bluuebunny/crossref_metadata_2025_split huggingface dataset:
Intersection of prognosis and palliation in neurocritical care
Authors: Rubin Michael , Bonomo Jordan , Hemphill J. Claude 
Published: February 2017

Purpose of review
Difficult discussions regarding end-of-life care are common in neurocritical care. Because of a patient's neurological impairment, decisions regarding continuing or limiting aggressive care must often be made by patients’ families in conjunction with medical providers. This review provides perspective on three major aspects of this circumstance: prognostication, family–physician discussions, and determination of death (specifically as it impacts on organ donation).

Recent findings
Numerous studies have now demonstrated that prediction models developed from populations of brain-injured patients may be misleading when applied to individual patients. Early care limitations may lead to the self-fulfilling prophecy of poor outcomes because of care decisions rather than disease course. A shared decision-making approach that emphasizes transmission of information and trust between families and medical providers is ethically appropriate in severely brain-injured patients and as part of the transition to end-of-life palliative care. Standard definitions of death by neurological criteria exist, although worldwide variation and the relationship to organ donation make this complex.

Summary
End-of-life care in patients with severe brain injuries is common and represents a complex intersection of prognostication, family communication, and decision-making. Skills to optimize this should be emphasized in neurocritical care providers.
Influences on emergency department length of stay for older people
Authors: Street Maryann , Mohebbi Mohammadreza , Berry Debra , Cross Anthony , Considine Julie 
Published: February 2017

Objective
The aim of this study was to examine the influences on emergency department (ED) length of stay (LOS) for older people and develop a predictive model for an ED LOS more than 4 h.

Methods
This retrospective cohort study used organizational data linkage at the patient level from a major Australian health service. The study population was aged 65 years or older, attending an ED during the 2013/2014 financial year. We developed and internally validated a clinical prediction rule. Discriminatory performance of the model was evaluated by receiver operating characteristic (ROC) curve analysis. An integer-based risk score was developed using multivariate logistic regression. The risk score was evaluated using ROC analysis.

Results
There were 33 926 ED attendances: 57.5% (n=19 517) had an ED LOS more than 4 h. The area under ROC for age, usual accommodation, triage category, arrival by ambulance, arrival overnight, imaging, laboratory investigations, overcrowding, time to be seen by doctor, ED visits with admission and access block relating to ED LOS more than 4 h was 0.796, indicating good performance. In the validation set, area under ROC was 0.80, Hosmer–Lemeshow
P-value was 0.36 and prediction mean square error was 0.18, indicating good calibration. The risk score value attributed to each risk factor ranged from 2 to 68 points. The clinical prediction rule stratified patients into five levels of risk on the basis of the total risk score.

Conclusion
Objective identification of older people at intermediate and high risk of an ED LOS more than 4 h early in ED care enables targeted approaches to streamline the patient journey, decrease ED LOS and optimize emergency care for older people.
Genotype-guided diagnosis in familial hypercholesterolemia: clinical management and concerns
Authors: Hopkins Paul N. , Lane Stacey R. 
Published: February 2017

Purpose of review
In this review, we examine benefits and concerns associated with genetic testing in the clinical management of familial hypercholesterolemia (FH).

Recent findings
Application of next-generation sequencing and other advances provide improved yield of causal mutations compared with older methods and help disclose underlying pathophysiology in many instances. Concerns regarding clinical application of genetic testing remain.

Summary
More widespread application of genetic testing for FH in the USA may be forthcoming. When a genetic cause of FH can be identified or is known for the family, test results can provide more accurate individual diagnosis of FH, clarification of underlying pathophysiology, and greater clinical insight. However, several concerns persist, particularly cost to FH patients, potential discrimination, and inappropriate denial of clinically indicated therapies for patients without definitive genetic testing results.
The role of registries and genetic databases in familial hypercholesterolemia
Authors: Kindt Iris , Mata Pedro , Knowles Joshua W. 
Published: February 2017

Purpose of review
To review how leveraging familial hypercholesterolemia registries can impact molecular genetic research and precision medicine.

Recent findings
Familial hypercholesterolemia is both much more common and more phenotypically heterogeneous than previously thought with some evidence for significant genotype to phenotype correlations. Genetic testing for familial hypercholesterolemia is becoming both more widely available and cheaper, spurring conversations about its clinical utility.

