bluuebunny/crossref_metadata_2025 huggingface dataset:
Conjunctival Impression Cytology and Tear-Film Changes in Patients With Inflammatory Bowel Disease
Authors: Doğan Mustafa , Özcan Serkan , Acartürk Gürsel , Özdemir Çiğdem
Published: July 2018

Purpose:

To evaluate the ocular surface changes and tear-film functions in patients with inflammatory bowel disease (IBD).

Methods:

The IBD group included 57 patients, and the control group included 29 healthy individuals. The Schirmer I test, tear breakup time (TBUT), corneal and conjunctiva fluorescent staining, and conjunctival impression cytology tests were performed to both groups.

Results:

The rate of dry eye was 56.1% and 10.3% in the IBD and control groups, respectively, as assessed by the Schirmer I test (P<0.001). The rate of dry eye was 52.6% and 20.8% in the IBD and control groups, respectively through TBUT (P=0.004). The Ocular Surface Disease Index scores of the IBD group (15.25±7.31) were significantly higher than the control group (11.75±7.33) (P=0.039). According to the Oxford scheme, mild-to-moderate staining was 54.4% in the IBD group and 6.9% in the control group (P<0.001). Nelson Staging System showed that 69% of the IBD group had stage 2 or 3 impression cytology, whereas none of the control group had stage 2 or 3 impression cytology (P<0.001). Using the Schirmer I test, the rate of dry eye was 55.8% of the patients with IBD receiving 5-aminosalicylic acid (5-ASA) and 61.5% of the patients with IBD receiving both 5-ASA and azathioprine (P=0.485).

Conclusions:

Our study results showed that dry eye was 3 times higher in the IBD group than the control group. But, the duration of disease seems not to have effect on dry eye.
“Eye Dropping”—A Case Report of Transconjunctival Lysergic Acid Diethylamide Drug Abuse
Authors: Lo Danielle , Cobbs Lucy , Chua Michael , Young Joshua , Haberman Ilyse D. , Modi Yasha
Published: July 2018

Purpose:

To report a case of bilateral toxic corneal and conjunctival epitheliopathy secondary to administration of filter paper impregnated with lysergic acid diethylamide (LSD) in the inferior conjunctival fornices.

Methods:

This is a single case report of an 18-year-old man who presented to the emergency department with acute, bilateral eye pain and redness of 24 hours. The patient admitted to placing folded strips of blotting paper impregnated with LSD into the inferior fornices of his eyes the previous night.

Results:

The patient was found to have localized bilateral corneal and conjunctival abrasions with underlying subconjunctival hemorrhage. Conjunctival abrasion was “kissing,” involving the bulbar and palpebral conjunctiva, corresponding to the presumed location of the filter paper. There was no corneal stromal opacification. He was lost to follow up within 1 week of initial presentation but stated that his symptoms improved.

Conclusions:

To the best of our knowledge, this is the first reported case of bilateral hemorrhagic conjunctival abrasion and corneal abrasion secondary to LSD. “Kissing” conjunctival lesions, which have been previously reported with heroin use, should raise suspicion for drug abuse.
Community Health Workers as an Extension of Care Coordination in Primary Care
Authors: Gunderson Jean M. , Wieland Mark L. , Quirindongo-Cedeno Onelis , Asiedu Gladys B. , Ridgeway Jennifer L. , O'Brien Michael W. , Nelson Tara M. , Buzard Ron , Campbell Chad , Njeru Jane W.
Published: July 2018

Community health workers (CHWs) bring their unique capacity as liaisons for patients, communities, and health care systems to health care teams. We describe the collaborative development of a community-based CHW program to address the social determinants of health that affect patients. This cosupervisory, generalist CHW model provides an innovative template for cocreation of patient-centered infrastructure and resourcing within an evolving and replicable holistic care continuum across patient ages, diagnoses, health care payers, and communities to promote health equity. The program has been effective in decreasing health care utilization and cost.
Benchtop von Willebrand Factor Testing: Comparison of Commercially Available Ventricular Assist Devices and Evaluation of Variables for a Standardized Test Method
Authors: Coghill Phillip A. , Kanchi Suren , Azartash-Namin Zheila J. , Long James W. , Snyder Trevor A.
Published: July 2018

Gastrointestinal bleeding occurs in 20–30% of patients receiving ventricular assist devices (VADs) due, in part, to acquired von Willebrand syndrome. We examined factors to optimize a benchtop method to quantify changes in von Willebrand Factor (VWF) multimer distribution and function in VADs, then applied them to evaluate commercially available devices. Human plasma was circulated through flow loops with VADs. Several experimental conditions were examined, including temperature, viscosity, and enzyme inhibition. Samples were analyzed for VWF collagen-binding activity (VWF:CB) and VWF antigen level. von Willebrand Factor multimer profiles were quantified using gel electrophoresis, near-infrared in-gel visualization, and densitometric analysis. The VWF:CB/antigen ratio in the HeartMate II, CentriMag, and HVAD exhibited average decreases of 46%, 44%, and 36% from baseline after 360 minutes of operation. High molecular weight (hVWF) multimer loss occurred within 30 minutes, although the Levacor and control loop profiles were unchanged. Varying temperature and viscosity altered hVWF degradation rate, but not the final results. Inhibition of a disintegrin and metalloprotease with thrombospondin type 1 repeats, member 13 (ADAMTS13) can potentially distinguish mechanoenzymatic cleavage of VWF from mechanical degradation. We developed a repeatable benchtop method to evaluate VWF compatibility of VADs similar to hemolysis testing that can be adopted for preclinical VAD evaluation.
Optimal Methods to Secure Extracorporeal Membrane Oxygenation Bicaval Dual-Lumen Cannulae: What Works?
Authors: Tignanelli Christopher J. , Weinberg Allison , Napolitano Lena M.
Published: July 2018

