bluuebunny/crossref_metadata_2025 huggingface dataset:
In Vitro Screening of a Culturable Soybean Cyst Nematode Cyst Mycobiome for Potential Biological Control Agents and Biopesticides
Authors: Haarith Deepak , Kim Dong-gyu , Strom Noah B. , Chen Senyu , Bushley Kathryn E.
Published: April 2020

Fungal biological control of soybean cyst nematodes (SCN) is an important component of integrated pest management for soybean. However, very few fungal biological control agents are available in the market. In this study, we have screened fungi previously isolated from SCN cysts over 3 years from a long-term crop rotation field experiment for their ability to antagonize SCN using (i) parasitism, (ii) egg hatch inhibition, and (iii) J2 mortality. We evaluated egg parasitism using an in-vitro egg parasitism bioassays and scored parasitism using the egg parasitic index (EPI) and fluorescent microscopy. The ability of these fungi to produce metabolites causing egg hatch inhibition and J2 mortality was assessed in bioassays using filter-sterilized culture filtrates. We identified 10 high-performing isolates each for egg parasitism and toxicity toward SCN eggs and J2s and repeated the tests after storage for 1 year of cryopreservation at −80°C to validate the durability of biocontrol potential of the chosen 20 isolates. Although the parasitic ability changed slightly for the majority of strains after cryopreservation, they still scored 5/10 on EPI scales. There were no differences in the ability of fungi to produce antinemic metabolites after cryopreservation.

[Formula: see text] Copyright © 2020 The Author(s). This is an open access article distributed under the CC BY 4.0 International license .
Health Systems Science in Medical Education: Unifying the Components to Catalyze Transformation
Authors: Gonzalo Jed D. , Chang Anna , Dekhtyar Michael , Starr Stephanie R. , Holmboe Eric , Wolpaw Daniel R.
Published: April 2020

Medical education exists in the service of patients and communities and must continually calibrate its focus to ensure the achievement of these goals. To close gaps in U.S. health outcomes, medical education is steadily evolving to better prepare providers with the knowledge and skills to lead patient- and systems-level improvements. Systems-related competencies, including high-value care, quality improvement, population health, informatics, and systems thinking, are needed to achieve this but are often curricular islands in medical education, dependent on local context, and have lacked a unifying framework. The third pillar of medical education—health systems science (HSS)—complements the basic and clinical sciences and integrates the full range of systems-related competencies. Despite the movement toward HSS, there remains uncertainty and significant inconsistency in the application of HSS concepts and nomenclature within health care and medical education. In this Article, the authors (1) explore the historical context of several key systems-related competency areas; (2) describe HSS and highlight a schema crosswalk between HSS and systems-related national competency recommendations, accreditation standards, national and local curricula, educator recommendations, and textbooks; and (3) articulate 6 rationales for the use and integration of a broad HSS framework within medical education. These rationales include: (1) ensuring core competencies are not marginalized, (2) accounting for related and integrated competencies in curricular design, (3) providing the foundation for comprehensive assessments and evaluations, (4) providing a clear learning pathway for the undergraduate–graduate–workforce continuum, (5) facilitating a shift toward a national standard, and (6) catalyzing a new professional identity as systems citizens. Continued movement toward a cohesive framework will better align the clinical and educational missions by cultivating the next generation of systems-minded health care professionals.
Shaping a Culture for Continuous Quality Improvement in Undergraduate Medical Education
Authors: Bendermacher Guy W.G. , De Grave Willem S. , Wolfhagen Ineke H.A.P. , Dolmans Diana H.J.M. , oude Egbrink Mirjam G.A.
Published: April 2020

Purpose

This study sought to identify key features of an organizational quality culture and explore how these features contribute to continuous quality improvement of undergraduate medical education.

Method

Between July and December 2018, researchers from Maastricht University in the Netherlands conducted a multicenter focus group study among 6 education quality advisory committees. Participants were 22 faculty and 18 student representatives affiliated with 6 medical schools in the Netherlands. The group interviews focused on quality culture characteristics in relation to optimizing educational development, implementation, evaluation, and (further) improvement. Template analysis, a stepwise type of thematic analysis, was applied to analyze the data.

Results

Five main themes resembling quality culture constituents to continuous educational improvement were identified: (1) fostering an open systems perspective, (2) involving stakeholders in educational (re)design, (3) valuing teaching and learning, (4) navigating between ownership and accountability, and (5) building on integrative leadership to overcome tensions inherent in the first 4 themes. A supportive communication climate (which can be fueled by the organization’s leaders) contributes to and is integrated within the first 4 themes.

Conclusions

The results call for a shift away from static quality management approaches with an emphasis on control and accountability toward more flexible, development-oriented approaches focusing on the 5 themes of a culture for continuous quality improvement. The study provides new insights in the link between theory and practice of continuous quality improvement. Specifically, in addition to quality management systems and structures, faculty’s professional autonomy, collaboration with peers and students, and the valuing of teaching and learning need to be amplified.
Five Questions for Residency Leadership in the Time of COVID-19: Reflections of Chief Medical Residents From an Internal Medicine Program
Authors: Rakowsky Shana , Flashner Bess M. , Doolin Jim , Reese Zachary , Shpilsky Jason , Yang Shu , Smith C. Christopher , Graham Kelly
Published: April 2020

