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The transgenerational maternal effects of polycystic ovary syndrome (PCOS) in female progeny are being revealed. As there is evidence that a male equivalent of PCOS may exists, we ask whether sons born to mothers with PCOS (PCOS-sons) transmit reproductive and metabolic phenotypes to their male progeny. Here, in a register-based cohort and a clinical case-control study, we find that PCOS-sons are more often obese and dyslipidemic. Our prenatal androgenized PCOS-like mouse model with or without diet-induced obesity confirmed that reproductive and metabolic dysfunctions in first-generation (F1) male offspring are passed down to F3. Sequencing of F1–F3 sperm reveals distinct differentially expressed (DE) small non-coding RNAs (sncRNAs) across generations in each lineage. Notably, common targets between transgenerational DEsncRNAs in mouse sperm and in PCOS-sons serum indicate similar effects of maternal hyperandrogenism, strengthening the translational relevance and highlighting a previously underappreciated risk of transmission of reproductive and metabolic dysfunction via the male germline., CC BY 4.0© 2023 The Author(s)Correspondence: qiaolin.deng@ki.se (Q.D.), elisabet.stener-victorin@ki.se (E.S.-V.)We thank Zhiyi Zhao, Jacob Victorin, Sonja Edström, and Sara Pilström for technical assistance during animal work and molecular analysis; TSE Systems and the Metabolic Phenotyping Center at the Strategic Research program in Diabetes at the Karolinska Institutet; and the electron microscopy unit Emil at Huddinge University Hospital at the Karolinska Institutet. This work is supported by the Swedish Medical Research Council: project nos. 2018-02435 and 2022-00550 (E.S.-V.) and 2018-02557 and 2020-00253 (Q.D.); the Knut and Alice Wallenberg Foundation: 2019.0211 (Q.D.); Distinguished Investigator Grant – Endocrinology and Metabolism, Novo Nordisk Foundation: NNF22OC0072904 (E.S.-V.); the Diabetes Foundation:DIA2021-633 (E.S.-V.); the Novo Nordisk Foundation: NNF18OC0033992 and NNF19OC0056647 (E.S.-V.); the Strategic Research Program in Diabetes at the Karolinska Institutet (E.S.-V.); the Adlerbertska Research Foundation: GU 2019/86 (E.S.-V.); Karolinska Institutet KID funding: 2020-00990 (E.S.-V.); a Karolinska Instiutet faculty funded position (Q.D.); the Regional Agreement on Medical Training and Clinical Research between the Stockholm County Council and the Karolinska Institutet: 20190079 (E.S.-V.); O.E. och Edla Johanssons Stiftelse 2021 (S.R.); the Karolinska Institutet China scholarship council program (Q.L.); Magnus Bergvalls Stiftelse: 2020-03808 and 2021-04329 (S.R.); the Karolinska Institutet: 2020-02026 (S.R.); the National Fund for Scientific and Technological Development (FONDECYT): project no. 1151531 (T.S.P.); the FONDECYT: project no. 1201483 (B.E.); the National Commission for Scientific and Technological Research (CONICYT) (R.F.); HKH Kronprinsessan Lovisas förening för barnasjukvård (R.F.); and Stiftelsen Axel Tielmans minnesfond (R.F.)

Background Transcatheter aortic valve replacement (TAVR) is becoming increasingly utilized for the treatment of severe aortic valvular heart disease. Infective endocarditis of TAVR is rare but associated with higher mortality and morbidity. The potential for leaflet thrombosis following TAVR is also becoming increasingly recognized. Diagnosis of these conditions on echocardiography can be challenging due to prosthesis artefact. Case summary An 84-year-old man with a previous transcatheter aortic valve replacement presented with a febrile illness and bacteraemia. Transthoracic and transoesophageal echocardiography demonstrated high transvalvular gradients with features of prosthesis endocarditis, though leaflet morphology could not be fully assessed due to prosthesis artefact. Four-dimensional computed tomography revealed hypo-attenuated leaflet thickening with reduced leaflet motion, consistent with prosthesis leaflet thrombosis. The patient was successfully treated with antibiotics and anticoagulation, with resolution of the infection and normalization of the transvalvular gradient after 6 weeks. Discussion Echocardiography should be the first-line investigation for assessing leaflet morphology in suspected prosthetic valve endocarditis or leaflet thrombosis but its accuracy may be limited by artefact. Our case highlights that fourdimensional computed tomography provides further evaluation of prosthesis leaflet morphology/motion, providing valuable diagnostic information.Copyright © The Author(s) 2020.

