Undisclosed financial conflicts of interest in DSM-5-TR: cross sectional analysis.

OBJECTIVE: To assess the extent and types of financial ties to industry of panel and task force members of the American Psychiatric Association's Diagnostic and Statistical Manual of Mental Disorders, fifth edition, text revision (DSM-5-TR), published in 2022. DESIGN: Cross sectional analysis. SETTING: Open Payments database, USA. PARTICIPANTS: 92 physicians based in the US who served as members of either a panel (n=86) or task force (n=6) on the DSM-5-TR with information recorded in the Centers for Medicare and Medicaid Services Open Payments database during 2016-19. This period was chosen to include the year that development of the DSM-5-TR began and the three years preceding, a time consistent with previous research on conflicts of interest and consistent with the American Psychiatric Association's disclosure requirements for the fifth revision (DSM-5) of the manual. MAIN OUTCOME MEASURES: Type and amount of compensation the panel and task force members of DSM-5-TR received during 2016-19. RESULTS: After duplicate names had been removed, 168 individuals were identified who served as either panel or task force members of the DSM-5-TR. 92 met the inclusion criteria of being a physician who was based in the US and therefore could be included in Open Payments. Of these 92 individuals, 55 (60%) received payments from industry. Collectively, these panel members received a total of $14.2m (£11.2m; €13m). One third (33.3%) of the task force members had payments reported in Open Payments. CONCLUSIONS: Conflicts of interest among panel members of DSM-5-TR were prevalent. Because of the enormous influence of diagnostic and treatment guidelines, the standards for participation on a guideline development panel should be high. A rebuttable presumption should exist for the Diagnostic and Statistical Manual of Mental Disorders to prohibit conflicts of interest among its panel and task force members. When no independent individuals with the requisite expertise are available, individuals with associations to industry could consult to the panels, but they should not have decision making authority on revisions or the inclusion of new disorders.

Postoperative antiplatelet and/or anticoagulation use does not impact complication or reintervention rates after vein repair of arterial injury: A PROOVIT study.

INTRODUCTION: The use of antiplatelet (AP) and anticoagulation (AC) therapy after autogenous vein repair of traumatic arterial injury is controversial. The hypothesis in this study was that there is no difference in early postoperative outcomes regardless of whether AC, AP, both, or neither are used. METHODS: The American Association for the Surgery of Trauma (AAST) PROspective Observational Vascular Injury Treatment (PROOVIT) registry was queried from November, 2013, to January, 2019, for arterial injuries repaired with a vein graft. Demographics and injury characteristics were compared. Need for in-hospital reoperation was the primary outcome in this four-arm study, assessed with two ordinal logistic regression models (1. no therapy vs. AC only vs. AC and AP; 2. no therapy vs. AP only vs. AC and AP). RESULTS: 373 patients (52 no therapy, 88 AP only, 77 AC only, 156 both) from 19 centers with recorded Injury Severity Scores (ISS) were identified. Patients who received no therapy were younger than those who received AP (27.0 vs. 34.2, p = 0.02), had higher transfusion requirement (p < 0.01 between all groups) and a different distribution of anatomic injury (p < 0.01). After controlling for age, sex, ISS, platelet count, hemoglobin, pH, lactate, INR, transfusion requirement and anatomic location, there was no association with postoperative medical therapy and in-hospital operative reintervention, or any secondary outcome, including thrombosis (p = 0.67, p = 0.22). CONCLUSIONS: Neither AC nor AP alone, nor in combination, impact complication rate after arterial repair with autologous vein. These patients can be safely treated with or without antithrombotics, recognizing that this study did not demonstrate a beneficial effect.

Characterization of cerebral blood flow during open cardiac massage in swine: Effect of volume status.