Summary
In most countries, familial hypercholesterolemia is underdiagnosed and diagnosed later in life, often after the onset of coronary heart disease (CHD). Familial hypercholesterolemia is undertreated; low goal attainment and additional modifiable risk factors further increase CHD risk. Familial hypercholesterolemia epitomizes the goal of precision medicine to define a subset of individuals with a high risk of morbidity and mortality through genetic diagnosis to manage and treat the risk accordingly. Genetic cascade screening can be used to identify familial hypercholesterolemia patients at a younger age and start timely treatment to prevent CHD. Familial hypercholesterolemia registries are tools for clinical research and improving healthcare planning and patient care. As genotype and phenotype correlations in familial hypercholesterolemia become increasingly understood, this information will likely play a more important role in diagnosis and treatment especially as the cost of genetic testing continues to decline.
Is p16 an adequate surrogate for human papillomavirus status determination?
Authors: Jouhi Lauri , Hagström Jaana , Atula Timo , Mäkitie Antti 
Published: February 2017

Purpose of reviewIn head and neck cancer management, immunoexpression of protein p16 is widely used as a surrogate marker for human papillomavirus (HPV) positivity due to challenges of direct HPV testing. Previously p16 has been reported to have good sensitivity but only moderate specificity in HPV-status determination. The aim of this review is to evaluate the existing information on sensitivity and specificity of p16 immunohistochemistry (IHC) in HPV-status determination among the recent studies.Recent findingsWe searched the time period from October 2014 to April 2016 and included 28 studies (a total of 31 analyses), which reported both p16 and HPV status in their series. The sensitivity of p16 in HPV determination ranged between 28.2 and 100.0%. The mean and median sensitivities were 90.5 and 95.4%, respectively. The specificity ranged between 31.1 and 100.0%. The mean and median specificities were 83.3 and 87.3%, respectively.SummaryOur review presents current information on the feasibility of p16 IHC in HPV status determination, which is in line with previous studies. Patients with HPV-positive tumors can be identified with p16 IHC, but a risk for misclassification of HPV-negative tumors as HPV positive exists. This fact has to be taken into consideration if HPV status will influence treatment planning.
Ex utero intrapartum treatment (EXIT) for upper airway obstruction
Authors: Butler Colin R. , Maughan Elizabeth F. , Pandya Pranav , Hewitt Richard 
Published: February 2017

Purpose of review
Improvements in the antenatal diagnosis of congenital malformations have led to increased detection of fetal airway obstructing lesions, and pediatric ear, nose, and throat surgeons are increasingly involved in these cases.

Recent findings
This article outlines the typical range of pathology seen, the logistics in providing support for anticipated deliveries and the multidisciplinary management of complex airway cases.

Summary
Traditionally, difficulty in obtaining a patent airway at delivery was a major factor in the dismal prognosis of these pregnancies. The ex utero intrapartum treatment procedure, which involves controlled partial delivery of the fetus whilst maintaining placental circulation, allows various airway maneuvers to be performed to secure the airway in a controlled fashion.
Fecal Calprotectin in Cystic Fibrosis and Its Relation to Disease Parameters
Authors: Ellemunter Helmut , Engelhardt Alexander , Schüller Katharina , Steinkamp Gratiana 
Published: February 2017

ABSTRACTObjectives:Fecal calprotectin (FC) is a marker of inflammation in the intestinal tract. We assessed FC levels longitudinally in patients with cystic fibrosis (CF) and evaluated the relation between FC results and relevant markers of disease.Methods:Calprotectin was measured in fecal samples starting in 2003 and values were stored in the center's patient database. In this retrospective analysis, we searched for associations of FC concentrations with disease severity and progression. Linear mixed effects models were used to model the logarithm of FC levels.Results:A total of 171 patients (0–61 years) had 2434 FC measurements between 2003 and 2015, with a total observation period of 1686 patient‐years. Median (interquartile range) FC concentrations were 60.9 (75.9) μg/g and 61% of the samples showed elevated FC concentrations (>50 μg/g). Despite some statistically significant effects, there was no clinically relevant association among FC and sex, age, forced expiratory volume in 1 second z score, or body mass index z score. Pancreatic insufficiency (ie, fecal elastase <100 μg/g stool) was associated with considerably higher FC values compared to normal pancreatic function (median FC 68 vs 29 μg/g, P < 0.0001). F508del homozygous subjects showed a trend to higher FC values than heterozygous patients (median 71 vs 62 μg/g, P = 0.173). In addition, a significant association with increasing serum C‐reactive protein concentrations (P < 0.0001) was observed.Conclusions:FC was elevated in two‐thirds of stool specimens. Increased FC was more common in patients with pancreatic insufficiency. Whether increased FC reflects intestinal inflammation in patients with CF remains to be determined.
Risk Factors for Birth Defects
Authors: Harris Benjamin S. , Bishop Katherine C. , Kemeny Hanna R. , Walker Jennifer S. , Rhee Eleanor , Kuller Jeffrey A. 
Published: February 2017

Importance
Major congenital abnormalities, or birth defects, carry significant medical, surgical, cosmetic, or lifestyle consequences. Such abnormalities may be syndromic, involving multiple organ systems, or can be isolated. Overall, 2% to 4% of live births involve congenital abnormalities. Risk factors for birth defects are categorized as modifiable and nonmodifiable. Modifiable risk factors require thorough patient education/counseling. The strongest risk factors, such as age, family history, and a previously affected child, are usually nonmodifiable.

