Spontaneous NETosis in diabetes: A role of hyperglycemia mediated ROS and autophagy.

Type 2-diabetes, particularly poorly controlled diabetes, is a risk factor for several infections such as lower respiratory tract and skin infections. Hyperglycemia, a characteristic downstream effect of poorly controlled diabetes, has been shown to impair the function of immune cells, in particular neutrophils. Several studies have demonstrated that hyperglycemia-mediated priming of NADPH oxidase results in subsequent elevated levels of reactive oxygen species (ROS). In healthy neutrophils, ROS plays an important role in pathogen killing by phagocytosis and by induction of Neutrophil Extracellular Traps (NETs). Given the key role of ROS in autophagy, phagocytosis and NETosis, the relationship between these pathways and the role of diabetes in the modulation of these pathways has not been explored previously. Therefore, our study aimed to understand the relationship between autophagy, phagocytosis and NETosis in diabetes. We hypothesized that hyperglycemia-associated oxidative stress alters the balance between phagocytosis and NETosis by modulating autophagy. Using whole blood samples from individuals with and without type 2-diabetes (in the presence and absence of hyperglycemia), we demonstrated that (i) hyperglycemia results in elevated levels of ROS in neutrophils from those with diabetes, (ii) elevated levels of ROS increase LCIII (a marker for autophagy) and downstream NETosis. (iii) Diabetes was also found to be associated with low levels of phagocytosis and phagocytic killing of S. pneumoniae. (iv) Blocking either NADPH oxidase or cellular pathways upstream of autophagy led to a significant reduction in NETosis. This study is the first to demonstrate the role of ROS in altering NETosis and phagocytosis by modulating autophagy in type 2-diabetes. GRAPHICAL ABSTRACT.

"Tocilizumab-an option for patients with COVID-19 associated cytokine release syndrome: A single center experience", a retrospective study-original article.

BACKGROUND: The first case of Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was diagnosed in Wuhan, China in 2019. In the first half of 2020, this disease has already converted into a global pandemic. This study aimed to find that treatment of patients with COVID-19 pneumonia with Tocilizumab or steroids was associated with better outcomes. Objectives: To analyze the effectiveness of Tocilizumab in moderate to severe Covid-19 patients based on predefined assessment criteria . Study Settings: Single-center, Fatima Memorial Hospital, Lahore. STUDY DESIGN: Quasi-experimental. DURATION OF STUDY: From May 12, 2020 to June 12, 2020. PATIENTS & METHODS SAMPLE SIZE AND TECHNIQUE: Sample size was 93; 33 patients were kept in the experimental group, given Tocilizumab, 8 mg/kg intravenously or 162 mg subcutaneously, and the rest of the 60 patients were given corticosteroids, methylprednisolone 80 mg/day. Consecutive sampling. Failure of therapy was labeled when patients were intubated or died, and the endpoints were failure-free survival which was the primary endpoint, and overall survival secondary at the time of discharge. RESULTS: A total of 93 patients were enrolled, the Tocilizumab (TCZ) group (case) and Corticosteroid (CS) group (Control). The median age was 58 years (IQR-21), 37 (39.8%) patients with diabetes mellitus, 11 (11.8%) in the TCZ group, and 26 (28%) in the CS group. On the whole, the total median hospital stay in days was 7 with IQR (4), a total of 83 (89.2%) patients recovered successfully and discharged, 27 (29%) in the TCZ group and 56 (60.2%) in the CS group. Total 10 (10.8%) patients died, out of which 6 (6.5%) belonged to the TCZ group and 4 (4.3%) belonged to the CS group The median Oxygen requirement with IQR was 8 (9) in both the groups and in total as well, p-value (0.714). CONCLUSIONS: Tocilizumab is a quite effective treatment option for critically sick patients of Covid-19 by reducing their oxygen requirement drastically and so the ICU stay, median hospital stay and so the mortality as well. CLINICALS TRIALS REGISTRATION: UIN # NCT04730323.

Frequency of foot ulcers in people with type 2 diabetes, presenting to specialist diabetes clinic at a Tertiary Care Hospital, Lahore, Pakistan.

BACKGROUND: Diabetic foot ulceration is a serious limb-threatening complication of diabetes. It is the common cause of hospital admissions and amputations. The objective of the study was to determine the prevalence of diabetic foot ulcers (DFU) and its association with age, gender, duration of diabetes, peripheral neuropathy (PN), peripheral arterial disease (PAD) and HbA1c. METHODS: A total of 1940 people (≥ 30 years of age) with type 2 diabetes coming to the Sakina Institute of Diabetes and Endocrine Research (specialist diabetes clinic) at Shalamar Hospital, Lahore, Pakistan, were recruited over a period of 1 year from January 2016 to January 2017. The foot ulcers were identified according to the University of Texas classification. PN was assessed by biothesiometer and PAD by ankle-brachial index (< 0.9). Body weight, height, body mass index (BMI), HbA1c and duration of diabetes were recorded. RESULTS: The prevalence of DFU was 7.02%, of which 4.5% of the ulcers were on the planter and 2.6% on the dorsal surface of the foot; 8.5% of the persons had bilateral foot ulcers and 0.4% subjects had Charcot deformity. There was significant association of foot ulcers with age, duration of diabetes, HbA1c, PN and PAD, whereas no association was observed with gender and BMI. PN and PAD were observed in 26.3 and 6.68% of people with diabetes respectively. Neuropathic ulcers and neuro-ischemic ulcers were identified in 74 and 19% of the study population. Logistic regression analysis revealed significant odds ratio for peripheral neuropathy 23.9 (95% confidence interval (5.41-105.6). CONCLUSIONS: Peripheral neuropathy is the commonest cause of foot ulcers. An optimum control of blood glucose to prevent neuropathy and regular feet examination of every person with diabetes may go a long way in preventing foot ulceration.