Introduction: Patients in cardiac arrest treated with resuscitative thoracotomy and open cardiac massage (OCM) have high rates of mortality with poor neurological outcomes. The aim of this study is to quantitate cerebral perfusion during OCM using computed tomography perfusion (CTP) imaging in a swine model of normo- and hypovolemia. Methods: Anesthetized swine underwent instrumentation with right atrial and aortic pressure catheters. A catheter placed in the ascending aorta was used to administer iodinated contrast and CTP imaging acquired. Cerebral blood flow (CBF; ml/100 g of brain) and time to peak (TTP; s) were measured. Animals were then euthanized by exsanguination (hypovolemic group) or potassium chloride injection (normovolemic group) and subjected to a clamshell thoracotomy, aortic cross clamping, OCM, and repeated CTP. Data pertaining to peak coronary perfusion pressure (pCoPP; mmHg) were collected and % CoPP > 15 mmHg (% CoPP; s) calculated post hoc. Results: Normovolemic animals (n = 5) achieved superior pCoPP compared to the hypovolemic animals (n = 5) pCoPP (39.3 vs. 12.3, p < 0.001) and % CoPP (14.5 ± 1.9 vs. 30.9 ± 6.5, p < 0.001). CTP acquisition was successful and TTP elongated from spontaneous circulation, normovolemia to hypovolemia (5.7 vs. 10.8 vs. 14.8, p = 0.01). CBF during OCM was similar between hypovolemic and normovolemic groups (7.5 ± 8.1 vs. 4.9 ± 6.0, p = 0.73) which was significantly lower than baseline values (51.9 ± 12.1, p < 0.001). Conclusion: OCM in normovolemia generates superior coronary hemodynamics compared to hypovolemia. Despite this, neither generates adequate CBF as measured by CTP, compared to baseline. To improve the rate of neurologically intact survivors, novel resuscitative techniques need to be investigated that specifically target cerebral perfusion as existing techniques are inadequate.

A swine model of reproducible timed induction of peripheral arterial shunt failure: Developing warning signs of imminent shunt failure.

Temporary intravascular shunts are used to maintain perfusion in injured vessels, although failure can be unpredictable and lead to significant morbidity. The aim of the present study was to develop a dose- and timing-controlled swine model of intrinsic shunt failure to facilitate the development of a warning system for impending failure. Ten Yorkshire swine (weight, 56.6 ± 4.2 kg) underwent bilateral Argyle shunt (Cardinal Health, Dublin, OH) placement in the external iliac arteries, with proximal cannulation of the circumflex iliac arteries for infusion of thrombin. The thrombin infusion was randomized to the left or right side for 5000 vs 10,000 U/h. The 5000-U/h group required 2.1 times as long as the 10,000-U/h group to reach failure (mean, 21.8 minutes vs 46.4 minutes; P < .0001), as shown by a Kaplan-Meier survival analysis (log-rank P < .0001). However, the 5000-U/h group required the same total amount of thrombin (mean, 3752 ± 856 U; P = .57). Thus, time- and/or thrombin dose-controlled induction of shunt failure is technically feasible. Furthermore, in the final 15 minutes before failure, the flow was similar between the two groups (P > .05), and the slope of the flow curve became more negative the closer the model was to failure. Overall, this model could be used to develop an alert system to predict for impending shunt failure or the need for intervention.

Whole Blood Selective Aortic Arch Perfusion for Exsanguination Cardiac Arrest: Assessing Myocardial Tolerance to the Duration of Cardiac Arrest.

INTRODUCTION: Selective aortic arch perfusion (SAAP) is an endovascular technique that consists of aortic occlusion with perfusion of the coronary and cerebral circulation. It been shown to facilitate return of spontaneous circulation (ROSC) after exanguination cardiac arrest (ECA), but it is not known how long arrest may last before the myocardium can no longer be durably recovered. The aim of this study is to assess the myocardial tolerance to exsanguination cardiac arrest before successful ROSC with SAAP. METHODS: Male adult swine (n = 24) were anesthetized, instrumented, and hemorrhaged to arrest. Animals were randomized into three groups: 5, 10, and 15 min of cardiac arrest before resuscitation with SAAP. Following ROSC, animals were observed for 60 min in a critical care environment. Primary outcomes were ROSC, and survival at 1-h post-ROSC. RESULTS: Shorter cardiac arrest time was associated with higher ROSC rate and better 1-h survival. ROSC was obtained for 100% (8/8) of the 5-min ECA group, 75% (6/8) of the 10-min group, 43% (3/7) of the 15-min group (P = 0.04). One-hour post-ROSC survival was 75%, 50%, and 14% in 5-, 10-, and 15-min groups, respectively (P = 0.02). One-hour survivors in the 5-min group required less norepinephrine (1.31 mg ±â€Š0.83 mg) compared with 10-SAAP (0.76 mg ±â€Š0.24 mg), P = 0.008. CONCLUSION: Whole blood SAAP can accomplish ROSC at high rates even after 10 min of unsupported cardiac arrest secondary to hemorrhage, with some viability beyond to 15 min. This is promising as a tool for ECA, but requires additional optimization and clinical trials.Animal Use Protocol, IACUC: 0919015.

