ABSTRACT
BACKGROUND: The implementation of acuity circles (AC) in 2020 and the COVID-19 pandemic increased the use of local surgeons to recover livers for transplant; however, the impact on liver transplant (LT) outcomes is unknown. METHODS: Deceased donor adult LT recipients from the UNOS database were identified.⯠Recipients were grouped by donor surgeon: local versus primary recovery.⯠Patient and graft survival as well as trends in local recovery in the 2 years pre-AC and post-AC were assessed. RESULTS: The utilization of local recovery in LT increased from 22.3% to 37.9% post-AC (p < 0.01).⯠LTs with local recovery had longer cold ischemia times (6.5 h [5.4-7.8] vs. 5.3 h [4.4-6.5], p < 0.01) and traveled further (210 miles [89-373] vs. 73 miles [11-196], p < 0.01) than those using primary recovery. Multivariate analyses revealed no differences in patient or graft survival between local and primary recovery, and between OPO and local surgeon. There was no difference in survival when comparing simultaneous liver-kidney, donation after circulatory death, MELD ≥ 30, or redo-LT by recovery team.⯠Recovery and utilization rates were also noted to be higher post-AC (51.4% vs. 48.6% pre-AC, p < 0.01) as well as when OPO surgeons recovered the allografts (72.5% vs. 66.0%, p < 0.01). CONCLUSION: Nearly 40% of LTs are performed using local recovery, and utilization rates and trends continue to change with changing organ-sharing paradigms such as AC.⯠This practice appears safe with outcomes similar to recovery by the primary team in appropriately selected recipients and may lead to increased access and the ability to transplant more livers.
Subject(s)
COVID-19 , Databases, Factual , Graft Survival , Liver Transplantation , Tissue and Organ Procurement , Humans , Male , Female , Middle Aged , Tissue and Organ Procurement/statistics & numerical data , COVID-19/epidemiology , United States , Adult , Tissue Donors/supply & distribution , Tissue Donors/statistics & numerical data , SARS-CoV-2 , Aged , Survival Rate , Patient Care TeamABSTRACT
INTRODUCTION: Tranexamic acid (TXA) administered early after traumatic brain injury (TBI) can decrease morbidity and mortality. The purpose of this study is to determine if the timing of TXA administration after TBI affects postinjury inflammatory markers or phosphorylated tau (p-tau) levels within the hippocampus. METHODS: Male mice (9-11 wk) were split into six groups based on injury and timing of TXA administration (n = 5 per group): Sham, TBI-only, 100 mg/kg TXA-only, TBI + TXA 10 min, TBI + TXA 1 h, and TBI + TXA 6 h. Moderate concussive TBI was induced via weight drop. Serum and brain homogenates were collected at 6 and 24 h postinjury and analyzed for 14 inflammatory cytokines via multiplex enzyme-linked immunosorbent assay. Serum was analyzed for glial fibrillary acidic protein levels. Additional cohorts were survived to 30 d for hippocampal p-tau quantification using immunohistochemistry. RESULTS: Serum levels of interleukin (IL) 1ß (IL-1ß), IL-3, IL-12, IL-17, monocyte chemoattractant protein-1, granulocyte-macrophage colony-stimulating factor, and regulated on activation, normal T-cell expressed and secreted were elevated in TBI mice compared to sham mice at 24 h. Levels of IL-1ß and monocyte chemoattractant protein-1 were lower in 6-h TXA-treated mice than 1-h TXA-treated mice following TBI. IL-12 and macrophage inflammatory protein-1α levels were decreased in 6-h TXA-treated mice compared to 10-min TXA-treated mice. Administration of TXA at 10 min and 6 h but not 1 h postTBI reduced serum glial fibrillary acidic protein levels compared to TBI-only mice. Hippocampal p-tau accumulation was increased after TBI but not reduced by TXA administration. CONCLUSIONS: Our results demonstrate that neither early nor delayed administration of TXA conveyed significant systemic or cerebral benefit in cytokine levels following TBI. Further research should be conducted to assess blood brain barrier integrity and neurobehavioral recovery following TXA administration postTBI.
