Analyze of factors and prognosis of eyes lost to follow-up in retinal vein occlusive disease patients receiving anti-vascular endothelial growth factor therapy.

BACKGROUND: Patients with macular edema (ME) secondary to retinal vein occlusion (RVO) who received at least one intravitreal injection of anti-vascular endothelial growth factor therapy (VEGF) and lost to follow-up (LTFU) for more than six months were analyzed to investigate the factors contributing to the LTFU and the prognosis. METHOD: This was a retrospective, single-center study to analyze the causes and prognosis of LTFU over six months in RVO-ME patients treated with intravitreal anti-VEGF injections at our institution from January 2019 to August 2022 and to collect patients' baseline characteristics along with the number of injections before LTFU, primary disease, best corrected visual acuity (BCVA) before LTFU and after return visit, central macular thickness (CMT), months before LTFU and after LTFU, reasons for LTFU, and complications, to analyze the factors affecting visual outcome at a return visit. RESULTS: This study included 125 patients with LTFU; 103 remained LTFU after six months, and 22 returned after LTFU. The common reason for LTFU was "no improvement in vision" (34.4%), followed by "transport inconvenience" (22.4%), 16 patients (12.8%) were unwilling to visit the clinic, 15 patients (12.0%) had already elected to seek treatment elsewhere, 12 patients (9.6%) were not seen in time due to the 2019-nCov epidemic, and 11 patients (8.8%) cannot do it due to financial reasons. The number of injections before LTFU was a risk factor for LTFU (P < 0.05). LogMAR at the initial visit (P < 0.001), CMT at the initial visit (P < 0.05), CMT before the LTFU (P < 0.001), and CMT after the return visit (P < 0.05) were influential factors for logMAR at the return visit. CONCLUSION: Most RVO-ME patients were LTFU after anti-VEGF therapy. Long-term LTFU is greatly detrimental to the visual quality of patients; thus, the management of RVO-ME patients in follow-up should be considered.

COVID-19-associated lung microvascular endotheliopathy: a "from the bench" perspective

Rationale: Autopsy and biomarker studies suggest that endotheliopathy contributes to coronavirus disease (COVID-19)-associated acute respiratory distress syndrome. However, the effects of COVID-19 on the lung endothelium are not well defined. We hypothesized that the lung endotheliopathy of COVID-19 is caused by circulating host factors and direct endothelial infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Objectives: We aimed to determine the effects of SARS-CoV-2 or sera from patients with COVID-19 on the permeability and inflammatory activation of lung microvascular endothelial cells. Methods: Human lung microvascular endothelial cells were treated with live SARS-CoV-2;inactivated viral particles;or sera from patients with COVID-19, patients without COVID-19, and healthy volunteers. Permeability was determined by measuring transendothelial resistance to electrical current flow, where decreased resistance signifies increased permeability. Inflammatory mediators were quantified in culture supernatants. Endothelial biomarkers were quantified in patient sera. Measurements and Main Results: Viral PCR confirmed that SARS-CoV-2 enters and replicates in endothelial cells. Live SARS-CoV-2, but not dead virus or spike protein, induces endothelial permeability and secretion of plasminogen activator inhibitor 1 and vascular endothelial growth factor. There was substantial variability in the effects of SARS-CoV-2 on endothelial cells from different donors. Sera from patients with COVID-19 induced endothelial permeability, which correlated with disease severity. Serum levels of endothelial activation and injury biomarkers were increased in patients with COVID-19 and correlated with severity of illness. Conclusions: SARS-CoV-2 infects and dysregulates endothelial cell functions. Circulating factors in patients with COVID-19 also induce endothelial cell dysfunction. Our data point to roles for both systemic factors acting on lung endothelial cells and viral infection of endothelial cells in COVID-19-associated endotheliopathy.

Controversies and Disparities in the Management of Age-Related Macular Degeneration.

