bluuebunny/crossref_metadata_2025 huggingface dataset:
Risk Factors and Prevention of C5 Palsy After Anterior Cervical Decompression and Fusion
Authors: Nakajima Hideaki , Honjoh Kazuya , Watanabe Shuji , Kubota Arisa , Matsumine Akihiko
Published: May 2021

Study Design:

This was a retrospective study.

Objective:

The objective of this study was to review clinical and imaging findings after anterior cervical decompression and fusion, as a basis for prevention of C5 palsy.

Summary of Background Data:

C5 palsy is a common postoperative complication in spine surgery, but the mechanistic basis for this condition is unknown.

Materials and Methods:

The subjects were 239 patients with cervical myelopathy who underwent anterior cervical decompression and fusion including at C4–C5 disk level at our hospital from 2001 to 2018. Twelve of these patients (5.0%) had C5 palsy postoperatively. Clinical features and imaging findings were compared in patients with and without C5 palsy.

Results:

In patients with C5 palsy, the sagittal alignment of the cervical spine was kyphotic, the width of the C5 intervertebral foramen was narrower, and the lateral decompressed line was wider beyond the medial part of the Luschka joint. Age, sex, disease, the number of fused segments, decompression width, and anterior shift of the spinal cord did not differ significantly between patients with and without C5 palsy.

Conclusions:

These results indicate that the pathomechanism of C5 palsy may be dependent on the location of the lateral decompression line, especially in patients with cervical kyphosis and a narrow C5 intervertebral foramen. Excessive lateral decompression beyond the Luchka joint might lead to C5 root kinking between the intervertebral foramen and posterior edge of vertebra. This pathomechanism may be similar in anterior and posterior approaches. To prevent C5 palsy, the medial line of the Luschka joint should be confirmed intraoperatively and decompression should be performed within the Luschka joints. Alternatively, medial foraminotomy should be used in cases needing wide decompression, such as those with massive ossification of the posterior longitudinal ligament, lateral osteophytes, and symptomatic foraminal stenosis.

Level of Evidence:

Level III.
Transfer of Motor Fascicle From the Median to the Axillary Nerve for Upper Brachial Plexus Injury: A Surgical Technique and Case Report
Authors: Vergara-Amador Enrique , López-Rincón Laura
Published: May 2021

Upper brachial plexus injury or isolated lesions of the axillary nerve (AN) compromise shoulder functionality significantly. Different surgical techniques have been described for selective reconstruction of the AN, with good results especially in association with repair of the suprascapular nerve. The objective of this study is to describe the transfer of motor fascicles of the median nerve to the AN by an axillary approach in cadavers and the clinical results in 2 patients. Dissections were performed on 5 cadavers, followed by identification and dissection of the AN and its divisions before entering the quadrangular space. We standardized the surgical technique in which the median nerve was first identified and then an intrafascicular dissection was performed. Then we harvested a fascicle and transferred it to the anterolateral branch of the AN. Two patients underwent an operation; at 2 years of follow-up, average abduction of 125 degrees and external rotation of 95 degrees were observed. In conclusion, the transfer of motor fascicles of the median nerve to the AN by an axillary approach could be an alternative technique for the deltoid reinnervation in upper brachial plexus injury. Some advantages are the proximity of the donor nerve to the receptor nerve and the low morbidity of the target muscles of the donor nerve. Studies with a larger number of patients are required to establish its effectiveness compared with other techniques already described.
The Agonist-antagonist Myoneural Interface
Authors: Herr Hugh , Carty Matthew J.
Published: May 2021

Scientist and technologist have long sought to advance limb prostheses that connect directly to the peripheral nervous system, enabling a person with amputation to volitionally control synthetic actuators that move, stiffen and power the prosthesis, as well as to experience natural afferent sensations from the prosthesis. Recently, the agonist-antagonist myoneural interface (AMI) was developed, a mechanoneural transduction architecture and neural interface system designed to provide persons with amputation improved muscle-tendon proprioception and neuroprosthetic control. In this paper, we provide an overview of the AMI, including its conceptual framing and preclinical science, surgical techniques for its construction, and clinical efficacy related to pain mitigation, phantom limb range of motion, fascicle dynamics, central brain proprioceptive sensorimotor preservation, and prosthetic controllability. Following this broad overview, we end with a discussion of current limitations of the AMI and potential resolutions to such challenges.
Do the 2013 United States Preventive Services Task Force guidelines for lung cancer screening fail high-risk African American smokers? An institutional retrospective observational cohort study
Authors: Thurlapati Aswani , Velez-Martinez Carol S. , Hirani Samina , Abad Jade , Shi Runhua , Beedupalli Kavitha , Mansour Richard P.
Published: May 2021

Background

Lung cancer cause nearly 1.76 million deaths worldwide in 2018. In 2011, the National-Lung-Cancer-Screening-Trial showed 20% relative risk reduction with LDCT and subsequently led to the current USPSTF screening guidelines. However, the predominant focus on elderly, Caucasian questions its generalizability to communities with young, African Americans such as our institution. Hence, the objective of our study is to investigate the need to modify the current screening guidelines at our institution by assessing the applicability of newer individual risk-based prediction models for LDCT screening.

