bluuebunny/crossref_metadata_2025 huggingface dataset:
Decreased Expression of Cystathionine β-Synthase Exacerbates Intestinal Barrier Injury in Ulcerative Colitis
Authors: Chen Shanwen , Zuo Shuai , Zhu Jing , Yue Taohua , Bu Dingfang , Wang Xin , Wang Pengyuan , Pan Yisheng , Liu Yucun
Published: January 2019

Background and Aims

Endogenous H2S regulates multiple physiological and pathological processes in colon epithelial tissues. The current study investigated the role of cystathionine β-synthase [CBS], a major producer of H2S in colon epithelial cells, in the pathogenesis of ulcerative colitis [UC]-related intestinal barrier injury. The expression and DNA methylation level of CBS were investigated in inflamed and non-inflamed colon tissues collected from UC patients, and the effect of decreased CBS levels on Caco-2 monolayer barrier injury and altered status of tight junctions elicited by tumour necrosis factor/interferon [TNF/IFN] was determined.

Methods

The expression of CBS and the methylation level of the CBS promoter were assessed in non-inflamed and inflamed colon epithelial tissue samples collected from UC patients. Barrier function, status of tight junction proteins and activation of the NF-κB p65-mediated MLCK-P-MLC signalling pathway were further investigated in Caco-2 monolayers.

Results

Decreased expression of CBS and elevated methylation levels of the CBS promoter were observed in inflamed sites compared with in non-inflamed sites in the colon epithelial samples from UC patients. In Caco-2 monolayers, decreased expression of CBS exacerbated TNF/IFN-induced barrier injury and altered localization of tight junction proteins. Decreased expression of CBS predisposed Caco-2 monolayers to injury elicited by TNF/IFN via augmentation of the NF-κB p65-mediated MLCK-P-MLC signalling pathway.

Conclusions

Decreased expression of CBS propagates the pathogenesis of UC by exacerbating inflammation-induced intestinal barrier injury. Elevated methylation of the CBS promoter might be one of the mechanisms underlying the decreased expression of CBS in inflamed sites of colon epithelial tissues from UC patients.
Prospective Study of Psychological Morbidity and Illness Perceptions in Young People With Inflammatory Bowel Disease
Authors: Brooks Alenka J , Norman Paul , Peach Emily J , Ryder Anna , Scott Alexander J , Narula Priya , Corfe Bernard M , Lobo Alan J , Rowse Georgina
Published: January 2019

Background and Aims

Psychological morbidity is increased in young people with inflammatory bowel disease [IBD]. Illness perceptions may be an important factor. This study aimed to describe the prevalence and severity of psychological morbidity and to examine relationships between baseline illness perceptions and anxiety, depression, and health-related quality of life [HRQoL], at baseline and 12 months later, in 16–21 year olds with IBD.

Methods

IBD patients [n = 121] completed measures of anxiety, depression, HRQoL, and illness perceptions [IPQ-R] at baseline and follow-up [n = 100, 83%].

Results

Among the 121 patients at baseline [median age 19.3 years, 40% female, 62% Crohn’s disease, 73% in clinical remission], 55% reported elevated symptoms of anxiety/depression and 83% reported low HRQoL. Negative illness perceptions at baseline were significantly correlated with greater anxiety, depression, and lower HRQoL at baseline and follow-up. In regression analysis at baseline, the IPQ-R domain of greater perception of a cyclical nature of IBD was an independent predictor of anxiety, and a greater perceived emotional impact of IBD was an independent predictor of anxiety, depression, and HRQoL. Female gender and clinical relapse were also independent predictors of lower HRQoL. After controlling for baseline measures, clinical risk factors and illness perceptions did not explain additional variance in psychological morbidity at follow-up.

Conclusions

A high prevalence of psychological morbidity, stable over 1 year, was demonstrated in young people with IBD. Having negative illness perceptions, being female, and having active disease predicted those at greatest risk of psychological morbidity. Illness perceptions may be an appropriate target for psychological interventions.
Multisectoral Collaborations to Increase the Use of Recommended Cancer Screening and Other Clinical Preventive Services by Older Adults
Authors: Kietzman Kathryn G , Toy Peggy , Bravo Rosana L , Duru O Kenrik , Wallace Steven P
Published: January 2019

The Healthy Aging Partnerships in Prevention Initiative (HAPPI) is a multisectoral collaboration that aims to increase use of recommended cancer screening and other clinical preventive services (CPS) among underserved African American and Latino adults aged 50 and older in South Los Angeles. HAPPI uses the principles of the evidence-based model Sickness Prevention Achieved through Regional Collaboration to increase capacity for the delivery of breast, cervical, and colorectal cancer screening, as well as influenza and pneumococcal immunizations, and cholesterol screening. This article describes HAPPI’s collaborative efforts to enhance local capacity by training personnel from community health centers (CHCs) and community-based organizations (CBOs), implementing a small grants program, and forming a community advisory council. HAPPI demonstrates that existing resources in the region can be successfully linked and leveraged to increase awareness and receipt of CPS. Five CHCs expanded quality improvement efforts and eight CBOs reached 2,730 older African Americans and Latinos through locally tailored educational programs that encouraged community–clinic linkages. A community council assumed leadership roles to ensure HAPPI sustainability. The lessons learned from these collective efforts hold promise for increasing awareness and fostering the use of CPS by older adults in underserved communities.
‘Leaky’ Bodies, Connectivity and Embodied Transitional Justice
Authors: Clark Janine Natalya
Published: January 2019

