bluuebunny/crossref_metadata_2025 huggingface dataset:
DEG 15, an update of the Database of Essential Genes that includes built-in analysis tools
Authors: Luo Hao , Lin Yan , Liu Tao , Lai Fei-Liao , Zhang Chun-Ting , Gao Feng , Zhang Ren
Published: October 2020

Essential genes refer to genes that are required by an organism to survive under specific conditions. Studies of the minimal-gene-set for bacteria have elucidated fundamental cellular processes that sustain life. The past five years have seen a significant progress in identifying human essential genes, primarily due to the successful use of CRISPR/Cas9 in various types of human cells. DEG 15, a new release of the Database of Essential Genes (www.essentialgene.org), has provided major advancements, compared to DEG 10. Specifically, the number of eukaryotic essential genes has increased by more than fourfold, and that of prokaryotic ones has more than doubled. Of note, the human essential-gene number has increased by more than tenfold. Moreover, we have developed built-in analysis modules by which users can perform various analyses, such as essential-gene distributions between bacterial leading and lagging strands, sub-cellular localization distribution, enrichment analysis of gene ontology and KEGG pathways, and generation of Venn diagrams to compare and contrast gene sets between experiments. Additionally, the database offers customizable BLAST tools for performing species- and experiment-specific BLAST searches. Therefore, DEG comprehensively harbors updated human-curated essential-gene records among prokaryotes and eukaryotes with built-in tools to enhance essential-gene analysis.
Search for Viral Infections in Cerebrospinal Fluid From Patients With Autoimmune Encephalitis
Authors: Perlejewski Karol , Pawełczyk Agnieszka , Bukowska-Ośko Iwona , Rydzanicz Małgorzata , Dzieciątkowski Tomasz , Paciorek Marcin , Makowiecki Michał , Caraballo Cortés Kamila , Grochowska Marta , Radkowski Marek , Laskus Tomasz
Published: October 2020

Background

It has been reported that virus-mediated brain tissue damage can lead to autoimmune encephalitis (AE) characterized by the presence of antibodies against neuronal surface antigens. In the study, we investigate the presence of viruses in cerebrospinal fluid (CSF) from patients with AE using reverse transcription polymerase chain reaction (RT-PCR)/PCR and shotgun metagenomics.

Methods

CSF samples collected from 200 patients with encephalitis were tested for the presence of antibodies against antiglutamate receptor (NMDAR), contactin-associated protein 2 (CASPR2), glutamate receptors (type AMPA1/2), leucine-rich glioma-inactivated protein 1 (LGI1), dipeptidyl aminopeptidase-like protein 6 (DPPX), and GABA B receptor, and those found positive were further analyzed with real-time RT-PCR/PCR for common viral neuroinfections and shotgun DNA- and RNA-based metagenomics.

Results

Autoantibodies against neuronal cells were detected in CSF from 8 individuals (4% of all encephalitis patients): 7 (3.5%) had anti-NMDAR and 1 (0.5%) had anti-GABA B. RT-PCR/PCR identified human herpes virus type 1 (HSV-1; 300 copies/mL) and the representative of Enterovirus genus (550 copies/mL) in 1 patient each. Torque teno virus (TTV) was found in another patient using metagenomic analysis, and its presence was confirmed by specific PCR.

Conclusions

We detected the presence of HSV, TTV, and Enterovirus genus in CSF samples from 3 out of 8 AE patients. These findings support the concept of viral involvement in the pathogenesis of this disease.
Toward 2D materials for flexible electronics: opportunities and outlook
Authors: Glavin Nicholas R , Muratore Christopher , Snure Michael
Published: October 2020

Two-dimensional nanomaterials exhibit exceptional multifunctional properties including high-electron mobilities/saturation velocities, high surface to volume ratios, unique layered structures and mechanical compliance, positioning the class of materials to be influential in next-generation flexible electronics for applications in wearables and the Internet of things. In this perspective, three key areas of interest are identified that take advantage of the multifunctional nature of these materials including molecular sensing, van der Waals transfer and compliant radio frequency electronics. Significantly more progress needs to be made to realize commercialization of these materials, but the revolutionary accessible properties may reveal themselves in these three key areas of future flexible electronic systems.
4U 1608–52 as a quasi-persistent X-ray source
Authors: Šimon Vojtěch
Published: October 2020

4U 1608–52 is a soft X-ray transient. The analysis presented here of a particular part of its X-ray activity uses observations of RXTE/ASM and Swift/BAT. We show a time segment (MJD 54262–MJD 55090) (828 d) in which 4U 1608–52 behaved as a quasi-persistent X-ray source with a series of bumps, with a complicated relation between the evolution of fluxes in the soft (1.5–12 keV) and the hard (15–50 keV) X-ray regions. We ascribe these bumps to a series of propagations of heating and cooling fronts over the inner disk region without any transitions to the true quiescence. 4U 1608–52 oscillated around the boundary between the dominance of the Comptonized component and the dominance of the multicolor accretion disk in its luminosity. Only some of the bumps in this series were accompanied by a transition from the hard to the soft state; if it occurred, it displayed a strong hysteresis effect. The hard-band emission with the dominant Comptonized component was present for most of this active state and showed a cycle of about 40 d. We argue that the cyclic variations of flux come from the inner disk region, not, e.g., from a jet. We also discuss the observed behavior of 4U 1608–52 in the context of other quasi-persistent low-mass X-ray binaries.
A simple index predicting mortality in acutely hospitalized patients
Authors: Froom P , Shimoni Z , Benbassat J , Silke B
Published: October 2020

Background

Mortality rates used to evaluate and improve the quality of hospital care are adjusted for comorbidity and disease severity. Comorbidity, measured by International Classification of Diseases codes, do not reflect the severity of the medical condition, that requires clinical assessments not available in electronic databases, and/or laboratory data with clinically relevant ranges to permit extrapolation from one setting to the next.

