Acute myeloid leukemia in a young male patient with Behçet's disease presenting with febrile neutropenia.

Behçet's disease is a multi-systemic vasculitis which is characterized by recurrent oral and genital ulceration with positive pathergy test. These features may also be seen in various hematological malignancies. In patients with leukemia who present with Behçet's disease-like features, it is often difficult to ascertain whether the clinical manifestations are due to leukemia, or there is co-existing Behçet's disease too. The authors report an Indian farmer who presented with clinical features suggestive of Behçet's disease with profound neutropenia. On bone marrow examination he was found to have acute monocytic leukemia (AML-M5). Chemotherapy for leukemia did not relieve his oral and genital ulcers, for which glucocorticoids and colchicine had to be given. So the patient had co-existence of Behçet's disease along with AML-M5, which has never been reported in the literature before.

Adult Onset Still's Disease Masquerading as Sepsis in an Asplenic Patient.

Adult onset Still's disease (AOSD) is a rare inflammatory disorder of unknown etiology. It is a diagnosis of exclusion. We report a case of post-splenectomised man, presented with high grade fever, joint pain and body ache. Since Overwhelming Post Splenectomy Infection (OPSI) was the initial probable diagnosis, empirical antibiotic therapy was initiated. Evaluation to find a septic focus, autoimmune diseases ad malignancies was carried out which showed negative results. Since alternative diagnoses were excluded and the Yamaguchi's criteria for AOSD was fulfilled, the patient was treated with IV steroids which resulted in rapid resolution of his symptoms. AOSD with asplenia is a unique condition because immunosuppressive therapy for AOSD may increase the risk of OPSI in such a patient. This is the first case report of AOSD in an asplenic patient from India.

Fixed-Dose Combination of Dapagliflozin + Sitagliptin + Metformin in Patients with Type 2 Diabetes Poorly Controlled with Metformin: Phase 3, Randomized Comparison with Dual Combinations.

INTRODUCTION: This study compared efficacy and safety of triple drug fixed-dose combination (FDC) of dapagliflozin (DAPA) + sitagliptin (SITA) + metformin (MET) extended release (ER) with SITA + MET sustained release (SR) and DAPA + MET ER in patients with type 2 diabetes poorly controlled with metformin. METHODS: This phase 3, randomized, open-label, active-controlled study included adult patients with glycated hemoglobin (HbA1c) ≥ 8% (64 mmol/mol) and ≤ 11% (97 mmol/mol), randomized in 1:1:1 ratio to receive either FDC of DAPA + SITA + MET ER (10 mg + 100 mg + 1000 mg) tablets once daily (n = 137) or co-administration of SITA + MET SR (100 mg + 1000 mg) tablets once daily (n = 139) or FDC of DAPA + MET ER (10 mg + 1000 mg) tablets once daily (n = 139). Primary endpoint was mean change in HbA1c from baseline to week 16. RESULTS: Mean baseline HbA1c was approximately 9% (75 mmol/mol) in each treatment group. At week 16, adjusted mean reduction in HbA1c from baseline was significantly greater with DAPA + SITA + MET ER (- 1.73% [- 19.0 mmol/mol]) compared to SITA + MET SR (- 1.28% [- 14.1 mmol/mol]; difference of - 0.46% [- 5.1 mmol/mol], p < 0.001) and DAPA + MET ER (- 1.33% [- 14.6 mmol/mol]; difference - 0.4% [4.4 mmol/mol], p < 0.001). Similarly, at week 12, reduction in HbA1c from baseline was significantly greater with DAPA + SITA + MET ER compared to SITA + MET SR (p = 0.0006) and DAPA + MET ER (p = 0.0276). At week 16, DAPA + SITA + MET ER showed significant reduction in postprandial blood glucose compared to DAPA + MET ER (p = 0.0394) and significant reduction in fasting blood glucose with DAPA + SITA + MET ER compared to SITA + MET SR (p = 0.0226). The proportion of patients achieving HbA1c < 7.0% (53 mmol/mol) at week 16 was significantly higher with DAPA + SITA + MET ER (38.5%) versus SITA + MET SR (12.8%) (p < 0.001) and DAPA + MET ER (21.3%) (p = 0.0023). All study medications were well tolerated. CONCLUSION: Triple FDC of DAPA + SITA + MET ER tablets once daily was significantly better in achieving glycemic control versus dual combination once daily in patients with type 2 diabetes poorly controlled with metformin without any significant safety concerns. TRIAL REGISTRATION: CTRI/2021/11/038176, registered on 22 November 2021.

