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1.
J Surg Res ; 300: 150-156, 2024 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-38815513

RESUMO

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.

2.
J Surg Res ; 300: 25-32, 2024 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-38795670

RESUMO

INTRODUCTION: Previous literature suggests that sphingolipids may impact systemic coagulation and platelet aggregation, thus modulating the risks of thrombotic events. The goal of this investigation was to evaluate the role of serum sphingolipids on intrinsic platelet function to assess whether pharmacologic manipulation of sphingolipid metabolites would impact platelet aggregability. METHODS: C57BL/6J mice were injected with either normal saline, 1 mg/kg FTY720 (synthetic sphingosine-1-phosphate [S1P] receptor analog), or 5 mg/kg SLM6031434 (sphingosine kinase two inhibitor). Mice were sacrificed at 6 h and whole blood (WB) was collected for impedance aggregometry assessing platelet responsiveness to arachidonic acid or adenosine diphosphate. Ex vivo studies utilized WB or platelet-rich plasma that was pretreated with S1P, FTY720, amitriptyline, or d-sphingosine then analyzed by aggregability and flow cytometry for platelet and platelet-derived microvesicle characteristics. RESULTS: FTY720 and SLM6031434 pretreated induced similar arachidonic acid and adenosine diphosphate-mediated platelet aggregation as controls. Ex vivo WB and platelet-rich plasma treatment with S1P, FTY720, amitriptyline and d-sphingosine did not impact platelet aggregation. The percentages of CD41+, CD62P+ and CD41+/ceramide+, CD62P+/ceramide + platelets, and platelet-derived microvesicle were not significantly different between amitriptyline-treated and normal saline-treated cohorts. CONCLUSIONS: Sphingolipid modulating agents, such as FTY720, SLM6031434, S1P, amitriptyline, ceramide, and d-sphingosine do not appear to independently impact platelet aggregation in murine models.

3.
J Pharm Pract ; 36(4): 1002-1007, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35227117

RESUMO

Background: Andexanet alfa (andexanet) is the only FDA-approved medication for reversal of apixaban and rivaroxaban anticoagulation for life-threatening or uncontrolled bleeding. Infusion modifications may be required in surgical patients undergoing prolonged operative intervention but have not previously been described. Case Report: A 78-year-old woman on rivaroxaban for atrial fibrillation was admitted to the trauma service for a mechanical fall, sustaining a T4 burst fracture with severe canal stenosis and spinal cord edema resulting in loss of strength and sensation in her legs. Clinically relevant rivaroxaban activity was verified with an elevated low molecular weight heparin anti-factor Xa assay, and laboratory confirmed coagulopathy was demonstrated by a prolonged prothrombin time, thromboelastography (TEG) R-time, and activated clotting time (ACT). The patient required urgent surgical intervention for spinal fixation. Given the expected prolonged duration of the procedure, standard dose andexanet was initiated with a prolonged infusion at half the standard rate during the operation. The procedure was successful and intraoperative TEGs demonstrated normalization of R-time and ACT throughout the procedure. The patient did not experience any complications postoperatively and successfully discharged to inpatient rehabilitation. Conclusion: Modifications to the andexanet infusion may be required in surgical patients requiring rivaroxaban reversal for a prolonged procedure. Further data are needed to determine the optimal approach to infusion modification.


Assuntos
Inibidores do Fator Xa , Rivaroxabana , Humanos , Feminino , Idoso , Hemorragia/tratamento farmacológico , Fator Xa/uso terapêutico , Proteínas Recombinantes/uso terapêutico , Anticoagulantes/uso terapêutico
4.
J Surg Res ; 281: 104-111, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36152398

RESUMO

INTRODUCTION: Screening for blunt cardiac injury (BCI) includes obtaining a serum troponin level and an electrocardiogram for patients diagnosed with a sternal fracture. Our institution has transitioned to the use of a high sensitivity troponin I (hsTnI). The aim of this study was to determine whether hsTnI is comparable to troponin I (TnI) in identifying clinically significant BCI. MATERIALS AND METHODS: Trauma patients presenting to a level I trauma center over a 24-mo period with the diagnosis of sternal fracture were screened for BCI. Any initial TnI more than 0.04 ng/mL or hsTnI more than 18 ng/L was considered positive for potential BCI. Clinically significant BCI was defined as a new-bundle branch block, ST wave change, echocardiogram change, or need for cardiac catheterization. RESULTS: Two hundred sixty five patients with a sternal fracture were identified, 161 underwent screening with TnI and 104 with hsTnI. For TnI, the sensitivity and specificity for detection of clinically significant BCI was 0.80 and 0.79, respectively. For hsTnI, the sensitivity and specificity for detection of clinically significant BCI was 0.71 and 0.69, respectively. A multivariate analysis demonstrated the odds ratio for significant BCI with a positive TnI was 14.4 (95% confidence interval, 3.9-55.8, P < 0.0001) versus an odds ratio of 5.48 (95% confidence interval 1.9-15.7, P = 0.002) in the hsTnI group. CONCLUSIONS: The sensitivity of hsTnI is comparable to TnI for detection of significant BCI. Additional investigation is needed to determine the necessity and interval for repeat testing and the need for additional diagnostic testing.