Age-related macular degeneration is a leading cause of blindness in patients aged 50 years and older. Prior to the 21st century, there were no effective treatments for this devastating disease. However, the last 20 years have heralded the development of treatments for both the nonexudative and exudative forms. The invention of AREDS vitamin supplements and anti-VEGF therapies forever changed the treatment of dry and wet age-related macular degeneration, respectively. The rapid adoption and expansion of these vision preserving treatments has created controversy regarding their cost, burden of administration, development, and use of new technologies, genetic considerations, and observed societal disparities. Many of these controversies and disparities persist today and will require further research to resolve.

Patient Perspective on the Monitoring of Their Wet Age-Related Macular Degeneration during Coronavirus Disease 2019: A Retrospective Study.

Background and Objectives: The purpose was to provide the patients' perspective on the monitoring of their wet age-related macular degeneration (wet AMD) during coronavirus disease 2019 (COVID-19) and the importance of telemedicine. Materials and Methods: Wet AMD patients that underwent intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections in two Swiss ophthalmology clinics, completed two questionnaires after the first confinement due to COVID-19 in Switzerland. The first evaluated their views concerning their adherence to scheduled injections during the confinement, and the application of telemedicine in the future. The second, adapted from the National Eye Institute Visual Function Questionnaire-25, assessed their opinions on visual function change during confinement. Results: From a total of 130 patients, 8.5% responded they did not respect their assigned schedule (group 1) while 91.5% responded they did (group 2). A total of 78.7% of group 2 considered treatment reception as more relevant compared to the risk of COVID-19 contraction. During the pre-lockdown period, group 2 patients required more help from others than group 1 patients (p = 0.02). In the possibility of another lockdown, 36.3% of group 1 and 8.7% of group 2 would choose telemedicine to monitor their wet AMD (p = 0.02), 54.5% and 86.9% would rather visit the clinic (p = 0.02), while 9.0% and 4.3% would cancel their appointment, respectively. It was found that 70% of group 1 and 33.6% of group 2 would prefer to use the telemedicine services than visiting a telemedicine centre (p = 0.04). Conclusions: During circumstances similar to the COVID-19 confinement, most patients would prefer to visit the clinic. Group 1 would prefer wet AMD monitoring via telemedicine at a higher rate than group 2.

Outcome of Patients Treated by Intravitreal Injections During the COVID-19 Lockdown: An Institutional Experience.

PURPOSE: To determine the loss of follow-up ratio and reasons during the COVID-19 lockdown in patients with retinal diseases treated by anti-vascular endothelial growth factor intravitreal injections and to report the visual outcome and rate of complications of these patients 1 year after the end of the lockdown. METHODS: This is a prospective descriptive cohort study (NCT04395859) conducted at the Rothschild Foundation Hospital - Paris between April 2020 and May 2021. Patients with retinal diseases treated by repeated intravitreal anti-VEGF injections (IVI) since before October 2019 were included. They filled-out a questionnaire and were followed up during a period of 1 year. RESULTS: During the COVID-19 lockdown 198 eyes (82.5%) of 157 patients (82.6%) received their injections in a timely manner (group 1) while 42 eyes (17.5%) of 33 patients (17.4%) had their injections delayed or missed (group 2). No statistically significant difference was found between group 1 and group 2 when comparing the change of mean best corrected distance visual acuity (BCVA) between month 12 and inclusion (p = 0.6) and the rate of ocular complications. The most frequent reasons for missing scheduled injections are appointments cancellation by the hospital (12 patients, 36%), fear of virus exposure during transportation (7 patients, 21%) or at the hospital (5 patients, 15%). Eighty-four percent (130/157 patients) of patients who attended their appointment were satisfied by the protective measures used in the hospital. CONCLUSION: COVID-19 lockdown did not seem to negatively affect the 1-year outcome of patients with retinal diseases treated by anti-VEGF IVIs who missed their scheduled injections. The BCVA and rate of complications at 1 year did not differ whether patients missed their scheduled injections or not. Maintaining IVIs during lockdown periods and educating patients about the risks of missing injections are pivotal in improving prognosis of retinal diseases.

