The structure of EXTL3 helps to explain the different roles of bi-domain exostosins in heparan sulfate synthesis.

Heparan sulfate is a highly modified O-linked glycan that performs diverse physiological roles in animal tissues. Though quickly modified, it is initially synthesised as a polysaccharide of alternating ß-D-glucuronosyl and N-acetyl-α-D-glucosaminyl residues by exostosins. These enzymes generally possess two glycosyltransferase domains (GT47 and GT64)-each thought to add one type of monosaccharide unit to the backbone. Although previous structures of murine exostosin-like 2 (EXTL2) provide insight into the GT64 domain, the rest of the bi-domain architecture is yet to be characterised; hence, how the two domains co-operate is unknown. Here, we report the structure of human exostosin-like 3 (EXTL3) in apo and UDP-bound forms. We explain the ineffectiveness of EXTL3's GT47 domain to transfer ß-D-glucuronosyl units, and we observe that, in general, the bi-domain architecture would preclude a processive mechanism of backbone extension. We therefore propose that heparan sulfate backbone polymerisation occurs by a simple dissociative mechanism.

Cortical processing to anorectal stimuli after rectal resection with and without radiotherapy.

BACKGROUND: Bowel dysfunction is common after surgery for rectal cancer, especially when neoadjuvant radiotherapy is used. The role of sensory function in the pathogenesis remains obscure, and the aim of the present study was to characterize the sensory pathways of the brain-gut axis in rectal cancer patients treated with resection ± radiotherapy compared with healthy volunteers. METHODS: Sensory evaluation by (neo)rectal distensions was performed and sensory evoked potentials (SEPs) were recorded during rapid balloon distensions of the (neo)rectum and anal canal in resected patients with (n = 8) or without (n = 12) radiotherapy. Twenty healthy volunteers were included for comparison. (Neo)rectal latencies and amplitudes of SEPs were compared and spectral band analysis from (neo)rectal and anal distensions was used as a proxy of neuronal processing. RESULTS: Neorectal sensation thresholds were significantly increased in both patient categories (all p < 0.008). There were no differences in (neo)rectal SEP latencies and amplitudes between groups. However, spectral analysis of (neo)rectal SEPs showed significant differences between all groups in all bands (all p < 0.01). On the other hand, anal SEP analyses only showed significant differences between the delta (0-4 Hz), theta (4-8 Hz) and, gamma 32-50 Hz) bands (all p < 0.02) between the subgroup of patients that also received radiotherapy and healthy volunteers. CONCLUSIONS: Surgery for rectal cancer leads to abnormal cortical processing of neorectal sensation. Additional radiotherapy leads to a different pattern of central sensory processing of neorectal and anal sensations. This may play a role in the functional outcome of these patients.

Evaluation of novel multiplex qPCR assays for diagnosis of pathogens associated with the bovine respiratory disease complex.

Bovine respiratory disease complex is the most common disease requiring the use of antimicrobials in industrial calf production worldwide. Pathogenic bacteria (Mannheimia haemolytica (Mh), Pasteurella multocida (Pm), Histophilus somni (Hs), and Mycoplasma bovis) and a range of viruses (bovine respiratory syncytial virus, bovine coronavirus, bovine parainfluenza virus type 3, bovine viral diarrhea virus and bovine herpesvirus type 1) are associated with this complex. As most of these pathogens can be present in healthy and diseased calves, simple detection of their presence in diseased calves carries low predictive value. In other multi-agent diseases of livestock, quantification of pathogens has added substantially to the predictive value of microbiological diagnosis. The aim of this study was to evaluate the ability of two recently developed quantitative PCR (qPCR) kits (Pneumo4B and Pneumo4V) to detect and quantify these bacterial and viral pathogens, respectively. Test efficiencies of the qPCR assays, based on nucleic acid dilution series of target bacteria and viruses, were 93-106% and 91-104%, respectively, with assay detection limits of 10-50 copies of nucleic acids. All 44 strains of target bacteria were correctly identified, with no false positive reactions in 135strains of non-target bacterial species. Based on standard curves of log10 CFU versus cycle threshold (Ct) values, quantification was possible over a 5-log range of bacteria. In 92 tracheal aspirate samples, the kappa values for agreement between Pneumo4B and bacterial culture were 0.64-0.84 for Mh, Pm and Hs. In an additional 84 tracheal aspirates, agreement between Pneumo4B or Pneumo 4V and certified diagnostic qPCR assays was moderate (0.57) for M. bovis and high (0.71-0.90) for viral pathogens. Thus Pneumo4 kits specifically detected and quantified the relevant pathogens.

