SCANPatient: study protocol for a multi-centre, batched, stepped wedge, comparative effectiveness, randomised clinical trial of synoptic reporting of computerised tomography (CT) scans assessing cancers of the pancreas.

BACKGROUND: Complete surgical removal of pancreatic ductal adenocarcinoma (PDAC) is central to all curative treatment approaches for this aggressive disease, yet this is only possible in patients technically amenable to resection. Hence, an accurate assessment of whether patients are suitable for surgery is of paramount importance. The SCANPatient trial aims to test whether implementing a structured synoptic radiological report results in increased institutional accuracy in defining surgical resectability of non-metastatic PDAC. METHODS: SCANPatient is a batched, stepped wedge, comparative effectiveness, cluster randomised clinical trial. The trial will be conducted at 33 Australian hospitals all of which hold regular multi-disciplinary team meetings (MDMs) to discuss newly diagnosed patients with PDAC. Each site is required to manage a minimum of 20 patients per year (across all stages). Hospitals will be randomised to begin synoptic reporting within a batched, stepped wedge design. Initially all hospitals will continue to use their current reporting method; within each batch, after each 6-month period, a randomly selected group of hospitals will commence using the synoptic reports, until all hospitals are using synoptic reporting. Each hospital will provide data from patients who (i) are aged 18 or older; (ii) have suspected PDAC and have an abdominal CT scan, and (iii) are presented at a participating MDM. Non-metastatic patients will be documented as one of the following categories: (1) locally advanced and surgically unresectable; (2) borderline resectable; or (3) anatomically clearly resectable (Note: Metastatic disease is treated as a separate category). Data collection will last for 36 months in each batch, and a total of 2400 patients will be included. DISCUSSION: Better classifying patients with non-metastatic PDAC as having tumours that are either clearly resectable, borderline or locally advanced and unresectable may improve patient outcomes by optimising care and treatment planning. The borderline resectable group are a small but important cohort in whom surgery with curative intent may be considered; however, inconsistencies with definitions and an understanding of resectability status means these patients are often incorrectly classified and hence overlooked for curative options. TRIAL REGISTRATION: The SCANPatient trial was registered on 17th May 2023 in the Australian New Zealand Clinical Trials Registry (ANZCTR) (ACTRN12623000508673).

Predictors of Criminal Sentiments Scale-Modified Scores in Outpatients with Legal System Involvement.

The Criminal Sentiments Scale-Modified (CSS-M) has been widely used as a measure of criminal attitudes. This analysis examined CSS-M scores in a large sample of outpatients with serious mental illnesses and a criminal legal system history. We compared total and subscale scores in our sample to scores from two other previously published U.S. studies in which the CSS-M was used, and evaluated associations between total CSS-M score and nine variables (age, educational attainment, gender, race, marital status, employment status, diagnostic category, substance use disorder comorbidity, and adverse childhood experiences (ACE) score). Scores were higher than in two prior U.S. studies involving other types of samples. Independently significant predictors of higher CSS-M scores included being younger (P < .001), having a higher ACE score (P < .001), being male (P = 03), not identifying as White (P < 001), not having a psychotic disorder (P < 001), and having a comorbid substance use disorder (P = 002). Future research should test the hypothesis that these factors increase risk for arrest and that arrest events, and subsequent criminal legal system involvement, are characterized by negative experiences and perceptions of poor procedural justice, which in turn underpin the negative opinions referred to as "criminal sentiments" or criminal attitudes.

Chest x-ray has low sensitivity to detect silicosis in artificial stone benchtop industry workers.

