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1.
Tissue Engineering - Part A ; 28:228-229, 2022.
Article in English | EMBASE | ID: covidwho-2062829

ABSTRACT

Purpose/Objectives: Bioprinted models of lung tissue are in high demand but in short supply, particularly for addressing the research needs in response to COVID-19 pandemic. The lung is arguably one of the most complex organs in the body, with a multiscale cytoarchitectural organization serving its multiple functions. In particular, the cellular structure of the alveolar sacs poses a big challenge to extrusion bioprinting, which is more adept at capturing the external shape of biological objects than their cell-level details.Methodology: Recently, we proposed a constructive compromise, attainable by bioprinting of equivalent 3D constructs derived from individual (such as 'precision cut lung slices') or stackable (serial histological sections) anatomic images. The advantage of this approach is that in these images, which can be obtained either from regular histology, or confocal fluorescence or electron microscopy (EM), is already incorporated a wealth of structural information. This can be first transferred to '2.5 dimensional' models (by giving them a finite thickness), and then these can be printed layer-by-layer and stacked as tissue-equivalent 3D volumes. Here we illustrate this proposed workflow with 3D printed human lung sections, and with a lung fragment reconstituted from serial sections, while also simulating the infection with SARS-CoV-2 virus in the same constructs by an agent-based modeling approach.Results: As proof of concept, we processed a human lung histological section in CAD, converted it as .stl file and then 3D printed it using as materials both polycaprolactone (by fused filament fabrication), and by the FRESH method using alginate as hydrogel bioink. Similarly, we extracted from a serial EM stack an image selection which was imported in CAD as well and printed as a self-standing object by photolithography. Here we also report the re-purposing of a simulation program of SARS-CoV-2 infection created on the CompuCell 3D (CC3D) platform, to analyze the propagation of infection in cellular patterns derived from the same histological and ultrastructural sections of human lungs. Using it, we explored the spatial distribution and kinetics of several cell classes (infected, virus shedding, apoptotic), the associated viral and cytokine fields, as well as the impact of the presence of generic inflammatory cells, in comparison with the comparable situations when the cell distribution was a uniform epithelial monolayer. We noted a good reproducibility of these simulations, in spite of the section-characteristic cell distribution patterns, and of the initial locations ('seeding') of the viral infection. In addition, we reconstructed thicker virtual tissue slices from multiple single-cell layers for the study of their viral infection as well.Conclusion/Significance: In conclusion, while more sophisticated methods to capture the tissue structure in 3D constructs certainly exist, the extrusion bioprinting is shown here to be capable to offer a simpler, more practical, and more affordable alternative. We also demonstrated how computational simulations on the same images as used in bioprinting, can be used as a useful heuristic instrument to anticipate the results of the interaction of viruses with bioprinted structures that are more complex than cellular monolayers.

2.
European Journal of Molecular and Clinical Medicine ; 9(4):2279-2285, 2022.
Article in English | EMBASE | ID: covidwho-2057977

ABSTRACT

Background: The COVID- 19 infections are associated with wide range of bacterial and fungal co-infections. They may be associated with various comorbidities. Definite diagnosis requires demonstration of fungi in tissue sections or in culture. Yield of organism in culture is suboptimal. Hence histopathology plays critical role in establishing the diagnosis and provide evidence of tissue invasion. Objective(s): To study the histopathological features of fungal infections in sino nasal, oral and orbital area associated with COVID-19 patients. Material(s) and Method(s): One hundred twenty cases of fungal infections involving sinonasal, oral and orbital area in laboratory confirmed COVID-19 positive patients between June-September 2021 were taken for study. Clinical data was recorded, histopathological examination was done along with periodic acid Schiff stain and culture report was obtained. Result(s): The study included 92(76.6%) males and 28(23.3%) females with age ranging from 13 to 78 years. The tissues included debridement, biopsy and excision specimen. Acute inflammation was seen in 8(6.66%) cases, chronic inflammation in 112(93.33%), granulomas in 25, thrombosis in 14, necrosis in 104, angioinvasion in 13, perineuritis in 10 and bone invasion in 18 cases. Mixed fungal infection was seen in 11cases. Conclusion(s): Histopathology remains the mainstay in diagnosis of invasive fungal infections especially when culture is negative. Copyright © 2022 Ubiquity Press. All rights reserved.

