Clinical validation of C12FDG as a marker associated with senescence and osteoarthritic phenotypes.

Chronic conditions associated with aging have proven difficult to prevent or treat. Senescence is a cell fate defined by loss of proliferative capacity and the development of a pro-inflammatory senescence-associated secretory phenotype comprised of cytokines/chemokines, proteases, and other factors that promotes age-related diseases. Specifically, an increase in senescent peripheral blood mononuclear cells (PBMCs), including T cells, is associated with conditions like frailty, rheumatoid arthritis, and bone loss. However, it is unknown if the percentage of senescent PBMCs associated with age-associated orthopedic decline could be used for potential diagnostic or prognostic use in orthopedics. Here, we report senescent cell detection using the fluorescent compound C12FDG to quantify PBMCs senescence across a large cohort of healthy and osteoarthritic patients. There is an increase in the percent of circulating C12FDG+ PBMCs that is commensurate with increases in age and senescence-related serum biomarkers. Interestingly, C12FDG+ PBMCs and T cells also were found to be elevated in patients with mild to moderate osteoarthritis, a progressive joint disease that is strongly associated with inflammation. The percent of C12FDG+ PBMCs and age-related serum biomarkers were decreased in a small subgroup of study participants taking the senolytic drug fisetin. These results demonstrate quantifiable measurements in a large group of participants that could create a composite score of healthy aging sensitive enough to detect changes following senolytic therapy and may predict age-related orthopedic decline. Detection of peripheral senescence in PBMCs and subsets using C12FDG may be clinically useful for quantifying cellular senescence and determining how and if it plays a pathological role in osteoarthritic progression.

Use of marine occurrent extracts to enhance the stability of dentin extracellular matrix.

Chitosan (CS) and phloroglucinol (PhG), two extracts abundantly found in marine life, were investigated for their ability to biomodify demineralized dentin by enhancing collagen crosslinks and improving dentin extracellular matrix (ECM) mechanical and biochemical stability. Dentin obtained from non-carious extracted human molars were demineralized with phosphoric acid. Baseline Fourier-transform infrared (FTIR) spectra, apparent flexural elastic modulus (AE) and dry mass (DM) of each specimen were independently acquired. Specimens were randomly incubated for 5 min into either ultrapure water (no-treatment), 1% glutaraldehyde (GA), 1% CS or 1% PhG. Water and GA were used, respectively, as a negative and positive control for collagen crosslinks. Specimens' post-treatment FTIR spectra, AE, and DM were obtained and compared with correspondent baseline measurements. Additionally, the host-derived proteolytic activity of dentin ECM was assessed using hydroxyproline assay (HYP) and spectrofluorometric analysis of a fluorescent-quenched substrate specific for matrix metalloproteinases (MMPs). Finally, the bond strength of an etch-and-rinse adhesive was evaluated after application of marine compounds as non-rinsing dentin primers. Dentin specimens FTIR spectral profile changed remarkably, and their AE increased significantly after treatment with marine compounds. DM variation, HYP assay and fluorogenic substrate analysis concurrently indicated the biodegradation of CS- and PhG-treated specimens was significantly lesser in comparison with untreated specimens. CS and PhG treatments enhanced biomechanical/biochemical stability of demineralized dentin. These novel results show that PhG is a primer with the capacity to biomodify demineralized dentin, hence rendering it less susceptible to biodegradation by host-proteases.

Allosteric activation unveils protein-mass modulation of ATP phosphoribosyltransferase product release.

Heavy-isotope substitution into enzymes slows down bond vibrations and may alter transition-state barrier crossing probability if this is coupled to fast protein motions. ATP phosphoribosyltransferase from Acinetobacter baumannii is a multi-protein complex where the regulatory protein HisZ allosterically enhances catalysis by the catalytic protein HisGS. This is accompanied by a shift in rate-limiting step from chemistry to product release. Here we report that isotope-labelling of HisGS has no effect on the nonactivated reaction, which involves negative activation heat capacity, while HisZ-activated HisGS catalytic rate decreases in a strictly mass-dependent fashion across five different HisGS masses, at low temperatures. Surprisingly, the effect is not linked to the chemical step, but to fast motions governing product release in the activated enzyme. Disruption of a specific enzyme-product interaction abolishes the isotope effects. Results highlight how altered protein mass perturbs allosterically modulated thermal motions relevant to the catalytic cycle beyond the chemical step.

