bluuebunny/crossref_metadata_2025 huggingface dataset:
Chronic Kidney Disease as a Predictor of Postoperative Choroidal Effusions After Glaucoma Surgery
Authors: Ford Richard L. , Klifto Meredith R. , Knight O’Rese J. , Jain Koyal , Wiesen Chris , Fleischman David
Published: July 2021

Précis:

Patients with chronic kidney disease (CKD) are at increased risk for choroidal effusion development following glaucoma surgery.

Purpose:

Choroidal effusion is a postoperative complication of glaucoma surgery that results from a transudative fluid collection in the suprachoroidal space. Kidney disease alters bodily fluid dynamics through a variety of mechanisms. The relationship between CKD and choroidal effusion following glaucoma surgery has not previously been studied. The purpose of this study was to determine the relationship between CKD and choroidal effusion development after glaucoma surgery.

Patients and Methods:

This retrospective cohort study consisted of 86 eyes from 86 patients who received glaucoma filtering surgery or transscleral cyclophotocoagulation within the study timeframe. Forty-three patients had CKD, and 43 patients did not have kidney disease. The main outcome of this study was the development of choroidal effusion measured by the Pearson χ2 test and multivariate analysis using a binomial regression with a log link.

Results:

Ten patients (23.3%) in the CKD group developed choroidal effusion, while 2 patients (4.7%) in the no-kidney disease group developed choroidal effusion (relative risk, 5.0; 95% confidence interval: 1.16-21.5; P=0.013). The association between CKD and choroidal effusion showed mixed results in the multivariate analysis, with some analyses showing a significant association and others showing no significant association.

Conclusions:

In both the univariate and multivariate analyses, CKD was found to be significantly associated with choroidal effusion after glaucoma surgery.
Dysphotopsia and functional quality of vision after implantation of an intraocular lens with a 7.0 mm optic and plate haptic design
Authors: Bonsemeyer Małgorzata Kalina , Becker Eckhard , Liekfeld Anja
Published: July 2021

Purpose:

To determine the impact of an intraocular lens (IOL) with a 7.0 mm optic and plate haptic design on incidence of dysphotopsia and visual functions after cataract surgery.

Setting:

Day-care clinic.

Design:

Prospective monocentric randomized patient-blinded comparative clinical study.

Methods:

Following preoperative measurements, patients underwent cataract surgery with implantation of 2 IOL designs—with 7.0 mm optic and plate haptics (Group 1) or with 6.0 mm optic and C-loop haptics (Group 2). In month 1, 3, and 12 follow-ups, patients were examined, answered a questionnaire regarding satisfaction, spectacle dependence, frequency, and extent of positive and negative dysphotopsia, and underwent contrast sensitivity (CS), mesopic vision, and glare sensitivity testing. The data were analyzed as nominal, ordinal, and metric with chi-square, Mann-Whitney U, Wilcoxon, and t tests.

Results:

Out of a total number of 120 eyes (86 patients), Group 1 comprised 57 eyes (43 patients), Group 2 comprised 63 eyes (43 patients). Corrected distance visual acuity was the same between groups throughout the study. Group 1 showed significantly lower incidence of positive and negative dysphotopsia in month 1 follow-up (P = .021 and .015, respectively) and a higher satisfaction rate in month 3 follow-up (P = .006). Mean CS and mesopic vision with and without glare were the same in both groups. Positive dysphotopsia cases in month 12 follow-up revealed lower photopic CS (P = .005, .036, and 0.047, respectively), longer axial length, and greater preoperative pupil dynamics (P = .04 and .06).

Conclusions:

The IOL design with 7.0 mm optic diameter and plate haptics reduced dysphotopsia and provided good visual acuity, CS, mesopic vision with and without glare, and high patient satisfaction.
A Comparison of Medication-Assisted Treatment Options for Opioid Addiction
Authors: Spayde-Baker Amanda , Patek Jennifer
Published: July 2021

In individuals in the United States with opioid addiction, what is the effect of a medication-assisted treatment (MAT) in reducing the relapse and harm reduction when comparing the use of buprenorphine, methadone, and naltrexone? In 2017, it was estimated that 1.7 million individuals suffer from overuse of prescription opiates, 652,000 individuals suffer from heroin use disorder, and greater than 130 individuals die from opiate overdose daily (National Institutes of Health, 2019). Using a systematic literature review, the following results were found. Buprenorphine is currently the second most effective MAT in harm reduction and relapse prevention, can be initiated and maintained through primary care, has a low risk for overdose, but needs to be started only when moderate withdrawals have begun. Methadone is currently the gold standard in MAT and can be started in any stage of withdrawal; however, titrating to effective dose is a lengthy process, and it must be administered at a specialty clinic. Naltrexone in oral form has not been shown to be effective because of lack of adherence; however, the extended-release intramuscular injection form has been shown to reduce relapse and increase the quality of life before initiation individuals must be opioid free for 7–14 days. Choosing the proper MAT is highly individualized. It is recommended that more research be conducted in comparing all MAT options, looking at the quality of life on each MAT, researching motivations to stay on MAT and remain opioid free, and looking at the impact of external reward on adherence to the MAT program.
The Role of Intestinal Microbiota in Atopic Dermatitis
Authors: Zuo Wen , Sun Cai-Hong
Published: July 2021

