bluuebunny/crossref_metadata_2025 huggingface dataset:
A Multicenter Evaluation of Paradoxical Adipose Hyperplasia Following Cryolipolysis for Fat Reduction and Body Contouring: A Review of 8658 Cycles in 2114 Patients
Authors: Nikolis Andreas , Enright Kaitlyn M
Published: December 2020

Background

Paradoxical adipose hyperplasia (PAH) is a rare, moderate-to-severe adverse event associated with cryolipolysis (CoolSculpting, CS).

Objectives

The aim of this study was to describe the incidence, diagnosis, and treatment of PAH occurring after CS for nonsurgical fat reduction.

Methods

A multicenter evaluation of all patients who underwent CS treatment between January 2015 and December 2019 at 8 Canadian medical centers was conducted. Data abstracted included symptoms, management strategy, outcome, operator characteristics, device characteristics, patient characteristics, body region, and CS treatment details. Incidence of PAH was calculated based on the number of treatment cycles.

Results

Our findings revealed incidence rates between 0.05% and 0.39%, which are slightly higher than the manufacturer’s quoted rate of 0.025% (1 per 4000 cycles). Incidence rates at all sites were dramatically reduced by over 75% with the implementation of newer models of CS units. Of patients who developed PAH, 55% were male and 77.8% were of European ethnic origin. The majority of cases (76.9%) were associated with older models of CS units.

Conclusions

Development of PAH may be related to a combination of factors, including older models of CS units and applicators, as well as individual characteristics that predispose certain patients.

Level of Evidence: 4
FifBase: a comprehensive fertility-associated indicators factor database for domestic animals
Authors: Li Hao , Hou Junyao , Chen Ziyu , Zeng Jingyu , Ni Yu , Li Yayu , Xiao Xia , Zhou Yaqi , Zhang Ning , Long Deyu , Liu Hongfei , Yang Luyu , Bai Xinyue , Li Qun , Li Tongtong , Che Dongxue , Li Leijie , Wang Xiaodan , Zhang Peng , Liao Mingzhi
Published: December 2020

Fertility refers to the ability of animals to maintain reproductive function and give birth to offspring, which is an important indicator to measure the productivity of animals. Fertility is affected by many factors, among which environmental factors may also play key roles. During the past years, substantial research studies have been conducted to detect the factors related to fecundity, including genetic factors and environmental factors. However, the identified genes associated with fertility from countless previous studies are randomly dispersed in the literature, whereas some other novel fertility-related genes are needed to detect from omics-based datasets. Here, we constructed a fertility index factor database FifBase based on manually curated published literature and RNA-Seq datasets. During the construction of the literature group, we obtained 3301 articles related to fecundity for 13 species from PubMed, involving 2823 genes, which are related to 75 fecundity indicators or 47 environmental factors. Eventually, 1558 genes associated with fertility were filtered in 10 species, of which 1088 and 470 were from RNA-Seq datasets and text mining data, respectively, involving 2910 fertility-gene pairs and 58 fertility-environmental factors. All these data were cataloged into FifBase (http://www.nwsuaflmz.com/FifBase/), where the fertility-related factor information, including gene annotation and environmental factors, can be browsed, retrieved and downloaded with the user-friendly interface.
Distinct Disease Severity Between Children and Older Adults With Coronavirus Disease 2019 (COVID-19): Impacts of ACE2 Expression, Distribution, and Lung Progenitor Cells
Authors: Zhang Zhao , Guo Liyan , Huang Li , Zhang Che , Luo Ruibang , Zeng Liang , Liang Huiying , Li Qiuhui , Lu Xiaoxia , Wang Xianfeng , Ma Chui Yan , Shao Jianbo , Luo Weiren , Li Le , Liu Li , Li Ziyue , Zhou Xiaoya , Zhang Xiaoxian , Liu Jie , Yang Jinjuan , Kwan Ka Yi , Liu Wei , Xu Yi , Jiang Hua , Liu Hongsheng , Du Hui , Wu Yanheng , Yu Guangyin , Chen Junhui , Wu Jieying , Zhang Jinqiu , Liao Can , Chen Huanhuan Joyce , Chen Zhiwei , Tse Hung-fat , Xia Huimin , Lian Qizhou
Published: December 2020

Background

Children and older adults with coronavirus disease 2019 (COVID-19) display a distinct spectrum of disease severity yet the risk factors aren’t well understood. We sought to examine the expression pattern of angiotensin-converting enzyme 2 (ACE2), the cell-entry receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and the role of lung progenitor cells in children and older patients.

Methods

We retrospectively analyzed clinical features in a cohort of 299 patients with COVID-19. The expression and distribution of ACE2 and lung progenitor cells were systematically examined using a combination of public single-cell RNA-seq data sets, lung biopsies, and ex vivo infection of lung tissues with SARS-CoV-2 pseudovirus in children and older adults. We also followed up patients who had recovered from COVID-19.

Results

Compared with children, older patients (>50 years.) were more likely to develop into serious pneumonia with reduced lymphocytes and aberrant inflammatory response (P = .001). The expression level of ACE2 and lung progenitor cell markers were generally decreased in older patients. Notably, ACE2 positive cells were mainly distributed in the alveolar region, including SFTPC positive cells, but rarely in airway regions in the older adults (P < .01). The follow-up of discharged patients revealed a prolonged recovery from pneumonia in the older (P < .025).

