bluuebunny/crossref_metadata_2025 huggingface dataset:
GPU-accelerated periodic source identification in large-scale surveys: measuring P and P
Authors: Katz Michael L , Cooper Olivia R , Coughlin Michael W , Burdge Kevin B , Breivik Katelyn , Larson Shane L
Published: February 2021

Many inspiraling and merging stellar remnants emit both gravitational and electromagnetic radiation as they orbit or collide. These gravitational wave events together with their associated electromagnetic counterparts provide insight about the nature of the merger, allowing us to further constrain properties of the binary. With the future launch of the Laser Interferometer Space Antenna (LISA), follow-up observations and models are needed of ultracompact binary (UCB) systems. Current and upcoming long baseline time domain surveys will observe many of these UCBs. We present a new fast periodic object search tool capable of searching for generic periodic signals based on the conditional entropy algorithm. This new implementation allows for a grid search over both the period (P) and the time derivative of the period ($\dot{P}$). To demonstrate the usage of this tool, we use a small, hand-picked subset of a UCB population generated from the population synthesis code cosmic , as well as a custom catalogue for varying periods at fixed intrinsic parameters. We simulate light curves as likely to be observed by future time domain surveys by using an existing eclipsing binary light-curve model accounting for the change in orbital period due to gravitational radiation. We find that a search with $\dot{P}$ values is necessary for detecting binaries at orbital periods less than ∼10 min. We also show it is useful in finding and characterizing binaries with longer periods, but at a higher computational cost. Our code is called gce (GPU-accelerated Conditional Entropy). It is available on Github (https://github.com/mikekatz04/gce).
Exotic image formation in strong gravitational lensing by clusters of galaxies – I. Cross-section
Authors: Meena Ashish Kumar , Bagla Jasjeet Singh
Published: February 2021

In a recent paper, we have discussed the higher order singularities in gravitational lensing. We have shown that a singularity map, comprising A3- lines and unstable (point) singularities (A4 and D4), is a compact representation of high magnification regions corresponding to a given lens model for all possible source redshifts. It marks all the optimal locations for deep surveys in the lens plane. Here, we present singularity maps for 10 different clusters lenses selected from the Hubble Frontier fields (HFF) and the Reionization Lensing Cluster Survey (RELICS) surveys. We have identified regions in the lens plane with a high magnification for sources up to redshift 10. To determine the dependence of unstable (point) singularities on lens mass model reconstruction techniques, we compared singularity maps corresponding to the different mass models (provided by various groups in the HFF survey) for each cluster lens. We find that the non-parametric (free-form) method of lens mass reconstruction yields the least number of point singularities. In contrast, mass models reconstructed by various groups using a parametric approach have a significantly larger number of point singularities. We also estimate the number of galaxies lying near these unstable (point) singularities, which can be observed with the James Webb Space Telescope (JWST). We find that we expect to get at least one hyperbolic umbilic and one swallowtail image formation for a source at z > 1 for every five clusters with JWST. These numbers are much higher than earlier estimates.
Nested sampling with plateaus
Authors: Fowlie Andrew , Handley Will , Su Liangliang
Published: February 2021

It was recently emphasized that in the presence of plateaus in the likelihood function nested sampling (NS) produces faulty estimates of the evidence and posterior densities. After informally explaining the cause of the problem, we present a modified version of NS that handles plateaus and can be applied retrospectively to NS runs from popular NS software using anesthetic. In the modified NS, live points in a plateau are evicted one by one without replacement, with ordinary NS compression of the prior volume after each eviction but taking into account the dynamic number of live points. The live points are replenished once all points in the plateau are removed. We demonstrate it on a number of examples. Since the modification is simple, we propose that it becomes the canonical version of Skilling’s NS algorithm.
Synbiotics improve clinical indicators of ulcerative colitis: systematic review with meta-analysis
Authors: Rufino Marcos Natal , da Costa Airan Lobo , Jorge Eloisa Nascimento , Paiano Viviane Ferreira , Camparoto Marjori Leiva , Keller Rogéria , Bremer-Neto Hermann
Published: February 2021

Context

Inflammatory bowel diseases are chronic, relapsing diseases that compromise life quality and expectancy. The increased incidence and prevalence of these diseases reinforce the need for research on prevention, therapy, and management innovations. Synbiotics (ie, probiotic plus prebiotic combinations) are suggested as an alternative or complementary therapy to conventional treatments for inflammatory bowel disease.

Objective

The aim for this systematic review was to gather and analyze data from randomized controlled trials to provide more information to increase the current evidence level about the safety and efficacy of synbiotic use as a supplemental treatment for ulcerative colitis.

Data Sources

Searches were performed in the Medline, Science Direct, Scielo, Scopus, and Embase databases between January 2017 and March 2019, using the keywords “colitis” and ”synbiotics”.

Data Extraction

The data extraction method performed for each trial was based on the recommendations of the Consolidated Standards of Reporting Trials for randomized clinical trials. The trials included in this meta-analysis presented low risk of bias, based on the Cochrane Handbook for Systematic Reviews of Interventions guidelines.

Data Analysis

The results demonstrated that synbiotics significantly improved colonic endoscopic and histologic scores, the Clinical Activity Index, serum C-reactive protein levels, intestinal microbiota, Bowel Habits Index, and levels of messenger RNAs, tumor necrosis factor-α, interleukin-1α, interleukin-10, and myeloperoxidase in the patients. In addition, the use of synbiotics increased probiotic microorganisms, reduced proinflammatory colonic cytokines, and elevated anti-inflammatory cytokines.

