bluuebunny/crossref_metadata_2025 huggingface dataset:
Incidence, Persistence, Clearance, and Correlates of Genital Human Papillomavirus Infection and Anogenital Warts in a Cohort of Men Living With Human Immunodeficiency Virus in South Africa
Authors: Chikandiwa Admire , Pisa Pedro T. , Muller Etienne E. , Tamalet Catherine , Mayaud Philippe , Chersich Matthew F. , Delany-Moretlwe Sinead
Published: February 2019

Objective

To estimate the incidence; persistence and correlates of human papillomavirus (HPV) infection and anogenital warts (AGW) among men living with human immunodeficiency virus (MLHIV).

Methods

Overall, 304 MLHIV 18 years or older were enrolled and attended follow-up visits at 6, 12, and 18 months. Clinicians examined for AGW, collected blood, and penile swabs for HPV testing (Roche Linear Array) at each visit. Time to AGW incidence or clearance was estimated by Kaplan-Meier method. Factors associated with persistent HPV infection and AGW clearance were evaluated with generalized estimating equations and Cox regression, respectively.

Results

Mean age of participants was 38 years (standard deviation, 8 years); 25% reported more than 1 sexual partner in the past 3 months. Most (65%) participants were on antiretroviral treatment (ART) with a median CD4+count of 445 cells/μL (interquartile range, 328–567). Prevalence of HPV infection and AGW at enrolment were 79% (224 of 283) and 12% (36 of 304), respectively. Two hundred fifty-nine men were followed up for a median (interquartile range) 1.4 years (0.5–1.7 years). Incidence of any-genital HPV infection was 2.9 (95% confidence interval, 1.5–5.5) per 100 person-years. Persistence of any-genital HPV infection was 35% (68 of 192) and was higher among MLHIV with low CD4+count (adjusted odds ratio, 3.54; 95% confidence interval, 2.07–6.05). Incidence of AGW was 1.4 per 100 person-years. Men living with human immunodeficiency virus with high CD4+count were more likely to clear AGW than those with low CD4 count (adjusted hazard ratio, 3.69; 95% confidence interval, 1.44–9.47). No associations were observed between persistent genital HPV infection, AGW clearance with enrolment ART status or duration.

Conclusions

Human immunodeficiency virus–positive men have a high burden of genital HPV infection and AGW. The ART and HPV vaccine could reduce this burden.
The Prevalence of Mycoplasma genitalium and Association With Human Immunodeficiency Virus Infection in Symptomatic Patients, Johannesburg, South Africa, 2007–2014
Authors: Mahlangu Mahlape P. , Müller Etienne E. , Venter Johanna M.E. , Maseko Dumisile V. , Kularatne Ranmini S.
Published: February 2019

Background

Mycoplasma genitalium is associated with genital discharge syndrome, but limited prevalence data are available in South Africa. The prevalence rates of M. genitalium infection and human immunodeficiency virus (HIV) coinfection were determined in urogenital specimens collected from male and female patients presenting with genital discharge syndrome to a primary health care center in Johannesburg, South Africa from 2007 through 2014.

Methods

Genital specimens from 4731 patients were tested by a validated in-house multiplex real-time polymerase chain reaction assay for the detection of Neisseria gonorrhoeae, Chlamydia trachomatis, Trichomonas vaginalis, and M. genitalium. Sera were tested for HIV infection using the Determine HIV 1/2 and Unigold assays.

Results

The relative prevalence of M. genitalium in males and females was 8.9% and 10.6%, respectively. The prevalence of HIV infection in those infected with M. genitalium, without other sexually transmitted infections (STIs), was significantly higher than in those without M. genitalium infection (48.9% vs. 40.5%, P = 0.014). This significant difference in HIV seroprevalence was particularly observed among females in the study cohort.

Conclusions

The relative prevalence of M. genitalium and its association with prevalent HIV among females with vaginal discharge syndrome (VDS) calls for further research on the potential role of M. genitalium in the transmission and acquisition of HIV.
Who Has Yet to Test? A Risk Score for Predicting Never Having Tested for Human Immunodeficiency Virus Among Women and Men in Rural Malawi
Authors: Harrington Bryna J. , Turner Abigail Norris , Chemey Elly , Esber Allahna , Kwiek Jesse , Norris Alison H.
Published: February 2019

Background

Human immunodeficiency virus (HIV) status awareness is important for preventing onward HIV transmission, and is one of the Joint United Nations Programme on HIV and AIDS (UNAIDS) 90-90-90 goals. Efforts to scale up HIV testing have generally been successful, but identifying at-risk individuals who have never tested for HIV—a population necessary to reach improved HIV status awareness—remains challenging.

Methods

Using data from a community-based cohort of people living in rural central Malawi, we identified demographic, socioeconomic, and sexual health correlates of never having tested for HIV. Correlates were assigned values from the logistic regression model to develop a risk score that identified who had never tested for HIV.

Results

Among 1310 ever sexually active participants, 7% of the women and 13% of the men had never tested for HIV. Of those who had tested for HIV, about 30% had tested more than 12 months ago. For women, younger age and poorer sexual health knowledge were correlated with never having tested for HIV, and the c-statistic for the risk score was 0.83. For men, their partner having not tested for HIV, low socioeconomic status, and poor sexual health knowledge were correlated with never testing for HIV (c-statistic, 0.81). Among those with a score of 3 or greater, the sensitivity and specificity for never having tested for HIV were 81% and 77% for women, and 82% and 66% for men, respectively.

