bluuebunny/crossref_metadata_2025 huggingface dataset:
Assessment of the reliability and reproducibility of the Langenskiöld classification in Blount’s disease
Authors: du Plessis Jason , Firth Gregory B. , Robertson Anthony
Published: November 2019

The Langenskiöld classification is the most commonly utilized classification system for the radiological features of Blount’s disease. Although there is only a single study found on the interobserver variability and none found on the intraobserver variability, it is commonly used for prognostication and guiding management decisions. The aim of this study was to determine the reliability and reproducibility of the Langenskiöld classification. A retrospective review of radiographs was done of patients treated for infantile and juvenile Blount’s disease at Chris Hani Baragwanath Academic Hospital from 2006 to 2016. There were 70 radiographs of acceptable quality, which were reviewed and staged on two occasions according to the Langenskiöld classification by three orthopaedic consultants and three orthopaedic surgery senior residents. Pearson correlation coefficients, percentage agreements, and κ statistics were used to evaluate both the reliability and reproducibility. Of the 70 images staged, only two (2.9%) were staged the same by all six observers, and 20 (28.6%) images differed by a single stage. The consultants had 17 (24.3%) images staged the same whereas the residents had 12 (17.1%) images staged the same. The overall κ for all six observers showed a fair agreement of 0.24. Again, the consultants had a higher κ-value compared to residents of 0.25 and 0.24, respectively. The reproducibility amongst all observers was fair with a κ-value of 0.38. The consultants had a higher mean score of 0.48 compared to 0.26 for the residents. There was only a fair overall reliability and reproducibility amongst the six observers. We recommend the Langenskiöld classification be used with caution when being used for prognostication and management planning as well as when interpreting any research relying on this classification. Level of evidence: Level III, diagnostic study.
Procalcitonin and Neutrophil Lymphocyte Ratio After Spinal Instrumentation Surgery
Authors: Inose Hiroyuki , Kobayashi Yutaka , Yuasa Masato , Hirai Takashi , Yoshii Toshitaka , Okawa Atsushi
Published: November 2019

Study Design.

This was a retrospective observational study.

Objective.

To assess the diagnostic value of procalcitonin (PCT) and neutrophil lymphocyte ratio (NLR) for predicting surgical site infection (SSI) in patients undergoing spinal instrumentation surgery, we analyzed a large consecutive cohort of patients who had undergone spinal instrumentation surgery.

Summary of Background Data.

Although PCT and NLR are commonly used as markers for bacterial infection, the diagnostic value of these factors for predicting SSI in the context of spinal instrumentation surgery has not been extensively investigated.

Methods.

We retrospectively investigated 242 patients who underwent spinal instrumentation surgery and evaluated the significance of various postoperative measures for predicting SSI, including PCT and NLR. We then determined the diagnostic cut-off values for these markers in the prediction of SSI using receiver operating characteristic curve analysis.

Results.

Among the 242 patients analyzed, 10 were diagnosed with infection. Even though univariate analysis showed that neutrophil percentage and NLR at 6 to 7 days postoperatively were significant predictors for SSI, PCT at 6 to 7 days postoperatively did not differ significantly between the SSI and non-SSI groups. The cut-off value used for neutrophil percentage at 6 to 7 days postoperatively was more than 69.0% [sensitivity, 80.0%; specificity, 70.0%; area under the curve, 0.737]. The cut-off value used for NLR at 6 to 7 days postoperatively was 3.87 (sensitivity, 70.0%; specificity, 73.2%; area under the curve, 0.688).

Conclusion.

Neutrophil percentage and NLR at 6 to 7 days postoperatively were more useful markers than PCT at 6 to 7 days postoperatively for early prediction of SSI in patients who had undergone spinal instrumentation surgery. Therefore, routine use of PCT as a predictor of postoperative infection is not supported by the results of this study.

Level of Evidence: 4
Complications with Minimally Invasive Transforaminal Lumbar Interbody Fusion for Degenerative Spondylolisthesis in the Obese Population
Authors: Buyuk Abdul Fettah , Shafa Eiman , Dawson John M. , Schwender James D.
Published: November 2019

Study Design.

A level-3 retrospective cohort analysis.

Objective.

The aim of this study was to describe obesity's effect on complications and outcomes in degenerative spondylolisthesis patients treated by minimally invasive transforaminal lumbar interbody fusion (MI TLIF).

Summary of Background Data.

Obesity is associated with a greater complication rate among lumbar spine surgery patients. Poor clinical outcomes might likewise be supposed, but the association is not well established. Minimally invasive techniques have been developed to reduce complications and improve clinical outcomes in comparison to traditional open techniques.

Methods.

We reviewed 134 consecutive patients with degenerative spondylolisthesis undergoing MI TLIF. Subjects were grouped into nonobese (N = 65) and obese (N = 69) cohorts. The obese group was further subdivided by BMI. Patient demographics, perioperative complications, and outcome scores were collected over a minimum of 24 months. Four periods (intraoperative, postoperative hospitalization, 6-month, and 24-month postoperative) were assessed.

Results.