Type 2 diabetes is a progressive disease in which the risks of microvascular and macrovascular complications and mortality are strongly associated with hyperglycemia. Achieving glycemic control remains the main goal of treatment to prevent these complications. Estimates in 2019 showed that 77 million individuals had diabetes in India, which is expected to rise over 134 million by 2045. Considering the progressive nature of the disease, many guidelines recommend use of dual or triple drug therapy based on glycated hemoglobin (HbA1c) level. Use of fixed-dose combination (FDC) helps to improve therapy compliance and can provide optimum therapeutic benefits. Mechanisms of action of dipeptidyl peptidase 4 (DPP4) and sodium­glucose cotransporter 2 (SGLT2) inhibitors are complementary to that of metformin with low risk of hypoglycemia. Studies have shown beneficial effects of adding both DPP4 inhibitors and SGLT2 inhibitors after metformin monotherapy. This phase 3 study was designed to assess efficacy and safety of triple FDC of dapagliflozin + sitagliptin + metformin extended release in comparison with combipack of sitagliptin + metformin sustained release and FDC of dapagliflozin + metformin ER in patients with type 2 diabetes inadequately controlled with metformin monotherapy. The study demonstrated superiority of triple FDC of dapagliflozin + sitagliptin + metformin ER over dual combinations in terms of reduction in HbA1c and percentage of patients achieving target HbA1c at the end of week 16. The current study provides evidence for considering triple FDC of dapagliflozin + sitagliptin + metformin ER as an alternative option with minimal risk of hypoglycemia and weight gain, while considering oral triple-combination therapy for patients to achieve their glycemic target.

Prevalence of peripheral arterial disease in type 2 diabetes mellitus and its correlation with coronary artery disease and its risk factors.

OBJECTIVES: Peripheral arterial disease (PAD) is one of the macrovascular complications of type 2 diabetes mellitus. Unlike other complications, it has received little attention in the Indian medical literature. There is significant difference in the reported prevalence of PAD and its associated risk factors between Indian and Western studies. In order to assess PAD in diabetics, its associated risk factors and its relationship with coronary artery disease, we conducted a hospital-based, cross-sectional study. METHODS: Consecutive patients on regular follow up in our diabetes clinic were included. In addition to a detailed history and physical examination, anthropometric parameters like body mass index, waist circumference and waist hip ratio were measured. Relevant laboratory investigations were performed. Modified Rose questionnaire and Minnesota codes were used to diagnose coronary artery disease (CAD). Colour Doppler examination of the arteries of the lower limbs was performed. Arteries were evaluated both longitudinally and transversely. Individual ABI was obtained for each leg by dividing corresponding ankle pressure by the brachial pressure. The lower of the values obtained for the two legs was taken as the true ABI. A cut off of < 0.9 was used to define peripheral arterial disease. Predictors of PAD were assessed using univariate tests of significance. Binary logistic regression was used to identify independent predictors of CAD. RESULTS: We studied 146 patients (79 men and 67 women; mean age 59.4 +/- 7.2 years; mean duration of diabetes 8.8 +/- 3.8 years). The prevalence of PAD was 14.4% with women having a slightly higher prevalence (14.9%), as compared to men (13.9%) (p=0.864). CAD was present in 28%. Age, duration of diabetes, smoking, systolic and diastolic blood pressures and an HbA1c >7% were significant predictors of PAD. We did not find a correlation between measures of obesity and PAD. Using binary logistic regression, older age (p=0.01), higher HbA1c levels (p=0.02), microalbuminuria (p=0.03) and deranged lipid profile (total cholesterol, HDL, triglycerides) were found to be significant predictors of CAD. CONCLUSION: Using ankle brachial index, we found evidence of PAD in 14.3% of type 2 diabetics. Risk factors significantly associated with PAD were--higher age, longer duration of diabetes, higher systolic and diastolic blood pressure, smoking, higher HbA1c levels and CAD. The prevalence of CAD was higher in patients with PAD (52.38% vs. 24% in those without PAD; p=0.007). Thus the presence of PAD should alert the clinician to a high probability of underlying CAD.

Prevalence of non-alcoholic fatty liver disease and its correlation with coronary risk factors in patients with type 2 diabetes.