The economic impact of drying off cows with a dry-off facilitator (cabergoline) compared with 2 methods of gradual cessation of lactation for European dairy farms.

An abrupt method to dry off cows has disadvantages and is considered inappropriate for current dairy cows due to welfare issues and risks for intramammary infections (IMI). A gradual cessation of lactation (by feeding or milking frequency reduction) has been the generally recommended method for drying off cows to prevent these adverse effects. However, a new alternative to the gradual approach is to abruptly stop milking at the same time as using cabergoline (CAB), a prolactin inhibitor. The aim of the study was to compare the net costs of 3 different methods of drying off cows [gradual reduction in feed (referred to as gradual feeding), gradual reduction in milking frequency (referred to as gradual milking), and abrupt cessation of milking with CAB]. A stochastic Monte Carlo simulation model, at cow level, was developed to calculate the net costs of applying these methods. All inputs for the model were based on literature information, authors' expertise, and expert knowledge. The net costs were determined by only including costs and benefits, which varied between the 3 methods. The model simulated a cow from 7 d before the day of drying off until the end of the next lactation. The likelihood of whether a cow was leaking milk early in the dry period was determined. Subsequently, it was determined whether or not the cow will get an IMI during the dry period, where the probability of getting an IMI was higher for cows leaking milk than for cows not leaking milk. If the IMI was not cured during the dry period, the cow had an IMI at calving. Also, milk production and feed requirements were modeled, and labor for applying the drying off method was included. For all methods, the net costs were calculated as the sum of costs for feed during the gradual feed reduction period, costs for applying the gradual-milking method, and the IMI costs during the dry period and lactation, minus the milk revenues during the transition from lactation to the dry period. Under default conditions, the average net cost of abrupt cessation of milking with CAB was €49.6/cow. The data showed that 90% of the net costs ranged from -€13.7 to €307.8/cow. The average net costs for gradual feeding and gradual milking were €99.1 and €71.5/cow, respectively. In conclusion, abrupt cessation of milking with CAB saved €49.5 and €21.9/cow on average compared with gradual feeding and gradual milking, respectively. This difference was mainly due to more milk returns and lower labor and IMI costs during lactation.

Long-term effect of medical treatment of diarrhoea in 377 patients with SeHCAT scan diagnosed bile acid malabsorption from 2003 to 2016; a retrospective study.

BACKGROUND: Excessive amounts of bile acids entering the colon due to bile acid malabsorption cause chronic bile acid diarrhoea. Diagnosis is possible by measuring the retention fraction of orally ingested 75 Selenium homotaurocholic acid (SeHCAT). The knowledge of long-term effects of medical treatment is sparse. AIM: To describe diarrhoea, adherence to treatment, treatment effects and quality of life in a large, well-defined cohort of patients with bile acid diarrhoea. METHODS: A retrospective survey was performed among 594 patients with bile acid malabsorption verified by SeHCAT scans at our unit between 2003 and 2016. Questionnaires about medical history, diarrhoea, use of medication, and quality of life scores were mailed to all patients. RESULTS: Among 594 patients 377 (69%) responded. Among respondents, 121 (32%) had bile acid diarrhoea due to ileal disease or resection (type 1), 198 (52%) idiopathic bile acid diarrhoea (type 2) and 58 (16%) bile acid diarrhoea due to other non-ileal disease, mainly cholecystectomy (type 3). At follow-up, half of the patients, 184 (50%), reported improvement of diarrhoea. However, 273 patients (74%) still reported diarrhoea and 234 (62%) regularly used anti-diarrhoeal medication. In spite of treatment, 235 (64%) considered reduced quality of life by diarrhoea and 184 (50%) reported that diarrhoea was unaltered or worse than before established diagnosis. CONCLUSION: Many patients with bile acid diarrhoea continue to have bothersome diarrhoea in spite of correct diagnosis and treatment.

