Augmented Reality Microsurgery: Proof of Concept for a Novel Approach to Microsurgical Field Visualization in Plastic Surgery.

BACKGROUND: Microsurgery is conducted on tiny anatomical structures such as blood vessels and nerves. Over the past few decades, little has changed in the way plastic surgeons visualize and interact with the microsurgical field. New advances in augmented reality (AR) technology present a novel method for microsurgical field visualization. Voice- and gesture-based commands can be used in real time to adjust the size and position of a digital screen. Surgical decision support and/or navigation may also be used. The authors assess the use of AR in microsurgery. METHODS: The video feed from a Leica Microsystems OHX surgical microscope was streamed to a Microsoft HoloLens2 AR headset. A fellowship-trained microsurgeon and three plastic surgery residents then performed a series of four arterial anastomoses on a chicken thigh model using the AR headset, a surgical microscope, a video microscope (or "exoscope"), and surgical loupes. RESULTS: The AR headset provided an unhindered view of the microsurgical field and peripheral environment. The subjects remarked on the benefits of having the virtual screen track with head movements. The ability of participants to place the microsurgical field in a tailored comfortable, ergonomic position was also noted. Points of improvement were the low image quality compared with current monitors, image latency, and the lack of depth perception. CONCLUSIONS: AR is a useful tool that has the potential to improve microsurgical field visualization and the way surgeons interact with surgical monitors. Improvements in screen resolution, latency, and depth of field are needed.

Comparison of three-weekly and six-weekly pembrolizumab United Kingdom prescribing practice for advanced and resected melanoma.

BACKGROUND: Pembrolizumab is approved for the treatment of advanced and resected melanoma and was originally licensed as a three-weekly infusion (Q3W). In April 2019, a six-weekly infusion schedule (Q6W) was also approved. We retrospectively reviewed pembrolizumab prescribing for patients with melanoma across multiple United Kingdom (UK) centres to compare the safety and efficacy of Q6W with Q3W in real-world clinical practice. METHODS: Case notes for melanoma patients treated with pembrolizumab between April 2019 and August 2020 at eight UK centres were reviewed. Prespecified baseline characteristics of the Q3W and Q6W cohorts were compared, as well as toxicity and efficacy outcomes. Prescribers were surveyed about their prescribing practice. RESULTS: Two hundred seventy-seven patients were included: 116 commenced Q3W and 161 commenced Q6W pembrolizumab. The proportion of Q6W prescriptions varied by the centre (range 32-88%). Patient factors associated with an increased likelihood of receiving Q3W over Q6W were preexisting autoimmune comorbidity (odds ratio [OR] 0.33; 95% confidence interval [CI] 0.12-0.82) and treatment for advanced (versus resected) disease (OR 0.54; 95%CI 0.33-0.90). Toxicity outcomes were broadly similar for Q6W and Q3W: 14.9% versus 15.5% ≥ grade 3 Common Terminology Criteria for Adverse Events. Estimated 12-month recurrence-free survival for adjuvantly treated patients was 78.9% for Q6W and 74.2% for Q3W (hazard ratio [HR] 0.93; 95%CI 0.50-1.73). Estimated 12-month progression-free survival for advanced patients was 41.8% for Q6W and 55.9% for Q3W (HR 1.21, 95%CI 0.67-2.18). CONCLUSIONS: Q6W is an appropriate option for administering pembrolizumab, given the opportunity to reduce the health service resource burden.

Updates on Enhanced Recovery after Surgery protocols for plastic surgery of the breast and future directions.

Introduction: Perioperative pain control is an important component of any plastic surgery practice. Due to the incorporation of Enhanced Recovery after Surgery (ERAS) protocols, reported pain level, opioid consumption, and hospital length of stay numbers have decreased significantly. This article provides an up-to-date review of current ERAS protocols in use, reviews individual aspects of ERAS protocols, and discusses future directions for the continual improvement of ERAS protocols and control of postoperative pain. ERAS components: ERAS protocols have proven to be excellent methods of decreasing patient pain, opioid consumption, and postanesthesia care unit (PACU) and/or inpatient length of stay. ERAS protocols have three phases: preoperative education and pre-habilitation, intraoperative anesthetic blocks, and a postoperative multimodal analgesia regimen. Intraoperative blocks consist of local anesthetic field blocks and a variety of regional blocks, with lidocaine or lidocaine cocktails. Various studies throughout the surgical literature have demonstrated the efficacy of these aspects and their relevance to the overall goal of decreasing patient pain, both in plastic surgery and other surgical fields. In addition to the individual ERAS phases, ERAS protocols have shown promise in both the inpatient and outpatient sectors of plastic surgery of the breast. Conclusion: ERAS protocols have repeatedly been shown to provide improved patient pain control, decreased hospital or PACU length of stay, decreased opioid use, and cost savings. Although protocols have most commonly been utilized in inpatient plastic surgery procedures of the breast, emerging evidence points towards similar efficacy when used in outpatient procedures. Furthermore, this review demonstrates the efficacy of local anesthetic blocks in controlling patient pain.

