Search

Xiao Wu,1 Don Hayes Jr,2,3 Joseph B Zwischenberger,4 Robert J Kuhn,5 Heidi M Mansour1,61University of Kentucky, College of Pharmacy, Department of Pharmaceutical Sciences-Drug Development Division, Lexington, KY, USA; 2The Ohio State University College of Medicine, Departments of Pediatrics and Internal Medicine, Lung and Heart-Lung Transplant Programs, Nationwide Children's Hospital, Columbus, OH, USA; 3The Ohio State University College of Medicine, The Davis Heart and Lung Research Institute, Columbus, OH, USA; 4University of Kentucky College of Medicine, Departments of Pediatrics, Biomedical Engineering, Diagnostic Radiology, and Surgery, Lexington, KY, USA; 5University of Kentucky, College of Pharmacy, Division of Pharmacy Practice and Science, Lexington, KY, USA; 6University of Kentucky, Center of Membrane Sciences, Lexington, KY, USAAbstract: The aim of this study was to design, develop, and optimize respirable tacrolimus microparticles and nanoparticles and multifunctional tacrolimus lung surfactant mimic particles for targeted dry powder inhalation delivery as a pulmonary nanomedicine. Particles were rationally designed and produced at different pump rates by advanced spray-drying particle engineering design from organic solution in closed mode. In addition, multifunctional tacrolimus lung surfactant mimic dry powder particles were prepared by co-dissolving tacrolimus and lung surfactant mimic phospholipids in methanol, followed by advanced co-spray-drying particle engineering design technology in closed mode. The lung surfactant mimic phospholipids were 1,2-dipalmitoyl-sn-glycero-3-phosphocholine and 1,2-dipalmitoyl-sn-glycero-3-[phosphor-rac-1-glycerol]. Laser diffraction particle sizing indicated that the particle size distributions were suitable for pulmonary delivery, whereas scanning electron microscopy imaging indicated that these particles had both optimal particle morphology and surface morphology. Increasing the pump rate percent of tacrolimus solution resulted in a larger particle size. X-ray powder diffraction patterns and differential scanning calorimetry thermograms indicated that spray drying produced particles with higher amounts of amorphous phase. X-ray powder diffraction and differential scanning calorimetry also confirmed the preservation of the phospholipid bilayer structure in the solid state for all engineered respirable particles. Furthermore, it was observed in hot-stage micrographs that raw tacrolimus displayed a liquid crystal transition following the main phase transition, which is consistent with its interfacial properties. Water vapor uptake and lyotropic phase transitions in the solid state at varying levels of relative humidity were determined by gravimetric vapor sorption technique. Water content in the various powders was very low and well within the levels necessary for dry powder inhalation, as quantified by Karl Fisher coulometric titration. Conclusively, advanced spray-drying particle engineering design from organic solution in closed mode was successfully used to design and optimize solid-state particles in the respirable size range necessary for targeted pulmonary delivery, particularly for the deep lung. These particles were dry, stable, and had optimal properties for dry powder inhalation as a novel pulmonary nanomedicine.Keywords: dry powder inhaler (DPI), pulmonary nanomedicine, lung transplant, immunosuppression, lung surfactant, phospholipid colloidal self-assemblies, solid-state particle engineering design, organic solution advanced spray drying

Objective: To examine outcomes in patients who receive small amounts of intraoperative blood transfusion. Design: Longitudinal, uncontrolled observational study evaluating results of intraoperative transfusion in patients entered into the American College of Surgeons National Surgical Quality Improvement Program database. We made propensity-matched comparisons between patients who received and did not receive intraoperative transfusion to minimize confounding when estimating the effect of intraoperative transfusion on postoperative outcomes. Setting: We queried the American College of Surgeons National Surgical Quality Improvement Program database for patients undergoing operations between January 1, 2005, and December 31, 2009. Patients: A large sample of surgical patients from 173 hospitals throughout the United States. Main Outcome Measures: Operative mortality and serious perioperative morbidity (⩾1 of 20 complications). Results: After exclusions, 941 496 operations were analyzed in patients from 173 hospitals. Most patients (893 205 patients [94.9%]) did not receive intraoperative transfusions. Patients who received intraoperative infusion of 1 unit of packed red blood cells (15 186 patients [1.6%]) had higher unadjusted rates of mortality and more serious morbidity. These rates further increased with intraoperative transfusion of more than 1 unit of packed red blood cells in a dose-dependent manner. After propensity matching to adjust for multiple preoperative risks, transfusion of a single unit of packed red blood cells increased the multivariate risk of mortality, wound problems, pulmonary complications, postoperative renal dysfunction, systemic sepsis, composite morbidity, and postoperative length of stay compared with propensity-matched patients who did not receive intraoperative transfusion. Conclusions: There is a dose-dependent adverse effect of intraoperative blood transfusion. It is likely that a small, possibly discretionary amount of intraoperative transfusion leads to increased mortality, morbidity, and resource use, suggesting that caution should be used with intraoperative transfusions for mildly hypovolemic or anemic patients. [ABSTRACT FROM AUTHOR]

