Changes in Pulmonary Vascular Resistance and Obstruction Score Following Acute Pulmonary Embolism in Pigs.

OBJECTIVES: To investigate the contribution of mechanical obstruction and pulmonary vasoconstriction to pulmonary vascular resistance (PVR) in acute pulmonary embolism (PE) in pigs. DESIGN: Controlled, animal study. SETTING: Tertiary university hospital, animal research laboratory. SUBJECTS: Female Danish slaughter pigs (n = 12, ~60 kg). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: PE was induced by infusion of autologous blood clots in pigs. CT pulmonary angiograms were performed at baseline, after PE (first experimental day [PEd0]) and the following 2 days (second experimental day [PEd1] and third experimental day [PEd2]), and clot burden quantified by a modified Qanadli Obstruction Score. Hemodynamics were evaluated with left and right heart catheterization and systemic invasive pressures each day before, under, and after treatment with the pulmonary vasodilators sildenafil (0.1 mg/kg) and oxygen (Fio2 40%). PE increased PVR (baseline vs. PEd0: 178 ± 54 vs. 526 ± 160 dynes; p < 0.0001) and obstruction score (baseline vs. PEd0: 0% vs. 45% ± 13%; p < 0.0001). PVR decreased toward baseline at day 1 (baseline vs. PEd1: 178 ± 54 vs. 219 ± 48; p = 0.16) and day 2 (baseline vs. PEd2: 178 ± 54 vs. 201 ± 50; p = 0.51). Obstruction score decreased only slightly at day 1 (PEd0 vs. PEd1: 45% ± 12% vs. 43% ± 14%; p = 0.04) and remained elevated throughout the study (PEd1 vs. PEd2: 43% ± 14% vs. 42% ± 17%; p = 0.74). Sildenafil and oxygen in combination decreased PVR at day 0 (-284 ± 154 dynes; p = 0.0064) but had no effects at day 1 (-8 ± 27 dynes; p = 0.4827) or day 2 (-18 ± 32 dynes; p = 0.0923). CONCLUSIONS: Pulmonary vasoconstriction, and not mechanical obstruction, was the predominant cause of increased PVR in acute PE in pigs. PVR rapidly declined over the first 2 days after onset despite a persistent mechanical obstruction of the pulmonary circulation from emboli. The findings suggest that treatment with pulmonary vasodilators might only be effective in the acute phase of PE thereby limiting the window for such therapy.

Dexamethasone Is Associated With a Statistically Significant Increase in Postoperative Blood Glucose Levels Following Primary Total Knee Arthroplasty.

Background: Dexamethasone has the potential to cause a transient increase in blood glucose levels. Recent evidence has suggested the potential for a linearly increased risk of periprosthetic joint infection beginning at blood glucose levels of ≥115 mg/dL and an optimal cutoff of 137 mg/dL. We designed the following study to determine (1) what percentage of our patients had postoperative day 1 (POD1) glucose levels above 137 mg/dL and (2) if the administration of dexamethasone further increased this risk. Methods: All primary total knee arthroplasties performed from 1998 to 2021 at our institution were identified and retrospectively reviewed. Patient demographics, dexamethasone administration, and perioperative glucose levels were recorded. Outcomes included POD1 glucose levels, infection rate, and all-cause reoperations and revisions. Results: The average POD1 glucose level for the entire cohort (n = 5353) was 138.7 mg/dL. The percentage of patients with a glucose level of 137 mg/dL or higher was significantly greater in patients that received dexamethasone (55.2% vs 37.7%; P < .0001). Significantly higher glucose levels were seen with dexamethasone administration in both diabetic (187.7 vs 173.4 mg/dL; P < .0001) and nondiabetic patients (137.7 vs 128.0 mg/dL; P < .0001). Dexamethasone use was associated with a nonstatistically significant increase in infection rates (1.7% vs 1.0%; P = .177). Conclusions: Administration of dexamethasone is associated with a statistically significant increase in POD1 glucose levels, regardless of diabetic status. Dexamethasone use should continue to be closely monitored given the potential risks of elevated postoperative glucose levels and the potential for periprosthetic infection.

Impact of the COVID-19 Pandemic on Pediatric Elbow Fractures: Marked Change in Management and Resource Utilization, Without a Change in Incidence.