Microstructural white matter brain abnormalities in patients with idiopathic fecal incontinence.

BACKGROUND: Abnormal central nervous system processing of visceral sensation may be a part of the pathogenesis behind idiopathic fecal incontinence (IFI). Our aim was to characterize brain differences in patients with IFI and healthy controls by means of structural magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI). METHODS: In 21 female patients with IFI and 15 female healthy controls, whole-brain structural differences in gray matter volume (GMV), cortical thickness, and white matter tracts fractional anisotropy (FA) were quantified. For this purpose, we used voxel-based morphometry, surface based morphometry and tract-based spatial statistic, respectively. Furthermore, associations between structural brain characteristics and latencies of rectal sensory evoked electroencephalography potentials were determined. KEY RESULTS: Compared to healthy controls, IFI patients had significantly reduced FA values, reflecting reduced white matter tract integrity, in the left hemisphere superior longitudinal fasciculus (SLF), posterior thalamic radiation, and middle frontal gyrus (MFG), all P<.05. No differences were observed in GMV or in cortical thickness. The reduced FA values in the SLF and MFG were correlated with prolonged latencies of cortical potentials evoked by rectal stimuli (all P<.05). CONCLUSIONS & INFERENCES: This explorative study suggests that IFI patients have no macrostructural brain changes, but exhibit microstructural changes in white matter tracts relevant for sensory processing. The clinical relevance of this finding is supported by its correlations with prolonged latencies of cortical potentials evoked by rectal stimulation. This supports the theories of central nervous system changes as part of the pathogenesis in IFI patients.

Skills among young and elderly laypersons during simulated dispatcher assisted CPR and after CPR training.

BACKGROUND: Dispatcher assisted cardiopulmonary resuscitation (DA-CPR) increase the rate of bystander CPR. The aim of the study was to compare the performance of DA-CPR and attainable skills following CPR training between young and elderly laypersons. METHODS: Volunteer laypersons (young: 18-40 years; elderly: > 65 years) participated. Single rescuer CPR was performed in a simulated DA-CPR cardiac arrest scenario and after CPR training. Data were obtained from a manikin and from video recordings. The primary endpoint was chest compression depth. RESULTS: Overall, 56 young (median age: 26, years since last CPR training: 6) and 58 elderly (median age: 72, years since last CPR training: 26.5) participated. Young laypersons performed deeper (mean (SD): 56 (14) mm vs. 39 (19) mm, P < 0.001) and faster (median (25th-75th percentile): 107 (97-112) per min vs. 84 (74-107) per min, P < 0.001) chest compressions compared to elderly. Young laypersons had shorter time to first compression (mean (SD): 71 (11) seconds vs. 104 (38) seconds, P < 0.001) and less hands-off time (median (25th-75th percentile): 0 (0-1) seconds vs. 5 (2-10) seconds, P < 0.001) than elderly. After CPR training chest compressions were performed with a depth (mean (SD): 64 (8) mm vs. 50 (14) mm, P < 0.001) and rate (mean (SD): 111 (11) per min vs. 93 (18) per min, P < 0.001) for young and elderly laypersons respectively. CONCLUSION: Despite long CPR retention time for both groups, elderly laypersons had longer retention time, and performed inadequate DA-CPR compared to young laypersons. Following CPR training the attainable CPR level was of acceptable quality for both young and elderly laypersons.