The early intestinal microbiota plays an important role in immune regulation, and the unbalanced composition may increase the occurrence of allergic diseases, including atopic dermatitis. This review summarizes the latest studies in the occurrence and development of intestinal microflora and its relationship with atopic dermatitis. These results are conducive to understand the differences in the composition of intestinal microbiota between patients with atopic dermatitis and healthy people, and provide a potential intervention for prevention or treatment of atopic dermatitis.
Comparison of Sagittal Plane Stiffness of Nonarticulated Pediatric Ankle-Foot Orthoses Designed to be Rigid
Authors: Fatone Stefania , Owen Elaine , Gao Fan , Shippen Garth , Orendurff Michael S. , Bjornson Kristie
Published: July 2021

Introduction

When studying the effect of ankle-foot orthoses (AFOs) on gait, it is important to know their sagittal plane stiffness. However, there are no established thresholds for stiffness of nonarticulated AFOs designed to be rigid. If wanting to implement published algorithms for ankle-foot orthosis-footwear combinations (AFO-FCs), the AFOs must be equally as stiff as those of the developer of the published AFO-FC algorithms. Hence, the aim of this work was to compare the sagittal plane stiffness of AFOs designed to be rigid, made for a clinical trial in the United States, and following algorithms for AFO-FC designs, to those made and used clinically in the United Kingdom by the developer of the AFO-FC algorithms.

Materials and Methods

Stiffness of nine pediatric polypropylene AFOs was tested (United Kingdom, six; United States, three). A computer-controlled motorized device was used in which all AFOs were clamped with the calf shell in a fixed vertical component and the foot section in a rotating plate. Each AFO was tested for three trials, loading the foot plate 30 Nm toward dorsiflexion and 20 Nm toward plantarflexion. Torque-angle graphs were plotted, and deflection and stiffness were compared descriptively across AFOs.

Results

Average deflection of AFOs was 3.42° ± 0.83° for United Kingdom and 4.81° ± 1.05° for United States. Average stiffness of AFOs was 14.34 ± 3.34 Nm/° for United Kingdom and 10.30 ± 1.92 Nm/° for United States.

Conclusions

All tested AFOs deflected only a few degrees in either direction (range, 2.59°–6.02°), providing the first information reported for the stiffness of rigid pediatric nonarticulated AFOs. Overall, the UK AFOs were stiffer and deflected less than the US study AFOs. AFO design features should be carefully considered as they likely influence sagittal plane stiffness and deflection under load.
A Standardized Approach Improves Outcomes of Extracorporeal Membrane Oxygenation for Postcardiotomy Shock
Authors: Ogami Takuya , Takayama Hiroo , Melehy Andrew , Witer Lucas , Kaku Yuji , Fried Justin , Masoumi Amirali , Brodie Daniel , Takeda Koji
Published: July 2021

Postcardiotomy shock (PCS) has historically been associated with substantial morbidity and mortality. Mortality at discharge is reportedly more than 60%. We investigated the outcomes of our standardized approach to veno-arterial extracorporeal membrane oxygenation (ECMO) management for PCS. We retrospectively reviewed 60 consecutive PCS patients who required ECMO following major cardiac surgery from January 2017 to September 2019. Index surgery included CABG (n = 10), valve (n = 23), valve and CABG (n = 12), root surgery (n = 10), and other (n = 5). Median lactate level, systolic blood pressure, and mean pulmonary artery pressure before ECMO were 4.0 mmol/L, 80 mm Hg, and 29 mm Hg, respectively. Fifty-nine patients (98%) were on two vasopressors, and 54 (90%) were on at least two inotropes. Vasoactive-Inotropic Score was 30 (IQR, 25–49). Eighty percent of patients received peripheral ECMO. Median ECMO flow index was 1.61 (IQR, 1.4–2.0) L/min/m2. Anticoagulation was not given in 12 (20%) patients during ECMO support. Major adverse events included chest re-exploration (15%), stroke (6.7%), renal replacement therapy (22%), and limb ischemia (5%). In-hospital mortality was 33%. This study suggests that a standardized approach with a dedicated ECMO team is feasible and may improve outcomes of PCS.
Balloon pulmonary angioplasty for chronic thromboembolic pulmonary hypertension: advances in patient and lesion selection
Authors: Shimokawahara Hiroto , Ogawa Aiko , Matsubara Hiromi
Published: July 2021

Purpose of review

Balloon pulmonary angioplasty (BPA) has been performed worldwide for patients who are ineligible for pulmonary endarterectomy (PEA). However, the technical details of BPA have not been standardized, and no international consensus regarding patient and lesion selection for BPA has been reached. Evidence for the combination of BPA with PEA or medical therapy is also lacking. This review highlights recent progress in BPA in terms of patient and lesion selection and the current procedural approach for BPA, including combination treatment.

Recent findings

The indications for BPA have expanded with recent reports describing the improved safety and efficacy of BPA. Because lesions are generally present in all segmental and subsegmental pulmonary arteries, it is recommended to treat all the lesions to achieve desirable hemodynamic improvement. Selective pulmonary angiography is the gold standard for lesion selection in modern BPA aimed at total revascularization. Despite the lack of randomized controlled studies, combination treatment with BPA may be well tolerated and effective.

