mm (range 2–100). Mean absolute size deviation from histopathology was largest for FFDM (5.3 ± 6.7 mm) and smallest for CBBCT 50 mA, high-resolution mode (4.3 ± 6.7 mm). Differences between imaging modalities did not reach statistical significance (P = .85).

All imaging methods tend to overestimate breast lesion size compared to histopathological gold standard. No significant differences were found regarding size measurements, although in tendency CBBCT showed better lesion detection and cT classification over FFDM.
Characteristics of carcinogenic HPV genotypes in North China Plain and the association with cervical lesions
Authors: Liu Lihua , Wang Dexue , Dong Haixin , Jin Chengqiang , Jiang Liqing , Song Hui , Jin Chao , Wang Tong , Shi Cuiming , Yang Linqing , Wang Yunfei
Published: September 2019

Human papillomavirus (HPV) infection is a crucial health problem and caused substantial malignancy diseases among female worldwide. We aim to investigate the distribution of HPV subtype and the status of cervical cancer and precancerous lesions caused by HPV infection in North China Plain population. A total of 61,870 samples of outpatients and inpatients from January 2015 to May 2017 at the Affiliated Hospital of Jining Medical University were collected. All of the samples were tested by rapid flow-through hybridization HPV genotyping. Approximately 17,280 of the cases tested positive for HPV, indicating an infection rate of 27.9%. Approximately 7009 cases were compared to the results of cytological diagnosis. The top five HPV genotypes were HPV-16 (4.5%), HPV-52 (2.9%), HPV-58 (2.8%), HPV-53 (1.9%), and HPV-81 (1.9%). The youngest age group (age < 20 years) showed the highest infection rate (59.9%), and then decreased with age. As the degree of cervical lesions worsened gradually, the rate of high-risk HPV infection increased, such as 24.3% (322/1324) in the Cervicitis, 31.30% (560/1785) in the CINI, 54.1% (568/1050) in the CINII, 80.1% (693/865) in the CIN III, and 99.5% (428/430) in the cervical cancer group. These findings were significantly different from the 9.7% (155/1555) observed in the normal medical examination group (P < .05). This is the first study to demonstrate the characteristics of HPV and the association with cervical lesions in North China Plain population.
Survival rates following medical intensive care unit admission from 2003 to 2013
Authors: Kim Do Yeun , Lee Mi Hyun , Lee Sung Yeon , Yang Bo Ram , Kim Hyun Ah
Published: September 2019

The decision as to whether patients should be admitted to a medical intensive care unit (ICU), in the absence of information concerning survival rates or prognostic factors in survival, is often challenging. We analyzed survival trends in relation to hospital discharge and examined patient and hospital characteristics associated with survival following ICU care, using a sample of nationwide claims data in Korea from 2002 through 2013. The Korean government implements a compulsory social insurance program that covers the country's entire population, and the Korean National Health Insurance Service-National Sample Cohort (NHIS-NSC) data from 2002 based on this program were used for this study. The NHIS-NSC is a stratified random sample of 1,025,340 subjects selected from around 46 million Koreans. We evaluated annual survival trends using the Kaplan-Meier test. Analyses of the relationship between survival and patient and hospital characteristics were performed using Cox regression analyses. Employing a multivariate model, variables were selected using the forward selection method to consider the multicollinearity of variables. A total of 32,553 patients admitted to an ICU between 2002 and 2013 were identified among the eligible beneficiaries. The number of patients who had histories of ICU admission steadily increased throughout the study period, and patients older than 80 years constituted a progressively increasing proportion of ICU admissions, from 7.3% in 2002 to 16.9% in 2007 to 23.1% in 2013. The mean number of mechanical equipment items applied consistently increased, while no difference was observed in the trend for overall 1-year survival in patients following ICU treatment across the study period: the 1-year survival rate ranged from 66.7% (year 2003) to 64.2% (year 2010). Advanced age, cancer, renal failure, pneumonia, and influenza were all associated with heightened risk of mortality within 1 year. Our results should prove useful to older patients and their clinicians in their decisions regarding whether to seek ICU care, with the goals of improving the end-of life care and optimizing resource utilization.
Neointimal coverage after second generation drug-eluting stent implantation has a relationship with pre-existing atherosclerotic lesion characteristics
Authors: Nomoto Yohta , Nakagawa Masashi , Shirai Nobuyuki , Kajio Keiko , Mizutani Kazuki , Yamazaki Takanori , Sugioka Kenichi , Kamimori Kimio , Ueda Makiko , Izumiya Yasuhiro , Yoshiyama Minoru
Published: September 2019

The relationship between preexisting atherosclerotic lesion characteristics and neointimal thickness after second-generation drug-eluting stent (DES) placement is still unknown. Thus, we evaluated that relationship using optical coherence tomography (OCT).