Cohort demographics were not significantly different, but it was noted that obese patients had more major comorbidities than nonobese patients. There was no difference in intraoperative complications between the two groups. The in-hospital complication rate was significantly greater in the obese group. The 6-month postoperative complication rate was not different between cohorts. Wound drainage was most common and noted only in the obese cohort. Complications at 24 months were not different but did trend toward significance in the obese for recurrence of symptoms and total complications. Functional outcome was better among nonobese subjects compared with obese subjects at every interval (significant at 6 and 12 months). Back pain scores were significantly better among nonobese subjects than obese subjects at 24 months, but Leg Pain scores were not different.

Conclusions.

MI TLIF can be safely performed in the obese population despite a higher in-hospital complication rate. Knowledge of common complications will help the treatment team appropriately manage obese patients with degenerative spondylolisthesis.

Level of Evidence:3
Simulation-Based Team Leadership Training Improves Team Leadership During Actual Trauma Resuscitations: A Randomized Controlled Trial
Authors: Fernandez Rosemarie , Rosenman Elizabeth D. , Olenick Jeffrey , Misisco Anthony , Brolliar Sarah M. , Chipman Anne K. , Vrablik Marie C. , Kalynych Colleen , Arbabi Saman , Nichol Graham , Grand James , Kozlowski Steve W. J. , Chao Georgia T.
Published: November 2019

Objectives:

Trauma resuscitations are complex critical care events that present patient safety-related risk. Simulation-based leadership training is thought to improve trauma care; however, there is no robust evidence supporting the impact of leadership training on clinical performance. The objective of this study was to assess the clinical impact of simulation-based leadership training on team leadership and patient care during actual trauma resuscitations.

Design:

Randomized controlled trial.

Setting:

Harborview Medical Center (level 1 trauma center).

Subjects:

Seventy-nine second- and third-year residents were randomized and 360 resuscitations were analyzed.

Interventions:

Subjects were randomized to a 4-hour simulation-based leadership training (intervention) or standard orientation (control) condition.

Measurements and Main Results:

Participant-led actual trauma resuscitations were video recorded and coded for leadership behaviors and patient care. We used random coefficient modeling to account for the nesting effect of multiple observations within residents and to test for post-training group differences in leadership behaviors while controlling for pre-training behaviors, Injury Severity Score, postgraduate training year, and days since training occurred. Sixty participants completed the study. There was a significant difference in post-training leadership behaviors between the intervention and control conditions (b1 = 4.06, t (55) = 6.11, p < 0.001; intervention M = 11.29, se = 0.66, 95% CI, 9.99–12.59 vs control M = 7.23, se = 0.46, 95% CI, 6.33–8.13, d = 0.92). Although patient care was similar between conditions (b = 2.00, t (55) = 0.99, p = 0.325; predicted means intervention M = 62.38, se = 2.01, 95% CI, 58.43–66.33 vs control M = 60.38, se = 1.37, 95% CI, 57.69–63.07, d = 0.15), a test of the mediation effect between training and patient care suggests leadership behaviors mediate an effect of training on patient care with a significant indirect effect (b = 3.44, 95% CI, 1.43–5.80). Across all trauma resuscitations leadership was significantly related to patient care (b1 = 0.61, se = 0.15, t (273) = 3.64, p < 0.001).

Conclusions:

Leadership training resulted in the transfer of complex skills to the clinical environment and may have an indirect effect on patient care through better team leadership.
Conditional Survival With Increasing Duration of ICU Admission: An Observational Study of Three Intensive Care Databases
Authors: Marshall Dominic C. , Hatch Robert A. , Gerry Stephen , Young J. Duncan , Watkinson Peter
Published: November 2019

Objectives:

Prolonged admissions to an ICU are associated with high resource utilization and personal cost to the patient. Previous reports suggest increasing length of stay may be associated with poor outcomes. Conditional survival represents the probability of future survival after a defined period of treatment on an ICU providing a description of how prognosis evolves over time. Our objective was to describe conditional survival as length of ICU stay increased.

Design:

Retrospective observational cohort study of three large intensive care databases.

Setting:

Three intensive care databases, two in the United States (Medical Information Mart for Intensive Care III and electronic ICU) and one in United Kingdom (Post Intensive Care Risk-Adjusted Alerting and Monitoring).

Patients:

Index admissions to intensive care for patients 18 years or older.

Interventions:

None.

Measurements and Main Results:

A total of 11,648, 38,532, and 165,125 index admissions were analyzed from Post Intensive Care Risk-Adjusted Alerting and Monitoring, Medical Information Mart for Intensive Care III and electronic ICU databases respectively. In all three cohorts, conditional survival declined over the first 5–10 days after ICU admission and changed little thereafter. In patients greater than or equal to 75 years old conditional survival continued to decline with increasing length of stay.