Ambulation while on extracorporeal membrane oxygenation (ECMO) is critical to facilitate native pulmonary recovery for patients with acute respiratory failure and is a prerequisite for listing for lung transplantation to achieve optimal outcomes. The development of a bicaval dual-lumen cannula capable of providing venovenous (VV) ECMO support via the internal jugular vein has greatly facilitated ambulation and rehabilitation programs. But cannula dislodgement is a serious concern with ambulation and rehabilitation, especially when minor cannula migration can significantly impact VV-ECMO flow. We review an optimal technique to secure dual-lumen cannula to facilitate early mobility, ambulation, and rehabilitation and prevent ECMO cannula dislodgement.
Ethnoracial Disparities in Medicare Annual Wellness Visit Utilization
Authors: Lind Kimberly E. , Hildreth Kerry , Lindrooth Richard , Crane Lori A. , Morrato Elaine , Perraillon Marcelo Coca
Published: July 2018

Introduction:

In 2011, Medicare began offering annual preventive care visits (annual wellness visit; AWV) to beneficiaries at no charge. Providing free preventive care supports primary and secondary prevention of chronic disease and may reduce ethnoracial disparities in health outcomes.

Objectives:

To estimate AWV utilization trends by ethnoracial group in a nationally representative sample of the Medicare population.

Research Design:

We estimated the probability of AWV utilization using probit regression models with beneficiary-reported ethnoracial group as the primary predictor and demographics, socioeconomic indicators, and factors related to access and utilization of health care as covariates.

Subjects:

In total, 14,687 fee-for-service Medicare beneficiaries aged 66 years or older who participated in the Medicare Current Beneficiary Survey 2011–2013.

Measures:

AWV utilization was identified using procedure codes.

Results:

Overall AWV utilization increased from 8.1% (2011) to 13.4% (2013). In 2011, utilization was highest in non-Hispanic white (8.5%) and lowest in non-Hispanic black (4.5%) beneficiaries. Utilization increased the most in non-Hispanic black beneficiaries, to 15.4% in 2013. Significant differences in AWV utilization by non-Hispanic black and Hispanic/Latino beneficiaries were found in unadjusted models, but did not persist after controlling for income and education. Having a usual (nonemergent) place of care and a nonrural residence were strong predictors of utilization.

Conclusions:

Utilization of the AWV has increased modestly since its introduction, but remains low. Utilization varies by ethnoracial group, with disparities largely explained by differences in income and education. Further efforts are needed to evaluate AWV utilization and effectiveness, especially among low socioeconomic status ethnoracial minorities.
Using the Relational Coordination Instrument With a Diverse Patient Sample
Authors: Wells Rebecca , Armstrong Trey W. , Brossart Daniel F.
Published: July 2018

Background:

The Relational Coordination (RC) instrument has been used extensively in the context of health care interprofessional coordination. However, the instrument’s applicability to patient experiences of their interactions with professionals is largely untested.

Objectives:

This study’s objectives were to determine: (1) whether the RC instrument could be modified for phone administration to yield internally consistent results when used with a diverse group of patients with complex health needs; and (2) whether the RC factor was invariant across patients of differing education, levels of emotional problems, race, and ethnicity, thereby showing similar interpretation of items across these groups.

Research Design:

The RC instrument was administered through a phone survey to patients in Texas (n=346) who reported receiving care coordination. Data collection occurred between 2014 and 2016. Cronbach α coefficients and confirmatory factor analysis were used to determine whether the original set of RC items could be used for phone surveys with patients. Factorial invariance testing was used to assess how consistently the instrument was interpreted across patient subgroups.

Results:

The RC scale generally met acceptable α statistic and confirmatory factor analysis thresholds for internal consistency. Factorial invariance results indicated that the scale also generally performed consistently across patient subgroups.

Conclusions:

This study provides preliminary evidence that the RC instrument can be used for surveying diverse patient populations. Future use of this instrument with patients can better reflect their experiences as partners with professionals in improving their health.
Does the Patient-centered Medical Home Model Change Staffing and Utilization in the Community Health Centers?
Authors: Park Jeongyoung , Wu Xiaoli , Frogner Bianca K. , Pittman Patricia
Published: July 2018

Background:

Few studies have looked under the hood of practice redesign to understand whether and, if so, how staffing changed with the adoption of patient-centered medical home (PCMH), and whether these staffing changes impacted utilization.

Objectives:

To examine the workforce transformation occurring in community health centers that have achieved PCMH status, and to assess the relationship of those changes to utilization, as measured by the number of visits.

Research Design, Subjects, Measures:

Using a difference-in-differences approach, we compared staffing and utilization outcomes in 450 community health centers that had adopted a PCMH model between 2007 and 2013 to a matched sample of 243 nonadopters located in the 50 states and the District of Columbia.

Results:

We found that adopting a PCMH model was significantly associated with a growth in use of advanced practice staff (nurse practitioners and physician assistants) [0.53 full-time equivalent (FTE), 8.77%; P<0.001], other medical staff (medical assistants, nurse aides, and quality assurance staff) (1.23 FTE, 7.46%; P=0.001), mental health/substance abuse staff (0.73 FTE, 17.63%; P=0.005), and enabling service staff (case managers and health educators) (0.36 FTE, 6.14%; P=0.079), but not primary care physicians or nurses. We did not observe a significant increase in utilization, as measured in total number of visits per year. However, the visits marginally attributed to advanced practice staff (539 FTE, 0.89%; P=0.037) and mental health/substance abuse staff (353 FTE, 0.59%; P=0.051) significantly increased.

