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- Disturbances of gastrointestinal transit and autonomic functions in postural orthostatic tachycardia syndrome. [JOURNAL ARTICLE]
- Neurogastroenterol Motil 2014 Dec 6.
Gastrointestinal symptoms are common in the postural orthostatic tachycardia syndrome (POTS). However, few studies have evaluated gastrointestinal transit in POTS. Our primary objectives were to evaluate gastrointestinal emptying and the relationship with autonomic dysfunctions in POTS.We reviewed the complete medical records of all patients aged 18 years and older with POTS diagnosed by a standardized autonomic reflex screen who also had a scintigraphic assessment of gastrointestinal transit at Mayo Clinic Rochester between 1998 and 2012. Associations between specific gastric emptying and autonomic (i.e., cardiovagal, adrenergic, and sudomotor) disturbances were evaluated.Among 163 patients (140 women, mean [±SEM] age 30 [±1] years), 55 (34%) had normal, 30 (18%) had delayed, and 78 (48%) had rapid gastric emptying. Fifty-eight patients (36%) had clinical features of physical deconditioning, which was associated (p = 0.02) with rapid gastric emptying. Associations with delayed gastric emptying included vomiting, which was more common (p < 0.003), and anxiety or depression, which was less common (p = 0.02). The tilt-associated increase in heart rate and reduction in systolic BP at 1 min was associated (p < 0.05), being greater in patients with delayed gastric emptying.Two-thirds of patients with POTS and GI symptoms had abnormal, most frequently rapid gastric emptying. Except for more severe adrenergic impairment in patients with delayed gastric emptying, the pattern of autonomic dysfunction did not discriminate among gastric emptying groups. Further studies are necessary to ascertain whether extravascular volume depletion and/or deconditioning contribute to POTS in patients with gastrointestinal symptoms.
- Follow-up after gastric electrical stimulation for gastroparesis. [Journal Article]
- J Am Coll Surg 2015 Jan; 220(1):57-63.
Gastric electrical stimulation (GES) is used to treat medically refractory gastroparesis. However, there are few large series with outcomes beyond 12 months. This study reports surgical outcomes of GES for patients up to 8 years receiving treatment from a single institution.A prospective database was reviewed from 2003 to 2013 for patients undergoing GES. Baseline patient characteristics were recorded, including age, sex, cause of gastroparesis, gastric emptying, and Hgb A1C. Outcomes variables included nutrition supplementation, additional operations, 30-day morbidity, and mortality. Pre- and postoperative pain and function scores are analyzed over time using generalized estimating equations. Patient outcomes in terms of reoperation rates and types of operations are also reviewed.Seventy-nine patients underwent GES with a mean ± SD age of 43 ± 11 years and a BMI of 27 ± 8 kg/m(2). Symptom scores were available for 60 patients: 60 patients at baseline, 52 patients at 1 year, 14 patients during years 2 to 3, and 18 patients during years 4 to 8. Symptom scores decreased considerably in all categories. At 1-year follow-up, 44% and 31% of patients had at least a 25% reduction in symptom distress for functional and pain symptoms, respectively. Preoperatively, 9 patients required nutrition supplementation. After implantation, 34 (43%) patients underwent additional operations, with a mean of 2.15 operations per patient. Generator-related causes were the most common indication for reoperation, including battery exchanges and relocation. Other operations included 8 gastrectomies and 7 median arcuate ligament releases. Postoperatively, 4 patients required supplemental nutrition. There were no 30-day mortalities, but 11 patients died during the study period.Gastric electrical stimulation was significantly associated with reductions in both functional and pain-related symptoms of gastroparesis. Patients who undergo GES have a high likelihood of additional surgery.
- Does the Emptier Have No Clothes? Diabetes, Gastric Emptying, and the Syndrome of Gastroparesis. [EDITORIAL]
- Clin Gastroenterol Hepatol 2014 Nov 6.
- Blockade of p38 mitogen-activated protein kinase pathway ameliorates delayed gastric emptying in streptozotocin-induced diabetic rats. [Journal Article]
- Int Immunopharmacol 2014 Dec; 23(2):696-700.
