bluuebunny/crossref_metadata_2025_split huggingface dataset:
Repeated Piperacillin-Tazobactam Plasma Concentration Measurements in Severely Obese Versus Nonobese Critically Ill Septic Patients and the Risk of Under– and Overdosing*
Authors: Jung Boris , Mahul Martin , Breilh Dominique , Legeron Rachel , Signe Jeremy , Jean-Pierre Helene , Uhlemann Anne-Catrin , Molinari Nicolas , Jaber Samir 
Published: February 2017

Objective:
Obesity and critical illness modify pharmacokinetics of antibiotics, but piperacillin-tazobactam continuous IV infusion pharmacokinetics has been poorly studied in obese critically ill patients. We aimed to compare pharmacokinetics of piperacillin in severely obese and nonobese patients with severe sepsis or septic shock. We hypothesized that plasma concentration variability would expose the critically ill to both piperacillin under and overdosing.

Methods:
Prospective comparative study. Consecutive critically ill severely obese (body mass index, > 35 kg/m2) and nonobese patients (body mass index, < 30 kg/m2) were treated with 16 g/2 g/24 hr continuous piperacillin-tazobactam infusion. Piperacillin plasma concentration was measured every 12 hours over a 7-day period by high-pressure liquid chromatography. Unbound piperacillin plasma concentration and fractional time of plasma concentration spent over 64 mg/L (4-fold the minimal inhibitory concentration for Pseudomonas aeruginosa) were compared between the two groups. We performed 5,000 Monte Carlo simulations for various dosing regimens and minimal inhibitory concentration and calculated the probability to spend 100% of the time over 64 mg/L.

Results:
We enrolled 11 severely obese and 12 nonobese patients and obtained 294 blood samples. We did not observe a statistically significant difference in piperacillin plasma concentrations over time between groups. The fractional time over 64 mg/L was 64% (43–82%) and 93% (85–100%) in obese and nonobese patients, respectively, p = 0.027 with intra- and intergroup variability. Five nonobese and two obese patients experienced potentially toxic piperacillin plasma concentrations. When 64 mg/L was targeted, Monte Carlo simulations showed that 12 g/1.5 g/24 hr was inadequate in both groups and 16 g/2 g/24 hr was adequate only in nonobese patients.

Conclusion:
Using a conventional dosing of 16 g/2 g/24 hr continuous infusion, obese patients were more likely than nonobese patients to experience piperacillin underdosing when facing high minimal inhibitory concentration pathogens. The present study suggests that piperacillin drug monitoring might be necessary in the sickest patients who are at the highest risk of unpredictable plasma concentration exposing them to overdose, toxicity, underdosing, and treatment failure.
Can We Identify Parents Who Do Not Verbally Share Concerns for Their Children's Development?
Authors: Eremita Matthew , Semancik Eileen , Lerer Trudy , Dworkin Paul H. 
Published: February 2017

ABSTRACT:

Objective:
We aimed to identify characteristics of parents who do not voice developmental concerns when prompted by their children's nurse and/or primary care provider (PCP), despite reporting concerns on parent-completed questionnaires.

Methods:
We reviewed 376 medical records of children seen for a 9-month well-child visit in an urban pediatric clinic between September 2011 and December 2012 for sociodemographic variables hypothesized to affect parents' sharing of developmental concerns: the child's birth order and gender; parents' education level, employment, relationship status, and primary language; and family size and racial/ethnic background. The target population was parents who reported concerns on the Parents' Evaluation of Developmental Status (PEDS), a routinely administered, parent-completed screening questionnaire. We subdivided parents who reported concerns on the PEDS (N = 86) based on whether they voiced developmental concerns when prompted by their children's nurse and/or PCP. Two-sided Fisher's exact tests and logistic regression evaluated the relationship between sociodemographic variables and parents' voicing of developmental concerns.

Results:
Only parent education approached significance, as parents with less than a high school education (<HS) were more likely to not voice concerns for their children's development than parents with at least a high school degree or equivalent (≥HS) (63% compared to 35%, p = .056). Univariate logistic regression analysis showed that parents with <HS were 3.238 (1.085–9.663, 95% CI, p = .035) times more likely to not verbally share developmental concerns than those with ≥HS.