BACKGROUND AND OBJECTIVE: Chest x-ray (CXR) remains a core component of health monitoring guidelines for workers at risk of exposure to crystalline silica. There has however been a lack of evidence regarding the sensitivity of CXR to detect silicosis in artificial stone benchtop industry workers. METHODS: Paired CXR and high-resolution computed tomography (HRCT) images were acquired from 110 artificial stone benchtop industry workers. Blinded to the clinical diagnosis, each CXR and HRCT was independently read by two thoracic radiologists from a panel of seven, in accordance with International Labour Office (ILO) methodology for CXR and International Classification of HRCT for Occupational and Environmental Respiratory Diseases. Accuracy of screening positive (ILO major category 1, 2 or 3) and negative (ILO major category 0) CXRs were compared with identification of radiological features of silicosis on HRCT. RESULTS: CXR was positive for silicosis in 27/110 (24.5%) workers and HRCT in 40/110 (36.4%). Of the 83 with a negative CXR (ILO category 0), 15 (18.1%) had silicosis on HRCT. All 11 workers with ILO category 2 or 3 CXRs had silicosis on HRCT. In 99 workers ILO category 0 or 1 CXRs, the sensitivity of screening positive CXR compared to silicosis identified by HRCT was 48% (95%CI 29-68) and specificity 97% (90-100). CONCLUSION: Compared to HRCT, sensitivity of CXR was low but specificity was high. Reliance on CXR for health monitoring would provide false reassurance for many workers, delay management and underestimate the prevalence of silicosis in the artificial stone benchtop industry.

Delayed diagnosis of Swyer-James-MacLeod syndrome.

Swyer-James-MacLeod Syndrome is a rare obliterative lung disease typically caused by childhood infection resulting in arrested pulmonary development. Imaging findings include unilateral hyperlucency on chest x-ray, and hyperlucency, hypovascularity and expiratory gas trapping on computed tomography. Recognition of abnormal imaging can lead to earlier diagnosis and institution of appropriate management.

A novel type-2 innate lymphoid cell-based immunotherapy for cancer.

Cell-based cancer immunotherapy has achieved significant advancements, providing a source of hope for cancer patients. Notwithstanding the considerable progress in cell-based immunotherapy, the persistently low response rates and the exorbitant costs associated with their implementation still present a formidable challenge in clinical settings. In the landscape of cell-based cancer immunotherapies, an uncharted territory involves Type 2 innate lymphoid cells (ILC2s) and interleukin-33 (IL-33) which promotes ILC2 functionality, recognized for their inherent ability to enhance immune responses. Recent discoveries regarding their role in actuating cytolytic T lymphocyte responses, including curbing tumor growth rates and hindering metastasis, have added a new dimension to our understanding of the IL-33/ILC2 axis. These recent insights may hold significant promise for ILC2 cell-based immunotherapy. Nevertheless, the prospect of adoptively transferring ILC2s to confer immune protection against tumors has yet to be investigated. The present study addresses this hypothesis, revealing that ILC2s isolated from the lungs of tumor-bearing mice, and tumor infiltrating ILC2s when adoptively transferred after tumor establishment at a ratio of one ILC2 per sixty tumor cells, leads to an influx of tumor infiltrating CD4+ and CD8+ T lymphocytes as well as tumor infiltrating eosinophils resulting in a remarkable reduction in tumor growth. Moreover, we find that post-adoptive transfer of ILC2s, the number of tumor infiltrating ILC2s is inversely proportional to tumor size. Finally, we find corollaries of the IL-33/ILC2 axis enhancing the infiltration of eosinophils in human prostate carcinomas patients' expressing high levels of IL-33 versus those expressing low levels of IL-33. Our results underscore the heightened efficacy of adoptively transferred ILC2s compared to alternative approaches, revealing an approximately one hundred fifty-fold superiority on a cell-per-cell basis over CAR T-cells in the specific targeting and elimination of tumors within the same experimental model. Overall, this study demonstrates the functional significance of ILC2s in cancer immunosurveillance and provides the proof of concept of the potential utility of ILC2 cell-based cancer immunotherapies.

Curcuphenol possesses an unusual histone deacetylase enhancing activity that counters immune escape in metastatic tumours.

Curcuphenol, a common component of the culinary spices, naturally found in marine invertebrates and plants, has been identified as a novel candidate for reversing immune escape by restoring expression of the antigen presentation machinery (APM) in invasive cancers, thereby resurrecting the immune recognition of metastatic tumours. Two synthetic curcuphenol analogues, were prepared by informed design that demonstrated consistent induction of APM expression in metastatic prostate and lung carcinoma cells. Both analogues were subsequently found to possess a previously undescribed histone deacetylase (HDAC)-enhancing activity. Remarkably, the H3K27ac ChIPseq analysis of curcuphenol-treated cells reveals that the induced epigenomic marks closely resemble the changes in genome-wide pattern observed with interferon-γ, a cytokine instrumental for orchestrating innate and adaptive immunity. These observations link dietary components to modifying epigenetic programs that modulate gene expression guiding poised immunity.