Aim

To propose a simple index predicting mortality in acutely hospitalized patients.

Design

Retrospective cohort study with internal and external validation.

Methods

The study populations were all acutely admitted patients in 2015–16, and in January 2019–November 2019 to internal medicine, cardiology and intensive care departments at the Laniado Hospital in Israel, and in 2002–19, at St. James Hospital, Ireland. Predictor variables were age and admission laboratory tests. The outcome variable was in-hospital mortality. Using logistic regression of the data in the 2015–16 Israeli cohort, we derived an index that included age groups and significant laboratory data.

Results

In the Israeli 2015–16 cohort, the index predicted mortality rates from 0.2% to 32.0% with a c-statistic (area under the receiver operator characteristic curve) of 0.86. In the Israeli 2019 validation cohort, the index predicted mortality rates from 0.3% to 38.9% with a c-statistic of 0.87. An abbreviated index performed similarly in the Irish 2002–19 cohort.

Conclusions

Hospital mortality can be predicted by age and selected admission laboratory data without acquiring information from the patient’s medical records. This permits an inexpensive comparison of performance of hospital departments.
Signalling to Experts
Authors: Kurlat Pablo , Scheuer Florian
Published: October 2020

We study competitive equilibria in a signalling economy with heterogeneously informed buyers. In terms of the classic Spence (1973, The Quarterly Journal of Economics, 87, 355—374) model of job market signalling, firms have access to direct but imperfect information about worker types, in addition to observing their education. Firms can be ranked according to the quality of their information, i.e., their expertise. In equilibrium, some high-type workers forgo signalling and are hired by better informed firms, which make positive profits. Workers’ education decisions and firms’ use of their expertise are strategic complements, allowing for multiple equilibria that can be Pareto ranked. We characterize wage dispersion and the extent of signalling as a function of the distribution of expertise among firms. Our model can also be applied to a variety of other signalling problems, including securitization, corporate financial structure, insurance markets, or dividend policy.
Shedding Light on Drug-Induced Liver Injury: Activation of T Cells From Drug Naive Human Donors With Tolvaptan and a Hydroxybutyric Acid Metabolite
Authors: Hammond Sean , Gibson Andrew , Jaruthamsophon Kanoot , Roth Sharin , Mosedale Merrie , Naisbitt Dean J
Published: October 2020

Exposure to tolvaptan is associated with a significant risk of liver injury in a small fraction of patients with autosomal dominant polycystic kidney disease. The observed delayed onset of liver injury of between 3 and 18 months after commencing tolvaptan treatment, along with rapid recurrence of symptoms following re-challenge is indicative of an adaptive immune attack. This study set out to assess the intrinsic immunogenicity of tolvaptan and pathways of drug-specific T-cell activation using in vitro cell culture platforms. Tolvaptan (n = 7), as well as oxybutyric (DM-4103, n = 1) and hydroxybutyric acid (DM-4107, n = 18) metabolite-specific T-cell clones were generated from tolvaptan naive healthy donor peripheral blood mononuclear cells. Tolvaptan and DM-4103 T-cell clones could also be activated with DM-4107, whereas T-cell clones originally primed with DM-4107 were highly specific to this compound. A signature cytokine profile (IFN-γ, IL-13, granzyme B, and perforin) for almost all T-cell clones was identified. Mechanistically, compound-specific T-cell clone activation was dependent on the presence of soluble drug and could occur within 4 h of drug exposure, ruling out a classical hapten mechanism. However, antigen processing dependence drug presentation was indicated in many T-cell clones. Collectively these data show that tolvaptan-associated liver injury may be attributable to an adaptive immune attack upon the liver, with tolvaptan- and metabolite-specific T cells identified as candidate effector cells in such etiology.
Nulla Per Os (NPO) guidelines: time to revisit?
Authors: Friedrich Sabine , Meybohm Patrick , Kranke Peter
Published: October 2020

Purpose of review

Preoperative fasting guidelines are generalized to elective procedures and usually do not distinguish between the ambulatory and inpatient setting. Prevalence of aspiration is low while prolonged preoperative fasting is common clinical reality. Recently, changes in preoperative fasting guidelines have been widely discussed.

Recent findings

Rates of prolonged clear fluid fasting (>4 h) prior to surgery are reported in up to 80% of patients with mean fasting duration of up to 16 h and beyond. Prolonged fasting may result in adverse effects such as intraoperative hemodynamic instability, postoperative delirium, patient discomfort, and extended hospital length of stay. Liberal approaches allowing clear fluids up to 1 h prior to anesthesia or until premedication/call to the operating room have shown no increase in adverse events among children. Various anesthesia societies now encourage clear fluid intake up to 1 h prior to pediatric elective anesthesia. Similar reports in the adult cohort are scarce.

