bluuebunny/crossref_metadata_2025 huggingface dataset:
The Predicament of Gastrointestinal Bleeding in Patients With a Continuous-Flow Left Ventricular Assist Device
Authors: Berg Dana , Lebovics Edward , Kai Masashi , Spielvogel David
Published: October 2018

Heart failure affects over 5 million Americans, with numbers expected to rise. While heart transplantation is the most effective long-term strategy for end-stage heart failure, there is a limited cardiac donor pool, and these organs are often unavailable at the time of need. Left ventricular assist devices, therefore, continue to be used to bridge this gap. Originally implanted as a bridge to transplant, these devices are now additionally utilized as destination therapy for patients ineligible for transplant. With the widespread applicability of these devices for not just temporary measures, but also for prolonged use, the short- and long-term impact on other organ systems has become more evident. For example, gastrointestinal (GI) bleeding, with an incidence approaching 30%, is one such complication post–continuous-flow left ventricular assist device implantation. This high incidence of GI bleeding is thought to stem from a combination of factors, including the need for concomitant anticoagulant and antiplatelet therapy, and intrinsic device-related properties resulting in acquired Von Willebrand disease and arteriovenous malformations. Due to the significant morbidity associated with these GI bleeding events, a standardized protocol optimizing medical and endoscopic management, alongside close coordination between the gastroenterology and cardiology services, should be advocated for and ultimately employed.
ROLE OF DIAGNOSTIC PARS PLANA VITRECTOMY IN DETERMINING THE ETIOLOGY OF UVEITIS INITIALLY UNKNOWN
Authors: Zhao Xin-yu , Xia Song , Chen You-xin
Published: October 2018

Purpose:

To estimate the success and safety of diagnostic pars plana vitrectomy (PPV) in determining the etiology of uveitis initially unknown and analyze their characteristics.

Methods:

The PubMed, Embase, and Ovid were searched up to October 2017 to identify relevant studies. The PRISMA guidelines were followed. Statistical analyses were performed with R version 3.3.1. Result in proportion were transformed by the Freeman–Tukey variant of arcsine square to attain symmetry of confidence intervals (CIs). The statistical heterogeneity was assessed by the chi-square test and I2 statistics. Sensitivity analysis and subgroup analyses were performed to identify the source of heterogeneity. Publication bias was assessed by the Egger test.

Results:

Sixteen studies involving 1,195 patients were finally included. The pooling result showed the successful rate of diagnostic PPV was 44% (95% CI [39%∼50%]). Among patients whose diagnostic PPV yielded a definitive diagnosis, 69% were infectious uveitis (95% CI [61%∼77%]), 23% were lymphoma (95% CI [17%∼30%]), and 4% were metastatic carcinoma (95% CI [2%∼10%]). Among patients diagnosed with infectious uveitis, the most frequent pathogens identified were viruses, followed by bacteria, Toxocara canis, Toxoplasma gondii, tuberculosis, and fungus. The incidence of postoperative cataract and postoperative retinal detachment was 19% (95% CI [8%∼29%]) and 5% (95% CI [1%∼10%]), respectively, and the rate of secondary vitrectomy surgery was 10% (95% CI [2%∼22%]). Postoperative visual improvement rate was 46% (95% CI [39%∼52%]), and the postoperative treatment strategy was changed in light of the results of diagnostic PPV in 20% of cases (95% CI [10%∼29%]).

Conclusion:

For uveitis of unknown cause, diagnostic PPV is an effective, reliable, and relatively safe procedure for establishing the definite diagnosis and guiding further treatment. Positive therapeutic effect could also be achieved.
CLINICAL PRESENTATIONS, DIAGNOSIS, AND MANAGEMENT OUTCOMES OF CURVULARIA ENDOPHTHALMITIS AND A REVIEW OF LITERATURE
Authors: Dave Vivek Pravin , Joseph Joveeta , Pathengay Avinash , Pappuru Rajeev R. , Das Taraprasad
Published: October 2018

Purpose:

To describe the clinical presentation and management of Curvularia endophthalmitis and compare with previous published literature.

Methods:

Retrospective interventional comparative case series and literature review. Eight cases with culture-proven Curvularia endophthalmitis from January 2000 to March 2018 underwent vitrectomy/vitreous biopsy, intravitreal antibiotic with or without additional procedures as appropriate. The undiluted vitreous biopsy was subjected to microbiologic evaluation. Pre-existing literature was reviewed, and the current outcomes were compared with them. The mean age at presentation, etiology, number of interventions, interval between inciting event and presentation, type of intravitreal antifungal used, anatomical, and the functional outcomes were reported and compared with pre-existing literature. A favorable anatomical outcome was defined as preservation of the globe, absence of hypotony, attached retina, and absence of active inflammation at the last visit.

Results:

In the current series, there were 4 men and 4 women. Mean age at presentation was 34.5 ± 13.51 years (median 30 years). Inciting event was open-globe injury in five cases and cataract surgery, trabeculectomy, and endogenous cause in one case each. Presenting visual acuity was ≥20/400 in 3 cases at presentation and 5 cases at the last visit. One case with staphyloma and endophthalmitis underwent evisceration for a painful blind eye. The patients in the current series were much younger than those described previously.