Conclusions

Compared to children, ACE2 positive cells are generally decreased in older adults and mainly presented in the lower pulmonary tract. The lung progenitor cells are also decreased. These risk factors may impact disease severity and recovery from pneumonia caused by SARS-Cov-2 infection in older patients.
Rethinking the political economy of place: challenges of productivity and inclusion
Authors: Evenhuis Emil , Lee Neil , Martin Ron , Tyler Peter
Published: December 2020

The global financial crisis of just over a decade ago exposed longer-term systemic problems in global capitalism of which two of the most prominent are the slowdown in the underlying trend rate of productivity growth, alongside a rise in economic and spatial inequalities in many advanced economies. The Covid-19 pandemic looks set to further amplify these problems. This Editorial begins by discussing the scale of the productivity slowdown and of the widening inequalities that have emerged, particularly with regard to their spatial dimension: that is how the uneven and slow development of productivity and rise in inequalities have played out across and within regions and cities. It then briefly considers underlying factors that lie behind these trends, including financialisation / financial globalization, the diminishing role of organised labour, segmentation of the labour market favouring workers who play a key role in financialisation, together with the increasing polarisation within societies according to skill and, crucially, the impact of changing industrial composition particularly as it relates to the rise of the high-tech sectors. The Editorial then examines in what ways the slowdown of productivity and widening of economic and spatial inequalities, may be interrelated, and questions the notion of any efficiency-equity trade-off. Lastly, it considers whether the ‘inclusive growth’ agenda can potentially reconcile the two ambitions of improving productivity performance and lessening inequalities, reflecting on what inclusive growth could mean, and what it could imply in terms of policy. Thus far, it appears that an inclusive growth agenda has only gained some traction at the subnational level, which seems to reflect – at least in part – attempts by cities and regions to address gaps in policy left by national governments.
Taking the frozen elephant trunk technique to the next level by a stented side branch for a left subclavian artery connection: a feasibility study
Authors: Grabenwöger Martin , Mach Markus , Mächler Heinrich , Arnold Zsuzsanna , Pisarik Harald , Folkmann Sandra , Harrer Marie-Luise , Geisler Daniela , Moidl Reinhard , Winkler Bernhard , Bonatti Johannes , Czerny Martin , Weiss Gabriel
Published: December 2020

OBJECTIVES

Our goal was to develop a modified frozen elephant trunk (FET) prosthesis with a stented left subclavian artery (LSA) side branch for LSA connection and to perform preclinical testing in a human cadaver model.

METHODS

We measured aortic diameters, distance between and diameters of supra-aortic vessels and the distance from the LSA offspring to the level of the left vertebral artery offspring in 70 patients. Based on these measurements, a novel FET prosthesis was developed (Cryolife/Jotec, Hechingen, Germany) featuring a stented side branch for an intrathoracic LSA connection. The feasibility and ease of implantation were tested in 2 human cadaver models at the Anatomical Institute of the Medical University Graz. A covered stent graft (Advanta V12™ by Atrium Medical Corp., Hudson, NH, USA) was used for an LSA extension.

RESULTS

Accurate deployment of the novel FET prosthesis with anatomical orientation of the stented side branch towards the LSA ostium followed by consecutive stent graft deployment was feasible in both cases. Proximalizing the distal anastomosis level from zone 3 to zone 1 not only diminished the complexity of the procedure but substantially facilitated the completion of the distal anastomosis. A 2.5-cm long extension stent graft was sufficient to seal to the LSA and to maintain left vertebral artery patency in both cases.

CONCLUSIONS

This initial study in human anatomical bodies could demonstrate the feasibility of implanting a newly designed FET prosthesis. This evolution of the FET technique has the potential to substantially ease total aortic arch replacement by proximalization of the distal anastomosis into zone 1 and by shortening spinal and lower body hypothermic circulatory arrest times via a stented side branch to the LSA. This direct connection enables early restoration of systemic perfusion.
Health-related quality of life among rural adults with type 2 diabetes mellitus: a cross-sectional study
Authors: Kang Ning , Liu Xiaotian , Liao Wei , Tu Runqi , Sang Shengxiang , Zhai Zhihan , Hou Jian , Wang Chongjian , Wang Xiaoqiong , Li Yuqian
Published: December 2020

Background

Previous reports about health-related quality of life (HRQoL) of type 2 diabetes mellitus (T2DM) concentrated on general patients rather than patients in rural areas with poor infrastructure and limited resources. Thus, the aims of this study were to evaluate the HRQoL of diabetics in the countryside and explore its influencing factors.

Methods

A total of 23 053 participants aged from 18 to 79 years were drawn from the Henan Rural Cohort Study for this cross-sectional study. The HRQoL of participants were assessed by utility index and VAS-score of European Quality of Life Five Dimension Five Level Scale (EQ-5D-5L) instrument. Binary logistic regression, generalized linear and tobit regression models were used to estimate the potential influencing factors on HRQoL.

Results

This study (23 053 participants) included 2231 T2DM patients with a crude prevalence of 9.68%. The utility index and VAS-score in health group were 0.96 ± 0.10 and 78.85 ± 14.53, while in T2DM group were 0.93 ± 0.15 and 74.09 ± 16.09, respectively. In total, most diabetics reported problem about pain/discomfort dimension. Being old, poverty, low physical activity, and with comorbidities was negatively related to HRQoL of diabetics, while high educational level was positively related to HRQoL.

Conclusion

HRQoL of rural T2DM patients depended on several sociodemographic factors. More attention should be paid to diabetics with poor socioeconomic status in rural areas.

