bluuebunny/crossref_metadata_2025_split huggingface dataset:
High-frequency oscillatory ventilation: still a role?
Authors: Ng Jensen , Ferguson Niall D. 
Published: February 2017

Purpose of review
In light of emerging data from clinical trials, the place of high-frequency oscillatory ventilation (HFOV) in the management of acute respiratory distress syndrome (ARDS) is uncertain. This review provides an overview of these new clinical data and also explores new areas of investigation for HFOV in adults.

Recent findings
While prior meta-analyses suggested benefit for HFOV, updated systematic reviews published this year, which include two large recent clinical trials, now show no statistically significant impact of HFOV on mortality in adults with ARDS. It is possible that HFOV would be safer and more effective with a more individualized approach to setting mean airway pressure (mPaw). Possible techniques to achieve this include titrating mPaw in response to oxygenation or hemodynamic changes after HFOV initiation, by measuring respiratory system impedance, or by following echocardiographic changes.

Summary
Although not first-line, HFOV remains a tool in the armamentarium of the intensivist managing the patient with severe ARDS and refractory hypoxemia. A refinement in the approach to delivering HFOV is warranted, with more attention paid to its adverse hemodynamic consequences.
Spreading depolarization monitoring in neurocritical care of acute brain injury
Authors: Hartings Jed A. 
Published: February 2017

Purpose of review
Spreading depolarizations are unique in being discrete pathologic entities that are well characterized experimentally and also occur commonly in patients with substantial acute brain injury. Here, we review essential concepts in depolarization monitoring, highlighting its clinical significance, interpretation, and future potential.

Recent findings
Cortical lesion development in diverse animal models is mediated by tissue waves of mass spreading depolarization that cause the toxic loss of ion homeostasis and limit energy substrate supply through associated vasoconstriction. The signatures of such deterioration are observed in electrocorticographic recordings from perilesional cortex of patients with acute stroke or brain trauma. Experimental work suggests that depolarizations are triggered by energy supply–demand mismatch in focal hotspots of the injury penumbra, and depolarizations are usually observed clinically when other monitoring variables are within recommended ranges. These results suggest that depolarizations are a sensitive measure of relative ischemia and ongoing secondary injury, and may serve as a clinical guide for personalized, mechanistically targeted therapy. Both existing and future candidate therapies offer hope to limit depolarization recurrence.

Summary
Electrocorticographic monitoring of spreading depolarizations in patients with acute brain injury provides a sensitive measure of relative energy shortage in focal, vulnerable brains regions and indicates ongoing secondary damage. Depolarization monitoring holds potential for targeted clinical trial design and implementation of precision medicine approaches to acute brain injury therapy.
Lessons learned in applying the International Society for Pharmacoeconomics and Outcomes Research methodology to translating Canadian Emergency Department Information System Presenting Complaints List into German
Authors: Brammen Dominik , Greiner Felix , Dormann Harald , Mach Carsten , Wrede Christian , Ballaschk Anne , Stewart Declan , Walker Steven , Oesterling Christine , Kulla Martin 
Published: February 2017

Objectives
The patient’s presenting complaint guides diagnosis and treatment in the emergency department, but there is no classification system available in German. The Canadian Emergency Department Information System (CEDIS) Presenting Complaint List (PCL) is available only in English and French. As translation risks the altering of meaning, the International Society for Pharmacoeconomics and Outcomes Research (ISPOR) has set guidelines to ensure translational accuracy. The aim of this paper is to describe our experiences of using the ISPOR guidelines to translate the CEDIS PCL into German.

Materials and methods
The CEDIS PCL (version 3.0) was forward-translated and back-translated in accordance with the ISPOR guidelines using bilingual clinicians/translators and an occupationally mixed evaluation group that completed a self-developed questionnaire.

Results
The CEDIS PCL was forward-translated (four emergency physicians) and back-translated (three mixed translators). Back-translation uncovered eight PCL items requiring amendment. In total, 156 comments were received from 32 evaluators, six of which resulted in amendments.

