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Endoscopic mucosal resection (EMR) is a cornerstone in the management of large (≥20 mm) non-pedunculated colorectal polyps. Clinically significant post-EMR bleeding occurs in 7% of cases and is most frequently encountered in the right colon. We aimed to assess the use of prophylactic clip closure in preventing clinically significant post-EMR bleeding within the right colon.We conducted a randomised controlled trial at a tertiary centre in Australia. Patients referred for the EMR of large non-pedunculated colorectal polyps in the right colon were eligible. Patients were randomly assigned (1:1) into the clip or control (no clip) group, using a computerised random-number generator. The primary endpoint was clinically significant post-EMR bleeding, defined as haematochezia necessitating emergency department presentation, hospitalisation, or re-intervention within 14 days post-EMR, which was analysed on the basis of intention-to-treat principles. The trial is registered with ClinicalTrials.gov, NCT02196649, and has been completed.Between Feb 4, 2016, and Dec 15, 2020, 231 patients were randomly assigned: 118 to the clip group and 113 to the control group. In the intention-to-treat analysis, clinically significant post-EMR bleeding was less frequent in the clip group than in the control group (four [3·4%] of 118 patients vs 12 [10·6%] of 113; p=0·031; absolute risk reduction 7·2% [95% CI 0·7-13·8]; number needed to treat 13·9). There were no differences between groups in adverse events, including delayed perforation (one [1%] in the clip group vs one [1%] in the control group) and post-EMR pain (four [3%] vs six [5%]). No deaths were reported.Prophylactic clip closure can be performed following the EMR of large non-pedunculated colorectal polyps of 20 mm or larger in the right colon to reduce the risk of clinically significant post-EMR bleeding.None.

BackgroundLocal anesthetic wound infusion catheters are increasingly used postmidline laparotomy to reduce pain and opioid use, however there is little evidence to support any particular infusion regime.MethodsA retrospective cohort study was undertaken of patients after midline laparotomy who had bilateral local anesthetic wound infusion catheters surgically placed. Patients were recruited into 3 cohorts: ropivacaine 0.2% 5–8 mL/hour continuous wound infusion, 10 mL programmed intermittent bolus 2 hourly, 20 mL programmed intermittent bolus 4 hourly. The primary outcome was the maximum daily Numerical Rating Pain Score with movement (dynamic pain score) recorded during first 96 hours postprocedure. Secondary outcomes included the maximum daily resting pain score and opioid utilization.ResultsIn three cohorts of 70 patients (n=210), the maximum daily dynamic pain score in the intermittent bolus 2-hourly and 4-hourly cohorts was lower when compared with the continuous infusion group over the first 4 postoperative days. The mean difference in maximum daily pain score with respect to the continuous infusion regime was 0.8 (95% CI 0.2 to 1.4) for the intermittent bolus 2-hourly group and 0.6 (95% CI 0.0 to 1.2) for the 4-hourly group. Generalized estimating equation modeling indicates the reduction in dynamic pain score is greatest with the intermittent bolus 2-hourly regime over the first 72 hours postprocedure. The 2-hourly intermittent bolus regime was also associated with lower opioid utilization and local anesthetic exposure.ConclusionsIntermittent wound infusion catheter infusion regimes were associated with lower maximum daily dynamic pain scores, although the magnitude of this change may be of limited clinical significance.

Background Cardiac rehabilitation (CR) programs reduce the risk of further cardiac events and improve the ability of people living with cardiovascular disease to manage their symptoms. However, many people who experience a cardiac event do not attend or fail to complete their CR program. Little is known about the characteristics of people who drop out compared to those who complete CR. Aims To identify subgroups of patients attending a cardiac rehabilitation program who are more likely to dropout prior to final assessment by (1) calculating the dropout rate from the program, (2) quantifying the association between dropout and socio-demographic, lifestyle, and cardiovascular risk factors, and (3) identifying independent predictors of dropout. Methods The study population is from a large metropolitan teaching hospital in Sydney, Australia, and consists of all participants consecutively enrolled in an outpatient CR program between 2006 and 2017. Items assessed included diagnoses and co-morbidities, quality of life (SF-36), psychological health (DASS-21), lifestyle factors and physical assessment. Dropout was defined as failure to complete the outpatient CR program and post CR assessment. Results Of the 3,350 patients enrolled in the CR program, 784 (23.4%; 95%CI: 22.0–24.9%) dropped out prior to completion. The independent predictors of dropout were smoking (OR 2.4; 95%CI: 1.9–3.0), being separated or divorced (OR 2.0; 95%CI: 1.5–2.6), younger age (

Objectives This study hypothesized that catheter ablation in healthy ovine ventricular myocardium using low ionic 0.45% saline (half-normal saline [HNS]) and nonionic 5% dextrose in water (D5W) would result in larger lesions compared with use of 0.9% saline (normal saline [NS]). Background Limited data exist regarding the safety and efficacy of catheter ablation using low and nonionic irrigants. Methods Open irrigated ablation was performed on 14 beating ovine hearts (NS, n = 5; HNS, n = 4; D5W, n = 5). Ablation was delivered by using identical parameters (ie, 30 W in power control mode, 60-second duration, contact force of 10-20 g in the endocardial ventricles and 5-10 g in the epicardium). Catheter orientation and tissue contact were optimized by using intracardiac echocardiography. Lesion width, depth, and volume and number of steam pops were compared. Results Overall, 196 lesions were analyzed (mean duration: 56.7 ± 8.3 seconds; mean contact force: 15.3 ± 6.1 g; and mean impedance drop: 31 ± 19.1 Ω). Compared with NS, HNS and D5W resulted in larger lesion volumes (NS 349.2 ± 245.1 mm3 vs HNS 645.7 ± 386.4 mm3 vs D5W 633.2 ± 387.1 mm3; HNS vs NS; P Conclusions Catheter ablation with HNS and D5W resulted in larger ablation lesions compared with NS but similar lesion dimensions between HNS and D5W. The increase in lesion size with HNS and D5W was associated with a higher incidence of steam pops, especially with D5W, compared with NS.

ObjectiveEndoscopic mucosal resection (EMR) in the colon has been widely adopted, but there is limited data on the histopathological effects of the differing electrosurgical currents (ESCs) used. We used an in vivo porcine model to compare the tissue effects of ESCs for snare resection and adjuvant margin ablation techniques.DesignStandardised EMR was performed by a single endoscopist in 12 pigs. Two intersecting 15 mm snare resections were performed. Resections were randomised 1:1 using either a microprocessor-controlled current (MCC) or low-power coagulating current (LPCC). The lateral margins of each defect were treated with either argon plasma coagulation (APC) or snare tip soft coagulation (STSC). Colons were surgically removed at 72 hours. Two specialist pathologists blinded to the intervention assessed the specimens.Results88 defects were analysed (median 7 per pig, median defect size 29×17 mm). For snare ESC effects, 156 tissue sections were assessed. LPCC was comparable to MCC for deep involvement of the colon wall. For margin ablation, 172 tissue sections were assessed. APC was comparable to STSC for deep involvement of the colon wall. Islands of preserved mucosa at the coagulated margin were more likely with APC compared with STSC (16% vs 5%, p=0.010).ConclusionFor snare resection, MCC and LPCC did not produce significantly different tissue effects. The submucosal injectate may protect the underlying tissue, and technique may more strongly dictate the depth and extent of final injury. For margin ablation, APC was less uniform and complete compared with STSC.

BackgroundABG samples are often obtained in trauma patients to assess shock severity. Venous blood gas (VBG) sampling, which is less invasive, has been widely used to assess other forms of shock. The study aim was to determine the agreement between VBG and ABG measurements in trauma.MethodsPatients were enrolled at an Australian trauma centre between October 2016 and October 2018. Bland-Altman limits of agreement (LOA) between paired blood gas samples taken ResultsDuring the study period 176 major trauma patients had valid paired blood gas samples available for analysis. The median time difference between paired measurements was 11 min (IQR 6–17). There was a predominance of men (81.8%) and blunt trauma (92.0%). Median Injury Severity Score was 13 (range 1–75) and inpatient mortality was 6.3%. Mean difference (ABG−VBG) and LOA between paired arterial and venous measurements were 0.036 (LOA −0.048 to 0.120) for pH, −1.27 mmol/L (LOA −4.35 to 1.81) for BD, −0.64 mmol/L (LOA −1.86 to 0.57) for lactate and −1.97 mmol/L (LOA −5.49 to 1.55) for bicarbonate. Independent assessment of the VBG ‘false negative’ cases (n=20) suggested an ABG would change circulatory management in two cases.ConclusionsIn trauma patients VBG and ABG parameters displayed suboptimal agreement. However, in cases flagged as VBG ‘false negative’ independent review indicated that the availability of an ABG was unlikely to change management.