Conclusions:

Our findings suggest that the implementation of PCMH actively reengineers staff composition and this, in turn, results in changes in marginal utilization by each staff type.
Emerging applications of aptamers for anticoagulation and hemostasis
Authors: Chabata Charlene V. , Frederiksen James W. , Sullenger Bruce A. , Gunaratne Ruwan
Published: July 2018

Purpose of review

Since the selection of the first thrombin-binding aptamer in 1992, the use of nucleic acid aptamers to target specific coagulation factors has emerged as a valuable approach for generating novel anticoagulant and procoagulant therapeutics. Herein, we highlight the most recent discoveries involving application of aptamers for those purposes.

Recent findings

Learning from the successes and pitfalls of the FIXa-targeting aptamer pegnivacogin in preclinical and clinical studies, the latest efforts to develop antidote-controllable anticoagulation strategies for cardiopulmonary bypass that avoid unfractionated heparin involve potentiation of the exosite-binding factor X (FX)a aptamer 11F7t by combination with either a small molecule FXa catalytic site inhibitor or a thrombin aptamer. Recent work has also focused on identifying aptamer inhibitors of contact pathway factors such as FXIa and kallikrein, which may prove to be well tolerated and effective antithrombotic agents in certain clinical settings. Finally, new approaches to develop procoagulant aptamers to control bleeding associated with hemophilia and other coagulopathies involve targeting activated protein C and tissue plasminogen activator.

Overall, these recent findings exemplify the versatility of aptamers to modulate a variety of procoagulant and anticoagulant factors, along with their capacity to be used complementarily with other aptamers or drugs for wide-ranging applications.
FDG PET/CT of Metabolic Myopathy With Posttreatment Follow-up
Authors: McNamee Anitia , Robertson Thomas , Sounness Brett , O’Gorman Patricia
Published: July 2018

A 38-year-old woman presented with extreme fatigue and multiple lung nodules. She was referred for a PET/CT, which demonstrated multiple FDG-avid pulmonary nodules and lymph nodes with intense uptake within multiple muscle groups predominantly involving the paraspinal muscles and muscles of mastication. Histopathology of a paraspinal muscle biopsy revealed increased skeletal muscle lipid stores and increased mitochondria with normal morphology. This abnormality is seen in metabolic myopathy due to a disorder of fatty acid oxidation. Transbronchial biopsy showed no evidence of sarcoidosis. The patient was commenced on carnitine and riboflavin supplementation, and a follow-up PET/CT was performed.
The Role of SPECT/CT of Foot and Ankle in the Evaluation of Heel Pain
Authors: Lee Minkyung , Kim Bom Soo , Kim Yeoju , Hyun In Young
Published: July 2018

Heel pain is a common symptom in foot and ankle disorders. Typical heel pain can be assessed according to the patient’s history and the location of pain. In some atypical inconclusive cases, bone SPECT/CT is the upcoming imaging modality for the detection of causes of heel pain. We present the case of 57-year-old man with atypical heel pain, plantar and Achilles spurs. SPECT/CT images demonstrated increased bony activity in arthritis of midfoot, not plantar and Achilles spurs. It suggests potential role of SPECT/CT in the evaluation and management of heel pain by showing hidden pathology of foot and ankle.
Intense FDG Uptake in the Muscles Due to Severe Vomiting
Authors: Liu Jie , Wang Wei , Yuan Leilei , Kan Ying , Yang Jigang
Published: July 2018

A 22-year-old woman with acute lymphoblastic leukemia underwent FDG PET/CT to evaluate possible extramedullary disease. The patient experienced severe nausea and vomiting due to ongoing chemotherapy. The image demonstrated increased FDG uptake in multiple muscle groups, including intercostal, bilateral external oblique, internal oblique, transverse abdominal muscles, and psoas major. One week after the patient stopped vomiting, a repeated PET/CT showed much less muscle uptake.
18F-FDOPA PET/CT of Nonfunctioning Paraganglioma of the Gastroepiploic Pedicle
Authors: Leroy Freschini Benjamin , Addeo Pietro , Averous Gerlinde , Goichot Bernard , Bachellier Philippe , Imperiale Alessio
Published: July 2018

We report the case of a 54-year-old woman with a nonfunctioning paraganglioma arising from the gastroepiploic pedicle demonstrated by 18F-FDOPA PET/CT. Because gastroepiploic arcade can be assimilated to the gastric mesentery, this tumor has been classified as a mesenteric paraganglioma (PGL). Neural crest cells are a multipotent population of cells characterized by effective migratory properties potentially explaining PGL atypical localization as in the mesentery. Mesenteric PGLs are often nonfunctioning and can mimic gastric, colic, or pancreatic primary tumor because of their anatomical boundaries, making more difficult the diagnosis on preoperative imaging.
Examining Factors Related to Health-Related Quality of Life in People With Parkinson’s Disease
Authors: Kwok JoJo Yan Yan , Auyeung Man , Chan Helen Yue Lai
Published: July 2018

Purpose

Parkinson’s disease (PD) results in a range of dysfunctions and disabilities as it progresses to later stages. All these not only affect a patient’s physical well-being but also emotional, social, and spiritual well-being. To tailor interventions that can address these concerns, this study aimed to examine the impacts of PD on their health-related quality of life (HRQOL).

Design

A cross-sectional study with 123 PD patients.

Methods

Measures included the following: Hospital Anxiety and Depression Scale, Unified PD Rating Scale–Motor Examination, Hoehn and Yahr Stage, PD Questionnaire-8. Associating factors of HRQOL was examined using stepwise linear regression.