ABSTRACT
INTRODUCTION: Splenectomy (SPLN) is associated with elevated risk of venous thromboembolic (VTE) disease. Enoxaparin (ENX) is a low-molecular-weight heparin agent used in VTE chemoprophylaxis. Early aspirin administration ameliorates postSPLN platelet hyperaggregability in male mice. Previous literature has excluded female mice, citing potential effects of estrogen on platelet count and activation as a reason. We hypothesized that multimodal therapy using aspirin and ENX would mitigate postoperative platelet aggregability in mice across sexes. METHODS: Murine models of SPLN included both male and female mice. Treatment groups included placebo gavage, sham laparotomy, SPLN alone, SPLN and aspirin, SPLN and ENX, and SPLN with aspirin and ENX (n = 5 per group). Chemoprophylaxis dosing was initiated before SPLN. Mice were euthanized on post-operative day (POD) 1 or 3; platelet counts were obtained and blood samples were analyzed via electrical impedance aggregometry. RESULTS: Females on POD 3 following SPLN demonstrated increased platelet count compared to female mice with no treatment intervention. Male and female mice demonstrated increased adenosine diphosphate (ADP)-induced platelet aggregability on POD 3 following SPLN compared to the placebo group. Treatment with aspirin and ENX decreased this post-SPLN platelet hyperaggregability in both sexes. Females demonstrated significantly higher ADP-mediated platelet aggregability in placebo, SPLN, and SPLN with aspirin and ENX when compared to males of identical treatment groups on POD 3. CONCLUSIONS: Platelet hyperaggregability following SPLN is mediated primarily by ADP in both males and females, but higher relative aggregability is demonstrated in females. Early administration of dual-agent VTE chemoprophylaxis utilizing aspirin and ENX mitigates this hyperaggregability and may aid in VTE risk reduction across sexes.
ABSTRACT
INTRODUCTION: The Parkland Trauma Index of Mortality (PTIM) is an integrated, machine learning 72-h mortality prediction model that automatically extracts and analyzes demographic, laboratory, and physiological data in polytrauma patients. We hypothesized that this validated model would perform equally as well at another level 1 trauma center. METHODS: A retrospective cohort study was performed including â¼5000 adult level 1 trauma activation patients from January 2022 to September 2023. Demographics, physiologic and laboratory values were collected. First, a test set of models using PTIM clinical variables (CVs) was used as external validation, named PTIM+. Then, multiple novel mortality prediction models were developed considering all CVs designated as the Cincinnati Trauma Index of Mortality (CTIM). The statistical performance of the models was then compared. RESULTS: PTIM CVs were found to have similar predictive performance within the PTIM + external validation model. The highest correlating CVs used in CTIM overlapped considerably with those of the PTIM, and performance was comparable between models. Specifically, for prediction of mortality within 48 h (CTIM versus PTIM): positive prediction value was 35.6% versus 32.5%, negative prediction value was 99.6% versus 99.3%, sensitivity was 81.0% versus 82.5%, specificity was 97.3% versus 93.6%, and area under the curve was 0.98 versus 0.94. CONCLUSIONS: This external cohort study suggests that the variables initially identified via PTIM retain their predictive ability and are accessible in a different level 1 trauma center. This work shows that a trauma center may be able to operationalize an effective predictive model without undertaking a repeated time and resource intensive process of full variable selection.
ABSTRACT
BACKGROUND: The demand for liver transplants (LT) in the United States far surpasses the availability of allografts. New allocation schemes have resulted in occasional difficulties with allograft placement and increased intraoperative turndowns. We aimed to evaluate the outcomes related to use of late-turndown liver allografts. METHODS: A review of prospectively collected data of LTs at a single center from July 2019 to July 2023 was performed. Late-turndown placement was defined as an open offer 6 h prior to donation, intraoperative turndown by primary center, or post-cross-clamp turndown. RESULTS: Of 565 LTs, 25.1% (n = 142) received a late-turndown liver allograft. There were no significant differences in recipient age, gender, BMI, or race (all p > 0.05), but MELD was lower for the late-turndown LT recipient group (median 15 vs 21, p < 0.001). No difference in 30-day, 6-month, or 1-year survival was noted on logistic regression, and no difference in patient or graft survival was noted on Cox proportional hazard regression. Late-turndown utilization increased during the study from 17.2% to 25.8%, and median waitlist time decreased from 77 days in 2019 to 18 days in 2023 (p < 0.001). CONCLUSION: Use of late-turndown livers has increased and can increase transplant rates without compromising post-transplant outcomes with appropriate selection.
ABSTRACT
INTRODUCTION: Hypoxia is a significant cause of secondary insult in the critically ill trauma or surgical patient. The cause of increased mortality following a brief period of hypoxia is not well understood. The aim of this study is to determine the effect of acute, isolated deviations in oxygen concentration on proinflammatory cytokine release and markers of endothelial stress in a murine model. METHODS: Mice were randomized to either control, hypoxia, or hyperoxia group. The control group was exposed to room air for 60 min, the hyperoxia group was exposed to 70% fraction of inspired oxygen, and the hypoxia group was exposed to 10% fraction of inspired oxygen for 60 min. Whole blood collection was completed via cardiac puncture. Serum concentrations of proinflammatory cytokines and endothelial stress markers were analyzed via enzyme-linked immunosorbent assay. RESULTS: Following exposure to hypoxic conditions, there was a significant increase in interleukin (IL)-1α (IL-1 α), IL-1 ß, IL-3, IL-4, IL-6, IL-10, tumor necrosis factor α . Following exposure to hyperoxic conditions, there was a significant increase in monocyte chemoattractant protein-1 and regulated upon activation normal T cell expressed and presumably secreted, as well as a significant decrease in IL-12, and IL-17. No clinically significant difference was noted in serum concentration of endothelial stress markers between the treatment groups. DISCUSSION: Exposure to oxygen extremes induces systemic inflammation as measured by proinflammatory cytokines in a murine model. Hyperoxia also demonstrates the ability to downregulate certain inflammatory pathways while inducing others. No effect on serum concentration of endothelial stress markers is observed following acute, isolated hypoxic or hyperoxic conditions.