Conclusion
The ISPOR guidelines facilitated adaptation of a PCL into German, but the process required time, language skills and clinical knowledge. The current methodology may be applicable to translating the CEDIS PCL into other languages, with the aim of developing a harmonized, multilingual PCL.
Complexity of mechanisms among human proprotein convertase subtilisin–kexin type 9 variants
Authors: Dron Jacqueline S. , Hegele Robert A. 
Published: February 2017

Purpose of review
There are many reports of human variants in proprotein convertase subtilisin–kexin type 9 (PCSK9) that are either gain-of-function (GOF) or loss-of-function (LOF), with downstream effects on LDL cholesterol and cardiovascular disease (CVD) risk. However, data on particular mechanisms have only been minimally curated.

Recent findings
GOF variants are individually ultrarare, affect all domains of the protein, act to reduce LDL receptor expression through several mechanisms, are a minor cause of familial hypercholesterolemia, have been reported mainly within families, have variable LDL cholesterol–raising effects, and are associated with increased CVD risk mainly through observational studies in families and small cohorts. In contrast, LOF variants can be either ultrarare mutations or relatively more common polymorphisms seen in populations, affect all domains of the protein, act to increase LDL receptor expression through several mechanisms, have variable LDL cholesterol–lowering effects, and have been associated with decreased CVD risk mainly through Mendelian randomization studies in epidemiologic populations.

Summary
There is considerable complexity underlying the clinical concept of both LOF and GOF variants of PCSK9. But despite the underlying mechanistic heterogeneity, altered PCSK9 secretion or function is ultimately correlated with plasma LDL cholesterol level, which is also the driver of CVD outcomes.
Low-density lipoprotein receptor mutational analysis in diagnosis of familial hypercholesterolemia
Authors: Bourbon Mafalda , Alves Ana C. , Sijbrands Eric J. 
Published: February 2017

Purpose of reviewTo present up to date evidence on the pathogenicity of low-density lipoprotein receptor (LDLR) variants and to propose a strategy that is suitable for implementation in the clinical work-up of familial hypercholesterolaemia.Recent findingsMore than 1800 variants have been described in theLDLRgene of patients with a clinical diagnosis of familial hypercholesterolaemia; however, less than 15% have functional evidence of pathogenicity.SummaryThe spectrum of variants in theLDLRidentified in patients with clinical familial hypercholesterolaemia is increasing as novel variants are still being reported. However, over 50% of allLDLRvariants need further evidence before they can be confirmed as mutations causing disease. Even with applying the recent American College of Medical Genetics variant classification, a large number of variants are still considered variants of unknown significance. Before obtaining an undisputable confirmation of the effect on the expression and activity of the LDLR, reporting these variants as part of a clinical diagnosis to the patient holds the risk that it might need to be withdrawn in a later stage. An investment should be made to develop functional assays to characterizeLDLRvariants of unknown significance for a better patient diagnosis and to prevent confusion in the physician's office.
Supratracheal partial laryngectomy: indications, oncologic and functional results
Authors: Succo Giovanni , Fantini Marco , Rizzotto Giuseppe 
Published: February 2017

Purpose of reviewTo describe current evidence about supratracheal laryngectomies, focusing on indications, contraindications, oncologic results, functional outcomes and side-effects of this ‘extreme’ function-sparing surgical approach to laryngeal cancer.Recent findingsIn the latest years, some studies have analyzed oncologic and functional results of open partial supratracheal laryngectomy, a surgical approach whose modern technique was recently described. In selected patients, supratracheal partial laryngectomies show promising long-term oncologic and functional outcomes, similar to those of supracricoid partial laryngectomies.SummaryThe application of supratracheal laryngectomy in the context of a surgical modular approach can be considered a valid and effective therapeutic choice for selected patients with glottic or transglottic laryngeal cancer with subglottic extension, not only in terms of oncologic results, but also in regard of functional outcomes.
Hypoparathyroidism after thyroidectomy: prevention, assessment and management
Authors: Dedivitis Rogerio A. , Aires Felipe T. , Cernea Claudio R. 
Published: February 2017

Purpose of review
Permanent hypoparathyroidism is the most common long-term complication after total thyroidectomy and it can cause significant morbidity and increased costs. Its incidence varies from 30% to 60%.