Conclusions

Therefore, the results of this meta-analysis reinforce the evidence that synbiotics provide benefits to patients when used as an alternative or complementary therapy for those with ulcerative colitis.
Ectopic maltase alleviates dwarf phenotype and improves plant frost tolerance of maltose transporter mutants
Authors: Cvetkovic Jelena , Haferkamp Ilka , Rode Regina , Keller Isabel , Pommerrenig Benjamin , Trentmann Oliver , Altensell Jacqueline , Fischer-Stettler Michaela , Eicke Simona , Zeeman Samuel C , Neuhaus H Ekkehard
Published: February 2021

Maltose, the major product of starch breakdown in Arabidopsis (Arabidopsis thaliana) leaves, exits the chloroplast via the maltose exporter1 MEX1. Consequently, mex1 loss-of-function plants exhibit substantial maltose accumulation, a starch-excess phenotype and a specific chlorotic phenotype during leaf development. Here, we investigated whether the introduction of an alternative metabolic route could suppress the marked developmental defects typical for mex1 loss-of-function mutants. To this end, we ectopically expressed in mex1  chloroplasts a functional maltase (MAL) from baker’s yeast (Saccharomyces cerevisiae, chloroplastidial MAL [cpMAL] mutants). Remarkably, the stromal MAL activity substantially alleviates most phenotypic peculiarities typical for mex1 plants. However, the cpMAL lines contained only slightly less maltose than parental mex1 plants and their starch levels were, surprisingly, even higher. These findings point to a threshold level of maltose responsible for the marked developmental defects in mex1. While growth and flowering time were only slightly retarded, cpMAL lines exhibited a substantially improved frost tolerance, when compared to wild-types. In summary, these results demonstrate the possibility to bypass the MEX1 transporter, allow us to differentiate between possible starch-excess and maltose-excess responses, and demonstrate that stromal maltose accumulation prevents frost defects. The latter insight may be instrumental for the development of crop plants with improved frost tolerance.
MONTE CARLO DOSE ASSESSMENT IN DENTAL CONE-BEAM COMPUTED TOMOGRAPHY
Authors: Kim Jinwoo , Jeon Hosang , Kyung Kim Ho
Published: February 2021

Most dental cone-beam computed tomography (CBCT) uses an x-ray beam field covering the maxillomandibular region and the width-truncated detector geometry. The spatial dose distribution in dental CBCT is analyzed in terms of local primary and remote secondary doses by using a list-mode analysis of x-ray interactions obtained from the Monte Carlo simulations. The patient-dose benefit due to the width-truncated detector geometry is also investigated for a wide range of detector offsets. The developed dose estimation agrees with the measurement in a relative error of 7.7%. The secondary dose outside of the irradiation field becomes larger with increasing tube voltage. The dose benefit with the width-truncated geometry linearly increases as the detector-offset width is decreased. Leaving the CT image quality out of the account, the MC results reveal that the operation of dental CBCT with a lower tube voltage and a smaller detector-offset width is beneficial to the patient dose.
A Lower Tidal Volume Regimen during One-lung Ventilation for Lung Resection Surgery Is Not Associated with Reduced Postoperative Pulmonary Complications
Authors: Colquhoun Douglas A. , Leis Aleda M. , Shanks Amy M. , Mathis Michael R. , Naik Bhiken I. , Durieux Marcel E. , Kheterpal Sachin , Pace Nathan L. , Popescu Wanda M. , Schonberger Robert B. , Kozower Benjamin D. , Walters Dustin M. , Blasberg Justin D. , Chang Andrew C. , Aziz Michael F. , Harukuni Izumi , Tieu Brandon H. , Blank Randal S.
Published: February 2021

Background

Protective ventilation may improve outcomes after major surgery. However, in the context of one-lung ventilation, such a strategy is incompletely defined. The authors hypothesized that a putative one-lung protective ventilation regimen would be independently associated with decreased odds of pulmonary complications after thoracic surgery.

Methods

The authors merged Society of Thoracic Surgeons Database and Multicenter Perioperative Outcomes Group intraoperative data for lung resection procedures using one-lung ventilation across five institutions from 2012 to 2016. They defined one-lung protective ventilation as the combination of both median tidal volume 5 ml/kg or lower predicted body weight and positive end-expiratory pressure 5 cm H2O or greater. The primary outcome was a composite of 30-day major postoperative pulmonary complications.

Results

A total of 3,232 cases were available for analysis. Tidal volumes decreased modestly during the study period (6.7 to 6.0 ml/kg; P < 0.001), and positive end-expiratory pressure increased from 4 to 5 cm H2O (P < 0.001). Despite increasing adoption of a “protective ventilation” strategy (5.7% in 2012 vs. 17.9% in 2016), the prevalence of pulmonary complications did not change significantly (11.4 to 15.7%; P = 0.147). In a propensity score matched cohort (381 matched pairs), protective ventilation (mean tidal volume 6.4 vs. 4.4 ml/kg) was not associated with a reduction in pulmonary complications (adjusted odds ratio, 0.86; 95% CI, 0.56 to 1.32). In an unmatched cohort, the authors were unable to define a specific alternative combination of positive end-expiratory pressure and tidal volume that was associated with decreased risk of pulmonary complications.

Conclusions

In this multicenter retrospective observational analysis of patients undergoing one-lung ventilation during thoracic surgery, the authors did not detect an independent association between a low tidal volume lung-protective ventilation regimen and a composite of postoperative pulmonary complications.

Editor’s Perspective

What We Already Know about This Topic

What This Article Tells Us That Is New
Incidence of and Risk Factors for Failed Induction of Labor Using a Contemporary Definition
Authors: Freret Taylor S. , Woods Gregory T. , James Kaitlyn E. , Kaimal Anjali J. , Clapp Mark A.
Published: February 2021

OBJECTIVE:

To estimate the incidence of failed induction of labor and the associated patient risk factors.

