bluuebunny/crossref_metadata_2025_split huggingface dataset:
Restrictive versus Liberal Transfusion Strategy in the Perioperative and Acute Care Settings
Authors: Hovaguimian Frédérique , Myles Paul S. 
Published: May 2016

AbstractAbstract
In a review of 31 trials grouped into 5 context-specific strata, restrictive transfusion strategies increased the risk of mortality and composite morbidity in patients undergoing cardiac/vascular procedures and in elderly orthopedic patients.
Supplemental Digital Content is available in the text.

Background
Blood transfusions are associated with morbidity and mortality. However, restrictive thresholds could harm patients less able to tolerate anemia. Using a context-specific approach (according to patient characteristics and clinical settings), the authors conducted a systematic review to quantify the effects of transfusion strategies.

Methods
The authors searched MEDLINE, EMBASE, CENTRAL, and grey literature sources to November 2015 for randomized controlled trials comparing restrictive versus liberal transfusion strategies applied more than 24 h in adult surgical or critically ill patients. Data were independently extracted. Risk ratios were calculated for 30-day complications, defined as inadequate oxygen supply (myocardial, cerebral, renal, mesenteric, and peripheral ischemic injury; arrhythmia; and unstable angina), mortality, composite of both, and infections. Statistical combination followed a context-specific approach. Additional analyses explored transfusion protocol heterogeneity and cointerventions effects.

Results
Thirty-one trials were regrouped into five context-specific risk strata. In patients undergoing cardiac/vascular procedures, restrictive strategies seemed to increase the risk of events reflecting inadequate oxygen supply (risk ratio [RR], 1.09; 95% CI, 0.97 to 1.22), mortality (RR, 1.39; 95% CI, 0.95 to 2.04), and composite events (RR, 1.12; 95% CI, 1.01 to 1.24—3322, 3245, and 3322 patients, respectively). Similar results were found in elderly orthopedic patients (inadequate oxygen supply: RR, 1.41; 95% CI, 1.03 to 1.92; mortality: RR, 1.09; 95% CI, 0.80 to 1.49; composite outcome: RR, 1.24; 95% CI, 1.00 to 1.54—3465, 3546, and 3749 patients, respectively), but not in critically ill patients. No difference was found for infections, although a protective effect may exist. Risk estimates varied with successful/unsuccessful transfusion protocol implementation.

Conclusions
Restrictive transfusion strategies should be applied with caution in high-risk patients undergoing major surgery.
Varicella zoster virus triggers the immunopathology of giant cell arteritis
Authors: Gilden Don , Nagel Maria A. 
Published: May 2016

Purpose of review
Giant cell arteritis (GCA) is a severe form of vasculitis in the elderly. The recent discovery of varicella zoster virus (VZV) in the temporal arteries and adjacent skeletal muscle of patients with GCA, and the rationale and strategy for antiviral and corticosteroid treatment for GCA are reviewed.

Recent findings
The clinical features of GCA include excruciating headache/head pain, often with scalp tenderness, a nodular temporal arteries and decreased temporal artery pulsations. Jaw claudication, night sweats, fever, malaise, and a history of polymyalgia rheumatica (aching and stiffness of large muscles primarily in the shoulder girdle, upper back, and pelvis without objective signs of weakness) are common. ESR and CRP are usually elevated. Diagnosis is confirmed by temporal artery biopsy which reveals vessel wall damage and inflammation, with multinucleated giant cells and/or epithelioid macrophages. Skip lesions are common. Importantly, temporal artery biopsies are pathologically negative in many clinically suspect cases. This review highlights recent virological findings in temporal arteries from patients with pathologically verified GCA and in temporal arteries from patients who manifest clinical and laboratory features of GCA, but whose temporal artery biopsies (Bx) are pathologically negative for GCA (Bx-negative GCA). Virological analysis revealed that VZV is present in most GCA-positive and GCA-negative temporal artery biopsies, mostly in skip areas that correlate with adjacent GCA pathology.