The COVID-19 pandemic has drastically affected the traditional methods residency programs use to train their residents. Chief residents serve a unique role as part of the residency leadership to foster the education and development of the residents. Given the rapid shift in demands on physicians in the face of the pandemic, the responsibilities of the chief residents have also shifted to help prepare the residents to meet these demands as frontline providers. There is not a precedent for how residency programs respond to this crisis while maintaining their primary role to develop and train physicians. The authors have identified 5 questions chief residents can ask to guide their program’s response to the demands of COVID-19 during this uncertain time in health care.
Substance Dependence Comorbidity With Mental Disorders in Egyptian Young Adults
Authors: El-Shinnawy Hanan , Sayed Radwa H. , Khalil Mohamed A. , Ayoub Doaa R.
Published: April 2020

Objectives:

Substance dependence is commonly seen among Egyptian young adults. Unfortunately limited data are available about the prevalence of comorbidity of mental disorders and substance dependence in this age group. In addition, substance dependence is correlated with many psychopathologic factors such as low self-esteem, childhood abuse, and stressful life events, etc. which could aggravate the load of the disorder.

Methods:

A case control study that included 80 patients diagnosed with substance dependence according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, text revised (DSM-IV-TR). The sample was recruited from Kasr Al-Ainy Psychiatry and Addiction Hospital. Subjects were divided into 2 groups: group 1 (cases with the diagnosis of comorbid substance dependence and other mental disorder) and group 2 (cases with the diagnosis of substance dependence only). They were examined using Addiction Severity Index (ASI) and Rosenberg Self-Esteem Scale (RES).

Results:

Patients in group 1 had significantly higher levels of impairment and disability in scores of ASI: drug use, social impairment, and psychiatric problems. They had higher percentage of psychopathologic factors, for example, history of childhood abuse. There was no significant difference in the presence of comorbid personality disorder, or history of stressful life events.

Conclusions:

Comorbidity of mental disorders with substance dependence is associated with more impairment and functional deterioration. Young adults with substance dependence have high levels of associated psychopathologic factors, such as childhood abuse, stressful life events, and deliberate self-harm.
RETeval Portable Electroretinogram Parameters in Different Severity Stages of Glaucoma
Authors: Kita Yoshiyuki , Holló Gábor , Saito Tsunehiro , Momota Yousuke , Kita Ritsuko , Tsunoda Kazushige , Hirakata Akito
Published: April 2020

Précis:

Four parameters of the noninvasive, portable RETeval electroretinogram (ERG) system were found to correlate with visual field mean deviation and optical coherence tomography (OCT) thickness parameters, and may therefore be suitable for glaucoma detection.

Purpose:

To investigate the RETeval full-field ERG parameters for accuracy of separating glaucoma and normal eyes, and correlation with glaucoma severity.

Patients and Methods:

Sixty-two eyes of 62 primary open-angle glaucoma patients [visual field mean deviation (MD) range: −0.44 to −31.15 dB] and 39 eyes of 39 healthy controls underwent one RETeval test (photopic negative response protocol), OCT imaging, and Humphrey 30-2 visual field testing. The glaucoma patients were divided into early (MD≥−6dB, n=33) and moderate-to-advanced (MD<−6 dB, n=29) groups.

Results:

Significant correlations were found between the best-performing 4 RETeval ERG parameters and the glaucoma severity measures (MD and OCT thickness parameters) for all eyes, all glaucoma eyes and the moderate-to-advanced glaucoma eyes [photopic negative response amplitude at 72 ms (PhNR 72) and MD: r=−0.333, −0.414, and −0.485, respectively, P≤0.008; PhNR 72 and average circumpapillary retinal nerve fiber layer thickness; r=−0.429, −0.450, and −0.542, respectively, P≤0.002]. Except for P-ratio, there was no significant difference between the area under the receiver-operating characteristic (AUROC) values of the OCT thickness parameters (range: 0.927 to 0.938) and the 4 best-performing RETeval ERG parameters (range: 0.839 to 0.905) in the early glaucoma versus control separation. For differentiating the control and the moderate-to-advanced glaucoma eyes, the AUROC values of the 4 best-performing RETeval ERG parameters ranged between 0.924 and 0.958, and no significant difference was found between them and those of the OCT parameters.

Conclusions:

The noninvasive, portable RETeval full-field ERG device may be useful to detect glaucoma in moderate-to-advanced stages.
Acute Intraocular Pressure Responses to Reading: The Influence of Body Position
Authors: Vera Jesús , Redondo Beatriz , Molina Rubén , Cárdenas David , Jiménez Raimundo
Published: April 2020

Précis:

Greater intraocular pressure (IOP) values are observed when reading in the supine position in comparison with the sitting position, and thus, it should be considered by eye care specialists for the management of glaucoma patients or those at risk.

Purpose:

IOP is sensitive to near work and body position, however, the influence of the body position adopted while performing near tasks remains unknown. This study aimed to assess the IOP changes induced by reading on a smartphone in sitting and supine position, and to explore whether these IOP changes differ between men and women.

Methods:

Twenty-four healthy young adults (12 men and 12 women) read a text on a smartphone placed at 30 cm for 25 minutes while lying down and sitting in 2 different days. A rebound tonometer, which allows assessing IOP in the supine position, was used to measure IOP before reading, during reading (5, 15, and 25 min), and after 5 minutes of recovery. Complementarily, the authors checked the level of sleepiness/alertness before reading, and the perceived levels of fatigue and discomfort after reading.