Background and objectives: Use of convalescent plasma for coronavirus disease 2019 (COVID-19) treatment has gained interest worldwide. However, there is lack of evidence on its dosing, safety and effectiveness. Until data from clinical studies are available to provide solid evidence for worldwide applicable guidelines, there is a need to provide guidance to the transfusion community and researchers on this emergent therapeutic option. This paper aims to identify existing key gaps in current knowledge in the clinical application of COVID-19 convalescent plasma (CCP). Material(s) and Method(s): The International Society of Blood Transfusion (ISBT) initiated a multidisciplinary working group with worldwide representation from all six continents with the aim of reviewing existing practices on CCP use from donor, product and patient perspectives. A subgroup of clinical transfusion professionals was formed to draft a document for CCP clinical application to identify the gaps in knowledge in existing literature. Result(s): Gaps in knowledge were identified in the following main domains: study design, patient eligibility, CCP dose, frequency and timing of CCP administration, parameters to assess response to CCP treatment and long-term outcome, adverse events and CCP application in less-resourced countries as well as in paediatrics and neonates. Conclusion(s): This paper outlines a framework of gaps in the knowledge of clinical deployment of CPP that were identified as being most relevant. Studies to address the identified gaps are required to provide better evidence on the effectiveness and safety of CCP use.Copyright © 2020 The Authors. Vox Sanguinis published by John Wiley & Sons Ltd on behalf of International Society of Blood Transfusion

Background: Polycystic ovary syndrome (PCOS) is challenging to diagnose. While the 2003 Rotterdam criteria are widely used for adults, the 2018 international PCOS guideline recommended updated Rotterdam criteria with both hyperandrogenism and oligo-anovulation for adolescents based on evidence-informed expert consensus. This study compared the prevalence of PCOS using updated and original Rotterdam criteria in community-based adolescents and explored long-term body mass index (BMI) trajectories across different diagnostic phenotypes. Method(s): Overall, 227 postmenarchal adolescent females from the prospective cohort Raine Study undertook comprehensive PCOS assessment at age 14-16 years. Detailed anthropometric measurements were collected from birth until age 22 years. Cross-sectional and longitudinal BMI were analyzed using t tests and generalized estimating equations. Result(s): PCOS was diagnosed in 66 (29.1%) participants using original criteria versus 37 (16.3%) participants using updated Rotterdam criteria. Using updated criteria, participants with PCOS had higher BMI than participants without PCOS from prepubertal. Only the phenotype meeting the updated criteria was significantly associated with higher long-term BMI gain whereas other PCOS phenotypes had similar BMI trajectories to participants without PCOS (p < 0.001). Conclusion(s): The use of the 2018 updated Rotterdam criteria reduces over-diagnosis of PCOS in adolescents and identifies those at the greatest risk of long-term weight gain, a key contributor to disease severity and long-term health implications. The BMI trajectories of females with PCOS on updated criteria diverge prepubertally compared to those without PCOS. This work supports targeting adolescents diagnosed with PCOS on the 2018 updated criteria for early lifestyle interventions to prevent long-term health complications.Copyright © 2020, The Author(s).

TP53 mutations are implicated in the progression of mucinous borderline tumors (MBOT) to mucinous ovarian carcinomas (MOC). Optimized immunohistochemistry (IHC) for TP53 has been established as a proxy for the TP53 mutation status in other ovarian tumor types. We aimed to confirm the ability of TP53 IHC to predict TP53 mutation status in ovarian mucinous tumors and to evaluate the association of TP53 mutation status with survival among patients with MBOT and MOC. Tumor tissue from an initial cohort of 113 women with MBOT/MOC was stained with optimized IHC for TP53 using tissue microarrays (75.2%) or full sections (24.8%) and interpreted using established criteria as normal or abnormal (overexpression, complete absence, or cytoplasmic). Cases were considered concordant if abnormal IHC staining predicted deleterious TP53 mutations. Discordant tissue microarray cases were re-evaluated on full sections and interpretational criteria were refined. The initial cohort was expanded to a total of 165 MBOT and 424 MOC for the examination of the association of survival with TP53 mutation status, assessed either by TP53 IHC and/or sequencing. Initially, 82/113 (72.6%) cases were concordant using the established criteria. Refined criteria for overexpression to account for intratumoral heterogeneity and terminal differentiation improved concordance to 93.8% (106/113). In the expanded cohort, 19.4% (32/165) of MBOT showed evidence for TP53 mutation and this was associated with a higher risk of recurrence, disease-specific death, and all-cause mortality (overall survival: HR = 4.6, 95% CI 1.5-14.3, p = 0.0087). Within MOC, 61.1% (259/424) harbored a TP53 mutation, but this was not associated with survival (overall survival, p = 0.77). TP53 IHC is an accurate proxy for TP53 mutation status with refined interpretation criteria accounting for intratumoral heterogeneity and terminal differentiation in ovarian mucinous tumors. TP53 mutation status is an important biomarker to identify MB