BPA, alone or in combination with PEA or medical therapy, may be a treatment option for patients who are not candidates for monotreatment of PEA. However, further investigation is required to standardize patient and lesion selection for BPA.
Angiosarcoma of the Pancreas in a Pediatric Patient With an Activating KDR-Internal Tandem Duplication: A Case Report and Review of the Literature
Authors: Whitlock Richard S. , Ebare Kingsley , Cheng Lily S. , Fishman Douglas S. , Mills Joseph L. , Nguyen HaiThuy N. , Nuchtern Jed G. , Ruan Wenly , Smith Valeria E. , Patel Kalyani A. , Fisher Kevin E. , Vasudevan Sanjeev A.
Published: July 2021

Pancreatic angiosarcoma is an exceedingly rare malignancy accounting for <1% of pancreatic neoplasms. A very limited number of pancreatic angiosarcomas have been reported in the literature without any cases described in children. We present the case of a 17-year-old female diagnosed with angiosarcoma of the pancreas following pancreaticoduodenectomy for a pancreatic mass, initially presumed to be a solid pseudopapillary neoplasm of the pancreas. The angiosarcoma was found to have a novel activating internal tandem duplication in the KDR gene (KDR-internal tandem duplication). We discuss the current literature on this disease process. This is the first reported case of pancreatic angiosarcoma in a pediatric patient and the first with an activating KDR-internal tandem duplication.
The Ever-Changing Work Environment During COVID-19
Authors: Nair Julie McCulloh , Birkhoff Susan , Mandel Deborah , Thomas Amanda
Published: July 2021

The COVID-19 pandemic is a history-changing event affecting all nurses. This study sought to explore nurses’ experiences during the pandemic’s early phase using a phenomenological approach. One hundred sixty-one participants enrolled in the study. Demographic data, written narratives, and digital images were collected. Ever-changing environment emerged as the overarching theme, along with six subthemes. Because of a crisis situation created by the pandemic, nurses need specialized support and education to manage their constantly changing environment.
Effects of Slide Storage on Detection of Molecular Markers by IHC and FISH in Endometrial Cancer Tissues From a Clinical Trial: An NRG Oncology/GOG Pilot Study
Authors: Grushko Tatyana A. , Filiaci Virginia L. , Montag Anthony G. , Apushkin Marsha , Gomez Maria J. , Monovich Laura , Ramirez Nilsa C. , Schwab Carlton , Kesterson Joshua P. , Seward Shelly M. , Method Michael W. , Olopade Olufunmilayo I. , Fleming Gini F. , Birrer Michael J.
Published: July 2021

We performed a pilot study in anticipation of using long-aged precut formalin-fixed paraffin-embedded tissue sections stored in real-world conditions for translational biomarker studies of topoisomerase 2A (TOP2A), Ki67, and human epidermal growth factor receptor 2 (HER2) in endometrial cancer. Formalin-fixed paraffin-embedded tissue blocks or unstained slides or both from GOG-0177 were collected centrally (1999-2000) and stored at room temperature. During 2004 to 2011 specimens were stored at 4°C. Matched pairs of stored slides and freshly cut slides from stored blocks were analyzed for TOP2A (KiS1), Ki67 (MIB1), and HER2 (HercepTest) proteins. To assess DNA stability (HER2 PathVision), fluorescence in situ hybridization (FISH) was repeated on stored slides from 21 cases previously shown to be HER2 amplified. Immunohistochemistry (IHC) staining intensity and extent, mean FISH copies/cell, and copy number ratios were compared using the κ statistic for concordance or signed rank test for differences in old cut versus new cut slides. IHC results reflected some protein degradation in stored slides. The proportion of cells with TOP2A staining was lower on average by 12% in older sections (P=0.03). The proportion of Ki67-positive cells was lower in stored slides by an average of 10% (P<0.01). Too few cases in the IHC cohort were FISH positive for any conclusions. HER2 amplification by FISH was unaffected by slide storage. We conclude that use of aged stored slides for proliferation markers TOP2A and Ki67 is feasible but may modestly underestimate true values in endometrial cancer. Pilot studies for particular storage conditions/durations/antigens to be used in translational studies are warranted.
Transient Severe Motion Artifact on Arterial Phase in Gadoxetic Acid-Enhanced Liver Magnetic Resonance Imaging
Authors: Kim Dong Wook , Choi Sang Hyun , Park Taeyong , Kim So Yeon , Lee Seung Soo , Byun Jae Ho
Published: July 2021

Objectives

The aims of this study were to determine the incidence of transient severe motion artifact (TSM) on arterial phase gadoxetic acid-enhanced magnetic resonance imaging of the liver and to investigate the causes of heterogeneity in the published literature.

Materials and Methods

Original studies reporting the incidence of TSM were identified in searches of PubMed, Embase, and Cochrane Library databases. The pooled incidence of TSM was calculated using random-effects meta-analysis of single proportions. Subgroup analyses were conducted to explore causes of heterogeneity.

Results

A total of 24 studies were finally included (single arterial phase, 19 studies with 3065 subjects; multiple arterial phases, 8 studies with 2274 subjects). Studies using single arterial phase imaging reported individual TSM rates varying from 4.8% to 26.7% and a pooled incidence of TSM of 13.0% (95% confidence interval, 10.3%–16.2%), which showed substantial study heterogeneity. The pooled incidence of TSM in the studies using multiple arterial phase imaging was 3.2% (95% confidence interval, 1.9%–5.2%), which was significantly less than in those studies using single arterial phase imaging (P < 0.001). In the subgroup analysis, the geographical region of studies and the definition of TSM were found to be causes of heterogeneity. The incidence of TSM was higher in studies with Western populations from Europe or North America than in those with Eastern (Asia/Pacific) populations (16.0% vs 8.8%, P = 0.005). Regarding the definition of TSM, the incidence of TSM was higher when a 4-point scale was used for its categorization than when a 5-point scale was used (20.0% vs 11.0%, P = 0.008), and a definition considering motion artifact on phases other than arterial phase imaging lowered the incidence of TSM compared with it being defined only on arterial phase imaging (11.3% vs 20.3%, P = 0.018).