Allowing sips of water until call to the operating room may help reducing prolonged preoperative fasting and improving patient comfort while keeping a flexibility in operating room schedule. The feasibility and safety of a liberal clear fluid fasting regimen among adults undergoing elective anesthesia needs to be evaluated in future studies.
Suture Stabilization of Open Physeal Fractures of the Great Toe Distal Phalanx (Seymour Fracture)
Authors: Reid Daniel B.C. , Deckey David G. , Procaccini Michaela , Eberson Craig P.
Published: October 2020

Background:

Open physeal fractures of the distal phalanx of the hallux are analogous to Seymour fractures of the hand. When missed, these injuries can result in long-term sequelae including infection, pain, nail deformity, and physeal arrest. Nevertheless, there is a paucity in the literature regarding optimal surgical treatment for these challenging injuries. We present a novel technique and case series for suture-only stabilization of Seymour fractures of the great toe.

Methods:

Billing records were used to identify all children aged 18 years or younger who underwent operative treatment open distal phalanx fracture of the hallux with an associated nail bed injury. Electronic medical records and plain imaging were reviewed to identify mechanism of injury, surgical technique, results, complications, and follow-up.

Results:

Five boys with a mean age of 10.3 years (range, 5 to 13 y) met inclusion criteria. Forty percent (2/5) of injuries were missed by the initial treating providers. Only 2 patients presented to our institution primarily; 60% (3/5) patients were transferred from other facilities. The mechanism of injury was variable but generally involved “stubbing” the toe. The mean time from injury to surgical treatment was 2.6 days (range, 0 to 6 d). Median follow-up was 2 months (range, 1 to 96 mo). No patient complications (including infection) or reoperations were reported. On follow-up imaging, no physeal bars were evident on patients treated with suture-only technique.

Conclusions:

Seymour fracture of the hallux are uncommon, and there is frequently a delay in both presentation and diagnosis. Providers should have increased suspicion for these injuries when a physeal fracture of the great toe is associated with bleeding or nail bed injury. Currently, no consensus exists for treatment of these injuries. Suture-only stabilization represents a simple, reliable alternative to pin fixation.

Level of Evidence:

Level IV—retrospective case series.
Safe Spine Surgery During the COVID-19 Pandemic
Authors: Toombs Courtney S. , Boody Barrett S. , Bronson Wesley H. , Girasole Gerard J. , Russo Glenn S.
Published: October 2020

Safe spine surgery is possible during the COVID-19 pandemic. Certain urgent procedures must still be performed during this challenging time to prevent permanent long-term disability or death for patients. Precautions must be taken in the operating room to optimize safety, including the use of personal protective equipment and appropriate room setup and anesthesia and equipment optimization. Evidence-based guidelines to create a safe operative paradigm for use in future viral outbreaks are paramount.
Extracorporeal Membrane Oxygenation in Severe Acute Respiratory Distress Syndrome: Possible Late Indication for Coronavirus Disease 2019?
Authors: Soumagne Thibaud , Grillet Franck , Piton Gaël , Winiszewski Hadrien , Capellier Gilles
Published: October 2020

Background:

There is now substantial evidence to support venovenous extracorporeal membrane oxygenation efficacy and safety for patients with severe acute respiratory distress syndrome. However, recent guidelines recommend against the initiation of extracorporeal membrane oxygenation in patients with mechanical ventilation for coronavirus disease 2019 severe acute respiratory distress syndrome for greater than 7–10 days.

Case Summary:

We report the case of a patient with coronavirus disease 2019 severe acute respiratory distress syndrome with successful late venovenous extracorporeal membrane oxygenation initiation after 20 days of mechanical ventilation. Respiratory compliance, arterial blood gases, and radiological lesions improved progressively under venovenous extracorporeal membrane oxygenation and ultraprotective ventilation. The patient was discharged from ICU.

Conclusions:

As coronavirus disease 2019 is a new and incompletely understood entity, we believe that late extracorporeal membrane oxygenation may be considered in selected patients as a bridge to recovery. Further prospective studies are, however, needed.
In-House, Overnight Physician Staffing: A Cross-Sectional Survey of Canadian Adult ICUs
Authors: Maratta Christina , Hutchison Kristen , Moore Gregory P. , Bagshaw Sean M. , Granton John , Kirpalani Haresh , Stelfox Henry Thomas , Ferguson Niall , Cook Deborah , Parshuram Christopher S.
Published: October 2020

Objectives:

Overnight physician staffing in the ICU has been recommended by the Society of Critical Care Medicine and the Leapfrog Consortium. We conducted a survey to review practice in the current era and to compare this with results from a 2006 survey.

Design:

Cross-sectional survey.

Setting:

Canadian adult ICUs.

Participants:

ICU directors.

Interventions:

None.

Measurement and Main Results:

A 29-question survey was sent to ICU directors describing overnight staffing by residents, fellows, nurse practitioners, and staff physicians, as well as duty duration, clinical responsibilities, and unit characteristics. We established contact with 122 ICU directors, of whom 107 (88%) responded. Of the 107 units, 60 (56%) had overnight in-house physicians. Compared with ICUs without overnight in-house physician coverage, ICUs with in-house physicians were in larger hospitals (p < 0.0001), had more beds (p < 0.0001), had more ventilated patients (p < 0.0001), and had more admissions (p < 0.0001). Overnight in-house physicians were first year residents (R1) in 20 of 60 (33%), second to fifth year residents (R2–R5) in 46 of 60 (77%), and Critical Care Medicine trainees in 19 of 60 (32%). Advanced practice nurses provided overnight coverage in four of 107 ICUs (4%). The most senior in-house physician was a staff physician in 12 of 60 ICUs (20%), a Critical Care Medicine trainee in 14 of 60 (23%), and a resident (R2–R5) in 20 of 60 (33%). The duration of overnight duty was on average 20–24 hours in 22 of 46 units (48%) with R2–R5 residents and 14 of 19 units (74%) covered by Critical Care Medicine trainees.

