Transplantation Outcomes with Donor Hearts after Circulatory Death.

BACKGROUND: Data showing the efficacy and safety of the transplantation of hearts obtained from donors after circulatory death as compared with hearts obtained from donors after brain death are limited. METHODS: We conducted a randomized, noninferiority trial in which adult candidates for heart transplantation were assigned in a 3:1 ratio to receive a heart after the circulatory death of the donor or a heart from a donor after brain death if that heart was available first (circulatory-death group) or to receive only a heart that had been preserved with the use of traditional cold storage after the brain death of the donor (brain-death group). The primary end point was the risk-adjusted survival at 6 months in the as-treated circulatory-death group as compared with the brain-death group. The primary safety end point was serious adverse events associated with the heart graft at 30 days after transplantation. RESULTS: A total of 180 patients underwent transplantation; 90 (assigned to the circulatory-death group) received a heart donated after circulatory death and 90 (regardless of group assignment) received a heart donated after brain death. A total of 166 transplant recipients were included in the as-treated primary analysis (80 who received a heart from a circulatory-death donor and 86 who received a heart from a brain-death donor). The risk-adjusted 6-month survival in the as-treated population was 94% (95% confidence interval [CI], 88 to 99) among recipients of a heart from a circulatory-death donor, as compared with 90% (95% CI, 84 to 97) among recipients of a heart from a brain-death donor (least-squares mean difference, -3 percentage points; 90% CI, -10 to 3; P<0.001 for noninferiority [margin, 20 percentage points]). There were no substantial between-group differences in the mean per-patient number of serious adverse events associated with the heart graft at 30 days after transplantation. CONCLUSIONS: In this trial, risk-adjusted survival at 6 months after transplantation with a donor heart that had been reanimated and assessed with the use of extracorporeal nonischemic perfusion after circulatory death was not inferior to that after standard-care transplantation with a donor heart that had been preserved with the use of cold storage after brain death. (Funded by TransMedics; ClinicalTrials.gov number, NCT03831048.).

Applying the antecedent, behaviour, and consequence taxonomy to unintentional firearm injury as determined by a collaborative firearm injury database.

BACKGROUND: Unintentional firearm injury (UFI) remains a significant problem in the USA with respect to preventable injury and death. The antecedent, behaviour and consequence (ABC) taxonomy has been used by law enforcement agencies to evaluate unintentional firearm discharge. Using an adapted ABC taxonomy, we sought to categorise civilian UFI in our community to identify modifiable behaviours. METHODS: Using a collaborative firearm injury database (containing both a university-based level 1 trauma registry and a metropolitan law enforcement database), all UFIs from August 2008 through December 2021 were identified. Perceived threat (antecedent), behaviour and injured party (consequence) were identified for each incident. RESULTS: During the study period, 937 incidents of UFI were identified with 64.2% of incidents occurring during routine firearm tasks. 30.4% of UFI occurred during neglectful firearm behaviour such as inappropriate storage. Most injuries occurred under situations of low perceived threat. UFI involving children was most often due to inappropriate storage of weapons, while cleaning a firearm was the most common behaviour in adults. Overall, 16.5% of UFI involved injury to persons other than the one handling the weapon and approximately 1.3% of UFI resulted in mortality. CONCLUSIONS: The majority of UFI occurred during routine and expected firearm tasks such as firearm cleaning. Prevention programmes should not overlook these modifiable behaviours in an effort to reduce UFIs, complications and deaths.

Structural racism: A concept analysis.

BACKGROUND: Despite the broad agreement that structural racism is problematic, there remains significant confusion as to what structural racism means and how to research it. PURPOSE: Perform a comprehensive concept analysis of structural racism and propose an operational definition. METHODS: Walker and Avant's eight-step, iterative method was used for conducting the concept analysis. DISCUSSION: Structural racism has five defining attributes: oppressive racial ideologies, dynamic state, inverse-related influence, temporality, and a false sense of "racial equity." Structural racism has six antecedents: explicit racial bias, implicit racial bias, racial discrimination, institutional racism, cultural racism, and systemic racism. There are three consequences of structural racism: group categorization, unequal treatment, and racial inequities. CONCLUSION: To combat and defeat the historical and ongoing impact of structural racism, conceptual clarity must be established. Only then can an operational definition be proposed and instruments developed that correspond with the nature of structural racism.