Reliability, validity and sensitivity to change of neurogenic bowel dysfunction score in patients with spinal cord injury.

STUDY DESIGN: Psychometrics study. OBJECTIVES: The aim of this study is to investigate the validity, reliability and sensitivity to change of neurogenic bowel dysfunction (NBD) score. SETTING: Dokuz Eylül University Faculty of Medicine, Turkey. METHODS: The study included 42 patients with spinal cord injury (SCI). The reliability of NBD score was assessed by test-retest reliability and internal consistency. Cronbach's alpha coefficient was calculated to determine internal consistency. The construct validity was evaluated by exploring correlations between the NBD score and SF-36 scales, patient assessment of impact of NBD on quality of life (QoL) and the physician global assessment (PGA). The Global Rating of Change (GRC) scale was used to assess the change of NBD to investigate the sensitivity of the score to change. RESULTS: Cronbach's alpha coefficient was 0.547. In test-retest reliability analysis, high correlations between total test-retest NBD score and answers of each question were found (r=1.000, P<0.001). NBD score had a strong and significant correlation with PGA (r=0.98, P<0.000) and the impact on QoL (r=0.92, P<0.001). There was a significant negative correlation between NBD score and subscales of SF-36 (P<0.05) except physical functioning, physical role functioning and physical component summary score. There was a significant improvement in NBD scores after treatment (P=0.011). A significant positive correlation was found between GRC scale and change in total NBD score (r=0.821, P=0.007). CONCLUSION: The Turkish version of the NBD score is a valid and reliable instrument and also sensitive to change in patients with SCI.

Assessment of colorectal length using the electromagnetic capsule tracking system: a comparative validation study in healthy subjects.

AIM: We aimed to determine colorectal length with the 3D-Transit system by describing a 'centreline' of capsule movement and comparing it with known anatomy, as determined by magnetic resonance imaging (MRI). Further, we aimed to test the day-to-day variation of colorectal length assessed with the system. METHOD: The 3D-Transit system consists of electromagnetic capsules that can be tracked as they traverse the gastrointestinal tract. Twenty-five healthy subjects were examined with both 3D-Transit and MRI. Another 21 healthy subjects were examined with 3D-Transit on two consecutive days. RESULTS: Computation of colorectal length from capsule passage was possible for 60 of the 67 3D-Transit recordings. The length of the colorectum measured with MRI and 3D-Transit was 95 (75-153) cm and 99 (77-147) cm, respectively (P = 0.15). The coefficient of variation (CV) between MRI and 3D-Transit was 7.8%. Apart from the caecum/ascending colon being 26% (P = 0.002) shorter on MRI, there were no other differences in total or segmental colorectal lengths between methods (all P > 0.05). The length of the colorectum measured with 3D-Transit on two consecutive days was 102 (73-119) cm and 103 (75-123) cm (P = 0.67). The CV between days was 7.3%. CONCLUSION: The 3D-Transit system allows accurate and reliable determination of colorectal length compared with MRI-derived colorectal length and between days. Antegrade or retrograde capsule movement relative to this centreline, as well as the length and speed of movements, may be determined by future studies to allow better classification and treatment in patients with dysmotility.

Management of chronic constipation in adults.

Chronic constipation (CC) is an extremely common condition with an estimated prevalence of up to 24%. Most patients with CC should be treated in primary care. Changes in lifestyle, including increased intake of dietary fibre, fluid, and exercise, should be attempted in most patients. Osmotic or stimulant laxatives are indicated if there are insufficient effects of lifestyle changes. Prokinetics and secretagogues should be restricted to those not responding to basic treatment. Anorectal physiology tests and assessment of colorectal transit time are indicated if medical treatment fails or if symptoms indicate severely obstructed defecation. If symptoms indicate an underlying structural disorder, barium or magnetic resonance evacuation proctography is indicated. Biofeedback therapy is effective in patients with dyssynergic defecation. In patients with other evacuation disorders, rectally administered laxatives or transanal irrigation should be attempted. Surgery is restricted to the minority of CC patients with very severe symptoms not responding to conservative treatment.