BACKGROUND: Elbow fractures are the most common pediatric fractures requiring operative treatment. Although recent reports have suggested that the COVID-19 pandemic has markedly reduced the incidence of pediatric fractures, no study has specifically evaluated the impact on pediatric elbow fractures. This study aimed to evaluate changes in the incidence, severity, and resource utilization for managing pediatric elbow fractures during the COVID-19 pandemic, compared with prepandemic years. METHODS: A prepandemic (2007 to 2017) cohort and a COVID-19 pandemic period (March 2020 to March 2021) cohort of pediatric elbow injuries from a single tertiary hospital were retrospectively examined and compared. Exclusion criteria included outside treatment or lack of diagnosis by an orthopedist. Presentation information, injury patterns, transport, and treatment requirements were collected. RESULTS: Although the incidence of pediatric elbow fractures and rate of neurovascular injury were comparable, seasonal patterns were not sustained and the rate of fracture displacement was found to be significantly elevated in the COVID-19 period compared with nonpandemic years. Likewise, marked changes to where patients first presented (emergency department vs. Clinic), how the patients were transported, and the distance traveled for care were observed. Specifically, patients were more likely to present to the clinic, were more likely to self-transport instead of using emergency medical service transportation, and traveled a greater distance for care, on average. Aligning with these changes, the resources utilized for the treatment of pediatric elbow fracture markedly changed during the COVID-19 period. This study found that there was an increase in the overall number of surgeries performed, the total operative time required to treat elbow fractures, and the number of patients requiring admission during the COVID-19 period. CONCLUSIONS: These data provide a contrasting viewpoint to prior reports, illustrating that the incidence of elbow fractures remained consistent during the COVID-19 period, whereas the operative volume and need for hospital admission increased compared with years prior. Furthermore, this study demonstrated how the COVID-19 pandemic altered the interface between pediatric patients with elbow fractures and our institution regarding the location of presentation and transportation. LEVEL OF EVIDENCE: Level III-retrospective cohort study.

Location of Initial Closed Reduction Attempt Significantly Increases Cost and Length of Stay in Total Hip Arthroplasty.

Background: Prosthetic hip dislocation remains one of the most frequent complications following total hip replacement. Dislocations are predominantly managed by a closed reduction in the emergency department (ED) or the operating room (OR). This study aimed to evaluate how the location of an initial closed reduction attempt impacts a patient's course of care including length of stay (LOS) and cost of care. Material and methods: A retrospective chart review was performed on all patients presenting to a single ED with a unilateral prosthetic hip dislocation from 2009 to 2019. A total of 108 patients were identified. Data collected included patient demographics, ED/hospital course, and hospital charges. Results: Seventy-four patients (69%) had initial reduction attempted in the ED (65/74, 88% were successful), while 34 patients (31%) went directly to OR (100% successful with closed reduction). Failed closed reduction in ED or direct to OR resulted in a greater LOS and rate of placement to a skilled nursing facility following discharge. Median hospital charges for successful ED reduction were $6,837, while failed ED closed reduction or direct to OR resulted in median charges of $27,317 and $20,481, respectively. Conclusion: Many patients successfully underwent closed reduction in the ED, and there was no difference in complications, independent of where the reduction was first performed. Patients undergoing reduction in the OR had greater LOS and cost of care, independent of whether a reduction attempt was performed and failed in the ED, than those successfully reduced in the ED.

Predicting Mortality in Elderly Spine Trauma Patients.

