Linked randomised controlled trials of face-to-face and electronic brief intervention methods to prevent alcohol related harm in young people aged 14–17 years presenting to Emergency Departments (SIPS junior)

Background: Alcohol is a major global threat to public health. Although the main burden of chronic alcohol-related disease is in adults, its foundations often lie in adolescence. Alcohol consumption and related harm increase steeply from the age of 12 until 20 years. Several trials focusing upon young people have reported significant positive effects of brief interventions on a range of alcohol consumption outcomes. A recent review of reviews also suggests that electronic brief interventions (eBIs) using internet and smartphone technologies may markedly reduce alcohol consumption compared with minimal or no intervention controls. Interventions that target non-drinking youth are known to delay the onset of drinking behaviours. Web based alcohol interventions for adolescents also demonstrate significantly greater reductions in consumption and harm among ‘high-risk’ drinkers; however changes in risk status at follow-up for non-drinkers or low-risk drinkers have not been assessed in controlled trials of brief alcohol interventions

Neurosurgical residency adaptations for the residency application cycle amid the COVID-19 pandemic: Acute on chronic sequelae

Background: The COVID-19 pandemic has transformed medical education, including the upcoming residency application cycle. External rotations have been restricted, but virtual opportunities for applicants have not yet been assessed. Objective(s): To describe how neurosurgical residency programs are adapting to the 2021 application cycle through augmented social media usage and establishment of virtual sub-I’s and open houses. Methods: One hundred fifteen separate programs were identified on ERAS. Twitter, Facebook, Instagram, residency websites, and the Visiting Student Application Service (VSAS) were reviewed for virtual open house and sub-I opportunities. Professional neurosurgery society websites were also reviewed. All data is updated as of February 14 th, 2021. Results: Eighty-eight (77%) programs had some social media presence. Fourty-three (30%) departmental accounts were created in 2020. Twenty-four (57%) of the residency program accounts were created in 2020. Programs offered 35 (18%) open house opportunities on Twitter, 19 (17%) on Facebook, and 23 (20%) on Instagram. Nineteen (17%) virtual sub-I opportunities were on Twitter, 9 (8%) on Facebook, and 10 (9%) on Instagram.Virtual opportunities were updated on 13 (12%) residency websites. The National Neurosurgery MedEd website had the most website listings of virtual opportunities with 34 (30%) programs listing open houses and 18 (16%) programs listing virtual sub-I’s. No program specific virtual opportunities were found on the AANS or CNS websites. VSAS identified only 4 (4%) virtual sub-internships. Conclusion: Many neurosurgical residency programs increased their virtual presence amid the COVID-19 pandemic. More programs could utilize these platforms to mitigate applicant restriction in upcoming neurosurgery residency application cycles

Analgesic Efficacy of Quadratus Lumborum Block in Infants Undergoing Pyeloplasty

Post-operative analgesic management is challenging in infants and opioids have been the standard of care. However, they are associated with adverse effects which may negatively impact infants. In this retrospective cohort study, we sought to explore the postoperative analgesic efficacy of quadratus lumborum (QL) block in the infant population undergoing dorsal lumbotomy pyeloplasty. Chart review of 34 infants (≤12 months) who underwent dorsal lumbotomy pyeloplasty between 2016–2020 was performed. Post-operative pain was assessed using externally validated pain scales (CRIES & FLACC) and monitored hemodynamics (pulse and blood pressure). Opioid doses were standardized by using morphine milligram equivalency (MME). The Prescription Database Monitoring Program (PDMP) was utilized to determine if discharge opioid prescriptions were filled. Of 34 patients, 13 received the QL block. Mean age at the time of surgery was 6.2 months ± 3.2 months. The QL group received 0.8 MME postoperatively, whereas the non-QL group received 0.9 MME (p = 0.82). The QL group (20%) filled their discharge opioid prescription less frequently compared to non-QL group (100%) (p = 0.002). There were no observed differences between pain scale or hemodynamic variables. Further studies are warranted to explore QL block’s efficacy for post-operative infant pain management

Translating JAKs to Jakinibs

The discovery of JAKs and STATs and their roles in cytokine and IFN action represented a significant basic advance and a new paradigm in cell signaling. This was quickly followed by discoveries pointing to their essential functions, including identification of mutations as a cause of SCID. This and other findings predicted the use of therapeutically targeting JAKs as a new strategy for treating immune and inflammatory diseases. This now is a reality with seven approved jakinibs being used to treat multiple forms of arthritis, inflammatory bowel disease and myeloproliferative neoplasms, and numerous ongoing clinical trials in other settings. This story provides interesting insights into the process of translating basic discoveries and also reveals the need to return to basic work to fill gaps that now become apparent

Smooth muscle cell surface tissue factor pathway activation by oxidized low-density lipoprotein requires cellular lipid peroxidation

Abstract Tissue factor, which is expressed in vascular lesions, increases thrombin production, blood coagulation, and smooth muscle cell proliferation. We demonstrate that oxidized low-density lipoprotein (LDL) induces surface tissue factor pathway activity (ie, activity of the tissue factor:factor VIIa complex) on human and rat smooth muscle cells. Tissue factor messenger RNA (mRNA) was induced by oxidized LDL or native LDL; however, native LDL did not markedly increase tissue factor activity. We hypothesized that oxidized LDL mediated the activation of the tissue factor pathway via an oxidant-dependent mechanism, because antioxidants blocked the enhanced tissue factor pathway activity by oxidized LDL, but not the increased mRNA or protein induction. We separated total lipid extracts of oxidized LDL using high-performance liquid chromatography (HPLC). This yielded 2 major peaks that induced tissue factor activity. Of the known oxysterols contained in the first peak, 7α- or 7β-hydroxy or 7-ketocholesterol had no effect on tissue factor pathway activity; however, 7β-hydroperoxycholesterol increased tissue factor pathway activity without induction of tissue factor mRNA. Tertiary butyl hydroperoxide also increased tissue factor pathway activity, suggesting that lipid hydroperoxides, some of which exist in atherosclerotic lesions, activate the tissue factor pathway. We speculate that thrombin production could be elevated via a mechanism involving peroxidation of cellular lipids, contributing to arterial thrombosis after plaque rupture. Our data suggest a mechanism by which antioxidants may offer a clinical benefit in acute coronary syndrome and restenosis