Methods

This is a retrospective observational cohort study of newly diagnosed lung cancer patients at LSU Health Sciences Center Shreveport from 2011 to 2015. One-third of the patients did not meet the current USPSTF screening guidelines. We categorized them into high-risk (groups1 and 2), moderate-risk, and low-risk according to 2018 NCCN Lung Cancer Screening Guidelines Version 1.2020. The high-risk groups were differentiated using the Tammemagi lung cancer risk calculator.

Results

Among those who did not meet the screening guidelines, nearly 50% were African American, 95% with known smoking history, and 80% diagnosed at advanced stage at the time of diagnosis. After employing the Tammemagi Risk based calculator, 12.5% were categorized into high-risk group 2, who are also eligible for annual LDCT.

Conclusion

The current USPSTF guidelines have failed in our population consisting of young African American smokers, questioning the health disparity in medicine. By employing individual risk-based prediction models, we could potentially identify tailored high-risk populations leading to appropriate use of LDCT screening.
Risk factors for cardiovascular mortality and melanoma-specific mortality among patients with melanoma: a SEER based study
Authors: Elshanbary Alaa Ahmed , Zaazouee Mohamed Sayed , Abdelmonem Mohamed , Mohammed Yasmine Adel , Abdel-Aziz Walid
Published: May 2021

Objective

This study aims to identify the risk factors for cardiovascular mortality in melanoma patients.

Methods

Data of melanoma patients were obtained from the Surveillance, Epidemiology, and End Results database. We used Person’s chi-square test to assess the relationships between categorical variables. We used Kaplan–Meier test in the univariate analysis and Cox regression test for the multivariate analysis. Analyses were conducted using the SPSS software.

Results

We analyzed data of 194 503 melanoma patients. Among them, 28 818 (14.8 %) died due to cardiovascular diseases. Cardiovascular-specific survival was higher in younger patients, women, married, localized disease, superficial spreading melanoma and in patients who had surgery. It was lower in patients who received chemotherapy or radiotherapy. The multivariate analysis revealed a higher risk of cardiovascular mortality in patients aged 50–64 years [hazard ratio (HR), 7.297; 95% confidence interval (CI), 6.68–7.97], patients aged ≥65 years (HR, 43.309; 95% CI, 39.706–47.240), men (HR, 1.535; 95% CI, 1.475–1.597), Blacks (HR, 1.29; 95% CI, 1.044–1.594), separated (HR, 1.286; 95% CI, 1.058–1.562), widowed (HR, 1.829; 95% CI, 1.706–1.961), patients with no or unknown history of chemotherapy (HR, 1.302; 95% CI, 1.071–1.583) or radiotherapy (HR, 1.477; 95% CI, 1.217–1.793) and patients with no surgery (HR, 1.468; 95% CI, 1.264–1.706).

Conclusions

In patients with melanoma, the risk of cardiovascular death is higher in older patients, men, Blacks, separated, widowed and patients with nodular or lentigo maligna melanoma. The risk is lower in married, patients with superficial spreading or acral lentiginous melanoma, and patients who had chemotherapy, radiotherapy or surgery.
Equal prevalence of severe cervical dysplasia by HPV self-sampling and by midwife-collected samples for primary HPV screening: a randomised controlled trial
Authors: Hellsten Caroline , Ernstson Avalon , Bodelsson Gunilla , Forslund Ola , Borgfeldt Christer
Published: May 2021

Objectives

HPV self-sampling is an option for cervical screening. The aim of this randomised study was to investigate the compliance, prevalence of HPV, and prevalence of severe dysplasia in a vaginal self-sampling group in comparison to cervical samples collected by midwives (control arm). The hypothesis was that there would be no difference between vaginal self-sampling and cervical sampling to find high-grade cervical dysplasia or cancer.

Methods

Vaginal HPV self-sampling kits were sent by regular mail to 14 765 randomly selected women aged 30–64 years old in the screening programme. HPV-positive women were invited for a follow-up examination by their midwife in which they provided a cervical sample for cytological and HPV co-testing. The control arm consisted of 14 839 women who met the same inclusion criteria and were invited to have cervical sampling by midwives for primary HPV screening. All HPV samples were analysed by the Aptima HPV assay (Hologic Inc.).

Main results

The participation rate was 33.5% in the self-sampling arm and 47.5% in the cervical sampling arm, (P < 0.0001). HPV was detected in 17.1% (95% confidence interval (CI), 16.1–18.23%) in the self-sampling arm and 4.5% (95% CI, 4.0–5.0%) in the cervical sampling arm. Histological, severe dysplasia was observed among 0.48% (95% CI, 0.3–0.72%) and 0.47% (95% CI, 0.3–0.66%) of the self-sampling and the cervical sampling groups, respectively.

Conclusion

The self-sampling approach detects a similar proportion of severe dysplasia as regular screening. Thus, our study indicates that self-sampling could replace primary HPV screening of cervical samples.
A Unified Approach to Quality From the Bedside to C-Suite and Back Again
Authors: DiCuccio Margaret Hardt , Cohen Jeffrey , Rupert Duke , Jaffee Don
Published: May 2021

The cost of a prolonged critical care admission is often the driver of the high cost of care. At a time when the health care system in the United States is absorbing an increasing percentage of the gross domestic product, an understanding of the value equation is essential. The pressure to provide high-quality care at a cost that the nation can shoulder unifies the bedside nurse and the C-suite to a common goal. The president, chief operating officer, and chief financial officer of a large urban teaching hospital were interviewed to provide some insight into how C-suite members view the value equation and the role of critical care nurses in achieving success.
Histologic Patterns of Cutaneous Metastases of Breast Carcinoma: A Clinicopathologic Study of 232 Cases
Authors: Ronen Shira , Suster David , Chen Wei-Shen , Ronen Natali , Arudra Sri Krishna C. , Trinidad Celestine , Ivan Doina , Prieto Victor G. , Suster Saul
Published: May 2021

