bluuebunny/crossref_metadata_2025 huggingface dataset:
Diagnostic Bedside Ultrasound Program Development in Pediatric Critical Care Medicine: Results of a National Survey*
Authors: Conlon Thomas W. , Kantor David B. , Su Erik R. , Basu Sonali , Boyer Donald L. , Haileselassie Bereketeab , Petersen Tara L. , Su Felice , Nishisaki Akira
Published: August 2018

Objectives:

To assess current diagnostic bedside ultrasound program core element (training, credentialing, image storage, documentation, and quality assurance) implementation across pediatric critical care medicine divisions in the United States.

Design:

Cross-sectional questionnaire-based needs assessment survey.

Setting:

Pediatric critical care medicine divisions with an Accreditation Council of Graduate Medical Education-accredited fellowship.

Respondents:

Divisional leaders in education and/or bedside ultrasound training.

Interventions:

None.

Measurements and Main Results:

Fifty-five of 67 pediatric critical care medicine divisions (82%) with an Accreditation Council of Graduate Medical Education-accredited fellowship provided responses. Overall, 63% of responding divisions (34/54) were clinically performing diagnostic bedside ultrasound studies with no difference between divisions with large versus small units. Diagnostic bedside ultrasound training is available for pediatric critical care medicine fellows within 67% of divisions (35/52) with no difference in availability between divisions with large versus small units. Other core elements were present in less than 25% of all divisions performing clinical studies, with a statistically significant increase in credentialing and documentation among divisions with large units (p = 0.048 and 0.01, respectively). All core elements were perceived to have not only high impact in program development but also high effort in implementation. Assuming that all structural elements could be effectively implemented within their division, 83% of respondents (43/52) agreed that diagnostic bedside ultrasound should be a core curricular component of fellowship education.

Conclusions:

Diagnostic bedside ultrasound is increasingly prevalent in training and clinical use across the pediatric critical care medicine landscape despite frequently absent core programmatic infrastructural elements. These core elements are perceived as important to program development, regardless of division unit size. Shared standardized resources may assist in reducing the effort in core element implementation and allow us to measure important educational and clinical outcomes.
The Association Between the Functional Status Scale and the Pediatric Functional Independence Measure in Children Who Survive Traumatic Brain Injury*
Authors: Maddux Aline B. , Cox-Martin Matthew , Dichiaro Michael , Bennett Tellen D.
Published: August 2018

Objectives:

To determine the association between the Functional Status Scale and Pediatric Functional Independence Measure scores during the rehabilitation stay in children who survive traumatic brain injury.

Design:

Secondary analysis of a prospective observational cohort study.

Setting:

Tertiary care children’s hospital with a level 1 trauma center and inpatient rehabilitation service.

Patients:

Sixty-five children less than 18 years old admitted to an ICU with acute traumatic brain injury and subsequently transferred to the inpatient rehabilitation service.

Interventions:

Not applicable.

Measurements and Main Results:

Functional Status Scale and Pediatric Functional Independence Measure at transfer to rehabilitation and Pediatric Functional Independence Measure at discharge from rehabilitation. The median age of the cohort was 7.1 years (interquartile range, 0.8–12.3 yr), and 29% were female. Nearly all of the children were healthy prior to the traumatic brain injury: six patients (9.2%) had a baseline Functional Status Scale score greater than 6. At the time of transfer to inpatient rehabilitation, total Functional Status Scale and Pediatric Functional Independence Measure scores had the expected negative correlation due to increasing disability resulting in lower scores in Pediatric Functional Independence Measure and higher scores in Functional Status Scale (r = –0.49; 95% CI, –0.62 to –0.35). Among subjects with less disability as measured by lower total Functional Status Scale scores, we found substantial variability in the total Pediatric Functional Independence Measure scores. In contrast, Pediatric Functional Independence Measure scores were consistently low among subjects with a wide range of higher total Functional Status Scale scores (more disability).

Conclusions:

Although proprietary and more time-intensive, the Pediatric Functional Independence Measure has advantages relative to the Functional Status Scale for less severely injured patients and task-specific measurements. The Functional Status Scale may have advantages relative to the Pediatric Functional Independence Measure for more severely injured patients. Further investigations are needed to characterize changes in the Functional Status Scale during the rehabilitation stay and after discharge.
Pulmonary Alveolar Proteinosis in Hereditary and Autoimmune Forms With 2 Cases
Authors: Sirin Kose Seda , Asilsoy Suna , Uzuner Nevin , Karaman Ozkan , Ozer Erdener , Anal Ozden
Published: August 2018

Pulmonary alveolar proteinosis (PAP) is a respiratory pathology characterized by the accumulation and increase of surfactant-derived material in the lungs. In clinical practice, PAP may present as the primary form, which includes autoimmune and hereditary PAP, or as the secondary form. Diffuse alveolar radiopacities on chest x-ray and the crazy-paving pattern on high-resolution computed tomography are important, although not specific findings for PAP. Bronchoalveolar lavage biopsy is a diagnostic method, and whole-lung lavage remains the criterion standard for the treatment of PAP. Evidence is required regarding treatment with exogenous anti–granulocyte/macrophage colony-stimulating factor.

