bluuebunny/crossref_metadata_2025_split huggingface dataset:
Anti-cyclic citrullinated peptide antibody is highly associated with rheumatoid factor and radiological defects in rheumatoid arthritis patients
Authors: Sulaiman Farah Nadiah , Wong Kah Keng , Ahmad Wan Aireene Wan , Ghazali Wan Syamimee Wan 
Published: March 2019

Abstract
Rheumatoid arthritis (RA) is a chronic debilitating inflammatory disease affecting mainly the joint, surrounding tissue and other extra-articular structures in the body. RA can lead to destruction of bone and cartilage which may cause severe disability and it is characterized by the presence of serum rheumatoid factor (RF). The anti-cyclic citrullinate peptide (anti-CCP) antibody is another serum biomarker used in RA diagnosis with higher sensitivity and specificity.
In this cross-sectional study with retrospective record review, 159 established RA patients from Hospital Universiti Sains Malaysia (HUSM) were recruited. Enzyme-linked immunosorbent assays (ELISAs) for serum RF and anti-CCP were performed. Our goal was to evaluate the significance of anti-CCP antibody in predicting the disease activity and progression in terms of radiological and extra-articular manifestations upon diagnosis.
Of the 159 RA patients included in this study, mean age was 48.3 years old and majority (n = 134; 84.3%) were female. A total of 83 (52.2%) and 99 (62.3%) patients had anti-CCP antibody and RF, respectively. Mean Disease Activity Score-28 for Rheumatoid Arthritis with erythrocyte sedimentation rate (ESR) (DAS28-ESR) score for all patients was 4.74 (medium and high disease activity). Fifty-eight (36.5%) patients had radiological defects and 49 (30.8%) patients had extra-articular involvement manifested by rheumatoid nodule, pulmonary involvement, and anemia.
In terms of anti-CCP antibody association with clinical and laboratory parameters, a significant co-occurrence of RF and anti-CCP antibody (P = .002) was observed. Anti-CCP antibody was significantly associated with radiological defects in which majority of patients with such defects (n = 40/58; 68.9%) were positive for anti-CCP antibody (P = .001). However, there was no significant difference between mean and classes of disease activity score and extra-articular manifestations between different anti-CCP antibody groups. In addition, extra-articular manifestations were not associated with high disease activity upon RA diagnosis
There was a significant association between anti-CCP antibody positivity and positive RF. Radiological defects were the sole clinical parameter significantly associated with anti-CCP antibody positivity, indicating that patients positive for anti-CCP antibody should be routinely monitored for radiological defects and their onset.
Fibroblast growth factors in control of lipid metabolism: from biological function to clinical application
Authors: Struik Dicky , Dommerholt Marleen B. , Jonker Johan W. 
Published: March 2019

Purpose of review
Several members of the fibroblast growth factor (FGF) family have been identified as key regulators of energy metabolism in rodents and nonhuman primates. Translational studies show that their metabolic actions are largely conserved in humans, which led to the development of various FGF-based drugs, including FGF21-mimetics LY2405319, PF-05231023, and pegbelfermin, and the FGF19-mimetic NGM282. Recently, a number of clinical trials have been published that examined the safety and efficacy of these novel therapeutic proteins in the treatment of obesity, type 2 diabetes (T2D), nonalcoholic steatohepatitis (NASH), and cholestatic liver disease. In this review, we discuss the current understanding of FGFs in metabolic regulation and their clinical potential.

Recent findings
FGF21-based drugs induce weight loss and improve dyslipidemia in patients with obesity and T2D, and reduce steatosis in patients with NASH. FGF19-based drugs reduce steatosis in patients with NASH, and ameliorate bile acid-induced liver damage in patients with cholestasis. In contrast to their potent antidiabetic effects in rodents and nonhuman primates, FGF-based drugs do not appear to improve glycemia in humans. In addition, various safety concerns, including elevation of low-density lipoprotein cholesterol, modulation of bone homeostasis, and increased blood pressure, have been reported as well.