Abstract∞

Within the ever-growing field of transitional justice, it is striking that little attention has been given to bodies, except in the sense of what has been done to them. Seeking to address this gap by focusing on what bodies can do, this interdisciplinary article argues that bodies represent important sites of connectivity that can bring together communities fractured by war and armed conflict. In developing this thesis, it emphasizes how the leakiness of bodies – which has traditionally been viewed in negative terms – can help to foster a positive awareness of corporeal connectivity. Distinguishing between what it terms grounded and meta-functional connectivity, it calls for embodied ways of doing transitional justice that operationalize both types of connectivity. While the article is primarily a theoretical and conceptual piece, its empirical threads draw from the author’s recent fieldwork with victims–survivors of conflict-related sexual violence in Bosnia and Herzegovina, Colombia and Uganda.
Ascending Chain Condition for F-Pure Thresholds with Fixed Embedding Dimension
Authors: Sato Kenta
Published: January 2019

In this paper, we prove that the set of all $F$-pure thresholds of ideals with fixed embedding dimension satisfies the ascending chain condition. As a corollary, given an integer $d$, we verify the ascending chain condition for the set of all $F$-pure thresholds on all $d$-dimensional normal locally complete intersection varieties. In the process of proving these results, we also show the rationality of $F$-pure thresholds of ideals on non-strongly $F$-regular pairs.
Loss of TET proteins in regulatory T cells promotes abnormal proliferation, Foxp3 destabilization and IL-17 expression
Authors: Nakatsukasa Hiroko , Oda Mayumi , Yin Jinghua , Chikuma Shunsuke , Ito Minako , Koga-Iizuka Mana , Someya Kazue , Kitagawa Yohko , Ohkura Naganari , Sakaguchi Shimon , Koya Ikuko , Sanosaka Tsukasa , Kohyama Jun , Tsukada Yu-ichi , Yamanaka Soichiro , Takamura-Enya Takeji , Lu Qianjin , Yoshimura Akihiko
Published: January 2019

Ten-eleven translocation (TET) proteins regulate DNA methylation and gene expression by converting 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC). Although Tet2/Tet3 deficiency has been reported to lead to myeloid cell, B-cell and invariant natural killer T (iNKT) cell malignancy, the effect of TET on regulatory T cells (Tregs) has not been elucidated. We found that Tet2/Tet3 deficiency in Tregs led to lethal hyperproliferation of CD4+Foxp3+ T cells in the spleen and mesenteric lymph nodes after 5 months of age. Additionally, in aged Treg-specific Tet2/Tet3-deficient mice, serum IgG1, IgG3, IgM and IgE levels were markedly elevated. High IL-17 expression was observed in both Foxp3+ and Fopx3- CD4+ T cells, and adoptive transfer of Tet2/Tet3-deficient Tregs into lymphopenic mice inhibited Foxp3 expression and caused conversion into IL-17-producing cells. However, the conserved non-coding DNA sequence-2 (CNS2) region of the Foxp3 gene locus, which has been shown to be particularly important for stable Foxp3 expression, was only partly methylated. We identified novel TET-dependent demethylation sites in the Foxp3 upstream enhancer, which may contribute to stable Foxp3 expression. Together, these data indicate that Tet2 and Tet3 are involved in Treg stability and immune homeostasis in mice.
The National Cancer Institute Clinical Trials Planning Meeting for Prevention and Treatment of Chemotherapy-Induced Peripheral Neuropathy
Authors: Dorsey Susan G , Kleckner Ian R , Barton Debra , Mustian Karen , O’Mara Ann , St. Germain Diane , Cavaletti Guido , Danhauer Suzanne C , Hershman Dawn L , Hohmann Andrea G , Hoke Ahmet , Hopkins Judith O , Kelly Katherine P , Loprinzi Charles L , McLeod Howard L , Mohile Supriya , Paice Judith , Rowland Julia H , Salvemini Daniela , Segal Rosalind A , Smith Ellen Lavoie , Stevens Worta McCaskill , Janelsins Michelle C
Published: January 2019

Although recent scientific advances have improved our understanding of basic biological mechanisms underlying chemotherapy-induced peripheral neuropathy (CIPN), few interventions are available to prevent or treat CIPN. Although some biological targets from preclinical studies show promise in nonhuman animal models, few targets have been translated to successful clinical trials. To address this problem, the National Cancer Institute’s Symptom Management and Health-Related Quality of Life Steering Committee convened a meeting of experts in the CIPN and oncology symptom management fields to participate in a Clinical Trials Planning Meeting (CTPM). Investigators presented data from preclinical and translational studies for possible CIPN interventions; these were evaluated for readiness of randomized clinical trial testing by experts, and recommendations were provided. Breakout sessions were convened to discuss and develop future studies. The CTPM experts concluded that there is compelling evidence to move forward with selected pharmacological and nonpharmacological clinical trials for the prevention and treatment of CIPN. Several key feasibility issues need to be addressed, however. These include identification of optimal outcome measures to define the CIPN phenotype, establishment of parameters that guide the evaluation of clinically meaningful effects, and adoption of approaches for inclusion of translational and biomarker and/or genetic measures. The results of the CTPM provide support for conducting clinical trials that include both pharmacological and nonpharmacological approaches, alone or in combination, with biomarkers, genetics, or other measures designed to inform underlying CIPN mechanisms. Several working groups were formed to design rigorous CIPN clinical trials, the results of which are ongoing.
Increased virulence of albino mutant of Fonsecaea monophora in Galleria mellonella
Authors: Liu Yinghui , Huang Xiaowen , Liu Hongfang , Xi Liyan , Cooper Chester R
Published: January 2019

