Phenotypic modulation of vascular smooth muscle cells (SMC) is essential for the development of intimal hyperplasia. Lysophosphatidic acid (LPA) is a serum component that can promote phenotypic modulation of cultured SMC, but an endogenous role for this bioactive lipid as a regulator of SMC function in vivo has not been established. Ligation injury of the carotid artery in mice increased levels in the vessel of both autotaxin, the lysophospholipaseD enzyme responsible for generation of extracellular LPA, and two LPA responsive G-protein coupled receptors 1 (LPA1) and 2 (LPA2). LPA1-/-2-/- mice were partially protected from the development of injury-induced neointimal hyperplasia, whereas LPA1-/- mice developed larger neointimal lesions after injury. Growth in serum, LPA-induced ERK activation, and migration to LPA and serum were all attenuated in SMC isolated from LPA1-/-2-/- mice. In contrast, LPA1-/- SMCs exhibited enhanced migration resulting from an upregulation of LPA3. However, despite their involvement in intimal hyperplasia, neither LPA1 nor LPA2 were required for dedifferentiation of SMC following vascular injury or dedifferentiation of isolated SMC in response to LPA or serum in vitro. Similarly, neither LPA1 nor LPA2 were required for LPA to elicit a transient increase in blood pressure following intravenous administration of LPA to mice. These results identify a role for LPA and two defined LPA receptors in regulating SMC migratory responses in the context of vascular injury, but suggest that additional LPA receptor subtypes are required for other LPA-mediated effects in the vasculature.

With the recent increase in complex coronary interventions including percutaneous coronary intervention (PCI) for chronic total occlusions and complex higher risk (and indicated) patients, the spectrum of potential periprocedural complications and their prompt management has become even more relevant. Vascular access-related problems remain the most prevalent of all PCI complications and with randomized controlled trial data from over 20,000 patients supporting the superiority of radial over femoral access in reducing bleeding and vascular complications, a default radial strategy should be promoted. The European Society of Cardiology guidelines have acknowledged this by giving a class 1 (level of evidence: A) recommendation for a radial approach for PCI. The US society guidelines, however, have thus far lagged behind. Each individual patient undergoing a PCI should be risk-stratified objectively using available risk prediction models based on patient comorbidities and anatomical and procedural complexities. Customized informed consent should therefore be provided to all patients and should include the potential risks from radiation injury. Here, we review the current data related to common periprocedural complications related to PCI.

Objectives/Hypothesis Assess the risks and benefits of adenotonsillectomy (AT) for obstructive sleep apnea (OSA) in children with cerebral palsy (CP). Study Design Systematic review. Methods We conducted a systematic review of Medline, Embase, and Cochrane Central Registry from 1946 to 2021. Broad search concepts included cerebral palsy, pediatric, tonsillectomy/adenoidectomy, and sleep. Additional articles were identified by searching reference lists. Studies on the safety and efficacy of AT for OSA management in children with CP were included. Results Fifteen articles met inclusion criteria. Articles were classified into one or more of four themes: intraoperative risk (n = 1), postoperative risk (n = 3), postoperative care requirements (n = 6), and surgical outcomes (n = 7). No intraoperative anesthetic complications were reported. Postoperatively, respiratory complications including pneumonia were common and necessitated additional airway management. Following AT, children with CP required close postoperative observation, experienced increased lengths of stay, and had increased odds of unplanned intensive care unit (ICU) admission. Benefits following AT were improvement in OSA as measured by a reduction in obstructive apnea‐hypopnea index (OAHI) as well as improved quality of life in some; however, many patients went on to require tracheostomy due to persistent OSA. Conclusions Children with CP who undergo AT have a significant risk of developing a postoperative respiratory complication. Realistic counseling of families around increased perioperative risks in this population is imperative and close postoperative monitoring is critical. Many children will obtain a reduction in OAHI, but additional surgical management is often required, including tracheostomy. Further research is needed to determine the best management strategy for OSA in children with CP. Laryngoscope, 132:687–694, 2022

Restrictions imposed by the COVID-19 pandemic have required medical educators to reimagine almost every aspect of undergraduate medical training, including curriculum delivery and assessments in a short timeline. In this personal view article, executive members of the University of Toronto medical student government and Faculty leads of pre-clerkship and clerkship education highlight five practical ways in which a student-Faculty partnership enabled the rapid and smooth adaptation of curricula during the COVID-19 pandemic. These included involving students as partners in decision making to contribute learner perspectives early, agile and collaborative meeting structures, frequent and consistent communication with the student body, providing learners with Faculty perspectives from the frontlines, and striking a balance in the level of feedback collected from students. These strategies may be of utility to medical administrators, educators, and student leaders in future crises affecting medical learners.

Background Superficial parotidectomy has a potential to be performed as an outpatient procedure. The objective of the study is to evaluate the safety and selection profile of outpatient superficial parotidectomy compared to inpatient parotidectomy. Methods A retrospective review of individuals who underwent superficial parotidectomy between 2006 and 2016 at a tertiary care center was conducted. Primary outcomes included surgical complications, including transient/permanent facial nerve palsy, wound infection, hematoma, seroma, and fistula formation, as well as medical complications in the postoperative period. Secondary outcome measures included unplanned emergency room visits and readmissions within 30 days of operation due to postoperative complications. Results There were 238 patients included (124 in outpatient and 114 in inpatient group). There was no significant difference between the groups in terms of gender, co-morbidities, tumor pathology or tumor size. There was a trend towards longer distance to the hospital from home address (111 Km in inpatient vs. 27 in outpatient, mean difference 83 km [95% CI,- 1 to 162 km], p = 0.053). The overall complication rates were comparable between the groups (24.2% in outpatient group vs. 21.1% in inpatient, p = 0.56). There was no difference in the rate of return to the emergency department (3.5% vs 5.6%, p = 0.433) or readmission within 30 days (0.9% vs 0.8%, p = 0.952). Conclusion Superficial parotidectomy can be performed safely as an outpatient procedure without elevated risk of complications. Graphical abstract

The regulated secretory pathway is a specialized form of protein secretion found in endocrine and neuroendocrine cell types. Pro-opiomelanocortin (POMC) is a pro-hormone that utilizes this pathway to be trafficked to dense core secretory granules (DCSGs). Within this organelle, POMC is processed to multiple bioactive hormones that play key roles in cellular physiology.However, the complete set of cellular membrane trafficking proteins that mediate the correct sorting of POMC to DCSGs remain unknown. Here, we report the roles of the phosphofurin acidic cluster sorting protein -1 (PACS-1) and the clathrin adaptor protein 1 (AP-1) in the targeting of POMC to DCSGs. Upon knockdown of PACS-1 and AP-1, POMC is readily secreted into the extracellular milieu and fails to be targeted to DCSGs.

Cardiac troponin assays have become an indispensable tool in the diagnosis of acute myocardial infarction (MI). However, asymptomatic patients with chronic kidney disease often exhibit elevated levels of cardiac troponins with near ubiquitous detection using the new high-sensitive assays. This poses a challenge to physicians faced with differentiating between acute MI and a noncardiac etiology of chest pain or equivalent. Rather than rely on absolute cutoffs it is necessary to follow trends in levels at least over several hours. Even in the absence of an acute MI there is an association between chronic elevations of these biomarkers, underlying structural heart disease and poor prognosis. Although in the chronic setting the underlying cause of cardiac troponin elevation is likely a combination of factors, it should prompt further investigation for modifiable risk factors.

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