Lobar or Sublobar Resection for Peripheral Stage IA Non-Small-Cell Lung Cancer.

BACKGROUND: The increased detection of small-sized peripheral non-small-cell lung cancer (NSCLC) has renewed interest in sublobar resection in lieu of lobectomy. METHODS: We conducted a multicenter, noninferiority, phase 3 trial in which patients with NSCLC clinically staged as T1aN0 (tumor size, ≤2 cm) were randomly assigned to undergo sublobar resection or lobar resection after intraoperative confirmation of node-negative disease. The primary end point was disease-free survival, defined as the time between randomization and disease recurrence or death from any cause. Secondary end points were overall survival, locoregional and systemic recurrence, and pulmonary functions. RESULTS: From June 2007 through March 2017, a total of 697 patients were assigned to undergo sublobar resection (340 patients) or lobar resection (357 patients). After a median follow-up of 7 years, sublobar resection was noninferior to lobar resection for disease-free survival (hazard ratio for disease recurrence or death, 1.01; 90% confidence interval [CI], 0.83 to 1.24). In addition, overall survival after sublobar resection was similar to that after lobar resection (hazard ratio for death, 0.95; 95% CI, 0.72 to 1.26). The 5-year disease-free survival was 63.6% (95% CI, 57.9 to 68.8) after sublobar resection and 64.1% (95% CI, 58.5 to 69.0) after lobar resection. The 5-year overall survival was 80.3% (95% CI, 75.5 to 84.3) after sublobar resection and 78.9% (95% CI, 74.1 to 82.9) after lobar resection. No substantial difference was seen between the two groups in the incidence of locoregional or distant recurrence. At 6 months postoperatively, a between-group difference of 2 percentage points was measured in the median percentage of predicted forced expiratory volume in 1 second, favoring the sublobar-resection group. CONCLUSIONS: In patients with peripheral NSCLC with a tumor size of 2 cm or less and pathologically confirmed node-negative disease in the hilar and mediastinal lymph nodes, sublobar resection was not inferior to lobectomy with respect to disease-free survival. Overall survival was similar with the two procedures. (Funded by the National Cancer Institute and others; CALGB 140503 ClinicalTrials.gov number, NCT00499330.).

Crystal Structure, Steady-State, and Pre-Steady-State Kinetics of Acinetobacter baumannii ATP Phosphoribosyltransferase.

The first step of histidine biosynthesis in Acinetobacter baumannii, the condensation of ATP and 5-phospho-α-d-ribosyl-1-pyrophosphate to produce N1-(5-phospho-ß-d-ribosyl)-ATP (PRATP) and pyrophosphate, is catalyzed by the hetero-octameric enzyme ATP phosphoribosyltransferase, a promising target for antibiotic design. The catalytic subunit, HisGS, is allosterically activated upon binding of the regulatory subunit, HisZ, to form the hetero-octameric holoenzyme (ATPPRT), leading to a large increase in kcat. Here, we present the crystal structure of ATPPRT, along with kinetic investigations of the rate-limiting steps governing catalysis in the nonactivated (HisGS) and activated (ATPPRT) forms of the enzyme. A pH-rate profile showed that maximum catalysis is achieved above pH 8.0. Surprisingly, at 25 °C, kcat is higher when ADP replaces ATP as substrate for ATPPRT but not for HisGS. The HisGS-catalyzed reaction is limited by the chemical step, as suggested by the enhancement of kcat when Mg2+ was replaced by Mn2+, and by the lack of a pre-steady-state burst of product formation. Conversely, the ATPPRT-catalyzed reaction rate is determined by PRATP diffusion from the active site, as gleaned from a substantial solvent viscosity effect. A burst of product formation could be inferred from pre-steady-state kinetics, but the first turnover was too fast to be directly observed. Lowering the temperature to 5 °C allowed observation of the PRATP formation burst by ATPPRT. At this temperature, the single-turnover rate constant was significantly higher than kcat, providing additional evidence for a step after chemistry limiting catalysis by ATPPRT. This demonstrates allosteric activation by HisZ accelerates the chemical step.

The United States experience with diagnosing and treating esophageal cancer during the SARS-CoV-2 pandemic: A retrospective cohort study.