Summary
The presence of VZV in Bx-positive and Bx-negative GCA temporal arteries indicates that VZV triggers the immunopathology of GCA. However, the presence of VZV in about 20% of temporal artery biopsies from non-GCA postmortem controls also suggests that VZV alone is not sufficient to produce disease. Treatment trials should be performed to determine if antiviral agents confer additional benefits to corticosteroids in both Bx-positive and Bx-negative GCA patients. These studies should also examine whether oral antiviral agents and corticosteroids are as effective as intravenous acyclovir and corticosteroids. Appropriate dosage and duration of treatment also remain to be determined.
Ankylosing spondylitis: beyond genome-wide association studies
Authors: O’Rielly Darren D. , Uddin Mohammed , Rahman Proton 
Published: May 2016

Purpose of review
This article discusses genomic investigations in ankylosing spondylitis (AS) beyond genome-wide association (GWA) studies, but prior to this, genetic variants achieving genome-wide significance will be summarized highlighting key pathways contributing to disease pathogenesis.

Recent findings
Evidence suggests that disease pathogenesis is attributed to a complex interplay of genetic, environmental and immunological factors. GWA studies have greatly enhanced our understanding of AS pathogenesis by illuminating distinct immunomodulatory pathways affecting innate and acquired immunity, most notably the interleukin-23/interleukin-17 pathway. However, despite the wealth of new information gleaned from such studies, a fraction of the heritability (24.4%) has been explained. This review will focus on investigations beyond GWA studies including copy number variants, gene expression profiling, including microRNA (miRNA), epigenetics, rare variants and gene–gene interactions.

Summary
To address the ‘missing heritability’ and advance beyond GWA studies, a concerted effort involving rethinking of study design and implementation of newer technologies will be required. The coming of age of next-generation sequencing and advancements in epigenetic and miRNA technologies, combined with familial-focused investigations using well-characterized cohorts, is likely to reveal some of the hidden genomic mysteries associated with AS.
The interaction between host genetics and the microbiome in the pathogenesis of spondyloarthropathies
Authors: Asquith Mark , Rosenbaum James T. 
Published: May 2016

Purpose of review
The intestinal microbiome is increasingly implicated in the pathogenesis of ankylosing spondylitis, reactive arthritis, and other diseases collectively known as the spondyloarthropathies (SpAs). In common with other complex inflammatory diseases, SpAs have both a strong genetic and environmental component. Recent genetic studies have highlighted host pathways that may intersect the host–microbiota interaction and offer novel paradigms to understand the pathophysiology of these diseases.

Recent findings
Genetic association studies have identified genes such as RUNX3, PTPEN2, and IL-33 as susceptibility loci for SpAs. Functional studies in humans have extended knowledge of established genetic risk factors for ankylosing spondylitis that include ERAP1, ERAP2, and interleukin-23R. Recent basic research has identified new mechanisms that regulate host immune responses to the microbiota that conceivably may be dysregulated in SpA.

Summary
Intestinal barrier function, deletional tolerance, Th17 signature response, and endoplasmic reticulum stress pathways have been recently linked to SpA. Dysregulated immune responses to the gut microbiota and an altered microbial community structure are shared features of SpA. Although the cause-effect dynamic of this relationship remains equivocal, it nonetheless has major implications for both intestinal and extra-intestinal pathology observed in SpA.
FRAX updates 2016
Authors: McCloskey Eugene V. , Harvey Nicholas C. , Johansson Helena , Kanis John A. 
Published: May 2016

Purpose of reviewIn the 8 years since the launch of the FRAX tool, it has continued to grow with the addition of new country or territory models. Although the core of the fracture risk algorithm remains unchanged, there is growing evidence of possible additional independent clinical variables that might modulate the interpretation of the FRAX outputs. There is also an expanding number of international guidelines that incorporate FRAX assessments, leading to discussions on the use of FRAX in treated patients and the determination of intervention thresholds.Recent findingsThis review encompasses recent information on the use of FRAX in immigrant populations and the potential influence of skeletal and extraskeletal risk factors on FRAX estimations. For example, trabecular bone score and falls risk appear to be promising additional factors in individual risk assessment. FRAX appears to remain accurate in those on osteoporosis treatments, but FRAX is not a suitable tool for use in treat-to-target strategies.SummaryThe assessment of fracture risk in immigrants is probably more accurate with the use of the FRAX tool for the country of origin, if available. The impact of additional risk variables will need evaluation of the impact of these on recharacterizing patients by moving them across intervention thresholds.
Do Lumbar Decompression and Fusion Patients Recall Their Preoperative Status?
Authors: Aleem Ilyas S. , Duncan Jonathan , Ahmed Amin M. , Zarrabian Mohammad , Eck Jason , Rhee John , Clarke Michelle , Currier Bradford L. , Nassr Ahmad 
Published: May 2016

Study Design.
Prospective cohort study.