Here, we present a 13-year-old male patient with hereditary PAP and a 15-year-old female patient with autoimmune PAP who presented with complaints of easy fatigability and weakness to emphasize the importance of keeping in mind PAP as a differential diagnosis in patients with respiratory failure findings.
Hypothermia
Authors: Kasmire Kathryn E. , Vega Carolina , Bennett Nicholas J. , Laurich V. Matt
Published: August 2018

Objectives

Diagnosis of sepsis in young infants can be challenging due to the nonspecific signs, which can include hypothermia. Whether the presence of hypothermia in young infants should prompt evaluation for serious infection is unclear. The objectives were to measure the prevalence of serious infection among infants ≤60 days of age with hypothermia in the emergency department (ED) and determine other clinical features of hypothermic infants who have serious infection.

Methods

This is a retrospective analysis of all infants ≤60 days seen in a children's hospital ED from April 2014 to February 2017. Primary outcome was presence of serious infection, defined as urinary tract infection, bacteremia, meningitis, pneumonia, or herpes virus infection. Hypothermia was defined as a rectal temperature of 36.0°C or less.

Results

Of 4797 infants ≤60 days of age seen in the ED, 116 had hypothermia. The prevalence of serious infection was 2.6% (3/116) in hypothermic infants compared with 15.2% (61/401) in febrile infants (P < 0.01). Hypothermic infants with serious infections were more likely to have a history of prematurity, apnea, poor feeding, lethargy, ill-appearance, and respiratory signs than hypothermic infants without serious infection. All 3 hypothermic infants with serious infection had other concerning features.

Conclusions

The prevalence of serious infection in hypothermic young infants in the ED is low. Serious infection is unlikely in infants with isolated hypothermia.
Combined Carpal Tunnel Release and Palmar Fasciectomy for Dupuytren’s Contracture Does Not Increase the Risk for Complex Regional Pain Syndrome
Authors: Loewenstein Scott N. , Duquette Stephen P. , Adkinson Joshua M.
Published: August 2018

Background:

Hand surgery dogma suggests that simultaneous surgical treatment of carpal tunnel syndrome and Dupuytren’s contracture results in an increased incidence of complex regional pain syndrome. As a result, many surgeons do not perform surgery for the two conditions concurrently. The authors’ goal was to determine the extent of this association.

Methods:

The authors identified all patients undergoing surgical treatment for carpal tunnel syndrome, Dupuytren’s contracture, or both between April of 1982 and March of 2017 using the Indiana Network for Patient Care, a large, multi-institutional, statewide information exchange. Demographics, comorbidities, and 1-year postoperative incidence of complex regional pain syndrome were recorded.

Results:

A total of 51,739 patients (95.6 percent) underwent carpal tunnel release only, 2103 (3.9 percent) underwent palmar fasciectomy only, and 305 (0.6 percent) underwent concurrent carpal tunnel release and palmar fasciectomy. There was no difference in the likelihood of developing complex regional pain syndrome (p = 0.163) between groups. Independent risk factors for developing complex regional pain syndrome were younger age; anxiety; depression; epilepsy; gout; and history of fracture of the radius, ulna, or carpus.

Conclusions:

Concurrent carpal tunnel release and palmar fasciectomy is not associated with an increased risk for developing complex regional pain syndrome. Patient demographics, medical comorbidities, and a history of upper extremity trauma are associated with the development of complex regional pain syndrome after surgery and should be discussed preoperatively as potential risk factors.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, III.
Validity of the Tinel Sign and Prevalence of Tibial Nerve Entrapment at the Tarsal Tunnel in Both Diabetic and Nondiabetic Subjects: A Cross-Sectional Study
Authors: Rinkel Willem D. , Castro Cabezas Manuel , van Neck Johan W. , Birnie Erwin , Hovius Steven E. R. , Coert J. Henk
Published: August 2018

Background:

Nerve entrapments like carpal tunnel syndrome are more prevalent in patients with diabetes, especially in those with diabetic polyneuropathy. Our study aims were to investigate the validity of the Tinel sign in diagnosing tibial neuropathy and determine the prevalence of tibial nerve entrapment in both a diabetic and nondiabetic population.

Methods:

Two hundred forty nonneuropathic subjects with diabetes and 176 diabetic subjects with neuropathy participating in the prospective Rotterdam Diabetic Foot Study and 196 reference subjects without diabetes and without neuropathy complaints were evaluated. All subjects underwent sensory testing of the feet, and complaints were assessed using the Michigan Neuropathy Screening Instrument. The Tinel sign was defined as discriminative and valid for diagnosing tibial nerve entrapment when the nerve-related Michigan Neuropathy Screening Instrument subscore of neuropathic symptoms differed at least 5 percent between the Tinel-positive and Tinel-negative subjects. When the sign was valid, prevalence estimates of tibial nerve entrapment at the tarsal tunnel were calculated.

Results:

Significantly more neuropathic symptoms (p < 0.002) and higher sensory thresholds (p < 0.0005) were observed in (compressed) tibial nerve–innervated areas, indicating that a positive Tinel sign at the tarsal tunnel is a valid measure of tibial nerve abnormality. The prevalence of tibial nerve entrapment in diabetic patients was 44.9 percent (95 percent CI, 40.1 to 49.7 percent) versus 26.5 percent (95 percent CI, 20.3 to 32.7 percent) in healthy controls (p < 0.0001).