Conclusions:

Variability of in-house overnight physician presence in Canadian adult ICUs is linked to therapeutic complexity and unit characteristics and has not changed significantly over the decade since our 2006 survey. Additional evidence about patient and resident outcomes would better inform decisions to revise physician scheduling in Canadian ICUs.
Key Role of Respiratory Quotient to Reduce the Occurrence of Hypoxemia During Extracorporeal Gas Exchange: A Theoretical Analysis*
Authors: Cipriani Elisa , Langer Thomas , Bottino Nicola , Brusatori Serena , Carlesso Eleonora , Colombo Sebastiano Maria , Zanella Alberto , Pesenti Antonio , Grasselli Giacomo
Published: October 2020

Objectives:

Extracorporeal respiratory support, including low blood flow systems providing mainly extracorporeal CO2 removal, are increasingly applied in clinical practice. Gas exchange physiology during extracorporeal respiratory support is complex and differs between full extracorporeal membrane oxygenation and extracorporeal CO2 removal. Aim of the present article is to review pathophysiological aspects which are relevant for the understanding of hypoxemia development during extracorporeal CO2 removal. We will describe the mathematical and physiologic background underlying changes in respiratory quotient and alveolar oxygen tension during venovenous extracorporeal gas exchange and highlight the clinical implications.

Design:

Theoretical analysis of venovenous extracorporeal gas exchange.

Setting:

Italian university research hospital.

Patients:

None.

Interventions:

None.

Measurements and Main Results:

While the effect of extracorporeal CO2 removal on the respiratory quotient of the native lung has long been known, the role of extracorporeal oxygenation in dictating changes in the respiratory quotient has been less addressed. Indeed, both extracorporeal CO2 removal and extracorporeal oxygen delivery affect the respiratory quotient of the native lung and thus influence the alveolar Po
2. Indeed, for the same amount of extracorporeal CO2 extraction, it is possible to reduce the Fio
2, reduce the risk of absorption atelectasis, and maintain the same alveolar Po
2, by increasing the extracorporeal oxygen delivery.

Conclusions:

Worsening of hypoxemia is frequent during low-flow extracorporeal CO2 removal combined with ultraprotective mechanical ventilation. In this context, increasing extracorporeal oxygen delivery, increases the respiratory quotient of the native lung and could reduce both the occurrence of alveolar hypoxia and absorption atelectasis, thus optimizing the residual lung function.
Association Between Pediatric Delirium and Quality of Life After Discharge*
Authors: Silver Gabrielle , Doyle Hannah , Hegel Emily , Kaur Savneet , Mauer Elizabeth A. , Gerber Linda M. , Traube Chani
Published: October 2020

Objective:

Delirium occurs frequently in critically ill children, with highest rates reported in children under 5 years old. The objective of this study was to measure the residual effect of delirium on quality of life at 1 and 3 months after hospital discharge.

Design:

Prospective observational cohort study.

Setting:

Urban academic PICU.

Patients:

Children younger than five years of age at time of admission to the PICU.

Interventions:

All children were screened for delirium (using the Cornell Assessment for Pediatric Delirium) throughout their stay in the PICU. Quality of life was measured using the Infant-Toddler Quality of Life questionnaire at three time points: baseline, 1 month, and 3 months after hospital discharge. Infant-Toddler Quality of Life scores were compared between children who did and did not develop delirium.

Measurements and Main Results:

Two hundred seven children were enrolled. One hundred twenty-two completed the 1-month follow-up, and 117 completed the 3-month follow-up. Fifty-six children (27%) developed delirium during their PICU stay. At follow-up, Infant-Toddler Quality of Life scores for the PICU cohort overall were consistently lower than age-related norms. When analyzed by delirium status, children who had experienced delirium scored lower in every quality of life domain when compared with children who did not experience delirium. Even after controlling for severity of illness, delirious patients demonstrated an average 11-point lower general health score than nondelirious patients (p = 0.029).

Conclusion:

This pilot study shows an independent association between delirium and decreased quality of life after hospital discharge in young children.
Variations in Criteria for Eligibility Determination for Early Intervention Services with a Focus on Eligibility for Children with Neonatal Complications
Authors: Dempsey Allison G. , Goode Rachel H. , Colon Marcos T. , Holubeck Phil , Nsier Hisham , Zopatti Katherine , Needelman Howard
Published: October 2020

Objective:

The purpose of this policy review is to describe data on eligibility determination practices for early intervention (EI) services across the United States as they particularly relate to eligibility determination for children seen in neonatal follow-up clinics.

Method:

Policy information was gathered from posted information on state EI websites and confirmed through follow-up phone calls. Information collected included definition of delay, approved measures for developmental assessment, and inclusion criteria for medically at-risk status based on birth weight, prematurity, and/or neonatal abstinence syndrome/prenatal exposure.

