bluuebunny/crossref_metadata_2025 huggingface dataset:
Mechnetor: a web server for exploring protein mechanism and the functional context of genetic variants
Authors: González-Sánchez Juan Carlos , Ibrahim Mustafa F R , Leist Ivo C , Weise Kyle R , Russell Robert B
Published: May 2021

Advances in DNA sequencing and proteomics mean that researchers must now regularly interrogate thousands of positional gene/protein changes in order to find those relevant for potential clinical application or biological insights. The abundance of already known information on protein interactions, mechanism, and tertiary structure provides the possible means to understand these changes rapidly, though a careful and systematic integration of these diverse datasets is first needed. For this purpose, we developed Mechnetor, a tool that allows users to quickly explore and visualize integrated mechanistic data for proteins or interactions of interest. Central to the system is a careful cataloguing of diverse sources of protein interaction mechanism, and an efficient means to visualize interactions between relevant and/or known protein regions. The result is a finer resolution interaction network that provides more immediate clues as to points of intervention or mechanistic understanding. Users can import protein, interactions, genetic variants or post-translational modifications and see these data in the best known mechanistic context. We demonstrate the tool with topical examples in human genetic diseases and cancer genomics. The tool is freely available at: mechnetor.russelllab.org.
The Cell Fate Controlling CLE40 Peptide Requires CNGCs to Trigger Highly Localized Ca2+ Transients inArabidopsis thalianaRoot Meristems
Authors: Breiden Maike , Olsson Vilde , Blümke Patrick , Schlegel Jenia , Gustavo-Pinto Karine , Dietrich Petra , Butenko Melinka A , Simon Rüdiger
Published: May 2021

Communication between plant cells and their biotic environment largely depends on the function of plasma membrane localized receptor-like kinases (RLKs). Major players in this communication within root meristems are secreted peptides, including CLAVATA3/EMBRYO SURROUNDING REGION40 (CLE40). In the distal root meristem, CLE40 acts through the RLK ARABIDOPSIS CRINKLY4 (ACR4) and the leucine-rich repeat (LRR) RLK CLAVATA1 (CLV1) to promote cell differentiation. In the proximal meristem, CLE40 signaling requires the LRR receptor-like protein CLAVATA2 (CLV2) and the membrane localized pseudokinase CORYNE (CRN) and serves to inhibit cell differentiation. The molecular components that act immediately downstream of the CLE40-activated receptors are not yet known. Here, we show that active CLE40 signaling triggers the release of intracellular Ca2+ leading to increased cytosolic Ca2+ concentration ([Ca2+]cyt) in a small subset of proximal root meristem cells. This rise in [Ca2+]cyt depends on the CYCLIC NUCLEOTIDE GATED CHANNELS (CNGCs) 6 and 9 and on CLV1. The precise function of changes in [Ca2+]cyt is not yet known but might form a central part of a fine-tuned response to CLE40 peptide that serves to integrate root meristem growth with stem cell fate decisions and initiation of lateral root primordia.
An Innovative Model Integrating an Academic-Practice Partnership in an RN-BSN Program
Authors: Katz Kathi S. , Czerwinski Sandra J. , Lockett Leslie J. , Munro Jacqueline C. , Gwartney Tiffany S. , Gore Teresa
Published: May 2021

Research demonstrates a higher concentration of bachelor of science in nursing (BSN)-prepared registered nurses improves patient care outcomes. To increase the BSN workforce, one academic institution, in collaboration with a practice partner, formed an academic-practice partnership. Strategic actions included the development of the integration model for the RN-BSN program as a framework for program expansion, curricular revision, nurse leader faculty integration, and student clinical placement. Partnership outcomes included the acceptance of all qualified applicants for admission, clinical placement secured for all students, excellent course evaluation ratings for faculty, and development of a sustainable and transferrable model.
Role of clinical history in beta-lactam hypersensitivity
Authors: Plager Jessica , Judd Allen , Blumenthal Kimberly
Published: May 2021

Purpose of Review

Understand how the clinical history has been used to risk stratify patients reporting a beta-lactam allergy, both in clinical care pathways and predictive models.

Recent findings

Drug allergy clinical care pathways have emerged as a safe and effective method of stratifying patients with a reported beta-lactam allergy into risk categories, with ‘low-risk’ patients able to proceed straight to direct challenges or test doses. These methods have streamlined antibiotic stewardship policies and penicillin allergy de-labeling. However, how to define ‘low-risk’ has been subject to much debate. New research has developed predictive models that utilize the clinical history to assess a patient's true risk of beta-lactam allergy.

The clinical history has long been an essential part of drug allergy evaluation and has proven invaluable within the past decade in the development of drug allergy clinical pathways. Evidence-based predictive models that use the clinical history to assess a patient's true risk of beta-lactam allergy offer tremendous promise, but differ in crucial areas such as the populations they study, the predictor variables they use, and the ultimate accuracy they attain. These models highlight key aspects of the drug allergy history and pave the way for future large-scale research.
Frameworks for trainee education in the nonoperating room setting
Authors: Beal Benjamin , Du Austin L. , Urman Richard D. , Gabriel Rodney A.
Published: May 2021

Purpose of review

As the volume and types of procedures requiring anesthesiologist involvement in the nonoperating room anesthesia (NORA) setting continue to grow, it is important to create a formal curriculum and clearly define educational goals.