Assuntos
Contusões Miocárdicas , Traumatismos Torácicos , Humanos , Troponina I , Sensibilidade e Especificidade , Eletrocardiografia , Biomarcadores
5.
J Surg Res ; 283: 33-41, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36368273

RESUMO

INTRODUCTION: The COVID-19 pandemic forced a sudden change from in-person to virtual interviews for the general surgery residency match. General surgery programs and applicants adopted multiple strategies to best mimic in-person recruitment. The purpose of this study was to evaluate applicant opinions of the virtual recruitment format. MATERIALS AND METHODS: Postinterview survey responses for applicants interviewing at a single general surgery residency program in the 2020-2021 and 2021-2022 cycles were evaluated. All interviewed applicants were sent an anonymous survey assessing the virtual interview structure, their impression of the program, and their opinions on recruitment in the future. RESULTS: The response rate was 31.2% (n = 60). Most (88.4%) respondents reported a more favorable view of the program after a virtual interview. Factors that were most likely to create a favorable impression were residents (89.6%) and culture (81.0%). 50.8% of applicants favored virtual-only interviews. The majority of applicants (60.3%), however, preferred the virtual interview remain a component of the application process, 34.4% recommended that virtual interviews be used as an initial screen before in-person invites, while 19.0% suggested applicants should interview in-person or virtually without penalty. 62.1% favored capping the number of interviews offered by programs and accepted by applicants. CONCLUSIONS: The virtual interview format for general surgery residency allows applicants to effectively evaluate a residency program. Applicants are in favor of a combination of virtual and in-person interviews in the future. Innovation in the recruitment process, including limiting the number of applications and incorporating virtual events, is supported by applicants.


Assuntos
COVID-19 , Internato e Residência , Humanos , Pandemias , Inquéritos e Questionários
6.
J Surg Educ ; 79(6): 1509-1515, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36030182

RESUMO

OBJECTIVE: There is considerable variability in surgeons' approach to write and obtain informed consent for surgery, particularly among resident trainees. We analyzed differences in procedures and complications described in documented surgical consents for cholecystectomy between residents and attendings. We hypothesized that attending consents would describe more comprehensive procedures and complications than those done by residents. DESIGN: This is a retrospective analysis of 334 patients who underwent cholecystectomy. Charts were queried for demographics, surgical approach, whether the consent was completed electronically, and which provider completed the consent. Specifically, consents were evaluated for inclusion of possible conversion to open procedure, intraoperative cholangiogram, bile duct injury, injury to nearby structures, reoperation, bile leak, as well as if the consent matched the actual procedure performed. SETTING: This study was conducted at an accredited general surgery training program at an academic tertiary care center in the Midwest. PARTICIPANTS: This was a review of 334 patients who underwent cholecystectomy over a 1 year period. RESULTS: Of all documented consents analyzed, 153 (47%) specifically included possible intraoperative cholangiogram, 156 (47%) included bile duct injury, 76 (23%) included injury to nearby structures, 22 (7%) included reoperation, and 62 (19%) included bile leak. In comparing residents and attendings, residents were more likely to consent for bile duct injury (p = 0.002), possible intraoperative cholangiogram (p = 0.0007), injury to nearby structures (p < 0.0001), reoperation (p < 0.0001), and bile leak (p < 0.0001). CONCLUSIONS: Significant variation exists between documentation between resident and attending cholecystectomy consents, with residents including more complications than attendings on their consent forms. These data suggest that experience alone does not predict content of written consents, particularly for common ambulatory procedures. Education regarding the purpose of informed consent and what should be included in one may lead to a reduction in variability between providers.