Conclusions

The incidence of TSM on arterial phase images varied across studies and was associated with the geographical region of studies and the definition of TSM. Careful interpretation of results reporting TSM might therefore be needed.
Upper Airway Characteristics in Young Individuals With Class II Division 1 Malocclusion: A Retrospective Inter-Ethnic Cephalometric Comparison
Authors: Al Ayoubi Alaa , Madléna Melinda
Published: July 2021

This study aimed to compare the upper-airway morphology between strictly matched Syrian (n = 43) and Hungarian (n = 43) adolescents with Class II/1 malocclusion and identify potential associations between upper airway depths and skeletofacial characteristics. Lateral cephalograms were analyzed, and independent-samples tests and correlation coefficients were used for the statistical analyses. The upper-pharyngeal airway was significantly narrower and the soft palate angle was significantly greater in the Syrian adolescents. Alternatively, the hyoid bone was more posteriorly positioned in the Hungarian adolescents when compared to their counterparts. Depths of the upper and middle pharynx were moderately correlated with sagittal and vertical skeletal dimensions only among Syrian subjects. The depth of the lower pharynx was moderately correlated with hyoid bone position, cervical length, and lip–chin–throat angle only among Hungarian subjects. These findings might have potential implications for optimizing the effects of orthognathic/orthodontic treatments on airway structures in these 2 groups.
Application of Three-Dimensional Printed Customized Surgical Plates for Mandibular Reconstruction: Report of Consecutive Cases and Long-Term Postoperative Evaluation
Authors: Ma Hongyang , Van Dessel Jeroen , Bila Michel , Sun Yi , Politis Constantinus , Jacobs Reinhilde
Published: July 2021

This study aims to evaluate the use of customized surgical plates in patients with mandibular defects concerning postoperative aesthetics and functional outcomes during the 2-year follow-up. Preoperative virtual surgical plans and patient-specific three-dimensional printed plates were tailored for consecutive patients. Preoperative preparation, surgical produces, postoperative aesthetics, and functional outcomes were described in detail. The average follow-up period was over 2 years. In the presented clinical cases, aesthetic and functional outcomes were reported to be satisfactory.
A Novel Three-Dimensional Robot Arm Steered Camera for Ear Surgery
Authors: Tekin Ahmet M. , Saadi Mohammad Al , Topsakal Vedat
Published: July 2021

Ear surgery requires magnified imaging of anatomical structures from its beginning to achieve safe and successful surgical outcomes. The historical evolution of magnification in otology has developed from monocular to binocular, and to three-dimensional and even to digital in modern times. Current technological advancements pursue high-quality visualization for the best surgical outcomes but also ergonomic for surgeons. Here, we evaluated the usability of such new technology in common otological surgeries like cochlear implantation and stapedectomy for the first time in patients. A three-dimensional camera mounted to a robot arm has hands-free control by goggles worn by the surgeon on a head mount. The camera at a distance of the patients but can also be draped in a sterile way that it forms a barrier tent between patient and surgical personnel in the theatre. The main reason to evaluate the feasibility of this new exoscope was driven by COVID-19 obligate measures for elective surgery such as hearing restoration. This new technology can be considered an important advantage for the surgeons working in microsurgery to perform their elective operations without aerosolization of the drill rinsing water possibly containing contaminated tissue. From a subjective point of view, the image quality is equivalent to conventional microscopes to provide safe otologic surgery.
Missense Variants Within GJB2 Gene Locus and the Risk of Hearing Defects in Nonsyndromic Cleft Lip and Palate
Authors: Adeyemo Wasiu Lanre , James Olutayo , Bamigboye Babatunde A. , Akinola Moronke D. , Adamson Olawale O. , Nkemjika Benjamin N. , Ibikunle Adebayo A. , Ogunlewe Mobolanle O. , Ladeinde Akinola L. , Butali Azeez
Published: July 2021

Aim:

The aim of the study was to investigate the role of variants in GJB2 gene in the etiology of hearing defects in nonsyndromic cleft lip/palate.

Method:

Saliva samples were obtained from cases (subjects with orofacial clefts) and control (subjects without orofacial clefts) who consented to the study. Deoxyribonucleic acid (DNA) was extracted using standardized protocol at Butali Lab (Iowa, IA). Primers for the coding region of GJB2 was designed using Primer 3 (http://bioinfo.ut.ee/primer3-0.4.0/) and optimized in the Butali lab using a gradient polymerase chain reaction to determine the annealing temperature for each primer set (forward and reverse). We measured the DNA concentration using Qubit and XY genotyping done for quality control. A concentration of 5 ng/μL of DNA was used for Sanger sequencing.

Results:

A total of 150 subjects were sequenced (66 cases; 84 controls). Mutations in GJB2 gene were detected in 2 individuals with cleft palate. We found p.Arg165Trp variant in 1 case and p.Leu81Val variant in the second case. Although p.Arg165Trp was predicted to be either benign or tolerated by SIFT/POLYPHEN, the single nucleotide change from C>T, that is, CGG>TGG leads to a premature stop codon preventing the protein formation. The p.Leu81Val variant was predicted to be probably damaging/ deleterious.

