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1.
Eur J Orthop Surg Traumatol ; 34(5): 2773-2778, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38771369

ABSTRACT

PURPOSE: Determine if anterior internal versus supra-acetabular external fixation of unstable pelvic fractures is associated with care needs or discharge. METHODS: A retrospective cohort study was performed at two tertiary trauma referral centers. Adults with unstable pelvis fractures (AO/OTA 61B/61C) who received operative fixation of the anterior and posterior pelvic ring by two orthopedic trauma surgeons from October 2020 to November 2022 were included. The primary outcome was discharge destination. Secondary outcomes included intensive care unit (ICU) or ventilator days, length of stay, and hospital charges. RESULTS: Eighty-three eligible patients were 38.6% female, with a mean age of 47.2 Ā± 20.3Ā years and BMI 28.1 Ā± 6.4Ā kg/m2. Fifty-nine patients (71.1%) received anterior pelvis internal fixation and 24 (28.9%) received external fixation. External fixation was associated with weight-bearing restrictions (91.7% versus 49.2%, p = 0.01). No differences in demographic, functional status, insurance type, fracture classification, or injury severity measures were observed by treatment. Internal versus external anterior pelvic fixation was not associated with discharge to home (49.2% versus 29.2%, p = 0.10), median ICU days (3.0 [interquartile range (IQR) 7.8 versus 5.5 [IQR 4.3], p = 0.14, ventilator days (0 [IQR 6.0] versus 0 [IQR 2.8], p = 0.51), length of stay (13.0 [IQR 13.0] versus 17.5 (IQR 20.5), p = 0.38), or total hospital charges (US dollars 180,311 [IQR 219,061.75] versus 243,622 [IQR 187,111], p = 0.14). CONCLUSIONS: Anterior internal versus supra-acetabular external fixation of unstable pelvis fractures was not significantly associated with discharge destination, critical care, hospital length of stay, or hospital charges. This sample may be underpowered to detect differences between groups. LEVEL OF EVIDENCE: Therapeutic Level IV.


Subject(s)
Critical Care , Fracture Fixation, Internal , Fracture Fixation , Fractures, Bone , Hospital Charges , Length of Stay , Patient Discharge , Pelvic Bones , Humans , Female , Length of Stay/statistics & numerical data , Middle Aged , Male , Retrospective Studies , Patient Discharge/statistics & numerical data , Pelvic Bones/injuries , Hospital Charges/statistics & numerical data , Fractures, Bone/surgery , Fracture Fixation, Internal/economics , Fracture Fixation, Internal/methods , Critical Care/economics , Critical Care/statistics & numerical data , Fracture Fixation/methods , Fracture Fixation/economics , Adult
2.
Hum Mol Genet ; 30(23): 2215-2224, 2021 11 16.
Article in English | MEDLINE | ID: mdl-34230955

ABSTRACT

CHARGE syndrome is an autosomal dominant malformation disorder caused by pathogenic variants in the chromatin remodeler CHD7. Affected are craniofacial structures, cranial nerves and multiple organ systems. Depending on the combination of malformations present, its distinction from other congenital disorders can be challenging. To gain a better insight into the regulatory disturbances in CHARGE syndrome, we performed RNA-Seq analysis on blood samples of 19 children with CHARGE syndrome and a confirmed disease-causing CHD7 variant in comparison with healthy control children. Our analysis revealed a distinct CHARGE syndrome pattern with downregulation of genes that are linked to disorders described to mimic the CHARGE phenotype, i.e. KMT2D and KDM6A (Kabuki syndrome), EP300 and CREBBP (Rubinstein-Taybi syndrome) and ARID1A and ARID1B (Coffin-Siris syndrome). Furthermore, by performing protein-protein interaction studies using co-immunoprecipitation, direct yeast-two hybrid and in situ proximity ligation assays, we could demonstrate an interplay between CHD7, KMT2D, KDM6A and EP300. In summary, our data demonstrate a mechanistic and regulatory link between the developmental disorders CHARGE-, Kabuki- and Rubinstein Taybi-syndrome providing an explanation for the overlapping phenotypes.


Subject(s)
CHARGE Syndrome/diagnosis , CHARGE Syndrome/genetics , Genetic Association Studies , Genetic Diseases, Inborn/diagnosis , Genetic Diseases, Inborn/genetics , Genetic Predisposition to Disease , Age Factors , CHARGE Syndrome/metabolism , Carrier Proteins , DNA Helicases/genetics , DNA Helicases/metabolism , DNA-Binding Proteins/genetics , DNA-Binding Proteins/metabolism , Gene Expression Profiling , Genetic Association Studies/methods , Genetic Diseases, Inborn/metabolism , Genetic Markers , Genetic Variation , Humans , Immunoprecipitation , Mutation , Neoplasm Proteins/genetics , Neoplasm Proteins/metabolism , Phenotype , Protein Binding , RNA-Seq
3.
PLoS Genet ; 16(1): e1008588, 2020 01.
Article in English | MEDLINE | ID: mdl-31929563