The Underlying Cardiovascular Mechanisms of Resuscitation and Injury of REBOA and Partial REBOA.

Introduction: Resuscitative Endovascular Balloon Occlusion of the Aorta (REBOA) is used for aortic control in hemorrhagic shock despite little quantification of its mechanism of resuscitation or cardiac injury. The goal of this study was to use pressure-volume (PV) loop analysis and direct coronary blood flow measurements to describe the physiologic changes associated with the clinical use of REBOA. Methods: Swine underwent surgical and vascular access to measure left ventricular PV loops and left coronary flow in hemorrhagic shock and subsequent placement of occlusive REBOA, partial REBOA, and no REBOA. PV loop characteristics and coronary flow are compared graphically with PV loops and coronary waveforms, and quantitatively with measures of the end systolic and end pressure volume relationship, and coronary flow parameters, with accounting for multiple comparisons. Results: Hemorrhagic shock was induced in five male swine (mean 53.6 ± 3.6 kg) as demonstrated by reduction of stroke work (baseline: 3.1 vs. shock: 1.2 L*mmHg, p < 0.01) and end systolic pressure (ESP; 109.8 vs. 59.6 mmHg, p < 0.01). ESP increased with full REBOA (178.4 mmHg; p < 0.01), but only moderately with partial REBOA (103.0 mmHg, p < 0.01 compared to shock). End systolic elastance was augmented from baseline to shock (1.01 vs. 0.39 ml/mmHg, p < 0.01) as well as shock compared to REBOA (4.50 ml/mmHg, p < 0.01) and partial REBOA (3.22 ml/mmHg, p = 0.01). Percent time in antegrade coronary flow decreased in shock (94%-71.8%, p < 0.01) but was rescued with REBOA. Peak flow increased with REBOA (271 vs. shock: 93 ml/min, p < 0.01) as did total flow (peak: 2136, baseline: 424 ml/min, p < 0.01). REBOA did not augment the end diastolic pressure volume relationship. Conclusion: REBOA increases afterload to facilitate resuscitation, but the penalty is supraphysiologic coronary flows and imposed increase in LV contractility to maintain cardiac output. Partial REBOA balances the increased afterload with improved aortic system compliance to prevent injury.

A technical and data analytic approach to pressure-volume loops over numerous cardiac cycles.

Cardiac pressure-volume (PV) loop analysis is the reference standard for studying the cardiovascular implications of clinical perturbations (eg, heart failure, aortic occlusion, hypovolemia) and is a benchmark for comparisons with noninvasive alternatives (eg, ultrasound, magnetic resonance imaging). Historically, most PV loop analyses were of individual cardiac cycles for which the options to analyze PV loops using off-the-shelf software were limited, and home-grown analysis software often lacked peer review or code-sharing. Our aim was to describe a start-to-finish implementation of PV loops for determination of hemodynamic parameters in swine, to provide technical advice for vascular access and proceduralization, and to describe data capture, curation, preprocessing, and analysis of raw PV time data. We have provided a novel data analytic method to programmatically analyze raw PV loop data beyond single cardiac cycles and real, raw swine PV loop data and the accompanying MATLAB (MathWorks, Inc, Natick, Mass) code as an example of how to process and analyze raw data directly.

