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2.
Perit Dial Int ; 40(2): 132-140, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32063197

RESUMO

BACKGROUND: Peritoneal dialysis (PD)-associated peritonitis carries significant morbidity, mortality, and is a leading cause of PD technique failure. This study aimed to assess the scope and variability of PD-associated peritonitis reported in randomized trials and observational studies. METHODS: Cochrane Controlled Register of Trials, MEDLINE, and Embase were searched from 2007 to June 2018 for randomized trials and observational studies in adult and pediatric patients on PD that reported PD-associated peritonitis as a primary outcome or as a part of composite primary outcome. We assessed the peritonitis definitions used, characteristics of peritonitis, and outcome reporting and analysis. RESULTS: Seventy-seven studies were included, three were randomized trials. Thirty-eight (49%) of the included studies were registry-based observational studies. Twenty-nine percent (n = 22) of the studies did not specify how PD-associated peritonitis was defined. Among those providing a definition of peritonitis, three components were reported: effluent cell count (n = 42, 54%), clinical features consistent with peritonitis (e.g. abdominal pain and/or cloudy dialysis effluent) (n = 35, 45%), and positive effluent culture (n = 19, 25%). Of those components, 1 was required to make the diagnosis in 6 studies (8%), 2 out of 2 were required in 22 studies (29%), 2 out of 3 in 11 studies (14%), and 3 out of 3 in 4 studies (5%). Peritonitis characteristics and outcomes reported across studies included culture-negative peritonitis (n = 47, 61%), refractory peritonitis (n = 42, 55%), repeat peritonitis (n = 9, 12%), relapsing peritonitis (n = 5, 7%), concomitant exit site (n = 16, 21%), and tunnel infections (n = 8, 10%). Peritonitis-related hospitalization was reported in 38% of the studies (n = 29), and peritonitis-related mortality was variably defined and reported in 55% of the studies (n = 42). Peritonitis rate was most frequently reported as episodes per patient year (n = 40, 52%). CONCLUSION: Large variability exists in the definitions, methods of reporting, and analysis of PD-associated peritonitis across trials and observational studies. Standardizing definitions for reporting of peritonitis and associated outcomes will better enable assessment of the comparative effect of interventions on peritonitis. This will facilitate continuous quality improvement measures through reliable benchmarking of this patient-important outcome across centers and countries.

3.
Pediatr Surg Int ; 36(3): 373-381, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31900592

RESUMO

PURPOSE: Venous thromboembolism (VTE) in injured children is rare, but sequelae can be morbid and life-threatening. Recent trauma society guidelines suggesting that all children over 15 years old should receive thromboprophylaxis may result in overtreatment. We sought to evaluate the efficacy of a previously published VTE prediction algorithm and compare it to current recommendations. METHODS: Two institutional trauma registries were queried for all pediatric (age < 18 years) patients admitted from 2007 to 2018. Clinical data were applied to the algorithm and the area under the receiver operating characteristic (AUROC) curve was calculated to test algorithm efficacy. RESULTS: A retrospective review identified 8271 patients with 30 episodes of VTE (0.36%). The VTE prediction algorithm classified 51 (0.6%) as high risk (> 5% risk), 322 (3.9%) as moderate risk (1-5% risk) and 7898 (95.5%) as low risk (< 1% risk). AUROC was 0.93 (95% CI 0.89-0.97). In our population, prophylaxis of the 'moderate-' and 'high-risk' cohorts would outperform the sensitivity (60% vs. 53%) and specificity (96% vs. 77%) of current guidelines while anticoagulating substantially fewer patients (373 vs. 1935, p < 0.001). CONCLUSION: A VTE prediction algorithm using clinical variables can identify injured children at risk for venous thromboembolic disease with more discrimination than current guidelines. Prospective studies are needed to investigate the validity of this model. LEVEL OF EVIDENCE: III-Clinical decision rule evaluated in a single population.