Introduction: Coronavirus disease 2019 (COVID-19) is a contagious disease that is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Health care workers are at risk of infection from aerosolisation of respiratory secretions, droplet and contact spread. There are a number of procedures that represent a high risk of aerosol generation during cardiothoracic surgery. It is important that adequate training, equipment and procedures are in place to reduce that risk. Recommendations: We provide a number of key recommendations, which reduce the risk of aerosol generation during cardiothoracic surgery and help protect patients and staff. These include general measures such as patient risk stratification, appropriate use of personal protective equipment, consideration to delay surgery in positive patients, and careful attention to theatre planning and preparation. There are also recommended procedural interventions during airway management, transoesophageal echocardiography, cardiopulmonary bypass, chest drain management and specific cardiothoracic surgical procedures. Controversies exist regarding the management of low risk patients undergoing procedures at high risk of aerosol generation, and recommendations for these patients will change depending on the regional prevalence, risk of community transmission and the potential for asymptomatic patients attending for these procedures. Changes in management as a result of this statement: This statement reflects changes in management based on expert opinion, national guidelines and available evidence. Our knowledge with regard to COVID-19 continues to evolve and with this, guidance may change and develop. Our colleagues are urged to follow national guidelines and institutional recommendations regarding best practices to protect their patients and themselves. Endorsed by: Australian and New Zealand Society of Cardiac and Thoracic Surgeons and the Anaesthetic Continuing Education Cardiac Thoracic Vascular a

Purpose: Intravenous iodinated contrast is a commonly used diagnostic aid to improve image quality on computed tomography. There exists a small risk of post-contrast acute kidney injury in patients receiving IV contrast. One of the biggest risk factors for developing PC-AKI is the presence of pre-existing renal dysfunction, making it important to measure the renal function prior to contrast administration. Point of care (POC) devices offer a quick estimation of renal function, potentially improving workflows in radiology departments. Method(s): Two POC devices were evaluated, the Nova StatSensor and Abbott iSTAT. Patients undergoing routine radiological investigations had blood collected and analysed by a POC method and the laboratory method (Beckman AU5800). The two values were analysed and compared. Renal function was calculated using eGFR via the CKD-EPI result. eGFR values were stratified as high risk (eGFR < 30), moderate risk (eGFR 30-59) and low risk (eGFR >= 60). Result(s): One hundred eighty-six patients were included in the study. One hundred one patients underwent the Abbott iSTAT analysis, 139 patients underwent Nova StatSensor analysis, and 53 had both. Statistical analysis revealed that the StatSensor R2 value was 0.77, and coefficient variation was 10.65%. iSTAT had a R2 value of 0.83 and coefficient variation of 7.36%. The POC devices did not miss any high-risk patients but underreported eGFR values in certain patients. Conclusion(s): POC devices are moderately accurate at detecting renal impairment in patients undergoing radiological investigations. They seem to be a good screening tool; however, any low eGFR values should be further examined.Copyright © 2020, American Society of Emergency Radiology.