METHODS:

We performed a case–control study from a cohort of nulliparous women who delivered between 39 and 41 weeks of gestation after an induction of labor in one of seven hospitals. Cases of failed induction were defined using the Obstetric Care Consensus criteria (ie, cesarean delivery performed in early labor [less than 6 cm dilatation] after at least 12 hours of oxytocin administration from membrane rupture). For each case of failed induction, the next four women who did not meet the criteria for failed induction of labor were selected for the control group, matched by hospital. We identified characteristics associated with failed induction of labor using a multivariable conditional logistic regression that was constructed with backward stepwise method for variable selection.

RESULTS:

Across the hospitals, 4,123 of 10,175 nulliparous women were induced (40.5%), of whom 82 had a failed induction of labor (2.0%). A total of 328 women were selected for the matched control group. Baseline characteristics were similar between the groups. Compared with women in the control group, women with a failed induction were more likely to have a delivery body mass index (BMI) of 40 or higher (28.0 vs 8.2%, P<.001), shorter height (mean 63.9 vs 64.8 inches, P=.01), and closed cervix on admission (41.5 vs 24.1%, P=.002). Factors significantly associated with induction failure in the multivariable model included: 1) delivery BMI (adjusted odds ratio [aOR] 7.93, 95% CI 3.48–18.09, for BMI 40 or higher relative to BMI lower than 30, 2) height in inches (aOR 0.89, 95% CI 0.80–0.98), and 3) number of centimeters dilated on admission 2 or more (aOR 0.30, 95% CI 0.14–0.65).

CONCLUSION:

Failed induction of labor occurs infrequently. Risk factors include shorter height, BMI 40 or higher, and cervical dilatation of less than 2 cm on admission. Even so, most women with these risk factors will not experience failed labor induction.
Comparison of Surgical Outcomes After Total Laparoscopic Hysterectomy or Total Vaginal Hysterectomy for Large Uteri
Authors: Sailofsky Sybil , Darin Christina , Alfahmy Anood , Sheyn David
Published: February 2021

OBJECTIVE:

To compare surgical outcomes between total laparoscopic hysterectomy and total vaginal hysterectomy with uterine weight greater than 250 g.

METHODS:

We conducted a retrospective cohort study using data from American College of Surgeons’ National Quality Improvement Project Hysterectomy Specific Database. Women with uterine weight greater than 250 g undergoing hysterectomy for benign indications by total laparoscopic hysterectomy or total vaginal hysterectomy were matched by propensity scores, which were calculated using preoperative characteristics and uterine weight. Total vaginal hysterectomy was matched to total laparoscopic hysterectomy at a ratio of 1:2. Pairwise analysis was performed using Wilcoxon rank-sum and Fisher exact tests as appropriate. Multivariable logistic regression was performed to identify the independent effect of total vaginal hysterectomy on surgical outcomes.

RESULTS:

There were 1,870 total vaginal hysterectomies that were matched to 3,740 total laparoscopic hysterectomies. No differences in preoperative demographics and comorbidities were seen for the patients. Uterine weight was similar for both groups: 376 g (interquartile range 293–501) for total vaginal hysterectomy and 384 g (interquartile range 302–515) for total laparoscopic hysterectomy (odds ratio [OR] 0.98, 95% CI 0.92–1.09). The rate of composite major complications was similar between total vaginal hysterectomy and total laparoscopic hysterectomy (4.3% vs 5.3%, OR 0.80, 95% CI 0.61–1.05). Intraoperative cystotomies were higher with total vaginal hysterectomy (0.8% vs 0.3%, OR 2.74, 95% CI 1.17–6.61), and ureteral injuries were more common with total laparoscopic hysterectomy (1.2% vs 0.2%, OR 0.12, 95% CI 0.02–0.38). Total vaginal hysterectomy operating time was significantly shorter compared with total laparoscopic hysterectomy (77 minutes, interquartile range 56–111 vs 122 minutes, interquartile range 91–164; OR 0.69, 95% CI 0.42–0.89). After adjusting for confounders, total vaginal hysterectomy was not found to be independently associated with major morbidity (adjusted odds ratio [aOR] 0.95, 95% CI 0.18–5.11) and was associated with a lower probability of operating times exceeding 2.5 hours (aOR 0.31, 95% CI 0.27–0.43).

CONCLUSION:

In patients matched by uterine size and preoperative characteristics, total vaginal hysterectomy is not associated with an increased composite risk of major surgical morbidity or other adverse surgical outcomes.
Sex, Hormones, Immune Functions, and Susceptibility to Coronavirus Disease 2019 (COVID-19)–Related Morbidity
Authors: Gotluru Chitra , Roach Allison , Cherry Sheldon H. , Runowicz Carolyn D.
Published: February 2021

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes coronavirus disease 2019 (COVID-19), uses two primary receptors, type II transmembrane serine protease and angiotensin-converting enzyme-2, for priming and cellular invasion, respectively. Both proteins have been demonstrated to be present in different concentrations in females and males, which may explain a mechanism for the reported higher case-fatality rate in males. Despite the known sex difference in COVID-19 disease mortality, preliminary data suggest there are certain female populations, including pregnant and menopausal women and possibly polycystic ovarian syndrome patients who are more susceptible to COVID-19–related morbidity. This commentary analyzes the interplay between sex differences, hormones, and the immune function in each of these populations with respect to the risk and severity of COVID-19 and proposes biological rationales to explain these differences.
Ensuring Equitable Implementation of Telemedicine in Perinatal Care
Authors: Ukoha Erinma P. , Davis Kelly , Yinger Meredith , Butler Blythe , Ross Tamia , Crear-Perry Joia , Perron-Burdick Misa , Nijagal Malini A.
Published: February 2021