Esophagogastric junction in systemic sclerosis: A study with the functional lumen imaging probe.

BACKGROUND: Fibrosis and atrophy of esophageal smooth muscle cells cause gastro-esophageal reflux and dysphagia in most patients with systemic sclerosis (SSc). Recent studies indicate that distensibility of the esophagogastric junction (EGJ), assessed with the Functional Lumen Imaging Probe (FLIP) may be a more sensitive and accurate measure of sphincter function than manometry. We aim to describe and compare distension parameters of the EGJ in a well-characterized group of patients with SSc. METHOD: Twelve patients with SSc reporting reflux or dysphagia (11 women, median age 53 [range 35-72], duration of disease: 1-20 years) were investigated using distensibility testing of the EGJ. Patients were compared with 11 healthy volunteers (HV) (10 women, median age 53 [range 40-68]). The pressure and minimum diameter along the EGJ during ramp distension were used for distensibility analysis. KEY RESULTS: Patients with SSc had significantly lower EGJ yield pressure (median: 4.0 mm Hg [Inter Quartile Range (IQR): 2.8-7.7]) than HV (median: 6.2 mm Hg [IQR: 9.4-26]) (P=.007). Likewise, the pressure-strain elastic modulus was lower in SSc patients (median 1.73 kPa [IQR: 1.16-2.15]) than in HV (median 2.41 kPa [IQR: 1.85-2.67]) (P=.03), indicating the reduced resistance to distension in SSc patient. CONCLUSION & INFERENCES: Patients with SSc and symptoms of reflux and dysphagia have significantly reduced resistance to distension of the EGJ.

Ageing with neurogenic bowel dysfunction.

STUDY DESIGN: Longitudinal study with postal survey. OBJECTIVES: To describe changes in the patterns of neurogenic bowel dysfunction and bowel management in a population of people with spinal cord injury (SCI) followed for two decades. SETTING: Members of the Danish SCI Association. METHODS: In 1996, a validated questionnaire on bowel function was sent to the members of the Danish SCI Association (n=589). The same questionnaire was sent to all the surviving members in 2006 (n=284) and in 2015 (n=178). A total of 109 responded to both the 1996 and 2015 questionnaires. RESULTS: Comparing data from 2015 with those from the exact same participants in 1996, the proportion of respondents needing more than 30 min for each defaecation increased from 21 to 39% (P<0.01), the use of laxatives increased (P<0.05) and the proportion considering themselves very constipated increased from 19 to 31% (P<0.01). In contrast, the proportion suffering from faecal incontinence remained stable at 18% in 1996 and 19% in 2015. During the 19-year period, there had been no significant change in the methods for bowel care, but 22 (20%) had undergone surgery for bowel dysfunction, including 11 (10%) who had some form of stoma. CONCLUSION: Self-assessed severity of constipation increased but quality of life remained stable in a cohort of people with SCI followed prospectively for 19 years. Methods for bowel care remained surprisingly stable but a large proportion had undergone stoma surgery.

International spinal cord injury bowel function basic data set (Version 2.0).

STUDY DESIGN: International expert working group. OBJECTIVES: To revise the International Spinal Cord Injury (SCI) Bowel Function Basic Data Set as a standardized format for the collecting and reporting of a minimal amount of information on bowel function in clinical practice and research. SETTING: Working group appointed by the American Spinal injury association (ASIA) and the International Spinal Cord Society (ISCoS). METHODS: The draft prepared by the working group was reviewed by the International SCI Data Set Committee and later by members of the ISCoS Executive and Scientific Committees and the ASIA board. The revised data set was posted on the ASIA and ISCoS websites for 1 month to allow further comments and suggestions. Changes resulting from a Delphi process among experts in children with SCI were included. Members of ISCoS Executive and Scientific Committees and the ASIA board made a final review and approved the data set. RESULTS: The International SCI Bowel Function Basic Data Set (Version 2.0) consists of the following 16 items: date of data collection, gastrointestinal and anal sphincter dysfunction unrelated to SCI, surgical procedures on the gastrointestinal tract, defecation method and bowel-care procedures, average time required for defecation, frequency of defecation, uneasiness, headache or perspiration during defecation, digital stimulation or evacuation of the anorectum, frequency of fecal incontinence, flatus incontinence, need to wear pad or plug, oral laxatives and prokinetics, anti-diarrheal agents, perianal problems, abdominal pain and discomfort and the neurogenic bowel dysfunction score. CONCLUSION: The International SCI Bowel Function Basic Data Set (Version 2.0) has been developed.