Results:

The data showed that reading induces an IOP rise [P<0.001, partial eta squared (ηp
2)=0.44]. These effects were more accentuated when reading in the supine position in comparison with the sitting position (P=0.019, ηp
2=0.23) with an increment of 2.4 mm Hg (14%) and 1.3 mm Hg (8%) after 25 minutes of reading, respectively. The IOP rises associated with reading did not differ between men and women (P=0.127). Participants reported greater levels of discomfort in the neck and back when reading in the sitting position (P=0.012, ηp
2=0.25).

Conclusions:

The IOP rises associated with reading are greater when it is performed in the supine position in comparison with the sitting position. The present findings indicate that reading in the supine position should be discouraged in individuals who should avoid IOP increments or fluctuations.
Is Carbon Dioxide Insufflation During Endoscopy in Children as Safe and as Effective as We Think?
Authors: Dike Chinenye R. , Rahhal Riad , Bishop Warren P.
Published: April 2020

Objectives:

Distension of the gastrointestinal lumen is crucial for visualization and advancement during endoscopic procedures. An increasing number of pediatric centers now use carbon dioxide (CO2) preferentially over air as many adult studies and a few pediatric studies have concluded that CO2 is better tolerated than air, especially for colonoscopy.

Aims:

The aim of the study was to determine if CO2 is as safe and as effective as air and if it reduces abdominal discomfort and distension in children undergoing upper endoscopy and colonoscopy.

Methods:

Double blinded, prospective, randomized clinical study. Patient‐ and nursing‐reported outcomes of pain and distension were recorded. End tidal CO2 (EtCO2) was monitored continuously with a CO2‐sampling nasal cannula for patients undergoing procedural sedation and via the endotracheal tube for those who were intubated.

Results:

One hundred seventy‐eight patients with 180 procedures were enrolled, 91 procedures were randomized to receive CO2, and 89 to air. Groups did not differ significantly with respect to nursing‐assessed abdominal discomfort, change in girth from baseline, or endoscopist‐perceived ease of inflation. Use of CO2 was associated with transient spikes in the EtCO2 (≥60 mmHg) in a significant number of patients during sedated upper endoscopy without endotracheal intubation. There was a reduction of bloating and flatulence for all procedures in the CO2 group.

Conclusions:

The benefits of using CO2 for insufflation were minimal in our patients. The observed transient elevations of EtCO2 during sedated upper endoscopy raise concerns of possible systemic hypercarbia. The wisdom of its routine use for all pediatric endoscopic procedures is questioned.
Family‐centered Outcomes that Matter Most to Parents
Authors: Simione Meg , Dartley Anna Nicole , Cooper‐Vince Christine , Martin Victoria , Hartnick Christopher , Taveras Elsie M. , Fiechtner Lauren
Published: April 2020

Objective:

The purpose of this study was to examine the perspectives of caregivers of children with feeding disorders. We sought to understand their child's feeding impairment through the lens of caregivers, including the impact impairments had on daily life and social participation, what outcomes matter most to caregivers, contextual determinants that affect achieving desired outcomes, and how treatment approaches can optimally support families.

Methods:

We interviewed caregivers of children, ages 2 to 5 years, who received care at the Center for Feeding and Nutrition at MassGeneral Hospital for Children in Boston, MA. All children had a feeding disorder diagnosis, defined as an impairment in oral intake. We analyzed interview transcripts using principles of immersion‐crystallization.

Results:

We reached thematic saturation after interviewing 30 caregivers (25 female). 66.7% of the children were white, 13.3% Asian, 10.0% black, and 10.0% were more than 1 race. Thirty percent were Hispanic. We identified four themes: feeding impairments impact the daily life and social participation of children; improving their child's health and quality of life is most important to caregivers; child, caregiver, and community factors are facilitators of achieving desired outcomes; whereas time, financial, access, and knowledge factors are barriers; and caregivers prefer treatment approaches that incorporate principles of family‐centered care.

Conclusions:

Given the daily life and social participation impacts of pediatric feeding disorders, treatment approaches should be family‐centered, focus on functional and meaningful outcomes to improve the health and quality of life of children and their families, and address modifiable sociocontextual determinants.
Routine Screening for Celiac Disease in Children With Down Syndrome Improves Case Finding
Authors: Liu Edwin , Wolter‐Warmerdam Kristine , Marmolejo Juana , Daniels Dee , Prince Garrett , Hickey Fran
Published: April 2020

Objectives:

Children with Down syndrome have an estimated 6‐fold increased risk of developing celiac disease in the United States compared with the general population, yet the determination to screen for celiac disease in this population is not agreed upon. The objectives of this study are to assess the prevalence of celiac disease in children with Down syndrome in our center and compare features from this population identified clinically and through screening.

Methods:

This is a retrospective chart review of 1317 children with Down syndrome who received treatment at a single institution from 2011 to 2017. All participants (n = 90; 53.3% boys) met inclusion criteria of celiac disease diagnosis between 1 month and 22 years of age and Down syndrome. Clinical details were collected, which included the results from celiac disease screening tests, reason for diagnosis and/or testing, symptoms, nutrition notes, demographics, comorbidities, and outcomes.

Results:

Prevalence of celiac disease in our population of children with Down syndrome ages 3 years or older was 9.8%. Mean age at diagnosis was 9.24 years (SD = 4.98) with an average of 2.85 years (SD ± 3.52) lag from the onset of symptoms to diagnosis for children clinically identified in comparison with 1.69 years (SD ± 2.09) for children identified through routine screening. Eighty‐two percentage of clinic patients received a diagnosis of celiac disease because of routine screening compared with clinical testing based on identified symptoms alone.