Conclusions

About 10% of participants had never tested for HIV. This risk score could help health professionals to identify never testers to increase HIV status awareness in line with 90-90-90 goals.
Case Report: Delayed Vitamin A Retinopathy Secondary to Bariatric Surgery
Authors: Bhakhri Raman , Ridder William H. , Adrean Sean
Published: February 2019

SIGNIFICANCE

Although rare, vitamin A retinopathy should be considered by the clinicians in their differentials for conditions that can lead to nyctalopia, especially in those patients who have undergone bariatric surgery. Patients must be educated on this potential delayed adverse effect of the surgery and possible lifelong vitamin A supplementation.

PURPOSE

The purpose of this study was to report a rare case of delayed vitamin A retinopathy that occurred because of vitamin A malabsorption secondary to bariatric surgery.

CASE REPORT

A 55-year-old woman presented with nyctalopia and dark adaptation problems. The patient had a history of gastric bypass surgery 22 years earlier. Fundus examination revealed a large number of small white dots in the midperiphery of both eyes. Electrophysiology testing revealed flat-lined scotopic responses. Vitamin A levels were found to be severely reduced. Subsequent vitamin A supplementation resulted in the reversal of all signs and symptoms.

CONCLUSIONS

This case report demonstrates the importance of considering vitamin A deficiency in patients who present with symptoms of nyctalopia with a history of bariatric surgery. Clinicians should be aware of a possible delayed onset and refer for appropriate testing and treatment, as vitamin A retinopathy has been shown to be reversible. Because other conditions can present with nyctalopia and retinal white spots, clinicians also need to consider the appropriate differential diagnoses. Lifelong monitoring is indicated because reoccurrences have been reported.
Reasons for Laser in Situ Keratomileusis in China: A Qualitative Study
Authors: Xu Yanjiao , Li Shunping , Gao Zhongchun , Nicholas Stephen
Published: February 2019

SIGNIFICANCE

Myopia is a major health issue in East Asian countries, especially in China. By identifying Chinese patients' motivations for laser in situ keratomileusis (LASIK) surgery, our results are expected to help clinicians counsel patients before LASIK surgery and to maximize patients' post-operative LASIK surgery satisfaction, improving the quality of LASIK surgery services.

PURPOSE

Laser in situ keratomileusis has become a popular type of refractive surgery for the correction of myopia worldwide. This study uses qualitative inquiry approaches to understand the motives and processes of patients' LASIK surgery decision making.

METHODS

A purposive sample of 45 patients who had decided to undergo LASIK was recruited. Our qualitative study used in-depth interviews and used content analysis to interpret the data.

RESULTS

Among 45 participants, 48.9% reported that career requirements were the most important reason for seeking LASIK surgery. The inconvenience of wearing glasses or lenses during activities of daily life was also a primary motive. Improving facial appearance was a main reason for female but not male respondents. Potential complications of spectacles and contact lenses in addition to maturation of LASIK technology were also reported motives to seek surgery. Participants gave multiple, overlapping reasons for LASIK surgery.

CONCLUSIONS

These findings suggest that motives to seek LASIK surgery are not only a desire to correct refractive error but also social factors and confidence in improved surgical technology. The implications for clinicians are to be aware of these multiple motives for LASIK to improve the quality and effectiveness of health services for myopia patients.
Unilateral Strength Training and Mirror Therapy in Patients With Chronic Stroke
Authors: Ehrensberger Monika , Simpson Daniel , Broderick Patrick , Blake Catherine , Horgan Frances , Hickey Paula , O'Reilly Joanne , Monaghan Kenneth
Published: February 2019

Objective

The aim of the study was to investigate the feasibility and potential effectiveness of mirror-aided cross-education compared with cross-education alone in poststroke upper limb recovery.

Design

A pilot randomized controlled parallel group study was carried out. Thirty-two patients with chronic stroke followed a 4-wk isometric strength training program performed with the less-affected upper limb three times per week. Participants in the mirror and strength training group observed the reflection of the exercising arm in the mirror. Participants in the strength training only group exercised without a mirror entirely. Participant compliance, adverse effects, and suitability of outcome measures assessed feasibility. Effectiveness outcomes included maximal isometric strength measured with the Biodex Dynamometer, the Modified Ashworth Scale, and the Chedoke Arm and Hand Activity Inventory.

Results

Compliance was high with no adverse effects. The use of the Biodex Dynamometer must be reviewed. Mirror therapy did not augment the cross-education effect (P > 0.05) in patients with chronic stroke when training isometrically.

