bluuebunny/crossref_metadata_2025_split huggingface dataset:
Patents and non-invasive prenatal testing: Is there cause for concern?
Authors: Hawkins Naomi 
Published: January 2020

AbstractIntellectual property rights are key to the translation of discoveries into clinical use in personalised medicine. This article explores the interaction of intellectual property rights, specifically patents, with the field of genomic personalised medicine, through empirical work investigating the role that patents play in the development and delivery of non-invasive prenatal testing (NIPT). Single gene testing (SGT) and NIPT represent examples of two different types of innovation likely to be important in personalised medicine, and which operate differently in terms of how the law is applied in practice. In SGT, on the one hand, previous studies demonstrate that patents have little impact on practice for those developing genetic tests in the public sector in the UK because they are largely ignored. In contrast, however, this qualitative interview study finds that law and law-in-practice in NIPT are much more convergent than found in SGT. Those involved in the development and delivery of NIPT are more aware of patents, and balance the costs and benefits of greater engagement or compliance with patent law, in relation to factors such as freedom to operate, litigation, and licensing, in favour of compliance. Compliance can take different forms; licensing is compliance, as is forbearance from using a patented invention in the absence of a patent licence. This article explores the factors relevant to patent law compliance in NIPT, and further considers the implications for the field of personalised medicine. It argues that, as the prevalent means to promote openness, access, and affordability in biomedicine are founded on the existing legal structures of intellectual property rights, such solutions will only be effective and adopted when these existing legal structures of intellectual property law are recognised and respected in the relevant field. It is therefore essential that such solutions only be deployed with a nuanced understanding of the operation of the law-in-practice.
Serum Inflammatory Markers in Patients With Knee Osteoarthritis
Authors: Giordano Rocco , Petersen Kristian K. , Andersen Hjalte H. , Simonsen Ole , Arendt-Nielsen Lars 
Published: January 2020

Objectives:Osteoarthritis (OA) is known to be a slowly progressive disease that alters all tissue compartments of the joint involved with a characteristic degradation of the cartilage, bone remodeling, and inflammation. One of the prominent symptoms in OA patients is pain, but a few radiologic, inflammatory, or structurally related biomarkers have shown few if any associations with pain. This study aimed to assess serum levels of 92 markers involved in inflammatory pathways in patients with knee osteoarthritis (KOA) and evaluate their possible associations with the clinical pain intensity.Materials and Methods:Serum samples were collected from 127 KOA patients and 39 healthy participants with no knee pain. Each serum sample was analyzed for 92 inflammatory markers using the Proximity Extension Array (PEA) technology. Clinical pain intensity was assessed using a Visual Analog Scale, and patients completed the Knee Injury and Osteoarthritis Outcome Score (KOOS) questionnaire.Results:Fifteen markers were significantly different when comparing KOA patients and healthy participants. Two markers, fibroblast growth factor-21 and Eukaryotic translation initiation factor 4E-binding protein 1 (4E-BP1), correlated positively with pain intensity (R=0.235,P=0.008;R=0.233,P=0.008). Moreover, a linear regression model showed interleukin-6, macrophage colony-stimulating factor 1, fibroblast growth factor-21, and tumor necrosis factor superfamily member 12 (TWEAK) as significant independent parameters for pain intensity.Discussion:The associations between specific cytokines and KOA pain intensities provide new insights into the understanding of the underlying factors driving the pain in OA.
Accuracy for cytological evaluation in the detection of breast cancer among patients with pathologic nipple discharge: a PRISMA-compliant meta-analysis
Authors: Li Xiao-Qian , Xu Feng , Lei Chu-Qi , Li Jie , Jiang Hong-Chuan 
Published: January 2020