4.
Am J Kidney Dis ; 2020 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-31932094

RESUMO

RATIONALE & OBJECTIVE: Peritoneal dialysis (PD)-related peritonitis carries high morbidity for PD patients. Understanding the characteristics and risk factors for peritonitis can guide regional development of prevention strategies. We describe peritonitis rates and the associations of selected facility practices with peritonitis risk among countries participating in the Peritoneal Dialysis Outcomes and Practice Patterns Study (PDOPPS). STUDY DESIGN: Observational prospective cohort study. SETTING & PARTICIPANTS: 7,051 adult PD patients in 209 facilities across 7 countries (Australia, New Zealand, Canada, Japan, Thailand, United Kingdom, United States). EXPOSURES: Facility characteristics (census count, facility age, nurse to patient ratio) and selected facility practices (use of automated PD, use of icodextrin or biocompatible PD solutions, antibiotic prophylaxis strategies, duration of PD training). OUTCOMES: Peritonitis rate (by country, overall and variation across facilities), microbiology patterns. ANALYTICAL APPROACH: Poisson rate estimation, proportional rate models adjusted for selected patient case-mix variables. RESULTS: 2,272 peritonitis episodes were identified in 7,051 patients (crude rate, 0.28 episodes/patient-year). Facility peritonitis rates were variable within each country and exceeded 0.50/patient-year in 10% of facilities. Overall peritonitis rates, in episodes per patient-year, were 0.40 (95% CI, 0.36-0.46) in Thailand, 0.38 (95% CI, 0.32-0.46) in the United Kingdom, 0.35 (95% CI, 0.30-0.40) in Australia/New Zealand, 0.29 (95% CI, 0.26-0.32) in Canada, 0.27 (95% CI, 0.25-0.30) in Japan, and 0.26 (95% CI, 0.24-0.27) in the United States. The microbiology of peritonitis was similar across countries, except in Thailand, where Gram-negative infections and culture-negative peritonitis were more common. Facility size was positively associated with risk for peritonitis in Japan (rate ratio [RR] per 10 patients, 1.07; 95% CI, 1.04-1.09). Lower peritonitis risk was observed in facilities that had higher automated PD use (RR per 10 percentage points greater, 0.95; 95% CI, 0.91-1.00), facilities that used antibiotics at catheter insertion (RR, 0.83; 95% CI, 0.69-0.99), and facilities with PD training duration of 6 or more (vs <6) days (RR, 0.81; 95% CI, 0.68-0.96). Lower peritonitis risk was seen in facilities that used topical exit-site mupirocin or aminoglycoside ointment, but this association did not achieve conventional levels of statistical significance (RR, 0.79; 95% CI, 0.62-1.01). LIMITATIONS: Sampling variation, selection bias (rate estimates), and residual confounding (associations). CONCLUSIONS: Important international differences exist in the risk for peritonitis that may result from varied and potentially modifiable treatment practices. These findings may inform future guidelines in potentially setting lower maximally acceptable peritonitis rates.

5.
J Trauma Acute Care Surg ; 88(1): 134-140, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31688790

RESUMO

BACKGROUND: Trauma-induced coagulopathy seen on rotational thromboelastometry (ROTEM) is associated with poor outcomes in adults; however, this relationship is poorly understood in the pediatric population. We sought to define thresholds for product-specific transfusion and evaluate the prognostic efficacy of ROTEM in injured children. METHODS: Demographics, ROTEM, and clinical outcomes from severely injured children (age, < 18 years) admitted to a Level I trauma center between 2014 and 2018 were retrospectively analyzed. Receiver operating characteristic curves were plotted and Youden indexes were calculated against the endpoint of packed red blood cell transfusion to identify thresholds for intervention. The ROTEM parameters were compared against the clinical outcomes of mortality or disability at discharge. RESULTS: Ninety subjects were reviewed. Increased tissue factor-triggered extrinsic pathway (EXTEM) clotting time (CT) >84.5 sec (p = 0.049), decreased EXTEM amplitude at 10 minutes (A10) <43.5 mm (p = 0.025), and decreased EXTEM maximal clot firmness (MCF) <64.5 mm (p = 0.026) were associated with need for blood product transfusion. Additionally, EXTEM CT longer than 68.5 seconds was associated with mortality or disability at discharge. CONCLUSION: Coagulation dysregulation on thromboelastometry is associated with disability and mortality in children. Based on our findings, we propose ROTEM thresholds: plasma transfusion for EXTEM CT longer than 84.5 seconds, fibrinogen replacement for EXTEM A10 less than 43.5 mm, and platelet transfusion for EXTEM MCF less than 64.5 mm. LEVEL OF EVIDENCE: Prognostic, Level III; Therapeutic, Level IV.

