The effect of age on the anatomy and function of the human colon is incompletely understood. The prevalence of disorders in adults such as constipation increase with age but it is unclear if this is ...due to confounding factors or age‐related structural defects. The aim of this study was to determine number and subtypes of enteric neurons and neuronal volumes in the human colon of different ages. Normal colon (descending and sigmoid) from 16 patients (nine male) was studied; ages 33–99. Antibodies to HuC/D, choline acetyltransferase (ChAT), neuronal nitric oxide synthase (nNOS), and protein gene product 9.5 were used. Effect of age was determined by testing for linear trends using regression analysis. In the myenteric plexus, number of Hu‐positive neurons declined with age (slope = −1.3 neurons/mm/10 years, P = 0.03). The number of ChAT‐positive neurons also declined with age (slope = −1.1 neurons/mm/10 years of age, P = 0.02). The number of nNOS‐positive neurons did not decline with age. As a result, the ratio of nNOS to Hu increased (slope = 0.03 per 10 years of age, P = 0.01). In the submucosal plexus, the number of neurons did not decline with age (slope = −0.3 neurons/mm/10 years, P = 0.09). Volume of nerve fibres in the circular muscle and volume of neuronal structures in the myenteric plexus did not change with age. In conclusion, the number of neurons in the human colon declines with age with sparing of nNOS‐positive neurons. This change was not accompanied by changes in total volume of neuronal structures suggesting compensatory changes in the remaining neurons.
The factors underlying the survival and maintenance of interstitial cells of Cajal (ICC) are not well understood. Loss of ICC is often associated with loss of neuronal nitric oxide synthase (nNOS) in ...humans, suggesting a possible link. The aim of this study was to determine the effect of neuronal NO on ICC in the mouse gastric body. The volumes of ICC were determined in nNOS−/− and control mice in the gastric body and in organotypic cultures using immunohistochemistry, laser scanning confocal microscopy and three‐dimensional reconstruction. ICC numbers were determined in primary cell cultures after treatment with an NO donor or an NOS inhibitor. The volumes of myenteric c‐Kit‐immunoreactive networks of ICC from nNOS−/− mice were significantly reduced compared with control mice. No significant differences in the volumes of c‐Kit‐positive ICC were observed in the longitudinal muscle layers. ICC volumes were either decreased or unaltered in the circular muscle layer after normalization for the volume of circular smooth muscle. The number of ICC was increased after incubation with S‐nitroso‐N‐acetylpenicillamine and decreased by N(G)‐nitro‐l‐arginine. Neuronally derived NO modulates ICC numbers and network volume in the mouse gastric body. NO appears to be a survival factor for ICC.
Background The pathogenesis of several common gastric motility diseases and functional GI disorders remains essentially unexplained. Gastric wall biopsies that include the muscularis propria to ...evaluate the enteric nervous system, interstitial cells of Cajal, and immune cells can provide important insights for our understanding of the etiology of these disorders. Objectives To determine the technical feasibility, reproducibility, and safety of performing a full-thickness gastric biopsy (FTGB) by using a submucosal endoscopy with mucosal flap (SEMF) technique; the technical feasibility, reproducibility, and safety of tissue closure by using an endoscopic suturing device; the ability to identify myenteric ganglia in resected specimens; and the long-term safety. Design Single center, preclinical survival study. Setting Animal research laboratory, developmental endoscopy unit. Subjects Twelve domestic pigs. Interventions Animals underwent an SEMF procedure with gastric muscularis propria resection. The resultant offset mucosal entry site was closed by using an endoscopic suturing device. Animals were kept alive for 2 weeks. Main Outcome Measurements The technical feasibility, reproducibility, and safety of the procedure; the clinical course of the animals; the histological and immunochemical evaluation of the resected specimen to determine whether myenteric ganglia were present in the sample. Results FTGB was performed by using the SEMF technique in all 12 animals. The offset mucosal entry site was successfully closed by using the suturing device in all animals. The mean resected tissue specimen size was 11 mm. Mean total procedure time was 61 minutes with 2 to 4 interrupted sutures placed per animal. Histology showed muscularis propria and serosa, confirming full-thickness resections in all animals. Myenteric ganglia were visualized in 11 of 12 animals. The clinical course was uneventful. Repeat endoscopy and necropsy at 2 weeks showed absence of ulceration at both the mucosal entry sites and overlying the more distal muscularis propria resection sites. There was complete healing of the serosa in all animals with minimal single-band adhesions in 5 of 12 animals. Retained sutures were present in 10 of 12 animals. Limitations Animal experiment. Conclusions FTGB by using the SEMF technique and an endoscopic suturing device is technically feasible, reproducible, and safe. Larger tissue specimens will allow improved analysis of multiple cell types.