Conclusion:
Parents with low educational attainment may be more likely to not verbally share their developmental concerns. For children of such parents, early detection of developmental delay may be strengthened by use of written questionnaires.
The Impact of Two Operating Surgeons on Microsurgical Breast Reconstruction
Authors: Weichman Katie E. , Lam Gretl , Wilson Stelios C. , Levine Jamie P. , Allen Robert J. , Karp Nolan S. , Choi Mihye , Thanik Vishal D. 
Published: February 2017

Background:
Given the complexity of microsurgical breast reconstruction, there are many opportunities to improve both surgical efficiency and outcomes. The use of two operating surgeons has been employed, but the outcomes are unproven. In this study, the authors compare the outcomes of patients undergoing microsurgical breast reconstruction with one operating surgeon to those with two surgeons.

Methods:
A retrospective review of all patients undergoing microsurgical breast reconstruction between July of 2011 and January of 2014 at a single academic institution was conducted. Patients were divided into two cohorts: those undergoing reconstruction with one surgeon and those having reconstruction with two surgeons. Once identified, patients were analyzed and outcomes were compared.

Results:
A total of 157 patients underwent 248 microsurgical breast reconstructions during the study period. One hundred three patients (170 flaps) had two surgeons and 54 patients (78 flaps) had one surgeon. Patients undergoing unilateral and bilateral reconstructions with two surgeons had decreased mean operating room time by 60.1 minutes and 134 minutes (p < 0.001) and length of stay by 1.8 days and 1.3 days (p < 0.05), when compared to a single surgeon. Additionally, patients with one surgeon were more likely to have postoperative donor-site breakdown at 5.1 percent (n = 4) versus 0.6 percent (n = 1) (p = 0.0351).

Conclusions:
The use of two operating surgeons has demonstrable effects on the outcomes of microsurgical breast reconstruction. The addition of a second surgeon significantly decreases operating room time and shortens hospital length of stay in both unilateral and bilateral reconstruction. It also significantly decreases donor-site wound healing complications.

CLINICAL QUESTION/LEVEL OF EVIDENCE:
Therapeutic, III.
The Effect of Atorvastatin on the Viability of Ischemic Skin Flaps in Diabetic Rats
Authors: Jia Ya-Chao , Xu Jia , Chen Hong-Hao , Kang Qing-Lin , Chai Yi-Min 
Published: February 2017

Background:
Endothelial progenitor cells play a critical role in neovascularization. However, the mobilization, recruitment, and functional capacity of endothelial progenitor cells are significantly impaired in diabetes. Statins have been shown to augment the number and improve the function of endothelial progenitor cells. This study investigated the effects of statins on the viability of ischemic skin flaps in diabetic rats.

Methods:
Twenty normal and 40 diabetic Sprague-Dawley rats were included in this study. Atorvastatin (10 mg/kg/day) was administered orally in 20 diabetic rats at 2 weeks before flap surgery for 21 consecutive days. Other rats received equal vehicle. Two weeks after first gavage, a 3 × 10-cm skin flap was established on the backs of rats. The necrotic area of each skin flap was measured at 7 days postoperatively. Capillary density and endothelial progenitor cells recruited to the flaps were analyzed using immunofluorescence staining. Circulating endothelial progenitor cell number was determined by flow cytometry. In vitro migration and tube formation experiments were used to analyze the function of endothelial progenitor cells.

Results:
Atorvastatin treatment increased flap survival rate and capillary density. In addition, more endothelial progenitor cells were identified in peripheral blood and skin flaps in diabetic rats receiving atorvastatin. Atorvastatin treatment also restored the impaired function of diabetic endothelial progenitor cells in migration and tube formation.

Conclusion:
Atorvastatin notably promoted neovascularization and enhanced the viability of ischemic skin flaps in diabetic rats, which may be mediated at least partially by augmenting the number and restoring the functional capacity of endothelial progenitor cells.
Evaluating the Efficacy of Monobloc Distraction in the Crouzon-Pfeiffer Craniofacial Deformity Using Geometric Morphometrics
Authors: Visser Richard , Ruff Clifford F. , Angullia Freida , Ponniah Allan J. T. , Jeelani N. U. Owase , Britto Jonathan A. , Koudstaal Maarten J. , Dunaway David J. 
Published: February 2017

Background:
Crouzon-Pfeiffer syndrome is caused by mutations predominantly in the FGFR2 gene leading to syndromic craniosynostosis and midfacial hypoplasia. Monobloc distraction aims to correct both functional and aesthetic disharmony as a result of midfacial hypoplasia. This study evaluates the corrective effects and effectiveness of monobloc distraction in Crouzon-Pfeiffer patients.