Results:

States varied widely across enrollment practices and policies. Forty percent of states defined eligibility based on percent delay (vs SD). Thirty-five states had criteria for enrollment based on birth weight and/or prematurity, and 19 states specifically allowed enrollment for an infant with neonatal abstinence syndrome.

Conclusion:

Providers working in neonatal follow-up clinics should be carefully educated about the eligibility criteria and approved tests for assessing development in the states in which they practice, recognizing that there is obvious and significant variability across states.
Factors Associated with Resilience in Families of Children with Autism Spectrum Disorder
Authors: Al-Jadiri Aseel , Tybor David J. , Mulé Christina , Sakai Christina
Published: October 2020

Objectives:

Families of children with autism spectrum disorder (ASD) report high levels of stress and poor psychological functioning. Resilience serves to buffer these challenges. Little is known about the factors associated with resilience in these families.

Methods:

Data from the National Survey of Children's Health (NSCH) 2016 were used to investigate independent child, parent, and health care factors associated with resilience in families of children with ASD. We used the NSCH's family resilience composite derived from 4 survey questions focused on (1) communication, (2) working together to solve problems, (3) drawing on strengths, and (4) staying hopeful during difficult times. We defined family resilience as high or low based on the number of questions answered “all of the time” or “most of the time” versus “some of the time” or “none,” respectively. Using survey weights, univariate and multivariate logistic regression analyses identified associations of child, parent, and health care factors with low family resilience.

Results:

We analyzed data representing 1151 children with ASD. Low resilience was reported in 32% of families. Low family resilience was significantly associated with parent factors such as not having someone to turn to for support, cutting work hours, and feeling “child hard to care for”; child ASD-related factors such as moderate ASD severity; and health care factors such as lack of satisfaction in communications with providers.

Conclusion:

The findings highlight specific vulnerabilities in families of children with ASD that are associated with low family resilience. Intervention approaches that have the ability to improve overall family resilience should be carefully considered.
Healthy Vascular Aging Is Associated With Higher Cardiorespiratory Fitness
Authors: Fleenor Bradley S. , Carlini Nicholas A. , Kaminsky Leonard A. , Whaley Mitchell H. , Peterman James E. , Harber Matthew P.
Published: October 2020

Background:

Healthy vascular aging (HVA) and cardiorespiratory fitness (CRF) are each independently associated with lower cardiovascular disease-related mortality. It is unknown, however, whether the CRF-related reductions in cardiovascular disease risk are related to HVA. We hypothesized that HVA would be associated with higher CRF in men and women from the Ball State Adult Fitness Longitudinal Lifestyle STudy (BALL ST).

Methods:

Apparently healthy men and women ≥50 yr of age from the BALL ST cohort (n = 101) who underwent a maximal cardiopulmonary exercise test to assess CRF (V˙O
2peak) were included in the study. Participants were divided into either HVA, defined as brachial systolic blood pressure <140/90 mm Hg without taking medications and carotid-femoral pulse wave velocity <7.6 m/sec, or no HVA for subjects with SBP >140/90 mm Hg and/or PWV >7.6 m/sec.

Results:

Participants with HVA had a higher age- and sex-adjusted CRF percentile (62 ± 5 vs 47 ± 3, P < .05), with women having a greater prevalence of HVA than men (36% vs 15%, P < .05). Both carotid-femoral pulse wave velocity (r =−0.27, P < .05) and brachial systolic blood pressure (r =−0.23, P < .05) were independently and inversely associated with CRF for the entire cohort. Men and women with HVA were younger having a lower body fat percentage and higher low-density lipoprotein cholesterol (P < .05, all).

Conclusions:

These data demonstrate that HVA is associated with higher CRF, which may partially explain the preventative cardioprotective effects of CRF.
Predictors of Medication Adherence of Patients With Coronary Heart Disease After Percutaneous Coronary Intervention
Authors: He Qing-Hua , Zheng Jing , Liu Jia-Li , Wang Jun , You Li-Ming
Published: October 2020

Background

The theory of planned behavior (TPB), combined with social support, forms the extended TPB, which has shown to predict adherence to health-related behavior effectively, but few studies have applied it to explain medication adherence in patients with coronary heart disease (CHD) after percutaneous coronary intervention (PCI).

Objectives

The aim of this study was to explore the factors associated with medication adherence and the underlying mechanisms based on the extended TPB among patients with CHD after PCI.

Methods

A cross-sectional descriptive study was conducted among patients with CHD after PCI in 2 major hospitals in Guangzhou, China. Medication adherence was measured with the Medication Adherence Report Scale. Constructs of the TPB contributing to medication adherence were assessed by the Theory of Planned Behavior Questionnaire for Medication Adherence. Social support was measured by the Multidimensional Scale of Perceived Social Support. Structural equation modeling was used to examine the hypotheses based on the extended TPB.

Results

A total of 300 patients were surveyed and 26.0% of them were nonadherent. The structural equation modeling had good fit indices and estimated 62.6% of the variance in medication adherence. Regarding the relationships between the extended TPB constructs and medication adherence, “intention” was directly associated with medication adherence, and “perceived behavioral control” positively predicted medication adherence directly and indirectly. “Affective attitude” and “subjective norm” were indirectly associated with medication adherence through “intention.” Social support exerted an indirect effect on medication adherence through “subjective norm.”