Clinical trial registration

The Henan Rural Cohort Study has been registered at Chinese Clinical Trial Register (Registration number: ChiCTR-OOC-15006699) http://www.chictr.org.cn/showproj.aspx?proj=11375.
Temperate forests respond in a non-linear way to a population gradient of wild deer
Authors: Ramirez J Ignacio , Jansen Patrick A , den Ouden Jan , Li Xuqing , Iacobelli Palma , Herdoiza Natalie , Poorter Lourens
Published: December 2020

Wild deer exert strong top–down control on forest composition by browsing on palatable trees, and these effects are exacerbated as red, fallow, and roe deer populations increase in northern temperate forests. However, the relationship between deer abundance and plant recruitment remains poorly documented. Here, we combined camera trap and vegetation plot data to quantify the shape of the relationship between habitat utilization by deer (red, fallow and roe deer) with different components of the forest understory in ten sites distributed across a temperate mixed forest in the Veluwe, the Netherlands. The list of forest attributes included the density, richness and diversity of saplings, the proportion of conifers to broadleaves, the number of browsed broadleaves and conifers, the forest basal area, the understory cover of shrubs, moss and bare soil and the depth of the litter layer. When applying General Linear Mixed Models to those camera trap data, six of the eleven forest variables were related to the utilization level (UL) by deer. With increasing UL by fallow deer, there was a decrease in sapling species richness (β = −0.26). With increasing UL by red deer, there was a decrease in litter depth (β = −0.14) and an increase in browsed broadleaf stems (β = 0.40). With increasing UL by roe deer, there was a decrease in species richness of sapling plants (β = −0.26), Shannon diversity (β = −0.11) and shrub cover (β = −0.36), whereas there was an increase in stem density (β = 0.06). When combining all deer species into one guild, a negative relation was found between UL by deer and sapling richness (β = −0.21), diversity (β = −0.09) and litter depth (β = −0.14) and a positive relation with sampling density (β = 0.04). The relationship between UL by deer and different forest attributes followed a linear log10 shape. When back transforming, the response was curvilinear with large changes at a low UL and small changes when the UL was high. Yet, the exact shape of the curve varied according to (a) biotic factors specific to each study location. The conservation of temperate forests can benefit from limiting the size of deer populations and the time deer spend browsing in forest patches with high biodiversity value.
Insights into How Spinosad Seed Treatment Protects Onion From Onion Maggot (Diptera: Anthomyiidae)
Authors: Moretti Erica A , Taylor Alan G , Wickings Kyle , Nault Brian A
Published: December 2020

Onion maggot, Delia antiqua (Meigen), is a serious pest of onion Allium cepa L. in northern temperate regions. Over the last decade, D. antiqua has been managed principally using a pesticide seed treatment package containing the reduced-risk insecticide spinosad. While spinosad protects onion seedlings from D. antiqua, very little is known regarding how protection occurs. The main objectives of this study were to assess susceptibility of 1- and 2-wk-old larvae to spinosad through two different modes of exposure: ingestion and contact, and to evaluate larval feeding behavior in choice and no-choice tests with onion seedlings grown from treated and untreated seeds. Results showed that spinosad was more than twice as lethal to 1-wk than 2-wk-old larvae when it was ingested, but was equally toxic to both larval ages via contact exposure. In choice assays, larvae preferred feeding on untreated plants; however, without a choice, larvae fed and survived equally well on untreated and treated plants, suggesting that spinosad may have a deterrent effect. In a field study, levels of spinosad within young onion plants and in the soil around roots were monitored in addition to the cumulative number of onion seedlings killed by D. antiqua. Spinosad was detected in the soil and in both aboveground and belowground plant tissue, indicating that spinosad translocates into foliage, but declines in plant tissue and soil as plant mortality from D. antiqua feeding increases. Together, these results provide valuable insight into how spinosad protects onion seedlings and reveal key areas in need of further investigation.
Parallel reaction pathways accelerate folding of a guanine quadruplex
Authors: Harkness Robert W , Hennecker Christopher , Grün J Tassilo , Blümler Anja , Heckel Alexander , Schwalbe Harald , Mittermaier Anthony K
Published: December 2020

G-quadruplexes (G4s) are four-stranded, guanine-rich nucleic acid structures that can influence a variety of biological processes such as the transcription and translation of genes and DNA replication. In many cases, a single G4-forming nucleic acid sequence can adopt multiple different folded conformations that interconvert on biologically relevant timescales, entropically stabilizing the folded state. The coexistence of different folded conformations also suggests that there are multiple pathways leading from the unfolded to the folded state ensembles, potentially modulating the folding rate and biological activity. We have developed an experimental method for quantifying the contributions of individual pathways to the folding of conformationally heterogeneous G4s that is based on mutagenesis, thermal hysteresis kinetic experiments and global analysis, and validated our results using photocaged kinetic NMR experiments. We studied the regulatory Pu22 G4 from the c-myc oncogene promoter, which adopts at least four distinct folded isomers. We found that the presence of four parallel pathways leads to a 2.5-fold acceleration in folding; that is, the effective folding rate from the unfolded to folded ensembles is 2.5 times as large as the rate constant for the fastest individual pathway. Since many G4 sequences can adopt many more than four isomers, folding accelerations of more than an order of magnitude are possible via this mechanism.
Human resources for health coordination mechanisms: lessons from Bauchi and Cross River states of Nigeria
Authors: Okech M , Okoroafor S C , Mohammed B , Ojo O
Published: December 2020

Background

Addressing the challenges of the health crisis requires collaboration by multiple sectors and stakeholders with a complementary role in a single platform that coordinates policy and programs relating to the health workforce for sustainability.