Objective
This review focuses on risk factors for birth defects including alcohol consumption, illicit drug use, smoking, obesity, pregestational diabetes, maternal phenylketonuria, multiple gestation, advanced maternal age, advanced paternal age, family history/consanguinity, folic acid deficiency, medication exposure, and radiation exposure.

Evidence Acquisition
Literature review via PubMed.

Results
There is a strong link between alcohol use, folic acid deficiency, obesity, uncontrolled maternal diabetes mellitus, uncontrolled maternal phenylketonuria, and monozygotic twins and an increased risk of congenital anomalies. Advanced maternal age confers an increased risk of aneuploidy, as well as nonchromosomal abnormalities. Some medications, including angiotensin converting enzyme inhibitors, retinoic acid, folic acid antagonists, and certain anticonvulsants, are associated with various birth defects. However, there are few proven links between illicit drug use, smoking, advanced paternal age, radiation exposure, and statins with specific birth defects.

Conclusions and Relevance
Birth defects are associated with multiple modifiable and nonmodifiable risk factors. Obstetrics providers should work with patients to minimize their risk of birth defects if modifiable risk factors are present and to appropriately counsel patients when nonmodifiable risk factors are present.

Target Audience
Obstetrician and gynecologists, family physicians, maternal-fetal medicine physicians, and genetic counselors.

Learning Objectives
The learner should be better able to (1) outline the most common modifiable maternal risk factors that are associated with birth defects; (2) locate high-quality health information resources for patients; and (3) promote patient autonomy, responsibility, and motivation to pursue healthy lifestyle choices during pregnancy.
Combining Smoothened Agonist and NEL-Like Protein-1 Enhances Bone Healing
Authors: Lee Soonchul , Wang Chenchao , Pan Hsin Chuan , Shrestha Swati , Meyers Carolyn , Ding Catherine , Shen Jia , Chen Eric , Lee Min , Soo Chia , Ting Kang , James Aaron W. 
Published: February 2017

Background:
Nonhealing bone defects represent an immense biomedical burden. Despite recent advances in protein-based bone regeneration, safety concerns over bone morphogenetic protein-2 have prompted the search for alternative factors. Previously, the authors examined the additive/synergistic effects of hedgehog and Nel-like protein-1 (NELL-1) on the osteogenic differentiation of mesenchymal stem cells in vitro. In this study, the authors sought to leverage their previous findings by applying the combination of Smoothened agonist (SAG), hedgehog signal activator, and NELL-1 to an in vivo critical-size bone defect model.

Methods:
A 4-mm parietal bone defect was created in mixed-gender CD-1 mice. Treatment groups included control (n = 6), SAG (n = 7), NELL-1 (n = 7), and SAG plus NELL-1 (n = 7). A custom fabricated poly(lactic-co-glycolic acid) disk with hydroxyapatite coating was used as an osteoinductive scaffold.

Results:
Results at 4 and 8 weeks showed increased bone formation by micro–computed tomographic analyses with either stimulus alone (SAG or NELL-1), but significantly greater bone formation with both components combined (SAG plus NELL-1). This included greater bone healing scores and increased bone volume and bone thickness. Histologic analyses confirmed a significant increase in new bone formation with the combination therapy SAG plus NELL-1, accompanied by increased defect vascularization.

Conclusions:
In summary, the authors’ results suggest that combining the hedgehog signaling agonist SAG and NELL-1 has potential as a novel therapeutic strategy for the healing of critical-size bone defects. Future directions will include optimization of dosage and delivery strategy for an SAG and NELL-1 combination product.
CD1d-Restricted Natural Killer T Cells Are Preserved in Indian Long-Term Nonprogressors
Authors: Singh Dharmendra , Ghate Manisha , Godbole Sheela , Kulkarni Smita , Thakar Madhuri 
Published: February 2017

Background:
Natural killer T (NKT) cells act as a bridge between innate and adaptive immune responses. Limited information is available regarding the role of NKT cells in the HIV disease progression especially HIV-1 C infection.

Methodology:
NKT cells were characterized for their frequency and the activation, aging, exhaustion status, and their proliferation ability in 32 long-term nonprogressors (LTNPs), 40 progressors, 18 patients before and after suppressive combination antiretroviral therapy (cART) along with 35 HIV-1–negative subjects using multicolor flow cytometry.