Patients with chronic kidney disease (CKD) are at increased risk of adverse cardiovascular events, which is underestimated by traditional risk stratification algorithms. We sought to determine clinical and echocardiographic predictors of adverse outcomes in CKD patients.Two hundred forty-three prospectively recruited stage 3/4 CKD patients (male, 63%; mean age, 59.2 ± 14.4 years) without previous cardiac disease made up the study cohort. All participants underwent a transthoracic echocardiogram, with left ventricular (LV) and left atrial (LA) strain analysis. Participants were followed for 3.9 ± 2.7 years for the primary end point of cardiovascular death and major adverse cardiovascular event (MACE). The secondary end point was the composite of all-cause death and MACE.Fifty-four patients met the primary end point, and 65 the secondary end point. On log-rank tests, older age, diabetes mellitus, anemia, greater LV mass, reduced LV global longitudinal strain, larger indexed LA volume, higher E/e' ratio, and reduced LA reservoir strain (LASr; P .01 for all) were independent predictors of cardiovascular death and MACE. On multivariable regression analysis of univariate predictors, LASr (P .01) was the only independent predictor for the primary end point as well as for the secondary end point. Receiver operating characteristic curve analysis showed LASr was a stronger predictor of adverse events (area under the curve [AUC] = 0.84) compared to the Framingham (AUC = 0.58) and Atherosclerotic Cardiovascular Disease (AUC = 0.59) risk scores.LASr is an independent predictor of cardiovascular death and MACE in CKD patients, superior to clinical risk scores, LV parameters, and LA volume.

BACKGROUND Left atrial (LA) deformation during the reservoir phase (LASr) has demonstrated strong prognostic value in different clinical settings. Although determinants of left atrial reservoir strain including left atrial relaxation, left atrial compliance, and left ventricular longitudinal systolic function are fairly well defined, there is incomplete information regarding the effect of left atrial volume on this relationship which is the focus of our study. METHOD Consecutive patients without prior cardiac disease referred for transthoracic echocardiography were prospectively recruited. All participants underwent clinical assessment, transthoracic echocardiography (TTE), and screening exercise stress test. Only patients with normal left ventricular ejection fraction (LVEF) without left ventricular hypertrophy (LVH) or myocardial ischemia on stress testing were included. RESULTS A total of 260 patients (57% male, mean age 59 ± 14 years) were included. 70% had hypertension, 33% had diabetes mellitus, and 31% had both HTN and DM. On multivariate analysis, age, e', LAVI, and LV GLS (P

Grindr is a geolocation smartphone application popular among men who have sex with men (MSM) to find sexual partners. We conducted a study to assess if attendance and HIV testing amongst MSM increased due to advertisements on Grindr that promoted our service. We measured clinic website hits by users clicking through from Grindr; we counted self-reported registrations that nominated referral from Grindr; and we compared new patient attendances and HIV tests in MSM with heterosexual men, for the 18 months preceding the intervention and the 18 months of the intervention. During the intervention the clinic’s website received 11,799 unique hits from Grindr users. The average monthly rate of attendances by new MSM increased 70.3% from 19.0 to 32.3, compared with a 5.5% increase among new heterosexual men from 45.6 to 48.1. The average monthly rate of HIV tests among MSM increased 43.6% from 47.0 to 67.6, compared with a 3.9% increase amongst heterosexual men from 40.0 to 41.6. The MSM:heterosexual men rate ratio for new patient attendances changed from 0.42 to 0.67 ( p

To determine the prevalence of metabolic dysfunction-associated fatty liver disease (MAFLD) and its association on adverse pregnancy outcomes in women with gestational diabetes mellitus (GDM).380 women with GDM had a FibroScan® performed between 24 and 32 weeks. A Controlled Attenuation Parameter (CAP) ≥ 233.5 dB/m signified MAFLD. Gestational hypertension, pre-eclampsia and eclampsia contributed to a composite of adverse maternal outcomes. A composite of adverse neonatal outcomes included pre-term birth, hypoglycaemia, small/large-for-gestational age and admission to neonatal high dependency. Multiple logistic regression was used to determine independent associations with MAFLD.147 (38.7 %) women had MAFLD. Higher pre-pregnancy BMI (median 28.4, IQR 24.7-33.0 kg/mWithin this GDM cohort, almost 40% had FibroScan®-detected MAFLD in mid-to-late gestation. MAFLD was not associated with worse pregnancy outcomes.

Metabolic dysfunction-associated fatty liver disease (MAFLD) can develop in any patient, including those with chronic hepatitis C (CHC). The recently proposed diagnostic criteria for MAFLD provide a unique opportunity to investigate the impact of concomitant fatty liver in patients with another established cause for their liver disease. The objective of our study was to assess the characteristics and outcomes of patients with a dual etiology liver disease.We evaluated 1181 patients including 744 with CHC and 437 with MAFLD. All patients in both cohorts underwent liver biopsy indicating disease activity and fibrosis stage.Nearly half (43.1%) the patients with CHC had concomitant MAFLD. Comparing patients with CHC alone with those with a dual etiology disease, we found that the latter had more severe liver injury, hepatic inflammation and fibrosis (all P 0.001). Interestingly, lean or normal-weight patients with CHC and MAFLD had a similar fibrosis stage compared to the two other subgroups of MAFLD (obesity and/or diabetes mellitus). There was no statistical significance in hepatic steatosis and fibrosis between genotype 3 CHC and MAFLD group compared to other genotypes.Patients with CHC and concomitant MAFLD had more severe liver disease than those with viral hepatitis alone. Recognizing coexisting MAFLD in patients with CHC is important for the delivery of holistic care.

The risk of cancer in large nonpedunculated colorectal polyps ≥20 mm (LNPCPs) in the rectum relative to the remainder of the colon is unknown. We aimed to describe differences between rectal and colonic LNPCPs to better inform treatment decisions.Patients with LNPCPs referred to tertiary centers for endoscopic resection within a prospective, multicenter, observational cohort were evaluated. Data recorded were participant demographics, LNPCP location, morphology, resection modality, and histopathologic data. Multiple logistic regression analysis was used to identify those variables independently associated with rectal versus nonrectal location in the colon.Patients with LNPCPs referred for endoscopic resection between July 2008 and July 2021 were included. Rectal LNPCPs (n = 618) were larger (median size, 40 mm vs 30 mm; P .001) and more likely to be granular (79% vs 50%, P .001) with a nodular component (53% vs 17%, P .001) compared with nonrectal LNPCPs (n = 2787). Rectal LNPCPs were more likely to have tubulovillous histopathology (72% vs 47%, P .001) and contain cancer (15% vs 6%, P .001). After adjusting for the other features independently associated with location, cancer was more common in the rectum compared with the colon (odds ratio, 1.77; 95% confidence interval, 1.25-2.53).This study suggests that compared with LNPCPs in the rest of the colon, rectal LNPCPs are more likely to be larger and contain more advanced pathology. These findings have implications for curative endoscopic resection techniques particularly where early cancer is present. (Clinical trial registration numbers: NCT01368289 and NCT02000141.).

BACKGROUND As the availability of Mohs micrographic surgery (MMS) continues to expand in Australia and incidence of keratinocyte cancer increases in adolescents and young adults, there has been rising interest in the use of MMS in this population. OBJECTIVE This study aimed to evaluate the characteristics of MMS cases in patients younger than 40 years. METHODS A review was performed of all MMS cases in patients younger than 40 years at the time of their surgery from 2012 to 2017 at the Skin and Cancer Foundation Australia, with comparison to a control group, aged older than 40 years. Patient, tumor and management characteristics were analyzed. RESULTS Four hundred ninety-three cases were eligible. Study and control groups differed significantly regarding gender (p < .001), tumor pathology (p < .001), anatomic site of tumor (p < .001), Mohs surgery stages (p = .039), defect size (p < .001), and repair method (p < .001). LIMITATIONS Retrospective study at a single institution. CONCLUSION Mohs micrographic surgery cases in patients younger than 40 years exhibit unique patient and tumor characteristics influencing choice of repair method.

