bluuebunny/crossref_metadata_2025 huggingface dataset:
Modularity in Protein Evolution: Modular Organization and De Novo Domain Evolution in Mollusk Metallothioneins
Authors: Calatayud Sara , Garcia-Risco Mario , Pedrini-Martha Veronika , Eernisse Douglas J , Dallinger Reinhard , Palacios Òscar , Capdevila Mercè , Albalat Ricard
Published: September 2020

Metallothioneins (MTs) are proteins devoted to the control of metal homeostasis and detoxification, and therefore, MTs have been crucial for the adaptation of the living beings to variable situations of metal bioavailability. The evolution of MTs is, however, not yet fully understood, and to provide new insights into it, we have investigated the MTs in the diverse classes of Mollusks. We have shown that most molluskan MTs are bimodular proteins that combine six domains—α, β1, β2, β3, γ, and δ—in a lineage-specific manner. We have functionally characterized the Neritimorpha β3β1 and the Patellogastropoda γβ1 MTs, demonstrating the metal-binding capacity of the new γ domain. Our results have revealed a modular organization of mollusk MT, whose evolution has been impacted by duplication, loss, and de novo emergence of domains. MTs represent a paradigmatic example of modular evolution probably driven by the structural and functional requirements of metal binding.
Periphilin self-association underpins epigenetic silencing by the HUSH complex
Authors: Prigozhin Daniil M , Douse Christopher H , Farleigh Laura E , Albecka Anna , Tchasovnikarova Iva A , Timms Richard T , Oda Shun-ichiro , Adolf Frank , Freund Stefan M V , Maslen Sarah , Lehner Paul J , Modis Yorgo
Published: September 2020

Transcription of integrated DNA from viruses or transposable elements is tightly regulated to prevent pathogenesis. The Human Silencing Hub (HUSH), composed of Periphilin, TASOR and MPP8, silences transcriptionally active viral and endogenous transgenes. HUSH recruits effectors that alter the epigenetic landscape and chromatin structure, but how HUSH recognizes target loci and represses their expression remains unclear. We identify the physicochemical properties of Periphilin necessary for HUSH assembly and silencing. A disordered N-terminal domain (NTD) and structured C-terminal domain are essential for silencing. A crystal structure of the Periphilin-TASOR minimal core complex shows Periphilin forms an α-helical homodimer, bound by a single TASOR molecule. The NTD forms insoluble aggregates through an arginine/tyrosine-rich sequence reminiscent of low-complexity regions from self-associating RNA-binding proteins. Residues required for TASOR binding and aggregation were required for HUSH-dependent silencing and genome-wide deposition of repressive mark H3K9me3. The NTD was functionally complemented by low-complexity regions from certain RNA-binding proteins and proteins that form condensates or fibrils. Our work suggests the associative properties of Periphilin promote HUSH aggregation at target loci.
Increased epithelial membrane protein 2 expression in glioblastoma after treatment with bevacizumab
Authors: Patel Kunal S , Kejriwal Sameer , Thammachantha Samasuk , Duong Courtney , Murillo Adrian , Gordon Lynn K , Cloughesy Timothy F , Liau Linda , Yong William , Yang Isaac , Wadehra Madhuri
Published: September 2020

Background

Antiangiogenic therapy with bevacizumab has failed to provide substantial gains in overall survival. Epithelial membrane protein 2 (EMP2) is a cell surface protein that has been previously shown to be expressed in glioblastoma, correlate with poor survival, and regulate neoangiogenesis in cell lines. Thus, the relationship between bevacizumab and EMP2 was investigated.

Methods

Tumor samples were obtained from 12 patients with newly diagnosed glioblastoma at 2 time points: (1) during the initial surgery and (2) during a subsequent surgery following disease recurrence post-bevacizumab treatment. Clinical characteristics and survival data from these patients were collected, and tumor samples were stained for EMP2 expression. The IVY Glioblastoma Atlas Project database was used to evaluate EMP2 expression levels in 270 samples by differing histological areas of the tumor.

Results

Patients with high EMP2 staining at initial diagnosis had decreased progression-free and overall survival after bevacizumab (median progression-free survival 4.6 months vs 5.9 months; log-rank P = .076 and overall survival 7.7 months vs 14.4 months; log-rank P = .011). There was increased EMP2 staining in samples obtained after bevacizumab treatment in both unpaired (mean H-score 2.31 vs 1.76; P = .006) and paired analyses (mean difference 0.571; P = .019). This expression increase correlated with length of bevacizumab therapy (R2  = 0.449; Pearson P = .024).