The downstream effects on healthcare delivery during the initial wave of the COVID-19 pandemic remain unclear. The purpose of this study was to determine how the healthcare environment surrounding the pandemic affected the oncologic care of patients diagnosed with esophageal cancer. This was a retrospective cohort study evaluating patients in the National Cancer Database (2019-2020). Patients with esophageal cancer diagnoses were divided into pre-pandemic (2019) and pandemic (2020) groups. Patient demographics, cancer-related variables, and treatment modalities were compared. Among 26,231 esophageal cancer patients, 14,024 patients (53.5%) were in the pre-pandemic cohort and 12,207 (46.5%) were in the pandemic cohort. After controlling for demographics, patients diagnosed during the pandemic were more likely to have poorly differentiated tumors (odds ratio [OR] 1.24, 95% confidence interval [CI] 1.08-1.42), pathologic T3 disease compared to T1 (OR 1.25, 95% CI 1.02-1.53), positive lymph nodes on pathology (OR 1.36, 95% CI 1.14-1.64), and to be pathologic stage IV (OR 1.51, 95% CI 1.29-1.76). After controlling for oncologic characteristics, patients diagnosed during the pandemic were more likely to require at least two courses of systemic therapy (OR 1.78, 95% CI 1.48-2.14) and to be offered palliative care (OR 1.13, 95% CI 1.04-1.22). While these patients were offered curative therapy at lower rates, this became non-significant after risk-adjustment (p = .15). The pandemic healthcare environment was associated with significantly increased risk-adjusted rates of patients presenting with advanced esophageal cancer. While this led to significant differences in treatment, most of these differences became non-significant after controlling for oncologic factors.

Anatomic Lung Resection Outcomes After Implementation of a Universal Thoracic ERAS Protocol Across a Diverse Health Care System.

OBJECTIVE: We sought to evaluate how implementing a thoracic enhanced recovery after surgery (ERAS) protocol impacted surgical outcomes after elective anatomic lung resection. BACKGROUND: The effect of implementing the ERAS Society/European Society of Thoracic Surgery thoracic ERAS protocol on postoperative outcomes throughout an entire health care system has not yet been reported. METHODS: This was a prospective cohort study within one health care system (January 2019-March, 2023). A thoracic ERAS protocol was implemented on May 1, 2021 for elective anatomic lung resections, and postoperative outcomes were tracked using the electronic health record and Vizient data. The primary outcome was overall morbidity; secondary outcomes included individual complications, length of stay, opioid use, chest tube duration, and total cost. Patients were grouped into pre-ERAS and post-ERAS cohorts. Bivariable comparisons were performed using independent t -test, χ 2 , or Fisher exact tests, and multivariable logistic regression was performed to control for confounders. RESULTS: There were 1007 patients in the cohort; 450 (44.7%) were in the post-ERAS group. Mean age was 66.2 years; most patients were female (65.1%), white (83.8%), had a body mass index between 18.5 and 29.9 (69.7%), and were ASA class 3 (80.6%). Patients in the postimplementation group had lower risk-adjusted rates of any morbidity, respiratory complication, pneumonia, surgical site infection, arrhythmias, infections, opioid usage, ICU use, and shorter postoperative length of stay (all P <0.05). CONCLUSIONS: Postoperative outcomes were improved after the implementation of an evidence-based thoracic ERAS protocol throughout the health care system. This study validates the ERAS Society/European Society of Thoracic Surgery guidelines and demonstrates that simultaneous multihospital implementation can be feasible and effective.

The Effect of Laparoscopic Gastric Ischemic Preconditioning Prior to Esophagectomy on Anastomotic Stricture Rate and Comparison with Esophagectomy-Alone Controls.

BACKGROUND: Benign anastomotic stricture is a recognized complication following esophagectomy. Laparoscopic gastric ischemic preconditioning (LGIP) prior to esophagectomy has been associated with decreased anastomotic leak rates; however, its effect on stricture and the need for subsequent endoscopic intervention is not well studied. METHODS: This was a case-control study at an academic medical center using consecutive patients undergoing oncologic esophagectomies (July 2012-July 2022). Our institution initiated an LGIP protocol on 1 January 2021. The primary outcome was the occurrence of stricture within 1 year of esophagectomy, while secondary outcomes were stricture severity and frequency of interventions within the 6 months following stricture. Bivariable comparisons were performed using Chi-square, Fisher's exact, or Mann-Whitney U tests. Multivariable regression controlling for confounders was performed to generate risk-adjust odds ratios and to identify the independent effect of LGIP. RESULTS: Of 253 esophagectomies, 42 (16.6%) underwent LGIP prior to esophagectomy. There were 45 (17.7%) anastomotic strictures requiring endoscopic intervention, including three patients who underwent LGIP and 42 who did not. Median time to stricture was 144 days. Those who underwent LGIP were significantly less likely to develop anastomotic stricture (7.1% vs. 19.9%; p = 0.048). After controlling for confounders, this difference was no longer significant (odds ratio 0.46, 95% confidence interval 0.14-1.82; p = 0.29). Of those who developed stricture, there was a trend toward less severe strictures and decreased need for endoscopic dilation in the LGIP group (all p < 0.20). CONCLUSION: LGIP may reduce the rate and severity of symptomatic anastomotic stricture following esophagectomy. A multi-institutional trial evaluating the effect of LGIP on stricture and other anastomotic complications is warranted.