IntroductionMechanical cardiopulmonary resuscitation (M-CPR) is increasingly used in the management of cardiac arrest. There are no previously reported randomised studies investigating M-CPR training. This study of newly trained M-CPR providers hypothesised that a brief simulation-based intervention after 4 months would improve M-CPR performance at 6 months.MethodsThis study used a simulated ‘in situ’ cardiac arrest model. The M-CPR device used was a proprietary Lund University Cardiac Assist System 3 machine (Physio Control, Redmond, Washington, USA). Standardised baseline training was provided to all participants. Following training, baseline performance was assessed. The primary outcome measure was the time taken to initiate M-CPR and the secondary outcome was performance against a checklist of errors. Participants were then randomised to intervention group (simulation training) or control group (routine clinical use of M-CPR). After 6 months the outcome measures were reassessed. Comparative statistical tests used an intention-to-treat analysis.Results112 participants were enrolled. The intervention group (n=60) and control group (n=52) had similar demographic characteristics. At the 6-month assessment, median time to M-CPR initiation was 27.0 s (IQR 22.0–31.0) in the intervention group and 31.0 s (IQR 25.6–46.0) in the control group (p=0.003). The intervention group demonstrated fewer errors compared with controls at 6 months (pConclusionIn this randomised study of approaches to M-CPR training, providers receiving additional simulation-based training had higher retention levels of M-CPR skills. Therefore, when resuscitation skills are newly learnt, provision follow-up training should be an important consideration.

Iodine supplements are recommended for women planning pregnancy, but their impact on thyroid function during controlled ovarian hyperstimulation (COH) and into pregnancy is unknown. The aim of this study was to assess the impact of iodine supplementation on thyroid function during COH.One-hundred and six euthyroid women (thyroid stimulating hormone (TSH) 0.4-2.5 mIU/L) planning their first COH cycle were subdivided according to iodine supplementation (nil,6 months, ≥6 months) and compared to levothyroxine (LT4)-treated controls. Serial TSH, free thyroxine, free triiodothyronine and thyroglobulin (Tg) levels were recorded at four time points: (i) baseline, (ii) day 7 ovarian stimulation, (iii) ovulation trigger and (iv) two weeks post oocyte retrieval. Oocyte numbers, fertilisation rates and pregnancy outcome were recorded.TSH increased during COH for those women taking iodine supplements for ≥6 months (P = 0.025). One quarter recorded a TSH level2.5 mIU/L before embryo transfer. A similar increase in TSH was demonstrated by LT4-dependent controls (P = 0.024) but not the remaining subgroups. Tg levels did not change during COH in any group but decreased significantly post oocyte retrieval if nil iodine (P 0.0001) or supplemented for ≥6 months (P 0.005). Iodine supplementation did not influence oocyte count, fertilisation or implantation rates. Women taking iodine for6 months were four times more likely to achieve a live birth than women taking iodine for longer.Women taking iodine supplements for ≥6 months are less able to adapt to the thyroidal demands of COH, with responses comparable to LT4-dependent patients.

Background Subclinical left ventricular dysfunction detected by 2‐dimensional global longitudinal strain post breast radiotherapy has been described in patients with breast cancer. We hypothesized that left ventricular dysfunction postradiotherapy may be site specific, based on differential segmental radiotherapy dose received. Methods and Results Transthoracic echocardiograms were performed at baseline, 6 weeks, and 12 months postradiotherapy on 61 chemotherapy‐naïve women with left‐sided breast cancer undergoing tangential breast radiotherapy. Radiation received within basal, mid, and apical regions for the 6 left ventricular walls was quantified from the radiotherapy treatment planning system. Anterior, anteroseptal, and anterolateral walls received the highest radiation doses, while inferolateral and inferior walls received the lowest. There was a progressive increase in the radiation dose received from basal to apical regions. At 6 weeks, the most significant percentage deterioration in strain was seen in the apical region, with greatest reductions in the anterior wall followed by the anteroseptal and anterolateral walls, with a similar pattern persisting at 12 months. There was a within‐patient dose–response association between the segment‐specific percentage deterioration in strain at 6 weeks and 12 months and the radiation dose received. Conclusions Radiotherapy for left‐sided breast cancer causes differential segmental dysfunction, with myocardial segments that receive the highest radiation dose demonstrating greatest strain impairment. Percentage deterioration in strain observed 6 weeks postradiotherapy persisted at 12 months and demonstrated a dose–response relationship with radiotherapy dose received. Radiotherapy‐induced subclinical cardiac dysfunction is of importance because it could be additive to chemotherapy‐related cardiotoxicity in patients with breast cancer. Long‐term outcomes in patients with asymptomatic strain reduction require further investigation.

Objective To investigate the pattern of change in muscle overactivity during repetitive grasp/release using dynamic computerized dynamometry (DCD; objective 1) and the effect of botulinum toxin A (BTX-A; objective 2). Design Secondary analysis of an observational cohort study. Setting Hospital outpatient spasticity management service. Participants A convenience sample (N=65), comprising adults with upper motor neuron syndrome affecting the arm after acquired brain injury (ABI; n=38) and participants without ABI (n=27). Interventions After clinical assessment, a subgroup of participants with ABI (n=28) underwent BTX-A injections as part of their spasticity management. Main Outcome Measures Post hoc DCD data processing extracted the values of minimum force generation between 10 sequential contractions. The pattern of change was analyzed. Results The ABI injected group exerted greater force at baseline than both other groups (ABI injected=1.04 kg, ABI noninjected=0.74 kg, participants without ABI=0.53 kg; P=.011). After the first contraction, minimum force values increased for all groups and were greatest in the ABI injected group. With subsequent cycles, the group without ABI showed a linear pattern of decreasing force generation, whereas both ABI groups showed a quadratic increasing pattern, which was of greater magnitude in the ABI injected group. After injection, values for the ABI injected group showed a 51% reduction in inducible muscle overactivity (P=.003) to magnitudes similar to those of the ABI noninjected group. Conclusions This study showed that hand relaxation deteriorated during repetitive movements in people with spasticity, a feature hypothesized to adversely influence everyday hand function. After BTX-A injection, the magnitude but not the pattern of this inducible muscle overactivity improved.

Background While multidisciplinary teams (MDTs) are now considered an essential part of cancer care decision-making, how they perform varies widely. The authors hypothesised that a comprehensive, multipronged improvement program, and associated annual member survey, could strengthen MDT performance across a whole cancer service. Methods The study comprised the introduction of a structured program, the Tumour Program Strengthening Initiative (TPSI) linked with an annual survey of member’s perceptions of their performance. Three iterations of the survey have been completed (2017, 2018 and 2019). Generalised estimating equations (GEEs) were used to test for a difference in the proportion of positive survey responses between 2017 and 2019 adjusted for team clustering. Results Twelve teams participated in TPSI. One hundred twenty-nine, 118 and 146 members completed the survey in 2017, 2018 and 2019, respectively. Of the 17 questions that were asked in all three years, nine showed significant improvement and, of these, five were highly significant. Documenting consensus, developing Terms of Reference (TORs), establishing referral criteria and referring to clinical practice guidelines showed most improvement. Questions related to patient considerations, professional development and quality improvement (QI) activities showed no significant change. Conclusions TPSI resulted in sustained and significant improvement. The MDT survey not only allowed MDT members to identify their strengths and weaknesses but also provided insights for management to flag priority areas for further support. Overall program improvement reflected the strengthening of the weakest teams as well as further improvement in highly performing MDTs. Importantly, the initiative has the potential to achieve behaviour change amongst clinicians.