ABSTRACT

Prostate embryonic development, pubertal and adult growth, maintenance, and regeneration are regulated through androgen signaling-mediated mesenchymal-epithelial interactions. Specifically, the essential role of mesenchymal androgen signaling in the development of prostate epithelium has been observed for over 30 years. However, the identity of the mesenchymal cells responsible for this paracrine regulation and related mechanisms are still unknown. Here, we provide the first demonstration of an indispensable role of the androgen receptor (AR) in sonic hedgehog (SHH) responsive Gli1-expressing cells, in regulating prostate development, growth, and regeneration. Selective deletion of AR expression in Gli1-expressing cells during embryogenesis disrupts prostatic budding and impairs prostate development and formation. Tissue recombination assays showed that urogenital mesenchyme (UGM) containing AR-deficient mesenchymal Gli1-expressing cells combined with wildtype urogenital epithelium (UGE) failed to develop normal prostate tissue in the presence of androgens, revealing the decisive role of AR in mesenchymal SHH responsive cells in prostate development. Prepubescent deletion of AR expression in Gli1-expressing cells resulted in severe impairment of androgen-induced prostate growth and regeneration. RNA-sequencing analysis showed significant alterations in signaling pathways related to prostate development, stem cells, and organ morphogenesis in AR-deficient Gli1-expressing cells. Among these altered pathways, the transforming growth factor Ɵ1 (TGFƟ1) pathway was up-regulated in AR-deficient Gli1-expressing cells. We further demonstrated the activation of TGFƟ1 signaling in AR-deleted prostatic Gli1-expressing cells, which inhibits prostate epithelium growth through paracrine regulation. These data demonstrate a novel role of the AR in the Gli1-expressing cellular niche for regulating prostatic cell fate, morphogenesis, and renewal, and elucidate the mechanism by which mesenchymal androgen-signaling through SHH-responsive cells elicits the growth and regeneration of prostate epithelium.


Subject(s)
Hedgehog Proteins/metabolism , Morphogenesis , Prostate/metabolism , Receptors, Androgen/metabolism , Regeneration , Signal Transduction , Animals , Cells, Cultured , Epithelial Cells/cytology , Epithelial Cells/metabolism , Male , Mesenchymal Stem Cells/cytology , Mesenchymal Stem Cells/metabolism , Mice , Prostate/cytology , Prostate/growth & development , Prostate/physiology , Transforming Growth Factor beta/metabolism , Zinc Finger Protein GLI1/genetics , Zinc Finger Protein GLI1/metabolism
4.
Surgeon ; 21(2): 135-139, 2023 Apr.
Article in English | MEDLINE | ID: mdl-35545497

ABSTRACT

BACKGROUND: Prior institutional data have demonstrated trauma mortality to be highest between 06:00-07:59 at our center, which is also when providers change shifts (07:00-07:30). The objective was definition of patient, provider, and systems variables associated with trauma mortality at shift change among patients arriving as trauma team activations (TTA). METHODS: All TTA patients at our ACS-verified Level I trauma center were included (01/2008-07/2019), excluding those with undocumented arrival time. Study groups were defined by arrival time: shift change (SC) (06:00-07:59) vs. non-shift change (NSC) (all other times). Univariable/multivariable analyses compared key variables. Propensity score analysis compared outcomes after matching. RESULTS: After exclusions, 6020 patients remained: 229 (4%) SC and 5791 (96%) NSC. SC mortality was 25% vs. 16% during NSC (pĀ <Ā 0.001). More SC patients arrived with SBP <90 (19% vs. 11%, pĀ <Ā 0.001) or GCS <9 (35% vs. 24%, pĀ <Ā 0.001). ISS was higher during SC (43[32-50] vs. 34[27-50], pĀ <Ā 0.001). Time to CT scan (36[23-66] vs. 38[23-61] minutes, pĀ =Ā 0.638) and emergent surgery (94[35-141] vs. 63[34-107] minutes, pĀ =Ā 0.071) were comparable. Older age (pĀ <Ā 0.001), SBP <90 (pĀ <Ā 0.001), GCS <9 (pĀ <Ā 0.001), need for emergent operative intervention (pĀ =Ā 0.044), and higher ISS (pĀ <Ā 0.001) were independently associated with mortality. After propensity score matching, mortality was no different between SC and NSC (pĀ =Ā 0.764). CONCLUSIONS: Early morning is a low-volume, high-mortality time for TTAs. Increased mortality at shift change was independently associated with patient/injury factors but not provider/systems factors. Ensuring ample clinical resource allocation during this high acuity time may be prudent to streamline patient care at shift change.


Subject(s)
Trauma Centers , Wounds and Injuries , Humans , Injury Severity Score , Wounds and Injuries/therapy , Retrospective Studies
5.
Hum Mol Genet ; 27(8): 1343-1352, 2018 04 15.
Article in English | MEDLINE | ID: mdl-29432577

ABSTRACT

CHARGE syndrome is an autosomal dominant malformation disorder caused by heterozygous loss of function mutations in the chromatin remodeler CHD7. Chd7 regulates the expression of Sema3a, which also contributes to the pathogenesis of Kallmann syndrome, a heterogeneous condition with the typical features hypogonadotropic hypogonadism and an impaired sense of smell. Both features are common in CHARGE syndrome suggesting that SEMA3A may provide a genetic link between these syndromes. Indeed, we find evidence that SEMA3A plays a role in the pathogenesis of CHARGE syndrome. First, Chd7 is enriched at the Sema3a promotor in neural crest cells and loss of function of Chd7 inhibits Sema3a expression. Second, using a Xenopus CHARGE model, we show that human SEMA3A rescues Chd7 loss of function. Third, to elucidate if SEMA3A mutations in addition to CHD7 mutations also contribute to the severity of the CHARGE phenotype, we screened 31 CHD7-positive patients and identified one patient with a heterozygous non-synonymous SEMA3A variant, c.2002A>G (p.I668V). By analyzing protein expression and processing, we did not observe any differences of the p.I668V variant compared with wild-type SEMA3A, while a pathogenic SEMA3A variant p.R66W recently described in a patient with Kallmann syndrome did affect protein secretion. Furthermore, the p.I668V variant, but not the pathogenic p.R66W variant, rescues Chd7 loss of function in Xenopus, indicating that the p.I668V variant is likely benign. Thus, SEMA3A is part of an epigenetic loop that plays a role in the pathogenesis of CHARGE syndrome, however, it seems not to act as a common direct modifier.