Objective.
To characterize the accuracy of patient recollection of preoperative symptoms after lumbar spine surgery.

Summary of Background Data.
Although patient-reported outcomes have become important in the evaluation of spine surgery patients, the accuracy of patient recall remains unknown.

Methods.
Patients undergoing lumbar decompression with or without fusion were enrolled. Back and leg Numeric Pain Scores and Oswestry Disability Indices were recorded preoperatively. Patients were asked to recall their preoperative status at a minimum of 1 year after surgery. Actual and recalled scores were compared using paired t tests and relations were quantified using Pearson correlation coefficients. Multivariable linear regression was used to identify factors that affected recollection.

Results.
Sixty-two patients with a mean age of 66.1 years were included. Compared to their preoperative scores, patients showed significant improvement in back pain (mean difference [MD] = −3.2, 95% CI −4.0 to −2.4), leg pain (MD −3.3, 95% CI −4.3 to −2.2), and disability (MD −25.0%, 95% CI −28.7 to −19.6). Patient recollection of preoperative status was significantly more severe than actual for back pain (MD +2.3, 95% CI 1.5–3.2), leg pain (MD +1.8, 95% CI 0.9–2.7), and disability (MD +9.6%, 95% CI 5.6–14.0). No significant correlation between actual and recalled scores with regards to back (r = 0.18) or leg (r = 0.24) pain and only moderate correlation with disability (r = 0.44) were seen. This was maintained across age, sex, and time between date of surgery and recollection. More than 40% of patients switched their predominant symptom from back pain to leg pain or leg pain to back pain on recall.

Conclusion.
Relying on patient recollection does not provide an accurate measure of preoperative status after lumbar spine surgery. Recall bias indicates the importance of obtaining true baseline scores and patient-reported outcomes prospectively and not retrospectively.

Level of Evidence: 2
Wedge-Shaped Resection of the Posterior Bony Arch During Open Door Laminoplasty to Prevent Postoperative Motion Limitation
Authors: Suh Bo-Gun , Ahn Myun-Whan , Kim Ho-Joong , Yeom Jin S. , Lee Gun Woo 
Published: May 2016

Study Design.
Prospective randomized double-arm noninferiority study.

Objective.
To evaluate an additional surgical procedure (wedge-shaped resection of the cranial portion of the posterior bony arch) during open-door laminoplasty (ODLP), and to compare the outcomes with those of conventional ODLP surgery.

Summary of Background Data.
In clinical practice, spine surgeons sometimes encounter patients who show bony impingement on lateral radiographs after ODLP; bony impingement may lead to reduced motion of the cervical spine and posterior neck pain. However, this problem has not been well studied, and no methods have been developed to prevent it.

Methods.
Of total 79 patients, 75 were enrolled and randomly assigned to either group A (additional procedure in ODLP, n = 38) or group B (ODLP alone, n = 37). The primary outcome measure was range of motion (ROM) of the cervical spine. Secondary endpoints included clinical outcomes based on pain intensity, 12-item short form health survey (SF-12), and modified Japanese Orthopedic Association scale; presence of bony impingement on dynamic lateral radiographs; surgical outcomes; and surgery-related complications.

Results.
ROM of the cervical spine was significantly greater at 6 months (P = 0.04) and 1 year (P = 0.02) postoperative in group A than in group B. Pain intensity at the posterior neck was significantly lower 1 year after surgery in group A than in group B (P = 0.03). In lateral radiographs 1 year after surgery, the presence of posterior bony impingement was 0% in group A and 32.4% in group B (P <0.01). Clinical outcomes and surgery-related complications were similar between groups.

Conclusion.
Performing wedge-shaped resection of the cranial portion of the posterior bony arch in ODLP surgery can lead to better outcomes than ODLP alone in terms of preservation of cervical ROM, prevention of posterior bony impingement, and amelioration of posterior neck pain.