Conclusions

The extended TPB is an appropriate model to predict medication adherence and provides an effective framework for adherence-enhancing interventions.
The impact of fungal allergic sensitization on asthma
Authors: Kao Christina C. , Hanania Nicola A. , Parulekar Amit D.
Published: October 2020

Purpose of review

Fungal sensitization may contribute to the development of asthma as well as asthma severity. The purpose of this review is to summarize existing knowledge about the pathophysiology, diagnosis, and management of fungal sensitization in asthma and highlight unmet needs and target areas for future investigation.

Recent findings

Fungal sensitization may occur by a normal or aberrant immune response. Allergic sensitization to fungi is mediated by the adaptive immune response driven by TH2 cells and the innate immune response driven by the innate lymphoid cells group 2. Diagnosis of fungal sensitization can be made by either skin prick testing or measurement of fungal-specific serum IgE. Fungal sensitization in asthma has been associated with worse disease severity, including reduced lung function, increased risk of hospitalizations, and life-threatening asthma. A spectrum of disease related to fungal sensitization has been described in asthma including allergic bronchopulmonary mycosis and severe asthma with fungal sensitization (SAFS). The role of antifungals and targeted biologic therapy in asthma with fungal sensitization need further investigation.

There is increasing awareness of the contribution of fungal sensitization to asthma severity. However, there are no therapies with proven efficacy. Randomized clinical trials are needed to further investigate the role of biologics.
Hypertriglyceridemia: new approaches in management and treatment
Authors: Wolska Anna , Yang Zhi-Hong , Remaley Alan T.
Published: October 2020

Purpose of review

Hypertriglyceridemia (HTG), a form of dyslipidemia characterized by elevated plasma of triglycerides (TG), is associated with an increased risk for acute pancreatitis. Moreover, HTG has recently been shown to be linked to the development of atherosclerotic cardiovascular disease (ASCVD); therefore, there is a great interest in better understanding the pathophysiology of HTG and improving its clinical management. In this review, we briefly describe TG metabolism, recent guidelines for the clinical management of HTG and provide an overview of the current and potential new therapies for HTG.

Recent findings

Screening patients for HTG is valuable for not only identifying patients with extreme TG elevations, who are at risk for pancreatitis, but also for managing ASCVD risk in patients with more moderate forms of HTG. Therefore, the most recent USA guidelines for cardiovascular diseases recommend using TG as a risk enhancer test, leading to a more aggressive treatment of patients with intermediate risk. Currently, there are several available approaches for reducing plasma TG, which include lifestyle changes, fibrates and omega-3 fatty acid treatment. The addition of eicosapentaenoic acid (EPA) on top of statins has recently been shown to significantly reduce ASCVD events. Nevertheless, there is an unmet need for more effective treatment options. Several new therapies based on newly identified targets in TG metabolism, such as apolipoprotein C-III and angiopoietin-like 3 protein, are currently under development.

The clinical management of HTG is important in the prevention and treatment of acute pancreatitis and also impacts on how ASCVD risk is managed. More work needs to be done to establish the mechanism for the ability of how EPA lowers ASCVD and how to best integrate it with other lipid-lowering therapies. The efficacy and safety of the novel therapies for HTG should be established soon in the ongoing late-stage clinical trials.
Targeting epigenetics as atherosclerosis treatment: an updated view
Authors: Neele Annette E. , Willemsen Lisa , Chen Hung-Jen , Dzobo Kim E. , de Winther Menno P.J.
Published: October 2020

Purpose of review

This review discusses the current developments on epigenetic inhibition as treatment for atherosclerosis.

Recent findings

The first phase III clinical trial targeting epigenetics in cardiovascular disease (CVD), BETonMACE, using the bromodomain inhibitor apabetalone (RVX-208) showed no significant effect on major adverse cardiovascular events (MACE) in patients with type II diabetes, low HDL-c and a recent acute coronary artery event compared with its placebo arm.

Preclinical and clinical studies suggest that targeting epigenetics in atherosclerosis is a promising novel therapeutic strategy against CVD. Interfering with histone acetylation by targeting histone deacetylates (HDACs) and bromodomain and extraterminal domain (BET) proteins demonstrated encouraging results in modulating disease progression in model systems. Although the first phase III clinical trial targeting BET in CVD showed no effect on MACE, we suggest that there is sufficient potential for future clinical usage based on the outcomes in specific subgroups and the fact that the study was slightly underpowered. Lastly, we propose that there is future window for targeting repressive histone modifications in atherosclerosis.
The fish-oil paradox
Authors: Nicholls Stephen J. , Nelson Adam J.
Published: October 2020

Purpose of review

Increasing interest has focused on the potential cardioprotective effects of the omega-3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) on the basis of findings from epidemiology and cohort studies. This review will summarize the findings of contemporary clinical trials of omega-3 fatty acids.

Recent findings

Although a large clinical trial performed prior to the widespread use of statins demonstrated cardiovascular benefit with fish oils, subsequent studies have failed to reproduce this result. More recent studies have demonstrated a reduction in cardiovascular risk with administration of high-dose EPA, but not a carboxylic acid formulation containing both EPA and DHA or with lower doses of omega-3 fatty acids.