A single-center, retrospective, observational study was conducted. Patients with stable angina or asymptomatic myocardial ischemia who received percutaneous coronary intervention for a de novo lesion using a second-generation DES under frequency domain OCT guidance and underwent follow-up coronary angiography (CAG) and OCT between December 2010 and December 2015 were included. The relationship between the neointimal thickness on the stent strut and the plaque characteristics was retrospectively evaluated using OCT immediately after stent implantation and at the time of follow-up CAG.

We analyzed 3459 struts from 20 stents in 15 patients. The mean follow-up period was 264 days. In the follow-up study, no angiographic in-stent restenosis was found. Of the 3459 struts, 3315 (95.8%) were covered with neointima. The median neointimal thicknesses of the stent struts on calcified, fibrous, and lipid-rich lesions were 20 μm (interquartile range [IQR], 10–50 μm), 70 μm (40–140 μm; P < .001), and 90 μm (50–170 μm; P < .001), respectively. These differences were observed regardless of the type of second-generation DES used.

Most of the stent struts were covered with neointima. The neointimal thickness after the second-generation DES implantation had a close relationship with the preexisting atherosclerotic lesion characteristics. In this study, we found differences in arterial healing processes due to underlying plaque; therefore, evaluating the lesion characteristics by OCT may predict the risk for future restenosis and thrombosis.
Clinical efficacy of weekly cisplatin for treatment of patients with breast cancer
Authors: Ma Ying , Zhang Nai-peng , An Ning , Li Wen-yuan , Zhao Wei , Liu Yan-cui
Published: September 2019

Background:

We will investigate the efficacy and safety of weekly cisplatin (WC) for treatment of patients with breast cancer (BC) systematically.

Methods:

This study will describe and critically appraise shared decision approaches used in randomized controlled trials of WC for treatment of patients with BC. We will comprehensively search the following databases: PubMed, EMBASE, Web of Science, Cochrane Library, CINAHL, PsycINFO, Allied and Complementary Medicine Database, Wanfang, and Chinese Biomedical Literature Database from inception through July 1, 2019. We will utilize RevMan V.5.3 software (London, UK) for statistical analysis.

Results:

This study will systematically explore the efficacy and safety of WC for the treatment of patients with BC through evaluating primary outcomes of overall survival, pathological complete response; and secondary outcomes of cancer-specific survival, recurrence-free survival, disease-free survival, quality of life, and toxicities.

Conclusion:

This study will provide latest evidence of WC for the treatment of patients with BC.

Systematic review registration:

PROSPERO CRD42019145358.
Burnout among doctors in China through 2018
Authors: Zheng Qin , Yang Kun , Wang Xue , Ou Zhenghang , Su Xiaopeng , Zhang Jing , Qu Miao
Published: September 2019

Background:

Burnout negatively impacts the mental and physical health doctors. More seriously, it leads to poor patient care. In China, the situation is severe and more efforts are needed to reveal the epidemiological characteristics of doctor burnout to develop improved strategies of alleviating it. Due to the large number of heterogeneous and sample size-restricted surveys currently published, meta-analysis and systematic reviews are critical to a thorough understanding of burnout among Chinese doctors.

Methods:

The Cochrane Collaboration criteria and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) will be followed to conduct and report the systematic review. We will conduct a comprehensive search on the data bases of China National Knowledge Infrastructure (CNKI), WanFang, PubMed, EMBASE, PsycINFO, and the Cochrane Library from their inception to December 2018. Prospective cohort and cross-sectional studies that described the prevalence of Chinese doctors’ prevalence will be eligible for inclusion. The risk of bias and methodological quality of the included studies will be assessed using a risk of bias tool and the Cochrane guidelines for observational studies. A generalized linear mixed model framework with the Poisson likelihood and the log link function will be used to access the incidence rate ratio. Multivariate Poisson regression framework will be conducted to adjust modeling heterogeneity and confounders, like difference regions and time periods. The risk of bias, heterogeneity, and quality of evidence will be assessed in accordance with the aforementioned guidelines.

Results:

The primary outcome will be the prevalence and distribution of 3 dimension of burnout in Chinese doctors, and the second will be the difference of prevalence between difference regions and time periods.