STUDY DESIGN: Retrospective analysis on prospectively collected data. OBJECTIVE: The aim of this study was to construct a clinical prediction model for 90-day mortality in elderly patients with traumatic spine injuries. SUMMARY OF BACKGROUND DATA: Spine trauma in the elderly population is increasing. Comparing elderly spine trauma patients to younger patients with similar injuries proves challenging due to the extensive comorbidities and frailty found in the elderly. There is a paucity of evidence to predict survival of elderly patients following traumatic spinal injuries. METHODS: All patients 65+ with spine trauma presenting to a level I trauma center from 2010 to 2019 were reviewed from a prospectively maintained trauma registry. Retrospective chart review was performed to record injury, frailty scores, comorbidities, presence of spinal cord injury, imaging evidence of sarcopenia and osteopenia, mortality, and complications. We preselected 13 variables for our multivariable logistic regression model: hypotension on admission, gender, marital status, age, max Abbreviated Injury Scale, Modified Frailty Index, surgical treatment, hematocrit, white blood count, spinal cord injury, closed head injury, injury level and presence of high energy mechanism. The performance of the prediction model was evaluated using a concordance index and calibration plot. The model was internally validated via bootstrap approach. RESULTS: Over the 9-year period, 1746 patients met inclusion criteria; 359 (20.6%) patients died within 90 days after presenting with spine trauma. The most important predictors for 90-day mortality were age, hypotension, closed head injury, max Abbreviated Injury Scale and hematocrit. There was an optimism-corrected C-index of 0.77. A calculator was created to predict a personalized mortality risk. CONCLUSION: The incidence of spine trauma in elderly patients continues to increase. Previous publications described preexisting conditions that imply increased mortality, but ours is the first to develop a predictive calculator. Prospective research is planned to externally validate this model to better determine its predictive value and utility in the clinical setting.

Nonaccidental Trauma in Pediatric Elbow Fractures: When You Should Be Worried.

BACKGROUND: Nonaccidental trauma (NAT) is a rising source of morbidity and mortality in the pediatric population. Fractures are often the first cause for presentation to health care providers in the case of NAT but can be misidentified as accidental. Given that elbow fractures are the most common accidental injuries among pediatric patients, they are not traditionally associated with NAT. This study aims to determine the prevalence of NAT among elbow fractures and identify common features in nonaccidental elbow fractures. METHODS: Current Procedural Terminology (CPT) codes were used to retrospectively identify all pediatric (0 to 17) elbow fractures at a single, tertiary children's hospital between 2007 and 2017. Among these, all fractures for which an institutional child abuse evaluation team was consulted were identified. The medical record was then used to determine which of these fractures were due to NAT. Standard injury radiographs of all victims of NAT as well as all patients under 1 year of age were blinded and radiographically evaluated for fracture type by a pediatric orthopaedic surgeon. RESULTS: The prevalence of nonaccidental elbow fractures across the 10-year study period was 0.4% (N=18). However, the prevalence of nonaccidental elbow fractures in those patients below 1 year of age was markedly higher at 30.3% (10/33). Among all elbow fractures in patients below 1 year of age, supracondylar humerus fractures were the most common fracture type (19/33, 57.6%), yet transphyseal fractures (6/33, 18.1%) were most commonly the result of NAT (5/6, 83.3%). In children over 1 year of age, fracture type was not an indicator of NAT. CONCLUSIONS: The vast majority of pediatric elbow fractures (99.6%) are accidental. However, certain factors, namely age below 1 year and transphyseal fractures increase the likelihood that these fractures may be a result of NAT. LEVEL OF EVIDENCE: Level IV: retrospective case series.

Bruise Location in Supracondylar Humerus Fractures Predicts Specific Neurovascular Injuries.

PURPOSE: The presence of soft tissue injury in pediatric supracondylar humerus fractures (SCHFs) has been shown to be an independent predictor of any neurovascular injury. Potentially expanding this concept, the specific neurovascular structure injured around the elbow is thought to be dependent upon the direction and magnitude of fracture displacement and subsequent soft tissue injury. Therefore, it was hypothesized that the bruise location following SCHF is indicative of the anatomic location of maximal soft tissue injury and therefore is a specific prognosticator of which neurovascular structure may be injured. METHODS: Retrospective chart review of all SCHFs treated at a tertiary pediatric hospital from 2007 to 2017 collected information on bruise location, neurovascular injury patterns, and outcomes. Bruise location was classified as anterior, anterolateral, anteromedial, or posterior. Injury radiographs were reviewed by a blinded pediatric orthopaedic surgeon to neurovascular structure injured. RESULTS: Of 2845 SCHFs identified, 267 (9.4%) had concomitant neurovascular injury-of which 128 (47.9%) met inclusion criteria. Among the vascular injuries, all bruising was anteromedial (28/45, 62.2%, P<0.05) or anterior (17/45, 37.8%, P>0.05). Fractures with anteromedial bruising correlated with median nerve injury (24/27, 88.9%, P<0.05), whereas fractures with anterolateral bruising correlated with radial nerve injuries (24/25, 96.0%, P<0.05). Bruising or radiographic evaluation correctly identified 60.2% and 64.1% of neurovascular injuries, respectively, whereas the combination identified 82.0% of neurovascular injuries correctly. Bruise location identified 23 neurovascular injuries not predicted by radiographic evaluation alone. CONCLUSION: Bruise location is an important physical examination finding that can be used as an adjunct to improve the diagnostic accuracy of neurovascular injury in SCHFs in conjunction with neurovascular physical examination and radiographic evaluation. SCHFs with anterior or anteromedial bruising should raise concern for vascular injury. In addition, anteromedial bruising is predictive of a median nerve injury and anterolateral bruising is predictive of radial nerve injury. This adjunct diagnostic is particularly helpful in a noncooperative child or if performed by a clinician with limited experience in diagnosing neurovascular injuries or interpreting pediatric elbow radiographs. LEVEL OF EVIDENCE: Level IV, case series.

