Ontogeny of human IgE-expressing B cells and plasma cells.

BACKGROUND: IgE-expressing (IgE+ ) plasma cells (PCs) provide a continuous source of allergen-specific IgE that is central to allergic responses. The extreme sparsity of IgE+ cells in vivo has confined their study almost entirely to mouse models. OBJECTIVE: To characterize the development pathway of human IgE+ PCs and to determine the ontogeny of human IgE+ PCs. METHODS: To generate human IgE+ cells, we cultured tonsil B cells with IL-4 and anti-CD40. Using FACS and RT-PCR, we examined the phenotype of generated IgE+ cells, the capacity of tonsil B-cell subsets to generate IgE+ PCs and the class switching pathways involved. RESULTS: We have identified three phenotypic stages of IgE+ PC development pathway, namely (i) IgE+ germinal centre (GC)-like B cells, (ii) IgE+ PC-like 'plasmablasts' and (iii) IgE+ PCs. The same phenotypic stages were also observed for IgG1+ cells. Total tonsil B cells give rise to IgE+ PCs by direct and sequential switching, whereas the isolated GC B-cell fraction, the main source of IgE+ PCs, generates IgE+ PCs by sequential switching. PC differentiation of IgE+ cells is accompanied by the down-regulation of surface expression of the short form of membrane IgE (mIgES ), which is homologous to mouse mIgE, and the up-regulation of the long form of mIgE (mIgEL ), which is associated with an enhanced B-cell survival and expressed in humans, but not in mice. CONCLUSION: Generation of IgE+ PCs from tonsil GC B cells occurs mainly via sequential switching from IgG. The mIgEL /mIgES ratio may be implicated in survival of IgE+ B cells during PC differentiation and allergic disease.

Urinary incontinence persisting after childbirth: extent, delivery history, and effects in a 12-year longitudinal cohort study.

OBJECTIVE: To investigate the extent of persistent urinary incontinence (UI) 12 years after birth, and association with delivery-mode history and other factors. DESIGN: Twelve-year longitudinal cohort study. SETTING: Maternity units in Aberdeen, Birmingham, and Dunedin. POPULATION: Women who returned questionnaires 3 months and 12 years after index birth. METHODS: Data on all births over a period of 12 months were obtained from the units and then women were contacted by post. MAIN OUTCOME MEASURE: Persistent UI reported at 12 years, with one or more previous contact. RESULTS: Of 7879 women recruited at 3 months, 3763 (48%) responded at 12 years, with 2944 also having responded at 6 years; non-responders had similar obstetric characteristics. The prevalence of persistent UI was 37.9% (1429/3763). Among those who had reported UI at 3 months, 76.4% reported it at 12 years. Women with persistent UI had lower SF12 quality of life scores. Compared with having only spontaneous vaginal deliveries (SVDs), women who delivered exclusively by caesarean section were less likely to have persistent UI (odds ratio, OR 0.42, 95% CI 0.33-0.54). This was not the case in women who had a combination of caesarean section and SVD births (OR 1.01, 95% CI 0.78-1.30). Older age at first birth, greater parity, and overweight/obesity were associated with persistent UI. Of 54 index primiparae with UI before pregnancy, 46 (85.2%) had persistent UI. CONCLUSIONS: This study, demonstrating that UI persists to 12 years in about three-quarters of women, and that risk was only reduced with caesarean section if women had no other delivery mode, has practice implications. TWEETABLE ABSTRACT: A longitudinal study of 3763 women showed a prevalence of persistent UI 12 years after birth of 37.9%.

Intrinsic properties of germinal center-derived B cells promote their enhanced class switching to IgE.

BACKGROUND: Research on the origins and development of human IgE-expressing (IgE(+) ) cells is required for understanding the pathogenesis of allergy and asthma. These studies have been thwarted by the rarity of IgE(+) cells in vivo and the low frequency of class switch recombination (CSR) to IgE ex vivo. To determine the main source of IgE(+) cells, we investigated the relation between the phenotypic composition of tonsil B cells and the CSR to IgE ex vivo. METHODS: Human tonsil B cells were analyzed by flow cytometry (FACS) and cultured with IL-4 and anti-CD40 to induce CSR to IgE. Naïve, germinal center (GC), early GC (eGC), and memory tonsil B cells were isolated by FACS, and their capacities for IL-4 and anti-CD40 signaling, cell proliferation, and de novo class switching to IgE were analyzed by RT-PCR and FACS. RESULTS: B cells from different tonsils exhibited varying capacities for CSR to IgE ex vivo. This was correlated with the percentage of eGC B cells in the tonsil at the outset of the culture. Despite relatively poor cell viability, eGC and GC B-cell cultures produced the highest yields of IgE(+) cells compared to naïve and memory B-cell cultures. The main factors accounting for this result were the strength of IL-4R and CD40 signaling and relative rates of cell proliferation. CONCLUSIONS: This study shows that the maturation state of tonsil B cells determines their capacity to undergo class switching to IgE ex vivo, with the GC-derived B cells yielding the highest percentage of IgE(+) cells.