Conclusions

This pilot trial established the feasibility of a randomized controlled trial comparing mirror-aided cross-education with cross-education alone for poststroke upper limb recovery. Mirror therapy did not augment cross-education when training isometrically. However, results indicate that the combination of interventions should be investigated further applying an altered training protocol.
Organizing a Multidisciplinary Research Team: Strategies, Execution, and Outcomes
Authors: Sterbenz Jennifer M. , Nasser Jacob S. , Chung Kevin C.
Published: February 2019

Maintaining a competitive edge is increasingly imperative for surgical research teams. To publish as efficiently and effectively as possible, research teams should apply business strategies and theories in everyday practice. Drawing from concrete examples in both the corporate and nonprofit worlds, and by reflecting on the practices of the Michigan Comprehensive Hand Center for Innovation Research, this article identifies important business theories that can be applied to plastic surgery research. These theories can potentially be applied in practice and include (1) development of a realistic vision and strategies, (2) effective execution of these strategies, and (3) reflective evaluation for continual improvement.
Getting the Best Results in Abdominoplasty: Current Advanced Concepts
Authors: Boudreault David J. , Sieber David A.
Published: February 2019

Learning Objectives:

After studying this article and viewing the videos, the participant should be able to: 1. Describe the safe techniques recommended for patients undergoing a lipoabdominoplasty. 2. Demonstrate safe planning techniques for marking a patient for a lipoabdominoplasty. 3. Summarize the various techniques for performing rectus plication. 4. State the current understanding of chemoprophylaxis for outpatient surgical patients. 5. Determine the appropriate placement and shape of the ideal umbilicus.

Abdominoplasty and lipoabdominoplasty surgery is one of the core procedures performed by plastic surgeons in the United States. As with most plastic surgery, it is part art and part science. In this article, the authors try to summarize the science behind this procedure, and point to the generally accepted artistic aspects that are currently still under debate. As this procedure has one of the highest morbidity and mortality rates in the specialty, the authors have also reviewed safe practices.
Complementary Fat Graft Retention Rates Are Superior to Initial Rates in Craniofacial Contour Reconstruction
Authors: Denadai Rafael , Raposo-Amaral Cesar Augusto , da Silva Simone Alves , Buzzo Celso Luiz , Raposo-Amaral Cassio Eduardo
Published: February 2019

Background:

The purposes of this study were to (1) assess complementary fat graft outcomes, (2) compare initial and complementary fat graft retention rates, and (3) evaluate the influence of different postoperative time points (3, 6, and 12 months after the initial procedure) for performing complementary fat grafting on fat graft outcomes.

Methods:

A prospective analysis was conducted on patients with unilateral craniofacial contour deformities (n = 115) who underwent initial and complementary fat grafting. Complementary fat grafting was performed 3, 6, or 12 months after the initial fat grafts. Standardized ultrasonographic craniofacial soft-tissue thickness measurements were performed blindly to determine the initial and complementary fat graft retention rates at 1, 3, 6, and 12 months after surgery.

Results:

A significant (p < 0.05) reduction of fat graft retention was observed within the first 3 postoperative months, and a maintenance of retention (p > 0.05) was observed at 3 through 12 months after surgery for both initial and complementary procedures. No significant (p > 0.05) differences were observed in comparative analysis of the postoperative time points. Complementary retention rates were significantly (p < 0.05) superior to initial retention rates at 3, 6, and 12 months after surgery. Complementary retention rates at 3, 6, and 12 months after surgery were significantly (p < 0.05) superior to initial retention rates for patients aged 18 years or older, those with Parry-Romberg syndrome, those who had undergone previous craniofacial bone surgery, and those with a recipient site at the forehead unit.

Conclusion:

The complementary fat graft retention rates were superior to the initial retention rates, with no significant differences among the postoperative time points for performing complementary procedures.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, II.
Achieving Reliable Diagnosis in Late Breast Implant Seromas: From Reactive to Anaplastic Large Cell Lymphoma
Authors: Di Napoli Arianna
Published: February 2019

Late onset of fluid collection surrounding breast implants may represent a serious issue when considering the possibility of breast implant–associated anaplastic large cell lymphoma, a newly recognized type of T-cell malignancy. However, many other factors, including trauma and infections, may be implicated in the formation of non-neoplastic periprosthetic delayed effusions. An appropriate management of late seromas, consisting of ultrasound-guided fluid drainage, cultures, cytology, and immunocytochemical and T-cell clonality studies, should be performed to achieve a correct and prompt diagnosis of breast implant–associated anaplastic large cell lymphoma. Criticisms in the diagnosis of late peri-implant effusions are here discussed in detail.
Characteristics and Treatment of Advanced Breast Implant–Associated Anaplastic Large Cell Lymphoma
Authors: Collins Meredith S. , Miranda Roberto N. , Medeiros L. Jeffrey , Silva de Meneses Marcelo Pinheiro , Iyer Swaminathan P. , Butler Charles E. , Liu Jun , Clemens Mark W.
Published: February 2019

Background:

Breast implant–associated anaplastic large cell lymphoma (BIA-ALCL) most commonly follows an indolent course; however, a subset of patients display more advanced disease marked by recurrent and disseminated growth refractory to treatment. This study evaluated outcomes of advanced disease, specifically bilateral disease, lymph node involvement, organ metastasis, and/or disease-related death.

Methods:

Published cases of BIA-ALCL from 1997 to 2018 and unpublished cases at the authors’ institution were retrospectively reviewed, and patients with advanced disease were selected. Treatment and outcomes were compared against a control of BIA-ALCL subjects without advanced disease.