Tracheoinnominate fistula (TIF) is a rare condition with significant potential for mortality if surgical intervention is not immediate. We present two cases of successfully managed TIF. Both cases involve ligation and resection of the innominate artery at the TIF followed by a pectoralis major muscle flap. In both cases, success was largely due to a high index of suspicion and immediate control of the bleeding with transport to the operating room for surgical repair. The history, aetiology, and pathogenesis of TIF are reviewed, yielding an algorithm for recommended management of TIF. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Acute respiratory failure is complicated by acidosis and altered end-organ perfusion. NOVA-LUNG iLA is an interventional lung assist (ILA) device for arteriovenous carbon dioxide removal (AVCO2R). The present study was conducted to evaluate the device for short-term CO2 removal performance and hemodynamic response. METHODS: Six adult sheep received cannulation of the jugular vein and carotid artery. The ILA-AVCO2R circuit was placed on the sheep for 72 hours. Hemodynamics and PaCO2 were measured; CO2 removal was calculated while varying sweep gas flow rates (Qg), device blood flow rates (Qb), and PaCO2. RESULTS: Hemodynamic variables remained normal throughout the 72 hour study. CO2 removal increased with increases in Qg or Qb. Mean CO2 removal was 119.3 ml/min for Qb 1 L/ min, Qg 5 L/min, and PaCO2 40-50 mmHg. PaCO2 was directly proportional to CO2 clearance (R=0.72, p <0.001). CONCLUSION: NOVALUNG iLA can provide near total CO2 removal with Qb 1-2 L/min, Qg 5 L/min, and minimal flow resistance (3.88+/-0.82 mmHg/L/min). PaCO2 correlates with CO2 removal and is dependent on Qb and Qg. [ABSTRACT FROM AUTHOR]

To ascertain current anticoagulation management during neonatal extracorporeal membrane oxygenation (ECMO), a telephone survey was undertaken of all active ECMO (n = 81, 100% response rate) centres in the USA. Hospital policies regarding federal regulations governing laboratory tests [Clinical Laboratory Improvement Amendment (CLIA) 1988] were determined along with specific patient anticoagulation strategies and use of specific activated coagulation time (ACT) equipment. More than 90% of the respondents use the Hemochron device (International Technidyne Corp, Edison, NJ, USA) while the remaining centres use the Hemotec device Medtronic Hemotec, Inc, Englewood, CO, USA). Quality control (QC) testing is performed by most centres, but there is no consensus regarding frequency of testing nor methods for dealing with abnormal results. Nearly one-half of the centres use beef lung-derived heparin and the other half use porcine intestinal-derived heparin. One-half of the programmes had a minimum heparin dose despite the ACT value, but the range varied significantly. Four out of five respondents reported that heparin dosages were dictated strictly by ACT results, and 63% will temporarily stop heparin administration for high ACT results, bleeding and/or surgery. Approximately one-third of the centres perform proficiency testing of the equipment in compliance with CLIA 1988. In conclusion, there appears to be no consensus regarding commitment to a QC programme among active ECMO centres. [ABSTRACT FROM AUTHOR]