Conclusions:

After an initial period of 5–10 days, probability of future survival does not decrease with increasing length of stay in unselected patients admitted to ICUs. These findings were consistent between the three populations and suggest that a prolonged admission to an ICU is not a reason for a pessimism in younger patients but may indicate a poor prognosis in the older population.
An Updated Healthcare System-Wide Clinical Pathway for Managing Patients With Chest Pain and Acute Coronary Syndromes
Authors: Brener Michael I. , Tung Jen , Stant Jennifer , Sayan Osman R. , Suh Edward H. , Minutello Robert M. , Sharma Rahul , Brener Sorin J. , Melniker Lawrence A. , Moustakakis Emmanuel N. , Neuberg Gerald , Breen Lorna M. , Nutovits Ronald , Kats Yuliya , Amaranto Andrew , Pucillo Anthony , Kirtane Ajay J. , Rabbani LeRoy E.
Published: November 2019

Clinical pathways reinforce best practices and help healthcare institutions standardize care delivery. The NewYork-Presbyterian/Columbia University Irving Medical Center has used such a pathway for the management of patients with chest pain and acute coronary syndromes for almost 2 decades. A multidisciplinary panel of stakeholders serially updates the algorithm according to new data and recently published guidelines. Herein, we present the 2019 version of the clinical pathway. We explain the rationale for changes to the algorithm and describe our experience expanding the pathway to all the 8 affiliated institutions within the NewYork Presbyterian healthcare system.
A Novel Use of Prehospital Telemedicine to Decrease Door to Computed Tomography Results in Acute Strokes
Authors: Bilotta Mary , Sigal Adam P. , Shah Ankit , Martin Anthony , Schlappy David A. , Sorensen Greg , Barbera Charles
Published: November 2019

Introduction:

Timely emergency department (ED) recognition of acute strokes reduces morbidity and mortality and improves outcomes. Prehospital telehealth evaluation rapidly assesses patients with stroke symptoms and mobilizes resources before ED arrival, decreasing ED arrival to computed tomography (CT) result times. Expediting CT results reduces the decision time to determining thrombolytic therapy eligibility.

Methods:

Seventeen ambulances in our region were supplied with equipment to perform a nonrecordable video examination with an ED physician. Emergency Medical Service requested a physician video examination on patients with a positive prehospital Cincinnati Stroke Scale. The physician and paramedic conducted an NIH-8 scale, and, based on the assessment, the patients were placed directly on the CT scanner table.

Results:

Four time intervals that impact CT acquisition and thrombolytic decision-making were measured. There was improvement in all time intervals. Time from ED arrival to CT order decreased 1.7 minutes. Time from arrival to study start decreased 5.7 minutes. Time from CT order to result decreased 3.89 minutes and time from ED arrival to CT result decreased 5.6 minutes.

Discussion:

Prehospital telehealth consults with paramedics, and the receiving hospital for acute strokes significantly decreased times for all metrics studied including the time from ED arrival to CT result.
Effects of core stability exercise for patients with neck pain
Authors: He Yikang , Sun Wudong , Zhao Xianghu , Ma Ming , Zheng Zengbin , Xu Liang
Published: November 2019

Background:

Neck pain is an important cause of disability. In spite of its high prevalence rate, treatment of the disorder is a challenging topic. Exercise therapy appears to be effective at decreasing pain and improving function for patients with NP in practice guidelines. Core stability exercise is becoming increasingly popular for NP. However, it is currently unknown whether core stability exercise produces more beneficial effects than general exercise in patients with NP. The aim of this study is to explore the therapeutic effect of core stability exercise for neck pain.

Methods:

This review will only include randomized controlled trials (RCTs). Published articles from July 2009 to July 2019 will be identified using electronic searches. Search strategy will be performed in 3 English databases, 1 Chinese database, and the WHO International Clinical Trials Registry Platform. Two reviewers will screen, select studies, extract data, and assess quality independently. The methodological quality including the risk of bias of the included studies will be evaluated using a modified assessment form, which is based on Cochrane assessment tool and Physiotherapy Evidence Database scale. Review Manager Software (Revman5.3) will be used for heterogeneity assessment, generating funnel-plots, data synthesis, subgroup analysis, and sensitivity analysis. We will use GRADE system to evaluate the quality of our evidence.

Results:

We will provide some more practical and targeted results investigating the effect of Core Stability Exercise (CSE) for Neck Pain (NP) in the current meta-analysis. Meanwhile, we will ascertain study progress of Core Stability Exercise for Neck Pain and find out defects or inadequacies of previous studies, so that future researchers could get beneficial guidance for more rigorous study.

Conclusion:

The stronger evidence about Neck Pain's rehabilitative effect and safety will be provided for clinicians and policymakers.

Systematic review registration:

PROSPERO CRD42017055711.

Ethics and dissemination:

We do not apply for formal ethical approval from ethics committee because all of the study data in our review will be obtained in an anonymous way. Findings of this study are projected to be disseminated through peer-review publications.
Decompression with fusion is not in superiority to decompression alone in lumbar stenosis based on randomized controlled trials
Authors: Xu Shuai , Wang Jinyu , Liang Yan , Zhu Zhenqi , Wang Kaifeng , Qian Yalong , Liu Haiying
Published: November 2019

Background:

Although some studies had been published, it was more controversial on the superiority of decompression alone (D) and decompression with fusion (F) for the treatment of lumbar spinal stenosis (LSS) recently, especially newest articles with different opinions. A meta-analysis was performed to compare efficacy on D and F for LSS regardless of degenerative spondylolisthesis (DS) with randomized controlled trials (RCTs).

Methods:

The databases include PUBMED/MEDLINE, EMBASE, Cochrane Library, and Web of Science from January 1970 to December 2018. The information of screened studies included demographics, clinical outcomes, and secondary measures, then data synthesis and meta-analysis were progressed. Subgroup analysis was stratified by DS and follow-up time (36 months). Continuous variables and dichotomous variables were respectively reported as weighted mean difference and odds ratios (ORs). The strength of evidence was evaluated by the grades of recommendation, assessment, development, and evaluation (GRADE) system.

