bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of Breast Size on Upper Torso Musculoskeletal Structure and Function: A Cross-Sectional Study
Authors: Coltman Celeste E. , Steele Julie R. , McGhee Deirdre E.
Published: February 2019

Background:

Research has shown that women with large and hypertrophic breast sizes report an increased prevalence and severity of musculoskeletal pain in the upper torso. Despite this evidence, factors contributing to the development of musculoskeletal pain among these women are poorly understood, and the threshold at which breast size becomes problematic in terms of musculoskeletal pain is currently unknown.

Methods:

Three hundred Australian women (aged 18 to 82 years) who volunteered as participants were divided into four breast size groups (small, breast volume <350 ml; medium, breast volume 350 to 700 ml; large, breast volume 701 to 1200 ml; and hypertrophic, breast volume >1200 ml). The thoracic flexion torque, thoracic kyphosis angle, total upper torso musculoskeletal pain score, and regional upper torso musculoskeletal pain scores derived for participants in the four groups were compared using an analysis of covariance design, controlling for age and body mass index.

Results:

Thoracic flexion torque significantly increased as breast size group increased. Women with hypertrophic breasts reported significantly higher total upper torso musculoskeletal pain scores compared with women who had small, medium, and large breasts, and this was significant for the upper back, shoulders, neck, and breasts. No significant difference was found in thoracic kyphosis angle among the four groups.

Conclusions:

Musculoskeletal pain became most pronounced in women with hypertrophic breasts who had the greatest breast volume and displayed the greatest thoracic flexion torque. Clinical and/or surgical treatment for symptomatic relief should aim to either counteract thoracic flexion torque or reduce breast volume.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Risk, I.
Eruption of Maxillary Posterior Permanent Molars following Early Conventional Le Fort III Advancement and Early Le Fort III Distraction Procedures Compared to Late Surgical Intervention
Authors: Gonchar Marina N. , Bekisz Jonathan M. , Grayson Barry H. , McCarthy Joseph G. , Shetye Pradip R.
Published: February 2019

Background:

Le Fort III advancement and/or distraction involve osteotomies and dysjunction in the region of the maxillary tuberosity in proximity to the maxillary posterior tooth buds. The purpose of this study was to determine the effect of early conventional Le Fort III advancement and/or distraction on development and eruption of the maxillary posterior permanent molars.

Methods:

A retrospective review of patients diagnosed with syndromic craniosynostosis, who underwent early Le Fort III or early midface distraction and late surgical intervention, was analyzed.

Results:

In the early conventional Le Fort III surgery group, 93 percent of maxillary second molars and 28 percent of maxillary first molars experienced a disturbance in eruption. In the early distraction group, 82 percent of maxillary second molars and 20 percent of maxillary first molars experienced a disturbance in eruption. In the control group, the late conventional Le Fort III and the late distraction groups, only 26 percent of maxillary second molars and none of maxillary first molars experienced a disturbance in eruption.

Conclusions:

A common disruption seen postoperatively in the early Le Fort III and distraction groups was displacement of the second molars. The majority of the displaced tooth buds were located in the maxillary sinus. Overall, the early Le Fort III surgery groups experienced more frequent disturbances for both first and second molars, with the common sequela of displacement in the maxillary sinus, leading to the question of whether presurgical planning in cases of early intervention to address midface retrusion should include extraction/enucleation of the second molar tooth buds.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, III.
Utility of Two Surgical Techniques Using a Lateral Intercostal Artery Perforator Flap after Breast-Conserving Surgery: A Single-Center Retrospective Study
Authors: Kim Jae Bong , Eom Jeung Ryeol , Lee Jeong Woo , Lee Jeeyeon , Park Ho Yong , Yang Jung Dug
Published: February 2019

Background:

Immediate partial breast reconstruction after breast-conserving surgery has become a new paradigm in treating breast cancer. Among the volume replacement techniques used for small to moderate-sized breasts, the perforator flap method has many advantages. The authors present anatomical studies and two surgical techniques using lateral intercostal artery perforator flaps.

Methods:

Data from 40 patients who underwent breast reconstruction using the lateral intercostal artery perforator flap between January of 2011 and June of 2016 were included. The authors conducted comparative analyses of the propeller flap and the turnover flap. They used three-dimensional computed tomography in lateral intercostal artery perforator flap anatomical studies, analyzing the distribution probability of the dominant perforator, the vertical distance from the axillary fold, and the horizontal distance from the anterior border of the latissimus dorsi.

Results:

The most dominant perforator used for lateral intercostal artery perforator flaps was the sixth lateral intercostal artery perforator (43.6 percent of cases), followed by the seventh lateral intercostal artery perforator (39.1 percent of cases); their mean distances from the latissimus dorsi and the axillary folds were determined and reported. Complications included three cases requiring additional treatment for fat necrosis (propeller method, two cases; turnover method, one case) and venous congestion in only two cases that used the propeller method. Cosmetic satisfaction was 90 percent or greater for both techniques, indicating that results were rated as either excellent or good.

