High-Affinity-Mediated Viral Entry Triggers Innate Affinity Escape Resulting in Type I IFN Resistance and Impaired T Cell Immunity.

Increased receptor binding affinity may allow viruses to escape from Ab-mediated inhibition. However, how high-affinity receptor binding affects innate immune escape and T cell function is poorly understood. In this study, we used the lymphocytic choriomeningitis virus (LCMV) murine infection model system to create a mutated LCMV exhibiting higher affinity for the entry receptor α-dystroglycan (LCMV-GPH155Y). We show that high-affinity receptor binding results in increased viral entry, which is associated with type I IFN (IFN-I) resistance, whereas initial innate immune activation was not impaired during high-affinity virus infection in mice. Consequently, IFN-I resistance led to defective antiviral T cell immunity, reduced type II IFN, and prolonged viral replication in this murine model system. Taken together, we show that high-affinity receptor binding of viruses can trigger innate affinity escape including resistance to IFN-I resulting in prolonged viral replication.

Investigating the impact of a chronic disease self-management programme on depression and quality of life scores in an Irish sample.

Depression is more common among people with chronic conditions than in the general population and can negatively influence both health behaviours and outcomes. The Chronic Disease Self-Management Programme (CDSMP) is a six-week psycho-educational programme designed to promote self-efficacy and to teach patients skills for managing their chronic conditions. A longitudinal design evaluated the effect of the CDSMP on depression in an Irish cohort. Self-report data on psychological wellbeing were collected at baseline (n = 263), immediately post-program (n = 102), and six months (n = 81) after enrolment. CDSMP participation was associated with a significant decrease in the mean depression score of the whole sample, across the three time points. Significant improvements in quality of life and health interference in social activities were also observed among those who met criteria for depression on the PHQ-8 at baseline, but not their peers with sub-threshold depression scores. Quality of life continued to improve between the end of the programme and 6-month follow-up. These findings support the efficacy of the CDSMP in the treatment of chronic conditions, as well as its role in promoting sustainable changes to quality of life.

Goal commitment is supported by vmPFC through selective attention.

When striking a balance between commitment to a goal and flexibility in the face of better options, people often demonstrate strong goal perseveration. Here, using functional MRI (n = 30) and lesion patient (n = 26) studies, we argue that the ventromedial prefrontal cortex (vmPFC) drives goal commitment linked to changes in goal-directed selective attention. Participants performed an incremental goal pursuit task involving sequential decisions between persisting with a goal versus abandoning progress for better alternative options. Individuals with stronger goal perseveration showed higher goal-directed attention in an interleaved attention task. Increasing goal-directed attention also affected abandonment decisions: while pursuing a goal, people lost their sensitivity to valuable alternative goals while remaining more sensitive to changes in the current goal. In a healthy population, individual differences in both commitment biases and goal-oriented attention were predicted by baseline goal-related activity in the vmPFC. Among lesion patients, vmPFC damage reduced goal commitment, leading to a performance benefit.

Acute monoarticular hip joint pseudogout masquerading as septic arthritis.

Monoarticular pseudogout of the hip joint is rare and to the best of our knowledge only four other cases exist in the literature. We present a case of primary monoarticular pseudogout affecting the right hip in a patient in his 50s. The diagnosis was confirmed through ultrasound-guided synovial fluid aspiration and crystal analysis. The patient was treated conservatively with analgesia and after hip joint aspiration resulted in dramatic symptomatic resolution. Acute attack of pseudogout is a rare cause of acute hip pain. The clinical features may mimic hip joint septic arthritis and should be considered in the differential diagnosis of any presentation of acute joint pain. Diagnosis is important to avoid unnecessary medical and surgical intervention reducing hospital stay.

Consensus for the Treatment of Tinea Pedis: A Systematic Review of Randomised Controlled Trials.