The manufacturing process of Regulatory T (Treg) cells for clinical application begins with the positive selection of CD25 + cells using superparamagnetic iron-oxide nanoparticle (SPION)-conjugated anti-CD25 antibodies (spCD25) and immunomagnetic cell separation technology. Our findings revealed that the interaction of spCD25 with its cell target induced the internalization of the complex spCD25-Interleukin-2 Receptor. Accumulation of intracellular spCD25 triggered oxidative stress, causing delayed Treg expansion and temporary reduction in suppressor activity. This activation delay hindered the efficient generation of clinically competent cells. During this early phase, Treg cells exhibited elevated mitochondrial superoxide and lipid peroxidation levels, with concomitant decrease on mitochondrial respiration rates. The results uncovered the increased mitochondrial unfolded protein response (mitoUPR). This protective, redox-sensitive activity is inherent of Tregs when contrasted with homologous, spCD25-treated, conventional T cells. While the temporary effects of spCD25 on clinically competent cells did not impede their use in a safety/feasibility pilot study with kidney transplant recipients*, it is reasonable to anticipate a potential reduction in their therapeutic efficacy. The mechanistic understanding of the adverse effects triggered by spCD25 is crucial for improving the manufacturing process of clinically competent Treg cells, a pivotal step in the successful implementation of immune cell therapy in transplantation. *Clinical trial registration number NCT03284242 at ClinicalTrials.gov., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Background: Workplace-based assessment (WBA) can facilitate evaluation of operative performance; however, implementation of WBA is sometimes unsuccessful. The American Board of Surgery Entrustable Professional Activities WBA project was launched in July 2023. Some programs will face the challenge of re-implementation of a WBA following previous failures. It is unknown what interventions are most effective for WBA re-implementation. Our goal is to identify barriers and facilitators to re-implementing SIMPL, an operative performance WBA., Methods: The System for Improving and Measuring Procedural Learning (SIMPL) was implemented at our residency in 2018, but usage rates were low. We interviewed residents and faculty to identify barriers to usage and opportunities for improvement. Residents reported that SIMPL usage declined because of several factors, including a low faculty response rate, while some faculty reported not responding because they were unable to login to the app and because usage was not mandated. We then re-implemented SIMPL using a plan based on Kotter's Model of Change. To evaluate impact, we analyzed rates of SIMPL usage when it was first implemented, as well as before and after the date of re-implementation., Results: In September 2022, we re-implemented SIMPL at our program with measures addressing the identified barriers. We found that, in the six months after re-implementation, an average of 145.8 evaluations were submitted by residents per month, compared with 47 evaluations per month at the start of the original implementation and 5.8 evaluations per month just prior to re-implementation. Faculty completed 60.6% of evaluations and dictated feedback for 59.1% of these evaluations, compared with 69.1% at implementation (44% dictated) and 43% prior to re-implementation (53% dictated)., Conclusions: After identifying barriers to implementation of a WBA, we re-implemented it with significantly higher usage by faculty and residents. Future opportunities exist to implement or re-implement assessment tools within general surgery programs. These opportunities may have a significant impact in the setting of national standardization of workplace-based assessment among general surgery residencies., (© 2024. The Author(s).)

Objective: We sought to determine the impact of right ventricular dysfunction on the outcomes of mechanically ventilated patients with COVID-19 requiring veno-venous extracorporeal membrane oxygenation., Methods: Six academic centers conducted a retrospective analysis of mechanically ventilated patients with COVID-19 stratified by support with veno-venous extracorporeal membrane oxygenation during the first wave of the pandemic (March to August 2020). Echocardiograms performed for clinical indications were reviewed for right and left ventricular function. Baseline characteristics, hospitalization characteristics, and survival were compared., Results: The cohort included 424 mechanically ventilated patients with COVID-19, 126 of whom were cannulated for veno-venous extracorporeal membrane oxygenation. Right ventricular dysfunction was observed in 38.1% of patients who received extracorporeal membrane oxygenation and 27.4% of patients who did not receive extracorporeal membrane oxygenation with an echocardiogram. Biventricular dysfunction was observed in 5.5% of patients who received extracorporeal membrane oxygenation. Baseline patient characteristics were similar in both the extracorporeal membrane oxygenation and non-extracorporeal membrane oxygenation cohorts stratified by the presence of right ventricular dysfunction. In the extracorporeal membrane oxygenation cohort, right ventricular dysfunction was associated with increased inotrope use (66.7% vs 24.4%, P < .001), bleeding complications (77.1% vs 53.8%, P = .015), and worse survival independent of left ventricular dysfunction (39.6% vs 64.1%, P = .012). There was no significant difference in days ventilated before extracorporeal membrane oxygenation, length of hospital stay, hours on extracorporeal membrane oxygenation, duration of mechanical ventilation, vasopressor use, inhaled pulmonary vasodilator use, infectious complications, clotting complications, or stroke. The cohort without extracorporeal membrane oxygenation cohort demonstrated no statistically significant differences in in-hospital outcomes., Conclusions: The presence of right ventricular dysfunction in patients with COVID-19-related acute respiratory distress syndrome supported with veno-venous extracorporeal membrane oxygenation was associated with increased in-hospital mortality. Additional studies are required to determine if mitigating right ventricular dysfunction in patients requiring veno-venous extracorporeal membrane oxygenation improves mortality., (Published by Elsevier Inc.)