Assuntos
Traumatismos Abdominais , Colecistectomia , Humanos , Estudos Retrospectivos , Consentimento Livre e Esclarecido , Gestão de Riscos , Documentação
7.
Am J Surg ; 224(5): 1319-1323, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-35781374

RESUMO

BACKGROUND: The benefit of a balanced resuscitation in low volume transfusions remains unclear This study is aimed at characterizing blood product ratios in this cohort. METHODS: A retrospective analysis (2017-2019) of the ACS TQIP was performed to identify adult trauma patients who received ≥1 unit of packed red blood cells (pRBCs) 4 and 24 h after admission. Blood products received were used to calculate plasma and platelet ratios. RESULTS: Plasma and platelet ratios were closer to the target 1:1 ratio for ≤4 units pRBCs. Plasma and platelet ratios increased for those receiving ≤10 units pRBCs, demonstrating increasingly unbalanced resuscitation. Transfusion ratios were unbalanced for those receiving ≥5 units pRBC. CONCLUSION: Transfusion ratios were closer to the desired transfusion ratio for low volume blood product resuscitation. In those receiving ≥5 units pRBC, plasma and platelet ratios were not balanced. The optimal transfusion ratio in low volume trauma resuscitation is unknown.


Assuntos
Transfusão de Sangue , Ferimentos e Lesões , Adulto , Humanos , Estudos Retrospectivos , Ressuscitação , Plasma , Plaquetas , Ferimentos e Lesões/terapia
9.
J Trauma Acute Care Surg ; 93(1): 113-117, 2022 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-35319540

RESUMO

BACKGROUND: Recent studies have shown that nonoperative management of patients with splenic injury has up to a 90% success rate. However, delayed hemorrhage secondary to splenic artery pseudoaneurysm occurs in 5% to 10% of patients with up to 27% of patients developing a pseudoaneurysm on delayed imaging. The goal of our study was to evaluate the safety and utility of delayed computed tomography (CT) imaging for blunt splenic injury patients. METHODS: A retrospective evaluation of all traumatic splenic injuries from 2018 to 2020 at a single level 1 trauma center was undertaken. Patients were subdivided into four groups based on the extent of splenic injury: grades I and II, grade III, grade IV, and grade V. Patient injury characteristics along with hospital length of stay, imaging, procedures, and presence/absence of pseudoaneurysm were documented. RESULTS: A total of 588 trauma patients were initially included for evaluation, with 539 included for final analysis. Two hundred ninety-seven patients sustained grades I and II; 123 patients, grade III; 61 patients, grade IV; and 58 patients, grade V splenic injuries. One hundred twenty-nine patients (24%) underwent either emergent or delayed (>6 hours) splenectomy with an additional six patients having a splenorrhaphy on initial operation. Of the patients who were treated nonoperatively, 98% of grade III, 91% of grade IV, and 100% of grade V splenic injury patients underwent follow-up CT imaging. The mean ± SD time from admission to follow-up abdominal CT scan was 5 ± 4.4 days. Twenty-two pseudoaneurysms were identified including grade III (10 of 84), grade IV (7 of 22), and grade V (2 of 5) patients; of these patients, 33% of grade III and 30% of grade IV required subsequent splenectomy. CONCLUSION: Routine follow-up CT imaging after high-grade splenic injury identifies splenic artery pseudoaneurysm in a significant proportion of patients. Standardized surveillance imaging for high-grade splenic trauma promotes prospective identification of pseudoaneurysms, allowing for interventions to minimize delayed splenic injury complications. LEVEL OF EVIDENCE: Therapeutic/Care Management; level IV.


Assuntos
Traumatismos Abdominais , Falso Aneurisma , Ferimentos não Penetrantes , Traumatismos Abdominais/complicações , Falso Aneurisma/diagnóstico por imagem , Falso Aneurisma/etiologia , Falso Aneurisma/terapia , Humanos , Escala de Gravidade do Ferimento , Estudos Prospectivos , Estudos Retrospectivos , Baço/lesões , Artéria Esplênica/diagnóstico por imagem , Artéria Esplênica/lesões , Ferimentos não Penetrantes/complicações , Ferimentos não Penetrantes/diagnóstico por imagem , Ferimentos não Penetrantes/terapia
10.
Surgery ; 171(3): 833-842, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34974917