Findings

Psychological distress and functional impairment are significantly associated with the HRQOL of the PD population. Psychological distress is associated most to the variance of HRQOL (42.4%).

Conclusion

Considering that PD is chronic, rehabilitation programs should be applied to address not just functional but also psychosocial needs of PD patients.

Clinical Relevance

Early recognition and management of psychological distress in PD patients is indispensable to promote their HRQOL.
The RESTORE Randomized Controlled Trial
Authors: O’Neill Linda M. , Guinan Emer , Doyle Suzanne L. , Bennett Annemarie E. , Murphy Conor , Elliott Jessie A. , O'Sullivan Jacintha , Reynolds John V. , Hussey Juliette
Published: July 2018

Objective:

The Rehabilitation Strategies in Esophagogastric cancer (RESTORE) randomized controlled trial evaluated the efficacy of a 12-week multidisciplinary program to increase the cardiorespiratory fitness and health-related quality of life (HRQOL) of esophagogastric cancer survivors.

Background:

Patients following treatment for esophagogastric cancer are at risk of physical deconditioning, nutritional compromise, and sarcopenia. Accordingly, compelling rationale exists to target these impairments in recovery.

Methods:

Disease-free patients treated for esophagogastric cancer were randomized to either usual care or the 12-week RESTORE program (exercise training, dietary counseling, and multidisciplinary education). The primary outcome was cardiopulmonary exercise testing (VO2peak). Secondary outcomes included body composition (bioimpedance analysis), and HRQOL (EORTC-QLQ-C30). Outcomes were assessed at baseline (T0), postintervention (T1), and at 3-month follow-up (T2).

Results:

Twenty-two participants were randomized to the control group [mean (standard deviation) age 64.14 (10.46) yr, body mass index 25.67 (4.83) kg/m2, time postsurgery 33.68 (19.56) mo], and 21 to the intervention group [age 67.19(7.49) yr, body mass index 25.69(4.02) kg/m2, time postsurgery 23.52(15.23) mo]. Mean adherence to prescribed exercise sessions were 94(12)% (supervised) and 78(27)% (unsupervised). Correcting for baseline VO2peak, the intervention arm had significantly higher VO2peak at both T1, 22.20 (4.35) versus 21.41 (4.49) mL · min−1 · kg−1, P < 0.001, and T2, 21.75 (4.27) versus 20.74 (4.65) mL · min−1 · kg−1, P = 0.001, compared with the control group. Correcting for baseline values, no changes in body composition or HRQOL were observed.

Conclusions:

The RESTORE program significantly improved cardiorespiratory fitness of disease-free patients after esophagogastric cancer surgery, without compromise to body composition. This randomized controlled trial provides proof of principle for rehabilitation programs in esophagogastric cancer.

Clinical Trial Registration Number:

NCT03314311.
No Clinical Benefit of Intramuscular Delivery of Bone Marrow-derived Mononuclear Cells in Nonreconstructable Peripheral Arterial Disease
Authors: Lindeman Jan H. N. , Zwaginga Jaap Jan , Kallenberg-Lantrua Graziella , van Wissen Rob C. , Schepers Abbey , van Bockel Hajo J. , Fibbe Willem E. , Hamming Jaap F.
Published: July 2018

Background and Aims:

Prospects for no-option, end-stage peripheral artery disease (PAD) patients remain poor. Although results from open and semiblinded studies fuel hope for cell-based strategies in no-option patients, so far conclusions from the available placebo-controlled studies are not supportive. With the intention to end the remaining controversy with regard to cell therapy for PAD we conducted a confirmatory, double-blinded randomized placebo-controlled phase 3 trial.

Study Design:

This randomized controlled trial was registered (NCT00539266). Inclusion criteria included stable or progressive disabling PAD, no imminent need for amputation, absent accepted options for revascularization. Diabetic disease was an exclusion criterion. Bone marrow (500–700 mL) was harvested and bone marrow-derived mononuclear cells were concentrated to 40 mL. Concentrated cells or placebo (diluted blood) were intramuscularly injected at 40 locations of the calf muscle.

Results:

Fifty-four patients (mean (sd) age 58.2 (14.2) yrs, 58% males) were randomized. Twenty-eight patients received BM-MNCs, 26 placebo. Baseline criteria were similar in the 2 groups. No significant differences were observed for the primary (number of amputations, (pain free) walking distance) and secondary outcome parameters (ankle brachial index, pain scores, quality of life (SF-36)).

Discussion:

This fully blinded replication trial of autologous BM-MNC fails to confirm a benefit for cell therapy in no-option PAD patients, consequently BM-MNC therapy should not be offered as a clinical treatment. Apparent contrasting conclusions from open and controlled studies underscore the importance of a controlled trial design in evaluating cell-based interventions in PAD.
An Academic Relative Value Unit System for Incentivizing the Academic Productivity of Surgery Faculty Members
Authors: LeMaire Scott A. , Trautner Barbara W. , Ramamurthy Uma , Green Susan Y. , Zhang Qianzi , Fisher William E. , Rosengart Todd K.
Published: July 2018

Objective:

The objective of this study was to evaluate a new academic relative-value unit (aRVU) scoring system linked to faculty compensation and analyze its association with overall departmental academic productivity.

Summary Background Data:

Faculty are often not incentivized or financially compensated for educational and research activities crucial to the academic mission.

Methods:

We launched an online, self-reporting aRVU system in 2015 to document and incentivize the academic productivity of our faculty. The system captured 65 specific weighted scores in 5 major categories of research, education, innovation, academic service, and peer review activities. The aRVU scores were rank-aggregated annually, and bonuses were distributed to faculty members in 3 tiers: top 10%, top third, and top half. We compared pre-aRVU (academic year 2015) to post-aRVU (academic year 2017) departmental achievement metrics.