Conclusion:

Presentation and diagnosis of Curvularia can be delayed especially in postoperative cases. Early and appropriate management with multiple interventions can result in an acceptable visual and anatomical outcome.
EPSTEIN–BARR VIRUS ACUTE RETINAL NECROSIS IN AN IMMUNOCOMPETENT HOST
Authors: Chan Errol W. , Sun Vincent , Eldeeb Mohab , Kapusta Michael A.
Published: October 2018

Purpose:

To describe a case of Epstein–Barr virus (EBV)-associated acute retinal necrosis (ARN) in an immunocompetent patient and to summarize the clinical features of published molecularly confirmed EBV–ARN cases.

Methods:

Case report and literature review.

Results:

An 83-year-old immunocompetent woman with unilateral ARN presented with visual acuity of light perception. Oral valacyclovir was started. One week later, vitrectomy was conducted for worsening inflammation. Intraoperatively, a severe confluent necrotizing retinitis and occlusive vasculitis involving all four quadrants of posterior and peripheral retina were noted. Vitreous polymerase chain reaction was exclusively positive for EBV. Other autoimmune, infective, and hematological work-up was negative. The retinitis resolved 3 months later, but with significant macular and generalized retinal atrophy, visual acuity remained light perception. From the literature, there are four EBV–ARN cases (six eyes) diagnosed based on polymerase chain reaction or fluorescence in-situ hybridization of vitreous or retinal samples. All patients were immunocompromised or on immunosuppressive treatment. Presenting visual acuity was light perception or worse in 3/6 eyes. Three patients received systemic acyclovir-based therapy. Vitrectomy was performed in 4/6 eyes between 4 and 8 weeks from disease onset. All cases had involvement of the posterior and peripheral retina. Retinal detachment occurred in 2/6 eyes, and final visual acuity was no light perception in 3/6 eyes.

Conclusion:

This case expands the clinical spectrum of EBV–ARN to include infection in immunocompetent hosts. Epstein–Barr virus–ARN seems to be characterized by a global peripheral and posterior fulminant retinitis, with adverse visual acuity outcomes despite systemic acyclovir-based therapy. The benefits of adjunctive intravitreal foscarnet, systemic steroids, and early vitrectomy may warrant further investigation.
Randomized Study of Collagen Cross-Linking With Conventional Versus Accelerated UVA Irradiation Using Riboflavin With Hydroxypropyl Methylcellulose: Two-Year Results
Authors: Hagem Anne Marie , Thorsrud Andreas , Sandvik Gunhild Falleth , Drolsum Liv
Published: October 2018

Purpose:

To compare the clinical outcome 2 years after corneal collagen cross-linking (CXL) with conventional and accelerated ultraviolet A (UVA) irradiation using riboflavin with hydroxypropyl methylcellulose.

Methods:

Prospective randomized controlled study. Forty patients with keratoconus (40 eyes) were randomized to either CXL using conventional 3 mW/cm2 UVA irradiation for 30 minutes (CXL30 group) or accelerated 9 mW/cm2 UVA irradiation for 10 minutes (CXL10 group). In both groups, a solution of 0.1% riboflavin with 1.1% hydroxypropyl methylcellulose (methylcellulose–riboflavin) was used. Uncorrected distance visual acuity, corrected distance visual acuity (CDVA), and Scheimpflug tomography were performed at baseline and after 24 months.

Results:

Both groups had statistically significant improvement in CDVA and maximum keratometric reading compared with baseline; however, with no statistically significant difference in the change between the 2 groups. No significant changes in flattest, steepest and mean keratometry (K1, K2 and K mean) were found in either of the groups. There were no statistically significant changes in ECD in either group after 2 years or in the difference in the change between the 2 groups. A literature review showed comparative clinical outcome after accelerated CXL compared with conventional CXL; however, in several studies, there was a tendency for less pronounced corneal flattening after accelerated CXL.

Conclusions:

Improvement in visual acuity and maximum keratometric reading 2 years after CXL was found after both conventional and accelerated UVA irradiation using methylcellulose–riboflavin. This suggests that when using riboflavin with methylcellulose, the less time-consuming accelerated protocol is a valuable and effective option in CXL treatment.
Classification of Limbal Stem Cell Deficiency Using Clinical and Confocal Grading
Authors: Aravena Carolina , Bozkurt Kansu , Chuephanich Pichaya , Supiyaphun Chantaka , Yu Fei , Deng Sophie X.
Published: October 2018

Purpose:

To grade the severity of limbal stem cell deficiency (LSCD) based on the extent of clinical presentation and central corneal basal epithelial cell density (BCD).

Methods:

This is a retrospective observational comparative study of 48 eyes of 35 patients with LSCD and 9 eyes of 7 normal subjects (controls). Confocal images of the central cornea were acquired. A clinical scoring system was created based on the extent of limbal and corneal surface involvement. LSCD was graded as mild, moderate, and severe stages based on the clinical scores. The degree of BCD reduction was given a score of 0 to 3.

Results:

Compared with BCD in controls, BCD decreased by 23.0%, 40.4%, and 69.5% in the mild, moderate, and severe stages of LSCD classified by the clinical scoring system, respectively. The degree of BCD reduction was positively correlated with larger limbal and corneal surface involvement and when the central visual axis was affected (all P ≤ 0.0005). Mean corrected distance visual acuity logarithm of the minimum angle of resolution was 0.0 ± 0.0 in control eyes, 0.2 ± 0.5 in mild LSCD, 0.6 ± 0.4 in moderate LSCD, and 1.6 ± 1.1 in severe LSCD (P < 0.0001). There was a significant correlation between a higher clinical score and corrected distance visual acuity logarithm of the minimum angle of resolution (rho = 0.82; P < 0.0001) and a greater decrease in BCD (rho = −0.78; P < 0.0001).

