bluuebunny/crossref_metadata_2025 huggingface dataset:
XueBiJing Injection Versus Placebo for Critically Ill Patients With Severe Community-Acquired Pneumonia: A Randomized Controlled Trial
Authors: Song Yuanlin , Yao Chen , Yao Yongming , Han Hui , Zhao Xiaodong , Yu Kaijiang , Liu Luyi , Xu Ying , Liu Zhongmin , Zhou Qingshan , Wang Ying , Ma Zhuang , Zheng Youguang , Wu Dawei , Tang Zhongzhi , Zhang Minzhou , Pan Shuming , Chai Yanfen , Song Yan , Zhang Jian , Pan Lei , Liu Yi , Yu He , Yu Xuezhong , Zhang Hong , Wang Xiaoge , Du Zhaohui , Wan Xianyao , Tang Yijun , Tian Yingping , Zhu Yimin , Wang Hongliang , Yan Xiaoyan , Liu Zhi , Zhang Boli , Zhong Nanshan , Shang Hongcai , Bai Chunxue
Published: June 2019

Objectives:

To investigate whether XueBiJing injection improves clinical outcomes in critically ill patients with severe community-acquired pneumonia.

Design:

Prospective, randomized, controlled study.

Setting:

Thirty-three hospitals in China.

Patients:

A total of 710 adults 18–75 years old with severe community-acquired pneumonia.

Interventions:

Participants in the XueBiJing group received XueBiJing, 100 mL, q12 hours, and the control group received a visually indistinguishable placebo.

Measurements and Main Results:

The primary outcome was 8-day improvement in the pneumonia severity index risk rating. Secondary outcomes were 28-day mortality rate, duration of mechanical ventilation and total duration of ICU stay. Improvement in the pneumonia severity index risk rating, from a previously defined endpoint, occurred in 203 (60.78%) participants receiving XueBiJing and in 158 (46.33%) participants receiving placebo (between-group difference [95% CI], 14.4% [6.9–21.8%]; p < 0.001). Fifty-three (15.87%) XueBiJing recipients and 84 (24.63%) placebo recipients (8.8% [2.4–15.2%]; p = 0.006) died within 28 days. XueBiJing administration also decreased the mechanical ventilation time and the total ICU stay duration. The median mechanical ventilation time was 11.0 versus 16.5 days for the XueBiJing and placebo groups, respectively (p = 0.012). The total duration of ICU stay was 12 days for XueBiJing recipients versus 16 days for placebo recipients (p = 0.004). A total of 256 patients experienced adverse events (119 [35.63%] vs 137 [40.18%] in the XueBiJing and placebo groups, respectively [p = 0.235]).

Conclusions:

In critically ill patients with severe community-acquired pneumonia, XueBiJing injection led to a statistically significant improvement in the primary endpoint of the pneumonia severity index as well a significant improvement in the secondary clinical outcomes of mortality, duration of mechanical ventilation and duration of ICU stay.
Fluid Overload Associates With Major Adverse Kidney Events in Critically Ill Patients With Acute Kidney Injury Requiring Continuous Renal Replacement Therapy
Authors: Woodward Connor W. , Lambert Joshua , Ortiz-Soriano Victor , Li Ye , Ruiz-Conejo Marice , Bissell Brittany D. , Kelly Andrew , Adams Paul , Yessayan Lenar , Morris Peter E. , Neyra Javier A.
Published: June 2019

Objectives:

We examined the association between fluid overload and major adverse kidney events in critically ill patients requiring continuous renal replacement therapy for acute kidney injury.

Design:

Retrospective cohort study.

Setting:

ICU in a tertiary medical center.

Patients:

Four-hundred eighty-one critically ill adults requiring continuous renal replacement therapy for acute kidney injury.

Interventions:

None.

Measurements and Main Results:

Fluid overload was assessed as fluid balance from admission to continuous renal replacement therapy initiation, adjusted for body weight. Major adverse kidney events were defined as a composite of mortality, renal replacement therapy-dependence or inability to recover 50% of baseline estimated glomerular filtration rate (if not on renal replacement therapy) evaluated up to 90 days after discharge. Patients with fluid overload less than or equal to 10% were less likely to experience major adverse kidney events than those with fluid overload greater than 10% (71.6% vs 79.4%; p = 0.047). Multivariable logistic regression showed that fluid overload greater than 10% was associated with a 58% increased odds of major adverse kidney events (p = 0.046), even after adjusting for timing of continuous renal replacement therapy initiation. There was also a 2.7% increased odds of major adverse kidney events for every 1 day increase from ICU admission to continuous renal replacement therapy initiation (p = 0.024). Fluid overload greater than 10% was also found to be independently associated with an 82% increased odds of hospital mortality (p = 0.004) and 2.5 fewer ventilator-free days (p = 0.044), compared with fluid overload less than or equal to 10%.

Conclusions:

In critically ill patients with acute kidney injury requiring continuous renal replacement therapy, greater than 10% fluid overload was associated with higher risk of 90-day major adverse kidney events, including mortality and decreased renal recovery. Increased time between ICU admission and continuous renal replacement therapy initiation was also associated with decreased renal recovery. Fluid overload represents a potentially modifiable risk factor, independent of timing of continuous renal replacement therapy initiation, that should be further examined in interventional studies.
Ambient Particulate Air Pollution and Blood Pressure in Peri-urban India
Authors: Curto Ariadna , Wellenius Gregory A. , Milà Carles , Sanchez Margaux , Ranzani Otavio , Marshall Julian D. , Kulkarni Bharati , Bhogadi Santhi , Kinra Sanjay , Tonne Cathryn
Published: June 2019

Background:

Evidence linking long-term exposure to particulate air pollution to blood pressure (BP) in high-income countries may not be transportable to low- and middle-income countries. We examined cross-sectional associations between ambient fine particulate matter (PM2.5) and black carbon (BC) with BP (systolic [SBP] and diastolic [DBP]) and prevalent hypertension in adults from 28 peri-urban villages near Hyderabad, India.