Administration of omega-3 fatty acids differing in either composition or dose produce variable effects on cardiovascular outcomes. This has implications for both the public health and pharmacological approach to cardiovascular prevention.
Does our swallow go to sleep? Changes in swallow function during sleep and implications for symptoms
Authors: Sato Kiminori
Published: October 2020

Purpose of review

Swallowing is a vital function and the clearance of the pharynx by deglutition, which removes matter that could be aspirated, and the respiratory phase patterns associated with deglutition are important in protecting the airways and lungs against aspiration. This article reviews swallowing and respiratory phase patterns associated with deglutition during sleep and their implications for pathophysiology.

Recent findings

During sleep, swallowing is infrequent and absent for long periods. The deeper the sleep stage, the lower the mean deglutition frequency. However, in healthy younger adults, sleep-related deglutition is almost always followed by arrested breathing and expiration, reducing the risk of aspiration. Deglutition is extremely infrequent as well as absent for long periods in the aged. Consequently, clearance of the pharynx and esophagus by deglutition was extremely reduced during sleep in the aged. Furthermore, respiratory phase patterns associated with deglutition displayed adverse patterns during sleep in the aged.

Due to the complexity of swallowing processes, many adverse health conditions can influence swallowing functions during sleep, especially in the aged. Sleep-related deglutition and respiratory phase patterns may adversely influence aspiration-related diseases such as aspiration pneumonia, especially in the aged not only with primary but also with secondary presbyphagia.
Chemotherapy and dysphagia: the good, the bad, the ugly
Authors: Dewan Karuna
Published: October 2020

Purpose of review

Dysphagia is a debilitating, depressing and potentially life-threatening complication in cancer patients that is likely underreported. The purpose of this review is to critically synthesize the current knowledge regarding the impact of chemotherapeutic regimens on swallowing function.

Recent findings

Those patients with cancers involving the aerodigestive tract, head and neck cancer and oesophageal cancer are at highest risk of developing dysphagia. The most common dysphagia causing toxicity of chemotherapeutic agents is mucositis/stomatitis. The use of cisplatin is correlated with increased incidence of mucositis. Similarly, the addition of melphalan is also associated with worsening mucositis and dysphagia. In some cases of oesophageal cancer, thyroid cancer, metastatic lung or breast cancer the use of chemotherapy can improve swallow function as obstructive lesions are reduced.

There is limited literature regarding the role of chemotherapy in the development or treatment of dysphagia. Most dysphagia that occurs during cancer treatment is attributable to radiation or the synergistic effect of radiation and chemotherapy. Patients with disordered swallowing prior to treatment have the greatest risk of developing posttreatment dysphagia. Studies are needed to determine whether acute inflammation associated with oropharyngeal mucositis predisposes for late dysphagia.
SMARCA4/SMARCA2-deficient Carcinoma of the Esophagus and Gastroesophageal Junction
Authors: Horton Rachel K. , Ahadi Mahsa , Gill Anthony J. , Said Samar , Chen Zongming E. , Bakhshwin Ahmed , Nichols Meredith , Goldblum John R. , Graham Rondell P.
Published: October 2020

Undifferentiated carcinoma of the esophagus and gastroesophageal junction is a recently recognized entity in the fifth edition of the World Health Organization Classification of Digestive Tumors and is diagnostically challenging, particularly on small biopsies. SMARCA4 and SMARCA2 are chromatin remodeling genes with key roles in oncogenesis. We retrieved 14 cases of SMARCA4/SMARCA2-deficient undifferentiated carcinoma of the gastroesophageal junction and esophagus from the authors’ institutions. The tumors showed similar histologic findings: the sheet-like proliferation of tumor cells characterized by discohesion, large nuclei, and prominent macronucleoli with many tumor cells exhibiting a rhabdoid appearance. In 8 cases, adjacent specialized intestinal metaplasia was noted and 3 cases exhibited adjacent high-grade dysplasia. Immunohistochemically, tumors variably expressed keratins and disclosed loss of expression of SMARCA4 in 12 and SMARCA2 in 7 cases. In 2 cases SMARCA2 alone was lost without SMARCA4 loss. A mutant p53 immunohistochemical pattern was seen in 4 of 4 cases, 3 of which showed diffuse, strong nuclear expression, and 1 case displayed a complete loss of nuclear expression of p53, including invasive carcinoma and associated dysplasia, when present. Limited clinical follow-up was available, but 3 patients died of disease within 0.6, 2, and 7 months of diagnosis. We present the first series of undifferentiated carcinoma of the esophagus and gastroesophageal junction with this characteristic morphology associated with loss of SMARCA4 and/or SMARCA2 expression. This tumor type likely arises from dedifferentiation of a lower grade carcinoma in some cases, and Barrett esophagus and appears to be associated with an aggressive clinical course.
A Hybrid Model of Pediatric and Adult Critical Care During the Coronavirus Disease 2019 Surge: The Experience of Two Tertiary Hospitals in London and New York
Authors: Deep Akash , Knight Philip , Kernie Steven G. , D’Silva Pam , Sobin Brittany , Best Thomas , Zorrilla Maria , Carson Lydia , Zoica Bogdana , Ahn Danielle
Published: October 2020

Objectives:

The current novel severe acute respiratory syndrome coronavirus 2 outbreak has caused an unprecedented demand on global adult critical care services. As adult patients have been disproportionately affected by the coronavirus disease 2019 pandemic, pediatric practitioners world-wide have stepped forward to support their adult colleagues. In general, standalone pediatric hospitals expanded their capacity to centralize pediatric critical care, decanting patients from other institutions. There are few units that ran a hybrid model, managing both adult and pediatric patients with the same PICU staff. In this report, we describe the hybrid model implemented at our respective institutions with shared experiences, pitfalls, challenges, and adjustments required in caring for both young and older patients.