Conclusions:

The present study implicates variants in the GJB2 gene in the etiology of hearing defects in nonsyndromic cleft lip and palate in the Nigerian population. Screening for variations in GJB2 gene is important for genetic counseling especially in high-risk families.
Ergonomics Among Craniofacial Surgeons: A Survey of Work-Related Musculoskeletal Discomfort and Injury
Authors: Shah Jinesh , Wang Fei , Kest Joshua , Greige Nicolas , Sandoval Tyler , Nash David , Tepper Oren , Ricci Joseph A.
Published: July 2021

Introduction:

Surgical procedures with loupe magnification, headlights, and microscopes expose craniofacial surgeons to mechanical stress that can increase risk of long-term musculoskeletal pain and injury. Identifying the prevalence and cause of work-related musculoskeletal discomfort may guide preventative strategies to prolong well-being, job satisfaction, and greater duration of surgical careers.

Methods:

A 29-question online survey was distributed to the surgeon members of the American Cleft Palate-Craniofacial Association. Eight hundred seventy-three surveys were distributed, and the anonymous responses were recorded using Google forms.

Results:

One hundred ninety-six unique responses were recorded (22.5% response rate). A total of 64.2% reported experiencing musculoskeletal symptoms during their career, with neck, lower back, and shoulders being the most common problem areas. Multivariate analysis demonstrated surgical loupes (odds ratio 2.36, P = 0.03) and length of surgical practice >15 years (odds ratio 1.95, P = 0.04) were independently associated with greater odds of developing symptoms. Headlights (median pain = 3, P < 0.001), loupes (median pain = 3.5, P < 0.001), and operative microscope use (median pain = 2, P = 0.02) were all associated with higher pain while operating. A total of 52.5% respondents sought medical treatments, 50.5% were concerned musculoskeletal discomfort would affect their careers, 56.6% reported a colleague that required an operation, and 30.2% reported a colleague on temporary or permanent disability.

Conclusions:

Craniofacial surgery often involves long procedures, use of surgical adjuncts, and ergonomically straining postures, which can lead to musculoskeletal discomfort and injury. This under-reported and important phenomenon merits candid conversation and active preventative strategies to prolong surgical careers, improve professional satisfaction, and maximize patient safety.
A Heart Surgery Simulator With an Integrated Supervision System for Self-Learning the Key Steps and Pitfalls of the Mitral Valve Repair
Authors: Tozzi Piergiorgio , Solida Alessandra , Siniscalchi Giuseppe , Ferrari Enrico
Published: July 2021

Introduction

Over the years, surgical education has dramatically improved and has become increasingly innovative. Almost all educational programs in surgery now rely on sophisticated training boxes and simulators that enable surgical instruments to be handled and surgical procedures to be trained in a safe environment. However, simulators need constant feedback from supervising senior surgeons, who only have limited teaching time available. We describe a cardiac surgery simulator with an integrated supervision system for self-learning how to repair a mitral valve.

Methods

We developed a mitral surgery simulator with integrated sensors to generate, record, and display quantitative data on trainee performance in relation with the mitral valve repair procedure. A team of experienced cardiac surgeons defined critical areas of the model and an algorithm to identify inconsistent movements, in terms of error types and out-of-bound actions. The device provided real-time feedback on the accuracy of the stitches placed. Four experienced cardiac surgeons and 3 advanced cardiac-surgery used the simulator and were asked to evaluate specific parameters of the system on a scale ranging from 1 to 10.

Results

All surgeons completed a P2 resection, followed by implanting a 32-mm mitral ring. The simulator detected 2 stitches that were placed in dangerous zones and another stitch that was placed in an inappropriate position. Users scored the real tissue feeling and interactivity of the model 9.5/10.

Conclusions

This heart-surgery simulator offers a real-life model for learning about and training in mitral valve surgery, which could potentially replace the experienced surgeon's teaching role.
Optic Perineuritis Presenting as the Initial Manifestation of Central Nervous System Involvement in Rai Stage 0 Chronic Lymphocytic Leukemia
Authors: Parker James L. , Mays Kevin M. , Pratibhu Parakash P. , Pick Peter W. , Block Danielle K.
Published: July 2021

Background:

To describe the first case of optic perineuritis because of meningeal involvement of early stage chronic lymphocytic leukemia (CLL).

Methods:

A case report and review of the literature.

Results:

A case of unilateral optic neuropathy associated with enhancement of the optic nerve sheath is described in a patient with a prior 2-year history of Rai Stage 0 CLL. Lumbar puncture revealed a lymphocytic pleocytosis. Cerebrospinal fluid flow cytometry revealed a monoclonal expansion of CD5+ B cells compatible with CLL, matching the flow cytometry characteristics of his peripheral blood.

