Efficacy and Safety of a Fixed-Dose Combination of Vildagliptin and Pioglitazone in Indian Patients With Type 2 Diabetes Mellitus: A Randomized, Open-Label, Comparative, Phase III Study.

Background Type 2 diabetes mellitus (T2DM) arises due to a range of pathological abnormalities, necessitating a combination therapy to achieve optimal glycemic control. Vildagliptin, an effective and selective DPP-4 inhibitor, and pioglitazone, an insulin sensitizer, offer distinct mechanisms of action. Hence, the integration of these medications represents a logical and justified therapeutic strategy Objective To compare the efficacy, safety, and tolerability of vildagliptin and pioglitazone 50 mg/15 mg fixed-dose combination (FDC) tablets with individual monotherapy vildagliptin 50 mg and pioglitazone 15 mg tablets in Indian T2DM patients who were inadequately controlled on metformin monotherapy. Methods This was a randomized, open-label, comparative, multicenter, phase III study involving 195 T2DM patients with inadequate glycemic control on metformin ≥ 1000 mg/day. Patients were randomly assigned in a 1:1:1 ratio to the test product group (n=65) (vildagliptin 50 mg + pioglitazone 15 mg FDC tablets), reference product group 1 (n=65) (vildagliptin 50 mg tablet), or reference product group 2 (n=65) (pioglitazone 15 mg tablet reference product). The primary endpoint was the mean change in HbA1c levels from baseline to end of the study visit (12 weeks (84 days ±2)). The secondary endpoints were the mean change in fasting plasma glucose (FPG) and 2-hr postprandial plasma glucose (2-hr PPG) levels. Safety parameters were assessed till the end of the study. Results A total of 178 patients completed the study. At 12 weeks, the mean HbA1c level in the test group reduced to 6.85 ± 1.27%, in the reference product 1 group to 7.56 ± 1.72%, and in the reference product 2 groups to 7.37 ± 1.59%. The mean change in Hb1Ac from baseline in the test group was statistically significant compared to the reference groups (p=0.037). Similarly, the mean changes in the FPG and 2hr-PPG with the test product were statistically significant compared to reference products (p=0.041). The adverse events were comparable across all the treatment groups. Conclusion In Indian T2DM patients inadequately controlled on a daily maximum dose of metformin, treatment with vildagliptin and pioglitazone FDC showed better glycemic control than either vildagliptin or pioglitazone along with a good tolerability profile.

Collagenofibrotic Glomerulopathy: Report a Rare Case.

Collagenofibrotic glomerulopathy is a rare clinical entity with fewer than 40 cases reported worldwide. We describe a case of adult onset nephrotic syndrome with partial villous atrophy of the intestine who was diagnosed with this rare entity. Collagenofibrotic glomerulopathy is characterized by subendothelial and mesangial collagen type III deposition and increased procollagen III peptide levels. Extra renal involvement has been described in the form of hypertension, anemia and microangiopathic hemolytic anemia but villous atrophy has not been associated with this condition so far, possibly reflecting the paucity of literature. We describe this case and review the condition in this report.

Askin (PNET) Tumor Unmasked by Trauma in a Young Male Patient.

A young male labourer developed pain at the site of blunt trauma over back of chest followed by fever, cough with expectoration, breathlessness and hemorrhagic pleural effusion in the side of injury. What could have been passed as a sequel of trauma turned out to be the consequences of an underlying rare and aggressive malignant tumor of the chest wall known as Askin tumor or Primitive Neuroectodermal Tumor (PNET). CT thorax with guided FNAC, debulking operation, histopathological examination followed by immunohistochemistry of the tumor tissue led to the final diagnosis. Chemotherapy was administered following surgical resection. The patient died within nine months after diagnosis.

Quadriparesis due to Gitelman's syndrome diagnosed with thiazide diuretic test response.

Gitelman's syndrome is characterized by hypocalciuria, severe hypomagnesemia, and prominent muscular involvements such as fatigue, weakness, cramps, and tetany. It is due to mutations in the thiazide sensitive NaCl co-transporter in the distal convoluted tubule. The administration of thiazide diuretics may induce a subnormal increase of urinary Cl(-) excretion in patients with Gitelman's syndrome, consistent with the hypothesis that less than normal Cl(-) is reabsorbed by the thiazide-inhibitable transporter in Gitelman's syndrome. Thus, we report a case of Gitelman's syndrome presenting with quadriparesis diagnosed by using thiazide clearance test.

An uncommon initial presentation of snake bite-subarachnoid hemorrhage: A case report with literature review.

Snake bites are very common in India, particularly in West Bengal. Snake bite can cause various hematological, neuromyopathical complications. It can be very fatal if not detected and treated early. Timely intervention can save the patient. We are reporting a case of hematotoxic Russell viper snake bite presented with subarachnoid hemorrhage. Patient was successfully treated with antivenom serum (AVS) along with other conservative management. Subarachnoid hemorrhage as an initial presentation in viper bite is very rare and we discuss the case with proper literature review.