Conclusions:

A clinical scoring system was developed to assess the extent of clinical presentation of LSCD. A classification system to grade the severity of LSCD can be established by combining the BCD score with the clinical score.
Mechanistic pain profiling as a tool to predict the efficacy of 3-week nonsteroidal anti-inflammatory drugs plus paracetamol in patients with painful knee osteoarthritis
Authors: Petersen Kristian Kjær , Olesen Anne Estrup , Simonsen Ole , Arendt-Nielsen Lars
Published: October 2018

Joint inflammation is present in a subpopulation of knee osteoarthritis (OA) patients. Proinflammatory cytokines are known to sensitize the peripheral and central pain pathways. This can be mechanistically assessed by pressure pain thresholds and temporal summation of pain (TSP). Nonsteroidal anti-inflammatory drugs (NSAIDs) combined with paracetamol are recommended as OA treatment. The current study hypothesized that evidence of central sensitization would predict poor responses to peripherally directed therapies in knee OA and therefore aimed to investigate the value of mechanistic pain profiling for predicting pain outcome of treatment with NSAIDs plus paracetamol. One hundred thirty-two patients received ibuprofen 1200 mg/daily, paracetamol 3 g/daily, and pantoprazole 20 mg/daily for 3 weeks. Before administration, cuff pain detection, tolerance threshold, and TSP were assessed. Worst pain within the last 24 hours and pain during activity (visual analogue scales) were assessed before and after treatment. Facilitated TSP was found at baseline in the nonresponders to the 3-weeks treatment as compared to responders for both the 30% and 50% pain alleviation criteria (P < 0.02). Linear regression models identified facilitated TSP (P < 0.01) and low clinical pain scores (P < 0.001) as independent factors for prediction of poor pain alleviation by the treatment. In conclusion, this study found that mechanistic pain profiling can predict pain alleviation of NSAIDs and paracetamol. Facilitated TSP and low clinical pain scores before treatment are independent predictors of poor pain alleviation after NSAIDs and paracetamol. This study adds to the growing evidence that a subgroup of knee OA patients with manifested central sensitization may require special management attention.
A Tailored Dietary Sodium Intervention Using Technology and Psychosocial Support
Authors: Heo Seongkum , McSweeney Jean , Prewitt T. Elaine , Lee Jeannette Y. , Moser Debra K. , Shaw-Devine Allison , Morell Audrey , Kim JinShil , Yeary Karen H. K.
Published: October 2018

Background

In patients with heart failure (HF), high dietary sodium intake is common and associated with HF symptoms, poor health-related quality of life (HRQOL), and high hospitalization rates.

Purpose

The aims of this study were to examine the feasibility of a tailored dietary intervention with a practical tool (MyFitnessPal) and to obtain preliminary data about the effects on sodium intake, factors affecting sodium intake (knowledge, skills, experiences, confidence, perceived benefits and barriers, and depressive symptoms), HF symptoms, and HRQOL.

Methods

A 6-session intervention was delivered to 11 participants. Paired t tests were used to compare the baseline outcomes with those at 3 months.

Results

Participants completed 98% of intervention sessions, and 91% used MyFitnessPal. Sodium intake was reduced, and factors affecting sodium intake, symptoms, and HRQOL were improved (all P < .05).

Conclusion

The intervention was feasible and warrants further research to test the effects of the intervention on the outcomes using larger, heterogeneous samples.
A Method to Study the Effect of a Physician Assistant Student on Preceptor Productivity
Authors: Evans Timothy C. , Wick Keren H. , Andrilla C. Holly A. , Skaggs Steven A. , Burgin Tiffani
Published: October 2018

Purpose

Guided clinical experience is a critical component of a physician assistant (PA) student's education. However, clinical precepting is strongly perceived to have deleterious effects on productivity. In this study, we sought to test a method for evaluating the effect that PA students have on clinical productivity.

Methods

We recruited 14 family medicine preceptors and second-year PA students from 2 programs, the University of Washington (UW) and the University of Texas Health Science Center San Antonio (UT). We collected productivity data during 3 weeks of preceptor clinical practice—one week without a PA student present and 2 weeks with a PA student present (one week early in the student's family medicine clinical rotation and a second week late in the rotation). We collected preceptor demographic data, patient characteristics, and the primary outcome—relative value units (RVUs) per preceptor per half-day during the 3 data collection weeks. At the end of the study, we asked preceptors about the ease of data collection and any negative effects of the study itself on their clinical productivity.

Results

No significant differences were found in preceptor demographics or in patient characteristics, numbers of patients, or RVUs per patient seen in any of the weeks or between UW and UT. In this pilot study, no significant differences were seen in RVUs per preceptor per half-day between the 3 weeks of observation or between UW and UT.

Conclusion

In this pilot study, the protocol was straightforward, unintrusive, and preliminarily showed no significant effects of a PA student on preceptor productivity.
Nonoperative Applications of Placental Tissue Matrix in Orthopaedic Sports Injuries: A Review of Literature
Authors: Sultan Assem A. , Piuzzi Nicolas S. , Mont Michael A.
Published: October 2018

Objective:

Recently, various amniotic tissue and placental-based tissue matrix (PTM) products have become increasingly available as a nonoperative treatment for tendinopathies and orthopaedic sports injuries. The aim of this review was to evaluate: (1) safety and efficacy of nonoperative use of PTM products, in acute and chronic tendon injuries and (2) the commercially available tissue options to better understand their differences.