Presence and localization of bacteria in the bovine endometrium postpartum using fluorescence in situ hybridization.

The aim of this study was to investigate bacterial invasiveness of the bovine endometrium during the postpartum period. Fluorescence in situ hybridization was applied to endometrial biopsies using probes for Fusobacterium necrophorum, Porphyromonas levii, Trueperella pyogenes, Escherichia coli and a probe for bacteria in general (the overall domain Bacteria) to determine their tissue localization. Holstein cows were sampled at three time points postpartum (T1: 4-12 days postpartum, T2: 24-32 days postpartum and T3: 46-54 days postpartum). At T1, cows were clinically scored as having a uterine infection based on presence of a brownish, fetid vaginal discharge or as normal if having normal lochia. An endometrial biopsy was taken from all cows at T1 (n = 57). Endometrial biopsies were taken from the same cows at T2 and T3 if allowed by the size of the cervical canal and if the cow had not been inseminated. Fifty and 39 biopsies were obtained at T2 and T3, respectively. The biopsies were evaluated for inflammation and for presence and localization of bacteria. When analyzed by the probe for the entire domain Bacteria, bacteria were found in most biopsies irrespectively of time (T1: 79.0%, T2: 82.0%, T3: 89.7%). Fusobacterium necrophorum and Porphyromonas levii were often present in the endometrium at T1 (61.1% and 47.8%, respectively), but the prevalence decreased significantly over time. Trueperella pyogenes and Escherichia coli were less prevalent at T1 (8.8% and 10.5%, respectively) and their prevalence also decreased significantly over time. Fusobacterium necrophorum and Porphyromonas levii were often co-localized intraepithelially or in the lamina propria. Trueperella pyogenes and Escherichia coli were located only on the endometrial surface. Due to the high prevalence of tissue invasiveness, these findings emphasize the importance of Fusobacterium necrophorum and Porphyromonas levii in postpartum uterine disease of cattle and indicate that tissue invasiveness is an important aspect of the pathogenesis.

Established and emerging methods for assessment of small and large intestinal motility.

BACKGROUND: Gastrointestinal symptoms are common in the general population and may originate from disturbances in gut motility. However, fundamental mechanistic understanding of motility remains inadequate, especially of the less accessible regions of the small bowel and colon. Hence, refinement and validation of objective methods to evaluate motility of the whole gut is important. Such techniques may be applied in clinical settings as diagnostic tools, in research to elucidate underlying mechanisms of diseases, and to evaluate how the gut responds to various drugs. A wide array of such methods exists; however, a limited number are used universally due to drawbacks like radiation exposure, lack of standardization, and difficulties interpreting data. In recent years, several new methods such as the 3D-Transit system and magnetic resonance imaging assessments on small bowel and colonic motility have emerged, with the advantages that they are less invasive, use no radiation, and provide much more detailed information. PURPOSE: This review outlines well-established and emerging methods to evaluate small bowel and colonic motility in clinical settings and in research. The latter include the 3D-Transit system, magnetic resonance imaging assessments, and high-resolution manometry. Procedures, indications, and the relative strengths and weaknesses of each method are summarized.

Three-year follow-up of sacral nerve stimulation for patients with diarrhoea-predominant and mixed irritable bowel syndrome.