Methods

Information from purposefully selected stakeholders involved in human resources for health programs in two selected states of Nigeria was collected during a workshop attended by 60 participants drawn from government, multilateral agencies, the private sector, bilateral agencies, academia, professional associations, and regulatory bodies.

Results

Lessons learnt from Bauchi and Cross River states HRH platforms included successful joint planning and implementation human resources for health strategies that significantly mobilized resources and improved performance. Human resources for health coordination platforms with strong governance structures are sustainable.

Conclusion

The coordination platforms require governance structures for inter-sectoral coordination and collaboration. This enhances joint planning, implementation and monitoring of HRH activities.
The Massacre at Gracias a Dios: Mobility and Violence on the Lower Rio Grande, 1821–1856
Authors: Baumgartner Alice L
Published: December 2020

On March 20, 1856, Mexican forces massacred a band of Lipan Apaches at a river crossing known as Gracias a Dios. Historians have described the massacre as an example of the growing violence against Native peoples in Mexico, motivated by a desire to control movement across the U.S.-Mexico border. But given the long history of border crossings in the region, why did Mexican forces massacre the Lipan Apaches in 1856, rather than at some earlier point? The Lipan Apaches had long used the border to their advantage, forging alliances with Mexico in 1822, with the Republic of Texas in 1838, and again with Mexico in 1853. These alliances show that the Lipans were important to the history of the U.S.-Mexico borderlands not only because their raids wrought devastation, but also because they were geopolitical actors in their own right. To understand why Mexican forces turned on their Native allies, we must examine how the policies of neighboring nations interacted with—and shaped—one another. Convinced that Mexico’s Native allies were raiding their ranches with impunity, Texans decided to launch an expedition against the Lipans in Mexico in 1855. This attack made Mexico’s alliance with the Lipans into a liability rather than an advantage. The massacre that resulted shows that the shift toward greater violence against Native peoples was, at its core, a transnational process.
The latest in systemic lupus erythematosus-accelerated atherosclerosis: related mechanisms inform assessment and therapy
Authors: Appleton Brenna D. , Major Amy S.
Published: December 2020

Purpose of Review

Accelerated atherosclerosis is a significant comorbidity and the leading cause of death for patients with systemic lupus erythematosus (SLE). It is now apparent that SLE-accelerated atherosclerosis is not driven solely by traditional cardiovascular risk factors, adding complexity to disease characterization and mechanistic understanding. In this review, we will summarize new insights into SLE-accelerated atherosclerosis evaluation, treatment, and mechanism.

Recent findings

Recent work highlights the need to incorporate inflammatory biomarkers into cardiovascular disease (CVD) risk assessments. This is especially true for SLE patients, in which mechanisms of immune dysfunction likely drive CVD progression. There is new evidence that commonly prescribed SLE therapeutics hinder atherosclerosis development. This effect is achieved both by reducing SLE-associated inflammation and by directly improving measures of atherosclerosis, emphasizing the interconnected mechanisms of the two conditions.

SLE-accelerated atherosclerosis is most likely the consequence of chronic autoimmune inflammation. Therefore, diligent management of atherosclerosis requires assessment of SLE disease activity as well as traditional cardiovascular risk factors. This supports why many of the therapeutics classically used to control SLE also modulate atherosclerosis development. Greater understanding of the mechanisms underlying this condition will allow for the development of more targeted therapeutics and improved outcomes for SLE patients.
Update on the cellular pathogenesis of lupus
Authors: Gensous Noémie , Boizard-Moracchini Andrea , Lazaro Estibaliz , Richez Christophe , Blanco Patrick
Published: December 2020

Purpose of review

Aberrations in the innate and in the adaptive arms of the immune system play both important roles in the initiation and progression of systemic lupus erythematosus (SLE). The aim of this study was to provide an update on the most recent findings on the cellular pathogenesis of SLE. Our overview focused particularly on results obtained over the last 18 months.

Recent findings

Recent observations have provided an improved understanding of the importance of low-density granulocytes, a highly proinflammatory subset of neutrophils. We also highlighted in this work recent descriptions of the various cellular sources associated with the interferon signature. In addition, novel contributions have also developed our understanding of the potential importance of extrafollicular T–B-cell interactions in SLE pathogenesis. Finally, the role of recently described B and T-cell subsets, that is, atypical memory B cells, T-peripheral helper cells, and Th10 T cells, were also reviewed.

Recent findings in the cellular pathogenesis of SLE give a deeper comprehension of previously described mechanisms which drive SLE pathogenesis and shed light on novel players in immune dysregulation that could help to identify potential therapeutic targets.
Cellular aspects of the pathogenesis of lupus nephritis
Authors: Chang Anthony , Clark Marcus R. , Ko Kichul
Published: December 2020

Purpose of review

Lupus nephritis is a common severe manifestation of systemic lupus erythematosus. Despite recent advances in therapeutics and understanding of its pathogenesis, there are still substantial unmet needs. This review discusses recent discoveries in these areas, especially the role of tubulointerstitial inflammation (TII) in lupus nephritis.