Subject(s)
CHARGE Syndrome/genetics , DNA Helicases/genetics , DNA-Binding Proteins/genetics , Epigenesis, Genetic , Neural Crest/metabolism , Semaphorin-3A/genetics , Animals , CHARGE Syndrome/metabolism , CHARGE Syndrome/pathology , DNA Helicases/metabolism , DNA-Binding Proteins/metabolism , Disease Models, Animal , Embryo, Nonmammalian , Genetic Complementation Test , HEK293 Cells , Homeobox Protein Nkx-2.5/genetics , Homeobox Protein Nkx-2.5/metabolism , Humans , Kallmann Syndrome/genetics , Kallmann Syndrome/metabolism , Kallmann Syndrome/pathology , Mutation , Neural Crest/pathology , Promoter Regions, Genetic , Semaphorin-3A/metabolism , Severity of Illness Index , Xenopus laevis
6.
World J Surg ; 44(11): 3743-3750, 2020 Nov.
Article in English | MEDLINE | ID: mdl-32734451

ABSTRACT

BACKGROUND: Hypocalcemia is cited as a complication of massive transfusion. However, this is not well studied as a primary outcome in trauma patients. Our primary outcome was to determine if transfusion of packed red blood cells (pRBC) was an independent predictor of severe hypocalcemia (ionized calcium ≤ 3.6Ā mg/dL). METHODS: Retrospective, single-center study (01/2004-12/2014) including all trauma patients ≥ 18Ā yo presenting to the ED with an ionized calcium (iCa) level drawn. Variables extracted included demographics, interventions, outcomes, and iCa. Regression models identified independent risk factors for severe hypocalcemia (SH). RESULTS: Seven thousand four hundred and thirty-one included subjects, 716 (9.8%) developed SH within 48Ā h of admission. Median age: 39 (Range: 18-102), systolic blood pressure: 131 (IQR: 114-150), median Glasgow Coma Scale (GCS): 15 (IQR: 10-15), Injury Severity Score (ISS): 14 (IQR: 9-24). SH patients were more likely to have depressed GCS (13 vs 15, p < 0.0001), hypotension (23.2% vs 5.1%, p < 0.0001) and tachycardia (57.0% vs 41.9%, p < 0.0001) compared to non-SH patients. They also had higher emergency operative rate (71.8% vs 29%, p < 0.0001) and higher blood administration prior to minimum iCa [pRBC: (8 vs 0, p < 0.0001), FFP: (4 vs 0, p < 0.0001), platelet: (1 vs 0, p < 0.0001)]. Multivariable analysis revealed penetrating mechanism (AOR: 1.706), increased ISS (AOR: 1.029), and higher pRBC (AOR: 1.343) or FFP administered (AOR: 1.097) were independent predictors of SH. SH was an independent predictor of mortality (AOR: 2.658). Regression analysis identified a significantly higher risk of SH at pRBC + FFP administration of 4Ā units (AOR: 18.706, AUC:. 897 (0.884-0.909). CONCLUSION: Transfusion of pRBC is an independent predictor of SH and is associated with increased mortality. The predicted probability of SH increases as pRBC + FFP administration increases.


Subject(s)
Blood Component Transfusion/adverse effects , Hypocalcemia , Wounds and Injuries , Adolescent , Adult , Aged , Aged, 80 and over , Humans , Hypocalcemia/diagnosis , Hypocalcemia/etiology , Male , Middle Aged , Plasma , Retrospective Studies , Trauma Centers , Wounds and Injuries/complications , Young Adult
7.
Differentiation ; 107: 1-10, 2019.
Article in English | MEDLINE | ID: mdl-30927641

ABSTRACT

Androgen signaling is essential for prostate development, morphogenesis, and regeneration. Emerging evidence also indicates a regulatory role of Notch signaling in prostate development, differentiation, and growth. However, the collaborative regulatory mechanisms of androgen and Notch signaling during prostate development, growth, and regeneration are largely unknown. Hairy and Enhancer of Split 1 (Hes1) is a transcriptional regulator of Notch signaling pathways, and its expression is responsive to Notch signaling. Hes1-expressing cells have been shown to possess the regenerative capability to repopulate a variety of adult tissues. In this study, we developed new mouse models to directly assess the role of the androgen receptor in prostatic Hes1-expressing cells. Selective deletion of AR expression in embryonic Hes1-expressing cells impeded early prostate development both in vivo and in tissue xenograft experiments. Prepubescent deletion of AR expression in Hes1-expressing cells resulted in prostate glands containing abnormalities in cell morphology and gland architecture. A population of castration-resistant Hes1-expressing cells was revealed in the adult prostate, with the ability to repopulate prostate epithelium following androgen supplementation. Deletion of AR in Hes1-expressing cells diminishes their regenerative ability. These lines of evidence demonstrate a critical role for the AR in Notch-responsive cells during the course of prostate development, morphogenesis, and regeneration, and implicate a mechanism underlying interaction between the androgen and Notch signaling pathways in the mouse prostate.