AIM: Our unit has recently shown that sacral nerve stimulation (SNS) has a significantly positive short-term effect on selected patients with diarrhoea-predominant or mixed irritable bowel syndrome (IBS). The aim of the present prospective study was to evaluate the medium-term efficacy of SNS for IBS to establish whether SNS could have a future role in the treatment of IBS. METHOD: Patients with IBS who had previously been implanted with a permanent neurostimulator as part of a randomized, controlled, crossover study, were assessed for medium-term follow-up. The primary end-point was change in the IBS-specific symptom score (Gastrointestinal Symptom Rating Scale-Irritable Bowel Syndrome version questionnaire) from baseline to 3-year follow-up. The secondary end-point was a change in the IBS-specific quality of life score (Irritable Bowel Syndrome-Impact Scale questionnaire) from baseline to 3-year follow-up. RESULTS: Of 26 patients, 20 were eligible for 3-year follow-up. The median IBS-specific symptom score was significantly lower at 3-year follow-up (30, range 13-71) than at baseline (62, 45-80) (P = 0.0001). The effect was observed in all symptom clusters within the score. Also, the median IBS-specific quality of life score was significantly improved at 3-year follow-up (52, 26-169) compared with baseline (135, 82-180, P = 0.0002). The effect was observed in all domains of the score. As per the protocol, 75% of patients were judged therapeutic successes. Seventy per cent of patients had a more than 50% reduction in daily IBS symptoms. CONCLUSION: At medium-term follow-up, SNS continues to be an effective treatment for highly selected patients with diarrhoea-predominant or mixed IBS.

Increased yield pressure in the anal canal during sacral nerve stimulation: a pilot study with the functional lumen imaging probe.

BACKGROUND: Sacral nerve stimulation (SNS) is a well-established treatment for fecal incontinence but its mode of action remains obscure. Anal sphincter function is usually evaluated with manometry but resistance to distension may be a more appropriate parameter than luminal pressure. The functional lumen imaging probe allows detailed description of distension properties of the anal canal. Our objective in this study was to characterize the impact of SNS on distension properties of the anal canal in patients with idiopathic fecal incontinence. METHODS: We studied 10 women (median age 64 [44-79] years) with idiopathic fecal incontinence at baseline and during SNS. The luminal geometry of the anal canal was examined with the FLIP at rest and during squeeze and the distensibility of the anal canal was investigated during filling of the bag. KEY RESULTS: All patients were successfully treated with SNS and the mean Wexner Incontinence Score was reduced from 14.9 ± 4 to 7.1 ± 4.8 (P<.001). The pressure required to open the narrowest point of the anal canal during distension (yield pressure) increased from 14.5 ± 12.2 mmHg at baseline to 20.5 ± 13.3 mmHg during SNS (P<.01). The pressure-strain elastic modulus increased non-significantly from 2.2 ± 0.5 to 2.9 ± 1.6 kPa, indicating increased stiffness of the anal canal. CONCLUSION AND INFERENCES: The yield pressure and the resistance to distension increased in response to SNS for idiopathic fecal incontinence. This will inevitably increase the resistance to flow through the anal canal, which may contribute to the benefits of sacral nerve stimulation.

Chronic abdominal pain in long-term spinal cord injury: a follow-up study.

