Mean nocturnal baseline impedance in gastro-esophageal reflux disease diagnosis:Should we strictly follow the Lyon 2 Consensus?

Clinical practice guidelines drive clinical practice and clinicians rely to them when trying to answer their most common questions.One of the most important position papers in the field of gastro-esophageal reflux disease(GERD)is the one produced by the Lyon Consensus.Recently an updated second version has been released.Mean nocturnal baseline impedance(MNBI)was proposed by the first Consensus to act as supportive evidence for GERD diagnosis.Originally a cut-off of 2292 Ohms was proposed,a value revised in the second edition.The updated Consensus recommended that an MNBI<1500 Ohms strongly suggests GERD while a value>2500 Ohms can be used to refute GERD.The proposed cut-offs move in the correct direction by diminishing the original cut-off,nevertheless they arise from a study of normal subjects where cut-offs were provided by measuring the mean value±2SD and not in symptomatic patients.However,data exist that even symptomatic patients with inconclusive disease or reflux hypersensitivity(RH)show lower MNBI values in comparison to normal subjects or patients with functional heartburn(FH).Moreover,according to the data,MNBI,even among symptomatic patients,is affected by age and body mass index.Also,various studies have proposed different cut-offs by using receiver operating characteristic curve analysis even lower than the one proposed.Finally,no information is given for patients submitted to on-proton pump inhibitors pH-impedance studies even if new and extremely important data now exist.Therefore,even if MNBI is an extremely important tool when trying to approach patients with reflux symptoms and could distinguish conclusive GERD from RH or FH,its values should be interpreted with caution.

Management of gastro-esophageal reflux disease:Practice-oriented answers to clinical questions

Gastro-esophageal reflux disease(GERD)is a condition which is frequently faced by primary care physicians and gastroenterologists.Improving management of GERD is crucial to maximise both patient care and resource utilization.In fact,the management of patients with GERD is complex and poses several questions to the clinician who faces them in clinical practice.For instance,many aspects should be considered,including the appropriateness of indication to endoscopy,the quality of the endoscopic examination,the use and interpretation of ambulatory reflux testing,and the choice and management of anti-reflux treatments,i.e.,protonpump inhibitors and surgery.Aim of the present review was to provide a comprehensive update on the clinical management of patients with GERD,through a literature review on the diagnosis and management of patients with GER symptoms.In details,we provide practice-oriented concise answers to clinical questions,with the aim of optimising patient management and healthcare resource use.

Overlapping approach Proton Pump Inhibitors/Nux vomica-Heel as new intervention for gastro-esophageal reflux management:Delphi consensus study

BACKGROUND Gastro-esophageal reflux disease(GERD)may affect the upper digestive tract;up to 20%of population in Western nations are affected by GERD.Antacids,histamine H2-receptor antagonists,and Proton Pump Inhibitors(PPIs)are considered the referring medications for GERD.Nevertheless,PPIs must be managed carefully because their use,especially chronic,could be linked with some adverse effects.An effective and safe alternative pharmacological tool for GERD is needed.After the identification of potentially new medications to flank PPIs,it is mandatory to revise and improve good clinical practices even through a consensus process.AIM To optimize diagnosis and treatment guidelines for GERD through a consensus based on Delphi method.METHODS The availability of clinical studies describing the action of the multicomponent/multitarget medication Nux vomica-Heel,subject of the consensus,is the basic prerequisite for the consensus itself.A modified Delphi process was used to reach a consensus among a panel of Italian GERD specialists on the overlapping approach PPIs/Nux vomica-Heel as a new intervention model for the management of GERD.The Voting Consensus group was composed of 49 Italian Medical Doctors with different specializations:Gastroenterology,otolaryngology,geriatrics,and general medicine.A scientific committee analyzed the literature,determined areas that required investigation(in agreement with the multiple-choice questionnaire results),and identified two topics of interest:(1)GERD disease;and(2)GERD treatment.Statements for each of these topics were then formulated and validated.The Delphi process involved two rounds of questioning submitted to the panel experts using an online platform.RESULTS According to their routinary GERD practice and current clinical evidence,the panel members provided feedback to each questionnaire statement.The experts evaluated 15 statements and reached consensus on all 15.The statements regarding the GERD disease showed high levels of agreement,with consensus ranging from 70%to 92%.The statements regarding the GERD treatment also showed very high levels of agreement,with consensus ranging from 90%to 100%.This Delphi process was able to reach consensus among physicians in relevant aspects of GERD management,such as the adoption of a new approach to treat patients with GERD based on the overlapping between PPIs and Nux vomica-Heel.The consensus was unanimous among the physicians with different specializations,underlying the uniqueness of the agreement reached to identify in the overlapping approach between PPIs and Nux vomica-Heel a new intervention model for GERD management.The results support that an effective approach to deprescribe PPIs through a progressive decalage timetable(reducing PPIs administration to as-needed use),should be considered.CONCLUSION Nux vomica-Heel appears to be a valid opportunity for GERD treatment to favor the deprescription of PPIs and to maintain low disease activity together with the symptomatology remission.