Conclusion:

The authors believe that their study results can broaden the application of partial breast reconstruction by using the lateral intercostal artery perforator flap after breast-conserving surgery, with three-dimensional computed tomography for anatomical studies, and using one of the authors’ two described surgical techniques.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, III.
Correction of Lower Eyelid Retraction with En Glove Placement of Porcine Dermal Collagen Matrix Implant
Authors: Grumbine F. Lawson , Idowu Oulwatobi , Kersten Robert C. , Deparis Sarah W. , Vagefi M. Reza
Published: February 2019

The authors conducted a retrospective case series of patients undergoing a lateral tarsal strip procedure with “en glove” placement of an acellular porcine dermal collagen matrix for correction of mild to moderate lower eyelid retraction. A detailed description of this minimally invasive technique with retrospective analysis of outcomes is provided.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, IV.
Wide-Awake Surgical Management of Hand Fractures: Technical Pearls and Advanced Rehabilitation
Authors: Hyatt Brad T. , Rhee Peter Charles
Published: February 2019

Most unstable metacarpal and phalangeal fractures for which operative treatment is indicated can be reduced and stabilized with either open or closed techniques using local anesthetic with epinephrine instead of intravenous sedation or general anesthesia. With the patient wide-awake during surgery, the hand can be taken through active range of motion to assess fracture stability. In this article, the authors review the rationale and technique for wide-awake, local anesthesia, no tourniquet surgery in the treatment of phalangeal and metacarpal fractures and impart pearls to optimize the patient experience and illustrate common fixation techniques using percutaneous Kirschner wires. The intraoperative assessment of fracture stability permits an accelerated, protected–range-of-motion protocol that minimizes postoperative stiffness and facilitates expedient recovery.
Is Chest Computed Tomography Always Necessary Following Nephrectomy for Renal Cell Carcinoma? A Pilot Study in Single Tertiary Institution
Authors: Lee Hong Seon , Kang Won Jun , Cho Nam Hoon , Park Sung Yoon
Published: February 2019

Purpose

We evaluated patterns of thoracic recurrence from renal cell carcinoma (RCC) following nephrectomy as a pilot study.

Methods

Data of consecutive 39 patients who had recurrent RCC in the abdomen or thorax following curative nephrectomy were evaluated. Recurrence sites were analyzed with abdomen and chest computed tomography (CT), or positron emission tomography/CT. All patients had no metastasis before initial nephrectomy. Recurrence was classified into 3 types according to the site of initially detected recurrence: (a) abdomen-only type, (b) abdomen and thorax type, and (c) thorax-only type. Vertebral level of recurrence site in the thorax-only level was investigated. University of California Los Angeles–Integrated Staging System was utilized for risk stratification (eg, low, intermediate, and high-risk).

Results

Rate of intermediate or high risk was 89.7% (37/39). Rate of thoracic recurrence, regardless of concurrent abdominal recurrence, was 71.8% (28/39). Rate of thorax-only type was 53.8% (21/39). In thorax-only type, median vertebral level of recurrence site was T10 (range, T3–T12), and no patient with low risk had metastasis above the T10 level alone. In intermediate or high risk, 89.2% (33/37) had at least a recurrent lesion at the level of T7 or lower.

Conclusions

In low-risk patients, upper thoracic recurrence alone may be very rare after curative surgery. In majority of intermediate- or high-risk patients, initial recurrence may occur in the abdomen or lower thorax, which indicates abdomen CT covering T7 level may be an effective tool for postoperative follow-up in RCC.
Novel Hybrid Dextran-Gadolinium Nanoparticles as High-relaxivity T1 Magnetic Resonance Imaging Contrast Agent for Mapping the Sentinel Lymph Node
Authors: Lu Bolun , Wang Hao , Lu Qing , Tang Zhengya , Dou Hongjing , Dai Tingting , Li Shengli
Published: February 2019

Objectives

To assess the applicability of a novel hybrid dextran-gadolinium nanoparticles (NPs) as high-relaxivity T1 magnetic resonance imaging (MRI) contrast agent for mapping the sentinel lymph node (SLN).

Methods

Dextran-bis-acrylamide-polyacrylic acid (Dex-MBA-PAA) NPs were synthesized through a self-assembly assisted approach and complexed with multiple chelated gadolinium (Gd) (III) ions. After their characterization was validated, they were used to mapping SLNs by MRI in Wistar rats, and their biosafety was evaluated.

Results

Dextran-MBA-polyacrylic acid-Gd NPs have suitable particle size and much higher longitudinal relaxivity (r
1) than that of commonly used clinical MRI contrast agents (eg, gadopentetic acid dimeglumine salt injection). The in vivo T1-weighted MRI results revealed their effectiveness at mapping SLNs. And their biological safety was also verified.

Conclusions

Dextran-MBA-polyacrylic acid-Gd NPs were synthesized and validated by in vitro and in vivo experiments for their ability to visualize SLNs by MRI with accurate positioning and excellent biosafety, and they have great potential for clinical SLN mapping.
Comparison of Cone-Beam Computed Tomography and Multislice Computed Tomography in the Assessment of Extremity Fractures
Authors: Dubreuil Thibaut , Mouly Jérôme , Ltaief-Boudrigua Aïcha , Martinon Amanda , Tilhet-Coartet Stéphane , Tazarourte Karim , Pialat Jean-Baptiste
Published: February 2019

Objectives

The aims of this study were to evaluate the agreement between cone-beam computed tomography (CBCT) and multislice computed tomography for the characterization of extremity fractures and to compare image quality, radiation dose, and patient tolerance.

Methods

Thirty-six patients with suspected fracture affecting distal extremities or who required preoperative fracture assessment were enrolled prospectively. Each patient underwent CBCT and multislice computed tomography the same day. Both examinations were evaluated independently twice by 2 trained radiologists using the Müller AO classification for fracture characterization.

