Notes

Abstracts of the SPCCTV 4D Dreams Something like 20, 28-29 November 2020, Figueira nrrr Foz, Portugal.
These findings extend our current understanding of the higher T2D risk among individuals with low circulating LDL-C, and of the underlying mechanisms, including those responsible for the diabetogenic effect of LDL-C-lowering medications.The COVID-19 pandemic has prompted unprecedented global disruption. For medical schools, this has manifested as examination and curricular restructuring as well as significant changes to clinical attachments. With the available evidence suggesting that medical students' mental health status is already poorer than that of the general population, with academic stress being a chief predictor, such changes are likely to have a significant effect on these students. In addition, there is an assumption that these students are an available resource in terms of volunteerism during a crisis. This conjecture should be questioned; however, as those engaging in such work without sufficient preparation are susceptible to moral trauma and adverse health outcomes. This, in conjunction with the likelihood of future pandemics, highlights the need for 'pandemic preparedness' to be embedded in the medical curriculum.After the initial surge in cases of coronavirus (COVID-19), the outbreak has been managed differently in different countries. In the USA, it has been managed in many different ways between states, cities and even counties. This disparity is slowly becoming more and more pronounced with the advent of antibody testing. Although many argue over the potential merits of antibody testing as an immunity passport to allow the economy to restart, there are other implications that stand at the heart of the bioethical debate that are often overlooked. Particularly with COVID-19, there are many uncertainties and the discourse alone of antibodies presumes misinformation that may outweigh the epidemiological benefits of antibody testing. Although this paper does not seek to eliminate antibody testing, it does highlight the need for appropriate counselling both on a personal level with each patient but on a more global level. This moral standard of appropriate education is key to allowing the continued autonomy needed during this pandemic.The perception of time is critical to adaptive behavior. While prefrontal cortex and basal ganglia have been implicated in interval timing in the seconds to minutes range, little is known about the role of the mediodorsal thalamus (MD), which is a key component of the limbic cortico-basal ganglia- thalamocortical loop. In this study we tested the role of the MD in timing, using an operant temporal production task in male mice. In this task, the expected timing of available rewards is indicated by lever pressing. Inactivation of the MD with muscimol produced rightward shifts in peak pressing on probe trials as well as increases in peak spread, thus significantly altering both temporal accuracy and precision. Optogenetic inhibition of glutamatergic projection neurons in the MD also resulted in similar changes in timing. The observed effects were found to be independent of significant changes in movement. Our findings suggest that the MD is a critical component of the neural circuit for interval timing, without playing a direct role in regulating ongoing performance.Significance StatementThe mediodorsal nucleus of the thalamus (MD) is strongly connected with the prefrontal cortex and basal ganglia, areas which have been implicated in interval timing. Previous work has shown that the MD contributes to working memory and learning of action-outcome contingencies, but its role in behavioral timing is poorly understood. Using an operant temporal production task, we showed that inactivation of the MD significantly impaired timing behavior.Background As rates of neonatal opioid withdrawal are increasing, the need for research to evaluate new treatments is growing. Large heterogeneity exists in health outcomes reported in current literature. Our objective is to develop an evidence-informed and consensus-based core outcome set in neonatal opioid withdrawal syndrome (NOWS-COS) for use in studies and clinical practice. Methods An international multidisciplinary steering committee was established. A systematic review and a 3-round Delphi was performed with open-ended and score-based assessments of the importance of each outcome to inform clinical management of neonatal opioid withdrawal. Interviews were conducted with parents and/or caregivers on outcome importance. Finally, a consensus meeting with diverse stakeholders was held to review all data from all sources and establish a core set of outcomes with definitions. Results The NOWS-COS was informed by 47 published studies, 41 Delphi participants, and 6 parent interviews. There were 63 outcomes evaluated. Final core outcomes include (1) pharmacologic treatment, (2) total dose of opioid treatment, (3) duration of treatment, (4) adjuvant therapy, (5) feeding difficulties, (6) consolability, (7) time to adequate symptom control, (8) parent-infant bonding, (9) duration of time the neonate spent in the hospital, (10) breastfeeding, (11) weight gain at hospital discharge, (12) readmission to hospital for withdrawal, and (13) neurodevelopment. Conclusions We developed an evidence-informed and consensus-based core outcome set. Implementation of this core outcome set will reduce heterogeneity between studies and facilitate evidence-based decision-making. Future research will disseminate all the findings and pilot test the validity of the NOWS-COS in additional countries and populations to increase generalizability and impact.Objectives Assess trends in inpatient acute gastroenteritis (AGE) management across children's hospitals and identify elements of AGE management associated with resource use. Methods We examined inpatient stays for children 6 months to 18 years hospitalized with AGE from 2009 to 2018 using the Pediatric Health Information System database. We characterized demographics, hospital-level resource use (ie, medications, laboratories, and imaging), and outcomes (ie, cost per case, 14-day revisit rates, and length of stay [LOS]). We compared demographic characteristics and resource use between 2009 to 2013 and 2014 to 2018 using χ2 and Wilcoxon rank-sum tests. We grouped hospitals on the basis of 2009 use of each resource and trended use over time using logistic regression. Annual change in mean cost and LOS were estimated by using models of log-transformed data. Results Across 32 354 hospitalizations at 38 hospitals, there was a high use of electrolyte testing (85.4%) and intravenous fluids (84.1%) without substantial changes over time. There were significant reductions in the majority of laboratory, medication, and imaging resources across hospitals over the study period. The most notable reductions were for rotavirus and stool testing. Many hospitals saw a decrease in LOS, with only 3 noting an increased revisit rate. Reductions in cost per case over time were most associated with decreases in imaging, laboratory testing, and LOS. Conclusions Significant variation in resource use for children hospitalized with AGE coupled with high use of resources discouraged in AGE guidelines highlights potential opportunities to improve resource use that may be addressed in future AGE guidelines and quality improvement initiatives.Background IFNγ is a pleiotropic cytokine that plays critical immunomodulatory roles in intercellular communication in innate and adaptive immune responses. Despite recognition of IFNγ signaling effects on host defense against viral infection and its utility in immunotherapy and tumor progression, the roles of genetic variants of the IFNγ signaling pathway genes in survival of patients with cancer remain unknown. Methods We used a discovery genotyping dataset from the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial (n = 1,185) and a replication genotyping dataset from the Harvard Lung Cancer Susceptibility Study (n = 984) to evaluate associations between 14,553 genetic variants in 150 IFNγ pathway genes and survival of non-small cell lung cancer (NSCLC). Results The combined analysis identified two independent potentially functional SNPs, ELP2 rs7242481G>A and PIAS1 rs1049493T>C, to be significantly associated with NSCLC survival, with a combined HR of 0.85 (95% confidence interval, 0.78-0.92; P less then 0.0001) and 0.87 (0.81-0.93; P less then 0.0001), respectively. Expression quantitative trait loci analyses showed that the survival-associated ELP2 rs7242481A allele was significantly associated with increased mRNA expression levels of elongator acetyltransferase complex subunit 2 (ELP2) in 373 lymphoblastoid cell lines and 369 whole-blood samples. The PIAS1 rs1049493C allele was significantly associated with decreased mRNA expression levels of PIAS1 in 383 normal lung tissues and 369 whole-blood samples. Conclusions Genetic variants of IFNγ signaling genes are potential prognostic markers for NSCLC survival, likely through modulating the expression of key genes involved in host immune response. Impact Once validated, these variants could be useful predictors of NSCLC survival.The impact of HER2 status in ductal carcinoma in situ (DCIS) on the risk of progression to invasive ductal carcinoma (IDC) has been debated. We aim to use a national database to identify patients with known HER2 status to elucidate the effect of HER2 overexpression on ipsilateral IDC (iIDC) development. We performed survival analysis on patient-level data using the US National Cancer Institute's Surveillance, Epidemiology, and End Results program. We identified patients diagnosed with DCIS who underwent lumpectomy and had known HER2 status. Competing risks analysis was performed. 1,540 patients had known HER2 status and met inclusion criteria. Median age at diagnosis was 60, median follow-up time was 44.5 months. 417 (27.1%) patients were HER2 positive and 1,035 (67.2%) were HER2 negative. 22 (1.4%) patients developed iIDC and 27 (1.8%) developed ipsilateral in situ or contralateral disease. The estimated cumulative incidence of iIDC at 5 years was 1.9% for all patients, 1.2% for HER2 negative and borderline patients, and 3.9% for HER2 positive patients. On multivariate competing risks regression, two factors were significant for iIDC radiation (protective) therapy within 24 months (HR=0.05, p=0.00006) and HER2 overexpression (increased likelihood) (HR=2.72, p=0.044). Patients with HER2 positive DCIS were more likely to have recurrences with receptor discordance. HER2 may serve as a prognostic factor for invasive recurrence and was the only lesion-related factor to significantly relate to iIDC development. It may also be associated with receptor discordance of recurrences. Further large studies will be needed to confirm these results.Many people are diagnosed with cancer after presenting with signs and symptoms of their disease to a healthcare provider. Research from developed countries suggests that, in addition to indicating later-stage disease, symptoms can also indicate earlier-stage disease, leading to investment in research and quality improvement efforts in the early detection of symptomatic cancers. This approach, labelled early diagnosis of symptomatic cancers, focuses on identifying cancer at the earliest possible stage in patients with potential signs and symptoms of cancer, and subsequently diagnosing and treating the cancer without delay. In the United States, early detection has focused on cancer screening, with relatively less research focused on early diagnosis of symptomatic cancers. In this commentary, we propose that research focused on early diagnosis of symptomatic cancers provides an important opportunity to achieve more earlier-stage cancer diagnoses in the US. We highlight the potential of these efforts to improve cancer outcomes, and outline a research agenda to improve early diagnosis of symptomatic cancers in the US focused on defining and describing pathways to cancer diagnosis, identifying signs and symptoms that can be used to promote early cancer detection, and developing interventions to improve early diagnosis of symptomatic cancers.
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