Robust identification of interactions between heat-stress responsive genes in the chicken brain using Bayesian networks and augmented expression data.

Bayesian networks represent a useful tool to explore interactions within biological systems. The aims of this study were to identify a reduced number of genes associated with a stress condition in chickens (Gallus gallus) and to unravel their interactions by implementing a Bayesian network approach. Initially, one publicly available dataset (3 control vs. 3 heat-stressed chickens) was used to identify the stress signal, represented by 25 differentially expressed genes (DEGs). The dataset was augmented by looking for the 25 DEGs in other four publicly available databases. Bayesian network algorithms were used to discover the informative relationships between the DEGs. Only ten out of the 25 DEGs displayed interactions. Four of them were Heat Shock Proteins that could be playing a key role, especially under stress conditions, where maintaining the correct functioning of the cell machinery might be crucial. One of the DEGs is an open reading frame whose function is yet unknown, highlighting the power of Bayesian networks in knowledge discovery. Identifying an initial stress signal, augmenting it by combining other databases, and finally learning the structure of Bayesian networks allowed us to find genes closely related to stress, with the possibility of further exploring the system in future studies.

The association between patient preoperative disposition and outcomes after diagnostic lung biopsy.

Background: Surgical diagnostic lung biopsy (DLB) is performed to guide the management of pulmonary disease with unclear etiology. However, the utilization of surgical DLB in critically ill patients remains unclear. The purpose of this study was to determine if patient preoperative disposition impacts complication rates after DLB. Methods: This was retrospective cohort study using electronic health record (EHR) data at one academic institution [2013-2021]. Patients who underwent DLB were identified using current procedural terminology (CPT) codes and cohorted based on preoperative disposition. The primary outcome was 30-day mortality; secondary outcomes were overall morbidity, individual complications, and changes to medical therapy. Complication rates were compared using chi-squared tests, Fisher's exact tests, or analysis of variance (ANOVA). Multivariable logistic regression was performed to generate risk-adjusted odds ratios (ORs) for each complication. Results: Of 285 patients, 238 (83.5%) presented from home, 26 (9.1%) from inpatient floor units, and 21 (7.4%) from intensive care units (ICUs). Patients requiring ICU had the highest 30-day rates of mortality, overall morbidity, and all individual complications (all P<0.05). After risk adjustment, non-ICU inpatients had higher odds of postoperative ventilator use, prolonged ventilation, and ICU need than outpatients (all P<0.05). Preoperative ICU disposition was associated with increased OR of 30-day mortality [OR, 70.92; 95% confidence interval (CI): 5.55-906.32] and overall morbidity (OR, 7.27; 95% CI: 1.93-27.42) compared to patients with other preoperative dispositions. There were no differences in changes to medical therapy between the cohorts. Conclusions: Patients requiring ICU before DLB had significantly higher risk-adjusted rates of mortality and postoperative complications than outpatients and other inpatients. A clear benefit from tissue diagnosis should be defined prior to performing DLB on critically ill patients.

Effect of a non-reactive absorbent with or without environmentally oriented electronic feedback on anesthesia provider's fresh gas flow rates: A greening initiative.

STUDY OBJECTIVE: To examine the effects of a non-reactive carbon dioxide absorbent (AMSORB® Plus) versus a traditional carbon dioxide absorbent (Medisorb™) on the FGF used by anesthesia providers and an electronic educational feedback intervention using Carestation™ Insights (GE HealthCare) on provider-specific change in FGF. DESIGN: Prospective, single-center cohort study set in a greening initiative. SETTING: Operating room. PARTICIPANTS: 157 anesthesia providers (i.e., anesthesiology trainees, certified registered nurse anesthetists, and solo anesthesiologists). INTERVENTIONS: Intervention #1 was the introduction of AMSORB® Plus into 8 Aisys CS2, Carestation™ Insights-enabled anesthesia machines (GE HealthCare) at the study site. At the end of week 6, anesthesia providers were educated and given an environmentally oriented electronic feedback strategy for the next 12 weeks of the study (Intervention #2) using Carestation™ Insights data. MEASUREMENTS: The dual primary outcomes were the difference in average daily FGF during maintenance anesthesia between machines assigned to AMSORB® Plus versus Medisorb™ and the provider-specific change in average fresh gas flows after 12 weeks of feedback and education compared to the historical data. MAIN RESULTS: Over the 18-week period, there were 1577 inhaled anesthetics performed in the 8 operating rooms (528 for intervention 1, 1049 for intervention 2). There were 1001 provider days using Aisys CS2 machines and 7452 provider days of historical data from the preceding year. Overall, AMSORB® Plus was not associated with significantly less FGF (mean - 80 ml/min, 97.5% confidence interval - 206 to 46, P = .15). The environmentally oriented electronic feedback intervention was not associated with a significant decrease in provider-specific mean FGF (-112 ml/min, 97.5% confidence interval - 244 to 21, P = .059). CONCLUSIONS: This study showed that introducing a non-reactive absorbent did not significantly alter FGF. Using environmentally oriented electronic feedback relying on data analytics did not result in significantly reduced provider-specific FGF.