Navigating reflux disease after achalasia treatments:Balancing risks and benefits

The peroral endoscopic myotomy(POEM)procedure has revolutionized the management of achalasia in many centres around the world as it offers patients a minimally invasive endoscopic solution to their dysphagia caused by achalasia.Alongside its success in alleviating dysphagia,concerns regarding postoperative gastroesophageal reflux disease have emerged as a pertinent issue which are not fully resolved.In this study,Nabi et al have comprehensively reviewed the topic of the prediction,prevention and management of gastroesophageal reflux after POEM.POEM is a purely endoscopic procedure which is usually performed without any anti-reflux procedure.Certain patients may be better served by a laparoscopic Heller’s myotomy and fundoplication and it is important that gastroenterologists and surgeons provide comprehensive risks and benefits of each achalasia treatment option so that patients can decide what treatment is best for them.This article by Nabi et al provides a comprehensive review of the current status of this issue to allow these discussions to occur.

Investigating causal links between gastroesophageal reflux disease and essential hypertension

Gastroesophageal reflux disease(GERD)is a prevalent global health concern with a rising incidence.Various risk factors,including obesity,hiatal hernia,and smo-king,contribute to its development.Recent research suggests associations bet-ween GERD and metabolic syndrome,cardiac diseases,and hypertension(HTN).Mechanisms linking GERD to HTN involve autonomic dysfunction,inflammatory states,and endothelial dysfunction.Furthermore,GERD medications such as pro-ton-pump inhibitors may impact blood pressure regulation.Conversely,antihy-pertensive medications like beta-blockers and calcium channel blockers can exacerbate GERD symptoms.While bidirectional causality exists between GERD and HTN,longitudinal studies are warranted to elucidate the precise relationship.Treatment of GERD,including anti-reflux surgery,may positively influence HTN control.However,the interplay of lifestyle factors,comorbidities,and medications necessitates further investigation to comprehensively understand this relation-ship.In this editorial,we comment on the article published by Wei et al in the recent issue of the World Journal of Clinical Cases.We evaluate their claims on the causal association between GERD and HTN.

Proton pump inhibitor resistance, the real challenge in gastro-esophageal reflux disease

Gastro-esophageal reflux disease(GERD)is one of the most prevalent chronic diseases.Although proton pump inhibitors(PPIs)represent the mainstay of treatment both for healing erosive esophagitis and for symptom relief,several studies have shown that up to 40%of GERD patients reported either partial or complete lack of response of their symptoms to a standard PPI dose once daily.Several mechanisms have been proposed as involved in PPIs resistance,including ineffective control of gastric acid secretion,esophageal hypersensitivity,ultrastructural and functional changes in the esophageal epithelium.The diagnostic evaluation of a refractory GERD patients should include an accurate clinical evaluation,upper endoscopy,esophageal manometry and ambulatory pH-impedance monitoring,which allows to discriminate non-erosive reflux disease patients from those presenting esophageal hypersensitivity or functional heartburn.Treatment has been primarily based on doubling the PPI dose or switching to another PPI.Patients with proven disease,not responding to PPI twice daily,are eligible for anti-reflux surgery.