Background: Using Infliximab early in Crohn's disease can provide a window of opportunity in children for restoration of growth and achievement of puberty. We aimed to compare clinical outcomes and costs of a retrospective pediatric Crohn's disease (pCD) cohort treated with early use Infliximab (EUI) within 12 months compared with later use Infliximab (LUI). Method(s): Retrospective review of all children with pCD commenced on Infliximab was undertaken in a tertiary Australian pediatric center. Result(s): pCD progressing to Infliximab was identified in 70 children: 38 (54%) in the EUI cohort versus 32 (46%) in the LUI cohort. Intestinal surgery had a higher risk of occurring in EUI when compared with LUI (2 (5%) versus 9 (28%), HR 5.67 (95% CI 1.21-26.38); p =.027). No patients in EUI underwent intestinal surgery post Infliximab commencement compared with 3 (9%) in LUI (p =.09). Escalation of Infliximab in luminal Crohn's disease was not significantly different in EUI when compared with LUI (3 (10.3%) versus 9 (39.1%) (p =.1)). EUI was more frequently used than LUI in 2015-2018 (27 (71%) versus 14 (44%)) p =.029, with the inverse occurring in 2010-2014 (11 (29%) versus 18 (56%)). Hospital admissions per person per year in EUI and LUI were 43 (0.23 visits/person/year) versus 84 (0.67 visits/person/year); IRR 2.51 (95% CI 0.9-7.01); p =.078). Health costs were not significantly different between cohorts. Conclusion(s): EUI in pCD is associated with an increased likelihood of being diagnosed in more recent years, less intestinal surgery and a trend toward decreased hospital admissions than LUI.Copyright © 2021 Informa UK Limited, trading as Taylor & Francis Group.

The spread of SARS-CoV-2 infection has increased the risk of mental health problems, including post-traumatic stress disorders (PTSD), and healthcare workers (HCWs) are at greater risk than other occupational groups. This observational cross-sectional study aimed to explore the symptoms of depression, anxiety, and PTSD among dental HCWs in Russia during the coronavirus disease 2019 (COVID-19) pandemic. The survey was carried out among 128 dental HCWs from three dental clinics of Ekaterinburg, Russia. The mean age of the sample was 38.6 years. Depression, anxiety, and stress were assessed using the Depression Anxiety and Stress Scale-21 (DASS-21); PTSD was assessed using the PTSD Symptom Scale-Self-Report (PSS-SR); subjective distress was assessed using the Impact of Event Scale-Revised (IES-R). The results indicated that 20.3-24.2% HCWs had mild to extremely severe symptoms of psychological distress, and 7.1-29.7% had clinical symptoms of PTSD. No differences between females and males were revealed. HCWs working directly with patients had significantly higher levels of PTSD symptoms and the risk of PTSD development compared to those working indirectly, whereas older HCWs had significantly higher levels of both psychological distress and PTSD symptoms compared to younger HCWs. Thus, dental HCWs are at high risk for psychological distress and PTSD symptoms during the COVID-19 pandemic. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.

Simple Summary The main problem encountered in the management of prostate cancer (PCa) is the inability to distinguish slow-growing indolent tumors from aggressive tumors. It is therefore important to explore non-invasive assays for the early detection of this aggressive subtype, when it can still be treated effectively. The presence of the TWEAK cytokine in biofluids of the PCa microenvironment might drive the secretion of extracellular vesicles (EVs) containing exo-oncomicroRNAs capable of modifying the tumor microenvironment. These exo-oncomicroRNAs are potentially useful as PCa biomarkers. We identified 2 exo-oncomiRNAs isolated from semen EVs by the action of TWEAK in the tumor microenvironment and, we determined their usefulness as biomarkers of PCa prognostic. We also established, for the first time, that TWEAK modulates potential exo-oncomiRNA targets, both tightly linked to cancer progression. In conclusion, our study shows that semen detection of TWEAK-regulated exo-oncomiRNAs can improve PCa prognosis, opening new avenues for diagnosis and treatment. Liquid biopsy-based biomarkers, including microRNAs packaged within extracellular vesicles, are promising tools for patient management. The cytokine tumor necrosis factor-like weak inducer of apoptosis (TWEAK) is related to PCa progression and is found in the semen of patients with PCa. TWEAK can induce the transfer of exo-oncomiRNAs from tumor cells to body fluids, and this process might have utility in non-invasive PCa prognosis. We investigated TWEAK-regulated exo-microRNAs in semen and in post-digital rectal examination urine from patients with different degrees of PCa aggressiveness. We first identified 14 exo-oncomiRNAs regulated by TWEAK in PCa cells in vitro, and subsequently validated those using liquid

Background and aims: This European Atherosclerosis Society (EAS) Task Force provides practical guidance for combination therapy for elevated low-density lipoprotein cholesterol (LDL-C) and/or triglycerides (TG) in highrisk and very-high-risk patients. Methods: Evidence-based review. Results: Statin-ezetimibe combination treatment is the first choice for managing elevated LDL-C and should be given upfront in very-high-risk patients with high LDL-C unlikely to reach goal with a statin, and in primary prevention familial hypercholesterolaemia patients. A proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor may be added if LDL-C levels remain high. In high and very-high-risk patients with mild to moderately elevated TG levels (>2.3 and < 5.6 mmol/L [>200 and < 500 mg/dL) on a statin, treatment with either a fibrate or high-dose omega-3 fatty acids (icosapent ethyl) may be considered, weighing the benefit versus risks. Combination with fenofibrate may be considered for both macro- and microvascular benefits in patients with type 2 diabetes mellitus. Conclusions: This guidance aims to improve real-world use of guideline-recommended combination lipid modifying treatment.

