Benjamin LZ Shou

All Publications

• Modified Thoracoabdominal Approach for the Repair of Massive Diaphragmatic Hernias. Annals of thoracic surgery short reports Shou, B. L., Dalal, A. R., Guenthart, B. A. 2026; 4 (2): 471-475

  Abstract

  Various approaches to treat large diaphragmatic hernias in adults are available depending on the extent of herniation, patient stability, and surgeon experience. We present a 2-case series of massive diaphragmatic hernia repairs using a modified thoracoabdominal technique whereby a stabilizing myocutaneous bridge is left between the thoracotomy and laparotomy incisions. This technique maintains excellent exposure, may be accomplished for either right- or left-sided hernias, and spares a portion of unaffected diaphragm.

  View details for DOI 10.1016/j.atssr.2025.12.008

  View details for PubMedID 42267034

  View details for PubMedCentralID PMC13245284

• Re-evaluating the association between thrombocytopenia and bleeding in extracorporeal membrane oxygenation (ECMO) PERFUSION-UK Leng, A., Rando, H., Shah, M., Akbar, A., Shou, B., Kalra, A., Cho, S., Whitman, G. J. R., HERALD Investigators 2026; 41 (4): 392-400

  Abstract

  ObjectivesThe platelet trigger at which to transfuse platelets to prevent bleeding complications in patients supported with extracorporeal membrane oxygenation (ECMO) is unclear. We aimed to elucidate the association between platelet count and bleeding sequelae in this patient population.MethodsWe conducted a single-center retrospective study of all adult patients who received ECMO support from 2017 to 2022. Patients were stratified into two groups: "non-thrombocytopenic" (>30 × 103 cells /μL) versus "thrombocytopenic" (≤30 × 103 cells /μL). Multivariable logistic regression was used to determine the association between thrombocytopenia and bleeding complications; covariates were selected a priori. A post-hoc analysis investigating platelet transfusion status and nadir platelet count as an ordinal variable was also performed.ResultsOf 291 VV- and VA-ECMO patients, 69 (24%) were categorized as "thrombocytopenic" and 144 (50%) experienced at least one major bleeding event. Compared to "non-thrombocytopenic" patients, "thrombocytopenic" patients were more likely to be male (p = 0.049), to require veno-arterial central canulation (p < 0.001), and to have been on dialysis (p < 0.001). Confounded by a 72% prophylactic transfusion rate, "Thrombocytopenia" was not associated with an increased risk of major bleeding (aOR: 0.59 [95% CI: 0.31-1.10]). However, in patients with a nadir platelet count between 31 and 50 × 103 cells/μL, the 63% with a prophylactic platelet transfusion had a significant reduction in major bleeding complications (p = 0.003).ConclusionsOur findings suggest that a platelet transfusion trigger of ≤50 × 103 cells/μL is of benefit for prophylaxis against bleeding during ECMO support.

  View details for DOI 10.1177/02676591251364481

  View details for Web of Science ID 001541489800001

  View details for PubMedID 40737699

• Pick Your Perfusion: National Outcomes of Normothermic Regional Perfusion versus Direct Procurement and Perfusion in Donation After Circulatory Death Cardiac Transplants Shou, B., Zhou, A., Goerlich, C., Hiesinger, W. MOSBY-ELSEVIER. 2026: S7-S8

  View details for DOI 10.1016/j.jtcvs.2026.03.075

  View details for Web of Science ID 001765305100013

• Ross after David: Management of the fused plane between the prior reimplantation valve-sparing aortic root replacement and the pulmonary autograft. JTCVS techniques Pedroza, A. J., Shou, B., Bustos, M., Liou, K., Woo, Y. J. 2025; 34: 84-87

  View details for DOI 10.1016/j.xjtc.2025.08.017

  View details for PubMedID 41368402

  View details for PubMedCentralID PMC12683042

• Ross after David: Management of the fused plane between the prior reimplantation valve-sparing aortic root replacement and the pulmonary autograft JTCVS TECHNIQUES Pedroza, A. J., Shou, B., Bustos, M., Liou, K., Woo, Y. 2025; 34: 84-87

  View details for DOI 10.1016/j.xjtc.2025.08.017

  View details for Web of Science ID 001630141800001

• Ex vivo optimization of a bicuspid pulmonary valve using the resequenced composite autograft Ross technique. JTCVS techniques Pedroza, A. J., Shou, B., Woo, Y. J. 2025; 33: 75-78

  View details for DOI 10.1016/j.xjtc.2025.07.005

  View details for PubMedID 41112433

  View details for PubMedCentralID PMC12529671

• Ex vivo optimization of a bicuspid pulmonary valve using the resequenced composite autograft Ross technique JTCVS TECHNIQUES Pedroza, A. J., Shou, B., Woo, Y. 2025; 33: 75-78

  View details for DOI 10.1016/j.xjtc.2025.07.005

  View details for Web of Science ID 001588856200015

• Enhancing Survival Prediction After Venoarterial Extracorporeal Membrane Oxygenation Using Machine Learning. ASAIO journal (American Society for Artificial Internal Organs : 1992) Leng, A., Bachina, P., Liu, O., Shou, B., Racz, C., Giliver, D. A., Shpitser, I., Whitman, G. J., Cho, S., HERALD Investigators 2025

  Abstract

  In-hospital mortality after venoarterial extracorporeal membrane oxygenation (VA-ECMO) remains high. This study compared the performance of the Survival after Venoarterial ECMO (SAVE) score with machine learning (ML) models incorporating rich electronic medical record data to evaluate survival for patients on VA-ECMO support. We retrospectively reviewed adults undergoing VA-ECMO (2016-2022) at a single tertiary care center. The CatBoost algorithm was trained using leave-one-out cross-validation (LOOCV) on 74 extracted vital signs, laboratory values, and ventilator settings. Shapley Additive Explanations (SHAP) was used to identify key predictive features for logistic regression. Overall, 194 VA-ECMO patients (median age = 58 years, 36.6% female) were included, with 133 (69%) experiencing mortality. The SAVE score was compared to two predictive models: a pre-ECMO model (≤ 24 hours before cannulation) and an on-ECMO model (including up to the first 48 hours of ECMO). The LOOCV area under the receiver-operator characteristics curves (AUC) for the SAVE score, pre-ECMO, and on-ECMO models was 0.73, 0.77, and 0.83, respectively. Logistic regressions using ML-identified variables showed stepwise AUC improvements: 0.82 (pre-ECMO), 0.86 (on-ECMO), and 0.89 (combined). A novel, interpretable ML model predicted survival for VA-ECMO patients with accuracy comparable to the SAVE score. Incorporating on-ECMO variables significantly increased predictive performance and revealed novel variables associated with survival.

  View details for DOI 10.1097/MAT.0000000000002475

  View details for PubMedID 40454690

• Concurrent aortic valve replacement and splenectomy for Q-fever endocarditis with massive splenomegaly and pancytopenia. JTCVS techniques Weininger, G., Pedroza, A. J., Shou, B. L., Forrester, J. D., Lin, Y. 2025; 30: 73-76

  View details for DOI 10.1016/j.xjtc.2025.01.021

  View details for PubMedID 40242106

  View details for PubMedCentralID PMC11998301

• A Novel, Interpretable Machine Learning Model to Predict Neurological Outcomes Following Venoarterial Extracorporeal Membrane Oxygenation. Neurocritical care Shou, B. L., Leng, A., Bachina, P., Kalra, A., Zhou, A. L., Whitman, G., Cho, S., HERALD Investigators 2025

  Abstract

  BACKGROUND: We used machine learning models incorporating rich electronic medical record (EMR) data to predict neurological outcomes after venoarterial extracorporeal membrane oxygenation (VA-ECMO).METHODS: This was a retrospective review of adult (≥18years) patients undergoing VA-ECMO between 6/2016 and 4/2022 at a single center. The primary outcome was good neurological outcome, defined as a modified Rankin Scale score of 0 to 3, evaluated at hospital discharge. We extracted every measurement of 74 vital and laboratory values, as well as circuit and ventilator settings, from 24h before cannulation through the entire duration of ECMO. An XGBoost model with Shapley Additive Explanations was developed and evaluated with leave-one-out cross-validation.RESULTS: Overall, 194 patients undergoing VA-ECMO (median age 58years, 63% male) were included. We extracted more than 14 million individual data points from the EMR. Of 194 patients, 39 patients (20%) had good neurological outcomes. Three models were generated: model A, which contained only pre-ECMO data; model B, which added data from the first 48h of ECMO; and model C, which included data from the entire ECMO run. The leave-one-out cross-validation area under the receiver operator characteristics curves for models A, B, and C were 0.72, 0.81, and 0.90, respectively. The inclusion of on-ECMO physiologic, laboratory, and circuit data greatly improved model performance. Both modifiable and nonmodifiable variables, such as lower body mass index, lower age, higher mean arterial pressure, and higher hemoglobin, were associated with good neurological outcome.CONCLUSIONS: An interpretable machine learning model from EMR-extracted data was able to predict neurological outcomes for patients undergoing VA-ECMO with excellent accuracy.