Competing Interests: Disclosure: The authors have no conflicts of interest to report.

Over the past decade, medical education has shifted from a time-based approach to a competency-based approach for surgical training. This transition presents many new systemic challenges. The Society for Improving Medical Professional Learning (SIMPL) was created to respond to these challenges through coordinated collaboration across an international network of medical educators. The primary goal of the SIMPL network was to implement a workplace-based assessment and feedback platform. To date, SIMPL has developed, implemented, and sustained a platform that represents the earliest and largest effort to support workplace-based assessment at scale. The SIMPL model for collaborative improvement demonstrates a potential approach to addressing other complex systemic problems in medical education., Competing Interests: J.B.Z., S.S.S.-S., and B.C.G. have leadership positions, contracts, and grants with SIMPL. The remaining authors declare that they have nothing to disclose., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Objective: We sought to determine the influence of venovenous extracorporeal membrane oxygenation (ECMO) on outcomes of mechanically ventilated patients with COVID-19 during the first 120 days after hospital discharge., Methods: Five academic centers conducted a retrospective analysis of mechanically ventilated patients with COVID-19 admitted during March through May 2020. Survivors had access to a multidisciplinary postintensive care recovery clinic. Physical, psychological, and cognitive deficits were measured using validated instruments and compared based on ECMO status., Results: Two hundred sixty two mechanically ventilated patients were compared with 46 patients cannulated for venovenous ECMO. Patients receiving ECMO were younger and traveled farther but there was no significant difference in gender, race, or body mass index. ECMO patients were mechanically ventilated for longer durations (median, 26 days [interquartile range, 19.5-41 days] vs 13 days [interquartile range, 7-20 days]) and were more likely to receive inhaled pulmonary vasodilators, neuromuscular blockade, investigational COVID-19 therapies, blood transfusions, and inotropes. Patients receiving ECMO experienced greater bleeding and clotting events (P < .01). However, survival at discharge was similar (69.6% vs 70.6%). Of the 217 survivors, 65.0% had documented follow-up within 120 days. Overall, 95.5% were residing at home, 25.7% had returned to work or usual activity, and 23.1% were still using supplemental oxygen; these rates did not differ significantly based on ECMO status. Rates of physical, psychological, and cognitive deficits were similar., Conclusions: Our data suggest that COVID-19 survivors experience significant physical, psychological, and cognitive deficits following intensive care unit admission. Despite a more complex critical illness course, longer average duration of mechanical ventilation, and longer average length of stay, patients treated with venovenous ECMO had similar survival at discharge and outcomes within 120 days of discharge., (Published by Elsevier Inc.)

We are developing a clinically practical percutaneous double lumen cannula (DLC)-based cavopulmonary assist (CPA) system to support failing Fontan patients. In this study, our CPA DLC was redesigned for even blood flow, minimal recirculation, and easy insertion/deployment. After bench testing, this new CPA system was evaluated for 4 hours (n = 10) and 96 hours (n = 5) in our clinically relevant lethal cavopulmonary failure (CPF) sheep model for ease of cannulation/deployment, reversal of CPF hemodynamics/end-organ hypoperfusion, and durability/biocompatibility. Cavopulmonary failure was achieved in all sheep. All DLCs were successfully inserted/deployed into Fontan anatomy. Cavopulmonary assist reversed CPF with normalized central venous pressure and cardiac output. All survival sheep were ambulatory with normal eating/drinking. One sheep was euthanized after 6 hours from cannula kinking, and one sheep died of hypokalemia after 8 hours. Three sheep survived 96 hours with normal hemodynamics. Free hemoglobin was only 3.7 ± 1.2 mg/dl at 96 hours, indicating negligible hemolysis. Creatinine, blood urea nitrogen, and lactate increased from hypoperfusion but normalized by 72 hours CPA. Necropsy showed only a small, immobilized thrombus ring at umbrella attachment to DLC. Our DLC-based system provided total ambulatory CPA in a lethal CPF sheep model with 96 hour survival and complete reversal of hemodynamics and end-organ hypoperfusion., Competing Interests: Disclosure: D.W. and J.B.Z. are co-owners of W-Z Biotech, LLC and they also receive royalties from the Getinge Group for their patented Avalon Elite. D.W. and C.B.-C. are part-time employees of W-Z Biotech, LLC. D.M. is a consultant/proctor/speaker for Abbott, Syncardia, Berlin, and Medtronic. The other authors have no conflicts of interest to report., (Copyright © ASAIO 2023.)