Results:

Thirty-nine patients with advanced BIA-ALCL were identified who had bilateral disease (n = 7), lymph node and organ metastasis (stage IIB-IV, n = 24), and disease-related death (n = 8). Sixty-five patients were included in a comparison control group (stage 1A-1C). Treatment types for advanced disease patients were complete surgery, n = 16 (55.2%); limited surgery, n = 19 (65.5%); chemotherapy, n = 26 (89.7%); salvage chemotherapy, n = 11 (37.9%); radiation, n = 15 (51.7%); and autologous stem cell transplant, n = 6 (20.7%). The rates of complete remission for the bilateral and lymphadenopathy groups were 4 of 7 (57%, P < 0.001) and 16 of 24 (67%, P = 0.128), respectively. Compared with the control group, advanced disease patients had significantly longer time from diagnosis to definitive surgery (21 versus 8 months, P = 0.039) and a lower rate of complete surgery (59% versus 88%, P = 0.004).

Conclusions:

Advanced disease BIA-ALCL may be a consequence of a delay or suboptimal treatment of BIA-ALCL. Optimal adjuvant chemotherapy and indications for radiation for BIA-ALCL patients with advanced features are not yet clearly defined. Advanced disease is the end of the spectrum of cancer stages, and these patients substantiate the World Health Organization classification of BIA-ALCL as a lymphoma rather than benign or lymphoproliferative.
Breast Implant Illness: A Way Forward
Authors: Magnusson Mark R. , Cooter Rod D. , Rakhorst Hinne , McGuire Patricia A. , Adams William P. , Deva Anand K.
Published: February 2019

The link between breast implants and systemic disease has been reported since the 1960s. Although many studies have looked at either supporting or refuting its existence, the issue still persists and has now been labeled “breast implant illness.” The rise of patient advocacy and communication through social media has led to an increasing number of presentations to plastic surgeons. This article summarizes the history of breast implants and systemic disease, critically analyzes the literature (and any associated deficiencies), and suggests a way forward through systematic scientific study.
Two Distinct Immune Pathways Linking Social Relationships With Health: Inflammatory and Antiviral Processes
Authors: Leschak Carrianne J. , Eisenberger Naomi I.
Published: February 2019

Objective

Social relationships can both influence and be influenced by immune processes. Past work implicates two distinct pathways along which this interaction may occur: inflammatory processes and antiviral processes. This article reviews how social behavior is modulated by these two immune processes and how such processes may in turn regulate social behavior.

Methods

This narrative review outlines existing work on social behavior and both inflammatory and antiviral processes. We propose an evolutionary framework that aims to integrate these findings. Specifically, social isolation has evolutionarily increased the likelihood of wounding and therefore increased the need for inflammation, which works to promote healing. Conversely, broader social networks provide protection from physical threats but also lead to increased pathogen exposure, necessitating a more robust antiviral response.

Results

This review highlights that social adversity, such as social exclusion or loneliness, is associated with increased inflammation, whereas social contact is associated with increased antiviral immunity. Furthermore, increased inflammation leads to sensitivity to social stimuli, presumably to avoid hostile conspecifics and approach allies who may provide care while vulnerable. Individuals with inadequate antiviral immunity engage in behaviors that minimize pathogen exposure, such as reduced affiliative behavior.

Conclusions

This review suggests that adverse social experiences (social isolation, perceived social threat) may induce inflammatory responses while suppressing antiviral immunity, whereas positive experiences of social connection may reduce inflammation and bolster antiviral responses. Although acutely elevated inflammation would be adaptive under conditions where wounding is likely, chronic inflammation related to continued social adversity may have detrimental health consequences.
Lesser Known Facts of Small Cell Lung Cancer
Authors: Li Xin , Enzerra Michael , Smith Daniel Arnold , Rahnemai-Azar Amir Ata , Kikano Elias , Ramaiya Nikhil H.
Published: February 2019

Until recently, the treatment of small cell lung cancer (SCLC), a malignancy classically described as having a robust response to first-line therapy with near-universal recurrence, has remained relatively unchanged. Advancements in the management of SCLC have lagged behind those seen for non–small cell lung cancers. As the era of precision medicine and targeted immunotherapy evolves, radiologists must be familiar with the modern treatment paradigms of SCLC and associated imaging patterns, including classic and nonclassic appearances of treatment complications.
Postmortem Computed Tomography and Computed Tomography Angiography
Authors: Lee Heon , Lee Sookyoung , Cha Jang Gyu , Baek Taehwa , Yang Kyung-moo
Published: February 2019

With the introduction of modern imaging technology into the forensic field, postmortem imaging, particularly postmortem computed tomography (PMCT), has gained increasing importance in forensic investigations of deaths. In recent years, PMCT, which aims to provide observer-independent, reproducible forensic assessment in a minimally invasive manner, has been incorporated into routine forensic practice in many medicolegal institutions worldwide as a complement to autopsy. To address questions with regard to vascular pathologies, postmortem computed tomography angiography (PMCTA) has been developed and has become a useful tool for exploring the vascular system. Currently, these techniques play roles in screening for potential pathologies for later autopsy confirmation, facilitating focused dissection of the target area, and visualizing lesions that would be difficult or impossible to detect during autopsy. Adequate image interpretation requires knowledge and understanding of postmortem changes in the body and artefacts related to PMCT and PMCTA. This article reviews the PMCT and PMCTA techniques in terms of their indications, applications, advantages, and limitations for cardiothoracic applications. Our findings will enhance readers’ understanding of emerging CT techniques in forensic radiology.
Using Mirror Patients to Enhance Patient Safety
Authors: Harwayne-Gidansky Ilana , Culver Kathleen , Cavanaugh Sean , Panesar Rahul
Published: February 2019