Conclusion:

Our results suggest the need for routine celiac disease screening in children with Down syndrome to improve case‐finding and avoid diagnostic delay.
Pediatric Endoscopy in the Era of Coronavirus Disease 2019
Authors: Walsh Catharine M. , Fishman Douglas S. , Lerner Diana G. ,   NASPGHAN Endoscopy and Procedures Committee
Published: April 2020

The delivery of endoscopic care is changing rapidly in the era of Coronavirus Disease 2019 (COVID‐19). The North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition (NASPGHAN) Endoscopy and Procedures Committee has formulated this statement to offer practical guidance to help standardize endoscopy services for pediatric patients with the aim of minimizing COVID‐19 transmission to staff, patients, and caregivers and to conserve personal protective equipment (PPE) during this critical time. Appropriate use of PPE is essential to minimize transmission and preserve supply. Pediatric endoscopic procedures are considered at high risk for COVID‐19 transmission. We recommend that all pediatric endoscopic procedures are done in a negative pressure room with all staff using proper airborne, contact, and droplet precautions regardless of patient risk stratification. This includes appropriate use of a filtering face‐piece respirator (N95, N99, FFP2/3, or PAPR), double gloves, facial protection (full visor and/or face shield), full body water‐resistant disposable gown, shoe covers and a hairnet. In deciding which endoscopic procedures should proceed, it is important to weigh the risks and benefits to optimize healthcare delivery and minimize risk. To inform these decisions, we propose a framework for stratifying procedures as emergent (procedures that need to PROCEEED), urgent (PAUSE, weigh the benefits and risks in deciding whether to proceed) and elective (POSTPONE procedures). This statement was based on emerging evidence and is meant as a guide. It is important that all endoscopy facilities where pediatric procedures are performed follow current recommendations from public health agencies within their jurisdiction regarding infection prevention and control of COVID‐19.
A Chinese Boy With Lupus Anticoagulant-hypoprothrombinemia Syndrome: A Case Report and Review of the Literature
Authors: Chan Eugene Yu-Hin , Leung Kate F.S. , Soo Euan T.L. , Ma Alison L.T.
Published: April 2020

We herein report an unusual case of lupus with bleeding diathesis in a Chinese adolescent boy. In the presence of lupus anticoagulant and hypoprothrombinemia, the diagnosis of lupus anticoagulant-hypoprothrombinemia syndrome was made. He responded promptly to immunosuppressive agents and achieved disease remission.
A Novel PUS1 Mutation in 2 Siblings with MLASA Syndrome: A Review of the Literature
Authors: Oncul Ummuhan , Unal-Ince Elif , Kuloglu Zarife , Teber-Tiras Serap , Kaygusuz Gulsah , Eminoglu Fatma T.
Published: April 2020

Myopathy, lactic acidosis, and sideroblastic anemia (MLASA) is a rare mitochondrial disorder characterized by MLASA. Variable features of this condition include failure to thrive, and developmental delay or intellectual disability. Additional symptoms consist of cognitive impairment, skeletal and dental abnormalities, delayed motor milestones, cardiomyopathy, dysphagia, and respiratory insufficiency. MLASA has previously been associated with mutations in pseudouridylate synthase 1 (PUS1) and YARS2. PUS1 encodes the nuclear PUS1 enzyme, which is located in both the nucleus and the mitochondria. PUS1 converts uridine into pseudouridine in several cytosolic and mitochondrial transfer RNA positions and increases the efficiency of protein synthesis in both compartments.

In the present report, we report on 2 Turkish sisters 4 and 11 of years with an MLASA plus phenotype. Both patients have sideroblastic anemia, lactic acidosis, failure to thrive, developmental delay, and chronic diarrhea; in addition, the older sister has strabismus and skeletal anomalies. The sequencing of the PUS1 gene revealed a novel homozygous p.Glu311* mutation. The phenotype of the older sibling is also unique because of the strabismus and skeletal anomalies, when compared with her sister and other previously reported patients with MLASA. The structural differences in the nuclear versus mitochondrial isoforms of PUS1 and modifier genes may be implicated in the variability of the clinical presentations in MLASA.

Conclusion:

This report adds to the growing number of mutations causing complex clinical manifestations of MLASA including lactic acidosis, sideroblastic anemia, chronic diarrhea, and myopathy.
Clinical Utility of Anaerobic and Fungal Blood Cultures in the Pediatric Oncologic Population
Authors: Kumar Madan , Campos Joseph , Hanisch Benjamin
Published: April 2020

Background:

If there is a concern for sepsis in a pediatric patient an aerobic blood culture is obtained. A febrile or ill oncology patient will often be evaluated with aerobic, anaerobic, and fungal blood cultures. There is to our knowledge little evidence to confirm the added benefit of broadly obtaining these cultures.

Methods:

A retrospective analysis of blood cultures from patients in the oncology and hematopoietic stem cell transplant wards at Children’s National Medical Center between January 2010 and April 2017. Positive anaerobic and fungal cultures were evaluated for corollary positive aerobic cultures from the same time frame (+/−24 h). Unique isolates were designated as those positive anaerobic and fungal cultures without positive aerobic cultures and evaluated with detailed chart review.

Results:

A total of 10,950 cultures were evaluated during the study period: 6579 aerobic, 2391 anaerobic cultures, 1980 fungal. In total, 419 positive aerobic, 140 positive anaerobic, and 43 positive fungal cultures were reviewed. Among these, 22 unique anaerobic cultures and 21 unique fungal cultures met case criteria. Only 7 cultures of obligate anaerobes were observed: 4 Clostridial spp., 2 Propionobacterium acnes, and 1 Peptostreptococcus spp. Thirteen of 21 fungal isolates consisted of a single colony and were regarded as probable contaminants. Penicillium, Cladosporium, and dematiaceous molds were in greatest frequency. Potential risk factors for patients with breakthrough isolates were evaluated and described.