Methods:
Preoperative and postoperative scans were collected from 20 Crouzon and two Pfeiffer patients aged 7 to 20 years. Fifty-six normal skulls were used as a control group. Geometric morphometrics using 52 frontofacial landmarks were used to analyze the normal skull and preoperative and postoperative patient skulls. Color maps were created to visualize differences among the average normal, preoperative, and postoperative Crouzon-Pfeiffer patients.

Results:
In the studied patient population, monobloc distraction with the use of an external distractor advanced the upper half of the midface more than the lower half of the midface. There was an anteroinferior rotation in the monobloc segment. The zygomatic arch length improved on average to 88 and 90 percent of normal (right and left, respectively), whereas globe protrusion was corrected from 134 percent to 84 percent and from 131 percent to 87 percent of normal (right and left, respectively) in the studied patient population. Compared with a normal skull, the maxillary region remained retruded.

Conclusions:
The advancement achieved by monobloc distraction is effective in the upper half of the midface; the lower half of the midface is advanced but remains retruded in comparison with the normal population. The midface is rotated anteroinferiorly.

CLINICAL QUESTION/LEVEL OF EVIDENCE:
Therapeutic, IV.
Homeotic and Embryonic Gene Expression in Breast Adipose Tissue and in Adipose Tissues Used as Donor Sites in Plastic Surgery
Authors: Foissac Rémi , Villageois Phi , Chignon-Sicard Bérengère , Georgiou Charalambos , Camuzard Olivier , Dani Christian 
Published: February 2017

Background:
Autologous fat grafting has become an essential procedure in breast reconstructive surgery. However, molecular knowledge of different adipose donor sites remains inadequate. Tissue regeneration studies have shown that it is essential to match the Hox code of transplanted cells and host tissues to achieve correct repair. This study aims to provide a better molecular understanding of adipose tissue.

Methods:
Over the course of 1 year, the authors prospectively included 15 patients and studied seven adipose areas: chin, breast, arm, abdomen, thigh, hip, and knee. The first step consisted of the surgical harvesting of adipose tissue. RNA was then extracted and converted into cDNA to study gene expression levels of 10 targeted genes by real-time polymerase chain reaction.

Results:
Forty samples from Caucasian women with a mean age of 48 years were studied. The expression of PAX3, a marker of neuroectodermal origin, was significantly higher in the breast, with a decreasing gradient from the upper to lower areas of the body. An inverse gradient was found for the expression of HOXC10. This expression profile was statistically significant for the areas of the thigh and knee compared with the breast (p < 0.0083).

Conclusions:
Breast fat may have a specific embryologic origin compared with the knee and thigh. The reinjection of adipocytes from the infraumbilical area leads to the transfer of cells highly expressing HOXC10. This study raises questions about the safety of this procedure, and future studies will be required to examine molecular modifications of adipose cells transferred to a heterotopic location.

CLINICAL QUESTION/LEVEL OF EVIDENCE:
Therapeutic, V.
Laboratory Models for the Study of Normal and Pathologic Wound Healing
Authors: Boyko Tatiana V. , Longaker Michael T. , Yang George P. 
Published: February 2017

Summary:
Current knowledge of wound healing is based on studies using various in vitro and in vivo wound models. In vitro models allow for biological examination of specific cell types involved in wound healing. In vivo models generally provide the full spectrum of biological responses required for wound healing, including inflammation and angiogenesis, and provide cell-cell interactions not seen in vitro. In this review, the authors aim to delineate the most relevant wound healing models currently available and to discuss their strengths and limitations in their approximation of the human wound healing processes to aid scientists in choosing the most appropriate wound healing models for designing, testing, and validating their experiments.
Can I Make Robotic Surgery Make Sense in My Practice?
Authors: Selber Jesse C. 
Published: February 2017