A novel cell-based screen identifies chemical entities that reverse the immune-escape phenotype of metastatic tumours.

Genetic and epigenetic events have been implicated in the downregulation of the cellular antigen processing and presentation machinery (APM), which in turn, has been associated with cancer evasion of the immune system. When these essential components are lacking, cancers develop the ability to subvert host immune surveillance allowing cancer cells to become invisible to the immune system and, in turn, promote cancer metastasis. Here we describe and validate the first high-throughput cell-based screening assay to identify chemical extracts and unique chemical entities that reverse the downregulation of APM components in cell lines derived from metastatic tumours. Through the screening of a library of 480 marine invertebrate extracts followed by bioassay-guided fractionation, curcuphenol, a common sesquiterpene phenol derived from turmeric, was identified as the active compound of one of the extracts. We demonstrate that curcuphenol induces the expression of the APM components, TAP-1 and MHC-I molecules, in cell lines derived from both metastatic prostate and lung carcinomas. Turmeric and curcumins that contain curcuphenol have long been utilized not only as a spice in the preparation of food, but also in traditional medicines for treating cancers. The remarkable discovery that a common component of spices can increase the expression of APM components in metastatic tumour cells and, therefore reverse immune-escape mechanisms, provides a rationale for the development of foods and advanced nutraceuticals as therapeutic candidates for harnessing the power of the immune system to recognize and destroy metastatic cancers.

Crisis Response Model Preferences of Mental Health Care Clients With Prior Misdemeanor Arrests and of Their Family and Friends.

The overrepresentation of people with serious mental illnesses in the criminal legal system has spurred the development of crisis response models to improve or reduce police response to a mental health crisis. However, limited research has explored preferences for crisis response, and no research in the United States has examined the responses desired by mental health care clients or their family members. This study aimed to understand the experiences of people with serious mental illnesses interacting with police and to learn about their preferences for crisis response models. The authors interviewed 50 clients with serious mental illnesses and a history of arrest who were enrolled in a randomized controlled trial of a police-mental health linkage system, as well as 18 of their family members and friends. Data were coded with deductive and inductive approaches and were grouped into larger themes. Clients and family or friends described needing a calm environment and empathy during a crisis. They selected a nonpolice response as their first choice and response from a crisis intervention team as their last choice among four options, highlighting the importance of trained responders and past negative interactions with police. However, they also noted concerns about safety and the shortcomings of a nonpolice response. These findings build understanding about clients' and family members' preferences for crisis response and highlight concerns that are relevant for policy makers.

Online education for safer opioid prescribing in hospitals-lessons learnt from the Opioid Use Change (OUCh) project.

BACKGROUND: Opioids are often required for acute inpatient pain relief but lack of knowledge about common and less common long-term side effects can lead to inappropriate discharge prescribing. There are few validated educational tools available for junior prescribers on hospital wards. Education around opioid prescribing and deprescribing remains limited in the undergraduate curriculum and yet almost all controlled drug prescribing in hospitals is done by junior doctors. METHODS: A 5-minute video was developed with iterative feedback from medical students, junior prescribers, pain specialists, primary care educational leads, and a patient who had developed opioid addiction after hospital prescribing. It explained the need for clear stop dates on discharge summaries and the range of opioid side effects. It also highlighted the hospital admission as an opportunity to reduce inappropriate high-dose opioids. A short knowledge-based quiz before and after viewing the video was used to evaluate the impact on and change in knowledge and confidence around opioid prescribing. This tool was designed to be used entirely online to allow delivery within existing mandatory training. RESULTS: Feedback was positive and showed that knowledge of side effects significantly increased but also contacts with ward pharmacists and the acute pain team increased. Junior doctors highlighted that the undergraduate curriculum did little to prepare them for prescription addiction and that pharmacy and senior support was needed to support any changes in longer-term, high-dose opioids. CONCLUSIONS: This short educational video improved knowledge of safe opioid prescribing and could be incorporated within wider opioid education in UK healthcare.

Opening Doors to Recovery: A Randomized Controlled Trial of a Recovery-Oriented Community Navigation Service for Individuals With Serious Mental Illnesses and Repeated Hospitalizations.