Discussion:

This systematic review and meta-analysis will help us to reveal the prevalence, characteristics, timeline, and correlation between these factors in burnout; we expect our work may provide a scientific basis for further prevention and intervention of burnout in Chinese doctors, eventually to improve the quality of health care.

PROSPERO registration number:

CRD42018104249.
Highly durable response to capecitabine in patient with metastatic estrogen receptor positive breast cancer
Authors: Barchiesi Giacomo , Krasniqi Eriseld , Barba Maddalena , Giulia Marina Della , Pizzuti Laura , Massimiani Gioia , Ciliberto Gennaro , Vici Patrizia
Published: September 2019

Rationale:

In estrogen receptor-positive HER2-negative (ER+HER2-) metastatic breast cancer, chemotherapy should be offered only to patients who develop endocrine resistance or have a rapid disease progression. However, the correct sequence of chemotherapy administration is still debated.

Patient concerns:

We report the case of a 49-year-old woman with ER+ HER2- metastatic breast cancer who experienced an exceptionally long response to capecitabine administered as second-line therapy following a first-line anthracycline-based chemotherapy.

Diagnoses:

The patient was diagnosed with ER+ HER2- metastatic breast cancer with massive liver involvement and mediastinal lymph nodes metastasis.

Interventions:

This patient was treated with capecitabine 1000 mg/mq bid given intermittently for 14 days within a 21-day cycle as a second-line therapy following a rapid progression on letrozole treatment given as a maintenance therapy.

Outcomes:

Our patient experienced a progression-free survival (PFS) >3 years with an exceptionally good quality of life (QoL).

Lessons:

In ER+HER2- metastatic breast cancer patients, capecitabine monochemotherapy in second line may be associated with a particularly satisfactory PFS and no impact in terms of QoL. Future studies focused on biomarkers with predictive ability may help select patients who represent the best candidates to this treatment.
Thoracic endovascular aortic repair in penetrating aortic ulcer combined with isolated left vertebral artery
Authors: Fan Weijian , Li Chuanyong , Zheng Guangfeng , Pan Zhichang , Rong Jianjie
Published: September 2019

Rationale:

Penetrating aorta ulcer (PAU) with isolated left vertebral artery (ILVA) is a rare condition, accounting for no more than 1% of all kinds of aorta diseases. And traditional treatment was open surgery with total arch replacement by elephant trunk. Here, we report a case of PAU combined with ILVA managed by thoracic endovascular aortic repair (TEVAR) technique.

Patient concerns:

A 65-year-old male with chronic hypertension and Nicotine abuse underwent intermittent back pain for 2 years and aggravated a bit for 1 week.

Diagnoses:

Preoperative computed tomography angiogram (CTA) indicated PAU combined with ILVA.

Interventions:

TEVAR was performed for PAU following with retrograde in situ fenestration and chimney technique for revascularization of ILVA and left subclavian artery (LSA), respectively.

Outcomes:

The operation was successfully and the patient was discharged from hospital after 1 week of treatment. Postoperatively, the images of CTA illustrated the patency of aorta, ILVA, and LSA without obvious endoleak. Besides, no ischemia attack or other relative syndromes were detected at 6-months follow-up.

Lessons:

This case demonstrates that TEVAR is an alternative to elephant trunk especially for PAU with ILVA. And it also showed the precise exposure of ILVA and necessity to reconstruct ILVA during TEVAR operation in order to reduce the occurrence of ischemia attack.
A novel scoring system predicting survival benefits of palliative primary tumor resection for patients with unresectable metastatic colorectal cancer
Authors: Cao Gaoyang , Zhou Wei , Chen Engeng , Wang Fei , Chen Li , Chen Min , Zhao Wei , Xu Jianbin , Zhang Wei , Zhang Guolin , Huang Xuefeng , Song Zhangfa
Published: September 2019

The role of palliative primary tumor resection (PPTR) in improving survival in patients with synchronous unresectable metastatic colorectal cancer (mCRC) is controversial. In this study, we aimed to evaluate whether our novel scoring system could predict survival benefits of PPTR in mCRC patients.

In this retrospective cohort study consecutive patients with synchronous mCRC and unresectable metastases admitted to Sir Run Run Shaw Hospital between January 2005 and December 2013 were identified. A scoring system was established by the serum levels of carcinoembryonic antigen (CEA), cancer antigen 19-9 (CA19-9), neutrophil/lymphocyte ratio (NLR), and lactate dehydrogenase (LDH). Patients with scores of 0, 1–2, or 3–4 were considered as being in the low, intermediate, and high score group, respectively. Primary outcome was overall survival (OS).

