Comparative effectiveness of sitagliptin and vildagliptin in the management of patients with type 2 diabetes mellitus undergoing haemodialysis: an Indian rural tertiary care centre experience

Background: The prevalence of chronic kidney disease is increasing with diabetic nephropathy as the common underlying cause. Although numerous drugs are being used to improve glycaemic control, evidence in patients with diabetic nephropathy is sparse. The aim of the present was to evaluate the effectiveness of sitagliptin or vildagliptin addition on glycaemic control in patients with T2DM undergoing haemodialysis as part of their routine care in a rural tertiary care setting.Methods: Type 2 diabetic patients on maintenance haemodialysis as part of routine care and whose glycaemia was not controlled adequately and prescribed one of the oral gliptins once daily in addition to existing therapy for a period of 24 weeks were included in the present study. Effectiveness was assessed in terms of glycaemic control as measured by the change over time in glycated haemoglobin. Data analysis included glycated haemoglobin, body weight, serum creatinine, urine albumin creatinine ratio and the occurrence of hypoglycaemia.Results: Significant reduction in glycated haemoglobin values were noted after 24 weeks of therapy with gliptins similar to insulin glargine with a small weight loss. There was an insignificant decrease in the serum creatinine and urine albumin excretion levels after treatment with vildagliptin with Vildagliptin producing a slightly higher decrease but there was no correlation with changes in A1c levels. The overall incidence of adverse experiences was low and generally mild in both groups.Conclusions: In a group of Asian Indian patients with diabetic nephropathy due to T2DM undergoing haemodialysis in whom glycaemia was not controlled adequately, addition of gliptins helped to achieve glycaemic control to a similar extent as insulin glargine but with a marginal weight advantage

Evaluation of analgesic and anti-inflammatory activity of a combination of tramadol-pregabalin in animal models of pain and inflammation

Background: A major goal of pain management is to provide pain relief that is clinically meaningful, sustained, and associated with minimum and reversible adverse effects. Since single analgesic drug is not effective in all patients, there is a need either to develop new and more effective drugs or to identify favourable combinations of drugs that are already available. The aim of the present was to evaluate the analgesic and anti-inflammatory activity of tramadol and pregabalin when used alone or in combination in animal models of pain and inflammation.Methods: The animals (rats and mice) were divided into eight groups with six animals in each group. Analgesia was assessed by acetic acid induced writhing and tail flick methods in mice and hot plate method in rats. Paw oedema model in rats after induction with 0.1 ml of 1% carrageenan was used to assess the anti‑inflammatory activity. The percentage inhibition of writhes and prolongation of reaction time were used for assessing analgesic activity and reduction in paw volume was used for assessing anti-inflammatory activity. The results obtained were analysed by ANOVA and Tukey HSD Post-hoc Test.Results: Treatment with tramadol pregabalin alone or in combination reduced writhing episodes significantly in acetic acid induced writhing in mice as compared to control indicating its analgesic effect and the highest percentage inhibition of pain was seen with high dose tramadol plus pregabalin. Treatment in Hot plate and Tail flick methods significantly prolonged the reaction time at all time points.Conclusions: Tramadol when combined with pregabalin may enhance its anti-nociceptive effects. If confirmed in additional models of acute and/or chronic pain this combination might be useful in the clinical management of pain not associated with inflammation

Multiple Intravenous Administrations of Human Umbilical Cord Blood Cells Benefit in a Mouse Model of ALS

