bluuebunny/crossref_metadata_2025 huggingface dataset:
Staplers or clips?
Authors: Liu Yu , Huang Zhongli , Chen Yuntian , Liao Banghua , Luo Deyi , Gao Xiaoshuai , Wang Kunjie , Li Hong
Published: November 2018

Background:

Controlling of the renal vessels is a critical step in live donor nephrectomy (LDN). Currently, mainly 2 devices, Hem-o-Lok clips and staplers, are utilized to control vessels during LDN. Both of them have advantages and disadvantages.

Methods:

This systematic review and meta-analysis was aimed to compare the safety and the efficacy of the 2 devices and to identify the better one in LDN. A systematic search for related publications in the databases of PubMed, Medline, Embase, the Cochrane Library, and Web of Science through February 2018 was performed. Eight studies were selected and evaluated with the Newcastle-Ottawa Scale (NOS).

Results:

The meta-analysis result showed that utilization of Hem-o-Lok clips resulted in greater amount of estimated blood loss (mean differences [MD]: 40.10; 95% confidence interval [CI] 4.37–75.84) and longer time of warm ischemia (WIT) (MD: 55.61; 95% CI 36.79–74.43) than using staplers. Residual vascular length of grafts in clip group was longer than that in stapler group (MD: 2.51; 95% CI 0.78–4.24). However, the differences in primary outcomes such as device failure rate, death rate, and severe hemorrhage rate, were not significant between these 2 groups. In addition, utilization of Hem-o-Lok clips costed approximate $400 lower than staplers per patient.

Conclusion:

This study revealed that Hem-o-Lok clips and staplers have the similar function in LDN renal ligation, regarding the device failure rate, death rate, and severe hemorrhage rate. However, the surgeons would benefit from the clips in terms of the residue length of vessels, these outstanding features provide operation convenience and flexibility, such as right-sided donor nephrectomies, early vascular bifurcation, and rare vascular variation. In addition, the clips have potential economic advantages. In some developing countries, it would reduce the healthcare expenditure.
Vertigo caused by longus colli tendonitis
Authors: Shen Yifeng , Zhou Qiaoyin , Zhu Xinyue , Qiu Zuyun , Jia Yan , Liu Zixiang , Li Shiliang
Published: November 2018

Rationale:

Tendinitis of the longus colli muscle is an aseptic inflammatory process leading to acute posterior neck pain, neck stiffness, and dysphagia or odynophagia. We present a patient exhibiting an infrequent symptom, vertigo. This is the first description of the occurrence of vertigo symptoms caused by longus colli tendinitis.

Patient concerns:

A 38-year-old man was diagnosed with vertigo, presenting with a 1-month history of dizziness, palpitations, and numbness in the hands.

Diagnosis:

Longus colli tendinitis. The diagnosis was established using magnetic resonance imaging fat-suppression sequences.

Interventions:

Treatment with corticosteroid injections and acupotomy.

Outcomes:

The symptoms relieved immediately after the treatment and complete resolution of the symptoms was observed after 1 week.

Lessons:

Longus colli tendinitis with vertigo is an under-reported condition in the literature and physicians should be aware of its existence. A lack of familiarity with the anatomy of the prevertebral space and its variable radiographic appearance makes the diagnosis of longus colli tendinitis clinically difficult. Misdiagnosis of this condition may lead to unnecessary interventions in vertigo.
3.0T Contrast-enhanced whole-heart coronary magnetic resonance angiography for simultaneous coronary artery angiography and myocardial viability in chronic myocardial infarction
Authors: Chen Zhiyong , Sun Bin , Duan Qing , Xue Yunjing , Chen Lianglong
Published: November 2018

To evaluate the accuracy of contrast-enhanced whole-heart magnetic resonance coronary angiography at 3.0T for assessing significant stenosis (≥50% lumen diameter reduction) in patients with myocardial infarction, by using conventional coronary artery angiography as the reference standard, and also test the performance of that for the detection and assessment of chronic myocardial infarction (MI), compared with standard delayed-enhancement coronary magnetic resonance (DE-CMR) for the determination of infarct size.

We studied 42 consecutive patients (37 men, 5 women, mean age 58.5 ± 10.7 years) with MI scheduled for conventional coronary angiography. Contrast-enhanced whole-heart coronary magnetic resonance angiography (CMRA) was employed after sublingual nitroglycerin (NTG) with the abdominal banding rolled tightly along the side of ribs. Finally, a 3D phase-sensitive inversion-recovery gradient-echo (3D-PSIR-GRE) sequence was performed during free breathing. The assessment of MI sizes on WH-CMRA reconstructed images and 3D-PSIR-GRE images were compared using a paired student t test.

The acquisition of CMRA was completed in 40 (95.2%) of 42 patients, with an imaging time averaged at 9.5 ± 3.1 minutes. The average navigator efficiency was 47%. The sensitivity, specificity, and positive and negative predictive values of whole-heart CMRA for the detection of significant lesions on a segment-by-segment analysis were 91.7% (95% confidence interval [CI] 83.8–96.1), 84.0% (95% CI 80.0–87.4), 57.9% (95% CI 50.0–65.8), 97.7% (95% CI 95.3–98.9), respectively, and on a patient-based analysis 93.5% (95% CI 77.2–98.9), 88.9% (95% CI 50.7–99.4), 96.7% (95% CI 80.9–99.8), and 80.0% (95% CI 44.2–96.5), respectively. Infarcts were generally higher on the CE-CMRA technique compared with the standard technique (18.0 ± 7.2 cm3 vs 16.1 ± 6.4 cm3; P < .0001).