A total of 138 eligible patients were included in the analysis, of whom 103 patients had undergone PPTR and 35 had not. The median OS of the PPTR group was better than that of the Non-PPTR group, with 26.2 and 18.9 months, respectively (P < .01). However, the subgroup of PPTR with a high score (3–4) showed no OS benefit (13.3 months) compared with that of the Non-PPTR group (18.9 months, P = .11). The subgroup of PPTR with a low score (52.1 months) or intermediate score (26.2 months) had better OS than that of the Non-PPTR group (P < .001, P = .017, respectively).

A novel scoring system composed of CEA, CA19-9, NLR, and LDH values is a feasible method to evaluate whether mCRC patients would benefit from PPTR. It might guide clinical decision making in selecting patients with unresectable mCRC for primary tumor resection.
“Implementation Is so Difficult”
Authors: Floyd Nicole , Peterson Kimberly , Christensen Vivian , Anderson Johanna
Published: September 2019

Background:

Evidence use within learning health care systems can improve patient health outcomes. Embedded in the Veterans Health Administration (VHA) since 2007, the Veterans Affairs Evidence Synthesis Program (ESP) provides tailored evidence synthesis services to support VHA’s learning health care system goals. As part of the ESP’s ongoing quality improvement efforts, we have been surveying our users since 2016.

Methods:

We reviewed data from a survey of end-users received between September 5, 2016, and June 10, 2019. The survey assessed: (1) nature of decision-making needs; (2) actions resulting from the report’s findings; (3) implementation timeframe; and (4) overall perception of report content.

Results:

Feedback was received from 66 of the 138 operational partners requesting ESP products during the fiscal year 2015 through 2018. Requests commonly informed clinical guidance (58%), identified future research needs (58%), and determined VHA-specific implementation strategy (47%). A total of 91% of responders used reports, typically within 3 months after completion (82%). Use was typically for VHA publications and/or presentations to inform VHA policy or guidance (26%), to inform intervention/strategy adoption decisions (23%) and for medical device and therapy procurement decisions (21%). Over half (53%) of respondents indicated that it would be useful for ESP reports to include more guidance on implementing findings.

Conclusion:

Our survey of learning health system decision-makers’ actual patterns and timing of evidence use provides valuable new information that can further support development of other health system and evidence producer partnerships and identifies key needs for better supporting health systems’ uptake of evidence.
Differences in itch and pain behaviors accompanying the irritant and allergic contact dermatitis produced by a contact allergen in mice
Authors: Zhang Zhe , Malewicz Nathalie M. , Xu Xiaoyun , Pan Jianhao , Kumowski Nina , Zhu Tao , Shimada Steven G. , Nie Hong , LaMotte Robert H.
Published: September 2019

Introduction:

Irritant contact dermatitis (ICD) and allergic contact dermatitis (ACD) are inflammatory skin diseases accompanied by itch and pain. Irritant contact dermatitis is caused by chemical irritants eliciting an innate immune response, whereas ACD is induced by haptens additionally activating an adaptive immune response: After initial exposure (sensitization) to the hapten, a subsequent challenge can lead to a delayed-type hypersensitivity reaction. But, the sensory and inflammatory effects of sensitization (ICD) vs challenge of ACD are insufficiently studied. Therefore, we compared itch- and pain-like behaviors and inflammatory reactions evoked in mice during the sensitization (ICD) vs challenge phase (ACD) of application of the hapten, squaric acid dibutylester (SADBE).

Objectives:

Our aim was to compare itch- and pain-like behaviors and inflammatory reactions evoked in mice during the sensitization (ICD) vs challenge phase (ACD) of application of the hapten, squaric acid dibutylester (SADBE).

Methods:

Mice were sensitized on the abdomen with 1% SADBE (ACD) or vehicle treated (ICD, control). Spontaneous and stimulus-evoked itch- and pain-like behaviors were recorded in mice before and after 3 daily challenges of the cheek with 1% SADBE (ACD, ICD). Cutaneous inflammation was evaluated with clinical scoring, ultrasound imaging, skin thickness, histology, and analyses of selected biomarkers for contact dermatitis, IL-1β, TNF-α, CXCL10, and CXCR3.