Design:

Retrospective cohort study.

Setting:

Two PICUs in urban tertiary hospitals in London and New York.

Patients:

Adult and pediatric patients admitted to the PICU in roughly a 6-week period during the coronavirus disease 2019 surge.

Interventions:

None.

Measurements and Main Results:

The PICU at King’s College Hospital admitted 23 non-coronavirus disease adult patients, while whereas the PICU at Morgan Stanley’s Children Hospital in New York admitted 46 adults, 30 of whom were coronavirus disease positive. The median age of adult patients at King’s College Hospital was higher than those admitted in New York, 53 years (19–77 yr) and 24.4 years (18–52 yr), respectively. Catering to the different physical, emotional, and social needs of both children and adults by the same PICU team was challenging. One important consideration in both locations was the continued care of patients with severe non-coronavirus disease–related illnesses such as neurosurgical emergencies, trauma, and septic shock. Furthermore, retention of critical specialists such as transplant services allowed for nine and four solid organ transplants to occur in London and New York, respectively.

Conclusions:

This hybrid model successfully allowed for the expansion into adult critical care while maintaining essential services for critically ill children. Simultaneous care of adults and children in the ICU can be sustained if healthcare professionals work collaboratively, show proactive insight into anticipated issues, and exhibit clear leadership.
Substantial Decline in Use of HIV Preexposure Prophylaxis Following Introduction of COVID-19 Physical Distancing Restrictions in Australia: Results From a Prospective Observational Study of Gay and Bisexual Men
Authors: Hammoud Mohamed A. , Grulich Andrew , Holt Martin , Maher Lisa , Murphy Dean , Jin Fengyi , Bavinton Benjamin , Haire Bridget , Ellard Jeanne , Vaccher Stefanie , Saxton Peter , Bourne Adam , Degenhardt Louisa , Storer Daniel , Prestage Garrett
Published: October 2020

Background:

In response to the novel coronavirus disease (COVID-19) pandemic, Australia introduced public health and physical distancing restrictions in late March 2020. We investigated the impact of these restrictions on HIV preexposure prophylaxis (PrEP) use among Australian gay and bisexual men (GBM).

Methods:

Participants in an ongoing online cohort study previously reported PrEP use from 2014 to 2019. In April 2020, 847 HIV-negative and untested participants completed questionnaires assessing changes in PrEP use as a result of COVID-19 public health measures. Binary logistic multiple regression was used to estimate adjusted odds ratios (aOR) and 95% confidence intervals (95% CI) to compare changes in PrEP use behaviors.

Results:

Among 847 men, mean age was 44.1 years (SD: 12.7). PrEP use rose from 4.9% in 2015 to 47.2% in 2020. Among those, 41.8% (n = 167) discontinued PrEP use during COVID-19 restrictions. Discontinuing PrEP during COVID-19 restrictions was independently associated with being less likely to have recently tested for HIV (aOR: 0.17; 95% CI: 0.09 to 0.34; P < 0.001) and less likely to report sex with casual partners (aOR: 0.28; 95% CI: 0.14 to 0.54; P < 0.001).

Conclusions:

By April 2020, following the introduction of COVID-19 restrictions, GBM dramatically reduced PrEP use, coinciding with a reduction in sexual activity. Longer-term impacts of COVID-19 restrictions on sexual behaviors among GBM need to be monitored because they may foreshadow fluctuations in prevention coverage and risk of HIV infection. Our findings indicate a potential need for clear, targeted information about resumption of PrEP and on-demand optimal dosing regimens in response to ongoing changes in restrictions.
COVID-19 in children: current evidence and key questions
Authors: Munro Alasdair P.S. , Faust Saul N.
Published: October 2020

Purpose of review

SARS-CoV-2 infection in children has been less well characterized than in adults, primarily due to a significantly milder clinical phenotype meaning many cases have gone undocumented by health professionals or researchers. This review outlines the current evidence of the epidemiology of infection in children, the clinical manifestations of disease, the role of children in transmission of the virus and the recently described hyperinflammatory syndrome observed later during the first phase of the pandemic.

Recent findings

International seroprevalence studies have found younger children to have lower prevalence of antibodies to SARS-CoV-2, indicating they have not been infected as much as adults. This may be due to shielding by school closures, or by a reduced susceptibility to infection, as indicated by a significantly lower attack rate in children than adults in household contact tracing studies. The most well recognized symptoms in adults of cough, fever, anosmia and ageusia are less frequent in children, who may often present with mild and nonspecific symptoms, or with gastrointestinal symptoms alone. Risk factors for severe disease in children include chronic lung, cardiac or neurological disease, and malignancy. However, the absolute risk still appears very low for these cohorts. A new hyperinflammatory syndrome has emerged with an apparent immune cause.

Important questions remain unanswered regarding why children have mild disease compared with adults; how children of different ages contribute to asymptomatic community transmission of the virus; and the pathophysiology of and most appropriate investigation and treatment strategies for the novel hyperinflammatory syndrome.