Subject(s)
Prostate/physiology , Receptors, Notch/metabolism , Regeneration , Transcription Factor HES-1 , Androgens/metabolism , Animals , Male , Mice , Models, Animal , Prostate/embryology , Receptors, Androgen/metabolism , Signal Transduction , Transcription Factor HES-1/biosynthesis , Transcription Factor HES-1/genetics
8.
BMC Bioinformatics ; 18(1): 150, 2017 Mar 04.
Article in English | MEDLINE | ID: mdl-28257645

ABSTRACT

BACKGROUND: A family of parsimonious Gaussian mixture models for the biclustering of gene expression data is introduced. Biclustering is accommodated by adopting a mixture of factor analyzers model with a binary, row-stochastic factor loadings matrix. This particular form of factor loadings matrix results in a block-diagonal covariance matrix, which is a useful property in gene expression analyses, specifically in biomarker discovery scenarios where blood can potentially act as a surrogate tissue for other less accessible tissues. Prior knowledge of the factor loadings matrix is useful in this application and is reflected in the one-way supervised nature of the algorithm. Additionally, the factor loadings matrix can be assumed to be constant across all components because of the relationship desired between the various types of tissue samples. Parameter estimates are obtained through a variant of the expectation-maximization algorithm and the best-fitting model is selected using the Bayesian information criterion. The family of models is demonstrated using simulated data and two real microarray data sets. The first real data set is from a rat study that investigated the influence of diabetes on gene expression in different tissues. The second real data set is from a human transcriptomics study that focused on blood and immune tissues. The microarray data sets illustrate the biclustering family's performance in biomarker discovery involving peripheral blood as surrogate biopsy material. RESULTS: The simulation studies indicate that the algorithm identifies the correct biclusters, most optimally when the number of observation clusters is known. Moreover, the biclustering algorithm identified biclusters comprised of biologically meaningful data related to insulin resistance and immune function in the rat and human real data sets, respectively. CONCLUSIONS: Initial results using real data show that this biclustering technique provides a novel approach for biomarker discovery by enabling blood to be used as a surrogate for hard-to-obtain tissues.


Subject(s)
Databases, Genetic , Gene Expression , Supervised Machine Learning , Transcriptome , Animals , Bayes Theorem , Biomarkers/blood , Cluster Analysis , Diabetes Mellitus, Experimental/genetics , Humans , Male , Models, Theoretical , Rats , Rats, Zucker
9.
Transpl Int ; 30(12): 1234-1242, 2017 Dec.
Article in English | MEDLINE | ID: mdl-28777478

ABSTRACT

Calculated panel reactive antibody (cPRA) represents possibility of encountering an incompatible donor for organ transplant candidates and has gradually replaced traditional PRA as a measurement of sensitization level. We tested two cPRA calculation methods on a cohort of renal candidate (n = 613). HLA typing of 563 Chinese deceased renal donors was used to estimate allele and haplotype frequencies of Hong Kong donor pool. The OPTN formula was adopted to generate cPRA (cPRA (freq)). We also incorporated a computer script to compare unacceptable antigens of patients against HLA phenotype of donors. The cPRA based on historical donor filtering was the percentage of filter out count over total number of donors (cPRA (filter)). Values of cPRA (freq) and cPRA (filter) showed almost perfect agreement with Lin's correlation coefficient equal to 1.000. SD of bias was 0.6 cPRA point. Limit of agreement was 0.9 to -1.5 points difference. Furthermore, the poor agreement between our in-house cPRA and values from other online calculators indicated the necessity to use local population data for accurate cPRA calculation. Built-in donor filtering method was more practicable for Hong Kong due to factors such as cost and flexibility. An on-going donor pool can reflect population allele frequencies and permits efficient periodic update of cPRA.


Subject(s)
Donor Selection/methods , HLA Antigens/immunology , Isoantibodies/blood , Kidney Transplantation/mortality , Registries , Tissue and Organ Procurement/methods , Cohort Studies , Female , Graft Rejection , Graft Survival , Histocompatibility Testing/methods , Hong Kong , Humans , Kidney Transplantation/adverse effects , Kidney Transplantation/methods , Male , Retrospective Studies , Risk Assessment , Survival Analysis , Transplantation Immunology
10.
Acta Paediatr ; 106(8): 1239-1245, 2017 Aug.
Article in English | MEDLINE | ID: mdl-28520104

ABSTRACT

Time use could profoundly affect adolescents' health-related quality of life (HRQL). Ideally, overall time use patterns would be considered, because activities within a 24-hour day are inherently correlated (more in one activity means less in another). This review focused on the associations of (i) overall time use patterns and (ii) components of time use patterns with HRQL in adolescents. CONCLUSION: More physical activity, less screen time and more/adequate sleep, in isolation, are associated with better profile-based HRQL subscales. Greater understanding of adolescents' overall time use patterns and HRQL is, therefore, a priority for policy development.