Conclusions:

Tibial nerve entrapment is more prevalent in diabetic subjects than in controls. The significantly more frequently reported neuropathic complaints and concomitant sensory disturbances provide evidence for the role of superimposed entrapment neuropathy in diabetes-related neuropathy.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Diagnostic, IV.
Intracranial Volume and Head Circumference in Children with Unoperated Syndromic Craniosynostosis
Authors: Breakey Richard William Francis , Knoops Paul G. M. , Borghi Alessandro , Rodriguez-Florez Naiara , O’Hara Justine , James Gregory , Dunaway David J. , Schievano Silvia , Jeelani N. U. Owase
Published: August 2018

Background:

When analyzing intracranial volume gain resulting from operative intervention in craniosynostosis, it is necessary to understand the underlying growth. The authors sought to create comprehensive intracranial volume and occipitofrontal circumference growth charts, as measured on unoperated craniosynostotic children, and aimed to investigate whether intracranial volume and occipitofrontal circumference could act as proxy measures for each other.

Methods:

All preoperative Great Ormond Street Hospital patients with a diagnosis of Apert, Crouzon-Pfeiffer, or Saethre-Chotzen syndrome from the year 2004 onward were considered for this study. A control group of unaffected Great Ormond Street Hospital patients were also measured. Intracranial volume and occipitofrontal circumference were measured on the same scans. To study correlation between intracranial volume and occipitofrontal circumference, logarithmic fits were assessed.

Results:

One hundred forty-seven craniosynostotic children with 221 preoperative scans were included (81 Apert, 81 Crouzon, 31 Pfeiffer, and 28 Saethre-Chotzen). The control group comprised 56 patients with 58 scans. Apert intracranial volume curves were significantly larger than those of other syndromes from 206 days onward; occipitofrontal circumference curves were not significantly different. The correlation coefficient between intracranial volume and occipitofrontal circumference was R
2 = 0.87 for all syndromes combined and R
2 = 0.91 for the control group.

Conclusions:

Apert syndrome children have a larger intracranial volume than children with other syndromic craniosynostotic conditions and unaffected children but maintain a similar occipitofrontal circumference. This study demonstrates high correlation between intracranial volume and occipitofrontal circumference with clinical care implications. The authors’ reference growth curves can be used to monitor intracranial volume change over time and correct operative change for underlying growth.
Vascular Endothelial Growth Factor Enhances Proliferation of Human Tenocytes and Promotes Tenogenic Gene Expression
Authors: Kraus Armin , Sattler Daniel , Wehland Markus , Luetzenberg Ronald , Abuagela Nauras , Infanger Manfred
Published: August 2018

Background:

In obtaining human tenocytes for tendon tissue engineering, a low proliferation rate and phenotype loss during passaging is a problem. It was the authors’ aim to evaluate the influence of vascular endothelial growth factor (VEGF) on human tenocyte growth and gene expression.

Methods:

Human tenocytes were exposed to human VEGF in various concentrations (5, 10, and 20 ng/ml) for 5 days. Cell proliferation was counted and expression of tendon-related genes was analyzed.

Results:

Tenocyte count was 1.4 × 105/ml, 2.7 × 105/ml, 2.3 × 105/ml, and 3.7 × 105/ml for 0, 5, 10, and 20 ng/ml VEGF, respectively. Expression ofCol1was up-regulated 6.4 ± 4.2-fold, 60.1 ± 21.6-fold, and 15.8 ± 10.2-fold for 5, 10, and 20 ng/ml VEGF; all differences were significant withp< 0.05.Col3was down-regulated to 0.2 ± 0.1-fold, 0.3 ± 0.1-fold, and 0.1 ± 0.03-fold for 5, 10, and 20 ng/ml VEGF; all differences were significant.Elnwas up-regulated 2.3 ± 1.7-fold, 25.5 ± 10.9-fold, and 16.6 ± 9.0-fold for 5, 10, and 20 ng/ml VEGF; differences were significant for 10 and 20 ng/ml VEGF.TSCwas down-regulated to 0.3 ± 0.1-fold and 0.3 ± 0.1-fold for 5 and 20 ng/ml VEGF; differences were significant for 5 and 20 ng/ml.SCXwas up-regulated to 31.3 ± 8.5-fold, 49.1 ± 23.4-fold, and 20.9 ± 9.5-fold for 5, 10, and 20 ng/ml VEGF; all changes were significant.

Conclusions:

VEGF enhances proliferation and expression of tendon-related genes in human tenocytes. It could therefore be a useful addition for tenocyte cultivation.
Comparison of Treatment Rates of Depression After Stroke Versus Myocardial Infarction: A Systematic Review and Meta-Analysis of Observational Data
Authors: Ladwig Simon , Zhou Zien , Xu Ying , Wang Xia , Chow Clara K. , Werheid Katja , Hackett Maree L.
Published: August 2018

Objective

Depression after stroke and myocardial infarction (MI) is common but often assumed to be undertreated without reliable evidence being available. Thus, we aimed to determine treatment rates and investigate the application of guidelines in these conditions.

Methods

Databases MEDLINE, EMBASE, PsycInfo, Web of Science, CINAHL, and Scopus were systematically searched without language restriction from inception to June 30, 2017. Prospective observational studies with consecutive recruitment reporting any antidepressant treatment in adults with depression after stroke or MI were included. Random-effects models were used to calculate pooled estimates of treatment rates.

