Timing of elective surgery and risk assessment after SARS-CoV-2 infection: an update

The impact of vaccination and new SARS-CoV-2 variants on peri-operative outcomes is unclear. We aimed to update previously published consensus recommendations on timing of elective surgery after SARS-CoV-2 infection to assist policymakers, administrative staff, clinicians and patients. The guidance remains that patients should avoid elective surgery within 7 weeks of infection, unless the benefits of doing so exceed the risk of waiting. We recommend individualised multidisciplinary risk assessment for patients requiring elective surgery within 7 weeks of SARS-CoV-2 infection. This should include baseline mortality risk calculation and assessment of risk modifiers (patient factors; SARS-CoV-2 infection; surgical factors). Asymptomatic SARS-CoV-2 infection with previous variants increased peri-operative mortality risk three-fold throughout the 6 weeks after infection, and assumptions that asymptomatic or mildly symptomatic omicron SARS-CoV-2 infection does not add risk are currently unfounded. Patients with persistent symptoms and those with moderate-to-severe COVID-19 may require a longer delay than 7 weeks. Elective surgery should not take place within 10 days of diagnosis of SARS-CoV-2 infection, predominantly because the patient may be infectious, which is a risk to surgical pathways, staff and other patients. We now emphasise that timing of surgery should include the assessment of baseline and increased risk, optimising vaccination and functional status, and shared decision-making. While these recommendations focus on the omicron variant and current evidence, the principles may also be of relevance to future variants. As further data emerge, these recommendations may be revised.     

Selecting the best and brightest: A comparison of residency match processes in the United States and Canada

BACKGROUND:

Selecting candidates for plastic surgery residency training remains a challenge. In the United States, academic measures (United States Medical Licensing Exam Step I scores, medical school class rank and publications) are used as primary criteria for candidate selection for residency. In contrast, Canadian medical education de-emphasizes academic measures by using a pass-fail grading system. As a result, choosing residents from many qualified applicants may pose a challenge for Canadian programs without objective measures of academic success.

METHODS:

A 25-question online survey was distributed to program directors of Canadian plastic surgery residency-training programs. Program directors commented on number of yearly residents and applicants; application sections (ranked in importance using a Likert scale); interview invitation and rank-order list determination; and their satisfaction with the selection process.

RESULTS:

Ten Canadian plastic surgery program directors responded (90.9% response rate). The most important application components determining invitation to interview were letters of reference from a plastic surgeon (mean importance of 5.0 on the Likert scale), clinical electives in plastic surgery (mean 4.6) and electives with their program (mean 4.5). Applicants invited for interview were assessed on the quality of their responses to questions, maturity and personality. The majority of program directors agreed that a clinical elective with their program was important for consideration on their rank-order list. Program directors were neutral on their satisfaction with the selection process.

CONCLUSION:

Canadian plastic surgery residency programs emphasize clinical electives with their program and letters of reference from colleagues when selecting applicants for interviews. In contrast to their American counterparts, Canadian program directors rely on clinical interactions with prospective residents in the absence of objective academic measures.     

Accuracy of Irreversible Hydrocolloid Impression Material Mixed With Disinfectant Solutions

Purpose Irreversible hydrocolloid is capable of resisting contamination by viruses and saliva when the disinfectant iodine or the disinfectant chlorhexidine is added to the water being used to mix the material. This study investigates the accuracy of alginate impressions made with water to which either of the two disinfectants has been added. Materials and Methods A total of 30 casts were made from an impression of a master cast. Ten impressions were made using water according to the manufacturer's instructions, ten were made using water to which iodine had been added, and ten were made using water to which chlorhexidine had been added. A measuring microscope was used to measure three different dimensions on each cast. Each measurement was repeated three times, and the average was used to compute the mean and standard deviation for each measured dimension. The data were statistically evaluated using a one-way analysis of variance. Results There was no statistical difference in the accuracy of irreversible hydrocolloid impressions mixed with water or with either of two disinfectant solutions. Conclusion Accurate casts can be obtained when either of the two disinfectants are incorporated into the alginate impression material.     

Synthetic control of mammalian-cell motility by engineering chemotaxis to an orthogonal bioinert chemical signal