Data Sources:

A comprehensive literature search was performed. Inclusion criteria were studies reporting on: (1) nonoperative uses of PTM therapy in sports injuries; and (2) clinical outcomes; in (3) human subjects. We excluded: (1) animal studies; (2) basic science studies; (3) non-English language literature; (4) review articles; and (5) duplicate studies. In addition, to determine the various product formulations, their tissue contents, and indications for use, we searched publicly available website content, marketing literature, and Food and Drug Administration (FDA) registration documents.

Main Results:

Current evidence investigated various PTM products for the treatment of various tendon injuries with demonstrated efficacy mainly in the short term with follow-up ranging between 6 weeks and 3 months. In addition, across all studies, no specific adverse events were reported. Substantial differences exist among the currently available products due to variations in their tissue source, formulations, processing methods, method of sterilization, preservation, and storage, indications for use, and FDA regulation.

Conclusions:

Placental- and amniotic membrane–derived tissues seem to be safe for the nonoperative treatment of tendinopathies. However, several factors may affect the efficacy and safety profile of these products, and the orthopaedic surgeons should be aware of the differences.
Identifiable Factors Associated With Acceptance Into Sports Medicine Fellowship Programs: A Brief Report
Authors: Zaremski Jason L. , Rao Ashwin , Myers Rebecca , Mautner Ken , Berkoff David , Ross David , Logan Kelsey , Horodyski MaryBeth , Asif Irfan M.
Published: October 2018

Objective:

To identify factors associated with entry into primary care sports medicine (PCSM) fellowship programs.

Design:

Primary care sports medicine fellowship directors (FDs) and fellowship faculty were surveyed regarding preferences for accepting applicants into their programs.

Setting:

Survey study.

Participants:

Primary care sports medicine FDs and fellowship faculty.

Assessment of Risk Factors:

Questions were designed to delineate factors [clinical experience, letters of recommendation (LOR), scholarship, service commitment, interview performance, etc] perceived to be associated with entry into PCSM fellowship (1-10 scale; 10 = highest value). Weighted mean ± SD were calculated for each question.

Main Outcome Measures:

Determination of most valued factors for entry into PCSM fellowship.

Results:

Responses were provided by 242/2332 (10.4%) of the American Medical Society for Sports Medicine members, including 77 of 175 (44%) FDs. The top 3 factors for entry into PCSM fellowships for all respondents were as follows: interview performance (9.17 ± 1.13), LOR from SM fellowship faculty (8.20 ± 1.67), and high school game/event coverage (7.83 ± 1.70). Musculoskeletal ultrasound experience (4.50 ± 2.23) and residency training in pediatrics (4.58 ± 2.54), internal medicine (4.48 ± 2.44), emergency medicine (4.44 ± 2.59), and physical medicine and rehabilitation (4.40 ± 2.83) received the lowest scores.

Conclusions:

Applicants seeking entry into SM fellowships should prioritize performance during interviews, LOR from SM fellowship faculty, and team game/event coverage experiences.
Mucosal-associated Lymphoid Tissue (MALT) Lymphoma in Association With Pediatric Primary Sjogren Syndrome: 2 Cases and Review
Authors: Tesher Melissa S. , Esteban Ysabella , Henderson Tara O. , Villanueva Gabriela , Onel Karen B.
Published: October 2018

Mucosal-associated lymphoid tissue (MALT) lymphoma is rare in the pediatric population, but primary Sjogren syndrome is a well-established risk factor for this malignancy. This report describes 2 cases of MALT lymphoma in children with Sjogren syndrome. A 15-year-old girl developed MALT lymphoma of the parotid gland as the presenting symptom of Sjogren syndrome. In the second case, a 15-year-old boy with known Sjogren syndrome presenting mainly with arthritis was diagnosed with MALT lymphoma, also of the parotid gland. With early diagnosis and treatment, outcomes in pediatric MALT lymphoma are generally encouraging. Pediatric oncology specialists should be aware of the association of MALT lymphoma with Sjogren syndrome and have a high index of suspicion for this malignant complication.
Personnel Management and Biosecurity of U.S. High-Level Isolation Units
Authors: Herstein Jocelyn J. , Biddinger Paul D. , Gibbs Shawn G. , Le Aurora B. , Jelden Katelyn C. , Hewlett Angela L. , Lowe John J.
Published: October 2018

OBJECTIVE

To describe strategies used by US high-level isolation units (HLIUs) to recruit, train, and sustain a full team of multidisciplinary staff and identify how units are secured.

BACKGROUND

Fifty-six US hospitals have been designated HLIUs, capable of providing safe care to patients with highly infectious disease.

METHODS

An electronic survey was administered to the 56 HLIUs in spring of 2016. Responses were collected via a fillable PDF and analyzed using descriptive statistics.

RESULTS

Thirty-six HLIUs (64%) responded; 33 completed surveys, and 3 reported no longer being a designated HLIU. HLIUs reported large numbers of multidisciplinary staff, primarily consisting of RNs and critical care clinicians. Nearly all HLIUs (94%) required orientation training, although hours varied.

