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Background/Aim: Matrix metalloproteinase 13 (MMP13) has been reported to be involved in tumor development and progression, including of colorectal cancer (CRC). This study aimed at evaluating whether the MMP13 rs2252070 gene polymorphism is associated with clinicopathological factors and its influence on long-term survival in Swedish patients with CRC. Patients and Methods: A total of 723 patients with CRC were genotyped using TaqMan single nucleotide polymorphism assays based on polymerase chain reaction. Results: Assessing clinicopathological factors, we demonstrated that having the G/G genotype for MMP13 rs2252070 was significantly associated with poor differentiation, higher serum level of carcinoembryonic antigen and higher lymph node status. Moreover, the presence of a G allele was significantly related to larger tumor size in rectal cancer but had a significantly protective role against mucinous cancer, perineural invasion and lymphovascular invasion. Kaplan-Meier analysis showed no difference between genotypes regarding cancer-specific survival. Conclusion: Our findings highlight the potential of MMP13 rs2252070 polymorphism as a useful predictor of poor differentiation, serum level of carcinoembryonic antigen, lymph node status, tumor size, mucinous cancer, perineural invasion and lymphovascular invasion in patients with CRC.

Background: Identifying people at risk of poor outcomes following treatment for substance use disorders is important for developing tailored services. The aim of this study was to test whether a brief measure of internalizing and externalizing behavior could identify young adults at high risk of psychiatric care episodes and criminal offending up to four years after enrolment in treatment for substance use disorder. Methods: Clients aged 15–25 years from a randomized multicenter study were included (N = 457). At baseline, all completed the YouthMap12 screener, a measure of internalizing symptoms (IP6) and externalizing problems (EP6). We used accelerated failure time regression to assess time to psychiatric care and criminal offending, adjusting for baseline occurrence, gender, age, treatment group, and uptake area. Youden's J was used to assess optimal cut-points for risk of events. Results: The IP6 was associated with shorter time to psychiatric care following treatment enrolment (beta = −0.71, 95% confidence interval [CI] = −0.94 to −0.48; adjusted beta = −0.45, 95% CI = −0.66 to −0.25). The EP6 was associated with shorter time to criminal offending, coefficient = −0.32, 95% CI = −0.44 to −0.19; adjusted coefficient = −0.18, 95% CI = −0.30 to −0.06). Optimal cut-points were two or more for the IP6 and three or more for the EP6. Conclusions: The IP6 and the EP6, two simple and easily administered instruments, can identify young adults who are at an increased risk of future criminal offending or in need of psychiatric care. The findings lend support to using the 12-item YouthMap, as it identifies relevant risks, is compatible with local service delivery needs, and is theoretically and empirically supported. © 2022 The Author(s)

Background and Aims: Hepatic hydrothorax (HH) is an uncommon and difficult-to-manage complication of cirrhosis with no established clinical guidelines. We sought to define the clinical outcomes of patients presenting with HH managed with current standards-of-care. Method(s): International Classification of Diseases-10 codes identified cirrhotic patients with HH presenting to 3 tertiary centres (Melbourne, Australia) from 2010 to 2018. HH was defined as pleural effusion in the absence of cardiopulmonary disease. Medical records were reviewed to determine baseline characteristics and survival. Primary outcome was 12-month mortality. The Kaplan-Meier method was used to calculate survival probability. Result(s): 83 patients were included. Median age was 59 years (IQR 54-63), 57% were male and median MELD score was 29 (IQR 25-33). Common causes of cirrhosis were viral (33%), alcohol (27%) and nonalcoholic fatty liver disease (19%); 29% had hepatocellular carcinoma. Pleural effusions were typically right-sided (83%) and 73% had concurrent ascites. There were 169 hospital admissions for HH over the study period. Median length of stay was 11 days and 22% required intensive care unit admission. 89% and 7% patients were prescribed diuretics and non-selective beta-blockers respectively at presentation. Diuretic therapy alone was commenced in 13 (8%) presentations while 120 (71%) received diuresis and pleurocentesis (median 3L drained); 17% required blood products to facilitate pleurocentesis. 23 patients received intercostal drain insertion, 1 pleurodesis and 10 proceeded to transjugular intrahepatic portosystemic shunt insertion. 31 (37%) patients underwent liver transplantation (OLT). Significant complications were observed in 45% of admissions, including: infection [n = 25], hepatic encephalopathy [n = 19] and pneumothorax [n = 11]. 86% patients required re-admission within 6-months of index admission. The 12-month mortality rate was 29% (n = 24) and probability of transpla

Aim: To describe the impact of initial steroid sensitivity on risk of disease recurrence and transplant failure for children following kidney transplantation for steroid resistant nephrotic syndrome (SRNS). Background(s): Scarce prior data suggest that children transplanted for SRNS who were steroid responsive at their initial presentation have an increased risk of recurrence post transplantation. There are no data informing the impact of initial steroid sensitivity on transplant survival. Method(s): Children who received a kidney transplant between 2000 and 2019 for SRNS in 7 paediatric centres were included. Clinical data were gathered from chart reviews and transplant data were provided from ANZDATA following ethics approval. Transplant survival was estimated using the Kaplan-Meier estimator, and the association between variables and graft survival estimated by Cox modelling. Result(s): There were 56 children, 32 (57%) male, average age at transplant 11 years (SD 4) and 36 (65%) Caucasian. At presentation, 19/56 (34%) were steroid sensitive before developing SRNS. Of those steroid sensitive initially, 18/19 (95%) had recurrence post-transplant, 9/18 (50%) achieved full remission, although 3 of these had further recurrences. In those not steroid sensitive initially, 14/37 (38%) had recurrence post-transplant, 7/14 (50%) achieved full remission although one had further recurrences. Overall, 5-year transplant survival was 72% (95%CI = 60-86%) and initial steroid sensitivity was not significantly associated with transplant loss (p = 0.07). Conclusion(s): Initial steroid sensitivity is strongly associated with SRNS recurrence. Transplant survival for children with SRNS is poor. Further research in other cohorts is needed to assess if initial steroid sensitivity is associated with poorer graft outcomes.

Objective: To describe the clinical characteristics and outcomes of systemic sclerosis-mixed connective tissue disease (SSc-MCTD) and SSc overlap syndrome. Method(s): We included patients from the Australian Scleroderma Cohort Study who met American College of Rheumatology/European Alliance of Associations for Rheumatology criteria for SSc. Three mutually exclusive groups were created: SSc-MCTD, SSc overlap, and SSc only. Univariate comparison of clinical features was performed by analysis of variance or chi-square test. Survival analysis was performed using Kaplan-Meier (KM) curves and Cox proportional hazards regression models. Result(s): Of 1,728 patients, 97 (5.6%) had SSc-MCTD, and 126 (7.3%) had SSc overlap. Those with MCTD-SSc were more commonly Asian (18.3% versus 10.1% in SSc overlap, and 3.6% in SSc only; P < 0.0001) and younger at disease onset (38.4 years versus 46.5 or 46.8 years, P < 0.0001). Those with SSc-MCTD or SSc overlap were more likely to have limited cutaneous SSc. All 3 groups had similar frequency of interstitial lung disease (ILD), although pulmonary arterial hypertension (PAH) was less common in SSc overlap. Synovitis and myositis were more common in SSc overlap and SSc-MCTD than in SSc only. KM curves showed better survival in SSc-MCTD than SSc overlap or SSc only (P = 0.011), but this was not significant after adjustment for sex and age at disease onset. SSc-specific antibodies were survival prognostic markers, with antinuclear antibody centromere or anti-RNP conferring better survival than anti-Scl-70 or anti-RNA polymerase III (P = 0.005). Patients with SSc-MCTD and SSc overlap had lower mortality following diagnosis of ILD and PAH than patients with SSc only. Conclusion(s): This study provides insights into the clinical characteristics of patients with SSc-MCTD, SSc overlap, and SSc only and shows that anti-RNP antibodies are associated with better survival than anti-Scl-70 and anti-RNA polymerase III antibodies.Copyright © 2020, Amer