Results:
The frequencies of total NKT cells and their subpopulation were significantly higher in LTNPs as compared with those obtained in progressors (P < 0.0001) and were significantly associated with higher CD4 counts and with lower plasma viral loads. The percentage of activated, aged, and exhausted NKT cells were significantly lower in LTNPs as compared with the progressors and inversely correlated with CD4 count and positively with plasma viral loads. The NKT cells from the LTNPs showed higher proliferation ability. The frequency and proliferation ability of the NKT cells were partially restored after 12 months of suppressive cART but still lower than the levels in LTNPs. The degree of restoration after cART was similar in both CD4+ and CD4− NKT cells.

Conclusion:
The findings demonstrate significant association of preserved NKT cells with the nonprogressive HIV infection and also showed that exhausted NKT cells are associated with disease progression. Further characterization of their functionality and assessment of sustenance in HIV infection will help to understand the HIV pathogenesis and to develop immune therapies.
Imaging Leukocyte Responses in the Kidney
Authors: Finsterbusch Michaela , Kitching A. Richard , Hickey Michael J. 
Published: February 2017

Abstract
The kidney can be negatively affected by a range of innate and adaptive immune responses, resulting in alterations in the functions of the kidney and, in some cases, progression to renal failure. In many of these responses, infiltration of blood-borne leukocytes into the kidney is central to the response. In addition, a large population of mononuclear phagocytes resident in the kidney can modulate these responses. A great deal of research has investigated both the mechanisms of leukocyte recruitment to the kidney and the actions of immune cells resident within the kidney. Because of the dynamic nature of the processes whereby leukocytes enter sites of inflammation, in vivo imaging has been one of the key approaches used for understanding leukocyte recruitment as it occurs throughout the body, and this is also true for kidney. However, imaging this organ and its complicated microvasculature during different forms of renal pathology presents a unique set of challenges. In this review, we examine the approaches used for intravital imaging of the kidney and summarize the insights gained from these studies regarding the mechanisms of leukocyte entry into the kidney during inflammation and the actions of immune cells within this organ.
Cognitive Performance Under Electroconvulsive Therapy (ECT) in ECT-Naive Treatment-Resistant Patients With Major Depressive Disorder
Authors: Ziegelmayer Christoph , Hajak Göran , Bauer Anne , Held Marion , Rupprecht Rainer , Trapp Wolfgang 
Published: February 2017

Objectives
Although electroconvulsive therapy (ECT) is considered a safe and highly effective treatment option for major depressive disorder, there are still some reservations with regard to possible adverse cognitive adverse effects. This is the case despite a large body of evidence showing that these deficits are transient and that there even seems to be a long-term improvement of cognitive functioning level. However, most data concerning cognitive adverse effects stem from studies using mixed samples of treatment-resistant and non–treatment-resistant as well as ECT-naive and non–ECT-naive subjects. Furthermore, neurocognitive measures might partly be sensitive to practice effects and improvements in depressive symptom level.

Methods
We examined neurocognitive performance in a sample of 20 treatment-resistant and ECT-naive subjects using repeatable neurocognitive tests, whereas changes in depressive symptom level were controlled. Cognitive functioning level was assessed before (baseline), 1 week, and 6 months (follow-up 1 and 2) after (12 to) 15 sessions of unilateral ECT treatment.

Results
No adverse cognitive effects were observed in any of the cognitive domains examined. Instead, a significant improvement in verbal working memory performance was found from baseline to follow-up 2. When changes in depressive symptom levels were controlled statistically, this improvement was no longer seen.

Conclusions
Although findings that ECT does not lead to longer lasting cognitive deficits caused by ECT were confirmed, our study adds evidence that previous results of a beneficial effect of ECT on cognition might be questioned.
Switching From Age-Based Stimulus Dosing to Dose Titration Protocols in Electroconvulsive Therapy
Authors: O’Neill-Kerr Alex , Yassin Anhar , Rogers Stephen , Cornish Janie 
Published: February 2017

Objective
The aim of this study was to test the proposition that adoption of a dose titration protocol may be associated with better patient outcomes, at lower treatment dose, and with comparable cumulative dose to that in patients treated using an age-based stimulus dosing protocol.

Methods
This was an analysis of data assembled from archived records and based on cohorts of patients treated respectively on an age-based stimulus dosing protocol and on a dose titration protocol in the National Health Service in England.

Results
We demonstrated a significantly better response in the patient cohort treated with dose titration than with age-based stimulus dosing. Peak doses were less and the total cumulative dose was less in the dose titration group than in the age-based stimulus dosing group.

Conclusions
Our findings are consistent with superior outcomes in patients treated using a dose titration protocol when compared with age-based stimulus dosing in a similar cohort of patients.