Plasma resuscitation improves and restores intestinal microcirculatory physiology following haemorrhagic shock.

BACKGROUND AND OBJECTIVES: Intestinal ischaemia-reperfusion injury following resuscitated haemorrhagic shock (HS) leads to endothelial and microcirculatory dysfunction and intestinal barrier breakdown. Although vascular smooth muscle machinery remains intact, microvascular vasoconstriction occurs secondary to endothelial cell dysfunction, resulting in further ischaemia and organ injury. Resuscitation with fresh frozen plasma (FFP) improves blood flow, stabilizes the endothelial glycocalyx and alleviates organ injury. We postulate these improvements correlate with decreased tissue CO2 concentrations, improved microvascular oxygenation and attenuation of intestinal microvascular endothelial dysfunction. MATERIALS AND METHODS: Male Sprague-Dawley rats were randomly assigned to groups (n = 8/group): (1) sham, (2) HS (40% mean arterial blood pressure [MAP], 60 min) + crystalloid resuscitation (CR) (shed blood saline) and (3) HS + FFP (shed blood + FFP). MAP, heart rate (HR), ileal perfusion, pO2 and pCO2 were measured at intervals until 4 h post-resuscitation (post-RES). At 4 h post-RES, the ileum was rinsed in situ with Krebs solution. Topical acetylcholine and then nitroprusside were applied for 10 min each. Serum was obtained, and after euthanasia, tissues were harvested and snap-frozen in liquid N2 and stored at -80°C. RESULTS: FFP resuscitation resulted in sustained ileal perfusion as well as rapid sustained return to baseline microvascular pO2 and pCO2 values when compared to CR (p < 0.05). Endothelial function was preserved relative to sham in the FFP group but not in the CR group (p < 0.05). CONCLUSION: FFP-based resuscitation improves intestinal perfusion immediately following resuscitation, which correlates with improved tissue oxygenation and decreased tissue CO2 levels. CR resulted in significant damage to endothelial vasodilation response to acetylcholine, while FFP preserved this function.

The influence of polygraphs on evaluators' decisions regarding sexually violent persons.

OBJECTIVE: This study examined the degree to which polygraph results affected evaluators' decisions regarding patients committed as sexually violent persons (SVPs) in Wisconsin. Specifically, we examined evaluators' opinions on patients' significant progress in treatment (SPT), suitability for supervised release, and suitability for discharge. HYPOTHESES: We hypothesized that having failed a polygraph during the prior year would predict evaluators' opinions that patients did not meet criteria for SPT, supervised release, and discharge from civil commitment even after analyses controlled for other factors related to evaluators' decision making. Similarly, we hypothesized that patients taking and passing polygraphs in the year before the evaluations would predict positive recommendations for the aforementioned outcomes. METHOD: All patients civilly committed under Wisconsin's SVP statute who had a Treatment Progress Report (TPR) and a Chapter 980.07 evaluation completed by a state-employed forensic evaluator in 2017 were eligible for this study; we selected a random sample of 158 participants. TPR and 980.07 evaluation reports were coded to reflect evaluators' opinions regarding SPT, supervised release, and/or discharge. All polygraph types and outcomes completed within the review period were coded. RESULTS: Results indicated that taking and passing polygraphs significantly predicted favorable evaluator opinions regarding SPT after analyses controlled for other potentially relevant factors. Polygraphs were not significantly predictive of discharge or supervised release recommendations after analyses controlled for other factors. CONCLUSIONS: Some polygraph outcomes may affect specific evaluator opinions regarding treatment progress. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Unconventional use of total artificial heart in a patient with severe, destructive prosthetic valve endocarditis.

Here, we report the case of a patient who presented to our institution with severe, destructive, and unreconstructable prosthetic valve endocarditis which required the planned implantation of a total artificial heart (TAH) to function as a bridge to cardiac transplantation. The use of TAH in this fashion has been infrequently reported in the literature. This case highlights the importance of a thoughtful, preoperative multidisciplinary approach to these complex patients to provide the most appropriate and life-saving care.

Risk factors and outcomes for delayed kidney graft function in simultaneous heart and kidney transplant recipients: A UNOS/OPTN database analysis.