The use of telemedicine in U.S. perinatal care has drastically increased during the coronavirus disease 2019 (COVID-19) pandemic, and will likely continue given the national focus on high-value, patient-centered care. If implemented in an equitable manner, telemedicine has the potential to reduce disparities in care access and related outcomes that stem from systemic racism, implicit biases and other forms of discrimination within our health care system. In this commentary, we address implementation factors that should be considered to ensure that disparities are not widened as telemedicine becomes more integrated into care delivery.
Measuring Female Veterans' Prepregnancy Wellness Using Department of Veterans Affairs' Health Record Data
Authors: Quinn Deirdre A. , Mor Maria K. , Sileanu Florentina E. , Zhao Xinhua , Callegari Lisa S. , Zephyrin Laurie C. , Frayne Daniel J. , Borrero Sonya
Published: February 2021

OBJECTIVE:

To estimate the feasibility of using measures developed by the Clinical Workgroup of the National Preconception Health and Health Care Initiative to assess women's prepregnancy wellness in a large health care system.

METHODS:

We examined Department of Veterans Affairs' (VA) national administrative data, including inpatient, outpatient, fee-basis, laboratory, pharmacy, and screening data for female veterans aged 18–45 who had at least one pregnancy outcome (ectopic pregnancy, spontaneous abortion, stillbirth, and live birth) during fiscal years 2010–2015 and a VA primary care visit within 1 year before last menstrual period (LMP). LMP was estimated from gestational age at the time of pregnancy outcome, then used as a reference point to assess eight prepregnancy indicators from the Workgroup consensus measures (eg, 3 or 12 months before LMP).

RESULTS:

We identified 19,839 pregnancy outcomes from 16,034 female veterans. Most (74.9%) pregnancies ended in live birth; 22.6% resulted in spontaneous abortion or ectopic pregnancy, and 0.5% in stillbirth. More than one third (39.2%) of pregnancies had no documentation of prenatal care within 14 weeks of LMP. Nearly one third (31.2%) of pregnancies occurred in women with obesity. Among pregnancies with a recent relevant screening, 29.2% were positive for smoking and 28.4% for depression. More than half (57.4%) of pregnancies in women with preexisting diabetes did not have documentation of optimal glycemic control. Absence of sexually transmitted infection screening in the year before or within 3 months of LMP was high. Documentation of prenatal folic acid use was also high. Exposure in the same timeframe to six classes of teratogenic medications was low.

CONCLUSION:

Despite limitations of administrative data, monitoring measures of prepregnancy wellness can provide benchmarks for improving women's health across health care systems and communities. Areas for intervention to improve female veterans' prepregnancy wellness include healthy weight, optimizing control of diabetes before pregnancy, and improved use and documentation of key prepregnancy health screenings.
Obesity as a Predictor of Outcomes in Type III and Type IV Supracondylar Humerus Fractures
Authors: Nazareth Alexander , Schur Mathew , Schroeder Amanda J. , Whitlock Patrick W. , Skaggs David L. , Goldstein Rachel Y.
Published: February 2021

Objectives:

To investigate the association of obesity with fracture characteristics and outcomes of operatively treated pediatric supracondylar humerus fractures.

Design:

Retrospective multicenter.

Setting:

Two Level I pediatric hospitals.

Patients:

Patients (age <18 years) with operatively treated Gartland type III and type IV fractures 2010–2014.

Intervention:

Closed or open reduction and percutaneous pinning of supracondylar humerus fractures.

Main Outcome Measure:

Incidence of Gartland IV fracture, preoperative nerve palsy, open reduction and complication rates.

Results:

Patients in the obese group had a significantly higher likelihood of having a Gartland IV fracture (not obese: 17%; obese: 35%; P = 0.007). There was a significantly higher incidence of nerve palsy on presentation in the obese group (not obese: 20%; obese: 33%; P = 0.03). No significant differences were found between groups regarding incidence of open reduction, compartment syndrome, and rates of reoperation.

Conclusions:

The present study demonstrates that obese children with a completely displaced supracondylar humerus fractures have an increased risk of Gartland type IV and preoperative nerve palsy compared with normal weight children.

Level of Evidence:

Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.
Preoperative PROMIS Scores Predict Postoperative Outcomes in Lumbar Spine Surgery Patients
Authors: Snavely Joseph E. , Weiner Joseph A. , Johnson Daniel J. , Hsu Wellington K. , Patel Alpesh A.
Published: February 2021

Study Design.

Retrospective case series.

Objective.

Our objective was to examine the ability of preoperative Patient-reported Outcomes Measurement Information System (PROMIS) scores to predict postoperative achievement of a minimum clinically important difference (MCID) in outcome scores following lumbar spine surgery.

Summary of Background Data.

PROMIS is a computer adaptive testing system that has been validated in spine surgery patients. PROMIS allows for more efficient and personalized data collection compared to legacy assessment tools.

Methods.

A total of 138 patients who underwent lumbar spine surgery at a single institution completed PROMIS Physical Function (PF) and Pain Interference (PI) scores preoperatively and at 3, 12, and 24 months postoperatively. Univariate and multivariate analyses of PROMIS scores and clinical factors were performed. Receiver-operating characteristic curves were calculated to determine the ability of preoperative scores to predict postoperative achievement of an MCID of 8. PF and PI t score MCID achievement threshold values with 90% specificity were calculated.

Results.