Summary
Clinical trials with FGF-based drugs report beneficial effects in lipid and bile acid metabolism, with clinical improvements in dyslipidemia, steatosis, weight loss, and liver damage. In contrast, glucose-lowering effects, as observed in preclinical models, are currently lacking.
Rethinking what constitutes a diagnosis in the genomics era: a critical illness perspective
Authors: Lakhani Saquib A. , Pierce Richard 
Published: March 2019

Purpose of review
The purpose of this review is to highlight the significant advances in the testing, interpretation, and diagnosis of genetic abnormalities in critically ill children and to emphasize that pediatric intensivists are uniquely positioned to search for genetic diagnoses in these patients.

Recent findings
Ten years following the first clinical diagnosis made through whole exome sequencing, we remain in the dark about the function of roughly 75% of our genes. However, steady advancements in molecular techniques, particularly next-generation sequencing, have spurred a rapid expansion of our understanding of the genetic underpinnings of severe congenital diseases. This has resulted in not only improved clinical diagnostics but also a greater availability of research programs actively investigating rare, undiagnosed diseases. In this background, the scarcity of clinical geneticists compels nongeneticists to familiarize themselves with the types of patients that could benefit from genetic testing, interpretations of test results as well as the available resources for these patients.

Summary
When caring for seriously ill children, critical care pediatricians should actively seek the possibility of an underlying genetic cause for their patients’ conditions. This is true even in instances when a child has a descriptive diagnosis without a clear underlying molecular genetic mechanism. By promoting such diagnostics, in both clinical and research settings, pediatric intensivists can advance the care of their patients, improve the quality of information provided to families, and contribute to the knowledge of broad fields in medicine.
Self-Reported Infertility and Associated Pelvic Inflammatory Disease Among Women of Reproductive Age—National Health and Nutrition Examination Survey, United States, 2013–2016
Authors: Anyalechi Gloria Ebelechukwu , Hong Jaeyoung , Kreisel Kristen , Torrone Elizabeth , Boulet Sheree , Gorwitz Rachel , Kirkcaldy Robert D. , Bernstein Kyle 
Published: March 2019

Background
Sexually transmitted diseases, including chlamydia and gonorrhea, cause of pelvic inflammatory disease (PID) and infertility. We estimated the prevalence of infertility and infertility health care seeking.

Methods
We analyzed self-reported lifetime infertility and infertility health care-seeking in women aged 18 to 49 years in the 2013 and 2015 National Health and Nutrition Examination Surveys. Weighted prevalence of infertility and infertility health care seeking, prevalence ratios (PRs), and 95% confidence intervals (CIs) were calculated.

Results
Among 2626 eligible women, 13.8% had self-reported infertility (95% CI, 12.3–15.3) with higher prevalence by age: 960, 18 to 29 years (PR, 6.4%; 95% CI, 4.8–8.0); 799, 30 to 39 years (PR, 14.8%; 95% CI, 12.2–17.3); and 867, 40 to 49 years (PR, 20.8%; 95% CI, 17.2–24.4). Non-Hispanic white women (PR, 15.4%; 95% CI, 13.0–17.8; n = 904) and non-Hispanic black women (PR, 12.9%; 95% CI, 10.3–15.5; n = 575) had the highest infertility prevalences. Women reporting PID treatment (n = 122) had higher infertility prevalence (PR, 24.2%; 95% CI, 16.2–32.2) than women without PID treatment (PR, 13.3%; 95% CI, 11.6–15.0; n = 2,485), especially among 18- to 29-year-old women (PR, 3.8; 95% CI, 1.8–8.0). Of 327 women with infertility, 60.9% (95% CI, 56.1–65.8) sought health care. Women without health care insurance sought care less frequently than women with insurance.

