Poor prognosis indicators of type-2 diabetic COVID-19 patients.

Diabetes is associated with a worse prognosis and a high risk of morbidity and mortality in COVID-19 patients. We aimed to evaluate the main factors involved in the poor prognosis in diabetic patients. A total of 984 patients diagnosed with COVID-19 admitted to the hospital were included in this study. Patients were first divided into type-2 diabetic (DM+) and non-diabetic (DM-) groups. The participants were analyzed based on the National Early Warning Score (NEWS) and on the Quick-Sequential Organ Failure Assessment (qSOFA) to find the best prognostic risk score for our study. The DM+ and DM- groups were divided into non-severe and severe groups. Comparative and correlative analyses were used to identify the physiological parameters that could be employed for creating a potential risk indicator for DM+ COVID-19 patients. We found a poorer prognosis for the DM+ COVID-19 patients with a higher ICU admission rate, mechanical ventilation rate, vasopressor use, dialysis, and longer treatment times compared with the DM- group. DM+ COVID-19 patients had increased plasma glucose, lactate, age, urea, NEWS, and D-dimer levels, herein referred to as the GLAUND set, and worse prognosis and outcomes when compared with infected DM- patients. The NEWS score was a better indicator for assessing COVID-19 severity in diabetic patients than the q-SOFA score. In conclusion, diabetic COVID-19 patients should be assessed with the NEWS score and GLAUND set for determining their prognosis COVID-19 prognosis.

Poor prognosis indicators of type-2 diabetic COVID-19 patients

Diabetes is associated with a worse prognosis and a high risk of morbidity and mortality in COVID-19 patients. We aimed to evaluate the main factors involved in the poor prognosis in diabetic patients. A total of 984 patients diagnosed with COVID-19 admitted to the hospital were included in this study. Patients were first divided into type-2 diabetic (DM+) and non-diabetic (DM-) groups. The participants were analyzed based on the National Early Warning Score (NEWS) and on the Quick-Sequential Organ Failure Assessment (qSOFA) to find the best prognostic risk score for our study. The DM+ and DM- groups were divided into non-severe and severe groups. Comparative and correlative analyses were used to identify the physiological parameters that could be employed for creating a potential risk indicator for DM+ COVID-19 patients. We found a poorer prognosis for the DM+ COVID-19 patients with a higher ICU admission rate, mechanical ventilation rate, vasopressor use, dialysis, and longer treatment times compared with the DM- group. DM+ COVID-19 patients had increased plasma glucose, lactate, age, urea, NEWS, and D-dimer levels, herein referred to as the GLAUND set, and worse prognosis and outcomes when compared with infected DM- patients. The NEWS score was a better indicator for assessing COVID-19 severity in diabetic patients than the q-SOFA score. In conclusion, diabetic COVID-19 patients should be assessed with the NEWS score and GLAUND set for determining their prognosis COVID-19 prognosis.

Differential effects of palmitoleic acid on human lymphocyte proliferation and function.