Cutaneous metastasis may be the initial sign of internal malignancy but more often represents a late manifestation of widely disseminated disease. Breast carcinoma is the most common malignancy to metastasize to the skin. Although several studies have detailed the histopathologic patterns of cutaneous metastasis from internal malignancies, very little has been published regarding metastases of breast carcinoma to the skin. Furthermore, the histopathologic and clinical features observed in the cases of breast carcinoma with local skin involvement as opposed to cases exhibiting distant cutaneous metastases have not been adequately investigated. We have reviewed 232 cases of breast carcinoma with cutaneous metastases from 2 large institutions. All cases of carcinoma of the breast with involvement of the skin of the anterior chest wall were compared with those with distant cutaneous metastases. Two hundred thirty-two cases in 199 patients were included, of which 126 had skin involvement exclusively involving the ipsilateral anterior chest, and 106 had biopsy-proven distant cutaneous metastases. Twelve patients had both local and distal spread. Distant cutaneous metastases showed a predilection for the contralateral anterior chest wall area, followed by the head and neck, back, and abdomen. Histologically, most of the tumors presented in this series showed features of infiltrating ductal carcinoma. In both ipsilateral and distant metastases, the tumors demonstrated little change in histologic features from the primary lesion; however, the distant metastases showed a tendency to display more poorly differentiated features. The mean patient survival when cutaneous involvement was localized to the skin of the anterior chest wall was 23 months as compared with 20.6 months when distant sites were affected. A comparison of the clinicopathologic features of the patients presented in this series suggests that alternate biological mechanisms may apply for local and distant skin metastases from breast carcinoma.
White blood cell count and clinical outcomes after left main coronary artery revascularization: insights from the EXCEL trial
Authors: Claessen Bimmer E. , Ben-Yehuda Ori , Mehran Roxana , Sorrentino Sabato , Guedeney Paul , Chen Shmuel , Dressler Ovidiu , Kini Annapoorna S. , Sharma Samin K. , Mansour Samer , Noiseux Nicolas , Li Ditian , Kappetein Arie Pieter , Sabik Joseph F. , Serruys Patrick W. , Stone Gregg W.
Published: May 2021

Background

Prior studies have reported an association between elevated white blood cell count (WBCc) and worse clinical outcomes after coronary artery bypass grafting (CABG) and percutaneous coronary intervention (PCI). We assessed the prognostic impact of WBCc in patients undergoing revascularization for left main coronary artery disease (LMCAD).

Methods

In Evaluation of XIENCE Versus Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularization (EXCEL), 1905 patients with LMCAD and low or intermediate SYNTAX scores were randomized to PCI with everolimus-eluting stents versus CABG. The 1895 patients with baseline WBCc available were grouped in tertiles of WBCc (mean 5.6 ± 0.8, 7.5 ± 0.5, and 10.1 ± 1.6 × 109/L).

Results

Five-year rates of the primary endpoint (death, myocardial infarction or stroke) were similar across increasing WBCc tertiles (21.2, 18.9, and 21.6%; P = 0.46). Individual components of the primary endpoint, Bleeding Academic Research Consortium (BARC) 3–5 bleeding, stent thrombosis or graft occlusion and ischemia-driven revascularization were all similar across WBCc tertiles. By multivariable analysis, WBCc as a continuous variable was not an independent predictor of adverse events (hazard radio per 1 × 109/L: 1.02; 95% CI, 0.97–1.08; P = 0.43). Results were consistent in the PCI and CABG arms individually.

Conclusion

There was no association between baseline WBCc and 30-day or 5-year clinical outcomes after PCI or CABG. The absence of a clear incremental increase in events with increasing WBCc in the current analysis indicates that WBCc should not routinely be used as a prognostic marker or to guide revascularization decisions in patients with LMCAD.
Impact of renin-angiotensin system inhibitors after revascularization of patients with left main coronary artery disease
Authors: Chen Shmuel , Redfors Björn , Serruys Patrick W. , Pieter Kappetein Arie , Crowley Aaron , Ben-Yehuda Ori , Srdanovic Iva , Lembo Nicholas J. , Brown W. Morris , Sabik Joseph F. , Stone Gregg W.
Published: May 2021

Background

There is a paucity of data regarding the effect of inhibition of the renin-angiotensin system on outcomes after percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG). We sought to examine long-term outcomes of patients with left main coronary disease (LMCAD) randomized to PCI with fluoropolymer-based cobalt–chromium everolimus-eluting stents or CABG according to treatment at discharge with angiotensin-converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB) in the large-scale, multicenter, randomized EXCEL trial.

Methods

EXCEL randomized 1905 patients with LMCAD of low and intermediate anatomical complexity (visually-assessed SYNTAX score ≤32) to PCI (n = 948) versus CABG (n = 957). Patients were categorized according to whether they were treated with ACEI/ARB at discharge; their outcomes from discharge to 5 years were examined using multivariable logistic regression with an offset for follow-up time.