Recent findings

Non-white ethnicity is still a major risk and poor prognostic factor in lupus nephritis. TII and fibrosis have been found to be associated with worse renal outcome but the current lupus nephritis treatment guidelines and trials are based on the degree of glomerular inflammation. In combination with mycophenolate mofetil, a B-cell-targeted therapy (belimumab) and a calcineurin inhibitor (voclosporin) have shown efficacy in recent lupus nephritis trials. However, response rates have been modest. While lupus glomerulonephritis results from immune complex deposition derived from systemic autoantibodies, TII arises from complex processes associated with in situ adaptive cell networks. These include local antibody production, and cognate or antigen-induced interactions between T follicular helper cells, and likely other T-cell populations, with antigen presenting cells including B cells, myeloid dendritic cells and plasmacytoid dendritic cells.

Better understanding of the pathogenesis of TII will identify novel therapeutic targets predicted to improve outcomes in our patients with lupus nephritis.
Double-negative T cells in autoimmune diseases
Authors: Li Hao , Tsokos George C.
Published: December 2020

Purpose of review

TCRαβ+CD4-CD8- double-negative T (DNT) cells, a principal subset of mature T lymphocytes, have been closely linked with autoimmune/inflammatory conditions. However, controversy persists regarding their ontogeny and function. Here, we present an overview on DNT cells in different autoimmune diseases to advance a deeper understanding of the contribution of this population to disease pathogenesis.

Recent findings

DNT cells have been characterized in various chronic inflammatory diseases and they have been proposed to display pathogenic or regulatory function. The tissue location of DNT cells and the effector cytokines they produce bespeak to their active involvement in chronic inflammatory diseases.

By producing various cytokines, expanded DNT cells in inflamed tissues contribute to the pathogenesis of a variety of autoimmune inflammatory diseases. However, it is unclear whether this population represents a stable lineage consisting of different subsets similar to CD4+ T helper cell subset. Better understanding of the possible heterogeneity and plasticity of DNT cells is needed to reveal interventional therapeutic opportunities.
Does aerobic exercise training alter responses to opioid analgesics in individuals with chronic low back pain? A randomized controlled trial
Authors: Bruehl Stephen , Burns John W. , Koltyn Kelli , Gupta Rajnish , Buvanendran Asokumar , Edwards David , Chont Melissa , Wu Yung Hsuan , Stone Amanda
Published: December 2020

We tested whether aerobic exercise training altered morphine analgesic responses or reduced morphine dosages necessary for adequate analgesia. Patients with chronic back pain were randomized to an 18-session aerobic exercise intervention (n = 38) or usual activity control (n = 45). Before and after the intervention, participants underwent 3 laboratory sessions (double-blinded, crossover) to assess effects of saline placebo, i.v. morphine (0.09 mg/kg), and i.v. naloxone (12 mg) on low back pain and evoked heat pain responses. Differences in evoked and back pain measures between the placebo and morphine conditions indexed morphine analgesia, with pre-post intervention changes the primary outcome. Endogenous opioid analgesia was indexed by differences in evoked and low back pain measures between the naloxone and placebo conditions. A Sex X Intervention interaction on the analgesic effects of morphine on visual analogue scale back pain intensity was observed (P = 0.046), with a similar trend for evoked pain threshold (P = 0.093). Male exercisers showed reduced morphine analgesia pre-post intervention, whereas male controls showed increased analgesia (with no differences in females). Of clinical significance were findings that relative to the control group, aerobic exercise produced analgesia more similar to that observed after receiving ≈7 mg morphine preintervention (P < 0.045). Greater pre-post intervention increases in endogenous opioid function (from any source) were significantly associated with larger pre-post intervention decreases in morphine analgesia (P < 0.046). The overall pattern of findings suggests that regular aerobic exercise has limited direct effects on morphine responsiveness, reducing morphine analgesia in males only.
Oral potentially malignant disorders: new insights for future treatment
Authors: Gurizzan Crisitna , Lorini Luigi , Bossi Paolo
Published: December 2020

Purpose of review

The purpose of this review is to define the issues regarding oral potentially malignant disorders (OPMDs) and provide an overview of currently available treatments and ongoing clinical trials for future opportunities.

Recent findings

Nowadays, the treatment of choice of OPMD is surgery, whose role in preventing malignant transformation is however limited because of the high rate of recurrence and field cancerization. There have been several attempts of combining systemic therapies with surgery to reduce risk of malignant transformation. The identification of biomarkers that could predict malignant transformation is crucial in better tailoring the risk profile and possible therapeutic approaches.

Loss of heterozygosity remains the most predictive marker of malignant transformation; however, role of specific microRNA and OPMD immune infiltration are emerging as potential biomarkers. Given the failure of previous trials with various chemopreventive strategies, new strategies should be defined to address the issue of systemic prevention of malignant transformation. Recent updates about immune infiltration and the immune-equilibrium concept for OPMD could shed light into new preventive approaches.
Pre-therapeutic Biomarkers for Ranibizumab Therapy among Type 2 Diabetic Patients with Diabetic Macular Edema
Authors: Paine Suman K. , Bhattacharjee Chandra K. , Bhaduri Gautam , Pramanik Subhasish , Borah Prasanta K. , Mahanta Jagadish , Basu Analabha , Mondal Lakshmi K.
Published: December 2020

SIGNIFICANCE

A differential outcome in randomized controlled trials of anti–vascular endothelial growth factor (anti-VEGF) therapy, including ranibizumab, for diabetic macular edema is a major dilemma for planning, optimizing, and managing clinical usage. The variable outcome of the therapeutics necessitates the importance of finding a predictive biomarker for anti-VEGF therapy to improve subject selection.