Objective: To systematically review literature enabling the comparison of the efficacy of pharmaceutical treatments for tinea pedis in adults. Design: Systematic review of randomised controlled trials (RCTs) with mycological cure as the primary outcome. Secondary outcomes did include the clinical assessment of resolving infection or symptoms, duration of treatment, adverse events, adherence, and recurrence. Eligibility Criteria: Study participants suffering from only tinea pedis that were treated with a pharmaceutical treatment. The study must have been conducted using an RCT study design and recording age of the participant > 16 years of age. Results: A total of seven studies met the inclusion criteria, involving 1042 participants. The likelihood of resolution in study participants treated with terbinafine was RR 3.9 (95% CI: 2.0−7.8) times those with a placebo. Similarly, the allylamine butenafine was effective by RR 5.3 (95% CI: 1.4−19.6) compared to a placebo. Butenafine was similarly efficacious to terbinafine RR 1.3 (95% CI: 0.4−4.4). Terbinafine was marginally more efficacious than itraconazole, RR 1.3 (95% CI: 1.1−1.5). Summary/Conclusion: Topical terbinafine and butenafine treatments of tinea pedis were more efficacious than placebo. Tableted terbinafine and itraconazole administered orally were efficacious in the drug treatment of tinea pedis fungal infection. We are concerned about how few studies were available that reported the baseline characteristics for each treatment arm and that did not suffer greater than 20% loss to follow-up. We would like to see improved reporting of clinical trials in academic literature. Registration name: Treatment's for athlete's foot­systematic review with meta-analysis [CRD42020162078].

Immunohistochemical confirmation of the presence of smooth muscle in the normal neonatal anorectum and in neonates with anorectal malformations.

AIM: To evaluate the presence of smooth muscle in relation to the anorectum in neonates that are normal and in neonates with anorectal malformations using immunohistochemical staining of antibodies specific to smooth muscle actin (SMA). METHODS: Research ethics committee approval was obtained to study historical neonatal tissue sections. 7-15-µ thickness, sagittal sections of both normal anorectums (NA) and neonates with anorectal malformations (ARM) were available to study. The fragile tissue predates the development of charged glass microscope slides that are inherent to contemporary immunohistochemistry (IHC). Normal appendix sections on non-charged slides were used to establish and optimise a novel, steam generated heat, antigen retrieval protocol. This technique of "gentle" antigen retrieval allows preservation of tissue architecture whilst maintaining adequate staining of tissue on non-charged glass microscope slides. NA and ARM tissue was stained and compared to control NA and ARM sections. RESULTS: SMA staining was observed in sagittal sections of both normal neonatal anorectums and neonates with anorectal malformations, confirming the presence of smooth muscle. CONCLUSION: This preliminary work confirms the presence of smooth muscle in the anorectum of neonates that are normal and in neonates with anorectal malformations. It is likely that the smooth muscle complex demonstrated represents the internal anal sphincter in the normal anorectum. It is postulated that the smooth muscle complex seen in anorectal malformations may represent a similar internal anal sphincter complex which maybe of functional significance. Further IHC of tissue sections will allow reconstruction of the exact three-dimensional smooth muscle structure of the anorectum in neonates that are normal and neonates with anorectal malformations.

Neonatal functional intestinal obstruction and the presence of severely immature ganglion cells on rectal biopsy: 6 year experience.

PURPOSE: We report our experience of managing eight babies who presented with neonatal intestinal obstruction and whose rectal biopsies showed severely immature ganglion cells. METHODS: Neonatal unit records were reviewed to detect patients with suspected Hirschsprung's disease or functional intestinal obstruction. Those with intestinal atresia, anorectal malformation, malrotation, cystic fibrosis and prematurity were excluded. RESULTS: We identified 73 patients born at term. Twenty-seven did not need a rectal biopsy. Twenty-one had biopsy proven Hirschsprung's disease, while 17 had a normal rectal biopsy. Eight patients, all of whom presented with severe abdominal distension, showed immature ganglion cells. Seven had failed to pass meconium after birth. X-rays in all patients showed distended loops of bowel. Two neonates underwent an emergency laparotomy and a stoma. A repeat biopsy at 3 months showed maturation of ganglion cells and the stoma was reversed. Rectal biopsy was repeated in two other patients 2-9 months after the first biopsy and showed mature ganglion cells. At follow-up, one patient still suffers from severe constipation. Seven are asymptomatic now, including the two patients who needed a stoma. CONCLUSION: Immature ganglion cells on rectal biopsy may be an indicator of transient functional immaturity of the intestine.

An analysis of the incidence, causes and preventative approaches to gram-negative bloodstream infections of hepatopancreatobiliary origin.