BACKGROUND: Palmitoleic acid (PA) is a n-7 monounsaturated fatty acid (MUFA) secreted by adipose tissue and related to decreased insulin resistance in peripheral tissues. Evidences have been shown that PA also decreased proinflammatory cytokine expression in cultured macrophages. Although studies have shown that other fatty acids (FAs) modulate several lymphocyte functions, the specific effect of PA on these cells is unknown. The aim of the present study was to evaluate the possible influence of PA on activation and differentiation of human lymphocytes in comparison to oleic acid (OA). METHODS: Human lymphocytes were isolated from peripheral blood of health men and cultured in the presence of growing concentrations of PA or OA (5 to 200 µM), for 24 h. After that, cells were collected and cytotoxicity evaluated by flow cytometry. Then, we analyzed proliferative capacity in lymphocytes treated with non toxic concentrations of PA and OA (25 and 50 µM, respectively), in the presence or absence of concanavalin A (ConA). The Th1/Th2/Th17 cytokine production was determined by the Cytometric Bead Array. CD28 and CD95 surface expression and T regulatory cell percentage were determined by flow cytometry. RESULTS: We observed that PA is toxic to lymphocytes above 50 µM. PA promoted a decrease of lymphocyte proliferation stimulated by ConA in both concentrations. PA also decreased CD28 externalization and increased CD95. On the other hand, OA did not alter these parameters. In the same way, PA reduced IL6, IFN-gamma, TNF-alpha and IL17A production in both concentration and IL2 only at 50 µM (in the presence of ConA). OA promoted IFN-gamma reduction in both concentrations and an increase of IL-2, IL4 and IL10 at 25 µM. Both fatty acids decreased the percentage of T regulatory cells. CONCLUSION: In conclusion, PA promoted a suppressive effect on lymphocyte proliferation characterized by a decrease of Th1 and Th17 response, and co-stimulatory molecule (CD28). However, OA increased lymphocyte proliferation through IL2 production and Th2 response. These results also show a more suppressive effect of PA on lymphocytes in comparison to OA.

Serum amyloid A induces reactive oxygen species (ROS) production and proliferation of fibroblast.

Serum amyloid A (SAA) levels are elevated highly in acute phase response and elevated slightly and persistently in chronic diseases such as rheumatoid arthritis and diabetes. Given that fibroblasts exert profound effects on progression of inflammatory chronic diseases, the aim of this study was to investigate the response of fibroblasts to SAA. A dose-dependent increase in O(2) (-) levels was observed by treatment of fibroblasts with SAA (r = 0·99 and P ≤ 0·001). In addition, the expression of p47-phox was up-regulated by SAA (P < 0·001) and diphenyliodonium (DPI), a nicotinamide adenine dinucleotide phosphate (NADPH) oxidase inhibitor, reduced the release of O(2) (-) by 50%. Also, SAA raised fibroblast proliferation (P < 0·001) and this effect was completely abolished by the addition of anti-oxidants (P < 0·001). These findings support the notion that, in chronic inflammatory sites, SAA activated fibroblast proliferation and ROS production.

Moderate exercise improves leucocyte function and decreases inflammation in diabetes.

The genesis and progression of diabetes occur due in part to an uncontrolled inflammation profile with insulin resistance, increased serum levels of free fatty acids (FFA), proinflammatory cytokines and leucocyte dysfunction. In this study, an investigation was made of the effect of a 3-week moderate exercise regimen on a treadmill (60% of VO2(max) , 30 min/day, 6 days a week) on inflammatory markers and leucocyte functions in diabetic rats. The exercise decreased serum levels of tumour necrosis factor (TNF)-α (6%), cytokine-induced neutrophil chemotactic factor 2 alpha/beta (CINC-2α/ß) (9%), interleukin (IL)-1ß (34%), IL-6 (86%), C-reactive protein (CRP) (41%) and FFA (40%) in diabetic rats when compared with sedentary diabetic animals. Exercise also attenuated the increased responsiveness of leucocytes from diabetics when compared to controls, diminishing the reactive oxygen species (ROS) release by neutrophils (21%) and macrophages (28%). Exercise did not change neutrophil migration and the proportion of neutrophils and macrophages in necrosis (loss of plasma membrane integrity) and apoptosis (DNA fragmentation). Serum activities of creatine kinase (CK) and lactate dehydrogenase (LDH) were not modified in the conditions studied. Therefore, physical training did not alter the integrity of muscle cells. We conclude that moderate physical exercise has marked anti-inflammatory effects on diabetic rats. This may be an efficient strategy to protect diabetics against microorganism infection, insulin resistance and vascular complications.

The effect of an adventure race on lymphocyte and neutrophil death.