Background: A promising therapeutic strategy for amyotrophic lateral sclerosis (ALS) is the use of cell-based therapies that can protect motor neurons and thereby retard disease progression. We recently showed that a single large dose (25x10(6) cells) of mononuclear cells from human umbilical cord blood (MNC hUCB) administered intravenously to pre-symptomatic G93A SOD1 mice is optimal in delaying disease progression and increasing lifespan. However, this single high cell dose is impractical for clinical use. The aim of the present pre-clinical translation study was therefore to evaluate the effects of multiple low dose systemic injections of MNC hUCB cell into G93A SOD1 mice at different disease stages. Methodology/Principal Findings: Mice received weekly intravenous injections of MNC hUCB or media. Symptomatic mice received 10(6) or 2.5x10(6) cells from 13 weeks of age. A third, pre-symptomatic, group received 10(6) cells from 9 weeks of age. Control groups were media-injected G93A and mice carrying the normal hSOD1 gene. Motor function tests and various assays determined cell effects. Administered cell distribution, motor neuron counts, and glial cell densities were analyzed in mouse spinal cords. Results showed that mice receiving 10(6) cells pre-symptomatically or 2.5x10(6) cells symptomatically significantly delayed functional deterioration, increased lifespan and had higher motor neuron counts than media mice. Astrocytes and microglia were significantly reduced in all cell-treated groups. Conclusions/Significance: These results demonstrate that multiple injections of MNC hUCB cells, even beginning at the symptomatic disease stage, could benefit disease outcomes by protecting motor neurons from inflammatory effectors. This multiple cell infusion approach may promote future clinical studies

Comparative effectiveness of sitagliptin and vildagliptin in the management of patients with type 2 diabetes mellitus undergoing haemodialysis: an Indian rural tertiary care centre experience

Background: The prevalence of chronic kidney disease is increasing with diabetic nephropathy as the common underlying cause. Although numerous drugs are being used to improve glycaemic control, evidence in patients with diabetic nephropathy is sparse. The aim of the present was to evaluate the effectiveness of sitagliptin or vildagliptin addition on glycaemic control in patients with T2DM undergoing haemodialysis as part of their routine care in a rural tertiary care setting.Methods: Type 2 diabetic patients on maintenance haemodialysis as part of routine care and whose glycaemia was not controlled adequately and prescribed one of the oral gliptins once daily in addition to existing therapy for a period of 24 weeks were included in the present study. Effectiveness was assessed in terms of glycaemic control as measured by the change over time in glycated haemoglobin. Data analysis included glycated haemoglobin, body weight, serum creatinine, urine albumin creatinine ratio and the occurrence of hypoglycaemia.Results: Significant reduction in glycated haemoglobin values were noted after 24 weeks of therapy with gliptins similar to insulin glargine with a small weight loss. There was an insignificant decrease in the serum creatinine and urine albumin excretion levels after treatment with vildagliptin with Vildagliptin producing a slightly higher decrease but there was no correlation with changes in A1c levels. The overall incidence of adverse experiences was low and generally mild in both groups.Conclusions: In a group of Asian Indian patients with diabetic nephropathy due to T2DM undergoing haemodialysis in whom glycaemia was not controlled adequately, addition of gliptins helped to achieve glycaemic control to a similar extent as insulin glargine but with a marginal weight advantage

Body composition assessment by artificial intelligence can be a predictive tool for short-term postoperative complications in Hartmann’s reversals

Abstract Background Hartmann's reversal, a complex elective surgery, reverses and closes the colostomy in individuals who previously underwent a Hartmann's procedure due to colonic pathology like cancer or diverticulitis. It demands careful planning and patient optimisation to help reduce postoperative complications. Preoperative evaluation of body composition has been useful in identifying patients at high risk of short-term postoperative outcomes following colorectal cancer surgery. We sought to explore the use of our in-house derived Artificial Intelligence (AI) algorithm to measure body composition within patients undergoing Hartmann’s reversal procedure in the prediction of short-term postoperative complications. Methods A retrospective study of all patients who underwent Hartmann's reversal within a single tertiary referral centre (Western) in Melbourne, Australia and who had a preoperative Computerised Tomography (CT) scan performed. Body composition was measured using our previously validated AI algorithm for body segmentation developed by the Department of Surgery, Western Precinct, University of Melbourne. Sarcopenia in our study was defined as a skeletal muscle index (SMI), calculated as Skeletal Muscle Area (SMA) /height2 < 38.5 cm2/m2 in women and < 52.4 cm2/m2 in men. Results Between 2010 and 2020, 47 patients (mean age 63.1 ± 12.3 years; male, n = 28 (59.6%) underwent body composition analysis. Twenty-one patients (44.7%) were sarcopenic, and 12 (25.5%) had evidence of sarcopenic obesity. The most common postoperative complication was surgical site infection (SSI) (n = 8, 17%). Sarcopenia (n = 7, 87.5%, p = 0.02) and sarcopenic obesity (n = 5, 62.5%, p = 0.02) were significantly associated with SSIs. The risks of developing an SSI were 8.7 times greater when sarcopenia was present. Conclusion Sarcopenia and sarcopenic obesity were related to postoperative complications following Hartmann’s reversal. Body composition measured by a validated AI algorithm may be a beneficial tool for predicting short-term surgical outcomes for these patients