Results

Cohen κ coefficient for agreement between the imaging techniques was almost perfect for fracture characterization, κ = 0.94 [95% confidence interval, 0.91–0.98]. There was substantial to almost perfect agreement for secondary findings. Cone-beam computed tomography was well tolerated and significantly less irradiant and had better subjective image.

Conclusions

An excellent agreement between both imaging techniques was found. This confirms the ability of CBCT to assess fractures and its potential in the management of patients with distal limb trauma.
Circulatory Stasis or Thrombus in Left Atrial Appendage, An Easy Diagnostic Solution
Authors: Kantarci Mecit , Ogul Hayri , Sade Recep , Aksakal Enbiya , Colak Abdurrahim , Tanboga Ibrahim Halil
Published: February 2019

Objective

The purpose of this study was to assess the diagnostic performance of prone position cardiac multidetector computed tomography (MDCT) in the detection of left atrial appendage (LAA) thrombi and to make differentiate between thrombus and circulatory stasis using transesophageal echocardiography (TEE) as the criterion-standard imaging modality.

Methods

From December 2014 to April 2016, 53 consecutive patients were admitted to the hospital because of circulatory stasis or/and thrombus. All patients underwent prone-position MDCT and TEE. Prone-position MDCT and TEE sensitivity, specificity, positive predictive value, and negative predictive value were calculated.

Results

For the MDCT scan in the prone position, the sensitivity, specificity, positive predictive value, and negative predictive value results were 100%, 100%, 100%, and 100%, respectively.

Conclusions

Multidetector computed tomography scanning in the prone position differentiates circulatory stasis and LAA thrombus, is clinically useful for detecting and ruling out LAA thrombus, and may be an alternative to TEE as a diagnostic tool.
Imaging Spectrum of Double-Outlet Right Ventricle on Multislice Computed Tomography
Authors: Priya Sarv , Nagpal Prashant , Sharma Arun , Pandey Niraj N. , Jagia Priya
Published: February 2019

Double-outlet right ventricle is a complex congenital heart disease that encompasses various common and rare subtypes. Surgical management of these patients needs to be individualized owing to extremely variable morphology and hemodynamics. Imaging plays a crucial role in determination and characterization of outflow tract morphology. The assessment of ventricular septal defect routability with identification of associated anomalies has therapeutic implications in these patients. Multislice computed tomography with advanced 3-dimensional postprocessing techniques and dose-reduction strategies is invaluable in defining the anatomy and morphology of double-outlet right ventricle with simultaneous assessment of associated anomalies.
Computed Tomography Appearance of Uncorrected Congenital Heart Disease in Adults
Authors: Maldjian Pierre D. , Yen Li-Hsiang
Published: February 2019

The incidence of congenital heart disease (CHD) is about 4 to 10 per 1000 live births. While severe forms of CHD are usually diagnosed in infancy or childhood, milder and more survivable CHD may first manifest in the adult or may be discovered incidentally on imaging studies performed for other reasons. It is important to identify CHD in adults to implement appropriate treatment and prevent complications such as progression of pulmonary hypertension and development of heart failure. The goals of this article are to illustrate the appearance on computed tomography of various forms of uncorrected CHD in adults and describe the key features that characterize specific lesions.
Impact of the Myotomy Extent on Gastric Side on Surgical Outcome After Heller’s Cardiomotomy for Achalasia
Authors: El Nakeeb Ayman , Ezzat Helmy , Shehta Ahmed , El Gawad Mohamed A. , Abou El-Magd El-Sayed , El Sorogy Mohamed , Elrefei Mohamed , El-Geidi Ahmed A. , Gad El-Hak Nabil
Published: February 2019

Background:

Laparoscopic Heller cardiomyotomy (LHM) with Dor fundoplication represents the most commonly accepted surgical management for achalasia. The ideal extent of myotomy on the gastric side remains a matter of continuous debate. The aim of this study was to compare the impact of the extent of myotomy on the gastric side on the outcome of LHM.

Patients and Methods:

Patients with achalasia who underwent LHM included in the study. The patients were classified according to the length of the gastric myotomy into 3 groups (group I: <1.5 cm, group II: 1.5 to 2.5 cm, and group III: >2.5 cm).

Results:

In total, 212 patients (94 males and 118 females) with achalasia treated by LHM and Dor fundoplication included in the study. No statistically significant differences were found among the 3 groups as regards preoperative data, intraoperative mucosal perforation, operative time, blood loss, and hospital stay. The incidence of persistent dysphagia was significantly higher in the group I. Postoperative GERD symptoms were significantly higher in group III (23.3%, P<0.0001). Recurrent achalasia was significantly higher in group I with 11 patients (15.9%), 8 patients in group II (7.1%), and nil in group III (P<0.02).

Conclusions:

Longer myotomy on the gastric side (>2.5 cm) ensures complete division of the LES with better outcomes in term of resolution of dysphagia but may be associated with higher postoperative GERD. Therefore, a myotomy length of 1.5 to 2.5 cm on the gastric side provides a balance between relieve of dysphagia and development of postoperative GERD.
Regulation of endothelial cell permeability by platelet-derived extracellular vesicles
Authors: Miyazawa Byron , Trivedi Alpa , Togarrati Padma Priya , Potter Daniel , Baimukanova Gyulnar , Vivona Lindsay , Lin Maximillian , Lopez Ernesto , Callcut Rachael , Srivastava Amit K. , Kornblith Lucy Z. , Fields Alexander T. , Schreiber Martin A. , Wade Charles E. , Holcomb John B. , Pati Shibani
Published: February 2019

BACKGROUND

Platelet (Plt)-derived extracellular vesicles (Plt-EVs) have hemostatic properties similar to Plts. In addition to hemostasis, Plts also function to stabilize the vasculature and maintain endothelial cell (EC) barrier integrity. We hypothesized that Plt-EVs would inhibit vascular EC permeability, similar to fresh Plts. To investigate this hypothesis, we used in vitro and in vivo models of vascular endothelial compromise and bleeding.