Conclusions
In a nationally representative sample, 13.8% of reproductive-age women reported a history of infertility, of whom 40% did not access health care. Self-reported PID was associated with infertility, especially in young women. Annual chlamydia and gonorrhea screening to avert PID may reduce the burden of infertility in the United States.
Sexually Transmitted Disease, Human Immunodeficiency Virus, and Pregnancy Testing Behaviors Among Internet and Mobile Dating Application Users and Nonusers, 2016
Authors: Coor Alexandra , Kachur Rachel , Friedman Allison , Witbart Lauren , Habel Melissa A. , Bernstein Kyle , Hogben Matthew 
Published: March 2019

Abstract
We examined 2016 United States market research to understand the demographics and sexual health testing behaviors of dating app users. Internet/app users were more likely to be young adults, male, nonwhite, of Hispanic ethnicity, and unmarried. Users also reported greater testing for sexually transmitted disease, human immunodeficiency virus, and pregnancy.
Perioperative Therapies—Using Repurposed Drugs to Improve Cancer Surgery Outcomes
Authors: Pantziarka Pan , Bouche Gauthier 
Published: March 2019

Aims
Reducing the rate of recurrence after curative-intent surgical resection is an attractive strategy for improving long-term survival in cancer. Perioperative therapies administered in the period immediately prior to, during, or after surgery therefore hold the potential to improve overall survival. Drug repurposing is a source of therapeutic candidates for further clinical investigation. We aimed to identify noncancer drugs with the potential to be repurposed as perioperative therapies.

Methods
The Repurposing Drugs in Oncology repurposing database and PubMed were used for a literature-based search of publications related to perioperative treatment of cancer. Three clinical trials registries were also searched to identify relevant clinical trials with survival endpoints. Both the literature and trial screens were supplemented with additional data known to the authors.

Results
Fifty-two drugs were identified as potential perioperative therapies, with 67% having supporting human data. There are few clinical trials with survival endpoints, mainly in breast and colorectal cancers.

Discussion
The perioperative setting is not as well established as the neoadjuvant and adjuvant settings, making identification of relevant research and clinical trials difficult. Despite the potential benefits of such interventions, there is a need for more well-designed clinical trials, additional research, and biomarkers of response.
Transcriptome Signature Reversion as a Method to Reposition Drugs Against Cancer for Precision Oncology
Authors: Koudijs Karel K. M. , Terwisscha van Scheltinga Anton G. T. , Böhringer Stefan , Schimmel Kirsten J. M. , Guchelaar Henk-Jan 
Published: March 2019

Abstract
Transcriptome signature reversion (TSR) has been hypothesized as a promising method for discovery and use of existing noncancer drugs as potential drugs in the treatment of cancer (i.e., drug repositioning, drug repurposing). The TSR assumes that drugs with the ability to revert the gene expression associated with a diseased state back to its healthy state are potentially therapeutic candidates for that disease. This article reviews methodology of TSR and critically discusses key TSR studies. In addition, potential conceptual and computational improvements of this novel methodology are discussed as well as its current and possible future application in precision oncology trials.
Patient-Centered Outcomes and Key Study Procedure Finalization in the Pilot Feasibility Gout Randomized Trial
Authors: Singh Jasvinder A. , Willig Amanda L. , Darnell Betty , Green Candace , Morgan Sarah , Weiss Rick , Saag Kenneth G. , Cutter Gary , McGwin Gerald 
Published: March 2019

Objective
The aim of this study was to report patient-centered outcomes and finalization of key study procedures from a 9-month pilot internet randomized controlled trial of cherry extract versus diet modification.

Methods
We randomized 84 people with physician-confirmed gout in an internet study to cherry extract (n = 41) or dietitian-assisted diet modification for gout (n = 43). All study outcomes were collected via internet and phone calls. We finalized key study procedures. We assessed acceptability and feasibility of the intervention and satisfaction with study website.

Results
Study participant satisfaction with the intervention was high. The intervention was perceived as easy, enjoyable, understandable, and helpful (scores 65–88 for all; higher = better). The amount of time spent for the study was acceptable. Participant satisfaction with website interaction and content was very high; 85% or more were moderately to extremely satisfied. Significantly lower total calories, total carbohydrate, and saturated fat intake were noted at 6 months in the diet modification versus cherry extract group; differences were insignificant at 9 months. Six of the 8 Health Assessment Questionnaire sections/domains improved significantly from baseline to 9 months in cherry extract versus 2 Health Assessment Questionnaire sections/domains in the diet modification group. Key study procedures were finalized for a future trial, including an internet diet assessment tool, gout flare assessment, provider confirmation of gout diagnosis, patient reporting of classification criteria, and centralized laboratory-assisted serum urate testing.

