Clinical characteristics and outcomes in diabetes patients admitted with COVID-19 in Dubai: a cross-sectional single centre study.

AimTo describe the clinical characteristics and outcomes of hospitalised Coronavirus Disease 2019 (COVID-19) patients with diabetes. MethodsA cross-sectional observational study was conducted in patients with diabetes admitted with COVID-19 to Mediclinic Parkview Hospital in Dubai, United Arab Emirates (UAE) from 30th March to 7th June 2020. They had laboratory and/or radiologically confirmed severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), known as COVID-19. Variation in characteristics, length of stay in hospital, diabetes status, comorbidities and outcomes were examined. ResultsA total of 103 patients with confirmed COVID-19 presentations had diabetes. During the same timeframe, 410 patients overall were admitted with COVID-19 infection. This gives a total proportion of persons admitted with COVID-19 infection and coexistent diabetes/prediabetes of 25%. 67% (n=69) of the COVID-19 diabetes cohort were male. Patients admitted with COVID-19 and diabetes represented 17 different ethnicities. Of these, 59.2% (n=61) were Asians and 35% (n=36) were from Arab countries. Mean age (SD) was 54 ({+/-}12.5) years. 85.4% (n=88) were known to have diabetes prior to admission, while 14.6% (n=15) were newly diagnosed with either diabetes or prediabetes during admission. Most patients in the study cohort had type 2 diabetes or prediabetes, with only 3% overall having type 1 diabetes (n=3). 46.9% of patients had evidence of good glycaemic control of their diabetes during the preceding 4-12 weeks prior to admission as defined arbitrarily by admission HbA1c <7.5%. 73.8% (n=76) had other comorbidities including hypertension, ischaemic heart disease, and dyslipidaemia. Laboratory data (Mean {+/-} SD) on admission for those who needed ward-based care versus those needing intensive care unit (ICU) care: Fibrinogen 462.75 ({+/-}125.16) mg/dl vs 660 ({+/-}187.58) mg/dl ; D-dimer 0.66 ({+/-}0.55) {micro}g/ml vs 2.3 ({+/-}3.48) {micro}g/ml; Ferritin 358.08 ({+/-}442.05) mg/dl vs 1762.38 ({+/-}2586.38) mg/dl; and CRP 33.9 ({+/-}38.62) mg/L vs 137 ({+/-}111.72) mg/L were all statistically significantly higher for the ICU cohort (p<0.05). Average length of stay in hospital was 14.55 days. 28.2% of patients needed ICU admission. 4.9% (n=5) overall died during hospitalisation (all in ICU). ConclusionsIn this single-centre study in Dubai, 25% of patients admitted with COVID-19 also had diabetes/prediabetes. Most diabetes patients admitted to hospital with COVID-19 disease were males of Asian origin. 14.6% had new diagnosis of diabetes/prediabetes on admission. The majority of patients with diabetes/prediabetes and COVID-19 infection had other important comorbidities (n=76; 73.8%). Only 4 patients had negative COVID-19 RT-PCR but had pathognomonic changes of COVID-19 radiologically. Our comprehensive laboratory analysis revealed distinct abnormal patterns of biomarkers that are associated with poor prognosis: Fibrinogen, D-dimer, Ferritin and CRP levels were all statistically significantly higher (p<0.05) at presentation in patients who subsequently needed ICU care compared with those patients who remained ward-based. 28.2% overall needed ICU admission, out of which 5 patients died. More studies with larger sample sizes are needed to compare data of COVID-19 patients admitted with and without diabetes within the UAE region.

The transcriptional profile of circulating myeloid derived suppressor cells correlates with tumor development and progression in mouse.