3.
Drug Development and Delivery ; 22(4):18-23, 2022.
Article in English | Scopus | ID: covidwho-2012508
4.
Journal of Clinical Oncology ; 40(16), 2022.
Article in English | EMBASE | ID: covidwho-2009544

ABSTRACT

Background: Approximately 70%-85% of patients who undergo sentinel lymph node biopsy (SLNb) show no nodal metastasis in the sentinel node (SN). The clinicopathological and gene expression profile (CP-GEP) model (Merlin Assay) was developed and validated to identify patients that may forgo the SLNb surgery due to their low risk for for nodal metastasis This study was initiated during the first wave of Covid-19 pandemic to allow for surgical triage on SLNb and evaluate the implementation of the Merlin assay in clinical practice. Methods: This study was conducted in four designated melanoma centers in the Netherlands. Patients (age > 18y) with newly diagnosed melanoma of the skin, eligible to undergo SLNb were screened for study inclusion. Main exclusion criteria was prior history of primary melanoma (> T1b) in the past 5 years. After enrollment, tissue sections of the primary melanoma were centrally reviewed at the Erasmus MC Cancer Institute to determine Breslow thickness at primary diagnosis. FFPE tumor tissue was dispatched for molecular analysis of eight target genes known to play a role in cancer development. In combination with age, Breslow thickness, and GEP outcome, risk of having nodal metastasis was calculated. Results were binary presented as 'CP-GEP low risk' and 'CPGEP high risk'. SLNb status was used as gold standard for comparison. Results: A total of 177 patients were analyzed using the CP-GEP model. Median age was 64 years (IQR 52-73) Median Breslow thickness was 1.4mm (IQR 1.0-2.4). Of all patients 28.2% was diagnosed with T1, 40.7% with T2 and 20.9% with T3 melanoma. Corresponding positivity rate was 7%, 14% and 29% respectively. A total of 24 out of 177 patients had a positive SLNb. Median turn-around time from inclusion to CP-GEP result was 15 days. Overall 37.1.% of patients had a CP-GEP low risk profile. The CP-GEP model had a NPV of 94.6%. Conclusions: This is the first prospective multicenter implementation study for the Merlin assay. Results are in line with previous validation studies. The CP-GEP model could accurately identify patients at low risk for SN metastasis. Implementation in clinical practice is feasible based on current turn-around time. In the future, using the Merlin assay to deselect patients for SLNB may allow for a reduction of surgery in patients with melanoma.

5.
Annals of the Rheumatic Diseases ; 81:1432, 2022.
Article in English | EMBASE | ID: covidwho-2008833

ABSTRACT

Background: The etiology of pancreatitis is heterogeneous;it may be due to chronic excessive alcohol use, gallstones, medications, infections, autoimmune diseases, metabolic disorders, trauma, congenital malformations etc. Objectives: The aim of this study has been to describe a hypothetic pathway of chronic pancreatitis in post-Covid 19 condition, based on the role of autoimmune and bacterial septic vasculitis in the pathogenesis of chronic pancreatitis (ChrP) in rheumatoid arthritis (RA). Methods: At the National Institute of Rheumatology 9475 patients died between 1969 and 1992;among them 161 with RA and all of them were autopsied. RA was confrmed clinically according to the criteria of the ACR. Tissue samples of pancreas were available for histologic evaluation in 111 patients. Pancreatitis and vasculitis were determined and characterized histo-logically [1,2]. The possible role of autoimmune vasculitis and bacterial septic vasculitis in the pathogenesis of ChrP was analyzed by Pearson's chi-squared (χ2) test. Results: ChrP-characterized by diffuse and/or focal fbrosis and atrophy-was present in 10 (9.01%) of 111 patients. Systemic vasculitis complicated RA in 28 (25.23%) of 111 patients. Twenty-five (89.3 %) of 28 systemic vasculitis proved to be of autoimmune origin. Autoimmune vasculitis involved the pancreatic blood vessels (pAV) in 8 (32.0 %) of these 25 patients. Non-specifc (n=37), fbrinoid necrotic (n=14), and granulomatous type (n=5) of pAV were detected side by side in the same histologic section, involving pancreatic arteries of different sizes. The veins and venules were not involved. p AV was not associated with chronic pancreatitis. The relationship between p AV and ChrP was inverse with a negative colliquation coefficient (c=-1.0, χ2=0. 0801, p <0.7772-NS). Three (10.7 %) of 28 systemic vasculitis cases proved to be of septic (bacterial) origin. Pancreatic blood vessels (pSV) were involved in 2 (66.7 %) of these 3 patients. Granulomatous vasculitis was not seen with pSV, and the veins and venules were also spared. Non-specifc (n=9), fbrinoid necrotic (n=2) vasculitis involving different size of pancreatic arteries were associated with chronic pancreatitis. The relationship between pAV and ChrP was signifcant (c=0.92308, χ2=6.3201, p <0.012). Conclusion: Chronic pancreatitis is characterized clinically by abdominal pain and diarrhea, which are common in post-Covid 19 condition [2]. The strong and signifcant correlation between pSV and ChrP indicates that subclinical or manifest bacterial septic processes may play a role in the pathogenesis of ChrP. Hypothetically a similar pathway is plausible in post-Covid 19 chronic pancreatitis due to viral infection and vasculitis, analogous to bacterial septic vasculitis. Systemic vasculitis of autoimmune origin involving blood vessels of the pancreas may cause a special multifocal relapsing lipo-necrotic pancreatitis [1,2], and according to our results, do not influence the prevalence of ChrP. The autoimmune origin of pancreatic vasculitis may be excluded histologically by the presence of granulomatous vasculitis of the most frequently involved arterioles and small arteries.

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