Levels of Vascular Endothelial Growth Factor and Its Association with Pulmonary Embolism in COVID-19.

Coronavirus disease 2019 (COVID-19) is associated with pulmonary embolism, a condition mechanistically related to vascular endothelial growth factor (VEGF). Our objective was to identify whether VEGF levels, measured at hospital admission, may predict the occurrence of pulmonary embolism (and other thrombosis) during hospitalization. Of a total of 139 patients included in the study, a pulmonary embolism occurred in 4%, other thrombosis in 16%, and 80% remained thrombus free. Clinical and laboratory data at admission were similar among groups. VEGF levels were elevated in COVID-19 patients compared with 38 healthy controls (50.7 versus 15.0 pg/mL; P < 0.001), with an area under the receiver operating characteristic curve of 0.776. At a cutoff point >15.7 pg/mL, VEGF showed 64.7% sensitivity, 92.1% specificity, and a positive likelihood ratio of 8.2 to discriminate COVID-19. In COVID-19, VEGF levels were not different in patients with pulmonary embolism, other thrombosis, and thrombus-free patients (15.0 versus 84.0 versus 48.5 pg/mL, respectively; P = 0.19). VEGF correlated with C-reactive protein (ρ = 0.25), fibrinogen (ρ = 0.28), ferritin (ρ = 0.18), and the neutrophil-to-lymphocyte ratio (ρ = 0.20). Our study showed that VEGF is elevated in sera from patients with COVID-19 on arrival at the hospital and its levels correlate with inflammatory markers, although they are unable to predict the appearance of pulmonary embolism during hospitalization.

A review on post-COVID-19 pulmonary fibrosis and the role of nintedanib in its management

[...]the current evidence is limited and more evidence is awaited from the ongoing randomized clinical trials evaluating the safety and efficacy of nintedanib in the management of post-COVID-19 pulmonary fibrosis. Angiotensin II (1-10 amino acid long) has a number of profibrotic effects on lung parenchymal cells such as the induction of growth factors like TGF-ß1 for mesenchymal cells, ECM molecules, cytokines like IL-1, and increased motility of lung fibroblasts. [22] Antifibrotic Agent-Nintedanib Nintedanib, an indolinone derivative, also known by its developmental code BIBF1120, is a small molecule inhibitor of receptor tyrosine kinase of fibroblast growth factor receptor (FGFR)-1, platelet derived growth factor receptor (PDGFR)-a and ß, and vascular endothelial growth factor receptor (VEGFR-2). [29] Therefore, it appears that nintedanib by inhibiting the receptor tyrosine kinase of all the above mentioned growth factors is shown to have an effect in the treatment of idiopathic pulmonary fibrosis.

Alterations in heparan sulfate proteoglycan synthesis and sulfation and the impact on vascular endothelial function.

The glycocalyx attached to the apical surface of vascular endothelial cells is a rich network of proteoglycans, glycosaminoglycans, and glycoproteins with instrumental roles in vascular homeostasis. Given their molecular complexity and ability to interact with the intra- and extracellular environment, heparan sulfate proteoglycans uniquely contribute to the glycocalyx's role in regulating endothelial permeability, mechanosignaling, and ligand recognition by cognate cell surface receptors. Much attention has recently been devoted to the enzymatic shedding of heparan sulfate proteoglycans from the endothelial glycocalyx and its impact on vascular function. However, other molecular modifications to heparan sulfate proteoglycans are possible and may have equal or complementary clinical significance. In this narrative review, we focus on putative mechanisms driving non-proteolytic changes in heparan sulfate proteoglycan expression and alterations in the sulfation of heparan sulfate side chains within the endothelial glycocalyx. We then discuss how these specific changes to the endothelial glycocalyx impact endothelial cell function and highlight therapeutic strategies to target or potentially reverse these pathologic changes.