Background: Current guidelines favor fistulas over catheters as vascular access. Yet, the observational literature comparing fistulas to catheters has important limitations and biases that may be difficult to overcome in the absence of randomization. However, it is not clear if physicians would be willing to participate in a clinical trial comparing fistulas to catheters. Objective(s): We also sought to elicit participants' opinions on willingness to participate in a future trial regarding catheters and fistulas. Design(s): We created a three-part survey consisting of 19 questions. We collected demographic information, respondents' knowledge of the vascular access literature, appropriateness of current guideline recommendations, and their willingness to participate in a future trial. Setting(s): Participants were recruited from Canada, Europe, Australia, and New Zealand. Participant(s): Participants include physicians and trainees who are involved in the care of end-stage renal disease patients requiring vascular access. Measurements: Descriptive statistics were used to describe baseline characteristics of respondents according to geographic location. We used logistic regression to model willingness to participate in a future trial. Method(s): We surveyed nephrologists from Canada, Europe, Australia, and New Zealand to assess their willingness to participate in a randomized trial comparing fistulas to catheters in incident hemodialysis patients. Result(s): Our results show that in Canada, 86 % of respondents were willing to participate in a trial (32 % in all patients; 54 % only in patients at high risk of primary failure). In Europe and Australia/New Zealand, the willingness to participate in a trial that included all patients was lower (28 % in Europe; 25 % in Australia/New Zealand), as was a trial that included patients at high risk of primary failure (38 % in Europe; 39 % in Australia/New Zealand). Nephrologists who have been in practice for a few years, saw a l

Objective We aimed to review data about delaying strategies for the management of hepatobiliary cancers requir-ing surgery during the covid-19 pandemic. Background Given the covid-19 pandemic, many jurisdictions, to spare resources, have limited access to operating rooms for elective surgical activity, including cancer, thus forcing deferral or cancellation of cancer surgeries. Surgery for hepatobiliary cancer is high-risk and particularly resource-intensive. Surgeons must critically appraise which patients will benefit most from surgery and which ones have other therapeutic options to delay surgery. Little guidance is currently available about potential delaying strategies for hepatobiliary cancers when surgery is not possible. Methods An international multidisciplinary panel reviewed the available literature to summarize data relating to standard-of-care surgical management and possible mitigating strategies to be used as a bridge to surgery for colorectal liver metastases, hepatocellular carcinoma, gallbladder cancer, intrahepatic cholangiocarcinoma, and hilar cholangiocarcinoma. Results Outcomes of surgery during the covid-19 pandemic are reviewed. Resource requirements are summarized, including logistics and adverse effects profiles for hepatectomy and delaying strategies using systemic, percutaneous and radiation ablative, and liver embolic therapies. For each cancer type, the long-term oncologic outcomes of hepatectomy and the clinical tools that can be used to prognosticate for individual patients are detailed. Conclusions There are a variety of delaying strategies to consider if availability of operating rooms decreases. This review summarizes available data to provide guidance about possible delaying strategies depending on patient, resource, institution, and systems factors. Multidisciplinary team discussions should be leveraged to consider patient-and tumour-specific information for each individual case.Copyright © 2020 Multimed Inc.