Effect of anticholinergics on the overactive bladder and bowel domain of the electronic personal assessment questionnaire (ePAQ).

INTRODUCTION AND HYPOTHESIS: Evidence suggests that OAB (overactive bladder) can occur alongside disorders of the colon, such as irritable bowel syndrome (IBS). Moreover, patients with constipation are more likely to develop OAB symptoms than those without. Anticholinergic medications (AcH) are commonly used for treating OAB, and can result in the unwanted side effects of constipation. We aimed to study the relationship of AcH, and their effects on quality of life using the electronic Personal Assessment Questionnaire (ePAQ) by assessing changes in the bowel and bladder domains, pre- and post-AcH treatment. METHODS: Ninety patients completed the ePAQ pre- and post-AcH treatment from January 2011 to April 2014. Data were collected retrospectively and prospectively, and analysed using a paired t test. Effect size (ES) was calculated for OAB and bowel domains to quantify the effect on QoL. RESULTS: There was a significant improvement in the OAB (p = 0.0005) and bowel domains (p = 0.0005). In the bowel domains, the largest effect size was seen for IBS (0.5) followed by continence (0.4), evacuation (0.375) and a small ES was seen for constipation (0.2). There was a reduction in the "degree of bother" in OAB and bowel domains. CONCLUSIONS: Patients may benefit from the possible effects of AcH on their bowels, and assessment of all aspects of pelvic floor function is important before commencing AcH. This may help to counsel patients, with possibly improved compliance with therapy.

Bladder exstrophy combined with uterovaginal prolapse and its surgical management: case report and literature review.

We describe a case of a postmenopausal woman with a corrected bladder exstrophy (BE) who presented with a uterovaginal prolapse complicated by calcified fibroids and discuss its surgical management. A 51-year-old woman presented with a uterovaginal prolapse. She had previously had one full term delivery by caesarean section 20 years ago. She had an ileal conduit performed for her BE at birth. A computed tomography scan revealed significant pelvic anomaly and the uterus contained multiple calcified fibroids. Due to the complexity of her condition the surgical management was planned in two stages: initial examination under anaesthetic in conjunction with a consultant urologist and then the definitive planned reconstructive surgery. This case describes the need for careful evaluation and planning of complex surgery and the successful surgical management option for correction of uterovaginal prolapse in patients with BE. A vaginal approach seemed to be a most sensible route to correct the prolapse in view of her previous multiple abdominal surgeries.

Bladder perforation during sling procedures: diagnosis and management of injury.

INTRODUCTION AND HYPOTHESIS: Midurethral slings are an effective and minimally invasive treatment for stress urinary incontinence. One of the most common intraoperative complications is bladder perforation, complicating between 2 and 10% of all operations, and on average 4.7%. It is usually corrected during surgery, with repositioning of the trocars. The purpose of this video is to demonstrate a method of replacing the trocars under direct vision. METHODS: This video exhibits a bladder perforation during insertion of a retropubic midurethral sling (Advantage Fit; Boston Scientific) and gives a step-by step guide to the removal and repositioning of the sling under direct visualisation. CONCLUSION: Repositioning of the trocars under direct vision in cases of bladder perforation may have numerous advantages. It may prevent damage to the urethra, possibly reduce the risk of postoperative infection and may be beneficial for trainees.

Impact of ethnicity on urodynamic outcomes.