Fonsecaea monophora has been the predominant pathogen of chromoblastomycosis in Southern China, but its pathogenic mechanism remains unclear. New models are needed to study this infection. In the current study, we examined the role of melanin on the pathogenicity of F. monophora in Galleria mellonella model using melanin and albino strain. Interestingly, the albino mutant strain displayed higher pathogenicity compared to the melanin stain and restoration of melanin of albino mutant could reverse the pathogenicity. Histopathology showed that inflammatory nodules were bigger than that infected with albino cells, which suggested that melanized cells could trigger a robust cellular immune response of G. mellonella than albino cells. The activated immune response in G. mellonella induced by melanized cells might explain the decreased virulence of melanized cells in larvae model. While further study was needed to gain full insights into the molecular immunological mechanism in G. mellonella activated by melanin.
The Palomar Transient Factory Sky2Night programme
Authors: van Roestel J , Groot P J , Kupfer T , Verbeek K , van Velzen S , Bours M , Nugent P , Prince T , Levitan D , Nissanke S , Kulkarni S R , Laher R R
Published: January 2019

We present results of the Sky2Night project: a systematic, unbiased search for fast optical transients with the Palomar Transient Factory. We have observed 407deg2 in R-band for eight nights at a cadence of 2 h. During the entire duration of the project, the 4.2 m William Herschel Telescope on La Palma was dedicated to obtaining identification spectra for the detected transients. During the search, we found 12 supernovae, 10 outbursting cataclysmic variables, nine flaring M-stars, three flaring active galactic nuclei, and no extragalactic fast optical transients. Using this systematic survey for transients, we have calculated robust observed rates for the detected types of transients, and upper limits of the rate of extragalactic fast optical transients of $\mathcal {R}\lt 37\times 10^{-4}$deg−2 d−1 and $\mathcal {R}\lt 9.3\times 10^{-4}$deg−2 d−1 for time-scales of 4 h and 1 d and a limiting magnitude of R ≈ 19.7. We use the results of this project to determine what kind of and how many astrophysical false positives we can expect when following up gravitational wave detections in search for kilonovae.
The Persistence of Financial Distress
Authors: Athreya Kartik , Mustre-del-Río José , Sánchez Juan M
Published: January 2019

Using proprietary panel data, we show that many U.S. consumers experience financial distress (35% when distress is defined by having debt in severe delinquency, e.g.) at some point in their lives. However, most distress events are concentrated on a much smaller proportion of consumers in persistent trouble: fewer than 10% of borrowers account for half of all distress events. These facts can be largely accounted for in a straightforward extension of a workhorse model of unsecured debt with informal default that accommodates a simple form of heterogeneity in time preference.

Received November 10, 2017; editorial decision November 12, 2018 by Editor Stijn Van Nieuwerburgh.
Speckle Tracking Analysis of Left Ventricular Systolic Function Following Traumatic Brain Injury: A Pilot Prospective Observational Cohort Study
Authors: Krishnamoorthy Vijay , Chaikittisilpa Nophanan , Lee James , Mackensen G. Burkhard , Gibbons Edward F. , Laskowitz Daniel , Hernandez Adrian , Velazquez Eric , Lele Abhijit V. , Vavilala Monica S.
Published: January 2019

Background:

Systolic dysfunction and reduction in left ventricular ejection fraction (LVEF) has been documented after traumatic brain injury (TBI). Speckle tracking is an emerging technology for myocardial strain assessment which has been utilized to identify subclinical myocardial dysfunction, and is most commonly reported as global longitudinal strain (GLS). We examined myocardial strain and regional strain patterns following moderate-severe TBI.

Materials and Methods:

We conducted a prospective cohort study of moderate-severe TBI patients (Glasgow Coma Scale≤12) and age/sex-matched controls. Transthoracic echocardiography was performed within the first day and 1 week following TBI. Myocardial function was assessed using both GLS and LVEF, and impaired systolic function was defined as GLS >−16% or LVEF ≤50%. Regional strain patterns and individual strain trajectories were examined.

Results:

Thirty subjects were included, 15 patients with TBI and 15 age/sex-matched controls. Among patients with adequate echocardiographic windows, systolic dysfunction was observed in 2 (17%) patients using LVEF and 5 (38%) patients using GLS within the first day after TBI. Mean GLS was impaired in patients with TBI compared with controls (−16.4±3.8% vs. −20.7±1.8%, P=0.001). Regional myocardial examination revealed impaired strain primarily in the basal and mid-ventricular segments. There was no improvement in GLS from day 1 to day 7 (P=0.81).