Unprofessionalism in anesthesiology: A qualitative study on classifying unprofessional behavior in anesthesiology residency education.

STUDY OBJECTIVE: This study aims to identify the domains that constitute behaviors perceived to be unprofessional in anesthesiology residency training programs. DESIGN: Qualitative study. SETTING: Anesthesiology residency training programs. PATIENTS: Not applicable. The participants involved residents, fellows, and faculty members purposefully sampled in four US-based anesthesiology residency programs. INTERVENTIONS: Participants were asked to submit examples of unprofessional behavior they witnessed in anesthesiology residents, fellows, or faculty members via a Qualtrics link. MEASUREMENTS: Not applicable. The behavior examples were independently reviewed and categorized into themes using content analysis. MAIN RESULTS: A total of 116 vignettes were collected, resulting in a final list of 111 vignettes after excluding those that did not describe behavior exhibited by anesthesiology faculty or trainees. Fifty-eight vignettes pertained to unprofessional behaviors observed in faculty members and 53 were observed in trainees (residents and fellows). Nine unprofessionalism themes emerged in the analysis. The most common themes were VERBAL, SUPERVISION, QUALITY, ENGAGEMENT, and TIME. As to the distribution of role group (faculty versus trainee) by theme, unprofessional behaviors falling into the categories of BIAS, GOSSIP, LEWD, and VERBAL were observed more in faculty; whereas themes with unprofessional behavior primarily attributed to trainees included ENGAGEMENT, QUALITY, TIME, and SUPERVISION. CONCLUSION: By reviewing reported professionalism-related vignettes within residency training programs, we identified classification descriptors for defining unprofessional behavior specific to anesthesiology residency education. Findings from this study enrich the definition of professionalism as a multi-dimensional competency pertaining to anesthesiology graduate medical education. This framework may facilitate preventative intervention and timely remediation plans for unprofessional behavior in residents and faculty.

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.

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.

Pain management in victims of disasters.

Pain is widely studied and is considered a major clinical, social, and economic problem worldwide, although it remains poorly understood. For disaster victims, the complex picture, biologically, psychologically, and socially, only makes the situation even more complicated. This narrative review aims to describe specific aspects of pain and pain management in disaster victims. We reviewed relevant literature, both on pain management and selected specific data related to conflict victims. We discuss the complexity of the picture, its different aspects, and mechanisms. We discuss the limitations of current approaches and propose a simple strategy, including mitigation plans, all illustrated by a case study based on a personal experience in the Gaza Strip in 2022. The vulnerability factors are well known, as well as the tangle of intense acute pain and the persistence of pain in the subacute and chronic phase. However, the management of acute pain is, in a disaster context, more constrained than chosen. Empirical evidence suggests a focus on modifiable risk factors as well as the evaluation of strategies guiding future management. This management may depend on obstacles and barriers, linked to the context of the disaster, the availability of medicines, techniques, skills as well as linguistic and cultural barriers. Our proposal includes systematic assessment and, in a later phase, tailored and personalized treatment. In the chronic phase of rehabilitation and follow-ups, the essential place for management of psychological and social aspects become predominant. In disaster areas, including during and after conflict, the management, and recommendations for the management of acute and chronic pain are complex, distinct but interdependent. Acute pain must be systematically assessed and treated while personalized care pathways are desirable at a later stage. Psychological and social considerations are essential. Data collection should be systematically considered.

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.

Timing of recovery of quality of life after robotic anatomic lung resection.