Objective: Upwards of 79%-88% of practicing surgeons report musculoskeletal pain due to operating. However, little is known about when these issues begin to become clinically significant. This survey evaluates the prevalence and impact of musculoskeletal pain among surgical residents., Design: After IRB approval, an anonymous 19-question survey based on Cornell Musculoskeletal Discomfort Questionnaire was sent to current surgical residents measuring frequency and degree of pain at 5 sites (neck, shoulder, upper back, lower back, and elbow/wrist) as well as impact on activities both at work and outside of work. Chi square analysis was used to identify differences between groups., Setting: Single academic medical center., Participants: Trainees in all surgical-based specialties., Results: Fifty-three residents responded from 8 different specialties (38% response rate). Respondents were a representative balance of male (53%)/female (47%) with a mean age of 30 ± 2 years. Residents in all specialties and all years of clinical training responded, with the greatest number from general surgery (the largest program with 48% of respondents), second year of clinical training (30%) and an overwhelming 96% of residents reported experiencing pain they felt was due to operating. The most common sites of pain were the neck (92%) and lower back (77%). This pain was a frequent issue for most with 74% reporting multiple times per month and 26% reporting pain nearly every day. Nearly half of residents reported that pain slightly to substantially interfered with their ability to work (44%) and with activities outside of work (47%). Most residents (75%) sought no treatment. No residents missed work despite reporting pain., Conclusions: Musculoskeletal pain begins during training, occurs regularly, and affects function. Neck pain is the most frequent, severe, and disabling site. This provides a target for interventions to reduce the impact of chronic pain on patient care, surgeon wellness, and career longevity., (Copyright © 2023 Association of Program Directors in Surgery. Published by Elsevier Inc. All rights reserved.)

Background: Although all congenital heart defects (CHD) present unique challenges, univentricular CHD are especially challenging given the difficulty of passively perfusing pulmonary blood flow. Three surgical procedures are required within the first years of life, with the final completing a Fontan circulation in which the inferior vena cava is connected to the pulmonary artery and previously connected superior vena cava. This allows passive venous return to the pulmonary circulation then flow into the single ventricle for systemic circulation., Methods: Although a Fontan provides successful palliation for two to three decades, many complications can arise as pulmonary resistance must remain low to allow adequate forward flow. Eventually, the failing Fontan circulation requires temporary support as the patient awaits a heart transplant. We reviewed PubMed, Google Scholar, and U. Kentucky library for different techniques evaluated to support a failing Fontan circulation., Results: Multiple technologies have been developed as a bridge to transplant to decrease morbidity. Innovative types of extracorporeal membrane oxygenation, ventricular assist devices, and total artificial hearts have been attempted in laboratory settings as well as in Fontan patients with varying degrees of success. This article emphasizes the strengths and weaknesses of each technology in the context of Fontan physiology., Conclusion: The end game for these patients remains a heart transplant. Without easy access to donors, each of the options discussed is a potential bridge to limit morbidity and mortality until a suitable donor heart becomes available., (© 2022 Wiley Periodicals LLC.)

Objective: The aims of this study were to determine whether physical rehabilitation intervention for individuals who required extracorporeal membrane oxygenation (ECMO) is associated with clinical outcomes and to assess whether the patient mobility response over initial rehabilitation sessions early in the intensive care unit (ICU) course predicts or is associated with survival, lengths of stay, discharge disposition, and 30-day readmissions., Methods: This study was a 10-year retrospective practice analysis of adults who were critically ill and required ECMO for >72 hours in the cardiothoracic ICU at an academic medical center. Physical rehabilitation implemented during or following the initiation of ECMO was quantified on the basis of timing, frequency, and change in mobility level in response to the intervention over the first 4 consecutive sessions. The primary dependent outcome was in-hospital mortality. Secondary outcomes included 30-day readmission and discharge disposition ranked on an ordinal scale., Results: Three hundred fifteen individuals (mean age = 50 years [SD = 15 years]; 63% men; mean Sequential Organ Failure Assessment score = 11.6 [SD = 3.3]) met the inclusion criteria. Two hundred eighteen individuals (69%) received at least 1 physical rehabilitation session while requiring ECMO, 70 (22%) received rehabilitation after ECMO was discontinued, and 27 (9%) never received rehabilitation. Individuals discharged alive achieved higher mobility levels and had a steeper, more positive rate of change in mobility over the first 4 sessions than individuals who died in the hospital (2.8 vs 0.38; degrees of freedom = 199, t = 8.24). Those who received rehabilitation and achieved the milestones of sitting on the edge of the bed and walking for >45 m were more likely to survive (47% vs 13%; χ2 = 156) than those who did not (26% vs 3.5%; χ2 = 80)., Conclusion: A positive rate of change in mobility and the ability to achieve mobility milestones with rehabilitation were associated with improved clinical outcomes., Impact: An individual's mobility response to physical rehabilitation early in the ICU course is an important indicator of illness and should be used with clinical presentation to guide clinical decision-making and predict outcomes., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Physical Therapy Association. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Ambulatory extracorporeal membrane oxygenation (ECMO) has shown promise as a bridge to lung transplantation. The primary goal of ambulatory ECMO is to provide enough gas exchange to allow patients to participate in preoperative physical therapy. Various strategies of ambulatory ECMO are utilized depending upon patients' need. A wide spectrum of ECMO configurations is available to tackle this situation. We discuss those configurations in this article., Competing Interests: Conflict of interestThe authors declare no competing interests., (© Indian Association of Cardiovascular-Thoracic Surgeons 2021.)