Results:

Nine RCTs met inclusion criteria with a total of 857 patients (367 were in D group and 490 were in F group). There were no statistical difference in visual analog scale changes on back and leg pain between D and F group (mean difference [MD] = −0.03, 95% confidence interval [CI] [–0.38, 0.76], z = 0.08, P = .94; MD = 0.11, 95% CI [–1.08, 1.30], z = 0.18, P = .86, respectively); patients’ satisfaction was of no difference between the 2 groups, together with the change of the Oswestry disability index and European quality of life-5 dimensions (P > .05). There were no difference in the rate of complication (P = .50) and reoperation (P = .11) while a statistical significance of longer operation duration (P < .0001), more blood loss (P = .004) but amazing lower rate of adjacent segment degenerative/disease (ASD) (OR = 2.35, P = .02) in F group. The subgroup analysis on DS showed that basically all measures were in consistency with meta-analysis. There was a higher reoperation rate in middle-to-long term (>36 months) in D group and ASD was the most seasons of reoperation no matter the follow-up time. According to the GRADE system, the grade of this meta-analysis was of “High” quality.

Conclusion:

F group has no better clinical results than D alone in LSS, regardless of DS and follow-up. The conclusion is of “High” quality and the grade strength of recommendation was “Strong.”
Nomogram predicting overall survival of rectal squamous cell carcinomas patients based on the SEER database
Authors: Diao Jian-Dong , Wu Chun-Jiao , Cui Hong-Xia , Bu Ming-Wei , Yue Dan , Wang Xue , Liu Yan-Ling , Yang Yong-Jing
Published: November 2019

We aimed to evaluate the prognostic value of clinical and pathologic factors in rectal squamous cell carcinomas (SCC) and to construct a nomogram for their outcome prediction.

The study cohort was selected from Surveillance, Epidemiology, and End Results (SEER) program between January 2004 and December 2013. Univariate and multivariate analyses were performed using Cox proportional hazards regression model to evaluate the prognostic value of involved variables. All prognostic factors were combined to construct a nomogram to predict the overall survival (OS), followed by discrimination as well as calibration plots and receiver operating characteristic (ROC) curves for assessing the predictive accuracy of the nomogram.

We identified 806 patients with a median follow-up time of 35 months. Multivariate analyses revealed that marital status (P < .001), age (P < .001), T stage (P = .008), M stage (P < .001), surgery (P = .004), chemotherapy (P = .003) and radiotherapy (P = .016) were independent prognostic factors of OS. Finally, the 7 variables were combined to construct a 3-year and 5-year OS nomogram. The concordance indexes (C-indexes) of OS were 0.756 (95% CI, 0.726–0.786) for the internal validation and 0.729 (95% CI, 0.678–0.780) for the external validation. Additionally, there was superior discrimination power of the nomogram over the SEER stage or the 8th edition AJCC TNM staging classification (P < .001). Calibration plots further showed good consistency between the nomogram prediction and actual observation. The area under the curve (AUC) of ROC curves for 3-year OS was 0.811 (95% CI: 0.769–0.853) in the training cohort and 0.748 (95% CI: 0.681–0.815) in the validation cohort. The AUC for 5-year OS was 0.770 (95% CI: 0.721–0.819) in the training cohort and 0.797 (95% CI: 0.731–0.863) in the validation cohort. Finally, Kaplan-Meier analysis further validates the predictive potential of the nomogram.

Marital status, age, T stage, M stage, surgery, chemotherapy and radiotherapy were significantly associated with OS of patients with rectal SCC. This predictive model has the potential to provide an individualized risk estimate of survival in patients with rectal SCC.
Does nonexistent of your hands on the screen guarantee no radiation exposure to your body? – Study on exposure of the practitioner's hands to radiation during C-arm fluoroscopy-guided injections and effectiveness of a new shielding device
Authors: Lee Jae-Eun , Kim Ju-Hyun , Lee Su-Jin , Kim Mingeon , Nam Tae-Woo , Kim Chul Hyun , Jung Tae-Du , Hwang Jong-Moon
Published: November 2019

Observational phantom study.

This study aimed to evaluate the radiation exposure dose of practitioner's hands when performing C-arm guided procedures and to determine the usefulness of our newly designed radiation shielding device.

C-arm guided procedures including lumbar transforaminal epidural steroid injections (TFESIs) are commonly used for pain control induced by lumbar radiculopathy. The practitioner's hands are vulnerable to radiation exposure because of the long exposure time and short distance from the radiation resource. No studies to date have reported the cumulative exposure of the physician's hands according to location and exposure time.

Using a chest phantom irradiated with X-rays under lumbar TFESI conditions, cumulative scatter radiation dose was measured at 36 points using a dosimeter. The measurements were checked at 1, 3, 5, 10 minutes of radiation exposure. The experiment was repeated using our newly designed shielding device.

Significant radiation accumulation was observed in the field where the practitioner's hands might be placed during C-arm guided procedures. The further the distance from the radiation resource and the shorter the exposure time, the smaller was the cumulative radiation expose dose. The new shielding device showed an excellent shielding rate (66.0%–99.9%) when the dosimeter was within the shielding range. However, at some points, increased accumulated radiation exposure dose was observed, although the dosimeter was within the range of the shielding device.