  View details for DOI 10.1007/s12028-025-02233-0

  View details for PubMedID 40148658

• Advancements in Computed Tomography Analysis for Thoracic Aortic Surgery: The Expanding Role of Automation HEART SURGERY FORUM Chatterjee, D., Singh, S., Shou, B. L. 2025; 28 (8): E644-E655

  View details for DOI 10.59958/hsf.8381

  View details for Web of Science ID 001569166300008

• Impact of Extracorporeal Membrane Oxygenation Bridging Duration on Lung Transplant Outcomes ANNALS OF THORACIC SURGERY Shou, B. L., Kalra, A., Zhou, A. L., Barbur, I., McGoldrick, M., Larson, E., Keller, S. P., Kim, B., Whitman, G. J. R., Cho, S., Bush, E. L. 2024; 118 (2): 496-503

  Abstract

  We sought to characterize the association between venovenous extracorporeal membrane oxygenation (VV-ECMO) bridging duration and outcomes in patients listed for lung transplantation.A retrospective observational study was conducted using the Organ Procurement and Transplantation Network (OPTN) database to identify adults (aged ≥18 years) who were listed for lung transplantation between 2016 and 2020 and were bridged with VV-ECMO. Patients were then stratified into groups, determined by risk inflection points, depending on the amount of time spent on pretransplant ECMO: group 1 (≤5 days), group 2 (6-10 days), group 3 (11-20 days), and group 4 (>20 days). Waiting list survival between groups was analyzed using Fine-Gray competing risk models. Posttransplant survival was compared using Cox regression.Of 566 eligible VV-ECMO bridge-to-lung-transplant patients (median age, 54 years, 49% men), 174 (31%), 124 (22%), 130 (23%), and 138 (24%) were categorized as groups 1, 2, 3, and 4, respectively. Overall, median duration of VV-ECMO was 10 days (interquartile range, 1-211 days), and 178 patients (31%) died on the waiting list. In the Fine-Gray model, compared with group 1, patients bridged with longer ECMO durations in group 2 (subdistribution hazard ratio [SHR], 2.95; 95% CI, 1.63-5.35), group 3 (SHR, 3.96; 95% CI, 2.36-6.63), and group 4 (SHR, 4.33; 95% CI, 2.59-7.22, all P < .001) were more likely to die on the waiting list. Of 388 patients receiving a transplant, pretransplant ECMO duration was not associated with 1-year survival in Cox regression.Prolonged duration of ECMO bridging was associated with worse waiting list mortality but did not impact survival after lung transplant. Prioritization of very early transplantation may improve waiting list outcomes in this population.

  View details for DOI 10.1016/j.athoracsur.2024.04.021

  View details for Web of Science ID 001278300600001

  View details for PubMedID 38740080

  View details for PubMedCentralID PMC11284668

• Impact of Heart Failure Etiology on Waitlist Mortality in Heart Transplant Candidates Supported With Extracorporeal Membrane Oxygenation CLINICAL TRANSPLANTATION Shah, M. M., Rodriguez, E., Shou, B. L., Jenkins, R. T., Rando, H., Kilic, A. 2024; 38 (8): e15421

  Abstract

  Extracorporeal membrane oxygenation (ECMO) has gained traction as a bridge to heart transplantation (HT) but remains associated with increased waitlist mortality. This study explores whether this risk is modified by underlying heart failure (HF) etiology.Using the Organ Procurement and Transplantation Network registry, we conducted a retrospective review of first-time adult HT candidates from 2018 through 2022. Patients were categorized as "ECMO", if ECMO was utilized during the waitlisting period, or "No ECMO" otherwise. Patients were then stratified according to the following HF etiology: ischemic cardiomyopathy (CMP), dilated nonischemic CMP, restrictive CMP, hypertrophic CMP, and congenital heart disease (CHD). After baseline comparisons, waitlist mortality was characterized for ECMO and HF etiology using the Fine-Gray regression.A total of 16 143 patients were identified of whom 7.0% (n = 1063) were bridged with ECMO. Compared to No ECMO patients, ECMO patients had shorter waitlist durations (46.3 vs. 185.0 days, p < 0.01) and were more likely to undergo transplantation (75.3% vs. 70.3%, p < 0.01). Outcomes analysis revealed that ECMO was associated with increased mortality risk (subdistribution hazard ratio [SHR]: 3.42, p < 0.01), a risk that persisted in all subgroups and was notably high in CHD (SHR: 4.83, p < 0.01) and hypertrophic CMP (SHR: 9.78, p < 0.01). HF etiology comparison within ECMO patients revealed increased mortality risk with CHD (SHR: 3.22, p < 0.01). Within No ECMO patients, hypertrophic CMP patients had lower mortality risk (SHR: 0.64, p = 0.03).The increased waitlist mortality risk with ECMO persisted after stratification by HF etiology. These findings can help decision-making surrounding candidacy for cannulation and prognostic evaluation.

  View details for DOI 10.1111/ctr.15421

  View details for Web of Science ID 001291179400001

  View details for PubMedID 39140404

• The impact of local programmatic decisions on outcomes in transplant-listed adults with congenital heart disease. Journal of cardiac failure Akbar, A. F., Shou, B. L., Kilic, A., Cedars, A. M. 2024

  Abstract

  BACKGROUND: We investigated variables impacting waitlist time and negative waitlist outcomes in adult congenital heart disease (ACHD) orthotopic heart transplant (OHT) candidates following the 2018 allocation change.METHODS: Adult OHT candidates listed between 10/18/2018-12/31/2022 in the United Network for Organ Sharing database were categorized as ACHD vs. non-ACHD. Waitlist time and time to upgrade for those upgraded into status 1-3 were compared using rank-sum tests. Death/delisting for deterioration was assessed using Fine-Gray sub-distribution hazard ratios (SHRs).RESULTS: Of 15,424 OHT candidates, 589 (3.8%) were ACHD. ACHD vs. non-ACHD candidates had less urgent status at initial listing (4.2% vs. 4.7% listed at status 1; 17.2% vs. 23.7% listed at status 2, p<0.001), but not final listing (5.9% vs. 7.6% final status 1; 35.6% vs. 36.8% final status 2, p<0.001). ACHD vs. non-ACHD candidates upgraded into status 1 (65.0 vs. 30.0 days, p=0.09) and status 2 (113.0 vs. 64.0 days, p=0.003) spent longer on the waitlist. ACHD vs. non-ACHD candidates spent longer waiting for an upgrade into status 1 (51.4 vs. 17.6 days, p=0.027) and status 2 (76.7 vs. 34.7 days, p=0.003). Once upgraded, there was no difference between groups in waitlist time as status 1 (9.7 vs. 5.5 days, p=0.66). ACHD vs. non-ACHD candidates with a final status of 1 (20.0% vs. 8.6%; SHR 2.47 [95%CI=1.19-5.16], p=0.02) and 2 (8.9% vs. 2.3%; SHR 3.59 [95%CI=2.18-5.91], p<0.001) experienced higher death/deterioration.CONCLUSIONS: ACHD candidates have longer waitlist times, lower priority status at initial listing, wait longer for upgrade, and have higher mortality at the same final status as non-ACHD candidates, suggesting that they are being upgraded too late.

  View details for DOI 10.1016/j.cardfail.2024.04.001

  View details for PubMedID 38616008

• Trends on Near-Infrared Spectroscopy Associated With Acute Brain Injury in Venoarterial Extracorporeal Membrane Oxygenation ASAIO JOURNAL Zhao, D., Shou, B. L., Caturegli, G., Whitman, G. J. R., Kim, B., Cho, S. 2023; 69 (12): 1083-1089

  Abstract

  We aimed to determine the association between cerebral regional oxygen saturation (rSO 2 ) trends from cerebral near-infrared spectroscopy (cNIRS) and acute brain injury (ABI) in adult venoarterial extracorporeal membrane oxygenation (VA-ECMO) patients. ABI was defined as intracranial hemorrhage, ischemic stroke, hypoxic ischemic brain injury, or brain death during ECMO. rSO 2 values were collected from left and right cerebral oximetry sensors every hour from ECMO cannulation. Cerebral desaturation was defined as consecutive hours of rSO 2 < 40%. rSO 2 asymmetry was determined by (a) averaging left/right rSO 2 difference over the entire ECMO run; (b) consecutive hours of rSO 2 asymmetry. Sixty-nine VA-ECMO patients (mean age 56 years, 65% male) underwent cNIRS. Eighteen (26%) experienced ABI. When the mean rSO 2 asymmetry was >8% there was significantly increased odds of ABI (aOR = 39.4; 95% CI = 4.1-381.4). Concurrent rSO 2 < 40% and rSO 2 asymmetry >10% for >10 consecutive hours (asymmetric desaturation) was also significantly associated with ABI (aOR = 5.2; 95% CI = 1.2-22.2), but neither criterion alone were. Mean rSO 2 asymmetry>8% exhibited 39% sensitivity and 98% specificity for detecting ABI, with an area under the curve (AUC) of 0.86, and asymmetric desaturation had 33% sensitivity and 88% specificity, with an AUC of 0.72. These trends on NIRS monitoring may help detect ABI in VA-ECMO patients.