Results

Among 1775 patients discharged alive with known ACEI/ARB treatment status, 896 (50.5%) were treated with one of these agents. Among those treated with ACEI/ARB, the 5-year rate of all-cause death was similar after PCI or CABG (10.7% versus 9.8% respectively, adjOR, 0.94; 95% CI, 0.56–1.57) in contrast to patients not treated with ACEI/ARB (15.0% versus 7.8%, respectively, adjOR, 2.20; 95% CI, 1.32–3.67) (P
interaction = 0.02). Significant interactions between treatment arm (PCI versus CABG) and ACEI/ARB treatment status were also found for cardiovascular death (P
interaction = 0.03), ischemia-driven revascularization (P
interaction = 0.03), target vessel revascularization (P
interaction = 0.007) and target vessel failure (P
interaction = 0.0009).

Conclusion

In the EXCEL trial, the postdischarge rates of death and revascularization after 5 years were similar after PCI and CABG in patients with LMCAD treated with ACEI/ARB at discharge. In contrast, event rates were higher after PCI versus CABG in those not so treated.
Predictive value of spiral shape in coronary plaque progression: an intraindividual comparative study
Authors: Wang Zhao-qian , Yuan You-sheng , Wang Hao , Dou Ya-na , Jia Chong-fu
Published: May 2021

Objective

We conducted a pilot study to explore the value of spiral-shaped sign of plaque from coronary computed tomographic angiography (CCTA) in predicting plaque progression by intraindividual comparison.

Methods

A total of 30 patients with a total of 60 plaques who received serial CCTA were retrospectively included and intraindividual compared. The spiral shape was defined as plaques coursing along the long axis of a coronary artery and encircling it at an angle of ≥ 180 degrees. The high-risk and other plaque signs were recorded.

Results

On baseline CCTA, the spiral shape (P < 0.01) and length (P < 0.05) of plaques were more frequently seen in the progression group than in the nonprogression group; however, there was no difference between two groups in terms of high-risk plaque signs. In the progression group, plaque length, volume, and napkin-ring sign on follow-up CCTA were significantly greater than at baseline (P < 0.05). In the nonprogression group, there were fewer low-attenuation and positive remodeling plaques on follow-up CCTA than at baseline (P < 0.05). The spiral shape (standardized β = –4.55; P < 0.01) was an independent risk factor for plaque progression. There were 24 spiral plaques in the progression group, of which 16 (66.7%) had progression below the twist point of the spiral shape.

Conclusions

The baseline spiral shape is more frequently found in those lesions that progress than in those that do not in patients with multiple coronary lesions, and the spiral shape is an independent predictor of which plaques will progress.
Advanced glycation endproducts and bone quality: practical implications for people with type 2 diabetes
Authors: Moseley Kendall F. , Du Zexu , Sacher Sara E. , Ferguson Virginia L. , Donnelly Eve
Published: May 2021

Purpose of review

Individuals with type 2 diabetes (T2D) are at increased risk of fracture, often despite normal bone density. This observation suggests deficits in bone quality in the setting of abnormal glucose homeostasis. The goal of this article is to review recent developments in our understanding of how advanced glycation end products (AGEs) are incorporated into the skeleton with resultant deleterious effects on bone health and structural integrity in patients with T2D.

Recent findings

The adverse effects of skeletal AGE accumulation on bone remodeling and the ability of the bone to deform and absorb energy prior to fracture have been demonstrated both at the bench as well as in small human studies; however, questions remain as to how these findings might be better explored in large, population-based investigations.

Hyperglycemia drives systemic, circulating AGE formation with subsequent accumulation in the bone tissue. In those with T2D, studies suggest that AGEs diminish fracture resistance, though larger clinical studies are needed to better define the direct role of longstanding AGE accumulation on bone strength in humans as well as to motivate potential interventions to reverse or disrupt skeletal AGE deposition with the goal of fracture prevention.
Single-use duodenoscopes: where are we and where are we going?
Authors: Peter Shajan , Bang Ji Young , Varadarajulu Shyam
Published: May 2021

Purpose of review

Given the growing concerns about infection transmission from use of contaminated reusable duodenoscopes, technological advancements have been made that vary from modifications of existing designs to development of single-use devices.

Recent findings

To circumvent mechanical limitations that preclude access to critical areas of a duodenoscope to perform thorough cleaning and disinfection, single-use disposable duodenoscopes have been developed. A thorough assessment of this technology is limited by the minimal published data that is currently available. This opinion assesses the current technical functionality of these devices, potential for further improvements, implications for healthcare economics and the future of gastrointestinal endoscopy.

Currently available data suggest that majority of endoscopic retrograde cholangiopancreatography procedures can be safely performed using single-use duodenoscopes. The ability to improve technical functionality, incorporate futuristic technology and secure financial reimbursement from insurance carriers will largely define the future prospects of this recent innovation.
Role of VLDL receptor in atherogenesis
Authors: Takahashi Sadao
Published: May 2021

Purpose of review

My group previously discovered and characterized the rabbit and human VLDL receptors. For more than 30 years, I have focused on research regarding the functions of VLDL receptors in the fields of lipoprotein metabolism and atherogenesis. In this review, I introduce the roles of VLDL receptors in lipoprotein metabolism under physiological conditions and in atherogenesis under nonphysiological conditions.