Level of Evidence: 2
Effect of Inhaled Nitric Oxide on Outcomes in Children With Acute Lung Injury: Propensity Matched Analysis From a Linked Database*
Authors: Gupta Punkaj , Richardson Troy , Hall Matthew , Bertoch David , Hebbar Kiran B. , Fortenberry James D. , Wetzel Randall C. 
Published: May 2016

Objectives:To evaluate the effect of inhaled nitric oxide on outcomes in children with acute lung injury.Design:Retrospective study with a secondary data analysis of linked data from two national databases. Propensity score matching was performed to adjust for potential confounding variables between patients who received at least 24 hours of inhaled nitric oxide (inhaled nitric oxide group) and those who did not receive inhaled nitric oxide (no inhaled nitric oxide group).Setting:Linked data from Virtual Pediatric Systems (LLC) database and Pediatric Health Information System.Patients:Patients less than 18 years old receiving mechanical ventilation for acute lung injury at nine participating hospitals were included (2009–2014).Interventions:None.Measurements and Main Results:A total of 20,106 patients from nine hospitals were included. Of these, 859 patients (4.3%) received inhaled nitric oxide for at least 24 hours during their hospital stay. Prior to matching, patients in the inhaled nitric oxide group were younger, with more comorbidities, greater severity of illness scores, higher prevalence of cardiopulmonary resuscitation, and greater resource utilization. Before matching, unadjusted outcomes, including mortality, were worse in the inhaled nitric oxide group (inhaled nitric oxide vs no inhaled nitric oxide; 25.7% vs 7.9%;p< 0.001; standardized mortality ratio, 2.6 [2.3–3.1] vs 1.1 [1.0–1.2];p< 0.001). Propensity score matching of 521 patient pairs revealed no difference in mortality in the two groups (22.3% vs 20.2%;p= 0.40; standardized mortality ratio, 2.5 [2.1–3.0] vs 2.3 [1.9–2.8];p= 0.53). However, the other outcomes such as ventilation free days (10.1 vs 13.6 d;p< 0.001), duration of mechanical ventilation (13.8 vs 10.1 d;p< 0.001), duration of ICU and hospital stay (15.5 vs 12.2 d;p< 0.001 and 28.0 vs 24.1 d;p< 0.001), and hospital costs ($150,569 vs $102,823;p< 0.001) were significantly worse in the inhaled nitric oxide group.Conclusions:This large observational study demonstrated that inhaled nitric oxide administration in children with acute lung injury was not associated with improved mortality. Rather, it was associated with increased hospital utilization and hospital costs.
Employment Outcomes After Critical Illness: An Analysis of the Bringing to Light the Risk Factors and Incidence of Neuropsychological Dysfunction in ICU Survivors Cohort*
Authors: Norman Brett C. , Jackson James C. , Graves John A. , Girard Timothy D. , Pandharipande Pratik P. , Brummel Nathan E. , Wang Li , Thompson Jennifer L. , Chandrasekhar Rameela , Ely E. Wesley 
Published: May 2016

Objectives:
To characterize survivors’ employment status after critical illness and to determine if duration of delirium during hospitalization and residual cognitive function are each independently associated with decreased employment.

Design:
Prospective cohort investigation with baseline and in-hospital clinical data and follow-up at 3 and 12 months.

Setting:
Medical and surgical ICUs at two tertiary-care hospitals.

Patients:
Previously employed patients from the Bringing to Light the Risk Factors and Incidence of Neuropsychological Dysfunction in ICU Survivors study who survived a critical illness due to respiratory failure or shock were evaluated for global cognition and employment status at 3- and 12-month follow-up.

Measurements and Main Results:
We used multivariable logistic regression to evaluate independent associations between employment at both 3 and 12 months and global cognitive function at the same time point, and delirium during the hospital stay. At 3-month follow-up, 113 of the total survival cohort of 448 (25%) were identified as being employed at study enrollment. Of these, 94 survived to 12-month follow-up. At 3- and 12-month follow-up, 62% and 49% had a decrease in employment, 57% and 49% of whom, respectively, were newly unemployed. After adjustment for physical health status, depressive symptoms, marital status, level of education, and severity of illness, we did not find significant predictors of employment status at 3 months, but better cognition at 12 months was marginally associated with lower odds of employment reduction at 12 months (odds ratio, 0.49; p = 0.07).