Conclusions

Bevacizumab treatment increased EMP2 protein expression. This increase in EMP2 correlated with reduced mean survival time post-bevacizumab therapy. We hypothesize a role of EMP2 in clinical bevacizumab resistance and as a potential antiangiogenic therapeutic target in glioblastoma.
Controlled direct synthesis of single- to multiple-layer MWW zeolite
Authors: Chen Jie-Qiong , Li Yu-Zhao , Hao Qing-Qing , Chen Huiyong , Liu Zhao-Tie , Dai Chengyi , Zhang Jianbo , Ma Xiaoxun , Liu Zhong-Wen
Published: September 2020

The minimized diffusion limitation and completely exposed strong acid sites of the ultrathin zeolites make it an industrially important catalyst especially for converting bulky molecules. However, the structure-controlled and large-scale synthesis of the material is still a challenge. In this work, the direct synthesis of the single-layer MWW zeolite was demonstrated by using hexamethyleneimine and amphiphilic organosilane as structure-directing agents. Characterization results confirmed the formation of the single-layer MWW zeolite with high crystallinity and excellent thermal/hydrothermal stability. The formation mechanism was rigorously revealed as the balanced rates between the nucleation/growth of the MWW nanocrystals and the incorporation of the organosilane into the MWW unit cell, which is further supported by the formation of MWW nanosheets with tunable thickness via simply changing synthesis conditions. The commercially available reagents, well-controlled structure and the high catalytic stability for the alkylation of benzene with 1-dodecene make it an industrially important catalyst.
A scoping review of social and behavioral science research to translate genomic discoveries into population health impact
Authors: Allen Caitlin G , Peterson Shenita , Khoury Muin J , Brody Lawrence C , McBride Colleen M
Published: September 2020

Since the completion of the Human Genome Project, progress toward translating genomic research discoveries to address population health issues has been limited. Several meetings of social and behavioral scientists have outlined priority research areas where advancement of translational research could increase population health benefits of genomic discoveries. In this review, we track the pace of progress, study size and design, and focus of genomics translational research from 2012 to 2018 and its concordance with five social and behavioral science recommended priorities. We conducted a review of the literature following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Guidelines for Scoping Reviews. Steps involved completing a search in five databases and a hand search of bibliographies of relevant literature. Our search (from 2012 to 2018) yielded 4,538 unique studies; 117 were included in the final analyses. Two coders extracted data including items from the PICOTS framework. Analysis included descriptive statistics to help identify trends in pace, study size and design, and translational priority area. Among the 117 studies included in our final sample, nearly half focused on genomics applications that have evidence to support translation or implementation into practice (Centers for Disease Control and Prevention Tier 1 applications). Common study designs were cross-sectional (40.2%) and qualitative (24.8%), with average sample sizes of 716 across all studies. Most often, studies addressed public understanding of genetics and genomics (33.3%), risk communication (29.1%), and intervention development and testing of interventions to promote behavior change (19.7%). The number of studies that address social and behavioral science priority areas is extremely limited and the pace of this research continues to lag behind basic science advances. Much of the research identified in this review is descriptive and related to public understanding, risk communication, and intervention development and testing of interventions to promote behavior change. The field has been slow to develop and evaluate public health-friendly interventions and test implementation approaches that could enable health benefits and equitable access to genomic discoveries. As the completion of the human genome approaches its 20th anniversary, full engagement of transdisciplinary efforts to address translation challenges will be required to close this gap.
Creating a Framework to Integrate Residency Program and Medical Center Approaches to Quality Improvement and Patient Safety Training
Authors: Chen Anders , Wolpaw Benjamin J. , Vande Vusse Lisa K. , Wu Chenwei , Meo Nicholas , Staub Milner B. , Hicks Katherine G. , Carr Stephanie A. , Schleyer Anneliese M. , Harrington Robert D. , Klein Jared W.
Published: September 2020

Quality improvement and patient safety (QIPS) are core components of graduate medical education (GME). Training programs and affiliated medical centers must partner to create an environment in which trainees can learn while meaningfully contributing to QIPS efforts, to further the shared goal of improving patient care. Numerous challenges have been identified in the literature, including lack of resources, lack of faculty expertise, and siloed QIPS programs. In this article, the authors describe a framework for integrated QIPS training for residents in the University of Washington Internal Medicine Residency Program, beginning in 2014 with the creation of a dedicated QIPS chief resident position and assistant program director for health systems position, the building of a formal curriculum, and integration with medical center QIPS efforts. The postgraduate year (PGY) 1 curriculum focused on the culture of patient safety and entering traditional patient safety event (PSE) reports. The PGY-2 curriculum highlighted QIPS methodology and how to conduct mentored PSE reviews of cases that were of educational value to trainees and a clinical priority to the medical center. Additional PGY-2/PGY-3 training focused on the active report, presentation, and evaluation of cases during morbidity and mortality conferences while on clinical services, as well as how to lead longitudinal QIPS work. Select residents led mentored QI projects as part of an additional elective. The hallmark feature of this framework was the depth of integration with medical center priorities, which maximized educational and operational value. Evaluation of the program demonstrated improved attitudes, knowledge, and behavior changes in trainees, and significant contributions to medical center QIPS work. This specialty-agnostic framework allowed for training program and medical center integration, as well as horizontal integration across GME specialties, and can be a model for other institutions.
Harnessing the Power of Residents as Change Agents in Quality Improvement
Authors: Lam Philip W. , Wong Brian M.
Published: September 2020

Residency training represents a unique period when learners begin to personally experience the patient safety and quality-of-care issues that affect health care systems and increasingly take responsibility to address them. Their integration into the clinical workflow in clinics, wards, and operating rooms positions them perfectly to observe and characterize the underlying processes that contribute to patient safety and health care quality problems. Residents’ practices and perspectives are less entrenched than those of their faculty counterparts, which enables them to offer fresh ideas on the quality improvement (QI) process. Their creativity and ingenuity serve as assets when coming up with new and innovative changes to test using rapid change cycles. As such, they are ideally suited to serve as health systems change agents.