ABSTRACT
INTRODUCTION: Many patients suffering from isolated severe traumatic brain injury (sTBI) receive blood transfusion on hospital arrival due to hypotension. We hypothesized that increasing blood transfusions in isolated sTBI patients would be associated with an increase in mortality. METHODS: We performed a trauma quality improvement program (TQIP) (2017-2019) and single-center (2013-2021) database review filtering for patients with isolated sTBI (Abbreviated Injury Scale head ≥3 and all other areas ≤2). Age, initial Glasgow Coma Score (GCS), Injury Severity Score (ISS), initial systolic blood pressure (SBP), mechanism (blunt/penetrating), packed red blood cells (pRBCs) and fresh frozen plasma (FFP) transfusion volume (units) within the first 4 h, FFP/pRBC ratio (4h), and in-hospital mortality were obtained from the TQIP Public User Files. RESULTS: In the TQIP database, 9257 patients had isolated sTBI and received pRBC transfusion within the first 4 h. The mortality rate within this group was 47.3%. The increase in mortality associated with the first unit of pRBCs was 20%, then increasing approximately 4% per unit transfused to a maximum mortality of 74% for 11 or more units. When adjusted for age, initial GCS, ISS, initial SBP, and mechanism, pRBC volume (1.09 [1.08-1.10], FFP volume (1.08 [1.07-1.09]), and FFP/pRBC ratio (1.18 [1.08-1.28]) were associated with in-hospital mortality. Our single-center study yielded 138 patients with isolated sTBI who received pRBC transfusion. These patients experienced a 60.1% in-hospital mortality rate. Logistic regression corrected for age, initial GCS, ISS, initial SBP, and mechanism demonstrated no significant association between pRBC transfusion volume (1.14 [0.81-1.61]), FFP transfusion volume (1.29 [0.91-1.82]), or FFP/pRBC ratio (6.42 [0.25-164.89]) and in-hospital mortality. CONCLUSIONS: Patients suffering from isolated sTBI have a higher rate of mortality with increasing amount of pRBC or FFP transfusion within the first 4 h of arrival.
ABSTRACT
BACKGROUND: Traumatic brain injury (TBI)-related morbidity is caused largely by secondary injury resulting from hypoxia, excessive sympathetic drive, and uncontrolled inflammation. Aeromedical evacuation (AE) is utilized by the military for transport of wounded soldiers to higher levels of care. We hypothesized that the hypobaric, hypoxic conditions of AE may exacerbate uncontrolled inflammation following TBI that could contribute to more severe TBI-related secondary injury. STUDY DESIGN: Thirty-six female pigs were used to test TBI vs. TBI sham, hypoxia vs. normoxia, and hypobaria vs. ground conditions. TBI was induced by controlled cortical injury, hypobaric conditions of 12,000 feet were established in an altitude chamber, and hypoxic exposure was titrated to 85% SpO2 while at altitude. Serum cytokines, UCH-L1 and TBI biomarkers were analyzed via ELISA. Gross analysis and staining of cortex and hippocampus tissue was completed for glial fibrillary acidic protein (GFAP) and phosphorylated tau (p-tau). RESULTS: Serum IL-1b, IL-6, and TNFα were significantly elevated following TBI in pigs exposed to altitude-induced hypobaria/hypoxia, as well as hypobaria alone, compared to ground level/normoxia. No difference in TBI biomarkers following TBI or hypobaric, hypoxic exposure was noted. No difference in brain tissue GFAP or p-tau when comparing the most different conditions of sham TBI+ground/normoxia to the TBI+hypobaria/hypoxia group was noted. CONCLUSION: The hypobaric environment of AE induces systemic inflammation following TBI. Severe inflammation may play a role in exacerbating secondary injury associated with TBI and contribute to worse neurocognitive outcomes. Measures should be taken to minimize barometric and oxygenation changes during AE following TBI.