PURPOSE

Our study correlates the baseline pro- and anti-VEGF isoforms and its three receptors (VEGFReceptor1, VEGFReceptor2, and VEGFReceptor3) for circulatory candidate protein molecules among diabetic patients with macular edema, with the clinical outcome of ranibizumab therapy.

METHODS

This study included 86 individuals who were anti-VEGF naive at the time of ascertainment but have completed the standardized therapy regimen of the clinic. Plasma proteins for pro- and anti-VEGF isoforms and its three receptors were determined in replicate by an enzyme-linked immunosorbent assay.

RESULTS

The study demonstrated that 56 (65.12%) individuals benefited from the therapy in terms of letter gain (Snellen chart). Baseline plasma soluble VEGF receptor 2 (sVEGFR-2) was significantly higher among responders (65.10 pg/mL; 95% confidence interval, 55.41 to 74.80 pg/mL) compared with nonresponders (46.38 pg/mL; 95% confidence interval, 38.69 to 54.07 pg/mL; P
FDR = .03). Diffuse diabetic macular edema with proliferative diabetic retinopathy increases the risk of nonresponse to the therapy by 3.03-fold (P
FDR = .04).

CONCLUSIONS

The present study postulates that diffuse diabetic macular edema with proliferative diabetic retinopathy and baseline circulatory soluble VEGF receptor 2 may be potential candidates as therapy-stratifying markers for ranibizumab treatment among patients with diabetic macular edema.
Case Report: Successful Corneal Crosslinking in a Patient with Corneal Ectasia Associated with Stevens-Johnson Syndrome
Authors: Li Ye , Lu Lucy M. , Gokul Akilesh , Ziaei Mohammed
Published: December 2020

SIGNIFICANCE

Corneal ectasia can be a complication of Stevens-Johnson syndrome. When detected in a timely manner, corneal crosslinking can be a safe treatment. This is an important association to highlight that early diagnosis and treatment can prevent the need for invasive surgical procedures such as keratoplasty.

PURPOSE

This study aimed to report a successful accelerated epithelium-off corneal crosslinking in a rare case of corneal ectasia secondary to Stevens-Johnson syndrome.

CASE REPORT

A 25-year-old Indian man presented with a progressive visual acuity decline 5 years after an acute episode of Stevens-Johnson syndrome secondary to penicillin ingestion. Serial tomography scans confirmed the diagnosis of corneal ectasia. After the preparation of the ocular surface, which was deemed to have a mild degree of limbal stem cell deficiency, with frequent preservative-free lubrication and steroid use, accelerated epithelium-off crosslinking was performed with 4 minutes of continuous ultraviolet-A exposure at 30 mW/cm2 and a total energy dose of 7.2 J/cm2. Complete re-epithelialization was observed at 72 hours after crosslinking with no complications. Corneal tomography 15 months after treatment showed stabilization of ectasia, with improvement in visual acuity.

CONCLUSIONS

Corneal ectasia is a rare but important complication of Stevens-Johnson syndrome. Accelerated epithelium-off crosslinking treatment can be considered in patients with a compromised ocular surface after Stevens-Johnson syndrome. Pre-operative optimization of the ocular surface and vigilant monitoring in the early post-operative period are recommended for the prevention of complications.
Subjective Evaluation of Defocus and Astigmatism Combinations Using Image Simulation in Presbyopes
Authors: Vincent Marc , Marin Gildas , Legras Richard
Published: December 2020

SIGNIFICANCE

Image simulation is a useful and efficient tool to explore the impact of defocus and astigmatism combinations on visual acuity and image quality score when accommodation is taken into account.

PURPOSE

The goal of this experiment was to determine if a simulation is able to predict visual acuity and image quality score (IQS) with defocus and astigmatism combinations in presbyopes.

METHODS

We measured visual acuity and IQS in five defocus and astigmatism combinations in either real or simulated conditions. In real conditions, the subjects viewed a stimulus through an ophthalmic lens or a deformable mirror. In simulated conditions, subjects viewed images of the same stimulus with simulated blur. The amounts of defocus and astigmatism combinations of a progressive addition lens in near vision were generated through a static correction of the subject's aberrations. We simulated three levels of accommodation: subject could not accommodate (FOC0), subject could accommodate to the less hyperopic focal point (FOC1), or subject could accommodate to the circle of least confusion (FOC2).

RESULTS

Visual acuity or IQS did not differ between mirror and progressive addition lens conditions. Visual acuity measured in real blur conditions differed significantly from that in FOC0 simulated blur condition but were similar to that in FOC1 and FOC2 simulated blur conditions. Image quality score obtained in real conditions were between scores measured with the FOC0 and FOC1 simulated conditions, suggesting that the subjects were able to produce a low level of accommodation.

CONCLUSIONS

Accommodation may play a role when comparing optical and simulated defocus and astigmatism combinations. Presbyopic subjects are able to produce a low level of accommodation that may counterbalance a part of the deleterious effect of the astigmatism on image quality. Simulation remains a useful tool if the correct accommodation state is taken into account.
Uncorrected Refractive Error and Distance Visual Acuity in Children Aged 6 to 14 Years
Authors: Kleinstein Robert N. , Mutti Donald O. , Sinnott Loraine T. , Jones-Jordan Lisa A. , Cotter Susan A. , Manny Ruth E. , Twelker J. Daniel , Zadnik Karla ,   for the Collaborative Longitudinal Evaluation of Ethnicity and Refractive Error (CLEERE) Study Group
Published: December 2020

SIGNIFICANCE

This study presents the relationship between distance visual acuity and a range of uncorrected refractive errors, a complex association that is fundamental to clinical eye care and the identification of children needing refractive correction.