STUDY DESIGN: A longitudinal postal survey. OBJECTIVES: To evaluate the prevalence and characteristics of abdominal pain in long-term spinal cord injury (SCI). SETTING: Members of the Danish SCI Association. METHODS: In 2006, a questionnaire on chronic abdominal pain and discomfort was sent to the 284 members of the Danish SCI association who had been members for at least 10 years; 203 of them responded. An almost identical questionnaire including questions on intensity and interference of pain within the past 7 days, as well as descriptors and treatment, was sent to the 178 surviving members in 2015. RESULTS: Of 130 (73%) responders, 125 answered the question on chronic abdominal pain. The mean time since injury was 30.5 (9.8) years. Chronic abdominal pain or discomfort was reported by 32.8% (41/125), and 23% (29/125) of responders had been at least moderately bothered by this in the past week. Abdominal pain or discomfort was more common in women and in those with self-reported constipation. The median intensity (numeric rating scale) was 6.0 (range 3-10) and it was often associated with autonomic symptoms. Nine (8%) of the 115 individuals who responded in both 2006 and 2015 had developed new abdominal pain or discomfort, 30 (26%) no longer reported it, and 28 (24%) reported it at both time points with a similar intensity. CONCLUSIONS: Chronic abdominal pain or discomfort is common and bothersome in long-term SCI. It has a late onset, but the prevalence and severity do not seem to further increase between 20 and 30 years following SCI.

Does Sacral Nerve Stimulation Improve Continence Through Enhanced Sensitivity of the Anal Canal? A Pilot Study.

BACKGROUND: It has been suggested that the effects of sacral nerve stimulation against fecal incontinence involve neuromodulation at spinal or supraspinal levels. OBJECTIVE: This study aims to investigate the afferent sensory pathways from the anorectum before and during sacral nerve stimulation. DESIGN: This is an explorative study. PATIENTS: Fifteen women with idiopathic fecal incontinence (mean age, 58 ± 12.2 years) were selected. INTERVENTIONS: Cortical evoked potentials were recorded during repeated rapid balloon distension of the rectum and the anal canal both before and during temporary sacral nerve stimulation. Stimuli applied were individualized according to the subjective urge to defecate. MAIN OUTCOME MEASURES: The main outcomes measured were 1) stimulus intensity, 2) latencies and amplitudes of cortical evoked potentials, and 3) spectral content in predefined frequency bands of cortical evoked potentials. RESULTS: The median Wexner fecal incontinence score improved from 15.5 ± 3.6 before to 6.7 ± 5 during sacral nerve stimulation (p < 0.001). Sacral nerve stimulation did not affect the threshold for urge to defecate during rectal distension (p = 0.64) but reduced the threshold from stimulation of the anal canal by 50% (p = 0.03). No statistically significant differences were found in latencies, amplitudes, or spectral analysis. LIMITATIONS: This is a pilot study of limited size. CONCLUSIONS: In patients with idiopathic fecal incontinence, sacral nerve stimulation reduced the threshold for urge to defecate elicited from the anal canal, whereas supraspinal responses remained unaltered. This may suggest that sacral nerve stimulation, at least in part, acts via somatic afferent fibers enhancing anal sensation.

Pelvic floor electrophysiology in spinal cord injury.

OBJECTIVE: The study aimed to investigate sacral peripheral nerve function and continuity of pudendal nerve in patients with chronic spinal cord injury (SCI) using pelvic floor electrophysiological tests. METHODS: Twelve patients with low cervical or thoracic SCI were prospectively included. Quantitative external anal sphincter (EAS) muscle electromyography (EMG), pudendal nerve terminal motor latency (PNTML) testing, bulbocavernosus reflex (BCR) testing and pudendal short-latency somatosensory-evoked potential (SEP) measurement were performed. RESULTS: In EAS muscle EMG, two patients had abnormal increased spontaneous activity and seven prolonged motor unit potential duration. PNTML was normal in 10 patients. BCR was present with normal latency in 11 patients and with prolonged latency in one. The second component of BCR could be recorded in four patients. SEPs showed absent cortical responses in 11 patients and normal latency in one. CONCLUSIONS: Pudendal nerve and sacral lower motor neuron involvement are significantly associated with chronic SCI, most prominently in EAS muscle EMG. The frequent finding of normal PNTML latencies supports earlier concerns on the utility of this test; however, BCR and pudendal SEPs may have clinical relevance. SIGNIFICANCE: As intact peripheral nerves including pudendal nerve are essential for efficient supportive therapies, pelvic floor electrophysiological testing prior to these interventions is highly recommended.