There are no prior studies assessing the risk factors and outcomes for kidney delayed graft function (K-DGF) in simultaneous heart and kidney (SHK) transplant recipients. Using the OPTN/UNOS database, we sought to identify risk factors associated with the development of K-DGF in this unique population, as well as outcomes associated with K-DGF. A total of 1161 SHK transplanted between 1998 and 2018 were included in the analysis, of which 311 (27%) were in the K-DGF (+) group and 850 in the K-DGF (-) group. In the multivariable analysis, history of pretransplant dialysis (OR: 3.95; 95% CI: 2.94 to 5.29; p < .001) was significantly associated with the development of K-DGF, as was donor death from cerebrovascular accident and longer cold ischemia time of either organ. SHK recipients with K-DGF had increased mortality (HR: 1.99; 95% CI: 1.52 to 2.60; p < .001) and death censored kidney graft failure (HR: 3.51; 95% CI: 2.29 to 5.36; p < .001) in the multivariable analysis. Similar outcomes were obtained when limiting our study to 2008-2018. Similar to kidney-only recipients, K-DGF in SHK recipients is associated with worse outcomes. Careful matching of recipients and donors, as well as peri-operative management, may help reduce the risk of K-DGF and the associated detrimental effects.

Survival after orthotopic heart transplantation in patients with BMI > = 35 with and without diabetes.

BACKGROUND: Orthotopic heart transplant (OHT) recipients with a body mass index (BMI) > = 35 have worse survival than those with a BMI < 35. Diabetes is a risk factor for mortality. We evaluated the impact of diabetes on mortality rates after OHT in patients with a BMI > 35. METHODS: Patients > 18 years who underwent OHT 2008-2017 with a BMI > = 35 were identified in the United Network for Organ Sharing (UNOS) database. Recipient and donor characteristics were compared. A Kaplan Meier analysis was performed. A multivariable Cox proportional hazards model examined the relationship between diabetes and survival. The equivalence of survival outcomes was examined by an unadjusted Cox proportional hazards model and the two one-sided test procedure, using a pre-specified equivalence region. RESULTS: Patients with diabetes were older, had a higher creatinine, lower bilirubin, fewer months on the waitlist, and the donor was less likely to be on inotropes. Kaplan-Meier analysis showed no difference in patient survival. Recipient factors associated with an increased risk of death were increasing bilirubin and machine ventilation. Increasing ischemic time resulted in an increased hazard of death. Long-term survival outcomes were equivalent. CONCLUSIONS: In OHT recipients with a BMI > 35, there is no statistical difference in longterm survival in recipients with or without diabetes. These results encourage continued consideration for OHT in patients BMI > 35 with coexisting diabetes.

Amiodarone Use Prior to Cardiac Transplant Impacts Early Post-Transplant Survival.

PURPOSE: It remains unclear if use of amiodarone pre-cardiac transplantation impacts early post-transplant survival. METHODS: We selected all patients undergoing heart transplant from 2004 to 2006 with available information using the United Network for Organ Sharing database (n = 4057). Multivariable Cox models compared the risk of death within 30 days post-transplant in patients who were taking amiodarone at the time of transplant listing (n = 1227) to those who were not (n = 2830). RESULTS: Mean age was 52 (± 12) years, and 23% were women. Patients who died within 30 days (n = 168) were older; had higher panel reactive antibody levels, higher bilirubin levels, and higher prevalence of prior cardiac surgery; were often at status 1B; and had higher use of amiodarone at listing compared to those who survived (5.3% versus 3.6%; p = 0.02). Cause of death was unknown in 49% and was reported as graft failure in 43% of cases. In multivariable Cox models, patients on amiodarone at the time of listing had 1.56-fold higher risk of post-transplant death within 30 days (95% confidence intervals 1.08-2.27) compared to patients who were not on amiodarone at listing (C-statistic 0.70). CONCLUSION: In conclusion, patients who reported taking amiodarone at the time of listing for transplant had a higher risk of death within 30 days post-transplant.

Left ventricular assist device implantation by bi-thoracotomy technique: A single-center perspective.