AbstractBackground:Nipple discharge cytology is a simple non-invasive method that may provide valuable information for detecting underlying malignancy. Several studies have investigated the diagnostic value of cytology in breast cancer patients with pathological nipple discharge, but the results have been highly variable. Herein we presented a systematic review and meta-analysis of published studies pertaining to the diagnostic capacity of nipple discharge cytology in patients with breast cancer.Methods:A systematic literature search was performed (Medline/PubMed, Embase, Cochrane Library databases, and Google Scholar) to identify studies that investigated the diagnostic capacity of cytology with regard to breast cancer in patients with pathologic nipple discharge. Two independent researchers identified articles that assessed the sensitivity and specificity of cytological evaluation for breast cancer detection in patients with pathologic nipple discharge published between January 2000 and October 2018. Articles were only included in the meta-analysis if they met predetermined criteria. The characteristics of each study and the data they yielded were summarized. Quality assessment of all articles included was performed using the Methodological Index for Non-randomized Studies Criteria (MINORS) and the Quality Assessment of Diagnostic Accuracy Study 2 (QUADAS-2). Heterogeneity was tested via CochranQtest and theI2statistic using Stata 12.0 and Meta-DiSc 1.4 software, and meta-analysis was performed.Results:A total of 286 articles were identified, of which 12 articles including a total of 1476 patients were deemed eligible for inclusion in the meta-analysis. A random-effects model assessing the capacity of nipple discharge cytology to predict breast cancer yielded pooled sensitivity 63% (95% confidence interval [CI]: 53%–72%), specificity 95% (95% CI: 87%–98%), positive likelihood ratio 12.35 (95% CI: 4.87–31.34), and negative likelihood ratio 0.39 (95% CI: 0.30–0.50). The diagnostic odds ratio was 31.88 (95% CI: 11.30–89.98). The area under the summary receiver operating characteristic curve was 0.79 (95% CI: 0.75–0.82).Conclusion:The current meta-analysis suggests that nipple discharge cytology is a useful diagnostic modality for detection of breast cancer in patients with pathological nipple discharge, with moderate sensitivity and high specificity.
Men Receive Three Times More Industry Payments than Women Academic Orthopaedic Surgeons, Even After Controlling for Confounding Variables
Authors: Forrester Lynn Ann , Seo Lauren J. , Gonzalez Leah J. , Zhao Caixia , Friedlander Scott , Chu Alice 
Published: January 2020

Abstract

Background
In 2016, orthopaedic surgeons received nearly USD 300 million from industry, with the top 10% of recipients making more than 95% of the total amount. The degree to which gender may be associated with industry compensation has not been well explored; however, this may be confounded by a number of variables, including academic productivity, experience, and other factors. We wished to explore the variability in payment distribution by gender after controlling for these factors.

Questions/purposes
(1) Do men or women academic orthopaedic surgeons receive more payments from industry? (2) To what degree do any observed differences between the genders persist, even after accounting for identifiable factors, including academic rank, scholarly productivity, regional location of university, subspecialty selection as identified by fellowships completed, and years since completion of residency?

Methods
This study was a cross-sectional retrospective analysis of surgeons practicing in orthopaedic surgery academic departments in the United States. Academic orthopaedic surgery departments were identified using the Fellowship and Residency Electronic Interactive Database. Publicly available data on gender, academic rank, scholarly productivity, regional location of university, fellowships completed, and years since residency graduation were collected from institutional websites. Industry funding data for 2016 were obtained from the Centers for Medicare & Medicaid Services Open Payments Database, and scholarly productivity data through 2017 were collected from Scopus. A total of 2939 academic orthopaedic surgeons, 2620 (89%) men and 319 (11%) women from 126 programs were identified. Men and women surgeons were different in most of the variables collected, and all except region of university were associated with differences in industry payments.

Results
The median payment for men surgeons was greater than that for women (USD 1027 [interquartile range USD 125-USD 9616] versus USD 177 [IQR USD 47-USD 1486]; difference of medians, USD 850; p < 0.001]. After accounting for potentially confounding variables like faculty rank, years since residency, H-index and subspecialty choice, women faculty members still received only 29% of payments received by otherwise comparable men orthopaedists (beta coefficient for gender = 0.29 [95% CI 0.20 to 0.44; p < 0.001]).

Conclusions
Women academic orthopaedic surgeons received only 29% of the industry payments received by men, even after controlling for faculty rank, years since residency, H-index, and subspecialty selection. This gender-related disparity may hinder the career advancement of women orthopaedic surgeons.