Contrast-enhanced whole-heart CMRA with 3.0-T not only may permit reliable detection of significant obstructive coronary artery disease in patients with myocardial infarction, but also could identify and quantify the volume of myocardial infarction. This technique could be considered the preferred approach in patients who could not overcome longer scanning times or unable to hold their breath instead of delayed-enhancement magnetic resonance imaging for detection of infarcted myocardium. However, compared with standard imaging, the volume of myocardial infarction is slightly overestimated.
A novel subchondral bone-grafting procedure for the treatment of giant-cell tumor around the knee
Authors: Wu Minhao , Yao Shiyi , Xie Yuanlong , Yan Feifei , Deng Zhouming , Lei Jun , Cai Lin
Published: November 2018

The vast majority of giant-cell tumors occur around the knee and characteristically affect the subchondral bone. Thermal damage to the articular cartilage arising from the application of polymethylmethacrylate (PMMA) or extensive intralesional curettage presents a challenging problem to orthopedic surgeons and patients due to compliance issues. For this reason, we developed a new subchondral bone-grafting procedure to restore massive bone defects and reduce degenerative changes in the knee.

The aim of this study was to describe the novel subchondral bone-grafting procedure and evaluate clinical outcomes in patients with giant-cell tumors around the knee.

This retrospective single-center study included a total of 27 patients with giant-cell tumors in the distal femur and proximal tibia admitted to our department from January 2012 to December 2015 and treated with aggressive intralesional curettage. Eleven males and 16 females were included. All cases underwent subchondral autograft bone grafting followed by bone cement reconstruction and instrument internal fixation. The Musculoskeletal Tumor Society (MSTS) score and short form-36 (SF-36) were applied to assess the functional outcome of the knee joint and quality of life. Tumor recurrence, Kellgren and Lawrence (KL) grade, and the distance of the cement to the articular surface were assessed throughout the sample.

All cases were followed up after surgery for an average of 32.9 ± 7.1 months (range 25–57 months). At the end of the follow-up period, all patients were alive and free from pulmonary metastasis. Complications associated with this surgery occurred only in 1 patient (3.7%), who presented with an incision infection that resolved with regular dressing and antibiotics. No fractures, instrument breakage, or joint fluid leakage occurred. Local recurrence occurred in 1 case (3.7%) at the distal femur after 23 months and was treated by wide resection followed by prosthesis reconstruction. Twenty-four patients (89%) did not develop radiographic findings of osteoarthritis: at the final follow-up 2 patients (7.4%), had progressed to KL1 and 1 patient had progressed to KL2. According to the MSTS scoring system, the functional score of the affected knee joint at the last follow-up ranged from 80% to 97%, with an average of 87.3%. The quality of life parameters assessed by the SF-36 survey at the last follow-up ranged from 47 to 96, with an average of 77.

For patients with giant-cell tumor of bone near the knee, subchondral bone grafting combined with bone cement reconstruction is recommended as a feasible and effective treatment modality.
Role of preoperative endoscopic clipping in laparoscopic distal gastrectomy for early gastric cancer
Authors: Park Dae Hwa , Moon Hee Seok , Sul Ji Young , Kwon In Sun , Yun Gee Young , Lee Seo Hee , Park Jae Ho , Kim Ju Seok , Kang Sun Hyung , Lee Eaum Seok , Kim Seok Hyun , Sung Jae Kyu , Lee Byung Seok , Jeong Hyun Yong
Published: November 2018

In this study, we evaluate the usefulness of preoperative endoscopic clipping for early gastric cancer (EGC) localization in laparoscopic distal gastrectomy.

We retrospectively screened all consecutive patients who underwent laparoscopic distal gastrectomy for EGC by 1 surgeon at Chungnam National University Hospital between January 2014 and December 2016. Patients who underwent combined surgery and patients who had tumors at the lower third of the stomach were excluded. Endoscopic clipping was performed prior to surgery by specialized endoscopists. During the operation, endoscopic metal clips were found using surgical devices, and laparoscopic vessel clips were attached on the presumed site; thereafter, intraoperative radiographs were obtained for confirmation.

We analyzed a total of 196 patients; of them, 101 were classified into the clipping group (CG) and 95 into the non clipping group (NCG). The 2 groups were comparable regarding their demographic characteristics. The CG showed less additional resection (2 of 101 patients [2.0%] vs 9 of 95 patients [9.4%], P = .021) and better outcomes in terms of the operation time (P = .000), duration of hospital stay (P = .036), and postoperative atelectasis (P = .001) than the NCG.

Preoperative endoscopic clipping was helpful in determining the exact resection margin in laparoscopic distal gastrectomy for EGC.
Nivolumab therapy for metastatic collecting duct carcinoma after nephrectomy
Authors: Yasuoka Shotaro , Hamasaki Tsutomu , Kuribayashi Eigo , Nagasawa Masato , Kawaguchi Takanori , Nagashima Yoji , Kondo Yukihiro
Published: November 2018

Rationale:

Collecting duct carcinoma (CDC) is a rare type of nonclear renal cell carcinoma, often presenting at an advanced stage of the disease, and standard treatment guidelines have not been established.

Patient concerns:

A 73-year-old man was admitted to our hospital with complaints of fever and lower right back pain.