METHODS

In the vitro model, Plt-EVs were isolated by ultracentrifugation and characterized for Plt markers and particle size distribution. Effects of Plts and Plt-EVs on endothelial barrier function were assessed by transendothelial electrical resistance measurements and histological analysis of endothelial junction proteins. Hemostatic potential of Plt-EVs and Plts was assessed by multiple electrode Plt aggregometry. Using an in vivo model, the effects of Plts and Plt-EVs on vascular permeability and bleeding were assessed in non-obese diabetic-severe combined immunodeficient (NOD-SCID) mice by an established Miles assay of vascular permeability and a tail snip bleeding assay.

RESULTS

In the in vitro model, Plt-EVs displayed exosomal size distribution and expressed Plt-specific surface markers. Platelets and Plt-EVs decreased EC permeability and restored EC junctions after thrombin challenge. Multiplate aggregometry revealed that Plt-EVs enhanced thrombin receptor–activating peptide-mediated aggregation of whole blood, whereas Plts enhanced thrombin receptor–activating peptide–, arachidonic acid–, collagen-, and adenosine diphosphate–mediated aggregation. In the in vivo model, Plt-EVs are equivalent to Plts in attenuating vascular endothelial growth factor (VEGF)-A–induced vascular permeability and uncontrolled blood loss in a tail snip hemorrhage model.

CONCLUSION

Our study is the first to report that Plt-EVs might provide a feasible product for transfusion in trauma patients to attenuate bleeding, inhibit vascular permeability, and mitigate the endotheliopathy of trauma.
Phase I/II Trial of Liver–derived Mesenchymal Stem Cells in Pediatric Liver–based Metabolic Disorders: A Prospective, Open Label, Multicenter, Partially Randomized, Safety Study of One Cycle of Heterologous Human Adult Liver–derived Progenitor Cells (HepaStem) in Urea Cycle Disorders and Crigler-Najjar Syndrome Patients
Authors: Smets Françoise , Dobbelaere Dries , McKiernan Patrick , Dionisi-Vici Carlo , Broué Pierre , Jacquemin Emmanuel , Lopes Ana Isabel , Gonçalves Isabel , Mandel Hanna , Pawlowska Joanna , Kamińska Diana , Shteyer Eyal , Torre Giuliano , Shapiro Riki , Eyskens François , Clapuyt Philippe , Gissen Paul , Pariente Danièle , Grunewald Stephanie , Yudkoff Marc , Binda Maria Mercedes , Najimi Mustapha , Belmonte Nathalie , de Vos Beatrice , Thonnard Joelle , Sokal Etienne
Published: February 2019

Background.

Regenerative medicine using stem cell technology is an emerging field that is currently tested for inborn and acquired liver diseases.

Objective.

This phase I/II prospective, open label, multicenter, randomized trial aimed primarily at evaluating the safety of Heterologous Human Adult Liver–derived Progenitor Cells (HepaStem) in pediatric patients with urea cycle disorders (UCDs) or Crigler-Najjar (CN) syndrome 6 months posttransplantation. The secondary objective included the assessment of safety up to 12 months postinfusion and of preliminary efficacy.

Methods.

Fourteen patients with UCDs and 6 with CN syndrome were divided into 3 cohorts by body weight and intraportally infused with 3 doses of HepaStem. Clinical status, portal vein hemodynamics, morphology of the liver, de novo detection of circulating anti–human leukocyte antigen antibodies, and clinically significant adverse events (AEs) and serious adverse events to infusion were evaluated by using an intent-to-treat analysis.

Results.

The overall safety of HepaStem was confirmed. For the entire study period, patient-month incidence rate was 1.76 for the AEs and 0.21 for the serious adverse events, of which 38% occurred within 1 month postinfusion. There was a trend of higher events in UCD as compared with CN patients. Segmental left portal vein thrombosis occurred in 1 patient and intraluminal local transient thrombus in a second patient. The other AEs were in line with expectations for catheter placement, cell infusion, concomitant medications, age, and underlying diseases.

Conclusions.

This study led to European clinical trial authorization for a phase II study in a homogeneous patient cohort, with repeated infusions and intermediate doses.
Coronary Artery Disease and Coronary Artery Bypass Grafting at the Time of Lung Transplantation Do Not Impact Overall Survival
Authors: Halloran Kieran , Hirji Alim , Li David , Jackson Kathy , Kapasi Ali , Meyer Steve , Mullen John , Lien Dale , Weinkauf Justin
Published: February 2019

Background.

Coronary artery disease (CAD) is common in lung transplant candidates and may require revascularization before or at the time of their transplant. We reviewed the survival of lung transplant recipients with CAD requiring surgical intervention (CAD-coronary artery bypass grafting [CABG]) and those who did not (CAD-NoCABG) at the time of transplant, compared to a cohort with no CAD (NoCAD).

Methods.