We present a low-cost, simple simulation model of major vascular injury repair for cardiothoracic trainees. This model uses commercially available orthopedic elastic bands to allow repetitive practice of the skills necessary during these rare but critical clinical scenarios. Practicing core skills in the simulation setting will help residents be better prepared when the situation arises., (Copyright © 2021 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Veno-venous extracorporeal membrane oxygenation (VV-ECMO) is a form of extracorporeal life support that provides total gas exchange (CO2 and O2) within the central venous circulation. The bicaval dual lumen cannula (DLC) is an option for patients requiring respiratory support with VV-ECMO. The catheter is inserted via the internal jugular vein into the superior and inferior vena cava, drains blood into the ECMO circuit for gas exchange, and then returns arterialized blood to the right heart for circulation. The DLC facilitates physical therapy, ambulation, and early extubation. This chapter will review the uses, advantages, and unique complications of the DLC., Competing Interests: Conflict of interestDr. Zwischenberger has the following to disclose: he receives royalties for a patent licensed to Avalon/Maquet for the Avalon Elite double lumen cannula, he is the recipient of grant funding from the NIH, he is a consultant on the Cytosorbents, Inc. Cardiac Advisory Board, and he is a partner in WZ-Biotech. Vanessa M. Bazan has nothing to disclose. Evan M. Taylor has nothing to disclose. Dr. Gunn has nothing to disclose., (© Indian Association of Cardiovascular-Thoracic Surgeons 2020.)

Objective: Minimally invasive surgery (MIS) is an integral component of General Surgery training and practice. Yet, little is known about how much autonomy General Surgery residents achieve in MIS procedures, and whether that amount is sufficient. This study aims to establish a contemporary benchmark for trainee autonomy in MIS procedures. We hypothesize that trainees achieve progressive autonomy, but fail to achieve meaningful autonomy in a substantial percentage of MIS procedures prior to graduation., Setting/participants: Fifty General Surgery residency programs in the United States, from September 1, 2015 to March 19, 2020. All Categorical General Surgery Residents and Attending Surgeons within these programs were eligible., Design: Data were collected prospectively from attending surgeons and categorical General Surgery residents. Trainee autonomy was assessed using the 4-level Zwisch scale (Show and Tell, Active Help, Passive Help, and Supervision Only) on a smartphone application (SIMPL). MIS procedures included all laparoscopic, thoracoscopic, endoscopic, and endovascular/percutaneous procedures performed by residents during the study. Primary outcomes of interest were "meaningful autonomy" rates (i.e., scores in the top 2 categories of the Zwisch scale) by postgraduate year (PGY), and "progressive autonomy" (i.e., differences in autonomy between PGYs) in MIS procedures, as rated by attending surgeons. Primary outcomes were determined with descriptive statistics, one-way analysis of variance (ANOVA) and Z-tests. Secondary analyses compared (i) progressive autonomy between common MIS procedures, and (ii) progressive autonomy in MIS vs. non-MIS procedures., Results: A total of 106,054 evaluations were performed across 50 General Surgery residency programs, of which 38,985 (37%) were for MIS procedures. Attendings performed 44,842 (42%) of all evaluations, including 16,840 (43%) of MIS evaluations, while residents performed the rest. Overall, meaningful autonomy in MIS procedures increased from 14.1% (PGY1s) to 75.9% (PGY5s), with significant (p < 0.001) increases between each PGY level. Meaningful autonomy rates were higher in the MIS vs. non-MIS group [57.2% vs. 48.0%, p < 0.001], and progressed more rapidly in MIS vs. non-MIS, (p < 0.05). The 7 most common MIS procedures accounted for 83.5% (n = 14,058) of all MIS evaluations. Among PGY5s performing these procedures, meaningful autonomy rates (%) were: laparoscopic appendectomy (95%); laparoscopic cholecystectomy (93%); diagnostic laparoscopy (87%); upper/lower endoscopy (85%); laparoscopic hernia repair (72%); laparoscopic partial colectomy (58%); and laparoscopic sleeve gastrectomy (45%)., Conclusions: US General Surgery residents receive progressive autonomy in MIS procedures, and appear to progress more rapidly in MIS versus non-MIS procedures. However, residents fail to achieve meaningful autonomy in nearly 25% of MIS cases in their final year of residency, with higher rates of meaningful autonomy only achieved in a small subset of basic MIS procedures., (Copyright © 2020. Published by Elsevier Inc.)