Effects of COVID-19 on Intravitreal Injection Clinic After Lockdown.

Purpose: To examine the return of patients to intravitreal injection clinic after the COVID-19 lockdown. Patients and Methods: The electronic medical records of all patients who received intravitreal injections at a tertiary care Veterans Health Administration (VHA) clinic 14 weeks post-lockdown (5/9/20-8/13/20) in Los Angeles County were reviewed. Reference groups included injection patients during the 7-week COVID-19 lockdown (3/19/20-5/8/20) and a 7-week pre-pandemic period in 2019 (3/19/19-5/8/19). Clinic volume was compared using a one-way ANOVA. Demographic data, medical and psychiatric co-morbidities, injection diagnoses, visual acuities, and clinic volumes were compared between the 3 periods using a generalized estimating equation multivariate analysis. Results: The post-lockdown period group averaged 25.1 visits per week, compared with 12.3/week during lockdown and 25.4/week pre-COVID in intravitreal injection clinic. In the post-lockdown period, the VHA injection clinic returned closer to the pre-lockdown volume compared to the VHA comprehensive clinic (98.9% vs 57.4%, p < 0.001). Post-lockdown, COPD patients and organ transplant patients were less likely to receive injections compared to 2019 (OR 0.76 p = 0.008, OR 1.37 p < 0.0001, respectively). Patients with a diagnosis of cancer increased in proportion between the pre-pandemic and the post-lockdown periods (OR 1.31, p = 0.007). No differences were found, according to psychiatric co-morbidities. After lockdown, the proportion of patients receiving injections for diabetic macular edema (DME) increased (OR 1.11, p = 0.01). Conclusion: Injection volume returned to pre-pandemic levels immediately after lockdown ended. However, patients with high-risk comorbidities did not return to intravitreal injection clinic post-lockdown. These results can inform medical organizations, which groups may need increased safety measures and targeted outreach to address their ophthalmic needs.

Consecutive central and branch retinal vein occlusions in the same eye of a young healthy COVID-19 patient: A unique case report.

Purpose: To report a case of consecutive central retinal vein occlusion (CRVO) and branch retinal vein occlusion (BRVO) in the same eye correlated with coronavirus disease (COVID-19) of the otherwise healthy patient. Observations: A 39-year-old woman with the diagnosis of COVID-19 infection for two weeks presented with a nonischemic central retinal vein occlusion (CRVO) in her right eye. The patient was on low-dose aspirin for anticoagulant prophylaxis (100 mg/day) for a week when the CRVO occurred. She had no history of any systemic risk factors for retinal vein occlusion (RVO) and her systemic evaluation failed to identify an etiology for her unilateral CRVO. While she was on monthly follow-up with no additional treatment, she experienced sudden visual acuity decrease in the same eye four months after the first RVO incident and one month after the cessation of aspirin intake. Her best corrected visual acuity (BCVA) was decreased from 20/25+ to 20/63. Her fundoscopic examination revealed increased intraretinal hemorrhages, dilated tortuous veins in the upper hemifield and macular edema. The central macular thickness measurement by optic coherence tomography was increased from 234 µm to 700 µm. The patient refused to undergo a fundus fluorescein angiography. After the diagnosis of the branch retinal vein occlusion with cystoid macular edema was done, the aspirin prophylaxis was restarted, and she received three intravitreal antivascular endothelial growth factor one month apart for her macular edema. Her BCVA improved to 20/20, and macular edema disappeared without any recurrence during the 6-month follow-up. Conclusions and importance: To the best of our knowledge, this unique case is the first report of consecutive RVOs in the same eye of a healthy young patient associated with COVID-19. As our case report demonstrated, close follow-up and timely initiation of appropriate treatment could give rise to complete resolution of RVO.

Impact of the COVID-19 pandemic on visual outcomes of diabetic macular edema patients at a tertiary care veterans affairs center.