Recent findings

I propose that the VLDL receptor plays key roles in the metabolism of postprandial remnant lipoproteins in concert with lipoprotein lipase (LPL). Furthermore, I propound a new mechanism for macrophage foam cell formation via VLDL receptors by remnant lipoproteins and lipoprotein(a) [Lp(a)] in addition to scavenger receptor pathways.

The VLDL receptor is a so-called macrophage β-VLDL receptor, which is involved in macrophage foam cell formation by remnant lipoproteins. Furthermore, Lp(a) is a VLDL receptor ligand and is directly taken up through macrophage VLDL receptors for macrophage foam cell formation. Additionally, the roles of VLDL receptors in atherogenesis are canvassed.

Supplementary video abstract

http://links.lww.com/COL/A21
The Fuelbox “Young Next of Kin”—A Mixed-Methods Study on the Development and Piloting of a Communication Tool for Adolescents Coping With Parental Cancer or Death
Authors: Hauken May Aasebø , Farbrot Inger Marie
Published: May 2021

Background

Adolescents’ ability to cope with parental cancer and death is largely dependent on information and open communication, but parents and professionals often feel uncertain in such circumstances.

Objectives

To develop and pilot a communication tool to enhance communication with adolescents living with or having lost a parent with cancer.

Methods

A Fuelbox was developed in a 4-phased process including adolescents and professionals and piloted by 51 participants (adolescents, parents, and professionals) over 4 months. Using a mixed-methods study with a convergent design, data were collected via a questionnaire and interviews and were then merged.

Results

The final “Young Next of Kin” Fuelbox consisted of 8 topics and 176 questions. Participants used the Fuelbox in different contexts, utilizing a variety of approaches. The participants found that it covered significant topics and questions important to adolescents’ situation. The Fuelbox was considered a very useful and beneficial tool to promote communication with adolescents, given that users maintain awareness of voluntary participation, confidentiality, preparedness, time, and safe frames.

Conclusion

The Fuelbox “Young Next of Kin” seems to be a flexible and accessible communication tool in private and professional settings to enhance communication with adolescents living with or having lost a parent with cancer. As the Fuelbox is diagnosis-neutral in nature, it may be transferable to other populations and settings.

Implications for Clinical Practice

The Fuelbox is a flexible, accessible, and useful tool for communication between adolescents and parents, and adolescents and healthcare professionals in specialist and primary healthcare settings.
The Global Pandemic
Authors: Boston-Fleischhauer Carol
Published: May 2021

The COVID pandemic generated unparalleled operational disruption. C-suites and chief nurse executives responded to create capacity and clinical readiness despite enormous uncertainty. Innovations were put in place to combat the care crisis; however, is there merit in continuing these innovations as the pandemic subsides? Examining highly impactful operational innovations that were rapidly implemented during the pandemic should be prioritized as organizations seek to establish their new normal.
Physical Examination—Indicated Cerclage in Twin Pregnancy: A Randomized Controlled Trial
Authors: Roman Amanda , Zork Noelia , Haeri Sina , Schoen Corina N. , Saccone Gabriele , Colihan Sarah , Zelig Craig , Gimovsky Alexis C. , Seligman Neil S. , Zullo Fulvio , Berghella Vincenzo
Published: May 2021

(Abstracted from Am J Obstet Gynecol 2020;223:902.e1–902.e11)

Twin pregnancies in the United States represent a small proportion of births each year, but they are associated with increased risks of preterm birth (PTB), low birthweight, and perinatal mortality. In the setting of cervical dilation in the second trimester, the risks for complications in a twin pregnancy are even higher.
Intrapatient Tumor Heterogeneity in IHC Interpretation Using PD-L1 IHC 22C3 pharmDx
Authors: Kalpakoff Megan , Hund Stephanie , Musser Jeanette , Roach Charlotte , Apostolaki Angeliki , Vilardo Monika , Peltz Lindsay , Watts Brittany , LaPlaca Chris , Tabuena-Frolli Siena , DiMaio Michael A. , Welcher Rosanne , Kulangara Karina
Published: May 2021

Tumor heterogeneity may impact immunohistochemical (IHC) interpretation, thus potentially affecting decision making by treating oncologists for cancer patient management. Programmed cell death ligand-1 (PD-L1) IHC 22C3 pharmDx is a companion diagnostic used as an aid in identifying patient eligibility for treatment with pembrolizumab (KEYTRUDA). This study aims to investigate tumor heterogeneity impact on IHC staining when evaluating PD-L1 expression using PD-L1 IHC 22C3 pharmDx. The effect of tumor heterogeneity was evaluated based on the PD-L1 diagnostic status of PD-L1 IHC 22C3 pharmDx stained tumor tissue sections at relevant diagnostic cutoffs for non–small cell lung carcinoma, gastric or gastroesophageal junction adenocarcinoma, urothelial carcinoma, head and neck squamous cell carcinoma, esophageal cancer and triple negative breast cancer. Overall agreement for the PD-L1 diagnostic status was assessed for each tumor type within a given specimen block (Intra-Block), between specimen blocks from the same surgical resection (Intra-Case), and between intrapatient primary and metastatic specimens. Intrablock and intracase point estimates were above 75%, and primary versus metastatic point estimates were above 50%. The results suggest that PD-L1 expression is consistent across cut sections through a minimum of 150 µm within a tissue block and between blocks from the same surgical resection and is significantly maintained across primary and metastatic blocks from the same patient despite changes to the tissue microenvironment. These data provide confidence for histopathologists and oncologists that evaluation of PD-L1 expression at clinically relevant cutoffs is reproducible among different assessments (or samplings) of a single tumor specimen.
Preliminary Computed Tomography Radiomics Model for Predicting Pretreatment CD8+ T-Cell Infiltration Status for Primary Head and Neck Squamous Cell Carcinoma
Authors: Wang Colin Y. , Ginat Daniel Thomas
Published: May 2021

Purpose

Immunotherapy has emerged as a treatment option for head and neck squamous cell carcinoma (HNSCC), with tumor response being linked to the CD8+ T-cell inflammation. The purpose of this study is to assess whether computed tomography (CT) radiomic analysis can predict CD8+ T-cell enrichment in HNSCC primary tumors.