Results

Fifty-five studies reported 32 stroke cohorts (n = 8938; pooled frequency of depression = 34%, 95% confidence interval [CI] = 29%–38%) and 17 MI cohorts (n = 10,767; pooled frequency of depression = 24%, 95% CI = 20%–28%). In 29 stroke cohorts, 24% (95% CI = 20%–27%) of 2280 depressed people used antidepressant medication. In 15 MI cohorts, 14% (95% CI = 8%–19%) of 2381 depressed people used antidepressant medication indicating a lower treatment rate than in stroke. Two studies reported use of psychosocial interventions, indicating that less than 10% of participants were treated.

Conclusions

Despite the high frequency of depression after stroke and MI and the existence of efficacious treatment strategies, people often remain untreated. Innovative strategies are needed to increase the use of effective antidepressive interventions in patients with cardiovascular disease.
Quantifying Lymph Nodes During Lymph Node Transplantation
Authors: Tran Bao Ngoc N. , Celestin Arthur R. , Lee Bernard T. , Critchlow Jonathan , Tsai Leo , Toskich Beau , Singhal Dhruv
Published: August 2018

Quantifying lymph nodes in vascularized lymph node transfer (VLNT) has been performed using preoperative percutaneous ultrasound. The higher resolution and accuracy of intraoperative ultrasound (IOUS) over transcutaneous ultrasound has been demonstrated in the radiology literature for the identification and characterization of finer structures including hepatic lesions, pancreatic lesions, and biliary or pancreatic ducts. We hypothesize that IOUS during VLNT would be a superior method to quantify and map lymph nodes in our flaps. A prospectively collected database of patients undergoing VLNT over 3 years (October 2014 to October 2017) was reviewed. Patients who underwent IOUS during flap harvest, before pedicle ligation to simultaneously map and quantify the number of lymph nodes were included in the study. Twenty-one patients with an average age of 58.7 years and a mean BMI of 32.3 underwent VLNT with IOUS for chronic lymphedema during the study period. Extremity lymphedema was classified as Campisi IB (n = 7), IIA (n = 7), IIB (n = 5), and IIIA (n = 2). There were 14 superficial circumflex iliac artery flaps, including 4 performed concomitantly with a deep inferior epigastric perforator flap, 1 transverse cervical artery flap, and 6 omental flaps. The average number of lymph nodes transferred per IOUS was 4.3 for superficial circumflex iliac artery flaps, 4 for the transverse cervical artery flap, and 5.2 for the omental flaps. Intraoperative ultrasound allows the lymphatic surgeon to precisely map the location of lymph nodes which can guide intraoperative decision making. As there is no data correlating the number of lymph nodes transferred and outcomes after VLNT, developing a precise intraoperative quantification method is important.
Lower Eyelid Reconstruction Using a Nasolabial, Perforator-based V-Y Advancement Flap
Authors: Gibreel Waleed , Harvey Jamison Anne , Garrity James , Bite Uldis
Published: August 2018

Background

Reconstruction of the lower eyelid represents a unique challenge to the reconstructive surgeon. Studies evaluating the utility of the nasolabial V-Y advancement flap in lower eyelid reconstruction are limited and techniques to optimize outcomes following eyelid reconstruction with this technique are not well described. We seek to evaluate our experience and outcomes with lower eyelid reconstruction using the nasolabial perforator-based V-Y advancement flap.

Methods

After institutional review board approval, medical charts of all patients who underwent lower eyelid reconstruction using the nasolabial perforator-based V-Y advancement flap between February 2013 and October 2017 were reviewed. Data regarding etiology, location of the lesion, lower eyelid defect, methods of reconstruction, postoperative complications, and follow up duration were collected and analyzed.

Results

Over the study period, 5 patients (3 male) underwent lower eyelid reconstruction after oncologic resection of melanoma (n = 1) and nonmelanoma (n = 4) skin cancer using the nasolabial perforator-based V-Y advancement flap at a mean age of 69 years (range, 56–82 years). Median follow-up duration was 5.9 months (interquartile range, 2.25–25.9). A mean of 5.4 (range, 2–10) perforators were included in the initial flap design. After completion of flap dissection and perforator division, a mean of 4.4 (range, 2–7) perforators were preserved and included in the flap. All flaps demonstrated clinical viability with no cases of partial or total flap loss. One patient developed an asymptomatic ectropion during the follow-up period.

Conclusions

The nasolabial, perforator-based V-Y advancement flap is a reliable reconstructive method for lower eyelid defects.
A Simple and Reliable Submental Intubation Technique for Maxillofacial Fractures
Authors: Oshima Naoya , Shiraishi Tomohiro , Kawauchi Tsukasa , Oba Jun , Sato Daisuke , Fujiki Masahide , Ozaki Mine , Takushima Akihiko , Harii Kiyonori
Published: August 2018