Clinical Relevance
Increased transparency by companies can help guide orthopaedic surgeons who wish to receive industry funding.
French Kiss Technique: An Anatomical Study and Description of a New Method for Safe Lip Eversion
Authors: Trévidic Patrick , Criollo-Lamilla Gisella 
Published: January 2020

BACKGROUND
To minimize complications with injectable fillers, aesthetic practitioners need a detailed knowledge of facial anatomy.

OBJECTIVE
To describe a novel approach (“subtractive anatomy”) to identify locations where lip eversion using filler injections would be well tolerated and to evaluate the “French kiss technique” (FKT) to enhance the length of the lips using a low cohesivity hyaluronic acid filler.

MATERIALS AND METHODS
Twenty hemifaces were dissected from 10 nonembalmed, nonfrozen Caucasian cadavers to assess subtractive anatomy. The FKT “proof-of-concept” evaluation enrolled 120 patients (114 women; mean age 42 years).

RESULTS
The arterial supply of the lips shows marked anatomical variations between patients and when comparing sides of the face in the same person. The dissections revealed a “safe area” for filler injections in the submucosal plane 3 to 4 mm above the vermilion–mucosa junction of the upper lip and 3 to 5 mm below the vermilion–mucosa junction of the lower lip. Preliminary results suggest that FKT is associated with very good cosmetic outcomes and no major complications.

CONCLUSION
Based on our anatomical studies and the literature, we developed the novel FKT for the injection of lip fillers, which produced a marked natural lip plumping effect. Further evaluation is underway.
Synergistic effect of the association between lidocaine and magnesium sulfate on peri-operative pain after mastectomy
Authors: Mendonça Fabricio T. , Pellizzaro Douglas , Grossi Breno J. , Calvano Luise A. , de Carvalho Luiz S.F. , Sposito Andrei C. 
Published: January 2020

BACKGROUND
Recently, the use of venous adjuvants, such as lidocaine and magnesium sulfate, has been gaining ground in multimodal analgesia. However, no study has evaluated the impact a combination of the two drugs.

OBJECTIVES
To evaluate the efficacy of venous adjuvants in reducing opioid consumption and pain scores after mastectomy.

DESIGN
Randomised, double-blind, parallel-group, noninferiority clinical trial with a 1 : 1 : 1 : 1 allocation ratio.

SETTING
Hospital de Base do Distrito Federal, Brasilia, Federal District, Brazil from November 2014 to December 2017.

PATIENTS
One-hundred and ninety-eight patients were electively scheduled for mastectomy. Seventy-eight were excluded.

INTERVENTIONS
Intra-operative infusions of remifentanil (0.1 μg kg−1 min−1), lidocaine (3 mg kg−1 h−1), magnesium sulfate (50 mg kg−1 + 15 mg kg−1 h−1) or lidocaine with magnesium sulfate were used. All patients received standard general anaesthesia.

MAIN OUTCOME MEASURES
Peri-operative opioid consumption and pain scores.

RESULTS
The patients who received both lidocaine and magnesium sulfate group (n=30) consumed less alfentanil during surgery (P < 0.001) and less dipyrone (P < 0.001) and morphine (P < 0.001) in the postoperative period. Only two patients (6.7%) in the lidocaine and magnesium sulfate group needed morphine (P < 0.001). These requirements were significantly lower when compared with patients who received remifentanil (n=30; 76.6%) and magnesium sulfate (n=30; 70%; odds ratio 46.0, 95% confidence interval 8.69 to 243.25, P < 0.001, and odds ratio 32.66, 95% confidence interval 6.37 to 167.27, P < 0.001, respectively). The patients of the lidocaine and magnesium sulfate group had lower pain scores in the first 24 h postoperatively using the numerical rating scale and verbal rating scale at discharge from the postanaesthesia care unit (P < 0.001), after 12 h (P < 0.001) and after 24 h (P < 0.001) when compared with the other three groups.

CONCLUSION
Our findings suggest a synergistic effect of the use of both lidocaine and magnesium in peri-operative pain. This may be another potential strategy in the multimodal analgesia regimen.

TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT02309879.
Subcutaneous Injections of Nanofat Adipose-derived Stem Cell Grafting in Facial Rejuvenation
Authors: Menkes Sophie , Luca Mariotta , Soldati Gianni , Polla Luigi 
Published: January 2020

Background:
We aimed to assess whether our novel Nanofat grafting procedure improves skin quality while yielding a regenerative effect and whether this novel technique can also achieve a lifting effect.