CONCLUSIONS

Over a short period, HLIUs recruited and trained significant numbers of staff with little guidance. Costs of ongoing trainings are considerable, and it remains unclear how HLIUs will continue funding these activities.
Staff Perceptions of Decision-Making in a Shared Governance Culture
Authors: Di Fiore Tina , Zito Antoinette , Berardinelli Amy , Bena James F. , Morrison Shannon L. , Keck Diane E. , Kennedy Kathleen , Stibich Ann , Albert Nancy M.
Published: October 2018

OBJECTIVE

To evaluate differences in the shared decision-making perceptions of clinical nurses between initial implementation of a shared governance model and perceptions 3 years later after the model has matured.

BACKGROUND

Shared decision-making empowers nurses to have a voice in their practice and supports engagement and retention.

METHODS

A prospective, 2-group comparative design was conducted using the Index of Professional Nursing Governance, a validated, reliable tool. After comparing data univariately, a multivariable linear regression model was used to evaluate the impact of nurse characteristics on shared decision-making responses.

RESULTS

Mean overall shared decision-making score (P = .23) and domain scores (P values between .055 and .63) did not increase in 2015 compared with 2012. After adjusting for differences in nurse characteristics between groups, overall score (P = .017) and 3 of 6 domain scores improved: professional control of work, structures for decisions and access to information (all P values between .005 and .031).

CONCLUSION

As shared governance became established, shared decision-making scores increased.
Incivility Toward Nursing Students in Clinical Rotations
Authors: Tecza Bonnie M. , Boots Brenda K. , Mains Brandi C. , Dryer Lisa D. , Oertle Dena L. , Pontius Camie J. , Cantu Chelcia L. , Olney Adrienne , McElroy Susan , Teasley Susan
Published: October 2018

OBJECTIVE

The purpose of this study was to measure nursing student perceptions of incivility in the clinical learning environment and test interventions that improve these perceptions. The secondary aim was to further test the reliability of the Nursing Student Perception of Civil and Uncivil Behaviors (NSPCUB) tool.

BACKGROUND

Incidence of incivility in nursing is well documented in the literature; however, there are few evidence-based interventions to combat this phenomenon.

METHODS

NSPCUB was administered to 314 nursing students. Data were used to develop hospital-wide and unit-specific interventions. After implementation of the interventions, the survey was administered to 410 students.

RESULTS

There was a statistically significant mean increase for 7 of the 12 survey items, hospital-wide, and the findings reenforced NSPCUB as a highly reliable tool.

CONCLUSIONS

This instrument can be used by nurse executives to measure perceptions of incivility, identify areas for improvement, and implement interventions.
Dynamic of the somatosensory system in postherpetic neuralgia
Authors: Gierthmühlen Janne , Braig Olga , Rehm Stefanie , Hellriegel Jana , Binder Andreas , Baron Ralf
Published: October 2018

Introduction:

In postherpetic neuralgia (PHN) different types of patients can be distinguished regarding their predominant peripheral nociceptor function.

Objective:

The aim was to examine somatosensory profiles in the course of disease with special regard to the different subtypes existing in PHN.

Methods:

Twenty patients with PHN (7 men and 13 women, age 67 ± 9.6 years) were examined at baseline (disease duration 18.1 ± 26 months) and follow-up (31.6 ± 23.8 months later) with quantitative sensory testing (protocol of the German Research Network on Neuropathic Pain).

Results:

Fourteen (70%) PHN patients presented with impaired (iPHN) and 6 (30%) with preserved (pPHN) C-fiber function. Groups did not differ regarding age, disease duration, or pain intensity at baseline. Both groups did not differ regarding change in pain intensity (−0.5 ± 2.3 vs −1.7 ± 2.6 numerical rating scale, P = n.s.) at follow-up. Impaired PHN improved in thermal and mechanical detection thresholds as well as allodynia independent from change in pain intensity. By contrast, pPHN showed an increase in mechanical pain sensitivity (1.4 ± 2.5 vs −0.4 ± 2.2, P < 0.05) and a trend towards a stronger loss of detection (66% vs 33%, P = n.s.) on follow-up.

Conclusion:

Results demonstrate that patients with preserved C-fiber function are more predisposed to develop signs of central sensitization as demonstrated by an increased mechanical pain sensitivity. Impaired C-fiber function is able to improve even in chronic cases, but a functional loss is unlikely to play a role here. The knowledge of development of somatosensory profiles in the course of the disease offers possibilities to optimize a mechanism-based treatment.
NEO6860, modality-selective TRPV1 antagonist: a randomized, controlled, proof-of-concept trial in patients with osteoarthritis knee pain
Authors: Arsenault Pierre , Chiche Dan , Brown William , Miller Jeffrey , Treister Roi , Leff Richard , Walker Philippe , Katz Nathaniel
Published: October 2018

Introduction:

NEO6860 is a TRPV1 antagonist when activated by capsaicin but not by heat or pH, developed to relieve pain without the adverse events reported with non–modality-selective TRPV1 antagonists.

Objective:

The primary Objective of this study was to evaluate the analgesic efficacy and safety of NEO6860 after 1 day oral dosing in patients with Kellgren-Lawrence stage I, II or III osteoarthritis of the knee.

Method:

This randomized, double-blinded, 3-period crossover, phase II study compared 1 day (2 doses) of NEO6860 (500 mg twice a day), placebo, and naproxen in 54 patients with osteoarthritis knee pain. Primary endpoint was reduction in pain intensity (PI) on Numerical Rating Scale after exercise, using the staircase test, 8 hours after dose.