Subject(s)
Adolescent Behavior , Quality of Life , Time Management , Adolescent , Humans
11.
J Pediatr ; 176: 150-5, 2016 09.
Article in English | MEDLINE | ID: mdl-27321065

ABSTRACT

OBJECTIVE: To evaluate whether central adrenal insufficiency (CAI) is present in CHARGE (Coloboma of the eye, Heart defects, Atresia of the choanae, Retardation of growth and/or development, Genital hypoplasia, and Ear abnormalities, including deafness) syndrome, a complex malformation disorder that includes central endocrine dysfunction. STUDY DESIGN: Two cross-sectional studies were performed in Dutch (September 2013-February 2015) and Australian (January 2012-January 2014) CHARGE syndrome clinics. Twenty-seven Dutch and 19 Australian patients (aged 16 months-18 years) with genetically confirmed CHARGE syndrome were included. The low-dose adrenocorticotropin (ACTH) test was used to assess CAI in the Dutch cohort. A peak cortisol response less than 18.1Ā Āµg/dL (500Ā nmol/L) was suspected for CAI, and a glucagon stimulation test was performed for confirmation. Australian patients were screened by single measurements of ACTH and cortisol levels. If adrenal dysfunction was suspected, a standard-dose ACTH test was performed. RESULTS: The low-dose ACTH test was performed in 23 patients (median age 8.4 [1.9-16.9] years). Seven patients showed an insufficient maximum cortisol level (10.3-17.6Ā Āµg/dL, 285-485Ā nmol/L), but CAI was confirmed by glucagon stimulation test in only 1 patient (maximum cortisol level 15.0Ā Āµg/dL, 415Ā nmol/L). In the Australian cohort, 15 patients (median age 9.1 [1.3-17.8] years) were screened, and none had CAI. CONCLUSIONS: CAI was not common in our cohorts, and routine testing of adrenal function in children with CHARGE syndrome is not indicated.


Subject(s)
Adrenal Insufficiency/etiology , CHARGE Syndrome/complications , Adolescent , Adrenal Insufficiency/epidemiology , Child , Child, Preschool , Cross-Sectional Studies , Female , Humans , Infant , Male
12.
Transfusion ; 55(3): 532-43, 2015 Mar.
Article in English | MEDLINE | ID: mdl-25582335

ABSTRACT

BACKGROUND: The Mirasol system has been demonstrated to effectively inactivate white blood cells (WBCs) and reduce pathogens in whole blood in vitro. The purpose of this study was to compare the safety and efficacy of Mirasol-treated fresh whole blood (FWB) to untreated FWB in an in vivo model of surgical bleeding. STUDY DESIGN AND METHODS: A total of 18 anesthetized pigs (40 kg) underwent a 35% total blood volume bleed, cooling to 33Ā°C, and a standardized liver injury. Animals were then randomly assigned to resuscitation with either Mirasol-treated or untreated FWB, and intraoperative blood loss was measured. After abdominal closure, the animals were observed for 14 days, after which the animals were euthanized and tissues were obtained for histopathologic examination. Mortality, tissue near-infrared spectroscopy, red blood cell (RBC) variables, platelets (PLTs), WBCs, and coagulation indices were analyzed. RESULTS: Total intraoperative blood loss was similar in test and control arms (8.3 Ā± 3.2 mL/kg vs. 7.7 Ā± 3.9 mL/kg, p = 0.720). All animals survived to Day 14. Trended values over time did not show significant differences-tissue oxygenation (p = 0.605), hemoglobin (p = 0.461), PLTs (p = 0.807), WBCs (p = 0.435), prothrombin time (p = 0.655), activated partial thromboplastin time (p = 0.416), thromboelastography (TEG)-reaction time (p = 0.265), or TEG-clot formation time (p = 0.081). Histopathology did not show significant differences between arms. CONCLUSIONS: Mirasol-treated FWB did not impact survival, blood loss, tissue oxygen delivery, RBC indices, or coagulation variables in a standardized liver injury model. These data suggest that Mirasol-treated FWB is both safe and efficacious in vivo.


Subject(s)
Blood Safety , Blood Transfusion/methods , Blood/drug effects , Blood/radiation effects , Hemorrhage/therapy , Resuscitation/methods , Riboflavin/pharmacology , Ultraviolet Rays , Animals , Blood Cells/drug effects , Blood Cells/radiation effects , Blood Coagulation Tests , Blood Preservation , Erythrocyte Indices , Female , Hemodilution , Hemorrhage/etiology , Hypothermia, Induced , Lacerations/complications , Lacerations/therapy , Laparotomy , Liver/injuries , Liver/pathology , Male , Random Allocation , Sus scrofa , Swine , Thrombelastography
13.
Eur J Trauma Emerg Surg ; 50(1): 185-195, 2024 Feb.
Article in English | MEDLINE | ID: mdl-37289227