Objective: Opening Doors to Recovery (ODR) is a community navigation and recovery support model created in southeast Georgia by diverse, collaborative stakeholders. Following promising results from a quasi-experimental study, this randomized controlled trial hypothesized that, among patients with serious mental illnesses being discharged from inpatient psychiatric settings, compared to those randomized to traditional case management (CM) services, those randomized to ODR would have (1) lower likelihood of hospitalization, fewer hospitalizations, and fewer inpatient days; (2) lower likelihood of arrest, fewer arrests, and longer time to arrest; and, secondarily, (3) greater housing satisfaction and housing stability; and (4) higher scores on several scales measuring recovery-related constructs.Methods: 240 individuals with Structured Clinical Interview for DSM-5 Disorders-based psychotic or mood disorders, functional impairment, and repeated hospitalizations were randomized (December 2014 to June 2018) to ODR or CM. Hospitalization and arrest data were collected from State agencies after 12 months, and housing- and recovery-related measures were collected in person, longitudinally at 4, 8, and 12 months. Intention-to-treat analyses were conducted. Effects of dropout were accounted for, and sensitivity analyses were run.Results: ODR was associated with fewer days hospitalized (RR = 0.86, P = .001), a lower incidence of arrests (OR = 0.35, P < .0005), and longer time to arrest (HR = 0.42, P = .001). In addition, measures of housing satisfaction (Cohen d = 0.45) and recovery (Cohen d = 0.33) were significantly more improved in ODR patients compared to CM patients.Conclusions: The ODR model appears to have advantages over more traditional CM services and could fill a gap in the service array. Studying the mediators of success, cost benefit, dissemination, fidelity, and financing of the model is warranted.Trial Registration: ClinicalTrials.gov identifier: NCT04612777.

Cytomegalovirus infection reduced CD70 expression, signaling and expansion of viral specific memory CD8+ T cells in healthy human adults.

BACKGROUND: Cytomegalovirus (CMV) infection leads to effector memory CD8+ T cell expansion and is associated with immune dysfunction in older adults. However, the molecular alterations of CMV-specific CD8+ T cells in CMV infected healthy young and middle-aged adults has not been fully characterized. RESULTS: We compared CD8+ T cells specific for a CMV epitope (pp65495-503, NLV) and an influenza A virus (IAV) epitope (M158-66, GIL) from the same young and middle-aged healthy adults with serum positive for anti-CMV IgG. Compared to the IAV-specific CD8+ T cells, CMV-specific CD8+ T cells contained more differentiated effector memory (TEM and TEMRA) cells. Isolated CMV-specific central memory (TCM) but not naïve (TN) cells had a significant reduced activation-induced expansion in vitro compared to their IAV-specific counterparts. Furthermore, we found that CD70 expression was reduced in CMV-specific CD28+CD8+ TCM and that CD70+ TCM had better expansion in vitro than did CD70- TCM. Mechanistically, we showed that CD70 directly enhanced MAPK phosphorylation and CMV-specific CD8+ TCM cells had a reduced MAPK signaling upon activation. Lastly, we showed that age did not exacerbate reduced CD70 expression in CMV- specific CD8+ TCM cells. CONCLUSION: Our findings showed that CMV infection causes mild expansion of CMV-NLV-specific CD8+ T cells, reduced CD70 expression and signaling, and proliferation of CMV-NLV-specific CD8+ TCM cells in young and middle-aged healthy adults and revealed an age-independent and CMV infection-specific impact on CD8+ memory T cells.

Quantitative computed tomography predicts outcomes in idiopathic pulmonary fibrosis.

BACKGROUND AND OBJECTIVE: Prediction of disease course in patients with progressive pulmonary fibrosis remains challenging. The purpose of this study was to assess the prognostic value of lung fibrosis extent quantified at computed tomography (CT) using data-driven texture analysis (DTA) in a large cohort of well-characterized patients with idiopathic pulmonary fibrosis (IPF) enrolled in a national registry. METHODS: This retrospective analysis included participants in the Australian IPF Registry with available CT between 2007 and 2016. CT scans were analysed using the DTA method to quantify the extent of lung fibrosis. Demographics, longitudinal pulmonary function and quantitative CT metrics were compared using descriptive statistics. Linear mixed models, and Cox analyses adjusted for age, gender, BMI, smoking history and treatment with anti-fibrotics were performed to assess the relationships between baseline DTA, pulmonary function metrics and outcomes. RESULTS: CT scans of 393 participants were analysed, 221 of which had available pulmonary function testing obtained within 90 days of CT. Linear mixed-effect modelling showed that baseline DTA score was significantly associated with annual rate of decline in forced vital capacity and diffusing capacity of carbon monoxide. In multivariable Cox proportional hazard models, greater extent of lung fibrosis was associated with poorer transplant-free survival (hazard ratio [HR] 1.20, p < 0.0001) and progression-free survival (HR 1.14, p < 0.0001). CONCLUSION: In a multi-centre observational registry of patients with IPF, the extent of fibrotic abnormality on baseline CT quantified using DTA is associated with outcomes independent of pulmonary function.