Training programs and clinical institutions typically see residents as frontline care providers whose primary role is to treat the patient in front of them. Yet, by enabling residents to “treat the system” through QI work, they can take on the role of residents as change agents, which has the potential to have long-lasting effects on patient care on a much wider scale. However, training programs must do more than simply harness residents’ enthusiasm and root them on from the sidelines. Instead, they must create an environment that is conducive to successfully implementing changes at the curricular, institutional, and health systems levels.
Implementation of Changes to Medical Student Documentation at Duke University Health System: Balancing Education With Service
Authors: Gagliardi Jane P. , Bonanno Brian , McPeek Hinz Eugenia R. , Musser R. Clayton , Knudsen Nancy W. , Palko Michael , McNair Felice , Lee Hui-Jie , Clay Alison S.
Published: September 2020

Purpose

When the Centers for Medicare and Medicaid Services (CMS) changed policies about medical student documentation, students with proper supervision may now document their history, physical exam, and medical decision making in the electronic health record (EHR) for billable encounters. Since documentation is a core entrustable professional activity for medical students, the authors sought to evaluate student opportunities for documentation and feedback across and between clerkships.

Method

In February 2018, a multidisciplinary workgroup was formed to implement student documentation at Duke University Health System, including educating trainees and supervisors, tracking EHR usage, and enforcing CMS compliance. From August 2018 to August 2019, locations and types of student-involved services (student–faculty or student–resident–faculty) were tracked using billing data from attestation statements. Student end-of-clerkship evaluations included opportunity for documentation and receipt of feedback. Since documentation was not allowed before August 2018, it was not possible to compare with prior student experiences.

Results

In the first half of the academic year, 6,972 patient encounters were billed as student-involved services, 52% (n = 3,612) in the inpatient setting and 47% (n = 3,257) in the outpatient setting. Most (74%) of the inpatient encounters also involved residents, and most (92%) of outpatient encounters were student–teaching physician only.

Approximately 90% of students indicated having had opportunity to document in the EHR across clerkships, except for procedure-based clerkships such as surgery and obstetrics. Receipt of feedback was present along with opportunity for documentation more than 85% of the time on services using evaluation and management coding. Most students (> 90%) viewed their documentation as having a moderate or high impact on patient care.

Conclusions

Changes to student documentation were successfully implemented and adopted; changes met both compliance and education needs within the health system without resulting in potential abuses of student work for service.
Social Accountability Frameworks and Their Implications for Medical Education and Program Evaluation: A Narrative Review
Authors: Barber Cassandra , van der Vleuten Cees , Leppink Jimmie , Chahine Saad
Published: September 2020

Purpose

Medical schools face growing pressures to produce stronger evidence of their social accountability, but measuring social accountability remains a global challenge. This narrative review aimed to identify and document common themes and indicators across large-scale social accountability frameworks to facilitate development of initial operational constructs to evaluate social accountability in medical education.

Method

The authors searched 5 electronic databases and platforms and the World Wide Web to identify social accountability frameworks applicable to medical education, with a focus on medical schools. English-language, peer-reviewed documents published between 1990 and March 2019 were eligible for inclusion. Primary source social accountability frameworks that represented foundational values, principles, and parameters and were cited in subsequent papers to conceptualize social accountability were included in the analysis. Thematic synthesis was used to describe common elements across included frameworks. Descriptive themes were characterized using the context–input–process–product (CIPP) evaluation model as an organizational framework.

Results

From the initial sample of 33 documents, 4 key social accountability frameworks were selected and analyzed. Six themes (with subthemes) emerged across frameworks, including shared values (core social values of relevance, quality, effectiveness, and equity; professionalism; academic freedom and clinical autonomy) and 5 indicators related to the CIPP model: context (mission statements, community partnerships, active contributions to health care policy); inputs (diversity/equity in recruitment/selection, community population health profiles); processes (curricular activities, community-based clinical training opportunities/learning exposures); products (physician resource planning, quality assurance, program evaluation and accreditation); and impacts (overall improvement in community health outcomes, reduction/prevention of health risks, morbidity/mortality of community diseases).

Conclusions

As more emphasis is placed on social accountability of medical schools, it is imperative to shift focus from educational inputs and processes to educational products and impacts. A way to begin to establish links between inputs, products, and impacts is by using the CIPP evaluation model.
Buprenorphine Induction in Persons With Opioid Use Disorder Hospitalized with Acute Hepatitis A
Authors: Oller Devin A. , Thornton Chase , Nuzzo Paul A. , Fanucchi Laura C.
Published: September 2020

Background:

It is not known whether buprenorphine/naloxone (bup/nx) can be safely initiated in hospitalized patients with acute hepatitis A infection. We assessed liver function and tolerability of bup/nx induction in patients with acute Hepatitis A Virus (HAV).

Methods:

Retrospective review of patients (N = 31) admitted to a tertiary care facility for acute HAV who were evaluated by an addiction medicine consultant.

Results:

No significant difference was seen in aspartate aminotransferase, alanine aminotransferase, total bilirubin, or INR trends in patients receiving bup/nx during hospitalization versus those not receiving bup/nx. Nausea was the most common reported symptom in patients receiving bup/nx.

Discussion and Conclusions:

With careful monitoring and induction dose adjustment, bup/nx can be administered to patients with acute HAV without hepatic encephalopathy. Similarly, patients on bup/nx before hospitalization should not have this medication held in the setting of acute HAV.