RESUMO

BACKGROUND: Massive transfusion with older packed red blood cells is associated with increased morbidity and mortality. As packed red blood cells age, they undergo biochemical and structural changes known as the storage lesion. We developed a novel solution to increase viscosity in stored packed red blood cells. We hypothesized that packed red blood cell storage in this solution would blunt storage lesion formation and mitigate the inflammatory response after resuscitation. METHODS: Blood was obtained from 8- to 10-week-old C57BL/6 male donor mice or human volunteers and stored as packed red blood cell units for 14 days for mice or 42 days for humans in either standard AS-3 storage solution or EAS-1587, the novel packed red blood cell storage solution. Packed red blood cells were analyzed for microvesicles, cell-free hemoglobin, phosphatidylserine, band-3 protein, glucose utilization, and osmotic fragility. Additional mice underwent hemorrhage and resuscitation with packed red blood cells stored in either AS-3 or EAS-1587. Serum was analyzed for inflammatory markers. RESULTS: Murine packed red blood cells stored in EAS-1587 demonstrated reductions in microvesicle and cell-free hemoglobin accumulation as well as preserved band-3 expression, increase glucose utilization, reductions in phosphatidylserine expression, and susceptibility to osmotic stress. Serum from mice resuscitated with packed red blood cells stored in EAS-1587 demonstrated reduced proinflammatory cytokines. Human packed red blood cells demonstrated a reduction in microvesicle and cell-free hemoglobin as well as an increase in glucose utilization. CONCLUSION: Storage of packed red blood cells in a novel storage solution mitigated many aspects of the red blood cell storage lesion as well as the inflammatory response to resuscitation after hemorrhage. This modified storage solution may lead to improvement of packed red blood cell storage and reduce harm after massive transfusion.


Assuntos
Adenina , Preservação de Sangue , Citratos , Eritrócitos , Glucose , Soluções para Preservação de Órgãos , Fosfatos , Choque Hemorrágico/terapia , Cloreto de Sódio , Animais , Soluções Tampão , Modelos Animais de Doenças , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Fatores de Tempo , Viscosidade
11.
J Trauma Acute Care Surg ; 92(2): 266-276, 2022 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-34789700

RESUMO

BACKGROUND: Blunt chest wall injury accounts for 15% of trauma admissions. Previous studies have shown that the number of rib fractures predicts inpatient opioid requirements, raising concerns for pharmacologic consequences, including hypotension, delirium, and opioid dependence. We hypothesized that intercostal injection of liposomal bupivacaine would reduce analgesia needs and improve spirometry metrics in trauma patients with rib fractures. METHODS: A prospective, double-blinded, randomized placebo-control study was conducted at a Level I trauma center as a Food and Drug Administration investigational new drug study. Enrollment criteria included patients 18 years or older admitted to the intensive care unit with blunt chest wall trauma who could not achieve greater than 50% goal inspiratory capacity. Patients were randomized to liposomal bupivacaine or saline injections in up to six intercostal spaces. Primary outcome was to examine pain scores and breakthrough pain medications for 96-hour duration. The secondary endpoint was to evaluate the effects of analgesia on pulmonary physiology. RESULTS: One hundred patients were enrolled, 50 per cohort, with similar demographics (Injury Severity Score, 17.9 bupivacaine 17.6 control) and comorbidities. Enrolled patients had a mean age of 60.5 years, and 47% were female. Rib fracture number, distribution, and targets for injection were similar between groups. While both groups displayed a decrease in opioid use over time, there was no change in mean daily pain scores. The bupivacaine group achieved higher incentive spirometry volumes over Days 1 and 2 (1095 mL, 1063 mL bupivacaine vs. 900 mL, 866 mL control). Hospital and intensive care unit lengths of stay were similar and there were no differences in postinjection pneumonia, use of epidural catheters or adverse events bet ween groups. CONCLUSION: While intercostal liposomal bupivacaine injection is a safe method for rib fracture-related analgesia, it was not effective in reducing pain scores, opioid requirements, or hospital length of stay. Bupivacaine injection transiently improved incentive spirometry volumes, but without a reduction in the development of pneumonia. LEVEL OF EVIDENCE: Therapeutic/care management, Level II.


Assuntos
Anestésicos Locais/administração & dosagem , Bupivacaína/administração & dosagem , Manejo da Dor/métodos , Fraturas das Costelas/complicações , Analgésicos Opioides/uso terapêutico , Método Duplo-Cego , Feminino , Humanos , Injeções , Escala de Gravidade do Ferimento , Unidades de Terapia Intensiva , Tempo de Internação/estatística & dados numéricos , Lipossomos , Masculino , Pessoa de Meia-Idade , Medição da Dor , Estudos Prospectivos , Espirometria
12.
J Surg Res ; 268: 9-16, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34280664