A Mini-Open Approach to Medial Pinning in Pediatric Supracondylar Humeral Fractures May Be Safer Than Previously Thought.

BACKGROUND: Displaced pediatric supracondylar humeral fractures (SCHFs) are stabilized after reduction by smooth pins. Although some SCHFs are biomechanically stable after lateral-only entry pinning (lateral pinning), an additional medial entry pin (cross-pinning) confers superior stabilization in some SCHFs. There is a recognized risk of iatrogenic ulnar nerve injury with medial entry pinning. The best existing evidence has estimated an iatrogenic ulnar nerve injury rate of approximately 3.4% in cross-pinning. In similar studies, the rate of iatrogenic nerve injury (all nerves) in lateral pinning is estimated at 1.9%. This study aimed to use a large, single-center, single-technique (mini-open) retrospective case series to determine the rate of iatrogenic ulnar nerve injury in cross-pinning. METHODS: Patients undergoing percutaneous cross-pinning via the mini-open technique for SCHFs from 2007 to 2017 were retrospectively reviewed. Injury characteristics, operative variables, fixation technique, and complications, such as iatrogenic nerve injury, were recorded. Patients who underwent operative treatment at another hospital, had no postoperative follow-up, or died due to polytrauma were excluded. RESULTS: In this study, 698 patients undergoing cross-pinning during the study period were identified. Patients treated with cross-pinning had severe fractures, including a total of 198 preoperative neurovascular injuries (28.4%), 32 patients (4.6%) with skin tenting, and 19 patients (2.7%) with open fractures. Iatrogenic nerve injury was reported in 3 cases (0.43%), all of which affected the ulnar nerve. In 2 of 3 cases of iatrogenic nerve injury, the ulnar nerve symptoms resolved at a mean follow-up of 15 weeks. CONCLUSIONS: The mini-open approach for medial pin insertion is safer than previous estimates. Here, in the largest single-center study of cross-pinning for SCHFs, the iatrogenic ulnar nerve injury rate of 0.43% was nearly 10 times lower than estimated rates from recent meta-analyses. Considering all nerves, the iatrogenic injury rate for this cross-pinning cohort was also lower than the estimated iatrogenic nerve injury rate for lateral pinning. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Predicting factors for pulmonary embolism response team activation in a general pulmonary embolism population.

Pulmonary embolism response teams (PERT) aim to improve treatment of acute pulmonary embolism (PE). PERT focus on intermediate- and high-risk PE patients, but recent multicenter studies show that low-risk PE patients compose one in five of all PERT cases. Conversely, not all intermediate- and high-risk PE patients elicit a PERT activation. The factors leading to PERT activations remain unknown. This study aims to describe the patient characteristics associated with PERT activation for low-risk PE patients and characteristics precluding PERT activation for intermediate/high-risk PE patients. We analysed data from all patients with confirmed PE diagnosed in the Massachusetts General Hospital Emergency Department from August 2013 to February 2017 and cross-referred these data with patients who received a PERT activation and patients who did not. Patients were stratified into low-risk or intermediate/high-risk PE. Univariate analyses were performed within each risk group comparing patients with a PERT activation and patients without. Fifteen percent (56/374) of low-risk PE patients triggered a PERT activation. Patient characteristics associated with PERT activation were: (1) vascular disease, (2) pulmonary diseases, (3) thrombophilia, (4) current use of anticoagulants, (5) central PE and (6) concurrent DVT. Thirty-five percent (110/283) of intermediate/high-risk PE patients did not elicit a PERT activation. Patient characteristics precluding a PERT activation were: (1) vascular disease, (2) malignancies and (3) asymptomatic presentation. Low-risk PE patients with PERT activations had more extensive clot burden, complex comorbidities, or had failed anticoagulation treatment. Intermediate/high-risk PE patients without PERT activations tended to have malignancies or vascular disease.

