Therapeutic Endoscopy during COVID-19 Pandemic: An Observational Study from Bangladesh.

How to cite this article: Al Mahtab M, Huq AKMF, Rahman MF, et al. Therapeutic Endoscopy during COVID-19 Pandemic: An Observational Study from Bangladesh. Euroasian J Hepato-Gastroenterol 2020;10(1): 47-49.

Real-life Management Strategy of COVID-19 Patients in Bangladesh with No Death: An Observational and Cohort Study.

BACKGROUND: Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been declared as pandemic by World Health Organization (WHO) with increasing morbidity (more than 4.6 million patients) and mortality (300,000 deaths). The world-wide target of management COVID-19 is to reduce complications with available management options; this become highly variable from country to country and even within different regions of the same country. AIM AND OBJECTIVE: This observational prospective study represents a single center study in which all patients in this cohort received almost similar medicines and care. MATERIALS AND METHODS: All patients in this cohort (N: 32) were positive for SARS-CoV-2 by polymerase chain reaction (PCR) with variable presenting symptoms. The management strategy included Standard of Care (SoC) and administration of hydroxychloroquine and doxycycline. Out of 32 patients, 9 patients also received favipiravir. All patients were followed until they were discharged after negativity of SARS-CoV-2 confirmed by PCR on two consecutive occasions taken within 2 days. RESULTS: No death has been recorded in this cohort of 32 patients within the study period. The average hospital staying duration was 13.9 days with a range of 8-21 days. All patients were discharged with improvement of subjective symptoms and SARS-CoV-2 negativity. The vital signs (pulse, blood pressure) as well as and levels of electrolyte and blood counts were within normal and acceptable ranges at the time of discharge. CONCLUSION: The study presented here provide and evidence of a real-life situation of management of limited numbers of COVID-19 patients at a tertiary center of Bangladesh. This study inspires optimism that proper diagnosis, establishment of effective inclusion and exclusion criteria, ensuring application of proper SoC with drugs available in Bangladesh may be a practical option for management of COVID-19 in the country. HOW TO CITE THIS ARTICLE: Huq AKMF, Rahman MF, Islam MA, et al. Real-life Management Strategy of COVID-19 Patients in Bangladesh with No Death: An Observational and Cohort Study. Euroasian J Hepato-Gastroenterol 2020;10(1):31-35.

Skin substitute-assisted repair shows reduced dermal fibrosis in acute human wounds validated simultaneously by histology and optical coherence tomography.

Skin substitutes are heterogeneous biomaterials designed to accelerate wound healing through provision of replacement extracellular matrix. Despite growing evidence for their use in chronic wounds, the role of skin substitutes in acute wound management and their influence on fibrogenesis remains unclear. Skin substitute characteristics including biocompatibility, porosity, and elasticity strongly influence cellular behavior during wound healing. Thus, we hypothesize that structural and biomechanical variation between biomaterials may induce differential scar formation after cutaneous injury. The following human prospective cohort study was designed to investigate this premise. Four 5-mm full thickness punch biopsies were harvested from 50 volunteers. In all cases, site 1 healed by secondary intention, site 2 was treated with collagen-GAG scaffold (CG), and decellularised dermis (DCD) was applied to site 3 while tissue extracted from site 4 was replaced (autograft). Healing tissue was assessed weekly with optical coherence tomography (OCT), before being excised on days 7, 14, 21, or 28 depending on study group allocation for later histological and immunohistochemical evaluation. Extracted RNA was used in microarray analysis and polymerase chain reaction of highlighted genes. Autograft treatment resulted in minimal fibrosis confirmed immunohistochemically and with OCT through significantly lower collagen I levels (p = 0.047 and 0.03) and reduced mean grayscale values (p = 0.038 and 0.015), respectively. DCD developed intermediate scar formation with partial rete ridge reformation and reduced fasiculonodular fibrosis. It was uniquely associated with late up-regulation of matrix metalloproteinases 1 and 3, oncostatin M, and interleukin-10 (p = 0.007, 0.04, 0.019, 0.019). Regenerated dermis was significantly thicker in DCD and autografts 28 days post-injury compared with control and CG samples (p = 0.003 and < 0.0001). In conclusion, variable fibrotic outcomes were observed in skin substitute-treated wounds with reduced scarring in autograft and DCD samples compared with controls. OCT enabled concurrent assessment of wound morphology and quantification of dermal fibrosis.