Purpose: There are limited studies on factors that impacted retina clinic patient outcomes during the COVID-19 pandemic. We aimed to evaluate visual and anatomic outcomes in patients with diabetic macular edema (DME) requiring anti-VEGF injections at the veterans' affairs tertiary care eye clinic in Houston, TX. Methods: Patient volume from April 2020 was compared to that of April 2019 to determine attendance changes. To evaluate outcomes, we reviewed patients with DME who had scheduled appointments during April 2020. We tracked changes in central foveal thickness (CFT) and Snellen visual acuity (VA) measurements. Patient outcomes were classified as poor (defined as worsening VA or CFT at follow-up) or good (no worsening of either at follow-up). Regression analysis identified characteristics associated with poor outcomes. Results: To prevent the spread of COVID-19, patients were called to reschedule clinic appointments. Attendance frequency decreased from 523 patients in April 2019 to 246 patients in April 2020. 134 patients met inclusion criteria (mean age of 64.7 ± 8.8 years). 19/134 of patients were seen on schedule, 89/134 had delayed appointments (average follow-up interval of 115.2 ± 50.0 days), and 26/134 were lost to follow-up. Patients with delayed appointments had higher odds of poor outcome at follow-up compared to patients seen on schedule (OR = 4.03, 95% CI: 1.14-16.92, p = 0.04). Patient's baseline visual acuity, macular thickness, comorbidities, and diabetic retinopathy severity, and demographics did not affect visual outcome at follow-up. Conclusions: On average, patients were rescheduled to a visit 2.4 months later than their usual visit. Over half these patients experienced worsening of vision or edema. This demonstrates that lapses in care result in worsening of DME. However, there is no clear association between baseline characteristics and risk of disease progression. Supplementary Information: The online version contains supplementary material available at 10.1007/s40200-022-01049-5.

The importance of monitoring wet age-related macular degeneration patients during Coronavirus disease 19 pandemic: A retrospective study of assessment of functional and structural outcomes.

OBJECTIVES: Intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections are the gold standard treatment for wet age-related macular degeneration (wet AMD). Coronavirus disease 2019 (COVID-19) has led to the cancellation of many scheduled intravitreal anti-VEGF injection visits. We compared the functional and structural visual outcomes of wet AMD patients who did not adhere to their planned intervals (group 1) with those who did (group 2). METHODS: Wet AMD patients of Swiss Visio Montchoisi and RétinElysée were included. Best-corrected visual acuity (BCVA) and optical coherence tomography (OCT) changes between their first visit after the end of the first national lockdown in Switzerland (27 April 2020, first post-lockdown visit) and their last visit before the beginning of the first national lockdown in Switzerland (13 March 2020, last pre-lockdown visit) were assessed. The BCVA outcome was defined as unfavorable when there was a loss of≥5 ETDRS letters in the first post-lockdown visit compared to the BCVA at last pre-lockdown visit. The OCT outcome was defined as unfavorable when there was an increase in at least one of the parameters, intraretinal fluid (IRF), subretinal fluid (SRF), or pigment epithelial detachment (PED), at the first post-lockdown visit compared to the last pre-lockdown visit. MAIN RESULTS: Group 1 (89 patients, 109 eyes) had a 13.41% greater rate of unfavorable BCVA outcomes and a 38.27% greater rate of unfavorable OCT outcomes than group 2 (96 patients, 122 eyes) (P=0.04, P<0.0001, respectively). Multivariate analysis showed that the more the patients deviated from their programmed injections and the higher the BCVA pre-lockdown, the higher the rate of unfavorable BCVA outcomes (P=0.03 and P=0.02, respectively). OCT outcomes were not a predictive factor for an unfavorable BCVA outcome. CONCLUSIONS: The cancellation of many intravitreal anti-VEGF injection appointments resulted in worse functional and structural outcomes in wet AMD patients. The COVID-19 pandemic led many patients to refrain from their routine intravitreal anti-VEGF injection appointments, allowing us to analyze the role of designated intervals in the treatment of wet AMD. During any future lockdown due to COVID-19 or similar circumstances, continuity of care for wet AMD patients should be maintained.