RESUMO

BACKGROUND: Multimodal analgesia protocols have been implemented after elective surgery to reduce opioid use, however there is limited data on utility after polytrauma. Therefore, we investigated the impact of a multimodal analgesia protocol on inpatient and post-discharge outpatient opioid use after polytrauma. METHODS: A retrospective review of patients admitted to a Level I trauma center between September 2017-February 2018 (prior to multimodal protocol; "pre-cohort") and October 2018-April 2019 (after multimodal protocol; "post-cohort") was performed. An outpatient controlled substance registry was utilized to capture morphine milligram equivalents (MME) and gabapentin dispensed in the 6 mo after injury. RESULTS: 620 patients were included (295 pre-cohort, 325 post-cohort). Total inpatient MME decreased from 177.5 mg-130 mg (P= 0.01) between the cohorts. Daily inpatient MME decreased from 70.8 mg-44.7 mg (P< 0.01). Intravenous hydromorphone decreased from 2 mg in the pre-cohort to 1 mg in the post-cohort (P= 0.02). Inpatient oxycodone decreased from 45 mg-30 mg (P= 0.01). Concurrently, gabapentin increased from 0 mg-400 mg in the post-cohort (P< 0.01). Patients in the post-cohort were prescribed fewer MMEs than the pre-cohort at discharge (P< 0.05). However, the number of patients prescribed gabapentin increased from 6.1%-16% (P< 0.01). CONCLUSION: Implementation of an updated multimodal analgesia protocol decreased total MME, daily MME, hydromorphone, and oxycodone consumed while increasing gabapentin use. This suggests that while reducing opioid usage in-hospital is critical to reducing outpatient usage, multimodal pain protocols may lead to an increase in gabapentin prescriptions and utilization after discharge.


Assuntos
Analgesia , Analgésicos Opioides , Assistência ao Convalescente , Analgesia/métodos , Analgésicos Opioides/uso terapêutico , Humanos , Pacientes Internados , Pacientes Ambulatoriais , Dor Pós-Operatória/tratamento farmacológico , Dor Pós-Operatória/etiologia , Alta do Paciente , Estudos Retrospectivos
13.
J Surg Res ; 267: 197-202, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34153562

RESUMO

INTRODUCTION: Thrombocytosis and leukocytosis are common after splenectomy. The potential effect of emergency surgery on these postoperative findings is unknown. We hypothesized that emergency splenectomy leads to a more profound and persistent hematologic change as compared to elective splenectomy. METHODS: A retrospective review was conducted of patients who underwent elective or trauma splenectomy. Records were queried for platelet (PLT) and white blood cell (WBC) count prior to splenectomy, on postoperative days 1-5, and at day 14, 1 month, 3 months, 6 months, and 1 year. Complications, including thromboembolic events, infection, need for repeat operation, and readmission within 30 days of discharge, were recorded. RESULTS: 463 patients were identified as being eligible for the study, with 173 patients in the elective cohort and 145 patients in each of the isolated trauma splenectomy and polytrauma cohorts. Both cohorts had peak thrombocytosis at week 2 postoperatively. However, polytrauma patients had a significantly higher peak platelet count (P < 0.01). The PLT:WBC ratio was lower in both trauma cohorts pre-operatively and postoperative day 1. Trauma splenectomy had a higher PLT:WBC ratio on days 2 and 3 whereas polytrauma had a lower ratio on days 4 and 5. Emergency cases had greater reoperation and infection rates, whereas elective cases were more likely to require readmission. Postoperative thromboembolic events were only higher in the polytrauma cohort. CONCLUSIONS: While trauma splenectomy resulted in more profound postoperative leukocytosis and thrombocytosis, there was no correlation with timing of infection or risk of thromboembolic events. These findings suggest that thrombocytosis and leukocytosis may be associated with thrombotic and infectious events but their presence alone does not indicate direct risks of concomitant infection or thrombosis.


Assuntos
Esplenectomia , Trombocitose , Humanos , Contagem de Leucócitos , Contagem de Plaquetas , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos , Esplenectomia/efeitos adversos , Trombocitose/complicações , Trombocitose/etiologia
14.
Surgery ; 169(3): 666-670, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-32847673