A Virtual Wellness and Learning Communities Program for Medical Students during the COVID-19 Pandemic.

OBJECTIVES: Numerous studies have demonstrated the high risk for burnout and mental illness in medical students. Because of the coronavirus disease 2019 (COVID-19) pandemic, our medical school transitioned to an all-virtual learning environment from March to June 2020, which raised concerns among student leaders and administrators, as reduced interpersonal attachments have known associations with decreased mental health. In an effort to facilitate student well-being during the pandemic, the Virtual Wellness and Learning Communities (VWLC) program was established. VWLC consisted of hour-long events that offered students the opportunity to engage with their peers online. METHODS: More than 20 events and workshops were conducted from March to June 2020, including trivia nights, song and guitar performances, sketching, video editing tutorials, chess lessons, yoga, and personal investing tips. An institutional review board-approved survey to assess the efficacy of the VWLC program was sent to medical student participants and nonparticipants. RESULTS: The overall response rate of this study was 43% (53/123). The response rate for students who attended a VWLC event was 51% (33/65), and the response rate for students who did not attend a VWLC event was 34% (20/58). Of all of the respondents, 85% (45/53) reported a decreased sense of connectivity with peers because of the pandemic, and 40% (21/53) reported a decrease in their sense of wellness. After attending a VWLC event, 79% (26/33) reported an increased sense of peer connectivity, 61% (20/33) reported improved wellness, and 55% (18/33) believed that these events should continue postpandemic to supplement in-person programming. Those who did not attend a virtual event stated that the main barriers to attending were unfamiliarity with attendees and screen fatigue. CONCLUSIONS: The COVID-19 pandemic has worsened medical student well-being and sense of community. VWLC programming may be an effective strategy for promoting medical student wellness and community while social distancing during the COVID-19 pandemic. To our knowledge, this is the first virtual wellness program for promotion of medical student mental health during the COVID-19 pandemic to be described in the literature.

Putative Biomarkers for Acute Pulmonary Embolism in Exhaled Breath Condensate.

Current diagnostic markers for pulmonary embolism (PE) are unspecific. We investigated the proteome of the exhaled breath condensate (EBC) in a porcine model of acute PE in order to identify putative diagnostic markers for PE. EBC was collected at baseline and after the induction of autologous intermediate-risk PE in 14 pigs, plus four negative control pigs. The protein profiles of the EBC were analyzed using label-free quantitative nano liquid chromatography-tandem mass spectrometry. A total of 897 proteins were identified in the EBCs from the pigs. Alterations were found in the levels of 145 different proteins after PE compared with the baseline and negative controls: albumin was among the most upregulated proteins, with 14-fold higher levels 2.5 h after PE (p-value: 0.02). The levels of 49 other proteins were between 1.3- and 17.1-fold higher after PE. The levels of 95 proteins were lower after PE. Neutrophil gelatinase-associated lipocalin (fold change 0.3, p-value < 0.01) was among the most reduced proteins 2.5 h after PE. A prediction model based on penalized regression identified five proteins including albumin and neutrophil gelatinase-associated lipocalin. The model was capable of discriminating baseline samples from EBC samples collected 2.5 h after PE correctly in 22 out of 27 samples. In conclusion, the EBC from pigs with acute PE contained several putative diagnostic markers of PE.

Internal Rotation Stress Test Reduces Cross-Pinning and Improves Outcomes in Displaced Pediatric Supracondylar Humeral Fractures.