Summary Statement

Unannounced, in situ simulations offer opportunities for interprofessional teams to train for pediatric emergencies and uncover latent safety threats (LST). Simulation fidelity is an important component of in situ simulations. Threats to fidelity include creating a fictional patient vignette, which limits realism and the opportunity for patient handoffs. The “mirror patient” model may enhance in situ simulation fidelity by using actual patient profiles, thereby removing vignettes and allowing for handoffs. This model may also aid in discovering LSTs. The mirror patient was positively received by participants, who reported realistic and useful simulation experience that provided a safe and supportive learning environment. Uncovering, recording, and reviewing LSTs into an institutional safety event reporting system allowed for tracking and accountability, including process improvement, equipment changes, and provider training without risk to any real patient. This model may further improve means to enhance hospital patient safety.
Exploring the Influence of Language on Assessment Given a Mismatch Between Language of Instruction and Language of Practice
Authors: Diab Mohammad I. , Nasr Ziad G. , El-Hajj Maguy S. , Elewa Hazem , El-Geed Hager A. , Wilby Kyle John
Published: February 2019

Summary Statement

A phenomenon is occurring in international settings where the language of program delivery and assessment does not match the primary language of practice. It is unknown whether determining competence in English disadvantages students for practice in non-English settings. As such, we conducted a pilot study to determine student performance and perceptions after completion of two Objective Structured Clinical Examinations (OSCEs) examinations, one conducted in English and one conducted in Arabic within an Arabic-speaking Middle Eastern setting. Twenty-two students completed both OSCEs. Overall scores were similar but student rankings differed. Students were more confident performing in Arabic, felt that the Arabic examination was more reflective of practice, and believed that use of Arabic OSCEs can promote better patient care. Findings support the notion that student success may be influenced by language of assessment and that we may need to rethink how we determine assessment validity in these emerging international education settings.
Short-term Results After Totally Robotic Restorative Total Proctocolectomy With Ileal Pouch Anal Anastomosis for Ulcerative Colitis
Authors: Hamzaoglu Ismail , Baca Bilgi , Esen Eren , Aytac Erman , Ozben Volkan , Aghayeva Afag , Bilgin Ismail A. , Karahasanoglu Tayfun
Published: February 2019

In this study, we aimed to present our initial experience on totally robotic total restorative proctocolectomy in ulcerative colitis (UC) patients. Patients undergoing a totally robotic restorative total proctocolectomy with ileal J-pouch anal anastomosis for UC between January 2015 and November 2017 were included. The da Vinci Xi was used for the operations. Patient demographics, perioperative and short-term operative outcomes were evaluated. Ten patients were included. The median operative time was 380 minutes(range, 300 to 480 min). The median blood loss was 65 mL (range, 5 to 400 mL). No conversion to open surgery was needed. The median time to flatus was 1 day (range, 1 to 2) and length of stay was 6 (4 to 12) days. Short-term complications (≤30 d) were superficial wound infection (n=3), anal bleeding (n=1), pouchitis (n=1). No mortality was observed during the study period. Our study, which is the largest series so far, reveals that totally robotic restorative proctocolectomy is a safe and feasible option for the surgical treatment of UC.
Preprocedural Administration of Simethicone and Otilonium Bromide Improves the Quality of Endoscopic Retrograde Cholangiopancreatography: A Prospective Randomized Trial
Authors: Somuncu Erkan , Sarici İnanc S. , Caliskan Yahya K. , Kalayci Mustafa U.
Published: February 2019

Purpose:

Endoscopic retrograde cholangiopancreaticography (ERCP) is performed for diagnostic and therapeutic purposes in patients with pancreaticobiliary diseases. We investigated the role of simethicone and concomitant otilonium bromide during ERCP.

Patients and Methods:

This prospective randomized study included 120 patients who underwent ERCP (study and control group=60 patients each). The study group received otilonium bromide and simethicone. The control group received no medication.

Results:

The quantity of duodenal foam and bubbles in the study group was significantly lesser than that in the control group. The duodenal motility score was 2.1±0.7 and 4.3±0.9 in the study and the control groups, respectively. Endoscopist satisfaction was good in 82%, moderate in 15%, and poor in 3% of ERCPs in the study group and good in 15%, moderate in 65%, and poor in 25% of ERCPs in the control group. The study group showed a shorter ERCP duration than the control group.