ABSTRACT

PURPOSE: Patients with traumatic brain injury (TBI) are at high risk for venous thromboembolism (VTE). The aim of the present study is to identify factors independently associated with VTE events. Specifically, we hypothesized that the mechanism of penetrating head trauma might be an independent factor associated with increased VTE events when compared with blunt head trauma. METHODS: The ACS-TQIP database (2013-2019) was queried for all patients with isolated severe head injuries (AIS 3-5) who received VTE prophylaxis with either unfractionated heparin or low-molecular-weight heparin. Transfers, patients who died within 72Ā h and those with a hospital length of stay < 48Ā h were excluded. Multivariable analysis was used as the primary analysis to identify independent risk factors for VTE in isolated severe TBI. RESULTS: A total of 75,570 patients were included in the study, 71,593 (94.7%) with blunt and 3977 (5.3%) with penetrating isolated TBI. Penetrating trauma mechanism (OR 1.49, CI 95% 1.26-1.77), increasing age (age 16-45: reference; age > 45-65: OR 1.65, CI 95% 1.48-1.85; age > 65-75: OR 1.71, CI 95% 1.45-2.02; age > 75: OR 1.73, CI 95% 1.44-2.07), male gender (OR 1.53, CI 95% 1.36-1.72), obesity (OR 1.35, CI 95% 1.22-1.51), tachycardia (OR 1.31, CI 95% 1.13-1.51), increasing head AIS (AIS 3: reference; AIS 4: OR 1.52, CI 95% 1.35-1.72; AIS 5: OR 1.76, CI 95% 1.54-2.01), associated moderate injuries (AIS = 2) of the abdomen (OR 1.31, CI 95% 1.04-1.66), spine (OR 1.35, CI 95% 1.19-1.53), upper extremity (OR 1.16, CI 95% 1.02-1.31), lower extremity (OR 1.46, CI 95% 1.26-1.68), craniectomy/craniotomy or ICP monitoring (OR 2.96, CI 95% 2.65-3.31) and pre-existing hypertension (OR 1.18, CI 95% 1.05-1.32) were identified as independent risk factors for VTE complications in isolated severe head injury. Increasing GCS (OR 0.93, CI 95% 0.92-0.94), early VTE prophylaxis (OR 0.48, CI 95% 0.39-0.60) and LMWH compared to heparin (OR 0.74, CI 95% 0.68-0.82) were identified as protective factors for VTE complications. CONCLUSION: The identified factors independently associated with VTE events in isolated severe TBI need to be considered in VTE prevention measures. In penetrating TBI, an even more aggressive VTE prophylaxis management may be justified as compared to that in blunt.


Subject(s)
Brain Injuries, Traumatic , Head Injuries, Closed , Venous Thromboembolism , Humans , Male , Adolescent , Young Adult , Adult , Middle Aged , Heparin/therapeutic use , Heparin, Low-Molecular-Weight/therapeutic use , Venous Thromboembolism/epidemiology , Venous Thromboembolism/etiology , Venous Thromboembolism/prevention & control , Risk Factors , Head Injuries, Closed/complications , Anticoagulants/therapeutic use
14.
Article in English | MEDLINE | ID: mdl-37845367

ABSTRACT

PURPOSE: In general, risk of mortality after trauma correlates with injury severity. Despite arriving in relatively stable clinical condition, however, some patients are at risk of death following mild traumatic brain injury (TBI). The study objective was delineation of patients who die in-hospital following mild isolated TBI in order to inform Emergency Department (ED) disposition and care discussions with patients and families. METHODS: In this retrospective cohort study, patients from the National Trauma Data Bank (NTDB) (2007-2018) were included if they were injured by blunt trauma and sustained a mild TBI (defined as Head Abbreviated Injury Scale [AIS] score of 1 or 2 and arrival Glasgow Coma Scale [GCS] score of 13-15). Exclusions were severe associated injuries (extracranial AIS > 2); transfers; and missing data. Patients were defined by in-hospital mortality: Survivors vs. Mortalities. Demographics, clinical/injury data, and the outcomes were collected and compared with univariate analysis. Multivariate analysis established independent factors associated with in-hospital mortality following mild TBI. RESULTS: In total, 932,107 patients (10% of NTDB population) met study criteria: 928,542 (99.6%) Survivors and 3,565 (0.4%) Mortalities. In general, comorbidities (including home anticoagulation, cardiac disease, and diabetes mellitus) were significantly more common among patients who died (p < 0.001), although drug and alcohol intoxication on arrival were more common among Survivors (16% vs. 7%, p < 0.001; 13% vs. 10%, p < 0.001). In terms of insurance status, Private/Commercial insurance was more common among Survivors (39% vs. 20%, p < 0.001) while Governmental Insurance was more common among Mortalities (55% vs. 36%, p < 0.001). On multivariate analysis, age ≥ 65 was most strongly associated with death (OR 26.43, p < 0.001), followed by ED intubation (OR 10.08, p < 0.001), admission hypotension (OR 4.55, p < 0.001), and comorbidities, particularly end-stage renal disease (ESRD) (OR 3.03, p < 0.001) and immunosuppression (OR 2.18, p < 0.001). CONCLUSIONS: Survivors differed substantially from Mortalities after mild TBI in terms of comorbidities, intoxicants, and insurance status. Independent variables most strongly associated with in-hospital death following mild head injury included age ≥ 65, intubation in the ED, admission hypotension, and comorbidities (particularly ESRD and immunosuppression). Increased clinical vigilance, including a mandatory period of clinical observation, for patients with these risk factors should be considered to optimize outcomes and potentially mitigate death after mild TBI.