Methods

This retrospective study included 71 patients from a head and neck cancer genomics cohort with CD8+ T-cell enrichment status. Pretreatment contrast-enhanced neck CT scans were retrospectively reviewed using 3D Slicer for primary lesion segmentation.

The SlicerRadiomics extension was used to extract 107 radiomic features. Ridge regression and lasso regression were applied for feature selection and model construction.

Results

Lasso regression defined Coarseness as the most important variable, followed by SmallDependenceEmphasis, SmallAreaLowGrayLevelEmphasis, Contrast.1, and Correlation.

Ridge regression defined Coarseness as the most important variable, followed by SmallDependenceLowGrayLevelEmphasis, Contrast.1, DependenceNonUniformityNormalized, and Idmn. These variables identified by lasso and ridge regressions were used to create a combined logistic regression model. The area under the curve (AUC) for the lasso-generated model was 0.786 (95% confidence interval [CI], 0.532–1.000), and the AUC for the ridge-generated model was 0.786 (95% CI, 0.544–1.000). Combining the radiomic variables identified by lasso and ridge regressions with clinical characteristics including alcohol use, tobacco use, anatomic site, and initial T stage produced a model with an AUC of 0.898 (95% CI, 0.731–1.000).

Conclusions

T-cell inflammation status of HNSCC primary tumors can be predicted using radiomic analysis of CT imaging and thereby help identify patients who would respond well to immunotherapy.
Detection of Antibodies Against Human Leukocyte Antigen Class II in the Sera of Patients Receiving Intravenous Immunoglobulin
Authors: Takamatsu Hiroyuki , Yamada Shinya , Tsuji Noriaki , Nakagawa Noriharu , Matsuura Erika , Kasada Atsuo , Sato Keijiro , Hosokawa Kohei , Iwaki Noriko , Arahata Masahisa , Tanaka Hidenori , Nakao Shinji
Published: May 2021

Background.

IVIG is occasionally used for preventing and treating severe infections of patients who are to undergo transplantation. Administration of IVIG, which includes high-titer antibodies (Abs) against HLA class I and II, might have a substantial influence on the HLA Ab test results of these patients. However, this issue has remained unreported.

Methods.

Anti-HLA Ab titers were determined in 4 types of IVIG preparations, fresh frozen plasma, and the sera of 11 patients with hematological diseases before and after IVIG administration.

Results.

Although anti-HLA Abs were not detected in any of the fresh frozen plasma products, various anti-HLA class I and II Abs were detected in all 4 IVIG preparations. Six out of 11 patients who had received IVIG showed a low titer of anti-HLA class II Abs, which were not detected before IVIG administration. Conversely, no anti-HLA class I Abs were detected in any of the 11 patients. Furthermore, all 4 (100%) patients who were positive for anti-HLA class II Abs initially and were assessable became negative for anti-HLA Abs after the discontinuation of IVIG treatment (median, d 79; range, d 22–192).

Conclusions.

IVIG preparations consist of high-titer anti-HLA class I and II Abs, but the latter can be transiently detected in the sera of patients who had received IVIG. When these patients are screened for the presence of donor-specific Abs, some may be incorrectly deemed positive for HLA class II Abs. Thus, caution is necessary when only donor-specific Abs specific to class II HLAs are detected in patients.
Autoimmune movement disorders with neuronal antibodies – an update
Authors: Balint Bettina , Bhatia Kailash P.
Published: May 2021

Purpose of review

The rapid developments in neuroimmunology reflect also on the field of movement disorders, where there is an ever expanding spectrum of new antibodies. This review focuses on the new neuronal antibodies, their clinical spectrum and recent pathophysiological insights. It gives an update on previous work about neuronal antibody-related movement disorders.

Recent findings

Phosphodiesterase 10A antibodies are a new marker of paraneoplastic chorea. Seizure-related 6 homolog like 2 antibodies are a differential diagnosis in atypical parkinsonism with cerebellar ataxia and cognitive impairment. mGluR5-antibodies cause various hyperkinetic movement disorders with Ophelia syndrome. Most new antibodies were described in the context of cerebellar ataxia: Kelch-like protein 11 antibodies are a comparatively frequent marker of paraneoplastic cerebellar ataxia with germ cell tumours. Nonparaneoplastic cerebellar ataxia occurs with Septin-5 and neurochondrin antibodies. Studies into the mechanisms of neuronal surface antibodies have shown that there is much pathophysiological heterogeneity, ranging from immediate antagonistic effect to induction of neurodegeneration after weeks.