Recent findings

A NORA rotation should be accompanied by a dedicated curriculum that should include topics such as education objectives, information about different interventional procedures, anesthesia techniques and equipment, and safety principles. NORA environment may be unfamiliar to anesthesia residents. The trainees must also learn the principles of efficiency, rapid recovery from anesthesia, and timely room turnover. Resident education in NORA should be an essential component of their training. The goals and objectives of the NORA educational experience should include not only developing the clinical knowledge necessary to implement the specific type of anesthetic desired for each procedure, but also the practical knowledge of care coordination needed to safely and efficiently work in the NORA setting.

As educators, we must foster and grow a resident's resilience by continually challenging them with new clinical scenarios and giving them appropriate autonomy to take risks and move outside of their comfort zone. Residents should understand that exposure to such unique and demanding environment can be transformative.
Controversies in the Treatment of Acute Compartment Syndrome of the Foot
Authors: Bemenderfer Thomas B. , Anderson John B. , Maskill John D. , Bohay Donald B.
Published: May 2021

Acute compartment syndrome of the foot remains a controversial topic. The diagnosis, management, and reported sequelae remain largely supported by low level evidence and expert opinion. Ischemic plantar flexion contractures resulting in cavus and claw toe deformities, acute and chronic neuropathic pain, sensory deficits and paresthesias, neuropathic ulceration, and odynohyperkeratosis are sequelae of both conservative and operative management of acute compartment syndrome of the foot. Further research on the outcomes of acute fasciotomy versus delayed management is necessary to support therapeutic strategies. Level of Evidence: Diagnostic Level V. See Instructions for Authors for a complete description of levels of evidence.
C-reactive protein as a biomarker for immune-related adverse events in melanoma patients treated with immune checkpoint inhibitors in the adjuvant setting
Authors: Lauwyck Justine , Beckwée Aline , Santens Arno , Schwarze Julia Katharina , Awada Gil , Vandersleyen Valérie , Aspeslagh Sandrine , Neyns Bart
Published: May 2021

The objective of this study was to evaluate the utility of serum C-reactive protein (CRP) as biomarker for the early diagnosis of immune-related adverse events (irAEs) in melanoma patients treated with immune checkpoint inhibitors (ICIs) in the adjuvant setting, and its potential correlation with relapse-free survival (RFS). Prospectively collected data from 72 melanoma patients treated with adjuvant ICIs were pooled. CRP values at diagnosis of 10 irAEs were descriptively analysed. Correlations between RFS and the occurrence of irAEs, the grade of the irAE, the extent of CRP-elevation and the use of corticosteroids for irAE treatment were investigated. A total of 191 irAEs (grade 1/2, n = 182; grade 3/4, n = 9) occurred in 64 patients [skin toxicity (n = 70), fatigue (n = 50), thyroiditis (n = 12), musculoskeletal toxicity (n = 11), sicca syndrome (n = 10), other (n = 23), pneumonitis (n = 6), colitis (n = 4), hepatitis (n = 3) and hypophysitis (n = 2)]. In pneumonitis and hypophysitis, the median CRP levels at diagnosis exceeded the upper limit of normal (ULN, 5 mg/L). After a median follow-up of 26.5 months, 28 patients (39%) had been diagnosed with a melanoma relapse. Patients who experienced no irAE were at the highest risk for relapse (P = 0.008). A trend was observed for patients diagnosed with an irAE that was associated with an elevated CRP (>2xULN) to be at higher risk for relapse as compared to those diagnosed with an irAE and CRP <ULN (P = 0.054). CRP has potential as biomarker for the early detection of selected irAEs. Dynamic evaluation can guide irAE diagnosis, regression or relapse. The observed correlation between irAEs associated with an elevated CRP and risk for recurrence deserves further investigation.
Impact of dietary intake of sodium and potassium on short-term blood pressure variability
Authors: Chang Hao-Chih , Wu Chung-Li , Lee Yu-Hsuan , Gu Ya-Hui , Chen Yi-Ting , Tsai Yi-Wen , Chuang Shao-Yuan , Guo Chao-Yu , Chen Chen-Huan , Cheng Hao-Min
Published: May 2021

Background:

Dietary Approaches to Stop Hypertension (DASH)-Sodium trial showed that dietary sodium and potassium affect blood pressure (BP). We aimed to investigate whether dietary sodium and potassium affect short-term BP variability (BPV) in addition to BP.

Methods:

A total of 343 participants from the DASH-Sodium trial (age 48.4 ± 9.7, 42.5% men) and 323 individuals from the Jackson Heart Study (JHS) (age 56.7 ± 11.2, 30.7% men) with satisfactory ambulatory BP monitoring records and 24-h urine collection were included. Average real variability (ARV) was calculated as a measure of short-term BPV.

Results:

By estimating dietary intake from urinary excretion, we observed that higher urinary sodium-to-potassium ratio was significantly associated with higher diastolic ARV in both studies. Among the DASH-Sodium trial, potassium-rich DASH diet alone had insignificant effect on both systolic (−0.1 ± 1.7 mmHg, P = 0.343) or diastolic ARV (−0.2 ± 1.5 mmHg, P = 0.164), whereas combined DASH diet and low sodium intake significantly reduced both systolic (8.5 ± 1.6 vs. 8.9 ± 1.7 mmHg, P = 0.032) and diastolic ARV (7.5 ± 1.5 vs. 7.8 ± 1.6 mmHg, P = 0.025) as compared with control diet and high sodium intake. As the reduction of systolic ARV was majorly derived from the change of mean SBP, diastolic ARV was significantly determined by urinary sodium-to-potassium ratio (β coefficient ± standard error: 0.012 ± 0.004; P = 0.006) after adjusting for age, sex, smoking, mean DBP, BMI, and race.