Conclusions
High patient acceptability and feasibility of study/intervention and finalization of key study procedures indicate that hypothesis-testing internet gout trials of cherry extract and/or diet modification can be conducted in the future.
Helical Rim Reconstruction With Chondrocutaneous Hatchet Flap-Z Plasty
Authors: Durğun Mustafa , Baş Soysal 
Published: March 2019

Background
Helical rim reconstruction is relatively difficult because of the unique anatomical structure of the ear. The aesthetic and functional characteristics of the ear make such reconstruction even more important. This article presents the newly defined chondrocutaneous hatchet flap-Z plasty (HFZP) method in helical rim defects and evaluates the results.

Methods
This study retrospectively evaluates 14 patients who were operated on using the chondrocutaneous HFZP method after a tumor excision located on the helical rim. The etiologies of the patients were basal cell carcinoma (n = 7), squamous cell carcinoma (n = 2), and actinic keratosis (n = 5). All patients were operated on under local anesthesia. The patients were evaluated regarding age, sex, etiology, defect location, and aesthetic outcomes.

Result
Five patients were female, and 9 were male. The mean age of the patients was 72.2 years. Nine tumors were localized in the upper one-third of the helical rim, and 5 were localized in the middle one-third. The average duration of operation was 24 minutes. The aesthetic results were 11 patients (78.59%) who recovered with excellent outcome, 2 patients (14.2%) with good outcome, and 1 patient(7.1%) with poor outcome. There were no postoperative complications, such as flap necrosis, infection, suture detachment hemorrhage, or hematoma.

Conclusions
The chondrocutaneous HFZP method is a simple, single-stage method that uses local tissues without color mismatch. In addition to the method's geometric gain, there is no removal of healthy skin or cartilage, resulting in minimal decreases in the vertical and horizontal diameters of the ear.
Intraoperatively Detected But Previously Indocyanine Green–Negative Lymphatic Vessels May Have Misprized Potentials and Should Not Be Neglected in Lymphaticovenous Bypass Surgery
Authors: Scaglioni Mario F. , Uyulmaz Semra , Arvanitakis Michael , Lineaweaver William C. , Zhang Feng 
Published: March 2019

Introduction
Identification of patent lymphatic vessels without fibrosis and with high flow is difficult but crucial in the preoperative planning of lymphaticovenous anastomosis (LVA). Lymphatic vessels on the operating field cannot always be visualized preoperatively because of the anatomical and physiological characteristics of lymphedema tissue. The purposes of this study were to demonstrate our clinical experience in identifying indocyanine green (ICG)–negative lymphatics intraoperatively and to emphasize the therapeutic potential of performing anastomoses with ICG-negative lymphatics.

Methods
Indocyanine green–positive lymphatic ducts were marked preoperatively in 5 patients with lower extremity lymphedema; moreover, if ICG-negative lymphatics were identified during surgery, they were used for additional LVA thus implementing multiple anastomoses in one surgical setting.

Results
In total, 33 LVAs were performed in 5 patients with lower extremity lymphedema, of which 11 LVAs were implemented with ICG-negative lymphatics. Immediately after the anastomosis, a strong lymphatic drainage could be appreciated in all cases. Six months postoperatively patients reported a subjective decrease in limb circumference and pressure sensation.