Methods:

We studied 5531 participants from the Andhra Pradesh Children and Parents Study (18–84 years, 54% men). We measured BP (2010–2012) in the right arm and defined hypertension as SBP ≥130 mmHg and/or DBP ≥80 mmHg. We used land-use regression models to estimate annual average PM2.5 and BC at participant’s residence. We applied linear and logistic nested mixed-effect models stratified by sex and adjusted by cooking fuel type to estimate associations between within-village PM2.5 or BC and health.

Results:

Mean (SD) PM2.5 was 33 µg/m3 (2.7) and BC was 2.5 µg/m3 (0.23). In women, a 1 µg/m3 increase in PM2.5 was associated with 1.4 mmHg higher SBP (95% confidence interval [CI]: 0.12, 2.7), 0.87 mmHg higher DBP (95% CI: −0.18, 1.9), and 4% higher odds of hypertension (95% CI: 0%, 9%). In men, associations with SBP (0.52 mmHg; 95% CI: −0.82, 1.8), DBP (0.41 mmHg; 95% CI: −0.69, 1.5), and hypertension (2% higher odds; 95% CI: −2%, 6%) were weaker. No associations were observed with BC.

Conclusion:

We observed a positive association between ambient PM2.5 and BP and hypertension in women. Longitudinal studies in this region are needed to corroborate our findings.
Accountability Assessment of Health Improvements in the United States Associated with Reduced Coal Emissions Between 2005 and 2012
Authors: Henneman Lucas R. F. , Choirat Christine , Zigler Corwin M.
Published: June 2019

Background:

National, state, and local policies contributed to a 65% reduction in sulfur dioxide emissions from coal-fired power plants between 2005 and 2012 in the United States, providing an opportunity to directly quantify public health benefits attributable to these reductions under an air pollution accountability framework.

Methods:

We estimate ZIP code-level changes in two different—but related—exposure metrics: total PM2.5 concentrations and exposure to coal-fired power plant emissions. We associate changes in 10 health outcome rates among approximately 30 million US Medicare beneficiaries with exposure changes between 2005 and 2012 using two difference-in-difference regression approaches designed to mitigate observed and unobserved confounding.

Results:

Rates per 10,000 person–years of six cardiac and respiratory health outcomes—all cardiovascular disease, chronic obstructive pulmonary disorder, cardiovascular stroke, heart failure, ischemic heart disease, and respiratory tract infections—decreased by between 7.89 and 1.95 per

JOURNAL/epide/04.03/00001648-201907000-00003/inline-graphic1/v/2023-09-08T093821Z/r/image-tiff

decrease in PM2.5, with comparable decreases in coal exposure leading to slightly larger rate decreases. Results for acute myocardial infarction, heart rhythm disorders, and peripheral vascular disease were near zero and/or mixed between the various exposure metrics and analyses. A secondary analysis found that nonlinearities in relationships between changing health outcome rates and coal exposure may explain differences in their associations.

Conclusions:

The direct analyses of emissions reductions estimate substantial health benefits via coal power plant emission and PM2.5 concentration reductions. Differing responses associated with changes in the two exposure metrics underscore the importance of isolating source-specific impacts from those due to total PM2.5 exposure.
A New and Simple TRG Multiplex PCR Assay for Assessment of T‐cell Clonality: A Comparative Study from the EuroClonality Consortium
Authors: Armand Marine , Derrieux Coralie , Beldjord Kheira , Wabeke Tamara , Lenze Dido , Boone Elke , Bruggemann Monika , Evans Paul A.S. , Gameiro Paula , Hummel Michael , Villarese Patrick , Groenen Patricia J.T.A. , Langerak Anton W. , Macintyre Elizabeth A. , Davi Frederic
Published: June 2019

Supplemental Digital Content is available in the text
Endoscopic Orbital Decompression by Oculoplastic Surgeons for Proptosis in Thyroid Eye Disease
Authors: Juniat Valerie , Abbeel Laura , McGilligan J. Anthony , Curragh David , Selva Dinesh , Rajak Saul
Published: June 2019

The authors report the outcomes of a series of endonasal orbital decompression carried out by oculoplastic surgeons.

Purpose:

Orbital decompression is an established surgical treatment option for a range of orbital conditions. Traditionally, Ear, Nose and Throat surgeons have adopted the endoscopic route while ophthalmologists operate via an external approach. The authors report the outcomes of endonasal decompression performed by oculoplastic surgeons experienced in endonasal techniques.

Methods:

This was a retrospective case series of patients who underwent endoscopic orbital decompression for proptosis secondary to thyroid eye disease across 2 hospital sites between January 2011 and July 2018. Inclusion criteria were patients who had endoscopic decompression for proptosis in inactive thyroid eye disease or active disease without dysthyroid optic neuropathy. Information collected includes patient demographics, diagnosis, surgical details, preoperative and postoperative clinical findings (including, visual acuity, color vision, exophthalmometry readings, palpebral aperture, intraocular pressure, ocular motility, diplopia, and visual field), complications, and further treatment.

