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- Treatment of Functional Dyspepsia and Gastroparesis. [JOURNAL ARTICLE]
- Curr Treat Options Gastroenterol 2014 Aug 30.
Functional dyspepsia (FD) and gastroparesis (GP) are the two most prevalent gastric neuromuscular disorders. These disorders are frequently confused, have more similarities than differences, and can be thought of as two ends of a continuous spectrum of gastric neuromuscular disorders (Fig. 1). FD is currently defined by the Rome III criteria; it is now subdivided into a pain-predominant subtype (epigastric pain syndrome) and a meal-associated subtype (post-prandial distress syndrome). GP is defined by symptoms in conjunction with delayed gastric emptying in the absence of mechanical obstruction. Symptoms for both FD and GP are similar and include epigastric pain or discomfort, early satiety, bloating, and post-prandial nausea. Vomiting can occur with either diagnosis; it is typically more common in GP. A patient suspected of having either FD or GP should undergo upper endoscopy. In suspected FD, upper endoscopy is required to exclude an alternative organic cause for the patient's symptoms; however, most (70 %) patients with dyspeptic symptoms will have FD rather than an organic disorder. In suspected GP, upper endoscopy is required to rule out a mechanical obstruction. A 4-hour solid-phase gastric emptying scan is recommended to confirm the diagnosis of GP; its utility is unclear in patients with FD, as it may not change treatment. Once the diagnosis of FD or GP is made, treatment should focus on the predominant symptom. This is especially true in patients with GP, as accelerating gastric emptying with the use of prokinetics may not necessarily translate into an improvement in symptoms. Unfortunately, no medication is currently approved for the treatment of FD and, thus, technically, all treatment options remain off-label, including medications for visceral pain (e.g., tricyclic antidepressants) and nausea. This review focuses on treatment options for FD and GP with an emphasis on new advances in the field over the last several years.
- Macrophages in diabetic gastroparesis - the missing link? [JOURNAL ARTICLE]
- Neurogastroenterol Motil 2014 Aug 28.
Diabetic gastroparesis results in significant morbidity for patients and major economic burden for society. Treatment options for diabetic gastroparesis are currently directed at symptom control rather than the underlying disease and are limited. The pathophysiology of diabetic gastroparesis includes damage to intrinsic and extrinsic neurons, smooth muscle, and interstitial cells of Cajal (ICC). Oxidative damage in diabetes appears to be one of the primary insults involved in the pathogenesis of several complications of diabetes, including gastroparesis. Recent studies have highlighted the potential role of macrophages as key cellular elements in the pathogenesis of diabetic gastroparesis. Macrophages are important for both homeostasis and defense against a variety of pathogens. Heme oxygenase 1 (HO1), an enzyme expressed in a subset of macrophages has emerged as a major protective mechanism against oxidative stress. Activation of macrophages with high levels of HO1 expression protects against development of delayed gastric emptying in animal models of diabetes, while activation of macrophages that do not express HO1 are linked to neuromuscular cell injury. Targeting macrophages and HO1 may therefore be a therapeutic option in diabetic gastroparesis.This report briefly reviews the pathophysiology of diabetic gastroparesis with a focus on oxidative damage and how activation and polarization of different subtypes of macrophages in the muscularis propria determines development of delay in gastric emptying or protects against its development.
- Medications associated with restless legs syndrome: a case-control study in the US Renal Data System (USRDS). [JOURNAL ARTICLE]
- Sleep Med 2014 Jun 13.