BACKGROUND: Gram-negative bloodstream infection (GNBSI) is a threat to public health in terms of mortality and antibiotic resistance. The hepatopancreatobiliary (HPB) cohort accounts for 15%-20% of GNBSI, yet few strategies have been explored to reduce HPB GNBSI. AIM: To identify clinical factors contributing to HPB GNBSI and strategies for its prevention. METHODS: We performed a retrospective analysis of 433 cases of HPB GNBSI presenting to four hospitals between April 2015 and May 2019. We extracted key data from hospital and primary care records including: the underlying source of GNBSI; previous documentation of biliary disease; and any previous surgical or non-surgical management. FINDINGS: Out of 433 cases of HPB GNBSI, 388 had clear evidence of HPB origin. The source of GNBSI was related to gallstone disease in 282 of the 388 cases (73%) and to HPB malignancy in 70 cases (18%). Of the gallstone-related cases, 117 had previously been diagnosed with symptomatic gallstones. Of the 117 with a previous presentation, 93 could have been prevented with a laparoscopic cholecystectomy at the first presentation of gallstones, while 18 could have been prevented if intraoperative biliary tract imaging had been performed during a prior cholecystectomy. Of the 70 malignant cases, five could have been prevented through earlier biliary stenting, use of metal stents instead of plastic stents or earlier pancreaticoduodenectomy. DISCUSSION: The incidence of HPB GNBSI could be reduced by up to 30% by the implementation of alternative management strategies in this cohort.

Microglia: sculptors of neuropathic pain?

Neuropathic pain presents a huge societal and individual burden. The limited efficacy of current analgesics, diagnostic markers and clinical trial outcome measures arises from an incomplete understanding of the underlying mechanisms. A large and growing body of evidence has established the important role of microglia in the onset and possible maintenance of neuropathic pain, and these cells may represent an important target for future therapy. Microglial research has further revealed their important role in structural remodelling of the nervous system. In this review, we aim to explore the evidence for microglia in sculpting nervous system structure and function, as well as their important role in neuropathic pain, and finally integrate these studies to synthesize a new model for microglia in somatosensory circuit remodelling, composed of six key and inter-related mechanisms. Summarizing the mechanisms through which microglia modulate nervous system structure and function helps to frame a better understanding of neuropathic pain, and provide a clear roadmap for future research.

Nutritional and metabolic issues in solid organ transplantation: targets for future research.

Cardiovascular morbidity and mortality complicates the course of a significant proportion of renal transplant recipients and is increasingly prevalent among recipients of other solid organ transplants, such as heart or liver transplant patients. A posttransplant metabolic syndrome comprised of hypertension, dyslipidemia, increased fat mass/obesity, and glucose intolerance, combined with other metabolic side effects derived from glucocorticoid and calcineurin inhibitor immunosuppression, attenuates allograft and patient survival. After the early posttransplant years, infection and rejection are the major risks that recipients face, whereas metabolic and cardiovascular disease become the most serious long term risk factors impacting patient survival. While significant advances in immunosuppressive therapy have prolonged the allograft and patient survival in solid organ transplant recipients, little has been done in the way of controlled interventional trials utilizing nutritional, dietary, or biobehavioral modification, especially when combined with drug treatment to reduce the effects of the posttransplant metabolic syndrome. In addition to cardiovascular morbidity, metabolic bone disease, osteopenia, and impaired growth in children pose significant challenges in posttransplant management. In this review, the data from some of the known observational dietary trials in solid organ transplant recipients and prior evidence obtained from studies in chronic kidney disease and the general population is considered in formulating new targets for future research to deal with this ever-increasing population of high risk patients.

Chromogranin A polymorphisms are associated with hypertensive renal disease.

Chromogranin A is released together with epinephrine and norepinephrine from catecholaminergic cells. Specific endopeptidases cleave chromogranin A into biologically active peptide fragments, including catestatin, which inhibits catecholamine release. Previous studies have suggested that a deficit in this sympathetic "braking" system might be an early event in the pathogenesis of human hypertension. Whether chromogranin A (CHGA) polymorphisms predict end-organ complications of hypertension, such as end-stage renal disease, is unknown. Among blacks, we studied common genetic variants spanning the CHGA locus in 2 independent case-control studies of hypertensive ESRD. Two haplotypes were significantly more frequent among subjects with hypertensive ESRD: 1) in the promoter (5') region, G-462A-->T-415C-->C-89A, haplotype ATC (adjusted odds ratio = 2.65; P = 0.037), and 2) at the 3'-end, C11825T (3'-UTR, C+87T)-->G12602C, haplotype TC (adjusted odds ratio = 2.73, P = 0.0196). Circulating levels of catestatin were lower among those with hypertensive ESRD than controls, an unexpected finding given that peptide levels are usually elevated in ESRD because of reduced renal elimination. We found that the 3'-UTR + 87T variant decreased reporter gene expression, providing a possible mechanistic explanation for diminished catestatin. In summary, common variants in chromogranin A associate with the risk of hypertensive ESRD in blacks.

