Multiple Rapid Swallows (MRS) Complements Single-Swallow (SS) Analysis for High-Resolution Esophageal Manometry (HREM).

BACKGROUND: Multiple rapid swallows (MRS) during HREM assess post-deglutitive inhibition, LES relaxation, and subsequent esophageal contraction. AIMS: (1) To determine the relationship between MRS and single-swallow (SS) responses and (2) to determine if MRS provides information for symptomatic patients. METHODS: Healthy volunteers (HVs) and patients underwent HREM [30-s landmark, ten 5-mL SS, MRS (5 consecutive 2-mL swallows every 2-3 s)] and were analyzed with ManoView software version 3 with CC version 3.0. RESULTS: In 20 HVs, MRS response consisted of: (1) reduction in GEJ pressure; (2) absence of esophageal contractile activity during MRS; and (3) post-MRS peristaltic contraction greater than SS contractions. In 20 HVs and 403 patients, MRS IRP correlated with SS IRP (r = 0.65; p < 0.0001) and post-MRS contraction DCI correlated with SS DCI (r = 0.76; p < 0.0001). Abnormally elevated MRS IRP was seen in 68% type 2 achalasia, 50% type 3 achalasia, 47% EGJOO, and 9% jackhammer. Increased MRS DCI was seen in 53% type 2 achalasia, 92% type 3 achalasia, 10% EGJOO, 22% jackhammer, and 18% DES. Increased DCI post-MRS was seen in 38% patients with jackhammer, 8% type 3 achalasia, 12% EGJOO, and 9% DES. 14 out of 143 (10%) patients with normal or indeterminate results on SS analysis had at least one abnormality on MRS. CONCLUSIONS: MRS IRP correlated with SS IRP, and post-MRS DCI correlated with SS DCI. Patients with defined CC disorders have abnormalities on MRS. There were MRS abnormalities in some patients with normal SS studies, most notably suggesting impaired LES relaxation and/or spastic esophageal motility. MRS may complement the baseline SS study analysis.

Gastric Per Oral Endoscopic Myotomy (G-POEM) for the Treatment of Refractory Gastroparesis: Early Experience.

BACKGROUND: Gastric per oral endoscopic myotomy (G-POEM) of the pylorus is a technique that is recently being used to treat gastroparesis. Our aim was to report our experience in performing G-POEM for refractory gastroparesis of different etiologies and determine symptom improvement. METHODS: Thirteen patients undergoing G-POEM are reported. Pre- and post-procedure gastric emptying study (GES) and PAGI-SYM for symptom severity were obtained. Patients underwent G-POEM by creating a submucosal tunnel starting in the greater curvature of the distal antrum and extending it to the beginning of the duodenal bulb, followed by a full thickness pyloromyotomy. RESULTS: All 13 gastroparesis patients successfully underwent G-POEM (one diabetic [DGp], four idiopathic [IGp], eight postsurgical [PSGp]). Postsurgical patients included 4 s/p esophagectomy for esophageal cancer, 3 s/p Nissen fundoplication, and 1 s/p esophagectomy for achalasia. There were no procedure-related side effects. Of 11 patients completing follow-up questionnaires, eight were improved subjectively (four patients reported considerably better, four patients somewhat better, one unchanged, and two worse). Individual symptom severity scores tended to improve, particularly vomiting, retching, and loss of appetite. Of six patients that had post-G-POEM GES; GES improved in four, unchanged in one, and worsened in one). CONCLUSIONS: G-POEM for treatment of refractory gastroparesis appears to be a feasible and safe technique that can be successfully performed in patients with a variety of etiologies including different types of postsurgical gastroparesis. Our initial experience suggests that the majority of patients report some improvement in symptoms, particularly symptoms of vomiting, retching, and loss of appetite. Further experience is needed to determine the efficacy and safety of G-POEM and predict those who best respond to this treatment.

Preoperative risk factors for postoperative cardiac arrest following primary total hip and knee arthroplasty: A large database study.