Background and Aim: Hepatic hydrothorax (HH) is an uncommon and difficult-to-manage complication of cirrhosis, with no established clinical guidelines.We sought to define the clinical outcomes of patients presenting with HH and managed with current standards of care. Method(s): ICD-10 codes identified cirrhotic patients with HH presenting to three tertiary centers in Melbourne, Australia, from 2010 to 2018. HH was defined as pleural effusion in the absence of cardiopulmonary disease. Medical records were reviewed to determine baseline characteristics and survival. The primary outcome was 12-month mortality. The Kaplan- Meier method was used to calculate survival probability. Result(s): A total of 82 patients were included (median age, 59 years [IQR, 54-63]; 56% male; median Model for End-Stage Liver Disease score, 29 [IQR, 25-33]). Common causes of cirrhosis were viral (33%), non-alcoholic fatty liver disease (19%), and alcohol (16%); 29% of patients had hepatocellular carcinoma. Pleural effusions were typically right-sided (85%), and 73% had concurrent ascites. There were 169 hospital admissions for HH during the study period. Mean length of stay was 12 days, and 27% required intensive care unit admission. At presentation, 89% and 7% of patients were prescribed diuretics and non-selective betablockers, respectively. Diuretic therapy alone was commenced in 13 presentations (8%), while 120 patients (71%) received diuresis and pleurocentesis (median, 3 L drained); 25% required blood products to facilitate pleurocentesis. Twenty-three patients received intercostal drain insertion, one had pleurodesis, and 10 proceeded to transjugular intrahepatic portosystemic shunt insertion. There were 24 patients (29%) who underwent orthotopic liver transplantation (OLT). Significant complications were observed in 46% of admissions, including acute kidney injury (n = 54), infection (n = 28), hepatic encephalopathy (n = 21), and pneumothorax (n = 11). Overall, 83% of patients require

Introduction: Immune checkpoint inhibitors (ICIs) have improved outcomes of patients with advanced non-small cell carcinoma (NSCLC). There is no consensus on the maximum duration of ICIs in metastatic disease. Immune related adverse events (IRAEs) with ICIs, although rare, can have serious and life-long consequences. We aim to describe the real-world data on outcomes of NSCLC patients who stopped ICIs earlier than proposed duration due to IRAEs. Method(s): Patients with stage III or IV NSCLC treated with ICIs at Monash Health (Melbourne, Australia) from 2015 to 2019 were retrospectively reviewed. Patients enrolled to clinical trials were excluded. Baseline clinicopathological factors and anti-cancer treatment details were collected. Immunohistochemistry for PD-L1 staining was performed and scored according to standardised practice. IRAEs and reason for ICI cessation was recorded. Overall survival (OS) from the start of ICI was calculated using Kaplan-Meier method. Result(s): A total of 148 patients received ICI therapy with 97 male (66%) and 51 female (34%) patients. 91% were smokers and ECOG 0 or 1 was found in 95%. PD-L1 expression was known in 53/148 patients; where 19% were scored as low, 43% as intermediate and 20% as high. Stage at commencement of ICI was III in 36/148 (24%), where 32/36 (89%) received adjuvant durvalumab after curative intent chemoradiotherapy, and metastatic in 112/148 (76%), where 99 (88%) received nivolumab and 13 (12%) received pembrolizumab, after first line chemotherapy. Median doses of ICIs were 17 in stage III, and 7 in stage IV cohorts. ICIs were ceased in 93/148 (63%) cases due to disease progression, while 38/148 (26%) stopped due to IRAEs; 17 (12%) in stage III and 21 (14%) in stage IV cohort. Severe IRAEs (grade 3 or higher) were pneumonitis (7/148, 5%), colitis (4/148, 3%), endocrinopathy (2/148, 1%), arthritis (2/148, 1%), rash (2/148, 1%) cardiac (2/148, 1%), liver (1/148, 1%), optic neuritis (1/148, 1%), thrombocytopenia (1/1

E/D163 polymorphism of dog prion protein (PrP) has been recently proposed as the variant responsible for canid prion resistance. To further investigate the protective role of this variant against prion replication, the transgenic mouse model OvPrP-Tg532 expressing sheep/goat PrP carrying the substitution D162 (equivalent to D163 position of dog PrP) was generated and intracranially inoculated with a broad collection of small ruminant prion strains. OvPrP-Tg532 mice showed resistance to classical bovine spongiform encephalopathy (BSE) from sheep and some classical scrapie isolates from sheep and goat but were susceptible to ovine atypical L-BSE and numerous classical scrapie isolates. Strikingly, some of these classical scrapie isolates showed a shift in their prion strain properties. These results suggest that other PrP residues apart from E/D163 variant of dog PrP or factors distinct than PrP may participate in prion resistance of canids and that different factors may be required for D162 sheep PrP to provide effective protection to sheep against ruminant prions.

Background: DN is the most common cause of ESKD among patients with T2DM, however there is growing evidence that T2DM patients with non-DN as a cause of ESKD form a distinct clinical entity with differential prognostic significance Methods: All incident ESKD patients initiated on hemodialysis/peritoneal dialysis in Australia and New Zealand between 1980-2014 were included, using data from the ANZDATA Registry. The association between diabetes status at dialysis initiation (i.e. no diabetes, T2DM+DN or T2DM+non-DN) and mortality were examined using Cox regression and competing risk analyses, with transplantation censored or considered as competing risk, respectively Results: Of 56,552 incident dialysis patients followed for a median of 2.5 years, 15,829 (28%) and 4993 (9%) had T2DM+DN and T2DM+non-DN, respectively. Patients with T2DM were significantly older and a greater proportion had vascular comorbidities. Compared to patients with no diabetes, the adjusted HR (95%CI) for mortality in those with T2DM+DN and T2DM+non-DN were 1.39 (1.35-1.43) and 1.24 (1.29-1.29) in the Cox regression model, and the adjusted subdistribution HR were 1.52 (1.47-1.56) and 1.32 (1.27-1.38), respectively in the competing risk model. There was a significant interaction (p<0.001) between age and diabetes status, with the hazard for mortality greater in younger compared to older patients. Cardiovascular disease as a cause of mortality was more common in patients with T2DM compared to no diabetes (43% vs. 34%, p<0.001). Kaplan Meier survival curves for mortality stratified by age categories are shown below Conclusion(s): Younger ESKD diabetic patients with or without DN experienced substantially poorer survival compared to non-diabetic patients. A vigilant approach to CVD prevention and monitoring is critical to improve clinical outcomes in diabetic patients with ESKD.