The effect of an adventure race (Ecomotion Pró), which lasted for 4-5 days, on neutrophil and lymphocyte death from elite athletes was investigated. Blood was collected from 11 athletes at rest and after the adventure race. The following parameters of cell death were measured in neutrophils and lymphocytes: cell membrane integrity, DNA fragmentation, mitochondrial transmembrane depolarization and reactive oxygen species (ROS) production. Phagocytosis capacity was also evaluated in neutrophils. The adventure race raised the proportion of cells with the loss of membrane integrity; lymphocytes by 14% and neutrophils by 16.4%. The proportion of lymphocytes with DNA fragmentation (2.9-fold) and mitochondrial transmembrane depolarization (1.5-fold) increased. However, these parameters did not change in neutrophils. ROS production remained unchanged in lymphocytes, whereas an increase by 2.2-fold was found in neutrophils due to the race. Despite these changes, the phagocytosis capacity did not change in neutrophils after the race. In conclusion, the Ecomotion Pró race-induced neutrophil death by necrosis (as indicated by the loss of membrane integrity) and led to lymphocyte death by apoptosis (as indicated by increase DNA fragmentation and depolarization of mitochondrial membrane).

Neutrophils and monocytes as potentially important sources of proinflammatory cytokines in diabetes.

Neutrophils and monocytes play a central role in host defence. The invading leucocytes are capable of synthesizing and releasing a variety of proinflammatory mediators including cytokines. Given the importance of cytokines in the progression of chronic and acute inflammatory processes, we aimed to ascertain whether the release of interleukin (IL)-8, IL-1beta, tumour necrosis factor (TNF)-alpha and IL-1ra of neutrophils and monocytes was modified in diabetes. To this end, we measured the release of cytokines in suspensions of cell culture in basal and lipopolysaccharide (LPS)-stimulated conditions. In basal conditions, neutrophils of diabetics release 1.6, 3.2, 1.9 and 1.9-fold higher amounts of IL-8, IL-1beta, TNF-alpha and IL-1ra, respectively, than do healthy controls. Under our experimental conditions, this effect was more evident for neutrophils than for monocytes. Incremental cytokine production was also found to occur when neutrophils were stimulated with LPS. IL-8, IL-1beta and TNF-alpha increased, respectively, by 4.0, 1.7 and 2.8-fold. Although the effect was more marked for neutrophils, monocytes showed a tendency for increased cytokine production. The discovery of this increase in cytokines released by the neutrophils of diabetics contributes towards a clearer understanding of other deficiencies described for neutrophils in diabetes, such as the migration of neutrophils to inflammatory sites, phagocytes, release of lytic proteases, production of reactive oxygen species and apoptosis. The excessive production of cytokines may lead to inappropriate activation and tissue injury and even to increased susceptibility to invasive microorganisms. Thus, the increased responsiveness of neutrophils of diabetics demonstrated in this study may be considered part of the scenario of diabetes physiopathology.

Cytological and histopathological studies of otitis media with effusion.

Middle ear fluid contains such cells as neutrophils, macrophages, and lymphocytes. There have been numerous reports dealing with these cellular components in the fluid. This study was undertaken to investigate interrelation between the type of predominant cells in the fluid and the stage of disease in adults and children. The study also included bacterial isolation from fluid for comparison of detection rates between adults and children, and microscopic examination of temporal bone from 2 adult patients with otitis media with effusion complicating tumors of head and neck. Thirty-two ears of adult patients and 40 ears of children both having received myringotomy were studied. The fluid specimens were obtained from middle ears examined microscopically with May-Giemsa stain and with alpha-Naphthyl butyrate esterase and Naphtohol AS-D chloroacetate double stains for identification of macrophages. Histopathological studies of the temporal bone were examined with hematoxylineosin stain. In adults, neutrophils were predominant in the fluid of 54.5% of subacute cases while the predominant cell type was macrophages in 45% of chronic cases. Neutrophils were the predominant type in 62.2% of children with chronic stage. Bacteria were demonstrated in 26.0% of the adult cases and in 21.6% of the children. By histopathological examination of the temporal bones, neutrophils were found in the fluid of case 1, and a large number of macrophages in the fluid and fibrosis of the tympanic cavity were found in case 2.