Methods:
Patients who requested nonsurgical facial rejuvenation were enrolled between June 2018 and December 2018. Fat was aspirated from the medial thigh, inner part of the knee, or lower abdomen regions. Following aspiration and flushing, microfat was obtained after washing with saline. This microfat was emulsified to obtain a Nanofat suspension, which was injected using a 25-G cannula into the subcutaneous layer at different facial sites. Images were obtained before and at 1, 3, and 6 months after facial rejuvenation. Patients were also administered a survey. Characterization of the isolated stromal vascular fraction (3 patients), and before/after biopsies were performed.

Results:
Fifty patients were included (2 men and 48 women; mean age, 35–65 years; mean follow-up, 9 months). The clinical results were apparent between 2 and 4 weeks after injection, and improvements were continuously observed until 6 months postoperatively. All patients confirmed an improvement in skin quality. A lifting effect was also observed. The data confirm that the Nanofat procedure does not damage cells, maintaining cell viability, and number of adipose-derived stem cells. Biopsies showed an increased dermal cellularity, vascular density, and elastic and collagen fiber density.

Conclusion:
Facial rejuvenation with subcutaneous Nanofat injections appears to be an effective method, representing a skin rejuvenation effect by modifying the pattern of the dermis, although additional studies are necessary.
Restoration of Ear Defects by Prefabricated Radial Forearm Flap
Authors: Trung Vo Thai , Van Long Pham , Van Huynh Thi 
Published: January 2020

Summary:
The case report involved a 36-year-old man. He was injured in a road traffic accident and had extensive third- and fourth-degree facial burns over the right side of his face, with complete loss of his right auricle. We performed a free flap coverage of the right face with the anterolateral thigh (ALT) flap. The reconstruction of his auricle was performed by culturing a cartilage framework on the forearm and transferring it straight to the original location to rebuild the new ear as free flap. Results were assessed 12 months after surgery. The follow-up is still short, but the patient is satisfied with the results achieved.
Lower- and higher-order aberrations after photorefractive keratectomy with and without compensation of pupil centroid shift: fellow eye comparison
Authors: Faramarzi Amir , Hassanpour Kiana , Yazdani Shahin , Moshirfar Majid 
Published: January 2020

Purpose:
To study the effect of pupil centroid shift (PCS) compensation on lower- and higher-order aberrations (HOAs) after photorefractive keratectomy (PRK).

Setting:
Labbafinejad Medical Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Design:
Prospective intrasubject fellow eye study.

Methods:
One hundred twelve eyes of 56 patients with simple myopia or myopic astigmatism scheduled for PRK were enrolled. Preoperatively, the amount of PCS was measured in the horizontal and vertical directions. All eyes received wavefront-optimized treatment with static cyclotorsion compensation. PCS compensation was turned on for the right eye of each subject (PCS-on group), and turned off for the left eye (PCS-off group). Postoperatively, refraction and corneal HOAs were compared between the study groups at 6 months.

Results:
Mean preoperative myopia was −3.84 diopters (D) ± 2.41 (SD) vs −3.75 ± 2.27 D (P = .408), whereas mean preoperative cylinder was −1.18 D ± 1.15 (SD) vs −1.14 ± 1.16 D (P = .769) in the PCS-on and PCS-off groups, respectively. Mean absolute PCS values were 62.25 μm ± 41.82 (SD) vs 55.92 ± 37.47 μm (P = .45) in the horizontal direction and 65.04 ± 47.16 μm vs 58.40 ± 45.44 μm in the vertical direction (P = .29) in the PCS-on and PCS-off groups, respectively. The study groups were comparable in terms of postoperative refraction and root mean square of total corneal HOAs.

Conclusions:
Compensation of PCS did not affect lower- and higher-order aberrations after wavefront-optimized PRK with static cyclotorsion compensation in myopic or myopic astigmatic eyes.
Sex Differences in Prodromal Symptoms and Individual Responses to Acute Coronary Syndrome
Authors: Shi Hongling , Li Wentao , Zhou Xiaohua , Liu Xin , Liu Ju , Fan Shuqin , Wang Huina , An Libin 
Published: January 2020

Background
Although researchers have shown that prodromal symptoms can predict acute coronary events, the ability of patients with acute coronary syndrome (ACS) to identify these symptoms in a timely manner is limited.