Conclusions:

Myocardial strain abnormalities are common and persist for at least 1 week following moderate-severe TBI. Speckle tracking may be useful for the early diagnosis and monitoring of systolic dysfunction following TBI.
Neuroanesthesiology Update
Authors: Pasternak Jeffrey J.
Published: January 2019

This review provides a summary of the literature pertaining to the perioperative care of neurosurgical patients and patients with neurological diseases. General topics addressed in this review include general neurosurgical considerations, stroke, traumatic brain injury, neuromonitoring, neurotoxicity, and perioperative disorders of cognitive function.
The Relevance of the Judet and Letournel Acetabular Fracture Classification System in the Modern Era: A Review
Authors: Butler Bennet A. , Lawton Cort D. , Hashmi Sohaib Z. , Stover Michael D.
Published: January 2019

The Judet and Letournel acetabular fracture classification system, based on the idea of bicolumnar support of the acetabulum, was first described in a landmark article published in the 1960s. It has stood the test of time and continues to be the preferred method for describing acetabular fractures for the majority of orthopaedic trauma surgeons. Still, there have been attempts to modify or replace Letournel system since its introduction for a variety of reasons, chief among them a perceived inability of the classification system to account for a number of transitional fracture patterns and injury modifiers that may affect surgical decision making and patient outcomes. In this review, we present the literature related to the Judet and Letournel acetabular fracture classification system, over 50 years after its first formal description. We summarize its strengths, weaknesses, and its place in our current understanding of acetabular fractures and their recommended management.
Do We Need a Separate Classification for Fragility Fractures of the Pelvis?
Authors: Rommens Pol Maria , Wagner Daniel , Hofmann Alexander
Published: January 2019

Fragility fractures of the pelvis are occurring with increasing frequency. These fractures, occurring in the geriatric patient population, are low-energy injuries and are dissimilar in many ways from those caused by high-energy trauma. For example, the mechanism of injury is different and emergency treatment is usually not necessary. Having diminished bone strength, fragility fracture lines follow areas of low bone mineral density and loss of pelvic stability may increase over time. Based on our clinical experience, we propose a comprehensive classification of pelvic fragility fractures separate from the existing pelvic ring injury classification to provide a framework for distinguishing the different fragility fracture types and their recommended treatment. This classification is derived first from the degree of fracture instability, followed by the location of the fracture. Anterior pelvic fractures are differentiated from posterior pelvic ring fractures, nondisplaced fractures from displaced, and unilateral from bilateral. It is our belief that this new in-depth analysis of these lesions will assist the clinician in identifying the specific patterns of fragility fracture instability and selecting the appropriate choice of treatment. Further investigation is required to determine the ultimate value of this proposed pelvic fragility fracture classification system.

Level of Evidence:

Diagnostic Level V.
The Ilioinguinal Surgical Approach Using a Modified Medial Window: Origin, Evolution, and Applications. A 34-Year Perspective
Authors: Mayo Keith , Unno Florence
Published: January 2019

Emile Letournel’s ilioinguinal approach provided unprecedented surgical access to the anterior aspect of the innominate bone. A refinement of this approach is described which incorporates a modified medial window that limits dissection around the external iliac vessels, expands surgical exposure of the anterior pelvic ring, and provides additional reduction possibilities while preserving the capabilities of the lateral and middle windows.
Geriatric Acetabular Surgery: Letournel's Contraindications Then and Now—Data From the German Pelvic Registry
Authors: Herath Steven C. , Pott Hendrik , Rollmann Mika F. R. , Braun Benedikt J. , Holstein Jörg H. , Höch Andreas , Stuby Fabian M. , Pohlemann Tim ,   on behalf of the German Pelvic Multicenter Study Group
Published: January 2019

Objective:

In his original series of 129 surgically treated acetabular fractures, Letournel did not operate on patients older than 60 years. Almost 30 years later, he still emphasized that no patients with reduced bone quality should be operated on. The aim of the study was to analyze epidemiologic characteristics and treatment modes for today's cohort of elderly patients with acetabular fractures.

Design:

Retrospective analysis.

Setting:

Multicenter registry/Level I trauma center.

Patients:

Three thousand seven hundred ninety-three patients who had sustained a fracture of the acetabulum.

Intervention:

Operative and nonoperative treatment of acetabular fractures.

Main Outcome Measurements:

Epidemiologic characteristics, treatment mode, in-hospital mortality, rate of secondary hip arthroplasty, and quality of life indicated by EQ-5D score.

Results:

For the multicenter registry, more than 50% of all patients with acetabular fractures had an age of 60 years or over. The age peak was found at 75–80 years. Fifty percent of the elderly patients were treated surgically. The in-hospital mortality was significantly higher in elderly patients than patients younger than 60 years. In our Level I trauma center, surgical treatment by open reduction and internal fixation did not influence in-hospital mortality or quality of life of elderly patients with acetabular fractures.

Conclusions:

Today, elderly persons represent the dominant cohort among patients with fractures of the acetabulum. Fifty-five years after the publication of Letournel's original case series, data indicate that currently, surgical treatment is a common and necessary option in the therapy of acetabular fractures in elderly patients.