Diagnoses:

Computed tomography revealed a poorly defined tumor of the right kidney without metastasis. The patient underwent right radical nephrectomy and was diagnosed with clinical stage T1bN0M0 renal cancer; the pathological findings showed collecting duct carcinoma.

Interventions:

After nephrectomy, multiple lung metastases were found in the following month, so first-line chemotherapy of gemcitabine (1000 mg/m2 on days 1 and 8, every 21 days) and cisplatin (70 mg/m2 on day 2, every 21 days) was administered. Due to disease progression, targeted therapy with axitinib (10 mg/body) and second-line chemotherapy of paclitaxel (200 mg/m2 on day 1, every 21 days) and carboplatin (area under the curve of 6 on day 1, every 21 days) were subsequently administered. However, the lung metastases progressed and new metastases spread to the right adrenal gland, liver, and lymph nodes. Based on the high expression of programmed death-ligand 1 in tumor cells, we treated the patient with the immune checkpoint inhibitor nivolumab.

Outcomes:

After 2 courses of treatment, he experienced a partial response and improved performance status, and thus was discharged from the hospital. To date, the patient is on his fifth course of treatment as an outpatient without disease progression.

Lessons:

The findings of our study suggest that nivolumab may be effective even if the patient has highly progressive CDC with a low PS, if PD-L1 is highly expressed in the tumor cells.
The association between body mass index and the risk of different gastrointestinal cancers
Authors: Ma Xueni , Gao Ya , Li Jipin , Zhang Dekui , Tian Jinhui
Published: November 2018

Background:

Changes in our lifestyle over the past few decades have led to a significant increase in the worldwide prevalence of both overweight (defined as a body mass index [BMI]≥25 kg/m2) and obesity (BMI≥30 kg/m2), thus leading to numerous harmful consequences for an individual's health. Several meta-analyses support the link between obesity and different gastrointestinal cancers, but substantial heterogeneity exists between studies. We will synthesize published systematic reviews to evaluate the association between body mass index (BMI) and the incidence and mortality of different gastrointestinal cancers.

Methods:

PubMed, EMBASE, and the Cochrane Library will be systematically searched for systematic reviews, meta-analyses, and pooled analyses in July, 2018. Two review authors will independently screen titles and abstracts for relevance, assess full texts for inclusion, carry out data extraction, and appraise methodological quality using AMSTAR checklist and reporting quality using PRISMA statement. The association between BMI and different gastrointestinal cancers will be estimated by computing the pooled relative risk (RR) and its 95% confidence interval (CI), which will be calculated from the adjusted RR, odds ratio, or hazard ratio, and 95% CI offered in the studies. Heterogeneity between studies will be assessed with the I

2
statistic as a measure of the proportion of total variation in estimates that is due to heterogeneity, where I

2
values of 25%, 50%, and 75% correspond to cut-off points for low, moderate, and high degrees of heterogeneity. The random effects model will be used as the pooling method when significant heterogeneity existed and the fixed effect model will be used when no heterogeneity was observed. Possible publication bias will be tested by Begg and Egger test.

Discussion:

This overview of systematic reviews will provide an accessible, comprehensive synthesis with which to inform clinicians and the development of guidelines for the management of the individuals with high BMI.

Ethics and dissemination:

Only published secondary data will be used in this study, and therefore ethics approval is not required.

PROSPERO registration number: CRD42018107334.
Effects of Shuganjianpihuatanxingqi decoction on mild subclinical hypothyroidism
Authors: Bai Litao , Zhao Jing , Gao Jialiang , Li Fei , Wei Fan , Li Jun , Xiao Yao , Han Xu , Wang Yaoli , Wang Danwei , Wu Fangying , Wei Junping
Published: November 2018

Introduction:

Mild subclinical hypothyroidism (SCH) can cause depression, fatigue, cognitive dysfunction, or other hypothyroid symptoms, and even progress to hypothyroidism. The treatment of mild SCH is controversial. Shuganjianpihuatanxingqi decoction (SD) is a frequently prescribed Chinese herbal medicine in patients with mild SCH. However, scientific evidence is needed to confirm the therapeutic effect of SD.

Methods and analysis:

This study is a randomized, double-blind, and controlled clinical trial. A total of 228 participants with the diagnosis of mild SCH will be randomly assigned to the SD or placebo group in a ratio of 1:1. Participants will receive treatment for 12 weeks and undergo 12-month follow-up. The primary outcome measure is the thyroid-stimulating hormone level, and secondary outcomes will be the differences in the results of Thyroid-related Quality of Life Questionnaire, blood lipids, and Traditional Chinese Medicine Symptom Score Scale between baseline and at 12 weeks after intervention.

Ethics and dissemination:

The study has been approved by Guang’anmen Hospital of China Academy of Chinese Medical Sciences (no.2018-005-ky-01). The trial results will be published via peer-reviewed journals and the Clinical Research Information Service.

Trial registration number:

ChiCTR1800015781 (approval date: 20 April 2018).
A case report of metastatic breast cancer initially presenting with esophageal dysphagia
Authors: Liu Ailing , Feng Yunlu , Chen Bo , Li Li , Wu Dongsheng , Qian Jiaming , Yang Aiming
Published: November 2018

Rationale:

Breast cancer metastasis to the esophagus is uncommon. To our knowledge, the present case is the first report of breast cancer with dysphagia as the initial symptom.

Patient concerns:

A 62-year-old woman was admitted to our hospital for progressive dysphagia.