To reduce radiation exposure of the practitioner's hands when performing C-arm-guided procedures, the radiation exposure time should be decreased and a greater distance from the radiation resource should be maintained. When using our shielding device, placing the hand close to the device surface and minimizing the time using fluoroscopy minimized the radiation exposure of the hand.
Impact of physical exercise on children with attention deficit hyperactivity disorders
Authors: Zang Yu
Published: November 2019

Background:

Attention deficit hyperactivity disorder (ADHD) which is characterized by developmentally inappropriate levels of attention, hyperactivity and impulsivity, is considered as the most common neurodevelopmental disorder in childhood. Physical exercise has shown to have several benefits in the improvement of children with ADHD. In this meta-analysis, we aimed to systematically show, with evidence, the impact of physical exercise on children with ADHD.

Methods:

Web of Science, MEDLINE, EMBASE, Google Scholar, Cochrane Central and http://www.ClinicalTrials.gov were the searched sources for studies which were based on the impact of physical exercise on children with ADHD. Relevant endpoints were assessed. This evidence based meta-analysis was carried out by the most relevant RevMan 5.3 software. Due to the involvement of continuous data (mean and standard deviation), weight mean difference (WMD) with 95% confidence intervals (CI) were used to represent the final analysis. A significant level ofP≤ .05 was set and a fixed statistical effect model was used throughout the analysis.

Results:

Fourteen studies with a total number of 574 participants with ADHD were included in this evidenced based meta-analysis. Two hundred and seventy six (276) participants were assigned to the physical activity group whereas 298 participants were assigned to the control group. Results of this analysis showed that anxiety and depression were significantly improved with physical activity in these children with ADHD (WMD: -1.84; 95% CI: [-2.65 – (-1.03)],P = .00001). Hyperactive/impulsive symptoms (WMD: -0.01; 95% CI: [-0.32 – 0.29],P = .93) and inattention symptoms (WMD: -0.22; 95% CI: [-0.51 – 0.08],P = .15) were also improved with physical exercise but the results were not statistically significant. This evidence based analysis showed thought problems (WMD: -3.49; 95% CI: [-5.51 – (-1.47)],P = .0007), social problems (WMD: -5.08; 95% CI: [-7.34 – (-2.82)],P = .0001), and aggressive behaviors (WMD: -3.90; 95% CI: [-7.10 – (-0.70)],P = .02) to have significantly been improved in participants with ADHD who were assigned to physical activity group.

Conclusions:

This current meta-analysis showed with evidence, that physical exercise has a major contribution owing to significant improvement in anxiety and depression, aggressive behaviors, thought and social problems among children suffering from ADHD. Therefore, physical exercise should be incorporated in the daily life of children with ADHD. Further future research should be able to confirm this hypothesis.
Evidence of the Linkage Between Hospital-based Care Coordination Strategies and Hospital Overall (Star) Ratings
Authors: Benjenk Ivy , Franzini Luisa , Chen Jie
Published: November 2019

Background:

In the new era of value-based payment models and pay for performance, hospitals are in search of the silver bullet strategy or bundle of strategies capable of improving their performance on quality measures.

Objectives:

To determine whether there is an association between adoption of hospital-based care coordination strategies and Centers for Medicare and Medicaid Services overall hospital quality (star) ratings and readmission rates.

Research Design:

We used survey data from the American Hospital Association (AHA) and categorized respondents by the number of care coordination strategies that they reported having widely implemented. We used multiple logistic regression models to examine the association between the number of strategies and hospital overall rating performance and disease-specific 30-day excess readmission ratios, while controlling for hospital and county characteristics and state-fixed effects.

Subjects:

A total of 710 general acute care noncritical access hospitals that received star ratings and responded to the 2015 AHA Care Systems and Payment Survey.

Measures:

Centers for Medicare and Medicaid Services overall hospital ratings, 30-day excess readmission ratios.

Results:

As compared with hospitals with 0–2 strategies, hospitals with 3 to 4 strategies (P=0.007), 5–7 strategies (P=0.002), or 8–12 strategies (P=0.002) had approximately 2.5× the odds of receiving a top rating (4 or 5 stars). Care coordination strategies were positively associated with lower 30-day readmission ratios for patients with chronic medical conditions, but not for surgical patients. Medication reconciliation, visit summaries, outreach after discharge, discharge care plans, and disease management programs were each individually associated with top ratings.

Conclusions:

Care coordination strategies are associated with high overall hospital ratings.
Quality of Life and Pain Experienced by Children and Adolescents With Cancer at Home Following Discharge From the Hospital
Authors: Duran Joana , Bravo Lilian , Torres Vanessa , Craig Alexandra , Heidari Jasmine , Adlard Kathleen , Secola Rita , Granados Renee , Jacob Eufemia
Published: November 2019