Global Resilience in Plastic Surgery Study (GRIPS): Resilience is Associated with Lower Burnout Rates.

Burnout has earned notoriety in medicine. It affects medical students, residents and surgeons, causing a decrease in career satisfaction, quality of life, and increased risk of depression and suicide. The effect of resilience against burnout is yet unknown in plastic surgery trainees. Methods: A survey was sent via email to the members of plastic surgery societies (ICOPLAST) and the trainees from (ASPS) Resident Council from November 2021 through January 2022. The data included: demographics, training program characteristics, physician wellness resources, and single item Maslach-Burnout Inventory and Connor-Davidson Resilience Scale questionnaire. Results: One-hundred seventy-five plastic surgery trainees responded to the survey. Of these, 119 (68%) trainees from 24 countries completed the full survey. Most respondents 110 (92%) had heard of physician burnout, and almost half of respondents (45%) had burnout. The average Connor-Davidson Resilience Scale score varied significantly amongst trainees self-reporting burnout and those who did not (28.6 versus 31.3, P = 0.008). Multivariate logistic regression demonstrated that increased work hours per week were associated with an increased risk of burnout (OR = 1.03, P = 0.04). Higher resilience score (OR = 0.92; P = 0.04) and access to wellness programs (OR = 0.60, P = 0.0004) were associated with lower risk of burnout. Conclusions: Burnout is prevalent across plastic surgery trainees from diverse countries. Increased work hours were associated with burnout, whereas access to wellness programs and higher resilience scores were "protective." Our data suggest that efforts to build resilience may mitigate burnout in plastic surgery trainees.

Targeting synthetic lethal paralogs in cancer.

Synthetic lethal interactions, where mutation of one gene renders cells sensitive to inhibition of another gene, can be exploited for the development of targeted therapeutics in cancer. Pairs of duplicate genes (paralogs) often share common functionality and hence are a potentially rich source of synthetic lethal interactions. Because the majority of human genes have paralogs, exploiting such interactions could be a widely applicable approach for targeting gene loss in cancer. Moreover, existing small-molecule drugs may exploit synthetic lethal interactions by inhibiting multiple paralogs simultaneously. Consequently, the identification of synthetic lethal interactions between paralogs could be extremely informative for drug development. Here we review approaches to identify such interactions and discuss some of the challenges of exploiting them.

Idiopathic Interstitial Pneumonias: A Review of the Past and Emerging Therapies.

PurposeThis article is an in-depth review of the complex classification, diagnosis, and treatment of idiopathic interstitial pneumonias (IIP), as well as emergence of new treatment options. Summary: Idiopathic interstitial pneumonias consist of various subgroup classifications that require expert analysis of imaging and histology to accurately diagnose this broad group of patients. Timely and accurate assessment of these patients is key in developing an appropriate pharmacological plan. The pathophysiology of IIP is not well understood but has been linked to an immune response resulting in inflammation, fibrosis, or proliferation of lung tissue which reduces lung function. Lung transplantation is currently the only curative option for treatment, but many new antiproliferative and immunosuppressive agents are being used to effectively slow the progression of lung dysfunction. Conclusion: An often mixed radiological and histological pattern along with the invasive nature of biopsy for gold standard diagnosis create a challenge for the accurate identification of IIP. Further understanding of these idiopathic interstitial pneumonias will pave the way forward to the emergence of new treatment options and updates to standards of care.

A simulation-enhanced, spaced learning, interprofessional "code blue" curriculum improves ACLS algorithm adherence and trainee resuscitation skill confidence.