BACKGROUND: Left ventricular assist devices (LVAD) are standardly implanted via full sternotomy. Nonsternotomy approaches are gaining popularity, but potential benefits of this approach have not been well-studied. We hypothesized that LVAD implantation by bi-thoracotomy (BT) would demonstrate smaller and more consistent inflow cannula angles leading to improved postoperative outcomes compared to sternotomy. METHODS: Charts of patients who underwent LVAD implantation between June 2018 and June 2020 at a single academic institution were retrospectively reviewed. Patient demographics, surgical approach (sternotomy vs. BT), laboratory values, and postoperative course were compared. The inflow cannula angle was measured on the first chest radiograph available postoperatively. RESULTS: Of 40 patients studied, BT approach was used in 17 (42.5%). Mean inflow cannula angles were smaller in BT patients (23.0 vs. 37.1 degrees, p = .018) and had a smaller standard deviation (13.8 vs. 20.3). Excluding patients who went on to receive a heart transplant or died in the same hospitalization, there was no difference in median length of hospital stay after surgery (16.0 vs. 17.5 days, p = .768). However, BT patients required fewer days of postoperative inotrope support (4.0 vs. 7.0 days, p = .012). CONCLUSIONS: Our data suggest inflow cannula angles are smaller and more consistent with the BT approach, which leads to a shorter duration of postoperative inotropic support. This finding may suggest improved right heart function following LVAD implant via BT approach. Further study is warranted to determine additional benefits of the BT approach.

Successful heart transplantation in a patient who recovered from COVID-19.

Coronavirus disease-2019 has created unprecedented challenges for society, and specifically the medical community. While the pandemic continues to unfold, the transplant community has had to pivot to keep recipients, donors, and institutional transplant teams safe given the unique circumstances inherent to solid organ transplantation.

Long-term discontinuation of warfarin in a patient with HeartMate 3 left ventricular assist device without complication.

A 38-year-old woman with peripartum cardiomyopathy underwent placement of a HeartMate 3 (HM3) left ventricular assist device (LVAD). Postoperatively, she refused warfarin therapy and was maintained on aspirin monotherapy for 19 months. She did not experience thrombotic or thromboembolic complications associated with lack of oral vitamin K antagonist anticoagulation. Our patient represents the longest reported duration of a patient with HM3 LVAD maintained without warfarin without evidence of thrombotic or thromboembolic events.

Direct peritoneal resuscitation reduces inflammation in the kidney after acute brain death.

Brain death is associated with significant inflammation within the kidneys, which may contribute to reduced graft survival. Direct peritoneal resuscitation (DPR) has been shown to reduce systemic inflammation after brain death. To determine its effects, brain dead rats were resuscitated with normal saline (targeted intravenous fluid) to maintain a mean arterial pressure of 80 mmHg; DPR animals also received 30 cc of intraperitoneal peritoneal dialysis solution. Rats were euthanized at 0, 2, 4, and 6 h after brain death. Pro-inflammatory cytokines were measured using ELISA. Levels of IL-1ß, TNF-α, and IL-6 in the kidney were significantly increased as early as 2 h after brain death and significantly decreased with DPR. Levels of leukocyte adhesion molecules ICAM and VCAM increased after brain death and were decreased with DPR (ICAM 2.33 ± 0.14 vs. 0.42 ± 0.04, P = 0.002; VCAM 82.6 ± 5.8 vs. 37.3 ± 1.9, P = 0.002 at 4 h) as were E-selectin and P-selectin (E-selectin 25,605 vs. 16,144, P = 0.005; P-selectin 82.5 ± 3.3 vs. 71.0 ± 2.3, P = 0.009 at 4 h). Use of DPR reduces inflammation and adhesion molecule expression in the kidneys, and is associated with reduced macrophages and neutrophils on immunohistochemistry. Using DPR in brain dead donors has the potential to reduce the immunologic activity of transplanted kidneys and could improve graft survival.

Damage-associated molecular patterns in resuscitated hemorrhagic shock are mitigated by peritoneal fluid administration.