Electrical stimulation enhances epidermal proliferation in human cutaneous wounds by modulating p53-SIVA1 interaction.

Cutaneous wounds establish endogenous "wound current" upon injury until re-epithelialization is complete. Keratinocyte proliferation, regulated partly by p53, is required for epidermal closure. SIVA1 promotes human double minute 2 homolog (HDM2)-mediated p53 regulation. However, the role of SIVA1 in wound healing is obscure. Here, we report that electrical stimulation (ES) accelerates wound healing by upregulating SIVA1 and its subsequent ability to modulate p53 activities. Cultured donut-shaped human skin explants, subjected to ES, exhibited better epidermal stratification, increased proliferation, and upregulation of gene and protein expression of HDM2/SIVA1, compared with non-ES-treated explants. ES significantly increased in vitro keratinocyte proliferation and phospho-p53-SIVA1 interaction; however, this showed stable expression of phospho-p53, which increased significantly in the absence of SIVA1. Here, HDM2 alone was unable to downregulate nuclear-accumulated phospho-p53, which was evident from decreased proliferation and increased sub-G1 population seen by flow cytometry. Further examination of the epidermis of human cutaneous wounds showed higher p53-SIVA1 coexpression and proliferation 7 days after injury in ES-treated wounds compared with control wounds. In summary, ES-inducible SIVA1 modulates p53 activities in proliferating keratinocytes, and exogenous ES affects p53/HDM2/SIVA1 axis leading to increased proliferation during re-epithelialization. This highlights ES as a potential strategy for enhancing cutaneous repair.

Altered expression of hyaluronan synthase and hyaluronidase mRNA may affect hyaluronic acid distribution in keloid disease compared with normal skin.

Keloid disease (KD) is a fibroproliferative disorder characterised partly by an altered extracellular matrix (ECM) profile. In fetal scarring, hyaluronic acid (HA) expression is increased, but is reduced in KD tissue compared with normal skin (NS). The expression of Hyaluronan Synthase (HAS) and hyaluronidase (HYAL) in KD and NS tissue were investigated for the first time using a range of techniques. Hyaluronan synthase and HYAL mRNA expression were significantly increased in NS tissue compared with KD tissue (P < 0.05). Immunohistological analysis of tissue indicated an accumulation of HAS and HYAL protein expression in KD compared with NS due to the thicker epidermis. No differences were observed in mRNA or protein expression in KD and NS fibroblasts. Reduced expression of HAS and HYAL may alter HA synthesis, degradation and accumulation in KD. Better understanding of the role of HA in KD may lead to novel therapeutic approaches to address the resulting ECM imbalance.

The role of skin substitutes in the management of chronic cutaneous wounds.

Chronic wounds, including diabetic and venous ulcers, represent disruption of normal healing processes resulting in a pathological state of nonhealing cutaneous inflammation. They place an increasingly significant economic burden on healthcare providers as their prevalence is rising in keeping with an aging population. Current treatment modalities are slow acting and resource intensive. Bioengineered skin substitutes from autogenic, allogenic, or xenogenic sources have emerged as a new and alternative therapeutic option. A range of such products is licensed for clinical use, which differ in terms of structure and cellular content. Placed directly onto a prepared wound bed, skin substitutes may stimulate or accelerate healing by promoting revascularization, cellular migration, and repopulation of wound fields through provision of an appropriate scaffold material to facilitate these processes. Products containing fetal or autologous cells also benefit from early release of bioactive molecules including growth factors and cytokines. To date, limited numbers of randomized controlled trials studying skin substitutes have been published but evidence from case series and case-control studies is encouraging. This review discusses chronic wound biology, the influence that skin substitutes can exert on this environment, the products currently available, and examines the evidence for their use in chronic wound management.