Most clinical studies, which investigate the impact of therapy simultaneously, record the frequency of adverse events in order to monitor safety of the intervention. Study reports typically summarise adverse event data by tabulating the frequencies of the worst grade experienced but provide no details of the temporal profiles of specific types of adverse events. Such 'toxicity profiles' are potentially important tools in disease management and in the assessment of newer therapies including targeted treatments and immunotherapy where different types of toxicity may be more common at various times during long-term drug exposure. Toxicity profiles of commonly experienced adverse events occurring due to exposure to long-term treatment could assist in evaluating the costs of the health care benefits of therapy. We show how to generate toxicity profiles using an adaptation of the ordinal time-to-event model comprising of a two-step process, involving estimation of the multinomial response probabilities using multinomial logistic regression and combining these with recurrent time to event hazard estimates to produce cumulative event probabilities for each of the multinomial adverse event response categories. Such a model permits the simultaneous assessment of the risk of events over time and provides cumulative risk probabilities for each type of adverse event response. The method can be applied more generally by using different models to estimate outcome/response probabilities. The method is illustrated by developing toxicity profiles for three distinct types of adverse events associated with two treatment regimens for patients with advanced breast cancer.

Background Left atrial (LA) function plays a pivotal role in modulating left ventricular performance. The aim of our study was to evaluate the relationship between resting LA function by strain analysis and exercise capacity in patients with chronic kidney disease (CKD) and evaluate its utility compared with exercise E/e'. Methods and Results Consecutive patients with stage 3 and 4 CKD without prior cardiac history were prospectively recruited from outpatient nephrology clinics and underwent clinical evaluation and resting and exercise stress echocardiography. Resting echocardiographic parameters including E/e' and phasic LA strain (LA reservoir [LASr], conduit, and contractile strain) were measured and compared with exercise E/e'. A total of 218 (63.9±11.7 years, 64% men) patients with CKD were recruited. Independent clinical parameters associated with exercise capacity were age, estimated glomerular filtration rate, body mass index, and sex ( P P P P =0.20 on DeLong test). A model combining LASr and clinical metrics showed robust association with metabolic equivalents achieved in patients with CKD. Conclusions LASr, a marker of decreased LA compliance is an independent correlate of exercise capacity in patients with stage 3 and 4 CKD, with similar diagnostic value to exercise E/e'. Thus, LASr may serve as a resting biomarker of functional capacity in this population.

Atypical femur fractures (AFF) are a rare but serious complication of long-term bisphosphonate use. Although clearly defined by ASBMR criteria, a proportion of patients with AFFs may go unrecognized and the use of qualitative fracture criteria may lead to uncertainty in AFF diagnosis, with significant therapeutic implications. A score that rapidly and accurately identifies AFFs among subtrochanteric femur fractures using quantitative, measurable parameters is needed. In a retrospective cohort of 110 female patients presenting with AFFs or typical femur fractures (TFFs), multiple logistic regression and decision tree analysis were used to develop the Sydney AFF score. This score, based on demographic and femoral geometry variables, uses three dichotomized independent predictors and adds one point for each: (age ≤80 years) + (femoral neck width

Background & Aims Although perforation is the most feared adverse event associated with endoscopic mucosal resection (EMR), limited data exists concerning its management. Therefore, we sought to evaluate the short- and long-term outcomes of intra-procedural deep mural injury (DMI) in an international multi-center observational cohort of large (≥20 mm) non-pedunculated colorectal polyps (LNPCPs). Methods Consecutive patients who underwent EMR for a LNPCP ≥20 mm were evaluated. Significant DMI (S-DMI) was defined as Sydney DMI Classification type III (muscularis propria injury, target sign) or type IV/V (perforation without or with contamination, respectively). The primary outcome was successful S-DMI defect closure. Secondary outcomes included technical success (removal of all visible polypoid tissue during index EMR), surgical referral and recurrence at first surveillance colonscopy (SC1). Results Between July 2008 to May 2020, 3717 LNPCPs underwent EMR. Median lesion size was 35mm (interquartile range (IQR) 25 to 45mm). Significant DMI was identified in 101 cases (2.7%), with successful defect closure in 98 (97.0%) using a median of 4 through-the-scope clips (TTSCs; IQR 3 to 6 TTSCs). Three (3.0%) patients underwent S-DMI-related urgent surgery. Technical success was achieved in 94 (93.1%) patients, with 46 (45.5%) admitted to hospital (median duration 1 day; IQR 1 to 2 days). Comparing LNPCPs with and without S-DMI, no differences in technical success (94 (93.1%) vs 3316 (91.7%); P = .62) or SC1 recurrence (12 (20.0%) vs 363 (13.6%); P = .15) were identified. Conclusions Significant DMI is readily managed endoscopically and does not appear to affect technical success or recurrence.

Left atrial strain (LAS) on transthoracic echocardiogram (TTE) is increasingly recognised to have clinical utility in cardiovascular disease. Differences in LAS measurements between vendors remains a barrier for clinical use. We sought to compare LAS between two commonly used software platforms; the layer-specific endocardial and mid-myocardial measurements of LAS on General Electric (GE) Echopac were compared to TomTec strain. LAS was measured in 88 individuals with no previous cardiac history and 40 paroxysmal AF (PAF) patients, in sinus rhythm at TTE. Conventionally, LAS measured using GE Echopac is mid-myocardial strain (GE-mid); additionally, endocardial (GE-endo) LAS was evaluated. Both LAS measurements by GE were compared to TomTec-Arena (v2.30.02) measurements. Reservoir (ƐR), contractile (ƐCT) and conduit (ƐCD) phasic strain were evaluated. Both GE-mid and GE-endo LAS correlated well with TomTec LAS. On Bland-Altman analysis, GE-mid LAS measurements were systematically lower than TomTec LAS (ƐR: mean difference (MD) - 6.08%, limits of agreement (LOA) - 12%, 0%, ƐCT: MD - 0.8%, LOA - 7%, 5%, ƐCD: MD - 5.2% LOA - 12%, 1%). GE-endo LAS demonstrated no systematic difference from TomTec LAS, but had wider limits of agreement (ƐR: MD 0.41%, LOA - 7%, 8%, ƐCT: MD 0.50%, LOA - 6%, 7%, ƐCD: MD - 0.08%, LOA - 7%, 7%). ƐR had the best reproducibility. Mid-myocardial LAS, routinely evaluated by GE Echopac software, systematically underestimates LAS compared to TomTec. Using GE endocardial LAS eliminated this bias, but introduced greater variation between measurements. Serial measurements of LAS should therefore be performed on the same vendor system.

The purpose of this study was to evaluate whether dose to the skin surface underneath bolus, was accurately predicted by a 3D treatment planning system (TPS) in patients receiving 50 Gy/25# postmastectomy radiotherapy (PMRT) using optically stimulated luminescent dosimetry (OSLD) for verification. In vivo dosimetry using OSLDs was performed in 20 consecutive patients receiving PMRT. An array of 9 OSLDs were applied to the chest wall or neobreast in a grid arrangement. Dosimetry data were recorded on 3 separate treatment fractions, averaged, and extrapolated to 25 fractions. On the 3D TPS, the predicted dose was calculated using the departmental planning algorithm at points corresponding to the OSLDs. The mean within patient difference between the planned and measured dose at each of the 9 points was calculated and Bland-Altman limits of agreement used to quantify the extent of agreement. Paired t-tests were used to test for evidence of systematic bias at each point. The coefficient of variation of the 3 OSLD readings per patient at each of the 9 points was low for 8 points (≤4.4%) demonstrating comparable dose received per fraction at these points. The mean ratio between the in vivo measured extrapolated OSLD (IVME OSLD) dose and the planned TPS dose ranged between 0.97 and 0.99 across all points (standard deviation range 0.05 to 0.08). The mean within patient difference between the IVME OSLD and planned TPS was1 Gy at 7 of the 9 points and the t-test for evidence of systematic bias was significant (p = 0.03) at only 1 of the 9 points. Our commercially available 3D TPS closely predicted PMRT skin surface dose underneath bolus as verified by OSLDs. At all sites, the average ratio of delivered to predicted dose was0.97 but1. This practical and feasible OSLD assessment of only 3 of 25 fractions facilitates quality assurance of a TPS in predicting skin surface dose under bolus.