Fisetin Attenuates Cellular Senescence Accumulation During Culture Expansion of Human Adipose-Derived Stem Cells.

Mesenchymal stem cells (MSCs) have long been viewed as a promising therapeutic for musculoskeletal repair. However, regulatory concerns including tumorgenicity, inconsistencies in preparation techniques, donor-to-donor variability, and the accumulation of senescence during culture expansion have hindered the clinical application of MSCs. Senescence is a driving mechanism for MSC dysfunction with advancing age. Often characterized by increased reactive oxygen species, senescence-associated heterochromatin foci, inflammatory cytokine secretion, and reduced proliferative capacity, senescence directly inhibits MSCs efficacy as a therapeutic for musculoskeletal regeneration. Furthermore, autologous delivery of senescent MSCs can further induce disease and aging progression through the secretion of the senescence-associated secretory phenotype (SASP) and mitigate the regenerative potential of MSCs. To alleviate these issues, the use of senolytic agents to selectively clear senescent cell populations has become popular. However, their benefits to attenuating senescence accumulation in human MSCs during the culture expansion process have not yet been elucidated. To address this, we analyzed markers of senescence during the expansion of human primary adipose-derived stem cells (ADSCs), a population of fat-resident MSCs commonly used in regenerative medicine applications. Next, we used the senolytic agent fisetin to determine if we can reduce these markers of senescence within our culture-expanded ADSC populations. Our results indicate that ADSCs acquire common markers of cellular senescence including increased reactive oxygen species, senescence-associated ß-galactosidase, and senescence-associated heterochromatin foci. Furthermore, we found that the senolytic agent fisetin works in a dose-dependent manner and selectively attenuates these markers of senescence while maintaining the differentiation potential of the expanded ADSCs.

Competency-Based Time-Variable Anesthesiology Residency Training: Identification of Problems and Solutions.

BACKGROUND: Global medical education is gradually moving toward more comprehensive implementations of a competency-based education (CBE) model. Elimination of standard time-based training and adoption of time-variable training (competency-based time-variable training [CB-TVT]) is one of the final stages of implementation of CBE. While CB-TVT has been implemented in some programs outside the United States, residency programs in the United States are still exploring this approach to training. The Accreditation Council for Graduate Medical Education (ACGME) and the American Board of Medical Specialties (ABMS) are encouraging member boards and residency review committees to consider innovative ways programs could implement CB-TVT. The goals of this study were to (1) identify potential problems with the implementation of CB-TVT in anesthesiology residency training, (2) rank the importance of the problems and the perceived difficulty of solving them, and (3) develop proposed solutions to the identified problems. METHODS: Study participants were recruited from key stakeholder groups in anesthesiology education, including current or former program directors, department chairs, residents, fellows, American Board of Anesthesiology (ABA) board members, ACGME residency review committee members or ACGME leaders, designated institutional officials, residency program coordinators, clinical operations directors, and leaders of large anesthesiology community practice groups. This study was conducted in 2 phases. In phase 1, survey questionnaires were iteratively distributed to participants to identify problems with the implementation of CB-TVT. Participants were also asked to rank the perceived importance and difficulty of each problem and to identify relevant stakeholder groups that would be responsible for solving each problem. In phase 2, surveys focused on identifying potential solutions for problems identified in phase 1. RESULTS: A total of 36 stakeholders identified 39 potential problems, grouped into 7 major categories, with the implementation of CB-TVT in anesthesiology residency training. Of the 39 problems, 19 (48.7%) were marked as important or very important on a 5-point scale and 12 of 19 (63.2%) of the important problems were marked as difficult or very difficult to solve on a 5-point scale. Stakeholders proposed 165 total solutions to the identified problems. CONCLUSIONS: CB-TVT is a promising educational model for anesthesiology residency, which potentially results in learner flexibility, individualization of curricula, and utilization of competencies to determine learner advancement. Because of the potential problems with the implementation of CB-TVT, it is important for future pilot implementations of CB-TVT to document realized problems, efficacy of solutions, and effects on educational outcomes to justify the burden of implementing CB-TVT.

Development and Pilot Testing of a Programmatic System for Competency Assessment in US Anesthesiology Residency Training.

