Factors associated with favourable pathological tumour response after neoadjuvant chemotherapy in patients with pancreatic ductal adenocarcinoma.

INTRODUCTION: Pathological response of pancreatic ductal adenocarcinoma (PDAC) to neoadjuvant chemotherapy (NAT) has been associated with oncological outcome. The aim of the study was to investigate factors associated with favourable tumour regression in patients undergoing pancreatic resection for PDAC. METHODS: Patients who received NAT before undergoing PDAC resection at two institutions were reviewed. Tumour regression grading (TRG) was scored according to the College of American Pathologists (CAP) system. Interactions between chemotherapy, tumour and surgical factors with TRG were explored. RESULTS: 54 patients were identified, with 12 (22%) displaying a favourable response to NAT. The type of chemotherapy agent received, the number of cycles or a dose reduction during NAT course was not significantly different between the groups. The time from diagnosis to chemotherapy and time from end of chemotherapy to surgery were also similar between the groups. A favourable TRG was associated with greater disease-free survival median 33.2 months vs. 10.3 months; p = 0.0) but not overall survival (median 43.8 months vs. 32.3 months; p = 0.200), which may be due to small sample size. CONCLUSIONS: Chemotherapy factors were not significantly related to a favourable response to NAT. Future studies should seek to identify modifiable factors associated with a favourable TRG.

Progress and potential of brain organoids in epilepsy research.

Epilepsies are disorders of the brain characterised by an imbalance in electrical activity, linked to a disruption in the excitation and inhibition of neurons. Progress in the epilepsy research field has been hindered by the lack of an appropriate model, with traditionally used 2D primary cell culture assays and animal models having a number of limitations which inhibit their ability to recapitulate the developing brain and the mechanisms behind epileptogenesis. As a result, the mechanisms behind the pathogenesis of epilepsy are largely unknown. Brain organoids are 3D aggregates of neural tissue formed in vitro and have been shown to recapitulate the gene expression patterns of the brain during development, and can successfully model a range of epilepsies and drug responses. They thus present themselves as a novel tool to advance studies into epileptogenesis. In this review, we discuss the formation of brain organoids, their recent application in studying genetic epilepsies, hyperexcitability dynamics and oxygen glucose deprivation as a hyperexcitability agent, their use as an epilepsy drug testing and development platform, as well as the limitations of their use in epilepsy research and how these can be mitigated.

The Role of Sleep in Links Between Daily Interpersonal Stress and Internalizing and Externalizing Symptoms During Middle Childhood.

Background: Interpersonal stress has been consistently linked with poorer adjustment, and healthy sleep may play a promotive or protective role in this relation. However, little is known regarding such associations among children. The current study examined longitudinal associations between daily interpersonal stress, sleep, and internalizing/externalizing symptoms during middle childhood. Methods: At age 8 years, participants wore actigraphy watches for 7 days to capture sleep, and primary caregivers reported on children's daily interpersonal stress, internalizing/externalizing symptoms, and sleep problems. At age 9 years, children self-reported symptoms. Results: Greater daily interpersonal stress at age 8 years predicted greater internalizing/externalizing symptoms at age 9 years. Higher sleep efficiency predicted fewer externalizing symptoms. Sleep duration moderated links between interpersonal stress and internalizing/externalizing symptoms, but associations were positive and significant for children with average and high duration only. Conclusion: Findings advance our understanding of links between interpersonal stress, sleep, and child adjustment and can inform targeted family and school interventions.

Using co-design to identify intervention components to address unhealthy dietary and activity behaviours in New Zealand South Asians.

There is an urgent need to develop sustainable and impactful interventions to mitigate the high risk of diet-related non-communicable diseases (diet-NCDs) in South Asians living in high-income countries. The current study using a co-design methodology aimed to identify community-led intervention components (solutions) to address barriers and enablers of disease-promoting dietary and physical activity behaviours in New Zealand South Asians. Data were collected from South Asian immigrants aged 25-59 years via three focus group discussions (n = 21) and 10 telephone or face-to-face interviews between 2018 and 2019. The thematic analysis resulted in identifying 22 barrier and enabler codes and 12 solution codes which were summarised under five themes. The key solutions (intervention components) to mitigate the identified target behaviours were providing recipes for using local vegetables in South Asian cuisine, information on the nutritional quality of frozen vegetables and canned lentils, simple home gardening techniques, the saturated fat content of dairy foods, interpreting nutrition labels, optimal portion sizes of foods, and framing low-fat messages positively. Similarly, group-based activities with peer support such as walking, cultural dancing and community sports like cricket, football, and tennis were the identified solutions to increase physical activity levels. The identified solutions for health promoting dietary habits and physical activity levels could be part of any targeted multicomponent health promoting programme to reduce the risk of diet-NCDs in South Asian immigrants.