Conclusions:

Simethicone and otilonium bromide administered concomitantly reduce duodenal motility and foam/bubble formation, which facilitates papilla of Vater catheterization to reduce procedure time.
How much green does it take to be orange? Determining the cost associated with trauma center readiness
Authors: Ashley Dennis W. , Mullins Robert F. , Dente Christopher J. , Johns Tracy J. , Garlow Laura E. , Medeiros Regina S. , Atkins Elizabeth V. , Solomon Gina , Abston Dena , Ferdinand Colville H.
Published: February 2019

BACKGROUND

Readiness costs are real expenses incurred by trauma centers to maintain essential infrastructure to provide emergent services on a 24/7 basis. Although the components for readiness are well described in the American College of Surgeons' Resources for Optimal Care of the Injured Patient, the cost associated with each component is not well defined. We hypothesized that meeting the requirements of the 2014 Resources for Optimal Care of the Injured Patient would result in significant costs for trauma centers.

METHODS

The state trauma commission in conjunction with trauma medical directors, program managers, and financial officers of each trauma center standardized definitions for each component of trauma center readiness cost and developed a survey tool for reporting. Readiness costs were grouped into four categories: administrative/program support staff, clinical medical staff, in-house operating room, and education/outreach. To verify consistent cost reporting, a financial auditor analyzed all data. Trauma center outliers were further evaluated to validate variances. All level I/level II trauma centers (n = 16) completed the survey on 2016 data.

RESULTS

Average annual readiness cost is US $10,078,506 for a level I trauma center and US $4,925,103 for level IIs. Clinical medical staff was the costliest component representing 55% of costs for level Is and 64% for level IIs. Although education/outreach is mandated, levels I and II trauma centers only spend approximately US $100,000 annually on this category (1%–2%), demonstrating a lack of resources.

CONCLUSION

This study defines the cost associated with each component of readiness as defined in the Resources for Optimal Care of the Injured Patient manual. Average readiness cost for a level I trauma center is US $10,078,506 and US $4,925,103 for a level II. The significant cost of trauma center readiness highlights the need for additional trauma center funding to meet the requirements set forth by the American College of Surgeons.

LEVEL OF EVIDENCE

Economic and value-based evaluations, level III.
GFR Assessment of Living Kidney Donors Candidates
Authors: Gaillard François , Legendre Christophe , White Christine A.
Published: February 2019

Living kidney donation provides the best outcomes (survival, cost, and quality of life) of all renal replacement modalities. Living kidney donors, on the other hand, are at the increased risk of end-stage kidney disease (ESKD) after donation compared with healthy nondonors for multiple possible reasons. Extensive predonation screening is required to assess eligibility for donation to avoid the rejection of suitable candidates and minimize acceptance of donors with increased risk of ESKD. The association between the lower predonation glomerular filtration rate (GFR) and increased ESKD risk in donors highlights the relevance of GFR assessment for living kidney donor candidates. However, the method to evaluate GFR is still debated, and the thresholds of acceptable predonation GFR vary across guidelines. All guidelines favor GFR measurement with an exogenous tracer over estimated GFR, but only the British Transplant Society guidelines mandates it. While the Kidney Disease Improving Global Outcomes Group guidelines advocates for age-independent GFR thresholds, most other guidelines propose various age-dependent GFR thresholds with resulting profound differences in assessment of donor suitability between guidelines. Many important questions are not addressed by any guidelines, including the approach to discordant GFR measurement and estimated GFR results, the use of method-specific GFR thresholds and thresholds dependent on comorbidities or race. Further data are required exploring the associations between these variables and the course of postdonation GFR. Last, GFR evaluation studies conducted in approved donors and not in those initially presenting as potential candidates are questionable regarding their suitability for potential donor evaluation.
Impact of Aortoiliac Stenosis on Graft and Patient Survival in Kidney Transplant Recipients Using the TASC II Classification
Authors: Rijkse Elsaline , Kimenai Hendrikus J.A.N. , Roodnat Joke I. , Ten Raa Sander , Bijdevaate Diederik C. , van Dam Jacob L. , Muller Kelly , IJzermans Jan N.M. , van der Zijden Marcus A. , Minnee Robert C.
Published: February 2019

Background.

Patients with end-stage renal disease and aortoiliac stenosis are often considered ineligible for kidney transplantation, although kidney transplantation has been acknowledged as the best therapy for end-stage renal disease. The clinical outcomes of kidney transplantation in patients with aortoiliac stenosis are not well-studied. This study aimed to assess the impact of aortoiliac stenosis on graft and patient survival.

Methods.

This retrospective, single-center study included kidney transplant recipients transplanted between January 1, 2000, and December 31, 2016, who received contrast-enhanced imaging. Patients with aortoiliac stenosis were classified using the Trans-Atlantic Inter-Society Consensus (TASC) II classification and categorized as having TASC II A/B lesions or having TASC II C/D lesions. Patients without aortoiliac stenosis were functioning as controls.

Results.

A total number of 374 patients was included in this study (n = 88 with TASC II lesions, n = 286 as controls). Death-censored graft survival was similar to the controls. Patient and uncensored graft survival was decreased in patients with TASC II C/D lesions (log-rank test P < 0.001). Patients with TASC II C/D lesions had a higher risk of 90-day mortality (hazard ratio, 3.96; 95% confidence interval, 1.12–14.04). In multivariable analysis, having a TASC II C/D lesion was an independent risk factor for mortality (hazard ratio, 3.25; 95% confidence interval, 1.87–5.67; P < 0.001). Having any TASC II lesion was not a risk factor for graft loss (overall P = 0.282).