Results:

Since 2015, annual aRVU bonuses totaling $493,900 were awarded to 59 faculty members (58% of eligible department faculty). Implementing aRVUs was associated with significant increases in several key departmental academic achievement metrics: presentations (579 to 862; P = 0.02; 49% increase), publications (390 to 446; P = 0.02; 14%), total research funding ($4.6 M to $8.4 M; P < 0.001; 83%), NIH funding ($0.6 M to $3.4 M; P < 0.001; 467%), industry-sponsored clinical trials (8 to 23; P = 0.002; 188%), academic society committee positions (226 to 298; P < 0.001; 32%), and editorial leadership positions (50 to 74; P = 0.01; 48%).

Conclusions:

Implementing an aRVU system was associated with increases in departmental academic productivity. Although other factors undoubtedly contributed to these increases, an aRVU program may represent an important mechanism for tracking and rewarding academic productivity in surgery departments.
Hyperthyroidism is Underdiagnosed and Undertreated in 3336 Patients
Authors: Asban Ammar , Chung Sebastian K. , Tresler Margaret A. , Huilgol Priyanka , Xie Rongbing , Kirklin James K. , Balentine Courtney J. , Lindeman Brenessa M. , Chen Herbert
Published: July 2018

Objective:

The aim of this study was to determine the prevalence of undiagnosed and untreated hyperthyroidism among patients with suppressed thyroid-stimulating hormone (TSH).

Background:

Hyperthyroidism can significantly diminish patient quality of life and increase the financial burden on patients and health systems. We hypothesized that many patients with hyperthyroidism remain undiagnosed because physicians fail to recognize and evaluate suppressed TSH as the first indication of disease.

Methods:

We reviewed administrative data on 174011 patients with TSH measured at a tertiary referral center between 2011 and 2017 to identify individuals with hyperthyroidism (TSH <0.05 mU/L) and their subsequent outcomes: evaluation (measurement of T4, T3, radioactive iodine (RAI) uptake scan, thyroid-stimulating immunoglobulin, thyroid peroxidase antibodies) diagnosis, referral and treatment. We used Kaplan-Meier methods and multivariable time-related parametric hazard modeling to measure our outcomes.

Results:

We found 3336 patients with hyperthyroidism. The mean age of our cohort was 52 ± 17 years, with 79% females and 59% whites. Only 1088 patients (33%) received any appropriate evaluation and hyperthyroidism remained undiagnosed in 37% of patients who had the appropriate workup. Among those diagnosed with hyperthyroidism, only 21% were referred for surgery and 34% received RAI. Predictors for hyperthyroidism diagnosis include lower TSH (0.01u/L), younger age, African-American race, private commercial insurance, being seen in an outpatient setting, absence of medical comorbidities, presentation with ophthalmopathy, or weight loss.

Conclusions:

Hyperthyroidism is frequently unrecognized and untreated, which can lead to adverse outcomes and increased costs. Improved systems for detection and treatment of hyperthyroidism are needed to address this gap in care.
IdeS (Imlifidase): A Novel Agent That Cleaves Human IgG and Permits Successful Kidney Transplantation Across High-strength Donor-specific Antibody
Authors: Lonze Bonnie E. , Tatapudi Vasishta S. , Weldon Elaina P. , Min Elijah S. , Ali Nicole M. , Deterville Cecilia L. , Gelb Bruce E. , Benstein Judith A. , Dagher Nabil N. , Wu Ming , Montgomery Robert A.
Published: July 2018

Objectives:

The presence of a donor-specific positive crossmatch has been considered to be a contraindication to kidney transplantation because of the risk of hyperacute rejection. Desensitization is the process of removing hazardous preformed donor-specific antibody (DSA) in order to safely proceed with transplant. Traditionally, this involves plasmapheresis and intravenous immune globulin treatments that occur over days to weeks, and has been feasible when there is a living donor and the date of the transplant is known, allowing time for pre-emptive treatments. For sensitized patients without a living donor, transplantation has been historically difficult.

Summary of Background Data:

IdeS (imlifidase) is an endopeptidase derived from Streptococcus pyogenes which has specificity for human IgG, and when infused intravenously results in rapid cleavage of IgG.

Methods:

Here we present our single-center's experience with 7 highly sensitized (cPRA98–100%) kidney transplant candidates who had DSA resulting in positive crossmatches with their donors (5 deceased, 2 living) who received IdeS within 24 hours prior to transplant.

Results:

All pre-IdeS crossmatches were positive and would have been prohibitive for transplantation. All crossmatches became negative post-IdeS and the patients underwent successful transplantation. Three patients had DSA rebound and antibody-mediated rejection, which responded to standard of care therapies. Three patients had delayed graft function, which ultimately resolved. No serious adverse events were associated with IdeS. All patients have functioning renal allografts at a median follow-up of 235 days.

Conclusion:

IdeS may represent a groundbreaking new method of desensitization for patients who otherwise might have no hope for receiving a lifesaving transplant.
Per-oral Pyloromyotomy (POP) for Medically Refractory Gastroparesis
Authors: Rodriguez John , Strong Andrew T. , Haskins Ivy N. , Landreneau Joshua P. , Allemang Matthew T. , El-Hayek Kevin , Villamere James , Tu Chao , Cline Michael S. , Kroh Matthew , Ponsky Jeffrey L.
Published: July 2018

Objective:

For patients with gastroparesis, temporary pyloric disruption has been shown to improve symptoms and gastric emptying. Per-oral pyloromyotomy (POP) is an innovative endoscopic procedure to divide the pylorus from within a submucosal tunnel, as a corollary to surgical pyloromyotomy. Here we evaluate subjective and objective outcomes 12-weeks after POP at a high volume center.