Deep Learning-based Outcome Prediction in Progressive Fibrotic Lung Disease Using High-Resolution Computed Tomography.

Rationale: Reliable outcome prediction in patients with fibrotic lung disease using baseline high-resolution computed tomography (HRCT) data remains challenging. Objectives: To evaluate the prognostic accuracy of a deep learning algorithm (SOFIA [Systematic Objective Fibrotic Imaging Analysis Algorithm]), trained and validated in the identification of usual interstitial pneumonia (UIP)-like features on HRCT (UIP probability), in a large cohort of well-characterized patients with progressive fibrotic lung disease drawn from a national registry. Methods: SOFIA and radiologist UIP probabilities were converted to Prospective Investigation of Pulmonary Embolism Diagnosis (PIOPED)-based UIP probability categories (UIP not included in the differential, 0-4%; low probability of UIP, 5-29%; intermediate probability of UIP, 30-69%; high probability of UIP, 70-94%; and pathognomonic for UIP, 95-100%), and their prognostic utility was assessed using Cox proportional hazards modeling. Measurements and Main Results: In multivariable analysis adjusting for age, sex, guideline-based radiologic diagnosis, anddisease severity (using total interstitial lung disease [ILD] extent on HRCT, percent predicted FVC, DlCO, or the composite physiologic index), only SOFIA UIP probability PIOPED categories predicted survival. SOFIA-PIOPED UIP probability categories remained prognostically significant in patients considered indeterminate (n = 83) by expert radiologist consensus (hazard ratio, 1.73; P < 0.0001; 95% confidence interval, 1.40-2.14). In patients undergoing surgical lung biopsy (n = 86), after adjusting for guideline-based histologic pattern and total ILD extent on HRCT, only SOFIA-PIOPED probabilities were predictive of mortality (hazard ratio, 1.75; P < 0.0001; 95% confidence interval, 1.37-2.25). Conclusions: Deep learning-based UIP probability on HRCT provides enhanced outcome prediction in patients with progressive fibrotic lung disease when compared with expert radiologist evaluation or guideline-based histologic pattern. In principle, this tool may be useful in multidisciplinary characterization of fibrotic lung disease. The utility of this technology as a decision support system when ILD expertise is unavailable requires further investigation.

A Community Navigation Scale for Persons With Serious Mental Illnesses.

OBJECTIVE: The recovery paradigm in the context of serious mental illnesses pertains to several characteristics of community functioning, adjustment, and integration, among other constructs. Additional rating scales would be beneficial for measuring various facets of community functioning for research that is recovery oriented as opposed to symptom focused. The Community Navigation Scale was developed as part of the Opening Doors to Recovery project to address several aspects of navigating community resources. METHODS: After item development, the 21-item Community Navigation Scale was used across two studies with 340 participants who had serious mental illnesses. Factor analysis revealed three potential factors, and subscales were computed. RESULTS: The social and physical well-being subscale (seven items, Cronbach's α=0.82) addressed community involvement, volunteering, finding enjoyable activities, and engaging in positive health behaviors. The accessing external resources subscale (nine items, Cronbach's α=0.80) tapped one's ability to obtain needed resources, ranging from medications to housing and from small appliances to classes in the community. The home and self-maintenance subscale (five items, Cronbach's α=0.73) measured abilities around shopping, cooking, cell phone use, house cleaning, and personal grooming and hygiene. Initial validity of the subscales was suggested through correlations with the Multnomah Community Ability Scale (r=0.65, 0.55, and 0.41 for social and physical well-being, accessing external resources, and home and self-maintenance, respectively). CONCLUSIONS: The Community Navigation Scale assesses dimensions of community functioning among persons with serious mental illnesses and may add to the array of research and clinical measures pertinent to recovery outcomes. Additional research on its psychometric properties is warranted.