  View details for DOI 10.1097/MAT.0000000000002032

  View details for Web of Science ID 001186852400006

  View details for PubMedID 37556554

  View details for PubMedCentralID PMC10843160

• What Factors Are Associated With Arterial Line-Related Limb Ischemia in Patients on Extracorporeal Membrane Oxygenation? A Single- Center Retrospective Cohort Study JOURNAL OF CARDIOTHORACIC AND VASCULAR ANESTHESIA Shu, H. T., Covarrubias, O., Shah, M. M., Muquit, S. T., Yang, V. B., Zhao, X., Kagabo, W., Shou, B. L., Kalra, A., Whitman, G., Kim, B., Cho, S., LaPorte, D. M., Shafiq, B., Hopkins Educ Res Adv Life Support 2023; 37 (12): 2489-2498

  Abstract

  The primary purpose of this study was to identify factors associated with the development of arterial line-related limb ischemia in patients on extracorporeal membrane oxygenation (ECMO). The authors also sought to characterize and report the outcomes of patients who developed arterial line-related limb ischemia.Retrospective cohort study.A single academic tertiary referral ECMO center.Consecutive patients who were treated with ECMO over 6 years.Use of arterial line.A total of 278 consecutive ECMO patients were included, with 19 (7%) patients developing arterial line-related limb ischemia during the ECMO run. Postcannulation Sequential Organ Failure Assessment (SOFA) (adjusted odds ratio [aOR] 1.20, 95% CI 1.08-1.32), Acute Physiology and Chronic Health Evaluation-II (aOR 0.84, 95% CI 0.74-0.95), and adjusted Vasopressor Dose Equivalence (aOR 1.03, 95% CI 1.01-1.05) scores were independently associated with the development of arterial line-associated limb ischemia. A SOFA score of ≥17 at the time of ECMO cannulation had an 80% sensitivity and 87% specificity for predicting arterial line-related limb ischemia.Arterial line-related limb ischemia is much more common in ECMO patients than in the typical intensive care unit setting. The SOFA score may be useful in identifying which patients may be at risk for arterial line-related limb ischemia. As this was a single-center retrospective study, these results are inherently exploratory, and prospective multicenter studies are necessary to validate these results.

  View details for DOI 10.1053/j.jvca.2023.08.131

  View details for Web of Science ID 001109714500001

  View details for PubMedID 37735020

• Impact of intraoperative blood products, fluid administration, and persistent hypothermia on bleeding leading to reexploration after cardiac surgery. The Journal of thoracic and cardiovascular surgery Shou, B. L., Zhou, A. L., Ong, C. S., Alejo, D. E., DiNatale, J. M., Larson, E. L., Lawton, J. S., Schena, S. 2023

  Abstract

  OBJECTIVE: Risk factors for severe postoperative bleeding after cardiac surgery remain multiple and incompletely elucidated. We evaluated the impact of intraoperative blood product transfusions, intravenous fluid administration, and persistently low core body temperature (CBT) at intensive care unit arrival on risk of perioperative bleeding leading to reexploration.METHODS: We retrospectively queried our tertiary care center's Society of Thoracic Surgeons Institutional Database for all index, on-pump, adult cardiac surgery patients between July 2016 and September 2022. Intraoperative fluid (crystalloid and colloid) and blood product administrations, as well as perioperative CBT data, were harvested from electronic medical records. Linear and nonlinear mixed models, treating surgeon as a random effect to account for inter-surgeon practice differences, were used to assess the association between above factors and reexploration for bleeding.RESULTS: Of 4037 patients, 151 (3.7%) underwent reexploration for bleeding. Reexplored patients experienced remarkably greater postoperative morbidity (23% vs 6%, P<.001) and 30-day mortality (14% vs 2%, P<.001). In linear models, progressively increasing IV crystalloid administration (adjusted odds ratio, 1.11, 95% confidence interval, 1.03-1.19) and decreasing CBT on intensive care unit arrival (adjusted odds ratio, 1.20; 95% confidence interval, 1.05-1.37) were associated with greater risk of bleeding leading to reexploration. Nonlinear analysis revealed increasing risk after 6L of crystalloid administration and a U-shaped relationship between CBT and reexploration risk. Intraoperative blood product transfusion of any kind was not associated with reexploration.CONCLUSIONS: We found evidence of both dilution- and hypothermia-related effects associated with perioperative bleeding leading to reexploration in cardiac surgery. Interventions targeting modification of such risk factors may decrease the rate this complication.

  View details for DOI 10.1016/j.jtcvs.2023.10.011

  View details for PubMedID 37839660

• Risk Factors for Nondiagnostic Imaging in a Real-World Deployment of Artificial Intelligence Diabetic Retinal Examinations in an Integrated Health care System: Maximizing Workflow Efficiency Through Predictive Dilation JOURNAL OF DIABETES SCIENCE AND TECHNOLOGY Shou, B. L., Venkatesh, K., Chen, C., Ghidey, R., Lee, J., Wang, J., Channa, R., Wolf, R. M., Abramoff, M. D., Liu, T. 2023: 302-308

  Abstract

  In the pivotal clinical trial that led to Food and Drug Administration De Novo "approval" of the first fully autonomous artificial intelligence (AI) diabetic retinal disease diagnostic system, a reflexive dilation protocol was used. Using real-world deployment data before implementation of reflexive dilation, we identified factors associated with nondiagnostic results. These factors allow a novel predictive dilation workflow, where patients most likely to benefit from pharmacologic dilation are dilated a priori to maximize efficiency and patient satisfaction.Retrospective review of patients who were assessed with autonomous AI at Johns Hopkins Medicine (8/2020 to 5/2021). We constructed a multivariable logistic regression model for nondiagnostic results to compare characteristics of patients with and without diagnostic results, using adjusted odds ratio (aOR). P < .05 was considered statistically significant.Of 241 patients (59% female; median age = 59), 123 (51%) had nondiagnostic results. In multivariable analysis, type 1 diabetes (T1D, aOR = 5.82, 95% confidence interval [CI]: 1.45-23.40, P = .01), smoking (aOR = 2.86, 95% CI: 1.36-5.99, P = .005), and age (every 10-year increase, aOR = 2.12, 95% CI: 1.62-2.77, P < .001) were associated with nondiagnostic results. Following feature elimination, a predictive model was created using T1D, smoking, age, race, sex, and hypertension as inputs. The model showed an area under the receiver-operator characteristics curve of 0.76 in five-fold cross-validation.We used factors associated with nondiagnostic results to design a novel, predictive dilation workflow, where patients most likely to benefit from pharmacologic dilation are dilated a priori. This new workflow has the potential to be more efficient than reflexive dilation, thus maximizing the number of at-risk patients receiving their diabetic retinal examinations.

  View details for DOI 10.1177/19322968231201654

  View details for Web of Science ID 001193603900001

  View details for PubMedID 37798955

  View details for PubMedCentralID PMC10973867

• Early United States experience with lung donation after circulatory death using thoracoabdominal normothermic regional perfusion JOURNAL OF HEART AND LUNG TRANSPLANTATION Zhou, A. L., Ruck, J. M., Casillan, A. J., Larson, E. L., Shou, B. L., Karius, A. K., Ha, J. S., Shah, P. D., Merlo, C. A., Bush, E. L. 2023; 42 (6): 693-696

  Abstract

  Thoracoabdominal normothermic regional perfusion (TA-NRP) has recently begun being utilized in the United States for recovery of cardiothoracic allografts from some donors after circulatory death (DCD), but data on lungs recovered in this method is limited to case reports. We conducted a national retrospective review of lung transplants from DCD donors recovered using TA-NRP. Of the 434 total DCD lung transplants performed between January 2020 and March 2022, 17 were recovered using TA-NRP. Compared to direct recovery DCD transplants, recipients of TA-NRP DCD transplants had lower likelihood of ventilation >48 hours (23.5% vs 51.3%, p = 0.027) and similar likelihood of predischarge acute rejection, requirement for extracorporeal membrane oxygenation at 72 hours, hospital lengths of stay, and survival at 30, 60, and 90 days post-transplant. These early data suggest that DCD lung recovery using TA-NRP might be a safe way to further expand the donor pool and warrant further study.