Methods:

The first 100 consecutive patients undergoing POP were included, with procedure dates between January 2016 and October 2017. Patients were evaluated using the Gastroparesis Cardinal Symptom Index (GCSI), and 4-hour solid-phase scintigraphic gastric emptying studies (GES) prior to procedure and at 90 days post-POP

Results:

The study cohort was 85% female with a mean age of 45.0 ± 14.6 years. Gastroparesis etiologies were divided among idiopathic (56%), diabetic (21%), postsurgical (19%), and other in 4%. There were 67% of the patients who had previous endoscopic or surgical interventions for gastroparesis. Most POP procedures were performed in the operating room (97%) and were completed in an average of 33 minutes. Ten patients incurred complications (10%), which included 1 diagnostic laparoscopy and 2 cases of gastrointestinal bleeding. Overall GCSI improved from a preoperative mean of 3.82 ± 0.86 to 2.54 ± 1.2 (P < 0.001). The improvement in each GCSI subscore was also highly statistically significant. Among the patients with postoperative GES available, 78% had objectively better 4-hour emptying with a mean improvement in retention by 23.6% (P < 0.001). This included 57% of patients with normal gastric emptying post-POP.

Conclusion:

For patients with medically refractory gastroparesis, POP results in both subjective and objective improvement in the majority of patients. Prior intervention does not obviate POP as a therapeutic option. POP should be included along the treatment algorithm for patients with gastroparesis as an organ-sparing procedure.
Timing of Carotid Endarterectomy After Stroke
Authors: Tanious Adam , Pothof Alexander B. , Boitano Laura T. , Pendleton Alaska A. , Wang Linda J. , de Borst Gert J. , Rattner David W. , Schermerhorn Marc L. , Eslami Mohammad H. , Malas Mahmoud B. , Eagleton Matthew J. , Clouse William Darrin , Conrad Mark F.
Published: July 2018

Objective:

Our objective was to identify the postoperative risk associated with different timing intervals of repair.

Background:

Timing of carotid intervention in poststroke patients is widely debated with the scales balanced between increased periprocedural risk and recurrent neurologic event. National database reviews show increased risk to patients treated within the first 2 days of a neurologic event compared to those treated after 6 days.

Methods:

Utilizing Vascular Quality Initiative data, all carotid interventions performed on stroke patients between the years 2012 and 2017 were queried. Patients were then stratified based on the timing of surgery from their stroke (<48 hours, 3–7 days, 8–14 days, >15 days). Major outcomes included postoperative stroke, death, and myocardial infarction.

Results:

A total of 8404 patients were included being predominantly men (5281, 62.8%), with an average age of 69 (±10). Patients treated at greater than 8 days showed significantly less risk of postoperative combined stroke/death and postoperative stroke. There were no significant differences in postoperative stroke or death between the 8 to 14 and greater than 15 days groups.

Multivariate regression analysis showed that delayed timing of surgery between 3 and 7 days was protective for postoperative stroke/death (P = 0.003) and any postoperative complication (P = 0.028). Delaying surgery to more than 8 days after stroke was protective for postoperative stroke/death (P < 0.001), postoperative stroke (P < 0.001), and any postoperative complication (P < 0.001).

Conclusions:

Carotid revascularization should occur no sooner than 48 hours after index stroke event. Surgeons should strive to operate between 8 and 14 days to protect against postoperative stroke/death.
Ensuring Equity, Diversity, and Inclusion in Academic Surgery
Authors: West Michaela A. , Hwang Shelley , Maier Ronald V. , Ahuja Nita , Angelos Peter , Bass Barbara L. , Brasel Karen J. , Chen Herbert , Davis Kimberly A. , Eberlein Timothy J. , Fong Yuman , Greenberg Caprice C. , Lillemoe Keith D. , McCarthy Mary C. , Michelassi Fabrizio , Numann Patricia J. , Parangi Sareh , Reyes Jorge D. , Sanfey Hilary A. , Stain Steven C. , Weigel Ronald J. , Wren Sherry M.
Published: July 2018

Objective:

The leadership of the American Surgical Association (ASA) appointed a Task Force to objectively address issues related to equity, diversity, and inclusion with the discipline of academic surgery.

Summary of Background Data:

Surgeons and the discipline of surgery, particularly academic surgery, have a tradition of leadership both in medicine and society. Currently, we are being challenged to harness our innate curiosity, hard work, and perseverance to address the historically significant deficiencies within our field in the areas of diversity, equity, and inclusion.

Methods:

The ASA leadership requested members to volunteer to serve on a Task Force to comprehensively address equity, diversity, and inclusion in academic surgery. Nine work groups reviewed the current literature, performed primary qualitative interviews, and distilled available guidelines and published primary source materials. A work product was created and published on the ASA Website and made available to the public. The full work product was summarized into this White Paper.

Results:

The ASA has produced a handbook entitled: Ensuring Equity, Diversity, and Inclusion in Academic Surgery, which identifies issues and challenges, and develops a set of solutions and benchmarks to aid the academic surgical community in achieving these goals.

Conclusion:

Surgery must identify areas for improvement and work iteratively to address and correct past deficiencies. This requires honest and ongoing identification and correction of implicit and explicit biases. Increasing diversity in our departments, residencies, and universities will improve patient care, enhance productivity, augment community connections, and achieve our most fundamental ambition—doing good for our patients.
Insurance Status Biases Trauma-system Utilization and Appropriate Interfacility Transfer
Authors: Zogg Cheryl K. , Schuster Kevin M. , Maung Adrian A. , Davis Kimberly A.
Published: July 2018

Objective:

To identify the association between insurance status and the probability of emergency department admission versus transfer for patients with major injuries (Injury Severity Score >15) and other complex trauma likely to require higher-level trauma center (TC) care across the spectrum of TC care.