In-hospital outcomes in autogenous vein versus synthetic graft interposition for traumatic arterial injury: A propensity-matched cohort from PROOVIT.

BACKGROUND: The ideal conduit for traumatic arterial repair is controversial. Autologous vein was compared with synthetic interposition grafts in the acute setting. The primary outcome was in-hospital reoperation or endovascular intervention. METHODS: The American Association for the Surgery of Trauma PROspective Observational Vascular Injury Treatment registry from November 2013 to January 2019 was queried for arterial injuries requiring interposition vein or graft repair. Patients with no recorded Injury Severity Score were excluded, and multiple imputation was used for other missing data. Patients treated with synthetic grafts (SGs) were propensity matched to patients with vein grafts (VGs) to account for preoperative differences. RESULTS: Four hundred sixty from 19 institutions were identified, with 402 undergoing VG and 58 SG. In the SG group, 45 were PTFE grafts, 5 were Dacron, and 8 had other conduits. The SG group was more severely injured at admission with more gunshot wounds and higher mean Injury Severity Score, lactate, and first-24-hour transfusion requirement. In addition, the SG cohort had significantly lower admission systolic blood pressure, pH, and hemoglobin. After propensity matching, 51 patients with SG were matched with 87 patients with VG. There were no differences in demographics, clinical parameters, or diagnostic evaluation techniques postmatch. The need for reoperation or endovascular intervention between the matched groups was equivalent (18%; p = 0.8). There was no difference in any secondary outcome including thrombosis, stenosis, pseudoaneurysm, infection, or embolic event, and hospital and intensive care unit length of stay were the same. CONCLUSION: American Association for the Surgery of Trauma PROspective Observational Vascular Injury Treatment registry data demonstrate that SGs are used in more critically ill patients. After controlling for relevant clinical factors and propensity matching, there is no in-hospital difference in rate of reoperation or endovascular intervention, or any secondary outcome between VG and SG. LEVEL OF EVIDENCE: Prognostic and Epidemiolgic, Level III.

Class of hemorrhagic shock is associated with progressive diastolic coronary flow reversal and diminished left ventricular function.

Introduction: The relationship between coronary artery flow and left ventricular (LV) function during hemorrhagic shock remains unknown. The aim of this study was to quantify coronary artery flow directionality alongside left ventricular function through the four classes of hemorrhage shock. Methods: Following baseline data collection, swine were exsanguinated into cardiac arrest via the femoral artery using a logarithmic bleed, taking each animal through the four classes of hemorrhagic shock based on percent bleed (class I: 15%; class II: 15%-30%; class III: 30%-40%; class IV: >40%). Telemetry data, left ventricular pressure-volume loops, and left anterior descending artery flow tracings over numerous cardiac cycles were collected and analyzed for each animal throughout. Results: Five male swine (mean 72 ± 12 kg) were successfully exsanguinated into cardiac arrest. Mean left ventricular end-diastolic volume, end-diastolic pressure, and stroke work decreased as the hemorrhagic shock class progressed (p < 0.001). The proportion of diastole spent with retrograde coronary flow was also associated with class of hemorrhagic shock (mean 5.6% of diastole in baseline, to 63.9% of diastole in class IV; p < 0.0001), worsening at each class from baseline through class IV. Preload recruitable stroke work (PRSW) decreased significantly in classes II through IV (p < 0.001). Systemic Vascular Resistance (SVR) is associated with class of hemorrhage shock (p < 0.001). Conclusion: With progressive classes of hemorrhagic shock left ventricular function progressively decreased, and the coronary arteries spent a greater proportion of diastole in retrograde flow, with progressively more negative total coronary flow. Preload recruitable stroke work, a load-independent measure of inotropy, also worsened in severe hemorrhagic shock, indicating the mechanism extends beyond the drop in preload and afterload alone.

Postoperative complications of endovascular blunt thoracic aortic injury repair.