SIMAP500: A novel risk score to identify recipients at higher risk of hepatocellular carcinoma recurrence following liver transplantation.

BACKGROUND: Recurrence of hepatocellular carcinoma (HCC) following liver transplantation (LT) has a devastating influence on recipients' survival; however, the risk of recurrence is not routinely stratified. Risk stratification is vital with a long LT waiting time, as that could influence the recurrence despite strict listing criteria. AIM: This study aims to identify predictors of recurrence and develop a novel risk prediction score to forecast HCC recurrence following LT. METHODS: A retrospective review of LT for HCC recipients at University Hospitals Birmingham between July 2011 and February 2020. Univariate and multivariate analyses were performed to identify recurrence predictors, based on which the novel SIMAP500 (satellite nodules, increase in size, microvascular invasion, AFP > 500, poor differentiation) risk score was proposed. RESULTS: 234 LTs for HCC were performed with a median follow-up of 5.3 years. Recurrence developed in 25 patients (10.7%). On univariate analyses, RETREAT score > 3, α-fetoprotein (AFP) at listing 100-500 and > 500, bridging, increased tumour size between imaging at the listing time and explant histology, increase in the size of viable tumour between listing and explant, presence of satellite nodules, micro- and macrovascular invasion on explant and poor differentiation of tumours were significantly associated with recurrence, based on which, the SIMAP500 risk score is proposed. The SIMAP500 demonstrated an excellent predictive ability (c-index = 0.803) and outperformed the RETREAT score (c-index = 0.73). SIMAP500 is indicative of the time to disease recurrence. CONCLUSION: SIMAP500 risk score identifies the LT recipients at risk of HCC recurrence. Risk stratification allows patient-centric post-transplant surveillance programs. Further validation of the score is recommended.

Parent and healthcare professional experiences of critical congenital heart disease in New Zealand to advance health equity.

BACKGROUND: Higher odds of survival have been reported in European infants compared to Indigenous Maori and Pasifika infants with critical congenital heart disease in New Zealand. We therefore aimed to understand how to mitigate this disparity by investigating the parent and healthcare professional experiences' of critical congenital heart disease healthcare in New Zealand. METHODS: A prospective qualitative study utilising semi-structured interviews was conducted on a cohort of purposefully sampled parents and health professionals with experience of critical congenital heart disease healthcare in New Zealand. Parents were recruited after a fetal critical congenital heart disease diagnosis and offered two interviews at least three months apart, whilst multidisciplinary fetal and cardiosurgical health professionals were interviewed once. Interviews were recorded and transcribed verbatim before coding, categorization and qualitative analysis. RESULTS: During 2022 and 2023, 45 people participated in 57 interviews (25 parents: 19 mothers, 6 fathers; Indigenous Maori, n = 5; Pasifika, n = 6; Asian, n = 4; European, n = 10; and 20 healthcare professionals: European n = 17). The three lessons learned from participants were: (1) Minoritized groups experience disparate healthcare quality; (2) healthcare systems are under-resourced to provide equitable support for the differential needs of grieving parents; and (3) healthcare systems could engage minoritized families more optimally in shared decision-making. CONCLUSIONS: According to the experiences of parents and healthcare professionals, persisting inequities in CCHD healthcare quality occur by ethnic group, with the New Zealand healthcare system privileging European families. The concepts from this study could be translated by healthcare leaders, policymakers, and professionals into evidence-based healthcare system improvements to enhance experiences for non-European families more broadly.

MTGR1 is required to maintain small intestinal stem cell populations.