Results:

There were 70 cases of endoscopic decompression. The majority of patients had endoscopic medial and posterior medial wall/floor decompression (44.3%; 31/70 cases). Visual acuity remained stable in 98.6% (69/70). There was an average reduction in proptosis of 3.5 ± 1.2 mm (standard deviation [SD]) in the endoscopic medial wall only group, 3.9 ± 0.9 mm (SD) in endoscopic medial wall and posterior medial portion of the floor group, and 7.6 ± 2.1 mm (SD) in the 3-wall decompression group. Motility improved in 11.4% (8/70) and worsened in 2.9% (2/70). There were no significant intraoperative or postoperative complications associated with endoscopic surgery.

Conclusions:

Oculoplastic surgeons experienced in endonasal techniques can perform endoscopic orbital decompression with outcomes comparable to the literature.
Screening Criteria for Detecting Severe Ocular Injuries in the Setting of Orbital Fractures
Authors: Richani Karina , Do Thai H. , Merritt Helen A. , Pfeiffer Margaret L. , Chuang Alice Z. , Phillips Margaret E.
Published: June 2019

Severe ocular injury associated with orbital wall fracture is more likely in patients with 2 or more ophthalmic signs or symptoms.

Purpose:

Define incidence of severe ocular trauma in orbital fracture patients and determine if ocular signs and symptoms are useful predictors of severe ocular injuries.

Methods:

Retrospective chart review was performed on all patients with orbital fractures between April 1, 2013, and December 31, 2014. Patients were included if they had radiographic evidence of acute fracture of at least one orbital wall and were evaluated by the Ophthalmology service. Demographics, concurrent injury data, and symptoms and signs of ocular trauma were collected. Concurrent ocular injuries were grouped by severity. Predictive signs or symptoms for severe ocular trauma were identified by stepwise logistic regression analysis. The threshold point for predictive signs and symptoms was detected by a receiver operating characteristic (ROC).

Results:

Five-hundred-twelve patients were included. The most common mechanisms of injury were assault (39%), fall (25%), and motor vehicle accident (21%). The incidence of any concurrent ocular trauma was 75% (383/512), with 14% (70/512) being severe. Four signs and symptoms were predictors of severity: blurred vision (P < 0.0001), pain with eye movements (P < 0.0001), visual acuity worse than 20/40 in the ipsilateral eye (P < 0.001), and restricted motility (P < 0.001). The presence of 2 or more of these signs or symptoms was predictive of severe ocular trauma with high sensitivity (91%) and specificity (86%).

Conclusions:

In cooperative patients with acute orbital wall fractures, the presence of 2 or more signs or symptoms is predictive of severe ocular trauma and necessitates the need for urgent ophthalmic consultation.
Clostridium septicum Triad
Authors: Onuorah Luke N. , Czachor John S.
Published: June 2019

Infected aortic aneurysm is a rare occurrence accounting for 2.6% of described aneurysms. Staphylococcus species and Salmonella species are the most frequently isolated microbes, with Clostridium septicum being decidedly less commonly detected. It is well documented that C. septicum bacteremia in the presence of an infected aneurysm is strongly associated with gastrointestinal cancer, particularly colorectal adenocarcinoma. Although blood cultures were repeatedly negative, a left pleural effusion culture grew C. septicum. The patient was treated with an endovascular prosthesis and prolonged antibiotic therapy including lifelong suppression. Serial abdominal computed tomographic scans with contrast displayed an enlarging appendiceal lesion that was described as a mucocele. Surgical histopathology revealed an invasive moderately differentiated adenocarcinoma. This case highlights both the association of C. septicum with malignancy and the utility of pleural effusion culture in the presence of culture-negative infected aortic aneurysm.
Types of Polydrug Use Among Spanish Students in Health Sciences
Authors: Font-Mayolas Sílvia , Hernández-Serrano Olga , Gras Maria E. , Sullman Mark J. M.
Published: June 2019

Polydrug use among university students may be a predictor for established patterns of multiple substance use and potentially entail long-term health problems. This study examined the types of polydrug use among Spanish students in health sciences. Undergraduate students (n = 968), aged 18–38 years (M = 21.09 years, SD = 4.10), completed the survey. A percentage of 44.3% of the participants were classified as polydrug users. Type A users (alcohol and cigarettes) made up 17.8% of the participants surveyed, whereas 20.1% were Type B (cannabis with cigarettes and/or alcohol), and a further 5.7% were Type C (cannabis with cigarettes and/or alcohol, plus at least another kind of illegal drug). Type A was the most common type among women, whereas Type C was the most common among men. Type B use was higher among women 18–19 years old than among women 25–29 years old, whereas there were no female Type C users younger than 20 years old. Weekend consumption was higher, than weekday consumption, across all polydrug user types and substances. These results suggest that the prevalence of polydrug use among Spanish students in health sciences was similar to students in other disciplines, with Type B as the most prevalent among healthcare and nonhealthcare students. Taking into account the differences based on gender, age, and time of consumption, a specific approach to the different typologies of polydrug users might be a vital step in the successful development of preventive interventions tailored to the changing reality of psychoactive substance use.
Association of Postpartum Smoking Relapse With Breastfeeding and Body Mass Index
Authors: Duman Mesude , Timur Taşhan Sermin , Durgun Ozan Yeter
Published: June 2019

Objective:

This study aimed to determine the relationship between smoking relapse and breastfeeding and body mass index in the postpartum period.