6.
J Trauma Acute Care Surg ; 88(2): 279-285, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31738314

RESUMO

BACKGROUND: Trauma-induced coagulopathy is a major driver of mortality following severe injury. Viscoelastic goal-directed resuscitation can reduce mortality after injury. The TEG 5000 system is widely used for viscoelastic testing. However, the TEG 6s system incorporates newer technology, with encouraging results in cardiovascular interventions. The purpose of this study was to validate the TEG 6s system for use in trauma patients. METHODS: Multicenter noninvasive observational study for method comparison conducted at 12 US Levels I and II trauma centers. Agreement between the TEG 6s and TEG 5000 systems was examined using citrated kaolin reaction time (CK.R), citrated functional fibrinogen maximum amplitude (CFF.MA), citrated kaolin percent clot lysis at 30 minutes (CK.LY30), citrated RapidTEG maximum amplitude (CRT.MA), and citrated kaolin maximum amplitude (CK.MA) parameters in adults meeting full or limited trauma team criteria. Blood was drawn ≤1 hour after admission. Assays were repeated in duplicate. Reliability (TEG 5000 vs. TEG 6s analyzers) and repeatability (interdevice comparison) was quantified. Linear regression was used to define the relationship between TEG 6s and TEG 5000 devices. RESULTS: A total of 475 patients were enrolled. The cohort was predominantly male (68.6%) with a median age of 49 years. Regression line slope estimates (ß) and linear correlation estimates (p) were as follows: CK.R (ß = 1.05, ρ = 0.9), CFF.MA (ß = 0.99, ρ = 0.95), CK.LY30 (ß = 1.01, ρ = 0.91), CRT.MA (TEG 6s) versus CK.MA (TEG 5000) (ß = 1.06, ρ = 0.86) as well as versus CRT.MA (TEG 5000) (ß = 0.93, ρ = 0.93), indicating strong reliability between the devices. Overall, within-device repeatability was better for TEG 6s versus TEG 5000, particularly for CFF.MA and CK.LY30. CONCLUSION: The TEG 6s device appears to be highly reliable for use in trauma patients, with close correlation to the TEG 5000 device and equivalent/improved within-device reliability. Given the potential advantages of using the TEG 6s device at the site of care, confirmation of agreement between the devices represents an important advance in diagnostic testing. LEVEL OF EVIDENCE: Diagnostic test, level II.


Assuntos
Transtornos da Coagulação Sanguínea/diagnóstico , Sistemas Automatizados de Assistência Junto ao Leito , Tromboelastografia/instrumentação , Ferimentos e Lesões/complicações , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Transtornos da Coagulação Sanguínea/sangue , Transtornos da Coagulação Sanguínea/etiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Ferimentos e Lesões/sangue , Adulto Jovem
7.
Perit Dial Int ; 39(6): 539-546, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31582465

RESUMO

Background:The optimal treatment for managing anemia in peritoneal dialysis (PD) patients and best clinical practices are not completely understood. We sought to characterize international variations in anemia measures and management among PD patients.Methods:The Peritoneal Dialysis Outcomes and Practice Patterns Study (PDOPPS) enrolled adult PD patients from 6 countries from 2014 to 2017. Hemoglobin (Hb), ferritin levels, and transferrin saturation (TSAT), as well as erythropoiesis stimulating agents (ESAs) and iron use were compared cross-sectionally at study enrollment in Australia and New Zealand (A/NZ), Canada, Japan, the United Kingdom (UK), and the United States (US).Results:Among 3,603 PD patients from 193 facilities, mean Hb ranged from 11.0 - 11.3 g/dL across countries. The majority of patients (range 53% - 59%) had Hb 10 - 11.9 g/dL, with 4% - 12% patients ≥ 13 g/dL and 16% - 23% < 10 g/dL. Use of ESAs was higher in Japan (94% of patients) than elsewhere (66% - 79% of patients). In the US, 63% of patients had a ferritin level > 500 ng/mL, compared with 5% - 38% in other countries. In the US and Japan, 87% - 89% of PD patients had TSAT ≥ 20%, compared with 73% - 76% in other countries. Intravenous (IV) iron use within 4 months of enrollment was higher in the US (55% of patients) than elsewhere (6% - 17% patients).Conclusions:In this largest international observational study of anemia and anemia management in patients receiving PD, comparable Hb levels across countries were observed but with notable differences in ESA and iron use. Peritoneal dialysis patients in the US have higher ferritin levels and higher IV iron use than other countries.