Undifferentiated intestinal stem cells (ISCs) are crucial for maintaining homeostasis and resolving injury. Lgr5+ cells in the crypt base constantly divide, pushing daughter cells upward along the crypt axis where they differentiate into specialized cell types. Coordinated execution of complex transcriptional programs is necessary to allow for the maintenance of undifferentiated stem cells while permitting differentiation of the wide array of intestinal cells necessary for homeostasis. Previously, members of the myeloid translocation gene (MTG) family have been identified as transcriptional co-repressors that regulate stem cell maintenance and differentiation programs in multiple organ systems, including the intestine. One MTG family member, myeloid translocation gene related 1 (MTGR1), has been recognized as a crucial regulator of secretory cell differentiation and response to injury. However, whether MTGR1 contributes to the function of ISCs has not yet been examined. Here, using Mtgr1-/- mice, we have assessed the effects of MTGR1 loss specifically in ISC biology. Interestingly, loss of MTGR1 increased the total number of cells expressing Lgr5, the canonical marker of cycling ISCs, suggesting higher overall stem cell numbers. However, expanded transcriptomic and functional analyses revealed deficiencies in Mtgr1-null ISCs, including deregulated ISC-associated transcriptional programs. Ex vivo, intestinal organoids established from Mtgr1-null mice were unable to survive and expand due to aberrant differentiation and loss of stem and proliferative cells. Together, these results indicate that the role of MTGR1 in intestinal differentiation is likely stem cell intrinsic and identify a novel role for MTGR1 in maintaining ISC function.

Pembrolizumab-induced Myasthenia Gravis and Myocarditis.

As the use of immune checkpoint inhibitors (ICPi) such as pembrolizumab is rapidly expanding in the field of immuno-oncology, it is crucial for healthcare providers to be aware of their immune-related adverse events (irAE) which are thought to be driven by augmented immune response of T-cells. While neurologic irAE are underrepresented in literature, their consequences could lead to fatal outcomes. In this report, we describe the case of a patient with excellent performance status prior to pembrolizumab therapy who subsequently suffered myasthenic crisis eventually requiring tracheostomy and long-term mechanical ventilation.

TIGIT+Tfh show poor B-helper function and negatively correlate with SARS-CoV-2 antibody titre.

Circulating follicular helper T cells (cTfh) can show phenotypic alterations in disease settings, including in the context of tissue-damaging autoimmune or anti-viral responses. Using severe COVID-19 as a paradigm of immune dysregulation, we have explored how cTfh phenotype relates to the titre and quality of antibody responses. Severe disease was associated with higher titres of neutralising S1 IgG and evidence of increased T cell activation. ICOS, CD38 and HLA-DR expressing cTfh correlated with serum S1 IgG titres and neutralising strength, and interestingly expression of TIGIT by cTfh showed a negative correlation. TIGIT+cTfh expressed increased IFNγ and decreased IL-17 compared to their TIGIT-cTfh counterparts, and showed reduced capacity to help B cells in vitro. Additionally, TIGIT+cTfh expressed lower levels of CD40L than TIGIT-cTfh, providing a potential explanation for their poor B-helper function. These data identify phenotypic changes in polyclonal cTfh that correlate with specific antibody responses and reveal TIGIT as a marker of cTfh with altered function.

Pseudomonas fluorescens 15 small RNA Pfs1 mediates transgenerational epigenetic inheritance of pathogen avoidance in C. elegans through the Ephrin receptor VAB-1.

C. elegans are exposed to a variety of pathogenic and non-pathogenic bacteria species in their natural environment. Correspondingly, C. elegans has evolved an ability to discern between nutritive and infectious bacterial food sources. Here we show that C. elegans can learn to avoid the pathogenic bacteria Pseudomonas fluorescens 15 (PF15), and that this learned avoidance behavior is passed on to progeny for four generations, as we previously demonstrated for Pseudomonas aeruginosa (PA14) and Pseudomonas vranovensis, using similar mechanisms, including the involvement of both the TGF-ß ligand DAF-7 and Cer1 retrotransposon-encoded virus-like particles. PF15 small RNAs are both necessary and sufficient to induce this transgenerational avoidance behavior. Unlike PA14 or P. vranovensis, PF15 does not use P11, Pv1, or a small RNA with maco-1 homology for this avoidance; instead, an unrelated PF15 small RNA, Pfs1, that targets the C. elegans vab-1 Ephrin receptor gene is necessary and sufficient for learned avoidance, suggesting the evolution of yet another bacterial sRNA/C. elegans gene target pair involved in transgenerational inheritance of pathogen avoidance. As VAB-2 Ephrin receptor ligand and MACO-1 knockdown also induce PF15 avoidance, we have begun to understand the genetic pathway involved in small RNA targeted pathogenic avoidance. Moreover, these data show that axon guidance pathway genes (VAB-1 and VAB-2) have previously unknown adult roles in regulating neuronal function. C. elegans may have evolved multiple bacterial specificity-encoded small RNA-dependent mechanisms to avoid different pathogenic bacteria species, thereby providing progeny with a survival advantage in a dynamic environment.