Conclusions:

Optic perineuritis is often initially diagnosed as optic neuritis, yet the 2 have different etiologies and follow a different clinical course. Orbital MRI with contrast structurally separates the 2, revealing a characteristic pattern of peripheral optic nerve sheath rather than primary optic nerve enhancement. Etiologies of optic perineuritis are varied and include inflammatory, infectious, neoplastic, and toxic entities. Central nervous system (CNS) involvement by chronic lymphocytic leukemia is unusual, but cranial nerve and meningeal involvement have been reported. This case adds central nervous system chronic lymphocytic leukemia to the list of differential diagnostic possibilities for optic perineuritis. It also alerts clinicians to consider optic perineuritis as a potential presenting feature of CNS involvement in otherwise asymptomatic and stable CLL.
Modified kernel MLAA using autoencoder for PET-enabled dual-energy CT
Authors: Li Siqi , Wang Guobao
Published: July 2021

Combined use of PET and dual-energy CT provides complementary information for multi-parametric imaging. PET-enabled dual-energy CT combines a low-energy X-ray CT image with a high-energy
γ
-ray CT (GCT) image reconstructed from time-of-flight PET emission data to enable dual-energy CT material decomposition on a PET/CT scanner. The maximum-likelihood attenuation and activity (MLAA) algorithm has been used for GCT reconstruction but suffers from noise. Kernel MLAA exploits an X-ray CT image prior through the kernel framework to guide GCT reconstruction and has demonstrated substantial improvements in noise suppression. However, similar to other kernel methods for image reconstruction, the existing kernel MLAA uses image intensity-based features to construct the kernel representation, which is not always robust and may lead to suboptimal reconstruction with artefacts. In this paper, we propose a modified kernel method by using an autoencoder convolutional neural network (CNN) to extract an intrinsic feature set from the X-ray CT image prior. A computer simulation study was conducted to compare the autoencoder CNN-derived feature representation with raw image patches for evaluation of kernel MLAA for GCT image reconstruction and dual-energy multi-material decomposition. The results show that the autoencoder kernel MLAA method can achieve a significant image quality improvement for GCT and material decomposition as compared to the existing kernel MLAA algorithm. A weakness of the proposed method is its potential over-smoothness in a bone region, indicating the importance of further optimization in future work.

This article is part of the theme issue ‘Synergistic tomographic image reconstruction: part 2’.
Exploring the evolution and epidemiology of European CC1-MRSA-IV: tracking a multidrug-resistant community-associated meticillin-resistant Staphylococcus aureus clone
Authors: Earls Megan R. , Steinig Eike J. , Monecke Stefan , Samaniego Castruita José A. , Simbeck Alexandra , Schneider-Brachert Wulf , Vremerǎ Teodora , Dorneanu Olivia S. , Loncaric Igor , Bes Michèle , Lacoma Alicia , Prat Aymerich Cristina , Wernery Ulrich , Armengol-Porta Marc , Blomfeldt Anita , Duchene Sebastian , Bartels Mette D. , Ehricht Ralf , Coleman David C.
Published: July 2021

This study investigated the evolution and epidemiology of the community-associated and multidrug-resistant

Staphylococcus aureus

clone European CC1-MRSA-IV. Whole-genome sequences were obtained for 194 European CC1-MRSA-IV isolates (189 of human and 5 of animal origin) from 12 countries, and 10 meticillin-susceptible precursors (from North-Eastern Romania; all of human origin) of the clone. Phylogenetic analysis was performed using a maximum-likelihood approach, a time-measured phylogeny was reconstructed using Bayesian analysis, and in silico microarray genotyping was performed to identify resistance, virulence-associated and SCCmec (staphylococcal cassette chromosome mec) genes. Isolates were typically sequence type 1 (190/204) and spa type t127 (183/204). Bayesian analysis indicated that European CC1-MRSA-IV emerged in approximately 1995 before undergoing rapid expansion in the late 1990s and 2000s, while spreading throughout Europe and into the Middle East. Phylogenetic analysis revealed an unstructured meticillin-resistant

S. aureus

(MRSA) population, lacking significant geographical or temporal clusters. The MRSA were genotypically multidrug-resistant, consistently encoded seh, and intermittently (34/194) encoded an undisrupted hlb gene with concomitant absence of the lysogenic phage-encoded genes sak and scn. All MRSA also harboured a characteristic ~5350 nt insertion in SCCmec adjacent to orfX. Detailed demographic data from Denmark showed that there, the clone is typically (25/35) found in the community, and often (10/35) among individuals with links to South-Eastern Europe. This study elucidated the evolution and epidemiology of European CC1-MRSA-IV, which emerged from a meticillin-susceptible lineage prevalent in North-Eastern Romania before disseminating rapidly throughout Europe.
Men and loneliness in the Covid-19 pandemic: insights from an interview study with UK-based men
Authors: Ratcliffe John , Galdas Paul , Kanaan Mona
Published: July 2021

As the SARS-COV-2 pandemic hit, the UK, like many countries, introduced severe restrictions on social contact, and injunctions of ‘social distancing’, to reduce transmission. This led to a concern that loneliness may increase, facilitating poorer mental and physical health. Twenty qualitative interviews were conducted, with a diverse group of UK-based men, between January and March 2021, during severe restrictions. Our aim was to generate new insights into men’s experience of loneliness during the pandemic, and consider the ramifications of these for continued/future restrictions, the easing of restrictions, and the future beyond the pandemic. Thematic analysis, focused on semantic themes, was employed as part of a ‘grounded’ epistemology whereby the stated perspectives of the interviewees drove the content of the study. Six themes were constructed: i) people to see and things to do (broken, changed, and new); ii) rethought and renewed recognition of what is important; iii) loneliness with a purpose; iv) loneliness as normal; v) anxiety of social contact; and vi) easier for some than others. The restrictions did cause some loneliness, particularly because of lost routines and opportunities, and the reduction in face-to-face interaction. However, a need to reduce transmission of SARS-COV-2, and a fear of catching it, became important features of participants lives that also affected loneliness and its causes. Remote forms of interaction were often utilised, and though they were imperfect, those that were dependable, were smaller than might be desired in person, and ensured a chance to speak, were constructed as more positive. The fear of Covid-19, and a loss of social skills, may mean that reducing restrictions alone will not return everyone to pre-pandemic levels of loneliness. Some believed the building of supportive local communities, and a destigmatisation of loneliness, may allow for the building of a more compassionate and less lonely society.