Diagnoses:

Endoscopic ultrasound-guided fine needle biopsy of the esophageal lesion found poorly differentiated carcinoma, and surgical resection of the breast nodule revealed invasive ductal carcinoma.

Interventions:

The patient underwent an esophagectomy, and the immunohistochemistry of surgical specimen was identified as metastatic breast cancer. Then patient was treated with chemotherapy and hormone therapy.

Outcomes:

The patient remained symptom-free during 5 months of follow-up examinations.

Lessons:

This case indicates that metastatic breast cancer to the esophagus should be considered as a cause of esophageal stricture in older women.
Massive idiopathic spontaneous hemothorax complicating anti-N-methyl-d-aspartate receptor encephalitis
Authors: Wang Xin , Lai Yutian , Li Pengfei , Zhou Kun , Che Guowei
Published: November 2018

Rationale:

Spontaneous hemothorax is a subcategory of hemothorax which can be life threatening. The etiology of spontaneous hemothorax can be various, and in some rare cases the causes remained unknown. Hence, it is quite difficult to establish the diagnosis. Here, we report a case of spontaneous hemothorax in a young female patient who was recently diagnosed with anti-N-methyl-d-aspartate receptor encephalitis (anti-NMDAR encephalitis).

Patient concerns:

A 20-year-old female was transferred to emergency department of our hospital from local hospital presented with insomnia, mood lability, tonic-clonic seizure, and decreased level of consciousness.

Diagnoses:

The diagnosis of anti-NMDAR encephalitis was established by detection of cerebrospinal fluid (CSF) and serum antibodies to the NMDA receptor. During the hospital stay, the patient developed massive spontaneous hemothorax and was confirmed by closed-tube thoracostomy.

Interventions and outcomes:

Video-assisted thoracotomy was performed to evacuate the blood clots and also to obtain pleural biopsy specimen for diagnostic evaluation. However, the reason of hemothorax remained idiopathic. The postoperative status of this patient was uneventful, and she was discharged on postoperative day 45 as her mental status improved markedly.

Lessons:

In this case, the patient had both anti- NMDAR encephalitis and autoimmune thyroid disease. Based on it, we suspected that the patient subjected to severe autoimmune response and inflammatory reaction, which might explain the pathologic changes of parietal pleura and visceral pleura. We recommend the suspicion of spontaneous hemothorax should be considered when the patients with autoimmune diseases present with hemorrhage-related signs or symptoms.
Okbyungpoongsan (Yupingfeng) for treating allergic rhinitis
Authors: Lee Minseong , Kim Youngjo , Lee Ju Ah
Published: November 2018

Background:

Okbyungpoongsan (OBPS) is widely used as a treatment for allergic rhinitis (AR) in Far East countries. Many clinical trials have assessed the efficacy and safety of the OBPS formula for treating AR. Here, we systematically will review the clinical evidence for and against administration of OBPS.

Methods and analysis:

All RCTs of decoctions or modified decoctions will be included. The methodological quality of the RCTs will be analyzed using the Cochrane Collaboration tool for assessing risk of bias, while confidence in the cumulative evidence will be evaluated using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) instrument.

Ethics and dissemination:

This systematic review will be published in a peer-reviewed journal and will also be disseminated electronically and in print. The review will be updated to provide additional information and guide healthcare practices.

Registration number: CRD42017080292.
Outcomes of Noninvasive Ventilation in Obese Patients With Acute Asthma Exacerbations
Authors: Thapamagar Suman B. , Doshi Viral , Shenoy Sundeep , Ganesh Aarthi , Lankala Shilpa
Published: November 2018

Background:

The role of noninvasive positive pressure ventilation (NIPPV) in acute asthma exacerbation is controversial. However, the outcome of NIPPV in obese patients with asthma during such exacerbation has not been well studied despite well-established relationship between obesity and asthma.

Study Question:

Does body mass index (BMI) play a role in the outcome of NIPPV during an acute exacerbation and does it predict of the success or failure of NIPPV?

Study Design:

The study was a retrospective analysis by design. The purpose of the study was to assess factors predicting the success or failure of NIPPV. The entire cohort was divided into 2 groups: patients who failed NIPPV and patients who did not. Univariate and multivariate regression analysis was used to predict the variables. Stepwise selection method was used to select variables for final regression model.

Results:

A total 96 patients were included in the study. Of those, 18 patients (18.9%) failed NIPPV and required endotracheal intubation (group 1). Rest (78.1%) did not fail NIPPV (group 2). Mean age of the study population was 48.8 years and 53% of patients were female. In the univariate analysis, the group that did not fail NIPPV (group 2) had significantly higher number of obese patients (47.9% versus 22.2%; P 0.013). Multivariate analysis showed significant association between BMI categories (BMI of 30 or more) and failure of NIPPV (odds ratio 0.26, 95% confidence interval, 0.08–0.85; P-value 0.017). Forced introduction of smoking status as a risk factor did not change the significance of association.

Conclusion:

Despite the limitations of the study design and the sample size, our analysis showed that patients with high BMI (obese) fared well with NIPPV during acute asthma exacerbation. Because there are controversies on use of NIPPV during asthma exacerbation, larger-scale prospective studies are needed to better understand the role of NIPPV in obese patients with asthma during acute exacerbation.
A Survey Assessing Pediatric Transport Team Composition and Training
Authors: Patel Meral M. , Hebbar Kiran B. , Dugan Mark C. , Petrillo Toni
Published: November 2018

Objective

The aim of this study was to assess national pediatric/neonatal specialty transport teams' composition and training requirements to determine if any current standardization exists.