8.
J Neurotrauma ; 2019 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-31382848

RESUMO

Progression of intracranial hemorrhage (PICH) is a significant cause of secondary brain injury in patients with traumatic brain injury (TBI). Previous studies have implicated a variety of mediators that contribute to PICH. We hypothesized that patients with PICH would display either a hypocoagulable state, hyperfibrinolysis, or both. We conducted a prospective study of adult trauma patients with isolated TBI. Blood was obtained for routine coagulation assays, platelet count, fibrinogen, thrombelastography, markers of thrombin generation, and markers of fibrinolysis at admission and 6, 12, 24, and 48 hours. Univariate analyses were performed to compare baseline characteristics between groups. Linear regression models were created, adjusting for baseline differences, to determine the relationship between individual assays and PICH. 141 patients met entry criteria, of whom 71 had hemorrhage progression. Patients with PICH had a higher Injury Severity Score and Abbreviated Injury Scale score (head), a lower Glasgow Coma Scale score, and lower plasma sodium on admission. Patients with PICH had higher D-dimers on admission. After adjusting for baseline differences, elevated D-dimers remained significantly associated with PICH compared to patients without PICH at admission. Hypocoagulation was not significantly associated with PICH in these patients. The association between PICH and elevated D-dimers early after injury suggests that fibrinolytic activation may contribute to PICH in patients with TBI.

10.
J Trauma Acute Care Surg ; 87(1): 117-124, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31260426

RESUMO

BACKGROUND: Hemodynamically unstable patients with severe pelvic fracture are a significant challenge to trauma surgeons and have high mortality. Significant variability across institutions in hemorrhage control adjuncts used to quell pelvic bleeding has been demonstrated. However, the effect of these methods on time to definitive bleeding control, type of resuscitation given, and outcomes remains unknown. We sought to elucidate those effects. METHODS: This was a multicenter retrospective review of severe pelvic fracture patients in shock between 2011 and 2016. Shock was defined as systolic blood pressure less than 90 mm Hg, heart rate greater than 120 beats per minute, or base deficit less than -5. Definitive bleeding control was defined as time to surgical control in the operating room or embolization by interventional radiology. Significance level was at p less than 0.05. RESULTS: A total of 279 severe pelvic fracture patients with shock on admission from 12 trauma centers were included. The cohort was primarily male (62%) with median (interquartile range) age of 40 years (28-54 years), Injury Severity Score of 38 (29-50), and Glasgow Coma Scale score of 13 (3-15). Overall mortality was 32%. The most common adjunct used was pelvic binder (50%) followed by no adjunct (30.5%); least common was resuscitative balloon occlusion of the aorta (REBOA) (2.5%). Preperitoneal packing alone and REBOA alone/with other adjunct(s) resulted in the fastest times to operating room/interventional radiology but also had the highest blood utilization and mortality rates. Resuscitative balloon occlusion of the aorta was most often used along with pelvic binder (6 of 13; 46%). CONCLUSION: Marked variation in management of severe pelvic fracture patients in shock indicates the need for a standardized approach to maximize outcomes and minimize transfusion requirements. The use of preperitoneal packing and/or REBOA yielded fastest times to definitive bleeding control. However, REBOA continues to be infrequently used. Future prospective analysis of this combination needs further validation in patients with severe pelvic hemorrhage. LEVEL OF EVIDENCE: Therapeutic study, level IV.