BACKGROUND: Thoracic endovascular aortic repair (TEVAR) has become the standard of care for thoracic aortic aneurysms and increasingly for blunt thoracic aortic injury (BTAI). Postoperative complications, including spinal cord ischemia and paraplegia, have been shown to be less common with elective TEVAR than with open thoracic or thoracoabdominal repair. Although small cohort studies exist, the postoperative complications of endovascular repair of traumatic aortic injury have not been described through large data set analysis. METHODS: A retrospective cohort analysis was performed of the American College of Surgeons Trauma Quality Improvement Program registry spanning from 2007 to 2017. All patients with BTAI who underwent TEVAR, as indicated by the Abbreviated Injury Scale or the International Classification of Diseases (ICD-9 or ICD-10), were included. Categorical data were presented as proportions and continuous data as mean and SD. OR was calculated for each postoperative complication. RESULTS: 2990 patients were identified as having undergone TEVAR for BTAI. The postoperative incidence of stroke was 2.8% (83), and 4.7% (140) of patients suffered acute kidney injury or renal failure. The incidence of spinal cord ischemia was 1.9% (58), whereas 0.2% (7) of patients suffered complete paraplegia. Renal events and stroke were found to occur significantly more frequently in those undergoing TEVAR (OR 1.758, 1.449-2.134 and OR 2.489, 1.917-3.232, respectively). Notably, there was no difference between TEVAR and non-operative BTAI incidences of spinal cord ischemia or paraplegia (OR 1.061, 0.799-1.409 and OR 1.698, 0.728-3.961, respectively). DISCUSSION: Postoperative intensive care unit care of patients after BTAI has historically focused on awareness of spinal cord ischemia. Our analysis suggests that after endovascular repair of blunt aortic trauma, care should involve vigilance primarily against postoperative cerebrovascular and renal events. Further study is warranted to develop guidelines for the intensivist managing patients after TEVAR for BTAI. LEVEL OF EVIDENCE: Level III.

Measuring Cardiac Output in a Swine Model.

Swine are frequently used in medical research given their similar cardiac physiology to that of humans. Measuring cardiac parameters such as stroke volume and cardiac output are essential in this type of research. Contrast ventriculography, thermodilution, and pressure-volume loop (PV-loop) catheters can be used to accurately obtain cardiac performance data depending on which resources and expertise are available. For this study,five Yorkshire swine were anesthetized and intubated. Central venous and arterial access was obtained to place the necessary measurement instruments.A temperature probe was placed in the aortic root. A cold saline bolus was delivered to the right atrium and temperature deflection curve was recorded. Integration of the area under the curve allowed for the calculation of the current cardiac output.A pigtail catheter was percutaneously placed in the left ventricle and 30 mL of iodinated contrast was power injected over 2 seconds. Digital subtraction angiography images were uploaded to volumetric analysis software to calculate the stroke volume and cardiac output. A pressure volume-loop catheter was placed into the left ventricle (LV) and provided continuous pressure and volume data of the LV, which allowed the calculation of both stroke volume and cardiac output.All three methods demonstrated good correlation with each other. The PV-loop catheter and thermodilution exhibited the best correlation with a 3% error and a Pearson coefficient of 0.99, with 95% CI=0.97 to 1.1, (p=0.002). The PV-loop catheter against ventriculography also showed good correlation with a 6% error and a Pearson coefficient of 0.95, 95% CI=0.96 to 1.1 (p=0.01). Finally, thermodilution against ventriculography had a 2% error with r=0.95, 95% CI=0.93 to 1.11, (p=0.01). In conclusion, we state that the PV-loop catheter, contrast ventriculography, and thermodilution each offer certain advantages depending on the researcher's requirements. Each method is reliable and accurate for measuring various cardiac parameters in swine such as the stroke volume and cardiac output.

The Cardiac Physiology Underpinning Exsanguination Cardiac Arrest: Targets for Endovascular Resuscitation.