Conclusion:

Dietary sodium and potassium can jointly modulate short-term BPV in addition to BP. Combined DASH diet and low sodium intake may reduce systolic and diastolic ARV via different mechanisms.
Clinical Features and Outcome of Children With Hereditary Spherocytosis
Authors: Kiliç Mehmet A. , Özdemir Gul N. , Tahtakesen Tuba N. , Gökçe Müge , Uysalol Ezgi P. , Bayram Cengiz , Ayçiçek Ali , Aydoğan Gönül
Published: May 2021

Objective:

The aim of this study was to evaluate the demographics, clinical, and laboratory findings and treatment responses of patients with hereditary spherocytosis (HS).

Materials and Methods:

Data of children with HS were examined. Diagnosis was based on clinical history, physical examination, family history, presence of spherocytes on peripheral blood smear, and osmotic fragility test.

Results:

A total of 101 patients were included. The median (range) age at diagnosis was 38.0 (1 to 188) months. Mild, moderate, and severe forms of HS were present in 29 (28.7%), 15 (14.9%), and 57 (56.4%) patients, respectively. Family history was available in 73 patients and 56 of these (76.7%) had a positive family history for HS. Forty-five (44.5%) patients needed regular transfusions and all of these had severe disease. Although most patients did not require transfusion postsplenectomy, 2 of 45 (4.4%) patients continued to require transfusion. Transfusion dependence was significantly (P<0.001) higher in patients with severe spherocytosis.

Conclusions:

In HS, splenomegaly, pallor, and jaundice are the most common clinical features. Splenectomy dramatically reduces hemolysis in most cases and virtually abolishes further requirement for transfusion.
Autologous Hematopoietic Stem Cell Transplant: A Potential Option for Relapsed Pediatric Acute Myeloid Leukemia With Lack of Matched Sibling Donor and Resource Challenge
Authors: Kalra Kaushal , Arora Shalabh , Verma Saurav , Pushpam Deepam , Bakhshi Sameer
Published: May 2021

Though allogeneic hematopoietic stem cell transplant (HSCT) is standard for relapsed pediatric acute myeloid leukemia, often it may not be accessible due to donor unavailability and resource limitations. We retrospectively analyzed outcomes of 26 children (mean age: 10.9±4.5 y) who underwent autologous HSCT in complete remission 2. Three-year event-free survival and overall survival were 50.1±10.7% and 63.3±9%, respectively; with 1 treatment-related death and 46% relapse rate. Notwithstanding the retrospective study design and somewhat favorable patient characteristics, the outcomes are comparable with those of other series and our own allogeneic HSCT data. Autologous HSCT is a potential alternative to allogeneic HSCT, especially in countries with poorly maintained donor registries.
A Feasibility Pilot Study of Online Modules of Hydroxyurea and Sickle Cell Disease Care for Adolescents and Young Adults for Family Medicine Residents
Authors: Dawson Amy , Mullen Kelly , Janson Isaac A. , Henriksen Brian , Duncan Natalie , O’Brien Dennis , Meier Emily R.
Published: May 2021

Family medicine (FP) residency programs are located throughout Indiana, and most adults with sickle cell disease (SCD) in Indiana have access to a primary care clinic administered by a FP program. Allen County ranks third in SCD incidence in Indiana, but has few providers for adolescents, young adults (AYAs) and adults with SCD. Initiation of a novel partnership between Indianapolis-based adult hematologists (130 miles distant), and the FP program in Allen County aimed to educate FP residents about SCD, hydroxyurea, transition, and SCD complications. To determine the feasibility of utilizing online learning modules to educate FP residents about SCD care in AYA and adults, 3 online learning modules (comprehensive care of AYAs with SCD, hydroxyurea, and best practices in AYA transition) were developed and continuing medical education-accredited. Electronic pretest and posttest were distributed to 32 FP residents to test the retention of content through an Institutional Review Board approved protocol. This pilot study demonstrates that it is feasible to utilize online educational modules to educate providers about SCD care.
Clinical Utilities of Electrocardiography in the Diagnosis of Myocardial Ischemia in Children With Sickle Cell Anemia: Correlation With Serum Cardiac Troponin I
Authors: Adeniyi Adewuyi T. , Okeniyi John A.O. , Adegoke Samuel A. , Oseni Saheed B.A. , Smith Olufemi S. , Abe-Dada Adedolapo A.
Published: May 2021

Background:

Sickle cell anemia (SCA) is associated with recurrent vaso-occlusive crisis (VOC) and the risk of myocardial ischemia (MI). This study investigated the utility of electrocardiography (ECG) and cardiac troponin I (cTnI) in diagnosing MI during VOC.

Materials and Methods:

Children with SCA 5 to 15 years of age in VOC (patients) and age-matched and sex-matched steady-state controls were studied. Their ECG and cTnI levels were measured at contact and after 4 to 6 weeks.

Results:

One hundred eighty-six children (93 patients and 93 controls) were studied. The mean (SD) ages of the patients and controls were 8.8 (3.2) and 9.0 (3.1) years, respectively. The mean MI score was significantly higher for the patients, 1.7 (1.2), than the controls, 1.3 (1.0), P=0.002. A significantly higher proportion of the patients, 18 (19.4%), also had significant ischemia compared with the controls, 8 (8.6%), P=0.016. The median (interquartile range) serum cTnI level was significantly higher in the patients than the controls, P=0.006. All 7 of the patients with elevated cTnI had VOC. No significant correlation was found between MI score and cTnI in both groups.