Introduction: Thyroid nodules are increasingly common. Despite being an essential pre-operative diagnostic tool, up to 30% of fine needle aspirate cytology (FNAC) yields a non-definitive diagnosis. This study aimed to quantify differences in surgical management of patients with definitive and indeterminate thyroid nodule cytology, and determine if clinical factors can improve cytological diagnosis. Material(s) and Method(s): Patients who underwent thyroidectomy for nodules from 2001 to 2015 were recruited. Those with benign and malignant preoperative cytology were included in the "definitive diagnosis" (DC) group; patients with all other preoperative cytology results were included in the "indeterminate diagnosis" (IC) group. We compared demographics and procedures between these groups. Clinical factors and demographics were also compared between patients with benign and malignant histology in the IC group. Result(s): A total of 3821 cases were included. A significantly larger proportion of the IC patients had a hemithyroidectomy (IC 69% vs. DC 39%, p < 0.001) initially, and also had a significantly higher rate of two-stage surgery compared to the DC group (IC 17% vs. DC 11%, p < 0.001). Patients in the DC group were twice as likely to undergo concurrent central lymph node dissection for papillary and medullary cancers than the IC group (p < 0.001). Overall, up to 60% of IC patients had been over- or under-treated at initial surgery. The clinical factors examined were not significantly associated with higher risk of malignancy in IC patients. Conclusion(s): This study highlights the potential for improved preoperative diagnosis to streamline decision making for surgical management of patients with thyroid nodules.Copyright © 2019 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology

Background: Recent single-center studies promote oral penicillin challenges, without skin testing, in patients with low risk/likelihood of true allergy. However, how best to define a low-risk penicillin allergy history is uncertain. Objective(s): To statistically determine an optimal low-risk definition, to select patients for safe outpatient penicillin challenges, without skin testing. Method(s): In a multicenter Australian study (February 2016 to May 2018), testing strategy (skin test and/or oral penicillin challenge) and outcomes were retrospectively collected for all penicillin-allergic patients. Statistical modeling was performed with 8 low-risk definitions, to determine an optimal low-risk definition. Result(s): A total of 447 subjects (mean age, 45.3 years; 63.8% females) were analyzed. A history of benign, immediate, or delayed rash, more than 1 year before review, was the optimal low-risk definition. A total of 244 of 447 (54.6%) patients met this definition, of which 97.1% tolerated a 1- or 2-dose penicillin challenge, with no anaphylaxis in those who reacted. Of 203 patients designated higher risk, 54 (26.6%) had their allergy confirmed by skin test (n = 45) or challenge (n = 9). Conclusion(s): History of penicillin-associated rash (without angioedema, mucosal ulceration, or systemic involvement), more than 1 year ago, is sufficient to select a patient for a direct oral penicillin challenge. This large multicenter study demonstrates that this approach appears safe, and risk is comparable to that in other procedures being performed in primary care in Australia. The higher risk patients are more likely to benefit from skin testing. This simple risk-based delabeling strategy could potentially be used by nonallergists, leading to more efficient penicillin allergy delabeling service provision.Copyright © 2019 American Academy of Allergy, Asthma & Immunology

Background: Three tools are currently available to predict the risk of contralateral breast cancer (CBC). We aimed to compare the performance of the Manchester formula, CBCrisk, and PredictCBC in patients with invasive breast cancer (BC). Method(s): We analyzed data of 132,756 patients (4682 CBC) from 20 international studies with a median follow-up of 8.8 years. Prediction performance included discrimination, quantified as a time-dependent Area-Under-the-Curve (AUC) at 5 and 10 years after diagnosis of primary BC, and calibration, quantified as the expected-observed (E/O) ratio at 5 and 10 years and the calibration slope. Result(s): The AUC at 10 years was: 0.58 (95% confidence intervals [CI] 0.57-0.59) for CBCrisk; 0.60 (95% CI 0.59-0.61) for the Manchester formula; 0.63 (95% CI 0.59-0.66) and 0.59 (95% CI 0.56-0.62) for PredictCBC-1A (for settings where BRCA1/2 mutation status is available) and PredictCBC-1B (for the general population), respectively. The E/O at 10 years: 0.82 (95% CI 0.51-1.32) for CBCrisk; 1.53 (95% CI 0.63-3.73) for the Manchester formula; 1.28 (95% CI 0.63-2.58) for PredictCBC-1A and 1.35 (95% CI 0.65-2.77) for PredictCBC-1B. The calibration slope was 1.26 (95% CI 1.01-1.50) for CBCrisk; 0.90 (95% CI 0.79-1.02) for PredictCBC-1A; 0.81 (95% CI 0.63-0.99) for PredictCBC-1B, and 0.39 (95% CI 0.34-0.43) for the Manchester formula. Conclusion(s): Current CBC risk prediction tools provide only moderate discrimination and the Manchester formula was poorly calibrated. Better predictors and re-calibration are needed to improve CBC prediction and to identify low- and high-CBC risk patients for clinical decision-making.Copyright © 2020, Springer Science+Business Media, LLC, part of Springer Nature.