Scientific Significance:

This strategy may engage patients with acute HAV in treatment of OUD earlier and minimize disruptions in treatment.
The Changing Landscape of Alcohol Use and Alcohol Use Disorder During the COVID-19 Pandemic - Perspectives of Early Career Professionals in 16 Countries
Authors: Calvey Tanya , Scheibein Florian , Saad Noha Ahmed , Shirasaka Tomohiro , Dannatt Lisa , Stowe MJ , Shah Bigya , Narasimha Venkata Lakshmi , Bruschi Angelo , Peyron Eric , Gumikiriza-Onoria Joy Louise , Ghosh Abhishek , Pant Sagun Ballav , Yee Anne , Ratta-apha Woraphat , Vadivel Ramyadarshni , Siste Kristiana , Maiti Tanay , Boujraf Saïd , Grandinetti Paolo , Morgan Nirvana , Arya Sidharth
Published: September 2020

Alcohol use is a major risk factor for infectious disease and reduction of harms associated with alcohol consumption are essential during times of humanitarian crises, such as the COVID-19 pandemic. As a network of early career professionals working in the area of addiction medicine, we provide our views with regards to national actions related to reducing alcohol-related harm and providing care for people with alcohol use disorder during COVID-19. We believe that COVID-19 related measures have affected alcohol consumption in the majority of countries represented in this commentary. Examples of these changes include changes in alcohol consumption patterns, increases in cases of alcohol withdrawal syndrome, disruptions in access to medical care for alcohol use disorder and increases in illegal production of alcohol. Our members urge that treatment for acute and severe conditions due to substance use should be considered as essential services in times of humanitarian crises like COVID-19.
Factors Associated With Serum Estradiol Levels Among Postmenopausal Women Using Hormone Therapy
Authors: Sriprasert Intira , Kono Naoko , Karim Roksana , Hodis Howard N. , Stanczyk Frank Z. , Shoupe Donna , Mack Wendy J.
Published: September 2020

OBJECTIVE:

To identify factors associated with serum estradiol (E2) levels among healthy postmenopausal women using hormone therapy (HT).

METHODS:

This is an unplanned post hoc analysis of data from ELITE (Early versus Late Intervention Trial with Estradiol), a randomized controlled trial of 1 mg oral E2 with or without vaginal progesterone in healthy early compared with late (<6 years compared with 10 or more years since menopause) postmenopausal women. We included results from visits when women reported at least 80% compliance with HT. Mixed-effects linear models identified factors associated with serum E2 levels while participants were taking HT, assessed every 6 months over a median follow-up of 4.8 years and adjusted for baseline E2 level, visit, and reduced E2 dose. Possible correlates evaluated included demographics, clinical characteristics, medication use, and biomarkers of liver and kidney metabolic function.

RESULTS:

The analysis included 2,160 E2 measurements in 275 postmenopausal women. Mean±SD age was 55.4±3.9 vs 64.4±5.5 years, and mean±SD time since menopause was 3.6±1.8 vs 16.0±5.6 years for early vs late postmenopausal women. Adjusted for pretreatment E2 level, visit, and reduced dose indicator, higher serum E2 levels were associated with higher body mass index (BMI), higher weight, surgical menopause, alcohol use, and antihypertensive medication use. Current and past smoking and antifungal medication use were associated with lower serum E2 levels. In the multivariable model, higher BMI and alcohol use were associated with higher serum E2 levels, whereas current and past smoking were associated with lower serum E2 levels. These factors were similar between early and late postmenopausal women.

CONCLUSION:

Factors associated with serum E2 levels among postmenopausal women taking HT include BMI, alcohol use, and smoking. As serum E2 levels relate to HT effect, achievement of desirable E2 levels may be maximized through personalized intervention.

CLINICAL TRIAL REGISTRATION:

ClinicalTrials.gov, NCT00114517.
Pathophysiologic Origins of Brachial Plexus Injury
Authors: Johnson Grace J. , Denning Stacie , Clark Steven L. , Davidson Christina
Published: September 2020

OBJECTIVE:

To analyze the origins and consequences of cases of brachial plexus injuries and their relationship to shoulder dystocia.

METHODS:

We conducted a retrospective cohort study and identified all neonates with brachial plexus injury delivered at our institution between March 2012 and July 2019. A review was performed of the maternal and neonatal records of each neonate to identify obstetric antecedents, including the occurrence of shoulder dystocia and persistence of the injury. Experience of the delivering clinician was also examined. Statistical analysis was performed with the Fisher exact test, χ2 test for trends, and two-tailed t tests.

RESULTS:

Thirty-three cases of brachial plexus injury were identified in 41,525 deliveries (0.08%). Fourteen (42%) of these cases were not associated with shoulder dystocia; three (9%) followed cesarean delivery. Brachial plexus injury without shoulder dystocia was related to the absence of maternal diabetes, lower birth weights, and a longer second stage of labor. Persistent brachial plexus injury at the time of discharge was seen with equal frequency among neonates with (17/19, 89%, 95% CI 0.52–100%) and without shoulder dystocia (10/14, 71%, 95% CI 34–100%), P=.36). Whether brachial plexus injury was transient or persistent after shoulder dystocia was unrelated to the years of experience of the delivering clinician. Despite ongoing training and simulation, the already low incidence of brachial plexus injury did not decrease over time at our institution.