Predictive validity of a medication adherence measure in an outpatient setting.

This study examines the psychometric properties and tests the concurrent and predictive validity of a structured, self-reported medication adherence measure in patients with hypertension. The authors also assessed various psychosocial determinants of adherence, such as knowledge, social support, satisfaction with care, and complexity of the medical regimen. A total of 1367 patients participated in the study; mean age was 52.5 years, 40.8% were male, 76.5% were black, 50.8% graduated from high school, 26% were married, and 54.1% had income <$5,000. The 8-item medication adherence scale was reliable (alpha=.83) and significantly associated with blood pressure control (P<.05). Using a cutpoint of <6, the sensitivity of the measure to identify patients with poor blood pressure control was estimated to be 93%, and the specificity was 53%. The medication adherence measure proved to be reliable, with good concurrent and predictive validity in primarily low-income, minority patients with hypertension and might function as a screening tool in outpatient settings with other patient groups.

Cardiovascular outcomes in high-risk hypertensive patients stratified by baseline glomerular filtration rate.

BACKGROUND: Chronic kidney disease is common in older patients with hypertension. OBJECTIVE: To compare rates of coronary heart disease (CHD) and end-stage renal disease (ESRD) events; to determine whether glomerular filtration rate (GFR) independently predicts risk for CHD; and to report the efficacy of first-step treatment with a calcium-channel blocker (amlodipine) or an angiotensin-converting enzyme inhibitor (lisinopril), each compared with a diuretic (chlorthalidone), in modifying cardiovascular disease (CVD) outcomes in high-risk patients with hypertension stratified by GFR. DESIGN: Post hoc subgroup analysis. SETTING: Multicenter randomized, double-blind, controlled trial. PARTICIPANTS: Persons with hypertension who were 55 years of age or older with 1 or more risk factors for CHD and who were stratified into 3 baseline GFR groups: normal or increased (> or = 90 mL/min per 1.73 m2; n = 8126 patients), mild reduction (60 to 89 mL/min per 1.73 m2; n = 18,109 patients), and moderate or severe reduction (< 60 mL/min per 1.73 m2; n = 5662 patients). INTERVENTIONS: Random assignment to chlorthalidone, amlodipine, or lisinopril. MEASUREMENTS: Rates of ESRD, CHD, stroke, and combined CVD (CHD, coronary revascularization, angina, stroke, heart failure, and peripheral arterial disease). RESULTS: In participants with a moderate to severe reduction in GFR, 6-year rates were higher for CHD than for ESRD (15.4% vs. 6.0%, respectively). A baseline GFR of less than 53 mL/min per 1.73 m2 (compared with >104 mL/min per 1.73 m2) was independently associated with a 32% higher risk for CHD. Amlodipine was similar to chlorthalidone in reducing CHD (16.0% vs. 15.2%, respectively; hazard ratio, 1.06 [95% CI, 0.89 to 1.27]), stroke, and combined CVD (CHD, coronary revascularization, angina, stroke, heart failure, and peripheral arterial disease), but less effective in preventing heart failure. Lisinopril was similar to chlorthalidone in preventing CHD (15.1% vs. 15.2%, respectively; hazard ratio, 1.00 [CI, 0.84 to 1.20]), but was less effective in reducing stroke, combined CVD events, and heart failure. LIMITATIONS: Proteinuria data were not available, and combination therapies were not tested. CONCLUSIONS: Older high-risk patients with hypertension and reduced GFR are more likely to develop CHD than to develop ESRD. A low GFR independently predicts increased risk for CHD. Neither amlodipine nor lisinopril is superior to chlorthalidone in preventing CHD, stroke, or combined CVD, and chlorthalidone is superior to both for preventing heart failure, independent of level of renal function.