We conducted a retrospective cohort study of adult patients transplanted in our program between 2004 and 2013. Our primary outcome was the association between 3-way CAD status (CAD-CABG, CAD-NoCABG, NoCAD) and overall retransplant-free survival via proportional hazards modeling, adjusting for age, gender, and transplant indication. Secondary endpoints included 1-year survival, survival by Kaplan-Meier analysis, duration of ventilation, intensive care unit stay, and hospitalization.

Results.

A total of 333 patients underwent transplant during the study timeframe. A total of 24 (7%) had CAD requiring CABG, 82 (25%) had CAD not requiring CABG, and the remaining 227 had no CAD. The 3-way CAD status was not associated with overall retransplant-free survival after adjustment for age, gender, and transplant indication. Duration of mechanical ventilation, intensive care unit stay and hospitalization were longer in both CAD groups compared with the NoCAD group.

Conclusions.

CAD status does not impact overall retransplant-free survival, despite greater perioperative complexity. Prospective studies comparing treatment strategies in these patient groups are warranted.
Safety of Everolimus With Reduced Calcineurin Inhibitor Exposure in De Novo Kidney Transplants: An Analysis From the Randomized TRANSFORM Study
Authors: Tedesco-Silva Helio , Pascual Julio , Viklicky Ondrej , Basic-Jukic Nikolina , Cassuto Elisabeth , Kim Dean Y. , Cruzado Josep M. , Sommerer Claudia , Adel Bakr Mohamed , Garcia Valter D. , Uyen Huynh-Do , Russ Graeme , Soo Kim Myoung , Kuypers Dirk , Buchler Matthias , Citterio Franco , Hernandez Gutierrez Maria Pilar , Bernhardt Peter , Chadban Steve
Published: February 2019

Background.

The safety profiles of standard therapy versus everolimus with reduced-exposure calcineurin inhibitor (CNI) therapy using contemporary protocols in de novo kidney transplant recipients have not been compared in detail.

Methods.

TRANSFORM was a randomized, international trial in which de novo kidney transplant patients were randomized to everolimus with reduced-exposure CNI (N = 1014) or mycophenolic acid (MPA) with standard-exposure CNI (N = 1012), both with induction and corticosteroids.

Results.

Within the safety population (everolimus 1014, MPA 1012), adverse events with a suspected relation to study drug occurred in 62.9% versus 59.2% of patients given everolimus or MPA, respectively (P = 0.085). Hyperlipidemia, interstitial lung disease, peripheral edema, proteinuria, stomatitis/mouth ulceration, thrombocytopenia, and wound healing complications were more frequent with everolimus, whereas diarrhea, nausea, vomiting, leukopenia, tremor, and insomnia were more frequent in the MPA group. The incidence of viral infections (17.2% versus 29.2%; P < 0.001), cytomegalovirus (CMV) infections (8.1% versus 20.1%; P < 0.001), CMV syndrome (13.6% versus 23.0%, P = 0.044), and BK virus (BKV) infections (4.3% versus 8.0%, P < 0.001) were less frequent with everolimus. CMV infection was less common with everolimus versus MPA after adjusting for prophylaxis therapy in the D+/R− subgroup (P < 0.001). Study drug was discontinued more frequently due to rejection or impaired healing with everolimus, and more often due to BKV infection or BKV nephropathy with MPA.

Conclusions.

De novo everolimus with reduced-exposure CNI yielded a comparable incidence, though a distinctly different pattern, of adverse events versus current standard of care. Both regimens are safe and effective, yet their distinct profiles may enable tailoring for individual kidney transplant recipients.
Geographic Disparity in Deceased Donor Liver Transplant Rates Following Share 35
Authors: Bowring Mary G. , Zhou Sheng , Chow Eric K.H. , Massie Allan B. , Segev Dorry L. , Gentry Sommer E.
Published: February 2019

Background.

The Organ Procurement and Transplantation Network implemented Share 35 on June 18, 2013, to broaden deceased donor liver sharing within regional boundaries. We investigated whether increased sharing under Share 35 impacted geographic disparity in deceased donor liver transplantation (DDLT) across donation service areas (DSAs).

Methods.

Using Scientific Registry of Transplant Recipients June 2009 to June 2017, we identified 86 083 adult liver transplant candidates and retrospectively estimated Model for End-Stage Liver Disease (MELD)-adjusted DDLT rates using nested multilevel Poisson regression with random intercepts for DSA and transplant program. From the variance in DDLT rates across 49 DSAs and 102 programs, we derived the DSA-level median incidence rate ratio (MIRR) of DDLT rates. MIRR is a robust metric of heterogeneity across each hierarchical level; larger MIRR indicates greater disparity.

Results.

MIRR was 2.18 pre-Share 35 and 2.16 post-Share 35. Thus, 2 candidates with the same MELD in 2 different DSAs were expected to have a 2.2-fold difference in DDLT rate driven by geography alone. After accounting for program-level heterogeneity, MIRR was attenuated to 2.10 pre-Share 35 and 1.96 post-Share 35. For candidates with MELD 15–34, MIRR decreased from 2.51 pre- to 2.27 post-Share 35, and for candidates with MELD 35–40, MIRR increased from 1.46 pre- to 1.51 post-Share 35, independent of program-level heterogeneity in DDLT. DSA-level heterogeneity in DDLT rates was greater than program-level heterogeneity pre- and post-Share 35.

Conclusions.