Methods:

This descriptive, cross-sectional study was conducted between November 2016 and November 2017 in the polyclinic for children’s health and common illnesses at a university hospital in eastern Turkey. One hundred eleven women who met the inclusion criteria constituted the sample of the study. The data were evaluated using the analyses of percentage, arithmetic mean, standard deviation, independent-samples t test, analysis of variance, and multiple linear regression.

Results:

In the study, the week of pregnancy period when the women quit smoking was 8.19 ± 5.17, and the week of postpartum smoking relapse was 8.47 ± 11.76. Furthermore, 72.1% of the women stated that they wanted to quit smoking permanently. The study determined that the status of wanting to quit smoking permanently, the status of smoking while breastfeeding, and gained weight during the last gestation are important predictors of postpartum smoking relapse.

Originality and Value:

Knowledge on the characteristics of the women who started smoking again in the postpartum period is important for helping women who have quitted smoking in pregnancy but who are prone to relapse as a risk group by health care personnel.
A Novel Text Message Intervention to Improve Adherence to Stimulants in Adults With Attention Deficit/Hyperactivity Disorder
Authors: Biederman Joseph , Fried Ronna , DiSalvo Maura , Woodworth K. Yvonne , Biederman Itai , Noyes Elizabeth , Faraone Stephen V. , Perlis Roy H.
Published: June 2019

Background

Attention deficit/hyperactivity disorder (ADHD) is a prevalent neurobiological disorder associated with a wide range of adverse outcomes. Although large data sets document that stimulants decrease the risks for many ADHD-associated adverse outcomes, compliance with stimulants remains very poor. The main aim of this study was to assess the effectiveness of a novel text messaging–based intervention aimed at improving the poor rate of adherence to stimulant medications in adults with ADHD.

Methods

Subjects were adults with ages 18 to 55, prescribed a stimulant medication for ADHD treatment. For comparators, we identified at a 5-to-1 ratio (age and sex matched) adult patients from the Partners HealthCare electronic medical record who had been prescribed stimulant medications over a 1-year period. We determined whether patients had timely prescription refills, defined as refilled within 37 days, using prescriptions documented in their electronic medical record.

Results

Our results showed that 68% of the SMS intervention group refilled their prescriptions in a timely manner. In contrast, only 34% of patients receiving treatment as usual refilled their prescriptions in a timely fashion (odds ratio, 4.04; 95% confidence interval, 2.49–6.56; P < 0.001).

Conclusions

These data indicate that an innovative ADHD-centric text messaging intervention significantly improved patient engagement to treatment with stimulants in adults with ADHD. Findings provide strong support for the use of a readily accessible, inexpensive, and widely available technology to improve the poor rate of adherence to stimulant treatment in adults with ADHD. To the best of our knowledge, this study is the first digital health intervention aimed at improving adherence to stimulant medication for adults with ADHD.
The Development of a Standardized Framework for Primary Nurse Specialists in Diabetes Care in China: A Delphi Study
Authors: XING Qiuling , ZHANG Mingxia , ZHAO Fang , ZHOU Yingxia , MO Yongzhen , YUAN Li
Published: June 2019

Background:

The number of patients with diabetes has been increasing rapidly according to a 2017 report by the International Diabetes Federation. Diabetes has become one of the most challenging public health problems, and there will be an estimated 143 million patients with diabetes in China by 2035. This puts considerable pressure on nurses who specialize in the care of patients with diabetes in China and increases related social and financial burdens. Clinical practice has proven that strengthening the core competencies of nurses and establishing an evaluation system of core competencies improve both healthcare quality and patient quality of life. However, no core-competence system framework currently addresses the unique characteristics of nurses in China.

Purposes:

The purpose of this study was to construct a core-competence system framework for primary nurse specialists in diabetes care.

Methods:

A brainstorming approach was conducted that worked to conceptualize the core competencies of nurse specialists in diabetes care in China. Next, a study group organized this information and conducted a seminar; 50 experts and patients with diabetes were invited to develop the first draft of the framework. Afterward, 50 experts were selected to participate in the Delphi survey. Most indicators were retained after a three-round Delphi process, and the superiority chart was used to determine the weights of the six dimensions.

Results:

Forty-seven experts completed the consultation. The experts' rate of response ranged from 94% to 100%, the authority coefficient was .91, and the Kendall's coefficients of concordance in Grades 1–3 were .793, .418, and .542, respectively. An increasingly detailed, three-grade system framework was developed, including six first-grade indicators (diabetes professional knowledge, diabetes-related knowledge, communication skills and health education ability, specialized skills, clinical judgment, and specialty development capacity), 23 second-grade indicators, and 87 third-grade indicators. The weights of the six first-grade indicators were .221, .149, .192, .209, .160, and .069, respectively.

Conclusions:

The core-competence system framework includes six core competencies, which represent the main characteristics of primary nurse specialists in diabetes care who are highly recommended by experts. It is important to keep in mind that this is only a theoretical framework and thus must be further tested in clinical practice settings in China.
Clinical Treatment of Pediatric Primary Cardiac Tumors: A Single-Institute 12-Year Experience
Authors: Ding Peicheng , Qi Jirong , Mo Ran , Sun Jian , Pen Wei , Wu Kaihong , Qian Longbao , Mo Xuming
Published: June 2019

Background:

Primary cardiac tumors in children are extremely rare. This study aimed to analyze clinical treatment and follow-up of pediatric primary cardiac tumors.