BACKGROUND: In 2018, a set of entrustable professional activities (EPAs) and procedural skills assessments were developed for anesthesiology training, but they did not assess all the Accreditation Council for Graduate Medical Education (ACGME) milestones. The aims of this study were to (1) remap the 2018 EPA and procedural skills assessments to the revised ACGME Anesthesiology Milestones 2.0, (2) develop new assessments that combined with the original assessments to create a system of assessment that addresses all level 1 to 4 milestones, and (3) provide evidence for the validity of the assessments. METHODS: Using a modified Delphi process, a panel of anesthesiology education experts remapped the original assessments developed in 2018 to the Anesthesiology Milestones 2.0 and developed new assessments to create a system that assessed all level 1 through 4 milestones. Following a 24-month pilot at 7 institutions, the number of EPA and procedural skill assessments and mean scores were computed at the end of the academic year. Milestone achievement and subcompetency data for assessments from a single institution were compared to scores assigned by the institution's clinical competency committee (CCC). RESULTS: New assessment development, 2 months of testing and feedback, and revisions resulted in 5 new EPAs, 11 nontechnical skills assessments (NTSAs), and 6 objective structured clinical examinations (OSCEs). Combined with the original 20 EPAs and procedural skills assessments, the new system of assessment addresses 99% of level 1 to 4 Anesthesiology Milestones 2.0. During the 24-month pilot, aggregate mean EPA and procedural skill scores significantly increased with year in training. System subcompetency scores correlated significantly with 15 of 23 (65.2%) corresponding CCC scores at a single institution, but 8 correlations (36.4%) were <30.0, illustrating poor correlation. CONCLUSIONS: A panel of experts developed a set of EPAs, procedural skill assessment, NTSAs, and OSCEs to form a programmatic system of assessment for anesthesiology residency training in the United States. The method used to develop and pilot test the assessments, the progression of assessment scores with time in training, and the correlation of assessment scores with CCC scoring of milestone achievement provide evidence for the validity of the assessments.

Major pneumothorax during pediatric cardiac MRI procedure under general anesthesia: step-by-step analysis and importance of a well-known environment and material.

BACKGROUND: To perform step-by-step analysis of the different factors (material, anesthesia technique, human, and location) that led to major pneumothorax during an infrequent pediatric cardiac MRI and to prevent its occurrence in the future. Anesthesia equipment used in a remote location is often different than those in operating rooms. For magnetic resonance imaging (MRI), ventilation devices and monitors must be compatible with the magnetic fields. During cardiac MRI numerous apneas are required and, visual contact with the patient is limited for clinical evaluation. Anesthesia-related barotrauma and pneumothorax are rare in children and the first symptoms can be masked. CASE PRESENTATION: A 3-year-old boy with atrial septal defect (ASD) and suspicious partial anomalous pulmonary venous return was anesthetized and intubated to perform a follow up with MRI. Sevoflurane maintenance and ventilation were performed using a circular CO2 absorber device, co-axial circuit, and 500 mL pediatric silicone balloon. Apneas were facilitated by Alfentanyl boluses and hyperventilation. A few moderated desaturations occurred during the imaging sequences without hemodynamic changes. At the end of the MRI, facial subcutaneous emphysema was observed by swollen eyelids and crackling snow neck palpation. A complete left pneumothorax was diagnosed by auscultation, sonography examination, and chest radiograph. Pneumo-mediastinum, -pericardium and -peritoneum were present. A chest drain was placed, and the child was extubated and transferred to the pediatric intensive care unit (PICU). Despite the anesthesiologist's belief that PEEP was minimal, critical analysis revealed that PEEP was maintained at a high level throughout anesthesia. After the initial barotrauma, repeated exposure to high pressure led to the diffusion of air from the pleura to subcutaneous tissues and mediastinal and peritoneal cavities. Equipment check revealed a functional circular circuit; however, the plastic adjustable pressure-limiting valve (APL) closed within the last 30° rotation. The balloon was found to be more rigid and demonstrated significantly reduced compliance. CONCLUSIONS: Anesthetists require proficiency is using equipment in non-OR locations and this equipment must be properly maintained and checked for malfunctions. Controlling the human factor risks by implementing checklists, formations, and alarms allows us to reduce errors. The number of pediatric anesthesia performed routinely appeared to be essential for limiting risks and reporting our mistakes will be a benefit for all who care about patients.

Assessing the quality and value of metabolic chart data for capturing core outcomes for pediatric medium-chain acyl-CoA dehydrogenase (MCAD) deficiency.