Background:

Trauma systems were developed to facilitate direct transport and transfer of patients with major/complex traumatic injuries to designated TCs. Emerging literature suggests that uninsured patients are more likely to be transferred.

Methods:

Nationally weighted Nationwide Emergency Department Sample (2010–2014) and longitudinal California State Inpatient Databases/State Emergency Department Databases (2009–2011) data identified adult (18–64 yr), pediatric (≤17 yr), and older adult (≥65 yr) trauma patients. Risk-adjusted multilevel (mixed-effects) logistic regression determined differences in the relative odds of direct admission versus transfer and outcome measures based on initial level of TC presentation.

Results:

In all 3 age groups, insured patients were more likely to be admitted [eg, nontrauma center (NTC) private vs uninsured odds ratio (95% confidence interval): adult 1.54 (1.40–1.70), pediatric 1.95(1.45–2.61)]. The trend persisted within levels III and II TCs (eg, level II private vs uninsured adult 1.83 (1.30–2.57)] and among other forms of trauma likely to require transfer. At the state level, among transferred NTC patients, 28.5% (adult), 34.1% (pediatric), and 39.5% (older adult) of patients with major injuries were not transferred to level I/II TCs. An additional 44.3% (adult), 50.9% (pediatric), and 57.6% (older adult) of all NTC patients were never transferred. Directly admitted patients experienced higher morbidity [adult: 19.6% vs 8.2%, odds ratio (95% confidence interval):2.74 (2.17–3.46)] and mortality [3.3% vs 1.8%, 1.85 (1.13–3.04)].

Conclusions:

Insured patients with significant injuries initially evaluated at NTCs and level III/II TCs were less likely to be transferred. Such a finding appears to result in less optimal trauma care for better-insured patients and questions the success of transfer-guideline implementation.
A Prospective Observational Study of Hypogammaglobulinemia in the First Year After Lung Transplantation
Authors: Petrov Andrej A. , Traister Russell S. , Crespo Maria M. , Silveira Fernanda P. , Xie Maylene , Coffey Kara , Ensor Christopher R. , Landsittel Douglass , Pilewski Joseph M.
Published: July 2018

Background

Immunosuppressive therapies have led to improved survival for lung transplant (LT) recipients but these therapies can lead to hypogammaglobulinemia (HGG) and potentially an increased risk of infection. Large prospective studies have not been performed to evaluate the impact of HGG on outcomes for LT recipients.

Methods

This is a single-center prospective observational study of LT recipients. Pretransplant and posttransplant IgG levels were measured and related to infection, rejection, antibiotic use, and immunosuppression use.

Results

One hundred thirty-three LT recipients were prospectively evaluated. Pretransplant IgG values were higher than IgG values at the time of transplant or any time thereafter (all P < 0.0001). Severe HGG (IgG < 400 mg/dL) was highest at the time of transplant (32.4%) while at 3, 6, 9, and 12 months posttransplant the prevalence of severe HGG was 7.4%, 7.5%, 8.9%, and 6.3%, respectively. Severe HGG was associated with 2 or more pneumonias (P = 0.0006) and increased number of antibiotic courses (P = 0.003) compared with the subjects without severe HGG. Pretransplant IgG level and less than 30% of pretransplant protective pneumococcal antibody levels were identified as pretransplant risk factors for severe HGG. In multivariate analysis, chronic obstructive pulmonary disease as the underlying disease and the use of basiliximab as the induction agent in conjunction with higher prednisone and mycophenolate dosing were most predictive of severe HGG (P = 0.005), whereas the combination of age, severe HGG and number of acute steroid courses were most predictive of total days of pneumonia (P = 0.0001).

Conclusions

Our large prospective study identifies risk factors for severe HGG after LT and demonstrates that LT recipients with severe HGG are at increased risk for recurrent pneumonias and more antibiotic courses.
Pimavanserin for Psychotic Symptoms in People With Parkinsonism: A Second Chart Review
Authors: Friedman Joseph H.
Published: July 2018

Introduction

Pimavanserin (Pim) is a 5HT2A inverse agonist that is the only Food and Drug Administration–approved treatment for Parkinson disease (PD) psychosis. The published open-label experience is limited.

Methods

This report is a chart review of all patients who were started on the drugs since the one earlier report on 15 patients. All patients were included, whether or not they completed 6 weeks of treatment, the time required for maximum benefit found in the published phase 3 trial.

Results

Twenty-six patients are reported. Three patients had dementia with Lewy bodies; one had an atypical parkinsonism; 22 had PD, including one with schizophrenia and neuroleptic exacerbated, dopamine transporter scan–positive idiopathic PD; and another had PD complicated by strokes. Six stopped before 6 weeks due to adverse effects, including 1 with worsened psychosis. Eighteen completed at least 6 weeks of treatment. Of these, 3 stopped due to lack of efficacy and 3 due to worsened psychosis. Twelve found it helpful. Of the 18 who took Pim for at least 6 weeks, 12 improved and continue to take it.