ABSTRACT: Exsanguination leading to cardiac arrest is the terminal phase of uncontrolled hemorrhage. Resuscitative interventions have focused on preload and afterload support. Outcomes remain poor due to several factors but poor coronary perfusion undoubtedly plays a role. The aim of this study is to characterize the relationship between arterial pressure and flow during hemorrhage in an effort to better describe the terminal phases of exsanguination.Male swine weighing 60 kg to 80 kg underwent splenectomy and instrumentation followed by a logarithmic exsanguination until asystole. Changes in hemodynamic parameters over time were compared using one-way, repeated measures analysis of variance.Nine animals weighing 69 ±â€Š15 kg were studied. Asystole occurred at 53 ±â€Š13 min when 52 ±â€Š11% of total blood volume has been shed. The greatest fall in mean hemodynamic indices were noted in the first 15 min: SBP (80-42 mm Hg, P = 0.02), left ventricular end-diastolic volume (94-52 mL, P = 0.04), cardiac output (4.8-2.4 L/min, P = 0.03), coronary perfusion pressure (57-30 mm Hg, P = 0.01), and stroke volume (60-25 mL, P = 0.02). This corresponds to the greatest rate of exsanguination. Organized cardiac activity was observed until asystole without arrythmias. Coronary flow was relatively preserved throughout the study, with a precipitous decline once mean arterial pressure was less than 20 mm Hg, leading to asystole.In this model, initial hemodynamic instability was due to preload failure, with asystole occurring relatively late, secondary to failure of coronary perfusion. Future resuscitative therapies need to directly address coronary perfusion failure if effective attempts are to be made to salvage these patients.

Development of a Selective Aortic Arch Perfusion System in a Porcine Model of Exsanguination Cardiac Arrest.

Hemorrhage constitutes the majority of potentially preventable deaths from trauma. There is growing interest in endovascular resuscitation techniques such as selective aortic arch perfusion (SAAP) for patients in cardiac arrest. This involves active perfusion of the coronary circulation via a thoracic aortic balloon catheter and is approaching clinical application. However, the technique is complex and requires refinement in animal models before human use can be considered. This paper describes a large animal model of exsanguination cardiac arrest treated with a bespoke SAAP system. Swine were anesthetized, instrumented and a splenectomy was performed before a controlled, logarithmic exsanguination was initiated. Animals were heparinized and the shed blood collected in a reservoir. Once cardiac arrest was observed, the blood was pumped through an extra-corporeal circuit into an oxygenator and then delivered through a 10 Fr balloon catheter placed in the thoracic aorta. This resulted in the return of a spontaneous circulation (ROSC) as demonstrated by ECG and aortic root pressure waveform. This model and accompanying SAAP system allow for standardized and reproducible recovery from exsanguination cardiac arrest.

Radial versus femoral arterial access for trauma endovascular interventions: A noninferiority study.

BACKGROUND: The majority of endovascular interventions for trauma are performed using transfemoral access (TFA). Transradial access (TRA) is a recently integrated alternative at the authors' institution. This noninferiority study compares the technical success and complication rate of TRA compared with TFA. METHODS: All patients undergoing emergent endovascular interventions between March 2016 and March 2019 were identified from a prospectively maintained database. Data were collected on access type, complications, and procedural success. A noninferiority margin was established from previous randomized trials for technical success (0.475) and complications (0.015). RESULTS: Over 3 years, 96 patients underwent TRA and 335 patients received TFA. The overall technical success rate was 98.1%, without significance based on access strategy (p = 0.078). All femoral arteries and 97.9% (n = 94) of radial arteries were accessed as intended. Complications occurred in 1.0% of TRA and 9.9% of TFA groups (p = 0.002). In the TFA group, complications included access site bleeding, hematoma, pseudoaneurysm, lower limb ischemia, and femoral artery thrombosis (n = 6, 14, 3, 3, and 4, respectively). In the TRA group, complications included radial artery thrombosis (n = 1). Transradial access procedural success and complication rate fell within the lower bound confidence interval of the noninferiority margin, demonstrated the noninferiority of TRA in this data set. CONCLUSION: Transradial access in a cohort of trauma patients undergoing endovascular intervention does not appear to be inferior to TFA in relation to technical success and complications. For patients where groin access may be challenging, TRA is a useful, efficacious, and safe alternative. Longer-term study is required to fully characterize the advantages and disadvantages of TRA compared with TFA. LEVEL OF EVIDENCE: Therapeutic V.