CONCLUSION:

Brachial plexus injury and shoulder dystocia represent two complications of uterine forces driving a fetus through the maternal pelvis in the presence of disproportion between the passage and the shoulder girdle of the passenger. Either or both of these complications may occur, but often are not causally related.
Intrauterine Vacuum-Induced Hemorrhage-Control Device for Rapid Treatment of Postpartum Hemorrhage
Authors: D’Alton Mary E. , Rood Kara M. , Smid Marcela C. , Simhan Hyagriv N. , Skupski Daniel W. , Subramaniam Akila , Gibson Kelly S. , Rosen Todd , Clark Shannon M. , Dudley Donald , Iqbal Sara N. , Paglia Michael J. , Duzyj Christina M. , Chien Edward K. , Gibbins Karen J. , Wine Kathryn D. , Bentum Nana Ama A. , Kominiarek Michelle A. , Tuuli Methodius G. , Goffman Dena
Published: September 2020

OBJECTIVE:

To evaluate the effectiveness and safety of an intrauterine vacuum-induced hemorrhage-control device for postpartum hemorrhage treatment.

METHODS:

A multicenter, prospective, single-arm treatment study of a novel intrauterine device that uses low-level vacuum to induce uterine myometrial contraction to achieve control of abnormal postpartum uterine bleeding and postpartum hemorrhage was undertaken at 12 centers in the United States. The primary effectiveness endpoint was the proportion of participants in whom use of the intrauterine vacuum-induced hemorrhage-control device controlled abnormal bleeding without requiring escalating interventions. The primary safety endpoint was the incidence, severity, and seriousness of device-related adverse events. Secondary outcomes included time to bleeding control, rate of transfusion, and device usability scored by each investigator using the device.

RESULTS:

Of 107 participants enrolled with primary postpartum hemorrhage or abnormal postpartum uterine bleeding, 106 received any study treatment with the device connected to vacuum, and successful treatment was observed in 94% (100/106, 95% CI 88–98%) of these participants. In those 100 participants, definitive control of abnormal bleeding was reported in a median of 3 minutes (interquartile range 2.0–5.0) after connection to vacuum. Eight adverse events deemed possibly related to the device or procedure were reported, all of which were outlined as risks in the study and all of which resolved with treatment without serious clinical sequelae. Transfusion of 1–3 units of red blood cells was required in 35 participants, and five participants required 4 or more units of red blood cells. The majority of investigators reported the intrauterine vacuum-induced hemorrhage-control device as easy to use (98%) and would recommend it (97%).

CONCLUSION:

Intrauterine vacuum-induced hemorrhage control may provide a new rapid and effective treatment option for abnormal postpartum uterine bleeding or postpartum hemorrhage, with the potential to prevent severe maternal morbidity and mortality.

FUNDING SOURCE:

Alydia Health, Inc.

CLINICAL TRIAL REGISTRATION:

ClinicalTrials.gov, NCT02883673.
Characterization of a Novel Entity of G3 (High-grade Well-differentiated) Colorectal Neuroendocrine Tumors (NET) in the SEER Database
Authors: Punekar Salman R. , Kaakour Dalia , Masri-Lavine Lena , Hajdu Cristina , Newman Elliot , Becker Daniel J.
Published: September 2020

Objectives:

Small studies suggest that a new entity of high-grade (HG) (G3, by Ki-67 or mitotic index) well-differentiated (histologically) gastrointestinal neuroendocrine tumors (NETs) exists, but prognosis and characteristics are unknown. We further characterized demographics and prognosis of patients with colorectal G3 NETs.

Materials and Methods:

We used the Surveillance Epidemiology and End Results (SEER) database to study colorectal NETs diagnosed from 2000 to 2015. We evaluated demographic, clinical, and tumor characteristics. We compared overall survival (OS) for G1-2 NET, G3 NET, and NEC (neuroendocrine carcinoma). We used logistic regression to detect grade associations and Cox proportional hazards models to examine predictors of survival.

Results:

We identified 5894 cases with colorectal NET (5780 [98.1%] G1-2 and 114 [1.9%] G3); the cohort was 66% white, 47% male, and had a median age of 54. Patients with G3 NET were likely to be older (odds ratio [OR]: 2.23; 95% confidence interval [CI]: 1.19-4.19 for 60 to 69 vs. <50), unmarried (OR: 1.56; 95% CI: 1.02-2.38), and less likely to be diagnosed after 2010 (OR: 0.09; 95% CI: 0.06-0.15). OS for G3 NET (median, 36 mo; 95% CI: 13-92) fell between OS for NEC (median, 7 mo; 95% CI: 6-8), and G1-2 NET (median not reached, >120 mo). Among G1-3 NETs, black patients (hazard ratio [HR]: 1.30; 95% CI: 1.03-1.62), older patients (HR: 3.63; 95% CI: 2.63-5.01 for age 60 to 69 vs. <50), unmarried patients (HR: 1.40; 95% CI: 1.17-1.68), and those with HG features (HR: 3.97; 95% CI: 3.15-4.99) had worse survival.