Conclusions:

cTnI is elevated and ECG features of MI worsen during VOC. Longitudinal studies to investigate their evolvement over time are advocated.
A 5-Year Retrospective Study on Infant Homicide Presenting as Cot Death
Authors: Tse Rexson , Ioelu Leilani , Chen Matthew , McCarthy Sinead , Glenn Charley , Kesha Kilak , Morrow Paul , Stables Simon
Published: May 2021

Being found dead in cot or bed is the most common presentation encountered with infant deaths. These deaths are often associated with unsafe sleep environment. The postmortem examination in such cases is often negative, and along with family objections, cultural, and other factors, may lead to a coroner considering not authorizing a postmortem examination. However, not identifying a homicide is a potential risk if a postmortem examination is not performed. This 5-year retrospective study investigated the proportion of infant homicide death initially presenting as cot death. Of a total of 103 cases of infants initially presenting as being found dead in cot or bed, 3 (approximately 3%) were classified as homicides after postmortem examination. During the study period, a total of 9 infant homicides were reported, translating to 33% (3 of 9) of infant homicides presented as cot deaths. Postmortem radiology was a valuable adjunct, but was unable to recognize 2 of the homicide cases with traumatic head injuries (with subdural hemorrhage and brain injury only). We strongly advocate that all infant deaths presenting as cot death require a full postmortem examination.
Left Heart Decompression on Veno-Arterial Extracorporeal Membrane Oxygenation in Children With Dilated Cardiomyopathy and Myocarditis: An Extracorporeal Life Support Organization Registry Review
Authors: Choudhury Tarif A. , Ofori-Amanfo George , Choi Jaeun , Eisenberg Ruth E. , Rycus Peter , Medar Shivanand S. , Aydin Scott I.
Published: May 2021

OBJECTIVES:

To describe the association between left heart decompression on veno-arterial extracorporeal membrane oxygenation and survival in patients with myocarditis and dilated cardiomyopathy. The secondary outcome is to study association of left heart decompression with survival in children with myocarditis compared with those with dilated cardiomyopathy.

DESIGN:

Retrospective study of a multicenter registry database.

SETTING:

Data reported to Extracorporeal Life Support Organization from international extracorporeal membrane oxygenation centers.

PATIENTS:

Patients less than or equal to 18 years old with a diagnosis of myocarditis or dilated cardiomyopathy receiving extracorporeal membrane oxygenation.

INTERVENTIONS:

None.

MEASUREMENTS AND MAIN RESULTS:

A total of 1,438 pediatric extracorporeal membrane oxygenation runs were identified. Thirty-seven percent of the patients had myocarditis (n = 532), whereas the rest had dilated cardiomyopathy. Survival to hospital discharge was 63%. Median extracorporeal membrane oxygenation duration was 148 hours with interquartile range (84–248 hr). Nineteen percent of patients (n = 274) had left heart decompression. Multivariable analysis revealed using left heart decompression (adjusted odds ratio, 1.42; 95% CI, 1.06–1.89; p = 0.02), e-cardiopulmonary resuscitation (adjusted odds ratio, 0.63; 95% CI, 0.51–0.79; p < 0.001), higher pH (adjusted odds ratio, 3.69; 95% CI, 1.80–7.53; p < 0.001), and diagnosis of myocarditis (adjusted odds ratio, 1.69; 95% CI, 1.35–2.08; p < 0.001) were associated with greater odds of survival. In the multivariable analysis for patients with dilated cardiomyopathy, left heart decompression failed to reveal a significant association with survival (20% among survivors vs 17% among nonsurvivors, 95% CI, –2.2% to 8.0%). Meanwhile in patients with myocarditis, the multivariable analysis failed to exclude the possibility that left heart decompression was associated with up to a three-fold greater odds of survival (adjusted odds ratio, 1.77; 95% CI, 0.99–.15).

CONCLUSIONS:

Retrospective review of the Extracorporeal Life Support Organization registry revealed an association between left heart decompression and greater odds of survival in children with myocarditis and dilated cardiomyopathy on extracorporeal membrane oxygenation. When comparing patients with dilated cardiomyopathy against those with myocarditis, we could not exclude a three-fold greater odds of survival associated with the use of left heart decompression. This finding warrants further prospective evaluation.
Neurological Complications Acquired During Pediatric Critical Illness: Exploratory “Mixed Graphical Modeling” Analysis Using Serum Biomarker Levels
Authors: Raghu Vineet K. , Horvat Christopher M. , Kochanek Patrick M. , Fink Ericka L. , Clark Robert S. B. , Benos Panayiotis V. , Au Alicia K.
Published: May 2021

OBJECTIVES:

Neurologic complications, consisting of the acute development of a neurologic disorder, that is, not present at admission but develops during the course of illness, can be difficult to detect in the PICU due to sedation, neuromuscular blockade, and young age. We evaluated the direct relationships of serum biomarkers and clinical variables to the development of neurologic complications. Analysis was performed using mixed graphical models, a machine learning approach that allows inference of cause-effect associations from continuous and discrete data.

DESIGN:

Secondary analysis of a previous prospective observational study.

SETTING:

PICU, single quaternary-care center.

PATIENTS:

Individuals admitted to the PICU, younger than18 years old, with intravascular access via an indwelling catheter.

INTERVENTIONS:

None.

MEASUREMENTS:

About 101 patients were included in this analysis. Serum (days 1–7) was analyzed for glial fibrillary acidic protein, ubiquitin C-terminal hydrolase-L1, and alpha-II spectrin breakdown product 150 utilizing enzyme-linked immunosorbent assays. Serum levels of neuron-specific enolase, myelin basic protein, and S100 calcium binding protein B used in these models were reported previously. Demographic data, use of selected clinical therapies, lengths of stay, and ancillary neurologic testing (head CT, brain MRI, and electroencephalogram) results were recorded. The Mixed Graphical Model-Fast-Causal Inference-Maximum algorithm was applied to the dataset.