Conclusions:

There is little increased yield from the use fungal and anaerobic blood cultures in addition to aerobic blood cultures in the routine evaluation of pediatric oncology and bone marrow transplant patients. Fungal and anaerobic blood cultures and should be reserved for cases with high clinical suspicion.
Quantitative HIV-1-specific antibodies as predictors of peripheral blood cell-associated HIV-1 DNA concentrations
Authors: McManus Margaret , Karalius Brad , Patel Kunjal , Persaud Deborah , Luzuriaga Katherine
Published: April 2020

Objective:

This study evaluated HIV-1 antibody levels as predictors of cell-associated HIV-1 DNA levels in perinatally infected (PHIV) children with long-term viral suppression on antiretroviral therapy (ART).

Design:

HIV-1 antibody and HIV-1 DNA levels were measured in blood specimens from 61 children and adolescents from the Pediatric HIV/AIDS Cohort Study: Adolescent Master Protocol. Twenty perinatally HIV-1-exposed, uninfected children studied through 2 years served as controls.

Methods:

HIV-1 IgG antibodies to six HIV-1 proteins were measured by quantitative ELISA; HIV-1 DNA levels were measured by droplet digital PCR.

Results:

Among 13 children with viral suppression at less than 1 year, antibodies to gp160 and gp41 were low but stable longitudinally; antibodies to p17, p24, and RT decreased, and antibodies to p31 were low or undetectable. Among 48 children with viral suppression between 1 and 5 years, antibody levels to all six HIV-1 proteins were higher than in children with earlier viral suppression and remained high over time. A receiver operator curve approach identified gp41 and gp160 as useful predictors of HIV-1 DNA less than 10 or less than 100 copies per million PBMC (cpm); C-statistics including all antibodies ranged from 0.75 to 0.77. An ensemble learning approach also identified gp41 and gp160 as important predictors of HIV-1 DNA less than 10 or less than 100 cpm; area under the curve estimates utilizing all HIV-1 antibodies ranged from 0.70 to 0.81.

Conclusion:

Quantitative HIV-1 gp41 and gp160 antibody levels may serve as rapid, inexpensive screening tools for low PBMC HIV-1 DNA levels in children with viral suppression on ART, facilitating inclusion into remission protocols.
Psychiatric trajectories across adolescence in perinatally HIV-exposed youth: the role of HIV infection and associations with viral load
Authors: Nguyen Nadia , Choi C. Jean , Robbins Reuben , Korich Rehema , Raymond Jeanette , Dolezal Curtis , Leu Cheng-Shiun , Wiznia Andrew , Abrams Elaine J. , Mellins Claude A.
Published: April 2020

Objective:

Identify factors associated with trajectories of psychiatric disorder among 340 adolescents and young adults (AYA) living with perinatal HIV infection (PHIV) and perinatal HIV-exposure but not infection (PHEU).

Design:

Longitudinal cohort study of AYA in New York City, 9–16 years at enrollment.

Methods:

We used multivariate longitudinal latent class analysis to identify trajectories of psychiatric disorder, and logistic regression to examine predictors of trajectories (e.g. PHIV status) and associations between trajectories and viremia in young adulthood (AYA with PHIV only).

Results:

Among all AYA, we identified three psychiatric trajectories: relatively ‘low disorder’ (63%), ‘consistent anxiety’ (26%), and ‘escalating comorbidity’ (11%). Compared with AYA with ‘low disorder’, AYA with ‘escalating comorbidity’ were significantly older, reported more neighborhood stress, and lived with a caregiver with alcohol use disorder, whereas AYA with ‘consistent anxiety’ were more likely female individuals. Although we found no statistically significant HIV status differences, among AYA with PHIV, nearly half (48%) were viremic in young adulthood, with higher odds of viremia among AYA with ‘escalating comorbidity’ (OR: 3.88, 95% CI: 0.93–16.26) and ‘consistent anxiety’ (OR: 2.41, 95% CI: 1.011–5.75) compared with ‘low disorder’.

Conclusion:

Despite significant adversity, AYA with PHIV and PHEU had relatively low prevalence of psychiatric disorder over time, although one-third had consistent or escalating psychiatric disorders. Among AYA with PHIV, psychiatric trajectories were associated with viremia in young adulthood. Given the growing population of AYA living with PHIV and PHEU worldwide, addressing the substantial and evolving mental health needs of both groups as they reach young adulthood is critical.
Incident infection in high-priority HIV molecular transmission clusters in the United States
Authors: Wertheim Joel O. , Panneer Nivedha , France Anne Marie , Saduvala Neeraja , Oster Alexandra M.
Published: April 2020

Objective:

To identify correlates of incident HIV infection in rapidly growing HIV molecular clusters.

Design:

Phylogenetic analysis of HIV public health surveillance data.

Methods:

High-priority HIV genetic transmission clusters with evidence of rapid growth in 2012 (i.e. clusters with a pairwise genetic distance ≤0.005 substitutions/site and at least three cases diagnosed in 2012) were identified using HIV-TRACE. Then, we investigated cluster growth, defined as HIV cases diagnosed in the following 5 years that were genetically linked to these clusters. For clusters that grew during the follow-up period, Bayesian molecular clock phylogenetic inference was performed to identify clusters with evidence of incident HIV infection (as opposed to diagnosis of previously infected cases) during this follow-up period.