ABSTRACT
INTRODUCTION: Blunt cardiac injury (BCI) can be challenging diagnostically, and if misdiagnosed, can lead to life-threatening complications. Our institution previously evaluated BCI screening with troponin and electrocardiogram (EKG) during a transition from troponin I to high sensitivity troponin (hsTnI), a more sensitive troponin I assay. The previous study found an hsTnI of 76 ng/L had the highest capability of accurately diagnosing a clinically significant BCI. The aim of this study was to determine the efficacy of the newly implemented protocol. METHODS: Patients diagnosed with a sternal fracture from March 2022 to April 2023 at our urban level-1 trauma center were retrospectively reviewed for EKG findings, hsTnI trend, echocardiogram changes, and clinical outcomes. The BCI cohort and non-BCI cohort ordinal measures were compared using Wilcoxon's two-tailed rank sum test and categorical measures were compared with Fisher's exact test. Youden indices were used to evaluate hsTnI sensitivity and specificity. RESULTS: Sternal fractures were identified in 206 patients, of which 183 underwent BCI screening. Of those screened, 103 underwent echocardiogram, 28 were diagnosed with clinically significant BCIs, and 15 received intervention. The peak hsTnI threshold of 76 ng/L was found to have a Youden index of 0.31. Rather, the Youden index was highest at 0.50 at 40 ng/L (sensitivity 0.79 and specificity 0.71) for clinically significant BCI. CONCLUSIONS: Screening patients with sternal fractures for BCI using hsTnI and EKG remains effective. To optimize the hsTnI threshold, this study determined the hsTnI threshold should be lowered to 40 ng/L. Further improvements to the institutional protocol may be derived from multicenter analysis.
Subject(s)
Electrocardiography , Wounds, Nonpenetrating , Humans , Female , Retrospective Studies , Male , Middle Aged , Adult , Wounds, Nonpenetrating/diagnosis , Wounds, Nonpenetrating/blood , Aged , Heart Injuries/diagnosis , Heart Injuries/blood , Troponin I/blood , Sternum/injuries , Sensitivity and Specificity , Biomarkers/blood , Fractures, Bone/blood , Fractures, Bone/diagnosis , EchocardiographyABSTRACT
BACKGROUND: Prior literature has implicated red blood cells (RBCs) in the initiation of thrombosis and suggests that posttransfusion hypercoagulability may occur secondary to the effects of RBCs. Elevated serum tissue factor is a known sequelae of acute trauma. Phosphatidylserine (PS) is a prothrombotic phospholipid present within the RBC cell membrane. We hypothesized that RBC aggregation is dependent on the interaction between RBC membrane bound (exposed) PS, extracellular calcium, and tissue factor. METHODS: Human whole blood (WB) was separated into components, including RBCs and platelet-rich plasma (PRP). Whole blood, PRP, and RBCs underwent impedance aggregometry utilizing arachidonic acid (AA), ADP, collagen, calcium, and tissue factor (TF)-based agonists. Red blood cells then underwent impedance aggregometry utilizing combined calcium and TF agonists. Red blood cells were pretreated with Annexin V, a known PS blocking agent, and underwent impedance aggregometry with combined calcium and TF agonists to determine if the mechanism of calcium/TF-induced RBC aggregability is dependent on PS. Red blood cells treated with calcium, TF, calcium+TF, and pre-treated with Annexin V followed by calcium+TF were perfused through an in vitro model of pulmonary microcirculatory flow. RESULTS: Red blood cell aggregation was significantly higher than that of WB and PRP when utilizing a TF agonist, an effect unique to TF. The combination of calcium and TF demonstrated significantly higher RBC aggregation than either agonist alone. Pretreatment with Annexin V resulted in a significantly reduced aggregability of RBC following treatment with TF + calcium. Red blood cells aged to 42 days did not exhibit significant change in aggregation. Exposure to calcium and TF significantly reduced time to thrombosis of RBCs perfused through a pulmonary microcirculatory model. CONCLUSION: Treatment with both TF and calcium synergistically induces RBC aggregation. Phosphatidylserine appears to play an integral role in the TF/calcium-based, age-independent RBC aggregation response. Red blood cells treated with TF + calcium exhibit more rapid thrombus formation in an in vitro model of pulmonary microcirculatory perfusion.
Subject(s)
Calcium , Erythrocytes , Phosphatidylserines , Thromboplastin , Thrombosis , Humans , Phosphatidylserines/metabolism , Thromboplastin/metabolism , Calcium/metabolism , Thrombosis/metabolism , Thrombosis/etiology , Erythrocytes/metabolism , Erythrocyte Aggregation/drug effects , Erythrocyte Membrane/metabolism , Platelet-Rich Plasma/metabolismABSTRACT
INTRODUCTION: The mechanism of post-traumatic brain injury (TBI) hypoxemia involves ventilation/perfusion mismatch and loss of pulmonary hypoxic vasoconstriction. Inhaled nitric oxide (iNO) has been studied as an adjunct treatment to avoid the use of high positive end-expiratory pressure and inspired oxygen in treatment-refractory hypoxia. We hypothesized that iNO treatment following TBI would improve systemic and cerebral oxygenation via improved matching of pulmonary perfusion and ventilation. METHODS: Thirteen human patients with isolated TBI were enrolled and randomized to receive either placebo or iNO with measured outcomes including pulmonary parameters, blood gas data, and intracranial pressure (ICP) /perfusion. To complement this study, a porcine model of TBI (including 10 swine) was utilized with measured outcomes of brain tissue blood flow and oxygenation, ventilator parameters, and blood gas data both after administration and following drug removal and clearance. RESULTS: There were no clinically significant changes in pulmonary parameters in either the human or porcine arm following administration of iNO when compared to either the placebo group (human arm) or the internal control (porcine arm). Analysis of pooled human data demonstrated the preservation of alveolar recruitment in TBI patients. There were no clinically significant changes in human ICP or cerebral perfusion pressure following iNO administration compared to controls. CONCLUSIONS: iNO had no significant effect on clinically relevant pulmonary parameters or ICPs following TBI in both human patients and a porcine model. The pressure-based recruitment of the human lungs following TBI was preserved. Further investigation will be needed to determine the degree of utility of iNO in the setting of hypoxia after polytrauma.