Stabilization of the medial column is vital in preventing the loss of fixation and malunion in displaced pediatric supracondylar humeral fractures (SCHFs). The preferred percutaneous pin configuration for medial column fixation remains controversial between medial pinning (cross-pinning) and additional lateral-based pinning. The intraoperative internal rotation stress test (IRST) has been proposed to reliably determine the optimal fixation strategy for each unique fracture. This study evaluated the impact of implementing the IRST on both the choice of pin configuration and institution-wide complications in pediatric patients treated operatively for SCHFs. METHODS: Pediatric patients undergoing percutaneous pinning for SCHFs between 2007 and 2017 at a single center were retrospectively reviewed. The IRST was made a universal institutional practice in 2013. Patients were divided into 2 groups for analysis: (1) patients who underwent treatment before the IRST was implemented in 2013 (the pre-IRST group), and (2) patients who were treated after the IRST was implemented in 2013 (the IRST group). Subgroup analysis was completed for patients in the IRST group who were treated with cross-pinning or 3 lateral-based pins. RESULTS: In this study, 820 patients in the pre-IRST group and 636 patients in the IRST group were included. After the IRST implementation, the rate of loss of fixation fell from 1.2% to 0% (p = 0.003), and the reoperation rate fell from 3.3% to 0.2% (p < 0.001). No cases resulted in a loss of fixation after the adoption of the IRST. The number of patients treated with cross-pinning decreased significantly from 53.2% to 31.6% (p < 0.001) after the IRST implementation, yet cross-pinning continued to be used for more severe fractures. Complication rates within the IRST group were not significantly different (p > 0.05) between cross-pinning and 3 lateral-based pins. CONCLUSIONS: In the largest cohort reported on to date, to our knowledge, institutional implementation of the IRST resulted in a significant reduction in the use of cross-pinning. Although the usage of cross-pinning decreased, cross-pinning was still used frequently in the most severe fractures. The IRST use also resulted in significantly fewer complications such as loss of fixation after institution-wide implementation of the IRST for treating pediatric SCHFs. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Factors That Drive Annual Variation in Pediatric Elbow Fracture Occurrence, Severity, and Resource Utilization.

BACKGROUND: Elbow fractures are the most common pediatric fractures requiring operative treatment. To date, few studies have examined what annual factors drive pediatric elbow fracture incidence and no studies have examined which annual factors drive elbow fracture severity or resource utilization. The goal of this study was to not only document the annual patterns of pediatric elbow fracture incidence and severity but also the impact of these patterns on resource utilization in the emergency department, emergency medical service transportation, and the operating room (OR). METHODS: Retrospective cohort study of 4414 pediatric elbow fractures from a single tertiary hospital (2007 to 2017). Exclusion criteria included outside treatment or lack of diagnosis by an orthopaedist. Presentation information, injury patterns, transport, and treatment requirements were collected. Pearson correlations were used to analyze factors influencing fracture incidence, severity, and resource utilization. RESULTS: Pediatric elbow fracture incidence positively correlated with monthly daylight hours, but significantly fewer elbow fractures occurred during summer vacation from school compared with surrounding in school months. While fewer overall fractures occurred during summer break, the fractures sustained were greater in severity, conferring higher rates of displacement, higher risk of neurovascular injury, and greater needs for emergency transportation and operative treatment. Yearly, elbow fractures required 320.6 OR hours (7.7% of all pediatric orthopaedic OR time and 12.3% of all pediatric orthopaedic operative procedures), 203.4 hospital admissions, and a total of 4753.7 miles traveled by emergency medical service transportation to manage. All-cause emergency department visits were negatively correlated with daylight hours, inversing the pattern seen in elbow fractures. CONCLUSION: Increased daylight, while school was in session, was a major driver of the incidence of pediatric elbow fractures. While summer vacation conferred fewer fractures, these were of higher severity. As such, increased daylight correlated strongly with monthly resource utilization, including the need for emergency transportation and operative treatment. This study provides objective data by which providers and administrators can more accurately allocate resources. LEVEL OF EVIDENCE: Level III-Retrospective comparative study.

Levosimendan, milrinone, and dobutamine in experimental acute pulmonary embolism.