Impact of type 2 diabetes mellitus on quality of life in people with diabetespresenting to a specialist diabetes clinic.

BACKGROUND/AIM: Quality of life is an important health-related factor that has an impact on all health interventions. The aim of the study was to assess psychosocial outcomes in people with diabetes. MATERIALS AND METHODS: A total of 142 people with type 2 diabetes were recruited from a specialist diabetes center. The validated Urdu version of the WHO-5 Well-Being Index was administered for easy understanding of the quality of life of the regional population. RESULTS: The 142 adult participants with diabetes were recruited from a specialist diabetes clinic. The rate of likely depression (WHO-5 score of <28) was 16.9%. Neuropathy was found to have a negative impact on the quality of life in people with diabetes (P < 0.001). CONCLUSION: People with complications of diabetes like neuropathy may experience worsening quality of life. It is advised to incorporate the WHO-5 into annual patient reviews as a measure of emotional well-being to drive changes that improve outcomes for people with diabetes.

Pattern of physical activity among persons with type 2 diabetes with special consideration to daily routine.

OBJECTIVE: Physical activity is essential in maintaining a healthy lifestyle. Physical activity can improve general health, quality of life and diabetes management. The aim and objective of the study was to assess the physical activity trends in daily routine of people with type 2 diabetes. METHODS: Two hundred persons with diabetes from four different clinical settings were included to access the trends of physical activity using a customized questionnaire EPIC-2. Pattern of physical activity was assessed across a set of domains including sleep time, hours of TV watch, preferred mode of transport for specific distance and household activities. Data was analyzed using SPSS 21. RESULTS: Out of 200 persons with diabetes, 104(52%) were male and 96 (48%) were female. Out of the total sample of patients, 85 (81.7%) Male and 80 (83.3%) female patients preferred walk to cover a distance of less than one mile. There was a significant difference in selection of mode of transport for all other specified distance, esp. in female patients with both age groups. There was insignificant difference for physical activity pattern related to household activities in young and elderly male subjects. The mean sleeping time for younger male subjects on weekend was 464.31± 88.88 minutes/day and for elder it was 418.65± 102.66 minutes/day while for young female subjects was 476.25± 113.74 minutes/day and in female elderly subjects it was 420.62± 120.62 minutes/day respectively. CONCLUSION: In type 2 diabetics we observed a low level of physical activity which may be detrimental for the control of diabetes mellitus.

Fulminant hepatic failure (FHF) due to acute hepatitis C.

Acute hepatitis C (HCV) infection has been identified as an important cause of fulminant hepatic failure (FHF), characterized by rapid deterioration of liver function from massive hepatic necrosis leading to encephalopathy and multi-organ failure. We admitted a female patient at Shalamar Hospital with jaundice, fever, encephalopathy and coagulopathy of short duration with no history of any comorbidity. Her hepatitis viral screen revealed positive anti HCV. Her viral loads were also high. A diagnosis of FHF due to acute HCV infection was made. Patient was treated conservatively and improved gradually. In summary, acute HCV can cause FHF and should be ruled out in patients with FHF of unknown cause in an endemic country for HCV like Pakistan.

Charcot osteoarthropathy in type 2 diabetes persons presenting to specialist diabetes clinic at a tertiary care hospital.

BACKGROUND: Charcot osteoarthropathy or charcot foot is a rare, chronic, non-communicable condition of bones and joints which may results into severe deformity and more prone to develop ulcers possibly leading to amputation. The purpose of this study was to determine the prevalence of Charcot osteoarthropathy and its association with age, BMI, gender, duration of diabetes, HBA1c and peripheral neuropathy. METHODS: A total of 1931 subjects with type 2 diabetes having mean age 50.72 ± 10.66 years presenting in a specialist diabetes clinic at shalamar hospital, Lahore, Pakistan were enrolled. The diagnosis of Charcot osteoarthropathy was made by examination of both dorsal and plantar surfaces of foot for swelling, erythema, increase in temperature and any musculoskeletal deformity which was later confirmed by radiographs. Assessment of neuropathy was carried out by checking the sense of pressure, joint position and vibration. BMI (Body Mass Index), fasting blood glucose (FBG) and HbA1C were determined. RESULTS: In all subjects including male 704 (36.45 %) and female 1227 (63.55 %), 0.4 % subjects had charcot deformity, while 0.2 %, 0.15 % and 0.05 % subjects having right, left and bilateral deformity respectively. Bilaterally symmetrical neuropathy was diagnosed in 25.4 % in subjects. There was a significant association (p < 0.05) of deformity with duration of diabetes, HbA1C and neuropathy, however no significant association (p > 0.05) was found with age, BMI, weight, height and gender. CONCLUSION: There is a need to have a special care of persons with diabetes regarding blood glucose control and development of peripheral neuropathy. Early identification and management of risk factors may prevent the occurrence of charcot deformity. Patients must be educated about the foot care.