Conventional resuscitation (CR) of hemorrhagic shock (HS), a significant cause of trauma mortality, is intravenous blood and fluids. CR restores central hemodynamics, but vital organ flow can drop, causing hypoperfusion, hypoxia, damage-associated molecular patterns (DAMPs), and remote organ dysfunction (i.e., lung). CR plus direct peritoneal resuscitation (DPR) prevents intestinal and hepatic hypoperfusion. We hypothesized that DPR prevents lung injury in HS/CR by altering DAMPs. Anesthetized male Sprague-Dawley rats were randomized to groups ( n = 8/group) in one of two sets: 1) sham (no HS, CR, or DPR), 2) HS/CR (HS = 40% mean arterial pressure (MAP) for 60 min, CR = shed blood + 2 volumes normal saline), or 3) HS/CR + DPR. The first set underwent whole lung blood flow by colorimetric microspheres. The second set underwent tissue collection for Luminex, ELISAs, and histopathology. Lipopolysaccharide (LPS) and DAMPs were measured in serum and/or lung, including cytokines, hyaluronic acid (HA), high-mobility group box 1 (HMGB1), Toll-like receptor 4 (TLR4), myeloid differentiation primary response 88 protein (MYD88), and TIR-domain-containing adapter-inducing interferon-ß (TRIF). Statistics were by ANOVA and Tukey-Kramer test with a priori P < 0.05. HS/CR increased serum LPS, HA, HMGB1, and some cytokines [interleukin (IL)-1α, IL-1ß, IL-6, and interferon-γ]. Lung TLR4 and MYD88 were increased but not TRIF compared with Shams. HS/CR + DPR decreased LPS, HA, cytokines, HMGB1, TLR4, and MYD88 levels but did not alter TRIF compared with HS/CR. The data suggest that gut-derived DAMPs can be modulated by adjunctive DPR to prevent activation of lung TLR-4-mediated processes. Also, DPR improved lung blood flow and reduced lung tissue injury. Adjunctive DPR in HS/CR potentially improves morbidity and mortality by downregulating the systemic DAMP response.

Cell-specific regulation of iNOS by AMP-activated protein kinase in primary rat hepatocytes.

BACKGROUND: AMP-activated protein kinase (AMPK) regulates several metabolic pathways in hepatocytes that are critical to the hepatic response to sepsis and shock. Induction of nitric oxide synthesis is an important response to sepsis, inflammation and shock and many of the stimuli that upregulate inducible nitric oxide synthase (iNOS) also activate AMPK. AMPK inhibits nitric oxide (NO) production in skeletal and cardiac muscle cells, but the role of AMPK in regulating iNOS expression in hepatocytes has not been determined. MATERIALS AND METHODS: Primary cultured rat hepatocytes were preincubated with an AMPK inhibitor, AMPK activators, or transfected with AMPK siRNA before being treated with the proinflammatory cytokines interleukin-1ß (IL-1ß) and interferon-γ (IFNγ). The hepatocyte cell lysate and culture supernatants were collected for Western blot analysis and Griess assay. RESULTS: IL-1ß and IFNγ markedly upregulated iNOS expression and AMPK phosphorylation. IL-1ß + IFNγ-induced NO production and iNOS expression were significantly decreased in hepatocytes treated with the AMPK inhibitor compound C and AMPK knockdown by AMPK siRNA. Cytokine-induced iNOS expression was increased by AMPK activators 1-oxo-2-(2H-pyrrolium-1-yl)-1H-inden-3-olate, AMPK signaling activator III and AICA-riboside. Compound C upregulated Akt and c-Jun N-terminal kinase phosphorylation but decreased IκBα phosphorylation. AICA-riboside exerted opposite effects on these signaling pathways in hepatocytes. CONCLUSIONS: In contrast to other cell types, AMPK increased IL-1ß + IFNγ-induced NO production and iNOS expression through the Akt, c-Jun N-terminal kinase, and NF-κΒ signaling pathways in primary hepatocytes. These data suggest that AMPK-altering medications used clinically may have subsequent effects on iNOS expression and proinflammatory signaling pathways.

Successful Repair of Acute Type A Aortic Dissection 15 Years Following Bilateral Lung Transplantation.

This report describes a patient treated for acute type A aortic dissection 15 years after undergoing bilateral lung transplantation by a clamshell thoracotomy.

Late Surgical Bleeding Following Total Artificial Heart Implantation.