Patients and Methods:

We performed a retrospective analysis by searching the medical records of 75 patients diagnosed with pediatric primary cardiac tumors from June 2005 to August 2017 in our institution. We followed operative patients every half year in the first postoperative year and then at least every year. If the patients had no serious symptoms or hemodynamic changes, they received nonoperative management and were followed regularly every year.

Results:

Nineteen patients underwent surgery at our department for serious symptoms and critical hemodynamic changes. Four patients had postoperative complications. Two died of low cardiac output syndrome and arrhythmia after surgery. One patient with myxomas had tumor recurrence and one had been found of another rhabdomyoma after surgery. The other 14 patients recovered well. Fifty-six patients had nonoperative management. Four were lost in follow-up. Two patients with malignant tumors died of unknown causes after discharge. The remaining patients had no severe symptoms or tumor growth during follow-up.

Conclusions:

Clinical treatment of pediatric primary cardiac tumors should be performed individually. Most pediatric primary cardiac tumors are benign, and spontaneous regression is possible, especially for rhabdomyomas. The principle purpose of surgical treatment is to restore normal hemodynamics and protect important structures and cardiac tissue.
Exploring a Nursing Home–Specific Interdisciplinary Approach
Authors: Park Min Sun , Lee Su Jung , Chang Sung Ok
Published: June 2019

The number of elderly suffering from dementia and complex disabilities is gradually increasing in nursing homes, and they form a differentiated group that requires palliative care provided by practitioners in various disciplines from the time of their admission to improve the quality of their remaining lives. The purpose of this study was to explore an interdisciplinary care approach by nurses and related practitioners for the demented and complex-disabled elderly in nursing homes that focuses on palliative care based on an ethical point of view. A qualitative thematic analysis was conducted through in-depth interviews of 29 interdisciplinary practitioners working at 5 nursing homes. From them, 3 themes and 9 subthemes were extracted as the key results. First, practitioners set up cooperative care plans based on constantly tracking down clues to gradual functional deteriorations. Second, practitioners establish a cooperative committee to link residents and practitioners for responding to the subtle expressions of the elderly. Finally, practitioners maximize the opportunities for improving the quality of the elderly’s remaining lives. These results can be the basis for the first prototype in developing interdisciplinary practical guidelines for nursing home–specific palliative care and can provide new insights for the practical care concept of palliative care.
Spontaneous Breathing Trial for Prediction of Extubation Success in Pediatric Patients Following Congenital Heart Surgery: A Randomized Controlled Trial*
Authors: Ferreira Felipe V. , Sugo Edward K. , Aragon Davi C. , Carmona Fabio , Carlotti Ana P. C. P.
Published: June 2019

Objectives:

To evaluate the usefulness of a spontaneous breathing trial for predicting extubation success in pediatric patients in the postoperative period after cardiac surgery compared with a physician-led weaning.

Study Design:

Randomized, controlled trial.

Setting:

PICU of a tertiary-care university hospital.

Patients:

A population of pediatric patients following cardiac surgery for congenital heart disease.

Interventions:

Patients on mechanical ventilation for more than 12 hours after surgery who were considered ready for weaning were randomized to the spontaneous breathing trial group or the control group. The spontaneous breathing trial was performed on continuous positive airway pressure with the pressure support of 10 cmH2O, the positive end-expiratory pressure of 5 cmH2O, and the fraction of inspired oxygen less than or equal to 0.5 for 2 hours. Patients in the control group underwent ventilator weaning according to clinical judgment.

Measurements and Main Results:

The primary endpoint was extubation success defined as no need for reintubation within 48 hours after extubation. Secondary outcomes were PICU length of stay, hospital length of stay, occurrence rate of ventilator-associated pneumonia, and mortality. One hundred and ten patients with the median age of 8 months were included in the study: 56 were assigned to the spontaneous breathing trial group and 54 were assigned to the control group. Demographic and clinical data and Risk Adjustment for Congenital Heart Surgery-1 classification were similar in both groups. Patients undergoing the spontaneous breathing trial had greater extubation success (83% vs 68%, p = 0.02) and shorter PICU length of stay (median 85 vs 367 hr, p < 0.0001) compared with the control group, respectively. There was no significant difference between groups in hospital length of stay, occurrence rate of ventilator-associated pneumonia, and mortality.

Conclusions:

Pediatric patients with congenital heart disease undergoing the spontaneous breathing trial postoperatively had greater extubation success and shorter PICU length of stay compared with those weaned according to clinical judgment.
EBV-Associated T-Cell Lymphoproliferative Disorders Demonstrated on FDG PET/CT in a Patient With Hemophagocytic Lymphohistiocytosis
Authors: Hao Ruirui , Yang Xu , Liu Zhimou , Yang Jigang
Published: June 2019

FDG PET/CT was performed in a 20-year-old woman to find the underlying cause of hemophagocytic lymphohistiocytosis. The images revealed hypermetabolic activity in multiple lymph nodes and in the spleen. Lymphoma was suspected. However, the pathology of bone marrow, lymph nodes, and the spleen demonstrated chronic active Epstein-Barr virus–associated T-cell lymphoproliferative disorders.
Complete Regression of Lung Metastases in a Patient With Metastatic Castration-Resistant Prostate Cancer Using 177Lu-PSMA Radioligand Therapy
Authors: Zhang Jingjing , Kulkarni Harshad R. , Singh Aviral , Baum Richard P.
Published: June 2019