Background: The androgen receptor (AR) remains a critical driver in metastatic castration-resistant prostate cancer (mCRPC). Profiling AR aberrations in both circulating DNA and RNA may identify key predictive and/or prognostic biomarkers in the context of contemporary systemic therapy. Objective(s): To profile AR aberrations in circulating nucleic acids and correlate with clinical outcomes. Design, setting, and participants: We prospectively enrolled 67 mCRPC patients commencing AR pathway inhibitors (ARPIs; n = 41) or taxane chemotherapy (n = 26). Using a first-in-class next-generation sequencing-based assay, we performed integrated cell-free DNA (cfDNA) and cell-free RNA (cfRNA) profiling from a single 10 ml blood tube. Outcome measurements and statistical analysis: Kaplan-Meier survival estimates and multivariable Cox regression analyses were used to assess associations between clinical outcomes and the following AR aberrations: copy number variation, splice variants (AR-V7 and AR-V9) and somatic mutations. Results and limitations: Cell-free DNA and cfRNA were successfully sequenced in 67 (100%) and 59 (88%) patients, respectively. Thirty-six (54%) patients had one or more AR aberrations. AR gain and cumulative number of AR aberrations were independently associated with clinical/radiographic progression-free survival (PFS; hazard ratio [HR] 3.2, p = 0.01 and HR 3.0 for 0 vs >=2, p = 0.04) and overall survival (HR 2.8, p = 0.04 and HR 2.9 for 0 vs >=2, p = 0.03). Notably, concurrent AR gain and AR splice variant expression (AR gain/AR-V+) was associated with shorter prostate-specific antigen PFS on both ARPIs (HR 6.7, p = 0.009) and chemotherapy (HR 3.9, p = 0.04). Importantly, key findings were validated in an independent cohort of mCRPC patients (n = 40), including shorter OS in AR gain/AR-V+ disease (HR 3.3, p = 0.02). Limitations include sample size and follow-up period. Conclusion(s): We demonstrate the utility of a novel, multianalyte liquid biopsy assay ca

Background: Multiple tumour tissue studies have demonstrated the prognostic utility of CNVs in mCRPC. However, accurate assessment of CNVs in plasma cfDNA remains challenging, and prognostic significance has not been well characterized. Using a large customized panel, we correlated plasma CNVs with clinical outcomes in a contemporary cohort of mCRPC patients. Method(s): Deep targeted sequencing was performed using a 180-gene cfDNA panel (Predicine) in 56 patients commencing AR pathway inhibitors (enzalutamide or abiraterone; n = 34) or taxane chemotherapy (n = 22) at two Australian institutions. Kaplan-Meier estimates and Cox proportional-hazards models were used to correlate CNVs with progression-free survival (PFS) and overall survival (OS). Significant results were validated in an independent cohort (Mayo Clinic, n = 144). Result(s): Median follow-up was 19.4 months (mo; IQR 11.3-31.9). The most common CNVs in the Australian cohort are shown (Table). OS was significantly decreased in patients with PI3KCA gain (median 21.7 mo vs 6.6 mo, p < 0.0001 ), PTEN loss (24.8 mo vs 11.7 mo, p = 0.0019) and AR gain (21.7 mo vs 12.0 mo, p = 0.0083). Furthermore, all three alterations independently predicted for poor survival in multivariable analyses (MVA; Table). Findings in the independent cohort showed similar OS results in MVA: PIK3CA gain (HR 2.0, p = 0.07), PTEN loss (HR 1.7, p = 0.08) and AR gain (HR 1.7, p = 0.03). Conclusion(s): Sequencing of plasma cfDNA revealed that PTEN loss, and PIK3CA and AR gain are associated with inferior clinical outcomes in patients commencing contemporary systemic treatment. These data support therapeutic strategies co-targeting the PI3K and AR pathways in mCRPC. Covariates in MVA: circulating tumour DNA fraction > 2%, prior treatment, visceral disease, baseline pain and ECOG >2.

Background: Elderly men (>/=75yo) comprise 25% of patients with prostate cancer. However, they are typically underrepresented in pivotal trials. Limited data suggest these patients receive less intensive treatment with greater toxicity, despite comparable response rates. Our retrospective study examined treatment patterns and outcomes in a real-world population with castration-resistant prostate cancer (CRPC). Method(s): Using the multi-centre electronic CRPC Australian Database (ePAD), we extracted clinicopathologic, treatment and outcome data. Descriptive statistics were used to report data in patients aged >/=75yo and <75yo. Comparisons between these groups were analysed using T-tests and Fisher's exact tests. Time-to-event analyses were performed using the Kaplan-Meier method. Result(s): We identified 753 men with CRPC, with 327 (43%) aged >/=75yo. Elderly patients had higher rates of ischemic heart disease (33% vs 16% in younger patients, p=0.004) and stroke (11% vs 5%, p=0.007). They were more likely to receive only one line of systemic therapy (67% vs 40%, p<0.001), and androgen receptor signalling inhibitors (ARSIs) were most commonly prescribed as initial therapy (78% vs 48%, p<0.001). Enrolment in clinical trials was less frequent (5% vs 15%, p<0.001). There was no statistical difference in treatment duration or PSA50 response rates with ARSIs or docetaxel (Table). Overall, serious adverse events (SAEs) leading to hospitalisation, dose delays or modifications occurred in more elderly men (24% vs 16%, p=0.003), with a trend towards greater SAEs in those receiving docetaxel or ARSIs. Elderly patients were more likely to stop docetaxel due to toxicity (39% vs 21%, p=0.02). [Formula presented]. Conclusion(s): In our real-world cohort, elderly men had greater comorbidities and received fewer lines of systemic therapy. Although there was no difference in treatment response or duration, elderly patients experienced higher SAE rates. Prospective studies are requir

Background: Preclinical studies have shown potential synergism from blocking both programmed cell death protein-1 (PD-1) and programmed death-ligand 1 (PD-L1). BGB-A333 is an investigational humanized monoclonal antibody against PD-L1 that has antitumor activity in xenograft models. Tislelizumab, a clinical-stage anti-PD-1 antibody, showed clinical activity in patients (pts) with advanced solid tumors. We report results from the expansion cohort (phase IIB) of an open-label phase I/II study (NCT03379259) of BGB-A333 plus tislelizumab in pts with previously treated advanced urothelial carcinoma (UC). Method(s): Patients received BGB-A333 1350 mg IV Q3W + tislelizumab 200 mg IV Q3W. Eligible pts had locally advanced or metastatic UC without prior PD-(L)1 therapy, could not tolerate or progressed during/after treatment with platinum-based chemotherapy, and had an ECOG performance status of <=1. The primary endpoint was investigator-assessed objective response rate (ORR) per RECIST v1.1. Key secondary endpoints included duration of response (DoR) per RECIST v1.1, progression-free survival (PFS) estimated with Kaplan-Meier analysis, and the safety/tolerability profile evaluated by monitoring adverse events (AEs). Result(s): As of 10 March 2020, 12 pts (median age, 69.5 yr; 92% male) with UC were enrolled; median study follow-up, 8.3 mo. Most pts (n=10, 83%) had 1 prior systemic therapy. Median duration of treatment for both BGB-A333 and tislelizumab was 5.5 mo (range: 1.2, 9.9). Confirmed ORR was 42% (95% CI: 15.2, 72.3); 3 pts had complete responses, 2 had partial responses, 4 had stable disease (SD; 2 had SD >6 mo), 2 had progressive disease, and 1 was not evaluable (due to missing postbaseline assessment). Median DoR was not reached; median PFS was 6.1 mo (95% CI: 1.9, not estimable). Across the entire study (n=39), treatment-related AEs (TRAEs) occurred in 19 pts. Of the 24 pts receiving combination treatment, four pts (including one with UC) had grade >=3 TRAEs. One