MAIN RESULTS:

About 13 of 101 patients developed a neurologic complication during their critical illness. The mixed graphical model identified peak levels of the neuronal biomarker neuron-specific enolase and ubiquitin C-terminal hydrolase-L1, and the astrocyte biomarker glial fibrillary acidic protein to be the direct causal determinants for the development of a neurologic complication; in contrast, clinical variables including age, sex, length of stay, and primary neurologic diagnosis were not direct causal determinants.

CONCLUSIONS:

Graphical models that include biomarkers in addition to clinical data are promising methods to evaluate direct relationships in the development of neurologic complications in critically ill children. Future work is required to validate and refine these models further, to determine if they can be used to predict which patients are at risk for/or with early neurologic complications.
Cardiovascular Risk Assessment in Women With Rheumatoid Arthritis Through Carotid and Femoral Artery Doppler Ultrasound
Authors: Sacilotto Nathália de Carvalho , Augusto André Ozela , Lucena Dayrana Alves , Godoy Marcos Roberto , Almeida Rogério Duque de , Pernambuco Roberta de Almeida , Lima Sônia Maria Alvarenga Anti Loduca , Sacilotto Roberto , Giorgi Rina Dalva Neubarth
Published: May 2021

Objective

The aims of this study were to assess cardiovascular risk in patients with rheumatoid arthritis (RA) classified as low-risk by the Framingham score, before and after the multiplication by 1.5 recommended by the European League Against Rheumatism (EULAR), and to stratify them using carotid and femoral Doppler ultrasound (DUS) in order to optimize the assessment of the asymptomatic cardiovascular disease incidence.

Methods

Thirty-five female patients with RA and 35 healthy women (control group), both with low cardiovascular risk by Framingham score, were enrolled in the study (randomized). All of them underwent carotid and femoral DUS studies.

Results

The mean age at diagnosis was 44.57 years, the mean disease duration was 12.11 years and the mean disease activity score according to the Disease Activity Score 28 was 1.91, whereas according to the Clinical Disease Activity Index, it was 6.176. The sample was homogeneous. Within the RA group, 46% showed changes in the carotid and/or femoral DUS, compared with 14% in the control group (p = 0.004). Of the DUS with abnormalities, in the RA group, 31% of the carotid DUS and 81% of the femoral DUS (p = 0.005) showed intima-media thickness and/or atherosclerotic plaques. After EULAR 1.5 multiplication factor, 66% remained low cardiovascular risk. Of these, 35% of the patients showed changes in the carotid and/or femoral DUS, compared with 14% of the control group (p = 0.07).

Conclusions

The EULAR criteria are effective at identifying patients with high cardiovascular risk. Carotid DUS and, especially, femoral DUS are tools that can be used in clinical practice as ways to detect CVD even in its asymptomatic form.
Comparison of Sound Touch Elastography, Sound Touch Quantify, and 4 Serum Fibrosis Indexes for the Diagnosis of Liver Fibrosis in Patients With Chronic Hepatitis B
Authors: Dong Bingtian , Huang Shu , Chang Jiandong , Chen Xiaoyan , Yan Jianping
Published: May 2021

The aim of this research was to compare the use of shear wave elastography (sound touch elastography [STE] and sound touch quantify [STQ]) and serum liver fibrosis indexes in the evaluation and staging of chronic hepatitis B (CHB) liver fibrosis. Sound touch elastography is a form of 2-dimensional shear wave elastography, and STQ is a form of point shear wave elastography. Between June 2018 and March 2019, 122 patients with CHB were assessed using STE and STQ. Serum liver biomarkers tests were undertaken, and liver biopsy was performed, and these were used to assign a pathological stage based on the Scheuer scoring system. A receiver operating characteristic curve was used to analyze the diagnostic value of noninvasive methods for evaluating and staging liver fibrosis. The cutoff values of STE for liver fibrosis stages S2 to S4 were 8.85, 9.97, and 10.29 kPa, respectively, and the areas under the receiver operating characteristic (AUCs) curve were 0.703, 0.821, and 0.900, respectively. The cutoff values of STQ for liver fibrosis stages S2 to S4 were 11.31, 13.81, and 20.60 kPa, respectively, and the AUCs were 0.674, 0.807, and 0.893, respectively. The AUCs of STE and STQ in diagnosing fibrosis stage were significantly higher than those of liver serum biomarkers (P < 0.05). The AUCs for the ability of the aspartate transaminase-to-platelet ratio index, the fibrosis index based on the 4 factors, the King score, and the Forns index to diagnose S2 fibrosis were 0.502, 0.624, 0.542, and 0.616, respectively, and the AUCs for their ability to diagnose S4 fibrosis were 0.856, 0.861, 0.883, and 0.823, respectively. Both STE and STQ are noninvasive methods for the assessment of liver fibrosis in CHB patients, with better diagnostic performances than those of 4 serum fibrosis indexes.
Real-Time Tissue Elastography to Evaluate Hepatic Hypoxic-Ischemic Injury Caused by Brain Death
Authors: Zhang Guoying , Tang Ying , Yu Huimin , Kong Weina , Chen Yun , Liu Yang , Zhao Jingwen
Published: May 2021