BACKGROUND: Generating rigorous evidence to inform care for rare diseases requires reliable, sustainable, and longitudinal measurement of priority outcomes. Having developed a core outcome set for pediatric medium-chain acyl-CoA dehydrogenase (MCAD) deficiency, we aimed to assess the feasibility of prospective measurement of these core outcomes during routine metabolic clinic visits. METHODS: We used existing cohort data abstracted from charts of 124 children diagnosed with MCAD deficiency who participated in a Canadian study which collected data from birth to a maximum of 11 years of age to investigate the frequency of clinic visits and quality of metabolic chart data for selected outcomes. We recorded all opportunities to collect outcomes from the medical chart as a function of visit rate to the metabolic clinic, by treatment centre and by child age. We applied a data quality framework to evaluate data based on completeness, conformance, and plausibility for four core MCAD outcomes: emergency department use, fasting time, metabolic decompensation, and death. RESULTS: The frequency of metabolic clinic visits decreased with increasing age, from a rate of 2.8 visits per child per year (95% confidence interval, 2.3-3.3) among infants 2 to 6 months, to 1.0 visit per child per year (95% confidence interval, 0.9-1.2) among those ≥ 5 years of age. Rates of emergency department visits followed anticipated trends by child age. Supplemental findings suggested that some emergency visits occur outside of the metabolic care treatment centre but are not captured. Recommended fasting times were updated relatively infrequently in patients' metabolic charts. Episodes of metabolic decompensation were identifiable but required an operational definition based on acute manifestations most commonly recorded in the metabolic chart. Deaths occurred rarely in these patients and quality of mortality data was not evaluated. CONCLUSIONS: Opportunities to record core outcomes at the metabolic clinic occur at least annually for children with MCAD deficiency. Methods to comprehensively capture emergency care received at outside institutions are needed. To reduce substantial heterogeneous recording of core outcome across treatment centres, improved documentation standards are required for recording of recommended fasting times and a consensus definition for metabolic decompensations needs to be developed and implemented.

Preoperative Heart Failure Treatment Prevents Postoperative Cardiac Complications in Patients With Lower Risk: A Retrospective Cohort Study.

OBJECTIVE: The objective of this study was to identify undertreated subgroups of patients with heart failure who would benefit from better perioperative optimization. SUMMARY OF BACKGROUND DATA: Patients with heart failure have increased risks of postoperative cardiac complications after noncardiac surgery. METHODS: In this analysis of hospital registry data of 130,677 patients undergoing noncardiac surgery, the exposure was preoperative history of heart failure. The outcome, cardiac complications, was defined as a composite of myocardial infarction, cardiac arrest, acute heart failure, and mortality within 30 postoperative days. RESULTS: History of heart failure (n = 10,256; 7.9%) was associated with increased risk of cardiac complications [8.1% vs 1.1%; adjusted odds ratio, 2.28 (95% CI, 2.02-2.56); P < 0.001). Patients with heart failure and who carried a lower risk profile had increased risks of postoperative cardiac complications secondary to heart failure [adjusted absolute risk difference, 1.7% (95% CI, 1.4%-2.0%, lower risk); P < 0.001 vs 0.5% (95% CI, -0.6% to 1.6%, higher risk); P = 0.38]. Patients with heart failure and lower risk received a lower level of health care utilization preoperatively, and less frequently received anti-heart failure medications (59% vs 72% and 61% vs 82%; both P < 0.001). These preventive therapies significantly decreased the risk of cardiac complications in patients with heart failure. CONCLUSIONS: In patients with heart failure who have a lower preoperative risk profile, clinicians often make insufficient attempts to optimize their clinical condition preoperatively. Preoperative preventive treatment reduces the risk of postoperative cardiac complications in these lower-risk patients with heart failure.

Prospective Evaluation of a Universally Applied Laparoscopic Gastric Ischemic Preconditioning Protocol Prior to Esophagectomy with Comparison with Historical Controls.