Conclusions.

Kidney transplantation in patients with TASC II A/B is feasible and safe without increased risk of perioperative mortality. TASC II C/D decreases patient survival. Death-censored graft survival is unaffected.
Use of Eculizumab for Active Antibody-mediated Rejection That Occurs Early Post–kidney Transplantation: A Consecutive Series of 15 Cases
Authors: Tan Ek Khoon , Bentall Andrew , Dean Patrick G. , Shaheen Mohammed F. , Stegall Mark D. , Schinstock Carrie A.
Published: February 2019

Background.

Active antibody-mediated rejection (AMR) that occurs during the amnestic response within the first month posttransplant is a rare but devastating cause of early allograft loss after kidney transplant. Prior reports of eculizumab treatment for AMR have been in heterogeneous patient groups needing salvage therapy or presenting at varied time points. We investigated the role of eculizumab as primary therapy for active AMR early posttransplant.

Methods.

We performed a retrospective observational study of a consecutive cohort of solitary kidney transplant recipients who were transplanted between January 1, 2014, and January 31, 2018, and had AMR within the first 30 days posttransplant and treated with eculizumab ± plasmapheresis.

Results.

Fifteen patients had early active AMR at a median (interquartile range [IQR]) of 10 (7–11) days posttransplant and were treated with eculizumab ± plasmapheresis. Thirteen cases were biopsy proven, and 2 cases were presumed on the basis of donor-specific antibody trends and allograft function. Within 1 week of treatment, the median estimated glomerular filtration rate increased from 21 to 34 mL/min (P = 0.001); and persistent active AMR was only found in 16.7% (2/12) of biopsied patients within 4–6 months. No graft losses occurred, and at last follow-up (median [IQR] of 13 [12–19] mo), the median IQR estimated glomerular filtration rate increased to 52 (46–60) mL/min.

Conclusions.

Prompt eculizumab treatment as primary therapy is safe and effective for early active AMR after kidney transplant or abrupt increases in donor-specific antibodies when biopsy cannot be performed for diagnosis confirmation.
Outcomes After Declining Increased Infectious Risk Kidney Offers for Pediatric Candidates in the United States
Authors: Bowring Mary G. , Jackson Kyle R. , Wasik Heather , Neu Alicia , Garonzik-Wang Jacqueline , Durand Christine , Desai Niraj , Massie Allan B. , Segev Dorry L.
Published: February 2019

Background.

Kidneys from infectious risk donors (IRD) confer substantial survival benefit in adults, yet the benefit of IRD kidneys to pediatric candidates remains unclear in the context of high waitlist prioritization.

Methods.

Using 2010–2016 Scientific Registry of Transplant Recipients data, we studied 2417 pediatric candidates (age <18 y) who were offered an IRD kidney that was eventually used for transplantation. We followed candidates from the date of first IRD kidney offer until the date of death or censorship and used Cox regression to estimate mortality risk associated with IRD kidney acceptance versus decline, adjusting for age, sex, race, diagnosis, and dialysis time.

Results.

Over the study period, 2250 (93.1%) pediatric candidates declined and 286 (11.8%) accepted an IRD kidney offer; 119 (41.6%) of the 286 had previously declined a different IRD kidney. Cumulative survival among those who accepted versus declined the IRD kidney was 99.6% versus 99.4% and 96.3% versus 97.8% 1 and 6 years post decision, respectively (P = 0.1). Unlike the substantial survival benefit seen in adults (hazard ratio = 0.52), among pediatric candidates, we did not detect a survival benefit associated with accepting an IRD kidney (adjusted hazard ratio: 0.791.723.73, P = 0.2). However, those who declined IRD kidneys waited a median 9.6 months for a non-IRD kidney transplant (11.2 mo among those <6 y, 8.8 mo among those on dialysis). Kidney donor profile index (KDPI) of the eventually accepted non-IRD kidneys (median = 13, interquartile range = 6–23) was similar to KDPI of the declined IRD kidneys (median = 16, interquartile range = 9–28).

Conclusions.

Unlike in adults, IRD kidneys conferred no survival benefit to pediatric candidates, although they did reduce waiting times. The decision to accept IRD kidneys should balance the advantage of faster transplantation against the risk of infectious transmission.
Defining early events of Epstein–Barr virus (EBV) infection in immortalized nasopharyngeal epithelial cells using cell-free EBV infection
Authors: Pang Pei Shin , Liu Tengfei , Lin Weitao , Tsang Chi-Man , Yip Yim-Ling , Zhou Yuan , Guan Xin-Yuan , Chan Ronald Cheong-Kin , Tsao Sai-Wah , Deng Wen
Published: February 2019