  View details for DOI 10.1016/j.healun.2023.03.001

  View details for Web of Science ID 001002265200001

  View details for PubMedID 36990867

  View details for PubMedCentralID PMC10192114

• Lower Oxygen Tension and Intracranial Hemorrhage in Veno-venous Extracorporeal Membrane Oxygenation LUNG Akbar, A., Shou, B., Feng, C., Zhao, D., Kim, B., Whitman, G., Bush, E., Cho, S., HERALD Investigators 2023; 201 (3): 315-320

  Abstract

  We examined the relationship between 24-h pre- and post-cannulation arterial oxygen tension (PaO2) and arterial carbon dioxide tension (PaCO2) and subsequent acute brain injury (ABI) in patients receiving veno-venous extracorporeal membrane oxygenation (VV-ECMO) with granular arterial blood gas (ABG) data and institutional standardized neuromonitoring.Eighty-nine patients underwent VV-ECMO (median age = 50, 63% male). Twenty (22%) patients experienced ABI; intracranial hemorrhage (ICH) was the most common diagnosis (n = 14, 16%). Lower post-cannulation PaO2 levels were significantly associated with ICH (66 vs. 81 mmHg, p = 0.007) and a post-cannulation PaO2 level < 70 mmHg was more frequent in these patients (71% vs. 33%, p = 0.007). PaCO2 parameters were not associated with ABI. By multivariable logistic regression, hypoxemia post-cannulation increased the odds of ICH (OR = 5.06, 95% CI:1.41-18.17; p = 0.01).In summary, lower oxygen tension in the 24-h post-cannulation was associated with ICH development. The precise roles of peri-cannulation ABG changes deserve further investigation, as they may influence the management of VV-ECMO patients.

  View details for DOI 10.1007/s00408-023-00618-6

  View details for Web of Science ID 000974442300001

  View details for PubMedID 37086285

  View details for PubMedCentralID PMC10578342

• National Trends, Risk Factors, and Outcomes of Acute In-hospital Stroke After Lung Transplantation in the United States: Analysis of the United Network for Organ Sharing Registry. Chest Shou, B. L., Wilcox, C., Florissi, I., Krishnan, A., Kim, B. S., Keller, S. P., Whitman, G. J., Uchino, K., Bush, E. L., Cho, S. 2023

  Abstract

  BACKGROUND: Lung transplantation is the definitive treatment for end-stage lung failure. However, there have been no large, long-term studies on the impact of acute in-hospital stroke in this population.RESEARCH QUESTION: What are the trends, risk factors, and outcomes of acute stroke in patients undergoing lung transplantation in the United States?STUDY DESIGN AND METHODS: We identified adult first-time, isolated lung transplant (LTx) recipients from the United Network for Organ Sharing (UNOS) database, which comprehensively captures every transplant in the United States, between 5/2005 and 12/2020. Stroke was defined as occurring at any time after LTx but prior to discharge. Multivariable logistic regression with stepwise feature elimination was used to identify risk factors for stroke. Freedom from death in stroke vs. non-stroke patients was evaluated with Kaplan-Meier analysis. Cox proportional hazards analysis was used to identify predictors of death at 24 months.RESULTS: Of 28,564 patients (median age=60, 60% male), 653 (2.3%) experienced an acute in-hospital stroke after LTx. Median follow-up was 1.2 (stroke) and 3.0 years (non-stroke). Annual incidence of stroke increased (1.5% in 2005 to 2.4% in 2020, p-trend=0.007), as did lung allocation score (LAS) and utilization of post-LTx extracorporeal membrane oxygenation (postLTX-ECMO) (p=0.01 and p<0.001, respectively). Compared to those without, patients with stroke had lower survival at 1-month (84% vs. 98%), 12-months (61% vs. 88%), and 24 months (52% vs. 80%, p (log-rank) <0.001 for all). In Cox analysis, acute stroke conferred a high hazard of mortality (HR=3.01, 95%CI=2.67-3.41). PostLTx-ECMO was the strongest risk factor for stroke (adjusted odds ratio=2.98, 95%CI=2.19-4.06).INTERPRETATION: Acute in-hospital stroke following lung transplantation has been increasing over time and is associated with markedly worse short- and long-term survival. As increasingly sicker patients receive lung transplantation as well as stroke, further research on stroke characteristics, prevention, and management strategies is warranted.

  View details for DOI 10.1016/j.chest.2023.04.007

  View details for PubMedID 37054775

• Arterial oxygen and carbon dioxide tension and acute brain injury in extracorporeal cardiopulmonary resuscitation patients: Analysis of the extracorporeal life support organization registry JOURNAL OF HEART AND LUNG TRANSPLANTATION Shou, B. L., Ong, C., Premraj, L., Brown, P., Tonna, J. E., Dalton, H. J., Kim, B., Keller, S. P., Whitman, G. J. R., Cho, S. 2023; 42 (4): 503-511

  Abstract

  Acute brain injury (ABI) remains common after extracorporeal cardiopulmonary resuscitation (ECPR). Using a large international multicenter cohort, we investigated the impact of peri-cannulation arterial oxygen (PaO2) and carbon dioxide (PaCO2) on ABI occurrence.We retrospectively analyzed adult (≥18 years old) ECPR patients in the Extracorporeal Life Support Organization registry from 1/2009 through 12/2020. Composite ABI included ischemic stroke, intracranial hemorrhage (ICH), seizures, and brain death. The registry collects 2 blood gas data pre- (6 hours) and post- (24 hours) cannulation. Blood gas parameters were classified as: hypoxia (<60mm Hg), normoxia (60-119mm Hg), and mild (120-199mm Hg), moderate (200-299mm Hg), and severe hyperoxia (≥300mm Hg); hypocarbia (<35mm Hg), normocarbia (35-44mm Hg), mild (45-54mm Hg) and severe hypercarbia (≥55mm Hg). Missing values were handled using multiple imputation. Multivariable logistic regression analysis was used to assess the relationship of PaO2 and PaCO2 with ABI.Of 3,125 patients with ECPR intervention (median age=58, 69% male), 488 (16%) experienced ABI (7% ischemic stroke; 3% ICH). In multivariable analysis, on-ECMO moderate (aOR=1.42, 95%CI: 1.02-1.97) and severe hyperoxia (aOR=1.59, 95%CI: 1.20-2.10) were associated with composite ABI. Additionally, severe hyperoxia was associated with ischemic stroke (aOR=1.63, 95%CI: 1.11-2.40), ICH (aOR=1.92, 95%CI: 1.08-3.40), and in-hospital mortality (aOR=1.58, 95%CI: 1.21-2.06). Mild hypercarbia pre-ECMO was protective of composite ABI (aOR=0.61, 95%CI: 0.44-0.84) and ischemic stroke (aOR=0.56, 95%CI: 0.35-0.89).Early severe hyperoxia (≥300mm Hg) on ECMO was a significant risk factor for ABI and mortality. Careful consideration should be given in early oxygen delivery in ECPR patients who are at risk of reperfusion injury.

  View details for DOI 10.1016/j.healun.2022.10.019

  View details for Web of Science ID 000966060000001

  View details for PubMedID 36435686

  View details for PubMedCentralID PMC10050131

• Early Reexploration for Bleeding Is Associated With Improved Outcome in Cardiac Surgery ANNALS OF THORACIC SURGERY Shou, B. L., Aravind, P., Ong, C., Alejo, D., Canner, J. K., Etchill, E. W., DiNatale, J., Prokupets, R., Esfandiary, T., Lawton, J. S., Schena, S. 2023; 115 (1): 232-239

  Abstract

  Reexploration after cardiac surgery, most frequently for bleeding, is a quality metric used to assess surgical performance. This may cause surgeons to delay return to the operating room in favor of attempting nonoperative management. This study investigated the impact of the timing of reexploration on morbidity and mortality.This study was a single-institution retrospective review of all adult cardiac surgery patients from July 2010 to June 2020. Time to reexploration was assessed, and outcomes were compared across increasing time intervals. Reported bleeding sites were classified into 5 groups, and bleeding rate (chest tube output) was compared across bleeding sites. Univariable analysis was performed using the Fisher exact and Kruskal-Wallis tests. Multivariable logistic regression models were used for risk-adjusted analyses.Of 10 070 eligible patients, 251 (2.5%) required reexploration for postoperative bleeding. The most common site of bleeding was "any suture line" (n = 70; 28%). Interestingly, in 30% of cases (n = 75) "no active bleeding" site was reported. The highest rate of bleeding (mL/h) was observed in the "any mediastinal structure" group (median, 450; interquartile range [IQR], 185, 8878), and the lowest rate was noted in the "no active bleeding" group (median, 151.2; IQR, 102, 270). Both morbidity rates (0-4 hours, 12.3% vs 25-48 hours, 37.5%; P = .001) and mortality rates (0-4 hours, 3.1% vs 25-48 hours, 43.8%; P = .001) escalated significantly with increasing time to reexploration.Delayed reexploration for bleeding after cardiac surgery is associated with increased risk for morbidity and mortality. Early surgical intervention, particularly within 4 hours, may improve outcomes. Implications from using reoperation as a performance metric may lead to unnecessary delay and patient harm.