Recent findings
The surgical technique and the extent of thyroidectomy are related to parathyroid injury and hypoparathyroidism. The glands should be identified in situ, carefully manipulated and preserved, as well as their vascularization. In case of incidental removal, routine autotransplantation is advocated. Low calcium levels, identification of fewer than two parathyroid glands at surgery, reoperation for bleeding, Graves disease and heavier thyroid specimens were considered independent predictors of permanent hypocalcemia. Intraoperative parathyroid hormone (PTH) measurements allows the early detection of hypocalcemia. Treatment is recommended for patients with symptoms of hypocalcemia or corrected serum calcium < 7.5 mg/dL. Acute hypocalcemia is treated with either oral calcium or an intravenous infusion. The goal is to preserve serum calcium in the low normal or mildly subnormal levels. Hypocalcemia symptoms should be considered a medical emergency. Treatment with PTH has been recently performed for the management of cases not adequately controlled with conventional therapy.

Summary
Hypoparathyroidism is the most common long-term complication after total thyroidectomy. Adequate recognition and management decrease its morbidity and costs.
Unique Inflammatory Bowel Disease Phenotype of Pediatric Primary Sclerosing Cholangitis
Authors: Shiau Henry , Ihekweazu Faith D. , Amin Mansi , Fofanova Tatiana , Miloh Tamir , Kellermayer Richard 
Published: February 2017

ABSTRACTObjectives:In adults, primary sclerosing cholangitis (PSC), a cholestatic liver disease characterized by inflammation/fibrosis of intra/extrahepatic bile ducts, associates with a milder form of inflammatory bowel disease (IBD), particularly ulcerative colitis (UC). The pediatric PSC‐IBD phenotype is less well characterized.Methods:We performed a retrospective, single‐center study examining patients with PSC‐IBD at Texas Children's Hospital between 2000 and 2015. IBD‐phenotype (Modified Montreal Classification), medications, laboratory values, endoscopic records, and IBD‐based hospital admissions were collected. PSC‐UC phenotype was compared to UC, non‐PSC patients (n = 95) from Texas Children's Hospital. Elevated gamma‐glutamyl transpeptidase levels were compared to calprotectin levels and IBD‐flare activity, that is, gastrointestinal symptoms resulting in office/emergency department visits or hospital admission.Results:Of 39 patients with PSC‐IBD, 34 (87.2%) had UC (PSC‐UC) and 5 (12.8%) had Crohn disease. Pancolitis was more common in PSC‐UC than UC, non‐PSC (96.3%, 64%, P = 0.0009). Patients with PSC‐UC required less treatment with steroids (76.5%, 91.6%, P = 0.0326) or infliximab (8.8%, 37.9%, P = 0.0011), and fewer had at least 1 IBD‐related hospital admission (32.4%, 63.2%, P = 0.0025) than UC, non‐PSC. Progression to colectomy was significantly less (5.8%, 24.2%, P = 0.0223) in PSC‐UC. Median diagnosis‐to‐colectomy time tended to be longer in PSC‐UC (6.37, 2.5 years, P = 0.0792). In 2 smaller subsets, gamma‐glutamyl transpeptidase did not correlate with calprotectin in PSC‐UC (n = 11, P = 0.7922) and less strongly associated with IBD‐flares in PSC‐UC than UC, non‐PSC (n = 33, n = 67; 15.2%, 41.8%, P = 0.0120).Conclusions:Pediatric PSC appears to associate with milder pancolitic‐UC. PSC and IBD activity do not appear to correlate. Our findings may provide useful information toward etiology and management of pediatric PSC‐IBD.
Risk of Colectomy in Patients With Pediatric‐onset Ulcerative Colitis
Authors: Rinawi Firas , Assa Amit , Eliakim Rami , Mozer‐Glassberg Yael , Nachmias‐Friedler Vered , Niv Yaron , Rosenbach Yoram , Silbermintz Ari , Zevit Noam , Shamir Raanan 
Published: February 2017

ABSTRACTObjectives:Data describing the incidence and risk factors for colectomy in pediatric ulcerative colitis (UC) is inconsistent. Our aim was to describe the colectomy rate and to identify risk factors associated with colectomy in a large cohort of children with UC with long‐term follow‐up.Materials and Methods:We performed a retrospective chart review of pediatric UC cases that were diagnosed at Schneider Children's Medical Center of Israel between 1981 and 2013. Potential predictors for colectomy including age at diagnosis, sex, disease extent, severity indices, and different therapeutic regimens during disease course were assessed.Results:Of 188 patients with pediatric onset UC, 34 (18%) underwent colectomy. Median follow‐up was 6.9 years (range, 1–30). Kaplan‐Meier survival estimates of the cumulative probability for colectomy were 4% at 1 year and 17% at 10 years from diagnosis. Multivariate Cox models showed that male sex (hazard ratio 4.2, P = 0.001) and severe disease at diagnosis reflected by Pediatric Ulcerative Colitis Activity Index score ≥65 (hazard ratio 8.9, P < 0.001) were associated with increased risk for colectomy. Age, disease extent, ethnicity, family history of inflammatory bowel disease, early introduction of immunomodulators, or treatment with antitumor necrosis factor α agent did not affect the risk of colectomy.Conclusions:Male sex and higher Pediatric Ulcerative Colitis Activity Index score at diagnosis are independent risk factors for colectomy.
Diagnosis and Management of Abdominal Wall Endometriosis: A Systematic Review and Clinical Recommendations
Authors: Rindos Noah B. , Mansuria Suketu 
Published: February 2017