The objective of this study was to determine the association between the usage of four classes of "at-risk" medications (antidepressants, neuroleptics, antihistamines, and antiemetics with dopamine blockade) and restless legs syndrome (RLS) in dialysis patients within the United States Renal Data System (USRDS).This was a case-control design within a national (United States) patient registry of all patients with end-stage renal disease (ESRD) in the USRDS anytime during the period of 1 October 2006 to 31 December 2010, inclusive. A total of 16,165 ESRD patients (3234 cases; 12,931 age-, sex-, and race-matched controls) were studied.All four classes of "at-risk" medications see widespread use among patients in the USRDS. All were associated with increased odds of an RLS diagnosis (range of odds ratios, 1.47-2.28; all p < 0.0001) during the period of observation. Results were unchanged when controlling for time on hemodialysis. Usage of more than one class of medication increased the odds for having RLS.ESRD patients often receive medication intended for relief of conditions associated with their disease, such as depression and psychological issues, pruritus, and gastroparesis; however, such medications may increase the risk of RLS. Given the high prevalence of RLS in ESRD patients, these medications should only be used when their benefits clearly outweigh the risk of development of the troubling and distressing symptoms of RLS.
- The effectiveness of acupuncture in postoperative gastroparesis syndrome - A systematic review and meta-analysis. [REVIEW]
- Complement Ther Med 2014 Aug; 22(4):767-786.
Postoperative gastroparesis syndrome (PGS) which is mainly manifested as delayed gastric emptying is often caused by upper abdominal and sometimes lower abdominal surgery. In view of the side effects of drugs therapy, the search of supplementary and alternative has been of increasing interest.This paper included a systematic review and meta-analysis on the use of acupuncture and acupoints selection in PGS. Quality for meta-analysis was evaluated using GRADE while each trial was assessed with CONSORT and STRICTA for TCM.Randomized controlled trials (RCTs) comparing acupuncture with non-acupuncture treatment were identified from databases PubMed, EBSCO, Ovid, Cochrane, CNKI and Wanfangdata. Meta-analysis on eligible studies was performed using fixed-effects model with RevMan 5.2. Results were expressed as relative risk (RR) for dichotomous data, and 95% confidence interval (CI) were calculated.Of the 348 studies reviewed, 16 RCTs met the inclusion criteria for review while 7 RCTs, 188 patients (intervention) and 182 patients (control) met the criteria for meta-analysis. Both acupuncture and acupuncture combined with medication showed significant higher total effective rate than control (usual care/medication); with (RR 1.27, 95% CI 1.13, 1.44; P<0.0001) and (RR 1.37, 95% CI 1.18, 1.58; P<0.0001) respectively. All included RCTs reported positive effect of acupuncture in PGS treatment. ST36, CV12 and PC6 seemed to be the common acupoints selected.The results suggested acupuncture might be effective to improve PGS, however, a definite conclusion could not be drawn due to low quality of trials. Further large-scale, high-quality randomized clinical trials are needed to validate this.PROSPERO CRD42013005485.
- Rapid or normal gastric emptying as new supportive criteria for diagnosing cyclic vomiting syndrome in adults. [Journal Article]
- Med Sci Monit 2014.:1491-5.
Background Cyclic vomiting syndrome (CVS) in adults is a disorder characterized by recurrent and stereotypic episodes of severe nausea, vomiting and abdominal pain separated by symptom-free intervals. Our goal was to investigate gastric emptying (GE) in CVS patients. Material and Methods This was a retrospective study of 30 adult patients who met Rome III diagnostic criteria for CVS. Rapid GE was defined using two different predefined criteria as either <50% isotope retention or <65% isotope retention at 1st hour and/or <20% at 2nd hour. Results Of the 30 patients (25 had 4-hr GE) diagnosed with CVS, 22 were females and 8 males with a mean age of 39 years. Overall, 20 (80%) of the 25 CVS patients met the predefined criteria of <50% retention for rapid GE in the first hour. Fifteen (60%) met the 2-hour criteria for rapid emptying of <20% retention. Five (16.6%) patients of the 25 had a normal GE with a mean retention at the first hour of 65% (52-78%). Nine (36%) also met another predefined criteria of <35% retention for rapid GE in the first hour. Sixteen (64%) met criteria for normal GE. Conclusions (1) In adult CVS patients, GE is either rapid or normal, clearly distinguishing this entity from gastroparesis. (2) Cyclic vomiting syndrome is an important new etiology to explain the finding of rapid GE on a radionuclide test. (3) We suggest that rapid gastric emptying should be added as supportive criteria for diagnosing CVS in adults.