Comparative clinical trial of S-pantoprazole versus racemic pantoprazole in the treatment of gastro-esophageal reflux disease

AIM: To compare the effi cacy and tolerability of S-pan- toprazole (20 mg once a day) versus racemic Panto- prazole (40 mg once a day) in the treatment of gastro- esophageal reflux disease (GERD). METHODS: This multi-centre, randomized, double-blind clinical trial consisted of 369 patients of either sex suf- fering from GERD. Patients were randomly assigned to receive either one tablet (20 mg) of S-pantoprazole once a day (test group) or 40 mg racemic pantoprazole once a day (reference group) for 28 d. Patients were evaluated for reduction in baseline on d 0, GERD symptom score on d 14 and 28, occurrence of any adverse effect during the course of therapy. Gastrointestinal (GI) endoscopy was performed in 54 patients enrolled at one of the study centers at baseline and on d 28. RESULTS: Signifi cant reduction in the scores (mean and median) for heart burn (P < 0.0001), acid regurgitation (P < 0.0001), bloating (P < 0.0001), nausea (P < 0.0001) and dysphagia (P < 0.001) was achieved in both groups on d 14 with further reduction on continuing the therapy till 28 d. There was a statistically signifi cant difference in the proportion of patients showing improvement in acid regurgitation and bloating on d 14 and 28 (P = 0.004 for acid regurgitation; P = 0.03 for bloating) and heart burn on d 28 (P = 0.01) between the two groups, with a higher proportion in the test group than in the refer- ence group. Absolute risk reductions for heartburn/acid regurgitation/bloating were approximately 15% on d 14 and 10% on d 28. The relative risk reductions were 26%-33% on d 14 and 15% on d 28. GI endoscopy showed no signifi cant difference in healing of esophagitis (P = 1) and gastric erosions (P = 0.27) between the two groups. None of the patients in either group reported any adverse effect during the course of therapy.CONCLUSION: In GERD, S-pantoprazole (20 mg) is more effective than racemic pantoprazole (40 mg) in improving symptoms of heartburn, acid regurgitation, bloating and equally effective in healing esophagitis and gastric erosions. The relative risk reduction is 15%-33%. Both drugs are safe and well tolerated.

Outcome of nonerosive gastro-esophageal reflux disease patients with pathological acid exposure

AIM： To assess the management and outcome of nonerosive gastro-esophageal reflux disease （NERD） patients who were identified retrospectively, after a 5-year follow-up. METHODS： We included patients with gastro-esophageal reflux disease （GERD） symptoms who had a negative endoscopy result and pathological 24-h esophageal pH-monitoring while off therapy. We interviewed them after an average period of 5 years （range 3.5-7 years） by means of a structured questionnaire to assess presence of GERD symptoms, related therapy, updated endoscopic data and other features. We assessed predictors of esophagitis development by means of univariate and multivariate statistical analysis. RESULTS： 260 patients （137 women） were included. Predominant GERD symptoms were heartburn and regurgitation in 103/260 （40%）. 70% received a maintenance treatment, which was proton pump inhibitor （PPI） in 55% of cases. An average number of 1.5 symptomatic relapses per patient/year of follow-up were observed. A progression to erosive gastro-esophageal reflux disease （ERD） was found in 58/193 （30.0%） of patients undergoing repeat endoscopy; 72% of these were Los Angeles grade A-B. CONCLUSION： This study to ERD occurs in about 5% shows that progression of NERD cases per year, despite therapy. Only two factors consistently and independently influence progression： smoking and absence of PPI therapy.