Mining metabolites: extracting the yeast metabolome from the literature.

Text mining methods have added considerably to our capacity to extract biological knowledge from the literature. Recently the field of systems biology has begun to model and simulate metabolic networks, requiring knowledge of the set of molecules involved. While genomics and proteomics technologies are able to supply the macromolecular parts list, the metabolites are less easily assembled. Most metabolites are known and reported through the scientific literature, rather than through large-scale experimental surveys. Thus it is important to recover them from the literature. Here we present a novel tool to automatically identify metabolite names in the literature, and associate structures where possible, to define the reported yeast metabolome. With ten-fold cross validation on a manually annotated corpus, our recognition tool generates an f-score of 78.49 (precision of 83.02) and demonstrates greater suitability in identifying metabolite names than other existing recognition tools for general chemical molecules. The metabolite recognition tool has been applied to the literature covering an important model organism, the yeast Saccharomyces cerevisiae, to define its reported metabolome. By coupling to ChemSpider, a major chemical database, we have identified structures for much of the reported metabolome and, where structure identification fails, been able to suggest extensions to ChemSpider. Our manually annotated gold-standard data on 296 abstracts are available as supplementary materials. Metabolite names and, where appropriate, structures are also available as supplementary materials. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s11306-010-0251-6) contains supplementary material, which is available to authorized users.

Supersensitive mutation: two case reports of non-small-cell lung cancer treated with epidermal growth factor receptor tyrosine kinase inhibitors.

Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are indicated in second-line treatment for non-small-cell lung cancer and are, in general, well tolerated. In some patients, side effects can be problematic, necessitating dose attenuation and changes in frequency of administration. A lung tumor with an EGFR mutation confers a high treatment response rate to EGFR TKIs. We present the case reports of 2 patients, both with EGFR mutations in which excellent responses were seen despite dosages and administration frequencies far below recommended levels. In addition, in the face of apparent resistance, small increases in doses overcame this. The possible factors involved in response and resistance to EGFR TKIs and issues around length of treatment are discussed.

Construction of an annotated corpus to support biomedical information extraction.

BACKGROUND: Information Extraction (IE) is a component of text mining that facilitates knowledge discovery by automatically locating instances of interesting biomedical events from huge document collections. As events are usually centred on verbs and nominalised verbs, understanding the syntactic and semantic behaviour of these words is highly important. Corpora annotated with information concerning this behaviour can constitute a valuable resource in the training of IE components and resources. RESULTS: We have defined a new scheme for annotating sentence-bound gene regulation events, centred on both verbs and nominalised verbs. For each event instance, all participants (arguments) in the same sentence are identified and assigned a semantic role from a rich set of 13 roles tailored to biomedical research articles, together with a biological concept type linked to the Gene Regulation Ontology. To our knowledge, our scheme is unique within the biomedical field in terms of the range of event arguments identified. Using the scheme, we have created the Gene Regulation Event Corpus (GREC), consisting of 240 MEDLINE abstracts, in which events relating to gene regulation and expression have been annotated by biologists. A novel method of evaluating various different facets of the annotation task showed that average inter-annotator agreement rates fall within the range of 66% - 90%. CONCLUSION: The GREC is a unique resource within the biomedical field, in that it annotates not only core relationships between entities, but also a range of other important details about these relationships, e.g., location, temporal, manner and environmental conditions. As such, it is specifically designed to support bio-specific tool and resource development. It has already been used to acquire semantic frames for inclusion within the BioLexicon (a lexical, terminological resource to aid biomedical text mining). Initial experiments have also shown that the corpus may viably be used to train IE components, such as semantic role labellers. The corpus and annotation guidelines are freely available for academic purposes.