In 1986, Altemir first reported the use of submental intubation to avoid tracheotomy in patients with panfacial and midfacial fractures for whom intermaxillary fixation is necessary, but orotracheal and nasotracheal intubations are not recommended. This novel technique allowed intraoperative access to perform dental occlusion and reconstruction of the nasal pyramid in patients with skull base fractures. Herein, we describe a refined technique based on Altemir's original procedure. Seven male patients with panfacial fractures underwent submental intubation using our refined technique. The technique was developed after encountering a technical error with Altemir's original procedure. In this new technique, we employed a 2-0 silk suture guide to allow the passage of both the endotracheal and cuff-inflation tubes through the same tunnel created from the oral cavity to the submental area. The success rate of the refined technique was 100%, and there were no intraoperative or postoperative complications. There was 20 seconds of ventilation outage time in total. Endotracheal and cuff-inflation tubes were easily and quickly passed through the same submental tunnel. Our refined technique is simple, easy, safe, fast, inexpensive, and does not require specific materials. Submental scars were smaller and relatively inconspicuous in this study, compared to those reportedly associated with other modified techniques.
Comparison of Mechanical Stabilization of the Mandibular Angulus Fracture Fixation, With Titanium Plates and Screws, Resorbable Plates and Screws, and Bone Adhesives
Authors: Cural Ülkem , Atalay Berkem , Yildirim Mustafa Sami
Published: August 2018

Mandibular fractures mostly occur at the angulus mandibula with a concurrent symphysis or corpus fracture on the opposite side. Misapplication can damage the nerves, adjacent teeth, soft tissues, and result in permanent tooth germs. In children, growth centers can be damaged, and this may result in asymmetry and retardation in growth and development. The aim of this study was to compare the mechanical stabilization after different techniques were used to create the mandibular angle fracture fixation and to create oblique fractures at mandible angles. This study included 32 hemi-mandibles that were divided into 4 groups with 8 units per group. All of the hemi-mandibles were fixated using different techniques; titanium mini plates and screws, resorbable mini plate and screws, and resorbable mini plates and cyanoacrylate bone adhesive only. The fixated mandibles were tested under molar masticatory forces, and their stabilization endurance was assessed. There were no significant differences in titanium mini plaque screw and resorbable plaque screw techniques under 40 N force. Resorbable and titanium plates and screws did not have any advantage over each other in terms of biomechanical behaviors. It is suitable to use adhesives in the reduction of complicated but nonload-bearing areas. The adhesive used in this study can adhere to the bone but should be further evolved for clinical use.
Renal Resistive Index: Response to Shock and its Determinants in Critically Ill Patients
Authors: Rozemeijer Sander , Haitsma Mulier Jelle L.G. , Röttgering Jantine G. , Elbers Paul W.G. , Spoelstra-de Man Angélique M.E. , Tuinman Pieter Roel , de Waard Monique C. , Oudemans-van Straaten Heleen M.
Published: August 2018

Introduction:

Shock is characterized by micro- and macrovascular flow impairment contributing to acute kidney injury (AKI). Routine monitoring of the circulation regards the macrocirculation but not the renal circulation which can be assessed with Doppler ultrasound as renal resistive index (RRI). RRI reflects resistance to flow. High RRI predicts persistent AKI. Study aims were to determine whether RRI is elevated in shock and to identify determinants of RRI.

Materials and Methods:

This prospective observational cohort study included two cohorts of patients, with and without shock less than 24-h after intensive care admission. Apart from routine monitoring, three study measurements were performed simultaneously: RRI, sublingual microcirculation, and bioelectral impedance analysis.

Results:

A total of 92 patients were included (40 shock, 52 nonshock), median age was 69 [60–76] vs. 67 [59–76], P = 0.541; APACHE III was 87 [65–119] vs. 57 [45–69], P < 0.001. Shock patients had higher RRI than patients without shock (0.751 [0.692–0.788] vs. 0.654 [0.610–0.686], P < 0.001). Overall, high age, APACHE III score, lactate, vasopressor support, pulse pressure index (PPI), central venous pressure (CVP), fluid balance, and low preadmission estimated glomerular filtration rate, mean arterial pressure (MAP), creatinine clearance, and reactance/m were associated with high RRI at univariable regression (P < 0.01). Microcirculatory markers were not. At multivariable regression, vasopressor support, CVP, PPI and MAP, reactance/m, and preadmission eGFR were independent determinants of RRI (n = 92, adj. R
2 = 0.587).

Conclusions:

Patients with shock have a higher RRI than patients without shock. Independent determinants of high RRI were pressure indices of the systemic circulation, low membrane capacitance, and preadmission renal dysfunction. Markers of the sublingual microcirculation were not.
Remote Photoplethysmographic Assessment of the Peripheral Circulation in Critical Care Patients Recovering From Cardiac Surgery
Authors: Rasche Stefan , Trumpp Alexander , Schmidt Martin , Plötze Katrin , Gätjen Frederik , Malberg Hagen , Matschke Klaus , Rudolf Matthias , Baum Fabian , Zaunseder Sebastian
Published: August 2018

Purpose:

Camera-based photoplethysmography (cbPPG) remotely detects the volume pulse of cardiac ejection in the peripheral circulation. The cbPPG signal is sourced from the cutaneous microcirculation, yields a 2-dimensional intensity map, and is therefore an interesting monitoring technique. In this study, we investigated whether cbPPG is in general sufficiently sensitive to discern hemodynamic conditions.

Methods:

cbPPG recordings of 70 patients recovering from cardiac surgery were analyzed. Photoplethysmograms were processed offline and the optical pulse power (OPP) of cardiac ejection was calculated. Hemodynamic data, image intensity, and patient movements were recorded synchronously. The effects of hemodynamic parameters and measurement conditions on the patient's individual OPP variability and their actual OPP values were calculated in mixed-effects regression models.