BACKGROUND: Cardiac arrest (CA) has been identified as a potential complication following Total Hip Arthroplasty (THA) and Total Knee Arthroplasty (TKA). This retrospective, case-controlled study aims to identify risk factors in order to improve the management of patients undergoing THA or TKA with known preoperative comorbidities. METHODS: CPT codes were used to investigate the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database for patients who underwent THA or TKA from 2010 to 2017. Patients were classified as having cardiac arrest (CA) by the NSQIP guidelines. Patient samples with all possible covariates were included for the multivariate logistic regression analysis and assessed for independent association. RESULTS: Patients receiving perioperative transfusion, experiencing dyspnea with moderate exertion, dyspnea at rest, patients currently on dialysis, and patients aged ≥72 are all independently associated with increased rates of cardiac arrest (CA) following THA. Patients receiving perioperative transfusion, patients with anemia, bleeding disorders, dyspnea with moderate exertion, cardiac comorbidities, pulmonary comorbidities, and patients aged ≥73 are all associated with increased rates of cardiac arrest (CA) following TKA. CONCLUSION: Patients with the identified risk factors are at a greater risk of suffering cardiac arrest within 30 days following THA and TKA. It is imperative that we recognize which risk factors may precipitate CA in THA and TKA recipients so that prophylactic management can be employed. Furthermore, management guidelines should be updated for patients at high risk of CA following THA and TKA to prevent this complication.

Distal Esophageal Impedance Measured by High-resolution Esophageal Manometry With Impedance Suggests the Presence of Barrett's Esophagus.

Background/Aims: Barrett's esophagus (BE) is characterized by intestinal metaplasia in the distal esophagus. The aims of this study are to: (1) Compare baseline distal esophageal impedance (DEI) using high-resolution esophageal manometry with impedance (HREMI) in patients with BE, esophagitis, and healthy volunteers and (2) Correlate length of low impedance on HREMI in patients with BE to the length of endoscopic BE. Methods: Patients with BE or esophagitis who underwent HREMI were included. Ten volunteers had HREMI. Baseline DEI was calculated from HREMI using the landmark segment. In patients with BE, the impedance was plotted to measure the extent of plotted low impedance (PLI) and visual low impedance (VLI). Lengths of VLI and PLI were correlated to endoscopic length of BE by Prague score. Results: Forty-five patients were included (16 BE; 19 esophagitis; 10 volunteers). BE patients had lower baseline DEI at the first, second, and third sensors above the lower esophageal sphincter (mean ± SEM: 1.37 ± 0.45, 0.97 ± 0.27, and 0.81 ± 0.20) compared to volunteers (8.73 ± 0.60, 8.20 ± 0.73, and 6.94 ± 0.99; P < 0.001). Baseline DEI was lower in BE than esophagitis patients (2.98 ± 0.65, 2.49 ± 0.56, and 2.01 ± 0.51) at the first, second, and third sensors (P < 0.052 for second and third sensors); ie, BE < esophagitis < controls. PLI and VLI had a stronger correlation to circumferential score (r2 = 0.84 and 0.83) than maximal score (r2 = 0.76 and 0.68). Conclusions: Baseline DEI is lower in BE compared with esophagitis and healthy volunteers. The length of low impedance correlates to the endoscopic extent of BE. Thus, impedance values during HREMI may help suggest the presence and extent of BE or esophagitis.

Active presynaptic ribosomes in the mammalian brain, and altered transmitter release after protein synthesis inhibition.

Presynaptic neuronal activity requires the localization of thousands of proteins that are typically synthesized in the soma and transported to nerve terminals. Local translation for some dendritic proteins occurs, but local translation in mammalian presynaptic nerve terminals is difficult to demonstrate. Here, we show an essential ribosomal component, 5.8S rRNA, at a glutamatergic nerve terminal in the mammalian brain. We also show active translation in nerve terminals, in situ, in brain slices demonstrating ongoing presynaptic protein synthesis in the mammalian brain. Shortly after inhibiting translation, the presynaptic terminal exhibits increased spontaneous release, an increased paired pulse ratio, an increased vesicle replenishment rate during stimulation trains, and a reduced initial probability of release. The rise and decay rates of postsynaptic responses were not affected. We conclude that ongoing protein synthesis can limit excessive vesicle release which reduces the vesicle replenishment rate, thus conserving the energy required for maintaining synaptic transmission.

Post-Fundoplication Dumping Syndrome: A Frequent "Rare" Complication.