Background Cellular changes associated with diabetic (DG) and idiopathic gastroparesis (IG) have recently been described from patients enrolled in the Gastroparesis Clinical Research Consortium. The ...association of these cellular changes with gastroparesis symptoms and gastric emptying is unknown. The aim of this study was to relate cellular changes to symptoms and gastric emptying in patients with gastroparesis.
Methods Earlier, using full thickness gastric body biopsies from 20 DG, 20 IG, and 20 matched controls, we found decreased interstitial cells of Cajal (ICC) and enteric nerves and an increase in immune cells in both DG and IG. Here, demographic, symptoms gastroparesis cardinal symptom index score (GCSI), and gastric emptying were related to cellular alterations using Pearson’s correlation coefficients.
Key Results Interstitial cells of Cajal counts inversely correlated with 4 h gastric retention in DG but not in IG (r = −0.6, P = 0.008, DG, r = 0.2, P = 0.4, IG). There was also a significant correlation between loss of ICC and enteric nerves in DG but not in IG (r = 0.5, P = 0.03 for DG, r = 0.3, P = 0.16, IG). Idiopathic gastroparesis with a myenteric immune infiltrate scored higher on the average GCSI (3.6 ± 0.7 vs 2.7 ± 0.9, P = 0.05) and nausea score (3.8 ± 0.9 vs 2.6 ± 1.0, P = 0.02) as compared to those without an infiltrate.
Conclusions & Inferences In DG, loss of ICC is associated with delayed gastric emptying. Interstitial cells of Cajal or enteric nerve loss did not correlate with symptom severity. Overall clinical severity and nausea in IG is associated with a myenteric immune infiltrate. Thus, full thickness gastric biopsies can help define specific cellular abnormalities in gastroparesis, some of which are associated with physiological and clinical characteristics of gastroparesis.
Background The etiology of several common gastric motility diseases remains largely unknown. Gastric wall biopsy specimens that include the muscularis propria to evaluate the enteric nervous system, ...interstitial cells of Cajal, and related cells are essential to promote our understanding of the pathophysiologic mechanisms. On the basis of our previous work, a double EMR technique provided sufficient tissue to identify myenteric ganglia. A serious limitation to the technique was the resultant gastric wall perforation after tissue resection. The optimal procedure would seal the gastric wall defect before tissue resection, eliminating the risk of peritonitis. Objectives The aims of this study were to (1) determine the technical feasibility and reproducibility of a full-thickness gastric biopsy by use of a novel double EMR technique without creating a perforation (“no hole”) and to (2) determine safety of the procedure. Design and Interventions Preclinical study of 6 pigs. Each animal underwent a “no hole” double EMR survival procedure. To prevent perforation, detachable endoloops and prototype T-tag tissue anchors were placed before resection. At 2 weeks repeat endoscopy was performed followed by necropsy. Main Outcome Measurements Hematoxylin-eosin staining was used to determine which muscle layers were included in the resected specimen, and an antibody to neuronal nitric oxide synthase was used to visualize myenteric ganglia in the sample. Technical feasibility, reproducibility, and safety of the procedure were evaluated. Results Full-thickness gastric biopsy specimens were obtained from all animals without overt perforation. There were no procedural complications. Histologic examination showed muscularis propria with all layers of muscle present, and immunochemical studies demonstrated myenteric ganglia in all tissue samples. Four animals had an uneventful clinical course, and repeat endoscopy at week 2 showed ulceration with stellate fibrosis. Necropsy showed mild localized adhesions. Two animals were killed at days 3 and 6, respectively, because of suspected peritonitis. At necropsy, delayed perforations at the resection sites were noted with displaced endoloops and tissue anchors. Conclusion This study explored the concept of obtaining deep muscle wall biopsy specimens with use of a unique approach of resection without perforation. The novel “no hole” double EMR technique was technically feasible and reproducible with sufficient tissue obtained to identify myenteric ganglia. However, there was a high delayed perforation rate associated with displaced endoloops and tissue anchors. On the basis of this early experience, improved safety data may be anticipated with future studies using improved tissue closure devices.