  View details for DOI 10.1016/j.athoracsur.2022.07.037

  View details for Web of Science ID 000908689300001

  View details for PubMedID 35952856

• Perivascular fat attenuation for predicting adverse cardiac events in stable patients undergoing invasive coronary angiography JOURNAL OF CARDIOVASCULAR COMPUTED TOMOGRAPHY Chatterjee, D., Shou, B. L., Matheson, M. B., Ostovaneh, M. R., Rochitte, C., Chen, M. Y., Dewey, M., Ortman, J., Cox, C., Lima, J. A. C., Arbab-Zadeh, A. 2022; 16 (6): 483-490

  Abstract

  Inflammation surrounding the coronary arteries can be non-invasively assessed using pericoronary adipose tissue attenuation (PCAT). While PCAT holds promise for further risk stratification of patients with low coronary artery disease (CAD) prevalence, its value in higher risk populations remains unknown.CORE320 enrolled patients referred for invasive coronary angiography with known or suspected CAD. Coronary computed tomography angiography (CCTA) images were collected for 381 patients for whom clinical outcomes were assessed 5 years after enrollment. Using semi-automated image analysis software, PCAT was obtained and normalized for the right coronary (RCA), left anterior descending (LAD), and left circumflex arteries (LCx). The association between PCAT and major adverse cardiovascular events (MACE) during follow up was assessed using Cox regression models.Thirty-seven patients were excluded due to technical failure. For the remaining 344 patients, median age was 62 (interquartile range, 55-68) with 59% having ≥1 coronary artery stenosis of ≥50% by quantitative coronary angiography. Mean attenuation values for PCAT in RCA, LAD, and LCx were -74.9, -74.2, and -71.2, respectively. Hazard ratios and 95% confidence intervals (CI) for normalized PCAT in the RCA, LAD, and LCx for MACE were 0.96 (CI: 0.75-1.22, p ​= ​0.71), 1.31 (95% CI: 0.96-1.78, p ​= ​0.09), and 0.98 (95% CI: 0.78-1.22, p ​= ​0.84), respectively. For death, stroke, or myocardial infarction only, hazard ratios were 0.68 (0.44-1.07), 0.85 (0.56-1.29), and 0.57 (0.41-0.80), respectively.In patients referred for invasive coronary angiography with suspected CAD, PCAT did not predict MACE during long term follow up. Further studies are needed to understand the relationship of PCAT with CAD risk.

  View details for DOI 10.1016/j.jcct.2022.05.004

  View details for Web of Science ID 000905079700004

  View details for PubMedID 35680534

  View details for PubMedCentralID PMC9684349

• Arterial Carbon Dioxide and Acute Brain Injury in Venoarterial Extracorporeal Membrane Oxygenation ASAIO JOURNAL Shou, B. L. L., Ong, C., Zhou, A. L., Al-Kawaz, M. N. N., Etchill, E., Giuliano, K., Dong, J., Bush, E., Kim, B., Choi, C., Whitman, G., Cho, S. 2022; 68 (12): 1501-1507

  Abstract

  Acute brain injury (ABI) occurs frequently in patients receiving venoarterial extracorporeal membrane oxygenation (VA-ECMO). We examined the association between peri-cannulation arterial carbon dioxide tension (PaCO 2 ) and ABI with granular blood gas data. We retrospectively analyzed adult patients who underwent VA-ECMO at a tertiary care center with standardized neuromonitoring. Pre- and post-cannulation PaCO 2 were defined as the mean of all PaCO 2 values in the 12 hours before and after cannulation, respectively. Peri-cannulation PaCO 2 drop (∆PaCO 2 ) equaled pre- minus post-cannulation PaCO 2 . ABI included intracranial hemorrhage (ICH), ischemic stroke, hypoxic-ischemic brain injury, cerebral edema, seizure, and brain death. Univariable logistic regression analysis was performed for the presence of ABI. Out of 129 VA-ECMO patients (median age = 60, 63% male), 43 (33%) patients experienced ABI. Patients had a median of 11 (interquartile range: 8-14) peri-cannulation PaCO 2 values. Comparing patients with and without ABI, pre-cannulation (39 vs. 42 mm Hg; p = 0.38) and post-cannulation (37 vs. 36 mm Hg; p = 0.82) PaCO 2 were not different. However, higher pre-cannulation PaCO 2 (odds ratio [OR] = 2.10; 95% confidence interval [CI] = 1.10-4.00; p = 0.02) and larger ∆PaCO 2 (OR = 2.69; 95% CI = 1.18-6.13; p = 0.02) were associated with ICH. In conclusion, in a cohort with granular arterial blood gas (ABG) data and a standardized neuromonitoring protocol, higher pre-cannulation PaCO 2 and larger ∆PaCO 2 were associated with increased prevalence of ICH.

  View details for DOI 10.1097/MAT.0000000000001699

  View details for Web of Science ID 000894502700019

  View details for PubMedID 35671442

  View details for PubMedCentralID PMC9477972

• Trends, Outcomes, and Predictors of Acute In-hospital Stroke after Lung Transplantation: An Analysis of the United Network for Organ Sharing Database Shou, B. L., Wilcox, C., Krishnan, A., Kim, B. S., Keller, S. P., Whitman, G. J. R., Uchino, K., Bush, E. L., Cho, S. LIPPINCOTT WILLIAMS & WILKINS. 2022: S265

  View details for DOI 10.1097/01.XCS.0000895096.45527.53

  View details for Web of Science ID 000867889300527

• Early Low Pulse Pressure in VA-ECMO Is Associated with Acute Brain Injury NEUROCRITICAL CARE Shou, B. L., Wilcox, C., Florissi, I., Kalra, A., Caturegli, G., Zhang, L. Q., Bush, E., Kim, B., Keller, S. P., Whitman, G. J. R., Cho, S., HERALD Investigators 2023; 38 (3): 612-621

  Abstract

  Pulse pressure is a dynamic marker of cardiovascular function and is often impaired in patients on venoarterial extracorporeal membrane oxygenation (VA-ECMO). Pulsatile blood flow also serves as a regulator of vascular endothelium, and continuous-flow mechanical circulatory support can lead to endothelial dysfunction. We explored the impact of early low pulse pressure on occurrence of acute brain injury (ABI) in VA-ECMO.We conducted a retrospective analysis of adults with VA-ECMO at a tertiary care center between July 2016 and January 2021. Patients underwent standardized multimodal neuromonitoring throughout ECMO support. ABI included intracranial hemorrhage, ischemic stroke, hypoxic ischemic brain injury, cerebral edema, seizure, and brain death. Blood pressures were recorded every 15 min. Low pulse pressure was defined as a median pulse pressure < 20 mm Hg in the first 12 h of ECMO. Multivariable logistic regression was performed to investigate the association between pulse pressure and ABI.We analyzed 5138 blood pressure measurements from 123 (median age 63; 63% male) VA-ECMO patients (54% peripheral; 46% central cannulation), of whom 41 (33%) experienced ABI. Individual ABIs were as follows: ischemic stroke (n = 18, 15%), hypoxic ischemic brain injury (n = 14, 11%), seizure (n = 8, 7%), intracranial hemorrhage (n = 7, 6%), cerebral edema (n = 7, 6%), and brain death (n = 2, 2%). Fifty-eight (47%) patients had low pulse pressure. In a multivariable model adjusting for preselected covariates, including cannulation strategy (central vs. peripheral), lactate on ECMO day 1, and left ventricle venting strategy, low pulse pressure was independently associated with ABI (adjusted odds ratio 2.57, 95% confidence interval 1.05-6.24). In a model with the same covariates, every 10-mm Hg decrease in pulse pressure was associated with 31% increased odds of ABI (95% confidence interval 1.01-1.68). In a sensitivity analysis model adjusting for systolic pressure, pulse pressure remained significantly associated with ABI.Early low pulse pressure (< 20 mm Hg) was associated with ABI in VA-ECMO patients. Low pulse pressure may serve as a marker of ABI risk, which necessitates close neuromonitoring for early detection.

  View details for DOI 10.1007/s12028-022-01607-y

  View details for Web of Science ID 000860383600002

  View details for PubMedID 36167950

  View details for PubMedCentralID PMC10040467

• Pre-operative Machine Learning for Heart Transplant Patients Bridged with Temporary Mechanical Circulatory Support JOURNAL OF CARDIOVASCULAR DEVELOPMENT AND DISEASE Shou, B. L., Chatterjee, D., Russel, J. W., Zhou, A. L., Florissi, I. S., Lewis, T., Verma, A., Benharash, P., Choi, C. 2022; 9 (9)

  Abstract

  Background: Existing prediction models for post-transplant mortality in patients bridged to heart transplantation with temporary mechanical circulatory support (tMCS) perform poorly. A more reliable model would allow clinicians to provide better pre-operative risk assessment and develop more targeted therapies for high-risk patients. Methods: We identified adult patients in the United Network for Organ Sharing database undergoing isolated heart transplantation between 01/2009 and 12/2017 who were supported with tMCS at the time of transplant. We constructed a machine learning model using extreme gradient boosting (XGBoost) with a 70:30 train:test split to predict 1-year post-operative mortality. All pre-transplant variables available in the UNOS database were included to train the model. Shapley Additive Explanations was used to identify and interpret the most important features for XGBoost predictions. Results: A total of 1584 patients were included, with a median age of 56 (interquartile range: 46-62) and 74% male. Actual 1-year mortality was 12.1%. Out of 498 available variables, 43 were selected for the final model. The area under the receiver operator characteristics curve (AUC) for the XGBoost model was 0.71 (95% CI: 0.62-0.78). The most important variables predictive of 1-year mortality included recipient functional status, age, pulmonary capillary wedge pressure (PCWP), cardiac output, ECMO usage, and serum creatinine. Conclusions: An interpretable machine learning model trained on a large clinical database demonstrated good performance in predicting 1-year mortality for patients bridged to heart transplantation with tMCS. Machine learning may be used to enhance clinician judgement in the care of markedly high-risk transplant recipients.