Patient Engagement with Conversational Agents in Health Applications 2016-2022: A Systematic Review and Meta-Analysis.

Clinicians and patients seeking electronic health applications face challenges in selecting effective solutions due to a high market failure rate. Conversational agent applications ("chatbots") show promise in increasing healthcare user engagement by creating bonds between the applications and users. It is unclear if chatbots improve patient adherence or if past trends to include chatbots in electronic health applications were due to technology hype dynamics and competitive pressure to innovate. We conducted a systematic literature review using Preferred Reporting Items for Systematic reviews and Meta-Analyses methodology on health chatbot randomized control trials. The goal of this review was to identify if user engagement indicators are published in eHealth chatbot studies. A meta-analysis examined patient clinical trial retention of chatbot apps. The results showed no chatbot arm patient retention effect. The small number of studies suggests a need for ongoing eHealth chatbot research, especially given the claims regarding their effectiveness made outside the scientific literatures.

Production benefits on encoding are modulated by language experience: Less experience may help.

Several lines of research have shown that performing movements while learning new information aids later retention of that information, compared to learning by perception alone. For instance, articulated words are more accurately remembered than words that are silently read (the production effect). A candidate mechanism for this movement-enhanced encoding, sensorimotor prediction, assumes that acquired sensorimotor associations enable movements to prime associated percepts and hence improve encoding. Yet it is still unknown how the extent of prior sensorimotor experience influences the benefits of movement on encoding. The current study addressed this question by examining whether the production effect is modified by prior language experience. Does the production effect reduce or persist in a second language (L2) compared to a first language (L1)? Two groups of unbalanced bilinguals, German (L1) - English (L2) bilinguals (Experiment 1) and English (L1) - German (L2) bilinguals (Experiment 2), learned lists of German and English words by reading the words silently or reading the words aloud, and they subsequently performed recognition tests. Both groups showed a pronounced production effect (higher recognition accuracy for spoken compared to silently read words) in the first and second languages. Surprisingly, the production effect was greater in the second languages compared to the first languages, across both bilingual groups. We discuss interpretations based on increased phonological encoding, increased effort or attention, or both, when reading aloud in a second language.

Evaluating whether Prostate Cancer UK's risk checker is a help or hindrance to prostate-specific antigen testing policy: a mixed-methods study.

BACKGROUND: The UK has an informed choice testing policy for prostate cancer. The prostate-specific antigen (PSA) blood test is available for free to any man aged ≥50 years who requests it and has been informed of the harms and benefits. This policy leads to differences in PSA testing rates, which can exacerbate health inequalities. AIM: To assess whether Prostate Cancer UK's risk checker helps men at risk of prostate cancer make an informed choice about the PSA test. DESIGN & SETTING: Mixed-methods study in the UK. METHOD: In total, 1181 men at risk, their partners, and clinical experts participated in surveys, focus groups, and one-to-one interviews. Data on risk checker completions by sociodemographic factors were analysed over time. Data from general practices that sent the risk checker to their patients were collected and analysed for service monitoring purposes. RESULTS: There was a strong assumption that testing must be good, and therefore a need to emphasise the pros and cons of the test and that having it was the patient's decision. Men believed their GP would invite them for PSA testing. On the impact of the risk checker, 79.6% of men who completed it had at least one prostate cancer risk factor; the average time they interacted with the information in the tool was 9 minutes 28 seconds; and 75.7% felt the tool had equipped them to make an informed choice. CONCLUSION: Online decision-making tools, such as the risk checker, can help reach men at high risk of prostate cancer and support them in making an informed choice about the PSA test.

Interplay in galectin expression predicts patient outcomes in a spatially restricted manner in PDAC.