INTRODUCTION: Mechanical circulatory support for heart failure, including the Total Artificial Heart (TAH, Syncardia, Tucson, AZ, USA) has increased in recent years. This report describes bleeding complications associated with the device. METHODS: A single institution prospectively maintained quality improvement database was reviewed encompassing the first year of clinical experience with the TAH. Patients who underwent TAH implantation were identified, and a review of complications and outcomes was undertaken. RESULTS: Ten patients underwent TAH implant. Four patients experienced delayed postoperative bleeding. In three patients the manifestation of bleeding was tamponade and evidenced by TAH decreased cardiac output. In two patients, at postoperative days 31 and 137, there was a partial disruption of the aortic anastomosis along the outer curvature with pseudoaneurysm formation. Both were repaired by primary suture closure, without use of cardiopulmonary bypass. There was no mortality attributable to bleeding. CONCLUSIONS: TAH patients are at risk for delayed postoperative bleeding, often manifest as an acute decrease in cardiac output. Due to pulsatility and high dP/dT, bleeding from the aortic anastomosis should be considered in the differential of a patient with low flow and/or tamponade.

Not So Vats: How Early Is Too Early in the Operative Management of Patients with Traumatic Hemothorax?

BACKGROUND: Video-assisted thoracoscopic surgery (VATS) is a practical resource in the management of traumatic hemothorax. However, it carries inherent risks and should be mobilized cost-effectively. In this study, we investigated the ideal VATS timing using cost analysis. METHODS: 617 cases of unilateral traumatic hemothorax from 2012 to 2022 were identified in our trauma database. We extracted encounter cost, length of stay (LOS), and operative cost information. Using Kruskal-Walli's test, we compared the cost and LOS for patients who underwent VATS or continued nonoperative management in the first 7 days of admission. Additionally, we computed the daily proportion of patients initially managed nonoperatively but ultimately underwent VATS. P-values <.05 were considered significant. RESULTS: The median encounter cost of cases managed operatively before hospital day 4 (HD4) was higher than those managed nonoperatively. This difference was $63k on HD2 (P-value .07) and was statistically significant for HD3 (difference of $65k, P-value .02). The median LOS with operational management on HD2 and 3 was 7 and 6 respectively vs median LOS of 2 and 3 with nonoperative management on those days (P-value <.001, .01 respectively). The proportion of patients who failed nonoperative management did not change from baseline until HD4 (23% (95% CI 19.7, 26.3) vs 33.9% (95% CI 28.3, 39.6), P-value <.001). DISCUSSION: Early mobilization of VATS before hospital day 4 increases the overall hospital cost without offering any length of stay benefit. Continuing nonoperative management longer than 4 days is associated with a high failure rate and a costlier operation.

Coagulopathy in Penetrating Ballistic Cranial Trauma: A 7-Year Experience.

BACKGROUND AND OBJECTIVES: Penetrating ballistic cranial trauma (PBCT) carries significant mortality when compared with blunt trauma. The development of coagulopathy in PBCT is a strong predictor of mortality. The goal of the study was to describe the incidence and risk factors of coagulopathy in PBCT and to report the value of tranexamic acid administration in PBCT. METHODS: We retrospectively analyzed 270 patients who presented with PBCT to a single, Level 1 trauma center between 2016 and 2023. RESULTS: A total of 47% (127/270) of patients with PBCT developed coagulopathy at presentation. Fifty-seven patients received tranexamic acid at presentation, which did not affect the development of coagulopathy. Coagulopathic patients were more likely to have more serious injury patterns (bihemispheric [adjusted odds ratio, aOR: 2.6 CI: 1.4-4.9, P = .004] or transventricular trajectories [aOR: 4.9 CI: 1.9-19.6, P = .03]). In addition, they presented with a larger base deficit (aOR: 0.9 CI: 1.002-1.2 per mEq/L, P = .006) which negatively correlated with the international normalized ratio (ρ: -0.46, P < .0001, Spearman correlation). Using thromboelastography helped to identify an additional 20% of patients who presented with normal coagulation on conventional testing. CONCLUSION: Coagulopathy is prevalent in approximately 50% of patients with PBCT and is persistent despite treatment in a substantial subset of patients. The addition of thromboelastography with its increased coagulopathy sensitivity can potentially guide treatment more efficiently than traditional coagulopathy laboratory tests and fibrinogen alone. Patients with a significant base deficit on arterial blood gas are at higher risk for coagulopathy.