Geographic disparity substantially impacted DDLT rates before and after Share 35, independent of program-level heterogeneity and particularly for candidates with MELD 35–40. Despite broader sharing, geography remains a major determinant of access to DDLT.
Transplant Suitability of Rejected Human Donor Lungs With Prolonged Cold Ischemia Time in Low-Flow Acellular and High-Flow Cellular Ex Vivo Lung Perfusion Systems
Authors: Okamoto Toshihiro , Wheeler David , Farver Carol F. , McCurry Kenneth R.
Published: February 2019

Background.

Ex vivo lung perfusion (EVLP) has the potential to increase the number of donor lungs available for lung transplantation (LTx). While the current maximum cold ischemia time (CIT) for donor lungs in clinical LTx is around 8 hours, there are no data regarding the potential use of rejected donor lungs with CIT >8 hours before EVLP. The purpose of this study was to investigate the transplant suitability of lungs with a prolonged CIT in 2 EVLP systems.

Methods.

Following prolonged CIT of 13.8 hours (range 9.0–19.5 h), 16 rejected human donor lungs were randomly divided and perfused using either low-flow acellular or high-flow cellular EVLP systems (n = 8, each). Transplant suitability was evaluated according to the standard criteria of each EVLP system.

Results.

The high-flow cellular group was associated with a significantly lower transplant suitability (0% versus 37%, P = 0.027), significantly lower wet-to-dry ratio change (−0.71 ± 0.62 versus 0.43 ± 1.01, P = 0.035), and lower pathological score (1.62 ± 0.61 versus 3.00 ± 0.61, P = 0.163) than the low-flow acellular group. In both systems, inflammatory cytokines on perfusate (tumor necrosis factor-α, interleukin [IL]-1ß, IL-6, IL-8, and IL-10) increased in a time-dependent manner and were significantly higher than those of controls with CIT <8 hours (P < 0.05).

Conclusions.

The potential for reconditioning lungs with a CIT >8 hours is diminished compared with that for lungs having a shorter CIT due to severe ischemia reperfusion injury.
Australian Nurses' Knowledge of Pressure Injury Prevention and Management
Authors: Fulbrook Paul , Lawrence Petra , Miles Sandra
Published: February 2019

PURPOSE:

The aim of this study was to assess nurses' knowledge of pressure injuries in order to gather benchmark data, identify knowledge gaps, and based on results, implement educational strategies to improve practice.

DESIGN:

Cross-sectional survey.

SUBJECTS AND SETTING:

The study setting was a large Australian tertiary general hospital employing approximately 2500 nurses in both full-time and part-time roles. A proportional sample (25%) stratified by experience, preparation, and facility-generated categories (nursing grade) was generated. The sample included nursing students and nursing assistants. Three hundred six participants completing the survey.

INSTRUMENT:

The Pieper-Zulkowski Pressure Ulcer Knowledge Test (PZPUKT) version 2, comprising 72 statements, with 3 subscales (prevention/risk, staging, and wound description) was used to measure pressure injury knowledge. Item responses are “True,” “False,” and “Don't know.” For the purpose of analyses, correct responses were scored 1, and incorrect or “don't know” responses were scored 0. Generally accepted ranges of scoring for the original PZPUKT specify less than 70% as unsatisfactory, 70% to 79.9% as satisfactory, 80% to 89.9% as good, and 90% and greater as very good knowledge of pressure injury prevention.

METHODS:

The survey was advertised throughout the hospital by strategically placed posters, computer screen savers within the hospital, and e-mails. Respondents completed paper-based questionnaires and data were manually entered online. Data were collected between September 2015 and October 2016. Descriptive and nonparametric inferential statistical tests (Mann-WhitneyU, Kruskal-WallisH) were used to analyze within sample differences in scores.

RESULTS:

The overall mean knowledge score was 65%; approximately two-thirds of the sample (68%) scored 60% and greater, reflecting an unsatisfactory knowledge level of pressure injury prevention according to the original PZPUKT scores. The lowest mean scores were found in the “wound description” subscale. Participants who sought pressure injury information via the Internet or had read pressure injury guidelines scored significantly higher than those who did not (P= .001 andP< .001, respectively). Seventeen items were answered incorrectly by over half of participants, identifying important knowledge deficits, particularly within the wound description subscale.

CONCLUSIONS:

When compared with results from studies using the PZPUKT, we contend that a cutoff score of 60% and greater (instead of ≥70%) should be used to indicate an overall satisfactory score. Our results identified deficits in pressure injury knowledge related to seating support and seated individuals and wound dressings as areas where nurses would benefit from focused education strategies.
Molecular architecture of a membrane-spanning hormone acyltransferase required for metabolic regulation
Authors: Campaña Maria B. , Irudayanathan Flaviyan Jerome , Davis Tasha R. , McGovern-Gooch Kayleigh R. , Loftus Rosemary , Ashkar Mohammad , Escoffery Najae , Navarro Melissa , Sieburg Michelle A. , Nangia Shikha , Hougland James L.
Published: February 2019