BACKGROUND: Anastomotic leak after esophagectomy is associated with significant morbidity and mortality. Our institution began performing laparoscopic gastric ischemic preconditioning (LGIP) with ligation of the left gastric and short gastric vessels prior to esophagectomy in all patients presenting with resectable esophageal cancer. We hypothesized that LGIP may decrease the incidence and severity of anastomotic leak. METHODS: Patients were prospectively evaluated following the universal application of LGIP prior to esophagectomy protocol in January 2021 until August 2022. Outcomes were compared with patients who underwent esophagectomy without LGIP from a prospectively maintained database from 2010 to 2020. RESULTS: We compared 42 patients who underwent LGIP followed by esophagectomy with 222 who underwent esophagectomy without LGIP. Age, sex, comorbidities, and clinical stage were similar between groups. Outpatient LGIP was generally well tolerated, with one patient experiencing prolonged gastroparesis. Median time from LGIP to esophagectomy was 31 days. Mean operative time and blood loss were not significantly different between groups. Patients who underwent LGIP were significantly less likely to develop an anastomotic leak following esophagectomy (7.1% vs. 20.7%, p = 0.038). This finding persisted on multivariate analysis [odds ratio (OR) 0.17, 95% confidence interval (CI) 0.03-0.42, p = 0.029]. The occurrence of any post-esophagectomy complication was similar between groups (40.5% vs. 46.0%, p = 0.514), but patients who underwent LGIP had shorter length of stay [10 (9-11) vs. 12 (9-15), p = 0.020]. CONCLUSIONS: LGIP prior to esophagectomy is associated with a decreased risk of anastomotic leak and length of hospital stay. Further, multi-institutional studies are warranted to confirm these findings.

Evaluation of Technical Performance of Ultrasound-Guided Procedures through Hand Motion Analysis: An Exploration of Motion Metrics.

PURPOSE: To evaluate the ability of hand motion analysis using conventional and new motion metrics to differentiate between operators of varying levels of experience for central venous access (CVA) and liver biopsy (LB). MATERIALS AND METHODS: In the CVA task, 7 interventional radiologists (experts), 10 senior trainees, and 5 junior trainees performed ultrasound-guided CVA on a standardized manikin; 5 trainees were retested after 1 year. In the LB task, 4 radiologists (experts) and 7 trainees biopsied a lesion on a manikin. Conventional motion metrics (path length and task time), a refined metric (translational movements), and new metrics (rotational sum and rotational movements) were calculated. RESULTS: In the CVA task, experts outperformed trainees on all metrics (P < .02). Senior trainees required fewer rotational movements (P = .02), translational movements (P = .045), and time (P = .001) than junior trainees. Similarly, on 1-year follow-up, trainees had fewer translational (P = .02) and rotational (P = .003) movements with less task time (P = .003). The path length and rotational sum were not different between junior and senior trainees or for trainees on follow-up. Rotational and translational movements had greater area under the curve values (0.91 and 0.86, respectively) than the rotational sum (0.73) and path length (0.61). In the LB task, experts performed the task with a shorter path length (P = .04), fewer translational (P = .04) and rotational (P = .02) movements, and less time (P < .001) relative to the trainees. CONCLUSIONS: Hand motion analysis using translational and rotational movements was better at differentiating levels of experience and improvement with training than the conventional metric of path length.

Distractions in the operating room: a survey of the healthcare team.

BACKGROUND: Distractions during surgical procedures are associated with team inefficiency and medical error. Little is published about the healthcare provider's perception of distraction and its adverse impact in the operating room. We aim to explore the perception of the operating room team on multiple distractions during surgical procedures. METHODS: A 26-question survey was administered to surgeons, anesthesia team members, nurses, and scrub technicians at our institution. Respondents were asked to identify and rank multiple distractions and indicate how each distraction might affect the flow of surgery. RESULTS: There was 160 responders for a response rate of 19.18% (160/834), of which 71 (44.1%) male and 82 (50.9%) female, 48 (29.8%) surgeons, 59 (36.6%) anesthesiologists, Certified Registered Nurse Anesthetists (CRNA), and 53 (32.9%) OR nurses and scrub technicians. Responders were classified into a junior group (< 10 years of experience) and a senior group (≥ 10 years). Auditory distraction followed by equipment were the most distracting factors in the operating room. All potential auditory distractions in this survey were associated with higher percentage of certain level of negative impact on the flow of surgery except for music. The top 5 distractors belonged to equipment and environment categories. Phone calls/ pagers/ beepers and case relevant communications were consistently among the top 5 most common distractors. Case relevant communications, music, teaching, and consultation were the top 4 most perceived positive impact on the flow of surgery. Distractors with higher levels of "bothersome" rating appeared to associate with a higher level of perceived negative impact on the flow of surgery. Vision was the least distracting factor and appeared to cause minimal positive impact on the flow of surgery. CONCLUSIONS: To our knowledge, this is the first survey studying perception of surgery, anesthesia, and OR staff on various distractions in the operating room. Fewer unnecessary distractions might improve the flow of surgery, improve OR teamwork, and potentially improve patient outcomes.

Virtual Reality: The Future of Invasive Procedure Training?