The aim of this study was to assess the impact of ethnicity on urodynamic outcomes. The urodynamic studies (UDS) of 100 women were analysed; 41 were of white Caucasian origin, 35 of Asian origin and 24 of African origin. The presence of detrusor overactivity (DOA) in the three ethnic groups was compared and the nature of DOA in terms of cystometric capacity, volume of strong desire, maximum flow rate (Qmax), volume at which DOA occurred, mean amplitude of contraction and number of contractions, were compared. Asian (p < 0.003) and African (p < 0.008) women were more likely to have a diagnosis of DOA compared with white Caucasian women. There was no difference in UDS outcomes when comparing Asian and African Women. The ethnicity did not appear to impact significantly on the nature of the DOA. Women of Asian and African origin attending for UDS presented with DOA more commonly than those of white Caucasian origin.

Faecal incontinence persisting after childbirth: a 12 year longitudinal study.

OBJECTIVES: To investigate persistent faecal incontinence (FI) 12 years after birth and association with delivery mode history and quality of life. DESIGN: Twelve-year longitudinal study. SETTING: Maternity units in Aberdeen, Birmingham and Dunedin. POPULATION: Women who returned questionnaires 3 months and 12 years after index birth. METHODS: Data on all births over 12 months were obtained from units and women were contacted 3 months, 6 years and 12 years post birth. MAIN OUTCOME MEASURE: Persistent FI, defined as reported at 12 years and one or more previous contacts. SF12 assessed quality of life. RESULTS: Of 7879 women recruited at 3 months, 3763 responded at 12 years, 2944 of whom also responded at 6 years: nonresponders were similar in obstetric factors. Prevalence of persistent FI was 6.0% (227/3763); 43% of 12-year responders who reported FI at 3 months also reported it at 12 years. Women with persistent FI had significantly lower SF12 scores. Compared with only spontaneous vaginal deliveries, women who had one or more forceps delivery were more likely to have persistent FI (odds ratio [OR] 2.08, 95% confidence interval [95% CI] 1.53-2.85) but it was no less likely with exclusively caesarean births (OR 0.93, 95% CI 0.54-1.58). More obese women than normal weight women reported persistent FI (OR 1.52, 95% CI 1.06-2.17). CONCLUSIONS: This longitudinal study has demonstrated persistence of FI many years after birth and shown that one forceps birth increased the likelihood, whereas exclusive caesarean birth showed no association. Obesity, which increased symptom likelihood, is a modifiable risk factor.

Childbirth and prolapse: long-term associations with the symptoms and objective measurement of pelvic organ prolapse.

OBJECTIVES: To investigate prolapse symptoms and objectively measured pelvic organ prolapse, 12 years after childbirth, and association with delivery mode history. DESIGN: Twelve-year longitudinal study. SETTING: Maternity units in Aberdeen, Birmingham and Dunedin. POPULATION: Women dwelling in the community. METHODS: Data from women were collected 12 years after an index birth and women were invited for examination. Logistic regression investigated associations between risk factors and prolapse symptoms and signs. MAIN OUTCOME MEASURES: Prolapse symptom score (POP-SS); objectively measured prolapse (POP-Q). RESULTS: Of 7725 continuing women, 3763 (49%) returned questionnaires at 12 years. The median POP-SS score was 2 (IQR 0-4). One or more forceps deliveries (OR 1.20, 95% CI 1.04-1.38) and a body mass index (BMI) over 25 were associated with higher (worse) POP-SS scores, but age over 25 years at first delivery was associated with lower (better) scores. There was no protective effect if all deliveries were by caesarean section (OR 0.84, 95% CI 0.69-1.02). Objective prolapse was found in 182/762 (24%) women. Women aged over 30 years when having their first baby and parity were significantly associated with prolapse. Compared with women whose births were all spontaneous vaginal deliveries, women who had all births by caesarean section were the least likely to have prolapse (OR 0.11, 95% CI 0.03-0.38), and there was a reduced risk after forceps or a mixture of spontaneous vaginal delivery and caesarean section. CONCLUSIONS: These findings are at odds with each other, suggesting that prolapse symptoms and objective prolapse may not be in concordance, or are associated with different antecedent factors. Further follow-up is planned.

Age-related trends in urinary excretion of bisphenol A in Australian children and adults: evidence from a pooled sample study using samples of convenience.