Conclusions:

We defined a subset of G3 NETs that are HG and well differentiated, more common in older, unmarried patients, with a prognosis between that of NEC and G1-2 NETs. Our analysis adds the first national registry study in support of a new classification of nonpancreatic HG and well-differentiated NETs.
Impact of Racial and Gender Variations in Patients With Out-of-hospital Cardiac Arrest: A Nation-Wide Study
Authors: Arunachalam Karuppiah , Zhang Zheng , Chu Antony , Maan Abhishek
Published: September 2020

The overall incidence of Out-of-hospital Cardiac Arrest (OHCA) is decreasing worldwide due to emergency responses, but there are gender and racial differences in the incidence of OHCA, which remain under investigation. Our aim was to identify the incidence, gender, and racial disparities in patients admitted with OHCA. The National Inpatient Sample Database is one of the largest all-payer inpatient database. It was queried to identify patients 18 years or older who were hospitalized with the principal diagnosis of OHCA. There was a total of 85,988 patients who were discharged with a diagnosis classified as OHCA using the ICD-9 code for a period of 2 years. The mean age of the patients who had presented to the hospital with OHCA was 64.3 (±18.5 years). Overall, a greater number of males suffered from OHCA were compared with female population of (48,635 vs 37,366; P < 0.0001). The incidence of OHCA was higher among Caucasians as compared with African Americans (54,812, 63.8% vs 13,787, 16%; P < 0.0001). In-hospital deaths after OHCA were 43,024 (50%). But African Americans had higher mortality than Caucasians after hospitalization for OHCA (adjusted odds ratio, 1.23; 95% confidence interval, 1.18–1.26; P < 0.01). We observed significant differences in gender and racial factors in the patients who were admitted to the hospital with a diagnosis of OHCA based on an analysis of the national inpatient database.
A Computational Fluid Dynamics Study of the Extracorporeal Membrane Oxygenation-Failing Heart Circulation
Authors: Nezami Farhad Rikhtegar , Khodaee Farhan , Edelman Elazer R. , Keller Steven P.
Published: September 2020

Extracorporeal membrane oxygenation (ECMO) is increasingly deployed to provide percutaneous mechanical circulatory support despite incomplete understanding of its complex interactions with the failing heart and its effects on hemodynamics and perfusion. Using an idealized geometry of the aorta and its major branches and a peripherally inserted return cannula terminating in the iliac artery, computational fluid dynamic simulations were performed to (1) quantify perfusion as function of relative ECMO flow and (2) describe the watershed region produced by the collision of antegrade flow from the heart and retrograde ECMO flow. To simulate varying degrees of cardiac failure, ECMO flow as a fraction of systemic perfusion was evaluated at 100%, 90%, 75%, and 50% of total flow with the remainder supplied by the heart calculated from a patient-derived flow waveform. Dynamic boundary conditions were generated with a three-element lumped parameter model to accurately simulate distal perfusion. In profound failure (ECMO providing 90% or more of flow), the watershed region was positioned in the aortic arch with minimal pulsatility observed in the flow to the visceral organs. Modest increases in cardiac flow advanced the watershed region into the thoracic aorta with arch perfusion entirely supplied by the heart.
Long-term Respiratory Extracorporeal Membrane Oxygenation and Prognosis: A Retrospective Analysis
Authors: Bojic Andja , Schellongowski Peter , Robak Oliver , Hermann Alexander , Buchtele Nina , Nagler Bernhard , Lamm Wolfgang , Staudinger Thomas
Published: September 2020

The duration of extracorporeal membrane oxygenation (ECMO) treatments increases, however, data presented from prolonged support is limited. We retrospectively analyzed all patients during a 4-year period undergoing respiratory ECMO for duration of therapy, demographics, therapy-associated parameters, and outcome according to ECMO duration (<28 days and ≥28 days = long-term ECMO). Out of 55 patients undergoing ECMO for ARDS or during bridging to lung transplantation, 18 were on ECMO for ≥28 days (33%). In the long-term group, median ECMO run time was 40 days (interquartile range 34–54 days). Hospital survival was not significantly different between the groups (54% in short-term and 50% in long-term ECMO patients). There was a significantly higher proportion of patients suffering from malignancy in the group of long-term nonsurvivors. Recovery occurred after more than 40 days on ECMO in 3 patients. The longest ECMO run time in a hospital survivor was 65 days. Duration of ECMO support alone was no prognostic factor and should not represent a basis for decision-making. In patients suffering from malignancy, long-term ECMO support seems to be a factor of adverse prognosis, if not futile.
Abdominal Pain After Pediatric Inflammatory Bowel Disease Diagnosis
Authors: Murphy Lexa K. , Suskind David L. , Qu Pingping , Zhou Chuan , Gashi Kaltrina , Kawamura Joy S. , Palermo Tonya M. ,   ImproveCareNow Pediatric IBD Learning Health System, as stipulated by ICN
Published: September 2020

Objectives:

Although abdominal pain is a hallmark symptom of pediatric inflammatory bowel disease (IBD), limited research has examined pain during the first year after diagnosis. The purpose of the present study is to examine prevalence, predictors, and impact of abdominal pain during the 12 months after pediatric IBD diagnosis using data from the ImproveCareNow (ICN) Network.

Patients and Methods:

Participants consisted of 13,875 youth (age 8–18 years, 44% female, 81% Caucasian) with IBD (65% Crohn's disease; 27% ulcerative colitis, 8% indeterminate colitis) enrolled in the ICN Network with data from clinic visits during the first year after diagnosis (1–22 visits; mean = 3.7). Multivariable mixed effects logistic regression models were conducted to analyze the presence versus the absence of abdominal pain, activity limitations, and decrements in well‐being.