Background: Patients admitted to hospital with acute heart failure (AHF) are at increased risk of readmission and mortality post-discharge. The aim of the study was to examine health service utilisation within 30 days post-discharge from an AHF hospitalisation. Method(s): This was a prospective, observational, non-randomised study of consecutive patients hospitalised with acute HF to one of 16 Victorian hospitals over a 30-day period each year and followed up for 30 days post-discharge. The project was conducted annually over three consecutive years from 2015 to 2017. Result(s): Of the 1,197 patients, 56.3% were male with an average age of 77+/-13.23 years. Over half of the patients (711, 62.5%) were referred to an outpatient clinic and a third (391, 34.4%) to a HF disease management program. In-hospital mortality was 5.1% with 30 day-mortality of 9% and readmission rate of 24.4%. Patients who experienced a subsequent readmission less than 10 days post-discharge and between 11 and 20 days post-discharge had a five- to six-fold increase in risk of mortality (adjusted OR 5.02, 95% CI 2.11-11.97; OR 6.45, 95% CI 2.69-15.42; respectively) compared to patients who were not readmitted to hospital. An outpatient appointment within 30 days post-discharge significantly reduced the risk of 30-day mortality by 81% (95% CI 0.09-0.43). Conclusion(s): Patients admitted to hospital with AHF who experience a subsequent readmission within 20 days post-discharge are at increased risk of dying. However, early follow-up post-discharge may reduce this risk. Early post-discharge follow-up is vital to address this vulnerable period after a HF admission.Copyright © 2020 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ)

Background: The aim of this systematic review is to examine patient-reported outcome measures (PROMs), their attributes and application in patients with pancreatic cancer (PC). Method(s): A systematic literature search was undertaken of articles published to June 2018 to identify PROMs applied in primary studies in PC. Characteristics of the included studies and PROMs were described with identified scales grouped into five domains. The psychometric properties of the identified PROMs were further assessed for reliability and validity among patients with PC. Result(s): From 1688 studies screened, 170 were included. Almost half (48%) were conducted in patients with unresectable PC; the majority of these (68%) were evaluated in randomized controlled trials. Median questionnaire completion rates fell below 10% of the original cohort within 12 months in patients with unresectable PC compared to 75% in patients with resectable PC. Seventy PROMs were identified, 32 measuring unidimensional parameters (e.g. pain) and 35 measuring multidimensional (e.g. quality of life) constructs. Only five (7%) PROMs were disease-specific and 13 (19%) were validated in patients with PC. Fifty scales were grouped into 19 physical, 9 psychological, 6 psychiatric, 9 social and 7 other domains. Conclusion(s): Three multidimensional PROMs, the: (i) FACT-HEP in unresectable PC; (ii) QLQ-PAN26 (in conjunction with its core QLQ-C30 PROM) in resectable PC; and (iii) MDASI-GI are recommended as instruments to capture quality of life in patients with PC. Summarised scales and psychometric evaluation provide a framework to choose PROMs for scales not captured by the recommended PROMs.Copyright © 2019 International Hepato-Pancreato-Biliary Association Inc.

Background: Serum alkaline phosphatase (ALP) is associated with incident cardiovascular disease (CVD), coronary artery disease, vascular calcification, cerebral small vessel disease and ischemic stroke. Recent studies also associate elevated ALP with impaired cognition, suggesting neuronal or neurovascular dysfunction. To date there is no specific pharmacological means to lower ALP. Bromodomain & extraterminal (BET) proteins bind to acetylated histones on chromatin and regulate gene transcription. Apabetalone (ABET) targets the second bromodomain of BET proteins and inhibits expression of genes that participate in vascular inflammation and calcification, coagulation and the complement pathway. In CVD patients (pts), ABET lowers serum ALP in a dose-dependent manner. Method(s): In phase 2 ABET studies (n=795) up to 26 weeks' duration in CVD pts, we assessed the relationship of ALP and CVD events. In the ongoing phase 3 BETonMACE study with ABET (n=2,425), baseline cognitive function (Montreal Cognitive Assessment, MoCA) and ALP were measured in pts aged 70 yrs and older (n=467). Result(s): In phase 2 studies, CVD events (death, non-fatal MI, coronary revascularization, or hospitalization for CV cause) were lowered by 44% (p=0.02) with ABET. Baseline ALP (median 72 U/L) independently predicted CVD events (hazard ratio [HR] per standard deviation [SD] 1.6, 95% CI 1.2-2.1, p<0.001). Mean ABET decrease in ALP from baseline was 8.45% (p<0.001), or 6.6 U/L. A 1 SD (13.0 U/L) reduction in ALP with ABET was associated with a HR for MACE of 0.58 (95% CI 0.43-0.78, p<0.001). In the BETonMACE trial pts were classified by baseline MoCA >26 (normal, n=221), 21-25 (borderline, n=161), or <21 (impaired, n=85). Pts with impaired cognition had higher ALP (trend p-value 0.006), lower eGFR (66 vs. 71, p=0.04), and higher hsCRP (4.8 vs.1.8, p=0.03). Conclusion(s): Serum ALP is associated with coronary and cerebral vascular disease. ABET is a BET-inhibitor that lowers serum ALP in CVD pts