Objectives
We aimed to assess prodromal symptoms in Chinese patients with ACS and their responses to symptoms by sex.

Design
This cross-sectional, multicenter study involved 5 teaching hospitals in China and included 806 patients admitted for ACS between June 2013 and February 2014. The McSweeney Acute and Prodromal Myocardial Infarction Symptom Survey (Chinese version) was used to gather data.

Results
Among 806 patients (including 483 women), 688 (85.4%) experienced at least 1 prodromal symptom before ACS onset. Using adjusted logistic regression models, we determined that women were significantly more likely than men to report back pain, between– or under–shoulder blade pain/discomfort, sleep disturbances, anxiousness, or heart racing. The prevalence of generalized chest pain and loss of appetite was higher among men than women. Only 41% of patients attributed their prodromal symptoms to the heart, and women were more likely than men to attribute prodromal symptoms to a heart attack.

Conclusions
More than two-thirds of patients with ACS reported at least 1 prodromal symptom, with some significant sex differences. Most patients do not attribute their symptoms to an impending ACS event.
A contemporary evidence basis for neoadjuvant chemotherapy in upfront resectable pancreatic adenocarcinoma: a systematic review of the literature
Authors: Stonko David P. , He Jin , Zheng Lei , Blair Alex B. 
Published: January 2020

Abstract
Pancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer with poor survival. Local control through surgical resection paired with radiotherapy and chemotherapy comprise the primary tenets of treatment. Debate exists regarding the timing of treatment and ordering of systemic therapy and resection in the management of early stage disease. The goal of this study was to review the literature and describe the contemporary evidence basis for the role of neoadjuvant therapy (NAT) in the setting of upfront resectable (UP-R) PDAC. Five databases were searched in parallel to identify relevant original articles investigating neoadjuvant therapy where at least 1 study arm contained UP-R PDAC; studies with only borderline resectable or locally advanced disease were excluded. Due to the diversity in NAT regimens and study design between trials, qualitative analyses were performed to investigate patient selection, impact on perioperative and survival outcomes, safety, and cost effectiveness. Thirty-five studies met inclusion criteria, of which 24 unique trials are discussed here in detail. These studies included those trials using single agents as well as more recent trials comparing modern multiagent therapies, and several large database analyses. Overall the data suggest that NAT is safe, may confer survival benefit for appropriately selected patients, is cost effective, and is an appropriate approach for UP-R PDAC. Nevertheless, the risk for disease progression during upfront medical therapy, requires appropriate patient identification and close monitoring, and emphasizes the need for further discovery of more effective chemotherapeutics, useful biomarkers or molecular profiles, and additional prospective comparative studies.
Critical care considerations in the management of acute-on-chronic liver failure
Authors: MacDonald Andrew John , Olson Jody , Karvellas Constantine J. 
Published: January 2020

Purpose of review
Patients with cirrhosis are frequently hospitalized with acute decompensation and organ system failure – a syndrome referred to as acute on chronic liver failure (ACLF). These patients often require critical care intervention and experience significant mortality; however, established diagnostic and prognostic criteria are lacking. Given this, it remains imperative for intensivists to develop an expertise in common ACLF complications and management.

Recent findings
Liver transplantation serves as the definitive management strategy in ACLF. Traditional organ allocation procedures are based on the Model for Endstage Liver Disease score, which may not correlate with ACLF severity and the associated need for urgent liver transplantation. Recent studies have suggested favorable postliver transplantation outcomes in ACLF patients with multiorgan failure, emphasizing the need for further studies to elucidate optimal timing and candidacy for liver transplantation.

Summary
Cirrhosis is a chronic and progressive condition leaving patients vulnerable to acute decompensation necessitating the need for critical care intervention. Prompt recognition and implementation of targeted supportive therapies, together with consideration of urgent liver transplantation, are essential to combat the high short-term mortality of ACLF patients.