Assuntos
Fraturas Ósseas/complicações , Ossos Pélvicos/lesões , Choque Hemorrágico/terapia , Adulto , Feminino , Fraturas Ósseas/terapia , Técnicas Hemostáticas/estatística & dados numéricos , Humanos , Escala de Gravidade do Ferimento , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Choque Hemorrágico/etiologia , Centros de Traumatologia/estatística & dados numéricos , Resultado do Tratamento
11.
J Trauma Acute Care Surg ; 87(2): 342-349, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31349348

RESUMO

BACKDROP: Clinicians intuitively recognize that faster time to hemostasis is important in bleeding trauma patients, but these times are rarely reported. METHODS: Prospectively collected data from the Pragmatic Randomized Optimal Platelet and Plasma Ratios trial were analyzed. Hemostasis was predefined as no intraoperative bleeding requiring intervention in the surgical field or resolution of contrast blush on interventional radiology (IR). Patients who underwent an emergent (within 90 minutes) operating room (OR) or IR procedure were included. Mixed-effects Poisson regression with robust error variance (controlling for age, Injury Severity Score, treatment arm, injury mechanism, base excess on admission [missing values estimated by multiple imputation], and time to OR/IR as fixed effects and study site as a random effect) with modified Bonferroni corrections tested the hypothesis that decreased time to hemostasis was associated with decreased mortality and decreased incidence of acute kidney injury (AKI), acute respiratory distress syndrome (ARDS), multiple-organ failure (MOF), sepsis, and venous thromboembolism. RESULTS: Of 680 enrolled patients, 468 (69%) underwent an emergent procedure. Patients with decreased time to hemostasis were less severely injured, had less deranged base excess on admission, and lower incidence of blunt trauma (all p < 0.05). In 408 (87%) patients in whom hemostasis was achieved, every 15-minute decrease in time to hemostasis was associated with decreased 30-day mortality (RR, 0.97; 95% confidence interval [CI], 0.94-0.99), AKI (RR, 0.97; 95% CI, 0.96-0.98), ARDS (RR, 0.98; 95% CI, 0.97-0.99), MOF (RR, 0.94; 95% CI, 0.91-0.97), and sepsis (RR, 0.98; 95% CI, 0.96-0.99), but not venous thromboembolism (RR, 0.99; 95% CI, 0.96-1.03). CONCLUSION: Earlier time to hemostasis was independently associated with decreased incidence of 30-day mortality, AKI, ARDS, MOF, and sepsis in bleeding trauma patients. Time to hemostasis should be considered as an endpoint in trauma studies and as a potential quality indicator. LEVEL OF EVIDENCE: Therapeutic/care management, level III.


Assuntos
Hemorragia/terapia , Técnicas Hemostáticas/mortalidade , Ferimentos e Lesões/terapia , Adulto , Hemorragia/sangue , Hemorragia/mortalidade , Humanos , Escala de Gravidade do Ferimento , Pessoa de Meia-Idade , Transfusão de Plaquetas/métodos , Distribuição de Poisson , Indicadores de Qualidade em Assistência à Saúde , Ressuscitação/métodos , Fatores de Tempo , Ferimentos e Lesões/sangue , Ferimentos e Lesões/mortalidade , Adulto Jovem
13.
Pediatr Nephrol ; 34(10): 1799-1809, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31218394

RESUMO

BACKGROUND: Hypoalbuminemia is a strong predictor of hospitalization and mortality among adult dialysis patients. However, data are scant on the association between serum albumin and hospitalization among children new to dialysis. METHODS: In a retrospective cohort study of children 1-17 years old with end-stage renal disease receiving dialysis therapy in a large US dialysis organization 2007-2011, we examined the association of serum albumin with hospitalization frequency and total hospitalization days using a negative binomial regression model. RESULTS: Among 416 eligible patients, median (interquartile range) age was 14 (10-16) years and mean ± SD baseline serum albumin level was 3.7 ± 0.8 g/dL. Two hundred sixty-six patients (64%) were hospitalized during follow-up with an incidence rate of 2.2 (95%CI, 1.9-2.4) admissions per patient-year. There was a U-shaped association between serum albumin and hospitalization frequency; hospitalization rates (95%CI) were 2.7 (2.2-3.2), 1.9 (1.5-2.4), 1.6 (1.3-1.9), and 2.7 (1.7-3.6) per patient-year among patients with serum albumin levels < 3.5, 3.5- < 4.0, 4.0- < 4.5, and ≥ 4.5 g/dL, respectively. Case mix-adjusted hospitalization incidence rate ratios (IRRs) (95%CI) were 1.63 (1.24-2.13), 1.32 (1.10-1.58), and 1.25 (1.06-1.49) at serum albumin levels 3.0, 3.5, and 4.5 g/dL, respectively (reference: 4.0 g/dL). Similar trends were observed in hospitalization days. These associations remained robust against further adjustment for laboratory variables associated with malnutrition and inflammation. CONCLUSIONS: Both high and low serum albumin were associated with higher hospitalization in children starting dialysis. Because the observed association is novel and not fully explainable especially for high serum albumin levels, interpreting the results requires caution and further studies are needed to confirm and elucidate this association before clinical recommendations are made.