Conclusions
We believe that ICG-negative lymphatics found intraoperatively should be evaluated for additional LVAs in order to maximize drainage effect and might provide better outcomes.
Clinical and Molecular Study of ELMO-2–Related Massive Intraosseous Vascular Malformations
Authors: Vargel Ibrahim , Calis Mert , Canter Halil Ibrahim , Cil Barbaros Erhan 
Published: March 2019

Abstract
Massive intraosseous vascular malformations, a relatively rare entity in the vascular malformation spectrum, deserves attention as involving the membranous bones of the craniofacial skeleton and may lead to severe life-threatening hemorrhages and even death. The main aim of this study was to summarize the 25 years of clinical experience with these vascular malformation osseous patients, focus on the molecular and genetic aspect of the clinical entity, and to emphasize the certain challenging conditions in the treatment of these patients. All the patients appeared to be unaffected at birth, whereas initial symptoms occasionally began with painless swelling in the mandible in early childhood. The disease was progressive in behavior especially in the pubertal ages and was specifically involving the maxilla and mandible of the craniofacial skeleton in all the patients. Calvarium and cranial base were the second most common involved regions among these patients (62.5%). Clavicular (50%), costal (25%), and vertebral (25%) involvements were also a significant manifestation of the disease. Tissue samples obtained from the affected individuals and the blood samples from their families were matched, revealing a loss of function mutation in the ELMO-2 gene of chromosome 20 leading to developmental abnormality of the vascular structures via RAC1 signaling and leading to abnormally enlarged vessels in the intraosseus portion of the membranous bone. Immunohistochemical staining revealed positive CD31 and smooth muscle actin staining but negative proliferation and maturity markers such as Ki-67, desmin, h-caldesmon, and myofibroblast-like desmin. The follow-up of 3 of 5 patients ended up with mortality (60%). vascular malformation osseous is intraosseous vascular malformation with aggressive biological behavior associated with ELMO-2 gene mutation. Further studies for obtaining prenatal diagnosis and achievement of gene therapy should take place. As the disease rapidly progresses as the affected individual grows, surgical interventions should be taken into consideration before the initiation of complications.
Pocket Irrigation and Technique During Reconstructive Surgery
Authors: Epps Mathew Thomas , Langsdon Sarah , Pels Taylor K. , Noyes Victoria , Levine David , Thurston Todd E. , Spratt Henry G. , Brzezienski Mark A. 
Published: March 2019

Background
Expander-to-implant is the most common breast reconstruction procedure in the United States. Irrigation with triple antibiotic solution (TAS), as described by Adams et al in 2006, has become standard of care to lower bacterial bioburden. However, several alternative solutions have been implemented with the literature lacking a consensus regarding use (Plast Reconstr Surg. 2006;117:30-36).

Objective
We distributed a peer-reviewed survey among a cohort of American Society of Plastic Surgery (ASPS) members to assess pocket irrigation technique during implant-based reconstructive surgery. We then conducted a pilot in vitro study to determine antibacterial efficacy of the most preferred irrigation at preferred dwell times against select bacterial species linked to breast pocket contamination during reconstructive implant-based surgery.

Methods
The survey was distributed a total of 3 times to a random cohort of 2488 ASPS members in January 2018. During in vitro studies, pure cultures of common breast flora were exposed to TAS versus saline control at 1, 2, and 5 minutes in a simulated in vivo cavity. Viable plate counts were used to assess cell viability.

Results
The response rate was above the ASPS survey average at 16% (n = 407). The population reflected a cross-section of practice types and experience levels. Triple antibiotic solution without Betadine was the favored irrigation at 41%, with 73% of its users preferring dwell times of 2 minutes or less. Over 30 distinct breast pocket irrigation solutions were identified. Bacteria added to the in vivo cavity survived a 2-minute dwell time with TAS as follows: 51% Staphylococcus epidermidis, 69% Escherichia coli, 88% Enterococcus faecalis, 88% Pseudomonas aeruginosa, and 98% Acinetobacter baumannii.

Conclusion
Our survey data demonstrate significant variability in practice and lack of consensus among ASPS members regarding antimicrobial irrigation during reconstructive breast surgery. Our in vitro data underscores the importance of relating clinical practices with laboratory studies of microorganisms potentially linked to breast pocket contamination and suggests that TAS requires either dwell times greater than 5 minutes and/or the inclusion of efficacious antimicrobial agents (eg, Betadine). This finding has the potential to impact antimicrobial pocket irrigation and technique during breast reconstruction.