Subject(s)
Brain Injuries, Traumatic , Nitric Oxide , Humans , Animals , Swine , Lung , Hypoxia , Brain Injuries, Traumatic/complications , Brain Injuries, Traumatic/drug therapy , Vasoconstriction , Administration, InhalationABSTRACT
INTRODUCTION: Desmopressin (DDAVP) has been utilized clinically in patients taking aspirin (ASA) to improve drug-induced platelet dysfunction. Misoprostol and carboprost, prostaglandin analogs commonly used for postpartum hemorrhage, may also induce platelet aggregation. The aim of this study was to determine the effects of DDAVP, misoprostol, and carboprost administration on platelet aggregability following traumatic brain injury (TBI) in mice treated with ASA. METHODS: Male C57BL/6 mice were randomized into seven groups (n = 5 each): untouched, ASA only, Saline/TBI, ASA/TBI, ASA/TBI/DDAVP 0.4 µg/kg, ASA/TBI/misoprostol 1 mg/kg, and ASA/TBI/carboprost 100 µg/kg. TBI was induced via a weight drop model 4-h after ASA (50 mg/kg) gavage. Mice were given an intraperitoneal injection of DDAVP, misoprostol, or carboprost 10 minutes after TBI. In vivo testing was completed utilizing tail vein bleed. Mice were sacrificed 30-min posttreatment and blood was collected via cardiac puncture. Whole blood was analyzed via Multiplate impedance aggregometry, rotational thromboelastometry, and TEG6s. RESULTS: Mice receiving misoprostol after ASA/TBI demonstrated decreased tail vein bleeding times compared to ASA only treated mice. However, mice treated with misoprostol following ASA and TBI demonstrated decreased platelet aggregability compared to untouched mice and TBI only mice within the arachidonic acid agonist pathway. By contrast, DDAVP and carboprost did not significantly change platelet aggregability via adenosine diphosphate or arachidonic acid following ASA and TBI. However, DDAVP did decrease the platelet contribution to clot via rotational thromboelastometry. CONCLUSIONS: Reversal of medication-induced platelet inhibition has become increasingly controversial after TBI. Based on these results, DDAVP, misoprostol, nor carboprost consistently improve platelet aggregability following TBI in those also treated with ASA.
Subject(s)
Brain Injuries, Traumatic , Carboprost , Misoprostol , Humans , Female , Male , Mice , Animals , Aspirin/pharmacology , Aspirin/therapeutic use , Deamino Arginine Vasopressin/pharmacology , Deamino Arginine Vasopressin/therapeutic use , Carboprost/pharmacology , Misoprostol/pharmacology , Misoprostol/therapeutic use , Arachidonic Acid/pharmacology , Mice, Inbred C57BL , Platelet Aggregation/physiology , Platelet Aggregation Inhibitors/pharmacology , Platelet Aggregation Inhibitors/therapeutic use , Brain Injuries, Traumatic/complications , Brain Injuries, Traumatic/drug therapyABSTRACT
INTRODUCTION: Various murine models have been utilized to study TBI, including closed head injury (CHI) and controlled cortical impact (CCI), without direct comparison. The aim of our study was to evaluate these models to determine differences in neurological and behavioral outcomes postinjury. METHODS: Male C57B/6 mice (9-10 wk) were separated into six groups including: untouched, sham craniotomy (4 mm), CCI 0.9 mm depth of impact, CCI 1.6 mm, CCI 2.2 mm, and CHI. CCI was performed using a 3 mm impact tip at a velocity of 5 m/s, dwell time of 250 ms, and depth as noted above. CHI was completed with a centered 400 g weight drop from 1 cm height. Mice were survived to 14-d (n = 5 per group) and 30-d (n = 5 per group) respectively for histological analysis of p-tau within the hippocampus. These mice underwent Morris Water Maze memory testing and Rotarod motor testing. Serum was collected from a separate cohort of mice (n = 5 per group) including untouched, isoflurane only, CCI 1.6 mm, CHI at 1, 4, 6, and 24 h for analysis of neuron specific enolase and glial fibrillary acidic protein (GFAP) via ELISA. Laser speckle contrast imaging was analyzed prior to and after impact in the CHI and CCI 1.6 mm groups. RESULTS: There were no significant differences in Morris Water Maze or Rotarod testing times between groups at 14- or 30-d. P-tau was significantly elevated in all groups except CCI 1.6 mm contralateral and CCI 2.2 mm ipsilateral compared to untouched mice at 30-d. P-tau was also significantly elevated in the CHI group at 30 d compared to CCI 1.6 mm contralateral and CCI 2.2 mm on both sides. GFAP was significantly increased in mice undergoing CHI (9959 ± 91 pg/mL) compared to CCI (2299 ± 1288 pg/mL), isoflurane only (133 ± 75 pg/mL), and sham (86 ± 58 pg/mL) at 1-h post TBI (P < 0.0001). There were no differences in serum neuron specific enolase levels between groups. Laser doppler imaging demonstrated similar decreases in cerebral blood flow between CHI and CCI; however, CCI mice had a reduction in blood flow with craniotomy only that did not significantly decrease further with impact. CONCLUSIONS: Based on our findings, CHI leads to increased serum GFAP levels and increased p-tau within the hippocampus at 30-d postinjury. While CCI allows the comparison of one cerebral hemisphere to the other, CHI may be a better model of TBI as it requires less technical expertise and has similar neurological outcomes in these murine models.