First person – Aikta Sharma

First Person is a series of interviews with the first authors of a selection of papers published in Disease Models & Mechanisms, helping early-career researchers promote themselves alongside their papers. Aikta Sharma is first author on ‘Multiscale molecular profiling of pathological bone resolves sexually dimorphic control of extracellular matrix composition’, published in DMM. Aikta is a PhD student in the lab of Dr Claire E. Clarkin at the University of Southampton, Southampton, UK, investigating the role of osteoblast-derived vascular endothelial growth factor in bone matrix formation.

Long-term impact of delayed follow-up due to COVID-19 lockdown on patients with neovascular age-related macular degeneration.

BACKGROUND: During the first wave of the coronavirus disease 2019 (COVID-19) pandemic in 2020 outpatient care of neovascular age-related macular degeneration (nAMD) patients was severely reduced due to lockdown. Missed visits are known to be detrimental to patients in need of continued anti-vascular endothelial growth factor (VEGF) intravitreal injections (IVIs). The purpose of the study was to assess the effect of a month-long pause of regular visits and anti-VEGF IVIs in nAMD patients. METHODS: A retrospective study was performed. Patients were treated in a pro re nata ("as needed") scheme. Distance (logMAR) and near (logRAD) visual acuity (VA), optical coherence tomography, delay between planned and actual visit date and the indication for IVI were assessed for 3 continous visits in the 6 months before lockdown (V-3, -2, -1) and the 2 visits after lockdown (V0, V + 1). For analysis of long-term impact, records for visits 1 years before and after lockdown (V-3, V + 2) were gathered. RESULTS: We included 166 patients (120 female, 46 male) with a median (range) age of 80.88 (59.8-99.36) years. Compared to V-1, distance VA was significantly worse at both V0 (0.27 ± 0.21 vs 0.31 ± 0.23 logMAR, p < 0.001) and V + 1 (0.27 ± 0.21 vs 0.30 ± 0.23 logMAR, p = 0.021). Near VA was significantly worse at both V0 (0.31 ± 0.21 vs 0.34 ± 0.22 logRAD, p = 0.037) and V + 1 (0.31 ± 0.21 vs 0.34 ± 0.22 logRAD, p = 0.02). Visit delay (VD) at V0 was significantly longer than at V + 1 (30.81 ± 20.44 vs 2.02 ± 6.79 days, p < 0.0001). Linear regression analysis showed a significant association between visit delay and a reduction of near VA between V-1 and V + 1 (p = 0.0223). There was a significant loss of distance VA (p = 0.02) in the year after the lockdown period (n = 125) compared to the year before. Loss of reading acuity was not significantly increased (p = 0.3). One year post lockdown, there was no correlation between VA change and visit delay after lockdown (p > 0.05). CONCLUSIONS: In nAMD patients whose visits and treatment were paused for a month during the first wave of the COVID-19 pandemic, we found a loss of VA immediately after lockdown, which persisted during follow-up despite re-established anti-VEGF treatment. In the short term, length of delay was predictive for loss of reading VA. The comparison of development of VA during the year before and after the lockdown showed a progression of nAMD related VA loss which may have been accelerated by the disruption of regular visits and treatment. TRIAL REGISTRATION: This article does not report the outcome of a health care intervention. This retrospective study was therefore not registered in a clinical trials database.