Patients with metastatic castration-resistant prostate cancer (mCRPC) and visceral (liver or lung) metastases have a poor prognosis and worse outcomes than those with bone disease with or without lymph nodes involvement. The high prostate-specific membrane antigen expression in prostate cancer metastases makes it a promising approach for targeted radionuclide therapy of prostate cancer. Lutetium-177 (177Lu)–labeled prostate-specific membrane antigen radioligand therapy (177Lu-PRLT) has demonstrated encouraging efficacy in mCRPC. We report here an mCRPC patient with lung, lymph nodes, and extensive bone metastases, who underwent 177Lu-PRLT and had excellent response to the treatment and complete regression of lung metastases after 177Lu-PRLT.
Cerebellar Hypermetabolism in a Case of Paraneoplastic Cerebellar Syndrome With the Primary Lymphoepithelial Carcinoma in Tonsil
Authors: Wang Jingnan , Wang Wenze , Zhao Yang , Cui Ruixue
Published: June 2019

A 70-year-old man with cerebellar syndromes was clinically diagnosed as paraneoplastic cerebellar degeneration and underwent whole-body 18F-FDG PET/CT imaging for screening primary tumor. Intensely elevated tracer uptake in both cerebellar hemispheres was revealed, whereas no abnormality was found in MRI. Increased tracer uptake and swelling of the left tonsil and a cervical lymph node were found at the same time, suggesting neoplasm in tonsil with lymph node metastasis. Pathological examination demonstrated lymphoepithelial carcinoma of the left tonsil.
FDG PET/CT in a Case of Primary Pulmonary Ewing Sarcoma
Authors: Zhang Jun , Dong Aisheng , Cui Yong , Wang Yang
Published: June 2019

Extraskeletal Ewing sarcoma is rare. The common locations of extraskeletal Ewing sarcoma include the paravertebral region, lower extremities, and chest wall. Primary pulmonary Ewing sarcoma is extremely rare. Because Ewing sarcoma is sensitive to specialized chemotherapy regimens, accurate diagnosis is therefore critical. The diagnosis of pulmonary Ewing sarcoma can be challenging and need immunohistochemical and cytogenetic analyses. Imaging findings of pulmonary Ewing sarcoma have been rarely reported. This report describes a case of primary pulmonary Ewing sarcoma with immunohistochemical, cytogenetic, CT, and FDG PET/CT findings.
18F-PSMA 1007 Brain PET/CT Imaging in Glioma Recurrence
Authors: Marafi Fahad , Sasikumar Arun , Fathallah Wael , Esmail Abdulredh
Published: June 2019

A 64-year-old man with a known case of right parietal lobe glioblastoma multiforme operated on in August 2018 was referred for 18F-FDG PET/CT with a clinical suspicion of recurrence. He underwent 18F-FDG and 18F-PSMA 1007 scans. Both the scans showed intense tracer uptake in right parietal lobe lesion, which concurred with MRI findings of recurrent disease and was later proven on histopathologic examination as recurrence. Our case highlights the feasibility of 18F-PSMA 1007 PET/CT imaging of suspected glioblastoma recurrence. Considering its similarity to PSMA-617, it may be used as a surrogate imaging tracer for potential theranostic application using alpha or beta emitters.
Alpha-1 Antitrypsin Attenuates Acute Lung Allograft Injury in a Rat Lung Transplant Model
Authors: Emtiazjoo Amir M. , Hu Hanbo , Lu Li , Brantly Mark L.
Published: June 2019

Background.

Ischemia-reperfusion injury (IRI) after lung transplantation triggers a cascade of inflammatory changes that can contribute to acute allograft injury. This influences both the short- and long-term survival of the lung allograft. Alpha-1 antitrypsin (AAT) is a protease inhibitor with known anti-inflammatory and immune-regulatory properties that mitigate tissue damage. This study explores the protective effects of AAT in the setting of IRI utilizing a rat lung transplant model.

Methods.

Orthotopic left single lung transplantation was performed from Lewis to Sprague-Dawley rats; recipients did not receive systemic immunosuppression. Before transplantation, the donor lungs were primed with either albumin (control) or AAT. Starting the day of transplantation, recipient rats also received either albumin (control) or AAT with subsequent doses administered over the next 7 days. On the eighth postoperative day, lung allografts were recovered and analyzed.

Results.

Degree of inflammatory infiltrate, as quantified by the allograft weight (g)/body weight (kg) ratio, was significantly reduced in the AAT-treated group compared with controls (3.5 vs 7.7, respectively, P < 0.05). Treatment with AAT also significantly decreased allograft necrosis in treated animals, as measured by a semiquantitative score that ranged from 0 to 4 (1.25 vs 4, P < 0.05). In addition, lymphocytes isolated from recipients treatment group showed significant proliferative inhibition via a mixed lymphocyte response assay in response to donor antigens.

Conclusions.

AAT attenuates acute allograft injury and necrosis in a rat model of lung transplantation, suggesting that AAT may play a role in reducing IRI-induced inflammation.
Potential of Membranes Surrounding the Fetus as Immunoprotective Cell-Carriers for Allogeneic Transplantations
Authors: Togarrati Padma Priya , Dinglasan Nuntana , Yee Elizabeth , Heitman John W. , Jackman Rachael P. , Geisberg Mark , Norris Philip J. , Bárcena Alicia , Muench Marcus O.
Published: June 2019

Background.