The aim of this study was to develop a decision support tool for nurses to facilitate aging in place of people with dementia and to test its usability.
Nurses play an important role in detecting ...practical problems preventing persons with dementia (PwD) from aging in place and advising them on possible solutions. These are complex and challenging tasks for nurses.
A mixed methods study was conducted. The content development of the App comprised a literature and internet search, and individual and group interviews with professionals (n = 8) and researchers (n = 5). The technical development was an iterative process in which usability was tested by the project team (n = 4), experts (n = 6), and end-users (n = 9), using heuristic evaluation, a think-aloud approach, and a questionnaire (PSSUQ).
The App contains a structured problem assessment for three problem domains—self-reliance, safety, and informal care—based on validated questionnaires and self-formulated questions. The problem assessment is linked to an overview of possible solutions for the problems detected. Three prototypes have been developed. The users of the third prototype were overall satisfied with the App as they scored on average 1.7 on the PSSUQ (range 1–7 and lower scores indicating higher satisfaction).
A user-friendly prototype of the decision support App is now available. Users indicated to be very willing to use to App in daily practice. However, besides further technical development, implementation of the App into practice requires evidence supporting its efficacy, feasibility and effectiveness.
Patients undergoing chronic hemodialysis were among the first to receive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccinations because of their increased risk for severe ...coronavirus disease and high case-fatality rates. By using a previously reported cohort from Germany of at-risk hemodialysis patients and healthy donors, where antibody responses were examined 3 weeks after the second vaccination, we assessed systemic cellular and humoral immune responses in serum and saliva 4 months after vaccination with the Pfizer-BioNTech BNT162b2 vaccine using an interferon-γ release assay and multiplex-based IgG measurements. We further compared neutralization capacity of vaccination-induced IgG against 4 SARS-CoV-2 variants of concern (Alpha, Beta, Gamma, and Delta) by angiotensin-converting enzyme 2 receptor-binding domain competition assay. Sixteen weeks after second vaccination, compared with 3 weeks after, cellular and humoral responses against the original SARS-CoV-2 isolate and variants of concern were substantially reduced. Some dialysis patients even had no detectable B- or T-cell responses.
Background
Wireless motility capsule (WMC) findings are incompletely defined in suspected gastroparesis. We aimed to characterize regional WMC transit and contractility in relation to scintigraphy, ...etiology, and symptoms in patients undergoing gastric emptying testing.
Methods
A total of 209 patients with gastroparesis symptoms at NIDDK Gastroparesis Consortium centers underwent gastric scintigraphy and WMCs on separate days to measure regional transit and contractility. Validated questionnaires quantified symptoms.
Key Results
Solid scintigraphy and liquid scintigraphy were delayed in 68.8% and 34.8% of patients; WMC gastric emptying times (GET) were delayed in 40.3% and showed 52.8% agreement with scintigraphy; 15.5% and 33.5% had delayed small bowel (SBTT) and colon transit (CTT) times. Transit was delayed in ≥2 regions in 23.3%. Rapid transit was rarely observed. Diabetics had slower GET but more rapid SBTT versus idiopathics (P ≤ .02). GET delays related to greater scintigraphic retention, slower SBTT, and fewer gastric contractions (P ≤ .04). Overall gastroparesis symptoms and nausea/vomiting, early satiety/fullness, bloating/distention, and upper abdominal pain subscores showed no relation to WMC transit. Upper and lower abdominal pain scores (P ≤ .03) were greater with increased colon contractions. Constipation correlated with slower CTT and higher colon contractions (P = .03). Diarrhea scores were higher with delayed SBTT and CTT (P ≤ .04).
Conclusions & Inferences
Wireless motility capsules define gastric emptying delays similar but not identical to scintigraphy that are more severe in diabetics and relate to reduced gastric contractility. Extragastric transit delays occur in >40% with suspected gastroparesis. Gastroparesis symptoms show little association with WMC profiles, although lower symptoms relate to small bowel or colon abnormalities.