Characterizing Arrests and Charges Among Individuals With Serious Mental Illnesses in Public-Sector Treatment Settings.

Objective: Individuals with serious mental illnesses are overrepresented in all facets of the legal system. State-level criminal histories of patients with serious mental illnesses were analyzed to determine the proportion who had been arrested and number of lifetime arrests and charges, associations of six variables with number of arrests, and the most common charges from individuals' first two arrests and most recent two arrests. Methods: A total of 240 patients were recruited at three inpatient psychiatric facilities and gave consent to access their criminal history. Information was extracted from Record of Arrest and Prosecution (RAP) sheets for lifetime arrests in Georgia. Results: A total of 171 (71%) had been arrested. Their mean±SD lifetime arrests were 8.6±10.1, and mean lifetime charges were 12.6±14.6. In a Poisson regression, number of arrests was associated with lower educational attainment, Black or African American race, the presence of a substance use disorder, the presence of a mood disorder, and female sex. Common early charges included marijuana possession, driving under the influence of alcohol, and burglary and shoplifting. Common recent charges included probation violations, failure to appear in court, officer obstruction­related charges, and disorderly conduct. Conclusions: Findings point to a need for policy and program development in the legal system (e.g., pertaining to charges such as willful obstruction of an officer), the mental health community (e.g., to ensure that professionals know about clients' legal involvement and can partner in strategies to reduce arrests), and social services sectors (to address charges, such as shoplifting, often related to material disadvantage).

PIVET-ED: A Prospective, Randomised, Single-Blinded, Sham Controlled Study of Pelvic Vein Embolisation for Treatment of Erectile Dysfunction.

PURPOSE: Erectile Dysfunction (ED) is defined as the inability to obtain or maintain an erection firm enough for satisfactory sexual performance and affects the quality of life of over 50% of men aged over 40 years. Venogenic ED is elucidated as a cause in a subgroup of patients. The study aims to investigate the clinical success, technical success, safety and durability of venous embolisation for management of venogenic ED. METHODS: After providing informed consent, and subsequent to confirmation of venogenic ED by Doppler ultrasound (dUS) and cavernosography, 80 men referred for cavernosography and pelvic vein embolisation, will undergo randomisation by a computer system either to treatment or sham groups. Efficacy will be assessed using dUS and a validated questionnaire, the International Index of Erectile Function (IIEF). Pharmacologic agents used during the trial will be recorded. The primary outcome of PiVET-ED is to establish clinical success at 3 and 6 months post venous embolisation, as defined by end diastolic velocity in the cavernosal artery < 5 cm/s with dUS and by a > 4-point improvement in IIEF. Durability of the embolisation procedure will be assessed annually to 5 years. Quality of life will be assessed at all study time points using the 36-Item Short Form Survey (SF-36). DISCUSSION: The PiVET-ED trial is a prospective, randomised, single-blinded, single centre, sham controlled study, which aims to establish the safety, efficacy and durability of pelvic vein embolisation for the treatment of venogenic erectile dysfunction. CLINICAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12620001023943, 08/10/2020.

Specific cannabinoids revive adaptive immunity by reversing immune evasion mechanisms in metastatic tumours.

Emerging cancers are sculpted by neo-Darwinian selection for superior growth and survival but minimal immunogenicity; consequently, metastatic cancers often evolve common genetic and epigenetic signatures to elude immune surveillance. Immune subversion by metastatic tumours can be achieved through several mechanisms; one of the most frequently observed involves the loss of expression or mutation of genes composing the MHC-I antigen presentation machinery (APM) that yields tumours invisible to Cytotoxic T lymphocytes, the key component of the adaptive cellular immune response. Fascinating ethnographic and experimental findings indicate that cannabinoids inhibit the growth and progression of several categories of cancer; however, the mechanisms underlying these observations remain clouded in uncertainty. Here, we screened a library of cannabinoid compounds and found molecular selectivity amongst specific cannabinoids, where related molecules such as Δ9-tetrahydrocannabinol, cannabidiol, and cannabigerol can reverse the metastatic immune escape phenotype in vitro by inducing MHC-I cell surface expression in a wide variety of metastatic tumours that subsequently sensitizing tumours to T lymphocyte recognition. Remarkably, H3K27Ac ChIPseq analysis established that cannabigerol and gamma interferon induce overlapping epigenetic signatures and key gene pathways in metastatic tumours related to cellular senescence, as well as APM genes involved in revealing metastatic tumours to the adaptive immune response. Overall, the data suggest that specific cannabinoids may have utility in cancer immunotherapy regimens by overcoming immune escape and augmenting cancer immune surveillance in metastatic disease. Finally, the fundamental discovery of the ability of cannabinoids to alter epigenetic programs may help elucidate many of the pleiotropic medicinal effects of cannabinoids on human physiology.