Epstein–Barr virus (EBV) infection is strongly associated with nasopharyngeal carcinoma, a common cancer in Southeast Asia and certain regions of Africa. However, the dynamics of EBV episome maintenance in infected nasopharyngeal epithelial (NPE) cells remain largely undefined. Here, we report the establishment of a highly efficient cell-free EBV infection method for NPE cells. By using this method, we have defined some of the dynamic events involved in the early stage of EBV infection in NPE cells. We report, for the first time, a rapid loss of EBV copies from infected NPE cells during the first 12–72 h post-infection. The rate of EBV loss slowed at later stages of infection. Live cell imaging revealed that the freshly infected NPE cells were delayed in entry into mitosis compared with uninfected cells. Freshly infected NPE cells transcribed significantly higher levels of lytic EBV genes BZLF1 and BMRF1 yet significantly lower levels of EBER1/2 than stably infected NPE cells. Notably, there were very low or undetectable levels of protein expressions of EBNA1, LMP1, Zta and Rta in freshly infected NPE cells, whereas EBNA1 and LMP1 proteins were readily detected in stable EBV-infected NPE cells. The kinetics of EBV loss and the differential EBV gene expression profiles between freshly and stably infected NPE cells are in line with the suggestion of epigenetic changes in the EBV genome that affect viral gene expression and the adaptation of host cells to EBV infection to maintain persistent EBV infection in NPE cells.
Bessel beam tomography for fast volume imaging
Authors: Valle Andres Flores , Seelig Johannes D.
Published: February 2019

Light microscopy on dynamic samples, for example neural activity in the brain, requires imaging large volumes at high rates. Here, we develop a tomography approach for scanning fluorescence microscopy which allows recording volume images at frame scan rates. Volumes are imaged by simultaneously recording four independent projections at different angles using temporally multiplexed, tilted Bessel beams. From the resulting projections, volumes are reconstructed using inverse Radon transforms combined with three dimensional convolutional neural networks (U-net). This tomography approach is suitable for experiments requiring fast volume imaging of sparse samples, as for example often encountered when imaging neural activity in the brain.
Human loss-of-function variants suggest that partial LRRK2 inhibition is a safe therapeutic strategy for Parkinson’s disease
Authors: Whiffin Nicola , Armean Irina M. , Kleinman Aaron , Marshall Jamie L. , Minikel Eric V. , Karczewski Konrad J. , Cummings Beryl B. , Francioli Laurent , Laricchia Kristen , Wang Qingbo , Guan Anna , Alipanahi Babak , Morrison Peter , Baptista Marco A.S. , Merchant Kalpana M. ,   Genome Aggregation Database Production Team,   Genome Aggregation Database Consortium, Ware James S. , Havulinna Aki S. , Iliadou Bozenna , Lee Jung-Jin , Nadkarni Girish N. , Whiteman Cole ,   the 23andMe Research Team, Daly Mark , Esko Tõnu , Hultman Christina , Loos Ruth J.F. , Milani Lili , Palotie Aarno , Pato Carlos , Pato Michele , Saleheen Danish , Sullivan Patrick F. , Alföldi Jessica , Cannon Paul , MacArthur Daniel G.
Published: February 2019

Human genetic variants causing loss-of-function (LoF) of protein-coding genes provide natural in vivo models of gene inactivation, which are powerful indicators of gene function and the potential toxicity of therapeutic inhibitors targeting these genes1,2. Gain-of-kinase-function variants in LRRK2 are known to significantly increase the risk of Parkinson’s disease3,4, suggesting that inhibition of LRRK2 kinase activity is a promising therapeutic strategy. Whilst preclinical studies in model organisms have raised some on-target toxicity concerns5–8, the biological consequences of LRRK2 inhibition have not been well characterized in humans. Here we systematically analyse LoF variants in LRRK2 observed across 141,456 individuals sequenced in the Genome Aggregation Database (gnomAD)9 and over 4 million participants in the 23andMe genotyped dataset, to assess their impact at a molecular and phenotypic level. After thorough variant curation, we identify 1,358 individuals with high-confidence predicted LoF variants in LRRK2, several with experimental validation. We show that heterozygous LoF of LRRK2 reduces LRRK2 protein level by ~50% but is not associated with reduced life expectancy, or with any specific phenotype or disease state. These data suggest that therapeutics that downregulate LRRK2 levels or kinase activity by up to 50% are unlikely to have major on-target safety liabilities. Our results demonstrate the value of large scale genomic databases and phenotyping of human LoF carriers for target validation in drug discovery.
Ontology-based prediction of cancer driver genes
Authors: Althubaiti Sara , Karwath Andreas , Dallol Ashraf , Noor Adeeb , Alkhayyat Shadi Salem , Alwassia Rolina , Mineta Katsuhiko , Gojobori Takashi , Beggs Andrew D , Schofield Paul N , Gkoutos Georgios V , Hoehndorf Robert
Published: February 2019

Identifying and distinguishing cancer driver genes among thousands of candidate mutations remains a major challenge. Accurate identification of driver genes and driver mutations is critical for advancing cancer research and personalizing treatment based on accurate stratification of patients. Due to inter-tumor genetic heterogeneity, many driver mutations within a gene occur at low frequencies, which make it challenging to distinguish them from non-driver mutations. We have developed a novel method for identifying cancer driver genes. Our approach utilizes multiple complementary types of information, specifically cellular phenotypes, cellular locations, functions, and whole body physiological phenotypes as features. We demonstrate that our method can accurately identify known cancer driver genes and distinguish between their role in different types of cancer. In addition to confirming known driver genes, we identify several novel candidate driver genes. We demonstrate the utility of our method by validating its predictions in nasopharyngeal cancer and colorectal cancer using whole exome and whole genome sequencing.