Summary:
Over the past 10 years, robotic technology has had a significant impact on minimally invasive surgery. Because plastic surgery is rooted in “open” techniques, robotic applications in the specialty have been slow to emerge. That said, robotic technology possesses superhuman precision and high-definition, three-dimensional optics that are promising attributes in the hands of the plastic surgeon. In this article, the author explores three applications in robotic plastic surgery: (1) transoral robotic reconstructive surgery for head and neck reconstruction, permitting complex oropharyngeal reconstruction without dividing the lip or mandible; (2) robotic muscle harvest, permitting minimally invasive harvest of the latissimus dorsi and rectus abdominis muscle; and (3) robotic microanastomoses, extending the capabilities of the human hand in microvascular and microlymphatic surgery. An overview of the concepts, surgical techniques, and indications is provided. Although progress has been made, many barriers remain to adopting this technology in its current state, and these are also discussed. Robotic surgery is just beginning to have an impact on the field of plastic surgery. As this technology continues to advance in and out of the operating room, it will play an increasingly prominent role in our specialty and in our lives.
Efficacy and Clinical Utility of a High-Attenuation Object Artifact Reduction Algorithm in Flat-Detector Image Reconstruction Compared With Standard Image Reconstruction
Authors: Naehle Claas P. , Hechelhammer Lukas , Richter Heiko , Ryffel Fabian , Wildermuth Simon , Weber Johannes 
Published: February 2017

Objective
To evaluate the effectiveness and clinical utility of a metal artifact reduction (MAR) image reconstruction algorithm for the reduction of high-attenuation object (HAO)–related image artifacts.

Methods
Images were quantitatively evaluated for image noise (noiseSD and noiserange) and qualitatively for artifact severity, gray–white-matter delineation, and diagnostic confidence with conventional reconstruction and after applying a MAR algorithm.

Results
Metal artifact reduction reduces noiseSD and noiserange (median [interquartile range]) at the level of HAO in 1-cm distance compared with conventional reconstruction (noiseSD: 60.0 [71.4] vs 12.8 [16.1] and noiserange: 262.0 [236.8] vs 72.0 [28.3]; P < 0.0001). Artifact severity (reader 1 [mean ± SD]: 1.1 ± 0.6 vs 2.4 ± 0.5, reader 2: 0.8 ± 0.6 vs 2.0 ± 0.4) at level of HAO and diagnostic confidence (reader 1: 1.6 ± 0.7 vs 2.6 ± 0.5, reader 2: 1.0 ± 0.6 vs 2.3 ± 0.7) significantly improved with MAR (P < 0.0001). Metal artifact reduction did not affect gray–white-matter delineation.

Conclusions
Metal artifact reduction effectively reduces image artifacts caused by HAO and significantly improves diagnostic confidence without worsening gray–white-matter delineation.
Weighted Mean of Signal Intensity for Unbiased Fiber Tracking of Skeletal Muscles
Authors: Giraudo Chiara , Motyka Stanislav , Weber Michael , Resinger Christoph , Thorsten Feiweier , Traxler Hannes , Trattnig Siegfried , Bogner Wolfgang 
Published: February 2017

Objectives
The aim of this study was to investigate the origin of random image artifacts in stimulated echo acquisition mode diffusion tensor imaging (STEAM-DTI), assess the role of averaging, develop an automated artifact postprocessing correction method using weighted mean of signal intensities (WMSIs), and compare it with other correction techniques.

Materials and Methods
Institutional review board approval and written informed consent were obtained. The right calf and thigh of 10 volunteers were scanned on a 3 T magnetic resonance imaging scanner using a STEAM-DTI sequence.
Artifacts (ie, signal loss) in STEAM-based DTI, presumably caused by involuntary muscle contractions, were investigated in volunteers and ex vivo (ie, human cadaver calf and turkey leg using the same DTI parameters as for the volunteers). An automated postprocessing artifact correction method based on the WMSI was developed and compared with previous approaches (ie, iteratively reweighted linear least squares and informed robust estimation of tensors by outlier rejection [iRESTORE]). Diffusion tensor imaging and fiber tracking metrics, using different averages and artifact corrections, were compared for region of interest– and mask-based analyses. One-way repeated measures analysis of variance with Greenhouse-Geisser correction and Bonferroni post hoc tests were used to evaluate differences among all tested conditions. Qualitative assessment (ie, images quality) for native and corrected images was performed using the paired t test.

Results
Randomly localized and shaped artifacts affected all volunteer data sets. Artifact burden during voluntary muscle contractions increased on average from 23.1% to 77.5% but were absent ex vivo. Diffusion tensor imaging metrics (mean diffusivity, fractional anisotropy, radial diffusivity, and axial diffusivity) had a heterogeneous behavior, but in the range reported by literature. Fiber track metrics (number, length, and volume) significantly improved in both calves and thighs after artifact correction in region of interest– and mask-based analyses (P < 0.05 each). Iteratively reweighted linear least squares and iRESTORE showed equivalent results, but WMSI was faster than iRESTORE. Muscle delineation and artifact load significantly improved after correction (P < 0.05 each).