Gender difference in gastro-esophageal reflux diseases

The incidence of esophageal adenocarcinoma(EAC) has risen sharply in western countries over the past 4 decades. This type of cancer is considered to follow a transitional process that goes from gastro-esophageal reflux disease(GERD) to Barrett's esophagus(BE,a metaplastic condition of the distal esophagus), a precursor lesion and ultimately adenocarcinoma. This spectrum of GERD is strongly predominant in males due to an unidentified mechanism. Several epidemiologic studies have des cribed that the prevalence of GERD, BE and EAC in women is closely related to reproductive status, which suggests a possible association with the estrogen level. Recently, we revealed in an in vivo study that the inactivation of mast cells by the anti-inflammatory function of estrogen may account for the gender difference in the GERD spectrum. Other studies have described the contribution of female steroid hormones to the gender difference in these diseases. Estrogen is reported to modulate the metabolism of fat, and obesity is a main risk factor of GERDs. Moreover, estrogen could confer esophageal epithelial resistance to causative refluxate. These functions of estrogen might explain the approximately 20-year delay in the incidence of BE and the subsequent development of EAC in women compared to men, and this effect may be responsible for the male predominance. However, some observational studies demonstrated that hormone replacement therapy exerts controversial effects in GERD patients. Nevertheless, the estrogen-related endocrine milieu may prevent disease progression toward carcinogenesis in GERD patients. The development of innovative alternatives to conventional acid suppressors may become possible by clarifying the mechanisms of estrogen.

Gastro-esophageal reflux disease and obesity, where is the link?

The confluence between the increased prevalence of gastro-esophageal reflux disease(GERD)and of obesity has generated great interest in the association between these two conditions.Several studies have addressed the potential relationship between GERD and obesity,but the exact mechanism by which obesity causes reflux disease still remains to be clearly defined.A commonly suggested pathogenetic pathway is the increased abdominal pressure which relaxes the lower esophageal sphincter,thus exposing the esophageal mucosal to gastric content.Apart from the mechanical pressure,visceral fat is metabolically active and it has been strongly associated with serum levels of adipocytokines including interleukin-6 and tumor necrosis factorα,which may play a role in GERD or consequent carcinogenesis.This summary is aimed to explore the potential mechanisms responsible for the association between GERD and obesity,and to better understand the possible role of weight loss as a therapeutic approach for GERD.

Transoral incisionless fundoplication for gastro-esophageal reflux disease: Techniques and outcomes

Gastro-esophageal reflux disease(GERD)is a verycommon disorder that results primarily from the loss of an effective antireflux barrier,which forms a mechanical obstacle to the retrograde movement of gastric content.GERD can be currently treated by medical therapy,surgical or endoscopic transoral intervention.Medical therapy is the most common approach,though concerns have been increasingly raised in recent years about the potential side effects of continuous longterm medication,drug intolerance or unresponsiveness,and the need for high dosages for long periods to treat symptoms or prevent recurrences.Surgery too may in some cases have consequences such as longlasting dysphagia,flatulence,inability to belch or vomit,diarrhea,or functional dyspepsia related to delayed gastric emptying.In the last few years,transoral incisionless fundoplication(TIF)has proved an effective and promising therapeutic option as an alternative to medical and surgical therapy.This review describes the steps of the TIF technique,using the Esophy X&#174;device and the MUSETM system.Complications and their management are described in detail,and the recent literature regarding the outcomes is reviewed.TIF reconfigures the tissue to obtain a full-thickness gastroesophageal valve from inside the stomach,by serosato-serosa plications which include the muscle layers.To date the procedure has achieved lasting improvement of GERD symptoms(up to six years),cessation or reduction of proton pump inhibitor medication in about 75%of patients,and improvement of functional findings,measured by either p H or impedance monitoring.