Gastrointestinal dysfunction is one of the major complications of diabetes. The roles of inflammation in diabetes and its associated complications are increasingly recognized. p38 mitogen-activated protein kinase (MAPK) has been shown to be involved in the production of pro-inflammatory mediators. The aims of this study were to investigate the effects of SB203580, a specific p38 MAPK inhibitor, on delayed gastric emptying in diabetic rats and to elucidate its possible mechanism.SB203580 was administered in diabetic rats induced by intraperitoneal injection of streptozotocin. The gastric emptying rate of rats was measured by using phenol red solution, and blood glucose levels and body weights were observed. p38 MAPK activity and iNOS expression were assessed by Western blot analysis. The expression of tumor necrosis factor (TNF)-α and interleukin (IL)-1β were determined by enzyme-linked immunosorbent assay.Gastric emptying was delayed significantly in diabetic rats and improved significantly with SB203580; high glucose significantly activated p38 MAPK and increased the expression of iNOS, TNF-α and IL-1β. The administration of SB203580 led to a significant decrease in the activation of p38 MAPK and the expression of iNOS, TNF-α and IL-1β.Inflammation was associated with the development of delayed gastric emptying, and blockade of p38 MAPK pathway with SB203580 ameliorates delayed gastric emptying in diabetic rats, at least in part, by inhibiting the expression of iNOS, TNF-a and IL-1β. Therefore, p38MAPK may serve as a novel target for the therapy of diabetes-related gastrointestinal dysmotility.
- Gastroparesis is common after lung transplantation and may be ameliorated by botulinum toxin-A injection of the pylorus. [Letter]
- J Heart Lung Transplant 2014 Dec; 33(12):1314-6.
- Gastric emptying and glycaemia in health and diabetes mellitus. [REVIEW]
- Nat Rev Endocrinol 2014 Nov 25.
The rate of gastric emptying is a critical determinant of postprandial glycaemia and, accordingly, is fundamental to maintaining blood glucose homeostasis. Disordered gastric emptying occurs frequently in patients with longstanding type 1 diabetes mellitus and type 2 diabetes mellitus (T2DM). A complex bidirectional relationship exists between gastric emptying and glycaemia-gastric emptying accounts for ∼35% of the variance in peak postprandial blood glucose concentrations in healthy individuals and in patients with diabetes mellitus, and the rate of emptying is itself modulated by acute changes in glycaemia. Clinical implementation of incretin-based therapies for the management of T2DM, which diminish postprandial glycaemia, in part by slowing gastric emptying, is widespread. Other therapies for patients with T2DM, which specifically target gastric emptying include pramlintide and dietary-based treatment approaches. A weak association exists between upper gastrointestinal symptoms and the rate of gastric emptying. In patients with severe diabetic gastroparesis, pathological changes are highly variable and are characterized by loss of interstitial cells of Cajal and an immune infiltrate. Management options for patients with symptomatic gastroparesis remain limited in their efficacy, which probably reflects the heterogeneous nature of the underlying pathophysiology.
- Microangiopathy is Common in Submucosal Vessels of the Colon in Patients With Diabetes Mellitus. [Journal Article]
- Rev Diabet Stud 2014; 11(2):175-80.
The pathophysiology behind gastrointestinal dysmotility in diabetes mellitus is unknown. Both esophageal dysmotility and gastroparesis have been shown to be associated with retinopathy, suggesting that microangiopathy is important in the common etiology. The aim of the present study was to examine whether patients with diabetes exhibit microangiopathy in the colon, and if present, to correlate microangiopathy with the clinical picture.Consecutive patients subjected to colon surgery were identified in the southernmost districts of Skåne between January 2011 and May 2013. Medical records were scrutinized, and patients with a history of diabetes were noted. Gender, age, type of diabetes, treatment, complications, and other concomitant diseases were registered. Histopathologic re-evaluation of surgical biopsies with morphometric analyses of submucosal vessels in the colon was performed. Morphometric examination and clinical data were compared with non-diabetic patients.Of 1135 identified patients during the time period studied, 95 patients with diabetes were recognized and included. Fifty-three non-diabetic, randomly chosen patients served as controls. The mean age was 71.8 ± 10.2 and 71.4 ± 9.5 years in diabetic and non-diabetic patients, respectively. Microangiopathy was found in 68.4% of diabetic patients and in 7.5% of non-diabetic patients (p < 0.001). The wall-to-lumen ratio was 0.31 (0.23-0.46) in patients with diabetes compared with 0.16 (0.12-0.21) in non-diabetic patients (p < 0.001). No clinical association with microangiopathy could be verified.Microangiopathy in the colon is more common in diabetic than in non-diabetic patients. The clinical significance of microangopathy has yet to be clarified.