PURPOSE

This study aimed to analyze data from the Collaborative Longitudinal Evaluation of Ethnicity and Refractive Error Study to describe the relationship between distance uncorrected refractive error and visual acuity in children.

METHODS

Subjects were 2212 children (51.2% female) 6 to 14 years of age (mean ± standard deviation, 10.2 ± 2.1 years) participating in the Collaborative Longitudinal Evaluation of Ethnicity and Refractive Error Study between 2000 and 2010. Uncorrected distance visual acuity was measured using a high-contrast projected logMAR chart. Cycloplegic refractive error was measured using the Grand Seiko WR-5100K autorefractor. The ability of logMAR acuity to detect various categories of refractive error was examined using receiver operating characteristic curves.

RESULTS

Isoacuity curves show that increasing myopic spherical refractive errors, increasing astigmatic refractive errors, or a combination of both reduces distance visual acuity. Visual acuity was reduced by approximately 0.5 minutes of MAR per 0.30 to 0.40 D of spherical refractive error and by approximately 0.5 minutes of MAR per 0.60 to 0.90 D of astigmatism. Higher uncorrected hyperopic refractive error had little effect on distance visual acuity. Receiver operating characteristic curve analysis suggests that a logMAR distance acuity of 0.20 to 0.32 provides the best balance between sensitivity and specificity for detecting refractive errors other than hyperopia. Distance acuity alone was ineffective for detecting hyperopic refractive errors.

CONCLUSIONS

Higher myopic and/or astigmatic refractive errors were associated with predictable reductions in uncorrected distance visual acuity. The reduction in acuity per diopter of cylindrical error was about half that for spherical myopic error. Although distance acuity may be a useful adjunct to the detection of myopic spherocylindrical refractive errors, accommodation presumably prevents acuity from assisting in the detection of hyperopia. Alternate procedures need to be used to detect hyperopia.
A Randomized Trial of Objective Spectacle Prescriptions for Adults with Down Syndrome: Baseline Data and Methods
Authors: Anderson Heather A. , Benoit Julia S. , Marsack Jason D. , Manny Ruth E. , Ravikumar Ayeswarya , Fern Karen D. , Trast Kelsey R.
Published: December 2020

SIGNIFICANCE

It is difficult to determine the most efficacious refractive correction for individuals with Down syndrome using routine clinical techniques. New objective methods that optimize spectacle corrections for this population may reduce limitations on daily living by improving visual quality.

PURPOSE

This article describes the methods and baseline characteristics of study participants in a National Eye Institute–sponsored clinical trial to evaluate objectively derived spectacle corrections in adults with Down syndrome. Intersession repeatability of the primary outcome measure (distance visual acuity) is also reported.

METHODS

Adults with Down syndrome were enrolled into a nine-visit study to compare clinically derived spectacle corrections and two different objective spectacle corrections derived from wavefront aberration data. Spectacle corrections were randomized and dispensed for 2 months each. Distance visual acuity was measured with a Bailey-Lovie–style chart. Intersession repeatability of acuity was established by performing difference versus mean analysis from binocular acuity measures obtained through habitual corrections at visits 1 and 2.

RESULTS

Thirty adults (mean ± standard deviation age, 29 ± 10 years) with a large range of refractive errors were enrolled. Presenting visual acuity at visit 1 was reduced (right eye, 0.47 ± 0.20 logMAR; left eye, 0.42 ± 0.17 logMAR). The mean difference between visits 1 and 2 was 0.02 ± 0.06 logMAR, with a coefficient of repeatability (1.96 × within-subject standard deviation) of 0.12 logMAR.

CONCLUSIONS

This study seeks to investigate new strategies to determine optical corrections that may reduce commonly observed visual deficits in individuals with Down syndrome. The good intersession repeatability of acuity found in this study (six letters) indicates that, despite the presence of reduced acuity, adults with Down syndrome performed the outcome measure for this clinical trial reliably.
Targeting Uric Acid Prevents Brain Injury and Anxiety in a Rat Model of Hemorrhagic Shock
Authors: L’Ecuyer Sydnée , Gilbert Kim , Brochu Benjamin , Beyrouthy Joseph , Liu Chao , Bouchard Caroline , Gagné Marc-André , Khazoom François , Bernard Francis , Rousseau Guy , Charbonney Emmanuel
Published: December 2020