Clinical usefulness of adherence to gastro-esophageal reflux disease guideline by Spanish gastroenterologists

AIM:To investigate usefulness of adherence to gastroesophageal reflux disease(GERD) guideline established by the Spanish Association of Gastroenterology.METHODS:Prospective,observational and multicentre study of 301 patients with typical symptoms of GERD who should be managed in accordance with guidelines and were attended by gastroenterologists in daily practice.Patients(aged > 18 years) were eligible for inclusion if they had typical symptoms of GERD(heartburn and/or acid regurgitation) as the major complaint in the presence or absence of accompanying atypical symptoms,such as dyspeptic symptoms and/or supraesophageal symptoms.Diagnostic and therapeutic decisions should be made based on specific recommendations of the Spanish clinical practice guideline for GERD which is a widely disseminated and well known instrument among Spanish in digestive disease specialists.RESULTS:Endoscopy was indicated in 123(41%) patients:50 with alarm symptoms,32 with age > 50 years without alarm symptom.Seventy-two patients(58.5%) had esophagitis(grade A,23,grade B,28,grade C,18,grade D,3).In the presence of alarm symptoms,endoscopy was indicated consistently with recommendations in 98% of cases.However,in the absence of alarm symptoms,endoscopy was indicated in 33% of patients > 50 years(not recommended by the guideline).Adherence for proton pump inhibitors(PPIs) therapy was 80%,but doses prescribed were lower(half) in 5% of cases and higher(double) in 15%.Adherence regarding duration of PPI therapy was 69%;duration was shorter than recommended in 1%(4 wk in esophagitis grades C-D) or longer in 30%(8 wk in esophagitis grades A-B or in patients without endoscopy).Treatment response was higher when PPI doses were consistent with guidelines,although differences were not significant(95% vs 85%).CONCLUSION:GERD guideline compliance was quite good although endoscopy was over indicated in patients > 50 years without alarm symptoms;PPIs were prescribed at higher doses and longer duration.

Anesthetic management of the SRS^(TM) endoscopic stapling system for gastro-esophageal reflux disease

The SRS TM Endoscopic Stapling System(Medigus,Tel Aviv,Israel) is a new tool capable of creating a totally endoscopic fundoplication,combined with an endoscope,endoscopic ultrasound and a surgical stapler.SRS TM endoscopic stapling for gastro-esophageal reflux disease is a minimally invasive,outpatient procedure,which requires general anesthesia with positive-pressure ventilation.Keeping the patient on positive endexpiratory pressure(PEEP) may minimize the pressure gradient between the esophagus and the mediastinum,as well as help to prevent air from leaking around the screws and causing pneumomediastinum.In addition,in patients with hiatal hernia,higher PEEP levels may be required to increase intra-thoracic pressure and to force the stomach to slide into the abdomen for ease of endoscopy.We advise smoother emergence from anesthesia,taking precautions for retching,postoperative nausea and vomiting(PONV),while coughing and gagging during extubation and PONV may affect the success of the procedure.Total intravenous anesthesia with propofol and remifentanil seems to be a good choice for these reasons.

Test-based exclusion diets in gastro-esophageal reflux disease patients:A randomized controlled pilot trial

AIM: To investigate the clinical response of gastro-esophageal reflux disease (GERD) symptoms to exclusion diets based on food intolerance tests.