Invasive procedures are associated with adverse events that are both hazardous to patients and expensive to treat. A trainee is expected to perform complex sterile invasive procedures in a dynamic environment under time pressure while maintaining patient safety at the highest standard of care. For mastery in performing an invasive procedure, the automatism of the technical aspects is required, as well as the ability to adapt to patient conditions, anatomic variability, and environmental stressors. Virtual reality (VR) simulation training is an immersive technology with immense potential for medical training, potentially enhancing clinical proficiency and improving patient safety. Virtual reality can project near-realistic environments onto a head-mounted display, allowing users to simulate and interact with various scenarios. Virtual reality has been used extensively for task training in various healthcare-related disciplines and other fields, such as the military. These scenarios often incorporate haptic feedback for the simulation of physical touch and audio and visual stimuli. In this manuscript, the authors have presented a historical review, the current status, and the potential application of VR simulation training for invasive procedures. They specifically explore a VR training module for central venous access as a prototype for invasive procedure training to describe the advantages and limitations of this evolving technology.

In vitro assessment of antimicrobial potential of low molecular weight chitosan and its ability to mechanically reinforce and control endogenous proteolytic activity of dentine.

AIMS: Chitosan-based biomaterials exhibit several properties of biological interest for endodontic treatment. Herein, a low molecular weight chitosan (CH) solution was tested for its antimicrobial activity against Enterococcus faecalis (E. faecalis) and effects on dentine structure. METHODOLOGY: The root canal of 27 extracted uniradicular teeth were biomechanically prepared, inoculated with a suspension of E. faecalis and randomly assigned to be irrigated with either 5.25% sodium hypochlorite (NaClO), 0.2% CH or sterile ultrapure water (W). Bacteriologic samples were collected from root canals and quantified for of E. faecalis colony-forming units (CFUs). The effectiveness of CH over E. faecalis biofilms was further measured using the MBEC Assay®. Additionally, dentine beams and dentine powder were obtained, respectively, from crowns and roots of 20 extracted third molars. Dentine samples were treated or not with 17% EDTA and immersed in either CH or W for 1 min. The effects of CH on dentine structure were evaluated by assessment of the modulus of elasticity, endogenous proteolytic activity and biochemical modifications. RESULTS: The number of E. faecalis CFUs was significantly lower for samples irrigated with CH and NaClO. No significant differences were found between CH and NaClO treatments. Higher modulus of elasticity and lower proteolytic activity were reported for dentine CH-treated specimens. Chemical interaction between CH and dentine was observed for samples treated or not with EDTA. CONCLUSIONS: Present findings suggest that CH could be used as an irrigant during root canal treatment with the triple benefit of reducing bacterial activity, mechanically reinforcing dentine and inhibiting dentine proteolytic activity.

Measuring deliberate reflection in residents: validation and psychometric properties of a measurement tool.

PURPOSE: Reflective capacity is "the ability to understand critical analysis of knowledge and experience to achieve deeper meaning." In medicine, there is little provision for post-graduate medical education to teach deliberate reflection. The feasibility, scoring characteristics, reliability, validation, and adaptability of a modified previously validated instrument was examined for its usefulness assessing reflective capacity in residents as a step toward developing interventions for improvement. METHODS: Third-year residents and fellows from four anesthesia training programs were administered a slightly modified version of the Reflection Evaluation for Learners' Enhanced Competencies Tool (REFLECT) in a prospective, observational study at the end of the 2019 academic year. Six written vignettes of imperfect anesthesia situations were created. Subjects recorded their perspectives on two randomly assigned vignettes. Responses were scored using a 5-element rubric; average scores were analyzed for psychometric properties. An independent self-report assessment method, the Cognitive Behavior Survey: Residency Level (rCBS) was used to examine construct validity. Internal consistency (ICR, Cronbach's alpha) and interrater reliability (weighted kappa) were examined. Pearson correlations were used between the two measures of reflective capacity. RESULTS: 46/136 invited subjects completed 2/6 randomly assigned vignettes. Interrater agreement was high (k = 0.85). The overall average REFLECT score was 1.8 (1-4 scale) with good distribution across the range of scores. ICR for both the REFLECT score (mean 1.8, sd 0.5; α = 0.92) and the reflection scale of the rCBS (mean 4.5, sd 1.1; α = 0.94) were excellent. There was a significant correlation between REFLECT score and the rCBS reflection scale (r = .44, p < 0.01). CONCLUSIONS: This study demonstrates feasibility, reliability, and sufficiently robust psychometric properties of a modified REFLECT rubric to assess graduate medical trainees' reflective capacity and established construct/convergent validity to an independent measure. The instrument has the potential to assess the effectiveness of interventions intended to improve reflective capacity.