Bisphenol A (BPA or 4,4'-(propane-2,2-diyl)diphenol) is a chemical intermediate in the production of polycarbonate and epoxy resins, and is used in a wide range of applications. BPA has attracted significant attention in the past decade due to its frequency of detection in human populations worldwide, and has demonstrated animal toxicity and potential impact on human health, particularly during critical periods of development. The aim of this study was to perform a preliminary assessment of age-related trends in urinary concentration and to estimate daily excretion of BPA in Australian children (aged >0 to <5 yr) and adults (≥15 to <75 yr). This was achieved using 79 samples pooled by age and gender, created from 868 individual samples of convenience collected as part of routine, community-based pathology testing. Total BPA was analyzed using online solid phase extraction (SPE)-liquid chromatography tandem mass spectrometry (LC-MS/MS) and detected in all samples with a range of 0.65-265 ng/ml. No significant differences were observed between males and females. A urine flow model was constructed from published values and was used to provide an estimate of daily excretion per unit body weight for each pooled sample. The daily excretion estimates ranged from 26.2 to 18,200 ng/kg-d for children, and from 20.1 to 165 ng/kg-d for adults. Urinary concentrations and estimated excretion rates were inversely associated with age, and estimated daily excretion in infants and young children was significantly higher than in adults (geometric mean: 107 and 47.0 ng/kg-d, respectively). Higher excretion of BPA in children may be explained by their higher food consumption relative to body weight compared to adults and adolescents, and may also reflect alternative exposure pathways and sources.

Bespoke magnetic field design for a magnetically shielded cold atom interferometer.

Quantum sensors based on cold atoms are being developed which produce measurements of unprecedented accuracy. Due to shifts in atomic energy levels, quantum sensors often have stringent requirements on their internal magnetic field environment. Typically, background magnetic fields are attenuated using high permeability magnetic shielding, with the cancelling of residual and introduction of quantisation fields implemented with coils inside the shield. The high permeability shield, however, distorts all magnetic fields, including those generated inside the sensor. Here, we demonstrate a solution by designing multiple coils overlaid on a 3D-printed former to generate three uniform and three constant linear gradient magnetic fields inside the capped cylindrical magnetic shield of a cold atom interferometer. The fields are characterised in-situ and match their desired forms to high accuracy. For example, the uniform transverse field, Bx, deviates by less than 0.2% over more than 40% of the length of the shield. We also map the field directly using the cold atoms and investigate the potential of the coil system to reduce bias from the quadratic Zeeman effect. This coil design technology enables targeted field compensation over large spatial volumes and has the potential to reduce systematic shifts and noise in numerous cold atom systems.

Proper understanding of recurrent stress urinary incontinence treatment in women (PURSUIT): a randomised controlled trial of endoscopic and surgical treatment.

BACKGROUND: Women with stress urinary incontinence (SUI) experience urine leakage with physical activity. Currently, the interventional treatments for SUI are surgical, or endoscopic bulking injection(s). However, these procedures are not always successful, and symptoms can persist or come back after treatment, categorised as recurrent SUI. There are longstanding symptoms and distress associated with a failed primary treatment, and currently, there is no consensus on how best to treat women with recurrent, or persistent, SUI. METHODS: A two-arm trial, set in at least 20 National Health Service (NHS) urology and urogynaecology referral units in the UK, randomising 250 adult women with recurrent or persistent SUI 1:1 to receive either an endoscopic intervention (endoscopic bulking injections) or a standard NHS surgical intervention, currently colposuspension, autologous fascial sling or artificial urinary sphincter. The aim of the trial is to determine whether surgical treatment is superior to endoscopic bulking injections in terms of symptom severity at 1 year after randomisation. This primary outcome will be measured using the patient-reported International Consultation on Incontinence Questionnaire - Urinary Incontinence - Short Form (ICIQ-UI-SF). Secondary outcomes include assessment of longer-term clinical impact, improvement of symptoms, safety, operative assessments, sexual function, cost-effectiveness and an evaluation of patients' and clinicians' views and experiences of the interventions. DISCUSSION: There is a lack of high-quality, randomised, scientific evidence for which treatment is best for women presenting with recurrent SUI. The PURSUIT study will benefit healthcare professionals and patients and provide robust evidence to guide further treatment and improve symptoms and quality of life for women with this condition. TRIAL REGISTRATION: International Standard Randomised Controlled Trials Number (ISRCTN) registry ISRCTN12201059. Registered on 09 January 2020.

Anaesthesia for incontinence surgery: spinal anaesthesia or sedation?