Although contemporary chronic total occlusion (CTO) percutaneous coronary intervention (PCI) is performed with high success rates, 10% to 13% of patients presenting with CTOs have chronic kidney disease (CKD), and the comparative safety, efficacy, and health status benefit of CTO PCI in these patients, has not been well defined. We examined the association of baseline renal function with periprocedural major adverse cardiovascular and cerebral events and health status outcomes in 957 consecutive patients (mean age 65.3 +/- 10.3 years, 19.4% women, 90.3% white, 23.6 CKD [estimated glomerular filtration rate {eGFR} < 60]) in the OPEN-CTO (Outcomes, Patients Health Status, and Efficiency in Chronic Total Occlusions Registry) study. Hierarchical multivariable regression models were used to examine the independent association of baseline eGFR with technical success, periprocedural complications and change in health status, using Seattle Angina Questionnaire (SAQ) over 1 year. Crude rates of acute kidney injury were higher (13.5% vs 4.4%, p <0.001) and technical success lower (81.8% vs 88.4%, p = 0.01) in patients with CKD. There were no significant differences in other periprocedural complications. After adjustment for confounding factors, there was no significant association of baseline eGFR with technical success or periprocedural major adverse cardiovascular and cerebral events (death, myocardial infarction, emergent bypass surgery, stroke, perforation), whereas patients with lower eGFR had higher rates of acute kidney injury. The difference in SAQ summary score, between patients on the 10th and 90th percentile for baseline eGFR distribution was not clinically significant (1 month: -0.91; 1 year: -3.06 points). In conclusion, CTO PCI success, complication rates, and the health status improvement after CTO PCI are similar in patients across a range of baseline eGFRs.Copyright © 2020 Elsevier Inc.

Background: Conventional imaging using CT and bone scan has insufficient sensitivity when staging men with high-risk localised prostate cancer. We aimed to investigate whether novel imaging using prostate-specific membrane antigen (PSMA) PET-CT might improve accuracy and affect management. Method(s): In this multicentre, two-arm, randomised study, we recruited men with biopsy-proven prostate cancer and high-risk features at ten hospitals in Australia. Patients were randomly assigned to conventional imaging with CT and bone scanning or gallium-68 PSMA-11 PET-CT. First-line imaging was done within 21 days following randomisation. Patients crossed over unless three or more distant metastases were identified. The primary outcome was accuracy of first-line imaging for identifying either pelvic nodal or distant-metastatic disease defined by the receiver-operating curve using a predefined reference-standard including histopathology, imaging, and biochemistry at 6-month follow-up. This trial is registered with the Australian New Zealand Clinical Trials Registry, ANZCTR12617000005358. Finding(s): From March 22, 2017 to Nov 02, 2018, 339 men were assessed for eligibility and 302 men were randomly assigned. 152 (50%) men were randomly assigned to conventional imaging and 150 (50%) to PSMA PET-CT. Of 295 (98%) men with follow-up, 87 (30%) had pelvic nodal or distant metastatic disease. PSMA PET-CT had a 27% (95% CI 23-31) greater accuracy than that of conventional imaging (92% [88-95] vs 65% [60-69]; p<0.0001). We found a lower sensitivity (38% [24-52] vs 85% [74-96]) and specificity (91% [85-97] vs 98% [95-100]) for conventional imaging compared with PSMA PET-CT. Subgroup analyses also showed the superiority of PSMA PET-CT (area under the curve of the receiver operating characteristic curve 91% vs 59% [32% absolute difference; 28-35] for patients with pelvic nodal metastases, and 95% vs 74% [22% absolute difference; 18-26] for patients with distant metastases). First-line conv