Results:

Of the 116 rapidly growing clusters identified, 73 (63%) had phylogenetic evidence for an incident HIV case during the 5-year follow-up period. Correlates of an incident HIV case arising in clusters included a greater number of diagnosed but virally unsuppressed cases in 2012, a greater number of inferred undiagnosed cases in the cluster in 2012, and a younger time of most recent common ancestor for the cluster.

Conclusion:

These findings suggest that incident infections in rapidly growing clusters originate equally from diagnosed but unsuppressed cases and undiagnosed infections. These results highlight the importance of promoting retention in care and viral suppression as well as partner notification and other case-finding activities when investigating and intervening on high-priority molecular transmission clusters.
Effectiveness of dolutegravir-based antiretroviral therapy in a real-world setting in a Belgian cohort of 4101 HIV patients
Authors: Nasreddine Rakan , Florence Eric , Vandercam Bernard , Moutschen Michel , Goffard Jean-Christophe , De Munter Paul , Delforge Marc , Marinus Wouter , De Wit Stéphane
Published: April 2020

Objective:

To describe the treatment outcomes of patients receiving dolutegravir (DTG) in a ‘real-world setting’ in Belgium.

Design:

Retrospective, observational, multicenter cohort.

Methods:

Inclusion criteria: HIV-1 patients at least 18 years old having received DTG as part of their combined antiretroviral therapy (cART) between 1 April 2014 and 1 December 2017. Primary endpoint: rate of virologic suppression, defined as plasma HIV-1 viral load less than 50 copies/ml, at weeks 24, 48, and 96. Secondary endpoints: durability, expressed as probability of experiencing loss of virologic suppression by week 96 (defined as two consecutive HIV-1 viral load measurements of at least 200 copies/ml after having initially achieved virologic suppression); immunological response at weeks 24, 48, and 96; incidence of and reasons for DTG discontinuation; and change in weight at week 96.

Results:

Four thousand, one hundred and one patients were included. Through 96 weeks, virologic suppression rate was 96% (on-treatment analysis), probability of experiencing loss of virologic suppression was 7%, and mean increase in CD4+ cell count was 100 cells/μl (SD 220). There were 785 (19.1%) discontinuations of DTG (8.9 discontinuations per 100 patient-years). The most common cause of discontinuation was an adverse drug reaction (ADR; 9.5%) with neuropsychiatric toxicity being the most prevalent (5.2%; 2.4 discontinuations per 100 patient-years). By week 96, the median change in weight for the study population was +2.0 kg (IQR −1 to 5).

Conclusion:

In this large cohort, DTG showed excellent virologic efficacy and was generally well tolerated. Whether DTG results in undesirable weight gain or rather statistically significant results, remains a debate.
Monocyte and CD4+ T-cell antiviral and innate responses associated with HIV-1 inflammation and cognitive impairment
Authors: Sharma Vishakha , Bryant Christopher , Montero Maria , Creegan Matthew , Slike Bonnie , Krebs Shelly J. , Ratto-Kim Silvia , Valcour Victor , Sithinamsuwan Pasiri , Chalermchai Thep , Eller Michael A. , Bolton Diane L.
Published: April 2020

Objective:

Mechanisms underlying immune activation and HIV-associated neurocognitive disorders (HAND) in untreated chronic infection remain unclear. The objective of this study was to identify phenotypic and transcriptional changes in blood monocytes and CD4+ T cells in HIV-1-infected and uninfected individuals and elucidate processes associated with neurocognitive impairment.

Design:

A group of chronically HIV-1-infected Thai individuals (n = 19) were selected for comparison with healthy donor controls (n = 10). Infected participants were further classified as cognitively normal (n = 10) or with HAND (n = 9). Peripheral monocytes and CD4+ T cells were phenotyped by flow cytometry and simultaneously isolated for multiplex qPCR-targeted gene expression profiling directly ex vivo. The frequency of HIV-1 RNA-positive cells was estimated by limiting dilution cell sorting.

Results:

Expression of genes and proteins involved in cellular activation and proinflammatory immune responses was increased in monocytes and CD4+ T cells from HIV-1-infected relative to uninfected individuals. Gene expression profiles of both CD4+ T cells and monocytes correlated with soluble markers of inflammation in the periphery (P < 0.05). By contrast, only modest differences in gene programs were observed between cognitively normal and HAND cases. These included increased monocyte surface CD169 protein expression relative to cognitively normal (P = 0.10), decreased surface CD163 expression relative to uninfected (P = 0.02) and cognitively normal (P = 0.06), and downregulation of EMR2 (P = 0.04) and STAT1 (P = 0.02) relative to cognitively normal.

Conclusion:

Our data support a model of highly activated monocytes and CD4+ T cells associated with inflammation in chronic HIV-1 infection, but impaired monocyte anti-inflammatory responses in HAND compared with cognitively normal.
Genetically-edited induced pluripotent stem cells derived from HIV-1-infected patients on therapy can give rise to immune cells resistant to HIV-1 infection
Authors: Teque Fernando , Ye Lin , Xie Fei , Wang Jiaming , Morvan Maelig G. , Kan Yuet Wai , Levy Jay A.
Published: April 2020

Objective:

To assess the in-vitro CCR5---tropic and CXCR4---tropic HIV---1 infectivity of immune cells, particularly macrophages, derived from CCR5 gene---edited induced pluripotent stem cells (iPSCs) obtained from the peripheral blood mononuclear cells (PBMC) of HIV---infected patients on antiretroviral therapy (ART).