Purpose: Since the introduction of the Biotronik Linox S/SD leads in 2006, there have been multiple reports of premature lead failure. The purpose of this study was to investigate the longevity of the Linox S/SD leads and to identify the possible predictors of lead failure in a single tertiary implant center. Method(s): We retrospectively reviewed patients who underwent implantation of Linox S/SD leads or Sorin Vigila 1CR/2CR leads (the same Linox S/SD leads marketed by Sorin) at our center. The cumulative lead survival was estimated using the Kaplan-Meier curve, and variables associated with lead failure were assessed by Cox proportional hazard model. Result(s): A total of 187 patients (154 (82%) male) underwent Linox S/SD or Vigila 1CR/2CR implantation between 2007 and 2013. During follow-up with a median time of 75 months, nine lead failures were identified (4.8%). The mean and median times from lead implantation to lead failure were 70.7 +/- 21 months and 64 (45-111) months, respectively. The cumulative survival probability for the Linox S/SD at 5 years was 97.1% and at 12 years was 90.3%. Non-physiological high-rate sensing was the most common type of lead failure in patients. In two-thirds of these patients, this led to inappropriate shock. We did not find any significant relationships between patients' clinical and procedural characteristics and lead failure. Conclusion(s): At our center, the 5-year lead survival of the Linox S/SD has been better than reports from other centers. The majority of lead failures presented as non-physiological high-rate sensing with subsequent inappropriate therapy.Copyright © 2020, Springer Science+Business Media, LLC, part of Springer Nature.

BACKGROUND: Histologic transformation (HT) is an important event with adverse prognosis in the natural history of indolent lymphomas. There is minimal data on HT in the Australian setting. AIM: To characterise patients with biopsy-proven HT and their outcomes identified at a tertiary Australian Hospital. METHOD(S): All patients with biopsy-proven HT during a 15-year period (2002-2017) were included. Clinico-pathological data were systematically collected from review of patient records. Survival estimates were assessed by the Kaplan-Meier method and compared using the log-rank test. Associations between variables and clinical outcomes were evaluated using Cox's proportional hazards model. RESULT(S): A cohort of 45 patients was identified with a median age of 66years and the majority (59%) having high-risk disease (Revised-International Prognostic Index score >=3). R-CHOP induction was used in 69% with an overall response rate of 82% (complete response (CR), 75%). 61% of these induction-responders received consolidation, with autologous stem cell transplant (ASCT) performed in only 17% and rituximab maintenance given to 31%. With a median follow-up of 47 months (range: 4-136), the 5-year overall survival (OS) was 69% (95% CI: 52%, 81%). Chemotherapy-naivety at HT was associated with a superior rate of CR (84% vs. 54%, p = 0.057) and 5-year OS (82% vs. 46%, p = 0.012). Rituximab maintenance was associated with a durable progression-free survival in induction-responders. CONCLUSION(S): Excellent OS was observed in this modern cohort of patients treated with rituximab-containing induction and low rate of consolidation by ASCT, particularly in those who were chemotherapy-naive at HT. This article is protected by copyright. All rights reserved.

Background: Grade 3B Follicular lymphoma (G3BFL) comprises approximately 15% of FL and controversy exists over whether it follows the relapsing/remitting course of low-grade FL, or more closely resembles diffuse large B cell lymphoma (DLBCL), which is potentially curable. Thus it is largely excluded from clinical trials for either group, hence robust data and management consensus are lacking. Aim(s): To establish survival outcomes of G3BFL. Method(s): We performed an international retrospective study of patients aged > / = 18 years, with G3BFL from tertiary institutions in Australia, Canada and England. Pure G3B, composite Grade 3A/G3BFL and G3BFL/ DLBCL treated with rituximab (R) or obinutuzumab (O) + chemotherapy +/- radiotherapy (RT) or RT alone between 2002-2019 were included. FL grading was according to WHO criteria. A comparator DLBCL group, treated with R-CHOP +/- radiotherapy from 2012-2018 was identified using the same criteria from 2 Australian sites. OS was defined as the time from the date of diagnosis until death from any cause; PFS was defined from diagnosis until relapse/progression (to any B cell lymphoma subtype) or death; both were calculated according to the Kaplan-Meier method. Associations between prognostic factors and outcomes were analysed with log-rank tests and Cox proportional hazards models. Result(s): 161 G3BFL cases were evaluable. Histology was G3BFL in 84, G3A/G3B FL in 25, and G3B/DLBCL in 52 ("G3B" group). Median age was 62 (18-86) and 55% were male. 71% of patients had stage III/ IV disease. 58% had a high FLIPI score. Treatment was R or O-CHOPlike chemotherapy +/- RT in 96% of cases with RT alone or BR in the remainder (2% each). 90% received anthracyclines. 171 DLBCL comparator cases were included with a median age of 68 years (25-91) and a high R-IPI in 54%. Compared to the G3B group, there was a statistically significant difference in age > 60 years (G3B: 53%, DLBCL 71%; P = 0.001), ECOG performance status > 2 (G3B 5%, DLBCL 23

Background: Mixed connective tissue disease (MCTD) is defined by presence of anti-RNP antibody together with specific clinical features. Patients who fulfil diagnosis of SSc and have features of other connective tissue diseases are often classified as SSc-overlap. Our study aims to describe the clinical characteristics and outcomes of SSc-MCTD and SScoverlap. Method(s): We included patients from the Australian Scleroderma Cohort Study (ASCS) who met ACR/EULAR diagnostic criteria for SSc. Three mutually exclusive groups were created: SSc-MCTD, SSc-overlap and SSc-only group. We performed univariate comparison of clinical features by ANOVA or chi-square, and survival analysis using Kaplan-Meier curves, Wilcoxon test and Cox regression. Result(s): Of 1728 patients, 102(5.9%) had SSc-MCTD and 125(7.2%) SSc-overlap. Those with MCTD-SSc were more commonly Asian (18.4% vs 9.3% in SSc-overlap and 3.6% in SSc-only, P < 0.0001). Those with SSc-MCTD or SSc-overlap were more likely to have limited SSc(81-84% vs. 73.1% for SSc-only). Both SSc-MCTD and SSc-overlap groups were more likely than SSc-only to have numerous positive autoantibodies. SSc-MCTD and SSc-overlap had similar frequency of interstitial lung disease (ILD), while those with SSc-MCTD had higher frequency of pulmonary arterial hypertension (PAH) (13.7% vs 4.8% in SSc-overlap and 11% in SSc-only, P = 0.0589). Synovitis and myositis were equally common in SSc-overlap and SSc-MCTD groups. SSc-MCTD or SSc-overlap conferred a higher likelihood of immunosuppression exposure than SSc-only. Overall survival was better in SSc-MCTD than SSc-overlap or SSc-only. However, scleroderma-specific antibodies also predicted survival, with ANA-centromere or anti-RNP conferring better survival than anti-Scl-70 or anti-RNA polymerase 3. SSc-MCTD and SSc-overlap had lower allcause mortality following diagnosis of ILD and PAH than patients with SSc-only. Conclusion(s): This study reveals significant clinical and survival differences betw