Results:

The percentage of youth reporting abdominal pain decreased significantly during the first year after diagnosis and yet a sizeable group reported continued pain at 12 months (55.9% at diagnosis; 34.0% at 12 months). Multivariable analyses revealed that greater time since diagnosis (odds ratio [OR] = 0.98, P < 0.001), higher disease severity (OR = 11.84, P < 0.001), presence of psychosocial risk factors (OR = 2.33, P = 0.036), and female sex (OR = 1.90, P < 0.010) were significant correlates of continuing abdominal pain. Abdominal pain was significantly associated with decrements in well‐being (OR = 5.11, P < 0.001) as well as limitations in activity (OR = 9.31, P < 0.001), over and above the influence of disease severity.

Conclusions:

Abdominal pain is prevalent and impactful, even when controlling for disease activity, during the first year after pediatric IBD diagnosis. Results from the present study can inform screening and tailored pain management intervention efforts in pediatric IBD.
Moving Beyond the Negative
Authors: Das Akanksha , Clerkin Elise M. , Tolin David F. , Assaf Michal , Diefenbach Gretchen J.
Published: September 2020

Individuals with generalized anxiety disorder (GAD) report poorer quality of life (QOL) than do nonanxious controls. Further, although positive affect (PA) and negative affect (NA) have been shown to predict QOL, no previous literature has tested this relationship in the context of individuals with GAD. In the present study, we evaluated the unique and interactive contributions of PA and NA on QOL within a sample of individuals diagnosed with GAD (N = 50). Specifically, a hierarchical regression was conducted to evaluate the unique contributions of PA, NA, and their interaction on QOL, over and above symptoms of depression. PA and depression symptoms were both significant predictors of QOL, whereas neither the main effect for NA nor the PA × NA interaction was statistically significant. Results suggest that, for those with GAD, PA uniquely contributes to QOL. Strategies to upregulate PA may be a useful treatment target for increasing QOL in individuals with GAD.
Perception of Patient Safety and the Reporting System Between Medical Staffs and Patients in China: A Cross-Sectional Online Study
Authors: Xiang Zhun , Jin Qianying , Gao Xuecheng , Li Xingming , Liu Han , Qiao Kun , Jiang Binshan
Published: September 2020

Objective

This study aimed to understand the perception of patient safety and the reporting system in public in China, and make further recommendations for the optimization of the reporting system of patient safety.

Methods

The following data were collected through an online questionnaire from medical staffs and patients: recognition of patient safety, comments on patient participation, comments on spontaneous reports, attitudes toward the principles of spontaneous reports, and willingness to participate. This information was presented with frequency and percentage with 95% confidence intervals (CIs). Spearman rank correlation was used to evaluate the association of those data.

Results

A total of 27,493 valid questionnaires were collected in this study. The participants who knew patient safety very well, regarded patients as an essential part to enhance patient safety, viewed spontaneous reports helpful, agreed on the 3 principles of voluntariness, anonymity, and nonpunishment of the reporter, and were willing to participate in reporting were accounted for 39.2% (95% CI, 38.6%–39.8%), 31.2% (95% CI, 30.7%–31.8%), 25.2% (95% CI, 24.7%–25.7%), 24.0% (95% CI, 23.5%–24.5%), and 19.9% (95% CI, 19.4%–20.4%), respectively. A moderate positive correlation was observed between comments on spontaneous reports and attitudes toward the principles of spontaneous reports (medical staffs versus patients, r
s = 0.452 versus r
s = 0.439; both, P < 0.01), as well as comments on patient participation and comments on spontaneous reports (medical staffs versus patients, r
s = 0.410 versus r
s = 0.460; both, P < 0.01).

Conclusions

The awareness of patient safety may influence the choices of the other questions subsequently and may affect their voluntariness for safety reports ultimately. Pertinent measures, such as publicity of the relevant concept, simplification of the reporting procedures, and promotion of incentive mechanisms, should be adopted to promote the optimization of the reporting system.
A Keyword Approach to Identify Adverse Events Within Narrative Documents From 4 Italian Institutions
Authors: Piscitelli Antonio , Bevilacqua Luciana , Labella Barbara , Parravicini Elena , Auxilia Francesco
Published: September 2020

Objectives

Existing methods for measuring adverse events in hospitals intercept a restricted number of events. Text mining refers to a range of techniques to extract data from narrative sources. The goal of this study was to evaluate the performance of an automated approach for extracting adverse event keywords from within electronic health records.

Methods

The study involved 4 medical centers in the Region of Lombardy. A starting set of keywords was trained in an iterative process to develop queries for 7 adverse events, including those used by the Agency for Healthcare Research and Quality as patient safety indicators. We calculated positive predictive values of the 7 queries and performed an error analysis to detect reasons for false-positive cases of pulmonary embolism, deep vein thrombosis, and urinary tract infection.

Results

Overall, 397,233 records were collected (34,805 discharge summaries, 292,593 emergency department notes, and 69,835 operation reports). Positive predictive values were higher for postoperative wound dehiscence (83.83%) and urinary tract infection (73.07%), whereas they were lower for deep vein thrombosis (5.37%), pulmonary embolism (13.63%), and postoperative sepsis (12.28%). The most common reasons for false positives were reporting of past events (42.25%), negations (22.80%), and conditions suspected by physicians but not confirmed by a diagnostic test (11.25%).