Preoperative PROMIS PF and PI scores were significantly correlated to achievement of postoperative MCID after multivariate analysis. Patients with worse preoperative scores were more likely to achieve MCID. Preoperative PF and PI scores showed strong predictive value in determining ability to achieve postoperative MCID with respective area under the curve of 0.85 and 0.82. A preoperative PF threshold T-score of 31.6 had a 64% chance of achieving postoperative MCID, while a preoperative PI threshold t score of 67.8 had an 86% chance of achieving postoperative MCID.

Conclusion.

Preoperative PROMIS PF and PI scores predicted improvement in postoperative PROMIS scores in lumbar spine surgery patients as worse preoperative scores correlated to improved PROMIS scores postoperatively. The calculated threshold t scores showed the ability to predict improvement in postoperative PROMIS scores. Preoperative PROMIS data may be useful in surgical decision-making and improved patient education regarding postoperative outcomes.

Level of Evidence: 4
Prediction of Recurrence in Pyogenic Vertebral Osteomyelitis by Artificial Neural Network Using Time-series Data of C-Reactive Protein
Authors: Kim Jihye , Ryu Hwan , Kim Seok Woo , Oh Jae-Keun , Kim Tae-Hwan
Published: February 2021

Study Design.

A retrospective cohort study.

Objective.

The aim of this study was to develop recurrence-prediction models of pyogenic vertebral osteomyelitis (PVO).

Summary of Background Data.

Prediction of recurrence in PVO is crucial to avoid additional prolonged antibiotic therapy and aggressive spinal surgery and to reduce mortality. However, prediction of PVO recurrence by previously identified, initial risk factors is limited in PVO patients who exceptionally require prolonged antibiotic therapy and experience various clinical events during the treatment. We hypothesized that time-series analysis of sequential C-reactive protein (CRP) routinely measured to estimate the response to the antibiotics in PVO patients could reflect such long treatment process and increase the power of the recurrence-prediction model.

Methods.

A retrospective study was performed to develop a PVO recurrence-prediction model, including initial risk factors and time-series data of CRP. Of 704 PVO patients, 493 and 211 were divided into training and test cohorts, respectively. Conventional stepwise logistic regression and artificial neural network (ANN) models were created from the training cohort, and the predictions of recurrence in the test cohort were compared.

Results.

Prediction models using initial risk factors showed poor sensitivity (4.7%) in both conventional logistic model and ANN models. However, baseline ANN models using time-series CRP data showed remarkably increased sensitivity (55.8%–60.5%). Ensemble ANN model using both initial risk factors and time-series CRP data showed additional benefit in prediction power.

Conclusion.

The recurrence-prediction models for PVO created only using the initial risk factors showed low sensitivity, regardless of statistical method. However, ANN models using time-series data of CRP values and their ensemble model showed considerably increased prediction power. Therefore, clinicians treating PVO patients should pay attention to the treatment response including changes of CRP levels to identify high-risk patients for recurrence, and further studies to develop recurrence-prediction model for PVO should focus on the treatment response rather than initial risk factors.

Level of Evidence: 4
Keratin Biomaterials Improve Functional Recovery in a Rat Spinal Cord Injury Model
Authors: Zabarsky Zachary K. , Dean Gabriella M. , Luo Tianyi David , Marquez-Lara Alejandro , Jinnah Alexander H. , Van Dyke Mark , Smith Thomas L.
Published: February 2021

Study Design.

Laboratory study using a rat T9 contusion model of spinal cord injury (SCI).

Objective.

The purpose of this study was to evaluate which method of delivery of soluble keratin biomaterials would best support functional restoration through the macrophage polarization paradigm.

Summary of Background Data.

SCI is a devastating neurologic event with complex pathophysiological mechanisms that currently has no cure. After injury, macrophages and resident microglia are key regulators of inflammation and tissue repair exhibiting phenotypic and functional plasticity. Keratin biomaterials have been demonstrated to influence macrophage polarization and promote the M2 anti-inflammatory phenotype that attenuates inflammatory responses.

Methods.

Anesthetized female Lewis rats were subjected to moderate T9 contusion SCI and randomly divided into: no therapy (control group), an intrathecally injected keratin group, and a keratin-soaked sponge group (n = 11 in all groups). Functional recovery assessments were obtained at 3- and 6-weeks post-injury (WPI) using gait analysis performed with the DigiGait Imaging System treadmill and at 1, 3, 7, 14, 21, 28, 35, and 42 days post-injury by the Basso, Beattie, Bresnahan (BBB) locomotor rating scale. Histology and immunohistochemistry of serial spinal cord sections were performed to assess injury severity and treatment efficacy.

Results.

Compared to control rats, applying keratin materials after injury improved functional recovery in certain gait parameters and overall trended toward significance in BBB scores; however, no significant differences were observed with tissue analysis between groups at 6 WPI.

Conclusion.

Results suggest that keratin biomaterials support some locomotor functional recovery and may alter the acute inflammatory response by inducing macrophage polarization following SCI. This therapy warrants further investigation into treatment of SCI.

Level of Evidence: N/A
Infra-adjacent Segment Disease After Lumbar Fusion
Authors: Nessim Adam , Cho Woojin , Yang Xiuyi Alexander , Applebaum Ariella , Sekerak Richard , Brill Sam , Kim Soo Yeon
Published: February 2021

Study Design.

Cross-sectional observational cohort study.

Objective.

The aim of this study was to determine the incidence and risk factors associated with the development of sacroiliac joint (SIJ) dysfunction following lumbosacral fusion.

Summary of Background Data.

Adjacent segment degeneration to both proximal and distal areas of spinal fusion is a postoperative complication of lumbar fusion. Various studies examined supra-adjacent degeneration following lumbar fusion, but few focused on infra-adjacent degeneration. In lumbosacral fusion, fusion extends to the sacrum, placing increased stress on the SIJ.