This was a patient and assessor blinded randomised controlled trial to compare the patient and surgeon's satisfaction for retropubic tapes inserted under sedation vs spinal anaesthesia and also looking at the bladder sensation following insertion of the tape. A total of 38 patients completed the study (19 in each group). The differences in mean visual analogue scores were in favour of spinal anaesthesia. The surgeon's assessment of patient cooperation was 24.2, 95% CI 9.6-38.8 p = 0.002, while for pain, the difference in the mean scores was -21.6, 95% CI -36.6 to -6.5, p = 0.006. The difference in the mean scores for the feeling of being in control was 21.4, 95% CI 0.85 to 41.63, p = 0.004. The only significant difference in bladder sensation postoperatively was the strong desire to void at 1 hour. This study demonstrates that spinal anaesthesia has better patient and surgeon satisfaction, with a difference in bladder sensation at 1 hour postoperatively.

Comparative analysis of three laboratory based serological assays for SARS-CoV-2 in an Australian cohort.

Many unanswered questions remain regarding the role of SARS-CoV-2 serological assays in this unfolding COVID-19 pandemic. These include their utility for the diagnosis of acute SARS-CoV-2 infection, past infection or exposure, correlation with immunity and the effective duration of immunity. This study examined the performance of three laboratory based serological assays, EUROIMMUN Anti-SARS-CoV-2 IgA/IgG, MAGLUMI 2000 Plus 2019-nCov IgM/IgG and EDI Novel Coronavirus (COVID-19) IgM/IgG immunoassays. We evaluated 138 samples from a reference non-infected population and 71 samples from a cohort of 37 patients with SARS-CoV-2 confirmed positive by RT-PCR. The samples were collected at various intervals of 0-45 days post symptoms onset (PSO). Specificity and sensitivity of these assays was 60.9%/71.4% (IgA) and 94.2%/63.3% (IgG) for EUROIMMUN; 98.5%/18.4% (IgM) and 97.8%/53.1% (IgG) for MAGLUMI; and 94.9%/22.5% (IgM) and 93.5%/57.1% (IgG) for EDI, respectively. When samples collected ≥14 days PSO were considered, the sensitivities were 100.0 and 100.0%; 31.0 and 82.8%; 34.5 and 57.1%, respectively. Using estimated population prevalence of 0.1, 1, and 10%, the positive predictive value of all assays remained low. The EUROIMMUN Anti-SARS-CoV-2 IgA lacked specificity for acute diagnosis and all IgM assays offered poor diagnostic utility. Seroconversion can be delayed although all patients had seroconverted at 28 days in our cohort with the EUROIMMUN Anti-SARS-CoV-2 IgG. Despite this, with specificity of only 94% this assay would not be satisfactory for seroprevalence studies in the general Australian population given this is likely to be currently <1%.

Colposuspension or TVT with anterior repair for urinary incontinence and prolapse: results of and lessons from a pilot randomised patient-preference study (CARPET 1).

In a multicentre randomised, unblinded patient preference pilot trial to assess the feasibility of a definitive randomised trial comparing colposuspension with tension-free vaginal tape (TVT) plus anterior repair in women with incontinence and prolapse, we found that 31 of 56 eligible women agreed to participate (55%). Recruitment was more successful face to face (87%) than by letter (16%). Only four of our women agreed to be randomised, 21 (68%) chose anterior repair+TVT and six (19%) chose colposuspension. This study demonstrates the importance of pilot work for complex trials to identify issues likely to adversely affect recruitment.

Per- and polyfluoroalkyl substances (PFAS) in Australia: Current levels and estimated population reference values for selected compounds.

BACKGROUND: Increased public awareness of PFAS contamination in Australia has resulted in serum biomonitoring efforts in individuals in potentially affected communities. However, population-based reference values for assessing whether individual results exceed the typical range in the Australian general population are not currently available. OBJECTIVE: Estimate population upper bound reference values based on updated serum PFAS concentrations in pooled samples from southeast Queensland, Australia and population variation observed in the US National Health and Nutrition Examination Survey (NHANES) datasets. METHODS: We calculated ratios of 95th percentile to arithmetic mean (P95:AM ratios) using data from the NHANES 2013-14 and 2015-16 cycle samples for frequently detected PFASs: PFOA, linear and branched PFOS, perfluorononanoate (PFNA), perfluorodecanoate (PFDA), and perfluorohexanesulfonate (PFHxS). We estimated Australian age-specific means for PFAS using pooled serum samples collected in 2014-15 and 2016-17. We used the P95:AM ratios to estimate 95th percentile concentrations in the Australian population based on the results of the 2016-17 pooled samples. RESULTS AND CONCLUSIONS: P95:AM ratios for each PFAS were similar across NHANES cycle and age group, so overall compound-specific ratios were estimated for PFOA (2.1), PFNA (2.4), PFDA (2.7), PFHxS (2.7), and linear (2.4) and summed PFOS (2.3). Australian mean PFAS concentrations continued previously reported declining trends. The estimated P95 values can be used as preliminary substitutes for more rigorous population reference values to identify samples with clearly elevated serum PFAS concentrations in Australian biomonitoring efforts. Given uncertainties and variability inherent in this evaluation, the estimated P95 values should be interpreted with caution. Mean and estimated P95 serum PFAS concentrations in Australia should continue to be monitored to document declining trends in population serum concentrations.