  View details for DOI 10.3390/jcdd9090311

  View details for Web of Science ID 000856397100001

  View details for PubMedID 36135456

  View details for PubMedCentralID PMC9500687

• Temporary Mechanical Circulatory Support for Transcatheter Aortic Valve Replacement JOURNAL OF SURGICAL RESEARCH Shou, B. L., Verma, A., Florissi, I. S., Schena, S., Benharash, P., Choi, C. 2022; 280: 363-370

  Abstract

  This study aimed to characterize the use of temporary mechanical circulatory support (tMCS) among patients undergoing transcatheter aortic valve replacement (TAVR) using a nationally representative database.The 2012-2018 National Inpatient Sample was queried for adult patients who underwent isolated TAVR. The tMCS group was comprised of those who required extracorporeal membrane oxygenation, percutaneous ventricular assist device, or intra-aortic balloon pump during index hospitalization. We evaluated temporal trends in the utilization of tMCS using Cuzick's test. Furthermore, a multivariable logistic regression was used to identify factors associated with tMCS use and its impact on in-hospital mortality, selected complications, and nonhome discharge.Of an estimated 215,925 patients who underwent TAVR, 3085 (1.4%) required tMCS during their hospital course. The most common modality of tMCS was intra-aortic balloon pump (49%), followed by extracorporeal membrane oxygenation (27%) then percutaneous ventricular assist device (18%). Seven percent of tMCS patients were supported by > 1 device. The annual incidence of tMCS usage decreased over the study period, from 3% in 2012 to 1% in 2018 (P-trend < 0.01). Nonelective admission, congestive heart failure, coagulopathy, and liver disease were strong independent predictors of requiring tMCS. Patients requiring tMCS had a 31.8% in-hospital mortality rate (adjusted odds ratio = 23, 95% confidence interval 18.5-28.5), longer length of stay (9 d versus 3, P < 0.001), and higher costs ($84,600 versus $48,100, P < 0.001) than those who did not.The use of tMCS during TAVR has decreased over time but remains associated with a 23-fold increased mortality rate and significant clinical and resource utilization burden.

  View details for DOI 10.1016/j.jss.2022.07.034

  View details for Web of Science ID 000864472000013

  View details for PubMedID 36037613

• Massive left atrial thrombus evades multimodality imaging as a myxoma in a bicaval heart transplant recipient JOURNAL OF CARDIAC SURGERY Shou, B. L., Halub, M. E., Zhou, A. L., Thompkins, B. A., Choi, C. W. 2022; 37 (9): 2884-2887

  Abstract

  Intracardiac masses are an extremely rare and poorly described complication following a bicaval heart transplantation. We describe the case of an asymptomatic 62-year-old male with a large left atrial mass found incidentally on transthoracic echocardiography 6 years post-transplant. A battery of additional imaging tests was ordered including transesophageal echocardiography, 18 F-fluorodeoxyglucose positron emission tomography/computed tomography, and T1 and T2 magnetic resonance imaging. Although imaging biomarkers were generally nonspecific, the mass was most consistent with a cardiac myxoma. However, intraoperative findings confirmed by pathology revealed a massive organizing thrombus. The patient had an uneventful recovery after surgical removal of the mass. Our case highlights a very rare phenomenon in heart transplant recipients which remains a unique diagnostic challenge even with current advances in imaging.

  View details for DOI 10.1111/jocs.16708

  View details for Web of Science ID 000820620200001

  View details for PubMedID 35789119

• Caseous necrosis of the mitral annulus masquerading as an intracardiac mass. Global cardiology science & practice Shou, B. L., Halub, M. E., Zhou, A. L., Lawton, J. S. 2022; 2022 (1-2): e202201

  Abstract

  Caseous necrosis of the mitral annulus is a rare condition which typically involves the posterior leaflet or annulus. We report the case of a 71-year-old female with extensive comorbidities, presenting with dyspnea and angina, who had an incidental echocardiographic finding of a mass on or near the mitral valve. The mass increased in size over the course of three years and was associated with severe mitral regurgitation. The mass was initially thought to be a myxoma, however, surgical exploration revealed caseous necrosis of the posterior mitral annulus. Following removal of the necrotic tissue and distorted mitral leaflet, a bioprosthetic mitral valve was implanted and the patient recovered uneventfully.

  View details for DOI 10.21542/gcsp.2022.1

  View details for PubMedID 36339670

• Relative contributions of sex hormones, sex chromosomes, and gonads to sex differences in tissue gene regulation GENOME RESEARCH Blencowe, M., Chen, X., Zhao, Y., Itoh, Y., McQuillen, C. N., Han, Y., Shou, B. L., McClusky, R., Reue, K., Arnold, A. P., Yang, X. 2022; 32 (5): 807-824

  Abstract

  Sex differences in physiology and disease in mammals result from the effects of three classes of factors that are inherently unequal in males and females: reversible (activational) effects of gonadal hormones, permanent (organizational) effects of gonadal hormones, and cell-autonomous effects of sex chromosomes, as well as genes driven by these classes of factors. Often, these factors act together to cause sex differences in specific phenotypes, but the relative contribution of each and the interactions among them remain unclear. Here, we used the four core genotypes (FCG) mouse model with or without hormone replacement to distinguish the effects of each class of sex-biasing factors on transcriptome regulation in liver and adipose tissues. We found that the activational hormone levels have the strongest influence on gene expression, followed by the organizational gonadal sex effect, and last, sex chromosomal effect, along with interactions among the three factors. Tissue specificity was prominent, with a major impact of estradiol on adipose tissue gene regulation and of testosterone on the liver transcriptome. The networks affected by the three sex-biasing factors include development, immunity and metabolism, and tissue-specific regulators were identified for these networks. Furthermore, the genes affected by individual sex-biasing factors and interactions among factors are associated with human disease traits such as coronary artery disease, diabetes, and inflammatory bowel disease. Our study offers a tissue-specific account of the individual and interactive contributions of major sex-biasing factors to gene regulation that have broad impact on systemic metabolic, endocrine, and immune functions.

  View details for DOI 10.1101/gr.275965.121

  View details for Web of Science ID 000802837300001

  View details for PubMedID 35396276

  View details for PubMedCentralID PMC9104702

• Massive primary cardiac synovial sarcoma of the left atrium: a case report JOURNAL OF CARDIOTHORACIC SURGERY Zhou, A. L., Halub, M. E., Gross, J. M., Shou, B. L., Kilic, A. 2022; 17 (1): 76

  Abstract

  Synovial sarcomas are tumors typically located in the extremities and characterized by a t(X;18)(p11.2;q11.2) chromosomal translocation. With only around 100 cases reported in the literature, cardiac synovial sarcomas are extremely rare.We describe a case of a 59-year-old male who presented to his primary care physician with chest pain, palpitations, and dyspnea and was diagnosed with atrial flutter. Following atrial ablation, a transthoracic echocardiogram incidentally revealed a 5.5 × 5.0 cm heterogeneous mass. Further workup found a heterogeneous mass with mild fluorodeoxyglucose uptake that was abutting the left atrium, left ventricle, and left pulmonary veins. The tumor was resected and confirmed to be a monophasic synovial sarcoma with a SS18-SSX gene fusion. Four months post-operative, the patient had recovered well from surgery. He is currently undergoing concurrent radiation and chemotherapy.Due to the rarity of this tumor, guidelines on diagnosis and treatment come only from case reports. Our case describes a primary cardiac synovial sarcoma arising from the left atrium in the atrioventricular groove in which diagnosis of atrial flutter preceded detection of the mass.