OBJECTIVES: To estimate the prevalence of non-alcoholic fatty liver disease (NAFLD) by ultrasonography, and to correlate NAFLD with coronary artery disease (CAD) and coronary risk factors in a group of Indian type 2 diabetics. METHODS: Consecutive patients of type 2 diabetes were recruited. History and physical examination were recorded. Laboratory investigations included fasting and 2-hour post-prandial blood glucose, blood urea, serum creatinine, liver function tests, lipid profile, glycated haemoglobin, microalbuminuria, and ultrasonographic measurement of carotid intimal-medial thickness (CIMT). NAFLD was diagnosed on the basis of ultrasound assessment of the liver. RESULTS: The study group (n=124) was divided into a NAFLD group (n=71) and a non-NAFLD group (n=53). The prevalence of NAFLD was 57.2%. CAD was more prevalent in the NAFLD subgroup (60.5%) compared to the non-NAFLD subgroup (45.2%). The NAFLD subgroup had higher prevalence of hypertension, smoking, obesity (measured by BMI), central obesity (measured by waist circumference and waist hip ratio), higher HbAlc, higher triglyceride levels and lower HDL levels, and higher mean CIMT. Using binary logistic regression analysis, it was found that hypertension (p=0.013), LDL cholesterol (p=0.049), microalbuminuria (p=0.034) and NAFLD (p=0.016) were significantly correlated with CAD. CONCLUSION: Among type 2 diabetics, NAFLD clusters with traditional coronary risk factors. It is a surrogate and fairly reliable marker of risk for CAD amongst type 2 diabetic patients. Ultrasonographically detected NAFLD is a simple, cheap, and safely assessable parameter for coronary risk stratification in type 2 diabetics.

Data on vildagliptin and vildagliptin plus metformin combination in type-2 diabetes mellitus management.

It is of interest to evaluate the clinical effectiveness and safety of vildagliptin as monotherapy and combination therapy of vildagliptin and metformin for the management of type 2 diabetes mellitus (T2DM) patients in Indian settings. The study included patients with T2DM (aged >18 years) receiving vildagliptin monotherapy and vildagliptin in combination with metformin therapy of various strengths. Data related to demographics, risk factors, medical history, glycated hemoglobin (HbA1c) levels, and medical therapies were retrieved from medical records. Out of 9678 patients (median age, 52.0 years), 59.1% were men. A combination of vildagliptin and metformin (50/500 mg) was the most commonly used therapy (54.8%), and the median duration of therapy was 24.0 months. The predominant reason for selecting vildagliptin therapy was to improve HbA1c levels (87.8%). A total of 87.5% of patients required dosage up-titration. Vildagliptin therapy was used in patients with T2DM and associated complications (peripheral neuropathy, CAD, nephropathy, retinopathy, autonomous neuropathy, stroke/TIA, and peripheral artery disease). Among 5175 patients who experienced body weight changes, a majority of patients showed a loss of weight (68.6%). The target glycemic control was achieved in 95.3% of patients. The mean HbA1c levels were significantly decreased post-treatment (mean change: 1.34%; p<0.001). Adverse events were reported in 0.4% of patients. Physicians rated the majority of patients as good to excellent on the global evaluation of efficacy and tolerability scale (98.9%, each). Vildagliptin as monotherapy and combination therapy of vildagliptin and metformin was an effective therapy in reducing HbA1c helps in achieving target glycemic control, and was well tolerated in Indian patients with T2DM continuum.

Clinical and laboratory factors associated with mortality in dengue.

Dengue is endemic in more than 100 countries, giving rise to an increased number of deaths in the last five years in the South-East Asian region. We report our findings from a retrospective study of adults admitted with confirmed dengue at our institution. We studied the clinical and laboratory parameters associated with mortality in these patients. Of the 172 hospitalised patients studied, 156 (90.69 %) recovered while 16 (9.3%) died. Univariate analysis showed altered sensorium on presentation, lower haemoglobin and haematocrit levels, higher serum creatinine, higher serum transaminase and lower serum albumin levels to be significantly associated with mortality in dengue. Further, using stepwise multivariate logistic regression, altered sensorium ( P = 0.006) and hypoalbuminemia ( P = 0.013) were identified as independent predictors of mortality in dengue. Identification of these parameters early in the course of disease should prompt intensification of treatment in dengue cases.