Conclusions:
Reduction in employment after critical illness was present in the majority of our ICU survivors, approximately half of which was new unemployment. Cognitive function at 12 months was a predictor of subsequent employment status. Further research is needed into the potential relationship between the impact of critical illness on cognitive function and employment status.
First-line treatment in advanced or metastatic disease: one size fits all or adapted to specific histiotypes?
Authors: Seddon Beatrice 
Published: May 2016

Purpose of review
This article evaluates the supporting evidence for adapting choice of first-line chemotherapy to specific histological subtypes in advanced or metastatic soft tissue sarcoma (STS).

Recent findings
The evidence for the current standard of care for first-line chemotherapy in STS is reviewed. This is followed by an overview of the evidence for use of specific chemotherapy drugs in a number of specific STS histological subtypes. The more recent literature on newer drugs being used in the first-line setting in STS is then reviewed, and finally an assessment is made as to whether it is possible at this time to tailor first-line chemotherapy to histiotype.

Summary
The review shows that at present there is insufficient evidence to support the concept of adapting choice of first-line chemotherapy in advanced or metastatic STS to specific histiotypes.
Molecular subtypes of gastrointestinal stromal tumor requiring specific treatments
Authors: Pogorzelski Michael , Falkenhorst Johanna , Bauer Sebastian 
Published: May 2016

Purpose of review
This article reviews and discusses the current literature on how molecular subtyping of gastrointestinal stromal tumor (GIST) impacts decision-making in clinical practice.

Recent findings
Genotyping has not yet been used for prognostication of localized GIST. Recent findings indicate that mutations in platelet-derived growth factor receptor alpha (PDGFRA) and stem cell growth factor receptor (KIT) exon 11 duplication mutations are associated with a favorable prognosis. Subgroup analyses of randomized trials provide first evidence on how genotyping predicts clinical benefit in the adjuvant setting. In the palliative setting, genotyping should be performed for dose selection but may also be relevant in patients who are intolerant to imatinib. For patients whose tumors harbor the notoriously resistant D842V PDGFRA mutations, novel inhibitors have entered clinical trials, which may end the therapeutic deadlock. Several novel targets have been identified that are currently being investigated in GIST, including inhibitors against fibroblast growth factor receptor, hepatocyte growth factor receptor, mitogen-activated protein, and phosphoinositide 3-kinase. Preliminary clinical data suggest that predictive markers will be needed to define sensitive molecular subgroups.

Summary
Genotyping should be an integral part of clinical management of GIST as it aids in prognostication, prediction of efficacy, and selection of drugs and dosing. Genotyping reduces the risk of both unnecessary adjuvant treatment as well as undertreatment and overtreatment in the palliative setting.
Latent Profiles of Externalizing Psychopathology and Their Relation to Children's Aggression and Social Behavior
Authors: Andrade Brendan F. , Wade Mark 
Published: May 2016

ABSTRACT:

Objective:
This study identified profiles of clinic-referred children with disruptive behavior and determined the association between identified profiles and children's aggression, peer problems, and prosocial skills.

Method:
Parents and teachers of 208 children (163 boys) aged 6 to 12 years (M
age = 8.80, SD = 1.75) completed measures to assess children's callous-unemotional (CU) traits, inattentive-impulsive-overactive (IO) and oppositional-defiant (OD) behavior, aggression, and social behaviors. Latent class analysis was used to identify the profiles, and the pseudoclass draw method to test the equality of means for each of the aggression and social behavioral outcomes across the latent classes.

Results:
Five profiles were identified: (1) Low (35.6% of children), with relatively low levels of CU traits and IO and OD behavior; (2) Low-Moderate (30.8%), with low-moderate levels of CU traits, low IO and moderate OD behavior; (3) Moderate (21.6%), with moderate levels of CU traits and IO and moderate-high OD behavior; (4) Moderate-High (7.2%), with moderate-high levels of CU traits, high IO and moderate-high OD behavior; and (5) High (4.8%), with high levels of CU traits, IO and OD behavior.

Conclusion:
Children categorized into profiles showed important differences in level of aggression and social behavior. The overlap between CU traits, IO, and OD behavior add to understanding of child psychopathology that influences behavior and clinical outcomes.