An exploratory study was conducted to examine the quality of life and pain experienced by patients with pediatric cancer at home after discharge. Physical, cognitive, social, and emotional aspects of quality of life were measured and how these may be affected by age, sex, diagnosis, and pain status. The authors also characterized intensity, location, and quality of pain experienced. A sample of 33 patients participating in a larger study was selected on the basis of having pain on the day of discharge and having completed the Pediatric Quality of Life Inventory Generic, Cancer Module, Multidimensional Fatigue Scale, and the Adolescent Pediatric Pain Tool at home. Cancer diagnoses were leukemias/lymphomas (42.4%), brain/central nervous system tumors (27.3%), sarcomas (24.2%), or other (6.1%). More than half of patients reported pain (n=17; 51.5%). Patients with pain had more fatigue affecting the quality of life (P=0.01), and lower physical and emotional functioning, leading to lower overall health-related quality of life scores (P=0.011). Female individuals and adolescents reported worse emotional functioning (P=0.02 and P=0.05, respectively). Physical, cognitive, and social functioning were lowest among patients diagnosed with sarcomas (P=0.00, P=0.01, and P=0.04, respectively). It is important to understand the symptom experience of patients at home as a first step in moving towards optimal discharge teaching and treatment.
A Leadership Opportunity
Authors: VandeWaa Elizabeth A. , Turnipseed David L. , Lawrence Sherry
Published: November 2019

Despite the availability of the political process, it has not been used optimally by nurses to improve negative issues facing the profession. This study indicates that nurses are generally not astute regarding the political process and are not significantly involved. Nurse leaders have an opportunity to educate and motivate nurses to be formidable participants in the political process, champion the healthcare agenda, and propound policy efforts to improve patient care and the nursing profession.
Mesonephric-like Carcinoma of the Endometrium
Authors: Euscher Elizabeth D. , Bassett Roland , Duose Dzifa Y. , Lan Chieh , Wistuba Ignacio , Ramondetta Lois , Ramalingam Preetha , Malpica Anais
Published: November 2019

Endometrial mesonephric-like carcinomas (MLCa) are uncommon with <50 reported cases thus far. Previous studies have characterized the histologic, immunohistochemical, and molecular features of MLCa; however, there is limited information with respect to outcome. This single-institution study of 23 uterine MLCas characterizes the behavior of such a neoplasm. Uterine MLCas (2004-present) had review of histologic features, immunohistochemical results, molecular profile, and clinical information (stage, treatment, follow-up). The behavior of MLCa was compared with low-grade endometrioid carcinomas (ECas) and uterine serous carcinomas (USCs) treated at our institution from 2004 to present. All MLCas had a mixture of previously described architectural and cytologic features most notably ductal and/or tubular architecture (21/23), nuclei resembling those of papillary thyroid carcinoma (18/23), and at least focal intraluminal eosinophilic secretions (20/23). Immunoperoxidase studies facilitated diagnosis in 22 cases: CD10, 10/10; calretinin, 5/15; estrogen receptor (≥10% nuclei), 6/21; progesterone receptor, 1/15; GATA-3, 15/16; TTF-1, 11/16. Fourteen of 17 tested cases had a KRAS mutation (7 as the only alteration; 7 with additional mutations including PIK [n=5]; PTEN [n=2], CTNNB1 [n=1]).One case had mutations in PTEN, PIK, and CTNNB1 without KRAS; 2 cases had no detectable somatic mutation. Overall, 48% of patients presented with International Federation of Gynecology and Obstetrics (FIGO) stage 3 or 4 disease with the following uterine risk factors: >50% myometrial invasion, 20/23; lymphovascular space invasion, 16/23; cervical stromal invasion, 7/23. Twenty patients had adjuvant therapy (7 radiation only; 13 chemotherapy±radiation), whereas 3 patients had either unknown or declined therapy. Follow-up was known for 21 patients: 17 patients had recurrences or never achieved remission with the lung being the most common recurrence site (n=9); 7 patients died of disease. The median progression-free survival was 18.2 months for MLCa compared with 183 months for ECa and 67.1 months for USC. The median overall survival for MLCa was 70.6 months compared with 139.1 months for USC (median survival for ECa not reached). Uterine MLCa is uncommon with most tumors recognized by architectural heterogeneity, vesicular, overlapping nuclei with grooves, and eosinophilic luminal secretions. The typical immunoprofile includes low to absent expression of hormone receptors but at least focal expression of GATA-3 and/or TTF-1. Most tested cases had a KRAS mutation although genetic mutations typically associated with ECa are not uncommon. Compared with more commonly encountered types of ECa, MLCa is more aggressive with a tendency towards earlier and distant recurrence.
Long-Term Outcomes of the Minimal Skin Incision Technique for Correcting Severe Microform and Minor-Form Cleft Lip With Philtrum Reconstruction Through the Intraoral Incision
Authors: Cho Byung Chae , Kim Yun Hyun , Tian Lulu , Lee Joon Seok , Lee Jeong Woo , Choi Kang Young , Yang Jung Dug , Chung Ho Yun
Published: November 2019

Background:

Because the traditional technique is known to cause visible scarring, it is challenging to yield optimal outcomes while treating a severe type of microform and minor-form cleft lip. The authors present a new refined technique with minimal skin incision and philtrum formation through an intraoral incision.

Methods:

The surgical technique involves single Z-plasty or double or triple unilimb Z-plasty to restore an elevated cupid's bow peak and overlapping of an orbicularis oris muscle flap to create the philtrum through an intraoral incision. Cleft lip nasal deformity was corrected with reverse-U incision and V-Y plasty.