Subject(s)
Brain Injuries, Traumatic , Head Injuries, Closed , Isoflurane , Humans , Mice , Animals , Male , Hippocampus/pathology , Phosphopyruvate Hydratase , Disease Models, AnimalABSTRACT
BACKGROUND: Prior analyses of general surgery resident case logs have indicated a decline in the number of endocrine procedures performed during residency. This study aimed to identify factors contributing to the endocrine operative experience of general surgery residents and compare those who matched in endocrine surgery fellowship with those who did not. METHODS: We analyzed the case log data of graduates from 18 general surgery residency programs in the US Resident Operative Experience Consortium over an 11-year period. RESULTS: Of the 1,240 residents we included, 17 (1%) matched into endocrine surgery fellowships. Those who matched treated more total endocrine cases, including more thyroid, parathyroid, and adrenal cases, than those who did not (81 vs 37, respectively, P < .01). Program-level factors associated with increased endocrine volume included endocrine-specific rotations (+10, confidence interval 8-12, P < .01), endocrine-trained faculty (+8, confidence interval 7-10, P < .01), and program co-location with otolaryngology residency (+5, confidence interval 2 -8, P < .01) or endocrine surgery fellowship (+4, confidence interval 2-6, P < .01). Factors associated with decreased endocrine volume included bottom 50th percentile in National Institute of Health funding (-10, confidence interval -12 to -8, P < .01) and endocrine-focused otolaryngologists (-3, confidence interval -4 to -1, P < .01). CONCLUSION: Several characteristics are associated with a robust endocrine experience and pursuit of an endocrine surgery fellowship. Modifiable factors include optimizing the recruitment of dedicated endocrine surgeons and the inclusion of endocrine surgery rotations in general surgery residency.
Subject(s)
Endocrine Surgical Procedures , General Surgery , Internship and Residency , Surgeons , Humans , Fellowships and Scholarships , General Surgery/education , Education, Medical, Graduate/methods , Clinical CompetenceABSTRACT
INTRODUCTION: Syndecan-1 is a heparan sulfate proteoglycan found in the glycocalyx of vascular endothelial cells. Serum levels of syndecan-1 have repeatedly been demonstrated to increase following traumatic injury and shock, but it is unclear whether syndecan-1 plays an active role in the inflammatory response or is simply a biomarker of a state of hypoperfusion. The aim of this study was to identify the role of syndecan-1 role in the inflammatory process in the absence of trauma. METHODS: Male mice were randomized into five groups (n = 3). Four groups received increasing concentrations of syndecan-1 (1, 10, 100, and 1000pg/mL per blood volume) and a fifth group was given normal saline as a control via intravenous injection. These concentrations were selected based on previous syndecan-1 enzyme-linked immunosorbent assay data acquired following induced hemorrhagic shock in mice resulting in serum levels of 10-6000 pg/mL. Mice from each group were sacrificed at 1-, 4-, and 24-h time points for serum biomarker evaluation. A multiplex enzyme-linked immunosorbent assay was performed to analyze proinflammatory cytokines and chemokines including interleukin (IL)-1a, IL-1b, IL-2, IL-3, IL-4, IL-6, IL-10, IL-12, IL-17, monocyte chemoattractant protein-1, TNF-α, macrophage inflammatory protein-1α, granulocyte-macrophage colony-stimulating factor, and normal T cell expressed and presumably secreted levels. Whole blood was analyzed via rotational thromboelastometry in a separate group of mice dosed with syndecan-1 at 1000 pg/mL and compared to sham mice at 1 h. RESULTS: Tumor necrosis factor-α was significantly elevated in the 1000 pg/mL group compared to sham animals. There were no significant changes in IL-1a, IL-1b, IL-2, IL-3, IL-4, IL-6, IL-10, IL-12, monocyte chemoattractant protein--1, macrophage inflammatory protein-1α, granulocyte-macrophage colony-stimulating factor, or normal T cell expressed and presumably secretedat 1, 4, and 24 h for any group when compared to mice receiving saline alone. No significant differences were noted in coagulability between the 1000 pg/mL syndecan-1 group and shams at 1 h CONCLUSIONS: Inflammatory cytokine concentrations did not change with increasing dosage of syndecan-1 within mice at any timepoint, except for an acute change in tumor necrosis factor-α which was transient. Based on our results, syndecan-1 appears to be a biomarker for inflammation rather than an active participant in eliciting an inflammatory response. Further research will focus on the role of syndecan-1 following hemorrhagic shock.