Results:

Allergic contact dermatitis vs ICD mice exhibited more spontaneous site-directed scratching (itch) and wiping (pain). Allergic contact dermatitis—but not ICD—mice exhibited allodynia and hyperalgesia to mechanical and heat stimuli. Inflammatory mediators IL-1β and TNF-α were upregulated in both groups as well as the chemokine receptor, CXCR3. CXCL10, a CXCR3 ligand, was upregulated only for ACD. Inflammatory responses were more pronounced in ACD than ICD.

Conclusion:

These findings provide new information for differentiating the behavioral and inflammatory reactions to hapten-induced ICD and ACD.
Isolation and quantification of blood apoptotic bodies in neurological patients
Authors: Serrano-Heras Gemma , Díaz-Maroto Inmaculada , Carrión Blanca , Perona-Moratalla Ana B. , Gracia Julia , Arteaga Sandra , Hernández-Fernández Francisco , García-García Jorge , Castro-Robles Beatriz , Ayo-Martín Oscar , Segura Tomás
Published: September 2019

Dysregulation of apoptosis may contribute to the etiology and/or progression of several prevalent diseases, including stroke and neurodegenerative pathologies. So, detection of the apoptotic processes in patients would be useful in daily clinical practice, However, thein vivoanalysis of apoptosis that occurs in tissue has limitations. We therefore propose to use circulating apoptotic bodies as biomarkers for measuring apoptotic death in patients. Since there is no scientific literature establishing the most appropriate method for measuring apoptotic bodies from human blood samples, we here describe a reproducible centrifugation-based method combined with electron microscopy, dynamic light scattering and flow cytometry studies to isolate, characterize and quantify plasma apoptotic bodies of patients with ischemic stroke, multiple sclerosis and Parkinson’s disease. The analysis revealed that our isolation protocol achieves notable recovery rates of highly-purified intact apoptotic bodies. This easy and rapid procedure would help physicians to implement the use of plasma apoptotic bodies analysis as a non-invasive tool to monitor apoptotic death in neurological patients for prognostic purposes and for following disease activity and assessing drug effectiveness.
PINK1-dependent phosphorylation of Serine111 within the SF3 motif of Rab GTPases impairs effector interactions and LRRK2 mediated phosphorylation at Threonine72
Authors: Vieweg Sophie , Mulholland Katie , Bräuning Bastian , Kachariya Nitin , Lai Yu-Chiang , Toth Rachel , Sattler Michael , Groll Michael , Itzen Aymelt , Muqit Miratul M. K.
Published: September 2019

Loss of function mutations in the PINK1 kinase are causal for autosomal recessive Parkinson disease (PD) whilst gain of function mutations in the LRRK2 kinase cause autosomal dominant PD. PINK1 indirectly regulates the phosphorylation of a subset of Rab GTPases at a conserved Serine111 (Ser111) residue within the SF3 motif. Using genetic code expansion technologies we have produced stoichiometric Ser111-phosphorylated Rab8A revealing impaired interactions with its cognate guanine nucleotide exchange factor (GEF) and GTPase activating protein (GAP). In a screen for Rab8A kinases we identify TAK1 and MST3 kinases that can efficiently phosphorylate the Switch II residue Threonine72 (Thr72) in a similar manner as LRRK2. Strikingly we demonstrate that Ser111 phosphorylation negatively regulates the ability of LRRK2 but not MST3 or TAK1 to phosphorylate Thr72 in vitro and demonstrate an interplay of PINK1- and LRRK2-mediated phosphorylation of Rab8A in cells. Finally, we present the crystal structure of Ser111-phosphorylated Rab8A and NMR structure of Ser111-phosphorylated Rab1B that does not demonstrate any major changes suggesting that the phosphorylated SF3 motif may disrupt effector-Switch II interactions. Overall, we demonstrate antagonistic regulation between PINK1-dependent Ser111 phosphorylation and LRRK2-mediated Thr72 phosphorylation of Rab8A suggesting that small molecule activators of PINK1 may have therapeutic potential in patients harbouring LRRK2 mutations.
Dynamic rewiring of the human interactome by interferon signalling
Authors: Kerr Craig H. , Skinnider Michael A. , Madero Angel M. , Andrews Daniel D.T. , Stacey R. Greg , Chan Queenie W.T. , Stoynov Nikolay , Jan Eric , Foster Leonard J.
Published: September 2019

Background

The type I interferon (IFN) response is an ancient pathway that protects cells against viral pathogens by inducing the transcription of hundreds of IFN-stimulated genes (ISGs). Transcriptomic and biochemical approaches have established comprehensive catalogues of ISGs across species and cell types, but their antiviral mechanisms remain incompletely characterized. Here, we apply a combination of quantitative proteomic approaches to delineate the effects of IFN signalling on the human proteome, culminating in the use of protein correlation profiling to map IFN-induced rearrangements in the human protein-protein interaction network.