Results:

Mean arterial pressure (MAP), pulse pressure (PP), heart rate (HR), and central venous pressure (CVP) significantly explained the individual OPP variability. PP had the highest explanatory power (19.9%). Averaged OPP significantly increased with PP and MAP (P < 0.001, respectively) and decreased with higher HR (P = 0.024). CVP had a 2-directional, nonsignificant effect on averaged OPP. Image intensity and patient movements did significantly affect OPP. After adjustment for hemodynamic covariables and measurement conditions, the effect of PP and HR remained unchanged, whereas that of MAP vanished.

Conclusion:

cbPPG is sensitive to hemodynamic parameters in critical care patients. It is a potential application for monitoring the peripheral circulation. Its value in a clinical setting has to be determined.
Chemogenetic restoration of autonomous subthalamic nucleus activity ameliorates Parkinsonian motor dysfunction
Authors: McIver Eileen L. , Chu Hong-Yuan , Atherton Jeremy F. , Cosgrove Kathleen E. , Kondapalli Jyothisri , Wokosin David , Surmeier D. James , Mark D.Bevan
Published: August 2018

Highlights

decorrelating autonomous STN activity was downregulated in both toxin and genetic models of PD

elevation of D2-striatal projection neuron transmission was sufficient for downregulation

downregulation was dependent on activation of STN NMDA receptors and KATP channels

chemogenetic restoration of autonomous spiking reduced synaptic patterning of STN neurons and PD motor dysfunction

eToC

Excessive synaptic synchronization of STN activity is linked to the symptomatic expression of PD.McIver and colleagues describe the cellular and circuit mechanisms responsible for the loss of decorrelating autonomous STN activity in PD models and demonstrate that chemogenetic rescue of autonomous spiking reduces synaptically patterned STN activity and ameliorates Parkinsonian motor dysfunction.

Excessive, synaptically-driven synchronization of subthalamic nucleus (STN) neurons is widely thought to contribute to akinesia, bradykinesia, and rigidity in Parkinson’s disease (PD). Electrophysiological, optogenetic, chemogenetic, genetic, 2-photon imaging, and pharmacological approaches revealed that the autonomous activity of STN neurons, which opposes synaptic synchronization, was downregulated in both toxin and genetic mouse models of PD.Loss of autonomous spiking was due to increased transmission of D2-striatal projection neurons, leading in the STN to elevated activation of NMDA receptors and generation of reactive oxygen species that promoted KATP channel opening.Chemogenetic restoration of autonomous firing in STN neurons reduced synaptic patterning and ameliorated Parkinsonian motor dysfunction, arguing that elevating intrinsic STN activity is an effective therapeutic intervention in PD.
A transformation of oxygen saturation (the saturation virtual shunt) to improve clinical prediction model calibration and interpretation
Authors: Zhou Guohai , Karlen Walter , Brant Rollin , Wiens Matthew , Kissoon Niranjan , Ansermino J Mark
Published: August 2018

Background

The relationship between peripheral oxygen saturation (SpO2) and the inspired oxygen concentration is non-linear. SpO2 is frequently used as a dichotomized predictor, to manage this non-linearity. We propose the saturation virtual shunt (VS) as a transformation of SpO2 to a continuous linear variable to improve interpretation of disease severity within clinical prediction models.

Method

We calculate the saturation VS based on an empirically derived approximation formula between physiological VS and SpO2. We evaluated the utility of the saturation VS in a clinical study predicting the need for facility admission in children in a low resource health-care setting.

Results

The transformation was saturation VS = 68.864*log10(103.711 − SpO2) −52.110. The ability to predict hospital admission based on a dichotomized SpO2 produced an area under the receiver operating characteristic curve of 0.57, compared to 0.71 based on the untransformed SpO2 and saturation VS. However, the untransformed SpO2 demonstrated a lack of fit compared to the saturation VS (goodness-of-fit test p-value <0.0001 versus 0.098). The observed admission rates varied non-linearly with the untransformed SpO2 but varied linearly with the saturation VS.

Conclusion

The saturation VS estimates a continuous linearly interpretable disease severity based on SpO2 and improves clinical prediction.
Appearance of synthetic vector-associated antibiotic resistance genes in next-generation sequences
Authors: Taiaroa George , Cook Gregory M. , Williamson Deborah A
Published: August 2018

Synopsis

Background

Next-generation sequencing methods have broad application in addressing increasing antibiotic resistance, with identification of antibiotic resistance genes (ARGs) having direct clinical relevance.

Objectives

Here, we describe the appearance of synthetic vector-associated ARGs in major public next-generation sequence data sets and assemblies, including in environmental samples and high priority pathogenic microorganisms.

Methods

A search of selected databases – the National Centre for Biotechnology Information (NCBI) nucleotide collection, NCBI whole genome shotgun sequence contigs and literature-associated European Nucleotide Archive (ENA) datasets, was carried out using sequences characteristic of pUC-family synthetic vectors as a query in BLASTn. Identified hits were confirmed as being of synthetic origin, and further explored through alignment and comparison to primary read sets.