What is known about this topic

Loneliness is a public health concern, and is often a gendered experience.

Pandemic related restrictions greatly reduced opportunities for social contact.

We have a limited understanding of whether, and how, men experienced loneliness during the SARS-COV-2 pandemic.

What this paper adds

The loss of routines, and a lack of face-to-face interaction, were the greatest challenges to loneliness, particularly among solo-living men.

Remote interaction may be better when routinised or dependable, in smaller groups, and with a structure facilitating the opportunity to speak.

Anxiety of SARS-COV-2, and identities built in relation to reducing transmission, were important influences on the causes and severity of loneliness.
DNA methylome-wide association study of genetic risk for depression implicates antigen processing and immune responses
Authors: Shen Xueyi , Caramaschi Doretta , Adams Mark J , Walker Rosie M , Min Josine L , Kwong Alex , Hemani Gibran ,   Genetics of DNA Methylation Consortium, Barbu Miruna C , Whalley Heather C , Harris Sarah E , Deary Ian J , Morris Stewart W , Cox Simon R , Relton Caroline L , Marioni Riccardo E , Evans Kathryn L , McIntosh Andrew M
Published: July 2021

Background

Depression is a disabling and highly prevalent condition where genetic and epigenetic differences, such as DNA methylation (DNAm), contribute to prediction of disease liability.

Method

We investigated the association between polygenic risk scores (PRS) for depression and DNAm by conducting a methylome-wide association study (MWAS) in Generation Scotland (N=8,898, mean age=49.8 years) with replication in the Lothian Birth Cohorts of 1921 and 1936 and adults in Avon Longitudinal Study of Parents and Children (ALSPAC) (Ncombined=2,049, mean age=79.1, 69.6 and 47.2 years, respectively). We also conducted a replication MWAS in the ALSPAC children (N=423, mean age=17.1 years).

Result

Wide-spread associations were found between PRS constructed using genetic risk variants for depression and DNAm in cytosine-guanine dinucleotide (CpG) probes that localised to genes involved in immune responses and neural development (NCpG=599, pBonferroni<0.05, p<6.5×10−8). The effect sizes for the significant associations were highly correlated between the discovery and replication samples in adults (r=0.83) and in adolescents (r=0.76). Additional analysis on the methylome-wide associations was conducted for each lead genetic risk variant. Over 40% of the independent genetic risk variants showed associations with CpG probe DNAm located in both the same (cis) and distal probes (trans) to the genetic loci (pBonferroni<0.045). Subsequent Mendelian randomisation analysis showed that DNAm and depression are mutually causal (pFDR<0.039), and there is a greater number of causal effects found from DNAm to depression (DNAm to depression: pFDR ranged from 0.045 to 2.06×10−120; depression to DNAm: pFDR ranged from 0.046 to 2.1×10−23).

Conclusion

Polygenic risk scores for depression, especially those constructed from genome-wide significant genetic risk variants, showed epigenome-wide methylation association differences in the methylome associated with immune responses and brain development. We also found evidence from Mendelian randomisation evidence that DNAm may be causal to depression, as well as a causal consequence of depression.
Urinary cell mRNA Profiling of Kidney Allograft Recipients: A Systematic Investigation of a Filtration Based Protocol for the Simplification of Urine Processing
Authors: Snopkowski Catherine , Salinas Thalia , Li Carol , Stryjniak Gabriel , Ding Ruchuang , Sharma Vijay , Suthanthiran Manikkam
Published: July 2021

Background

Kidney transplantation is a life-restorative therapy, but immune rejection undermines allograft survival. Urinary cell mRNA profiles offer a noninvasive means of diagnosing kidney allograft rejection, but urine processing protocols have logistical constraints. We aimed to determine whether the centrifugation-based method for urinary cell mRNA profiling could be replaced with a simpler filtration-based method without undermining quality.

Methods

We isolated RNA from urine collected from kidney allograft recipients using the Cornell centrifugation-based protocol (CCBP) or the Zymo filter-based protocol (ZFBP) and compared RNA purity and yield using a spectrophotometer or a fluorometer and measured absolute copy number of transcripts using customized real-time quantitative PCR assays. We investigated the performance characteristics of RNA isolated using ZFBP and stored either at - 80°C or at ambient temperature for 2 to 4 days and also when shipped to our Gene Expression Monitoring (GEM) Core at ambient temperature. We examined the feasibility of initial processing of urine samples by kidney allograft recipients trained by the GEM Core staff and the diagnostic utility for acute rejection, of urine processed using the ZFBP.

Results

RNA purity (P=0.0007, Wilcoxon matched paired signed-ranks test) and yield (P<0.0001) were higher with ZFBP vs. CCBP, and absolute copy number of 18S rRNA was similar (P=0.79) following normalization of RNA yield by reverse transcribing a constant amount of RNA isolated using either protocol. RNA purity, yield, and absolute copy numbers of 18S rRNA, TGF-β1 mRNA and microRNA-26a were not different (P>0.05) in the filtrates containing RNA stored either at -80°C or at ambient temperature for 2 to 4 days or shipped overnight at ambient temperature. RNA purity, yield, and absolute copy numbers of 18S rRNA and TGF-β1 mRNA were also not different (P>0.05) between home processed and laboratory processed urine filtrates. Urinary cell levels of mRNA for granzyme B (P=0.01) and perforin (P=0.0002) in the filtrates were diagnostic of acute rejection in human kidney allografts.