RESUMO

BACKGROUND: Transfusion of blood products is the ideal resuscitative strategy after hemorrhage. Unfortunately, older packed red blood cells have been associated with increased morbidity and mortality after massive transfusion. These packed red blood cells accumulate biochemical and structural changes known as the red blood cell storage lesions. The effect of washing on the formation of red blood cell storage lesions is unknown. We hypothesized that washing packed red blood cells during storage would decrease the development of the red blood cell storage lesions. METHODS: Blood from 8- to 10-week-old male mice donors was stored as packed red blood cells for 14 days. A subset of packed red blood cells were washed with phosphate-buffered saline on storage day 7 and resuspended in AS-1 solution for an additional 7 days as washed packed red blood cells. Subsequently, the packed red blood cells were analyzed for microvesicle release, band-3 erythrocyte membrane integrity protein (Band-3), expression of phosphatidylserine, cell viability (calcein), accumulation of cell-free hemoglobin, and osmotic fragility. RESULTS: In the washed packed red blood cells group, there was less microvesicle accumulation, greater Band-3 expression, less phosphatidylserine expression, a decrease in cell-free hemoglobin accumulation, and a decrease in osmotic fragility, but no differences in red blood cells viability. CONCLUSION: Washing packed red blood cells during storage decreases the accumulation of red blood cell storage lesions. This strategy may lessen the sequelae associated with transfusion of older packed red blood cells.


Assuntos
Transfusão de Eritrócitos , Eritrócitos , Manejo de Espécimes , Animais , Biomarcadores , Micropartículas Derivadas de Células , Criopreservação , Contagem de Eritrócitos , Índices de Eritrócitos , Eritrócitos/metabolismo , Hemoglobinas , Masculino , Camundongos , Fragilidade Osmótica , Manejo de Espécimes/métodos , Fatores de Tempo
15.
Shock ; 55(4): 526-535, 2021 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-32826814

RESUMO

ABSTRACT: Whole blood is a powerful resuscitation strategy for trauma patients but has a shorter shelf life than other blood products. The red blood cell storage lesion in whole blood has not previously been investigated beyond the standard storage period. In the present study, we hypothesized that erythrocytes in stored whole blood exhibit similar aspects of the red blood cell storage lesion and that transfusion of extended storage whole blood would not result in a more severe inflammatory response after hemorrhage in a murine model. To test this hypothesis, we stored low-titer, O-positive, whole blood units, and packed red blood cells (pRBCs) for up to 42 days, then determined aspects of the red blood cell storage lesion. Compared with standard storage pRBCs, whole blood demonstrated decreased microvesicle and free hemoglobin at 21 days of storage and no differences in osmotic fragility. At 42 days of storage, rotational thromboelastometry demonstrated that clotting time was decreased, alpha angle was increased, and clot formation time and maximum clot firmness similar in whole blood as compared with pRBCs with the addition of fresh frozen plasma. In a murine model, extended storage whole blood demonstrated decreased microvesicle formation, phosphatidylserine, and cell-free hemoglobin. After hemorrhage and resuscitation, TNF-a, IL-6, and IL-10 were decreased in mice resuscitated with whole blood. Red blood cell survival was similar at 24 h after transfusion. Taken together, these data suggest that red blood cells within whole blood stored for an extended period of time demonstrate similar or reduced accumulation of the red blood cell storage lesion as compared with pRBCs. Further examination of extended-storage whole blood is warranted.


Assuntos
Preservação de Sangue , Transfusão de Sangue , Eritrócitos , Ressuscitação , Animais , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Fatores de Tempo
16.
Artigo em Inglês | MEDLINE | ID: mdl-33168615

RESUMO

Intravenous (i.v.) minocycline is increasingly used to treat infections caused by multidrug-resistant (MDR) Acinetobacter baumannii Despite its being approved nearly 50 years ago, published information on its pharmacokinetic (PK) profile is limited. This multicenter study examined the PK and probability of pharmacokinetic-pharmacodynamic (PK-PD) target attainment profile of i.v. minocycline in critically ill patients, with suspected or documented infection with Gram-negative bacteria. The PK study population included 55 patients who received a single 200-mg i.v. dose of minocycline. Plasma PK samples were collected predose and 1, 4, 12, 24, 36, and 48 h after initiation of minocycline. Total and unbound minocycline concentrations were determined at each time point. Probabilities of achieving the PK-PD targets associated with stasis and 1-log killing (free area under the curve above the MIC [fAUC:MIC] of 12 and 18, respectively) in an immunocompetent animal pneumonia infection model of A. baumannii were evaluated. A two-compartment population PK model with zero-order i.v. input and first-order elimination, which estimated a constant fraction unbound (fub) for minocycline, best characterized the total and unbound plasma minocycline concentration-time data. The only two covariates retained in the final PK model were body surface area (associated with central volume of distribution) and albumin (associated with fub). In the PK-PD probability of target attainment analyses, minocycline 200 mg i.v. every 12 h (Q12H) was predicted to result in a suboptimal PK-PD profile for patients with A. baumannii infections with MIC values of >1 mg/liter. Like all PK-PD profiling studies of this nature, these findings need clinical confirmation.