BACKGROUND: Galectins (Gal's) are a family of carbohydrate-binding proteins that are known to support the tumour microenvironment through their immunosuppressive activity and ability to promote metastasis. As such they are attractive therapeutic targets, but little is known about the cellular expression pattern of galectins within the tumour and its neighbouring stromal microenvironment. Here we investigated the cellular expression pattern of Gals within pancreatic ductal adenocarcinoma (PDAC). METHODS: Galectin gene and protein expression were analysed by scRNAseq (n=4) and immunofluorescence imaging (n=19) in fibroblasts and epithelial cells of pancreatic biopsies from PDAC patients. Galectin surface expression was also assessed on tumour adjacent normal fibroblasts and cancer associated primary fibroblasts from PDAC biopsies using flow cytometry. RESULTS: scRNAseq revealed higher Gal-1 expression in fibroblasts and higher Gal-3 and -4 expression in epithelial cells. Both podoplanin (PDPN+, stromal/fibroblast) cells and EpCAM+ epithelial cells expressed Gal-1 protein, with highest expression seen in the stromal compartment. By contrast, significantly more Gal-3 and -4 protein was expressed in ductal cells expressing either EpCAM or PDPN, when compared to the stroma. Ductal Gal-4 cellular expression negatively correlated with ductal Gal-1, but not Gal-3 expression. Higher ductal cellular expression of Gal-1 correlated with smaller tumour size and better patient survival. CONCLUSIONS: In summary, the intricate interplay and cell-specific expression patterns of galectins within the PDAC tissue, particularly the inverse correlation between Gal-1 and Gal-4 in ducts and its significant association with patient survival, highlights the complex molecular landscape underlying PDAC and provides valuable insights for future therapeutic interventions.

Histopathological findings from the investigation of paediatric acute hepatitis of unknown aetiology, United Kingdom 2022.

In 2022, there were global reports of increased numbers of acute hepatitis not explained by hepatitis A-E virus infection in children. This manuscript summarises histopathology results from 20 patients in the United Kingdom who underwent liver transplant or had a liver biopsy as part of aetiological investigations. All available histopathological samples were reviewed centrally as part of the outbreak investigation. A working group comprised of infection specialists, hepatologists and histopathologists met virtually to review the cases, presentation, investigations and histopathology. All 20 liver samples had evidence of inflammation without significant interface activity, and submassive confluent pan-lobular or multilobular hepatocellular necrosis. Overall, the predominant histopathological findings were of acute nonspecific hepatitis with submassive hepatic necrosis and central vein perivenulitis and endothelitis. Histopathological findings were a poor indicator of aetiology.

Risk of low energy availability and nutrition knowledge among female team sport athletes.

BACKGROUND: Nutrition knowledge influences adequate dietary intake in athletes. Inadequate dietary intakes can result in low energy availability (LEA) which can lead to relative energy deficiency in sport (RED-S). To date, there is little information on the relationship between nutrition knowledge and the risk of LEA in female team sport athletes. This study investigates if general and sports nutrition knowledge are associated with the risk of LEA in female team athletes. METHODS: A cross-sectional design was used. Female athletes (>16 years) who participate in team sports in New Zealand were asked to complete an online questionnaire. The LEA in Females Questionnaire and the Abridged Sport Nutrition Knowledge Questionnaire were included. LEA risk and general/sports nutrition knowledge were assessed. The relationship between LEA risk and knowledge was analyzed using the Kruskal-Wallis Test of independent variables and χ2 tests. RESULTS: Among 100 female athletes, 53% were at-risk for LEA, and 70% (N.=67) had poor nutrition knowledge. Athletes who were "at-risk" for LEA and those who were "not at-risk" for LEA did not differ statistically in terms of age (P=0.350) or BMI (P=0.576). Of those "not at risk" 54% had an A-NSK score between 50 and 60% (i.e., average knowledge), whereas 54% of the athletes who were "at risk" for LEA had poor nutrition knowledge. There was no statistical difference between the groups (P=0.273). CONCLUSIONS: The poor nutrition knowledge and the high rates of those "at risk" of LEA among team sports athletes indicates the need for more nutrition education in this population.

Adapting an equity-focused implementation process framework with a focus on ethnic health inequities in the Aotearoa New Zealand context.