Methods.

A total of 2069 sequential patients who underwent lumbosacral fusion surgery from 2008 to 2018 at a single academic medical center were retrospectively reviewed. Patients who subsequently developed SIJ dysfunction were identified. SIJ dysfunction was defined as patients who met the diagnostic criteria with physical examination and received an SIJ injection with clinical evidence of improvement. Controls, without subsequent SIJ dysfunction, were matched with cases based on levels of fusion, age, sex, and body mass index. Pre-and postoperative pelvic parameters were measured, including pelvic incidence, pelvic tilt (PT), sacral slope, lumbar lordosis, lumbosacral angle, L4 incidence and L5 incidence

Results.

Of 2069 patients who underwent lumbosacral fusion, 81 patients (3.9%) met criteria for SIJ dysfunction. Measurements were made for 47 of 81 patients who had SIJ dysfunction, that had both pre- and post-operative imaging. Measurements for 44 matched controls were taken. Postoperative PT was significantly lower in SIJ dysfunction patients compared to controls (20.82° ± 2.19° vs. 27.28° ± 2.30°; P < 0.05), as was L5 incidence (28.64° ± 3.38° vs. 37.11° ± 3.50°; P < 0.05).

Conclusion.

Incidence of the SIJ dysfunction after lumbosacral fusion surgery was 3.9% and these patients had a significantly lower PT and L5 incidence compared to the control group. Significantly low PT may be derived from weak hamstring muscles, predisposing a patient to SIJ dysfunction. Therefore, hamstring muscle strengthening exercise for patients with decreased PT after lumbosacral fusion may decrease the incidence of SIJ dysfunction.

Level of Evidence: 3
Sepsis Subclasses: A Framework for Development and Interpretation*
Authors: DeMerle Kimberley M. , Angus Derek C. , Baillie J. Kenneth , Brant Emily , Calfee Carolyn S. , Carcillo Joseph , Chang Chung-Chou H. , Dickson Robert , Evans Idris , Gordon Anthony C. , Kennedy Jason , Knight Julian C. , Lindsell Christopher J. , Liu Vincent , Marshall John C. , Randolph Adrienne G. , Scicluna Brendon P. , Shankar-Hari Manu , Shapiro Nathan I. , Sweeney Timothy E. , Talisa Victor B. , Tang Benjamin , Thompson B. Taylor , Tsalik Ephraim L. , van der Poll Tom , van Vught Lonneke A. , Wong Hector R. , Yende Sachin , Zhao Huiying , Seymour Christopher W.
Published: February 2021

Sepsis is defined as a dysregulated host response to infection that leads to life-threatening acute organ dysfunction. It afflicts approximately 50 million people worldwide annually and is often deadly, even when evidence-based guidelines are applied promptly. Many randomized trials tested therapies for sepsis over the past 2 decades, but most have not proven beneficial. This may be because sepsis is a heterogeneous syndrome, characterized by a vast set of clinical and biologic features. Combinations of these features, however, may identify previously unrecognized groups, or “subclasses” with different risks of outcome and response to a given treatment. As efforts to identify sepsis subclasses become more common, many unanswered questions and challenges arise. These include: 1) the semantic underpinning of sepsis subclasses, 2) the conceptual goal of subclasses, 3) considerations about study design, data sources, and statistical methods, 4) the role of emerging data types, and 5) how to determine whether subclasses represent “truth.” We discuss these challenges and present a framework for the broader study of sepsis subclasses. This framework is intended to aid in the understanding and interpretation of sepsis subclasses, provide a mechanism for explaining subclasses generated by different methodologic approaches, and guide clinicians in how to consider subclasses in bedside care.
Postoperative Cerebral Oxygen Saturation in Children After Congenital Cardiac Surgery and Long-Term Total Intelligence Quotient: A Prospective Observational Study
Authors: Carra Giorgia , Flechet Marine , Jacobs An , Verstraete Sören , Vlasselaers Dirk , Desmet Lars , Van Cleemput Hanna , Wouters Pieter , Vanhorebeek Ilse , Van den Berghe Greet , Güiza Fabian , Meyfroidt Geert
Published: February 2021

OBJECTIVES:

During the early postoperative period, children with congenital heart disease can suffer from inadequate cerebral perfusion, with possible long-term neurocognitive consequences. Cerebral tissue oxygen saturation can be monitored noninvasively with near-infrared spectroscopy. In this prospective study, we hypothesized that reduced cerebral tissue oxygen saturation and increased intensity and duration of desaturation (defined as cerebral tissue oxygen saturation < 65%) during the early postoperative period, independently increase the probability of reduced total intelligence quotient, 2 years after admission to a PICU.

DESIGN:

Single-center, prospective study, performed between 2012 and 2015.

SETTING:

The PICU of the University Hospitals Leuven, Belgium.

PATIENTS:

The study included pediatric patients after surgery for congenital heart disease admitted to the PICU.

INTERVENTIONS:

None.

MEASUREMENTS AND MAIN RESULTS:

Postoperative cerebral perfusion was characterized with the mean cerebral tissue oxygen saturation and dose of desaturation of the first 12 and 24 hours of cerebral tissue oxygen saturation monitoring. The independent association of postoperative mean cerebral tissue oxygen saturation and dose of desaturation with total intelligence quotient at 2-year follow-up was evaluated with a Bayesian linear regression model adjusted for known confounders. According to a noninformative prior, reduced mean cerebral tissue oxygen saturation during the first 12 hours of monitoring results in a loss of intelligence quotient points at 2 years, with a 90% probability (posterior β estimates [80% credible interval], 0.23 [0.04–0.41]). Similarly, increased dose of cerebral tissue oxygen saturation desaturation would result in a loss of intelligence quotient points at 2 years with a 90% probability (posterior β estimates [80% credible interval], –0.009 [–0.016 to –0.001]).