15.
Ann Biomed Eng ; 51(9): 2048-2055, 2023 Sep.
Article in English | MEDLINE | ID: mdl-37266719

ABSTRACT

Surgical simulation models have been developed using post-mortem human subjects (PMHS). These models involve the pressurization and ventilation of the PMHS to create a more realistic environment for training and the practice of surgical procedures. The overall objective of this study was to determine the feasibility of a previously developed surgical simulation model to detect soft tissue injuries during a ballistic impact to the torso. One of the main limitations of using PMHS for the assessment of soft tissue injuries in the field of injury biomechanics is the lack of physiological blood flow. To overcome this limitation, the assessment of the surgical simulation model for use in injury biomechanics applications was conducted based on data collected from behind armor blunt trauma (BABT) case studies. Documented injuries in real-world cases included anterior lung contusion, posterior lung contusion, and liver contusion. These real-world injuries were compared to those seen post-impact in the PMHS using pathological and histological techniques. Discussion of limitations and future work is presented.


Subject(s)
Contusions , Soft Tissue Injuries , Humans , Cadaver , Perfusion , Lung , Liver
16.
Am Surg ; 89(10): 4129-4134, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37259503

ABSTRACT

INTRODUCTION: The American College of Surgeons (ACS) delineates trauma team activation (TTA) criteria to identify seriously injured trauma patients in the field. Patients are deemed to be severely undertriaged (SU), placing them at risk for adverse outcomes, when they do not meet TTA criteria but nonetheless sustain significant injuries (Injury Severity Score [ISS] ≥25). OBJECTIVES: Delineate patient demographics, injuries, and outcomes after SU. PARTICIPANTS: Trauma patients presenting to our ACS-verified Level 1 trauma center with ISS ≥25 were included (11/2015-03/2022). Transfers and private vehicle transports were excluded. Patients were dichotomized and compared by trauma arrival level: TTA (Appropriately Triaged, AT) vs routine consults (SU). RESULTS: Study criteria were satisfied by 1653 patients: 1375 (83%) AT and 278 (17%) SU. Severely undertriaged patients were older than AT patients (47 vs 36 years, P < .001). Severely undertriaged occurred almost exclusively following blunt trauma (96% vs 71%, P < .001). Injury Severity Score was lower following SU than AT (29 vs 32, P < .001). The most common severe injuries (Abbreviated Injury Scale score [AIS] ≥3) among the SU group were in the Chest (n = 179, 64%). Severely undertriaged patients necessitated emergent intubation (n = 34, 12%), surgery (n = 59, 21%), and angioembolization (n = 22, 8%) at high rates. Severely undertriaged mortality was n = 40, 14%. CONCLUSION: Severely undertriaged occurred among a substantial proportion of ISS ≥25 patients, predominately following blunt trauma. Severe chest injuries were most likely to evade capture. Rates of intubation, emergent intervention, and in-hospital mortality were high after SU. Efforts should be made to identify such patients in the field as they may benefit from TTA.


Subject(s)
Wounds and Injuries , Wounds, Nonpenetrating , Humans , Retrospective Studies , Triage , Wounds, Nonpenetrating/diagnosis , Wounds, Nonpenetrating/therapy , Injury Severity Score , Abbreviated Injury Scale , Trauma Centers , Wounds and Injuries/diagnosis , Wounds and Injuries/therapy
17.
Am Surg ; 89(4): 743-748, 2023 Apr.
Article in English | MEDLINE | ID: mdl-34399602

ABSTRACT

INTRODUCTION: Most blunt liver injuries are treated with nonoperative management (NOM), and angiointervention (AI) has become a common adjunct. This study evaluated the use of AI, blood product utilization, pharmacological venous thromboembolic prophylaxis (VTEp), and outcomes in severe blunt liver trauma managed nonoperatively at level I versus II trauma centers. METHODS: American College of Surgeons Trauma Quality Improvement Program (TQIP) study (2013-2016), including adult patients with severe blunt liver injuries (AIS score>/= 3) treated with NOM, was conducted. Epidemiological and clinical characteristics, severity of liver injury (AIS), use of AI, blood product utilization, and VTEp were collected. Outcomes included survival, complications, failure of NOM, blood product utilization, and length of stay (LOS). RESULTS: Study included 2825 patients: 2230(78.9%) in level I and 595(21.1%) in level II centers. There was no difference in demographics, clinical presentation, or injury severity between centers. Angiointervention was used in 6.4% in level I and 7.2% in level II centers (P=.452). Level II centers were less likely to use LMWH for VTEp (.003). There was no difference in mortality or failure of NOM. In level II centers, there was a significantly higher 24-hour blood product utilization (PRBC P = .015 and platelets P = .002), longer ventilator days (P = .012), and longer ICU (P< .001) and hospital LOS (P = .024). The incidence of ventilator-associated pneumonia was significantly higher in level II centers (P = .003). CONCLUSION: Utilization of AI and NOM success rates is similar in level I and II centers. However, the early blood utilization, ventilator days, and VAP complications are significantly higher in level II centers.