Does the mode of delivery predispose women to anal incontinence in the first year postpartum? A comparative systematic review.

OBJECTIVES: To assess if mode of delivery is associated with increased symptoms of anal incontinence following childbirth. DESIGN: Systematic review of all relevant studies in English. DATA SOURCES: Medline, Embase, Cochrane Library, bibliographies of retrieved primary articles and consultation with experts. STUDY SELECTION AND DATA EXTRACTION: Data were extracted on study characteristics, quality and results. Exposure to risk factors was compared between women with and without anal incontinence. Categorical data in 2 x 2 contingency tables were used to generate odds ratios. RESULTS: Eighteen studies met the inclusion criteria with 12,237 participants. Women having any type of vaginal delivery compared with a caesarean section have an increased risk of developing symptoms of solid, liquid or flatus anal incontinence. The risk varies with the mode of delivery ranging from a doubled risk with a forceps delivery (OR 2.01, 95% CI 1.47-2.74, P < 0.0001) to a third increased risk for a spontaneous vaginal delivery (OR 1.32, 95% CI 1.04-1.68, P = 0.02). Instrumental deliveries also resulted in more symptoms of anal incontinence when compared with spontaneous vaginal delivery (OR 1.47, 95% CI 1.22-1.78). This was statistically significant for forceps deliveries alone (OR 1.5, 95% CI 1.19-1.89, P = 0.0006) but not for ventouse deliveries (OR 1.31, 95% CI 0.97-1.77, P = 0.08). When symptoms of solid and liquid anal incontinence alone were assessed, these trends persisted but were no longer statistically significant. CONCLUSION: Symptoms of anal incontinence in the first year postpartum are associated with mode of delivery.

Magnetic resonance imaging in rectal cancer downstaged using neoadjuvant chemoradiation: accuracy of prediction of tumour stage and circumferential resection margin status.

OBJECTIVE: The aim was to examine the accuracy of magnetic resonance imaging (MRI) in predicting circumferential resection margin (CRM) involvement, T- and N-stage in patients with locally advanced carcinoma of the rectum, who had undergone long-course downstaging chemoradiation (CRT). METHOD: Patients with rectal cancer were selected for long-course downstaging CRT if their tumour was considered to threaten (< or = 1 mm) or involve the CRM on MRI. Eighty such patients had a repeat MRI at a median of 6 weeks post-CRT followed by surgical excision soon thereafter. The findings on the post-CRT MRI were compared with histological examination of the surgical specimen. RESULTS: For CRM involvement, post-CRT restaging MRI had an accuracy of 81% (65/80) a sensitivity of 54% (7/13), a specificity of 87% (58/67), a positive predictive value of 44% (7/16) and a negative predictive value of 91% (58/64). Accuracy for T- and N-staging was 43% (34/80) and 78% (62/80), respectively. 38% of T-stages were overstaged and 20% understaged. 4% of N-stages were overstaged and 19% understaged. The 13 patients with histological positive CRM had worse clinical outcomes than the 67 patients with negative CRM in terms of disease-free survival (relative risk of reduced DFS 4.6, P = 0.001) and overall survival (relative risk of death 3.6, P = 0.016). CONCLUSION: Magnetic resonance imaging has good specificity and negative predictive value for predicting an uninvolved CRM post downstaging CRT in locally advanced rectal cancer although sensitivity and positive predictive value for an involved CRM were unsatisfactory. The shortcomings of MRI stem from poor differentiation of viable tumour from posttreatment changes and inability to identify small nodal and tumour deposits. Clinical correlates in this group of patients have confirmed the importance of achieving a clear CRM at surgery.