Methods

This was a survey of the transport teams listed with the American Academy of Pediatrics via SurveyMonkey.

Results

While most of the teams maintain internal criteria for team competency and training, there is large variation across team compositions. The vast majority of the teams have a nurse-led team with the addition of another nurse, medic, and/or respiratory therapist regardless of mode of transport. Many of the teams report adjusting team composition based on acuity. Fewer than 15% of teams have a physician as a standard team member. More than 80% required a minimum number of supervised intubations prior to independent practice; however, the number varied largely from as little as 3 to as many as 30. Eighty-eight percent of the teams report using simulation as part of their education program, but again there were marked differences between teams as to how it was used.

Conclusions

There is tremendous variability nationally among pediatric/neonatal transport teams regarding training requirements, certifications, and team composition. The lack of standardization regarding team member qualifications or maintenance of competency among specialized transport teams should be looked at more closely, and evidence-based guidelines may help lead to further improved outcomes in the care of critically ill pediatric patients in the prehospital setting.
Implementing the 2016 American Academy of Pediatrics Guideline on Brief Resolved Unexplained Events
Authors: Brand Donald A. , Mock Ann , Cohn Elizabeth , Krilov Leonard R.
Published: November 2018

Objectives

A “brief resolved unexplained event” refers to sudden alterations in an infant's breathing, color, tone, or responsiveness that prompt the parent or caregiver to seek emergency medical care. A recently published clinical practice guideline encourages discharging many of these infants home from the emergency department if they have a benign presentation. The goal is to avoid aggressive inpatient investigations of uncertain benefit. The present research explored parents' reactions to the prospect of returning home with their infant following such an event.

Methods

The study used qualitative research methods to analyze semistructured, audio-recorded interviews of parents who had witnessed a brief resolved unexplained event between 2011 and 2015 and taken their infant to the emergency department of an academic teaching hospital.

Results

A total of 22 parent interviews were conducted. The infants included 8 boys and 14 girls aged 3.6 ± 3.5 months (mean ± SD). Qualitative analysis of interview transcripts revealed a near-universal apprehension about the child's well-being, ambivalence about the best course of action after the evaluation in the emergency department, and need for reassurance about the unlikelihood of a recurrence. Parents did not, however, answer the main research question with a single voice: attitudes toward the return-home scenario ranged from unthinkable to extreme relief. Two-thirds of parents expressed at least some reservations about the idea of returning home.

Conclusions

Successful implementation of the 2016 guideline will require close attention to the parent's point of view. Otherwise, parental resistance is likely to compromise clinicians' best efforts.
Socioeconomic Status and Analgesia Provision at Discharge Among Children With Long-Bone Fractures Requiring Emergency Care
Authors: Ortega Henry W. , Velden Heidi Vander , Truong Walter , Arms Joseph L.
Published: November 2018

Background

Inadequate treatment of painful conditions in children is a significant and complex problem. The objective of this study was to examine the effect of socioeconomic status on the provision of analgesic medicines at discharge in children treated emergently for a long-bone fracture.

Methods

A retrospective review of all patients during a 1-year period with a long-bone fracture treated in 2 urban pediatric emergency departments (EDs) was performed.

Results

Eight hundred seventy-three patients were identified who met our inclusion criteria. Sixty percent of patients received a prescription for an opioid-containing medicine, and 22% received a prescription for an over-the-counter analgesic medicine at ED discharge. Socioeconomic status had no effect on opioid analgesic prescriptions at discharge. Patients in the lowest-income group were younger, presented to the ED longer after an injury, were likely nonwhite, and had higher rates of over-the-counter analgesic medicine prescriptions provided at discharge. Higher-income patients were likely white and non-Hispanic, presented to the ED sooner, and were less likely to receive a prescription for a nonopioid analgesic medicine.

Conclusions

Socioeconomic status is associated with different nonopioid analgesic prescription patterns in children treated in the ED for a long-bone fracture, but had no effect on opioid analgesic prescriptions.
Effectiveness of a Lay Counselor–Led Combination Intervention for Retention of Mothers and Infants in HIV Care: A Randomized Trial in Kenya
Authors: Fayorsey Ruby N. , Wang Chunhui , Chege Duncan , Reidy William , Syengo Masila , Owino Samuel O. , Koech Emily , Sirengo Martin , Hawken Mark P. , Abrams Elaine J.
Published: November 2018

Background:

Retention of mothers and infants across the prevention of mother-to-child HIV transmission (PMTCT) continuum remains challenging. We assessed the effectiveness of a lay worker administered combination intervention compared with the standard of care (SOC) on mother–infant attrition.

Methods:

HIV-positive pregnant women starting antenatal care at 10 facilities in western Kenya were randomized using simple randomization to receive individualized health education, retention/adherence support, appointment reminders, and missed visit tracking vs. routine care per guidelines. The primary endpoint was attrition of mother–infant pairs at 6 months postpartum. Attrition was defined as the proportion of mother–infant pairs not retained in the clinic at 6 months postpartum because of mother or infant death or lost to follow-up. Intent-to-treat analysis was used to assess the difference in attrition. This trial is registered with ClinicalTrials.gov; NCT01962220.