Level of Evidence:

Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.
Current Trends in the Surgical Treatment of Open-Book Pelvic Ring Injuries: An International Survey Among Experienced Trauma Surgeons
Authors: Moed Berton R. , Barla Jorge , Israel Heidi A. , Tovar Shandher , Joeris Alexander
Published: January 2019

Introduction:

In the open-book, rotationally unstable (OTA/AO type 61-B1.1) pelvic ring injury, the posterior sacroiliac complex is believed to remain intact. Therefore, anterior ring stabilization alone has been the standard treatment recommendation. However, treatment failures using this method have caused a reconsideration of this management strategy. Anterior plus posterior fixation is the main alternative. In the absence of any specific new guidelines, the choice of treatment currently relies on the preference of the treating surgeon. The objective of this survey was to determine the relative use of anterior plus posterior fixation, as opposed to the standard anterior fixation alone, for the treatment of open-book pelvic ring injuries.

Methods:

An international group of 176 practicing trauma surgeons experienced in pelvic ring fracture fixation participated in an AO Foundation survey asking for their preferred standard surgical fixation (anterior alone or anterior plus posterior combined) for OTA/AO type 61-B1.1 open-book pelvic fractures.

Results:

Anterior plate fixation alone (group 1) was preferred by 56% of the survey participants, and combined anterior plus posterior fixation (group 2) was preferred by 44%. Statistical analysis revealed that group 1 participants were significantly older than group 2 participants (P = 0.03) and had more years of surgical experience (P = 0.02).

Conclusions:

Concern regarding the inadequacy of anterior fixation alone has led many surgeons, especially those more recently in practice, to add posterior fixation, despite limited data to determine its indications. No doubt the OTA/AO type B 1.1 pelvic ring disruption actually represents a wide spectrum of injury. Further study is needed to determine the best fixation method.
The Role of the Computed Tomographic Scan in the Diagnosis of Acetabular Fracture in the Immature Pelvis
Authors: Shaath M. Kareem , Ippolito Joseph A. , Adams Mark R. , Sirkin Michael S. , Reilly Mark C.
Published: January 2019

Objectives:

We present a series of skeletally immature patients sustaining acetabular fractures. We hypothesized that if the secondary ossification centers of the acetabulum are not completely ossified, fractures often will not be identified on plain radiography. Our objective was to determine the efficacy of diagnostic plain radiography in these patients.

Design:

Retrospective case series.

Setting:

Urban, level-I trauma center.

Patients/Participants:

Skeletally immature patients with acetabular fractures following blunt force trauma.

Intervention:

We obtained a dedicated axial computed tomographic (CT) scan of the pelvis with sequential sections of 2.5-mm thickness.

Main Outcome Measures:

The accuracy of plain radiography as compared with CT in diagnosing acetabular fractures in skeletally immature patients.

Results:

Fourteen patients with 16 fractures of the acetabulum were identified by CT scan; however, 69% (11 of 16) were not visible on plain radiography. Radiographs were less likely to identify acetabular fractures compared with pelvic ring fractures [31% (5/16) vs. 92% (11/12); odds ratio, 0.04; 95% confidence interval, 0.01–0.37; P = 0.001]. Patients younger than 12 years were less likely to have acetabular fractures identified on plain radiography [9% (1/11) vs. 80% (4/5); odds ratio, 0.03; 95% confidence interval 0.01–0.59; P = 0.013]. The mean age of patients whose acetabular fractures were not identified on plain radiography was less than those whose fractures were identified on plain radiography (7.6 ± 2.9 vs. 12.8 ± 1.6; P = 0.004). Acetabular fractures visible on plain radiography were more likely to require operative stabilization [60% (3/5) vs. 0% (0/11); P = 0.004].

Conclusions:

In skeletally immature patients with suspected injury to the pelvis, particularly in patients younger than 12 years, diagnostic evaluation using plain radiographs alone may lead to missed injuries. If an acetabular fracture is identified, patients should be followed closely both clinically and radiographically to ensure early identification of any developing posttraumatic deformity.

Level of Evidence:

Level IV; Diagnostic—Investigating a diagnostic test.
Combined Pelvic Ring Disruption and Acetabular Fracture: Outcomes Using a Sequential Reduction Protocol and an Anterior Subcutaneous Pelvic Fixator (INFIX)
Authors: Vaidya Rahul , Blue Kevin , Oliphant Bryant , Tonnos Fred
Published: January 2019

Objective:

The purposes of this article were to (1) compare our combined pelvic ring and acetabular fracture patients' rate of mortality and Injury Severity Score (ISS) to those of patients with isolated injuries at our center and to those with combined injuries as reported in the literature, (2) describe our treatment algorithm using the INFIX for these combination injuries, and (3) report our patients' radiographic and functional outcomes.

Design:

Retrospective IRB-approved case series and literature review.

Setting:

US Level 1 Trauma Center.

Patients/Participants:

Thousand six hundred ninety-seven with acetabular or pelvic ring injury, 174 patients with combination pelvic ring acetabular injuries, and 39 patients with 41 acetabular injuries treated with a surgical protocol.

Intervention:

Pelvic ring reduction using INFIX and posterior fixation followed by acetabular reduction fixation. Anterior injury fixed with INFIX.

Main Outcome:

Mortality, ISS, pelvic reduction by Keshishyan index, acetabular reduction by the Matta criteria, and functional outcome by the Majeed score.

Results:

Mortality was 5.7% and ISS was 12.5 for 174 combined injury patients. In the 39 patients with 41 injuries, excellent pelvic reduction was found in 39, and acetabular reduction was anatomic in 25 (61%), imperfect in 12 (29%), and poor in 4 (10%). Clinically 78% of the patients had good or excellent outcome and 22% had a fair or poor outcome. Nonanatomic acetabular reduction, persistent sciatic nerve palsy, and heterotopic ossification associated with poor clinical outcome.