Gastroparesis, caused by delayed emptying of the stomach, has been shown to be associated with Nissen fundoplication. However, symptomatic rapid emptying of the stomach is rare after Nissen fundoplication, and its treatment is often challenging. We report 2 patients with dumping-like syndrome post-fundoplication with marked improvement of symptoms after dietary management and medical treatment.

Elevated methane levels in small intestinal bacterial overgrowth suggests delayed small bowel and colonic transit.

Limited research exists regarding the relationship between small intestinal bacterial overgrowth (SIBO), small bowel transit (SBT), and colonic transit (CT). Furthermore, symptom analysis is limited between the subtypes of SIBO: hydrogen producing (H-SIBO) and methane producing (M-SIBO). The primary aims of this study are to: compare the SBT and CT in patients with a positive lactulose breath test (LBT) to those with a normal study; compare the SBT and CT among patients with H-SIBO or M-SIBO; compare the severity of symptoms in patients with a positive LBT to those with a normal study; compare the severity of symptoms among patients with H-SIBO or M-SIBO.A retrospective review was performed for 89 patients who underwent a LBT and whole gut transit scintigraphy (WGTS) between 2014 and 2016. Seventy-eight patients were included. WGTS evaluated gastric emptying, SBT (normal ≥40% radiotracer bolus accumulated at the ileocecal valve at 6 hours), and CT (normal geometric center of colonic activity = 1.6-7.0 at 24 hours, 4.0-7.0 at 48 hours, 6.2-7.0 at 72 hours; elevated geometric center indicates increased transit). We also had patients complete a pretest symptom survey to evaluate nausea, bloating, constipation, diarrhea, belching, and flatulence.A total of 78 patients (69 females, 9 males, mean age of 48 years, mean BMI of 25.9) were evaluated. Forty-seven patients had a positive LBT (H-SIBO 66%, M-SIBO 34%). Comparison of SBT among patients with a positive LBT to normal LBT revealed no significant difference (62.1% vs 58.6%, P = .63). The mean accumulated radiotracer was higher for H-SIBO compared to M-SIBO (71.5% vs 44.1%; P < .05). For CT, all SIBO patients had no significant difference in geometric centers of colonic activity at 24, 48, and 72 hours when compared to the normal group. When subtyping, H-SIBO had significantly higher geometric centers compared to the M-SIBO group at 24 hours (4.4 vs 3.1, P < .001), 48 hours (5.2 vs 3.8, P = .002), and at 72 hours (5.6 vs 4.3, P = .006). The symptom severity scores did not differ between the positive and normal LBT groups. A higher level of nausea was present in the H-SIBO group when compared to the M-SIBO group.Overall, the presence of SIBO does not affect SBT or CT at 24, 48, and 72 hours. However, when analyzing the subtypes, M-SIBO has significantly more delayed SBT and CT when compared to H-SIBO. These results suggest the presence of delayed motility in patients with high methane levels on LBT.

Review: The Role of Cannabinoids on Esophageal Function-What We Know Thus Far.

The endocannabinoid system (ECS) primarily consists of cannabinoid receptors (CBRs), endogenous ligands, and enzymes for endocannabinoid biosynthesis and inactivation. Although the presence of CBRs, both CB1 and CB2, as well as a third receptor (G-protein receptor 55 [GPR55]), has been established in the gastrointestinal (GI) tract, few studies have focused on the role of cannabinoids on esophageal function. To date, studies have shown their effect on GI motility, inflammation and immunity, intestinal and gastric acid secretion, nociception and emesis pathways, and appetite control. Given the varying and sometimes limited efficacy of current medical therapies for diseases of the esophagus, further understanding and investigation into the interplay of the ECS on esophageal health and disease may present new therapeutic modalities that may help advance current treatment options. In this brief review, the current understanding of the ECS role in various esophageal functions and disorders is presented.

Mirtazapine for symptom control in refractory gastroparesis.