Wireless motility capsule (WMC) findings in suspected gastroparesis and relations to symptoms have been poorly defined. Evaluation of patients with gastroparesis symptoms revealed gastric emptying delays with WMCs that were similar to scintigraphy, were related to reduced contractility, and were often associated with extragastric or generalized transit delays; symptoms correlated poorly with WMC profiles. These findings provide insight into motor abnormalities in gastroparesis pathogenesis and form a basis for future investigations studying the impact of WMC testing on clinical care.
Background A major barrier to furthering our understanding of the pathophysiology of neuromuscular GI diseases, including functional GI disorders, is the inability to obtain deep gastric-wall biopsy ...specimens that include both layers of the muscularis propria, which allows evaluation of specific cell types, including myenteric ganglia. Objectives The aims of this preclinical study were to (1) evaluate different endoscopic approaches for obtaining deep gastric-muscle–wall biopsy specimens and (2) determine if myenteric ganglia were present in the tissue samples. Design and Interventions This was a preclinical acute study by using a pig model. Multiple samples were obtained from 4 pigs. The endoscopic techniques evaluated were (1) EUS-guided tru-cut biopsy of the gastric wall, (2) jumbo biopsy of the post-EMR site, (3) jumbo biopsy of the gastrotomy margin, (4) serosal-side biopsy through a gastrotomy, and (5) double-EMR resection. Main Outcome Measurements Resected tissue was submitted for histology to determine which wall layers were included in the resected specimen. Hematoxylin and eosin staining was used to determine which muscle layers were biopsied, and an antibody to protein gene product 9.5 was used to determine if myenteric ganglia were present in the sample. Results Seventy-two tissue samples were obtained: EUS-guided tru-cut biopsy (n = 16), jumbo biopsy of the post-EMR site (n = 16), jumbo biopsy of the gastrotomy (n = 16), serosal-side biopsy (n = 16), and double-EMR resection (n = 8). Only the double-EMR resection tissues showed the presence of longitudinal muscle, indicating the presence of both muscle layers and the myenteric plexus. Immunofluorescence studies demonstrated the presence of myenteric ganglia only in the double-EMR tissues and in none of the other gastric samples. No adjacent organs were included in the resection. Conclusions The double-EMR technique was the only studied technique that resulted in a deep gastric-wall sample and provided sufficient tissue to evaluate both muscle layers and the intermuscular layer that contain myenteric ganglia. Further studies are needed to verify the efficacy and to assess the safety of this approach.
Purpose
To evaluate the incidence of acute renal failure and chronic kidney disease due to occlusion of accessory renal arteries during endovascular aneurysm repair of infrarenal abdominal aortic ...aneurysm.
Material and Methods
We retrospectively reviewed the course of 181 patients (mean age, 71, SD ± 9 years) who underwent EVAR of infrarenal abdominal aortic aneurysm. The renal vessel anatomy was analyzed in all pre- and postoperative CT scans. Diameter and origin of accessory renal arteries were evaluated. Renal function was determined by pre- and postoperative serum creatinine and eGFR levels. Long-term follow-up (>3 months) of patients was available in 121 cases (66.9%). Acute kidney injury and chronic kidney failure were defined according to guidelines of “Kidney Disease: Improving Global Outcomes” (KDIGO).
Results
In 65 of 181 patients (33.9%), 82 accessory renal arteries were identified preoperatively. In 19 of 181 patients (10.5%), one or more accessory renal arteries were covered and subsequently occluded by the implanted stent-graft device. Neither acute kidney injury (10.3% vs 12.5%;
p
= .785) nor chronic kidney disease (10.7% vs 15.38%;
p
= .452) was detected significantly more often in patients with covered accessory renal artery. The only significant predictor of acute kidney injury was the preoperative serum creatinine level (1.12 mg/dl vs. 0.98 mg/dl;
p
= .03). Significant predictors for chronic kidney disease were preoperative serum creatinine, eGFR, and impaired renal function (
p
< .001).
Conclusion
Coverage of accessory renal artery due to stent-graft does not lead either to temporary acute kidney injury after endovascular aneurysm repair or to chronic kidney disease.
Level of Evidence
Level II b.
PDF