Results:

Level of PI, compared with baseline, was numerically lower during NEO6860 and naproxen periods vs placebo at 3 and 24 hours, but not at 8 hours after first dose. A statistically significant effect for naproxen and a trend for NEO6860 were observed at 3 and 24 hours. Least square means' (95% confidence interval) change in PI at 24 hours was −0.67 (−1.09 to −0.26), −0.97 (−1.39 to −0.55), −0.29 (−0.71 to 0.13) for NEO6860, naproxen, and placebo, respectively. NEO6860 exposure was ∼1.6 times higher compared with previous phase I. In this study, NEO6860 safety profile was less favorable than naproxen or placebo. Possibly NEO6860-related adverse events included: feel hot, headache, nausea, dizziness, fatigue, hypoaesthesia, and increased blood pressure.

Conclusion:

In this exploratory study, NEO6860 did not statistically significantly outperform placebo but showed an analgesic trend, without impacting body temperature and heat pain perception. Further studies are warranted to explore the potential of NEO6860 in other pain indications. We intent to optimize the dose and evaluate analgesic synergism with other mechanism.
Low-Level Laser Treatment Is Ineffective for Capsular Contracture: Results of the LaTCon Randomized Controlled Trial
Authors: Azimi Farhad , Flitcroft Kathy , Mathieu Erin , Karantonis Rebecca , Snook Kylie , Spillane Andrew J.
Published: October 2018

Background:

Breast reconstruction with implants can be complicated by symptomatic capsular contracture, especially after radiotherapy. A phase I, nonrandomized clinical trial demonstrated improvement in capsular contracture and avoidance of revision surgery with low-level laser therapy. This phase II, double-blind, randomized controlled trial assessed the efficacy of low-level laser for treating capsular contracture in women with breast reconstruction following mastectomy for breast cancer.

Methods:

Participants had completed their definitive implant-based reconstruction a minimum of 6 months previously and were randomized to weekly treatments over 6 weeks with either an active or inactive low-level laser handpiece (Riancorp LTU-904). Pain, tightness, arm movement, and appearance were assessed by patient questionnaires. Breast symmetry, shape, naturalness, softness, and grade of contracture were assessed by clinician reports. Participants were assessed at 1 and 6 months after completion of the treatments.

Results:

A total of 42 patients (intervention arm, n = 20; placebo, n = 22) were assessed in the trial. Thirty-two had postmastectomy radiotherapy. There was no significant difference in the change in any patient-reported outcomes or clinician-reported outcomes of breast symmetry, shape, or naturalness for the two groups. There was a significantly greater improvement in clinician-reported breast softness (p < 0.05) and degree of contracture (p < 0.05) in the placebo group at both 1- and 6-month follow-up.

Conclusion:

Low-level laser is not an effective therapy for breast implant capsular contracture in reconstruction patients.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, I.
Arthroscopic Ganglionectomy in the Pediatric Population
Authors: Ben-Amotz Oded , Pezeshk Ronnie A. , Sammer Douglas M. , Cheng Jonathan
Published: October 2018

Background:

Arthroscopic dorsal wrist ganglionectomy is an established alternative to open excision in the adult population. The purpose of this study was to retrospectively compare outcomes of arthroscopic and open dorsal wrist ganglionectomy in the pediatric population.

Methods:

All patients who underwent arthroscopic or open dorsal wrist ganglionectomy at a single pediatric institution between 2011 and 2014 were retrospectively evaluated by chart review and telephone interview. The primary outcome variable was whether or not the cyst had recurred. Other outcome measures included the incidence of complications, and patient-rated outcome measures such as satisfaction, pain, function, and aesthetics.

Results:

There were eight cases of arthroscopic and 19 cases of open ganglionectomy, with a mean age of 14 years. At an average follow-up of 2 years, the recurrence rate was one of eight for the arthroscopic group and two of 19 for the open group. No patients in the arthroscopic group reported functional limitations, compared with three patients in the open group. On a 10-point scar appearance scale, with 1 being not satisfied at all and 10 being highly satisfied, the median score in the arthroscopic group was 9.5, compared with 8 in the open group. No patients in the arthroscopic group had residual pain at the surgical site, compared with nine patients in the open group, a finding that was statistically significant. All patients in the arthroscopic group reported that they would undergo surgery again, whereas two patients in the open group would not undergo surgery again.

Conclusion:

Arthroscopic dorsal wrist ganglionectomy compares favorably with open ganglionectomy in the pediatric population.
Vascularized Composite Allotransplantation: Alternatives and Catch-22s
Authors: Diaz-Siso J. Rodrigo , Borab Zachary M. , Plana Natalie M. , Parent Brendan , Stranix John T. , Rodriguez Eduardo D.
Published: October 2018