  View details for DOI 10.1186/s13019-022-01822-w

  View details for Web of Science ID 000782602500002

  View details for PubMedID 35422025

  View details for PubMedCentralID PMC9009006

• Impact of the COVID-19 pandemic on patients with paediatric cancer in low-income, middle-income and high-income countries: a multicentre, international, observational cohort study BMJ OPEN Bandyopadhyay, S., Peter, N., Lakhoo, K., Vieira Abib, S., Abdelhafeez, H., Wilson, S., Pachl, M., Martin, B., Nagras, S., Sheth, M., Dominic, C., Gandhi, S., Parwani, D., Raj, R., Munezero, D., Dutta, R., Roseline, N., McClafferty, K., Nazari, A., Sriram, S., Pillarisetti, S., Nweze, K., Ashwinee, A., Kalra, G., Patil, P., Nathani, P., Bhullar, K., Elhadi, M., Khan, M., Rahim, N., Madhusudanan, S., Erhabor, J., Shirke, M., Mughal, A., Au, D., Salehi, M., Royyuru, S., Ahmed, M., Hussain, S., Robinson, D., Casey, A., Khan, M., Dukundane, A., Festus, K., Govind, V., Pancharatnam, R., Ochieng, L., Taylor, E. H., Nautiyal, H., Crespo, M., Charuvil, S., Valetopoulou, A., Ravi, K., Jalloh, F., Badwi, N., Shah, S., Rajpal, R., Rana, M., Qadir, M., Uwiringiyimana, E., Azzam, A., Fanelli, M., Ataide Gomes, G., Buarque, I., Guerini, I., Bouderbala, A., Alfurais, S., Gamal, M., Hijazi, Y., Tailakh, S., Al-Naggar, H., Douba, Z., Elejla, S., Eldaly, A., Sharashi, E., Mansour, A., Elyan, T., Nesrine, A., Ayman, A., Zazo, A., Bonna, M., Lorabi, S., Alalami, H., Emam, R., Bwala, K., Umar, A. M., Aremu, A., Suleiman, D. E., Aliyu, T., Saleem, A., Arshad, M., Turk, K., Altaf, S., Ogunsua, O., Sholadoye, T., Tolani, M., Alfa, Y., Mubarak, K., Irungu, E., Muma, K., Muma, S., Obat, M., Sameh, Y., Qasem, A., Ayasra, F., Alnajjar, R., Abdel-Maboud, M., Bahaa, A., Saadeldin, A. M., Adwi, M., Adly, M., Elshenawy, A., Harky, A., Gentle, L., Wright, K., Luyt, J., White, O., Smith, C., Thompson, N., Smith, T., Harrison, I., Mitul, A., Karim, S., Islam, N., Alsaeiti, S., Benkhial, F., Almihashhish, M., Burzeiza, E., Masoud, H., Alshamikh, M., Nasef, R., Mohammed, F., Lo, W. B., Togarepi, N., Carrolan, E., O'Sullivan, B. J., Hassanin, M., Saleh, A., Bassiony, M., Qatora, M., Bahaaeldin, M., Fadel, S., El Chazli, Y., Hamizi, K., Zekkour, M., Rahmoun, R., Drid, B., Abu Teir, S., Kadir, M., Zerizer, Y., Khernane, N., Saada, B., Ammouze, I., Elkaoune, Y., Moujtahid, H., Chaoui, G., Benaouda, H., Gounni, M., Aji, N., Hessissen, L., Monteiro, J., Nunes, S., do Bom-Sucesso, M., Lal, D. R., Craig, B. T., Becktell, K., Banu, T., Alam, M., Pulock, O., Aziz, T., Ilic, R., Grujicic, D., Nastasovic, T., Lazic, I., Milicevic, M., Bascarevic, V., Mijalcic, R., Scepanovic, V., Stanimirovic, A., Islam, S., Basher, A., Akter, M., Rahman, S., Ara, Z., Ahammed, M., Akter, T., Nahar, K., Sayed, F., Saracoglu, K., Akova, E., Aydogmus, E., Kendirlioglu, B., Hicdonmez, T., Adhnon, A., Rana, A., Humad, H., Madasu, A., Azzam, A. Y., Azab, M. A., Ghozy, S., Salah, A., Moses, O., Taibat, I., Jones, T., Ukoha, K., Goke, O., Ikechukwu, O., Idowu, A., Chitnis, M., Nauhaus, H., Erwee, D., Brown, R., Chylinska, A., Simpson, R., Gomes, P., Ciriaco Padilha, M., de Oliveira Junior, E., de Carvalho, L., Diz, F., El Kassas, M., Eldaly, U., Tawheed, A., Abdelwahab, M., Yassaad, O., Hajar, B., Abdessamad, E., Yasser, A., Laila, H., Yahya, F., Al-Agele, Y., Gallardo, M., Vasquez, J., Leon, J., Yip, S., Lami, M., Byrne, M. H., Jasim, D., Ghattaura, H., Etchill, E. W., Rhee, D., Cooper, S., Crow, K., Drucker, M., Murphy, M., Shou, B., Siegel, A., Kara, Y., Ozdemir, G., Elfiky, M., Refaee, E., Massoud, J., Ibrahim, A., Ibrahim, R., Abu Za'nouneh, F., Baddourah, R. M., Fahmawee, T., Al-Shraideh, A., Salman, G., Alameer, E., Ali, A., Yahia, G., Waleed, K., Abou Chaar, M. K., Sultan, I., Ghandour, K., Al-Dabaibeh, S., Al-Basiti, A., Ababneh, H., El-Qurneh, O., Alalawi, Y., Al Ayed, A., Hanafy, E., Bolowi, N., Loh, A. H. P., Jacobsen, A. S., Barola, H., Pagaduan, A. L., Fan, J., Elebute, O., Ademuyiwa, A. O., Bode, C. O., Seyi-Olajide, J. O., Ladipo-Ajayi, O., Alakaloko, F. M., Ihediwa, G. C., Temiye, E. O., Zarrish, J., Saleem, R., Zahid, S., Amirali, A., Nadeem, A., Tebha, S., Qayyum, Z., Tahir, S., Tahir, A., Qureshi, T., Kumari, P., Calvagna, V., Galea, N., Axiaq, A., Schuelke, M. R., Kloeber, J. A., Owen, R. L., Roth, A. S., Yang, C., Barnett, J., Jay, L. P., Wyatt, K., Medical, P., Vojcek, A., Alrahawy, M., Ragab, S. M., Allam, A. R., Hager, E., Sakar, M., Cakmak, G., Sallam, I., Amira, G., Sherief, M., Sherif, A., Coelho, S., Ikeda, A., Portela, L., Garrigo, M., de Carvalho, R., Lobo, F., Ferman, S., Lima, F., Elhassan, M., Elhaj, N., Hamid, H. K. S., Ameh, E. A., Nwatah, V. E., Nnamdi, A., Osuigwe, A., Ekwunife, O., Nri-Ezedi, C., Umeh, E., Bell, N., Ogundele, I., Adekanmbi, A., Fatungase, O., Obafemi, O., Al-Furais, S., Hemlae, H., Nay, S., Mathew, J., de Moraes Costa Carlesse, F., Fanelli, M., Kelly, F., Lapolla, P., Mingoli, A., Cozzi, D., Testi, A., Musiu, P., Sapienza, P., Brachini, G., Zambon, M., Meneghini, S., Abdenour, A., Souad, B., Malika, M., Belkacem, B., Meelad, A., Salim, H., Haider, F., Al Fayez, F., Rahim, F., Abdul-Mumin, A., Fuseini, H., Kwarteng, P., Abdulai, A., Kunfah, S., Bonsaana, G. B., Ajinkpang, S., Der, E. M., Abantanga, F. A., Elbahnasawy, M., Abdelsalam, S., Samir, A., Baertschiger, R. M., Brar, A., Matei, A. C., Zani, A., Samad, L., Zuberi, H., Nadeem, K., Khayyam, N., Imran, F., Zia, N., Muhammad, S., Raza, M., Khan, M., Hamdan, A., Omran, A., Moussa, A., Gawrieh, B., Salloum, H., Ahmed, A., Mazloum, A., Abodest, A., Ali, N., Bouhuwaish, A., Abdulkarim, A., Abdulwahed, E., Biala, M., Ghamgh, R., Alamre, A., Shelft, M., Albanna, A. A. M., Tawel, H., Hatzipantelis, E., Tragiannidis, A., Tsotridou, E., Galli-Tsinopoulou, A., Aziz, D., Latiff, Z., Alias, H., Loh, C., Lau, D., Zaman, A., Vuille-dit-Bille, R. N., Holland-Cunz, S. G., Allafi, N., Lawal, T., Egbuchulem, K., Ogundoyin, O., Olulana, I., Brown, B. J., Afolaranmi, O., Fehintola, A., Heuer, A., Nitschke, C., Boettcher, M., Priemel, M., Viezens, L., Stangenberg, M., Dreimann, M., Reiter, A., Meyer, J., Olori, S., Offiong, U., Mshelbwala, P., Patrick, F., Umar, A., ThankGod, O., Nasir, A. A., Ibrahim, K. O. O., Ademola-Popoola, D. S., Sayomi, O. T., Abdurrzzaq, A., Adeyeye, A. A., Omokanye, K. O., Abdur-Rahman, L. O., Bamidele, O., Nah, S., Ng, Y., Zubaidi, S., Almasri, M., Ali, S., Olaosebikan, R., Muthukumar, A., Shinondo, P., Ngongola, A., Bvulani, B., Patel, A., Nuhu-Koko, A., Jibrin, B., Olalekan, A. L., Lukong, C. S., Vall, E., Guillen, G., Lopez, S., Molino, J., Velasco, P., Elmandouh, O., Hamam, O., Elmandouh, R., Ruzgar, N., Levinson, R., Kala, S., Ullrich, S., Christison-Lagay, E., Mortada, A., Ebada, M., Solimam, E., Abualkher, K., Yousf, A., Holail, M., Mohamed, R., Ismail, R., Kpiniong, M., Hattor, K., Bimpong, K., Global Hlth Res Grp Childrens Non- 2022; 12 (4): e054690