CONCLUSIONS:

Increased dose of cerebral tissue oxygen saturation desaturation and reduced mean cerebral tissue oxygen saturation during the early postoperative period independently increase the probability of having a lower total intelligence quotient, 2 years after PICU admission.
Association of Standard Electroencephalography Findings With Mortality and Command Following in Mechanically Ventilated Patients Remaining Unresponsive After Sedation Interruption
Authors: Legouy Camille , Girard-Stein Laura , Wanono Ruben , de Montmollin Etienne , Vellieux Geoffroy , Bouadma Lila , Dupuis Claire , Abid Sonia , Vinclair Camille , Ruckly Stéphane , Rouvel-Tallec Anny , d’Ortho Marie-Pia , Timsit Jean-François , Sonneville Romain
Published: February 2021

Context:

Delayed awakening after sedation interruption is frequent in critically ill patients receiving mechanical ventilation.

OBJECTIVES:

We aimed to investigate the association of standard electroencephalography with mortality and command following in this setting.

Design, Setting, and Patients:

In a single-center study, we retrospectively analyzed standard electroencephalography performed in consecutive mechanically ventilated patients remaining unresponsive (comatose/stuporous or unable to follow commands) after sedation interruption. Standard electroencephalography parameters (background activity, continuity, and reactivity) were reassessed by neurophysiologists, blinded to patients’ outcome. Patients were categorized during follow-up into three groups based on their best examination as: 1) command following, 2) unresponsive, or 3) deceased. Cause-specific models were used to identify independent standard electroencephalography parameters associated with main outcomes, that is, mortality and command following. Follow-up was right-censored 30 days after standard electroencephalography.

MEASUREMENTS AND MAIN RESULTS:

Main standard electroencephalography parameters recorded in 121 unresponsive patients (median time between sedation interruption and standard electroencephalography: 2 d [interquartile range, 1–4 d]) consisted of a background frequency greater than 4 Hz in 71 (59%), a discontinuous background in 19 (16%), and a preserved reactivity in 98/120 (82%) patients. At 30 days, 66 patients (55%) were command following, nine (7%) were unresponsive, and 46 (38%) had died. In a multivariate analysis adjusted for nonneurologic organ failure, a reactive standard electroencephalography with a background frequency greater than 4 Hz was independently associated with a reduced risk of death (cause-specific hazard ratio, 0.38; CI 95%, 0.16–0.9). By contrast, none of the standard electroencephalography parameters were independently associated with command following. Sensitivity analyses conducted after exclusion of 29 patients with hypoxic brain injury revealed similar findings.

CONCLUSIONS:

In patients remaining unresponsive after sedation interruption, a pattern consisting of a reactive standard electroencephalography with a background frequency greater than 4 Hz was associated with decreased odds of death. None of the standard electroencephalography parameters were independently associated with command following.
Outcomes of Pediatric Extracorporeal Cardiopulmonary Resuscitation: A Systematic Review and Meta-Analysis
Authors: Farhat Abdelaziz , Ling Ryan Ruiyang , Jenks Christopher L. , Poon Wynne Hsing , Yang Isabelle Xiaorui , Li Xilong , Liu Yulun , Darnell-Bowens Cindy , Ramanathan Kollengode , Thiagarajan Ravi R. , Raman Lakshmi
Published: February 2021

OBJECTIVE:

The goal of this work is to provide insight into survival and neurologic outcomes of pediatric patients supported with extracorporeal cardiopulmonary resuscitation.

DATA SOURCES:

A systematic search of Embase, PubMed, Cochrane, Scopus, Google Scholar, and Web of Science was performed from January 1990 to May 2020.

STUDY SELECTION:

A comprehensive list of nonregistry studies with pediatric patients managed with extracorporeal cardiopulmonary resuscitation was included.

DATA EXTRACTION:

Study characteristics and outcome estimates were extracted from each article.

DATA SYNTHESIS:

Estimates were pooled using random-effects meta-analysis. Differences were estimated using subgroup meta-analysis and meta-regression. The Meta-analyses Of Observational Studies in Epidemiology guideline was followed and the certainty of evidence was assessed using Grading of Recommendations Assessment, Development and Evaluation system. Twenty-eight studies (1,348 patients) were included. There was a steady increase in extracorporeal cardiopulmonary resuscitation occurrence rate from the 1990s until 2020. There were 32, 338, and 1,094 patients’ articles published between 1990 and 2000, 2001 and 2010, and 2010 and 2020, respectively. More than 70% were cannulated for a primary cardiac arrest. Pediatric extracorporeal cardiopulmonary resuscitation patients had a 46% (CI 95% = 43–48%; p < 0.01) overall survival rate. The rate of survival with favorable neurologic outcome was 30% (CI 95% = 27–33%; p < 0.01).

CONCLUSIONS:

The use of extracorporeal cardiopulmonary resuscitation is rapidly expanding, particularly for children with underlying cardiac disease. An overall survival of 46% and favorable neurologic outcomes add credence to this emerging therapy.
Admission Hemoglobin Levels Are Associated With Functional Outcome in Spontaneous Intracerebral Hemorrhage
Authors: Acosta Julián N. , Leasure Audrey C. , Kuohn Lindsey R. , Both Cameron P. , Petersen Nils H. , Sansing Lauren H. , Matouk Charles C. , Testai Fernando , Langefeld Carl D. , Woo Daniel , Kamel Hooman , Murthy Santosh B. , Qureshi Adnan , Mayer Stephan A. , Sheth Kevin N. , Falcone Guido J.
Published: February 2021

OBJECTIVES:

To test the hypothesis that admission hemoglobin levels are associated with outcome in primary, nontraumatic intracerebral hemorrhage.