Secondary brain injury following hemorrhagic shock (HS) is a frequent complication in patients, even in the absence of direct brain trauma, leading to behavioral changes and more specifically anxiety and depression. Despite preclinical studies showing inflammation and apoptosis in the brain after HS, none have addressed the impact of circulating mediators. Our group demonstrated an increased uric acid (UA) circulation in rats following HS. Since UA is implicated in endothelial dysfunction and inflammatory response, we hypothesized UA could alter the blood–brain barrier (BBB) and impact the brain. Male Wistar rats were randomly assigned to: SHAM, HS (hemorrhagic shock) and HS + U (hemorrhagic shock + 1.5 mg/kg of uricase). The uricase intervention, specifically targeting UA, was administered during fluid resuscitation. It prevented BBB dysfunction (fluorescein sodium salt permeability and expression of intercellular adhesion molecule-1) following HS. As for neuroinflammation, all of the results obtained (MPO activity; Iba1 and GFAP expression) showed a significant increase after HS, also prevented by the uricase. The same pattern was observed after quantification of apoptosis (caspase-3 activity and TUNEL) and neurodegeneration (Fluoro-Jade). Finally, the forced swim, elevated plus maze, and social interaction tests detected anxiety-like behavior after HS, which was blunted in rats treated with the uricase. In conclusion, we have identified UA as a new circulatory inflammatory mediator, responsible for brain alterations and anxious behavior after HS in a murine model. The ability to target UA holds the potential of an adjunctive therapeutic solution to reduce brain dysfunction related to hemorrhagic shock in human.
Circulating Syndecan-1 and Tissue Factor Pathway Inhibitor, Biomarkers of Endothelial Dysfunction, Predict Mortality in Burn Patients
Authors: Keyloun John W. , Le Tuan D. , Pusateri Anthony E. , Ball Robert L. , Carney Bonnie C. , Orfeo Thomas , Brummel-Ziedins Kathleen E. , Bravo Maria C. , McLawhorn Melissa M. , Moffatt Lauren T. , Shupp Jeffrey W.
Published: December 2020

Objective:

The aim of this study is to evaluate the association between burn injury and admission plasma levels of Syndecan-1 (SDC-1) and Tissue Factor Pathway Inhibitor (TFPI), and their ability to predict 30-day mortality.

Background:

SDC-1 and TFPI are expressed by vascular endothelium and shed into the plasma as biomarkers of endothelial damage. Admission plasma biomarker levels have been associated with morbidity and mortality in trauma patients, but this has not been well characterized in burn patients.

Methods: This cohort study enrolled burn patients admitted to a regional burn center between 2013 and 2017. Blood samples were collected within 4 h of admission and plasma SDC-1 and TFPI were quantified by ELISA. Demographics and injury characteristics were collected prospectively. The primary outcome was 30-day in-hospital mortality.

Results:

Of 158 patients, 74 met inclusion criteria. Most patients were male with median age of 41.5 years and burn TBSA of 20.5%. The overall mortality rate was 20.3%. Admission SDC-1 and TFPI were significantly higher among deceased patients. Plasma SDC-1 >34 ng/mL was associated with a 32-times higher likelihood of mortality [OR: 32.65 (95% CI, 2.67–399.78); P = 0.006] and a strong predictor of mortality (area under the ROC [AUROC] 0.92). TFPI was associated with a nine-times higher likelihood of mortality [OR: 9.59 (95% CI, 1.02–89.75); P = 0.002] and a fair predictor of mortality (AUROC 0.68).

Conclusions:

SDC-1 and TFPI are associated with a higher risk of 30-day mortality. We propose the measurement of SDC-1 on admission to identify burn patients at high risk of mortality. However, further investigation with a larger sample size is warranted.
Low Microcirculatory Perfused Vessel Density and High Heterogeneity are Associated With Increased Intensity and Duration of Lactic Acidosis After Cardiac Surgery with Cardiopulmonary Bypass
Authors: Greenwood John C. , Jang David H. , Spelde Audrey E. , Gutsche Jacob T. , Horak Jiri , Acker Michael A. , Kilbaugh Todd J. , Shofer Frances S. , Augoustides John G.T. , Bakker Jan , Abella Benjamin S.
Published: December 2020

Introduction:

Lactic acidosis after cardiac surgery with cardiopulmonary bypass is common and associated with an increase in postoperative morbidity and mortality. A number of potential causes for an elevated lactate after cardiopulmonary bypass include cellular hypoxia, impaired tissue perfusion, ischemic-reperfusion injury, aerobic glycolysis, catecholamine infusions, and systemic inflammatory response after exposure to the artificial cardiopulmonary bypass circuit. Our goal was to examine the relationship between early abnormalities in microcirculatory convective blood flow and diffusive capacity and lactate kinetics during early resuscitation in the intensive care unit. We hypothesized that patients with impaired microcirculation after cardiac surgery would have a more severe postoperative hyperlactatemia, represented by the lactate time-integral of an arterial blood lactate concentration greater than 2.0 mmol/L.

Methods:

We measured sublingual microcirculation using incident darkfield video microscopy in 50 subjects on intensive care unit admission after cardiac surgery. Serial measurements of systemic hemodynamics, blood gas, lactate, and catecholamine infusions were recorded each hour for the first 6 h after surgery. Lactate area under the curve (AUC) was calculated over the first 6 h. The lactate AUC was compared between subjects with normal and low perfused vessel density (PVD < 18 mm/mm2), high microcirculatory heterogeneity index (MHI > 0.4), and low vessel-by-vessel microvascular flow index (MFIv < 2.6).

Results:

Thirteen (26%) patients had a low postoperative PVD, 20 patients (40%) had a high MHI, and 26 (52%) patients had a low MFIv. Patients with low perfused vessel density had higher lactate AUC compared with subjects with a normal PVD (22.3 [9.4–31.0] vs. 2.6 [0–8.8]; P < 0.0001). Patients with high microcirculatory heterogeneity had a higher lactate AUC compared with those with a normal MHI (2.5 [0.1–8.2] vs. 13.1 [3.7–31.1]; P < 0.001). We did not find a difference in lactate AUC when comparing high and low MFIv.

Conclusion:

Low perfused vessel density and high microcirculatory heterogeneity are associated with an increased intensity and duration of lactic acidosis after cardiac surgery with cardiopulmonary bypass.