Results

Synthetic vectors are attributed to a range of organisms in each of the NCBI databases searched, including examples belonging to each Kingdom of life. These synthetic vectors are associated with various ARGs, primarily those encoding resistance to beta-lactam antibiotics and aminoglycosides. Synthetic vector associated ARGs are also observed in multiple environmental meta-transcriptome datasets, as shown through analysis of associated ENA primary reads, and are proposed to have led to incorrect statements being made in the literature on the abundance of ARGs.

Conclusions

Appearance of synthetic vector-associated ARGs can confound the study of antimicrobial resistance in varied settings, and may have clinical implications in the nearfuture.
High-throughput amplicon sequencing of the full-length 16S rRNA gene with single-nucleotide resolution
Authors: Callahan Benjamin J , Wong Joan , Heiner Cheryl , Oh Steve , Theriot Casey M , Gulati Ajay S , McGill Sarah K , Dougherty Michael K
Published: August 2018

Targeted PCR amplification and high-throughput sequencing (amplicon sequencing) of 16S rRNA gene fragments is widely used to profile microbial communities. New long-read sequencing technologies can sequence the entire 16S rRNA gene, but higher error rates have limited their attractiveness when accuracy is important. Here we present a high-throughput amplicon sequencing methodology based on PacBio circular consensus sequencing and the DADA2 sample inference method that measures the full-length 16S rRNA gene with single-nucleotide resolution and a near-zero error rate.

In two artificial communities of known composition, our method recovered the full complement of full-length 16S sequence variants from expected community members without residual errors. The measured abundances of intra-genomic sequence variants were in the integral ratios expected from the genuine allelic variants within a genome. The full-length 16S gene sequences recovered by our approach allowedE. colistrains to be correctly classified to the O157:H7 and K12 sub-species clades. In human fecal samples, our method showed strong technical replication and was able to recover the full complement of 16S rRNA alleles in severalE. colistrains.

There are likely many applications beyond microbial profiling for which high-throughput amplicon sequencing of complete genes with single-nucleotide resolution will be of use.
Breathing coordinates limbic network dynamics underlying memory consolidation
Authors: Karalis Nikolaos , Sirota Anton
Published: August 2018

The coordinated activity between remote brain regions underlies cognition and memory function. Although neuronal oscillations have been proposed as a mechanistic substrate for the coordination of information transfer and memory consolidation during sleep, little is known about the mechanisms that support the widespread synchronization of brain regions and the relationship of neuronal dynamics with other bodily rhythms, such as breathing. Here we address this question using large-scale recordings from a number of structures, including the medial prefrontal cortex, hippocampus, thalamus, amygdala and nucleus accumbens in mice. We identify a dual mechanism of respiratory entrainment, in the form of an intracerebral corollary discharge that acts jointly with an olfactory reafference to coordinate limbic network dynamics, such as hippocampal ripples and cortical UP and DOWN states, involved in memory consolidation. These results highlight breathing, a perennial rhythmic input to the brain, as an oscillatory scaffold for the functional coordination of the limbic circuit, enabling the segregation and integration of information flow across neuronal networks.
Hidden Markov Models Lead to Higher Resolution Maps of Mutation Signature Activity in Cancer
Authors: Huang Xiaoqing , Sason Itay , Wojtowicz Damian , Kim Yoo-Ah , Leiserson Mark D.M. , Przytycka Teresa M. , Sharan Roded
Published: August 2018

Knowing the activity of the mutational processes shaping a cancer genome may provide insight into tumorigenesis and personalized therapy. It is thus important to uncover the characteristicsignaturesof active mutational processes in patients from their patterns of single base substitutions. However, mutational processes do not act uniformly on the genome and are biased by factors such as the genome’s chromatin structure or replication origins. These factors may lead to statistical dependencies among neighboring mutations, calling for modeling approaches that can account for such dependencies to better estimate mutational process activities.

Here we develop the first sequence-dependent models for mutation signatures. We apply these models to characterize genomic and other factors that influence the activity of previously validated mutation signatures in breast cancer. We find that our tool, SigMa, can accurately assign genomic mutations to mutation signatures, yielding assignments that are of higher likelihood than those obtained with models that assume independence between signatures and align better with current biological knowledge. Our analysis resolves a controversy related to the dependency of APOBEC signatures on replication time and links Signatures 18 and 30 to oxidative damage.

Modeling the sequential dependencies of mutation signatures leads to improved estimates of mutation signature activity both at the tumor-level and within specific genomic regions, yielding higher resolution maps of mutation signature activity in cancer.
BAMM-SC: A Bayesian mixture model for clustering droplet-based single cell transcriptomic data from population studies
Authors: Sun Zhe , Chen Li , Xin Hongyi , Huang Qianhui , Cillo Anthony R , Tabib Tracy , Ding Ying , Kolls Jay K , Bruno Tullia C , Lafyatis Robert , Vignali Dario AA , Chen Kong , Hu Ming , Chen Wei
Published: August 2018