  Abstract

  Paediatric cancer is a leading cause of death for children. Children in low-income and middle-income countries (LMICs) were four times more likely to die than children in high-income countries (HICs). This study aimed to test the hypothesis that the COVID-19 pandemic had affected the delivery of healthcare services worldwide, and exacerbated the disparity in paediatric cancer outcomes between LMICs and HICs.A multicentre, international, collaborative cohort study.91 hospitals and cancer centres in 39 countries providing cancer treatment to paediatric patients between March and December 2020.Patients were included if they were under the age of 18 years, and newly diagnosed with or undergoing active cancer treatment for Acute lymphoblastic leukaemia, non-Hodgkin's lymphoma, Hodgkin lymphoma, Wilms' tumour, sarcoma, retinoblastoma, gliomas, medulloblastomas or neuroblastomas, in keeping with the WHO Global Initiative for Childhood Cancer.All-cause mortality at 30 days and 90 days.1660 patients were recruited. 219 children had changes to their treatment due to the pandemic. Patients in LMICs were primarily affected (n=182/219, 83.1%). Relative to patients with paediatric cancer in HICs, patients with paediatric cancer in LMICs had 12.1 (95% CI 2.93 to 50.3) and 7.9 (95% CI 3.2 to 19.7) times the odds of death at 30 days and 90 days, respectively, after presentation during the COVID-19 pandemic (p<0.001). After adjusting for confounders, patients with paediatric cancer in LMICs had 15.6 (95% CI 3.7 to 65.8) times the odds of death at 30 days (p<0.001).The COVID-19 pandemic has affected paediatric oncology service provision. It has disproportionately affected patients in LMICs, highlighting and compounding existing disparities in healthcare systems globally that need addressing urgently. However, many patients with paediatric cancer continued to receive their normal standard of care. This speaks to the adaptability and resilience of healthcare systems and healthcare workers globally.

  View details for DOI 10.1136/bmjopen-2021-054690

  View details for Web of Science ID 000789493400010

  View details for PubMedID 35410925

  View details for PubMedCentralID PMC9021459

• Pulmonary artery transection for resection of a middle mediastinal paraganglioma CLINICAL CASE REPORTS Zhou, A. L., Halub, M. E., Lotfalla, M., Shou, B. L., Kilic, A. 2022; 10 (4): e05600

  Abstract

  We report the case of a 65-year-old male patient who presented with chest pain and was found to have a mediastinal paraganglioma between the left atrium and main pulmonary artery. This is the first reported case of a mediastinal paraganglioma resection utilization transection of the main pulmonary artery.

  View details for DOI 10.1002/ccr3.5600

  View details for Web of Science ID 000779382200001

  View details for PubMedID 35425604

  View details for PubMedCentralID PMC8991763

• Mild hypothermia and neurologic outcomes in patients undergoing venoarterial extracorporeal membrane oxygenation JOURNAL OF CARDIAC SURGERY Al-Kawaz, M., Shou, B., Prokupets, R., Whitman, G., Geocadin, R., Cho, S. 2022; 37 (4): 825-830

  Abstract

  Patients with venoarterial extracorporeal membrane oxygenation (VA-ECMO) are at risk of cerebral reperfusion injury after prolonged hypoperfusion and immediate restoration of systemic blood flow. We aimed to examine the impact of mild hypothermia during the first 24 h post-ECMO on neurological outcomes in VA-ECMO patients.This was a retrospective study of adult VA-ECMO patients from a tertiary care center. Mild hypothermia was defined as 32-36°C during the first 24 h post-ECMO. The primary outcome was a good neurological function at discharge measured by a modified Rankin Scale ≤3. Multivariable logistic regression analysis was performed for primary outcome adjusting for pre-specified covariates.Overall, 128 consecutive patients with VA-ECMO support (median age: 60 years and 63% males) were included. Within the first 24 h of VA-ECMO cannulation, we found a median of 71 readings per patient (interquartile range 45-88). Eighty-eight patients (68.8%) experienced mild hypothermia within the first 24 h while 18 of those 88 patients (14.2%) had a mean temperature <36°C. ECMO indications included post-cardiotomy shock (39.8%), cardiac arrest (29.7%), and cardiogenic shock (26.6%). Duration of mild hypothermia, but not mean temperature, was independently associated with increased odds of good neurological outcome at discharge (odds ratio [OR] = 1.16, 95% confidence interval [CI] = 1.04-1.31, p = .01) after adjusting for age, the severity of illness, post-ECMO systemic hemorrhage, post-cardiotomy shock, acute brain injury, and mean 24-h PaO2 . Neither duration of mild hypothermia (OR = 0.93, CI = 0.84-1.03, p = .17) nor mean temperature (OR = 0.78, CI = 0.29-2.08, p = .62) was significantly associated with mortality. Similarly, duration of mild hypothermia (p = .47) and mean 24-h temperature (p = .76) were not significantly associated with the frequency of systemic hemorrhages.In this single-center study, a longer duration of mild hypothermia during the first 24 h of ECMO support was significantly associated with improved neurological outcomes. Mild hypothermia was not associated with an increased risk of systemic hemorrhage or improved survival.

  View details for DOI 10.1111/jocs.16308

  View details for Web of Science ID 000754393200001

  View details for PubMedID 35152478

  View details for PubMedCentralID PMC8891050

• Machine learning from quantitative coronary computed tomography angiography predicts ischemia and impaired myocardial blood flow Lin, A., Van Diemen, P., Motwani, M., McElhinney, P., Otaki, Y., Han, D., Kwan, A., Tzolos, E., Cadet, S., Danad, I., Driessen, R., Slomka, P. J., Berman, D. S., Dey, D., Knaapen, P. OXFORD UNIV PRESS. 2021: 206

  View details for Web of Science ID 000720456900161

• Systematic evaluation of transcriptomics-based deconvolution methods and references using thousands of clinical samples BRIEFINGS IN BIOINFORMATICS Nadel, B. B., Oliva, M., Shou, B. L., Mitchell, K., Ma, F., Montoya, D. J., Mouton, A., Kim-Hellmuth, S., Stranger, B. E., Pellegrini, M., Mangul, S. 2021; 22 (6)

  Abstract

  Estimating cell type composition of blood and tissue samples is a biological challenge relevant in both laboratory studies and clinical care. In recent years, a number of computational tools have been developed to estimate cell type abundance using gene expression data. Although these tools use a variety of approaches, they all leverage expression profiles from purified cell types to evaluate the cell type composition within samples. In this study, we compare 12 cell type quantification tools and evaluate their performance while using each of 10 separate reference profiles. Specifically, we have run each tool on over 4000 samples with known cell type proportions, spanning both immune and stromal cell types. A total of 12 of these represent in vitro synthetic mixtures and 300 represent in silico synthetic mixtures prepared using single-cell data. A final 3728 clinical samples have been collected from the Framingham cohort, for which cell populations have been quantified using electrical impedance cell counting. When tools are applied to the Framingham dataset, the tool Estimating the Proportions of Immune and Cancer cells (EPIC) produces the highest correlation, whereas Gene Expression Deconvolution Interactive Tool (GEDIT) produces the lowest error. The best tool for other datasets is varied, but CIBERSORT and GEDIT most consistently produce accurate results. We find that optimal reference depends on the tool used, and report suggested references to be used with each tool. Most tools return results within minutes, but on large datasets runtimes for CIBERSORT can exceed hours or even days. We conclude that deconvolution methods are capable of returning high-quality results, but that proper reference selection is critical.

  View details for DOI 10.1093/bib/bbab265

  View details for Web of Science ID 000733325700135

  View details for PubMedID 34346485

  View details for PubMedCentralID PMC8768458

• MACHINE LEARNING ISCHEMIA RISK SCORE FROM CORONARY CT ANGIOGRAPHY PREDICTS LESION-SPECIFIC ISCHEMIA AND IMPAIRED MYOCARDIAL BLOOD FLOW: RESULTS FROM THE PACIFIC TRIAL Lin, A., Van Diemen, P., Motwani, M., McElhinney, P., Otaki, Y., Kwan, A., Han, D., Kuronuma, K., Klein, E., Grodecki, K., Shou, B., Cadet, S., Danad, I., Driessen, R., Slomka, P., Berman, D., Dey, D., Knaapen, P. ELSEVIER SCIENCE INC. 2021: 1269

  View details for Web of Science ID 000647487501277