In-hospital cardiac arrest resuscitation training often happens in silos, with minimal interprofessional training. The aim of this study was to implement and evaluate a simulation-enhanced, interprofessional cardiac arrest curriculum in a university hospital. The curriculum ran monthly for 12 months, training interprofessional teams of internal medicine residents, nurses, respiratory therapists, and pharmacy residents. Teams participated in a 90-min high-fidelity simulation including "code blue" (30 min) followed by a 30-min debriefing and a repeat identical simulated "code blue" scenario. Teams were tested in an unannounced mock Code Blue the following month. Advanced Cardiac Life Support (ACLS) algorithm adherence was assessed using a standardized checklist. In-hospital cardiac arrest (IHCA) incidence and survival was tracked for 2 years prior, during, and 1 year after curriculum implementation. Team ACLS-algorithm adherence at baseline varied from 47% to 90% (mean of 71 ± 11%) and improved immediately following training (mean 88 ± 4%, range 80-93%, p = .011). This improvement persisted but decreased in magnitude over 1 month (mean 81 ± 7%, p = .013). Medical resident self-reported comfort levels with resuscitation skills varied widely at baseline, but improved for all skills post-curriculum. This simulation-enhanced, spaced practice, interprofessional curriculum resulted in a sustained improvement in team ACLS algorithm adherence.

Mutually exclusive genetic interactions and gene essentiality shape the genomic landscape of primary melanoma.

Melanoma is a heterogenous malignancy with an unpredictable clinical course. Most patients who present in the clinic are diagnosed with primary melanoma, yet large-scale sequencing efforts have focused primarily on metastatic disease. In this study we sequence-profiled 524 American Joint Committee on Cancer Stage I-III primary tumours. Our analysis of these data reveals recurrent driver mutations, mutually exclusive genetic interactions, where two genes were never or rarely co-mutated, and an absence of co-occurring genetic events. Further, we intersected copy number calls from our primary melanoma data with whole-genome CRISPR screening data to identify the transcription factor interferon regulatory factor 4 (IRF4) as a melanoma-associated dependency. © 2022 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Dendrimer nanotherapy for severe COVID-19 attenuates inflammation and neurological injury markers and improves outcomes in a phase2a clinical trial.

Hyperinflammation triggered by SARS-CoV-2 is a major cause of disease severity, with activated macrophages implicated in this response. OP-101, a hydroxyl-polyamidoamine dendrimer-N-acetylcysteine conjugate that specifically targets activated macrophages, improves outcomes in preclinical models of systemic inflammation and neuroinflammation. In this multicenter, randomized, double-blind, placebo-controlled, adaptive phase 2a trial, we evaluated safety and preliminary efficacy of OP-101 in patients with severe COVID-19. Twenty-four patients classified as having severe COVID-19 with a baseline World Health Organization seven-point ordinal scale of ≥5 were randomized to receive a single intravenous dose of placebo (n = 7 patients) or OP-101 at 2 (n = 6), 4 (n = 6), or 8 mg/kg (n = 5 patients). All study participants received standard of care, including corticosteroids. OP-101 at 4 mg/kg was better than placebo at decreasing inflammatory markers; OP-101 at 4 and 8 mg/kg was better than placebo at reducing neurological injury markers, (neurofilament light chain and glial fibrillary acidic protein). Risk for the composite outcome of mechanical ventilation or death at 30 and 60 days after treatment was 71% (95% CI: 29%, 96%) for placebo and 18% (95% CI: 4%, 43%; P = 0.021) for the pooled OP-101 treatment arms. At 60 days, 3 of 7 patients given placebo and 14 of 17 OP-101-treated patients were surviving. No drug-related adverse events were reported. These data show that OP-101 was well tolerated and may have potential to treat systemic inflammation and neuronal injury, reducing morbidity and mortality in hospitalized patients with severe COVID-19.

Analysis of Narcotic Use in Isolated Facial Fractures: Potential Targets for a Narcotic Reduction Protocol.

ABSTRACT: Anecdotal evidence suggests that patients with isolated traumatic facial fractures have high narcotic usage, yet there is a lack of literature delineating this relationship. This study aimed to characterize total amount and factors predictive of narcotic usage following isolated traumatic facial fracture. Study participants (n = 35) were predominantly male (91.4%), mean age 40.5, Caucasian (34.3%), suffered some form of assault (62.9%), and remained hospitalized for an average of 3.0 days. Average morphine milligram equivalent (MME) use in the inpatient setting was 967.6 for operative (n = 30) and 37.5 for nonoperative (n = 5) patients. Average total narcotic use across inpatient and outpatient settings was 1256.6 MME for operative and 105 MME for nonoperative patients. Operative intervention predicted a significant difference in total inpatient narcotic usage (P = 0.009). For patients who underwent surgical intervention, significant variations in narcotic usage were found based on mechanism of injury (24-hour postoperative, P = 0.030), but not injury severity or number of procedures. Specifically, individuals suffering highly traumatic fractures (eg, gunshot wound) demonstrated increased total postoperative narcotic usage of 1194.1 MME (P = 0.004). Interestingly, non-narcotic analgesic use including acetaminophen and lidocaine-epinephrine resulted in significantly lower narcotic usage in the postoperative setting. These findings suggest a role for narcotic-reducing enhanced recovery after surgery protocols in the setting of isolated facial trauma.