Technical success has been achieved in several forms of vascularized composite allotransplantation, including hand, face, penis, and lower extremity. However, the risks of lifelong immunosuppression have limited these procedures to a select group of patients for whom nontransplant alternatives have resulted in unsatisfactory outcomes. Recent reports of facial allograft failure, and subsequent reconstruction using autologous tissues, have reinforced the idea that a surgical contingency plan must be in place in case this devastating complication occurs. Interestingly, backup plans in the setting of vascularized composite allotransplantation consist of the nontransplant alternatives that were deemed suboptimal in the first place. Moreover, these options may have been exhausted before transplantation, and may therefore be limited in the case of allograft loss or reamputation. In this article, the authors describe the surgical and nonsurgical alternatives to hand, face, penis, and lower extremity transplantation. In addition, the authors explore the ethical implications of approaching vascularized composite allotransplantation as a “last resort” or as a “high-risk, improved-outcome” procedure, focusing on whether nontransplant options eventually preclude vascularized composite allotransplantation, or whether vascularized composite allotransplantation limits future nontransplant reconstruction.
Alar Cinching with Subcutaneous Flaps: A Procedure to Achieve Narrowing of the Nasal Base while Controlling the Alar Axis and Sidewall Curvature
Authors: Hirohi Toshitsugu , Ng Donald , Nagai Koji , Yoshimura Kotaro
Published: October 2018

Background:

Insufficient narrowing of alar width, alar distortion, and noticeable scarring are commonly encountered after alar base reduction. The authors aimed to demonstrate an alar cinching with subcutaneous flaps procedure to reduce the alar width while controlling the alar axis and sidewall curvature.

Methods:

A retrospective chart review of 560 patients who underwent alar base reduction between 2000 and 2015 was performed. The clinical outcomes of alar cinching with subcutaneous flaps were compared to those of vestibular floor excision with cinching suture. Mean change in alar width was compared to assess narrowing efficacy between the two groups. In addition, mean changes in interalar distance for the upper, middle, and lower parts of the alae were compared to evaluate the alteration of alar axes.

Results:

Seventy-three patients who underwent alar base narrowing alone (alar cinching with subcutaneous flaps,n= 42; vestibular floor excision with cinching suture,n= 31) were identified. Alar cinching with subcutaneous flaps was significantly more effective than vestibular floor excision with cinching suture in reducing alar width. In patients with vertical alar axes, alar cinching with subcutaneous flaps achieved more uniform narrowing of the entire alae, resulting in prevention of alar distortion. The incidence of complications after alar cinching with subcutaneous flaps was 5.7 percent.

Conclusions:

Alar cinching with subcutaneous flaps achieved sufficient narrowing of the nasal base in the long-term follow-up in patients with any type of alar axis and enabled the reduction of sidewall curvature while eliminating the need for wedge resection.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, III.
A 26-Year Experience with Microsurgical Reconstruction of Hemifacial Atrophy and Linear Scleroderma
Authors: Chen Jenny T. , Schmid Daniel B. , Israel Jacqueline S. , Siebert John W.
Published: October 2018

Background:

Parry Romberg disease (hemifacial atrophy) and linear scleroderma (coup de sabre) are progressive, usually unilateral facial atrophies of unknown cause. The gold standard treatment for these patients has been microsurgical reconstruction following the “burning out” of the facial atrophy and stable contour for 2 years.

Methods:

The authors report their experience treating patients with hemifacial atrophy and linear scleroderma with free tissue transfers between 1989 and 2016. A modified parascapular flap based on the circumflex scapular artery was most commonly used.

Results:

A total of 177 patients were included. The most common complication was hematoma, occurring in 12 patients (7 percent). Follow-up ranged from 1 to 26 years. All patients subjectively experienced improved facial symmetry and aesthetics. No disease process has recurred to date, even in cases of severe, progressive disease.

Conclusions:

In the authors’ experience, patients treated early in their disease course have immediate and sustained correction of their deformity, with slowing or in most cases cessation of the disease process following free tissue transfer. The authors now advocate for immediate reconstruction for active disease, especially in young children.

CLINICAL QUESTIONS/LEVEL OF EVIDENCE:

Therapeutic, IV.
Inflammation Relates to Poorer Complex Motor Performance Among Adults Living With HIV on Suppressive Antiretroviral Therapy
Authors: Montoya Jessica L. , Campbell Laura M. , Paolillo Emily W. , Ellis Ronald J. , Letendre Scott L. , Jeste Dilip V. , Moore David J.
Published: October 2018

Background:

Inflammatory processes have been suggested to underlie early neurologic abnormalities among persons living with HIV (HIV-positive), such as deficits in complex motor function, that are purported to remit with effective antiretroviral therapy (ART). We hypothesized that HIV will have negative direct and indirect effects through inflammation on complex motor performance.

Methods:

The sample consisted of 90 ART-treated virally suppressed HIV-positive and 94 HIV-negative adults, aged 36–65 years, with balanced recruiting in each age decade (36–45, 46–55, and 56–65). Biomarkers of inflammation (d-dimer, IL-6, MCP-1/CCL2, sCD14, and TNF-α) were measured, and a composite inflammation burden score was calculated. Complex motor performance was evaluated using the Grooved Pegboard Test.

Results:

The HIV-positive group had worse complex motor performance (P = 0.001; Hedges g = −0.49) and a higher average inflammation burden composite score (P < 0.001; Hedges g = 0.78) than the HIV-negative group. Path analyses indicated that the indirect effect of HIV disease on complex motor performance through inflammation burden was statistically significant, accounting for 15.1% of the effect of HIV on complex motor performance.

Conclusions:

Although neurologic findings (eg, deficits in motor speed/dexterity) commonly associated with HIV infection typically remit with ART, our analysis indicates that inflammation plays an important role in worse complex motor skills among HIV-positive adults. Future studies of strategies for managing chronic inflammation in HIV should consider using an inflammation burden composite and examining its effect on complex motor performance.
Vaginal Jade Eggs: Ancient Chinese Practice or Modern Marketing Myth?
Authors: Gunter Jennifer , Parcak Sarah
Published: October 2018

Objective

To identify evidence that vaginal jade eggs were recommended or used in sexual health practices or for pelvic muscle exercises in ancient Chinese culture.