Impact of the COVID-19 pandemic on patients receiving intravitreal injections

We analyzed the economic benefits versus safety risks of sharing anti-vascular endothelial growth factor (VEGF) vials during the coronavirus disease (COVID-19) pandemic. This single-center retrospective study analyzed the data of patients with neovascular age-related macular degeneration (nAMD), proliferative diabetic retinopathy (PDR) and retinal vein occlusion (RVO) who received anti-VEGF between January 2016 and July 2021 at Renmin Hospital, Wuhan University, China. Costs were compared of the two protocols of intravitreal injections (IVIs) of ranibizumab, aflibercept and conbercept after (i) splitting the vial content for use in two patients and after (ii) disposal of the remaining vial content after use in a single patient, with the COVID-19 outbreak considered as the demarcation point. The incidence rates of post-injection endophthalmitis (PIE) preand post-outbreak were analyzed. The mean cost of a single IVI increased by 33.3%, from 3917.67±71.69 to 5222.67±84.98 Chinese Yuan during the pandemic. The incidences of IVI-related culture-positive PIE were 0.0134% (3 in 22448) and 0.0223% (1 in 4479), respectively, before and after the pandemic (P=0.6532). We conclude that vial sharing of IVIs in a large clinical institution is not associated with increased PIE risk and can significantly reduce the cost of therapy. © 2022

A Review of Apta-POF-Sensors: The Successful Coupling between Aptamers and Plastic Optical Fibers for Biosensing Applications

Aptamers represent the next frontier as biorecognition elements in biosensors thanks to a smaller size and lower molecular weight with respect to antibodies, more structural flexibility with the possibility to be regenerated, reduced batch-to-batch variation, and a potentially lower cost. Their high specificity and small size are particularly interesting for their application in optical biosensors since the perturbation of the evanescent field are low. Apart from the conventional plasmonic optical sensors, platforms based on silica and plastic optical fibers represent an interesting class of devices for point-of-care testing (POCT) in different applications. The first example of the coupling between aptamers and silica optical fibers was reported by Pollet in 2009 for the detection of IgE molecules. Six years later, the first example was published using a plastic optical fiber (POF) for the detection of Vascular Endothelial Growth Factor (VEGF). The excellent flexibility, great numerical aperture, and the large diameter make POFs extremely promising to be coupled to aptamers for the development of a sensitive platform easily integrable in portable, small-size, and simple devices. Starting from silica fiber-based surface plasmon resonance devices, here, a focus on significant biological applications based on aptamers, combined with plasmonic-POF probes, is reported.

Depletion of γδ T Cells Leads to Reduced Angiogenesis and Increased Infiltration of Inflammatory M1-like Macrophages in Ischemic Muscle Tissue

γδ T cells, a small subset of T cells in blood, play a substantial role in influencing immunoregulatory and inflammatory processes. The functional impact of γδ T cells on angiogenesis in ischemic muscle tissue has never been reported and is the topic of the present work. Femoral artery ligation (FAL) was used to induce angiogenesis in the lower leg of γδ T cell depleted mice and wildtype and isotype antibody-treated control groups. Gastrocnemius muscle tissue was harvested 3 and 7 days after FAL and assessed using (immuno-)histological analyses. Hematoxylin and Eosin staining showed an increased area of tissue damage in γδ T cell depleted mice 7 days after FAL. Impaired angiogenesis was demonstrated by lower capillary to muscle fiber ratio and decreased number of proliferating endothelial cells (CD31+/BrdU+). γδ T cell depleted mice showed an increased number of total leukocytes (CD45+), neutrophils (MPO+) and neutrophil extracellular traps (NETs) (MPO+/CitH3+), without changes in the neutrophils to NETs ratio. Moreover, the depletion resulted in a higher macrophage count (DAPI/CD68+) caused by an increase in inflammatory M1-like macrophages (CD68+/MRC1−). Altogether, we show that depletion of γδ T cells leads to increased accumulation of leukocytes and M1-like macrophages, along with impaired angiogenesis.

Assessing Molecular Regulation of Vascular Permeability Using a VEGF-Inducible Zebrafish Model.