Subject(s)
Granulocyte-Macrophage Colony-Stimulating Factor , Shock, Hemorrhagic , Humans , Male , Mice , Animals , Interleukin-10 , Interleukin-6 , Endothelial Cells , Tumor Necrosis Factor-alpha , Shock, Hemorrhagic/complications , Syndecan-1 , Interleukin-2 , Interleukin-3 , Interleukin-4 , Cytokines , Interleukin-12 , Biomarkers , Macrophage Inflammatory ProteinsABSTRACT
INTRODUCTION: Dynamic preload assessment measures including pulse pressure variation (PPV), stroke volume variation (SVV), pleth variability index (PVI), and hypotension prediction index (HPI) have been utilized clinically to guide fluid management decisions in critically ill patients. These values aid in the balance of correcting hypotension while avoiding over-resuscitation leading to respiratory failure and increased mortality. However, these measures have not been previously validated at altitude or in those with temporary abdominal closure (TAC). METHODS: Forty-eight female swine (39 ± 2 kg) were separated into eight groups (n = 6) including all combinations of flight versus ground, hemorrhage versus no hemorrhage, and TAC versus no TAC. Flight animals underwent simulated aeromedical evacuation via an altitude chamber at 8000 ft. Hemorrhagic shock was induced via stepwise hemorrhage removing 10% blood volume in 15-min increments to a total blood loss of 40% or a mean arterial pressure of 35 mmHg. Animals were then stepwise transfused with citrated shed blood with 10% volume every 15 min back to full blood volume. PPV, SVV, PVI, and HPI were monitored every 15 min throughout the simulated aeromedical evacuation or ground control. Blood samples were collected and analyzed for serum levels of serum IL-1ß, IL-6, IL-8, and TNF-α. RESULTS: Hemorrhage groups demonstrated significant increases in PPV, SVV, PVI, and HPI at each step compared to nonhemorrhage groups. Flight increased PPV (P = 0.004) and SVV (P = 0.003) in hemorrhaged animals. TAC at ground level increased PPV (P < 0.0001), SVV (P = 0.0003), and PVI (P < 0.0001). When TAC was present during flight, PPV (P = 0.004), SVV (P = 0.003), and PVI (P < 0.0001) values were decreased suggesting a dependent effect between altitude and TAC. There were no significant differences in serum IL-1ß, IL-6, IL-8, or TNF-α concentration between injury groups. CONCLUSIONS: Based on our study, PPV and SVV are increased during flight and in the presence of TAC. Pleth variability index is slightly increased with TAC at ground level. Hypotension prediction index demonstrated no significant changes regardless of altitude or TAC status, however this measure was less reliable once the resuscitation phase was initiated. Pleth variability index may be the most useful predictor of preload during aeromedical evacuation as it is a noninvasive modality.
Subject(s)
Hemodynamics , Hypotension , Humans , Female , Animals , Swine , Stroke Volume , Altitude , Tumor Necrosis Factor-alpha , Interleukin-6 , Interleukin-8 , Blood Pressure , Hemorrhage/diagnosis , Hemorrhage/etiology , Hemorrhage/therapy , Fluid TherapyABSTRACT
INTRODUCTION: Technical learning in surgical training is multifaceted and existing literature suggests a positive relationship between case volume and proficiency. Little is known about factors associated with a decreased volume of operative experience. This study aimed to identify resident and program factors associated with general surgery residents (GSR) in the bottom quartile of logged case volume upon program completion. METHODS: A post hoc analysis of a multicenter study was used to examine case logs for categorical GSR. Participants included graduates between 2010 and 2020 from 20 programs. Residents below and above the 25th percentile for total operative volume were compared. RESULTS: The present study includes 1343 GSR who graduated over the 11-y period. In total, 336 residents were below the 25th percentile and 1007 residents were above the 25th percentile. Those below the 25th percentile were more likely to be female (41% versus 34%, P = 0.02), identify as underrepresented in medicine (22% versus 14%, P < 0.01), and pursue fellowship (86% versus 80%, P = 0.01) compared to those above the 25th percentile. Residents below the 25th percentile were more likely to have graduated from a low volume program (55% versus 25%, P < 0.01) and from top National Institutes of Health funded institutions (57% versus 52%, P = 0.01). CONCLUSIONS: This study identified individual and program characteristics associated with lower operative volume of GSR. Understanding such characteristics will aid surgical educators to achieve better equity in training.