Design:

PBMC were obtained from six patients who had been HIV---infected for over 20 years and were on ART for 1---12 years prior to this study.

Methods:

The PBMC were derived into iPSCs and genetically edited with TALENs or CRISPR---cas9 endonucleases combined with PiggyBac technology to introduce the naturally occurring 32---bp deletion to the CCR5 gene. These iPSCs were differentiated into macrophages, and subsequently challenged with CCR5---tropic or CCR5/CXCR4 dual--- tropic HIV---1 strains. iPSC derivation, gene editing and immune cell differentiation were done in feeder---free, xeno---free in-vitro conditions.

Results:

Multiple unedited (wild---type) and CCR5 gene---edited (mutant) iPSCs were derived from patients’ PBMC. When differentiated into immune cells and HIV---1 challenged, mutant iPSC lines were resistant to CCR5---tropic and to some extent to CCR5/CXCR4 dual---tropic HIV---1 infection when compared to wild---type iPSC lines.

Conclusion:

Our study demonstrates that iPSC---derived, gene---edited immune cells are resistant to distinct HIV---1 strains. These findings have important implications for both in-vitro stem cell development and therapeutic approaches to cure HIV infection.
Application of Transparent Cap-assisted Choledochoscopy in Endoscopic Gallbladder-preserving Surgery
Authors: Jian Wei , Song Yan-zhou , Xiang Qing-feng , Tian Heng-yu , Xie Zhuo-zhao , Yang Jun-bo , Zhang Yi-ming , Zhang Rui-kun , Liu Jia-lin
Published: April 2020

Background:

The gold standard treatment for cholecystolithiasis is laparoscopic cholecystectomy. However, the complications of cholecystectomy have led to adoption of gallbladder-preserving surgery. The study was to investigate significance of transparent cap-assisted choledochoscopy in gallbladder-preserving surgery.

Materials and Methods:

This is a retrospective study of patients who underwent gallbladder-preserving surgery by laparoscopic choledochoscopy along with choledochoscopy with or without a transparent cap from January 2018 to September 2018 in our hospital. The differences in the duration of gallbladder exploration, surgical complications, adverse events, and the recurrence of stones within 6 months after surgery were compared between 2 groups.

Results:

Fifty patients underwent laparoscopic choledochoscopy along with choledochoscopy without transparent cap (Group A), while 50 patients underwent laparoscopic along with transparent cap-assisted choledochoscopy (Group B). Gallbladder exploration time was 27.96±12.24 minutes in Group A, and 12.04±6.01 minutes in Group B. One case had stone recurrence within 6 months in Group B, while 8 cases had stone recurrence in group A.

Conclusions:

Comparing with laparoscope combined with choledochoscopy, transparent cap-assisted choledochoscopy has advantages in gallbladder-preserving surgery.
Prehospital definitive airway is not associated with improved survival in trauma patients
Authors: Tsur Avishai M. , Nadler Roy , Tsur Nir , Sorkin Alex , Bader Tarif , Benov Avi , Glassberg Elon , Chen Jacob
Published: April 2020

BACKGROUND

The American College of Surgeons and the National Association of Emergency Medical Technicians advise securing a definitive airway if there is any doubt about the trauma patient's ability to maintain airway integrity. The objective of this study was to investigate the association between a success in securing a definitive airway in the prehospital setting and survival among trauma patients, in which the provider deemed a definitive airway was necessary.

METHODS

The study included all trauma patients recorded in the Israel Defense Forces Trauma Registry between the years 2006 and 2018 for whom a prehospital attempt of securing a definitive airway was documented. The successful definitive airway group was defined by explicit documentation of success in either endotracheal intubation or cricothyrotomy. Logistic regression was performed to determine the association between success in securing a definitive airway and survival.

RESULTS

A total of 566 (3.6%) trauma patients underwent attempts to secure a definitive airway (successful in 425 patients and unsuccessful in 141). Prehospital survival rates were similar (77.6% vs. 78.0%, p = 0.928) between the groups. Whether the definitive airway was successful did not affect the rates of prehospital survival, neither before (odds ratio, 0.98; 95% confidence interval, 0.61–1.54) nor after adjustment for the other factors (odds ratio, 0.91; 95% confidence interval, 0.55–1.46).

CONCLUSION

This study was unable to find an association between a successful definitive airway in the prehospital setting and survival, even after adjustment for injury characteristics and in multiple models. Furthermore, survival rates were high among trauma patients in which the provider deemed a definitive airway as necessary yet failed in securing one. These results suggest that the liberal use of these invasive airway procedures in the prehospital setting should be reconsidered.

LEVEL OF EVIDENCE

Retrospective study, lebel III.
Blood product needs and transfusion timelines for the multisite massive Paris 2015 terrorist attack: A retrospective analysis
Authors: Martinez Thibault , François Anne , Pouget Thomas , Carli Pierre , Lapostolle Frédéric , Gauss Tobias , Hamada Sophie Rym , Langlois Matthieu , Yordanov Youri , Féral-Pierssens Anne-Laure , Woloch Alexandre , Ogereau Carl , Gayat Etienne , Attias Arié , Pateron Dominique , Castier Yves , Ludes Bertrand , Dolla Emmanuelle , Tourtier Jean-Pierre , Riou Bruno , Raux Mathieu , Ausset Sylvain ,   TRAUMABASE group
Published: April 2020

OBJECTIVE

Hemorrhage is the leading cause of death after terrorist attack, and the immediacy of labile blood product (LBP) administration has a decisive impact on patients' outcome. The main objective of this study was to evaluate the transfusion patterns of the Paris terrorist attack victims, November 13, 2015.