Integral membrane proteins represent a large and essential portion of the proteome that often prove challenging for structural studies. We demonstrate a synergistic approach to structurally model topologically complex integral membrane proteins by combining co-evolutionary constraints and computational modeling with biochemical validation. We report the first structural model of a eukaryotic membrane-bound O-acyltransferase (MBOAT), ghrelin O-acyltransferase (GOAT), which modifies the metabolism-regulating hormone ghrelin. Our structure suggests an unanticipated strategy for trans-membrane protein acylation, with catalysis occurring in an internal channel as GOAT acts as an “enzyme inside a pore”. Our structure opens the door to structure-guided inhibitor design targeting GOAT and other MBOAT family members while validating the power of our approach to generate predictive structural models for other experimentally challenging integral membrane proteins.
Population responses of naïve roe deer to the recolonization of the French Vercors by wolves
Authors: Randon M , Bonenfant C , Michallet J , Chevrier T , Toïgo C , Gaillard J-M , Valeix M
Published: February 2019

In a context of rapidly changing carnivore populations worldwide, it is crucial to understand the consequences of these changes for prey populations. The recolonization by wolves of the French Vercors mountain range and the long-term monitoring (2001-2017) of roe deer populations provided us a unique opportunity to assess both lethal and non-lethal effects of wolves on these populations. We compared roe deer population abundance and growth, fawn body mass, and browsing intensity in two contrasted areas: a central area (core of a wolf pack territory characterized by an intense use by wolves) and a peripheral area (used more occasionally). Both populations of roe deer strongly dropped after an extremely severe winter but the population of the central area facing with wolves was slower to recover (due to a much lower growth rate the following year) and remained at lower abundance levels for 5 years. Fawn body mass was lower in the central area during that period and was not influenced by weather conditions or population abundance. The browsing index in the forests in presence of wolves decreased for a longer period, suggesting that possible habitat shifts have occurred. Altogether, the effects of wolves on the roe deer population in the central area occurred mainly during a 5-year period following the establishment of wolves, with effects at the population level in the first years only through the interplay between wolf predation (before wolves started preying on red deer), harsh winter conditions and naïveté of prey to this recolonizing predator.
Latent Mycobacterium tuberculosis infection provides protection for the host by changing the activation state of the innate immune system
Authors: Nemeth Johannes , Olson Gregory S. , Rothchild Alissa , Jahn Ana , Mai Dat , Duffy Fergal , Delahaye Jared , Srivatsan Sanjay , Plumlee Courtney , Urdahl Kevin , Gold Elizabeth , Diercks Alan , Aderem Alan
Published: February 2019

An efficacious vaccine against adult tuberculosis (TB) remains elusive. Progress is hampered by an incomplete understanding of the immune mechanisms that protect against infection with Mycobacterium tuberculosis (Mtb), the causative agent of TB1. Over 90% of people who become infected with Mtb mount an immune response that contains the bacteria indefinitely, leading to a state known as “latent TB infection” (LTBI)2. A significant body of epidemiologic evidence indicates that LTBI protects against active TB after re-exposure, offering an intriguing avenue to identifying protective mechanisms3, 4. We show that in a mouse model, LTBI is highly protective against infection with Mtb for up to 100 days following aerosol challenge. LTBI mice are also protected against heterologous bacterial challenge (Listeria monocytogenes) and disseminated melanoma suggesting that protection is in part mediated by alterations in the activation state of the innate immune system. Protection is associated with elevated activation of alveolar macrophages (AM), the first cells that respond to inhaled Mtb, and accelerated recruitment of Mtb-specific T cells to the lung parenchyma upon aerosol challenge. Systems approaches, including transcriptome analysis of both naïve and infected AMs, as well as ex vivo functional assays, demonstrate that LTBI reconfigures the response of tissue resident AMs.. Furthermore, we demonstrate that both LTBI mice and latently infected humans show similar alterations in the relative proportions of circulating innate immune cells, suggesting that the same cellular changes observed in the LTBI mouse model are also occurring in humans. Therefore, we argue that under certain circumstances, LTBI could be beneficial to the host by providing protection against subsequent Mtb exposure.
De novo compartment deconvolution and weight estimation of tumor samples (DECODER)
Authors: Peng Xianlu Laura , Moffitt Richard A , Torphy Robert J , Volmar Keith E , Yeh Jen Jen
Published: February 2019

Tumors are mixtures of different compartments. While global gene expression analysis profiles the average expression of all compartments in a sample, identifying the specific contribution of each compartment remains a challenge. With the increasing recognition of the importance of non-neoplastic components, the ability to breakdown the gene expression contribution of each is critical. To this end, we developed DECODER, an integrated framework which performs de novo deconvolution, and compartment weight estimation for a single sample. We use DECODER to deconvolve 33 TCGA tumor RNA-seq datasets and show that it may be applied to other data types including ATAC-seq. We demonstrate that it can be utilized to reproducibly estimate cellular compartment weights in pancreatic cancer that are clinically meaningful. Application of DECODER across cancer types advances the capability of identifying cellular compartments in an unknown sample and may have implications for identifying the tumor of origin for cancers of unknown primary.
A new pathway of pre-tRNA surveillance in yeast
Authors: Payea Matthew J. , De Zoysa Thareendra C. , Phizicky Eric M.
Published: February 2019

During tRNA maturation in yeast, aberrant pre-tRNAs are targeted for 3’-5’ degradation by the nuclear surveillance pathway, and mature tRNAs are targeted for 5’-3’ degradation by the rapid tRNA decay (RTD) pathway, due to lack of certain body modifications or to destabilizing mutations. Here we show that the RTD pathway also targets pre-tRNAs through an unknown, but distinct, mechanism that occurs after nuclear export. Anticodon stem RTD variants of both tRNATyrand tRNASer(CGA)are substrates for pre-tRNA RTD, triggered by the accumulation of end-matured unspliced pre-tRNA due to altered secondary structure of the region comprising the anticodon stem-loop and the intron. Furthermore, increased nuclear availability of a pre-tRNA RTD substrate can provoke decay by nuclear surveillance. We interpret these results in terms of a model of opportunistic tRNA decay, wherein tRNAs are degraded due to a combination of structural instability and increased availability to decay pathways.
Molecular Dynamics Simulations of Glycosaminoglycan Oligosaccharide Using Newer Force Fields
Authors: Nagarajan Balaji , Sankaranarayanan Nehru Viji , Desai Umesh R.
Published: February 2019