Membranes surrounding the fetus play a crucial role in providing a physical and immunological barrier between a semiallogeneic fetus and mother during pregnancy. In this study, we tested whether cotransplantation of fetal membranes (FMs) and allogeneic donor cells would improve the retention and function of allografts in mice.

Methods.

Intact and enzyme-digested membranes obtained from E18-E19 pregnant mice were subcutaneously cotransplanted with 10F7MN hybridoma cells that are of BALB/cByJ (Balb) origin and secrete anti-human CD235a antibody. Cells were transplanted into C57BL/6J (B6, allogeneic), Balb (syngeneic), and FVB/NJ (third-party) mice. Serum was collected after 1 and 3 weeks of cell transplantation and tested using flow cytometry for the presence of anti-human CD235a antibody. Immunosuppressive functions of membranes were further investigated by analyzing the cytokine profile of supernatants collected from allo-reactive mixed lymphocyte reactions (MLRs) using a multiplex cytokine assay.

Results.

B6 mice transplanted with 10F7MN cells along with membranes syngeneic to the host had significantly higher levels of CD235a antibody when compared to B6 mice that received cells without membranes, allogenic membranes, or third-party membranes. Syngeneic membranes significantly inhibited T-cell proliferation in the presence of allogeneic stimuli and suppressed the release of Th1-cytokines such as IFNγ, TNFα, and IL-2 in MLRs. Additionally, increases in the levels of Th2-cytokines were found in MLRs containing membrane-derived cells.

Conclusions.

Our study highlights the potential use of syngeneic FMs to act as potent cell-carriers that could improve graft retention as well as graft-specific immunoprotection during allograft transplantation.
Population genomics perspectives on convergent adaptation
Authors: Lee Kristin M. , Coop Graham
Published: June 2019

Convergent adaptation is the independent evolution of similar traits conferring a fitness advantage in two or more lineages. Cases of convergent adaptation inform our ideas about the ecological and molecular basis of adaptation. In judging the degree to which putative cases of convergent adaptation provide an independent replication of the process of adaptation, it is necessary to establish the degree to which the evolutionary change is unexpected under null models and to show that selection has repeatedly, independently driven these changes. Here, we discuss the issues that arise from these questions particularly for closely related populations, where gene flow and standing variation add additional layers of complexity. We outline a conceptual framework to guide intuition as to the extent to which evolutionary change represents the independent gain of information owing to selection and show that this is a measure of how surprised we should be by convergence. Additionally, we summarize the ways population and quantitative genetics and genomics may help us address questions related to convergent adaptation, as well as open new questions and avenues of research.

This article is part of the theme issue ‘Convergent evolution in the genomics era: new insights and directions’.
Ecological factors and morphological traits are associated with repeated genomic differentiation between lake and stream stickleback
Authors: Rennison Diana J. , Stuart Yoel E. , Bolnick Daniel I. , Peichel Catherine L.
Published: June 2019

The repeated evolution of similar phenotypes in independent populations (i.e. parallel or convergent evolution) provides an opportunity to identify genetic and ecological factors that influence the process of adaptation. Threespine stickleback fish (Gasterosteus aculeatus) are an excellent model for such studies, as they have repeatedly adapted to divergent habitats across the Northern hemisphere. Here, we use genomic, ecological and morphological data from 16 independent pairs of stickleback populations adapted to divergent lake and stream habitats. We combine a population genomic approach to identify regions of the genome that are likely under selection in these divergent habitats with an association mapping approach to identify regions of the genome that underlie variation in ecological factors and morphological traits. Over 37% of genomic windows are repeatedly differentiated across lake–stream pairs. Similarly, many genomic windows are associated with variation in abiotic factors, diet items and morphological phenotypes. Both the highly differentiated windows and candidate trait windows are non-randomly distributed across the genome and show some overlap. However, the overlap is not significant on a genome-wide scale. Together, our data suggest that adaptation to divergent food resources and predation regimes are drivers of differentiation in lake–stream stickleback, but that additional ecological factors are also important.

This article is part of the theme issue ‘Convergent evolution in the genomics era: new insights and directions’.
Parallelism and convergence in post-domestication adaptation in cereal grasses
Authors: Woodhouse M. R. , Hufford M. B.
Published: June 2019

The selection of desirable traits in crops during domestication has been well studied. Many crops share a suite of modified phenotypic characteristics collectively known as the domestication syndrome. In this sense, crops have convergently evolved. Previous work has demonstrated that, at least in some instances, convergence for domestication traits has been achieved through parallel molecular means. However, both demography and selection during domestication may have placed limits on evolutionary potential and reduced opportunities for convergent adaptation during post-domestication migration to new environments. Here we review current knowledge regarding trait convergence in the cereal grasses and consider whether the complexity and dynamism of cereal genomes (e.g., transposable elements, polyploidy, genome size) helped these species overcome potential limitations owing to domestication and achieve broad subsequent adaptation, in many cases through parallel means.