Myeloid derived suppressor cells (MDSCs) play key roles in cancer development. Accumulation of peripheral-blood MDSCs (PB-MDSCs) corresponds to the progression of various cancers, but provides only a crude indicator. We aimed toward identifying changes in the transcriptional profile of PB-MDSCs in response to tumor growth. CT26 colon cancer cells and B16 melanoma cells (106) were inoculated into peritoneal cavities of BALB/c mice and subcutaneously to C57-black mice, respectively. The circulating levels and global transcriptional patterns of PB CD11b+Ly6g+ MDSCs were assessed in control mice, and 4, 8, and 11 days following tumor cell inoculation. Although a significant accumulation of PB-MDSCs was demonstrated only 11 days following tumor induction, a pronounced transcriptional response was identified already on day 4 while the tumor was ~1 mm in size. Further transcriptional changes correlated with different stages of tumor growth. Key MDSC genes and canonical signaling pathways were activated along tumor progression. This phenomenon was demonstrated in both cancer models, and a consensus set of 817 genes, involved in myeloid cell recruitment and angiogenesis, was identified. The data suggest that the transcriptional signatures of PB-MDSC may serve as markers for tumor progression, as well as providing potential targets for future therapies.

CD11b+Ly6G+ myeloid-derived suppressor cells promote liver regeneration in a murine model of major hepatectomy.

Liver regeneration depends on sequential activation of pathways and cells involving the remaining organ in recovery of mass. Proliferation of parenchyma is dependent on angiogenesis. Understanding liver regeneration-associated neovascularization may be useful for development of clinical interventions. Myeloid-derived suppressor cells (MDSCs) promote tumor angiogenesis and play a role in developmental processes that necessitate rapid vascularization. We therefore hypothesized that the MDSCs could play a role in liver regeneration. Following partial hepatectomy, MDSCs were enriched within regenerating livers, and their depletion led to increased liver injury and postoperative mortality, reduced liver weights, decreased hepatic vascularization, reduced hepatocyte hypertrophy and proliferation, and aberrant liver function. Gene expression profiling of regenerating liver-derived MDSCs demonstrated a large-scale transcriptional response involving key pathways related to angiogenesis. Functionally, enhanced reactive oxygen species production and angiogenic capacities of regenerating liver-derived MDSCs were confirmed. A comparative analysis revealed that the transcriptional response of MDSCs during liver regeneration resembled that of peripheral blood MDSCs during progression of abdominal tumors, suggesting a common MDSC gene expression profile promoting angiogenesis. In summary, our study shows that MDSCs contribute to early stages of liver regeneration possibly by exerting proangiogenic functions using a unique transcriptional program.-Nachmany, I., Bogoch, Y., Sivan, A., Amar, O., Bondar, E., Zohar, N., Yakubovsky, O., Fainaru, O., Klausner, J. M., Pencovich, N. CD11b+Ly6G+ myeloid-derived suppressor cells promote liver regeneration in a murine model of major hepatectomy.

Gas2l3 is essential for brain morphogenesis and development.

Growth arrest-specific 2-like 3 (Gas2l3) is a newly discovered cell cycle protein and a cytoskeleton orchestrator that binds both actin filament and microtubule networks. Studies of cultured mammalian cells established Gas2l3 as a regulator of the cell division process, in particular cytokinesis and cell abscission. Thus far, the role of Gas2l3 in vivo remains entirely unknown. In order to investigate Gas2l3 in developing vertebrates, we cloned the zebrafish gene. Spatiotemporal analysis of gas2l3 expression revealed a ubiquitous maternal transcript as well as a zygotic transcript primarily restricted to brain tissues. We next conducted a series of loss-of-function experiments, and searched for developmental anomalies at the end of the segmentation period. Our analysis revealed abnormal brain morphogenesis and ventricle formation in gas2l3 knockdown embryos. This signature phenotype could be rescued by elevated levels of gas2l3 RNA. At the tissue level, gas2l3 downregulation interferes with cell proliferation, suggesting that the cell cycle activities of Gas2l3 are essential for brain tissue homeostasis. Altogether, this study provides the first insight into the function of gas2l3 in vivo, demonstrating its essential role in brain development.