14.
Surgery ; 166(3): 416-422, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31230842

RESUMO

BACKGROUND: Factors predicting timing of post-traumatic venous thromboembolism (VTE) remain incompletely understood. Because the balance between hemorrhage and thrombosis is dynamic during a patient's hospital course, early and late VTE may be physiologically discrete processes. This secondary analysis of the Pragmatic, Randomized Optimal Platelet and Plasma Ratios (PROPPR) trial aims to explore whether certain risk factors are associated with early versus late VTE. METHODS: The PROPPR trial investigated post-traumatic resuscitation with platelets, plasma, and red blood cells in a 1:1:1 ratio compared with a 1:1:2 ratio. Multinomial regression based on a threshold determined by cubic spline analysis tested the association of clinical variables with early or late VTE, a composite of deep vein thrombosis and pulmonary embolus, adjusting for predetermined confounders. RESULTS: Of the 87 patients (13%) with VTE, pulmonary embolus was predominant in the first 72 hours. A statistically determined threshold at 12 days corresponded to change in odds of early versus late events. Variables associated with early VTE included plasma transfusion (risk ratio [RR] 1.14; 95% confidence interval, 1.00, 1.30; P = .05), sepsis (RR 0.05; 95% confidence interval, 1.40, 6.64; P = .01), pelvic or femur fracture (RR 2.62; 95% confidence interval, 1.00, 6.90; P = .05). Late VTE was associated with dialysis (RR 7.37; 95% confidence interval, 1.59, 34.14; P = .01), older age (RR 1.02; 95% confidence interval 1.00, 1.04; P = .05), and delayed resuscitation approaching ratios of 1:1:1 among patients randomized to 1:1:2 therapy (RR 2.06; 95% confidence interval, 0.28, 3.83; P = .02). Cyroprecipitate increased risk of early (RR 1.04, 95% confidence interval, 1.00,1.08; P < .03) and late VTE (1.05; 95% confidence interval, 1.01, 1.09; P = .01). Prolonged lagtime (coeffcient 0.06, 95% confidence interval, 0.02, 0.10; P < .01) and time-to-peak thrombin generation (coeffcient 0.04, 95% confidence interval, 0.02, 0.07; P < .01) were associated with increased risk of early VTE. CONCLUSION: Early and late VTE may differ in their risk factors. Defining temporal trends in VTE may allow for a more individualized approach to thromboprophylaxis.


Assuntos
Tromboembolia Venosa/diagnóstico , Adulto , Coagulação Sanguínea , Transfusão de Componentes Sanguíneos , Ensaios Clínicos como Assunto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Multicêntricos como Assunto , Prognóstico , Ensaios Clínicos Controlados Aleatórios como Assunto , Ressuscitação , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Tromboembolia Venosa/sangue , Tromboembolia Venosa/prevenção & controle , Tromboembolia Venosa/terapia , Adulto Jovem
15.
J Trauma Acute Care Surg ; 87(1S Suppl 1): S14-S21, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31246901