This article is part of the theme issue ‘Convergent evolution in the genomics era: new insights and directions’.
Integrating natural history collections and comparative genomics to study the genetic architecture of convergent evolution
Authors: Lamichhaney Sangeet , Card Daren C. , Grayson Phil , Tonini João F. R. , Bravo Gustavo A. , Näpflin Kathrin , Termignoni-Garcia Flavia , Torres Christopher , Burbrink Frank , Clarke Julia A. , Sackton Timothy B. , Edwards Scott V.
Published: June 2019

Evolutionary convergence has been long considered primary evidence of adaptation driven by natural selection and provides opportunities to explore evolutionary repeatability and predictability. In recent years, there has been increased interest in exploring the genetic mechanisms underlying convergent evolution, in part, owing to the advent of genomic techniques. However, the current ‘genomics gold rush’ in studies of convergence has overshadowed the reality that most trait classifications are quite broadly defined, resulting in incomplete or potentially biased interpretations of results. Genomic studies of convergence would be greatly improved by integrating deep ‘vertical’, natural history knowledge with ‘horizontal’ knowledge focusing on the breadth of taxonomic diversity. Natural history collections have and continue to be best positioned for increasing our comprehensive understanding of phenotypic diversity, with modern practices of digitization and databasing of morphological traits providing exciting improvements in our ability to evaluate the degree of morphological convergence. Combining more detailed phenotypic data with the well-established field of genomics will enable scientists to make progress on an important goal in biology: to understand the degree to which genetic or molecular convergence is associated with phenotypic convergence. Although the fields of comparative biology or comparative genomics alone can separately reveal important insights into convergent evolution, here we suggest that the synergistic and complementary roles of natural history collection-derived phenomic data and comparative genomics methods can be particularly powerful in together elucidating the genomic basis of convergent evolution among higher taxa.

This article is part of the theme issue ‘Convergent evolution in the genomics era: new insights and directions’.
Limits in the detection of m6A changes using MeRIP/m6A-seq
Authors: McIntyre Alexa B.R. , Gokhale Nandan S. , Cerchietti Leandro , Jaffrey Samie R. , Horner Stacy M. , Mason Christopher E.
Published: June 2019

Many cellular mRNAs contain the modified base m6A, and recent studies have suggested that various stimuli can lead to changes in m6A. The most common method to map m6A and to predict changes in m6A between conditions is methylated RNA immunoprecipitation sequencing (MeRIP-seq), through which methylated regions are detected as peaks in transcript coverage from immunoprecipitated RNA relative to input RNA. Here, we generated replicate controls and reanalyzed published MeRIP-seq data to estimate reproducibility across experiments. We found that m6A peak overlap in mRNAs varies from ∼30 to 60% between studies, even in the same cell type. We then assessed statistical methods to detect changes in m6A peaks as distinct from changes in gene expression. However, from these published data sets, we detected few changes under most conditions and were unable to detect consistent changes across studies of similar stimuli. Overall, our work identifies limits to MeRIP-seq reproducibility in the detection both of peaks and of peak changes and proposes improved approaches for analysis of peak changes.
Arabidopsis SWR1-associated protein methyl-CpG-binding domain 9 is required for histone H2A.Z deposition
Authors: Potok Magdalena E. , Wang Yafei , Xu Linhao , Zhong Zhenhui , Liu Wanlu , Feng Suhua , Naranbaatar Bilguudei , Rayatpisheh Shima , Wang Zonghua , Wohlschlegel James A. , Ausin Israel , Jacobsen Steven E.
Published: June 2019

Deposition of the histone variant H2A.Z by the SWI2/SNF2-Related 1 chromatin remodeling complex (SWR1-C) is important for gene regulation in eukaryotes, but the composition of the Arabidopsis SWR1-C has not been thoroughly characterized. Here identify interacting partners of a conserved Arabidopsis SWR1 subunit, ACTIN-RELATED PROTEIN 6 (ARP6). We isolated nine predicted components, and identified additional interactors implicated in histone acetylation and chromatin biology. One of the novel interacting partners, methyl-CpG-binding domain 9 (MBD9), also strongly interacted with the Imitation SWItch (ISWI) chromatin remodeling complex. MBD9 was required for deposition of H2A.Z at a distinct subset of ARP6-dependent loci. MBD9 was preferentially bound to nucleosome-depleted regions at the 5’ ends of genes containing high levels of activating histone marks. These data suggest that MBD9 is a SWR1-C interacting protein required for H2A.Z deposition at a subset of actively transcribing genes.
Metastable neural dynamics underlies cognitive performance across multiple behavioural paradigms
Authors: Alderson Thomas H. , Bokde Arun L.W. , Kelso J.A.Scott. , Maguire Liam , Coyle Damien
Published: June 2019

Despite resting state networks being associated with a variety of cognitive abilities, it remains unclear how these local areas act in concert to express particular cognitive operations. Theoretical and empirical accounts indicate that large-scale resting state networks reconcile dual tendencies toward integration and segregation by operating in a metastable regime of their coordination dynamics. One proposal is that metastability confers important behavioural qualities by dynamically binding distributed local areas into large-scale neurocognitive entities. We tested this hypothesis by analysing fMRI data in a large cohort of healthy individuals (N=566) and comparing the metastability of the brain’s large-scale resting network architecture at rest and during the performance of several tasks. Task-based reasoning was principally characterised by high metastability in cognitive control networks and low metastability in sensory processing areas. Although metastability between resting state networks increased during task performance, cognitive ability was more closely linked to spontaneous activity. High metastability in the intrinsic connectivity of cognitive control networks was linked to novel problem solving (or fluid intelligence) but was less important in tasks relying on prior experience (or crystallised intelligence). Crucially, subjects with resting architectures similar or ‘pre-configured’ to a task-general arrangement demonstrated superior cognitive performance. Taken together, our findings support a critical linkage between the spontaneous metastability of the large-scale networks of the cerebral cortex and cognition.