Assuntos
Acinetobacter baumannii , Minociclina , Adulto , Animais , Antibacterianos/uso terapêutico , Estado Terminal , Humanos , Testes de Sensibilidade Microbiana
17.
Am J Surg ; 221(5): 987-992, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-32981654

RESUMO

BACKGROUND: Surgical residencies have implemented boot-camps for early acquisition of basic technical skills for interns. However, educators worry that retention is poor. We hypothesized that a structured boot-camp curriculum would improve skills. METHODS: Interns underwent eight boot-camp sessions at the beginning of residency. Interns completed pre-, post-boot-camp, and end-of-year skills assessments, as well as post-boot camp and end-of-year porcine procedure labs. Proficiency was measured on a 5-point scale and by completion time. RESULTS: After boot-camp, interns improved all domains of knot-tying. Median time decreased for skin-closure (8.3 vs 9.9 min, p < 0.01), peg transfer (57 vs 87 s, p < 0.01), intracorporeal (178 vs 300 s, p < 0.01), and extracorporeal knot-tying (140 vs 259 s, p < 0.01). At the end-of-year assessment, interns exhibited retention of all skills and improved in knot-tying and central line skills. During the retention porcine lab, interns progressed basic but not complex skills. CONCLUSIONS: An eight-week boot-camp effectively improved technical skills among surgery interns. Interns retained all skills and improved upon techniques frequently practiced during intern year.


Assuntos
Competência Clínica , Cirurgia Geral/educação , Internato e Residência , Procedimentos Cirúrgicos Operatórios/educação , Cateterismo Venoso Central , Avaliação Educacional , Feminino , Humanos , Internato e Residência/métodos , Internato e Residência/organização & administração , Laparoscopia/educação , Masculino , Retenção Psicológica , Procedimentos Cirúrgicos Operatórios/métodos , Procedimentos Cirúrgicos Operatórios/normas , Técnicas de Sutura/educação , Técnicas de Fechamento de Ferimentos/educação
18.
J Surg Res ; 259: 296-304, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33131764

RESUMO

BACKGROUND: Chronic traumatic encephalopathy is a consequence of repetitive mild traumatic brain injury (rmTBI). These injuries can result in psychiatric disorders that are treated with amitriptyline. Amitriptyline improves neuronal regeneration in major depression via inhibition of acid sphingomyelinase. We hypothesized that acid sphingomyelinase inhibition would preserve neuronal regeneration and decrease depressive symptoms following rmTBI in a murine model. METHODS: A murine model of rmTBI was established using a weight-drop method. Mice were subjected to mTBI every other day for 7 d. Mice received amitriptyline injection 2 h prior to each mTBI. After the final mTBI, mice underwent behavioral studies or biochemical analysis. Hippocampi were analyzed for markers of neurogenesis and phosphorylated tau aggregation. RESULTS: Mice that underwent rmTBI showed increased hippocampal phosphorylated tau aggregation 1 mo following rmTBI as well as decreased neuronal regeneration by bromodeoxyuridine uptake and doublecortin immunohistochemistry. Mice with either genetic deficiency or pharmacologic inhibition of acid sphingomyelinase demonstrated improved neuronal regeneration and decreased phosphorylated tau aggregation compared to untreated rmTBI mice. Behavioral testing showed rmTBI mice spent significantly more time in the dark and waiting to initiate feeding compared to sham mice. These behaviors were partially prevented by the inhibition of acid sphingomyelinase. CONCLUSIONS: We established a murine model of rmTBI that leads to tauopathy, depression, and impaired hippocampal neurogenesis. Inhibition of acid sphingomyelinase prevented the harmful neurologic and behavioral effects of rmTBI. These findings highlight an important opportunity to improve recovery or prevent neuropsychiatric decline in patients at risk for chronic traumatic encephalopathy.