Symptoms of Gastro-Esophageal Reflux Disease: A Comparative Study between Elderly and Younger Patients in Japan

The difference in gastro-esophageal reflux disease (GERD) symptoms between elderly and younger GERD patients has not been fully studied. Our aim was to examine if there was any difference in the degree of GERD symptoms between elderly and younger patients with reflux esophagitis. Patients who were diagnosed by endoscopic examination as having reflux esophagitis and who answered the questionnaire on the frequency scale for the symptoms of GERD (FSSG) were included. Elderly and younger adult patients were defined as patients aged 65 and over or less than 65, respectively. 596 subjects were included. 184 subjects (mean 71.1 years;114 males) were classified into the Elderly group, and 412 subjects (mean 51.2 years;307 males) into the Younger group. The mean FSSG score of the Elderly and Younger groups was 6.7 and 8.4, respectively (p = 0.0024). Among those with severe esophagitis, the mean FSSG score of the Elderly and Younger groups was 8.5 and 8.7, respectively (p = 0.58). Although elderly patients tended to have less degree of GERD symptoms than younger patients, these findings suggest that there may be no significant age-related difference in complaints of GERD symptoms among severe reflux esophagitis patients.

Increased prevalence of symptoms of gastroesophageal reflux diseases in type 2 diabetics with neuropathy

AIM： To analyze the prevalence of gastroesophageal reflux disease （GERD） related symptoms in patients with diabetes mellitus （DM） and to find out the relationship between diabetic neuropathy and the prevalence of GERD symptoms. METHODS： In this prospective questionnaire study, 150 consecutive type 2 diabetic patients attending the endocrine clinic were enrolled. A junior physician helped the patients to understand the questions. Patients were asked about the presence of five most frequent symptoms of GERD that included heartburn （at least 1/wk）, regurgitation, chest pain, hoarseness of voice and chronic cough. Patients with past medical history of angina, COPD, asthma, cough due to ACEI or preexisting GERD prior to onset of diabetes and apparent psychiatric disorders were excluded from the survey. We further divided the patients into two groups based on presence or absence of peripheral neuropathy. Out of 150 patients, 46 had neuropathy, whereas 104 patients did not have neuropathy. Data are expressed as mean ± SD, and number of patients in each category and percentage of total patients in that group. Normal distributions between groups were compared with Student t test and the prevalence rates between groups were compared with Chi-square tests for significance. RESULTS： The average duration of diabetes were 12 ± 9.2 years and the average HbAlc level of this group was 7.7% ± 2.0%. The mean weight and BMI were 198 ± 54 Ibs. and 32 ± 7.2 kg/m^2. Forty percent （61/150） patients reported having at least one of the symptoms of GERD and thirty percent （45/150） reported having heartburn at least once a week. The prevalence of GERD symptoms is higher in patients with neuropathy than patients without neuropathy （58.7% vs 32.7%, P 〈 0.01）. The prevalence of heartburn, chest pain and chronic cough are also higher in patients with neuropathy than in patients without neuropathy （43.5% vs 24%; 10.9% vs 4.8% and 17.8% vs 6.7% respectively, P 〈 0.05）. CONCLUSION： The prevalence of GERD symptoms in type 2 DM is higher than in the general population. Our data suggest that DM neuropathy may be an important associated factor for developing GERD symptoms.

Cardiac autonomic dysfunction in patients with gastroesophageal reflux disease

AIM: To investigate autonomic nervous function in patients with a diagnosis of gastroesophageal reflux disease(GERD).METHODS: The investigation was performed on 29patients(14 men), aged 18-80 years(51.14 ± 18.34),who were referred to our Neurocardiology Laboratory at the Clinical and Hospital Center "Bezanijska Kosa"with a diagnosis of GERD. One hundred sixteen healthy volunteers matched in age and sex with the examinees served as the control group. The study protocol included the evaluation of autonomic function and hemodynamic status, short-term heart rate variability(HRV) analysis, 24 h ambulatory ECG monitoring with long-term HRV analysis and 24 h ambulatory blood pressure monitoring.RESULTS: Pathologic results of cardiovascular reflex test were more common among patients with reflux compared to the control group. Severe autonomic dysfunction was detected in 44.4% of patients and in7.9% of controls(P < 0.001). Parameters of short-term analysis of RR variability, which are the indicators ofvagal activity, had lower values in patients with GERD than in the control group. Long-term HRV analysis of time-domain parameters indicated lower values in patients with reflux disease when compared to the control group. Power spectral analysis of long-term HRV revealed lower low- and high-frequency values.Detailed 24 h ambulatory blood pressure analysis showed significantly higher values of systolic blood pressure and pulse pressure in the reflux group than in the control group.CONCLUSION: Patients with GERD have distortion of sympathetic and parasympathetic components of the autonomic nervous system, but impaired parasympathetic function appears more congruent to GERD.