Background: The obesity epidemic has spread rapidly across the United States. Although overweight and obese patients have a paradoxically lower risk for postoperative morbidity and mortality, the risks associated with extreme classes of obesity (morbid obesity, super obesity, and super-super obesity) have not been described., Methods: We queried the National Surgical Quality Improvement Program database from 2012 to 2016. Of 1,815,251 surgical cases, there were 3,946 vascular cases, 237,777 emergency procedures, and 75,177 cases with missing data that were removed. The remaining 1,378,711 cases were included in this analysis. Multivariable linear and logistic regression was performed to assess the impact of body mass index on postoperative outcomes., Results: Patients within the super obesity and super-super obesity groups had the highest procedure-adjusted mortality risk among all body mass index classes (odds ratio = 2.31 and 2.63, respectively). Morbid obesity and underweight groups had moderate risk (odds ratio = 1.37 and 1.88, respectively), while those in the overweight and obesity class I and II cohorts had improved or equivocal mortality risk compared to normal body mass index class patients. Risk-adjusted and unadjusted multivariable models demonstrated that extreme obesity classes (morbid obesity, super obesity, and super-super obesity) have a graduated escalation of perioperative morbidity, infectious, and critical care complications., Conclusion: Further detailing extreme obesity-related risk beyond the obesity class III umbrella is necessary for accurate risk prediction, especially with the rising prevalence of elective nonbariatric surgery in this population. Preoperative risk assessment tools should consider subgroup risk adjustment to delineate true postoperative complication risk, facilitate patient education, and address modifiable risk factors before surgery., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Hepatocellular Carcinoma (HCC) is the third most common cause of cancer related death worldwide. Adequate treatment options for patients with advanced HCC are currently limited., Materials and Methods: We studied the anti-HCC effect of FH535 and a novel derivative Y3, on proliferation, mitochondrial function and cellular metabolism focusing on the three key substrates, glutamine, glucose, and fatty acids., Results: FH535 and Y3 disrupted mitochondrial redox control in HCC cells that resulted from uncoupling mechanisms that increased proton leakage and decreased ATP production leading to apoptosis. The uncoupling effects of the sulfonamides in HCC cells were supported by the loss of activity of the methylated analogs. The accumulation of ROS significantly contributed to cell damage after the impaired autophagic machinery. These sulfonamides, FH535 and Y3, targeted glutamine and fatty acid metabolism and caused HCC cell reprograming towards the preferential use of glucose and the glycolytic pathway., Conclusions: FH535, and Y3, demonstrated potent anti-HCC activity by targeting OXPHOS, increasing dangerous levels of ROS and reducing ATP production. These sulfonamides target glutamine and FA metabolic pathways significantly increasing the cellular dependency on glycolysis., Competing Interests: CONFLICTS OF INTEREST DSW and CL have partial ownership in a for-profit venture, Epionc, Inc., that seeks to develop small-molecule inhibitors for cancer treatment. In accord with University of Kentucky policies, DSW and CL disclosed this ownership to the University of Kentucky’s Intellectual Property Committee and to a Conflict of Interest Oversight Committee.

Acute high-risk pulmonary embolism (PE) is characterized by life-threatening hemodynamic instability that may lead to refractory cardiac arrest. Recently, extracorporeal membrane oxygenation (ECMO) has been used to provide primary cardiopulmonary support for select high-risk PE patients or before surgical embolectomy. This article reviews the growing body of literature regarding ECMO support of acute high-risk PE., (Copyright © 2020 Elsevier Inc. All rights reserved.)