Acute pulmonary embolism is a frequent condition in emergency medicine and potentially fatal. Cause of death is right ventricular failure due to increased right ventricular afterload from both pulmonary vascular obstruction and vasoconstriction. Inodilators are interesting drugs of choice as they may improve right ventricular function and lower its afterload. We aimed to investigate the cardiovascular effects of three clinically relevant inodilators: levosimendan, milrinone, and dobutamine in acute pulmonary embolism. We conducted a randomized, blinded, animal study using 18 female pigs. Animals received large autologous pulmonary embolism until doubling of baseline mean pulmonary arterial pressure and were randomized to increasing doses of each inodilator. Effects were evaluated with bi-ventricular pressure-volume loop recordings, right heart catheterization, and blood gas analyses. Induction of pulmonary embolism increased right ventricular afterload and pulmonary pressure (p < 0.05) causing right ventricular dysfunction. Levosimendan and milrinone showed beneficial hemodynamic profiles by lowering right ventricular pressures and volume (p < 0.001) and improved right ventricular function and cardiac output (p < 0.05) without increasing right ventricular mechanical work. Dobutamine increased right ventricular pressure and function (p < 0.01) but at a cost of increased mechanical work at the highest doses, showing an adverse hemodynamic profile. In a porcine model of acute pulmonary embolism, levosimendan and milrinone reduced right ventricular afterload and improved right ventricular function, whereas dobutamine at higher doses increased right ventricular afterload and right ventricular mechanical work. The study motivates clinical testing of inodilators in patients with acute pulmonary embolism and right ventricular dysfunction.

Closed Chest Biventricular Pressure-Volume Loop Recordings with Admittance Catheters in a Porcine Model.

Pressure-volume (PV) loop recording enables the state-of-the-art investigation of load-independent variables of ventricular performance. Uni-ventricular evaluation is often performed in preclinical research. However, the right and left ventricles exert functional interdependence due to their parallel and serial connections, encouraging simultaneous evaluation of both ventricles. Furthermore, various pharmacological interventions may affect the ventricles and their preloads and afterloads differently. We describe our closed chest approach to admittance-based bi-ventricular PV loop recordings in a porcine model of acute right ventricular (RV) overload. We utilize minimally invasive techniques with all vascular accesses guided by ultrasound. PV catheters are positioned, under fluoroscopic guidance, to avoid thoracotomy in animals, as the closed chest approach maintains the relevant cardiopulmonary physiology. The admittance technology provides real-time PV loop recordings without the need for post-hoc processing. Furthermore, we explain some essential troubleshooting steps during critical timepoints of the presented procedure. The presented protocol is a reproducible and physiologically relevant approach to obtain a bi-ventricular cardiac PV loop recording in a large animal model. This can be applied to a large variety of cardiovascular animal research.

Extracting Medical Information from Paper COVID-19 Assessment Forms.

OBJECTIVE: This study examines the validity of optical mark recognition, a novel user interface, and crowdsourced data validation to rapidly digitize and extract data from paper COVID-19 assessment forms at a large medical center. METHODS: An optical mark recognition/optical character recognition (OMR/OCR) system was developed to identify fields that were selected on 2,814 paper assessment forms, each with 141 fields which were used to assess potential COVID-19 infections. A novel user interface (UI) displayed mirrored forms showing the scanned assessment forms with OMR results superimposed on the left and an editable web form on the right to improve ease of data validation. Crowdsourced participants validated the results of the OMR system. Overall error rate and time taken to validate were calculated. A subset of forms was validated by multiple participants to calculate agreement between participants. RESULTS: The OMR/OCR tools correctly extracted data from scanned forms fields with an average accuracy of 70% and median accuracy of 78% when the OMR/OCR results were compared with the results from crowd validation. Scanned forms were crowd-validated at a mean rate of 157 seconds per document and a volume of approximately 108 documents per day. A randomly selected subset of documents was reviewed by multiple participants, producing an interobserver agreement of 97% for documents when narrative-text fields were included and 98% when only Boolean and multiple-choice fields were considered. CONCLUSION: Due to the COVID-19 pandemic, it may be challenging for health care workers wearing personal protective equipment to interact with electronic health records. The combination of OMR/OCR technology, a novel UI, and crowdsourcing data-validation processes allowed for the efficient extraction of a large volume of paper medical documents produced during the COVID-19 pandemic.

Pulmonary vasodilation by sildenafil in acute intermediate-high risk pulmonary embolism: a randomized explorative trial.