This study aimed to explore the potential of real-time tissue elastography (RTE) in evaluating hepatic hypoxic-ischemic injury caused by brain death. We performed RTE and biopsy for 50 donated liver. Hematoxylin-eosin staining was used to observe hepatocyte acidophilic change. Liver grafts were divided into 2 groups, one nonacidophilic change (n = 7) and the other with acidophilic change (n = 43). Correlation and difference analysis were performed for hematoxylin-eosin staining results and RTE parameters. The result indicated that 4 of the 11 RTE parameters, namely, the area of low strain within the region of interest (%AREA), contrast (CONT), inverse difference moment (IDM), and correlation (CORR) were related to hepatocytes acidophilic change (r = 0.284, P = 0.046; r = 0.349, P = 0.013; r = −0.444, P = 0.001; r = −0.381, P = 0.00). Whereas %AREA and CONT of the nonacidophilic change group were lower than that of the acidophilic change group (P < 0.05), IDM and CORR in nonacidophilic change group were higher than that of the acidophilic change group (P < 0.05); the remaining parameters were not statistically different between 2 groups (P > 0.05). Analysis of receiver operating characteristic curve indicated that the area under the curve of %AREA, CONT, IDM, and CORR were 0.75, 0.79, 0.81, and 0.77, respectively. Based on this, we concluded that the quantitative analysis parameters of RTE could preliminary assess hepatic hypoxic-ischemic injury caused by brain death.
Ultrasound Elastography in the Differentiation of Simple Cyst and Type I Hydatid Cyst of the Liver
Authors: Durmaz Fatma , Ozgokce Mesut , Turkoglu Saim , Dundar İlyas , Goya Cemil
Published: May 2021

Hydatid cyst (HC) is a parasitic disease that is endemic particularly to the sheep-breeding regions of the world, our country included. Given their propensity to materialize most commonly in the liver, our study evaluates the value of ultrasound elastography in the differential diagnosis of simple cyst and type I HCs of the liver.

The study involved a total of 73 cysts (22 simple cysts, 51 type I HCs) that were removed using the puncture aspiration injection reaspiration technique between 2016 and 2018. All measurements were made using a Siemens ACUSON S2000 (Siemens Healthcare, Erlangen, Germany) device with a 4-MHZ 4C1 convex probe, an acoustic radiation force impulse elastography procedure, and a Virtual Touch IQ option. The difference between the mean shearwave elastography (SWE) values of both groups was analyzed with an independent t test.

Of the 70 patients involved in the study, 29 were female and 41 were male, with a mean ± SD age of 38.85 ± 17.62 years (range, 5–82 years). Upon the examination of the 22 simple cysts and the 51 HCs, the mean ± SD SWE values were found to be 2.6 ± 0.96 (0.96–4.25) and 2.8 ± 1.69 (0.66–4.84), respectively. No statistically significant difference was identified between the SWE values of type I HCs and simple cysts (P > 0.005).

Although HCs and simple cysts had similar radiological appearances, and a relative difference was noted in the differentiation of the elastographic measurements, this difference was not statistically significant. Accordingly, more comprehensive and various studies are needed.
Minimal Dissection Direct Frontalis Muscle Advancement Flap for Congenital Ptosis Repair
Authors: Dallalzadeh Liane O. , Park Kathryn S. , Korn Bobby S. , Kikkawa Don O. , Liu Catherine Y.
Published: May 2021

Background:

Frontalis flap advancement is an alternative means of congenital ptosis repair from frontalis suspension utilizing autologous fascia or allogenic implants. Variations in technique, including flap division, location and number of skin incisions, and dissection planes, are described in the literature.

Materials and Methods:

A retrospective case series of patients with congenital myogenic ptosis treated with simplified, minimal dissection frontalis flap advancement involving a single upper eyelid crease incision with dissection in the preseptal and subcutaneous planes without division to mobilize the frontalis flap. Inclusion criteria: pediatric patients age < 18 years with either primary or recurrent congenital ptosis following previous surgical repair. Exclusion criteria: ptosis of neurogenic etiology or postoperative follow-up < 3 months. Primary outcome measures were postoperative margin-reflex distance 1 (MRD1), the difference in MRD1 between surgical and nonsurgical eyelids in unilateral ptosis, and lagophthalmos. Secondary outcome measures included recurrence and complications.

Results:

Twenty-six patients met inclusion criteria, 24 males and 2 females. Mean postoperative MRD1 at last follow-up was 2.9 ± 1.2 mm and the mean difference in MRD1 between surgical and nonsurgical eyelids at last follow-up was 1.1 ± 1.0 mm. Average lagophthalmos at postoperative month 2 to 5 was 0.6 ± 0.7 mm. One patient demonstrated postoperative lid retraction that required re-operation. Four of 31 eyelids (12.9%) demonstrated ptosis recurrence at 5, 12, or 24 months.

Conclusions:

In this retrospective series, the authors report clinically and statistically significant surgical eyelid height improvement and symmetry between nonsurgical and surgical eyelids in congenital ptosis patients treated with minimal dissection direct frontalis flap advancement.
Impact of the Craniofacial Surgery Simulation in Anterior Plagiocephaly on Orbits and Oculomotor Muscles: Biomechanical Analysis With a Finite Element Model
Authors: Dalmas Florian , Thollon Lionel , Beylerian Marie , Godio Raboutet Yves , David Thierry , Scavarda Didier , Denis Danièle , Pech-Gourg Grégoire
Published: May 2021

Purpose:

The aim of this study was to show the displacements and strain induced by the supraorbital band advancement during a craniofacial surgery for an anterior plagiocephaly on the orbital bones and the orbital content thanks to a numerical surgical simulation using the finite element method.