BACKGROUND Hepatic encephalopathy (HE) is a reversible neuropsychiatric complication of liver cirrhosis and occurs in up to 50% of cirrhotic patients. Studies examining the prognostic significance of HE are limited despite the high prevalence in cirrhosis. AIM To define the clinical outcomes of patients after an episode of HE treated with current standards-of-care. METHODS All patients hospitalised with HE requiring Rifaximin to 3 tertiary centres over 46-mo (2012-2016) were identified via pharmacy dispensing records. Patients with hepatocellular carcinoma and those prescribed Rifaximin prior to admission were excluded. Medical records were reviewed to determine baseline characteristics and survival. The Kaplan-Meier method was used to calculate survival probability. Univariate survival analysis was performed with variables reaching statistical significance included in a multivariate analysis. The primary outcome was 12-mo mortality following commencement of Rifaximin. RESULTS 188 patients were included. Median age was 57 years (IQR 50-65), 71% were male and median model for end stage liver disease and Child Pugh scores were 25 (IQR 18-31) and 11 (IQR 9-12) respectively. The most common causes of cirrhosis were alcohol (62%), hepatitis C (31%) and non-alcoholic fatty liver disease (20%). A precipitating cause for HE was found in 92% patients with infection (43%), GI bleeding (16%), medication non-compliance (15%) and electrolyte imbalance (14%) the most common. During a mean follow up period of 12 +/- 13 mo 107 (57%) patients died and 32 (17%) received orthotopic liver transplantation. The most common causes of death were decompensated chronic liver disease (57%) and sepsis (19%). The probability of survival was 44% and 35% at 12- A nd 24-mo respectively. At multivariate analysis a model for end stage liver disease > 15 and international normalised ratio reached statistical significance in predicting mortality. CONCLUSION Despite advances made in the management of H

Background: Historically, first generation anti-androgens (FGA) such as bicalutamide result in PSA50 response rates (>=50% reduction in PSA) of 20% in early castration resistant prostate cancer (CRPC). Following the emergence of novel antiandrogens, enzalutamide and abiraterone, their role has become unclear. This retrospective cohort study aimed to evaluate the real-world use of FGAs in the treatment of metastatic CRPC (mCRPC). Method(s): The electronic CRPC Australian Database (ePAD) was interrogated to identify patients with CRPC. Use of FGAs was determined and clinicopathological features and survival data were retrieved. Differences between patient groups were compared using T-tests and Chi-Square analyses. Survival analyses utilised the Kaplan Meier method and differences compared using log-rank tests. Result(s): We identified 634 mCRPC patients with median follow-up time 21.9 months. 322 (51%) were treated with FGAs. These patients were more likely to have lower Gleason grade group at diagnosis (p = 0.04), increased time to CRPC (median 25.6mo versus 16.0mo, p < 0.0001) and less likely to have visceral metastases (5.0% v 11.2%, p = 0.005)). 119 (37%) patients achieved a PSA50 response; these patients had a significantly greater overall survival (HR = 0.63, p = 0.0001). There were no significant differences in subsequent systemic therapy choice, PSA response rates or duration of therapy between patients who received FGAs and those who did not.However, patients who received FGAs were less likely to have had prior upfront docetaxel chemotherapy (p < 0.0001). Conclusion(s): In this ePAD study, FGAs were commonly used in lowerrisk mCRPC, and did not significantly influence choice or duration of subsequent systemic therapy. A PSA50 response to FGA therapy is an important prognostic marker in mCRPC, as demonstrated by significant improvement in overall survival. Longer follow-up is required to evaluate the long-term effects on efficacy of subsequent therapies and po

Background:NPPs (Named Patient Programs) can provide controlled access to treatment in response to unsolicited requests by physicians for specific patients before medicines become commercially available. In 2014, a global ibrutinib NPP was opened for patients with relapsed or refractory Chronic Lymphocytic Leukemia (CLL) in multiple countries, including Australia. The program closed in Australia in November 2017. Aim(s): To analyse duration on ibrutinib treatment for patients with relapsed/refractory CLL enrolled in a NPP in Australia. Method(s):A retrospective cohort analysis was conducted using baseline patient characteristics such as age, sex, received 3 or more prior lines of therapy, etc. (collected on a binary scale, e.g., age <65 years versus >=65 years) entered by treating physicians when enrolling patients into the NPP via the Janssen Managed Access portal (MacWeb). Patients were considered to be on treatment until they were reported as discontinued. Treatment duration was estimated from the date of first supply to date of last resupply. This real-world estimate of treatment duration was compared to time to treatment discontinuation in the ibrutinib arm of the RESONATE trial, as reported in Brown et al Leukemia, 32, 83-91 (2018). Time on treatment was evaluated descriptively using Kaplan- Meier (KM) curves, and statistical testing was conducted using log-rank test. Result(s): Of the 1,015 patients treated with ibrutinib in the NPP in Australia from 2014 to 2017, 68% were male, 73% were 65 years or older, and 43% of patients had received 3 or more prior lines of therapy before commencing in the NPP. While 226 patients (22%) discontinued treatment by the end of the NPP, 85% (95% CI: 0.82-0.87) remained on treatment for at least 12 months; median duration on treatment was not reached over the NPP period. Duration on treatment in NPP for this analysis ranged from 0 to 39 months. There was no difference in the time on treatment between the RESONATE trial and the

Objective We recently showed in a randomised clinical trial (RCT) that in infertile women tubal flushing during hysterosalpingography (HSG) with oil-based contrast resulted in more continuing pregnancies in comparison to the use of waterbased contrast at 6 months after randomisation (39.7% versus 29.1% (RR 1.37, 95% CI 1.16-1.61, P < 0.001)). However, it is unclear whether this difference in continuing pregnancies persists beyond 6 months of follow up. Design This is a retrospective cohort study of the H2Oil trial, a Dutch multi-center RCT in which 1119 women were included and randomised to HSG with oil-based contrast (n = 557) or waterbased contrast (n = 562). Here, we present the fertility outcomes at 3 years after randomisation. Materials and methods All 1119 participants were contacted by their treating physician and were asked to complete questionnaires about any fertility treatments and pregnancies after participating in the H2Oil study. Additionally, medical files were reviewed. Primary outcome was the first continuing pregnancy within 36 months after randomisation. We also compared naturally conceived pregnancies, pregnancies conceived after IUI and IVF and time to continuing pregnancy. Results In total, 383 continuing pregnancies were accomplished in the oil-based contrast group versus 344 continuing pregnancies in the water-based contrast group. The cumulative continuing pregnancy rate 3 years after randomisation was 83.2% (95% CI: 79.3-87.1%) in the oil-based contrast group versus 80.7% (95% CI: 76.4-85.0%) in the water-based contrast group. The Kaplan- Meier survival curves for time to continuing pregnancy were significantly different in favour of the oil-based contrast group (median time to continuing pregnancy 10.00 versus 14.83 months, P-value log-rank test 0.001). Of the 383 continuing pregnancies in the oil-based contrast group, 207 (54.3%) were naturally conceived, 114 (29.8%) after IUI and 60 (15.7%) after IVF/ICSI. Of the 344 continuing pregnanci