Conclusions

The results of our study demonstrated the feasibility of using an automated approach to detect multiple adverse events in several data sources. More sophisticated techniques, such as natural language processing, should be tested to evaluate the feasibility of using text mining as a routine method for monitoring adverse events in hospitals.
Prevalence and predictors of bone health among perinatally HIV-infected adolescents
Authors: Mahtab Sana , Scott Chris , Asafu-Agyei Nana Akua A. , Machemedze Takwanisa , Frigati Lisa , Myer Landon , Zar Heather J.
Published: September 2020

Objectives:

Long-term complications of HIV including low bone mineral density remain a concern. We studied the prevalence and predictors of low bone mineral density among South African perinatally HIV-infected adolescents (PHIVA) on antiretroviral therapy (ART).

Design:

Cross-sectional analysis.

Methods:

Bone health was evaluated by measuring the calcaneus stiffness index among PHIVA on ART. Low stiffness index was defined as z-score less than −2 SD compared with age-matched and sex-matched HIV-uninfected adolescents (HIV−).

Result:

Overall, 407 PHIVA (median age: 14 years; 50.4% female; median age at ART initiation: 4.2 years) and 92 HIV− (median age: 13.7 years; 54.4% female) were included. Median duration on ART was 9.8 years (interquartile range 6.8–11.5) with 38% initiating ART at 2 years or less of age. Stiffness index was lower in PHIVA (−0.19 vs. 0.43, P ≤ 0.001), respectively. During puberty, mean stiffness index increased with Tanner Stage in both PHIVA and HIV− but these increases were larger among HIV−; Tanner Stage II–III (96 vs. 101, P = 0.009) and Tanner Stage IV–V (104 vs. 112, P = 0.001). Among PHIVA, 52 (13%) had low stiffness index. After adjusting for age, sex and Tanner Stage, use of lopinavir/ritonavir [odds ratio (OR) = 2.31, P = 0.012] and viral load more than 50 copies/ml (OR = 2.06, P = 0.023) were associated with increased risk of low stiffness index, while use of efavirenz (OR = 0.41, P = 0.009) was associated with decreased risk of low stiffness index.

Conclusion:

Stiffness index was a significantly lower in PHIVA than in HIV−, especially during puberty. Among PHIVA, detectable viral load and use of lopinavir/ritonavir were risk factors for low stiffness index. Further longitudinal studies are important to determine the clinical implications.
Impact of Pneumoperitoneum on the Development of Acute Kidney Injury: Comparison Between Normal and Diabetic Rats
Authors: Abboud Wisam , Bishara Bishara , Nativ Omri , Awad Hoda , Kinaneh Safa , Abu-Salah Niroz
Published: September 2020

Background:

Minimally invasive surgery is considered the gold-standard approach for many surgical procedures. However, it requires CO2 insufflation and elevated intra-abdominal pressure (IAP), which may result in adverse pulmonary, cardiovascular, gastrointestinal, and renal changes. The kidneys are highly sensitive to pressure changes, where risk factors such as severe infection, dehydration, older age, and chronic kidney disease may aggravate the likelihood for the development of acute kidney injury (AKI). Unfortunately, the impact of diabetes mellitus on the deleterious effects of elevated IAP-induced AKI was not fully studied so far. The present study was designed to examine the effect of pneumoperitoneum on renal function and the development of AKI in diabetic rats.

Materials and Methods:

Sprague Dawley rats were divided into 2 groups: control (nondiabetic) rats (n=7) and diabetic rats (n=10). A Veress needle was introduced through the supravesical incision where inflating CO2 allowing the IAP to be increased to the desired pressures 7, 10, and 14 mm Hg for 45 minutes each and at the end of the experiment, the pressure was deflated to zero. During each pressure point, hemodynamic parameters were recorded and urine and blood samples were collected for analysis.

Results:

The baseline values of renal hemodynamic were significantly lower in diabetic rats. There were no major statistically significant changes from baseline in urinary flow, urinary sodium excretion (UNaV), glomerular filtration rate, and renal plasma flow during 7 mm Hg pressure in both groups. When the IAP was further elevated, a significant deterioration of these parameters was recorded. This trend was more pronounced among diabetic rats. When examining urinary neutrophil gelatinase-associated lipocalin, a linear correlation was observed between the IAP and the biomarker level. This correlation was more significant in the diabetic group.

Conclusion:

The present study demonstrated a direct correlation between IAP elevation and the development of AKI. Diabetic rats were more sensitive to the deleterious effect of pneumoperitoneum, where urinary neutrophil gelatinase-associated lipocalin levels may be used as a future biomarker to predict postoperative AKI, especially in patients with diabetes.
Prolapse of Colonic Neovagina After Vaginoplasty for Childhood Rhabdomyosarcoma Treated With Modified Altemeier Procedure
Authors: Fechter Chelsea , Panza Joseph , Hopkins Michael Benjamin , Biller Daniel
Published: September 2020

We present the case of a patient with recurrent sigmoid neovaginal prolapse treated with a modified Altemeier procedure for rectal prolapse, which has not been previously described in the literature.

Our case highlights the difficulty in treating patients with intestinal neovaginal prolapse due to their complex abdominal surgical history, altered anatomy, and goals of care.