Assuntos
Concussão Encefálica/tratamento farmacológico , Esfingomielina Fosfodiesterase/antagonistas & inibidores , Amitriptilina/uso terapêutico , Animais , Concussão Encefálica/enzimologia , Concussão Encefálica/patologia , Concussão Encefálica/psicologia , Modelos Animais de Doenças , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Agregação Patológica de Proteínas/prevenção & controle , Esfingomielina Fosfodiesterase/fisiologia , Proteínas tau/química
19.
J Surg Res ; 256: 623-628, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32810662

RESUMO

BACKGROUND: Posttraumatic hepatic artery pseudoaneurysm is a potentially devastating complication after complex liver injury. Increasing computed tomography (CT) use may lead to more frequent identification of posttraumatic hepatic complications. This study was designed to determine the rate of hepatic pseudoaneurysm after traumatic liver injury. METHODS: We conducted a retrospective review of patients at an urban level 1 trauma center over 5 y (2012-2016). Injury characteristics, patient management, and complications were extracted from trauma registry data and chart review. RESULTS: Six hundred thirty-four hepatic injuries (11 no grade/no CT, 159 grade I, 154 grade II, 165 grade III, 93 grade IV, and 52 grade V) were identified from our trauma registry. No patient with a grade I or II injury had a subsequent bleeding complication. Eighteen patients had a documented hepatic pseudoaneurysm: grade III n = 3 (1.8%), grade IV n = 6 (6.5%), grade V n = 9 (17.3%). The median time to pseudoaneurysm identification was 6.5 d. Seven pseudoaneurysms were found on asymptomatic surveillance CT-angiography on average 5 d after injury. Eleven patients were symptomatic at the time of CT-angiography performed at a median of 9 d after admission. Of the 11 symptomatic patients, four were in hemorrhagic shock, and two died from hepatic-related complications. CONCLUSIONS: The incidence of hepatic artery pseudoaneurysm increases with higher grade liver injury. Aggressive surveillance for hepatic pseudoaneurysm with interval CT-angiography 5-7 d postinjury may be warranted, especially for grade IV and V injuries.


Assuntos
Falso Aneurisma/epidemiologia , Artéria Hepática/patologia , Fígado/lesões , Choque Hemorrágico/epidemiologia , Ferimentos não Penetrantes/complicações , Adulto , Falso Aneurisma/diagnóstico , Falso Aneurisma/etiologia , Angiografia por Tomografia Computadorizada , Feminino , Artéria Hepática/diagnóstico por imagem , Humanos , Incidência , Escala de Gravidade do Ferimento , Fígado/irrigação sanguínea , Fígado/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Sistema de Registros/estatística & dados numéricos , Estudos Retrospectivos , Choque Hemorrágico/diagnóstico , Choque Hemorrágico/etiologia , Fatores de Tempo , Ferimentos não Penetrantes/diagnóstico , Adulto Jovem
20.
Thromb Res ; 193: 211-217, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32798961

RESUMO

INTRODUCTION: Traumatic brain injury (TBI) induces acute hypocoagulability, subacute hypercoagulability, and persistently elevated risk for thromboembolic events. Splenectomy is associated with increased mortality in patients with moderate or severe TBI. We hypothesized that the adverse effects of splenectomy in TBI patients may be secondary to the exacerbation of pathologic coagulation and platelet activation changes. METHODS: An established murine weight-drop TBI model was utilized and a splenectomy was performed immediately following TBI. Sham as well as TBI and splenectomy alone mice were used as injury controls. Mice were sacrificed for blood draws at 1, 6, and 24 h, as well as 7 days post-TBI. Viscoelastic coagulation parameters were assessed by rotational thromboelastometry (ROTEM) and platelet activation was measured by expression of P-selectin via flow cytometry analysis of platelet rich plasma samples. RESULTS: At 6 h following injury, TBI/splenectomy demonstrated hypocoagulability with prolonged clot formation time (CFT) compared to TBI alone. By 24 h following injury, TBI/splenectomy and splenectomy mice were hypercoagulable with a shorter CFT, a higher alpha angle, and increased MCF, despite a lower percentage of platelet contribution to clot compared to TBI alone. However, only the TBI/splenectomy continued to display this hypercoagulable state at 7 days. While TBI/splenectomy had greater P-selectin expression at 1-h post-injury, TBI alone had significantly greater P-selectin expression at 24 h post-injury compared to TBI/splenectomy. Interestingly, P-selectin expression remained elevated only in TBI/splenectomy at 7 days post-injury. CONCLUSION: Splenectomy following TBI exacerbates changes in the post-injury coagulation state. The combination of TBI and splenectomy induces an acute hypocoagulable state that could contribute to an increase in intracranial bleeding. Subacutely, the addition of splenectomy to TBI exacerbates post-injury hypercoagulability and induces persistent platelet activation. These polytrauma effects on coagulation may contribute to the increased mortality observed in patients with combined brain and splenic injuries.


Assuntos
Transtornos da Coagulação Sanguínea , Esplenectomia , Animais , Modelos Animais de Doenças , Humanos , Camundongos , Ativação Plaquetária , Esplenectomia/efeitos adversos , Tromboelastografia
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