Background and Aim: Entecavir (ETV) and tenofovir (TDF) are potent antiviral therapies for chronic hepatitis B (CHB). Data remain limited on the long-term (> 48 weeks) efficacy and safety of ETV and TDF in patients with CHB managed in a tertiary care setting, particularly treatmentexperienced and cirrhotic patients. We evaluated the long-term safety and efficacy of ETV and TDF in a large heterogeneous cohort of initial and treatment-experienced patients with CHB. Method(s): We conducted a multicenter retrospective cohort study of patients with CHB aged >= 18 years who received either ETV or TDF for >= 6 months. Patients were treated at seven tertiary health care networks across Melbourne, Australia, between January 2007 and January 2017. The primary end-points were undetectable hepatitis B virus (HBV)-DNA suppression (viral load [VL] of < 15 IU/mL) and alanine aminotransferase (ALT) normalization (American Association for the Study of Liver Diseases criteria). The rate of HBeAg and HBsAg loss/seroconversion, adverse events (AEs), and clinical outcomes, such as hepatocellular carcinoma and hepatic decompensation, were also evaluated. Result(s): Of the 1093 patients in the cohort, 68.89% were male, and the mean age was 48.28 +/- 13.18 years. At baseline, 28.73% were cirrhotic, and 30.28% were treatment-experienced. Baseline mean HBV-DNA VL was 4.63 +/- 2.14 log10 IU/mL. A total of 779 patients (71.27%) received ETV and 314 (28.73%) received TDF, with median treatment durations of 37 (IQR, 20-56) and 24.5 (IQR, 15-31) months, respectively. In the ETV group, 34% were HBeAg seropositive, and in the TDF group, 42.52% were. The Kaplan-Meier curve estimated probability of complete HBV-DNA suppression on ETV or TDF was 42.82% at 10 months, 69.57% at 20 months, and 83.31% at 30 months. Multivariate Cox regression analysis of the entire cohort identified baseline cirrhosis (hazard ratio [HR], 0.54; 95% CI, 0.32-0.91; P = 0.02) as an independent negative predictor for HBV-DNA s

Background Stage I/II or early-stage follicular lymphoma (ESFL) is considered potentially curable with radiotherapy (XRT). While XRT does achieve local disease control in >90% of cases, more than half the patients (pts) relapse by 10 years (yr), generally outside of the radiation field. A recent randomized controlled trial (TROG 99.03) demonstrated that combined modality therapy (CMT), with sequential XRT and systemic therapy, significantly improved PFS but not overall survival (OS) compared to XRT alone in ESFL. However, only half the pts were staged with F-FDG positron emission tomography and computed tomography (PET) and 58% of CMT pts did not receive rituximab.Compared with CT staging, 20-60% of cases are upstaged by PET. Consequentially, there are limitations in applying this trial to modern populations. Despite the support of current guidelines, only one third of pts in clinical practice are treated with XRT. This suggests a need to better understand the role of other treatments, including watchful waiting (WW), in the PETera. Our aim was to compare outcomes with real-world treatment approaches in rigorously staged ESFL patients. Methods We conducted an international, multicenterretrospective study of stage I and II FL pts rigorously staged with bone marrow biopsy and PET. Eligible pts were >18yr with newly-diagnosed grade 1-3A FL and >=3 months follow up. Primary outcome measures were overall response rate (ORR), progression free survival (PFS), OS and risk of transformation. Survival curves were estimated with the Kaplan-Meier method and uni- and multivariate analysis was performed using Cox regression model. Results A total of 387 pts treated at 13 Australian and 3 Canadian centres between 2005-2017 were studied. Median follow-up was 45 months (range 3.1 - 164.0).5-yrPFS and OS rates were 73.5% (95% CI 66.0-78.5) and 94.4% (95% CI 89.4-93.6) respectively. 22 patients had stage IE duodenal FL with 5- yr PFS and OS rates of 100% and 100% respectively. Conside

Introduction: Frailty is a clinically important, treatable trait that rarely features in Australian respiratory care models for patients with acute exacerbations of chronic obstructive pulmonary disease (AECOPD). This study evaluated the prevalence of frailty in patients with AECOPD and its clinical relevance. Method(s): 74 patients with AECOPD (mean FEV1 47.5%, age 72years, BMI 27) were assessed within 48 hours of admission according to the Fried phenotype and Short Performance Physical Battery (SPPB), and a status of 'frail' or 'not frail' determined. Frailty prevalence was compared between instruments and associations between frailty and clinical outcomes explored via t tests, univariate logistic regression and Kaplan- Meier survival curves. Result(s): Frailty was detected in 48% (Fried) and 18% (SPPB) of patients. Compared to those who were not frail, frailty associated with increased age and falls history, decreased muscle force, gait speed and 6-minute walk distance (P<0.01 for all) and an approx. 3-fold increased risk of 90-day re-admission / mortality (P = 0.051). Conclusion(s): Frailty is common amongst patients with AECOPD and associates with poor clinical outcomes. This subgroup may require additional supportive care strategies after hospital discharge.

Objective: To investigate the long-term prognostic value of insulin-like growth factor-binding protein 1 in patients with acute myocardial infarction. Methods: Patients (n = 180) with admission glucose < 11 mmol/L without previously known diabetes admitted for an acute myocardial infarction in 1998–2000 were followed for mortality and cardiovascular events (first of cardiovascular mortality/acute myocardial infarction/stroke/severe heart failure) until the end of 2011 (median 11.6 years). Fasting levels of insulin-like growth factor-binding protein 1 at day 2 were related to outcome in Cox proportional hazard regression analyses. Results: Median age was 64 years, 69% were male and median insulin-like growth factor-binding protein 1 was 20 µg/L. Total mortality was 34% (n = 61) and 44% (n = 80) experienced a cardiovascular event during a median follow-up time of 11.6 years. After age adjustment, insulin-like growth factor-binding protein 1 was associated with all-cause (1.40; 1.02–1.93, p = 0.039) and cancer mortality (2.09; 1.15–3.79, p = 0.015) but not with cardiovascular death (p = 0.29) or cardiovascular events (p = 0.57). After adjustments also for previous myocardial infarction, previous heart failure and body mass index, insulin-like growth factor-binding protein 1 was still associated with all-cause mortality (1.38; 1.01–1.89, p = 0.046). Conclusion: In patients with acute myocardial infarction without previously known diabetes, high insulin-like growth factor-binding protein 1 was associated with long-term all-cause and cancer mortality but not with cardiovascular events., QC 20181023

Objectives Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are rare but have been increasing in incidence. Limited data on the long-term outcomes of patients with these tumors are available. Methods In this study, we used population-based data from the National Cancer Institute to assess long-term disease-specific survival (DSS) of patients who have undergone surgery for nonmetastatic disease. All patients with NETs of the stomach, small intestine, colon, rectum, appendix, and pancreas diagnosed between 1988 and 2009 were identified from the Surveillance, Epidemiology and End Results registry. Staging was derived from Surveillance, Epidemiology and End Results data using the European Neuroendocrine Tumor Society guidelines. Cases with incomplete staging data were excluded, along with those with stage IV disease, or those who did not undergo surgical resection. Results Kaplan-Meier analyses were constructed to determine DSS. Analyses were further stratified according to tumor site, stage at diagnosis, and tumor grade. Overall, 13,348 patients with GEP-NETs meeting the inclusion criteria were identified. Conclusions There were excellent outcomes for most GEP-NET patients, with a 20-year DSS of greater than 75% across all sites and stages. Pancreatic tumors had the worst outcomes, but DSS remains greater than 50% at 20 years.Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