Renal outcomes in high-risk hypertensive patients treated with an angiotensin-converting enzyme inhibitor or a calcium channel blocker vs a diuretic: a report from the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT).

BACKGROUND: This study was performed to determine whether, in high-risk hypertensive patients with a reduced glomerular filtration rate (GFR), treatment with a calcium channel blocker or an angiotensin-converting enzyme inhibitor lowers the incidence of renal disease outcomes compared with treatment with a diuretic. METHODS: We conducted post hoc analyses of the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). Hypertensive participants 55 years or older with at least 1 other coronary heart disease risk factor were randomized to receive chlorthalidone, amlodipine, or lisinopril for a mean of 4.9 years. Renal outcomes were incidence of end-stage renal disease (ESRD) and/or a decrement in GFR of 50% or more from baseline. Baseline GFR, estimated by the simplified Modification of Diet in Renal Disease equation, was stratified into normal or increased (> or =90 mL /min per 1.73 m(2), n = 8126), mild reduction (60-89 mL /min per 1.73 m(2), n = 18 109), or moderate-severe reduction (<60 mL /min per 1.73 m(2), n = 5662) in GFR. Each stratum was analyzed for effects of the treatments on outcomes. RESULTS: In 448 participants, ESRD developed. Compared with patients taking chlorthalidone, no significant differences occurred in the incidence of ESRD in patients taking amlodipine in the mild (relative risk [RR], 1.47; 95% confidence interval [CI], 0.97-2.23) or moderate-severe (RR, 0.92; 95% CI, 0.68-1.24) reduction in GFR groups. Compared with patients taking chlorthalidone, no significant differences occurred in the incidence of ESRD in patients taking lisinopril in the mild (RR, 1.34; 95% CI, 0.87-2.06) or moderate-severe (RR, 0.98; 95% CI, 0.73-1.31) reduction in GFR groups. In patients with mild and moderate-severe reduction in GFR, the incidence of ESRD or 50% or greater decrement in GFR was not significantly different in patients treated with chlorthalidone compared with those treated with amlodipine (odds ratios, 0.96 [P = .74] and 0.85 [P = .23], respectively) and lisinopril (odds ratios, 1.13 [P = .31] and 1.00 [P = .98], respectively). No difference in treatment effects occurred for either end point for patients taking amlodipine or lisinopril compared with those taking chlorthalidone across the 3 GFR subgroups, either for the total group or for participants with diabetes at baseline. At 4 years of follow-up, estimated GFR was 3 to 6 mL /min per 1.73 m(2) higher in patients assigned to receive amlodipine compared with chlorthalidone, depending on baseline GFR stratum. CONCLUSIONS: In hypertensive patients with reduced GFR, neither amlodipine nor lisinopril was superior to chlorthalidone in reducing the rate of development of ESRD or a 50% or greater decrement in GFR. Participants assigned to receive amlodipine had a higher GFR than those assigned to receive chlorthalidone, but rates of development of ESRD were not different between the groups.

Outcomes of full-term infants with bilious vomiting: observational study of a retrieved cohort.

UNLABELLED: Bilious vomiting in a neonate may be a sign of intestinal obstruction often resulting in transfer requests to surgical centres. The aim of this study was to assess the use of clinical findings at referral in predicting outcomes and to determine how often such patients have a time-critical surgical condition (eg, volvulus, where a delay in treatment is likely to compromise gut viability). METHODS: 4-year data and outcomes of all term newborns aged ≤7 days with bilious vomiting transferred by a regional transfer service were analysed. Specificity, sensitivity, likelihood ratios, correlations, prior and posterior probability of clinical findings in predicting newborns with surgical diagnosis were calculated. RESULTS: Of 163 neonates with bilious vomiting, 75 (46%) had a surgical diagnosis and 23 (14.1%) had a time-critical surgical condition. The diagnosis of a surgical condition in neonates with bilious vomiting was significantly associated with abdominal distension (χ(2)=5.17, p=0.023), abdominal tenderness (χ(2)=5.90, p=0.015) and abnormal abdominal X-ray findings (χ(2)=5.68, p=0.017) but not with palpation findings of a soft as compared with a tense abdomen (χ(2)=3.21, p=0.073). Abnormal abdominal X-ray, abdominal distension and tenderness had 97%, 74% and 62% sensitivity, respectively, with regard to association with an underlying surgical diagnosis. Normal abdominal X-ray reduced the posterior probability of surgical diagnosis from 50% to 16%. Overall, clinical findings at referral did not differentiate between infants with or without surgical or time-critical condition. CONCLUSIONS: We recommend that term neonates with bilious vomiting referred for transfer are prioritised as time critical.