Directed migration of diverse cell types plays a critical role in biological processes ranging from development and morphogenesis to immune response, wound healing, and regeneration. However, techniques to direct, manipulate, and study cell migration in vitro and in vivo in a specific and facile manner are currently limited. We conceived of a strategy to achieve direct control over cell migration to arbitrary user-defined locations, independent of native chemotaxis receptors. Here, we show that genetic modification of cells with an engineered G protein-coupled receptor allows us to redirect their migration to a bioinert drug-like small molecule, clozapine-N-oxide (CNO). The engineered receptor and small-molecule ligand form an orthogonal pair: The receptor does not respond to native ligands, and the inert drug does not bind to native cells. CNO-responsive migration can be engineered into a variety of cell types, including neutrophils, T lymphocytes, keratinocytes, and endothelial cells. The engineered cells migrate up a gradient of the drug CNO and transmigrate through endothelial monolayers. Finally, we demonstrate that T lymphocytes modified with the engineered receptor can specifically migrate in vivo to CNO-releasing beads implanted in a live mouse. This technology provides a generalizable genetic tool to systematically perturb and control cell migration both in vitro and in vivo. In the future, this type of migration control could be a valuable module for engineering therapeutic cellular devices.The ability of many cell types to migrate long distances within the body and specifically localize to target sites of action is critical for their proper function. For example, immune cells rapidly home to sites of infection, concentrating their powerful cytotoxic and proinflammatory activities for maximum efficacy while limiting damage to healthy tissue. In morphogenesis, cells undergo a complex stereotyped process involving migration as well as proliferation, differentiation, and programmed cell death to produce fully developed multicellular structures. In wound healing and regenerative processes, stem and progenitor cells home to injured tissues from nearby sites—as well as from distant locations including the bone marrow—to provide a stream of new cells to replenish and provide trophic support to old and damaged cells.Cell migration is also an important factor to consider in the use of cells as therapeutic agents. The use of cells for the treatment of a growing array of diseases including cancer, autoimmunity, and chronic wounds is currently being explored (1–6). The appropriate and efficient localization of therapeutic cells to sites of disease has been identified as an important factor for successful cell-based therapy (7–17). However, preclinical studies and clinical trials to date have shown that the homing to sites of disease of many cell types commonly used as therapeutics is frequently impaired or limited, especially after ex vivo expansion of cells in culture (7, 12, 18, 19).The ability to redirect the migration of cells to any user-specified location in the body would be a powerful enabling technology for basic research as well as for future applications, but there are currently few easily generalizable strategies to accomplish this goal. We conceived of an approach to direct cellular homing to small molecules by expressing, in motile cells, engineered G protein-coupled receptors (GPCRs) called receptors activated solely by a synthetic ligand (RASSLs) (20, 21).RASSLs are engineered to be unresponsive to endogenous ligands but can be activated by pharmacologically inert orthogonal small molecules (Fig. 1A). Versions of these receptors exist for the three major GPCR signaling pathways (Gαs-, Gαi-, and Gαq-coupled receptors), and the design of a new arrestin-biased variant has recently been reported (21, 22). Because GPCRs control many important physiological functions, including cell migration, we hypothesized that, by expressing these engineered receptors in motile cells, we could develop a general strategy for establishing user control over cell homing (Fig. 1B). Here, we use a family of second-generation RASSLs, known as designer receptors exclusively activated by a designer drug (DREADDs), that are activated only by the small molecule clozapine-N-oxide (CNO), an inert metabolite of the FDA-approved antipsychotic drug clozapine (Fig. S1) (20). CNO is highly bioavailable in rodents and humans, lacks affinity for any known receptors, channels, and transporters, and does not cause any appreciable physiological effects when systemically administered in normal mice (20, 23, 24).Open in a separate windowFig. 1.Engineered Gαi-coupled GPCRs Di3 and Di mediate cytoskeletal changes and chemotaxis of HL-60 neutrophils in response to CNO. (A) RASSLs are engineered GPCRs that interact orthogonally with a bioinert small-molecule drug. Natural ligands do not interact with the engineered receptors, and the bioinert drug that activates the engineered receptors does not interact with native receptors. (B) We tested whether certain second-generation RASSLs known as DREADDs could mediate cell motility. (C) Changes in electrical impedance that result from cell spreading in response to drug or ligand are detected by an electrode array. HL-60 neutrophils transiently transfected to express engineered GPCRs were plated on fibronectin-coated impedance assay plates and stimulated with vehicle control, 100 nM fMLP (positive control chemoattractant) or 100 nM CNO. All cells responded to fMLP whereas only Di3- or Di-expressing cells responded to CNO. Mean ± SEM for n = 3 replicates is shown. (D) Cell migration of HL-60 neutrophils transiently transfected with engineered GPCRs was quantitated in a porous transwell Boyden-chamber assay. All cells migrated in response to fMLP whereas only Di3- or Di-expressing cells migrated in response to CNO. Drug concentrations used: 100 nM CNO, 100 nM fMLP. Mean ± SEM for n = 3 replicates is shown. (E) Polarization and cell migration in neutrophils involves Rac and PI3K activation. Di-expressing HL-60 neutrophils were treated with 100 nM fMLP or 100 nM CNO before immunoblotting for phosphorylated Akt and phosphorylated PAK as readouts for PI3K and Rac activity, respectively. Peak levels of phospho-Akt and phospho-PAK are shown for each condition. Both were increased by CNO stimulation in Di cells but not in control cells (P < 0.01 by Student t test). Stimulation with fMLP increased phospho-Akt and phospho-PAK levels in both Di and control cells (P < 0.01 by Student t test), but Di cells showed higher peak levels of phospho-Akt than did control cells (P < 0.01 by Student t test). Three (for CNO) or four (for fMLP) independent experiments were performed and mean ± SEM are shown.     

Improving organizational and individual performance through coaching: A case study

Organizational change occurs when a critical mass of people within an organization begin to experience one another and the world in which they work differently—a shift of minds.     

USE OF SOLVENTS TO DISPERSE EAR WAX

SUMMARY In this test a course of 4 drops twice a day for 5 days of ear wax solvents, a cerumenolytic, sodium bicarbonate, or sterile water significantly increased the clearance of wax from ears by natural expulsion and eliminated the requirement for ear syringing in 50% of cases.