Background and Aims Clinically significant post-EMR bleeding (CSPEB) is the most-frequent serious adverse event after EMR of large laterally spreading colonic lesions (LSLs). There is no proven prophylactic therapy, and it remains a significant drawback of EMR. We aimed to systematically describe and evaluate the features of the post-EMR mucosal defect (PED) and their relationship to CSPEB. Methods A prospective study of LSLs referred for EMR at a tertiary center was performed. PEDs without visible features were recorded as bland blue. Nonbland blue (NBB) PED features included size, number, and herniation of submucosal vessels and presence of submucosal hemorrhage, fibrosis, fat, and exposed muscle. NBB PEDs were analyzed for association with CSPEB, defined as bleeding occurring after completion of the procedure necessitating readmission or reintervention. Results From April 2012 to May 2017, 501 lesions in 501 patients were eligible for analysis. The frequency of CSPEB was 30 of 501 (6.0%). More than or equal to 3 visible vessels was a significant predictor of CSPEB (P = .016). None of the following showed a significant correlation with CSPEB: presence of visible vessels, their diameter, herniation, or other nonvascular PED features. Submucosal vessels were more common in the left-sided colon segment (88.6% vs 78.3%, P = .004) and were significantly larger (20.8% vs 12.1% ≥1 mm, P = .037), more numerous (median 4 vessels [interquartile range, 2-7] vs 2 vessels [interquartile range, 1-4], P Conclusions More than or equal to 3 visible vessels within the PED may be predictive for CSPEB and may define a target group for real-time prophylactic intervention. No other endoscopically visible features of the PEDs were predictive of CSPEB. (Clinical trial registration number: NCT03117400 .)

Introduction The impact of sleep disordered breathing (SDB) on arterial intima-media thickness (IMT), a surrogate measure for cardiovascular disease, remains uncertain, in part because of the potential for non-SDB vascular risk factor interactions. In the present study, we determined predictors for common carotid (CCA) and femoral (CFA) artery IMT in an adult, sleep clinic cohort where non-SDB vascular risk factors (particularly diabetes) were eliminated or controlled. Methods We recruited 296 participants for polysomnography (standard SDB severity metrics) and CCA/CFA ultrasound examinations, followed by a 12 month vascular risk factor minimisation (RFM) and continuous positive pressure (CPAP) intervention for participants with a range of SDB severity (RFM Sub-Group, n = 157; apnea hyponea index [AHI]: 14.7 (7.2–33.2), median [IQR]). Univariable and multivariable linear regression models determined independent predictors for IMT. Linear mixed effects modelling determined independent predictors for IMT change across the intervention study. P Results Age, systolic blood pressure and waist:hip ratio were identified as non-SDB predictive factors for CCA IMT and age, weight and total cholesterol:HDL ratio for CFA IMT. No SDB severity metric emerged as an independent predictor for either CCA or CFA IMT, except in the RFM Sub-Group, where a 2-fold increase in AHI predicted a 2.4% increase in CFA IMT. Across the intervention study, CCA IMT decreased in those who lost weight, but there was no CPAP use interaction. CFA IMT, however, decreased by 12.9% (95%CI 6.8, 18.7%, p = 0.001) in those participants who both lost weight and used CPAP > = 4hours/night. Conclusion We conclude that SDB severity has little impact on CCA IMT values when non-SDB vascular risk factors are minimised or not present. This is the first study, however, to suggest a potential linkage between SDB severity and CFA IMT values. Trial registration Australian New Zealand Clinical Trials Registry, ACTRN12611000250932 and ACTRN12620000694910.

ObjectiveThe aim of the study was to assess the utility of a novel amyotrophic lateral sclerosis (ALS) diagnostic index (ALSDI).MethodsA prospective multicenter study was undertaken on patients presenting with suspected ALS. The reference standard (Awaji criteria) was applied to all patients at recruitment. Patients were randomly assigned to a training (75%) and a test (25%) cohort. The ALSDI was developed in the training cohort and its diagnostic utility was subsequently assessed in the test cohort.ResultsA total of 407 patients were recruited, with 305 patients subsequently diagnosed with ALS and 102 with a non-ALS mimicking disorder. The ALSDI reliably differentiated ALS from neuromuscular disorders in the training cohort (area under the curve 0.92, 95% confidence interval 0.89–0.95), with ALSDI ≥4 exhibiting 81.6% sensitivity, 89.6% specificity, and 83.5% diagnostic accuracy. The ALSDI diagnostic utility was confirmed in the test cohort (area under the curve 0.90, 95% confidence interval 0.84–0.97), with ALSDI ≥4 exhibiting 83.3% sensitivity, 84% specificity, and 83.5% diagnostic accuracy. In addition, the diagnostic utility of the ALSDI was confirmed in patients who were Awaji negative at recruitment and in those exhibiting a predominantly lower motor neuron phenotype.ConclusionThe ALSDI reliably differentiates ALS from mimicking disorders at an early stage in the disease process.Classification of evidenceThis study provides Class I evidence that for patients with suspected ALS, the ALSDI distinguished ALS from neuromuscular mimicking disorders.

Objective The feasibility and effectiveness of concomitant use of transcranial direct current stimulation (tDCS) with electroconvulsive therapy (ECT) has not been investigated. The study principally aimed at determining whether tDCS when combined with ECT improved the speed of antidepressant response. Secondarily, the ease of generation of seizures during electroconvulsive therapy and cognitive outcomes were investigated. Methods Consecutive patients referred for ECT to treat major depression were randomized to tDCS with dorsolateral prefrontal electrode placements (n = 8) or sham (n = 8) used daily and just before thrice weekly, 6 times threshold, right unilateral ultrabrief (0.3 ms) pulse width ECT. Change of depression severity was determined using the Montgomery Asberg Depression Rating Scale along with cognitive assessments using Montreal Cognitive Assessment and visual memory testing at weeks 1 and 2, which were compared with baseline. Results Change of depression severity from baseline was similar in tDCS and ECT compared with sham tDCS and ECT at week1 (mean [standard deviation {SD}] = 16.00 [6.78]; 13.75 [7.83]; P = 0.89) and at week 2 (mean [SD] = 23.00 [4.96]; 19.75 [9.85], P = 0.08). No between-group differences were obtained in the cognitive tests at weeks 1 and 2. Combining tDCS with ECT resulted in higher restimulation: 62.5% requiring 3 stimulations to achieve threshold in contrast to 12.5% with sham tDCS and ECT (P = 0.04). The mean suprathreshold dose was higher in the tDCS and ECT group compared with sham tDCS and ECT: mean [SD] = 144.0 [43.54] and mean [SD] = 122.4 [20.36], P = 0.04, respectively. Conclusions Concomitant use of tDCS with ultrabrief right unilateral ECT is feasible and safe albeit with higher rates of restimulation when tDCS was combined with ECT. However, there were no statistically significant differences in the speed of antidepressant response or cognitive outcomes at weeks 1 and 2 after the commencement of treatments.

Excessive gestational weight gain is associated with detrimental outcomes to both the mother and baby. Currently, the best approach to prevent excessive gestational weight gain in overweight and obese women is undetermined. The present study aimed to evaluate the effectiveness of a group-based outpatient dietary intervention in pregnancy to reduce excessive gestational weight gain. In this retrospective study, overweight and obese pregnant women who attended a single 90-min group education session were compared to women who received standard care alone. Total gestational weight gain, maternal and neonatal outcomes were compared between the intervention and control groups. Data were analysed using Student t, Mann–Whitney and Chi-squared tests as appropriate. A 24-h dietary recall was analysed and compared to the Australian National Nutrition Survey. A significant reduction in gestational weight gain was observed with this intervention (P = 0.010), as well as in the rate of small for gestational age births (P = 0.043). Those who attended the intervention had saturated fat and sodium intake levels that exceeded recommendations. Intake of pregnancy-specific micronutrients including folate, calcium and iron were poor from diet alone. A low-intensity antenatal dietary intervention may be effective in reducing excessive gestational weight gain, although multi-disciplinary interventions yield the best success. Further research is required to identify the optimal modality and frequency to limit excessive gestational weight gain. Dietary interventions tailored to ethnicity should also be explored. Level II, controlled trial without randomization.