Results:

From September 2013 to June 2014, 361 HIV-positive pregnant women were screened, and 340 were randomized to the intervention (n = 170) or SOC (n = 170). Median age at enrollment was 26 years (interquartile range 22–30); median gestational age was 24 weeks (interquartile range 17–28). Overall attrition of mother–infant pairs was 23.5% at 6 months postpartum. Attrition was significantly lower in the intervention arm compared with SOC (18.8% vs. 28.2%, relative risk (RR) = 0.67, 95% confidence interval: 0.45 to 0.99, P = 0.04). Overall, the proportion of mothers who were retained and virally suppressed (<1000 copies/mL) at 6 months postpartum was 54.4%, with no difference between study arms.

Conclusions:

Provision of a combination intervention by lay counselors can decrease attrition along the PMTCT cascade in low-resource settings.
Outcomes for popliteal artery injury repair after discharge: A large-scale population-based analysis
Authors: Butler William J. , Calvo Richard Y. , Sise Michael J. , Bowie Jason M. , Wessels Lyndsey E. , Bansal Vishal , Beth Sise C.
Published: November 2018

BACKGROUND

Although short-term outcomes for popliteal artery injury after endovascular versus open repair appear similar, studies on outcomes after discharge are limited. We evaluated popliteal artery injury repair in a population-based data set. We hypothesized that postdischarge outcomes for open repair are superior to endovascular repair.

METHODS

Patients with popliteal artery injury were identified in the California Office of Statewide Health Planning and Development 2007–2014 discharge database. Popliteal artery injury and other lower-extremity injuries were identified using International Classification of Diseases, Ninth Revision, Clinical Modification diagnosis codes. Procedure codes were evaluated to identify open repair, endovascular repair, fasciotomy, and amputation. Primary outcomes were mortality or amputation. The association between repair method and each outcome was evaluated with logistic regression. Postdischarge amputation and all-cause mortality were evaluated using survival analysis.

RESULTS

Among 769 patients with popliteal artery injury, open repair occurred in 456 (59.3%), endovascular repair in 37 (4.3%), combined endovascular and open in 18 (2.3%), and nonoperative management in 258 (33.6%). Fasciotomy was performed more frequently in open than endovascular repair (p = 0.001) during index admission. Amputation rate was also increased in open repair, but this was not significant (p = 0.196). Arterial thromboembolus during index admission was more likely after endovascular or combined endovascular and open compared with open (24.3%, 55.6%, 16.7%, respectively, p < 0.001). Patients requiring both endovascular and open were more likely to undergo amputation postdischarge (hazard ratio, 4.11; 95% confidence interval, 1.16–14.53). Patients undergoing endovascular repair were more likely to die postdischarge (hazard ratio, 4.43; 95% confidence interval, 1.06–18.56) compared with patients who had open repair (median, 98.5 days postdischarge).

CONCLUSIONS

In a large cohort with popliteal artery injury, open repair was associated with lower rates of index admission arterial thromboembolus as well as postdischarge amputation and all-cause mortality. We recommend conducting a prospective multicenter study to examine the appropriate use of endovascular repair for this injury.

LEVEL OF EVIDENCE

Therapeutic, level IV.
Isoform 6–selective histone deacetylase inhibition reduces lesion size and brain swelling following traumatic brain injury and hemorrhagic shock
Authors: Nikolian Vahagn C. , Dennahy Isabel S. , Weykamp Michael , Williams Aaron M. , Bhatti Umar F. , Eidy Hassan , Ghandour Mohamed H. , Chtraklin Kiril , Li Yongqing , Alam Hasan B.
Published: November 2018

BACKGROUND

Nonselective histone deacetylase (pan-HDAC) inhibitors, such as valproic acid (VPA), have demonstrated neuroprotective properties in trauma models. However, isoform-specific HDAC inhibitors may provide opportunity for more effective drug administration with fewer adverse effects. We investigated HDAC6 inhibition with ACY-1083 in an in vitro and an in vivo large animal model of injury.

METHODS

Mouse hippocampal cells were subjected to oxygen-glucose deprivation (0% O2, glucose-free and serum-free medium, 18 hours) and reoxygenation (21% O2, normal culture media, 4 hours) with/without VPA (4 mmol/L) or ACY-1083 (30 nmol/L, 300 nmol/L). Cell viability was measured by methylthiazolyl tetrazolium assay. Expression of hypoxia-inducible factor-1α, heat shock protein 70, and effectors in the phosphoinositide-3 kinase/mammalian target of rapamycin pathway were measured by Western blot analysis. Additionally, swine were subjected to combined traumatic brain injury and hemorrhagic shock and randomized to three treatment groups (n = 5/group): (i) normal saline (NS; 3× hemorrhage volume); (ii) NS + VPA (NS; 3× hemorrhage volume, VPA; 150 mg/kg), and (iii) NS + ACY-1083 (NS; 3× hemorrhage volume, ACY-1083; 30 mg/kg). After 6 hours, brain tissue was harvested to assess lesion size and brain swelling.

RESULTS

Significant improvement in cell viability was seen with both HDAC inhibitors in the in vitro study. ACY-1083 suppressed hypoxia-inducible factor-1α expression and up-regulated phosphorylated mammalian target of rapamycin and heat shock protein 70 in a dose-dependent manner. Lesion size and brain swelling in animals treated with pharmacologic agents (VPA and ACY-1083) were both smaller than in the NS group. No differences were observed between the VPA and ACY-1083 treatment groups.