RESUMO

BACKGROUND: The US Military has achieved the highest casualty survival rates in its history. However, there remain multiple areas in combat trauma that present challenges to the delivery of high-quality and effective trauma care. Previous work has identified research priorities for pre-hospital care, but there has been no similar analysis for forward surgical care. METHODS: A list of critical "focus areas" was developed by the Committee on Surgical Combat Casualty Care (CoSCCC). Individual topics were solicited and mapped to appropriate focus areas by group consensus and review of Eastern Association for the Surgery of Trauma (EAST) and Joint Trauma System guidelines. A web-based survey was distributed to the CoSCCC and the military committees of EAST and the American Association for the Surgery of Trauma. Topics were rated on a Likert scale from 1 (low) to 10 (high priority). Descriptives, univariate statistics, and inter-rater correlation analysis was performed. RESULTS: 13 research focus areas were identified (eight clinical and five adjunctive categories). Ninety individual topics were solicited. The survey received 64 responses. The majority of respondents were military (90%) versus civilians (10%). There was moderate to high agreement (inter-rater correlation coefficient = 0.93, p < 0.01) for 10 focus areas. The top five focus areas were Personnel/Staffing (mean, 8.03), Resuscitation and Hemorrhage Management (7.49), Pain/Sedation/Anxiety Management (6.96), Operative Interventions (6.9), and Initial Evaluation (6.9). The "Top 10" research priorities included four in Personnel/Staffing, four in Resuscitation/Hemorrhage Management, and three in Operative Interventions. A complete list of the topics/scores will be presented. CONCLUSIONS: This is the first objective ranking of research priorities for combat trauma care. The "Top 10" priorities were all from three focus areas, supporting prioritization of personnel/staffing of austere teams, resuscitation/hemorrhage control, and damage-control interventions. This data will help guide Department of Defense research programs and new areas for prioritized funding of both military and civilian researchers. LEVEL OF EVIDENCE: Study design, level IV.

16.
J Trauma Acute Care Surg ; 86(6): 931-942, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31124890

RESUMO

BACKGROUND: Platelet (Plt)-derived extracellular vesicles (Plt-EVs) have hemostatic properties similar to Plts. In addition to hemostasis, Plts also function to stabilize the vasculature and maintain endothelial cell (EC) barrier integrity. We hypothesized that Plt-EVs would inhibit vascular EC permeability, similar to fresh Plts. To investigate this hypothesis, we used in vitro and in vivo models of vascular endothelial compromise and bleeding. METHODS: In the vitro model, Plt-EVs were isolated by ultracentrifugation and characterized for Plt markers and particle size distribution. Effects of Plts and Plt-EVs on endothelial barrier function were assessed by transendothelial electrical resistance measurements and histological analysis of endothelial junction proteins. Hemostatic potential of Plt-EVs and Plts was assessed by multiple electrode Plt aggregometry. Using an in vivo model, the effects of Plts and Plt-EVs on vascular permeability and bleeding were assessed in non-obese diabetic-severe combined immunodeficient (NOD-SCID) mice by an established Miles assay of vascular permeability and a tail snip bleeding assay. RESULTS: In the in vitro model, Plt-EVs displayed exosomal size distribution and expressed Plt-specific surface markers. Platelets and Plt-EVs decreased EC permeability and restored EC junctions after thrombin challenge. Multiplate aggregometry revealed that Plt-EVs enhanced thrombin receptor-activating peptide-mediated aggregation of whole blood, whereas Plts enhanced thrombin receptor-activating peptide-, arachidonic acid-, collagen-, and adenosine diphosphate-mediated aggregation. In the in vivo model, Plt-EVs are equivalent to Plts in attenuating vascular endothelial growth factor (VEGF)-A-induced vascular permeability and uncontrolled blood loss in a tail snip hemorrhage model. CONCLUSION: Our study is the first to report that Plt-EVs might provide a feasible product for transfusion in trauma patients to attenuate bleeding, inhibit vascular permeability, and mitigate the endotheliopathy of trauma.