Pathophysiology of chronic childhood constipation: functional and morphological evaluation by anorectal manometry and endosonography and colonic transit study.

BACKGROUND: Chronic idiopathic constipation (IC) is a common problem in children. We hypothesised that hypertonicity and overactivity of the internal anal sphincter (IAS) contributed to childhood IC. METHOD: This was a prospective study of children who were admitted for investigation and treatment of chronic constipation at the gastrointestinal motility clinic in Guy's and St. Thomas' Hospital, NHS Foundation Trust, London. All children had a colonic transit marker study followed by anorectal manometry and anal endosonography under ketamine anesthesia. We used a validated symptom severity (SS) score questionnaire for assessment of constipation and fecal incontinence on admission to hospital and during follow-up for 12months. The SS score of 0 was the best and 65 the worst. RESULTS: Of 92 children, 57 were male and median (range) age was 8.46years (3.35-14.97). Duration of symptoms was 4.7years (0.3-13). Soiling was present in 88 (96%) patients, delay in defecation of once every 2 to 3days or less frequently in 86 (93%) and a palpable fecaloma (megarectum) on abdominal examination in 76 (83%). 42 children had 'fecal impaction' requiring disimpaction of stool from the rectum under general anesthesia and 50 had 'no impaction'. The median IAS resting pressure was within the normal range measuring 55mm Hg (25-107) and median amplitude and frequency of the IAS contractions were 10mm Hg (2.0-58) and 17cycles per min (5.0-34), respectively. The median IAS thickness was 0.93mm (0.5-2.0). There was no correlation between amplitude and frequency of anorectal contractions and anal sphincter resting pressure. The mean right colonic transit time was 8.55 (standard deviation ±13.22) h, left colonic transit time was 11.51h (±13.21), rectosigmoid transit time was 25.91h (±18.89) and total colonic transit time was 45.97h (±17.69). CONCLUSION: The anal sphincter resting pressure is normal in children with chronic IC. Increased frequency and amplitude of IAS contractions seen in these patients do not cause raised anal sphincter resting pressure or obstructive defecation. Further studies should be done to investigate the role of external anal sphincter dysfunction in pathophysiology of childhood constipation and fecal incontinence.

Dynamic MRI (dMRI) as a guide to therapy in children and adolescents with persistent full thickness rectal prolapse: a single centre review.

INTRODUCTION: Full thickness rectal prolapse (FTRP) tends to be self-limiting in children and is usually managed expectantly. However, it may persist and therefore requires surgical correction. There is no consensus upon operative management, and no one procedure has uniformly good outcomes. The aim of this study was to determine whether pre-operative diagnostic dMRI findings might help identify the operative approach best suited to the anatomical abnormality of the individual child. METHODS: A retrospective review of ten children with persistent FTRP who had been evaluated pre-operatively with dMRI between 2002 and 2010 was performed. In this preliminary work, MRI findings were not used to direct surgical management. Data collected included: age at presentation, underlying medical conditions, timing and findings of dMRI (specifically, descent of rectum from pubococcygeal (PC) line on straining), timing and type of surgery, surgical outcomes, and length of follow-up. RESULTS: Ten children (two female) with a median age of 11 years 2 months (range 8-15 years) with FTRP refractory to conservative treatment underwent diagnostic pre-operative dMRI. Median perineal descent from PC line on straining during dMRI was 3.5 cm (range 1-4 cm). Three of the seven children with severe descent initially underwent a Delorme's procedure, and all required surgical revision. Five with severe descent and one with moderate descent achieved a cure following rectopexy. Two patients with mild descent underwent a Delorme's procedure. One achieved a cure, and the other developed recurrence. Of the ten patients, seven had no prolapse at the last clinic review, and three have persisting symptoms. Median follow-up was 3.5 years (range 1-6). CONCLUSION: The findings from this small study favour rectal suspension techniques for surgical management of moderate to severe perineal descent on dMRI. Delorme's procedure should only be applied to those with mild descent. Pre-operative dMRI assessment may have a potential role in guiding surgical intervention for children. However, future prospective studies will be required to confirm this assertion.