Results

We identified >27,000 protein interactions in IFN-stimulated and unstimulated cells, many of which involve proteins associated with human disease and are observed exclusively within the IFN-stimulated network. Differential network analysis reveals interaction rewiring across a surprisingly broad spectrum of cellular pathways in the antiviral response. We identify IFN-dependent protein-protein interactions mediating novel regulatory mechanisms at the transcriptional and translational levels, with one such interaction modulating the transcriptional activity of STAT1. Moreover, we reveal IFN-dependent changes in ribosomal composition that act to buffer ISG protein synthesis.

Conclusions

Our map of the IFN interactome provides a global view of the complex cellular networks activated during the antiviral response, placing ISGs in a functional context, and serves as a framework to understand how these networks are dysregulated in autoimmune or inflammatory disease.
Spatial control of nucleoporin assembly by Fragile X-related proteins
Authors: Agote-Arán Arantxa , Schmucker Stephane , Jerabkova Katerina , Boyer Inès Jmel , Berto Alessandro , Pacini Laura , Ronchi Paolo , Kleiss Charlotte , Guerard Laurent , Schwab Yannick , Moine Hervé , Mandel Jean-Louis , Jacquemont Sebastien , Bagni Claudia , Sumara Izabela
Published: September 2019

Nucleoporins (Nups) build highly organized Nuclear Pore Complexes (NPCs) at the nuclear envelope (NE). Several Nups assemble into a sieve-like hydrogel within the central channel of the NPCs to regulate nucleocytoplasmic exchange. In the cytoplasm, a large excess of soluble Nups has been reported, but how their assembly is restricted to the NE is currently unknown. Here we show that Fragile X-related protein 1 (FXR1) can interact with several Nups and facilitate their localization to the NE during interphase through a microtubule and dynein-dependent mechanism. Downregulation of FXR1 or closely related orthologs FXR2 and Fragile X mental retardation protein (FMRP) leads to the accumulation of cytoplasmic Nup protein condensates. Likewise, several models of Fragile X syndrome (FXS), characterized by a loss of FMRP, also accumulate cytoplasmic Nup aggregates. These aggregate-containing cells display aberrant nuclear morphology and a delay in G1 cell cycle progression. Our results reveal an unexpected role for the FXR protein family and dynein in the spatial regulation of nucleoporin assembly.

Highlights

Cytoplasmic nucleoporins are assembled by Fragile X-related (FXR) proteins and dynein

FXR-Dynein pathway downregulation induces aberrant cytoplasmic aggregation of nucleoporins

Cellular models of Fragile X syndrome accumulate aberrant cytoplasmic nucleoporin aggregates.

FXR-Dynein pathway regulates nuclear morphology and G1 cell cycle progression

eTOC Blurb

Nucleoporins (Nups) form Nuclear Pore Complexes (NPCs) at the nuclear envelope. Agote-Arán at al. show how cells inhibit aberrant assembly of Nups in the cytoplasm and identify Fragile X-related (FXR) proteins and dynein that facilitate localization of Nups to the nuclear envelope and control G1 cell cycle progression.

Graphical abstract
GRASP: a Bayesian network structure learning method using adaptive sequential Monte Carlo
Authors: Yu Kaixian , Cui Zihan , Qiu Xing , Zhang Jinfeng
Published: September 2019

Bayesian networks (BNs) provide a probabilistic, graphical framework for modeling high-dimensional joint distributions with complex dependence structures. BNs can be used to infer complex biological networks using heterogeneous data from different sources with missing values. Despite extensive studies in the past, network structure learning from data is still a challenging open question in BN research. In this study, we present a sequential Monte Carlo (SMC) based three-stage approach, GRowth-based Approach with Staged Pruning (GRASP). A double filtering strategy was first used for discovering the overall skeleton of the target BN. To search for the optimal network structures we designed an adaptive SMC (adSMC) algorithm to increase the diversity of sampled networks which were further improved by a new stage to reclaim edges missed in the skeleton discovery step. GRASP gave very satisfactory results when tested on benchmark networks. Finally, BN structure learning using multiple types of genomics data illustrates GRASP’s potential in discovering novel biological relationships in integrative genomic studies.