Additional file 1 of Body composition assessment by artificial intelligence can be a predictive tool for short-term postoperative complications in Hartmann’s reversals

Supplementary Material 1

Evaluations of disease progression in G93A mice through Kaplan-Meier analysis.

<p>(<b>A</b>) Time elapsed until animals lost 15% of their maximum body weight. Mice receiving 1×10⁶ cells pre-symptomatically (<i>Gr 3</i>) significantly () maintained body weight vs. Media (<i>Gr 4</i>) mice. A similar trend was observed in mice treated with 2.5×10⁶ cells (<i>Gr 1</i>) beginning at symptomatic disease stage. (<b>B</b>) Time elapsed until hindlimb extension scores deteriorated by 70% of the initial score. The <i>Gr 1</i> and <i>Gr 3</i> mice significantly () delayed decline of hindlimb extension compared to <i>Gr 4</i> mice. A significant difference was also detected between <i>Gr 3</i> and <i>Gr 2</i> mice receiving 1×10⁶ cells at pre-symptomatic or symptomatic stage of disease, respectively. (<b>C</b>) Time elapsed until muscle strength decreased by 70% from the maximum value. Mice from <i>Gr 3</i> significantly () delayed muscle strength losses vs. <i>Gr 4</i>. <i>Gr 1</i> mice tended to maintain muscle strength post-transplant. (<b>D</b>) Time elapsed until rotarod latency decreased by 70% of the maximum value. Only mice from <i>Gr 3</i> performed better on the rotarod than other cell-treated mice and tended towards significance () taking more time to decrease latency by over 70% of the maximum value compared to <i>Gr 4</i>.</p

Characteristics of microglial cells in the spinal cords of G93A mice.

<p>Microglial densities were measured in the cervical (<b>A</b>) and lumbar (<b>B</b>) ventral horns of G93A mice at 17 weeks of age and at end-stage of disease. Microglial densities were significantly (p<0.001) higher in Media-injected mice (<i>Gr 4</i>) compared to control mice (<i>Gr 5</i>) of the same ages. MNC hUCB cell administrations significantly (p<0.001) decreased the number of microglia in the spinal cord of G93A mice compared to Media mice. No significant differences were detected between the cell-treated groups. *p<0.05, **p<0.01, ***p<0.001. (<b>C</b>) Immunohistochemical staining of microglia in the lumbar spinal cord at 17 weeks of age. Microglial cells stained for anti-Iba-1 antibody were sparse in controls (<b>a</b>) and microgliosis was noted in Media-treated animals (<b>b</b>). MNC hUCB cells decreased microglial density in mice from <i>Gr 1</i> (<b>c</b>), <i>Gr 2</i> (<b>d</b>), and <i>Gr 3</i> (<b>e</b>). Morphological analysis of microglial cells determined numerous activated cells with large cell bodies and short processes in Media-injected mice, whereas ramified microglia were mostly observed in cell-treated animals, particularly in <i>Gr 1</i> and <i>Gr 3</i> mice and controls (inserts in a–e). Scale bar: a–e is 200 µm; in a–e inserts is 25 µm.</p