- A Gluten-Free Vegan Meal for Gastric Emptying Scintigraphy: Establishment of Reference Values and Its Utilization in the Evaluation of Diabetic Gastroparesis. [JOURNAL ARTICLE]
- Clin Nucl Med 2014 Aug 19.
The aim of this study was to describe the preparation of radiolabeled idli (savory cake) meal for use as an alternate to the egg white sandwich (EWS) meal in gastric emptying scintigraphy (GES). Furthermore, the aim of this study was to establish normal emptying rates for this meal and present our experience in using it in the evaluation of diabetic gastroparesis.The meal was prepared using a universally available packaged mix labeled with 1 mCi Tc sulfur colloid, and the stability of labeling was tested up to 4 hours in simulated gastric fluid. One hundred thirteen healthy volunteers (aged 20-78 years; 54 women, 59 men) underwent GES study using the idli meal. Gastric retention at one-half, 1, 2, and 4 hours after ingestion of the meal was estimated, and the normal limits were set using the fifth and 95th percentile values at each period. Having established its normal emptying rates, the idli meal was further used to evaluate 70 patients suspected with diabetic gastroparesis.The idli meal, with a calorific value ≈282 kcal, has a relatively higher fat content (8% of total mass) than EWS. More than 96% of Tc sulfur colloid remained bound to the meal after 4 hours suspension in simulated gastric fluid. Gastric retention greater than 30% and greater than 6% at 2 hours and 4 hours, respectively, indicated delayed gastric emptying, whereas retention less than 30% at 1 hour suggested rapid emptying. Among patients suspected with diabetic gastroparesis, delayed gastric emptying was identified in 76%, and rapid emptying was seen in 4.2%.Radiolabeled idli meal is a good alternative to EWS meal for routine GES, especially among patients with specific dietary restrictions.
- Rectal sensitivity in diabetes patients with symptoms of gastroparesis. [Journal Article]
- J Diabetes Res 2014.:784841.
In a clinical setting, diabetic autonomic complications (cardiac, gastrointestinal, urogenital, etc.) are often handled as separate entities. We investigated rectal sensitivity to heat, mechanical distension, and electrical stimulations in 20 patients with diabetes and symptoms of gastroparesis, to evaluate the extent of visceral neuronal damage. Furthermore, to evaluate the relation between the nervous structures we examined gastric emptying and cardiac autonomic function with the hypothesis being an association between these. We found that 60% of patients had delayed gastric empting. Rectal hyposensitivity was a general finding as they tolerated 67% higher thermal, 42% more mechanical, and 33% higher electrical current intensity compared to healthy controls. In patients, most heart rate variability parameters were reduced; they reported significantly more gastrointestinal symptoms and a reduced quality of life in all SF-36 domains. Shortened RR interval correlated with reduced rectal temperature sensitivity, and gastric retention rate was negatively associated with symptoms of nausea and vomiting. To conclude, in these patients with signs and symptoms of diabetic gastroparesis, rectal sensitivity was reduced, and heart rate variability was impaired. Thus, we suggest regarding diabetic autonomic neuropathy as a diffuse disorder. Symptoms of widespread autonomic dysfunction and sensory disorders should be expected and treated in these patients.
- Pre-operative opioid analgesia reduces clinical success of laparoscopic gastric electrical stimulation placement in patients with gastroparesis. [JOURNAL ARTICLE]
- Surg Endosc 2014 Aug 13.