Methods:

A three-dimensional (3D) finite element model of a child with an anterior plagiocephaly was entirely created from a tomodensitometry of a patient followed by our Craniofacial Pediatric team. Data of the tomodensitometry were computed with Slicer 3D to re-create the orbit geometry. Mesh production, properties of the model, and simulations of the fronto-orbital advancement were conducted on Hyperworks software (Altair Engineering, Inc., Detroit, MI, USA).

Results:

The resulting 3D Finite Element Model was used to perform the supraorbital advancement simulation. Displacement and strain patterns were studied for orbital bones, oculomotor muscles, and eyeballs. Relative high strain in the both trochlear area and excycloration of the right orbit are among the most interesting results as torsional strabismus as V-pattern strabismus are often described in children with an anterior plagiocephaly.

Conclusions:

This pediatric Finite-Element Model of both orbits of a child with an anterior plagiocephaly showed the impact of the fronto-orbital advancement on the oculomotor system. This model described the relationship between the craniofacial surgery and the strabismus in the unilateral coronal synostosis. The advantages of this model are the many opportunities for improvement, including postoperative period and additional surgical procedures.
Establishment of a C57BL/6 Mandibular Critical-Size Bone Defect Model
Authors: Yu Fei , Liu Lu , Xia Lunguo , Fang Bing
Published: May 2021

Purpose:

The goal of this study was to identify bone defects of critical size in C57BL/6 mouse mandibles.

Materials and Methods:

Twenty-four male mice were included in this study. All mice underwent surgeries on their left mandibles. Mandibular defects of 1.0 mm (n = 8), 1.6 mm (n = 8), and 2.3 mm (n = 8) were created. For the investigation of bone healing after an 8-week period, micro-computed tomography scans and histomorphology were performed.

Results:

Mandibular bone nonunions were seen 0/8 in the 1.0-mm group, 6/8 in the 1.6-mm group, and 8/8 in the 2.3-mm group. The outcome of micro-computed tomography showed that, after 8 weeks, the bone mineral density and the bone volume to total volume ratio were significantly different among the 3 groups. The defect gaps in the nonunion 1.6- and 2.3-mm groups were filled with connective tissue, and no obvious bone formation was found. Additionally, in quantitative analysis, according to the new bone fill calculations, the percentages were 91.85% ± 8.03% in the 1.0-mm group, 59.84% ± 20.60% in the 1.6-mm group, and 15.36% ± 8.28% in the 2.3-mm group, which indicated statistically significantly lower defect healing in the 2.3-mm group.

Conclusions:

The creation of 2.3-mm mandibular defects produces osseous nonunion in C57BL/6 mice.
Patient and Relative Experiences and Decision-making About Genetic Testing and Counseling for Familial ALS and FTD
Authors: Crook Ashley , Jacobs Chris , Newton-John Toby , Richardson Ebony , McEwen Alison
Published: May 2021

Genetic testing and counseling is an emerging part of care for patients with amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) and their families. This scoping review aimed to map patients’ and relatives’ experiences of genetic testing and counseling for familial ALS and FTD and the factors influencing their decision to proceed with testing or counseling. Informed by the Joanna Briggs Institute methodology, 5 databases were systematically searched. Thirty studies from 39 references were included. A descriptive numerical summary analysis and narrative synthesis was conducted. Mostly positive diagnostic testing experiences were reported, but issues arose due to progressive disease and discordant results. Predictive testing impacted at-risk relatives, regardless of the result received, and psychosocial sequelae ranged from relief to guilt, worry or contemplating suicide. Four reproductive testing experiences were reported. Personal, familial and practical factors, and the lived experience of disease, informed decision-making. Greater uncertainty and complexity may be faced in familial ALS/FTD than in other late-onset neurodegenerative diseases due to clinical and genetic heterogeneity, and testing limitations. Genetic counseling models of care should consider this difference to ensure that individuals with, or at risk of, ALS/FTD are effectively managed. Implications for research and practice are discussed.
Update on neuroimaging in disorders of consciousness
Authors: Sanz Leandro R.D. , Thibaut Aurore , Edlow Brian L. , Laureys Steven , Gosseries Olivia
Published: May 2021

Purpose of review

Neuroimaging has acquired a prominent place in the assessment of disorders of consciousness (DoC). Rapidly evolving technologies combined with state-of-the-art data analyses open new horizons to probe brain activity, but selecting appropriate imaging modalities from the plethora of available techniques can be challenging for clinicians. This update reviews selected advances in neuroimaging that demonstrate clinical relevance and translational potential in the assessment of severely brain-injured patients with DoC.

Recent findings

Magnetic resonance imaging and high-density electroencephalography provide measurements of brain connectivity between functional networks, assessments of language function, detection of covert consciousness, and prognostic markers of recovery. Positron emission tomography can identify patients with preserved brain metabolism despite clinical unresponsiveness and can measure glucose consumption rates in targeted brain regions. Transcranial magnetic stimulation and near-infrared spectroscopy are noninvasive and practical tools with promising clinical applications.

Each neuroimaging technique conveys advantages and pitfalls to assess consciousness. We recommend a multimodal approach in which complementary techniques provide diagnostic and prognostic information about brain function. Patients demonstrating neuroimaging evidence of covert consciousness may benefit from early adapted rehabilitation. Translating methodological advances to clinical care will require the implementation of recently published international guidelines and the integration of neuroimaging techniques into patient-centered decision-making algorithms.
Neuralgic amyotrophy
Authors: IJspeert Jos , Janssen Renske M.J. , van Alfen Nens
Published: May 2021

Purpose of review

This review focuses on the current insights and developments in neuralgic amyotrophy (NA), an auto-immune multifocal peripheral nervous system disorder that leaves many patients permanently impaired if not recognized and treated properly.