Background Multidisciplinary teams (MDTs) are considered the “gold standard” of care for patients with cancer but how well they function and the role they play in decision making varies widely. Although several observational tools have been developed to evaluate MDT performance, they are resource intensive and only assess MDT performance at a static point in time. The aim of this study was to develop a validated maturity model as a self-assessment instrument for MDTs to evaluate their performance and monitor improvement over time. Methods The authors used a three-phase methodology to develop a maturity model. In the first phase, using a modified Delphi technique, we identified 20 indicators (within five components), each having five levels of maturity [1] . In the second phase, further Delphi iterations were undertaken to refine the content and structure of the model. By the end of the second phase six components and 17 indicators had been established. In the third phase, the refined model was distributed to members from 11 MDTs to test for validity and reliability. 101 valid responses were received. Principal Component Analysis was used to determine the optimal number of components that fit the indicators. Factors with eigenvalue greater than one were extracted. Cronbach’s alpha (α) was used to measure the internal consistency of components. Bivariate correlation analysis, measuring pair-wise relationships between indicators (r), was undertaken to assess convergent and discriminant validity. Results Five factors were extracted from Principal Component Analysis. For the factors extracted, 16 out of 17 indicators showed loadings greater than the 0.4 threshold. All components demonstrated good levels of internal consistency (α > 0.8) and convergent validity (r > 0.6). Discriminant validity cannot be established. Ratings for ease of use (3.6/5) and usefulness (3.4/5) were considered acceptable. Conclusions Further work is required to establish discriminant validity and refine the components and indicators. Once further refinement and validation are completed, the maturity model should be a simple tool for MDTs to measure their performance and monitor improvement over time.

The ability of optical evaluation to diagnose submucosal invasive cancer (SMIC) prior to endoscopic resection of large (≥20 mm) nonpedunculated colorectal polyps (LNPCPs) is critical to inform therapeutic decisions. Prior studies suggest that it is insufficiently accurate to detect SMIC. It is unknown whether lesion morphology influences optical evaluation performance.LNPCPs ≥20 mm referred for endoscopic resection within a prospective, multicenter, observational cohort were evaluated. Optical evaluation was performed prior to endoscopic resection with the optical prediction of SMIC based on established features (Kudo V pit pattern, depressed morphology, rigidity/fixation, ulceration). Optical evaluation performance outcomes were calculated. Outcomes were reported by dominant morphology: nodular (Paris 0-Is/0-IIa+Is) vs flat (Paris 0-IIa/0-IIb) morphology.From July 2013 to July 2019, 1583 LNPCPs (median size 35 [interquartile range, 25-50] mm; 855 flat, 728 nodular) were assessed. SMIC was identified in 146 (9.2%; 95% confidence interval [CI], 7.9%-10.8%). Overall sensitivity and specificity were 67.1% (95% CI, 59.2%-74.2%) and 95.1% (95% CI, 93.9%-96.1%), respectively. The overall SMIC miss rate was 3.0% (95% CI, 2.3%-4.0%). Significant differences in sensitivity (90.9% vs 52.7%), specificity (96.3% vs 93.7%), and SMIC miss rate (0.6% vs 5.9%) between flat and nodular LNPCPs were identified (all P.027). Multiple logistic regression identified size ≥40 mm (odds ratio [OR], 2.0; 95% CI, 1.0-3.8), rectosigmoid location (OR, 2.0; 95% CI, 1.1-3.7), and nodular morphology (OR, 7.2; 95% CI, 2.8-18.9) as predictors of missed SMIC (all P.039).Optical evaluation performance is dependent on lesion morphology. In the absence of features suggestive of SMIC, flat lesions can be presumed benign and be managed accordingly.

Background and Aims The endoscopic management of large nonpedunculated colorectal polyps involving the ileocecal valve (ICV-LNPCPs) remains challenging because of its unique anatomic features, with long-term outcomes inferior to LNPCPs not involving the ICV. We sought to evaluate the impact of technical innovations and advances in the EMR of ICV-LNPCPs. Methods The performance of EMR for ICV-LNPCPs was retrospectively evaluated in a prospective observational cohort of LNPCPs ≥20 mm. Efficacy was measured by clinical success (removal of all polypoid tissue during index EMR and avoidance of surgery) and recurrence at first surveillance colonoscopy. Accounting for the adoption of technical innovations, comparisons were made between an historical cohort (September 2008 to April 2016) and contemporary cohort (May 2016 to October 2020). Safety was evaluated by documenting the frequencies of intraprocedural bleeding, delayed bleeding, deep mural injury, and delayed perforation. Results Between September 2008 to October 2020, 142 ICV-LNPCPs were referred for EMR. Median ICV-LNPCP size was 35 mm (interquartile range, 25-50 mm). When comparing the contemporary (n = 66) and historical cohorts (n = 76) of ICV-LNPCPs, there were significant differences in clinical success (93.9% vs 77.6%, P = .006) and recurrence (4.6% vs 21.0%, P = .019). Conclusions With technical advances, ICV-LNPCPs can be effectively and safely managed by EMR, independent of lesion complexity. Most patients experience excellent outcomes and avoid surgery.

Obesity is a major public health burden. Outpatient clinics are an essential resource for individuals with obesity to access advice for weight loss management. The aim of this study was to compare anthropometric and weight loss outcomes between participants receiving general dietary (GD) advice, and those on a very low energy diet (VLED) under non-trial conditions. Data from 276 adults with obesity attending a multidisciplinary weight management clinic were analysed. Changes in anthropometry, body composition, and blood pressure (BP) over 12 months were analysed using linear mixed-effects models. Males on the GD demonstrated statistically greater reductions in body weight (BW), BMI, percent fat mass (FM), systolic BP, waist and hip circumference (p

A model to accommodate time-to-event ordinal outcomes was proposed by Berridge and Whitehead. Very few studies have adopted this approach, despite its appeal in incorporating several ordered categories of event outcome. More recently, there has been increased interest in utilizing recurrent events to analyze practical endpoints in the study of disease history and to help quantify the changing pattern of disease over time. For example, in studies of heart failure, the analysis of a single fatal event no longer provides sufficient clinical information to manage the disease. Similarly, the grade/frequency/severity of adverse events may be more important than simply prolonged survival in studies of toxic therapies in oncology. We propose an extension of the ordinal time-to-event model to allow for multiple/recurrent events in the case of marginal models (where all subjects are at risk for each recurrence, irrespective of whether they have experienced previous recurrences) and conditional models (subjects are at risk of a recurrence only if they have experienced a previous recurrence). These models rely on marginal and conditional estimates of the instantaneous baseline hazard and provide estimates of the probabilities of an event of each severity for each recurrence over time. We outline how confidence intervals for these probabilities can be constructed and illustrate how to fit these models and provide examples of the methods, together with an interpretation of the results.

Distinguishing between primary and secondary subtypes of membranous glomerulonephritis (MGN) is critical for its clinical management. We prospectively compared direct immunofluorescence (DIF) staining for phospholipase A

Right atrial (RA) and right ventricular (RV) parameters assessed by traditional echocardiography lack sensitivity to identify pulmonary embolism (PE). We sought to determine if alterations in RV free wall longitudinal strain (FWS) would be present in PE patients and improve evaluation. This retrospective study comprised of 84 consecutive PE patients from 2 centres, with adequate transthoracic echocardiography (TTE) images for RV FWS analysis. PE patients were compared to 66 healthy controls. Compared to controls, PE patients had increased RV parasternal long-axis diameter (RVPLAX) (33.4 ± 5.8 mm vs 39.9 ± 4.1 mm) and RA area (17.4 ± 5.6 cm2 vs 14.5 ± 3.1 cm2) (p

Background Pemphigus vulgaris (PV) is an autoimmune blistering disease driven by pathogenic antibodies to desmoglein-1 and -3, levels of which correlate with disease activity. Anti-desmoglein-3 IgG4 isotype antibodies are said to predominate in active disease and anti-desmoglein-3 IgG1 in remission; however, these observations arose from vertical studies, with limited assessments of clinical activity. The objective of this study was to examine the relationship between desmoglein autoantibodies, subdivided by isotype and disease activity using the validated PV activity tool "Pemphigus Disease Area Index (PDAI)." Methods Forty PV patients with predominantly mucosal disease were studied prospectively, 24 serially, and PDAI and anti-desmoglein antibodies recorded at each visit over a period of up to 15 months. Results At enrolment, only anti-desmoglein-3 IgG4 levels were significantly associated with disease activity but the correlation was weak. During follow-up, within-patient changes in disease activity correlated with changes in anti-desmoglein-3 IgG levels, but correlations were similar for both anti-desmoglein-3 IgG1 and IgG4. These trends were not observed in anti-desmoglein-1 IgG levels, although the majority of patients were negative at baseline. Conclusions Anti-desmoglein-3 IgG4 levels correlated only weakly with PDAI scores at a single time point. Reciprocity of IgG1 vs IgG4 anti-desmoglein-3 with changes in disease activity over time could not be confirmed, but rather, changes in levels of anti-desmoglein-3 IgG, irrespective of isotype, were useful in following individual patient responses.