Improving the Standardized Letter of Recommendation in the Plastic Surgery Resident Selection Process.

OBJECTIVE: The American Council of Academic Plastic Surgeons (ACAPS) Plastic Surgery Recommendation Form is a standardized letter of recommendation (SLOR) used in the plastic surgery resident selection process since 2012. This study aims to evaluate this form and use a multistep survey to optimize this SLOR. DESIGN: A 16 question survey was sent via Survey Monkey to 510 ACAPS faculty. The results of this survey were followed up with a live-response survey at the ACAPS Spring Retreat. Consensus was used to modify and create a more optimal SLOR. SETTING: This study was performed by the Division of Plastic and Reconstructive Surgery at the University of California, San Diego. PARTICIPANTS: Survey respondents represented over five hundred plastic surgery faculty from a variety of subspecialties and academic programs nation-wide. RESULTS: The response rate to the online survey was 36%. On a scale of 1 (not useful) to 5 (very useful), letter readers and letter writers found the SLOR 3.88 and 3.90 respectively. Most respondents believed that the SLOR should be used as an adjunct to the narrative LOR. Forty-two faculties participated as respondents to the live audience questions, although over a 100 faculty were present for the discussion. Most participants agreed that independent program applicants should have a separate SLOR form, with at least 1 filled out by the Program Director of the residents' primary board. The majority (61%) of respondents supported the addition of 1-line characteristics to each applicant quality, and the change to a percentile format for assessment. CONCLUSIONS: Letters of recommendation are vital to the resident selection process, and thus it is incumbent upon fields of medicine to consciously work on improving how these letters are written. This study outlines a 2-step process by which a SLOR was evaluated and optimized for faculty in the field of plastic surgery.

Bronchoscopic Lung Volume Reduction with Valves and Coils. A Network Meta-analysis.

Background: Coils and endobronchial valves are the most widely used bronchoscopic lung volume reduction devices in patients with advanced emphysema. However, the choice of each specific device depends on emphysema characteristics (homogeneous vs. heterogeneous) and presence of lobar collateral ventilation (CV). These devices have not been compared in a head-to-head study design.Objectives: To conduct a network comparative meta-analysis studying the effect of valves in patients with heterogeneous emphysema without CV, and to also study the effects of valves and coils in patients with mixed homogeneous and heterogeneous emphysema.Data Sources and Data Extraction: PubMed and Web of Science were searched for potentially includable randomized active comparator trials from inception to January 20, 2020, and data were extracted in the working sheets of Comprehensive Meta-analysis.Synthesis: Network meta-analysis was conducted in R program using package "netmeta."Results: In patients with heterogeneous emphysema without CV, both Spiration and Zephyr valves showed significant increases in forced expiratory volume in 1 second (FEV1) (0.11 L [95% confidence interval (CI), 0.05 to 0.16] and 0.14 L [0.08 to 0.19], respectively) and in reducing St. Georges Respiratory Questionnaire (SGRQ) scores (-9.32 [-14.18 to -4.45] and -8.14 [-11.94 to -4.35], respectively) as compared with control, with no significant interintervention differences. Only Zephyr valves showed significant improvement (52.3 m [95% CI, 26.53 to 77.93]) in six-minute walk distance (6MWD). Both were ranked as equally efficacious in these patients. In the mixed homogeneous and heterogeneous emphysema group of patients, both Zephyr valves and coils showed significant increases in FEV1 and 6MWD and reduction in SGRQ, as compared with control. Although there were no significant interintervention differences, the magnitude of improvement in these parameters was highest with Zephyr valves (e.g., 6MWD increased by 56.74 m [23.66 to 89.81] vs. 30.31 m [4.00 to 56.63]) in coils), ranking them first. In both populations, these interventions showed a statistically significant association with procedure-related pneumothorax but not with chronic obstructive pulmonary disease exacerbation.Conclusions: In patients with heterogeneous emphysema without CV, both Zephyr and Spiration valves were equally efficacious in FEV1 and SGRQ improvement. However, in the mixed patients with homogeneous and heterogeneous emphysema, Zephyr valves show relative superiority over coils especially with respect to improvement in 6MWD.