Transcutaneous needle-free injection of botulinum toxin: a novel treatment of childhood constipation and anal fissure.

PURPOSE: Constipation is a common problem in children, and when it becomes chronic fecal impaction, overflow soiling and megarectum may develop. Children with chronic idiopathic constipation (IC) may not respond to conventional treatments of laxatives, enemas, and toilet training. The aims of the study were to evaluate the long-term outcome of transcutaneous needle-free injection of botulinum toxin (TNFBT) into the external anal sphincter (EAS) and to assess the extent of the toxin penetration into the sphincter. METHOD: Children were recruited if symptomatic with chronic constipation, soiling, painful defecation, and withholding behavior requiring disimpaction of stool and rectal biopsy under general anesthesia. A total dose of 200 U of botulinum toxin (BT) (Dysport; Ipsen Limited, Slough, United Kingdom) was injected transcutaneously into the EAS at 3 and 9-o'clock positions using J-tip needle-free syringes (National Medical Products Inc, Irvine, Calif). The depth and width of toxin penetration was assessed by endosonography. Outcome was measured by a validated symptom severity (SS) score questionnaire. The total SS score ranged between 0 (best) and 65 (worst). The outcome was compared with 31 children in a comparable historical control group at 3 and 12-month follow-up. RESULTS: Sixteen children were recruited with median age of 6.11 (range, 3-14.85) years and median duration of symptoms of 3.9 years (1.6-11.5). On endosonography, the median depth and width of BT penetration was 8 (7-10) mm and 8 (6-10) mm, respectively. At 3-month follow-up, the median SS score improved in all children after TNFBT from 32.50 (5-57) to 7.50 (0-26) (Wilcoxon's P < .0001). There were significant improvements in symptoms of constipation, soiling, painful defecation, general health and behavior, and fecal impaction of rectum (P < .05). Anal fissures healed in all 4 children. The SS score in the control group improved from 33 (12-49) to 15 (0-40) (P < .0001). At 12-month follow-up, the improvement of SS score in TNFBT group was significantly more than the control group as follows: 4 (0-25) vs 15 (0-51), respectively (Mann-Whitney U P < .002). Three patients had a second TNFBT injection for relapsed symptoms. There were no complications. The transcutaneous needle-free injection of botulinum toxin eliminates the risk of intravascular injection or needlestick injury. The transcutaneous needle-free injection of botulinum toxin also has other therapeutic applications including an alternative therapy to biofeedback training for dyssynergia of the EAS, treatment of muscle limb spasticity in cerebral palsy, and cosmetic treatment of overactive facial muscles and wrinkles and hyperhydrosis. CONCLUSION: Transcutaneous needle-free injection of botulinum toxin into the external anal sphincter is a novel and safe new treatment of chronic idiopathic constipation and anal fissure in children. A second injection may be required in 20% of patients.

Antegrade continence enema (ACE): current practice.

The purpose of this study was to assess current status of antegrade continence enema (ACE) procedure taking into account the recent improvement in the technique and outcome. Reviewing our record of 48 patients with ACE procedure performed between January 2002 and May 2007, we found that the underlying diagnoses were idiopathic constipation in 56%, anorectal malformation in 31%, spina bifida in 8% and Hirschsprung's disease in 4%. Mean age of operation was 10.7 years. Appendix was used as stoma in 73% of cases. Stomal stenosis requiring revision was seen in 6% of cases and continence was achieved in 92% of cases. A systematic search of database was performed for the same period. Twenty-four studies describing 676 patients were found. The mean age was 10 years and various sites used for ACE were, right side of abdomen in 71%, umbilicus in 15% and left side of abdomen in 14%. The incidence of open and laparoscopic procedures were 87 and 13%, respectively. Appendix was used for stoma in 76% procedures. Other operative modalities were retubularised colon, retubularised ileum, caecal button and caecostomy tube, etc. The mean volume of enema fluid used was 516 ml. The mean evacuation time was 42 min. Stomal stenosis requiring revision was seen in 13% of cases. Continence was achieved in 93% of cases. There has been significant improvement in the outcome during last 5 years in comparison to the outcome published in late 1990s. Advancements in techniques, better-trained stoma care nurses and better stoma appliances could have played major role in this success.