Plant Cell-Engineered Gold Nanoparticles Conjugated to Quercetin Inhibit SARS-CoV-2 and HSV-1 Entry.

Recent studies have revealed considerable promise in the antiviral properties of metal nanomaterials, specifically when biologically prepared. This study demonstrates for the first time the antiviral roles of the plant cell-engineered gold nanoparticles (pAuNPs) alone and when conjugated with quercetin (pAuNPsQ). We show here that the quercetin conjugated nanoparticles (pAuNPsQ) preferentially inhibit the cell entry of two medically important viruses-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and herpes simplex virus type-1 (HSV-1) using different mechanisms. Interestingly, in the case of SARS-CoV-2, the pre-treatment of target cells with pAuNPsQ inhibited the viral entry, but the pre-treatment of the virus with pAuNPsQ did not affect viral entry into the host cell. In contrast, pAuNPsQ demonstrated effective blocking capabilities against HSV-1 entry, either during the pre-treatment of target cells or by inducing virus neutralization. In addition, pAuNPsQ also significantly affected HSV-1 replication, evidenced by the plaque-counting assay. In this study, we also tested the chemically synthesized gold nanoparticles (cAuNPs) of identical size and shape and observed comparable effects. The versatility of plant cell-based nanomaterial fabrication and its modification with bioactive compounds opens a new frontier in therapeutics, specifically in designing novel antiviral formulations.

Practical application of a Bayesian network approach to poultry epigenetics and stress.

BACKGROUND: Relationships among genetic or epigenetic features can be explored by learning probabilistic networks and unravelling the dependencies among a set of given genetic/epigenetic features. Bayesian networks (BNs) consist of nodes that represent the variables and arcs that represent the probabilistic relationships between the variables. However, practical guidance on how to make choices among the wide array of possibilities in Bayesian network analysis is limited. Our study aimed to apply a BN approach, while clearly laying out our analysis choices as an example for future researchers, in order to provide further insights into the relationships among epigenetic features and a stressful condition in chickens (Gallus gallus). RESULTS: Chickens raised under control conditions (n = 22) and chickens exposed to a social isolation protocol (n = 24) were used to identify differentially methylated regions (DMRs). A total of 60 DMRs were selected by a threshold, after bioinformatic pre-processing and analysis. The treatment was included as a binary variable (control = 0; stress = 1). Thereafter, a BN approach was applied: initially, a pre-filtering test was used for identifying pairs of features that must not be included in the process of learning the structure of the network; then, the average probability values for each arc of being part of the network were calculated; and finally, the arcs that were part of the consensus network were selected. The structure of the BN consisted of 47 out of 61 features (60 DMRs and the stressful condition), displaying 43 functional relationships. The stress condition was connected to two DMRs, one of them playing a role in tight and adhesive intracellular junctions in organs such as ovary, intestine, and brain. CONCLUSIONS: We clearly explain our steps in making each analysis choice, from discrete BN models to final generation of a consensus network from multiple model averaging searches. The epigenetic BN unravelled functional relationships among the DMRs, as well as epigenetic features in close association with the stressful condition the chickens were exposed to. The DMRs interacting with the stress condition could be further explored in future studies as possible biomarkers of stress in poultry species.

Efficacy and safety of empagliflozin in glycogen storage disease type Ib: Data from an international questionnaire.

PURPOSE: This paper aims to report collective information on safety and efficacy of empagliflozin drug repurposing in individuals with glycogen storage disease type Ib (GSD Ib). METHODS: This is an international retrospective questionnaire study on the safety and efficacy of empagliflozin use for management of neutropenia/neutrophil dysfunction in patients with GSD Ib, conducted among the respective health care providers from 24 countries across the globe. RESULTS: Clinical data from 112 individuals with GSD Ib were evaluated, representing a total of 94 treatment years. The median age at start of empagliflozin treatment was 10.5 years (range = 0-38 years). Empagliflozin showed positive effects on all neutrophil dysfunction-related symptoms, including oral and urogenital mucosal lesions, recurrent infections, skin abscesses, inflammatory bowel disease, and anemia. Before initiating empagliflozin, most patients with GSD Ib were on G-CSF (94/112; 84%). At the time of the survey, 49 of 89 (55%) patients previously treated with G-CSF had completely stopped G-CSF, and another 15 (17%) were able to reduce the dose. The most common adverse event during empagliflozin treatment was hypoglycemia, occurring in 18% of individuals. CONCLUSION: Empagliflozin has a favorable effect on neutropenia/neutrophil dysfunction-related symptoms and safety profile in individuals with GSD Ib.