Background and Aims Large sporadic duodenal adenomas are uncommon but they harbor malignant potential, which requires consideration of definitive treatment. EMR is gaining acceptance as an effective and safe alternative to high-risk surgical procedures, but data on long-term outcomes are limited. Herein we describe the short- and long-term outcomes of these lesions in a tertiary referral center. Methods Prospectively collected data were analyzed to identify risk factors for adverse events and outcomes. Patient demographics, lesion characteristics, and procedural technical data were collected. Results From 2007 to 2015, 106 adenomas ≥10 mm were resected (mean patient age, 69 years; 54% male; median size, 25 mm; interquartile range [IQR], 19–40). Complete endoscopic resection was achieved in 96%. Intraprocedural bleeding occurred in 43% of cases and was associated with lesion size ( P P = .003), and longer procedures ( P = .001). Delayed bleeding occurred in 15% (56% did not require active intervention) and was associated with lesion size ( P = .03). Perforation occurred in 3 patients. The 30-day mortality was 0%. Median follow-up was 22 months (IQR, 7–45). Histologically proven adenoma recurrence was identified and treated in 12 of 83 patients (14.4%) on first surveillance endoscopy. For the 53 patients for whom follow-up ≥12 months was available (median follow-up, 36 months; IQR, 24–51), 48 patients (90.6%) were free of adenoma and considered cured. Conclusions In a tertiary referral center, endoscopic resection of duodenal adenomas is a safe and effective alternative to surgery. Lesion size is strongly associated with adverse events, particularly intraprocedural bleeding and delayed bleeding. Good long-term outcomes are demonstrated.

Clinically significant bleeding (CSPEB) is the most frequent adverse event following wide-field endoscopic mucosal resection (WF-EMR) of large sessile and laterally spreading colorectal lesions (LSL). There is limited knowledge regarding accurate prediction of CSPEB. We aimed to derive a score to predict the risk of CSPEB.Data on patient and lesion characteristics and outcomes from WF-EMRs of LSL ≥20 mm at 8 referral hospitals were analyzed. The cohort was divided at random into equal sized training and test groups. Independent predictors of CSPEB in the training cohort were identified by multiple logistic regression analysis and used to develop a risk score. The performance of this score was assessed in the independent test cohort.Over 80 months to June 2015, 2,128 patients with 2,424 LSL were referred for WF-EMR. Two thousand and twelve patients were eligible for analysis. There were 135 cases of CSPEB (6.7%). In the training cohort of 1,006 patients, the independent predictors of CSPEB were lesion size30 mm (odds ratio (OR) 2.5), proximal colonic location (OR 2.3), presence of a major comorbidity (OR 1.5), and epinephrine in injection solution (OR 0.57). The derived risk score comprised lesion size30 mm (2 points), proximal colon (2 points), presence of major comorbidity (1 point), and absence of epinephrine use (1 point). The probabilities of CSPEB for scores of 0, 1, 2, 3, 4, and ≥5 in the training cohort were 1.5, 2.0, 5.6, 7.8, 9.1, and 17.5% and were 0.9, 6.7, 4.9, 6.2, 9.0, and 15.7% in the test cohort. The probabilities of CSPEB in those with low (score 0-1), medium (score 2-4), and elevated (score 5-6) risk levels were 1.7, 7.1, and 17.5% in the training cohort and 3.4, 6.2, and 15.7% in the test cohort.Patients at elevated risk of CSPEB can be identified using four readily available variables. This knowledge may improve the management of those undergoing WF-EMR and assist in designing studies evaluating CSPEB.

Extractable nuclear antigen (ENA) antibody testing is often requested in patients with suspected connective tissue diseases. Most laboratories in Australia use a two step process involving a high sensitivity screening assay followed by a high specificity confirmation test. Multiplexing technology with Addressable Laser Bead Immunoassay (e.g., FIDIS) offers simultaneous detection of multiple antibody specificities, allowing a single step screening and confirmation. We compared our current diagnostic laboratory testing algorithm [Organtec ELISA screen / Euroimmun line immunoassay (LIA) confirmation] and the FIDIS Connective Profile. A total of 529 samples (443 consecutive+86 known autoantibody positivity) were run through both algorithms, and 479 samples (90.5%) were concordant. The same autoantibody profile was detected in 100 samples (18.9%) and 379 were concordant negative samples (71.6%). The 50 discordant samples (9.5%) were subdivided into 'likely FIDIS or current method correct' or 'unresolved' based on ancillary data. 'Unresolved' samples (n = 25) were subclassified into 'potentially' versus 'potentially not' clinically significant based on the change to clinical interpretation. Only nine samples (1.7%) were deemed to be 'potentially clinically significant'. Overall, we found that the FIDIS Connective Profile ENA kit is non-inferior to the current ELISA screen/LIA characterisation. Reagent and capital costs may be limiting factors in using the FIDIS, but potential benefits include a single step analysis and simultaneous detection of dsDNA antibodies.

Objectives Perforation is the most serious complication associated with endoscopic mucosal resection (EMR). We propose a new classification for the appearance and integrity of the muscularis propria (MP) after EMR including various extents of deep mural injury (DMI). Risk factors for these injuries were analysed. Design Endoscopic images and histological specimens of consecutive patients undergoing EMR of colonic laterally spreading lesions ≥20 mm at a large Australian tertiary referral endoscopy unit were retrospectively analysed using our new DMI classification system. DMI was graded according to MP injury (I/II intact MP without/with fibrosis, III target sign, IV/V obvious transmural perforation without/with contamination). Histological specimens were examined for included MP and patient outcomes were recorded. All type III–V DMI signs were clipped if possible, types I and II DMI were clipped at the endoscopists’ discretion. Results EMR was performed in 911 lesions (mean size 37 mm) in 802 patients (male sex 51.4%, mean age 67 years). DMI signs were identified in 83 patients (10.3%). Type III–V DMI was identified in 24 patients (3.0%); clipping was successfully performed in all patients. A clinically significant perforation occurred in two patients (0.2%). Only one of the 59 type I/II cases experienced a delayed perforation. 85.5% of patients with DMI were discharged on the same day, all without sequelae. On multivariable analysis, type III–V DMI was associated with transverse colon location (OR 3.55, p=0.028), en bloc resection (OR 3.84, p=0.005) and high-grade dysplasia or submucosal invasive cancer (OR 2.97, p 0.014). Conclusions In this retrospective analysis, use of the new classification and management with clips appeared to be a safe approach. Advanced DMI types (III–V) occurred in 3.0% of patients and were associated with identifiable risk factors. Further prospective clinical studies should use this new classification. Trial registration number NCT01368289; results.

BACKGROUND Cardioembolism (CE) contributes to a large proportion of ischaemic stroke. AIMS To evaluate the demographic and clinical profile of CE stroke in Western Sydney. METHODS A retrospective analysis of ischaemic stroke patients presenting to Westmead Hospital (January-October 2016) was performed. Strokes were classified by TOAST (Trial of Org 10172 in Acute Stroke Treatment) criteria into different categories. Clinical and demographic data were collected on all stroke patients, and differences between CE and other stroke causes were identified. RESULTS Two hundred and twenty-eight consecutive patients (70.9 years; 53% male) were identified. By TOAST criteria, 21 (9%) had large-artery atherosclerosis, 94 (41%) CE, 10 (5%) small-vessel disease, 2 (1%) other aetiology and 101 (44%) undetermined aetiology. A significant proportion of CE stroke patients had cardiovascular risk factors including hypertension (66%), hypercholesterolaemia (50%), diabetes (26%) and ischaemic heart disease (28%). The majority (81%) of patients with CE had atrial flutter/flutter. CE stroke, compared with other types of stroke, was more common in females (56 vs 41%, P = 0.022) and patients with CE stroke were more likely to have previous cerebral ischaemia (34 vs 21%, P = 0.026), suggesting increased recurrence in this group. Of the patients with atrial flutter/flutter (n = 56), the majority (87%) had a high CHA2 DS2 -VASC score (≥2); however, a significant proportion (55.4%) were not on anticoagulation. CONCLUSIONS Cardioembolic stroke remains a significant burden in Western Sydney, and it is likely that a significant proportion may be preventable, as evidenced by the substantial presence of modifiable cardiovascular risk factors, and inadequate anticoagulation of patients with atrial arrhythmias.