Importance
Abdominal wall endometriosis (AWE) is a rare but easily treated cause of pain in women, especially those who have undergone cesarean deliveries.

Objective
This article reviews the diagnosis and management of AWE, a condition that generally develops after surgery but may arise spontaneously. We present a systematic review of the existing literature on AWE, as well as our clinical recommendations for medical and surgical management.

Evidence Acquisition
We searched PubMed and other databases using the search criteria “abdominal wall endometriosis,” “abdominal wall endometriomas,” and “abdominal wall mass.” The references of those articles were then reviewed, and additional publications were evaluated.

Results
Many case reports and case series have been published describing AWE. The overall quality of evidence is poor due to the lack of prospective studies and heterogeneous descriptions of AWE lesions and treatment options. Based on the available literature, it appears that AWE may arise spontaneously but is generally associated with prior pelvic surgery. Abdominal wall endometriosis can be diagnosed with a careful history and physical examination. Imaging including ultrasound and magnetic resonance imaging can assist with localization of the lesions, and aid in surgical excision and management. Lesions that have been removed in their entirety are unlikely to reoccur.

Conclusions and Relevance
Although limited, the body of literature describing management of AWE suggests that it can be successfully treated in most patients with careful surgical planning.

Target Audience
Obstetricians and gynecologists, family physicians.

Learning Objectives
After completing this activity, the learner should be better able to identify risk factors for abdominal wall endometriosis, counsel their patients on management options, and understand the utility of preoperative imaging.
Mucin Balls Influence Corneal Infiltrative Events
Authors: Szczotka-Flynn Loretta B. , Jiang Ying , Stiegemeier Mary Jo , Mutti Donald O. , Walline Jeffrey , Wilson Tawnya , Debanne Sara 
Published: February 2017

ABSTRACT

Purpose
To determine whether mucin ball (MB) formation is protective against corneal infiltrative events (CIEs) as previously reported.

Methods
Two hundred eighty-two eligible participants were enrolled at three sites in the USA. Participants began a 1-month continuous wear run-in period with high modulus lotrafilcon A lenses to assess their ability to form MBs (phase 1). Subsequently, they were stratified by this characteristic and randomized to balafilcon A or comfilcon A lenses for 7-day extended wear and followed for 1 year (phase 2). MB formation in each phase was defined as repeated presence of any MBs on a person level. Multivariable Cox proportional hazards regression was used to model the probability of a CIE as a function of MB formation in each phase and other covariates.

Results
Of the 282 participants who entered phase 1, 218 of them entered the phase 2 randomized trial during which 33 CIEs occurred. Overall, 74%, 61%, and 79% of participants repeatedly produced MBs in lotrafilcon A, balafilcon A, and comfilcon A lenses, respectively. Early repeated MB presence in phase 1 with lotrafilcon A lenses significantly increased the rate of CIEs in phase 2 (12-month follow-up) by 466% (HR 4.66, 95% confidence interval 1.10–19.79, P = .0372). Repeated, longer-term MB presence during wear of balafilcon A or comfilcon A in phase 2 did not significantly reduce the incidence of CIEs; however, it significantly decreased the rate of CIEs by 62% (hazard ratio (HR) 0.380, 95% confidence interval 0.145–0.998, P = .0494).