Recent findings

NA is not as rare as previously thought. The phenotype is broad, and recent nerve imaging developments suggest that NA is the most common cause of acute anterior or posterior interosseous nerve palsy. Phrenic nerve involvement occurs in 8% of all NA patients, often with debilitating consequences. Acute phase treatment of NA with steroids or i.v. immunoglobulin may benefit patients. Long-term consequences are the rule, and persisting symptoms are mainly caused by a combination of decreased endurance in the affected nerves and an altered posture and movement pattern, not by the axonal damage itself. Patients benefit from specific rehabilitation treatment. For nerves that do not recover, surgery may be an option.

NA is not uncommon, and has a long-term impact on patients’ well-being. Early immunomodulating treatment, and identifying phrenic neuropathy or complete nerve paralysis is important for optimal recovery. For persistent symptoms a specific treatment strategy aiming at regaining an energy balance and well-coordinated scapular movement are paramount.
Real-time monitoring of COVID-19 dynamics using automated trend fitting and anomaly detection
Authors: Jombart Thibaut , Ghozzi Stéphane , Schumacher Dirk , Taylor Timothy J. , Leclerc Quentin J. , Jit Mark , Flasche Stefan , Greaves Felix , Ward Tom , Eggo Rosalind M. , Nightingale Emily , Meakin Sophie , Brady Oliver J. ,   Centre for Mathematical Modelling of Infectious Diseases COVID-19 Working Group, Medley Graham F. , Höhle Michael , Edmunds W. John
Published: May 2021

As several countries gradually release social distancing measures, rapid detection of new localized COVID-19 hotspots and subsequent intervention will be key to avoiding large-scale resurgence of transmission. We introduce ASMODEE (automatic selection of models and outlier detection for epidemics), a new tool for detecting sudden changes in COVID-19 incidence. Our approach relies on automatically selecting the best (fitting or predicting) model from a range of user-defined time series models, excluding the most recent data points, to characterize the main trend in an incidence. We then derive prediction intervals and classify data points outside this interval as outliers, which provides an objective criterion for identifying departures from previous trends. We also provide a method for selecting the optimal breakpoints, used to define how many recent data points are to be excluded from the trend fitting procedure. The analysis of simulated COVID-19 outbreaks suggests ASMODEE compares favourably with a state-of-art outbreak-detection algorithm while being simpler and more flexible. As such, our method could be of wider use for infectious disease surveillance. We illustrate ASMODEE using publicly available data of National Health Service (NHS) Pathways reporting potential COVID-19 cases in England at a fine spatial scale, showing that the method would have enabled the early detection of the flare-ups in Leicester and Blackburn with Darwen, two to three weeks before their respective lockdown. ASMODEE is implemented in the free R package
trendbreaker
.

This article is part of the theme issue ‘Modelling that shaped the early COVID-19 pandemic response in the UK’.
Using a household-structured branching process to analyse contact tracing in the SARS-CoV-2 pandemic
Authors: Fyles Martyn , Fearon Elizabeth , Overton Christopher ,   University of Manchester COVID-19 Modelling Group, Wingfield Tom , Medley Graham F. , Hall Ian , Pellis Lorenzo , House Thomas
Published: May 2021

We explore strategies of contact tracing, case isolation and quarantine of exposed contacts to control the SARS-CoV-2 epidemic using a branching process model with household structure. This structure reflects higher transmission risks among household members than among non-household members. We explore strategic implementation choices that make use of household structure, and investigate strategies including two-step tracing, backwards tracing, smartphone tracing and tracing upon symptom report rather than test results. The primary model outcome is the effect of contact tracing, in combination with different levels of physical distancing, on the growth rate of the epidemic. Furthermore, we investigate epidemic extinction times to indicate the time period over which interventions must be sustained. We consider effects of non-uptake of isolation/quarantine, non-adherence, and declining recall of contacts over time. Our results find that, compared to self-isolation of cases without contact tracing, a contact tracing strategy designed to take advantage of household structure allows for some relaxation of physical distancing measures but cannot completely control the epidemic absent of other measures. Even assuming no imported cases and sustainment of moderate physical distancing, testing and tracing efforts, the time to bring the epidemic to extinction could be in the order of months to years.

This article is part of the theme issue ‘Modelling that shaped the early COVID-19 pandemic response in the UK’.
Outbreaks in care homes may lead to substantial disease burden if not mitigated
Authors: Hall Ian , Lewkowicz Hugo , Webb Luke , House Thomas , Pellis Lorenzo , Sedgwick James , Gent Nick ,   on behalf of the University of Manchester COVID-19 Modelling Group and the Public Health England Modelling Team
Published: May 2021

The number of COVID-19 outbreaks reported in UK care homes rose rapidly in early March of 2020. Owing to the increased co-morbidities and therefore worse COVID-19 outcomes for care home residents, it is important that we understand this increase and its future implications. We demonstrate the use of an SIS model where each nursing home is an infective unit capable of either being susceptible to an outbreak (S) or in an active outbreak (I). We use a generalized additive model to approximate the trend in growth rate of outbreaks in care homes and find the fit to be improved in a model where the growth rate is proportional to the number of current care home outbreaks compared with a model with a constant growth rate. Using parameters found from the outbreak-dependent growth rate, we predict a 73% prevalence of outbreaks in UK care homes without intervention as a reasonable worst-case planning assumption.

This article is part of the theme issue ‘Modelling that shaped the early COVID-19 pandemic response in the UK’.