Heparin/heparan sulfate (H/HS) are ubiquitous biopolymers that interact with many proteins to induce myriad biological functions. It is critical to understand conformational properties of H/HS in solution so as to identify their preferred protein targets. Unfortunately, the massive heterogeneity of H/HS precludes the use of solution-based experimental techniques for the thousands of sequences that occur in nature. Computational simulations offer an attractive alternative and several all-atom force fields have been developed to understand their conformational properties. Recently, CHARMM36 carrying parameters forN-sulfamate was developed. This work compares molecular dynamics simulations of a hexasaccharide (HS06) using two all-atom force fields – CHARMM36 and GLYCAM06. We also introduce two new straightforward parameters, including end-to-end distance and minimum volume enclosing ellipsoid, to understand the conformational behavior of HS06. In addition, we analyzed inter- and intra-molecular hydrogen bonds and intermediate water bridges formed for HS06 using both force fields. Overall, CHARMM36 and GLYCAM06 gave comparable results, despite few, small differences. The MD simulations show that HS06 samples a range of conformations in solution with more than one nearly equivalent global minima, which contrasts with the assumed single conformation conclusion derived on the basis of 1HPN structure. A key reason for the stability of multiple low energy conformations was the contribution of intermediate water bridges, which is usually not evaluated in most MD studies of H/HS.
Analysis of movement recursions to detect reproductive events and estimate their fate in central place foragers
Authors: Picardi Simona , Smith Brian J. , Boone Matthew E. , Frederick Peter C. , Cecere Jacopo G. , Rubolini Diego , Serra Lorenzo , Pirrello Simone , Borkhataria Rena R. , Basille Mathieu
Published: February 2019

Recursive movement patterns have been used to detect behavioral structure within individual movement trajectories in the context of foraging ecology, home-ranging behavior, and predator avoidance. Some animals exhibit movement recursions to locations that are tied to reproductive functions, including nests and dens; while existing literature recognizes that, no method is currently available to explicitly target different types of revisited locations. Moreover, the temporal persistence of recursive movements to a breeding location can carry information regarding the fate of breeding attempts, but it has never been used as a metric to quantify recursive movement patterns. Here, we introduce a method to locate breeding attempts and estimate their fate from GPS-tracking data of central place foragers. We tested the performance of our method in three bird species differing in breeding ecology (wood stork (Mycteria americana), lesser kestrel (Falco naumanni), Mediterranean gull (Ichthyaetus melanocephalus)) and implemented it in the R package ‘nestR’. We identified breeding sites based on the analysis of recursive movements within individual tracks. Using trajectories with known breeding attempts, we estimated a set of species-specific criteria for the identification of nest sites, which we further validated using non-reproductive individuals as controls. We then estimated individual nest survival as a binary measure of reproductive fate (success, corresponding to fledging of at least one chick, or failure) from nest-site revisitation histories during breeding attempts, using a Bayesian hierarchical modeling approach that accounted for temporally variable revisitation patterns, probability of visit detection, and missing data. Across the three species, positive predictive value of the nest-site detection algorithm varied between 87-100% and sensitivity between 88-92%, and we correctly estimated the fate of 86-100% breeding attempts. By providing a method to formally distinguish among revisited locations that serve different ecological functions and introducing a probabilistic framework to quantify temporal persistence of movement recursions, we demonstrated how the analysis of recursive movement patterns can be applied to estimate reproduction in central place foragers. Beyond avian species, the principles of our method can be applied to other central place foraging breeders such as denning mammals. Our method estimates a component of individual fitness from movement data and will help bridge the gap between movement behavior, environmental factors, and their fitness consequences.
CD29 marks superior cytotoxic human T cells
Authors: Nicolet Benoît P. , Guislain Aurélie , van Alphen Floris P.J. , Gomez-Eerland Raquel , Schumacher Ton N. M. , den Biggelaar Maartje van , Wolkers Monika C.
Published: February 2019

Cytotoxic CD8+T cells can effectively kill target cells by producing cytokines, chemokines and granzymes. Expression of these effector molecules is however highly divergent, and tools that identify and pre-select potent killer cells are lacking. Human CD8+T cells can be divided into IFN-γ and IL-2 producing cells. Unbiased RNA-sequencing and proteomics analysis on cytokine-producing fixed cells revealed that IL-2+T cells produce helper cytokines, and that IFN-γ+T cells produce cytotoxic molecules. IFN-γ+T cells could be identified with the surface marker CD29 already prior to stimulation. CD29 also marked T cells with cytotoxic gene expression from different tissues in single-cell RNA-sequencing data. Notably, the cytotoxic features of CD29+T cells were maintained during cell culture, suggesting a stable phenotype. Pre-selecting CD29-expressing MART1 TCR-engineered T cells potentiated the killing of target cells. We therefore propose that selecting for CD29+T cells could boost the anti-tumoral activity of T cell therapeutics.