Materials and Methods

A search of the online databases of 4 major Chinese art and archeology collections in the United States.

Results

More than 5000 jade objects were viewable in online databases. No vaginal jade eggs were identified.

Conclusions

No evidence was found to support the claim that vaginal jade eggs were used for any indication in ancient Chinese culture.
Genetic distance between complex repeats
Authors: Ferretti Luca , Ruiz-Herrera Aurora , Ledda Alice
Published: October 2018

Complex nucleotide or aminoacid repeats with long units play an important role in proteins. The evolutionary analysis of these variants is challenging due to genetic diversity within repeat units as well as variability in the arrangement of different units along the repeat sequence. Here we present a new approach for the computation of genetic distances between complex repeats. This method takes into account evolutionary processes including point mutations, insertions and deletions of repeat units, as well as duplication of single units. We provide an algorithm for the computation of these distances along with the corresponding global pairwise alignment of repeats. As an example, we apply our approach to the evolution of repeat units in the highly polymorphic zinc-finger repeat domain of the PRDM9 protein across wild populations of house mice. This approach opens the way for new insights into the evolutionary history of polymorphic repeats.
One and Two Year Visual Outcomes from the Moorfields AMD Database - an Open Science Resource for the Study of Neovascular Age-related Macular Degeneration
Authors: Fasler Katrin , Moraes Gabriella , Wagner Siegfried K. , Kortuem Karsten U. , Chopra Reena , Faes Livia , Preston Gabriella , Pontikos Nikolas , Fu Dun Jack , Patel Praveen J. , Tufail Adnan , Lee Aaron Y. , Balaskas Konstantinos , Keane Pearse A.
Published: October 2018

Objectives

To analyse treatment outcomes and share clinical data from a large, single-center, well-curated database (8174 eyes / 6664 patients with 120,756 single entries) of patients with neovascular age related macular degeneration (AMD) treated with anti-vascular endothelial growth factor (VEGF). By making our depersonalised raw data openly available, we aim to stimulate further research in AMD, as well as setting a precedent for future work in this area.

Setting

Retrospective, comparative, non-randomised electronic medical record (EMR) database cohort study of the UK Moorfields AMD database with data extracted between 2008 and 2018.

Participants

3357 eyes/patients (61% female). Extraction criteria were ≥ 1 ranibizumab or aflibercept injection, entry of “AMD” in the diagnosis field of the EMR, and a minimum of one year of follow-up. Exclusion criteria were unknown date of first injection and treatment outside of routine clinical care at Moorfields before the first recorded injection in the database.

Main outcome measures

Primary outcome measure was change in VA at one and two years from baseline as measured in Early Treatment Diabetic Retinopathy Study (ETDRS) letters. Secondary outcomes were the number of injections and predictive factors for VA gain.

Results

Mean VA gain at one-year and two years were +5.5±0.5 and +4.9±0.68 letters respectively. Fifty-four percent of eyes gained ≥5 letters at two years, 63% had stable VA (±≤14 letters), forty-four percent of eyes maintained good VA (≥70 letters). Patients received a mean of 7.7±0.06 injections during year one and 13.0±0.2 injections over two years.

Younger age, lower baseline VA, and more injections were associated with higher VA gain at two years.

Conclusion

This study benchmarks high quality EMR study results of real life AMD treatment and promotes open science in clinical AMD research by making the underlying data publicly available.

Strengths and limitations of this study

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Large sample size, retrospective, single centre, electronic medical record database study

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High quality real life data

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Open science approach with sharing of depersonalised raw data
Long Range Order and Short Range Disorder in Saccharomyces cerevisiae Biofilm
Authors: Piras Vincent , Chiow Adam , Selvarajoo Kumar
Published: October 2018

Biofilm, a colony forming cooperative response of microorganisms under environmental stress, is a major concern for food safety, water safety and drug resistance. Most current works focus on controlling biofilm growth by targeting single genes. Here, we investigated transcriptome-wide expressions of the biofilm yeast Saccharomyces cerevisiae in wildtype, and 6 previously identified biofilm regulating overexpression strains (DIG1, SAN1, TOS8, ROF1, SFL1, HEK2). When tested across various statistical distributions, all transcriptome-wide data fitted well with lognormal distribution above TPM value of 5. Using this threshold as a low expression filter, Pearson auto-and cross-correlation reveal a strong transcriptome-wide invariance among all genotypes, which is also reflected by the random selection of 50 gene expressions. Focusing on the 50 highly expressed genes, however, they differ significantly between the genotypes. Principal components analysis (PCA) shows global similarity between DIG1, SAN1, ROF1, SFL1 and HEK2. Thus, although single overexpression strains may show significant favourable local and acute expression changes (short range disorder), the almost unperturbed global and collective structure between the genotypes indicate gradual adaptive response converging to original stable biofilm states (long range order). Hierarchical clustering and Gene Ontology show 11 groups of local (e.g. mitochondria processes, amine & nucleotide metabolic processes) and 6 groups of global (e.g. transcription, translation & cell cycle) processes for all genotypes. These data indicate that there is a strong global regulatory structure that keeps the overall biofilm stable in all investigated strains.