Prevalence and Short-Term Clinical Outcome of Mobile Thrombi Detected on Transvenous Leads in Patients Undergoing Lead Extraction.

OBJECTIVES: This study sought to prospectively evaluate the prevalence, risk factors, and short-term major clinical outcomes of mobile thrombus detected on transvenous leads in patients undergoing lead extraction. BACKGROUND: The prevalence and clinical significance of thrombus on transvenous leads in patients undergoing lead extraction is not well characterized. METHODS: Consecutive patients undergoing transvenous lead extraction for noninfectious indications were enrolled. Preoperative transesophageal echocardiograms were performed prospectively for all patients to examine for mobile thrombus. Anticoagulation was not started for thrombus unless other indications were present. Clinical endpoints of mortality and cardiovascular morbidity (symptomatic pulmonary embolism, myocardial infarction, or cerebrovascular accident) were assessed at a minimum of 2-month follow-up. RESULTS: A total of 108 patients underwent lead extraction for noninfectious indications. Lead thrombi were detected in 20 (18.5%) patients and all were <2 cm. Clinical and lead characteristics were not associated with formation of lead thrombi, except for younger patient age. In patients with detected thrombi, there were no short-term deaths, symptomatic pulmonary embolisms, or myocardial infarctions, except 1 patient with a stroke 3 months after lead extraction (7% vs. 5%; p = 1.00). Median follow-up was 9 months. CONCLUSIONS: Mobile thrombi on transvenous leads are commonly found in patients referred for transvenous lead extraction and are rarely associated with acute major adverse outcomes. Careful extraction of leads with small incidentally detected thrombi can likely be performed without major acute clinical sequelae. Larger studies with longer follow-up are needed to further assess the long-term clinical significance of lead thrombi.

When does nutrition impact respiratory function?

Nutrition therapy is an essential aspect of patient care and an important determinant of outcomes in the ICU. Nutrition can impact respiratory function in a myriad of ways. Under- and overfeeding are two well-established ways by which nutrition impinges on respiratory function. Route of feeding, method of feeding, and carbohydrate composition of the diet are also other key factors regarding nutrition that influence outcomes in ICU patients. Recent studies are now elucidating the role of immune therapy in patients with acute respiratory distress syndrome. In the ICU, nutrition dogmas, such as the necessity of checking gastric residual volumes or utilizing full-calorie enteric feeds, as opposed to trophic feeds, are constantly being challenged by innovative clinical studies. Basic research brings the prospect of testing new approaches for ICU patients, such as the use of antioxidants to prevent diaphragm weakness in these patients. In this review article, we evaluate the recent observational and randomized control trials to critically appraise the evidence regarding nutrition in the ICU.

Measuring permeability with a whole cell-based biosensor as an alternate assay for angiogenesis: comparison with common in vitro assays.

Angiogenesis plays cardinal role in normal developmental processes as well as in numerous pathologies. Multiple cytokines are released and act simultaneously to activate endothelial cells in vivo. The present study investigated the relative ability of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), hepatocyte growth factor (HGF), tumor necrosis factor-alpha (TNF-alpha) in modulating cell monolayer permeability, migration, proliferation and tube formation individually and in combination. While the common methods for assaying angiogenesis were conducted for studying cell migration, proliferation and differentiation, endothelial cell monolayer permeability studies were carried out using a whole cell-based biosensor. The biosensor, consisting of a confluent monolayer of human umbilical vein endothelial cells (HUVECs) on a potassium ion-selective electrode, takes advantage of cell monolayer permeability dysfunction to detect the presence of small quantities of cytokines. When a confluent monolayer of cells was formed on the membrane surface, the response of the electrode toward the marker ion, potassium, was inhibited. The response obtained after exposing this sensor to different cytokines for 1 and 3h, can be attributed to the modulation of monolayer permeability by these cytokines. The present study demonstrated that at the concentrations experimented with, the relative change in permeability assay in the presence of cytokines compared to the control was much higher than that observed in other assays, thereby bolstering the potential of the biosensor to act as a quick screening tool for angiogenesis.