The severe acute respiratory syndrome (SARS)-CoV-2 is an emerging viral pathogen responsible for the global coronavirus disease 2019 (COVID)-19 pandemic resulting in significant human morbidity and mortality. Based on preliminary clinical reports, hypoxic respiratory failure complicated by acute respiratory distress syndrome is the leading cause of death. Further, septic shock, late-onset cardiac dysfunction, and multiorgan system failure are also described as contributors to overall mortality. Although extracorporeal membrane oxygenation and other modalities of mechanical cardiopulmonary support are increasingly being utilized in the treatment of respiratory and circulatory failure refractory to conventional management, their role and efficacy as support modalities in the present pandemic are unclear. We review the rapidly changing epidemiology, pathophysiology, emerging therapy, and clinical outcomes of COVID-19; and based on these data and previous experience with artificial cardiopulmonary support strategies, particularly in the setting of infectious diseases, provide consensus recommendations from ASAIO. Of note, this is a "living document," which will be updated periodically, as additional information and understanding emerges.

Generation of plasma-free hemoglobin (pfHb) and activated complement during complex cardiac surgery contributes to end-organ dysfunction. This prospective, multicenter REFRESH I (REduction in FREe Hemoglobin) randomized controlled trial evaluated the safety and feasibility of CytoSorb hemoadsorption therapy to reduce these factors during prolonged cardiopulmonary bypass (CPB). Eligible patients underwent elective, nonemergent complex cardiac surgery with expected CPB duration ≥3 hours. Exclusions included single procedures including primary coronary artery bypass graft, single valves, transplant, and left ventricular assist device extraction. TREATMENT used 2 parallel 300 mL CytoSorb hemoadsorption cartridges in a side circuit during CPB. CONTROL was standard of care. Of 52 enrolled patients, 46 underwent surgery (Safety group, n = 23 vs Control, n = 23), and 38 were evaluated for pfHb reduction (EFFICACY group, n = 18 vs CONTROL, n = 20). Type and number of serious adverse events (44 vs 43 CONTROL) were similar, as was 30-day mortality. Transient reduction in platelets during CPB was observed in both groups, especially TREATMENT, but returned to pretreatment levels after CPB without bleeding. Peak pfHb was positively correlated with CPB length (P = 0.01) but the high variability of pfHb, due to the broad surgical procedure mix, prevented detection of changes in pfHb in the overall EFFICACY population. However, the valve replacement surgery subgroup (8 vs 10 CONTROL) had the highest peak pfHb levels, and TREATMENT demonstrated significant pfHb reductions vs CONTROL (P ≤ 0.05) in CPB ≥3 hours. In the EFFICACY group, C3a and C5a were significantly reduced by treatment throughout surgery. Intraoperative hemoadsorption with CytoSorb was safe and feasible in this randomized, controlled pilot study during complex cardiac surgery. Treatment with CytoSorb resulted in significant reductions in pfHb during valve replacement surgery and reductions in C3a and C5a in the overall EFFICACY group. Future studies will target complex cardiac surgery patients with prolonged CPB to assess hemoadsorption effect on end-organ dysfunction and outcomes., (Copyright © 2019. Published by Elsevier Inc.)

Background: Leveraging Internet technologies for academic activities can be complex and expensive, costing tens of thousands of dollars. This report describes an experience in eliminating financial barriers and realizing the potential for a new paradigm in applications for surgical education and practice., Methods: After developing multiple surgical smartphone applications (apps), the report describes the acquisition of skill sets and resources to create state-of-the-art tools. Learning these techniques is nontrivial but is attainable and clearly defined. The report then discusses the trivial costs associated with complex software development, thereby opening new doors to creative uses of technology., Results: Acquisition of coding skills for smartphones took approximately 100 hours. For a simple app without data storage, EuroSCORE (European System for Cardiac Operative Risk Evaluation), total programming time was 25 hours with no additional costs. The more complex autonomy evaluation app, Zwisch Me, was used to evaluate more than 1260 cases from 15 cardiothoracic surgery training programs between January 2016 and August 2018 by using smartphone apps for data collection and a Web dashboard for data reporting. During the first year, all enrollment and data reporting was done manually, at a cost of $124. Automating user enrollment and data reporting increased costs by roughly $240, for an annual expense of $364. Total programming time for this app was approximately 120 hours., Conclusions: Mobile software is underused in the academic surgical arena. The historically large financial barriers to adoption can be overcome by acquisition of coding skills by surgical team members. Direct physician involvement will spawn previously undreamed-of creative applications to enhance practice and education., (Copyright © 2019 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)