Gastroparesis is a common chronic and costly disorder for which medical therapy is often unsuccessful. Gastric electrical stimulation (GES) has been used to treat refractory cases, however, response is variable and difficult to predict. This study aims to assess whether pre-operative opioid analgesics (OA) use affects clinical success of GES.Records of 128 patients who underwent laparoscopic GES placement from March 2001 to September 2012 were analyzed retrospectively. Data collected included demographics, surgical outcomes, and clinical parameters. Pre- and post-operative opioid analgesic dosing (No = 0 morphine equivalents (ME)/day, Low = 0-40 ME/day, Mid = 41-80 ME/day, High >80 ME/day), as well as clinical symptom assessment was collected for up to 3 years post-operatively. Clinical success was defined as (1) OA reduction of >50 %, (2) maintenance of weight, or (3) symptom improvement. Descriptive statistics were computed for all factors. A p < 0.05 was considered statistically significant.Fifty-three patients were on OA pre-operatively compared to 69 patients who were not. Patients not on OA pre-operatively were less likely than those on OA pre-op group to be on OA post-operatively (p = 0.005); however, there were no differences in weight or symptom improvement. Sub-group analysis of the 53 patients on OA demonstrated significant improvement in clinical symptoms in the low-morphine cohort compared to the mid-morphine cohort (p = 0.02), and OA dosing post-operatively in the low-morphine cohort diminished significantly compared to mid- and high-morphine cohort (p = 0.032). There was no significant difference in weight.OA dosing pre-operatively significantly affects clinical success of GES placement. Criteria for offering GES implantation may need to take OA dosing into consideration.
- Recent progress in gastric dysrhythmia: pathophysiology, clinical significance and future horizons. [JOURNAL ARTICLE]
- Clin Exp Pharmacol Physiol 2014 Aug 12.
Gastric dysrhythmia continues to be of uncertain diagnostic and therapeutic significance. However, recent progress has been substantial, with technical advances, theoretical insights and experimental discoveries offering new translational opportunities. The discoveries that interstitial cells of Cajal (ICC) generate slow waves and that ICC defects are associated with dysmotility have reinvigorated gastric dysrhythmia research. Increasing evidence now suggests that ICC depletion and damage, network disruption and channelopathies may lead to aberrant slow wave initiation and conduction. Histological and high-resolution (HR) electrical mapping studies have now redefined the human 'gastric conduction system', providing an improved baseline for dysrhythmia research. The application of HR mapping to dysrhythmia has also generated important new insights into the spatiotemporal dynamics of dysrhythmia onset and maintenance, resulting in the emergence of new provisional classification schemes. Meanwhile, the strong associations between gastric functional disorders and electrogastrography (EGG) abnormalities (e.g. in gastroparesis, unexplained nausea and vomiting, and functional dyspepsia) continue to motivate deeper inquiries into the nature and causes of GI dysrhythmias. In future, technical progress in EGG methods, new HR mapping devices and software, wireless slow wave acquisition systems, and improved gastric pacing devices may achieve validated applications in clinical practice. Neurohormonal factors in dysrhythmogenesis also continue to be elucidated, and a deepening understanding of these mechanisms may open opportunities for drug design for treating dysrhythmias. However, for all translational goals, it still remains to be seen whether dysrhythmia can be corrected in a way that meaningfully improves organ function and symptoms in patients. This article is protected by copyright. All rights reserved.
- Major complications of cryoballoon catheter ablation for atrial fibrillation and their management. [JOURNAL ARTICLE]
- Expert Rev Cardiovasc Ther 2014 Aug 12.:1-8.
Atrial fibrillation (AF) is the most common symptomatic and sustained cardiac arrhythmia. It affects approximately 2-3 million people in the USA alone with an increased incidence and prevalence worldwide. It is associated, in addition to worsening quality of life, with increased morbidity and mortality especially in poorly controlled AF, affecting mostly those older than 65 years of age. Radiofrequency ablation was found to be a good strategy for focal isolation of pulmonary veins triggering from the vulnerable atrial substrate but is a time-consuming procedure and carries the risk of multiple complications like tamponade which could be fatal, atrioesophageal fistula and local thrombus formation at the site of ablation. Cryoballoon ablation with pulmonary vein isolation has emerged in the past few years as a breakthrough novel technology for the treatment of drug-refractory AF. It is a relatively simple alternative for point-by-point radiofrequency ablation of paroxysmal AF and is associated with fewer incidences of fatal complications such as cardiac perforation. As experience with this new tool accumulates, the field faces new challenges in the form of rare compilations including gastroparesis, phrenic nerve palsy, atrioesophageal fistula, pulmonary vein stenosis, thromboembolism pericardial effusion, and tamponade.