17.
J Transl Med ; 17(1): 128, 2019 04 17.
Artigo em Inglês | MEDLINE | ID: mdl-30995929

RESUMO

BACKGROUND: Cell based therapies, such as bone marrow derived mesenchymal stem cells (BM-MSCs; also known as mesenchymal stromal cells), are currently under investigation for a number of disease applications. The current challenge facing the field is maintaining the consistency and quality of cells especially for cell dose production for pre-clinical testing and clinical trials. Here we determine how BM-donor variability and thus the derived MSCs factor into selection of the optimal primary cell lineage for cell production and testing in a pre-clinical swine model of trauma induced acute respiratory distress syndrome. METHODS: We harvested bone marrow and generated three different primary BM-MSCs from Yorkshire swine. Cells from these three donors were characterized based on (a) phenotype (morphology, differentiation capacity and flow cytometry), (b) in vitro growth kinetics and metabolic activity, and (c) functional analysis based on inhibition of lung endothelial cell permeability. RESULTS: Cells from each swine donor exhibited varied morphology, growth rate, and doubling times. All expressed the same magnitude of standard MSC cell surface markers by flow cytometry and had similar differentiation potential. Metabolic activity and growth potential at each of the passages varied between the three primary cell cultures. More importantly, the functional potency of the MSCs on inhibition of endothelial permeability was also cell donor dependent. CONCLUSION: This study suggests that for production of MSCs for cell-based therapy, it is imperative to examine donor variability and characterize derived MSCs for marker expression, growth and differentiation characteristics and testing potency in application dependent assays prior to selection of the optimal cell lineage for large scale expansion and dose production.

18.
Am J Surg ; 217(5): 970-973, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30935666

RESUMO

INTRODUCTION: Laparoscopic common bile duct exploration (LCBDE-LC) or ERCP plus laparoscopic cholecystectomy (ERCP-LC) represent minimally invasive choledocholithiasis treatments. We hypothesized that LCBDE-LC has a shorter length of stay (LOS) and lower charges than ERCP-LC. METHODS: Charts were reviewed for all LCBDE-LC or ERCP-LC for choledocholithiasis from 2007 to 2017. Exclusions included cholangitis, concomitant procedures, or history of Roux-en-Y or biliary surgery. Groups were determined via intention-to-treat with LCBDE-LC or ERCP-LC. RESULTS: 281 subjects were identified; 157 met inclusion criteria. 89 (56%) were in the LCBDE-LC group. There were no differences in age, sex, or ASA. LOS was shorter for LCBDE-LC (3.1 vs 4.4 days, p < 0.01) although total anesthesia time was longer (292 vs 262 min, p = 0.01). There was no difference in total charges ($44,412 vs $51,353, p = 0.08). Thirty (33%) LCBDE-LC were aborted due to challenges passing the dilator or scope (33%) or clearing stones (30%). Two ERCP-LC cases required post-procedure LCBDE. CONCLUSION: LCBDE-LC resulted in shorter LOS but had a high failure rate. Further research is needed to predict which cases suit each modality.


Assuntos
Colangiopancreatografia Retrógrada Endoscópica/economia , Colecistectomia Laparoscópica/economia , Coledocolitíase/cirurgia , Tempo de Internação/estatística & dados numéricos , Adulto , Anestesia/estatística & dados numéricos , Feminino , Preços Hospitalares/estatística & dados numéricos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Tempo
19.
Am J Surg ; 217(5): 868-872, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30826005

RESUMO

INTRODUCTION: Alcohol consumption has been shown to alter coagulation. However, thromboelastography with platelet mapping (TEG PM) to evaluate platelet function has not been studied. METHODS: A prospective, non-randomized study of healthy volunteers was conducted. Baseline TEG PM were collected. Subjects consumed alcoholic or non-alcoholic beverages for 2 h. Repeat TEG PM was collected. RESULTS: Fifty-four volunteers entered either the experimental group (EG, 17 women and 16 men) or control group (CG, 11 women and 10 men). After 2 h of alcohol or non-alcoholic drink consumption the median breath alcohol level was 0.08 [IQR 0.05, 0.12] in the EG and 0.00 in the CG. After consumption of alcohol, male EG subjects demonstrated higher median Adenosine Diphosphate (ADP) inhibition of platelet function (15.7% [3.9, 39.3] vs 8.2% [0, 30.1), p = 0.035), but female subjects did not. There was no evidence of increased arachidonic acid (AA) platelet inhibition in the EG compared to CG. Clot strength (TEG maximum amplitude) was not different between groups. CONCLUSION: After consumption of alcohol, healthy male volunteers demonstrate ADP platelet inhibition by TEG PM.


Assuntos
Consumo de Bebidas Alcoólicas , Plaquetas/efeitos dos fármacos , Testes de Função Plaquetária , Difosfato de Adenosina/farmacologia , Adulto , Estudos de Casos e Controles , Feminino , Voluntários Saudáveis , Humanos , Masculino , Estudos Prospectivos , Tromboelastografia
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