Subject(s)
Trauma Centers , Wounds, Nonpenetrating , Adult , Humans , Heparin, Low-Molecular-Weight , Treatment Outcome , Injury Severity Score , Retrospective Studies , Wounds, Nonpenetrating/complications , Wounds, Nonpenetrating/therapy , Liver/injuries
18.
Eur J Trauma Emerg Surg ; 49(1): 505-512, 2023 Feb.
Article in English | MEDLINE | ID: mdl-36115907

ABSTRACT

PURPOSE: Severe hepatic injury due to gunshot (GSW) compared to blunt mechanism may have significantly different presentation, management, complications, and outcomes. The aim of this study was to identify the differences. METHODS: Retrospective single-center analysis June 1, 2015-June 30, 2020, included all patients with Grade III-V liver injuries due to GSW or blunt mechanism. Clinical characteristics, severity of injury, liver-related complications (rebleeding, necrosis/abscess, bile leak/biloma, pseudoaneurysm, acute liver failure) and overall outcomes (mortality, hospital length of stay, intensive care unit length of stay, and ventilatory days) were compared. RESULTS: Of 879 patients admitted with hepatic trauma, 347 sustained high-grade injury and were included: 81 (23.3%) due to GSW and 266 (76.7%) due to blunt force. A significantly larger proportion of patients with GSW were managed operatively (82.7 vs. 36.1%, p < 0.001). GSW was associated with significantly more liver-related complications (40.7% vs. 27.4%, p = 0.023), specifically liver necrosis/abscess (18.5% vs. 7.1%, p = 0.003) and bile leak/biloma (12.3% vs. 5.3%, p = 0.028). On subgroup analysis, in patients with grade III injury, the incidence of liver necrosis/abscess and bile leak/biloma remained significantly higher after GSW (13.9% vs. 3.1%, p = 0.008 and 11.1% vs. 2.5%, p = 0.018, respectively). In sub analysis of 88 patients with leading severe liver injuries, GSW had a significantly longer hospital length of stay, ICU length of stay, and ventilator days. CONCLUSION: GSW mechanism to the liver is associated with a higher incidence of liver-related complications than blunt force injury.


Subject(s)
Biliary Tract Diseases , Wounds, Gunshot , Wounds, Nonpenetrating , Humans , Wounds, Gunshot/complications , Wounds, Gunshot/therapy , Wounds, Gunshot/epidemiology , Retrospective Studies , Abscess , Trauma Centers , Injury Severity Score , Liver/injuries , Wounds, Nonpenetrating/complications , Wounds, Nonpenetrating/therapy , Biliary Tract Diseases/complications , Necrosis
19.
Emerg Infect Dis ; 18(10): 1658-61, 2012 Oct.
Article in English | MEDLINE | ID: mdl-23018120

ABSTRACT

More than 900 cases of scarlet fever were recorded in Hong Kong during January-July, 2011. Six cases were complicated by toxic shock syndrome, of which 2 were fatal. Pulsed-field gel electrophoresis patterns suggested a multiclonal epidemic; emm12 was the predominant circulating type. We recommend genetic testing of and antimicrobial resistance monitoring for this reportable disease.


Subject(s)
Epidemics , Scarlet Fever/epidemiology , Streptococcus pyogenes/genetics , Anti-Bacterial Agents/pharmacology , Child , Electrophoresis, Gel, Pulsed-Field , Female , Hong Kong/epidemiology , Humans , Incidence , Microbial Sensitivity Tests , Scarlet Fever/complications , Scarlet Fever/microbiology , Shock, Septic/epidemiology , Shock, Septic/etiology , Streptococcus pyogenes/drug effects
20.
J Trauma Acute Care Surg ; 92(6): 1039-1046, 2022 06 01.
Article in English | MEDLINE | ID: mdl-35081597

ABSTRACT

BACKGROUND: The management of destructive colon injuries requiring resection has shifted from mandatory diverting stoma to liberal use of primary anastomosis. Various risk criteria have been suggested for the selection of patients for primary anastomosis or ostomy. At our center, we have been practicing a policy of liberal primary anastomosis irrespective of risk factors. The purpose of this study was to evaluate the colon-related outcomes in patients managed with this policy. METHODS: This retrospective study included all colon injuries requiring resection. Data collected included patient demographics, injury characteristics, blood transfusions, operative findings, operations performed, complications, and mortality. RESULTS: A total of 287 colon injuries were identified, 101 of whom required resection, forming the study population. The majority (63.4%) were penetrating injuries. Furthermore, 16.8% were hypotensive on admission, 40.6% had moderate or severe fecal spillage, 35.6% received blood transfusion of >4 U, and 41.6% had Injury Severity Score of >15. At index operation, 88% were managed with primary anastomosis and 12% with colon discontinuity, and one patient had stoma. Damage-control laparotomy (DCL) with temporary abdominal closure was performed in 39.6% of patients. Of these patients with DCL, 67.5% underwent primary anastomosis, 30.0% were left with colon discontinuity, and 2.5% had stoma. Overall, after the definitive management of the colon, including those patients who were initially left in colon discontinuity, only six patients (5.9%) had a stoma. The incidence of anastomotic leaks in patients with primary anastomosis at the index operation was 8.0%, and there was no colon-related mortality. The incidence of colon anastomotic leaks in the 27 patients with DCL and primary anastomosis was 11.1%, and there was no colon-related mortality. Multivariate analysis evaluating possible risk factors identified discontinuity of the colon as independent risk factor for mortality. CONCLUSION: Liberal primary anastomosis should be considered in almost all patients with destructive colon injuries requiring resection, irrespective of risk factors. LEVEL OF EVIDENCE: Therapeutic/Care Management; Level IV.


Subject(s)
Abdominal Injuries , Thoracic Injuries , Abdominal Injuries/surgery , Anastomosis, Surgical , Anastomotic Leak , Colon/injuries , Colon/surgery , Colostomy , Humans , Retrospective Studies , Thoracic Injuries/etiology , Treatment Outcome
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