A 4-tier Protocolized Radiological Classification System for Leaks Following Sleeve Gastrectomy.

OBJECTIVES: To develop and validate a classification of sleeve gastrectomy leaks able to reliably predict outcomes, from protocolized computed tomography (CT) findings and readily available variables. SUMMARY OF BACKGROUND DATA: Leaks post sleeve gastrectomy remain morbid and resource-consuming. Incidence, treatments, and outcomes are variable, representing heterogeneity of the problem. A predictive tool available at presentation would aid management and predict outcomes. METHODS: From a prospective database (2009-2018) we reviewed patients with staple line leaks. A Delphi process was undertaken on candidate variables (80-20). Correlations were performed to stratify 4 groupings based on outcomes (salvage resection, length of stay, and complications) and predictor variables. Training and validation cohorts were established by block randomization. RESULTS: A 4-tiered classification was developed based on CT appearance and duration postsurgery. Interobserver agreement was high (κ = 0.85, P < 0.001). There were 59 patients, (training: 30, validation: 29). Age 42.5 ± 10.8 versus 38.9 ± 10.0 years (P = 0.187); female 65.5% versus 80.0% (P = 0.211), weight 127.4 ± 31.3 versus 141.0 ± 47.9 kg, (P = 0.203). In the training group, there was a trend toward longer hospital stays as grading increased (I = 10.5 d; II = 24 d; III = 66.5 d; IV = 72 d; P = 0.005). Risk of salvage resection increased (risk ratio grade 4 = 9; P = 0.043) as did complication severity (P = 0.027).Findings were reproduced in the validation group: risk of salvage resection (P = 0.007), hospital stay (P = 0.001), complications (P = 0.016). CONCLUSION: We have developed and validated a classification system, based on protocolized CT imaging that predicts a step-wise increased risk of salvage resection, complication severity, and increased hospital stay. The system should aid patient management and facilitate comparisons of outcomes and efficacy of interventions.

The clinical impact of self-reported symptoms of chronic rhinosinusitis in people with bronchiectasis.

BACKGROUND: Chronic rhinosinusitis affects 62% of adults with bronchiectasis and is linked to greater bronchiectasis severity. However, the impact of symptoms of chronic rhinosinusitis on disease-specific and cough-related quality of life is unknown. METHODS: In this cross-sectional study, adults with stable bronchiectasis and chronic rhinosinusitis symptoms completed the sinonasal outcome test-22 (SNOT-22), quality of life-bronchiectasis questionnaire, and Leicester cough questionnaire. Bronchiectasis severity was assessed using the bronchiectasis severity index (BSI) and chest high-resolution computed tomography (HRCT). RESULTS: Sixty participants with bronchiectasis (mean [SD] forced expiratory volume in 1 s of 73.2 [25.5] %predicted) were included. Greater severity of chronic rhinosinusitis symptoms (based on SNOT-22) was moderately associated with impaired cough-related quality of life (according to the Leicester cough questionnaire; all r > -.60) and impaired bronchiectasis-specific quality of life (based on the quality of life-bronchiectasis questionnaire), with impaired physical function (r = -.518), less vitality (r = -.631), reduced social function (r = -.546), greater treatment burden (r = -.411), and increased severity of respiratory symptoms (r = -.534). Chronic rhinosinusitis symptoms were unrelated to disease severity according to the BSI (r = .135) and HRCT scoring (all r < .200). The severity of chronic rhinosinusitis symptoms was not affected by sputum color (p = .417) or the presence of Pseudomonas aeruginosa colonization (p = .73). CONCLUSIONS: In adults with bronchiectasis, chronic rhinosinusitis has a consistent and negative impact on both cough-related and bronchiectasis-specific quality of life.