Results:

Eighteen patients were operated between September 2008 and June 2017. Patient age at the time of surgery ranged from 3 to 12 months. The duration of follow-up ranged from 12 months to 7 years (mean, 36 months). The elevated cupid's bow was corrected by performing single Z-plasty in 6 patients, double unilimb Z-plasty in 7 patients, and triple unilimb Z-plasty in 5 patients. In all cases, the notch or elevated cupid's bow was corrected, the surgical scar was minimal, and philtrum reconstruction was satisfactory. Minor scar revision was performed in 4 patients. Cleft lip nasal deformity was corrected in fifteen patients.

Conclusions:

The technique adopted here causes minimal scarring, facilitates the formation of an anatomical philtrum, preserves the continuity and function of the muscle, and presents sufficient elevation of the philtral column.
Mapping the evolutionary landscape of Zika virus infection in immunocompromised mice
Authors: Noval Maria G. , Rangel Margarita V. , Johnson Katherine E. , Jesus Elfie De , Gerber Adam , Schuster Samantha , Cadwell Ken , Ghedin Elodie , Stapleford Kenneth A.
Published: November 2019

The fundamental basis of how arboviruses evolve in nature and what regulates the adaptive process remain unclear. To address this problem, we established a Zika virus (ZIKV) vector-borne transmission system in immunocompromised mice that mimics evolutionary characteristics of ZIKV infection in humans. Using this system, we defined factors that influence the evolutionary landscape of ZIKV infection and show that transmission route and specific organ microenvironments impact viral diversity and defective viral genome (DVG) production. In addition, we identified in mice the emergence of ZIKV mutants previously seen in natural infections, including variants present in currently circulating strains, as well as mutations unique to the mouse infections. With these studies, we have established an insect-to-mouse transmission model to study ZIKV evolution. We also defined how organ microenvironments and infection route impact the ZIKV evolutionary landscape, providing a deeper understanding of the factors that regulate arbovirus evolution and emergence.
Quantitative analysis of the physiological contributions of glucose to the TCA cycle
Authors: Liu Shiyu , Dai Ziwei , Cooper Daniel E. , Kirsch David G. , Locasale Jason W.
Published: November 2019

The carbon source for catabolism in vivo is a fundamental question in metabolic physiology. Limited by data and rigorous mathematical analysis, controversy exists over the nutritional sources for carbon in the tricarboxylic acid (TCA) cycle under physiological settings. Using isotope-labeling data in vivo across several experimental conditions, we construct multiple models of central carbon metabolism and develop methods based on metabolic flux analysis (MFA) to solve for the preferences of glucose, lactate, and other nutrients used in the TCA cycle across many tissues. We show that in nearly all circumstances, glucose contributes more than lactate as a nutrient source for the TCA cycle. This conclusion is verified in different animal strains from different studies, different administrations of 13C glucose, and is extended to multiple tissue types. Thus, this quantitative analysis of organismal metabolism defines the relative contributions of nutrient fluxes in physiology, provides a resource for analysis of in vivo isotope tracing data, and concludes that glucose is the major nutrient used for catabolism in mammals.
Trophoblast paracrine signaling regulates placental hematoendothelial niche
Authors: Home Pratik , Ghosh Ananya , Kumar Ram Parikshan , Ganguly Avishek , Bhattacharya Bhaswati , Islam Md. Rashedul , Ray Soma , Gunewardena Sumedha , Paul Soumen
Published: November 2019

The placenta acts as a major organ for hematopoiesis. It is believed that placental hematopoietic stem and progenitor cells (HSPCs) migrate to the fetal liver to ensure optimum hematopoiesis in the developing embryo. The labyrinth vasculature in a mid-gestation mouse placenta provides a niche for the definitive hematopoietic stem cell (HSC) generation and expansion. It has been proposed that these processes are regulated by a host of paracrine factors secreted by trophoblast giant cells (TGCs) at the maternal-fetal interface. However, the molecular mechanism by which the TGCs regulate the hematoendothelial niche in a developing placenta is yet to be defined. Using a TGC-specificGata2andGata3double knockout mouse model, we show that the loss of GATA2 and GATA3 at the TGC layer leads to fetal growth retardation and embryonic death due to disruptions in the delicate hematopoietic-angiogenic balance in the developing placenta. Using single-cell RNA-Seq analyses, we also show that the loss of GATA factors in the TGCs results in the loss of HSC population within the placental labyrinth and is associated with defective placental angiogenesis. Interestingly, we also found that this TGC-specific GATA factor-loss leads to impaired differentiation and distribution of trophoblast progenitor cells. Our study helps to define the GATA-dependent non-autonomous signaling mechanisms of the primary parietal trophoblast giant cells by which it regulates the delicate hematopoietic-angiogenic balance in the developing placenta.
Chemical genetics strategy to profile kinase target engagement reveals role of FES in neutrophil phagocytosis via SYK activation
Authors: van der Wel Tom , Hilhorst Riet , den Dulk Hans , van den Hooven Tim , Prins Nienke M. , Wijnakker Joost A.P.M. , Florea Bogdan I. , Lenselink Eelke B. , van Westen Gerard J.P. , Ruijtenbeek Rob , Overkleeft Herman S. , Kaptein Allard , Barf Tjeerd , van der Stelt Mario
Published: November 2019