BACKGROUND: Health intervention implementation in Aotearoa New Zealand (NZ), as in many countries globally, usually varies by ethnicity. Maori (the Indigenous peoples of Aotearoa) and Pacific peoples are less likely to receive interventions than other ethnic groups, despite experiencing persistent health inequities. This study aimed to develop an equity-focused implementation framework, appropriate for the Aotearoa NZ context, to support the planning and delivery of equitable implementation pathways for health interventions, with the intention of achieving equitable outcomes for Maori, as well as people originating from the Pacific Islands. METHODS: A scoping review of the literature to identify existing equity-focused implementation theories, models and frameworks was undertaken. One of these, the Equity-based framework for Implementation Research (EquIR), was selected for adaptation. The adaptation process was undertaken in collaboration with the project's Maori and consumer advisory groups and informed by the expertise of local health equity researchers and stakeholders, as well as the international implementation science literature. RESULTS: The adapted framework's foundation is the principles of Te Tiriti o Waitangi (the written agreement between Maori rangatira (chiefs) and the British Crown), and its focus is whanau (extended family)-centred implementation that meets the health and wellbeing aspirations, priorities and needs of whanau. The implementation pathway comprises four main steps: implementation planning, pathway design, monitoring, and outcomes and evaluation, all with an equity focus. The pathway is underpinned by the core constructs of equitable implementation in Aotearoa NZ: collaborative design, anti-racism, Maori and priority population expertise, cultural safety and values-based. Additionally, the contextual factors impacting implementation, i.e. the social, economic, commercial and political determinants of health, are included. CONCLUSIONS: The framework presented in this study is the first equity-focused process-type implementation framework to be adapted for the Aotearoa NZ context. This framework is intended to support and facilitate equity-focused implementation research and health intervention implementation by mainstream health services.

Real-world efficacy of single-agent belantamab mafodotin in relapsed systemic AL amyloidosis.

Systemic light chain (AL) amyloidosis is a relapsing plasma cell disorder. Therapy is limited, particularly for triple-class refractory disease. We report the use of belantamab mafodotin, a BCMA-directed drug-antibody conjugate, for relapsed AL amyloidosis, including patients traditionally excluded from clinical trials. Thirty-one patients were reviewed, with a median of three prior lines of therapy. The median follow-up was 12 months (95% CI 4-19), and a median of five doses were delivered. The best haematological overall response rate was 71%, and the complete/very good partial response was 58%. Sixty-eight percent had keratopathy and improved in all. Belantamab mafodotin has high efficacy and good tolerability in patients with relapsed AL amyloidosis.

Developing and Validating a Multivariable Prognostic-Predictive Classifier for Treatment Escalation of Oropharyngeal Squamous Cell Carcinoma: The PREDICTR-OPC Study.

PURPOSE: While there are several prognostic classifiers, to date, there are no validated predictive models that inform treatment selection for oropharyngeal squamous cell carcinoma (OPSCC).Our aim was to develop clinical and/or biomarker predictive models for patient outcome and treatment escalation for OPSCC. EXPERIMENTAL DESIGN: We retrospectively collated clinical data and samples from a consecutive cohort of OPSCC cases treated with curative intent at ten secondary care centers in United Kingdom and Poland between 1999 and 2012. We constructed tissue microarrays, which were stained and scored for 10 biomarkers. We then undertook multivariable regression of eight clinical parameters and 10 biomarkers on a development cohort of 600 patients. Models were validated on an independent, retrospectively collected, 385-patient cohort. RESULTS: A total of 985 subjects (median follow-up 5.03 years, range: 4.73-5.21 years) were included. The final biomarker classifier, comprising p16 and survivin immunohistochemistry, high-risk human papillomavirus (HPV) DNA in situ hybridization, and tumor-infiltrating lymphocytes, predicted benefit from combined surgery + adjuvant chemo/radiotherapy over primary chemoradiotherapy in the high-risk group [3-year overall survival (OS) 63.1% vs. 41.1%, respectively, HR = 0.32; 95% confidence interval (CI), 0.16-0.65; P = 0.002], but not in the low-risk group (HR = 0.4; 95% CI, 0.14-1.24; P = 0.114). On further adjustment by propensity scores, the adjusted HR in the high-risk group was 0.34, 95% CI = 0.17-0.67, P = 0.002, and in the low-risk group HR was 0.5, 95% CI = 0.1-2.38, P = 0.384. The concordance index was 0.73. CONCLUSIONS: We have developed a prognostic classifier, which also appears to demonstrate moderate predictive ability. External validation in a prospective setting is now underway to confirm this and prepare for clinical adoption.