Patient-reported outcomes (PROs) are an underreported aspect of surgical recovery. The purpose of our study was to track PROs after robotic anatomic lung to determine the timing to recovery of baseline patient baseline quality of life. This was a prospective cohort study at an academic medical center (4/2021-12/2022). Patients who underwent robotic anatomic lung resection were asked to complete PROMIS-29 surveys at the preoperative clinic visit, postoperative clinic visit, 30 days and 90 days postoperatively via in-person and email-based electronic surveys. The PROPr score, a summary of health-related quality of life, and mental and physical health z-scores were estimated for each patient using published methods and compared by postoperative timing. 75 patients completed the preoperative survey and at least one postoperative survey; 56 completed postoperative clinic surveys, 54 completed 30-day postoperative surveys, and 40 completed 90-day postoperative surveys. All three PROMIS scores decreased between the preoperative and first postoperative visit (all p < 0.05). PROPr scores increased over time but remained significantly worse than baseline by 90 days (-0.08 difference between 90 days and preoperative, p = 0.02). While PROMIS summary z-scores for physical health remained - 0.29 lower at 90 days postoperatively, this did not reach statistical significance (p = 0.06). Mental health scores returned to baseline by 90 days postoperatively (p = 0.41). While some PROs returned to baseline by 90 days postoperatively, overall quality-of-life scores remained significantly below preoperative baselines. These findings are important to share with patients during the informed consent process to achieve patient centered care more effectively.

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.

The Effect of Social Vulnerability on Initial Stage and Treatment for Non-Small Cell Lung Cancer.

OBJECTIVE: The Social Vulnerability Index (SVI) is a composite metric for social determinants of health. The objective of this study was to determine if SVI influences stage at presentation for non-small cell lung cancer (NSCLC) patients and subsequent therapies. MATERIALS AND METHODS: NSCLC patients from our local contribution to the National Cancer Database (2011-2021) were grouped into low SVI (<75 %ile) and high SVI (>75 %ile) cohorts. Demographics, cancer-related variables, and treatment modalities were compared. Multivariable logistic regression was performed to control for the impact of demographics on cancer presentation and for the impact of oncologic variables on treatment outcomes. RESULTS: Of 1,662 NSCLC patients, 435 (26 %) were defined as high SVI. Compared to the 1,227 (74 %) low SVI patients, highly vulnerable patients were more likely to be male (53.3 % vs 46.0 %, p = 0.009), non-White (17.2 % vs 9.7 %, p < 0.0001), have comorbidities (29.4 % vs 23.1 %, p = 0.009) and present at a higher AJCC clinical T, M and overall stage (all p < 0.05). These findings persisted on multivariable analysis, with highly vulnerable patients having 1.5x the odds (95 %CI: 1.23-1.86, p < 0.001) of presenting at more advanced stage. Patients with high SVI were less likely to be recommended for and receive surgery (40.9 % vs 53.2 %, p < 0.001), and this finding persisted after controlling for stage at presentation (OR 1.37, 95 %CI 1.04-1.80). CONCLUSIONS: Highly vulnerable patients present at a more advanced clinical stage and are less likely to be recommended and receive surgery, even after controlling for stage at presentation. Further investigation into these findings is warranted to achieve more equitable oncologic care.

Emerging data in COVID-19 create urgent challengers for health providers: Updates on COVID-19 vaccine and Paxlovid.

In this original research we present new emerging data in COVID-19 that create urgent challenges for health providers in prevention and treatment. Health providers should be aware that COVID-19 cases, hospitalizations, and deaths have increased markedly in August 2023. Further, recent data demonstrate a new emerging strain resistant to prior natural and vaccine immunity. The most recent emerging data show that only this updated COVID-19 vaccine produces the same immune response as previous vaccines that reduced mortality by over 95 % and morbidity by over 99 %. This recommendation encompasses all adults and children aged 6 months and older, regardless of whether they have had a prior COVID-19 infection or even if they have never received a prior vaccination. This updated COVID-19 vaccine, approved in September 2023, will be the best means to prevent COVID-19 during this upcoming season of respiratory viruses. In the meanwhile, all members of the US population regardless of previous natural infection, vaccines, or boosters are equally susceptible. At present, health providers should counsel all their patients about masking, social distancing, and avoiding crowds, especially indoors where regions of extreme weather conditions are keeping people indoors in closed quarters. In the treatment of COVID-19 the major clinical challenge to health providers, especially in their Black patients, is to prescribe Paxlovid during the first 5 days after onset of symptoms and a positive test.

Secondary Analysis of the Rate of Second Primary Lung Cancer From Cancer and Leukemia Group B 140503 (Alliance) Trial of Lobar Versus Sublobar Resection for T1aN0 Non-Small-Cell Lung Cancer.