In 2014, a landmark study was published demonstrating that the expression of androgen receptor splice variant (AR-V) 7 was a negative predictive biomarker for response to abiraterone acetate and enzalutamide in metastatic castration-resistant prostate cancer (mCRPC) patients. However, these results were not supported by the recently reported ARMOR3-SV phase III clinical trial, which employed an identical circulating tumour cell assay to assess AR-V7 expression. Therefore, the predictive utility of AR-V7 expression in mCRPC remains uncertain, as does any potential association between other AR-Vs and treatment response. To further investigate, we designed a highly sensitive and specific whole blood assay for detecting AR-V7 and AR-V9. We then examined for a correlation between baseline AR-V7/V9 status and treatment outcome in 37 mCRPC patients commencing abiraterone or enzalutamide. Of the patients, 24% (9/37) were AR-V-positive. Notably, prostate-specific antigen (PSA) response rates did not significantly differ between AR-V-positive (6/9) and AR-V-negative (18/28) patients (66% vs 64%, p = 0.9). Likewise, median PSA progression-free survival was not significantly different between AR-V-positive and AR-V-negative patients (9.2 mo vs not reached; p = 0.9). These data, which support the findings of the pivotal ARMOR3-SV clinical trial, suggest that baseline AR-V expression does not predict outcomes in mCRPC patients receiving abiraterone or enzalutamide. Patient Summary: Detection of androgen receptor splice variants (AR-Vs) in circulating tumour cells of advanced prostate cancer patients has been linked to resistance to abiraterone and enzalutamide. We designed a blood test to detect AR-Vs that can be performed more routinely than tests involving circulating tumour cells and found that patients with AR-Vs still benefit from these effective treatments. We designed a whole blood assay for the detection of androgen receptor splice variant (AR-V) 7 and AR-V9. The presence

Introduction: Cancer after kidney transplantation (KT) is a significant cause of morbidity and mortality. Choice of immunosuppressive regimenmay modify the risk of cancer. Mammalian target of rapamycin inhibitors have been shown to have anti-oncogenic effects in both animal and human studies. A large individual patient data (IPD) meta-analysis showed that sirolimus was associated with a significant reduction in the risk of cancer, but at the cost of an increased risk of death. We aimed to determine the cumulative incidence of cancer in KTrecipients randomised to de novo or early switch to everolimus (EVL)maintenance immunosuppression versus controls on standard calcineurin inhibitor (CNI) based triple therapy. Material(s) and Method(s): We included all de novo or early EVL switch randomised controlled trials (RCTs) conducted in Australia and New Zealand KT recipients between 2001 - 2012 in the IPD meta-analysis (Fig 1). Participants were linked to the Australian and New Zealand Dialysis and Transplantation Registry (ANZDATA) to capture outcomes of incident cancer and all-cause mortality. We compared treatment allocation to EVL or control, with time to first cancer occurrence using Kaplan-Meier estimates. An adjusted Cox proportional hazards model with random effects using pooled individual patient data from all trials was used to determine the overall risks of cancer and death. Results and Discussion: The 279 Australian and New Zealand participants (EVL = 192, control = 87) were followed for a median of 9.0 yrs (IQR 6.8, 9.6). Four RCTs examined EVL immunosuppression using de Novo (n=141) or early (<4 mths) (n=138) strategies in addition to either reduced dose CNI or CNI-withdrawal. The control arm consisted of cyclosporine or tacrolimus with mycophenolic acid or azathioprine and steroid maintenance therapy. The cumulative incidence of any cancer was not significantly different between EVL and control (log-rank test p = 0.8) (Fig 2). 30 (15.6%) EVL patients develope

Study question: What is the impact of the use of oil-or water-based contrast medium at hysterosalpingography (HSG) on fertility outcomes 3 years after randomization? Summary answer: Women who had their tubes flushed with oil-based con-trast had 3-year cumulative ongoing pregnancy rates of 83.2% versus 80.7% after the use of water-based contrast. What is known already: For decades it has been suggested that tubal flushing with oil-based contrast (Lipiodol) at HSG improved pregnancy, rates (Mohiyiddeen L, et al. 2015). We recently showed in a landmark trial published in the New England Journal of Medicine that in infertile women tubal flushing during HSG with oil-based contrast resulted in more ongoing pregnancies than HSG with the use of water-based contrast at 6 months after randomization(39.7% versus 29.1% (RR 1.37, 95%CI 1.16-1.61, p < 0.001)) (Dreyer et al. 2017). It is unclear whether this difference continues beyond 6 months. Study design, size, duration: This was a follow-up study of the H2Oil trial, a multi-center randomized controlled trial in the Netherlands in which 1,119 women were included and randomized to hysterosalpingography with oil-based contrast (n = 557) or water-based contrast (n = 562). Here, we present the fertility outcomes at three years after randomization. Participants/materials, setting, methods: All 1,119 participants were contacted 3-5 years after randomization, and were asked to fill in questionnaires about the fertility treatments and pregnancies. Additionally, we reviewed the medical files to record all pregnancies and fertility treatments. Primary outcome was the first ongoing pregnancy within 36 months after randomization. We also compared naturally conceived pregnancies, pregnancies conceived after IUI and IVF and time to ongoing pregnancy. Main results and the role of chance: In total, 383 ongoing pregnancies were accomplished in the oil-based contrast group versus 344 ongoing pregnancies in the water-based contrast group. The cu

Study question: Does tubal flushing with oil-versus water-based contrast at hysterosalpingography (HSG) increase the chance of a second child? Summary answer: There is no clear effect of a single procedure of tubal flushing with oil-versus water-based contrast on the chance of a second child. What is known already: For decades it has been suggested that tubal flushing with oil-based contrast(Lipiodol) at HSG improved pregnancy rates (Mohiyiddeen et al. 2015). We recently showed in a landmark trial published in the New England Journal of Medicine that in infertile women undergoing HSG tubal flushing with oil-based contrast resulted in more ongoing pregnancies than with the use of water-based contrast at 6 months after randomisation(39.7% versus 29.1% (RR 1.37, 95%CI 1.16-1.61))(Dreyer et al. 2017). While the effect of oil-flushing on conception of the first child is established, it is unclear whether tubal flushing with oil-based contrast increases the chances of subsequent children. Study design, size, duration: This was a follow-up study of the H2Oil trial, a multi-center randomized controlled trial in the Netherlands in which 1,119 women were randomized to HSG with oil-based contrast (n = 557) or water-based contrast (n = 562). Participating women were approached 3-5 years after randomization with a questionnaire about their fertility. Additionally, we reviewed the medical files to record all pregnancies and fertility treatments. Here, we present the fertility outcome in terms of a second ongoing pregnancy. Participants/materials, setting, methods: The outcome of this follow-up study was a second ongoing pregnancy (after the birth of a first child). We also assessed mode of conception and time to pregnancy. Main results and the role of chance: There were 1,119 women randomized to oil-based contrast(n = 557) or water-based contrast(n = 562). Cumulative ongoing pregnancy rates were 83.2% versus 80.7% after oil and water flushing, respectively. In the oil-based contr