CONCLUSIONS

In conclusion, selective inhibition of HDAC6 is as neuroprotective as nonselective HDAC inhibition in large animal models of traumatic brain injury and hemorrhagic shock.
NF-κB mediates early blood-brain barrier disruption in a rat model of traumatic shock
Authors: Deng Zhe , Liu Dehong , Fu Tingping , Jiang Wenqiang , Qiu Min , Xiao Xiaoyong , Xu Ji , Feng Yongwen , Li Danhui , Zeng Hongke
Published: November 2018

BACKGROUND

Blood-brain barrier (BBB) disruption is associated with a large number of central nervous system and systemic disorders. The aim of the present study was to investigate the dynamic change of BBB changes during traumatic shock and resuscitation as well as the mechanisms involved.

METHODS

The experiments were performed on male Sprague-Dawley rats anesthetized with pentobarbital sodium. To produce traumatic shock, the rats were subjected to bilateral femoral traumatic fracture and blood withdrawal from the femoral artery to decrease mean arterial pressure (MAP) to 35 mm Hg. Hypovolemic status (at a MAP of 35 to 40 mm Hg) was sustained for 1 hour followed by fluid resuscitation with shed blood and 20 mL/kg of lactated Ringer's solution.

RESULTS

The rats were sacrificed at 1 hour, 2 hours, or 6 hours after fluid resuscitation. Blood-brain barrier permeability studies showed that traumatic shock significantly increased brain water contents and sodium fluorescein leakage, which was aggravated by fluid resuscitation. Real-time reverse transcription-polymerase chain reaction (RT-PCR) and Western blot analyses revealed that Na+-K+-Cl− cotransporter-1 and vascular endothelial growth factor (VEGF) expression were upregulated in cortical brain tissue of traumatic shock rats, and this change was accompanied by downregulation of occludin and claudin-5. Traumatic shock also significantly increased the protein levels of NF-κB-p65 subunit. Of note, administration of NF-κB inhibitor PDTC effectively attenuated augmentation of the above changes.

CONCLUSION

Our results suggest that traumatic shock is associated with early BBB disruption, and inhibition of NF-κB may be an effective therapeutic strategy in protecting the BBB under traumatic shock conditions.
FMRP association with and regulation of Fragile X granules exhibit circuit-dependent requirements for the KH2 RNA binding domain
Authors: Gingrich Ellen C. , Shepard Katherine A. , Mitchell Molly E. , Sawicka Kirsty , Darnell Jennifer C. , Akins Michael R.
Published: November 2018

The localization and translation of mRNAs is controlled by a diverse array of ribonucleoprotein particles (RNPs), multimolecular complexes containing mRNAs and RNA binding proteins. Fragile X granules (FXGs) are a family of RNPs that exemplify the diversity of RNA granules in the mammalian nervous system. FXGs are found in a conserved subset of neurons, where they localize exclusively to the axonal compartment. Notably, the specific RNA binding proteins and mRNAs found in FXGs depend on brain circuit and neuron type, with all forebrain FXGs containing Fragile X mental retardation protein (FMRP), the protein mutated in the human autism-related disorder Fragile X syndrome. FMRP negatively regulates FXG abundance but is not required for their association with ribosomes or mRNA. To better understand the circuit-dependent mechanisms whereby FMRP associates with and regulates FXGs, we asked how a disease-causing point mutation, I304N, in the KH2 RNA binding domain of FMRP affects these granules in two brain regions – cortex and hippocampus. We found that FMRPI304N had a reduced association with FXGs, as it was absent from approximately half of FXGs in cortex and nearly all FXGs in hippocampus. FXG abundance correlated with the number of FMRP-containing FXGs, suggesting that FMRP regulates FXG abundance by KH2-independent mechanisms that occur locally within the granules. Together, these findings illustrate that cell type-dependent mechanisms guide the assembly of similar RNA granules. Further, point mutations in RNA granule components may lead to cell type-dependent phenotypes that produce atypical forms of disorders that normally arise from more severe mutations.
Whole cell response to receptor stimulation involves many deep and distributed subcellular processes
Authors: Hansen Jens , Yadaw Arjun Singh , Siddiq Mustafa M. , Tolentino Rosa , Rabinovich Vera , Jayaraman Gomathi , Jain Mohit , Liu Tong , Li Hong , Goldfarb Joseph , Iyengar Ravi
Published: November 2018

Neurite outgrowth is an integrated whole cell response regulated by cannabinoid-1 receptor. To understand underlying mechanisms, we identified subcellular processes (SCPs) and their interactions required for the response. Differentially expressed genes and proteins upon receptor stimulation of neuronal cells were used informatically to build networks of SCPs and their interactions. From SCP networks we identified additional genes, which when ablated validated the SCP involvement in neurite outgrowth. The experiments and informatics analyses identified diverse SCPs such as those involved in pyrimidine metabolism, lipid biosynthesis, mRNA splicing and stability along with membrane vesicle and microtubule dynamics. We find that SCPs required for neurite outgrowth are widely distributed among constitutive cellular functions. Several of these SCPs are deep since they are distal to cell signaling pathways and proximal SCPs involved in microtubule growth and membrane vesicle dynamics. We conclude that receptor regulation of SCPs for neurite outgrowth is distributed and deep.
Human brain activity during mental imagery exhibits signatures of inference in a hierarchical generative model
Authors: Breedlove Jesse , St-Yves Ghislain , Olman Cheryl , Naselaris Thomas
Published: November 2018