The recently developed droplet-based single cell transcriptome sequencing (scRNA-seq) technology makes it feasible to perform a population-scale scRNA-seq study, in which the transcriptome is measured for tens of thousands of single cells from multiple individuals. Despite the advances of many clustering methods, there are few tailored methods for population-scale scRNA-seq studies. Here, we have developed a BAyesiany Mixture Model for Single Cell sequencing (BAMM-SC) method to cluster scRNA-seq data from multiple individuals simultaneously. Specifically, BAMM-SC takes raw data as input and can account for data heterogeneity and batch effect among multiple individuals in a unified Bayesian hierarchical model framework. Results from extensive simulations and application of BAMM-SC to in-house scRNA-seq datasets using blood, lung and skin cells from humans or mice demonstrated that BAMM-SC outperformed existing clustering methods with improved clustering accuracy and reduced impact from batch effects. BAMM-SC has been implemented in a user-friendly R package with a detailed tutorial available on www.pitt.edu/~Cwec47/singlecell.html.
Positive selection in Europeans and East-Asians at the ABCA12 gene
Authors: Sirica Roberto , Buonaiuto Marianna , Petrella Valeria , Sticco Lucia , Tramontano Donatella , Antonini Dario , Missero Caterina , Guardiola Ombretta , Andolfi Gennaro , Kumar Heerman , Ayub Qasim , Xue Yali , Tyler-Smith Chris , Salvemini Marco , D’Angelo Giovanni , Colonna Vincenza
Published: August 2018

Natural selection acts on genetic variants by increasing the frequency of alleles responsible for a cellular function that is favorable in a certain environment. In a previous genome-wide scan for positive selection in contemporary humans, we identified a signal of positive selection in European and Asians at the genetic variant rs10180970. The variant is located in the second intron of the ABCA12 gene, which is implicated in the lipid barrier formation and down-regulated by UVB radiation. We studied the signal of selection in the genomic region surrounding rs10180970 in a larger dataset that includes DNA sequences from ancient samples. We also investigated the functional consequences of gene expression of the alleles of rs10180970 and another genetic variant in its proximity in healthy volunteers exposed to similar UV radiation.

We confirmed the selection signal and refine its location that extends over 35 kb and includes the first intron, the first two exons and the transcription starting site of ABCA12. We found no obvious effect of rs10180970 alleles on ABCA12 gene expression. We reconstructed the trajectory of the T allele over the last 80,000 years to discover that it was specific to H. sapiens and frequent among non-Africans already 45,000 years ago.
Estimation of narrowband amplitude and phase from electrophysiology signals for phase-amplitude coupling studies: a comparison of methods
Authors: Soto Juan L.P. , Prado Felipe V.D. , Combrisson Etienne , Jerbi Karim
Published: August 2018

Many functional connectivity studies based on electrophysiological measurements, such as electro- and magnetoencephalography (EEG/MEG), start their investigations by extracting a narrowband representation of brain activity time series, and then computing their envelope amplitudes and instantaneous phases, which serve as inputs to subsequent data processing. The two most popular approaches for obtaining these narrowband amplitudes and phases are: bandpass filtering followed by Hilbert transform (we call this the Hilbert approach); and convolution with wavelet kernels (the wavelet approach). In this work, we investigate how these two approaches perform in detecting the phenomenon of phase-amplitude coupling (PAC), whereby the amplitude of a high-frequency signal is driven by the phase of a low-frequency signal. The comparison of both approaches is carried out by means of simulated brain activity, from which we run receiver operating characteristic (ROC) analyses, and of experimental MEG data from a visuomotor coordination study. The ROC analyses show that both approaches have comparable accuracy, except in the presence of interfering signals with frequencies near the high-frequency band. As for the visuomotor data, the most noticeable impact of the choice of approach was observed when evaluating task-based changes in PAC between the delta (2-5 Hz) and the high-gamma (60-90 Hz) frequency bands, as we were able to identify widespread brain areas with statistically significant effects only with the Hilbert approach. These results provide preliminary evidence of the advantages of the Hilbert approach over the wavelet approach, at least in the context of PAC estimates.
Improving the classification of neuropsychiatric conditions using gene ontology terms as features
Authors: Quinn Thomas P. , Lee Samuel C. , Venkatesh Svetha , Nguyen Thin
Published: August 2018

Although neuropsychiatric disorders have a well-established genetic background, their specific molecular foundations remain elusive. This has prompted many investigators to design studies that identify explanatory biomarkers, and then use these biomarkers to predict clinical outcomes. One approach involves using machine learning algorithms to classify patients based on blood mRNA expression from high-throughput transcriptomic assays. However, these endeavours typically fail to achieve the high level of performance, stability, and generalizability required for clinical translation. Moreover, these classifiers can lack interpretability because informative genes do not necessarily have relevance to researchers. For this study, we hypothesized that annotation-based classifiers can improve classification performance, stability, generalizability, and interpretability. To this end, we evaluated the performance of four classification algorithms on six neuropsychiatric data sets using four annotation databases. Our results suggest that the Gene Ontology Biological Process database can transform gene expression into an annotation-based feature space that improves the performance and stability of blood-based classifiers for neuropsychiatric conditions. We also show how annotation features can improve the interpretability of classifiers: since annotation databases are often used to assign biological importance to genes, annotation-based classifiers are easy to interpret because the biological importance of the features are the features themselves. We found that using annotations as features improves the performance and stability of classifiers. We also noted that the top ranked annotations tend contain the top ranked genes, suggesting that the most predictive annotations are a superset of the most predictive genes. Based on this, and the fact that annotations are used routinely to assign biological importance to genetic data, we recommend transforming gene-level expression into annotation-level expression prior to the classification of neuropsychiatric conditions.