Introduction: Treatment decisions for patients with hepatocellular carci-noma (HCC) are largely guided by the Barcelona Clinic Liver Cancer (BCLC) staging system; patients with BCLC-B stage HCC are typically treated with transarterial chemoembolization (TACE), and those with BCLC-C with sorafenib. There is, however, a select subgroup of patients in BCLC-B or-C stages who are treated with selective internal radiation therapy (SIRT). SIRT has theoretical advantages over TACE, but as its use in HCC is not funded, there are limited data guiding which patients are the best candidates. Anecdotally, there is a subgroup of SIRT patients who have excellent outcomes. Our aims were to catalogue the clinical features and outcomes of patients with HCC who have received SIRT over the past 10 years at six institutions and to use a propensity matched comparator group of patients who have received drug-eluting bead (DEB)-TACE to identify those better suited to SIRT. Method(s): Participants were identified by a search of each site's hepatoma database. Inclusion criteria were (i) age >18 years, (ii) diagnosis of HCC made as per EASL-EORTIC and AASLD guidelines, (iii) received at least one session of either DEB-TACE or SIRT, and (iv) have had at least 6 months' follow-up after the treatment session. The endpoints used were overall survival from the time of treatment, time to progression, and radiological response. Complications were documented from patient files. Base-line characteristics were assessed using Cox regression. Statistical and P values were assessed using ANOVA univariate and multivariate analysis. Survival curves and response curves were made using the Kaplan-Meier method. Achieved power was also assessed to aid future prospective studies. Result(s): Interim results of the first 10 (of more than 50) SIRT patients show that all patients were male, with a median age at time of treatment of 66.3 years (range, 54.7-86.5). SIRT patients had a mean tumor size of 65.8 +/- 39.6 m

Background/Purpose: The clinical associations of anti-Th/To antibodies (Abs) are not fully established, and until recently immunoprecipitation (IP) was the only reliable assay. Using IP, anti-Th/To Abs are mostly detected in SSc but other reported associations include ILD. Our objective was to examine clinical correlates of anti-Th/To Abs targeted against three different proteins associated with the Th/To autoantigen complex in SSc. We used a commercially available hPOP1 immunoblot and a recently described Rpp25 and Rpp38 chemiluminescence assay in a multinational cohort of SSc. Method(s): Cross sectional retrospective study including 1312 patients from the Australian Scleroderma Cohort study (ASCS), Canadian Scleroderma Research Group (CSRG) and the Genetics versus Environment in Scleroderma Outcome Study (GENISOS). Demographic and clinical variables were harmonized and sera tested for anti-Th/To Abs using hPOP1 (EUROLINE, Eurimmun, Lubeck, Germany) and Rpp25/38 (QUANTA Flash Assay, Inova Diagnostics Inc, San Diego, CA). Rpp25/38 was defined as positive if either one or both autoantibodies were present. ILD was determined by high resolution CT chest (HRCT) or a published algorithm [1] which allows diagnosis of ILD by chest X-ray showing increased interstitial markings or fibrosis and/or physician reported "velcro-like crackles" when HRCT is not available. Descriptive statistics summarise baseline demographic and clinical variables and Kaplan Meier analyses were used to assess survival Results: Patients had median (interquartile range) age at disease onset 46.3y (18.6) and disease duration 5.1y (11.4) at recruitment. hPOP1 was positive in 2.4% and Rpp25/38 was positive in 4.5% patients. Notably hPOP1 and Rpp25/38 identified overlapping patient populations (p<0.001). Median age of disease onset for hPOP1 patients was 48.9y (23.3) and for Rpp25/38 patients was 48.8y (17.3). hPOP1 was associated with ILD on HRCT chest (OR:5.16; p=0.02) but not ILD by algorithm (OR:1.19

Background:No therapies are approved for MDS after HMA failure. 04-24 was a single-arm study to evaluate best BMBL response as a potential surrogate for OS in higher-risk (HR) MDS pts who progressed on or after an HMA. Rigo is a Ras-mimetic that inhibits the RAS-RAF-MEK pathway, which is frequently activated in HR MDS (Athuluri-Divakar Cell 2016; Gil-Bazo Cancer Biol Ther 2016). Method(s):Eligible MDS pts had 5-30% BMBL confirmed within 6 wks pre-study and progression per International Working Group (IWG) 2006 criteria on or after HMAs within 2 yrs. Rigo 1800 mg/24 hrs was continuously infused over 72 hrs q 2 wks x 8 cycles, then q 4 wks until progression or unacceptable toxicity. Primary endpoint was relationship of best BMBL IWG response to OS by Kaplan Meier method. Result(s):64 pts were treated (median 5 cycles, range 1-32+), with 61% male, median age 73 (range 47-87), median prior HMA duration 10.8 mos (range 1.2-70.2). Revised International Prognostic Scoring System scores were low 2%, intermediate 11%, high 27%, very high 53%, and unknown 8%. >=Grade 3 adverse events in >=10% of pts were anemia 19%, thrombocytopenia 19%, and febrile neutropenia 16%. At the analysis time 40 pts (63%) had died. Best BMBL IWG response was marrow complete response (mCR) 14 pts (22%), stable disease (SD) 30 (47%), progressive disease (PD) 15 (23%), and failure (early death/withdrawal) 5 (8%); 2 mCR pts had transplant. Median OS was 7.0 mos (95% confidence interval 4.8-10.8). Landmark median OS (from day of best BMBL response) was mCR not reached; SD 6.3 mos; PD 3.3 mos. Median OS of mCR+SD was 8.5 mos, with log-rank p = 0.011 (mCR+SD OS to PD OS). Conclusion(s):BMBL response is a predictor of survival for MDS pts receiving Rigo after HMA failure, confirming findings in earlier Phase 1/2 studies (Silverman ASCO 2015 Abstr 7017). Based on earlier results identifying an MDS subset benefitting from Rigo (Garcia-Manero Lancet Oncol 2016; ASCO 2016 Abstr 165681), a randomized Phase 3 tr

Purpose: This study aimed to evaluate the long-term survival of all patients who participated in a pilot randomised trial of an early nutritional intervention for adults with upper gastrointestinal cancer. It also sought to identify factors that predicted patient mortality. Method(s): All participants (n = 21) who were randomised into the original study were followed for a maximum of 5 years and 2 months (final follow-up April 2016). The primary outcome measure was time from date of recruitment until date of death, ascertained by the Victorian Cancer Registry and/or Monash Health Scanned Medical Records. Secondary analyses were conducted to identify factors that adversely affected survival. Result(s): At the end of the follow-up period, three patients were alive in the nutrition intervention group whilst only two patients were living from the standard care group. Visual evaluation of the Kaplan-Meier survival curves demonstrated a possible survival benefit from being exposed to the intervention between 6 months and 1.4 years post-recruitment, though this benefit dissipated soon after. The intervention was not associated with increased survival in univariate analyses, but was after adjustment for other factors found to adversely impact on survival (adjusted hazard ratio 0.12 (95% CI 0.02-0.72) p = 0.02). These factors were being a smoker (14.2 (1.43 to 140.67), p = 0.02); low baseline physical functioning (1.11 (1.01 to 1.21), p = 0.03); high baseline fatigue (1.09 (1.02-1.16), p = 0.007); and high baseline dyspnoea (1.08 (1.02-1.13), p = 0.003). Conclusion(s): Early and intensive nutrition intervention may increase the survival of people with upper gastrointestinal cancer.Copyright © 2017, Springer-Verlag GmbH Germany.