Conclusions

Urinary cell mRNA profiling was simplified using the ZFBP without undermining RNA quality or diagnostic utility. Home processing by the kidney allograft recipients, the stability of RNA containing filtrates at ambient temperature, and the elimination of the need for centrifuges and freezers represent some of the advantages of ZFBP over the CCBP for urinary cell mRNA profiling.
Phylogeography and transmission of M. tuberculosis in Moldova
Authors: Yang Chongguang , Sobkowiak Benjamin , Naidu Vijay , Codreanu Alexandru , Ciobanu Nelly , Gunasekera Kenneth S. , Chitwood Melanie H. , Alexandru Sofia , Bivol Stela , Russi Marcus , Havumaki Joshua , Cudahy Patrick , Fosburgh Heather , Allender Christopher J. ,   Heather Centner, Engelthaler David M. , Menzies Nicolas A. , Warren Joshua L. , Crudu Valeriu , Colijn Caroline , Cohen Ted
Published: July 2021

Background

The incidence of multidrug-resistant tuberculosis (MDR-TB) remains critically high in countries of the former Soviet Union, where >20% of new cases and >50% of previously-treated cases have resistance to rifampin and isoniazid. Transmission of resistant strains, as opposed to resistance selected through inadequate treatment of drug-susceptible TB, is the main driver of incident MDR-TB in these countries.

Methods

We conducted a prospective, genomic analysis of all culture-positive TB cases diagnosed in 2018 and 2019 in the Republic of Moldova. We used phylogenetic methods to identify putative transmission clusters; spatial and demographic data were analyzed to further describe local transmission of M. tuberculosis.

Results

Of 2236 participants, 779 (36%) had MDR-TB, of whom 386 (50%) had never been treated previously for TB. 92% of MDR M. tuberculosis strains belonged to putative transmission clusters. Phylogenetic reconstruction identified three large clades that were comprised nearly uniformly of MDR-TB; two of these clades were of Beijing lineage and one of Ural lineage, and each had additional distinct clade-specific second-line drug resistance mutations and geographic distributions. Spatial and temporal proximity between pairs of cases within a cluster was associated with greater genomic similarity.

Conclusions

The MDR-TB epidemic in Moldova is the result of local transmission of multiple M. tuberculosis strains, including distinct clades of highly drug-resistant M. tuberculosis with varying geographic distributions and drug resistance profiles. This study demonstrates the role of comprehensive genomic surveillance for understanding the transmission of M. tuberculosis and highlights the urgency of interventions to interrupt transmission of highly drug-resistant M. tuberculosis.
SARS-CoV-2 and the role of vertical transmission from infected pregnant women to their fetuses: systematic review.
Authors: Pluddemann Annette , Spencer Elizabeth A , Heneghan Carl , Brassey Jon , Onakpoya Igho J , Rosca Elena Cecilia , Evans David H , Conly John M , Jefferson Tom
Published: July 2021

Background
Vertical transmission of SARS-CoV-2 has been reported but does not appear to be common. This study aims to systematically review the evidence for vertical transmission of SARS-CoV-2.
Methods
This review is part of an Open Evidence Review on the transmission dynamics of SARS-CoV-2 and the role of intrauterine mother to fetus transmission. Literature searches were performed in the WHO Covid-19 Database, LitCovid, medRxiv, and Google Scholar for SARS-CoV-2 using keywords and associated synonyms, search date up to 20 December 2020, no language restrictions.
Results
We included 106 studies assessing vertical transmission of SARS-CoV-2 from pregnant women to their neonates: these studies comprised 40 reviews (21 fulfilled systematic review methodology, including risk of bias assessment of included studies) and 66 primary studies including 32 case reports (of up to two cases) and 34 prospective and retrospective cohort studies, prospective and retrospective case series, observational studies (including asymptomatic screening), database studies and a quality improvement project. Almost all were conducted in a hospital setting. The 32 case reports were considered to be at high risk of bias, due to the study design; across the 34 remaining primary studies, risk of bias was low to moderate. Sixteen case reports examined vertical transmission, which was not related to maternal symptomatology. For the cohort and case series studies, the percentage of positive neonates ranged from 0% to 22% across the studies. Twenty studies reported no positive vertical transmission. Three studies that reported the highest positivity rates of 11%, 15% and 22% had specifically selected neonates with a positive test (within up to 35 days) within the study population and were therefore more selective populations. Across the cohort and case series studies there were 65/2391 (2.7%) neonates born to mothers with a diagnosis of COVID-19 tested positive for SARS-CoV-2 within 24 hours of birth. No evidence correlated maternal symptomatology to vertical transmission. Mode of delivery did not correlate with rates of vertical transmission. Of 25 studies, 7 identified SARS-CoV-2 in placental tissue; some of these did not demonstrate vertical transmission to the neonate. No study reported the results of viral culture to detect SARS-CoV-2.
Conclusions
The results of these studies indicate that vertical transmission is possible, but is not frequent, and factors that influence when vertical transmission occurs are unknown. Further studies using standardised methods to establish viral infection are needed to establish vertical transmission rates and to assess clinical and other conditions affecting transmission.