Conclusions:

Our treatment protocol resulted in excellent pelvic reduction, anatomic acetabular reduction in 61% of patients, and 78% good to excellent clinical outcome.

Level of Evidence:

Case series Level IV.
Ultrasonographic changes of labrum morphology in patients with developmental dysplasia of the hip: a preliminary report on 74 dysplastic and unstable hips
Authors: De Pellegrin Maurizio , Montanari Lucrezia , Moharamzadeh Désirée , Fracassetti Dario
Published: January 2019

The aim of the study was to verify the labrum’s morphological changes in unstable and dysplastic hips during treatment. Between January 2013 and April 2015, 74 dysplastic hips were divided into type D (n=12), type III (n=40), and type IV (n=22). The labrum was evaluated on ultrasonography (US) for echogenicity and dimensions with interobserver/intraobserver tests: test 1 (US at diagnosis and control group), test 2 (US at diagnosis and 6 weeks post-treatment), and test 3 (US at diagnosis and at end of treatment). Statistical analysis was performed. The labrum was less echogenic in test 1 and more echogenic in test 3, and the labrum was smaller in test 1 and larger in test 3. The labrum undergoes statistically significant increase of echogenicity and dimensions after treatment, suggesting a stabilizing role. Level of Evidence: Level II, Oxford Center for Evidence-based Medicine.
Pediatric acute compartment syndrome: a systematic review and meta-analysis
Authors: Lin James S. , Samora Julie Balch
Published: January 2019

Acute compartment syndrome (ACS) is an emergency with potentially devastating consequences. Delayed recognition may be especially concerning for the pediatric population, as children present with a wide variety of etiologies, symptoms, and levels of communication. We sought to determine the average time from injury to diagnosis, most common presentations, the degree to which providers obtained pressure measurements, and outcomes of ACS in the pediatric population. We performed a systematic review of multiple databases to include English-language clinical studies reporting ACS of the extremity in pediatric patients. Review articles, studies lacking statistical data, single case reports, and other evidence level V studies were excluded. Twelve studies were included, with all reporting clinical outcomes following diagnosis and intervention of ACS in children. There were 233 children with an average age of 9.7 years (SD: 5.9 years, range: 0–18 years). The most common causes were trauma-related: pedestrian versus motor vehicles (21%), motor vehicle accidents (12%), falls (12%), and sports/exercise-related injuries (12%). ACS occurred in all extremities, with lower leg (60%) and forearm (27%) being most common. Seventy-five percent of patients had concomitant fractures. Compartment pressures were measured in 68% of patients to aid diagnosis. Pain was the most common presenting symptom (88%) followed by paresthesias (32%). The mean time from injury to fasciotomy was 25.4 h. Patients had good outcomes, with 85% achieving full functional recovery. Range of motion deficit (10%) was the most common complication. We detected no significant difference in time from injury to fasciotomy, age, sex, the presence of a fracture, or anatomic location in those patients who achieved full functional recovery compared with patients who did not. Pediatric ACS occurs most often in the setting of trauma. Intracompartmental pressure measurements can aid diagnosis. Pediatric ACS differs from adult ACS, as pediatric patients generally achieve good outcomes even when presenting in delayed fashion and undergoing fasciotomies for at least 24 h. We recommend considering decompressive fasciotomy in children even if there is prolonged time from injury to diagnosis. Level of evidence: IV.
Use of Gabapentin in Posterior Spinal Fusion is Associated With Decreased Postoperative Pain and Opioid Use in Children and Adolescents
Authors: Trzcinski Stacey , Rosenberg Rebecca E. , Vasquez Montes Dennis , Sure Akhila , Zhou Peter , Tishelman Jared , Mansky Robert , McLeod Lisa , Tracy Joanna , Buckland Aaron J. , Errico Thomas J.
Published: January 2019

Study Design:

Retrospective cohort study.

Objective:

The objective of this study was to examine associations of gabapentin use with inpatient postoperative daily pain scores and opioid use in children undergoing PSF for AIS.

Summary of Background Data:

Gabapentin use in posterior spinal fusion (PSF) postoperative pain management for adolescent idiopathic scoliosis (AIS) is increasingly common in order to decrease opioid use and improve pain control, though there is conflicting data on dosing and effectiveness to support this practice in real world settings.

Methods:

Retrospective cohort study of children aged 10 to 21 years undergoing PSF for AIS between January 2013 and June 2016 at an urban academic tertiary care center. Adjuvant gabapentin exposure was defined as at least 15 mg/kg/d by postoperative day (POD) 1 with an initial loading dose of 10 mg/kg on day of surgery. Primary outcomes were daily postoperative mean pain score and opioid use [morphine milligram equivalents/kg/day(mme/kg/d)]. Secondary outcomes were short and long-term complications.

Results:

Among 129 subjects (mean age, 14.6 y, 74% female, mean coronal cobb, 55.2 degrees), 24 (19%) received gabapentin. Unadjusted GABA exposure was associated with significantly lower opioid use on POD1 and 2 (49% and 31%mme/kg/d, respectively) and lower pain scores (14%) on POD2. Adjusting for preexisting back pain, preoperative coronal Cobb angle, and site, GABA use was associated with significantly lower mean pain scores on POD1 through POD3 (−0.68, P=0.01; −0.86, P=0.002; −0.63, P=0.04). Gabapentin use was also associated with decreased opioid use on POD1 and POD2 (−0.39mme/kg/d, P<0.001; −0.27, P=0.02). There was no difference in complications by gabapentin exposure.