The new markers of autoimmune movement disorders are key to identify those patients that may benefit from immunotherapy, and tumour therapy, where appropriate. Insights into the underlying pathophysiology might guide treatment decisions and help tailoring more targeted approaches in the future.
Manifestation of Hippocampal Interictal Discharges on Clinical Scalp EEG Recordings
Authors: Lee Somin , Wu Shasha , Tao James X. , Rose Sandra , Warnke Peter C. , Issa Naoum P. , van Drongelen Wim
Published: May 2021

Purpose:

Epileptiform activity limited to deep sources such as the hippocampus currently lacks reliable scalp correlates. Recent studies, however, have found that a subset of hippocampal interictal discharges may be associated with visible scalp signals, suggesting that some types of hippocampal activity may be monitored noninvasively. The purpose of this study is to characterize the relationship between these scalp waveforms and the underlying intracranial activity.

Methods:

Paired intracranial and scalp EEG recordings obtained from 16 patients were used to identify hippocampal interictal discharges. Discharges were grouped by waveform shape, and spike-triggered averages of the intracranial and scalp signals were calculated for each group. Cross-correlation of intracranial and scalp spike-triggered averages was used to determine their temporal relationship, and topographic maps of the scalp were generated for each group.

Results:

Cross-correlation of intracranial and scalp correlates resulted in two classes of scalp waveforms—those with and without time delays from the associated hippocampal discharges. Scalp signals with no delay showed topographies with a broad field with higher amplitudes on the side ipsilateral to the discharges and a left–right flip in polarity—observations consistent with the volume conduction of a single unilateral deep source. In contrast, scalp correlates with time lags showed rotational dynamics, suggesting synaptic propagation mechanisms.

Conclusions:

The temporal relationship between the intracranial and scalp signals suggests that both volume conduction and synaptic propagation contribute to these scalp manifestations. Furthermore, the topographic evolution of these scalp waveforms may be used to distinguish spikes that are limited to the hippocampus from those that travel to or engage other brain areas.
Enhancement of damaged-image prediction through Cahn–Hilliard image inpainting
Authors: Carrillo José A. , Kalliadasis Serafim , Liang Fuyue , Perez Sergio P.
Published: May 2021

We assess the benefit of including an image inpainting filter before passing damaged images into a classification neural network. We employ an appropriately modified Cahn–Hilliard equation as an image inpainting filter which is solved numerically with a finite-volume scheme exhibiting reduced computational cost and the properties of energy stability and boundedness. The benchmark dataset employed is Modified National Institute of Standards and Technology (MNIST) dataset, which consists of binary images of handwritten digits and is a standard dataset to validate image-processing methodologies. We train a neural network based on dense layers with MNIST, and subsequently we contaminate the test set with damages of different types and intensities. We then compare the prediction accuracy of the neural network with and without applying the Cahn–Hilliard filter to the damaged images test. Our results quantify the significant improvement of damaged-image prediction by applying the Cahn–Hilliard filter, which for specific damages can increase up to 50% and is advantageous for low to moderate damage.
The expanding field of non-canonical RNA capping: new enzymes and mechanisms
Authors: Wiedermannová Jana , Julius Christina , Yuzenkova Yulia
Published: May 2021

Recent years witnessed the discovery of ubiquitous and diverse 5′-end RNA cap-like modifications in prokaryotes as well as in eukaryotes. These non-canonical caps include metabolic cofactors, such as NAD+/NADH, FAD, cell wall precursors UDP-GlcNAc, alarmones, e.g. dinucleotides polyphosphates, ADP-ribose and potentially other nucleoside derivatives. They are installed at the 5′ position of RNA via template-dependent incorporation of nucleotide analogues as an initiation substrate by RNA polymerases. However, the discovery of NAD-capped processed RNAs in human cells suggests the existence of alternative post-transcriptional NC capping pathways. In this review, we compiled growing evidence for a number of these other mechanisms which produce various non-canonically capped RNAs and a growing repertoire of capping small molecules. Enzymes shown to be involved are ADP-ribose polymerases, glycohydrolases and tRNA synthetases, and may potentially include RNA 3′-phosphate cyclases, tRNA guanylyl transferases, RNA ligases and ribozymes. An emerging rich variety of capping molecules and enzymes suggests an unrecognized level of complexity of RNA metabolism.
Public attitudes to COVID-19 vaccines: A qualitative study
Authors: Williams Simon N , Dienes Kimberly
Published: May 2021

OBJECTIVE

To explore public attitudes to COVID-19 vaccines in the UK, focused on intentions and decisions around taking vaccines, views on ‘vaccine passports’, and experiences and perspectives on post-vaccination behavior.

DESIGN

Qualitative study consisting of 6 online focus groups conducted between 15th March – 22nd April 2021.

SETTING

Online video conferencing

PARTICIPANTS

29 adult UK-based participants

RESULTS

Three main groups regarding participants’ decision or intention to receive a COVID-19 vaccine were identified: (1) Accepters, (2) Delayers and (3) Refusers. Two reasons for vaccine delay were identified: delay due to a perceived need more information and delay until vaccine was “required” in the future. Three main facilitators (Vaccination as a social norm; Vaccination as a necessity; Trust in science) and six barriers (Preference for “natural immunity”; Concerns over possible side effects; Distrust in government; Perceived lack of information; Conspiracy theories; “Covid echo chambers”) to vaccine uptake were identified. For some delayers, vaccine passports were perceived to be a reason why they would get vaccinated in the future. However, vaccine passports were controversial, and were framed in three main ways: as “a necessary evil”; as “Orwellian”; and as a “human rights problem”. Participants generally felt that receiving a vaccine was not changing the extent to which people were adhering to COVID-19 measures.