Humans have long wondered about the function of mental imagery and its relationship to vision. Although visual representations are utilized during imagery, the computations they subserve are unclear. Building on a theory that treats vision as inference about the causes of sensory stimulation in an internal generative model, we propose that mental imagery is inference about the sensory consequences of predicted or remembered causes. The relation between these complementary inferences yields a relation between the brain activity patterns associated with imagery and vision. We show that this relation has the formal structure of an echo that makes encoding of imagined stimuli in low-level visual areas resemble the encoding of seen stimuli in higher areas. To test for evidence of this echo effect we developed imagery encoding models—a new tool for revealing how imagined stimuli are encoded in brain activity. We estimated imagery encoding models from brain activity measured with fMRI while human subjects imagined complex visual stimuli, and then compared these to visual encoding models estimated from a matched viewing experiment. Consistent with an echo effect, imagery encoding models in low-level visual areas exhibited decreased spatial frequency preference and larger, more foveal receptive fields, thus resembling visual encoding models in high-level visual areas where imagery and vision appeared to be almost interchangeable. Our findings support an interpretation of mental imagery as a predictive inference that is conditioned on activity in high-level visual cortex, and is related to vision through shared dependence on an internal model of the visual world.
Intramolecular domain dynamics regulate synaptic MAGUK protein interactions
Authors: Rademacher Nils , Kuropka Benno , Kunde Stella-Amrei , Wahl Markus C. , Freund Christian , Shoichet Sarah A.
Published: November 2018

PSD-95 MAGUK family scaffold proteins are multi-domain organisers of synaptic transmission that contain three PDZ domains followed by an SH3-GK domain tandem. This domain architecture allows coordinated assembly of protein complexes composed of neurotransmitter receptors, synaptic adhesion molecules, cytoskeletal proteins and downstream signalling effectors. Here we show that binding of monomeric PDZ3ligands to the third PDZ domain of PSD-95 induces functional changes in the intramolecular SH3-GK domain assembly that influence subsequent homotypic and heterotypic complex formation. We identify PSD-95 interactors that differentially bind to the SH3-GK domain tandem depending on its conformational state. Among these interactors we further establish the heterotrimeric G protein subunit Gnb5 as a PSD-95 complex partner at dendritic spines. The PSD-95 GK domain binds to Gnb5 and this interaction is triggered by PDZ3ligands binding to the third PDZ domain of PSD-95, unraveling a hierarchical binding mechanism of PSD-95 complex formation.
CMT disease 2A and demyelination decouple ATP and ROS production by axonal mitochondria
Authors: van Hameren Gerben , Campbell Graham , Deck Marie , Berthelot Jade , Chrast Roman , Tricaud Nicolas
Published: November 2018

Mitochondria are critical for the function and maintenance of myelinated axons notably through ATP production. A by-product of this activity is reactive oxygen species (ROS), which are highly deleterious for neurons. While ROS and metabolism are involved in several neurodegenerative diseases, it is still unclear how axonal activity or myelin modulates ATP and ROS production in axonal mitochondria. We imaged and quantified mitochondrial ATP and hydrogen peroxide (H2O2) in resting or stimulated peripheral nerve myelinated axonsin vivo, using genetically-encoded fluorescent probes, two-photon time-lapse and CARS imaging. ATP and H2O2productions are intrinsically higher in nodes of Ranvier even in resting conditions. Axonal firing increased both ATP and H2O2productions but with different dynamics. In neuropathic MFN2R94Qmice, mimicking Charcot-Marie-Tooth 2A disease, defective mitochondria failed to upregulate ATP production following axonal activity. However, H2O2production was dramatically sustained. Mimicking demyelinating peripheral neuropathy resulted in a reduced production of ATP while H2O2level soared. Taken together, our results suggest that ATP and ROS productions are decoupled under neuropathic conditions, which may compromise axonal function and integrity.
How does genome size affect the evolution of pollen tube growth rate, a haploid performance trait?
Authors: Reese John B. , Williams Joseph H.
Published: November 2018

Premise of the Study

Male gametophytes of most seed plants deliver sperm to eggs via a pollen tube. Pollen tube growth rates (PTGRs) of angiosperms are exceptionally rapid, a pattern attributed to more effective haploid selection under stronger pollen competition. Paradoxically, whole genome duplication (WGD) has been common in angiosperms but rare in gymnosperms. Pollen tube polyploidy should initially acceleratePTGRbecause increased heterozygosity and gene dosage should increase metabolic rates, however polyploidy should also independently increase tube cell size, causing more work which should decelerate growth. We asked how genome size changes have affected the evolution of seed plantPTGRs.

Methods

We assembled a phylogenetic tree of 451 species with knownPTGRs. We then used comparative phylogenetic methods to detect effects of neo-polyploidy (within-genus origins), DNA content, and WGD history onPTGR, and correlated evolution ofPTGRand DNA content.

Key Results

Gymnosperms had significantly higher DNA content and slowerPTGRoptima than angiosperms, and theirPTGRand DNA content were negatively correlated. For angiosperms, 89% of model weight favored Ornstein-Uhlenbeck models with a fasterPTGRoptimum for neo-polyploids, butPTGRand DNA content were not correlated. In comparisons of within-genus and intraspecific-cytotype pairs,PTGRsof neo-polyploids ≤ paleo-polyploids.

Conclusions

Genome size increases should negatively affectPTGRwhen genetic consequences of WGDs are minimized, as found in intra-specific autopolyploids (low heterosis) and gymnosperms (few WGDs). But in angiosperms, the higherPTGRoptimum of neo-polyploids and non-negativePTGR-DNA content correlation suggest that recurrent WGDs have caused substantialPTGRevolution in a non-haploid state.