Conclusions

Almost 50% of parkinsonian patients with psychotic symptoms found Pim to be a useful medication, which they continue to take. Reasons for intolerance varied and were thought to be unrelated to the drug.
Connectivity and network state-dependent recruitment of long-range VIP-GABAergic neurons in the mouse hippocampus
Authors: Francavilla Ruggiero , Villette Vincent , Luo Xiao , Chamberland Simon , Muñoz-Pino Einer , Camiré Olivier , Wagner Kristina , Kis Viktor , Somogyi Peter , Topolnik Lisa
Published: July 2018

GABAergic interneurons in the hippocampus provide for local and long-distance coordination of neurons in functionally connected areas. Vasoactive intestinal peptide-expressing (VIP+) interneurons occupy a distinct niche in circuitry as many of them specialize in innervating GABAergic cells, thus providing network disinhibition. In the CA1 hippocampus, VIP+ interneuron-selective cells target local interneurons. Here, we discovered a novel type of VIP+ neuron whose axon innervates CA1 and also projects to the subiculum (VIP-LRPs). VIP-LRPs showed specific molecular properties and targeted interneurons within the CA1 area but both interneurons and pyramidal cells within subiculum. They were interconnected through gap junctions but demonstrated sparse spike coupling in vitro. In awake mice, VIP-LRPs decreased their activity during theta-run epochs and were more active during quiet wakefulness but not coupled to sharp-wave ripples. Together, the data provide new evidence for VIP interneuron molecular diversity and functional specialization in controlling cell ensembles along the hippocampo-subicular axis.
Next Generation-Targeted Amplicon Sequencing (NG-TAS): An optimised protocol and computational pipeline for cost-effective profiling of circulating tumour DNA
Authors: Gao Meiling , Callari Maurizio , Beddowes Emma , Sammut Stephen-John , Grzelak Marta , Biggs Heather , Jones Linda , Boumertit Abdelhamid , Linn Sabine C , Cortes Javier , Oliveira Mafalda , Baird Richard , Chin Suet-Feung , Caldas Carlos
Published: July 2018

Circulating tumour DNA (ctDNA) detection and monitoring has enormous potential clinical utility in oncology. We describe here a fast, flexible and cost-effective method to profile multiple genes simultaneously in low input cell-free DNA (cfDNA): Next Generation-Targeted Amplicon Sequencing (NG-TAS). We designed a panel of 377 amplicons spanning 20 cancer genes and tested the NG-TAS pipeline using cell-free DNA from two hapmap lymphoblastoid cell lines. NG-TAS consistently detected mutations in cfDNA when mutation allele fraction was >1%. We applied NG-TAS to a clinical cohort of metastatic breast cancer patients, demonstrating its potential in monitoring the disease. The computational pipeline is available at: https://github.com/cclab-brca/NGTAS_pipeline.
SLIC-CAGE: high-resolution transcription start site mapping using nanogram-levels of total RNA
Authors: Cvetesic Nevena , Leitch Harry G. , Borkowska Malgorzata , Müller Ferenc , Carninci Piero , Hajkova Petra , Lenhard Boris
Published: July 2018

Cap analysis of gene expression (CAGE) is a methodology for genome-wide quantitative mapping of mRNA 5’ends to precisely capture transcription start sites at a single nucleotide resolution. In combination with high-throughput sequencing, CAGE has revolutionized our understanding of rules of transcription initiation, led to discovery of new core promoter sequence features and discovered transcription initiation at enhancers genome-wide. The biggest limitation of CAGE is that even the most recently improved version (nAnT-iCAGE) still requires large amounts of total cellular RNA (5 micrograms), preventing its application to scarce biological samples such as those from early embryonic development or rare cell types. Here, we present SLIC-CAGE, a Super-Low Input Carrier-CAGE approach to capture 5’ends of RNA polymerase II transcripts from as little as 5-10 ng of total RNA. The dramatic increase in sensitivity is achieved by specially designed, selectively degradable carrier RNA. We demonstrate the ability of SLIC-CAGE to generate data for genome-wide promoterome with 1000-fold less material than required by existing CAGE methods by generating a complex, high quality library from mouse embryonic day (E) 11.5 primordial germ cells.
CNTN5−/+orEHMT2−/+iPSC-Derived Neurons from Individuals with Autism Develop Hyperactive Neuronal Networks
Authors: Deneault Eric , Faheem Muhammad , White Sean H. , Rodrigues Deivid C. , Sun Song , Wei Wei , Piekna Alina , Thompson Tadeo , Howe Jennifer L. , Chalil Leon , Kwan Vickie , Walker Susan , Pasceri Peter , Roth Frederick P. , Yuen Ryan K.C. , Singh Karun K. , Ellis James , Scherer Stephen W.
Published: July 2018

Induced pluripotent stem cell (iPSC)-derived cortical neurons are increasingly used as a model to study developmental aspects of Autism Spectrum Disorder (ASD), which is clinically and genetically heterogeneous. To study the complex relationship of rare (penetrant) variant(s) and common (weaker) polygenic risk variant(s) to ASD, “isogenic” iPSC-derived neurons from probands and family-based controls, for modeling, is critical. We developed a standardized set of procedures, designed to control for heterogeneity in reprogramming and differentiation, and generated 53 different iPSC-derived glutamatergic neuronal lines from 25 participants from 12 unrelated families with ASD (14 ASD-affected individuals, 3 unaffected siblings, 8 unaffected parents). Heterozygousde novo(7 families; 16p11.2,NRXN1,DLGAP2,CAPRIN1,VIP,ANOS1,THRA) and rare-inherited (2 families;CNTN5,AGBL4) presumed-damaging variants were characterized in ASD risk genes/loci. In three additional families, functional candidates for ASD (SET), and combinations of putative etiologic variants (GLI3/KIF21AandEHMT2/UBE2Icombinations in separate families), were modeled. We used a large-scale multi-electrode array (MEA) as our primary high-throughput phenotyping assay, followed by patch clamp recordings. Our most compelling new results revealed a consistent spontaneous network hyperactivity in neurons deficient forCNTN5orEHMT2.Our biobank of iPSC-derived neurons and accompanying genomic data are available to accelerate ASD research.