Conclusions:

Addition of gabapentin as adjuvant therapy for adolescent PSF, beginning on day of surgery, is associated with improved pain scores and decreased opioid use in the first 48 to 72 hours postoperatively.

Level of Evidence:

This is a retrospective cohort study, classified as Level III under “Therapeutic Studies Investigating the Results of a Treatment.”
Evaluating Tele-ICU Implementation Based on Observed and Predicted ICU Mortality: A Systematic Review and Meta-Analysis*
Authors: Fusaro Mario V. , Becker Christian , Scurlock Corey
Published: January 2019

Objectives:

Past studies have examined numerous components of tele-ICU care to decipher which elements increase patient and institutional benefit. These factors include review of the patient chart within 1 hour, frequent collaborative data reviews, mechanisms for rapid laboratory/alert review, and interdisciplinary rounds. Previous meta-analyses have found an overall ICU mortality benefit implementing tele-ICU, however, subgroup analyses found few differences. The purpose of this systematic review and meta-analysis was to explore the effect of tele-ICU implementation with regard to ICU mortality and explore subgroup differences via observed and predicted mortality.

Data Sources:

We searched PubMed, Cochrane Library, Embase, and European Society of Intensive Care Medicine for articles related to tele-ICU from inception to September 18, 2018.

Study Selection:

We included all trials meeting inclusion criteria which looked at the effect of tele-ICU implementation on ICU mortality.

Data Extraction:

We abstracted study characteristics, patient characteristics, severity of illness scores, and ICU mortality rates.

Data Synthesis:

We included 13 studies from 2,766 abstracts identified from our search strategy. The before-after tele-ICU implementation pooled odds ratio for overall ICU mortality was 0.75 (95% CI, 0.65–0.88; p < 0.001). In subgroup analysis, the pooled odds ratio for ICU mortality between the greater than 1 versus less than 1 observed to predicted mortality ratios was 0.64 (95% CI, 0.52–0.77; p < 0.001) and 0.98 (95% CI, 0.81–1.18; p = 0.81), respectively. Test for interaction was significant (p = 0.002).

Conclusions:

After evaluating all included studies, tele-ICU implementation was associated with an overall reduction in ICU mortality. Subgroup analysis suggests that publications exhibiting observed to predicted ICU mortality ratios of greater than 1 before tele-ICU implementation was associated with a reduction in ICU mortality after tele-ICU implementation. No significant ICU mortality reduction was noted in the subgroup of observed to predicted ICU mortality ratio less than 1 before tele-ICU implementation. Future studies should confirm this finding using patient-level data.
Workforce, Workload, and Burnout Among Intensivists and Advanced Practice Providers: A Narrative Review
Authors: Pastores Stephen M. , Kvetan Vladimir , Coopersmith Craig M. , Farmer J. Christopher , Sessler Curtis , Christman John W. , D’Agostino Rhonda , Diaz-Gomez Jose , Gregg Sara R. , Khan Roozehra A. , Kapu April N. , Masur Henry , Mehta Gargi , Moore Jason , Oropello John M. , Price Kristen
Published: January 2019

Objectives:

To assess—by literature review and expert consensus—workforce, workload, and burnout considerations among intensivists and advanced practice providers.

Design:

Data were synthesized from monthly expert consensus and literature review.

Setting:

Workforce and Workload section workgroup of the Academic Leaders in Critical Care Medicine Task Force.

Measurements and Main Results:

Multidisciplinary care teams led by intensivists are an essential component of critical care delivery. Advanced practice providers (nurse practitioners and physician assistants) are progressively being integrated into ICU practice models. The ever-increasing number of patients with complex, life-threatening diseases, concentration of ICU beds in few centralized hospitals, expansion of specialty ICU services, and desire for 24/7 availability have contributed to growing intensivist staffing concerns. Such staffing challenges may negatively impact practitioner wellness, team perception of care quality, time available for teaching, and length of stay when the patient to intensivist ratio is greater than or equal to 15. Enhanced team communication and reduction of practice variation are important factors for improved patient outcomes. A diverse workforce adds value and enrichment to the overall work environment. Formal succession planning for ICU leaders is crucial to the success of critical care organizations. Implementation of a continuous 24/7 ICU coverage care model in high-acuity, high-volume centers should be based on patient-centered outcomes. High levels of burnout syndrome are common among intensivists. Prospective analyses of interventions to decrease burnout within the ICU setting are limited. However, organizational interventions are felt to be more effective than those directed at individuals.

Conclusions:

Critical care workforce and staffing models are myriad and based on several factors including local culture and resources, ICU organization, and strategies to reduce burden on the ICU provider workforce. Prospective studies to assess and avoid the burnout syndrome among intensivists and advanced practice providers are needed.
Effect of Antihypertensive Medications on Sepsis-Related Outcomes: A Population-Based Cohort Study*
Authors: Kim Joohae , Kim Young Ae , Hwangbo Bin , Kim Min Jeong , Cho Hyunsoon , Hwangbo Yul , Lee Eun Sook
Published: January 2019

Objectives:

Although the effect of antihypertensive agents on sepsis has been studied, evidence for survival benefit was limited in the literature. We investigated differences in sepsis-related outcomes depending on the antihypertensive drugs given prior to sepsis in patients with hypertension.