Conclusions
Weighted mean of signal intensity correction significantly improved STEAM-based quantitative DTI analyses and fiber tracking of lower-limb muscles, providing a robust tool for musculoskeletal applications.
Widespread impact of DNA replication on mutational mechanisms in cancer
Authors: Tomkova Marketa , Tomek Jakub , Kriaucionis Skirmantas , Schuster-Böckler Benjamin 
Published: February 2017

ABSTRACTDNA replication plays an important role in mutagenesis, yet little is known about how it interacts with other mutagenic processes. Here, we use somatic mutation signatures – each representing a mutagenic process – derived from 3056 patients spanning 19 cancer types to quantify the asymmetry of mutational signatures around replication origins and between early and late replicating regions. We observe that 22 out of 29 mutational signatures are significantly impacted by DNA replication. The distinct associations of different signatures with replication timing and direction around origins shed new light on several mutagenic processes, for example suggesting that oxidative damage to the nucleotide pool substantially contributes to the mutational landscape of esophageal adenocarcinoma. Together, our results indicate an involvement of DNA replication and associated damage repair in most mutagenic processes.
PHESANT: a tool for performing automated phenome scans in UK Biobank
Authors: Millard Louise A C , Davies Neil M , Gaunt Tom R , Davey Smith George , Tilling Kate 
Published: February 2017

ABSTRACTMotivationEpidemiological cohorts typically contain a diverse set of phenotypes such that automation of phenome scans is non-trivial, because they require highly heterogeneous models. For this reason, phenome scans have to date tended to use a smaller homogeneous set of phenotypes that can be analysed in a consistent fashion. We present PHESANT (PHEnome Scan ANalysis Tool), a software package for performing comprehensive phenome scans in UK Biobank.General featuresPHESANT tests the association of a specified trait with all continuous, integer and categorical variables in UK Biobank, or a specified subset. PHESANT uses a novel rule-based algorithm to determine how to appropriately test each trait, then performs the analyses and produces plots and summary tables.ImplementationThe PHESANT phenome scan is implemented in R. PHESANT includes a novel Javascript D3.js visualization, and accompanying Java code that converts the phenome scan results to the required JavaScript Object Notation (JSON) format.AVAILABILITYPHESANT is available on GitHub at [https://github.com/MRCIEU/PHESANT]. Git tag v0.2 corresponds to the version presented here.
How to name and classify your phage: an informal guide
Authors: Adriaenssens Evelien M. , Brister J. Rodney 
Published: February 2017

AbstractWith this informal guide, we try to assist both new and experienced phage researchers through two important stages that follow phage discovery, i.e. naming and classification. Providing an appropriate name for a bacteriophage is not as trivial as it sounds and the effects might be long-lasting in databases and in official taxon names. Phage classification is the responsibility of the Bacterial and Archaeal Viruses Subcommittee (BAVS) of the International Committee on the Taxonomy of Viruses (ICTV). While the BAVS aims at providing a holistic approach to phage taxonomy, for individual researchers who have isolated and sequenced a new phage, this can be a little overwhelming. We are now providing these researchers with an informal guide to phage naming and classification, taking a “bottom-up” approach from the phage isolate level.
No effect of hippocampal lesions on stimulus-response bindings
Authors: Henson Richard N. , Horner Aidan J. , Greve Andrea , Cooper Elisa , Gregori Mariella , Simons Jon S. , Erzinçioğlu Sharon , Browne Georgina , Kapur Narinder 
Published: February 2017

AbstractThe hippocampus is believed to be important for rapid learning of arbitrary stimulus-response contingencies, or S-R bindings. In support of this, Schnyeret al., 2006 (Experiment 2) measured priming of reaction times (RTs) to categorise visual objects, and found that patients with medial temporal lobe damage, unlike healthy controls, failed to show evidence of reduced priming when response contingencies were reversed between initial and repeated categorisation of objects (a signature of S-R bindings). We ran a similar though extended object classification task on 6 patients who appear to have selective hippocampal lesions, together with 24 age-matched controls. Unlike Schnyeret al., 2006, we found that reversing response contingencies abolished priming in both controls and patients. Bayes Factors provided no reason to believe that response reversal had less effect on patients than controls. We therefore conclude that it is unlikely that the hippocampus is needed for S-R bindings.