INTRODUCTION: Gastroparesis symptoms can be severe and debilitating. Many patients do not respond to currently available treatments. Mirtazapine has been shown in case reports to reduce symptoms in gastroparesis. AIM: To assess the efficacy and safety of mirtazapine in gastroparetic patients. METHODS: Adults with gastroparesis and poorly controlled symptoms were eligible. Participants were prescribed mirtazapine 15 mg PO qhs. Questionnaires containing the gastrointestinal cardinal symptom index (GCSI) and the clinical patient grading assessment scale (CPGAS) were completed by patients' pretreatment, at 2 weeks, and at 4 weeks. Primary end point was nausea and vomiting response to mirtazapine using the GCSI. Secondary end point was nausea and vomiting severity assessment using the CPGAS. P-values were calculated using the paired two-tailed Student's t-test. Intention to treat analysis was used. RESULTS: A total of 30 patients aged 19-86 years were enrolled. Of those, 24 patients (80%) completed 4 weeks of therapy. There were statistically significant improvements in nausea, vomiting, retching, and perceived loss of appetite at 2 and 4 weeks (all P-values <0.05) compared with pretreatment. There was a statistically significant improvement in the CPGAS score at week 2 (P=0.003) and week 4 (P<0.001). Of the total patients, 14 (46.7%) experienced adverse effects from mirtazapine and due to this, 6 patients stopped therapy. CONCLUSION: Mirtazapine significantly improved both nausea and vomiting in gastroparetics after 2 and 4 weeks of treatment. Side effects led to treatment self-cessation in a fifth of patients. From these data, we conclude that mirtazapine improves nausea and vomiting, among other symptoms, in patients with gastroparesis and might be useful in select patients.

Biofeedback therapy for chronic constipation in a patient with Prader-Willi syndrome.

Constipation is a common feature of Prader-Willi syndrome. Research exploring the prevalence, cause and treatment options for constipation is limited and lacks objective measurements such as anorectal manometry. We report a case of a 16-year-old lady with Prader-Willi syndrome presenting with rectal pain and constipation for 2 years despite multiple medications and weekly enemas. She also noted passive fecal incontinence that required frequent manual disimpactions. Anorectal manometry revealed an abnormal relaxation of the puborectalis and external sphincter muscles on push maneuvers suggesting dyssynergic defecation and rectal hypersensitivity. Contraction and relaxation of her pelvic muscles were recorded with electromyography. Relaxation of the puborectalis muscle improved significantly after three biofeedback sessions. Patient was successfully tapered off laxatives and has been maintained on linaclotide only. Dyssynergic defecation may be a common finding in Prader-Willi syndrome. In selected cases we recommend anorectal manometry to identify neuromuscular dysfunction and subsequent biofeedback therapy depending on the degree of mental retardation to minimize overuse of laxatives.

The Alzheimer's questionnaire: a proof of concept study for a new informant-based dementia assessment.

The aim of this pilot study is to determine the feasibility and clinical utility of a brief, informant-based screening questionnaire for Alzheimer's disease (AD) that can be administered in a primary care setting. The Alzheimer's Questionnaire (AQ) was administered to the informants of 188 patients in 3 dementia clinics (50 cognitively normal, 69 mild cognitive impairment (MCI), 69 AD). Total score for the AQ is based upon the sum of clinical symptom items in which the informant responds as being present. Clinical symptoms which are known to be highly predictive of the clinical AD diagnosis are given greater weight in the total AQ score. The mean time of administration of the AQ was 2.6 ± 0.6 minutes. Sensitivity and specificity were found to be high for detecting both AD (98.55, 96.00) and MCI (86.96, 94.00) with ROC curves yielding AUC values of 0.99 and 0.95, respectively. This pilot study indicates that the AQ is a brief, sensitive measure for detecting both MCI and AD and could be easily implemented in a primary care setting.

Anti-M: Report of two cases and review of literature.

Anti-M is a fairly common naturally occurring antibody with rarely causing hemolytic transfusion reactions or hemolytic disease of the newborn. Most anti-M are not active at 37 degrees C and can generally be ignored in transfusion practice. However, we did not find this antibody to be fairly common and detected only two cases of anti-M in the past three years. We describe these two cases; one 'immunizing' type and other 'naturally occurring' and review the literature. The immunizing type was reactive at 37 degrees C as well as AHG phase of testing with IgG component, and showing dosage effect while the other was 'naturally occurring' reactive well below 37 degrees C. Though rare, sometimes these antibodies can be of clinical significance when the antibody detected is reactive at 37 degrees C and AHG phase. When the antibody is active at 37 degrees C, M antigen negative cross match compatible red cell unit should be given.