BACKGROUND: To investigate if acute pulmonary vasodilation by sildenafil improves right ventricular function in patients with acute intermediate-high risk pulmonary embolism (PE). METHODS: Single center, explorative trial. Patients with PE were randomized to a single oral dose of sildenafil 50 mg (n = 10) or placebo (n = 10) as add-on to conventional therapy. The time from hospital admission to study inclusion was 2.3 ± 0.7 days. Right ventricular function was evaluated immediately before and shortly after (0.5-1.5 h) randomization by right heart catheterization (RHC), trans-thoracic echocardiography (TTE), and cardiac magnetic resonance (CMR). The primary efficacy endpoint was cardiac index measured by CMR. RESULTS: Patients had acute intermediate-high risk PE verified by computed tomography pulmonary angiography, systolic blood pressure of 135 ± 18 (mean ± SD) mmHg, increased right ventricular/left ventricular ratio 1.1 ± 0.09 and increased troponin T 167 ± 144 ng/L. Sildenafil treatment did not improve cardiac index compared to baseline (0.02 ± 0.36 l/min/m2, p = 0.89) and neither did placebo (0.00 ± 0.34 l/min/m2, p = 0.97). Sildenafil lowered mean arterial blood pressure (- 19 ± 10 mmHg, p < 0.001) which was not observed in the placebo group (0 ± 9 mmHg, p = 0.97). CONCLUSION: A single oral dose of sildenafil 50 mg did not improve cardiac index but lowered systemic blood pressure in patients with acute intermediate-high risk PE. The time from PE to intervention, a small patient sample size and low pulmonary vascular resistance are limitations of this study that should be considered when interpreting the results. TRIAL REGISTRATION: The trial was retrospectively registered at www.clinicaltrials.gov (NCT04283240) February 2nd 2020, https://clinicaltrials.gov/ct2/show/NCT04283240?term=NCT04283240&draw=2&rank=1 .

Exhaled breath condensate in acute pulmonary embolism; a porcine study of effect of condensing temperature and feasibility of protein analysis by mass spectrometry.

The search for diagnostic biomarkers for pulmonary embolism (PE) has mainly been focused on blood samples. Exhaled breath condensate (EBC) is a possible source for biomarkers specific for chronic lung diseases and cancer, yet no previous studies have investigated the potential of EBC for diagnosis of PE. The protein content in the EBC is very low, and efficient condensing of the EBC is important in order to obtain high quality samples for protein analysis. We investigated if advanced proteomic techniques in a porcine model of acute intermediate-high-risk PE was feasible using two different condensing temperatures for EBC collection. Seven pigs were anaesthetized and intubated. EBC was collected one hour after intubation. Two autologous emboli were induced through the right external jugular vein. Two hours after the emboli were administered, EBC was collected again. Condensing temperature was either -21 °C or -80 °C. Nano liquid chromatography-tandem mass spectrometry (nLC-MS/MS) was used to identify and quantify proteins of the EBC. A condensing temperature of -80 °C significantly increased the EBC volume compared with -21 °C (1.78 ± 0.25 ml vs 0.71 ± 0.12 ml) while the protein concentration in the EBC was unaltered. The mean protein concentration in the EBCs was 5.85 ± 0.93µg ml-1, unaltered after PE. In total, 254 proteins were identified in the EBCs. Identified proteins included proteins of the cytoplasm, nucleus, plasma membrane and extracellular region. The protein composition did not differ according to condensing temperature. The EBC from pigs with acute intermediate-high-risk PE contained sufficient amounts of protein for analysis by nLC-MS/MS. The proteins were from relevant cellular compartments, indicating that EBC is a possible source for biomarkers for acute PE.

Animal models of right heart failure.

Right heart failure may be the ultimate cause of death in patients with acute or chronic pulmonary hypertension (PH). As PH is often secondary to other cardiovascular diseases, the treatment goal is to target the underlying disease. We do however know, that right heart failure is an independent risk factor, and therefore, treatments that improve right heart function may improve morbidity and mortality in patients with PH. There are no therapies that directly target and support the failing right heart and translation from therapies that improve left heart failure have been unsuccessful, with the exception of mineralocorticoid receptor antagonists. To understand the underlying pathophysiology of right heart failure and to aid in the development of new treatments we need solid animal models that mimic the pathophysiology of human disease. There are several available animal models of acute and chronic PH. They range from flow induced to pressure overload induced right heart failure and have been introduced in both small and large animals. When initiating new pre-clinical or basic research studies it is key to choose the right animal model to ensure successful translation to the clinical setting. Selecting the right animal model for the right study is hence important, but may be difficult due to the plethora of different models and local availability. In this review we provide an overview of the available animal models of acute and chronic right heart failure and discuss the strengths and limitations of the different models.