Conclusions
The overarching hypothesis that MB formation is protective against CIEs throughout extended wear was not supported. Although a protective effect of longer-term MB presence on rate of CIEs was detected, early-onset MB formation substantially increased the hazard for CIE in subsequent wear with different lens types.
Factors Associated With Mortality in Low-Risk Pediatric Critical Care Patients in The Netherlands*
Authors: Verlaat Carin W. , Visser Idse H. , Wubben Nina , Hazelzet Jan A. , Lemson Joris , van Waardenburg Dick , van der Heide Douwe , van Dam Nicolette A. , Jansen Nicolaas J. , van Heerde Mark , van der Starre Cynthia , van Asperen Roelie , Kneyber Martin , van Woensel Job B. , van den Boogaard Mark , van der Hoeven Johannes 
Published: February 2017

Objective:
To determine differences between survivors and nonsurvivors and factors associated with mortality in pediatric intensive care patients with low risk of mortality.

Design:
Retrospective cohort study.

Setting:
Patients were selected from a national database including all admissions to the PICUs in The Netherlands between 2006 and 2012.

Patients:
Patients less than 18 years old admitted to the PICU with a predicted mortality risk lower than 1% according to either the recalibrated Pediatric Risk of Mortality or the Pediatric Index of Mortality 2 were included.

Interventions:
None.

Measurements and Main Results:
In total, 16,874 low-risk admissions were included of which 86 patients (0.5%) died. Nonsurvivors had more unplanned admissions (74.4% vs 38.5%; p < 0.001), had more complex chronic conditions (76.7% vs 58.8%; p = 0.001), were more often mechanically ventilated (88.1% vs 34.9%; p < 0.001), and had a longer length of stay (median, 11 [interquartile range, 5–32] d vs median, 3 [interquartile range, 2–5] d; p < 0.001) when compared with survivors. Factors significantly associated with mortality were complex chronic conditions (odds ratio, 3.29; 95% CI, 1.97–5.50), unplanned admissions (odds ratio, 5.78; 95% CI, 3.40–9.81), and admissions in spring/summer (odds ratio, 1.67; 95% CI, 1.08–2.58).

Conclusions:
Nonsurvivors in the PICU with a low predicted mortality risk have recognizable risk factors including complex chronic condition and unplanned admissions.
Utility of Assessing Cytokine Levels for the Differential Diagnosis of Pneumonia in a Pediatric Population*
Authors: Zhou Jian-Ming , Ye Qing 
Published: February 2017

Objectives:
Although pneumonia is easily diagnosed, determining the causative agent is difficult due to low pathogen detection rates. We performed a prospective observational study to evaluate the utility of measuring inflammatory cytokine levels to discriminate between pneumonia caused by typical bacteria, respiratory syncytial virus, or Mycoplasma pneumoniae in a pediatric population.

Design:
Serum inflammatory cytokine levels at early stages of the disease were evaluated for pneumonia caused by the three different pathogenic microorganisms.

Setting:
The Children’s Hospital of Zhejiang University School of Medicine, China.

Patients:
One hundred sixty-six patients with bacterial pneumonia, 182 with M. pneumonia, and 167 with respiratory syncytial virus pneumonia.

Measurements and Main Results:
The levels of interleukin-6 for pneumonia were significantly higher with typical bacteria than with either Mycoplasma pneumoniae or respiratory syncytial virus (p < 0.001). The area under the curve for serum concentrations of interleukin-6 was 0.997. A serum interleukin-6 level of greater than or equal to 93.0 pg/mL had 100.0% sensitivity and 99.14% specificity in discriminating bacterial pneumonia from respiratory syncytial virus pneumonia and Mycoplasma pneumoniae pneumonia. The interleukin-6 levels were higher in patients with Mycoplasma pneumoniae pneumonia than in those with respiratory syncytial virus pneumonia (p < 0.001). They also simultaneously had lower interleukin-10 levels than patients with respiratory syncytial virus pneumonia who had interleukin-10 levels comparable to those of patients with bacterial pneumonia, indicating a significant difference in the interleukin-6/interleukin-10 ratio between patients with Mycoplasma pneumoniae pneumonia and respiratory syncytial virus pneumonia (median interleukin-6/interleukin-10 ratio, 2.5 vs 0.5; p < 0.001). At an optimal cut-off value of 0.8, the interleukin-6/interleukin-10 ratio showed 90.3% sensitivity and 88.0% specificity.

Conclusions:
These results suggest that interleukin-6 is a good biomarker for identifying bacterial pneumonia and that the interleukin-6/interleukin-10 ratio is an effective biomarker for discriminating Mycoplasma pneumoniae pneumonia from respiratory syncytial virus pneumonia.