Digital Gangrene an Unusual Presentation of Takayasu's Arteritis.

CONTEXT: Takayasu arteritis (TA) is a chronic inflammatory disease involving large vessels like aorta and its major branches. It presents to clinician with features of arm claudication, stroke, asymmetrical pulse, or asymmetrical blood pressure in both limbs. Digital gangrene may be occurred secondary to various systemic diseases like diabetes, thrombophilic states, vascular embolism, and medium and small vessel vasculitis or infections. Through evaluation to diagnose the exact etiology and timely intervention is needed to prevent progression of the gangrene which at the time can be life-threatening. Digital gangrene as an initial presentation in TA is very rare. In medical literature, there are only few case reports have been reported. CASE REPORT: We are reporting a case of a 26-year-old female patient presented with right little finger and index finger gangrene, ultimately diagnosed as TA and responded dramatically to treatment. CONCLUSION: Though rare, TA should be taken in the differential diagnosis for work up in a case of digital gangrene and it necessitates more studies in this field to uncover the exact pathophysiology for such presentation.

A rare cause of seizures, parkinsonian, and cerebellar signs: brain calcinosis secondary to thyroidectomy.

CONTEXT: Post-thyroidectomy hypoparathyroidism presenting with Parkinsonian features and seizures with extensive intracranial calcifications is uncommon. Acquired intracranial calcification that affects structures other than the basal ganglia is rare. CASE REPORT: We report a case of a 45-year-old woman with a history of total thyroidectomy who presented with Parkinsonian features, cerebellar signs, and seizures. Brain imaging revealed extensive intracranial calcifications secondary to long-standing hypoparathyroidism. The patient was treated with intravenous (IV) calcium gluconate therapy and shifted to oral calcium and calcitriol therapy. Her symptoms improved markedly. At four months of follow up, the patient had not suffered another episode of seizure and was being gradually weaned off anti-Parkinsonian therapy. CONCLUSION: This case describes the rare finding of extensive intracranial calcifications in a case of iatrogenic hypoparathyroidism secondary to thyroidectomy with its wide array of features and its remarkable response to restoration of calcium levels to normal limits.

Type II lepra reaction--an unusual presentation.

Type II lepra reaction usually present with skin lesions. We report a 23 years old male patient presented with fever for two weeks with no visible skin lesion suggestive of leprosy and with no history of either completion or concurrent anti leprosy drug treatment was eventually turned out to be a case of Hansen's presenting with type II lepra reaction.

42 years old male with single atrium.

Single atrium (SA) is a rare congenital anomaly characterized by absence or virtual absence of atrial septum, vestigial remnant of which occasionally remain. We report here such a case of SA who presents his symptoms in different way of its natural course of presentation.

Cystathionine beta-synthase T833C/844INS68 polymorphism: a family-based study on mentally retarded children.

BACKGROUND: Cystathionine beta-synthase (CBS) mediates conversion of homocysteine to cystathionine and deficiency in enzyme activity may lead to hyperhomocysteinemia/homocystinuria, which are often associated with mental retardation (MR). A large number of polymorphisms have been reported in the CBS gene, some of which impair its activity and among these, a T833C polymorphism in cis with a 68 bp insertion at 844 in the exon 8 is found to be associated with mild hyperhomocysteinemia in different ethnic groups. METHODS: The present study is aimed at investigating the association between T833C/844ins68 polymorphism and MR. One hundred and ninety MR cases were recruited after psychometric evaluation. Hundred and thirty-eight control subjects, two hundred and sixty-seven parents of MR probands and thirty cardiovascular disorder (CVD) patients were included for comparison. Peripheral blood was collected after obtaining informed written consent. The T833C/844ins68 polymorphism was investigated by PCR amplification of genomic DNA and restriction fragment length polymorphism analysis, followed by statistical analysis. RESULTS: The genotypic distribution of the polymorphism was within the Hardy-Weinberg equilibrium. A slightly increased genotypic frequency was observed in the Indian control population as compared to other Asian populations. Both haplotype-based haplotype relative risk analysis and transmission disequilibrium test reveled lack of association of the T833C/844ins68 polymorphism with MR; nevertheless, the relative risk calculated was higher (>1) and in a limited number of informative MR families, preferential transmission of the double mutant from heterozygous mothers to the MR probands was noticed (chi2 = 4.00, P < 0.05). CONCLUSION: This is the first molecular genetic study of CBS gene dealing with T833C/844ins68 double mutation in MR subjects. Our preliminary data indicate lack of association between T833C/844ins68 polymorphism with MR. However, higher relative risk and biased transmission of the double mutation from heterozygous mothers to MR probands are indicative of a risk of association between this polymorphism with mental retardation.

Role of clinical biochemistry laboratory in the diagnosis of diabetes mellitus.

Clinical biochemistry and laboratory help is needed at all stages of diagnosis of diabetes. Laboratory plays a key role in the management of diabetes and its complications like renal, metabolic, and others. Monitoring of treatment is also guided by regular blood sugar estimation and self-monitoring of blood glucose level.