Subject(s)
General Surgery , Internship and Residency , Medicine , Humans , Female , Male , Clinical Competence , Education, Medical, Graduate , Fellowships and Scholarships , General Surgery/educationABSTRACT
BACKGROUND: Temporary abdominal closure is commonly employed in liver transplantation when patient factors make primary fascial closure challenging. However, there is minimal data evaluating long-term survival and patient outcomes after temporary abdominal closure. METHODS: A single-center, retrospective review of patients undergoing liver transplantation from January 2013 through December 2017 was performed with a 5-year follow-up. Patients were characterized as either requiring temporary abdominal closure or immediate primary fascial closure at the time of liver transplantation. RESULTS: Of 422 patients who underwent 436 liver transplantations, 17.2% (n = 75) required temporary abdominal closure, whereas 82.8% (n = 361) underwent primary fascial closure. Patients requiring temporary abdominal closure had higher Model for End-Stage Liver Disease scores preoperatively (27 [22-36] vs 23 [20-28], P = .0002), had higher rates of dialysis preoperatively (28.0% vs 12.5%, P = .0007), and were more likely to be hospitalized within 90 days of liver transplantation (64.0% vs 47.5%, P = .0093). On univariable analysis, survival at 1 year was different between the groups (90.9% surviving at 1 year for primary fascial closure versus 82.7% for temporary abdominal closure, P = .0356); however, there was no significant difference in survival at 5 years (83.7% vs 76.0%, P = .11). On multivariable analysis, there was no difference in survival after adjusting for multiple factors. Patients requiring temporary abdominal closure were more likely to have longer hospital stays (median 16 days [9.75-29.5] vs 8 days [6-14], P < .0001), more likely to be readmitted within 30 days (45.3% vs 32.2%, P = .03), and less likely to be discharged home (36.5% vs 74.2%, P < .0001). CONCLUSIONS: Temporary abdominal closure after liver transplantation appears safe and has similar outcomes to primary fascial closure, though it is used more commonly in complex patients.
Subject(s)
Abdominal Injuries , Abdominal Wound Closure Techniques , End Stage Liver Disease , Liver Transplantation , Humans , Liver Transplantation/adverse effects , Follow-Up Studies , End Stage Liver Disease/surgery , Severity of Illness Index , Abdomen/surgery , Laparotomy , Retrospective Studies , Abdominal Injuries/surgeryABSTRACT
INTRODUCTION: Seven key inflammatory biomarkers were recently found to be associated with the risk of mortality in a multicenter study of massively transfused patients. The aim of this prospective single-center study was to determine which of these early inflammatory markers could predict 30-d mortality among all critically injured trauma patients. METHODS: Serum samples were collected at 6, 24, and 72 h from 238 consecutive patients admitted to the intensive care unit following traumatic injury. Inflammatory markers syndecan-1, eotaxin, IL-1ra, IL-6, IL-8, IL-10, IP-10, and MCP-1 were analyzed via multiplex enzyme-linked immunosorbent assay. Subgroup analysis was performed for patients undergoing massive transfusion (≥5 red blood cells), submassive transfusion (1-4 red blood cells), or no transfusion during the first 4 h postinjury. The primary outcome of 30-d survival was modeled as a function of each biomarker and confounders using repeat measures logistic regression. RESULTS: Patients had a median age of 51.3 y [33.7, 70.2], 70.6% were male, 17.4% experienced penetrating trauma, and had a median injury severity score of 22 [14, 33]. IL-1ra, IL-8, IL-10, and MCP-1 were significantly increased during the first 72 h in nonsurvivors (n = 31). Elevated IL-1ra, IL-8, IL-10, and MCP-1 at 6 h postinjury were associated with 30-d mortality. By contrast, serum syndecan-1 and eotaxin levels were not associated with mortality at any time point. IL-8 and lactate were increased at 6 h in 30-d nonsurvivors for patients receiving submassive transfusion (n = 78). CONCLUSIONS: Early evaluations of IL-1ra, IL-8, IL-10, and IP-10 within 6 h of injury are useful predictors of 30-d mortality. Subgroup analysis suggests that transfusion status does not significantly affect early inflammatory markers. LEVEL OF EVIDENCE: Level III, prognostic/epidemiological.