DESIGN:

Individual patient data meta-analysis of three studies of intracerebral hemorrhage.

SETTING:

Two randomized clinical trials and one multiethnic observational study.

PATIENTS:

Patients with spontaneous, nontraumatic intracerebral hemorrhage.

INTERVENTIONS:

None.

MEASUREMENTS AND MAIN RESULTS:

Our exposure of interest was admission hemoglobin levels and the primary outcome was 3-month postintracerebral hemorrhage-dichotomized modified Rankin Scale (0–3 vs 4–6). Intermediate outcomes were admission hematoma volume and hematoma expansion defined as 6 mL or 33% increase in hemorrhage size on repeat CT. A total of 4,172 intracerebral hemorrhage patients were included in the study (mean age 63 [sd = 14]; female sex 1,668 [40%]). Each additional g/dL of admission hemoglobin was associated with 14% (odds ratio, 0.86; 95% CI, 0.82–0.91) and 7% (odds ratio, 0.93; 95% CI, 0.88–0.98) reductions in the risk of poor outcome in unadjusted and adjusted analyses, respectively. Dose-response analyses indicated a linear relationship between admission hemoglobin levels and poor outcome across the entire evaluated range (test-for-trend p < 0.001). No consistent associations were found between the admission hemoglobin levels and hematoma volume or hematoma expansion.

CONCLUSIONS:

Higher hemoglobin levels are associated with better outcome in intracerebral hemorrhage. Further research is needed to evaluate admission hemoglobin levels as both a therapeutic target and predictor of outcome.
Identification of HLA-A*0201-restricted CTL Epitopes for MLAA-34-specific Immunotherapy for Acute Monocytic Leukemia
Authors: Bai Ju , Wang Jianli , Yang Yun , Wang Fangxia , He Aili , Zhang Wanggang
Published: February 2021

Our previous research has shown that monocytic leukemia–associated antigen-34 (MLAA-34) was a novel antiapoptotic molecule with unique expression in acute monocytic leukemia (M5), making it an ideal target for T-cell–based immunotherapy. Here, we sought to identify HLA-A*0201-restricted cytotoxic T-lymphocyte (CTL) epitope of MLAA-34 by reverse immunology. In all, 10 HLA-A*0201 restricted epitopes of MLAA-34 were predicted by bioinformatics. MLAA-34324–332, MLAA-34293–301, and MLAA-34236–244 showed the strongest HLA-A*0201-binding affinity. The percentages of HLA-A*0201-MLAA-34236–244 tetramer+ CD8+ T cells in MLAA-34236–244-induced CTLs were raised apparently. Enzyme-linked immunospot showed that MLAA-34236–244 and MLAA-34324–332-specific CTLs produced a higher amount of interferon-γ. MLAA-34236–244-induced CTLs presented a stronger cytotoxic effect on THP-1 cells (HLA-A*0201+MLAA-34+) at various effector to target ratios. MLAA-34236–244 peptide vaccine could inhibit the tumor growth and improve mean survival time of leukemia-bearing human peripheral blood lymphocyte reconstituting severe combined immunodeficient mice. Mice immunized with MLAA-34236–244 vaccine had increased percentages of MLAA-34236–244 tetramer+ CD8+ T cells in the spleen after each round of immunization. High-purity CD8+ and CD4+ T cells were sorted by Dynabeads as effector cells. The killing activity of CD8+ T cells was higher than that of CD4+ T cells. CTLs derived from the MLAA-34 peptide vaccine group were significantly higher than other therapeutic groups and showed specific cytotoxicity to THP-1 cells. Increased interferon-γ and interleukin (IL)-2 and decreased IL-10 and IL-4 were seen in the MLAA-34236–244 peptide vaccine group. MLAA-34236–244 peptide (ILDRHNFAI) is an effective HLA-A*0201-restricted CTL epitope and that it may serve as a promising strategy in designing antigen-specific immunotherapy against MLAA-34-positive acute monocytic leukemia.
Myasthenia Symptom Burden, Fatigue, and Sleep: Are They Related?
Authors: Yang Sarah , Miglis Mitchell G. , Jaradeh Safwan , Muppidi Srikanth
Published: February 2021

Objective:

Our aim is to explore the relationship between myasthenia gravis (MG)-related symptom burden, sleep quality, and fatigue in a diverse group of self-identified MG patients.

Methods:

Patients provided relevant myasthenia disease data and completed the MG QOL-15, Epworth sleepiness scale, Pittsburgh Sleep Quality Index, and fatigue severity score (FSS) online. MG activities of daily living scale (MG-ADL) was completed on a follow-up telephone interview.

Results:

One hundred ninety-six patients completed the online survey and 99 provided MG-ADL data. The mean age was 52 ± 15.34 years, 88 were acetylcholine receptor antibody positive, and 21 were muscle specific kinase positive. The mean MG-ADL was 6.81, indicating a moderate MG disease burden. Forty-seven (24%) reported high Epworth sleepiness scale scores, 152 (77%) reported high Pittsburgh Sleep Quality Index scores, and 162 (82%) reported high FSS scores. Correlation analysis correcting for body mass index and sleep apnea revealed a moderate positive correlation between MGQOL-15, MG-ADL, and FSS.

Conclusions:

There is a moderate positive correlation between various MG-specific outcome measures and fatigue severity.