Design:

Population-based cohort study.

Setting:

Sample cohort Database of the National Health Insurance Service from 2003 to 2013 in South Korea.

Patients:

Patients over 30 years old who were diagnosed with sepsis after receiving hypertension treatment.

Interventions:

None.

Measurements and Main Results:

Primary outcomes, 30-day and 90-day mortality rates, were analyzed for differences among three representative antihypertensive medications: angiotensin- converting enzyme inhibitors or angiotensin II receptor blockers, calcium channel blockers, and thiazides. In total, 4,549 patients diagnosed with hypertension prior to hospitalization for sepsis were identified. The 30-day mortality was significantly higher among patients who did not receive any medications within 1 month before sepsis (36.8%) than among patients who did (32.0%; p < 0.001). The risk for 90-days mortality was significantly lower in prior angiotensin-converting enzyme inhibitors or angiotensin II receptor blocker users (reference) than in other drug users (odds ratio, 1.27; 95% CI, 1.07–1.52). There was no difference in the risk for 30-day and 90-day mortality depending on whether calcium channel blockers or thiazides were used. Use of calcium channel blockers was associated with a decreased risk for inotropic agent administration, compared with those of angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers (odds ratio, 1.23; 95% CI, 1.05–1.44) and thiazides (odds ratio, 1.33; 95% CI, 1.12–1.58).

Conclusions:

In patients with sepsis, lower mortality rate was associated with prior use of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers not with use of calcium channel blockers or thiazides. The requirement of inotropic agents was significantly lower in prior use of calcium channel blockers, although the survival benefits were not prominent.
Immunotargeted therapy in melanoma: patient, provider preferences, and willingness to pay at an academic cancer center
Authors: Stenehjem David D. , Au Trang H. , Ngorsuraches Surachat , Ma Junjie , Bauer Hillevi , Wanishayakorn Tanatape , Nelson Ryan S. , Pfeiffer Constance M. , Schwartz Joshua , Korytowsky Beata , Oderda Gary , Brixner Diana I.
Published: January 2019

New melanoma therapies have shifted the expectations of patients and providers. Evaluating the impact of treatment characteristics may enhance shared decision making. A survey, including a discrete choice experiment, was utilized to evaluate perceived trade-offs of different melanoma treatments and to estimate out-of-pocket (OOP) willingness-to-pay (WTP) thresholds (January 2016 to March 2016). Participants included patients with melanoma at Huntsman Cancer Institute and their cancer care providers. Stakeholder focus groups were conducted to identify treatment attributes. Descriptive and comparative statistics and multinomial logit model were used to evaluate responses. Response rates were 41.9% (N = 220) for patients and 37.7% (N = 20) for providers. Immunotherapy and targeted therapy attributes considered important by participants were overall survival, immunotherapy-related side effects, and skin toxicities. Patients and providers had significantly different views of quality-of-life expectations, anxiety toward melanoma, trust to make treatment decisions, sharing concerns about treatment, time to discuss treatment, understanding OOP costs, and willingness to undergo/recommend treatment (half of the patients would undergo treatment if it was effective for > 24 months). Among patients, the average monthly OOP WTP for combination immunotherapy with nivolumab + ipilimumab was $ 2357 and for BRAF/MEK inhibitor was $1648. Among providers, these estimates were $ 2484 and $1350, respectively. Discordance existed between patients’ and providers’ perceptions about quality of life expectations, degree of anxiety, sharing of opinions, and progression-free survival. Our study suggests that patients and providers exhibit a higher OOP WTP for combination immunotherapy treatment compared with BRAF/MEK inhibitors, influenced predominately by overall survival expectations.
Melanoma susceptibility variant rs869330 in the MTAP gene is associated with melanoma outcome
Authors: Marasigan Vivien , Güvenç Canan , van den Oord Joost J. , Stas Marguerite , Boecxstaens Veerle , Bechter Oliver , Wolter Pascal , Lambrechts Diether , Garmyn Marjan
Published: January 2019

The rising incidence of cutaneous melanoma (CM), an aggressive skin cancer, emphasizes the need for novel biomarkers to guide personalized care and better predict outcome. Genetic factors including germline risk variants are promising candidates for this aim. We explored the association between germline risk variants and melanoma outcome in a large genetically homogenous Belgian melanoma population, focusing on single nucleotide polymorphisms which generated the highest association with melanoma susceptibility. Between 2004 and 2014, blood samples of 1088 patients with histologically confirmed CM were collected and genotyped for nine variants. Cox proportional hazard models were used to assess the association between each single nucleotide polymorphism and relapse-free survival and overall survival, adjusted by age, sex, melanoma stage, site, and subtype. We identified significant associations for rs869330 (in the methylthioadenosine phosphorylase – MTAP gene) with overall survival (hazard ratio = 0.760, P = 0.048, 95% confidence interval: 0.580–0.998) and relapse-free survival (hazard ratio = 0.800, P = 0.020, 95% confidence interval: 0.650–0.970). This exploratory study is the first to show a significant association between the rs869330 variant (in the MTAP gene) and outcome in a large CM population.