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical trial updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.Patients with early-stage non-small-cell lung cancer (NSCLC) who undergo curative surgical resection are at risk for developing second primary lung cancer (SPLC). Cancer and Leukemia Group B 140503 (Alliance) was a multicenter, international, randomized, phase III trial in patients with stage T1aN0 NSCLC (using the TNM staging system seventh edition) and demonstrated the noninferiority for disease-free survival between sublobar resection (SLR) and lobar resection (LR). After surgery, patients underwent computed tomography surveillance as defined by the protocol. The determination of a SPLC was done by the treating physician and recorded in the study database. We performed an analysis of the rate of SPLC (per patient per year) and the 5-year cumulative incidence in the study population and within the SLR and LR arms. Median follow-up was 7 years. The rate per patient per year in the study population, in the SLR arm, and in the LR arm was 3.4% (95% CI, 2.9 to 4.1), 3.8% (95% CI, 2.9 to 4.9), and 3.1% (95% CI, 2.4 to 4.1), respectively. The estimated 5-year cumulative incidence of SPLC in the study population, SLR arm, and LR arm was 15.9% (95% CI, 12.9 to 18.9), 17.2% (95% CI, 12.7 to 21.5), and 14.7% (95% CI, 10.6 to 18.7), respectively.

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.

The Society of Thoracic Surgeons General Thoracic Surgery Database: 2023 Update on Outcomes and Research.

The Society of Thoracic Surgeons General Thoracic Surgery Database (GTSD) continues its trajectory of growth and enhancement, solidifying its stature as a premier global thoracic surgical database. The past year witnessed a notable expansion with the inclusion of 10 additional participating sites, now totaling 287, augmenting the database's repository to more than 800,000 procedures. A significant stride was made in refining the data audit process, thereby elevating the accuracy and completeness metrics, a testament to the relentless pursuit of data integrity. The GTSD further broadened its research apparatus, with 15 scholarly publications, a 50% uptick from the preceding year. These publications underscore the database's instrumental role in advancing thoracic surgical knowledge. In a concerted effort to alleviate data entry exigencies, the GTSD Task Force also instituted streamlined data submission protocols, a move lauded by participant sites. This report delineates the recent advancements, volume trajectories, and outcome metrics and encapsulates the prolific research output emanating from the GTSD, reflecting a year of substantial progress and academic fecundity.

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.

National trends in technique use for esophagectomy: Does primary surgeon specialty matter?

BACKGROUND: Cardiothoracic surgeons and general surgeons (including surgical oncologists) perform most esophagectomies. The purpose of this study was to explore whether specialty-driven differences in surgical techniques and the use of minimally invasive surgical approaches exist and are associated with postoperative outcomes after esophagectomy. METHODS: This was a retrospective review of the American College of Surgeons National Surgical Quality Improvement Program esophagectomy-targeted participant user file (2016-2018). Patients who underwent esophagectomy were sorted into cardiothoracic and general surgeon cohorts based on surgeon specialty. Perioperative characteristics and postoperative outcomes were compared using the χ2 analysis or independent t test. Multivariable logistic regression controlling for perioperative variables was performed to generate risk-adjusted rates of postoperative outcomes compared by surgical specialty. RESULTS: Of 3,247 patients included, 1,792 (55.2%) underwent esophagectomy by cardiothoracic surgeons and 1,455 (44.5%) by general surgeons as the primary surgeon. Cardiothoracic surgeons were more likely to use traditional minimally invasive surgical (P = .0004) or open approaches (P < .0001) and less likely to use robotic (P = .04) or a hybrid robotic and traditional approaches (P < .0001). Cardiothoracic surgeons performed more Ivor Lewis esophagectomies and fewer transhiatal and McKeown esophagectomies (P < .0001). After risk adjustment, there were no differences in rates of postesophagectomy complications, such as anastomotic leaks or positive margins, between cardiothoracic surgeons and general surgeons (all P > .05). However, cardiothoracic surgeons were more likely than general surgeons to treat anastomotic leaks with surgery rather than procedural interventions (odds ratio = 1.76; 95% confidence interval, 1.24-2.52). CONCLUSION: Cardiothoracic surgeons and general surgeons use minimally invasive surgical subtypes differently when performing esophagectomy. However, there were no risk-adjusted differences in postoperative complications when compared by surgical subspecialty. Esophagectomy is being performed safely by surgeons with different specialties and training pathways.