Vascular endothelial growth factor (VEGF) stimulates vascular permeability in a variety of human pathologies, such as cancer, ischemic stroke, cardiovascular disease, retinal conditions, and COVID-19-associated pulmonary edema, sepsis, acute lung injury, and acute respiratory distress syndrome. Comprehensive investigation of the molecular mechanisms of VEGF-induced vascular permeability has been hindered by the lack of in vivo models that easily facilitate genetic manipulation studies in real time. To address this need, we generated a heat-inducible VEGF transgenic zebrafish model of vascular permeability. Here, we describe how this zebrafish model can be used to monitor VEGF-induced vascular permeability through live in vivo imaging to identify genetic regulators that play key roles in vascular barrier integrity in physiological conditions and human disease processes.

Foramen magnum meningioma presented as cervical myelopathy in a pregnant COVID-19 patient: A case report.

Introduction: Meningioma is the second most common primary brain tumor. There are approximately 5.6 cases of meningioma per 100,000 pregnant women. Foramen magnum meningioma is rare, and the diagnosis, treatment, and prognosis are complex in pregnant women. Case presentation: Herein, we report a case of foramen magnum meningioma in a pregnant woman at 32 weeks of gestation, who presented with chronic neck pain and cervical myelopathy. She tested positive for COVID-19 infection. Magnetic resonance imaging findings were compatible with foramen magnum meningioma, and the pathologic analysis revealed a WHO grade-I meningioma. The patient underwent cesarean section followed by tumor excision due to fetal distress and rapid deterioration. Clinical discussion: Management of meningioma during pregnancy requires a multidisciplinary approach. No guidelines for surgical intervention, timing of pregnancy termination, or mode of delivery for pregnant patients with foramen magnum meningioma have been established. While it is best to prolong the pregnancy for as long as possible, a cesarean delivery is preferred to avoid increased intracranial pressure. Operative management of meningioma is warranted if the tumor is growing or symptomatic. This patient died due to the added complication of COVID-19. Although the prognosis of foramen magnum meningioma is usually favorable, COVID-19 comorbidity can increase illness severity. Conclusion: Maternal and fetal health status must be evaluated to decide whether surgical excision and pregnancy termination are needed. In this case, COVID-19 infection and meningioma disease course required further investigation.

State-of-the-art review of advanced electrospun nanofiber yarn-based textiles for biomedical applications.

The pandemic of the coronavirus disease 2019 (COVID-19) has made biotextiles, including face masks and protective clothing, quite familiar in our daily lives. Biotextiles are one broad category of textile products that are beyond our imagination. Currently, biotextiles have been routinely utilized in various biomedical fields, like daily protection, wound healing, tissue regeneration, drug delivery, and sensing, to improve the health and medical conditions of individuals. However, these biotextiles are commonly manufactured with fibers with diameters on the micrometer scale (> 10 µm). Recently, nanofibrous materials have aroused extensive attention in the fields of fiber science and textile engineering because the fibers with nanoscale diameters exhibited obviously superior performances, such as size and surface/interface effects as well as optical, electrical, mechanical, and biological properties, compared to microfibers. A combination of innovative electrospinning techniques and traditional textile-forming strategies opens a new window for the generation of nanofibrous biotextiles to renew and update traditional microfibrous biotextiles. In the last two decades, the conventional electrospinning device has been widely modified to generate nanofiber yarns (NYs) with the fiber diameters less than 1000 nm. The electrospun NYs can be further employed as the primary processing unit for manufacturing a new generation of nano-textiles using various textile-forming strategies. In this review, starting from the basic information of conventional electrospinning techniques, we summarize the innovative electrospinning strategies for NY fabrication and critically discuss their advantages and limitations. This review further covers the progress in the construction of electrospun NY-based nanotextiles and their recent applications in biomedical fields, mainly including surgical sutures, various scaffolds and implants for tissue engineering, smart wearable bioelectronics, and their current and potential applications in the COVID-19 pandemic. At the end, this review highlights and identifies the future needs and opportunities of electrospun NYs and NY-based nanotextiles for clinical use.