METHODS

We performed a retrospective analysis including all casualties admitted to hospital, aiming to describe the transfusion patterns from admission to the first week after the attack.

RESULTS

Sixty-eight of 337 admitted patients were transfused. More than three quarters of blood products were consumed in the initial phase (until November 14, 11:59 pm), where 282 packed red blood cell (pRBC) units were transfused along with 201 plasma and 25 platelet units, to 55 patients (16% of casualties). Almost 40% of these LBPs (134 pRBC, 73 plasma, 8 platelet units) were transfused within the first 6 hours after the attack. These early transfusions were massive transfusion (MT) for 20 (6%) of 337 patients, and the average plasma/red blood cell ratio was 0.8 for MT patients who received 366 (72%) of 508 LBPs.

The median time from admission to pRBC transfusion was 57 (25–108) minutes and 208 (52–430) minutes for MT and non-MT patients, respectively. These same time intervals were 119 (66–202) minutes and 222 (87–381) minutes for plasma and 225 (131–289) minutes and 198 (167–230) minutes for platelets.

CONCLUSION

Our data suggest that improving transfusion procedures in mass casualty setting should rely more on shortening the time to bring LBP to the bedside than in increasing the stockpile.

LEVEL OF EVIDENCE

Epidemiological study, Therapeutic IV.
Establishing an enduring Military Trauma Mortality Review: Misconceptions and lessons learned
Authors: Janak Jud C. , Mazuchowski Edward L. , Kotwal Russ S. , Howard Jeffrey T. , Stockinger Zsolt T. , Gurney Jennifer M. , Shackelford Stacy A.
Published: April 2020

Under direction from the Defense Health Agency, subject matter experts (SMEs) from the Joint Trauma System, Armed Forces Medical Examiner System, and civilian sector established the Military Trauma Mortality Review process. To establish the most empirically robust process, these SMEs used both qualitative and quantitative methods published in a series of peer-reviewed articles over the last 3 years. Most recently, the Military Mortality Review process was implemented for the first time on all battle-injured service members attached to the United States Special Operations Command from 2001 to 2018. The current Military Mortality Review process builds on the strengths and limitations of important previous work from both the military and civilian sector. To prospectively improve the trauma care system and drive preventable death to the lowest level possible, we present the main misconceptions and lessons learned from our 3-year effort to establish a reliable and sustainable Military Trauma Mortality Review process. These lessons include the following: (1) requirement to use standardized and appropriate lexicon, definitions, and criteria; (2) requirement to use a combination of objective injury scoring systems, forensic information, and thorough SME case review to make injury survivability and death preventability determinations; (3) requirement to use nonmedical information to make reliable death preventability determinations and a comprehensive list of opportunities for improvement to reduce preventable deaths within the trauma care system; and (4) acknowledgment that the military health system still has gaps in current infrastructure that must be addressed to globally and continuously implement the process outlined in the Military Trauma Mortality Review process in the future.

LEVEL OF EVIDENCE

Level III.
Evaluating and improving current risk prediction tools in emergency laparotomy
Authors: Barazanchi Ahmed , Bhat Sameer , Palmer-Neels Kate , Macfater Wiremu S. , Xia Weisi , Zeng Irene , Taneja Ashish , MacCormick Andrew D. , Hill Andrew G.
Published: April 2020

PURPOSE

Emergency laparotomy (EL) encompasses a high-risk group of operations, which are increasingly performed on a heterogeneous population of patients, making preoperative risk assessment potentially difficult. The UK National Emergency Laparotomy Audit (NELA) recently produced a risk predictive tool for EL that has not yet been externally validated. We aimed to externally validate and potentially improve the NELA tool for mortality prediction after EL.

METHODOLOGY

We reviewed computer and paper records of EL patients from May 2012 to June 2017 at Middlemore Hospital (New Zealand). The inclusion criteria mirrored the UK NELA. We examined the NELA, Portsmouth Physiological and Operative Severity Score for the enUmeration of Mortality (P-POSSUM), Acute Physiology and Chronic Health Evaluation II (APACHE-II), and American College of Surgeons National Surgical Quality Improvement Programs risk predictive tools for 30-day mortality. The Hosmer-Lemeshow test was used to assess calibration, and the c statistic, to evaluate discrimination (accuracy) of the tools. We added the modified frailty index (mFI) and nutrition to improve the accuracy of risk predictive tools.

RESULTS

A total of 758 patients met the inclusion criteria, with an observed 30-day mortality of 7.9%. The NELA was the only well calibrated tool, with predicted 30-day mortality of 7.4% (p = 0.22). When combined with mFI and nutritional status, the c statistic for NELA improved from 0.83 to 0.88. American College of Surgeons National Surgical Quality Improvement Programs, APACHE-II, and P-POSSUM had lower c statistics, albeit also showing an improvement (0.84, 0.81, and 0.74, respectively).

CONCLUSION

We have demonstrated the NELA tool to be most predictive of mortality after EL. The NELA tool would therefore facilitate preoperative risk assessment and operative decision making most precisely in EL. Future research should consider adding mFI and nutritional status to the NELA tool.

LEVEL OF EVIDENCE

Level IV; Retrospective observational cohort study.