Pulmonary embolism (PE) is associated with a high mortality; whether echocardiographic evaluation at presentation predicts long-term adverse outcomes is of importance. We sought to determine if a composite of routinely obtained echocardiographic parameters could determine long-term adverse events in PE patients. Right ventricular (RV) size and function and right atrial (RA) size were retrospectively evaluated in 233 consecutive PE patients with an inpatient echocardiogram, and compared with 70 healthy controls; mortality at 3 years was confirmed. PE patients had increased RV size (RV parasternal long-axis diameter [RVPLAX] and RV end-diastolic volume [p0.001 for both]) and RA area (p0.001). RV function was reduced in PE patients (RV fractional area change and RV ejection fraction [p0.001 for both]). Peak tricuspid regurgitation (TR) velocity was higher in the PE group. At follow-up (3.0 ± 2.1 years), 61 patients died; multivariable analysis demonstrated RVPLAX diameter37 mm (hazard ratio [HR] 2.3, 95% confidence interval [CI] 1.3 to 4.2; p = 0.005), RA area20 cm

BACKGROUND AND PURPOSE Ischaemic stroke frequently has a cardioembolic (CE) source. Clinical and echocardiographic parameters associated with CE stroke were evaluated. METHODS In all, 93 consecutive ischaemic stroke patients who underwent a transthoracic echocardiogram were retrospectively analysed; strokes were classified by TOAST (Trial of Org 10172 in Acute Stroke Treatment) criteria. Echocardiographic parameters related to CE stroke, including left atrial volumes and function, were compared to 73 healthy controls. RESULTS Of 93 patients (mean age 66.1 years, 56% male), nine (10%) had large artery atherosclerosis, 38 (41%) CE stroke, two (2%) small vessel disease, two (2%) other and 42 (45%) undetermined aetiology. Left atrial (LA) maximum volumes (LAVImax ) and minimum volumes (LAVImin ) were larger in the CE group than the non-CE group (45 vs. 32 ml/m2 , 32 vs. 13 ml/m2 , respectively, P

To date, cutaneous toxicities of combination therapies of anti-programmed death-1 (anti-PD1) and ipilimumab are poorly described. Understanding cutaneous presentations will aid clinicians with early diagnoses and treatments. We aim to describe and compare the cutaneous toxicities between the combination therapies and anti-PD1 monotherapy. This is a cohort study comparing previously published data on 82 patients with metastatic melanoma on anti-PD1 monotherapy, with a new group of 25 patients with metastatic melanoma receiving combined ipilimumab and pembrolizumab between January 2015 to February 2016. A single institution, internal referrals were received from medical oncology teams from May 2012 to February 2015 for the anti-PD1 monotherapy group and from January 2015 to February 2016 for combination group. All patients who were treated with either anti-PD1 therapy or combination therapies during the timeframe within the institution were included in the study. Kaplan-Meier curves were used to illustrate the time taken to develop cutaneous toxicities in the monotherapy and combination groups. Of the 25 patients, 88% developed new cutaneous lesions since the treatment. Immune-related lesions; lichenoid reaction (64%) and vitiligo (28%) were the most frequent. The incidence of lichenoid reaction increased rapidly in the early phase of treatment. Approximately one-third developed their first lichenoid reaction within 12 days of commencing treatment in combination group compared to 14 months in the anti-PD1 monotherapy. The rate of incidence of vitiligo was comparable in both groups. There was no statistical significance in the development of cutaneous toxicities and the treatment response between the two groups. The time taken to develop immune-related cutaneous toxicities was shorter for those on combination therapy versus anti-PD1 monotherapy.

Application of medicated honey (MH) to peritoneal dialysis (PD) catheter exit sites has been found to be as effective as intra-nasal mupirocin for preventing PD catheter-related infections (CRIs), but was associated with increased risk for CRIs in diabetics. The efficacy of topical MH as a prophylactic agent has not been compared with the exit-site application of povidone iodine (PI). This retrospective multicentre cohort study compared cumulative incidence rates of PD CRIs (peritonitis or exit-site infections) and the number of PD CRIs observed per patient over the study period with PD exit-site application of MH or PI, in both diabetic and non-diabetic patients. Outcomes were compared in incident patients in 2 eras: January 2011 – December 2012, when 147 received exit-site care with PI (PI group), and July 2013 – June 2015, when 171 patients applied MH (MH group). Patients were followed until technique failure, death, transplant, or end of study treatment era. Cumulative incidence of PD CRIs was higher in the PI group (hazard ratio [HR] = 1.7, 95% confidence interval [CI] 1.1 – 2.6, p = 0.019) and the benefit of MH was not modified by diabetic status (present/absent, interaction p = 0.723). A similar trend was observed in the cumulative incidence of peritonitis (HR = 1.6, 95% CI 0.99 – 2.6, p = 0.059). After adjusting for months of exposure, the rate ratio for PD CRIs was 1.58 for PI compared to MH (95% CI, 1.03 – 2.42, p = 0.035). We conclude that exit-site application of MH is more effective than PI in preventing PD CRIs, and this effect is not modified by the presence or absence of diabetes.

Colorectal cancer (CRC) can be prevented by colonoscopy and polypectomy. Endoscopic mucosal resection (EMR) is performed to remove large laterally spreading colonic lesions that have a high risk of progression to CRC. Endoscopically invisible micro-adenomas at the margins of the EMR site might contribute to adenoma recurrence, which occurs in 15% to 30% of patients who undergo surveillance. We aimed to determine the efficacy of adjuvant thermal ablation of the EMR mucosal defect margin in reducing polyp recurrence.We performed a prospective study of 390 patients with large laterally spreading colonic lesions (≥ 20 mm, n = 416) referred for EMR at 4 tertiary centers in Australia. After complete lesion excision by EMR, lesions were randomly assigned to thermal ablation of the post-EMR mucosal defect margin (n = 210) or no additional treatment (controls, n = 206). We performed surveillance colonoscopies with standardized photo documentation and biopsies of the scar after 5 to 6 months. Patient, procedure, and lesion characteristics were similar between the groups. The primary endpoint was detection of lesion recurrence at first surveillance colonoscopy.A significantly lower proportion of patients who received thermal ablation of the post-EMR mucosal defect margin had evidence of recurrence at first surveillance colonoscopy (10/192, 5.2%) than controls (37/176, 21.0%) (P .001). The relative risk of recurrence in the thermal ablation group was 0.25 compared with the control group (95% confidence interval 0.13-0.48). Rates of adverse events were similar between the groups.In a multicenter randomized trial, thermal ablation of the post-EMR mucosal defect margin significantly reduced polyp recurrence at first surveillance colonoscopy, compared with no additional treatment. Routine implementation of this simple and safe technique could increase the utility of EMR, decrease surveillance burdens, and reduce morbidity and mortality from CRC. ClinicalTrials.gov no: NCT01789749.

Background The cytomorphological features in the distinction between phyllodes tumour (PT) and fibroadenoma (FA) on fine needle aspiration biopsy (FNAB) remains challenging because of the biphasic nature of these lesions and the rarity of PT. Methods FNAB smears of histologically confirmed PT (N = 26) and FA (N = 78) cases were retrieved from a retrospective database interrogation from the Department of Cytology/Tissue Pathology, ICPMR Pathology West (Cerner Millennium) in Westmead Hospital. For each case, two smears were selected, de-identified and independently reviewed by four observers comprising two cytologists and two cytopathologists. Cytological parameters examined included detailed evaluation of smear cellularity, epithelial and stromal components as well as the smear background. Results The cytological features of moderate to marked stromal cellularity and stromal nuclear atypia were more evident in PT than in FA, identified by three out of four observers. The epithelial characteristics, presence of macrophages, multinucleated giant cells and blood vessels showed no statistically significant differences in the distinction between the two lesions. Conclusion The results of this study indicate that in all of the cytological features assessed for PT and FA, no single cytological feature was found to be statistically significant in identifying PT across all observers. This reflects the overlap of cytological features seen in these lesions. FNAB cytology cannot reliably distinguish FA and PT.