- Effectiveness of gastric neurostimulation in patients with gastroparesis. [Journal Article]
- JSLS 2014 Jul; 18(3)
Patients with gastroparesis have significantly delayed gastric emptying because of impaired nerve function. Gastric neurostimulation from Enterra Therapy provides electrical pulses to the stomach tissue that promotes stimulation of stomach smooth muscle, thereby enhancing gastric emptying. This study evaluates the effectiveness of Enterra Therapy (Medtronic, Minneapolis, Minnesota) in reducing symptoms and improving the quality of life of patients with drug-refractory gastroparesis.In this study 25 patients underwent minimally invasive, laparoscopic placement of the Enterra Therapy device. Patients were asked to rank their severity of symptoms and quality of life retrospectively by completing the Gastrointestinal Symptoms Rating Scale and Short Form 36 Health Survey with respect to their condition before and 6 months after initiation of Enterra Therapy.Eighteen patients completed the surveys. Patients showed statistically significant improvement in their overall Gastrointestinal Symptoms Rating Scale scores and the mental health component of the Short Form 36 Health Survey.Currently, Enterra Therapy has Humanitarian Use Device status, which means that more clinical evidence is needed to prove its effectiveness in gastroparesis. By showing that Enterra Therapy reduces symptoms of gastroparesis and improves patient quality of life, this study contributes to the increasing amount of data supporting its use and potential Food and Drug Administration approval.
- Ventilator-associated respiratory infection following lung transplantation. [JOURNAL ARTICLE]
- Eur Respir J 2014 Oct 30.
The medical records of 170 adult patients who underwent lung transplantation between January 2010 and December 2012 were reviewed to assess the incidence, causative organisms, risk factors and outcomes of post-operative pneumonia and tracheobronchitis. 20 (12%) patients suffered 24 episodes of ventilator-associated pneumonia. The condition was associated with mean increases of 43 days in mechanical ventilation and of 35 days in hospital stay, and significantly higher hospital mortality (OR 9.0, 95% CI 3.2-25.1). Pseudomonas aeruginosa (eight out of 12 patients were multidrug-resistant) was the most common pathogen, followed by Enterobacteriaceae (one out of five patients produced extended-spectrum β-lactamases). Gastroparesis occurred in 55 (32%) patients and was significantly associated with pneumonia (OR 6.2, 95% CI 2.2-17.2). Ventilator-associated tracheobronchitis was associated with a mean increase of 28 days in mechanical ventilation and 30.5 days in hospital stay, but was not associated with higher mortality (OR 1.2, 95% CI 0.4-3.2). Pseudomonas aeruginosa (six out of 16 patients were multidrug resistant) was the most common pathogen, followed by Enterobacteriaceae (three out of 14 patients produced extended-spectrum β-lactamase). Patients with gastroparesis also had more episodes of ventilator-associated tracheobronchitis (40% versus 12%, p<0.001). In conclusion, ventilator-associated pneumonia following lung transplantation increased mortality. Preventing gastroparesis probably decreases the risk of pneumonia and tracheobronchitis. Multidrug-resistant bacteria frequently cause post-lung-transplantation pneumonia and tracheobronchitis.
- The investigational drug camicinal for the treatment of gastroparesis. [JOURNAL ARTICLE]
- Expert Opin Investig Drugs 2015 Jan; 24(1):133-140.
Introduction: Gastroparesis is a syndrome of delayed gastric emptying in the absence of mechanical obstruction that presents with upper gastrointestinal symptoms. Despite its growing prevalence, there remains an unmet clinical need for more efficacious prokinetic treatment options. The current market includes prokinetic agents that reduce gastroparesis symptoms. However, adverse drug effects and tachyphylaxis with repeated dosing are among the factors that limit their use. Camicinal (GSK962040) is the most advanced, small-molecule, selective motilin receptor agonist with therapeutic potential to date. Areas covered: This article reviews the literature on the limitations of current prokinetic agents used in the treatment of gastroparesis. It also summarizes the current evidence and influential clinical trial results involving the investigational drug camicinal, and shares its preliminary findings from the literature. Expert opinion: Camicinal represents a new opportunity as a treatment in a clinical area in need of new agents. There is emerging literature to support how the drug addresses both gastroparesis symptoms and dysmotility with no significant adverse effects or tachyphylaxis reported to date. Challenges remain in getting a new compound approved for gastroparesis. However, careful design of future trials will help to continue the record of success camicinal trials have had thus far.