Overlapping gastroesophageal reflux disease and irritable bowel syndrome:Increased dysfunctional symptoms

AIM:To investigate the association of gastroesophageal reflux disease (GERD) and irritable bowel syndrome (IBS) in Iranian patients and examine the prevalence of functional symptoms of the gastrointestinal tract in patients presenting with either IBS, GERD or both.METHODS: Six thousand four hundred and seventy six patients presented to the Gastro-intestinal (GI) clinic with symptoms of functional dysfunction of GI tract, 1419 patients (62.0% women, 38.0% men; mean age: 37.4±11.5 years) met Rome or Rome criteria(depending on the year of diagnosis)for IBS.2658 patients were diagnosed with GERD based on clinical presentation and endoscopic findings.We assessed other functional symptoms(epigastric pain,nausea,vomiting,belching,constipation and diarrhea)in patients suffering from GERD,IBS or both.RESULTS: Among IBS subjects, 63.6% (69.0% women, 31.0% men; mean age: 36.4±10.3 years) also hadGERD, whereas 34.7% of the non-IBS patients had GERD [odds ratio (OR) =3.2, 95% confidence interval (CI): 2.9-3.7, P<0.0001]. Among patients with GERD, 33.9% of subjects met Rome criteria compared to 13.5% of non-GERD patients (OR=3.6, 95% CI: 3.1-4.3, P<0.0001). Prevalence of all functional symptoms was higher in overlapping GERD and IBS subjects, when compared with their prevalence in the IBS subjects without GERD or GERD only subjects (P<0.05).CONCLUSION: This finding shows that in overlapping GERD and IBS, other functional abnormalities of the GI tract are also highly prevalent, suggesting a common underlying dysfunction.

Does a melatonin supplement alter the course of gastroesophageal reflux disease?

Symptomatic gastro-esophageal reflux disease(GERD) is a very common disease.The consequence of GERD is not only erosive esophagitis,but also esophageal stricture,Barrett's esophagus and extra-esophageal damage(including the lungs,throat,sinuses,middle ear and teeth).GERD and Barrett's esophagus are also identif ied as major risk factors for esophageal carcinoma.Therapy with melatonin prevents esophageal injury from acid-pepsin and acid-pepsin-bile exposure in animals,then further studies are required in humans to establish whether a melatonin supplement is able to protect the patients with GERD from erosions,Barrett's and neoplasia.

Nerve growth factor in muscle afferent neurons of peripheral artery disease and autonomic function

In peripheral artery disease patients,the blood supply directed to the lower limbs is reduced.This results in severe limb ischemia and thereby enhances pain sensitivity in lower limbs.The painful perception is induced and exaggerate during walking,and is relieved by rest.This symptom is termed by intermittent claudication.The limb ischemia also amplifies autonomic responses during exercise.In the process of pain and autonomic responses originating exercising muscle,a number of receptors in afferent nerves sense ischemic changes and send signals to the central nervous system leading to autonomic responses.This review integrates recent study results in terms of perspectives including how nerve growth factor affects muscle sensory nerve receptors in peripheral artery disease and thereby alters responses of sympathetic nerve activity and blood pressure to active muscle.For the sensory nerve receptors,we emphasize the role played by transient receptor potential vanilloid type 1,purinergic P2X purinoceptor 3 and acid sensing ion channel subtype 3 in amplified sympathetic nerve activity responses in peripheral artery disease.