Chemical tools and methods that report on target engagement of endogenously expressed protein kinases by small molecules in human cells are highly desirable. Here, we describe a chemical genetics strategy that allows the study of non-receptor tyrosine kinase FES, a promising therapeutic target for cancer and immune disorders. Precise gene editing was used in combination with a rationally designed, complementary fluorescent probe to visualize endogenous FES kinase in HL-60 cells. We replaced a single oxygen atom by a sulphur in a serine residue at the DFG-1 position of the ATP-binding pocket in an endogenously expressed kinase, thereby sensitizing the engineered protein towards covalent labeling and inactivation by a fluorescent probe. The temporal control offered by this strategy allows acute inactivation of FES activity both during myeloid differentiation and in terminally differentiated neutrophils. Our results show that FES activity is dispensable for differentiation of HL-60 cells towards macrophages. Instead, FES plays a key role in neutrophil phagocytosis by activation of SYK kinase, a central regulator of immune function in neutrophils. This strategy holds promise as a target validation method for kinases.
CRISPR-based modular assembly of a UAS-cDNA/ORF plasmid library for more than 5500 Drosophila genes conserved in humans
Authors: Wei Ping , Xue Wen , Zhao Yun , Ning Guang , Wang Jiwu
Published: November 2019

Construction of a genome-wide transgenic UAS-cDNA/ORF library in Drosophila based on the binary GAL4/UAS system has been severely hampered by technical difficulties, although genome-wide cDNA or ORF resources of Drosophila, human, and mouse have been publicly available for more than a decade. Here, we developed a new method named CRISPR-based modular assembly (CRISPRmass) for the high-throughput construction of a genome-wide UAS-cDNA/ORF library from publicly available cDNA/ORF resources. Through cleavage of shared vector sequences of cDNA/ORF plasmids by CRISPR/Cas9 and subsequent insertion of UAS modules by Gibson assembly, the procedure of construction of such a library by CRISPRmass is standardized as massively parallel two-step test tube reactions before bacterial transformation. Using CRISPRmass, we generated 5551 UAS-cDNA/ORF constructs covering 83% of the Drosophila genes conserved in humans in the Drosophila Genomics Resource Center (DGRC) Gold Collection, and among them, 5518 were generated within 3 mo by three people. Our results show that CRISPRmass allows modulization, simplicity, efficiency, and adaptability in the generation of a genome-wide UAS-cDNA/ORF plasmid library by using publicly available cDNA/ORF resources. CRISPRmass can be applied to editing various genome-wide libraries in general and is an alternative to Gateway technology in high-throughput plasmid library editing. Furthermore, the more than 5500 UAS-cDNA/ORF plasmids of Drosophila genes serve as a powerful resource for gain-of-function (GOF) screening in cultured cells and for generation of a transgenic UAS-cDNA/ORF library in Drosophila.
Multireflection grazing-incidence X-ray diffraction: a new approach to experimental data analysis
Authors: Marciszko-Wiąckowska Marianna , Oponowicz Adrian , Baczmański Andrzej , Wróbel Miroslaw , Braham Ch. , Wawszczak R.
Published: November 2019

The multireflection grazing-incidence X-ray diffraction method is used to test surface stresses at depths of several micrometres in the case of metal samples. This work presents new ways of analysing experimental data obtained by this method for Ni samples exhibiting significant elastic anisotropy of crystals. Three different methods of determining biaxial stresses and lattice parameter were compared. In the first approach, the calculations were performed using the linear least-squares method, and then two simplified procedures based on simple linear regression (weighted and non-weighted) were applied. It was found that all the tested methods give similar results, i.e. almost equal values of the determined stresses and lattice parameters and the uncertainties of their determination. The advantage of analyses based on simple linear regression is their simplicity and straightforward interpretation, enabling easy verification of the influence of the crystallographic texture and the presence of shear stresses, as well as graphical determination of the stress-free lattice parameter.
Examining a synchrotron-based approach forin situanalyses of Al speciation in plant roots
Authors: Li Zhigen , Wang Peng , Menzies Neal W. , McKenna Brigid A. , Karunakaran Chithra , Dynes James J. , Arthur Zachary , Liu Na , Zuin Lucia , Wang Dongniu , Kopittke Peter M.
Published: November 2019

Aluminium (Al)K- andL-edge X-ray absorption near-edge structure (XANES) has been used to examine Al speciation in minerals but it remains unclear whether it is suitable forin situanalyses of Al speciation within plants. The XANES analyses for nine standard compounds and root tissues from soybean (Glycine max), buckwheat (Fagopyrum tataricum), and Arabidopsis (Arabidopsis thaliana) were conductedin situ. It was found thatK-edge XANES is suitable for differentiating between tetrahedral coordination (peak of 1566 eV) and octahedral coordination (peak of 1568 to 1571 eV) Al, but not suitable for separating Al binding to some of the common physiologically relevant compounds in plant tissues. The AlL-edge XANES, which is more sensitive to changes in the chemical environment, was then examined. However, the poorer detection limit for analyses prevented differentiation of the Al forms in the plant tissues because of their comparatively low Al concentration. Where forms of Al differ markedly,K-edge analyses are likely to be of value for the examination of Al speciation in plant tissues. However, the apparent inability of AlK-edge XANES to differentiate between some of the physiologically relevant forms of Al may potentially limit its application within plant tissues, as does the poorer sensitivity at theL-edge.