CONCLUSIONS

Overall, positive sentiment toward vaccines was high. However, there remains a number of potential barriers which might be leading to vaccine delay in some. ‘Vaccine delay’ might be a more useful and precise construct than vaccine hesitancy in explaining why some may initially ignore or be uncertain about vaccination invitations. Vaccine passports may increase or ‘nudge’ uptake in some delayers but remain controversial. Earlier concerns that vaccination might reduce adherence to social distancing measures are not borne out in our data, with most people reporting ongoing adherence and caution.
Evaluation on the Effectiveness on the Implementation of WHO-CST Programme in Hong Kong: A RCT Protocol
Authors: Wong Paul Wai-Ching , Chow Siu-Lun
Published: May 2021

Developmental delays/disorders in young children are identified as a public health priority. WHO and Autism Speaks co-designed a training programme titled “WHO-Caregiver Skills Training” (WHO-CST) which aims at providing training for caregivers whose children are with possible symptoms of Autism spectrum disorder (ASD) symptoms and pervasive developmental disorders (PDD), so that they can learn better strategies on managing the daily lives of their children and foster better communication between the parent-children dyad. The WHO-CST programme is currently implemented in more than 30 regions worldwide and it started in Hong Kong from 2018. As the programme is newly developed, only a few studies tried to evaluate the effectiveness of the programme in qualitative approaches, or in quantitative approach with relatively small sample (e.g. n < 10). In the present study, our team, who is responsible for the implementation and evaluation of the WHO-CST programme in Hong Kong, attempt to assess the effectiveness of the training in WHO-CST under a randomized controlled trial (RCT) design with about 120 eligible caregivers who will be randomly assigned in experimental and control groups. Our measurement will include the Joint Engagement Rating Inventory (JERI) developed by experts in WHO to gauge how parents engage their children in a 10-minute video recording their dyadic interaction and behaviors in a defined play setting. A set of other measurements on the caregiver’s experience of using intervention skills and their enhancement of knowledges will also be measured. We hypothesize that caregivers in treatment group will have better growth in scores of both JERI and measurements of other outcome than the wait-list control group’s after the 12-week WHO-CST training, and also persistence of skill and knowledge level should also be found after a 30-day follow-up test.
miR-2 contributes to WSSV infection by targeting Caspase 2 in mud crab (Scylla paramamosain)
Authors: Gong Yi , Chen Jiao , Cui Yalei , Li Shengkang
Published: May 2021

As we known, Caspase 2 is widely studied for its apoptosis regulatory function in mammals. However, despite the fundamental role of apoptosis during the anti-viral immune response, the relationship between Caspase 2 and virus infection has not been extensively explored in invertebrates, whether miRNAs are involved in this process also remains unclear. To address this issue, the miRNA-mediated regulation of Caspase 2 in mud crab Scylla paramamosain was characterized in this study. The results suggested that Sp-Caspase 2 could suppress white spot syndrome virus (WSSV) infection via apoptosis induction. The further data showed that Caspase 2 was directly targeted by miR-2 in mud crab. Silencing or overexpression of miR-2 could affect apoptosis and WSSV replication through regulating the expression level of Caspase 2. Taken together, all these results demonstrated the crucial role of miR-2-Caspase 2 pathway in the innate immunity of mud crab and revealed a novel mechanism during anti-viral immune response in marine invertebrates.
The impact of leadership on the nursing workforce during the COVID-10 pandemic
Authors: Phillips Natasha , Hughes Luke , Vindrola-Padros Cecilia , Petrella Anika , Fern Lorna A , Panel-Coates Flo , Taylor Rachel M
Published: May 2021

Aims

To determine how the learning about protective factors from previous pandemics were implemented and the impact of this on nurses’ experience.

Background

The COVID-19 pandemic led to systemic change within healthcare settings and demands placed on frontline nurses has been overwhelming. Lessons learned from previous pandemics indicate that clear communication and strong visible leadership can mitigate the impact stressful events may have on nurses. Conversely, a lack of clear leadership and regulatory protocols in times of crisis can lead to an increase in psychological distress for nurses.

Design

Secondary analysis of semi-structured interview transcripts.

Methods

Secondary data analysis was conducted on data collected during a hospital-wide evaluation of barriers and facilitators to changes implemented to support the surge of COVID-19 related admissions in wave one of the pandemic. Participants represented three-levels of leadership: whole trust (n=17), division (n=7), ward/department-level (n=8), and individual nurses (n=16). Data were collected through semi-structured video interviews between May and July 2020. Interviews were analysed using Framework analysis.

Results

Key changes that were implemented in wave one reported at whole trust level included: a new acute staffing level, redeploying nurses, increasing the visibility of nursing leadership, new staff wellbeing initiatives, new roles created to support families and various training initiatives. Two main themes emerged from the interviews at division, ward/department and individual nurse level: impact of leadership, and impact on the delivery of nursing care.

Conclusions

Leadership through a crisis is essential for the protective effect of nurses’ emotional wellbeing. While nursing leadership was made more visible during wave one of the pandemic and processes were in place to increase communication, system-level challenges resulting in negative experiences existed. By identifying these challenges, it has been possible to overcome them during wave two by employing different leadership styles, to support nurse wellbeing